Database of mutations in the p53 and APC tumor suppressor genes designed to facilitate molecular epidemiological analyses

Germline and somatic mutations in the p53 and APC genes contribute to neoplasia. The patterns of these and other acquired mutations in cancers reflect environmental mutagens and endogenous factors that contribute to carcinogenesis. Herein, we describe a database of almost 2,300 mutations in the p53 and APC genes published until September 1, 1993. In addition to cataloging the mutations, multiple fields of information have been added to facilitate future molecular epidemiological analyses of human cancer. The accuracy of the database has been checked by the present authors and, by soliciting feedback from the original corresponding authors. The strengths and limitations of the primary literature are discussed.     

Pneumatic dilatation is effective long-term treatment for achalasia

Although pneumatic dilatation (PD) has been an established treatment for achalasia for decades, there is limited information on its long-term clinical efficacy. We have followed up the clinical status of patients having PD with a 30- or 35-mm balloon by one of us (D.O.C.) over a 25-year period. Of 144 patients whose initial records were available for review, 31 could not be contacted. Of the remaining 113 patients, 72 (64%) responded to a questionnaire assessing swallowing status and patient satisfaction, and this forms the basis of this report. There were 32 men and 40 women, with mean age 46 years (range: 17-78); mean length of follow-up since PD was 6.5 years (range: 10 months to 25 years). Success was primarily defined by the need for no additional therapy for achalasia other than one or two PD's. PD was effective long-term treatment in 61/72 patients (85%); only four of these required a second PD over this time interval. There was no significant difference in any of the following parameters between patients with a treatment success or failure: age, sex, size of pneumatic dilator, and duration of symptoms prior to PD. Response was significantly better (P < 0.05) in patients having no prior dilatation (43/47; 91%) than in those in whom another physician had performed prior dilatation (18/25; 72%). In response to the question of whether they would select PD again, 68 patients (94%) responded positively. In conclusion, pneumatic dilatation performed using a consistent technique by an experienced physician is effective long-term therapy for achalasia patients of all ages. Most patients require only one dilatation.     

Mating-related stimulation induces phosphorylation of dopamine- and cyclic AMP-regulated phosphoprotein-32 in progestin receptor-containing areas in the female rat brain

Vaginal-cervical stimulation induces a number of physiological and behavioral events, including the facilitation of mating behavior. Although the facilitation of one component of mating behavior, lordosis, by vaginal-cervical stimulation does not require the presence of progesterone, it appears to be mediated by neural progestin receptors. Abundant evidence suggests that dopamine may play a role in the neural circuitry activated by vaginal-cervical stimulation, including the mating-induced release of dopamine in progestin receptor-containing areas of the brain, changes in the activational state of progestin receptors because of dopamine D1 receptor stimulation, facilitation of lordosis by D1 receptor stimulation in estradiol-primed rats via progesterone-independent events, and D1 agonist-induced neuronal responses in progestin receptor-containing areas and cells. We tested the hypothesis that vaginal-cervical stimulation induces phosphorylation of dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32; Mr = 32,000), a protein phosphorylated predominantly in response to the stimulation of D1 receptors. At 9 d after ovariectomy, female rats were injected subcutaneously with a behaviorally effective dose of estradiol benzoate. At 48 hr later they received vaginal-cervical or control (perineal) stimulation, and they were perfused 1 hr later. Vaginal-cervical stimulation increased the number of cells expressing pDARPP-32 immunoreactivity by 92% in the medial preoptic nucleus, 134% in the caudal ventromedial hypothalamic nucleus, 123% in the posterodorsal medial amygdala, and 103% in the bed nucleus of the stria terminalis. These results suggest that some of the neuronal effects of vaginal-cervical stimulation, and perhaps other social or environmental stimuli, are mediated by phosphorylation of DARPP-32, perhaps via stimulation of D1 receptors, within progestin receptor-containing areas.     

A review of new oncotropic tracers for PET imaging

We have developed three biochemical probes to determine if they are sensitive probes of early biochemical change in a tumor. All three probes appear to have the appropriate properties for in vivo imaging, but must now be evaluated as probes for the sensitive detection of changes in early malignant disease.     

Involvement of polyamines in the protection of taurine against the cytotoxicity of hydrazine or carbon tetrachloride in isolated rat hepatocytes

Taurine (2-aminoethanesulfonic acid) is known to protect hepatocyte injury induced by hydrazine or carbon tetrachloride. We investigated whether cellular polyamines are involved in the protective mechanism of taurine in the hepatocyte injury caused by hydrazine or carbon tetrachloride. The agents decreased cellular polyamine concentrations, but the treatment with taurine prevented this decrease. The protection of taurine against hepatic injury was not observed in hepatocytes treated with alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase which is a key enzyme in polyamine biosynthesis. The protection of taurine was recovered by the addition of polyamines to DFMO-treated hepatocytes. These results suggest that cellular polyamines play an important role in the protection of taurine in hydrazine or carbon tetrachloride-induced hepatocyte injury.     

