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T Yamauchi

Publications and source records attributed to T Yamauchi.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effects of rat ventral and dorsal hippocampus temporal inactivation on delayed alternation task.

To determine the involvement of the hippocampal regions in a operant-type delayed alternation task of short delay or long delay, microinjections of muscimol into the hippocampus were used for temporal inactivation during the behavioral test in each rat. Dorsal hippocampal inactivation impaired the correct ratio of long delay. Ventral hippocampal inactivation showed no changes in the correct ratio, however, it increased the tendency of perseveration in long delay. These findings suggest hippocampus has regional differentiation in delayed alternation task.

Animals↗
PubMed2001

Physical activity and subsistence pattern of the Huli, a Papua New Guinea Highland population.

Several studies on human energetics have been conducted in developed and developing countries, but very few simultaneously measured time use and energy expenditure. Only a few quantitatively compared subsistence patterns between rural and urban dwellers of an identical population. Here we present the daily physical activity level (PAL), physical exertion, time, and energy expenditure in contrasting subsistence/occupational activities of Papua New Guinea Highlanders, comparing 27 rural villagers (15 men, 12 women) who maintained traditional subsistence agriculture, with 29 urban migrants (14 men, 15 women) who engaged in cash-earning work. A large sex inequality in the division of labor was noted between rural males and females, but not among urban dwellers. Rural-urban comparison indicated sex differences in urbanization. For urban men, the reduction of physical exertion level during work, from energy-consuming agricultural work to sedentary cash-earning work, together with significantly extended work time (by 261 min/day, P < 0.001), led to an increase in work energy expenditure (15-29% of PAL). In contrast, urban women who spent almost equal time at work relative to rural women showed a lower energy expenditure (18% compared to 26% of PAL). The associations with urbanization included a gain in body weight (by 6.4 kg for either sex) and reduced PAL (by 7%, not significant in men; 13%, P < 0.01 in women). Further research is needed to elucidate the effects of urbanization on time use, energy expenditure, and PAL, by comparing rural residents with urban migrants in the same population.

Adult↗
PubMed2001

Differences in paired-pulse facilitation and long-term potentiation between dorsal and ventral CA1 regions in anesthetized rats.

To clarify hippocampal regional differences in synaptic plasticity, paired-pulse facilitation (PPF, a form of short-term plasticity), long-term potentiation (LTP, a form of long-term plasticity), and their interactions were studied in the dorsal and ventral hippocampal CA1 regions of anesthetized rats. Baseline PPF and post-LTP PPF experiments were conducted at interstimulus intervals (ISIs) of 20-320 ms. A general protocol (100 Hz, 1 s) and a stronger protocol (250-Hz pulse series) were applied for LTP induction. PPF were observed in both regions; however, the degree was lower and the range of ISIs was narrower in the ventral region compared with the dorsal region. The degree of ventral LTP was lower than that of the dorsal LTP. The interaction between PPF and LTP was observed in both regions (PPF change correlated inversely with degree of baseline PPF). However, this was also different in each region. Dorsal PPF increased or decreased; in contrast, ventral PPF of short ISIs after LTP only decreased. These regional differences in short-term and long-term synaptic plasticity may explain a consequence of different afferent inputs and information processing.

Animals↗
PubMed2001

Does the polymorphism of cytochrome P-450 2E1 affect the metabolism of N,N-dimethylformamide? Comparison of the half-lives of urinary N-methylformamide.

