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Biomedical subjects

K Chiba

Publications and source records attributed to K Chiba.

At least 523 records · Page 29Linked to original sources
PubMedDate not supplied

Neonatal mouse hip joint and hindlimb anomalies induced by prenatal exposure to Ara-C.

To induce hip joint anomalies and assess their relationship with hindlimb anomalies, pregnant mice (Jcl;ICR) were injected intraperitoneally with a single dose of 5.0 or 7.5 mg/kg of cytosine arabinoside (Ara-C) on dg 8, 9.5, or 11. On the 24th postnatal day, surviving offspring were stained by alizarin red S and anomalies were observed. Hip joint anomalies were observed only in one group exposed to 7.5 mg/kg on dg 9.5; the incidence of the hip joint anomalies in this group was about 30%. The types of hip anomalies observed were femoral shaft dysplasia, pseudoarthrosis of the femur, femoral head dysplasia, acetabular dysplasia, fusion between the femoral head and acetabulum, and pseudoarthrosis of the coxal bone. All of these anomalies were associated with preaxial hyperplasia of the hind paws and lower leg anomalies. Strangely, while newborns with no hip joint anomalies had a fairly high rate of oligodactyly, no newborn with hip joint anomalies had oligodactyly.

Animals↗
PubMedDate not supplied

Immunosuppressive activity of FTY720, sphingosine 1-phosphate receptor agonist: I. Prevention of allograft rejection in rats and dogs by FTY720 and FTY720-phosphate.

FTY720, a new class of immunomodulator, induces lymphopenia by sequestration of circulating lymphocytes into secondary lymphoid tissues. FTY720 at 0.1 to 1 mg/kg significantly prolonged the allograft survival in a dose-dependent manner and showed a marked synergistic effect in combination with cyclosporine (CsA) in rat skin and cardiac allograft models. In addition, the canine renal allograft survival was significantly prolonged by combination therapy with FTY720 at 0.03 to 1 mg/kg and CsA at 10 mg/kg as compared with monotherapy of FTY720 or CsA. By contrast, the combination therapy with CsA and azathioprine or CsA and mycophenolate mofetil resulted in only an additive effect in rat skin allograft. When FTY720 was administered to rats, FTY720 was metabolized by omega-oxidation of the octyl side chain, and beta-oxidation subsequently, or phosphorylated by sphingosine kinase. Omega- and beta-oxidized 4 metabolities of FTY720 at 10 mg/kg i.v. showed neither lymphopenia nor immunosuppressive activity in rat skin allograft. On the other hand, (S)-enantiomer of FTY720-phosphate at 0.1 and 1 mg/kg intravenously induced a marked lymphopenia and significantly prolonged the allograft survival in the rat allotransplantation. From these results, it is suggested the lymphopenia and the immunosuppression induced by FTY720 administration is due to the agonistic activity against SIP receptors of the active metabolite, (S)-FTY720-phosphate.

Animals↗
PubMedDate not supplied

Baseline level of blood lead concentration among Japanese farmers.

Lead concentrations were determined for more than 2500 blood samples (more than 2000 winter samples and approximately 500 summer samples) collected from farmers in various parts of Japan to establish reliable baselines for blood lead levels; the analysis was conducted in a single laboratory to avoid any inter-laboratory errors. Blood lead levels distributed log-normally with a geometric mean (i.e., a geometric standard deviation) of 48.6 micrograms/L (1.51) for males and 32.1 micrograms/L (1.50) for females. The levels observed were among the lowest in the industrialized countries of the world. The sex difference was significant (P less than .01) while the difference in Pb-B between winter and summer was essentially insignificant. Both drinking and smoking habits were associated with a dose-dependent increase in blood lead levels, especially in males; the increment was additive when the examinee was a drinker-smoker. The geographical difference in blood lead levels remained inconclusive.

Adult↗
PubMedDate not supplied

CT demonstration of calcification within old cerebral infarcts.

Calcifications within old cerebral infarcts were demonstrated by CT in three patients who had suffered strokes probably due to emboli from a carotid or cardiac source. In two of them, calcifications were not shown on CT at onset but were first noted on follow-up CT approximately 2 years later in one, and 5 years later in the other. In the third case a large solitary calcification was found on the first CT carried out 13 years after onset. To our knowledge, these findings have not been described previously.

Brain Diseases↗
PubMedDate not supplied

Bifidobacterium-fermented soy milk extract stimulates hyaluronic acid production in human skin cells and hairless mouse skin.

