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H Higashino

Publications and source records attributed to H Higashino.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effects of insulin and insulin-like growth factor-1 on intracellular magnesium of platelets.

Magnesium (Mg2+), the second most abundant intracellular cation, is a critical cofactor in numerous enzymatic reactions. After stimulation of platelets with insulin and insulin-like growth factor-1 (IGF-1), we examined changes in cytosolic free Mg2+ ([Mg2+]i) by using fluorescent probe magfura-2. Basal [Mg2+]i in platelets was 614 +/- 1 microM (mean +/- SEM, n = 60). Insulin and IGF-1 induced an immediate rise of [Mg2+]i in a dose-dependent manner. After stimulation of platelets with 100 microU/mL of insulin for 60 s, [Mg2+]i was significantly elevated to 1270 +/- 53 microM (n = 30, P < 0.05), i.e., 82 +/- 5% over resting [Mg2+]i. IGF-1 (5 micrograms/mL) also increased [Mg2+]i (1020 +/- 53 microM, 69 +/- 10% over resting [Mg2+]i, n = 30). In the medium containing choline instead of sodium or the medium without potassium, an elevation of [Mg2+]i with addition of insulin/IGF-1 was moderately suppressed. Amiloride, a Na+-H+ antiport inhibitor, did not block the insulin/IGF-1 effect. Insulin/ IGF-1 translocates Mg2+ from the extracellular space to intracellular space and these effects are affected by external sodium and potassium.

Amiloride↗
PubMed1998

A patient with congenital lipoid adrenal hyperplasia evaluated by serial abdominal ultrasonography.

UNLABELLED: Adrenal enlargement was followed by serial ultrasonography in an infant with congenital lipoid adrenal hyperplasia (lipoid CAH) from day 12 until 2 years and 4 months of age, when they were no longer detectable. Contrary to other types of CAH in which the configuration changes soon after replacement therapy, this infant with lipoid CAH showed persistent adrenal cortex enlargement due to massive accumulation of lipids and cholesterol resulting in a damaged glandular cyto-architecture. CONCLUSION: ultrasonographically persistent enlargement of the adrenals after replacement therapy is suggestive of the lipoid form of CAH.

Adrenal Cortex↗
PubMed1997

Quantitative analysis of myocardial ischemia by technetium-99m sestamibi exercise scintigraphy: a new method for change rate mapping.

In order to quantitatively assess the extent and severity of myocardial ischemia by Tc-99m sestamibi exercise myocardial scintigraphy, we developed a new method of change rate (CR) mapping and examined its efficiency. CR was calculated to divide the counts per pixel in the stress polar map by that in the rest polar map at each corresponding pixel. The CR map showed the CR values at each pixel. To correct the differences between the stress and rest images for the dose of Tc-99m sestamibi administered, the mean counts per pixel in the stress polar map and the rest map were adjusted to the same level. Regarding the regions in which the CR value was less than 1 as ischemia, we compared the abilities of the CR map and the polar map to detect coronary artery stenosis in 5 patients with angina pectoris. The sensitivity for coronary artery stenosis was 80% in the CR map, and 40% in the polar map. The specificity for both was 75%. We concluded that the CR map was effective in assessing the extent and severity of myocardial ischemia in Tc-99m sestamibi exercise myocardial scintigraphy.

Adult↗
PubMed1997

Altered intracellular calcium and phorbol 12,13-dibutyrate binding to intact platelets in young obese subjects.