The aim of this study was to clarify whether phenotypic variation exists when subjects with different genotypes of cytochrome P450 2E1 (CYP2E1) are exposed to N,N-dimethylformamide (DMF). The genotypes of CYP2E1 were confirmed in 123 healthy male volunteer subjects. Of the 123 subjects, the numbers of c1 homozygotes, c2 heterozygotes, and c2 homozygotes were 77, 45, and 1, respectively. Seven of the c1 homozygotes, five of the c2 heterozygotes, and the one c2 homozygote (mean age: 22.7 years, range: 20-27 years) were exposed to DMF vapor twice, once via the skin and once via the lung, for a total of 8 h per subject at a concentration below 10 ppm, the occupational exposure limit recommended by the Japan Society for Occupational Health, the American Conference of Governmental and Industrial Hygienists, and Deutsche Forschungsgemeinschaft, at 27 degrees C and 44% relative humidity. Exposure levels were 6.2+/-1.0 ppm in dermal exposure and 7.1+/-1.0 ppm in inhalation exposure. Urine samples were collected until 72 h after exposure. The half-lives of urinary N-methylformamide (NMF) were obtained as the phenotype. The average urinary NMF half-lives of the c1 homozygotes, the c2 heterozygotes, and the c2 homozygote were 3.86+/-1.90, 4.38+/-1.53, and 4.2 h after dermal exposure, and 1.58+/-0.42, 1.84+/-0.61, and 3.2 h after respiratory exposure. The NMF half-lives of the c1 homozygotes were not significantly different from those of the c2 heterozygotes, and there were no differences between the NMF half-lives on the subjects with and without the c2 allele. Even though the data were obtained from only one c2 homozygote, it is noteworthy that the NMF half-life of this subject was slightly less than that of the c1 homozygotes after respiratory exposure.

Administration, Cutaneous↗
PubMed2001

N,N-dimethylformamide: significance of dermal absorption and adjustment method for urinary N-methylformamide concentration as a biological exposure item.

OBJECTIVES: To clarify the potential for dermal absorption of N,N-dimethylformamide (DMF) (CAS No. 68-12-2) vapor, and the appropriate adjustment method and the half-lives of urinary concentrations of N-methylformamide (NMF) as the biological exposure item of DMF. METHODS: Thirteen healthy male volunteers (mean age: 22.7 years, range: 20-27) were exposed to DMF vapor twice, via both the skin and the lung, for 4 h at concentrations below 10 ppm, the recommended occupational exposure limit set by the Japan Society for Occupational Health, the American Conference of Governmental and Industrial Hygienists, and Deutsche Forschungsgemeinschaft, under conditions of 27 degrees C and 44% humidity. Each volunteer was exposed to DMF via the skin in a whole-body type exposure chamber and outside the chamber, via the lung by a respirator connected to the chamber. Exposure levels were 6.2 +/- 1.0 ppm in dermal exposure and 7.1 +/- 1.0 ppm in inhalation exposure. Urine samples were collected at every opportunity until 72 h after exposure; and NMF, as well as volume, creatinine, and specific gravity were measured. Dermal and inhalation intakes were compared after adjusting concentrations. RESULTS AND CONCLUSIONS: DMF vapor absorptions via the skin and the lung were estimated to be 40.4 and 59.6%, respectively. Workers need to be aware of the risk of dermal absorption of DMF vapor as well as of the liquid. Though NMF concentrations adjusted by creatinine, specific gravity, and urinary volume showed good correlation with total NMF excretion and the absolute amount of NMF at each sampling time, creatinine-adjusted NMF concentration correlated better than the others. The biological half-life of urinary NMF after dermal exposure, 4.75 +/- 1.63 h, was longer than that after respiratory exposure, 2.42 +/- 0.63 h.

Adult↗
PubMed2001

Insertion polymorphism of CYP2E1 and urinary N-methylformamide after N,N- dimethylformamide exposure in Japanese workers.

OBJECTIVES: This study examined whether consideration of the *1C/*1D CYP2E1 insertion polymorphism is important for interpreting the biological monitoring of exposure to N,N-dimethylformamide (DMF) in Japanese workers. METHODS: The insertion genotype, airborne DMF exposure on the last day of a work week, and NMF in urine sampled just after the last workshift of the week were determined in 44 male and female Japanese workers. RESULTS AND CONCLUSIONS: The allelic frequency of this CYP2E1 polymorphism was 0.261 in this Japanese population of workers. The CYP2E1 insertion polymorphism did not contribute to NMF levels even after consideration of BMI or alcohol intake. The results indicate that CYP2E1 insertion polymorphism does not appear to be an important determinant for the interpretation of biological exposure to DMF by the measurement of urinary NMF.

