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S Fields

Publications and source records attributed to S Fields.

At least 37 records · Page 2Linked to original sources
PubMed2000

Constitutive activation of the Saccharomyces cerevisiae transcriptional regulator Ste12p by mutations at the amino-terminus.

The transcriptional activator Ste12p is required for the expression of genes induced by mating pheromone in the yeast Saccharomyces cerevisiae. We identified mutations in the amino-terminal DNA-binding domain of Ste12p that lead to constitutively high-level transcription of pheromone-induced genes. The behaviour of these mutant proteins is consistent with an enhanced DNA-binding ability. Cells carrying these hyperactive proteins retain their sensitivity to pheromone treatment, and their phenotype is largely dependent on the presence of at least one of the MAP kinases (Fus3p or Kss1p) and the scaffold protein Ste5p. Deletion of either FUS3 or KSS1 leads to a marked increase in Ste12p activity, consistent with a negative regulatory role for Fus3p, similar to that described for Kss1p. The properties of the constitutive mutants support the idea that the pheromone response pathway plays a role in basal as well as pheromone-induced transcription.

Blotting, Western↗
PubMed2000

Improved mammographic interpretation of masses using computer-aided diagnosis.

The aim of this study was to evaluate the effectiveness of computerized image enhancement, to investigate criteria for discriminating benign from malignant mammographic findings by computer-aided diagnosis (CAD), and to test the role of quantitative analysis in improving the accuracy of interpretation of mass lesions. Forty sequential mammographically detected mass lesions referred for biopsy were digitized at high resolution for computerized evaluation. A prototype CAD system which included image enhancement algorithms was used for a better visualization of the lesions. Quantitative features which characterize the spiculation were automatically extracted by the CAD system for a user-defined region of interest (ROI). Reference ranges for malignant and benign cases were acquired from data generated by 214 known retrospective cases. The extracted parameters together with the reference ranges were presented to the radiologist for the analysis of 40 prospective cases. A pattern recognition scheme based on discriminant analysis was trained on the 214 retrospective cases, and applied to the prospective cases. Accuracy of interpretation with and without the CAD system, as well as the performance of the pattern recognition scheme, were analyzed using receiver operating characteristics (ROC) curves. A significant difference (p < 0.005) was found between features extracted by the CAD system for benign and malignant cases. Specificity of the CAD-assisted diagnosis improved significantly (p < 0.02) from 14 % for the conventional assessment to 50 %, and the positive predictive value increased from 0.47 to 0.62 (p < 0.04). The area under the ROC curve (A(z)) increased significantly (p < 0. 001) from 0.66 for the conventional assessment to 0.81 for the CAD-assisted analysis. The A(z) for the results of the pattern recognition scheme was higher (0.95). The results indicate that there is an improved accuracy of diagnosis with the use of the mammographic CAD system above that of the unassisted radiologist. Our findings suggest that objective quantitative features extracted from digitized mammographic findings may help in differentiating between benign and malignant masses, and can assist the radiologist in the interpretation of mass lesions.

Breast Neoplasms↗
PubMed2000

Optimizing parameters for computer-aided diagnosis of microcalcifications at mammography.

RATIONALE AND OBJECTIVES: The purpose of this study was to optimize selection of the mammographic features most useful in discriminating benign from malignant clustered microcalcifications. MATERIALS AND METHODS: The computer-aided diagnosis (CAD) system automatically extracted from digitized mammograms 13 quantitative features characterizing microcalcification clusters. Archival cases (n = 134; patient age range, 31-77 years; mean age, 56.8 years) with known histopathologic results (79 malignant, 55 benign) were selected. Three radiologists at three facilities independently analyzed the microcalcifications by using the CAD system. Stepwise discriminant analysis selected the features best discriminating benign from malignant microcalcifications. A classification scheme was constructed on the basis of these optimized features, and its performance was evaluated by using receiver operating characteristic (ROC) analysis. RESULTS: Six of the 13 variables extracted by the CAD system were selected by stepwise determinant analysis for generating the classification scheme, which yielded an ROC curve with an area (Az) of 0.98, specificity of 83.64%, positive predictive value of 89.53%, and accuracy of 91.79% for 98% sensitivity. When patient age was an additional variable, the scheme's performance improved, but this was not statistically significant (Az = 0.98). The ROC curve of the classifier (without age as an additional variable) yielded a high Az of 0.96 for patients younger than 50 years and an even higher (P < .02) Az of 0.99 for those 50 years or older. CONCLUSION: Stepwise discriminant analysis optimized performance of a classification scheme for microcalcifications by selecting six optimized features. Scheme performance was significantly (P < .02) higher for women 50 years or older, but the addition of patient age as a variable did not produce a statistically significant increase in performance.

