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 type 1 glycogen storage diseases, glucose-6-phosphatase may be present but associated with impaired transport of glucose-6-phosphate (type 1b) or inorganic phosphate (type 1c) through microsomal membranes. The type 1c is very rare (2 published cases). The more frequent type 1b presents all the clinical manifestations of type 1a and specific signs: recurrent stomatitis, frequent infections, chronic inflammatory bowel disease secondary to neutropenia and neutrophil dysfunction. Glucose-6-phosphatase activity is low when measured on fresh liver tissue, but is restored after detergent treatment. A good metabolic control does not influence neutropenia and its consequences.
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PMID:[Glycogenoses type 1b and 1c]. 306 19

Polymorphonuclear leukocyte (PMN) function was investigated in two patients with glycogen storage disease type IB and neutropenia. Glycogen storage disease type IB was documented by liver biopsy and a normal amount of latent glucose-6-phosphatase activity. Patient A had stomatitis, skin infections, and septicemia; patient B had respiratory infections, periodontitis, and oral candidiasis. Absolute neutrophil counts ranged from 114 to 2580/mm3. Diminished and delayed migration of PMN into a skin "window" occurred in B. Random and directed PMN migration under agarose toward f-Met-Leu-Phe, pepstatin A, and zymosan-activated serum were severely diminished in both patients. At 10(-7) M f-Met-Leu-Phe, mean random and directed migration were 52 and 23% (A, n = 3) and 48 and 13% (B, n = 4) of controls. These results were independent of incubation time and chemoattractant concentration. Patients' PMN had diminished quantitative nitroblue tetrazolium reduction compared to controls. B had a significant defect in PMN bactericidal activity with Escherichia coli with less than 0.2 log killing at 2 h. These results further characterize the defect in PMN migration reported by Beaudet et al. (J Pediatr 97:906, 1980). The finding of other abnormalities of PMN function suggests a metabolic defect in the neutrophil which may be related to the microsomal membrane defect in hepatocytes in glycogen storage disease type IB.
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PMID:Impaired chemotaxis and neutrophil (polymorphonuclear leukocyte) function in glycogenosis type IB. 345 31

We have developed a cell-free system from Aedes albopictus (mosquito) cells which is able to carry out endogenous protein synthesis and is stable to freezing and thawing. Successful preparation of extracts was found to depend on the presence of purified placental RNase inhibitor during cell breakage. Micrococcal nuclease-treated extracts translated exogenously added Sindbis 26S or vesicular stomatitis virus mRNA with a high degree of fidelity, demonstrating that initiation of protein synthesis had occurred. Evidence is presented showing that when cell fractions containing intracellular membranes were used to translate vesicular stomatitis virus mRNA, the G protein was glycosylated and inserted into microsomal vesicles. Additional studies indicate that initiation of protein synthesis in this system is dependent on a capped and methylated 5'-terminal structure in the mRNA.
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PMID:Translation of vesicular stomatitis and Sindbis virus mRNAs in cell-free extracts of Aedes albopictus cells. 627 18

The fatty acids bound to the glycoproteins of Sindbis and vesicular stomatitis viruses can be released by treating the protein with 1 M hydroxylamine at pH 8.0, but the rates of release vary greatly among the three proteins. The most labile fatty acyl bonds were in the Sindbis virus PE2/E2 proteins and the most stable were in the E1 protein. Some of the fatty acids in Sindbis virus glycoproteins were reduced to the alcohol after treatment with sodium borohydride, indicating that protein-bound fatty acids could be in thiolester linkage. Sindbis virus PE2/E2 has several cysteine residues near the carboxy terminus, a region of the protein postulated to be localized on the inside (cytoplasmic face) of the bilayer, and protease digestion of microsomal membranes containing E2 protein removed a small portion of this cytoplasmic tail as well as significant amounts of the fatty acid. For the vesicular stomatitis virus G protein, the sensitivity of fatty acid hydrolysis appeared to depend on the conformation of the protein and a significant fraction of G protein was converted to a disulfide-linked dimer by hydroxylamine. These data implicate cysteinyl groups on these proteins as sites involved in fatty acid acylation.
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PMID:Release of fatty acids from virus glycoproteins by hydroxylamine. 632 73

