Biomedical subjects
Publications and source records attributed to M Schlesinger.
The peripheral blood lymphocyte subsets of 10 patients with rapidly progressive periodontitis were investigated with monoclonal antibody. In 4 patients, the T helper/T suppressor ratio was increased. 5 others had a slightly reduced T helper/T suppressor ratio as compared to control group. These findings may indicate a possible cellular immune response in the pathogenesis of rapidly progressive periodontitis.
The immunological and clinical effects of levamisole were studied in 10 children with frequently relapsing steroid responsive nephrotic syndrome (SRNS). The efficacy of the drug was tested during remission of the disease with all patients on alternate day steroid therapy. The lymphocyte proliferative response to phytohemagglutinin (PHA), concanavalin-A (Con-A) and pokeweed mitogen (PWM) were normal. The Con-A induced suppressor T-lymphocyte activity of 7 patients was low before treatment with levamisole 8 +/- 3.7% and increased to normal values during therapy 34 +/- 6%; p less than 0.001 (control 32 +/- 5%). In these 7 children prednisolone dosage could be decreased significantly or discontinued altogether (44.1 +/- 5.3%). Patients without immunoregulatory abnormalities did not respond to levamisole. In 3 out of 4 children tested the percentage of OKT8+ cells rose during levamisole therapy from 19.7 +/- 2.1 to 37 +/- 2.3 (p less than 0.001), thus correcting the elevated pre-treatment OKT4+/OKT8+ ratio from 3.1 +/- 0.2 to 1.5 +/- 0.2; p less than 0.001 (control 1.47 +/- 0.2). These data support the hypothesis that abnormal immunoregulation may play a role in the pathogenesis of SRNS. Treatment with levamisole can be useful in some patients with the frequently relapsing form of the disease.
The authors provide an overview of privatization, a major trend in mental health policy, focusing in particular on the reasons for and consequences of substantial growth and change in ownership of private psychiatric hospitals; the proportion of all nonfederal psychiatric inpatient beds in private facilities has increased from less than 10% in 1970 to 35% today. It is estimated that between 1970 and 1986, the proportion of total nonfederal psychiatric inpatient beds in the United States that were under corporate for-profit auspices increased from about 1% to 15%. The authors distinguish and examine several aspects of privatization and assess the implications of these changes for psychiatry and for public policy and research.
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Distinct monoclonal autoantibodies directed against the Thy-1 antigen differ in their reactivity with various target cells. The aim of the present study was to analyse the idiotypic specificities present on various monoclonal autoreactive Thy-1 antibodies. Xenogeneic anti-idiotypic (anti-Id) reagents were prepared by immunizing rabbits either with the 20-10-5 or with the C16-31 monoclonal Thy-1 autoantibodies. Both of the anti-Id reagents reacted with the immunizing MoAb in ELISA and inhibited the interaction of the immunizing MoAb with Thy-1-positive target cells. The anti-20-10-5 reagent reacted in ELISA inhibition tests with the C16-31 MoAb, yet failed to inhibit the binding of C16-31 MoAb to thymocytes. Anti-C16-31 Id reacted with the 20-10-5 MoAb both in ELISA assays and in cell-bound fluorescence inhibition tests. These results indicate that anti-C16-31 Id detects an Id determinant shared by C16-31 and 20-10-5 MoAb, which is a binding site-related idiotype, while anti-20-10-5 Id detects an idiotypic determinant shared by these two MoAb that is not located at the combining site of C16-31 MoAb. In contrast to the marked cross-reactivity found between C16-31 and 20-10-5 MoAb, the two anti-Id reagents showed only a weak cross-reactivity with five other Thy-1 autoantibodies tested, including those autoantibodies that showed patterns of reactivity similar to those of C16-31 and 20-10-5, with various target cells. It is concluded, therefore, that individual autoreactive Thy-1 MoAb possess distinctive idiotypic determinants, although some cross-reactivity can be detected between certain MoAbs.
