Design and synthesis of biotin- or alkyne-conjugated photoaffinity probes for studying the target molecules of PD 404182.

To investigate the mechanism of action of the potent antiviral compound PD 404182, three novel photoaffinity probes equipped with a biotin or alkyne indicator were designed and synthesized based on previous structure-activity relationship studies. These probes retained the potent anti-HIV activity of the original pyrimidobenzothiazine derivatives. In photoaffinity labeling studies using HIV-1-infected H9 cells (H9IIIB), eight potential proteins were observed to bind PD 404182

Surgery for Perforating Intestial Behcet\u27s Disease

We reported the surgical experience with perforating intestinal Behcet\u27s diesease in a 36-year-old male and discussed mainly the operation method to avoid recurrence and postoperative complications

Laparoscopic total colectomy with lymph node dissection for familial adenomatous polyposis with multiple colorectal cancers

　A 49-year-old Japanese man visited our hospital with chief complaints of difficulty with and bleeding during defecation. After a detailed examination, he was diagnosed with familial adenomatous polyposis (FAP) with multiple (five) colorectal cancers. The tumors were located in the right-sided, left-sided, and sigmoid colon, and the lower rectum. Regional lymph node involvement was observed, but no metastasis to other organs was detected. We, therefore, performed a laparoscopic total colectomy with superior mesenteric artery (SMA) and inferior mesenteric artery (IMA) lymph node dissection. We were able to perform minimally invasive and cosmetically acceptable surgery using laparoscopy instead of highly-invasive open abdominal surgery. Our search of the literature revealed no reported cases of laparoscopic total colectomy with lymph node dissection for FAP with multiple colorectal cancers, making the present case the first to be reported in the literature

Hepatitis B virus X protein overcomes oncogenic RAS-induced senescence in human immortalized cells

医薬保健研究域医学系Chronic infection with hepatitis B virus (HBV) is a major risk factor for hepatocellular carcinoma. The HBV X protein (HBx) is thought to have oncogenic potential, although the molecular mechanism remains obscure. Pathological roles of HBx in the carcinogenic process have been examined using rodent systems and no report is available on the oncogenic roles of HBx in human cells in vitro. We therefore examined the effect of HBx on immortalization and transformation in human primary cells. We found that HBx could overcome active RAS-induced senescence in human immortalized cells and that these cells could form colonies in soft agar and tumors in nude mice. HBx alone, however, could contribute to neither immortalization nor transformation of these cells. In a population doubling analysis, an N-terminal truncated mutant of HBx, HBx-D1 (amino acids 51-154), which harbors the coactivation domain, could overcome active RAS-induced cellular senescence, but these cells failed to exhibit colonigenic and tumorigenic abilities, probably due to the low expression level of the protein. By scanning a HBx expression library of the clustered-alanine substitution mutants, the N-terminal domain was found to be critical for overcoming active RAS-induced senescence by stabilizing full-length HBx. These results strongly suggest that HBx can contribute to carcinogenesis by overcoming active oncogene-induced senescence. © 2007 Japanese Cancer Association

Aesthetic pectoral muscle flap repair for refractory enterocutaneous fistula after salvage esophagectomy in a female patient

Anastomotic leakage is a severe complication of esophagectomy. Development of an enterocutaneous fistula after anastomotic leakage often occurs after subcutaneous-route reconstruction at esophagectomy. Pectoralis myocutaneous flap (PMCF) repair has recently been performed when an enterocutaneous fistula was refractory to conservative treatment. However, this procedure requires a conspicuous incision and results in deformity of the breast especially in female patient. We performed pectoralis muscle flap (PMF) repair for a 50-year-old woman with a refractory enterocutaneous fistula after salvage esophagectomy. We made an oblique incision along the inframammary crease in order to avoid a conspicuous scar and moved the PMF under the mammary gland to the site of anastomosis. This method was effective for repairing a refractory enterocutaneous fistula, with especially good aesthetic results in a female patient

Bioorganic synthesis of a recombinant HIV-1 fusion inhibitor, SC35EK, with an N-terminal pyroglutamate capping group.

