Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0235394 (wasting)
 8,040 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Increased release of tumour necrosis factor is thought to contribute to human-immunodeficiency-virus-associated wasting syndrome. Elevated serum concentrations of tumour necrosis factor have, however, mainly been found during acute opportunistic infections and were not correlated with the degree of wasting. This finding may be explained by the paracrine release and the rapid inactivation of tumour necrosis factor. Serum levels of the two recently detected soluble tumour necrosis factor receptor proteins (p55 and p75) are assumed to reflect tumour necrosis factor release. 2. Serum levels of soluble tumour necrosis factor receptors 55 and 75 were measured by an enzyme-linked immunological and biological binding assay in 45 human-immunodeficiency-virus-infected patients and seven healthy control subjects. Patients were followed up for survival. Serum albumin, prealbumin, total iron-binding capacity (transferrin) and C-reactive protein concentrations were measured using standard laboratory methods. Body composition was determined by bioelectrical impedance analysis. 3. Serum concentrations of soluble tumour necrosis factor receptor 55 and 75 were both significantly increased in human-immunodeficiency-virus-infected patients as compared with the health control subjects (P < 0.05); soluble tumour necrosis factor receptor concentrations were even more increased in patients with elevated C-reactive protein levels (> or = 5mg/l) as compared with those with normal C-reactive protein levels (< 5mg/l; P < 0.0001 and P < 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Tumour necrosis factor receptor levels are linked to the acute-phase response and malnutrition in human-immunodeficiency-virus-infected patients. 816 42

To evaluate the biologic potential of T cell-specific TNF production in vivo, we have generated transgenic mice constitutively expressing TNF in their T cell compartment. This was achieved by placing a wild-type or a 3'-UTR modified fragment of the human TNF gene under the influence of the T cell-specific, locus control region of the human CD2 gene. Transgenic mice that express human TNF mRNA in T cells develop marked histologic and cellular changes locally in their lymphoid organs and a lethal wasting syndrome associated with widespread vascular thrombosis and tissue necrosis. The extent of pathologic changes and their time of onset appear to reflect levels of transgene expression. Thus, transgenic lines that express the transgene at high levels show both lymphoid organ and systemic abnormalities with wasting. In one transgenic line, mice express lower levels of the transgene and develop normally despite pronounced local lymphoid organ defects, confirming in vivo, the differential potential of localized and systemic TNF action. All pathologic changes could be neutralized by the administration of mAb specific for human TNF. These results demonstrate the important role of T cell-specific TNF production in the development of specific pathology and provide a means by which to evaluate the role of TNF in thymocyte development. Transgenic mice that express TNF constitutively in the T cell compartment offer a unique in vivo system by which to analyze the molecular character of systemic vs contact-dependent and paracrine modes of TNF action. Furthermore, given the species-specific nature of the mouse p75 TNF receptor, it is assumed that the pathology induced by human TNF in these transgenic mice is associated exclusively with p55 TNF receptor signaling. Conceivably, the differential contribution of each of the two TNF receptors in thymus development and TNF-mediated disease can be assessed by comparison of the biologic potential of human vs mouse TNF in the transgenic system developed.
 ...
PMID:Wasting, ischemia, and lymphoid abnormalities in mice expressing T cell-targeted human tumor necrosis factor transgenes. 834 87

Chronic inflammatory diseases are associated with increased soluble tumour necrosis factor (TNF) receptor concentrations in serum. To obtain such an increase, we implanted mice with ethylene vinyl-acetate or poly (lactic-co-glycolic) acid copolymers containing human soluble p55 TNF receptor. Copolymers containing rather small amounts of the receptor (about 20 micrograms) maintained prolonged increases in serum receptor concentrations. Mice implanted with these copolymers were effectively protected against lethal wasting and from arthritis resulting from chronic exposure to TNF. These findings suggest that the increased production of soluble TNF receptors in chronic inflammatory diseases counteracts deleterious effects of TNF, and suggest a therapeutic application for the natural forms of the receptors in such diseases.
 ...
PMID:Long-term protection against the effects of tumour necrosis factor by controlled delivery of the soluble p55 TNF receptor. 881 45

