メサンギウム サイボウ ゾウショク ニカンスル アラタナ セイギョ インシ ト ビョウヘン ヨクシ ニカンスル ケンキュウ

Mesangial proliferation is a common feature of many glomerular diseases, therefore, understanding the regulatory mechanism is important for the treatment of glomerular diseases. The present study showed growth arrest gene-6 (Gas6) is a new autocrine growth factor of mesangial cells and warfarin inhibited mesangial proliferation by inhibiting γ-carboxylation of Gas 6 in vitro and in vivo. We also found vitamin D anlog (22-oxa-calcitriol) is a new growth regulator for mesangial cells in vivo. These results indicate that these compounds have considerable potential for use as therapeutic strategy in the treatment of progressive glomerular disease

The contribution of mesangial cell proliferation to progressive glomerular injury

Mesangial cell proliferation is a general characteristic of a variety of glomerular diseases. Therefore, an understanding of the regulatory mechanism is important for treatment of glomerular diseases. The present review shows that the growth arrest gene 6 (Gas 6) is a new autocrine growth factor of mesangial cells and that warfarin inhibits mesangial cell proliferation by inhibiting the γ-carboxylation of Gas 6 in vitro and in vivo. The present findings also show that a vitamin D analog (22-oxa-calcitriol) is a new growth regulator of mesangial cells in vitro and in vivo. These findings indicate that these compounds have considerable potential for therapeutic use in the treatment of progressive glomerular disease

The determination of glial fibrillary acidic protein for the diagnosis and histogenetic study of central nervous system tumors: a study of 152 cases.

Glial fibrillary acidic protein (GFAP) was purified from human spinal cord and cerebral white matter. GFAP was localized by an immuno-peroxidase method in normal adult and fetal human brains, rat brains, and 152 central nervous system (CNS) tumors. GFAP was found in reactive and normal astrocytes, immature cells of fetal brain at the 18th to 21st gestational weeks, and normal rat astrocytes. This GFAP staining was quite specific for glial tumors, including astrocytomas, glioblastomas, astroblastomas, and ependymomas. GFAP-positive cells were also found in oligodendrogliomas and choroid plexus papillomas, and they were interpreted as being astroglial or ependymal differentiations. Stromal cells in cerebellar hemangioblastomas were negative. However, engulfed astrocytes were found at the periphery of such tumors and often adjacent to the proliferate blood vessels. In meningiomas, neurinomas, metastatic carcinomas, pituitary adenomas and other non-glial tumors, GFAP-positive cells were not identified.</p

シンキ サイボウ エネルギー タイシャ スクリーニング ニ モトズイタ キュウセイ ジンショウガイ ヨボウヤク チリョウヤク ノ タンサク ト カイハツ

Acute kidney injury（AKI）is a big clinical problem. In addition to high mortality rate, AKI is a potent risk factor of end-stage kidney disease. Ischemia reperfusion injury（IRI）is the leading cause of AKI and we have no specific treatment options to treat AKI. Shifting energy metabolism from mitochondrial respiration to glycolysis may offer a novel therapy against ischemic organ injury. Based on this theory, Meclizine, first-generation antihistamine used for motion sickness and vertigo, was identified in a novel chemical screen. Kidney tubular injury after ischemia reperfusion was significantly decreased in meclizine treated mice compared with the vehicle treated mice（１００mg/kg of meclizine, １７ hours prior to ischemia）. Meclizine treated kidney showed reduced inflammation, oxidative stress and mitochondrial fragmentation after IRI. Meclizine pretreatment reduced mitochondrial oxygen consumption. Reduced cell death and cytochrome c release was found in kidney tubular epithelial cells. Metabolic profiling revealed that Meclizine caused rapid accumulation of cellular phosphoethanolamine（PEtn）. PEtn inhibits mitochondrial respiration and is an intermediate in phosphatidylethanolamine biosynthesis pathway（Kennedy pathway）. In conclusion, Meclizine, or a derivative, is a candidate drug to minimize AKI risk and Kennedy pathway can be a novel therapeutic target for ischiemic kidney injury

Advanced glycation end products modulate transcriptional regulation in mesangial cells

Advanced glycation end products modulate transcriptional regulation in mesangial cells. Advanced glycation end products (AGEs) stimulate synthesis of extracellular matrix (ECM) in a receptor-mediated manner on mesangial cells. In the present study, we examined the transcriptional regulation of the gene for type IV collagen [(IV)collagen], which is one of the major components of mesangial sclerosis, after stimulation of AGEs on mesangial cells. The methylation pattern of the promoter/enhancer region of (IV)collagen gene was similar in AGE-treated and control cells. AGEs significantly increased the transcriptional activity of the (IV)collagen gene, as measured by transient transaction assays using the reporter gene construct containing (IV)collagen promoter/enhancer and the chloramphenicol acetyltransferase gene. AGEs also increased smooth muscle α-actin mRNA levels as well as its transcriptional activity. Nuclear factor binding of the promoter of (IV)collagen gene was stimulated by AGEs. Furthermore, AGEs dramatically decreased the mRNA levels of (IV)collagen promoter binding protein (MSW), a larger subunit of DNA replication complex, AP1. These results suggest that AGEs increase expression of (IV)collagen gene by modulating the levels of promoter binding proteins. These transcriptional events may play a critical role in ECM accumulation in response to AGEs

Low serum sodium concentration is a prognostic factor related to current blood glucose level in stable hemodialysis patients : an observational study

Background: A lot of risk factors for mortality have been proposed in hemodialysis patients. However, most of the findings were derived from the analyses using all of the hemodialysis patients. What we really want to know is the prognostic factor in stable hemodialysis patients who have good activities of daily living, because it is difficult to estimate their prognosis by physical appearance. Methods: This is a 7-year observational study. The study involved registering 631 patients who had undergone hemodialysis for more than 1 year at enrollment and were still alive more than 1 year after it. Demographic and clinical data were collected to analyze the relationship with mortality. Moreover, the patients were age-stratified to investigate age-dependent prognostic factors. Results: Low serum sodium concentration is an independent risk factor for all-cause and cardiovascular mortality common to a wide range of ages in stable hemodialysis patients. Causes of hyponatremia included the predialysis blood glucose level as well as the variables related to nutrition, inflammation, and fluid overload. Conclusions: Low serum sodium concentration is a significant prognostic factor in stable hemodialysis patients. Low serum sodium concentration can be a clue to finding current poor glucose control in stable hemodialysis patients. Predialysis blood glucose level is one of the representative factors correlated with serum sodium concentration