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)

Athletes are exposed to acute and chronic stress that may lead to suppression of the immune system and increased oxidative species generation. In addition, the tendency to consume fewer calories than expended and to avoid fats may further compromise the immune system and antioxidant mechanisms. The exercise stress is proportional to the intensity and duration of the exercise, relative to the maximal capacity of the athlete. Muscle glycogen depletion compromises exercise performance and it also increases the stress. Glycogen stores can be protected by increased fat oxidation (glycogen sparing). The diets of athletes should be balanced so that total caloric intake equals expenditure, and so that the carbohydrates and fats utilised in exercise are replenished. Many athletes do not meet these criteria and have compromised glycogen or fat stores, have deficits in essential fats, and do not take in sufficient micronutrients to support exercise performance, immune competence and antioxidant defence. Either overtraining or under nutrition may lead to an increased risk of infections. Exercise stress leads to a proportional increase in stress hormone levels and concomitant changes in several aspects of immunity, including the following: high cortisol; neutrophilia; lymphopenia; decreases in granulocyte oxidative burst, nasal mucociliary clearance, natural killer cell activity, lymphocyte proliferation, the delayed-type sensitivity response, the production of cytokines in response to mitogens, and nasal and salivary immunoglobulin A levels; blunted major histocompatibility complex II expression in macrophages; and increases in blood granulocyte and monocyte phagocytosis, and pro- and anti-inflammatory cytokines. In addition to providing fuel for exercise, glycolysis, glutaminlysis, fat oxidation and protein degradation participate in metabolism and synthesis of the immune components. Compromising, or overusing, any of these components may lead to immunosuppression. In some cases, supplementation with micronutrients may facilitate the immune system and compensate for deficits in essential nutrients. In summary, athletes should eat adequate calories and nutrients to balance expenditure of all nutrients. Dietary insufficiencies should be compensated for by supplementation with nutrients, with care not to over compensate. By following these rules, and regulating training to avoid overtraining, the immune system can be maintained to minimise the risk of upper respiratory tract infections.
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PMID:Effect of dietary intake on immune function in athletes. 1192 59

The purpose of this study is to determine the toxicity and efficacy of temozolomide (TMZ) p.o. followed by subcutaneous (s.c.) low-dose interleukin-2 (IL2), granulocyte-monocyte colony stimulating factor (GM-CSF) and interferon-alpha 2b (IFN alpha) in patients with metastatic melanoma. A total of 74 evaluable patients received, in four separate cohorts, escalating doses of TMZ (150-250 mg m(-2)) for 5 days followed by s.c. IL2 (4 MIU m(-2)), GM-CSF (2.5 microg kg(-1)) and IFN alpha (5 MIU flat) for 12 days. A second identical treatment was scheduled on day 22 and cycles were repeated in stable or responding patients following evaluation. Data were analysed after a median follow-up of 20 months (12-30 months). The overall objective response rate was 31% (23 out of 74; confidence limits 20.8-42.9%) with 5% CR. Responses occurred in all disease sites including the central nervous system (CNS). Of the 36 patients with responding or stable disease, none developed CNS metastasis as the first or concurrent site of progressive disease. Median survival was 252 days (8.3 months), 1 year survival 41%. Thrombocytopenia was the primary toxicity of TMZ and was dose- and patient-dependent. Lymphocytopenia (grade 3-4 CTC) occurred in 48.5% (34 out of 70) fully monitored patients following TMZ and was present after immunotherapy in two patients. The main toxicity of combined immunotherapy was the flu-like syndrome (grade 3) and transient liver function disturbances (grade 2 in 20, grade 3 in 15 patients). TMZ p.o. followed by s.c. combined immunotherapy demonstrates efficacy in patients with stage IV melanoma and is associated with toxicity that is manageable on an outpatient basis.
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PMID:Temozolomide followed by combined immunotherapy with GM-CSF, low-dose IL2 and IFN alpha in patients with metastatic melanoma. 1261 Apr 99

