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 used photocross-linking of peptides to DnaK to identify elements of the peptide binding site of DnaK. We attached a photoactivatable group (N-hydroxysuccinimidyl-4-azido-salicylic acid (NHS-ASA) or N-iodoacetamidobutyl-4-azido-salicylic acid (I-ABASA)) to different positions on peptide C of the vesicular stomatitis virus glycoprotein, 125I-radiolabeled the cross-linker, cross-linked the peptide to DnaK by UV irradiation, and then determined the amino acid residues of DnaK that were cross-linked to the peptide. Limited trypsin digestion of the DnaK-peptide complex revealed that the derivatives modified with photoactivatable cross-linker peptide C cross-linked to a C-terminal fragment of DnaK and that the N-terminal 45-kDa fragment of DnaK was not cross-linked by these modified peptides. The attachment points of the three peptide C derivatives carrying photoactivatable cross-linkers at different locations on the peptide, PepC-ASA, PepC-S7C-ABASA, and PepC-S8C-ABASA, have been identified as Arg-536, Arg-527, and His-541 of DnaK, respectively. Thus all three peptides cross-linked to amino acids located close together in a sequence that includes one end of the long alpha-helix in the NMR-based secondary structure model of the peptide binding domain of Hsp70 family (Morshauser, R., Wang, H., Flynn, G., and Zuiderweg, E. (1995) Biochemistry 34, 6261-6266).
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PMID:Identification of elements of the peptide binding site of DnaK by peptide cross-linking. 870 69

The phosphoprotein (P) of vesicular stomatitis virus was previously shown to assemble into a homomultimer upon phosphorylation by casein kinase II. It thus acquired transcriptional activity, including the ability to bind to the other two transcriptional components, the polymerase L and the N-RNA template. This multimer has now been found to be a trimer using a His-tag dilution method. Trimer stability was assessed using a variation of this method, by measuring the rate of exchange of monomers between preformed tagged and untagged trimers at different values of pH and ionic strength. Exchange rates increased with increasing ionic strength and were similar at pH 6, 8, and 10, but the trimer was completely dissociated at pH 4. This suggests that the trimer is stabilized by electrostatic interactions, probably involving carboxylate and guanidino groups. Addition of viral L protein stabilized the P trimers, completely preventing subunit exchange under transcription conditions. The association constants (Kass) for trimerization of partially active D and A substitution mutants were also determined by His-tag dilution and found to correlate well with transcriptional activity, further confirming that the active species is the trimer. Circular dichroism spectra were identical for phosphorylated and unphosphorylated wild-type P protein and for D and A mutants known to be predominantly trimeric and monomeric, respectively.
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PMID:The transcriptional form of the phosphoprotein of vesicular stomatitis virus is a trimer: structure and stability. 893 54

We have tested the impact of tags on the structure and function of indirect flight muscle (IFM)-specific Act88F actin by transforming mutant Drosophila melanogaster, which do not express endogenous actin in their IFMs, with tagged Act88F constructs. Epitope tagging is often the method of choice to monitor the fate of a protein when a specific antibody is not available. Studies addressing the functional significance of the closely related actin isoforms rely almost exclusively on tagged exogenous actin, because only few antibodies exist that can discriminate between isoforms. Thereby it is widely presumed that the tag does not significantly interfere with protein function. However, in most studies the tagged actin is expressed in a background of endogenous actin and, as a rule, represents only a minor fraction of the total actin. The Act88F gene encodes the only Drosophila actin isoform exclusively expressed in the highly ordered IFM. Null mutations in this gene do not affect viability, but phenotypic effects in transformants can be directly attributed to the transgene. Transgenic flies that express Act88F with either a 6x histidine tag or an 11-residue peptide derived from vesicular stomatitis virus G protein at the C terminus were flightless. Overall, the ultrastructure of the IFM resembled that of the Act88F null mutant, and only low amounts of C-terminally tagged actins were found. In contrast, expression of N-terminally tagged Act88F at amounts comparable with that of wild-type flies yielded fairly normal-looking myofibrils and partially reconstituted flight ability in the transformants. Our findings suggest that the N terminus of actin is less sensitive to modifications than the C terminus, because it can be tagged and still polymerize into functional thin filaments.
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PMID:Differential epitope tagging of actin in transformed Drosophila produces distinct effects on myofibril assembly and function of the indirect flight muscle. 988 Mar 32

