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Yoshihiro Ogawa

Publications and source records attributed to Yoshihiro Ogawa.

At least 19 recordsLinked to original sources
PubMed2025

A consensus guide to preclinical indirect calorimetry experiments.

Understanding the complex factors influencing mammalian metabolism and body weight homeostasis is a long-standing challenge requiring knowledge of energy intake, absorption and expenditure. Using measurements of respiratory gas exchange, indirect calorimetry can provide non-invasive estimates of whole-body energy expenditure. However, inconsistent measurement units and flawed data normalization methods have slowed progress in this field. This guide aims to establish consensus standards to unify indirect calorimetry experiments and their analysis for more consistent, meaningful and reproducible results. By establishing community-driven standards, we hope to facilitate data comparison across research datasets. This advance will allow the creation of an in-depth, machine-readable data repository built on shared standards. This overdue initiative stands to markedly improve the accuracy and depth of efforts to interrogate mammalian metabolism. Data sharing according to established best practices will also accelerate the translation of basic findings into clinical applications for metabolic diseases afflicting global populations.

Calorimetry, Indirect↗
PubMed2007

Attenuation of obesity-induced adipose tissue inflammation in C3H/HeJ mice carrying a Toll-like receptor 4 mutation.

Obese adipose tissue is characterized by increased infiltration of macrophages, suggesting that they might represent an important source of inflammation. We have provided in vitro evidence that saturated fatty acids, which are released from hypertrophied adipocytes via the macrophage-induced adipocyte lipolysis, serve as a naturally occurring ligand for Toll-like receptor 4 (TLR4) to induce the inflammatory changes in macrophages. Here we show the attenuation of adipose tissue inflammation in C3H/HeJ mice carrying a functional mutation in the TLR4 gene relative to control C3H/HeN mice during a 16-week high-fat diet. We also find that adiponectin mRNA expression is significantly reduced by co-culture of hypertrophied 3T3-L1 adipocytes and C3H/HeN peritoneal macrophages, which is reversed, when co-cultured with C3H/HeJ peritoneal macrophages. This study provides in vivo evidence that TLR4 plays a role in obesity-related adipose tissue inflammation and thus helps to identify the therapeutic targets that may reduce obesity-induced inflammation and the metabolic syndrome.

Adipocytes↗
PubMed2007

[Lymphedema].

It is necessary to do treatment that centered on the compression therapy after examining the condition closely enough to treat the lymphedema (so-called malignant lymphedema) that developed by the progress of cancer. As the compression method, the method of using the elastic bandage is general, and, according to circumstances, the elastic stocking is used. Moreover, not only the patient but also the family feels and self care what is important. It is thought that the manual lymph drainage to affected limbs is also effective to think about the symptom reduction of affected limbs as palliative medicine because of the purpose is not to improve the edema.

Female↗
PubMed2006

Peg1/Mest in obese adipose tissue is expressed from the paternal allele in an isoform-specific manner.

Paternally expressed 1 (Peg1)/mesoderm specific transcript (Mest) is an imprinted gene, which is only transcribed from the paternal (father's) allele. In some human cancer tissues, an alternatively spliced variant of PEG1/MEST mRNA using a different promoter of a distinct first exon is expressed from both paternal and maternal alleles. We previously reported that Peg1/Mest expression was markedly up-regulated in obese adipose tissue in mice. Moreover, transgenic overexpression of Peg1/Mest in the adipose tissue resulted in the enlargement of adipocytes in size. Given the potential pathophysiologic relevance in obesity, we examined the nature of increased expression of Peg1/Mest in obese adipose tissue. In obese adipose tissue, expression of Peg1/Mest was increased, but not that of other imprinted genes tested. The transcription rate of Peg1/Mest was increased in obese adipose tissue. We found at least four isoforms of mouse Peg1/Mest generated by use of the alternative first exons. We also demonstrated that the abundantly expressed Peg1/Mest in obese adipose tissue retained monoallelic expression. This is the first report of monoallelic induction of Peg1/Mest in adult tissues.

Adipocytes↗
PubMed2006

Effect of acute activation of 5'-AMP-activated protein kinase on glycogen regulation in isolated rat skeletal muscle.

