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)

One hundred five trauma patients admitted to three trauma centers with injury Severity Scores of 20 or greater had lymphocyte phenotypic subsets characterized throughout their hospital course. Total lymphocytes, pan-T (CD2), helper T (CD4), suppressor T (CD8), pan B (CD20), and DR expressing lymphocytes were quantitated by monoclonal antibodies and flow cytometric analysis. Results were analyzed between three patient groups: uninfected, uneventful recovery (n = 64); major infection (n = 26); and dead (n = 15; 7 with sepsis). A significant lymphopenia, maximal at 3 days, occurred in the first postinjury week compared with controls (p < 0.05), which recovered over the study period. A hierarchical distribution was found between the three outcome groups with the lowest numbers of several lymphocyte phenotypes in those who died. T helper and suppressor cells were similarly affected, but lowest in patients destined to develop infection or die. The helper-suppressor ratio, however, was similar in all three outcome groups. Therefore, modulation early after injury aimed at restoring these subsets may reduce the risk of subsequent infection.
J Trauma 1993 Dec
PMID:Lymphocyte subset responses to trauma and sepsis. 826 80

We used time point studies to document the progression of neoplasms, haematologic abnormalities and associated lesions induced by Moloney murine sarcoma virus-349 (MoMuSV-349). BALB/c mice inoculated intraperitoneally with MoMuSV-349 first developed histologically discernible lesions at 14 days post-inoculation (d.p.i.). The initial neoplasms were characterized by whorls of fusiform or spindle-shaped cells enmeshing dense infiltrates of neutrophils and macrophages. By 21 d.p.i., clinical signs associated with MoMuSV-349 infection were evident. The distribution of the neoplasms was more widespread, although the histologic appearance of the tumours was very similar to that found at 14 d.p.i. All mice sacrificed at 28 d.p.i. exhibited characteristic clinical signs associated with MoMuSV-349, including moderate cachexia. Histologically, neoplasms observed at 28 d.p.i. contained a significant vascular component. By 35 d.p.i., all mice exhibited severe clinical signs (e.g. cachexia, dull hair coat, uneven gait). Histologically, all the neoplasms had a predominant vascular component. Non-neoplastic lesions, such as severe thymic atrophy and multifocal pulmonary haemorrhage, were commonly present. Mice sacrificed 42 d.p.i. were clinically, grossly and histologically similar to those sacrificed at 35 d.p.i. However, one difference found in the 42 d.p.i. group was the presence of rare rhabdomyosarcomas infiltrating the skeletal muscles. Mice inoculated with MoMuSV-349 developed severe neutrophilia and lymphopenia, and moderate anaemia. This study demonstrates that MoMuSV-349 induced angiosarcomatous neoplasms are characterized by stage development and severe haematologic and non-neoplastic abnormalities.
Int J Exp Pathol 1993 Dec
PMID:A temporal study of the lesions induced by MoMuSV-349. 829 54

The spontaneously diabetic BB rat is a well-established animal model of human insulin-dependent diabetes mellitus. Besides the lymphopenia gene (Iddm 1) and the MHC class-II genes of the RT1u haplotype (Iddm 2), at least one other non-MHC gene (Iddm 3) is considered essential for diabetes development. To investigate the participation of this third gene in the development of diabetes in our BB/OK rat subline, we analysed 119 [(BB/OK x DA)F1 x BB/OK] first backcross hybrids phenotypically and genotypically. Genotyping with 5 classical and 28 polymorphic microsatellite markers indicated that the third gene is located on chromosome 18, about 22 +/- 7 cM distal from the Olf locus (Iod score = 2.33). Significantly more diabetics than Iddm 1 and Iddm 2 homozygous nondiabetic subjects were homozygous for this locus. Interacting genes located on chromosomes X and/or 1 seem to be involved.
Diabete Metab 1995 Dec
PMID:Locus on chromosome 18 cosegregates with diabetes in the BB/OK rat subline. 858 50

