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Biomedical subjects

K Shibata

Publications and source records attributed to K Shibata.

At least 145 records · Page 8Linked to original sources

Potentiation of the hypotensive effect of adrenomedullin in pregnant rats.

The hypotensive effect of adrenomedullin, a potent vasodilator peptide, was examined in conscious pregnant (6, 13 and 20 days of pregnancy) and non-pregnant rats. The intravenous administration of adrenomedullin (0.01-3.0 nmol/kg) produced a dose-dependent depressor response in pregnant and non-pregnant rats. At low doses (0.01-0.1 nmol/kg), the maximum decrease in blood pressure was significantly higher in pregnant rats (20 days pregnant) than in non-pregnant rats. At high doses, no significant difference was observed between the two groups. Furthermore, the administration of adrenomedullin did not significantly affect the basal mean blood pressure (MBP) at any dose when compared to the non-pregnant group at 6 and 13 days of pregnancy. In the ovariectomized rats, the depressor responses in 17beta-estradiol-treated, progesterone-treated and 17beta-estradiol+progesterone-treated rats were not significantly different from that in the control rats, suggesting that the augmented effect on the depressor response to adrenomedullin in pregnant rats may not be due to hormonal changes during pregnancy. The adrenomedullin receptor mRNA level of the descending thoracic aorta was significantly higher in the late-pregnancy rats (20 days of pregnancy). However, the levels did not show any difference between the early-pregnant rats (6 and 13 days of pregnancy) and the non-pregnant rats. These findings suggested that the changes in the depressor response to adrenomedullin which occur at term in pregnant rats may be mediated by changes of adrenomedullin receptor gene expression rather than by sex hormones.

Adrenomedullin↗

Origin of the Universal Correlation between the Flare Temperature and the Emission Measure for Solar and Stellar Flares.

We present a theory to explain the observed universal correlation between flare temperature T and emission measure EM=n2V for solar and stellar flares (including solar microflares observed by Yohkoh as well as protostellar flares observed by ASCA), where n is the electron density and V is the volume. The theory is based on a magnetic reconnection model with heat conduction and chromospheric evaporation, assuming that the gas pressure of a flare loop is comparable to the magnetic pressure. This theory predicts the relation EM~B-5T17/2, which explains well the observed correlation between EM and T in the range of 6x106 K < T<108 K and 1044<EM<1055 cm-3 from solar microflares to protostellar flares, if the magnetic field strength B of a flare loop is nearly constant for solar and stellar flares.

Journal Article↗

Nickel(0)-Catalyzed Three-Component Connection Reaction of Dimethylzinc, 1,3-Dienes, and Carbonyl Compounds.

Linear 1:1:1 coupling of dimethylzinc, 1,3-dienes, and carbonyl compounds in this order is facilitated by catalytic amounts of [Ni(acac)(2)] to give (E)-3-hexen-1-ols in good yields under mild conditions [Eq. (a)]. Increasing steric hindrance at the carbonyl group favors formation of the 1:2:1 adduct, and this is the sole product when the carbonyl compound is acetone. acac=acetylacetonate.

Journal Article↗

Determination of N-methyl-D-aspartate in tissues of bivalves by high-performance liquid chromatography.

The natural occurrence of N-methyl-D-aspartate (NMDA) is limited to the foot muscle of Scapharca broughtonii; it is a well known compound for its neuroexitatory activity. This paper describes a high-performance liquid chromatographic (HPLC) method for the determination of NMDA in biological extracts. The method involves removal of neutral and basic substances by anion-exchange chromatography and removal of acidic primary amino acids by treatment with o-phthalaldehyde before derivatization with (+)-1-(9-fluorenyl)ethyl chloroformate, followed by HPLC with isocratic elution with a selected mobile phase that separates the two diastereomers formed. The identity of the detected NMDA has been confirmed by a procedure using (-)-1-(9-fluorenyl)ethyl chloroformate as a derivatizing agent. The identification has been further supported by the disappearance of the peak of the NMDA derivative by pretreatment of the sample with D-aspartate oxidase. Application of the method has shown the presence of NMDA in several tissues of S. broughtonii and Scapharca subcrenata.

Animals↗

Adrenomedullin attenuates the hypertension in hypertensive pregnant rats induced by N(G)-nitro-L-arginine methyl ester.

