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)

Mice bearing the immunosuppressive plasmacytoma TEPC-183 exhibit a marked splenic hyperplasia. We have characterized these tumor-reactive splenocytes on the basis of cell surface marker expression, nonspecific esterase activity, and morphology. Although splenocyte numbers increased progressively throughout tumor growth, B- and T-lymphocytes, as defined by surface immunoglobulin and Thy-1 antigen expression, respectively, did not increase significantly. Fourteen days after tumor implantation, T-lymphocytes decreased from 70 million to 50 million per spleen. However, cells expressing Mac-1 antigen or nonspecific esterase activity increased from 10 to 65 million. This constituted a 6-fold increase in splenic macrophages. Further studies utilizing the expression of PC.2 antigen in conjunction with morphological examination indicated that metastatic TEPC-183 cells comprise approximately 5% of the tumor-host splenocyte population 14 days after implantation. Ablation of plasmacytoma by cyclophosphamide inhibited the tumor-associated splenocytosis and led to an increase in splenic T-cells (from 70 to 120 million). In addition, macrophage numbers returned to normal. This study also assessed the ability of splenocytes from animals with either actively growing tumors or those from cyclophosphamide-treated tumor-bearing mice to mediate an antitumor response. Splenocytes, when assessed 1 wk following tumor ablation by cyclophosphamide, demonstrated antitumor activity in Winn neutralization assays. This activity was not detectable in splenocytes from animals with progressively growing tumors. Additional studies revealed that the cell population involved in the antitumor effect was glass nonadherent, nylon-wool nonadherent, and expressed Thy-1 antigen. These observations were consistent with the expansion of the splenic T-lymphocyte population following cyclophosphamide treatment. However, the immune response directed against primary TEPC-183 tumor cells was not inhibitory to metastatic tumor cells.
Cancer Res 1985 Dec
PMID:Cellular changes and antitumor responses in the plasmacytoma-bearing mouse following cyclophosphamide treatment. 286 30

T-lymphotropic retroviruses of cats cause lymphopenia and immunosuppression and represent the major cause of death in that species. Similarly HTLV-I which is T4 tropic is associated with an increased risk for development of infectious disease in regions where the virus is endemic. Since HTLV-I is also believed to be transmitted by blood and by sexual intercourse we considered the possibility that a variant form of HTLV might cause AIDS. The identification of cross-reactive antibodies to HTLV-I-MA in a third or more of the AIDS patients and in suspicious blood donors that donated to transfusion-associated cases of AIDS eventually led to the recognition of HTLV-III, the causative agent of AIDS. The protein most associated with lymphocyte immortalization or transformation in the case of HTLV-I is p42. The proteins of HTLV-I encoded by the amino terminus of the env gene designated gp61 and gp45 are the most immunogenic antigens of this virus. Similarly those encoded by the amino terminus of the env gene HTLV-III designated gp160 and gp120 appear to be the most immunogenic markers for this agent. Almost all AIDS patients, ARC patients, and asymptomatic hemophiliacs have detectable antibodies to gp120 and gp160. HTLV-III related agents designated STLV-III have been found in macaque monkeys that develop simian AIDS and high prevalence rates of antibodies to STLV-III can be found in healthy African green monkeys. We hypothesize that the STLV-III of African green monkeys could represent a recent source of the virus to have infected humans in central Africa where the human epidemic probably began. The recognition that up to one million people may already be infected with HTLV-III in the United States alone indicates the need for development of a vaccine. The availability of primate species infected with the serologically related STLV-III agents that either resist disease development (African green monkeys) or succumb to an AIDS-type syndrome (rhesus) provide models that should aid in our attempts to develop such vaccines.
Cancer Res 1985 Sep
PMID:Retroviruses associated with leukemia and ablative syndromes in animals and in human beings. 299 Jun 82