Adult↗
PubMed2001

Neurohistochemical analysis of regeneration in rat peripheral nerve after end-to-side neurorrhaphy.

We investigated the regenerative capacity of motor nerves repaired by end-to-side or end-to-end neurorrhaphy, using choline-acetyltransferase (ChAT) activity measurement or histological analysis. The right medial gastrocnemius nerves (MGNs) of 62 male Fisher strain rats were transected and divided into three groups. In group 1, the distal ends of the MGN were coapted to the side of the lateral gastrocnemius nerve, using a Y-shaped silicone tube in end-to-side neurorrhaphy. In group 2, the nerve ends were reconnected by the traditional end-to-end technique. In group 3, the nerve ends were separated and remained unrepaired. The MGNs were sampled 1, 2, and 3 months postoperatively for histological examinations and ChAT activity measurement. The medial gastrocnemius muscle (MGM) was also sampled for histological evaluations. Axonal regeneration of MGN and the recovery of MGM to nearly normal histology and weight were observed in groups 1 and 2 3 months postoperatively. Although there were no significant differences in ChAT values between groups 1 and 2, the values were significantly larger than that of group 3 3 months postoperatively. These findings suggested that end-to-side neurorrhaphy would be an alternative treatment for peripheral nerve injury in certain clinical situations.

Animals↗
PubMed2001

Long-term follow-up of the clinical efficacy of chemotherapy for acute myeloid leukemia at a single institute.

A retrospective study was performed on 125 patients with de-novo acute myeloid leukemia (AML) who had received first remission induction therapy at Fukui Medical University Hospital in the 16 years between 1983 and 1998. For remission induction therapies, patients in the 1980s received mainly behenoylcytarabine (BHAC), 6-mercaptopurine (6-MP), and prednisolone (PSL), plus aclarubicin (ACR) or daunorubicin (DNR). Patients in the 1990s received mainly BHAC, 6-MP, and etoposide (VP-16) plus DNR or mitoxantrone (MIT) or idarubicin (IDA). Patients with hypoplastic bone marrow received low-dose cytarabine (Ara-C) therapy or cytarabine ocfosfate (SPAC). Since 1992, patients with French-American-British disease classification of M3 have received all-trans retinoic acid (ATRA) (+/-chemotherapy). In the 1990s, more intensified postremission therapy was performed compared with that done in the 1980s. The complete remission (CR) rate of all patients was 58%. Predicted 6-year overall survival (OS) and disease-free survival (DFS) rates in the CR patients were 22% and 28%, respectively. Multivariate analysis showed age and leukocyte counts as significant prognostic factors regarding CR, OS, and DFS rates. The CR and OS rates in the 1990s were improved significantly from those in the 1980s, at 69% versus 48% (P = 0.016), and 32% versus 15% (P = 0.0014), respectively. The early death rate, within 30 days, was decreased from 26% in the 1980s to 9% in the 1990s (P = 0.013). This decrease was thought to be the main cause of the high CR rate in the 1990s. However, DFS was not significantly improved. It is necessary to establish more effective postremission therapies in order to reduce the relapse rate and improve the prognosis.

Acute Disease↗
PubMed2001

Cryopreserved cultured epidermal allografts achieved early closure of wounds and reduced scar formation in deep partial-thickness burn wounds (DDB) and split-thickness skin donor sites of pediatric patients.

Burn treatment in children is associated with several difficulties, e.g. available skin replacement is small, donor area could expand, and subsequent hypertrophic scar and contracture could become larger along with their physical growth. In order to have better clinical results, the authors prepared cryopreserved cultured epidermal allografts from excess epidermal cells of other patients, and applied the epidermal allografts to 55 children, i.e. 43 cases of deep partial-thickness burn wounds (DDB) due to scald burn and 12 cases with split-thickness skin donor sites. In the 43 DDB patients, epithelialization was confirmed 9.1+/-3.6 days (mean+/-S.D.) after treatment. In 10 of the 43 patients, epithelialization was comparable between the area which received the epidermal allografts (grafted area) and the area which did not receive the epidermal allografts but was covered with usual wound dressing (non-grafted area). As a result, epithelialization day was 7.9+/-1.7 in grafted areas and 20.5+/-2.3 in non-grafted areas. In the 12 patients with split-thickness skin donor sites, epithelialization was confirmed 6.3+/-0.9 days after treatment. Epithelialization of the grafted and non-grafted areas was comparable in 8 of the 12 patients, and it was 6.5+/-1.1 days and 14.1+/-1.6 days, respectively. In these 10 DDB patients and 8 split-thickness skin donor site patients, redness and scar formation were also milder in the grafted area. The 55 patients have been followed up for 1-8 years (mean, 4.75 years), and scar formation was suppressed in both DDB and split-thickness skin donor sites. These findings showed that cryopreserved cultured epidermal allografts achieve early closure of the wounds and good functional outcomes.