The study was designed to examine cytosolic free calcium ((Ca2+)i) and phorbol dibutyryl ester binding in intact platelets of young obese subjects as compared with the platelets of age-matched subjects with non-insulin-dependent diabetes mellitus (NIDDM) and those of healthy control subjects. The assay was studied in basal and thrombin-stimulated conditions. The binding parameter of phorbol ester is a criterion for active protein kinase C (PKC) units in the platelet plasma membrane. The resting (Ca2+)i correlated with body mass index (BMI)(r = 0.385, p = 0.0034) and plasma insulin level (r = 0.316, p = 0.0269), and the resting (Ca2+)i level was higher in the obesity group (160.6 +/- 15.8 nmol/L; n = 25) than controls (78.9 +/- 7.6 nmol/L; n = 24, p < 0.0001). Among the obesity and control groups, there was a correlation between BMI and fasting plasma insulin level (r = 0.399, p = 0.0237). Systolic blood pressure correlated with BMI(r = 0.504, p = 0.0005). The mean systolic blood pressure of the obesity group was higher than those of the other two groups. The mean Hill coefficient for thrombin-treated platelets of phorbol dibutyrate binding was higher in the obesity group when compared with healthy controls and the subjects with NIDDM (1.47 +/- 0.21 vs 1.06 +/- 0.16 and 0.99 +/- 0.09, respectively; p < 0.05). In conclusion, young subjects with simple obesity have already developed altered platelet Ca2+ regulation that is usually observed in adult patients with a number of metabolic diseases. These data are interpreted to indicate that a relationship exists between dysregulation of PKC and impaired glucose tolerance that precedes other complications of obesity.

Adolescent↗
PubMed1997

Increased intracellular calcium and altered phorbol dibutyrate binding to intact platelets in young subjects with insulin-dependent and non-insulin-dependent diabetes mellitus.

Intracellular calcium ([Ca2+]i) and phorbol ester binding were studied in intact platelets of young patients with insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus. Our objective was to evaluate disturbances in calcium regulation and signal transduction in platelets of diabetics. [Ca2+]i in platelets of the IDDM group (135 +/- 20 nmol/L) under basal conditions was significantly higher than that of the control group (81 +/- 8 nmol/L, P = .019), whereas at 60 seconds after stimulation with 0.1 National Institutes of Health (NIH) U/mL thrombin, [Ca2+]i in the NIDDM group (484 +/- 36 nmol/L) was significantly higher than that of the controls (347 +/- 22 nmol/L, P = .003) and IDDM group (360 +/- 45 nmol/L, P = .04), respectively. Phorbol 12,13-dibutyrate (PdBu) maximal binding capacity (Bmax) in the IDDM group was significantly lower than that in the control group either under basal conditions or after stimulation with thrombin (P = .0034 and P = .015, respectively). Bmax in the NIDDM group was significantly lower than that in the controls only after stimulation with thrombin (P = .047). The Kd for PdBu of the IDDM group was lower than that of the control group under basal conditions (P = .017). When analyzing the pooled data of all subjects, a significant correlation was observed between Bmax and Kd (under basal conditions, r = .544, P < .0001; after stimulation, r = .601, P < .0001). Our results support the idea that the increased affinity for PdBu may compensate for the decreased binding capacity. We interpret the data as indicating that the change in the binding of phorbol ester to protein kinase C (PKC) units may result in an altered PKC/calcium interaction in the pathogenesis of diabetes mellitus. Our study indicates that such metabolic derangements of [Ca2+]i have already been developing in young diabetic patients.

Adolescent↗
PubMed1996

Glycation decreases the stability of the triple-helical strands of fibrous collagen against proteolytic degradation by pepsin in a specific temperature range.

When fibrous collagen of rat tail tendons was glycated by incubation with ribose, it became highly insoluble in dilute acetic acid and resistant to pepsin digestion at 5 degrees C, since it was cross-linked by advanced glycation end products. Extensively glycated fibrous collagen was found to be much less stable than non-glycated control fibrous collagen against pepsin digestion at 30 degrees C. Under conditions where nearly all of the glycated fibrous collagen was degraded into small peptides by pepsin, approximately 45% of the control collagen was left as large polypeptides having nearly the whole length of its triple-helical region. A soluble collagen, which consisted primarily of the triple-helical region of monomeric collagen, was found to be glycated as efficiently as the fibrous collagen on incubation with ribose at 30 degrees C, while the rate of cross-linking of the soluble collagen was very low, suggesting that the triple-helical strands do not undergo intramolecular cross-linking and that most of the cross-links produced in the glycated fibrous collagen are intermolecular ones. The glycated soluble collagen was as stable as the control collagen against pepsin digestion at 30 degrees C. These results indicate that the triple-helical strands of glycated fibrous collagen are much less stable than those of the non-glycated form against proteolytic digestion by pepsin at a temperature close to but below their melting point. Sugar-derived intermolecular cross-links are supposed to underly the decreased stability of the triple-helical strands.

