Biomedical subjects

T Takenaka

Publications and source records attributed to T Takenaka.

At least 19 recordsLinked to original sources

PubMed1998

Hypoxic adaptation of the peptidergic innervation in the rat carotid body.

The abundance of substance P (SP)-, calcitonin gene-related peptide (CGRP)-, vasoactive intestinal polypeptide (VIP)-, and neuropeptide Y (NPY)-immunoreactive nerve fibers in the carotid body was compared between normoxic and chronically hypoxic rats (10% O2 and 3.0-4.0% CO2 for 3 months). The immunoreactive fibers appeared as thin processes with many varicosities, and were distributed mainly around the vasculatures. In the normoxic control carotid body, NPY fibers were more numerous than VIP, CGRP, and SP fibers. In the chronically hypoxic rats, the carotid body was enlarged several fold, and the mean absolute number of VIP and NPY fibers was 3.88 and 2.22 times higher than in the normoxic carotid body, respectively, although that of SP and CGRP fibers was not changed. When expressed as density per unit area of the parenchyma, the density of SP and CGRP fibers in the chronically hypoxic carotid body decreased significantly to under 50%, the density of VIP fibers increased significantly 1.80 times, and the density of NPY fibers were unchanged. Immunoreactivity for four neuropeptides was not found in the glomus cells of normoxic or chronically hypoxic carotid bodies. These results suggest that altered peptidergic innervation of the chronically hypoxic carotid body is one feature of hypoxic adaptation. Because these neuropeptides are vasoactive in nature, altered carotid body circulation may contribute to modulation of the chemosensory mechanisms by chronic hypoxia.

Adaptation, Physiological↗

PubMed1998

Mechanosensitive cation channels mediate afferent arteriolar myogenic constriction in the isolated rat kidney.

1. In order to assess ionic mechanisms mediating renal afferent arteriolar myogenic constriction, experiments were performed using isolated perfused hydronephrotic rat kidneys. 2. Increasing pressure progressively constricted the afferent arteriole (-0.26 +/- 0.02% mmHg-1, n = 21, r = 0.97). Gadolinium (10 microM), a mechanosensitive cation channel blocker, abolished this myogenic constriction. However, high potassium media (30 mM) constricted the afferent arteriole in the presence of gadolinium. 3. Lowering extracellular sodium concentration gradually attenuated afferent arteriolar myogenic constriction. In the perfusate containing 50 mM sodium, the myogenic response was arrested. 4. Afferent arteriolar myogenic constriction was prevented in calcium-free perfusate or by the L-type calcium channel blocker diltiazem (10 microM). 5. Our present findings provide evidence that increasing pressure gates mechanosensitive cation channels on the afferent arteriole, thereby eliciting membrane depolarization and activating voltage-dependent calcium channels.

Animals↗

PubMed1998

Development of obstructive hypertrophic cardiomyopathy from nonobstructive hypertrophic cardiomyopathy.

A rare case of obstructive hypertrophic cardiomyopathy (HC) with mitral regurgitation (MR) is reported, which developed over 7 years from nonobstructive HC in an elderly woman. Systolic anterior motion of the anterior mitral leaflet was the most likely cause of the outflow obstruction and mitral valve replacement combined with septal myectomy resulted in complete abolition of the outflow tract gradient and MR.

Aged↗

PubMed1998

p53-independent induction of WAF1/Cip1 is correlated with osteoblastic differentiation by vitamin D3.

1Alpha,25(OH)2 vitamin D3 (1,25(OH)2D3) can induce differentiation of osteoblastic cells by arresting the cell cycle at G1. The p53-inducible gene, WAF1/Cip1, is one of the inhibitors of cyclin-dependent kinases and can inhibit the phosphorylation of retinoblastoma protein (pRB), thereby keeping pRB functionally active. Here we show that in a p53-null human osteoblastic osteosarcoma MG-63 cell line, 10 nM of 1,25(OH)2D3 completely inhibits cell growth and increases alkaline phosphatase activity, which suggests the induction of osteoblastic differentiation. We also found a p53-independent increase of WAF1/Cip1 mRNA and promoter activation by 1,25(OH)2D3. On the other hand, the expression and the promoter activity of the RB gene decreased after treatment with 1,25(OH)2D3 during the differentiation of MG-63 cells. Our results suggest that the p53-independent WAF1/Cip1 induction by 1,25(OH)2D3 is important for osteoblastic differentiation of MG-63 cells.

