Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a case of methionine synthase deficiency associated with cellular immune deficiency discovered in a 14-year-old boy. Principal findings were: developmental delay, recurrent upper and lower respiratory tract infections, megaloblastic anemia, discovered at 3 months of age, unresponsive to cyanocobalamin and poorly responsive to folinic acid. Biochemical studies showed: an abnormal deoxyuridine suppression test despite normal serum folate, cobalamin and transcobalamin levels; a normal intracellular uptake of these two coenzymes; and an absolute requirement of methionine for fibroblast growth, suggestive of defective methionine synthesis. An absence of methionine synthase activity in the patient's bone marrow and a profound depression of this activity in lymphocytes and liver were found. Hypergammaglobulinemia with variable lymphopenia, depressed lymphocyte transformation after lectin or recall-antigen stimulation, defective delayed-type hypersensitivity and decreased natural killer activity were noted as well. The patient died at the age of 14.
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PMID:Megaloblastic anemia and immune abnormalities in a patient with methionine synthase deficiency. 342 20

Radiolabeled antibodies have shown promise for the treatment of lymphoma and for solid tumor targeting. Campath-1H is a humanized monoclonal antibody that reacts with the CD52 antigen present on human lymphoid and myeloid cells. Campath-1H is a gamma1 (G1) isotype that induces lymphopenia via an Fc-mediated mechanism(s). Isotype switches were engineered, and the resulting antibodies were expressed in NS0 mouse myeloma cells and biosynthetically radiolabeled with [35S]methionine. The forms included G1, G4, and a G4 variant that contained alanine substitutions at (EU numbering) Leu-235, Gly-237, and Glu-318. All isotypes bound antigen equivalently as assessed by target cell binding in vitro. The G4 variant had a greatly reduced capacity to interact with Fc receptor by virtue of reduced binding to THP-1 human myeloid cells and by a 1000-fold increase in EC50 to intermediate antibody-dependent cellular cytotoxicity. The pharmacokinetics of the isotypes were compared in CD-1 (nu/nu) mice bearing an experimental antigen-expressing tumor. The plasma half-life and tumor uptake were increased for the G4 variant. The G4 variant showed significantly less spleen, liver, and bone uptake but similar uptake in the lung, kidney, and stomach and lower tissue-to-blood ratios. Immunogenicity was assessed after repeated monthly administrations of unlabeled antibody in BALB/c mice. A 50% reduction in the incidence of anti-globulin response was observed for the G4 variant. These properties suggest that antibodies with reduced Fc receptor interaction merit additional study as potential targeting vehicles relative to other isotypes for radioimmunotherapy or situations where diminished normal tissue binding contributes to efficacy.
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PMID:Improved biodistribution, tumor targeting, and reduced immunogenicity in mice with a gamma 4 variant of Campath-1H. 861 27

In vitro effect of idebenone on human lymphocytes isolated from old and young donors was determined. The effects of drug were the same with the old and young donors cells. At concentrations of 2 microg/ml (6 microM) or less in the culture medium, idebenone showed no effect on phytohemagglutinin (PHA)-induced proliferation and protein synthesis, or on cell viability measured by Trypan Blue exclusion. Concentrations of 25 and 50 microg/ml showed dose-dependent suppression of the proliferation and protein synthesis which was associated with significant cytotoxicity. At concentrations of 8-10 microg/ml the compound appears to have just detectable effect on lymphocyte viability or ability to respond to PHA stimulation. It seems clear that such in vivo concentrations which would be associated with lymphopenia and immunologic suppression are not achieved with therapeutic doses of idebenone. The pattern of protein bands observed on fluorograms of sodium dodecyl sulfate-polyacrylamide gels of cells incubated with [(3)H]leucine and [(35)S]methionine was similar in control and idebenone-treated samples, consistent with a slight, nonspecific inhibitory effect on protein synthesis in cultures with higher doses of the compound. At these concentrations, idebenone induced a slight, but detectable, enhancement of the intracellular stress proteins, HSP70 and HSP90.
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PMID:Effects of idebenone on mitogen-induced proliferation of human lymphocytes. 1537 79