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Biomedical subjects

J Schwartz

Publications and source records attributed to J Schwartz.

At least 361 records · Page 20Linked to original sources
PubMed1990

Lead-induced anemia: dose-response relationships and evidence for a threshold.

We conducted a cross-sectional epidemiologic study to assess the association between blood lead level and hematocrit in 579 one to five year-old children living near a primary lead smelter in 1974. Blood lead levels ranged from 0.53 to 7.91 mumol/L (11 to 164 micrograms/dl). To predict hematocrit as a function of blood lead level and age, we derived non-linear regression models and fit percentile curves. We used logistic regression to predict the probability of hematocrit values less than 35 per cent. We found a strong non-linear, dose-response relationship between blood lead level and hematocrit. This relationship was influenced by age, but (in this age group) not by sex; the effect was strongest in youngest children. In one year-olds, the age group most severely affected, the risk of an hematocrit value below 35 percent was 2 percent above background at blood lead levels between 0.97 and 1.88 mumol/L (20 and 39 micrograms/dl), 18 percent above background at lead levels of 1.93 to 2.85 mumol/L (40 to 59 micrograms/dl), and 40 percent above background at lead levels of 2.9 mumol/L (60 micrograms/dl) and greater; background was defined as a blood lead level below 1.88 mumol/L (20 micrograms/dl). This effect appeared independent of iron deficiency. These findings suggest that blood lead levels close to the currently recommended limit value of 1.21 mumol/L (25 micrograms/dl) are associated with dose-related depression of hematocrit in young children.

Air Pollutants, Occupational↗
PubMed1990

The use of single sample clearance estimates to probe hepatic drug metabolism: handprinting the influence of cigarette smoking on human hepatic drug metabolism.

1. Conditions were examined under which estimates of drug clearance made from a single measurement of plasma concentration effectively represented multiple-sample estimates of clearance for quinidine, valproic acid, unbound valproic acid, and lorazepam. When plasma concentrations were measured at various post-dose times, both individual and mean values of single-sample clearance estimates, CL, corresponded closely to multiple-sample clearance estimates. Best post-dose sampling times were: quinidine, 8 h; valproic acid, 24 h; and lorazepam, 24 h. 2. Single-sample clearance estimates, CL, were calculated for seven drugs employed as probes of human hepatic drug-metabolizing enzymes. Valproic acid was used to probe microsomal and peroxisomal beta-oxidase activity; antipyrine, phenytoin, quinidine, carbamazepine, and theophylline were used as probes of hepatic mixed-function oxidases (MFO), and lorazepam as a probe for UDP-glucuronosyltransferase activity. 3. A clearance index (CI, namely probe CL for smokers divided by probe CL for non-smokers) was calculated for each probe. The effect of cigarette smoking (and presumably polycyclic aromatic hydrocarbon exposure) on all probe CL values was consolidated and plotted as the logarithm of the CI to produce a handprint of drug metabolizing enzyme activity for cigarette smokers. 4. Only theophylline CL was significantly faster among smokers than non-smokers (P less than 0.01). 5. We conclude that the use of multiple probes of MFO activity when given in a single-dose, single-sample protocol for structuring handprints represents a minimally invasive and useful approach to characterize xenobiotic-mediated effects on hepatic MFO.

Antipyrine↗
PubMed1990

Serum-beta-N-acetyl hexosaminidase (beta-NAH) in the elderly.

Serum levels of beta-N-Acetyl Hexosaminidase (beta-NAH) provide information on the normal non-phagocytic function of Kupffer cells in the liver. Beta-NAH can thus be used as an indicator for non-parenchymal non-phagocytic liver cell function, whereas most of the more routine liver function tests measure hepatocytic status or function. Serum beta-NAH activity levels found in 49 patients and 10 healthy individuals above the age of 65 did not differ significantly from those found in younger controls. The results clearly indicate that beta-NAH serum activity in the aged is within normal limits and, if accepted as a routine measure of the non-phagocytic function of non-parenchymal liver cells, could be used in all adults.

Aged↗
PubMed1990

[Asymptomatic urinary infections in children].

Asymptomatic urinary tract infection is diagnosed on the usual criterion used for urinary tract infections in children (at least 10(5) organisms per ml). There are no clinical manifestations. These asymptomatic infections are due to organisms with little infective potential and no harmful effects on the urinary tract or renal parenchyma. In patients with no malformations of the urinary tract, antimicrobial treatment is unnecessary.

Bacteria↗
PubMed1989

Unusual composition of peptidoglycan in Bordetella pertussis.

