PubMed Health⌕ Search

Biomedical subjects

T Yamano

Publications and source records attributed to T Yamano.

At least 19 recordsLinked to original sources
PubMed1997

Age-dependent susceptibility in mumps-associated hydrocephalus: neuropathologic features and brain barriers.

Central nervous system susceptibility to viral infection is often age dependent for unclear reasons. In this study, we examined the age-dependent susceptibility of the brain in mumps virus-induced hydrocephalus in hamsters, and evaluated the relationship between neuropathologic features and brain barriers using glial fibrillary acidic protein and zonula occludentes 1 (ZO-1) immunohistochemistry. In a group intracerebrally inoculated with mumps virus at 2 days of age, pathologic findings such as periventricular edema, ependymal cell loss, and ventricular dilation were more prominent and the distribution of mumps virus antigen was wider than in a group inoculated at 30 days of age. ZO-1-immunoreactive tight junctions in the hydrocephalic brains of the 2-day group were severely damaged in the choroid plexus and ependyma, and in white matter capillaries as early as 3 days after inoculation. These changes were not apparent in the hydrocephalic brains of the 30-day group. Prominent cortical dissemination of virus in the 2-day group was related to underdeveloped perivascular glial foot processes in brain parenchyma. Periventricular edema in the 2-day group was linked to ependymal and blood-brain barrier tight-junction permeability. Our results suggest that tight junctions in the early postnatal period are more immature and fragile than in the adult. We concluded that brain susceptibility in mumps virus-induced hydrocephalus is intimately related to the maturity of brain barriers.

Aging↗
PubMed1996

Dissociation of DDVP-induced DNA strand breaks from oxidative damage in isolated rat hepatocytes.

Dichlorvos (DDVP)-induced DNA single strand breaks were investigated in isolated rat hepatocytes. In a dose-response study in hepatocytes from PB-treated rats (80 mg/kg i.p., for 3 days), 250 microM DDVP substantially reduced cellular non-protein sulfhydryl (NPSH) content, but had no detectable effect on DNA. At 500 microM, the increase in DNA single strand breaks was significant, with a slight increase in cellular lipid peroxidation. At doses over 1000 microM DDVP, cell death was accompanied with considerable lipid peroxidation, and DNA single strand breaks were evident. When the antioxidant N,N'-diphenyl-p-phenylene diamine (DPPD) was added or if the hepatocytes were incubated under air instead of 95% O2, lipid peroxidation and cell death were attenuated but DNA single strand breaks and reduction in NPSH content were not. On the other hand, ferrous iron-induced DNA single strand breaks, lipid peroxidation, and depletion of NPSH content were all attenuated by DPPD or by incubating the cells under air. With respect to the subcellular lipid peroxidation, DDVP caused a significant increase mainly in the microsomal fraction, whereas ferrous iron caused rapid and substantial increases in mitochondrial, microsomal, and nuclear fractions. There were more DNA single strand breaks caused by N-nitrosodiethylamine (NDEA), which becomes genotoxic after microsomal metabolism, in hepatocytes from PB-treated rats than in those from control rats. The number of these breaks was reduced by adding the cytochrome P450 inhibitor metyrapone. On the other hand, the effect of DDVP on DNA was not affected by modification of the cytochrome P450 status. These results suggest that lipid peroxidation induced by DDVP in isolated rat hepatocytes plays a significant role in its cytotoxicity but not in its genotoxicity.

Animals↗
PubMed1996

A novel nonsense mutation in exon 1 and a transition in intron 3 of the lipoprotein lipase gene.

We examined the lipoprotein lipase (LPL) gene by single strand conformation polymorphism (SSCP) and by restriction fragment length polymorphism (RFLP) analysis in 106 patients with hypertriglyceridemia to screen for novel mutations and to study the contribution of LPL genetic defects in hypertriglyceridemia. We found a single incidence of a homozygous novel nonsense mutation (216G-->A; -14Tryptophan-->stop codon) in exon 1 and 6 cases heterozygous for a single transition (C-->T) at six bp upstream from splicing acceptor site of intron 3. These mutations were not found in 105 normolipidemic controls. The proband homozygous for the nonsense mutation in exon 1, a 74 year old woman, had mild hyperchylomicronemia and her post-heparin plasma showed no LPL protein. However, four heterozygous among family members did not demonstrate hypertriglyceridemia. The frequency of heterozygosity for the C-->T transition in intron 3 was significantly different from that in normolipidemic controls. Therefore, it was suggested that the mutation is involved in hypertriglyceridemia. All of the heterozygotes were men with 4 patients having impaired glucose tolerance or diabetes mellitus. These observations suggest that this polymorphism in intron 3 combined with other as yet undefined factors may be related to hypertriglyceridemia.

