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The development of useful therapy for intraabdominal carcinomatosis originating from gastrointestinal cancer is an important theme in cancer therapy. We developed recently an experimental model of intraabdominal carcinomatosis in nude mice by intraperitoneal transplantation of human colon cancer cells (RPMI 4788). Using this model, we investigated the antitumor effects of recombinant human interferon (rIFN)-beta and rIFN-gamma administered singly or in combination. Treatment was initiated 2 days after CD-1 nude mice were inoculated intraperitoneally with 5 X 10(6) RPMI 4788 cells. Intraperitoneal administration for 10 consecutive days of either rIFN-beta (2.5 X 10(5) IU/mouse/day) or rIFN-gamma (2.5 X 10(5) JRU/mouse/day) resulted in a significant prolongation of survival compared with the saline control group [survival in the control: 41.8 +/- 5.6 days (mean +/- SD)]. Combined administration of rIFN-beta and rIFN-gamma for 10 days yielded a marked synergistic effect on the prolongation of survival (114.0 +/- 8.2 days). However, combined administration of rIFN-beta and rIFN-gamma in a single dose equal to the total dose given fractionally over 10 days did not yield a synergistic effect. These results suggest that daily administration of rIFN-beta and rIFN-gamma combined may provide a highly potent antitumor effect against human peritoneal carcinomatosis.

In vitro release of atrial natriuretic peptide (ANP) from atria was examined by ANP radioimmunoassay. Isolated right rat atria were incubated in Krebs-Ringer bicarbonate buffer, and test substances were added to the incubation medium. The fluid was assayed for rat ANP by a radioimmunoassay method recently developed in our laboratory. We produced an antiserum to human ANP(99-216) (alpha-hANP(1-28)) which showed a good cross-reactivity of 63% with rat ANP(99-126) (alpha-rANP(1-28)) and was useful for measuring rat ANP concentrations of the medium. Application of the medium to a reverse phase high performance liquid chromatography (HPLC) system resulted in a single peak of immunoreactive rat ANP corresponding to a small molecular weight synthetic rat ANP of 28 amino acid residues. Catecholamines (epinephrine, norepinephrine and isoproterenol) reduced the basal secretion of ANP, whereas acetylcholine stimulated the release of ANP. Forskolin and dibutyryl cyclic AMP did not affect the release of ANP. These results suggest the possibility that the regulation of ANP release may be partially associated with adrenergic and cholinergic mechanisms.

Eradication of immunologically-syngeneic tumors was achieved by adoptive chemotherapy using effector cells induced by Corynebacterium parvum-Pyridine Extract Residue (CP-PER). A mixture of 2 X 10(6) Meth A cells and 0.1 mg CP-PER was subcutaneously inoculated into the back of donor BALB/c mice, with the result that their spleen cells showed an antitumor effect 10 to 13 days after the inoculation. These cells were used as immune cells. Recipient mice were inoculated with 1 X 10(6) Meth A cells, and 2 days later were administered cyclophosphamide. On the following day, 1 X 10(8) immune cells were adoptively transferred into the recipient mice. As a result, the tumor began to regress 7 to 12 days after the adoptive transfer. An immuno-histochemical study of the donors' spleens and the recipients' regressing tumors revealed that the ratio of L3T4+ T cells to Lyt-2+ T cells in the donors' spleens was increased and that the infiltrating cells in the recipients' tumors were mainly composed of L3T4+ T cells. This confirmed that the transfer of L3T4+ T cells led to the infiltration of L3T4+ T cells into the recipients' tumors, causing their eradication.

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.

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.

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.

We discuss the concept of social capital, which has received much attention recently. Social capital is important for the following 2 key reasons:(1) a highly democratic polity and a strong economic performance that attaches great importance to the public good can be achieved on the basis of high social capital;and (2) social capital can effect health status in the human population, and widening of income inequality harms human health through the erosion of social capital. In addition, there are 3 political implications of social capital for Japanese society:(1) social capital has implications for the political decision of whether Japanese society should adopt a “medium burden for medium welfare” or a “low burden for small welfare” model together with the concept of social overhead capital;(2) reciprocity, which is one of the primary components of social capital, is similar to the philosophy underlying the health care system of Japan;(3) Japanese society needs to change from a society that emphasizes the relationships between its members to a society that is open to outsiders and has sufficient opportunities.

In the present study, we examined the dynamic of school-health-based parasite control and the related socio-economic influences. This is an ecological study based on data from 46 prefectures in Japan. The exponential decay of Ascaris lumbricoides prevalence was calculated by iterative least-squares method. Pearsonʼs correlation and multiple linear regression model analysis were performed to assess the associations between the prevalence of Ascaris lumbricoides in Japanese school children and socio-economic variables such as the prefecture income per capita, the percentage of primary industry, the population density per 1 km2, the diffusion rate of population under water supply, and the percentage of upper secondary school enrollment. The results indicated that the parasite carrier rate was higher in younger students. The half-life of Ascaris lumbricoides prevalence was approximately 3 years with significant variation among prefectures. Multiple regression analyses showed that the decrease of infection in elementary and lower secondary school children had a significant positive association with primary industry and a significant negative association with prefecture income per capita. The school-health-based parasite intervention differs by prefecture and has changed over time according to the respective prefectural stage of economic development.

Activation of inflammatory response during cardiopulmonary bypass (CPB) may lead to considerable post-operative mortality. Recently, pentoxifylline (PTX), a methylxanthine derivative, has been reported to be effective in inhibiting proinflammatory cytokine production. This study aimed to determine whether or not PTX prevented CPB-induced systemic inflammatory response syndrome (SIRS) in patients undergoing cardiovascular surgery. Thirty adult patients were randomly separated into 2 experimental groups and 1 control group of 10 patients each. The experimental group received peroral PTX administration (Group 1: 600 mg/day, Group 2: 900 mg/day), while the control group did not. In Group 1 and Group 2, PTX administration was started on preoperative day 5 and continued for 5 days. Serum levels of PTX and IL-6 were measured just before and at 4 h after CPB using HPLC and ELISA, respectively. Respiratory index (RI) before and at 4 h after CPB was calculated, and serum levels of C-reactive protein (CRP) and fibrinogen on postoperative day 1 were also determined. There were no significant differences in age, body weight, sex, surgical procedures, CPB time, haemodynamics or risk factors among the 3 groups. Serum IL-6 level and RI index after CPB in Group 2 were significantly decreased compared with those in Group 1 and the control group. These results, therefore, suggested that preoperative daily administration of 900 mg/day PTX contributed to the attenuation of CPB-induced SIRS and had a beneficial effect on the postoperative course after cardiovascular surgery.