Unconventional s-wave superconductivity in Fe(Se,Te).

The superconducting state is characterized by a pairing of electrons with a superconducting gap on the Fermi surface. In iron-based superconductors, an unconventional pairing state has been argued for theoretically. We used scanning tunneling microscopy on Fe(Se,Te) single crystals to image the quasi-particle scattering interference patterns in the superconducting state. By applying a magnetic field to break the time-reversal symmetry, the relative sign of the superconducting gap can be determined from the magnetic-field dependence of quasi-particle scattering amplitudes. Our results indicate that the sign is reversed between the hole and the electron Fermi-surface pockets (s(+/-)-wave), favoring the unconventional pairing mechanism associated with spin fluctuations.

Influence of BMI, Age and duration of diabetes mellitus on glycaemic control with twice-daily injections of biphasic insulin aspart 30 versus multiple daily injections of insulin aspart (JDDM 18): retrospective reanalysis of a 6-month, randomized, open-label, multicentre trial in Japan.

BACKGROUND AND OBJECTIVE: Good glycaemic control in patients with diabetes mellitus often requires insulin supplementation therapy. Recent developments of analogue insulin and premixed formulations have increased the therapeutic options for patients who need such therapy. This study aimed to retrospectively clarify appropriate treatment regimens according to age, body mass index (BMI) and duration of diabetes in Japanese patients with type 2 diabetes previously entered in an open-label, randomized trial that compared convenience-oriented biphasic insulin aspart 30 versus multiple injections of insulin aspart with or without NPH insulin. METHODS: Japanese insulin-naïve patients were randomized to receive either biphasic insulin aspart 30 twice daily or insulin aspart three times daily with or without multiple injections of NPH insulin for a treatment period lasting 6 months. RESULTS: Reduction of glycosylated haemoglobin (HbA(1c)) at the end of 6 months was not different in the two treatment groups irrespective of BMI, age and duration of diabetes. However, the achievement rate of HbA(1c) <7.0% was significantly higher in patients with a BMI <25 kg/m2 in the multiple-injection group and tended to be higher in patients with a diabetes duration <10 years in the twice-daily injection group. CONCLUSION: Twice-daily injections of biphasic insulin aspart 30 may be more suitable for obese patients whereas multiple injections of insulin aspart with or without NPH insulin may be preferable for those with a longer duration of diabetes.

Augmentation of transgene expression in cold-preserved organs using vascular endothelial growth factor receptor-mediated adenoviral vector combined with hyperbaric oxygen.

Adenovirus-mediated gene transfer has been widely used in gene therapy for congenital metabolic, cardiovascular, and malignant diseases. It has been reported that a gene transfer technique into transplanted organs may suppress rejection reactions and inhibit preservation injury. However, the magnitude of transgene expression in organs preserved at a cold temperature remains to be determined. In this study, we compared the transgene expression using vascular endothelial growth factor receptor (VEGFR)-mediated adenoviral vector at cold versus warm temperatures alone and combined with hyperbaric oxygen in cold-preserved organs. The transgene expression by porcine endothelial cells transduced with adenoviral vector was significantly higher after a 24 hour-incubation at warm temperature than after a 1 hour-incubation with warm or cold temperature. Moreover, the transgene expression of after a 1-hour incubation at cold temperature was significantly lower than a 1-hour incubation at warm temperature. The VEGFR-mediated adenoviral vector augmented transgene expression during a 1-hour incubation at cold temperature compared to the control vector. A/J skin graft survival in C3H mice was significantly prolonged compared to control or standard vector with CTLA4Ig cDNA using VEGFR-mediated adenoviral vector with CTLA4Ig cDNA in a 1-hour cold preservation. Furthermore, combined use of VEGFR-mediated adenoviral vector with CTLA4Ig cDNA plus FK506 showed an augmented effect on graft prolongation. It is concluded that adenovirus-mediated gene transfer in 1-hour cold-preserved organ is difficult compared to that in the warm condition. However, VEGFR-mediated gene transfer can augment the transgene expression in 1-hour cold-preserved organs, followed by the effective suppression of rejection reactions in allogeneic transplantation.

