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)

Interleukin-2 receptor (IL-2R) is expressed on activated lymphocyte after stimulation with antigen or interleukin-2 (IL-2), meanwhile soluble form of the receptor is released. Using enzyme-linked immunosorbent assay, serum IL-2R levels were determined in 34 healthy controls, 61 patients with systemic lupus erythematosus (SLE) and 32 patients with rheumatoid arthritis (RA), yielding mean +/- SD values of 355 +/- 89, 807 +/- 453 and 567 +/- 210 U/ml respectively. In both SLE and RA patients, the active disease group had more markedly elevated serum IL-2R levels compared with those of the inactive group. In patients with SLE, elevated serum IL-2R is associated with lymphopenia, renal disorders, decreased C3 level and increased anti-DNA, thus make it a good parameter to monitor disease activity in SLE.
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PMID:Serum interleukin-2 receptor in systemic lupus erythematosus and rheumatoid arthritis. 326 81

Metallothioneins that bind copper and zinc have an Mr of 6500 daltons, consist of a single polypeptide chain of 61 amino acids, 25-30 percent of whose residues are cysteine, have a metal-binding capacity of between 5 and 7 g atoms/mol, and contain no disulfide bonds or aromatic amino acids. Zincthionein has been postulated to participate in the transport and storage of zinc, which is involved in more than 235 metalloenzymes, including thymidine kinase, RNA polymerase, and ribonuclease, which in turn play crucial roles in the replication and transcription of DNA during cell division. In addition, trace elements including zinc modulate immune response and function. Conversely, zinc deficiency state causes, for example, thymic atrophy and lymphopenia and modifies antibody-mediated responses to both T-cell-dependent and T-cell-independent antigens. The concentrations of copper, zinc, and metallothionein and the copper/zinc ratio are modified in a number of malignancies. For example, the levels of metallothionein in normal and in malignant human livers are 471 and 75 micrograms/g, respectively. In addition, the copper/zinc ratio is significantly increased in human pancreatic cancer from 1.40 to 2.70. Furthermore, studies involving 64Cu in tumor-bearing mice showed that the distribution of 64Cu was altered and that all tumors contained a relatively high level of 64Cu. Moreover, the activity of superoxide dismutase to remove free oxygen radicals is lower in malignant tissues. Finally, the results of clinical studies suggest that the monitoring of the serum copper/zinc ratio may be a valuable tool, not only in determining the extent of malignancies, but also in predicting the efficacy of treatments.
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PMID:The status of zinc, copper, and metallothionein in cancer patients. 328 43

The predictive value of a number of clinical and laboratory variables for the mortality of 148 patients with systemic lupus erythematosus (SLE) with a mean observation period of 8 years and a 10-year-survival of 80 per cent was calculated by means of differentiated survival rate analyses and stepwise regression analyses. The predictive power of several variables increased if the calculations were based on deaths caused by SLE rather than on the total mortality rate. The survival rate decreased after 1973 because a diagnosis of SLE was made in some patients with terminal disease who would have remained without a diagnosis before that time. The causes of death and the treatment were identical before and after 1973. The presence of a high number of diagnostic ARA criteria within the first year of observation was a predictor of decreased survival. Severe but non-fatal infections (meningitis, septicemia, pneumonia) significantly reduced the survival rate. Patients with proteinuria and azotemia, within the first 2 years of observation, had a 10-year-survival of 70 per cent. The survival of patients with CNS manifestations was not significantly reduced. The butterfly rash and the presence of lymphopenia were predictors of decreased survival, whereas the presence of DNA antibodies had no predictive value for survival.
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PMID:Systemic lupus erythematosus. Follow-up study of 148 patients. II: Predictive factors of importance for course and outcome. 358 95

This article describes the immunologic and pulmonary abnormalities and the chemical composition of pleural effusion fluid in a patient with intestinal lymphangiectasia as they are effected by therapeutic measures during a 7-year period. Lymphedema was first noticed in the patient at 3 years of age, and pleural effusions developed 7 years later. Thoracentesis demonstrated that the right pleural fluid was yellow, clear, and had the composition of lymph. The left pleural fluid was milky and had a higher triglyceride and lymphocyte content than the right pleural fluid. Complete removal of pleural fluid transiently increased total lung capacity to a maximum of 52% predicted. Strict dietary management with a low-fat and high-protein diet resulted in a transient partial reversal of circulating lymphopenia and low T cell concentration. This was accompanied by a decrease in lymphocyte and T cell concentration in the pleural fluid. Unstimulated mononuclear cells from pleural fluid synthesized increased amounts of DNA, and added mitogens or antigens further increased DNA synthesis. Dietary therapy had a minimal effect on this DNA synthesis. Despite circulating hypogammaglobulinemia, normal antibody activity was detected. The proportion of B cells in pleural fluid was greater than that in the circulation, and dietary therapy did not alter this difference. Pulmonary physiology improved during the initial 9-month period of diet therapy, but then the rate of fluid accumulation increased, causing respiratory compromise. Stability was achieved by a right-sided pleurodesis, followed 18 months later by a left pleurodesis with the addition of a shunt to provide internal lymph drainage.
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PMID:Intestinal lymphangiectasia and bilateral pleural effusions: effect of dietary therapy and surgical intervention on immunologic and pulmonary parameters. 378 56

