Search PubMed⌕ Search

Biomedical subjects

Y Yoshida

Publications and source records attributed to Y Yoshida.

At least 145 records · Page 8Linked to original sources
PubMed2001

Apoptosis of granulosa cells and female infertility in achondroplastic mice expressing mutant fibroblast growth factor receptor 3G374R.

Fibroblast growth factors play an important role in the control of ovarian folliculogenesis, but the complete repertoire of ovarian receptors which can transduce the fibroblast growth factor signals and their precise localization in the ovary have not yet been characterized. The most common form of inherited human dwarfism results from a point mutation in the transmembrane region of fibroblast growth factor receptor 3. A mouse model for achondroplasia was generated by introducing the human mutation (glycine 380-arginine) into the mouse fibroblast growth factor receptor 3 (G374R) by a "knock-in" approach using gene targeting leading to a constitutively active receptor. This resulted in the development of dwarf mice that share many features with human achondroplasia. Here we report that female (fibroblast growth factor receptor 3 G374R) dwarf mice become infertile. While no significant changes were observed in the anatomical and histological appearance of ovaries of 3-wk-old dwarf mice, a dramatic difference was observed in ovaries of 3-month-old mice. The normal ovary consists mainly of healthy corpora lutea and follicles at different stages of development, whereas the ovaries of the dwarf mice remain small and contain mainly follicles with a progressive apoptosis in the granulosa cells, and no corpora lutea could be observed. The levels of LH, FSH, and progesterone were lower by 72.3%, 38.0%, and 40.0%, respectively, in the blood of the dwarf mice compared with normal mice, and the total bioactivity of pituitary FSH and LH was lower by 65.6% and 79.6%, respectively, in the dwarf mice compared with normal mice. However treatment with PMSG and human CG of the dwarf mice led to rapid follicular development and formation of corpora lutea. Interestingly, the expression of the tumor suppressor gene p53 was increased dramatically in ovaries of the dwarf mice. The presence of the fibroblast growth factor receptor 3 cellular receptors in both normal and dwarf animals was demonstrated by Western blot and immunostaining. However, the distribution of the fibroblast growth factor receptors in the two strains shows significant differences. In the normal ovaries fibroblast growth factor receptor 3 was homogeneously distributed on the cell membrane of the granulosa cells and was absent in theca as well as corpora lutea cells, whereas in dwarf mice ovaries it was highly clustered on granulosa cells and very often appears in endocytic vesicles. Aged oocytes were more frequently observed in preantral follicles of ovaries of the dwarf mice. Nevertheless, oocytes isolated from antral follicles resume their meiotic division at a high percentage, similar to oocytes obtained from normal ovaries. The results imply fibroblast growth factor receptor 3 involvement in the control of follicular development through regulation of granulosa cell growth and differentiation, and that unovulation in the dwarf mice could be overcome in part by administration of exogenous gonadotropins. Moreover, it is suggested that the infertile phenotype is partially due to defects in the pituitary-gonadal axis.

Achondroplasia↗
PubMed2001

Effect of instillation method on the absorption of phenolsulphonphthalein as a model drug from the liver and small intestinal serosal surface in rats.

We have examined the effect of the instillation method on the absorption of a drug from the liver and the small intestinal serosal surface in rats. We performed continuous microinstillation via an infusion pump and bolus instillation via a syringe, using phenolsulphonphthalein (phenol red) as the model drug. After continuous microinstillation of phenolsulphonphthalein 2.35 mg in 235 microL for 5 min on the liver and small intestinal serosal surface in rats, the AUC (area under the curve) of the plasma concentration profile up to 60 min was significantly higher compared with bolus instillation. A similar trend was observed after continuous microinstillation of phenolsulphonphthalein 2.35 mg in 117.5 microL for 2.5 min. The calculated absorption rate constants (Ka) after continuous microinstillation of phenolsulphonphthalein based on a two-compartment model with first-order absorption were higher than those after bolus instillation on the liver and small intestinal serosal surface at either instillation concentration. Moreover, Ka was increased after continuous microinstillation of 2.35 mg in 117.5 microL at either instillation site. Instillation of phenolsulphonphthalein on the liver surface resulted in a 1.2- to 2.3-fold higher Ka compared with the small intestinal serosal surface. This tendency was marked after continuous microinstillation of 2.35 mg in 117.5 microL. In conclusion, absorption could be enhanced by instilling a small amount of drug solution on the liver surface gradually and continuously, suggesting a promising approach for instillation site-selective drug delivery in the peritoneal cavity.

