Yoshiaki Tamura

Publications (44)156.36 Total impact

• Article: Overview of Differential VLBI Observations of Lunar Orbiters in SELENE (Kaguya) for Precise Orbit Determination and Lunar Gravity Field Study

  Hideo Hanada, Takahiro Iwata, Qinghui Liu, Fuyuhiko Kikuchi, Koji Matsumoto, Sander Goossens, Yuji Harada, Kazuyoshi Asari, Toshiaki Ishikawa, Yoshiaki Ishihara, [......], Wataru Masui, Koji Tanaka, Hironori Maejima, Xiaoyu Hong, Jinsong Ping, Xian Shi, Qian Huang, Yusufu Aili, Simon Ellingsen, Wolfgang Schlüter
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  ABSTRACT: The Japanese lunar explorer SELENE (Kaguya), which was launched on September 14th, 2007, was the target of VLBI observations over the period November 2007 to June 2009. These observations were made in order to improve the lunar gravity field model, in particular the lower degree coefficients and the model near the limb. Differential VLBI Radio sources, called VRAD instruments, were on-board the subsatellites, Rstar (Okina) and Vstar (Ouna), and the radio signals were observed by the Japanese VERA (VLBI Exploration of Radio Astrometry) network, and an international VLBI network. Multi-frequency and same-beam VLBI techniques were utilized and were essential aspects of the successful observing program. Multi-frequency VLBI was employed in order to improve the accuracy of the orbit determination obtained from the phase delay from the narrow-band satellite signals, while the same-beam VLBI method was used to resolve the cycle ambiguity which is inherent in the multi-frequency VLBI method. The observations were made at three S-band frequencies (2212, 2218 and 2287 MHz), and one X-band frequency (8456 MHz). We have succeeded in correlating the recorded signals from Okina/Ouna, and we obtained phase delays with an accuracy of several pico-seconds at S-band. KeywordsLunar explorer-VLBI-Gravity field-Orbit determination
  Space Science Reviews 04/2012; 154(1):123-144. · 3.61 Impact Factor
• Source

  Available from: Marina Yamada

  Article: NO donor induces Nec-1-inhibitable, but RIP1-independent, necrotic cell death in pancreatic β-cells.

  Yoshiaki Tamura, Yuko Chiba, Toshihiro Tanioka, Nobuyuki Shimizu, Shohei Shinozaki, Marina Yamada, Kentaro Kaneki, Seijiro Mori, Atsushi Araki, Hideki Ito, Masao Kaneki
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  ABSTRACT: Nitric oxide (NO) has been implicated in pancreatic β-cell death in the development of diabetes. The mechanisms underlying NO-induced β-cell death have not been clearly defined. Recently, receptor-interacting protein-1 (RIP1)-dependent necrosis, which is inhibited by necrostatin-1, an inhibitor of RIP1, has emerged as a form of regulated necrosis. Here, we show that NO donor-induced β-cell death was inhibited by necrostatin-1. Unexpectedly, however, RIP1 knockdown neither inhibited cell death nor altered the protective effects of necrostatin-1 in NO donor-treated β-cells. These results indicate that NO donor induces necrostatin-1-inhibitable necrotic β-cell death independent of RIP1. Our findings raise the possibility that NO-mediated β-cell necrosis may be a novel form of signal-regulated necrosis, which play a role in the progression of diabetes.
  FEBS letters 08/2011; 585(19):3058-64. · 3.54 Impact Factor
• Source

  Available from: Marina Yamada

  Article: Farnesyltransferase inhibitor FTI-277 reduces mortality of septic mice along with improved bacterial clearance.

