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Biomedical subjects

H Sakurai

Publications and source records attributed to H Sakurai.

At least 217 records · Page 12Linked to original sources
PubMed1998

TGF-beta-activated kinase 1 stimulates NF-kappa B activation by an NF-kappa B-inducing kinase-independent mechanism.

Several mitogen-activated protein kinase kinase kinases (MAPKKKs), including NF-kappa B-inducing kinase (NIK), play critical roles in NF-kappa B activation. We isolated cDNA for human TGF-beta activated kinase 1 (TAK1), a member of the MAPKKK family, and evaluated its ability to stimulate NF-kappa B activation. Overexpression of TAK1 together with its activator protein, TAK1 binding protein 1 (TAB1), induced the nuclear translocation of NF-kappa B p50/p65 heterodimer accompanied by the degradation of I kappa B alpha and I kappa B beta, and the expression of kappa B-dependent reporter gene. A dominant negative mutant of NIK did not inhibit TAK1-induced NF-kappa B activation. These results suggest that TAK1 induces NF-kappa B activation through a novel NIK-independent signaling pathway.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Development of a highly sensitive and specific two-site enzyme immunoassay for parathyroid hormone (1-34): application to pharmacokinetic study on intranasal parathyroid hormone (1-34) in human.

A highly sensitive and specific two-site enzyme immunoassay for parathyroid hormone (1-34) (PTH(1-34)) and its usability for the pharmacokinetic study are described. Plasma samples were incubated simultaneously with 2,4-dinitrophenylated anti-PTH(1-34) IgG and anti-PTH(1-34) Fab'-beta-D-galactosidase conjugate. The immune complex formed of the three components was trapped onto (anti-2,4-dinitrophenyl group) IgG-coated polystyrene balls. beta-D-Galactosidase activity bound to the polystyrene balls was assayed by fluorometry. The practical detection limit of PTH(1-34) was 50 fg (12 amol)/0.05 ml of sample and 1 pg/ml as the concentration and practically no interference occurred by PTH(1-84) and PTH-related protein (1-34) up to 300 pg/ml and 10 ng/ml, respectively. The application of this method has enabled us to directly estimate the bioavailability of PTH(1-34) dosed intranasally at the prescribed level (0.090 mg). The pharmacokinetic parameters of the intranasal PTH(1-34) (n = 4) thus estimated were as follows: the area under the plasma concentration-time curve (AUC) = 20,500+/-15,900(SD) pg.min/ml; the mean residence time (MRT) = 194+/-16.3(SD) min; and the maximal concentration (Cmax) = 98+/-51 (SD) pg/ml with the maximal time (Tmax) = 35.0+/-12.2(SD) min.

Adult↗
PubMed1998

Determination of the bioavailability of intranasal elcatonin in humans: development of a sandwich transfer enzyme immunoassay for elcatonin.

A sandwich transfer enzyme immunoassay for elcatonin (ECT) and its usability for the pharmacokinetic study are described. The anti-salmon calcitonin (SCT) antibody was used for the present assay. The assay procedure consisted of the reaction of ECT with 2,4-dinitrophenylbiotinyl anti-SCT IgG and anti-SCT Fab'-beta-D-galactosidase conjugate, trapping onto (anti-2,4-dinitrophenyl bovine serum albumin) IgG-coated polystyrene balls, eluting with epsilonN-2,4-dinitrophenyl-L-lysine and transferring to streptavidin-coated polystyrene balls and fluorometric detection of beta-D-galactosidase activity. The practical detection limit of ECT was 0.15 pg (44 amol)/50 microl of sample and 3 pg/ml as the concentration. The application of this method has enabled us to directly estimate the bioavailability of ECT dosed intranasaly at a therapeutic level (100 IU, 17 microg) for its anti-osteoporotic effect as compared to an intramuscular dose (40 IU, 6.7 microg). The pharmacokinetic parameters of the intranasal ECT (n = 6) thus estimated were as follows: the area underthe serum concentration-time curve (AUC) = 2,570 +/- 1,650 (SD) pg x min/ml, and the maximal concentration (Cmax) = 60 +/- 25 (SD) pg/ml with the maximal time (Tmax) = 17.5 +/- 6.9 (SD) min, when the AUC for the intramuscular ECT (n = 9) = 9,460 +/- 5,870 (SD) pg x min/ml and the Cmax = 165 +/- 79 (SD) pg/ml with the Tmax = 16.1 +/- 4.2 (SD) min.

