Publications (9)14.17 Total impact
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Article: Impact of serum retinol-binding protein 4 levels on regulation of remnant-like particles triglyceride in type 2 diabetes mellitus.
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ABSTRACT: Background. Although retinol-binding protein 4 (RBP4) associates with insulin resistance and remnant-like particles triglyceride (RLP-TG) elevated in the insulin resistant state, few data exist regarding the relationship between RBP4 and RLP-TG. Subjects and Methods. The study included 92 Japanese type 2 diabetic mellitus (T2DM) male patients (age 60.5 ± 13.6 years, body mass index (BMI) 24.7 ± 4.1 kg/m(2), waist circumference (WC) 88.4 ± 10.7 cm, and HbA1c (NGSP) 7.2 ± 1.9%). Patients on medications affecting insulin sensitivity, including fibrates, biguanides, and thiazolidinedione, were excluded. Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured by computed tomography. Results. RBP4 levels showed a significant positive correlation with RLP-TG (r = 0.2544 and P = 0.0056), TG (r = 0.1852 and P = 0.041), RLP-TG/TG (r = 0.23765 and P = 0.0241), and age (r = -0.2082 and P = 0.0219), although there was no significant correlation with VFA, SFA, adiponectin levels, or homeostasis model of assessment insulin resistance (HOMA-R). Multiple regression analysis revealed that RBP4 was an independent determinant of RLP-TG (P = 0.0193) but was not a determinant of TG. Conclusions. RBP4 correlates positively with serum RLP-TG independent of fat accumulation in T2DM. RBP4 may regulate remnant metabolism independent of glycemic control in T2DM.Journal of diabetes research. 01/2013; 2013:143515. -
Article: Investigations of IgG4-related disease involving the skin.
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ABSTRACT: OBJECTIVES: IgG4-related skin disease is not widely recognized. This prompted us to investigate the clinical and pathological features of five patients we encountered with IgG4-related disease (IgG4-RD) affecting the skin. METHODS: We investigated the clinical and pathological features of these five patients, including the distribution, onset, and morphology of eruptions, their pathological and immunohistochemical characteristics, and the occurrence of disease in other organs. RESULTS: The skin lesions were typically erythematous nodules and papules and brown papules like prurigo nodularis, which developed on the face or in the head and neck areas in four patients. Skin lesions were the first clinical manifestation in three patients. All five patients had sialadenitis and/or dacryoadenitis. The mean serum IgG4 concentration was 665.6 ± 410.0 mg/dl. Infiltrations of IgG4-positive plasma cells were observed in both the dermis and subcutaneous tissue. Germinal center formations were seen in three patients. Mild to moderate fibrosis was observed in all patients, and focal obliterative phlebitis in one. The average count of IgG4-positive cells was 67.3/high-power field (23.0-128.6). Wide variation in the numbers of infiltrating IgG4-positive cells was noted. CONCLUSION: IgG4-RD appears to have a distinctive clinicopathological presentation in the skin, differentiating it from other cutaneous disorders.Modern Rheumatology 11/2012; · 1.58 Impact Factor -
Article: Comparison of effects of bezafibrate and fenofibrate on circulating proprotein convertase subtilisin/kexin type 9 and adipocytokine levels in dyslipidemic subjects with impaired glucose tolerance or type 2 diabetes mellitus: results from a crossover study.
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ABSTRACT: Bezafibrate and fenofibrate show different binding properties against peroxisome proliferator-activated receptor subtypes, which could cause different clinical effects on circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and on various metabolic markers. An open, randomized, four-phased crossover study using 400 mg of bezafibrate or 200mg of fenofibrate was performed. Study subjects were 14 dyslipidemia with impaired glucose tolerance or type 2 diabetes mellitus (61 ± 16 years, body mass index (BMI) 26 ± 3 kg/m², total cholesterol (TC) 219 ± 53 mg/dL, triglyceride (TG) 183 ± 83 mg/dL, high-density lipoprotein-cholesterol (HDL-C) 46 ± 8 mg/dL, fasting plasma glucose 133 ± 31 mg/dL and HbA1c 6.2 ± 0.8%). Subjects were given either bezafibrate or fenofibrate for 8 weeks, discontinued for 4 weeks and then switched to the other fibrate for 8 weeks. Circulating PCSK9 levels and other metabolic parameters, including adiponectin, leptin and urine 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured at 0, 8, 12 and 20 weeks. Plasma PCSK9 concentrations were significantly increased (+39.7% for bezafibrate and +66.8% for fenofibrate, p<0.001) in all patients except for one subject when treated with bezafibrate. Both bezafibrate and fenofibrate caused reductions in TG (-38.3%, p<0.001 vs. -32.9%, p<0.01) and increases in HDL-C (+18.0%, p<0.001 vs. +11.7%, p<0.001). Fenofibrate significantly reduced serum cholesterol levels (TC, -11.2%, p<0.01; non-HDL-C, -17.3%, p<0.01; apolipoprotein B, -15.1%, p<0.01), whereas bezafibrate significantly improved glucose tolerance (insulin, -17.0%, p<0.05) and metabolic markers (γ-GTP, -38.9%, p<0.01; adiponectin, +15.4%, p<0.05; urine 8-OHdG/Cre, -9.5%, p<0.05). Both bezafibrate and fenofibrate increased plasma PCSK9 concentrations. The addition of a PCSK9 inhibitor to each fibrate therapy may achieve beneficial cholesterol lowering along with desirable effects of respective fibrates.Atherosclerosis 02/2011; 217(1):165-70. · 3.79 Impact Factor -
Article: IgG4-related skin lesions in a patient with IgG4-related chronic sclerosing dacryoadenitis and sialoadenitis.
