胃癌におけるclaspin過剰発現の臨床病理学的意義とスフェロイド形成への関与

広島大学(Hiroshima University)博士(医学)Doctor of Philosophy in Medical Sciencedoctora

4-Hydroxy-2-Nonenal-Modified Glyceraldehyde-3-Phosphate Dehydrogenase Is Degraded by Cathepsin G in Rat Neutrophils

Degradation of oxidized or oxidatively modified proteins is an essential part of the antioxidant defenses of cells. 4-Hydroxy-2-nonenal, a major reactive aldehyde formed by lipid peroxidation, causes many types of cellular damage. It has been reported that 4-hydroxy-2-nonenal-modified proteins are degraded by the ubiquitin-proteasome pathway or, in some cases, by the lysosomal pathway. However, our previous studies using U937 cells showed that 4-hydroxy-2-nonenal-modified glyceraldehyde-3-phosphate dehydrogenase is degraded by cathepsin G. In the present study, we isolated the 4-hydroxy-2-nonenal-modified glyceraldehyde-3-phosphate dehydrogenase-degrading enzyme from rat neutrophils to an active protein fraction of 28 kDa. Using the specific antibody, the 28 kDa protein was identified as cathepsin G. Moreover, the degradation activity was inhibited by cathepsin G inhibitors. These results suggest that cathepsin G plays a crucial role in the degradation of 4-hydroxy-2-nonenal-modified glyceraldehyde-3-phosphate dehydrogenase

骨転移を有しない前立腺がん患者へのアンドロゲン除去療法による骨粗鬆症に対する経口ビスフォスフォネート製剤の予防効果について

We studied the short-term efficacy of alendronate, an oral bisphosphonates, on bone mineral density (BMD) during androgen deprivation therapy (ADT) in 45 nonmetastatic prostate cancer patients at the beginning of ADT (treatment group). All received alendronate five mg daily from the initiation of ADT. Lumber BMD was evaluated by dual energy X-ray absorptiometry, at baseline and after six months of treatment. Historical data on 24 patients with prostate cancer who received ADT without bisphosphonate administration were studied as controls (control group). BMD decreased in 13.9 and 45.8% of the patients in the treatment and control groups, respectively. Mean BMD changes in the lumber spine were +1.6 +/- 3.0% in the treatment group and -1.1 +/- 2.7% in the control group (p = 0.006). No pathological fractures occurred during the study period. No severe adverse effects were observed, but three patients could not continue alendronate treatment because of adverse events. Despite the short-term of this evaluation, our results showed that oral alendronate is an effective and safe treatment for preventing bone loss and increasing BMD in patients receiving ADT for prostate cancer.目的:アンドロゲン除去療法は骨塩減少とそれに伴う病的骨折の潜在的な危険因子である。点滴ビスフォスフォネート製剤はアンドロゲン除去療法を受けている前立腺がん患者に対する骨塩量の減少を予防することが示されているが経口ビスフォスフォネート製剤については評価されていない。今回, われわれは経口ビスフォスフォネート製剤の1つであるアレンドン酸を骨転移を有しない前立腺がん患者に投与して骨塩量を測定し短期間での効果を検討した。対象と方法:治療群として45人の骨転移を有しない前立腺がん患者について検討した。アレンドロン酸を1日5mg経口投与し治療前, 治療半年後に腰椎の骨塩量を測定し比較検討した。対照群として24人の骨転移を有しない前立腺がん患者についても同様に検討を行った。結果:骨塩量の減少は治療群で13.9%, 対照群で45.8%に見られた。腰椎における骨塩量の変化は治療群で平均1.6%, 対照群で-1.1%であった(p=0.006)。治療期間内において病的骨折は認められず, 有害事象として重篤なものは認めなかったが副作用のため3例が内服継続困難であった。結語:短期間の検討であるにもかかわらず経口ビスフォスフォネート製剤であるアレンドロン酸は前立腺がん患者に対するアンドロゲン除去療法による骨塩量減少を予防するのに有効で安全な治療法であることが示唆された。(著者抄録

12(S)-Hydroxyeicosatetraenoic acid induces cAMP production via increasing intracellular calcium concentration

AbstractWe have found that a 12-lipoxygenase metabolite of arachidonic acid, 12(S)-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-HETE), induces cAMP production in human normal fibroblast TIG-1 cells. This phenomenon was not observed in other cells tested including human embryonic kidney HEK293 cells. We have speculated that this specific response might be influenced by the kinds of isoform of adenylyl cyclase (AC) present in cells. We found that TIG-1 cells specifically expressed type VIII AC. As type VIII AC is known to be activated by an increase of calcium concentration, we determined the change of intracellular Ca2+ concentration after the addition of 12-HETE. It was elevated not only in TIG-1 cells, but also HEK293 cells, which did not respond to 12-HETE to produce cAMP. The addition of a calcium ionophore elevated the concentration of intracellular cAMP in TIG-1 cells, but it was without effect in HEK293 cells. To show that the expression of this particular isoform of AC is responsible for the positive response to 12-HETE, we transfected this AC isoform into HEK293 cells. The type VIII AC-transfected cells, in contrast to the mock-transfected ones, became very responsive to 12-HETE to produce cAMP. Taken all together the data would strongly suggest that 12-HETE specifically activates type VIII AC via increasing intracellular Ca2+ concentration

