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Biomedical subjects

B D Goldstein

Publications and source records attributed to B D Goldstein.

At least 19 recordsLinked to original sources
PubMed1992

The role of GABA and glycine in the physostigmine-induced alterations of spinal cord reflexes.

The purpose of this study was to determine which inhibitory pathway(s) mediate the alterations in the monosynaptic (MSR) and polysynaptic (PSR) reflexes after two different doses of physostigmine. It was found previously that 0.8 mg/kg physostigmine facilitated the MSR and 2.0 mg/kg initially depressed and then facilitated the MSR. Both doses facilitated the PSR. In this study, the animals were pretreated with either strychnine (0.1 mg/kg) or bicuculline (0.5 mg/kg), prior to the administration of either dose of physostigmine. It was found that both strychnine and bicuculline blocked the facilitation produced by the small dose of physostigmine, while bicuculline alone blocked the depression of the MSR produced by the large dose of physostigmine. Strychnine partially blocked the effects of both doses of physostigmine on the PSR, while bicuculline only partially blocked the effects of the small dose of physostigmine. These data suggest that the depression of the MSR was the result of a GABA-mediated pathway, while the facilitation of MSR involved both glycine and GABA.

Animals↗
PubMed1992

Risk to groundlings of death due to airplane accidents: a risk communication tool.

During the period 1975-85 in the United States the 70 year lifetime risk of dying from being hit by an airplane when the individual is on the ground was 4.2 per million people. In contrast to many other risks used for comparison purposes, risk to those on the ground from an airplane crash is not a function of our own skills; is not optional; provides no benefit to anyone involved; and is not an act of nature. As a risk comparison tool it also has the useful characteristics of being something about which we can agree that regulatory action, such as control of airplane use and traffic, is warranted; but that no significant change in personal behavior, such as living in the basement to protect against dying from a plane hitting the home, is commensurate with the extent of risk.

Accidents, Aviation↗
PubMed1991

Release of substance P into the superficial dorsal horn following nociceptive activation of the hindpaw of the rat.

Substance P (SP) has been widely proposed as being involved in the transmission of nociceptive information in the dorsal horn of the spinal cord. Formalin injected into the hindpaw as a nociceptive stimulus has been shown to increase the amount of immunoreactive SP in the dorsal horn, perhaps by decreasing SP release from primary afferent neurons. Much is known concerning the release of SP from tissue slices or from the entire spinal cord in vivo. However, less is known about the release patterns of SP in the superficial dorsal horn during the activation of peripheral nociceptors. In this study, noxious pinch applied to and formalin injection into the hindpaw were used as nociceptive stimuli while a stereotaxic push-pull cannula was used to perfuse the L5 dorsal horn. Experiments were conducted in unanesthetized decerebrate/spinal rats, and radioimmunoassay was used to determine the SP-like immunoreactivity (SPLI) content of collected perfusates. Results demonstrate that graded intensities of noxious mechanical pinch produced progressively increased release of SPLI into the dorsal horn; SPLI release returned to baseline rates following termination of the stimulus. The injection of 100 microliters of 5% formalin into the hindpaw produced a biphasic inhibition of SPLI release 0-40 min and greater than 60 min after formalin injection. The application of a noxious pinch following formalin injection produced an increase in SPLI release which did not return to baseline rates; this may be indicative of production of a hyperalgesic state caused by formalin injection. The results of this study support the concept that formalin injected into the hindpaw activates segmental antinociceptive systems which block SP release and limit nociceptive transmission.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Depression of iron uptake into erythrocytes in mice by treatment with the combined benzene metabolites p-benzoquinone, muconaldehyde and hydroquinone.

Using radio-iron uptake into erythrocytes as a measure of hematopoiesis, it was demonstrated that p-benzoquinone (BQ) and muconaldehyde (MUC) are potent inhibitors of bone marrow function in female mice. These two benzene metabolites reduced iron uptake at dosages of less than 5-6 mg kg-1. The combination of MUC and hydroquinone (HQ) (100 mg kg-1) was additive, reducing iron incorporation to an extent that was the sum of the effect of each chemical given alone. The combined effect of MUC and BQ was significantly less than additive, demonstrating antagonism in the response. Multiple regression was used to study the contributions of the components of binary mixtures of the benzene metabolites (METAB). Data obtained from standard curves of METAB and their mixtures are separable in regression analysis. Thus, for zero interaction of METAB, the responses would be simply additive, while positive and negative interaction would indicate synergy and antagonism, respectively. T-testing of the data resulted in non-significant values for the mixture MUC + HQ, indicating zero interaction and an additive response. The negative t-values obtained for the mixture MUC + BQ, however, indicate negative interaction or an antagonistic response. Since mutually exclusive agents share the same binding sites and occupation of a site by one agent excludes its occupation by another, they cannot interact in producing the effect; combinations of these agents show zero interaction and are simply additive. This suggests that HQ and MUC are mutually exclusive and share the same binding site.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehydes↗
PubMed1991

Effects of acute administration of soman on spinal cord reflexes in the cat.

