[Hyperglycemic hyperosmolar non-ketotic coma].
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Cerebral Infarction↗
Biomedical subjects
Masato Odawara
Publications and source records attributed to Masato Odawara.
Molecular analysis of the AGL gene: heterogeneity of mutations in patients with glycogen storage disease type III from Germany, Canada, Afghanistan, Iran, and Turkey.
Glycogen storage disease type III (GSD III) is an autosomal recessive disorder characterized by excessive accumulation of abnormal glycogen in the liver and/or muscles and caused by deficiency in the glycogen debranching enzyme (AGL). Previous studies have revealed that the spectrum of AGL mutations in GSD III patients depends on ethnic grouping. We investigated nine GSD III patients from Germany, Canada, Afghanistan, Iran, and Turkey and identified six novel AGL mutations: one nonsense (W255X), three deletions (1019delA, 3202-3203delTA, and 1859-1869del11-bp), and two splicing mutations (IVS7 + 5G > A and IVS21 + 5insA), together with three previously reported ones (R864X, W1327X, and IVS21 + 1G > A). All mutations are predicted to lead to premature termination, which abolishes enzyme activity. Our molecular study on GSD III patients of different ethnic ancestry showed allelic heterogeneity of AGL mutations. This is the first AGL mutation report for German, Canadian, Afghan, Iranian and Turkish populations.
Afghanistan↗
Use of hydroxy-methyl-glutaryl coenzyme A reductase inhibitors is associated with risk of lymphoid malignancies.
It has been speculated that the use of hydroxy-methyl-glutaryl coenzyme A reductase inhibitors (statins) is associated with the risk of malignant diseases. Considering their immunosuppressive activities, malignant diseases that are associated with an immunosuppressive status seem feasible to examine the association. We therefore examined the association between statin use and development of lymphoid malignancies in a case-control study. Cases were 221 consecutive incident cases with histopathologically proven lymphoid malignancies (lymphoma and myeloma), hospitalized in the Department of Hematology of Toranomon Hospital (Tokyo, Japan) between 1995 and 2001. Two independent control groups, comprising 442 and 437 inpatients without malignancies from the Departments of Orthopedics and Otorhinolaryngology of the same hospital, were selected to test for consistency of association. Controls were matched individually with cases for age, sex and year of admission. Subject information, including statin use, was abstracted from medical records at the time of hospitalization. Strength of association was evaluated as an adjusted odds ratios (aOR) using a conditional logistic regression model. A higher frequency of statin use was found among patients with lymphoid malignancies in comparison with both orthopedic (aOR 2.11, 95% CI 1.20-3.69, P = 0.009) and otorhinolaryngology patients (aOR 2.59, 95% CI 1.45-4.65, P = 0.001), the significance being maintained when the two control groups were combined (aOR 2.24, 95% CI 1.37-3.66, P = 0.001). In conclusion, we observed an elevated risk of lymphoid malignancy with statin use among Japanese patients. Further evaluations in different populations are required to draw conclusions as to the carcinogenicity of lymphoid malignancies with statin use.
Aged↗
[Therapeutic strategy for old age-onset diabetes mellitus].
Old-onset diabetes mellitus is often relatively mild in severity. However, if these patients develop marked hyperglycemia, they should be screened for the presence of malignancies, myocardial infarction and cerebral infarction. In addition, we should pay attention to the possible changes in the physical activities, medications and environmental status of the patients. There is no clear evidence how far we should lower blood glucose to prevent complications in those patients. Tight blood glucose control will, however, result in better prognosis in those patients with malignancies, myocardial or cerebral infarction. According to JDS, these patients are recommended to have less than 140 mg/dl of fasting plasma glucose and less than 7% of HbA1c. It is, however, necessary to respect the patient's will, efforts, and pride and is also necessary to adopt a flexible therapeutic strategy tailored to each patient's physical, psychological, and social status.
Age of Onset↗
Anticancer effects of phenoxazine derivatives combined with tumor necrosis factor-related apoptosis-inducing ligand on pancreatic cancer cell lines, KLM-1 and MIA-PaCa-2.
