Cambridge University Press (CUP) Acta Medica Okayama 1460-3969 25 2026 Effects of sagging correction calibration error on radiation therapy equipment using image analysis e5 EN Yasushi Fujii Department of Radiology, Chugoku Central Hospital of the Mutual Aid Association of Public School Teachers Takahiro Nakayama Department of Radiology, Chugoku Central Hospital of the Mutual Aid Association of Public School Teachers Junki Oshita Department of Radiology, Chugoku Central Hospital of the Mutual Aid Association of Public School Teachers Ayaka Tsunoda Department of Radiology, Graduate School of Health Sciences, Okayama University Yusuke Saeki Department of Radiological Technology, Kawasaki Medical School Hospital Yoshinori Tanabe Faculty of Medicine, Graduate School of Health Sciences, Okayama University Purpose: This study investigates the effect of sagging correction errors on image quality and geometric coordinate accuracy.<br> Methods: This study utilised the Elekta radiotherapy system, ball bearing (BB), Catphan phantom and MultiMet-WL phantom. Ten distinct flex maps (FMs) were acquired by positioning the BB at the accuracy isocentre and introducing shifts of 0.2, 0.4 and 0.6 mm in the left, table and up directions, respectively. Cone-beam computed tomography images of the Catphan phantom were acquired using 10 FMs. The images were analysed for modulation transfer function (MTF) values and geometric coordinates. Additionally, the Winston–Lutz (W-L) test was conducted under reference couch positions and with a 0.3 mm couch shift.<br> Results: For the Catphan phantom analysis, the standard deviations of MTF10% across FMs were 0.19. The centre-of-gravity coordinates of the insert exhibited shifts of approximately 0.2, 0.4 and 0.6 mm when comparing reference images to those acquired with the shifted FMs. The results of the W-L test with a 0.3 mm couch shift showed radiation isocentre deviations exceeding 1 mm compared to the reference couch positions.<br> Conclusions: Minor sagging correction calibration errors did not remarkably impact image quality; however, they altered the geometric coordinates of the image isocentre. These calibration errors decreased the accuracy of off-isocentre positioning. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0969-806X 237 2025 Impact of different X-ray tube positions on actual dose measurements during CT examinations -An effect of patient physique- 113001 EN Hiroaki Hayashi College of Transdisciplinary Sciences for Innovation, Kanazawa University Tatsuya Maeda Graduate School of Medical Sciences, Kanazawa University Kazuki Takegami Department of Radiological Technology, Yamaguchi University Hospital Sota Goto Faculty of Health Sciences, Kobe Tokiwa University Takashi Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University Natsumi Kimoto Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University Rina Nishigami Graduate School of Medical Sciences, Kanazawa University Daiki Kobayashi Graduate School of Medical Sciences, Kanazawa University Yuki Kanazawa Faculty of Life Science, Kumamoto University Kazuta Yamashita Department of Orthopedics, School of Medicine, Tokushima University Takeshi Konishi MEDITEC JAPAN Co., Ltd. Motochika Maki MEDITEC JAPAN Co., Ltd. Dose management of patients is very important during X-ray Computed Tomography (CT) examinations, but because the patient's surface dose is inhomogeneous, it is difficult to measure the most probable value using a small passive-type dosimeter, lent to the patient. To solve this problem, our research group developed a precise dose analysis procedure in which a systematic uncertainty related to the X-ray incident direction (θin) is reduced. θin information was analyzed from CT images. However, the applicability of our procedure to actual patients with various physiques has not been examined. This study aims to propose a dose analysis procedure that can be applied to patients with various physiques, and to show its impact on dose measurement. Clinical data of 198 patients with Body Mass Index (BMI) values between 15 and 40 kg/m2 (mean value: 23.1 ± 3.8 kg/m2) who underwent chest CT scans were analyzed after dividing them into three groups based on BMI values. The absorbed dose was measured with a small-type Optically Stimulated Luminescence (OSL) dosimeter. To derive correction factors related to θin, the dependence of the actually-measured dose values of various patients on θin was analyzed. The correction coefficients were determined independently for the three groups classified by BMI values. By correcting the effect of θin, the systematic uncertainty element could be reduced, resulting in 30 % reduction of the uncertainty. Furthermore, it was found that our analysis procedure makes it possible to visualize outliers. In comparison with the expected dose values based on Computed Tomography Dose Index (CTDI) values, most of the data fell within the range of ±1.34 mGy (=1σ). However, 7 % of the data showed large deviations larger than 2σ. In conclusion, our research group has developed a procedure for measuring patient surface doses that can be applied to patients having various physiques, in which the effects of X-ray incident direction were accurately corrected. The procedure could be one solution to the problems with actual dose measurements during CT examinations, and will be useful for dose management based on the small-type dosimeter. No potential conflict of interest relevant to this article was reported.

Japan Society of Mechanical Engineers Acta Medica Okayama 1880-5566 20 2 2025 DNS analysis on the correlation between local burning velocity and flame displacement speed of turbulent premixed flames 25-00212 EN Kazuya TSUBOI Faculty of Environmental, Life, Natural Science and Technology, Okayama University The local burning velocity and flame displacement speed are the major properties of premixed flames. The local burning velocity, which is the instantaneous quantity based on the local consumption rate of the unburnt mixture, is considered to be the most appropriate burning velocity in terms of the definition. The local burning velocity can be evaluated theoretically and numerically; however, it is almost impossible to obtain it experimentally using the current technology of measurement. The flame displacement speed can be evaluated more easily than the local burning velocity and compared with the flame displacement speed obtained from experiments. However, the local burning velocity and flame displacement speed have been discussed separately in turbulent premixed flames. In this study, to clarify the relation between the local burning velocity and the flame displacement speed, numerical analyses were performed using the DNS database of statistically steady and fully developed turbulent premixed flames with different density ratios of the unburnt mixture to the burnt product and with different Lewis numbers. It was found that for different density ratios, the local burning velocity was little sensitive to the flame displacement speed in any case under the unity Lewis number. This means the correlation between the local burning velocity and the flame displacement speed is little affected by the dilation of a flame. For different Lewis numbers, the correlation between the local burning velocity and the flame displacement speed was negative in Le = 0.8, and positive in Le = 1.2. This can be explained by the effect of the Lewis number on the local burning velocity, and the flame displacement speed was little affected by the Lewis number in the correlation between the local burning velocity and the flame displacement speed. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2073-4344 15 2 2025 Palladium-Catalyzed Decarbonylative Nucleophilic Halogenation of Acid Anhydrides 191 EN Tian Tian Graduate School of Natural Science and Technology, Okayama University Shuhei Uei Department of Chemistry, Faculty of Science, Okayama University Weidan Yan Graduate School of Natural Science and Technology, Okayama University Yasushi Nishihara Research Institute for Interdisciplinary Science (RIIS), Okayama University In this study, we developed a palladium-catalyzed decarbonylative nucleophilic halogenation reaction using inexpensive and readily available acid anhydrides as substrates. This approach effectively circumvents the instability of acyl chlorides and the low reactivity of acyl fluorides. The Pd/Xantphos catalyst system exhibited excellent compatibility with the thermodynamically and kinetically challenging reductive elimination of C–X bonds (X = I, Br, and Cl) from Pd(II) intermediates. Notably, for electron-donating substrates, adopting an open system significantly improved the reaction efficiency. The positive effect of the open system may be due to the reversible nature of CO insertion and deinsertion, which helps direct the reaction toward the desired pathway by allowing the generated CO to exit the reaction system. Mechanistic studies suggest that the reaction proceeds through a highly reactive acyl halide intermediate, followed by a unimolecular fragment coupling (UFC) pathway via decarbonylation or an alternative pathway involving the formation of an activated anionic palladate complex in the presence of lithium halide. No potential conflict of interest relevant to this article was reported.

Japanese Society of Radiological Technology Acta Medica Okayama 0369-4305 82 2 2026 放射線治療装置の回転座標系誤差が軸外targetの照射精度に及ぼす影響とTG142のトレランスの評価 26-1566 EN Takahiro Nakayama Department of Radiology, Public Mutual Aid Association Chugoku Central Hospital Yoshinori Tanabe Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Yasushi Fujii Department of Radiology, Public Mutual Aid Association Chugoku Central Hospital 【目的】放射線治療装置の回転座標系の誤差が軸外targetの照射精度に及ぼす影響を定量的に評価し，TG142における回転座標系誤差（±1.0°）のトレランスの妥当性を検討する．【方法】Elekta社製放射線治療装置（Elekta, Stockholm, Sweden）とMultiMet-WL QAファントム（Sun Nuclear, Melbourne, FL, USA）を用いて，6個のtargetに対してoff isocenterのWinston–Lutz test（WL test）を実施した．Baselineの測定に加え，意図的にcollimator，gantry，couchに+0.5°, +1.0°回転誤差を加えた6条件で測定を行い，照射野中心とtarget中心のベクトル距離（S値）および各方向（gantry-target: GT, left-right: LR, anterior-posterior: AP）の位置ずれを解析した．【結果】Isocenterからの距離が大きいtargetほど位置ずれが顕著であった．特にcollimator回転誤差の影響が最も大きく，isocenterから7 cm離れたtargetでは0.5°の回転誤差でもS値が最大1.24 mmに達した．次に影響が大きかったのはcouch回転であり，gantry回転はtargetの配置が回転軸に近いものが多く相対的に影響が少なかった．回転座標系の誤差は幾何学的誤差の影響が強く，位置ずれに方向依存性があった．【結語】Collimatorやcouchの影響が大きく，0.5°の誤差でも1 mm以上の位置ずれが生じることがあった．Gantryの影響はtargetの配置依存があり，相対的に小さかった．軸外targetの照射において，TG142の±1.0°のトレランスは放射線治療装置の種類にかかわらず最低限遵守するべき基準であり，targetの配置次第では臨床的に十分なマージンを保証できない可能性が示された．Target配置に応じたより厳格な基準と定期的quality assurance（QA）の重要性が示唆された． No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2196-2995 12 1 2025 Natural Effects and Separable Effects: Insights into Mediation Analysis 20 EN Etsuji Suzuki Department of Epidemiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Shinozaki Interfaculty Initiative in Information Studies, the University of Tokyo Eiji Yamamoto Okayama University of Science Purpose of Review We compare natural effects and separable effects under nonparametric structural equation models with independent errors, highlighting their similarities and differences. By examining their required properties and sufficient conditions for identification, we aim to provide deeper insights into mediation analysis.<br> Recent Findings If certain assumptions about confounding, positivity, and consistency are met, we can identify natural direct and indirect effects under nonparametric structural equation models with independent errors. However, these effects have been criticized because they rely on a specific cross-world quantity, and the so-called cross-world independence assumption cannot be empirically verified. Furthermore, interventions on the mediator may sometimes be challenging to even conceive. As an alternative approach, separable effects have recently been proposed and applied in mediation analysis, often under finest fully randomized causally interpretable structured tree graph models. These effects are defined without relying on any cross-world quantities and are claimed to be identifiable under assumptions that are testable in principle, thereby addressing some of the challenges associated with natural direct and indirect effects.<br> Summary To conduct meaningful mediation analysis, it is crucial to clearly define the research question of interest, and the choice of methods should align with the nature of the question and the assumptions researchers are willing to make. Examining the underlying philosophical perspectives on causation and manipulation can provide valuable insights. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Advantages of Single-Position Surgery over Posterior Fusion for Single-Level Degenerative Lumbar Diseases 359 368 EN Tomohiko Hirose Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital Hisanori Ikuma Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital Kazutoshi Otsuka Otsuka Orthopedic Clinic Keisuke Kawasaki Department of Orthopedic Surgery, Kagawa Prefectural Central Hospital Original Article 10.18926/AMO/69437 Single-position surgery with lateral lumbar interbody fusion (LLIF) and percutaneous pedicle screws (PPSs) is gaining attention for its reduced invasiveness. We developed SPAPS, a technique allowing two surgeons to perform anterior LLIF and posterior PPS insertion simultaneously in a single lateral decubitus position. This retrospective study compared SPAPS (SPAPS-LLIF, Group SL) and minimally invasive posterior/transforaminal lumbar interbody fusion (MIS-PLIF/TLIF, Group PT) in patients treated between 2016 and 2019 with a two-year follow-up. Operative time, estimated blood loss (EBL), length of hospital stay (LOS), JOABPEQ and VAS scores, segmental lordotic angle, lumbar lordotic angle, segmental Cobb’s angle, PPS misplacement, PPS loosening, fusion status, and muscle cross-sectional areas were compared. Fifty-two patients were analyzed (Group SL: 25; Group PT: 27). SPAPS significantly reduced operative time (118.0 vs. 165.3 min, p <0.01) and estimated blood loss (8.6 vs. 164.1 mL, p<0.01). While clinical outcomes and hospital stay were comparable, Group SL had significantly lower PPS loosening (0% vs. 13%, p<0.01) and non-union rates (0% vs. 22.2%, p=0.02). Multifidus muscle atrophy was also less in Group SL (−14.3 vs. −121.5 mm2, p<0.01). SPAPS demonstrated advantages in reducing surgical invasiveness without compromising clinical efficacy, offering a promising alternative to conventional posterior fusion surgery. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 4 2025 Femoral and Global Femoral Offset, but not Anteroposterior Offset, to Improve Postoperative Outcomes Following Total Hip Arthroplasty: Considerations Independent of the Contralateral Side 269 278 EN Norio Imai Division of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences Yuki Hirano Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Daisuke Homma Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Yuki Endo Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Yoji Horigome Division of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences Hayato Suzuki Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Hiroyuki Kawashima Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Original Article 10.18926/AMO/69152 The global femoral offset (the sum of the acetabular and femoral offsets) influences outcomes after total hip arthroplasty (THA). The optimal offset using plain radiographs has been reported, but internal and external rotations of the hip affect the offset value, producing unclear results when the nonsurgical side is not intact. We investigated the relationship between a functional hip score, i.e., the Harris Hip Score (HHS) and its effect on the post-THA anteroposterior and lateral offsets, and we sought to identify the optimal offset value. The cases of 158 patients with hemilateral hip osteoarthritis who underwent THA at a single center were retrospectively analyzed in this cross-sectional study. Three-dimensional pelvic and femoral models generated from computed tomography were used to examine several parameters, and the results revealed a significant binomial correlation among the modified HHS and femoral and global femoral offsets, with maximum values of 21.3 mm and 40 mm/100 cm body height, respectively. Pelvic and femoral parameters were measured and evaluated via alignment with a specific coordinate system. Our findings indicate that preoperative planning using these parameters may improve postoperative hip function, even when the nonoperative side is unsuitable for use as a reference, as in bilateral hip osteoarthritis cases. No potential conflict of interest relevant to this article was reported.

