Search PubMed⌕ Search

Biomedical subjects

H Hayashi

Publications and source records attributed to H Hayashi.

At least 919 records · Page 51Linked to original sources
PubMed1993

An additional arginine-vasotocin-related peptide, vasotocinyl-Gly-Lys, in Xenopus neurohypophysis.

The neurohypophysis of Xenopus and that of Ranidae and Bufonidae contain hydrin 1 (vasotocinyl-Gly-Lys-Arg) and hydrin 2 (vasotocinyl-Gly), respectively. In order to test the aldosterone-releasing activity of arginine vasotocin (AVT) and hydrin 1, purification of these peptides from an acid-extract of the neurointermediate lobe of Xenopus laevis was performed using an ODS-silica cartridge and reverse-phase and ion-exchange HPLC columns. As a result, an additional AVT-related peptide was newly found. Amino-acid analysis revealed that this peptide is vasotocinyl Gly-Lys (AVT-GK). The aldosterone-releasing activity of AVT-GK was equivalent to that of hydrin 1 (AVT-GKR) and lower than that of AVT. Like AVT and AVT-GKR, AVT-GK were effective in stimulating water flux from the isolated urinary bladder of the toad. Since AVT-GK is regarded as an intermediate between hydrin 1 and hydrin 2 in terms of its C-terminal form, it was designated hydrin 1'.

Aldosterone↗
PubMed1993

5-HT3 receptor antagonists. 2. 4-Hydroxy-3-quinolinecarboxylic acid derivatives.

A series of 4-hydroxy-3-quinolinecarboxylic acid derivatives (6) and 4-hydroxy-2-oxo-1,2-dihydro-3-quinolinecarboxylic acid derivatives (7) were designed and synthesized as 5-HT3 receptor antagonists. Molecular modeling studies suggested that the 3-carbonyl moiety in 6 was almost coplanar to the plane of an aromatic ring, but in 7 there was a 30 degrees deviation. 4-Hydroxy substitution in quinoline derivatives enhanced affinity for the 5-HT3 receptors, and endo-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-4-hydroxy-3- quinolinecarboxamide (6f) exhibited the most potent activity in the Bezold-Jarisch (B-J) reflex test (ED50 = 0.1 micrograms/kg, iv) among quinoline derivatives 6. Although 4-hydroxy-2-oxo-1,2-dihydro-3-quinolinecarboxamide derivatives (7a) exhibited higher affinity (e.g., 7d: Ki = 0.48 nM) for the 5-HT3 receptors than ondansetron (Ki = 7.6 nM) or granisetron (Ki = 2.1 nM), these amides showed less potent activity in the B-J reflex test than the reference compounds. Interestingly, the ester derivatives 7c, 7f, and 7h eliminated affinity for the 5-HT3 receptors. These unusual structure-activity relationships and the deviation of the 3-carbonyl moiety from the plane of an aromatic ring suggest that the active conformation of 7a might be different from the proposed one for the preceding 5-HT3 antagonists. Thus, 6f was chosen for further studies. No receptor binding for a variety of ligands was significantly antagonized by 6f. Comparing the ratios of the ED50 value in the B-J reflex test (rat, iv) with the LD50 value in acute lethal toxicity (mouse, iv), 6f was proved to have a 600-fold wider margin of safety than ondansetron. Compound 6f dose-dependently attenuated both the incidence and frequency of emetic episodes induced by cisplatin in the dog (ED50 = 14 micrograms/kg, iv) more potently than ondansetron (ED50 = 210 micrograms/kg, iv). Compound 6f (KF-20170) is now under further investigation as a drug for treating gastrointestinal disorder.

Animals↗
PubMed1993

Eclosion hormone activates phosphatidylinositol hydrolysis in silkworm abdominal ganglia during adult metamorphosis.

Eclosion hormone (EH), an insect neuropeotide, stimulated phosphatidylinositol (PtdIns) hydrolysis in abdominal ganglia isolated from Bombyx mori in a specific stage of adult development. Incubation of abdominal ganglia from silkworm pharate adults with EH led to an increase in formation of inositol 1,4,5-trisphosphate but this increase took place transiently, maximum increase being observed 30 s after the addition of EH. PtdIns hydrolysis was stimulated by exogenous EH in a dose-dependent fashion and was completely abolished by the phospholipase C inhibitors, neomycin and compound 48/80. The EH-induced PtdIns hydrolysis developed in parallel to the EH-induced eclosion behaviour during development of the adult. These results suggest that the EH-stimulated PtdIns hydrolysis plays an important role in EH-mediated signal transduction during adult development of B. mori.

