SummaryTo investigate the effects of transforming growth factor-betas (TGF-βs) on endothelial anticoagulant activity, we assayed thrombomodulin (TM) activity and antigen levels of human umbilical vein endothelial cells (HUVECs) incubated with TGF-βs in vitro. TGF-β1 suppressed surface TM activity and surface TM antigen levels maximally 12 h after incubation in dose-dependent manners. TGF-β2 was almost equipotent with TGF-β1 for the suppression of them. Both TGF-βs suppressed total TM antigen level in HUVECs, and the time course of the suppression was similar to that of the cell surface TM antigen level. The maximal reductions of TM mRNA levels by TGF-βs were observed at several hours ahead of those observed in both surface and total TM antigen levels, suggesting that the TGF-β-mediated suppression of TM antigen of HUVECs is primarily regulated at the TM mRNA level. Our present work suggests that the down-modulation of TM level induced by TGF-βs in HUVECs contributes in vivo to promoting the thrombogenesis either at the sites of injury of vessel walls, such as atherosclerotic lesions where TGF-β1 is released from platelets, smooth muscle cells and monocytes, or at neovascular walls in tumors secreting TGF-β2.
The decrease in LPL protein mass could cause an increase in serum apo B-48 and RLP-TG levels, which is related to the retardation of remnant metabolism.
Abstract. We report two siblings, a 9-year-old boy and 4-year-old girl, with ACTH insensitivity. They were referred to our hospital because of pigmentation of the skin. They had normal plasma cortisol and urinary 17-OHCS levels despite markedly high plasma ACTH, and these did not respond to consecutive 3-day ACTH-Z administration, but plasma aldosterone responded normally to increased plasma renin activity after a low sodium diet. We examined the characteristics of ACTH receptors in peripheral blood mononuclear leukocytes (MNLs) obtained from the patients and their family. Adenylate cyclase generation caused by an addition of ACTH did not occur in MNLs from the patients.In studies on ACTH binding to MNLs, a lack of high-affinity ACTH binding was observed in the patients. These results suggest that the patients have a defect in ACTH binding to the receptors, resulting in ACTH insensitivity. The reason for this defect in ACTH binding remains unclear because no significant mutation in the ACTH receptor DNA sequence was detected in the MNLs of these patients.
We performed an epidemiologic study on the basis of a questionnaire survey of 162 children with end‐stage renal disease (ESRD). Sixty‐nine (43%) of our 162 children, including 25 detected at mass screening of urine, were found by chance hematuria and/or proteinuria. The three major causes of ESRD in our children were chronic glomerulonephritis (CGN) in 56, congenital anomalies of the urinary tract in 30, and nephrotic syndrome (NS) in 27. The renal pathology in 39 children with CGN or NS was focal glomerular sclerosis in 15, diffuse mesangial GN in 7, IgA GN in 5, membranoproliferative GN in 3, membranous GN in 3, and unclassified in 6. Forms of dialysis initiated were hemodialysis in 91 children, continuous ambulatory peritoneal dialysis (PD) in 66, and intermittent PD in 5. Renal transplantation was performed on 38 children, and the graft and the patient survival rates were 76% and 89%, respectively. The survival rate of our 162 children for a mean follow‐up of 8.1 years was 77%. In conclusion, an integrated program of maintenance dialysis and transplantation provides a favorable life for children with ESRD.
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