Search PubMed⌕ Search

Biomedical subjects

S Higashi

Publications and source records attributed to S Higashi.

At least 55 records · Page 3Linked to original sources
PubMed1999

Antacids have no influence on the pharmacokinetics of rabeprazole, a new proton pump inhibitor, in healthy volunteers.

AIM: This randomized, open-label, crossover study was conducted to evaluate the effect of a single dose of antacid, aluminum and magnesium hydroxide suspension, on pharmacokinetics of rabeprazole in healthy male volunteers. SUBJECTS AND METHODS: Twelve subjects were randomly divided into 6 groups of 2 subjects each, and received 20 mg of rabeprazole either without antacid, concomitantly with antacid, or one hour after administration of antacid in three experimental arms with washout period of one week. The concentrations of rabeprazole in plasma were determined by high performance liquid chromatography. RESULTS: Rabeprazole was well tolerated at the 20 mg dose level when given with or without antacid. The pharmacokinetic parameters, Cmax, t(max), AUC and t1/2, showed no statistically significant differences when rabeprazole was administered alone, concomitantly with antacid or one hour after antacid administration. CONCLUSION: No influence of single dose of antacid on pharmacokinetics of rabeprazole was observed.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

Expression of cholesterol 7alpha-hydroxylase and delta(4)-3-ketosteroid 5beta-reductase genes in rat pancreatic hepatocyte-like cells.

Hepatocyte-like cells have been observed in the pancreas of the rat. We examined the bile acid biosynthetic function of these cells to determine whether they were real hepatocytes. This study investigated the existence of two liver-specific enzymes involved in bile acid biosynthesis (cholesterol 7alpha-hydroxylase and delta(4)-3-ketosteroid 5beta-reductase) in the hepatocyte-like cells. We could demonstrate cholesterol 7alpha-hydroxylase activity and its circadian rhythm in the hepatocyte-like cells. Northern blot analysis demonstrated the expression of messenger RNA for the 7alpha-hydroxylase and delta(4)-3-ketosteroid 5beta-reductase in the pancreatic hepatocyte-like cells. To measure the amount of the messenger RNA, we used the competitive polymerase chain reaction method for the 7alpha-hydroxylase. This quantitation revealed the existence of a circadian rhythm of cholesterol 7alpha-hydroxylase messenger RNA in the hepatocyte-like cells. These results indicated that bile acid biosynthesis was performed in the pancreatic hepatocyte-like cells as noted as in the liver parenchymal cells.

Animals↗
PubMed1999

[Arterial infusion therapy with implantable port for inoperable hepatobiliary tumors].

PURPOSE: To assess the clinical utility of arterial infusion therapy with implantable port for inoperable malignant hepatobiliary tumors. MATERIALS AND METHODS: Twenty-seven patients with advanced hepatobiliary tumors (M:F = 14:13, mean age 63.6, 11 cases with metastases from colon cancer, 4 cases from gastric cancer, 5 cases with gallbladder cancer, 3 cases with cholangiocarcinoma, 2 cases with cholangiocellularcarcinoma, 1 case with hepatocellular carcinoma and 1 with pancreatic cancer) were treated with arterial infusion ports which were placed via left subclavian artery or femoral artery. The regimens used were FEM for 5 cases, EEP for 2 cases and FP for 20 cases. RESULTS: Overall mean survival date was 241.8 days. The numbers of cases with CR, PR, NC and PD were 1, 6, 10 and 10, respectively, and the effective rate was 25.9%. Mean survivals of cases with cholangiocellularcarcinoma, metastases from gastric cancer and colon cancer were 715 days, 324.3 days and 245.9 days, respectively. Severe gastrointestinal side effects (> grade 3) were not observed. Serious bone marrow suppressions were frequently observed with FEM and EEP, but were rare with FP (10%). DISCUSSION: Arterial infusion therapy with implantable port is clinically useful for advanced cholangiocancer and metastases from the gastrointestinal system. This system contributes to the quality of life of patients, since the infusion procedure is simple and can be archived in the outpatient clinics.

Adult↗
PubMed1998

Quantitative trait loci affecting 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in the rat.

