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Biomedical subjects

Y Higashi

Publications and source records attributed to Y Higashi.

At least 73 records · Page 4Linked to original sources
PubMed2000

Abnormal Ca2+ handling and increased Mg2+ permeability in platelets of hypertensive rats.

In order to test the hypothesis that intracellular Na+ accumulation and cellular Mg2+ deficiency may be involved in the abnormalities in Ca2+ handling and reactivity in spontaneously hypertensive rats (SHR) platelets, the metabolism of Na+, Ca2+ and Mg2+ was determined in fluorescent dye loaded platelets from 15 SHR and 15 Wistar-Kyoto rats (WKY) at 12 weeks of age. Mg2+ leak was estimated as the Mg2+ influx induced by an increase in extracellular [Mg2+] (from 1 to 5 mmol/l) and Mg2+/Na+ exchange activity was estimated as the Mg2+ influx induced by a decrease in extracellular [Na+] (from 140 to 50 mmol/l). Cellular metabolism of the fluorescent dye was similar in the two groups. Mean platelet [Ca2+]i was significantly increased under basal and thrombin (0.1 U/ml)-stimulated conditions in SHR compared to WKY, both in the presence and absence of extracellular Ca2+. Mean Ca2+ discharge capacity was similar between the two groups. There was no difference in mean [Na+]i between the two groups. Basal [Mg2+]i was also increased in SHR platelets. Mg2+ leak was higher in SHR than in WKY, while Mg2+/Na+ exchange activity was similar in the two groups. There was no difference in serum Mg2+ concentration between SHR and WKY. These data suggest that abnormal Ca2+ handling is accompanied by elevation in [Mg2+]i via increased permeability of platelet cell membranes to Mg2+ in SHR without any alteration in [Na+]i, and do not support the Mg2+ deficiency hypothesis in genetically hypertensive rats.

Animals↗
PubMed2000

Immunohistochemical localisation of epidermal growth factor, transforming growth factor alpha and EGF receptor during organogenesis of the murine hypophysis in vivo.

In previous study of melanocyte-stimulating hormone (MSH) cell development in the proliferating pars intermedia, which is in close apposition to the presumptive pars nervosa, no direct cell-to-cell contact was found between the boundary neurohypophyseal pituicytes (PIC), adenohypophyseal precursor stem cells (PSC) and the related diencephalic mesenchymal cells. Here, we have used immunohistochemistry to examine cytokine expression in the development of the hypophysis during foetal stages II-IV. Light and confocal laser scanning microscopy indicated diffuse expression of both TGF alpha and EGF in the hypophysis at different foetal stages. While no findings indicative for temporary changes of TGF alpha and EGF patterns were found in the foetal hypophysis, a temporary increment of EGF molecules was distinct in the diencephalic mesenchyme at stages III and IV. On the other hand, light microscopy intensively immuno-localized EGFR in the adenohypophysis and neurohypophysis at different developmental stages. Immunoreactivity of EGFR in the cytoplasm and nucleus suggested active proliferative events in the PIC and PSC of stages II-IV mouse pituitaries.

Animals↗
PubMed2000

Abnormal magnesium status in patients with cardiovascular diseases.

To investigate magnesium status in patients with cardiovascular diseases and in those presenting high factors for these diseases, we measured the concentrations of serum total Mg, serum ionized Mg and intra-erythrocyte Mg. Mg is an important cofactor for many enzymes, especially those involved in phosphate transfer reactions. Mg deficiency has been shown to be associated with fatal cardiovascular diseases, as well as with risk factors for these diseases. Only measurement of the serum concentration of total Mg is routinely available, but ionized Mg is the physiologically active component. Furthermore, most of the body's Mg is present in the intracellular space. Subjects included patients with ischaemic heart disease (n=80), cardiac arrhythmia (n=60), diabetes mellitus (n=36), essential hypertension (n=194) and hypercholesterolaemia (n=60). The same measurements were made in healthy controls (30 men and 26 women; mean age 58+/-11 years). The serum ionized Mg concentration was measured with a selective ion electrode. The intra-erythrocyte Mg concentration was measured by atomic absorption. No gender difference was found for any Mg parameter, nor was age related to any Mg parameter. The serum albumin concentration was positively correlated only with the serum total Mg concentration. Although the serum total Mg concentration was similar in all groups, patients with diabetes mellitus and arrhythmia had lower serum levels of ionized Mg. Patients with essential hypertension exhibited higher intra-erythrocyte Mg concentrations than the healthy controls. Thus the measurement of serum total Mg concentration may obscure the presence of extracellular Mg deficiency in patients with arrhythmia and diabetes mellitus. Furthermore, the intracellular accumulation of Mg does not support the hypothesis of Mg deficiency in patients with essential hypertension.

