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Biomedical subjects

H Sone

Publications and source records attributed to H Sone.

At least 73 records · Page 4Linked to original sources

Effects of high glucose concentration and a thromboxane synthase inhibitor on the production of thromboxane A2 and prostaglandin I2 and E2 by retinal endothelial cells.

To clarify the involvement of the prostaglandin (PG)-thromboxane (TX) system in diabetic retinopathy, the production of thromboxane A2 (TXA2), prostaglandin I2 (PGI2) and prostaglandin E2 (PGE2) and the effects of a thromboxane synthase inhibitor (TXSI; KDI-792; 5Z-6[(2S,4R)-4-(4-chlorophenylsulfonylamino)-1-(3-pyridyl methyl)-2 pyrrolidinyl]-5-hexenoic acid hydrochloride) were examined under high glucose concentration using bovine retinal endothelial cells. TXB2 was used as an index of TXA2, and 6-keto-PGF1 alpha as an index of PGI2. The levels of TXA2 and PGI2 were 182.3 +/- 34.3 pg/mg and 336.7 +/- 36.1 pg/mg protein at 5.5 mM of glucose, and both increased linearly with the glucose concentration to reach 430.1 +/_ 29.7 pg/mg and 511.4 +/- 65.8 pg/mg protein at 33 mM glucose (mean +/- SD, P<0.01). Neither TXA2 nor PGI2 changed significantly under elevated osmolarity. The production of PGE2 was affected only slightly by high glucose concentrations or by TXSI. Normalization of the PGI2/TXA2 ratio by TXSI at high glucose concentrations was marked.

Animals↗

Progesterone induces vascular endothelial growth factor on retinal pigment epithelial cells in culture.

Diabetic retinopathy is known to frequently deteriorate during pregnancy but the cause remains obscure. Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), is a potent vascular endothelial cell mitogen which is mainly up-regulated by hypoxia, and is closely associated with the development and progression of diabetic retinopathy. To examine the influence of the drastic hormonal alterations during pregnancy on the worsening of diabetic retinopathy, we examined the effects of estradiol (E2) and progesterone (P4) on the production of VEGF/VPF in bovine retinal pigment epithelial cells in culture. The VEGF/VPF production was significantly elevated (214.5 +/- 28.3 ng/g protein, P < 0.01) by 48 h of exposure to a high concentration of P4(10 microM), which is still within the physiological range during pregnancy, compared to that of the control group (147.7 +/- 17.9 ng/g protein). However, E2 significantly stimulated the production of VEGF/VPF only at concentrations (100 microM) much higher than normally encountered during pregnancy. These two hormones were not observed to have a synergistic effect, at least at physiological concentrations. As the increase in serum P4 levels during pregnancy is reported to be greater in pregnant diabetic patients with progressive retinopathy, our findings suggest that P4 may contribute to the worsening of diabetic retinopathy during pregnancy by up-regulating intraocular VEGF levels.

Animals↗

Acute effect of beraprost sodium on lower limb circulation in patients with non-insulin-dependent diabetes mellitus-evaluation by color Doppler ultrasonography and laser cutaneous blood flowmetry.

The acute effects of beraprost sodium (sodium (+/-)-(1R*, 2R, 3aS*, 8bS*)-2, 3, 3a 8b-tetrahydro-2-hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-I- octen-6-ynyl] -1H-cyclopenta [b] bensofuran-5-butyrate), a stable analogue of prostaglandin I2 which works as a vasodilator and anti-platelet agent, were investigated in patients with non-insulin dependent diabetes mellitus. Its effects on the dorsal pedis artery were examined using a new real-time two-dimensional Doppler ultrasonographic technique and by laser blood flowmetry. Before and 60 min after oral administration of beraprost sodium (Dolner 40 micrograms) and elastase (Elaszym 1800 U), the cross-sectional area (CSA) of the dorsal pedis artery and its blood flow index (BFI), calculated from the maximum flow velocity and area, were determined. Dermal microcirculatory blood volume (MBV) was also measured by laser blood flowmetry. In the beraprost sodium group, the CSA, BFI and MBV were significantly increased, while in the elastase group, no significant changes were observed. These result suggest that beraprost sodium has a beneficial effect on diabetic macro- and microangiopathy.

Arteries↗

Predicting long-term glycemic control of post-educational type II diabetic patients by evaluating serum 1,5-anhydroglucitol levels.

