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131.
132.
Background
Press releases are a popular vehicle to disseminate health information to the lay media. While the quality of press releases issued by scientific conferences and medical journals has been questioned, no efforts to assess pharmaceutical industry press releases have been made. Therefore, we sought to systematically examine pharmaceutical company press releases about original research for measures of quality.Methodolgy/Principal Findings
Press releases issued by the ten top selling, international pharmaceutical companies in the year 2005 were selected for evaluation. A total of 1028 electronic press releases were issued and 235 were based on original research. More than half (59%) reported results presented at a scientific meeting. Twenty-one percent of releases were not explicit about the source of original data. While harms or adverse events were commonly cited (76%), study limitations were rarely noted (6%). Almost one-third (29%) of releases did not quantify study results. Studies presented in abstract form were subsequently published within at least 20 months in 53% of cases.Conclusions
Pharmaceutical company press releases frequently report basic study details. However, readers should be cautioned by the preliminary nature of the data and lack of identified limitations. Methods to improve the reporting and interpretation of drug company press releases are desirable to prevent misleading media coverage. 相似文献133.
Experimental evidence for a direct cytotoxicity of Loxosceles intermedia (brown spider) venom in renal tissue. 总被引:3,自引:0,他引:3
Melissa N Luciano Paulo H da Silva Olga M Chaim Vera Lucia P dos Santos Célia Regina C Franco Maria Fernanda S Soares Silvio M Zanata Oldemir C Mangili Waldemiro Gremski Silvio S Veiga 《The journal of histochemistry and cytochemistry》2004,52(4):455-467
Brown spider (Loxosceles genus) venom causes necrotic lesions often accompanied by fever, hemolysis, thrombocytopenia, and acute renal failure. Using mice exposed to Loxosceles intermedia venom, we aimed to show whether the venom directly induces renal damage. The experimental groups were composed of 50 mice as controls and 50 mice that received the venom. Light microscopic analysis of renal biopsy specimens showed alterations including hyalinization of proximal and distal tubules, erythrocytes in Bowman's space, glomerular collapse, tubule epithelial cell blebs and vacuoles, interstitial edema, and deposition of eosinophilic material in the tubule lumen. Electron microscopic findings indicated changes including glomerular epithelial and endothelial cell cytotoxicity as well as disorders of the basement membrane. Tubule alterations include epithelial cell cytotoxicity with cytoplasmic membrane blebs, mitochondrial changes, increase in smooth endoplasmic reticulum, presence of autophagosomes, and deposits of amorphous material in the tubules. We also found that the venom caused azotemia with elevation of blood urea levels but did not decrease C3 complement concentration or cause hemolysis in vivo. Confocal microscopy with antibodies against venom proteins showed direct binding of toxins to renal structures, confirmed by competition assays. Double-staining immunofluorescence reactions with antibodies against type IV collagen or laminin, antibodies to venom toxins, and fluorescent cytochemistry with DAPI revealed deposition of toxins in glomerular and tubule epithelial cells and in renal basement membranes. Two-dimensional electrophoresis showed venom rich in low molecular mass and cationic toxins. By immunoblotting with antibodies to venom toxins on renal extracts from venom-treated mice, we detected a renal binding toxin at 30 kD. The data provide experimental evidence that L. intermedia venom is directly involved in nephrotoxicity. 相似文献
134.
Marcia Helena Appel Rafael Bertoni da Silveira Olga Meiri Chaim Kátia Sabrina Paludo Dilza Trevisan Silva Daniele M. Chaves Paulo Henrique da Silva Oldemir C. Mangili Andrea Senff-Ribeiro Waldemiro Gremski Helena B. Nader Silvio Sanches Veiga 《Biochimica et Biophysica Acta (BBA)/General Subjects》2008
Brown spider bites are associated with lesions including dermonecrosis, gravitational spreading and a massive inflammatory response, along with systemic problems that may include hematological disturbances and renal failure. The mechanisms by which the venom exerts its noxious effects are currently under investigation. It is known that the venom contains a major toxin (dermonecrotic toxin, biochemically a phospholipase D) that can experimentally induce dermonecrosis, inflammatory response, animal mortality and platelet aggregation. Herein, we describe cloning, heterologous expression, purification and functionality of a novel isoform of the 33 kDa dermonecrotic toxin. Circular dichroism analysis evidenced correct folding for the toxin. The recombinant toxin was recognized by whole venom serum antibodies and by a specific antibody to a previously described dermonecrotic toxin. The identified toxin was found to display phospholipase activity and dermonecrotic properties. Additionally, the toxin caused a massive inflammatory response in rabbit skin dermis, evoked platelet aggregation, increased vascular permeability, caused edema and death in mice. These characteristics in combination with functional studies for other dermonecrotic toxins illustrate that a family of dermonecrotic toxins exists, and includes a novel member with high activity that may be useful for future structural and functional studies. 相似文献
135.
