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Biomedical subjects

C C Marboe

Publications and source records attributed to C C Marboe.

69 records · Page 4Linked to original sources

Human sympathetic ophthalmia. An analysis of the inflammatory infiltrate by hybridoma-monoclonal antibodies, immunochemistry, and correlative electron microscopy.

A case of human sympathetic ophthalmia, enucleated after surgical trauma, was studied by means of hybridoma-derived monoclonal antibodies, histochemistry, and transmission electron microscopy. The choroidal infiltrate was composed predominantly of T-lymphocytes of the suppressor/cytotoxic subset (OKT8+); only 5% of the cells were immunoglobulin-producing B-lymphocytes (kappa or lambda light chain positive), thereby explaining the well-known paucity of plasma cells in the infiltrate. The epithelioid cells and phagocytic histiocytes in the choroid were la+ and OKM1+, antigenic determinants specific for bone marrow-derived monocytes, and their cytoplasms exhibited histochemical reactivity for alpha-1-antichymotrypsin and lysozyme. Ultrastructurally, the choroidal epithelioid cells contained single melanin granules in the cytoplasm, but these were membrane-bound and frequently associated with lysosomal material, features militating against these cells being transformed choroidal melanocytes. By means of immunologic and ultrastructural analysis, the Dalen-Fuchs nodules were found to be composed of a mixture of histiocytes (la+ and OKM1+) and depigmented retinal pigment epithelial cells (la- and OKM1-); the latter cells focally formed desmosomes and displayed inclusions of lipofuscin. Scattered within the Dalen-Fuchs nodules were small numbers of T-lymphocytes of the suppressor/cytotoxic subset. We have concluded that the uveitis and retinal pigment epithelial changes are mediated by a T-cell, delayed hypersensitivity pathogenetic mechanism (cell-mediated immunity), possibly directed at surface membrane antigens that may be shared by photoreceptors, retinal pigment epithelial cells, and choroidal melanocytes.

Animals↗

A new human B-lymphocyte surface antigen (BL 2) detectable by a hybridoma monoclonal antibody: distribution on benign and malignant lymphoid cells.

A hybridoma-derived monoclonal antibody, produced by immunization with the Burkitt's tumor-derived B-lymphoblastoid cell line, B35M, was previously shown to detect a 68,000 dalton surface membrane protein, BL2, on the surface of peripheral blood B cells, which is absent from thymocytes, T cells, and granulocytes. In this study, we investigated the expression and distribution of BL2 on benign and malignant human lymphoid cells. Indirect immunofluorescent assay with this monoclonal antibody demonstrated that BL2 is expressed by cells within the fetal liver and by a variable proportion of lymph node, tonsil, and spleen B cells, but not by T cells. The neoplastic cells isolated from 18 T-cell malignancies were BL2- . BL2 was was heterogeneously expressed by a variable proportion of the malignant cells in 29/32 cases of B-chronic lymphocytic leukemia and 33/38 cases of B-cell lymphomas, but appeared to be lost in the terminal stages of B-cell differentiation, as myeloma plasma cells were BL2- . BL2 expression was not limited to B cells of a particular surface immunoglobulin isotype. Immunofluorescent staining for BL2 in cryostat tissue sections demonstrated that the majority, but not all, germinal center and interfollicular Ia+ (non-T) cells are BL2+. These findings suggest that BL2 is a B-cell lineage-specific differentiation marker that may be useful in the study of B-cell ontogeny and in defining subgroups of the B-cell malignancies.

Antibodies, Monoclonal↗

Chronic erosive gastritis: clinical, diagnostic, and pathological features in nine patients.

We have recognized nine patients with gastric mucosal lesions which were characterized by an erosion with surrounding mucosal elevation. This lesions has previously been called chronic erosive or varioliform gastritis. Patients were investigated because of upper gastrointestinal symptoms (n = 7), weight loss (n = 2), and/or bleeding (n = 3). Radiologically the appearance was of typical target lesions. Pathological features included pseudopyloric metaplasia, pyloric gland hyperplasia, acute and chronic inflammation, edema, and fibrosis. Atypia was present in biopsies from four patients and in one was incorrectly interpreted as representing intramucosal carcinoma. The remaining patients were treated with antacids and/or cimetidine with resolution of symptoms and in five patients repeat endoscopy demonstrated resolution of the lesions. Chronic erosive gastritis may cause upper gastrointestinal symptoms indistinguishable from peptic ulceration. Greater numbers of patients will have to be treated in a controlled fashion to determine the natural history of the disease and the most efficacious treatment.

Chronic Disease↗

Perinatal death due to abruptio placentae in an African city.

Abruptio placentae was a common cause of perinatal death in Addis Ababa, Ethiopia in 1974-1975 with a frequency of 5.5/1000 births. This disorder had its peak frequency at term. No abnormalities were found in the placentas to explain the placental abruptions but there were other clues to their genesis. There was a strong association of the fatal abruptions with severe poverty in the mothers. These poor mothers were both undernourished and malnourished during pregnancy. Their fetuses and neonates who died had multiple evidences of undernutrition including a relative undergrowth of adrenals, spleens and livers and a relative acceleration of lung maturation. These findings support observations in more prosperous nations that poor nutrition of the gravida may have an important role in the genesis of abruptio placentae.