Biomarkers↗
PubMed2000

[An investigation of factors associated with failure of extracorporeal shock wave lithotripsy for ureteral calculi].

In this study, we attempted to determine which patients with ureteral calculi are likely to have an unsuccessful outcome for extracorporeal shock wave lithotripsy (ESWL). The records of 388 patients with ureteral calculi treated with ESWL at Ijinkai Takeda General Hospital between January 1997 and December 1998 were retrospectively reviewed. Three hundred seventeen patients had been treated with ESWL alone (single session 156, multiple sessions 161) and 71 with transurethral ureterolithotripsy (TUL) due to failure of ESWL. We compared these two groups by multivariate logistic regression analysis, which revealed that (1) middle and lower ureteral calculi, (2) stones > 8 mm, (3) moderate to severe hydronephrosis and (4) failure of the first session ESWL were factors associated with poor outcome of ESWL. Although each predictive value of these factors was relatively low (29.6-38.6%), the rate of failure of ESWL was 85.0% when patients had all four factors. We therefore recommend an early change in treatment modality to TUL for patients with ureteral calculi when all four risk factors listed above are present.

Adult↗
PubMed2000

Scleroderma en coup de sabre with central nervous system involvement.

We describe a patient with scleroderma en coup de sabre and central nervous system symptoms. She presented with a linear scleroderma on her left paramedian forehead and scalp and suffered from headaches and dizziness. Axial T2-weighted MRI showed a 1 cm, high intense signal abnormality in the medial aspect of the left frontal lobe.

Adolescent↗
PubMed2000

[L-arginine].

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Animals↗
PubMed2000

[Evaluation of vascular endothelial function].

Endothelial function was evaluated in renal and forearm vessels from patients with essential hypertension. First, the increase in renal blood flow evaluated by the clearance of para-aminohippurate, serum c-GMP and urinary NOx during L-arginine infusion was significantly attenuated in essential hypertension. This attenuated endothelium-dependent vasodilation was improved by angiotensin converting enzyme inhibitor, but unchanged by calcium antagonist. Second, the increase in forearm blood flow evaluated by plethysmography during acetylcholine infusion or reactive hyperemia was attenuated in essential hypertension. This attenuation was abolished by NO synthesis inhibitor. Forearm endothelial function was improved by angiotensin converting enzyme inhibitor, daily aerobic exercise and body weight reduction by low calorie diet. In conclusion, endothelium-dependent vasodilation was attenuated in renal and forearm vasculature of essential hypertensives via reduction of NO synthesis. This attenuation can be improved by several treatments.

Acetylcholine↗
PubMed1999

Regular aerobic exercise augments endothelium-dependent vascular relaxation in normotensive as well as hypertensive subjects: role of endothelium-derived nitric oxide.

