[Chronic viral hepatitis--one of the most important problems of current medicine]. / Khronicheskii virusnyi gepatit--odna iz naibolee vazhnykh problem sovremennoi meditsiny.

Main aspects of the study of chronic virus infection now cover clinico-morphological characteristics, prognosis of chronic liver diseases (CLD) by HBV and HCV; characteristics of extrahepatic lesions produced by HBV and HCV; features of CLD of mixed etiology (viral and alcoholic); treatment of CLD of viral etiology. The hypothesis is suggested on the generalized character of HBV and HCV infection. Approach to the treatment of chronic viral hepatitis including extrahepatic manifestation is proposed.

[Morphological, cytogenetic and molecular biological characteristics of lung cancer in persons exposed for a long time to radionuclide radiation pollution in the Semipalatinsk region of Kazakhstan]. / Morfologicheskie, tsitogeneticheskie i molekuliarno-biologicheskie osobennosti raka legkogo, razvivshegosia u lits, dlitel'noe vremia prozhivavshikh na radioaktivno-zagriaznennykh territoriiakh Semipalatinskoi oblasti Kazakhstana.

Surgical and biopsy material was used from 57 patients with lung carcinoma (LC): 17 patients (group I) lived close to testing area from the childhood to 1993 and were exposed to radiation at the year dose 0.1 ber. For comparison surgical and biopsy material from 40 patients (group 2) was taken who lived in the territories of Kazakhstan (10 patients) and Moscow (30 patients) with normal radiation background. The following features of LC were found in the groups in question: constant observation of dust particles and interstitial and focal fibrosis in tumours of various localization and histological type; prevailing small cell carcinoma as compared to other histological types; high frequency of nonsmall cell lung carcinoma; higher expression of IGFII, IGFBP1,2 and rare expression of IGFB3; proliferative activity followed by an increased expression of c-myc, bcl-2.

[Role of chronic viral hepatitis in the development of hepatocellular carcinoma]. / Rol' khronicheskogo virusnogo gepatita v razvitii gepatotselliuliarnoi kartsinomy.

Role of HBV- and HCV-infections, liver cirrhosis, alcohol in the development of hepatocellular carcinoma, and hepatocyte dysplasia is considered.

[Combination of pulmonary lymphangioleiomyomatosis with skin leiomyomatosis and uterine leiomyoma]. / Sochetanie limfangioleiomiomatoza legkikh, leiomiomatoza kozhi i leiomiomy matki.

Clinical observation with morphological verification of the above combination in a 48-year-old patient is presented. Large cysts, dystelectasia, fibrosis and smooth muscle proliferation were found in the lungs. The characteristic feature of smooth muscle cells was their differentiation in the direction of myofibroblasts and expression of antigen interacting with HMB-45 antibodies as well as protein products involved in catecholamine metabolism and estrogen receptors.

[Chronic viral hepatitis and alcoholic liver: clinico-morphological correlations]. / Khronicheskii virusnyi gepatit i alkogol'naia pechen': kliniko- morfologicheskaia korreliatsiia.

69 patients with alcohol addiction infected with hepatitis viruses underwent clinical, laboratory and morphological examinations using light and electron microscopic studies of liver biopsies. Light microscopy revealed three variants of liver damage: viral, alcoholic and mixed. Both etiological factors affect manifestations and course of the disease as shown by electron microscopy in spite of morphological signs of only viral or mixed lesion. The lowest index of histological activity is found in combination alcohol + HCV, the highest index being in patients with HBV + HCV and HBV + HDV. Alcohol abuse in combination with HCV infection increases histological activity of liver damage.

[Carcinoids of lungs]. / Kartsinoidy legkikh.

The analysis of the results of the examination and treatment of 29 patients with carcinoids of the lungs has been carried out for 1984-1995. Peripheral carcinoids were detected in 59% of cases, of the tumor in the main and lobar bronchi was revealed in 41% of cases. The analysis showed that there are no symptoms, pathognomonic for carcinoids of the lungs; carcinoid syndrome was not detected in any patient. The examination (roentgenography and CT of the lungs, bronchoscopy) has not provided any objective, differential diagnostic criteria for carcinoids, cancer and benign tumors of the lungs. Morphological examination of the removed tumors allowed all the carcinoids to be divided in two types: typical (benign neuroendocrine tumor) and atypical (well differentiated neuroendocrine carcinoma). The final differentiation is possible only after conduction of thorough histological, electron microscopy and immunohistochemical examination. The principal method of carcinoids treatment is surgical one. The optimal surgical procedure is pneumonectomy or lobectomy with lymphadenectomy. Atypical resection of the lung without lymphadenectomy in peripheral location of the tumor is justified only in early stages of the disease and in cases of morphological verification of benign character of neuroendocrine tumor. Late results were followed up in 27 patients. In the group of patients with atypical carcinoids in terms of 6 to 12 months 3 patients died from progressing of the main disease. There were neither lethal outcomes nor signs of relapse of the disease in the group of patients with typical carcinoid. The terms of follow up were from 1 year to 12 years.

