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)

In this clinical trial of men with advanced prostatic cancer no longer responsive to hormone therapy 189 were randomized to receive estramustine phosphate, methotrexate or cis-platinum. Response evaluations were done in 158 cases. Objective response rates (complete, partial or stabilization of disease) were 34 per cent for estramustine phosphate, 36 per cent for cis-platinum and 41 per cent for methotrexate. Subjective parameters indicated a substantial advantage for pain improvement with methotrexate or cis-platinum over estramustine phosphate. Probabilities of continued response indicated some advantage for methotrexate and median response durations at this time were twice as long for methotrexate (32 weeks) as for cis-platinum (16 weeks), with estramustine phosphate intermediate (23 weeks). Survival rates for the original treatment randomization groups were not different at this time. Side effects of estramustine phosphate consisted primarily of nausea and vomiting and/or anorexia but to a lesser extent than with cis-platinum. These effects were somewhat less for methotrexate, for which the major side effects were stomatitis and leukopenia, as well as hepatic toxicity reflected by elevated serum glutamic oxaloacetic transaminase levels. Other side effects of cis-platinum were less than for methotrexate (no stomatitis), except for signs of renal toxicity (elevations in blood urea nitrogen and serum creatinine), which were greater. Methotrexate had a relatively high level of activity against metastatic, progressive, hormone nonresponsive prostatic cancer, with side effects that were substantial but manageable.
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PMID:Comparison of estramustine phosphate, methotrexate and cis-platinum in patients with advanced, hormone refractory prostate cancer. 634 29

Rabies virus polysomes contained two sizes of messenger RNAs, one of which had a sedimentation value of 30S and another which sedimented at 12 to 16S. RNA extracted from infected cultures contained virion-size RNA, 42S, as well as 30S and 12 to 16S RNA species. Hybridization studies indicated that the 30S and 12 to 16S RNAs had nucleotide sequences which were complementary to virion RNA. RNA. RNA isolated from virus polysomes contained adenylate-rich sequences which were heterogeneous in size and were determined to be about 100 to 250 nucleotides in length on the basis of their migration rates in polyacrylamide gels. Acid-urea agarose gel electrophoresis established that the 30S RNA material was composed of a single RNA species (mol. wt. greater than or equal to 1.65 X 10(6)), whereas the 12 to 16S material could be resolved into at least four distinct species whose mol. wt. ranged from 0.28 to 0.87 X 10(6). When labelled rabies-infected cell RNAs, which were purified by oligo(dT)-cellulose chromatography, were annealed to excess unlabelled virus RNA, digested with ribonuclease T2 and the RNA duplex molecules analysed by polyacrylamide gel electrophoresis, five duplexes could be separated. The mol. wt. of these duplexes were estimated to be 3.2, 1.4, 0.96, 0.55 and 0.39 X 10(6), when compared to the known mol. wt. of vesicular stomatitis virus (VSV) RNA duplexes. This study suggests that the replicative processes of rabies virus are very similar to VSV and that rabies virus proteins are probably translated from smaller than virion-size RNAs.
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PMID:Rabies virus-induced RNA synthesis in BHK21 cells. 742 63

In a prospective study 27 patients (13 women, 14 men; mean age 62 [45-83] years) with Helicobacter (H.) pylori associated disease received over 7 days pantoprazole (40 mg twice daily), clarithromycin (500 mg twice daily) and metronidazole (500 mg twice daily). Six patients had gastric ulcer, 4 duodenal ulcer, 4 erosive gastritis, 6 erosive duodenitis and 7 had H. pylori-positive functional dyspepsia. Pre-treatment oesophago-gastro-duodenoscopy was combined in 4 patients with antral and in 4 others with body-of-stomach biopsies to demonstrate H, pylori (urease test, specific culture and histology). The H. pylori status was checked with the 13C-urea breath test 4 weeks after the end of treatment. In addition, 9 patients with peptic ulcer were examined endoscopically at least 2 weeks after onset of the treatment to check for any healing of the ulcers, 25 of the patients completed the study according to the protocol. The H. pylori eradication rate was 100% (25 of 25 patients), while the "intention to treat" analysis gave a rate of 92.6% (25 of the 27 patients). The peptic ulcers were found to be healed in all 9 patients who had been endoscoped. One woman developed a reversible stomatitis, but the drug treatment did not have to be stopped. -These findings indicate that short-term triple treatment in the described manner is efficacious in curing H. pylori infection and any peptic ulcer. It is thus a highly promising treatment of H. pylori-associated diseases.
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PMID:[Short-term triple therapy with pantoprazole, clarithromycin and metronidazole for the healing of Helicobacter pylori infection]. 788 16