Abruptio Placentae↗

Twins: causes of perinatal death in 12 United States cities and one African city.

The perinatal mortality rate in a large U. S. study was 139 per 1,000 births for twins and 33 per 1,000 for singletons. Sixteen per cent of the twin deaths were due to amniotic fluid infections, 11 per cent to premature rupture of the membranes, 8 per cent to the monovular twin transfusion syndrome, 8 per cent to large placental infarcts, 7 per cent to congenital anomalies, and the rest to over 20 other disorders. The perinatal mortality rate for monozygotic twins was 2.7 times that for dizygotic twins, mainly due to more amniotic fluid infections, congenital anomalies, and the twin transfusion syndrome in the monozygotic pairs. To study the role of poor maternal nutrition on twins, a similar study of perinatal mortality rates was undertaken in Addis Ababa, Ethiopia. Addis Ababa twins had 2.5 times the mortality rate of U. S. twins, mainly due to a higher frequency of amniotic fluid infections, abruptio placentae, cord accidents, obstructed labors, congenital syphillis, and the twin transfusion syndrome in the Ethiopians.

Abruptio Placentae↗

Causes of perinatal mortality in an African city.

Little has been published about the causes of most of the deaths responsible for the high perinatal mortality rates characteristic of preindustrial, urban societies. The present study searched for answers in one such society by identifying the causes of death in a large-scale analysis of perinatal mortality in Addis Ababa, Ethiopia. A 72% autopsy rate was achieved when 1019 postmortem examinations were performed for 1424 consecutive perinatal deaths. The overall perinatal mortality rate was 65.3 per thousand live births. The ratio of stillbirths to neonatal deaths was 2.7:1, indicating that maternal factors were dominant in causing the deaths. One-third of the deaths were due to amniotic fluid infections, 15% to obstructed labour, 8% to abruptio placentae, and the rest to more than 20 other specific disorders.

Ethiopia↗

Photochemotherapy in human heart transplant recipients at high risk for fatal rejection.

Heart transplant recipients in whom high levels of lymphocytotoxic antibodies directed towards a spectrum of histocompatibility antigens develop frequently represent difficult management problems. Recipients of multiple transplants and multiparous females generally form higher levels of panel reactive antibodies, which have been associated with fatal rejection episodes and accelerated graft atherosclerosis. In this study, two multiple transplant patients with preexistent high levels of panel reactive antibodies and two multiparous women who were considered at risk of sensitization were treated with a new form of immunotherapy termed photochemotherapy in addition to conventional immunosuppression. High levels of panel reactive antibodies have been reduced, and patients have suffered few rejection episodes and no infectious complications. This preliminary experience shows that the addition of photochemotherapy to conventional regimens may improve the clinical course of hypersensitized transplant patients without additional immunosuppressive risk.

Adult↗

Vascular (humoral) rejection in human cardiac allograft biopsies: relation to circulating anti-HLA antibodies.

Vascular or humoral rejection (as defined by linear deposits of immunoglobulin and complement in myocardial capillaries) and the presence of circulating lymphocytotoxic anti-HLA antibodies are each associated with reduced long-term graft or patient survival. The relationship between these two factors has not been determined. We used immunofluorescent techniques to study 46 cardiac biopsy specimens in 16 patients from 15 to 412 days after transplantation. Biopsy specimens were selected from the first 2 months, and at approximately 6 and 12 months after transplantation and did not include episodes of acute cellular rejection. Each specimen studied was compared to a serum sample drawn an average of 1.8 days (range, 0 to 9 days) from the time of biopsy to assay for circulating anti-HLA antibodies. Of the specimens obtained at or near a positive anti-HLA antibody test, 90% (27 of 30) were found to have linear deposits of immunoglobulin (not necessarily with complement) versus 75% (12 of 16) of specimens obtained at the time of a negative test. Twenty-one cases of vascular rejection were documented. Both immunoglobulin M and immunoglobulin G were deposited along with complement in 13 instances; immunoglobulin M and complement were deposited in eight cases; no case had only immunoglobulin G and complement. The presence of circulating anti-HLA antibody in the serum was associated with 14 of the 21 cases of vascular rejection. Linear deposits of immunoglobulin in the capillaries of myocardium were frequently observed when anti-HLA antibodies were present in the serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of simultaneous lung transplantation on heart transplant survival in rats.

Clinical observations in humans reveal that heart-lung transplant recipients suffer significantly less cardiac rejection than those receiving only heart transplants. A heterotopic combined heart-lung model in rats was used to test the hypothesis that the presence of the lung in this combination increases survival of the heart transplant. Cardiac survival was compared between en bloc heart-lung transplants and heart transplants. Low dosages of cyclosporine were used to prolong but not prevent the rejection process. Heart graft survival in the cyclosporine, 1 mg/kg/day, groups was significantly prolonged in heart-lung allografts. Histologic studies also demonstrated more advanced rejection of the heart in the heart-only transplant groups as compared with the heart-lung transplant groups. This study shows that the presence of the lungs in heart-lung allografts provides for prolongation of cardiac survival.

Animals↗