The formation of rosettes with MRBC is not an exclusive property of chronic lymphocytic leukemia cells and of human B-lymphocytes. Human thymus cells and the HD-MAR T-cell line were also found to be capable of forming rosettes with MRBC. The binding of MRBC by thymocytes differed from that of sheep (SRBC), rabbit (RRBC) and human (HRBC) erythrocytes by a number of parameters: monoclonal antibodies against the E-receptor inhibited the attachment of SRBC, RRBC, and HRBC, but not of MRBC to thymus cells. The presence of EDTA had the opposite effect, abrogating only the attachment of MRBC to thymus cells but not of RBC from the other sources. Exposure of thymus cells to pronase eliminated their capacity to bind SRBC, RRBC, and HRBC, but only slightly inhibited the attachment of MRBC. Treatment with Vibrio cholerae neuraminidase enhanced the formation of rosettes with SRBC, RRBC, and HRBC, but had no effect on the formation of rosettes with MRBC. Exposure of thymus cells and of the HD-MAR cells to phospholipase C enhanced the proportion of rosettes formed with MRBC, but had no effect on the binding of other RBC. Treatment with either phospholipase A2 or phospholipase D had no such effect. The binding of MRBC by Raji cells was not increased by phospholipase C treatment. The present study indicates that the binding of MRBC by human thymus cells is mediated by receptors distinct from those involved in the binding of SRBC, RRBC, and HRBC and also from those mediating the binding of MRBC to human B-cells.
Rabbit antisera specific for idiotypic determinants (Id) of monoclonal Thy-1 autoantibodies were tested for their capacity to elicit Id-bearing thymus autoantibodies in mice. Rabbits were immunized with the 20-10-5 monoclonal IgM Thy-1 autoantibody, and idiotype-specific antibodies (anti-Id) were obtained by affinity chromatography. BALB/c and C3H mice were immunized by repeated i.p. injections of the anti-Id reagent. Control mice received repeated injections of purified normal rabbit immunoglobulin (NRIg) sheep red blood cells (SRBC) or human serum albumin (HSA). The sera of the treated mice were examined for their reactivity with anti-Id xenoantisera and for their capacity to react with thymus cells. The injection of anti-Id sera into either BALB/c or C3H mice resulted in a significant increase in the serum concentration of Id-bearing immunoglobulins, while no such change was observed in the sera of mice injected with NRIg. The administration of anti-Id, NRIg, SRBC or HSA resulted in a gradual increase in the concentration of autoantibodies reactive with thymus cells. Incubation with anti-Id sera prevented the binding to thymus cells of autoantibodies induced by anti-Id treatment. In contrast, the binding capacity of autoantibodies induced by NRIg, SRBC or HSA was unaffected by anti-Id sera. Thus, only the thymus autoantibodies induced by anti-Id treatment expressed Id-determinants. These results demonstrate the existence of a regulatory network in the formation of thymus autoantibodies.
This study was undertaken to investigate the effect of ketotifen on the immune system of asthmatic children receiving prophylactic treatment with ketotifen. E. rosettes, mitogenic response to phytohemagglutinin (PHA) and concanavalin A (Con A) as well as Con A induced suppression were measured in 15 asthmatic patients before and 1-3 months after treatment with ketotifen (1 mg x 2/day), and in 20 normal healthy controls. No significant difference in immunological parameters studied were found between the pre and post treatment periods in the asthmatic patients, neither was any difference demonstrated between the asthmatic and control group studied.
Measurements of cellular immunity including the percentage of T-cell mitogenic response of lymphocytes to phytohemagglutinin (PHA) and concanavalin A (Con A), as well as Con A-induced suppressor function, were determined in 20 asthmatic children (mean age 12.4 +/- 0.6 years) before and after 6 months of theophylline therapy. Only 9 of the 20 children patients that commenced the study completed the entire 6 months of therapy. A group of 37 healthy children (mean age 12.6 +/- 0.3 years) served as control. During the 6-month period of therapy, theophylline levels were maintained between 10 and 20 micrograms%. No significant difference in any of the parameters examined were found between the initial 20 asthmatic patients and the control group. Furthermore, in the 9 patients that were evaluated before and after 6 months of theophylline therapy no significant change in lymphocyte function including suppressor function was detected. We conclude that the beneficial effect of long-term theophylline therapy in asthmatic children is probably not related to an immuno-modulatory effect.
