Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0392674 (exhaustion)
 13,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The national preparation amixine induces interferon (IF) production in most of the people who have background values of serum IF. When the initial values of serum IF are high, after administration of amixine they decline to the background ones. A certain group of subjects (approximately 25%) is not sensitive to amixine. The IF content in the blood serum of such subjects does not change before or after administration of amixine. Its use should be limited to 4-5 administrations weekly, because its longer use leads to the exhaustion of the IF system in people.
 ...
PMID:[Interferon-inducing activity of amixin and its effect on the interferon status]. 169 10

The clinical and immune modulatory effects of interleukin-2 (IL-2) and interferon (INF) alfa-2a were examined in a phase II study in patients with metastatic renal cell carcinoma (six patients) and melanoma (eight patients). Treatment consisted in IL-2 3 MU/m2 continuous infusion days 1-4 and INF alfa-2a 6 MU/m2 subcutaneously day 1 and 4, both given on alternate weeks. Tumour response was assessed after four cycles of treatment or earlier, if necessary. Patients with stable disease or response were to be continued for another nine cycles or up to disease progression. The 14 patients received a total of 60 cycles of treatment. Major toxicities (WHO Grade III/IV) were fever, capillary leak syndrome with hypotension, nausea and vomiting, erythema with pruritus, leuco- and thrombopenia and sepsis with staphylococcus aureus. Five of 14 patients (36%) developed a self limiting autoimmune thyroiditis with HLA-DR expression on thyrocytes. Long term treatment toxicity was moderate with an average weight loss of 5% and an average fall in Karnofsky index of 10% compared to baseline. No responses were seen in renal cell carcinoma, two patients with melanoma had a partial and two a minor response with a duration of 1-7 months. Serial measurements of immune modulatory parameters showed a functional response to treatment with an increase of NK- and LAK-activity during the first two cycles, followed by a plateau and decrease during the third and fourth cycles. These findings were paralleled by a successive decline in treatment induced INF gamma response. These findings suggest, that alternative weekly treatment with IL-2 and INF alfa-2a results in an exhaustion of lytic capacity of NK- and LAK-cells and an attenuation of secondary cytokine release.
 ...
PMID:Clinical and immune modulatory effects of alternative weekly interleukin-2 and interferon alfa-2a in patients with advanced renal cell carcinoma and melanoma. 199 8

Preparation of highly active rabbit antisera (AS) to human recombinant alpha 2-interferon and their use for studying biological properties of natural and plasmid alpha-interferons are described. By exhaustion of AS by alpha 3-interferon there were prepared practically monospecific AS not reacting with antigenic determinants of alpha 3-interferon. It was found that alpha 3-interferon represented a significant portion of human lymphoblastoid interferons and was included in PH-labile alpha-interferon from serum of patients with Kaposi carcinoma. AS to alpha 2-interferon completely neutralized antiviral and antiproliferative activity of the homologous subtype alpha-interferon and stimulation of cytotoxicity of human natural killer cells induced by it. It neutralized also the same effects of the heterologous subtypes (alpha 3 and alpha F/D) and leukocytic interferon, but the neutralization level was lower. The results of the study confirmed the polyfunctional nature of the interferon molecule.
 ...
PMID:[Biological activity of human alpha-interferons studied using specific antisera]. 246 45