Adult↗
PubMed2000

Path analysis on the risk of mortality in very low birth weight infants.

OBJECTIVE: The purpose of this work is to clarify by path analysis which of the predictor factors of mortality in a cohort of 423 singletons VLBW infants born at Beilinson Medical Center during the years 1980-1990 (pre-surfactant era) exert direct or indirect effect on mortality. A direct risk factor was defined as a factor having an immediate effect on the outcome without working through an intermediate variable. By contrast, an indirect risk factor was defined as a factor that does not have a direct effect on the risk of mortality but instead works through an intermediate variable. Evaluation of mortality was done at three points over time (pre-delivery, at birth and post-delivery). RESULTS: In the pre-delivery model, gestational age, appropriateness for gestational age, mother's age and fetal distress work directly on mortality in VLBW infants. At birth, mother's age, birth weight and Apgar score at the fifth minute work directly on the risk of mortality. When the assessment of the risk of death was done post-delivery, mother's age, birth weight, Apgar score at the fifth minute and seizures influence directly on mortality risk, and fetal distress, gestational age and pre-natal induced hypertension (PIH) operate indirectly on the risk of mortality. CONCLUSION: The methodology we have used can be adopted in other investigations to distinguish and measure the effect of prognostic factors on the risk of an outcome.

Causality↗
PubMed2000

Grass-roots genomics.

In these heady days of genomic enterprise, the wet-bench geneticist may wonder what the future holds in store for those who explore biology in the laboratory. We argue that the goal of genomics is to serve geneticists.

Animals↗
PubMed2000

A network of protein-protein interactions in yeast.

A global analysis of 2,709 published interactions between proteins of the yeast Saccharomyces cerevisiae has been performed, enabling the establishment of a single large network of 2,358 interactions among 1,548 proteins. Proteins of known function and cellular location tend to cluster together, with 63% of the interactions occurring between proteins with a common functional assignment and 76% occurring between proteins found in the same subcellular compartment. Possible functions can be assigned to a protein based on the known functions of its interacting partners. This approach correctly predicts a functional category for 72% of the 1,393 characterized proteins with at least one partner of known function, and has been applied to predict functions for 364 previously uncharacterized proteins.

Algorithms↗
PubMed2000

Quantitative characterization of mass lesions on digitized mammograms for computer-assisted diagnosis.

RATIONALE AND OBJECTIVES: To investigate features for discriminating benign from malignant mammographic findings by using computer-aided diagnosis (CAD) and to test the accuracy of CAD interpretations of mass lesions. METHODS: Fifty-five sequential, mammographically detected mass lesions, referred for biopsy, were digitized for computerized reevaluation with a CAD system. Quantitative features that characterize spiculation were automatically extracted by the CAD system. Data generated by 271 known retrospective cases were used to set reference values indicating the range for malignant and benign lesions. After conventional interpretation of the 55 prospective cases, they were evaluated a second time by the radiologist using the extracted features and the reference ranges. In addition, a pattern-recognition scheme based on the extracted features was used to classify the prospective cases. Accuracy of interpretation with and without the CAD system was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Sensitivity of the CAD diagnosis for the prospective cases improved from 92% to 100%. Specificity improved significantly from 26.7% to 66.7%. This was accompanied by a significant increase in the accuracy of diagnosis from 56.4% to 81.8% and in the positive predictive value from 51.1% to 71.4%. The Az for the CAD ROC curve significantly increased from 0.73 to 0.90. The performance of the classification scheme was slightly lower than that of the radiologists' interpretation with the CAD system. CONCLUSIONS: Use of the CAD system significantly improved the accuracy of diagnosis. The findings suggest that the classification scheme may improve the radiologist's ability to differentiate benign from malignant mass lesions in the interpretation of mammograms.

Adult↗
PubMed2000

Case 29

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Journal Article↗
PubMed1999

A biochemical genomics approach for identifying genes by the activity of their products.