Sequential analysis of testicular lesions and serum hormone levels in rats treated with a Psoralea corylifolia extract.

In order to clarify pathogenetic targets for the testicular toxicity of a extract of Psoralea corylifolia (P. corylifolia), F344 rats were fed diet containing 3% P. corylifolia extract for up to 12 weeks and subjected to hormone assays and histopathological examination on the testis and epididymis at weeks 1, 2, 4, 8 and 12 (Exp 1). Similar analyses were performed on 1, 3, 7 and 14 days after a single gavage administration of the P. corylifolia extract at a dose of 10 g/kg b.w. (Exp 2). In Exp 1, increase in the numbers of degenerated and exfoliated germ cells and loss of elongated spermatids beyond steps 7 or 8 were initially observed in the seminiferous tubules at week 1, followed by more pronounced degeneration of germ cells with depletion of post-meiotic populations from week 2. The tubular degeneration was associated with Leydig cell atrophy and persistent reduction of serum testosterone and FSH levels throughout the treatment period and a slight reduction of serum LH in later stages. In Exp 2, reduction of serum testosterone and FSH levels preceded degeneration of germ cells in stage VII and VIII tubules at 3 and 7 days after the administration. The results suggest that rapid androgen deprivation reflecting direct interference with Leydig cell function and simultaneous disturbance of the pituitary-testicular axis play pivotal roles in P. corylifolia extract-induced germ cell injury in seminiferous tubules.

Effect of alpha-tocopherol on hepatocarcinogenesis in transforming growth factor-alpha (TGF-alpha) transgenic mice treated with diethylnitrosamine.

To examine the potentially chemopreventive effects of alpha-tocopherol on hepatocarcinogenesis, we fed the transgenic mice line MT42, which overexpresses transforming growth factor-alpha (TGF-alpha) and which has been established as having a high incidence of liver tumor, with different concentrations of alpha-tocopherol and examined the hepatic tumorigenesis of these mice. At 3 weeks of age, MT42 male mice received a single intraperitoneal injection of diethylnitrosamine (DEN), 5 mg/kg body weight, to initiate the formation of liver tumors. The mice were divided into three groups: group A, control diet (20 mg/kg of alpha-tocopherylacetate); group B, deficient diet (less than 1 mg/kg); group C, supplemented diet (500 mg/kg). Neoplastic change was determined at 40 weeks of age. The incidence of adenomas (p < 0.05), the maximum tumor size (p < 0.01), the mean relative liver weight (p < 0.01), and the proliferating cell nuclear antigen (PCNA) labeling indices of the non-tumor sites (p < 0.01) of group B were significantly higher than those of group C. No toxic effects of alpha-tocopherol were found. Alpha-tocopherol-deficient diet accelerated the hepatocarcinogenesis of TGF-alpha transgenic mice treated with DEN. At best, these data demonstrate that alpha-tocopherol-deficiency is not beneficial for prevention of hepatocarcinogenesis in this model. Alpha-tocopherol may be useful for the chemoprevention for liver cancer.

Zinc supplementation enhances the response to interferon therapy in patients with chronic hepatitis C.

We evaluated the synergistic effect of zinc supplementation on the response to interferon (IFN) therapy in patients with intractable chronic hepatitis C in a pilot study using natural IFN-alpha with or without zinc. No clinical differences were observed between patients treated with IFN alone (n=40) and IFN with polaprezinc (IFN + Zn, n=35). All patients were positive for HCV genotype Ib and had more than 105 copies of the virus/mL serum. Ten million units of natural IFN-alpha was administered daily for 4 weeks followed by the same dose every other day for 20 weeks. In the IFN + Zn group, patients received an additional dose of 150 mg/day polaprezinc orally throughout the 24-week IFN course. No additional side-effects of polaprezinc were noted but four out of 40 IFN alone treatment and three out of 35 IFN + Zn group withdrew because of side-effects. Complete response (CR) was defined as negative HCV RNA in the serum on PCR and normal aminotransferase level 6 months after therapy. Incomplete response (IR) was normal liver enzyme and positive serum HCV RNA. Both of them were evaluated at the 6 months after the completion of the treatment. Patients with higher levels of serum HCV (more than 5 x 105 copies/mL) had little response in both treatment groups. Patients with moderate amount of HCV (105 to 4.99 x 105/mL) showed high response rates in combination group (CR: 11/27, 40.7%; CR + IR 15/27, 64.3%), better than IFN alone (CR: 2/15, 18.2%; CR + IR: 2/15, 18.2%). Serum zinc levels were higher in patients with IFN + Zn group than in the IFN group. Our results indicate that zinc supplementation enhances the response to interferon therapy in patients with intractable chronic hepatitis C.