1,5-Anhydroglucitol (1.5-AG) is known to closely reflect diabetic control within several days. The possibility of predicting long-term glycemic control after an educational hospitalization of type II diabetic patients was investigated by examining the relationship between changes in serum 1,5-AG levels after a short-term trial home stay following an educational program and long-term changes in glycosylated hemoglobin A1c (HbA1c) levels after discharge. After 22 patients with type II diabetes had successfully completed the educational hospitalization program, they returned as outpatients for 5 nights in a row. Changes in serum 1,5-AG levels were determined during this period. The HbA1c levels were then determined over a period of 3 months after discharge, and the relationship between changes in 1,5-AG and HbA1c levels was examined. Changes in serum 1,5-AG levels during the 5-day trial home stay and the changes in HbA1c levels during the 3 months after discharge from the hospital were found to be significantly correlated (r = 0.70, P < 0.01). A comparison of the decreased group, which exhibited a decrease in 1.5-AG levels of 5.0 mumol/l or more during the trial home stay, and the unchanged group, revealed that increases in body mass index 3 months after discharge were significantly higher in the decreased group (1.2 +/- 0.4%) than in the unchanged group (0.2 +/- 0.5%) (P < 0.05). Determination of serum 1,5-AG levels of patients with type II diabetes before and after a trial home stay following educational hospitalization was found to be useful in identifying patients at high risk of recurrence of poor glycemic control in the future.

Aged↗

Hepatocellular carcinoma induction in LEC rats by a low dose of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline.

A food-borne heterocyclic amine, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), induces hepatocellular carcinomas (HCCs) in F344 male rats at an incidence of 95%, when fed in the diet at 400 ppm for 61 weeks. In this study, the effect of a low dose of MeIQx was examined in Long-Evans with cinnamon-like coat color (LEC) rats, which have a mutation in Atp7b and suffer from hereditary hepatitis and HCCs, with high levels of copper accumulation in the liver. Rats of the LEC and Long-Evans with agouti coat color (LEA) sibling lines were given a diet containing 40 ppm MeIQx from the age of 23 weeks to 63 weeks, for a total administration period of 40 weeks. In LEC rats, HCCs were observed in 8/8 animals administered MeIQx, and 2/8 rats receiving a normal diet. The number of HCCs per rat (mean +/- SD) was 2.8 +/- 2.0 and 0.3 +/- 0.5, respectively. In the LEA rats, however, no tumors were induced by administration of MeIQx. These results indicate that damaged liver associated with compensatory cell proliferation is much more susceptible to chemical hepatocarcinogens, including MeIQx, than the normal liver.

Alanine Transaminase↗

Radioiodinated metaiodobenzylguanidine scintigraphy for pheochromocytoma. A false-positive case of adrenocortical adenoma and literature review.

Radioiodinated metaiodobenzylguanidine (MIBG) scintigraphy is known for its high specificity in detecting pheochromocytoma and other tumors of neural crest origin. We describe herein the first case of a definite adrenocortical adenoma that demonstrated false-positive uptake on MIBG scintigraphy. In addition, we reviewed all 13 reported cases showing false-positive uptake, and suggest that careful evaluation is needed before diagnosing a 'silent' or 'asymptomatic' pheochromocytoma.

3-Iodobenzylguanidine↗

Restoration of myo-inositol uptake by eicosapentaenoic acid in human skin fibroblasts cultured in high-glucose medium.

The effects of elevated glucose and eicosapentaenoic acid (EPA, C20:5 omega 3) on myo-inositol uptake in human skin fibroblasts (HSF) were evaluated. Myo-inositol incorporation into HSF was dependent on an active transport system via Na(+)-K+ ATPase activity based on the results with Na+ deprivation and ouabain (5 mM). Although glucose (27.5, 55 mM) inhibited 2-[3H] myo-inositol uptake, the addition of EPA (3 x 10(-4) M) prevented glucose-mediated inhibition. Since EPA decreased glucose-mediated inhibition of myo-inositol uptake, this agent might ameliorate some of the devastating functions associated with diabetes.

Cells, Cultured↗

The effect of nilvadipine on bloodflow in the dorsal pedis artery in type 2 diabetic patients--a study using duplex Doppler ultrasonography.

