经皮腔内室间隔心肌消融术对心电指标的影响

目的研究肥厚梗阻型心肌病患者经皮腔内室间隔心肌消融术对心电指标的影响。方法对50例肥厚梗阻型心肌病患者行经皮腔内室间隔心肌消融术,记录术前、术中和术后出现的心律失常类型,配对分析术前、术后心电指标的变化。结果术后与术前相比,QRS时限[(122.0±24.0)ms对(97.3±15.5)ms,P=0.000]明显延长,QTc[(469.3±32.2)ms对(434.3±41.5)ms,P=0.004]、PR间期[(169±26)ms对(162±24)ms,P=0.044]稍延长。术中心律失常发生率分别为:右束支传导阻滞70%(35/50),左束支传导阻滞8%(4/50),一过性AVB38%(19/50),频发室性早搏24%(12/50),短阵室性心动过速24%(12/50);未发生持续性室性心动过速和室颤。术后心律失常发生率分别为:右束支传导阻滞56%(28/50),左束支传导阻滞8%(4/50),交界区性心动过速4%(2/50),频发室性早搏16%(8/50),短阵室性心动过速8%(4/50)。无永久性起搏器植入及死亡病例。结论经皮腔内室间隔心肌消融术致心律失常的发生率高,右束支传导阻滞最为常见。严格选择适应证后谨慎地行PTSMA术是安全、可行的。     

Anti-mitochondrial antibodies (anti-M7) in heart diseases recognize epitopes on bacterial and mammalian sarcosine dehydrogenase.

The anti-mitochondrial antibody (AMA) anti-M7 has been shown to occur exclusively in sera from patients with acute and chronic myocarditis. Applying different enzymes of the inner mitochondrial membrane to ELISA, anti-M7-positive sera reacted only with sarcosine dehydrogenase (SD) from Pseudomonas aeruginosa. Testing these sera in the Western blot against a commercially available SD as well as against SD prepared from rat liver mitochondria, a determinant at 42 kD and 90 kD, respectively, was visualized. Using submitochondrial particles (SMP) from bovine heart and rat liver another major determinant at 64 kD could be observed with both antigen fractions. Liver SMP also expressed the SD-related, 90-kD epitope. Sera from patients with other AMA-positive and AMA-negative autoimmune diseases were negative with these different determinants. The identity of the 64-kD epitope on heart and liver SMP as well as the 42-kD polypeptide of bacterial SD and the 90-kD epitope on mammalian SD was proven by absorption studies and by elution of antibodies from the antigen bound to the immobilon sheets after immunoblotting. The SD enzyme activity was not affected by anti-64-kD and anti-42-kD antibodies in vitro. It is concluded that anti-M7 antibodies may be stimulated by an antigen expressed on cardiocytes during an infection which shares epitopes with SD, an evolutionary highly conserved protein. SD-sensitized B cell clones could therefore be triggered by the M7-antigen which shows homology to SD.     

2型糖尿病肾病患者血清胱抑素C的检测及意义

目的:检测糖尿病患者血清胱抑素C浓度变化,分析其在糖尿病患者早期肾损伤中的作用。方法:根据24h尿白蛋白排泄率(UAER)的测定结果,将104例糖尿病患者分为3组:单纯糖尿病组(SDM组)、早期糖尿病肾病组(EDN组)和临床糖尿病肾病组(CDN组);46名健康者作对照组;采用颗粒增强散射免疫比浊法测定血清胱抑素C水平,常规测定内生肌酐清除率、血肌酐和UAER,并对全部患者胱抑素C血清浓度与尿UAER进行直线相关分析。结果:SDM组,EDN组及CDN组间血清胱抑素C水平均有非常显著性统计学意义(P<0.01),血清胱抑素C与UAER、内生肌酐清除率及血肌酐值有良好相关性(r值分别为0.772,-0.754,0.785,P均<0.01)。结论:血清胱抑素C水平测定有助于2型糖尿病肾病的早期诊断,优于血肌酐和内生肌酐清除率,具有临床应用价值。     

