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Biomedical subjects

I Wakabayashi

Publications and source records attributed to I Wakabayashi.

At least 19 recordsLinked to original sources
PubMed1995

Inhibitory effects of cadmium ion on extracellular Ca(2+)-independent contraction of rat aorta.

In vitro effects of cadmium ion on vasoconstriction, particularly on vasoconstriction independent of extracellular Ca2+, were investigated using isolated rat aorta. Aorta incubation with CdCl2 (0.01, 0.1 mM) significantly attenuated contractile responses to KCl and phenylephrine in the medium containing normal Ca2+ (2.5 mM). The contractile response to phenylephrine in the presence of calcium channel antagonists, nifedipine (1 microM) or verapamil (1 microM), was markedly inhibited by CdCl2 (0.1 mM). In the medium without Ca2+, phenylephrine (10 microM) induced a phasic contraction, which was markedly inhibited by CdCl2 (0.1 mM). In the medium without Ca2+, phorbol 12-myristate 13-acetate (1 microM) and okadaic acid (10 microM) caused tonic contractile responses, which were strongly attenuated by CdCl2 (0.1 mM) pretreatment. Contractile response to sodium fluoride (5 approximately 15 mM) in the absence of extracellular Ca2+ was strongly attenuated by CdCl2 (0.1 mM) pretreatment. These results suggest that cadmium ion depresses an extracellular Ca(2+)-independent component of agonist-induced vasoconstriction by hindering an intracellular contractile mechanism(s).

Animals↗
PubMed1995

Endothelium-dependent relaxation resistant to NG-nitro-L-arginine in rat aorta.

Experiments were designed to determine whether cyclic GMP-independent relaxation is involved in the endothelium-dependent vascular relaxation response of rat aortic strip to acetylcholine. The relaxation response to acetylcholine in the presence of 3 x 10(-4) M NG-nitro-L-arginine was apparent when the precontraction was induced by norepinephrine at 5 x 10(-9) M or 10(-8) M. The relaxation response to acetylcholine resistant to NG-nitro-L-arginine was abolished by 10(-6) M atropine, 10 mM tetraethylammonium, or endothelium removal, but was not inhibited by 10(-5) M indomethacin, 3 x 10(-6) M oxyhemoglobin or 10(-5) M glibenclamide. The response was virtually abolished when the vascular strips had been preconstricted with 20 mM KCl. The increase in vascular cyclic GMP levels induced by 10(-5) M acetylcholine was completely abolished by 3 x 10(-4) M NG-nitro-L-arginine. These results suggest that acetylcholine-induced endothelium-dependent relaxation resistant to NG-nitro-L-arginine in rat aorta is unmasked when the precontractile force is caused by lower concentrations of norepinephrine and the relaxation is mediated by a cyclic GMP-independent mechanism, possibly an endothelium-derived hyperpolarizing factor.

Acetylcholine↗
PubMed1995

Caloric intake stimulates growth hormone secretion in food-deprived rats with anterolateral deafferentation of the medial basal hypothalamus or administered antiserum to somatostatin.

In rats, food deprivation inhibits episodic growth hormone (GH) secretion. On the basis of previous studies, we hypothesized that during a recovery from prolonged fasting, caloric intake stimulates the release of GH-releasing factor (GRF) and this process does not depend on the specific macronutrients in the meal, while protein in the meal acts to restore characteristic ultradian rhythmicity of GH secretion. To test this hypothesis, the effect of caloric intake on GH secretion was examined in fasted adult male Wistar rats devoid of somatostatin (SS) influence on GH secretion either by anterolateral deafferentation (ALC) of the medial basal hypothalamus (MBH) or administration of anti-SS goat serum (ASS). Rats were provided with an indwelling right atrial cannula and were deprived of food for 72 h. ALC was performed 2 weeks prior to the study. ASS was given i.v. 8 h and 7 h prior to refeeding, respectively. Serial blood specimens were collected every 10 min. In rats with ALC (ALC rats) or rats given ASS (ASS rats), the blood GH level revealed irregularly occurring small fluctuations, instead of the usual high bursts and low trough level. The baseline GH level and the mean GH level of fasted ALC rats or fasted ASS rats were significantly lower than those of fed ALC rats or fed ASS rats. Feeding the isocaloric mixed meal, the protein meal or the protein-deficient meal increased the GH pulse frequency, the pulse amplitude, the baseline GH level and the mean GH level in 72-h fasted ALC rats. These changes in GH secretory pattern persisted during the period of observation and were independent of the type of meal ingested. Following feeding the mixed meal, similar changes in the GH secretory pattern demonstrated in 72-h fasted ALC rats were also observed in 72-h fasted ASS rats, suggesting that the stimulation of GH secretion following caloric intake is not limited to ALC rats. Since the influence of SS on GH secretion has been largely eliminated in ALC or ASS rats, it is highly unlikely that the augmentation of GH secretion following feeding after prolonged food deprivation was the consequence of inhibition of SS secretion. Although GRF measurement was not performed, it is conceivable that the signal of caloric intake is conveyed to the MBH and acts to stimulate GRF release.

