Matsubara T.,Integrated Center for Mass Spectrometry |
Matsubara T.,Shimadzu Corporation |
Kitazawa S.,Kobe University |
Kitazawa S.,Ehime University |
And 10 more authors.
Cell Metabolism | Year: 2012
Adipose tissue secretes adipokines that mediate insulin resistance, a characteristic feature of obesity and type 2 diabetes. By differential proteome analysis of cellular models of insulin resistance, we identified progranulin (PGRN) as an adipokine induced by TNF-α and dexamethasone. PGRN in blood and adipose tissues was markedly increased in obese mouse models and was normalized with treatment of pioglitazone, an insulin-sensitizing agent. Ablation of PGRN (Grn -/-) prevented mice from high fat diet (HFD)-induced insulin resistance, adipocyte hypertrophy, and obesity. Grn deficiency blocked elevation of IL-6, an inflammatory cytokine, induced by HFD in blood and adipose tissues. Insulin resistance induced by chronic administration of PGRN was suppressed by neutralizing IL-6 in vivo. Thus, PGRN is a key adipokine that mediates HFD-induced insulin resistance and obesity through production of IL-6 in adipose tissue, and may be a promising therapeutic target for obesity. © 2012 Elsevier Inc.
Hiki N.,Cancer Institute Hospital |
Kaminishi M.,Showa General Hospital |
Yasuda K.,Red Cross |
Uedo N.,Japan National Cardiovascular Center Research Institute |
And 8 more authors.
Digestive Endoscopy | Year: 2012
Aim: Peppermint oil solution was found to be effective for reducing gastric spasm during upper gastrointestinal endoscopy. The aim of the present study was to assess whether the gastric peristalsis-suppressing effect is dose-dependently induced by L-menthol, the major constituent of peppermint oil, and to determine the recommended dose of an L-menthol preparation. Methods: In this phase II, multicenter, double-blind, dose-response study, 131 eligible patients were randomly assigned to receive 20 mL of 0.4% L-menthol (n = 32), 0.8% L-menthol (n = 35), 1.6% L-menthol (n = 30), or placebo (n = 34). The primary efficacy measure was the proportion of subjects with no peristalsis in two time periods, 75 to 105 s after treatment and immediately before the completion of endoscopy. Results: The peristalsis-suppressing effect of L-menthol increased dose dependently (5.6%, 32.0%, 47.4% and 52.9% in the 0%, 0.4%, 0.8% and 1.6% groups, respectively: P < 0.001, one-tailed Cochran-Armitage trend test). As compared with the placebo group, the proportion of subjects with no peristalsis after administration was significantly higher in the 0.8% group (P = 0.015) and 1.6% group (P = 0.009). Adverse events in the L-menthol dose groups occurred with similar frequencies in the placebo group. Conclusion: L-menthol suppresses peristalsis in a dose-dependent manner, and the dose-response reaches a plateau at 0.8% L-menthol. Further Phase III studies are needed to establish the superiority of 0.8% L-menthol over placebo. © 2011 Japan Gastroenterological Endoscopy Society.
Tsukamoto Y.,Hyogo College of Medicine |
Nakata Y.,Chibune Hospital |
Futani H.,Hyogo College of Medicine |
Fukunaga S.,Hyogo College of Medicine |
And 2 more authors.
Pathology Research and Practice | Year: 2013
Clear cell sarcoma is a unique tumor which has EWSR1-ATF1 or EWSR1-CREB1 fusion. Several patterns of EWSR1-ATF1 fusion are observed in clear cell sarcoma. Since type 5-7 fusions were reported recently, they are classified as type 1-7. We examined EWSR1-ATF1 and EWSR1-CREB1 fusions in a single case of clear cell sarcoma with lung metastasis in a 36-year-old Japanese man. As a result, we found only type 1 EWSR1-ATF1 fusion in the primary site, but 4 types of EWS-ATF1 fusion (type 1, 2, 5, 6) were detected in the metastatic site. These 4 types of fusion were completely identical to the recent report, but the case had the same fusion patterns in both primary and metastatic sites. In our case, increased splicing activity in the EWSR1-ATF1 fusion might be acquired at the metastatic site. There is another possibility that metastasis might develop through the increased splicing activity in the fusion. © 2013 Elsevier GmbH.
Tateya S.,Kobe University |
Kim F.,University of Washington |
Tamori Y.,Kobe University |
Tamori Y.,Chibune Hospital
Frontiers in Endocrinology | Year: 2013
It has been demonstrated in rodents and humans that chronic inflammation characterized by macrophage infiltration occurs mainly in adipose tissue or liver during obesity, in which activation of immune cells is closely associated with insulin sensitivity. Macrophages can be classified as classically activated (M1) macrophages that support microbicidal activity or alternatively activated (M2) macrophages that support allergic and antiparasitic responses. In the context of insulin action, M2 macrophages sustain insulin sensitivity by secreting IL-4 and IL-10, while M1 macrophages induce insulin resistance through the secretion of proinflammatory cytokines, such as TNFα. Polarization of M1/M2 is controlled by various dynamic functions of other immune cells. It has been demonstrated that, in a lean state, TH2 cells, Treg cells, natural killer T cells, or eosinophils contribute to the M2 activation of macrophages by secreting IL-4 or IL-10. In contrast, obesity causes alteration of the constituent immune cells, in which TH1 cells, B cells, neutrophils, or mast cells induce M1 activation of macrophages by the elevated secretion of TNFα and IFNγ. Increased secretion of TNFα and free fatty acids from hypertrophied adipocytes also contributes to the M1 activation of macrophages. Since obesity-induced insulin resistance is established by macrophage infiltration and the activation of immune cells inside tissues, identification of the factors that regulate accumulation and the intracellular signaling cascades that define polarization of M1/M2 would be indispensable. Regulation of these factors would lead to the pharmacological inhibition of obesity-induced insulin resistance. In this review, we introduce molecular mechanisms relevant to the pathophysiology and review the most recent studies of clinical applications targeting chronic inflammation. ©2013 Tateya, Kim and Tamori.
