[Prion disease and brain amyloidosis]. / Prionovye bolezni i amiloidoz golovnogo mozga.

Human prion disorders include Kuru, Creutzfeld-Jakob disease (CJD), Gerstman-Straussler-Scheinkler syndrome (GSS), fatal familial insomnia (FFI) and prion protein cerebral amyloid angiopathy (PrPCAA). Prion diseases manifest as infections, genetic and sporadic disorders. In these diseases an abnormal form of the host's protein, prion protein protease-resistant (PrPres), is essential for pathogenic process. Host protein, prion protein protease-sensitive (PrPsen) in humans is encoded by a single copy gene (PRNP) located in the short arm of chromosome 20. To date, 19 different mutations in PRNP have been found that cause inherited prion disease. In these diseases PrPsen undergoes conformational changes involving a shift from alpha-helix to beta-sheet structures. This conversion is important for PrP-amyloidogenesis which occurs to the highest degree in GSS, while it is less frequently seen in other prion diseases. Pathomorphologically, amyloidogenesis in the brain is characterized by formation of PrPres conglomerates, diffuse homogeneous deposits and pleomorphic fibrillar amyloid plaques. The neurotoxic activity of PrPres and its fragments supports the causal relationship between PrPres deposits and neuropathological events in prion diseases. Congo-red and certain sulfated glycans potently inhibit PrPres formation. This raises the potential of therapeutic strategies for the treatment of these diseases.

[Identification of components of the extracellular matrix in trophoblastic cell columns of human placenta]. / Vyiavlenie komponentov vnekletochnogo matriksa v tsitotrofoblasticheskikh stolbikakh platsenty cheloveka.

The distribution of five components of the extracellular matrix was studied in human placenta (9-12 and 39-40 weeks of gestation) by an indirect immunofluorescence method with polyclonal monospecific antibodies. In trophoblastic cell columns fibronectin, collagen types IV and V formed homogeneous deposits, whereas collagen types I and II comprised small conglomerates and scanty, discrete granules. The origin of these macromolecules was discussed.

Immunofluorescent localization of collagen types I, III, IV, V, fibronectin, laminin, entactin, and heparan sulphate proteoglycan in human immature placenta.

The distribution of eight components of the extracellular matrix in immature human placenta was studied by an indirect immunofluorescence method with monospecific antibodies. In the stroma of the term chorionic villi, collagen types I, III, IV, V, and fibronectin formed a mesh of fibers and conglomerates. Heparan sulphate proteoglycan formed multiple conglomerates, whereas laminin comprised small, scanty, discrete granules. Collagen type IV, laminin, entactin, and heparan sulphate proteoglycan were confined to the basement membrane of the trophoblast. Sometimes, only collagen type IV was identified in fetal vascular basement membrane.

Confocal and conventional immunofluorescent and immunogold electron microscopic localization of collagen types III and IV in human placenta.

Confocal and conventional indirect immunofluorescence and immunogold electron microscopic methods were applied to examine the distribution of extracellular matrix constituents (collagens types III and IV) in the villi of immature and term human placentae. The immunofluorescence study revealed that collagen type III is more distinct in the villous stroma of term placenta as compared with that of the first trimester. Collagen type IV was detected mainly in endothelial and epithelial basement membranes and interestingly also to a certain extent in the stroma. Results obtained using immunoelectron microscopy support the proposal that collagen types III and IV are characteristic of stromal and basement membranes, respectively. Stromal collagen type IV is apparently localized in association with the interstitial types of collagen (I and III), in the villous stroma of term placenta.

Immunohistochemical investigation of autoantibodies to nerve fibers in cardiomyopathy.

