Biomedical subjects

A Sekine

Publications and source records attributed to A Sekine.

44 records · Page 3Linked to original sources

PubMed1991

Angiocentric immunoproliferative lesion of the stomach.

We report here a rare case of angiocentric immunoproliferative lesion (AIL) of the stomach. The patient was a 61-year-old Japanese female whose medical history was unremarkable. Following a complaint of abdominal discomfort, a submucosal tumour of the stomach was found and gastrectomy was done. Histological examination of the tumour revealed multiple angiocentric or angiodestructive lesions with numerous lymphocytic infiltrates. These vascular lesions were histologically the same as those in benign lymphocytic vasculitis with granulomatosis (BLV) of the respiratory tract. AIL is a distinct entity, including BLV, lymphomatoid granulomatosis and angiocentric lymphoma with BLV representing a good prognosis group of AIL. A survey of the literature suggests that AIL is a spectrum of T-lymphocyte proliferative disorders. To our knowledge, this is the first case of AIL involving the stomach primarily.

Female↗

PubMed1990

Effects of FRG-8701 on gastric acid secretion, gastric mucosal lesions by necrotizing agents and experimental gastric or duodenal ulcer in rats.

Effects of FRG-8701, a new histamine H2-receptor antagonist, on gastric acid secretion, necrotizing agents-induced gastric lesions and acute gastric or duodenal ulcer in rats were studied. In lumen-perfused rats, intravenous injection of FRG-8701 reduced gastric acid secretion, and its antisecretory effect was almost equipotent to that of famotidine but the duration of action was substantially longer. In pylorus-ligated rats, the antisecretory effect of intraduodenal FRG-8701 administration was about 7 times more potent than that of cimetidine. FRG-8701 effectively inhibited macroscopic gastric hemorrhagic lesions induced by various kinds of necrotizing agents. Intraperitoneal injection was effective in preventing the lesions as well as oral treatment. The oral ED50 values for these lesions ranged from 1.1 to 9.4 mg/kg. On the other hand, famotidine failed to reduce these lesions, and the cytoprotective effect of cimetidine was observed only in high doses compared with the doses for antisecretory activity. In addition, the cytoprotective effect of FRG-8701 was not affected by the treatment of indomethacin or N-ethylmaleimide. FRG-8701 showed antiulcer activity against stress and indomethacin gastric ulcer and mepirizole duodenal ulcer. Its antiulcer effect was 5-15 times more potent than that of cimetidine. These results indicate that FRG-8701 is a new antiulcer drug that exerts a potent cytoprotective effect in addition to its gastric antisecretory activity.

Acetamides↗

PubMed1990

ADP-ribosylation of the rho/rac gene products by botulinum ADP-ribosyltransferase: identity of the enzyme and effects on protein and cell functions.

1. Botulinum C1 toxin and C3 exoenzyme were purified from the culture filtrate of type C Clostridium botulinum strain 003-9, and specific antibodies were raised against each protein. Immunochemical analysis using these antibodies revealed the presence of minute amount of a C3-like molecule in C1 toxin preparation which tightly binds to the toxin component(s). This enzyme complex was separated from the major neurotoxin. Thus, the ADP-ribosyltransferases in C1 and D toxins and C3 exoenzyme appear to come from the same origin, and should be called together botulinum C3 enzyme. 2. Botulinum C3 enzyme ADP-ribosylates the rho and rac gene products, a family of small molecular weight GTP-binding proteins homologous to ras p21s. This ADP-ribosylation occurs at Asn41 of the rho products which is located in their putative effector domain, suggesting that it interferes interaction of these GTP binding proteins with their effector molecules. 3. When incubated with PC-12 cells, the enzyme inhibits cell growth and induces neurites and acetylcholine esterase. Several lines of evidence suggest that the ADP-ribosylation of the rho/rac proteins is responsible for these changes.

ADP Ribose Transferases↗

PubMed1989

Asparagine residue in the rho gene product is the modification site for botulinum ADP-ribosyltransferase.

