Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have isolated and characterized the RNA of intracellular virus nucleocapsids recovered from a number of cell cultures persistently infected with rabies virus or vesicular stomatitis virus (VSV). VSV persistent infections in BHK21, L cells and Aedes albopictus (mosquito) cells generally showed the presence of large amounts of defective-interfering (DI) nucleocapsid RNA and much smaller amounts of standard (B) nucleocapsid RNA. Persistent infections of BHK21 cells by two rabies virus strains, challenge virus standard (CVS-11) or HEP-Flury, were followed for several months during which time the ratio of DI to B nucleocapsid RNA cycled dramatically. We also observed coordinated fluctuations in the absolute amount of incorporation of [3H]uridine into virus nucleocapsid RNA. Total incorporation was generally highest following a decrease in the relative amount of DI nucleocapsid RNA synthesis. At no time were DI nucleocapsids absent in any of the persistently infected cultures.
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PMID:Analysis of viral and defective-interfering nucleocapsids in acute and persistent infection by rhabdoviruses. 628 69

3-Deazauridine, a uridine analog, was administered to 36 patients with acute leukemia by both intermittent and continuous iv infusion at doses ranging from 400 to 6000 mg/m2/day x 5, repeated at 1--3-week intervals. There were no complete or partial responses but three patients showed hematologic improvement. Major toxic effects were myelosuppression, stomatitis, vomiting, diarrhea, and skin erythema. Daily doses greater than 3000 mg/m2 were associated with significantly increased toxicity, including three drug-related deaths. The recommended dose for future studies is 2500 mg/m2/day as a continuous 5-day infusion.
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PMID:Phase I--II study of 3-deazauridine in adults with acute leukemia. 723 73

Arildone (3 micro/ml) reduced the replication of murine cytomegalovirus, Semliki Forest virus, vesicular stomatitis virus, and coxsackievirus A9 by 64, 68, 94, and 98%, respectively. When the plaque reduction method was used to evaluate the antiviral effect for the viruses, a concentration of 3 to 5 micrograms/ml yielded a 50% reduction in plaque numbers. The effect of arildone on virus replication was greatest when the drug was present from the time of inoculation. The effectiveness decreased as the time interval from the inoculation of the virus to the addition of the drug increased. The removal of the drug from infected cells by washing readily reversed the effect, and viral replication resumed at a significant level. Infectivity of these viruses was not inactivated by the drug. Tissue culture cells used for viral growth and assay grew well in arildone (3 micrograms/ml), with cell yields that were comparable to those for cultures in the absence of drug. At 3 micrograms/ml there were minimal effects of the drug on the uptake of 3H-labeled amino acids and [3H]-thymidine into cells. Furthermore, incorporation of these precursors was not affected. However, there was a reduction in uptake of [3H]uridine into the acid-soluble pool and a concomitant reduction in incorporation into acid-insoluble counts.
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PMID:Antiviral activity of arildone on deoxyribonucleic acid and ribonucleic acid viruses. 744 5

Biochemical modulation can increase the efficacy of 5-fluorouracil (5-FU). Pizzorno et al. have previously shown that brequinar, a de novo pyrimidine synthesis inhibitor, enhances the antitumor effect of 5-FU in vivo [Cancer Res 52: 1660-1665, 1992]. On the basis of their data, we conducted a phase I study of brequinar in combination with 5-FU in patients with refractory solid tumors. The initial dose (100 mg/m2) of brequinar was raised in 100-mg/m2 increments in cohorts of three assessable patients. The initial dose of 5-FU was 500 mg/m2, but escalation was allowed in patients who showed no significant toxic reaction. Brequinar was administered over 1 h and 5-FU over 2 h starting 18-20 h after the initiation of infusion of brequinar. Treatments were repeated weekly. Responses were evaluated after 4 weeks (one course) and then every 8 weeks thereafter. Pharmacokinetics of brequinar and determination of plasma uridine levels were performed in at least three patients at each dose level. Of the 25 patients registered in the study, 21 were assessable for toxicity studies. The dose of brequinar was escalated up to 600 mg/m2. In addition, the dose of 5-FU was increased to 600 mg/m2 as a result of a lack of a significant toxic reaction in the first nine patients. No objective responses were observed. One patient developed grade 3 stomatitis, and one developed grade 3 esophagitis at the 400 and 600 mg/m2 dose of brequinar, respectively. Brequinar produced a dose-dependent decrease in plasma uridine levels at doses up to 500 mg/m2. No additional decrease in plasma uridine occurred with higher doses of brequinar, thus suggesting a plateau effect. This observation prompted us to terminate the study before reaching the maximum tolerated dose of brequinar. Our data indicate that brequinar in doses > or = 400 mg/m2 results in significant biochemical modulation. The lack of toxicity seen at these doses of brequinar suggests that the initial dose of the effector agent 5-FU should be increased in future studies.
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PMID:Biochemical modulation of 5-fluorouracil with brequinar: results of a phase I study. 763 78