Animals↗
PubMed1994

Effect of D-Ala-D-beta Nal-Ala-Trp-D-Phe-Lys-NH2 (KP-102) on GH secretion in urethan-anesthetized rats.

The effect of a newly developed growth hormone (GH)-releasing hexapeptide (KP-102) on GH secretion was studied in urethan-anesthetized adult male rats. Although KP-102 alone exerted a small influence on GH secretion, it produced a large plasma GH response in the presence of exogenous GH-releasing factor (GRF). During the continuous infusion of GRF, the somatotropes became refractory to a large bolus dose of GRF, but KP-102 induced a marked increase of plasma GH. The GH response to KP-102 alone or KP-102 with GRF was significantly augmented when antiserum to somatostatin (ASS) was previously administered. Although KP-102 and GRF acted synergistically on GH secretion in control animals, they acted additively in ASS-administered rats. The KP-102 effect on plasma GH was significantly attenuated in control animals and ASS-administered rats by prior i.v. injection of antiserum to GRF. Taken together, KP-102 stimulates GH secretion dependent on GRF and appears to act synergistically with GRF by antagonizing the SS effect.

Animals↗
PubMed1994

[Effects of ethanol on isometric tonus of guinea pig gall bladder strips].

Using gall bladder strips isolated from guinea pigs, effects of ethanol treatment in vitro and in vivo on gall bladder tonus were studied. In the control (glucose administrated) group, the reactivity and sensitivity of ACh contraction of the strips were attenuated by ethanol at the concentration of 200 mM and over, while those of CCK contraction was attenuated at the concentration of 200 mM over. On the other hand, in the strips from guinea pigs chronically administered 3% ethanol, both ACh- and CCK-induced contractions were inhibited by the ethanol at the concentrations of 200 mM over. It is known that CCK and ACh are main humoral factors in situ which influence gall bladder tone, and physiologically attainable concentrations of ethanol are below 100 mM. Therefore, it is concluded that the physiological concentrations of ethanol unlikely affect the motility of gall bladder in vivo.

Animals↗
PubMed1993

Effect of parenteral administration of selected nutrients and central injection of gamma-globulin from antiserum to neuropeptide Y on growth hormone secretory pattern in food-deprived rats.

Serial changes in growth hormone (GH) secretory pattern during 72 h food deprivation and in response to refeeding after 72 h food deprivation were observed in adult male Wistar rats. In addition, the effects of intravenous administration of glucose, fatty acids or amino acids and central injection of gamma-globulin from antiserum to human neuropeptide Y (NPY) on the GH secretory pattern were examined in 72 h food-deprived rats. Rats were provided with chronic indwelling right atrial cannula and serial blood specimens were withdrawn via the cannula every 10 min using an automatic blood-sampling device. The GH secretory pattern was analyzed using a Pulsar computer program. In fed rats, episodic GH secretion with an amplitude exceeding 350 ng/ml occurred at 170-min intervals and intervening trough GH levels were less than 10 ng/ml. During the 72 h food deprivation, the amplitude of pulsatile GH secretion decreased progressively without altering the pulse frequency. When 72 h food-deprived rats were refed lab chow, the pulse frequency and the pulse amplitude increased rapidly and lasted for 6-8 h. Normal pulsatile GH secretion resumed by 10-12 h after refeeding following the 72 h food deprivation. To identify the specific nutrient (i.e. glucose, fatty acids or amino acids) serving as the signal causing restoration of the central drive to GH secretion, glucose solution (2 or 6 kcal), lipid emulsion (2 or 6 kcal) or amino acid solution (2 kcal) was administered intravenously to the 72 h food-deprived rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1993

Somatostatin reduces transcription of the growth hormone gene in rats.

