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Biomedical subjects

K Tsuchida

Publications and source records attributed to K Tsuchida.

At least 109 records · Page 6Linked to original sources
PubMed1996

Effects of a new calcium antagonist, CD-832, on isoproterenol-induced myocardial ischemia in dogs with partial coronary stenosis.

Effects of CD-832 on isoproterenol (ISO)-induced myocardial ischemia were studied in dogs with partial coronary stenosis of the left circumflex coronary artery and findings were compared with those for nifedipine or diltiazem. In the presence of coronary artery stenosis, 3-min periods of intracoronary ISO infusion (10 ng/kg/min) increased heart rate and maximal rate of left ventricular pressure rise, which resulted in a decrease in percentage segmental shortening and ST-segment elevation of the epicardial electrocardiogram. After the control ISO infusion with stenosis was performed, equihypotensive doses of CD-832 (3 and 10 micrograms/kg/min, n = 7), nifedipine (1 and 3 micrograms/kg/min, n = 9) or diltiazem (10 and 30 micrograms/kg/min, n = 7) were infused 5 min before and during the second and third ISO infusion. Both CD-832 and diltiazem, but not nifedipine, significantly reduced the increase in heart rate induced by ISO infusion. In contrast to nifedipine, CD-832 (10 micrograms/kg/min) prevented the decrease in percentage segmental shortening from 32 +/- 12% to 115 +/- 26% of the control value (P < .01) and ST-segment elevation from 5.6 +/- 1.0 mV to 1.6 +/- 1.3 mV (P < .01) at 3 min after ISO infusion with stenosis. Diltiazem (30 micrograms/kg/min) also prevented the decrease in percentage segmental shortening from 34 +/- 14% to 63 +/- 18% of the control value (P < .05) and ST-segment elevation from 4.7 +/- 0.7 mV to 2.1 +/- 0.7 mV (P < .01) at 3 min after ISO infusion with stenosis. These data show that CD-832 improves myocardial ischemia during ISO infusion with stenosis and suggest that the negative chronotropic property of CD-832 plays a major role in the beneficial effects of CD-832.

Angina Pectoris↗
PubMed1995

Plasma homovanillic acid levels and therapeutic outcome in schizophrenics: comparisons of neuroleptic-naive first-episode patients and patients with disease exacerbation due to neuroleptic discontinuance.

Plasma homovanillic acid (pHVA) levels were measured and the Brief Psychiatric Rating Scale (BPRS) scores were evaluated in 26 schizophrenic patients who had either never been medicated (neuroleptic-naive, first-episode subjects) or whose condition had become exacerbated following neuroleptic discontinuance (exacerbated subjects). All the subjects received medication with a fixed dose of a neuroleptic (haloperidol or fluphenazine, both 9 mg/day) for the first week and variable doses for the subsequent 4 weeks. In the neuroleptic-naive subjects, pHVA levels increased significantly 1 week after starting the protocol; this increase correlated significantly with clinical improvement of the BPRS positive symptom scores at week 5. In the neuroleptic-naive subjects, pHVA levels had declined to the baseline level by week 5. In the exacerbated subjects, there were no significant correlations between pHVA level changes at week 1 and later improvements of the BPRS positive symptom scores. These results suggest that the rise in pHVA levels occurring within 1 week after starting a fixed neuroleptic dose may predict a favorable clinical response in neuroleptic-naive schizophrenic patients.

Adult↗
PubMed1995

The anti-emetic activity of GK-128 in Suncus murinus.

In Suncus murinus, various emetic responses and the anti-emetic activity of a new 5-hydroxytryptamine3 (5-HT3) receptor antagonist, GK-128 (2-[(2-methylimidazol-1-yl) methyl benzo[f]thiochromen-1-one monohydrochloride hemihydrate), were investigated. Cancer chemotherapeutic agents, cisplatin and cyclophosphamide, dose-dependently induced emesis of long-lasting duration. The 5-HT3 receptor agonist, 2-methyl-5-HT, and copper sulfate also induced emesis of short duration. However, another 5-HT3 receptor agonist, m-chlorophenylbiguanide, was not consistently emetic. GK-128 inhibited the emetic responses induced by chemotherapeutic agents and 2-methyl-5-HT with similar potency. The anti-emetic action of GK-128 was more potent than that of ondansetron, Y-25130, granisetron and metoclopramide. The order of potency of these drugs, except granisetron, was consistent with that of their 5-HT3 receptor binding affinity in rat cortex. GK-128 failed to inhibit copper sulfate-induced emesis. These data suggest that GK-128 has a potent inhibitory effect on emesis via the 5-HT3 receptor, and that the 5-HT3 receptor involved in emesis in Suncus murinus may be different from the classically defined 5-HT3 receptor in other animals such as rats, dogs and ferrets.