Algorithms↗
PubMed2001

Conserved Wat1/Pop3 WD-repeat protein of fission yeast secures genome stability through microtubule integrity and may be involved in mRNA maturation.

Accurate chromosome segregation is dependent upon the integrity of mitotic spindles, which pull each pair of sister chromatids towards opposite poles. In this study, we have characterised fission yeast pop3-5235, a diploidising mutant that is impaired in genome stability. Pop3 is the same as Wat1, a conserved protein containing 7 WD repeats. Pop3/Wat1 has also been isolated from a two-hybrid screen as a binding partner to Prp2, the large subunit of the essential splicing factor U2AF. In wat1 mutants, the cellular amount of alpha-tubulin is decreased to very low levels, which results in compromised microtubules and spindles, consequently leading to unequal chromosome separation. Further analysis shows that, in spite of the binding between Wat1 and Prp2, Wat1 may not be involved directly in splicing reactions per se. Instead, we find that Wat1 is required for the maintenance of alpha-tubulin mRNA levels; moreover, transcript levels of genes other than the alpha-tubulin gene are also equally decreased in this mutant. Wild-type Wat1, but not the mutant protein, forms a large complex in the cell with several other proteins, suggesting that Wat1 functions as a structural linker in the complex. The results suggest that Wat1 plays a role in mRNA maturation as a coupling protein between splicing and synthesis and/or stabilisation.

Amino Acid Motifs↗
PubMed2001

Structure-activity relationships of N-(3,5-dimethoxy-4-n-octyloxycinnamoyl)-N'-(3,4-dimethylphenyl)piperazine and analogues as inhibitors of acyl-CoA: cholesterol O-acyltransferase.

A novel series of acyl-CoA: cholesterol O-acyltransferase (ACAT) inhibitors were synthesized from a lead compound, 1-(4-hydroxy-3-methoxyphenyl)-7-phenylhept-1-en-3-one (1, Yakuchinone B) through a modification of three regions (A, B, C) in the molecule. In this study, the compounds prepared were tested for in vitro inhibitory activity on microsomal ACAT from the liver of rats and for in vivo hypocholesterolemic activity in rats given a high cholesterol diet. N-(3,5-Dimethoxy-4-n-octyloxycinnamoyl)-N'-(3,4-dimethylphenyl)piperazine (45), which belongs to the amide compounds, has finally been discovered. Compound 45 inhibited rat hepatic ACAT in a more striking manner than CI-976, an amide compound ACAT inhibitor, and it exhibited a high level of hypocholesterolemic activity in vivo. Since 45 strongly inhibited both microsomal ACAT prepared from HepG2 (a cell line derived from human hepatocarcinoma) and Caco2 (a cell line derived from human colon adenocarcinoma), there is speculation that 45 might have the ability to inhibit ACAT in both the human intestine and liver independent of the difference in the distribution of ACAT isozymes. On the other hand, 45 did not induce adrenotoxicity in subacute toxicity studies in rats. These results suggest that it has promise for development as a new therapeutic agent for hypercholesterolemia and atherosclerosis.

Animals↗
PubMed2001

Activation-recovery intervals of 12-lead electrocardiograms before and after catheter ablation in patients with Wolff-Parkinson-White syndrome.

