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41.
Applications of a rat multiple tissue gene expression data set 总被引:4,自引:0,他引:4
Walker JR Su AI Self DW Hogenesch JB Lapp H Maier R Hoyer D Bilbe G 《Genome research》2004,14(4):742-749
With the sequencing and assembly of the rat genome comes the difficult task of assigning functions to genes. Tissue localization of gene expression gives some information about the potential role of a gene in physiology. Various examples of the utility of multiple tissue gene expression data sets are illustrated here. First, we highlight their use in finding genes that might play an important role in a particular tissue on the basis of exclusive expression in that tissue or coexpression with a gene or genes with known function. Second, we show how this data might be used to explain known phenotypic differences between strains. Third, we show how expression patterns of genes in a genomic interval might identify candidate genes in quantitative trait loci (QTL) mapping studies. Lastly, we show how multiple tissue and species data can help researchers prioritize follow up studies to microarray experiments. All of these applications of multiple tissue gene expression data sets will play a role in functionally annotating the rat genome. 相似文献
42.
Mast cell tryptase and proteinase-activated receptor 2 induce hyperexcitability of guinea-pig submucosal neurons 总被引:5,自引:2,他引:5
David E. Reed Carlos Barajas-Lopez Graeme Cottrell Sara Velazquez-Rocha Olivier Dery Eileen F. Grady Nigel W. Bunnett Stephen J. Vanner 《The Journal of physiology》2003,547(2):531-542
Mast cells that are in close proximity to autonomic and enteric nerves release several mediators that cause neuronal hyperexcitability. This study examined whether mast cell tryptase evokes acute and long-term hyperexcitability in submucosal neurons from the guinea-pig ileum by activating proteinase-activated receptor 2 (PAR2) on these neurons. We detected the expression of PAR2 in the submucosal plexus using RT-PCR. Most submucosal neurons displayed PAR2 immunoreactivity, including those colocalizing VIP. Brief (minutes) application of selective PAR2 agonists, including trypsin, the activating peptide SL-NH2 and mast cell tryptase, evoked depolarizations of the submucosal neurons, as measured with intracellular recording techniques. The membrane potential returned to resting values following washout of agonists, but most neurons were hyperexcitable for the duration of recordings (> 30 min–hours) and exhibited an increased input resistance and amplitude of fast EPSPs. Trypsin, in the presence of soybean trypsin inhibitor, and the reverse sequence of the activating peptide (LR-NH2 ) had no effect on neuronal membrane potential or long-term excitability. Degranulation of mast cells in the presence of antagonists of established excitatory mast cell mediators (histamine, 5-HT, prostaglandins) also caused depolarization, and following washout of antigen, long-term excitation was observed. Mast cell degranulation resulted in the release of proteases, which desensitized neurons to other agonists of PAR2. Our results suggest that proteases from degranulated mast cells cleave PAR2 on submucosal neurons to cause acute and long-term hyperexcitability. This signalling pathway between immune cells and neurons is a previously unrecognized mechanism that could contribute to chronic alterations in visceral function. 相似文献
43.
The reliability of prealbumin as a diagnostic marker was studied in 60 cases of bronchopulmonary carcinoid tumours. There were differences in the incidence of positivity between typical and atypical carcinoids (well differentiated neuroendocrine carcinomas). Seventy five per cent of the carcinoid tumours were positive for prealbumin; (86.7% typical and 63.3% atypical carcinoids). In 15 cases, which were Grimelius negative, 10 were prealbumin positive. Only 8.3% carcinoids were negative with both prealbumin and Grimelius stains. Ten squamous, 10 adeno- and 10 small cell carcinomas showed only occasional scattered prealbumin positive cells. It is concluded that prealbumin is a useful marker for bronchopulmonary carcinoid tumours. It is cheap, readily available, and should be considered part of routine diagnostic procedures for the diagnosis of carcinoid tumours. 相似文献
44.