  Wen Yang, Marina Yamada, Yoshiaki Tamura, Kyungho Chang, Ji Mao, Lin Zou, Yan Feng, Kotaro Kida, Marielle Scherrer-Crosbie, Wei Chao, Fumito Ichinose, Yong-Ming Yu, Alan J Fischman, Ronald G Tompkins, Shanglong Yao, Masao Kaneki
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  ABSTRACT: Treatment with statins, inhibitors of HMG-CoA reductase, extends the survival of septic mice. However, the molecular mechanisms underlying the cholesterol-lowering, independent beneficial effects of statins in sepsis are poorly understood. The inhibition of protein isoprenylation, namely farnesylation and geranylgeranylation, has been proposed as a mediator of the pleiotropic protective effects of statins, although direct evidence is lacking. Major features of sepsis-induced immune suppression include T-cell dysfunction, which is characterized by apoptosis of splenic T cells, increased CD4(+)Foxp3(+) regulatory T cells (Tregs), and suppression of type 1 helper T-cell response [e.g., interferon-γ (IFN-γ) secretion] in mice. Here, we show that the induction of sepsis by cecal ligation and puncture (CLP) resulted in increases in farnesyltransferase activity and farnesylated proteins in the spleen relative to sham operation. Treatment with farnesyltransferase inhibitor N-[4-[2(R)-amino-3-mercaptopropyl]amino-2-phenylbenzoyl]methionine methyl ester trifluoroacetate salt (FTI-277) (25 mg/kg b.wt. i.p.) at 2 h after CLP blocked the increase in farnesylated proteins and improved survival and bacterial clearance of septic mice. FTI-277 reverted to or mitigated sepsis-induced apoptosis in spleen and thymus, increased splenic CD4(+)Foxp3(+) Tregs, and suppressed IFN-γ secretion and proliferation of splenocytes in response to anti-CD3+CD28 antibodies in mice. Moreover, FTI-277 promoted macrophage phagocytotic activity in septic mice. These results indicate that elevation in protein farnesylation plays a role in derangements in immune function and mortality of septic mice. These findings suggest that prevention of immune dysfunction might contribute to FTI-277-induced improvement in survival of septic mice. These data highlight protein farnesyltransferase as a novel potential molecular target to reduce the mortality of patients with sepsis.
  Journal of Pharmacology and Experimental Therapeutics 08/2011; 339(3):832-41. · 3.83 Impact Factor
• Article: Inducible nitric-oxide synthase and nitric oxide donor decrease insulin receptor substrate-2 protein expression by promoting proteasome-dependent degradation in pancreatic beta-cells: involvement of glycogen synthase kinase-3beta.

  Toshihiro Tanioka, Yoshiaki Tamura, Makiko Fukaya, Shohei Shinozaki, Ji Mao, Minhye Kim, Nobuyuki Shimizu, Tadahiro Kitamura, Masao Kaneki
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  ABSTRACT: Insulin receptor substrate-2 (IRS-2) plays a critical role in the survival and function of pancreatic β-cells. Gene disruption of IRS-2 results in failure of the β-cell compensatory mechanism and diabetes. Nonetheless, the regulation of IRS-2 protein expression in β-cells remains largely unknown. Inducible nitric-oxide synthase (iNOS), a major mediator of inflammation, has been implicated in β-cell damage in type 1 and type 2 diabetes. The effects of iNOS on IRS-2 expression have not yet been investigated in β-cells. Here, we show that iNOS and NO donor decreased IRS-2 protein expression in INS-1/832 insulinoma cells and mouse islets, whereas IRS-2 mRNA levels were not altered. Interleukin-1β (IL-1β), alone or in combination with interferon-γ (IFN-γ), reduced IRS-2 protein expression in an iNOS-dependent manner without altering IRS-2 mRNA levels. Proteasome inhibitors, MG132 and lactacystin, blocked the NO donor-induced reduction in IRS-2 protein expression. Treatment with NO donor led to activation of glycogen synthase kinase-3β (GSK-3β) and c-Jun N-terminal kinase (JNK/SAPK) in β-cells. Inhibition of GSK-3β by pharmacological inhibitors or siRNA-mediated knockdown significantly prevented NO donor-induced reduction in IRS-2 expression in β-cells. In contrast, a JNK inhibitor, SP600125, did not effectively block reduced IRS-2 expression in NO donor-treated β-cells. These data indicate that iNOS-derived NO reduces IRS-2 expression by promoting protein degradation, at least in part, through a GSK-3β-dependent mechanism. Our findings suggest that iNOS-mediated decreased IRS-2 expression may contribute to the progression and/or exacerbation of β-cell failure in diabetes.
  Journal of Biological Chemistry 06/2011; 286(33):29388-96. · 4.77 Impact Factor
• Article: Upregulation of circulating IL-15 by treadmill running in healthy individuals: is IL-15 an endocrine mediator of the beneficial effects of endurance exercise?

