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Biomedical subjects

Y Uehara

Publications and source records attributed to Y Uehara.

At least 109 records · Page 6Linked to original sources
PubMed1996

Angelmicin B, a new inhibitor of oncogenic signal transduction, inhibits growth and induces myelomonocytic differentiation of human myeloid leukemia HL-60 cells.

Angelmicin B is a new microbial substance which inhibits src tyrosine kinase activity and oncogenic signal transduction. We investigated the effect of angelmicin B on the proliferation and differentiation of the HL-60 human myeloid leukemia cell line. Angelmicin B caused the dose-dependent inhibition of cell proliferation and induction of differentiation along the myelomonocytic pathway, as determined by morphological changes, nitroblue tetrazolium (NBT) reduction, and non-specific esterase and lysozyme activities at concentrations ranging from 0.1 to 0.5 microgram/ml. Also, it induced significantly the differentiation of mouse myeloid leukemia M1 cells. A similar concentration of angelmicin B inhibited the growth of the myeloid leukemia cell lines K562, HEL, KU812, ML-1, U937 and THP-1, but did not induce differentiation of these cells significantly. The differentiation of HL-60 cells was enhanced by combined treatment with angelmicin B and 1 alpha, 25-dihydroxyvitamin D3 (VD3), retinoic acid or tumor necrosis factor-alpha (TNF alpha). Angelmicin analogs (A1, A2, B, C and D) had almost equivalent effects on the differentiation of HL-60 cells, although angelmicins C and D inhibited src tyrosine kinase activity less than the other analogs. The effective concentrations of angelmicin B in src kinase inactivation was about 100-fold higher than those required for the growth inhibition and differentiation induction. These findings indicate that the differentiation-inducing activity of angelmicins is not associated with their src kinase-inhibiting activity, and may be associated with the modulation of other signal pathway(s).

Animals↗
PubMed1996

Hachimi-jio-gan extract protects the kidney from hypertensive injury in Dahl salt-sensitive rat.

We investigated whether the Chinese herbal remedy, Hachimi-jio-gan extract, attenuates the renal injury seen in salt-induced hypertension in Dahl salt-sensitive (Dahl S) rats. Administration of this extract for 5 weeks dose-dependently decreased systolic blood pressure in Dahl S rats fed with a high-salt (2% NaCl) diet. This blood pressure reduction was associated with a decrease in cardiac mass and in thickness of the aortic wall. Urinary excretion of prostaglandin E2 was increased and glomerular filtration rate was improved with this treatment. Glomerulosclerosis and arterial injury in the kidney were morphologically improved. These data suggest that Hachimi-jio-gan extract exhibits an antihypertensive effect, which is associated with partial resolution of renal injury in salt-induced hypertension.

Animals↗
PubMed1996

Ouabainlike compound in hypertension associated with ectopic corticotropin syndrome.

Molecular mechanisms related to sodium retention have been implicated in the pathogenesis of hypertension. It is unclear how sodium retention leads to a rise in blood pressure, but ouabainlike compound may act as a final common pathway in sodium-induced hypertension. In ectopic corticotropin syndrome, hypertension has been attributed to cortisol inactivation overload, giving rise to mineralocorticoid-type hypertension. We sequentially measured plasma and urinary levels of ouabainlike compound over 2 months to evaluate its role in the hypertensive mechanisms in a 64-year-old man with this syndrome caused by lung cancer. His data included hypokalemia and increased cortisol concentrations, corticotropin levels, and urinary 17-hydroxycorticosteroid excretion. Plasma renin activity was suppressed. Plasma and urinary levels of ouabainlike compound were markedly increased concomitantly with high blood pressure. The maximum plasma level was 40-fold the normal range of the subject. After chemotherapy, ouabainlike compound levels gradually decreased in parallel with the decline in blood pressure and rise in potassium concentration. A correlation was observed between plasma and urinary levels of ouabainlike compound (P < .05). Plasma and urinary levels of ouabainlike compound correlated with systolic (P < .01) and diastolic (P < .05) pressures, respectively. The peak of ouabainlike compound in plasma and urine coincided with that of authentic ouabain on high-performance liquid chromatography. Ouabainlike compound derived from urine inhibited [3H]ouabain binding to human erythrocytes. These findings suggest that ouabainlike compound with biological activity could partly account for hypertension in ectopic corticotropin syndrome.