Calcitriol↗

PubMed1998

Changes in the distribution of nitric oxide synthase immunoreactive nerve fibers in the chronically hypoxic rat carotid body.

The distribution of nitric oxide synthase (NOS) immunoreactive nerve fibers in the carotid body was compared between normoxic and chronically hypoxic rats (10% O2 and 3.0-4.0% CO2 for 3 months). NOS immunoreactive fibers appeared as thin processes with many varicosities. They were distributed predominantly around small arteries and arterioles, and around clusters of glomus cells. When expressed by the density of varicosities per unit area in the parenchyma, the density of NOS fibers associated with the vasculature and with the glomus cells in the chronically hypoxic carotid bodies was significantly decreased. Because nitric oxide (NO) is an inhibitory neuronal messenger in the normoxic carotid body, the present findings suggest that the sensory mechanisms in the hypoxic carotid body may be involved in 'disinhibition' resulting from reduced NO synthesis.

Animals↗

PubMed1998

Mitogenic activity of endothelin on human cultured prostatic smooth muscle cells.

The effects of endothelins on human prostatic smooth-muscle cell growth were examined. Endothelin-1 and endothelin-3 induced a concentration-dependent increase in DNA synthesis and also promoted cell growth. Use of subtype selective antagonists BQ-123 ((cyclo(D-Trp-D-Asp(ONa)-Pro-D-Val-Leu); endothelin ET(A) receptor selective) and BQ-788 ((N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methyl Leu-D-Trp-(COOMe)-D-Nle-ONa); endothelin ET(B) receptor selective), indicated that mitogenic effects of endothelin were mediated through activation of both endothelin ET(A) and ET(B) receptors. The mitogenic effects of endothelin-1 and endothelin-3 were significantly inhibited by pretreatment of the cells with pertussis toxin. However, mitogenesis due to basic fibroblast growth factor was not affected. In conclusion, endothelin has mitogenic effects on human prostatic smooth muscle cells through activation of both endothelin ET(A) and ET(B) receptors via different signalling pathways from basic fibroblast growth factor. This may contribute to smooth muscle hyperplasia associated with benign prostatic hyperplasia.

Aged↗

PubMed1998

Transient appearance of substance P-like immunoreactivity in the granular convoluted tubules of the male mouse submandibular gland: light- and electron-microscopic studies.

The time of appearance and distribution of substance P (SP)-like immunoreactivity in the granular convoluted tubule cells of the developing male mouse submandibular glands were examined, and the subcellular localization of SP-like immunoreactivity was investiagted by electron microscopy. At 25 days of age, SP-like immunoreactivity was first detected in the supranuclear cytoplasm of the granular convoluted tubule cells, which occurred either singly or in small clusters. At 30 and 35 days of age, granular convoluted tubule cells with SP-like immunoreactivity were more numerous than in the earlier stages, as the volume ratio of the cells increased. Not all granular convoluted tubule cells demonstrated SP-like immunoreactivity. The number of cells with SP-like immunoreactivity decreased at 60 days of age, and these cells had completely disappeared at 90 days of age. Most, but not all, secretory granules in the granular convoluted tubule cells were strongly labeled with gold particles, indicating that the subcellular site of SP-like substance is in the secretory granules within the cells. The findings suggest that the physiological role of the SP-like substance secreted from the GCT cells is restricted to the early postnatal stages, and that it may be involved in the development of the oral mucosa or digestive tract as a trophic factor.

