Calcium calmodulin dependent kinase kinase 2 - a novel therapeutic target for gastric adenocarcinoma

Gastric cancer is one of the most common gastrointestinal malignancies and is associated with poor prognosis. Exploring alterations in the proteomic landscape of gastric cancer is likely to provide potential biomarkers for early detection and molecules for targeted therapeutic intervention. Using iTRAQ-based quantitative proteomic analysis, we identified 22 proteins that were overexpressed and 17 proteins that were downregulated in gastric tumor tissues as compared to the adjacent normal tissue. Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) was found to be 7-fold overexpressed in gastric tumor tissues. Immunohistochemical labeling of tumor tissue microarrays for validation of CAMKK2 overexpression revealed that it was indeed overexpressed in 94% (92 of 98) of gastric cancer cases. Silencing of CAMKK2 using siRNA significantly reduced cell proliferation, colony formation and invasion of gastric cancer cells. Our results demonstrate that CAMKK2 signals in gastric cancer through AMPK activation and suggest that CAMKK2 could be a novel therapeutic target in gastric cancer.     

Pandemic influenza vaccination elicits influenza-specific CD4+ Th1-cell responses in hypogammaglobulinaemic patients: four case reports

In these case reports, we investigated pandemic influenza 2009 vaccination of primary hypogammaglobulinaemic patients. Three combined variable immunodeficiency (CVID) patients and one X-linked agammaglobulinaemia (XLA) patient were vaccinated with the pandemic vaccine A/California/7/2009 (H1N1)-like split virus (X179a) adjuvanted with the oil-in-water emulsion AS03. Subsequently, serum and peripheral blood mononuclear cells were sampled and used to measure the haemagglutination inhibition (HI) and antibody-secreting cell (ASC) responses. In addition, the IFN-γ, IL-2 and TNF-α producing CD4(+) Th1-cell response was determined as these cytokines are important indicators of cell-mediated immunity. Two of the CVID patients responded to vaccination as determined by a >4-fold rise in HI antibodies. These subjects also had influenza-specific ASC numbers, which, albeit low, were higher than prevaccination levels. In addition, vaccination induced CD4(+) Th1-cell responses in both the XLA patient and the CVID patients, although the frequency of influenza-responsive cells varied amongst the patients. These results suggest that hypogammaglobulinaemia patients can mount a CD4(+) Th1 cell-mediated response to influenza vaccination and, additionally, that influenza vaccination of some hypogammaglobulinaemia patients can produce an influenza-specific humoral immune response. The findings should be confirmed in larger clinical studies.     

一氧化氮在神经退行性疾病中的作用:非类固醇性抗炎药的治疗前景(英文)

一氧化氮(nitric oxide, NO)是一类胞内信使。研究表明,神经退行性病人脑组织中催化合成NO的酶的表达水平显著提高,提示NO与神经退行性疾病密切相关。此外,在这些组织中还检测到硝化的蛋白,提示NO在这些组织中具有生物活性。在神经免疫应答中,神经元和胶质细胞(包括小胶质细胞和星形胶质细胞)内都发生了NO水平的改变。很多神经退行性疾病都伴随有神经炎症,抑制神经炎症的信号通路能延迟这些疾病的发展。因此,NO及其释放通路已逐渐成为神经退行性疾病研究领域的热点,对它们的理解能帮助我们找到合适的方案来预防、减缓或者治愈这些疾病。     

Caecal perforation with faecal peritonitis – unusual presentation of Bochdalek hernia in an adult: a case report and review of literature

The improper fusion of the postero-lateral foramen of the diaphragm was first described by Bochdalek in 1848. The incidence of congenital diaphragmatic hernia varies from1:2000 to 1:5000 live births and Bochdalek hernias (BH) account for 75 to 85% of these. Although it is a well-known entity in neonates, it is occasionally discovered incidentally in adult patients. Until now, a total of around 100 cases of occult asymptomatic Bochdalek hernia have been reported. The symptomatic cases are encountered more rarely. Colon necrosis among the symptomatic cases was reported in some reports. We discuss the present case since we believe it to be, to the best of our knowledge, the first case of a Bochdalek hernia in an adult presenting with caecal perforation and faecal peritonitis and review the published literature about this rare condition.     

Arab nations lagging behind other Middle Eastern countries in biomedical research: a comparative study

Background  

Analysis of biomedical research and publications in a country or group of countries is used to monitor research progress and trends. This study aims to assess the performance of biomedical research in the Arab world during 2001–2005 and to compare it with other Middle Eastern non-Arab countries.     

High-resolution analysis of von Willebrand factor multimeric composition defines a new variant of type I von Willebrand disease with aberrant structure but presence of all size multimers (type IC)

In Type I von Willebrand disease, the whole series of von Willebrand factor (vWF) multimers is present in plasma, but all are decreased in quantity. No structural abnormality of individual multimers has been demonstrated so far in these patients. We now describe five individuals, from two unrelated families, who had this form of the disease and in whom the complex banding pattern of each vWF multimer was markedly abnormal. Inheritance was autosomal dominant and the clinical expression was mild. A bleeding history was elicited in three of the patients and included recurrent epistaxis, menometrorrhagia, and bleeding following tooth extraction. Replacement therapy had never been required. Although vWF levels in plasma were within the normal range in all of them, the ristocetin cofactor activity was decreased in four, and the bleeding time was prolonged in three. Analysis of vWF multimeric structure by agarose gel electrophoresis, including a newly developed high-resolution technique, demonstrated that the main band of each multimer was present, but a second, well-defined band always seen in normal individuals was missing in the patients. Two additional bands had altered mobility and were less well defined than in normal subjects, and a fifth, less intense band was also undetectable in the patients. Treatment with 1-deamino-8-D-arginine vasopressin (DDAVP) was assessed in two patients. It caused the circulating levels of vWF to increase and correct the bleeding time, but did not alter the structural abnormality. This study describes, therefore, a new variant form of Type I von Willebrand disease with aberrant structure of individual repeating multimers and an associated functional abnormality of vWF. In keeping with previously accepted terminology, the designation of Type IC von Willebrand disease has been adopted for this new variant.     

Analysis of transnasal endoscopic versus transseptal microscopic approach for excision of pituitary tumors

BACKGROUND： The traditional method of pituitary tumor excision is transseptal microscopic excision; however, the transnasal transsphenoidal endoscopic approach has shown comparable results with the transseptal microscopic approach at some institutions. The objective of this study is to compare the two types of sellar and parasellar mass resection： transnasal transsphenoidal endoscopic excision versus transseptal microscopic excision. METHODS： A retrospective cohort analysis was performed on subjects who were referred to a tertiary hospital for surgical management of sellar or parasellar masses. The two groups of patients either underwent a transnasal endoscopic approach with endoscopic excision or transseptal microscopic excision.