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101.
Saireudee Chaturantabut Arkadi Shwartz Kimberley J. Evason Andrew G. Cox Kyle Labella Arnout G. Schepers Song Yang Mariana Acuña Yariv Houvras Liliana Mancio-Silva Shannon Romano Daniel A. Gorelick David E. Cohen Leonard I. Zon Sangeeta N. Bhatia Trista E. North Wolfram Goessling 《Gastroenterology》2019,156(6):1788-1804.e13
102.
Platelet Derived Growth Factor (PDGF) autocrine components in human tumor cell lines 总被引:1,自引:0,他引:1
Griffith R. Harsh Mark T. Keating Jaime A. Escobedo Lewis T. Williams 《Journal of neuro-oncology》1990,8(1):1-12
Tumor cells may stimulate their own proliferation through an autocrine mechanism by simultaneously producing growth factors and growth factor receptors. We now report that numerous human tumor-derived cell lines simultaneously express the genes for platelet-derived growth factor (PDGF) A and B chains and the PDGF receptor (PDGF-R). Measurement of mRNA transcribed from these genes showed that among 16 malignant glioma cell lines tested, 15 expressed the PDGF A gene, 12 expressed the PDGF B gene, and 13 expressed the PDGF-R gene. Of three osteosarcoma lines, three expressed PDGF A, two expressed PDGF B, and three expressed PDGF-R. For eight malignant melanoma lines, seven expressed PDGF A, five expressed PDGF B, and three expressed PDGF-R genes. Thus, 13 of 16 malignant glioma, 3 of 3 osteosarcomas, and 3 of 8 malignant melanoma cell lines expressed the PDGF receptor gene and either or both PDGF genes. Five cell lines were tested for production of biologically active PDGF and PDGF receptor protein. Media conditioned by each of the five cell lines induced tyrosine phosphorylation of a protein identical in size to the PDGF receptor. These five cell lines also produced PDGF receptor protein as measured by Western blot analysis or metabolic labeling and immunoprecipitation using PDGF-R antibodies. The PDGF receptors of these cell lines were activated by human platelet PDGF or by recombinant AA or BB homodimers. Intracellular interaction of these receptors with the growth factor simultaneously produced may provide continuous stimulation to the proliferation of these cells. 相似文献
103.
Serotonin receptors incorporated in the membrane of Xenopus oocytes injected with mRNA extracted from the rat brain was investigated b by intracellular recording. Serotonin elicited the membrane depolarization accompanied with membrane potential fluctuations. This serotonin action was suppressed by serotonin antagonists such as methysergide, cyproheptadine and ketanserin. Dibutyryl cyclic AMP and papaverine depolarized the membrane as seen in applying serotonin. These observations indicate that serotonin actions might involve the cAMP system. 相似文献
104.
外阴阴道假丝酵母菌病患者阴道局部甘露糖结合凝集素mRNA水平的测定 总被引:1,自引:0,他引:1
目的:初步探讨甘露糖结合凝集素(MBL)在外阴阴道念珠菌病(VVC)和复发性外阴阴道念珠菌病(RVVC)发病过程中的免疫机制。方法:选取2006年1月~2007年7月健康体检的女性、VVC患者、RVVC患者各20例,采集阴道灌洗液,半定量RT-PCR测定MBL-mRNA表达情况。结果:阴道局部MBL-mRNA的表达VVC患者显著高于正常人群,而RVVC患者显著低于正常人群。结论:VVC患者阴道局部MBL-mRNA高表达说明MBL参与了局部免疫反应,其在免疫防御中发挥了重要作用,而阴道局部MBL-mRNA的低表达可能和RVVC反复发作不易治疗有关,提示有必要对MBL水平低下者进行MBL临床治疗的研究。 相似文献
105.