Erythrocyte glutathione peroxidase (GPX) levels were determined in 56 asthmatic children. Lowest levels were found during acute asthmatic attack (13.53 +/- 2.94 IU) which were significantly less than controls (20.4 +/- 5.44 IU) (P less than .001). Post-attack levels 1 week later rose significantly (16.77 +/- 2.63 IU), but were still less than normal values (P = .001). GPX levels (16.96 +/- 3.28 IU) were less than controls (P less than .03) even in patients with mild symptomatology. Asymptomatic patients receiving theophylline had normal levels. Low GPX activity in asthmatic patients may play a role in the pathogenesis of the disease.
Previous studies have indicated that the degree of stress controllability, rather than stress itself, may be a factor in immunosuppression. In the present study lymphocytes were obtained from individuals living in agricultural settlements in the Jerusalem area who are under the medical supervision of family-oriented primary health care clinics. Peripheral blood lymphocytes (PBL) obtained from married, adult males classified either as "copers" or as "non-copers" were tested for their natural killer (NK) activity and for the expression of the Leu 7 and Leu 11 NK-associated antigens. Differences were noted in the NK activity of PBL obtained from individuals belonging to various ethnic origins. Among Moroccan Jews the NK activity of non-copers was significantly lower than that of copers. In contrast, the proportion of PBL carrying antigenic markers of NK cells (Leu 7 and Leu 11) was higher among copers than among non-copers. Thus, psychosocial stress may lead in non-copers to decreased NK activity paralleled by an increase in the proportion of either immature pre-NK cells or possibly other immunoregulatory cells.
A 6-year-old Jewish Iranian girl with familial hemophagocytic lymphohistiocytosis (FHLH) is described. The course of the disease fluctuated with partial initial response to antibiotics, steroids, and supportive treatment. Subsequent cytotoxic treatment, including VP-16, Velban (vinblastine sulfate), and methotrexate (MTX) controlled the disease for a few months but the child died with a clinical picture of meningocephalitis 1.5 years later. Benign-looking lymphohistiocytic infiltrates with varying degrees of hemophagocytosis were present in the bone marrow, pleural effusion, cerebrospinal fluid (CSF), liver, and brain. Clinical and laboratory evidence of immunologic dysregulation during the disease could be demonstrated. Frequent and intense viral and bacterial infectious diseases were encountered. The laboratory examination most consistently found was the absence of natural killer (NK) cell activity against K562 target cells. The impaired activity of NK cells persisted during all stages of the disease including remission, although NK cell numbers, determined morphologically and immunophenotypically (by Leu-11, Leu-7), were normal. Natural killer activity could not be restored by interferon. Moreover, the interferon system appeared to be intact. Impaired monokin interleukin 1 (IL-I) production by peripheral blood monocytes was found and could not be restored by indomethacin. Lymphopenia, a mild decrease in T4 numbers, and subsequently, decreased proliferative response to mitogens was noted. Elevated immunoglobulin levels were found during exacerbations and viral episodes, at times accompanied by the presence of auto-antibodies. The exaggerated fatal lymphohistiocytic response typical for FHLH could be attributed to a underlying genetic pathologic dysregulation of the various immunological response pathways.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
The contemporary expansion of investor-owned health care facilities has stimulated much controversy but little response from policymakers. We believe this results from the apparently ambiguous relationship between ownership and socially valued outcomes. In our assessment, this ambiguity occurs largely because the effects of ownership are mediated in complex ways by characteristics of the services being delivered and the training of health care providers. Reviewing both the history and current performance of nonprofit and for-profit health care facilities, we identify some of the more important of these mediating factors. Taking these into account, there is a consistent influence of ownership on the delivery of health services. On the basis of this analysis, we discuss appropriate policy responses to the future growth of investor-owned health care organizations.