An extended association screen in multiple sclerosis using 202 microsatellite markers targeting apoptosis-related genes does not reveal new predisposing factors

Apoptosis, the programmed death of cells, plays a distinct role in the etiopathogenesis of Multiple sclerosis (MS), a common disease of the central nervous system with complex genetic background. Yet, it is not clear whether the impact of apoptosis is due to altered apoptotic behaviour caused by variations of apoptosis-related genes. Instead, apoptosis in MS may also represent a secondary response to cellular stress during acute inflammation in the central nervous system. Here, we screened 202 apoptosis-related genes for association by genotyping 202 microsatellite markers in initially 160 MS patients and 160 controls, both divided in 4 sets of pooled DNA samples, respectively. When applying Bonferroni correction, no significant differences in allele frequencies were detected between MS patients and controls. Nevertheless, we chose 7 markers for retyping in individual DNA samples, thereby eliminating 6 markers from the list of candidates. The remaining candidate, the ERBB3 gene microsatellite, was genotyped in additional 245 MS patients and controls. No association of the ERBB3 marker with the disease was detected in these additional cohorts. In consequence, we did not find further evidence for apoptosis-related genes as predisposition factors in MS.     

Co-administration of a DNA vaccine encoding the prostate specific membrane antigen and CpG oligodeoxynucleotides suppresses tumor growth

BACKGROUND: Prostate-specific membrane antigen (PSMA) is a well characterized prostate-specific tumor associated antigen. Its expression is elevated in prostate carcinoma, particularly in metastatic and recurrent lesions. These observations suggest that PSMA can be used as immune target to induce tumor cell-specific recognition by the host and, consequently tumor rejection. We utilized a DNA-based vaccine to specifically enhance PSMA expression. An immune modulator, such as CpG oligodeoxynucleotides which promote Th1-type immune responses was combined to increase the efficacy of tumor recognition and elimination. METHODS: A eukaryotic expression plasmid pCDNA3.1-PSMA encoding full-length PSMA was constructed. C57BL/6 mice were immunized with endotoxin-free pCDNA3.1-PSMA alone or in combination with CpG oligodeoxynucleotides by intramuscular injection. After 4 immunizations, PSMA specific antibodies and cytotoxic T lymphocyte reactivity were measured. Immunized C57BL/6 mice were also challenged subcutaneously with B16 cells transfected with PSMA to evaluate suppression of tumor growth. RESULTS: Vaccine-specific cytotoxic T lymphocytes reactive with B16 cells expressing PSMA could be induced with this treatment schedule. Immune protection was observed in vaccinated mice as indicated by increased tumor growth in the control group (100%) compared with the groups vaccinated with DNA alone (66.7%) or DNA plus CpG oligodeoxynucleotides (50%) respectively. Average tumor volume was smaller in vaccinated groups and tumor-free survival time was prolonged by the vaccination. CONCLUSION: The current findings suggest that specific anti-tumor immune response can be induced by DNA vaccines expressing PSMA. In addition, the suppression of in vivo growth of tumor cells expressing PSMA was augmented by CpG oligodeoxynucleotides. This strategy may provide a new venue for the treatment of carcinoma of prostate after failure of standard therapy.     

Detection of circulating Aspergillus fumigatus galactomannan: value and limits of the Platelia test for diagnosing invasive aspergillosis

The effectiveness of galactomannan detection with the Platelia test was evaluated in a prospective study of 3,327 sera from 807 patients. The specificity was 99.6% (748 of 751 cases). For the groups of patients with proven and probable invasive aspergillosis, the sensitivity was 50.0% (17 of 34 cases). The disappointing sensitivity associated with the presence of rare false-positive cases underlines the limits of this test.     

Postsynaptic action of BDNF on GABAergic synaptic transmission in the superficial layers of the mouse superior colliculus

The neurotrophin brain-derived neurotrophic factor (BDNF) is involved in numerous aspects of synapse development and plasticity. The present study was aimed at clarifying the significance of endogenous BDNF for the synaptically driven spontaneous network activity and GABAergic inhibition in the superficial layers of the mouse superior colliculus. In this structure neuron survival is unaffected by the absence of BDNF. Two experimental approaches were used: comparison of BDNF-deficient (-/-) and wild-type (+/+) mice and blockade of BDNF receptor signaling by the tyrosine kinase inhibitor K-252a. Patch-clamp recordings were performed on horizontal slices during postnatal days 15 and 16. The lack of BDNF in -/- mice caused a significant reduction of the spontaneous action potential frequency and an increase in the pharmacologically induced disinhibition of spike discharge. This change was accompanied by an increase in the amplitudes of GABAergic evoked, spontaneous, and miniature inhibitory postsynaptic currents (IPSCs). BDNF gene inactivation had no effect on the degree of paired-pulse facilitation or the frequency of miniature IPSCs. The increase of IPSC amplitudes by chronic BDNF deprivation was completely mimicked by acute exposure to K-252a in +/+ animals. The enhancement of GABAergic IPSCs in -/- animals was reversed by acute application of 100 ng/ml BDNF, but this rescue was completely prevented by blocking postsynaptic protein kinase C (PKC) activation with the PKC inhibitor peptide 19-31. From these results we conclude that BDNF increases spontaneous network activity by suppressing GABAergic inhibition, the site of action of BDNF is predominantly postsynaptic, BDNF-induced suppression of GABAergic synaptic transmission is caused by acute downregulation of GABA(A) receptors, and BDNF effects are mediated by its TrkB receptor and require PKC activation in the postsynaptic cell.     