The clinical data of a thirty-nine old inpatient woman are reported, whose main complaints were non-operable vulvo-vaginal condylomata, recurrent bacterial infections, complicated chickenpox and prominent lymphopenia. The peculiar facies get us to suggest the diagnosis of a case of the Di George syndrome in an adult patient. Was probably the associated neutropenia congenital and combined with immunodeficiency syndrome?
Recenti Prog Med 1995 Dec
PMID:[Di George's syndrome with neutropenia in an adult patient]. 858 82

More immunosuppressive drugs than ever have recently graduated from the laboratory to extensive clinical trials of their safety and efficacy in transplant patients. None of these drugs is perfect, but they control different forms of rejection in stringent animal models more effectively than other immunosuppressants, and these novel molecules suppress the immune system far more specifically than steroids and regimens that cause lymphopenia. Cyclosporin A and FK506 are the only drugs that selectively inhibit T-cell proliferation by blocking cytokine synthesis. The primary action of rapamycin appears to be 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, mycophenolate mofetil, brequinar sodium, and leflunomide. 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 of brequinar and deoxyspergualin. On the basis of preclinical studies, these drugs may effectively suppress clinical rejection that is acute (all), chronic (rapamycin, leflunomide, mycophenolate mofetil), or antibody mediated (brequinar, deoxyspergualin, mycophenolate mofetil, rapamycin, leflunomide). Some drugs (FK506, deoxyspergualin, mycophenolate mofetil, rapamycin, leflunomide) may reverse acute rejection refractory to conventional immunosuppression. Not only do these new drugs 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 will be more effective, less nephrotoxic, less myelotoxic, and less broadly immunosuppressive than current regimens based on cyclosporine, T-cell depletion, steroids, and azathioprine.
Ther Drug Monit 1995 Dec
PMID:Mechanisms of action of new immunosuppressive drugs. 858 21

This study sought to evaluate the prognostic value of clinical and laboratory parameters on survival in human immunodeficiency virus (HIV) seropositive and HIV seronegative patients with extrapulmonary tuberculosis (TB) from Tanzania. Over an 8-month period 192 consecutive patients with extrapulmonary TB, admitted to a major referral center in Tanzania, were enrolled in the study. Their symptoms, signs, and PPD skin test results were noted. Their sera were tested for HIV and analyzed for beta-2-microglobulin content. Univariate risk factors for 12 months' survival after the start of anti-TB chemotherapy were entered into a stepwise Cox regression model. Survival probabilities were estimated according to the number of risk factors. Of the 192 patients, 126 (65.6%) were HIV-infected, and 29.7% had disseminated TB. 35 patients, of whom 24 (68.6%) were HIV-positive, withdrew from the study immediately after hospital discharge. For survival analysis 157 patients remained. Within 12 months' follow-up after initiation of anti-TB therapy, the case fatality rate of the 102 HIV-infected patients was 22% and of the 55 HIV seronegative patients 2% (p 0.001). In the HIV seropositive patients the following independent risk factors were significantly associated with a decreased probability of survival: peripheral lymphadenopathy (Hazard Rate Ratio [HRR] 5.2, 95% confidence interval [CI] 1.7-16.2), a decreased activity score (bedridden 50%/day) (HRR 4.5, 95% CI 1.7-11.7), lymphopenia of 1000/mcl (HRR 4.4, 95% CI 1.7-11.8), and mycobacteremia (HRR 4.0, 95% CI 1.2-13.1). An anergic PPD skin test reaction proved to be another independent risk factor when the analysis was performed on 89 patients with available Mantoux test results. In the HIV seropositive patients, the 12 months' survival probabilities were 93%, 86%, 54%, and 0% for the presence of 0, 1, 2, and 2 risk factors respectively. The conclusion is that estimation of survival probabilities in patients with extrapulmonary TB may be possible without performing CD4 cell counts. (author's modified)
Tuber Lung Dis 1995 Dec
PMID:Predictive markers of survival in HIV-seropositive and HIV-seronegative Tanzanian patients with extrapulmonary tuberculosis. 859 71