5'-AMP-activated protein kinase (AMPK) has been implicated in glycogen metabolism in skeletal muscle. However, the physiological relevance of increased AMPK activity during exercise has not been fully clarified. This study was performed to determine the direct effects of acute AMPK activation on muscle glycogen regulation. For this purpose, we used an isolated rat muscle preparation and pharmacologically activated AMPK with 5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR). Tetanic contraction in vitro markedly activated the alpha(1)- and alpha(2)-isoforms of AMPK, with a corresponding increase in the rate of 3-O-methylglucose uptake. Incubation with AICAR elicited similar enhancement of AMPK activity and 3-O-methylglucose uptake in rat epitrochlearis muscle. In contrast, whereas contraction stimulated glycogen synthase (GS), AICAR treatment decreased GS activity. Insulin-stimulated GS activity also decreased after AICAR treatment. Whereas contraction activated glycogen phosphorylase (GP), AICAR did not alter GP activity. The muscle glycogen content decreased in response to contraction but was unchanged by AICAR. Lactate release was markedly increased when muscles were stimulated with AICAR in buffer containing glucose, indicating that the glucose taken up into the muscle was catabolized via glycolysis. Our results suggest that AMPK does not mediate contraction-stimulated glycogen synthesis or glycogenolysis in skeletal muscle and also that acute AMPK activation leads to an increased glycolytic flux by antagonizing contraction-stimulated glycogen synthesis.

AMP-Activated Protein Kinases↗
PubMed2006

Efficacy and safety of leptin-replacement therapy and possible mechanisms of leptin actions in patients with generalized lipodystrophy.

BACKGROUND: Lack of leptin is implicated in insulin resistance and other metabolic abnormalities in generalized lipodystrophy; however, the efficacy, safety, and underlying mechanisms of leptin-replacement therapy in patients with generalized lipodystrophy remain unclear. METHODS: Seven Japanese patients with generalized lipodystrophy, two acquired and five congenital type, were treated with the physiological replacement dose of recombinant leptin during an initial 4-month hospitalization followed by outpatient follow-up for up to 36 months. RESULTS: The leptin-replacement therapy with the twice-daily injection dramatically improved fasting glucose (mean +/- SE, 172 +/- 20 to 120 +/- 12 mg/dl, P < 0.05) and triglyceride levels (mean +/- SE, 700 +/- 272 to 260 +/- 98 mg/dl, P < 0.05) within 1 wk. The leptin-replacement therapy reduced insulin resistance evaluated by euglycemic clamp method and augmented insulin secretion at glucose tolerance test with different responses between acquired and congenital types. Improvement of the fatty liver was also observed. The efficacy and safety of the once-daily injection were comparable to those of the twice-daily injection. The leptin-replacement therapy ameliorated macro- and microalbuminuria and showed no deterioration of neuropathy and retinopathy of these patients. The leptin-replacement therapy is beneficial to diabetic complications and lipodystrophic ones. Two patients developed antileptin antibodies but not neutralizing antibodies. The therapy was well tolerated, and its effects were maintained for up to 36 months without any notable adverse effects such as hypoglycemia, high blood pressure, or reduction of bone mineral density. CONCLUSIONS: The present study demonstrates the efficacy and safety of the long-term leptin-replacement therapy and possible mechanisms of leptin actions in patients with generalized lipodystrophy.

Adolescent↗
PubMed2006

Role of the Toll-like receptor 4/NF-kappaB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages.

OBJECTIVE: Previous studies demonstrated that obese adipose tissue is characterized by increased infiltration of macrophages, suggesting that they might represent an important source of inflammation. Using an in vitro coculture system composed of 3T3-L1 adipocytes and RAW264 macrophages, we previously demonstrated that saturated fatty acids (FAs) and tumor necrosis factor (TNF)-alpha derived from adipocytes and macrophages, respectively, play a major role in the coculture-induced inflammatory changes. METHODS AND RESULTS: Coculture of adipocytes and macrophages resulted in the activation of nuclear factor-kappaB (NF-kappaB), a primary regulator of inflammatory responses, in both cell types. Pharmacological inhibition of NF-kappaB markedly suppressed the coculture-induced production of proinflammatory cytokines and adipocyte lipolysis. Peritoneal macrophages obtained from Toll-like receptor 4 (TLR4) mutant mice exhibited marked attenuation of TNFalpha production in response to saturated FAs. Notably, coculture of hypertrophied adipocytes and TLR4-mutant macrophages resulted in marked inhibition of proinflammatory cytokine production and adipocyte lipolysis. We also observed that endogenous FAs, which are released from adipocytes via the beta3-adrenergic stimulation, resulted in the activation of the TLR4/NF-kappaB pathway. CONCLUSIONS: These findings suggest that saturated FAs, which are released in large quantities from hypertrophied adipocytes via the macrophage-induced adipocyte lipolysis, serve as a naturally occurring ligand for TLR4, thereby inducing the inflammatory changes in both adipocytes and macrophages through NF-kappaB activation.