Identification of quantitative trait loci associated with resistance to cucumber mosaic virus in Capsicum annuum 总被引:5,自引:0,他引:5
A. Ben Chaim R. C. Grube M. Lapidot M. Jahn I. Paran 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2001,102(8):1213-1220
QTL analysis for resistance to cucumber mosaic virus (CMV) was performed in an intraspecific Capsicum annuum population. A total of 180 F3 families were derived from a cross between the susceptible bell-type cultivar Maor and the resistant
small-fruited Indian line Perennial and inoculated with CMV in three experiments carried out in the USA and Israel using two
virus isolates. Mostly RFLP and AFLP markers were used to construct the genetic map, and interval analysis was used for QTL
detection. Four QTL were significantly associated with resistance to CMV. Two digenic interactions involving markers with
and without an individual effect on CMV resistance were also detected. The QTL controlling the largest percentage (16–33%)
of the observed phenotypic variation (cmv11.1) was detected in all three experiments and was also involved in one of the digenic interactions. This QTL is linked to the
L locus that confers resistance to tobacco mosaic virus (TMV), confirming earlier anecdotal observations of an association
between resistance to CMV and susceptibility to TMV in Perennial. An advanced backcross breeding line from an unrelated population,
3990, selected for resistance to CMV was analyzed for markers covering the genome, allowing the identification of genomic
regions introgressed from Perennial. Four of these introgressions included regions associated with QTL for CMV resistance.
Markers in two genomic regions that were identified as linked to QTL for CMV resistance were also linked to QTL for fruit
weight, confirming additional breeding observations of an association between resistance to CMV originating from Perennial
and small fruit weight.
Received: 17 July 2000 / Accepted: 16 October 2000 相似文献
136.
Summary The late Triassic succession of the Asher-Atlit 1 borehole is over 1000 m thick, and is composed of reefal and associated
facies interbedded with volcanics of Norian age. Only borehole cuttings are available. Microfacies classification and cement
stratigraphy determined by optical and CL microscopy, allowed discrimination of six episodes of reef establishment, progradation,
shallowing, and termination. Organic buildups are constructed of reef-building biota (sponges, possible corals, encrusting
organisms) typical for the late Triassic of the Tethys. Reef-associated facies include fore-slope, central reef, ooid shoal,
lagoonal, and supratidal environments. Cement zoning patterns trace diagenetic signatures which range from early neomorphic
skeletal replacements and original marine cements, via characteristic burial sequences; depositional and diagenetic sequences
are terminated by marginal marine intra- or supratidal conditions, and subaerial exposure with pedogenic overprints. Volcanic
episodes tend to be associated with termination of carbonate sedimentation episodes, while volcanic quiescence and subsidence
permit vertical progradation of reefal and associated facies. The depositional and progradational environment, rapid rate
of sedimentation, periodicity, association with volcanics, and regional considerations, suggest a depositional setting on
the rifted shelf-margin of the nascent Neo-Tethys, with a possible eustatic overprint. 相似文献
137.
Sky1p and Ptk2p are protein kinases that regulate ion transport across the plasma membrane of Saccharomyces cerevisiae. We show here that deletion of SKY1 or PTK2 in trk1,2Delta cells increase spermine tolerance, implying Trk1,2p independent activity. Unexpectedly, trk1,2Deltasky1Delta and trk1,2Deltaptk2Delta cells display hypersensitivity to LiCl. These cells also show increased tolerance to low pH and improved growth in low K(+), as demonstrated for deletion of PMP3 in trk1,2Delta cells. We show that Sky1p and Pmp3p act in different pathways. Hypersensitivity to LiCl and improved growth in low K(+) are partly dependent on the Nha1p and Kha1p antiporters and on the Tok1p channel. Finally, Dhh1p, a RNA helicase was demonstrated to improve growth of trk1,2Deltasky1Delta cells in low K(+). Overexpression of Dhh1p improves the ability of trk1,2Delta cells to grow in low K(+) while dhh1Delta cells are sensitive to spermine and salt ions. A model that integrates these results to explain the mechanism of ion transport across the plasma membrane is proposed. 相似文献
138.
