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Biomedical subjects

K Ishihara

Publications and source records attributed to K Ishihara.

At least 235 records · Page 13Linked to original sources

Serum and antral gastrin levels in fed and fasted rats: relation to aging.

The effect of short fasting for up to 24 h on serum and antral gastrin concentrations and G cell ultrastructure has been examined in the young rat compared with the middle-aged rat. The serum gastrin levels at 24-h fasting were markedly reduced in both young and middle-aged rats. There was also a significant decrease in antral gastrin concentrations after 24 h of fasting in the middle-aged rats. By contrast, the antral gastrin concentrations in the young rats increased progressively and significantly with fasting for up to 24 h. These responses were associated with a significant increase in the content of secretory granules of G cell, which was at its greatest by 24 h. The antral gastrin level in the 48-h fasting rats was markedly reduced to a level below that for the prestarvation group. By 48 h of starvation, the amount of secretory granules in G cell was significantly reduced (P < 0.05) compared with the 24-h fasting group. These results indicate that the effects of fasting on the antral gastrin levels in young rats differ from those of the middle-aged and that starvation for up to 24 h caused a significant increase in the antral gastrin content in the young rats' stomach.

Aging↗

Distinct effects of tetragastrin in rat gastroduodenal mucosa on mucin content and mucosal protective action against histamine-induced injury.

We examined the effects of tetragastrin on mucin (mucus glycoprotein) content and mucosal damage in the rat stomach and duodenum. Following an injection of tetragastrin (12, 120, or 400 microg/kg subcutaneously), no macroscopic damage was found to the gastric mucosa but an increase in corpus mucin content was noted, whereas mucosal lesions appeared and the mucin content decreased in the duodenum in a dose-related manner. In the groups with histamine (0.8, 8, or 80 mg/kg intraperitoneally) administration, the extent of mucosal damage and the decrease in mucin content were dose-related in both these regions. For assessment of the effect of tetragastrin on the protective action in gastroduodenal mucosa, changes in mucin content and mucosal damage with histamine (80 mg/kg) -induced injury were examined. Coadministration of tetragastrin prevented the gastric mucosal damage and inhibited the decrease in corpus mucin content. In the duodenum, tetragastrin aggravated the histamine-induced mucosal damage and did not inhibit the reduction of the mucin content. From the present results, the increase in gastric mucins induced by tetragastrin might be related to the protective effect of gastric mucosa against injury. Tetragastrin did not protect the duodenal mucosa, and histamine-induced injury occurring in this region would be aggravated by the increase in HCl secretion and the decrease in mucin content induced by tetragastrin.

Animals↗

Induction of metamorphosis in the sand dollar Peronella japonica by thyroid hormones.

The larva of the sand dollar Peronella japonica lacks a mouth and gut, and undergoes metamorphosis into a juvenile sand dollar without feeding. In the present study, it was found that thyroid hormones accelerate the metamorphosis of P. japonica larvae. The contents of thyroid hormones in larvae increased gradually during development. Thiourea and potassium perchlorate, inhibitors of thyroid hormone synthesis, delayed larval metamorphosis and simultaneously repressed an increase in the content of thyroxine in the larval body. These results suggest that the P. japonica larva has a system for synthesis of thyroid hormones that act as factors for inducing metamorphosis.

Animals↗

Detection rate of the cervical gland area during pregnancy by transvaginal sonography in the assessment of cervical maturation.

OBJECTIVES: To detect the cervical gland area during normal pregnancy, and to determine its detection rate and relationship with cervical maturation. DESIGN: This was a mixed longitudinal and cross-sectional sonographic study involving a total of 514 transvaginal scans performed for detection of cervical gland area and measurement of cervical length in 260 normal singleton pregnancies at 16-41 weeks of gestation. The conventional cervical maturation index was measured simultaneously by digital examination. RESULTS: The detection rate of cervical gland area remained practically constant until the 31st week of pregnancy, but significantly decreased thereafter. Highly significant correlations were noted between the detection rate of cervical gland area and cervical length, cervical gland area and cervical maturation index, and cervical length and cervical maturation index. CONCLUSIONS: This study showed for the first time that cervical gland area can be detected sonographically and that its absence might be a predictor of preterm labor.

Adolescent↗

Enhancement of GABA-mediated inhibition of rat medial vestibular nucleus neurons by the neurosteroid 20-hydroxyecdysone.

