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Biomedical subjects

K Goto

Publications and source records attributed to K Goto.

At least 739 records · Page 41Linked to original sources
PubMed1988

Cloning and sequence analysis of a cDNA for lymphocyte proliferation potentiating factor of rabbit polymorphonuclear leukocytes: identification rabbit interleukin 1 beta.

Complementary DNA for a rabbit PMN-derived lymphocyte proliferation potentiating factor (PMN factor) was cloned from a cDNA library constructed from poly(A)+RNA of early inflammatory exudate PMN. Oligodeoxyribonucleotides as probes for cloning were synthesized according to the previously reported amino acid sequence of the purified PMN factor. This cDNA encodes a 268-residue protein which is homologous to the established structures of human IL 1 beta (74%0 or murine IL 1 beta (71%). The NH2-terminal amino acid sequence of the endogenously produced PMN factor indicates that the mature molecule is made up of carboxy terminal 152 amino acids of the precursor molecule. Taking into consideration the previous studies on biological activities, this cloned PMN factor is therefore considered to be rabbit IL 1 beta.

Amino Acid Sequence↗
PubMed1988

Purification and partial sequence of rabbit polymorphonuclear leukocyte-derived lymphocyte proliferation potentiating factor resembling IL-1 beta.

A rabbit polymorphonuclear leukocytes (PMN)-derived lymphocyte proliferation-potentiating factor (PMN factor) was finally purified to homogeneity. PMN factor was released from early inflammatory peritoneal exudate cells (98% of PMN) stimulated with kaolin under roller bottle culture conditions. PMN factor was purified by large sequential scale steps, using membrane-type ion exchangers and gel filtration, followed in this order by HPLC steps with cationic ion exchangers and a hydroxylapatite column. Homogeneity was manifested based on the criteria of a single m.w. 18, 500 band on silver-stained polyacrylamide gel, a superimposable activity on a UV absorbance peak in analytic HPLC gel filtration, and detection of a single amino-terminal sequence. The homogeneous PMN factor had an isoelectric value of 7.2 and an activity of 1.9 x 10(7) U/mg in the thymocyte comitogenic assay. PMN factor stimulated one-half of the maximal response of thymocyte proliferation at 2.8 x 10(-12) M. Because of similarities in the physicochemical properties, specific activity, and amino-terminal sequence between rabbit PMN factor and human IL-1 beta, this PMN factor is therefore considered to be a rabbit IL-1 beta.

Amino Acid Sequence↗
PubMed1988

Positive chronotropic effects of endothelin, a novel endothelium-derived vasoconstrictor peptide.

Endothelin (ET) is a novel 21-amino-acid peptide isolated from the culture supernatant of porcine aortic endothelial cells, which has a potent vasoconstricting effect. It has been suggested that ET increases Ca2+ influx via a voltage-dependent Ca2+ channel. The purpose of the present study is to investigate the mode of actions of ET on the cardiac automaticity. ET increased the sinoatrial nodal rate in a dose-dependent manner on the isolated right atria of guinea pigs. The positive chronotropic effect of ET was very potent and the ED50 value was 0.4 nM. These results suggest that ET is one of the most potent cardio-acceleratory substances.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Exogenous delta-crystallin gene expression as probe for differentiation of teratocarcinoma stem cells.

We developed an experimental system in which differentiation of teratocarcinoma stem cell is probed by expression of stably introduced exogenous genes. We used chicken delta-crystallin gene (delta gene) and its derivative (Mo delta gene) driven by long terminal repeat (LTR) promoter of Moloney murine leukemia virus (Mo-MuLV). Neither of the genes was expressed in the undifferentiated condition. Differentiation to primitive endoderm induced by retinoic acid (RA) led to expression of delta but not Mo delta, while differentiation to more advanced endodermal cells by RA plus dibutyryl cAMP elicited Mo delta expression in addition to delta. These results are interpreted as a consequence of differential activation/suppression of gene expression through enhancer elements associated with the genes.

