Biomedical subjects

Y Higashi

Publications and source records attributed to Y Higashi.

At least 127 records · Page 7Linked to original sources

PubMed1997

Relationship between insulin resistance and endothelium-dependent vascular relaxation in patients with essential hypertension.

The infusion of L-arginine induces the production of nitric oxide and stimulates the immediate secretion of insulin. To examine the relationship between insulin resistance and endothelium-dependent vascular relaxation in patients with essential hypertension, we evaluated the renal and insulin responses to L-arginine, 500 mg/kg infused intravenously over 30 minutes, in 23 patients with mild essential hypertension who were neither obese nor diabetic and in 20 normotensive control subjects. We found no difference between the two groups in blood glucose or insulin in the fasting condition. The renovascular relaxation induced by L-arginine was significantly less in patients with essential hypertension than in normotensive control subjects. The increase in plasma cyclic GMP in response to L-arginine was lower in hypertensive patients than in normotensive subjects. Although the serum concentrations of glucose in response to L-arginine were similar in the two groups, the serum insulin response of the essential hypertensives was significantly higher than that of the normotensive subjects. In all subjects, the peak cyclic GMP response to L-arginine was significantly correlated with the peak delta glucose/ delta insulin ratio response to L-arginine (r = .69, P < .001). Findings suggested that an impairment of endothelium-dependent renal vascular relaxation and a reduced sensitivity to insulin are present in patients with essential hypertension. A link may be present between the abnormality of the L-arginine/nitric oxide/cyclic GMP pathway and insulin resistance in patients with essential hypertension.

Arginine↗

PubMed1997

Nocturnal decline in blood pressure is attenuated by NaCl loading in salt-sensitive patients with essential hypertension: noninvasive 24-hour ambulatory blood pressure monitoring.

We investigated the effect of NaCl on the circadian blood pressure rhythm in patients with essential hypertension classified according to the presence or absence of salt sensitivity. We obtained 24-hour noninvasive ambulatory blood pressure measurements in 64 Japanese patients with mild to moderate essential hypertension who ate a low NaCl diet (50 mmol/d) for 1 week, followed by a high NaCl diet (340 mmol/d) for 1 week. Twenty-six patients whose mean blood pressure was increased more than 10% by NaCl loading were classified as salt sensitive. The remaining 38 patients were classified as salt resistant. The nocturnal decline in mean blood pressure was significantly smaller in salt-sensitive patients (8.3+/-1.0%) than in salt-resistant patients (11.5+/-0.9%) (P<.05) during a high NaCl diet but was similar in both groups during a low NaCl diet. There was no significant difference in the prevalence of the non-dipper pattern between groups on a low NaCl diet, but the prevalence of the non-dipper pattern was significantly higher in salt-sensitive patients than in salt-resistant patients on a high NaCl diet (0.57 versus 0.26, chi2=6.4; P=.02; odds ratio, 3.82). These findings suggest that the NaCl loading blunted the nocturnal decline in blood pressure in salt-sensitive patients but not in salt-resistant patients.

Blood Pressure↗

PubMed1997

Aging and severity of hypertension attenuate endothelium-dependent renal vascular relaxation in humans.

Endothelial dysfunction may be related to cardiovascular risk factors, such as aging, hypertension, and atherosclerosis. We investigated whether aging and hypertension independently alter endothelial function in the renal circulation in humans in the absence of abnormalities in lipid and glucose metabolism. L-Arginine (500 mg/kg over 30 minutes) was intravenously administered to 33 patients with essential hypertension and 35 normotensive subjects. The L-arginine-induced increases in renal plasma flow (10.1+/-0.8% versus 15.8+/-0.9%, P<.05) and plasma cGMP (53+/-4% versus 82+/-5%, P<.05) were significantly smaller in patients with essential hypertension than in the normotensive subjects. Multivariate stepwise regression analysis showed that age (P<.0002) and the mean blood pressure (P<.0001) were independently and negatively correlated with the renal plasma flow response to L-arginine. Age (P<.002), mean blood pressure (P<.0001), and male sex (P<.05) were independently correlated with the L-arginine-induced increase in plasma cGMP. The peak change in plasma cGMP was significantly correlated with the L-arginine-induced increase in renal plasma flow (r=.63, P<.001). These findings suggest that aging and hypertension may independently impair endothelium-dependent renovascular dilation and that this effect may be caused at least in part by a decrease in nitric oxide production.

