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D Senitzer

Publications and source records attributed to D Senitzer.

At least 37 records · Page 2Linked to original sources
PubMed1988

Possible genetic predisposition to idiopathic focal segmental glomerulosclerosis.

HLA-A, B, and DR antigen frequencies were studied in a group of 57 patients to determine possible inborn susceptibility to idiopathic focal segmental glomerulosclerosis (FSGS). There were 34 white patients and 23 black patients, most of whom had nephrotic syndrome and later developed renal failure. HLA-DR4 was significantly increased in both patient groups when compared with their respective control groups. This association has not been previously reported. Of note, the association with DR4 was most striking in patients with adult onset disease (in blacks, relative risk equals 5.2; in whites, relative risk equals 5.8). No other antigen was increased in both patient groups but HLA-A28 was increased in blacks. These data support the notion of genetic predisposition to focal segmental glomerulosclerosis in two different ethnic groups.

Adolescent↗
PubMed1988

HLA associations in heroin-associated nephropathy.

Heroin-associated nephropathy (HAN) occurs almost exclusively in black heroin abusers, suggesting a genetic link to the disease. To further study this possibility, the frequencies of HLA-A, B, C, and DR antigens were determined in a group of 47 black patients with HAN. Included in the analyses is a subgroup of 16 patients with biopsy-proven focal glomerulosclerosis. Patient frequencies were compared with three separate control populations, the first a normal black population from New York City, the second from a national registry, and the third a group of blacks with idiopathic focal glomerulosclerosis. Only the frequency of HLA-BW53 was consistently increased significantly in the patients as compared with the control groups. This finding supports the notion that a genetic predisposition may exist in the addicted population for the development of renal disease.

Adult↗
PubMed1987

Ethylnitrosourea-induced transplacental carcinogenesis in the mouse: tumor response, DNA binding, and adduct formation.

We have confirmed previous results which suggest that transplacental exposure of fetal mice to carcinogens does not cause an increase in tumor incidence as they mature unless treatment occurs after midorganogenesis. In C3HeB/FeJ mice we found a negligible increase in tumor incidence and multiplicity following transplacental exposure to the direct-acting carcinogen ethylnitrosourea (ENU) on gestation day 10, but significant increases in lung and liver tumor incidence following exposure on days 13 or 15 or in adults. To explore the possibility that this observed difference is due to differences in the biodistribution of the carcinogen or its interaction with cellular macromolecules, the level of covalent binding between ENU and fetal and maternal DNA following an i.p. injection of a dose of 50 mg/kg of tritium-labeled ENU was measured 30 min after its injection into pregnant females on days 10, 13, and 15 of gestation. The DNA from fetal and maternal lung, liver, and brain was isolated and the amount of covalent binding estimated from the dpm/mg DNA recovered. Samples of DNA were hydrolyzed and chromatographed to determine that the bound tritium was associated with ENU-DNA adducts and not as a product of DNA synthesis. The level of binding of ENU to fetal DNA was equivalent at all gestation days studied but was significantly less than maternal tissues. Binding to the DNA of maternal liver was 4-fold greater than to fetal DNA while maternal lung and brain DNA were bound at intermediate levels. We conclude that the lack of carcinogenic response to ENU documented here, in fetal mice exposed early in gestation (day 10), is not due to differences in ENU binding to fetal DNA during development.

Adenoma↗
PubMed1987

Inhibition of neutrophil shape change by an inhibitor of chemotaxis.

Human mononuclear cells exposed to staphylococcal peptidoglycan in serum-free culture rapidly produce an inhibitor of neutrophil chemotaxis which we have previously described. We found that this inhibitor of chemotaxis has its most potent effect on the inhibition of neutrophil shape change from a spherical to a polarized configuration. In order to quantify this shape change inhibition, we developed an assay using flow cytometric techniques. Neutrophils exposed to a chemoattractant simultaneously change their shape and decrease their forward angle light scattering intensity (delta FLS) with a correlation coefficient of 0.886 (p less than 0.001). In 51 experiments, neutrophils pretreated with the inhibitor of chemotaxis decreased their FLS by only 6.8 +/- 1.3 channels, while neutrophils pretreated with medium or control culture supernatants decreased theirs by 26.4 +/- 1.9 and 20.5 +/- 3.0 channels respectively (p less than 0.001). The factor which causes inhibition of shape change was indistinguishable from the inhibitor of chemotaxis by physical properties and chromatography. We conclude that this inhibitor of chemotaxis may act by inhibiting a physiologic step at or before shape change.

