Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pathological induced changes in beta-adrenoceptor function occur in diseases such as asthma and hypertension. The mechanism(s) of this dysfunction is at present unclear. In the present study, the effect of lymphokines on beta-adrenoceptor agonist induced cAMP production in peripheral blood mononuclear cells (PBMC) is investigated. Pre-incubation of PBMC during 20 h with interleukin-2 (IL-2, 100 u ml-1) and granulocyte/macrophage-colony stimulating factor (GM-CSF, 100 u ml-1) significantly decreases beta-adrenoceptor agonist induced cAMP production by 35 +/- 8% and 37 +/- 11% respectively. IL-3 and IL-4 do not affect beta-adrenoceptor agonist induced cAMP production in PBMC. It can be concluded that IL-2 and GM-CSF, mediators derived from T-lymphocytes, can induce beta-adrenoceptor dysfunction in PBMC.
 ...
PMID:Effect of lymphokines on beta-adrenoceptor function of human peripheral blood mononuclear cells. 217 22

A murine IgG1 antibody specific for the IL-2-binding site on the human lymphocyte IL-2 receptor beta chain (CD25) was evaluated in 11 patients who developed acute graft-versus-host disease following allogeneic marrow transplantation. All patients had received cyclosporine and methotrexate for prophylaxis of GVHD, either alone (4 cases), or in combination with antithymocyte globulin (4 cases) or with prednisone (3 cases). Patients had developed GVHD at 7-53 days (median 12) after transplantation and had failed treatment with corticosteroids for 3-44 days (median 19). Residual GVHD was of grade II severity in 4 patients, grade III in 5 patients, and grade IV in 2 patients. Sequential patients received monoclonal antibody in escalating doses from 0.1 mg/kg/day to 1.0 mg/kg/day for 7 days. Side effects were fever, respiratory distress, hypertension, hypotension, and chills occurring in 11 of 72 (14%) antibody infusions. Trough antibody levels greater than 6 micrograms/ml were achieved in patients treated with 0.5 or 1.0 mg/kg/day. Four of eight evaluable patients had an IgM antibody response, and one had an IgG response to the murine immunoglobulin. Clinical response of GVHD was evaluated in 10 patients who received the entire course of the antibody treatment. Among 7 patients treated within 40 days from transplantation, one patient had a complete response in the skin as the only involved organ, and 3 patients had a partial response, 2 in the skin and one in the gastrointestinal tract. No responses were achieved with liver disease at anytime or in any organ in patients treated beyond 40 days after transplantation. Since administration of this antibody was well tolerated and some efficacy was observed in patients with acute GVHD treated early after transplantation, there is a rationale for testing this antibody as an agent for prophylaxis of GVHD.
 ...
PMID:A phase I-II study evaluating the murine anti-IL-2 receptor antibody 2A3 for treatment of acute graft-versus-host disease. 236 50

Serum soluble interleukin 2 receptor (IL-2 R) was determined by the ELISA method in 29 cases of IgA nephropathy and 50 healthy controls. The results showed that the value in IgA nephropathy cases was significantly higher than that in healthy controls. Furthermore, among the cases of IgA nephropathy, the value was significantly higher in the groups with hypertension, elevated serum IgA and depressed creatinine clearance than in that of the corresponding controls. These findings suggest that serum soluble IL-2 R can serve as a prognostic index of IgA nephropathy.
 ...
PMID:Serum soluble interleukin 2 receptor in patients with IgA nephropathy. 263 44

The studies were carried out to compare the effects of food restriction and/or treadmill exercise on the development of high blood pressure and to compare immune function in spontaneously hypertensive rats (SHR). The results demonstrate that moderate food restriction from weaning or a regular treadmill exercise not only maintains significantly lower blood pressure, but also increases T-cell proliferative response against mitogens which is found to be significantly depressed in SHR fed ad libitum. A significant loss of T-cell subpopulation such as W3/25+ T helper cells and OX8+ non-helper T-cells occurring in mice fed ad libitum were restored to normal levels, including IL-2 response, in food-restricted SHR. Our results suggest that both food restriction and/or physical exercise is effective in modulating the blood pressure and increasing T-cell immune functions in SHR.
 ...
PMID:Reduction of blood pressure and restoration of T-cell immune function in spontaneously hypertensive rats by food restriction and/or by treadmill exercise. 349 Dec

Recombinant interleukin (IL)-2 is a newly approved immunoregulatory protein produced by lymphocytes that exhibits a wide range of immunologic effects. It is a true biologic response modifier in that is has no known direct antitumor activity, but mediates its cytotoxicity through activation of effector cells including T cells, natural killer cells, and lymphokine-activated killer cells. Recombinant IL-2 has demonstrated activity in patients with renal cell carcinoma and melanoma, with objective response rates of approximately 15-20%. The median duration of response in renal cell carcinoma is 23 months. Toxicity experienced with high-dose IL-2 can be significant. The most common dose-limiting toxicities are hypertension, weight gain, oliguria, respiratory insufficiency, and neurotoxicity. These effects are generally manageable and reversible on discontinuation of therapy. Administration of low-dose IL-2 has emerged as a means of substantially reducing toxicity. At least in renal cell carcinoma, it appears that the response rate to low-dose IL-2 is comparable to that with higher dosages.
 ...
PMID:Recombinant interleukin-2. 788 67