Animals↗

PubMed1998

Ex vivo occupancy by tamsulosin of alpha1-adrenoceptors in rat tissues in relation to the plasma concentration.

At 0.5-12 h after oral administration of tamsulosin (2.3 micromol/kg) in rats, there was a significant decrease in specific [3H]prazosin binding in the prostate as compared to the control value. The greater decrease occurred in the submaxillary gland. The effect of tamsulosin was mainly due to a marked reduction of [3H]prazosin binding sites (Bmax) rather than to an increase in the dissociation constant (Kd). In contrast, there was only a slight decrease or no change in the [3H]prazosin binding in the spleen, heart, and cerebral cortex of tamsulosin-administered rats at 0.5-12 h. Oral administration of terazosin (21.7 micromol/kg) significantly increased Kd values for [3H]prazosin binding with little effect on Bmax values in the rat prostate at 3 and 6 h. The greater increases in Kd values were observed in the submaxillary gland, spleen and heart at 0.5-12 h. Terazosin had a slight effect on Kd values for the cerebral cortical [3H]prazosin binding. Tamsulosin was absorbed rapidly after oral administration at a dose of 2.3 micromol/kg in rats, and at 6 h, plasma concentration decreased markedly to approximately one-twentieth of the 0.5 h peak level. alpha1-Adrenoceptor occupancy was estimated as a percentage of decrease in Bmax values for [3H]prazosin binding in tissues of tamsulosin-treated rats compared with control rats. The alpha1-adrenoceptor occupancy by tamsulosin in the prostate and submaxillary gland occurred rapidly in parallel with the rise in plasma concentration of tamsulosin, and lasted for over 12 h despite the marked decrease in plasma concentration. Consequently, it is suggested that tamsulosin produces more selective and sustained occupancy in vivo of alpha1-adrenoceptors in the submaxillary gland and prostate of rats than in other tissues.

Administration, Oral↗

PubMed1998

Effect of YM435, a novel dopamine DA1 receptor agonist, in a canine model of acute congestive heart failure.

1. The effects of YM435, a dopamine DA1 receptor agonist, were evaluated in a canine model of acute congestive heart failure. 2. The model was induced in open-chest anesthetized dogs by left anterior descending coronary artery ligation, volume loading, and intravenous infusion of angiotensin II. This resulted in a moderate and stable congestive heart failure characterized by reduction in cardiac output and increases in left ventricular end-diastolic pressure and total peripheral vascular resistance. 3. Intravenous infusion of YM435 (1 microgram/kg/min) significantly decreased left ventricular end-diastolic pressure, total peripheral vascular resistance and mean blood pressure and significantly increased cardiac output and renal blood flow in this model. 4. These results indicate that intravenous infusion of YM435 can improve hemodynamics and cardiac function in a canine model of acute congestive heart failure. YM435 may be a useful therapeutic agent for the treatment of congestive heart failure.

Animals↗

PubMed1998

Effect of YM435, a dopamine DA1 receptor agonist, in a canine model of ischemic acute renal failure.

1. The effects of (-)-(S)-4-(3,4-dihydroxyphenyl)- 1,2,3,4-tetrahydroisoquinoline-7,8-diol monohydrochloride monohydrate (YM435), a dopamine DA1 receptor agonist, were evaluated in a canine model of ischemic acute renal failure (ARF). 2. ARF was induced by clamping the left renal artery for 1 hr and subsequent reperfusion of the left kidney in anesthetized uninephrectomized dogs. 3. After 1-hr complete renal artery occlusion, an intravenous infusion of either YM435 (0.3 microg/kg/ min) or 0.9% saline (vehicle) was begun and continued for 1 hr. 4. In the vehicle group, renal ischemia markedly decreased glomerular filtration rate, urine flow and urinary sodium excretion. The YM435 group was characterized by significant recoveries in glomerular filtration rate, urine flow, and urinary sodium excretion as compared with the vehicle group. 5. These results indicate that YM435 can facilitate recovery in glomerular filtration rate, urine flow, and urinary sodium excretion in a canine model of ARF induced by ischemia. YM435 may be useful in the preservation of renal function in ischemia-induced ARF.

