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Biomedical subjects

A Hirose

Publications and source records attributed to A Hirose.

At least 19 recordsLinked to original sources

Pediatric susceptibility to 18 industrial chemicals: a comparative analysis of newborn with young animals.

We comprehensively re-analyzed the toxicity data for 18 industrial chemicals from repeated oral exposures in newborn and young rats, which were previously published. Two new toxicity endpoints specific to this comparative analysis were identified, the first, the presumed no observed adverse effect level (pNOAEL) was estimated based on results of both main and dose-finding studies, and the second, the presumed unequivocally toxic level (pUETL) was defined as a clear toxic dose giving similar severity in both newborn and young rats. Based on the analyses of both pNOAEL and pUETL ratios between the different ages, newborn rats demonstrated greater susceptibility (at most 8-fold) to nearly two thirds of these 18 chemicals (mostly phenolic substances), and less or nearly equal sensitivity to the other chemicals. Exceptionally one chemical only showed toxicity in newborn rats. In addition, Benchmark Dose Lower Bound (BMDL) estimates were calculated as an alternative endpoint. Most BMDLs were comparable to their corresponding pNOAELs and the overall correlation coefficient was 0.904. We discussed how our results can be incorporated into chemical risk assessment approaches to protect pediatric health from direct oral exposure to chemicals.

Age Factors↗

Evaluation of developmental toxicity of 1-butanol given to rats in drinking water throughout pregnancy.

The objective of this study was to evaluate the developmental toxicity of 1-butanol in rats. Pregnant rats were given drinking water containing 1-butanol at 0.2%, 1.0% or 5.0% (316, 1454 or 5654 mg/kg/day) on days 0-20 of pregnancy. A significant decrease in maternal body weight gain accompanied by reduced food and water consumption was found at 5.0%. No significant increase in the incidence of pre- and postimplantation embryonic loss was observed in any groups treated with 1-butanol. Fetal weight was significantly lowered at 5.0%. Although a significant increase in the incidence of fetuses with skeletal variations and decreased degree of ossification was found at 5.0%, no increase in the incidence of fetuses with external, skeletal and internal abnormalities was detected in any groups treated with 1-butanol. The data demonstrate that 1-butanol is developmental toxic only at maternal toxic doses. No evidence for teratogenicity of 1-butanol was noted in rats. Based on the significant decreases in maternal body weight gain and fetal weight, it is concluded that the no observed adverse effect levels (NOAELs) of 1-butanol for both dams and fetuses are 1.0% (1454 mg/kg/day) in rats.

1-Butanol↗

Electron thermal diffusivity due to the electron temperature gradient mode.

Charge neutrality breaks down in the short wavelength toroidal electron temperature gradient mode. In contrast to the ion temperature gradient mode, the wave number normalized by the Debye wave number, k/k(De), appears as a natural scale parameter, rather than the finite Larmor radius parameter k( perpendicular )rho(e). The growth rate and consequent mixing length estimate yields an electron thermal diffusivity large enough to be relevant to tokamaks.

Journal Article↗

Prenatal diagnosis of sustained bradycardia with 1 : 1 atrioventricular conduction.

OBJECTIVES: The aims of this study were to elucidate the clinical course of fetal bradycardia with 1 : 1 atrioventricular conduction, and to discuss the optimal management of affected fetuses in the second and third trimesters of pregnancy. METHODS: The hospital records of five fetuses with the diagnosis of bradycardia (100 bpm) with 1 : 1 atrioventricular conduction between 1981 and 2000 in our institution were reviewed. Atrioventricular conduction was evaluated by simultaneous M-mode echocardiographic tracing of the atria and the ventricles. RESULTS: The gestational ages at referral ranged from 19 to 36 (median, 25) weeks, and fetal heart rates ranged from 60 to 80 (median, 80) bpm. Postnatal electrocardiography revealed sinus bradycardia in four (two of which were siblings) of the five cases, and junctional rhythm in the remaining case. Two fetuses with congenital heart defects (CHDs) were delivered by Cesarean section but died postnatally. The three fetuses without CHDs were delivered vaginally and have survived to date for 6, 8 and 15 years. CONCLUSIONS: Fetal bradycardia with 1 : 1 atrioventricular conduction caused by sustained sinus bradycardia or wandering pacemaker is an important type of fetal arrhythmia. Further investigations with a larger number of cases are required to determine the risk factors for predicting the outcome of affected fetuses.

