Institution
University of California, San Francisco
Education•San Francisco, California, United States•
About: University of California, San Francisco is a education organization based out in San Francisco, California, United States. It is known for research contribution in the topics: Population & Health care. The organization has 83381 authors who have published 186236 publications receiving 12068420 citations. The organization is also known as: UCSF & UC San Francisco.
Topics: Population, Health care, Cancer, Medicine, Transplantation
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University of California, Los Angeles1, Medical University of South Carolina2, Rutgers University3, University of Illinois at Chicago4, Boston University5, Johns Hopkins University6, Georgetown University7, University of Texas Health Science Center at Houston8, Wayne State University9, University of California, San Francisco10, University of Alabama11, University of Connecticut12
TL;DR: One year of oral cyclophosphamide in patients with symptomatic scleroderma-related interstitial lung disease had a significant but modest beneficial effect on lung function, dyspnea, thickening of the skin, and the health-related quality of life.
Abstract: BACKGROUND We conducted a double-blind, randomized, placebo-controlled trial to determine the effects of oral cyclophosphamide on lung function and health-related symptoms in patients with evidence of active alveolitis and scleroderma-related interstitial lung disease. METHODS At 13 clinical centers throughout the United States, we enrolled 158 patients with scleroderma, restrictive lung physiology, dyspnea, and evidence of inflammatory interstitial lung disease on examination of bronchoalveolar-lavage fluid, thoracic highresolution computed tomography, or both. Patients received oral cyclophosphamide (≤2 mg per kilogram of body weight per day) or matching placebo for one year and were followed for an additional year. Pulmonary function was assessed every three months during the first year, and the primary end point was the forced vital capacity (FVC, expressed as a percentage of the predicted value) at 12 months, after adjustment for the baseline FVC. RESULTS Of 158 patients, 145 completed at least six months of treatment and were included in the analysis. The mean absolute difference in adjusted 12-month FVC percent predicted between the cyclophosphamide and placebo groups was 2.53 percent (95 percent confidence interval, 0.28 to 4.79 percent), favoring cyclophosphamide (P<0.03). There were also treatment-related differences in physiological and symptom outcomes, and the difference in FVC was maintained at 24 months. There was a greater frequency of adverse events in the cyclophosphamide group, but the difference between the two groups in the number of serious adverse events was not significant. CONCLUSIONS One year of oral cyclophosphamide in patients with symptomatic sclerodermarelated interstitial lung disease had a significant but modest beneficial effect on lung function, dyspnea, thickening of the skin, and the health-related quality of life. The effects on lung function were maintained through the 24 months of the study.
1,330 citations
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TL;DR: In this paper, the α6/β4 heterodimer was found to play a significant role in directing polarity and tissue structure of mammary epithelial cells, suggesting the existence of intimate interactions between different integrin pathways as well as adherens junctions.
Abstract: In a recently developed human breast cancer model, treatment of tumor cells in a 3-dimensional culture with inhibitory β1-integrin antibody or its Fab fragments led to a striking morphological and functional reversion to a normal phenotype. A stimulatory β1-integrin antibody proved to be ineffective. The newly formed reverted acini re-assembled a basement membrane and re-established E-cadherin–catenin complexes, and re-organized their cytoskeletons. At the same time they downregulated cyclin D1, upregulated p21cip,waf-1, and stopped growing. Tumor cells treated with the same antibody and injected into nude mice had significantly reduced number and size of tumors in nude mice. The tissue distribution of other integrins was also normalized, suggesting the existence of intimate interactions between the different integrin pathways as well as adherens junctions. On the other hand, nonmalignant cells when treated with either α6 or β4 function altering antibodies continued to grow, and had disorganized colony morphologies resembling the untreated tumor colonies. This shows a significant role of the α6/β4 heterodimer in directing polarity and tissue structure. The observed phenotypes were reversible when the cells were disassociated and the antibodies removed. Our results illustrate that the extracellular matrix and its receptors dictate the phenotype of mammary epithelial cells, and thus in this model system the tissue phenotype is dominant over the cellular genotype.