Adult↗

PubMed1997

First-pass metabolism of ONO-5046 (N-[2-[4-(2,2-dimethylpropionyloxy) phenylsulfonylamino]benzoyl]aminoacetic acid), a novel elastase inhibitor, in rats.

The first-pass metabolism in the intestine and liver of ONO-5046 (N-[2-[4-(2,2-dimethylpropionyloxy)-phenylsulfonylamino]benz oyl]aminoacetic acid), a newly synthesized elastase inhibitor, was separately estimated in rats. When ONO-5046 solution was administered into the whole intestine via the bile duct at a dose of 5 mumol/rat, the extent of bioavailability was only 1.5%. A small but significant increase in the bioavailability with an increase in the dose suggested marked first-pass metabolism with a saturable process. Hepatic first-pass metabolism was estimated by determining the hepatic extraction ratio of ONO-5046 after administration into the portal vein at two different infusion rates (5 mumol/kg/9 min or 5 mumol/kg/20s). The extraction ratio was relatively small and constant (about 20%) under 2 different infusion rates of the drug. Intestinal first-pass metabolism was estimated by determining the drug recovery in the mesenteric plasma after administering the drug into the intestinal loop in situ (mesenteric blood collecting method in situ). The recovery percentage of ONO-5046 in the mesenteric plasma was small (2.58 +/- 0.04% at a dose of 1 mumol/rat), and the remaining ONO-5046 recovered in the mesenteric plasma and in the intestinal loop was a metabolite of ONO-5046 (El-601, N-[2-[(4-hydroxyphenyl)sulfonylamino]benzoyl]amino-acetic acid). Recovery percentage of ONO-5046 in the mesenteric plasma increased significantly with an increase in the dose, although the recovery percentage was still low, even at a higher dose (9.55 +/- 1.17% of dose at a dose of 5 mumol/rat). These results indicate that the low oral bioavailability of ONO-5046 in vivo is mainly due to the marked intestinal first-pass metabolism, including the metabolism in the intestinal fluid, and the dose-dependent oral bioavailability was derived from the saturable intestinal first-pass metabolism.

Animals↗

PubMed1996

Organization of the gene encoding transcriptional repressor deltaEF1 and cross-species conservation of its domains.

DeltaEF1 (delta-crystallin/E2-box factor 1) is a widely distributed repressor of transcription which binds at the E2-box sequence, CACCTG. It carries seven zinc fingers (Zf) in two clusters and a homeodomain in the middle as potential DNA-binding domains. We cloned the genomic gene encoding chicken deltaEF1 and analyzed its organization. The gene consisted of nine exons, the N-proximal Zf were encoded by exons 5 through 7, and the C-proximal Zf by exons 8 and 9. Exon 7 also coded for the large middle portion of the protein including the homeodomain. Promoter analysis and RNase-protection assay indicated that the gene is driven by a G+C-rich promoter without a TATA box, and the transcription start points (tsp) cluster around 20 bp from the start codon located in exon 1. cDNA and genomic sequences of the mouse delta EF1 were cloned and compared with the chicken sequence. The deduced amino acid (aa) sequence was highly conserved between the chicken and mouse deltaEF1, no only in DNA-binding motifs but also in other blocks (78% overall aa identity). More recently reported DNA-binding proteins, AREB6 (human) ZEB (human) and BZP (hamster), were attributed to homologues of deltaEF1, among which only AREB6 represented full-length sequence. It was also indicated that rodent deltaEF1 lacked exon 3.

Amino Acid Sequence↗

PubMed1996

Fine Needle Aspiration Cytology of Argyrophilic Mucinous Carcinoma of the Male Breast.

