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Biomedical subjects

J Schwartz

Publications and source records attributed to J Schwartz.

At least 19 recordsLinked to original sources
PubMed1992

Dihydropyrimidine calcium channel blockers. 4. Basic 3-substituted-4-aryl-1,4-dihydropyrimidine-5-carboxylic acid esters. Potent antihypertensive agents.

We have examined a series of novel dihydropyrimidine calcium channel blockers that contain a basic group attached to either C5 or N3 of the heterocyclic ring. Structure-activity studies show that a 1-(phenylmethyl)-4-piperidinyl carbamate moiety at N3 and sulfur at C2 are optimal for vasorelaxant activity in vitro and impart potent and long-acting antihypertensive activity in vivo. One of these compounds (11) was identified as a lead, and the individual enantiomers 12a (R) and 12b (S) were synthesized. Two key steps of the synthesis were (1) the efficient separation of the diastereomeric ureido derivatives 29a/29b and (2) the high-yield transformation of 2-methoxy intermediates 30a/30b to the (p-methoxybenzyl)thio intermediates 31a/31b. Chirality was demonstrated to be a significant determinant of biological activity, with the dihydropyridine receptor recognizing the enamino ester moiety (12a) but not the carbamate moiety (12b). Dihydropyrimidine 12a is equipotent to nifedipine and amlodipine in vitro. In the spontaneously hypertensive rat, dihydropyrimidine 12a is both more potent and longer acting than nifedipine and compares most favorably with the long-acting dihydropyridine derivative amlodipine. Dihydropyrimidine 12a has the potential advantage of being a single enantiomer.

Amlodipine↗
PubMed1992

A genetic system for studying the activity of a proteolytic enzyme.

We describe a genetic system for monitoring the activity of a specific proteolytic enzyme by taking advantage of the properties of the yeast transcriptional activator GAL4. The GAL4 protein contains two separable and functionally essential domains: the amino-terminal DNA binding domain and the carboxyl-terminal transcriptional activating domain. We constructed two hybrid proteins by inserting between the DNA binding domain and the activation domain of GAL4 either (i) a self-cleaving protease (3C protease of a picornavirus, coxsackievirus B3) or (ii) a mutant form of the protease that is unable to cleave. We show that, although the hybrid protein containing the mutant protease activates transcription of GAL1-lacZ reporter gene, the hybrid protein bearing the wild-type protease is proteolytically cleaved and fails to activate transcription. Our approach to monitor the proteolytic activity could be used to develop simple genetic systems to study other proteases.

Amino Acid Sequence↗
PubMed1992

Particulate air pollution and daily mortality in Steubenville, Ohio.

Particulate air pollution has been associated with daily mortality in London, England, both in the smog episodes of the 1950s and at the lower pollution levels of the late 1960s and early 1970s. Replicating these findings in the United States has been difficult, because particulates are usually sampled every sixth day. Replication, particularly with a gravimetric measure of particulates, is important in assessing the causality of the relation. Daily measurements of total suspended particulates by high volume gravimetric sampler are available for the Steubenville, Ohio, metropolitan area. These were matched to daily mortality counts from the detail mortality tapes of the National Center for Health Statistics. Deaths of residents which occurred outside the Steubenville Standard Metropolitan Statistical Area were excluded. Because of the much smaller population, the average total number of deaths per day in the Steubenville Standard Metropolitan Statistical Area over the 11-year period 1974-1984 was about 1% of the deaths in a typical London winter. Despite this reduced statistical power, total suspended particulate count was significantly associated with increased daily mortality in Poisson regression analyses controlling for season and temperature. An increase in particulates of 100 micrograms/m3 was associated with a 4% increase in mortality on the succeeding day. Associations with sulfur dioxide were not significant after adjustment for particulates. The relation appeared to continue at levels well below the current National Ambient Air Quality Standard.

Air Pollutants↗
PubMed1992

The impact of anticipation of job loss on psychological distress and worksite blood pressure.

The impact of occupational stressful life events on psychological distress and blood pressure was examined among employees of a major New York City brokerage firm undergoing massive layoffs. One hundred thirty-nine employees of the firm, who had participated in a blood pressure screening in 1986, were rescreened during the period of layoffs within their company in 1989. About two-thirds of the 139 employees reported being "somewhat" or "very" anxious or upset in 1989 during the period of layoffs, and psychological distress was significantly elevated among those employees reporting possible or definite layoff or job change and/or difficulty in obtaining a comparable job. However, we found no increase in overall blood pressure level, and no effect of anticipation of job loss on 1989 blood pressure when controlling for 1986 blood pressure level, age, body mass index, work hours, and other demographic variables. On the other hand, employment in a department sold to another employer on the day of screening, as well as employment in a clerical job title, were both associated with significant increases in diastolic blood pressure of about 5 mm Hg.

Anxiety↗
PubMed1992

The use of asymmetric-field inversion gel electrophoresis to predict tumor cell radiosensitivity.

