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Biomedical subjects

J Schwartz

Publications and source records attributed to J Schwartz.

At least 343 records · Page 19Linked to original sources
PubMed1990

Failure of ceftibuten to alter single dose theophylline clearance.

Twelve volunteers participated in a two-way crossover trial in which the effects of ceftibuten on the pharmacokinetics of theophylline were evaluated. Subjects were given single intravenous doses of theophylline (4 mg/kg) with no ceftibuten treatment and on the sixth day of ceftibuten treatment. Ceftibuten 200 mg was taken orally twice daily (7:00 AM and 7:00 PM). A total of 13 blood samples per subject were collected over 48 hours following theophylline administration. Ceftibuten failed to alter either the systemic clearance of theophylline (CL), its volume of distribution (Vss), or its elimination half-life (t1/2). The 24-hour plasma theophylline concentration measured both by high performance liquid chromatography (HPLC) or fluorescence polarization immunoassay (FPIA) was used for a single sample estimate of theophylline clearance (CL), and it was found to provide a suitable estimate of the multisample value for CL.

Administration, Oral↗
PubMed1990

Effect of compounds which disrupt proton gradients on secretion of neurosecretory proteins from PC12 pheochromocytoma cells.

Treatment of PC12 cells with chroquine (10-50 microM) obliterated the low intragranular pH, as detected by Acridine Orange fluorescence, and depleted the cells of dopamine and norepinephrine. However, these concentrations of chloroquine did not prevent the release of the newly synthesized proteins which normally undergo stimulus-coupled secretion with the catecholamines. Higher concentrations of chloroquine (200 microM) and ammonium chloride (10 and 25 mM) inhibited the release of most of these proteins. This inhibition did not result from alterations in protein synthesis, since the profile of proteins synthesized was not substantially altered. Nor did the inhibition result from degradation of the neurosecretory proteins, since prelabeled proteins were capable of undergoing stimulated secretion from chloroquine-treated cells, as from normal cells. The findings indicated that the inhibition was at the step of packaging of the proteins into the neurosecretory granules. While release of the major secretory proteins, including chromogranin B, was inhibited with 200 microM chloroquine, chromogranin A was secreted upon stimulation of these cells. The results of this study indicate that an acidic intragranular pH is not a requirement for the packaging and secretion of neurosecretory proteins. Higher concentrations of chloroquine had a differential effect on the regulated secretion of different neurosecretory proteins.

Adrenal Gland Neoplasms↗
PubMed1990

Dihydropyrimidine calcium channel blockers: 2-heterosubstituted 4-aryl-1,4-dihydro-6-methyl-5-pyrimidinecarboxylic acid esters as potent mimics of dihydropyridines.

2-Heterosubstituted-4-aryl-1,4-dihydro-6-methyl-5-pyrimidinecar box ylic acid esters 8, which lack the potential CS symmetry of dihydropyridine calcium channel blockers, were prepared and evaluated for biological activity. Biological assays using potassium-depolarized rabbit aorta and radioligand binding techniques showed that some of these compounds are potent mimics of dihydropyridine calcium channel blockers. The combination of a branched ester (e.g. isopropyl, sec-butyl) and an alkylthio group (e.g. SMe) was found to be optimal for biological activity. When compared directly with similarly substituted 2-heteroalkyldihydropyridines 9, dihydropyrimidines 8 were found to be 30-fold less active. The solid-state structure of dihydropyrimidine analogue 8g shows that these compounds can adopt a molecular conformation which is similar to the reported conformation of dihydropyridine calcium channel blockers.

Animals↗
PubMed1990

Dihydropyrimidine calcium channel blockers. 2. 3-substituted-4-aryl-1,4-dihydro-6-methyl-5-pyrimidinecarboxylic acid esters as potent mimics of dihydropyridines.