Autoimmune conditions such as systemic lupus erythematosus (SLE) are sometimes associated with thymoma. Recently we drew attention to the development of SLE some months or even years following surgical thymectomy or thymomectomy. We now describe the first patient who developed SLE after chemotherapy and radiotherapy alone for malignant thymoma. A 38-yr-old female presented with an anterior mediastinal mass, which was found to be a malignant thymoma. Chemotherapy and radiotherapy were performed with complete resolution of the tumour. She remained stable for 4 yr, but then developed polyarthritis, lymphopenia, high titre anti-dsDNA antibody and antinuclear antibody. The diagnosis of SLE was established 44 months after malignant thymoma was treated. We believe that cases as this highlight the relationship between the thymus and the development of SLE.
Br J Rheumatol 1995 Dec
PMID:Development of systemic lupus erythematosus after chemotherapy and radiotherapy for malignant thymoma. 860 62

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.
Proc Natl Acad Sci U S A 1995 Dec 19
PMID:Improved biodistribution, tumor targeting, and reduced immunogenicity in mice with a gamma 4 variant of Campath-1H. 861 27

Membrane cofactor protein (MCP, CD46) of the complement system is a measles virus (MV) receptor. Human lymphocytes express a heavily glycosylated (H) and a lightly glycosylated (L) form of MCP, which confers a two-band profile on SDS-PAGE the ratio of which is controlled genetically and organ-specifically. In contrast, granulocytes express a single heavily glycosylated form regardless of lymphocyte MCP phenotype. We investigated susceptibility to MV of granulocytes and lymphocytes from individuals with different lymphocyte MCP phenotypes. In any individual, granulocytes were > 10-fold less susceptible to MV than lymphocytes, and the lymphocytes with predominant H form were generally less susceptible to those with an increasing amount of L form. Thus, lymphocytes always exhibit high susceptibility to MV compared to granulocytes in all individuals. This finding may explain the lymphopenia and immunosuppression observed secondary to MV infection.
Immunol Lett 1995 Dec
PMID:Human lymphocytes are more susceptible to measles virus than granulocytes, which is attributable to the phenotypic differences of their membrane cofactor protein (CD46). 871 5

Holstein calves given three consecutive i.m. injections of dexamethasone (DEX) (0.04 mg kg-1) showed lymphopenia and neutrophilia with increased numbers of mature neutrophils on post-injection Days 1 and 2, but these values returned to normal levels by post-injection Day 3. Interleukin-2 receptor (IL-2R) expression by peripheral blood mononuclear cells (PBMC) was evaluated by flow cytometry using a monoclonal antibody specific for bovine IL-2R alpha. Treatment with DEX significantly decreased expression of IL-2R alpha in Concanavalin A (Con A)-activated PBMC on Day 1 (P < 0.02) and on Day 2 (P < 0.1). On Day 3, expression of IL-2R alpha by PBMC was similar in control and DEX-treated calves. This decrease in IL-2R alpha expression correlated with decreased proliferative responses of PBMC to the T-cell mitogens, phytohemagglutinin (PHA) and Con A. Following in vitro treatment with recombinant human (rhu) interleukin-12 (IL-12) Con A-induced proliferative responses of PBMC tended to be higher in both groups. However, the rhu IL-12 induced increase of Con A activated proliferative responses were significantly greater in DEX-treated calves than in control calves. IL-2R alpha expression by PBMC was found to be less in calves transported 800 km in a truck as compared to that in PBMC from controls. These data suggest that stress-induced immunosuppression in calves may involve decreased IL-2R alpha expression and decreased IL-12 production. Serum chemistry results indicated a trend toward higher creatine kinase (CK) levels in DEX-treated calves. This may be due to the lysis of corticosteroid sensitive lymphocytes.
Vet Immunol Immunopathol 1995 Dec
PMID:Effect of stress on interleukin-2 receptor expression by bovine mononuclear leukocytes. 874 98


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