Johns Hopkins University School of Medicine

About: Johns Hopkins University School of Medicine is a healthcare organization based out in Baltimore, Maryland, United States. It is known for research contribution in the topics: Population & Medicine. The organization has 44277 authors who have published 79222 publications receiving 4788882 citations.

Hypoxia, clonal selection, and the role of HIF-1 in tumor progression.

Abstract: Tumor progression occurs as a result of the clonal selection of cells in which somatic mutations have activated oncogenes or inactivated tumor suppressor genes leading to increased proliferation an...

The Female Sexual Distress Scale (FSDS): initial validation of a standardized scale for assessment of sexually related personal distress in women.

Abstract: Recent consensus-based characterizations of female sexual dysfunction have emphasized personal distress as an essential component of their definition. To assist researchers and clinicians, we developed a new scale, the Female Sexual Distress Scale, to measure sexually related personal distress in women. In this article, we describe the initial stages in the development and validation of this instrument. Three studies involving a total of approximately 500 women were performed to evaluate the reliability and validity of the scale in different samples of sexually functional and dysfunctional women. Results indicated a unidimensional factor structure in both the original 20-item version and in a "polished" 12-item version. We observed a high degree of internal consistency and test-retest reliability in both versions across all three studies. Additionally, the scale showed a high degree of discriminative ability to distinguish between sexually dysfunctional and functional women in each of the studies. One study also showed a strong sensitivity to treatment response. Finally, we observed moderate positive correlations with other conceptually related nonsexual measures of distress, supporting the construct validity of the scale. Overall, these findings provide solid support for the FSDS as a valid and reliable measure for assessing sexually related personal distress in women.

Apoptotic photoreceptor cell death in mouse models of retinitis pigmentosa.

Abstract: Retinitis pigmentosa (RP) is a group of inherited human diseases in which photoreceptor degeneration leads to visual loss and eventually to blindness. Although mutations in the rhodopsin, peripherin, and cGMP phosphodiesterase genes have been identified in some forms of RP, it remains to be determined whether these mutations lead to photoreceptor cell death through necrotic or apoptotic mechanisms. In this paper, we report a test of the hypothesis that photoreceptor cell death occurs by an apoptotic mechanism in three mouse models of RP: retinal degeneration slow (rds) caused by a peripherin mutation, retinal degeneration (rd) caused by a defect in cGMP phosphodiesterase, and transgenic mice carrying a rhodopsin Q344ter mutation responsible for autosomal dominant RP. Two complementary techniques were used to detect apoptosis-specific internucleosomal DNA fragmentation: agarose gel electrophoresis and in situ labeling of apoptotic cells by terminal dUTP nick end labeling. Both methods showed extensive apoptosis of photoreceptors in all three mouse models of retinal degeneration. We also show that apoptotic death occurs in the retina during normal development, suggesting that different mechanisms can cause photoreceptor death by activating an intrinsic death program in these cells. These findings raise the possibility that retinal degenerations may be slowed by interfering with the apoptotic mechanism itself.

Impaired physiological responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1α

Abstract: Chronic hypoxia induces polycythemia, pulmonary hypertension, right ventricular hypertrophy, and weight loss. Hypoxia-inducible factor 1 (HIF-1) activates transcription of genes encoding proteins that mediate adaptive responses to hypoxia, including erythropoietin, vascular endothelial growth factor, and glycolytic enzymes. Expression of the HIF-1α subunit increases exponentially as O2 concentration is decreased. Hif1a–/– mouse embryos with complete deficiency of HIF-1α due to homozygosity for a null allele at the Hif1a locus die at midgestation, with multiple cardiovascular malformations and mesenchymal cell death. Hif1a+/– heterozygotes develop normally and are indistinguishable from Hif1a+/+ wild-type littermates when maintained under normoxic conditions. In this study, the physiological responses of Hif1a+/– and Hif1a+/+ mice exposed to 10% O2 for one to six weeks were analyzed. Hif1a+/– mice demonstrated significantly delayed development of polycythemia, right ventricular hypertrophy, pulmonary hypertension, and pulmonary vascular remodeling and significantly greater weight loss compared with wild-type littermates. These results indicate that partial HIF-1α deficiency has significant effects on multiple systemic responses to chronic hypoxia. J. Clin. Invest. 103:691–696 (1999)