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Biomedical subjects

Y Sugimoto

Publications and source records attributed to Y Sugimoto.

At least 271 records · Page 15Linked to original sources
PubMed1996

Genetic basis of left ventricular remodeling after myocardial infarction.

The purpose of the present study was to assess whether the insertion (I)/deletion (D) polymorphism of the angiotensin converting enzyme (ACE) gene, and the polymorphism of angiotensinogen (AGT) gene with threonine (T) instead of methionine (M) at amino acid 235 in exon 2 (M235T) were associated with left ventricular dilatation after myocardial infarction. In 103 patients with myocardial infarction, the left ventricular (LV) end-diastolic volume index (EDVI) and the end-systolic volume index (ESVI) were assessed by echocardiography at two time points, namely at 7 +/- 4 days and at 3.9 +/- 1.3 months (mean +/- S.D.) after the infarction. The increases in the LVEDVI and LVESVI on the second echocardiogram were significantly higher in subjects with the DD and ID genotypes than in patients with the II genotype (P < 0.05 and P < 0.005, respectively). Multiple regression analysis revealed that the LVESVI at the first echocardiographic examination and the ACE I/D genotype were significant predictors of the LVEDVI and LVESVI at the second echocardiographic examination. However, the AGT M235T genotype was eliminated. In conclusion, the DD and ID genotypes of the ACE gene were significantly associated with the progression of the LVEDVI and LVESVI after myocardial infarction. The presence of the deletion allele of the ACE gene may be a risk factor of congestive heart failure after a myocardial infarction.

Analysis of Variance↗
PubMed1996

Molecular aspects of the structures and functions of the prostaglandin E receptors.

Prostaglandin (PG) E2 exerts a variety of biological activities for the maintenance of local homeostasis in the body. The effects of PGE2 are exerted by a variety of PGE receptors which are different in their signal transduction properties and are classified into four subtypes, EP1, EP2, EP3 and EP4. We have isolated the mouse cDNAs for these PGE receptors and characterized the cloned receptors. EP1, EP2, EP3 and EP4 receptors consist of 405, 362, 365 and 513 amino acid residues with a putative seven hydrophobic domains, respectively. When expressed in mammalian cells, EP1 showed elevation of intracellular [Ca2+], EP2 and EP4 stimulated adenylate cyclase and EP3 inhibited the enzyme. Northern blot and in situ hybridization analyses have shown that these subtypes are differently localized to specific tissues and cells. We have identified multiple isoforms of the EP3 receptor (EP3 alpha, EP3 beta, and EP3 gamma) which differ in their carboxy-terminal domains. These isoforms displayed identical agonist binding properties, but were functionally different in the efficiency of G protein activation, the specificity of G protein coupling, and sensitivity to agonist-induced desensitization. The diverse physiological actions of PGE2 are elicited by the molecular diversity of the receptor subtypes and isoforms distributed differently in the body.

Amino Acid Sequence↗
PubMed1996

Primary culture of chicken hepatocytes in serum-free medium (pH 7.8) secreted albumin and transferrin for a long period in free gas exchange with atmosphere.

To study liver functions of chicken, we examined the primary culture of chicken hepatocytes, and found an easy method of long-term culture with free atmosphere exchange. Chicken hepatocytes were obtained by collagenase perfusion and cultured at 37 degrees C as a monolayer without substratum in serum-free L-15 medium (pH 7.8) with free atmosphere exchange. The amounts of albumin and transferrin in medium were assayed by ELISA. The culture of chicken hepatocytes was maintained in the serum-free L15-medium )pH 7.) and 37 degrees C with free atmosphere exchange for 20 days. The amount of albumin secreted in the medium decreased to low levels early in culture; however, this was followed by marked increase from day 9 to day 17 of culture. The amount of transferrin was constant until day 6, then it too increased with further culture. We reported an easy method for the simple monolayer culture of chicken hepatocytes in serum-free L12 medium (pH 7.8) with free atmosphere exchange over an extended period. Expression of liver-specific functions, viz. albumin and transferrin synthesis, was observed after 1 week of culture.

