Glucose-induced loss of glycosyl-phosphatidylinositol-anchored membrane regulators of complement activation (CD59, CD55) by in vitro cultured human umbilical vein endothelial cells

Aims/hypothesis. This study examines whether increased glucose concentrations are responsible for a decreased expression of membrane regulators of complement activation molecules. The effect of high glucose in determining an increase in membrane attack complex deposition on endothelial cells was also investigated. Methods. Endothelial cells were isolated from umbilical cord tissue, cultured in the presence of increased concentrations of glucose, and the expression of CD46, CD55, and CD59 was detected by ELISA (enzyme-linked immunosorbent assay) and by flow cytometry. Glucose-treated endothelial cells were also incubated with antiendothelial cell antibodies and fresh complement to assess the amount of membrane attack complex formation. Results. High concentrations of glucose decreased the expression of CD59 and CD55 by endothelial cells in a time-dependent and glucose concentration-dependent manner without affecting CD46 expression. High concentrations of soluble CD59 were found in the supernatants of cells treated with high glucose. The decrease in CD59 expression induced by high glucose concentrations was reversed by coincubation of cells with a calcium channel blocking agent (Verapamil). All of these effects were not reproduced by osmotic control media. Cells treated with concentrations of high glucose were more susceptible to complement activation and membrane attack complex formation after exposure to antiendothelial cell antibodies. Conclusion/Interpretation. We speculate that hyperglycaemia could directly contribute to a loss of CD59 and CD55 molecules through a calcium-dependent phosphoinositol-specific phospholipase C activation and subsequent regulation of cell wall expression of GPI-anchored proteins. This phenomenon could facilitate the activation of a complement pathway and could play a part in the aetiology of endothelial dysfunction in diabetes. [Diabetologia (2000) 43: 1039–1047] Received: 31 January 2000; Accepted: 8 May 2000     

Gender and racial differences in surgical outcomes among adult patients with acute heart failure

Background

Approximately three million U.S. adult women have heart failure (HF), increasing their risk of adverse perioperative outcomes. While gender and racial differences are reported in surgical outcomes, less is known about 30-day perioperative outcomes in HF patients.

结直肠癌组织中MAC30 的表达及其临床意义

 目的探讨脑膜瘤相关蛋白（MAC30）mRNA 及蛋白在结直肠癌中的表达及其临床意义。方法应用免疫组化S-P法检
测结肠癌、结肠远端正常黏膜及淋巴结转移癌中MAC30 蛋白的表达水平,并采用RT-PCR 法对结直肠癌组织、癌旁无瘤黏膜、
近端及远端切缘正常黏膜组织中MAC30mRNA 的表达进行检测。结果MAC30 在结直肠癌及淋巴结转移癌中的表达较正常
黏膜明显增强。结直肠癌组织中MAC30mRNA的表达明显高于癌旁无瘤黏膜、远端及近端切缘黏膜（ P< 0.05）,且与肿瘤的组
织学类型有关。结直肠癌中MAC30表达强阳性的患者3 年生存期较弱表达者明显缩短。结论MAC30 的高表达可能参与了
结直肠癌的发生和发展,可作为评估结直肠癌预后的一个参考指标。     

GABA(A)-R alpha1 subunit knockin mutation leads to abnormal EEG and anesthetic-induced seizure-like activity in mice

Gamma-aminobutyric acid-type A receptors (GABA(A)-Rs) have been proposed as a target for many general anesthetics. We recently created knockin (KI) mice harboring a point mutation (serine 270 to histidine) in the GABA(A)-R alpha1 subunit. This mutation abolishes sensitivity of recombinant GABA(A)-Rs to isoflurane while maintaining normal sensitivity to halothane and increasing the potency of GABA. KI mice showed abnormalities in the EEG baseline, including occasional spike-wave activity and spindle-like bursts. When anesthetized with isoflurane, the KI mice but not the control mice revealed repetitive 4-5 Hz slow wave discharges in the cortical EEG. KI mice did not differ from controls in response to isoflurane or halothane in the standard tail clamp/withdrawal and loss of righting reflex assays. We recorded miniature inhibitory postsynaptic currents (mIPSCs) from hippocampal interneurons and pyramidal cells in brain slices. mIPSCs in neurons from KI mice were of normal amplitude, but decayed more slowly than controls. Hippocampal mIPSCs in control mice were significantly prolonged by 0.4 and 0.9 MAC isoflurane, and by 0.5 MAC halothane. In KI mice, the effect of isoflurane on mIPSC decay was dramatically reduced, while halothane prolonged mIPSCs as for controls. We conclude that the kinetic and pharmacological properties of hippocampal GABA(A)-Rs in the KI mouse recapitulate many features of mutant alpha1beta2gamma2 GABA(A)-Rs observed in vitro. GABA(A)-Rs containing alpha1 subunits do not appear to contribute to the actions of isoflurane in the spinal cord, but both EEG and synaptic recordings provide evidence for effects of isoflurane on these GABA(A)-R isoforms in cortical structures.     