Ooyama Y.,Chibune Hospital |
Okutani R.,Osaka City General Hospital |
Iguchi Y.,Socail Welfare Organization Saiseikai Imperial Gift Foudation Inc.
Anesthesia and Resuscitation | Year: 2012
Patients with Kuppel-Feil syndrome (KFS) frequently encounters difficulties with airway management including mask ventilation, as the disease causes skeletal abnormalities including fusion of 2 or more vertebrae. We report successful general anesthesia management on 5 separate occasions in a child complicated with KFS. A boy was delivered vaginally at 41 weeks of pregnancy (2,804 g), then developed tachypnea and cyanosis soon after birth. A total anomalous pulmonary venous connection (IIb), atrial septal defect, ventricular septal defect, and patent ductus arteriosus were found by echocardiography, and he was referred to our hospital at 4 days old. Tachypnea and labored respiration were improved by oral medical treatment. Furthermore, good body weight gain was seen and he was discharged from the hospital. At 6 months old, he underwent heart repair surgery, after which posterior spinal fusion (C7-T2) for marked spine deformity first noted at the age of 1 year was performed at 5 years old, and ear ventilation tube insertion surgery was done at 7, 8, and 9 years old. Each operation was performed under general anesthesia, which was managed safely without difficulties in regard to airway management.
Tamori Y.,Chibune Hospital |
Tamori Y.,Kobe University |
Takahashi T.,Chibune Hospital |
Suwa H.,Chibune Hospital |
And 6 more authors.
Internal Medicine | Year: 2010
An 80-year-old woman with type 2 diabetes was admitted due to right-handed muscle weakness. The patient presented with Brown-Sequard syndrome, with complete paralysis of the right lower limb along with a loss of pain and temperature sensations in the left lower limb. Magnetic resonance imaging revealed a cervical epidural abscess, and accompanying edema or inflammation of the right side of the spinal cord at the C5 level. She underwent drainage and evacuation of the spinal abscess, followed by intravenous antibiotic administration. These interventions ameliorated the neurological deficits. The present case suggests the importance of epidural abscess as a rare pathogenetic cause of Brown-Sequard syndrome in type 2 diabetes. © 2010 The Japanese Society of Internal Medicine.
Nakajima S.,Chibune Hospital |
Takahashi T.,Chibune Hospital |
Tanaka Y.,Chibune Hospital |
Nishimoto Y.,Chibune Hospital |
And 4 more authors.
Journal of the Japan Diabetes Society | Year: 2012
The patient was a 38-year old woman. She experienced epigastralgia on July 15,2011. She was admitted to a hospital with a diagnosis of acute pancreatitis on July 20. Her plasma glucose level was 92 mg/d/ at the time of admission. Although the acute pancreatitis was quickly resolved, nausea and general fatigue appeared on July 26. She was found to be in the fifth week of pregnancy, but she had a miscarriage the next day. She was discharged from the hospital on July 29, although the symptoms persisted. However, she was transported to this hospital on July 31, due to frequent vomiting that began the day after her discharge. Her plasma glucose level was 498 mg/d/ at the time of admission and she had ketoacidosis. She was admitted with a diagnosis of diabetic ketoacidosis. She was diagnosed to have fulminant type 1 diabetes based on her HbAlc level (6.0 %) and low serum and urinary levels of CPR. Fulminant type 1 diabetes is associated with acute pancreatitis and pregnancy. This is an instructive case of fulminant type 1 diabetes that developed during early pregnancy (fifth week) along with the preexisitng acute pancreatitis more than 10 days before the onset of hyperglycemia.
PubMed | Chibune Hospital
Type: Case Reports | Journal: Internal medicine (Tokyo, Japan) | Year: 2010
An 80-year-old woman with type 2 diabetes was admitted due to right-handed muscle weakness. The patient presented with Brown-Sequard syndrome, with complete paralysis of the right lower limb along with a loss of pain and temperature sensations in the left lower limb. Magnetic resonance imaging revealed a cervical epidural abscess, and accompanying edema or inflammation of the right side of the spinal cord at the C5 level. She underwent drainage and evacuation of the spinal abscess, followed by intravenous antibiotic administration. These interventions ameliorated the neurological deficits. The present case suggests the importance of epidural abscess as a rare pathogenetic cause of Brown-Sequard syndrome in type 2 diabetes.