[Dilated cardiomyopathy as clinical syndrome: experience with nosological diagnostics with biopsy and treatment approaches].

AIM: To study possibility of nosological diagnosis in patients with dilated cardiomyopathy (DCMP) with use of myocardial biopsy. MATERIAL AND METHODS: The trial enrolled 62 patients (23 females) with DCMP syndrome (end diastolic left ventricular size > 5.5 cm, ejection fraction < 55%). Mean age of the patients was 46.0 +/- 12.8 years. The examination included diagnosis of viral infections (Herpes virus, parvovirus B19), measurement of anticardial antibodies titer, 99Tc-MIBI single photon emission computed tomography of the myocardium, multislice computed tomography, MRT of the heart, coronarography, morphological study of the myocardium (n=20) with application of polymerase chain reaction (PCR) for H.simplex viruses of types 1, 2 and 6, herpes zoster, Epstein-Barr, cytomegalovirus, parvovirus B-19, adenoviruses. The control group (20 operated patients with valvular heart disease and coronary heart disease) was examined for viral genome in the blood and myocardium. RESULTS: Complex examination of DCMP patients showed the following distribution by nosological entuities: myocarditis (n=41, 66.1%) including virus-positive (n=14), primary DCMP (n=16, 25.9%) including with non-compact myocarditis (NCM) in 3, with debute at delivery of the child--in 3. Arrhythmogenic right ventricular dysplasia combined with viral myocarditis (n=2), genetic myopathy (n=1) and Takayasu disease (n=1) combined with NCM, isolated NCM (n=1) were diagnosed in the rest cases. Morphological investigation of the myocardium was made in 20 patients: diagnosis of myocarditis and primary DCMP were made in 70% (including in 2 patients with CHD) and 20%. Detection of viral genome was 20 and 15% in the study and control group, respectively, in the myocardium--in 57.9 (test for parvovirus B19 was not made in 26%) and 65.0% (complete diagnosis). All the virus-positive patients with DCMP were diagnosed to have signs of active/borderline myocarditis. Diagnostic criteria and poor prognosis factors were defined. CONCLUSION: The nosological diagnosis of DCMP was made in all the examinees basing on the complex of clinical, case history and device evidence. The diagnosis was morphologically verified in 33.9% patients. Treatment approaches are developed.

[An immunomorphological study of the effect of ionizing radiation on the nonlymphoid structures of the mouse thymus using monoclonal antibodies]. / Immunomorfologicheskoe izuchenie vliianiia ioniziruiushchei radiatsii na nelimfoidnye struktury timusa myshei s pomoshch'iu monoklonal'nykh antitel.

Expression of cytoskeleton components revealed with monoclonal antibodies was increased in epithelial cells of mouse thymus one day after total gamma-irradiation with doses of 0.5-4.0 Gy, while after the doses of 10 and 15 Gy it was decreased. The antigen expression was reversed to initial level 14 days after the dose of 4 Gy; thymocyte depletion was progressed and continuous massifs of epithelial cells was formed. The oval cysts and immunoglobulin deposits were appeared in thymus two months after irradiation with the dose of 4 Gy.

[Use of a combined epidemiological, virological and morphological analysis of rubella infection for an epidemiological survey of congenital rubella]. / Primenenie kompleksnogo épidemiologicheskogo i virusologo-morfologicheskogo analiza krasnushknoi infektsii v tseliakh épidemiologicheskogo nadzora za vrozhdennoi krasnukhoi.

The results of composite epidemiological, virological and morphological studies of intrauterine rubella infection performed in 1979, in the period of maximum increase of rubella incidence in Moscow for 11 years (1969-1979) are presented. Investigations of 125 foci of rubella established a relatively high frequency of contacts of pregnant women with the source of infection in families of rubella patients. Twenty-nine cases of clinically manifest and inapparent rubella among pregnant women were detected and confirmed in the laboratory; intrauterine infection at 3-17 weeks was established in 16 out of 18 virologically examined women. The ratio of the disease forms was 3.5 : 1. Using laboratory methods of investigations, rubella of pregnant women was confirmed in 100% cases. From the aborted and fetal materials collected in the disease or inapparent infections of pregnant women rubella virus was isolated in 88.9%, marked pathomorphological lesions were found in organs of 61% of the fetuses examined. The organotropism of rubella virus was confirmed by a high rate (87%) of virus isolation from placenta and umbilical cords as well as by localization of morphological lesions in these organs and in the eye lens tissues. These characteristics of marked teratogenic potentials of the circulating virus strains indicate the necessity of organization of regular epidemiological surveys of rubella in pregnant women for prevention of congenital rubella in the USSR.