Adipocytes↗
PubMed2006

The utility of 18F-fluorodeoxyglucose positron emission tomography for early diagnosis of radiation-induced myocardial damage.

PURPOSE: We evaluated the clinical significance of focal increased uptake in the basal myocardium on F-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with esophageal cancer after radiotherapy. METHODS AND MATERIALS: Between August 2004 and July 2005, a total of 64 patients who had been irradiated for thoracic esophageal cancer underwent FDG-PET at least three months after the completion of chemoradiotherapy. Some patients showed increased FDG uptake in the basal portion of the myocardium. To clarify the clinical significance of these findings, further examinations of hearts were performed. The dose distribution in the myocardium with high FDG uptake was also analyzed retrospectively. RESULTS: Thirteen (20.3%) of the 64 patients showed high FDG uptake in the basal myocardium corresponding to the irradiated fields compared with FDG uptake in the myocardium outside the irradiated fields. Eight of the 13 patients consented to undergo examinations of the heart. Five of those eight patients showed low 123I-BMIPP uptake and four showed low 201TlCl uptake in the myocardium corresponding with high FDG uptake regions. In two patients, delayed enhancement was found in some parts of the area with high FDG uptake on Gd-DTPA magnetic resonance imaging (MRI), and the delay-enhanced lesion showed hypokinesia on cine-MRI in one patient. CONCLUSIONS: FDG-PET often shows focal increased uptake in the basal myocardium after radiotherapy for esophageal cancer. This finding indicates the possibility of radiation-induced cardiac damage, and cardiac function and symptoms of such patients should be followed carefully.

Aged↗
PubMed2006

Phase I trial of concurrent chemoradiation with weekly nedaplatin in patients with squamous cell carcinoma of the uterine cervix.

OBJECTIVE: This phase I clinical trial for cervical carcinoma had three objectives: to evaluate the toxicity of a concurrent chemoradiation regimen featuring weekly nedaplatin; to determine the recommended dose of nedaplatin for a phase II concurrent chemoradiation trial; and to evaluate the formula for predicting area under the curve data for nedaplatin through pharmacokinetic studies. PATIENTS AND METHODS: Twelve patients with locally advanced squamous cell carcinoma of the uterine cervix were enrolled. Nedaplatin was administered once a week for 6 weeks. The starting dose of nedaplatin was 25 mg/m(2)/week, with increments of 5 mg/m(2)/week planned for each dose level. Three cases were enrolled at each of the dose levels. Radiation therapy was delivered with both external beam teletherapy and intracavitary brachytherapy with HDR-RALS. Volunteering patients underwent pharmacokinetics studies during the second course. RESULTS: Nedaplatin at a dose of 25, 30, and 35 mg/m(2) was safely administered for three cases at each dose level. At a dose of 40 mg/m(2), however, all three cases had Grade 3 neutropenia. Observed area under the curve value and predicted value was closely correlated, with differences between the two area under the curve values within 25%. All 12 cases achieved a clinical complete response, as evaluated with RECIST. CONCLUSIONS: Our recommended dose for a phase II trial of concurrent chemoradiation with weekly nedaplatin is 35 mg/m(2). The formula can predict unbound concentration of nedaplatin based on area under the curve within 25% error.

Adult↗
PubMed2006

Concentrations and their ratio of (222)Rn decay products in rainwater measured by gamma-ray spectrometry using a low-background Ge detector.

The concentrations and the concentration ratios of individual short-lived (222)Rn decay products ((214)Pb and (214)Bi) in rainwater were measured at Kumatori village (34.39 degrees N, 135.35 degrees E, approximately 70 m above sea level) in Osaka, Japan, by gamma-ray spectrometry using a low-background Ge detector. The dependence of the time variations of the concentrations and their ratios on rainfall rate was investigated. It was observed that the concentrations were negatively correlated with the rainfall rate in some rainfall events, and that there was no clear correlation in other rainfall events. The changes in the dependence of the concentration on the rainfall rate occurred after the passage of a cold front during a single rainfall event. The concentration ratios showed a weak negative correlation with the rainfall rate for most of the observed rainfall events. A scavenging model was designed in this study in order to explain the observation results. Based on the relationship between the concentrations of (214)Pb and (214)Bi in the rainwater and the rainfall rate for an individual rainfall event, the increase in the environmental gamma-ray dose rate from (214)Pb and (214)Bi deposited on the ground was calculated, and the calculated increase agreed well with that observed by the in situ measurement on flat ground.

