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Biomedical subjects

Y Kapanci

Publications and source records attributed to Y Kapanci.

At least 19 recordsLinked to original sources

Hepatitis B virus, alpha-fetoprotein synthesis, and hepatocellular carcinoma in Zaire.

We investigated the epidemiology of hepatocellular carcinoma (HCC) in Zaire, and evaluated the association between exposure to hepatitis B virus (HBV) and the development of HCC. Two hundred and twenty-three consecutive cases of HCC diagnosed over 19 years (1966-1985) were reviewed. HCC represented 8.32% of all carcinomas and 5.56% of all cancers. Frequency was higher in males (75.7%) than in females (24.3%); a sex ratio of 3/1. The majority (82.1%) of patients were aged 14 to 55 years with a peak occurrence in the fourth decade (28.6%). The mean age in males (41.27 +/- 17.5 years) and females (37.40 +/- 15.16 years) was significantly different (p < 0.02). Sera from 40 patients and 68 age and sex-matched controls were analyzed for markers of HBV infection: patients and controls had comparable rates of exposure (96% vs 72.1%, respectively). However, patients had significantly higher HBsAg carrier rates (56.7% vs 7.35%; p < 0.001), and lower anti-HBsAg seroconversion rates (25% vs 63.2%, p < 0.05). Using immunohistochemical analysis, the livers of patients were evaluated for HBsAg and HBcAg. These HBV antigens were more frequent in non-tumourous hepatocytes (53.3% vs 23.3%, respectively) than in HCC cells (13.3% vs 3.3%). Serum alpha-fetoprotein (AFP) was abnormal (> 20 ng/ml) in 90% of patients. The geometric mean (GM) AFP was 7273.8 ng/ml. AFP levels were significantly higher in HBsAg-positive HCC cases (GM: 19,322.6 ng/ml; 95% confidence interval (CI): [3639.2, 102,565.2]) than in antigen negative cases (GM: 1939.5 ng/ml; 95% CI: [182.8, 19,952.6]), but did not correlate with HBV replication. Immunohistochemical detection of AFP revealed a similar correlation between AFP and HBsAg. Neither AFP level nor HBsAg production correlated with cellular atypia or tumor grade.

Adolescent

Cytoskeletal features of alveolar myofibroblasts and pericytes in normal human and rat lung.

Frozen or paraffin-embedded human and rat lung specimens were stained with antibodies against total actin, alpha-smooth muscle (SM) actin, vimentin, desmin, or gelsolin. Alveolar interstitial myofibroblasts [i.e., contractile interstitial cells (CIC)] were labeled by total actin antibody but not by alpha-SM actin antibody. They stained for vimentin and gelsolin and, in rat lungs, most of them for desmin. Pericytes located around venules at the junction of three alveolar septa were always positive for alpha-SM actin and never for desmin. Tissue samples were also immunostained by an alpha-SM actin antibody and studied by electron microscopy. With this technique we confirmed that cells, identified as pericytes on the basis of their location, were intensely labeled by alpha-SM actin antibodies, whereas alveolar myofibroblasts were not. We conclude that in the lung interstitium pericytes and alveolar myofibroblasts have distinct cytoskeletal features, alpha-SM actin antibody staining being a simple method to distinguish between them. Furthermore, it appears that alveolar myofibroblasts have a peculiar pattern of cytoskeletal protein composition which, in the rat, is similar to that previously described for stromal cells in uterine submucosa, liver sinusoids (Ito cells), or the core of intestinal villi.

Actins

[Primary malignant non-Hodgkin lymphomas of the digestive tract: the role of surgery].

Forty-two patients with non-Hodgkin's malignant lymphoma (NHML) of the gastrointestinal tract were operated on between 1971 and 1989. NHML was located in the stomach in 23 (55%), in the small bowel in 16 (38%), and in the colon in 3 (7%). One-fourth of patients were hospitalized with an acute abdomen and had to undergo emergency surgery. Preoperative diagnosis was obtained in 40% of cases only. Since 1986, however, and thanks to immunohistochemistry, gastroscopy was able to diagnose gastric NHML in 10 of 11 cases. Twenty-six patients (62%) underwent curative surgery. Operative mortality was 11.9%, 42% in case of emergency surgery, but mortality was nil after elective procedures. Half the patients had no further treatment. Five-year survival was 67%. Except for the mucosa associated lymphoid tissue (MALT) tumors, histopathological characteristics had less influence on prognosis than expected. On the other hand, prognosis was significantly better after curative surgery (p less than 0.001).