In vivo electrophysiological and patch-clamp studies were performed to determine whether 20-hydroxyecdysone (20-HE), a neurosteroid, influenced neuronal activities of the medial vestibular nucleus (MVN) using chloral hydrate-anesthetized rats and dissociated MVN neurons, respectively. Single neuronal activities of MVN were extracellularly recorded with a glass-insulated silver wire microelectrode attached along a seven-barreled micropipette. Each micropipette was filled with 20-HE, glutamate, bicuculline or 2 M NaCl. These chemicals were applied microiontophoretically to the immediate vicinity of the target neurons. Microiontophoretically applied 20-HE (20-80 nA) dose-dependently decreased rotation-induced firings of both type I and II neurons, which were identified according to their responses to horizontal sinusoidal rotations. Microiontophoretically applied bicuculline, a GABAA receptor antagonist, inhibited 20-HE-induced decreases in neuronal firing of MVN. These findings suggest that 20-HE potentiates the action of GABA, probably by acting directly on the GABAA receptor of MVN neurons. In addition, microiontophoretically applied 20-HE decreased firings induced by glutamate in both type I and II neurons. This decrease by 20-HE was also antagonized with bicuculline. Furthermore, the effects of 20-HE on GABA-induced currents in acutely dissociated MVN neurons were investigated using the whole-cell patch-clamp technique. Under voltage-clamp conditions, GABA (10 microM)-induced currents were potentiated in the presence of 20-HE (100 microM). These findings suggest that 20-HE inhibits MVN neurons by acting on the modulatory site on GABA receptor-ion channel complexes to potentiate GABA inhibition.

Animals↗

Swimming capacity of mice is increased by oral administration of a nonpungent capsaicin analog, stearoyl vanillylamide.

Intravenous injection of stearoyl vanillylamide (C18-VA), a nonpungent capsaicin (CAP) analog, enhances adrenaline secretion significantly and as effectively as CAP in rats. Because swimming capacity was enhanced by CAP in mice due to CAP-induced adrenal catecholamine secretion, we investigated the effects of oral administration of C18-VA on swimming capacity using an adjustable-current water pool. Male Std ddY 6-wk-old mice were fed a commercial diet for this study and one group was orally administered C18-VA via a stomach tube. Treated mice were able to swim longer before exhaustion than the control mice (62.9 +/- 5.6 vs. 49.6 +/- 7. 0 min, P < 0.05). The swimming capacity of two groups administered C18-VA (0.02 and 0.033 mmol/kg) was significantly greater than that of those administered vehicle alone, (P < 0.05). Substance P concentration in cerebrospinal fluid, which is involved in pain transmission and is the first direct measure of pungency, was not affected by C18-VA administration. In an experiment examining the effects of C18-VA on serum adrenaline concentration, adrenaline was significantly greater in C18-VA treated mice than in controls at 2-h post-dose (C18-VA group, 26.09 +/- 2.82; control group 13.29 +/- 0. 96 microg/L, P < 0.01). In a separate study free fatty acids in serum were elevated in treated mice at 2-h post-dose (P < 0.01). While serum glucose concentration was not affected. These results suggest that C18-VA increased swimming capacity of mice via adrenaline release, independent of pungency. In addition, the present study suggests the usefulness of its application to humans.

Animals↗

Autoantibodies against a 210 kDa glycoprotein of the nuclear pore complex as a prognostic marker in patients with primary biliary cirrhosis.

It has been reported that the presence of anti-nuclear antibody against a 210 kDa glycoprotein of nuclear pore complex (anti-gp210) is highly specific for primary biliary cirrhosis (PBC). The aim of the present study was to investigate the significance of anti-gp210, especially as a prognostic marker. The presence of anti-gp210 was ascertained in 113 patients with PBC and 162 controls by indirect immunofluorescence assay using HepG2 cells and immunoblotting analysis using nuclear extracts from HeLa cells. Anti-gp210 was detected in 25 of the 113 (22.1%) patients. None of the 162 controls was positive for anti-gp210. The appearance and titre of anti-gp210 in the patients with PBC did not vary from the time of diagnosis and through their clinical course. Anti-mitochondrial antibodies (AMA), including antibodies against pyruvate dehydrogenase complex, branched chain alpha-ketoacid dehydrogenase complex and alpha-ketoglutarate dehydrogenase complex, were not detected by enzyme-linked immunosorbent assay in five of the 113 (4.4%) patients with PBC. However, anti-gp210 alone was positive in one of these five patients. The difference in prognosis was statistically significant; patients with PBC positive for anti-gp210 died from hepatic failure more frequently than those who were negative (P < 0.01), although there were no statistically significant differences in the frequency of jaundice and the histological stage at the time of diagnosis between the two groups. We suggest that the presence of anti-gp210 is one of the independent prognostic markers able to predict, at the time of diagnosis, a poor outcome in patients with PBC.

