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Rie Miyata,
Naoyuki Tanuma,
Masaharu Hayashi, Takuji Imamura,
Jun-ichi Takanashi,
Rieko Nagata,
Akihisa Okumura,
Hirohumi Kashii,
Sunao Tomita,
Satoko Kumada,
Masaya Kubota
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ABSTRACT: We examined oxidative stress markers, tau protein and cytokines in the cerebrospinal fluid (CSF) in six patients with clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS). In the CSF, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and hexanoyl-lysine adduct levels increased over the cutoff index in four and one out of six MERS patients, respectively. The CSF IL-6 and IL-10 levels were increased in three out of six patients, two of which had extended lesion of the cerebral white matter. The CSF value of tau protein, marker of the axonal damage, was not increased, and neuron specific enolase (NSE) in the CSF was not increased. The increased 8-OHdG levels in the CSF, DNA oxidative stress marker, in four MERS patients, suggesting involvement of oxidative stress in MERS. MERS is occasionally accompanied with hyponatremia, although our patients lacked hyponatremia. It is possible that the disequilibrium of systemic metabolism including electrolytes may lead to facilitation of oxidative stress and reversible white matter lesion in MERS. The increase of cytokine production seems to be involved in the distribution of lesions in MERS.
Brain & development 05/2011; 34(2):124-7. · 1.74 Impact Factor
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ABSTRACT: We first report sisters presenting with clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS)-like features, i.e., mild and reversible neurological manifestations, and MRI finding of a reversible lesion with transiently reduced diffusion in the corpus callosum associated with symmetrical white matter. The distributions of the white matter lesions (more extensive) and Na levels (normal) were different from those reported for sporadic MERS patients (subcortical white matter close to the central sulci, and hyponatremia), which suggested that the pathophysiology of the sisters with MERS-like features might be different from that of sporadic MERS. Some genetic factors might be involved in MERS, especially in some patients with extensive white matter lesions.
Journal of the neurological sciences 03/2010; 290(1-2):153-6. · 2.32 Impact Factor
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ABSTRACT: The observations that atherosclerosis often occurs in non-smokers without elevated levels of low-density lipoprotein cholesterol, and that most atherosclerosis loci so far identified in mice do not affect systemic risk factors associated with atherosclerosis, suggest that as-yet-unidentified mechanisms must contribute to vascular disease. Arterial walls undergo regional disturbances of metabolism that include the uncoupling of respiration and oxidative phosphorylation, a process that occurs to some extent in all cells and may be characteristic of blood vessels being predisposed to the development of atherosclerosis. To test the hypothesis that inefficient metabolism in blood vessels promotes vascular disease, we generated mice with doxycycline-inducible expression of uncoupling protein-1 (UCP1) in the artery wall. Here we show that UCP1 expression in aortic smooth muscle cells causes hypertension and increases dietary atherosclerosis without affecting cholesterol levels. UCP1 expression also increases superoxide production and decreases the availability of nitric oxide, evidence of oxidative stress. These results provide proof of principle that inefficient metabolism in blood vessels can cause vascular disease.
Nature 06/2005; 435(7041):502-6. · 36.28 Impact Factor
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ABSTRACT: The observations that atherosclerosis often occurs in non-smokers without elevated levels of low-density lipoprotein cholesterol, and that most atherosclerosis loci so far identified in mice do not affect systemic risk factors associated with atherosclerosis
Nature 05/2005; 435(7041):502-506. · 36.28 Impact Factor
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ABSTRACT: Pancreatitis is a common disease with substantial morbidity and mortality. To better understand the mechanisms conferring sensitivity or resistance to pancreatitis, we have initiated the analysis of novel acinar cell proteins. Integral membrane-associated protein-1 (Itmap1) is a CUB (complement subcomponents C1r/C1s, sea urchin Uegf protein, bone morphogenetic protein-1) and zona pellucida (ZP) domain-containing protein we find prominently expressed in pancreatic acinar cells. Within the acinar cell, Itmap1 localizes to zymogen granule membranes. Although roles in epithelial polarity, granule assembly, and mucosal protection have been postulated for CUB/ZP proteins, in vivo functions for these molecules have not been proven. To determine the function of Itmap1, we generated Itmap1-deficient mice. Itmap1(-/-) mice demonstrate increased severity of secretagogue- and diet-induced pancreatitis in comparison to Itmap1(+/+) mice. In contrast to previous animal models exhibiting altered severity of pancreatitis, Itmap1 deficiency results in impaired activation of trypsin, an enzyme believed critical for initiating a cascade of digestive zymogen activation during pancreatitis. Itmap1 deficiency does not alter zymogen granule size, appearance, or the composition of zymogen granule contents. Our results demonstrate that Itmap1 plays an essential role in trypsinogen activation and that both impaired and augmented trypsinogen activation can be associated with increased severity of pancreatitis.