The incidence of tongue carcinomas (TCs) induced by oral administration of 4-nitroquinoline 1-oxide in rats is strain dependent. The inbred Dark-Agouti (DA) strain showed a much higher susceptibility to large mass-forming infiltrative TCs than did the Wistar-Furth (WF) strain. Our previous study (M. Kitano et al, Jpn. J. Cancer Res., 87: 1097-1101, 1996) on crosses between these two strains postulated a dominant susceptibility gene in DA and a dominant resistance gene in WF rats. The present study mapped these loci by analyzing the backcrosses to each parent with simple sequence repeat polymorphisms. Five quantitative parameters were analyzed: (a) the number of TCs > 5 mm in diameter; (b) the total number of TCs per rat; (c) the diameter of the largest TCs (DTCmax values); (d) the number of non-TC cancers per rat; and (e) and the number of cancers of any site per rat. All of these parameters were closely correlated (P < 0.0001). DA rats had a semidominant gene (Stc1) favoring the development of 4-nitroquinoline 1-oxide-induced cancers on chromosome 19, closely linked to D19Mit9. Peak linkage was observed 4 cM distal from D19Mit9, with a logarithm of the odds (lod) score of 5.72 for the number of large TCs and 6.08 for the DTCmax. On the other hand, WF rats had a semidominant gene (Rtc1) mapped between D1Mit1 and D1Mit3, approximately 20 cM from D1Mit1, with a peak lod score of 3.30 for both the number of large TCs and the DTCmax. The main effect of Rtc1 seemed to be to reduce the size of the TCs. The action of these genes was dose dependent and cooperative. The final incidence of TC in DA, WF, F1, and backcross rats seemed to be explained by combinations of genotype at these two loci. Possible candidate genes for Stc1 and Rtc1 are discussed.

4-Nitroquinoline-1-oxide↗
PubMed1998

Assay of 25-hydroxyvitamin D3 1 alpha-hydroxylase in rat kidney mitochondria.

An assay method for 25-hydroxyvitamin D3 1alpha-hydroxylase [calcidiol, NADPH: oxygen oxidoreductase (1-hydroxylating), EC 1.14. 13.13] in rat kidney is described. The mitochondrial and nuclear fraction was solubilized effectively with 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate(Chaps). By subsequent ultracentrifugation of the solubilized suspension the effect of inhibitory factor(s) in mammals was removed. The enzyme was then assayed by the reconstitution method using saturated amounts of adrenodoxin and NADPH-adrenodoxin reductase. Products were analyzed by HPLC, monitoring absorbance at 265 nm. The enzyme activity depended on not only pH of the medium but also the kind of buffers. N,N-Bis(2-hydroxyethyl)glycine was the best buffer. At 30 degrees C, the reaction velocity was linear at least up to 10 min, by which time enough amounts of the product needed for analysis were formed. The enzyme activity was linear to a protein concentration up to 0.8 mg of protein/ml. Under the best assay conditions established, the maximal velocity of enzyme in the rachitic rat was 12.9 pmol of product/min/mg of protein, which was 30- to 1000-fold higher than those reported by other authors with the enzyme of rachitic rat. Michaelis constant was 1.8 microM. Specific activity with the enzyme of normal rat was 0.25 pmol of product/min/mg.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1998

Transport mechanisms of a glycoside, p-nitrophenyl-beta-D-glucopyranoside, across rat small intestinal brush-border membranes.

We examined the mechanism of p-nitrophenyl-beta-d-glucopyranoside (p-NP-beta-d-Glc) transport in brush-border membrane vesicles from rat small intestine. The initial uptake rate showed an overshoot phenomenon in the presence of an inwardly directed sodium-ion concentration gradient. The overshoot disappeared when the sodium-ion concentration gradient was replaced with a potassium ion concentration gradient. d-Glucose and p-NP-beta-D-Glc analogues inhibited the uptake, whereas uridine, leucine and disaccharide did not. Data on the concentration dependence of p-NP-beta-D-Glc uptake indicated that two carrier-mediated systems are involved. The uptake via the high-affinity site required an inwardly directed sodium-ion concentration gradient, while the uptake via the low-affinity site proceeded such a gradient. D-Glucose competitively inhibited the initial uptake of p-NP-beta-D-Glc via the high-affinity site with a Ki value of 301 microM. The p-NP-beta-D-Glc is transported in the small intestine via both the same carrier-mediated transport system that takes up D-glucose and a distinct low-affinity carrier-mediated transport system.

