Tunnel capillaries in hypertrophied myocardium of rats with aorto-caval fistula

Summary Male inbred rats (Wag) with aorto-caval fistula were used as a model of volume-overloaded heart hypertrophy. Hearts were taken after 1, 2, and 6 months postoperatively for immunohistochemical, histological and ultrastructural investigations. Immunohistochemical staining with some anti-extracellular matrix antibodies and ultrastructural findings allowed us to recognize intracardiocytic tunnels which were intracellular invaginations of plasmalemma surrounded by basement membrane. Inside the tunnels endothelial cells forming well-developed capillaries were entrapped. Tunnel capillary formation is discussed as an adaptive response to increased cardiac work due to volume overload.Supported in part by the funds of the Medical Academy of Warsaw     

Abnormal expression of heparan sulfate proteoglycan on basal lamina of muscle fibers in two Japanese patients with adhalin deficiency

We recently reported the selective reduction of the BI subunit of laminin in two Japanese patients with adhalin deficiency. We here investigated immunohistochemically the expression of other components of the extracellular matrix (ECM), including collagen type IV, heparan sulfate proteoglycan (HSPG), chondroitin-4-sulfate proteoglycan, decorin, and fibronectin in adhalin deficiency, compared with other types of muscular dystrophy. We found a reduction of HSPG on the basal lamina surrounding each muscle fiber in adhalin deficiency compared with HSPG in other diseases. This finding may be characteristic evidence of the disturbance of the sarcolemma-ECM interaction and the sarcolemmal instability in adhalin deficiency. Recently, a direct role of HSPG in fibroblast growth factor (FGF) signal transduction was demonstrated. Further investigation is required to determine if the dysfunction of FGF is relevant to the pathogenesis of adhalin deficiency.     

The hypogastric and thirteenth thoracic ganglia of the rat: effects of age on the neurons and their extracellular environment

Morphometric analyses of the neurons and microvessels of perfusion-fixed hypogastric (HG) and 13th thoracic (T13) ganglia have been performed in male Wistar rats aged 4, 24 and 30 mo. Estimations of HG volume employing the Cavalieri principle have also been performed and showed that the size of the aged HG is increased by 42%. Routine histological staining of the ganglia with Masson's trichrome indicated that this may be due to the increased amount of interstitial connective tissue which was apparent in the aged animals. The number of neurons per unit area progressively decreased by 38% between ages 4 and 24 mo and by 16% between ages 24 and 30 mo in the HG and by 25% (4 and 24 mo) and 2% (24 and 30 mo) in the T13 ganglion. The total number of neurons in the HG however, estimated by a physical disector analysis, was constant with age. The number of microvessels per unit area, microvessel diameter, neuronal and nuclear areas did not differ significantly between the 3 age groups studied. This observed increase in ganglionic volume and decrease in neuronal packing density may be associated with changes in the extracellular matrix, in particular in glycosaminoglycans whose presence was indicated by metachromasia of the ganglia with toluidine blue. The extracellular matrix was therefore characterised using a panel of monoclonal antibodies against glycosaminoglycans and laminin. Chondroitin-6 sulphate and chondroitin-4 sulphate were present in the interstitial connective tissue, and there was an increase in the expression of both these epitopes at 24 mo, noteably surrounding neuron cell bodies. The expression of chondroitin-4 sulphate/dermatan sulphate was unchanged, thus implying a decreased expression of dermatan sulphate with age. Keratan sulphate and the native chondroitin sulphate epitopes were absent from the ganglia at both ages. Laminin expression was increased in the aged ganglia. It is therefore clear that the constituents of the extracellular matrix are not constant throughout the adult lifespan and that the extracellular matrix may influence neuronal survival in old age. This is the first report characterising age-related changes in the extracellular matrix of autonomic ganglia.     

肝纤维化指标联合检测在肝病诊断中的临床应用

目的探讨肝纤维化指标联合检测在肝病中的应用价值。方法采用放免法对144例肝病患者进行IV－C、HA、LN检测，并与30例献血员作对照组．统计学处理采用t检验和X2检验。结果重症肝炎、肝炎肝硬化血清IN-C、HA和LN水平和慢性肝炎（中、重度）患者血清IV—C和HA较对照组均明显升高（P＜0．001），肝硬化较慢性肝炎（中、重度）3项肝纤维化指标明显升高（P＜0．05）。肝硬化、重型肝炎和慢性肝炎（中、重度）3项指标同时检出率分别为88．9％、80％和70．8％。结论血清W—C、HA、LN联合检测对肝病的诊断及预后的判断有重要意义。病毒性肝炎患者肝纤维化血清学指标3项同时超过正常上限时，即应抗肝纤维化治疗。     

人胃癌组织中层粘连蛋白的免疫组织化学研究

对62例胃癌组织进行层粘连蛋白(Laminin)免疫组化研究的结果显示:胃癌组织中Laminin的含量和分布与胃癌的组织学类型、大体类型、组织学生长方式密切相关,胃癌细胞合成Laminin的能力与其浸润能力呈负相关。提示Laminin的减少或丢失以及分布的异常可作为胃癌细胞具有较强浸润扩散能力的生物学指标。     

Immunohistochemical localization of laminin in the basement membranes of normal, hyperplastic, and neoplastic human prostate

