Biomedical subjects
L Fishbein
Publications and source records attributed to L Fishbein.
New phenotypes associated with the swallow gene of Drosophila: evidence for a general role in oocyte cytoskeletal organization.
During oogenesis in Drosophila, several mRNAs and proteins are localized to discrete regions of the developing oocyte, resulting in a mature oocyte with a well-defined anterior-posterior axis. The product of the swallow (sww) gene is required for the localization of two different mRNAs during oogenesis, bicoid (bcd) and Adducin-like/hu-li tai shao (hts). We initiated a detailed characterization of the phenotypes associated with each of eight sww alleles as a means of investigating the role of sww in oogenic patterning. RNA localization defects in various sww mutants were examined by radioactive in situ hybridization to paraffin sections. Using this technique, several previously unreported RNA localization defects have been observed. Although bcd RNA localization is often lost completely in sww oocytes, in a high proportion of cases, bcd RNA is localized inappropriately along the periphery of the mature oocyte. In several sww mutants, a portion of the bcd mRNA population becomes concentrated at the posterior pole of the oocyte during late oogenesis. Several sww mutations also result in oskar RNA localization defects, consistent with a global role for sww in cytoskeletal regulation or organization. A detailed temporal and spatial analysis of hts RNA localization in sww mutants and in drug-treated ovaries reveals many similarities to bcd RNA localization, and implies the two independent localization events are accomplished by the same mechanism.
Pharmacokinetics and pharmacodynamic effects of nicotine nasal spray devices on cardiovascular and pulmonary function.
BACKGROUND: A nasal spray form of nicotine replacement therapy (Nicotrol NS, McNeil Consumer Products Co, Fort Washington, Pa) has been approved and, because of its rapid absorption across the nasal mucosa, may be more effective than nicotine gum or transdermal patches. We tested the hypothesis that the nicotine absorbed into the nasal mucosa would produce significant changes in hemodynamics and pulmonary function in 20 healthy, nonsmoking men and women. METHODS: In this double-blind, randomized study of Nicotrol NS versus placebo, we measured serum nicotine concentrations, blood pressure, heart rate, and indices of pulmonary function at timed intervals before and after nasal spray administration of 3 mg of nicotine. RESULTS: A peak serum nicotine concentration of 4.71 +/- 3.16 ng/mL occurred 10 minutes after drug administration. The maximum change in systolic blood pressure occurred 5 minutes after dosing and was significantly related to nicotine administration (7.1 +/- 9.4% for the nicotine group vs -1.6 +/- 7.3% for the placebo; P = 0.03). In contrast, neither diastolic blood pressure (P = 0.8) nor heart rate (P = 0.07) changed significantly after nicotine administration, when compared with placebo. Pulmonary function was not altered acutely by a single inhalation of nicotine. Pharmacokinetic modeling revealed a classic one-compartment model in which nicotine is absorbed into the systemic circulation by a zero-order process and eliminated by a first-order process. CONCLUSIONS: In this population of nonsmokers, hemodynamic effects of the nicotine nasal spray were observed shortly after administration and before the peak serum nicotine concentration.
Transmissible spongiform encephalopathies, hypotheses and food safety: an overview.
The transmissible spongiform encephalopathies (TSEs) (in both humans and animals) have been reviewed with the principal focus on bovine spongiform encephalopathy (BSE), its recent outbreak amongst cattle in the UK ('mad cow disease') and its sequelae. The possible reasons for this outbreak are discussed as well as a number of hypotheses reviewed for TSEs (e.g. prions, organophosphates, etc.) and current measures attendant with food safety and surveillance taken in the European Union. It is generally accepted that the combined weight of all the evidence to date supports the conclusion that the new rare but lethal variant Creutzfeldt-Jacob Disease (vCJD) is the human counterpart of the aetiological agent BSE and that eating meat from the infected animals is probably to blame for 24 deaths (23 in the UK and one in France) to date from vCJD. Considerable evidence from biochemical, immunologic, pathologic and genetic studies strongly suggests that PrpSC is the major component of the transmissible prion particle responsible for the rare fatal brain TSE diseases.
Handling and Disposal of Chemical Products/Management of Hospital Waste Substances and Residues.
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Effects of stones and other physical factors on the induction of rodent bladder cancer.
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Cooking, heating and air treatment pollutants in indoor environments.
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Exposure from occupational versus other sources.
There is an increasing need to consider the various routes of exposure to individuals in occupational settings, as well as the exposure of the general public to a broad spectrum of carcinogens. The need to consider indoor environments is increasingly recognized in light of the amount of time spent indoors by a large majority of the population and the recognition that levels of certain toxicants are higher indoors than outdoors. This overview highlights (i) a general comparison of exposure to indoor and outdoor levels of 12 volatile organic compounds and (ii) the exposure of workers and the general public to benzene, 1,3-butadiene, formaldehyde, styrene, tetrachloroethylene, phthalate esters, polychlorinated dibenzofurans, radon, and electromagnetic fields.