Air↗
PubMed1996

Keratinocyte growth factor (KGF/FGF-7) has a paracrine role in canine prostate: molecular cloning of mRNA encoding canine KGF.

cDNA encoding the canine keratinocyte growth factor (KGF) was cloned from normal canine prostate tissue. The authentic canine KGF cDNA sequence, 686 bp in length, spans the protein-coding region and 88 bp of the 5' and 19 bp of the 3' untranslated regions of canine KGF. The predicted amino acid sequence of canine KGF is composed of 194 amino acid residues. Canine KGF exhibits highest homology with the human KGF cDNA and amino acid sequences (95.8% and 97.4%, respectively), while it demonstrates the lowest homology with the rat sequences at 88.0% and 92.3%, respectively. The degrees of homology with mouse cDNA and amino acid sequences are 91.8% and 95.9%, respectively. By using RNase protection assay, KGF was shown to be expressed in normal prostate tissues of both mature and young (5-month-old) dogs. In vitro, the recombinant canine KGF has mitogenic activity on cultured canine epithelial cells, whereas it has no effect on cultured canine prostatic stromal cells. This novel canine KGF cDNA may be a valuable tool in the study of human benign prostatic hyperplasia using the canine prostatic as a model.

Amino Acid Sequence↗
PubMed1996

Characterization of 42 highly polymorphic bovine microsatellite markers.

We have isolated 42 highly polymorphic microsatellite (GT/CA)n markers from Japanese black cattle Wagyu (Bos taurus). Forty-one of the markers were assigned to bovine autosomes with lod scores > 6, through linkage analyses performed on the International Bovine Reference Family Panel (IBRP). The remaining marker showed X-linked inheritance. These markers exhibited an average heterozygosity value of 0.67 with between four and 17 alleles on the IBRP.

Alleles↗
PubMed1996

The effects of peripheral serotonin2 (5-HT2) and serotonin3 (5-HT3) receptor agonists on blood glucose levels in rats.

The involvement of the peripheral serotonin2A (5-HT2A) receptor in alpha-methyl-5-HT-induced hyperglycemia was examined in rats. The 5-HT2A receptor antagonist, ketanserin, significantly inhibited alpha-methyl-5-HT-elicited hyperglycemia. Taken together with a previous report that 5-HT-induced hyperglycemia was prevented by ketanserin, it is suggested that the peripheral 5-HT2A receptor participates in glucose regulation. As alpha-methyl-5-HT increased serum insulin but did not affect glucagon levels, it is indicated that these pancreatic hormones are probably not related to alpha-methyl-5-HT-induced hyperglycemia. Moreover, the peripheral 5-HT3 receptor agonist, 2-methyl-5-HT, did not affect blood glucose, insulin or glucagon levels. Our results therefore suggest that the peripheral 5-HT3 receptor is not involved in glucose regulation.

Animals↗
PubMed1996

Mechanism of Bradykinin-induced histamine release from rat peritoneal mast cells.

Bradykinin at concentrations higher than 2 microM caused a significant histamine release from rat peritoneal mast cells when extracellular Ca2+ was removed from the medium. Under the same experimental conditions, bradykinin increased Ca2+ release from the intracellular Ca store of the rat peritoneal mast cells, and a clear relationship was observed between the magnitude of histamine release and an increase in fluorescence intensity. Addition of Ca2+ to the medium resulted in an inhibition of the response to bradykinin in a concentration-dependent manner. Almost the same results were obtained when Mg2+, Ba2+ and La3+ were added to the medium. Neither B1 nor B2 antagonists caused significant antagonistic effects on histamine release induced by bradykinin. However, B2 antagonists caused a histamine release of the same potency as bradykinin when applied alone. These results indicate that bradykinin-induced histamine release is not attributable to a bradykinin receptor.

Animals↗
PubMed1996

Acid lipase inhibitor in chicken plasma identified as apolipoprotein A-I.