Female

Histopathologic features of hepatocellular carcinoma in Zaire.

The pathology of hepatocellular carcinoma (HCC) was studied based on 223 Zairian HCC cases registered from 1966 to 1985. The observations included the following: (1) hepatitis B surface antigen (HBsAg) status, (2) histologic types, (3) degree of cellular differentiation, and (4) frequency and types of the accompanying cirrhosis. Serum HBsAg was positive in 56.7% of HCC patients and 5.7% of controls (P less than 0.001). Immunohistochemical localization of HBsAg was positive in 53.3% in normal hepatocytes and in 10% in neoplastic cells. Morphologically, mixed type HCC (48.4%), trabecular (31.4%), and compact variants (13.5%) were predominant. Clear cell and pseudoglandular variants were rare (less than 1%). The majority of tumors (83%) were poorly differentiated HCC (Grades: 2-3, 3, 3-4, and 4). Well-differentiated HCC were extremely rare (0.5%). Fifty percent of HCC arose in a cirrhotic liver, predominantly of the macronodular (67.4%) inactive (55%) type. The micronodular cirrhosis was very uncommon (1.1%). These findings clearly show the excess of poorly differentiated HCC in African patients and suggest a possible link between the morphologic features of HCC in Africa and its extraordinary fast-running course.

Adolescent

Modulation of actin isoform expression in alveolar myofibroblasts (contractile interstitial cells) during pulmonary hypertension.

Lungs of 37 patients with pulmonary hypertension (PHT), 5 normal human lungs, and 30 normal rat lungs, were studied using immunohistochemical stainings for actin, alpha-smooth muscle (alpha-SM) actin and desmin. The type of PHT was determined on clinicopathologic grounds (in 17 cases by catheterism); 20 patients had precapillary and 17 postcapillary PHT. In normal lungs, myofibroblasts, ie, contractile interstitial cells (CIC), distributed in alveolar septa, were not stained by alpha-SM actin antibodies. Only around the venules, were cells labeled by this antibody present. Furthermore, there were bundles of alpha-SM actin-positive cells around the openings of air sacculi into the alveolar ducts. In precapillary PHT, the distribution and immunostaining properties of interstitial cells remained unchanged; alpha-SM actin-positive cells were observed in thickened arterial intima and in plexiform lesions. In postcapillary PHT secondary to heart failure, to mitral stenosis, or in veno-occlusive disease, many interstitial cells in the alveolar septa were decorated by alpha-SM actin antibodies but not with desmin. The authors propose that, in postcapillary PHT, mechanical stretch due to capillary congestion may be responsible for the generation of cells that express an actin isoform associated with smooth muscle.

Actins

Tumor necrosis factor/cachectin plays a key role in bleomycin-induced pneumopathy and fibrosis.

The role of TNF-alpha/cachectin in the pneumopathy elicited by bleomycin has been investigated. After a single intratracheal bleomycin instillation, an increase of the lung TNF-alpha mRNA level was evident, from days 5 to 15, as shown by Northern gel analysis of whole lung RNA. In contrast, lung IL-1-alpha and GM-CSF mRNA were not detectable. In mice passively immunized with rabbit anti-mouse TNF-alpha IgG, the bleomycin-induced collagen deposition, evaluated by the total lung hydroxyproline assay on day 15, was prevented. Depletion of the CD4 and CD8 T lymphocytes by an in vivo treatment with mAb prevented the bleomycin-induced increase of TNF mRNA level and fibrosis. After an administration of bleomycin in continuous intraperitoneal perfusion, the diffuse alveolar damage observed by light and electron microscopy was almost completely prevented by anti-TNF antibody. These results indicate that in response to bleomycin, the T lymphocytes induce, by an undefined mechanism, an increase of the pulmonary TNF production, which leads to alveolar damage, growth of fibroblast, and collagen deposition.

Animals

A case of Encephalitozoon cuniculi peritonitis in a patient with AIDS.

A 45-year-old man with acquired immune deficiency syndrome (AIDS) presented with an unusual peritonitis resulting from a microsporidian infection. An inflammatory mass formed by the omentum magnum was revealed at partial autopsy. This mass was infested with parasites measuring 2.5-2.6 microns by 1.2-1.5 microns, which appeared gram positive and stained dark blue with Giemsa stain. These organisms were pale pink with Kinyoun stain, and occasionally one of their poles was periodic acid-Schiff positive. Sporoblasts and spores contained in parasitophorous vacuoles were revealed by electron microscopic examination. These spores were mononucleated, without mitochondria, and had a polar filament with four or five coils. They were identified as Encephalitozoon cuniculi. Peritonitis resulting from this parasite has not been reported previously, however, it should be suspected among rare infections resulting from unusual parasites in patients with AIDS.

