Significance of glomerular activation of the alternative pathway and lectin pathway in lupus nephritis.

The objective of the present study was to elucidate the association between glomerular complement depositions belonging to the alternative (AP) and lectin (LP) pathways, and clinical findings of lupus nephritis (LN). Immunofluorescence (IF) was performed on 17 LN patients using antibodies against factor B, factor H, properdin, mannose-binding lectin (MBL) and L-ficolin. Compared with factor B/factor H negative patients (n = 9), positive patients (n = 8) showed longer duration of LN (p < 0.05) and more severe interstitial fibrosis (p < 0.05). Eleven patients had properdin deposition in glomeruli, and in three of them, with a duration of LN of less than 1 month, factor B was undetectable. Compared with properdin negative patients (n = 6), positive patients (n = 11) showed significantly higher urinary protein excretion (p < 0.01). MBL/L-ficolin positive patients (n = 11) also had significantly higher urinary protein excretion (p < 0.05) compared with negative patients (n = 6). An independent association was found between glomerular deposition of properdin and that of MBL/L-ficolin (p < 0.01) in addition to factor B/factor H. Traces of glomerular activation of AP and LP reflected the clinical status of LN. It appears that glomerular deposition of each complement component, especially properdin, may be an index of the histological activity of LN.

Improvement of peritoneal calcification after parathyroidectomy in a peritoneal dialysis patient.

Peritoneal calcification is one of the complications of peritoneal dialysis (PD). It can become serious, leading to severe abdominal pain and even death. Possible mediators of peritoneal calcification in PD patients are assumed to include acetate buffer, overdosage of vitamin D, repeated peritonitis, hypertonic dialysate, calciphylaxis and secondary hyperparathyroidism (SHPT). However, the mechanism and treatment of peritoneal calcification are controversial. Few reports have appeared on improvement of peritoneal calcification after parathyroidectomy (PTX) for SHPT of long duration. We report herein the case of a 48-year-old man on dialysis for 17 years including PD for 14 years. In 1989, he was admitted to hospital because of end-stage renal disease (ESRD), and started treatment with PD. Abdominal computed tomography (CT) first showed peritoneal calcification in August 2002. Peritoneal calcification did not improve despite conventional treatment including discontinuation of PD, control of calcium phosphate product to less than 55 mg2/dl2, removal of the peritoneal catheter and empirical prednisolone (PSL) usage. The intact parathyroid hormone (i-PTH) level was increased over 1,000 pg/ml and extra-osseous calcification occurred. Total PTX was performed in November 2004. Postoperatively, the i-PTH level decreased immediately and calcium phosphate product was maintained in the reference range. Abdominal CT after PTX showed improvement of peritoneal calcification in September 2005. It appeared that PTX could be used to treat patients with persistent peritoneal calcification not responding to conventional treatment. It was postulated that SHPT might play a crucial role in accelerating peritoneal calcification in PD patients.

The different effects of endocrine-disrupting chemicals on estrogen receptor-mediated transcription through interaction with coactivator TRAP220 in uterine tissue.

An endocrine-disrupting chemical (EDC) can alter endocrine functions through a variety of mechanisms, including nuclear receptor-mediated changes in protein synthesis, interference with membrane receptor binding, steroidogenesis or synthesis of other hormones. Although major chemicals have been shown to disrupt estrogenic actions mainly through their binding to estrogen receptor (ER) or androgen receptor, it is not clear how EDCs affect endocrine functions in vivo. We present evidence that the EDCs bisphenol A and phthalate activate ER-mediated transcription through interaction with TRAP220. Moreover, bisphenol A had positive effects on the interaction between ER-beta and TRAP220 and on the expression of ER-beta and TRAP220 compared with phthalate and estradiol in uterine tIssue. These data suggested that some EDCs might alter endocrine function through the change of the receptor and coactivator levels in uterine tIssue and through the different effect on the interaction between ERs and coactivator TRAP220.

The expression of pregnane X receptor and its target gene, cytochrome P450 3A1, in perinatal mouse.

Recently, pregnane X receptor (PXR) has been described to mediate the genomic effects of several steroid hormones, such as progesterone (P), glucocorticoid (Dex), pregnenolone (Preg), and xenobiotics through the cytochrome P-450 3A gene family (CYP3A), which are monooxygenases, responsible for the oxidative metabolism of some endogenous substrates and xenobiotics. In the present study, we used a transient transfection reporter gene expression assay of COS-7 cells to demonstrate that P, Dex and Preg significantly stimulate PXR-mediated transcription at relatively high concentration comparable with that of progesterone near term pregnancy. In yeast two-hybrid protein interaction assay, PXR interacted with nuclear receptor coactivator proteins, SRC1, RIP140, and SUG1 in a ligand-dependent manner. The expression of PXR mRNA was observed in the liver, intestine, uterus, ovary and placenta. The expressions of PXR mRNA in the liver and ovary increased towards term about fifty-fold compared with that of non-pregnancy and decreased postpartum. Its expression in the placenta was not drastically changed towards term. CYP3A, a target gene of PXR, was also expressed in the liver, ovary, and placenta. The expressions of CYP3A mRNA as well as PXR in the liver and ovary increased about 20-fold during prenatal period. These data suggest that PXR may play certain roles in perinatal period, possibly in the protection of the feto-maternal system from the toxic effect of endogenous steroids and foreign substrates.