  Yoshiaki Tamura, Keiichi Watanabe, Tomomi Kantani, Junichi Hayashi, Nobuhiko Ishida, Masao Kaneki
  [show abstract] [hide abstract]
  ABSTRACT: The beneficial effects of endurance exercise include insulin-sensitization and reduction of fat mass. Limited knowledge is available about the mechanisms by which endurance exercise exerts the salutary effects. Myokines, cytokines secreted by skeletal muscle, have been recognized as a potential mediator. Recently, a role of skeletal muscle-derived interleukin-15 (IL-15) in improvement of fat-lean body mass composition and insulin sensitivity has been proposed. Yet, previous studies have reported that endurance training does not increase production or secretion of IL-15 in skeletal muscle. Here, we show that in opposition to previous findings, 30-min treadmill running at 70% of age-predicted maximum heart rate resulted in a significant increase in circulating IL-15 level in untrained healthy young men. These findings suggest that IL-15 might play a role in the systemic anti-obesogenic and insulin-sensitizing effects of endurance exercise, not only as a paracrine and autocrine but also as an endocrine factor.
  Endocrine Journal 02/2011; 58(3):211-5. · 2.03 Impact Factor
• Article: Cooperative effect of serum 25-hydroxyvitamin D concentration and a polymorphism of transforming growth factor-beta1 gene on the prevalence of vertebral fractures in postmenopausal osteoporosis.

  Seijiro Mori, Noriyuki Fuku, Yuko Chiba, Fumiaki Tokimura, Takayuki Hosoi, Yoshiyuki Kimbara, Yoshiaki Tamura, Atsushi Araki, Masashi Tanaka, Hideki Ito
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  ABSTRACT: A T869-->C polymorphism of the transforming growth factor-beta1 (TGF-beta1) gene is reported to be associated with genetic susceptibility to both osteoporosis and vertebral fractures. A low serum 25-hydroxyvitamin D [25(OH)D] level is known to be associated with a higher risk for hip fracture. This study aimed to assess a possible cooperative effect of the gene polymorphism and vitamin D status on vertebral fracture risk. The prevalence of vertebral fracture in 168 postmenopausal female patients with osteoporosis was analyzed, and its association with the TGF-beta1 gene polymorphism and serum 25(OH)D concentration was assessed cross-sectionally. The fracture prevalence increased according to the rank order of the TGF-beta1 genotypes CC < CT < TT, as expected. A significant difference was found not only between the CC and TT genotypes (P = 0.005) but also between the CC and CT genotypes (P < 0.05) when the patients with serum 25(OH)D of more than the median value [22 ng/ml (55 nmol/l)] were analyzed. On the other hand, when those with serum 25(OH)D of less than the median value were analyzed, the protective effect of the C allele against the fracture was blunted; statistical significance in the difference of the fracture prevalence was lost between the CC genotype and the other genotypes. These data suggest that vitamin D fulfillment is prerequisite for the TGF-beta1 genotype in exerting its full effect on the fracture prevalence.
  Journal of Bone and Mineral Metabolism 07/2010; 28(4):446-50. · 2.27 Impact Factor
• Article: [Community participation is associated with life satisfaction in elderly people with diabetes mellitus].

  Mitsuko Takahashi, Atsushi Araki, Shuichirou Watanabe, Hiroshi Haga, Yoshiyuki Kimbara, Yoshiaki Tamura, Yuko Chiba, Seijiro Mori, Hideki Ito, Hiroshi Shibata
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  ABSTRACT: Comprehensive questionnaires encompassing physical, psychological, and social aspects were administered by interview to 56 elderly outpatients with diabetes mellitus. Life satisfaction was assessed using the Life Satisfaction Index K (LSIK) . We also assessed the emotional and instrumental social support provided by the families living along with the participants or living separately from the participants. The Index of Social Interaction (18 items) was used to assess the social relationships and the environmental social resources, which were classified into 5 domains: 1) independence, 2) social curiosity, 3) relationships with other people, 4) participation in the community, and 5) feelings of safety. In a univariate analysis, the presence of diabetic neuropathy and pain in the lower back or knee joints were associated with low LSIK scores. Community participation, social curiosity, relationships with other people, and instrumental support from families living together with the participants positively correlated with high LSIK scores. The LSIK scores of the leaders of the diabetes patient group were higher than the scores of those who only participated in the diabetes patient group. In a multiple linear regression analysis, community participation, instrumental support from families living along with the participants, and the absence of neuropathy were independently associated with high LSIK scores. Community participation is an important factor associated with life satisfaction in elderly people with diabetes mellitus.
  Nippon Ronen Igakkai Zasshi Japanese Journal of Geriatrics 01/2010; 47(2):140-6.
• Article: Hypoglycemia due to ectopic secretion of insulin-like growth factor-I in a patient with an isolated sarcoidosis of the spleen.

