bluuebunny/crossref_metadata_2025_split huggingface dataset:
Membrane estrogen receptor-α levels predict estrogen-induced ERK1/2 activation in MCF-7 cells
Authors: Zivadinovic Dragoslava , Watson Cheryl S 
Published: January 2005

Abstract
Introduction
We examined the participation of a membrane form of estrogen receptor (mER)-α in the activation of mitogen-activated protein kinases (extracellular signal-regulated kinase [ERK]1 and ERK2) related to cell growth responses in MCF-7 cells.

Methods
We immunopanned and subsequently separated MCF-7 cells (using fluorescence-activated cell sorting) into mER-α-enriched (mERhigh) and mER-α-depleted (mERlow) populations. We then measured the expression levels of mER-α on the surface of these separated cell populations by immunocytochemical analysis and by a quantitative 96-well plate immunoassay that distinguished between mER-α and intracellular ER-α. Western analysis was used to determine colocalized estrogen receptor (ER)-α and caveolins in membrane subfractions. The levels of activated ERK1 and ERK2 were determined using a fixed cell-based enzyme-linked immunosorbent assay developed in our laboratory.

Results
Immunocytochemical studies revealed punctate ER-α antibody staining of the surface of nonpermeabilized mERhigh cells, whereas the majority of mERlow cells exhibited little or no staining. Western analysis demonstrated that mERhigh cells expressed caveolin-1 and caveolin-2, and that ER-α was contained in the same gradient-separated membrane fractions. The quantitative immunoassay for ER-α detected a significant difference in mER-α levels between mERhigh and mERlow cells when cells were grown at a sufficiently low cell density, but equivalent levels of total ER-α (membrane plus intracellular receptors). These two separated cell subpopulations also exhibited different kinetics of ERK1/2 activation with 1 pmol/l 17β-estradiol (E2), as well as different patterns of E2 dose-dependent responsiveness. The maximal kinase activation was achieved after 10 min versus 6 min in mERhigh versus mERlow cells, respectively. After a decline in the level of phosphorylated ERKs, a reactivation was seen at 60 min in mERhigh cells but not in mERlow cells. Both 1A and 2B protein phosphatases participated in dephosphorylation of ERKs, as demonstrated by efficient reversal of ERK1/2 inactivation with okadaic acid and cyclosporin A.

Conclusion
Our results suggest that the levels of mER-α play a role in the temporal coordination of phosphorylation/dephosphorylation events for the ERKs in breast cancer cells, and that these signaling differences can be correlated to previously demonstrated differences in E2-induced cell proliferation outcomes in these cell types.
Hypersensitive K303R oestrogen receptor-α variant not found in invasive carcinomas
Authors: Davies Michael PA , O'Neill Penny A , Innes Helen , Sibson D Ross 
Published: January 2005

Abstract
Introduction
Genetic abnormalities or mutations in premalignant breast lesions may have a role in progression toward malignancy or influence the behaviour of subsequent disease. The A908G (Lys303→Arg) change in the gene encoding oestrogen receptor-α (ER-α) creates a hypersensitivity to oestradiol and would have significant consequences if present in breast carcinoma, especially those treated with endocrine therapy. We have therefore examined a panel of endocrine-treated invasive carcinomas for the presence of this mutation.

Methods
Sequencing of control DNA was shown to detect mutation present in as little as 15% of the starting material. Enrichment for the mutation by using MboII restriction digestion allowed the detection of mutant present at 1% or less. We applied these techniques to genomic DNA and cDNA from 136 invasive breast carcinomas.

Results
No evidence of the A908G mutation was found with either technique. The incidence of this mutation in our panel of tumours is therefore significantly less than previously reported.

Conclusion
The fact that the mutation was not found leads us to believe that this mutation is absent from most cells in invasive carcinomas and furthermore that the major expression product of the ER-α gene in cancers does not contain the K303R mutation. It is therefore unlikely to influence the effectiveness of endocrine treatment.
Atm heterozygous deficiency enhances development of mammary carcinomas in p53heterozygous knockout mice
Authors: Umesako Seiichi , Fujisawa Kae , Iiga Sayoko , Mori Nobuko , Takahashi Masahiro , Hong Doo-Pyo , Song Chang-Woo , Haga Satomi , Imai Syunsuke , Niwa Otsura , Okumoto Masaaki 
Published: January 2005