A low-dose interferon (IFN)-alpha regimen for the treatment of hairy cell leukemia (HCL) was evaluated by following changes in leukocyte differentiation antigens (LDA), natural killer cell (NK) and 2',5'-oligoadenylate (2-5A) synthetase activities. Due to hairy cells' (HC) weak expression of several antigens positive for T cells, B cells, NK cells and monocytes, the use of a double marker specific for hairy cells was needed to distinguish the different subpopulations. Analysis of LDA in peripheral blood (PB) showed a total normalization of the T cell and monocyte numbers within 90 days, the number of NK cells normalized in 90 to 180 d, whereas normalization of B cell number was seen only after 180 to 360 d of treatment. Mean pretreatment 2-5A synthetase activity was normal or low, but upon treatment the levels rose immediately to higher than normal values and remained high throughout the study. Pretreatment NK activity was low, but normalized after between 90 to 360 d, except in 2 patients with severe splenomegaly. In vitro incubation of peripheral blood mononuclear cells (PBMNC) with IFN-alpha induced activation of the NK and 2-5A synthetase activity in untreated patients, but with treatment these effects were gradually abolished, indicating an increasing effect of IFN-alpha in vivo with time. These results shows that the different PBMNC subpopulations and important immunological functions normalize with treatment. This normalization is, however, not seen until at least after 1 year of treatment, indicating that the treatment schedule should be longer. As no exhaustion to the effect of IFN was seen, as measured by the 2-5A synthetase activity, a continuing beneficial effect of treatment is anticipated. The increasing effect of IFN-alpha after the first signs of clinical effect suggests that the doses used in the present study were higher than necessary.
 ...
PMID:Immunological recovery and dose evaluation in IFN-alpha treatment of hairy cell leukemia: analysis of leukocyte differentiation antigens, NK and 2',5'-oligoadenylate synthetase activity. 291 94

Neonatal infection with the GBS occurs in a small fraction of exposed infants who lack specific antibody. Diminished influx of PMNs to sites of infection as a result of abnormalities in chemotaxis, bone marrow exhaustion, and to a lesser degree relative complement deficiency and decreased microbicidal activity of PMNs may be additional predisposing factors. Infection with HSV occurs more often in infants born to mothers with primary rather than secondary infection; the lack of passively acquired antibody in such infants is a possible but unproved susceptibility factor. The failure of neonates to control HSV may also be related to decreased production of or response to interferon or to decreased activity of nonimmune and immune cellular cytotoxic mechanisms. Similarly, infection with Toxoplasma and intracellular bacterial pathogens, such as Listeria, may be more severe because of the decreased generation of lymphokines and interleukins, which attract macrophages to the site of infection and enable them to kill these organisms. Much of this analysis based on in vitro and animal studies summarizes current information in a rapidly changing field rather than stating established fact. The precise age at which most of the immune functions discussed reach maturity is unknown. However, the risk of severe infection with these pathogens appears to wane by 2 to 3 months of age. Although this may partly reflect decreased exposure, we might hypothesize that immune functions that are mature by this age are those most critical for protection. Future studies focusing on changes in immune function during the first months of life may provide useful insights into the immunobiology of these diseases and direct attention to the most fruitful areas for immunologic intervention.
 ...
PMID:Immunologic basis for increased susceptibility of the neonate to infection. 351 Dec 2

Alpha/beta interferon (IFN) and gamma IFN exert widely overlapping biological effects. Still, mice with individually inactivated alpha/beta or gamma receptors exhibit variably severely reduced resistance to infection and altered immune responses. To investigate to what extent the two IFN systems are functionally redundant, we generated mice with a combined receptor defect (AG129 mice). Like mice with individual mutations, AG129 mice had no apparent anomalies, confirming that in the mouse the IFN system is not essential for normal development. These mice showed an additive phenotype with respect to antiviral defense and exhibited an increased susceptibility to lymphocytic choriomeningitis virus (LCMV) and notably vaccinia virus infection. Because of unlimited replication and subsequent rapid exhaustion of cytotoxic T lymphocyte (CTL) precursors, these mice were unable to mount a CTL response to LCMV. CD8(+)-mediated immunopathology was absent in LCMV-infected mice, and virus persisted. Vaccinia virus replicated much faster in AG129 mice, and a 10(4)-fold lower dose of vaccinia virus was sufficient to prime these mice. With the normal priming dose of 10(6) PFU, cytopathic effects and overwhelming infection possibly causing partial exhaustion of CTL interfered with the anti-vaccinia virus response. Even though global antiviral immunoglobulin G (IgG) titers were within normal ranges, the IgG subclass distribution was heavily biased toward IgG1.
 ...
PMID:Antiviral defense in mice lacking both alpha/beta and gamma interferon receptors. 760 46