[Morphologic and molecular-genetic characterization of lung cancer developing in people who have worked at nuclear facilities and who have lived in Russian territories polluted after the accident at the Chernobyl power plant]. / Morfologicheskie i molekuliarno-geneticheskie osobennosti raka legkogo, razvivshegosia u lits, rabotavshikh na radiatsionnykh proizvodstvakh i prozhivavshikh na zagriaznennykh posle avarii na Chernobyl'skoi AES territoriiakh Rossii.

Clinicomorphological analysis of 15 lung carcinomas of patients who had been exposed for a long time to the radiation after the Chernobyl accident was performed. The material consisted of 10 surgical and 5 autopsy cases and was studied at the light, electron microscopic and immunohistochemical level. There were 6 peripheral, 8 central carcinomas and one massive tumor. Fibrous areas with many dust particles were found in peripheral carcinomas. In central tumors chronic obstructive bronchitis with epithelial dysplasia and metaplasia was observed. Carcinoma was represented by various histologic types: small cell (4 cases), combined small cell with squamous differentiation (5 cases), adenocarcinoma (5 cases), adenosquamous type (1 case). Peculiar calcium deposits in both stroma and parenchyma were found in tumors with glandular differentiation. Morphogenesis of calcium microdeposits may be connected with dust radioactive particles elimination. Central carcinoma had, in the majority of cases, a neuroendocrine differentiation and can be related to some types of small cell carcinoma. Peripheral cancer was mostly of a glandular differentiation and was, as a rule, carcinoma in the scar. Lung carcinomas studied had peculiar molecular-genetic features: lack or low bcl-2 expression, low Ki-67 expression and a high degree of c-myc expression. Tumors were characterized by a low apoptosis index independently of a histologic type. Apoptosis was not complete: lack of apoptotic bodies phagocytosis this resulting in postapoptotic detritus formation.

[Electron microscopic study of the liver in chronic viral hepatitis C complicated by alcoholic liver disease]. / Elektronno-mikroskopicheskoe issledovanie pecheni pri khronicheskom virusnom gepatite C v sochetanii s alkogol'noi bolezn'iu pecheni.

Combination of HCV-infection and alcoholic liver disease is associated with enhancement of hepatocellular damage (lipid and hydropic degeneration become diffuse), a decrease of hepatocyte necrotic foci and lymphomacrophagal infiltration, an increase of hepatocyte apoptosis and liver fibrosis, absence of lymphoid follicles. An important role in the genesis of these liver alterations is attributed to the combination of viral and alcoholic factors with persistence of hepatitis C virus and liver reticulo-endothelial system depression.

[Heterogeneity of pulmonary fibroblasts in tuberculosis]. / Geterogennost' legochnykh fibroblastov pri tuberkuleze.

Chronic inflammation and pneumofibrosis are the central events in tuberculosis morphogenesis. It was suggested that a certain type of fibroblasts may play a role in chronization of the inflammation and development of sclerosis in tuberculosis. Fibrous tissue from the foci of secondary tuberculosis (fibrous-cavernous tuberculosis and tuberculomas) of 35 patients were studied light- and electron-microscopically and immunohistochemically. (THY 1-)fibroblasts non-containing lipids and producing insulin-like growth factor 2 (ILGF 2), binding proteins 2 and 4 and epidermal growth factor receptors were found in the foci of secondary tuberculosis close to the granulomatous inflammation and in the new and scarrous fibrous connective tissue of the tuberculoma capsule and caverna walls. These fibroblasts are able for auto- and paracrine regulation of the proliferation of fibroblasts, epithelium and other cells in the inflammatory foci. (THY 1+) fibroblasts containing lipids were observed in the foci of old sclerotic changes among the rough collagen fibres. Thus, (THY 1-) fibroblasts probably play a key role in chronization of inflammation, proliferation and pretumorous dysplasia of pulmonary epithelium in secondary tuberculosis. (THY 1+) fibroblasts containing lipids may show more pronounced collagenesis and may persist under hypoxia condition in the collagenous scars for a long time.