Using three different trans dominant mutants of bovine ARF1 affecting GDP exchange or GTP hydrolysis we demonstrate the central role of ARF1 in controlling vesicular traffic from the endoplasmic reticulum (ER) to the Golgi apparatus and between successive Golgi compartments. Overexpression of ARF1(Q71L), a mutant likely to be restricted to the GTP-bound form, resulted in the accumulation of vesicular stomatitis virus glycoprotein in pre-Golgi intermediates, inhibited transport between successive Golgi compartments, and led to a striking association of beta-COP with pre-Golgi intermediates and the Golgi stack. In contrast, ARF1(T31N), a mutant which is likely to have a preferential affinity for GDP compared to the wild-type protein, inhibited export from the ER and triggered a brefeldin A-like phenotype, resulting in the redistribution of beta-COP from Golgi membranes to the cytosol and the collapse of the Golgi into the ER. This mutant, which may efficiently sequester an ARF-specific guanine nucleotide-exchange protein (ARF-GEF), suggests that ARF and ARF-GEF are essential for export from the ER. These results are discussed in the context of the GDP and GTP-bound forms of ARF in controlling both membrane structure and vesicular traffic through the early secretory pathway.
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PMID:Dominant inhibitory mutants of ARF1 block endoplasmic reticulum to Golgi transport and trigger disassembly of the Golgi apparatus. 828 10

Folding and refolding of the vesicular stomatitis virus (VSV) glycoprotein (G protein), New Jersey serotype, were studied both in infected cells and after urea denaturation and reduction of isolated protein in vitro. To assess the contribution of disulfide bonds to the conformation of this type I membrane glycoprotein, reduced and alkylated forms were compared with unreduced G proteins by their mobility on SDS-polyacrylamide gels and by their reactivity with conformation-dependent monoclonal antibodies (MAbs). Pulse-chase experiments showed that G protein folding in the endoplasmic reticulum (ER) of infected cells occurred rapidly (estimated half-time of 1-2 min) and involved transient association with the ER chaperone calnexin. Inhibition of glycosylation by tunicamycin slowed the folding process and emergence from the ER but did not prevent the appearance of a conformationally mature transport-competent G protein. For in vitro refolding studies, native G protein isolated from virus particles was denatured and reduced with urea and beta-mercaptoethanol. When rapidly diluted into a denaturant-free buffer containing oxidized glutathione and the nonionic detergent octyl glucoside, the G protein regained considerable native structure, as determined by reactivity with five monoclonal antibodies specific for different conformation-dependent epitopes. Whereas the refolding process was slow and inefficient in vitro relative to folding in the cell, this observation nonetheless demonstrated that an integral fully glycosylated membrane protein can be refolded to form a structure similar to that of the original protein processed during in vivo synthesis. If, however, unfolded nonglycosylated G protein was the starting material, refolding in vitro failed. In summary, we have shown that VSV G protein folding can be analyzed both in vivo and in vitro and that folding in the cell involves at least one chaperone and can occur in vivo even if not glycosylated.
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PMID:Folding, unfolding, and refolding of the vesicular stomatitis virus glycoprotein. 867 43

Microinjected GTP gamma S revealed three distinct steps in the exocytic transport of the temperature sensitive glycoprotein of vesicular stomatitis virus (ts-O45-G) from the ER to the cell surface in intact Vero cells. While COPII dependent export of ts-O45-G from the ER is blocked in cells injected with recombinant protein of a dominant mutant of SAR1a (SAR1a[H79G]) inhibited in GTP hydrolysis, neither injected GTP gamma S nor antibodies against beta-COP (anti-EAGE) interfere with this transport step significantly. In contrast, transport to the Golgi complex is blocked by 50 microM GTP gamma S, a dominant mutant of ARF1 (ARF1[Q71L]) inhibited in GTP hydrolysis, or microinjected anti-EAGE, but injected Sar1a[H79G]p has no effect. Microinjection of GTP gamma S or expression of ARF[Q71L] rapidly induces accumulation of COPI coated vesicular structures lacking ts-O45-G. Finally, transport of ts-O45-G from the trans-Golgi network (TGN) to the cell surface is inhibited only by high concentrations of GTP gamma S (500 microM). Interestingly, this step is only partially brefeldin A sensitive, and injected antibodies against beta-COP and p200/myosin II, a TGN membrane associated protein, have no effect. These data provide first strong in vivo evidence for at least three distinct steps in the exocytic pathway of mammalian cells regulated by different sets of GTPases and coat proteins. COPII, but not COPI, is required for ER export of ts-O45-G. COPI plays a role in subsequent transport to the Golgi complex, and a so far unidentified GTP gamma S sensitive coat appears to be involved in transport from the TGN to the cell surface.
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PMID:Three distinct steps in transport of vesicular stomatitis virus glycoprotein from the ER to the cell surface in vivo with differential sensitivities to GTP gamma S. 962 50

Fifty-nine children with Wilms' tumor (WT) were divided into a normal or poorly nourished group according to anthropometric parameters. The 2 groups were compared for morbidity and survival. There was no difference in the median age or stage of disease in the 38 well nourished and 21 poorly nourished children. There was no difference in the number of children in the normal or poorly nourished group who developed a raised urea or creatinine level, febrile episodes, severe stomatitis, varicella, or upper or lower respiratory infections, or who needed intravenous antibiotics, parenteral nutrition, or red cell and platelet transfusions. Projected survival rate was 56 and 74% for normal and poorly nourished children, respectively (p = .3). Poor nutrition at diagnosis, as determined by anthropometry, had no effect on the morbidity of treatment or survival in children with WT. Based on these results, selective dietary supplementation instead of routine intensive parenteral nutritional support for all children with WT is recommended in countries with limited resources.
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PMID:Nutrition, morbidity, and survival in South African children with Wilms' tumor. 1040 68