To enhance the intrinsic potency of dihydropyrimidine calcium channel blockers, we have modified the structure of previously described 2-heteroalkyl-1,4-dihydropyrimidines 2 to 3-substituted 1,4-dihydropyrimidines 3. Structure-activity studies using potassium-depolarized rabbit aorta show that ortho, meta-disubstituted aryl derivatives are more potent than either ortho- or meta-monosubstituted compounds. While vasorelaxant activity was critically dependent on the size of the C5 ester group, isopropyl ester being the best, a variety of substituents (carbamate, acyl, sulfonyl, alkyl) were tolerated at N3. Our results show dihydropyrimidines 3 are significantly more potent than corresponding 2-heteroalkyl-1,4-dihydropyrimidines 2 and only slightly less potent than similarly substituted 2-heteroalkyl-1,4-dihydropyridines 4 and 5. Whereas dihydropyridine enantiomers usually show 10-15-fold difference in activity, the enantiomers of dihydropyrimidine 3j show more than a 1000-fold difference in activity. These results strengthen the requirement of an enamino ester for binding to the dihydropyridine receptor and indicate a nonspecific role for the N3-substituent.

Animals↗
PubMed1990

The vir locus affects the response of Bordetella pertussis to antibiotics: phenotypic tolerance and control of autolysis.

Eradication of Bordetella pertussis from the respiratory tract occurs slowly even when bactericidal antibiotics are used. The rate of killing of B. pertussis was found to be proportional to growth rate: virulent, slowly growing strains were killed over days, while rapidly growing strains (either avirulent or virulent modulated by growth conditions to avirulent) were killed over hours. Minimum inhibitory concentrations and binding of antibiotics to membrane targets were equivalent in virulent and avirulent cells, suggesting differences in antibiotic response might reflect differences in activities of the autolytic cascade. This was supported by the finding that cell wall degradation was less than 40% per day in virulent strains and greater than 70% per day in avirulent strains. Penem antibiotics, known to rapidly kill even slowly growing bacteria, demonstrated a more-than-twofold greater rate of killing of slowly growing virulent strains compared with ampicillin or erythromycin. This suggests the potential for improved therapeutic efficacy in vivo. Thus, the vir locus, which determines phase transition in B. pertussis, is apparently the first example of a sensor-transducer system controlling phenotypic tolerance and antibiotic-induced autolytic activity.

Anti-Bacterial Agents↗
PubMed1990

Mortality and air pollution in London: a time series analysis.

The relation between air pollution and mortality in London was examined for the winters of 1958-1972. The data exhibited a high degree of autocorrelation, requiring analyses using autoregressive models. There was a highly significant relation between mortality and either particulate matter or sulfur dioxide (after controlling for temperature and humidity), both overall and in each individual year. Graphic analysis revealed a nonlinear relation with no threshold, and a steeper exposure-response curve at lower air pollution levels. In models with both pollutants, particulate matter remained a significant predictor with about a 10% reduction in its estimated coefficients, while sulfur dioxide was insignificant, with a large drop in its estimated coefficient. The authors conclude that particulates are strongly associated with mortality rates in London, and the relation is likely causal.

Air Pollution↗
PubMed1990

Dietary factors and their relation to respiratory symptoms. The Second National Health and Nutrition Examination Survey.

Dietary factors may influence inflammatory and antioxidant activity, and hence the development of chronic respiratory symptoms. To examine this hypothesis, the authors 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 9,074 white and black adults aged 30 years or older. Dietary factors were derived from serum levels and from a 24-hour dietary recall questionnaire. The authors examined the relations of these dietary factors to the presence of currently active respiratory symptoms. The relation of serum vitamin C, dietary vitamin C intake, dietary fish intake, the ratio of dietary sodium to dietary potassium, and the ratio of serum zinc to serum copper to the respiratory symptoms of bronchitis and wheezing was assessed. Initially, nutrient-specific logistic regression analysis was performed, controlling for age, race, sex, calories, and pack-years of cigarette smoking. When multiple nutrients and total caloric intake were considered for each respiratory symptom outcome, bronchitis was negatively associated with serum vitamin C and with the serum zinc:copper ratio and was positively associated with the sodium:potassium ratio. Wheezing was negatively associated with serum vitamin C, niacin, and the serum zinc:copper ratio. Interactions between nutrients and smoking status were not significant. These data suggest that several dietary constituents may influence the occurrence of respiratory symptoms in adults, independently of cigarette smoking.

