Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antineoplastic agents affect the healing of intestinal anastomoses. They often induce anorexia and diarrhea, possibly caused by morphological changes in the small intestinal mucosa. These changes were evaluated in the rat ileum. Animals in group I underwent only intestinal surgery while those in groups II and III underwent surgery on the third day of a 5-day course with cisplatin (in two different doses), bleomycin, and 5-fluorouracil. The parameters were: number of mitoses in crypts, crypt depth, villus height, width, and contour length, measured in the mucosa of primarily resected segments of the ileum and of the anastomotic area. Surgery yields an increased crypt depth and villus length in the anastomotic area without changing villus width. The changes in intestinal crypts precede those in villi. Antineoplastic drugs decrease crypt mitotic rate, villus height, width, and contour length. After cessation of antineoplastic chemotherapy mitotic activity increases. The shallower and shorter villi increase in width and length resulting in an increased villus contour length and area. A linear relation exists between villus contour length and villus height and width. Thus, antineoplastic polychemotherapy, dose-dependently, reduces and surgical trauma increases intestinal proliferative activity. However, the morphologic changes do not unequivocally explain possible metabolic disturbances causing retarded intestinal wound healing.
Exp Mol Pathol 1992 Apr
PMID:Morphometric analysis of the effects of antineoplastic drugs on mucosa of normal ileum and ileal anastomoses in rats. 137 68

Eighty previously treated postmenopausal women with metastatic breast cancer were randomized to receive fadrozole (CGS 16 949A), a new aromatase inhibitor, 1 or 4 mg orally per day. Seventy eight patients were evaluable for toxicity and response. Only mild to moderate toxicity, namely hot flushes (28%), nausea and vomiting (13%), fatigue (8%) and loss of appetite (5%) occurred. Complete response was documented in 10% and partial response in 13% of patients with 45% having a no change status for at least 2 months. The median time to treatment failure is 4.1 months. The median survival is 23.7 months. The median survival is 23.7 months. The response and survival in patients with estrogen receptor positive and estrogen receptor unknown disease were not significantly different. Neither response nor survival was significantly different between the patients receiving 1 or 4 mg of fadrozole per day. Fadrozole is a well tolerated, effective second line treatment for women with metastatic breast cancer.
J Steroid Biochem Mol Biol 1992 Sep
PMID:Fadrozole hydrochloride, a new nontoxic aromatase inhibitor for the treatment of patients with metastatic breast cancer. 138 48

A phase II clinical trial was conducted using subcutaneous recombinant human interleukin-2 (rIL-2, EuroCetus) and subcutaneous interferon-alpha 2b (rIFN-alpha 2b, Essex) in patients with advanced cancer. Safety and tolerance of this outpatient regimen were assessed in 17 patients with progressive metastatic renal carcinoma, 14 of whom were evaluable for clinical response to combined rIL-2 and rIFN-alpha 2b. In this study, rIL-2 was administered every 12 hours, at 1.5 million (Cetus) U/m2 on days 1 and 2, followed by 0.3 million U/m2 5 days per week for 6 consecutive weeks. Concomitantly, rIFN-alpha 2b was given as 5 million U/m2 three times weekly for 6 consecutive weeks. Patients presenting with stable or regressive disease after 6 weeks of rIL-2 and rIFN-alpha 2b (11 of 14) were scheduled to repeat combination therapy. After one treatment cycle, five of 14 patients presented with partial remission; two of these patients achieved complete regression of metastatic lesions. After therapy, six patients have been in stable disease for up to 8 months. toxicity of this regimen was moderate, with local inflammation of the injection sites, grade I-II (World Health Organization criteria) fevers, chills, malaise, nausea and/or vomiting, and anorexia in 70% to 100% of patients treated. After 6 weeks of rIL-2 and rIFN-alpha 2b, laboratory evidence of treatment-related hypothyroidism and hyperthyroidism was obtained in one and four patients, respectively. Immunogenicity of sc rIL-2 was mostly limited to the development of nonneutralizing antibodies that occurred in approximately 40% of patients. None of the patients exhibited antibodies specific to rIFN-alpha 2b.
Mol Biother 1990 Sep
PMID:Subcutaneous interleukin-2 and interferon-alpha 2b in patients with metastatic renal cell cancer: the German outpatient experience. 222 98

