Immunohistochemical analysis of Fas and FLIP in prostate cancers

Fas‐mediated apoptosis is considered a principal pathway for apoptosis induction in normal and cancer cells. Expression of Fas has been reported in prostate tissues several times, but the data were not consistent. Expression of FLICE‐like inhibitory protein (FLIP), an inhibitor of Fas‐mediated apoptosis, has not been studied by immunohistochemistry in prostate tissues. The aim of this study is to explore whether alterations of Fas and FLIP expression occur in prostate cancer tissues. We analyzed the expression of Fas and FLIP in 107 prostate adenocarcinoma tissues by immunohistochemistry using a tissue microarray approach. Normal glandular cells of the prostates strongly expressed both Fas and FLIP proteins. Prostate intraepithelial neoplasm also showed a strong Fas immunoreacitity. Fas expression was strongly positive in 60 cancers (56.1%), but the remaining 47 cancers showed no (6.5%) or markedly decreased (37.4%) Fas immunostaining compared with the normal glandular cells of the same patients. By contrast, FLIP expression was strong in most (103/107; 96.3%) of the cancers, and only four cancers (3.7%) showed decreased immunoreactivities compared with the normal cells. The decreased expression of Fas was not associated with pathologic characteristics, including FLIP expression, size of the cancers, age, Gleason score and stage. The decreased expression of Fas in a large fraction of prostate cancers compared with their normal cells suggested that loss of Fas expression might play a role in tumorigenesis in some prostate cancers possibly by inhibiting apoptosis mediated by Fas.     

Signal transduction pathway in human middle ear cholesteatoma

Phospholipase C-gamma1 plays a central role in signal transduction, and it is important in cellular growth, differentiation, and proliferation. Human cholesteatoma in the middle ear is characterized by the presence of a keratinizing epithelium that is believed to have hyperproliferative properties. The purpose of this study is to elucidate the distribution of phospholipase C-gamma1 in cholesteatoma matrix and deep meatal skin with Western blot analysis and immunohistochemistry. In conclusion, overexpression of phospholipase C-gamma1 in cholesteatoma matrix suggests a possible derangement of enhanced growth signal transduction in keratinocytes.     

Morphogenesis and Regulation of Bergmann Glial Processes During Purkinje Cell Dendritic Spine Ensheathment and Synaptogenesis

星形胶质细胞在突触形成中发挥重要作用,但星形胶质细胞突起如何在发育过程中与突触结构相联系还不是很清楚。本文分析在小脑突触发生过程中Bergmann胶质细胞(BG)突起生长的类型。本文发现在这个过程中,BG突起向外生长与树突棘增多的包被作用相关。此外,双光子时间分辩显像显示BG突起是高度动态的,在棘包被过程中突起趋于稳定。虽然突触活力依赖于肌动蛋白的聚合作用,但细胞骨架调节器Rac1和RhoG的活动在胶质细胞突起的动力或密度上并未发挥作用,而是对于保持突起长度起关键性作用。本文扩展这个发现,探查突起形态和包被之间的关系,发现缩短的突起导致棘覆盖的减少。本文进一步发现在BG表达dn-Rac1和低水平突触包被的区域,显示突触数量的增加。这些分析提示BG突起如何生长并包围突触结构,阐明BG突起结构对突触包被适当发育的重要性,并提示包被在突触形成中的作用。     

Inadvertent Detection of 60-Hz Alternating Current by an Implantable Cardioverter Defibrillator

LEE, S.W., et al. : Inadvertent Detection of 60-Hz Alternating Current by an Implantable Cardioverter De-fibrillator. A patient with an ICD received therapies from his ICD while exercising in an indoor swimming pool. Interrogation of the ICD revealed inappropriate detection of 60-Hz alternating current artifact and delivery of ICD therapies.     

Isoflurane attenuates dynorphin-induced cytotoxicity and downregulation of Bcl-2 expression in differentiated neuroblastoma SH-SY5Y cells

Background: It has been proposed that the volatile anesthetic isoflurane induces neuroprotection and that the endogenous opioid peptide dynorphin induces neurocytotoxicity in cells. The levels of dynorphin are often significantly elevated in neuropathophysiological conditions, and dynorphin can directly induce toxicity. However, the neuroprotective effects of isoflurane on dynorphin-induced cytotoxicity are still unclear.
Methods: In order to determine the effect of isoflurane on dynorphin-induced cytotoxicity in neuronal cells, we have designed a device wherein cultured human neuroblastoma SH-SY5Y cells can be exposed to isoflurane. Fully differentiated SH-SY5Y cells were obtained by treating the cells with retinoic acid for 6 days. We examined SH-SY5Y cell survival, apoptosis, and antiapoptotic protein expression by cell viability, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling stain, and Western blot analysis, respectively.
Results: After 16 h of dynorphin (10 μM) treatment, the SH-SY5Y cells showed significant cytotoxicity, apoptosis, and downregulation of the antiapoptotic Bcl-2 protein expression. These effects of dynorphin were significantly inhibited by isoflurane exposure for 32 h [pretreatment for 16 h and posttreatment (after dynorphin treatment) for 16 h].
Conclusion: Thus, our results suggest that isoflurane exerts neuroprotective effects in the case of dynorphin-induced pathophysiological disruption.     