BACKGROUND: Several nonpharmacological interventions, including exercise, are recommended in primary prevention of hypertension and other cardiovascular diseases in which the pathogenetic role of endothelial dysfunction has been suggested. We studied the effects of long-term aerobic exercise on endothelial function in patients with essential hypertension. METHODS AND RESULTS: The forearm blood flow was measured by strain-gauge plethysmography. The responses of forearm vasculature to acetylcholine were smaller in the hypertensive patients than in the normotensive subjects. There was no significant difference in forearm vascular responses to isosorbide dinitrate in the normotensive and hypertensive subjects. We evaluated the effects of physical exercise for 12 weeks on forearm hemodynamics in untreated patients with mild essential hypertension who were divided randomly into an exercise group (n=10) and a control group (n=7). After 12 weeks, the forearm blood flow response to acetylcholine increased significantly, from 25.8+/-9.8 to 32.3+/-11.2 mL. min(-1). 100 mL tissue(-1) (P<0.05), in the exercise group but not in the control group. The increase in the forearm blood flow after isosorbide dinitrate was similar before and after 12 weeks of follow-up in both groups. The infusion of N(G)-monomethyl-L-arginine abolished the exercise-induced enhancement of forearm vasorelaxation evoked by acetylcholine in the exercising group. In normotensive subjects also, long-term aerobic exercise augmented acetylcholine-stimulated nitric oxide release. CONCLUSIONS: These findings suggest that long-term physical exercise improves endothelium-dependent vasorelaxation through an increase in the release of nitric oxide in normotensive as well as hypertensive subjects.

Acetylcholine↗
PubMed1999

Presence of phospholipid-neutral lipid complex structures in atherosclerotic lesions as detected by a novel monoclonal antibody.

A novel monoclonal antibody (ASH1a/256C) that recognizes atherosclerotic lesions in human and Watanabe heritable hyperlipidemic (WHHL) rabbit aortae is described. When (123)I-labeled ASH1a/256C antibody is injected intravenously into WHHL rabbits, it associates specifically with fatty streaks on the aorta. The antigen recognized by the antibody is lipid, based on extraction with chloroform and methanol from WHHL rabbit tissues. The antigen, purified by high performance liquid chromatography, was shown to be phosphatidylcholine (PC), which contains unsaturated fatty acyl groups based on analyses utilizing (1)H and (13)C nuclear magnetic resonance, Fourier transfer-infrared spectrum, and mass spectrometry. The antibody did not react with other classes of phospholipids or neutral lipids when tested using an enzyme-linked immunosorbent assay. When PC was mixed with either cholesterol, cholesteryl ester, or triacylglycerol, however, the reactivity of the antibody to PC increased up to 8-fold. Homogenates of aorta tissue obtained from normal and WHHL rabbits were fractionated using sucrose density gradient ultracentrifugation in which neutral lipid droplets, cellular membranes, and proteins are separated. The phospholipid content in cellular membrane fractions from WHHL rabbits was twice as high as that of normal rabbits, and there was an enormous difference in the antigenic activity in these fractions. The content of cholesterol in the cellular membrane fraction of WHHL rabbits was approximately 50 times higher than that of normal rabbits. Addition of neutral lipids to the cellular membrane fraction of normal rabbit markedly increased the antigenic activity. Atheromatous lesions in thickened WHHL rabbit aortic intima that were rich in lipid droplets were stained positively with ASH1a/256C immunohistochemically. These results strongly suggest that PC-neutral lipid complex domains are formed in atherosclerotic lesions.

Animals↗
PubMed1999

Age-related decrease in brain-derived neurotrophic factor gene expression in the brain of the zitter rat with genetic spongiform encephalopathy.

The zitter rat exhibits a progressive degradation in neuronal cells and genetic spongiform encephalopathy with age. In order to elucidate the involvement of the expression of the neurotrophic factor in neuropathology of the rat, we quantified mRNA levels of neurotrophic factors (nerve growth factor, brain-derived neurotrophic factor (BDNF), and neurotrophin-3, ciliary neurotrophic factor and glial-cell-line-derived neurotrophic factor) in the zitter rat brain. Expression of the BDNF gene was lower in the zitter rat brain (cerebrum, cerebellum, and brainstem regions). Interestingly, kinase activity of mitogen activated protein kinase (MAPK) Erk2 involved in the expression of BDNF was also down regulated, despite an unchanging expression of MAPK protein. These results show the possible involvement of a MAPK pathway in BDNF mRNA reduction in the zitter rat brain.

