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Two distinct human papillomavirus (HPV) DNAs (MY-1 and MY-2) were molecularly cloned from the benign skin lesions of a patient with epidermodysplasia verruciformis. The restriction map of MY-1 was the same as that of HPV 3a. The map of MY-2 appeared to be different from those of any HPVs reported in the literature. MY-2 did not cross-hybridize with MY-1 or the DNAs of HPV types 1, 2 and 4 under stringent conditions.

The direct determination by gas chromatography of blood levels of anesthetic agents has been difficult because of the water content of blood. In the present study, the method of Yokota et al. (1967) was modified by improving the packing materials of the column, the blood sample vaporizer and the flow-path during analysis. As a result, accurate and reproducible determination of halothane, enflurane and isoflurane dissolved in blood was achieved. With this system, blood in which halothane, enflurane and isoflurane had been dissolved could be analyzed without changing the column between samples. Moreover, each sample was prepared in less than 10 min, and more than 100 consecutive determinations could be made with excellent reproducibility. The coefficient of variation was less than 3.8%.

Phalloidin, a toxin from the plant Amanita phalloides, irreversibly polymerizes actin filaments and causes cholestasis. Three-dimensional structural changes induced by phalloidin in the bile canaliculi and the intra-acinar localization of these changes were studied in the rat liver by scanning and transmission electron microscopy. After 3 days of treatment, canalicular changes appeared mainly in zones 2 and 3 of Rappaport's acinus, but after 7 days of treatment changes occurred in bile canaliculi of the whole acinus. The changes in the bile canaliculi included tortuosity, saccular dilatation, loss of microvilli, bleb formation and elongation of canalicular side branches. Some side branches extended near to Disse's space, leaving only a thin cytoplasmic rim between the canalicular lumen and Disse's space. Kupffer cells were occasionally situated near such extended bile canaliculi and protruded their processes into the hepatic cord. These results suggest that bile canaliculi in zone 3 are more susceptible to phalloidin toxicity than those in zone 1 and that biliary constituents may leak from such altered bile canaliculi.

To clarify the mode of secretion of specific atrial granules, rat atrial muscle cells were examined by transmission electron microscopy. Atrial granule formation and exocytotic features of granules were clearly seen. Abrupt breaks in the unit membrane structure of mature granules were observed in thin sections, but these breaks were not detected in freeze-fracture replicas. These findings support the concept that the granule contents are released to the extracellular space by exocytosis.

The cytoskeletons of two established chick embryo cell (CEC) lines were examined by fluorescence and electron microscopy and compared with those of control cells and cells transformed by Rous sarcoma virus (RSV). In normal CEC, many stress fibers were observed. On the other hand, stress fibers were disorganized in nontransformed spontaneously established CEC, non-tumorigenic CEC partially transformed with a chemical carcinogen, and tumorigenic RSV-transformed CEC. In the normal CEC, actin filaments formed several bundles along the processes of the cell. Stereo-images of the peripheral region revealed bundles of filaments which were located along the attached side to the substrate. A fine well preserved network of filaments was also observed. On the other hand, in spontaneously established, partially transformed and RSV-transformed CEC, a fine network of filaments, but no actin cables, was found. These results support previous evidence that the cytoskeletal changes themselves are not directly related to the transformation or tumorigenicity of cells.

Seasonal distribution of the birth dates of 405 pre-menopausal and 285 post-menopausal breast cancer patients was investigated in order to determine whether or not the season of their birth was related to various reproductive risk factors of breast cancer, including nulliparity, late age at first birth, early age at menarche, late age at menopause, and a history of benign breast diseases. The seasonal distributions of births were compared between groups of patients categorized according to whether they possessed each risk factor or not, separately for pre- and post-menopausal patients. Patients with the same menopausal status generally had the same seasonal distribution of births, irrespective of whether or not they possessed a risk factor. Moreover, low-risk patients exhibited more deviation in the seasonal distribution of birth from general births than the high-risk patients. These results suggest that the distinctive seasonal distribution of birth observed in breast cancer patients is basically a phenomenon independent from the effect of the reproductive history on the occurrence of breast cancer, and that specific seasonal factors are involved at the fetal or neonatal stage in the etiology of breast cancer.

The arylsulfatase activity and histamine concentration of bronchoalveolar lavage fluid (BALF) were examined in patients with bronchial asthma in relation to the eosinophil count and asthma type (atopic and non-atopic). The BALF arylsulfatase activity and histamine concentration were significantly higher in atopic asthmatics than in non-atopic asthmatics. In atopic asthmatics, the activity of arylsulfatase was significantly increased in patients with a higher eosinophil count (10% or more). However, the BALF histamine concentration did not correlate with the eosinophil count. In non-atopic asthmatics, there was no significant correlation between arylsulfatase activity and the eosinophil count. The results show that arylsulfatase participates in IgE-mediated allergic reactions.