Endosonography-Guided Pancreatic Duct Drainage for Chronic Pancreatitis: A Case Report and Review

A 50-year-old man was admitted to our department, complaining of epigastric pain and high fever. CT revealed a pseudocyst at the pancreatic head with upstream dilatation of the pancreatic duct (PD) and fluid collection surrounding the pancreas. Endosonography-guided PD drainage (ESPD) was performed because of unsuccessful ERCP. With a curved linear array echoendoscope, a 7.2 F catheter was placed in the PD. Laboratory data showed improvement in a few days and revealed disappearance of the fluid collection. Ten days after ESPD, a 7 F stent was placed in the PD via the puncture tract across the papilla of Vater followed by transpapillary replacement with a 10 F stent. CT showed a reduction in diameter of the PD and disappearance of the pseudocyst. ESPD is a feasible and useful procedure in selected patients with chronic pancreatitis showing stenosis of the main PD when transpapillary approach is impossible

ANTITUMOUR EFFECT OF VALPROIC ACID AGAINST SALIVARY GLAND CANCER

Salivary gland cancer (SGC) has a comparatively poor prognosis and is prone to frequent recurrence and metastases. Therefore, the development of more effective chemotherapy against SGC is desirable. The aim of the present study was to investigate the antitumour effects of valproic acid (VPA) against SGC in vitro and in vivo. Two human SGC cell lines (HSY and HSG cells) were used in the present study. The effects of VPA on the proliferation of SGC cells in vitro were assessed by MTT assay. Cancer cells treated with VPA were subjected to cell cycle analysis by flow cytometry. In addition, the expression levels of p21 and p27 were examined by real-time RT-PCR to identify the mechanisms of the antitumour effect of VPA on SGC. The effects of VPA on cancer growth in vivo were evaluated in a xenograft model. VPA inhibited the proliferation of SGC cells in a dose-dependent manner in vitro. Degenerated cancer cells were observed at high concentrations of VPA. In the cell cycle analysis, VPA induced cell-growth inhibition and G1 arrest of cell cycle progression in both cancer cell lines in a time-and dose-dependent manner. VPA markedly upregulated the mRNA expression levels of both p21 and p27 in both SGC cell lines in a time-dependent manner. In the xenograft model experiment, VPA treatment markedly inhibited the growth of salivary gland tumours when compared with the growth of the untreated controls. VPA may be a valuable drug in the development of better therapeutic regimens for SGC

Newly Developed Fully Covered Metal Stent for Unresectable Malignant Biliary Stricture

We herein report two patients with unresectable malignant biliary stricture who underwent stenting with a newly developed fully-covered metal stent. In the first case of lower-middle bile duct cancer, a stent was placed through the stenosis. In the second case of middle bile duct stricture due to lymph node metastases from gallbladder cancer, a stent was placed in the bile duct across the stenosis. No procedure-related complications were observed. Unevenness of the outer surface and a low shortening ratio are expected to lessen the occurrence of complications characteristic of covered metal stents such as stent migration and bile duct kinking

Molecular and geographic analyses of vampire bat-transmitted cattle rabies in central Brazil

<p>Abstract</p> <p>Background</p> <p>Vampire bats are important rabies virus vectors, causing critical problems in both the livestock industry and public health sector in Latin America. In order to assess the epidemiological characteristics of vampire bat-transmitted rabies, the authors conducted phylogenetic and geographical analyses using sequence data of a large number of cattle rabies isolates collected from a wide geographical area in Brazil.</p> <p>Methods</p> <p>Partial nucleoprotein genes of rabies viruses isolated from 666 cattle and 18 vampire bats between 1987 and 2006 were sequenced and used for phylogenetic analysis. The genetic variants were plotted on topographical maps of Brazil.</p> <p>Results</p> <p>In this study, 593 samples consisting of 24 genetic variants were analyzed. Regional localization of variants was observed, with the distribution of several variants found to be delimited by mountain ranges which served as geographic boundaries. The geographical distributions of vampire-bat and cattle isolates that were classified as the identical phylogenetic group were found to overlap with high certainty. Most of the samples analyzed in this study were isolated from adjacent areas linked by rivers.</p> <p>Conclusion</p> <p>This study revealed the existence of several dozen regional variants associated with vampire bats in Brazil, with the distribution patterns of these variants found to be affected by mountain ranges and rivers. These results suggest that epidemiological characteristics of vampire bat-related rabies appear to be associated with the topographical and geographical characteristics of areas where cattle are maintained, and the factors affecting vampire bat ecology.</p

Relationship between silent brain infarction and chronic kidney disease

Background. The presence of silent brain infarction (SBI) increases the risk of symptomatic stroke and dementia. The association between SBI and chronic kidney disease (CKD) has not been clarified. Moreover, little is known about what factors are related to SBI in CKD patients and whether the prevalence of SBI differs in CKD stage or cause of CKD