Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The combination therapy with natural type human tumor necrosis factor (n-TNF; MHR-24) and human lymphoblastoid interferon-alpha (n-IFN-alpha; MOR-22) was investigated for antitumor effect against renal cell carcinoma in a multiclinic cooperative study throughout Japan. The "Response criteria of Japan Society for Cancer Therapy" were followed for the handling of subjects and the evaluation of antitumor effect. MHR-24 was administered at a daily dosage of 5,000-10,000 JRU by intravenous drip and MOR-22 at a dosage of 5,000,000 IU daily was administered intramuscularly at the same time. Both drugs were administered for 4 weeks or longer. A total of 36 patients were enrolled as subjects in the study. None of them were classified as ineligible. Five patients, were classified as imperfectly evaluable, and 31, as evaluable for the results of treatment. The responses in the evaluable patients were partial response (PR) in 4 patients, minor response (MR) in 3 patients, no change (NC) in 14 patients and progressive disease (PD) in 10 patients, with a response rate of 12.9%. Adverse reactions to the therapy were investigated in all 36 patients. The frequent subjective and objective reactions that occurred were fever, rigors and shivering, anorexia, and generalized malaise, and the frequent abnormal laboratory findings were leukopenia, thrombocytopenia, elevation of GOT, and elevation of GPT.
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PMID:[Combination therapy with natural type human tumor necrosis factor (MHR-24) and human lymphoblastoid interferon-alpha (MOR-22) against renal cell carcinoma--a multiclinic cooperative, early phase II study. Subcommittee on Urogenital Malignancy, Committee on MHR-24 against Tumors]. 148 83

To elucidate the role of tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) in chronic hepatitis type C (CH(C], TNF alpha and IL-1 beta released from peripheral blood mononuclear cells were measured in 6 CH(C) patients before and during interferon therapy. During the therapy, TNF-alpha levels were significantly high in two patients whose serum ALT levels turned normal, while IL-1 beta levels did not show significant change. These results suggest that TNF-alpha takes part in improvement of CH(C).
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PMID:Production of tumor necrosis factor alpha and interleukin 1 beta by peripheral blood mononuclear cells from chronic hepatitis type C patients during interferon therapy. 170 36

BALB/C female mice were given different dosages of TNF in 0.1 ml sterile PBS containing 1% human serum albumin. Control mice were injected with PBS and human albumin alone. Autopsy examination was carried out and blood biochemistry studied. The results showed that the LD50 was 6 X 10(7) mu/kg. There were serious hyperemia and inflammation of the organs of dead mice, while other smaller dosages of TNF caused acute toxicity of different degrees, except for the 3 X 10(6) mu/kg dosage. Changes of alkaline phosphatase were significant compared with control. Blood sugar increases correlated with the TNF dosage. Changes of GPT and BUN were insignificant. TNF levels in the sera of humans and rabbits were also studied following TNF injection. The serum level of TNF decreased rather quickly in both animals and patients: about 85% of TNF was lost within 5 min after TNF injection, and no TNF could be detected 6 hrs after injection.
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PMID:[Studies on acute toxicity and serum level changes of tumor necrosis factor]. 253 78

A Phase I study of rHu-TNF (PT-050) was conducted in patients with various malignant tumors refractory to conventional therapy. rHu-TNF was administered by 30-min intravenous (i.v.) infusion or intratumor (i.t.) injection. The starting dose of 1 X 10(5) U/body was increased to 5 X 10(6) U/body in the i.v. group and to 2 X 10(6) U/body in the i.t. group. rHu-TNF was evaluated in 41 patients among the enrolled 43 patients of the i.v. group, and in 9 out of 10 in the i.t. group. In the i.v. group, fever (68.3%), chills (75.6%), hypotension (46.3%), general fatigue (34.1%), nausea/vomiting (22.0%/22.0%), pain in the extremities (17.1%), etc. were observed as adverse reactions (ADRs), and elevation of GOT/GPT (46.3%/43.9%), elevation of ALP(26.8%)and decrease in platelets (12.2%), etc. were observed as abnormal laboratory findings. Among these, hypotension was recognized as the dose-limiting factor and the maximum tolerated dose was considered to be 1 X 10(6) U/body. Plasma levels of rHu-TNF after 30-min i.v. administration were dose-related, and decreased with half-lives of 0.5-2.4 hours. In the i.t. group, ADRs occurred with a lower incidence than in the i.v. group except for fever, chills and general fatigue. Plasma levels after i.t. administration were all within the assay limit. Evident tissue necrosis was observed in the region where rHu-TNF was administered in the i.t. group.
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PMID:[A phase I study of recombinant human tumor necrosis factor (rHu-TNF: PT-050). The PT-050 Study Group]. 302 81

