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Biomedical subjects

M Schlesinger

Publications and source records attributed to M Schlesinger.

At least 217 records · Page 12Linked to original sources

A multicenter study of outcome in systemic lupus erythematosus. I. Entry variables as predictors of prognosis.

A retrospective study of factors influencing survival in 1,103 patients with systemic lupus erythematosus (SLE) was carried out at 9 university centers diverse in geographic, socioeconomic, and racial characteristics. The mortality and disease characteristics of the patients at study entry varied widely among centers. The survival rates from the time patients with a diagnosis of SLE were first evaluated at the participating center was 90% at 1 year, 77% at 5 years, and 71% at 10 years. Patients with a serum creatinine greater than 3 mg/dl at study entry had the lowest survival rates: 48%, 29%, and 12% at 1, 5, and 10 years, respectively. Survival rate also correlated independently with the entry hematocrit, degree of proteinuria, number of preliminary American Rheumatism Association criteria for SLE satisfied, and source of funding of medical care. When data were corrected for socioeconomic status, race/ethnic origin did not significantly influence survival. Survival rates varied widely at different participating institutions, generally due to differences in disease severity. Place of treatment was independently associated with survival only in the second year after study entry. Disease duration before study entry did not account for the differences in disease severity.

Academic Medical Centers↗

A multicenter study of outcome in systemic lupus erythematosus. II. Causes of death.

Causes of death were examined for 1,103 systemic lupus erythematosus patients who were followed from 1965 to 1978 at 9 centers that participated in the Lupus Survival Study Group. A total of 222 patients (20%) died. Lupus-related organ system involvement (mainly active nephritis) and infection were the most frequent primary causes of death. Causes of death were similar throughout the followup period. Hemodialysis had little impact on the length of survival for patients with nephritis. Active central nervous system disease and myocardial infarction were infrequent causes of death. There were no deaths from malignancy.

Academic Medical Centers↗

The antigens of the chick blastula: a comparison between the epiblast, primary hypoblast, yolk entoderm, and extraembryonic yolk by immunoprecipitation in agar.

Antisera to chicken embryo epiblast, primary hypoblast, extraembryonic yolk, and yolk entoderm were elicited in rabbits. Extracts from the different sources were tested for their immunoprecipitation by these antisera in immunoelectrophoresis and double diffusion in agar (Ouchterlony) tests. The main findings were as follows: 1) Antigens recovered in the soluble fractions of the cells of the full hypoblast stage (Eyal-Giladi and Kochav, Stage XIII) are immunologically identical to antigens from the extraembryonic yolk, 2) Similar patterns of precipitation lines were formed between the soluble fractions of both the epiblast and primary hypoblast, and the different antisera. The epiblast and the primary hypoblast differed in 1-2 precipitation lines only, 3) The most prominent antigenic differences between the primary hypoblast and the epiblast reside in the microsomal fraction as revealed by immunoelectrophoresis, and 4) For all four sources of antigens which were compared, it was found that the electrophoretic mobility of the antigens migrating closest to the catodic end is modified according to the ratio of solvent to solute during the preparation of the lyophilized antigen.

Animals↗

Production of transcobalamin II by various murine and human cells in culture.

The ability of various murine and human cell types to secrete in vitro transcobalamin II (TCII), the vitamin B12 transport protein, was investigated. All cell types tested were found to secrete into the culture medium biologically active TCII molecules, capable of facilitating B12 uptake. The largest amounts of TCII were produced by primary cultures of murine fibroblasts and macrophages. Large quantities of TCII were also secreted by myeloma, erythroid leukemia, and macrophage-like tumor cell lines. Murine thymus cells of T lymphocyte tumors secreted only small quantities of TCII. Mouse monocytes and fibroblasts secreted considerably larger quantities of TCII than did their human counterparts. The data indicate that many cell types have the potential to produce biologically active TCII in vitro. Whether this in vitro potential also reflects in vivo biosynthetic activity is discussed.