Moyle GJ DeJesus E Cahn P Castillo SA Zhao H Gordon DN Craig C Scott TR;Ziagen Once-Daily in Antiretroviral Combination Therapy 《Journal of acquired immune deficiency syndromes (1999)》2005,38(4):417-425
The long intracellular half-life of abacavir (ABC) supports its once-daily use, and this would be expected to simplify treatment if ABC could be given as part of a complete once-daily regimen. A randomized double-blind clinical trial compared the efficacy and safety of 600 mg of ABC administered once daily (n = 384) versus 300 mg of ABC administered twice daily (n = 386) in combination with 300 mg of lamivudine (3TC) and 600 mg of efavirenz (EFV) administered once daily in antiretroviral-naive patients over 48 weeks. The baseline median plasma HIV-1 RNA level was 4.89 log10 copies/mL (44% with viral load >100,000 copies/mL), and the median CD4 cell count was 262 cells/mm. ABC administered once daily was non-inferior to the twice-daily regimen, with 66% and 68% of patients in these respective treatment arms achieving a confirmed plasma HIV-1 RNA level <50 copies/mL (95% confidence interval: -8.4%, 4.9%). The ABC once-daily and twice-daily regimens were similar with respect to infrequency of virologic failure (10% vs. 8%), emergence of resistance mutations, CD4 cell increases from baseline (median, 188 vs. 200 cells/mm), safety profile, and incidence of ABC-related hypersensitivity reactions (9% vs. 7%). ABC administered once daily in combination with 3TC and EFV administered once daily was non-inferior to the ABC twice-daily dosing schedule when combined with 3TC and EFV over 48 weeks. 相似文献
45.
DNA end-independent activation of DNA-PK mediated via association with the DNA-binding protein C1D
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Ugur Yavuzer Graeme C.M. Smith Tonya Bliss Dieter Werner Stephen P. Jackson 《Genes & development》1998,12(14):2188-2199
DNA-dependent protein kinase (DNA-PK), which is involved in DNA double-strand break repair and V(D)J recombination, is comprised of a DNA-targeting component termed Ku and an ~465-kD catalytic subunit, DNA-PKcs. Although DNA-PK phosphorylates proteins in the presence of DSBs or other discontinuities in the DNA double helix in vitro, the possibility exists that it is also activated in other circumstances via its association with additional proteins. Here, through use of the yeast two-hybrid screen, we discover that the recently identified high affinity DNA binding protein C1D interacts with the putative leucine zipper region of DNA-PKcs. Furthermore, we show that C1D can interact with DNA-PK in mammalian cells and that C1D is a very effective DNA-PK substrate in vitro. Finally, we establish that C1D directs the activation of DNA-PK in a manner that does not require DNA termini. Therefore, these studies provide a function for C1D and suggest novel mechanisms for DNA-PK activation in vivo. 相似文献
46.
47.
Pastorino L Cusano R Bruno W Lantieri F Origone P Barile M Gliori S Shepherd GA Sturm RA Bianchi-Scarra G Scarra GB 《Human mutation》2004,24(1):103
Several variant forms of the melanocortin-1 receptor gene (MC1R) have been associated with red hair, fair skin and an increased risk for melanoma. Their involvement in melanoma susceptibility is apparently linked both to skin sensitivity and to non-pigmentary pathways. We investigated the frequency of the MC1R variants in the Italian region of Liguria, where the occurrence and penetrance of melanoma are low and primary susceptibility is characterized by prevalence of the CDKN2A c.301G>T [p.G101W] founder mutation. Additionally, we attempted to establish the frequency of the red hair/fair skin phenotype in our region. As predicted by anecdotal evidence, the frequency of red hair/phototype I was very low (0.7%). Screening of 17 red-haired individuals and their red-haired relatives, 207 controls and 214 melanoma patients unselected for hair color but all of Ligurian descent, led to the detection of 8 novel substitutions (c.133T>C [p.F45L], c.248C>T [p.S83L], c.332C>T [p. A111V], c.479G>A [p.R160Q], c.637C>T [p.R213W], c.793G>A [p. V265I], c.923C>T [p. T308M], c.943T>C [p.C315R]), 1 novel deletion (c.520_523delGTC [p.V174del]) and 3 novel synonymous variants (c.366G>C [p. V122V], c.684G>A [p. Q228Q], c.726C>T [p.T241T]). Preliminary genotype/phenotype correlation seems to indicate that other genes involved in the regulation of human pigmentation may mask the recessive action of high-penetrance MC1R alleles, thus determining the low frequency of at-risk phototypes and of incidence and/or penetrance of melanoma in Liguria. 相似文献
48.