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ABSTRACT: We describe a 60-year-old man with IgG4-related chronic sclerosing dacryoadenitis and sialoadenitis associated with lymphoplasmacytic and eosinophilic infiltration in erythematous nodules. Physical examination revealed left eye extrusion and small itchy nodules on the scalp and neck. The serum IgG level was 1,570 mg/dL, IgG4 463 mg/dL (29.5%), and IgE 4,554 IU/mL. Lacrimal gland biopsy disclosed prominent infiltrates of IgG4-positive plasma cells and scattered eosinophilic infiltrates with fibrosis, consistent with IgG4-related disease. A skin biopsy of a cutaneous nodule demonstrated that the infiltrated plasma cells around arterioles or venules in the deep dermis and subcutaneous fat tissue were strongly positive for IgG4. Although the swollen lacrimal and parotid gland and itchy subcutaneous erythematous nodules improved rapidly with oral prednisolone at a dose of 20 mg per day, the skin, lacrimal, and parotid lesions deteriorated simultaneously during steroid tapering and improved after increasing the dosage. As skin lesions are easy to biopsy, further study of the skin manifestations of IgG4-related disease will be important in further clarifying the clinical spectrum, pathophysiology and response to therapy of this disorder.Internal Medicine 01/2011; 50(14):1465-9. · 0.94 Impact Factor -
Article: Successful pregnancy and delivery in a patient with adult GH deficiency: role of GH replacement therapy.
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ABSTRACT: Adult growth hormone deficiency (AGHD) is a recently recognized endocrine disorder characterized by low peak GH levels during provocative tests. The AGHD has a negative impact on bone mineral density, skeletal muscle strength, physical capacity and psychosocial well-being. Furthermore, the girls with GHD have delayed pubertal development, and in adulthood present a condition of subfertility. Treatment for AGHD with GH replacement therapy has been officially approved since 2006 in Japan. The patient was diagnosed as pituitary dwarfism at age 9. She was treated with GH replacement therapy since diagnosis until her height reached 155cm at age 15. When she was 24 years old, she suffered from clinical symptoms relating to GH deficiency, and she visited our hospital for reintroduction of the therapy to alleviate these clinical symptoms. She has been treated with the replacement therapy since then. The patient's dysmenorrhea improved. And she was found to be 8 weeks pregnant at age 28 years 7 months. We immediately ceased replacement therapy and carefully observed the patient, because it is not indicated for female patient with pregnancy. She delivered a healthy girl at 40 weeks of pregnancy, no recognizable side-effects were observed in either mother or baby. To our knowledge, there are no other reports of a Japanese patient becoming pregnant during GH replacement therapy, and few cases have been reported in other countries. It remains uncertain whether the therapy is safe and essential for fetal development, fertility, and continuation of pregnancy in AGHD subjects.Endocrine Journal 10/2010; 58(1):65-8. · 2.03 Impact Factor -
Article: Three-dimensional CT images of high aortic occlusion associated with small aorta syndrome.
Case Reports 01/2009; 2009. -
Article: Relationships of serum haptoglobin concentration with HbA1c and glycated albumin concentrations in Japanese type 2 diabetic patients.