Four patients presented with the nephrotic syndrome. The histological appearances on renal biopsy were in three characteristic and in one suggestive of lupus nephritis. These patients did not initially have other clinical features of SLE, but three had a positive ANA and one a raised DNA titre. Remission occurred in two patients, in one spontaneously and in another following corticosteroid therapy, but two developed renal failure. During follow-up all developed elevated DNA binding levels and arthralgia or lymphopenia. The ARA classification criteria for lupus were only fulfilled at this late stage.
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PMID:Lupus-like nephritis heralding the definitive manifestation of systemic lupus erythematosus. 387 72

Two out of 25 monoclonal anti-DNA autoantibodies that were produced by human-human hybridoma were found to have lymphocytotoxic activity. The antibodies reacted with normal B and T lymphocytes at cold (4 degrees C) as well as at warm (37 degrees C) temperatures. The lymphocytotoxic activity of the monoclonal anti-DNA antibodies could be inhibited by prior incubation of the antibodies with either polynucleotides, e.g. poly(I), poly(dT) or anti-idiotypic antibodies, that had been raised against a dominant anti-DNA antibody. The cross-reactivity between nuclear material and lymphocyte membrane raises the question whether these apparently diverse materials have a shared epitope. The cross-reactivity between anti-DNA antibodies and lymphocyte membrane may account in part for the lymphopenia observed in systemic lupus erythematosus patients.
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PMID:Human monoclonal anti-DNA antibodies react as lymphocytotoxic antibodies. 405 10

The effects of recombinant DNA-produced leukocyte interferon (IFLrA) were studied in 37 patients with metastatic cancer who received sequentially escalating doses of 9-86 million units (MU) of IFLrA by im injection twice weekly. The IFLrA was absorbed rapidly and reached a peak serum concentration 6-8 hours after injection. Serum concentration of IFLrA increased proportionately with the dose. The most common side effects included fever, chills, asthenia, anorexia, and weight loss, and leukopenia, granulocytopenia, and lymphopenia occurred frequently. Elevation of serum glutamic-oxaloacetic transaminase was frequent above doses of 50 MU. All side effects were reversible by discontinuation of the drug. Antibodies to IFLrA were detected in 3 patients while on treatment. The presence of antibodies coincided with drastic reduction in serum IFLrA concentration and, in 1 patient, with relapse of disease. Objective tumor responses were documented in patients with lymphomas but not in other groups of patients.
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PMID:Clinical study of recombinant DNA-produced leukocyte interferon (clone A) in a intermittent schedule in cancer patients. 619 33