A phase I study of recombinant human tumor necrosis factor (rHu-TNF:PT-050) given by intravenous infusion over 30 min or by intratumoral administration was performed in 53 patients with various types of malignant tumors. The dose of rHu-TNF was started with 0.1 x 10(6) U/body for both intravenous infusion and intratumoral administration and increased to 5 x 10(6) U/body for intravenous infusion and 2 x 10(6) U/body for intratumoral administration. The side effects of rHu-TNF given by intravenous infusion included fever, shaking chills, hypotension, general malaise, nausea, and vomiting, and clinical laboratory tests showed elevations of GOT, GPT, and ALP, etc. Among these, only hypotension was dose-related and was considered to be a dose-limiting factor. The maximum tolerable dose estimated was 1 x 10(6) U/body. The plasma concentration of rHu-TNF after completion of a 30-min infusion was dose-dependent, and the elimination half-life was 0.5-2.4 hr. When the rHu-TNF was administered intratumorally, the frequency of side effects was low compared with intravenous infusion.
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PMID:Phase I study of recombinant human tumor necrosis factor (rHu-TNF:PT-050). 318 Jan 46

Intravenous administration of a single dose (100 micrograms/kg bw) of recombinant tumour necrosis factor-alpha (TNF, cachectin) to rats increased the rate of in vitro fatty acid synthesis in interscapular brown adipose tissue (IBAT) from both glucose and alanine, without changes in the oxidation of these substrates to 14CO2. Lactate production and glycerol release were also unaffected by treatment with the cytokine. Additionally, the presence of TNF in the incubation media did not affect fatty acid synthesis, suggesting an indirect effect of the cytokine. The activities of different enzymes of glucose and alanine metabolism such as hexokinase, phosphofructokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase and alanine transaminase, did not suffer changes as a consequence of TNF administration. The same applied to the enzymatic activities involved in fatty acid synthesis such as fatty acid synthase, acetyl-CoA carboxylase and ATP-citrate lyase. Conversely, citrate levels in IBAT were increased in animals treated with TNF, suggesting that it could be the cause for the increased fatty acid synthesis in this tissue.
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PMID:Metabolic effects of tumour necrosis factor-alpha on rat brown adipose tissue. 759 46

Tumor necrosis factor alpha (TNF alpha) was measured with an enzyme-linked immunosorbent assay. TNF alpha levels in peripheral blood of patients with twenty-one cases of chronic persistent hepatitis (7.3 +/- 9.5 micrograms/L), fourty-two cases of chronic active hepatitis (15.4 +/- 31.1 micrograms/L), one hundred and six cases of liver cirrhosis (11.1 +/- 17.7 micrograms/L) and one hundred and ten cases of parimary hepatocellular carcinoma (10.9 +/- 13.3 micrograms/L) was significantly increased when compared with normal controls (4.3 +/- 2.9 micrograms/L) (P < 0.01). There was significant correlation between tumor necrosis factor alpha levels and ALT elevation and also between TNF alpha levels and bilirubin contents more than 100 mumol/L in chronic hepatitis patients. Tumor necrosis factor alpha levels was also significantly in HBV concomitant with HCV and/or HDV infection than in HBV infection alone. There was no correlation in tumor necrosis factor alpha levels and AFP concentrations. These findings show that tumor necrosis factor participates in the activity process of liver disease.
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PMID:[Tumor necrosis factor alpha levels in patients with chronic liver diseases and its relationship to pathogenesis]. 771 14