Acetic Acid↗
PubMed1996

[Clinical study of a macrolide antibiotic, azithromycin, in pediatric patients].

Azithromycin (AZM), 10% fine granules or 100 mg capsules, were given orally to 27 children with various pediatric infections. The results of the study are shown below. 1. Pharmacokinetic investigation. We studied plasma and urinary concentrations after 100 mg AZM capsules were given. One patient received 8.3 mg/kg of AZM once a day for 3 days, and AZM concentration in plasma was 0.033 microgram/ml 48 hours after the final dosing. Doses of 8.3 and 12.5 mg/kg body weight of AZM were respectively given to two patients once daily for 3 days. As a result, AZM concentrations in urine during a period between 96 and 120 hours post-dosing were 1.67 and 4.53 micrograms/ml, respectively, and urinary excretion rate in 120 hours after the first dosing was 10.54% in the patient that was given 12.5 mg/kg. 2. Clinical investigation. Clinical efficacies were examined in 24 patients. Excellent results were obtained in 7 patients, good results in 14 patients, hence the clinical efficacy rate was 87.5%. Bacteriologically, Haemophilus influenzae strains isolates from 2 patients were eradicated in 1 and decreased in the other. Safety was evaluated in 26 patients. An adverse reaction was observed in 1 patient (urticaria). Abnormal laboratory test results were observed in 2 patients, decreased WBC in 1 and elevation of eosinophils in the other. The above results suggest that AZM is a useful oral antibiotic for pediatric patients with infection with susceptible organisms.

Adolescent↗
PubMed1995

The mechanism of interaction of sodium dodecyl sulfate with elastic fibers.

Sodium dodecyl sulfate (SDS), an anionic hydrophobic ligand, is known to alter the mechanical properties of elastic fibers. In order to analyze the mechanism of the alteration, two forms of fibrous elastins, "solid" and "powder" elastins, which consisted of fascicular elastic fibers and single or oligomeric elastic fibers, respectively, were prepared from bovine aorta, and the interactions of SDS with these elastins in the presence and absence of 0.15 M NaCl were studied. The solid elastin was able to retain 1.2- to 1.4-fold larger amounts of SDS than the powder elastin under both conditions, and both elastins retained 1.2-fold or larger amounts of SDS in the presence of NaCl than in its absence. Whereas both elastins released the retained SDS gradually on repeated washing with an SDS-free buffer, the release rates from the solid elastin, especially the rate in the presence of NaCl, were much smaller than those from the powder elastin, and the solid elastin retained approximately 40% of the bound SDS under conditions where the powder elastin lost most of its SDS. The SDS-binding capacities of both elastins were significantly lower than those of soluble kappa-elastin and serum albumin, which bound SDS homogeneously on the polypeptide chains. When the washed SDS-bound solid elastin was incubated with methylene blue and examined under a microscope, most of the methylene blue-SDS complex was located at the interfiber spaces of the elastic fibers. These results suggest that SDS alters the mechanical properties of elastic fibers by binding to the interfiber spaces and surfaces of the fibers rather than by binding to the internal polypeptide chains.

Animals↗
PubMed1995

Biochemical characterization of the fibres of collagen and elastin in the aortic wall of SHRSP.