Animals↗

Antibodies to human T lymphocytes in xenoantisera elicited with a new immature T-cell line (Peer).

Peer, a continuous line of immature T lymphocytes, was recently established from a patient with T-cell leukemia. In the present study antisera elicited in rabbits by immunization with Peer cells and absorbed with B cells were found to react with a distinct T-lymphocyte antigen. Absorbed anti-Peer serum was highly cytotoxic for human thymus cells and exerted a preferential activity on peripheral T lymphocytes. Peripheral blood lymphocytes (PBL) surviving exposure to anti-Peer serum and complement were depleted of most of the cells forming E rosettes, whereas the proportion forming EAC' rosettes was increased. Similarly, the depletion of cells forming E rosettes resulted in a concomitant reduction of the sensitivity of PBL to the cytotoxic effect of anti-Peer serum, while the enrichment of E-rosette forming cells had the opposite effect. Anti-Peer serum did not inhibit the formation of E rosettes by PBL in the absence of complement. Absorbed anti-Peer serum failed to exert any cytotoxic effect not only on normal B lymphocytes but also on the CBL and IMB B-cell lines, yet maintained a cytotoxic activity on the Raji and Daudi cell lines. A possible interpretation of these results is that immunization with Peer cells, a line of immature T lymphocytes, leads to the production of antibodies to a distinct antigen expressed on thymus and peripheral T cells. The antigen seems to be absent from normal peripheral B lymphocytes, but may be expressed on a line of pre-B cells, such as the Raji and Daudi lines.

Absorption↗

Establishment and characterization of a new leukaemic T-cell line (Peer) with an unusual phenotype.

We report the isolation and establishment in continuous culture of a human lymphoid cell line (Peer) from a case of T-leukemia. The Peer cell line lacks some typical cell-surface properties of T cells, namely sheep erythrocyte rosette formation and reactivity with two anti-T-cell sera, but has focal acid phosphatase and does express two other T-cell antigens, one defined by a monoclonal antibody, the other related to a T-cell subset (TH2). The cells are negative for B-cell markers (SmIg or cytoplasmic mu Fcgamma and C3 receptors, mouse erythrocyte rosettes) and EBV (EBNA). In addition, the Peer cell does not possess the typical phenotypic markers of "non-B, non-T" leukemia: cALL and Ia-like antigens, and the cytoplasmic hexosaminidase isoenzyme I, but is positive for terminal deoxynucleotidyl transferase by enzymatic and immunofluorescent criteria. The cell line requires exogenous L-asparagine for adequate growth in culture, a property known to be characteristic of certain T cells but not of B cells. The Peer cell line appears to have a maturation arrest at a developmental stage intermediate between the cortical thymocyte and a mature T-cell subset and to have lost some T-cell differentiation features.

Antigens, Neoplasm↗

Inhibition of cell-mediated lysis by xenoantibodies reactive with effector T lymphocytes.

The aim of the present study was to determine whether rabbit antisera against various murine tissue antigens contain antibodies that affect the activity of cytotoxic T lymphocytes in the absence of complement. Following heat inactivation, the xenoantisera were absorbed with mouse liver and kidney and tested for their capacity to inhibit cell-mediated lysis (CML). In the presence of complement (C), rabbit anti-brain antiserum (RABr), rabbit anti-thymus antiserum (RAT) and rabbit anti-boiled thymus antiserum (RABT) lysed effector T cells, and CML was abolished. In the absence of C, RAT maintained its strong inhibitory activity on CML, RABr had no inhibitory effect, whereas only some batches of RABT were effective. Monovalent Fab fragments of RAT inhibited CML as effectively as intact antibody molecules. The activity of RAT could be removed by absorption with T and B lymphocytes of various sources. Inhibitory antibodies could be removed by absorption with C3 H B lymphoma cells and upon elution from antibody-coated cells proved again highly effective in inhibiting CML. These results show that RAT contains antibodies which react with determinants shared by T and B lymphocytes and which block the activity of cytotoxic T cells.