Predictors of corticosteroid-dependent and corticosteroid-refractory inflammatory bowel disease: analysis of a Chinese cohort study

Background  Patients with inflammatory bowel disease (IBD) who are corticosteroid-dependent or -refractory are at higher risk of developing disease- and treatment-related complications.
Aims  To identify retrospectively clinical factors present at diagnosis that predict the occurrence of corticosteroid dependency and refractoriness in Crohn's disease (CD) and ulcerative colitis (UC) patients.
Methods  A total of 310 IBD patients (134 CD, 176 UC) were observed for 2140 person years and their use of systemic corticosteroids was determined. Outcomes of corticosteroid dependency and refractoriness were recorded. Univariate and multivariate analyses were performed to determine the clinical factors associated with outcomes.
Results  Seventy-seven (57.5%) CD and 95 (54.0%) UC patients had received corticosteroids during study period. In CD, thrombocytosis [Hazard ratio (HR):3.0] predicted, whereas colonic CD (HR:0.3) negatively predicted corticosteroid dependency. Stricturing phenotype (HR:4.5) predicted corticosteroid-refractory CD. For UC, thrombocytosis (HR:3.9) and extensive colitis (HR:1.7) predicted corticosteroid dependency. Presence of anaemia (HR:10.8) at diagnosis and initial requirement of total parenteral nutrition (TPN) (HR:18.8) predicted corticosteroid-refractory UC. The cumulative risks of surgery were 17.8% and 5.4% for CD and UC patients respectively at 1 year after starting corticosteroids.
Conclusions  Thrombocytosis at diagnosis predicted corticosteroid-dependency in IBD. Stricturing phenotype of CD and the presence of anaemia in UC predicted subsequent course of corticosteroid refractoriness.     

Bacterial biofilm formation on nasogastric tubes

We examined the external surfaces of the gastric portion of nasogastric tubes recovered from hospitalized patients. Most of these surfaces were covered with a thick amorphous biofilm which was shown to be largely composed of microbial microcolonies in which individual cells were enclosed in their exopolysaccharide glycocalyces. Bacteria of many different morphotypes and some yeast cells were found in a fibrillar matrix that appeared to mediate their attachment to the silastic tubing. Within these mature biofilms some microcolonies were structurally intact and apparently vigorous, while others were composed largely of dead cells and empty cell walls. We conclude that nasogastric tubes that remain in patients for as short a time as one day are heavily colonized by a rich variety of biofilm-forming bacteria and yeasts.     

HCV and HBV coexist in HBsAg-negative patients with HCV viraemia: Possibility of coinfection in these patients must be considered in HBV-high endemic area

Hepatocellular carcinoma (HCC) is one of the most common cancers and is highly associated with hepatitis B virus (HBV) infection in Korea. The role of HBV and hepatitis C virus (HCV) in HCC patients who are negative for hepatitis B surface antigens (HBsAg) remains poorly defined. It has been suggested that HCV core protein may impair the polymerase activity of HBV in vitro, potentially lowering HBV titre in coinfected patients. Therefore, routine enzyme immunoassay may not detect HBV, in spite of the presence of HBV viraemia in low titres. The aim of this study was to confirm the coexistence of HBV viraemia in hepatitis C-infected patients with HCC who have apparent HBsAg seronegativity and to establish the need for clinical reinterpretation of enzyme immunoassay (EIA) serological tests of HBsAg in patients with HCV viraemia and HCC. The serological profiles of HBV and HCV in 616 patients with HCC were analysed and the coinfection rate of HCV and HBV investigated. Sera were obtained from 16 patients who were both anti-HCV and HCV-RNA positive but HBsAg negative, and tested for HBV by polymerase chain reaction (PCR). Eleven non-A and non-B chronic hepatitis patients without HCC who had the same profiles of anti-HCV, HCV-RNA, and HBsAg were tested for HBV by PCR. As a control group, sera were obtained from 15 patients with HCC and 30 non-A and non-B chronic hepatitis patients without HCC; both were anti-HCV, HCV-RNA, and HBsAg negative and tested for HBV PCR. Of the 616 patients with HCC, 450 (73.1%) had current HBV infection, 48 (7.8%) had anti-HCV antibodies, and nine (1.5%) had viral markers of both HCV and HBV by serological profiles. Of the 27 patients with HCV viraemia and HBsAg seronegativity (16 with HCC; 11 with non-A non-B chronic hepatitis), 14 (51.9%) showed HBV viraemia by PCR. In contrast, of the 75 patients in the control group (45 with HCC; 30 with non-A and non-B chronic hepatitis) who were both HCV PCR negative and HBsAg negative, five (11.1%) showed HBV viraemia by PCR. The PCR for HBV revealed coexistent HBV viraemia in HCV viraemia patients, despite HBsAg negativity by EIA. In HBV-endemic areas, the possibility of coinfection of HBV in HBsAg-negative patients with HCV viraemia should be considered and molecular analysis for HBV-DNA performed.     

Polymorphous Ventricular Tachycardia Associated with a Marked Prolongation of the Q-T Interval Induced by Amiodarone

We report the case of a patient who developed a life-threatening polymorphous ventricular tachycardia (PVT) after six weeks of treatment with amiodarone. The Q-T interval was markedly prolonged at 0.86 second. The drug induction of PVT was strongly suggested by the fact that PVT resolved four days after withdrawal of amiodarone when the Q-T interval had shortened to 0.60 second; the arrhythmia has not recurred in the nine months of follow-up since then. Amiodarone, though a very effective antiarrhythmic agent, may induce serious PVT.