Journal of Biological Chemistry 01/2003; 277(52):50725-33. · 4.77 Impact Factor
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ABSTRACT: Prostaglandins are essential for the initiation of parturition in mice. The peak in uterine prostaglandin F(2)(alpha) levels occurs at d 19.0 of gestation, just before the onset of labor. Our studies set out to determine the important regulatory step(s) involved in this increase of prostaglandin F(2)(alpha). We show that cytosolic phospholipase A(2) mRNA, protein, and activity do not significantly vary during mouse gestation. Rather, our studies demonstrate that cyclooxygenase-1 mRNA is abruptly induced at d 15.5 of gestation, but cyclooxygenase-1 protein levels only gradually increase throughout gestation. In contrast, cyclooxygenase-2 protein remains constant during gestation. We find that prostaglandin F synthase protein increases significantly during gestation reaching peak levels between d 15.5 and d 17.5 of gestation. We also find that the level of prostaglandin dehydrogenase, responsible for degradation of prostaglandins, decreases during late gestation. Taken together these results suggest that the regulation of prostaglandin F(2)(alpha) is a complex process involving the coordinate induction of synthetic enzymes along with a decrease in degradative enzymes involved in prostaglandin metabolism.
Endocrinology 08/2002; 143(7):2593-8. · 4.46 Impact Factor
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ABSTRACT: Prostaglandins (PGs) have been recently proven essential for parturition in mice. To dissect the contributions of the two
cyclooxygenase (COX) isoforms to the synthesis of PGs during pregnancy, we have characterized the parturition phenotype of
COX-1-deficient mice. We find that mice with targeted disruption of the COX-1 gene have delayed parturition resulting in neonatal
death. Results of matings of COX-1-deficient females with COX-1 intact males, and blastocyst transfer of COX-1-deficient or
-intact embryos into wild-type foster mothers, proved necessity and sufficiency of maternal COX-1 for the normal onset of
labor. COX-1 expression is induced in gravid murine uterus and by in situ hybridization; this induction is localized to the decidua. Measurement of uterine PGs further confirmed that COX-1 accounted
for the majority of PGF2α production. To evaluate the interaction of PGs with oxytocin during murine labor, we generated mice
deficient in both oxytocin and COX-1. Surprisingly, the combined oxytocin and COX-1-deficient mice initiated labor at the
normal time. COX-1-deficient mice demonstrated impaired luteolysis, as evidenced by elevated serum progesterone concentration
and ovarian histology late in gestation, and delayed induction of uterine oxytocin receptors. In contrast, simultaneous oxytocin
and COX-1 deficiency restored the normal onset of labor by allowing luteolysis in the absence of elevated PGF2α production.
These findings demonstrate that COX-1 is essential for normal labor in the mouse, with a critical function being to overcome
the luteotrophic action of oxytocin in late gestation.
Proceedings of the National Academy of Sciences 09/1998; 95(20):11875-11879. · 9.68 Impact Factor
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Yoshiyuki Okano,
Minoru Asada,
Akie Fujimoto,
Akira Ohtake,
Koichiro Murayama,
Kwang-Jen Hsiao,
Kyuchul Choeh,
Yanling Yang,
Qixiang Cao,
Juergen K V Reichardt,
Shizuhiro Niihira, Takuji Imamura,
Tsunekazu Yamano
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ABSTRACT: Galactokinase (GALK) deficiency is an autosomal recessive disorder characterized by hypergalactosemia and cataract formation. Through mass screening of newborn infants, we identified a novel and prevalent GALK variant (designated here as the “Osaka” variant) associated with an A198V mutation in three infants with mild GALK deficiency. GALK activity and the amount of immunoreactive protein in the mutant were both 20% of normal construct in expression analysis. The Km values for galactose and ATP-Mg2+ in erythrocytes with homozygous A198V were similar to those of the healthy adult control subjects. A population study for A198V revealed prevalences of 4.1% in Japanese and 2.8% in Koreans, lower incidence in Taiwanese and Chinese, no incidence in blacks and whites from the United States, and a significantly high frequency (7.8%; P<.023) in Japanese individuals with bilateral cataract. This variant probably originated in Japanese and Korean ancestors and is one of the genetic factors that causes cataract in elderly individuals.