Adult↗
PubMed1990

Multinational trends in cancer mortality rates. Methodological issues and results.

Identification of trends in cancer mortality rates for specific sites is useful both for targeting areas of health concern and for suggesting topics where epidemiologic research into etiology might be fruitful. Differences and similarities across countries may provide clues for further research. Counts of cancer mortality by sites are often considered as Poisson processes. Using this framework, Poisson regressions can be used to identify time trends. Model identification can also be difficult and is aided by the graphical techniques of exploratory data analysis. Plots of the data can identify the existence of trends, nonlinearities, cohorts with special risks, and artifacts due to such things as ICD revision. Because human perception is often distorted by outliers in the data, local nonparametric smoothing can yield more robust plots for model identification. Quasi-likelihood methods can be used to incorporate serially correlated and overdispersed covariance structures. These techniques are illustrated using cancer mortality data from selected industrialized countries.

Adolescent↗
PubMed1990

Is brain cancer mortality increasing in industrial countries?

This paper analyzes recent age-specific trends in brain and other central nervous system cancer mortality from 1968 to 1986-1987 in the United States, United Kingdom, Italy, France, and West Germany. It also examines changes in the use of diagnostic confirmation technology in the U.S. SEER program from 1973 to 1987 to estimate the influence of such factors on recent mortality trends. Other sources of error have not been evaluated in this paper. In the United States and Sweden, deaths due to brain and other central nervous system cancer, adjusted to the overall population, are unchanging. However, age-specific analyses of brain and other nervous system cancer in six major industrial countries show markedly different trends at different age groups, with drastic increases in brain tumor rates in the old: rates doubled in persons ages 75 to 84. In the United States, microscopic or radiographic confirmation occurred throughout this time period in 96% of all incident cases of brain and other central nervous system cancers diagnosed before death in the SEER program, with older persons receiving consistently more radiographic tests than younger persons. The use of diagnostic technology may change over time and across populations, but it is not known to what extent it accounts for these increasing trends, which require careful additional study.

Adolescent↗
PubMed1990

Multinational trends in multiple myeloma.

Reported mortality rates from multiple myeloma have been increasing in all industrialized countries in the last 20 years. The rate of increase shows a strong interaction with age: it is slow in persons aged 55 to 59, and increases steadily with increasing age to reach rates of increase in excess of 4% per year in persons 85 years and older. The rate of increase is moderately consistent across sexes and countries. Multiple myeloma is one of the best ascertained cancers, which argues against better ascertainment as the sole cause of the increasing trend. Cohort plots in the United States suggest a parallel shift upward in risk between the birth cohorts of 1870 and 1910, with no evidence of differential effects in the elderly. This suggests a real increase is occurring as a result of some general environmental factors.

Age Factors↗
PubMed1990

The Epstein-Barr virus BZLF1 gene product activates the human immunodeficiency virus type 1 5' long terminal repeat.

The Epstein-Barr virus immediate-early gene product BZLF1 transactivates the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR). The BZLF1 gene product caused an 18-fold increase in beta-galactosidase activity from an HIV-1 LTR lacZ expression vector, whereas the HIV-1 transactivator tat caused a 44-fold increase in beta-galactosidase activity. When cells were transfected with both BZLF1 (pEBV-Z) and tat (pTAT3) expression vectors, as well as HIV-1 LTR lacZ plasmid (pLRON), a 214-fold increase in beta-galactosidase activity was observed. This result suggests a synergistic effect of BZLF1 and tat on HIV-1 LTR-directed lacZ gene expression. Analysis of quantitative BZLF1 and tat requirements for maximal HIV-1 LTR activation indicates that BZLF1 does not reduce the amount of tat required for maximal LTR activation, as would be expected if the BZLF1 synergistic effect was due to increased tat gene expression. Thus, coordinate effects of BZLF1 and tat on the HIV-1 LTR or its transcript are probably responsible for synergistic HIV-1 LTR activation.