[Venous immunomorphology in acute experimental thrombosis and human recurrent migrating thrombophlebitis]. / Immunomorfologiia ven pri éksperimental'nom ostrom tromboze i pri retsidiviruiushchem migriruiushcem tromboflebite cheloveka.

The direct immunofluorescence procedure was used to demonstrate immune complexes (fixed immunoglobulins) in the internal and external sheath of veins of a dog with experimental acute thrombosis caused by partial ligation of the ileofemoral vein in the presence of immunization of the animal with extracts of auto- and homologous vein tissue. The results suggest the participation of auto-immune processes in the pathogenesis of acute thrombosis of the main veins.

[Immunofluorescence study of reactions between the serum of patients with rheumatoid arthritis and components of connective tissue cellular elements]. / Izuchenie reaktsii syvorotki bol'nykh revmatoidnym artritom s komponentami kletochnykh élementov soedinitel'noi tkani metodom immunofliuorestsentsii.

By means of immunofluorescence using sera against three classes of human immunoglobulins (IgG, IgM, IgA), localization of the components (or one of the components) responsible for reaction of sera from patients with rheumatoid arthritis (RA) with connective tissue antigens was found to be in the cytoplasm of different kinds of cell elements of the connective tissue present in joints. Sera from RA patients collected at different stages of the disease reacted with connective tissue cell elements in titers of 1 : 64 to 1 : 1024, whereas sera from normal subjects (in 33% of specimens) reacted only to 1 : 8--1 : 16.

[The immunopathological mechanisms of the skin lesion in erysipelas patients]. / Immunopatologicheskie mekhanizmy porazheniia kozhi u bol'nykh rozhei.

The localization of bound IgG, IgA, IgM and component C3 of the complement in the focus of skin lesion in patients with different forms of erysipelas has been studied by the method of direct immunofluorescence. The presence of fixed immune complexes and component C3 in the affected areas of the skin at the acute period of the disease and their absence in the healthy areas of the skin have been established, which seems to be indicative of the presence of the local immunocomplex process in erysipelas. This process is one of the mechanisms of erysipelatous inflammation.

[Immunomorphological (light and electron microscopic) diagnosis of human squamous cell cancer using monoclonal antibodies]. / Immunomorfologicheskaia (sveto- i élektronno-mikroskopicheskaia) diagnostika ploskokletochnogo raka cheloveka s pomoshch'iu monoklonal'ny kh antitel.

It is shown with fluorescent and peroxidase labels for antibodies that the antigen to which the monoclonal antibody A-6/2 is directed, is a marker for cells of the basal stratified epithelium (basal-cell antigen). This antigen persists in squamous cell carcinomas of various sites and degrees of differentiation, but does not occur in tumors of other origins. With electron immunocytochemistry, the antigen was found to be located in tonofilaments and desmosomes of human squamous cell carcinoma. The A-6/2 monoclonal and basal-cell antigen may be used when developing immunomorphologic (light- or electronmicroscopic) procedures for histogenetic diagnosis of these carcinomas.

[Cardiomyocyte cytoskeleton in dilated cardiomyopathy and ischemic heart disease]. / Ul'trastruktura mezhmitokhondrial'nykh kontaktov kardiomiotsitov cheloveka pri alkogol'noi kardiomiopatii i ischemicheskoi bolezni serdtsa.

Summary. Vinculin, the protein of cardiomyocyte cytoskeleton in the myocardium of patients with a dilated cardiomyopathy and ischemic heart disease, was revealed by means of monoclonal antibodies and by a method of indirect immunofluorescence. Cytoskeleton of patients with dilated cardiomyopathy is disorganized, hypertrophic and contains greater amounts of vinculin than cytoskeleton of normal cardiomyocytes. This most likely negatively influences cell contractile capacity. The vinculin content was also higher in cardiomyocyte cytoskeleton of patients with ischemic heart disease but at a less degree than in patients with dilated cardiomyopathy.

[Local shwartzman phenomenon in animals with a complete absence and a reduction of the normal microflora]. / Mestnyi fenomen Shvartsmana u zhivotnykh pri polnom otsutstvii i reaktsii normal'noi mikroflory

Macro- and microscopic changes were studied in case of reproduction of the local Schwartzmann phenomenon in animals with various extent of bioisolation. It was revealed that the Schwartzmann phenomenon was positive in the usual animals and negative in the germ-free guinea pigs and in the animals with reduced enteric microbial flora given sterile diet. In the absence of microscopic changes in the germ-free animals there was revealed in their skin a neutrophilic-mononuclear infiltration of the derma, dilatation of the vessels, thrombosis of individual vessels. Apart from the same changes in guinea pigs with a reduced microbial flora, there were found focal extravasation and thrombosis of a somewhat greater number of vessels. There was no marked thromboses of small branches of the vessels, extensive hemorrhages or necroses which usually accompanied positive Schwartzmann phenomenon.