Administration, Intranasal↗
PubMed1998

[Two staged Starnes operation for Ebstein's anomaly with pulmonary atresia in early infancy--a report of a successful case].

Severe tricuspid valve regurgitation and decreased pulmonary blood flow in neonatal Ebstein's anomaly with pulmonary atresia, may result in cardiac respiratory failure and hypoxemia. The poor natural course and lack of standard surgical treatment make treatment for neonatal Ebstein's anomaly very difficult. The Blalock-Taussig operation was performed for hypoxemia in Ebstein's anomaly associated with pulmonary atresia and severe tricuspid regurgitation on 36th day after birth. On the 63rd day after birth, tricuspid valve orifice closure and right atrium plication (Starnes procedure) were accomplished under cardiopulmonary bypass. Heart failure became controllable and the patient condition was satisfactory at one year after surgery.

Anastomosis, Surgical↗
PubMed1998

Differential role of catalase and glutathione peroxidase in cultured human fibroblasts under exposure of H2O2 or ultraviolet B light.

The purpose of this study was to elucidate the differential contribution of catalase and glutathione peroxidase (GSH-Px) to H2O2 scavenging in cultured human dermal fibroblasts. Responses of the cells in terms of both enzyme activities were examined by using two sorts of inhibitors, 3-amino-1H-1,2,4-triazole (AT) for catalase and DL-buthionine-[S,R]-sulfoximine (BSO) for GSH-Px, under exposure to H2O2 or ultraviolet (UV) B radiation. AT treatment resulted in a decrease in H2O2 scavenging activity, while BSO treatment did not affect H2O2 scavenging. When fibroblasts were exposed to a low concentration of H2O2 (100 microM). AT treatment resulted in a significant decrease in cell survival, but BSO treatment did not affect survival. At higher concentrations of H2O2 ranging from 500 microM to 1 mM, BSO-treated fibroblasts showed reduced survival. In addition, AT treatment was much more cytotoxic in the presence of UVB than BSO treatment. The intracellular levels of H2O2 in fibroblasts treated with AT or BSO were also determined. BSO-treated cells showed similar H2O2 levels to control cells, but the intracellular H2O2 levels of AT-treated fibroblasts were 1.4-fold higher than found in control cells. These results with human dermal fibroblasts indicate that catalase acts as a primary defence against oxidative stress from exogenous or endogenous H2O2 at low concentrations. In contrast, GSH-Px helps protect the cell from damage during exposure to high concentrations of H2O2.

Amitrole↗
PubMed1998

Binding affinity of Cu(II)-VP-16 (etoposide) complex and its analogues to DNA and hydroxyl radical generation during DNA strand breaks.

Conformational effects and affinities of VP-16 (etoposide) and its derivatives to DNA in the presence of Cu(II) ion were examined by circular dichroic (CD) spectra. The Cu(II)/Cu(I) redox kinetics and the hydroxyl radical (.OH) generation from the Cu(II)-complexes were estimated by the stopped-flow kinetics. Based on the results, DNA-cleaving activity of Cu(II)-complexes of VP-16 has been shown to be related with binding affinity of the complex to DNA, Cu(II)/Cu(I) redox and .OH generation, emphasising the mechanism of generated .OH attack to DNA.

Animals↗
PubMed1998

Antiallergic activities of rabdosiin and its related compounds: chemical and biochemical evaluations.