The effects of nilvadipine on the peripheral circulation in the lower extremities using a duplex system of two-dimensional colour and pulse Doppler ultrasonography were studied in 32 patients with type 2 diabetes mellitus and mild essential hypertension. The patients (19 men and 13 women) were randomly divided into treatment and control groups. The anatomical cross-sectional area and blood flow index of the dorsal pedis artery were determined by colour and pulse Doppler ultrasonography before and 60 min after administration of 4 mg nilvadipine or placebo. Pulse rate and blood pressure were measured simultaneously. There were no significant changes in pulse rate or blood pressure after administration of either drug. Both cross-sectional areas (from 4.3 +/- 0.4 to 5.2 +/- 0.5 mm2, p < 0.05) and blood flow index (from 40.3 +/- 4.3 to 58.8 +/- 9.0, p < 0.05) were significantly increased in the treatment group, whereas there were no significant changes in either measurement in the control group. The findings showed that a single administration of nilvadipine increases blood flow in the dorsal pedis arteries of diabetic patients.

Arteries↗

Transient nephrogenic diabetes insipidus accompanied by possible psychogenic polydipsia.

A 50-year-old Japanese man had been suffering from polydipsia and polyuria for 2 months without any other specific symptoms. His daily urinary output reached 5 liters. On admission, no abnormalities of the kidneys, heart, thyroid, adrenals, pituitary or hypothalamus were detected by laboratory tests and MRI of the head. Pure psychogenic polydipsia was ruled out because his urine volume did not decrease sufficiently with 18 h of water deprivation and the subsequent injection of aqueous vasopressin. Plasma arginine vasopressin (AVP) levels against plasma osmolality remained within the normal range during the test. These results indicated that diabetes insipidus in this case was caused by renal insensitivity to AVP. The symptoms disappeared spontaneously, and marked improvement was observed in a second water deprivation test 1 month later, although the maximum urine concentration was still subnormal. The combination of both latent insufficiency of AVP secretion and impairment of the renal countercurrent system induced by psychogenic polydipsia was speculated as a possible mechanism for the transient nephrogenic diabetes insipidus in this case.

Arginine Vasopressin↗

Efficacy of Ibudilast on lower limb circulation of diabetic patients with minimally impaired baseline flow: a study using color Doppler ultrasonography and laser Doppler flowmetry.

Ibudilast is a prostacyclin-mediated vasodilator and antiplatelet agent. The hemodynamic effects of ibudilast were evaluated in 41 patients with non-insulin-dependent diabetes mellitus by means of two-dimensional Doppler ultrasonography and laser Doppler blood flowmetry. Before and one hour after oral administration of ibudilast (10 mg), or elastase (1800 U) as a control, the cross-sectional area (CSA) of the dorsal pedis artery, its blood flow index (BFI), and dermal microcirculatory blood volume (MBV) were measured. In the ibudilast group, all of the parameters (CSA, BFI, and MBV) significantly increased as compared with the elastase group. These data suggest that ibudilast is effective in ameliorating diabetic macroangiopathy and microangiopathy of the lower limbs.

Administration, Oral↗

[A case of Shy-Drager syndrome complicated with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and incomplete paralysis of bilateral vocal cords].

A 67-year-old man with SIADH complicated by slowly progressing autonomic failure was described. The patient noticed constipation at the age of 57. In the following years, he suffered from urinary incontinence, depletion of sweating, impotence, sleeplessness with snore, and dizziness while walking. Physical examination revealed a masked oily face with slight cerebellar disturbance. Abnormality of autonomic function tests was recognized and he was diagnosed as Shy-Drager syndrome with gradually progressing, diffuse autonomic failure accompanied by slight cerebellar ataxia and Parkinsonism. Both serum sodium level and plasma osmotic pressure were reduced, whereas daily sodium excretion was more than 100mEq and urinary osmolality was about 500mOsm/kgH2O. His renal function was intact, and the adrenocortical and thyroid hormone levels were normal, then criteria of SIADH was fulfilled. SIADH was thought to have occurred on the basis of Shy-Drager syndrome. Water load test showed failure of adequate water diuresis, but intravenous phenytoin administration following the water load test ameliorated the diuresis to normal. The relationship between plasma osmolality and the ADH response indicates that ADH was adequately secreted in response to the increase in plasma osmolality but not suppressed in response to the decrease in plasma osmolality below 280mOsm/kgH2O. These results suggest that ADH synthesis in the hypothalamus and its secretion from the pituitary gland were both intact. The response of ADH secretion to the orthostatic hypotension induced by head-up tilt was quite blunted, being compatible with Shy-Drager Syndrome. Sleep disturbance was studied by polysomnography and laryngoscopy, and was revealed to be based upon severe sleep apnea due to incomplete paralysis of the bilateral vocal cords. Sleep apnea due to vocal cord paralysis is sometimes found to be complicated in patients with multiple system atrophy (MSA) including Shy-Drager syndrome, and is known as Gerhardt syndrome. This is the first report on a case of Shy-Drager syndrome complicated with SIADH and bilateral vocal cord paralysis. In this case, SIADH is caused by impaired afferent pathways from baroreceptors to the hypothalamus, which transfer inhibitory stimuli on ADH secretion. It is suggested that Shy-Drager syndrome should be considered one of the causes of SIADH.