For the identification of yeast genes specifying biochemical activities, a genomic strategy that is rapid, sensitive, and widely applicable was developed with an array of 6144 individual yeast strains, each containing a different yeast open reading frame (ORF) fused to glutathione S-transferase (GST). For the identification of ORF-associated activities, strains were grown in defined pools, and GST-ORFs were purified. Then, pools were assayed for activities, and active pools were deconvoluted to identify the source strains. Three previously unknown ORF-associated activities were identified with this strategy: a cyclic phosphodiesterase that acts on adenosine diphosphate-ribose 1"-2" cyclic phosphate (Appr>p), an Appr-1"-p-processing activity, and a cytochrome c methyltransferase.

Adenosine Diphosphate Ribose↗
PubMed1999

Functional genomics.

Complete genome sequences are providing a framework to allow the investigation of biological processes by the use of comprehensive approaches. Genome analysis also is having a dramatic impact on medicine through its identification of genes and mutations involved in disease and the elucidation of entire microbial gene sets. Studies of the sequences of model organisms, such as that of the nematode worm Caenorhabditis elegans, are providing extraordinary insights into development and differentiation that aid the study of these processes in humans. The field of functional genomics seeks to devise and apply technologies that take advantage of the growing body of sequence information to analyze the full complement of genes and proteins encoded by an organism.

Animals↗
PubMed1999

Genetic selection of peptide inhibitors of biological pathways.

Genetic selections were used to find peptides that inhibit biological pathways in budding yeast. The peptides were presented inside cells as peptamers, surface loops on a highly expressed and biologically inert carrier protein, a catalytically inactive derivative of staphylococcal nuclease. Peptamers that inhibited the pheromone signaling pathway, transcriptional silencing, and the spindle checkpoint were isolated. Putative targets for the inhibitors were identified by a combination of two-hybrid analysis and genetic dissection of the target pathways. This analysis identified Ydr517w as a component of the spindle checkpoint and reinforced earlier indications that Ste50 has both positive and negative roles in pheromone signaling. Analysis of transcript arrays showed that the peptamers were highly specific in their effects, which suggests that they may be useful reagents in organisms that lack sophisticated genetics as well as for identifying components of existing biological pathways that are potential targets for drug discovery.

Amino Acid Sequence↗
PubMed1999

Caspase-3 inhibits growth in Saccharomyces cerevisiae without causing cell death.

Caspase-3, a member of the caspase family of cell death proteases, cleaves cytoplasmic and nuclear substrates and promotes apoptotic cell death in mammalian cells. Although yeast homologs of apoptotic genes have not been identified, some components of apoptotic pathways retain function in yeast. Here we show that the expression of caspase-3 delays cell growth in Saccharomyces cerevesiae without causing cell death. Mutation of the caspase-3 QACRG active site abolished effects on yeast growth. Co-expression of caspase inhibitors alleviated growth inhibition in yeast as did the tripeptide caspase inhibitor ZVAD-fmk. These results suggest that substrates for caspase-3 are present in S. cerevesiae and may participate in the normal cell growth and division processes.

Apoptosis↗
PubMed1999

Topotecan treatment of adults with primary malignant glioma. The Brain Tumor Center at Duke.

BACKGROUND: Topotecan activity was evaluated for the treatment of malignant glioma. METHODS: Sixty-three patients with newly diagnosed (n = 25) or recurrent (n = 38) malignant glioma were treated with topotecan [AU: Please verify all dosages here and throughout text.]at a dose of 2.6 mg/m2 over a 72-hour period weekly. Recurrent tumors included glioblastoma multiforme (GBM) (n = 28) and anaplastic astrocytoma (AA) (n = 10). Newly diagnosed tumors included GBM (n = 14), AA (n = 8), and anaplastic oligodendroglioma (n = 3). RESULTS: Partial responses were observed in 2 of 14 evaluable patients with newly diagnosed GBM, 1 of 8 patients with newly diagnosed AA, 3 of 10 patients with recurrent AA, and none of 28 patients with recurrent GBM. Four patients with recurrent AA and 7 patients with recurrent GBM demonstrated stable disease (range, 8-52 weeks; median, 21 weeks). Toxicity was limited to infrequent National Cancer Institute Common Toxicity Criteria Grade 3 myelosuppression. CONCLUSIONS: These results suggest that topotecan has modest activity against malignant glioma and continued evaluation of its effectiveness may be warranted when alternative schedules or combination regimens are used.

Adult↗