Bradycardia↗

Role of parallel flow in the improved mode on the STOR-M tokamak.

A novel feature of the H-mode induced by compact torus injection on the STOR-M tokamak is observed. There is almost no change in the radial electric field profiles during and after the L-H transition. The usual hypothesis of the E x B shear stabilization mechanism is therefore unlikely to play a role in this transition. A new mechanism of the stabilization of microinstabilities by parallel flow is suggested as the plausible cause for the transition to this improved regime.

Journal Article↗

Dose- and time-response studies of sodium o-phenylphenate urinary bladder carcinogenicity in rats.

Dose- and time-response studies of urinary bladder carcinogenesis due to orally administered sodium o-phenylphenate (OPP-Na) were performed using 5-week-old male Fischer 344 rats given diets containing 0 (control), 2500, 5000, 10,000, 15,000 or 20,000 ppm OPP-Na for 104 weeks and fed basal diets until 112 weeks (experiment 1). In addition, rats received diets containing 20,000 ppm OPP-Na for 0 (control), 12, 24, 52 or 104 weeks and were killed at week 112 (experiment 2). In experiment 1, the transitional cell carcinoma (TCC) was the major tumor type in the urinary bladder, and the dose-response curve was steep with many tumors occurring at the high doses of 15,000 and 20,000 ppm. The virtually safe dose at a risk level of 10(-6) for TCCs and papillomas was estimated to be 144 ppm by the Weibull model, a high value similar to that for sodium saccharin. In experiment 2, a few TCCs developed after 24 weeks of treatment, but the time-response curve was also steep with the majority of lesions occurring after longer exposure periods. Based on the observed steepness in dose- and time-responses, any implied cancer risk of OPP-Na at the low doses of interest to man must be considered to be very small.

Agrochemicals↗

Inhibition of apoptosis by pentachlorophenol in v-myc-transfected rat liver epithelial cells: relation to down-regulation of gap junctional intercellular communication.

Pentachlorophenol (PCP), a promoter of murine hepatocarcinogenesis, inhibits gap junctional intercellular communication (GJIC) in rat liver epithelial cells in vitro. To test the hypothesis that both inhibition of GJIC and apoptosis contribute to tumor promotion, we investigated the effect of PCP on both GJIC and serum deprivation-induced apoptosis in v-myc-transfected rat liver epithelial cells. The results showed that PCP inhibited apoptosis, as measured by the TUNEL assay and DNA ladder formation. Inhibition of apoptosis was associated with a decrease in GJIC. The study demonstrated that PCP has a potential for inhibiting apoptosis and GJIC, supporting the hypothesis.

Animals↗

Virus-associated hemophagocytic syndrome due to rubella virus and varicella-zoster virus dual infection in patient with adult idiopathic thrombocytopenic purpura.

A 26-year-old woman with idiopathic thrombocytopenic purpura (ITP) was admitted to our hospital because of fever and rash. Blood tests revealed thrombocytopenia, liver dysfunction, coagulopathy, and hyperferritinemia. Bone marrow examination revealed many atypical lymphocytes and some histiocytes with hemophagocytosis. On admission she was diagnosed with rubella virus-associated hemophagocytic syndrome (VHAS), but on laboratory examination, she was seropositive for varicella-zoster virus (VZV)-IgM as well as rubella virus-IgM. She was therefore diagnosed with dual infection by rubella virus and VZV. Her simultaneous rubella virus and VZV infection may have been related to the VAHS pathogenesis. She was treated with prednisolone and gamma globulin therapy and recovered completely.

Adult↗

Primary refractoriness to platelet transfusion caused by Nak(a) antibody alone.

BACKGROUND AND OBJECTIVES: Anti-Nak(a), a platelet-specific antibody, occasionally causes platelet-transfusion refractoriness (PTR) together with human leucocyte antigen (HLA) antibodies. Anti-Nak(a) usually appears after frequent platelet transfusions or pregnancy. We report the first case of PTR caused by anti-Nak(a) alone. MATERIALS AND METHODS: A 19-year-old male patient with testicular tumour showed PTR when receiving his first transfusion of platelets. Screening for platelet antigens and platelet antibodies revealed that he had type I CD36 (Nak(a)) deficiency and that anti-Nak(a), but not anti-HLA, was present before he received his first transfusion. RESULTS: The transfusion of Nak(a)-negative, but HLA non-selected, platelets was effective in raising the platelet count. CONCLUSION: Clinically significant Nak(a) antibody was present as naturally occurring antibody in a platelet glycoprotein IV (CD36)-negative non-transfused male patient.