Chemical Phenomena↗
PubMed1987

Recurrent membranoproliferative glomerulonephritis type 1 in successive renal transplants.

We report a man who developed renal failure due to membranoproliferative glomerulonephritis (MPGN) type 1 which recurred in two cadaveric kidney transplants. This is the third such case in the literature. Nephrotic syndrome developed within 1 month following transplantation and histologic evidence of disease recurrence was documented in both kidneys 2 months after transplantation. Both grafts failed within 18 months. Factors which determine disease recurrence remain obscure.

Adult↗
PubMed1986

Isolation of B lymphocytes for HLA-DR typing using monoclonal antibodies.

Isolating sufficient B cells for DR typing is often a problem, particularly in patients with low lymphocyte and/or B cell counts. This paper describes a simple method for preparing highly purified B cells using monoclonal antibodies and complement to kill the majority of non-B cells. Mononuclear cells are isolated by standard Ficoll-Hypaque techniques and incubated at 0 degrees C for 10 min with the following monoclonal antibodies: OKT3 (pan T cell), OKT11 (pan T and null cell), and Leu11b (NK cell). Rabbit complement is added and the mixture is incubated at 37 degrees C for 20 min. Dead cells are then removed by Percoll gradient centrifugation. This procedure results in cell preparations containing 90.1 +/- 1.3% B cells as measured by two-colow immunofluorescence with an Epics C flow cytometer. A yield of 52% can routinely be obtained. In contrast, nylon wool adherence results in preparations with only 44 +/- 9.1% B cells with a yield of 31%. B cells prepared by the monoclonal antibody procedure always show stronger and clearer reactions on DR typing trays. These results are consistent with the flow cytometric analyses of the B cell preparations. In summary, this procedure has the following advantages: increased accuracy of DR typing, decreased sample size (only 1.0 X 10(7) mononuclear cells are required), reduced time of cell preparation, and reduction in the number of repeat typings necessitated by poor yields and/or results.

Antibodies, Monoclonal↗
PubMed1985

Infectious antecedent of immunoblastic lymphoma. Progressive immunosuppression in a patient with lymphogranuloma venereum.

Angioimmunoblastic lymphadenopathy is a nonmalignant disease of unknown etiology often progressing to immunoblastic lymphoma. Immunologic deficiency is evident in these patients as well as in those with various infections found in association with the acquired immune deficiency syndrome (AIDS). This report describes a previously healthy young woman in whom angioimmunoblastic lymphadenopathy developed in association with lymphogranuloma venereum, with progressive loss of immunologic competence. This deterioration paralleled the evolution of angioimmunoblastic lymphadenopathy into a rapidly fatal immunoblastic lymphoma.

Adult↗
PubMed1984

Protein A-binding immunosuppressive mouse serum factors.

In this study protein A of Staphylococcus aureus has been used to isolate an immunosuppressive component present in mouse serum. The suppressive effect of mouse serum on lymphocyte activation was partially abrogated by prior adsorption on protein A, and also by ammonium sulfate precipitation or specific immune precipitation with anti-IgG but not with anti-IgM. Protein A-binding material was isolated after chromatography on protein A-Sepharose and studied in spleen cell cultures. Protein A eluates from normal or NZB/NZW mice were found to suppress concanavalin A (Con A)-activated normal mouse spleen cells, and suppression was more potent with NZB/NZW serum isolates. Suppressive activity was dependent upon the dose of eluate added to cell cultures. The suppressive effect of NZB/NZW protein A-binding material was apparent in both Con A- and lipopolysaccharide (LPS)-stimulated normal mouse spleen cells, and required early addition to the cell cultures or preincubation with target lymphocytes. The suppressive activity was not detectably cytotoxic during a suppressive preincubation period. The possible relevance of these observations to experimental strategies in tumor immunotherapy is discussed.