Abdomen↗
PubMed1993

Rat liver aromatic L-amino acid decarboxylase: spectroscopic and kinetic analysis of the coenzyme and reaction intermediates.

The physiochemical properties of the coenzyme in rat liver aromatic L-amino acid decarboxylase (AADC) expressed in Escherichia coli have been studied by spectroscopic analysis of the enzyme, its reaction intermediates, and its complexes with substrate analogs. The enzyme, having one pyridoxal 5'-phosphate (PLP) per subunit, shows a prominent absorption maximum at 335 nm and a weaker one at 425 nm. The spectrum did not essentially change in the pH range of 6.0-8.0. When the coenzyme was excited at 335 nm, it emitted fluorescence primarily at 520 nm. The structure for the absorption at 335 nm was ascribed to the enolimine form of the PLP-lysine Schiff base. On the reaction of AADC with L-3,4-dihydroxyphenylalanine (L-dopa), the absorption of PLP showed biphasic changes before reaching a steady-state. Results of both pre-steady-state and steady-state kinetic analyses were consistent with the model that the reaction proceeds as shown in the equation: E + S<==>X1<==>X2-->E + P. The rate constant was determined for each step, and the Km value for L-dopa was obtained as 0.086 mM. The absorption spectra of the two intermediates, X1 and X2, were postulated from the calculation of the absorption changes during the first and the second steps of the reaction in which X1 and X2 showed an absorption maximum at 425 and 380 nm, respectively, with a concomitant decrease in absorbance at 335 nm. These predicted absorption spectra of X1 and X2 showed striking resemblances to those of AADC complexed with dihydroxyphenylacetic acid (DOPAc) and L-dopa methyl ester (DopaOMe), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Induction of apoptosis by hemorrhagic snake venom in vascular endothelial cells.

Vascular degeneration appears to play crucial roles in producing many vascular malfunctions (1-3). In order to identify specific inducers of programmed death in vascular endothelial cells (VEC), examinations were made of the effects of substances that are known to affect the vascular system by using VEC in culture (4,5). We found that hemorrhagic snake venoms induced apoptotic cell death or programmed cell death of VEC. By contrast, neurotoxic snake venoms did not induce programmed cell death but caused necrosis at much higher doses of the venoms. No effect of hemorrhagic venom was observed with many types of cultured cells other than VEC. Thus, hemorrhagic snake venom appears to be a useful tool for studies of the molecular mechanisms of vascular apoptosis. The results also suggest a possible mechanism of action of hemorrhagic snake venom on the vascular system.

Animals↗
PubMed1993

Effect of diabetes mellitus on hepatic resection.

We evaluated the effect of diabetes mellitus on mortality and morbidity after elective hepatic resections. Of 209 patients who underwent hepatic resections between April 1985 and July 1990, 49 (23.4%) were diabetic. Postoperative morbidity was more common among diabetics than among nondiabetics (75.5% vs 51.3%), mainly due to hepatic decompensation (55.1% vs 36.3%) and intraperitoneal sepsis (18.4% vs 6.3%). However, their incidence of hospital death (2% vs 2.5%), mean +/- SD postoperative hospital stay (36.1 +/- 20.2 days vs 29.4 +/- 28.2 days), and long-term survival were comparable with those of nondiabetics. Diabetics with and without complications were similar in preoperative or postoperative insulin requirement, duration of diabetes, and preoperative fasting glucose. Nevertheless, all eight patients with 24-hour urinary glucose excretion above 1 g developed complications. We conclude that diabetics are at a high risk of morbidity, but not of mortality after elective hepatic resection.

Adolescent↗
PubMed1993

Effects of intravenous SM-9527 (double-chain tissue plasminogen activator) on left ventricular function in the chronic stage of acute myocardial infarction.