Adult↗
PubMed1996

[Clonal analysis of hepatocellular carcinoma].

We investigated the cell clonality of 12 cases of female solitary hepatocellular carcinoma (HCC) that were associated with hepatitis virus infection. The clonal origin of HCC could be assessed by the method based on restriction fragment length polymorphism (RFLP) of X-chromosome-linked androgen receptor gene (AR) and phosphoglycerate kinase (PGK) gene, taking advantage of random inactivation of one of two X-chromosomes by methylation in females. We extracted DNA samples from both fresh and paraffin-embedded specimens of the same lesion as a source of DNA sample for polymerase chain reaction (PCR). Consequently, it was possible to use methylation-sensitive restriction enzymes and PCR to study differential methylation patterns among alleles of these genes for both DNA samples. The RFLPs of AR gene and PGK gene were found in eight of 12 cases and five of 12 cases, respectively. There were two cases which had no RFLPs in either AR gene or PGK gene. All cases of HCC which had RFLP in either AR gene or PGK gene demonstrated monoclonal origin of the tumor regardless of their histologic patterns.

Aged↗
PubMed1995

The adverse effects of oral 2-mercaptobenzimidazole on pregnant rats and their fetuses.

The effects of oral 2-mercaptobenzimidazole (2-MBI) on pregnant Wistar rats were examined. In a preliminary dose-finding study, pregnant rats treated with 2-MBI over Days 7-17 of gestation showed reduction in maternal thymus weights with compound-related mortality at doses > or = 40 mg/kg. No adverse effects on fetuses were found at doses < or = 40 mg/kg. However, anasarca, cleft palate, and dilated lateral ventricles were present in all fetuses from the only survivor among the dams treated with 60 mg/kg of 2-MBI. In the teratology study, pregnant rats were treated with 2-MBI at doses of 0, 3.3, 10, and 30 mg/kg during the period of organogenesis (Gestation Days 7-17). In addition, pregnant rats of three groups were also treated with 60 mg/kg of 2-MBI for 3 or 4 days during specific periods of organogenesis (Days 7-10, 11-14, or 15-17 of gestation). Treatment on Gestation Days 7-17 resulted in reduced maternal thymus weights at doses of > or = 3.3 mg/kg. In addition to reduced fetal weights, visceral variations (kinked ureter and dilated renal pelvis) and delayed ossification were seen in the fetuses at doses > or = 10 mg/kg, and skeletal variations (rudimentary lumbar ribs) were seen at 30 mg/kg. In the fetuses from the dams treated with 60 mg/kg of 2-MBI, rudimentary lumbar ribs were seen mainly in the group treated on Days 7-10 of gestation, whereas kinked ureter and dilated renal pelvis were evident mainly in the group treated on Gestation Days 15-17.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗
PubMed1995

Effects of pesticides on isolated rat hepatocytes, mitochondria, and microsomes II.

Twenty-two pesticides were examined in vitro for their effects on hepatocytes, mitochondria, and microsomes isolated from male rats. Twelve pesticides reduced non-protein sulfhydryl (NPSH) content in hepatocytes to less than 80% of control at a concentration of 10(-3) M. Chlorothalonil and ziram were especially effective, reducing NPSH content at 10(-4) M after 90 min incubation. Among those pesticides, only copper terephthalate and chlorothalonil were reactive with glutathione non-enzymatically and enzymatically, respectively. Lipid peroxidation in hepatocytes was stimulated by four pesticides, namely, chlorothalonil, pretilachlor, ethoprofos, and metribuzin at 10(-3)-10(-4) M. Cell viability was considerably decreased following incubation with chlorothalonil, trichlamide, and ziram. Hepatotoxicity of trichlamide was considered to be associated with its direct adverse effects on mitochondrial energy production, since it uncoupled isolated mitochondrial respiration at 10(-6) M and depleted cellular ATP content prior to cell death. Conversely, chlorothalonil- and ziram-induced hepatotoxicity seemed to be related to their depleting effects on cellular sulfhydryls, since addition of the thiol compound dithiothreitol to the hepatocytes incubation mixture protected cells. With respect to isolated mitochondrial respiration, four pesticides inhibited state 3 and/or state 4 respiration rates at 10(-3)-10(-4) M, whereas seven pesticides uncoupled state 4 respiration at 10(-3)-10(-6) M. With respect to isolated microsomal lipid peroxidation, three pesticides were peroxidative at 10(-3)-10(-4) M, whereas three pesticides were antioxidative at 10(-3)-10(-7) M. Only two pesticides, beta-endosulfan and metalaxyl, had essentially no effects on any parameters tested at 10(-3) M.

