Search PubMed⌕ Search

Biomedical subjects

M Schlesinger

Publications and source records attributed to M Schlesinger.

At least 199 records · Page 11Linked to original sources
PubMed1985

Implication of the Thy-1 antigen on mouse thymus cells in the recognition of 'self' structures.

Thymus cells of mice form rosettes with autologous and allogeneic erythrocytes. The nature of the thymus cell receptors which mediate the binding of erythrocytes is not known. The aim of the present study was to determine the effect of various antisera to T-cell specific antigens on the formation of rosettes by mouse thymus cells. In all strains of mice tested, the exposure of thymus cells to rabbit anti-mouse brain serum (RABR) was found to inhibit autorosette formation. Similarly, monoclonal Thy-1 antibodies inhibited the formation of autorosettes by thymus cells in all strains tested. Monoclonal antibodies against Lyt-1, Lyt-2, and TL determinants had no such effect. Monoclonal Thy-1 antibodies inhibited the formation of rosettes with allogeneic erythrocytes only when the thymus contained the Lyt-2.2 allele (BALB/c, C57BL), but not when it contained the Lyt-2.1 allele (AKR/J, C3H, DBA/2). These results indicate that Thy-1 determinants on thymus cells are involved in the recognition of 'self' structures, shared by erythrocytes of all strains of mice. Lyt-2 determinants may play a role in the recognition of 'non-self', allogeneic determinants, but the thymus cell surface structures encoded by the two Lyt-2 alleles may differ in their affinity to allogeneic erythrocytes.

Animals↗
PubMed1985

The expression of Leu M4 on human NK cells.

Previous studies have shown that the Leu M4 monoclonal antibody reacts strongly with human granulocytes in the peripheral blood, has a weak reactivity with monocytes but fails to react with platelets, eosinophils and K-562 cells. In the present study Leu M4 antibody was found to react with human NK cells. Immunofluorescent analysis indicated that about 12% of peripheral blood lymphocytes (PBL) are positive for this marker, and that the reactive cells are concentrated in the Percoll fraction known to display the strongest NK activity. Exposure of PBL to Leu M4 and complement resulted in a significant decrease of their NK activity. The relationship of Leu M4 to other monoclonal antibodies reactive with human neutrophils and NK cells remains to be elucidated.

Antibodies, Monoclonal↗
PubMed1985

Is common variable hypogammaglobulinemia linked to HLA? A family study.

Two patients with common variable hypogammaglobulinemia (CVH) and their families, who came from different ethnic backgrounds, were surveyed for the level of immunoglobulins (Ig) and HLA genotypes. Six of 10 siblings and the mother in one family had a decreased level of one of the major classes of Ig (IgA in 5, IgM in 1 and IgG in the mother). A similar decrease was found in three of six siblings in the other family (IgG in one, IgA in one and IgM in one). HLA genotyping disclosed that affected and nonaffected family members had identical genotypes, suggesting that hypogammaglobulinemia in CVH is not linked to a specific HLA genotype.

Adolescent↗
PubMed1984

Ownership and mental-health services. A reappraisal of the shift toward privately owned facilities.

The mental-health system in the United States is undergoing marked "privatization"--a growth in the importance of both private nonprofit and for-profit providers. Analyzing data collected in earlier surveys, we found that the type of ownership was linked to a number of important aspects of institutional performance: (1) private facilities, both for profit and not-for-profit, are more likely to screen out nonpaying patients than are government-owned providers; (2) services provided under public auspices are more expensive than those provided in private institutions; and (3) compared with private nonprofit facilities, for-profit providers devote fewer staff resources to patient care and offer fewer services with community-wide benefits. We conclude that ownership affects the organizational behavior of mental-health facilities. The contemporary shift from public to private provision of mental-health care raises important questions about ensuring adequate access to care, maintaining the supply of needed services, and adapting systems of reimbursement and regulation to the heterogeneous motivations of providers operating under different forms of ownership.

Community-Institutional Relations↗
PubMed1984

Surface antigen determinants in subpopulations of peripheral blood NK- and T-cells separated by Percoll density fractionation.