Alkaline Phosphatase↗
PubMed1988

Sensitivity and specificity of intracoronary injection of acetylcholine for the induction of coronary artery spasm.

Intracoronary injection of acetylcholine has been shown to induce coronary spasm in patients with variant angina. To examine its sensitivity and specificity, incremental doses of acetylcholine (20, 50 and 100 micrograms into the left coronary artery and 20 and 50 micrograms into the right coronary artery) were injected into the coronary artery or arteries in 70 patients with variant angina (Group 1) (mean age 57 years) and 93 patients without variant angina or angina at rest (Group 2) (mean age 54 years). Forty patients of the latter group had atypical chest pain, 16 cardiomyopathy, 14 arrhythmia, 11 valvular disease, 7 stable effort angina due to advanced coronary artery disease, 3 congenital heart disease and 2 hypertension. A temporary cardiac pacemaker set at 40 to 50 beats/min was positioned in the right ventricle. Coronary spasm was defined as total occlusion or severe vasoconstriction associated with chest pain or ischemic ST changes on the electrocardiogram or both. In Group 1, acetylcholine induced spasm in 63 (90%) of the 70 patients in the artery or arteries predicted to be responsible for spontaneous attacks. In Group 2, acetylcholine induced coronary spasm only in one patient with effort angina and advanced coronary artery disease although lesser degrees of vasoconstriction (less than or equal to 75% of the luminal diameter) occurred in most patients after acetylcholine (specificity of acetylcholine thus was 99%). In conclusion, intracoronary injection of acetylcholine is sensitive and reliable for the induction of coronary spasm.

Acetylcholine↗
PubMed1988

Suppression of exercise-induced angina by magnesium sulfate in patients with variant angina.

The effects of intravenous magnesium on exercise-induced angina were examined in 15 patients with variant angina and in 13 patients with stable effort angina and were compared with those of placebo. Symptom-limited bicycle exercise and thallium-201 myocardial scintigraphy were performed after intravenous administration of 0.27 mmol/kg body weight of magnesium sulfate and after placebo on different days. In all patients, serum magnesium levels after administration of magnesium sulfate were about twofold higher than levels after placebo. Exercise-induced angina associated with transient ST segment elevation occurred in 11 patients with variant angina receiving placebo and in only 2 of these patients receiving magnesium (p less than 0.005). On the other hand, exercise-induced angina was not suppressed by magnesium in any patient with stable effort angina. In these patients there was no significant difference in exercise duration after administration of placebo versus after administration of magnesium. The size of the perfusion defect as measured by thallium-201 scintigraphy was significantly less in patients with variant angina receiving magnesium than that in those receiving placebo (p less than 0.001), whereas it was not significantly different in patients with stable effort angina receiving placebo versus magnesium. In conclusion, exercise-induced angina is suppressed by intravenous magnesium in patients with variant angina but not in patients with stable effort angina. This beneficial effect of magnesium in patients with variant angina is most likely due to improvement of regional myocardial blood flow by suppression of coronary artery spasm.

Adult↗
PubMed1988

Developmental regulation of the chicken delta 1-crystallin gene: analysis by transgenesis and gene dissection.

We previously reviewed what we had learned about the regulation of the delta 1-crystallin gene through experiments using gene transfer techniques [Kondoh et al. (1986) Cell Differ. 19, 151-160]. It was concluded then that regulatory genetic elements for the lens-specific expression are associated with the delta 1-crystallin gene, and that these chicken elements properly function in mammalian cells. In the last couple of years, we have made significant progress in the understanding of lens-specific delta-crystallin expression. This is owing to success in transgenesis of mouse with the delta 1-crystallin gene and in functional dissection of the gene which led us to the discovery of an intragenic enhancer as the major determinant for lens-specific expression. In this article, we summarize these recent advances.

Animals↗
PubMed1988

Endocrine profiles and embryo quality in superovulated Japanese Black cattle.