We examined the effects of fixatives and antibody sources on the immunohistologic localization of laminin in normal and cancer-containing human prostates and studied the localization patterns in carcinomas of varying degrees of histologic differentiation. Two different polyclonal antibodies were localized in paraffin-embedded or cryostat sections of fixed (alcohol, formalin, and paraformaldehyde) or unfixed tissue, using the immunofluorescence (IF) or immunoperoxidase (IP) techniques, with positive and negative controls. We found that the IF reactions were more intense in unfixed or alcohol-fixed sections than in paraformaldehyde-fixed specimens. IP reactions were very weak or absent in fixed and paraffin-embedded sections, but pepsin treatment of these sections resulted in more intense and uniform IP reaction products, stronger than in unfixed or ethanol-fixed cryostat sections. With the IP technique, laminin localization was intense and uniform in the basement membranes (BM) of acini, blood vessels, smooth muscle, and nerve fibers in normal prostate, benign hyperplasia (BPH), and well-differentiated carcinomas. The BM of poorly differentiated carcinomas showed widespread absence of laminin reactivity. In normal BPH and well-differentiated tumors, occasional epithelial cells and their surface and acinar lumina had laminin reactivity. However, in higher grade tumors, numerous neoplastic cells had laminin reactivity in cytoplasm, their surface, and secretory material. Some macrophages and neutrophils also contained laminin reactivity, presumably of degraded laminin. In some moderately and poorly differentiated tumors, the BM of small capillaries did not contain laminin. The BM of larger vessels always had laminin reactivity, even in the higher grade tumors.     

层粘连蛋白和纤维粘连蛋白在过量维生素A酸致心脏畸形中的作用:免疫组织化学研究

维生素A酸是常见的一类化学致畸因子,可引起各种心脏畸形,如主动脉骑跨、室间隔缺损等.实验采用免疫组织化学方法观察层粘连蛋白和纤维粘连蛋白在心脏正常和异常发育过程中的分布和变化规律,以探讨过量维生素A酸致心脏畸形发生的机理.结果显示:心内膜垫形成之前,心内膜细胞基底面呈层粘连蛋白和纤维粘连蛋白阳性;当内膜细胞转化为内膜垫细胞时,其基底面的层粘连蛋白和纤维粘连蛋白消失,心胶质和心肌膜中层粘连蛋白、纤维粘连蛋白免疫组化染色明显增强;心内膜垫形成并融合后,其染色又明显减弱.给孕鼠灌服过量的维生素A酸18小时后,各时间组胚胎心脏的心内膜、心胶质、心肌膜的层粘连蛋白和纤维粘连蛋白均出现了不同程度的减弱.这说明层粘连蛋白和纤维粘连蛋白是内膜垫细胞粘着和迁移的主要介导物质,维生素A酸抑制其两者的合成是引起心脏畸形的一个重要途径.     

Autoantibodies in the sera of Trypanosoma cruzi-infected individuals with or without clinical Chagas disease

Variations in the levels and the specificities of autoantibodies directed against a panel of antigens (cytoskeleton proteins, DNA, laminin) were analyzed in the sera from two groups of humans infected with Trypanosoma cruzi. One group was constituted of apparently healthy blood donors (BD) and the other of patients with clinically confirmed Chagas disease (CCH). In both infected groups, a high proportion but not all sera exhibited dramatic enhancement of IgM and IgG autoantibodies directed against all antigens tested. Sera positive for IgG autoantibodies were generally found more frequently in the CCH than in the BD group, except for anti-actin antibodies more often present in BD sera. Anti-laminin IgG antibodies were present in a similar number of individuals in both groups. Although the titers of anti-laminin IgG antibodies were in general higher in CCH, their dissociation constants were in the same range (7 × 10^?8–10^?7M) in both groups. IgG autoantibodies were demonstrated to be polyreactive with laminin and other self antigens as well. Circulating immune complexes were present in sera from both groups and the activity of the antibodies dissociated from these complexes was directed against all the antigens of the panel. Although the IgE concentration was significantly enhanced in several subjects from both groups, the incidence of positive sera was higher in the CCH (60%) than in the BD (39%) group. Our results demonstrate that autoantibodies with the characteristics of natural autoantibodies are found in both T. cruzi-infected apparently healthy individuals and patients. © 1993 Wiley-Liss, Inc.     

Neuronal migration in cerebellar microcultures is inhibited by antibodies against a neurite outgrowth domain of laminin.

The functional role of laminin in neuronal migration was investigated by using polyclonal antibodies or their divalent (Fab')2 fragments to a neurite outgrowth promoting domain of the B2 chain of laminin in a cerebellar microculture system widely recognized as a model for neuronal migration. We show here that these antibodies or their (Fab')2 fragments totally inhibit migration of the mouse cerebellar granule cells along the glial and other neuronal cell processes. Antibodies to native laminin or other control antibodies have no inhibitory effect. Immunocytochemical analysis of the cerebellar microcultures indicates that the functional role of these antibodies may relate to the fact that the punctate deposits of laminin and its neurite outgrowth promoting domain accumulate in between the migrating neurons and the glial cells. These data provide the first direct evidence for the functional role of laminin and its neurite outgrowth domain in neuronal migration in the mammals. They further suggest that a neuronal cell surface contact with the extracellular deposits of a neurite outgrowth domain of the B2 chain of laminin may mediate neuronal-glial interactions.     

血清透明质酸与层粘连蛋白的联合检测在急、慢性肝病中的作用

目的：探测血清透明质酸（HA）与层粘连蛋白（LN）的联合检测在急、慢性肝病中的作用。方法：采用放射免疫法测定正常对照组18例及急、慢性肝病患者76例HA、LN的含量，结果76例急、慢性肝病患者血清HA、LN与正常对照比较，差异有显著性（P〈0．01）。结论：以HA、LN为实验参考指标，对尽早发现慢性肝病向肝硬化转化起到早预防、早诊治的作用。