Hye-Sook Chang Miyan Ko Mayumi Ishizuka Shoichi Fujita Akira Yabuki Mohammad Alamgir Hossain Osamu Yamato 《Nutrition Research》2010
There is evidence that onions and garlic protect against cancer in humans. It has been suggested that this effect is partly due to the organosulfur compounds in Allium vegetables and that these substances act through induction of phase II detoxification enzymes. Here, we hypothesized that alk(en)yl thiosulfates, sodium n-propyl thiosulfate (NPTS), and sodium 2-propenyl thiosulfate (2PTS), which were identified in onions and garlic, respectively, may induce phase II enzymes. Therefore, rat hepatoma cells (H4IIE) were cultured with 1 to 100 μmol/L of NPTS or 2PTS for 48 hours at 37°C; and the activities and messenger RNA (mRNA) expression levels of phase II enzymes in H4IIE cells were investigated. The effects of diallyl trisulfide and tert-butylhydroquinone, known as phase II inducers, were also examined as positive controls and compared with the responses of NPTS and 2PTS. Quinone reductase (QR) activity and mRNA expression levels of QR and epoxide hydrolase 1 were significantly increased by 2PTS (P < .05-.005). In particular, QR activity was increased at a relatively low concentration of 2PTS (10 μmol/L). However, glutathione S-transferase activity and mRNA expression levels of glutathione S-transferase A5 and uridine diphosphate glucuronosyl transferase 1A1 were not changed by 2PTS. In contrast, NPTS did not affect the activities and mRNA expression levels of these phase II enzymes. These results show that 2PTS can induce phase II enzymes, and its inductive effect is comparable or superior to that of diallyl trisulfide and tert-butylhydroquinone. 相似文献
106.
Sayamwong E. Hammack Ji-Dong Guo Rimi Hazra Joanna Dabrowska Karyn M. Myers Donald G. Rainnie 《Progress in neuro-psychopharmacology & biological psychiatry》2009
Substantial evidence has suggested that the activity of the bed nucleus of the stria terminalis (BNST) mediates many forms of anxiety-like behavior in human and non-human animals. These data have led many investigators to suggest that abnormal processing within this nucleus may underlie anxiety disorders in humans, and effective anxiety treatments may restore normal BNST functioning. Currently some of the most effective treatments for anxiety disorders are drugs that modulate serotonin (5-HT) systems, and several decades of research have suggested that the activation of 5-HT can modulate anxiety-like behavior. Despite these facts, relatively few studies have examined how activity within the BNST is modulated by 5-HT. Here we review our own investigations using in vitro whole-cell patch-clamp electrophysiological methods on brain sections containing the BNST to determine the response of BNST neurons to exogenous 5-HT application. Our data suggest that the response of BNST neurons to 5-HT is complex, displaying both inhibitory and excitatory components, which are mediated by 5-HT1A, 5-HT2A, 5-HT2C and 5-HT7 receptors. Moreover, we have shown that the selective activation of the inhibitory response to 5-HT reduces anxiety-like behavior, and we describe data suggesting that the activation of the excitatory response to 5-HT may be anxiogenic. We propose that in the normal state, the function of 5-HT is to dampen activity within the BNST (and consequent anxiety-like behavior) during exposure to threatening stimuli; however, we suggest that changes in the balance of the function of BNST 5-HT receptor subtypes could alter the response of BNST neurons to favor excitation and produce a pathological state of increased anxiety. 相似文献
107.
The ability to isolate intact RNAs from postmortem human brain permits analysis of gene expression and may help uncover the nature of the molecular lesions in neurological diseases. Starting with poly(A) RNA from postmortem brain of neurologically normal patients, we have constructed two complementary DNA libraries in the plasmid vector pBR322. Each of these libraries contains 2-3 X 10(4) recombinants. One library represents RNA species from the cerebellar cortex, the other from the neostriatum. Using differential colony hybridization, we identified more than 100 relatively abundant RNA species that appeared to be expressed in brain but not in liver. We then used 16 of these clones to analyze brain and liver RNAs by RNA blot hybridization. Thirteen of the 16 clones hybridized to RNAs of both liver and brain. One clone hybridized only to brain RNA, while seven hybridized to RNA species that were present at higher concentrations in brain than in liver. Eleven of the 16 clones hybridized to more than one species of RNA. None of the RNA species examined by RNA blot hybridization was limited to a single brain region, though seven of the cDNA clones hybridized to RNAs that were present at different concentrations in different regions. We have also examined the regional distribution of the RNA encoding glutamic acid decarboxylase, which catalyzes the production of gamma-aminobutyric acid (GABA). GAD RNA showed differential expression among brain regions and was not detectable in liver or kidney. Our data support a model of gene regulation that is based on cell identity, rather than regional specificity. 相似文献
108.