Abstract
Introduction
Ataxia-telangiectasia is an autosomal-recessive disease that affects neuro-immunological functions, associated with increased susceptibility to malignancy, chromosomal instability and hypersensitivity to ionizing radiation. Although ataxia-telangiectasia mutated (ATM) heterozygous deficiency has been proposed to increase susceptibility to breast cancer, some studies have not found excess risk. In experimental animals, increased susceptibility to breast cancer is not observed in the Atm heterozygous deficient mice (Atm+/-) carrying a knockout null allele. In order to determine the effect of Atm heterozygous deficiency on mammary tumourigenesis, we generated a series of Atm+/- mice on the p53+/- background with a certain predisposition to spontaneous development of mammary carcinomas, and we examined the development of the tumours after X-irradiation.

Methods
BALB/cHeA-p53+/- mice were crossed with MSM/Ms-Atm+/- mice, and females of the F1 progeny ([BALB/cHeA × MSM/Ms]F1) with four genotypes were used in the experiments. The mice were exposed to X-rays (5 Gy; 0.5 Gy/min) at age 5 weeks.

Results
We tested the effect of haploinsufficiency of the Atm gene on mammary tumourigenesis after X-irradiation in the p53+/- mice of the BALB/cHeA × MSM/Ms background. The singly heterozygous p53+/- mice subjected to X-irradiation developed mammary carcinomas at around 25 weeks of age, and the final incidence of mammary carcinomas at 39 weeks was 31% (19 out of 61). The introduction of the heterozygous Atm knockout alleles into the background of the p53+/- genotype significantly increased the incidence of mammary carcinoma to 58% (32 out of 55) and increased the average number of mammary carcinomas per mouse. However, introduction of Atm alleles did not change the latency of development of mammary carcinoma.

Conclusion
Our results indicate a strong enhancement in mammary carcinogenesis by Atm heterozygous deficiency in p53+/- mice. Thus, doubly heterozygous mice represent a useful model system with which to analyze the interaction of heterozygous genotypes for p53, Atm and other genes, and their effects on mammary carcinogenesis.
The androgen receptor CAG repeat polymorphism and modification of breast cancer risk in BRCA1 and BRCA2 mutation carriers
Authors: Spurdle Amanda B , Antoniou Antonis C , Duffy David L , Pandeya Nirmala , Kelemen Livia , Chen Xiaoqing , Peock Susan , Cook Margaret R , Smith Paula L , Purdie David M , Newman Beth , Dite Gillian S , Apicella Carmel , Southey Melissa C , Giles Graham G , Hopper John L ,   kConFaB, EMBRACE Study Collaborators, ABCFS, AJBCS, Chenevix-Trench Georgia , Easton Douglas F 
Published: January 2005

Abstract
Introduction
The androgen receptor (AR) gene exon 1 CAG repeat polymorphism encodes a string of 9–32 glutamines. Women with germline BRCA1 mutations who carry at least one AR allele with 28 or more repeats have been reported to have an earlier age at onset of breast cancer.

Methods
A total of 604 living female Australian and British BRCA1 and/or BRCA2 mutation carriers from 376 families were genotyped for the AR CAG repeat polymorphism. The association between AR genotype and disease risk was assessed using Cox regression. AR genotype was analyzed as a dichotomous covariate using cut-points previously reported to be associated with increased risk among BRCA1 mutation carriers, and as a continuous variable considering smaller allele, larger allele and average allele size.

Results
There was no evidence that the AR CAG repeat polymorphism modified disease risk in the 376 BRCA1 or 219 BRCA2 mutation carriers screened successfully. The rate ratio associated with possession of at least one allele with 28 or more CAG repeats was 0.74 (95% confidence interval 0.42–1.29; P = 0.3) for BRCA1 carriers, and 1.12 (95% confidence interval 0.55–2.25; P = 0.8) for BRCA2 carriers.

Conclusion
The AR exon 1 CAG repeat polymorphism does not appear to have an effect on breast cancer risk in BRCA1 or BRCA2 mutation carriers.
Breast implants following mastectomy in women with early-stage breast cancer: prevalence and impact on survival
Authors: Le Gem M , O'Malley Cynthia D , Glaser Sally L , Lynch Charles F , Stanford Janet L , Keegan Theresa HM , West Dee W 
Published: January 2005

Abstract
Background
Few studies have examined the effect of breast implants after mastectomy on long-term survival in breast cancer patients, despite growing public health concern over potential long-term adverse health effects.