Subpopulations of NK-cells recovered in various Percoll fractions had similar Leu 7 (HNK-1) antigenicity. Leu 11 paralleled Leu 7 in its expression in the high density Percoll fractions, while cells in the lowest density showed a somewhat higher reactivity with Leu 11 than with Leu 7 antibody. A similar small proportion (20-30%) of NK-cells recovered in all Percoll fractions was susceptible to lysis by treatment with T8 and complement. Exposure to T11 and complement, which eliminate approximately 50% of the NK activity in unfractionated PBL, reduced the cytotoxicity of NK-cells recovered in the high density fraction to a significantly greater extent (60%) than that of those recovered in the low density (30%). Flow microfluorometry analysis using monoclonal anti-T reagents showed that while Leu 4 (pan T-marker) was expressed on all high density T-cells, a subpopulation of low density T-cells did not express this antigen. The proportion of Leu 3a positive (helper T) cells was found to be significantly higher among the high density T-cells than among the low density T-cells. There was a relative enrichment of Leu 2a positive (cytotoxic/suppressor T) cells recovered in the lower density Percoll fractions. Subsets of NK- and T-cells, differing in their density, were thus shown to also differ in their cell surface antigenic markers. Percoll density fractionation may prove to be a valuable tool for separation and analysis of NK- and T-cell subsets.

Antibodies, Monoclonal↗
PubMed1984

E-receptors mediate the attachment of activated T-lymphocytes to human red blood cells: evidence from studies with monoclonal antibodies and simple sugars.

Lectin-stimulated human T-lymphocytes display the capacity of forming stable E-rosettes with sheep red blood cells (SRBC) and of forming rosettes with allogeneic and autologous erythrocytes (RBC). Fractionation experiments indicated that the same subpopulation of lymphocytes displays both of these characteristics. Exposure of T-lymphocytes stimulated with concanavalin A (Con A) or phytohemagglutinin (PHA) to T11 monoclonal antibody (directed against the E-receptor) completely blocked the formation of rosettes with human RBC. Monoclonal antibodies to other T-cell surface markers (Leu 4, T4, T8 and OKT9) had no such effect. The formation of human RBC rosettes and stable E rosettes by PBL stimulated for 2 to 8 days by Con A was inhibited to a similar extent by dilutions of T11 monoclonal antibody. Lectin-stimulated PBL were exposed to various sugars to determine their effect on human RBC rosette formation. Rosette formation was inhibited over 80% with 2-deoxy-D-glucose and by 50-70% with D-mannose, while the other sugars tested had either less effect or none. The present findings support the concept that E-receptors on the surface of human T lymphocytes play a role in the recognition of carbohydrate containing "self" structures.

Adult↗
PubMed1984

Inhibition of human natural killer activity by 2-deoxy-D-glucose and other sugars.

The specificity of natural killer (NK) cells is still a matter of debate. In the present study a number of sugars were tested for their capacity to inhibit the NK activity of human peripheral blood lymphocytes (PBL) on K-562 target cells. The most pronounced inhibitory effect was exerted by 2-deoxy-D-glucose and 2-amino-D-glucose. Significant, though more variable inhibition was observed with D-fucose, D-ribose, L-rhamnose, and galactose. The inhibitory activity of the sugars was similar in NK assays carried out with target cells grown either in fetal calf serum or in normal human serum. 2-deoxy-D-glucose and 2-amino-D-glucose were shown to exert their inhibitory activity on effector rather than on target cells. They inhibited to a similar extent the NK activity of both unstimulated and interferon stimulated PBL. These 2 sugars also attenuated the antibody-dependent cell mediated cytotoxicity of PBL. The inhibitory effect of 2-deoxy-D-glucose and 2-amino-D-glucose on NK activity was not reversed by simultaneous exposure of NK cells to these inhibitors and glucose. The inhibitory effect of various sugars could result from the blocking of receptors on NK cells which recognize carbohydrate moieties on target cells. The activity of 2-deoxy-D-glucose and 2-amino-D-glucose could reflect impairment of the glycolytic pathway in the effector cells by the intracellular accumulation of phosphorylated derivatives of these inhibitors.