The immunofluorescence technique was used to trace auto-antibodies to neural structures in the blood serum of 180 patients with various cardiomyopathies and 20 healthy probands (controls). Incubation of cryostat slices of heart, kidney, spinal cord and medulla oblongata of Wistar-rats or of cell cultures of embryonal spinal cord with the blood serum of patients with cardiomyopathies resulted in immunofluorescence of nerve fibres and neuronal perikaryon. The controls were negative. The question remained unanswered for the nature of the involved antigen. Neurohistochemical findings suggested auto-antibodies in sera of patients to be orientated to cholinergic endings. The authors suggest the immunomorphological approach as practicable for revealing auto-antibodies in neurohistological studies.

[Distribution of myosin, desmin and vimentin in smooth muscle cells of human embryonic vessels]. / Raspredelenie miozina, desmina i vimentina v gladkomyshechnykh kletkakh émbrional'nykh sosudov cheloveka.

Immunofluorescent study of embryonal vessels of man using antibodies to myosin, desmin and vimentin showed heterogeneity of smooth muscle cells. It is supposed that the use of desmin as a marker of cell differentiation can increase the role of modified phenotypes in the development of the pathological process in the vascular wall.

[The viral and immunological characteristics of cardiomyopathies and myocarditis]. / Virusoimmunologicheskaia kharakteristika kardiomiopatii i miokarditov.

As many as 97 patients with myocardial lesions: congestive and hypertrophic cardiomyopathy (CMP), postmyocarditis CMP (PM CMP), myocarditis (MC), alcoholic heart injury (AHI), coronary heart disease (CHD), vegetodysovarian myocardiodystrophy were examined by means of a complex of the virological tests (for Coxsackie B, Epstein-Barr and hepatitis B viruses) and immunoassays (for antibodies to different components of the myocardium, leukocyte migration inhibition test, antibody-dependent cellular cytotoxicity test, measurements of T and B lymphocytes and their subpopulations, and so forth). Virus infection was shown to be of a role for the onset of acute MC (usually reversible) and congestive CMP. At the same time the autoimmune mechanisms of the lesions were conclusively ascertained in MC associated with heart failure and in PM CMP. In patients with congestive CMP and AHI coupled with heart failure, antibodies to nerve fibers of the myocardium could be demonstrated in the presence of T-lymphocyte deficiency and high titers of antibodies to Epstein-Barr virus. This does not allow excluding myocardial denervation leading to refractory heart failure. Some immunological parameters made use of in the study provide an opportunity of an objective evaluation of the effect glucocorticoid treatment produces on patients suffering from MC and PM CMP.

Participation of collagen types I, III, IV, V, and fibronectin in the formation of villi fibrosis in human term placenta.

The indirect immunofluorescence method was used to study the human term placenta in pathological pregnancy for the distribution of collagen types I, III, IV, V, and fibronectin in fibrosis stromatis villi. All collagen types and fibronectin were shown to participate in fibrosis villorum formation. Fibronectin was also detected in the fibrinoid that surrounded villi at stroma. The presence of free cytotrophoblast cells in the fibrinoid was accompanied by a noticeable increase in fibronectin fluorescence. A significant amount of collagen types IV and V and a less amount of collagen types I and III were identified.

[Immunofluorescence study of the extracellular matrix of the human placenta]. / Immunofluorestsentnoe izuchenie éktratselliuliarnogo matriksa platsenty cheloveka.

Distribution of collagen types I, III, IV, V and fibronectin in human placental villi has been studied by indirect immunofluorescence. During 9-12 weeks of pregnancy the extracellular matrix of villi represents a network of filaments organized in bundles and aggregates that contain collagen types I and III and finer filaments of collagen types IV and V. Collagen type IV is regularly detected in basal membrane of capillaries and particularly in villous epithelium, collagen type V and fibronectin are occasionally detected there. Marked immunofluorescent reaction on collagen types IV and V and fibronectin, and weak reaction on collagen type III is observed in cellular islets around cytotrophoblasts. In the fetus born in term placental villi have uniform immunofluorescence in thick basal membranes of fetal capillaries and of chorionic epithelium. The immunofluorescent reaction specific for all collagen types is uniform in villous stroma. Distribution of different collagen types and fibronectin, including the unusual localization of membrane collagen type IV, in villous stroma and cellular islets of early and mature placenta is discussed.