Methods
We analyzed data from the Surveillance, Epidemiology and End Results Breast Implant Surveillance Study conducted in San Francisco–Oakland, in Seattle–Puget Sound, and in Iowa. This population-based, retrospective cohort included women younger than 65 years when diagnosed with early or unstaged first primary breast cancer between 1983 and 1989, treated with mastectomy. The women were followed for a median of 12.4 years (n = 4968). Breast implant usage was validated by medical record review. Cox proportional hazards models were used to estimate hazard rate ratios for survival time until death due to breast cancer or other causes for women with and without breast implants, adjusted for relevant patient and tumor characteristics.

Results
Twenty percent of cases received postmastectomy breast implants, with silicone gel-filled implants comprising the most common type. Patients with implants were younger and more likely to have in situ disease than patients not receiving implants. Risks of breast cancer mortality (hazard ratio, 0.54; 95% confidence interval, 0.43–0.67) and nonbreast cancer mortality (hazard ratio, 0.59; 95% confidence interval, 0.41–0.85) were lower in patients with implants than in those patients without implants, following adjustment for age and year of diagnosis, race/ethnicity, stage, tumor grade, histology, and radiation therapy. Implant type did not appear to influence long-term survival.

Conclusions
In a large, population-representative sample, breast implants following mastectomy do not appear to confer any survival disadvantage following early-stage breast cancer in women younger than 65 years old.
Effect of magnesium sulfate administration on blood–brain barrier in a rat model of intraperitoneal sepsis: a randomized controlled experimental study
Authors: Esen Figen , Erdem Tulin , Aktan Damla , Orhan Mukadder , Kaya Mehmet , Eraksoy Haluk , Cakar Nahit , Telci Lutfi 
Published: January 2005

Abstract
Introduction
Permeability changes in the blood–brain barrier (BBB) and their possible contribution to brain edema formation have a crucial role in the pathophysiology of septic encephalopathy. Magnesium sulfate has been shown to have a protective effect on BBB integrity in multiple experimental models. In this study we determine whether magnesium sulfate administration could have any protective effects on BBB derangement in a rat model of sepsis.

Methods
This randomized controlled experimental study was performed on adult male Sprague–Dawley rats. Intraperitoneal sepsis was induced by using the infected fibrin–thrombin clot model. To examine the effect of magnesium in septic and sham-operated rats, a dose of 750 μmol/kg magnesium sulfate was given intramuscularly immediately after surgery. Control groups for both infected and sham-operated rats were injected with equal volume of saline. Those rats surviving for 24 hours were anesthetized and decapitated for the investigation of brain tissue specific gravity and BBB integrity by the spectrophotometric assay of Evans blue dye extravasations. Another set of experiments was performed for hemodynamic measurements and plasma magnesium level analysis. Rats were allocated into four parallel groups undergoing identical procedures.

Results
Sepsis significantly increased BBB permeability to Evans blue. The dye content of each hemisphere was significantly lower in the magnesium-treated septic rats (left hemisphere, 0.00218 ± 0.0005; right hemisphere, 0.00199 ± 0.0007 [all results are means ± standard deviation]) than in control septic animals (left hemisphere, 0.00466 ± 0.0002; right hemisphere, 0.00641 ± 0.0003). In septic animals treated with magnesium sulfate, specific gravity was higher (left hemisphere, 1.0438 ± 0.0007; right hemisphere, 1.0439 ± 0.0004) than in the untreated septic animals (left hemisphere, 1.0429 ± 0.0009; right hemisphere, 1.0424 ± 0.0012), indicating less edema formation with the administration of magnesium. A significant decrease in plasma magnesium levels was observed 24 hours after the induction of sepsis. The dose of magnesium that we used maintained the baseline plasma magnesium levels in magnesium-treated septic rats.

