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)

Serum and CSF from 32 patients with idiopathic ALS, 30 age-matched controls and 30 MS patients were investigated regarding immunoglobulin concentration and virus-specific antibodies, the lymphocytes in the peripheral blood and lymphocyte subsets were also investigated. ALS patients' results were compared with findings in MS and controls. The ALS patients had significantly higher IgG concentration in serum than the controls, marked lymphopenia, reduction of CD2, CD8 and Leu 7 positive cells and increase of the CD4/CD8 ratio and of SIg-positive lymphocytes. Compared with the MS patients, the ALS patients showed similarity in T-subset distribution with a lower standard deviation. No HTLV-I and HIV antibodies were found in any group and no significant differences in antibody distribution to Toxoplasma G, herpes simplex, cytomegalovirus, measles and mumps viruses were evident. All ALS patients were investigated at an early disease stage, therefore, our findings seem to support the conclusion that the immune alterations are related to the mechanisms of the disease and not to complications of its evolution.
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PMID:Immunity assessment in the early stages of amyotrophic lateral sclerosis: a study of virus antibodies and lymphocyte subsets. 326 63

The effect of hysterectomy was studied on natural killer (NK) cell activity, the distribution of lymphocyte subpopulations, and the endocrine stress response in 16 patients allocated to receive extradural analgesia S5-T4 (group I) or neuroleptanaesthesia (NLA) (group II). In group II a significant decrease in NK cell activity was found after operation for at least 3 days, while surgery during extradural analgesia did not induce significant changes. The impaired NK cell activity was accompanied by leucocytosis and lymphopenia affecting the T-lymphocytes (OKT3+ and OKT4+), the B-lymphocytes (B1+) and NK cells (Leu 11+). Compared with group II, extradural analgesia significantly reduced the cortisol and noradrenaline response to surgery, while the adrenaline response in both groups was abolished. The results suggest that the decrease in NK cell activity and alterations in lymphocyte subsets induced by surgery and general anaesthesia can be prevented to a certain degree by extradural analgesia.
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PMID:Influence of extradural and general anaesthesia on natural killer cell activity and lymphocyte subpopulations in patients undergoing hysterectomy. 337 25

The effects of elective coronary artery bypass grafting (CABG) and the associated endocrine stress response on natural killer (NK) cell activity in peripheral blood, the distribution of lymphocyte subpopulations, and the phytohemagglutinin (PHA)-induced lymphocyte transformation were studied in 20 patients anesthetized with either etomidate-high dose fentanyl (75-125 micrograms . kg-1) or midazolam-low dose fentanyl (less than 20 micrograms . kg-1). The endocrine response to surgery was measured as changes in serum cortisol, plasma epinephrine, and norepinephrine. Compared with control values, a significant increase of NK cell activity was found in both groups prior to induction of anesthesia, followed by a decrease after induction until initiation of cardiopulmonary bypass (CPB) and a gradual increase to levels exceeding controls during CPB. Postoperatively, NK cell activity and the lymphocyte transformation to PHA stimulation were significantly depressed for at least 1-3 days. These changes were accompanied by severe lymphopenia affecting the T-lymphocytes (T3, T4, and T8) and the NK cells (Leu 11). Apart from a delayed cortisol increase in the etomidate group, the endocrine response showed a similar pattern in the two groups. Compared with control values, a significant decrease in the serum cortisol until CPB could be demonstrated, followed by a significant increase persisting for at least 6 days postoperatively. The plasma catecholamines showed a steep rise and, consequently, a significant increase during CPB, followed by a gradual return to control values in the postoperative period. The results indicate that, in patients undergoing CABG, immune surveillance is impaired prior to CPB and during the early postoperative period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Natural killer cell activity and lymphocyte function during and after coronary artery bypass grafting in relation to the endocrine stress response. 349 99

Lymphocyte subpopulations in vitro in 13 patients with bacteriologically-proven tuberculosis and 12 matched controls, by immunofluorescence using monoclonal antibodies have been studied. Active tuberculosis was associated with significant reductions in absolute numbers of total T (Leu 4 or 1+), T4 (Leu 3a+) and B (Leu 12+) lymphocytes, but there were no significant differences in total T8 (Leu 2a+) counts. In two patients, T4-lymphopenia was sufficiently profound to cause reversal of T4: T8 ratio (less than 1.2). These changes were not related to the radiological extent of the disease or size of the Mantoux reaction. Normal ranges for the different classes of lymphocytes were readily restored by chemotherapy.
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PMID:T4 lymphopenia in human tuberculosis. 350 79

Twenty patients with intractable rheumatoid arthritis were treated with 750-rad or 2,000-rad lymphoid irradiation in a randomized double-blind comparative study. Over a 12-month followup period, there was a significant improvement in 4 of 7 and 6 of 7 standard parameters of disease activity following treatment with 750 rads and 2,000 rads, respectively. Transient, short-term toxicity was less frequent with the lower dose. In both groups, there was a sustained peripheral blood lymphopenia, a selective depletion of T helper (Leu-3a+) lymphocytes, and reduced in vitro mitogen responses. These changes did not occur, however, in synovial fluid. These results suggest that 750-rad lymphoid irradiation is as effective as, but less toxic than, that with 2,000 rads in the management of patients with intractable rheumatoid arthritis.
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PMID:Lymphoid irradiation in intractable rheumatoid arthritis. A double-blind, randomized study comparing 750-rad treatment with 2,000-rad treatment. 394 14