The aim of this study was to investigate the anticancer effects of the phenoxazine derivatives, 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3-one (Phx-1), 3-amino-1,4alpha-dihydro-4alpha,8-dimethyl-2H-phenoxazine-2-one (Phx-2), and 2-aminophenoxazine-3-one (Phx-3) on human pancreatic cancer cell lines, KLM-1 and MIA-PaCa-2, in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor superfamily of cytokines. Of these three phenoxazines, Phx-1 and Phx-3 inhibited proliferation of KLM-1 dose-dependently, but Phx-2 did not. Phx-3 caused both apoptosis and necrosis in KLM-1 cells, as evidenced by the phosphatidylserine externalization and propidium iodide permeable cells detected by a flow cytometric method using annexin-V and propidium iodide. Down-regulation of Bcl-2 expression appeared to be involved in the Phx-3-induced cell death. TRAIL did not affect proliferation of KLM-1, and the inhibitory effects of Phx-1 and Phx-3 on the KLM-1 cell line were not augmented by the combination with TRAIL. On the other hand, proliferation of the MIA-PaCa-2 cell line was not affected by Phx-1, Phx-2 and Phx-3, although it was significantly inhibited by TRAIL in a dose-dependent manner. Inhibitory effects of TRAIL on MIA-PaCa-2 were synergistically augmented by the addition of Phx-1 and Phx-3, but not by Phx-2. These results suggest that both Phx-1 and Phx-3 exert anticancer effects against human pancreatic cancer cells, KLM-1 and MIA-PaCa-2, through distinct action modes. Phx-1 and Phx-3 may be effective for the treatment of pancreatic cancer.
Antineoplastic Agents↗
2-amino-phenoxazine-3-one attenuates glucose-induced augmentation of embryonic form of myosin heavy chain, endothelin-1 and plasminogen activator inhibitor-1 in human umbilical vein endothelial cells.
The aim of this study was to investigate the changes in mRNA level of embryonic form of myosin heavy chain (SMemb), endothelin-1 (ET-1) and plasminogen activator inhibitor-1 (PAI-1), which are considered to be involved in the angiogenesis and atherosclerosis in diabetic blood vessels, in human umbilical vein endothelial cells (HUVECs) caused by high ambient glucose, and the effects of 2-aminophenoxazine-3-one (Phx-3), which was produced by the reaction of bovine hemoglobin with o-aminophenol, on them. The mRNA level of SMemb, ET-1 and PAI-1 and the level of SMemb protein were extensively upregulated in HUVECs treated with high concentration of glucose (15 mM), compared with those in the cells with normal concentration of glucose (5 mM). The migration activity of HUVECs evaluated by the cell migration assay was accelerated by 15 mM glucose. When 10 microM Phx-3, at the concentration of which the proliferation of HUVECs was not affected, was administered to HUVECs with 15 mM glucose, the mRNA level of SMemb, ET-1 and PAI-1 and the level of SMemb protein were significantly downregulated to the normal levels in the cells. However, when 10 microM Phx-3 was administered to HUVECs with 5 mM of glucose, the mRNA level of SMemb, ET-1 and PAI-1 and the level of SMemb protein were not affected. The migration activity of HUVECs, which was accelerated by high glucose, was reversed by 10 microM Phx-3. The present results suggest that Phx-3 may be a drug to prevent the high glucose-associated endothelial damage, vascular angiogenesis in diabetic patients, by inhibiting the expression of angiogenic factors, such as SMemb, ET-1 and PAI-1, in the endothelial cells.
Cells, Cultured↗
[Antigenic analysis of patients with asthma contracting by exposure to different species of pet hamsters].