The composition of the peptidoglycan of Bordetella pertussis and the nature of its turnover products was determined by a new combination of analytical techniques: high performance liquid chromatography of an enzymatic peptidoglycan hydrolysate and fast atom bombardment mass spectrometry and fast atom bombardment collision-activated dissociation tandem mass spectrometry. Sixteen major components of the peptidoglycan were purified, and assignment of complete or partial chemical structures was achieved for nine and seven species, respectively. At this level of resolution, a previously unrecognized heterogeneity of monomeric (five new species; nine total) and dimeric species (five new species; five total) was detected. No species containing diaminopimelyl-diaminopimelic acid cross-links or lysyl-arginine substitutions were found. Previous estimates of total cross-linkage and average chain length were revised downward to 32% and 21 disaccharide residues, respectively. Detection of a chemically novel species, a disaccharide octapeptide monomer, in both the peptidoglycan hydrolysate and culture supernatant fluid, suggests that an N-acetyl-muramyl-L-alanine amidase acts on the intact peptidoglycan of Bordetella and participates in cell wall turnover. Five peptidoglycan turnover products were identified in the supernatant fluid of late logarithmic phase cultures, including the 1,6-anhydro monomeric species known as tracheal cytotoxin. Peptidoglycan turnover was detected at a low rate of approximately 10%/generation, a value sufficient to account for the generation of all tracheal cytotoxin found in culture supernatant fluids.

Bordetella pertussis↗
PubMed1989

Fluorescent and cytotoxic analogs of corticotropin-releasing factor: probes for studying target cells in heterogeneous populations.

The procedures briefly outlined above described the syntheses of two conjugates of CRF. In each case a molecule with a specific biochemical or physical property was conjugated to an analog of CRF to enable association of the particular property with only CRF-target cells. Thus, by conjugating gelonin or fluorescein to CRF it becomes possible to selectively impair the cellular function of, or fluorescently label, CRF-target cells among mixed populations. These methodologies are still in the early stages of development, and it can be expected that they will become more refined and improved as workers with specialized experience (in synthetic methods, microscopy, cell culture, etc.) continue this work.

Animals↗
PubMed1989

Lung function and chronic exposure to air pollution: a cross-sectional analysis of NHANES II.

The effect of air pollution on lung function in children and youths ages 6-24 years was examined, after controlling for age, height, race, sex, body mass, cigarette smoking, and respiratory symptoms. Forced vital capacity (FVC), forced expiratory volume at 1 sec (FEV1), and peak expiratory flow all showed statistically significant (P less than 0.05) negative correlations with annual concentrations of total suspended particulates (TSP), nitrogen dioxide, and ozone. The ozone and NO2 relationships were highly significant. The TSP relationship was less significant. No relationship was found with sulfur dioxide. The relationships held whether or not children with respiratory conditions, or smokers were included. Demographic and geographic variables had little or no impact on the pollution relationships, which also held when only persons still residing in their state of birth were considered. Essentially identical relationships were found using pollution averaged over 2 years. The relationships held across most NO2 concentrations, but were only apparent at high particulate and ozone concentrations.

Adolescent↗
PubMed1989

New 1,4-dihydropyridine derivatives combining calcium antagonism and alpha-adrenolytic properties.

A series of twelve 1,4-dihydropyridine derivatives incorporating an alpha-adrenergic moiety in one of the ester chains was synthesized. The compounds were evaluated for their calcium antagonist activities by the inhibition of [3H]nitrendipine binding and, in vitro, on pig coronary artery. Their alpha 1- and alpha 2-adrenolytic effects were assessed from their inhibition of [3H]prazosin and [3H]yohimbine binding and, in vitro, on rat aorta and guinea pig vas deferens. Compounds 6 and 9-11 displayed strong calcium antagonist activities, identical with that of nicardipine. The moderate alpha-adrenolytic properties observed were attributed to the presence of alpha-adrenergic moieties. The four chiral derivatives 6a (R,R), 6b (S,S), 6c (S,R), and 6d (R,S) with an N-methyl-N-(benzodioxanylmethyl)amino group on the ester chain were prepared and tested as done previously. Some structure-activity relationships are discussed.

Animals↗
PubMed1989

Regression of experimental cancer by oral administration of combined alpha-tocopherol and beta-carotene.

alpha-Tocopherol (vitamin E) and beta-carotene have been shown to be capable of regressing established epidermoid carcinomas of hamster buccal pouch when injected locally into the tumor site. Neither has yet been shown to be effective in regressing cancer when administered by oral route. However, a combination of both alpha-tocopherol and beta-carotene was shown to be effective in regressing epidermoid carcinomas of hamster buccal pouch when the mixture was administered orally in vegetable oil. The epidermoid carcinomas were induced in the right buccal pouch of 100 Syrian hamsters by painting three times weekly for 14 weeks with a 0.5% solution of 7,12-dimethylbenz[a]anthracene in mineral oil. The animals were then divided into five equal groups of 20 animals. Group 1 animals received no further treatment and represented tumor controls. Group 2 animals received 200 micrograms beta-carotene and 200 micrograms dl-alpha-tocopherol acid succinate combined in 0.2 ml vegetable oil. Animals received the mixture daily by mouth using a 1-ml syringe. Groups 3 and 4 received beta-carotene and alpha-tocopherol individually in double amounts (400 micrograms in 0.2 ml vegetable oil). Group 5 animals received only the vegetable oil (0.2 ml daily) and were controls for vehicle. The animals in Groups 1, 3, 4, and 5 were killed after 22 weeks because the tumors were extensive, large, and necrotic and the animals were weak and cachectic. After 22 weeks, the tumors in Group 2 animals were small in 15 out of 20 animals. The tumors were reduced in size compared with tumor burden at 14 weeks, the point at which the beta-carotene/alpha-tocopherol was started.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1989

Posttraumatic stress disorder as a consequence of the POW experience.

