p53: a frequent target for genetic abnormalities in lung cancer   总被引：124，自引：0，他引：124  

T Takahashi  M M Nau  I Chiba  M J Birrer  R K Rosenberg  M Vinocour  M Levitt  H Pass  A F Gazdar  J D Minna 《Science (New York, N.Y.)》1989,246(4929):491-494

Allele loss is a hallmark of chromosome regions harboring recessive oncogenes. Lung cancer frequently demonstrates loss of heterozygosity on 17p. Recent evidence suggests that the p53 gene located on 17p13 has many features of such an antioncogene. The p53 gene was frequently mutated or inactivated in all types of human lung cancer. The genetic abnormalities of p53 include gross changes such as homozygous deletions and abnormally sized messenger RNAs along with a variety of point or small mutations, which map to the p53 open reading frame and change amino acid sequence in a region highly conserved between mouse and man. In addition, very low or absent expression of p53 messenger RNA in lung cancer cell lines compared to normal lung was seen. These findings, coupled with the previous demonstration of 17p allele loss in lung cancer, strongly implicate p53 as an anti-oncogene whose disruption is involved in the pathogenesis of human lung cancer.  相似文献   

The immune response to anesthesia: Part 2 sedatives,opioids, and injectable anesthetic agents     

Stacy L Anderson  Tanya Duke‐Novakovski  Baljit Singh 《Veterinary anaesthesia and analgesia》2014,41(6):553-566

ObjectiveTo review the immune response to injectable anesthetics and sedatives and to compare the immunomodulatory properties between inhalation and injectable anesthetic protocols.Study designReview.Methods and databasesMultiple literature searches were performed using PubMed and Google Scholar from March 2012 through November 2013. Relevant anesthetic and immune terms were used to search databases without year published or species constraints. The online database for Veterinary Anaesthesia and Analgesia and the Journal of Veterinary Emergency and Critical Care were searched by issue starting in 2000 for relevant articles.ConclusionSedatives, injectable anesthetics, opioids, and local anesthetics have immunomodulatory effects that may have positive or negative consequences on disease processes such as endotoxemia, generalized sepsis, tumor growth and metastasis, and ischemia-reperfusion injury. Therefore, anesthetists should consider the immunomodulatory effects of anesthetic drugs when designing anesthetic protocols for their patients.  相似文献   

Microbiology and evolution. Modulating mutation rates in the wild     

Rosenberg SM  Hastings PJ 《Science (New York, N.Y.)》2003,300(5624):1382-1383

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Density is only relative     

Daniels S 《Science (New York, N.Y.)》2005,310(5748):621

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Notes and double knocks from Arkansas     

Charif RA  Cortopassi KA  Figueroa HK  Fitzpatrick JW  Fristrup KM  Lammertink M  Luneau MD  Powers ME  Rosenberg KV 《Science (New York, N.Y.)》2005,309(5740):1489

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Population dynamics of exploited fish stocks at low population levels     

Myers RA  Barrowman NJ  Hutchings JA  Rosenberg AA 《Science (New York, N.Y.)》1995,269(5227):1106-1108

Models of population dynamics in which per capita reproductive success declines at low population levels (variously known as depensation, the Allee effect, and inverse density-dependence) predict that populations can have multiple equilibria and may suddenly shift from one equilibrium to another. If such depensatory dynamics exist, reduced mortality may be insufficient to allow recovery of a population after abundance has been severely reduced by harvesting. Estimates of spawner abundance and number of surviving progeny for 128 fish stocks indicated only 3 stocks with significant depensation. Estimates of the statistical power of the tests strengthen the conclusion that depensatory dynamics are not apparent for fish populations at the levels studied.  相似文献   

Distinctive roles of PHAP proteins and prothymosin-alpha in a death regulatory pathway   总被引：1，自引：0，他引：1  

Jiang X  Kim HE  Shu H  Zhao Y  Zhang H  Kofron J  Donnelly J  Burns D  Ng SC  Rosenberg S  Wang X 《Science (New York, N.Y.)》2003,299(5604):223-226