BACKGROUND: Hamster-specific IgE antibodies as measured by currently available CAP-RAST tests are used to diagnose allergies associated with exposure to pet hamsters. Among patients with asthma attributed to hamsters, only about 60% are positive for hamster-specific IgE antibodies. We examined whether the results of CAP-RAST tests are related to differences in species-related antigens. METHODS: Currently available mixed specific IgE antibodies against European hamster and Golden hamster antigens (e84) were combined with Djungarian hamster epidermis to produce 3-species mixed specific antibodies. Correlations between results obtained with these mixed antibodies, those obtained with e84 and Djungarian hamster specific IgE antibody were examined in 20 patients with asthma who kept hamsters as pets. In addition, immunoblotting was used to analyze antigens in 9 patients. RESULTS: There was no correlation between results obtained with e84 and those obtained with Djungarian hamster antibody. Results obtained with 3-species mixed specific IgE antibodies positively correlated with those obtained with Djungarian hamster antibody. A specific binding protein for 67-kDa protein were found in patients who tested positive for e84 and Djungarian hamster antibody. A specific binding protein for 20-kDa protein were found in patients positive for only Djungarian hamster antibody. CONCLUSION: The main allergens differ among Golden hamsters, European hamsters, and dwarf Djungarian hamsters.
Adult↗
Molecular scanning of susceptibility genes for the development of coronary heart disease in Japanese.
Genetic predisposition has been implicated in the development of coronary heart disease (CHD). We made a molecular scanning of several genetic polymorphisms to see whether they are associated with CHD in Japanese patients with type 2 diabetes mellitus. Among several polymorphisms, only a polymorphism of paraoxonase gene was confirmed to be associated with CHD in this population. This polymorphism seems to be important in the development of CHD in Japanese as well as in Caucasian population.
Aryldialkylphosphatase↗
Association of the SNP-19 genotype 22 in the calpain-10 gene with elevated body mass index and hemoglobin A1c levels in Japanese.
BACKGROUND: An association of variations in the calpain-10 gene (CAPN10) with type 2 diabetes was originally reported in Mexican Americans. However, some studies in other racial groups were contradictory. METHODS: We studied the influence of genotypes and haplotype combinations (haplogenotypes) of CAPN10 on the metabolic traits in 286 Japanese subjects who visited a General Health Check-up Center. RESULTS: As for single nucleotide polymorphism (SNP)-19, subjects with genotype 22 had higher body mass index (BMI) and hemoglobin A(1c) (HbA(1c)) levels than those with genotypes 11 and 12 (p=0.003 and p=0.024, respectively). In SNP-63, subjects with genotype 11 had higher BMI and HbA(1c) levels than those with genotypes 12 and 22 (p=0.003 and p=0.045, respectively). Subjects who had genotype 22 at SNP-19 always had genotype 11 at SNP-63. Subjects with haplogenotype 121/121 had higher BMI levels (p=0.021) and tended to have higher HbA(1c) levels (p=0.08) than those with other haplogenotypes. All things considered, SNP-19 genotype 22, which was composed of haplogenotype 121/121 and 121/221, had highest significance level of association with elevated HbA(1c) levels. SNP-43 did not affect metabolic traits in our subjects. Subjects with haplogenotype 112/121 rather showed lower BMI and HbA(1c) levels (p=0.016 and p=0.008) than those with all other haplogenotypes. CONCLUSIONS: These results indicate the contribution of SNP-19 in CAPN10 to mild obesity and glucose intolerance in Japanese.
Blood Glucose↗
[Nateglinide and mitiglinide].
Patients with type 2 diabetes mellitus are associated with insulin resistance and/or impaired insulin secretion. Previous observations indicate that Japanese patients with type 2 diabetes tend to have impaired insulin response after glycemic load more often than Caucasian counterparts. Recently it has been reported that hyperglycemia after glucose load is itself a risk factor for the development of cardiovascular complications in the absence of elevated fasting plasma glucose. Recent observations on the association of post-challenge or post-prandial hyperglycemia with cardiovascular events suggest that lowering post-prandial plasma glucose may protect patients from developing cardiovascular diseases. Results of STOP-NIDDM trial suggest that nateglinide, which attenuates post-prandial glycemic surge in type 2 diabetes, may also be helpful for the protection against cardiovascular events. Nateglinide exerts its effects shortly after its administration and the effects continue for only about 3 hours. The patients receiving this agent rarely gain weight and develop hypoglycemia. This agent exerts hypoglycemic effects additively with alpha-gulucosidase inhibitors or metformin.
Cardiovascular Diseases↗
A patient with apolipoprotein E2 variant (Q187E) without lipoprotein glomerulopathy.