An individual patient data meta-analysis of long supported adjuvant chemotherapy with oral carmofur in patients with curatively resected colorectal cancer.

To reappraise the benefits of the long supported chemotherapy with carmofur, a meta-analysis based on individual patient data from the three clinical trials was performed by pooling 614 patients from three trials, there is a statistically significant survival benefit (2p=0.032) and disease-free survival (DFS) benefit (2p=0.021) for carmofur; and a highly significant advantage for carmofur in DFS (2p=0.0004) and in survival (2p=0.004) in Dukes' C patients. This IPD meta-analysis strongly suggested an effect of oral carmofur in a long supported chemotherapy for curatively resected colorectal carcinoma.

[Efficacy of mesalamine enema in the treatment of steroid-resistant or dependent distal ulcerative colitis].

The efficacy and safety of mesalamine enema were examined in 20 patients with steroid-resistant or dependent, distal ulcerative colitis. Rectal bleeding disappeared in 3 (18%). 8 (50%) of 16 patients within 2 weeks and 4 weeks after the start of mesalamine enema treatment, respectively. Mean clinical activity index (CAI) score after the treatment was significantly reduced (8.1-->3.6, p < 0.001). Furthermore, Mean doses of oral corticosteroid after the treatment (7.3 mg) were also significantly lower than those before the treatment (12.8 mg) (p < 0.01). Four patients dropped out. Three patients could not retain the enemas because of abdominal discomfort and one patient had fever and rash. There were no significant differences in age, gender, disease duration, disease type, and mean doses of oral corticosteroid before the treatment between the response group (n = 8) and the non-response group (n = 8). However, clinical and endoscopic activities before mesalamine enema treatment in the non-response group (CAI 9.8, Matts score 8.0) were higher than those in the response group (CAI 6.4, Matts score 5.5). These results suggest that mesalamine enema is useful for mildly to moderately active distal ulcerative colitis by improving clinical symptoms and reducing corticosteroid.

Iron enhances hepatitis C virus replication in cultured human hepatocytes.

BACKGROUND: Iron overload in the presence of increasing concentrations of iron is one of the indicators of poor response to interferon therapy in chronic hepatitis C. In order to analyze the effect of iron on hepatitis C virus (HCV) replication, we measured replication in an HCV-infected cell line. METHODS AND RESULTS: Cells from a non-neoplastic HCV-infected human hepatocyte line (PH5CH8) susceptible to HCV infection and supportive of HCV replication were used in this study. The replication of HCV RNA was measured by reverse transcription-nested polymerase chain reaction (RT-nested PCR). PH5CH8 cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. PH5CH8 cells were incubated with 0, 1, 10, 50, and 100 microM of FeSO4 at 37 degrees C with 5% CO2. Forty-eight hours after iron supplementation, the quantity of HCV RNA in the cells incubated in 50 and 100 microM of FeSO4 was approximately ten times that of the cells with no iron supplementation. Similar changes were observed beginning at 12 h from supplementation with FeSO4 and continued for at least 72 h after supplementation. MTT assay indicated that iron did not have cytotoxic effects on the PH5CH8 cells. CONCLUSION: Iron enhances HCV replication in a hepatocyte cell line. The results suggest that iron deposition in hepatocytes could facilitate HCV infection in the liver.

Proline accumulation by mutation or disruption of the proline oxidase gene improves resistance to freezing and desiccation stresses in Saccharomyces cerevisiae.