Animals↗
PubMed1995

N-acetylgalactosamine (GalNAc) transfer to the common carbohydrate-protein linkage region of sulfated glycosaminoglycans. Identification of UDP-GalNAc:chondro-oligosaccharide alpha-N-acetylgalactosaminyltransferase in fetal bovine serum.

During the course of a study of elucidate the role of modification of the common polysaccharide-protein linkage structure, GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl beta 1-O-Ser, in biosynthetic sorting mechanisms of the different sulfated glycosaminoglycan chains, a novel N-acetylgalactosamine (GalNAc) transferase was discovered in fetal bovine serum. The enzyme catalyzed the transfer of [3H]GalNAc from UDP-[3H]GalNAc to linkage tetrasaccharide and hexasaccharide serines synthesized chemically and to various regular oligosaccharides containing terminal D-glucuronic acid (GlcA), which were prepared from chondroitin and chondroitin sulfate using testicular hyaluronidase digestion. The labeled products obtained with the linkage tetra- and hexasaccharide serines and with the tetrasaccharide (GlcA beta 1-3GalNAc)2 were resistant to digestion with chondroitinase AC-II and beta-N-acetylhexosaminidase but sensitive to alpha-N-acetylgalactosaminidase digestion, indicating that the enzyme is an alpha-N-acetylgalactosaminyltransferase. This finding is in contrast to that of Rohrmann et al. (Rohrmann, K., Niemann, R., and Buddecke, E. (1985) Eur. J. Biochem., 148, 463-469), who reported that a corresponding product was susceptible to digestion with beta-N-acetylhexosaminidase. The presence of a sulfate group at C4 of the penultimate GalNAc or Gal units markedly inhibited the transfer of GalNAc to the terminal GlcA, while a sulfate group at C6 of the GalNAc had little effect on the transfer. Moreover, a slight but significant transfer of [3H]GalNAc was observed to an oligosaccharide containing terminal 2-O-sulfated GlcA as acceptor, whereas no incorporation was detected into oligosaccharides containing terminal unsaturated or 3-O-sulfated GlcA units. These results suggest that this novel serum enzyme is a UDP-GalNAc:chondro-oligosaccharide alpha 1-3- or 1-4-N-acetylgalactosaminyltransferase. The possibility of involvement of this enzyme in glycosaminoglycan biosynthesis is discussed.

Acetylgalactosamine↗
PubMed1995

Isolation of a novel collagen-binding protein from the mushroom, Hypsizigus marmoreus, which inhibits the Lewis lung carcinoma cell adhesion to type IV collagen.

A type IV collagen-binding protein of 23 kDa was isolated from the mushroom, Hypsizigus marmoreus. This protein, HM 23, bound to type IV and type I collagens and gelatin, and to much lesser extent to fibronectin, but not to laminin or bovine serum albumin. The adhesion of Lewis lung carcinoma cells was inhibited when the type IV collagen substratum was pretreated with HM 23. A computer search of the determined partial amino acid sequence indicated no homologous proteins reported. These results indicate that HM 23 is a hitherto undescribed fungus protein that can interact with animal extracellular matrix proteins.

Amino Acid Sequence↗
PubMed1995

Ontogeny of behavioral sensitization to cocaine.