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ABSTRACT: The stable fractions of glycated hemoglobin (Hb), particularly HbA(1c), and glycated albumin (GA) were measured to monitor chronic glycemic control. Haptoglobin (Hp) is a Hb-binding protein, which plays a major role in preventing free Hb-induced tissue oxidative damage. The aim of this study was to clarify the relationships of serum Hp concentration with HbA(1c) and GA concentrations. A cross-sectional study to determine the relationship of serum Hp concentration with GA and HbA(1c) concentrations was conducted. The subjects were 125 Japanese type 2 diabetic patients with stable HbA(1c) levels for more than 3 consecutive months. Patients with altered albumin and red blood cell turnover, which are observed in those with chronic renal failure, liver cirrhosis, and anemia among others, were excluded from the study. Serum Hp concentration positively correlated with HbA(1c) concentration (r=0.30, p<0.001), but not with GA concentration (r=0.15, p=0.10). There was a weak inverse correlation between serum Hp concentration and GA/HbA(1c) ratio (r=-0.19, p=0.03). Moreover, GA /HbA(1c) ratio inversely correlated with body mass index (BMI) (r=-0.31, p<0.001). In contrast, there was no significant correlation between Hb concentration and HbA(1c) (r=0.01, p=0.88) or GA (r=0.12, p=0.21) concentrations. We also analyzed the correlation of serum Hp concentration with GA and HbA(1c) concentrations in patients with the Hp 2-1 and Hp 2-2 genotypes, separately. Hp concentration positively correlated with HbA(1c) concentration in patients with the Hp 2-1 (r=0.32, p=0.03) and Hp 2-2 (r=0.29, p=0.02) phenotypes. Multiple regression analysis revealed that the observed correlation between Hp and HbA(1c) concentrations was significant after adjustment for age, gender, and BMI. In contrast, there was no significant correlation between GA and Hp concentrations in patients with either phenotype. Then, we analyzed how Hp concentration affects GA/HbA(1c) ratio in patients with these Hp phenotypes. There was an inverse correlation between Hp concentration and GA/HbA(1c) ratio in patients with Hp 2-1 (r=-0.44, p=0.003), but not in those with Hp 2-2 (r=-0.03, p=0.75). Multiple regression analysis revealed that the inverse correlation between Hp concentration and GA/HbA(1c) ratio in patients with Hp 2-1 was independent of age, gender, and BMI. Hp phenotype and concentration should be considered in interpreting HbA(1c) and GA levels as glycemic control indicators in diabetic patients. We suggest that in type 2 diabetic patients with Hp 2-1 and high Hp concentrations, HbA(1c) level may be overestimated relative to GA level.Clinical Chemistry and Laboratory Medicine 12/2008; 47(1):70-4. · 2.15 Impact Factor -
Article: Decreased ADP-ribosyl cyclase activity in peripheral blood mononuclear cells from diabetic patients with nephropathy.
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ABSTRACT: ADP-ribosyl-cyclase activity (ADPRCA) of CD38 and other ectoenzymes mainly generate cyclic adenosine 5'diphosphate-(ADP-) ribose (cADPR) as a second messenger in various mammalian cells, including pancreatic beta cells and peripheral blood mononuclear cells (PBMCs). Since PBMCs contribute to the pathogenesis of diabetic nephropathy, ADPRCA of PBMCs could serve as a clinical prognostic marker for diabetic nephropathy. This study aimed to investigate the connection between ADPRCA in PBMCs and diabetic complications. PBMCs from 60 diabetic patients (10 for type 1 and 50 for type 2) and 15 nondiabetic controls were fluorometrically measured for ADPRCA based on the conversion of nicotinamide guanine dinucleotide (NGD(+)) into cyclic GDP-ribose. ADPRCA negatively correlated with the level of HbA1c (P = .040, R(2) = .073), although ADPRCA showed no significant correlation with gender, age, BMI, blood pressure, level of fasting plasma glucose and lipid levels, as well as type, duration, or medication of diabetes. Interestingly, patients with nephropathy, but not other complications, presented significantly lower ADPRCA than those without nephropathy (P = .0198) and diabetes (P = .0332). ANCOVA analysis adjusted for HbA1c showed no significant correlation between ADPRCA and nephropathy. However, logistic regression analyses revealed that determinants for nephropathy were systolic blood pressure and ADPRCA, not HbA1c. Decreased ADPRCA significantly correlated with diabetic nephropathy. ADPRCA in PBMCs would be an important marker associated with diabetic nephropathy.Experimental Diabetes Research 02/2008; 2008:897508. · 1.20 Impact Factor -
Article: Up-regulation of ras-GAP genes is reversed by a MEK inhibitor and doxorubicin in v-Ki-ras-transformed NIH/3T3 fibroblasts.
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ABSTRACT: Ras-GTPase-activating proteins (Ras-GAPs) have been implicated both as suppressors of Ras and as effectors in regulating cellular activities. To study whether Ras-GAPs have roles in tumor cell survival or not, mRNA levels of ras-related genes were measured in v-Ki-ras-transformed (DT) and the parental NIH/3T3 cells, using real-time PCR. mRNA levels of p120-Gap, Gap1(m), and PIK3CA were increased in DT cells compared with NIH/3T3 cells. p120-Gap and PIK3CA genes were induced by addition of serum or epidermal growth factor to serum-starved DT cells. Three anti-cancer drugs, an ERK kinase (MEK) inhibitor PD98059, a topoisomerase II poison doxorubicin (adriamycin), and a histone deacetylase inhibitor trichostatin A, selectively blocked the overexpression of p120-Gap and Gap1(m) genes in DT cells. These drugs also caused reversion of DT cells to the adherent shape associated with growth arrest. Our results suggest that p120-Gap and Gap1(m) genes provide important biomarkers for cancer therapies.Biochemical and Biophysical Research Communications 06/2007; 356(2):374-80. · 2.48 Impact Factor
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Institutions
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2009
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Kanazawa University
- Department of Internal Medicine
Kanazawa-shi, Ishikawa-ken, Japan
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