The bioorganic synthesis of an end-capped anti-HIV peptide from a recombinant protein was investigated. Cyanogen bromide-mediated cleavage of two Met-Gln sites across the target anti-HIV sequence generated an HIV-1 fusion inhibitor (SC35EK) analog bearing an N-terminal pyroglutamate (pGlu) residue and a C-terminal homoserine lactone (Hsl) residue. The end-capped peptide, pGlu-SC35EK-Hsl, had similar bioactivity and biophysical properties to the parent peptide, and an improved resistance to peptidase-mediated degradation was observed compared with the non-end-capped peptide obtained using standard recombinant technology

The effects of once-weekly teriparatide on hip structure and biomechanical properties assessed by CT

Once-weekly administration of 56.5 μg teriparatide improved cortical bone parameters and biomechanical parameters at the proximal femur by CT geometry analysis. Introduction: The aim of this study was to evaluate the effects of weekly administration of teriparatide [human PTH (1-34)] on bone geometry, volumetric bone mineral density (vBMD), and parameters of bone strength at the proximal femur which were longitudinally investigated using computed tomography (CT). Methods: The subjects were a subgroup of a recent, randomly assigned, double-blind study (578 subjects) comparing the anti-fracture efficacy of a once-weekly subcutaneous injection of 56.5 μg teriparatide with placebo (TOWER trial). Results: Sixty-six ambulatory postmenopausal women with osteoporosis were enrolled at 15 study sites having multi-detector row CT, and included women injected with teriparatide (n = 29, 74.2 ± 5.1 years) or with placebo (n = 37, 74.8 ± 5.3 years). CT data were obtained at baseline and follow-up scans were performed at 48 and 72 weeks. The data were analyzed to obtain cross-sectional densitometric, geometric, and biomechanical parameters including the section modulus (SM) and buckling ratio (BR) of the femoral neck, inter-trochanter, and femoral shaft. We found that once-weekly teriparatide increased cortical thickness/cross-sectional area (CSA) and total area, and improved biomechanical properties (i.e., decreasing BR) at the femoral neck and shaft. Teriparatide did not change the cortical perimeter. Conclusions: Our longitudinal analysis of proximal femur geometry by CT revealed that once-weekly administration of 56.5 μg teriparatide improved cortical bone parameters at the femoral neck and shaft and also improved biomechanical parameters

A case of asymptomatic right-sided adult Bochdalek hernia presented incidentally with rectal tumor

　We encountered a patient with an adult Bochdalek hernia discovered asymptomatically. A 77-year-old Japanese woman visited a local clinic with chief complaints of melena and difficulty in defecation. Based on the results of the detailed examination in our hospital, she was diagnosed with a rectal gastrointestinal stromal tumor (GIST) with a concurrent asymptomatic adult right-sided Bochdalek hernia. Because the tumor was large, laparoscopic abdominoperineal rectal amputation was performed after systemic imatinib therapy. During the surgery, we found a right diaphragmatic defect more than 13cm in long dia., through which the right hepatic lobe, colon, and greater omentum had prolapsed into the right thoracic cavity. No visceral adhesions were noted. No hernia sac was observed. Adult Bochdalek hernia is a relatively rare condition, and only three (incidentally discovered) cases of asymptomatic Bochdalek hernia, including the present case, have been reported in Japan. Here we provide a case report for the patient, who was followed-up without hernia surgery, plus a review of the literature

A case of laparoscopic and endoscopic cooperative surgery for sigmoidovesical fistula

We performed laparoscopic and endoscopic cooperative surgery (LECS) for partial colectomy with partial cystectomy in an 80-year-old woman with sigmoidovesical fistula secondary to sigmoid diverticulitis. LECS was designed for local resection of the stomach for gastric submucosal tumors using the endoscopic submucosal dissection (ESD) technique. While conventional open abdominal surgery is very invasive, LECS has enabled surgeons to perform minimally invasive surgery. Although there have been no reported cases in which the bladder was laparoscopically resected after sigmoidovesical fistula division, we were able to safely resect the fistula and preserve the urethral opening by performing laparoscopic and cystoscopic cooperative surgery. There are no previously reported cases in which LECS was performed for partial sigmoidectomy and partial cystectomy ; therefore, we report this as a valuable case, with a review of the literature. We hope that further studies involving more patients will lead to the establishment of this procedure

Identification of minimal sequence for HIV-1 fusion inhibitors.

Emergence of multi-drug resistant HIV-1 is a serious problem for AIDS treatment. Recently, the virus-cell membrane fusion process has been identified as a promising target for the development of novel drugs against these resistant variants. In this study, we identified a 29-residue peptide fusion inhibitor, SC29EK, which shows activity comparable to the previously reported inhibitor SC35EK. Some residues in SC29EK not required for interaction with virus gp41 heptad repeat 1 (HR1) were replaced with a non-proteinogenic amino acid, 2-aminoisobutyric acid (Aib), to stabilize the alpha-helix structure and to provide resistance to peptidases