Deoxyadenosine (AdR) appears to be central to the molecular events mediating immunodeficiency in children born with adenosine deaminase (ADA) deficiency but it is still uncertain whether lymphotoxicity is due to AdR directly inhibiting transmethylation reactions in which S-adenosylmethionine is the methyl group donor, or is due to phosphorylation of AdR to deoxyadenosine triphosphate (dATP) which then inhibits ribonucleotide reductase or is due to other mechanisms. Using AdR and the ADA inhibitor deoxycoformycin (dCF) and assessing cell viability, nucleoside incorporation into RNA and DNA, as well as measuring deoxyribonucleoside triphosphate (dNTP) concentrations and S-adenosylhomocysteine (SAH) hydrolase activity, we have studied various types of human lymphoid cells and demonstrated in them the relative importance of the above two mechanisms of AdR toxicity. Treatment of normal resting peripheral blood lymphocytes in culture with AdR and dCF resulted in impaired viability. Although elevated dATP levels as well as decreased SAH hydrolase activities were both observed, the failure of a known inhibitor of ribonucleotide reductase (hydroxyurea) to produce toxicity, and the inability of deoxycytidine (CdR) to achieve a rescue effect, point to another mechanism, possibly inhibition of trans-methylation or ATP depletion being the more likely causes of toxicity in resting lymphocytes. The same mechanism may well account for the rapid and severe lymphopenia in patients treated with dCF. On the other hand, in cultured lymphoblasts in the exponential phase of growth. AdR and dCF produced marked inhibition of growth and cell death both in a Thy-ALL line and in a c-ALL line, in the absence of significant inhibition of SAH hydrolase, but with a substantial elevation in dATP concentrations and depressed levels of the other dNTP. Minor toxicity occurred in a proliferating B lymphoblast line despite almost complete inactivation of SAH hydrolase. These observations indicate inhibition of ribonucleotide reductase as the more likely mechanism of toxicity in rapidly proliferating lymphocytes. Other T-cells actively synthesizing DNA, such as PHA-stimulated or MLC activated lymphocytes and T-lymphoid colony forming cells, are also likely to be affected by the same mechanism. Indeed in PHA-stimulated lymphocytes, deoxycytidine caused significant although incomplete rescue from toxicity due to dCF and AdR. In patients with ADA deficiency or treated with ADA inhibitors, both mechanisms could be operative. These observations are also relevant to the possible use of dCF and AdR as immunosuppressive agents and for the removal of T-cells or residual Thy-ALL blasts from bone marr
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PMID:Mechanisms of deoxyadenosine toxicity in human lymphoid cells in vitro: relevance to the therapeutic use of inhibitors of adenosine deaminase. 623 Oct 47

Accumulation of dATP derived from 2'-deoxyadenosine (dAdo), causing inhibition of ribonucleotide reductase and depletion of the other deoxynucleotide substrates required for DNA synthesis, has been suggested as the cause of the lymphopenia and immune defect in inheritable deficiency of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4). dAdo also inactivates the enzyme S-adenosylhomocysteine hydrolase (AdoHcyase; S-adenosyl-L-homocystein hydrolase EC 3.3.1.1) which is involved in the catabolism of S-adenosyl-L-homocysteine (AdoHcy), both a product and a potent inhibitor of S-adenosylmethionine-dependent transmethylation. We have tried to determine whether inactivation of AdoHcyase might also contribute to dAdo toxicity to adenosine deaminase-inhibited cells. dAdo rapidly inactivates intracellular AdoHcyase and causes the accumulation of AdoHcy in WI-L2 human B lymphoblastoid cells. Low concentrations of adenosine (Ado), which block binding of dAdo to purified AdoHcyase, prevented inactivation of intracellular AdoHcyase and also lessened the growth-inhibitory effect of dAdo. A mutant of this cell line which lacks Ado kinase and accumulated endogenously synthesized Ado was resistant to the effects of dAdo on both growth and AdoHcyase activity. The mutant also accumulated far less dATP from dAdo than did its parent and was resistant to the inhibitory effect of dAdo on DNA synthesis, indicating the Ado kinase is involved in dAdo phosphorylation in these cells. Combinations of deoxycytidine, thymidine, and deoxyguanosine that could prevent dATP-mediated depletion of deoxynucleotide pools but not AdoHcyase inactivation were less effective than Ado in preventing dAdo toxicity to normal lymphoblasts. Our results suggest that inactivation of AdoHcyase, as well as dATP accumulation, contributes to dAdo toxicity.
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PMID:Resistance of an adenosine kinase-deficient human lymphoblastoid cell line to effects of deoxyadenosine on growth, S-adenosylhomocysteine hydrolase inactivation, and dATP accumulation. 625 19

An inherited deficiency of adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) produces selective lymphopenia and immunodeficiency disease in humans. Previous experiments have suggested that lymphospecific toxicity in this condition might result from the selective accumulation of toxic deoxyadenosine nucleotides by lymphocytes with high deoxycytidine kinase, levels and low deoxynucleotide dephosphorylating activity. The present experiments were designed to determine if deoxyadenosine analogs which are not substrates for adenosine deaminase might similarly be toxic toward lymphocytes and lymphoid tumors. Two such compounds, 2-chlorodeoxyadenosine and 2-fluorodeoxyadenosine, at concentrations of 3 nM and 0.15 microM, respectively, inhibited by 50% the growth of human CCRF-CEM malignant lymphoblasts in vitro. Each was phosphorylated in intact cells by deoxycytidine kinase accumulated as the nucleoside triphosphate, and inhibited DNA synthesis more than RNA synthesis. Both deoxynucleosides had significant chemotherapeutic activity against lymphoid leukemia L1210 in mice.
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PMID:Deoxycytidine kinase-mediated toxicity of deoxyadenosine analogs toward malignant human lymphoblasts in vitro and toward murine L1210 leukemia in vivo. 625 65


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