The following study was performed to determine the effects of phosphodiesterase IV (PDE-IV) inhibition and its attenuation of tumor necrosis factor (TNF alpha) production in a rat model of the Adult Respiratory Distress Syndrome (ARDS). Rats were either unexposed (n = 8), pretreated orally with vehicle prior to intratracheal saline exposure (n = 11), pretreated with vehicle prior to 7 mg/kg intratracheal endotoxin (LPS) administration (n = 22), or pretreated with 5 or 50 mg/kg rolipram prior to LPS exposure (n = 6 and 7, respectively). Blood was sampled 1 and 3 hr post LPS exposure and assayed for plasma TNF alpha concentrations. Twenty-four hours after LPS exposure, blood was sampled again for hematologic measurements. The rats were then anesthetized and exsanguinated. Bronchoalveolar lavage (BAL) was performed after the lung of each rat was removed and weighed. Rolipram pretreatment was protective against LPS-induced mortality and also resulted in reduced plasma TNF alpha concentrations. LPS induced pulmonary edema, as indicated by wet/dry lung weight ratio (W/D) and total BAL protein content (TP) was attenuated by rolipram pretreatment. LPS-induced alveolar hemorrhage was reduced by rolipram pretreatment, but LPS-induced pulmonary neutrophilia was not. The hemoconcentration induced by LPS was reduced by rolipram, as was the LPS-induced thrombocytopenia. However, LPS-induced changes in circulating leukocyte populations were actually exacerbated by rolipram. LPS-induced alterations in renal and hepatic function, indicated by increased blood urea nitrogen (BUN), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), were inhibited by rolipram.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Therapeutic intervention in a rat model of ARDS: IV. Phosphodiesterase IV inhibition. 838 94

The two apoptosis receptors of mammalian cells, i.e. the 55 kDa TNF receptor (TNF-R1) and CD95 (Fas/APO1) are activated independently of each other, however, their signaling involves a variety of ICE-related proteases [I]. We used a cell-permeable inhibitor of ICE-like protease activity to examine in vivo whether post-receptor signaling of TNF and CD95 are fully independent processes. Mice pretreated with the inhibitor, Z-VAD-fluoromethylketone (FMK) were dose-dependently protected from liver injury caused by CD95 activation as determined by plasma alanine aminotransferase and also from hepatocyte apoptosis assessed by DNA fragmentation (ID50 = 0.1 mg/kg). A dose of 10 mg/kg protected mice also from liver injury induced by TNF-alpha. Similar results were found when apoptosis was initiated via TNF-alpha or via CD95 in primary murine hepatocytes (IC50 = 1.5 nM) or in various human cell lines. In addition to prevention, an arrest of cell death by Z-VAD-FMK was demonstrated in vivo and in vitro after stimulation of apoptosis receptors. These findings show in vitro and in vivo in mammals that CD95 and the TNF-alpha receptor share a distal proteolytic apoptosis signal.
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PMID:ICE-protease inhibitors block murine liver injury and apoptosis caused by CD95 or by TNF-alpha. 909 74

Liver ischemia and reperfusion injury is mediated by oxygen free radicals, cytokines, and prostanoids produced by Kupffer cells and infiltrating neutrophils. Fish oil-supplemented diets alter membrane phospholipid composition and modify prostanoids and cytokine production in response to ischemia and reperfusion. This study tested the hypothesis that a fish oil-supplemented diet would attenuate warm liver ischemia and reperfusion injury in the rat. Male Sprague-Dawley rats were fed Vital HN supplemented with either fish oil (FO) or corn oil (CO) by the continuous duodenal infusion for 5 days. Total dietary fat (26% of total calories), caloric intake (70 cal/day), and volume (60 ml/day) were identical between two groups. Plasma eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels increased significantly in rats fed fish oil (0 to 16.3% for EPA and 2 to 12% for DHA). Liver histology was similar in both groups before ischemia. On Day 6, rats were subjected to 60 min of reversible hepatic ischemia. Plasma TNF levels, 1 and 24 hr after reperfusion, were not different between FO and CO rats. Liver injury assessed by bile flow, histology, plasma ALT, and bile glutathione efflux did not differ between groups. We conclude that our fish oil-supplemented enteral diet does not attenuate warm liver ischemia and reperfusion injury in rats.
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PMID:Fish oil-supplemented feeding does not attenuate warm liver ischemia and reperfusion injury in the rat. 927 Dec 78


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