Adult↗

A longitudinal study of the development of daytime sleepiness in children.

This study aims to (i) investigate longitudinally developmental changes of diurnal variations of body temperature and sleepiness in preschool and school-age children and (ii) investigate the effect of acute 2 h sleep reduction on daytime sleepiness over a 3 year period. Three subjects were evaluated over three consecutive days: two control days and one 2 h sleep reduction day. A sleep latency test was conducted five times each day at 2 h intervals from 10.00 h, and oral temperature measured every hour. The results showed that (i) daytime sleepiness was high and decreased with increasing age, (ii) an afternoon dip occurred with pubertal development, (iii) effects of sleep loss generally increased daytime sleepiness, in particular at 10.00 h, and (iv) temperature acrophase was delayed with age.

Body Temperature Regulation↗

Systemic mast cell disease with splenic infarction: a case report.

An autopsy case of systemic mast cell disease (SMCD) without primary skin lesions in a 57-year-old Japanese male is described. Initially the patient was suspected of having liver cirrhosis or malignant lymphoma because of hepatomegaly and lymph node enlargement on admission. However, a lymph node biopsy and bone marrow aspiration conducted on his third admission indicated a SMCD because of the existence of metachromatic cell aggregates stained with toluidine blue. At autopsy, the diagnosis was confirmed because the proliferating cells were histochemically proven to be mast cells by naphthol AS.D chloroacetate esterase, Giemsa and alcian blue, in addition to toluidine blue staining. The intra-abdominal and retroperitoneal lymph nodes were replaced by mast cell aggregates, which caused the splenic infarction and bilateral hydronephrosis, with infiltration of mast cells into the spleen and kidneys also being apparent. Mast cell infiltration was similarly found in the bone marrow, liver, ileum and ascending colon. Immunohistochemically, the mast cells were positive for antibodies of alpha 1-antichymotrypsin, CD45 (LCA), CD43 (MT-1), CD45R (MB-1) and the oncoprotein c-kit. Electron microscopic examination using formalin-fixed tissue gave supportive evidence of a mast cell origin for the lesions.

Fatal Outcome↗

Increased use of inhaled corticosteroids and reduced hospitalizations in adult asthmatics: 11 years' experience in a Japanese hospital.

Until recently, inhaled corticosteroids have not been recognized as a first-line drug mainly because of the traditional polypharmaceutical approach to asthma in Japan. To examine the trend more precisely following the introduction of inhaled corticosteroids, we retrospectively analysed the relation between the number of prescriptions for anti-asthma drugs including inhaled corticosteroids and the number of hospitalizations due to asthma exacerbation, near fatal episodes and deaths from asthma for a period of 11 years from 1986 to 1996 at Kobe City General Hospital (KCGH). A marked decline in these actual indices in patients attending KCGH, which shows the improvement in asthma control, started coincidentally with the increased use of inhaled corticosteroid, which was followed by both a discontinuation of the trend for increased use of inhaled beta-agonists and the decreased use of oral anti-asthma agents. There was no significant difference in the mean duration of hospital stays between 1988 and 1996. Although the intensification of patient education is likely to play an important role in enhancing the protective effect of inhaled corticosteroids, we highly suspect that the major contributory factor in the great decline in hospitalizations is the increased use of inhaled corticosteroids.

Administration, Inhalation↗

Inhibition of Helicobacter pylori sialic acid-specific haemagglutination by human gastrointestinal mucins and milk glycoproteins.

Helicobacter pylori, a human gastric pathogen causing chronic gastritis and duodenal ulcer disease, has been found in large amounts in gastric mucous gel layer. Mucin preparations, separated from human gastric juices and isolated from different colon regions, were examined for their ability to inhibit haemagglutination of H. pylori with the emphasis on evaluating the role of sialic acid-dependent haemagglutinins of the bacteria in colonisation of the stomach. The mucins showed high inhibitory activity for H. pylori, which was significantly decreased after the removal of sialic acids from the mucins. The inhibitory potencies using high molecular mass mucin-like components from bovine milk were comparable with those obtained for gastric mucins, suggesting their possible role in the prevention of H. pylori infection.