Acquired Immunodeficiency Syndrome

Pneumopathies of the graft-versus-host reaction. Alveolitis associated with an increased level of tumor necrosis factor mRNA and chronic interstitial pneumonitis.

Irradiated (CBA x B10)F1 hybrid mice were injected with parental T lymphocyte-depleted bone marrow cells, (BMC), or with parental BMC together with T lymphocytes in an amount inducing greater than 80% mortality by day 40. Recipients of T cell depleted BMC did not show any mortality or significant pulmonary alterations, whereas recipients of BMC with T lymphocytes showed an alveolitis during the acute phase of the graft-versus-host reaction (GVHR) (day 15 to 25), characterized by: (a) alveolar hemorrhages, (b) increase of the number of alveolar leukocytes, (c) platelet microthrombi, (d) damage of the alveolar endothelial and epithelial cells, (e) increase of the turnover rate of the alveolar cells as shown by 3HTdR labelling, (f) increase in cell number and protein content of the bronchoalveolar lavage. These lesions were severe in the B10 versus F1, but absent in the reciprocal CBA versus F1 GVHR combination. The alveolitis was associated with a marked increase in the level of tumor necrosis factor-alpha mRNA, as shown by Northern gel analysis of lung RNA and was partially prevented by passive immunization with a rabbit anti-mouse tumor necrosis factor-alpha antibody. Mice examined after 25 days of evolution (i.e., chronic GVHR) presented an interstitial pneumonitis characterized by the accumulation of mononucleated cells, resembling large granular lymphocytes, which infiltrated first the intima of the blood vessels, and subsequently the interstice and the bronchi. These data demonstrate that the GVHR alone (in the absence of chemotherapy or overt infection) can induce two types of pneumopathies, an alveolitis and an interstitial pneumonitis.

Animals

[Infectious pneumopathies in immunodepressed patients. Value of the study of bronchoalveolar lavage fluid].

During a period of 16 months 26 fluid specimens obtained by broncho-alveolar lavage (BAL) in 24 immunocompromised patients were examined. This material included 13 HIV positive patients and 11 patients presenting malignant hemopathies (MH), of whom 7 had had a blood marrow transplantation. The BAL fluid was divided into two equal parts, one of which was sent to the Institute of Pathology and the other to the Laboratory of Bacteriology of Geneva University Hospital. In some cases a transbronchial biopsy was also studied. Eight out of 13 HIV positive patients presented a Pneumocystis carinii infection and one a cytomegalovirus (CMV) infection (associated with atypical mycobacteria infection). In another case streptococcal pneumonia was observed. In 3 patients, analysis of the BAL fluid failed to yield a diagnosis. In the 11 patients with MH, 2 cases of CMV, 2 infections with Candida albicans and one with Aspergillus fumigatus were found. In 2 patients the pneumopathy was due to bacterial infection. Four BAL fluids failed to yield a diagnosis; however, in one of these transbronchial biopsy revealed interstitial pneumonia of unknown origin. On the basis of our material and comparison with clinica, radiological and serological data, it appears that BAL fluid analysis is a helpful and rapid diagnostic aid in infectious pneumopathies of immunocompromised patients. This is especially true of AIDS patients in whom the most common pulmonary complication is Pneumocystis carinii pneumonia. However, success of the analysis requires close cooperation between clinician, bacteriologist and pathologist.

Acquired Immunodeficiency Syndrome

Diffuse interstitial lung disease associated with hydrogen peroxide inhalation in a dairy worker.

A 41-yr-old dairy worker, smoker of 40 cigarettes daily, presented with severe gas exchange impairment caused by interstitial lung disease, as shown by transbronchial biopsy. He was exposed chronically to an aerosol of hydrogen peroxide (41 mg/mm3; upper legal limit: 1.5 mg/mm3) which must be incriminated as the etiologic agent, since withdrawal from exposure resulted in improvement, and no other etiology could be identified.

Adult

Interstitial pneumonitis and hepatitis after transfer of bone marrow cells bearing the lpr gene to irradiated recipients: a disease due to large granular leucocytes?