The acute effects of the organophosphorus acetylcholinesterase inhibitor, soman, was studied on spinal cord reflexes in the spinal cord transected cat. It was found that doses of 10 micrograms/kg significantly altered the monosynaptic and dorsal root reflexes by causing an initial depression lasting about 20 min followed by a later facilitation lasting over 3 h. A higher dose of soman (20 micrograms/kg) caused the initial depression but did not produce the later facilitation. Cholinergic antagonists were used to determine whether these changes were related to inhibition of acetylcholinesterase or whether they were non-specific. It was found that mecamylamine blocked the depression and the facilitation while atropine depressed the spinal cord potentials. These data show that acute administration of 10 micrograms/kg soman produces specific effects on spinal cord reflexes which could be characterized as resulting from inhibition of acetylcholinesterase similar to the carbamate inhibitor, physostigmine.

Animals↗
PubMed1991

Epidemiologic investigation of a cancer cluster in professional football players.

In 1976, the New York Giants professional football team relocated to the newly constructed Meadowlands Sports Complex (MSC) in East Rutherford, NJ. Between 1980 and 1987 four team members developed cancer: one case each of non-Hodgkin's lymphoma, glioblastoma, angiosarcoma, and Hodgkin's disease. Because the surrounding area contains three superfund sites, concern was widespread that the cancers were related to environmental contamination. To assess for a possible environmental etiology, we conducted clinical, environmental, and epidemiologic studies at the MSC. Measurements of volatile organic compounds were all below occupational exposure limits and were similar to ambient levels in nearby Lyndhurst, NJ. Outdoor AM radio broadcast field strengths were in the uppermost 0.1% of field strengths measured in urban areas of the United States. Proportionate mortality ratio and proportional cancer incidence ratio studies of the MSC workforce found no excesses of cancer deaths or of incident cancer cases either for all sites combined or for any specific site. No significant differences in cancer incidence or mortality were found between indoor and nonindoor workers. Based on examination of all available data, the four cancer cases were judged most likely to have been clustered by chance and not to have been caused by environmental conditions at the MSC.

Adult↗
PubMed1991

Soft plastic bread packaging: lead content and reuse by families.

The presence of lead in labels painted on soft plastic bread packaging was evaluated. Lead was detected on the outside of 17 of 18 soft plastic bread bags that were analyzed, with an average of 26 +/- 6 mg per bag with lead. Of 106 families questioned, 16 percent of respondents reported turning the bags inside out before reusing for food storage, thus putting food in contact with the lead paint. We estimate that a weak acid, such as vinegar, could readily leach 100 micrograms of lead from a painted plastic bag within 10 minutes. Further, lead and other metals painted on food packaging of any type becomes part of the municipal waste stream subject to incineration and to land-filling. The use of lead in packaging presents an unnecessary risk to public health.

Bread↗
PubMed1990

Changes of substance P-like immunoreactivity in the dorsal horn are associated with the 'phasic' behavioral response to a formalin stimulus.

Substance P (SP) has been proposed as a nociceptive transmitter/modulator in the dorsal horn of the spinal cord. Formalin used as a nociceptive stimulus has been shown to increase, in a biphasic manner, the amount of immunoreactive SP in the dorsal horn. The time course of the changes in substance P-like immunoreactivity (SPLI) caused by formalin is similar to both the electrical activity of dorsal horn neurons and licking behaviors. The administration of morphine reduces stereotypic behaviors caused by a formalin injection but actually increases the amount of SPLI in the dorsal horn. Therefore, the extent to which SP in the dorsal horn is involved with nociception as a result of formalin remains uncertain. To test the involvement of SP with chemogenic nociception, we utilized lidocaine to block afferent activity prior to an injection of formalin and studied the time course of behaviors and SPLI changes in the dorsal horn. Our results showed that formalin produced two distinct phases of nociceptive behaviors as measured by stereotypic licking of the injected paw: an acute 'phasic' response followed by a longer-lasting 'subacute' or 'tonic' response. Lidocaine reduced both phases of stereotypic behaviors, but only reduced the first increase of SPLI in the dorsal horn. These results suggested a direct involvement of SPLI in the dorsal horn with only 'phasic' behavioral responses to a formalin stimulus.

Animals↗
PubMed1990

Comparative metabolism of benzene and trans,trans-muconaldehyde to trans,trans-muconic acid in DBA/2N and C57BL/6 mice.