To examine whether somatostatin (SS) exerts influences on the steady state levels of GH-releasing factor (GRF), the effect of SS on GH gene transcription was examined in rats. This approach was used because it has been shown that GRF stimulates GH gene transcription independent of GH release, and SS does not inhibit basal or GRF-stimulated GH gene transcription. Therefore, it is assumed that an effect of SS on GH gene transcription would be mediated by a change in GRF levels. Adult female Sprague-Dawley rats were provided with right atrial cannulae. Studies were performed using unanesthetized rats. Pituitary GH gene transcription was measured by transcription assay. An iv administration of antiserum to rat GRF 150 min previously significantly decreased GH gene transcription compared with that in control rats given normal goat serum. A continuous infusion of SS (300 micrograms/kg.h) via the cannula for 150 min significantly decreased GH gene transcription compared with that in control rats receiving 0.9% NaCl. When GRF (3 micrograms/kg.h) was given simultaneously with SS (300 micrograms/kg.h), GH gene transcription increased significantly compared with that in rats receiving SS infusion alone. After the withdrawal of SS infusion, GH gene transcription rapidly and significantly increased. The data suggest that SS reduces the steady state levels of GRF.

Animals↗
PubMed1993

Cerebral aneurysm associated with multiple endocrine neoplasia, type 1--case report.

Cerebral aneurysm associated with pituitary adenoma and other endocrine dysfunctions occurred in a 45-year-old female suffering from multiple endocrine neoplasia, type 1 (Wermer's syndrome). She died of subarachnoid hemorrhage secondary to rupture of the aneurysm. Pituitary adenoma and/or other endocrine dysfunctions associated with multiple endocrine neoplasia, type 1 may be a factor in the aneurysm formation.

Adenoma↗
PubMed1992

Effect of chromium administration on glucose tolerance in stroke-prone spontaneously hypertensive rats with streptozotocin-induced diabetes.

The present study was conducted to assess the effect of chromium (Cr) administration on glucose tolerance in insulin-dependent diabetes that accompanies hypertension. Four rat groups were used: stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar Kyoto rats (WKY) with and without streptozotocin (SZ, 40 mg/kg)-induced diabetes. Each group of rats was subdivided to the Cr-dose group and the control group. The Cr-dose group, which was intraperitoneally administered Cr solution (20 micrograms trivalent chromium/kg body weight/d for 4 weeks), and the control group (saline) were studied for plasma glucose and plasma insulin during intraperitoneal glucose tolerance test (IPGTT) and insulin action by isolated adipocytes. For diabetic SHRSP showing the highest plasma glucose and lowest plasma insulin among the four groups, Cr administration led to the greatest reduction in plasma glucose without a significant effect on plasma insulin during IPGTT. For each diabetic WKY and normal SHRSP and WKY, those given Cr showed lower levels of plasma glucose with lower levels of plasma insulin than the controls. For diabetic SHRSP, glucose uptake by isolated adipocytes in the Cr-dose group was higher than that in the control group. This effect of Cr administration involved enhancement of insulin responsiveness and sensitivity, attributed to enhanced affinity of the insulin receptor. A similar tendency was observed for diabetic WKY. However, for normal SHRSP and WKY, the increase in glucose uptake due to Cr administration coincided only with enhanced insulin responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Transcriptional activity of a mutant thyroid hormone receptor beta in a family with generalized resistance to thyroid hormone.

We previously reported a family with generalized resistance to thyroid hormone (GRTH) which had a point mutation with codon 448 CCT (proline) being converted to ACT (threonine) in the thyroid hormone receptor (TR) beta. To characterize functional properties of the mutant TR beta, transient expression studies were performed in COS cells. A double stranded oligonucleotide encompassing thyroid hormone response element (TRE) derived from the rat GH gene was synthesized. We constructed chloramphenicol acetyl transferase (CAT) plasmid containing the thymidine kinase promoter under the control of the rat GH TRE. T3 induction of CAT activity by the mutant TR beta was significantly reduced as compared with that of the normal TR beta. This was observed in the presence of 0.5-50 nM T3, but not at 500 nM T3. When the normal and mutant TR beta were cotransfected, the mutant TR beta inhibited gene activation regulated by the normal TR beta. However, a high molar excess was necessary to significantly inhibit the function of the normal receptor. Additionally, the binding of in vitro synthesized mutant TR beta to TRE was preserved.