Acute Disease↗

PubMed1998

Substance P- and calcitonin gene-related peptide-containing nerve fibers in the nasal mucosa of chronically hypoxic rats.

The distribution of substance P-immunoreactive and calcitonin gene-related peptide-immunoreactive nerve fibers in the nasal mucosa was compared between normoxic and chronically hypoxic rats (10% O2 and 3.0-4.0% CO2 for 3 months). In the normoxic nasal mucosa, substance P- and calcitonin gene-related peptide-immunoreactive nerve fibers were found within and under the epithelium and around the glands and blood vessels in the lamina propria. These immunoreactive fibers have many varicosities. In the chronically hypoxic nasal mucosa, the relative density of intra- and subepithelial substance P-immunoreactive and calcitonin gene-related peptide-immunoreactive fibers and those in the lamina propria was higher than in normoxic mucosa. The length of substance P-positive fibers within the chronically hypoxic olfactory and respiratory epithelium was 1.66 and 2.45 times higher than within the normoxic epithelium, respectively. The length of calcitonin gene-related peptide-immunostained fibers within the chronically hypoxic olfactory and respiratory epithelium was 1.56 and 1.84 times higher, respectively. Because substance P and calcitonin gene-related peptide are the predominant signal peptides of primary sensory neurons, the increased number of these fibers may represent enhanced sensory mechanisms in the hypoxic nasal mucosa. In addition, considered together with the findings in chronically hypoxic tracheal mucosa, the increased density of intraepithelial fibers containing substance P and calcitonin gene-related peptide suggests that this is a predominant feature of hypoxic adaptation throughout the upper and lower respiratory tracts.

Animals↗

PubMed1998

Thrombotic microangiopathy of hyperacute onset after autologous peripheral blood stem cell transplantation in malignant lymphoma.

Bone marrow transplant-associated thrombotic microangiopathy (BMT-TM), usually associated with thrombocytopenia, microangiopathic haemolytic anaemia (MAHA) and renal insufficiency, has been reported to occur approximately 5-6 months after BMT. We report a case of relapsed malignant lymphoma complicated by BMT-TM of hyperacute onset, which has never been described in the literature. Our patient, a 52-year-old male, developed MAHA with gross haematuria, thrombocytopenia, lactate dehydrogenase elevation and renal insufficiency 2 days after autologous PBSC transplantation following high-dose chemotherapy. Supportive treatment, ie glucocorticoid, fresh frozen plasma and haemodiafiltration were given, and thereafter the BMT-TM gradually improved. In heavily pretreated patients, caution should be exercised for possible occurrence of the BMT-TM of hyperacute onset.

Hematopoietic Stem Cell Transplantation↗

PubMed1998

Immunohistochemical localisation of regulatory neuropeptides in human circumvallate papillae.

The occurrence and distribution of neuropeptide-containing nerve fibres in the human circumvallate papillae were examined by the peroxidase-antiperoxidase immunolocalisation method using surgical specimens that had not been subjected to radiotherapy, and the abundance of neuropeptide-containing fibres was expressed as the percentage of total nerve fibres demonstrated by protein gene product (PGP) 9.5 immunoreactivity for a quantitative representation of these peptidergic fibres. Substance P (SP) and calcitonin gene-related peptide (CGRP) immunoreactive (IR) nerve fibres were densely distributed in the connective tissue core of the circumvallate papillae, and some SP and CGRP-IR fibres were associated with the taste buds. A moderate number of vasoactive intestinal polypeptide (VIP)-IR fibres and a few galanin (GAL)-IR fibres were also seen in the connective tissue core and subepithelial layer. There were, however, no VIP-IR or GAL-IR fibres associated with the taste buds. Neuropeptide Y (NPY)-IR fibres were few and were associated with the blood vessels. Within the epithelium of the circumvallate papillae, no peptidergic fibres were found, although a number of PGP 9.5-IR fibres were detected. The abundance of SP, CGRP, VIP, and GAL-IR fibres expressed as the percentage of total PGP 9.5 IR fibres was 25.35+/-3.45%, 22.18+/-3.26%, 10.23+/-1.18%, and 4.12+/-1.05%, respectively. The percentage of NPY-IR fibres was below 3%. In a deeper layer of the papillae, a few VIP, GAL, and NPY-IR ganglion cells were found, and VIP immunoreactivity was detected in a few cells of the taste buds. There was no somatostatin, leucine enkephalin, or methionine enkephalin immunoreactivity in the circumvallate papillae. These results suggest that the dense SP and CGRP-IR fibres within the connective tissue core of the human circumvallate papillae may be involved in the deep sensation of the tongue.