Estrogen deficiency induces bone loss by upregulating osteoclastogenesis by mechanisms not completely defined. We found that ovariectomy-enhanced T-cell production of TNF-alpha, which, acting through the TNF-alpha receptor p55, augments macrophage colony-stimulating factor-induced (M-CSF-induced) and RANKL-induced osteoclastogenesis. Ovariectomy failed to induce bone loss, stimulate bone resorption, or increase M-CSF- and RANKL-dependent osteoclastogenesis in T-cell deficient mice, establishing T cells as essential mediators of the bone-wasting effects of estrogen deficiency in vivo. These findings demonstrate that the ability of estrogen to target T cells, suppressing their production of TNF-alpha, is a key mechanism by which estrogen prevents osteoclastic bone resorption and bone loss.
 ...
PMID:Estrogen deficiency induces bone loss by enhancing T-cell production of TNF-alpha. 1108 20

In vivo studies have shown T cells to be central to the mechanism by which estrogen deficiency induces bone loss, but the mechanism involved remains, in part, undefined. In vitro, T cells from ovariectomized mice produce increased amounts of tumor necrosis factor (TNF), which augments receptor activator of NF-kappa B ligand (RANKL)-induced osteoclastogenesis. However, both the mechanism and the relevance of this phenomenon in vivo remain to be established. In this study, we found that ovariectomy increased the number of bone marrow T cell-producing TNF without altering production of TNF per T cell. Attesting to the essential contribution of TNF, ovariectomy induced rapid bone loss in wild type (wt) mice but failed to do so in TNF-deficient (TNF(-/-)) mice. Furthermore, ovariectomy induced bone loss, which was absent in T cell-deficient nude mice, was restored by adoptive transfer of wt T cells, but not by reconstitution with T cells from TNF(-/-) mice. These findings demonstrate the key causal role of T cell-produced TNF in the bone loss after estrogen withdrawal. Finally, ovariectomy caused bone loss in wt mice and in mice lacking p75 TNF receptor but failed to do so in mice lacking the p55 TNF receptor. These findings demonstrate that enhanced T cell production of TNF resulting from increased bone marrow T cell number is a key mechanism by which estrogen deficiency induces bone loss in vivo. The data also demonstrate that the bone-wasting effect of TNF in vivo is mediated by the p55 TNF receptor.
 ...
PMID:Up-regulation of TNF-producing T cells in the bone marrow: a key mechanism by which estrogen deficiency induces bone loss in vivo. 1171 53

Adjuvant-induced arthritis is associated with body weight loss and decreased pituitary growth hormone (GH) and hepatic insulin-like growth factor-I (IGF-I) synthesis. Cytokines as tumor necrosis factor (TNF) mediate wasting associated with chronic inflammation. The aim of this study was to analyse whether the inhibition of TNF is able to revert the decrease in the body weight and the GH/IGF-I axis in arthritic rats. Male Wistar rats were injected with Freund's adjuvant, and 15 days later arthritic and control rats were daily injected with polyethylene glycol linked to soluble TNF receptor p55 (PEG-sTNFRI) (1 mg/kg, s.c.) or saline for 8 days. There was a significant decrease in pituitary GH mRNA (P<0.05), hepatic IGF-I mRNA (P<0.01) and serum concentrations of IGF-I (P<0.01) in arthritic rats. The 8-day administration of PEG-sTNFRI resulted in an increase in food intake (P<0.05) and body weight gain (P<0.01) in arthritic but not in control rats. There was an increase in pituitary GH mRNA after PEG-sTNFRI treatment both in control and in arthritic rats. There was a significant increase in IGF-I serum concentrations (P<0.05) and hepatic IGF-I mRNA expression (P<0.05) in control rats treated with PEG-sTNFRI, whereas the effect of this anti-TNF agent in arthritic rats was only statistically significant in hepatic IGF-I mRNA expression (P<0.05). These data suggest that TNF seems to be involved in the decrease in GH and IGF-I synthesis in arthritic rats.
 ...
PMID:Anti-tumor necrosis factor agent PEG-sTNFRI improves the growth hormone/insulin-like growth factor-I system in adjuvant-induced arthritic rats. 1654