The relationships between plasma concentrations of progesterone (P4), estradiol-17beta (E2) and lutenizing hormone (LH) and embryo yield and quality were examined in 40 superovulated Japanese Black cattle. The results indicated that the ovarian function, especially the function of corpus luteum on the first treatment day, is an important factor for reliable superovulation in cattle. The levels of plasma E2 and LH at estrus were related to embryo yield and quality.

Journal Article↗
PubMed1988

Primary structure, synthesis, and biological activity of rat endothelin, an endothelium-derived vasoconstrictor peptide.

Endothelin is a potent vasoconstrictor/pressor peptide, which we recently characterized from the conditioned culture medium of porcine aortic endothelial cells. We report here the cloning and partial sequencing of the rat endothelin gene. The nucleotide sequence predicted a 21-residue peptide similar to, but distinct from, porcine endothelin; 15 residues of rat endothelin were identical and 3 residues were substitutions by chemically similar amino acid residues to those in the porcine peptide. Synthetic rat endothelin was then prepared according to its deduced amino acid sequence. This synthetic peptide had (i) potent vasoconstrictor activity in the rat aortic strip and in perfused rat heart and (ii) a characteristically long-lasting in vivo pressor activity by intraaortic bolus injection in the conscious rat.

Amino Acid Sequence↗
PubMed1988

Cloning of the sequences expressed abundantly in established cell lines: identification of a cDNA clone highly homologous to S-100, a calcium binding protein.

To identify and characterize mRNAs which are abundant in established cell lines, but less so in the corresponding parental counterparts, a cDNA library was constructed from poly(A)+RNA of Balb/c3T3 cells. We screened this cDNA library by differential colony hybridization using single-stranded cDNAs from Balb/c3T3 cells and mouse embryo fibroblasts (MEF), and obtained four cDNA clones, out of 8,300 clones. One such clone, named pEL98, corresponding to mRNA of approximately 600 nucleotides, was further characterized. The entire nucleotide sequence of the cDNA insert in the pEL98 revealed a single open reading frame that encodes a 101 amino acid of putative protein (hereafter referred to as the pEL98 protein). pEL98 protein is highly homologous to both alpha and beta subunits of bovine S-100 protein (49 and 47% homology, respectively), a protein belonging to the family of calcium binding proteins. pEL98 protein is also homologous to several S-100 related proteins such as "calcyclin," a product of growth-regulated human gene 2A9, porcine p11 (or p10), the small subunit of a protein complex which serves as a major substrate of tyrosine kinase, and human cystic fibrosis antigen (CFAg). The amounts of transcript of pEL98 were increased in murine cells transformed with both activated oncogene and chemical carcinogen.

Amino Acid Sequence↗
PubMed1988

Acute phase response of plasma proteins in analbuminemic rats.

In healthy Nagase analbuminemic rats (NAR), the highest degree of relative increase in serum protein concentration was found for alpha-2-macroglobulin, the most prominent acute phase protein in rats. Its levels were about 30- and 60-fold higher in males and females, respectively, than those in the control Sprague-Dawley (SD) rats. In terms of absolute concentration, however, alpha-1-inhibitor 3 (also called alpha-X-protein or murinoglobulin) showed the most conspicuous change, its levels being higher by about 7 mg/ml than those in SD. When the acute phase reaction was induced by subcutaneous injection of turpentine, the levels of alpha-1- and alpha-2-macroglobulins, alpha-1-cysteine proteinase inhibitor, alpha-1-antiproteinase, and alpha-1-inhibitor 3 in NAR changed in essentially the same way as in SD: alpha-1-inhibitor 3 decreased markedly while the rest increased further. These results suggest that mechanisms responsible for the elevation of serum globulins in healthy NAR are not directly related to those involved in the acute phase response. On the other hand, the antithrombin III levels in healthy NAR were about twice the control values and changed little during the inflammation. In contrast, this protein in SD doubled during the acute phase, its maximal levels being close to those in healthy or inflamed NAR. This suggests that the antithrombin III level in healthy NAR is regulated by a mechanism similar to that in SD maximally reacting to the acute phase stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Proteins↗
PubMed1988

Experimental and clinical studies on epidermal growth factor for gastric mucosal protection and healing of gastric ulcers.