Aging↗
PubMed1999

Loss of wild-type carrier-mediated L-carnitine transport activity in hepatocytes of juvenile visceral steatosis mice.

Juvenile visceral steatosis (JVS) mice, which show systemic L-carnitine deficiency, may be an animal model of Reye's syndrome because of its phenotype of fat deposition and mitochondrial abnormalities in the liver. In this study, we compared the characteristics of the L-carnitine transport in isolated hepatocytes from wild-type and JVS mice. The uptake of L-carnitine by wild-type hepatocytes was saturable and the Eadie-Hofstee plot showed 2 distinct components. The apparent Michaelis constant (K(m)) and the maximum transport rate (V(max)) were 4.6 micromol/L and 59.5 pmol/15 min/10(6) cells, respectively, for the high-affinity component, and 404 micromol/L and 713 pmol/15 min/10(6) cells, respectively, for the low-affinity component. The high-affinity L-carnitine uptake occurred via an active carrier-mediated transport mechanism, which is characterized by Na(+)-, energy-, and pH-dependency. On the other hand, the high-affinity uptake was absent in JVS hepatocytes, and the values of K(m) and V(max) for the low-affinity uptake were 475 micromol/L and 557 pmol/15 min/10(6) cells, respectively. The hepatic carnitine transport properties in wild-type hepatocytes were similar to those of high-affinity mouse Octn2-transfected HEK293 cells. This study suggests that Octn2-type carnitine transporter is dysfunctional in hepatocytes of JVS mice.

2,4-Dinitrophenol↗
PubMed1999

Effect of L-arginine infusion on systemic and renal hemodynamics in hypertensive patients.

This study was designed to compare the renal endothelial function in patients with essential hypertension and normal renal function with that in hypertensive patients with renal insufficiency. We studied the effects of L-arginine (500 mg/kg intravenously over 30 min) on renal hemodynamics in 30 normotensive control subjects, 32 patients with mild to moderate essential hypertension who had normal renal function, and seven hypertensive patients with renal insufficiency who had a serum creatinine concentration >2.0 mg/mL and a glomerular filtration rate <50 mL/min/1.48 m2. L-Arginine infusion similarly reduced the mean blood pressure between the three groups (normotensive: -9.7% +/- 0.7%, hypertensives with normal renal function: -10.2% +/- 0.8%, and hypertensives with renal insufficiency: -8.2% +/- 1.3%). The L-arginine-induced decrease in renal vascular resistance was smaller in essential hypertensive patients than in normotensive subjects (-11.0% +/- 2.2 v -19.8% +/- 2.1%, P <.05). However, L-arginine had no effect on the renal vascular resistance in hypertensive patients with renal insufficiency (1.6% +/- 4.8%). Urine nitrite/nitrate levels in response to L-arginine significantly increased in the three groups in the following order: patients with renal insufficiency (47% +/- 15%), essential hypertensive patients (87% +/- 10%), and normotensive subjects (129% +/- 12%). The glomerular filtration rate was unaffected by L-arginine in normotensive and essential hypertensive patients (3.1% +/- 2.4% and 4.2% +/- 2.5%), but significantly decreased in hypertensive patients with renal insufficiency (-13.7% +/- 6.1%). These findings suggest that the ability of the L-arginine-nitric oxide-cGMP pathway to relax the renal vascular tone may be impaired in essential hypertensive patients and more markedly blunted in hypertensive patients with renal insufficiency, in parallel with increasing serum creatinine concentrations.

Arginine↗
PubMed1999

A case of sarcoidosis involving the tongue.

Sarcoidosis is a systemic granulomatous disorder which commonly affects the skin. Involvement of the tongue is rare; a review of the previous literature over the last 30 years revealed only six cases of sarcoidosis affecting the tongue. We studied a case of sarcoidosis involving the tongue in a 32-year-old Japanese woman with characteristic clinical and pathological findings. She visited our department with a complaint of a tongue lesion of which she had been aware for a month. A diagnosis of sarcoidosis was made for the lesion by clinical and pathological examinations. Oral involvement by sarcoidosis is rare, however this disorder should be considered as a possible cause of intraoral granulomatous lesions.