Comparison of a questionnaire commonly used for measuring coping with a daily-basis prospective coping measure

BACKGROUND: Much research have investigated the relation between stress and health, with focus on the role of coping as a moderator. The use of the concept of coping is in need of more stringency since it is often used in a more or less careless manner. A contributory cause of the confusion within the research field is the often-negligent interpretation of results from the Mental Adjustment to Cancer (MAC) Scale (i.e., results are discussed in terms of coping strategies instead of mental adjustment). Furthermore, checklists are often used in research but seldom specify the stressor that patients are attempting to cope with. METHODS: Consecutive patients newly diagnosed with gastrointestinal (GI) cancer were included in this study. Of 151 eligible patients, 95 (63%) participated. As soon as their physical condition so permitted, patients were asked to assess their coping by way of two methods: an instrument commonly used for measuring coping (MAC Scale) and a daily-basis prospective coping measure [Daily Coping Assessment (DCA)]. The study investigated the relations between these two methods, which are used to evaluate different ways of coping with cancer, and related these to specified stressful events and psychologic distress outcomes [Hospital Anxiety and Depression Scale (HADS)]. RESULTS: Among patients with GI cancers, a comparison of the DCA with the MAC Scale renders important differences regarding the use of coping strategies. Furthermore, coping as measured by the DCA is more clearly separated from both stressors such as psychologic aspects and psychologic distress outcomes as measured by the HADS. DISCUSSION: A comparison between the two measures renders differences regarding the use of coping strategies among patients with GI cancers. The daily-basis prospective coping measure seems to be better separated from both stressful events and psychologic distress outcomes. The DCA offers a promising alternative to the use of coping checklists. The difference between the measures is in accordance with the original intention that the MAC Scale be used to measure mental adjustment rather than coping (i.e., the results do not support the use of the MAC Scale as a coping measure).     

Susceptibility to pulmonary disease due to Mycobacterium avium–intracellulare complex may reflect low IL-17 and high IL-10 responses rather than Th1 deficiency

It remains unclear why some individuals and not others are susceptible to non-tuberculous mycobacterial lung disease (NTMLD). To determine whether NTMLD is associated with defects or biases in Th1/Th2/Th17 immunity, blood leukocytes from NTM patients with nodular bronchiectasis, their adult offspring, and healthy population controls were stimulated with staphylococcal enterotoxin B (SEB), tuberculin and sensitin to measure cytokine production. In response to SEB, NTM patients exhibited higher frequencies of IFNγ-producing CD4⁺ T cells than population controls (P < 0.001). In supernatant, levels of IL-17 were lower in patients than adult offspring. Sensitin elicited higher IFNγ responses from patients than controls (P < 0.05). Patients also produced more IL-10 in supernatant than controls after culture with tuberculin (P < 0.01) or sensitin (P < 0.05), but IL-10-producing CD4⁺ T cells were undetectable. NTMLD is not associated with deficient IFNγ production, but may be associated with reduced Th17 immunity and/or a predisposition towards IL-10 production from non-CD4⁺ T cells.     

Expression of MAC-1 (CD11b) in acute myeloid leukemia (AML) is associated with an unfavorable prognosis

There is evidence to suggest, that cellular adhesion molecules and receptors could play a role in leukemia, e.g., through altered adhesive qualities of leukemic blasts. We have studied the expression of the beta2-integrin Mac-1 (CD11b) on mononuclear cells in 48 patients with AML at first diagnosis by flow cytometry using a direct fluorescein-conjugated antibody. A case was defined as positive if more than 20% of the cells expressed Mac-1. Within the FAB types, we observed a high expression rate in cases with M5 (100% MAC-1+ cases, 73% MAC-1+ cells), M4 (75% MAC-1+ cases, 48% MAC-1+ cells) and in cases with FAB-M1 with 71% MAC-1+ cases and 29% MAC-1+ cells. Separating our patients' cohort in cytogenetic risk groups, we could detect significant higher proportions of MAC-1+, cases (88% vs. 27%, P = 0.005) and cells (51% vs. 16%, P = 0.015) with poor cytogenetic risk compared to the favorable risk group. For clinical evaluations only patients treated according to the protocols of the German AML Cooperative Group (AML-CG) were included (n = 29, cases with AML-M3 were excluded). More MAC-1+ cases and cells were found in the "non-responders" group (n = 8) compared to the "responders" group (n = 24). We can conclude that AML cases with high MAC-1 expression are characterized by a worse prognosis. Evaluation of MAC-1 expression in AML might therefore contribute clinically important data with respect to develop new therapies that influence the interactions between integrins like MAC-1 on leukemic cells and endothelial or immunoreactive cells.