We examined the role of intracellular proline under freezing and desiccation stress conditions in Saccharomyces cerevisiae. When cultured in liquid minimal medium, the proline-nonutilizing mutant containing the put1 mutation (proline oxidase-deficient) produced more intracellular proline, and increased the cell survival rate as compared to the wild-type strain after freezing and desiccation. We also constructed two PUT1 gene disruptants. PUT1-disrupted mutants in minimal medium supplemented with external proline at 0.1% accumulated higher proline levels than those of the control strains (17-22-fold). These disruptants also had a 2-5-fold increase in cell viability compared to the control strains after freezing and desiccation stresses. These results indicate that proline has a stress-protective function in yeast.

Optimum duration of oral adjuvant chemotherapy of HCFU for colorectal cancer; review of 5-year follow-up.

PURPOSE: To investigate the optimal duration of oral HCFU administration for minimization of side effects induced by long-term administration. PATIENTS AND METHODS: In total, 155 patients allocated to two groups of different duration of the therapy were reviewed: twice or three times per day doses of oral HCFU (8 mg/Kg body weight/day) for 3 months vs. 12 months. RESULTS: Though statistically significant difference was not found in cumulative survival and disease-free rates between the groups due to so many violations of duration of therapy, when reanalyzing the variables in order of real duration of therapy, those rates were significantly higher in patients treated for 300 and more days than less than 300 days (g-Wilcoxon test: p < 0.04). No significant difference was observed in the background factors between the groups. CONCLUSION: At least 300 days is suggested to be necessary to obtain the optimal effectiveness of adjuvant chemotherapy for curatively resected colorectal cancer.

[A 90-day repeated dose oral toxicity study of magnesium chloride in F344 rats].

In order to examine the toxicity of magnesium chloride hexahydrate, four groups of 10 male and 10 female F344 rats received the compound by dietary supplementation at 2.5, 0.5, 0.1 or 0% for 90 days. No treatment-related death was observed during the study. Transient soft stool and sustained increase in water consumption were observed both in males and females of the 2.5% group and slight reduction in body weight gain was noted in the high-dose males. There were no toxic changes in food consumption, organ weights, hematology and biochemistry, and histopathological examinations in any treated-groups. Based on these results, the no-observed-adverse-effect-level was estimated to be 0.5%, and 2.5% is considered to be appropriate as highest dose for a 2-year carcinogenicity study.

Nausea and vomiting induced by arterial chemo-embolization in patients with hepatocellular carcinoma and the antiemetic effect of ondansetron hydrochloride.

To determine the incidence of nausea and vomiting and the antiemetic effect of ondansetron hydrochloride (OND) in patients with hepatocellular carcinoma treated with arterial chemo-embolization, we studied 59 patients with hepatocellular carcinoma who were treated with transcatheter arterial embolization (TAE) or lipiodolized transcatheter arterial infusion (L-TAI). We investigated the incidence of nausea and vomiting and the amount of food intake when TAE or L-TAI was performed. All patients who experienced nausea and vomiting received OND administered prophylactically at the time of the next TAE or L-TAI to evaluate the antiemetic effect of the drug. Cumulative rates of nausea and vomiting during the week following arterial chemo-embolization were 44.8% and 27.6%, respectively. There was a tendency for the incidence to be higher in patients treated with the anticancer agent zinostatin stimalamer (SMANCS) than in those treated with epirubicin hydrochloride (EPI). Regarding food intake, 53.1% of the patients stated that they ate "half or more than half" of the food provided on the day of arterial chemo-embolization. The rate improved as time went on. In 5 patients who experienced nausea and vomiting at the time of arterial chemo-embolization, nausea and vomiting were inhibited satisfactorily by OND. When arterial chemo-embolization was performed, antiemetic treatment for approximately 3 days was necessary to improve patients' quality of life (QOL) to an acceptable level, and OND was found to be effective for the purpose in our 5 patients who had experienced nausea and/or vomiting at the previous treatment.

[A 13-week subchronic oral toxicity study of Perilla extracts in F344 rats].

