PubMed Health⌕ Search

Biomedical subjects

B W Wilson

Publications and source records attributed to B W Wilson.

At least 55 records · Page 3Linked to original sources
PubMed1992

Electric power, pineal function, and the risk of breast cancer.

Breast cancer is the leading cause of cancer death in women in the industrialized world, and the rates of breast cancer incidence are rising. Although risk is high in industrialized societies, it is low in nonindustrialized areas. The search for the causes of breast cancer has not yet yielded a convincing explanation for the geographic and temporal patterns in the occurrence of breast cancer. Generation of electric power is a hallmark of industrialization, and two products of electric power, light-at-night (LAN) and electromagnetic fields (EMF), may affect breast cancer risk. Exposure to either LAN or EMF can decrease production of melatonin by the pineal gland. Melatonin, in turn, has been shown to suppress mammary tumorigenesis in experimental animals. Moreover, recent epidemiological findings indicate an increased risk of breast cancer in workers occupationally exposed to EMF. On the basis of these considerations, it is proposed that the use of electrical power accounts, in part, for the higher risks of breast cancer in industrialized societies.

Animals↗
PubMed1992

Neurotoxicity of acute and repeated treatments of tabun, paraoxon, diisopropyl fluorophosphate and isofenphos to the hen.

The neuropathic potential of acute and repeated exposures of the phosphoramidates tabun (GA) and isofenphos (IFP), of diisopropyl fluorophosphate (DFP) and paraoxon (PO) were examined in the hen with treatments for up to 90 days via intramuscular injections of the highest tolerated doses with atropine protection. Plasma acetylcholinesterase (AChE), non-specific butyrylcholinesterase (BChE) and creatine kinase (CK) activities were measured in order to monitor whether the compounds were present at biologically active concentrations. Locomotor behavior was observed and tissues from the peripheral and central nervous systems were examined for signs of organophosphate-induced delayed neuropathy (OPIDN). No behavioral or histological evidence of OPIDN was observed after treatments with GA, IFP, PO, saline or atropine sulfate. DFP-treated birds displayed locomotor and neuropathological signs of OPIDN with a no effect level (NOEL) between 25 and 50 micrograms/kg.

Acetylcholinesterase↗
PubMed1992

Blood esterase determinations as markers of exposure.

The bases of using blood enzyme activity measurements [e.g. AChE, non-specific cholinesterase (BChE), carboxylesterase] as markers of organophosphate ester (OP) exposure are inhibition of activity by the binding of OPs to serine active sites in the enzymes, and the accessibility of the enzymes in RBCs and serum. The methods used to determine esterases in the blood of humans, experimental animals, and wildlife are outlined with emphasis on the acetylcholinesterase (AChE) of the red blood cell. Adaptations of an acetylthiocholine ester assay of Ellman et al. (1961) are common, but other colorimetric procedures, radiometric assays, and pH methods are also in use. Optimized, standardized methods are needed to assess exposures and provide a solid basis for risk assessment analyses. Useful adjuncts to ChE measurements are oxime reactivation tests and assay of neuropathy target esterase, an enzyme associated with organophosphate-induced delayed neuropathy. Determination of urinary metabolites compliments, but does not substitute for, the information obtained from blood ChE studies. Future assays are likely to involve antibodies to OP-protein complexes. Improvements in techniques permit the detection of small decreases in ChE activities. Whether or not such small decreases in ChE activities can, by themselves, constitute an adverse effect for input into risk assessment analyses is a controversial matter.

Biomarkers↗
PubMed1990

Characterization of neuropathy target esterase using trifluoromethyl ketones.

Neuropathy target esterase (NTE) is a membrane-bound carboxylesterase activity which is proposed as the target site in nerve tissue for initiation of organophosphate-induced delayed neuropathy. This activity is identified as phenyl valerate hydrolysis which is resistant to treatment with paraxon and sensitive to co-incubation with paraxon and mipafox. NTE preparations were obtained, which did not contain paraxon-sensitive or mipafox-resistant hydrolases, by selective reconstitution of detergent-solubilized NTE from chick embryo brain into asolectin vesicles during gel filtration. The topography of the catalytic site of NTE was then examined by investigating the inhibition of NTE by a series of 3-alkylthio- and 3-arylthio-1,1.1-trifluoro-propan-2-ones. These trifluoromethyl ketones were found to be rapidly reversible, competitive inhibitors of NTE with I50 values 1.3 x 10(-4) M to 4.9 x 10(-8) M. Correlation of I50 values with octanol/water partition coefficients (P), in the range of log P = 1.5 to 5.9. indicated that the optimal lipophilicity for NTE substrates and inhibitors is in the range of log P = 3.0 to 3.4. Electrophilic substitution at the meta position of aromatic rings increased the inhibitory capacity of these inhibitors, whereas substitution at the ortho position reduced inhibitory capacity. These results indicate both that a large hydrophobic pocket is closely associated with the catalytic residue of NTE, and that affinity for the active site is affected by steric and electronic parameters.

Animals↗
PubMed1990

Multiple molecular forms and lectin interactions of organophosphate-sensitive plasma and liver esterases during development of the chick.

