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)

Zinc deficiency alters lymphocyte and monocyte function in man and animals. A patient with isolated zinc deficiency was found to have lymphopenia (420 lymphocytes/microliter), depressed T-cell mitogen response (48% of normal control), increased numbers of circulating T-suppressor cells (OKT8 reactive cells) and decreased circulating T-helper cells (OKT4 reactive cells). Activity of the patient's natural killer (NK) cells was 1 lytic unit/10(6) cells (normal 10 to 40), and monocyte cytotoxicity (MC) was four times that of normal controls. Zinc repletion in vivo improved the peripheral lymphocyte count, corrected the abnormal OKT8-to-OKT4 ratio, normalized T-cell response to mitogen, improved NK function, and lowered MC to control values. A divalent cation chelator, 1,10-orthophenanthroline (OP), was used to simulate zinc deficiency in vitro. T-cells exposed to OP are nonresponsive to mitogen unless zinc is added. NK function of lymphocytes from normal donors exposed to OP was depressed in a time- and dose-dependent manner. NK activity of peripheral blood lymphocytes (PBL) from 12 normal donors exposed to 50 microM OP for 16 hr was 10.3 +/- 7 lytic units/10(6) cells (mean +/- S.E.M.) vs. 32.6 +/- 14 for cells incubated in medium alone. When monocytes were exposed for 16 hr to 50 microM OP, however, MC significantly increased to a range two to five times that of control. OP-induced alterations of lymphocyte and monocyte function was reversed by the addition of 50 microM zinc but not calcium or magnesium. Since NK activity and MC are thought to be important in host tumor immunity, alterations in zinc metabolism may have important implications for human tumor immune surveillance mechanisms.
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PMID:Alterations in human natural killer cell activity and monocyte cytotoxicity induced by zinc deficiency. 660 71

In our previous study of soft tissue infections in parenteral drug abusers, two thirds of the infections were polymicrobial. Oral and enteric organisms were frequently recovered. These patients and a group of uninfected addicts showed frequent cutaneous anergy, lymphopenia, and hypergammaglobulinemia. An additional group of uninfected addicts was studied. The mean levels of IgA, IgG, and IgM were higher in the uninfected addicts. In the addict and control groups, elevations in IgA (17 percent of total), IgG (65 percent), and IgM (19 percent) levels were found. Zinc levels were within normal limits. T-cell populations below 70 percent were seen in five of the seven addicts and two of the four control subjects. Reversed helper to suppressor cell ratios were found in three of the seven addicts and control subjects. No consistent pattern of immunologic abnormalities emerged. The interrelationship of the abnormalities in the addict and their relationship to AIDS is unclear.
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PMID:Infections in parenteral drug abusers. Further immunologic studies. 660 67

Flurbiprofen, a potent non-steroidal anti-inflammatory and antipyretic agent, was given as an intravenous infusion (2 mg/kg) followed by a bolus injection of 1 mg/kg six hours later. After drug administration body temperature and rumen contractions were slightly depressed, whereas urea values gradually increased; serum sorbitol dehydrogenase (SDH) activity, plasma iron concentration and the number of circulating lymphocytes were significantly lower. Intravenous injection of endotoxin from Escherichia coli O111B4 (0.1 microgram/kg) caused shivering, fever, inhibition of rumen contractions, changes in heart rate, lymphopenia, neutropenia followed by neutrophylic leucocytosis, changes in urea values, hypoferraemia, hypozincaemia and a decline in serum alkaline phosphatase (ALP) activity, whereas gamma-glutamyltranspeptidase, glutamic oxalacetic transaminase, lactic dehydrogenase and SDH values were not significantly altered. Pretreatment with flurbiprofen completely abolished the febrile reactions to endotoxin. The endotoxin-induced inhibition of rumen contractions was only delayed. The drug blocked the initial tachycardia to endotoxin but did not prevent the secondary biphasic increase in heart rate. Flurbiprofen failed to modify the endotoxin-induced decrease in both plasma zinc and serum ALP activity whereas the decline in plasma iron concentration was delayed. After drug pretreatment the changes in circulating white blood cells were more pronounced. These data demonstrate that most of the haematological, blood biochemical and clinical effects of endotoxin cannot be blocked by flurbiprofen, and that these effects are not due to the increase in body temperature alone. Tolerance induced by repetitive daily intravenous administration of endotoxin resulted in an almost complete abolition of all the effects. However, the plasma iron values from tolerant goats were significantly lower than those from non-tolerant animals, which demonstrates that the development of a refractory state can result in modification of this biochemical parameter.
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PMID:Endotoxin-induced fever and associated haematological and blood biochemical changes in the goat: the effect of repeated administration and the influence of flurbiprofen. 675 96