Alkaline Phosphatase↗
PubMed1998

Myocardial fatty acid metabolism in diabetic mice with 125I-BMIPP.

In patients with diabetes mellitus, the existence of diabetic cardiomyopathy was substantiated. This study was undertaken to evaluate the myocardiac fatty acid metabolism of diabetic mice (n = 21) and controls (n = 21) in 125I-BMIPP in fasted and unfasted states. 125I-BMIPP of 370 kBq was given and thirty minutes later, animals from both groups were killed. Samples of hearts, liver and other organs were removed, weighed and then counted in a scintillation counter. The percent injected dose/g of hearts of diabetic mice was significantly reduced compared to controls in unfasted (p < 0.05) and fasted (p < 0.01) groups. These findings may reflect impaired fatty acid utilization of the hearts in diabetic mice compared to controls.

Animals↗
PubMed1998

[Right ventricular myxoma in a 71-year-old female].

Right ventricular myxoma in elderly is very rare and this is the 36th case report of right ventricular myxoma in Japan. A healthy 71-year-old female with no symptoms or constitutional signs except heart murmur was hospitalized. Findings of transthoracic echocardiogram, CT scan, MRI and angiocardiogram demonstrated a mobile tumor in the right ventricular outflow tract. Transesophageal echocardiogram clearly revealed that the stalk was arising from the right ventricular free wall. Under cardiac arrest, right atriotomy was made and a gelatinous tumor (4.5 x 2 x 2 cm in size, 7.3 g in weight) was excised with 5 mm of surrounding endocardium and a few millimeters of underlying myocardium through the tricuspid valve. Histopathologically, the tumor was diagnosed as a myxoma. Her postoperative course was uneventful.

Aged↗
PubMed1998

Alteration of low-temperature susceptibility of the cyanobacterium Synechococcus sp. PCC 7002 by genetic manipulation of membrane lipid unsaturation.

Cyanobacteria acclimate to low temperature by desaturating their membrane lipids. Mutant strains of Synechococcus sp. PCC 7002 containing insertionally inactivated desA (Delta12 acyl-lipid desaturase) and desB (omega3 acyl-lipid desaturase) genes were produced, and their low-temperature susceptibility was characterized. The desA mutant synthesized no linoleic acid or alpha-linolenic acid, and the desB mutant did not produce alpha-linolenic acid. The desA mutant grew more slowly than the wild-type at 22 degrees C and could not grow at 15 degrees C. The desB mutant could not continuously grow at 15 degrees C, although no observable phenotype appeared at higher temperatures. It has been shown that expression of the desA gene occurs at 38 degrees C and is up-regulated at 22 degrees C, and that the desB gene is only expressed at 22 degrees C. These results indicate that the expression of the desA and desB genes occurs at higher temperatures than those at which a significant decline in physiological activities is caused by the absence of their products. The temperature dependency of photosynthesis was not affected by these mutations. Since chlorosis and inability to grow at 15 degrees C with nitrate was suppressed by the substitution of urea as a nitrogen source, it is very likely that the chilling susceptibility of the desaturase mutants is attributable to nutrient limitation.

Adaptation, Physiological↗
PubMed1998

Diagnosis of the first Japanese patient with 3-oxo-delta4-steroid 5beta-reductase deficiency by use of immunoblot analysis.

UNLABELLED: A 3-oxo-delta4-steroid 5beta-reductase (5beta-reductase) deficiency is difficult to diagnose because severe liver damage can result in a similar pattern of metabolite excretion. We investigated the usefulness of immunoblot analysis for diagnosis of 5beta-reductase deficiency and quantitatively analysed urinary bile acids by gas chromatography-mass spectrometry in a 5-month-old Japanese boy with severe neonatal cholestasis associated with hypertyrosinaemia. A liver sample was examined by immunoblot analysis using monoclonal antibodies against 5beta-reductase. Urinary 3-oxo-delta4 bile acids accounted for 88.3% of total bile acids, 5alpha-bile acids for 0.9%, and primary bile acids for 9.1%. Immunoblot analysis of the liver tissue showed an indistinct band of 5beta-reductase. CONCLUSIONS: These findings suggest that this patient had a secondary 5beta-reductase deficiency due to severe liver damage, even though 3-oxo-delta4 bile acids constituted more than 70% of total urinary bile acids. However, the patient may possibly have had an inherited 5beta-reductase deficiency.