  Yuiko Ogiwara, Seijiro Mori, Mizuki Iwama, Motoji Sawabe, Minoru Takemoto, Nobuo Kanazawa, Koh Furuta, Izumi Fukuda, Yoshitaka Kondo, Yoshiyuki Kimbara, Yoshiaki Tamura, Yuko Chiba, Atsushi Araki, Koutaro Yokote, Naoki Maruyama, Hideki Ito
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  ABSTRACT: Hypoglycemia is reported to be one of the manifestations of a patient with hypothalamic sarcoid infiltrates due to impaired counter-regulation of glucose. But, without hypothalamic lesion, patients with sarcoidosis would not be expected to have hypoglycemia. We recently identified a patient with an isolated sarcoidosis of the spleen who had experienced frequent fasting hypoglycemia which completely disappeared after splenectomy. During hypoglycemia, serum insulin was undetectable. Endocrinological examination revealed no abnormality. The objective was to investigate whether the patient's hypoglycemia was due to ectopic secretion of an insulin-mimetic factor by the splenic sarcoidosis. Serum insulin-like growth factor-I (IGF-I) and IGF-II were measured by RIA. Serum visfatin and free IGF-I were by ELISA. A high molecular weight form of IGF-II, termed "big" IGF-II, was identified by Western blotting. Tissue IGF-I was quantified by real time RT-PCR after RNA extraction. Before operation, total and free serum IGF-I, serum IGF-II and serum visfatin were within reference range. Big IGF-II was not detected in patient's serum extract. After operation, hypoglycemia did not recur and serum insulin returned to normal, while serum IGF-I decreased by half the preoperative level. RT-PCR revealed that mRNA level of IGF-I in the sarcoidosis tissue was about 1.8-fold greater than that in the normal spleen tissue. These data suggest that ectopic secretion of IGF-I by the splenic sarcoidosis and its direct access to the liver via the portal vein might cause fasting hypoglycemia mainly by suppressing hepatic gluconeogenesis.
  Endocrine Journal 01/2010; 57(4):325-30. · 2.03 Impact Factor
• Article: [Hypoglycemia due to ectopic secretion of insulin-like growth factor-I in a patient with an isolated sarcoidosis of the spleen].

  Yuiko Ogiwara, Seijiro Mori, Mizuki Iwama, Motoji Sawabe, Nobuo Kanazawa, Hikaru Furuta, Yoshiyuki Kimbara, Yoshiaki Tamura, Atsushi Araki, Hideki Ito
  Nihon Naika Gakkai Zasshi 11/2009; 98(11):2882-4.
• Source

  Available from: Hitoshi Shimano

  Article: Hormone-sensitive lipase deficiency suppresses insulin secretion from pancreatic islets of Lep ob/ob mice.

  Motohiro Sekiya, Naoya Yahagi, Yoshiaki Tamura, Hiroaki Okazaki, Masaki Igarashi, Keisuke Ohta, Mikio Takanashi, Masayoshi Kumagai, Satoru Takase, Makiko Nishi, [......], Ken Ohashi, Yoko Iizuka, Hiroaki Yagyu, Takanari Gotoda, Ryozo Nagai, Hitoshi Shimano, Nobuhiro Yamada, Takashi Kadowaki, Shun Ishibashi, Jun-ichi Osuga
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  ABSTRACT: It has long been a matter of debate whether the hormone-sensitive lipase (HSL)-mediated lipolysis in pancreatic beta-cells can affect insulin secretion through the alteration of lipotoxicity. We generated mice lacking both leptin and HSL Lep(ob/ob)/HSL(-/-) and explored the role of HSL in pancreatic beta-cells in the setting of obesity. Lep(ob/ob)/HSL(-/-) developed elevated blood glucose levels and reduced plasma insulin levels compared with Lep(ob/ob)/HSL(+/+) in a fed state, while the deficiency of HSL did not affect glucose homeostasis in Lep(+/+) background. The deficiency of HSL exacerbated the accumulation of triglycerides in Lep(ob/ob) islets, leading to reduced glucose-stimulated insulin secretion. The deficiency of HSL also diminished the islet mass in Lep(ob/ob) mice due to decreased cell proliferation. In conclusion, HSL affects insulin secretary capacity especially in the setting of obesity.
  Biochemical and Biophysical Research Communications 08/2009; 387(3):511-5. · 2.48 Impact Factor
• Article: Implications of measuring soluble receptor activators of nuclear factor-kappaB ligand and osteoprotegerin in bone metabolism of elderly women.