We examined the effect of adrenomedullin on the cardiovascular system of an animal model for preeclampsia. An inhibitor of nitric oxide synthase, N(G)-nitro-L-arginine methyl ester (L-NAME), was infused subcutaneously into rats at a constant rate from day 14 of pregnancy to make an animal model for preeclampsia. Adrenomedullin was continuously infused intravenously at a dose of 3 or 10 pmol/h from day 17 of pregnancy. The basal systolic blood pressure was significantly higher in the L-NAME treated rats than in the control rats. The adrenomedullin administration at day 19 of pregnancy showed a significant decrease in the blood pressure in the L-NAME treated rats than in vehicle rats during infusion. The blood pressure of normal pregnant rats did not significantly decrease by adrenomedullin infusion. The adrenomedullin decreased pup mortality of the L-NAME treated rats. Adrenomedullin attenuated the L-NAME induced hypertension and pup mortality. On the other hand, adrenomedullin administration in both pregnant rats in early gestation (5-11 days of pregnancy) and in non-pregnant rats did not show any significant effect on L-NAME-induced hypertension. The adrenomedullin mRNA level was predominantly expressed at high levels in the ovary, uterus and placenta, but at low levels in other tissues in pregnant rats in late gestation. The adrenomedullin mRNA level of the L-NAME treated rats in placenta decreased more than in the normal pregnant rats in late gestation (P < 0.05). These findings suggest that the adrenomedullin might play an important role in the regulation of the cardiovascular system of the mother and fetoplacental unit in rats.

Adrenomedullin↗

Reduction of post-ischemic lung reperfusion injury by fibrinolytic activity suppression.

BACKGROUND: Although extensive studies on the detailed mechanisms of ischemia-reperfusion injury have been conducted, the implication of the fibrinolytic system has not been known. To determine the role of the fibrinolytic system in ischemia-reperfusion injury, we used tranexamic acid, a synthetic specific plasmin and tissue-type plasminogen activator inhibitor, to suppress fibrinolytic activity in a rabbit lung ischemia-reperfusion model. METHODS: New Zealand White rabbits were randomly divided into two groups: a simple ischemia group and a group injected with tranexamic acid before left hilar occlusion. After 2 hours of warm ischemia, plasma was collected from pulmonary vessels. Fibrin zymography was used to ascertain fibrinolytic activity, and enzyme-linked immunosorbent assay was used to determine soluble thrombomodulin levels as a marker for endothelial cells damage. Changes in left pulmonary function including arterial oxygen tension, peak airway pressure, and pulmonary vascular resistance were recorded during reperfusion after the 2 hours of warm ischemia. RESULTS: Fibrinolytic activity and soluble thrombomodulin levels increased in the vessels of the ischemic lung, indicating endothelial cell injury. The increased fibrinolytic activity and the rise in soluble thrombomodulin were suppressed by the preadministration of tranexamic acid, resulting in remarkably improved pulmonary function during reperfusion. After 2 hours of reperfusion, the wet-to-dry weight ratios and histological studies showed reduced pulmonary edema in the group that had received tranexamic acid. CONCLUSION: These findings suggest that the fibrinolytic system is involved in the onset mechanism of ischemia-reperfusion injury through induced endothelial cell damage and increased vascular permeability.

Animals↗

G-protein gamma 7 is down-regulated in cancers and associated with p 27kip1-induced growth arrest.

We previously identified and cloned human G protein gamma 7 (G-gamma 7) gene, which is down-regulated in pancreatic cancer. We examined G-gamma 7 expression in other gastrointestinal tract cancers. In 24 of 30 patients with gastrointestinal tract cancer, Northern blot assay and immunohistochemical staining revealed significantly lower G-gamma 7 expression in tumors than in normal tissues from the same patients. Semiquantitative reverse transcription PCRs also showed lower G-gamma 7 expression in tumors than in corresponding normal tissues in 69 of 90 patients. To examine the biological role of G-gamma 7 in cancer, the G-gamma 7 cDNA was transfected into a human esophageal carcinoma cell line, KYSE150, that lacks G-gamma 7 expression. G-gamma 7 expression suppressed cell growth and tritiated-thymidine uptake when cells were confluent G-gamma 7 expression also suppressed tumorigenicity in BALB/c nude mice until 3 weeks after transplantation. G-gamma 7 expression increased the Go/G1 population and decreased the S phase population when cells were at high density. We confirmed that this change was associated with p27K1P1 expression. These findings suggest that human G-gamma 7 is associated with p27kip1-induced growth arrest and may be a therapeutic target in cancers.

Animals↗

Antimicrobial triterpenes from Ilex integra and the mechanism of antifungal action.