Though lymphopenia is often noted in malnourished humans and rodents, little is known about the effects of suboptimal nutriture on lymphopoietic processes. Focusing primarily on cells of the B lineage in the marrow of young adult mice, a moderate degree of zinc deficiency (MZD) caused a 43% decline in the proportion of nucleated cells bearing B220 with a 91% decline noted among more severely zinc deficient mice (SZD). Early B cells (B220+Ig-) were highly sensitive to the deficiency, being barely detectable in SZD mice and reduced by almost 60% in MZD mice. Immature B cells (B220+IgM+IgD-) were similarly affected, declining 35% to 80% depending on the degree of the deficiency. In MZD mice, mature B cells (IgM+IgD+) exhibited moderate losses, being somewhat resistant. A more profound loss in this population was noted for SZD mice. Flow cytometric (FACS) scatter profiles indicated that zinc deficiency caused a sharp decline in the proportion of small nucleated cells which in the marrow are thought to contain a high proportion of developing lymphoid cells. There was a concomitant increase in large granular cells that paralleled a substantial increase in the proportion of nucleated cells bearing Mac-1 for both MZD and SZD mice. Given the dramatic depletion of cells of the B lineage in the marrow created by a deficiency in zinc, it is probable that disruptions in lymphopoietic processes in the marrow play a key role in the resulting lymphopenia observed in many types of malnutrition.
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PMID:Depletion of cells of the B lineage in the bone marrow of zinc-deficient mice. 763 24

Thymic atrophy and lymphopenia are immunological hallmarks of many forms of malnutrition including deficiencies in zinc. Extreme thymic atrophy (70-80%) along with a 50% loss of splenocytes in mice maintained on a zinc deficient diet (ZD) for 30 days suggested that the deficiency might be altering lymphopoiesis or the production of new lymphocytes by the bone marrow. As shown herein, mice who were marginally zinc deficient being 72-75% the body weight of adequately fed controls, exhibited a 50% decline in pre B-cells and a 25% decline in immature B-cells. The mature B-cells of the marrow appeared fairly resistant to effects of suboptimal zinc intake. Interesting, this pattern was similar to results obtained by treating bone marrow cells with levels of glucocorticoids analogous to those found in nutritionally deficient rodents. Furthermore, these same concentrations of steroids were shown to induce significant levels of apoptosis or cell death among pre and immature B-cells which accounted for their declining numbers subsequent to exposure to glucocorticoid. In order to better ascertain the potential role of glucocorticoids generated during zinc deficiency on lymphopoietic processes, adrenalectomies were performed in an attempt to remove glucocorticoids from the equation. Subsequently, adrenalectomized and sham operated mice were placed on a ZD or zinc adequate diet (ZA). Levels of steroids at the time of sacrifice were elevated six fold in non-adrenalectomized ZD mice compared to ZD adrenalectomized mice. Removal of the adrenal gland protected the thymus of ZD mice from atrophy and also provided substantial protection of lymphopoietic processes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Possible roles for glucocorticoids and apoptosis in the suppression of lymphopoiesis during zinc deficiency: a review. 770 4

Autoantibodies to Ro/SSA occur in nearly half of the patients with systemic lupus erythematosus and are associated with lymphopenia, photosensitive dermatitis, and pulmonary and renal disease, which suggests that they have an immunopathologic role. The majority of Ro/SSA precipitin-positive patients produce serum antibodies that bind to the 60-kD and 52-kD Ro/SSA proteins. We previously isolated and determined the nucleotide sequence of a cDNA clone that encodes the 52-kD form of the human Ro/SSA protein. In the present study, we have determined the chromosomal location of the gene by in situ hybridization to the end of the short arm of chromosome 11. Hybridization of portions of the cDNA probe to restriction enzyme-digested DNA indicated the gene is composed of at least three exons. The exon encoding the putative zinc fingers of this protein was found to be distinct from that which encodes the leucine zipper. An RFLP of this gene was identified and is associated with the presence of lupus, primarily in black Americans.
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PMID:The mapping of the human 52-kD Ro/SSA autoantigen gene to human chromosome 11, and its polymorphisms. 809 96