In experimental studies, 0.6 N HCl-induced gastric mucosal injury was significantly severe in submandibularectomized rats (SMR rats) than that in either SMR rats receiving exogenous mouse EGF (SMR + EGF rats) or controls. This was also true in gastric injury induced by 0.4 N HCl under pretreatment with indomethacin to reduce gastric mucosal prostaglandins (PGs). Somatostatin (SLI), PGE2, and PAS-stained mucus in the corpus were significantly reduced in SMR rats in comparison to SMR + EGF and control rats. In clinical studies, salivary EGF secretion was much higher in peptic ulcer patients than healthy controls. beta-Urogastrone was effective in the treatment of gastric ulcers. On the basis of experimental studies, we conclude that the protective effect of EGF on the gastric mucosa is, in part, mediated indirectly by increases in SLI, PGE2, and mucus production. However, endogenous, as well as exogenous, EGF has an important direct, cytoprotective effect on the gastric mucosa. From the clinical studies, we also conclude that salivary EGF secretion in ulcer patients increases in a homeostatic response to the presence of an ulcer, facilitating ulcer healing. Furthermore, we believe that beta-urogastrone, human EGF, might prove to be an effective drug in the clinical treatment of gastric ulcers.

Animals↗
PubMed1988

A novel peptide vasoconstrictor, endothelin, is produced by vascular endothelium and modulates smooth muscle Ca2+ channels.

Since the discovery of endothelium-dependent vasodilation, vascular endothelium has been recognized as an important functional unit contributing to the regulation of vascular tonus. Recent purification, structure determination and molecular cloning of a novel peptidergic vasoconstrictor, endothelin, from the culture supernatant of porcine aortic endothelial cells has further substantiated this concept. Starting from a large quantity of serum-fee endothelial cell-conditioned medium, endothelin was purified to homogeneity after three steps of high performance liquid chromatography by collecting active fractions and constricting porcine coronary artery strips. A peptide sequence analysis showed that endothelin was a previously unknown 21-residue peptide with two intrachain disulphide bonds. The EC50 of endothelin for contraction of porcine coronary artery was 4.0 x 10(-10) mol/l, indicating that endothelin is one of the most potent vasoconstrictors known. The pharmacological and structural properties of endothelin suggest that the peptide acts by activating voltage-dependent Ca2+ channels in vascular smooth muscle cells. Cloning and sequence analysis of complementary (c)DNA encoding porcine and human endothelin precursors showed that endothelin was produced de novo in endothelial cells from an approximately 200-residue prepropeptide through an unusual proteolytic processing by a putative 'endothelin-converting enzyme'. Northern blot analysis showed that preproendothelin messenger (m)RNA was expressed not only in cultured endothelial cells but also in fresh intimal tissue from porcine aorta, and that mRNA can be induced markedly in response to several vasoactive agents in cultured endothelial cells, suggesting the existence of a novel endothelium-mediated cardiovascular control system.

Animals↗
PubMed1988

Solubilization and characterization of calcitonin gene-related peptide binding site from porcine spinal cord.

The binding site for calcitonin gene-related peptide (CGRP) was solubilized with 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHAPS) in an active form from porcine spinal cord. 125I-labeled human alpha-CGRP (125I-CGRP) binding to the solubilized protein was determined by filtration using a GF/B glass filter. The maximal binding activity (approximately 60% of the crude membrane fraction) was obtained with 5 mM CHAPS. 125I-CGRP binding to the solubilized protein was of high affinity, saturability, and high specificity, having KD and Bmax values of 3.69 pM and 338 fmol/mg of protein, respectively. The binding activity was eluted in a single peak with a molecular mass of 400,000 daltons by gel filtration on TSK gel G4000SW. These results suggest that the solubilized protein may be responsible for the specific binding site.