We examined the effects of Bifidobasterium-fermented (BE) and nonfermented (SME) soy milk extracts on the production of hyaluronic acid (HA) in vitro and in vivo. BE, but not SME, significantly enhanced the production of HA in monolayer and organotypic cultures of human keratinocytes, in cultures of human skin fibroblasts, and in hairless mouse skin following topical application for 2 weeks. In the organotypic cultures formed by a similar structure to human epidermis, BE also extended the distribution of HA. Genistein and daidzein, known to stimulate HA production, were detected in BE at a concentration of 0.18 and 0.07 mM, respectively, but not in SME. Therefore, BE has the potential to enhance HA production in the epidermis and dermis, mainly due to genistein released from its glycoside during fermentation. BE is expected to prevent the age-dependent loss of cutaneous HA.

Administration, Cutaneous↗
PubMedDate not supplied

Characteristics of skin wrinkling and dermal changes induced by repeated application of squalene monohydroperoxide to hairless mouse skin.

We have studied the effect of squalene monohydroperoxides (Sq-OOH), initial products of UV-peroxidated squalene, on the skin of hairless mice. Repeated topical application of 10 mM Sq-OOH to hairless mice for 15 weeks induced definite skin wrinkling. When image analysis was used to compare wrinkle formation induced by ultraviolet B (UVB) irradiation and Sq-OOH treatment, the degree of wrinkling in exposed skin was seen to be similar. However, the characteristics of wrinkles induced by either method differed markedly with regard to direction and distribution. Biochemical analysis revealed a significant decrease in collagen content per unit area and mass in Sq-OOH-treated skin, whereas no changes per unit area and decrease in collagen per unit mass were observed in UVB-irradiated skin. As for glycosaminoglycan (GAG) content per unit area, significant increases were observed in both Sq-OOH-treated skin and UVB-irradiated skin. These changes were not induced by organic hydroperoxides such as TERT-butylhydroperoxide or cumene hydroperoxide treatment. Histological observation revealed epidermal hyperplasia and dermal alterations such as collagen degradation and GAG increases in Sq-OOH-treated skin. Histological changes induced by Sq-OOH were not as pronounced as those induced by UVB irradiation. These results clearly suggest that the wrinkling and changes in dermal collagen content induced by Sq-OOH are qualitatively different to those induced by UVB exposure. This may provide a useful model for the study of skin aging, particularly with regard to collagen content.

Administration, Topical↗
PubMedDate not supplied

Steady-state pharmacokinetics of phenytoin from routinely collected patient data.

Previously reported routine phenytoin clinical pharmacokinetic data from Japan, England, and Germany were analysed to estimate population pharmacokinetic parameters. There were 780 steady-state phenytoin concentrations and associated dosage rates (mg/day) from 322 patients. The patient group spanned paediatric and adult ages, mean age being 18.4 +/- 17.3 (SD) years; 53% were males. The data were analysed using NONMEM, a computer programme designed for population pharmacokinetic analysis. Estimates of the influence of age, gender, data source, height and weight on the maximum elimination rate (Vm) and Michaelis-Menten constant (Km) were obtained. The Vm and Km of a 70 kg adult male European were estimated to be 415 mg/day and 5.7 mg/L, respectively. Vm is not influenced by gender, age or data source. The parameters of a power function of height and weight were estimated to adjust Vm for body size. The best function adjusts Vm in proportion to weight to the 0.6 power; height contains no useful information. Km is not influenced by gender. The Km for patients less than 15 years old is 43% less than that of older patients. The Km of Japanese patients appears to be 23% less than that for European patients. Even after adjustments for age, etc., apparent Vm and Km vary unpredictably among individuals with a coefficient of variation between 10 to 20% and approximately 50% respectively.

Adolescent↗
PubMedDate not supplied

Predictive indicators of successful varicocele repair in men with infertility.

OBJECTIVE: We sought predictive indicators of functionally successful repair in 168 infertile Japanese males who underwent high ligation of a varicocele via a retroperitoneal approach. METHODS: Possible indicators evaluated included age at marriage, duration of infertility, testicular volume, varicocele grade, seminal analysis findings, and serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and testosterone. All patients had palpable or visible unilateral left varicoceles. Success in conception was evaluated in all subjects 1 year after varicocele repair. RESULTS: No associations were observed between outcome and mean age at marriage, infertility duration, varicocele grade, seminal volume, or serum PRL and testosterone concentrations, but testicular volume, sperm count, percentage of motile sperm, and serum FSH and LH concentrations were significantly associated with outcome. Multiple regression analysis of dependence of outcome revealed testicular volume and serum FSH concentrations to be independent predictors. CONCLUSIONS: Varicocele repair is likely to accomplish fertility in patients with a combined testicular volume of at least 30 mL or serum FSH concentrations lower than 11.7 mIU/mL.

Adult↗