Adolescent↗
PubMed2001

The role of nitric oxide and the renin-angiotensin system in salt-restricted Dahl rats.

To elucidate the role of nitric oxide (NO) and renin-angiotensin system (RAS) in the development of salt-sensitive hypertension, we investigated the pressor responses and renal histologic changes after long-term inhibition of endogenous NO synthesis in Dahl-Iwai salt-sensitive (DS) and salt-resistant (DR) rats under salt-re-stricted conditions that exaggerate RAS activation. Male DS and DR rats (6 weeks old) were fed with a low-salt (0.3%) diet for 5 weeks. NG-nitro-L-arginine (L-NA; dissolved in 60 mg/L deionized water), an arginine analogue acting as a NO-inhibitor, was also administered for 5 weeks. L-NA administration induced a gradual increase in systolic blood pressure (SBP) in both strains, and the pressor response in DS rats was apparently more enhanced relative to that in DR rats. Urinary nitrate plus nitrite (u-NOx) excretion was decreased by L-NA, with a significant negative correlation between SBP and u-NOx excretion in DS rats but not in DR rats. Plasma renin activity and urinary aldosterone level were significantly increased in L-NA-treated DS rats on week 5. Marked histologic changes with glomerular sclerosis and increased proteinuria and urinary N-acetyl-beta-glucosaminidase excretion were found in L-NA-treated DS rats but not DR rats. Competitive RT-PCR of mRNA extracted from the glomeruli revealed that angiotensin II type 1 receptor (AT1R) mRNA level was significantly lower in DS rats than in DR rats at week 2, and that L-NA administration significantly reduced glomerular AT1R level of DS rats at week 5, possibly because of downregulation. Our results showed that, even under sodium restriction, the pressor response and renal injury induced by chronic NO inhibition were markedly more enhanced in DS rats than in DR rats, which indicates that depletion of NO participates in both the development of hypertension and glomerular injury in DS rats through a potential activation of RAS irrespective of sodium loading. These data suggest that endogenous NO is an essential determinant of salt-sensitive hypertension in DS rats.

Aldosterone↗
PubMed2001

Investigation of the Ca(2+)-independent form of Ca(2+)/calmodulin-dependent protein kinase II in neurite outgrowth.

Neuronal Ca(2+)/calmodulin-dependent protein kinase II (CaM kinase II) plays important roles in the control of nerve functions in response to intracellular Ca(2+) (for reviews [Annu. Rev. Physiol. 57 (1995) 417-445; Trends Neurosci. 17 (1994) 406-412]). Brief Ca(2+) signals activate CaM kinase II, and stimulate an autophosphorylation of Thr-286 which allows the kinase to maintain its activated state even after the Ca(2+) concentration has returned to basal levels [J. Biol. Chem. 264 (1989) 16759-16763; Neuron 3 (1989) 59-70; J. Biochem. 109 (1991) 137-143]. Autophosphorylation of CaM kinase II occurs in situ, but it occurs relatively quickly, within just a few minutes [Endocrinology 134 (1994) 2245-2250; J. Biol. Chem. 268 (1993) 7863-7867; J. Biol. Chem. 265 (1990) 18055-18058]. In the present study, we investigated the involvement of the autophosphorylated/Ca(2+)-independent form of CaM kinase II in neurite outgrowth. When neuroblastoma Neruo2a (Nb2a) cells expressing the alpha isoform of CaM kinase II (Nb2a/alpha cells) were stimulated by plating, they formed neurites. The autophosphorylation of Thr-286 and appearance of Ca(2+)-independent activity preceded the neurite formation. The effect of mutating of the kinase autophosphorylation site replacing Thr-286 with Ala (alpha T286A kinase) or Asp (alpha T286D kinase) was examined. alpha T286A kinase was not converted to a Ca(2+)-independent form, and alpha T286D kinase had Ca(2+)-independent activity significantly as an autophosphorylated kinase. Cells expressing alpha T286D kinase had much longer neurites than Nb2a/alpha cells, whereas cells with alpha T286A kinase did not form neurites. These results indicated that the Ca(2+)-independent form of CaM kinase II autophosphorylated at Thr-286 is involved in neurite outgrowth.