The ontogeny of the behavioral effects of acute cocaine administration and behavioral sensitization to cocaine in rat pups was investigated. Acute behavior stimulating effects of cocaine were observed in pups as young as 7 postnatal days (PND) old, although they needed a higher dose of cocaine than adult rats to evoke the same motor effects. An adult dose-response curve pattern of stereotypy and locomotion to acute cocaine treatment was observed at PND 21, and of rearing at PND 28. Rats aged PND 7, 14, 21, 28, and 56 received repeated injections of saline or cocaine (15 mg/kg) twice a day for 5 consecutive days. After a 3-week period of abstinence, sensitization to a challenge dose of cocaine was assessed. Cocaine-induced stereotyped behavior was enhanced significantly only in rats in which cocaine pretreatment was initiated on PND 21, 28, and 56, but not earlier on PND 7 and 14. Adult female rats given repeated cocaine injections on PND 56-60 showed significantly greater sensitization than males, but no such sex difference was observed in pups given cocaine repeatedly on PND 21-25 or 28-32. These results show clearly that cocaine-induced behavioral sensitization in rats occurred only when subchronic cocaine administration was commenced on PND 21 or later.

Animals↗
PubMed1995

The sigma-selective ligand NE-100 attenuates the effect of phencyclidine in a rat diving model.

1. Phencyclidine (PCP) reduces the latency of rats diving into a water-filled pool from a hidden platform, without stereotyped behavior. 2. The sigma-selective ligand, NE-100 (N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethyl-amine monohydrochloride), attenuates the effects of PCP in this procedure. 3. The serotonin2 (5-HT2) antagonist, ritanserin, and the sigma receptor ligands, 1-(cyclopropylmethyl)-4-[2'(4"-fluorophenyl)-2'-oxoethyl]- piperidine HBr (Dup734), 4-[2'-(4"-cyanophenyl)-2'-oxoethyl]-1- (cyclopropylmethyl)piperidine (XJ448), alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol (BMY14802) and rimcazole similarly attenuate the effects of PCP. 4. The dopamine D2/sigma ligands, haloperidol and cis-N-(1-benzyl-2-methyl-pyrrolidin-3-yl)-2-methoxy-5-chloro-4- methylaminobenzamide (YM-09151-2) completely reverse the effects of PCP, whereas the same dose ranges of these drugs produce sedation. 5. The dopamine D2-selective antagonist, sulpiride, has no apparent effect on the PCP latency to the rat dive. 6. Thus, PCP-induced diving behavior was improved by sigma ligands and the 5-HT2 antagonist. This model of negative symptoms in an experimental animal will facilitate experiments on drug treatments for schizophrenia.

Animals↗
PubMed1995

Apolipophorin-III and adipokinetic hormone in lipid metabolism of larval Manduca sexta.

The hemolymph lipid levels were measured and the density of lipophorin was determined during late larval development in Manduca sexta. During the feeding phase of the 4th and 5th instar larvae the lipid level in hemolymph remained largely unchanged at less than 2 mg/ml. During the molt from 4th to 5th instar, the hemolymph lipid level increased, but decreased after feeding restarted in the 5th instar. In wandering larvae and prepupae the hemolymph lipid level increased from about 2 to nearly 10 mg/ml. The density of lipophorin from feeding larvae was found to be 1.148 g/ml with minor amounts of lipophorin having a lower density of about 1.128 g/ml and sometimes a small amount with a density of 1.174 g/ml. In molting larvae, however, the density was clearly lower, 1.116 g/ml. In wandering larvae of all ages, two predominant forms of lipophorin were observed; the density of these forms was 1.132 g/ml and 1.177 g/ml. Rarely, one or three different forms of lipophorin were observed. While the lipophorin of feeding larvae contains only apoLp-I and II (and lipids), the lipophorin of molting larvae contains in addition apoLp-III. ApoLp-III is seldom present in lipophorin from wandering larvae. According to our current models, lipophorin can take up only a certain amount of diacylglycerol before it needs apoLp-III for surface stabilization. Injection of 1 pmol of M. sexta AKH into feeding larvae increased the hemolymph lipid level, decreased the density of lipophorin to 1.125 g/ml and resulted in the association of apoLp-III with lipophorin. Cardiacectomy did not prevent feeding larvae from developing to wandering larvae.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Complete sternectomy for metastatic carcinoma with reconstruction using a latissimus dorsi musculocutaneous flap.