Satiety means an internal state that leads to termination of eating. We have isolated an anorexigenic glycoprotein (M.W. 50,000 dalton) from human and rat erythrocyte membrane and from rat liver plasma membrane. The substance isolated from all these membrane sources has almost same onset and offset anorectic effect in rats deprived of food for 96 h as well as in normally fed rats without any rebound. Similar properties of membrane anorectic substance and plasma satietin indicated that it has membrane origin. The results also suggest that the loss of appetite in chronic diseases involving damage or turn-over of cell membranes could be due to release of a glycopeptide from cellular membranes into the circulation.
Mol Cell Biochem
PMID:Isolation of an anorexigenic protein from membranes. 262 54

A clinical phase I trial with recombinant human tumor necrosis factor-alpha (rTNF-alpha) was performed in 30 patients with advanced malignancies. The maximal tolerated dose (MTD) by 3 times weekly intramuscular (i.m.) application was 150 micrograms m-2. Main subjective toxicities including chills, fever, hypotension, fatigue, and anorexia were dose-related. In addition, transient changes in hematologic parameters and lipid metabolism were noted. Two out of 25 evaluated patients showed a minor tumor response after eight weeks of therapy. There was evidence for an improvement of in vivo immuneresponsiveness as revealed from positive delayed type hypersensitivity (DTH) skin tests of 3 out of 6 pretherapeutically anergic patients. We conclude from this phase I trial that rTNF-alpha can be safely administered at doses up to 150 micrograms m-2 i.m., 3 times weekly, without evidence of cumulative toxicity in long-term treatment.
Mol Biother 1988
PMID:Phase I study of recombinant human tumor necrosis factor-alpha in patients with advanced malignancies. 326 69

The present investigation was undertaken to determine whether or not there are histochemical and morphological changes in the intestine of the chronically reserpine-treated rat, an animal model of cystic fibrosis. Male Sprague-Dawley rats were given seven daily intraperitoneal injections of reserpine at dosages of 0.5 (n = 6) or 1.0 mg/kg body weight (n = 6). Control groups consisted of parfed solvent-injected (n = 6), solvent-injected (n = 4), and saline-injected animals (n = 4). Light microscopic histochemical procedures and morphological assessments were performed on sections of "Swiss rolls" of small and large intestine. Chronic reserpine treatment caused an increase in the sulfation of goblet cell mucin in the small intestine without accompanying morphological change; these findings resemble those reported in cystic fibrosis. No qualitative differences in mucin were found in the large intestine but there was an increased number of goblet cells in the surface epithelium and retention of mucus within these cells. Similar although less marked changes were noted in the parfed controls suggesting that those observed in the treated groups may be due, in part, to the reserpine-induced anorexia. The resemblance between the changes in the small intestine of the reserpine-treated rat and those observed in CF patients supports the contention that the chronically reserpine-treated rat is suitable as a model of cystic fibrosis.
Exp Mol Pathol 1987 Aug
PMID:Morphological and histochemical changes in intestinal mucosa in the reserpine-treated rat model of cystic fibrosis. 360 43

The autosomal recessive lethal anorexia mutation in mice (anx/anx) causes starvation in preweanlings. In addition, this murine neurodevelopmental mutant shows other distinct phenotypic characteristics and dysfunctional behaviors. Previous studies strongly suggested that the mutation results in elevated serotonergic stimulation, because these traits are characteristic of such overstimulation and because brain serotonin is believed to have an inhibitory effect on feeding behavior. In this report, we show extensive serotonergic hyperinnervation in normal target fields (hippocampus, cortex, olfactory bulb and cerebellum) of mutant mice. Despite the extensive hyperinnervation, the normal laminar organization of the brain was retained. The specificity of the mutation to the serotonergic system was confirmed by demonstration of normal catecholaminergic innervation in the central nervous system (CNS), and this specificity was especially striking in a common target field, the cerebellum. Serotonergic hyperinnervation in these mutant preweanling mice may represent the underlying etiology of increased serotonergic stimulation which leads to anorexic starvation, abnormal behavior, and premature death.
Brain Res Mol Brain Res 1994 Aug
PMID:Drastic and selective hyperinnervation of central serotonergic neurons in a lethal neurodevelopmental mouse mutant, Anorexia (anx). 798 37