Air Pollutants, Radioactive↗
PubMed2006

Results of radiation therapy combined with nedaplatin (cis-diammine-glycoplatinum) and 5-fluorouracil for postoperative locoregional recurrent esophageal cancer.

BACKGROUND: Although the effectiveness of radiotherapy with concurrent administration of several anti-tumor drugs for postoperative recurrent esophageal cancer has been demonstrated, the results are not satisfactory. The purpose of the present study was to evaluate the effectiveness and safety of radiotherapy combined with nedaplatin and 5-FU for postoperative locoregional (excluding hematogenous metastasis) recurrent esophageal cancer. METHODS: In June 2000, we started a phase II study on treatment of postoperative locoregional recurrent esophageal cancer with radiotherapy (60 Gy/30 fr/6 weeks) combined with chemotherapy consisting of two cycles of nedaplatin (70 mg/m2/2 h) and 5-FU (500 mg/m2/24 h for 5 days). The primary endpoint of the present study was overall survival rate, and the second endpoints were irradiated-field control rate, tumor response and toxicity. RESULTS: A total of 30 patients were included in this study. The 1-year and 3-year overall survival rates were 60.6% and 56.3%, respectively, with a median survival period of 39.0 months, and the 1-year and 3-year irradiated-field control rates were 86.4% and 72%, respectively. Complete response and partial response were observed in 13.3% and 60.0% of the patients, respectively. Grade 3 or higher leukocytopenia and thrombocytopenia were observed in 30% and 3.3% of the patients, respectively, but renal toxicity of grade 3 or higher was not observed. The regimen was completed in 76.7% of the patients. In univariate analysis, the difference between survival rate in preradiotherapy performance status, recurrent pattern (worse for patients with anastomotic recurrence) and age (worse for younger patients) were statistically significant. CONCLUSION: Radiotherapy combined with nedaplatin and 5-FU is a safe and effective salvage treatment for postoperative locoregional recurrent esophageal cancer.

Aged↗
PubMed2006

The unified hypothesis of interactions among the bone, adipose and vascular systems: 'osteo-lipo-vascular interactions'.

Epidemiological evidence has established a link among hyperlipidemia, visceral obesity, osteoporosis, and cardiovascular diseases (CVD). We here propose the hypothesis that the associations of those disorders are based on interaction of the three organs, i.e. the bone, adipose, and vascular tissues, possibly through multiple interactions among several humoral factors and/or transcription factors. The unified hypothesis of three organs, which we call 'osteo-lipo-vascular interactions', may be explained by the common origin of the cells in each organ. The mesenchymal stem cells are capable of differentiating into osteoblasts, vascular smooth muscle cells, and adipocytes. Alternatively, macrophages may evolve into osteoclasts or infiltrate both the vascular and adipose tissues, thereby leading to chronic inflammation. This unified concept of three organs may provide insights into the development of a new drug for the treatment of osteoporosis, obesity, hyperlipidemia or CVD.

Adipose Tissue↗
PubMed2006

α2 isoform-specific activation of 5'adenosine monophosphate-activated protein kinase by 5-aminoimidazole-4-carboxamide-1-β-D-ribonucleoside at a physiological level activates glucose transport and increases glucose transporter 4 in mouse skeletal muscle.