Animals↗
PubMed1992

Effect of aging on contractile response to KCl, norepinephrine and 5-hydroxytryptamine in isolated human basilar artery.

1. We investigated the effect of aging on contractile response in human basilar artery. 2. The maximal contraction caused by KCl, norepinephrine and 5-hydroxytryptamine decreased with age. 3. ED50 value for norepinephrine or 5-hydroxytryptamine did not correlate with age. 4. These results suggest that the decrease in contractile response is due to nonspecific changes in the medial structure of the artery.

Adolescent↗
PubMed1992

Ammonium ion increases the tone of rat portal vein.

1. The effect of ammonium ion on vascular tone was investigated using the portal vein isolated from rat. 2. Ammonium chloride at 10-90 mM induced a contractile response. 3. Spontaneous twitch contraction of portal strips was augmented by ammonium chloride at 10-60 mM. 4. Ammonium chloride-induced contraction was abolished in calcium-free solution or in the presence of 1 microM nifedipine. 5. Methylamine (60 mM) also induced a contractile response and augmented the spontaneous twitch contraction in rat portal vein. 6. After withdrawal of ammonium chloride or methylamine from the organ bath solution, the spontaneous twitch contraction was strongly inhibited. 7. These results suggest that ammonium compounds increase vascular tone by causing influx of extracellular calcium through the voltage-dependent calcium channel and intracellular alkalinization is involved in this process.

Ammonia↗
PubMed1992

Vasorelaxant effect of trapidil on human basilar artery.

We have investigated the vasorelaxant effect of trapidil on human isolated basilar artery. Trapidil (10(-5)-10(-4) M) dose-dependently caused relaxation in vascular strips with or without endothelium, with no significant difference between the two types of strips. The relaxation responses were not inhibited by atropine, propranolol or methylene blue. Trapidil increased the concentration of 6-keto-PGF1 alpha, a prostacyclin degradation product, released from an artery ring in the incubation medium, but trapidil-induced relaxation was not inhibited by indomethacin. Pretreatment of vascular strips with 10(-5) M trapidil increased the relaxation responses to forskolin and dibutyryladenosine cyclic monophosphate but not to sodium nitroprusside or 8-bromoguanosine cyclic monophosphate. Trapidil induced a significant increase in the cAMP concentration but not in the cGMP concentration in artery strips. These results suggest that the relaxation response to trapidil is not caused by prostacyclin release or an increase in cGMP in the smooth muscle, but possibly by an increase in the cAMP levels, probably via an inhibitory effect on cAMP phosphodiesterase.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Impairment of endothelium-dependent relaxation in human basilar artery after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The goal of this study was to determine the alterations in vascular reactivity of human basilar artery after subarachnoid hemorrhage. METHODS: Human basilar arteries were obtained from subjects who died within 1 day after subarachnoid hemorrhage and control subjects who died from causes other than brain involvement. Basilar artery strips were suspended for isometric tension recording in Krebs-Ringer solution. Morphometric study was also carried out on paraffin-embedded sections stained with van Gieson's elastica stain of preselected sites from the basilar arteries. The intimal and medial area and the intimal index ([intimal area/area circumscribed by internal elastic lamina] x 100) were evaluated. RESULTS: Contractile responses to KCl, norepinephrine, and 5-hydroxytryptamine did not differ between subarachnoid hemorrhage and control groups. The endothelium-dependent relaxation responses to thrombin, bradykinin, and calcium ionophore A23187 were less for the subarachnoid hemorrhage group than for the control group. However, the endothelium-independent response to sodium nitroprusside of the subarachnoid hemorrhage group did not differ from that of the control group. Morphometric measurements were comparable between the two groups. CONCLUSIONS: These results suggest that the decreased relaxation responses to thrombin and bradykinin occur at the level of endothelial cells and not smooth muscle cells and that decreased relaxation may be involved in delayed vasospasm after subarachnoid hemorrhage. Although the decreased relaxation was observed within 1 day after subarachnoid hemorrhage, a period in which delayed spasm does not occur, this time difference may be dependent on the severity of bleeding after rupture of an aneurysm.