Conclusions
Magnesium administration attenuated the increased BBB permeability defect and caused a reduction in brain edema formation in our rat model of intraperitoneal sepsis.
Aerosolized colistin for the treatment of nosocomial pneumonia due to multidrug-resistant Gram-negative bacteria in patients without cystic fibrosis
Authors: Michalopoulos Argyris , Kasiakou Sofia K , Mastora Zefi , Rellos Kostas , Kapaskelis Anastasios M , Falagas Matthew E 
Published: January 2005

Abstract
Introduction
The clinical and economic consequences of the emergence of multidrug-resistant Gram-negative bacteria in the intensive care unit (ICU) setting, combined with the high mortality rate among patients with nosocomial pneumonia, have stimulated a search for alternative therapeutic options to treat such infections. The use of adjunctive therapy with aerosolized colistin represents one of these. There is extensive experience with use of aerosolized colistin by patients with cystic fibrosis, but there is a lack of data regarding the use of aerosolized colistin in patients without cystic fibrosis.

Methods
We conducted the present study to assess the safety and effectiveness of aerosolized colistin as an adjunct to intravenous antimicrobial therapy for treatment of Gram-negative nosocomial pneumonia. We retrospectively reviewed the medical records of patients hospitalized in a 450-bed tertiary care hospital during the period from October 2000 to January 2004, and who received aerosolized colistin as adjunctive therapy for multidrug-resistant pneumonia.

Results
Eight patients received aerosolized colistin. All patients had been admitted to the ICU, with mean Acute Physiological and Chronic Health Evaluation II scores on the day of ICU admission and on day 1 of aerosolized colistin administration of 14.6 and 17.1, respectively. Six of the eight patients had ventilator-associated pneumonia. The responsible pathogens were Acinetobacter baumannii (in seven out of eight cases) and Pseudomonas aeruginosa (in one out of eight cases) strains. Half of the isolated pathogens were sensitive only to colistin. The daily dose of aerosolized colistin ranged from 1.5 to 6 million IU (divided into three or four doses), and the mean duration of administration was 10.5 days. Seven out of eight patients received concomitant intravenous treatment with colistin or other antimicrobial agents. The pneumonia was observed to respond to treatment in seven out of eight patients (four were cured and three improved [they were transferred to another facility]). One patient deteriorated and died from septic shock and multiple organ failure. Aerosolized colistin was well tolerated by all patients; no bronchoconstriction or chest tightness was reported.

Conclusion
Aerosolized colistin may be a beneficial adjunctive treatment in the management of nosocomial pneumonia (ventilator associated or not) due to multidrug-resistant Gram-negative bacteria.
Estimating genomic coexpression networks using first-order conditional independence
Authors: Magwene Paul M , Kim Junhyong 
Published: January 2005

AbstractWe describe a computationally efficient statistical framework for estimating networks of coexpressed genes. This framework exploits first-order conditional independence relationships among gene-expression measurements to estimate patterns of association. We use this approach to estimate a coexpression network from microarray gene-expression measurements from Saccharomyces cerevisiae. We demonstrate the biological utility of this approach by showing that a large number of metabolic pathways are coherently represented in the estimated network. We describe a complementary unsupervised graph search algorithm for discovering locally distinct subgraphs of a large weighted graph. We apply this algorithm to our coexpression network model and show that subgraphs found using this approach correspond to particular biological processes or contain representatives of distinct gene families.
A Drosophila protein-interaction map centered on cell-cycle regulators
Authors: Stanyon Clement A , Liu Guozhen , Mangiola Bernardo A , Patel Nishi , Giot Loic , Kuang Bing , Zhang Huamei , Zhong Jinhui , Finley Russell L 
Published: January 2005

Abstract
Background
Maps depicting binary interactions between proteins can be powerful starting points for understanding biological systems. A proven technology for generating such maps is high-throughput yeast two-hybrid screening. In the most extensive screen to date, a Gal4-based two-hybrid system was used recently to detect over 20,000 interactions among Drosophila proteins. Although these data are a valuable resource for insights into protein networks, they cover only a fraction of the expected number of interactions.

Results
To complement the Gal4-based interaction data, we used the same set of Drosophila open reading frames to construct arrays for a LexA-based two-hybrid system. We screened the arrays using a novel pooled mating approach, initially focusing on proteins related to cell-cycle regulators. We detected 1,814 reproducible interactions among 488 proteins. The map includes a large number of novel interactions with potential biological significance. Informative regions of the map could be highlighted by searching for paralogous interactions and by clustering proteins on the basis of their interaction profiles. Surprisingly, only 28 interactions were found in common between the LexA- and Gal4-based screens, even though they had similar rates of true positives.