The results of fine needle aspiration (FNA) cytology of case of argyrophilic mucinous carcinoma of the male breast is presented. The smear obtained from the tumor showed many loose clusters of atypical cells with abundant granular cytoplasm in the mucous background. Most tumor cells showed a plasmacytoid appearance with eccentric nuclei. Numerous fine granules and a few large droplets were found in the cytoplasm. The characteristic light microscopic feature of this lesion was organoid nest formation of tumor cells in mucous lakes. The Grimelius method revealed numerous argyrophilic granules in the cytoplasm and immunohistochemistry showed a positive reaction for chromogranin A. Thus, this tumor revealed the cytomorphologic characteristics of mucinous as well as argyrophilic carcinoma, simultaneously.

Journal Article↗

PubMed1996

Deficiency of antibody response to hypervariable region of hepatitis C virus in patients with chronic hepatitis C.

BACKGROUND/AIMS: Frequent mutations in the hypervariable region of hepatitis C virus have been suggested to be a cause of persistent infection by providing a way for the virus to escape host immunity. However, the variation rate in the hypervariable region is often low in patients with chronic hepatitis. The aim of this study was to elucidate the mechanism of persistent infection in patients with chronic hepatitis by investigating the relationship between the antibody response to and the variation in hypervariable region. METHODS: The hypervariable regions of 26 clones of six patients with chronic hepatitis C were expressed as proteins fused with glutathione S-transferase, and sera of the patients were serially tested for antibody to these proteins. RESULTS: The extent of antibody response to the hypervariable region differed considerably among the patients. Three patients showed no or only scanty antibody response. These had a lower variation rate in the hypervariable region (0-1.3/year) than in the others with frequent or persistent antibody response (2.1-14.6/year). In two patients, serum samples were found to be reactive with the clones even before the appearance of the clones. In three patients, coexistence of the antibodies and corresponding clones were noted. An augmentation of antibody response always followed rises in serum alanine aminotransferase levels. CONCLUSION: Deficiency of antibody response to the hypervariable region may be one of the causes of persistency in hepatitis C virus infection.

Adult↗

PubMed1996

Methyl jasmonate-induced overproduction of paclitaxel and baccatin III in Taxus cell suspension cultures.

Taxus cell culture may be an alternative source of paclitaxel and related taxane production. Significantly increased amounts of paclitaxel and baccatin III were observed in cultured cells of Taxus species after exposure to methyl jasmonate. Among the three species of Taxus tested, Taxus media showed the highest paclitaxel content while Taxus baccata showed the highest baccatin III content when 100 microM of methyl jasmonate was added to the culture media. Furthermore, the activities of methyl jasmonate and related substances for inducing paclitaxel production were compared in cell suspension cultures of T. media. Methyl jasmonate and its free acid showed the strongest promoting activity. Reduction of the keto group at the C-3 position greatly reduced this activity. cis-Jasmone, which does not have a carboxyl group at the C-1 position, had almost no activity. These results suggest that these two regions of methyl jasmonate are important for promoting the production of paclitaxel and related taxanes in Taxus cell cultures.

Acetates↗

PubMed1996

Permeation from the synovial fluid as nutritional pathway for the anterior cruciate ligament in rabbits.

The anterior cruciate ligament of the knee receives its nutrition from a direct vascular supply and by permeation of nutrients from synovial fluid. In order to quantitate the relative importance of these two routes and to compare the anterior cruciate ligament with the medial collateral ligament, we injected [3H]methyl-glucose as a tracer intravenously or directly into the knee in rabbits. Tracer concentrations in plasma, synovial fluid, the anterior cruciate ligament and the medial collateral ligament were analysed by a pharmacokinetic compartment model developed for this study. The contribution of [3H]methyl-glucose permeation from the synovial fluid was calculated at 59.7% in the anterior cruciate ligament and at 18.1% in the medial collateral ligament. We concluded from these results that the nutrition for the medial collateral ligament, which is an extraarticular structure, is provided mainly by its vascular supply. In contrast, synovial fluid permeation is an important transport route for small molecules for the normal anterior cruciate ligament.