An 84-year old man was admitted to Mitoyo General Hospital because of progressive malaise and edematous erythema on both eyelids (Heliotrope erythema). He also noted blister on his neck as well as erythema on the extensor surface of finger joints (Gottron's sign), elbows and knees. Neither weakness nor pain of his proximal muscle was elicited on physical examination on admission. His blood test disclosed positive inflammatory signs (i.e., mild elevation of ESR and positive CRP) without elevated value of muscle enzymes. Electromyogram showed normal pattern. Infiltration of inflammatory cells was not revealed by histological examination of biopsied muscle. A diagnosis of 'amyopathic dermatomyositis' was made based on these observations. Computed tomography of his chest disclosed interstitial pneumonia spreading over both lower lung fields. Colon fiberscopy revealed a polyp in his descending colon, which was classified into group I on cytological examination. He was treated with two sets of methylprednisolone (mPSL) pulse therapy (500 mg/day, 3 consecutive days, intravenously) followed by 30 mg/day of oral prednisolone (PSL). His skin lesions responded well to the above treatment and the dose of oral PSL was tapered. One month after the initiation of treatment, severe stomatitis as well as a large ulcer beneath his tongue developed accompanying an intractable pain. Mucosal biopsy revealed necrotizing vasculitis in medium-sizedartery at the bottom of ulcer. Another set of mPSL pulse therapy brought a prompt relief of his symptom and prohibited the recurrence of oral lesion. It should be noted that our patient did not fulfill the diagnostic criteria for DM because of the lack of muscular symptoms whereas he had characteristic skin lesions. Regarding the frustration possibly encountered at the time of diagnosing amyopathic DM, both sensitivity and specificity of the skin lesion for the diagnosis of DM were investigated. Moreover, the rarity of blister as a skin manifestation of DM was discussed as well.
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PMID:[A case of amyopathic dermatomyositis presenting blister and oral ulcer]. 1069 7

We present the case of a 72-year-old man with gastric tube cancer accompanied by multiple liver metastases, after esophagectomy for esophageal cancer, whose quality of life (QOL) was improved with a small dosage of TS-1. The patient's high serum AFP level suggested alpha-fetoprotein-producing gastric cancer. He was treated with half the standard dose of TS-1, because the patient's poor general condition necessitated chemotherapy with low toxicity and high efficacy. The daily dose was 40 mg for the first three courses and 50 mg for the last two. Each treatment course consisted of a four-week administration followed by two drug-free weeks. The patient received five courses of chemotherapy at our outpatient clinic before his death from re-progression of liver metastasis. No serious side effect except temporary stomatitis was observed. A decrease in tumor markers, alpha-fetoprotein and carcinoembryonic antigen, was obtained after 4 weeks. After 2 cycles, computed tomography and endoscopy examinations showed regression of the primary tumor and liver metastases, and tumor markers were decreased remarkably. The patient's QOL improved gradually after the treatment. His performance status before the chemotherapy was 3, and improved to 1 after two cycles. The small dosage of TS-1 was effective without any adverse effects, and improved the patient's QOL, for 6 months.
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PMID:[A patient with advanced gastric cancer in the gastric tube whose QOL was improved by TS-1]. 1191 37

Signalling lymphocyte activation molecule (SLAM, also known as CD150), a membrane glycoprotein involved in lymphocyte activation, has two extracellular immunoglobulin superfamily domains, V and C2. It has been shown previously that human SLAM is a cellular receptor for measles virus (MV) and that its V domain is necessary and sufficient for receptor function. Although mouse SLAM has functional and structural similarity to human SLAM, it hardly acts as a receptor for MV. By producing human/mouse chimeric molecules and assessing their receptor function with a vesicular stomatitis virus pseudotype assay, the region at amino acid positions 58-67 was found to be critically responsible for the difference in MV receptor function between human and mouse SLAMs. Exchange of this region allowed mouse SLAM to act as a receptor for MV, almost comparable to human SLAM. Among three amino acid differences (positions 60, 61 and 63) in this region, histidine 61 present in human SLAM was most significant, but combined substitutions with this residue and one or both of isoleucine 60 and valine 63 increased further the receptor activity of mouse SLAM. On the other hand, converse substitution at position 61 compromised receptor function of human SLAM. Thus, histidine 61 and its adjacent residues at positions 60 and 63 are critical for SLAM to act as a receptor for MV. Notably, the pseudotype assay indicated that residues at these three positions are also critical for the function of SLAM as a receptor for canine distemper virus.
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PMID:Histidine at position 61 and its adjacent amino acid residues are critical for the ability of SLAM (CD150) to act as a cellular receptor for measles virus. 1291 59