ACTH Syndrome, Ectopic↗
PubMed1996

Restoration of endothelial cell function by chronic cicletanine treatment in Dahl salt-sensitive rats with salt-induced hypertension.

The effects of chronic cicletanine (CICL) treatment on endothelial cell function were investigated in Dahl salt-sensitive (Dahl S) rats. Forty-four six-week-old Dahl S rats were divided into four groups: i) 10 Dahl S rats fed a low-salt (0.3% NaCl) diet and given vehicle, ii) 12 Dahl S rats fed a high-salt (4% NaCl) diet and given vehicle, iii) 11 low-dose (10 mg/kg body weight/d) CICL-treated Dahl S rats fed a high-salt diet, and iv) 11 high-dose (30 mg/kg body weight/d) CICL-treated Dahl S rats fed a high-salt diet. The rats were maintained on the respective salt regimen for 12 wk and treated with cicletanine for the last 6 wk, after which various parameters of endothelial cell function were determined. Systolic blood pressure, measured by the tail-cuff method, was reduced significantly by high-dose cicletanine (223 vs. 195 mmHg, p < 0.01). Scanning electron microscopy revealed that high-dose CICL attenuated endothelial injury in the aorta of Dahl S rats. Arterial lesions in the heart and glomerulosclerosis in the kidney were significantly reduced by treatment with high-dose CICL. Moreover, prostacyclin (PGI2) and prostaglandin E2 (PGE2) generation in the aortic wall was significantly increased by 28% (p < 0.005) and by 149% (p < 0.001), respectively, by high-dose CICL. Nitric oxide (NO) generation in the aortic walls was significantly increased by high-dose CICL (0.38 vs. 15.4 pmol/cm2/30 min, p < 0.001). This effect was accompanied by a 47% increase in cGMP synthesis in the vascular walls. In contrast, the synthesis of PGI2, PGE2, and NO in the kidney slices did not differ significantly among the four experimental groups. In addition, the generation of vasodilatory substances inversely correlated with the score of vascular lesions in the heart and kidney. The results suggested that the blood pressure reduction by chronic cicletanine treatment in Dahl S rats is associated with an improvement in endothelial cell function. The increased release of vasodilatory substances from endothelial cells may contribute to the blood pressure reduction and attenuation of vascular injury observed with cicletanine treatment.

Animals↗
PubMed1996

Quantitative evaluation of the severity of mitral insufficiency in dogs by the color Doppler method.

Color flow mapping areas of mitral regurgitation jets (MRMA) and aortic forward flow mapping area (AFMA) were measured in 33 dogs for quantitative evaluation of pathological changes of mitral insufficiency, according to NYHA criteria, by the color Doppler method. The ratio of these areas (MRMA/AFMA) was calculated and the result showed a high correlation (r = 0.95) with the result of NYHA evaluation. The result of the present study, which corresponded to the NYHA findings, showed that the color Doppler method can be used for quantitative assessment of mitral insufficiency in dogs.

Animals↗
PubMed1996

Body mass index is a determinant of blood pressure in young adults with essential hypertensive parents. Health Care Programme of University of Tokyo.