Animals↗

PubMed1996

Effect of protein restriction on the messenger RNA contents of bone-matrix proteins, insulin-like growth factors and insulin-like growth factor binding proteins in femur of ovariectomized rats.

It has been reported that loss of ovarian oestrogen after menopause or by ovariectomy causes osteoporosis. In order to elucidate the effect of dietary protein restriction on bone metabolism after ovariectomy, we fed ovariectomized young female rats on a casein-based diet (50 g/kg diet (protein restriction) or 200 g/kg diet (control)) for 3 weeks and measured mRNA contents of bone-matrix proteins such as osteocalcin, osteopontin and alpha 1 type I collagen, insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) in femur. Ovariectomy decreased the weight of fat-free dry bone and increased urinary excretion of pyridinium cross-links significantly, although dietary protein restriction did not affect them. Neither ovariectomy nor protein restriction affected the content of mRNA of osteopontin and osteocalcin; however, ovariectomy increased and protein restriction extensively decreased the alpha 1 type I collagen mRNA content in bone tissues. Ovariectomy increased IGF-I mRNA only in the rats fed on the control diet. Conversely, protein restriction increased and ovariectomy decreased the IGF-II mRNA content in femur. Furthermore, the contents of IGFBP-2, IGFBP-4 and IGFBP-5 mRNA increased, but the content of IGFBP-3 mRNA decreased in femur of the rats fed on the protein-restricted diet. In particular, ovariectomy decreased the IGFBP-2 mRNA content in the protein-restricted rats and the IGFBP-6 mRNA content in the rats fed on the control diet. These results clearly show that the mRNA for some of the proteins which have been shown to be involved in bone formation are regulated by both quantity of dietary proteins and ovarian hormones.

Animals↗

PubMed1996

Case report: agranulocytosis induced by interferon-alpha therapy for chronic hepatitis C.

A 60-year-old woman presented with chronic active hepatitis C whose HCV-RNA genotype was II according to Okamoto's classification and serum HCV-RNA concentration was 10(4) copies/mL. Agranulocytosis was induced 13 days from the commencement of interferon (IFN)-alpha 2b (6 MU/day) therapy, so the IFN therapy was immediately discontinued. The agranulocytosis improved rapidly with the administration of a granulocyte colony stimulating factor (G-CSF). The possibility that IFN was associated with maturational arrest of myeloid progenitor cells was considered. During the course of 3 years of follow-up, her liver function has remained normal and serum HCV-RNA remains negative.

Agranulocytosis↗

PubMed1996

Analysis of HLA alleles in Japanese patients with cirrhosis due to chronic hepatitis C.

Hepatitis C virus (HCV) leads to chronic liver disease in at least 50-60% of infected people and approximately 40-50% of these patients will go on to develop cirrhosis due to chronic hepatitis C (HCV-C). The pathogenic mechanisms that result in HCV-C are unknown. Sixty Japanese patients with HCV-C were examined for HLA-A, B, C and DR alleles by serologic typing and for HLA-DQB1 alleles by DNA typing using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. As the control population, 293 healthy un-related Japanese were used. The frequencies of HLA-B61, C(omega)3, DR4, DQB1*0401 and DQB1*0402 were increased, while those of HLA-DR9, DQB1*0301 and DQB1*0303 were decreased in the patients. The co-ordinate increase in the frequency of HLA-DR4, DQB1*0401 or 0402 and decrease in the frequency of DR9 or DQB1*0303 were suggestive of a strong linkage disequilibrium between HLA-DR4 and DQB1*0401 or 0402 and between HLA-DR9 and DQB1*0303, respectively. From the odds ratio (OR) analysis, the combinations of HLA-C(omega)3+ DR4-DQB1*0401 or 0402, or HLA-B61 + DR4 - DQB1*0401 or 0402 increased the risk for developing HCV-C when compared to each HLA allele alone. This suggested an additive effect for these classes I and II HLA allele combinations in HCV-C. In contrast, HLA-DR9-DQB1*0303 and DQB1*0301 may confer resistance to this disease. These results suggest the existence of HLA-linked susceptibility genes to HCV-C.

