1，25－双羟维生素D_3对培养人角朊细胞增殖，细胞形态及HLA－DR，ICAM－1表达的影响

用体外培养人角朊细胞研究了１．２５－双羟维生素Ｄ_３（１，２５（ＯＨ）_２Ｄ_３）对角朊细胞增殖，细胞形态及ＨＬＡ－ＤＲ，ＩＣＡＭ－１分子表达的影响，培养液中加入１，２５（ＯＨ）_２Ｄ_３可使细胞增殖明显抑制。用流式细胞仪测定，１，２５（ＯＨ）_２Ｄ_３处理６天后角朊细胞体积较未处理的明显变大。用免疫组化染色显示１，２５（ＯＨ）_２Ｄ_３对经ＩＦＮ－γ和ＴＮＦａ刺激的角朊细胞ＨＬＡ－ＤＲ和ＩＣＡＭ－１分子表达无明显影响。     

Effective segmental chemoembolization of advanced hepatocellular carcinoma with tumor thrombus in the portal vein

Purpose: Evaluate therapeutic results of transcatheter segmental hepatic artery chemo-oily-embolization (segmental TAE) against advanced hepatocellular carcinomas (HCC) accompanied by portal tumor thrombus (PTT). Methods: Segmental TAE was performed in nine patients with hepatic cirrhosis and advanced HCCs accompanied by PTT. Four subsegmental portal branches were obstructed by PTT in three patients, and two were obstructed in the remaining six patients. TAE was performed into the targeted segmental hepatic artery followed by embolization with gelatin sponge particles. Results: In one patient undergoing subsequent resection, a marked anticancer effect on the PTT was demonstrated histologically. In the eight other patients who did not undergo subsequent resection, the cumulative survival rates were 67% at 6 months, 44% at 1 year, and 22% at 2 years. No serious complications were noted. Conclusions: This therapeutic approach is thought to be a useful treatment for HCC with PTT, because it reinforces anticancer effects and can be performed more safely than conventional transcatheter arterial embolization.     

Treatment of a patient with hemophilia A and hepatitis C virus-related cirrhosis by living-related liver transplantation from an obligate carrier donor

BACKGROUND: Decompensated hepatitis C virus (HCV)-related cirrhosis is the main indication for liver transplantation. We report the first successful living-related liver transplantation in a 49-year-old hemophilia A patient with end-stage HCV-related cirrhosis using a graft obtained from his 20-year-old daughter, an obligate carrier. METHODS: The donor's autologous fresh-frozen plasma rich in factor VIII (FVIII) by treatment with 1-deamino-8-D-arginine vasopressin was prepared before the operation. At induction, 1-deamino-8-D-arginine vasopressin was given to the donor to increase plasma FVIII level. In addition, autologous fresh-frozen plasma containing high FVIII concentrate was infused intraoperatively. The right lobe was harvested from the donor and transplanted orthotopically. The recipient was treated postoperatively with recombinant FVIII and immunosuppressive agents. RESULTS: The donor did not receive recombinant FVIII or allogenic blood during perioperative periods. No bleeding was encountered in the donor perioperatively. The recipient showed a steady increase in FVIII activity postoperatively and was discharged 40 days after transplantation. Ribavirin and interferon-alpha were provided for 3 months postoperatively to prevent potential recurrence of HCV infection. Serum HCV-RNA by RT-PCR became negative after such treatment. CONCLUSIONS: End-stage liver disease in patients with hemophilia A can be an indication for living-related liver transplantation. Furthermore, a graft from a living-related donor with hemophilia A carrier seems to be suitable provided such individuals receive adequate support for coagulopathies.     