A 13-week subchronic oral toxicity study of Perilla extracts in drinking water containing 0%, 2.5%, 5% and 10% extracts was performed in both sexes of F344 rats. Rats were randomly divided into 4 groups each consisting of 10 males and 10 females. No animals died during the period of administration. There were no treatment-related changes in body weight gain or in hematological or blood biochemistry values. Nor were any treatment-related histopathological changes observed in the highest dose group. These findings indicate that ingestion of 10% Perilla extracts in drinking water for 13-week does not cause any toxicological changes in rats.

Imaging of recurrent intestinal carcinoma with indium-111-labeled anti-carcinoembryonic antigen monoclonal antibody CEA102.

CEA102 is a mouse immunoglobulin G1 monoclonal antibody (mAb) that detects an epitope of carcinoembryonic antigen (CEA). The biodistribution and imaging characteristics of indium-111-labeled (111-In)-mAb CEA102 were studied in 1 primary and 9 extrahepatic recurrent intestinal carcinoma patients. Evaluation included antibody pharmacokinetics and assessment of antibody distribution in surgical specimens, in comparison with whole body imaging using a gamma camera, and imaging with single photon emission computed tomography. Selective mAb CEA102 localization to tumor tissue was demonstrated in 7 patients with tumors over 2 cm in size, and the external images correlated well with the results of surgical inspection, pathological examination, and tissue radioactivity measurements. Tumor:serum ratios ranged from 0.20:1 to 3.22:1, and serial biodistribution study of "regions of interest" also demonstrated a high radioactivity in the tumor. These results indicated the potential exploitability of the 111-In-labeled mAb CEA102 in radioimmunodetection of primary and extrahepatic recurrence of CEA-positive intestinal carcinomas.

Transcatheter arterial embolization-induced bilious pleuritis in a patient with hepatocellular carcinoma.

A 52-year-old man with hepatocellular carcinoma (HCC) was admitted with cough and fever. He had undergone four series of treatments, including transcatheter embolization and chemoembolization with lipiodol and anticancer drugs, over the previous 2 years. Computed tomography demonstrated dilated hepatic ducts, localized necrosis in the right hepatic lobe, and subphrenic abscess. He died of respiratory failure, because of increased effusion of the right pleura, about 3 weeks after admission. Autopsy revealed adhesions in the lower lobes of the right lung, diaphragm, and liver, with granulomas with bile pigment. A fistula was observed from the necrotic regions of the right hepatic lobe to the pleura through the diaphragm. A tumor thrombus in the portal trunk was histologically confirmed as well and moderately differentiated HCC with trabecular arrangement. Direct invasion of HCC with necrotic tissue to the pleura through the diaphragm appeared to have caused the respiratory failure. Although bilious pleuritis is a rare complication of transcatheter arterial embolization (TAE), it should be considered as an adverse effect of TAE in patients with a dilated hepatic duct.

Regional adjuvant chemotherapy after partial hepatectomy for metastatic colorectal carcinoma.

The prognostic factors after hepatic resection for metastases from colorectal carcinoma were examined, and the results of adjuvant hepatic arterial chemotherapy are presented. Hepatic resection was undertaken in 57 patients with metastatic liver tumor from colorectal cancer. Adjuvant hepatic arterial chemotherapy using 5-fluorouracil, doxorubicin or epirubicin, and mitomycin C was administered to 31 patients. The 3- and 5-year survival rates for the 57 patients were 53% and 23%, respectively. The significant prognostic factors were solitary liver tumor and metachronous liver tumor. However, type of hepatectomy, surgical margin, site of the primary tumor, and histologic differentiation of the carcinoma did not relate to the prognosis. The 3- and 5-year survival rates for the patients given adjuvant arterial chemotherapy were 57% and 57%, respectively, indicating a significantly better survival rate than in the nontreated patients. These results suggest that hepatic arterial chemotherapy is effective treatment in patients with hepatic resection for metastases from colorectal carcinoma. However, recurrence in the lung is relatively high. Further improvement might be achieved by administering hepatic arterial chemotherapy as well as effective systemic chemotherapy.