  Yuko Chiba, Tsuneko Onouchi, Toru Ikeda, Junichiro Adachi, Yoshiaki Tamura, Toshiyuki Horiuchi
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  ABSTRACT: The discovery of a signaling system consisting of a soluble receptor activator of the NF-kappaB ligand (sRANKL) and its decoy receptor osteoprotegerin (OPG) has provided a valuable key to understanding the pathophysiology of the bone microenvironment. We conducted a cross-sectional study of the role of sRANKL and OPG levels as they relate to bone metabolism in elderly postmenopausal women with and without osteoporosis. Fifty-one elderly women with or without osteoporosis were enrolled in the study. Bone alkaline phosphatase, osteocalcin, urinary deoxypyridinoline and urinary type I collagen N-terminal telopeptide (NTx) were measured as bone metabolic markers. Serum levels of OPG and sRANKL were measured by sandwich enzyme-linked immunosorbent assay and the lumbar spine bone mineral density (LSBMD) with dual-energy X-ray absorptiometry. Furthermore, we compared the sRANKL and OPG levels in elderly women with and without vertebral fractures (VFs). In elderly postmenopausal women, there was a significant positive association between OPG levels and the T score and Z score of LSBMD (r = 0.345 and p = 0.014 for T score; r = 0.438 and p = 0.001 for Z score). sRANKL levels were not significantly correlated with T score, Z score of LSBMD, or any of the four bone metabolic markers. There were no significant differences in the sRANKL levels among the three groups (normal bone mineral density, osteopenia, and osteoporosis), but a trend toward a higher value in the osteoporosis group. The sRANKL/OPG ratio was negatively correlated with the T score and Z score of LSBMD (r = -0.336, p = 0.017; r = -0.384, p = 0.006, respectively), but not with any of the four bone metabolic markers. OPG levels in elderly women with VFs were lower than in those without VFs (p = 0.05). Multiple regression analysis showed that OPG and NTx are contributing factors to bone loss in elderly women (p = 0.014 and 0.012, respectively). The OPG level provides a good predictor of osteoporosis as well as NTx in elderly women; additionally, the findings suggest that OPG might protect elderly women from bone loss or fractures.
  Gerontology 02/2009; 55(3):275-80. · 2.78 Impact Factor
• Article: [A case of nasal NK/T cell lymphoma presenting with bilateral giant adrenal tumors].

  Ayumi Toba, Yoshiaki Tamura, Yuko Osajima, Yoshiyuki Kinbara, Michiko Sato, Ryonosuke Yamaga, Ryo Hashimoto, Seijiro Mori, Shigezaburo Miyakoshi, Masatoshi Ota, Hideki Ito, Atsushi Araki
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  ABSTRACT: A 76-year-old woman presented to a clinic with fever and loss of body weight. Abdominal echogram showed bilateral adrenal swelling (left adrenal 90x80 mm, right adrenal 50x20 mm) and she was admitted to the hospital for further examination. A tumor was also found inside nasal cavity by enhanced computed tomography (CT), and abnormal uptake in the nasal cavity and adrenal gland was shown in gallium scintigraphy. Laboratory tests revealed the elevation of lactate dehydrogenase (LDH) and sIL-2R. Biopsy of the nasal tumor revealed nasal natural killer or thymus-derived (NK/T) cell lymphoma. No Epstein-Barr virus (EBV) -encoded RNA was detected in tissue. After THP-COP chemotherapy regimen, both the nasal and adrenal tumors decreased in size. However, a CT scan taken on admission revealed a pulmonary embolism. After treatment with heparin and warfarin, emboli disappeared. Chemotherapy was continued, but perforation of the small intestine occurred. Since the prognosis was poor, no operation was performed. Her condition slowly, and she died 60 days after admission. Since she had a high level of plasma ACTH (158.0 pg/ml) and normal serum cortisol (14.6 microg/dl), partial adrenal insufficiency was suspected. In addition, since her cortisol circadian rhythm was lost and cortisol levels were not completely suppressed by the 1 mg and 8 mg dexamethasone test, she met the criteria of the diagnosis of preclinical Cushing syndrome. NK/T cell lymphoma with giant adrenal tumor is extremely rare, but should be considered as one of the differential diagnoses of bilateral adrenal tumor.
  Nippon Ronen Igakkai Zasshi Japanese Journal of Geriatrics 12/2008; 45(6):660-5.
• Article: [The implementation of personalized treatment for osteoporosis].