The kinetics of lymphocyte migration in 12 pre-treatment patients with nasopharyngeal carcinoma (NPC) and three cancer controls in remission were studied with Indium III oxine-labelled autologous lymphocytes. The migratory patterns of the labelled lymphocytes were defined by serial gamma imaging and blood clearance of Indium over 72 h. Once in the systemic circulation the labelled lymphocytes migrated immediately to the liver and spleen. In all the subjects studied the lymphocytes began to migrate out of the liver at 0.5 h, only to return to the organ gradually between 2 and 72 h. In the control subjects the lymphocytes migrated out of the spleen from about 4 h. This coincided with a hump in the peripheral blood clearance curve after about 4 h signifying re-entry of the lymphocytes into the vascular space from the spleen. In the 'early' NPC subjects (Stage I-III) the rate at which the lymphocytes entered the spleen was much reduced from about 4 to 72 h, suggesting a prolonged transit time of the lymphocyte through the organ. However, there were still prominent humps in the blood clearance curves, suggesting significant re-entry of lymphocytes into the vascular space. In the 'late' NPC subjects (Stage IV-V), the activity of the spleen was low between 4 and 72 h and there was continuous sequestration of lymphocytes in the organ. Consequently the humps in the blood clearance curves were much reduced or absent. The activities of the metastatic lymph nodes were intense between 2 and 48 h, suggesting marked sequestration of lymphocytes in the diseased lymph nodes. Migration of lymphocytes in the metastatic area of the liver was notably absent and presented as cold areas on gamma scanning. The sequestration of lymphocytes in the spleen and metastatic lymph nodes in 'early' and 'late' NPC could lead to a contraction of intravascular lymphocyte pool and could explain the stage-dependent lymphopenia reported in NPC.
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PMID:A study of lymphocyte kinetics in nasopharyngeal carcinoma with indium III oxine-labelled lymphocytes. 314 79

Tumoricidal activity of Soviet-synthesized oxoplatinum and cycloplatam was shown to influence human tumor strains (melanoma, cancer of the kidney, Burkitt's lymphoma) transplanted to nude mice. Their therapeutic effect was associated with lymphopenia; however, they did not suppress the chemically determined activity of succinate dehydrogenase and alpha-glycerophosphate dehydrogenase.
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PMID:[Comparative study of platinum complexes in athymic mice with human tumors]. 318 35

Oxoplatinum (USSR) caused a more pronounced anticancer effect than platidiam (CSSR) when treating nude mice with the transplantable human melanoma. Moderate lymphopenia was found with therapeutic doses of oxoplatinum and platidiam, but there was no direct inhibition of the energy metabolism of lymphocytes in the peripheral blood. In the cancer cells and in the lymphocytes infiltrating the tumour oxoplatinum caused a significant decrease in the alpha-GPDG activity realizing the binding of the glycolysis and oxidation which might evidence for a definite selective action of oxoplatinum on the human melanoma.
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PMID:[Effect of oxoplatin and platidiam on human melanoma strains and functional activity of blood lymphocytes in athymic mice]. 320 91

The quantitation of cells bearing CD3, CD4, CD8, and B cell phenotypic markers, as well as an estimation of serum immunoglobulin (Ig)G, IgA, and IgM, was carried out in a group of 39 glioma patients with different grades of malignancy. The findings were compared with those obtained from 21 normal healthy control subjects. The analysis revealed a significant decrease both in the absolute numbers and in the percentages of circulating CD3+ (p less than 0.001) and CD4+ (p less than 0.001) cells, while the CD8+ and Pan B+ cells remained within the normal range irrespective of the type and grade of tumor. The CD4+:CD8+ ratio was significantly decreased in all categories of patients. The CD4 lymphopenia was also evident in 10 patients who had no history of previous immunosuppressive drug therapy (steroids and anticonvulsants) until the commencement of the study. The Ig levels were within the normal range in patients with malignant astrocytoma and glioblastoma multiforme, whereas a three- and fourfold increase in the IgM level was observed in patients with astrocytoma. It is suggested that T cell lymphopenia in glioma patients could mainly be due to a selective depletion of CD4+ cells and that it occurs principally as a reaction to the tumor.
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PMID:Imbalances in T cell subpopulations in human gliomas. 325 64