Animals↗
PubMed1984

The induction of anti-erythrocyte antibodies in vivo by administration of lipopolysaccharide.

Experiments were designed to determine whether B-cell activation of control mouse strains with lipopolysaccharide (LPS) could induce the same anti-erythrocyte antibody responses observed to occur spontaneously in the NZB strain. When BALB/c and DBA/2 mice were injected intraperitoneally with 100 micrograms of LPS, antibodies to X, HB, and HOL antigens could be detected 2 weeks later at levels comparable to those found spontaneously in NZB mice. Injection of C3H/HeJ mice, nonresponders to LPS, resulted in no detectable anti-erythrocyte antibody responses. When NZB mice were treated with LPS in this way, serum levels of anti-RBC antibodies increased. A measure of the percentage hemolysis induced by sera from these animals in the presence of an exogenous complement source revealed a higher incidence and hemolytic titer in LPS-injected BALB/c and DBA/2 strains than in PBS-injected mice. In addition, injection of LPS induced the appearance of erythrocyte-bound IgM and IgG in BALB/c, DBA/2, and NZB mice. These data suggest that LPS-induced B-cell activation results in the appearance of anti-erythrocyte antibodies.

Animals↗
PubMed1983

Splenocytes from NZB mice exhibit spontaneously high rates of fusion compared to control strains.

A previous report (G. E. Woloschak and D. Senitzer, submitted for publication) has demonstrated that mitogen-stimulated splenocytes fuse at a much higher frequency than untreated splenocytes as measured by the fusion index (a calculation of the number of nuclei in fused cells vs the total number of nuclei). A measurement of the fusion indices of NZB spleen cells provides results markedly different from those observed with splenocytes from control strains of mice--NZB spleen cells exhibit a spontaneously high fusion index. In this assay, they spontaneously display the same fusing capacity as that observed in cultures of mitogen-treated spleen cells from control strains of mice. This elevated fusion index is not affected by treatment with anti-Thy-1.2 and complement, but is abrogated by treatment with anti-immunoglobulin serum and complement. This suggests that a B cell is responsible for the high fusion index of NZB splenocytes. This high fusion index is present when using splenocytes from both male and female mice in the fusion assay, and can be observed using spleen cells from NZB mice as young as 12 days. This appears to be the result of a spontaneous B-cell activation in NZB mice.

Aging↗
PubMed1983

T lymphocyte abnormalities in disseminated histoplasmosis.

Disseminated histoplasmosis is associated with depression of T cell-mediated immunity and in some cases anergy. In this report, two patients with disseminated disease are described. Both had a depression of T cell-mediated immunity as well as other abnormalities of immune response. In one, a patient with relapse, a marked depression in the ratio of T helper to T suppressor cells was noted. Neither patient had any predisposing condition known to be associated with disseminated disease.

Adult↗
PubMed1983

Effect of mitogenic stimulation of murine splenocytes on PEG-induced cell fusion.

A cell fusion assay system was devised as a means of measuring cell activation. Polyethylene glycol (PEG) was used to induce fusion between spleen cells of various mouse strains and the BW5147 thymoma cell line. A fusion index (FI) was calculated by determining the ratio of the number of nuclei in fused cells to the number of nuclei in all cells and multiplying by 100 (the FI could range from 0 to 100). Spleen cells from BALB/c mice were compared in PEG-induced fusion assays. BALB/c spleen cells stimulated with phytohemagglutinin, leucoagglutinin, concanavalin A, pokeweed mitogen and LPS showed FI two- to three-fold higher than those found in unstimulated cultures, indicating that stimulated cells fuse at much higher rates. This response is mitogen dose-dependent and parallels DNA synthesis as measured by 3H-TdR incorporation. Treatment of spleen cells with cycloheximide 12 h prior to fusion had no effect on FI. In vivo and in vitro stimulation of BALB/c, C57BL/6 and NZW mice with LPS resulted in enhanced FI. This was not the case in low-responder DBA/2 and nonresponder C3H/HeJ animals.