We examined the effects of caffeic acid-containing compounds such as chlorogenic acid, rosmarinic acid and rabdosiin on anti-allergic activities involving active oxygens scavenging activity as well as inhibitory activities of hyaluronidase and beta-hexosaminidase release. Rabdosiin exhibited the highest hyaluronidase-inhibitory activity and scavenging activities against active oxygens species such as superoxide anion radicals and hydroxyl radicals among the tested compounds. Both rabdosiin and caffeic acid inhibited beta-hexosaminidase release from cultured cells more than 90% at 2 mM. The inhibition by rosmarinic acid and chlorogenic acid were weaker than that of rabdosiin. From these results, rabdosiin has been proposed to possess anti-allergic activity.

Animals↗
PubMed1998

In vitro branching tubulogenesis: implications for developmental and cystic disorders, nephron number, renal repair, and nephron engineering.

Branching tubulogenesis of the ureteric bud is critically important for kidney development. Recent findings using three-dimensional cell culture systems for in vitro branching tubulogenesis are likely to shed light on the mechanisms of ureteric bud morphogenesis. Here, we try to unify these findings with those obtained using genetic approaches and organ culture of the embryonic kidney into a working model of ureteric bud branching tubulogenesis. It appears that the balance between branching tubulogenesis facilitating growth factors such as epidermal growth factor receptor ligands, hepatocyte growth factor, insulin-like growth factors, and inhibitory growth factors such as transforming growth factor beta family members may regulate branching morphogenesis. Growth factors induce epithelial cell proliferation, migration, and modulate the expression of a variety of proteins. Downstream in the growth factor-mediated tubulogenesis pathway, extracellular proteases, protease inhibitors, extracellular matrix proteins, and integrins are likely to act as effectors and regulators of branching tubulogenesis. Discussed in some detail are the relevance of insights gleaned from in vitro models of branching tubulogenesis to congenital urogenital abnormalities, cystic kidney diseases, oligonephropathies and hypertension, tubular cell regeneration after injury, and tubular engineering.

Animals↗
PubMed1998

Cytotoxic effect of paclitaxel (taxol) either alone or in combination with irradiation in two rat yolk sac tumour cell lines with different radiosensitivities in vitro.

PURPOSE: To investigate the differences between two rat yolk sac tumour cell lines with different radiosensitivities in paclitaxel sensitivity and in the sensitizing effects of paclitaxel in combination with irradiation. MATERIALS AND METHODS: NMT-1 is a parent radiosensitive cell line and NMT-1R is a variant radioresistant cell line. RESULTS: Clonogenic assay demonstrated almost the same paclitaxel sensitivity with Do of 5.15 nM in NMT-1 and 5.02 nM in NMT-1R. Many apoptotic cells and DNA ladder formations were observed at 24 h after exposure to paclitaxel in both cell lines. The incidence of DNA fragmentation after 24 h exposure to 20 nM paclitaxel was 12.4 +/- 3.3% for NMT-1, and 13.0 +/- 1.9% for NMT-1R. Paclitaxel showed a supra-additive effect in combination with irradiation in both cell lines at 12 h after paclitaxel treatment only when the accumulation of cells in the G2/M phase reached its peak. CONCLUSIONS: Paclitaxel had the same cytotoxic effect in two cell lines with different radiosensitivity due to the induction of apoptosis. A supra-additive effect to radiation was observed with 12 h pretreatment in both cell lines. Paclitaxel may be effective for tumours with a component of different radiosensitivity in combination with irradiation.

Animals↗
PubMed1998

c-Jun N-terminal kinase-mediated AP-1 activation in experimental glomerulonephritis in rats.

We demonstrated activation of transcription factor AP-1 in rat nephrotoxic serum (NTS)-induced glomerulonephritis in a previous report. Here, we evaluate c-Jun N-terminal kinases (JNKs) activity to clarify the molecular mechanisms of AP-1 activation in nephritic glomeruli. Increased JNKs activity was detected in glomeruli isolated from NTS-treated rats. The kinetics of JNKs activation was similar to that of AP-1 activation. Phosphorylated c-Jun at Ser63, one of the target residues for JNK, was also detected in nephritic glomeruli. This is the first report demonstrating JNKs-mediated c-Jun/AP-1 activation in nephritic glomeruli. These results suggest an important role of the JNK-AP-1 signaling pathway in the pathogenesis of glomerulonephritis.

