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Biomedical subjects

B D Goldstein

Publications and source records attributed to B D Goldstein.

At least 91 records · Page 5Linked to original sources
PubMed1988

Hematologic effects of benzene: a thirty-five year longitudinal study of rubber workers.

We studied over 17,000 peripheral blood counts, accumulated during surveillance from 1940 through 1975, from a cohort of 459 benzene-exposed workers. Linear regressions demonstrated significant decreases in white and red cell counts, as well as hemoglobin, for workers exposed during the 1940's, without persistent trends over the ensuing 25 years. Strongly positive correlations were observed between these blood count fluctuations and fluctuations in retrospective estimates of benzene exposures for this plant for the earlier periods of surveillance (mean estimated exposure 1940 to 1948, 75 ppm), but not for later years (mean estimated exposure 1948 to 1975, 15 to 20 ppm). These data suggest substantial limitations of hematologic examination of populations to detect abnormalities in populations currently exposed to benzene. The data also demonstrate a novel approach to the biological validation of exposure estimates based upon limited industrial hygiene and historical record data.

Benzene↗
PubMed1988

Prolonged red blood cell glycerol hemolysis in mice inhaling benzene.

Inhalation of benzene produces a prolongation of mouse red blood cell glycerol hemolysis time. This was not observed in red blood cells directly incubated in benzene. Increased resistance to the hemolytic action of glycerol should be explored as a potentially useful biological monitoring procedure in the red blood cells of benzene-exposed humans.

Animals↗
PubMed1987

Inhibition by reactive aldehydes of superoxide anion radical production from stimulated polymorphonuclear leukocytes and pulmonary alveolar macrophages. Effects on cellular sulfhydryl groups and NADPH oxidase activity.

Alpha,beta-unsaturated aldehydes such as acrolein (ACR) and crotonaldehyde (CRO) have been shown previously in our laboratory to inhibit the production of superoxide anion radical (O2-) by stimulated phagocytic cells in vitro in a dose-related manner. Based on the known reactivity of these compounds towards cellular sulfhydryls (SH), the present studies were aimed at investigating cellular SH status in relation to O2- production. Plasma membrane surface SH groups were measured using carboxypyridinedisulfide and monitoring the resultant formation of mixed disulfides through assay of thione released into the supernatant fraction. Intracellular non-protein sulfhydryls were measured using 5,5'-dithiobis-2-nitrobenzoic acid. In both human polymorphonuclear leukocytes (PMN) and rat pulmonary alveolar macrophages (PAM) there was a dose-related decrease in surface SH and soluble SH after ACR and CRO treatment. Propionaldehyde, a three-carbon saturated aldehyde, was without effect. The decrease in surface SH was greater than the decrease in soluble SH. In addition, in PMN and PAM preincubated with 5-40 microM ACR, there was a dose-related inhibition in the rate of O2- production with no effect on the lag time as measured by cytochrome c reduction. In stimulated PMN, there was a dose-related decrease in the rate after addition of 5-40 microM ACR. These data suggest that changes in SH status by reactive aldehydes can modulate the activity of the plasma membrane NADPH oxidase responsible for O2- production.

Aldehydes↗
PubMed1987

Primary afferent terminal function following acrylamide: alterations in the dorsal root potential and reflex.

The dorsal root potential (DRP) and the dorsal root reflex (DRR) were studied in acrylamide (ACR)-induced axonopathy to determine the nature and extent of primary afferent terminal (PAT) dysfunction. Cats were administered 30 mg/kg/day ACR for either 5 (ACR 5D) or 10 (ACR 10D) days. The day after the last injection, the spinal cord as isolated in situ and the DRP and DRR were elicited. It was found that only 21% of the ACR 10D animals exhibited a DRP. Furthermore, in that 21%, the DRP appeared to degrade over distance differently from the control group. There was no change in the DRP evoked in the ACR 5D group. ACR affected the DRR when evoked from the cutaneous sural nerve (SU) to a greater extent than when evoked from the medial gastrocnemius (MG) nerve. A SU-evoked DRR could not be elicited in any of the animals in the ACR 10D group and in only 20% of the ACR 5D group. There was no difference in the ability to elicit a MG-evoked DDR in either ACR-treated group when compared to control. However, the maximum-evoked area under the DRR elicited from the MG nerve was significantly smaller in the ACR-treated groups than in control. These data show that ACR does indeed impair PAT function. ACR preferentially affects the PAT processing of the SU when compared to the MG nerve, which may indicate that the selective vulnerability of the largest diameter fibers to ACR is not necessarily true.

