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

A 60-year-old white man presented with a syndrome of fever, polyarthritis, pleurisy, and lymphopenia, and had a positive antinuclear antibody test (after 5 months of quinidine therapy). Quinidine-induced antinuclear autoantibodies were of the IgM and IgG classes and were directed mainly to nuclear histones, predominantly histones H1 and H2B. Antibodies to native DNA and nonhistone nuclear antigens were not seen during the patient's clinical course. Upon withdrawal of quinidine therapy, the patient had prompt improvement of clinical symptoms followed by a gradual resolution of serologic abnormalities.
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PMID:Quinidine-induced lupus erythematosus. 637 64

Spontaneous DNA synthesis (SDS) in tonsillar lymphocytes was investigated in 58 cases by [3H]-thymidine incorporation under a certain culture condition without any mitogens. Tonsillar lymphocytes showed an extremely higher uptake of [3H]thymidine than peripheral blood lymphocytes. Cells exhibiting SDS were mainly B cells, but, however, they needed the helper functions of T cells and glass-adherent cells to synthesize DNA. SDS in tonsillar lymphocytes decreased with age and was lowest in the 21-30 year age group. SDS in cases with complications such as chronic sinusitis, nasal allergy or secretory otitis media was significantly higher than that in cases with no complications.
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PMID:Spontaneous DNA synthesis in tonsillar lymphocytes and its clinical implications. 661 48

Dietary exposure to 1000 ppm of supplemental Zn did not result in grossly observable Zn toxicity or Zn-induced Cu deficiency in adult mink. These same concentrations did, however, produce achromatrichia, alopecia, lymphopenia and a reduced rate of growth in the offspring produced by the Zn-treated females. These mink kits also exhibited profound immunosuppression. The in vitro blastogenic response of peripheral blood lymphocytes to concanavalin A was significantly (P less than 0.001) lower in kits born to Zn-treated dams than the response of those born to control dams. The depressed immunoresponsiveness was not a permanent defect since a normal lymphocyte response was seen approximately 14 weeks after weaning and being placed on an unsupplemented basal diet. The impaired lymphocyte reactivity is believed to be the result of altered DNA synthesis in these cells and/or an inhibition of macrophage functions necessary for normal response to the mitogen concanavalin A.
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PMID:Effects of excessive dietary zinc on the intrauterine and postnatal development of mink. 668 75

Staphylococcal enterotoxin A (SEA) administration to monkeys produced an initial lymphocytic leukopenia lasting approximately 24 h. Lymphocytes isolated from blood circulation (PBL) during this stage had normal or decreased [3H]thymidine incorporating activity. After 48 h, however, a significant increase (five- to sixfold) in [3H]thymidine incorporating activity into PBL was apparent. The peak of incorporating activity (seven- to eightfold) was reached 3 to 4 days after SEA administration, followed by a gradual decline, reaching the baseline after 2 weeks. The increased levels of [3H] thymidine incorporation in PBL were concomitant with the conversion of lymphopenia into lymphocytosis, accompanied by the release of many immature cells into the circulation. Lymphocytes isolated 24 h after SEA administration in vivo did not respond to the mitogenic action of SEA in vitro. Lymphocytes isolated at later stages after SEA challenge were fully activated by toxin. From a series of studies, it was concluded that SEA administered to monkeys caused, during the initial 24 h, the removal of a great proportion of lymphocytes from the circulation, followed by the release of new immature cells with augmented DNA synthesis activity. The lymphocytic leukocytosis state declined gradually and reached normal levels between 3 and 4 weeks after the SEA challenge. The biological implications of the hematological changes occurring after SEA challenge in vivo are discussed.
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PMID:In vivo effect of staphylococcal enterotoxin A on peripheral blood lymphocytes. 671 41