1,329 citations
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TL;DR: APR-induced alterations initially protect the host from the harmful effects of bacteria, viruses, and parasites, however, if prolonged, these changes in the structure and function of lipoproteins will contribute to atherogenesis.
1,328 citations
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TL;DR: Findings support the role of SMO as a signalling component of the SHH–receptor complex and provide direct evidence that mutated SMO can function as an oncogene in BCCs.
Abstract: Basal-cell carcinomas (BCCs) are the commonest human cancer. Insight into their genesis came from identification of mutations in the PATCHED gene (PTCH) in patients with the basal-cell nevus syndrome, a hereditary disease characterized by multiple BCCs and by developmental abnormalities. The binding of Sonic hedgehog (SHH) to its receptor, PTCH, is thought to prevent normal inhibition by PTCH of Smoothened (SMO), a seven-span transmembrane protein. According to this model, the inhibition of SMO signalling is relieved following mutational inactivation of PTCH in basal-cell nevus syndrome. We report here the identification of activating somatic missense mutations in the SMO gene itself in sporadic BCCs from three patients. Mutant SMO, unlike wild type, can cooperate with adenovirus E1A to transform rat embryonic fibroblast cells in culture. Furthermore, skin abnormalities similar to BCCs developed in transgenic murine skin overexpressing mutant SMO. These findings support the role of SMO as a signalling component of the SHH-receptor complex and provide direct evidence that mutated SMO can function as an oncogene in BCCs.
1,328 citations
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TL;DR: Direct evidence is presented that NMDA receptors exist in rat neocortex as heteromeric complexes of considerable heterogeneity, some containing both NR2A and NR2B subunits.
Abstract: ACTIVATION of the N-methyl-d-aspartate (NMDA) receptor is important for certain forms of activity-dependent synaptic plasticity, such as long-term potentiation (reviewed in ref. 1), and the patterning of connections during development of the visual system (reviewed in refs 2, 3). Several subunits of the NMDA receptor have been cloned: these are NMDAR1 (NR1), and NMDAR2A, 2B, 2C and 2D (NR2A-D)4–8. Based on heterologous co-expression studies, it is inferred that NR1 encodes an essential subunit of NMDA receptors and that functional diversity of NMDA receptors in vivo is effected by differential incorporation of subunits NR2A–NR2D5–8. Little is known, however, about the actual subunit composition or heterogeneity of NMDA receptors in the brain. By co-immunoprecipitation with subunit-specific antibodies, we present here direct evidence that NMDA receptors exist in rat neocortex as heteromeric complexes of considerable heterogeneity, some containing both NR2A and NR2B subunits. A progressive alteration in subunit composition seen postnatally could contribute to NMDA-receptor variation and changing synaptic plasticity during cortical development.
1,328 citations
Authors
Showing all 84066 results
Name | H-index | Papers | Citations |
---|---|---|---|
Robert Langer | 281 | 2324 | 326306 |
Meir J. Stampfer | 277 | 1414 | 283776 |
Gordon H. Guyatt | 231 | 1620 | 228631 |
Eugene Braunwald | 230 | 1711 | 264576 |
John Q. Trojanowski | 226 | 1467 | 213948 |
Fred H. Gage | 216 | 967 | 185732 |
Robert J. Lefkowitz | 214 | 860 | 147995 |
Peter Libby | 211 | 932 | 182724 |
Edward Giovannucci | 206 | 1671 | 179875 |
Rob Knight | 201 | 1061 | 253207 |
Irving L. Weissman | 201 | 1141 | 172504 |
Eugene V. Koonin | 199 | 1063 | 175111 |
Peter J. Barnes | 194 | 1530 | 166618 |
Virginia M.-Y. Lee | 194 | 993 | 148820 |
Gordon B. Mills | 187 | 1273 | 186451 |