Adult↗

PubMed1998

Enhanced angiotensin II stimulates renal disorders in transgenic Tsukuba hypertensive mice.

Tsukuba hypertensive mice (THMs) are transgenic mice carrying human renin-angiotensin system (RAS) genes. The aim of this study is to evaluate whether renal disorders are present in THMs. Twenty-week-old THMs and C57BL/6 mice (C57s) were used for this study. Each group consisted of 8 mice. Systolic blood pressure, urinary volume, water intake and urinary albumin excretion were measured in each mouse. Each mouse was then euthanized, and the renal glomerulosclerosis index and glomerular size were measured. Systolic blood pressure of THMs was about 40 mmHg higher than that of C57s. Urinary volume, water intake and urinary albumin excretion were significantly higher in THMs than in C57s. The renal glomerulosclerosis index and glomerular size were also significantly higher in THMs than in C57s. These results suggested that an enhanced renin-angiotensin system, including its hypertensive effects, stimulates albuminuria, renal glomerulosclerosis and glomerular hypertrophy in THMs.

Angiotensin II↗

PubMed1998

Tissue angiotensin II concentration in the heart and kidneys in transgenic Tsukuba hypertensive mice.

Tsukuba hypertensive mice (THM) are transgenic mice carrying both human renin and angiotensinogen genes, and possessing an overexpressing human renin-angiotensin system. The aim of this study is to evaluate the angiotensin II concentration in the heart and kidney in THM. Twenty-week-old male THM and control C57BL/6 mice (C57) were used. Each group consisted of 3 mice. For each mouse, systolic blood pressure, heart to body weight ratio, renal glomerular sclerosis index and angiotensin II concentration in the heart and kidney were measured. Systolic blood pressure of THM was about 40 mmHg higher than that of C57. Heart to body weight ratio and renal glomerular sclerosis index were significantly higher in THM than those in C57. The angiotensin II concentration in THM was about 4 times higher in the heart and about 5 times higher in the kidney compared with that in C57. These results suggest that accelerated tissue angiotensin II production, significant cardiac hypertrophy and renal glomerular sclerosis all occur because of hypertension.

Angiotensin II↗

PubMed1998

Propofol-induced increase in vascular capacitance is due to inhibition of sympathetic vasoconstrictive activity.

BACKGROUND: Venodilation is thought to be one of the mechanisms underlying propofol-induced hypotension. The purpose of this study is to test two hypotheses: (1) propofol increases systemic vascular capacitance, and (2) the capacitance change produced by propofol is a result of an inhibition of sympathetic vasoconstrictor activity. METHODS: In 33 Wistar rats previously anesthetized with urethane and ketamine, vascular capacitance was examined before and after propofol infusion by measuring mean circulatory filling pressure (Pmcf). The Pmcf was measured during a brief period of circulatory arrest produced by inflating an indwelling balloon in the right atrium. Rats were assigned into four groups: an intact group, a sympathetic nervous system (SNS)-block group produced by hexamethonium infusion, a SNS-block + noradrenaline (NA) group, and a hypovolemic group. The Pmcf was measured at a control state and 2 min after a bolus administration of 2, 10, and 20 mg/kg of propofol. RESULTS: The mean arterial pressure (MAP) was decreased by propofol dose-dependently in intact, hypovolemic, and SNS-block groups, but the decrease in MAP was less in the SNS-block group (-25%) than in the intact (-50%) and hypovolemic (-61%) groups. In the SNS-block + NA group, MAP decreased only at 20 mg/kg of propofol (-18%). The Pmcf decreased in intact and hypovolemic groups in a dose-dependent fashion but was unchanged in the SNS-block and SNS-block + NA groups. CONCLUSIONS: The results have provided two principal findings: (1) propofol decreases Pmcf dose-dependently, and (2) the decrease in Pmcf by propofol is elicited only when the sympathetic nervous system is intact, suggesting that propofol increases systemic vascular capacitance as a result of an inhibition of sympathetic nervous system.