Clinical effects of thrombolytic agent SM-9527 (double-chain tissue plasminogen activator) on left ventricular (LV) function were assessed in patients with acute myocardial infarction (AMI). A dose of 30 x 10(6) IU SM-9527 was given intravenously to patients with AMI within 6 h after onset. Of 159 candidates, 20 were excluded from the trial due to diseases other than myocardial infarction or failure to meet the protocol requirements; 114 of the remaining 139 were subjected to LV function analysis. The following results were obtained: (1) Patients with successful reperfusion in response to SM-9527 in the acute stage without later reocclusion revealed a significant improvement of LV function in the chronic stage. (2) Adverse effects were noted in 15 patients (10.8%), but none were serious; all were bleeding related to catheterization. (3) Hemagglutination fibrinolysis system test revealed no problems. It is concluded that early thrombolytic therapy with intravenous SM-9527 for AMI provides significant improvement of LV function in the chronic stage.

Adult↗
PubMed1993

Comparison between diurnal distribution of onset of infarction in patients with acute myocardial infarction and circadian variation of blood pressure in patients with coronary artery disease.

We analyzed the diurnal distribution of the onset of infarction in 636 patients with acute myocardial infarction (MI) and compared it with the circadian variation of blood pressure in 57 patients with coronary artery disease (CAD). In addition, we studied the modification of the circadian blood pressure variation during treatment with antianginal medications in 20 patients with CAD. A marked diurnal periodicity (p < 0.05) was observed for the onset of MI, with peaks seen in the late morning, late evening, and very early morning. The blood pressure in the patients with CAD was elevated in the morning, reduced in the late evening, and was the lowest in the very early morning. The peaks of onset of infarction temporally corresponded to the characteristic feature of blood pressure profile observed in the patients with CAD, that is, the morning rise, the late evening decline, and the very early morning reduction. Antianginal medications significantly reduced the blood pressure, not only during the day (p < 0.02) but also at night (p < 0.05). These observations suggest that the decline in blood pressure, as well as the morning surge in blood pressure, may be closely related to the onset of MI. Therefore, when treating patients with CAD with antianginal medications which can potentially reduce blood pressure, the effects on the circadian variation of blood pressure should be considered.

Blood Pressure↗
PubMed1993

Histomorphometry of immature rat testis after heating.

The scrotal testes of albino rats aged 35 and 45 days were immersed in water at constant temperatures of 43 degrees C, 44 degrees C, or 45 degrees C for periods of 15-45 min in a special heating device. At an age of 60 days, the rats were mated in individual cages with two primiparous rats each. At an age of 90 days, they were killed and their testes were histologically processed. Rats with testes that had been subjected to heating when the animals were 45 days old showed both alterations of the seminiferous tubules and a decrease in fertilizing capacity. The effect of heat was greater in animals at 45 than at 35 days of age. In heat-treated testes, tubules contained PAS-positive concretion, sometimes engulfed by macrophage-derived giant cells and multinucleate cells derived from spermatids that failed to separate during spermiogenesis. The decrease in testicular volume observed after heat treatment was due mainly to reduced parenchymal volume. Thermic lability of seminiferous stem cells increases with age until adulthood, and recovery from heat injury declines.

Age Factors↗
PubMed1993

Inhibitory effects of a cholecystokinin antagonist, loxiglumide (CR-1505), on the growth of freshly separated and xenografted human pancreatic cancer.

The effects of cholecystokinin (CCK) and a CCK antagonist, loxiglumide (CR-1505), on four freshly separated and six xenografted human pancreatic cancers, were investigated. The level of DNA synthesis in only one of five tested pancreatic cancers was enhanced by CCK at concentrations of 0.01-10 nM, while in the other four cancers DNA synthesis was not affected. The levels of DNA, RNA, and protein synthesis (by 3H-thymidine, 3H-uridine, and 3H-leucine incorporation tests, respectively) in all the tested cancers were dose-dependently inhibited by loxiglumide at concentrations of 20-2000 microM, and the IC50 of loxiglumide for DNA synthesis in pancreatic cancers was 156 +/- 80 microM (means +/- SD). The in vivo effect of loxiglumide was assessed using a xenografted line (PC-HN) transplanted in nude mice. The in vivo 50% lethal dose of loxiglumide for nude mice was about 500 mg/kg. Death was caused by respiratory failure due to severe congestion of the lung after the administration of a large dose of loxiglumide. The growth of a PC-HN transplanted in the nude mice was significantly inhibited by subcutaneous loxiglumide at 250 mg/kg, twice a day for 28 days, which did not cause death. It is suggested that loxiglumide inhibits the in vivo and in vitro growth of human pancreatic cancer, perhaps independently of its action as a CCK antagonist, and this study also suggests that loxiglumide may be a new type of therapeutic agent to be used for the treatment of human pancreatic cancer.