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

The purpose of this study was to assess whether polymyxin B together with pentoxifylline, had beneficial effects on the acute-phase-response to E. coli endotoxin in the dwarf goat (n = 6). Polymyxin B partly neutralizes E. coli endotoxin by forming inactive polymyxin B-lipopolysaccharide (LPS) complexes; pentoxifylline has been reported to suppress the LPS-induced production of tumour necrosis factor (TNF-alpha). E. coli LPS (0.0067 microgram/kg/min over 30 min) induced fever, tachycardia, inhibition of rumen motility, a decline in WBC, lymphopenia, and decreases in plasma zinc and iron concentrations. Most of the haematological, blood biochemical and clinical effects of E. coli LPS were significantly reduced by polymyxin B pretreatment (0.1 mg/kg/min over 30 min, i.v.). Pentoxifylline (0.3 mg/kg/min over 30 min, i.v.) did not reduce the clinical and blood biochemical effects of E. coli LPS, however, it modulated the number of circulating neutrophils. No synergistic effects were observed after i.v. infusion of polymyxin B with pentoxifylline. The lack of synergy may be due to the production and release of pro-inflammatory cytokines other than TNF-alpha.
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PMID:Effects of pentoxifylline and polymyxin B on the acute-phase-response to Escherichia coli endotoxin in dwarf goats. 904 51

Severe weight loss in the absence of respiratory, enteric or systemic clinical disease or gross pathologic lesions is often observed when immunologically naive boars are placed in conventional health swine facilities. Affected animals develop this weight loss in spite of receiving pre-entry vaccinations against common swine pathogens, such as Haemophilus parasuis or Mycoplasma hyopneumoniae. In many cases, the weight loss is non-responsive to long term antibiotic therapy. In order to determine the relationships between the severity of post arrival weight loss and disease and its potential immunological or physiological indicators, tumour necrosis factor (TNF) and acute phase reactant levels were correlated with the clinical status in immunologically naive boars following their transfer to a conventional facility. Boars had higher TNF (P < 0.0001) and plasma protein (P = 0.0054) levels and decreased zinc (P = 0.0004) levels during periods of clinical sickness. Likewise, peak and average plasma TNF, serum haptoglobin, and serum zinc were correlated indicating a prolonged stress or pathogenic insult (r = 0.89, P < 0.0001 for TNF; r = 0.67, P = 0.01 for haptoglobin; r = 0.73, P = 0.005 for zinc). An acute phase response, a systemic TNF increase and the development of a lymphopenia were observed in post arrival disease in swine. This is the first time cytokines and acute phase reactants have been investigated in a field study involving immunologically naive or high health swine.
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PMID:Association of tumour necrosis factor and acute phase reactant changes with post arrival disease in swine. 932 28

The immune system changes during the lifespan of man. Many described changes in the immune system of the elderly were dependent on illness or chronic diseases. To exclude these pathological changes in the immune system and to exclusively describe age-dependent changes, Ligthart et al. defined immunogerontological criteria to study the immune system in the elderly, the SENIEUR-Protocol. Most changes in the immune system of elderly are within the normal ranges of the appropriate parameter. However, there are many significant differences between the status of the immune system in healthy young and elderly individuals, within these normal ranges. The comparison between SENIEUR-elderly and healthy young and the additional comparison of these two groups with centenarians allows the discussion of potential pathological effects of these changes. In this article we summarize the described changes of the immune system in SENIEUR-elderly and centenarians. The serum levels of the immunoglobulins G, M and A increased with age, as well as the number of benign monoclonal gammopathies and the number of autoantibodies. The titers of zinc are significantly decreased in the serum of the elderly. The production of the acute phase protein C-reactive protein is not age-dependent, whereas the serum levels of alpha 2-macroglobulin are significantly increased in the elderly. The number of lymphocytes decreased and the number of neutrophils increased with aging. Monocytes, basophils, and eosinophils are without changes during life. There are many descriptions about changes of the leukocyte sub-population in aging, which are not always comparable. However, the number of T cells (CD3) decreases. Within the T cells the CD8 cells decreased more than the CD4 cells, resulting in an increased CD4/CD8 ratio. Memory T cells (CD45RO) increase during life, whereas naive T cells (CD45RA) decrease. Interestingly, centenarians have more naive T cells SENIEUR-elderly. The number of B cells (CD19) decreased also, whereas the number of natural killer (NK) cells (CD16, CD56, CD57) increases with aging. The capacity of leukocytes from the elderly to produce cytokines is also significantly different from those of the young. The release of the TH1-cytokines interleukin (IL)-2 and interferon (IFN)-gamma is decreased, whereas the production of the TH2-cytokines IL-4 and IL-10 is increased in the elderly. The production of proinflammatory cytokines such as IL-1, IL-6, IL-8, and tumor necrosis factor-alpha is increased in the elderly. In contrast, the capacity to produce the antiviral cytokine IFN-alpha is reduced in elderly individuals. In conclusion, the immune system shows many age-dependent changes, but we know little about the reason and the potential pathological effects of these changes.
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PMID:[Characteristics of immunologic test values in the elderly]. 933 53


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