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Biomedical subjects

S Hashimoto

Publications and source records attributed to S Hashimoto.

At least 145 records · Page 8Linked to original sources
PubMed1990

Pharmacological subclassification of alpha 1-adrenoceptors in vascular smooth muscle.

1. We examined whether alpha 1-adrenoceptors in various blood vessels can be divided into subtypes by antagonist affinity or by susceptibility to chloroethylclonidine or nifedipine. 2. Noradrenaline or phenylephrine produced concentration-dependent contractions in all the tissues tested, which were competitively inhibited by phentolamine, yohimbine, prazosin, WB4101 and HV723. However, there were large differences between the tissues in the pA2 values for all the antagonists except phentolamine. 3. The blood vessels could be classified into three groups (I, II and III) on the basis of their affinity variation. In group I (dog mesenteric artery and vein, saphenous vein), the pA2 values for HV723 were greater than 9, and those for HV723 and WB4101 were approximately 1 log unit higher than for prazosin. This rank order of affinity reversed in group II (dog carotid artery and rat thoracic aorta), where prazosin was more potent (pA2 values greater than 9.5) than HV723 or WB4101. In group III (rabbit mesenteric artery, thoracic aorta and carotid artery and guinea-pig thoracic aorta), on the other hand, prazosin, HV723 and WB4101 inhibited the noradrenaline response with a similar affinity (pA2 values ranging from 8 to 9). 4. Yohimbine inhibited the responses to noradrenaline and phenylephrine with a lower affinity than prazosin, HV723 or WB4101. The pA2 values for yohimbine were similar in groups I and II (the values greater than 6.5), which were greater than those in group III (values less than 6.4). 5. The alpha l-adrenoceptors in group II were selectively affected by chlorethylclonidine, resulting in an irreversible attenuation of noradrenaline responses in the dog carotid artery and a persistent contraction in the rat thoracic aorta. 6. Nifedipine either produced no effect or a slight inhibition of alpha l-adrenoceptor-mediated contractions in all the blood vessels; these effects were not correlated to the above groups. 7. These results suggest that alpha,-adrenoceptors of blood vessels can be divided into three subtypes (designated as alpha 1H, alpha4L and alpha 1N) by antagonist affinity and their susceptibility to chloroethylclonidine but not to nifedipine: the characteristics of each subtype are summarized in Table 3. Subtypes alpha lH, alpha 1L and alpha lN may be predominantly involved in the contractile responses to noradrenaline or phenylephrine of the blood vessels in groups II, III and I, respectively.

Acetonitriles↗
PubMed1990

Liposome distribution after intravenous and selective intraarterial infusion in dogs.

In an effort to improve hepatic uptake of liposomes for drug delivery, empty vesicles were administered by means of selective arterial infusion. Negatively charged, multilamellar liposomes were labeled with technetium-99m and infused into healthy adult dogs. Each dog received 100 mg/m2 of lipid over 10 minutes at 2 mL/min. Liposomes were administered via the common hepatic artery after proximal occlusion of the gastroduodenal artery, via the cranial mesenteric artery, and via the cephalic vein. Distribution (liver, spleen, and lungs) was determined by computer-assisted external imaging techniques. On the average, after arterial infusion, 69.2% of the total activity was located in the liver, 3.6% in the spleen, 3.2% in the lungs, and 3.5% in the general circulation. Following venous injection, 50.7% of the radioactivity was found in the liver, 9.1% in the spleen, 8.6% in the lungs, and 6.7% in the peripheral blood. Once the liposomes entered the systemic circulation, they were cleared at the same rate (half-life beta = 21.5 hours) independent of their route of administration. Increased hepatic liposome uptake should translate into higher local and lower systemic liposomal drug levels.

Animals↗
PubMed1990

Fibroblast growth factor-induced decrease in the phosphorylation of Nsp100 mediated through a calcium-dependent mechanism and blocked by lectins.