[Distribution of collagen types III and IV in human placental villi]. / Raspredelenie kollagena III i IV tipov v vorsinakh platsenty cheloveka.

Immunofluorescent examination showed more significant accumulation of interstitial collagen type III in the stroma of mature placenta compared with immature one. Localization of membrane collagen type IV was found neither in basal membranes of epithelium and villous vessels of mature term placenta, nor in their stroma. The described patterns of distribution of collagen types III and IV in human placenta villi were proved by immunoelectronmicroscopic method.

[The localization of the components of the extracellular matrix and cytoskeleton in myocardial biopsies in alcoholic cardiomyopathy]. / Lokalizatsiia nekotorykh komponentov vnekletochnogo matriksa i tsitoskeleta v miokarde bioptatov pri alkogol'noi kardiomiopatii.

Distribution of I, III, IV and V-type collagen, fibronectin, vimentin, filamin, and desmin in myocardial biopsy specimens of 8 patients with alcoholic cardiomyopathy was studied by indirect immunofluorescence. It is found that all types of collagen and fibronectin participate in formation of diffuse cardiosclerosis while small cardiosclerosis is formed by interstitial types of collagen and to a lower extent of fibronectin. Filamin and desmin distribution in cardiomyocytes proves deformation and destruction of Z-lines and intercalated discs.

[Characteristics of the extracellular matrix in the formation of sclerosis of the chorionic villi (immunofluorescence studies)]. / Osobennosti ékstratselliuliarnogo matriksa v formirovanii skleroza vorsin platsenty (immunofliuorestsentnoe issledovanie).

Distribution of the eight components of extracellular matrix in small villi of human placenta was studied with indirect immunofluorescence. Normal full-term pregnancy was found to present rough fibers and type I collagen conglomerates accumulated in the stromal center, while type III and V collagens occurred all over the villous surface. Stromal localization of type IV collagen was recorded as well as its presence in basal membranes of the epithelium and vessels. Fibronectin showed diffuse distribution concentrating along the vessels. Laminin, entactin and in lesser degree heparan sulphate proteoglycan were registered in epithelial and vascular basal membranes. Isolated sclerosis of the villi in pathological pregnancy involved stromal accumulation of type I, III collagens, small fragments of collagens type IV, V and fibronectin. Multiple sclerosis of adherent villi demonstrated hyalin-like conglomerates of various collagens and fibronectin filling up the stroma. Laminin, heparan sulphate proteoglycan and entactin were not observed at these sites.

[Epstein-Barr virus infection and congestive cardiomyopathy (serologic and immunomorphologic aspects)]. / Infektsiia virusom Epshteina-Barr i zastoinaia kardiomiopatiia (nekotorye serologicheskie i immunomorfologicheskie aspekty).

In serums of patients with congestive cardiomyopathy (CCM), patients with ischemic heart disease (IHD) and those of healthy subjects, presence of antibodies to capsid and early antigens of Epstein-Barr's virus (EBV) and to various structural components of myocardium was determined in order to study seroepidemiologic relations between the infection and CCM as well as immunopathogenic reactions against myocardium in this disease. Seroepidemiologic relation between EBV and CCM consisted in significant (compared to healthy subjects and patients with IHD) increase in average geometrical titres of antibodies to virus-associated antigens. Half of the patients with CCM had active EBV infection proved by presence of antibodies to early EBV antigen. Antibodies to various structural components of myocardium were found, including those to myocardial nervous fibers (for the first time) in 1/3 of the patients. Etiological role of active EBV infection in development of lymphomas during the post heart transplantation period in CCM as well as in myocardial nervous fibers damage in this disease is also discussed.

Monoclonal antibodies against chordin. Use in structural and immunohistochemical studies.