Adult↗

Emergency abdominal surgery in patients aged 80 years and older.

The outcome of emergency abdominal surgery in elderly patients remains unsatisfactory. We studied factors contributing to the outcome of abdominal emergency surgery in elderly patients, particularly in those aged 80 years and older. Subjects were 61 patients aged 80 years and older (group A) and 108 patients aged from 65 to 79 years (group B) who underwent emergency abdominal surgery between 1983 and 1997. Complications were significantly higher in group A than in group B, with respiratory failure the most common postoperative complication. Mortality rate within 30 days after surgery was also higher in group A (9.8%) than in group B (3.3%). Complications and mortality did not differ significantly between those with and without preexisting concomitant disease in group A. Systemic inflammatory response syndrome (SIRS) was seen in 35 patients in group A and 50 in group B. Severe complications occurred in 62.5% of group A with preoperative SIRS. Mortality in those with SIRS was significantly higher than those without. SIRS is thus a feasible predictor of poor outcome in patients aged 80 years and older who have emergency abdominal surgery and in those aged from 65 to 79 years. Patients with SIRS should initially receive minimal treatment whenever possible, rather than be overtreated, until their conditions stabilize.

Abdomen↗

[Mycosis fungoides terminating in acute myelocytic leukemia].

A 57-year-old woman was admitted to our hospital with suspected leukemia in September 1999. In 1990, systemic erythema had occurred, and mycosis fungoides (MF) had been diagnosed by skin biopsy. Interferon-gamma therapy had not been effective, and the erythema had disappeared after treatment with psoralen and ultraviolet A (PUVA) therapy (1.46 J/cm2). The patient had subsequently done well with a course of topical steroids. On admission this time, the WBC count was 1,600/microliter with 6% blasts. The total nucleated cell count in a bone marrow aspirate was 43.1 x 10(4)/microliter, of which 86.2% were peroxidase-positive blasts. Acute myelocytic leukemia (AML) was diagnosed. Chromosomal analysis demonstrated abnormalities of 48, XX, +4, +8, +add(10)(p11), add(11)(q23) in 10 of 20 cells, and 51, idem, +6, +8, +21, +mar in 8 cells with mixed-lineage leukemia gene rearrangement. Therapies (radiation, chemotherapy and PUVA) for MF, and the altered immune response seen in patients with this disease, especially in the more advanced stages, collectively termed cutaneous T-cell lymphoma (CTCL), suggest that such patients may be at increased risk of a second primary malignancy. To our knowledge, AML has been reported in 8 MF patients including the present one. Attention should be given to the possibility of MF terminating in AML.

Female↗

[Bisphenol.alkylphenols].

Bisphenol A and some alkylphenols such as p-nonylphenol and p-tert-octylphenol, have been noticed as endocrine disruptors, showing estrogenic activities. In this article, the knowledge of endocrine disrupting toxicities of these chemicals is reviewed. These chemicals induce uterus proliferation(in both immature and ovariectomized animals), disruption of estrus cycles, etc. in rodent females. They also induce decreased weights of testes and the accessory organs with the histological atrophy in the males. The lowest adverse effect level for these chemicals is approx. 10 mg/kg/day by oral administration except fetal exposure. Because there are some reports on extremely low dose toxicities by fetal exposure, further investigation is necessary to estimate the full-time safety level.

Animals↗

Toluene inhalation induced epididymal sperm dysfunction in rats.