Antimicrobial triterpenes were isolated from the fruits of Ilex integra. Their structures were elucidated by spectral data and identified as rotundic acid (1), ulsolic acid (2) and peduncloside (3). Triterpene 1 showed significantly broad antimicrobial activity against bacteria, yeast and filamentous fungi. The antifungal activity of 1 was reversed by fatty acids. Cellular constituents leaked from Candida albicans cells incubated with triterpene 1. These results suggest that the antimicrobial activity of triterpenes in I. integra is due to a change of membrane permeability arising from membrane lipid alteration.

Antifungal Agents↗

Expression of immunoglobulin superfamily members on the lymphatic endothelium of inflamed human small intestine.

Previously, lymphatic endothelium of human tissue has been shown to express only platelet-endothelial cell adhesion molecule-1 (PECAM-1). In this study we examined the expression of immunoglobulin superfamily members on the lymphatic endothelium of human small intestine while in the presence of inflammatory cytokines. Lymphatic vessels were identified by using a cocktail of IgGs for desmoplakin I and II while the presence of inflammatory cytokines was determined by the expression of major histocompatibility complex (MHC) class II in the venules. As a result, lymphatic vessels in the tissue with venules expressing MHC class II expressed PECAM-1, intercellular adhesion molecule (ICAM)-1, ICAM-3, and vascular cell adhesion molecule-1 (VCAM-1). The expression of ICAM-3 and VCAM-1 was significantly stronger in lymphatic vessels than in blood vessels. The results suggest that inflamed lymphatic endothelium may allow more lymphocyte subpopulations to adhere to the endothelium than non-inflamed lymphatic endothelium, due to the expression of multiple adhesion molecules playing a role.

Aged↗

Nutritional factors that regulate on the conversion of L-tryptophan to niacin.

Niacin is biosynthesized from L-tryptophan. As a lot of L-tryptophan exists in the body, the pathway is very important because niacin can be efficiently supplied even when the body emergently needs niacin. Therefore, it is very important to know factors affecting the conversion ratio of L-tryptophan to niacin. The conversion ratio is decreased with increasing dietary protein levels. In the effects of fat, feeding of diets containing unsaturated fatty acids increased the conversion ratio, while feeding of diets saturated fatty acids did not. In the effects of carbohydrate, the conversion ratio was higher in diets containing starch than in diets containing sucrose.

Animals↗

Evaluation of preoperative and intraoperative arterial stimulation and venous sampling for diagnosis and surgical resection of insulinoma.

BACKGROUND: The precise intraoperative localization of insulinoma is essential for successful surgical treatment. In addition to various imaging modalities developed recently, arterial stimulation and venous sampling (ASVS) has also been used for tumor localization. METHODS: Preoperative and intraoperative ASVS procedures were performed in 6 patients with insulinoma. Intraoperative ASVS was performed before and after tumor resection. Immunoreactive insulin (IRI) concentrations and the IRI ratio (IRI concentration at each time interval after calcium injection/baseline IRI concentration) were determined by the conventional or a quick IRI method. RESULTS: The site of the tumor was identified preoperatively in all patients. The peak of the IRI ratio varied widely, but setting the cutoff value at 3.0 clearly differentiated peak IRA ratios in feeding arteries from those of nonfeeding arteries. Intraoperative ASVS showed a similar elevation of IRI levels, but the elevation disappeared after tumor resection in all but 1 patient. In 2 patients, resection of the tumor was confirmed during surgery by measuring IRI levels by the quick IRI method. CONCLUSIONS: A combination of ASVS and conventional imaging modalities is useful for precise localization of insulinoma. Resection of the tumor can be confirmed intraoperatively by comparing IRI levels associated with preoperative and postresective ASVS.

Adult↗

Attenuated hypotensive response to proadrenomedullin N-terminal 20 peptide in pregnant rats: modulation by steroid hormones.

The hypotensive effect of proadrenomedullin N-terminal 20 peptide (PAMP) was examined in conscious pregnant (8, 14, and 20 days of pregnancy) and nonpregnant rats. Intravenous administration of PAMP (3-60 nmol/kg) produced a dose-dependent depressor response in both pregnant and nonpregnant rats. However, the maximum decrease in blood pressure was significantly attenuated in pregnant rats in mid- and late-gestation (14 and 20 days), but not in early gestation (8 days), than in nonpregnant rats. In ovariectomized rats, the depressor responses in 17beta-estradiol (E2)-treated, progesterone (P)-treated, and E2+P-treated rats were significantly attenuated compared with the control rats. We also demonstrated that treatment of sex hormones reduces the depressor response to PAMP in 8-day pregnant rats. In addition, we showed that treatment of sex hormone receptor antagonists partially prevents the attenuation of the depressor response to PAMP in 20 day pregnant rats. These findings suggested that the hypotensive response to PAMP was more attenuated in pregnant rats in mid- and late-gestation than in nonpregnant rats, and that the changes in depressor response that occur at term in pregnant rats may be mediated by sex hormones. PAMP may play some important role in cardiovascular regulation during pregnancy.