Upper gastrointestinal bleeding is a major adverse event of non-steroidal anti-inflammatory drugs (NSAIDs), and co-administration of proton pump inhibitors and H2 receptor antagonists has been established as a means of preventing such an eff ect. However, the incidence of bleeding associated with NSAID-induced ulcers under conditions where such strong anti-acid agents are used for prevention has yet to be clarified. We aimed to determine the annual incidence of serious upper gastrointestinal ulcer bleeding among Japanese patients in whom NSAIDs were used in our hospital. Before commencing the study, we recommended to all the physicians in our hospital the best method for caring for NSAID users, focusing on the concomitant use of proton pump inhibitors or H2 receptor antagonists. We conducted a cohort study involving 17,270 patients for whom NSAIDs had been newly prescribed. Bleeding from gastric ulcers was observed in 8 of the 17,270 patients using NSAIDs (0.05%). The pooled incidence rate for bleeding was calculated as 2.65 (95% confidence interval, 2.56-2.74) and 1.29 (1.27-1.31) per 1,000 patient years for low-dose aspirin and non-aspirin NSAID users, respectively. None of the bleeding ulcer patients required blood transfusion or were in serious condition. In conclusion, gastric ulcer bleeding occurred in low-dose aspirin or non-aspirin NSAID users, but its incidence was low and outcomes were not serious when adequate preventive measures were taken.

Dry pleural dissemination in non-small cell lung cancer, defined as solid pleural metastasis of lung cancer without pleural eff usion, is a condition occurring in T4 lung cancer. Positron emission tomography (PET) has been reported to be useful for the diagnosis and staging of lung cancer. It has been reported that positive findings on PET scans of indeterminate pleural abnormalities at computed tomography (CT) are sensitive to malignancy. We encountered two cases of dry small pleural dissemination of adenocarcinoma of the lung preoperatively detected by PET/CT. A 75-year-old man and a 66-year-old man underwent CT scan, which demonstrated solitary tumor in the lung, an enlarged mediastinal lymph node, and a small pleural nodule less than 10 mm in size, all of which were positive findings on the fluorine 18 fluorodeoxyglucose (FDG) PET portion of an integrated PET/CT. Both patients underwent thoracoscopic biopsy of the dry pleural nodule revealing dissemination of adenocarcinoma of the lung (T4). Whereas histological thoracoscopic diagnosis remains mandatory before planning treatment, our cases may suggest that PET/CT will be useful as a screening modality for dry pleural dissemination of lung cancer.

Malignant mesothelioma (MM) is a highly aggressive tumor with a dismal prognosis. The incidence of MM is increasing as a result of widespread exposure to asbestos. As for the molecular alterations that occur in MM, chromosome alterations including homo-deletion of the P16 and P14 genes located in the 9p21 are well known. Mutations are rare in the P53 and Ras genes, which are frequently present in epithelial solid tumors. However, mutations are frequently present in the neurofi bromatosis type 2 gene. Epigenetic alterations including DNA methylation have been found in the MM, the profi le of which is diff erent from that of lung cancer, although differential diagnosis is sometimes clinically difficult. As in other malignant tumors, genes that are related to immortalization, proliferation, metastasis, angiogenesis, and anti-apoptosis are also overexpressed in MM, contributing to its malignant phenotype. It is of interest that simian virus 40 has been implicated to be one of the causative factors of MM in western countries. Although the causative role of asbestos is well-known in MM, much less information is available for MM than for other malignant tumors regarding the molecular alterations that occur in the disease. In terms of future tasks, it will be necessary to apply the knowledge that is learned about molecular alterations to clinical practice and to further elucidate the pathogenesis of MM with extensive research.

The induction of both long-term potentiation (LTP) and long-term depression (LTD) in the hippocampal CA1 region is triggered by the activation of N-methyl-D-aspartate (NMDA) receptors and the subsequent postsynaptic intracellular Ca2+ increase. However, how NMDA receptor activation differs between LTP and LTD induction is unclear. In the present study, we examined the eff ects of the magnitude and duration of NMDA receptor activation on the induction of LTP and LTD. Partial blockage of NMDA receptors by a low concentration of aminophosphonovaleric acid (APV)(2 μM) prevented the induction of LTP, but not LTD. In contrast, a high concentration of APV(25 μM) blocked both LTP and LTD. Tetanus stimulation-induced LTP was impaired when hippocampal slices were given the tetanus stimulation for more than 5 min. Under partial blockage of NMDA receptors, the prolonged-tetanus stimulation induced LTD but not LTP. This phenomenon was mimicked by the application of glutamate to the slices. Finally, LTD induced by prolonged activation of NMDA receptors was not aff ected by inhibition of the desensitization of α-amino-3-hydroxy-5 methylisoxazole-4-propionic acid (AMPA) receptors. These results suggest that critical diff erences exist between the induction of LTP and that of LTD in terms of both the magnitude and the duration of NMDA receptor activation. The duration of the increase in intracellular Ca2+ concentration may be critical for determining whether LTP or LTD induction occurs.