  Seijiro Mori, Yuko Chiba, Seizo Yamamoto, Takayuki Hosoi, Toshiyuki Horiuchi, Fumi Kamimiya, Yoshiaki Tamura, Atsushi Araki, Hideki Ito
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  ABSTRACT: To establish personalized treatment of osteoporosis. A T869-->C polymorphism in exon 1 of the transforming growth factor-beta1 gene, which results in a Leu-->Pro substitution at amino acid 10, is reported to be associated with the rate of bone loss as well as the response to active vitamin D treatment. Therefore, we determined this single nucleotide polymorphism (SNP) to estimate the need of active vitamin D treatment. We also determined serum level of 25 hydroxy-vitamin D to evaluate a degree of vitamin D fulfillment. Based on these data, we categorized postmenopausal patients into four groups; C homozygote with vitamin D deficiency patients to whom 1 microg/day active vitamin D was administered, C homozygote without vitamin D deficiency patients or those who bore at least one T-allele with vitamin D deficiency to whom 0.5 microg/day active vitamin D was administered, and patients who bore at least one T-allele without vitamin D deficiency to whom no drug was given. The patients were checked up every 6 months with regard to changes in bone mineral density and occurrence of fresh fractures. The SNP was associated with prevalent vertebral fractures; the frequency of the T allele was significantly greater in patients with vertebral fractures. Furthermore, the serum level of 25 hydroxy-vitamin D was significantly lower in patients with vertebral fractures, which were observed in 17 out of 34 patients who bore at least one T-allele as well as vitamin D deficiency, while only 2 of 15 homozygous C-allele carriers without vitamin D deficiency suffered from fractures. These findings suggest that the SNP in combination with the serum level of 25 hydroxy-vitamin D can predict fracture risk in postmenopausal osteoporosis.
  Nippon Ronen Igakkai Zasshi Japanese Journal of Geriatrics 11/2008; 45(6):655-9.
• Article: Identification of neutral cholesterol ester hydrolase, a key enzyme removing cholesterol from macrophages.

  Hiroaki Okazaki, Masaki Igarashi, Makiko Nishi, Motohiro Sekiya, Makiko Tajima, Satoru Takase, Mikio Takanashi, Keisuke Ohta, Yoshiaki Tamura, Sachiko Okazaki, Naoya Yahagi, Ken Ohashi, Michiyo Amemiya-Kudo, Yoshimi Nakagawa, Ryozo Nagai, Takashi Kadowaki, Jun-ichi Osuga, Shun Ishibashi
  [show abstract] [hide abstract]
  ABSTRACT: Unstable lipid-rich plaques in atherosclerosis are characterized by the accumulation of macrophage foam cells loaded with cholesterol ester (CE). Although hormone-sensitive lipase and cholesteryl ester hydrolase (CEH) have been proposed to mediate the hydrolysis of CE in macrophages, circumstantial evidence suggests the presence of other enzymes with neutral cholesterol ester hydrolase (nCEH) activity. Here we show that the murine orthologue of KIAA1363, designated as neutral cholesterol ester hydrolase (NCEH), is a microsomal nCEH with high expression in murine and human macrophages. The effect of various concentrations of NaCl on its nCEH activity resembles that on endogenous nCEH activity of macrophages. RNA silencing of NCEH decreases nCEH activity at least by 50%; conversely, its overexpression inhibits the CE formation in macrophages. Immunohistochemistry reveals that NCEH is expressed in macrophage foam cells in atherosclerotic lesions. These data indicate that NCEH is responsible for a major part of nCEH activity in macrophages and may be a potential therapeutic target for the prevention of atherosclerosis.
  Journal of Biological Chemistry 10/2008; 283(48):33357-64. · 4.77 Impact Factor
• Article: Hormone-sensitive lipase is involved in hepatic cholesteryl ester hydrolysis.

