Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four children with lymphoproliferative malignant disease, two with acute lymphocytic leukemia in remission and two with Hodgkin's disease, were treated with a Thymic Hormone, THF, for disseminated varicella infecition. It is suggested that THF increased significantly the number of peripheral blood lymphocytes and T-rosette forming lymphocytes in 3 out of 4 children, who developed the varicella at the time of impaired cellular immunity. On the other hand, in the fourth child, with Hodgkin's disease, who had a normal number of T-rosettes, a decreased absolute number of lymphocytes as well as T-rosettes was observed over a course of 14 days THF treatment, although the percent of T-cells has not changed significantly. All of the four children recovered, including the child who was at high risk, with a marked lymphopenia, severe bilateral pneumonitis, hepatitis secondary infected skin lesions and psudomonas sepsis. It is indicated that THF therapy may restore the depressed cellular immunity in immunosuppressed children with malignant disease, and has its value as a supportive immunotherapy in life-threatening disseminated varicella infection.
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PMID:Thymic hormone (THF) therapy in immunosuppressed children with lymphoproliferative neoplasia and generalized varicella. 26 20

Both cisplatin and leucovorin (LV) interact with fluorouracil (5-FU) by increasing intracellular reduced folate levels and thereby the inhibition of thymidylate synthase. Therefore, the addition of LV to cisplatin and 5-FU (PFL) may increase the activity of that combination in head and neck cancer. We treated 31 patients with locally advanced head and neck cancer with two cycles of neoadjuvant PFL consisting of 100 mg/m2 of cisplatin on day 1 followed by a 5-day continuous infusion of 5-FU at 1,000 mg/m2/day and oral LV at 100 mg administered every 4 hours during the entire duration of chemotherapy infusion. Two patients died during neoadjuvant chemotherapy of sudden death and sepsis, respectively, and were not evaluated for response. Of 29 evaluable patients, nine had a complete response (CR), 17 had a partial response (PR), and three had stable disease. Toxicities consisted of mild to moderate myelosuppression and moderate to severe mucositis, necessitating reduction of 5-FU on cycle 2 to less than or equal to 80% of the intended dose in 22 of 29 patients. Administration of LV by repeated oral dosing resulted in total reduced folate plasma concentrations of 5.3 (+/- 2.9) and 6.7 (+/- 3.4) mumol on days 2 and 4 of the 5-FU infusion. The sum of 1-LV and its metabolite 5-CH3-tetrahydrofolate exceeded the concentration of d-LV, consistent with selective absorption of the biologically active 1-stereoisomer from the gastrointestinal tract.
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PMID:Induction chemotherapy with cisplatin, fluorouracil, and high-dose leucovorin for locally advanced head and neck cancer: a clinical and pharmacologic analysis. 168 26

Methionine synthase, the enzyme that catalyses the transfer of a methyl group from 5-methyl tetrahydrofolate to homocysteine via the cofactor methylcobalamin, is one of the two established mammalian enzymes that utilise a biologically active vitamin B-12 derivative. Through its substrates, products and downstream metabolites, methionine synthase is directly involved in the sulphur amino acid pathways, polyamine biosynthesis, biological methylations and one-carbon-unit transfers. Rat liver methionine synthase was shown to be inactivated by the nitric oxide donor sodium nitroprusside. The inactivation occurred during the treatment of isolated rat hepatocytes in a time-dependent and dose-dependent manner with an apparent IC50 value of 170 microM. Highly purified rat liver methionine synthase was inactivated in a partially irreversible manner with an apparent IC50 value of 10 microM. The inactivation has been attributed to nitric oxide released by sodium nitroprusside. Since biomolecules possessing transition state metals are targets for nitric oxide, the possibility of a nitric oxide-cobalamin interaction could explain the observed inactivation. Nitric oxide is directly involved in different aspects of liver metabolic functions both under physiological and pathological conditions like sepsis and inflammation. The nitric-oxide-induced inactivation of methionine synthase could offer a rational explanation for the cellular and cytotoxic effects of this highly reactive molecule.
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PMID:The inactivation of methionine synthase in isolated rat hepatocytes by sodium nitroprusside. 910 60