Chaim AB Borovsky Y De Jong W Paran I 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2003,106(5):889-894
The purple color of the foliage, flower and immature fruit of pepper ( Capsicum spp.) is a result of the accumulation of anthocyanin pigments in these tissues. The expression of anthocyanins is controlled by the incompletely dominant gene A. We have mapped A to pepper chromosome 10 in a Capsicum annuum (5226) x Capsicum chinense (PI 159234) F(2) population to a genomic region that also controls anthocyanin expression in two other Solanaceous species, tomato and potato, suggesting that variation for tissue-specific expression of anthocyanin pigments in these plants is controlled by an orthologous gene(s). We mapped an additional locus, Fc, for the purple anther filament in an F(2) population from a cross of IL 579, a C. chinense introgression line and its recurrent parent 100/63, to the same position as A, suggesting that the two loci are allelic. The two anthocyanin loci were linked to a major quantitative trait locus, fs10.1, for fruit-shape index (ratio of fruit length to fruit width), that also segregated in the F(2) populations. This finding verified the observation of Peterson in 1959 of linkage between fruit color and fruit-shape genes in a cross between round and elongated-fruited parents. The linkage relationship in pepper resembles similar linkage in potato, in which anthocyanin and tuber-shape genes were found linked to each other in a cross of round and elongated-tuber parents. It is therefore possible that the shape pattern of distinct organs such as fruit and tuber in pepper and potato is controlled by a similar gene(s). 相似文献
139.
Mitochondrial DNA is subject to increased rates of mutations due to its proximity to the source of reactive oxygen species. Here we show that increased MHC class I (MHC I) expression serves to alert the immune system to cells with mitochondrial mutations. MHC I is overexpressed in fibroblasts with mitochondrial dysfunction from patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes and in lymphocytes from purine nucleoside phosphorylase-deficient immune-deficient mice with mitochondrial DNA deletions. Consistent with a role of MHC I in the elimination of cells containing mitochondrial DNA mutations, mice deficient in MHC I accumulate mitochondrial DNA deletions in various tissues. These observations in both mice and humans suggest a role for the immune system in preventing reversion of mitochondrial DNA back into a parasitic state following deleterious mutations affecting mitochondrial oxidative phosphorylation. 相似文献
140.
Ephrin-A1 induces c-Cbl phosphorylation and EphA receptor down-regulation in T cells 总被引:3,自引:0,他引:3
Sharfe N Freywald A Toro A Roifman CM 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(12):6024-6032
Eph receptor tyrosine kinases are expressed by T lineage cells, and stimulation with their ligands, the ephrins, has recently been shown to modulate T cell behavior. We show that ephrin-A1 stimulation of Jurkat T cells induces tyrosine phosphorylation of EphA3 receptors and cytoplasmic proteins, including the c-cbl proto-oncogene. Cbl phosphorylation was also observed in peripheral blood T cells. In contrast, stimulation of Jurkat cells with the EphB receptor ligand ephrin-B1 does not cause Cbl phosphorylation. EphA activation also induced Cbl association with Crk-L and Crk-II adapters, but not the related Grb2 protein. Induction of Cbl phosphorylation upon EphA activation appeared to be dependent upon Src family kinase activity, as Cbl phosphorylation was selectively abrogated by the Src family inhibitor 4-amino-5(4-chlorophenyl-7-(tert-butyl)pyrazolo[3,4-d]pyrimidine, while EphA phosphorylation was unimpaired. Ephrin-A1 stimulation of Jurkat cells was also found to cause down-regulation of endogenous EphA3 receptors from the cell surface and their degradation. In accordance with the role of Cbl as a negative regulator of receptor tyrosine kinases, overexpression of wild-type Cbl, but not its 70-Z mutant, was found to down-regulate EphA receptor expression. Receptor down-regulation could also be inhibited by blockage of Src family kinase activity. Our findings show that EphA receptors can actively signal in T cells, and that Cbl performs multiple roles in this signaling pathway, functioning to transduce signals from the receptors as well as regulating activated EphA receptor expression. 相似文献