We have reported a inhibitor of acid lipases in liver lysosomes and erythrocytes from chickens [M. Fujii et al., Int. J. Biochem., 22, 895-898 (1990)]. In this paper, the properties of the inhibitor were described in comparison with those of apo A-I of chicken. The purified inhibitor migrated with the same mobility on SDS-PAGE as apo A-I, and had a molecular weight of 27,000. The peptide map from the lipase inhibitor was similar to that of apo A-I. Antibodies to the acid lipase inhibitor also reacted with apo A-I. Apo A-I inhibited the acid lipase activities of liver lysosomes and erythrocytes from chickens as strongly as the lipase inhibitor. The N-terminal amino acid sequence of lipase inhibitor was identical to that of apo A-I as far as residue 20. The amino acid sequence of peptides obtained from the inhibitor by cleavage with CNBr corresponded to internal sequence of apo A-I, and so the CNBr-peptides were derived by cleavage after the methionine residues in apo A-I. The findings showed that the inhibitor of the acid lipases in liver lysosomes and erythrocytes from chickens was identical to apo A-I.

Amino Acid Sequence↗
PubMed1996

Experimentally-induced prostatic hyperplasia in young beagles: a model to evaluate the chemotherapeutic effects of gossypol.

This study investigated the effect of gossypol on hyperplastic canine prostates induced with long-term administration of androgen and estrogen. Twelve 16-week-old male beagle dogs were divided evenly (n = 3) into 4 treatment groups: (1) CONTROL: vehicle only; (2) Gossypol-Treated: 20 mg/kg gossypol acetic acid; (3) Steroid-Induced: 4 mg/kg testosterone and 40 micrograms/kg estradiol-17 beta; (4) Gossypol-Treated and Steroid-Induced: 4 mg/kg testosterone, 40 micrograms/kg estradiol-17 beta and 20 mg/kg gossypol. The subjects received treatments every other day for 1 month. The beagles treated with steroids developed an acute enlargement (approximately 10-fold) of the prostate as compared to control. The prostatic acini were underdeveloped and characterized by simple squamous to low cuboidal epithelium in the control subjects while acini in steroid-induced subjects were characterized by simple tall columnar epithelium. The subjects treated with gossypol had prostates histologically similar to controls with the exception of loosened periurethral connective tissue. Serum testosterone and estradiol-17 beta levels imply that gossypol can reduce steroid hormonal levels. Mean serum testosterone levels in gossypol-treated subjects were reduced approximately 50% from controls. Serum biochemistry profiles indicate that steroid and/or gossypol treatments were not toxic at the doses and duration used in this study. These observations imply that gossypol and steroid hormones can interact to alter prostate development and gossypol metabolism and/or clearance.

5-alpha Reductase Inhibitors↗
PubMed1996

A novel pre-B acute lymphoblastic leukemia cell line with chromosomal translocation between p16(INK4A)/p15(INK4B) tumor suppressor and immunoglobulin heavy chain genes: TGFbeta/IL-7 inhibitory signaling mechanism.

p16 INK4A and/or p15 INK4B genes are frequently deleted in leukemias and other cancers. We have established a novel pre-B acute lymphoblastic leukemia (ALL) cell line (JKB2) with a chromosomal translocation between 9p2l and 14q32, on which p16INK4A/p15INK4B and heavy chain immunoglobulin (Ig) genes, respectively, are located. Homozygous deletions of P16INK4A/p15INK4B genes in JKB2 cells were confirmed by polymerase chain reaction, and their protein products were not detectable by Western blotting. Therefore JKB2 is the first example of an immunoglobulin heavy chain translocation associated with deletions of these genes. In JKB2 cells, cyclin-dependent kinase(CDK)4 and CDK6 formed complexes with cyclin D, due to the lack of p16, triggering phosphorylation of retinoblastoma protein (pRB) and continuous cell proliferation. Moreover, the growth of JKB2 cells was partially inhibited by TGF beta or IL-7, accompanied by decreased CDK4 and CDK6 expression, increased p2l and p27 expression, decreased p27 binding to CDK4/CDK6, and increased binding of p27 to CDK2. In addition, IL-7 both inhibited proliferation and induced differentiation of JKB2 cells. These studies suggest that a t(9;14)(p21;q32) chromosomal translocation can result in deletion of both p16 INK4A and p15 INK4B genes in pre-B ALL, and that the JKB2 cell line therefore provides a model for the study of leukemogenesis related to abnormalities in chromosome 9p2l. Moreover, they suggest that TGF-beta can, suppress JKB2 cell growth in a p15-independent mechanism.

Adolescent↗
PubMed1996

[Histological observation of anterior capsular edges produced by continuous curvilinear and diathermy capsulorhexis].