Acrylamide↗
PubMed1987

Electrophysiological changes in the primary sensory neuron following subchronic soman and sarin: alterations in sensory receptor function.

Cats were administered soman or sarin either in a single high dose (1 mg/kg) with pretreatment or in multiple sublethal doses to determine whether these potent organophosphorus agents could produce a delayed neurotoxicity and what, if any, pathophysiological changes occurred in peripheral sensory receptors. Neither soman nor sarin, when administered as a single high dose, produced a delayed neurotoxicity as observed behaviorally for up to 60 days. There were also no observable signs of delayed neurotoxicity when these agents were administered in multiple doses. Functional tests of proprioceptors and mechanoreceptors were performed on the cats which received multiple sublethal doses of either soman or sarin. It was found that the discharge rates of muscle spindle primary endings were depressed while the discharge rates of secondary endings were facilitated following the administration of either soman or sarin. The discharge rates of slowly adapting type 1 mechanoreceptors were also depressed. The total number of identified mechanoreceptors was reduced in both the soman- and sarin-treated animals. Conduction velocities of several of the muscle spindle and mechanoreceptor afferents were significantly decreased. The alterations in muscle spindle function may be due to changes in the muscle resulting from acetylcholinesterase inhibition. Another explanation for the changes in both muscle spindle and mechanoreceptor function may be the direct effect of the organophosphorus agents on the afferents themselves, thus altering their excitability.

Animals↗
PubMed1987

Alteration of erythrocyte membrane fluidity by heavy metal cations.

Fluorescence polarization measurements were carried out on erythrocyte ghosts treated with heavy metal cations. Membranes labelled with the fluorescent lipid probe all-trans 1,6-diphenyl-1,3, 5-hexatriene (DPH) had increased DPH polarization (P) values, consistent with increased membrane lipid viscosity, when treated with 10(-3)-10(-2) M of the chloride salts of cadmium, zinc or lead for 1 hour at 37 degrees C, but not with calcium. Using cadmium as a prototype heavy metal, additional studies showed that exposure of ghosts to cadmium also increased the native protein fluorescence polarization. These increases in P values were observed at temperatures ranging from 15-40 degrees C. These data suggest that interaction of cadmium and other heavy metals with cellular membranes may alter membrane lipid and possibly membrane protein fluidity, which may contribute to abnormal cellular function.

Cadmium↗
PubMed1986

Regulatory mechanisms for substance P in the dorsal horn during a nociceptive stimulus: axoplasmic transport vs electrical activity.

Substance P (SP) is believed to be a neuromediator of nociception in the dorsal horn of the spinal cord. SP precursor is synthesized in the dorsal root ganglia (DRG) and transported via axoplasmic transport to the nerve terminal where it is stored and released as SP. The chemical nociceptive stimulus, formalin, when injected into the hindpaw causes an increase in the level of SP in the dorsal horn. This increase in SP may be the result of increased electrical activity due to activation of free nerve endings or the transport of some chemical or trophic signal to the DRG or to the central terminal. This study investigates the mechanism of the SP increase during the formalin stimulus. Rats were anesthetized and a laminectomy performed. In some experiments the sciatic nerve was exposed. Agar gel pads containing either colchicine or tetrodotoxin (TTX) were applied to the dorsal root or sciatic nerve prior to the injection of 5% formalin or saline into the hindpaw. Electrical activity across the dorsal root distal to the gel pad was monitored to determine the effects of colchicine and TTX on the nerve. Sixty min after the injection into the hindpaw, the animal was perfused and the lumbar spinal cord removed. Ten-micron frozen sections were stained for SP. It was found that the formalin-evoked increase in SP could be partially blocked by either colchicine or TTX applied to the dorsal root and completely blocked by the application of both agents together. TTX or colchicine applied to the sciatic nerve completely blocked the formalin-evoked increase in SP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Paradoxical changes in spinal cord reflexes following the acute administration of acrylamide.