Twenty pigs were inoculated with a virulent isolate (Quillota strain) of classical swine fever (CSF) virus to determine the chronological development of lesions in bone marrow. Histopathologic, ultrastructural and immunohistochemical (detection of viral antigen gp55, myeloid-histiocyte antigen, CD3 antigen, and FVIII-rag), and morphometric techniques were employed. Viral antigen was detected from 2 days postinfection (dpi) in stromal and haematopoitic cells, and severe atrophy related to apoptosis of haematopoitic cells was observed. Megakaryocytes (MKs) did not show significant changes in number, but there were important qualitative changes including 1) increased numbers of cloud-nuclei MKs, microMKs, apoptotic MKs, and atypical nucleated MKs and 2) decreased number of typical nucleated MKs. Morphometric study of these cells showed a decrease in cytoplasmic area. MK infection was detected from 2 dpi, but in a small percentage of cells. Myeloid cells showed quantitative changes, with an increase in granulocyte numbers. Apoptosis of lymphocytes and viral infection of erythroblasts were also observed. The main changes in stroma were depletion of T lymphocytes in the middle phase of the experiment and macrophages. Viral infection was also observed in these cells. MK lesions suggest dysmegakaryocytopoiesis, which would aggravate the thrombocytopenia already present and could be responsible for it. Granulocyte changes would lead to the appearance of circulating immature forms, whereas lymphocyte apoptosis in bone marrow would contribute to lymphopenia.
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PMID:Classical Swine Fever: pathology of bone marrow. 1263 55

Magnesium status is a well-known modulator of the immune system. In the present study we investigated the effect of magnesium on granulocyte signalling and function. Furthermore, we performed a double-blinded randomised study investigating the effect of a two-month magnesium supplementation period on the exercise-associated alterations in immune function. In vitro incubation of granulocytes in media of different magnesium composition resulted in significant changes in chemotactic peptide-induced calcium transients while basal calcium levels were not affected. Likewise, the stimulus-induced formation of free radicals was affected by extracellular magnesium while phagocytosis of granulocytes was not affected. In the second part of the study we investigated whether a two-month period of magnesium supplementation was able to diminish alterations in immune cell counts and functions after an exercise test until exhaustion. The magnesium status was similar in both human and placebo groups and did not change significantly after the supplementation period. Exhaustive exercise induced an activation of the immune system as indicated by an increase in granulocyte count and a post-exercise lymphopenia. In addition, chemotactic peptide-induced cellular calcium transients were enhanced post-exercise while oxidative burst and phagocytosis were decreased. These results suggest that magnesium is an important modulator of immune cell function under in vitro conditions. However, a magnesium supplementation seems to be unable to prevent any exercise-associated alterations in immune cell function in athletes with balanced magnesium status.
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PMID:Effect of magnesium on granulocyte function and on the exercise induced inflammatory response. 1273 83

Fusarium species frequently implicated in human infections include F. solani, F. oxysporum and F. moniliforme. Among immunocompetent patients, tissue breakdown (as caused by trauma, severe burns or foreign body) is the risk factor for fusariosis. Infections include keratitis, onychomycosis and occasionally peritonitis and cellulitis. Treatment is usually successful and requires removal of the foreign body as well as antifungal therapy. Among immunocompromised patients, mainly patients with haematological malignancies, Fusarium spp. are the second most common pathogenic mould. Risk factors for disseminated fusariosis include severe immunosuppression (neutropenia, lymphopenia, graft-versus-host disease, corticosteroids), colonisation, tissue damage, and receipt of a graft from an HLA-mismatched or unrelated donor. Clinical presentation includes refractory fever (> 90%), skin lesions and sino-pulmonary infections ( approximately 75%). Type of skin lesions includes ecthyma-like, target, and multiple subcutaneous nodules. Skin lesions lead to diagnosis in > 50% of patients and precede fungemia by approximately 5 days. In contrast to disseminated aspergillosis, disseminated fusariosis can be diagnosed by blood cultures in 40% of patients. Histopathology reveals hyaline acute-branching septate hyphae similar to those found in aspergillosis. Mortality from fusarial infections in immunocompromised patients ranges from 50% to 80%. Host immune status is the single most important factor predicting outcome. Persistent neutropenia and corticosteroid therapy significantly affect survival. Optimal treatment has not been established. Anecdotal successes have been reported with various agents (high-dose amphotericin B, lipid-based amphotericin B formulations, itraconazole, voriconazole) and with cytokine-stimulated granulocyte transfusions. Preventing fusariosis relies on detection and treatment of cutaneous damage prior to commencing immunosuppression and decreasing environmental exposure to Fusaria (via air and water).
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PMID:Human fusariosis. 1474 3