We have carried out experiments designed to ask if it is possible to convert a secretory protein into an integral membrane protein by appending the membrane spanning domain of an integral membrane protein to its carboxy terminus. We first obtained expression of a cDNA clone encoding rat growth hormone (rGH) in eucaryotic cells, and found that this protein was secreted. We then constructed and expressed a hybrid gene encoding rGH fused to the membrane spanning and cytoplasmic domains of the vesicular stomatitis virus (VSV) glycoprotein (G). This fusion protein was anchored in microsomal membranes in the expected transmembrane configuration. The fusion protein was transported to the Golgi apparatus, and was esterified to palmitic acid, but it was not transported to the cell surface. We suggest that the sorting signal which allows rapid secretion of soluble rGH does not function when the protein is bound to the membrane.
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PMID:Conversion of a secretory protein into a transmembrane protein results in its transport to the Golgi complex but not to the cell surface. 658 49

The biosynthesis of the erythrocyte anion transport glycoprotein, Band III (Mr 100,000), is of interest, as its N-terminal half is hydrophilic and faces the cytoplasmic surface; the C-terminal half spans the phospholipid bilayer several times. Band III is synthesized by erythroid precursor cells obtained from the spleens of anaemic mice. Newly synthesized Band III was inserted into rough endoplasmic reticulum membranes with an asymmetric orientation which resembled that of mature Band III in erythrocyte membranes: the N-terminal portion of the molecule facing the cytoplasm. Newly made Band III contained a high-mannose asparagine-linked oligosaccharide, which was susceptible to cleavage by endoglycosidase H. During the next 20-30 min, this oligosaccharide was processed to a form resistant to endoglycosidase H degradation, presumably in the Golgi complex. The processed Band III was subsequently expressed on the cell surface, at about 30-45 min after synthesis. To study the mechanism of insertion of Band III into microsomes, we used erythroid precursor cells from the spleens of anaemic mice as a source of messenger RNA for studies in vitro in the wheat germ and reticulocyte lysate cell-free system containing dog pancreatic microsomes. Immediately after synthesis, Band III was found to be inserted into microsomal membranes in its mature configuration, with the N-terminal portion exposed to the cytoplasm and its hydrophobic C-terminal portion spanning the lipid bilayer. The newly-synthesized Band III was also provided with a high-mannose asparagine-linked oligosaccharide. Band III was found to be inserted into dog pancreatic microsomes in a co-translational manner; in synchronized translation studies microsomes could be added as late as the time when the hydrophilic N-terminal half of the protein had been synthesized and still allow normal trans-membrane insertion and glycosylation. There is no cleavage of any N-terminal peptide during membrane insertion. In many respects, therefore, the biosynthesis of Band III resembles that of co-translationally-inserted proteins whose N-terminal portions are exposed on the exterior of the cell, like vesicular stomatitis virus glycoprotein, HLA-A antigens, and glycophorin. However, our results suggest that Band III contains a sequence near the middle of the protein which directs its insertion into endoplasmic reticulum membranes.
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PMID:Synthesis and maturation of the erythrocyte anion transport protein--an internal sequence for membrane insertion. 682 84

Following p.o. administration to rats bearing advanced colorectal carcinoma, Ftorafur (FT) is converted to 5-fluorouracil (FUra) by microsomal P450 in the liver. To optimize the therapeutic selectivity of the FUra generated from FT, three approaches were utilized: (a) inhibition of FUra degradation to dihydrofluorouracil by uracil as an alternative substrate for uracil reductase in the molar ratio of 4 uracil:1 FT (UFT); (b) modulation of drug inhibition of thymidylate synthase by leucovorin (LV); and (c) by increasing the level of FUra incorporation into cellular RNA by N-(phosphonacetyl)-L-aspartate (PALA), an inhibitor of aspartate transcarbomylase. The maximum tolerated dose (MTD) of FT and UFT, administered 3 times a day for 28 days, was 150 mg/kg/day and 60 mg/kg/day, respectively. The MTDs were not significantly modified by LV (150 or 600 mg/kg/day), administered by the p.o. route with the drugs, or by PALA (100 mg/kg) administered weekly by the i.v. route. The dose-limiting toxicity of FT alone and in combination with the modulators was stomatitis. The severe alopecia observed with FT alone was reduced significantly by uracil. At the MTD, the antitumor activity of UFT was superior to those of FT and FUra alone and in combination with LV and/or PALA. The 3-month sustained complete tumor regression for UFT, FT, and FUra was 38%, 0%, and 13% (for the weekly schedule), respectively. Although uracil, LV, and PALA individually increased the antitumor activity of FT at its MTD, the combination of the three modulators produced the highest therapeutic efficacy in rats bearing advanced colorectal carcinoma, in which 100% of the treated animals achieved complete and sustained tumor regression. The therapeutic efficacy observed with FT modulation could not be achieved with FUra administered by different schedules, each at its MTD alone or in combination with either LV or PALA. In brief, modulation of FT produced greater therapeutic efficacy and selectivity than FUra. Furthermore, the combined use of modulators capable of inhibiting the degradation pathway of FUra and potentiating the effects of the anabolic metabolites action appears to offer the greatest therapeutic potential.
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PMID:5-Fluorouracil prodrug: role of anabolic and catabolic pathway modulation in therapy of colorectal cancer. 981 53