[Basal cell cross-reacting antigen in normal and neoplastic human tissues]. / Bazal'nokletochnyi perekrestno reagiruiushchii antigen v normal'nykh i opukholevykh tkaniakh cheloveka.

The method of immunofluorescence was used to study location of the basal cell cross-reacting antigen shared by group A streptococcus, and multilayer epithelium of the mucous membrane of the oral cavity, oesophagus, vagina, cervix, urinary bladder, eye conjunctiva, epithelial cells of the mammary and salivary gland ducts of man. The cross-reacting antigen possessing tissue specificity was found in human tumor cells histogenetically associated with the tissues carrying the antigen (basal cell carcinoma, squamous cell carcinoma of the skin, larynx, cervix) but not in the cells of tumors of different genesis (infiltrative mammary gland carcinoma, adenocarcinomas of the stomach and intestines). The results obtained will serve as the basis for the development of an immunological method for differential diagnosis of poorly-differentiated human tumors and for some problems of histogenesis of neoplasias.

[A case of seronegative systemic lupus erythematosus (an immunopathological study)]. / Sluchai seronegativnoi sistemnoi krasnoi volchanki (immunopatologicheskoe issledovanie).

A case of systemic lupus erythematosus (SLE) in a 37-year-old female is described which was primarily diagnosed as epilepsy. Immunopathologically, an immunoglobulin in the nuclei of the majority of cells in the skin biopsy and blood cells was found against the background of the lack of SLE manifestations (antinuclear factor in the circulating blood, skin lesions, etc.). Antibodies against the antigen of vascular intima are revealed in the blood by means of the indirect immunofluorescence. The epilepsy diagnosis was established due to the prevalence of the brain vessels affection (frequent loss of consciousness). The progression of the disease with the involvement of joints, heart, lungs and other organs, high indexes of the rheumatoid factor made it necessary to differentiate between rheumatoid arthritis and SLE. The immunopathological examination confirmed the SLE diagnosis. Hemosorption combined with a standard therapy was followed by the decrease of the immunopathological manifestations.

[Immunopathologic study of the myocardium in dilated cardiomyopathy]. / Immunopatologicheskoe issledovanie miokarda pri diliatatsionnoi kardiomiopatii.

Myocardial tissues of patients with dilated cardiomyopathy were studied by immunofluorescence. While immunoglobulin A fixation was observed in myocardial capillary wall and cardiomyocyte sarcolemma in the majority of patients (11 of 12), immunoglobulin G and C3 complement component were a rare finding. In the vessel wall of heart allografts immunoglobulin A fixation occurred 3-6 days after transplantation. As a result of the intensive immunosuppressive therapy which was used after the operation immunoglobulin A disappeared from heart allografts within 4-5 weeks. Immunoglobulin A fixation in the heart of patients with dilated cardiomyopathy is attributed to the anti-tissue or antivirus antibodies and probably is involved in the development of this disease.

[Humoral immunopathologic changes in the myocardium after clinical allotransplantation of the heart]. / Gumoral'nye immunopatologicheskie izmeneniia v miokarde pri allotransplantatsii serdtsa v klinike.

Endomyocardial diagnostic biopsies, recipient heart removed at operation, endomyocardial biopsies of allotransplants and postmortem material were studied using immunofluorescence to specify immunopathological process and to detect humoral rejection. Altogether 306 samples from 55 patients were studied. In the early postoperative period (one year) 8 out of 18 patients with heart transplants repeatedly showed immunopathologic picture of acute humoral (vascular) rejection which was characterized by a widespread immunoglobulin G and complement fixation in the capillary walls accompanied by enhanced capillary permeability and fibrin deposition in intestitial tissue. Such patients often had graft dysfunction. 1 to 5 years after transplantation in 24 out of 37 patients discrete focal immunoglobulin and complement fixation was observed as one of chronic rejection component.

[Cross-reacting epithelial antigen of ectodermal origin in mouse tumors]. / Perekrestnoreagiruiushchii antigen épiteliia éktodermal'nogo proiskhozhdeniia v opukholiakh myshei.

Cross-reacting antigen (CR-antigen) previously found by indirect immunofluorescence in cell elements of murine multilayer epithelial cells (except corneal epithelium) to play the role of antigenic label of cover epithelia of ectodermal origin was found in mice tumor cells, related histogenetically with multilayer epithelium (transplantable proventricular cancer, two strains of squamous-cell cervical cancer in mice). CR-antigen was observed in transplantable breast adenocarcinoma and in transplantable mice teratocarcinoma.

[Ultraimmunocytochemical diagnosis of squamous cell cancer of the digestive tract]. / Ul'traimmunotsitokhimicheskaia diagnostika ploskokletochnogo raka pishchevaritel'nogo trakta.