Differential expression of Hox genes is associated with normal hematopoiesis, whereas inappropriate maintenance of Hox gene expression, particularly Hoxa7 and Hoxa9, is a feature of leukemias harboring mixed-lineage leukemia (MLL) mutations. To understand the pathogenic roles of Hox genes in MLL leukemias, we assessed the impact of Hoxa7 or Hoxa9 nullizygosity on hematopoietic progenitor compartments and their susceptibility to MLL-induced leukemias. Selective reductions in the absolute numbers of committed progenitors, but not of hematopoietic stem cells, distinguished Hoxa7- and Hoxa9-deficient mice. Megakaryocytic/erythroid progenitor (MEP) reductions in Hoxa7(-/-) mice correlated with reticulocytosis and thrombocytopenia without anemia. Conversely, Hoxa9(-/-) mice displayed marked lymphopenia and substantial reductions of common lymphoid progenitors (CLPs) and lymphoid precursors, in addition to significant reductions of common myeloid progenitors (CMPs) and granulocyte/monocyte progenitors (GMPs). In retroviral transduction/transplantation assays, Hoxa7- and Hoxa9-deficient progenitors remained susceptible to transformation by MLL-GAS7, which activates MLL through a dimerization-dependent mechanism. However, Hoxa7(-/-) or Hoxa9(-/-) progenitors were less efficient in generating transformed blast colony-forming units (CFUs) in vitro and induced leukemias with longer disease latencies, reduced penetrance, and less mature phenotypes. Thus, Hoxa7 and Hoxa9 contribute to hematopoietic progenitor homeostasis but are not necessary for MLL-GAS7-mediated leukemogenesis, yet they appear to affect disease latency, penetrance, and phenotypes consistent with their critical roles as downstream targets of MLL fusion proteins.
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PMID:Leukemic transformation of hematopoietic progenitors by MLL-GAS7 in the absence of Hoxa7 or Hoxa9. 1507 Jul 2

It has been suggested that monocytes/macrophages represent the pivotal cell type during early adaptive growth of pre-existent arterial anastomoses toward functional collateral arteries (arteriogenesis) upon arterial occlusion. This hypothesis was supported by previous studies providing evidence that elevation of the peripheral monocyte count, increased monocyte survival (e.g., granulocyte macrophage-colony stimulating factor), as well as enhanced attraction or adhesion (e.g., monocyte chemoattractant protein 1; intercellular adhesion molecule 1) of the latter cells correlates directly with the arteriogenic response to restore tissue perfusion. However, the experimental proof of the essential role of monocytes/macrophages remains to be given. We therefore hypothesized that arteriogenesis is reduced in a genuine, nonpharmocologically induced monocyte/macrophage-deficient model of femoral artery occlusion in osteopetrotic (op/op) mice. Total leukocyte count did not differ between op/op mice and control (B6C3Fe a/a-Csf1(+/+)) mice. op/op mice show a significant monocytopenia (0.67%+/-0.38% vs. 1.53%+/-0.32%), granulocytosis (33.66%+/-6.67% vs. 22.83+/-7.47%), and a concomitant, relative lymphopenia (65.67%+/-6.58% vs. 75.65%+/-7.31%). Microsphere-based perfusion measurement 7 days after femoral artery occlusion demonstrated a significantly reduced perfusion restoration upon femoral artery occlusion in op/op mice as compared with controls (28.19%+/-0.91% vs. 47.88%+/-2.49%). The application of a novel method of high resolution (microfocus X-ray system) angiography revealed a reduction of proliferation and diameter of collateral arteries. Quantitative immunohistology showed significantly lower numbers of macrophages in the surrounding tissue of proliferating arteries. This study provides additional evidence for the preeminent role of monocytes/macrophages during arteriogenesis in a genuine model of monocyte deficiency, i.e., without pharmacological intervention.
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PMID:Arteriogenesis depends on circulating monocytes and macrophage accumulation and is severely depressed in op/op mice. 1668 92