甲状腺疾病患者血清可溶性白细胞介素2受体测定的临床意义

某些甲状腺疾病时血清可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）水平及其与游离甲状腺素（ＦＴ＿４）、游离三碘甲腺原氨酸（ＦＴ＿３）和促甲状腺素（ＴＳＨ）水平的相关性比较。结果发现甲状腺机能亢进症（甲亢）未治疗组（Ａ）及甲亢未治疗伴突眼组（Ｄ）血清ｓＩＬ－２Ｒ明显升高；甲状腺机能减退症（甲减）经治疗甲状腺功能灭常组（Ｇ）ｓＩＬ－２Ｒ明显高于甲减未治疗组（Ｆ）；１０例毒性弥漫性甲状腺肿（Ｇｒａｖｅｓ病）患者经抗甲状腺药物治疗后ｓＩＬ－２Ｒ明显降低；Ｇｒａｖｅｓ病及甲减患者血清ｓＩＬ－２Ｒ均与ＦＴ＿３呈正相关。提示除自身免疫外，甲状腺素水平也是甲状腺疾病患者血清ｓＩＬ－２Ｒ水平的重要调节因素。     

PPARgamma knockdown by engineered transcription factors: exogenous PPARgamma2 but not PPARgamma1 reactivates adipogenesis.

To determine functional differences between the two splice variants of PPARgamma (gamma1 and gamma2), we sought to selectively repress gamma2 expression by targeting engineered zinc finger repressor proteins (ZFPs) to the gamma2-specific promoter, P2. In 3T3-L1 cells, expression of ZFP55 resulted in >50% reduction in gamma2 expression but had no effect on gamma1, whereas adipogenesis was similarly reduced by 50%. However, ZFP54 virtually abolished both gamma2 and gamma1 expression, and completely blocked adipogenesis. Overexpression of exogenous gamma2 in the ZFP54-expressing cells completely restored adipogenesis, whereas overexpression of gamma1 had no effect. This finding clearly identifies a unique role for the PPARgamma2 isoform.     

Proteomic analysis of salt-sensitive outer membrane proteins of Vibrio parahaemolyticus

Vibrio parahaemolyticus, a universal marine pathogen with available genome sequences, could be used as a bacterial model to clarify the various physiological phenomena of its native and host environments. In the present study, proteomic methodologies were applied to investigate the expression pattern of outer membrane proteins (OMPs) of V. parahaemolyticus at different NaCl concentrations. OmpW, OmpV, elongation factor TU and polar flagellin were determined to be osmoregulation-sensitive OMPs, among which OmpW and OmpV were reported to vary with changed NaCl concentrations in the pattern of osmolarity regulation. Therefore, our results not only expand our knowledge on osmoregulation-related proteins, but also provide a valuable strategy for the screening of salt-sensitive proteins.     

职业紧张与冠心病的病例对照研究

目的 :(1)探讨男性列车乘务人员职业紧张与冠心病发病的关系。方法 :应用职业紧张因素测试量表 (OSI) ,对男性列车乘务人员中 3 9例冠心病患者进行 1:2的配比病例对照研究并进行多因素条件Logistic回归分析。结果 :(1)在控制和考虑了非职业紧张因素条件下 ,职业紧张与冠心病关系密切 (OR =2 18,95 %CI :1 15 -4 15 ) ,而且随着职业紧张程度的增加 ,患冠心病的危险性显著增加 ;(2 )以铁路乘务人员为对照时 (与病例同工种 ) ,职业紧张仍与冠心病发病有关联 (OR =4 43 ,95 %CI :1 60 -12 2 5 ) ,但其OR值明显低于以其他服务行业人员为对照时的OR值 (OR =9 75 ,95 %CI:3 18-2 9 92 )。结论 :职业紧张是引起男性列车乘务人员冠心病发病的重要危险因素之一。     

The New Millennium Palliative Care Project (2000-2003): the impact of specialised GP advisors.

This study describes a novel type of support for GPs caring for patients dying at home: the establishment and evaluation of a telephone advisory service for GPs, run by GPs with a special interest in palliative care (GPwSIs) in the Netherlands 2000-2003. A growing number of GPs called for advice, 10% during out of hours. Prognosis of the patients was generally short (days to weeks in 70% of cases). Most advice sought by GPs concerned symptom management and on evaluation, 85% of the GPs followed the advice.     

Characterization of a novel HLA-DQB1 allele, DQB1*020102

A novel human leukocyte antigen (HLA)-DQB1 allele, DQB1*020102, was detected in a 28-year-old woman of Han ethnic in Guangzhou, China. Compared with HLA-DQB1*020101 and HLA-DQB1*0202, they differed in only one nucleotide at the position 167 (C to T) of exon 2, which was a highly conserved position. This is a synonymous mutation, which does not cause any change in the amino acid sequence of mature protein.