Animals↗
PubMed1998

Placental metastasis from maternal primitive neuroectodermal tumor.

The occurrence of placental metastasis from maternal primitive neuroectodermal tumor (PNET) is extremely rare. A 33-year-old woman at 33 weeks' gestation was admitted to the hospital. She died of the disease on hospital day 28 because the unresectable tumor was located over a wide area of the retroperitoneum. A neonate was delivered by a caesarean section without evidence of disease and has survived to 1 year of age. Pathologically, the tumor consisted of monotonous small round cells with a high nuclear cytoplasmic ratio, including several pseudorosettes and Homer-Wright-type rosettes. On immunohistochemical examination, the tumor cells were positively stained for neuron-specific enolase. Microscopically, the placenta showed intervillous metastasis from the maternal PNET. This case may be the first one of placental metastasis from PNET ever reported in the literature.

Adult↗
PubMed1998

Transrectal ultrasonography in evaluation of chronic rectal complications after radiation therapy for carcinoma of the uterine cervix.

RATIONALE AND OBJECTIVES: The authors studied the ability of transrectal ultrasonography (TRUS) to assess chronic rectal complications after radiation therapy for carcinoma of the uterine cervix. METHODS: One hundred twenty-five TRUSs were performed for 67 consecutive patients with carcinoma of the uterine cervix. Transrectal ultrasonography images of the rectal anterior wall and perirectal connective tissue adjacent to the uterine cervix were recorded with real-time scanner with 7.5 MHz transducer. The severity of TRUS abnormalities was graded on a scale developed by the authors. The relationships of the TRUS grade with the clinical grade of chronic rectal complications and with rectal radiation doses were analyzed retrospectively. RESULTS: Thickening of the perirectal connective tissue associated with obscuration of the submucosal echogenic layer in rectal anterior wall was observed between 6 months to 2 years after radiation therapy in all 19 patients who developed chronic rectal complications. The TRUS grade correlated with the clinical grade of chronic rectal complications, but did not correlate with rectal radiation doses. CONCLUSIONS: Transrectal ultrasonography can monitor the chronic rectal complications after radiation therapy for the patients with carcinoma of the uterine cervix.

Adult↗
PubMed1998

Altered systemic organ blood flow after combined injury with burn and smoke inhalation.

Systemic organ blood flow was longitudinally determined with fluorescent microspheres after severe thermal injury in unanesthetized sheep. After chronic instrumentation, 20 sheep were subjected to combined injury with 40% body surface area third-degree burn and 48 breaths of cotton smoke insufflation. During the next 72 h of the experimental period, all animals were resuscitated with Ringer's lactate following the Parkland formula. To test the effect of systemic administration of ibuprofen, animals were assigned to the control group (n=11) or the ibuprofen group (n=9). In the ibuprofen group, animals received ibuprofen as a 12 mg/kg bolus injection 1 h after injury and 6 mg/kg/h as a continuous infusion for the next 47 h. After this combined injury, animals exhibited a biphasic hemodynamic alteration, with an initial shock period and a later hyperdynamic period, a phenomenon often seen in severely burned patients. Among multiple organs, the splanchnic organs exhibited more dominant and sustained decreases in regional blood flow, whereas heart and kidney blood flow were maintained at more than 90% of baseline level even in the initial hypovolemic phase. In the postresuscitation period, no organ except the heart showed increased regional blood flow, despite a more than 20% increase in cardiac output. Ibuprofen had effects on early recovery from the initial shock period, and it improved intestinal organ blood flow, suggesting a potential benefit of this drug for severe thermal injury.

Animals↗
PubMed1998

Evidence on N-acetyltransferase allele-associated metabolism of hydrazine in Japanese workers.