Preexcitation in Wolff-Parkinson-White syndrome (WPW) has been reported to induce long-lasting changes in ventricular recovery properties. However, there has not been a report concerning changes in the activation-recovery interval (ARI) in 12-lead ECGs before and after catheter ablation (CA) in patients with WPW syndrome. The present study compared changes in ARIs from 12-lead ECGs with those from body surface unipolar leads before and after CA to examine whether ARIs from limb leads of 12-lead ECGs provide useful information on changes in recovery properties in addition to the ARIs from precordial leads. The study population consisted of 27 manifest WPW patients with a left- (n=18, group A) or right-sided accessory pathway (n=9, group B). ARIs in leads I, II, and III were strongly correlated with those in unipolar leads over the left lateral, left lower, and right lower chest, respectively. ARIs in leads aVR, aVL, and aVF showed a significant correlation with those in unipolar leads over the right upper, left upper, and lower anterior chest, respectively. These correlations were maintained before and after CA. Furthermore, in group A, ARIs in lead V1 tended to increase on day 7 post CA compared with before CA and on day 1. In group B, ARIs in lead III significantly decreased on day 7 compared with before CA and on day 1. These findings suggest that ARIs from the limb leads of 12-lead ECGs may represent those from unipolar leads of a particular area over the body surface, and that ARIs from 12-lead ECGs may provide useful quantitative information on changes in recovery properties before and after CA in patients with manifest WPW syndrome.

Adolescent↗
PubMed2001

Cilnidipine more highly attenuates cold pressor stress-induced platelet activation in hypertension than does amlodipine.

The clinical significance of N-type calcium channel blockade has not been fully examined. We here compared the effects of the N-type calcium channel blockers cilnidipine and amlodipine on the sympathetic nervous system and platelet function in hypertension under resting and stressed conditions. Thirty-two patients with hypertension (58+/-9 years) received cilnidipine or amlodipine for 4 weeks in this crossover study. On day 28 of each treatment, plasma levels of epinephrine (EP), norepinephrine (NEP), and beta-thromboglobulin (BTG), and EC50 of ADP-induced platelet aggregation (ADPE50) were determined at rest and after a cold pressor test. On day 29, the group receiving cilnidipine was switched to amlodipine treatment, and vice versa. At rest, the blood pressure, heart rates, EP, NEP, ADPEC50, and BTG, were similar in both treatments. After the cold pressor test, increases in EP (35+/-17 to 44+/-25 pg/ml; p<0.05) and BTG (40+/-13 to 49+/-22 ng/ml; p<0.01) and a decrease in ADPEC50 (32+/-26 to 27+/-24 micromol; p<0.05) were observed in the amlodipine treatment, but not in the cilnidipine treatment. In addition, the increase in NEP was significantly greater (p<0.05) in the amlodipine (276+/-78 to 318+/-87 pg/ml; p<0.01) than in the cilnidipine treatment (273+/-88 to 291+/-100 pg/ml; p<0.05). Cilnidipine more highly attenuates the activation of platelet function in response to cold pressor stress than does amlodipine. Attenuated activation of the sympathetic nervous system via N-type calcium channel blockade may contribute to this phenomenon.

Amlodipine↗
PubMed2001

Rare complication of saccular aneurysm and histological dissection: an autopsy study of 5865 elderly cases.

The purpose of this study was to examine complicated lesions of saccular aneurysm and dissection. We investigated the ascending aortae in 5865 consecutive elderly autopsy cases, and 5 cases (0.085%) of aortic saccular aneurysms associated with dissection at the edges were selected. Their edges characteristically protruded like a shelf, which histologically consisted of an inner part of the dissected media. All patients were female and their mean age was 76.8 (67-89) years. The aneurysmal walls at the center showed severe fragmentation and disappearance of the elastic lamellae of the remaining outer media. Thus, partial sections of these lesions were not sufficient but cross-sections of the whole diseased regions including the edges were essential for diagnosis. One patient had 3 saccular aneurysms and an adjacent shallow depression, which we called "healed microscopic dissection". Histologically, it showed disappearance of the inner media and was replaced by fibrosis in continuation from the intima. This lesion showed no findings of intramural hemorrhage or thrombus, and thus it will differ from organized thrombi in the dissected false lumen. Another patient presented had an aneurysmal rupture which resulted in cardiac tamponade. This case implies the need for surgical treatment of this entity.