We reported previously that the ADP-ribosyltransferase in C1 and D botulinum toxins specifically catalyzes ADP-ribosylation of an Mr 22,000 guanine nucleotide-binding protein and that this substrate named Gb (b = botulinum) has an amino acid sequence homologous to that deduced from the rho gene (Narumiya, S., Sekine, A., and Fujiwara, M. (1988) J. Biol. Chem. 263, 17255-17257). In this study we have determined the amino acid sequence at its ADP-ribosylation site. Purified substrate was [32P]ADP-ribosylated by C1 botulinum toxin and digested with trypsin. The radioactive peptides were isolated by reversed-phase high performance liquid chromatography and digested further either with protease V8, with proteases V8 and thermolysin, or with proline endopeptidase and thermolysin. By this procedure three radioactive peptides were obtained, and their amino acid sequences were X-Tyr-Val-Ala-Asp-Ile-Glu, X-Tyr, and Val-Phe-Glu-X-Tyr in which no amino acid peak was found in X. During the sequencing the radioactivity quantitatively adhered to the sequencing filter and was not eluted with either of the identified amino acid residues. Analysis of the protein without the ADP-ribosylation yielded the corresponding sequence as Thr-Val-Phe-Glu-Asn-Tyr which corresponds to Thr37-Tyr42 in the amino acid sequence deduced from the Aplysia rho gene. These results strongly suggest that the asparagine residue is the ADP-ribosylation site in the rho gene product. This ADP-ribose protein bond was stable in 0.5 M hydroxylamine at pH 7.5 at 37 degrees C for at least 5 h. The ADP-ribosylation of this protein affected neither its GTPase- nor its [35S]guanosine 5'-O-thiotriphosphate-binding activity.

Adrenal Medulla↗

PubMed1988

Substrate for botulinum ADP-ribosyltransferase, Gb, has an amino acid sequence homologous to a putative rho gene product.

Gb (b for botulinum) is an Mr 21,000-22,000 guanine nucleotide binding protein which is specifically ADP-ribosylated by an ADP-ribosyltransferase produced by types C1 and D Clostridium botulinum (Morii, N., Sekine, A., Ohashi, Y., Nakao, K., Imura, H., Fujiwara, M., and Narumiya, S. (1988) J. Biol. Chem. 263, 12420-12426). In this study, we have identified the partial amino acid sequence of this protein. Purified Gb was digested with various proteases, and the proteolytic fragments were separated by high performance liquid chromatography. Isolated peptides were subjected to protein sequencing by an automated pulse-liquid phase protein sequenator. Eight partial amino acid sequences consisting of a total of 105 amino acid residues were obtained from 16 peptides. Computerized homology analysis revealed that they are homologous to the sequence deduced from cDNA of the rho genes. About 88% of the amino acid residues was identical between the sequenced Gb fragments and the corresponding regions of the Aplysia rho gene product. The result strongly suggests that Gb is a putative rho gene product.

Adrenal Glands↗

PubMed1988

Purification and properties of the cytosolic substrate for botulinum ADP-ribosyltransferase. Identification as an Mr 22,000 guanine nucleotide-binding protein.

The substrate for ADP-ribosyltransferase from Clostridium botulinum was purified from the cytosol of bovine adrenal gland. Purification procedures consisted of ammonium sulfate fractionation, chromatographies on columns of DEAE-Sepharose and phenyl-Sepharose, gel filtration on a TSK-gel G3000SW column, and Mono Q fast protein liquid chromatography. On DEAE-Sepharose chromatography, the substrate activity was eluted in two separate peaks, and electrophoretic analyses revealed that the substrates in the two peaks are of similar molecular weight but different isoelectric points. The major peak of the substrate was further purified. It was purified about 1,800-fold with a recovery of 2.2% by the above procedures. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the final preparation showed a single protein band at Mr 22,000. The purified protein served as a substrate for botulinum ADP-ribosyltransferase and was maximally ADP-ribosylated to the extent of about 0.7 mol of ADP-ribose/mol of protein. A guanosine 5'-(3-O-thio)triphosphate (GTP gamma S) binding activity was co-purified with the ADP-ribosylation substrate, and the purified protein maximally bound about 0.5 mol of GTP gamma S/mol. GTP gamma S binding was effectively competed by GTP and GDP but not by GMP, ATP, and ADP. Thus, the ADP-ribosylation substrate is a GTP-binding protein. This protein, designated Gb (b for botulinum), is widely distributed in various tissues. It was rich in brain, pituitary, and adrenal glands, and poor in heart, smooth, and skeletal muscles.