Anesthetics, Intravenous↗

PubMed1998

Distinct effects of tetragastrin, histamine, and CCh on rat gastric mucin synthesis and contribution of NO.

Although gastrin, histamine, and carbachol (CCh) accelerate gastric mucin metabolism, information about their target cells of mucin production is lacking. To clarify this, we examined the effects of these stimulants, including the possible participation of nitric oxide (NO), on mucin biosynthesis in distinct sites and layers of rat gastric mucosa. Pieces of tissue obtained from the corpus and antrum were incubated in a medium containing radioactive precursors and each stimulant, with or without NO synthase (NOS) inhibitor. Distribution of NOS was compared with that of the specific mucins by immunostaining using specific antiserum and monoclonal antibodies. In the full-thickness corpus mucosa, tetragastrin enhanced [3H]glucosamine incorporation into mucin but had no effect on [14C]threonine incorporation. Both histamine and CCh dose dependently increased 3H- and 14C-labeled corpus mucin. Only CCh stimulated antral mucin biosynthesis. CCh stimulation was noted in the corpus mucosa after removal of surface mucous cells, but stimulation by tetragastrin or histamine disappeared as a result of this pretreatment. Only tetragastrin-induced activation was completely blocked by the NOS inhibitor. NOS immunoreactivity was limited to surface mucous cells. Mucus-producing cells present in the different sites and layers of the gastric mucosa have distinct mechanisms for regulation of mucin biosynthesis. Gastrin-stimulated mucin biosynthesis mediated by NO is limited to surface mucous cells of rat gastric oxyntic mucosa.

Animals↗

PubMed1998

Biophysical signals underlying myogenic responses in rat interlobular artery.

-To assess cellular mechanisms mediating myogenic responses of interlobular artery (ILA), experiments were performed with the use of isolated perfused hydronephrotic kidneys. ILAs were divided into 3 groups according to their basal diameters: proximal (>60 microm), intermediate (40 to 60 microm), and distal (<40 microm) ILAs. Myogenic responses were obtained by stepwise increase in perfusion pressure. Greater myogenic responsiveness was observed in ILAs with smaller diameters. Diltiazem (10 micromol/L) inhibited myogenic responses of all segments of ILAs. Furthermore, gadolinium (10 micromol/L), a mechanosensitive cation channel blocker, abolished myogenic responses of distal but not proximal ILA. In contrast, 2-nitro-4-carboxyphenyl-N, N-diphenyl-carbamate (200 micromol/L), an inhibitor of phospholipase C, prevented myogenic responses of proximal but not distal ILA. Finally, basal proximal ILA diameters were increased by treatment with 50 nmol/L of staurosporine (P<0.05), and subsequent addition of thapsigargin (1 micromol/L) blocked myogenic contraction of proximal ILAs. Myogenic responses of intermediate ILAs exhibited characteristics between those of distal and proximal ILAs. Our data indicate that underlying mechanisms for myogenic responses differ in distinct segments of ILAs. The present results suggest that mechanosensitive cation channels are involved in myogenic constriction of distal ILAs. Finally, our findings provide evidence that the stimulation of phospholipase C mediates myogenic contraction of proximal ILAs.

Animals↗