Persistent GAD 65 antibodies in longstanding IDDM are not associated with residual beta-cell function, neuropathy or HLA-DR status

Persistent humoral autoimmunity to the enzyme glutamic acid decarboxylase (GAD) has been described in a substantial proportion of patients with insulin-dependent diabetes mellitus (IDDM) of long duration. The source of the stimulus for this autoimmune reactivity is still unknown. Because the GAD 65 isoform is mainly expressed in pancreatic beta-cells and in the nervous system we investigated in the present study of the largest number of well characterized patients with longstanding IDDM (n = 105; median duration: 21 years; range: 10-46 years) the presence of autoantibodies to GAD 65 and their relationship to a residual C-peptide response or peripheral and autonomic neuropathy. Additionally we studied the HLA-DR status relative to GAD 65 antibodies in 86 out of the 105 individuals. One hundred healthy control subjects and 100 recent onset IDDM patients were also studied for GAD 65 antibodies. GAD 65 antibodies were detected in a radioligand-binding-assay with recombinant human GAD 65 and were present in 32% of the long-term diabetic patients, 82% of the recent onset IDDM patients and in 3% of the healthy control subjects. A preserved C-peptide response to i.v. glucagon (Hendriksen criteria) was observed in 23% of the long-term IDDM patients. Autonomic neuropathy and peripheral neuropathy was identified using criteria based on both symptoms and formal testing giving a frequency of 67% vs 79%. The HLA specific DR 4/X was observed in 47% and HLA-DR 3/X in 22% of the long-term IDDM patients. Patients who were heterozygous for DR3/DR4 were found in 23% of the cases. GAD 65 antibodies were significantly less frequent in the long-term IDDM patients compared to recent onset IDDM (p < 0.001), and diabetes duration showed a significant negative correlation with GAD 65 antibody index levels (r = 0.22, p < 0.01). Interestingly, GAD 65 antibodies were not significantly correlated either with residual beta-cell function or neuropathy and no particular HLA-DR status was associated with persistent GAD 65 antibodies. In conclusion neither residual beta-cell function nor diabetic neuropathy or a certain HLA-DR specificity are exclusively associated with persistent autoimmunity directed to GAD 65 in longstanding IDDM. The stimulus for the persistent humoral immune response and its significance for the disease process and its complications remain to be established.     

金属镱低压吸氘研究

在真空系统中的氘压低于0.1 MPa条件下研究了金属镱的吸氘性能,并对不同原子比的氘化物的物相进行了分析.在常压、300 ℃下,金属镱吸氘不明显;400 ℃时,金属镱经较长时间活化后吸附一定量的氘;500 ℃时,镱升华.400 ℃时的吸氘实验结果表明:从活化至开始吸氘直至吸附平衡需很长时间;氘/镱原子比的高低与吸氘时间有关,饱和吸氘时的原子比最大为2.00;金属镱为面心立方(fcc)结构,a0=0.549 2 nm.具有不同原子比的氘化镱的X射线衍射(XRD)分析结果显示:氘化镱有2种结构,即面心立方结构(a0=0.524 nm)和正交结构(a0=0.588 nm、b0=0.358 nm、c0=0.678 nm);金属镱吸氘后,立方结构氘化镱晶格常数及晶胞体积均发生收缩现象,收缩率分别约为4%和11%.正交结构氘化镱晶胞体积收缩约14%.     

Fetal heart rate following coelocentesis

For psychological reasons, coelocentesis was performed in 20 women prior to termination of pregnancy, at 6-11 weeks of gestation. The fetal heart rate (FHR) was measured immediately before the procedure and at 1, 5, and 10 min afterward. There was no significant difference between FHR before coelocentesis compared to the values at 1 min (mean = 158, range 114-178; z = -0.629, P = 0.529), 5 min (mean = 160, range 121-179; z = -0.191, P = 0.848), or 10 min (mean 159, range 117-183; z = -0.214, P = 0.83) after the procedure. These findings suggest that coelocentesis does not have a major effect on the fetal cardiovascular system.     

Consumption of reduced-fat products: effects on parameters of anti-oxidative capacity

Plasma levels of fibrinogen, factor VIIc and prothrombin fragment F1 + 2, a marker of thrombin generation in vivo, were studied in 68 subjects with serum total cholesterol (TC) levels between 135 and 349 mg/dl but without clinical evidence of cardiovascular disease and other atherosclerotic risk factors. F1 + 2 plasma levels were directly correlated with TC (p < 0.0004), low-density lipoprotein cholesterol (LDL-C; p < 0.0018) and factor VIIc (p < 0.024). Thirty-five subjects with TC greater than 249 mg/dl (median value of the whole group) showed higher levels of F1 + 2 (p < 0.0001) and fibrinogen (p < 0.0015) than those with TC lower than 249 mg/dl. In subjects with TC > 249 mg/dl and F1 + 2 > 1.2 nM (median value of the whole group), a cholesterol-lowering drug (simvastatin) was able to reduce F1 + 2 (p < 0.009) as well as TC and LDL-C. This study shows a relationship between serum cholesterol and the rate of thrombin generation supporting the hypothesis that a hypercoagulable state may occur in hypercholesterolemic subjects before the onset of clinical evidence of atherosclerotic cardiovascular disease.