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Biomedical subjects

Y Morikawa

Publications and source records attributed to Y Morikawa.

At least 19 recordsLinked to original sources

Complete overlap of interleukin-31 receptor A and oncostatin M receptor beta in the adult dorsal root ganglia with distinct developmental expression patterns.

Interleukin-31 receptor A (IL-31RA) is a newly identified type I cytokine receptor, that is related to gp130, the common receptor of the interleukin (IL) -6 family cytokines. Recent studies have shown that IL-31RA forms a functional receptor complex for IL-31 together with the beta subunit of oncostatin M receptor (OSMRbeta). However, little is known about the target cells of IL-31 because it remains unclear which types of cells express IL-31RA. In our previous reports, we demonstrated that OSMRbeta is expressed in a subset of small-sized nociceptive neurons of adult dorsal root ganglia (DRGs). In the present study, we investigated the IL-31RA expression in the adult and developing DRGs. From a northern blot analysis and in situ hybridization histochemistry, IL-31RA mRNA was found to be expressed in the adult DRGs. According to reverse-transcriptase polymerase chain reaction, IL-31RA mRNA was detected in the DRGs and trigeminal ganglia, while no expression of IL-31RA mRNA was observed in the CNS. Double immunofluorescence staining revealed IL-31RA to be expressed in a subset of small-sized neurons, all of which colocalized with OSMRbeta. In addition, the expression of IL-31 RA was detected in afferent fibers in the spinal cord and the dermis of the skin. We also found that the developmental expression pattern of IL-31RA was different from that of OSMRbeta; IL31RA-positive neurons in DRGs first appeared at postnatal day (PN) 10 and reached the adult level at PN14, whereas OSMRbeta-positive neurons were observed at PN0 for the first time. We previously demonstrated OSMRbeta-expressing neurons to decrease, however, they were not found to disappear in oncostatin M (OSM) -deficient mice. These findings suggest that IL-31 and OSM may thus have redundant functions in the development of OSMRbeta-expressing neurons.

Aging↗

Causes of death and renal tubular dysfunction in residents exposed to cadmium in the environment.

OBJECTIVES: To clarify the causes of death of residents with renal tubular dysfunction induced by cadmium (Cd) in the environment. METHODS: A 15 year follow up study was performed with the inhabitants living in the Cd polluted Kakehashi River basin in Japan. Standardised mortality ratios (SMRs) for causes of death, classified by ICD-9, were computed using the person-years method to investigate the excess mortality of subjects with urinary beta2-MG (microglobulin) > or =1000 microg/gCr. Mortality risk analysis was performed using Cox's proportional model to compare mortality between subjects with urinary beta2-MG > or =1000 and <1000 microg/gCr, and to investigate the relationship between the degree of urinary beta2-MG and mortality. RESULTS: Excess mortality due to heart failure and cerebral infarction in both sexes, and nephritis and nephrosis in men, was observed among subjects with urinary beta2-MG > or =1000 microg/gCr. Significant increases in mortality risk for cerebral infarction in men and for malignant neoplasms in women with urinary beta2-MG > or =1000 microg/gCr were observed during the first five year observation period. For nephritis and nephrosis, the mortality risks for men and women with urinary beta2-MG > or =1000 microg/gCr significantly increased over the 15 year observation period. The mortality risks for heart failure and cerebral infarction increased in proportion to the increased urinary beta2-MG in both sexes. Increased mortality risks for nephritis and nephrosis were identified in the subjects with urinary beta2-MG > or =10000 microg/gCr in both sexes. CONCLUSION: Renal tubular dysfunction induced by Cd affected the causes of death, and mortality for heart failure, cerebral infarction, and nephritis and nephrosis was increased among inhabitants living in a Cd polluted area in Japan. In women, cancer mortality may have been increased while Cd pollution was ongoing.

Aged↗

Induction of brain-derived neurotrophic factor by leptin in the ventromedial hypothalamus.