[Comparative morphologic characteristics of viral hepatitis B and C]. / Sravnitel'naia morfologicheskaia kharakteristika virusnykh gepatitov B i C.

Using liver biopsies in chronic HBV and HCV infections and their combination, the authors found between them morphological difference represented by nonspecific morphological markers. The combination of fat and hydropic hepatocytes degeneration, their heterogeneity, lymphoid follicles of various location and maturation degree, sinusoidal cell hyperplasia, accumulation of lymphocytes and macrophages in sinusoids, destruction, proliferation and sclerosis of ductules are of a high significance in hepatitis C. Etiological markers of hepatitis B are so-called ground-glass hepatocytes and "sand" nuclei. Various combination of these markers are characteristic for HBV and HCV co-infections with predominance among them of a replicating virus.

[Ultrastructural studies of the detrusor in patients with benign prostatic hyperplasia]. / Ul'trastrukturnye issledovaniia detruzora u bol'nykh s dobrokachestvennoi giperplaziei predstatel'noi zhelezy.

Unstable bladder was diagnosed in 15.9% of patients with post-operative problems with urination. It is suggested that the mechanism of urination defects in patients with benign prostatic hyperplasia may imply not only mechanical compression, stretching of the posterior urethra, changes in the urethrovesical angle, but also detrusor abnormalities. Ultrastructure of bladder muscles was studied in 6 patients with benign prostatic hyperplasia. In all cases bladder tissue underwent dystrophic, hypertrophic or atrophic changes. Lesions of the contractile apparatus of the bladder were associated with microcirculatory vessels sclerosis. The above ultrastructural alterations should be considered in combined therapy of patients with benign prostatic hyperplasia.

[Nature of pseudo-amyloid masses in lymphocytic pneumonitis]. / Priroda psevdoamiloidnykh mass pri limfotsitarnom pnevmonite.

The material of open lung biopsies from a female patient with lymphocytic pneumonitis affecting mainly lower parts of the lungs was studied light- and electron-microscopically, immunohistochemically. Diffuse lymphoplasmacytic infiltration with an admixture of macrophages, single giant multinuclear cells and pseudo-amyloid inclusions were found. Morphogenesis of pseudo-amyloid inclusions is related to processes of pulmonary fibro-atelectasis with subsequent imbibition by immunoglobulins (hyperglobulinemia was found in circulating blood).

[Intercellular interactions in morphogenesis of initial lesions and sclerosis in interstitial lung diseases]. / Mezhkletochnye vzaimodeistviia v morfogeneze initsial'nykh povrezhdenii i skleroza pri interstitsial'nykh bolezniakh legkikh.

A total of 117 patients with pulmonary interstitial diseases (PID) were examined. The functional activity of alveolar macrophages was assayed in the lavage fluid and in lung tissue biopsy specimens from the generation of active oxygen forms, the secretion of tumor necrosis factor, fibronectin, expression of c-fos- and c-sis-oncoprotein. The stereotypic value for various PID was the development of alveolitis running in 2 stages: 1) early one, including exudative inflammation and 2) late one, involving sclerotic changes up to the formation of the honeycomb lung. This results in the block of the blood-air barrier and progression of respiratory failure and hypoxia in patients. The morphogenesis of fibrosing alveolitis is formed of alveolar septal damages caused by etiological agents of various nature, which is frequently unclear, by active forms of oxygen, lipid peroxidation products, proteases, tumor necrosis factor, which are produced by activated alveolar macrophages and polymorphonuclear leukocytes. The alveolar macrophage that secretes growth factors, c-fos- and c-sis-oncoproteins plays the key role in the progression of sclerotic changes. Lung cancer may develop at the end of fibrosing alveolitis at the stage of the honeycomb lung.

[Variants and stages in the course of idiopathic fibrosing alveolitis]. / Varianty i stadii techeniia idiopaticheskogo fibroziruiushchego al'veolita.

Clinicomorphological analysis covered 41 cases of idiopathic fibrosing alveolitis (IFA). The comparison of the degree of respiratory insufficiency, hypoxia, survival of the patients with cytogram of the bronchoalveolar lavage, morphological findings, generation of active oxygen forms by alveolar macrophages and leukocytes has provided evidence on an important role of alveolar macrophage in interstitial alveolitis and fibrosis in IFA. Three variants of chronic IFA are distinguished: aggressive, persistent and slowly progressive. The variants have different prognosis and need individual therapeutic approach.

