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Biomedical subjects

C C Marboe

Publications and source records attributed to C C Marboe.

At least 55 records · Page 3Linked to original sources

Acute reoxygenation injury in the isolated rat heart: role of resident cardiac mast cells.

Leukocyte-mediated myocardial reperfusion injury is characterized by the progressive migration and accumulation of polymorphonuclear leukocytes within the myocardium. In this study, we hypothesized that leukocytes normally resident to the myocardium also contribute to myocardial injury in the absence of migration and accumulation of peripheral polymorphonuclear leukocytes. In isolated crystalloid-perfused rat hearts, we found numerous resident cardiac leukocytes that were identified primarily as macrophages and mast cells, the latter staining avidly for peroxidase. When hypoxic perfused hearts (60 minutes, n = 16) were reoxygenated there was a prompt release of this peroxidase activity, the extent of which correlated closely with the degree of myocardial injury (total creatine kinase release, r = 0.96). When reoxygenation associated mast cell degranulation was prevented in six additional hypoxic hearts using 10 microM Lodoxamide Tromethamine, peroxidase release was reduced 7.8-fold (p less than 0.001) and creatine kinase release (injury) was reduced 5.9-fold (p less than 0.001). These results demonstrate that the isolated crystalloid-perfused rat heart is not a leukocyte-free preparation and suggest that mast cells resident to the heart play an important role in acute reoxygenation injury.

Acute Disease↗

Biopsy diagnosis of myocarditis.

In closing, we can only note that none of the classification schemes for myocarditis has been perfect for clinicians, pathologists, and researchers alike. The definition and classification protocol offered by the "Dallas" group is based solely on histology, but we urge its use by physicians and other researchers as a means of imposing some standardization on the study of myocarditis. The question of optimum treatment, particularly immunosuppressive therapy, has never been definitively answered, but it is now clear that a large, multicenter randomized trial is the only proper method to search for such an answer. Standard nomenclature is a prerequisite for this study. In the meantime, the clinical correlates and prognostic utility of these histologic categories may be defined; these morphologic groupings will probably be shown to be clinically heterogeneous. In the end, we hope a hybrid clinical-pathologic scheme for the diagnosis and classification of myocarditis will be forged. Such a protocol, ideally, will allow the correlation of structure with function and also reliably predict clinical behavior and response to treatment so that someday we may be able to both counsel and cure persons with myocarditis.

Biopsy↗

Prolongation of primate cardiac xenograft survival with cyclosporine.

Cardiac xenotransplantation in nonprimates using traditional immunosuppression (azathioprine and prednisone) or cyclosporine has been unsuccessful or has required doses of immunosuppressants not tolerated by man. This study sought to determine if primate hearts could be transplanted successfully across genus boundaries using a dose of cyclosporine applicable to human transplantation. The hearts of outbred cynomolgus monkeys (Macaca fascicularis) were heterotopically transplanted into the necks of outbred baboons (Papio anubis). Hyperacute rejection did not occur and there were no cyclosporine-induced malignancies or nephrotoxicity. A 12-fold prolongation of mean cardiac xenograft survival to 77 days was accomplished using parenteral cyclosporine and steroids. The histology of rejection was notable for the appearance of reversible rejection on the 30-day biopsies. The histopathologic and immunologic data support the role of both cell-mediated and humoral mechanisms in primate cardiac xenograft rejection. Neither mixed lymphocyte cultures or cytotoxic antibody assays were predictive of graft loss, but there was a significant increase in their respective levels at the time of cessation of graft function. Thus, significant prolongation of primate cardiac graft survival across a genus boundary was accomplished using a dose of cyclosporine similar to that used in human transplantation.

Animals↗

Monoclonal antibody identification of mononuclear cells in endomyocardial biopsy specimens from a patient with rheumatic carditis.

A 17-year-old woman with rheumatic carditis underwent endomyocardial biopsy both prior to and following treatment with prednisone and aspirin. Frozen sections from the endomyocardial biopsy specimens were studied with monoclonal antibodies by an indirect immunofluorescence technique to define the composition of the inflammatory infiltrate in the myocardium and to determine whether the composition of the infiltrate is distinctive and diagnostically useful. The specimen from the initial biopsy contained a heterogeneous infiltrate composed of T lymphocytes, macrophages, B lymphocytes, and mast cells. T lymphocytes predominated, and the ratio of T-helper to T-cytotoxic/suppressor cells was 2.0. Following treatment the overall cellularity of the infiltrate was diminished, but the infiltrate remained heterogeneous; T cells predominated, and the T-helper to T-cytotoxic/suppressor ratio was reversed, to 0.59. The composition of the inflammatory infiltrate in this case of rheumatic carditis distinguishes it immunologically from other "idiopathic," presumably virus-associated, forms of myocarditis.

Adolescent↗

Chemotherapy and its effect on testicular morphology in children.

Bilateral testicular biopsies were performed on 25 boys between 4 and 16 years old with the diagnosis of acute lymphocytic leukemia after the induction of regression with vincristine and prednisone, followed by cyclic maintenance therapy with a combination of 6-mercaptopurine, methotrexate, L-asparaginase, cyclophosphamide and doxorubicin for 2 years. These drugs were given in accordance with children's cancer study group protocols. Only 3 boys had positive biopsies (12 per cent), although post-treatment testicular morphology was abnormal in the overwhelming majority. Interstitial fibrosis was present in 16 children (70 per cent), basement membrane thickening in 12 (50 per cent) and, most importantly, a reduction in the tubular fertility index of greater than 50 per cent in 20 (80 per cent). There was no relationship between the abnormal morphology encountered and the age of the patient when treated. Most of these changes may be reversible with time but only a biopsy at a later date can establish the long-term effects of treatment on testicular morphology and, perhaps, help to predict future fertility potential.