To estimate the relative contributions of trauma and premorbid disposition in the development and persistence of posttraumatic stress disorder (PTSD) symptoms, we conducted structured psychiatric interviews of 62 former World War II POWs. Half these men satisfied DSM-III criteria for PTSD in the year following repatriation. Eighteen (29%) continued to meet the criteria for PTSD 40 years later. Family history of mental illness and preexisting psychopathology were at best only weakly correlated with persistent PTSD symptoms. The strongest predictors of PTSD were proportion of body weight lost and the experience of torture during captivity. This study demonstrates that former POWs frequently develop posttraumatic stress disorder and that for one half of those who develop the symptoms, they persist for over 40 years. Familial risk factors and preexisting psychopathology are superseded by the overwhelming nature of the trauma. The persistence of the symptoms for many years is a reflection of the severity of the trauma.

Aged↗
PubMed1989

Intrapituitary cell-cell communication regulates ACTH secretion.

Exposure of rat anterior pituitary cells in culture to a cytotoxin specific for CRF-target cells is followed by increased basal ACTH secretion from the remaining cells three days after the last exposure to the cytotoxin. When CRF-target-depleted populations are co-cultured with unexposed pituitary cells ACTH secretion is more than double that predicted in the absence of cell-to-cell interaction. These data provide evidence for an intrapituitary cell-to-cell signalling system modulating ACTH secretion.

Adrenocorticotropic Hormone↗
PubMed1989

Improved radioreceptor assay for the determination of plasma levels of dihydropyridine calcium channel blockers in humans.

Ways of improving sensitivity of the radioreceptor assay to determine the plasma levels of dihydropyridine calcium antagonists were investigated. Extraction of the drug from plasma with organic solvent was found to enhance the sensitivity of the assay (method 1). Alternatively, the inhibitory effect observed when plasma is added directly to the binding assay can be counteracted by increasing the amount of membranes in the assay (method 2). Plasma levels after single oral doses of nitrendipine and nicardipine were followed with method 1. Plasma levels of isradipine were measured with methods 1 and 2 and by mass fragmentography. The data confirm that nitrendipine plasma level kinetics vary widely from patient to patient, whereas for nicardipine the drug level profile is more homogeneous. The similarity of the data obtained from the radioreceptor assay and from mass fragmentography suggests the absence of any active metabolite of isradipine.

Animals↗
PubMed1989

An attempt to prevent or delay denervation changes in rat muscles.

A number of drugs which are known to affect lysosomes and their enzyme activities were used in an attempt to inhibit or delay the onset of denervation changes in rat muscles. The following parameters were used: the occurrence of fibrillations in electromyographs; diameters of muscle fibers; acid phosphatase activity; acetylcholinesterase activity and distribution in end plates. Differences between denervated and non-denervated limbs were evaluated and compared in the different treatment groups. The various parameters were differently affected by the different drugs. Chloroquin, thiouracil and streptomycin appeared to be more effective than other treatments in the inhibition of denervation changes.

Animals↗
PubMed1988

Purification and properties of a novel recombinant human hybrid interferon, delta-4 alpha 2/alpha 1.

The human interferon (huIFN) delta-4 alpha 2(5-62)/alpha 1(64-166) is a genetically engineered hybrid that consists of residues 5-62 of huIFN alpha 2 and residues 64-166 of huIFN alpha 1. This variant contains four cysteine residues at positions 29, 86, 99 and 139, but does not contain the cysteine at position 1 that is characteristic of naturally occurring huIFN alpha subtypes. This novel recombinant hybrid was purified from Escherichia coli to greater than 95% homogeneity. The purification was based on ethanol extraction of a trichloroacetic acid precipitate and Matrex Gel Blue A chromatography followed by either a selective precipitation or DEAE-Sepharose chromatography. The purified protein that was treated with 2-mercaptoethanol exhibited two closely migrating bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with apparent molecular weight values of 17,800 and 17,100, both of which exhibited antiviral activity. Electrophoresis performed without prior reduction with 2-mercaptoethanol indicated only a minor extent of intermolecular disulfide bonding. The purified protein exhibited a high specific antiviral activity of 7 x 10(7) units/mg when assayed on human fibroblast cells and, in distinction to the parental huIFN alpha 2, it also demonstrated antiviral activity on human fibroblast cells and, in distinction to the parental huIFN alpha 2, it also demonstrated antiviral activity on murine L929 cells. The level of antiproliferative activity of huIFN delta-4 alpha 2(5-62)/alpha 1(64-166) on various cell lines of different histological origin appeared to be more comparable to that of huIFN alpha 1 than huIFN alpha 2. The data suggest that huIFN delta-4 alpha 2(5-62)/alpha 1(64-166) hybrid may be a useful tool for understanding huIFN structure-function relations.

Antiviral Agents↗