Showing papers by "Ken Sugimoto published in 2011"

Salt-inducible kinase 1 influences Na(+),K(+)-ATPase activity in vascular smooth muscle cells and associates with variations in blood pressure.

Abstract: OBJECTIVES: Essential hypertension is a complex condition whose cause involves the interaction of multiple genetic and environmental factors such as salt intake. Salt-inducible kinase 1 (SIK1) is a sucrose-nonfermenting-like kinase isoform that belongs to the AMPK (5' adenosine monophosphate-activated protein kinase) family. SIK1 activity is increased by high salt intake and plays an essential role in regulating the plasma membrane Na,K-ATPase. The objective of this study was to examine whether SIK1 is present in vascular smooth muscle cells (VSMCs) and endothelial cells, whether it affects VSMC Na,K-ATPase activity and whether human SIK1 (hSIK1) represents a potential candidate for blood pressure regulation. METHODS: Localization of SIK1 was performed using immunohistochemistry, mRNA and western blot. Functional assays (Na,K-ATPase activity) were performed in VSMCs derived from rat aorta. Genotype-phenotype association studies were performed in three Swedish and one Japanese population-based cohorts. RESULTS: SIK1 was localized in human VSMCs and endothelial cells, as well as a cell line derived from rat aorta. A nonsynonymous single nucleotide polymorphism in the hSIK1 gene exon 3 (C→T, rs3746951) results in the amino acid change Gly→Ser in the SIK1 protein. SIK1-Ser was found to increase plasma membrane Na,K-ATPase activity in cultured VSMC line from rat aorta. Genotype-phenotype association studies in three Swedish and one Japanese population-based cohorts suggested that T allele (coding for Ser) was associated with lower blood pressure (P = 0.005 for SBP and P = 0.002 for DBP) and with a decrease in left ventricular mass (P = 0.048). CONCLUSION: The hSIK1 appears to be of potential relevance within VSMC function and blood pressure regulation.

Association between osteopontin promoter variants and diastolic dysfunction in hypertensive heart in the Japanese population.

Abstract: Heart failure with preserved ejection fraction is recently highlighted as a major health problem, and diastolic dysfunction associated with hypertension has a dominant role in the development of heart failure with preserved ejection fraction. Osteopontin (OPN) is a secreted phosphoprotein, which mediates fibrosis. In animal models, OPN is upregulated in response to pressure overload and is thought to be involved in systolic dysfunction. However, the functional role of OPN in diastolic dysfunction is unknown. The guanine base insertion polymorphism at −156 position of the OPN promoter is postulated to upregulate the transcription of OPN in human. To investigate whether −156del/G polymorphism of OPN promoter is associated with diastolic dysfunction in hypertensive hearts, the patients with hypertension have been genotyped for variants of −156del/G polymorphism by genomic sequencing. Diastolic function of the left ventricle was estimated as the ratio of early to atrial filling (E/A ratio), obtained by pulsed-Doppler derived transmitral flow in echocardiographic analysis. The patients with −156G allele displayed lower E/A ratio compared with those with −156del/del genotype, suggesting exacerbated diastolic function. Notably, in case of the population with diabetes mellitus, the patients with −156G allele showed significant association with lower E/A ratio, compared with −156del/−156del patients. Multiple linear regression analysis revealed that prevalence of −156G allele was an independent factor for lowering E/A ratio. The −156del/G genetic variants of OPN promoter were associated with decreased E/A ratio in hypertensive patients. These results suggest that OPN has a functional role in the development of diastolic dysfunction in hypertensive hearts.

Successful treatment of ulcerative colitis complicated by Sweet’s syndrome by corticosteroid therapy and leukocytapheresis

Abstract: Ulcerative colitis is occasionally complicated by dermatological disorders presenting as extra-intestinal manifestations, including erythema nodosum and pyoderma gangrenosum. Sweet’s syndrome is considered to be a rare cutaneous disease in patients with ulcerative colitis. To date, only 17 cases of Sweet’s syndrome complicating ulcerative colitis have been reported in the English literature. Here, we report a case of a 41-year-old male who had been suffering from ulcerative colitis for 20 years. He was admitted to hospital with hematochezia, diarrhea and fever, and painful erythematous nodules on the face and arms. Histological examination of skin biopsies showed inflammatory cell infiltration composed mainly of neutrophils without evidence of necrotizing vasculitis, and the condition was diagnosed as Sweet’s syndrome. The patient was treated with prednisolone and leukocytapheresis and the erythematous nodules on the skin, as well as the abdominal symptoms and endoscopic findings of ulcerative colitis, immediately improved. In this paper we report on this case and review the literature concerning ulcerative colitis and Sweet’s syndrome.

A case of eosinophilic gastroenteritis accompanied with fasciitis of the extremities

Abstract: We encountered a very rare case of eosinophilic gastroenteritis accompanied with fasciitis of the extremities. The patient was a 28-year-old woman with epigastralgia, eosinophilia plus leukocytosis, massive pleural effusion and ascites, and thickening of the walls of the intestine. Increase of the eosinophilic fraction in her ascites led to a diagnosis of eosinophilic gastroenteritis. She soon developed resting pain in all limbs and MRI revealed fasciitis. Prednisolone was effective in treating both gastroenteritis and fasciitis.