Adoptive immunotherapy with interleukin 2 (IL-2) and lymphokine-activated killer (LAK) cells (IL-2/LAK) is a technically demanding cancer therapy dependent upon large scale isolation and culture of lymphocytes. An important question is whether this technology can be accomplished routinely outside of highly specialized centers. In addition, no systematic examination of laboratory correlates of IL-2/LAK therapy in humans has been reported to date. The objectives of this report are to address two issues relevant to IL-2/LAK therapy. (a) Can IL-2/LAK therapy be accomplished outside of previously identified centers of expertise? (b) What are the relevant laboratory/clinical parameter correlations? The six institutions in the National Cancer Institute extramural trial treated 83 evaluable patients with renal cancer, malignant melanoma, or colon cancer with IL-2/LAK by a uniform protocol. Patients received 5 days of IL-2 priming, then daily leukaphereses for 5 days starting 48 h after IL-2 to harvest cells. Mononuclear cells were isolated, then cultured in roller bottles in 1-liter aliquots for 3 to 4 days at a cell density of 1.5 x 10(6) per ml with recombinant IL-2, 1500 units per ml. Cells were harvested and administered to patients with additional IL-2. Administration of IL-2 regularly induced lymphopenia and rebound lymphocytosis. Leukapheresis yields and numbers of LAK cells generated in culture and reinfused into patients correlated directly with peak lymphocyte counts achieved by IL-2 administration. Mean mononuclear cell recovery per 5 days of leukapheresis (+/- SEM) was 14.3 +/- 0.8 x 10(10). Average volume of cells cultured per patient was 95 liters (range, 41 to 235). Mean yield of cells harvested from cultures was 53%. Mean total number of LAK cells infused per patient was 7.6 +/- 0.4 x 10(10) (range, 2 to 15.2 x 10(10]. LAK activity was measured in vitro by lysis of 51Cr-labeled natural killer-resistant Daudi and fresh tumor targets. LAK effector cells regularly lysed these targets in vitro. Neither tumor reduction nor clinical toxicity correlated with dose or with cytolytic activity of LAK cells, or with other laboratory parameters including base-line lymphocyte count and IL-2-induced lymphocytosis. We conclude: (a) large quantities of LAK effector cells with tumoricidal activity can be generated routinely at different centers; (b) neither in vitro LAK activity nor numbers of LAK cells infused were predictive of clinical efficacy or toxicity. There is a need to identify other laboratory or clinical parameters more predictive of IL-2/LAK therapeutic efficacy or toxicity.
Cancer Res 1988 Aug 01
PMID:Laboratory correlates of adoptive immunotherapy with recombinant interleukin-2 and lymphokine-activated killer cells in humans. 326 May 37

Sixteen patients with metastatic melanoma or metastatic renal cell carcinoma were treated with six weekly 24-hour infusions of recombinant interleukin-2. At least three patients were treated at each dose, beginning at 3.0 mU/m2 for 24 hours each week for 6 weeks. Subsequent patients were treated at 4.5, 6.0, 8.0, and 10.0 mU/m2 for 24 hours. The incidence of diarrhea, rigors, rash, edema, and symptomatic hypotension was positively correlated with dose level. Symptomatic hypotension was dose limiting at the 10-mU/m2 level. Fever, nausea, and vomiting were seen at each dose level and could not be correlated with dose level. Lymphopenia and eosinophilia were observed at the completion of each 24-hour infusion, and an increase in peripheral blood absolute lymphocytes and eosinophils was observed over the 6-week treatment period. No thrombocytopenia was observed. No change in delayed-type hypersensitivity (type IV) as determined by skin testing could be demonstrated at any dose level. Natural killer cell cytotoxicity of peripheral blood lymphocytes increased over the treatment period, but the increase was unrelated to dose level in the range studied. One minor response was documented in a patient with renal cell carcinoma.
J Natl Cancer Inst 1988 Oct 19
PMID:Phase I study of weekly 24-hour infusions of recombinant human interleukin-2. 326 71

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

HIV infection in pediatric patients is a multisystem chronic disease that manifests as a clinical spectrum from asymptomatic infection through symptomatic infection with opportunistic infections and malignancies. The hematopoietic system is involved early in the systemic manifestations of this disease. The hematologic abnormalities seen are most probably a reflection of persistent viral infection, inflammation, and immune dysregulation, and may be complicated by secondary infections, chronic disease, drug toxicities, and nutritional deficiencies. Anemia and lymphopenia are commonly found in adult AIDS patients. Although both are also seen in pediatric patients, lymphopenia is much less common. Atypical lymphocytes with plasmacytoid characteristics have been identified in both adults and children. Pediatric bone marrow evaluation has shown an increase in plasma cells and plasmacytoid lymphocytes. Besides these findings, adult marrow findings include an increase in reticulum and lymphocytes appearing in a diffuse or aggregate pattern.
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PMID:Human immunodeficiency virus (HIV) infection in children. 332 80


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