The success of a predictive assay for radiotherapy relies on the use of one or more tumor cell traits that equate with tumor radioresistance or radiosensitivity. These traits can be divided into intrinsic (genetic) and extrinsic (epi-genetic) factors. Most probably, a tumor's response to radiotherapy will be influenced by both of these sets of traits. Radiobiological analysis of cultured cells derived from explanted tumors of head and neck patients has shown that in vitro survival of tumor cells is not the only factor affecting tumor radiocurability. Two possible reasons are the high degree of selection involved in growing the cells in vitro and the inability to assess the contribution of the cell-cell contact effect with cultured cells. A possible means of overcoming both of these problems would be an assessment of the radiosensitivity of the cell population immediately after removal from the tumor. Since a good correlation exists between intrinsic cellular radioresistance and DNA double-strand break repair (DSBR) as assayed by the Neutral Elution technique [21], we have investigated the feasibility of using asymmetric field inversion gel electrophoresis (AFIGE) in identifying resistant tumor cells in vitro. AFIGE has several advantages over neutral elution in that it is faster (approximately 60-80 samples can be run on the same agarose gel) and, most importantly, one can visualize DNA damage and repair by staining the DNA with ethidium bromide.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon Radioisotopes↗
PubMed1992

The selective cytotoxic effect of carotenoids and alpha-tocopherol on human cancer cell lines in vitro.

This study compares the toxic effects of the carotenoids, beta-carotene and canthaxanthin, and alpha-tocopherol (vitamin E) on human tumor cells and their normal counterparts in vitro. Seven different malignant cell lines were examined: oral carcinoma (two cell lines), breast (two cell lines), lung carcinoma (two cell lines), and malignant melanoma. The in vitro cell culture assays showed a consistent morphologic change in the affected tumor cells following treatment with carotenoid or vitamin E. A rounding of the tumor cells and eventual lifting off the tissue culture plate were observed. These changes were apparent after 1 to 5 hours of treatment depending on the tumor cell line. Associated with these observable cellular changes were quantitative reductions in proliferation (3H-thymidine proliferation) and succinic dehydrogenase activity (MTT assay). In addition, there was a noticeable change in protein expression, with an increased expression of a 70-kD protein following treatment with beta-carotene. This protein was associated with tumor cells showing a decrease in proliferation (oral carcinoma, malignant melanoma) but not with normal keratinocytes or melanocytes. These studies substantiate a selective cytotoxic effect on human tumor cell growth by carotenoids and alpha-tocopherol in vitro, and may provide an explanation of the therapeutic activity of these agents and their possible use in the treatment of premalignancy or early oral carcinoma.

Breast Neoplasms↗
PubMed1992

Caffeine intake and asthma symptoms.

Methylxanthines in the form of coffee and tea may be dietary factors that function as pharmacologic bronchodilators. To examine this hypothesis, we analyzed data from the Second National Health and Nutrition Examination Survey (NHANES II). NHANES II was conducted on a sample representative of the civilian noninstitutionalized US population, which included white and black adults aged 30 years or older. We examined the relationship of usual coffee and tea consumption from a medical history questionnaire to the presence of asthma and wheezing symptoms. Subjects who drank coffee on a regular basis had a 29% reduction in the odds of having current asthma symptoms (odds ratio, 0.71; 95% confidence interval, 0.55 to 0.93) when compared with non-coffee drinkers. The effect exhibited a significant dose-response relationship, with the number of cups of coffee consumed per day being inversely related to asthma prevalence. This relationship was independent of age, gender, and cigarette smoking. Tea consumption was not significantly related to asthma prevalence in this cohort.

Adult↗
PubMed1992

Air pollution and daily mortality: associations with particulates and acid aerosols.

The association between total daily mortality and air pollution was investigated for a 1-year period (September 1985 through August 1986) in St. Louis and in the counties in eastern Tennessee surrounding Kingston/Harriman. The purpose of this study was to evaluate the relative importance of various measures of particulate and gaseous air pollution as predictors of daily mortality. Concentrations of inhalable particles (PM10), fine particles (PM2.5), the elemental composition of these particles, and aerosols acidity were measured daily during the period of study. The effect of each air pollutant on daily mortality was estimated after controlling for meteorologic and seasonal influences. Total mortality in St. Louis was found to increase 16% (95% CI-1 to 33%) for each 100 micrograms/m3 increase in PM10, and by 17% (95% CI-12 to 57%) in eastern Tennessee. Positive but progressively weaker associations were found with PM2.5, sulfate, and aerosol acidity concentrations in both communities. Associations with gaseous pollutants--sulfur dioxide, nitrogen dioxide, and ozone--were all far from statistical significance. Because of the short monitoring period for daily particulate air pollution, the power of this study to detect associations was limited. Nevertheless, statistically significant associations with PM10 were found in St. Louis, and, more importantly, the estimated effects were consistent between the two communities studied and with other reported analyses of the effects of particles on daily mortality. These data suggest that the acidity of particles is not as important in associations with daily mortality as the mass concentrations of particles.