To further evaluate the clinical impact of recombinant PoIFN-alpha/gamma, PoIFN-alpha/gamma genes from a Chinese domestic big-white porcine breed were cloned using PCR, and expressed in a high-level prokaryotic system. The antiviral activities of rPoIFN-alpha/gamma on vesicular stomatitis virus (VSV), porcine reproductive and respiratory syndrome virus (PRRSV), and classical swine fever virus (CSFV) were investigated in different cell lines. The cloned PoIFN-alpha gene encodes a protein of 166 amino acids and has been named PoIFN-alphac. In a comparison of PoIFN-alphac with reported PoIFN-alphaI genes, eight amino acid substitutions at positions 43 (F to L), 78 (N to D), 86 (Y to C), 104 (A to V), 118 (R to L), 128 (T to P), 151 (S to V), and 156 (R to T) were observed, and resulted in no potential N-glycosylation site in the deduced PoIFN-alpha amino acid sequences. In contrast to PoIFN-alphac, one nucleotide substitution was found at position 462 (A to G), hence 0.1% synonymity is specific for the PoIFN-gamma gene. Both PoIFN-alphac and PoIFN-gamma genes were inserted into a prokaryotic vector pQE30, and expressed in E. coli M15 (pREP4) or SC11103 (pREP4) with the N-terminal six consecutive histidine residues, respectively. rPoIFN-alphac and rPoIFN-gamma proteins were detected by SDS-PAGE and Western blotting analysis at 20.7 and 18.0 kDa, respectively. In addition, the rPoIFN-alphac and rPoIFN-gamma protein were purified using Ni-NTA metal-affinity chromatography, and their anti-VSV, anti-PRRSV, and anti-CSFV activities were surveyed in homologous and heterologous cell lines. The results suggested that rPoIFN-alpha and rPoIFN-gamma could inhibit classical swine fever virus and other important viral pathogens in different cell lines.
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PMID:Cloning and expression of interferon-alpha/gamma from a domestic porcine breed and its effect on classical swine fever virus. 1566 33

Recent studies have demonstrated that covalent grafting of a single histidine residue into a twin-chain aliphatic hydrocarbon compound enhances its endosome-disrupting properties and thereby generates an excellent DNA transfection system. Significant increase in gene delivery efficiencies has thus been obtained by using endosome-disrupting multiple histidine functionalities in the molecular architecture of various cationic polymers. To take advantage of this unique feature, we have incorporated L-histidine (N,N-di-n-hexadecylamine) ethylamide (L(H)) in the membrane of hepatocyte-specific Sendai virosomes containing only the fusion protein (F-virosomes (Process for Producing a Targeted Gene (Sarkar, D. P., Ramani, K., Bora, R. S., Kumar, M., and Tyagi, S. K. (November 4, 1997) U. S. Patent 5,683,866))). Such L(H)-modified virosomal envelopes were four times more (p < 0.001) active in terms of fusion with its target cell membrane. On the other hand, the presence of L(H) in reconstituted influenza and vesicular stomatitis virus envelopes failed to enhance spike glycoprotein-induced membrane fusion with host cell membrane. Circular dichroism and limited proteolysis experiments with F-virosomes indicated that the presence of L(H) leads to conformational changes in the F protein. The molecular mechanism associated with the increased membrane fusion induced by L(H) has been addressed in the light of fusion-competent conformational change in F protein. Such enhancement of fusion resulted in a highly efficient gene delivery system specific for liver cells in culture and in whole animals.
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PMID:Histidylated lipid-modified Sendai viral envelopes mediate enhanced membrane fusion and potentiate targeted gene delivery. 1608 43

Membrane fusion is an essential step in the entry of enveloped viruses into their host cells triggered by conformational changes in viral glycoproteins. We have demonstrated previously that modification of vesicular stomatitis virus (VSV) with diethylpyrocarbonate (DEPC) abolished conformational changes on VSV glycoprotein and the fusion reaction catalyzed by the virus. In the present study, we evaluated whether treatment with DEPC was able to inactivate the virus. Infectivity and viral replication were abolished by viral treatment with 0.5mM DEPC. Mortality profile and inflammatory response in the central nervous system indicated that G protein modification with DEPC eliminates the ability of the virus to cause disease. In addition, DEPC treatment did not alter the conformational integrity of surface proteins of inactivated VSV as demonstrated by transmission electron microscopy and competitive ELISA. Taken together, our results suggest a potential use of histidine (His) modification to the development of a new process of viral inactivation based on fusion inhibition.
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PMID:Inactivation of vesicular stomatitis virus through inhibition of membrane fusion by chemical modification of the viral glycoprotein. 1693 41

The gene sequence encoding mature porcine interferon-gamma (PoIFN-gamma) fused with a C-terminal 6x histidine tag was cloned into the baculovirus pFastBac Dual vector of the Bac-to-Bac Baculovirus expression system under the control of PH promoter. The authentic signal sequence of porcine interferon-gamma was substituted with the honeybee melittin (HBM) signal sequence, and expressed in insect cells. The recombinant proteins were detected by SDS-PAGE and immunofluorescence assay. The nickel affinity column purified recombinant porcine interferon-gamma with HBM signal peptide (rPoIFN-gammaH) was shown to be a 19kDa protein as confirmed by Western blot analysis. The recombinant PoIFN-gammaH was shown to have cytokine activity, inhibiting the cytopathic effect of vesicular stomatitis virus (VSV) in PK-15 cells at about 1.07x10(6)U/mL. The 2(-7) dilution of the rPoIFN-gammaH in culture supernatant protected the MARC-145 cells from the cytopathic effect caused by 100TCID(50) of porcine reproductive and respiratory syndrome virus.
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PMID:Secretory expression of porcine interferon-gamma in baculovirus using HBM signal peptide and its inhibition activity on the replication of porcine reproductive and respiratory syndrome virus. 1955 14


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