Adrenomedullin↗

Carcinoma of the gallbladder associated with anomalous junction of the pancreaticobiliary duct in adults.

BACKGROUND: Anomalous junction of the pancreaticobiliary duct (AJPBD) is a congenital anomaly in which the junction is located outside the sphincter of Oddi. A high incidence of gallbladder carcinoma (GBC) has been reported in adult patients with AJPBD. STUDY DESIGN: Fourteen adult patients with AJPBD and 50 with GBC not associated with AJPBD were reviewed retrospectively to identify the clinical characteristics of AJPBD accompanied by GBC and to clarify the differences in clinicopathologic features between GBC associated with AJPBD and GBC without AJPBD. RESULTS: Among the 14 patients with AJPBD, there were five fusiform, four cystic, and two cylindric dilatations of the biliary tract and three nondilated bile ducts. Nine (64%) of 14 patients had GBC, five with fusiform dilatations, two with cylindric dilatations, and two with nondilated bile ducts. No patient with cystic dilatation had GBC. There were two stage I cancers, four stage II, two stage III, and one stage IVB. One patient with stage IVB GBC died of recurrence 8 months after operation. The remaining 8 patients were well without signs of recurrence from 8 to 72 months after operation. The frequency of grossly polypoid or histologically papillary adenocarcinoma was higher in GBC patients with AJPBD than in those without AJPBD (p < 0.01). The proportion of disease-free survivors was greater among GBC patients with AJPBD than among those without AJPBD (p < 0.05). CONCLUSIONS: AJPBD with noncystic dilatation or without dilatation appears to be an important risk factor for GBC. In this limited series, patients with GBC accompanied by AJPBD have had relatively favorable outcomes.

Adult↗

Possible involvement of central C-type natriuretic polypeptide receptor on water intake in spontaneously hypertensive rats, but not in normotensive Wistar-Kyoto rats.

The present study was designed to examine the possible role of brain C-type natriuretic polypeptide receptor (GC-B) in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto rats (WKY). The level of GC-B mRNA in various regions of the brain in both SHR and WKY was examined in the present study. The GC-B mRNA was unevenly distributed in rat brain, the transcript being expressed predominantly in the hypothalamus and cerebellum but comparatively at low level in the striatum and septum. However, the level in the septum was 3-fold higher in SHR than than in age-matched WKY, while no differences were observed in other regions of the brain. Intracerebroventricular administration of antisense oligonucleotide to GC-B mRNA inhibits the night-time water intake in SHR, but not in WKY. However, the daily food intake was not significantly altered by the injection of antisense oligonucleotide in both strains. These results demonstrate that the brain GC-B mRNA, particularly in septum, is increased in SHR and this increase may be closely related to the regulation of water-drinking behaviour in SHR.

Animals↗

Topological and functional characterization of the N-glycans of soybean (Glycine max) agglutinin.

Soybean agglutinin (SBA), is a noncovalently bound tetramer comprised of four identical subunits having a single N-glycan chain, Man9GlcNAc2, that is known to be essential for regeneration of the functional tetrameric structure from unfolded subunits. In this study, SBA was found to have strong affinity for concanavalin A, indicating that the N-glycans are extensively solvent-exposed. The susceptibilities of the N-glycans to alpha-mannosidase and endo-beta-N-acetylglucosaminidase revealed that their distal areas have nonreducing ends embedded among the subunits, whereas their proximal regions are solvent-exposed. Endo-beta-N-acetylglucosaminidase-digested SBA was unable to retain its conformation and gradually unfolded. Periodate-oxidized SBA, whose N-glycans closely correspond to the invariant pentasaccharide core, tended to dissociate into the subunits, but permitted to stay as folded monomers. This SBA species was capable of refolding from unfolded subunits but unable to form the functional tetramer. It seems probable that the proximal regions of the N-glycans function in the formation and stabilization of the subunit conformation, whereas the branches outside the invariant cores stabilize the tetrameric structure.

Carbohydrate Conformation↗