Cancer and the environment.
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Biomedical subjects
Publications and source records attributed to B D Goldstein.
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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.
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.
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)
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)
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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.
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.
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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.
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.
The role of free radicals and active states of oxygen in human cancer is as yet unresolved. Various lines of evidence provide strong but inferential evidence that free radical reactions can be of crucial importance in certain carcinogenic mechanisms. A central point in considering free radical reactions in carcinogenesis is that human cancer is really a group of highly diverse diseases for which the initial causation and the progression to clinical disease occur through a wide variety of mechanisms. Furthermore, for many human cancers it appears that there are alternate pathways capable of tumor initiation and tumor progression. While for certain of these pathways free radical reactions appear necessary, it is unlikely that there are human cancers for which free radicals, or any other mechanism, are sufficient for the entire process beginning with the genetic alteration leading to a somatic mutation and eventually resulting in clinically overt disease. It is crucial that we view free radical reactions as among a panoply of mechanisms leading to human cancer, and consider research about the role of free radicals in cancer as opportunities to prevent the initiation or progression of human cancer.
Conditioning of the spinal monosynaptic reflex from cutaneous or muscle afferents results in facilitation followed by inhibition. We administered a series of agents which have been shown to alter the monosynaptic reflex by blocking specific inhibitory pathways. We found that administration of mecamylamine and atropine, agents which affect recurrent inhibition had no effect on the facilitation or inhibition of the MSR by conditioning the sural or medial gastrocnemius nerve. Similarly, bicuculline, an agent which blocks pre-synaptic inhibition, had no effect on the conditioning of the MSR. However, strychnine, a glycine antagonist which blocks post-synaptic inhibition, did alter both the facilitation and inhibition of the MSR by conditioning pulses. Strychnine enhanced the facilitation and partially blocked the inhibition of the MSR by both sural and medial gastrocnemius conditioning. These data show that the flexor reflex afferents and the larger diameter afferents alter the MSR solely through glycine-mediated post-synaptic inhibition.
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