Separate treatment of PC12h cells with basic fibroblast growth factor (bFGF) and with epidermal growth factor (EGF) induced a selective decrease in the incorporation of radioactive phosphate into a 100,000-dalton soluble protein during phosphorylation with (gamma-32P)ATP of soluble extracts from the cells, as was seen previously with nerve growth factor (NGF). This 100,000-dalton soluble protein was designated in earlier studies as nerve growth factor-sensitive protein 100 (Nsp100). The inhibitory effects of bFGF and EGF on Nsp100 phosphorylation were prevented by pretreatment of PC12h cells with the calcium chelator, EGTA. Treatment of PC12h cells with the plant lectin wheat germ agglutinin (WGA), which binds to N-acetylglucosamine and sialic acid residues on glycoconjugates, blocked the inhibitory effects of bFGF, EGF, and NGF on Nsp100 phosphorylation. The blockage by WGA was reversed by the addition of the lectin-specific sugar N-acetylglucosamine to the PC12h cultures. Although pretreatment of PC12h cells with succinylated WGA, which has the ability to bind to N-acetylglucosamine but not to sialic acid residues, failed to block the inhibitory effect of NGF on Nsp100 phosphorylation as described previously, it did prevent the inhibitory effect of bFGF on this phosphorylation. These data suggest that in PC12h cells bFGF and EGF induce a decrease in the phosphorylation of Nsp100 mediated through a Ca2(+)-dependent mechanism, as in the case of NGF. Furthermore, the blockage of the bFGF-induced inhibition of Nsp100 phosphorylation by WGA and its succinylated form indicates that N-acetylglucosamine residues of bFGF receptor molecules might be involved in the mechanism by which bFGF inhibits the phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗
PubMed1990

Effects of exercise on coronary risk factors in obese, middle-aged subjects.

The effects of exercise (10000 walk steps/day) and diet (1500 kcal/day) for 4 months on coronary risk factors (obesity, hypertension, serum lipid and lipoprotein abnormalities) were studied in 332 obese, middle-aged subjects. Body weight, skinfold thickness, systolic and diastolic blood pressures, serum lipid and lipoproteins (total cholesterol, triglyceride, and beta-lipoprotein) improved significantly (p less than 0.05) during the program. The degree of improvement in blood pressures, serum lipids and lipoproteins was greater in abnormal blood pressure (greater than 140/90 mmHg) or abnormal serum lipid group than in normal group. A significant correlation was observed between daily number of walk steps and the improvement of body weight, diastolic blood pressure and HDL-cholesterol. Increase of daily steps during the program showed a significant (p less than 0.05) correlation to the change in HDL-cholesterol. It was suggested that mild exercise characterized by brisk walking was effective in the treatment of obesity, hypertension and low HDL-cholesterolemia in obese, middle-aged subjects.

Blood Pressure↗
PubMed1990

Effect of nicardipine hydrochloride on circulating blood volume and vascular compliance in dogs.

We studied the effect of nicardipine on the canine cardiovascular system, especially on total blood volume and vascular compliance. Under light halothane anesthesia, nicardipine decreased total blood volume significantly (from 80.0 +/- 8.4 ml/kg in the control state to 75.3 +/- 8.0 ml/kg under nicardipine administration, p less than 0.01), while it increased central circulating blood volume (from 17.1 +/- 5.9 ml/kg to 25.5 +/- 8.2 ml/kg, p less than 0.01), increased cardiac output and central venous pressure, and decreased mean arterial pressure (from 134.3 +/- 16.2 mmHg to 93.9 +/- 17.1 mmHg, p less than 0.01) and total peripheral resistance. Vascular compliance derived from fluid infusion experiments showed a significant decrease (from 8.9 +/- 3.8 ml/mmHg/kg to 5.5 +/- 8.0 ml/mmHg/kg, p less than 0.01). In addition to the vasodilatory action of nicardipine on arteries, these findings also suggest that 1) nicardipine causes a fluid shift from the vascular to the interstitial fluid space as a result of increased capillary pressure, 2) it increases preload through blood redistribution from the peripheral to the central circulation, and 3) it decreases compliance of the vessels, perhaps due to an indirect splanchnic venoconstriction.