S. Karger AG Acta Medica Okayama 0250-8095 2025 Supplement-induced acute kidney injury reproduced in kidney organoids EN Hiroyuki Nakanoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Fukushima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Soichiro Haraguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kitamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Introduction: Acute kidney injury associated with the consumption of Beni-koji CholesteHelp supplements, which contain red yeast rice (Beni-Koji), has become a significant public health concern in Japan. While renal biopsy findings from several case reports have suggested tubular damage, no definitive causal relationship has been established, and the underlying mechanisms of kidney injury remain poorly understood. The complexity of identifying toxic substances in supplements containing various bioactive compounds makes conventional investigative approaches both time-consuming and challenging. This highlights an urgent need to establish a reliable platform for assessing organ-specific toxicity in such supplements. In this study, we utilized a kidney organoid model derived from adult rat kidney stem cells (KS cells) to assess the potential tubular toxicity of these supplements. Methods: KS cell clusters were cultured in three-dimensional system supplemented with growth factors to promote kidney organoids. The organoids were subsequently exposed to Beni-koji CholesteHelp supplements or cisplatin, followed by histological and molecular analyses to evaluate structural impacts. Results: Established organoids had the kidney-like structures including tubular-like structures and glomerulus-like structures at the tips of multiple tubules. Treatment with Beni-koji CholesteHelp supplements induced significant tubular damage in the organoids, characterized by epithelial cell thinning, structural disruption, and increase in cleaved-caspase 3-positive apoptotic tubular cells, similar to the organoids treated with cisplatin. Conclusion: These findings provide the first evidence suggesting that certain toxicants in specific batches of Beni-koji CholesteHelp supplements cause direct renal tubular injury. This KS cell-based organoid system represents a cost-effective, reproducible, and technically simple platform for nephrotoxicity screening. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 0340-7004 74 3 2025 Cancer-associated fibroblasts promote pro-tumor functions of neutrophils in pancreatic cancer via IL-8: potential suppression by pirfenidone 96 EN Tomohiko Yagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Nogi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsuki Taniguchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Yoshimoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kanto Suemori Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuo Nagai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuto Fujita Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fuminori Teraishi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Ohara Departments of Pathology and Experimental Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background The mechanisms by which neutrophils acquire pro-tumor properties remain poorly understood. In pancreatic cancer, cancer-associated fibroblasts (CAFs) may interact with neutrophils, directing them to promote tumor progression.<br> Methods To validate the association between CAFs and neutrophils, the localization of neutrophils was examined in clinically resected pancreatic cancer specimens. CAFs were produced by culturing in cancer-conditioned media, and the effects of these CAFs on neutrophils were examined. In vitro migration and invasion assays assess the effect of CAF-activated neutrophils on cancer cells. The factors secreted by the activated neutrophils were also explored. Finally, pirfenidone (PFD) was tested to determine whether it could suppress the pro-tumor functions of activated neutrophils.<br> Results In pancreatic cancer specimens, neutrophils tended to co-localize with IL-6-positive CAFs. Neutrophils co-cultured with CAFs increased migratory capacity and prolonged life span. CAF-affected neutrophils enhance the migratory and invasive activities of pancreatic cancer cells. IL-8 is the most upregulated cytokine secreted by the neutrophils. PFD suppresses IL-8 secretion from CAF-stimulated neutrophils and mitigates the malignant traits of pancreatic cancer cells.<br> Conclusion CAFs activate neutrophils and enhance the malignant phenotype of pancreatic cancer. The interactions between cancer cells, CAFs, and neutrophils can be disrupted by PFD, highlighting a potential therapeutic approach. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1472-6831 24 1 2024 Histological differences related to autophagy in the minor salivary gland between primary and secondary types of Sjögren's syndrome 1099 EN Hitomi Ono-Minagi Department of Cytology and Histology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Tsutomu Nohno Department of Cytology and Histology, Okayama University Medical School Kiyofumi Takabatake Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takehiro Tanaka Department of Pathology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takayuki Katsuyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Hospital Kohta Miyawaki Division of Precision Medicine, Kyushu University School of Medicine Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Seiji Iida Department of Oral and Maxillofacial Reconstructive Surgery, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yoshino Department of Pathology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takayoshi Sakai Department of Rehabilitation for Orofacial Disorders, Osaka University Graduate School of Dentistry Hideyo Ohuchi Department of Cytology and Histology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Some forms of Sjögren’s syndrome (SS) follow a clinical course accompanied by systemic symptoms caused by lymphocyte infiltration and proliferation in the liver, kidneys, and other organs. To better understand the clinical outcomes of SS, here we used minor salivary gland tissues from patients and examine their molecular, biological, and pathological characteristics. A retrospective study was performed, combining clinical data and formalin-fixed paraffin-embedded (FFPE) samples from female patients over 60 years of age who underwent biopsies at Okayama University Hospital. We employed direct digital RNA counting with nCounter® and multiplex immunofluorescence analysis with a PhenoCycler™ on the labial gland biopsies. We compared FFPE samples from SS patients who presented with other connective tissue diseases (secondary SS) with those from stable SS patients with symptoms restricted to the exocrine glands (primary SS). Secondary SS tissues showed enhanced epithelial damage and lymphocytic infiltration accompanied by elevated expression of autophagy marker genes in the immune cells of the labial glands. The close intercellular distance between helper T cells and B cells positive for autophagy-associated molecules suggests accelerated autophagy in these lymphocytes and potential B cell activation by helper T cells. These findings indicate that examination of FFPE samples from labial gland biopsies can be an effective tool for evaluating molecular histological differences between secondary and primary SS through multiplexed analysis of gene expression and tissue imaging. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2073-4409 13 10 2024 Exploring the Regulators of Keratinization: Role of BMP-2 in Oral Mucosa 807 EN Xindi Mu Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuaki Ono Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ha Thi Thu Nguyen Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ziyi Wang Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kun Zhao Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Taishi Komori Tomoko Yonezawa Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuo Kuboki Department of Oral Rehabilitation and Implantology, Okayama University Hospital Toshitaka Oohashi Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The oral mucosa functions as a physico-chemical and immune barrier to external stimuli, and an adequate width of the keratinized mucosa around the teeth or implants is crucial to maintaining them in a healthy and stable condition. In this study, for the first time, bulk RNA-seq analysis was performed to explore the gene expression of laser microdissected epithelium and lamina propria from mice, aiming to investigate the differences between keratinized and non-keratinized oral mucosa. Based on the differentially expressed genes (DEGs) and Gene Ontology (GO) Enrichment Analysis, bone morphogenetic protein 2 (BMP-2) was identified to be a potential regulator of oral mucosal keratinization. Monoculture and epithelial-mesenchymal cell co-culture models in the air-liquid interface (ALI) indicated that BMP-2 has direct and positive effects on epithelial keratinization and proliferation. We further performed bulk RNA-seq of the ALI monoculture stimulated with BMP-2 in an attempt to identify the downstream factors promoting epithelial keratinization and proliferation. Analysis of the DEGs identified, among others, IGF2, ID1, LTBP1, LOX, SERPINE1, IL24, and MMP1 as key factors. In summary, these results revealed the involvement of a well-known growth factor responsible for bone development, BMP-2, in the mechanism of oral mucosal keratinization and proliferation, and pointed out the possible downstream genes involved in this mechanism. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0340-7004 72 11 2023 PD-L1-expressing cancer-associated fibroblasts induce tumor immunosuppression and contribute to poor clinical outcome in esophageal cancer 3787 3802 EN Kento Kawasaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Kato Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Ohara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasushige Takeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hijiri Matsumoto Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seitaro Nishimura Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomoyoshi Kunitomo Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masaaki Akai Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Teruki Kobayashi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriyuki Nishiwaki Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hajime Kashima Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoaki Maeda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tazawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Shirakawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The programmed cell death 1 protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays a crucial role in tumor immunosuppression, while the cancer-associated fibroblasts (CAFs) have various tumor-promoting functions. To determine the advantage of immunotherapy, the relationship between the cancer cells and the CAFs was evaluated in terms of the PD-1/PD-L1 axis. Overall, 140 cases of esophageal cancer underwent an immunohistochemical analysis of the PD-L1 expression and its association with the expression of the α smooth muscle actin, fibroblast activation protein, CD8, and forkhead box P3 (FoxP3) positive cells. The relationship between the cancer cells and the CAFs was evaluated in vitro, and the effect of the anti-PD-L1 antibody was evaluated using a syngeneic mouse model. A survival analysis showed that the PD-L1+ CAF group had worse survival than the PD-L1- group. In vitro and in vivo, direct interaction between the cancer cells and the CAFs showed a mutually upregulated PD-L1 expression. In vivo, the anti-PD-L1 antibody increased the number of dead CAFs and cancer cells, resulting in increased CD8+ T cells and decreased FoxP3+ regulatory T cells. We demonstrated that the PD-L1-expressing CAFs lead to poor outcomes in patients with esophageal cancer. The cancer cells and the CAFs mutually enhanced the PD-L1 expression and induced tumor immunosuppression. Therefore, the PD-L1-expressing CAFs may be good targets for cancer therapy, inhibiting tumor progression and improving host tumor immunity. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 Evaluation of the Efficacy and Safety of Tenofovir Disoproxil Fumarate in Intercepting Mother-to-Child Transmission of Hepatitis B Virus 107 113 EN Dongxiang Han Department of Obstetrics, Shijiazhuang Maternity & Child Healthcare Hospital Jianxiu Du Department of Laboratory Medicine, Shijiazhuang Maternity & Child Healthcare Hospital Wei Wang Department of Obstetrics, Shijiazhuang Maternity & Child Healthcare Hospital Cui Wang Department of Functional, Shijiazhuang Maternity & Child Healthcare Hospital Original Article 10.18926/AMO/66913 Vertical transmission of hepatitis B virus (HBV), especially in Asia, is a key target in the global elimination of HBV. This study assessed the effects of tenofovir disoproxil fumarate (TDF) in pregnant women for mother-to-infant transmission of HBV. A total of 122 pregnant women at our hospital met the inclusion criteria for high HBV DNA viral loads. They were randomly divided into TDF-treatment (n=70) and placebo (n=52) groups. Maternal liver function and serum HBV DNA load were tested before and after treatment. Clinical and laboratory data of infants were assayed at delivery and 7-months post-partum visit and compared between the two groups. There was no difference in clinical characteristics of participants between the two groups. There were no significant differences in liver function markers, including alanine aminotransferase, total bilirubin, blood creatinine, and blood urea nitrogen levels before and after TDF treatment. The serum HBV DNA viral load of the TDF-treated group became significantly lower than those of the control group and their own pre-medication levels. Infants showed no significant difference in body growth, including weight, height, head size, and five-min Apgar score. At 7 months after birth, 94.29% of infants in the TDF group and 86.54% of control-group infants had protective HBsAb levels ≥ 10 mIU/ml (p>0.05). The HBV infection rate of infants in the TDF-treated group was lower than that in the non-treated group. In high-HBV-DNA-load pregnant women, TDF administered from 28 weeks gestational age to delivery was associated with a lower risk of mother-to-infant transmission of HBV. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2662-4729 47 2 2024 Evaluation of the effect of sagging correction calibration errors in radiotherapy software on image matching 589 596 EN Yumi Yamazawa Department of Radiology, Niigata Prefectural Central Hospital Akitane Osaka Department of Radiology, Niigata Prefectural Central Hospital Yasushi Fujii Department of Radiology, Chugoku Central Hospital of the Mutual Aid Association of Public School Teachers Takahiro Nakayama Department of Radiology, Chugoku Central Hospital of the Mutual Aid Association of Public School Teachers Kunio Nishioka Department of Radiology, Tokuyama Central Hospital Yoshinori Tanabe Faculty of Medicine, Graduate School of Health Sciences, Okayama University To investigate the impact of sagging correction calibration errors in radiotherapy software on image matching. Three software applications were used, with and without a polymethyl methacrylate rod supporting the ball bearings (BB). The calibration error for sagging correction across nine flex maps (FMs) was determined by shifting the BB positions along the Left–Right (LR), Gun–Target (GT), and Up–Down (UD) directions from the reference point. Lucy and pelvic phantom cone-beam computed tomography (CBCT) images underwent auto-matching after modifying each FM. Image deformation was assessed in orthogonal CBCT planes, and the correlations among BB shift magnitude, deformation vector value, and differences in auto-matching were analyzed. The average difference in analysis results among the three softwares for the Winston–Lutz test was within 0.1 mm. The determination coefficients (R2) between the BB shift amount and Lucy phantom matching error in each FM were 0.99, 0.99, and 1.00 in the LR-, GT-, and UD-directions, respectively. The pelvis phantom demonstrated no cross-correlation in the GT direction during auto-matching error evaluation using each FM. The correlation coefficient (r) between the BB shift and the deformation vector value was 0.95 on average for all image planes. Slight differences were observed among software in the evaluation of the Winston–Lutz test. The sagging correction calibration error in the radiotherapy imaging system was caused by an auto-matching error of the phantom and deformation of CBCT images. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 6 2022 Serum miR-377 Can Be Used as a Diagnostic Marker for Acute Coronary Syndrome and Can Regulate Proinflammatory Factors and Endothelial Injury Markers 723 730 EN Quan Zhang Department of Cardiovascular Medicine, Affiliated Hospital of Gansu Medical College Lixia Yang Department of Cardiovascular Medicine, Affiliated Hospital of Gansu Medical College Guozhen Wan Department of Cardiovascular Medicine, Affiliated Hospital of Gansu Medical College Xiaoqiang Zhang Department of Cardiovascular Medicine, Affiliated Hospital of Gansu Medical College Ying Wang Department of Cardiovascular Medicine, Affiliated Hospital of Gansu Medical College Guannan Zhao Department of Dermatological, Pingliang Traditional Chinese Medicine Hospital Original Article 10.18926/AMO/64123 The diagnostic value of microRNA-377 (miR-377) in patients with acute coronary syndrome (ACS) and explored miR-377’s potential mechanisms. We performed an qRT-PCR to assess serum miR-377 levels in ACS patients and coronary artery ligation rat models. The diagnostic value of miR-377 was evaluated by determining the ROC curve. An ELISA assay was conducted to detect the model rat endothelial damage markers von Willebrand factor (vWF) and heart-type fatty acid binding protein (H-FABP), and proinflammatory cytokines TNF-α, IL-6, and IL-1β. The serum miR-377 level was elevated in the ACS patients and significantly increased in the ACS rats. MiR-377 has a high diagnostic value in ACS patients, with a 0.844 ROC, 76.47% specificity, and 87.10% sensitivity. MiR-377 was positively correlated with the expressions of vWF, H-FABP, cTnI, TNF-α, IL-6, and IL-1β. In ACS rats, reducing the expression of miR-377 significantly inhibited the increases in vWF, H-FABP, TNF-α, IL-6, and IL-1β. An elevated miR-377 level can be used as a diagnostic marker in patients with ACS. A reduction of miR-377 may alleviate ACS by improving myocardial damage such as endothelial injury and the inflammatory response. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 76 5 2022 Current Insights into Mesenchymal Signatures in Glioblastoma 489 502 EN Yuji Matsumoto Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomotsugu Ichikawa Department of Neurological Surgery, Kagawa Prefectural Central Hospital Kazuhiko Kurozumi Department of Neurosurgery, Hamamatsu University Hospital Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Review 10.18926/AMO/64024 Glioblastoma (GBM) is a fatal primary malignant brain tumor in adults. Despite decades of research, the prognosis for GBM patients is still disappointing. One major reason for the intense therapeutic resistance of GBM is inter- and intra-tumor heterogeneity. GBM-intrinsic transcriptional profiling has suggested the presence of at least three subtypes of GBM: the proneural, classic, and mesenchymal subtypes. The mesenchymal subtype is the most aggressive, and patients with the mesenchymal subtype of primary and recurrent tumors tend to have a worse prognosis compared with patients with the other subtypes. Furthermore, GBM can shift from other subtypes to the mesenchymal subtype over the course of disease progression or recurrence. This phenotypic transition is driven by diverse tumor-intrinsic molecular mechanisms or microenvironmental factors. Thus, better understanding of the plastic nature of mesenchymal transition in GBM is pivotal to developing new therapeutic strategies. In this review, we provide a comprehensive overview of the current understanding of the elements involved in the mesenchymal transition of GBM and discuss future perspectives. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 2046-2069 12 22 2022 Droplet motion on a wrinkled PDMS surface with a gradient structural length scale shorter than the droplet diameter 13917 EN Yutaka Yamada Graduate School of Natural Science and Technology, Okayama University Kazuma Isobe Graduate School of Natural Science and Technology, Okayama University Akihiko Horibe Graduate School of Natural Science and Technology, Okayama University Droplet transportation using a wettability gradient surface has attracted much attention owing to applications such as in microfluidic devices. A surface with a spatial structural gradient was prepared through a simple and cost-effective process even though understanding of droplet behavior on the structure was still limited. Here, we report impinging droplet motion on a gradient wrinkled surface. Surfaces were prepared through hard film deposition on soft pre-strained polydimethylsiloxane (PDMS) with a mask installed with a slit to control the amount of deposition, which is related to the wavelength of the wrinkles. Droplets were impinged with varying position with respect to the structure, and the droplet motion was observed in the direction away from the region under the slit. We found an asymmetric contact angle and alternate motion on both sides of the three-phase contact line during the motion according to the gradient of the wrinkle wavelength. These results may help not only to understand the behavior of droplet impingement on a gradient structural surface but also to further develop applications using directional droplet transfer. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1996-1944 14 12 2021 Biological Effects of Bioresorbable Materials in Alveolar Ridge Augmentation: Comparison of Early and Slow Resorbing Osteosynthesis Materials 3286 EN Hotaka Kawai Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shintaro Sukegawa Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keisuke Nakano Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kiyofumi Takabatake Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Sawako Ono Department of Pathology, Kagawa Prefectural Central Hospital Hitoshi Nagatsuka Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshihiko Furuki Department of Oral and Maxillofacial Surgery, Kagawa Prefectural Central Hospital The purpose of this study was to investigate the bone healing properties and histological environment of a u-HA/PLLA/PGA (u-HA-uncalcined and unsintered hydroxyapatite, PLLA-Poly L-lactic acid, PGA-polyglycolic acid) composite device in humans, and to understand the histological dynamics of using this device for maxillofacial treatments. Twenty-one subjects underwent pre-implant maxillary alveolar ridge augmentation with mandibular cortical bone blocks using u-HA/PLLA or u-HA/PLLA/PGA screws for fixation. Six months later, specimens of these screws and their adjacent tissue were retrieved. A histological and immunohistochemical evaluation of these samples was performed using collagen 1a, ALP (alkaline phosphatase), and osteocalcin. We observed that alveolar bone augmentation was successful for all of the subjects. Upon histological evaluation, the u-HA/PLLA screws had merged with the bone components, and the bone was directly connected to the biomaterial. In contrast, direct bone connection was not observed for the u-HA/PLLA/PGA screw. Immunohistological findings showed that in the u-HA/PLLA group, collagen 1a was positive for fibers that penetrated vertically into the bone. Alkaline phosphatase was positive only in the u-HA/PLLA stroma, and the stroma was negative for osteocalcin. In this study, u-HA/PLLA showed a greater bioactive bone conductivity than u-HA/PLLA/PGA and a higher biocompatibility for direct bone attachment. Furthermore, u-HA/PLLA was shown to have the potential for bone formation in the stroma. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 2021 VEGFR2 blockade augments the effects of tyrosine kinase inhibitors by inhibiting angiogenesis and oncogenic signaling in oncogene-driven non-small-cell lung cancers EN Hiromi Watanabe Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Eiki Ichihara Department of Allergy and Respiratory Medicine, Okayama University Hospital Hiroe Kayatani Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Go Makimoto Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kiichiro Ninomiya Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuya Nishii Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hisao Higo Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Chihiro Ando Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Sachi Okawa Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takamasa Nakasuka Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hirohisa Kano Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Naofumi Hara Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Atsuko Hirabae Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuka Kato Center for Innovative Clinical Medicine, Okayama University Hospital Takashi Ninomiya Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshio Kubo Center for Clinical Oncology, Okayama University Hospital Kammei Rai Department of Allergy and Respiratory Medicine, Okayama University Hospital Kadoaki Ohashi Department of Allergy and Respiratory Medicine, Okayama University Hospital Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital Masahiro Tabata Center for Clinical Oncology, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Katsuyuki Kiura Department of Allergy and Respiratory Medicine, Okayama University Hospital Molecular agents targeting the epidermal growth factor receptor (EGFR)-, anaplastic lymphoma kinase (ALK)- or c-ros oncogene 1 (ROS1) alterations have revolutionized the treatment of oncogene-driven non-small-cell lung cancer (NSCLC). However, the emergence of acquired resistance remains a significant challenge, limiting the wider clinical success of these molecular targeted therapies. In this study, we investigated the efficacy of various molecular targeted agents, including erlotinib, alectinib, and crizotinib, combined with anti-vascular endothelial growth factor receptor (VEGFR) 2 therapy. The combination of VEGFR2 blockade with molecular targeted agents enhanced the anti-tumor effects of these agents in xenograft mouse models of EGFR-, ALK-, or ROS1-altered NSCLC. The numbers of CD31-positive blood vessels were significantly lower in the tumors of mice treated with an anti-VEGFR2 antibody combined with molecular targeted agents compared with in those of mice treated with molecular targeted agents alone, implying the antiangiogenic effects of VEGFR2 blockade. Additionally, the combination therapies exerted more potent antiproliferative effects in vitro in EGFR-, ALK-, or ROS1-altered NSCLC cells, implying that VEGFR2 inhibition also has direct anti-tumor effects on cancer cells. Furthermore, VEGFR2 expression was induced following exposure to molecular targeted agents, implying the importance of VEGFR2 signaling in NSCLC patients undergoing molecular targeted therapy. In conclusion, VEGFR2 inhibition enhanced the anti-tumor effects of molecular targeted agents in various oncogene-driven NSCLC models, not only by inhibiting tumor angiogenesis but also by exerting direct antiproliferative effects on cancer cells. Hence, combination therapy with anti-VEGFR2 antibodies and molecular targeted agents could serve as a promising treatment strategy for oncogene-driven NSCLC. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 00092541 559 2021 Experimental variable effects on laser heating of inclusions during Raman spectroscopic analysis 119928 EN Yuuki Hagiwara Graduate School of Science, Hokkaido University Kenta Yoshida Research Institute for Marine Geodynamics, Japan Agency for Marine-Earth Science and Technology (JAMSTEC) Akira Yoneda Institute for Planetary Materials, Okayama University Junji Torimoto Ore Genesis Research Unit, Project Team for Development of New-Generation Research Protocol for Submarine Resources, Japan Agency for Marine-Earth Science and Technology (JAMSTEC) Junji Yamamoto The Hokkaido University Museum Raman spectroscopy for fluid, melt, and mineral inclusions provides direct insight into the physicochemical conditions of the environment surrounding the host mineral at the time of trapping. However, the obtained Raman spectral characteristics such as peak position are modified because of local temperature enhancement of the inclusions by the excitation laser, which might engender systematic errors and incorrect conclusions if the effect is not corrected. Despite the potentially non-negligible effects of laser heating, the laser heating coefficient (B) (°C/mW) of inclusions has remained unsolved. For this study, we found B from experiments and heat transport simulation to evaluate how various parameters such as experimental conditions, mineral properties, and inclusion geometry affect B of inclusions. To assess the parameters influencing laser heating, we measured B of a total of 19 CO2-rich fluid inclusions hosted in olivine, orthopyroxene, clinopyroxene, spinel, and quartz. Our results revealed that the measured B of fluid inclusions in spinel is highest (approx. 6 °C/mW) and that of quartz is lowest (approx. 1 × 10−2 °C/mW), consistent with earlier inferences. Our simulation results show that the absorption coefficient of the host mineral is correlated linearly with B. It is the most influential parameter when the absorption coefficient of the host mineral (αh) is larger than that of an inclusion (αinc). Furthermore, although our results indicate that both the inclusion size and depth have little effect on B if αh > αinc, the thickness and radius of the host mineral slightly influence B. These results suggest that the choice of inclusion size and depth to be analyzed in a given sample do not cause any systematic error in the Raman data because of laser heating, but the host radius and thickness, which can be adjusted to some degree at the time of sample preparation, can cause systematic errors between samples.Our results demonstrate that, even with laser power of 10 mW, which is typical for inclusion analysis, the inclusion temperature rises to tens or hundreds of degrees during the analysis, depending especially on the host mineral geometry and optical properties. Therefore, correction of the heating effects will be necessary to obtain reliable data from Raman spectroscopic analysis of inclusions. This paper presents some correction methods for non-negligible effects of laser heating. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1880-6546 70 1 2020 Effectiveness of impedance parameters for muscle quality evaluation in healthy men 53 EN Hiroki Sato Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Takao Nakamura Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Toshimasa Kusuhara Department of Radiological Technology, Graduate School of Health Sciences, Okayama University Kobara Kenichi Department of Physical Therapist, Faculty of Rehabilitation, Kawasaki University of Medical Welfare Katsushi Kuniyasu Department of Physical Therapist, Faculty of Rehabilitation, Kawasaki University of Medical Welfare Takaki Kawashima Department of Physical Therapist, Kawasaki Junior College of Rehabilitation Kozo Hanayama Department of Rehabilitation Medicine, Kawasaki Medical School, 577, Matsushim We investigated the relationship between impedance parameters and skeletal muscle function in the lower extremities, as well as the effectiveness of impedance parameters in evaluating muscle quality. Lower extremity impedance of 19 healthy men (aged 23–31 years) measured using the direct segmental multi-frequency bioelectrical impedance analysis were arc-optimized using the Cole–Cole model, following which phase angle (PA), Ri/Re, and β were estimated. Skeletal muscle function was assessed by muscle thickness, muscle intensity, and isometric knee extension force (IKEF). IKEF was positively correlated with PA (r = 0.58, p < 0.01) and β (r = 0.34, p < 0.05) was negatively correlated with Ri/Re (r = − 0.43, p < 0.01). Stepwise multiple regression analysis results revealed that PA, β, and Ri/Re were correlated with IKEF independently of muscle thickness. This study suggests that arc-optimized impedance parameters are effective for evaluating muscle quality and prediction of muscle strength. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1471-2415 20 1 2020 Release and extraction of retained subfoveal perfluorocarbon liquid facilitated by subretinal BSS, vibration, and gravity: a case report 427 EN Kosuke Takahashi Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuhei Kimura Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mio Morizane Hosokawa Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Shiode Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichiro Doi Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Matoba Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Kanzaki Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihiro Yonekawa Wills Eye Hospital, Mid Atlantic Retina, Thomas Jefferson University Yuki Morizane Department of Ophthalmology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background</br> Perfluorocarbon liquid (PFCL) is an effective surgical adjuvant in performing vitrectomy for severe vitreoretinal pathologies such as proliferative vitreoretinopathy and giant retinal tears. However, subretinal retention of PFCL can occur postoperatively and retained PFCL causes severe visual disorders, particularly when PFCL was retained under the fovea. Although several procedures have been proposed for subfoveal PFCL removal, such as direct aspiration or submacular injection of balanced salt solution (BSS) to dislodge the subfoveal PFCL, the retinal damage associated with these procedures has been a major problem. Here, we report a case of subfoveal retention of PFCL for which we performed a novel surgical technique that attempts to minimize retinal damage.</br> Case presentation</br> A 69-year-old man presented with subfoveal retained PFCL after surgery for retinal detachment. To remove the retained PFCL, the internal limiting membrane overlying the subretinal injection site is first peeled to allow low-pressure (8 psi) transretinal BSS infusion, using a 41-gauge cannula, to slowly detach the macula. A small drainage retinotomy is created with the diathermy tip at the inferior position of the macular bleb, sized to be slightly wider than that of the PFCL droplet. The head of the bed is then raised, and the surgeon gently vibrates the patient’s head to release the PFCL droplet to allow it to migrate inferiorly towards the drainage retinotomy. The bed is returned to the horizontal position, and the PFCL, now on the retinal surface, can be aspirated. The subfoveal PFCL is removed while minimizing iatrogenic foveal and macular damage. One month after PFCL removal, the foveal structure showed partial recovery on optical coherence tomography, and BCVA improved to 20/40.</br> Conclusion</br> Creating a macular bleb with low infusion pressure and using vibrational forces and gravity to migrate the PFCL towards a retinotomy can be considered as a relatively atraumatic technique to remove subfoveal retained PFCL. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 5 2020 Three-dimensional Evaluation of Abnormal Gait in Patients with Hip Osteoarthritis 391 399 EN Daisuke Homma Division of Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Sciences Izumi Minato Division of Orthopedic Surgery, Niigata Rinko Hospital Norio Imai Division of Comprehensive Geriatrics in Community, Niigata University Graduate School of Medical and Dental Sciences Dai Miyasaka Division of Orthopedic Surgery, Niigata Bandai Hospital Yoshinori Sakaif Division of Orthopedic Surgery, Niigata General Hospital Yoji Horigome Division of Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Sciences Hayato Suzuki Division of Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Sciences Hayato Shimada Division of Orthopedic Surgery, Mito Saiseikai General Hospital Yoichiro Dohmae Division of Orthopedic Surgery, Niigata Bandai Hospital Naoto Endo Division of Orthopedic Surgery, Niigata University Graduate School of Medical and Dental Sciences Original Article 10.18926/AMO/60798 Indexes for objectively evaluating abnormal gait in hip osteoarthritis (OA) patients and determining effective interventions are unclear. We analyzed the abnormal gait of hip OA patients by focusing on movements of the trunk and pelvis to establish an effective evaluation index for each direction of motion. We studied 28 patients with secondary hip OA due to developmental dysplasia of the hip and 16 controls. The trunk and pelvic movements during gait were measured in the medial-lateral (x), vertical (y), and back-and-forth (z) directions by a triaxial angular accelerometer. Gait speed, steps, step length, muscle strength, range of motion, and timed up-and-go (TUG) test performance were measured. We determined the correlations between physical function and the index of abnormal gait in the hip OA patients. Movements other than trunk and pelvic motions in the y-direction indicated abnormal gait in the patients. Significant correlations were found between abnormal gait and range of motions (extension, internal rotation), TUG score, stride length, and steps. The TUG test, stride length and steps were important for evaluating abnormal gait in hip OA patients. Individual interventions for each movement direction are required. No potential conflict of interest relevant to this article was reported.