Four apolipoprotein (apo) E variants have been reported to be associated with lipoprotein glomerulopathy (LPG), which is characterized by type III hyperlipoproteinemia (type III HLP) and proteinuria and frequently leads to nephrotic syndrome. We report the histologic findings in the kidneys of a type III HLP patient with an apo E variant, apo E Toranomon, in which the glutamine at residue 187 in apo E is substituted by glutamic acid (Q187E). The patient also had type 2 diabetes mellitus. No evidence of lipoprotein thrombi suggestive of LPG was detected, however, and the histologic diagnosis was diabetic nephrosclerosis. This unique case illustrates that not all apo E variants result in LPG, and the location of mutations in the apo E protein is one of the important determinants for the development of LPG.
Apolipoproteins E↗
Mitochondrial gene abnormalities as a cause of psychiatric diseases.
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Adolescent↗
Association of HLA-DQ genotype in autoantibody-negative and rapid-onset type 1 diabetes.
OBJECTIVE: Some type 1 diabetic patients have a distinct phenotype characterized by the absence of pancreatic autoantibodies and fulminant clinical symptoms at onset, including marked hyperglycemia, severe diabetic ketoacidosis, and normal to near-normal HbA(1c) levels with complete destruction of beta-cells. However, little is known about genetic factors of this distinct subtype of diabetes (fulminant autoantibody-negative type 1 diabetes). RESEARCH DESIGN AND METHODS: We analyzed HLA-DQ genotypes in fulminant autoantibody-negative type 1 diabetes (n = 22) and autoantibody-positive type 1 diabetes (immune-mediated type 1 diabetes, n = 78) recruited from a cohort between 1980 and 2000. RESULTS: Fulminant autoantibody-negative type 1 diabetes had a significantly high prevalence of the HLA-DQA1*0303-DQB1*0401 haplotype in a homozygous manner (RR 39) or in a heterozygous manner with the HLA-DQA1*0302-DQB1*0303 haplotype (RR 13). In contrast, autoantibody-positive type 1 diabetic patients had a high prevalence of the HLA-DQA1*0302-DQB1*0303 haplotype in a homozygous manner (RR 10) or in a heterozygous manner with the HLA-DQA1*0303-DQB1*0401 haplotype (RR 12). CONCLUSIONS: Pathogenic roles of genotypic combinations of specific HLA-DQ haplotypes in a homozygous manner are suggested as causative mechanisms of aggressive beta-cell damage in a subtype of autoantibody-negative type 1 diabetes with fulminant clinical features.
Autoantibodies↗
Corticosteroid-responsive diabetes mellitus associated with autoimmune pancreatitis: pathological examinations of the endocrine and exocrine pancreas.
Histopathological changes of biopsied pancreata were examined in three diabetic patients with autoimmune chronic pancreatitis (ACP). We found intra- and periinsular mononuclear cell (MNC)-mainly CD8+ T cell-infiltration as well as MNC infiltration around the ductal cells. Islet beta cell volume decreased significantly. Some ductal cells expressed insulin and insulin promoter factor-1 concomitantly in the affected pancreas. These findings provide new insight toward understanding the pathological mechanisms of corticosteroid treatment-responsive diabetes associated with ACP.
Adrenal Cortex Hormones↗
[Evidence based treatment of dyslipidemia associated with diabetes mellitus].
Diabetic patients are more prone to develop atherosclerosis. Coronary heart disease (CHD), cerebrovascular disease(CVD), and peripheral arterial disease(PAD) are three main life-threatening macrovascular complications in diabetes. Previous studies indicate that glycemic control is important. They also indicate that glycemic control does not sufficiently prevent the development of atherosclerotic diseases in diabetic patients. It is now clear that treatment of dyslipidemia and hypertension are as important as good glycemic control. Diabetic patients tend to develop dyslipidemia and hypertension, as both derives from insulin resistance. Many randomized control studies have proved that lowering of LDL-cholesterol is beneficial for preventing the development of CHD or CVD. Sub-analyses of RCT of statins suggest that lipid lowering therapy helps prevent the development of these macrovascular complications.
Clinical Trials as Topic↗
[Secretion and metabolism of insulin].
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Amyloid↗
[Structure and function of islets of Langerhans].
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Animals↗