Animals↗
PubMed1995

[Mechanism on formation of new ipsilateral corticospinal tract following neonatal unilateral cortical ablation in rats].

The corticospinal tract in the rat after neonatal ablation of the unilateral cerebral cortex was studied morphologically using the antegrade horse-radish peroxidase (HRP) tracing method. An aberrant ipsilateral tract was observed 7 days after the operation. Formation of the aberrant neuronal pathway has been confirmed to be contributed mainly by new axons, which ramified at the level of the pyramidal decussation from healthy corticospinal fibers. This ramified axon ran toward the ipsilateral dorsal funiculus. A few fibers also contributed to the aberrant pathway by changing their direction on the way of extension at the level of the pyramidal decussation. These results indicate that the ramification and change of the direction of extending axons play an important role for formation of a new ipsilateral corticospinal tract.

Animals↗
PubMed1994

Pathogenesis of cerebellar deformity in experimental Chiari type I malformation caused by mumps virus.

We sought to elucidate the pathogenesis of Chiari type I malformation using an experimental model of hydrocephalus produced by inoculating hamsters with mumps virus. Dilatation of the lateral ventricules was detected in all brains inoculated at 2, 10, and 25 days of age. The cerebellum in hamsters inoculated at 2 and 10 days of age showed elongation and flattening of the vermis and protrusion or notching of the uvula. All layers, i.e., the molecular, Purkinje cell, and granular layers, and the white matter were preserved, but had become narrow. Purkinje cells remained normal. Hamsters inoculated at 25 days of age did not develop the cerebellar deformity. Mumps virus antigen was detected in all ependymal cells and in some epithelial cells of the choroid plexus in all hamsters that had been inoculated at 2, 10, or 25 days of age. Results suggest that Chiari type I malformation is caused by two main factors occurring simultaneously, i.e., increasing intracranial pressure and rapid histogenesis of the cerebellar cortex.

Animals↗
PubMed1994

Histochemical study of mitochondrial enzymes in cerebellar cortex of macular mutant mouse, a model of Menkes kinky hair disease.

The cerebellar Purkinje cells in the hemizygote of the macular mutant mouse contain numerous abnormal mitochondria which show a marked decrease in cytochrome c oxidase activity. Using histochemical methods we studied the activity of other mitochondrial enzymes, such as NADH diaphorase and succinic dehydrogenase, in the cerebellar cortex of this mutant mouse. Such activities were markedly increased in the Purkinje cells, especially in the soma and stem dendrite, from 10 days after birth in the hemizygote as compared with findings in normal littermates. These results were considered to be due to an increased number of abnormal mitochondria.

Animals↗
PubMed1994

Effects of TRI-n-butyl phosphate on pregnancy in rats.

A teratological study was carried out on the plasticizer tri-n-butyl phosphate (TBP). Pregnant Wistar rats were treated orally on days 7-17 of gestation with TBP at 0, 100, 200, 400 or 800 mg/kg/day in the dose-finding study and 0, 62.5, 125, 250 or 500 mg/kg/day in the subsequent teratological study. Caesarean sections were performed on day 20 of gestation. In the dose-finding study, all of the pregnant rats were killed by the treatment with TBP at 800 mg/kg/day. In the teratological study, salivation and depression of body weight gain, adjusted body weight gain and food consumption were observed at the higher doses of TBP. There were no significant differences between the groups in the incidence of dead or resorbed foetuses, the number of living foetuses and the body weights of living foetuses of both sexes. The incidence of rudimentary lumbar rib increased significantly at 500 mg/kg/day. There were two cases of malformation: a foetus with deformity of fore- and hind-limbs at 400 mg/kg/day in the dose-finding study and conjoined twins exhibiting three fore-limbs and four hind-limbs at 125 mg/kg/day in the teratological study. These malformations were rare in the background data of teratology, and the incidence of foetuses with malformations was not increased significantly. Therefore, TBP was considered not to be teratogenic in this study.