Aged↗
PubMed2001

Immunolocalization of aquaporin-8 in rat digestive organs and testis.

Expression of aquaporin-8 mRNA has previously been shown in hepatocytes, pancreatic acinar cells, colon epithelial cells and seminiferous tubules of the testis in the rat by in situ hybridization technique. However, immunolocalization of this water channel has not yet been demonstrated. In the present study, the localization of immunoreactive aquaporin-8 and expression of the mRNA were examined in rat organs (cerebrum, cerebellum, eye, salivary gland, heart, lung, liver, pancreas, esophagus, stomach, jejunum, ileum, colon, testis, ovary, kidney, spleen and lymphnode) by immunohistochemistry using an antibody against aquaporin-8 and ribonuclease protection assay. Aquaporin-8 was distinctly immunolocalized on the apical membranes of pancreatic acinar cells and mucosal epithelium of the colon and jejunum. In the liver, the bile canalicular membrane of hepatocytes was immunostained. In the testis, immunoreactive aquaporin-8 was demonstrated on the luminal side of the seminiferous tubules. At high magnification, the peroxidase reaction products appeared on the ramified cytoplasmic membrane of Sertoli cells surrounding the residual bodies or spermatogenic cells. Specificity of the antibody was verified by Western blot analysis showing a minor approximately 28 kDa band (deduced deglycosylated form of aquaporin-8) and a major approximately 30 kDa band (glycosylated form) in these organs. The intensity of aquaporin-8 immunoreactivity was approximately comparable to that of aquaporin-8 mRNA expression in the liver, pancreas, colon, jejunum and testis. The aquaporin-8 mRNA expression in the hepatocytes was presumed to be closely associated with the structure of bile canaliculi since the message was detected in hepatocytes immediately after isolation from the liver but not in cells following cultivation for three days. The localization of immunoreactive aquaporin-8 indicated functions for this water channel in the secretion of bile and pancreatic juice, and the secretion or absorption of water in the colon and jejunum, and the maturation or liberation of spermatogenic cells in the testis.

Animals↗
PubMed2001

Expression and immunolocalization of AQP6 in intercalated cells of the rat kidney collecting duct.

The expression and localization of AQP6 were examined in rat kidneys. In the kidney compartments, the expression was more intense in the outer medulla than in the cortex or inner medulla, and was negative in the glomerulus. During development, the AQP6 mRNA expression in the kidney was not detected in the fetus, but was recognized at birth, increased gradually by 4 weeks of age, and was unchanged thereafter. In situ hybridization demonstrated significant signals for AQP6 mRNA along the outer and inner medullary collecting ducts. Since the localization of the AQP6 mRNA-expressing cells was comparable to that of immunoreactive H+ ATPase-bearing cells in the collecting duct, they were identified as intercalated cells. No AQP6 mRNA signals were recognizable in other cells in the kidneys, including glomerular cells. No glomerular expression of AQP6 mRNA was confirmed by RT-PCR using total RNA extracted from the glomeruli. Immunohistochemistry using an antibody raised against recombinant rat AQP6 protein could localize the immunoreactivity in a population of collecting duct cells. Serial section observations indicated that the AQP6-immunoreactive cells corresponded to H+ ATPase bearing intercalated cells.

Animals↗
PubMed2001

Effects of zinc deficiency/zinc supplementation on ammonia metabolism in patients with decompensated liver cirrhosis.