Adolescent↗

Distribution of antigens defined by OKB monoclonal antibodies on benign and malignant lymphoid cells and on nonlymphoid tissues.

Monoclonal antibodies OKB1, OKB2, OKB4 and OKB7 have been previously shown to detect distinctive antigens displayed on B, but not on T, lymphocytes. Benign and malignant lymphoid cells were investigated for their reactivity with these antibodies in cell suspension by indirect immunofluorescence and in cryostat tissue sections by the avidin-biotin complex immunoperoxidase technique. Fetal liver pre-B cells and pre-B and common type acute lymphoblastic leukemia cells isolated from 15 patients were OKB1-OKB2+OKB4-OKB7-. All mature lymphoid tissue B cells and the neoplastic cell surface immunoglobulin-positive (SIg+) B cells isolated from each of 47 B cell neoplasms were OKB2+. OKB1 and OKB7 were expressed by interfollicular, follicular center, and many, but not all, mantle zone B cells. OKB4 was expressed by follicular center cells, but not by mantle zone or interfollicular B cells. The neoplastic SIg+ B cells isolated from 45 of 47 B cell malignancies were OKB1+OKB4+, and those isolated from 45 of 46 B cell malignancies were OKB7+. The neoplastic B cells of one mantle zone lymphoma were OKB1-, of one small lymphocytic cell lymphoma were OKB7-, of one large cell lymphoma were OKB4-, and of one small lymphocytic cell lymphoma with a monoclonal gammopathy were OKB1-OKB4-. Normal and myeloma plasma cells were OKB-. The malignant T cells isolated from 12 T cell neoplasms were OKB2-OKB4-, but were OKB1+ and/or OKB7+ in 3 cases. Thus, the OKB antibodies appear to detect distinctive antigens that may be expressed at different stages of B cell differentiation. In addition, OKB4 reacted with selected renal and respiratory epithelium, and OKB2 reacted with a wide range of epithelial tissues. The OKB antibodies should prove useful in the investigation of B cell differentiation and may aid in the identification and characterization of lymphoproliferative malignancies with significant therapeutic and prognostic differences not identifiable by conventional histopathologic and immunologic methods.

Animals↗

A membrane antigen (HC1) selectively present on hairy cell leukemia cells, endothelial cells, and epidermal basal cells.

A monoclonal antibody (alpha HC1) raised against HCL cells reacted specifically with HCL cells and not with other normal or leukemic B cell types. It also reacted with BC and with vascular EC. One case of Kaposi's sarcoma, a tumor thought to derive from EC, was also stained by this antibody. Sinusoidal cells of liver and spleen and EC in the brain did not stain with alpha HC1, but EC from all other tissues and EC in culture were positive. Because the exact normal cell equivalent of the leukemic hairy cell is unknown, similarities in phenotype and function between EC and hairy cells are of particular interest.

Antibodies, Monoclonal↗

The immunologic and ultrastructural characterization of the cellular infiltrate in acute cardiac allograft rejection: prevalence of cells with the natural killer (NK) phenotype.

The inflammatory cell infiltrates in 15 endomyocardial biopsies serially obtained from a human cardiac allograft during a 1 1/2-year period were characterized. An indirect immunofluorescent technique with hybridoma-derived monoclonal antibodies which preferentially react with B lymphocytes (anti-Ia), mature T cells (OKT3, Leu 1), and helper (OKT4b,d) and supressor/cytotoxic (OKT8) T-cell subsets and with natural killer cells, macrophages, and granulocytes (OKM1) was used. During each of seven rejection episodes the overwhelming majority of infiltrating cells in the endomyocardial biopsy were OKM1+Ia. These cells displayed short microvilli, a moderate amount of cytoplasm, numerous mitochondria, a large amount of rough endoplasmic reticulum, Golgi, and an indented nucleus, that is, the ultrastructural features of large, granular lymphocytes. Thus, they morphologically and phenotypically resemble those lymphoid cells which have been shown to possess natural killer (NK) functions in man. Occasional Leu 1+OKT3+ cells, some of which were OKT8+, were also seen during acute rejection. In each instance following therapy and resolution of the rejection episode only rare OKM1+Ia- cells were present. At this time the majority of the cells were Leu 1+OKT3+OKT8+. Routine biopsies, performed at times without evidence of rejection, showed only reactivity for Ia antigens by the capillary endothelium. These studies demonstrate the prevalence of cells with the natural killer phenotype in this human cardiac allograft during episodes of acute graft rejection.

Acute Disease↗

Testicular biopsy and occult tumor in acute lymphocytic leukemia.

Testicular biopsy has become a routine procedure before discontinuing chemotherapy in male children being treated for acute lymphocytic leukemia (ALL). Before a decision can be made to discontinue multiple drug therapy, all possible sites of occult tumor such as the testis, cerebrospinal fluid, and bone marrow must be sampled. Between December, 1978, and November, 1981, 25 male children underwent testicular biopsies after two or more years of combination chemotherapy at the Babies Hospital, Columbia-Presbyterian Medical Center. Only 3 of the 25 patients (12%) were found to have leukemic infiltrates on histologic sections. Two of 3 patients, however, were noted preoperatively to have either irregular testicular contours or testicular enlargement and induration. Occult testicular infiltration discovered after two or more years of chemotherapy is rare. Most children with a histologically positive biopsy result were at least suspected preoperatively to have testicular involvement.

Adolescent↗