Administration, Oral↗
PubMed1994

Low levels of serum apolipoprotein A I and A II in senile dementia.

We studied the serum lipoprotein and apolipoprotein profiles in 44 patients with sporadic late-onset Alzheimer's dementia and 43 patients with vascular dementia. The levels of high-density lipoprotein (HDL) cholesterol were lower in both patient groups than in a control group. Apolipoprotein A I and A II levels have decreased in both the patient groups, especially in the vascular dementia group. The HDL-cholesterol levels correlated positively with the level of apolipoprotein A I, but not with the level of apolipoprotein A II. The ratios of apolipoprotein A I/A II have increased in both the patient groups. The apolipoprotein A II levels have disproportionally decreased in the patient groups. The serum apolipoprotein A II may involve the pathological process in the patients with senile dementia.

Aged↗
PubMed1994

A new protocol and criteria for quantitative determination of sensitization potencies of chemicals by guinea pig maximization test.

This paper presents precise sensitization test data of 15 chemicals with a wide spectrum of sensitization potencies, and proposes a new protocol and criteria for quantitative evaluation of sensitization potencies of chemicals. The tests were performed according to the design of Magnusson and Kligman, changing the application concentrations for induction as well as for challenge phases. 3-dimensional relationships between mean response (or sensitization rate), induction and challenge concentrations were found in all chemicals tested. The following 2 values are proposed as a quantitative measure of sensitization potency: (a) the minimum induction concentration that induces a positive response; (b) the challenge concentration that induces a mean response approximately equal to 1.0 among the animals applied with the highest concentration for induction. Both values coincided with each other within the range of 1 order of magnitude in every compound except 2. The values varied by 5 orders or more of magnitude among the compounds, showing a wide variation of sensitization potencies among chemicals. A good correlation was found for every chemical between the value of sensitization potency thus obtained and the residual levels in causative products in human cases of allergic contact dermatitis. A new experimental protocol for obtaining values (a) and (b) is proposed.

Allergens↗
PubMed1994

Copper distribution in fetus and placenta of the macular mutant mouse as a model of Menkes kinky hair disease.

Menkes kinky hair disease (MKHD) in humans is caused by a disturbance in copper homeostasis. A mutant mouse shows clinical and biochemical features very close to MKHD. In an attempt to elucidate the defect in copper transport, the copper distribution in various organs of 18-gestational-day-old macular mouse embryos, following administration by a single injection of saline (control) or 50 micrograms of CuCl2 on day 16 of gestation or by two injections on days 15 and 17 of gestation to the dams, was examined both biochemically and histochemically. The copper content in the hemizygous fetus (Ml/y) born to the homozygous mother, who had no copper injection during gestation, was lower in the brain and liver but higher in the placenta than in the respective organs of the normal fetus. When 50 micrograms of CuCl2 was injected into heterozygous dams (Ml/+) on day 16 of gestation, their hemizygous fetuses showed a slight increase in the copper content in the brain and liver, but the amount of copper in these organs was still less than that of the normal fetus. Conversely, the copper content in the placenta of the hemizygous fetus was far higher than that of the normal fetus. In the copper staining of the fetuses harvested from heterozygous dams, some fetuses showed copper deposition in the placenta, but not in the liver. The others showed no copper deposit in both the placenta and liver, thus indicating that the former were hemizygous for the mutation and the latter were normal littermates.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Experimental hydrocephalus induced by intraplacental mumps virus inoculation].

Experimental production of congenital hydrocephalus was undertaken by inoculating mumps virus into pregnant hamsters intravenously or intraplacentally. When the mumps virus was inoculated intravenously on the 8th, 10th, 12th, or 14th day of gestation, some fetuses were aborted and those which could come to term did not develop hydrocephalus after birth. Offsprings from the mothers, which had had intraplacental inoculation on the 14th day of gestation, showed ventricular dilatation in about 28%. Histological examination revealed inflammatory infiltration on the surface of ependymal layers, subependymal edema and microglial activation in the underlying ependyma of the aqueduct. These findings were thought to have resulted from ependymitis caused by mumps virus. The transplacental infection of mumps virus is considered to be extremely rare. However, in such conditions as the placental barrier is impaired, mumps virus will possibly pass through the placenta, and will cause hydrocephalus to the infant.

Animals↗