Animals↗
PubMed1990

[Evaluation of serum S100ao protein in patients with renal cell carcinoma].

In order to evaluate the clinical significance of S100ao protein, we measured serum S100ao protein in 36 patients with renal cell carcinoma by EIA developed by Kimura et al. In addition, the distribution of S100ao protein was studied by the immunohistochemical method. Previous study demonstrated that mean level of serum S100ao protein in healthy volunteers was 203 +/- 107 pg/ml, therefore the cut off level was set to 524 pg/ml. The results obtained in this study were as follows: 1) The mean level of serum S100ao protein was 1162 +/- 2056 pg/ml, and its positive rate was 44% in 36 patients with renal cell carcinoma. When the patients were divided into 2 groups according to tumor stage, the mean level of serum S100ao protein in the high stage group was significantly higher than that in the low stage group (p less than 0.01). 2) In the sequential study of serum S100ao protein, patients with progressive disease showed a gradual increase in the level of serum S100ao protein while patients with no evidence of tumor showed a normal level of serum S100ao protein. 3) There was no correlation between the level of serum S100ao protein and the histological grade of renal cell carcinoma. 4) Immunohistochemical analysis (10 cases) showed that S100ao protein was observed in all of 10 renal cell carcinomas. Thus, the present study suggests that serum S100ao protein might be a useful clinical marker especially in monitoring patients with renal cell carcinoma.

Adult↗
PubMed1990

Studies on new dehydropeptidase inhibitors. III. Biological properties of WS1358A1.

WS1358A1, a novel inhibitor of renal dehydropeptidase (DHP), augmented the urinary recovery of a carbapenem antibiotic imipenem and improved its protective effect in experimental infections when simultaneously administered to mice with the antibiotic. WS1358A1 was a competitive DHP inhibitor with a Ki value of 1.6 x 10(-7) M.

Animals↗
PubMed1990

FR112123, a new oligopeptide antibiotic from Streptomyces viridochromogenes. Taxonomy, fermentation, isolation, physico-chemical properties, structure and biological activity.

FR112123 is a new oligopeptide antibiotic produced by Streptomyces viridochromogenes No. 7587. The structure of FR112123 is elucidated as N-(N6-(N2-glycyl-L-glutaminyl)-D-lysyl)-D-alanine (1) by spectroscopic and chemical evidence. It resembles a partial structure of peptidoglycan in bacteria. The compound has a superior activity against an Escherichia coli mutant sensitive to inhibitors of cell wall synthesis, although it has a weak activity against the parent strain. These suggest that FR112123 might act on the biosynthesis of bacterial cell wall.

Animals↗
PubMed1990

Synthesis and structure determination of FR109615, a new antifungal antibiotic.

The structure of FR109615, a new antifungal antibiotic, was determined to be (1R,2S)-2-aminocyclopentane-1-carboxylic acid ((-)-cis-2-ACPC: 8a) by X-ray analysis. (-)-cis-2-ACPC (8a) was also synthesized via optical resolution of 3a and 3b derived from (+/-)-cis-2-ACPC hydrochloride (1). 8a showed potent antifungal activity, while its antipode (+)-cis-2-ACPC (8b) had no activity.

Antifungal Agents↗
PubMed1990

In vitro effect of thymic epithelial culture supernate on cyclic GMP levels in rabbit platelets.

When supernatants of thymic epithelial cell cultures (STEC) or thymosin fraction 5 were incubated with washed platelets (37 degrees C for 30 min), the levels of platelet guanosine 3',5'-cyclic monophosphate (cyclic GMP) were increased in a dose-dependent manner. In contrast the supernatants from Chang, HeLa, or HCC-M cell cultures did not significantly affect the levels of intracellular cyclic GMP. The increment of intracellular cyclic GMP levels following treatment with STEC increased with longer incubation times until a plateau was reached at 30 min. This activity of STEC was found in fractions with a molecular weight below 10,000 daltons. Contents of guanine and guanosine in STEC were lower than those observed in other culture supernatants. STEC did not affect guanylate cyclase activity in platelets, but significantly inhibited cyclic GMP phosphodiesterase activities in platelet soluble and membrane fractions. Thymosin fraction 5 inhibited the phosphodiesterase activity of the soluble but not the membrane fraction.

