Biomedical subjects

I Schulman

Publications and source records attributed to I Schulman.

At least 19 recordsLinked to original sources

PubMed1991

Centromeres: an integrated protein/DNA complex required for chromosome movement.

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Amino Acid Sequence↗

PubMed1986

Role of the Escherichia coli glnALG operon in regulation of ammonium transport.

Escherichia coli expresses a specific ammonium (methylammonium) transport system (Amt) when cultured with glutamate or glutamine as the nitrogen source. Over 95% of this Amt activity is repressed by growth of wild-type cells on media containing ammonia. The control of Amt expression was studied with strains containing specific mutations in the glnALG operon. GlnA- (glutamine synthetase deficient) mutants, which contain polar mutations on glnL and glnG genes and therefore have the Reg- phenotype (fail to turn on nitrogen-regulated operons such as histidase), expressed less than 10% of the Amt activity observed for the parental strain. Similarly, low levels of Amt were found in GlnG mutants having the GlnA+ Reg- phenotype. However, GlnA- RegC mutants (a phenotype constitutive for histidase) contained over 70% of the parental Amt activity. At steady-state levels, GlnA- RegC mutants accumulated chemically unaltered [14C]methylammonium against a 60- to 80-fold concentration gradient, whereas the labeled substrate was trapped within parental cells as gamma-glutamylmethylamide. GlnL Reg- mutants (normal glutamine synthetase regulation) had less than 4% of the Amt activity observed for the parental strain. However, the Amt activity of GlnL RegC mutants was slightly higher than that of the parental strain and was not repressed during growth of cells in media containing ammonia. These findings demonstrate that glutamine synthetase is not required for Amt in E. coli. The loss of Amt in certain GlnA- strains is due to polar effects on glnL and glnG genes, whose products are involved in expression of nitrogen-regulated genes, including that for Amt.

Ammonia↗

PubMed1985

Treatment of acute idiopathic thrombocytopenia of childhood with intravenous infusions of gammaglobulin.

Gammaglobulin treatment was given at a dose of 1 gm/kg/day intravenously in 29 patients with acute idiopathic thrombocytopenic purpura: 15 previously untreated, 10 resistant to steroids, and four who were steroid dependent. The average platelet increase in 24 hours was greater than 50,000/microliter; the average peak platelet count was 194,000/microliter. Eighteen of 25 patients required only one infusion; 10 of these 18 never required any additional (maintenance) therapy. Outcome in previously untreated and steroid-resistant patients was identical; however, previously untreated patients required only 1.8 gm/kg total dose of gammaglobulin, whereas steroid-resistant patients received 3.9 gm/kg. Only one steroid-dependent child of the 29 patients still requires maintenance therapy, at 6-week intervals. Toxicity was minimal. Cost was minimized by not admitting patients and by giving treatment in one visit, rather than five.

Acute Disease↗

PubMed1985

Elevation of platelet associated antibody levels in patients with chronic idiopathic thrombocytopenic purpura expressing the B8 and/or DR3 allotypes.

The HLA type DR3 was present in 11 of 26 patients with Chronic Idiopathic Thrombocytopenic Purpura (ITP), a significantly increased frequency (p less than 0.05). Levels of platelet associated immunoglobulin M(PAIgM) were significantly higher in the B8 and/or DR3 positive group of chronic ITP patients than in the B8 DR3 negative patients despite similar clinical outcomes. Other immunologic parameters assessed, including serum immunoglobulin levels, rate of catabolism of transfused IgG, and antibody coated autologous red cell clearances were similar for both groups. These results suggest that there is an immunobiologic abnormality associated with the B8 DR3 allotypes which may result in a predisposition not only to chronic ITP, but also to a significant increase in PAIgM. These results are in accord with studies linking autoantibody with B8 DR3.

Adolescent↗

PubMed1983

Intravenous use of gammaglobulin in the treatment of chronic immune thrombocytopenic purpura as a means to defer splenectomy.

Intravenous gammaglobulin was used to treat 12 children with chronic immune thrombocytopenic purpura in order to avoid splenectomy. The average rise in platelet count with initial treatment was 226,000/microliters. Currently, one patient is in remission, four patients maintain platelet counts greater than 40,000/microliters without treatment, four patients maintain platelet counts greater than 40,000/microliters with single maintenance infusions of IV IgG at four- or 10-week intervals; three patients did not respond to treatment. In nine of 12 patients, splenectomy was avoided or at least postponed. In responding patients, we were able to discontinue immunosuppressive medication. Platelet count rises with initial IV IgG therapy were correlated with both platelet antibody levels and with a better long-term outcome. Toxicity was minimal.

Adolescent↗

PubMed1983

Platelet-associated immunoglobulin G in childhood idiopathic thrombocytopenic purpura.