Expression profiling of Ca2+/calmodulin-dependent signaling molecules in the rat dorsal and ventral hippocampus after acute lead exposure

The septal and temporal poles of the hippocampus differ markedly in their anatomical organization, but whether these distinct regions exhibit differential neurochemical profiles underlying lead (Pb²⁺) neurotoxicity remains to be determined. In the present study, we examined changes in the expression of Ca²⁺/calmodulin-dependent enzymes, including calpain, calcineurin, phospho-CaMKII (Thr286) and neuronal nitric oxide synthase (nNOS), in the rat dorsal and ventral hippocampus (DH and VH) after acute Pb²⁺ exposure. Five days after Pb²⁺ exposure, we observed constitutively active forms of calcineurin (45 kDa and 48 kDa) in ventral portions of the hippocampus, a result consistent with the observed calpain activation that is indicated by the breakdown of spectrin in this region. Our data demonstrate that nNOS expression is significantly higher in the ventral region of the hippocampus when compared to the dorsal region, whereas phosphorylation of CaMKII (Thr286) is less pronounced in the ventral portion of the hippocampus and more pronounced in dorsal regions after acute Pb²⁺ exposure. Thus, it appears likely that the ventral region of hippocampus is more vulnerable to the neurotoxic effects of Pb²⁺ than the dorsal region. Taken together, the present data suggest that acute lead exposure leads to differential expression patterns of Ca²⁺/calmodulin-dependent enzymes along the dorsoventral axis of the hippocampus.     

Effects of metformin administration on plasma gonadotropin levels in women with infertility,with an in vitro study of the direct effects on the pituitary gonadotrophs

Changes in LH and FSH levels were evaluated before and after metformin administration. In all 25 patients, plasma LH levels were significantly reduced after 3 months of metformin administration (500–1,500 mg/day). When patients were classified into a PCOS group (n = 12) or a non-PCOS group (n = 13), the reduction in LH levels only remained significant in the PCOS group. Plasma FSH levels were unchanged following metformin treatment when all patients were considered collectively and when patients were classified based on PCOS. LH/FSH ratio was significantly reduced only in the PCOS group. To examine the direct effect of metformin on gonadotropin-secreting cells, gonadotroph cell line, LβT2 was used for in vitro studies. Treatment of LβT2 cells with metformin modified neither the LHβ nor the FSHβ subunit promoter activity. The GnRH-induced LHβ promoter activity was not modulated in the presence of metformin. In contrast, GnRH-induced FSHβ promoter activity was significantly potentiated in the presence of metformin. Our results suggest that metformin does indeed modulate the basal level of LH and the LH/FSH ratio, albeit indirectly, particularly in the patients with PCOS. Additionally our results suggest that metformin does directly regulate FSH gene expression.     

Expression of the bric-a-brac tramtrack broad complex protein NAC-1 in cervical carcinomas seems to correlate with poorer prognosis.

PURPOSE: Recent studies have suggested a novel oncogenic role of a bric-a-brac tramtrack broad complex (also known as POZ) domain gene, NAC-1, in ovarian carcinomas. The aim of this study was to clarify the functional role of NAC-1 in human cervical carcinomas. EXPERIMENTAL DESIGN: NAC-1 expression in cervical cancer was assessed by immunohistochemistry, and data on clinical variables were collected by retrospective chart review. NAC-1 gene knockdown using small interfering RNA and a NAC-1 gene transfection system were used to asses NAC-1 function in cervical cancer in vivo. RESULTS: Immunohistochemical and gene expression analysis revealed that NAC-1 is significantly overexpressed in cervical adenocarcinomas and adenosquamous carcinomas compared with squamous cell carcinomas. Patients with squamous cell carcinomas positive for NAC-1 expression who received radiotherapy had significantly shorter overall survival than peers whose tumors did not express NAC-1, and multivariate analysis showed that NAC-1 expression was an independent prognostic factor for overall survival after radiotherapy. Overexpressions of the NAC-1 gene stimulated cell proliferation in cervical carcinoma cells of the TCS, CaSki, and HeLa P3 lines, which do not have endogenous NAC-1 expression. NAC-1 gene knockdown inhibited cell growth and induced apoptosis in HeLa, HeLa TG, and ME180 cells, all of which overexpressed NAC-1. CONCLUSIONS: Our findings suggest that NAC-1 may play an important role in cervical carcinomas; moreover, these findings provide a rationale for future development of NAC-1-based therapy for cervical carcinomas that overexpress this candidate oncogene.