Adrenal Cortex Hormones↗
PubMed1999

Identification of CtBP1 and CtBP2 as corepressors of zinc finger-homeodomain factor deltaEF1.

deltaEF1, a representative of the zinc finger-homeodomain protein family, is a transcriptional repressor which binds E2-box (CACCTG) and related sequences and counteracts the activators through transrepression mechanisms. It has been shown that the N-proximal region of the protein is involved in the transrepression. Here we demonstrate that deltaEF1 has a second mechanism of transrepression recruiting CtBP1 or CtBP2 as its corepressor. A two-hybrid screen of mouse cDNAs with various portions of deltaEF1 identified these proteins, which bind to deltaEF1 in a manner dependent on the PLDLSL sequence located in the short medial (MS) portion of deltaEF1. CtBP1 is the mouse orthologue of human CtBP, known as the C-terminal binding protein of adenovirus E1A, while CtBP2 is the second homologue. Fusion of mouse CtBP1 or CtBP2 to Gal4DBD (Gal4 DNA binding domain) made them Gal4 binding site-dependent transcriptional repressors in transfected 10T1/2 cells, indicating their involvement in a transcriptional repression mechanism. When the MS portion of deltaEF1 was used to Gal4DBD and used to transfect cells, a strong transrepression activity was generated, but this activity was totally dependent on the PLDLSL sequence which served as the site for interaction with endogenous CtBP proteins, indicating that CtBP1 and -2 can act as corepressors. Exogenous CtBP1/2 significantly enhanced transcriptional repression by deltaEF1, and this enhancement was lost if the PLDLSL sequence was altered, demonstrating that CtBP1 and -2 act as corepressors of deltaEF1. In the mouse, CtBP1 is expressed from embryo to adult, but CtBP2 is mainly expressed during embryogenesis. In developing embryos, CtBP1 and CtBP2 are expressed broadly with different tissue preferences. Remarkably, their high expression occurs in subsets of deltaEF1-expressing tissues, e.g., cephalic and dorsal root ganglia, spinal cord, posterior-distal halves of the limb bud mesenchyme, and perichondrium of forming digits, supporting the conclusion that CtBP1 and -2 play crucial roles in the repressor action of deltaEF1 in these tissues.

Alcohol Oxidoreductases↗
PubMed1999

Daily aerobic exercise improves reactive hyperemia in patients with essential hypertension.

The effects of long-term aerobic exercise on endothelial function in patients with essential hypertension remain unclear. To determine whether endothelial function relating to forearm hemodynamics in these patients differs from normotensive subjects and whether endothelial function can be modified by continued physical exercise, we randomized patients with essential hypertension into a group that engaged in 30 minutes of brisk walking 5 to 7 times weekly for 12 weeks (n=20) or a group that underwent no activity modifications (control group, n=7). Forearm blood flow was measured using strain-gauge plethysmography during reactive hyperemia to test for endothelium-dependent vasodilation and after sublingual nitroglycerin administration to test endothelium-independent vasodilation. Forearm blood flow in hypertensive patients during reactive hyperemia was significantly less than that in normotensive subjects (n=17). Increases in forearm blood flow after nitroglycerin were similar between hypertensive and normotensive subjects. Exercise lowered mean blood pressure from 115.7+/-5.3 to 110.2+/-5.1 mm Hg (P<0.01) and forearm vascular resistance from 25.6+/-3.2 to 23. 2+/-2.8 mm Hg/mL per minute per 100 mL tissue (P<0.01); no change occurred in controls. Basal forearm blood flow, body weight, and heart rate did not differ with exercise. After 12 weeks of exercise, maximal forearm blood flow response during reactive hyperemia increased significantly, from 38.4+/-4.6 to 47.1+/-4.9 mL/min per 100 mL tissue (P<0.05); this increase was not seen in controls. Changes in forearm blood flow after sublingual nitroglycerin administration were similar before and after 12 weeks of exercise. Intra-arterial infusion of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine abolished the enhancement of reactive hyperemia induced by 12 weeks of exercise. These findings suggest that through increased release of nitric oxide, continued physical exercise alleviates impairment of reactive hyperemia in patients with essential hypertension.