Pergamon Acta Medica Okayama 0278-6915 138 2020 Effects of maternal bisphenol A diglycidyl ether exposure during gestation and lactation on behavior and brain development of the offspring 111235 EN Ikuko Miyazaki Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryo Kikuoka Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Nami Isooka Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mika Takeshima Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kanau Sonobe Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Rei Arai Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hidemaru Funakoshi Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kyle E. Quin Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Smart Smart Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazumasa Zensho Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masato Asanuma Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Bisphenol A diglycidyl ether (BADGE) is an epoxy resin used for the inner coating of canned food and beverages. BADGE can easily migrate from the containers and become a contaminant. In this study, we examined the effects of BADGE exposure to the dams on the behavioral, structural, and developmental abnormalities in the offspring. Female pregnant mice were fed with a diet containing BADGE (0.15 or 1.5 mg/kg/day) during gestation and lactation periods. In an open field test, the time spent in the corner area significantly increases in male mice of high-dose BADGE group at 5 weeks old. The histological analysis using offspring brain at postnatal day 1 delivered from BADGE (1.5 mg/kg/day)-treated dams demonstrates that positive signals of Forkhead box P2- and COUP-TF interacting protein 2 are restricted in each cortical layer, but not in the control brain. In addition, the maternal BADGE exposure reduces nestin-positive fibers of the radial glia and T-box transcription factor 2-positive intermediate progenitors in the inner subventricular zone. Furthermore, a direct BADGE exposure promotes neurite outgrowth and neuronal connection in the primary cultured cortical neurons. These data suggest that maternal BADGE exposure can accelerate neuronal differentiation in fetuses and induce anxiety-like behavior in juvenile mice. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 74 2 2020 Increased Plasma Levels of Platelet Factor 4 and β-thromboglobulin in Women with Recurrent Pregnancy Loss 115 122 EN Sayoko Kotani Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiko Kamada Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiko Shimizu Okayama Rosai Hospital Ai Sakamoto Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mikiya Nakatsuka Graduate School of Health Sciences, Okayama University Yuji Hiramatsu Okayama City Hospital Hisashi Masuyama Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/58269 Thrombosis in decidual vessels is one of the mechanisms of pregnancy loss. However, few studies have assessed the relation between platelet activation, which is known to cause of thrombosis, and recurrent pregnancy loss (RPL). We investigated platelet activation in women with RPL compared to controls by measuring plasma levels of platelet factor 4 (PF4) and β-thromboglobulin (βTG), and assessed correlations between PF4/βTG and coagulative risk factors associated with RPL. The study group included 135 women who had experienced two or more consecutive pregnancy losses. The control group included 28 age-matched healthy women who had never experienced pregnancy loss. PF4 and βTG plasma levels were significantly higher in the women with RPL than controls (PF4: 14.0 [8.0-20.0] vs. 9.0 [6.0-12.0] ng/ml, p=0.043; βTG: 42.0 [24.3-59.8] vs. 31.5 [26.6-36.4] ng/ml, p=0.002). There was a significant association between βTG and anti-phosphatidylethanolamine antibody immunoglobulin M (aPE IgM) (p=0.048). Among the women with RPL, 18 of those who were positive for PF4 (45%) and 18 of those who were positive for βTG (37%) were negative for all known coagulative risk factors associated with RPL. Measurements of PF4 and βTG may be important because they help identify women who are at risk of RPL. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1347-9032 111 3 2019 YES1 activation induces acquired resistance to neratinib in HER2-amplified breast and lung cancers 849 856 EN Tatsuaki Takeda Department of Clinical Pharmacy, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences Hiromasa Yamamoto Department of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ken Suzawa Department of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuta Tomida Center for Comprehensive Genomic Medicine, Okayama University Hospital Shunsaku Miyauchi Department of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kota Araki Department of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Nakata Department of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Miura Department of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kei Namba Department of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Junichi Soh Department of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tadahiko Shien Department of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Kitamura Department of Clinical Pharmacy, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences Toshiaki Sendo Department of Clinical Pharmacy, Okayama University Graduate School of Medicine,Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Molecular-targeted therapies directed against human epidermal growth factor receptor 2 (HER2) are evolving for various cancers. Neratinib is an irreversible pan-HER tyrosine kinase inhibitor and has been approved by the FDA as an effective drug for HER2-positive breast cancer. However, acquired resistance of various cancers to molecular-targeted drugs is an issue of clinical concern, and emergence of resistance to neratinib is also considered inevitable. In this study, we established various types of neratinib-resistant cell lines from HER2-amplified breast and lung cancer cell lines using several drug exposure conditions. We analyzed the mechanisms of emergence of the resistance in these cell lines and explored effective strategies to overcome the resistance. Our results revealed that amplification of YES1, which is a member of the SRC family, was amplified in two neratinib-resistant breast cancer cell lines and one lung cancer cell line. Knockdown of YES1 by siRNA and pharmacological inhibition of YES1 by dasatinib restored the sensitivity of the YES1-amplified cell lines to neratinib in vitro. Combined treatment with dasatinib and neratinib inhibited tumor growth in vivo. This combination also induced downregulation of signaling molecules such as HER2, AKT and MAPK. Our current results indicate that YES1 plays an important role in the emergence of resistance to HER2-targeted drugs, and that dasatinib enables such acquired resistance to neratinib to be overcome. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-4701 9 7 2019 Effect of Lubrication and Forging Load on Surface Roughness, Residual Stress, and Deformation of Cold Forging Tools 783 EN Nuwan Karunathilaka Graduate School of Natural Science and Technology, Okayama University Naoya Tada Graduate School of Natural Science and Technology, Okayama University Takeshi Uemori Graduate School of Natural Science and Technology, Okayama University Ryota Hanamitsu Graduate School of Natural Science and Technology, Okayama University Masahiro Fujii Graduate School of Natural Science and Technology, Okayama University Yuya Omiya Graduate School of Natural Science and Technology, Okayama University Masahiro Kawano Zeno Tech Co., Ltd Cold forging is a metal forming that which uses localized compressive force at room temperature. During the cold forging process, the tool is subjected to extremely high loads and abrasive wear. Lubrication plays an important role in cold forging to improve product quality and tool life by preventing direct metallic contact. Surface roughness and residual stress also greatly affects the service life of a tool. In this study, variations in surface roughness, residual stress, and specimen deformation with the number of cold forging cycles were investigated under different forging conditions. Specimens that were made of heat-treated SKH51 (59-61 HRC), a high-speed tool steel with a polished working surface, were used. The specimens were subjected to an upsetting process. Compressive residual stress, surface roughness, and specimen deformation showed a positive relationship with the number of forging cycles up to a certain limit and became almost constant in most of the forging conditions. A larger change in residual stress and surface roughness was observed at the center of the specimens in all the forging conditions. The effect of the magnitude of the forging load on the above discussed parameters is large when compared to the effect of the lubrication conditions. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 20 5 2019 Targeting Ovarian Cancer Cells Overexpressing CD44 with Immunoliposomes Encapsulating Glycosylated Paclitaxel 1042 EN Apriliana Cahya Khayrani Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Hafizah Mahmud Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Maram H. Zahra Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Aung Ko Ko Oo Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Miharu Oze Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Juan Du Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Md Jahangir Alam Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Said M. Afify Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Hagar A. Abu Quora Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Tsukasa Shigehiro Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Anna Sanchez Calle Division of Molecular and Cellular Medicine, National Cancer Center Research Institute Nobuhiro Okada Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Akimasa Seno Laboratory of Nano-Biotechnology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Koki Fujita Ensuiko Sugar Refining Co., Ltd. Hiroki Hamada Faculty of Science, Okayama University of Science Yuhki Seno Graduate School of Pharmaceutical Science, Tokushima University Tadakatsu Mandai Faculty of Life Science, Kurashiki University of Science and the Arts Masaharu Seno Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University Paclitaxel (PTX) is one of the front-line drugs approved for the treatment of ovarian cancer. However, the application of PTX is limited due to the significant hydrophobicity and poor pharmacokinetics. We previously reported target-directed liposomes carrying tumor-selective conjugated antibody and encapsulated glycosylated PTX (gPTX-L) which successfully overcome the PTX limitation. The tubulin stabilizing activity of gPTX was equivalent to that of PTX while the cytotoxic activity of gPTX was reduced. In human ovarian cancer cell lines, SK-OV-3 and OVK18, the concentration at which cell growth was inhibited by 50% (IC50) for gPTX range from 15⁻20 nM, which was sensitive enough to address gPTX-L with tumor-selective antibody coupling for ovarian cancer therapy. The cell membrane receptor CD44 is associated with cancer progression and has been recognized as a cancer stem cell marker including ovarian cancer, becoming a suitable candidate to be targeted by gPTX-L therapy. In this study, gPTX-loading liposomes conjugated with anti-CD44 antibody (gPTX-IL) were assessed for the efficacy of targeting CD44-positive ovarian cancer cells. We successfully encapsulated gPTX into liposomes with the loading efficiency (LE) more than 80% in both of gPTX-L and gPTX-IL with a diameter of approximately 100 nm with efficacy of enhanced cytotoxicity in vitro and of convenient treatment in vivo. As the result, gPTX-IL efficiently suppressed tumor growth in vivo. Therefore gPTX-IL could be a promising formulation for effective ovarian cancer therapies. No potential conflict of interest relevant to this article was reported.