Animals↗
PubMed1982

Suppression of murine T-cell mitogenesis by metabolic products of arachidonic acid.

We examined the ability of arachidonic acid (AA) to inhibit mitogen stimulation of mouse splenic lymphocytes. Dose related suppression of [3H]-thymidine incorporation by cells stimulated with either phytohemagglutinin or concanavalin A occurred at concentrations of AA above 1 microgram/ml. AA-induced suppression required that AA be added to cultures within 6 hours of the addition of mitogen. Addition of AA at 24 hours resulted in diminished suppression, while delaying addition of AA until 48 hours had no effect on mitogen stimulation. Preincubation with AA did not alter mitogen stimulation when cells were washed free of AA. The addition of indomethacin or mefanamic acid to the cultures significantly reversed AA-induced suppression. Inhibitors of the lipoxygenase pathway or thromboxane synthesis had no effect, while an inhibitor of both thromboxane and prostacyclin synthesis partially prevented AA-induced suppression only at the highest concentration of AA. Removal of adherent cells resulted in a diminished capacity for AA to suppress mitogenesis and to stimulate PGE2 synthesis.

Animals↗
PubMed1980

Purification and characterization of mammary myoepithelial and secretory cells from the lactating rat.

Myoepithelial and secretory cells from the mammary gland of the lactating rat have been isolated, purified, and characterized. Mammary tissue was dissociated with collagenase into basket-like networks of myoepithelial cells and single secretory cells. Because of their larger size, the myoepithelial cell networks could be separated from other mammary and blood cells by differential centrifugation. Isolated secretory cells were purified by isopycnic centrifugation in 25% bovine serum albumin. The purified myoepithelial and secretory cells were viable, as shown by the incorporation of 32P into distinct macromolecules that were separable by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Both myoepithelial and secretory cells retained their characteristic morphology after isolation and purification, as shown by light, transmission, and scanning electron microscopies. The isolated myoepithelial cells were unique and, thus, distinguishable from other mammary cells in a number of respects; they 1) contracted in response to the addition of oxytocin, 2) bound [3H]oxytocin specifically, 3) accounted for the content of alkaline phosphatase and [Na+ + K+]ATPase in mammary tissue, and 4) reacted specifically with antiserum prepared against purified myoepithelial cells. The purified secretory cells were unique in possessing glucose-6-phosphate dehydrogenase activity. The different cell markers not only gave independent estimates of the purity of the cell fractions, but they also may be helpful in identifying mammary cells in stages of differentiation and neoplastic transformation.

Adenosine Triphosphatases↗
PubMed1980

Prostaglandin E1 therapy of murine chronic serum sickness.

We studied the effect of PGE1 in pharmacologic doses on immune complex-induced glomerulonephritis produced by daily intraperitoneal injections of apoferritin. Mice received one of the following injection schedules: apoferritin 4 mg/day, apoferritin 4 mg/day plus PGE1 200 microgram twice daily, saline, or PGE1 200 microgram twice daily. Administration of apoferritin alone resulted in mesangial cell proliferation in all 14 mice with crescent formation in nine. Evidence of subepithelial and mesangial immune complex deposition and a significant increase in urine protein excretion was found. Treatment with PGE1 resulted in a mild increase in mesangial cells in six of 14 mice. No mice developed crescents on this regimen. In addition, proteinuria was prevented, and there was a marked diminution of immune complex deposition. Antiapoferritin antibody was detected in the sera of mice from both groups. No alteration in lymphocyte response to mitogen or in vitro PGE1 suppression of blastogenesis was detected. Our results indicate that PGE1 therapy alters immune complex glomerulonephritis in this model of murine chronic serum sickness by reducing glomerular immune complex deposition. However, no difference in specific or nonspecific immunologic responses was detected.

Animals↗