Our laboratory recently identified trans,trans-muconaldehyde (MUC), a six-carbon diene dialdehyde, as a hematotoxic microsomal metabolite of benzene (Latriano et al., Proc Natl Acad Sci USA 83: 8356-8360, 1986). We also showed that MUC is metabolized in vitro to trans,trans-muconic acid (MA), a six-carbon diene dicarboxylic acid and known urinary metabolite of benzene. To elucidate further the role of ring-opened metabolites in benzene toxicity, the metabolism of benzene and MUC was examined in the benzene sensitive DBA/2N mouse strain and the less benzene sensitive C57BL/6 strain. A sensitive assay for urinary MA analysis was developed. The percent of benzene dose excreted as urinary MA within the first 24 hr after treatment decreased with an increase in benzene dose, i.e. from 9.8 to 0.4% in DBA/2N mice and from 17.6 to 0.2% in C57BL/6 mice treated with 0.5 to 880 mg/kg benzene. DBA/2N mice excreted significantly (P less than or equal to 0.05) more MA compared with C57BL/6 mice after treatment with hematotoxic benzene doses (220-880 mg/kg). At low benzene doses (0.5 to 2.5 mg/kg), C57BL/6 mice excreted significantly (P less than or equal to 0.05) more MA compared with DBA/2N mice. There were no significant differences in the metabolism of MUC to MA between the two strains after treatment with 0.5 to 3.0 mg/kg. Furthermore, mice from both strains excreted similar amounts of muconic acid when treated with 0.7 to 7.1 mg/kg MA. These results are consistent with the hypothesis that reactive ring-opened metabolites such as trans,trans-muconaldehyde play a role in benzene hematotoxicity. Sensitivity towards benzene may be due, in part, to increased metabolism to ring-opened compounds.

Aldehydes↗
PubMed1990

Lack of evidence for the size principle of selective vulnerability of axons in toxic neuropathies. I. The effects of subcutaneous injections of 2,5-hexanedione on behavior and muscle spindle function.

2,5-Hexanedione (HD) produces a central-peripheral distal axonopathy. It has been suggested that agents which produce this type of axonopathy show a predilection to the largest diameter fibers. This has been based primarily on morphological data. However, electrophysiological evidence and some clinical and morphological data suggest that this may not be the case. In particular, in acrylamide neuropathy, muscle spindle primary afferents do not show this selectivity, as well as autonomic fibers. This study was carried out to determine whether the largest diameter axons were selectively vulnerable to HD. We found that subcutaneous injections of HD in cats produced a dose-dependent increase in behavioral deficits such as contact placing, stepping, and locomotion. There was also a dose-dependent decrease in the position sensitivity of muscle spindle primary and secondary endings. However, the secondary endings, which are innervated by smaller axons, were affected prior to the primary endings. Also, the velocity sensitivity of the primary endings was depressed at a similar time frame as the position sensitivity of these same endings. These data are consistent with the hypothesis that the caliber of the axon is not the only determinant of the selective vulnerability of axons in distal axonopathy.

Animals↗
PubMed1990

Effects of 2,5-hexanedione on deefferented muscle spindle position sensitivity.

2,5-Hexanedione (HD) produces a neurofilamentous axonpathy in humans and experimental animals. The present study was carried out to determine the time course of the effects of HD on muscle spindle position sensitivity to permit comparisons with similar effects of other toxicants which produce a neurofilamentous axonopathy. Cats were administered HD either via their drinking water or via osmotic minipumps. Muscle spindle position sensitivity was tested after a total HD dose of 2.43 or 4.85 g/kg via the drinking water or 0.96, 1.91, or 4.78 g/kg via an osmotic minipump. The position sensitivities of both primary and secondary endings were depressed regardless of the route of administration. However, secondary muscle spindle afferents in the animals intoxicated with HD via the minipumps were affected to a greater extent than primary muscle spindle afferents at all doses studied. These data show that HD alters muscle spindle function and lends support to the suggestion that the largest diameter fibers are not the most vulnerable to HD.

Analysis of Variance↗
PubMed1990

Genetic toxicity of the benzene metabolite trans, trans-muconaldehyde in mammalian and bacterial cells.

Previous studies in our laboratory identified trans,trans-muconaldehyde (MUC), a six-carbon diene dialdehyde, as a microsomal metabolite of benzene. This ring-opened metabolite of benzene was also shown to be hematotoxic in mice in a manner similar to benzene. To further explore the role of MUC in relation to benzene toxicity, a number of test systems were utilized to determine its genotoxic potential. In B6C3F1 mice, MUC induced a highly significant increase in sister-chromatid exchange (SCE), the lowest effective dose being 3 mg/kg, but failed to induce any micronuclei (MN). In Chinese hamster ovary (CHO) cells, MUC at concentrations up to 0.8 micrograms/ml was negative in the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) assay. Dose-related increases in the percentage of cells with MN were observed in CHO cells treated with 0.4-0.8 micrograms/ml MUC. MUC did not-cause unscheduled DNA synthesis in rat primary hepatocytes. Treatment of Salmonella typhimurium TA97 with MUC induced a low level of mutations at concentrations ranging from 10 to 70 micrograms/ml with or without S9 activation. MUC was inactive in strains TA1535, TA100, TA1538 and TA98. In CHO cells and rat primary hepatocytes, MUC was cytotoxic at 0.4 and 4.0 micrograms/ml, respectively. Concentrations of 100 micrograms/plate MUC were toxic for bacterial cells. The present findings indicate that MUC is nonmutagenic or minimally mutagenic in bacterial and mammalian in vitro systems. In mammalian cells, MUC is highly cytotoxic and genotoxic.

Aldehydes↗
PubMed1990

Role of the physician in environmental medicine.

This article describes the role of the medical history and of laboratory findings in diagnosing diseases caused by environmental chemicals. An understanding of routes of exposure is crucial in appropriate diagnosis and in preventing further harm. A listing of potential sources of information is also included.

Environmental Health↗