Adult↗
PubMed1983

The role of E receptors in the attachment of thymocytes and T lymphocytes to human target cells.

Human thymocytes, activated T lymphocytes, and neuraminidase-treated T cells possess the distinct capacity of forming conjugates with various human cell lines. The present study investigated whether E receptors, which endow human T cells with their capacity to bind sheep red blood cells (SRBC), are involved in this phenomenon. Monoclonal antibodies to human T cells and various simple sugars were studied for their effect on the attachment of human T cells to target cells. A-22, a monoclonal antibody to the E receptor, inhibited the formation of E rosettes by T cells and SRBC, and reacted in immunofluorescent-staining assays with the majority of human thymocytes and peripheral T cells, and with T-cell lines capable of forming E rosettes. When human thymus cells were treated with A-22 antibody they showed a reduction of up to 70% in their capacity to attach to the GM-4762 lymphoblast cell line and the K-562 myeloid line. Antibody treatment of the target cells, rather than of the thymus cells, had no effect on the formation of conjugates between thymus cells and target cells. Treatment of thymus cells with various monoclonal antibodies to T cells which do not react with the E receptor had no inhibitory effect. The exposure of human thymus cells to various simple sugars (D-mannose, D-fucose, galactose, and lactose) markedly reduced their capacity of forming conjugates with target cells. Exposure of neuraminidase-treated peripheral blood lymphocytes and of activated T cells to A-22 antibody inhibited their attachment to human target cells. The present study suggests that E receptors play a role in the attachment of human thymus cells and activated T cells to other human cells, and raises the possibility that these T-cell receptors may be involved in the process of recognition of "self" structures by human T lymphocytes.

Antibodies, Monoclonal↗
PubMed1983

Nailfold capillary abnormalities in childhood rheumatic diseases.

The nailfold capillary patterns of 84 patients with a variety of childhood rheumatic diseases and 34 normal control subjects were observed. Distinctive morphologic abnormalities with capillary dilation and dropout of surrounding structures were noted in two groups: patients with childhood dermatomyositis and with scleroderma (P less than 0.001). Among those with scleroderma, capillary abnormalities were found in all nine patients with systemic disease and in none of 10 patients with cutaneous disease only (Fisher's exact P less than 0.001). Of 25 patients with dermatomyositis for whom muscle biopsies were available for analysis, abnormal nailfold capillary pattern was found with highest prevalence in patients with two or more specific vascular lesions noted on biopsy (Fisher's exact P = 0.041). Nailfold capillary abnormalities are present in distinct populations of childhood rheumatic diseases, reflect the underlying vasculopathy of childhood dermatomyositis, and may be of diagnostic value in distinguishing localized from systemic scleroderma.

Adolescent↗
PubMed1983

Cell mediated immunity and effects of "thymic humoral factor" in 15 patients with SSPE.

Cell mediated immunity (CMI) in 15 patients with subacute sclerosing panencephalitis (SSPE) was assessed by E-rosette formation, leucocyte migration inhibition factor (LIF) production, and proliferative responses to mitogens. In eleven patients, one or more of these parameters were impaired. These defects varied among the different patients and no consistent or uniform pattern of immune deficiency could be demonstrated. Although no single patient had a generalized reduction of all the T-cell functions, a diminished percentage of E-rosetting cells was the most frequent abnormal parameter (7 out of 15 patients). There was no correlation between the clinical state of the patients and the immune defects. Thymic humoral factor (THF), a thymic hormone, reconstituted at least one CMI impaired function especially the reduced levels of E-rosette forming cells in 7 out of 9 patients. It seems unlikely that a generalized cell-mediated defect is the underlying cause of this disease, but immunomodulatory therapy should be considered in some selected cases.

Child↗
PubMed1983

A case of familial Mediterranean fever with cutaneous vasculitis and immune complex nephritis: light, electron, and immunofluorescent study of renal biopsy.