The biochemical modulators PALA, an inhibitor of aspartate transcarbamylase which depletes uridine nucleotide pools, and 6-methylmercaptopurine riboside (MMPR) which inhibits purine metabolism, selectively potentiate the antitumor activity of 5-fluorouracil (5-FU) in preclinical models. Based on a phase I trial of this combination, we performed a phase II trial in patients with advanced pancreatic cancer. PALA 250 mg/m2 was administered i.v. on day 1, followed 24h later by MMPR 150 mg/m2 as a bolus i.v. injection, and 5-FU 2300 mg/m2 by 24h infusion. Treatments were repeated weekly. Seventeen patients, all previously untreated with chemotherapy, were entered, of whom 14 are evaluable for response. Toxicity > or = grade 2 included nausea (6/17), vomiting (4/17), diarrhea (3/17), stomatitis (5/17), and neurotoxicity (2/17). Among 14 evaluable patients there were no partial responses, and two patients with stable disease. Pretreatment with PALA and MMPR is insufficient to enhance the activity of 5-FU in pancreatic cancer.
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PMID:Phase II trial of PALA and 6-methylmercaptopurine riboside (MMPR) in combination with 5-fluorouracil in advanced pancreatic cancer. 777 33

Short-term effects of ethanol on human amnion cells were investigated by studying the cellular signaling processes and the replication of vesicular stomatitis virus. Treatment of human amniotic cells with ethanol transiently triggers the breakdown of inositol phospholipids, stimulates intracellular [Ca2+]i mobilization and activates the translocation of protein kinase C. Activation of this signal transduction mechanism is associated with the development of an antiviral state, as proven by studying 3H-uridine incorporation into the RNA of vesicular stomatitis virus. Induction of the antiviral state in human amniotic cells correlates with the solubility of the alcohols in the lipid membrane of the cells.
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PMID:Ethanol-induced signal transducing mechanism associated with a transient antiviral state in human amniotic cells. 793 58

Cytotoxic cells provide a crucial defense against DNA and RNA viral infections. Here we describe an in vitro model to study the fate of vesicular stomatitis virus (VSV) RNA in cells undergoing apoptosis. Using the [3H]uridine release assay, we show that human LAK cells induce the degradation of RNA in infected U937 cells in addition to inhibiting the production of infectious virions. LAK cell-mediated RNA degradation was blocked by the serine protease inhibitor, 3,4-dichloroisocoumarin. Purified human granzyme B but not inactivated granzyme B, granzyme A, or perforin rapidly induced degradation of RNA in VSV-infected U937 cells in a dose- and time-dependent manner without lysing the cells and suppressed viral production. Northern analysis of RNA extracted from infected cells with a VSV full-length cDNA probe confirmed that levels of viral transcripts were reduced by treatment with granzyme B. Nevertheless, the amount of host beta-actin mRNA was also reduced in infected cells, suggesting that treatment with granzyme B induced apoptosis. Consistent with this notion, infected cells exposed to granzyme B rapidly developed DNA strand breakage. Taken together, the data suggest that granzyme B in the absence of perforin reduced VSV production by activating a mechanism that degraded viral transcripts in infected U937 cells.
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PMID:Granzyme B independently of perforin mediates noncytolytic intracellular inactivation of vesicular stomatitis virus. 931 33

