Activation of p53 following ionizing radiation, but not other stressors, is dependent on the proline-rich domain (PRD).

The tumor suppressor protein, p53 is one of the most important cellular defences against malignant transformation. In response to cellular stressors p53 can induce apoptosis, cell cycle arrest or senescence as well as aid in DNA repair. Which p53 function is required for tumor suppression is unclear. The proline-rich domain (PRD) of p53 (residues 58-101) has been reported to be essential for the induction of apoptosis. To determine the importance of the PRD in tumor suppression in vivo we previously generated a mouse containing a 33-amino-acid deletion (residues 55-88) in p53 (mΔpro). We showed that mΔpro mice are protected from T-cell tumors but not late-onset B-cell tumors. Here, we characterize the functionality of the PRD and show that it is important for mediating the p53 response to DNA damage induced by γ-radiation, but not the p53-mediated responses to Ha-Ras expression or oxidative stress. We conclude that the PRD is important for receiving incoming activating signals. Failure of PRD mutants to respond to the activating signaling produced by DNA damage leads to impaired downstream signaling, accumulation of mutations, which potentially leads to late-onset tumors.

The extraordinary influences of two British physicians on medical education and practice in Texas at the turn of the 20th century.

In 1891, two British doctors emigrated to Galveston, Texas to become professors in a new medical school. During long and outstanding careers, William Keiller and James Edwin Thompson transferred the best of Old World traditions in anatomy and surgery. The University of Texas Medical Branch became an outstanding teaching institution because of their dedication to professional excellence.

Pneumococcal vaccination in a remote population of high-risk Alaska Natives.

In response to an increasing prevalence of serious pneumococcal disease among adult Alaska Natives of northwest Alaska, a 3-year program was begun in 1987 to identify residents of that remote region who were at high risk for developing invasive pneumococcal disease, to determine their pneumococcal vaccination status, and to deliver vaccine to at least 80 percent of those at risk. After reviewing public health nursing and Indian Health Service data bases, the authors identified 1,337 persons, 20 percent of the 6,692 residents of the region, at high risk for invasive pneumococcal infection, defined either by having a specific chronic disease or by age criteria. Cardiovascular disease and alcoholism were the two most common chronic diseases. Only 30 percent of those determined to be at high risk had received one or more doses of pneumococcal vaccine previously. Half of those persons had received their most recent vaccination 6 or more years earlier. The program used both customary and innovative methods to deliver 23-valent polysaccharide vaccine to 1,046 of those at high risk (78 percent), including 388 persons who were revaccinated. At the completion of the project, 1,123 persons, 84 percent of those at high risk, had received at least 1 dose. They included 1,088 persons, 81 percent of those at high risk, with vaccination within the previous 5 years as a result of the project, compared with a 15-percent rate prior to the vaccination phase of the project. The program demonstrated that high levels of vaccination against pneumococcal disease, exceeding Year 2000 objectives of 60 percent, are attainable in a remote rural Alaskan population.

MMPI identification of nonrehabilitants among disabled veterans.

Utilized the Minnesota Multiphasic Personality Inventory (MMPI) with IQ scores and selected biographic data to identify drop-outs in a Veterans Administration vocational rehabilitation program. Subjects were 61 male disabled veterans. Data were collected at VA Hospital Richmond, Virginia, between September 1973 and September 1974. Follow-up six months after entrance into training utilized persistence in training or employment as success criteria. Multivariate analysis identified 32 of 33 successful and 25 of 28 unsuccessful subjects with p less than .001. Factor analysis of the best predictors identified MMPI Psychopathic deviate (Pd) Hypomania (Ma), and Lie (L) scales which was interpreted to be a social adjustment factor. Four other factors were identified. Results indicated the MMPI was a useful instrument in the identification of disabled veterans who were likely to experience difficulty in post-hospital vocational rehabilitation.