We analysed blood pressure (BP) and various parameters related to glucose metabolism in 10,867 Japanese university students aged 19.22 +/- 0.01 years, and investigated the relationship between the subject's own BP and hypertension in close relatives. After 2 years we also examined a subset of these students enrolled in 1993. BP levels in subjects having hypertensive parents were normotensive, but significantly higher than those in subjects without hypertensive relatives or only with hypertensive grandparents. The close the genetic relationship was, the higher the subject's own BP levels. In subjects with hypertensive parents, the subject's own mean BP levels correlated significantly with the subject's own body mass indices. This correlation was much weaker in subjects without hypertensive relatives and those having only second degree relatives with hypertension. In addition, the BP levels in the offspring of hypertensive parents correlated with glutamyl-oxaloacetic transaminase. In the follow-up study in 1995, the correlation between BP levels and body mass index (BMI) was observed in this subgroup. Moreover, the subjects with hypertensive parents tended to have a higher plasma insulin level than those without hypertensive relatives. It is suggested that BP is more likely to be determined by BMI in the individuals with a genetic predisposition to hypertension.

Adult↗
PubMed1996

[Pharmacokinetic and clinical studies on azithromycin in children].

Azithromycin (AZM) is a new oral macrolide antibiotic drug. AZM either in 10% fine granules form or in 100 mg capsule form was studied for its pharmacokinetics and treatment efficacy in pediatric patients with various infections. 1. Pharmacokinetics. Plasma and urine samples were collected from four patients with pharyngitis and post-dosing drug levels were determined. The drug was given once daily at 10 mg/kg body weight for 3 days. The drug concentrations found in plasma at 96 hours after the first dosing (48 hours after the final dosing) lay in a range of 0.02 and 0.04 microgram/ml and in urine at 120 hours after the first dosing (72 hours after the final dosing) in a range between 3.2 and 7.7 micrograms/ml. AZM was found in two patients but no effect was observed on blood levels of theophylline determined between 48 and 96 hours after the first dosing in the treatment of underlying bronchial asthma. 2. Clinical study results. Clinical studies of AZM was carried out in 25 pediatric patients with bacterial infections that mainly affected the respiratory tract. The patients received either 10% fine granules at 10 or 20 mg/ kg body weight or 100 mg capsules at 10 mg/kg body weight once daily over 3 to 6 days. The drug was found markedly effective in six patients, moderately effective in thirteen patients, while the investigators could not assess the drug efficacy in six patients. Although no side effect was reported in the study, two patients experienced slight decrease in WBC.

Adolescent↗
PubMed1995

A microplate assay for quantitation of anchorage-independent growth of transformed cells.

We developed a 96-well microplate assay to quantitate anchorage-independent growth of transformed cells. Wells of tissue culture microtiter plates are coated with poly(2-hydroxyethyl methacrylate) (poly-(HEMA)) to prevent cell attachment, and cells suspended in liquid media are seeded into the treated plates. Cell growth is assessed by tetrazolium dye reduction or by counting [3H]thymidine incorporation into DNA. There appeared to be a close correlation between growth in poly(HEMA)-coated plates and colony formation in soft agar, i.e., fibroblasts transformed by various oncogene proliferated in the coated plates, whereas their normal counterparts did not. Transformed cells on the nonadhesive surface were round and formed multicellular spheroids which resembled colonies in soft agar. Cells carrying either temperature-sensitive v-src or inducible v-Ki-ras oncogene proliferated on poly(HEMA)-coated plates only when they displayed transformed phenotype. This method is simple, quick, quantitative, and economical and in many cases might be more practical than conventional soft agar colony formation assay for measurement of anchorage-independent growth.

3T3 Cells↗
PubMed1995

Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor.