Animals↗

Adaptive changes in membrane lipids of barophilic bacteria in response to changes in growth pressure.

The lipid compositions of barophilic bacterial strains which contained docosahexaenoic acid (DHA [22:6n-3]) were examined, and the adaptive changes of these compositions were analyzed in response to growth pressure. In the facultatively barophilic strain 16C1, phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) were major components which had the same fatty acid chains. However, in PE, monounsaturated fatty acids such as hexadecenoic acid were major components, and DHA accounted for only 3.7% of the total fatty acids, while in PG, DHA accounted for 29.6% of the total fatty acids. In response to an increase in growth pressure in strain 16C1, the amounts of saturated fatty acids in PE were reduced, and these decreases were mainly balanced by an increase in unsaturated fatty acids, including DHA. In PG, the decrease in saturated fatty acids was mainly balanced by an increase in DHA. Similar adaptive changes in fatty acid composition were observed in response to growth pressure in obligately barophilic strain 2D2. Furthermore, these adaptive changes in response were also observed in response to low temperature in strain 16C1. These results confirm that the general shift from saturated to unsaturated fatty acids including DHA is one of the adaptive changes in response to increases in pressure and suggest that DHA may play a role in maintaining the proper fluidity of membrane lipids under high pressure.

Journal Article↗

Dentilisin activity affects the organization of the outer sheath of Treponema denticola.

Prolyl-phenylalanine-specific serine protease (dentilisin) is a major extracellular protease produced by Treponema denticola. The gene, prtP, coding for the protease was recently cloned and sequenced (K. Ishihara, T. Miura, H. K. Kuramitsu, and K. Okuda, Infect. Immun. 64:5178-5186, 1996). In order to determine the role of this protease in the physiology and virulence of T. denticola, a dentilisin-deficient mutant, K1, was constructed following electroporation with a prtP-inactivated DNA fragment. No chymotrypsin-like protease activity was detected in the dentilisin-deficient mutant. In addition, the high-molecular-mass oligomeric protein characteristic of the outer sheath of the organism decreased in the mutant. Furthermore, the hydrophobicity of the mutant was decreased, and coaggregation of the mutant with Fusobacterium nucleatum was enhanced compared to that of the wild-type organism. The results obtained with a mouse abscess model system indicated that the virulence of the mutant was attenuated relative to that of the wild-type organism. These results suggest that dentilisin activity plays a major role in the structural organization of the outer sheath of T. denticola. The loss of dentilsin activity and the structural change in the outer sheath affect the pathogenicity of T. denticola.

Animals↗

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↗

Platelet adhesion on the gradient surfaces grafted with phospholipid polymer.

We have synthesized omega-methacryloyloxyalkyl phosphorylcholine (MAPC) polymers as new blood-compatible materials, with attention to the surface structure of the biomembrane and investigated their blood compatibility. The blood compatibility observed on the MAPC polymers is due to their strong affinity to phospholipids. When the blood comes in contact with the MAPC polymer, phospholipids in the plasma preferentially adsorb on the surface, compared with the plasma proteins or cells. The adsorbed phospholipids construct a biomembrane-like structure on the MAPC polymer surface. The MAPC polymers then have an excellent blood compatibility. In this study, we prepared a gradient poly(MAPC)-grafted polyethylene (PE) surface using a corona discharge treatment method to clarify the effect of the chemical structure of the MAPC unit on the blood compatibility of the MAPC polymers. The surface composition of MAPC and the hydrophilicity on the poly(MAPC)-grafted PE surface were determined by X-ray photoelectron spectroscopic (XPS) analysis and contact angle measurement with water, respectively. The phosphorus/carbon (P/C) ratio determined by the XPS analysis increased, but the water contact angle decreased with increasing corona irradiation energy. These results indicated that the surface density of the MAPC unit was increased. More than 2.5 cm from the starting point of the corona irradiation, the P/C ratio and water contact angle of the surface achieved a constant level. Thus, the surface was completely covered with the grafted poly(MAPC) chain. The effect of the methylene chain length of the MAPC unit on surface properties was also observed. The phospholipid polar group of the MAPC unit was effectively exposed on the surface as the chain length became longer. Moreover, the hydrophobicity of the surface was increased with the increase in the methylene chain length of the MAPC unit. The number of platelets adhering to the poly(MAPC)-grafted PE surface was reduced from the same point where the P/C ratio became constant.