Since clinical document architecture (CDA) became an American National Standards Institute (ANSI)-approved health level seven (HL7) Standard, many countries have begun making an eff ort to make local standards conform to CDA. In order to make CDA compatible with the many diff erent local standards existing in diff erent countries, we designed a prototype model using HL7 CDA R2 with medical markup language (MML), a Japanese medical data exchange standard. Furthermore, a referral letter system based on this model was developed. Archetypes were used to express medical concepts in a formal manner and to make 2 diff erent standards work collaboratively. We share herein the experience gathered in designing and implementing a referral letter system based on HL7 CDA, Release 2 (CDA R2). We also outline the challenges encountered in our project and the opportunities to widen the scope of this approach to other clinical documents.

Dental reconstruction in the cleft space is difficult in some patients with cleft lip and palate because of oronasal fistulas. Most of these patients receive a particle cancellous bone marrow (PCBM) graft to close the alveolar cleft, and secondary bone grafting is also required. Treatment options for the alveolar cleft including fixed or removable prostheses require the preparation of healthy teeth and are associated with functional or social difficulties. Recently, the effectiveness of dental implant treatment for cleft lip and palate patients has been reported. However, there have been few reports on the use of this treatment in bilateral cleft lip and palate patients. We report the case of a patient who had bilateral cleft lip and palate and was missing both lateral incisors. She received dental implant treatment after a PCBM graft and ramus bone onlay grafting (RBOG). A 34-month postoperative course was uneventful.

From January 2004 to March 2007, 308 patients with clinically localized prostate cancer were treated using iodine-125 (125I) seed implantation (permanent brachytherapy) at Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences. We evaluated the treatment’s effi cacy and morbidity in 300 prostate cancer patients who were followed up for more than 1 month after brachytherapy. Based on the National Comprehensive Cancer Network (NCCN) guidelines, patients with a prostate volume of less than 40 ml in transrectal ultrasound imaging were classifi ed as low or intermediate risk. The median patient age was 67 years (range 50 to 79 years), the median prostate-specific antigen (PSA) value before biopsy was 6.95 ng/ml (range 1.13 to 24.7 ng/ml), and the median prostate volume was 24.33 ml (range 9.3 to 41.76 ml). The median follow-up was 18 months (range 1 to 36 months) and the PSA levels decreased in almost all patients after brachytherapy. Although 194 of 300 patients (64.7%) complained of diffi culty in urination, pollakisuria/urgency, miction pain, and/or urinary incontinence, all of which might be associated with radiation prostatitis during the fi rst month after brachytherapy, these symptoms gradually improved. 125I seed implantation brachytherapy is safe and eff ective for localized prostate cancer within short-term follow up.

We analyzed nucleotide changes in 3 genes, ARIX, PHOX2B, and KIF21A, in 6 patients of 3 families with congenital superior oblique muscle palsy. Three exons of ARIX, 3 exons of PHOX2B, and exons 8, 20, and 21 of KIF21A were amplified by polymerase chain reaction from genomic DNA isolated from the peripheral blood. The DNA fragments were directly sequenced in both directions. In 2 different families, a heterozygous nucleotide change, ARIX 153G>A, in the 5’-untranslated region was found in common between a father and daughter with muscle palsy and between a mother and daughter with muscle palsy (Family No. 1 and No. 3). In the other family (Family No. 2), a heterozygous 15-nucleotide deletion, PHOX2B 1124del15, resulting in loss of 5 alanine residues in the alanine repeat of the protein, was found in the daughter with muscle palsy and her father with normal traits, but was not found in the mother with muscle palsy. No KIF21A nucleotide change was found in any patients. The ARIX 153G>A polymorphism might be a genetic risk factor for the development of congenital superior oblique muscle palsy.