Acrylamide (ACR) produces a central-peripheral distal axonopathy when administered chronically. This is characterized functionally by decreases in the monosynaptic reflex (MSR) and dorsal root potential (DRP) and alterations in the characteristics of the dorsal root reflex (DRR). Acute administration of ACR inhibits the oxidative enzyme complex NADH-tetrazolium reductase and slows retrograde axoplasmic transport. This study was carried out to determine if the spinal cord reflexes are also affected following acute administration of ACR. Dose-response studies revealed a dose-dependent increase in both the MSR and DRR. A single injection of 50 mg/kg ACR caused an increase in both the MSR and DRR within 15 min and continued for over 3 h. These data are paradoxical since chronic administration of ACR results in decreased function. Two possible mechanisms are proposed. First, calcium ion regulation may be involved in both the acute and chronic effects of ACR on spinal cord reflexes. Second, a depolarization of the neurons is occurring just prior to cell injury or death.

Acrylamide↗
PubMed1986

The reaction of 2-thiobarbituric acid with biologically active alpha,beta-unsaturated aldehydes.

The standard assay for lipid peroxidation is the measurement of the pink, 532 nm absorbing chromogen which is formed upon reaction of 2-thiobarbituric acid (TBA) with the lipid peroxidation product malonaldehyde (MDA). The present studies indicate that the toxic lipid peroxidation product trans-4-hydroxynonenal and its dehydration product trans,trans-nonadienal react with TBA to form chromogens which absorb maximally at 530 and 532 nm, respectively. Other biologically active alpha,beta-unsaturated aldehydes, such as acrolein and crotonaldehyde, short-chain homologs of alkenals formed during lipid peroxidation, and trans,trans-muconaldehyde, a novel diene dialdehyde, react with TBA to form products which absorb maximally at 495 nm. The molar extinction coefficients of the aldehyde:TBA chromogens formed were found to vary widely, suggesting that only small contributions to the 532 nm absorption by TBA adducts of reactive aldehydes other than MDA may be encountered during the use of the TBA assay.

Aldehydes↗
PubMed1986

Formation of muconaldehyde, an open-ring metabolite of benzene, in mouse liver microsomes: an additional pathway for toxic metabolites.

It has been proposed that a ring-opened form may be responsible for the toxicity of benzene. The present studies demonstrate that incubation of [14C]benzene with liver microsomes (obtained from male CD-1 mice treated with benzene) in the presence of NADPH results in the formation of a ring-opened product. Evidence for the identity of this product was obtained by derivatizing with 2-thiobarbituric acid (TBA), which resulted in the formation of an adduct with a 490-nm absorbance maximum. This maximum is identical to that observed after authentic trans,trans-muconaldehyde has reacted with TBA. Separation of muconaldehyde, both with and without trapping with TBA, from other benzene metabolites in the incubation mixture was accomplished by HPLC. The radioactivity profile of fractions collected during HPLC analysis contained peaks that eluted with muconaldehyde and the muconaldehyde-TBA adduct. The structure of the ring-opened product was confirmed by mass spectrometry, studies in which the HPLC peak from the microsomal incubation mixture that eluted at the retention time of authentic muconaldehyde was collected and derivatized with 2,4-dinitrophenylhydrazine. The high-resolution mass spectrum of this sample contained an ion with an m/z of 291.0729, corresponding to muconaldehyde mono-dinitrophenylhydrazone. These results indicate that benzene is metabolized in vitro to a ring-opened product identified as muconaldehyde.

Aldehydes↗
PubMed1986

Estimation of risk of glucose 6-phosphate dehydrogenase-deficient red cells to ozone and nitrogen dioxide.