Cachexia and anorexia commonly occur in patients with cystic fibrosis (CF), particularly those with severe pulmonary compromise and heavy tracheobronchial colonization with Pseudomonas aeruginosa. Current understanding of the pathophysiology of cachexia attributes much of the anorexia and weight loss to the effects of the cytokine tumor necrosis factor (TNF), which is secreted by endotoxin-stimulated macrophages. It has further been suggested that TNF may play a role in the pathobiochemistry of CF cachexia, secondary to the localized inflammatory response in the lung or wider systemic activation of cells of the monocyte-macrophage series in response to endotoxin. This study investigates TNF production and gene expression by peripheral blood monocyte-derived macrophages from CF patients, compared with normals (NL). The results indicate that although both cell populations responded dose-dependently to lipopolysaccharide (LPS); CF macrophages, upon stimulation with LPS at concentrations of 1 to 1,000 ng/ml, consistently produced substantially higher amounts of TNF than NL macrophages. At the molecular level, Northern blot analysis also revealed that both macrophage populations expressed TNF mRNA in response to LPS in a dose-dependent manner. However, at the same LPS concentrations, CF macrophage TNF mRNA expression was 2- to 4-fold greater than that of NL macrophages. LPS had no effect in either macrophage population on mRNA for CHO-B, a constitutive probe. To investigate differences between NL and CF macrophage TNF regulation, nuclear run-on/half-life studies as well as studies addressing potential differences in LPS membrane interactions and signal transduction were performed.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1993 Nov
PMID:Expression and regulation of tumor necrosis factor in macrophages from cystic fibrosis patients. 821 92

Hunger and satiety are complex interplay of several factors in human and animal species. Reduced food intake has also been observed under various pathological conditions. Earlier, we have been able to isolate an endogenous glycoprotein from erythrocyte membranes, which causes anorexia in rats. In the present study, a similar anorexigenic proteoglycan from Mung bean sprout membranes has been isolated and purified. The proteoglycan (50 kDa) consisted of 70-85% carbohydrate with galactose, glucose galactosamine and mannose as the main sugars. Protein part on analysis showed higher glutamic acid and serine content. This proteoglycan reduces food intake when injected in rats deprived of food for 96 hr as well as normally fed rats, mice and rabbits without any rebound. The TCA-soluble proteoglycan from different plant sources have also been compared for their anorexigenic activity. The similarities observed among plant and animal cell membrane proteoglycans with satietins isolated from human blood plasma could be due to membrane origin of satietins.
Mol Cell Biochem 1993 Mar 24
PMID:A novel plant membrane proteoglycan which causes anorexia in animals. 848 51

Interleukin-1 beta (IL-1 beta) is released during pathophysiological processes. IL-1 beta induces neurological manifestations when administered into the cerebrospinal fluid (CSF) at pathophysiological concentrations detected during central nervous system (CNS) infections and other neurological disorders. In the present study, we investigated the regulation of the IL-1 beta system in the CNS in response to the chronic intracerebroventricular (icv) microinfusion of IL-1 beta at estimated pathophysiological concentrations in the CSF. IL-1 receptor type I (IL-1RI), IL-1 receptor antagonist (IL-1Ra), and IL-1 beta mRNAs were determined by sensitive RNase protection assays in brain target regions for IL-1 beta (cerebellum, parieto-frontal cortex, hippocampus, and midbrain). The results show that chronic icy microinfusion of IL-1 beta induced significant anorexia, increased the cerebellar IL-1RI mRNA content, increased IL-1Ra and IL-1 beta mRNAs levels in the cerebellum > midbrain > cortex > hippocampus, and induced profiles of IL-1RI mRNA, IL-1Ra mRNA, and IL-1 beta mRNA that were highly intercorrelated. On the other hand, levels of rat glyceraldehyde 3-phosphate dehydrogenase mRNA and 18S rRNA were fairly constant, and heat-inactivated IL-1 beta had no effect on food intake or on IL-1RI, IL-1Ra, and IL-1 beta mRNAs levels in any brain region. The data suggest the operation of an IL-1 beta feedback system (IL-1 beta/ IL-1Ra/IL-1RI) in brain regions. Dysregulation of the CNS IL-1 beta feedback system may have pathophysiological significance. This may be reflected, for example, in the pathogenicity and severity of neurological diseases, such as CNS infections.
J Mol Neurosci 1996
PMID:Regulation of brain interleukin-1 beta (IL-1 beta) system mRNAs in response to pathophysiological concentrations of IL-1 beta in the cerebrospinal fluid. 890 13


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