Bcl-2 mRNA和Bax mRNA在增生性瘢痕中的表达及意义 总被引:1,自引:0,他引:1
【目的】观察Bcl-2 mRNA和Bax mRNA在增生性疲痕和正常皮肤组织内的表达特征及其对增生性瘢痕形成的影响。【方法】收集20例增生性疲痕和20例正常皮肤组织,常规制作石蜡包埋切片,Bcl-2 mRNA和Bax mRNA染色方法为分子原位杂交染色法。【结果】Bcl-2 mRNA和Bax mRNA杂交信号阳性产物定位于胞浆。增生性疲痕Bcl-2 mRNA表达阳性率及其评分明显高于正常皮肤(P〈0.01);增生性瘢痕Bax mRNA表达阳性率及其评分与正常皮肤无明显差异(P〉0.05)。【结论】Bcl-2基因表达增强可能是瘢痕中细胞凋亡减少,形成增生性瘢痕的机制之一。 相似文献
109.
Sánchez-Campos S Alvarez M Culebras JM Gonzalez-Gallego J Tuñón MJ 《The Journal of laboratory and clinical medicine》2004,144(4):215-222
In this study we sought to determine whether molecular mechanisms involved in the pathogenesis of fulminant hepatic failure are present in rabbits experimentally infected with rabbit hemorrhagic disease virus (RHDV). The activities of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, as well as bilirubin concentration, were found to be significantly increased 36 hours after infection. Infected animals also demonstrated significant decreases in factor VII activity, in the Fischer index, and in the deterioration of prothrombin time. The concentration of reduced glutathione was significantly decreased 36 hours after infection, and we noted a marked increase in the ratio of oxidized to reduced glutathione. Infected animals showed progressive decreases in liver activity of the antioxidant enzyme superoxide dismutase. Expression of hepatocyte growth factor and c-met was found to be progressively reduced from 24 hours after infection, during which time we detected no modification in messenger RNA (mRNA) levels of transforming growth factor (TGF)-alpha. TFG-beta 1 was overexpressed 24 and 36 hours after infection, and 36 hours after infection we detected a significant increase in TNF-alpha mRNA levels. Experimental RHDV infection also induced marked activation of nuclear factor-kappaB and a significant increase in inducible nitric oxide synthase mRNA levels from 24 hours after infection. Data obtained from this animal model support its usefulness in the investigation of potential novel therapeutical modalities aimed at neutralizing reactive oxygen species and hepatocyte growth inhibitors or enhancing hepatocyte responsiveness to mitogens. 相似文献
110.
Svanberg E Ohlsson C Kimball SR Lundholm K 《European journal of clinical investigation》2000,30(5):438-446
BACKGROUND: The aim of this study was to evaluate the effect of insulin like growth factor-I (rhIGF-I) in complex with binding protein 3 (IGFBP 3) compared to the effect of free IGF-I on muscle protein biosynthesis in undernourished animals. METHODS: Three groups of female Sprague-Dawley rats (200 g) were initially semi-starved for 3 days and then treated with saline (controls), rhIGF-I (1 microg g-1) or equimolar amounts of rhIGF-I/rhIGFBP-3 complex (5 microg g-1) i.v. twice daily for 3 days during continuous semistarvation. Protein metabolism in hind limb skeletal muscle was studied by incorporation of L-[14C-U]phenylalanine into proteins, western blot determination of translation initiation factors involved in the binding of the 40S ribosomal subunit to mRNA, and quantification of mRNA content for IGF-I, IGF-IR and GH-R. Plasma measurements of insulin, IGF-I and amino acids were also performed. RESULTS: rhIGF-I/rhIGFBP-3, but not rhIGF-I alone, stimulated protein synthesis by 177 +/- 26% (P = 0.05) in semi-starved rats. This stimulation was associated with dissociation of the 4E-BP1. eIF-4E complex, implicating increased binding of the 40S ribosomal subunit to mRNA, and hence increased initiation of protein synthesis in these animals. Muscle content of IGF-I mRNA was reduced in semi-starved animals, whereas IGF-I receptor mRNA was unaltered despite food restriction. Plasma concentration of IGF-I was 20% (P = 0.05) higher in rhIGF-I/rhIGFBP-3 treated animals as compared to rats treated with saline or free IGF-I. Plasma concentrations of amino acids were increased in rhIGF-I/rhIGFBP-3 treated animals (P = 0.05 vs. semi-starved controls). CONCLUSION: rhIGF-I/rhIGFBP-3 (SomatoKine) was a significant stimulator of muscle protein synthesis in chronically semi-starved animals whereas IGF-I alone failed to increase protein synthesis during the same experimental conditions. This stimulation was because of increased initiation of translation, likely induced by more physiologic concentrations/kinetics of plasma IGF-I and amino acids following rhIGF-I/rhIGFBP-3 treatment, compared to IGF-I in its free form. 相似文献