DNA-Binding Proteins↗
PubMed1990

Passive smoking, air pollution, and acute respiratory symptoms in a diary study of student nurses.

A cohort of approximately 100 student nurses in Los Angeles was recruited for a diary study of the acute effects of air pollution. Smoking histories and presence of asthma and other allergies were determined by questionnaire. Diaries were completed daily and collected weekly for as long as 3 yr. Air pollution was measured at a monitoring location within 2.5 miles of the school. Incidence and duration of a symptom were modeled separately. Pack-years of cigarettes were predictive of the number of episodes of coughing (p less than 0.0001) and of bringing up phlegm (p less than 0.0001). Current smoking, rather than cumulative smoking, was a better predictor of the duration of a phlegm episode (p less than 0.0001). Controlling for personal smoking, a smoking roommate increased the risk of an episode of phlegm (odds ratio [OR] = 1.41, p less than 0.001), but not of cough. Excluding asthmatics (who may be medicated), increased the odds ratio for passive smoking to 1.76 (p less than 0.0001). In logistic regression models controlling for temperature and serial correlation between days, an increase of 1 SD in carbon monoxide exposure (6.5 ppm) was associated with increased risk of headache (OR = 1.09, p less than 0.001), photochemical oxidants (7.4 pphm) were associated with increased risk of chest discomfort (OR = 1.17, p less than 0.001) and eye irritation (OR = 1.20 p less than 0.001), and nitrogen dioxide (9.1 pphm) was associated with increased risk of phlegm (OR = 1.08 p less than 0.01), sore throats (OR = 1.26, p less than 0.001), and eye irritation (OR = 1.16, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1990

Predictors of asthma and persistent wheeze in a national sample of children in the United States. Association with social class, perinatal events, and race.

This study analyzes data from the Second National Health and Nutritional Examination Survey to determine whether black children are more likely to have asthma or wheeze, even after adjusting for environmental and socioeconomic exposures. For children 6 months to 11 yr of age, the unadjusted prevalence for asthma was 3.0% among white children and 7.2% among blacks; prevalence of frequent wheeze was 6.2% among whites and 9.3% among blacks. In a logistic regression model including race, age, and sex, the relative odds (RO) of asthma for black children as compared to white children were 2.5 (95% confidence interval [Cl], 1.9 to 3.4). Other predictors of asthma in a stepwise logistic regression included age, sex (boys versus girls, RO = 1.4), younger maternal age (2 standard deviation [SD] drop in age, RO = 1.4), residence in the central city (RO = 1.6), and family income (RO for the lowest versus highest tertile, RO = 1.7). After adjusting for these risk factors, age and sex, black children still had a 1.7 RO (95% Cl, 1.2 to 2.1) of having asthma. Frequent wheeze was associated with race (black versus white, RO = 1.6), sex (boys versus girls, RO = 1.3), birth weight (2 SD deficit in birth weight, RO = 1.4), and triceps skinfold thickness (increase in odds of asthma for 2 SD increase in skinfold, RO = 1.6). The significant effect of maternal age and birth weight after adjusting for other confounding variables suggests that the in utero environment may be an important determinant of asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma↗
PubMed1990

Rapid events in growth hormone action. Induction of c-fos and c-jun transcription in 3T3-F442A preadipocytes.