Procedure using fluorescent and peroxidase labeling and monoclonal antibodies to basal-cell antigen of multilayer epithelium showed the antigen to occur in squamous cell cancer irrespective of site and degree of cell differentiation; this, however, was not the case with tumors of other origins. Ultraimmunocytochemical method was used to identify localization of the antigen at cellular and subcellular levels, namely, in tonofilaments and desmosomes. Said situation is considered to suggest squamous cell carcinoma.

[Production of monoclonal antibodies to tissue-specific antigens of human skin epithelium]. / Poluchenie monoklonal'nykh antitel k tkanespetsificheskim antigenam épiteliia kozhi cheloveka.

Immunization of BALB/c mice with non-type-specific protein antigens of the cellular wall of group A streptococcus and formalin-treated streptococcal culture resulted in stimulating production of polyclonal autoantibodies to antigens of the epithelium of human and murine skin. As a result of hybridoma technique using splenic cells of immunized animals, monoclonal antibodies to different antigens of epidermal cell cytoplasm, i.e. antigen of basal cells, antigen of differentiated cell layers (spinous and granular) and antigen common to cells of all epidermal layers, were obtained. The immunofluorescence tests on monoclonal antibodies to epidermal basal cell antigen showed them to engage cells only of tumors histogenetically associated with the epidermal tegumental epithelium.

[Effect of hemosorption on the dynamics of immunopathologic changes in the skin of patients with diseases accompanying the immune complex syndrome]. / Vliianie gemosorpbtsi na dinamiku immunopatologicheskkh izmenenii v kozhe bol'nykh s zabolevaniiami, soprovozhdaiushchimisia sindromom immunnykh kompleksov.

In the majority of diseases with the immune complexes (IC) syndrome, elimination of IC from the body is markedly disturbed. The authors carried out a study with the aid of the direct immunofluorsecence technique. The use of hemosorption in the treatment of patients with grave patterns of systemic lupus erythematosus, rheumatoid arthritis, psoriasis, systemic vasculitis and similar illnesses in conjunction with conventional therapy (corticosteroids, cytostatics) leads to sequestration of the depositions of immune complexes from the skin. As early as after the first hemosorption one can observe the displacement of IC from the derma to the epidermis, advance of IC towards the stratum corneum. After the third session in hemosorption IC granules appear on the body surface, in the form of warty formulations which are removed afterwards together with skin scales. It is assumed that hemosorption recovers the secretory function of the skin, aimed at IC elimination.

[Cross-reacting antigen common to stratified squamous epithelium and Streptococcus group A in tumors of epidermal origin]. / Perekrestno reagiruiushchii antigen, obshchii dlia mnogosloinogo ploskogo épiteliia i streptokokka gruppy A, v opukholiakh épidermal'nogo proiskhozhdeniia.

A tissue-specific basal-cell antigen of stratified squamous epithelium which enters into cross reaction with group A streptococcus polysaccharide was detected in the cytoplasm of human basal- and squamous-cell tumor cells which are associated histogenetically with skin epithelium. However, it was not found in the cells of entodermal tumors (stomach and intestinal adenocarcinoma). Considering earlier reports on the detection of cross reacting antigen in experimental ectodermal tumors, these results suggest the development of an additional histogenetical method of differential diagnosis of human tumors which arise in ectodermal tegumental epithelium.

[Antibodies induced by group A Streptococcus reacting with epidermis elements in patients with basalomas]. / Antitela, indutsiruemye streptokokkom gruppy A, reagiruiushchie s komponentami épidermisa bol'nykh bazaliomoi.

Microbial mass of cultured streptococci treated with pepsin as an immunosorbent was used for isolation of an immunoglobulin factor which specifically reacted with elements of basal membrane of epidermis of basal cell cancer patients in an immunofluorescence test. The reaction took place in skin bioptates obtained both from the zone of tumor growth and distant regions. Antigens isolated from the basal membrane of skin epithelium of healthy subjects did not react with immunoglobulin factor.

[A method of detecting soluble immune complexes in tissue biopsies]. / Sposob vyiavleniia rastvorimykh immunnykh kompleksov v bioptatakh tkanei.

Pretreatment of cryostat slices of tissue biopsy specimens with 30-50% water ethanol mixture increases the rate of detection of immune complexes in the intercellular substance of the epidermis to 100% in patients with acantholytic pemphigus. This method permitted the detection of immune complexes in all the examined cases with benign familial Hailey-Hailey pemphigus, which has never been reported heretofore. The authors believe that 30-50% water-ethanol mixture is capable of soft denaturation of proteins, stabilizes the slightly affine antibody-antigen relations, and aggregates soluble immune complexes into larger protein formations, this preventing their washing out from tissues.