Hepatocyte growth factor/scatter factor (HGF/SF) functions as a mitogen, motogen and morphogen for a variety of cultured cells. The genes for HGF/SF and its receptor (the c-met proto-oncogene product) are expressed in many tissues during the embryonic periods and in the adult. HGF/SF is thought to mediate a signal exchange between the mesenchyme and epithelia during mouse development. To examine the physiological role of HGF/SF, we generated mutant mice with a targeted disruption of the HGF/SF gene. Here we report that homozygous mutant embryos have severely impaired placentas with markedly reduced numbers of labyrinthine trophoblast cells, and die before birth. The growth of trophoblast cells was stimulated by HGF/SF in vitro, and the HGF/SF activity was released by allantois in primary culture of normal but not mutant embryos. These findings suggest that HGF/SF is an essential mediator of allantoic mesenchyme-trophoblastic epithelia interaction required for placental organogenesis.

Allantois↗
PubMed1995

The pH dependence of interleukin-1 beta effects on insulin secretion in HIT cells.

We have examined a hypothesis that the effects of recombinant human interleukin-1 beta (IL-1) on insulin secretion may depend upon the condition of intracellular pH levels in hamster clonal beta-cell line, HIT-T 15 cells. In the first experiment, the addition of 5 and 20 microM monensin, a Na+/H+ electroneutral exchange ionophore, did not attenuate a short-stimulatory effect of IL-1 on insulin secretion at 0-4 h period. At the concentration of 20 microM, monensin deleted the IL-1-induced reduction of insulin secretion at 4-24 h period, while 5 microM did not. Furthermore, 100 microM monensin blocked the bimodal effects of IL-1 on insulin secretion. In the second experiment, IL-1 significantly stimulated insulin secretion, although it did not affect cyclic AMP production at 0-4 h period. At 4-24 h period, IL-1 dose-dependently inhibited cyclic AMP production, accompanied with a significant reduction of insulin secretion. Alkalinization of circumstantial pH levels to 8.0 deleted the IL-1 effects on insulin secretion at 4-24 h period. However, alkalinization to pH 8.0 failed to attenuate the reduction of cyclic AMP production by IL-1. These data indicated that maintaining adequate intracellular pH levels may be important in the IL-1 effects on insulin secretion by the mechanism in which cyclic AMP may not be involved.

Animals↗
PubMed1995

A new adenosine subtype-1 receptor antagonist, FK-838, attenuates salt-induced hypertension in Dahl salt-sensitive rats.

We investigated the effects of the adenosine type-1 receptor antagonist FK-838 on salt-induced hypertension in Dahl-Sea salt-sensitive (Dahl S) rats. Dahl S rats fed a high-salt (4% NaCl) diet for 4 weeks were treated with FK-838 or hydrochlorothiazide for 4 weeks and alterations in kidney function and morphologic changes were assessed. FK-838 attenuated the development of hypertension in Dahl S rats, and caused a decrease in aortic weight in a dose dependent fashion. The adenosine antagonist did not produce any detectable metabolic disturbance. The blood pressure reduction by FK-838 was associated with attenuation of glomerular and arterial injury in the kidney. The renal protective effect of FK-838 treatment was associated with a reduction of plasma renin activity and plasma aldosterone concentration. In contrast, the thiazide diuretic, which produced almost the same blood pressure reduction as FK-838, did not attenuate renal damage. These data indicate that adenosine A1 receptor antagonism reduces salt-induced hypertension and the consequent renal injuries.

Animals↗
PubMed1995

Effect of high potassium diets on the vascular and renal prostaglandin system in stroke-prone spontaneously hypertensive rats.