Cataract extraction rates in Olmsted County, Minnesota, 1980 through 1994

Management of Q-wave acute myocardial infarction (AMI) has been shown to differ between the United States and Canada, with more catheterization and revascularization procedures performed in the United States, but with little or no apparent difference in clinical outcomes. No previous studies have evaluated management differences for the acute coronary syndromes of unstable angina pectoris and non-Q-wave AMI. We therefore compared treatments and outcomes between 14 United States and 4 Canadian tertiary care centers participating in an observational registry of all consecutive admissions for unstable angina or non-Q-wave AMI between 1990 and 1993. A random, stratified sample was selected for detailed assessment and follow-up. There were 1,733 patients enrolled in United States centers and 642 in Canadian ones. In United States centers patients were less likely to receive intravenous nitroglycerin, heparin, beta blockers, calcium antagonists, or > or = 2 anti-ischemic agents. Coronary arteriography during index hospitalization was equally frequent in both countries (63.4% vs 66.9%, p = 0.781), but at 6 weeks and 1 year coronary arteriography was slightly less frequent in the United States patients. Revascularization by coronary angioplasty or bypass surgery was equivalent at 6 weeks and 1 year; however, there were trends toward less angioplasty and more bypass surgery in the United States than in Canada. Patients at United States centers stayed in the hospital fewer days than patients at Canadian centers (mean 8.2 vs 12.1 days, p <0.001). Death or AMI by 6 weeks was not different (4.8% vs 4.4%, p = 0.633), nor was it different at 1 year (10.0% vs 10.2%, p = 0.836). The combined outcome of death, AMI, or recurrent ischemia was more common in United States than in Canadian patients at 6 weeks (18.4% vs 13.9%, p = 0.004). Our findings indicate that United States physicians and hospitals did not consistently utilize more resources and were not more aggressive than their Canadian counterparts when treating acute coronary syndromes during this period.     

Changing personality patterns of police officers.

Twenty-five police officers were evaluated at or shortly after their recruitment and again 2 years later. Eleven of the officers were available for follow-up 4 years after recruitment. Minnesota Multiphasic Personality Inventory (MMPI) scores showed significant changes over time, suggesting increasing somatic symptoms, anxiety, and alcohol vulnerability. The increased vulnerability to alcohol abuse was the strongest finding, and by the 4th year of service, mean MacAndrews Alcoholism Scale scores were within the critical range. Results are discussed in terms of the peculiar stresses of police work and the need for periodic reevaluation to prevent stress-associated problems and also initiate early intervention programs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Problems associated with rabies preexposure prophylaxis

With the rabies vaccine presently available for preexposure prophylaxis, 20% of all individuals do not have seroconversion following routine immunizations, and 5% are allergic to this vaccine. Two experimental rabies vaccines of cell culture origin offering greater purity and potency were evaluated by means of a double-blind experiment. Thirty-one volunteers who did not have seroconversion or who were allergic to duck embryo rabies vaccine received rabies vaccine produced in either human diploid cell culture (WI-38), or hamster kidney-cell culture. All volunteers had seroconversion within 14 days of receiving a single injection of other experimental vaccine. Clinical side effects were only minor.     

Pinning of Austenite Grain Boundaries by

The growth behavior of austenite grains in the presence of A1N precipitates varies with the temperature and time of anneal. To study this behavior, two iron alloys, (in weight percent) a 0.1 carbon base chemistry with 0.03A1/0.01N and 0.09A1/0.04N, respectively, were annealed between 1000 °C and 1200 °C for times of up to 180 minutes. Using optical microscopy, as many as 1000 austenite grains per heat-treatment condition were measured. Conditions of sup- pressed, abnormal, and uniform grain growth were observed. Using an extraction replica tech- nique, the size, shape, and distribution of the A1N particles were determined using transmission electron microscopy (TEM). The largest grain boundary curvatures calculated, using the Hellman- Hillert pinning model, were in close agreement with independent calculations of curvatures using the grain size data. The largest grains in the lognormal size distribution of austenite grains were found to be the ones with the potential to grow to abnormally large sizes.     

Justifying multimachine systems: An integrated strategic approach

Current problems in justifying multimachine systems are analyzed and an integrated framework is developed in which both strategic and tactical considerations are included. At the strategic level the tools for project selection are reviewed, followed by the economic analysis normally required for these systems. Special tools, notably simulation, are illustrated through an example situation.