It has been suggested that the more than 1 million black Americans with the A- variant of glucose-6-phosphate dehydrogenase deficiency (G6PD) are at risk for adverse hematologic effects due to inhalation of ambient levels of oxidant gases. To evaluate this hypothesis studies were performed that included direct exposure of human G6PD-deficient red cells, and of mouse strains with different G6PD levels, to the oxidant gases ozone and nitrogen dioxide. Using the oxidant drug phenylhydrazine in part as a point of comparison, conservative extrapolation of the data indicates that exposure to levels of ozone or nitrogen dioxide at least one and probably two orders of magnitude above the LD50 would be required for any hematologic effect to be observed of pertinence to G6PD deficiency. It is concluded that there is no reason to remove or preclude from the workplace black employees with the common A- variant of red cell G6PD deficiency who potentially are exposed to oxidant gases.

Animals↗
PubMed1986

Biological and ambient monitoring of benzene in the workplace.

Surveillance of workers potentially exposed to benzene is focused on detecting evidence of bone marrow toxicity. A particularly thorough hematological evaluation should be conducted upon entrance to the work force at risk. This should be followed by semiannual surveillance using the routine complete blood count as the major monitoring technique. Attention should also be placed on increases in the mean corpuscular volume and decreases in the lymphocyte count as possible early indicators of benzene toxicity. Other hematological findings that may indicate early benzene toxicity depend upon alterations in the characteristics of blood cells, eg, a prolongation of the red cell glycerol hemolysis time, need to be more fully evaluated. No single finding or constellation of findings is pathognomonic of benzene hematotoxicity, and all findings must be carefully interpreted in terms of the individual or group at risk.

Air Pollutants, Occupational↗
PubMed1986

Acrylamide produces a direct, dose-dependent and specific inhibition of oxidative metabolism in motoneurons.

The mechanism of action of acrylamide (ACR) in producing a central-peripheral distal axonopathy is unknown. We have tested the hypothesis that ACR inhibition of enzymes of oxidative metabolism is responsible for compromise of the energy supply, thereby producing the neuropathy. A single 50 mg/kg i.p. dose of ACR resulted in a 33.4% decrease in NADH-tetrazolium reductase (NADH-TR) (indicative of oxidative metabolism) activity in rat soleus motoneurons within one hour of injection. Methylene bis ACR (Mb-ACR), a non-neurotoxic analogue, produced a much smaller (6.7%) decrease in NADH-TR activity. Restoration of normal NADH-TR activity following that single injection occurred in 3 days. In vitro histochemical assays demonstrated a dose-dependent inhibition of motoneuron NADH-TR activity (10-54%) by 1-10mM ACR. Equimolar Mb-ACR produced significantly less inhibition. The rapid, dose-dependent and specific inhibition of this oxidative enzyme activity by ACR provides evidence in support of the energy hypothesis of ACR-induced neuropathy and more specifically suggests that oxidative enzyme inhibitions are a critical site of ACR action.

Acrylamide↗
PubMed1985

Short-term toxicity of trans,trans-muconaldehyde.

Toxicological and biochemical effects of muconaldehyde, a six-carbon diene dialdehyde, were evaluated in 6- to 9-week-old CD-1 male mice. The LD50 of trans,trans-muconaldehyde was 6.7 and 7.1 mg/kg body wt when calculated by two different methods. Administration of trans,trans-muconaldehyde (2 mg/kg, ip) daily for 10 and 16 days resulted in a statistically significant decrease in red blood cell count, hematocrit, hemoglobin, bone marrow cellularity, and hepatic total and free sulfhydryl content. There was an increase in white blood cell count and spleen weight at 16 days. Similar effects, but of much lesser magnitude, were observed when the mice were given the same total dose of 2 mg/kg divided into three daily ip injections of 0.67 mg/kg trans,trans-muconaldehyde for 10 and 16 days. This alpha,beta-unsaturated aldehyde is a potent bone marrow toxin in mice.

Aldehydes↗