A small molecule, alpha-(trichloromethyl)-4-pyridineethanol (PETCM), was identified by high-throughput screening as an activator of caspase-3 in extracts of a panel of cancer cells. PETCM was used in combination with biochemical fractionation to identify a pathway that regulates mitochondria-initiated caspase activation. This pathway consists of tumor suppressor putative HLA-DR-associated proteins (PHAP) and oncoprotein prothymosin-alpha (ProT). PHAP proteins promoted caspase-9 activation after apoptosome formation, whereas ProT negatively regulated caspase-9 activation by inhibiting apoptosome formation. PETCM relieved ProT inhibition and allowed apoptosome formation at a physiological concentration of deoxyadenosine triphosphate. Elimination of ProT expression by RNA interference sensitized cells to ultraviolet irradiation-induced apoptosis and negated the requirement of PETCM for caspase activation. Thus, this chemical-biological combinatory approach has revealed the regulatory roles of oncoprotein ProT and tumor suppressor PHAP in apoptosis.  相似文献   

Familial hypophosphatemic rickets: defective transport of inorganic phosphate by intestinal mucosa   总被引：8，自引：0，他引：8  

E M Short  H J Binder  L E Rosenberg 《Science (New York, N.Y.)》1973,179(74):700-702

Uptake of inorganic phosphate is impared in intestinal mucosa from hemizygous males and heterozygous females with X-linked familial hypophosphatemic rickets. Considerable intrafamilial and interfamilial variation in uptake of inorganic phosphate is observed in affected patients. Uptake by normal mucosa is concentrative and energy-dependent, and is mediated by at least two systems with widely different affinities. These results lend direct support to the thesis that the primary metabolic disturbance in this disease results from impaired transport of inorganic phosphate in kidney and gut.  相似文献   

Accuracy of an Adrenocorticotropic Hormone (ACTH) Immunoluminometric Assay for Differentiating ACTH-Dependent from ACTH-Independent Hyperadrenocorticism in Dogs     

M.I. Rodríguez Piñeiro  G. Benchekroun  P. de Fornel-Thibaud  C. Maurey-Guenec  F. Garnier  D. Rosenberg 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2009,23(4):850-855

Background: Adrenocorticotropic hormone (ACTH) determination has been used for 30 years to distinguish ACTH-dependent hyperadrenocorticism (ADHAC) from ACTH-independent hyperadrenocorticism (AIHAC) in dogs. However, the few studies that have evaluated its diagnostic accuracy, based in the majority of cases on older assays, have been associated with systematic, but highly variable proportions of misclassified or unclassified cases.
Objective: The purpose of the present study is to evaluate the accuracy of a validated ACTH immunoluminometric assay (ILMA) for differentiating between ADHAC and AIHAC.
Animals: One hundred and nine dogs with hyperadrenocorticism were included: 91 with ADHAC and 18 with AIHAC.
Methods: Retrospective study. Dogs displaying feedback inhibition after the dexamethasone suppression test, adrenal symmetry, or both were considered to have ADHAC. AIHAC was demonstrated by adrenal tumor histology. For each group, ACTH determination by ILMA was reviewed.
Results: In the ADHAC group, plasma ACTH measurements ranged between 6 and 1250 pg/mL (median, 30 pg/mL). In the AIHAC group, all ACTH concentrations were below the lower quantification limit of the assay (<5 pg/mL). The 95% confidence interval was 85–100% for sensitivity and 97–100% for specificity in AIHAC diagnosis.
Conclusion and Clinical Importance: No overlap in ACTH concentrations was observed between dogs with ADHAC and dogs with AIHAC. The use of a new technique with high analytical sensitivity made it possible to use a low threshold (5 pg/mL), avoiding the misclassification of some ADHAC cases with low, but quantifiable concentrations of ACTH. The assessment of ACTH concentrations by ILMA is an accurate tool for differentiating between ADHAC and AIHAC.  相似文献   

Thyroid Function and Infertility in the Dog: A Survey in Five Breeds     

V Segalini  T Hericher  A Grellet  D Rosenberg  F Garnier  A Fontbonne 《Reproduction in domestic animals》2009,44(S2):211-213

In our study, a clinical and reproductive examination was undertaken in 204 dogs of five different breeds. Thyroxine and thyroid-stimulating hormone plasma concentrations were assayed in order to assess the real incidence of hypothyroidism associated with reproductive disease. Among these animals, only two breeds were affected by hypothyroidism (4.5% of the Dogue de Bordeaux and 2.4% of the Leonbergers). Moreover, these animals did not suffer from any reproductive disease. Our study showed also that 70% of the male Dogue de Bordeaux were hypothyroxinemic compared with Great Danes, English Mastiff and Leonbergers whose male population was 100% normothyroidic. We found the same tendency in bitches. In our data, there was no difference in thyroxin plasma concentrations between normo- and hypofertile dogs, but our results were not statistically significant.  相似文献