The Tazuke Kofukai Foundation Medical Research Institute Kitano Hospital

Ōsaka, Japan

The Tazuke Kofukai Foundation Medical Research Institute Kitano Hospital

Ōsaka, Japan

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Koshiyama H.,The Tazuke Kofukai Foundation Medical Research Institute Kitano Hospital | Koshiyama H.,Kyoto University | Ogawa Y.,Tokyo Medical and Dental University | Tanaka K.,Kyoto University | And 2 more authors.
Medical Hypotheses | Year: 2010

Endocrine system has been considered to be a linear one, but the 'real world endocrine system' is a complex system, which is difficult to investigate using conventional strategies, such as single nucleotide polymorphism, genome-wide analysis, or gene targeting in animals. Here we propose a new strategy to comprehend the endocrine system as a complex network system. We introduced several novel concepts, such as complex system, network analysis, systems biology and evolutionary medicine, into the comprehension of endocrine system as a whole complex network system. This system is considered to be a scale-free network with key molecules such as acetyl CoA, NAD or ATP as 'hubs'. This system is robust against simple mutations, but various complex diseases may attack hubs. The system is also 'fractals', since there exist similar network systems among cells, proteins, and transcription factors in the lower levels, and there are similar ones among disease and social network in the higher levels. We propose to call this model 'Integrated Network Systems and Evolutionary DEvelopmental ENdocrinology (INS-EDEN)'. This novel framework will facilitate us to develop a new approach for understanding and treatment of various complex diseases related to endocrinology, and identify a unified theory of complex diseases. © 2009 Elsevier Ltd. All rights reserved.


PubMed | The Tazuke Kofukai Foundation Medical Research Institute Kitano Hospital
Type: Journal Article | Journal: Diabetic medicine : a journal of the British Diabetic Association | Year: 2012

It has been recognized that blood pressure shows a seasonal variation, but it remains unknown whether diabetic nephropathy shows a seasonal variation. In the present study, we investigated the change in urinary albumin/creatinine ratio in relation to the season in Japanese patients with Type 2 diabetes.A total of 430 subjects (275 male, 155 female) with Type 2 diabetes and early nephropathy (defined by UACR 30-300 mg/g creatinine) were included. One year was divided into four seasons and each season was defined as winter (December-February), spring (March-May), summer (June-August), and fall (September-November), and systolic and diastolic blood pressure, serum creatinine levels, and the urinary albumin/creatinine ratio were examined. The estimated glomerular filtration rate was also calculated and evaluated.The mean age ( SE) was 64.8 0.8 years. The mean systolic blood pressure was significantly higher in winter than in summer (136 0.68 vs. 133 0.68 mmHg, P < 0.001). The urinary albumin/creatinine ratio showed a significantly higher value in winter than in summer (72.8 4.4 vs. 54.6 3.4 mg/g creatinine, P < 0.001). The curve of seasonal variation of this ratio showed a similar change to that of systolic blood pressure. No significant seasonal variation was observed in estimated glomerular filtration rate and diastolic blood pressure.Our results suggest that there is a hitherto unknown seasonal variation in the urinary albumin/creatinine ratio, and that it may be necessary to consider this seasonal change, especially when performing an intervention study of nephropathy.


PubMed | The Tazuke Kofukai Foundation Medical Research Institute Kitano Hospital
Type: Case Reports | Journal: Internal medicine (Tokyo, Japan) | Year: 2011

A 49-year-old otherwise healthy man was admitted to our hospital because of repeated generalized convulsions after influenza A virus infection. His family history was notable for consanguinity of parents. Initial laboratory tests revealed metabolic alkalosis with hypomagnesemia, as well as an elevated high density lipoprotein cholesterol level. He was diagnosed with Gitelmans syndrome and cholesteryl ester transfer protein deficiency by identifying homozygous mutations of causative genes, SLC12A3 and CETP, respectively. These two genes are located in the vicinity on chromosome 16, suggesting the possibility of autozygosity. This is the first case report highlighting the co-existence of these genetic disorders.


PubMed | The Tazuke Kofukai Foundation Medical Research Institute Kitano Hospital
Type: Journal Article | Journal: Clinical drug investigation | Year: 2012

Telmisartan has been reported to have beneficial effects on insulin resistance and lipid profiles by acting as a peroxisome proliferator-activated receptor- (PPAR) agonist. In this study we investigated the relationship between telmisartan dose and glycaemic control in Japanese subjects with type 2 diabetes mellitus and hypertension.Patients (n = 263) who were prescribed telmisartan 20, 40 or 80 mg/day at our clinic were retrospectively identified from our clinical database. Only patients without changes in their treatments for diabetes and hypertension for 6 months after starting telmisartan were included in this study. Glycosylated haemoglobin A(1c) (HbA(1c)) levels were measured at 0, 3 and 6 months after starting telmisartan.At 3 and 6 months after starting telmisartan, HbA(1c) levels were significantly decreased in patients treated with telmisartan 40 or 80 mg/day but not in patients treated with telmisartan 20 mg/day (mean standard error change at 6 months: -0.29 0.10%, p < 0.001; -0.48 0.15%, p < 0.001; and -0.03 0.10%, p = 0.33; respectively). When patients were classified into two groups by telmisartan dose (20 vs 40 mg/day), there was no significant correlation between baseline HbA(1c) and change in HbA(1c) levels over time in the 20 mg/day group. However, in patients treated with 40 mg/day of telmisartan, baseline HbA(1c) was negatively correlated with the change in HbA(1c) at 6 months. Multiple regression analysis confirmed that baseline HbA(1c) and telmisartan dose were the predictive factors.Our results suggest that telmisartan influences glycaemic control in a dose-dependent manner; doses 40 mg/day may be needed to improve glycaemic control. Our data also suggest that patients with higher baseline HbA(1c) may experience greater improvements in glycaemic control with telmisartan.

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