Integrin b4 expression in peripheral-nerve tumors

The alpha 6 beta 4 integrin complex is expressed in epithelial, endothelial and nerve cells. We analyzed the immunohistochemical expression of the beta 4 subunit in normal peripheral nerves, in neurofibromas associated with type 1 neurofibromatosis and in sporadic neurofibrosarcomas. In normal peripheral nerves (4 samples), the beta 4 integrin was diffusely expressed at the level of the perinevrium and at the interface between axons and Schwann cells. In neurofibromas (6 cases), beta 4 was undetectable or markedly decreased relative to normal peripheral nerves. Neurofibrosarcomas (3 cases) were immunohistochemically negative for beta 4 expression. These observations suggest that a down-regulation of the alpha 6 beta 4 integrin is associated with the neoplastic progression of peripheral nerve tumors.     

Expression of vascular endothelial growth-factor in the cyst fluid of human cerebral gliomas

Vascular endothelial growth factor (VEGF) or vascular permeability factor (VPF) has been shown to play a key role in angiogenesis in several solid tumours including human brain neoplasms. Its expression has also been found to be correlated to malignancy in the major class of these tumours, gliomas. Moreover, it has been suggested that cyst fluids (CFs) associated with human gliomas may contain a permeability factor responsible for the formation of brain edema and disruption of the blood-brain barrier generally observed in these tumours. We demonstrate that VEGF is present in low and high grade gliomas of seven patients. We also show that VEGF concentration increases with increasing malignancy of the tumours. Although further cases should be investigated, these results suggest that the amount of CF-VEGF may be of value in the diagnosis of human gliomas.     

滇白珠化学成分的研究(Ⅱ)

从滇白珠Ｇａｎｌｔｈｅｒｉａ ｙｕｎｎａｎｅｎｓｉｓ根的乙酸忆是活性部位分得１０个化合物,经理化性质和波谱分析,它们的结构分别鉴定为阿魏酸（Ⅰ）,氯原酸（Ⅱ）,（＋）－儿茶素（Ⅲ）,原花色素Ａ２,芦丁,槲皮素,水杨酸,香草酸,２,５－二羟基七甲酸和原儿茶酸,其中Ⅳ为杜鹃化科植物中首次报道,其它９个化合物为白珠树属植物中首次分得。     

A comparative proteome analysis of hippocampal tissue from schizophrenic and Alzheimer's disease individuals

The proteins expressed by a genome have been termed the proteome. Comparative proteome analysis of brain tissue offers a novel means to identify biologically significant gene products that underlie psychopathology. In this study we collected post mortem hippocampal tissue from the brains of seven schizophrenic, seven Alzheimer's disease (AD) and seven control individuals. Hippocampal proteomes were visualised by two-dimensional gel electrophoresis of homogenised tissue. A mean of 549 (s.d. 35) proteins were successfully matched between each disease group and the control group. In comparison with the control hippocampal proteome, eight proteins in the schizophrenic hippocampal proteome were found to be decreased and eight increased in concentration, whereas, in the AD hippocampal proteome, 35 proteins were decreased and 73 were increased in concentration (P<0.05). One protein, which was decreased in concentration in both diseases, was characterised as diazepam binding inhibitor (DBI) by N-terminal sequence analysis. DBI can regulate the action of the GABA(A) receptor. Protein changes involved 6% of the assessed AD hippocampal proteome, whereas, in schizophrenia protein changes involved less than 1% of the assessed hippocampal proteome. We conclude that schizophrenia has a subtle neuropathological presentation and comparative proteome analysis is a viable means by which to investigate diseases of the brain at the molecular level.     