1. Vessel wall fragments consisting of collagen, elastin and other insoluble proteins were prepared from the aortas of 6 month old WKY and SHRSP and dead, elderly humans. 2. Prolonged incubations of these fragments with pepsin below or at 30 degrees C resulted in different amounts of insoluble materials containing similar or larger proportions of collagen and other insoluble proteins than the respective vessel fragments. The amounts of the pepsin-insoluble materials obtained from SHRSP were larger than those from WKY but were much smaller than those from elderly humans. 3. The elastins isolated from the vessel fragments were solubilized by pepsin much more effectively than the respective vessel fragments. 4. The pepsin-insoluble materials from WKY were composed of thin mesh-shaped materials, while these materials from both rats did not contain a significant number of distinctive fibrils of collagen, the materials from elderly humans did contain numerous distinctive fibrils of collagen. 5. Large fractions of both the collagen and other proteins in the pepsin-insoluble materials were solubilized by incubation with a crude bacterial collagenase below 30 degrees C or by incubation with pepsin above 40 degrees C where the triple-helical regions of the collagens were unfolded. 6. These results appear to indicate that the aortic wall of SHRSP contains larger amounts of some insoluble components that immobilize the collagen fibrils than that of WKY, but the aortic walls of elderly humans contain much larger amounts of these components than that of SHRSP.

Aged↗
PubMed1995

Haemodynamic effects of NO-synthase inhibitors, NG-monomethyl-L-arginine, NG-nitro-L-arginine and NG-nitro-L-arginine methyl ester, and NO-donor, glyceryl trinitrate, in conscious SHRSP and WKY.

1. The experiments were carried out by an ordinary and a microsphere method in order to clarify the effects of three nitric oxide-synthase inhibitors and -donor on the circulating system between SHRSP and WKY. 2. Intravenous administration of each compound possessing the nitric acid-synthase inhibiting action markedly elevated the systolic blood pressure both in SHRSP and WKY, but more prominently in the former. 3. The hypotensive and tachycardic responses to glyceryl trinitrate were more enhanced after treatment with NG-nitro-L-arginine and NG-nitro-L-arginine methyl ester but not with NG-monomethyl-L-arginine compared with the non-treated one. 4. All peripheral organs except the brain decreased their regional blood flow after administration of NG-nitro-L-arginine, indicating a crucial involvement of nitric oxide in the peripheral circulation. 5. It was suggested that the nitric oxide system worked more sensitively and actively in SHRSP than in WKY in order to maintain the peripheral blood flow and systemic blood pressure.

Animals↗
PubMed1995

Comparative haemodynamic studies of endothelin-1, -2 and -3 on conscious SHRSP and WKY.

1. Depressor and pressor effects of endothelin-1, -2 and -3 in relation to hypertension were investigated in conscious WKY and SHRSP. 2. Changes of systolic arterial pressure to both depressor and pressor responses caused by three doses of endothelin-1, -2 or -3 (0.1, 0.3 and 1 nmol/kg) occurred to a similar extent between WKY and SHRSP. These data showed that endothelins may not exert an important role on the pathogenesis of hypertension. 3. Endothelin-1 decreased the cardiac index more in SHRSP than in WKY, indicating the dominance of ETA receptors in SHRSP compared with WKY. 4. ET-1 was the most potent vasodepressor and vasodilator of three endothelin peptides in rats. 5. During the pressor responses to endothelin-1 and -3, cardiac arrhythmia was observed with high frequency in the animals of both groups, indicating the arrhythmogenic effect of ET.

Animals↗
PubMed1995

Placental Na+, K+ activated ATP-ase activity in SHRSP in connection with pregnancy induced hypertension and intra-uterine growth retardation.

1. Placental Na+, K+ -ATPase activities were measured in connection with the active transport of amino acid, intra-uterine growth retardation (IUGR) or small for date infants (SFD) in salt-loaded pregnant SHRSP. 2. All parameters such as fetal weight, placental weight and Na+, K+ -ATPase activity in the placental tissue were significantly depressed in SHRSP, especially in the salt-loaded SHRSP compared with WKY. 3. Besides a decrease of blood flow, a decline of Na+, K+ -ATPase activity associated with an active transport of amino acid in the placenta would cause IUGR and SFD in the salt-loaded pregnant SHRSP. 4. Pregnant SHRSP given water containing salt would be a good model for pregnancy induced hypertension in humans.