Animals↗
PubMed1990

[Transesophageal Doppler echocardiography in the diagnosis of atrial septal defect].

To assess the usefulness of transesophageal Doppler echocardiography (TEE) in diagnosing atrial septal defect (ASD), we studied eight cases with secundum type ASD, in which the diagnosis was confirmed by cardiac catheterization and surgery. In all cases, TEE provided clear images of the interatrial septum with its defect. Shunt flow through the defect was observed by color Doppler technique, and its velocity was measured using the FFT mode. In two cases, right-to-left shunt blood flow was detected. Two types of probes were used in this study, a lateral scanning probe and a longitudinal scanning probe. The scanning plane of the former was perpendicular to the axis of the probe, and that of the latter was parallel to it. The two probes facilitated the measurement of the two right-angled dimensions, with which we could calculate the defect area, assuming the defect to be an ellipse. The volume of a left-to-right shunt was obtained by multiplying the defect area by the integration of flow velocity against time. Shunt volume per cardiac cycle obtained by this method correlated well with that obtained by the Fick's method during cardiac catheterization. In six cases without a right-to-left shunt, the coefficient of correlation was 0.98, and in all eight cases it was reduced to 0.72. Thus, we concluded that TEE is useful for diagnosing and evaluating ASD.

Adolescent↗
PubMed1990

[Clinical usefulness of transesophageal Doppler echocardiography].

The usefulness of transesophageal Doppler echocardiography (TEE) was assessed in patients with various cardiovascular diseases including 15 patients with dissecting aortic aneurysm (DAA), two with thoracic aneurysm, 16 with ischemic heart disease and 14 with acquired valvular diseases. In dissecting aortic aneurysms, TEE provided clear images of the intimal flaps even in the aortic arch and descending aorta in which clear images could not be obtained by conventional external Doppler echocardiography. The entry site was detected in 11 of the 15 (73%) cases using TEE, but in only three of the 15 cases using conventional Doppler technique. In two cases of true aortic aneurysms, TEE provided clear images of the aneurysm in the descending thoracic aorta, which was discriminated precisely from DAA. In valvular disease, all four valves (aortic, pulmonary and atrio-ventricular valves) were easily observed without disturbance by any other tissues using a transesophageal approach. In addition, valve aneurysms in the posterior mitral leaflets were detected using TEE in two cases. In two cases of mitral stenosis, a thrombus was observed in the left atrial appendage. These findings were confirmed during surgery, but could not be obtained by the conventional external studies. In 16 cases, TEE was performed during aorto-coronary bypass surgery under general anesthesia. In two of these cases, left ventricular assist devices were applied after surgery. In these cases, where conventional Doppler echocardiography was not applicable, cardiac function could be monitored by TEE. Thus, TEE is useful not only in evaluating morphological function in the cardiovascular system but also in monitoring cardiac hemodynamics during and after heart surgery.

Adult↗
PubMed1990

[A study of growth prediction of low-birth-weight infants].

To predict the time required for low-birth-weight (LBW) infants to catch-up with standard weight, the growth curves for weight in 156 LBW infants with no medical abnormalities were examined. The proportion of infants who caught-up with standard weight by 1.5 years of age was significantly higher in appropriate-for-dates (AFD) infants than in small-for-dates (SFD) infants (93% vs. 70%). The age of catch-up with standard weight had a significant inverse correlation with birth weight in AFD infants, and not in SFD infants. The age of catch-up standard weight of AFD infants, as predicted by the regression analysis was 4-8 months for 2,000 g of birth weight, 8-12 months for 1,500 g, and 12-15 months for 1,000 g, with about 80% accuracy. This prediction may be valuable in providing health advice to mothers with LBW infants.

Age Factors↗