A 67-year-old man was hospitalized because of anterior chest pain and bulging. Histopathologic examination of a biopsy specimen revealed metastatic adenocarcinoma. For the metastatic sternal tumor a complete sternectomy was performed at all layers, following which the chest wall defect was reconstructed using no artificial materials but only a latissimus dorsi musculocutaneous flap. Postoperative respiratory function tests gave satisfactory results. This case suggests that, provided the organs within the thoracic cavity can be protected, solid or semi-solid stabilization achieved with artificial materials may not always be necessary, even in cases undergoing extensive sternectomy.

Adenocarcinoma↗
PubMed1995

Detection and characterization of UDP-GalNAc: chondroitin N-acetylgalactosaminyltransferase in bovine serum using a simple assay method.

We report the occurrence, in bovine serum of a soluble form, of N-acetylgalactosaminyl-transferase activity, which is involved in chondroitin sulfate biosynthesis, and we describe a simple assay method for the enzyme. Chondroitin with the general structure [GlcA-GalNAc], was found to serve as acceptor substrates for the enzyme. To develop a routine assay, bovine serum was incubated with polymeric chondroitin and UDP-[3H]GalNAc. After the removal of labeled endogenous acceptors derived from serum by trichloroacetic acid treatment, the labeled chondroitin sulfate chains were separated from residual unincorporated label by centrifugation using syringe columns packed with Sephadex G-25, and the effluent fractions were monitored by scintillation counting. This simple method allowed us to perform multiple assays and to establish assay conditions for the serum N-acetylgalactosaminyltransferase involved in chondroitin polymerization.

Animals↗
PubMed1995

Inactivation of activin-dependent transcription by kinase-deficient activin receptors.

Activin, a member of the transforming growth factor-beta superfamily, binds to two classes of cell surface receptors. These receptors, designated type I and type II, are structurally related members of transmembrane serine kinase superfamily. Antibodies specific for either type I or type II activin receptor can coprecipitate complexes containing both affinity-labeled receptors from activin-responsive cells. Two type I receptors show cell-specific expression and associate with the ligand-binding, type II receptors. To investigate the roles of the cytoplasmic receptor domains in signaling through a heteromeric ligand receptor complex, we have made kinase-deficient activin receptors and correlated their losses in kinase activity with inhibitory effects on an activin-dependent transcriptional response in activin-responsive cell lines. Wild-type activin type II receptors phosphorylate activin type I receptors in transfected COS cells. In contrast, kinase-deficient activin type II receptors fail to phosphorylate type I receptors in transfected COS cells and act as dominant negative mutants to block activin-induced transcriptional activity in both Chinese hamster ovary and K562 (human erythroleukemia) cells. Kinase-deficient activin type IB receptors also block activin-induced transcriptional activity in both Chinese hamster ovary and K562 cells, whereas kinase-deficient activin type I receptors have no effect in either cell line. These results indicate that kinase activities of both type II and type I receptors are required for activin signaling, and that the two type I receptors, which are expressed in a tissue-specific manner, are functionally distinct.

Activin Receptors↗
PubMed1995

A successful surgical treatment of coronary perforation associated with directional coronary atherectomy--a case report.

We encountered a patient with coronary perforation showing cardiac tamponade and shock that occurred during debulking by directional coronary atherectomy. We successfully performed emergent pericardial drainage and aorto-coronary bypass procedures. Bypass surgery is recommended to avoid perioperative myocardial infarction in cases such as ours since the native coronary artery may be at risk of being occluded or narrowed due to oppression by the hematoma and destroyed intima.

Aged↗
PubMed1995

[Mechanism of selection of NK-T cells in the thymus].

Thymic NK-T cells are defined as a novel T cell subset with characteristics of both T cells and NK cells, expressing TCR/CD3 complex and NK1.1. In the present study, we analyzed the mechanisms of selection of NK-T cells in the thymus by FACS and RNase protection assay. For the development of TCR alpha beta NK-T cells, class I but not class II MHC molecules are essential. However, as TCR alpha beta NK-T cell development is quite normal in TAP-1, a gene encoding peptide-transporter, deficient mice, TCR alpha beta NK-T cells may recognize vacant MHC class I molecule or MHC plus peptide presented by TAP-independent pathway. As NK-T cell express CD16 molecule, we examined whether CD16 molecule is essential for the development of NK-T cells. In FcR gamma chain mutant mice, the proportion of NK-T cells did not change as compared with normal mice, suggesting that CD16 molecule is not essential for the development of NK-T cells.