Animals↗
PubMed2001

Lysyl oxidase-catalyzed cross-linking and insolubilization reactions of Lys-containing polypeptides and synthetic adhesive proteins.

The lysyl oxidase- (LO-) mediated insolubilization reactions of the Lys-containing polypeptides have been examined using poly(L-Lys) with degrees of polymerization (Dps) ranging 1 from 2300, copoly(LysxAlay) (x:y = 1:4, 1:3; 1:1, 2:1, and 3:1), copoly(LysxGlyy) (x:y = 1:1 and 2:1), and synthetic adhesive proteins with sequential repetitive units enriched in the Lys residues, poly(Ala-Lys-Pro-Ser-Tyr-Pro-Pro-Thr-Tyr-Lys), poly(Ala-Gly-Tyr-Gly-Gly-Ala-Lys), and poly(Gly-Gly-Gly-Tyr-Gly-Gly-Tyr-Gly-Lys). All of the substrates were insolubilized by the LO-catalyzed oxidation of the epsilon-amino group in the Lys residues. The Dps of the polypeptide substrates did not affect the kinetic constants, the Km and Vmax values. The Km and Vmax values and the insolubilization rates varied depending on the Lys contents in the substrate polypeptides, which were enriched in Gly and Ala residues. As the Lys content increased, the Km and Vmax values became lower and higher, respectively. The insolubilization rates decreased with increase of the Lys content. The time-dependent changes in the LO-catalyzed aldehyde production, the insolubilization, and remaining LO activity demonstrated that the cross-linking and the insolubilization steps occurred along with LO deactivation, indicating that the enzymatic and chemical processes in the LO-mediated insolubilization occur in order.

Adhesives↗
PubMed2001

Growth hormone signalling and apoptosis in neonatal rat cardiomyocytes.

Growth hormone (GH) has been reported to be useful to treat heart failure. To elucidate whether GH has direct beneficial effects on the heart, we examined effects of GH on oxidative stress-induced apoptosis in cardiac myocytes. TUNEL staining and DNA ladder analysis revealed that hydrogen peroxide (H2O2)-induced apoptosis of cardiomyocytes was significantly suppressed by the pretreatment with GH. GH strongly activated extracellular signal-regulated kinases (ERKs) in cardiac myocytes and the cardioprotective effect of GH was abolished by inhibition of ERKs. Overexpression of dominant negative mutant Ras suppressed GH-stimulated ERK activation. Overexpression of Csk that inactivates Src family tyrosine kinases also inhibited ERK activation evoked by GH. A broad-spectrum inhibitor of protein tyrosine kinases (PTKs), genistein, strongly suppressed GH-induced ERK activation and the cardioprotective effect of GH against apoptotic cell death. GH induced tyrosine phosphorylation of EGF receptor and JAK2 in cardiac myocytes, and an EGF receptor inhibitor tyrphostin AG1478 and a JAK2 inhibitor tyrphostin B42 completely inhibited GH-induced ERK activation. Tyrphostin B42 also suppressed the phosphorylation of EGF receptor stimulated by GH. These findings suggest that GH has a direct protective effect on cardiac myocytes against apoptosis and that the effect of GH is attributed at least in part to the activation of ERKs through Ras and PTKs including JAK2, Src, and EGF receptor tyrosine kinase.

