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)

Lymphocytes must proliferate and differentiate in response to low concentrations of a vast array of antigens. The requirements of broad specificity and sensitivity conflict because the former is met by low-affinity antigen receptors, which precludes achieving the latter with high-affinity receptors. Coligation of the membrane protein CD19 with the antigen receptor of B lymphocytes decreased the threshold for antigen receptor-dependent stimulation by two orders of magnitude. B lymphocytes proliferated when approximately 100 antigen receptors per cell, 0.03 percent of the total, were coligated with CD19. The B cell resolves its dilemma by having an accessory protein that enables activation when few antigen receptors are occupied.
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PMID:CD19: lowering the threshold for antigen receptor stimulation of B lymphocytes. 137 18

A 23-year-old woman experienced six distinct episodes of severe combined neutropenia and thrombocytopenia. At least one of the episodes was accompanied by hemodialysis-requiring acute renal failure and fragmentation hemolysis (hemolytic uremic syndrome [HUS]). In retrospect, all episodes were probably associated with the ingestion of quinine. Quinine-dependent antibodies to platelets, neutrophils, T lymphocytes, and red blood cells (RBCs) were detected in the patient's serum. By a monoclonal antibody antigen capture assay, the patient's serum contained IgG antibodies, which in the presence, but not absence, of quinine reacted with platelet glycoprotein (GP) complexes Ib/IX and IIb/IIIa, but not Ia/IIa. By immunoprecipitation assay, the serum, after addition of quinine, reacted strongly with an 85-Kd neutrophil membrane protein and weakly with 130- and 60-Kd moieties. Serum adsorbed with RBCs in the presence of quinine continued to react with platelets and neutrophils, and serum that was absorbed with platelets continued to react with neutrophils and RBCs, indicating that the antigenic targets were different on platelets, neutrophils, and RBCs. Since platelets and endothelial cells share some antigens, we tested patient serum for antibodies to human umbilical vein endothelial cells (HUVEC); no quinine-dependent antibodies to HUVEC were detected. However, her quinine-dependent antibodies not only bound to platelets and neutrophils, but also activated neutrophils. Thus, the patient's serum with quinine aggregated neutrophils, but neither agent alone caused activation. Moreover, the patient's serum with quinine (but not without) augmented the adherence of neutrophils to HUVEC. Treatment of the patient's serum with staphylococcal protein A removed the quinine neutrophil aggregation cofactor, suggesting it was due to IgG. In both neutrophil aggregation and adherence assays, decomplementation of the patient's serum markedly blunted its effect. Furthermore, the patient's serum failed to aggregate formalin-inactivated neutrophils, suggesting neutrophil activation, probably by activated complement, was necessary for aggregation and adhesivity to endothelium. We conclude that our patient's neutropenia, thrombocytopenia, lymphopenia, and anemia were due to quinine-dependent antibodies, and that these antibodies recognized epitopes that were different in the three target cell populations. We further suggest that HUS was likely secondary to the activation and adhesion of neutrophils to endothelium.
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PMID:Characterization of multiple quinine-dependent antibodies in a patient with episodic hemolytic uremic syndrome and immune agranulocytosis. 161 Oct 88

RT6 is an unusual cell membrane protein that is expressed exclusively by postthymic T cells. The inherent defect in its expression has been correlated to lymphopenia and genetically determined susceptibility for insulin-dependent diabetes mellitus in the rat. We report here the primary structure of the RT6.2 alloantigen as deduced from the cDNA sequence. The predicted amino acid sequence of RT6.2 begins with a conventional leader of 20 amino acids and ends in a hydrophobic C-terminal extension peptide of 29 amino acids as is common for phosphatidylinositol-anchored proteins. Native RT6.2 is predicted to comprise 226 amino acids, with a calculated Mr of 26,036. Four cysteine residues account for two intrachain disulfide bonds. The sequence lacks potential N-glycosylation sites and contains an excess of positively charged residues. Homology searches in protein sequence data banks suggest that RT6.2 is not encoded by a member of the immunoglobulin supergene family. Moreover, these analyses did not reveal any close homologies of RT6.2 to known proteins: the highest homology found was 21.2% identity in a 52-amino acid overlap to the torpedo acetylcholinesterase precursor. Southern blot analyses indicate that RT6.2 is the product of a single-copy gene and provide evidence for closely related genes in the mouse and other species. The corresponding gene products remain to be identified.
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PMID:Primary structure of rat RT6.2, a nonglycosylated phosphatidylinositol-linked surface marker of postthymic T cells. 230 May 88