[The clinico-morphological characteristics of interstitial lung diseases]. / Kliniko-morfologicheskaia kharakteristika interstitsial'nykh boleznei legkikh.

Electron microscopic and immunohistochemical methods were employed to study composition of collagens in extracellular matrix and quantify oncoproteins c-sis and c-fos. It was established that interstitial pulmonary diseases of various etiology are characterized at early stages by alveolitis with activation of alveolar macrophages, at late stages by interstitial fibrosis with accumulation of collagens type I, III, IV and V and epithelial dysplasia which is likely to initiate bronchioloalveolar cancer.

[Morphologic characteristics of nephrosclerosis: electron microscopic, immunohistochemical and histospectrophotometric study]. / Morfologicheskaia kharakteristika nefroskleroza: élektronno-mikroskopicheskoe, immunogistokhimicheskoe i histospektrofotometricheskoe issledovanie.

Combined study of nephrosclerosis revealed profound alterations of both extracellular matrix (ECM) and tubular epithelium. ECM alterations manifested in the accumulation in the stroma of I and III types of collagen, fibronectin, considerable increase of collagen IV and laminin.

[Nuclear oncoprotein expression in lung precancer and cancer at various stages of tumor progression studies at the level of light- and electron-immunohistochemistry]. / Ekspressiia iadernykh onkobelkov pri predrake i rake legkovo na raznykh stadiiakh opukholevoi progressii (po dannym svetovoi i élektronnoi immunohistokhimii).

68 cases of lung carcinoma, 3 carcinoids and 15 fibrosing alveolitis with foci of adenomatosis and bronchiolo-alveolar carcinoma were studied. Oncoproteins c-fos, c-jun, c-ets-1, c-myc L and L-myc were identified in the tumour and surrounding tissue. Expression of c-fos was revealed in 79 of 138(59.4%) of proliferative and dysplastic changes of lung epithelium; c-jun in 40 of 61 (65.6%), c-ets-1 in 22 of 41 (53.7%), c-myc in 41 of 96(42.7%) and L-myc in 15 of 61 (24.6%), mainly in altered bronchial epithelium with a positive reaction to the antibodies against neuron specific enolase and S100 protein. More pronounced expression of nuclear oncoproteins, heterogeneity of their location in tissues, frequent cytoplasmic location in tumour cells were typical for lung carcinoma.

[Intrauterine mycoplasmosis combined with bilateral adrenal ganglioneuroblastoma]. / Vnutriutrobnyi mikoplazmoz v sochetanii s dvustoronnei ganglioneiroblastomoi nadpochechnikov.

The paper reports lethal intrauterine mycoplasmosis in a newborn girl. Her mother suffered from genital mycoplasmosis and had blood antibodies to Myc. Hominis and Ureapl. urealyticum. Most pronounced changes are found in the liver: hepatocyte degeneration and necrosis with PAS- and azur-positive granules in the cytoplasm of hepatocytes and macrophages, lymphohistiocytic infiltration of portal tracts and parenchyma, biliary duct proliferation, cholestases. The lungs: interstitial pneumonia with minimal alteration of the bronchial epithelium. The above spectrum of alterations suggests transplacental contamination. Ganglioneuroblastoma consisting of embryonal neuroblasts found in the adrenals is considered as an independent disease. The first child of this woman died 14-days old and had morphological signs of the intrauterine infection and pronounced liver dysplasia; possible oncogenicity of mycoplasma is discussed.

[Expression and co-expression of cellular oncogenes in the course of tumor progression in neuroendocrine lung tumors]. / Ekspressiia i koékspressiia kletochnykh onkogenov v khode opukholevoi progressii v neiroéndokrinnykh opukholiiakh legkikh.

The tumours studied were as follows: benign carcinoids, well differentiated carcinomas (atypical carcinoids) and poorly differentiated tumours (small-cell carcinoma with neuroendocrine differentiation). Oncoproteins c-myc, c-fos, c-jun, L-myc, c-sis, c-ras, c-src, c-ets-1, c-met were studied immunohistochemically in the material obtained from 25 patients during the operations. A higher expression of c-fos, c-jun, c-ets-1 and c-met is observed at early stages of progression and that of c-myc and L-myc at later stages. Enhancement of c-myc and L-myc expression correlated with the invasiveness and lymphogenic metastasizing. Co-expression and negative correlation between some oncogenes are established. The data obtained may be used for prognosis and therapy.