The use of T cell subtyping to distinguish rheumatoid arthritis (RA) from systemic lupus erythematosus (SLE) was evaluated. We determined the distribution of IgG Fe receptor T cells (TG), IgM Fc receptor T cells (TM), and T cells lacking Fc receptors (Tnull) in 17 patients with RA and 7 patients with SLE. All RA patients including 3 antinuclear antibody positive-rheumatoid factor negative cases had normal numbers and percentages of TG, TM, and Tnull, whereas all SLE patients had a relative and absolute deficiency of TG. This TG lymphopenia was a better discriminator for SLE (7 of 7 SLE, 0 of 17 RA) than anti-DNA antibodies, hypocomplementemia, circulating immune complexes or total number of T cells.
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PMID:The use of T cell subtyping to distinguish rheumatoid arthritis from systemic lupus erythematosus. 697 81

The production of lymphoid cells in the pig spleen was studied autoradiographically after selective labeling of the spleen using an extracorporeal perfusion circuit. Tritiated thymidine was added as a DNA precursor. One to 4 days after local labeling of the spleen the relative and absolute number of spleen-derived lymphocytes were determined in the following organs: mesenteric, cervical and inguinal lymph nodes, thymus, bone marrow, Peyer's patches, tonsils, three different parts of the gut, lung, liver, and blood. The labeled lymphocytes which migrated to these organs were all small lymphocytes, except for some large cells in the lamina propria. In the bone marrow, however, a considerable number of the spleen-derived immigrants were transformed into plasma cells. The total number of labeled lymphocytes decreased dramatically from Day 1 to Day 4 after labeling, indicating a high percentage of short-lived cells. Within the spleen, plasma cells had the highest labeling index of about 30% at Day 1 but this dropped to only 1.5% on Day 3. The organ distribution of the splenic emigrants changed from Day 1 to Day 4 with a relative increase in lymphocytes found in lymph nodes and a decrease in the lung and intestinal wall. The newly formed splenic lymphocytes migrated to T-and B-cell areas in lymph nodes, Peyer's patches and tonsils. In the intestinal wall labeled lymphocytes were found in the lamina propria and also as intraepithelial lymphocytes. There was no obvious redistribution between organ compartments with time after labeling of the spleen. The spleen produces large numbers of lymphocytes, which show typical organ distribution and homing to areas in lymphoid and nonlymphoid organs.
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PMID:Organ distribution and fate of newly formed splenic lymphocytes in the pig. 705 22

One hundred twenty-seven biopsy specimens from clinically normal light-protected skin of 88 patients with active and inactive lupus erythematosus (LE) were examined for deposits of IgG, IgM, IgA, and C3 at the dermal-epidermal junction (DEJ). Deposits were found in 91% of those with active disease and in 33% of those with inactive disease. The finding of such deposits reflected active disease just as did a decrease in serum C3 and C4 levels, elevated anti-double-stranded DNA, the presence of LE cells, lymphopenia, and an elevation of the ESR. The presence or absence of deposits in repeated biopsy specimens indicated changing disease activity, as estimated clinically, just as did changes in the other variables mentioned. Neither immunoreactants in skin nor any other laboratory abnormality reflected renal disease or other type of organ involvement. Deposits of IgG were not more commonly found in patients with renal disease.
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PMID:The lupus band test as a measure of disease activity in systemic lupus erythematosus. 710 27