Hydrazine (N2H4), which has been categorized as a weak carcinogen, is a chemical with the one of the largest production rates in Japan. We have investigated the effects of acetylation phenotypes on the metabolism of hydrazine. Genotypes of N-acetyl transferases, NAT2*, were determined using polymerase chain reaction for 297 male workers. Biological and exposure monitoring were also conducted. The rapid and intermediate acetylators accounted for 45% each, and the slow acetylators accounted for 10%. Biological half-lives were significantly different among the three acetylation phenotypes (analysis of variance, P < 0.05): 3.94+/-1.70 hours for slow acetylators, 2.25+/-0.37 hours for intermediate acetylators, and 1.86+/-0.67 hours for rapid acetylators. Among Japanese, rapid and intermediate acetylators are the major phenotypes, which is in sharp contrast with those among Caucasians. We conclude that biological monitoring should take genetic factors, which may vary dramatically among different populations, into account.

Adult↗
PubMed1998

Enhanced absorption of calcium after oral administration of maltitol in the rat intestine.

The enhancing effects of maltitol (alpha-D-glucopyranosyl-1,4-sorbitol) on absorption of calcium by the rat intestine have been studied by use of [45Ca]CaCl2 in-vivo. After intragastric administration of [45Ca]CaCl2 solution with maltitol, plasma 45Ca concentration remained at the maximum level for more than 80 min, whereas for animals given [45Ca]CaCl2 solution without maltitol, plasma 45Ca concentration declined sharply after the peak. Determination of 45Ca radioactivity remaining in the various segments of the gastrointestinal tract revealed that administration of maltitol elicited slower gastric emptying and slower intestinal transit, resulting in extensive 45Ca distribution along the small intestine throughout the experimental period. The luminal contents of the small intestine were significantly higher in rats given maltitol than in the control group. These results suggest that the enhancing action of maltitol on intestinal calcium absorption could be attributed to reduced gastrointestinal calcium transit and increased luminal fluid content, presumably because of the osmotic activity of maltitol; this would not only accelerate the dissolution of calcium into the increased luminal contents, but also enable a larger area of the small intestine to absorb calcium for a longer period of time.

Administration, Oral↗
PubMed1998

Cross sectional observation of the effects of carbon disulphide on arteriosclerosis in rayon manufacturing workers.

OBJECTIVE: A prospective cohort study was designed to clarify the relations between occupational exposure to carbon disulphide (CS2) and its effects on arteriosclerosis in workers in 11 Japanese rayon manufacturing factories. This report is a cross sectional baseline observation in the first study year. METHODS: Study subjects were 432 male rayon workers (mean (range) age 35.5 (19.1-47.8); duration of exposure 13.4 (0.3-29.0)) and 402 male referent workers (age 35.8 (18.9-49.8)). Exposure to CS2 was assessed by determining the concentration of 2-thiothiazolidine-4-carboxylic acid (TTCA) in urine. Mean (SD) TTCA was 3.42 (2.73) mg/g creatinine (Cr) (n = 422). About a quarter of the urine samples were > 5 mg/g Cr, a biological exposure index recommended by the American Conference of Governmental Industrial Hygienists. Health effects on arteriosclerosis were evaluated by measuring blood pressure, serum lipids, pulse wave velocity of the aorta, stiffness and blood flow of the carotid artery, and blood coagulation and fibrinolysis indices, and by use of brain magnetic resonance imaging, electrocardiogram (at rest and after exercise), ophthalmograph, and Rose's questionnaire. Information on potential confounding factors was collected by self administered questionnaire. RESULTS: Prevalence of microaneurysm of the retinal artery was significantly higher in workers exposed to CS2 (8.1%) than in referent workers (3.4%), and increased with age. Other examinations did not show any differences between the two groups even after allowance for confounding factors. CONCLUSIONS: Significant effects of CS2 on arteriosclerosis were not found in current rayon manufacturing workers, with the exception of induction of microaneurysm of the retinal artery.

Adult↗