Aged↗

Identification of cis- and trans-acting elements involved in the expression of cold shock-inducible TIP1 gene of yeast Saccharomyces cerevisiae.

Northern blot hybridization analysis of a series of 5' end, 3' end and internal deletions has revealed that at least four different regions are involved in the regulation of the expression of TIP1, a cold shock-inducible gene of Saccharomyces cerevisiae. One of these four regions has negative effect on the expression of the TIP1 gene, while the others are responsible for the activation and cold shock-induction of the gene. A fragment involved in the cold-shock induction of TIP1 was used as a probe in gel retardation assays to identify the cold shock-factor. The cold shock-factor could be detected in cells grown at 30 degrees C as well as 10 degrees C, but both the amount of the factor and its affinity to DNA were found to increase 2-3-fold after cold shock. In addition, another factor was found to bind just upstream of the cold shock element, in a region where a transcriptional activator was predicted to function by Northern blot hybridization analysis. The amount of this activating factor and its affinity for DNA was not affected by temperature. Implications of our data on possible mechanisms of transcriptional regulation of the TIP1 gene by cold shock are discussed.

Base Sequence↗

Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and Gerhardt syndrome associated with Shy-Drager syndrome.

This is the first report on a case of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with Gerhardt syndrome (paralysis of bilateral vocal cords). A 67-year-old Japanese man suffering from progressive autonomic failure was diagnosed as having Shy-Drager syndrome (SDS) with hyponatremia due to SIADH and severe sleep apnea caused by a bilateral recurrent nerve palsy. Water load test showed alteration in diuresis which was corrected by phenytoin. Arginine vasopressin secretion was not suppressed by plasma osmolality below 280 mOsm/kgH2O. Impairment of the afferent pathways of baroreceptors, or impairment of the osmoreceptors could be speculated as the etiological factor of the SIADH observed in this case.

Aged↗

[Clinical efficacy of arbekacin in patients with methicillin-resistant Staphylococcus aureus infections. Research Group of MRSA Forum].

We investigated the clinical efficacy of arbekacin (ABK) in patients with methicillin-resistant Staphylococcus aureus (MRSA) infections, and also studied coagulase types, beta-lactamase producing activity and drug sensitivity of MRSA isolated from various clinical specimens. A total of 23 patients with MRSA infections (13 cases of pneumonia, 1 case of sepsis, 1 case of pneumonia and sepsis and 8 cases of the others) who were hospitalized from April 1992 to September 1993 were enrolled in this study. They were 14 males and 9 females, and the mean age was 66.9 years (range, 18-91 years). All patients had underlying diseases (mainly malignant tumors and cerebrovascular diseases). ABK was given intravenously at doses ranging from 75 to 100 mg twice daily. The clinical efficacy rate was 90%; 8 cases showed excellent responses, 10 cases good, 1 case fair, 1 case poor and 3 cases were unevaluable. The eradication rate of MRSA was 81.8%; 16 cases were judged as eradicated, 3 cases decreased, 2 cases replaced, 1 case unchanged and in 1 case the bacteriological response was unknown. Side effects were not observed, but S-GPT was elevated in 1 case. Coagulase types of MRSA (123 strains) isolated at the institutes involved in the study were type II (56 strains), type IV (12 strains), type VII (13 strains) and other types (2 strains), but coagulase types of 40 strains could not be determined. Eighty-four strains (68.3%) produced beta-lactamases. MICs of ABK were 0.5 microgram/ml against 43 strains and 1 microgram/ml against 37 strains, and all of the MICs were under 4 micrograms/ml. In summary, ABK showed high antimicrobial activity against MRSA and clinical usefulness in the infections investigated.

Adolescent↗