More immunosuppressive drugs than ever have recently graduated from the laboratory to extensive clinical trials of their safety and efficacy in patients undergoing transplantation. Although none of these drugs is perfect, they control different forms of rejection in stringent animal models more effectively than other immunosuppressants; yet these novel molecules suppress the immune system far more specifically than steroids and regimens that cause lymphopenia. Cyclosporin G and IMM 125 (analogues of cyclosporine) and FK506 are the only drugs that selectively inhibit T-cell proliferation by blocking cytokine synthesis. The primary action of rapamycin and leflunomide appears to be an inhibition of the actions of cytokines and growth factors on T, B, and some nonimmune cells. T and B cells are more sensitive than nonimmune cells to the depletion of purines and pyrimidines caused by mizoribine, mycophenolic acid, and brequinar sodium. Nucleotide depletion causes interruption of DNA synthesis and glycosylation of adhesion molecules in immune cells. Further differentiation of T and B cells after proliferation into fully functional immune cells is inhibited by unknown mechanisms by brequinar and deoxyspergualin. On the basis of preclinical studies, these drugs may effectively suppress clinical rejection that is (1) acute (all drugs), (2) chronic (rapamycin, leflunomide, and mycophenolic acid), or (3) antibody-mediated (brequinar, deoxyspergualin, mycophenolic acid, and rapamycin). Some drugs (FK506, deoxyspergualin, mycophenolic acid, rapamycin, and leflunomide) may reverse acute rejection refractory to conventional immunosuppression. These new drugs not only block different biochemical steps that normally lead to fully functional T and B cells after stimulation by alloantigen, but their toxicity profiles also differ. Results from preclinical studies predict that use of selected combinations of these drugs in patients will be more effective, less nephrotoxic, less myelotoxic, and less broadly immunosuppressive than current regimens based on cyclosporine, T-cell depletion, steroids, and azathioprine ... at least, that's the idea! Or as former Vice President Dan Quayle said, "It's a question of whether we're going to go forward into the future, or past to the back."
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PMID:New small molecule immunosuppressants for transplantation: review of essential concepts. 750 52

A putative retrovirus was isolated from a dog with a severe, acquired immunodeficiency-like syndrome. The haematological abnormalities and immunological deficiencies included anaemia, leucopenia (lymphopenia and neutropenia), thrombocytopenia, decreased humoral immunity, and ineffective T-cell responses in-vitro. The necropsy findings included generalized lymphoid depletion, severe bone marrow hypoplasia, plasmacytic infiltrates in lymphoid and non-lymphoid organs, and severe secondary infections. Supernates of peripheral blood mononuclear cell cultures from the affected dog contained an agent with manganese-dependent reverse transcriptase (RT) activity that sedimented at a density of 1.122 g/ml. RT activity was also found post-mortem in extracts prepared from the bone marrow, lymph nodes, and small intestine. The lymph nodes and small intestine expressed a 3.8 kb mRNA that was recognized by a bovine leukaemia virus (BLV) pol DNA probe by Northern blotting. DNA isolated from the lymph nodes and small intestine from the affected dog showed distinct band patterns by Southern analysis, suggesting an exogenous retrovirus. The retrovirus could be propagated in normal canine peripheral blood mononuclear cells or short-term canine lymphocyte cell lines in-vitro, and was cytopathogenic for cells of canine, but not human, origin. These results suggest the existence of a pathogenic canine retrovirus capable of producing disease of the type associated with retroviruses in other species.
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PMID:Retrovirus-like activity in an immunosuppressed dog: pathological and immunological findings. 753 63

The amount of [3H]thymidine incorporated into DNA in lymphocytes stimulated with Concanavalin-A increases exponentially with time at different concentrations of glutamine, reaches a peak value, then gradually decreases. When the value (log10 thymidine incorporation glutamine present -log10 thymidine incorporation glutamine absent) obtained from the exponential phase is plotted against time, a linear plot is obtained for each glutamine concentration. When these linear rates of incorporation are plotted against glutamine concentration, hyperbolic curves are obtained for different times of culture. The peak value of incorporation (which reflects the final number of cells which entered the cell cycle) is determined by the concentration of mitogen and occurs at an earlier time as the number of cells in culture is increased and as the concentration of glutamine is increased. These findings suggest that increasing the plasma glutamine concentration above the normal physiological level may be of value in increasing the proliferation of lymphocytes in conditions of lymphopenia. Adenosine, a fuel of purine nucleotide synthesis, which may affect the lymphoproliferative response also via specific adenosine receptors, increases the rate of incorporation of [3H]thymidine but this effect depends upon the concentration of glutamine; at low concentrations of glutamine, the stimulation by adenosine is apparent whereas at high concentrations of glutamine adenosine appeared to inhibit proliferation.
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PMID:The effects of cell number, concentrations of mitogen and glutamine and time of culture on [3H]thymidine incorporation into cervical lymph node lymphocytes stimulated by concanavalin-A. 755 69


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