To evaluate if exhaustion after maximal exercise suppresses the immune system; ten healthy male oarsmen (maximal oxygen uptake, 5.7 +/- 0.2 l.min-1; mean and SE) performed a six minute "all-out" bout on a rowing ergometer (394 +/- 12 watt). Rowing increased the blood leucocyte count as reflected in the concentrations of lymphocytes, monocytes, and neutrophils. Two hours after rowing the leucocyte and neutrophil numbers remained elevated, while the lymphocyte count decreased below the prevalue. The concentrations of cluster designation CD3+ (pan T), CD4+ (T subset), CD8+ (T subset), CD19+ (B cells), and CD16+ natural killer (NK) cells increased during rowing with the elevation in CD16+ cells being sevenfold. Only the concentration of CD3+ and CD8+ cells decreased below prevalues two hours after exercise. The lymphokine activated killer (LAK) cell activity of blood mononuclear cells (BMNC), and the NK cell activity of BMNC (%lysis per fixed number of BMNC), either unstimulated or stimulated with interleukin-2, interferon-alfa or indomethacin, also increased in response to rowing, and returned to the prevalues after two hours. In contrast, the BMNC proliferative responses did not change significantly. The evaluation of NK and LAK cell activities, and the proliferative responses of BMNC suggest that six minute maximal exercise does not suppress the immune response during recovery, even when a large muscle mass is involved.
 ...
PMID:Lymphocyte, NK and LAK cell responses to maximal exercise. 877 78

The aim of this study was to investigate whether moderate or exhaustive endurance exercise influences cytokine levels in whole-blood culture supernatants after stimulation. Therefore, eight healthy subjects were first exposed to moderate exercise on a cycle ergometer for 30 min at 70% of their 4-mmol/l lactic acid (anaerobic) threshold, and 1 week later to exhaustion (for 90 min) at their anaerobic threshold. Blood samples were taken before, 30 min after and 24 h after each exercise bout. The following lymphocyte subpopulations were determined: CD14-positive(+)/CD45+, CD4+, CD8+, and CD16+. Cytokine levels in the supernatants were measured by enzyme-linked immunosorbent assay (ELISA). Production of interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha were induced with lipopolysaccharides (LPS), and that of IL-2 and interferon (IFN)-gamma with staphylococcal enterotoxin B (SEB) and phytohaemagglutinin (PHA). Cortisol levels were also determined by ELISA. The lymphocyte subset distribution was observed to be unchanged after moderate exercise. Thirty minutes after exhaustive exercise, the CD16+ count was found to be significantly lower, whereas 24 h later the CD4+ count was significantly higher than pre-exercise counts. Moderate exercise influenced the IFN-gamma production (PHA-stimulated), which increased significantly from 974 (391) pg/ml before exercise to 1450 (498) pg/ml 24 h later. Thirty minutes after exhaustive exercise the IFN-gamma level in the supernatants (SEB-stimulated) was significantly decreased (from 14470 (11840) pg/ml before exercise to 6000 (4950) pg/ml after exercise). The IL-1beta and TNF-alpha production per monocyte was also significantly reduced.
 ...
PMID:Moderate and exhaustive endurance exercise influences the interferon-gamma levels in whole-blood culture supernatants. 927 75