Fludarabine is a highly effective chemotherapeutic agent for chronic lymphocytic leukemia/small lymphocytic lymphoma and is also active in other B-cell lymphoproliferative disorders. Although highly efficacious in destroying the malignant B-cells, fludarabine also causes T-cell lymphopenia and immunosuppression. We present five patients given fludarabine for low-grade B-cell lymphoproliferative disorders who showed transformation of the primary neoplasm to a higher grade tumor. Immunohistologic antibody studies were performed on paraffin-embedded tissue sections of the initial tissue (when available) and on the follow-up biopsy specimens for CD20, CD3, CD45RO, CD43, CD30, CD15, and latent membrane protein (LMP-1) for Epstein-Barr virus (EBV). The initial diagnoses in these five patients included chronic lymphocytic leukemia/small lymphocytic lymphoma (three cases), follicle center lymphoma (one case), and Waldenstrom's macroglobulinemia (one case). All of the follow-up biopsy specimens showed scattered Hodgkin's-like cells, and two of the five also showed foci of large-cell transformation. The Hodgkin's-like cells showed CD30 immunoreactivity in four of the five cases and CD15 immunoreactivity in three of the five. Strong immunoreactivity of the large, atypical, Hodgkin's-like cells for LMP-1 of EBV was noted in four cases; in the remaining case, this finding was equivocal. In situ hybridization for EBV-encoded RNA was positive in four of the five cases. Molecular studies by polymerase chain reaction (PCR) showed the presence of EBV in three of the five cases. PCR for detection of immunoglobulin heavy chain demonstrated identical monoclonal rearrangements in the original lymphoma and transformation in one case with available material. The CD4 lymphocyte count in each patient was less than 550/microL, indicating cellular dysfunction. Transformation of low-grade non-Hodgkin's lymphomas after fludarabine therapy might be associated with EBV and severe immunosuppression.
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PMID:Detection of Epstein-Barr virus in transformations of low-grade B-cell lymphomas after fludarabine treatment. 938 67

The pro-oxidative properties of the four flavonoids, quercetin, morin, naringenin and hesperetin, in human lymphocyte system were investigated. Naringenin and hesperetin accelerated the oxidation of deoxyribose induced by Fe(3+)/H(2)O(2) in a concentration range of 0-200 microM, but quercetin and morin decreased it when the concentration was greater than 100 microM. The generation of hydrogen peroxide and the superoxide anion and the production of TBARS in lymphocytes were increased with increasing concentration of a flavonoid. Cell membrane protein thiols of the lymphocytes decreased when treated with the four flavonoids. Quercetin and hesperetin had no significant effect (p>0.05) on the activity of glutathione reductase, but morin and naringenin could inhibit the activity of the enzyme at a concentration of 200 microM, when compared to the control group. The glutathione S-transferase activity was slightly decreased by treatment with each of the four flavonoids only at a concentration of 200 microM. Therefore, the DNA damage in lymphocytes induced by the flavonoids in the model system might have been due to their stimulation of oxidative stress in the lymphocytes, which resulted in the decrease of cell membrane protein thiols, increase of lipid peroxidation in cell membrane and in the influence of the antioxidative enzyme activities.
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PMID:Pro-oxidative properties of flavonoids in human lymphocytes. 1284 45

In the HAX1/HtrA2-OMI/PARL (HOP) mitochondrial protein complex, anti-apoptotic signals are generated by cleavage and activation of the serine protease HtrA2/OMI by the rhomboid protease PARL upon recruitment of both proteases to inner mitochondrial membrane protein HAX1 (HS1-associated protein X-1). Here we report the negative regulation of the HOP complex by human leukemia-associated myeloid leukemia factor 1 (MLF1). We demonstrate that MLF1 physically and functionally associates with HAX1 and HtrA2. Increased interaction of MLF1 with HAX1 and HtrA2 displaces HtrA2 from the HOP complex and inhibits HtrA2 cleavage and activation, resulting in the apoptotic cell death. Conversely, over-expressed HAX1 neutralizes MLF1's effect and inhibits MLF1-induced apoptosis. Importantly, Mlf1 deletion reverses B- and T-cell lymphopenia and significantly ameliorates the progressive striatal and cerebellar neurodegeneration observed in Hax1-/- mice, with a doubling of the lifespan of Mlf1-/-/Hax1-/- animals compared to Hax1-/- animals. Collectively, these data indicate that MLF1 serves as a proapoptotic antagonist that interacts with the HOP mitochondrial complex to modulate cell survival.
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PMID:MLF1 is a proapoptotic antagonist of HOP complex-mediated survival. 2813 43