Amino Acid Metabolism, Inborn Errors↗
PubMed1998

Host genes affecting survival period of chemically induced bladder cancer in mice.

Treatment of C57BL/6 J (B6) and NON male mice with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) resulted in a high incidence of bladder cancer. The mean survival period, however, differed significantly by strain: 481+/-219 days in B6 (n = 31) and 203+/-119 days in NON (n = 30) (P < 0.0001). Major causes of death were renal failure due to obstruction of the urinary tract, or local invasion of tumors. The fact that the BBN-treated NON x B6 reciprocal F1 mice had survival periods as short as those of the parental NON mice suggests a genetically dominant susceptibility in NON or recessive resistance in B6. A linkage analysis of 248 back-cross mice to B6 suggested at least two quantitative trait loci determining the length of the survival period: one was mapped close to D2Mit260 (logarithm of odds, LOD, score 2.21), a microsatellite marker locus 83 cM from the centromere on chromosome 2, and another was close to D6Mit159, 7 cM from the centromere on chromosome 6 (LOD score 2.51).

Animals↗
PubMed1998

Do cerebral aneurysms originate at the site of medial defects? Microscopic examinations of experimental aneurysms at the fenestration of the anterior cerebral artery in rats.

BACKGROUND: The role of medial defects on cerebral aneurysm formation remains obscure. To examine whether cerebral aneurysms originate at the site of medial defects, we determined the exact locations of both the origin of experimental aneurysms and medial defects at the apex of fenestrations of the anterior cerebral artery (ACA) in rats. METHODS: Cerebral aneurysms were induced in rats by means of the combination of ligation of the unilateral common carotid artery and induced hypertension. The ACA opposite the ligation was examined under a light microscope. RESULTS: Medial defects, which could be observed in approximately one-half of the fenestrations, existed always around the lateral margin of the intimal pads. On the contrary, early aneurysmal lesions exclusively occurred at the portion just medial to the intimal pads. Subsequently, both pads and defects seemed to be involved in aneurysm walls. CONCLUSION: These results clearly indicate that cerebral aneurysms do not originate at the site of medial defects.

Animals↗
PubMed1998

Molecular interaction between factor VII and tissue factor.

Complex formation between serine protease factor VIIa (VIIa) and tissue factor (TF) dramatically enhances the catalytic activity of VIIa, leading to the initiation of extrinsic blood coagulation. The recently determined crystal structure of the complex formed between VIIa and the extracellular domain of TF has revealed in detail the interacting surfaces of the two molecules. Mutational and biochemical studies have further identified regions of VIIa and/or those of TF essential for the high affinity interaction. These studies indicate that the regions extending from the gamma-carboxyglutamic acid domain through the first epidermal growth factor-like domain and protease domain of VIIa are involved separately in the interaction with the distinct sites of TF. The interaction of TF with the protease domain of VIIa apparently induces a conformational transition of the VIIa active site. Studies of the chemical modification of VIIa provided a model for the mechanism of TF-mediated acceleration of VIIa activity. In this model, the protease domain of VIIa exists in equilibrium between minor active and dominant zymogen-like inactive conformational states, and preferential binding of TF to the active state leads to a shift in equilibrium into the active state, thereby accelerating VIIa activity. Overall docking of TF with VIIa in the presence of phospholipids further supports a recognition of macromolecular substrates, such as factors IX and X. Therefore, single VIIa-TF interaction contains several distinct mechanisms for enhancing the coagulant activity of VIIa, which may be important for the initiation of coagulation specifically mediated by TF. Studies of the interaction between VIIa and TF provide not only a detailed understanding of the regulated initiation of blood coagulation but also the potential to design novel anticoagulants for the treatment of thrombotic diseases.