Technological changes in cancer prevention.
Exposures and technologies in the workplace are changing due to a variety of factors, including newly developed technologies, mechanization and automation, and improvements in industrial hygiene primarily effected in many developed countries. In addition substitution and removal of carcinogenic constituents in the workplace and general environment are increasing in a number of instances, particularly in North America, Western Europe, and Japan, and they are being accompanied as well by remediation either by source reduction, recycling, or compliance to more stringent national and international regulations and standards. This overview highlights some of the strategies employed in the technological changes in cancer prevention and cites examples in source reduction, changes in formulation, product or process changes, recycling, and hazardous materials management.
Chemicals used in the rubber industry.
Hundreds of chemicals and mixtures illustrative of many structural and use categories are employed in the rubber industry. Global utilization of natural rubber and synthetic elastomers as well as rubber-processing chemicals are projected to increase in the foreseeable future. Primary focus is centered on the major rubber processing chemicals and elastomer monomers in regard to their utility, production trends, structural characteristics, nature of potential impurities, and toxicology (primarily carcinogenicity and genotoxicity). Additionally, areas of specific exposure concern and epidemiology in the rubber industry are considered.
Approaches for assessing health risks from complex mixtures in indoor air: a panel overview.
Critical to a more definitive human health assessment of the potential health risks from exposure to complex mixtures in indoor air is the need for a more definitive clinical measure and etiology of the health effects of complex mixtures. This panel overview highlights six of the eight presentations of the conference panel discussion and features a number of the major topical areas of indoor air concern. W. G. Meggs assessed clinical research priorities with primary focus on the role of volatile organic chemicals in human health, recognizing the areas where definitive data are lacking. By recognizing many types of chemical sensitivity, it may be possible to design studies that can illuminate the mechanisms by which chemical exposure may cause disease. The critically important topic of multiple chemical sensitivity was discussed by N. A. Ashford, who identified four high risk groups and defined the demographics of these groups. P. A. Schulte addressed the issue of biological markers of susceptibility with specific considerations of both methodological and societal aspects that may be operative in the ability to detect innate or inborne differences between individuals and populations. Three case studies were reviewed. H. Anderson discussed the past and present priorities from a public health perspective, focusing on those issues dealing with exposures to environmental tobacco smoke and formaldehyde off-gassing from materials used in mobile home construction. J. J. Osborne described several case studies involving wood smoke exposure to children, with emphasis on the significantly greater occurrence of chronic respiratory symptoms and acute chest illness for children from homes heated with woodburning stoves.(ABSTRACT TRUNCATED AT 250 WORDS)
Xylenes: uses, occurrence and exposure.
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Past and present exposure determination techniques for benzene, toluene and xylene.
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Genetic effects of benzene, toluene and xylene.
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Benzene: uses, occurrence and exposure.
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Toluene: uses, occurrence and exposure.
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Fructooligosaccharides: a review.
Fructooligosaccharides are naturally occurring compounds that have been reported in a variety of plants. Neosugar is a fructooligosaccharide mixture of 1F-(1-beta-fructofuranosyl)-sucrose polymers which is produced on a commercial scale from sucrose using a fungal fructosyltransferase. The resulting product is 0.4 to 0.6 times as sweet as sugar and is resistant to digestion by mammalian alpha-amylase, sucrase and maltase. Although Neosugar is non-digestible in humans, it is selectively utilized by bifidobacteria. Neosugar has been examined extensively in human and animal studies which indicate a lack of toxicity, carcinogenicity and genotoxic effects. Neosugar is used as a feed additive for poultry and swine in Japan and has been approved in foods as a raw material. Additional studies in progress in the US suggest that it could provide an economic alternative as an additive to poultry and swine feed.
Perspectives of analysis of carcinogenic and mutagenic metals in biological samples.
There is a continuing need to assess the status of exposure to humans of the carcinogenic and/or mutagenic metals in both biological and environmental samples to better ensure that current or past exposures do not entail unacceptable health risks or to detect potentially excessive exposure before the appearance of adverse health effects. In order to more readily evaluate both the extent of exposure and trends of human exposure as well as the bioavailability, bioaccumulation and transport of these elements and their compounds, sensitive analytical procedures are required for their determination of the various oxidative states (as well as their organic derivatives) in complex matrices such as those found in both environmental and biological samples. The major objective of this overview is to highlight the more recent trends and state-of-the-art methodologies for the determination and speciation of arsenic, selenium, cadmium, chromium and nickel in human and animal tissues while concomitantly noting germane aspects of their bioavailability and interactions. Aspects of biological monitoring of the above elements will be stressed due to their potential utility in augmenting diverse epidemiologic and occupational health studies.