Adult↗

PubMed1996

Extracorporeal shock wave lithotripsy in von Willebrand's disease.

A renal calculus in a patient with von Willebrand's disease was successfully fragmented by extracorporeal shock wave lithotripsy (ESWL) with the administration of Haemate P. No serious bleeding was observed after ESWL. With supplementation of the missing von Willebrand's factor, ESWL may be applied to patients with this bleeding diathesis.

Adult↗

PubMed1996

Renal response to L-arginine in salt-sensitive patients with essential hypertension.

This study examined whether disturbances in nitric oxide formation contribute to renal dysfunction in salt-sensitive essential hypertensive patients. We evaluated the effects of intravenous administration of L-arginine (500 mg/kg given over 30 minutes) on systemic and renal hemodynamics in 23 patients with mild essential hypertension during 1 week of a low NaCl diet (50 mmol/d) followed by 1 week of a high NaCl diet (340 mmol/d). Patients were classified as salt sensitive (n=10) or salt resistant (n=13) based on salt-induced changes in their blood pressures. Salt loading increased renal vascular resistance but not renal plasma flow in salt-sensitive patients. The L-arginine-induced renovascular relaxation was significantly reduced by a high NaCl diet (renal vascular resistance: low NaCl -12.4 +/- 2.3% versus high NaCl -7.1 +/- 1.8%, P < .001) in salt-sensitive patients, whereas it was unchanged in salt-resistant patients. The increase in plasma cGMP in response to L-arginine was also reduced by a high NaCl diet in the salt-sensitive patients (low NaCl 49 +/- 7% versus high NaCl 36 +/- 8%, P < .05) but not in the salt-resistant patients (low NaCl 51 +/- 6% versus high NaCl 58 +/- 6%). These findings suggest that NaCl loading in salt-sensitive patients with mild essential hypertension reduces the ability of L-arginine to produce nitric oxide in the endothelium of the renal vasculature.

Arginine↗

PubMed1996

A preliminary study on inherited tooth morphology characters of Japanese and Chinese young adults--with special reference to the Carabelli tubercle.

A comparative study on inherited tooth morphology characters, in particular the incidence of Carabelli tubercles in the maxillary dentition, was conducted on standardized stone casts obtained from 240 Japanese (124 males (male) and 116 females (females)) and 160 Chinese (74 male, 86 female) young adults. The following results were obtained: 1) No significant differences in the incidence of Carabelli tubercles according to sex or body height were found between the two groups. 2) However, significant differences in the incidence of Carabelli tubercles according to sex were found in both groups. The tubercles occurred more frequently in males. 3) Significant differences between the bilateral and unilateral occurrence of Carabelli tubercles were observed in both the Japanese (p < 0.05) and Chinese (p < 0.01) groups; Carabelli tubercles on upper first molars were always bilateral. 4) The highest incidence of Carabelli tubercles was found in individuals with a body height of 166 approximately 175 cm in both groups, and a significant difference (p < 0.05) between the 156 approximately 165 cm and 166 approximately 175 cm groups was particularly evident in the Japanese adults. The authors postulate that bilateral occurrence of Carabelli tubercles was originally an inherited character in the molar region, but that the character was inhibited during the process of evolution of the masticatory system and regression of the molar dentition.

Adult↗

PubMed1996

[Results of genitoplasty for virilized genitalia of 41 females with congenital adrenal hyperplasia].