Analysis of Variance↗
PubMed1999

Characteristics of L-carnitine transport in cultured human hepatoma HLF cells.

The recently cloned organic cation transporter, OCTN2, isolated as a homologue of OCTN1, has been shown to be of physiological importance in the renal tubular reabsorption of filtered L-carnitine as a high-affinity Na+ carnitine transporter in man. Although the mutation of the OCTN2 gene has been proved to be directly related to primary carnitine deficiency, there is little information about the L-carnitine transport system in the liver. In this study, the characteristics of L-carnitine transport into hepatocytes were studied by use of cultured human hepatoma HLF cells, which expressed OCTN2 mRNA to a greater extent than OCTN1 mRNA. The uptake of L-carnitine into HLF cells was saturable and the Eadie-Hofstee plot showed two distinct components. The apparent Michaelis constant and the maximum transport rate were 6.59+/-1.85 microM (mean+/-s.d.) and 78.5+/-21.4 pmol/5 min/10(6) cells, respectively, for high-affinity uptake, and 590+/-134 microM and 1507+/-142 pmol/5 min/10(6) cells, respectively, for low-affinity uptake. The high affinity L-carnitine transporter was significantly inhibited by metabolic inhibitors (sodium azide, dinitrophenol, iodoacetic acid) and at low temperature (4 degrees C). Uptake of [3H]L-carnitine also required the presence of Na+ ions in the external medium. The uptake activity was highest at pH 7.4, and was significantly lower at acidic or basic pH. L-Carnitine analogues (D-carnitine, L-acetylcarnitine and gamma-butyrobetaine) strongly inhibited uptake of [3H] L-carnitine, whereas beta-alanine, glycine, choline, acetylcholine and an organic anion and cation had little or no inhibitory effect. In conclusion, L-carnitine is absorbed by hepatocytes from man by an active carrier-mediated transport system which is Na+-, energy- and pH-dependent and has properties very similar to those of the carnitine transporter OCTN2.

Biological Transport, Active↗
PubMed1999

Decreased tissue distribution of L-carnitine in juvenile visceral steatosis mice.

We kinetically analyzed the disposition of L-carnitine of juvenile visceral steatosis (JVS) mice compared with that of normal mice to elucidate the mechanism of the systemic L-carnitine deficiency of JVS mice. There were significant differences in the plasma concentration-time course of total radioactive carnitine (L-[3H]carnitine, [acetyl-3H]carnitine, and other [acyl-3H]carnitines) between normal and JVS mice after a single i.v. or p.o. administration of L-[3H]carnitine (250 ng/kg). The oral bioavailability of L-[3H]carnitine in JVS mice (0.341) was about half of that in normal mice (0.675). The cumulative urinary excretion of total radioactive carnitine in JVS mice was about 10-fold more than that in normal mice, and the total clearance of unchanged L-[3H]carnitine for JVS mice (6.70 ml/min) was significantly higher than that for normal mice (2.45 ml/min). The distribution volume at the steady state of unchanged L-[3H]carnitine in JVS mice (1.10 liters/kg) was significantly smaller than that in normal mice (8.16 liters/kg). At 4 h after an i.v. administration, the apparent tissue-to-plasma concentration ratios of unchanged L-[3H]carnitine for various tissues of JVS mice, except for brain, were about one half to one 20th of those in normal mice. In conclusion, this in vivo disposition kinetic study of L-carnitine supports the previous in vitro finding that the L-carnitine transporter is absent or functionally deficient in JVS mice because the renal reabsorption, the intestinal absorption, and the apparent tissue-to-plasma concentration ratios in JVS mice are significantly lower than those in normal mice. The JVS mouse should be a useful experimental model for studying carnitine deficiency diseases.

Animals↗