Animals↗
PubMed1988

Permanent inflation of detachable balloons with a low-viscosity, hydrophilic polymerizing system.

A polymer system was developed for use in permanent inflation of detachable balloons, to avoid long-term reliance on the integrity of balloon shells or valve mechanisms. This system is based on 2-hydroxy-ethyl methacrylate (HEMA) as the monomer, in combination with a cross-linking agent and a water-soluble curing system. The low-viscosity, hydrophilic mixture can be exchanged through a small-bore catheter into a detachable balloon and polymerizes in 40-60 minutes at body temperature. Partially polymerized HEMA can cause vascular occlusion; hence, careful timing of balloon detachment is required. The evolution of the radiographic appearance of HEMA-filled balloons is predictable. The balloons remain radiopaque on plain radiographs as long as the balloon shell and valve mechanisms are competent. After rupture of the shell or failure of the valve mechanism, the balloons become invisible on plain radiographs but remain hyperattenuating on computed tomography scans.

Adult↗
PubMed1988

Positive inotropic action of novel vasoconstrictor peptide endothelin on guinea pig atria.

Endothelin (ET), a novel 21-amino acid peptide isolated from the culture supernatant of porcine aortic endothelial cells, has been shown to be the most potent of all known vasoconstrictor substances. The purpose of the present study was to investigate the effects and the mode of actions of ET on the heart. ET exerted a positive inotropic effect in a dose-dependent manner on the electrically driven left atria of guinea pigs. The ET-induced response was of slow onset and characteristically long lasting. The half-maximal effective dose of the ET-induced response was about 1 nM, indicating that ET is one of the most potent cardiotonic substances. The response was presumably caused through direct actions of ET on the myocytes, since adrenergic, histaminergic, and serotonergic antagonists showed no effect on the response. The dose-response relationship of ET for the positive inotropic effect was displaced to the right in a parallel fashion by 0.3 microM nicardipine. In the left atria depolarized with 22 mM KCl, ET produced gradually increasing contractions in conjunction with the slow response action potentials in response to the electrical pacing. These results suggest that the ET-induced response on the left atria is intimately related to the influx of extracellular Ca2+.

Action Potentials↗
PubMed1988

Positive inotropic effect of calcitonin gene-related peptide mediated by cyclic AMP in guinea pig heart.

The mechanism of cardiac actions of rat calcitonin gene-related peptide (CGRP) was analyzed on isolated guinea pig hearts. CGRP exerted a positive inotropic effect in a dose-dependent manner on the electrically driven left atria but not on the ventricles. Immunohistochemical studies demonstrated that CGRP-like immunoreactive nerves were distributed densely in the myocardia of the atria but only sparsely in those of the ventricles. The CGRP-induced augmentation of the contraction was accompanied by the shortening of the time to peak force and the increase in the relaxation velocity. The positive inotropic response to CGRP was significantly enhanced by isobutylmethylxanthine and was attenuated by adenosine. CGRP increased the action potential amplitude and prolonged action potential duration at the level of 50% repolarization in the left atria. In the preparations, which were partially depolarized with an increase in extracellular potassium, CGRP induced slow response action potentials. These electrophysiological results indicate that CGRP causes an increase in the slow inward Ca2+ current. The cyclic AMP content in the left atria significantly increased following the addition of CGRP, the time course of which was nearly consistent with that of the augmentation of the contractile force. In the membrane preparation of the atria, the activity of adenylate cyclase was enhanced by CGRP in a dose-dependent manner. These effects of CGRP are qualitatively similar to those of beta-adrenoceptor stimulation. It is concluded that the CGRP-induced response in the guinea pig atria is attributed to the activation of adenylate cyclase via stimulation of its specific receptor and the subsequent increase in the intracellular cyclic AMP level.

Action Potentials↗