5'Adenosine monophosphate-activated protein kinase (AMPK) has been implicated in exercise-induced stimulation of glucose metabolism in skeletal muscle. Although skeletal muscle expresses both the alpha1 and alpha2 isoforms of AMPK, the alpha2 isoform is activated predominantly in response to moderate-intensity endurance exercise in human and animal muscles. The purpose of this study was to determine whether activation of alpha2 AMPK plays a role in increasing the rate of glucose transport, promoting glucose transporter 4 (GLUT4) expression, and enhancing insulin sensitivity in skeletal muscle. To selectively activate the alpha2 isoform, we used 5-aminoimidazole-4-carboxamide-1-beta-d-ribonucleoside (AICAR), which is metabolized in muscle cells and preferentially stimulates the alpha2 isoform. Subcutaneous administration of 250 mg/kg AICAR activated the alpha2 isoform for 90 minutes, but not the alpha1 isoform in hind limb muscles of the C57/B6J mouse. The maximal activation of the alpha2 isoform was observed 30 to 60 minutes after administration of AICAR and was similar to the activation induced by a 30-minute swim in a current pool. The increase in alpha2 activity paralleled the phosphorylation of Thr(172), the essential residue for full kinase activation, and the activity of acetyl-coenzyme A carboxylase beta, a known substrate of AMPK in skeletal muscle. Subcutaneous injection of AICAR rapidly increased, by 30%, the rate of 2-deoxyglucose (2DG) transport into soleus muscle; 2DG transport increased within 30 minutes and remained elevated for 4 hours after administration of AICAR. Repeated intraperitoneal injection of AICAR, 3 times a day for 4 to 7 days, increased soleus GLUT4 protein by 30% concomitant with a significant 20% increase in insulin-stimulated 2DG transport. These data suggest that moderate endurance exercise promotes glucose transport, GLUT4 expression, and insulin sensitivity in skeletal muscle at least partially via activation of the alpha2 isoform of AMPK.

AMP-Activated Protein Kinases↗
PubMed2006

An alpha-glucosidase inhibitor, voglibose, reduces oxidative stress markers and soluble intercellular adhesion molecule 1 in obese type 2 diabetic patients.

Postprandial hyperglycemia and hyperlipidemia are considered risk factors for cardiovascular disease. This study was designed to elucidate whether improving the postprandial state by voglibose, an alpha-glucosidase inhibitor, leads to the reduction of oxidative stress markers and soluble adhesion molecules in obese type 2 diabetic patients. A total of 30 Japanese obese type 2 diabetic patients were randomly assigned and treated for 3 weeks with either diet alone (the control group) or diet plus voglibose (0.9 mg daily) (the voglibose group) (n=15 each). Analysis of the diurnal metabolic profiles revealed a significant reduction of postprandial hyperglycemia and hyperlipidemia in the voglibose group relative to the control group (P<.05), despite the similar improvement in body mass index and hemoglobin A(1c) in both groups. Voglibose also decreased significantly the plasma levels of soluble intercellular adhesion molecule 1 and urinary excretion of 8-iso-prostaglandin F(2)alpha and 8-hydroxydeoxyguanosine (P<.01) and C-reactive protein (P<.05) relative to the control group. In conclusion, this study represents the first demonstration that voglibose reduces oxidative stress generation and soluble intercellular adhesion molecule 1 in parallel with the reduction of postprandial hyperglycemia and hyperlipidemia in obese type 2 diabetic patients.

Adult↗
PubMed2006

Predictive factors for acute esophageal toxicity in thoracic radiotherapy.

Acute esophageal toxicity (AET) is a common complication and dose-limiting toxicity in thoracic radiotherapy. Previous studies demonstrated several clinical and dosimetric parameters of AET in patients with lung cancer. However, there are few reports dealing with these variables in intra-thoracic malignancies, including lung cancer and other thoracic malignancy. The purpose of this study was to evaluate the clinical and dosimetric factors associated with AET in patients with intra-thoracic malignancies. We examined 61 patients with intra-thoracic malignancies treated with radiotherapy: 34 patients with non-small-cell lung cancer (55%), 9 cases with small-cell lung cancer (15%), 7 cases with thymic cancer (11%), 4 thymomas (7%), 2 malignant lymphomas (3%), one seminoma (2%), one liposarcoma (2%), and 3 cases of other malignancies (5%). Radiotherapy was performed with a median dose of 60 Gray (Gy) (range 40-67 Gy). AET was graded according to the Radiation Therapy Oncology Group (RTOG) criteria. The following parameters were analyzed with respect to associations with AET by univariate and multivariate analyses: age, gender, thoracic surgery before radiotherapy, concurrent chemotherapy, duration of radiotherapy, maximum esophageal dose, mean esophageal dose, and percentage of esophageal volume receiving from 10 Gy (V10) to 65 Gy (V65), in 5-Gy increments. 43 patients (70%) developed AET: 36 patients (59%) with AET of RTOG Grade 1, 7 patients (11%) with Grade 2, and no patients (0%) with Grade 3 or worse. On multivariate analysis, V35 > 30% was the most statistically significant factor associated with mild AET (p = 0.013). Our findings provide a better understanding of the factors related to AET, and might be useful in designing a treatment plan to prevent severe esophageal toxicity.

Adult↗