SGK1在糖尿病小鼠肾脏皮质中时间差异性表达及意义

目的：研究血清和糖皮质激素诱导的蛋白激酶1（serum and glucocorticoid-inducible kinase 1,SGK1）在糖尿病（DM）小鼠肾脏皮质中时间上差异性表达及意义。方法: 采用链脲佐菌素（STZ）单次腹腔注射诱导小鼠糖尿病模型。将2月龄C57BL/6小鼠随机分成10组：第1、2、3、4、6、8、12周糖尿病小鼠组（DM₁、DM₂、DM₃、DM₄、DM₆、DM₈、DM₁₂）和相应的第1、4、8周正常对照组（N₁、N₄、N₈）。分别在DM模型制作成功后第1、2、3、4、6、8、12周末收集小鼠24 h尿量，检测24 h尿蛋白量；观察肾脏病理改变；半定量RT-PCR检测小鼠肾脏皮质SGK1及结缔组织生长因子（CTGF）mRNA的表达，Western blotting检测N₄、DM₄、DM₈组皮质SGK1、CTGF蛋白的表达。结果: 随着糖尿病病程的进展，DM组小鼠肾小球体积逐渐增大、系膜区逐渐增宽；DM组小鼠24h尿蛋白从第2周起开始逐渐增多，肾脏皮质SGK1 mRNA表达从第2周开始明显上调，在第４周达到峰值。CTGF随着糖尿病病程的进展表达逐渐递增。结论: SGK1在糖尿病早期肾脏表达峰值的出现及CTGF 持续递增的表达，提示SGK1在糖尿病肾病肾脏纤维化的发生发展过程中起重要作用。     

The haplotype block, NFKBIL1-ATP6V1G2-BAT1-MICB-MICA, within the class III-class I boundary region of the human major histocompatibility complex may control susceptibility to hepatitis C virus-associated dilated cardiomyopathy

Cardiomyopathy is a heart muscle disease with impaired stretch response that can result in severe heart failure and sudden death. A small proportion of hepatitis C virus (HCV)-infected patients may be predisposed to develop dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). The molecular mechanisms involved in the predisposition remain unknown due in part to the lack of information on their genetic background. Because the human leukocyte antigen (HLA) region has a pivotal role in controlling the susceptibility to HCV-induced liver disease, we hypothesized that particular HLA alleles and/or non-HLA gene alleles within the human major histocompatibility complex (MHC) genomic region might control the predisposition to HCV-associated DCM (HCV-DCM) and/or HCV-associated HCM (HCV-HCM). Here, we present mapping results of the MHC-related susceptibility gene locus for HCV-associated cardiomyopathy by analyzing microsatellite and single nucleotide polymorphism markers. To delineate the susceptibility locus, we genotyped 44 polymorphic markers scattered across the entire MHC region in a total of 59 patients (21 HCV-DCM and 38 HCV-HCM) and 120 controls. We mapped HCV-DCM susceptibility to a non-HLA gene locus spanning from NFKBIL1 to MICA gene loci within the MHC class III-class I boundary region. Our results showed that HCV-DCM was more strongly associated with alleles of the non-HLA genes rather than the HLA genes themselves. In addition, no significant association was found between the MHC markers and HCV-HCM. This marked difference in the MHC-related disease susceptibility for HCV- associated cardiomyopathy strongly suggests that the development of HCV- DCM and HCV-HCM is under the control of different pathogenic mechanisms.     

Pathological analysis of hypertrophic cardiomyopathy simulating dilated cardiomyopathy

The pathomorphologic features of hypertrophic cardiomyopathy simulating dilated cardiomyopathy in the late stage (HCM-DCM) were compared with those of ordinary hypertrophic cardiomyopathy (HCM). Seven autopsied hearts with HCM-DCM and 11 with HCM were assessed quantitatively using an image analyzer. Unlike HCM, significant left ventricular enlargement and wall thinning were observed in HCM-DCM, and the percentage areas of massive fibrosis and disarray were significantly greater. In HCM-DCM, the disarray was distributed diffusely, whereas massive fibrosis was distributed more intensively in the ventricular septum and anterior wall than in the lateral and posterior wall. Narrowing of intramyocardial small arteries was observed more frequently in HCM-DCM, especially in the ventricular septum and anterior wall, than in HCM. These results suggest that the enlargement and wall thinning of the left ventricle in HCM-DCM are attributable to non-uniform progression of massive fibrosis, which is closely related to small-arterial lesions.     