Radiofrequency endodiathermy capsulorhexis (DC) is a new method for anterior capsulorhexis in cataract surgery. DC may confer some advantages over continuous curvilinear capsulorhexis(CCC) in certain clinical situations. The elasticity of capsulorhexis produced by DC and the proper diathermy time are still unclear. Histological examination of rabbit lenses, on which a variety of coagulation times (0.5 to 5.0 sec) were tested revealed that 0.5 sec was long enough to coagulate the anterior capsule and that the longer coagulation extend the tissue damage into the deeper cortex. Small capsulorhexis (3.5 mm in diameter) produced experimentally with DC showed less elasticity than that produced with CCC when the edge of the capsulorhexis was pulled. Thus the heat coagulation of the capsular edge produced by DC results in less elasticity than that produced by CCC.

Animals↗
PubMed1996

Epileptogenic activity induced by combined treatment with antiinflammatory drugs and enoxacin and its inhibition by a calcium antagonist, nicardipine.

Epileptogenic activity induced by combined treatment with antiinflammatory drugs and enoxacin was investigated in chronic electrode-implanted rats. Ferubinac ethyl and aspirin DL-lysine showed a spike and wave complex in EEG without showing remarkable behavioral changes when they were injected intraventricularly, although a relatively high dose was needed. Enoxacin, on the other hand, elicited potent epileptogenic activity characterized by uninterrupted high voltage spike and wave complex at doses of 50 and 100 micrograms. At the same time, rats showed hyperactivity, jumping and violent convulsion. Combined treatment with enoxacin (p.o.) and ferubinac ethyl (i.v.) caused potent epileptogenic activity characterized by uninterrupted burst of high voltage spike and wave complex. Behaviorally, animals showed forelimb clonus, head nodding and generalized convulsion. High voltage spike and wave complex was also observed after combined treatment with enoxacin (i. vent.) and ferubinac ethyl (i.v. or i. vent.) in association with hyperactivity and jumping and violent convulsion. Nicardipine remarkably inhibited epileptic seizures induced by combined treatment with enoxacin (p.o.) and ferubinac ethyl (i.v.). It is concluded that simultaneous treatment with enoxacin and ferubinac ethyl produced epileptogenic activity when injected intraventricularly, and nicardipine inhibited convulsions induced by combined use of enoxacin (p.o.) and ferubinac ethyl (i.v.).

Animals↗
PubMed1996

Genesis of newt sperm axial fiber: cDNA cloning and expression of a 29 kDa protein, a major component of the axial fiber, during spermatogenesis.

Newt sperm has a unique structure: the tail consists of axial fiber, undulating membrane and flagellum. The genesis and chemical composition of the axial fiber remain unknown. The axial fiber consists of about 10 major components, as evidenced by SDS-polyacrylamide gel electrophoresis. In order to clarify the biochemical properties of the components of the axial fiber and study the mechanism of axial fiber formation, we focused our attention on a 29 kDa protein, the major constituent of the axial fiber. Immunofluorescent antibody technique showed that the 29 kDa protein was first expressed in the cytoplasm of early round spermatids but was expressed on fibers in the periphery of the cyst in late round spermatids. Double staining with tubulin antibody and 29 kDa antibody showed that the fibers around the cysts in early round spermatids were flagella alone but those in late round spermatids consisted of flagella and 29 kDa protein. These results indicated that 29 kDa proteins are synthesizsed in the cytoplasm of round spermatids and enter the preformed flagella in late round and elongated spermatids. A cDNA clone for 29 kDA protein was isolated. A database search could not find any homologous clones, indicating that the 29 kDa protein is a new one. Northern blot with the cDNA showed that mRNA for 29 kDa protein was highly expressed in round spermatids but barely in primary spermatocytes, indicating that the mRNA for 29 kDa protein is haploid-expressed.

Amino Acid Sequence↗
PubMed1995

Analysis of the in vitro translation product of a novel-type Drosophila melanogaster aldolase mRNA in which two carboxyl-terminal exons remain unspliced.