Mice bearing the 'auto-immune' lpr gene develop a lympho-proliferative disease associated with the production of various antibodies. Lethally irradiated recipients were grafted with bone marrow cells (BMC) from syngeneic mice with or without the lpr gene. After 6 months, the survivors were 0/24 and 16/20 for the recipients of lpr and normal BMC respectively. The mortality rate was independent of the presence of T lymphocytes among the BMC. Histological evaluation showed that hepatitis, interstitial pneumonitis, and sclerosis of lymphohaemopoietic organs were the major causes of death for the recipients of lpr BMC. Hepatitis was associated with an increase in the number of liver interstitial cells (LIC) from about 2 X 10(6) up to about 10(7) cells per liver. The LIC associated with the hepatitis were composed of polymorphonuclear leucocytes and large mononuclear leucocytes, showing phenotypic (i.e. Thy.1+, asialo GM1, presence of cytoplasmic granules) and functional (i.e. non-phagocytic and cytolytic) properties of NK cells. The disease can be distinguished both from the spontaneous disease of the lpr mice (by the absence of 'lpr cells' and of anti-DNA antibodies) and from graft versus host disease by the absence of cutaneous and intestinal lesions. It may represent a model of tissue injury mediated by large granular leucocytes.

Animals

Post-irradiation leiomyosarcoma. Case report with immunohistochemical studies.

We report here one case of post-irradiation leiomyosarcoma. The diagnosis of this was confirmed using anti-intermediate filament antibodies: tumor cells were positive for anti-vimentin and anti-desmin but negative for anti-prekeratin and anti-epithelial membrane antigen. The positive staining with anti-desmin clearly indicates a muscular origin although the tumor cells were not stained by two anti-actin antibodies, one directed against alpha-smooth muscle actin and the other against alpha-striated muscle actin. Irradiation was motivated by a wrong diagnosis of breast carcinoma when the patient was 13 year-old. The laps of time separating irradiation and the occurrence of the leiomyosarcoma was 13 years. The total dose was 6,000 rads. This is the ninth case of post-irradiation leiomyosarcomas reported in the literature.

Actin Cytoskeleton

Characterization of stromal cells with myoid features in lymph nodes and spleen in normal and pathologic conditions.

Stromal cells with myoid features were identified in rat or human lymph nodes and spleen in normal and pathologic conditions, using antibodies to desmin, alpha-smooth muscle actin, and smooth muscle myosin. In normal lymph nodes, myoid cells (MCs) were present in the superficial and deep paracortex as well as in the medulla, and absent in lymphoid follicles. In the spleen, they were numerous in the red pulp, less abundant in periarteriolar lymphocyte sheaths of the white pulp, and absent in lymphoid follicles. On double immunostaining, alpha-smooth muscle actin and smooth muscle myosin were coexpressed with desmin only in the deep paracortex and parafollicular areas of the lymph nodes, as well as in the MCs of the periarteriolar lymphocyte sheaths and marginal zone of the spleen; the remaining MCs expressed only desmin. When examined by means of electron microscopy, MCs showed a dendritic shape and cytoplasmic bundles of microfilaments with dense bodies scattered between them. When compared with normal conditions, MCs showed changes of distribution and number in several pathologic situations. Additional findings were 1) staining of pericytes surrounding high endothelium venules of lymph nodes with alpha-smooth muscle actin antibodies in man and rat and with desmin antibodies in rats; 2) staining of endothelial cells in these venules with desmin antibodies in rats. It is concluded that a subset of reticular cells in lymph nodes and spleen, as well as pericytes and endothelial cells in high endothelium venules display cytoskeletal features suggesting a myoid differentiation and function.

Actins

[Malignant paraganglioma of the duodenum. Immunohistochemical and ultrastructural study of a case].

Paragangliomas of the duodenum are rare. Only 40 cases, most of them corresponding to benign tumours, have been published. In this study, we report a malignant paraganglioma of the duodenum with lymph node metastasis occurring in a 73 year old woman. The essential clinical manifestations which brought the patient to surgery were abdominal pain, melaena and anemia. The surgical specimen was investigated histologically, immunohistochemically and ultrastructurally. The tumour was composed of three types of cells: epithelial, gangliocytic and spindle shaped mesenchymal cells. The first contained ultrastructurally intracytoplasmic granules bound with double membranes; they stained with monoclonal antibodies against chromogranin. Gangliocytic cells stained with monoclonal N.S.E. antibodies and the spindle cells stained with S 100 protein. The spindle cells displayed ultrastructurally glial cell characteristics, containing micro-filaments of glial type. These immunological and ultrastructural features argued in favor of the neuroendocrine cell origin of this paraganglioma.

Aged