The effect of ultra-high molecular weight polyethylene wear debris on MG63 osteosarcoma cells in vitro

BACKGROUND: Focal osteolysis due to ultra-high molecular weight polyethylene wear debris involves effects on both bone resorption and bone formation. METHODS: The response of MG63 osteoblast-like osteosarcoma cells to ultra-high molecular weight polyethylene wear debris isolated by enzymatic digestion of granulomatous tissue obtained from the sites of failed total hip arthroplasties was examined. Scanning electron microscopy, particle-size analysis, and Fourier transform infrared spectroscopy were used to characterize the number, morphology, size distribution, and chemical composition of the particles. Cell response was assessed by adding particles at varying dilutions to confluent cultures and measuring changes in cell proliferation (number of cells and [3H]-thymidine incorporation), osteoblast function (alkaline-phosphatase-specific activity and osteocalcin production), matrix production (collagen production and proteoglycan sulfation), and local cytokine production (prostaglandin-E2 production). RESULTS: The mean size of the particles was 0.60 micrometer, and 95 percent of the particles had a size of less than 1.5 micrometers. The number of particles per gram of tissue ranged from 1.39 to 3.38x10(9). Three of the four batches of particles were endotoxin-free. Exposure of the cells to particles of wear debris significantly increased the number of cells (p<0.05) and the [3H]-thymidine incorporation (p<0.05) in a dose-dependent manner. In contrast, the addition of particles decreased alkaline-phosphatase-specific activity and osteocalcin production. Collagen production and proteoglycan sulfation were also decreased, while prostaglandin-E2 synthesis was increased by the addition of particles. CONCLUSIONS: Ultra-high molecular weight polyethylene particles isolated from human tissue stimulated osteoblast proliferation and prostaglandin-E2 production and inhibited cell differentiation and matrix production. These results indicate that particles of wear debris inhibit cell functions associated with bone formation and that osteoblasts may produce factors in response to wear debris that influence neighboring cells, such as osteoclasts and macrophages. CLINICAL RELEVANCE: Particles of wear debris, especially ultra-high molecular weight polyethylene, have been implicated in the loosening of implants and the development of osteolysis. The present study shows that particles of ultra-high molecular weight polyethylene isolated from human tissue inhibit osteoblast functions associated with bone formation. In addition, particles of wear debris induced osteoblasts to secrete factors capable of influencing neighboring cells, such as osteoclasts and macrophages. These results suggest that osteoblasts may play a role in the cascade of events leading to granuloma formation, osteolysis, and failure of orthopaedic implants.     

Genistein inhibits the regulation of active sodium-potassium transport by dopaminergic agonists in nonpigmented ciliary epithelium.

PURPOSE: To determine whether dopamine receptor stimulation regulates Na,K-ATPase-mediated ion transport in cultured nonpigmented ciliary epithelium (NPE). METHODS: Using a rabbit NPE cell line, active Na-K transport activity was determined by measuring ouabain-sensitive potassium (86Rb) uptake in cell monolayers. Western blot analysis of membrane material obtained from cell homogenates was conducted to examine tyrosine phosphorylation of membrane proteins. RESULTS: Ouabain-sensitive potassium (86Rb) uptake was inhibited in the presence of either dopamine or the D1-selective agonist SKF82958. The response was suppressed by SCH23390, a D1 antagonist, but not by sulpiride, a D2-selective antagonist. Quinpirole, a D2-selective agonist, did not cause inhibition of ouabain-sensitive potassium (86Rb) uptake. Cyclic adenosine monophosphate (cAMP) was detectably increased in SKF82958-treated cells, although the concentration of SKF required to elevate cell cAMP was higher than the concentration needed to inhibit ouabain-sensitive potassium (86Rb) uptake. The protein kinase A inhibitor H89 prevented the 86Rb uptake response to SKF82958. Genistein, an inhibitor of tyrosine kinases, also prevented the 86Rb uptake response to SKF82958. Membrane material isolated from cells exposed to SKF82958 showed an increase in the density of several phosphotyrosine bands. These changes in phosphotyrosine immunoblot density were not observed in material isolated from cells that received either genistein or SCH23390 before SKF82958 treatment. CONCLUSIONS: The results of this study suggest D1 agonists cause a reduction of Na,K-ATPase-mediated ion transport by a mechanism that could involve a tyrosine kinase step.