Drosophila melanogaster generates three different types of aldolase mRNAs from a single gene by selective usage of the triplicate exons 4 (4 alpha, 4 beta, and 4 gamma), which encode three different isozymes having respective carboxyl termini. We have found the presence of a novel-type mRNA (named alpha beta) in which two final exons, 4 alpha and 4 beta, were retained unspliced. Herein, a cDNA clone containing the alpha beta sequence was inserted into pINIII and expressed in an Escherichia coli system. The product, which exhibited aldolase activity, was found to be isozyme alpha from the primary structure and the enzymological properties, with the 4 alpha sequence alone being present as the carboxyl terminus. In tissues of D. melanogaster, the production of mRNA encoding exon 4 alpha is known to be restrained to a low level. This may be understood by the fact that the aldolase gene of this species does not have a typical poly(A) signal at the 3' end in exon 4 alpha. Instead, the transcript-encoding exons, 4 alpha and 4 beta, might be produced when AATATA, which resides downstream of the coding frame in exon 4 beta, is recognized as a poly(A) signal during RNA processing.

Alternative Splicing↗
PubMed1995

Molecular mechanisms of diverse actions of prostanoid receptors.

This review summarizes recent advances in the molecular characterization of prostanoid receptors. Prostanoids exert versatile actions in diverse tissues and cells through specific cell surface receptors. Molecular biological studies revealed the primary structure of eight types and subtypes of prostanoid receptor from various species. These include the thromboxane A2 receptor, prostacyclin receptor, prostaglandin (PG) F receptor, PGD receptor and four subtypes of PGE receptors. They are coupled to different signal transduction systems. In addition, multiple isoforms of PGE receptor EP3 subtype have been identified in various species. They are produced through alternative RNA splicing from a single gene and differ only in their carboxy-terminal tails. These isoforms differ in the efficiency of G protein activation, in the specificity of coupling to G proteins or in sensitivity to desensitization. This molecular characterization is useful for understanding the diverse physiological roles of prostanoids.

Amino Acid Sequence↗
PubMed1995

The mouse prostaglandin E receptor EP2 subtype: cloning, expression, and northern blot analysis.

A functional cDNA clone for the mouse prostaglandin (PG) E receptor EP2 subtype was isolated from a mouse cDNA library. The mouse EP2 receptor consists of 362 amino acid residues with seven putative transmembrane domains. [3H]PGE2 bound specifically to the membrane of Chinese hamster ovary cells stably expressing the cloned receptor. This binding was displaced by unlabeled prostanoids in the order of PGE2 = PGE1 >> iloprost, a stable PGI2 agonist > PGF2 alpha > PGD2. Binding was also inhibited by butaprost (an EP2 agonist) and to a lesser extent by M&B 28767 (an EP3 agonist), but not by sulprostone (an EP1 and EP3 agonist) or SC-19220 (an EP1 antagonist). PGE2 and butaprost increased the cAMP level in the Chinese hamster ovary cells in a concentration-dependent manner. Northern blot analysis revealed that EP2 mRNA is expressed most abundantly in the uterus, followed by the spleen, lung, thymus, ileum, liver, and stomach.

Amino Acid Sequence↗
PubMed1995

Selective coupling of prostaglandin E receptor EP3D to multiple G proteins depending on interaction of the carboxylic acid of agonist and arginine residue of seventh transmembrane domain.

Prostaglandin E receptor EP3D is coupled to stimulation and inhibition of adenylate cyclase and stimulation of phosphatidylinositol turnover. To examine the roles of the interaction of the carboxylic acid of an agonist and its putative binding site, the arginine residue in the seventh transmembrane domain of EP3D, in receptor-G protein coupling, we have mutated the arginine to the non-charged glutamine. TEI-3356, an EP3 agonist with a negatively charged the carboxylic acid, and TEI-4343, a non-charged methylester of TEI-3356, inhibited the forskolin-stimulated cAMP formation in the same concentration-dependent manner, but stimulation of basal cAMP formation and Ca2+ mobilization by TEI-4343 was much lower than that by TEI-3356. In the mutant receptor, both TEI-3356 and TEI-4343 showed the inhibition of forskolin-stimulated cAMP formation in the same profile, but did not stimulate basal cAMP formation or Ca2+ mobilization. These findings suggest that the interaction between the carboxylic acid of agonist and the arginine residue is important in signal transduction for adenylate cyclase stimulation and Ca2+ mobilization but not for adenylate cyclase inhibition.

Animals↗