Immunosuppressants such as cyclosporine are considered to constrain cell growth by preventing the production of growth stimulatory cytokines (e.g., interleukin-2). The possibility exists, however, that CsA and other immunosuppressants might restrain cell growth by promoting the production of growth-inhibitory cytokines. We have explored herein the hypothesis that CsA stimulates the production of transforming growth factor-beta (TGF-beta), and restrains new DNA synthesis in mammalian cells via a TGF-beta-dependent mechanism. To investigate this new postulate independently of an IL-2-dependent mechanism, we utilized, as probes, two mammalian cell lines, distinguished by their sensitivity to growth inhibition by TGF-beta and resistance to IL-2: CCL-64 mink lung epithelial cells (CCL-64 cells) and A-549 human adenocarcinoma cells (A-549 cells). Our experimental approach revealed the following: (A) CsA and not cyclosporine H, an inactive analogue of CsA, mediates growth inhibition of TGF-beta-sensitive cells, CCL-64 cells, and A-549 cells; (B) CsA stimulates these mammalian cells to secrete TGF-beta; and (C) TGF-beta induced by CsA is biologically active in inducing cell growth inhibition (demonstrated by the reversal of CsA-associated inhibition with anti-TGF-beta monoclonal antibodies). Our observations suggest that CsA can regulate cell growth via a TGF-beta-dependent mechanism. Since the multifunctional cytokine TGF-beta can enhance extracellular matrix accumulation as well as augment endothelin production, our findings also advance a mechanism that links, via TGF-beta, the beneficial (immunosuppression) and the harmful (fibrosis, hypertension) consequences of CsA usage.
 ...
PMID:Regulation of new DNA synthesis in mammalian cells by cyclosporine. Demonstration of a transforming growth factor beta-dependent mechanism of inhibition of cell growth. 811 45

Strategies of cell depletion were pursued to extend understanding of the functions of natural killer (NK) cell-like large granulated lymphocytes found in the rodent uterus during pregnancy. Repeated infusions of antibody to Ly-49G2, a surface marker thought to be expressed by the progenitor forms of these cells, removed Ly-49G2+ cells from the virgin but not the pregnant uterus. Large granulated uterine lymphocytes also differentiated during pregnancy in transgenic mice that carried a deletion in the IL-2 gene. This cell population was absent in two strains of mice, p56lck-/lck-.IL-2Rbeta-/IL-2Rbeta- and TgE26. Implantation sites in both of these strains had histopathological anomalies in the zone of decidualization. In TgE26 mice, a sudden onset of fetal loss began at Day 10 of gestation. Fetal death was associated with progressive changes in the maternal uterine arterioles, suggestive of localized arteriosclerosis associated with hypertension. TgE26 females carried immune-competent fetuses to term, apparently through preventive or compensatory mechanisms that may modify the uterine vasculature after the onset of vascular pathology. These studies are the first to suggest a vital role for large granulated lymphocytes in the promotion of fetal survival and pregnancy success.
 ...
PMID:Absence of natural killer cells during murine pregnancy is associated with reproductive compromise in TgE26 mice. 900 46

The past decade has witnessed enormous progress in our understanding of the nature of this process. The development of an atherosclerotic plaque is a complex process which begins with endothelial dysfunction, the trigger for which are factors such as hypercholesterolemia, smoking, hypertension, hyperhomocysteinemia and impaired glucose metabolism. This dysfunction includes increased endothelial permeability to lipoproteins and other plasma constituents, which is mediated by NO, PDGF, prostacyclin, angiotensin II and endothelin; up-regulation of endothelial adhesion molecules including VCAM-1, ICAM-1, and selectins and migration of leukocytes and monocytes-macrophages in the subendothelial space mediated by oxidized LDL, MCP-1, PDGF and MCSF. The next step includes smooth-muscle cells migration (stimulated by PDGF and TGF-beta), T-cell activation (mediated by TNF-alpha and IL-2), formation of foam-cells from macrophages (mediated by oxidized LDL, MCSF, TNF-alpha and IL-1) and platelet adherence and aggregation (stimulated by thromboxane A2, tissue factor etc). The smooth muscle cells form a fibrous cap which confers mechanical stability of the plaque and separates the lipid rich thrombogenic core from the lumen and circulating blood. Whether a plaque will remain intact and therefore stable or rupture and lead to thrombosis causing an acute coronary syndrome (MI, unstable angina pectoris) depends upon a number of factors, the most important of which is its composition. Plaque size plays only a minor role in determining risk of an acute coronary syndrome. Rupture of the fibrous cap occurs due to thinning of the cap caused by an influx and activation of macrophages which release metalloproteinases and other proteolytic enzymes (stimulated by inflammatory cells, particularly T-lymphocytes). These enzymes cause degradation of the fibrous tissue of the cap which can result in thrombous formation and occlusion of the artery. Stable plaques have a thick fibrous cap, a small lipid core, and few inflammatory cells. In contrast, vulnerable plaques have a high lipid content, numerous inflammatory cells, and a thin fibrous cap with reduced collagen and vascular smooth muscle cells in it. Although vulnerable plaques are believed to account for only a small number of all coronary atheromas, they are responsible for most acute coronary events.
 ...
PMID:[New information on the pathophysiology of atherosclerosis]. 1137 94

