Case Western Reserve University

About: Case Western Reserve University is a education organization based out in Cleveland, Ohio, United States. It is known for research contribution in the topics: Population & Health care. The organization has 54617 authors who have published 106568 publications receiving 5071613 citations. The organization is also known as: Case & Case Western.

Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells.

Abstract: Tumor progression is driven by genetic mutations, but little is known about the environmental conditions that select for these mutations. Studying the transcriptomes of paired colorectal cancer cell lines that differed only in the mutational status of their KRAS or BRAF genes, we found that GLUT1, encoding glucose transporter-1, was one of three genes consistently up-regulated in cells with KRAS or BRAF mutations. The mutant cells exhibited enhanced glucose uptake and glycolysis and survived in low-glucose conditions, phenotypes that all required GLUT1 expression. In contrast, when cells with wild-type KRAS alleles were subjected to a low-glucose environment, very few cells survived. Most surviving cells expressed high levels of GLUT1, and 4% of these survivors had acquired KRAS mutations not present in their parents. The glycolysis inhibitor 3-bromopyruvate preferentially suppressed the growth of cells with KRAS or BRAF mutations. Together, these data suggest that glucose deprivation can drive the acquisition of KRAS pathway mutations in human tumors.

The Effect of Adenosine and Adenine Nucleotides on the Cyclic Adenosine 3',5'-Phosphate Content of Guinea Pig Cerebral Cortex Slices

Abstract: The content cyclic adenosine 39,59-phosphate in guinea pig cerebral cortex slices increases 20-30-fold after a 5-min exposure to a medium containing 0.05 mM adenosine. A similar increase was observed upon exposure to adenine nucleotides. The effect appeared to be specific for adenine ribose monomers. Methylxanthines (0.5 mM) blocked the effect of adenosine, but the blockade could be surmounted by increasing the adenosine concentration. Mutual potentiation of effects was observed when norepinephrine or histamine was added together with adenosine. Nucleotidase activity was observed in slices and homogenates. While this may be related to the mechanism of the adenosine effect, a direct effect of adenosine on adenyl cyclase or cyclic 39,59-nucleotide phosphodiesterase could not be implicated in homogenates. Changes in the tissue compartmentation of adenine nucleotides probably play a major role in producing the previously observed increase of cyclic adenosine 39,59-phosphate during electrical stimulation of slices.

Self-Presentational Motivations and Personality Differences in Self-Esteem

Abstract: This article discusses the interpersonal motivations associated with different levels of self-esteem. Although self-esteem literally refers to an intrapsychic attitude, we propose that self-esteem scales often measure a self-presentational orientation. High self-esteem scores are associated with a tendency to present oneself in a self-enhancing fashion that is characterized by willingness to accept risks, focus on outstandingly good qualities, strategic ploys, and calling attention to self. Low self-esteem scores are associated with a tendency to present oneself in a self-protective fashion that is characterized by unwillingness to accept risks, focus on avoiding outstandingly bad qualities, avoidance of many strategic ploys, and reluctance to draw attention to self. Considerable evidence shows that most people rate themselves as above average on self-esteem scales; relatively few people score below any self-esteem scale's conceptual midpoint. Review of past literature yields the following conclusions: (a) Low scores on self-esteem scales are typically the result of neutral and intermediate rather than self-derogatory responses to scale items; (b) behavioral correlates of measured self-esteem sometimes depend on self-presentational variables such as audience presence; and (c) many past findings with self-esteem scales may be interpretable in self-presentational terms.

Hematopoietic Engraftment and Survival in Adult Recipients of Umbilical-Cord Blood from Unrelated Donors

Abstract: Background Umbilical-cord blood from unrelated donors who are not HLA-identical with the recipients can restore hematopoiesis after myeloablative therapy in children. We studied the use of transplantation of umbilical-cord blood to restore hematopoiesis in adults. Methods Sixty-eight adults with life-threatening hematologic disorders received intensive chemotherapy or total-body irradiation and then transplants of HLA-mismatched umbilical-cord blood. We evaluated the outcomes in terms of hematologic reconstitution, the occurrence of acute and chronic graft-versus-host disease (GVHD), relapses, and event-free survival. Results Of the 68 patients, 48 (71 percent) received grafts of umbilical-cord blood that were mismatched for two or more HLA antigens. Of the 60 patients who survived 28 days or more after transplantation, 55 had neutrophil engraftment at a median of 27 days (range, 13 to 59). The estimated probability of neutrophil recovery in the 68 patients was 0.90 (95 percent confidence interval, 0.85 t...