Leptin, an adipocyte-derived hormone, reduces food intake by regulating orexigenic and anorexigenic factors in the hypothalamus. Although brain-derived neurotrophic factor is an important anorexigenic factor in the hypothalamus, little is known about the regulation of brain-derived neurotrophic factor expression by leptin in the hypothalamus. In the present study, we examined the effect of leptin on the expression of brain-derived neurotrophic factor in the hypothalamus. I.V. administration of leptin (10 microg/g) led to the increase in the expression of brain-derived neurotrophic factor mRNA, which was observed in the dorsomedial part of the ventromedial hypothalamic nucleus. The increased expression of brain-derived neurotrophic factor mRNA was detected in phosphorylated signal transducer and activator of transcription 3-positive neurons, suggesting that leptin induced brain-derived neurotrophic factor expression in neurons of the dorsomedial part of the ventromedial hypothalamic nucleus. In addition, the expression of brain-derived neurotrophic factor was increased at the protein level in the ventromedial hypothalamic nucleus of leptin-injected mice. Interestingly, brain-derived neurotrophic factor-positive fibers also increased in the ventromedial hypothalamic nucleus and dorsomedial hypothalamic nucleus of leptin-injected mice, which were in close apposition to tyrosine kinase receptor B-immunoreactive neurons and colocalized with synaptophysin, a marker of presynaptic terminals. These results suggest that leptin induces brain-derived neurotrophic factor expression in the dorsomedial part of the ventromedial hypothalamic nucleus and brain-derived neurotrophic factor may exert as anorexigenic factors possibly through the activation of tyrosine kinase receptor B in the ventromedial hypothalamic nucleus and dorsomedial hypothalamic nucleus.

Animals↗

Cloning, functional expression and promoter analysis of xylanase III gene from Trichoderma reesei.

In this study, the xyn3 gene from the filamentous mesophilic fungus Trichoderma reesei (Hypocrea jecorina) PC-3-7 was cloned and sequenced. Analysis of the deduced amino acid sequence of XYN III revealed considerable homology with xylanases belonging to glycoside hydrolase family 10. These results show that XYN III is distinguishable from XYN I and XYN II, two other T. reesei xylanases that belong to the glycosidase family 11. When xyn3 was expressed in Escherichia coli, significant activity was observed in the cell-free extract, and higher activity (13.2 U/ml medium) was recovered from the inclusion bodies in the cell debris. The sequence of the 5'-upstream region of the gene in the parent strain QM9414 is identical to that of PC-3-7, although the expression level of xyn3 in PC-3-7 has been reported to be at least 1,000 times greater than in QM9414. These results suggest that xyn3 expression in T. reesei QM9414 is silenced. The consensus sequences for ACEI, ACEII, CREI, and the Hap2/3/5 protein complex are all present in the upstream region of xyn3. Deletion analysis of the upstream region revealed that two regions containing consensus sequences for the known regulatory elements play important roles for xyn3 expression.

Amino Acid Sequence↗

G-protein beta3 subunit variant C825T is a risk factor for hypertension in Japanese females--a prospective cohort study over 5 years.

The relationship between the G-protein beta3 subunit variant C825T and risk of hypertension was examined in a prospective cohort study of Japanese workers. This study included observations over a 5-year period from 1997 to 2002 on 878 males and 692 females who were normotensive at entry. Hypertension was defined as systolic blood pressure > or =140 mmHg and/or diastolic blood pressure > or =90 mmHg, or taking antihypertensive medication. Pooled logistic regression analyses were performed using C825T genotype, age, body mass index, lifestyle, and the result of blood chemistries as the covariates. Multivariate pooled logistic regression analysis showed the risk of hypertension was 2.31 times higher in females with the TT genotype than in females with the CC genotype (95% confidence interval: 1.07-4.96), after adjustment for the effects of other potential covariates. In contrast, no significant risk of hypertension was observed with the TT genotype in male subjects. This study indicates that the 825T allele is an independent risk factor for hypertension in Japanese females, and suggests that this polymorphism may be a beneficial prognostic marker for hypertension in the general Japanese female population.

