Biomedical subjects
R Schroff
Publications and source records attributed to R Schroff.
Human melanoma-associated antigens: analysis of antigenic heterogeneity by molecular, serologic and flow-cytometric approaches.
The relationship of antigenic heterogeneity to the epitope recognized by an antibody was examined with monoclonal antibodies to human melanoma-associated antigens. Expression of the human melanoma-associated antigens, 250-Kd glycoprotein/proteoglycan and p97, was examined quantitatively by flow cytometry on fresh cell suspensions of human melanoma. Percent positive cells and mean fluorescence intensity were consistently higher with antibody 9.2.27 to the 250-Kd glycoprotein/proteoglycan than with antibody to p97. In addition, assessment of percent positive cells in multiple skin lesions biopsied from individual patients indicated that in 26 of 30 lesions, greater than 90% of the cells stained positively with 9.2.27. This relative lack of antigenic heterogeneity with antibody 9.2.27 contrasted with previous reports which showed considerable antigenic heterogeneity with other antibodies to the 250-Kd glycoprotein/proteoglycan. The explanation for this distinction was sought by quantitative flow cytometric and sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) techniques. Comparison by flow cytometry and immunoperoxidase of three antibodies, which recognized distinct epitopes of the 250-Kd glycoprotein/proteoglycan, indicated that 9.2.27 reacted more intensely with cultured cells and tissue sections than other antibodies to the same antigen. Examination by SDS-PAGE indicated that 9.2.27 could immunoprecipitate a larger proportion of 250-Kd glycoprotein molecules than other antibodies. In addition, immunodepletion experiments in gels indicated that the 9.2.27 determinant was present on a higher proportion of 250-Kd glycoprotein molecules than PG-2 antibody to a separate determinant. It is likely that 9.2.27 antibody displays less antigenic heterogeneity because its epitope is represented on a higher proportion of the antigen molecules. Thus, not only the nature of the antigen but also the epitope recognized by an antibody influences the degree of antigenic heterogeneity.
Aortico-left ventricular tunnel: late follow-up.
Since 1970, 6 patients have undergone repair of aortico-left ventricular tunnel. Four (67%) had repair in childhood. The technique of closure was by direct suture (5 patients) or patch closure (1 patient). Associated anomalies were seen in 5 patients (83%); absent right coronary ostium (1), commissural fusion (stenosis) (2), valvular regurgitation (3), leaflet defects (2), and healed endocarditis (1). All patients survived operation. At early postoperative review, 67% had mild aortic regurgitation regardless of the technique of surgical repair. Late follow-up revealed that 3 patients (50%) underwent aortic valve replacement (AVR) for progressive aortic regurgitation at a mean of 10 years following initial operation. A review of the literature and our results lead us to conclude that progressive aortic regurgitation is common; it is due to associated valve abnormalities and changes in the valve mechanism secondary to the aortico-left ventricular tunnel. Long-term clinical follow-up is necessary, since 50% of patients will require AVR eventually. Early operation is indicated not only to prevent heart failure but also to prevent progression of damage to the aortic valve.
Cell mediated inhibition of erythropoiesis and megaloblastic anemia in T-cell chronic lymphocytic leukemia.
A patient with T-cell chronic lymphocytic leukemia presented with severe megaloblastic anemia with normal serum folic acid and cobalamin concentrations. BFU-E could not be cultured from the patient's peripheral blood unless T-lymphocytes were removed by E-rosette formation. Inhibitory activity by the patient's T-cells was restricted to autologous BFU-E. After cyclic chemotherapy the anemia and megaloblastic changes resolved, peripheral blood BFU-E could be cultured from unfractionated peripheral blood and the T-cell inhibitory activity could no longer be demonstrated. The anemia in this patient is probably due to the neoplastic expansion of a suppressor T-lymphocyte population.
Immunoregulatory T cells in men with a new acquired immunodeficiency syndrome.
We have evaluated the functional properties of the OK-T8+/OKT4+ T-cell subpopulations in nine patients with a new syndrome of acquired immune deficiency (AIDS). Despite polyclonal hypergammaglobulinemia in the sera of these patients, their peripheral blood lymphocytes (PBL) produced negligible quantities of immunoglobulin (Ig) when cultured in vitro for 8 days in the presence of pokeweed mitogen (PWM). Patient B cells, however, synthesized normal quantities of immunoglobulin when cocultured with T cells from healthy donors, indicating preservation of B-cell function. Unfractionated PBL or T cells of patient origin mediated marked suppression of pokeweed mitogen-driven immunoglobulin production by T and B cells from healthy donors. The suppressive activity was contained within the population of T cells bearing the OKT8 antigen and was sensitive to in vitro irradiation. On a per-cell basis, patient OKT8+ cells appeared to have greater suppressive activity than normal control OKT8+ cells. In addition, OKT4+ cells from patients had less helper activity for induction of immunoglobulin synthesis than control OKT4+ cells. Increased T suppression and reduced T help are probably a consequence of one or more viral infections and may contribute to progressive immune deficiency and susceptibility to malignancy in patients with the acquired immuno deficiency syndrome.
Effect of midbrain stimulus-induced analgesia on immune function in humans.
Electrical stimulation of midbrain structures produces significant and clinically useful analgesia in humans. However, it has been suggested to have immunosuppressive effects in animals. We evaluated immune function in two women who were utilizing implanted midbrain electrodes for pain control. An elevated B cell percentage was observed in one patient after a 72-h control rest period and this was followed by a reproducible fall in B cells after acute stimulation. However, midbrain electrical stimulation did not appear to have any other acute or chronic effects on these persons' immune functions.
Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency.
Four previously healthy homosexual men contracted Pneumocystis carinii pneumonia, extensive mucosal candidiasis, and multiple viral infections. In three of the patients these infections followed prolonged fevers of unknown origin. In all four cytomegalovirus was recovered from secretions. Kaposi's sarcoma developed in one patient eight months after he presented with esophageal candidiasis. All patients were anergic and lymphopenic; they had no lymphocyte proliferative responses to soluble antigens, and their responses to phytohemagglutinin were markedly reduced. Monoclonal-antibody analysis of peripheral-blood T-cell subpopulations revealed virtual elimination of the Leu-3 / helper/inducer subset, an increased percentage of the Leu-2 + suppressor/cytoxic subset, and an increased percentage of cells bearing the thymocyte-associated antigen T10. The inversion of the T/ helper to suppressor/cytotoxic ratio suggested that cytomegalovirus infection was an important factor in the pathogenesis of the immunodeficient state. A high level of exposure of male homosexuals to cytomegalovirus-infected secretions may account for the occurrence of this immune deficiency.