Mutations of the TSC2 gene lead to the development of hamartomas in tuberous sclerosis complex. Their pathology exhibits features indicative of defects in cell growth, proliferation, differentiation, and migration. We have previously shown that tuberin, the TSC2 protein, resides in multiple subcellular compartments and as such may serve multiple functions. To further characterize the microsomal pool of tuberin, we found that it cofractionated with caveolin-1 in a low-density, Triton X-100-resistant fraction (i.e., lipid rafts) and regulated its localization. In cells lacking tuberin, most of the endogenous caveolin-1 was displaced from the plasma membrane to a Brefeldin-A-sensitive, post-Golgi compartment distinct from the endosome and lysosome. Correspondingly, there was a paucity of caveolae at the plasma membrane of Tsc2-/- cells. Reintroduction of TSC2, but not a disease-causing mutant, reversed the caveolin-1 localization to the membrane. Exogenously expressed caveolin-1-GFP and vesicular stomatitis virus G protein, VSVG-GFP in the Tsc2-/- cells failed to be transported to the plasma membrane and were retained in distinct post-Golgi vesicles. Our data suggest a role of tuberin in regulating post-Golgi transport without apparent effects on protein sorting. The presence of mislocalized proteins in Tsc2-/- cells may contribute to the abnormal signaling and cellular phenotype of tuberous sclerosis.
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PMID:Tuberin is a component of lipid rafts and mediates caveolin-1 localization: role of TSC2 in post-Golgi transport. 1509 48

The C'-PNAb induced by JEV grown in porcine kidney stable (PS) cells [JEV(PS)] inactivate not only the corresponding virus, hut also Western equine encephalitis (WEE), Eastern equine encephalitis (EEE), vesicular stomatitis (VS) and Sindbis viruses grown in PS cells or primary hamster kidney (HK) cell cultures in the presence of complement. The degree of complement-potentiated neutralizing (C'-PN) ability varies for each virus. The C'-PNAb do not, inactivate these viruses grown in mouse brain, even JEV. The C'-PN activity against viruses other than JEV(PS) is completely removed by absorption with the microsomal fraction of PS or HK cells, but not of mouse brain. The antibodies in fraction IgM induced by the microsomal fraction of PS or HK cells inactivate the viruses grown in PS cells to a different degree in the presence of complement, but not viruses grown in mouse brain. The activity of C'-PNAb against JEV(PS) is reduced to 2% of the original activity by absorption with sheep red cells. After absorption, the remaining C'-PNAb are not further reduced by absorption with the microsomal fraction of PS cells, nor do they inactivate the other viruses grown on PS cells. The early rabbit hemagglutination-inhibition (HI) antibodies in fraction IgM induced by JEV(PS) could not only inhibit hemagglutination with JE, WEE, EEE, and Sindbis viruses grown on PS cells in the absence of complement, but could also facilitate HI in the presence of complement. However, they could not inhibit hemagglutination with these viruses grown in mouse brain, in the presence or absence of complement. This activity of HI could also be removed by absorption with the microsomal fraction of PS cells. These findings suggest that C'-PNAb are induced by host cell components associated with the virus, and that the early HI antibodies in fraction IgM are the same entities as C'-PNAb.
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PMID:Studies on complement-potentiated neutralizing antibodies (C'-PNAb) induced in rabbits inoculated with japanese encephalitis virus (JEV). I. The nature of C'-PNAb. 1861 6


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