OBJECTIVE: The results of genitoplasty performed at our clinic for 41 female patients with congenital adrenal hyperplasia (CAH) were reviewed. PATIENTS: Among 57 females with CAH (56 with 21-hydroxylase deficiency and 1 with 11 beta-hydroxylase deficiency) diagnosed between 1961 and 1995, 41 underwent genitoplasty. For the rest of 16 patients, 1 received already clitorectomy, 11 (19%) needed no surgical reconstruction, 2 died before surgery, and 2 are in a waiting list for surgery. RESULTS: According to Prader's classification of virilized genitalia, 41 patients who received surgery included 8 of type I, 10 of type II, 17 of type III, and 4 of type IV. There was no patients of type V, and 2 were not classified because of previous surgery. Four patients underwent genitoplasty 7 times in total before visiting us. The age receiving initial genitoplasty at our clinic ranged from one year and 9 months to 20 years (median: 4 years and 5 months). Follow-up period averaged 17 years with the range of 2 months to 33 years. For enlarged clitoris, clitorectomy (amputation of clitoris) was carried out for 22 patients before 1975 and corporal resection for 17 after 1975. Two patients manifested recurrence of clitoromegaly after the surgery because of either incomplete resection of the clitoris or patient's ignorance of taking glucocorticoid regularly. Thirty-six patients needed labiovaginoplasty. Simple midline cutback was performed for 6 patients and Y-V plasty (skin flap labiointroitoplasty) for 30. Vaginal orifice was not identified in 5 patients at the initial surgery. Two patients received successful second introitoplasty at the older age than 10. Post-operative stenosis of vaginal orifice was confirmed in 6 patients and 3 underwent second introitoplasty. Among 23 patients older than 25 years at present, 7 got married and 4 raised 6 children with assistance of Caesarian section. CONCLUSIONS: Most of female patients with CAH needed genital plastic surgery including clitoroplasty and labiovaginoplasty. Corporal resection for enlarged clitoris with sufficient hormone therapy brought a satisfactory result. Y-V plasty for labiovaginoplasty proved to be an excellent method, especially from cosmetic viewpoint, but remained some problems as one stage operation including difficult identification of vaginal orifice and post-operative stenosis of introitus in some patients.

Adrenal Hyperplasia, Congenital↗

PubMed1996

[Application of laser spectroscopy for 13C-breath tests].

A new device Tunable Diode Laser Spectroscopy (LS) was developed for the analysis of isotope ratios of 13CO2/12CO2. Its applicability for breath tests was validated. The exhaled breath is collected in a 2 l aluminum bag, of which CO2 is separated by cryogenic system and introduced into LS. Repeat measurements (8 times) of two kinds of gases (delta 13C:-2.62 and - 1.14%) revealed 0.045% and 0.065% variation (IS.D.), from which precision of measurement was estimated as 0.2% (3S.D.). Seven healthy volunteers were given orally different dose of 13C-glycine (50 mg-200 mg in 5 subjects) and 13C-methacetin (30 mg and 150 mg in 2 subjects). One patient with gastric ulcer with helicobacter pylori (HP) infection was given 100 mg of 13C-urea. Serial breath samples (9-15) were taken and measured both by LS and mass spectrometer (MS) thereafter. Appreciable peaks were obtained at 30-50 min. after glycine and methacetin ingestions. The height of the peaks were dose dependent. Increased excretion of 13CO2 characteristics to HP infection was obtained in 13C-urea breath test. Measured values with LS were identical with those measured with MS (60 samples) with the range of difference within 0.2% (3S.D.). [Y (LS) = 1.02X (MS) + 0.55, r = 0.996] We conclude the LS is suitable for various 13C-breath tests.

Adult↗

PubMed1996

[Prognostic factors of renal cell carcinoma: a multivariate analysis].

In a series of 104 patients with renal cell carcinoma, a variety of clinical and histological factors were analyzed to establish their value as prognostic factors. In a univariate analysis (log-rank test), the presence or absence of symptoms, tumor size, pT, N, M, pV categories, TNM stage, Robson stage, nuclear grade and cell type were significantly associated with cause-specific survival, while age, sex and tumor side were not. In a multivariate analysis using Cox's proportional hazard model of 73 informative cases, only N (0 vs. 1-3) and M (0 vs. 1) categories of stage and nuclear grade (1-2 vs. 3) proved to be independent prognostic markers.

Aged↗