Hepatic encephalopathy is one of the major complications in decompensated liver cirrhosis. The current study was conducted to clarify the mechanisms of zinc deficiency in liver cirrhosis and its involvement in hepatic encephalopathy via ammonia metabolism. Ten patients each with compensated or decompensated liver cirrhosis and 11 healthy volunteers were enrolled in the study. Serum zinc levels and its daily urinary excretion were measured, an oral zinc-tolerance test was performed to examine zinc malabsorption, and the effects of diuretics on zinc excretion and of zinc supplementation on ammonia metabolism in the skeletal muscle were studied. The mean serum zinc levels in patients with decompensated liver cirrhosis were found to be significantly lower than the levels in controls and patients with compensated liver cirrhosis. The serum zinc levels were inversely correlated with blood ammonia in the fasting state. In the oral zinc-tolerance test, the percent increase in serum zinc levels 120 and 180 min after ingestion was less in cirrhotic patients than in controls. A diuretic administration resulted in a significant reduction in serum zinc levels. An increased uptake of ammonia by and an increased release of glutamine from leg skeletal muscle after oral supplementation of zinc sulfate were evident. Taken together, zinc deficiency in decompensated cirrhotic patients appears to be due to low absorption and to high urinary excretion, for which excessive diuretic administration is, in part, responsible, and zinc supplementation might play an important role in the prevention of hepatic encephalopathy by activating glutamine synthetase.

Ammonia↗
PubMed2001

Epidemiological study on improving the QOL and oral conditions of the aged--Part 1: The relationship between the status of tooth preservation and QOL.

In part 1 of this epidemiological study, a survey was conducted for all senior citizens aged 70 and over who resided in a mountainous village in the mid-section of Hyogo Prefecture. It focused on the relationship among the number of existing teeth, life environment, health status, and activities of daily living; and the correlation between oral status and QOL was analyzed. The daily activities of individuals were compared between those having one or more teeth and others who were totally edentulous. Subsequently, it was found that for both males and females, the odds ratio was significantly high for the dentulous individuals, in comparison with edentulous individuals, to exhibit a behavior indicative of a better QOL (such as "opportunity for conversation with family members or others)", "regular physical activities", and "attend meetings or group outings"). The result of this survey indicates that the presence of teeth is very closely related to one's daily activities. It was concluded that preventing tooth loss is vital for maintaining the masticatory function; so to prevent tooth loss, periodontal disease must be averted.

Aged↗
PubMed2001

Epidemiological study on improving the QOL and oral conditions of the aged--Part 2: Relationship between tooth loss and lifestyle factors for adults men.

Oral health in early- and mid-adulthood is essential for the improvement of one's QOL, this study was investigated to include an epidemiological analysis of the relationship between tooth loss and life style, such as smoking, regular exercise, and the food habits of approximately 2,000 employees. Compared with the group with mild or no periodontal disease (CPI of 0, 1, or 2), the frequency of tooth loss in the group with advanced periodontal disease (CPI of 4) was 2.00 times (odds ratio, 2.00; 95% confidence limit, 1.37 to 2.93). The probability of tooth loss showed statistical significance in relation to smoking, alcohol drinking, and frequency of meals. Compared with non-smokers, the probability that current smokers will lose teeth is 1.53 times greater (odds ratio, 1.53; 95% confidence limit, 1.20 to 1.96). It was concluded that periodontal disease and smoking must be averted for preventing tooth loss.

Adult↗
PubMed2001

Pheochromocytoma of the urinary bladder revealed with cerebral hemorrhage.

The case was a 51-year-old man, who has been undergoing treatment with oral medication for hypertension for three years. The patient was admitted to the author's clinic for hemorrhage in the left putamen. He was diagnosed as having primary pheochromocytoma of the bladder from such symptoms as paroxysmal blood pressure elevation after urination, mild increase in catecholamine levels before and after urination, and from the results of 131I-MIBG scintigraphy, and cystoscopy, and underwent excision of the bladder tumor. Upon endocrinological examination, only mild increases in catecholamine levels were found. Therefore, constant monitoring of blood pressure and 131I-MIBG scintigraphy were useful for a definitive diagnose.

Catecholamines↗
PubMed2001

Importance of CCK-A receptor for gallbladder contraction and pancreatic secretion: a study in CCK-A receptor knockout mice.