Platelet-associated IgG was studied in children with acute and chronic ITP and in patients with thrombocytopenic SLE, using the microtiter solid-phase radioimmunoassay. Of the children with acute ITP, 85% had elevated PAIgG levels. The degree of elevation of PAIgG at onset of disease did not correlate with the development of chronicity. Of the children with acute ITP, clinically and hematologically indistinguishable from the rest, 15% had normal PAIgG values. All of 22 children with chronic ITP had elevated PAIgG values. Although there was good correlation between the platelet count and the PAIgG value in children with chronic ITP, the association was not as striking in those with acute ITP; thus, factors in addition to the level of PAIgG may contribute to the thrombocytopenia in the latter group. Patients with SLE and thrombocytopenia had higher values of PAIgG than would be predicted from the platelet count; the PAIgG value is probably not the only factor determining the degree of immune thrombocytopenia.

Acute Disease↗

PubMed1983

Intravenous gammaglobulin treatment of chronic idiopathic thrombocytopenic purpura.

High-dose intravenous gammaglobulin (IVIgG) was given to 12 children and adults with chronic idiopathic thrombocytopenic purpura (ITP) to avoid splenectomy or because they either failed to respond to or required maintenance with high doses of steroids and/or immunosuppressives. The average platelet count increase to initial therapy was 239,500/microliters (range 23,000-790,000). A concomitant IgG Fc receptor blockade, measured by IgG-sensitized 51Cr-labeled autologous erythrocytes, was seen in 11 of 11 patients tested, both splenectomized and not splenectomized, lasting 3-4 wk. Six or more months after treatment, 2 children are in remission, 2 children and 2 adults are stable requiring no therapy with platelet counts of approximately 50,000 and 30,000, respectively, 3 children require maintenance IVIgG therapy at 2-10-wk intervals, and 1 child and 2 adults have become refractory to further IVIgG. Splenectomy was not performed in 4 children. Two adults were able to discontinue daily prednisone. The 3 patients who became unresponsive to Swiss Red Cross gamma-globulin (IgSRK) therapy did so in conjunction with a markedly elevated platelet-associated IgG and IgM. Serum IgM increased an average of 103 mg/dl after the IVIgG infusions. No significant side effects were seen.

Adolescent↗

PubMed1983

A microtiter solid-phase radioimmunoassay for platelet-associated immunoglobulin G.

An MSPRIA is described for measuring platelet-associated immunoglobulins by competitive inhibition of the binding of radiolabeled goat anti-human class-specific antibody to solid-phase immunoglobulins. PAIgG can be estimated from calibration curves constructed from soluble IgG inhibitors. The MSPRIA for IgG is antibody class-specific. The coefficient of variability is between 6% and 20%. The MSPRIA is more sensitive than other described assays. Comparative studies demonstrated that ACD-A is the preferred anticoagulant for collecting platelets for the MSPRIA and that sonicated platelets are more reliable than intact platelets in demonstrating elevated PAIgG in immune thrombocytopenias. Intact platelets from 18 normal volunteers had PAIgG ranging from 0.4 to 3.3 fg/platelet (mean +/- S.D. = 1.5 +/- 1). The same platelets when sonicated had a mean +/- S.D. PAIgG of 3.3 +/- 1 fg/platelet, with a range of 1 to 5. Only 60% of 30 adult ITP patients with presumed immune thrombocytopenia had elevated PAIgG levels when their intact platelets were studied. When these same platelets were sonicated, 87% of them had abnormal levels of PAIgG.

Antibody Specificity↗

PubMed1977

Platelet-associated IgG in immune thrombocytopenic purpura.

A method for the measurement of immunoglobulin G associated with gel-filtered platelets is described and finding in 70 control subjects and 37 patients with immune thrombocytopenic purpura (ITP) are reported. Control platelet-associated IgG (PAIgG) levels (nanograms IgG per 10(9) platelets) averaged (+/-SD) 1231+/-424; samples studied after 24 and 48 hr remained within the control range. PAIgG values of 19 adult and 12 childhood patients with chronic ITP averaged 4711+/-3025 and 4923+/-3955, respectively, and differed significantly from controls (p less than 0.001). There was an inverse correlation between PAIgG values and the chronic ITP patient's platelet count. Six patients with childhood acute ITP had PAIgG levels ranging from 5588 to 56,250 and appeared to represent a different statistical population from those with chronic ITP. In chronic ITP patients responding to splenectomy, there was an immediate normalization of PAIgG levels; however, a certain percentage of patients studied several months after splenectomy evidenced elevated PAIgG levels in association with normal platelet counts. These data showed that the direct measurement of platelet associated antibody is a useful technique in the diagnosis and follow-up of patients with chronic ITP. Preliminary studies in patients with acute ITP have suggested that this method may be useful in differentiating acute and chronic childhood ITP.

Adult↗

PubMed1975