A 29-year-old patient suffering from familial Mediterranean fever developed severe myalgia and hematuria. Skin biopsy showed vasculitis. The kidney biopsy revealed diffuse proliferative and exudative glomerulonephritis. On immunofluorescent examination, IgM deposits accompanied by C3 were found in coarse granular peripheral distribution. Electron microscopy revealed glomerular subepithelial deposits. Familial Mediterranean fever with vasculitis and immune complex nephritis is discussed.

Adult↗
PubMed1983

Effect of colchicine on immunoregulatory abnormalities in familial Mediterranean fever.

The effect of colchicine on immunoregulatory T lymphocytes in children with familial Mediterranean fever (FMF) was studied. Concanavalin A (Con A)-induced suppressor cell function was significantly (P less than 0.0001) decreased in five untreated FMF patients (15 +/- 3%, mean +/- s.e.) as compared to six age matched paediatric controls (46 +/- 3%) and eight healthy adults (49 +/- 4%). When the five untreated FMF patients' mononuclear cells were pre-incubated in vitro with Con A plus 10(-5) M colchicine, their suppressor cell function was significantly increased (52 +/- 10%, P less than 0.01). Similarly, oral colchicine treatment (0.5 mg twice daily) significantly (P = 0.02) increased the five FMF patients' Con A-induced suppressor cell function to levels (34 +/- 6%) that were not significantly (P greater than 0.05) different than the paediatric controls or the healthy adults. The percentage of OKT8+ cells (but not OKT3+ or OKT4+ cells) was significantly (P less than 0.0001) decreased in 10 untreated FMF patients (16.0 +/- 0.9) as compared to 10 paediatric controls (27.6 +/- 2) or 10 healthy adults (25.7 +/- 0.6). The 10 untreated FMF patients had a significant (P less than 0.002) increase in the OKT4/OKT8 ratio (2.41 +/- 0.13) as compared to 10 FMF patients treated with 0.5 mg twice daily of colchicine (1.81 +/- 0.08), 10 pediatric controls (1.47 +/- 0.2), or 10 healthy adults (1.78 +/- 0.11). Colchicine appears to have corrected the FMF patients' elevated OKT4/OKT8 ratio by both decreasing the percentage of OKT4+ cells and increasing (but only partially correcting) the percentage of OKT8+ cells. Thus FMF patients have a suppressor cell deficiency in which colchicine treatment corrects their deficiency of Con A-induced suppressor cell function and their elevated OKT4/OKT8 ratio. This raises the possibility that colchicine might be potentially useful as an immunomodulating drug in treating patients with autoimmune or allergic diseases associated with a suppressor cell deficiency.

Adolescent↗
PubMed1983

Cell surface receptors involved in the attachment of murine cytotoxic T lymphocytes to target cells - a study with xenoantisera to T-cell antigens.

In previous studies it was demonstrated that rabbit anti-mouse thymus sera (RAT) but not rabbit anti-brain serum (RABR), block the activity of cytotoxic T lymphocytes (CTL). The aim of the present study was to determine to what extent inhibition of the lytic activity of CTL reflects inhibition of the attachment of CTL to target cells. Following heat inactivation RAT and RABR were absorbed with mouse liver and kidney and tested for their capacity to inhibit the attachment of sensitized peritoneal exudate T lymphocytes (PEL) to various target cells. The exposure of sensitized PEL to RABR markedly reduced their capacity to form conjugates with either allogeneic or syngeneic target cells. In contrast, RAT inhibited only the formation of conjugates of sensitized PEL with the respective target cells against which they were immunized. Treatment with RAT had no effect on the formation of conjugates with irrelevant target cells. Additive experiments in which PEL were exposed to a mixture of both RAT and RABR indicated that the two antisera blocked different types of attachment. The inhibitory activity of RAT on conjugate formation could be removed by absorption with B-lymphoma cells but not with myeloma cells. Analysis of the correlation between the inhibitory effect of RAT on cell-mediated lysis (CML) and on conjugate formation revealed that the serum was about twice as effective in its capacity to inhibit CML as to inhibit the attachment of PEL to target cells. The results indicate that while RABR inhibits non-specific attachment of CTL which does not lead to cell lysis. RAT exerts its effect by interfering with immunologically specific functional receptors on CTL.

Animals↗