Animals↗
PubMed1993

Hepatotoxin (microcystin) and neurotoxin (anatoxin-a) contained in natural blooms and strains of cyanobacteria from Japanese freshwaters.

Amounts of hepatotoxic microcystin and neurotoxic anatoxin-a were estimated in natural blooms and strains of cyanobacteria from freshwaters in Japan. A simultaneous analysis method of anatoxin-a and microcystin was applied to natural bloom samples, which has been dominated by several species and the strains of cyanobacteria which produced simultaneously both toxins. The natural blooms examined in the present study were mainly composed of Anabaena and Oscillatoria, but most also contained Microcystis and other cyanobacteria. Only one sample was almost unialgal, Anabaena spiroides, collected from Lake Sagami. The toxins in 14 samples collected from nine different natural blooms during 1988-1992 were identified as microcystins-RR, -YR, and -LR; desmethyl-7-microcystin-LR (7-DMLR); and anatoxin-a. Microcystins were the main toxins contained in these natural blooms, with anatoxin-a not being detected or of very little quantity. 7-DMLR was detected in samples only from Lake Kasumigaura. Five strains of Anabaena isolated from waters in Japan produced a small amount of anatoxin-a, but no microcystins. One half of the strains of Microcystis produced microcystins and/or anatoxin-a. This is the first study showing Microcystis producing both anatoxin-a and microcystins.

Amino Acid Sequence↗
PubMed1993

Simple N-linked sugar chains are bound to the lutropin of the bullfrog rana catesbeiana.

The structures of Asn-linked sugar chains of the bullfrog (Rana catesbeiana) lutropin (LH) with different isoelectric points (pI 9.3 and pI 8.8) have been analyzed. The LH of pI 9.3, which is three times more active in Xenopus ovulation assays and radioreceptor assays with Xenopus testis than LH of pI 8.8, has Man-GlcNAc-GlcNAc and Man-Man-GlcNAc-GlcNAc as the major sugar chain components both at Asn-57 and 83 of the alpha-subunit. On the other hand, the alpha-subunit of the LH of pI 8.8 contained more mannose and phosphate bound at the nonreducing end of the sugar chains. This is the first study to identify the presence of a phosphate group bound to the mannose in LH. The structure of the major sugar chain bound to the beta-subunit was Man-Man-GlcNAc-(Fuc)GlcNAc at Asn-8 of the LH from both pIs. These sugar chains bound to the bullfrog LH are more simple than those of mammalian LH, which have N-acetyl-galactosaminylated biantennary oligosaccharides and more complicated sugar chains. The microheterogeneous pI of bullfrog LH is thus due to the different phosphate contents in the sugar chains bound to the alpha-subunit instead of sulfate groups which are found in mammalian lutropins.

Animals↗
PubMed1993

Isolation and characterization of two forms of Xenopus prolactin.

Two forms of highly purified prolactin (PRL) were obtained from pituitary glands of Xenopus laevis by extraction of acetone-dried powder with acid acetone and high-performance liquid chromatography on anion exchange, gel filtration, and reverse-phase columns. Purification was monitored by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analysis employing antiserum against bullfrog PRL. The Xenopus prolactins (xPRL-I and xPRL-II) thus obtained were shown to have similar molecular weights of 23,000 as determined by SDS-PAGE. The isoelectric points of xPRL-I and xPRL-II determined by isoelectric focusing were 5.6 and 5.3, respectively. Both hormones blocked T4-induced shrinkage of Xenopus tadpole tail fin in vitro. The amino acid compositions of the xPRLs resembled that of bullfrog PRL. The partial amino acid sequences of xPRL-I and of xPRL-II showed 78 and 68% homology with the comparable portion of the sequence of bullfrog PRL, respectively. Homology between xPRL-I and xPRL-II was 90%.