Toluene is a widely abused inhaled solvent. This study was designed to determine whether toluene abuse affects the reproductive functions or general health of males. Seven-week-old male Sprague-Dawley rats were exposed to toluene vapor inhalation (0, 4000, or 6000 ppm; 2 h/day) daily for 5 weeks. Exposure-related suppression of body weight gain and food consumption were observed. Salivation and lacrimation were observed during exposure periods and intensified with repeated exposure. Rats exposed to 6000 ppm toluene had decreased spleen and thymus weights, as well as suppressed lymphocyte counts. In 6000 ppm group, the epididymal sperm counts, sperm motility, sperm quality and in vitro penetrating ability to zona-free hamster eggs were significantly reduced, while no exposure-related changes in the testes weight or spermatogenesis within testes were detected. Tail-less sperm heads were seen within zona-free eggs incubated with sperm from rats exposed to 6000 ppm toluene, but not control rats. No significant changes were observed in serum luteinizing hormone, follicle-stimulating hormone, or testosterone levels following 1 month of exposure to 6000 ppm toluene. These results indicate that high concentrations of toluene may directly target sperm in the epididymis and disrupt sperm maturation.

Animals↗

Reperfusion induces sublethal endothelial injury.

BACKGROUND: Endothelial cells are pivotal in regulating thrombosis and hemostasis. In this study, we sought to characterize endothelial dysfunction and endothelial cell injury in vitro after hypoxia/reoxygenation. MATERIALS AND METHODS: Cultured human umbilical vein endothelial cells (ECs) were exposed to 120 min of hypoxia followed by reoxygenation. The release of thrombomodulin (TM) and the production of prostaglandin I2 (PGI2) were measured. Endothelial cell injury in hypoxia/reoxygenation was measured by two assays, the Fura-2 release assay and the 51chromium (51Cr) release assay. RESULTS: TM release from ECs during normoxic incubation was undetectable, while it was slightly increased during hypoxic incubation. After reoxygenation, the release of TM increased, and it became significantly higher at 120 min after reoxygenation compared with hypoxic incubation. The production of PGI2 significantly decreased during hypoxic incubation and further decreased within 30 min after reoxygenation, but returned to normoxic levels at 120 min after reoxygenation. In the Fura-2 release assay, a rapid and significantly greater release of Fura-2 was observed in hypoxia/reoxygenation compared with hypoxic incubation. In the 51Cr release assay which demonstrates cell death, 51Cr release did not increase in hypoxia/reoxygenation. CONCLUSIONS: The present study suggests that 120 min of hypoxia/reoxygenation induces endothelial dysfunction of ECs but does not cause cell death.

Cell Death↗

Expression of Fas in renal cell carcinoma.

We have investigated whether the Fas-mediated cell death pathway is functional in renal cell carcinoma. The expression of Fas in surgical specimens and cell lines of renal cell carcinoma was examined. Fas expression was positive in six out of 18 tumors measured by flow cytometry and was prominent in advanced tumors. Three out of the six Fas-positive tumors had already metastasized at the time of surgery. A significant correlation was found between the tumor volume and the percentage of Fas-positive cells in a tumor (r = 0.70, P = 0.0007). Fas-positive tumors were larger than Fas-negative tumors [mean tumor volume (ml) +/- SD, Fas(+), 265.6 +/- 136.8; Fas(-), 65.8 +/- 80.9, P = 0.0012]. All human renal carcinoma cell lines tested (ACHN, Caki-1, SMKT-R-2, SMKT-R-3 and SMKT-R-4) expressed Fas abundantly, as Fas-positive cells accounted for > 50% in all cell lines by flow cytometry. Treatment with anti-Fas antibody caused apoptosis in Fas-positive renal cell carcinoma cell lines. However, the effectiveness of apoptosis induction in individual cell lines was not correlated with the level of Fas expressed. These data suggest that Fas targeting may be a therapeutic option for treatment of advanced renal cell carcinoma which is refractory to either chemotherapy or irradiation.

Apoptosis↗

Subcellular distribution of rat liver NADPH-2,4-dienoyl-CoA reductase.

The subcellular distribution of 2,4-dienoyl-CoA reductase (EC. 1.3.1.34, DCR) in rat liver was studied biochemically and immunochemically after the induction of clofibrate. DCR activity was mainly detected in the mitochondrial fraction by sucrose density gradient centrifugation in the livers of both normal and clofibrate-treated rats. It was also shown that the polyclonal antibody against purified DCR detected the enzyme in the mitochondrial fraction. However, the antibodies, which were affinity purified using the purified mitochondrial DCR or were epitope-selected using the fusion-polypeptide expressed from the mitochondrial cDNA clone (lambda gt11-RDR181), were cross-reacted with the peroxisomal DCR. These results suggest that peroxisomal DCR is immunochemically indistinguishable from mitochondrial DCR.

Animals↗