Adult↗

Hydrogen-induced instability of the Ge(105) surface.

The structure and stability of the hydrogen-terminated (105) surface of Ge deposited on Si(105) substrates are investigated by scanning tunneling microscopy (STM). Investigations combining STM, electron energy loss spectroscopy, and theory reveal that Si incorporation into the surface Ge layer of hydrogen-terminated Ge/Si(105) drastically destabilizes the surface. The STM images obtained on this surface are well explained by the recently established rebonded-step structure model.

Journal Article↗

TRPV2, a capsaicin receptor homologue, is expressed predominantly in the neurotrophin-3-dependent subpopulation of primary sensory neurons.

TRPV2, a member of transient receptor potential ion channels, responds to high-threshold noxious heat, but neither to capsaicin nor to proton. Although TRPV2 is expressed in medium- to large-sized dorsal root ganglion (DRG) neurons with myelinated fibers in adult rodents, little is known about the neurotrophin dependence of TRPV2-positive neurons in the developing and adult DRGs of mice. In the present study, using immunohistochemistry, we found that TRPV2 was first expressed in DRG neurons at embryonic day (E) 11.5, when neither TRPV1 nor TRPM8 was detected yet. Double-immunofluorescence staining revealed that tyrosine kinase receptor C (TrkC) was expressed in most of TRPV2-positive DRG neurons at E11.5 and E13.5. In addition, the percentage of TRPV2-positive neurons in the total DRG neurons at E13.5 reached the same as that of adulthood. In adult DRGs, TrkC and Ret were expressed in 68% and 25% of TRPV2-positive neurons, respectively. These results suggest that TRPV2 is expressed predominantly in the NT-3-dependent subpopulation of DRG neurons throughout development and in adult mice.

Age Factors↗

Up-regulated phosphorylation of signal transducer and activator of transcription 3 and cyclic AMP-responsive element binding protein by peripheral inflammation in primary afferent neurons possibly through oncostatin M receptor.

Oncostatin M (OSM), a member of interleukin-6 family cytokines, contributes to the development of nociceptive sensory neurons. However, little is known about the role of OSM in dorsal root ganglia (DRGs) of adult mice after peripheral inflammation. In the present study, we showed that OSM mRNA was highly expressed in the inflamed skin during acute inflammation induced by complete Freund's adjuvant (CFA), while the expression of oncostatin M receptor (OSMR) did not change in the ipsilateral DRG. Although peripheral inflammation induced significant increases in the number of neurons with phosphorylated extracellular signal-regulated kinase (p-ERK) and phosphorylated p38 mitogen-activated protein kinase (p-p38) in ipsilateral DRGs, OSMR-positive neurons exhibited neither p-ERK nor p-p38. In addition, we found significant increases in the number of neurons with phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and phosphorylated cAMP-responsive element binding protein (p-CREB) in the ipsilateral DRGs. Interestingly, OSMR-positive neurons with p-STAT3 and p-CREB were significantly increased after peripheral inflammation. Thus, our results suggest that acute inflammation induce the phosphorylations of several signal molecules, including ERK, p38, cAMP-responsive element binding protein, and STAT3. Among them, the up-regulation of p-STAT3 and p-CREB may be induced possibly through OSMR.