Using monoclonal antibodies in conjunction with flow cytometry, circulating lymphocyte subsets with distinct functions in the regulation of the immune response were enumerated in 32 patients with proven renal carcinoma. Analyses were performed at presentation and sequentially during the clinical course of the patients. Untreated patients with advanced disease had a deficit of T cells with the "helper/inducer" phenotype (Leu-3a+) and this resulted in abnormal T "helper/suppressor" (Leu-3a+/Leu-2a+) ratios. Following nephrectomy, performed in 26 patients, there was a significant increase in the number of T cells with the "helper/inducer" phenotype and a significant increase in T "H/S" ratios. Subsequent follow-up at a minimum of 2 months after nephrectomy showed that the increase in T cells with the "helper/inducer" phenotype was maintained (with the exception of 6 patients with disease progression) and was then accompanied by a significant increase of the T cell subset with the "suppressor/cytotoxic" phenotype (Leu-2a+). Pre-operative renal arterial embolisation resulted in an early transient lymphopenia. The response to embolisation combined with nephrectomy was little different when compared with nephrectomy alone. These observations represent a novel view of the immunosuppressive effects of renal carcinoma and their relation to anaemia and disease progression are discussed.
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PMID:Lymphocyte subsets in renal carcinoma--a sequential study using monoclonal antibodies. 623 43

Sarcoidosis is a multisystem disease characterized by enhanced immune responses at sites of involvement. For this reason, an immunohistological study using monoclonal antibodies against T-cell subpopulations was carried out in order to evaluate the topographic distribution of immunocompetent cells in tissue sections obtained from a variety of involved organs, such as parenchymal lung, lymph nodes, eyes, skin, and liver. Biopsy specimens were also stained for detection of immunoglobulins, complement, and fibrinogen deposits. The data demonstrate a redistribution of T cells from the blood to all the sites of disease activity where they account for the large majority of infiltrating cells, both in the early lesions (merely a lymphocytic infiltrate) and in well-organized granulomas. Moreover, these cells express a helper-related phenotype, as demonstrated by the high Leu-3/Leu-2 ratios, at sites of involvement with respect to the blood (blood, 1.8/1; transbronchial lung biopsies, 10.5/1; lymph nodes, 19/1; skin, 28/1; liver, 22/1; eye, 14/1). In line with this helper infiltration is the presence of plasma cells and immunoglobulin deposits, suggesting a local hyperreactivity of the B-cell immune system. Both the hypergammaglobulinemia and the T lymphopenia usually observed in the blood of sarcoid patients could be explained by these observations. Comparative analysis of immunohistological data and bronchoalveolar lavage (BAL) findings provides further evidence that BAL cellularity reflects the changes already occurring in lung histology. The studies emphasize the importance that immunological phenomena play in the pathogenesis of sarcoidosis and provide new insights into the mechanisms leading to the formation and maintenance of the sarcoid granuloma.
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PMID:Immunohistological study in sarcoidosis: evaluation at different sites of disease activity. 636 83

The immune status of 34 breast cancer patients was investigated by measuring several parameters of peripheral blood lymphocytes--monoclonal antibodies against T cell (Leu-1) and B cell (HLA-DR) antigens, and against cytotoxic/suppressor (Leu-2a) and helper/inducer T cells (Leu-3a); E rosette formation as a T cell marker and surface Ig as a B cell marker; FcIgG receptor expression; and mitogen responsiveness of the peripheral blood lymphocytes to PHA, Con A, and PWM. Most of the patients had normal percentages of B and T cells and T cell subsets but there was a trend to lower percentages of T cells and their subsets in stage IV patients. Due to lymphopenia in stages I and IV and in patients which had received radio- or chemotherapy, the total number of B and T cells and T cell subsets was less in these groups than in the controls. The percentage of FcIgG positive cells was higher in these groups than in controls and therefore the absolute number remained unchanged. In general, a decrease in T cells seems to be indicative of a poor prognosis. Mitogen responsiveness does not have prognostic significance since a patient in stage III, in good general health, had a low mitogenic response and a terminal stage IV patient had a normal mitogenic response.
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PMID:Study of B and T lymphocyte surface markers in breast cancer patients using anti-B and anti-T cell monoclonal antibodies. 661 Aug 35

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

The oncogenic protein Vav harbours a complex array of structural motifs, including leucine-rich, Dbl-homology, pleckstrin-homology, zinc-finger, SH2 and SH3 domains. Upon stimulation by antigens or mitogens, Vav becomes phosphorylated on key tyrosine residues and associates with other signalling proteins, including the mitogen receptors Zap-70 (ref. 6), Vap-1 (ref. 5) and Slp-76 (ref. 7). Disruption of the vav locus by homologous recombination causes severe defects in signalling by primary antigen receptors, leading to abnormal lymphocyte proliferation and lymphopenia. Despite the importance of Vav cell signalling, the function of this protein remains unknown. Here we show that tyrosine-phosphorylated Vav, but not the non-phosphorylated protein, catalyses GDP/GTP exchange on Rac-1, a protein implicated in cell proliferation and cytoskeletal organization, causing this GTPase to switch from its inactive to its active state. Transfection experiments also show that phosphorylation of Vav on tyrosine residues leads to nucleotide exchange on Rac-1 in vivo and stimulates c-Jun kinase, a downstream element in the signalling pathway involving this GTPase. Our results have identified a function for Vav and define a mechanism in which engaged membrane receptors activate its signalling pathway.
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PMID:Phosphotyrosine-dependent activation of Rac-1 GDP/GTP exchange by the vav proto-oncogene product. 899 Jan 21


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