High potassium (K) diets are known to have a protective effect on the endothelium and the kidney against hypertensive injury independent of blood pressure change. Vasodepressor prostaglandins (PGs) have been shown to be cytoprotective in various tissues. This study investigated the effect of high K diets on the vascular and renal eicosanoid system in stroke-prone spontaneously hypertensive rats (SHRsp). Eicosanoid production by the aorta and eicosanoid content in the renal cortex were examined in SHRsp rats fed high NaCl diets containing either 0.5% K (normal) or 2.1% K (high). Although the high K diet did not affect the blood pressure, SHRsp on the high K diet had less thickening of the aortic wall than SHRsp on the normal K diet (-15%, p < 0.001). The aortic strip of the high K SHRsp produced less vasodepressor PG than that of the normal K SHRsp when they were incubated in a medium (PGI2 -45%, p < 0.003; PGE2 -34%, p < 0.001). Furthermore, when the aorta was perfused in a chamber at hypertensive pressure, again the high K aorta showed reduced PGI2 production as compared with the normal K aorta (intravascular side -52%, p < 0.01). Eicosanoid content in the renal cortex was not significantly different between the normal K and the high K SHRsp (PGI2 79 vs 87 ng/g dry weight; PGE2 214 vs 233 ng/g dry weight). Thus, the high K diet reduced vascular eicosanoid production but did not alter eicosanoid content in the renal cortex. The reduced vascular eicosanoid production in the high K SHRsp may reflect the reduced necessity for cytoprotective vasodepressor PG against vascular injuries.

Administration, Oral↗
PubMed1995

Possible linkage between renal injury and cardiac remodeling in Dahl salt-sensitive rats treated with the calcium channel antagonist benidipine.

Interest in cardiovascular protection by calcium channel antagonists has grown over the past decade. We investigated the prevention of cardiac remodeling and renal injury by the long-acting calcium channel antagonist benidipine using 12 week-old Dahl salt-sensitive (Dahl S) rats fed a high-salt (4% NaCl) diet. Six-week benidipine treatment (10 mg/kg chow) decreased systolic blood pressure by 22% in Dahl S rats. This blood pressure reduction was associated with decreases in cardiac mass and weight of the aortic wall. Collagen content in the left ventricle tended to decline with benidipine treatment. In addition, glomerular filtration rate increased by 33% and arterial and glomerular lesions improved morphologically with this treatment. Regression of cardiac mass and collagen content in the left ventricle was due mainly to blood pressure reduction; however, collagen content in the low-pressure right ventricle was not only related to systemic blood pressure but to the severity of renal lesions. These data suggest that the calcium channel antagonist benidipine attenuates cardiac and renal injury in hypertensive Dahl S rats, and that part of the cardiac hypertrophy is due to a non-hemodynamic mechanism that might be responsible for, or be a consequence of, the lesions in the kidney.

Animals↗
PubMed1995

Determination of cardiac output by echocardiography.

To determine cardiac output using a non-invasive manner, we examined correlations between cardiac output values determined by ten different kinds of echocardiography and those determined by the thermodilution method. With respect to the M-mode method, one of the rotary ellipsoid approximation methods using a short axial section at the papillary muscular level, namely the GIBSON method, showed the highest correlation with the thermodilution method (r = 0.84; p < 0.01). Among the Doppler mode method, the highest correlation (r = 0.93; p < 0.01) was exhibited by the method in which the area of the luminal section of the outflow tract was accurately measured using a trace method on a short axial cross section of the tract flowing out of the left ventricle. These findings suggest that it is possible to determine cardiac output by echocardiography in the same was as with the thermodilution method. Moreover, non-invasive determination methods using echocardiography have been confirmed to be highly beneficial in clinical settings.

Animals↗
PubMed1995

Systemic amyloidosis following ankylosing spondylitis associated with congestive heart failure. A case report.

We report the case of a 38-year-old man who developed fatal, systemic amyloidosis following ankylosing spondylitis. He was admitted for symptoms of congestive heart failure. Based on parotid gland biopsy and echocardiography, he was diagnosed as having systemic amyloidosis following active ankylosing spondylitis. However, the clinical course was rapidly progressive and eventually the patient died of acute necrotizing pancreatitis. The association has been reported thus far in a limited number of cases worldwide. The literature has featured localized lesions and a benign clinical course of the amyloidosis. This case, the first report from Japan, indicates that the amyloidosis associated with ankylosing spondylitis might exhibit a rapidly progressive clinical course, thereby suggesting that in such a case, meticulous treatment is required.

Acute Disease↗