The anti-interleukin-2 receptor (anti-IL-2R) antibody therapy is an exciting approach to the prevention of acute rejection after renal allograft transplantation whereby immunosuppression is exerted by a selective and competitive inhibition of IL-2-induced T cell proliferation, a critical pathway of allorecognition. The anti-IL-2R antibodies specifically block the alpha-subunit of the IL-2R on activated T cells, and prevent T cell proliferation and activation of the effector arms of the immune system. The anti-IL-2R antibodies are used as induction therapy, immediately after renal transplantation, for prevention of acute cellular rejection in children and adults. During acute rejection, the IL-2Ralpha chain is no longer expressed on T cells; thus, the antibodies cannot be used to treat an existing acute rejection. Two anti-IL-2R monoclonal antibodies are currently in clinical use: daclizumab and basiliximab. In placebo-controlled phase III clinical trials in adults, daclizumab and basiliximab in combination with calcineurin inhibitor-based immunosuppression, significantly reduced the incidence of acute rejection and corticosteroid-resistant acute rejection without increasing the risk of infectious or malignant complications, and neither antibody was associated with the cytokine-release syndrome. Children who receive calcineurin inhibitors and corticosteroids for maintenance immunosuppression, as well as children who receive augmented immunosuppression to treat acute rejection, are at increased risk of growth impairment, hypertension, hyperlipidemia, lymphoproliferative disorders, diabetes mellitus, and cosmetic changes. In older children, the cosmetic adverse effects frequently reduce compliance with the treatment, and subsequently increase the risk of allograft loss. Being effective and well tolerated in children, the anti-IL-2R antibodies reduce the need for calcineurin inhibitors while maintaining the overall efficacy of the regimen; thus, the anti-IL-2R antibodies increase the safety margin (less toxicity, fewer adverse effects) of the baseline immunosuppression. Secondly, the anti-IL-2R antibodies decrease the need for corticosteroids and muromonab CD3 (OKT3) in children as a result of decreased incidence of acute rejection. The recommended pediatric dose of daclizumab is 1 mg/kg intravenously every 14 days for five doses, with the first dose administered within 24 hours pre-transplantation. This administration regimen maintains daclizumab levels necessary to completely saturate the IL-2Ralpha (5-10 microg/mL) in children for at least 12 weeks.The recommended pediatric dose of basiliximab for recipients <35 kg is 10 mg, and 20 mg for recipients > or =35 kg, intravenously on days 0 and 4 post-transplantation. This administration regimen maintains basiliximab levels necessary to completely saturate the IL-2Ralpha (>0.2 microg/mL) in children for at least 3 weeks.
 ...
PMID:Anti-interleukin-2 receptor antibodies for the prevention of rejection in pediatric renal transplant patients: current status. 1451 Jun 27

NK cells are a key component of innate immune systems, and their activity is regulated by cytokines and hormones. Adiponectin, which is secreted from white adipose tissues, plays important roles in various diseases, including hypertension, cardiovascular diseases, inflammatory disorders, and cancer. In this study the effect of adiponectin on NK cell activity was investigated. Adiponectin was found to suppress the IL-2-enhanced cytotoxic activity of NK cells without affecting basal NK cell cytotoxicity and to inhibit IL-2-induced NF-kappaB activation via activation of the AMP-activated protein kinase, indicating that it suppresses IL-2-enhanced NK cell cytotoxicity through the AMP-activated protein kinase-mediated inhibition of NF-kappaB activation. IFN-gamma enhances NK cell cytotoxicity by causing an increase in the levels of expression of TRAIL and Fas ligand. The production of IFN-gamma, one of the NF-kappaB target genes in NK cells, was also found to be suppressed by adiponectin, accompanied by the subsequent down-regulation of IFN-gamma-inducible TRAIL and Fas ligand expression. These results clearly demonstrate that adiponectin is a potent negative regulator of IL-2-induced NK cell activation and thus may act as an in vivo regulator of anti-inflammatory functions.
 ...
PMID:Adiponectin is a negative regulator of NK cell cytotoxicity. 1667 Mar 4


1 2 3 4 5 Next >>