Amino Acid Sequence↗
PubMed1998

Role of tissue inhibitor of metalloproteinases-2 (TIMP-2) in regulation of pro-gelatinase A activation catalyzed by membrane-type matrix metalloproteinase-1 (MT1-MMP) in human cancer cells.

To clarify the regulatory mechanism of pro-gelatinase A (proGelA) activation at a cellular level, expression of gelatinase A (GelA), three MT-MMPs, and TIMP-2 was examined with 11 human cancer cell lines cultured in the presence and absence of stimulants. MT1-MMP mRNA was expressed in 8 cell lines, while MT2-MMP and MT3-MMP mRNAs were expressed in fewer cell lines. The cells with high proGelA activation strongly expressed MT1-MMP mRNA but not MT2-MMP and MT3-MMP mRNAs, suggesting that MT1-MMP was responsible for the proGelA activation in the cancer cells. Treatments with concanavalin A (Con A) and a phorbor ester (TPA) enhanced the MT1-MMP expression, but only Con A stimulated the proGelA activation in many cell lines. In HT1080 fibrosarcoma cells, however, TPA also stimulated the activation. The level of TIMP-2 secreted into culture medium inversely correlated with proGelA activation. For example, 2 squamous cell carcinoma lines (HSC-3 and HSC-4) and 3 HT1080 clones, which efficiently activated proGelA, secreted little TIMP-2 into medium, whereas other cell lines and other HT1080 clones, which hardly activated proGelA, secreted TIMP-2 at high levels. When HSC-3 cells were incubated with TIMP-2 protein or transfected with TIMP-2 cDNA, the proGelA activation was strongly inhibited. These results indicated that extracellular TIMP-2 was an important negative regulator of proGelA activation. However, the level of extracellular TIMP-2 was not consistent with that of TIMP-2 mRNA in some cell lines. Other experimental results suggested that TIMP-2 might be rapidly metabolized after binding to MT1-MMP, and Con A treatment might stabilize the complex of TIMP-2 and MT1-MMP on cell membranes.

Catalysis↗
PubMed1998

Gigantic pyoderma gangrenosum.

A 71-year-old Japanese female with gigantic pyoderma gangrenosum is reported. The pyoderma lesions had been treated as an infectious condition for seventeen months and had extended to enormously large areas. The nature of the chronic type of pyoderma gangrenosum may need to be stressed, even for dermatologists.

Aged↗
PubMed1998

Reversibility of retinal flow abnormalities is disease-duration dependent in diabetic rats.

Decreased retinal blood flow has been measured in streptozotocin (STZ)-induced diabetes of 1 week's duration, and primary insulin intervention was effective in maintaining normal retinal blood flow in diabetic rats. Retinal blood-flow abnormalities precede clinical diabetic retinopathy in both diabetic animals and patients. An important characteristic of diabetic retinopathy is the difficulty of reversibility once it has been established. Because altered retinal hemodynamics is a possible marker of early diabetic retinopathy, we investigated in this study whether retinal blood-flow changes in rats can be normalized by secondary insulin intervention following short and chronic periods of untreated STZ-induced diabetes. Subcutaneous insulin pumps were placed into diabetic rats for 1 week after 1 week of diabetes (2-week group) and after 3 weeks of diabetes (4-week group). Retinal circulatory parameters were determined using image analysis of video fluorescein angiogram recordings. For the 2-week group, retinal blood flow was significantly (P < 0.05) reduced in the untreated diabetic rats compared with nondiabetic and insulin-treated diabetic rats (80.6+/-29.2, 131.9+/-50.1, and 151.3+/-54.0 pixels2/s respectively). Retinal blood flow was also significantly (P < 0.05) reduced in the 4-week untreated diabetic rats compared with nondiabetic rats (95.7+/-22.2 vs. 125.7+/-29.5 pixels2/s). In contrast to the shorter-duration group, insulin treatment for 1 week after 3 weeks of diabetes did not totally normalize retinal blood flow (117.5+/-32.4 pixels2/s). These results suggest that vascular abnormalities could become more resistant to normalization following short-term (1 week) insulin treatment after longer periods of untreated diabetes.

Animals↗