Animals↗

Expression of mKirre, a mammalian homolog of Drosophila kirre, in the developing and adult mouse brain.

mKirre, a mammalian homolog of the Drosophila kirre, is expressed in bone marrow stromal cells and the brain. Although mKirre has been shown to support the hematopoietic stem cells, little is known about the function of mKirre in the brain. In the present study, to gain insights into the function of mKirre, we investigated the expression pattern of mKirre gene in the developing and adult mouse brain using in situ hybridization. In the adult brain, mKirre mRNA was highly expressed in the olfactory bulb, the piriform cortex, the cochlear nucleus, and the cerebellum. At embryonic day (E) 11.5, we could observe mKirre mRNA in the differentiating zones of various regions, such as the caudate-putamen, the geniculate body, the thalamus, the amygdala, and the brainstem. Its gene expression in these regions at E11.5 also persisted to the adult, in which its expression levels were much less prominent. After birth, we could first observe high expression of mKirre mRNA in the glomerular and mitral layers of the olfactory bulb, the cortical plate of the neocortex, the cochlear nucleus, and the molecular and granule cell layers of the cerebellum. In the hippocampus, its gene expression was first observed in the dentate gyrus at postnatal day 7. The spatiotemporal expression pattern of mKirre mRNA suggests important roles of mKirre in later developmental processes, especially the synapse formation.

Age Factors↗

Imaging of all dangling bonds and their potential on the Ge/Si105 surface by noncontact atomic force microscopy.

High-resolution noncontact atomic force microscope (AFM) images were successfully taken on the Ge105-(1 x 2) structure formed on the Si105 substrate and revealed all dangling bonds of the surface regardless of their electronic situation, surpassing scanning tunneling microscopy, whose images strongly deviated from the atomic structure by the electronic states involved. An atomically resolved electrostatic potential profile by a Kelvin-probe method with AFM shows potential variations among the dangling bond states, directly observing a charge transfer between them. These results clearly demonstrate that high-resolution noncontact AFM with a Kelvin-probe method is an ideal tool for analysis of atomic structures and electronic properties of surfaces.

Journal Article↗

Foxp1 gene expression in projection neurons of the mouse striatum.

The developmental processes of maturation in the CNS are the result of specific events including mitogenesis, differentiation, and cell death which occur in a precise spatial and temporal manner. It has been reported that many transcription factors, including forkhead transcription factors, play a key role in these processes. First, we examined the expression pattern of the forkhead transcription factor Foxp1 in the adult CNS. Foxp1 was highly expressed in the striatum and moderately in the cerebral cortex, CA1/2 subfields of the hippocampus, and several thalamic nuclei. In situ hybridization combined with immunohistochemistry in the striatum of adult mice revealed that Foxp1 mRNA was detected in a subset of projection neurons, not in interneurons. In addition, the expression of Foxp1 mRNA was observed in the developing basal ganglia with the exception of the globus pallidus. Thus, Foxp1 mRNA was expressed in a subset of striatal projection neurons, probably the matrix neurons. The expression pattern of Foxp1 mRNA suggests that Foxp1 may play a role in the development and formation of a circuit in the basal ganglia, which is involving the matrix neurons.

Animals↗

Exercise blood pressure in young adults as a predictor of future blood pressure: a 12-year follow-up of medical school graduates.

It has not been fully clarified whether exercise blood pressure (BP) in young adult men and women is useful to predict future BP, especially in Asian people. A long-term prospective study was conducted in graduates of a medical school in Japan; 138 men and 76 women whose mean age was 19.8 and 19.2, respectively, at baseline. A 5-min exercise tolerance test was performed at baseline, and BP immediately after exercise was measured. BP at 50% intensity exercise was also calculated. Multiple regression analysis was carried out to clarify the relationship of exercise BP at baseline to follow-up BP after an average of 12 years. In multivariate-adjusted models, the relationship of systolic blood pressure (SBP) at follow-up was stronger to SBP immediately after exercise (F=7.7, P=0.006) than to resting SBP (F=3.7, P=0.055) in men. The models in men showed that SBP immediately after exercise was a stronger predictor of follow-up SBP than SBP at 50% intensity exercise, and the results were similar for diastolic blood pressure (DBP) in men. For SBP in women, resting SBP was the strongest predictor of follow-up SBP (F=14.3, P<0.001), and exercise SBP was not significant predictor. For DBP in women, any DBP at rest or after exercise was not significantly related to DBP at follow-up. In young adult men, SBP and DBP immediately after exercise would be a stronger predictor of future SBP and DBP rather than BP at rest. However, in young adult women, resting SBP rather than exercise SBP would be better to predict future SBP.