  Motohiro Sekiya, Jun-Ichi Osuga, Naoya Yahagi, Hiroaki Okazaki, Yoshiaki Tamura, Masaki Igarashi, Satoru Takase, Kenji Harada, Sachiko Okazaki, Yoko Iizuka, Ken Ohashi, Hiroaki Yagyu, Mitsuyo Okazaki, Takanari Gotoda, Ryozo Nagai, Takashi Kadowaki, Hitoshi Shimano, Nobuhiro Yamada, Shun Ishibashi
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  ABSTRACT: Hormone-sensitive lipase (HSL) regulates the hydrolysis of acylglycerol and cholesteryl ester (CE) in various organs, including adipose tissues. However, the hepatic expression level of HSL has been reported to be almost negligible. In the present study, we found that mice lacking both leptin and HSL (Lep(ob/ob)/HSL(-/-)) showed massive accumulation of CE in the liver compared with Lep(ob/ob)/HSL(+/+) mice, while triacylglycerol (TG) accumulation was modest. Similarly, feeding with a high-cholesterol diet induced hepatic CE accumulation in HSL(-/-) mice. Supporting these observations, we detected significant expression of protein as well as mRNA of HSL in the liver. HSL(-/-) mice showed reduced activity of CE hydrolase, but not of TG lipase, in the liver compared with wild-type mice. Furthermore, we confirmed the expression of HSL in viable parenchymal cells isolated from wild-type mice. The hepatocytes from HSL(-/-) mice showed reduced activity of CE hydrolase and contained more CE than those from HSL(+/+) mice even without the incubation with lipoproteins. Incubation with LDL further augmented the accumulation of CE in the HSL-deficient hepatocytes. From these results, we conclude that HSL is involved in the hydrolysis of CE in hepatocyes.
  The Journal of Lipid Research 09/2008; 49(8):1829-38. · 5.56 Impact Factor
• Article: Primary aldosteronism due to unilateral adrenal microadenoma in an elderly patient: efficacy of selective adrenal venous sampling.

  Yoshiaki Tamura, Jun-Ichiro Adachi, Yuko Chiba, Seijiro Mori, Kazuhiro Takeda, Yutaka Kasuya, Takeo Murayama, Motoji Sawabe, Hironobu Sasano, Atsushi Araki, Hideki Ito, Toshiyuki Horiuchi
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  ABSTRACT: We encountered a case of drug-resistant hypertension and hypokalemia. Laboratory data suggested primary aldosteronism (PA). Computed tomography imaging appeared normal for a long duration with a left-sided nodule appearing far later; adrenal scintigraphy was first normal, and the second test showed right-sided uptake. However, a repeat selective adrenal venous sampling (SAVS) indicated a left-sided lateralization of the hypersecretion of aldosterone. Left adrenectomy was performed, and his clinical symptoms improved. The histopathological findings demonstrated the aldosterone-producing microadenoma with secondary micronodules. In conclusion, SAVS should be performed to determine the laterality of PA with obscure CT imaging.
  Internal Medicine 02/2008; 47(1):37-42. · 0.94 Impact Factor
• Article: Marked improvement of psychiatric symptoms after parathyroidectomy in elderly primary hyperparathyroidism.

  Yuko Chiba, Katsuhiko Satoh, Satoshi Ueda, Nobuo Kanazawa, Yoshiaki Tamura, Toshiyuki Horiuchi
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  ABSTRACT: Psychosomatic symptoms in primary hyperparathyroidism (PHPT) are various and include such conditions as obsessive-compulsive disorder, depression, anxiety, and paranoia. In the elderly the clinical features of the disease are often non-specific and difficult to diagnose. To quantify subjective symptoms of patients with hyperparathyroidism in the elderly, we determined whether these clinical manifestations resolved after surgical parathyroidectomy (PTX) in three PHPT patients over eighty years old. They were diagnosed with hypercalcemia, hypophosphatemia, high PTH concentrations, and osteoporosis. A single parathyroid adenoma was confirmed in each patient by Tc-MIBI scintigram, neck ultrasonography and computed tomographic scanning. PTX was performed in these three patients. Assessments of psychologic symptoms, using the Hamilton Rating Scale for Depression (HAM-D), serum calcium, and intact PTH were obtained before and after PTX. Mean weight of the resected adenomas was 438 +/- 138 mg (mean +/- SD). After PTX, serum calcium decreased from 11.1 +/- 0.5 to 9.2 +/- 0.5 mg/dl and intact PTH from 160.0 +/- 25.2 to 45.3 +/- 22.2 pg/ml. Total HAM-D scores in each patient decreased from 45 to 9, 17 to 1 and 15 to 5, respectively. Especially, there were marked improvements in depressive mood, psychomotor inhibition, anxiety and somatic symptoms after PTX. The quality of life in those patients was also improved by PTX. We propose here that PTX in elderly PHPT patients with psychiatric symptoms should be considered instead of oral administration, such as anti-depressants or bisphosphonates.
  Endocrine Journal 07/2007; 54(3):379-83. · 2.03 Impact Factor
• Article: [A case of Plummer disease that appeared in older old age after 10-year course of subclinical hyperthyroidism].