We defined the maximum-tolerated dose (MTD) of chemoradiotherapy (cisplatin (CDDP) with 5-fluorouracil (5-FU) and concurrent chemoradiotherapy) for Chinese patients with esophageal cancer. Twenty-one previously untreated patients with primary esophageal cancer were entered into this study. Escalating doses of CDDP with 5-FU were administered in a modified Fibonacci sequence, with concurrent conventional fractionation radiotherapy (CFR) of 60 Gy or 50 Gy. The starting doses were CDDP 37.5 mg/m2 on day 1, and 5-FU 500 mg/m2 on days 1-5, respectively. The regimen was repeated 4 times every 28 days. If no dose-limiting toxicity (DLT) was observed, the next dose level was applied. The procedures were repeated until DLT appeared. The MTD was declared to be 1 dose level below the level at which DLT appeared. DLT was grade 3 radiation-induced esophagitis at a dose level of CDDP 60 mg/m2 with 5-FU 700 mg/m2 and concurrent 60 Gy CFR. MTD was defined as CDDP 52.5 mg/m2 with 5-FU 700 mg/m2 and concurrent 50 Gy CFR. The MTD of CDDP with 5-FU and in concurrent chemoradiotherapy for Chinese patients with esophageal cancer is CDDP 52.5 mg/m2 on day 1 and 5FU 700 mg/m2 on days 1-5, repeated 4 times every 28 days, and concurrent 50 Gy CFR. Further evaluation of this regimen in a prospective phase II trial is ongoing.

Although the identification and characterisation of a participant's lateral profile during quiet standing have not received much research attention, they have the potential to greatly extend our understanding of upright stance stability control. This study further examines limb load asymmetries during quiet bipedal stance. During voluntary frontal-plane weight shifting for 2 min, 300 centre-of-pressure displacements on 14 blindfolded right-handed young adults were recorded. Four biomechanical indices were used to assess postural behaviour. These were the bias of time and the magnitude of the partial ground reaction forces from both legs, and the bias in the number and magnitude of microshifts influencing stability. Our study identifies a significant level of asymmetry in the quiet bipedal stance of right-handed people. This asymmetry is associated with the right-sided bias of the ground reaction force and the angle of inclination to the upright (vertical) centroidal line. We found that the initial lateralisation of the partial ground reaction forces from both feet, as well as the period of ground reaction force bias, are important elements in any clinical tests involving quiet bipedal stance.

Narrow-band imaging (NBI) is a novel optical technique that uses narrow bandwidth filters in a video endoscope system to improve the diagnostic capability of endoscopes in characterizing tissues. It is well known that early identification of neoplasia in the gastrointestinal tract using this technique might make it possible to reduce the suffering of patients caused by loss of function or severe complications after radical surgery. Several reports have introduced this system as a preoperative examination to evaluate the lateral spread of the neoplastic lesions in the oropharynx or hypopharynx. We experienced a case with hypopharyngeal cancer in which we were able to avoid underestimating cancer lesions following insufficient resection using the NBI system. A 62-year-old female underwent partial hypopharyngectomy with the margin estimated by an NBI view coupled with reconstruction of the hypopharynx while preserving the larynx. The resected specimen was cut into serial sections for a detailed pathology examination. The surgical margin seemed to be wide enough and it could be assumed that if possible we should observe these cancers with conventional electroendoscopy and NBI before treatment.

Between January 2001 and December 2007, we performed vaginoplasty as sex reassignment surgery in a total of 14 male-to-female transsexual (MTFTS) patients [1]. Several complications occurred such as partial flap necrosis, rectovaginal fistula formation and hypersensitivity of the neoclitoris. Just after the operation, some patients feel that their penises still exist, but by several weeks postoperatively, this sensation has disappeared. Herein we report a case of MTFTS in whom the sensation of a phantom erectile penis persisted for much longer.

Oxidative stress, including the reactive oxygen or nitrogen species generated in the enzymatical oxidationor auto-oxidation of an excess amount of dopamine, is thought to play an important role in dopaminergic neurotoxicity. Dopamine and its metabolites containing 2 hydroxyl residues exert cytotoxicityin dopaminergic neuronal cells, primarily due to the generation of highly reactive dopamine and DOPA quinones. Dopamine and DOPA quinones may irreversibly alter protein function through the formation of 5-cysteinyl-catechols on the proteins. Furthermore, the quinone formation is closely linked to other representative hypotheses such as mitochondrial dysfunction, inflammation, oxidative stress, and dysfunction of the ubiquitin-proteasome system, in the pathogenesis of neurodegenerative diseases. Therefore, pathogenic effects of the dopamine quinone have recently focused on dopaminergicneuron-specific oxidative stress. In this article, we primarily review recent studies on the pathogenicity of quinone formation, in addition to several neuroprotective approaches against dopaminequinone-induced dysfunction of dopaminergic neurons.