Animals↗
PubMed1994

Effects of CD-832, a dihydropyridine derivative with a nitrate ester moiety on rabbit femoral artery and vein.

We investigated the effects of CD-832 ((4R)-(-)-2-(nicotinoyl-amino)ethyl 3-nitroxypropyl 1,4-dihydro-2,6-dimethyl-4,3-nitrophenyl, 3,5-pyridine dicarboxylate), a dihydropyridine derivative with a nitrate ester moiety, on contractile responses in rabbit femoral arteries and veins. CD-832 (10(-8) to 10(-6) M and nifedipine inhibited the 64 mM KCl-induced and 10(-6) M norepinephrine-induced contractions of rabbit femoral arteries, while nitro compounds had no effect on the contractions. CD-832 (10(-8) to 10(-6) M) and nitro compounds inhibited the 10(-6) M norepinephrine-induced contractions in rabbit femoral veins, while other Ca2+ channel antagonists had little effect. The inhibitory effects of CD-832 (10(-7) M) on norepinephrine-induced contractions were antagonized by treatment with methylene blue (10(-5) M). These results indicate that CD-832 potently relaxes venous smooth muscle, and that it may be a useful agent for the treatment of angina pectoris.

Animals↗
PubMed1994

Monomeric activin A retains high receptor binding affinity but exhibits low biological activity.

Activins are multipotent hormones/growth factors that belong to the transforming growth factor-beta (TGF-beta) superfamily. Like TGF-beta s, activins have 9 conserved cysteine residues and are disulfide-bonded dimers. Based on the three-dimensional structure of TGF-beta 2, we deduced Cys80 in activin A to form the intermolecular disulfide bond. To obtain a monomeric form of activin, Cys80 was exchanged for a serine residue by polymerase chain reaction mutagenesis. The mutant protein was expressed in a baculovirus/insect cell expression system. The molecular mass of this mutant activin was determined to be 13 kDa (consistent with a single chain form of the protein) by SDS-polyacrylamide gel electrophoresis and by laser desorption mass spectroscopy. When this mutant monomeric activin was incubated with cells that expressed either the activin type IIB receptor or both the type I and type IIB receptors, its affinity was found to be 20% of that of native activin on a mass basis. Binding affinity determined using the mouse pituitary cell line AtT 20 was 10% of that of native activin A. Biological potency, however, as determined by the mutant protein's ability to release FSH from anterior pituitary cells in primary culture and by its ability to suppress basal ACTH secretion form AtT 20 cells, was only 1% of that of the native protein. This discrepancy of an order of magnitude between binding and biological activity is consistent with a model in which dimerization of the hormone is not necessary for high affinity binding to its receptor(s) while being essential for efficient signal transduction.

Activin Receptors↗
PubMed1994

A defective non-LTR retrotransposon is dispersed throughout the genome of the silkworm, Bombyx mori.

The presence of long repetitive sequences is demonstrated in the genome of the silkworm, Bombyx mori. Members of this BMC1 family reveal several features typical of the L1 (long interspersed sequence one) family of mammals, except for species specific elements. The number of BMC1 elements is estimated to be approximately 3500 per haploid genome. Elements containing the full length unit of 5.1 kb are dispersed throughout the genome and their restriction sites are conserved, although most members are preferentially truncated to varying extents at their 5' ends. DNA sequencing indicates that this element contains six tandem repeats of 15 bp CpG-rich sequence in the 5' proximal region. It terminates with a 3' oligo(A) stretch, and is flanked at both ends by a 7-10 bp target sequence duplication. In addition, there is significant evidence for amino acid sequence homology with reverse transcriptase domains of other L1 families, especially F, Doc and Jockey of Drosophila melanogaster. No large open reading frame is present. The BMC1 element is suggested to be dispersed in the genome by a transposition mechanism involving RNA intermediates.

Amino Acid Sequence↗