Animals↗
PubMed2001

The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity.

Adiponectin is an adipocyte-derived hormone. Recent genome-wide scans have mapped a susceptibility locus for type 2 diabetes and metabolic syndrome to chromosome 3q27, where the gene encoding adiponectin is located. Here we show that decreased expression of adiponectin correlates with insulin resistance in mouse models of altered insulin sensitivity. Adiponectin decreases insulin resistance by decreasing triglyceride content in muscle and liver in obese mice. This effect results from increased expression of molecules involved in both fatty-acid combustion and energy dissipation in muscle. Moreover, insulin resistance in lipoatrophic mice was completely reversed by the combination of physiological doses of adiponectin and leptin, but only partially by either adiponectin or leptin alone. We conclude that decreased adiponectin is implicated in the development of insulin resistance in mouse models of both obesity and lipoatrophy. These data also indicate that the replenishment of adiponectin might provide a novel treatment modality for insulin resistance and type 2 diabetes.

Adiponectin↗
PubMed2001

Intravenous immunoglobulin prevents experimental autoimmune myositis in SJL mice by reducing anti-myosin antibody and by blocking complement deposition.

High-dose intravenous immunoglobulin (IVIG) therapy has been effective in many autoimmune and systemic inflammatory diseases including polymyositis (PM) and dermatomyositis (DM). In the present study we evaluated the efficacy of IVIG using experimental models of PM and DM. An experimental autoimmune myositis (EAM) model was produced in SJL/J mice by an immunization with rabbit myosin B (MB) fraction. In this model, the plasma level of anti-MB antibody was elevated, and mouse IgG and complement C3 were deposited in the muscle fibres. Administration of IVIG dose-dependently reduced the incidences of necrotic and inflammatory changes in the skeletal muscle. IVIG treatment also decreased the elevation of anti-MB antibody level, as well as the deposition of IgG and C3. We next evaluated the effect of IVIG in adoptive EAM mice made by an intravenous injection of lymph node cells previously stimulated with MB. Adoptive EAM mice showed similar lesions in skeletal muscle as EAM mice and IVIG inhibited the lesion development. In vitro experiments demonstrated that IVIG inhibited complement-mediated lysis of human erythrocytes sensitized with anti-human erythrocyte antibodies. The binding of C1q, C4 and C3 to the same cells was also inhibited by IVIG. Taken together these findings suggest that IVIG prevents the development of myositis in EAM and adoptive EAM models by several mechanisms, such as reducing anti-myosin antibody and by blocking complement activation. Our present findings might account for the clinical efficacy of IVIG in PM and DM patients.

Adoptive Transfer↗
PubMed2001

Role of beta isoform-specific insertions of Ca2+/calmodulin-dependent protein kinase II.

Alpha and beta isoforms of Ca2+/calmodulin-dependent protein kinase II (alpha and beta CaM kinase II, respectively) are highly conserved except for beta-specific insertions 1 and 2, located at amino acids 316-340 and 354-392, respectively. To investigate the role of these beta-specific insertions, we prepared the deletion mutants betaDelta1, betaDelta2 and betaDelta1/2, which lacked insertions 1, 2 and both, respectively. These mutant DNAs were expressed in neuroblastoma cells and compared with the wild-type enzyme. Green fluorescent protein tagged CaM kinase II was used to further explore the distribution of the kinase in living cells. Most (80%) of wild-type beta and mutant betaDelta1 were located in the particulate fraction, and distributed in the cell body and neurites, forming punctate or spot-like structures in the neurites. Mutants betaDelta2 and betaDelta1/2 were distributed in almost equal amounts in the soluble and particulate fractions. They were concentrated in the base of neurites and only partlially distributed throughout neurites, indicating that their transport to neurites was impaired. Beta(1-410), a deletion mutant of the association domain with a monomeric form, was located primarily in the soluble fraction. These results indicate that insertion 2, the association domain, and the oligomeric form of beta CaM kinase II play an important role in the cellular distribution of beta CaM kinase II.

Animals↗