Elsevier B.V. Acta Medica Okayama 24056502 16 2019 Effect of intravenous immunoglobulin therapy on anti-NT5C1A antibody-positive inclusion body myositis after successful treatment of hepatitis C: A case report 100204 EN Motonori Takamiya Department of Neurology, Kagawa Prefectural Central Hospital Yoshiaki Takahashi Department of Neurology, Kagawa Prefectural Central Hospital Mizuki Morimoto Department of Neurology, Kagawa Prefectural Central Hospital Nobutoshi Morimoto Department of Neurology, Kagawa Prefectural Central Hospital Satoshi Yamashita Department of Neurology, Graduate School of Medical Sciences, Kumamoto University Koji Abe Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Inclusion body myositis (IBM) is the commonest idiopathic inflammatory myopathy of older persons. Pathophysiological mechanism of IBM remains unknown; however, an association of IBM with chronic hepatitis C virus (HCV) infection and serum autoantibodies against skeletal muscle protein 5′-nucleotidase 1A (NT5C1A) has recently been reported. No effective treatment for IBM has yet been developed. We here present a 70-year-old man who was anti-NT5C1A antibody-positive in association with IBM and chronic hepatitis C. The initial treatment of ombitasvir/paritaprevir/ritonavir for his chronic hepatitis C was successful; however, his symptoms of IBM did not improve. On the contrary, his quadriplegic paralysis became more severe and he developed dysphagia. Next, steroid pulse therapy was initiated for IBM and, although his hyper-creatine phosphokinase-emia improved, his symptoms did not; indeed, they worsened. Subsequent intravenous immunoglobulin therapy (IVIg) resulted in obvious improvement in his dysphagia. Thereafter IVIg therapy was repeated at approximately 2-monthly intervals. His dysphagia remained improved for more than 1 year; however, his quadriplegia continued to progress slowly. Although IBM can reportedly be associated with hepatitis C, we inferred that there was no direct relationship between these conditions in our patient because his IBM did not improve after treatment of his hepatitis C. Although his IBM-associated quadriplegia did not improve, IVIg therapy did result in improvement in his dysphagia. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 15560864 14 11 2019 Rapid Acquisition of Alectinib Resistance in ALK-Positive Lung Cancer With High Tumor Mutation Burden 2009 2018 EN Go Makimoto Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kadoaki Ohashi Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuta Tomida Okayama University Hospital Biobank, Okayama University Hospital Kazuya Nishii Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Matsubara Okayama University Hospital Biobank, Okayama University Hospital Hiroe Kayatani Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hisao Higo Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kiichiro Ninomiya Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akiko Sato Department of Respiratory Medicine, Okayama University Hospital Hiromi Watanabe Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirohisa Kano Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Ninomiya Department of Respiratory Medicine, Okayama University Hospital Toshio Kubo Center for Clinical Oncology, Okayama University Hospital Kammei Rai Department of Respiratory Medicine, Okayama University Hospital Eiki Ichihara Department of Respiratory Medicine, Okayama University Hospital Katsuyuki Hotta Center of Innovative Clinical Medicine, Okayama University Hospital Masahiro Tabata Center for Clinical Oncology, Okayama University Hospital Shinichi Toyooka Okayama University Hospital Biobank, Okayama University Hospital Minoru Takata Laboratory of DNA Damage Signaling, Department of Late Effects Studies, Graduate School of Biostudies, Radiation Biology Center, Kyoto University Yoshinobu Maeda Department of Hematology, Oncology and Respiratory Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Katsuyuki Kiura Department of Respiratory Medicine, Okayama University Hospital Introduction<br/> The highly selective ALK receptor tyrosine kinase (ALK) inhibitor alectinib is standard therapy for ALK-positive lung cancers; however, some tumors quickly develop resistance. Here, we investigated the mechanism associated with rapid acquisition of resistance using clinical samples. <br/> Methods<br/> Autopsied samples were obtained from lung, liver, and renal tumors from a 51-year-old male patient with advanced ALK-positive lung cancer who had acquired resistance to alectinib in only 3 months. We established an alectinib-resistant cell line (ABC-14) from pleural effusion and an alectinib/crizotinib-resistant cell line (ABC-17) and patient-derived xenograft (PDX) model from liver tumors. Additionally, we performed next-generation sequencing, direct DNA sequencing, and quantitative real-time reverse transcription polymerase chain reaction. <br/>Results<br/> ABC-14 cells harbored no ALK mutations and were sensitive to crizotinib while also exhibiting MNNG HOS transforming gene (MET) gene amplification and amphiregulin overexpression. Additionally, combined treatment with crizotinib/erlotinib inhibited cell growth. ABC-17 and PDX tumors harbored ALK G1202R, and PDX tumors metastasized to multiple organs in vivo, whereas the third-generation ALK-inhibitor, lorlatinib, diminished tumor growth in vitro and in vivo. Next-generation sequencing indicated high tumor mutation burden and heterogeneous tumor evolution. The autopsied lung tumors harbored ALK G1202R (c. 3604 G>A) and the right renal metastasis harbored ALK G1202R (c. 3604 G>C); the mutation thus comprised different codon changes. <br/>Conclusions<br/> High tumor mutation burden and heterogeneous tumor evolution might be responsible for rapid acquisition of alectinib resistance. Timely lorlatinib administration or combined therapy with an ALK inhibitor and other receptor tyrosine-kinase inhibitors might constitute a potent strategy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 4 2019 Dynamic Reorganization of Microtubule and Glioma Invasion 285 297 EN Yoshihiro Otani Department of Neurosurgery, The University of Texas Health Science Center at Houston Tomotsugu Ichikawa Department of Neurosurgery, Kagawa Prefectural Central Hospital Kazuhiko Kurozumi Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Isao Date Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Review 10.18926/AMO/56930 Gliomas are characterized as highly diffuse infiltrating tumors, and currently available treatments such as surgery, radiation and chemotherapy are unfeasible or show limited efficacy against these tumors. Recent genetic and epigenetic analyses of glioma have revealed increasing evidence of the role of driver genetic alterations in glioma development and led to the identification of prognostic factors. Despite these findings, the survival rates of glioma patients remain low, and alternative treatments and novel targets are needed. Recent studies identified neural stem cells as the possible origin of gliomas, and some evidence has revealed shared functions and mechanisms between glioma cells and neurons, also supporting their similarity. The cytoskeleton plays important roles in the migration of normal cells as well as cancer cells. Recent reports have described a role for microtubules, a component of the cytoskeleton, in glioma invasion. Notably, several factors that regulate microtubule functions, such as microtubule-associated proteins, plus-end tracking proteins, or motor proteins, are upregulated in glioma tissues compared with normal tissue, and upregulation of these factors is associated with high invasiveness of glioma cells. In this review, we describe the mechanism of microtubules in glioma invasion and discuss the possibility of microtubule-targeted therapy to inhibit glioma invasion. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 73 2 2019 Unintentional Injury Deaths among Children: A Descriptive Study Using Medico-legal Documents in Okayama Prefecture, Japan (2001−2015) 117 125 EN Yukie Yamasaki Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nanako Tamiya Department of Health Services Research, Faculty of Medicine, University of Tsukuba, Hideki Yamamoto Graduate School of Public Health, Teikyo University Satoru Miyaishi Department of Legal Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/56647 According to the World Health Organization’s World Report, approx. 950,000 children and young people < 18 years old die from an injury each year, and unintentional injury deaths account for a large portion of these cases. Here we used medico-legal documents to epidemiologically analyze the cases of unintentional injury deaths among children < 5 years old in Okayama Prefecture, Japan from 2001 to 2015. Age, sex, manner/cause of death, and various circumstances of the incident were investigated. There were 73 unintentional injury deaths during the study period. Drowning (n=29), suffocation (n=24), and transport accidents (n=13) were the major categories of unintentional injury deaths. Twenty-two cases (30.1%) were autopsied. Differences in the characteristics of the unintentional injury deaths by age were observed. Information which cannot be obtained from Vital Statistics was available from medico-legal documents, and detailed characteristics of unintentional injury deaths among children < 5 years old were elucidated. Investigating medico-legal information is one of the meaningful measures for the prevention of unintentional injury deaths among children in Japan. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2210-7703 37 6 2015 Exploring autistic-like traits relating to empathic attitude and psychological distress in hospital pharmacists 1258 1266 EN Yuji Higuchi Department of NeuropsychiatryOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Uchitomi Innovation Center for Supportive, Palliative and Psychosocial CareNational Cancer Center Maiko Fujimori Center for Suicide Prevention, National Institute of Mental HealthNational Center for Neurology and Psychiatry Toshihiro Koyama Department of Clinical PharmacyOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitomi Kataoka Department of Primary Care and Medical EducationOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Kitamura Department of Clinical PharmacyOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Sendo Department of Clinical PharmacyOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masatoshi Inagaki Department of NeuropsychiatryOkayama University Hospital BACKGROUND: Pharmacists are expected to play a key role in modern cancer care. Research suggests that an empathic approach and attitude in medical staff improves the quality of patient care. An empathic attitude and psychological distress are thought to be associated with autistic-like traits, but little is known about such traits. OBJECTIVE: In this study, we aimed to clarify the associations among autistic-like traits, empathic attitude in a medical context, and psychological health in hospital pharmacists. SETTING: Eligibility criteria for inclusion were certified pharmacists working at hospitals for patient care who returned their questionnaires. METHOD: Eight hundred and twenty-three hospital pharmacists completed a number of self-administered questionnaires anonymously by mail. MAIN OUTCOME MEASURES: Scores were obtained on the Autism-Spectrum Quotient, the Jefferson Scale of Empathy, the General Health Questionnaire-12, and subscales of the Interpersonal Reactivity Index (Perspective Taking, IRI-Empathic Concern, IRIPersonal Distress). We performed correlation and mediation analyses to confirm that the empathy and general health questionnaires were associated with autism-spectrum quotient scores, and with each IRI subscale. RESULTS: Complete responses were obtained from 379 pharmacists comprising 151 males (39.8 %) with a mean age of 37.7 ± 10.8 years (missing data, n = 13) and a median of 11 years after qualification as a pharmacist. Autism-Spectrum Quotient scores were inversely correlated with empathy (r = -0.22, p < 0.001) and positively correlated with general health scores (r = 0.40, p < 0.001). In the models with mediation, the inverse correlation between autism-spectrum quotient and empathy scores was mediated indirectly by IRI-Perspective Taking and IRI-Empathic Concern, and the positive correlation between autism-spectrum quotient and general health was mediated indirectly by IRI-Personal Distress. There were also direct effects, with significant effects of autism-spectrum quotient on empathy and general health scores. CONCLUSION: Our findings suggest that autistic-like traits affect both empathic attitude in a medical context and the psychological health of pharmacists. We recommend that to improve empathy in those with high levels of autistic-like traits, we may need to develop specialized interventions, such as improving communication skills training. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 127 3 2015 術前内照射および化学療法が著効し,根治切除し得た巨大異所性褐色細胞腫の1例 213 218 EN Kazuya Yasui Yuzo Umeda Kenjiro Kumano Masahiro Tabata Fumio Otsuka Takahito Yagi Toshiyoshi Fujiwara A 46-year-old man was found to be positive for occult blood at a medical checkup and was revealed to have a 14-cm tumor on the right side of abdominal aorta by a subsequent abdominal CT scan. The endocrinology laboratory data showed elevations in the levels of serum noradrenaline, and ectopic pheochromocytoma was suspected. The tumor was compressing the inferior vena cava and portal vein, the superior mesenteric artery and the pancreas. Since it would be difficult to cure by operation, neoadjuvant therapy was started using radioisotope therapy by I-131 metaiodobenzylguanidine (131I-MIBG) and chemotherapy (CVD therapy ; cyclophosphamide, vincristine, dacarbazine). He was treated with three courses of radioisotope therapy and 16 courses of chemotherapy, which significantly reduced the tumor size. This made radical resection possible ; we were able to avoid the merger excision of great vessels and other organs. On pathological and immunopathological findings, the tumor was diagnosed as ectopic　pheochromocytoma. Regarding the safety and curability of the treatment, neoadjuvant therapy may be useful in treating very large tumors that show invasion of other organs. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 69 1 2015 Trend of Human Papillomavirus Genotypes in Cervical Neoplasia Observed in a Newly Developing Township in Yangon, Myanmar 51 58 EN Mu Mu Shwe Kyi Kyi Nyunt Shigeru Okada Teruo Harano Hlaing Myat Thu Hla Myat Mo Mo Mo Mo Win Khin Khin Oo KhinThet Wai Khin Saw Aye Myo Khin Original Article 10.18926/AMO/53122 Persistent infection with oncogenic types of human papillomavirus (HPV) is the most important risk factor associated with cervical cancer. This study detected the oncogenic HPV genotypes in cervical neoplasia in relation to clinicopathological findings using a cross-sectional descriptive method in 2011 and 2012. Cervical swabs and colposcopy-directed cervical biopsy tissues were collected from 108 women (median age 45 years;range 20-78) showing cervical cytological changes at Sanpya General Hospital, Yangon, Myanmar. HPV DNA testing and genotyping were performed by polymerase chain reaction and restriction fragment length polymorphism. HPV was identified in women with cervical intraepithelial neoplasia (CIN) 1 (44.4%), CIN2 (63.2%), CIN3 (70.6%), and squamous cell carcinoma (SCC) (74.1%). The association between cervical neoplasia and HPV positivity was highly significant (p＝0.008). Most patients infected with HPV were between 40-49 years of age, and the youngest were in the 20- to 29-year-old age group. The most common genotype was HPV 16 (65.6%) with the following distribution:70% in CIN1, 41.7% in CIN2, 91.7% in CIN3, and 60% in SCC. HPV-31 was the second-most frequent (21.9%):30% in CIN1, 33.3% in CIN2, 8.3% in CIN3, and 15% in SCC. The third-most frequent-genotype was HPV-18 (7.8%):8.3% in CIN1, and 20% in SCC. Another genotype was HPV-58 (4.7%):16.7% in CIN1 and 5% in SCC. The majority of CIN/SCC cases were associated with HPV genotypes 16, 31, 18, and 58. If oncogenic HPV genotypes are positive, the possibility of cervical neoplasia can be predicted. Knowledge of the HPV genotypes distribution can predict the effectiveness of the currently used HPV vaccine. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2041-4889 5 2014 Nuclear factor-kappaB sensitizes to benzyl isothiocyanate-induced antiproliferation in p53-deficient colorectal cancer cells EN N Abe D-X Hou S Munemasa Y Murata Y Nakamura Benzyl isothiocyanate (BITC), a dietary isothiocyanate derived from cruciferous vegetables, inhibits the proliferation of colorectal cancer cells, most of which overexpress β-catenin as a result of mutations in the genes for adenomatous polyposis coli or mutations in β-catenin itself. Because nuclear factor-κB (NF-κB) is a plausible target of BITC signaling in inflammatory cell models, we hypothesized that it is also involved in BITC-inhibited proliferation of colorectal cancer cells. siRNA-mediated knockdown of the NF-κB p65 subunit significantly decreased the BITC sensitivity of human colorectal cancer HT-29 cells with mutated p53 tumor suppressor protein. Treating HT-29 cells with BITC induced the phosphorylation of IκB kinase, IκB-α and p65, the degradation of IκB-α, the translocation of p65 to the nucleus and the upregulation of NF-κB transcriptional activity. BITC also decreased β-catenin binding to a positive cis element of the cyclin D1 promoter and thus inhibited β-catenin-dependent cyclin D1 transcription, possibly through a direct interaction between p65 and β-catenin. siRNA-mediated knockdown of p65 confirmed that p65 negatively affects cyclin D1 expression. On the other hand, when human colorectal cancer HCT-116 cells with wild-type p53 were treated with BITC, translocation of p65 to the nucleus was inhibited rather than enhanced. p53 knockout increased the BITC sensitivity of HCT-116 cells in a p65-dependent manner, suggesting that p53 negatively regulates p65-dependent effects. Together, these results identify BITC as a novel type of antiproliferative agent that regulates the NF-κB pathway in p53-deficient colorectal cancer cells. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 124 3 2012 高分化型ヒト肝癌由来細胞株“HuH-7” 231 238 EN Hidekazu Nakabayashi Kazuhisa Taketa 高分化型ヒト肝癌由来細胞株“HuH-7”は，1982年にCancer Researchにその樹立を報告した．HuH-7は，当時の岡山大学医学部附属癌源研究施設病理部門（故佐藤二郎教授）の下で樹立し，これまで多くの研究分野で利用され，世界的に有名な肝癌細胞株となっている．本稿では，有用性の高い分化機能を有するヒト肝癌細胞株HuH-7について，肝細胞癌の腫瘍マーカーであるα-fetoprotein（AFP）を中心に，この細胞株を用いた研究分野に関する詳細を紹介する． No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 0169-1864 25 9-10 2011 Miniature Pneumatic Curling Rubber Actuator Generating Bidirectional Motion with One Air-Supply Tube 1311 1330 EN Shuichi Wakimoto Koichi Suzumori Keiko Ogura Soft actuators driven by pneumatic pressure are promising actuators for mechanical systems in medical, biological, agriculture, welfare fields and so on, because they can ensure high safety for fragile objects from their low mechanical impedance. In this study, a new rubber pneumatic actuator made from silicone rubber was developed. Composed of one chamber and one air-supply tube, it can generate curling motion in two directions by using positive and negative pneumatic pressure. The rubber actuator, for generating bidirectional motion, was designed to achieve an efficient shape by nonlinear finite element method analysis, and was fabricated by a molding and rubber bonding process using excimer light. The fabricated actuator was able to generate curling motion in two directions successfully. The displacement and force characteristics of the actuator were measured by using a motion capture system and a load cell. As an example application of the actuator, a robotic soft hand with three actuators was constructed and its effectiveness was confirmed by experiments. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 11-2 1959 黄疸患者の皮膚の酸化還元電位とbilirubinの沈着に関する研究 第1編 黄疸患者の皮膚の酸化還元電位に関する研究 7783 7802 EN Tetsusaburo Ishimitsu With the purpose to clarify the condition of oxidation-reduction potential in the skin of jaundiced patients, the author made the preliminary experiment by the injection of 2. 3. 5. triphenyl tetrazolium chloride, neo tetrazolium chloride and blue tetrazolium into dogs and rabbits, employing the Arakawa's method, and it was recognized the T. T. C. test by Arakawa was the best method to apply to human body. Therefore, the test was attempted on 20 cases of healthy human, 110 cases of various liver and bile ducts diseases (75 cases of them showed hyperbilirubinemia over 1 mg/dl) and 21 cases of other diseases, and the above results was compared with various clinical symptoms and clinical courses. And the results were as follows. 1. Using the above agents as a oxidation-reduction. dicator of skin in living body, the sensitivity was in order of N. T C., T. T. C. and B. T., but the side effect was the most scanty in T. T. C., Therefore, the T. T. C. test by Arakawa was the best for the application to human body, and N. T. C. had the utility value on the animal experiment since the stability and sensitivity to light, but B. T. could not use. 2. The difference of oxidation-reduction potential among healty human, dog and rabbit was clearly observed, and this test was the most in rabbit, and then in dog, and the most low in human. 3. The T. T. C. test was almost negative in healthy human, but in was positive in all cases of mechanical jaundice, and it showed positive by the stadium or symptom in acute hepatitis and livercirrhosis, and it was seen at the early period of acute stadium in the former and it was seen in the cases of the latter with continuous jaundice over 60 days. In and it was negative or slight positive in chronic hepatitis. It was negative in hemolytic jaundice and others. 4. Comparing T. T. C. test with various clinical symptoms and various clinical tests, it had relation to serum total bilirubin especially direct bilirubin, alkaline phosphatase and skin itching, and it had considerable relation to serum colloidal reaction in acute hepatitis and BSP-test. 5. Therefore, it was thought that there were close correlation between the oxidationreduction potential of skin and the mechanism in which Verdinikterus was occured from the change of disposed bilirubin in skin to biliverdin. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 11-1 1959 Bilirubinのdiazo反応に及ぼす界面活性剤の影響 第2篇 Bilirubin dimethylesterへの影響 7179 7184 EN Toshio Inoué Selecting solvent that dissolves interface activating reagents and bilirubin dimethylester relatively well and dissolving each of them the author prepared an interface active bilirubin-dimethylester aqueous solution. Then evaqorating this solution at 80°C under a lolw pressure, the auther studied the chemical proqerties of the vaqor dissolved in water and compare with the proqerties of bilirubin. The following are the results of this comparative study. 1. Each interface activating reagent possesses the specific capacity to dissolve bilirubin-dimethlyester in water, and there is a direct-proportion relationship between the quantity of bilirubin dimethylester dissolved in water and quantiy of activating reagent required for the dissolution. The bilirubindimethylester dissolving capacity of each reagent is 1.5 to 4.0 times the bilirubin dissolving capacity. 2. The absorption curve of the bilirubin-dimethylester aquoeus solution has its maximum at 420 mμ, and with the increase in the quantity of the activation reagent added, the maximum absorption curve moves 5-10 mμ towards the long side of short wave. However, in the case of non-ionic activating reagent hardly any such change occurs. 3. The bilirubin-dimethylester aqueous solution is always positive to the direct diazo reaction, and its sensitivity to diazo is not affected by the quantity of activating reagent but is fixed. 4. About 50-75 per cent diazo reaction of the bilirubidimethylester aqueous solution is completed within 5 minutes, but it requires about 40 minutes for its completion. 5. Spectroscopically there is no great difference between bilirubin-dimethylester azo and bilirubin azo, but the optical desnity at 490 mμ on the long side of short wave is higher in the former. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 11-1 1959 Bilirubinのdiazo反応に及ぼす界面活性剤の影響 第1篇 Bilirubinへの影響 7171 7177 EN Toshio Inoué By selecting the solvent that dissolves interface activating reagents and bilirubin relatively well and after dissolving each the author prepared an interface activ bilirubin aqueous solution. This solution was evaporated at 80°C under a low pressure and the solubility in water and the chemical properties of the vapor were studied; and the following ressults were obtained. 1. Each interface activation reagent possesses its own specific capacity to dissolve bilirubin in water, and there is almost a direct-proportion relation between the quantity of bilirubin dissolved in water and the quantity of activating reagent required for such a dissolution. 2. The absorption curve of the bilirubin aqueous solution shows its maximum at 450 mμ, and with the increase in the quantity of the loaded activating reagent the absorption maximum moves 5-10 mμ towards the long side of the short wave; but in the case using non-ionic reagent the absorption maximum remains almost unchanged. 3. The bilirubin aqueous solution is positive to the direct diazo reaction, and its sensitivity to the diazo reaction is proportional to the quantity of the activating reagent added, making the maximum sensitvity to the diazo reaction stable beyond a given quantity. Therefore, the dissolution of bilirubin in water by the aid of the interface activating reagent and the positivity to the diazo reaction are two different phenomena. Thus it is impossible to say that the dissolution of bilirubin in water make it positive to the direct diazo reaction. 4. The bilirubin aqueous solution by the aid of interface activating reagent required 40 to 60 minutes for the completion of diazo reaction and the production of azo dye is about directly proportional to the time required for its production. 5. The absorption maximum of azo dye produced the diazo reaction always at 530 mμ even when pH of the solvent is changed, and the optical density increases proportionately to the strength of acidity. At the same pH the optical density at 530 mμ of azo dye produced by ionic activating reagent is higher than that of the azo dye produced by non-ionic activating reagent; whereas the optical density of 470 mμ on the long side of short wave, on the contrary, of the azo dye produced by non-ionic activating reagent is higher. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 71 10-1 1959 Dimethoxyisoquinoline誘導体についての二，三薬理学的検索 6223 6230 EN Akio Kuroda Kei Jinzenji Takashi Yamamoto Kazuji Kondo Junzo Shoda Twelve members of a new series of 1-trialkylmethyl-1-6, 7-dimethoxy-3, 4-dihydroisoquinoline (D type) and eleven analogs of 1-trialkylmethyl-6, 7-dimethoxy isoquinoline (I type) were investigated for their pharmacological properties, with special reference to the toxicity and spasmolytic activity, comparing with papaverine. Along these isoquinoline, 1-methylisoquinoline, 6, 7-dimethoxyisoquinoline and their respective 3, 4-hydrogenated derivatives, were also examined for the elucidation of structure-activity relationship. All the compounds of D type produced a marked inhibitory action on the isolated rabbit intestine. The most potent members were n-tripropyl, ethyl-n-propyl-n-butyl and methyl-ethyl-n-butyl derivatives. Their spasmolytic actions on both barium and histamine contraction of the intestine exceeded those of papaverine, though the effect on acetylcholine spasm was slightly inferior. They were less toxic in mice than in the latter. The intestine inhibitory activity and toxicity of I Type compounds were both smaller than those of D type analogs. The differences between the two types seemed to be related to the solubility. Other smaller components of the papaverine structure, namely, the primitive isoquinoline derivatives were more toxic, but much less spasmolytic than papaverine. In mice toxic doses of all the compounds caused tremors, excitability and convulsions followed by a generalized central depression. Respiratory paralysis may be direct cause of death. Toxic symptoms were generally similar to those in frogs. The stimulant properties were increased by the saturation of the 3, 4-position on the isoquinoline nucleus. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 74 2 2006 Thermal fluctuations of vortex clusters in quasi-two-dimensional bose-einstein condensates EN W V Pogosov K Machida <p>We study the thermal fluctuations of vortex positions in small vortex clusters in a harmonically trapped rotating Bose-Einstein condensate. It is shown that the order-disorder transition of two-shell clusters occurs via the decoupling of shells with respect to each other. The corresponding "melting" temperature depends strongly on the commensurability between numbers of vortices in shells. We show that melting can be achieved at experimentally attainable parameters and very low temperatures. Also studied is the effect of thermal fluctuations on vortices in an anisotropic trap with small quadrupole deformation. We show that thermal fluctuations lead to the decoupling of a vortex cluster from the pinning potential produced by this deformation. The decoupling temperatures are estimated and strong commensurability effects are revealed.</p> No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 123 11 2005 Infrared spectra of seeded hydrogen clusters: (para-H2)N-N2O and (ortho-H2)N-N2O, N=2-13 EN Jian Tang Robert A McKellar <p>High-resolution infrared spectra of clusters containing para-H2 and/or ortho-H2 and a single nitrous oxide molecule are studied in the 2225-cm–1 region of the 1 fundamental band of N2O. The clusters are formed in pulsed supersonic jet expansions from a cooled nozzle and probed using a tunable infrared diode laser spectrometer. The simple symmetric rotor-type spectra generally show no resolved K structure, with prominent Q-branch features for ortho-H2 but not para-H2 clusters. The observed vibrational shifts and rotational constants are reported. There is no obvious indication of superfluid effects for para-H2 clusters up to N=13. Sharp transitions due to even larger clusters are observed, but no definite assignments are possible. Mixed (para-H2)N–(ortho-H2)M–N2O cluster line positions can be well predicted by linear interpolation between the corresponding transitions of the pure clusters.</p> No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 401 2008 Formation of low-resistivity region in p-Si substrate of SiGe/Si episystem by remote-hydrogen plasma treatment 218 221 EN Yoshifumi Yamashita Yoshifumi Sakamoto Yoichi Kamiura Takeshi Ishiyama <p>We have studied effects of hydrogen treatment on the resistivity profile of the SiGe/Si episystem by spreading resistance (SR) method. In this paper, we present experimental findings that hydrogen treatment reduces the resistivity at a specific part in the Si substrate region. This position was confirmed to be under the interface between SiGe and Si that emerged on the bevel surface during hydrogen treatment. We investigated the depth of resistivity-reduced regions which was formed by various hydrogenating conditions and found that the region was extended to the same depth as the penetration depth of hydrogen. We concluded that the low-resistivity region was formed under the influence of hydrogen introduced from bevel surface. We attributed this resistivity reduction to formation of some defects which originally existed at the interface and diffused into Si substrate with hydrogen.</p> No potential conflict of interest relevant to this article was reported.

Blackwell Publishing Acta Medica Okayama 1462-5814 8 6 2006 Identification of glycosylation genes and glycosylated amino acids of flagellin in Pseudomonas syringae pv. tabaci 923 938 EN Fumiko Taguchi Kasumi Takeuchi Etsuko Katoh Katsuyoshi Murata Tomoko Suzuki Mizuri Marutani Takayuki Kawasaki Minako Eguchi Shizue Katoh Hanae kaku Chihiro Yasuda Yoshishige Inagaki Kazuhiro Toyoda Tomonori Shiraishi Yuki Ichinose A glycosylation island is a genetic region required for glycosylation. The glycosylation island of flagellin in Pseudomonas syringae pv. tabaci 6605 consists of three orfs: orf1, orf2 and orf3. Orf1 and orf2 encode putative glycosyltransferases, and their deletion mutants, Delta orf1 and Delta orf2, exhibit deficient flagellin glycosylation or produce partially glycosylated flagellin respectively. Digestion of glycosylated flagellin from wild-type bacteria and non-glycosylated flagellin from Delta orf1 mutant using aspartic N-peptidase and subsequent HPLC analysis revealed candidate glycosylated amino acids. By generation of site-directed Ser/Ala-substituted mutants, all glycosylated amino acid residues were identified at positions 143, 164, 176, 183, 193 and 201. Matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry (MS) analysis revealed that each glycan was about 540 Da. While all glycosylation-defective mutants retained swimming ability, swarming ability was reduced in the Delta orf1, Delta orf2 and Ser/Ala-substituted mutants. All glycosylation mutants were also found to be impaired in the ability to adhere to a polystyrene surface and in the ability to cause disease in tobacco. Based on the predicted tertiary structure of flagellin, S176 and S183 are expected to be located on most external surface of the flagellum. Thus the effect of Ala-substitution of these serines is stronger than that of other serines. These results suggest that glycosylation of flagellin in P. syringae pv. tabaci 6605 is required for bacterial virulence. It is also possible that glycosylation of flagellin may mask elicitor function of flagellin molecule. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 72 3 2005 Structure of spherical Yukawa clusters: A model for dust particles in dusty plasmas in an isotropic environment EN Hiroo Totsuji Takafumi Ogawa Chieko Totsuji Kenji Tsuruta <p>The structure of spherical clusters composed of Yukawa particles is analyzed by molecular dynamics simulations and theoretical approaches as a model for dust particles in dusty plasmas in the isotropic environment. The latter condition is expected to be realized under microgravity or by active cancellation of the effect of gravity on the ground. It is found that, at low temperatures, Yukawa particles form spherical shells and, when scaled by the mean distance, the structure is almost independent of the strength of screening including the case of the Coulomb interaction. The positions and populations of shells and the conditions for the change of the number of shells are expressed by simple interpolation formulas. Shells have an approximately equal spacing close to that of triangular lattice planes in the bulk close-packed structures. It is shown that, when the cohesive energy in each shell is properly taken into account, the shell model reproduces the structure of spherical Yukawa clusters to a good accuracy.