Adult↗

Fasting-induced activation of mitogen-activated protein kinases (ERK/p38) in the mouse hypothalamus.

Activity-dependent changes in neuronal plasticity depend critically on gene regulation. To understand how fasting-induced stimulation leads to gene regulation through intracellular signalling pathways, we investigated the effect of fasting on activation of the mitogen-activated protein kinase (MAPK) family, the extracellular signal-regulated kinase (ERK) and the p38 MAPK (p38) in mouse hypothalamus. In the hypothalamic arcuate nucleus, phosphorylation of ERK significantly increased during fasting, spatially coincident with phosphorylation of cAMP response element binding protein (CREB), induction of c-Fos, and expression of neuropeptide Y (NPY). In the paraventricular nucleus (PVN) of fasted mice, activation of p38 in addition to ERK was also observed. In the arcuate nucleus of ob/ob mice, phosphorylations of ERK and CREB were decreased during fasting, whereas the expression of NPY was increased. In the PVN, increased activation of p38 was observed in spite of decreased activation of ERK. These results suggest that ERK and p38 are differentially activated by fasting in distinct regions of the hypothalamus depending on the condition of energy balance.

Animals↗

Localization of oncostatin M receptor beta in adult and developing CNS.

Oncostatin M (OSM) is a member of the interleukin-6 cytokine family, which is involved in definitive hematopoiesis, the development of liver, and local inflammation. However, little is known about the role of OSM in the murine CNS. Using Northern blot analysis, we examined the regional distribution of OSM receptor beta (OSMRbeta) mRNA in the adult CNS. OSMRbeta mRNA was observed predominantly in the olfactory bulb, and with low levels in the other regions. In situ hybridization shows that OSMRbeta gene expression was found in astrocytes of olfactory bulb, epithelial cells of choroid plexus, and meningeal cells in pia mater. In addition, we investigated the gene expression of OSMRbeta in the developing CNS at different time points. Its gene expression was first observed in large neurons of the hypoglossal nucleus at 14.5 days postcoitum, which was sustained until neonatal mice. OSMRbeta mRNA and protein were mainly localized in the ventral subnucleus of the developing hypoglossal nucleus. Our results suggest that OSM contributes to the development of specific subpopulations of both neurons and astrocytes in the murine CNS.

Animals↗

Identification of human SEP1 as a glial cell line-derived neurotrophic factor-inducible protein and its expression in the nervous system.

Glial cell line-derived neurotrophic factor (GDNF) signals through multisubunit receptor complex consisting of RET tyrosine kinase and a glycosylphosphatidylinositol-anchored coreceptor called GDNF family receptor alpha1 (GFRalpha1). In the current study, we cloned a human SEP1 gene as a GDNF-inducible gene using human neuroblastoma cells that express RET and GFRalpha1. The induction of the SEP1 gene showed two peaks at 0.5-2 h and 24-48 h after GDNF stimulation by Northern blotting and quantitative real-time reverse transcriptase polymerase chain reaction. The late induction was also confirmed at protein levels by Western blotting with anti-SEP1 antibody. Immunostaining revealed that the expression of the SEP1 protein was detected in cell body, elongated neurites and growth cone-like structure of neuroblastoma cells treated with GDNF. In addition, we found a high level of SEP1 expression in neurons of the dorsal root and superior cervical ganglia and motor neurons of the spinal cord of mice in which RET is also expressed. SEP1 was co-immunoprecipitated with alpha- and beta-tubulins from the lysate of mouse brain. These results thus suggested that SEP1 is a GDNF-inducible and microtubule-associated protein that may play a role in the nervous system.