Animals↗

Inhibition of the activity of cytotoxic murine T lymphocytes by antibodies to idiotypic determinants.

The nature of the receptors on the surface of cytotoxic T lymphocytes (CTL), which enable these cells to recognize antigens on allogeneic targets, is still a matter of controversy. In the present study various mouse alloantisera were tested for their capacity to inhibit, in the absence of complement, the cytotoxic activity of sensitized peritoneal T lymphocytes. The only antiserum which, even after heat inactivation, consistently inhibited cytotoxic T lymphocytes was an antiserum elicited in (C3H X C57B1/6)F1 mice by immunization with AKR/Cum thymus cells. The serum inhibited the cytotoxic reaction of either AKR/J or AKR/Cum CTL on EL-4 target cells but had no inhibitory activity on the cytotoxic reaction of AKR/J cells against P-815 target cells. Thus the inhibitory activity of the serum could not be attributed to antibodies against Ly-3 determinants present in the serum. This conclusion was strengthened by the finding that the inhibitory activity of the serum could be removed by absorption, not only with AKR/J thymus cells but also with AKR/J bone-marrow cells, a procedure which did not affect the titre of Ly-3 antibodies. The serum failed to exert any inhibition on cytotoxic T lymphocytes of BALB/c and C3H mice reacting against EL-4 target cells, indicating that the inhibitory activity of the antiserum did not result from contamination by antibodies against C57B1 antigenic determinants. It was concluded that the inhibitory activity of the antiserum resulted from the presence of antibodies against idiotypic determinants expressed on AKR/Cum thymus cells reacting against the hybrid hosts. It seems, therefore, that idiotypic determinants expressed on the surface of cytotoxic T lymphocytes may be directly involved in their cytotoxic activity.

Absorption↗

[Type V hyperlipemia. 54 cases (author's transl)].

Type V hyperlipemia is not very common. The series of 54 cases descrubed here is the largest reported to date. Our observations were recorded when lipidograms showed the presence of chylomicrons and a large pre-beta-lipoprotein spot in the serum of fasting subjects. Type V hyperlipemia was often combined with other metabolic syndromes such as diabetes, hyperuricemia or gout, or obesity. Chronic alcoholism was also noted in half our subjects, in whom hyperlipemia quickly regressed after alcohol consumption ceased. Ischemic arterial complications, chiefly coronary, were found in one third of our cases, and the vascular risks accompanying this type of hyperlipemia rose considerably in patients with high blood pressure. Various type of treatment were administered, but all subjects were put on a special diet, comprising either the elimination of alcoholic drinks only, or, in addition to this, reduced carbohydrate or calorie intake. As a rule, these measures resulted in a distinct regression of lipid anomalies. Clofibrate or derivatives proved effective in cases where hyperlipemia failed to respond to dietary measures.

Adolescent↗

The clinical significance of Raynaud's phenomenon in systemic lupus erythematosus.

In a prospective study of 226 patients with systemic lupus erythematosus (SLE), 91 patients (40%) had Raynaud's phenomenon. These patients were compared to 135 patients without Raynaud's phenomenon. Patients with Raynaud's phenomenon had a greater incidence of arthritis (P less than 0.02), malar rash (P less than 0.003), and photosensitivity (P less than 0.03), and a lesser incidence of severe renal disease as manifested by serum creatinine over 3.0 mg/dl (P less than 0.007) or creatinine clearance below 60 ml/minute. Patients with Raynaud's phenomenon were less likely to have severe, life threatening disease and received a lower average monthly (P less than 0.01) and a lower peak daily corticosteroid dose (P less than 0.01). Fourteen patients (16%) with Raynaud's phenomenon died, compared to 41 without (30%) (P less than 0.03). Raynaud's phenomenon in patients with SLE is associated with milder disease and may be regarded as a favorable prognostic sign.

Adrenal Cortex Hormones↗