Bis-(8-anilinonaphthalene-1-sulfonate) (bis-ANS) causes inactivation of vesicular stomatitis virus (VSV) at micromolar concentrations while butyl-ANS and ANS are effective at concentrations one and two orders of magnitude higher, respectively. VSV fully inactivated by the combined effects of 10 microM bis-ANS and 2.5 kbar hydrostatic pressure elicited a high titer of neutralizing antibodies. Incubation of VSV with >/=2 M urea at atmospheric pressure caused very little virus inactivation, whereas at a pressure of 2.5 kbar, 1 M urea caused inactivation that exceeded by more than two orders of magnitude the sum of the inactivating effects produced by urea and pressure separately. Measurements of bis-ANS fluorescence showed that increasing the urea concentration reduces the pressure required to disrupt the structure. We conclude that anilinonaphthalene sulfonate compounds inactivate VSV by a mechanism similar to that produced by pressure. The most effective antiviral compound was bis-ANS which can be used for the preparation of safe viral vaccines or as an antiviral drug eventually.
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PMID:Virus inactivation by anilinonaphthalene sulfonate compounds and comparison with other ligands. 1097 27

While a sensation of thirst causes severe distress for a certain proportion of cancer patients in the terminal stage, the factors contributing to this symptom have not been established. To clarify the association between sensation of thirst and medical factors, especially dehydration, a cross-sectional observational study was performed on terminally ill cancer patients receiving inpatient hospice care. On admission to a palliative care unit, 88 consecutive patients underwent blood sampling and were requested to rate the intensity of thirst on a visual analogue scale (VAS). Physicians prospectively evaluated factors that might potentially be contributing to the symptom. The mean VAS score for thirst was 5.0+/-2.8, and 18% of the patients complained of severe thirst with a VAS score of > or = 8. No significant correlations were observed between the VAS score for thirst and the values of total protein, blood urea nitrogen (BUN), creatinine, sodium, osmolality, hematocrit, atrial natriuretic peptide (ANP), and biochemical dehydration defined by the levels of BUN, creatinine, sodium and osmolality. On the other hand, dehydration defined by ANP level (< or = 15 pg/ml), hyperosmolality (> or = 300 mosmol/kg), gastrointestinal cancer, survival, performance status, oral intake, vomiting, and stomatitis were significantly associated with the severity of thirst. In addition, mouth breathing and opioids were determined to be a potential clinical cause of severe thirst when a retrospective chart review was carried out. In conclusion, sensation of thirst is a frequent symptom in terminally ill cancer patients and is associated with dehydration, hyperosmolality, poor general conditions, stomatitis, oral breathing, and opioids. Careful assessments and treatment of underlying causes is important to alleviate patients' distress.
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PMID:Determinants of the sensation of thirst in terminally ill cancer patients. 1140 Oct 96

Arl1 is a member of the ARF-like protein (Arl) subfamily of small GTPases. Nothing is known about the function of Arl1 except for the fact that it is essential for normal development in Drosophila and that it is associated with the Golgi apparatus. In this study, we first demonstrate that Arl1 is enriched at the trans side of the Golgi, marked by AP-1. Association of Arl1 with the Golgi is saturable in intact cells and depends on N-terminal myristoylation. Over-expression of Arl1(T31N), which is expected to be restricted to the GDP-bound form and thus function as a dominant-negative mutant, causes the disappearance of the Golgi apparatus (marked by Golgi SNARE GS28), suggesting that Arl1 is necessary for maintaining normal Golgi structure. Overexpression of Arl1(Q71L), a mutant restricted primarily to the activated GTP-bound form, causes an expansion of the Golgi apparatus with massive and stable Golgi association of COPI and AP-1 coats. Interestingly, Golgi ARFs also become stably associated with the expanded Golgi. Transport of the envelope protein of vesicular stomatitis virus (VSV-G) along the secretory pathway is arrested at the expanded Golgi upon expression of Arl1(Q71L). The structure of stacked cisternae of the Golgi is disrupted in cells expressing Arl1(Q71L), resulting in the transformation of the Golgi into an extensive vesicule-tubule network. In addition, the GTP form of Arl1 interacts with arfaptin-2/POR1 but not GGA1, both of which interact with GTP-restricted ARF1, suggesting that Arl1 and ARF1 share some common effectors in regulating cellular events. On the basis of these observations, we propose that one of the mechanisms for the cell to regulate the structure and function of the Golgi apparatus is through the action of Arl1.
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PMID:Regulation of Golgi structure and function by ARF-like protein 1 (Arl1). 1179 19


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