Conclusions
The substantial number of new interactions discovered here supports the conclusion that previous interaction mapping studies were far from complete and that many more interactions remain to be found. Our results indicate that different two-hybrid systems and screening approaches applied to the same proteome can generate more comprehensive datasets with more cross-validated interactions. The cell-cycle map provides a guide for further defining important regulatory networks in Drosophila and other organisms.
MONKEY: identifying conserved transcription-factor binding sites in multiple alignments using a binding site-specific evolutionary model
Authors: Moses Alan M , Chiang Derek Y , Pollard Daniel A , Iyer Venky N , Eisen Michael B 
Published: January 2005

AbstractWe introduce a method (MONKEY) to identify conserved transcription-factor binding sites in multispecies alignments. MONKEY employs probabilistic models of factor specificity and binding-site evolution, on which basis we compute the likelihood that putative sites are conserved and assign statistical significance to each hit. Using genomes from the genus Saccharomyces, we illustrate how the significance of real sites increases with evolutionary distance and explore the relationship between conservation and function.
The Mammalian Phenotype Ontology as a tool for annotating, analyzing and comparing phenotypic information
Authors: Smith Cynthia L , Goldsmith Carroll-Ann W , Eppig Janan T 
Published: January 2005

AbstractThe Mammalian Phenotype (MP) Ontology enables robust annotation of mammalian phenotypes in the context of mutations, quantitative trait loci and strains that are used as models of human biology and disease. The MP Ontology supports different levels and richness of phenotypic knowledge and flexible annotations to individual genotypes. It continues to develop dynamically via collaborative input from research groups, mutagenesis consortia, and biological domain experts. The MP Ontology is currently used by the Mouse Genome Database and Rat Genome Database to represent phenotypic data.
Integration with the human genome of peptide sequences obtained by high-throughput mass spectrometry
Authors: Desiere Frank , Deutsch Eric W , Nesvizhskii Alexey I , Mallick Parag , King Nichole L , Eng Jimmy K , Aderem Alan , Boyle Rose , Brunner Erich , Donohoe Samuel , Fausto Nelson , Hafen Ernst , Hood Lee , Katze Michael G , Kennedy Kathleen A , Kregenow Floyd , Lee Hookeun , Lin Biaoyang , Martin Dan , Ranish Jeffrey A , Rawlings David J , Samelson Lawrence E , Shiio Yuzuru , Watts Julian D , Wollscheid Bernd , Wright Michael E , Yan Wei , Yang Lihong , Yi Eugene C , Zhang Hui , Aebersold Ruedi 
Published: January 2005

AbstractA crucial aim upon the completion of the human genome is the verification and functional annotation of all predicted genes and their protein products. Here we describe the mapping of peptides derived from accurate interpretations of protein tandem mass spectrometry (MS) data to eukaryotic genomes and the generation of an expandable resource for integration of data from many diverse proteomics experiments. Furthermore, we demonstrate that peptide identifications obtained from high-throughput proteomics can be integrated on a large scale with the human genome. This resource could serve as an expandable repository for MS-derived proteome information.
The local isotropy hypothesis and the turbulent kinetic energy dissipation rate in the atmospheric surface layer
Authors: Chamecki M. , Dias N. L. 
Published: January 2005

AbstractWe test the applicability of the local isotropy hypothesis to surface‐layer turbulent flow; turbulent velocities measured with a three‐dimensional sonic anemometer are used for this purpose, and the predictions of local isotropy for the spectra, second‐ and third‐order structure functions are assessed against measured data. Also investigated are scale interactions via the correlation between velocities and velocity increments, and the ability of isotropic spectral models to reproduce measured spectra. In general, second‐order structure functions display a narrower inertial range than the corresponding spectra; both the known effects of path‐averaging and the predictions of the spectral models show that the sonic anemometer is unable to resolve the whole inertial range, even at a measurement frequency of 60 Hz. We confirm previous results that unstable runs tend to be more isotropic, but find that, for third‐order statistics, isotropy does not hold well for the data analysed. Turbulence intensity, and not atmospheric stability, plays a determining role on the correlation coefficient between velocities and velocity increments. The observed anisotropic behaviour has important implications for the calculation of the turbulent kinetic energy dissipation rate from Kolmogorov's four‐fifths law, whose estimates are consistently smaller than those from the inertial range of the spectrum or the structure functions. Copyright © 2004 Royal Meteorological Society