Animals↗

Histochemical reactivity of normal, metaplastic, and neoplastic tissues to alpha-linked N-acetylglucosamine residue-specific monoclonal antibody HIK1083.

Monoclonal antibody (MAb) HIK1083, which is obtained by immunizing mice with a preparation of rat gastric mucins, has been shown to bind specifically to alpha-linked N-acetylglucosamine (alpha-GlcNAc). We investigated the specificity of MAb HIK1083 by immunostaining normal human organs, mucinous metaplasia of human pancreas, adenocarcinomas of human stomach, pancreas, and colon, and normal rat organs. The specificity was investigated by making comparisons with (a) a stain that labels Class III concanavalin A (ConA)-reactive mucin (Class III mucin), i.e., paradoxical ConA (PCS), and (b) staining with horseradish peroxidase (HRP)-conjugated Griffonia simplicifolia agglutinin II (GSA-II). In normal human and rat organs and in mucinous metaplasia of human pancreas, immunostaining with MAb HIK1083 and PCS showed similar specificities for mucins in glandular mucous cells. In adenocarcinoma of stomach and pancreas, GSA-II showed the most widespread positivity, PCS showed the least, and MAb HIK1083 showed a reactivity between those two extremes. Colon adenocarcinomas were labeled only with GSA-II. These results demonstrate that MAb HIK1083 could be a useful screening tool for Class III mucin in normal, metaplastic, and carcinoma tissues, and that the alpha-GlcNAc residue is one of the specific sugar residues found in Class III mucin.

Acetylglucosamine↗

Reduced protein adsorption on novel phospholipid polymers.

We have synthesized phospholipid polymers containing 2-methacryloyloxyethyl phosphorylcholine (MPC) units as novel blood compatible polymers and have evaluated their interactions with blood components. It was found that in the absence of anticoagulants, blood clotting was delayed and blood cell adhesion and activation were effectively prevented on the MPC copolymer surface. A little amount of protein adsorbed on the MPC copolymer from human plasma was compared with conventional polymers, and the amount was reduced with increasing MPC unit fraction. To clarify the reason for the little protein adsorption on the MPC copolymer, the water structure in the hydrated polymer was examined with attention to the free water fraction. Hydration of the polymers occurred when they were immersed in water. The thermal analysis of these hydrated polymers revealed that the free water fractions in the poly(MPC-co-n-butyl methacrylate (BMA)) and poly(MPC-co-n-dodecyl methacrylate) were significantly larger than those in the poly(2-hydroxyethyl methacrylate(HEMA)). The conformation of proteins adsorbed on poly(HEMA) changed considerably but that on poly(MPC-co-BMA) was almost the same as the native state. We concluded from these results that the proteins are hardly adsorbed and do not change their original conformation on the polymer surfaces which possess a high free water fraction such as phospholipid polymers.

Adsorption↗

Aortic root replacement for Takayasu arteritis associated with ulcerative colitis and ankylosing spondylitis--report of a case.

A 26-year-old man was admitted for treatment of congestive heart failure resulting from aortic regurgitation. The patient had been on medical treatment for ulcerative colitis (UC) since he was 14 years old and for ankylosing spondylitis (AS) since he was 20 years old. On admission, gradients of blood pressure among the extremities were observed. Echocardiography revealed marked dilation of the left ventricle (LV), hypokinetic wall motion of the LV, slightly prolapsed aortic cusps with annular dilatation, and severe aortic regurgitation. Computed tomographic scans demonstrated an aneurysmal dilation of the ascending aorta and thickening of the descending and abdominal aortic wall. Digital subtraction angiography demonstrated an aneurysmal dilation of the ascending aorta; however, there was no clear evidence of steno-occlusive lesions in the brachiocephalic vessels. Blood studies showed positive inflammatory signs and negative rheumatoid factor. HLA typing showed A2, 24(9), B27, 67, Cw1, 7, and DR1, 2. Based on these data, the diagnosis of Takayasu arteritis associated with UC and AS was made. Aortic root replacement was performed. Steroid therapy was restarted immediately after surgery. Histologic studies of the aortic wall showed findings compatible with Takayasu arteritis. The combination of these rare diseases suggests that they have a common pathophysiologic background.

Adult↗