Adult↗
PubMed1992

Systemic administration of recombinant human growth hormone induces expression of the c-fos gene in the hypothalamic arcuate and periventricular nuclei in hypophysectomized rats.

The neuronal expression of the protooncogene c-fos could serve as a marker of neural activity. To identify the brain sites responding to GH, rat brains after systemic administration of recombinant human GH (rhGH) were processed for hybridization histochemistry for c-fos mRNA. Adult male Wistar rats were hypophysectomized 10 days before rhGH administration. After hypophysectomy, rats received sc cortisone acetate (0.5 mg/kg BW) and L-T4 (20 microgram/kg BW) daily. Four international units (1.33 mg) of rhGH were given iv through an indwelling right atrial cannula. Vehicle was administered to control animals. The rhGH treatment was accompanied by expression of the c-fos gene in the arcuate nucleus (ARC) of the hypothalamus. The accumulation of the c-fos mRNA was transient, reaching maximum values at 60 min and decreasing thereafter to reach control levels within 120 min after rhGH injection. Among control animals, c-fos gene expression was not detected in the ARC. The c-fos mRNA was also detected in the paraventricular nucleus after rhGH administration; however, it was comparable to that in control animals. When rhGH was administered twice at 40-min intervals, c-fos gene expression was induced in the periventricular nucleus (PeV) as well as the ARC 40 min after the second rhGH injection. Throughout the studies, c-fos mRNA was not detected other than in the ARC, paraventricular nucleus, and PeV in the hypothalamus. In the ARC, distribution of the cells expressing the c-fos gene appears to overlap at least in part with somatostatin (SS) mRNA-containing cells. In the PeV, it appeared to correlate generally with the distribution of SS mRNA-containing cells. The data suggest that GH feeds back on neurons of hypothalamic PeV and ARC expressing SS mRNA, and that c-fos expression is involved in the feedback mechanism.

Animals↗
PubMed1992

Expression of growth hormone (GH)-releasing factor gene in GH-producing pituitary adenoma.

Pituitary cells synthesize various neuropeptides that influence pituitary hormone secretion. GH-releasing factor (GRF) may also be produced by normal or pituitary tumor cells. We examined GRF gene expression in pituitary tumors. Standard techniques for the analysis of GRF gene expression did not appear to be suitable. Highly sensitive reverse transcription coupled to polymerase chain reaction was used. Specimens of pituitary adenoma were obtained by transsphenoidal adenomectomy from six patients with acromegaly and three patients with no clinical evidence of pituitary hormone overproduction; non-functioning adenoma. Pituitary glands were collected at autopsy from three patients who died from nonendocrine disorders. A specific GRF gene transcript was detected in five out of six GH-producing pituitary adenomas, whereas this was not found in three separate specimens of nonfunctioning pituitary adenoma or anterior and posterior pituitary tissue. The data suggest that GRF is synthesized as an intrinsic product in human GH-producing pituitary adenoma.

Acromegaly↗
PubMed1992

A point mutation in the 3,5,3'-triiodothyronine-binding domain of thyroid hormone receptor-beta associated with a family with generalized resistance to thyroid hormone.

A tight linkage between generalized resistance to thyroid hormone (GRTH) and the thyroid hormone receptor-beta (TR beta) gene is indicated. We evaluated a family with GRTH for the TR beta gene. We found that a new point mutation, consisting of a cytosine to adenine replacement at nucleotide position 1642, resulted in substitution in codon 448 in the T3-binding domain of TR beta. This base substitution was found in only one allele of affected members, but not in unaffected members of the family. The in vitro translation products of this mutant TR beta gene demonstrated significantly reduced T3-binding affinity. Previously, others have reported a kindred with GRTH, in that the same codon was subjected to proline to histidine replacement due to a mutation consisting of a cytosine to adenine replacement at nucleotide position 1643. There appeared to be a significant phenotypic difference between our kindred and that described by others.

Alleles↗