</p> No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 70 5 1958 子宮癌患者の尿中活性Estrogenに就いて 1725 1736 EN Kumehiko Mori For a quite long time a considerable attention has been focused on the relationship between the etiology of cancer and estrogen, and experimental and clinical studies have been conducted from various angles. However, studies on this problem by a direct quantitative analysis of estrogen are still meager. The methods of quantitative analysis of estrogen, on the other hand, namely, both the biological and the chemical determinations, have recently been so improved that it is now possible to conduct microdetection of estrogen. Moreover, by chemical determination estrogne can now be estimated so that the actual estrogen metabolism in vivo is being clarified. Therefore, an attempt has been made to explore the relationship between cancer and estrogen. First women over three years past menopause were selected so as to avoid the effect of variations in menstrual period as well as the effect of fluctuations in estrogen at menopause. Active estrogen in urine was then determined in order to estimate indirectly the active estrogen in vivo. These procedures were undertaken for both the non-cancer and the cancer cases for the comparison: and at the same time the active estrogen in cases with cervical cancer were studied in detail by dividing the duration of cancer progress into various stages. The purpose of this paper is to present the findings obtained from the foregoing study. 1) As for the sensitivity of the biological microdetection method devised by us and applied in experimental animals that proved to be over 60 per cent positive, it has been possible to detect 0.00075 γ estradiol. Moreover, in the application of this method for comparative study of estrogen excreted into urine, it has been found that the use of urine during 12 hours at night is simpler and more adequate. 2) As for the average estrogen quantity, cases with uterine cancer tend to show an increase as compared with that in non-cancer cases; in comparing solely the cases with cervical cancer the quantity likewise tends to show an increase in contrast with non-cancer cases; and in the cases with cervical cancer at various progressive stages it has been observed that the further advanced the cancer the greater tends to be the estrogen excreted in urine. 3) Among the patients with cervical cancer, only 17.6 per cent showed a marked abnormality in estrogen as compared with non-cancer cases; and the majority of them showed estrogen distribution within the range of that in non-cancer cases. 4) Excepting these abnormally increased cases, and designating those that clearly surpassed the average of estrogen content over the control (non-cancer group) as a relatively increased group, the rate of incidence of this relatively-increased group is higher in the cases with cervical cancer than that in the control; and the rate of such incidence is higher in a more advanced case. 5) However, even in the cases of cervical cancers in stage Ⅱ and stage Ⅲ, there were some cases showing about the same proportion of relatively low quantity of estrogen as in the control; and these results rather coincided accidentally with those of disturbances observable in the liver function in the cervical cancer as already reported in the literature. In addition, in a single case in which the quantity of estrogen has been possible to compare with histological findings of ovarian lesions, as no appreciable decrease in estrogen quantity can be observed in comparison with the findings of ovarian lesions, it is assumed that the causative factor for estrogen increment exists outside the ovarian lesions. As for the causative factor the functions of the liver and of the adrenal cortex seem to play important role. However, as can be assumed from the results of experiments so far described, the disturbances in the liver functions appear to play a principal role in elevating the quantity of active estrogen in urine of cervical cancer patient. 6) As regards the relationship between the pattern of cancer growth and the size of visible part of carcinogenic focus on one hand and the quantity of estrogen on the other, there is nothing especially noteworthy to mention. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 86 9-10 1974 口蓋裂患者の言語治療における発音補助装置（Speech aid）の応用に関する臨床的研究 415 444 EN Hiroaki Fujiwara I conducted clinical studies on application of the speech aid for the purpose of improving nasopharyngeal function in those patients who still had speech disturbance due to nasopharyngeal insufficiency even after palatal repair. For the treatment of speech disturbance accompanying cleft palate, it is necessary to perform palatal repair to restore nasopharyngeal function to its normal level as early as possible and also to give systematic speech therapy. However, we encounter not infrequently cases with residual speech difficulty due to nasopharyngeal insufficiency even after such palatal repair. For this reason, I carried out clinical studies on 64 cases by applying the speech aid in order to improve their nasopharyngeal function and giving speech therapy. As a result I have drawn the conclusions as follows. 1. For the improvement of nasopharyngeal function and normalization of speech, the speech aid seemed to be indicated for those those patients with expiration loss rate of over 2.1 at the time of blowing with Taguchi's manometer. 2. When the speech aid applied was classified into four types according to the morphology and function of its palatomaxillar section, there were 36 cases (56.2% ) for whom the palatomaxillar section was used for the sole purpose of supporting the pharyngeal section, but in the cases of bilateral and unilateral cleft lip and palate patients there were 63.4% of them for whom speech aid was used for restore the tooth defect and hard palate perforation. 3. Among 29 cases whose cephalometric x-ray films were taken at the time of pronouncing the vowel "a", the cases showing Passavant's bar amounted to 66.5% , where the upper margin of Passavant's bar was in contact with the posterior inferior edge of the pharyngeal section, which coincided with the produced under the direct view of mirror, but in those cases not revealing Passavant's bar there could be observed no definite position-relationship. 4. With growth of the jaw the speech aid applied in 3-5 year old children had to be reconstructed in the majority of cases, and the duration of time from the first speech aid insertion to the first reconstruction set ranged 19 months to 23 months. 5. The speech aid proved to bo effective on nasopharyngeal function in 85.9% of the cases applied, bringing up the respiration loss to O point at the blowing time, which in the majority of them had been attained within 4 months after the application of speech aid. Especially marked was such an effect in those cases whose palato-pharyngeal sphincter function before the application was good, some even showing an immediate effect. 6. As to the speech improvement after the application of speech aid, there were 41.7% , of the cases recovering to normal speech level (degree one), and 22.9% of them who could carry on normal speech (degree two), revealing the application to be most effective in the age range of 3 to 6 years old. 7. As for the relation of speech improvement to repiration loss rate, in the cases whose respiration loss rate recovered to O after the application of speech aid there were 48.8% whose speech improvement reached degree one and 26.8% of them degree two, but in all those whose respiration loss rate did not recover to O, there was recognized a residual cleft palate speech (degree 3) that existed prior to the application of speech aid. 8. After the application of speech aid it required a speech therapy suitable to each individual in a narrow sence for a certain length of time, and most of the patients over one year old but under two years had to be given speech therapy. 9. There were some cases of auditory disturbance with slight hearing difficulty that seemed to affect the speech recovery, hence cases with auditory disturbance require oto-rhinologic therapy. 10. It had been shown that the application of speech aid inhibits speech recovery effect in the cases of markedly low intelligence so that the speech aid was preferably indicated for those with intelligence of over (IQ=80). 11. Factors contributing to the interference of speech recovery were mental disturbance, auditory disturbance and poor family environments, and it is essential to discover the most suitable methods to eradicate these factors or to develop speech therapy most suitable for individual cases. 12. In the cases of unoperated submucous cleft palate, speech aid proved to be effective, for those cases of relatively young age with a good palato-pharyngeal sphineter function. 13. We tried adjustments of speech such as reduction of pharyngeal section by scraping on 20 cases whose speech had recovered to normal, and we found 5 cases whose speech aid could be removed, 8 cases whose pharyngeal section had shrunken, and 7 cases whose one could not be reduced in size. 14. The cases removed of speech aid were lower aged-children and had the good function of the palato-pharyngeal sphincter and the sufficient length of soft palate, and by the age of 7 years both the anterior to posterior diameter and the left-to-right diameter of the pharyngeal section had shrunken to 5 or 6mm and they showed the shrinkage rate of less than 1/2 in comparing that before and after scraping. Macroscopic examinations of these cases revealed the enhancement of the palato-pharyngeal sphincter function, especially marked was the functional improvement of the pharyngeal lateral wall in the majority of cases. In addition, the cephalometric x-ray films showed an improved movement of soft palate, a marked Passavant's bar, and the shortening of the minimum distance between the soft palate and Passavant's bar. 15. From these findings it seemed that in order to achieve the most ideal result with speech aid we should plant to restore speech level to its normal at first with speech aid, then to scrape the pharyngeal section gradually while observing patient's speech manner, and finally to try to remove the speech aid as soon as feasible. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 121 3 2009 多角的アプローチにより癌性疼痛のコントロールを得ることができた非小細胞肺癌の一例 173 175 EN Eiki Ichihara Junji Matsuoka Nagio Takigawa Takashi Matsuzaki Kuniaki Katsui Katsuyuki Kiura Mitsune Tanimoto We report a case of cancer-related pain relieved by a polyhedral approach. A woman in her late 30s with advanced non small cell lung cancer suffered from back pain caused by the cancer invasion to a thoracic vertebra. She could not take a sufficient dose of opioid due to its adverse effects. A supplementary analgesic was not found to be effective. Palliative radiation was considered desirable, but she could not maintain a dorsal position for irradiation due to back pain. Continuous epidural anesthesia was then introduced. Epidural anesthesia allowed her to lie in a spine position for radiation therapy. After completion of radiation therapy, her back pain was relieved with a low dose of transdermal fentanyl without epidural anesthesia. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 93 3-4 1981 Frank誘導法の胸部電極の位置に関する研究 第2編 臨床的検討 327 341 EN Minoru Miyasaka Vectorcardiograms with the Frank lead system were recorded in 122 healthy subjects (65 men, 57 women) and the effect of horizontal displacement of chest electrodes C, A and I on the vectorcardiogram was studied. The results obtained were as follows: 1) With electrode C displaced 2 cm to the right of the original position, Rz, Sz, and Tz increased, the azimuthal angle of QRSmax deviated backward and the QRS-T angle increased. Almost contrary changes were observed with displacement 2 cm to the left. 2) Rx, Tx, QRSmax and Tmax increased with simultaneous forward dislocation of electrodes A and I, but decreased with backward displacement of the electrodes. A greater influence on the direction of vectors was caused by shifting the electrodes backward. However, the elevation of QRSmax, the azimuthal angle of Tmax and spatial QRS-T angle changed slightly. 3) Changes greater than 1.0 mV and 10 % in one of the parameters (Rx, Rz, Sx, QRSmax, Tx, Tz, Tmax) were observed in 35-45 % of the subjects with a 2 cm horizontal displacement of electrode C, while an identical displacement of electrodes A and/or I caused the changes in more than 80 % of the subjects. 4) Therefore, in clinical use, it is acceptable to vary the position of electrode C horizontally within 1 cm from the original position in man and within 2 cm in women. No potential conflict of interest relevant to this article was reported.

岡山大学工学部 Acta Medica Okayama 0475-0071 1 1 1966 State of Efflux of Scavenging Air through the Scavenging Ports 13 22 EN 10.18926/15538 In order to make clear how the efflux angle changes in a small crankcase scavenged engine cylinder and in a large loop scavenged engine cylinder, the inlet flow pattern in the single cycle model cylinder has been observed by a high speed motion camera. In general, the scavenging air stream is not effluent in the designed direction of the scavenging port at comparatively slight opening, and the efflux angle changes in proportion to port opening advance. In a small crankcase scavenged engine cylinder, to keep the scavenging air stream in the direction of the scavenging port it is effective to incline the scavenging air passage between the crankcase and the cylinder, and to make thicker the cylinder wall where located scavenging port. In a large loop scavenged engine cylinder to coincide the scavenging air stream with the direction of the scavenging port in the early stage of the scavenging, it has an effect to set the guide plate the position of 1/2 at port height. No potential conflict of interest relevant to this article was reported.

Faculty of Engineering, Okayama University Acta Medica Okayama 0475-0071 26 2 1992 A Beam Focusing Antenna for the TE(0)n Mode High-Power Millimeter Wave 77 92 EN Osami Wada 10.18926/15439 This paper describes a method to design an antenna to focus millimeter-wave beam generated by a gyrotron. The antenna, which has been proposed by the authors, consists of a stair-cut circular waveguide and two cylindrical reflectors; one is elliptic and the other is parabolic. Its principle is based on the geometrical optics though slightly modified to consider the diffraction effect. Results of low-power experiments agree well with the design on beam direction, beam width and the position of the focal point. At 35.5 GHz using TE(01) mode, a focused beam with half-power thickness of 13 mm x 10 mm was obtained. This type of antennas find applications to millimeter-wave scattering measurement in fusion plasma research and high- energy-density source for material heating. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 104 5-6 1992 Ⅲ, Ⅳ期糖尿病性腎症の改善における腎血行動態に関する研究 601 608 EN Ken Ichiki Diabetic nephropathy is characterized by specific morphological changes and impairment of renal hemodynamics. To determine whether diabetic nephripathy could be improved by improvement of renal hemodynamics, 80μg/day of prostaglandin E(1) (PGE(1)) was administered daily for 4 weeks to 19 non-insulin-dependent diabetic inpatients with overt proteinuria. In 6 patients who initialy had daily urinary protein (UP) values above 3.5g/day, the UP value was sinificantly reduced by PGE(1) administration (p<0.05). However, in 6 patients who initially had UP values above 200mg/day and below 3.5g/day, the UP value was unchanged. In the former group, creatinine clearance was significantly reduced during PGE(1) administration (p<0.05), but was restored after termination of PGE1 adminstration (ns). Serum creatinine, serum total protein and serum albumin values were unchanged by PGE(1) administration in both groups. One petient who had a UP level above 200mg/day showed marked improvement on his renogram during PGE(1) administration and in 7 patiests who had UP values below 200mg/day, the ratio of plasma renin activity 120 minutes after furosemide injection in an upright posture to that of basal condition (PRA120/0) was significantly reduced. These findings inducate that PGE(1) increased renal blood flow, and suggest that improvement of renal hemodynamics is an important method of therapy for diabetic nephropathy with overt proteinuria. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 103 1-2 1991 Deafferentation pain に対する脳深部刺激療法の研究 第2編― 内側毛帯系刺激における除痛点の脳深部知覚誘発反応（SEP）による評価について― 147 159 EN Susumu Tomita To relieve deafferentation pain, electrophysiological assessment of target points was performed using deep cerebral SEPs. As a preliminary experiment, the relationship between the waveform of the SEP and the anatomical structure of the brain was examined in cats. The infraorbital nerve was stimulated and the SEP was recorede around the VPM. From the rostral edge of the medial leminiscus (ML), a high voltage positive wave was recorded, and from the ventral side of the VPM a wide negative wave with positive wavelets was recorded. For the treatment of three cases of thalamic pain, the deep cerebral SEP was recorded during the insertion of a chronic electrode for deep brain stimulation. By contralateral median nerve stimulation, the high voltage posotive waves (peak latency ; 13-15msec) from the ML and the subsequent unerven waves from the VPL were recorded along the trajectory. The later uneven waves were composed of wide negative waves and positive wavelets, which were thought to be derived from the synaptic activity of the VPL and thalamocortical rediation, respectively. Effective pain relief was obtained at the border zone of the ventral VPL and the ML, where the characteristic waves of the VPL changed to those of the ML. The deep cerebral SEP can be used for the identification of target points electrophysiologically. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 104 9-10 1992 組織培養法を用いた肺癌の細胞生物学並びに治療に関する研究 第1編 Human Tumor Clonogenic Assay を用いた制癌剤感受性試験の検討―肺癌を中心として― 897 904 EN Nobuyasu Kishimoto The selection of a series of effective drugs for individual patients in advance of drug therapy should increase the success of cancer chemotherapy. The human tumor clonogenic assay was evaluated as a drug sensitivity test mainly in patients with lung cancer. Tumor cells from malignant pleural effusion, tumor-positive bone marrow aspirates, and tumor tissues from the primary or metastases were used as sepcimens. Prior to plating, tumor cells were exposed to 4-hydroperoxy ifosfamide, adriamycin, mitomycin C, methotrerxate, and cisplatin for one hour at graded concentrations which were achievable in man. Of 151 specimens tested, 93(62%) yielded at least 5 colonies in the control plates containing no durgs. Colony growth (≧5/plate) was seen in 80% of squamous cell carcinoma, in 73% of small cell carcinoma, in 62% of adenocarcinoma, and in 40% of large cell carcinoma. Among the 93 specimens with colony growth, 62 yielded more than 30 colonies in the control plates and were put in force for drug sensitivity testing. Of 37 instances in which the clinical response to a certain drug was examined, 34(92%) showed an in vitro-in vivo correlation, showing a true positive rate of 57% and a true negative rate of 100%. In summary, the human tumor clonogenic assay would be an excellent technique for testing the drug sensitivity of the tumor in individual patients tumor. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 104 1-2 1992 リンパ節転移を認めない大腸癌の臨床病理学的検討 51 56 EN Shigeo Shiiki Sadanori Fuchimoto Hiromi Iwagaki Hiroshi Hamada Akio Hizuta Kunzo Oirita The clinicopathologic findines and the prognosis of 154 patients without regional lymph nodes metastasis or distant metastasis (n(-)group) were compared with those in 134 patients with regional lymph nodes metastasis and without distant netastasis (n(+)group). The mean age of the n(-) group was significantly younger than that of the n(+) group (p<0.05) and there was no significant sexual preponderance. The proportion of the cases without lymphatic vessel invasion in the n(-) group was significantly higher than in the n(+) group (p<0.01). The proportion of the cases without venous invasion was significantly higher in the n(-) group than in the n(-) group (p<0.05). There was no difference in cumulative surval rate of patients in then(-) group than in the n(+) group (p<0.05). There was no difference in cumulative survial rate of patients in the n(-) group in respect to the background factors such as sex, tumor site, and venous invasion. However, the survial rate of patients whose cancer invasion was limited within the mucosa (m), submucosa (sm) and musclar propria (pm) was significantly better than that of patients who had subserosal or subadventitial penetration (ss(al)), serosal or adeventitial penetration (s(a2)) and cancer invasion adjacent organs (si(ai))(p<0.05). The survial rate of patients with lymphatic vessel invasion was significantly higher than that of patients without lymphatic vessel invasion (p<0.05). That the poor prognostic factors in n(-) colorectal cancer patients are cancer penetration to/beyond ss(al), or positive lymphatic vessal invasion. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 106 3-4 1994 ヒト骨髄間質細胞に関する研究　第2編 慢性骨髄性白血病, 骨髄異形成症候群, 再生不良性貧血におけるヒト骨髄間質細胞の増殖動態並びに細胞構成の検討 275 285 EN Toshiaki Matsuzaki Growth and composition of human bone marrow stromal cells (HBMSC) in CML, MDS and AA were studied by using modified Dexter's culture system. Growth was experssed by the percent of HBMSC at the bottom of the culture dish(% confluence) at the 1st, 2nd, 3rd and 4th week. Cells harvested at the 4th week, were identified by monoclonal antibodies (anti-fibronectin, anti-vWF, anti-CD14, anti-CD7, anti=CD4 and anti-CD8 antibodies) and oil red 0 staininig method. In normal healty individuals (NC), % confluence at the 1st, 2nd, 3rd and 4th week were 74±4%, 82±13%, 100% and 100% respectively (n=10). HBMSC were composed of 64±4% fibro-blastoid cells, 15±3% endothelial cells, 9±4% monocyte/macrophage, 3±2% fat cells, 7±3% T lymphocyte, 4±1% helper/inducer T cells and 4±1% suppressor/cytotoxic T cells, respec-tively (n=8). In CML (n=6), % confluence at each week were almost on the decrease in comparison with those in NC and the cells tended to be detached from the bottom at the 3rd and 4th weeks. The composition of the HBMSC were not different in comparison with those in NC. In MDS (n=4), % confluence at each week and composition of HBMSC were not different in comparison with those in NC. In 3 of the 4 AA, % confluence at each week were not different in comparison with those in NC. Fat cells were markedly increased in one of 4 cases, which clinically belonged to the severe type of AA. In the other 3 AA, the percentage of endothelial cells was increased up to 35%, 32% and 21%, respectively. The CD4/CD8 rations were not different from those in NC. These finding indicate that the pathophysiological analysis of hematological disorders should be done not only on hematopoietic stem cells but also on the hematopoietic microenvi-ronment including bone marrow stromal cells. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 106 11-12 1994 イヌ摘出交叉灌流心臓標本実験系におけるフェンタニール麻酔の影響 1105 1116 EN Kazunari Ishioka Sodium pentobarbital has been used as a representative anesthetic in the experimental system using the canine excised cross-circulated heart preparaton. In the present study, fentanyl was established as a new anesthetic in this experimental system. The mechanoenergetic effects of fentanyl on the excised heart were investigated by using the framework of Emax (the slope of the end-systolic pressure-volume relation), PVA (Pressure-volume area) and VO2 (left ventricle oxygen consumption per beat). To determine the effects of fentanyl on the support dog, the systemic arterial blood pressure, heart rate, and plasma catecholamine concentration were measured. In the excised heart, fentanyl did not change the slope of the PVA-VO2 relation. This indicated that the cardiac mechanoenergetics was not qualitatively changed by fentanyl. In the support dog, fentanyl decreased the heart rate, but did not change the systemic arterial blood pressure. Fentanyl anesthesia is considered to be useful as an anesthetic for the experimantal system using the canine excised cross-circulated heart preparation. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 105 7-8 1993 PCR-RFLP 法による HLA-DNA-DQ タイピングと腎移植 715 731 EN Keiichi Hirakawa Two methods of HLA-DNA typing (PCR-RFLP method and PCR-SSO method) were performed on HLA-DQ in living related, living unrelated and cadaveric renal transplants. These two DNA typing methods allowed more accurate and more detailed typing than the conventional typing method. The effect of DNA histocompatibility of DQA 1 and DQB 1, both typed by the PCR-RFLP method, on clinical outcome and surviving graft rate of renal transplant patients was analyzed. There was no correlation found between the number of mismatches between donor and recipient of DQA 1 typing in cadaveric renal transplants, of DQB 1 typing in cadaveric, living unrelated and living related transplants and the clinical outcome nor the surviving graft rate of renal transplant patients. Both the clinical outcome and the surviving graft rate in the group in which DQ 5 mismatch between donor and recipient was positive were statistically poorer than that in the group in which DQ 5 mismatch was negative. This result suggests the existance of DQ 5 mismatch between donor and recipient greatly influences graft survival after renal transplantation. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 106 1-2 1994 気管支喘息におけるInterleukin-2 receptorに関する研究 71 81 EN Akiko Kozuka Cytokine-mediated interactions among blood cells, especially T-lymphoctes, may be impor-tant in the regulation of airway inflammation in asthma. To investigate whether T-lymphocytes are related to disease activity in asthma, serum soluble interleukin-2 receptor (sIL-2R) levels were measured in 77 bronchial asthmatics and 19 healthy volunteers. The serum sIL-2R level was higher in asthmatics than in healthy controls (mean±SD ；449.8±225.5 vs. 323.2±123.9 U/ml ; p<0.01). However, sIL-2R levels were similar between atopic and non-atopic asthmatics (451.9±235.9 vs. 416.7±147.2 U/ml), and were also similar between severe and mild to moderate asthmatics (437.4±209.9 vs. 469.8±276.1 U.ml). Steroid-dependent intractable asthmatics treated with prednisolone st doses of 5-10 mg/day showd higher sIL-2R levels (470.1±257.9 U/ml) than asthmatics treated with the drug at doses below 5 mg/day (357.2±102.6 U/ml) and intractable asthmatics treated with the drug at doses above 10 mg/day (282.5±194.5 U/ml). There was a strong correlation (r=0.915 ; p<0.01) between percentage at IL-2R-positive helper T cells among peripheral white blood cells and the serum concentration of sIL-2R. The type Ⅳ cell-mediated immune response is considered to be related to the pathogenesis of asthman. Serum sIL-2R levels are thought to reflect the extent of T-lymphocyte activation in non-malignant disease, but the level is aiso influenced by steroid therapy. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 108 1-2 1996 腫瘍内浸潤リンパ球の rIL-2 添加培養と細胞傷害活性の研究 13 29 EN Mitsuaki Matsumoto Tumor infiltrating lymohocytes (TIL) were isolated from various human cancers and cultured. The expansion, cytotoxicity, phenotype, and perforin, which is considered the cytotoxic factor of killer cells, of TIL were examinel. TIL cultured in 1000u/ml recombinant interleukin-2 (rIL-2) with 20% conditioned medium (CoM) exhibited far better expansion capability than that of TIL cultured in rIL-2 1000u/ml alone, and continued to expand up to 14 weeks. The maximal expansion index (EI) was 23912. When TIL arrested expansion during the culture, the addition of PHA restored the ability to expand. The CoM was composed of spent medium from a 3-day culture of peripheral blood mononuclear cells from cancer patients. The lymphokine-activated killer (LAK) cells induced by the culture was utilized for clinical adoptive immunotherapy in our department. Cytotoxicity against K562 and Daudi target cells was highest at 2 to 3 weeks, and disappeared between 4 and 7 weeks of culture. The phenotype of fresh TIL was mainly CD3(+) T cells, predominantly CD4(+) cells, but CD8(+) cells became predominant in long term culture. The frequency of IL-2R(+) and HLA-DR+ cells was correlated with the expansiveness of TIL. The appearance and intensity of perforin positive cells were associated with the level of cytotoxicity of cultured TIL. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 114 2 2002 B型急性肝炎における HBc 抗原特異的リンパ球反応の解析 153 158 EN Takahiro Suzuki Antigen specific T-cell responeses are important for the eradication of Hepatitis B virus (HBV) in acute infection. Flow cytometric analysis of intracellular cytokines is a simple method for studying the T-cell response at the single-cell level in a short period pf time. In the present syudy, we invesfisated the hepatitis B virus (HBV)-specific T-cell response using flow cytometry. Eight patients with acute hepatitis B and 2 patients with fulminant hepatitis B were studied. Heparinized peripheral blood was incubated with recombinant HB core antigen (HBcAg), and intracytoplasmic cytokines were analyzed by flow cytometry. HBcAg-specific interferon-gamma positive CD4 T-cella were positive in 4 of 10 patients while HBcAg-specific interferon-gamma positive CD8 T-cells and interleukin-4 positive T-cells were negatiive in all patients. No intracytoplasmic cytokines were demonstrated in healthy subjects or with recombinant hepatitis C virus (HCV) antigens. HBcAg-specific CD4 T-cells could be detected by a sensitive flow cytometric analysis of the peripherad blood and the cytokine profile of these cells was Th1. These results suggest that HBcAg-specific Th1-type CD4 T-cells may play an important role in controlling viral clearance during acute HBV infection. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 114 1 2002 Caveolin-1プロモーターを用いたHerpes Simplex Virus-thymidine kinase遺伝子発現アデノウィルスによる前立腺癌遺伝子治療における有効性と安全性の検討 27 37 EN Shin Ebara The efficacy and toxicity of adenoviral vectors that express Herpes Simplex Virus-thymidine kinase (HSV-tk) gene under the transcriptional control of caveolin-1 promoter (cav.-1-tk) was compared to Cytomegalovirus (CMV) promoter or Rous sarcoma virus (RSV) promoter HSV-tk for prostate cancer. The cav.-1-tk demonstrated the strong cytotoxicity in vitro for mouse human prostate cancer cell line (178BMA) and human prostate cancer cell line (PC-3), which overxpress caveolin-1 levels. On the other hand, the cytotoxicity was weak for mouse (178PA) and human (LNCaP) prostate cancer cell line, which express low caveolin-1 levels. The antitumor efficacy was observed in each vector in vivo orthotopic model using 178BMA prostate cancer cell line. The immunohistochemical analysis results indicated that not only cancer cells but also tumor vasculature were destroyed by cav.-1-tk. The serum AST levels of cav.-1-tk was minimal change following intravenous injection. Taken together, adenovirus-mediated HSV-tk in situ gene therapy under the transcriptional control of caveolin-1 promoter may be effective and safe for prostate cancer compared to CMV or RSV promoter HSV-tk adenoviral vectors. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 115 2 2005 先天性股関節脱臼に対する overhead traction 法の効果―大腿骨頭に位置および関節唇形態の変化― 101 108 EN Kazumi Matsuda The role of overhead traction in the treatment of development al dislocation of the hip, using two-directional srthrography before and after overhead traction,in 56 hips (47 patients) was investigated. There were 5 males (6 hips) and 42 females (50 hips). Of the 56 hips, 41 were treated before walking age and 15 after walking age. The age at the time of overhead traction ranged from 5 to 22 months (average 9 months). Mau'soriginal traction method was used in 38 hips from 1974 to 1988 and Ishida's modified method in 18 hips from 1989 to 2000, but the results were poorer with the former method. Reduction of the femoral head was considered to be obtained when it moved to the entrance of the acetabulum after overhead traction (19 of 41 hips). The shapes of the anterior and posterior portions of the limbus were corrected in 8 of 52 hips, especially in the cases treated before walking age. The superior portion of the linbus was uncharnged. According to the appearance on images, modifind overhead traction appeared to be effective in achieving reduction, but could not comoletely correct the limbus shape. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 117 2 2005 ペンシル型CCD 生体顕微鏡システムを用いたin vivo肺微小循環と肺胞呼吸の同時可視化 119 125 EN Taro Morimoto We succeeded in visualizing in vivo perialveolar microcirculation and individual alveolar respiration in rats,by our high resolution intravital charge-coupled device videomicroscopy system. To elucidate the relevance and usefullness of our methods, we investigated their behavior 1) under control conditions, 2) during increased tidal volumes (TV), 3)during positive-end expiratory pressure (PEEP) application, and 4)during exposure to hypoxia. We recognized a sheet-like flow pattern in capillaries, and observed semi-collapsed capillaries at end-inspiration while flow continued.The latter indicate existence of“vascular waterfall phenomenon”.When TV was increased from 2.5 to 5ml, the alveolar size was increased from 30±10 to 65±18μm (n＝21, p＜0.05), and the red blood cell velocities in perialveolar capillary were significantly decreased from 910±210 to 290±140μm/sec (n＝21,p＜0.05). Following PEEP application with TV of 5ml,the alveolar diameter was increased even more to 80±20μm (n＝12,p＜0.05)and the flows of microvessels stopped temporarily at end-inspiration.We also visualized that precapillary arterioles clearly constricted from 34±6 to 28±6μm in response to hypoxia (n＝9, p＜0.05). In conclusion, the intravital pencil lens-probe videomicroscopy can be a powerful tool for in vivo observation of perialveolar microcirculation and alveolar respiration under important physiological conditions such as changing TV, application of PEEP, and exposure to hypoxia. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2007 A prospective study of clinical symptoms and skin test reactions in medical students exposed to formaldehyde gas EN Sachiko Takahashi Previous investigators have reported the occurrence of both allergic and non-allergic systemic complications due to exposure to formaldehyde gas. However, little is known about the pathogenic link between formaldehyde-induced clinical symptoms and patch test results, or about the long-term effects of formaldehyde exposure. In the present study, a questionnaire was administered to 143 medical students, and 60 of them were tested by patch test for formaldehyde at the beginning and end of a human anatomy laboratory course. Another group of 76 students who had finished the course 2-4 years previously were administered another questionnaire, and the patch test was carried out on 58 of them. The frequencies of skin irritation, eye soreness, lacrimation, eye fatigue, rhinorrhea, throat irritation, general fatigue and mood swings increased after repeated exposure. Two (3.3%) of 60 students became positive to 1% formaldehyde at the end of the anatomy course (one male with allergic hand dermatitis due to direct contact with formaldehyde, and one female with an atopic background with unbearable physical symptoms) while the remaining 58 showed a negative reaction throughout the study period. The vast majority of students complained of various non-allergic, physical symptoms, and recovered from such symptoms without subsequent complications. No progression to multiple chemical sensitivity was found. Students with an episode of atopic dermatitis and allergic rhinitis were susceptible to formaldehyde exposure, and developed mucocutaneous symptoms, probably due to the impaired barrier function and remodeling of the skin and mucosa. No potential conflict of interest relevant to this article was reported.