Amino Acid Sequence↗
PubMed1993

Smaller number of large myelinated fibers and focal myelin thickening in mutant quails deficient in neurofilaments.

The peripheral nervous system of a mutant of a Japanese quail deficient in neurofilaments (mutant) and of a normal Japanese quail (control) was morphometrically evaluated to characterize the morphological findings, especially those of the myelinated fibers of the mutant. In the proximal peroneal nerves, the frequency of the teased myelinated fibers showing the focal myelin thickening was higher in mutant than in control (P < 0.001) without obvious ongoing axonal degeneration and segmental demyelination. The total numbers of the myelinated fibers in the proximal and distal peroneal nerve, and in the tibial nerve branch to gastrocnemius muscle (pars medialis) were similar between control and mutant, although the number of the large myelinated fibers was less (P < 0.01) and the number of the small myelinated fibers was greater (P < 0.01) in mutant compared with control. The median diameters of neuronal cell bodies of the sacral dorsal root ganglia were similar in control and mutant. The percentages of light, dark and unclassified cells evaluated based on the histologic cytoplasmic features were also similar in control and mutant. Therefore, morphometric alterations were more pronounced in the peripheral myelinated nerve fibers compared with those in the cell bodies of the spinal dorsal root ganglia. We concluded that a smaller number of large myelinated fibers with a greater number of small myelinated fibers and the presence of focal myelin thickening are the main morphologic findings in this mutant, probably due to the arrest of radial growth or maturation of the axons of the myelinated fibers in the absence of ongoing myelinated fiber degeneration.

Animals↗
PubMed1993

Identification of alpha 1-adrenoceptor subtypes in the dog prostate.

The alpha 1-adrenoceptor subtypes of dog prostate were characterized in binding and functional experiments. In saturation experiments, [3H]prazosin bound to alpha 1-adrenoceptors with high affinity. In the displacement experiments, unlabelled prazosin and WB4101 biphasically inhibited the binding of 400 pM [3H]prazosin, suggesting the presence of at least two distinct affinity sites for prazosin or WB4101. The proportion of high-affinity sites was approximately 10%. HV723 also recognized two distinct affinity sites but the proportion of high-affinity sites was approximately 20%. From these results the presence of three distinct alpha 1-adrenoceptor subtypes was suggested: presumably subtypes alpha 1A (high affinity for prazosin and WB4101), alpha 1N (high affinity for only HV723) and alpha 1L (low affinity for the three antagonists) according to the recently proposed alpha 1-adrenoceptor subclassification. The density of subtype alpha 1L was much higher than that of subtypes alpha 1A and alpha 1N subtypes. In the functional experiments, prazosin, WB4101 and HV723 competitively antagonized the contractile response to noradrenaline with low affinities close to those estimated for the alpha 1L subtypes. These results suggest that the contractile response to noradrenaline in the dog prostate is mediated predominantly through alpha 1L subtype alpha-adrenoceptors.

Acetonitriles↗
PubMed1993

The prevalence and retention of lead pellets in Japanese quail.

Thirty-six Japanese quail (18 control birds, 18 lead-dosed birds) were used. The 18 quail were dosed with #4 lead weight that were orally inserted into the proventriculus. Delta-aminolevulunic acid dehydrase (ALAD) activity in erythrocytes in the dosed quail decreased 90% (p < 0.01) after one week as compared with the undosed quail. This inhibition of ALAD activity in erythrocytes indicates lead exposure. Radiographics were obtained at 0, 1, 4, 9, 22, and 32 days. The lead pellets remained in the gizzard and became smaller in 4 days. At day 22, after the lead treatment, in 8 quail of the treated quail 12, the lead pellets disappeared. At day 32, all lead pellets disappeared. These findings indicate that the ingested lead pellets are absorbed gradually in the intestine. The lead concentrations in the blood, liver, kidney, and femur of the lead-dosed quail were significantly higher than in the undosed quail until the 6th week. At week 2, the lead concentration of the proventriculus, gizzard, gizzard contents, duodenum, small intestine, and cecum in the dosed quail was significantly higher. Lead concentration of feces was significantly higher at weeks 2 and 4 (p < 0.01). Throughout this study, no lead pellets were found in the feces.

Animals↗