Bile and pancreatic secretions were determined in a CCK-A receptor deficient mouse mutant generated by gene targeting in embryonic stem cells. The targeting vector contained lacZ and neo insertions in exon 2. Under the urethane anesthesia, the common bile duct was cannulated, and the mixture of bile-pancreatic juice was collected every 30 min. After the 1 h basal secretion, CCK-8 (0.5 and 1.0 nmol/kg), acetylcholine (500 nmol/kg), and neuromedin C (1.0 micromol/kg) were injected subcutaneously, and the secretions were collected following 1 h. Amylase and bile acid outputs were determined as parameters of pancreatic secretion and gallbladder contraction, respectively. In some CCK-A receptor (+/-) animals, LacZ staining was performed. CCK-8 significantly increased amylase and bile acid outputs in CCK-A receptor (+/+) and (+/-) mice, whereas no response was observed in (-/-) mice. Neuromedin C and acetylcholine increased amylase secretion in CCK-A receptor (-/-) mice similar to (+/-) and (+/+) mice. The same doses of neuromedin C and acetylcholine could not increase bile acid secretion. The gallbladder smooth muscles, pancreatic acinar cells, duct cells, and islets were stained by LacZ. CCK and CCK-A receptor are important for pancreatic secretion and gallbladder contraction. Neuromedin C and acetylcholine may compensate pancreatic function, but not gallbladder contraction.

Acetylcholine↗
PubMed2001

An unusual staining of the tooth roots: a case report with histological and micro-analytical studies.

The discoloration of tooth roots is rare. We report here a 22-year-old Japanese woman with blackish-brown staining of the roots of the upper and lower third molars. Staining was found in the dentin and cementum. Electron probe X-ray microanalysis showed no significant difference in the composing elements between the stained tooth root and control tooth. Fluorescent bands coincided with staining in the dentin of the root and cementum along the incremental lines under confocal laser-scanning microscope.

Adult↗
PubMed2001

Histological and analytical studies of a tooth in a patient with cleidocranial dysostosis.

A histopathological and analytical study of a permanent tooth from a patient with cleidocranial dysostosis (CCD) was performed. The patient was a 47-year-old woman, who had 10 erupted permanent teeth and 2 partially erupted and 19 completely impacted teeth, including supernumerary teeth. The erupted right upper premolar was extracted and observed using a light microscope and an electron probe X-ray microanalyzer (EPMA). Findings showed enamel hypoplasia, predominantly irregular globular dentin and Tomes' granular layer, and a complete lack of cellular cementum in the ground section. The incremental von Ebner and counter Owen lines were obscure. Comparative quantitative analysis using the EPMA showed that the quantities of calcium and phosphate were lower in the enamel and dentin than those of the control sample.

Bicuspid↗
PubMed2001

Suppressive effects of bifidobacteria on lipid peroxidation in the colonic mucosa of iron-overloaded mice.

The antioxidative effects of live bifidobacteria on lipid peroxidation in the colonic mucosa were investigated. Bifidobacterium bifidum strain Yakult, which has been used for production of fermented milk, most effectively inhibited lipid peroxidation catalyzed by ferrous iron in liposomes among 10 species of bifidobacteria from human intestinal flora. Oral administration of B. bifidum strain Yakult for 2 wk significantly decreased the level of lipid peroxide (thiobarbituric acid reactive substance) in the colonic mucosa of iron-overload mice (Fe 0.07% in diet). The iron concentrations in plasma and cecum contents were not affected by administration of B. bifidum strain Yakult. Bifidobacterium bifidum strain Yakult had no chelating or incorporating activity for ferrous iron in vitro. Therefore, the antioxidative effect of B. bifidum strain Yakult in the colonic mucosa was not thought to be based on the removal of ferrous iron from the reaction system of lipid peroxidation. These results suggested that B. bifidum strain Yakult protected the colonic mucosa from oxidative injury without inhibiting iron absorption.

Animals↗