Eight MAbs have been developed against chordin and designated as At2-At9. It is shown that all antibodies are directed against identical, spatially overlapping or closely positioned epitopes of chordin. The chordin molecule has repetitive sites wherein epitopes for the eight MAbs are located. This site lies within a proteinase-resistant fragment of chordin, presumably a glycopeptide, of molecular mass between 2 and 10 kDa. Fluorescence staining of cryostat sections from stellate sturgeon with the use of At5 (indirect Coons' method) has revealed a positive reaction with notochord cells and sheath and with the spinal cord. No significant reaction with cartilage, muscle and kidney was detected.

Relative distribution of fibronectin and type I, III, IV, V collagens in normal and atherosclerotic intima of human arteries.

Spatial distribution of fibronectin and type I, III, IV and V collagen has been investigated in normal arterial intima, fatty streaks, and atherosclerotic plaques by indirect immunofluorescence on transverse sections. Two distinct types of extracellular matrix were revealed in atherosclerotic lesions. The fibrous plaques consisted mostly of interstitial collagen types I and III, contained moderate amounts of type V and none of type IV collagen or fibronectin. In the extracellular matrix of the fatty streaks and in some areas of the fibrous plaques containing large amounts of subendothelial cells, some interstitial collagen was revealed, an increased amount of type IV, some type V collagen and a lot of fibronectin. Similarities of the extracellular matrix in atherosclerotic lesions and granulation tissues are discussed.

[Pathohistology of costal cartilage and immunomorphologic characteristics of collagen in funnel chest]. / Patogistologiia rebernogo khriashcha i immunomorfologicheskaia kharakteristika kollagena pri voronkoobraznoi grudi.

Biopsy samples from the costal cartilage tissue were studied for 68 children with funnel deformity and from 20 children with normally formed chest. The authors present general morphologic features characteristic of the costal cartilage structure in norm and in case of funnel chest. These features include vast acellular sites, map-like areas, unmasked chondrin fibers and "marrow" cavities. In funnel chest they develop, however, 6-7 years earlier, than normally, and are consequent stages of the accelerated costal cartilage involution. Costal cartilage matrix was found to have an increased content of fibronectin and V collagen type in case of funnel chest. Besides III and IV procollagen types were noted in the chondrocytes. The accelerated growth of costal cartilages is involved in the formation of funnel chest.

Distribution of type I, III, IV and V collagen in normal and atherosclerotic human arterial wall: immunomorphological characteristics.

35 autopsies--aged 30 to 75 years--were investigated in order to establish trends of collagen localization in various types of arteries depending on age, arterial size and degree of atherosclerosis. Cryostat sections stained with highly specific antibodies to human types I, III, IV or V collagen, or with the antiserum to smooth muscle myosin were examined by the indirect immunofluorescence technique. Localization of type III collagen was very similar to that of type I. Fibrous structures of both type I and type III were then major constituents of the intima, media and adventitia. Sparse fibrils of type I and type III collagens were revealed in the subendothelium of unaffected intima. They gradually became abundant in the deeper intimal layers contrasting with loose fibrillar formations of the media. The content of interstitial collagens was significantly increased in the subendothelium of local intimal thickenings and in a thickened intima of the aged. This fact, considering the thrombogenicity of interstitial collagens, may be relevant to the atherogenesis through the "response-to-injury" mechanism. Type IV and type V collagens are localized to the endothelial basement membrane and basement membranes of smooth muscle cells of the intima and media. Diffusely distributed type V collagen was also observed in the intercellular space of the intima. In lipid streaks, parallel layers of condensed interstitial collagens separated groups of cells and extracellular lipid depositions. In fibrous plaques, types I and III became prevalent structural elements and their densely packed fibers occupied whole regions devoid of any type IV and type V collagen. Heavily thickened type IV collagen structures surrounding individual smooth muscle cells were found in fibrous plaques, but never, in unaffected intima.