  Takashi Hasegawa, Atsushi Araki, Yoshiaki Tamura, Tomoki Sugawara, Akiko Iwata, Fumi Kamimiya, Yuko Chiba, Toshiyuki Horiuchi, Seijiro Mori, Hideki Ito
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  ABSTRACT: A 81-year-old woman with a thyroid tumor and subclinical hyperthyroidism since ten years ago was admitted to our hospital for palpitations and hyperthyroidism (FT(4) 1.75 ng/dl, FT(3) 5.37 pg/ml, TSH<0.03 microIU/ml). Although thyroid stimulating antibody (TSAb) was transiently and mildly positive, anti-TSH receptor antibody (TRAb), microsome test, and thyroid test were negative. Thyroid echogram showed an isoechoic nodule in the left lobe (33 x 42 x 22 mm) and a small nodule (10 x 15 x 9 mm) in right lobe. Thyroid scintiscan showed a hyperfunctional (hot) nodule in left thyroid lobe with suppressed uptake in the remainder of the gland. The uptake rate of thyroidal radioiodine ((123)I) in 24 hours was within the normal range (7.3%). Based on the above findings, a diagnosis of Plummer disease was made. Since she refused invasive surgical or radioiodine treatment, she was treated with 10 mg thiamazole daily. After treatment with propranolol and thiamazole, the thyrotoxic symptoms disappeared and thyroid function returned to normal level. She had osteoporosis but she had neither atrial fibrillation nor cardiac symptoms. This was a rare case of Plummer disease that appeared in extremely old age after a long course of subclinical hyperthyroidism.
  Nippon Ronen Igakkai Zasshi Japanese Journal of Geriatrics 03/2007; 44(2):251-5.
• Article: Postprandial reactive hypoglycemia in an oldest-old patient effectively treated with low-dose acarbose.

  Yoshiaki Tamura, Atsushi Araki, Yuko Chiba, Toshiyuki Horiuchi, Seijiro Mori, Takayuki Hosoi
  [show abstract] [hide abstract]
  ABSTRACT: We recently encountered a 96-year-old Japanese woman who suffered from frequent hypoglycemia. Endocrinological and imaging data eliminated the possibility of insulinoma, whereas oral glucose tolerance testing revealed impaired glucose tolerance and subsequent reactive hypoglycemia. The patterns between insulin or C-peptide secretions and glucose excursions demonstrated that the discrepancy occurred in the late postprandial stage. Administration of small doses of alpha-glucosidase inhibitor (alpha-GI) dramatically inhibited the rapid rise and subsequent precipitous fall of plasma glucose. Reactive hypoglycemia may be one of the important cause of hypoglycemia in the elderly, and alpha-GI could effectively and safely prevent such hypoglycemic attacks in those patients.
  Endocrine Journal 01/2007; 53(6):767-71. · 2.03 Impact Factor
• Source

  Available from: cof.org.cn

  Article: Remarkable increase in lumbar spine bone mineral density and amelioration in biochemical markers of bone turnover after parathyroidectomy in elderly patients with primary hyperparathyroidism: a 5-year follow-up study.

  Yoshiaki Tamura, Atsushi Araki, Yuko Chiba, Seijiro Mori, Takayuki Hosoi, Toshiyuki Horiuchi
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  ABSTRACT: We evaluated the efficacy of parathyroidectomy (PTX) on bone mineral density (BMD) and hormonal and biochemical markers of bone metabolism in elderly primary hyperparathyroidism (PHPT) patients, and followed these patients for 5 years after PTX. Eleven PHPT patients were enrolled and were followed for 5 years by measuring lumbar spine BMD (LSBMD), femoral BMD (FBMD), radial BMD (RBMD), parathyroid hormone (PTH), 1,25-dihydroxyvitamin D [1,25(OH)(2)D], serum calcium (SCa), inorganic phosphate (iP), bone-specific alkaline phosphatase (BAP), intact osteocalcin (IOC), urinary excretion of type I collagen cross-linked N-telopeptide (NTx), and urinary deoxypyridinoline (DPD). PTX produced significant increases in LSBMD of 12%, 19%, and 29% as compared with pretreatment levels after 1, 3, and 5 years, respectively (P < 0.01, compared to baseline), whereas there was no significant increase in FBMD and a slight decrease in RBMD. SCa and iP levels remained normal over the five years. PTX also resulted in significant decreases in PTH, 1,25(OH)(2)D, BAP, IOC, NTx, and DPD that continued for at least 3 years after PTX. In conclusion, PTX seemed effective to normalize various markers of bone metabolism in elderly PHPT patients and is recommended to patients with low LSBMD to prevent future fractures. On the other hand, the use of PTX for low FBMD or RBMD patients requires further discussion.
  Journal of Bone and Mineral Metabolism 01/2007; 25(4):226-31. · 2.27 Impact Factor