Anti-mitochondrial flavoprotein autoantibodies of patients with myocarditis and dilated cardiomyopathy (anti-M7): interaction with flavin-carrying proteins, effect of vitamin B2 and epitope mapping

Vitamin B2 and flavin cofactors are transported tightly bound to immunoglobulin in human serum. We reasoned that anti-mitochondrial flavoprotein autoantibodies (alpha Fp-AB) present in the serum of patients with myocarditis and cardiomyopathy of unknown aetiology may form immunoglobulin aggregates with these serum proteins. However, immunodiffusion and Western blot assays demonstrated that the flavin-carrying proteins were not recognized by alpha Fp-AB. Apparently the flavin moiety in the native protein conformation was inaccessible to alpha Fp-AB. This conclusion was supported by the absence of an immunoreaction between the riboflavin-binding protein from egg white and alpha FP-AB. Intravenous application of vitamin B2 to rabbits immunized with 6-hydroxy-D-nicotine oxidase, a bacterial protein carrying covalently attached FAD, did not neutralize alpha Fp-AB which had been raised in the serum of the animals. FAD-carrying peptides generated from 6-hydroxy-D-nicotine oxidase by trypsin and chymotrypsin treatment were not recognized by the alpha Fp-AB, but those generated by endopeptidase Lys were. This demonstrates that the epitope recognized by alpha Fp-AB comprises, besides the flavin moiety, protein secondary structure elements.     

Alterations of glomerular matrix proteins in the pathogenesis of diabetic nephropathy

Summary Diabetic late complications are characterized by morphological and biochemical alterations of the extracellular matrix. In particular, longstanding diabetes causes quantitative and qualitative changes in basement membrane structure of retinal and renal capilleries. Immunohistochemical investigations of diabetic kidneys with diffuse glomerulosclerosis show increased collagen type IV deposition in the mesangial matrix and decreased heparan sulfate proteoglycan content in the mesangial matrix and glomerular basement membrane as well. In nodular glomerulosclerosis normal basement membrane components are decreased or absent while the occurrence of collagen type III in this stage has been interpreted as an irreversible alteration of the glomerular structure. These changes seem to be the underlying cause for the alterations in renal functions like persistent albuminuria and proteinuria. Increased intra- and extracellular levels of glucose and its derivatives are thought to be responsible for diabetic tissue dysfunction although there are reports on possible genetic defects causing increased susceptibility to develop diabetic nephropathy. Recent results, however, focuse on the role of glucose-induced cytokine secretion as mediator for altered metabolism of glomerular matrix proteins. In vitro studies with cultured kidney cells have shown that the glucose-induced dysregulation of the basement membrane synthesis may be mediated by a glucose dependent activation of protein kinase C. Alternatively or synergistically, the formation of AGE products formed after prolonged exposure of matrix proteins to elevated glucose may also lead to cytokine secretion subsequently inducing synthesis of extracellular matrix proteins. Studies in experimental animals confirm the diabetes induced dysregulation of the synthesis of extracellular matrix components on the molecular level.Abbreviations HSPG heparan sulfate proteoglycan - GBM glomerular basement membrane - ECM extracellular matrix - AGE advanced glucosylation end products - TNF tumor necrosis factor - bFGF basic fibroblast growth factor     

Eosinophilic pancreatitis in the newborn infant of a diabetic mother

Summary The authors have studied the pancreas of a premature female infant born to a diabetic mother. The findings included a peri-insular eosinophilic leucocyte infiltration, macropolinesia and a marked increase in B cells. In the exocrime parenchyma small B cells aggregates were also observed. B cells contained voluminous hypercromatic muclei and degranulated cytoplasm. Morphometric data demonstrated an increase in islet tissue. These morphological findings are indicative of excessive insulin secretion. The presence of eosinophilic leucocytes in pancreatic tissue and the pathogenic mechanism involved are discussed.     

Microangiopathy in human diabetic neuropathy

Summary Morphological change of endoneurial and perineurial vessels accompanied severe loss of myelinated axons in peripheral nerves of each of 17 patients with diabetic neuropathy. Vascular mural thickening averaged 18.9±9.9 m² in diabetic capillaries (n=11) vs. 6.9±4.1 m² in controls (n=7). Electron microscopy revealed vigorous endothelial proliferation as well as thickening and reduplication of basal lamina in each instance. Particular attention was paid to vessels which penetrate the perineurium en route to the endoneurial intertitium, since they provide a major portion of the endoneurial blood supply. Luminal narrowing and mural thickening of these vessels was compounded by basal laminar thickening of the perineurium. Fenestrated endoneurial capillary endothelium was noted in one case. Both demyelination and axonal degeneration were observed with intra-axonal glycogen accumulation in some axons. Morphometric analysis revealed extensive myelinated nerve fiber loss in diabetic nerves. These morphological findings emphasize the impact of diabetic microangiopathy on specialized endothelium and suggest that local anatomic factors in the perineurial sheath render the nerve vulnerable to chronic ischemia.Supported in part by the National Institute for Communicative Disorders and Stroke NS-14162 and by the Veterans Administration Research Service