Animals↗
PubMed1995

Proper measurement of blood pressure and heart rate in SHRSP and WKY by an indirect volume-oscillometric method.

1. The effect of environmental temperature on the indirect measurement of rat blood pressure and heart rate was investigated with special reference to the tail arterial blood flow in both strains of SHRSP and WKY. 2. Very good correlations (r > 0.82, P < 0.05; t-test, 10 d.f.) were observed between the two values of systolic blood pressure or heart rate measured by a direct and an indirect method at environmental temperatures between 26 and 38 degrees C in SHRSP, and 34 and 38 degrees C in WKY, respectively. 3. When the temperature was elevated by 10 degrees C from 25 degrees C to 35 degrees C, the regional blood flow in the tail artery increased by 52-69%, sufficient to detect a blood flow increase by the indirect method. 4. These data showed that the best way to measure the accurate blood pressure and heart rate in both strains of SHRSP and WKY by the indirect volume-oscillometric method was to hold the rats at 34-36 degrees C for 5 min.

Animals↗
PubMed1995

Renin-angiotensin system in the antihypertensive effect of isoteoline in spontaneously hypertensive rats.

1. The aim of the present study was to examine the effects of isoteoline (IST), a new tetrahydroaporphine derivative, on the blood pressure and some of the components of renin-angiotensin-aldosterone system (RAAS) in spontaneously hypertensive rats (SHR). 2. After long-term treatment (14 days, 3 times daily) in a dose of 1 mg/kg orally and intraperitoneally, IST induced a significant decrease of the systolic blood pressure (SBP) in SHR (from 192 +/- 2 to 155 +/- 5 mgHg). 3. At the same time, IST induced a significant decrease of the levels of plasma renin activity (PRA) and aldosterone (ALD) and manifested a trend to increase the sodium plasma level. 4. These results indicate that IST after chronic long-term treatment induced a marked antihypertensive effect and inhibited the components of RAAS in SHR. Apparently, the long-lasting antihypertensive effect of IST in SHR was mediated and realized in part by inhibition of the components of RAAS.

Aldosterone↗
PubMed1995

[Clinical evaluation of a new oral penem, SY5555, in infants and children].

A clinical study was performed on SY5555, a newly developed penem antibiotic, in children. SY5555 was given orally to 14 patients at 19-29 mg/kg/day in 3 doses for 4 to 12 days. Clinical evaluations were made on the 14 patients including 4 with pharyngitis, 7 with tonsillitis, one with urinary tract infection, and 2 with impetigo. Overall clinical effects were excellent in 2, good in 12, with an efficacy rate of 100%. Causative organisms (Staphylococcus aureus and Streptococcus pyogenes) were all eradicated. As to adverse reactions, mild diarrhea was observed in 4 patients. These data suggest that SY5555 is a useful oral antibiotic for the treatment of bacterial infections in children.

Administration, Oral↗
PubMed1994

Changes in Ca2+ mobilization in platelets from stroke-prone spontaneously hypertensive rats.

Intracellular free Ca2+, [Ca2+]i, levels were measured in platelets from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) using fura-2AM. In the presence of extracellular Ca2+ (1 mM), [Ca2+]i levels in unstimulated platelets of 2- and 9-month-old SHRSP were both significantly higher than those of the age matched WKY. In the absence of extracellular Ca2+, the levels in platelets from 9-month-old SHRSP were also higher than any other groups examined. Receptor-linked Ca2+ influxes of old SHRSP were smaller when thrombin or collagen was given to the platelets. Phorbol 12-myristate 13-acetate (TPA) enhanced more prominently the Ca2+ influx into old SHRSP platelets than into old WKY platelets. These results strongly suggest that the Ca2+ permeability across plasma membrane is increased in young as well as old SHRSP platelets, where the resting [Ca2+]i level is highly sustained because of an impaired Ca2+ uptake mechanism and possible enhancement of protein kinase C activity.

Animals↗