In an effort to further elucidate the complex changes in the complement-leukocyte system during cardiopulmonary bypass (CPB), plasma levels of C3d, C5a, and granulocyte elastase bound to alpha1-proteinase inhibitor (E-alpha1 PI) were followed prior to, during, and after CPB. Leukocyte and differential cell counts and granulocyte migration were also determined. Complement activation was documented during CPB by an increase in plasma C3d corrected for hemodilution. Significant amounts of C5a were not revealed. Cell counts decreased during CPB but, if corrected for hemodilution, remained unchanged apart from a slight decrease in lymphocyte count after 60 minutes. Eighteen hours after CPB, neutrocytosis and lymphopenia occurred. Plasma E-alpha1 PI increased during CPB, reflecting release of granulocyte lysosomal enzymes. Granulocyte migration was transitorily depressed during CPB, and it was shown that this was due to the appearance of an intrinsic cellular defect. CPB is associated with acute changes in cells and plasma, resembling an acute whole-body inflammatory response, with transitory impairment of granulocyte migration. The clinical significance of these observations remains to be determined.
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PMID:Complement and leukocytes during cardiopulmonary bypass: effects on plasma C3d and C5a, leukocyte count, release of granulocyte elastase and granulocyte chemotaxis. 1717 7

C3H mice (H-2 locus = k, hemoglobin D) received marrow cells intravenously following supralethal total-body x-irradiation. Donors were C3H, AKR (k, hemoglobin D), C57BR (k, hemoglobin S), A (a, hemoglobin D), and C57BL (b, hemoglobin S). Compatible marrow recipients suffered 20 % mortality. Incompatible H-2 and hemoglobin donation resulted in 97 % (mortality by the twenty-fifth day. H-2-compatible, hemoglobin-incompatible recipients suffered 67 % mortality by the fortieth day and then no further mortality. The H-2-incompatible, hemoglobin-compatible donation resulted in 36 % mortality by the fortieth day and showed continued mortality thereafter. Peripheral blood hematocrit and granulocyte counts and bone marrow cellularity and DNase activity revealed no significant differences, demonstrating successful grafts in all groups. However, the recovery of peripheral blood lymphocytes was inversely related to the mortality. Lymphopoiesis is apparently inhibited when the transplanted lymphocytes encounter overwhelming concentration of foreign antigens in the host. The H-2-compatible, hemoglobin-incompatible graft replaces the host's erythrocytes, thereby eliminating the inhibition of the graft's lymphocytic proliferation by that host antigen. During the first 40 days, homologous deaths result primarily from the effects of lymphopenia; thereafter, with recovery of lymphopoiesis, deaths are probably due to graft versus host reaction.
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PMID:Hematological response to isologous and homologous bone marrow transplantation: mechanism of homologous failure. 1738 24

Paclitaxel (single intravenous injection in a maximum tolerated dose of 4.6 mg/kg) to white outbred rats causes bone marrow hypoplasia, increased granulocyte and erythroid cell mitosis (metaphase-anaphase transition), and moderate pancytopenia developments in peripheral blood (hypoplastic anemia, deep, short-term neutropenia, lymphopenia and thrombocytopenia) in the first hours after injection. A considerable increase of polyploidy (4n) cells and a moderate increase in the structural changes (chromatid deletions) of chromosomes was observed on bone marrow metaphase plates in 24 h. The drug introduction causes earlier increase in the rate of thymus cells mitosis, a growth in the number of thymocytes with apoptosis signs, and a moderate decrease in the thymus and spleen weight. All changes are reversible. Long-term (90 days after injection) observation revealed decreased lymphocyte count in the peripheral blood and bone marrow and earlier thymus involution.
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PMID:[Myelotoxicity of paclitaxel (mitotax)]. 1807 42


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