Mazarakis ND Azzouz M Rohll JB Ellard FM Wilkes FJ Olsen AL Carter EE Barber RD Baban DF Kingsman SM Kingsman AJ O'Malley K Mitrophanous KA 《Human molecular genetics》2001,10(19):2109-2121
In this report it is demonstrated for the first time that rabies-G envelope of the rabies virus is sufficient to confer retrograde axonal transport to a heterologous virus/vector. After delivery of rabies-G pseudotyped equine infectious anaemia virus (EIAV) based vectors encoding a marker gene to the rat striatum, neurons in regions distal from but projecting to the injection site, such as the dopaminergic neurons of the substantia nigra pars compacta, become transduced. This retrograde transport to appropriate distal neurons was also demonstrated after delivery to substantia nigra, hippocampus and spinal cord and did not occur when vesicular stomatitis virus glycoprotein (VSV-G) pseudotyped vectors were delivered to these sites. In addition, peripheral administration of rabies-G pseudotyped vectors to the rat gastrocnemius muscle leads to gene transfer in motoneurons of lumbar spinal cord. In contrast the same vector pseudotyped with VSV-G transduced muscle cells surrounding the injection site, but did not result in expression in any cells in the spinal cord. Long-term expression was observed after gene transfer in the nervous system and a minimal immune response which, together with the possibility of non-invasive administration, greatly extends the utility of lentiviral vectors for gene therapy of human neurological disease. 相似文献
49.
Hormone therapy and affect 总被引:2,自引:0,他引:2
This study investigated the influence of hormone therapy on affect in a double blind crossover trial. The sample consisted of 49 women who had previously undergone hysterectomy and bilateral oophorectomy. Therapy consisted of 3 mth each of ethinyl oestradiol — 50 μg/day, levonorgestrel — 250 μg/day, “Nordial” — a combination of these two substances, and placebo. Affect was measured by the Hamilton Depression Rating Scale, verbal reports by women and self-ratings on visual analogue scales. Ethinyl oestradiol was found to have a beneficial influence on aspects of affect such as Hamilton scores, anxiety, irritability and insomnia.
The influence of hormones on Hamilton scores could be partly but not fully explained by the alleviation of hot flushes. Norgestrel showed less favourable changes initially but these tended to diminish by the third therapy month. Most of the women studied were not clinically depressed. Anxiety symptoms were the major features exhibited in the group of women investigated. The results of this study suggest that visual analogue rating scales are of questionable validity in assessing affect in patients without any appreciable psychiatric morbidity. 相似文献
50.
Moyle GJ Daar ES Gertner JM Kotler DP Melchior JC O'brien F Svanberg E;Serono Study Team 《Journal of acquired immune deficiency syndromes (1999)》2004,35(4):367-375
HIV-associated wasting is defined as > or = 10% involuntary weight loss and includes declines in both lean and fat mass. This large (757 subjects), randomized, double-blind, placebo-controlled trial investigated the efficacy, safety, and tolerability of recombinant human growth hormone (rhGH) in 2 doses-0.1 mg/kg up to a maximum of 6 mg daily (DD) or alternate days (AD)-in the treatment of wasting and weight loss in highly active antiretroviral therapy (HAART)-treated HIV-infected subjects. The evaluable population for ergometry comprised 555 subjects, 87.6% of whom were receiving HAART. At 12 weeks, median maximum work output increased by 2.4 and 2.6 kJ in the AD and DD groups, respectively. The median treatment difference was 2.9 kJ for DD vs. placebo (P < 0.0001). Body weight increased by 2.2 and 2.9 kg in the AD and DD groups, respectively. Corresponding median treatment differences vs. placebo were 1.5 and 2.2 kg (P < 0.0001). Lean body mass (LBM), by bioelectric impedance spectroscopy, increased by 3.3 and 5.2 kg, respectively (P < 0.0001 vs. placebo; P = 0.0173 DD vs. AD), and fat mass, predominately truncal, decreased. Quality of life (QoL) improved significantly in both rhGH groups. Fluid-retention adverse effects and hyperglycemia were more common in the DD than in the AD group. No significant changes in HIV viral load or CD4 cell count occurred. In conclusion, over the 12-week course of therapy, rhGH, 0.1 mg/kg DD, was superior to placebo in improving physical function, body weight, body composition, and QoL and was superior to AD dosing in restoring LBM. 相似文献