Animals↗

Origin of the stability of Ge(105) on si: a new structure model and surface strain relaxation.

The structure of Ge(105)-(1 x 2) grown on Si(105) is examined by scanning tunneling microscopy (STM) and first-principles calculations. The morphology evolution with an increasing amount of Ge deposited documents the existence of a tensile surface strain in Si(105) and its relaxation with increasing coverage of Ge. A detailed analysis of high-resolution STM images and first-principles calculations produce a new stable model for the Ge(105)-(1 x 2) structure formed on the Si(105) surface that includes the existence of surface strain. It corrects the model developed from early observations of the facets of "hut" clusters grown on Si(001).

Journal Article↗

A cross-sectional study on association of calcium intake with blood pressure in Japanese population.

To investigate the association of calcium intake independently of other nutrients already known as predictors of hypertension, a cross-sectional study was carried out on the same population in Japan as used for the INTERSALT study. Dietary calcium intake was estimated from a 1-day 24-h recall. Sodium and potassium intakes were evaluated by 24-h urinary excretion. Data from 476 subjects aged 20-59 years, 230 men and 246 women, were analysed. The mean dietary calcium intake ranged from 557 to 608 mg/day among men, and from 528 to 639 mg/day among women. Among men, the pooled estimate of the regression coefficients of blood pressure (mm Hg) per 100 mg increase of calcium intake, adjusted for age and body mass index (BMI), were -0.42 mm Hg for systolic blood pressure (SBP) and -0.35 mm Hg for diastolic blood pressure (DBP), but there was no statistical significance. Among women, the pooled estimates of regression coefficients adjusted for age and BMI were -0.92 mm Hg for SBP and -0.83 mm Hg for DBP with statistical significance. After adjustment for age, BMI, alcohol intake and urinary excretion of sodium and potassium, the pooled estimate of calcium intake was -0.66 mm Hg for DBP with statistical significance and -0.70 mm Hg for SBP. A significant negative association of calcium intake with blood pressure was observed among the subjects in Osaka. Our study suggests that increased calcium intake may provide a benefit of lowering blood pressure independently of other minerals such as sodium and potassium.

Adult↗

Epidemiology of idiopathic cardiomyopathy in Japan: results from a nationwide survey.

OBJECTIVE: To estimate the total number of patients with idiopathic cardiomyopathy in Japan and the prevalence of the disorder. DESIGN: A nationwide epidemiological survey. SETTING: Hospitals selected randomly from among all hospitals in Japan. PATIENTS: Patients presenting with any of the three types of idiopathic cardiomyopathy: dilated cardiomyopathy, hypertrophic cardiomyopathy, and restrictive cardiomyopathy. MAIN OUTCOME MEASURES: The total number of patients in Japan was estimated using the sampling and response rates in each stratum with respect to hospital size. The second survey was conducted for patients reported in the first survey in order to obtain detailed information, including age, sex, and specific clinical data. RESULTS: Estimated patient totals and 95% confidence intervals (CI) were 17 700 (95% CI 16 500 to 18 800) for dilated cardiomyopathy, 21 900 (95% CI 20 600 to 23 200) for hypertrophic cardiomyopathy, and 300 (95% CI 250 to 350) for restrictive cardiomyopathy. Crude prevalence per 100 000 population was estimated as 14.0 for dilated cardiomyopathy, 17.3 for hypertrophic cardiomyopathy, and 0.2 for restrictive cardiomyopathy; crude incidence per 100 000 person-years was estimated as 3.58, 4.14, and 0.06, respectively. CONCLUSIONS: The total number and prevalence of patients with idiopathic cardiomyopathy in Japan are estimated for the first time in a nationwide survey. The prevalence of dilated cardiomyopathy in Japan appears to be about half that of Western populations, while that of hypertrophic cardiomyopathy is about the same.

Adolescent↗