To investigate early events in GH action, we examined whether GH altered the expression of c-fos and c-jun mRNA in 3T3-F442A cells. The rapid induction of these early response protooncogenes is one of the initial events in stimulation of cell proliferation and differentiation by a variety of growth factors. In 3T3-F442A preadipocytes, which differentiate in response to GH, treatment with GH for 15-30 min transiently increased the expression of c-fos and c-jun mRNA at GH concentrations in the physiological range (10-500 ng/ml). Both genes were superinduced by GH in the presence of cycloheximide. Nuclear run-on experiments indicated that the effect of GH on c-fos and c-jun occurred at the level of gene transcription, indicating that in the 3T3-F442A preadipocytes, GH acts similarly to other growth factors which induce c-fos and c-jun. Chronic preincubation with the phorbol ester phorbol 12-myristate 13-acetate interfered with the induction of c-fos by GH, suggesting that diacylglycerol and protein kinase C are involved in this effect of GH. Insulin-like growth factor-I and insulin were less effective than equimolar concentrations of GH in inducing c-fos expression. Taken together, these findings are consistent with coordinated expression of c-fos and c-jun playing an early role in responses to GH in 3T3-F442A cells.

Adipose Tissue↗
PubMed1990

Determination of numbers of lead-exposed U.S. children by areas of the United States: an integrated summary of a report to the U.S. Congress on childhood lead poisoning.

In response to Congressional mandate and under the aegis of the Federal Agency for Toxic Substances and Disease Registry (ATSDR), a comprehensive report to Congress on childhood lead poisoning in the United States was prepared. We have examined numbers of lead-exposed U.S. children by socioeconomic/demographic strata for children 0.5 to 5 years of age; by children in U.S. lead-screening programs; and by enumerations of children 0.5 to 5 years old in the oldest (i.e., highest paint lead and lead plumbing) housing. Using blood lead (PbB) prevalence projection modeling and data of the Second National Health and Nutrition Examination Surgery (NHANES II), it is estimated for 1984 that 2.4 million black and white children 0.5 to 5 years old in metropolitan U.S. had PbB levels greater than 15 micrograms/dL. For all races and the entire nation, we estimate 3 to 4 million children will have PbB levels greater than 15 micrograms/dL. Inner-city, low-income children have the highest prevalences of PbB levels above this criterion level, but sizable numbers of all strata of children have elevated PbB levels when considering both base populations and prevalences for the specific strata (total of 30 strata). Lead screening programs indicate much lower numbers of exposed children compared to NHANES II-based projections, for various reasons that allow programs to underestimate true prevalences. Analysis of 1980 U.S. Census Bureau housing data for 318 standard metropolitan statistical areas show that 4.4 million children 0.5 to 5 years old live in the oldest U.S. housing (pre-1950). Of these, most are actually in the more affluent socioeconomic strata.

Child, Preschool↗
PubMed1990

Determination of numbers of lead-exposed women of childbearing age and pregnant women: an integrated summary of a report to the U.S. Congress on childhood lead poisoning.

In a Congressionally mandated study carried out under the aegis of the U.S. Agency for Toxic Substances and Disease Registry (ATSDR) and summarized in this article, the authors have provided estimates of the numbers of American women of childbearing age and the numbers of American pregnant women whose lead exposure is sufficiently elevated to pose an intrauterine toxicity risk. Exposures associated with such risk were defined as blood lead (PbB) levels greater than 10, greater than 15, greater than 20, and greater than 25 micrograms/dL. Using PbB prevalence projection techniques based on the Second National Health and Nutrition Examination Survey (NHANES II), we first generated projected 1984 prevalences of these PbB levels in white and black women of childbearing age, ages 15 to 19 and 20 to 44. White women in the two age bands had rates of PbBs greater than 10 micrograms/dL of 9.2 and 9.7%, respectively. For black women, the corresponding rates were 8.2 and 19.7%, respectively. Combining these rates with standard metropolitan statistical areas (SMSAs) based 1980 Census and other population enumerations show, for example, that 4.4 million U.S. women of childbearing age are estimated to have had PbBs greater than 10 micrograms/dL. Pregnant black and white women in U.S. SMSAs are approximately 9% of the U.S. black and white childbearing age total, i.e. 3.6 million out of a 41.3 million SMSA total. Of these, 403,200 pregnant women were estimated to have PbB levels greater than 10 micrograms/dL.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