Aerosols↗
PubMed1992

Nightmare prevalence in the healthy elderly.

Fifty-one healthy elderly subjects (median age = 65) gave retrospective estimates of nightmare frequency in questionnaires and recorded the occurrence of nightmares in daily logs over a 2-week period. (a) Mean annual nightmare frequency as estimated from logs was only 65% as high among college student controls. (b) Elderly subjects were about 1/5 as likely as college students to report a problem with nightmares. (c) Frequency estimates on the basis of logs were over 10 times higher than retrospective estimates.

Aged↗
PubMed1992

The short-term psychological health of alcoholic and non-alcoholic liver transplant recipients.

In response to limited resources and overwhelming clinical need, we previously developed an approach to alcoholic patient selection for liver transplant based on factors reported to predict short- and long-term sobriety in prospective studies of alcoholics. The present study reports follow-up data comparing alcohol dependent (n = 22, DSM-3-R criteria) and non-dependent (n = 39) subjects followed from 6 months to 3 years post-transplant. Nine percent of the alcoholics had returned to symptomatic drinking with 14% reporting some exposure to ethyl alcohol. Nearly half (46%) of the non-alcoholic group reported occasional social alcohol use. The alcoholic patients were less likely to be in their first marriage and more likely to be asked about alcohol use at follow-up clinic visits. In most other respects the two groups resembled each other more often than they differed. The alcoholic group reported continued high rates of prognostic factors associated with long-term abstinence although the content of these shifted noticeably between pre- and postoperative assessment. Members of both groups reported high frequencies of medication side effects, of missed doses of medications, and of depressive symptoms. Most felt the transplant had improved their lives but had brought on significant financial burden. There were no differences in subjective appraisals of either psychological or physical health between the two groups. These follow-up data suggest that carefully selected alcohol dependent patients will do as well as non-dependent patients after liver transplant.

Adaptation, Psychological↗
PubMed1992

Air pollution and respiratory symptoms in preschool children.

A diary study on a random sample of 625 Swiss children aged 0 to 5 yr was conducted in two cities in Switzerland to investigate the association between air pollution and respiratory symptoms. Total suspended particulates (TSP), SO2 and NO2 were measured by city monitor. In addition, passive samplers inside and outside the home measured NO2 concentration during the 6 wk each child was on the diary. Diaries were filled out by parents, and 20% were validated with the attending pediatrician's case notes. Incidence and duration of symptom episodes were examined separately. The study included any episode, episodes of coughing without runny nose, upper respiratory episodes, and episodes of breathing difficulty. In regressions using 6-wk average pollution that controlled for medical history, NO2 measured outdoors but not indoors was associated with the duration of any symptom. Total suspended particulates were a more significant predictor of duration of any symptom than NO2. The 6-wk average TSP was significantly associated with incidence of coughing episodes and marginally significant as a predictor of upper respiratory episodes. Previous day's TSP was a significant predictor of incidence of upper respiratory symptoms. Annual average of NO2 was associated with the duration of any episode and of upper respiratory episodes. We conclude that the incidence and duration of respiratory symptom episodes are likely associated with particulate concentrations and duration may be associated with NO2.

Air Pollution↗
PubMed1992

Increased mortality in Philadelphia associated with daily air pollution concentrations.

Cause-specific deaths by day for the years 1973 to 1980 in Philadelphia, Pennsylvania, were extracted from National Center for Health Statistics mortality tapes. Death from accidents (International Classification of Disease, Revision 9 greater than or equal to 800) and deaths outside of the city were excluded. Daily counts of deaths were regressed using Poisson regression on total suspended particulate (TSP) and/or SO2 on the same day and on the preceding day, controlling for year, season, temperature, and humidity. A significant positive association was found between total mortality (mean of 48 deaths/day) and both TSP (second highest daily mean, 222 micrograms/m3) and SO2 (second highest daily mean, 299 micrograms/m3). The strongest associations were found with the mean pollution of the current and the preceding days. Total mortality was estimated to increase by 7% (95% CI, 4 to 10%) with each 100-micrograms/m3 increase in TSP, and 5% (95% CI, 3 to 7%) with each 100-micrograms/m3 increase in SO2. When both pollutants were considered simultaneously, the SO2 association was no longer significant. Mortality increased monotonically with TSP. The effect of 100 micrograms/m3 TSP was stronger in subjects older than 65 yr of age (10% increase) compared with those younger than 65 yr of age (3% increase). Cause-specific mortality was also associated with a 100-micrograms/m3 increase in TSP: chronic obstructive pulmonary disease (ICD9 490-496), +19% (95% CI, 0 to 42%), pneumonia (ICD9 480-486 & 507), +11% (95% CI, -3 to +27%), and cardiovascular disease (ICD9 390-448), +10% (95% CI, 6 to 14%). These results are somewhat higher than previously reported associations, and they add to the body of evidence showing that particulate pollution is associated with increased daily mortality at current levels in the United States.

Age Factors↗