Adenosine Diphosphate Ribose↗

PubMed1985

Possible mechanisms of inhibitory action of sodium nitroprusside on histamine-induced contractile responses in isolated rabbit aorta compared with basilar artery and taenia coli.

Possible mechanisms of the inhibitory actions of sodium nitroprusside (NaNP) on histamine-induced contractile responses of isolated rabbit aorta, basilar artery and taenia coli were studied. NaNP (3 X 10(-5) M) reduced maximum contractile response to histamine in the aorta, whereas a concentration (10(-4) M) of NaNP slightly shifted the concentration-response curve for histamine towards its higher concentrations, but did not influence the maximum response in the basilar artery and taenia coli. The reduction in the maximum response of the aorta by NaNP was reversed by removal of the endothelium, or treatment with indomethacin (5 X 10(-6) M) or quinacrine (5 X 10(-6) M), but not by nordihydroguaiaretic acid (NDGA) (5 X 10(-5) M). Prostaglandin (PG) E1, PGE2 and PGI2 produced a relaxation in histamine-contracted basilar artery and taenia coli, whereas PGE1 and PGE2 produced a weak relaxation in histamine-contracted aorta. PGD2 relaxed taenia coli contracted by histamine, but had no influences in aorta and basilar artery. From these results, it is concluded that the inhibitory action of NaNP on histamine-induced contractile response in isolated rabbit aorta may be mediated at least partly by endothelium-derived arachidonic acid metabolite(s) via the cyclooxygenase pathway which must not involve PGI2. Furthermore, the difference in the inhibitory actions of NaNP between the tissues used in this study must be attributed to the absence of such mechanisms both in the basilar artery and taenia coli.

Animals↗

PubMed1983

The actions of sodium nitroprusside and diltiazem on calcium-, potassium- and histamine-induced contractile responses in isolated rabbit basilar artery, aorta, taenia coli and tracheal smooth muscle.

The effects of sodium nitroprusside (NaNP) and diltiazem on CaCl2-,KCl- and histamine-induced contractile responses were studied in isolated rabbit basilar artery, aorta, taenia coli and trachea. NaNP reduced CaCl2-induced maximal contractions in basilar artery and aorta, but little affected those in taenia coli and trachea. NaNP reduced histamine-induced maximal contraction markedly in aorta but slightly in basilar artery and taenia coli. The reduction in aorta was reversed by increasing CaCl2 contraction in bathing medium. NaNP inhibited histamine-induced contractions of basilar artery, aorta and taenia coli in Ca-free medium. Diltiazem reduced CaCl2-induced maximal contractions in basilar artery and aorta, whilst it caused a parallel shift of concentration-response curves for CaCl2 to the right in taenia coli and trachea. diltiazem reduced histamine-induced maximal contractions in basilar artery and taenia coli. These reductions were reversed by increasing CaCl2 concentration in bathing medium. Diltiazem strongly inhibited histamine-induced contraction of taenia coli in Ca-free medium. The effects of NaNP and diltiazem on KCl-induced contractions both in normal (Ca; 2.5 mM) and in high Ca (Ca; 12.5 mM) media were also studied. From the results obtained in this study, the actions of NaNP and diltiazem were considered to vary with the type of smooth muscle or the condition eliciting contraction. Their possible mechanisms were discussed in this paper.

Animals↗