Aplastic anemia may be associated with persistent viral infections that result from failure of the immune system to control virus. To evaluate the effects on hematopoiesis exerted by sustained viral replication in the presence of activated T cells, blood values and bone marrow (BM) function were analyzed in chronic infection with lymphocytic choriomeningitis virus (LCMV) in perforin-deficient (P0/0) mice. These mice exhibit a vigorous T cell response, but are unable to eliminate the virus. Within 14 d after infection, a progressive pancytopenia developed that eventually was lethal due to agranulocytosis and thrombocytopenia correlating with an increasing loss of morphologically differentiated, pluripotent, and committed progenitors in the BM. This hematopoietic disease caused by a noncytopathic chronic virus infection was prevented by depletion of CD8+, but not of CD4+, T cells and accelerated by increasing the frequency of LCMV-specific CD8+ T cells in T cell receptor (TCR) transgenic (tg) mice. LCMV and CD8+ T cells were found only transiently in the BM of infected wild-type mice. In contrast, increased numbers of CD8+ T cells and LCMV persisted at high levels in antigen-presenting cells of infected P0/0 and P0/0 x TCR tg mice. No cognate interaction between the TCR and hematopoietic progenitors presenting either LCMV-derived or self-antigens on the major histocompatibility complex was found, but damage to hematopoiesis was due to excessive secretion and action of tumor necrosis factor (TNF)/lymphotoxin (LT)-alpha and interferon (IFN)-gamma produced by CD8+ T cells. This was studied in double-knockout mice that were genetically deficient in perforin and TNF receptor type 1. Compared with P0/0 mice, these mice had identical T cell compartments and T cell responses to LCMV, yet they survived LCMV infection and became life-long virus carriers. The numbers of hematopoietic precursors in the BM were increased compared with P0/0 mice after LCMV infection, although transient blood disease was still noticed. This residual disease activity was found to depend on IFN-gamma-producing LCMV-specific T cells and the time point of hematopoietic recovery paralleled disappearance of these virus-specific, IFN-gamma-producing CD8+ T cells. Thus, in the absence of IFN-gamma and/or TNF/LT-alpha, exhaustion of virus-specific T cells was not hampered.
 ...
PMID:Aplastic anemia rescued by exhaustion of cytokine-secreting CD8+ T cells in persistent infection with lymphocytic choriomeningitis virus. 960 30

Recent studies have demonstrated that the expression of Fas by peripheral T cells from HIV-1+ patients is deregulated and increases the susceptibility of these cells to undergo apoptosis. Here, we show that secretion of Fas-ligand (L), the complementary agonist of Fas, is abnormally upregulated in CD4+ cells from HIV-1-infected individuals, particularly during the non-lymphopenic stages of the disease. An increase of soluble Fas-L occurred in T cell cultures from 26 patients with a number of CD4+ cells higher than 400/microliter, whereas it was almost undetectable in cultures from 21 severely lymphopenic patients (CD4+ < 200/microliter). The MTT test, cytofluorimetric analysis of cellular DNA, cytotoxicity, and proliferative assays using the Fas-transfected WC8 mouse lymphoma confirmed the cytocidal capability of T cell supernatants from non-lymphopenic patients. Double-fluorescence analysis revealed that the majority of CD4+ cells (approximately 90%) in these cultures secreted Fas-L in the presence of high intracellular gamma-interferon and low Bcl-2. In contrast, the CD8+/Fas-L+ population was comparably decreased (approximately 55%). Molecular cloning of Fas-L revealed a substantial expression of Fas-L mRNA in cells from non-lymphopenic patients compared with patients with advanced disease and healthy controls. Since CD4+ cells of Th1 phenotype are impaired during HIV-1 infection and show high cellular expression of Fas-L, it is conceivable that excess Fas-L during the early or non-lymphopenic phase of the disease increases the extent of apoptosis in these cells by the Fas/Fas-L pathway. The defective expression of the ligand in severely lymphopenic stages could be explained by exhaustion of this mechanism as the disease progresses.
 ...
PMID:Functional Fas-ligand expression on T cells from HIV-1-infected patients is unrelated to CD4+ lymphopenia. 987 94


1 2 3 4 5 6 7 8 9 10 Next >>