The matrix (M) protein of vesicular stomatitis virus (VSV) functions in virus assembly and inhibits host-directed gene expression independently of other viral components. Experiments in this study were carried out to determine the ability of M protein to inhibit transcription directed by each of the three host RNA polymerases (RNA polymerase I [RNAPI], RNAPII, and RNAPIII). The effects of wild-type (wt) VSV, v6 (a VSV mutant isolated from persistently infected cells), and tsO82 viruses on poly(A)+ and poly(A)- RNA synthesis were measured by incorporation of [3H]uridine. v6 and tsO82 viruses, which contain M-gene mutations, had a decreased ability to inhibit synthesis of both poly(A)+ and poly(A)- RNA. Nuclear runoff analysis showed that VSV inhibited transcription of 18S rRNA and alpha-tubulin genes, which was dependent on RNAPI and RNAPII, respectively, but infection with wt virus enhanced transcription of 5S rRNA by RNAPIII. The effect of M protein alone on transcription by RNAPI-, RNAPII-, and RNAPIII-dependent promoters was measured by cotransfection assays. M protein inhibited transcription from RNAPI- and RNAPII-dependent promoters in the absence of other viral gene products. RNAPIII-dependent transcription of the adenovirus VA promoters was also inhibited by M protein. However, as observed during wt VSV infection, M protein enhanced endogenous 5S rRNA transcription, indicating that the inhibition of transcription by RNAPIII was dependent on the nature of the promoter.
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PMID:Effect of vesicular stomatitis virus matrix protein on transcription directed by host RNA polymerases I, II, and III. 973 95

The search for antiviral agents against vesicular stomatitis virus, herpes simplex virus type 1 and poliovirus type 2 in plants extracts, led to the isolation of two antipoliovirus flavonoids from the medicinal plant Psiadia dentata (Cass.) DC, Asteraceae: 3-methylkaempferol and 3,4'-dimethylkaempferol. The antipoliovirus activity of both compounds was estimated by comparison with 3-methylquercetin, guanidine and Ro-090179. The most potent inhibitor of poliovirus replication was 3-methylkaempferol, and therefore we investigated its mechanism of action. We showed, using the inhibition of [3H]uridine incorporation in viral RNA and performing a dot-blot with one RNA probe specific for the poliovirus genomic strand RNA, that 3-methylkaempferol inhibits the genomic RNA synthesis of poliovirus.
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PMID:Antipoliovirus flavonoids from Psiadia dentata. 1190 Mar 47

From February, 2001 to September, 2002, the Southwest Oncology Group (SWOG) accrued 65 patients with advanced gastric adenocarcinoma to a phase II trial of weekly 5-FU, leucovorin, and the orally-administered uridine analog PN401. Of these 65 patients, 57 were assessable for survival and toxicity, which were the endpoints for the study. Treatment consisted of the administration of 1200 mg/m(2) of 5-FU, 500 mg/m(2) of leucovorin, and 6 grams of PN401 every 8 h, beginning 8 h after the completion of the 5-FU infusion, and continuing for a total of 8 doses (48 grams) during each weekly chemotherapy session. Therapy was delivered for six weeks out of every 8-week treatment cycle. The gastrointestinal toxicity of this regimen was mild with 2 patients experiencing grade 3 stomatitis, and 6 patients having grade 3 diarrhea; and the hematologic toxicity was acceptable with 6 of 57 patients found to have had grade 3 or 4 leukopenia, and 14 of 57 patients experiencing grade 3 or 4 neutropenia. There were two deaths judged possibly related to treatment; one in a patient who experienced a variety of Grade 2 gastrointestinal toxicities and died at home with an unknown cause of death; and a second patient who also died at home, and for whom treatment-related sepsis could not be ruled out. The overall median survival was 7.2 months. The ability to safely deliver twice the usual dose of 5-FU with leucovorin on a weekly schedule suggests that oral uridine analog supplementation with PN401 may enhance the therapeutic index of the fluoropyrimidines.
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PMID:Phase II trial of PN401, 5-FU, and leucovorin in unresectable or metastatic adenocarcinoma of the stomach: a Southwest Oncology Group study. 1683 2


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