Liver and plasma acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and carboxylesterase activities of the chick embryo and adult chickens were separated by sucrose density gradient sedimentation and further differentiated by their lectin affinities and organophosphate sensitivities. Changes in plasma cholinesterases during development indicated a characteristic shift in tetrameric (G4) isoforms from a slightly larger G4 AChE in the embryo to G4 BChE in the adult. These changes were not reflected in isoform patterns of liver homogenates, however. Interestingly, the time course of an increase in plasma BChE activity corresponded to the time course of a decrease in liver BChE activity, as if this enzyme was being mobilized and released. The distribution of liver esterases included both monomeric (G1) and G4 BChE and a large p-nitrophenylacetate (p-NPA) esterase activity that was separated into two main peaks by density gradient ultracentrifugation. The effects of organophosphate inhibitors indicated that the two liver p-NPA esterase activities may be regarded as carboxylesterases; however, these enzymes showed very different sensitivities to paraoxon and diisopropylfluorophosphate (DFP), with IC50 values differing by 3 and 4 orders of magnitude. Lectin affinity studies with multiple esterase forms suggested a heterogeneous group of glycoproteins that were packaged at different sites in the liver cell and were consistent with the presence of an intracellular precursor form to plasma BChE.

Animals↗
PubMed1990

Evidence for an effect of ELF electromagnetic fields on human pineal gland function.

A study was carried out to determine possible effects of 60-Hz electromagnetic-field exposure on pineal gland function in humans. Overnight excretion of urinary 6-hydroxymelatonin sulfate (6-OHMS), a stable urinary metabolite of the pineal hormone melatonin, was used to assess pineal gland function in 42 volunteers who used standard (conventional) or modified continuous polymer wire (CPW) electric blankets for approximately 8 weeks. Volunteers using conventional electric blankets showed no variations in 6-OHMS excretion as either a group or individuals during the study period. Serving as their own controls, 7 of 28 volunteers using the CPW blankets showed statistically significant changes in their mean nighttime 6-OHMS excretion. The CPW blankets switched on and off approximately twice as often when in service and produced magnetic fields that were 50% stronger than those from the conventional electric blankets. On the basis of these findings, we hypothesize that periodic exposure to pulsed DC or extremely low frequency electric or magnetic fields of sufficient intensity and duration can affect pineal gland function in certain individuals.

Adult↗
PubMed1990

The potential of transgenic animals for improved agricultural productivity.

The techniques involved in the transfer of foreign DNA to domestic animals have advanced to the stage where transgenic animals that express foreign genes can be reliably produced, albeit still at low efficiency. This paper reviews the current status of some of the more important areas in agriculture where this technology is being applied. Numerous attempts have been made to modify the growth performance characteristics of domestic animals by the introduction of metallothionein/growth hormone fusion genes. A summary of our work with transgenic sheep is presented. The results demonstrate that the unregulated production of growth hormone in transgenic sheep reduces carcass fat, elevates metabolic rate and heat production, causes skeletal abnormalities and impairs survival. The introduction of new metabolic pathways to domestic animals offers an attractive approach to improved animal productivity. This paper summarises recent results of research directed towards the introduction of a cysteine biosynthetic pathway and the glyoxylate cycle to transgenic sheep. So far, the genes encoding the enzymes have been isolated and expressed both in cells in culture and in transgenic mice. The results of work currently in progress demonstrate that some modification of the fusion genes is required to enhance their expression in transgenic animals.

Agriculture↗
PubMed1990

Developmental and maturational aspects of inherited avian myopathies.

Three inherited abnormalities of muscle growth of poultry are an inherited muscular dystrophy of the chicken, deep pectoral myopathy of turkeys and broilers, and focal myopathy of turkeys. The major features of each are described and compared. Cellular and molecular bases of dystrophy of the chicken and treatments to alleviate the disorder are discussed. The pathologic progression and anatomical basis for deep pectoral myopathy are presented. Evidence is given that focal myopathy of the turkey is a growth-dependent disorder. The implications of the idea that such disorders are partly consequences of selection are discussed in the context of the future needs of a poultry industry emphasizing processing of poultry meat.

Animals↗
PubMed1990

Turkey muscle growth and focal myopathy.

Muscle structure and blood enzyme activity were studied to 16 wk of age in lines of turkeys selected for rapid growth. The body and carcass weights were measured, frozen sections of breast and leg muscles examined, and plasma creatine kinase (CK) levels determined. Muscle weights were usually proportional to BW except for the relatively larger superficial pectoralis (SP) muscles in the most rapidly growing line. Damaged muscle fibers were found in all muscles examined, especially in the SP of the breast, the gastrocnemius (GA), and other muscles of the leg; these damages became more common from 10 to 16 wk of age. There were more degenerating muscle fibers and higher levels of plasma CK in the rapidly growing lines than in a slower growing unselected line. The findings support the idea that a focal myopathy, unrelated to deep pectoral myopathy or to inherited muscular dystrophy of the chicken, is associated with rapid growth of turkeys.

Animals↗
PubMed1990

Acetylcholinesterase and neuropathy target esterase in chickens treated with acephate.

Reports that near-lethal doses of the pesticide methamidophos (O,S-dimethyl phosphoramidothioate) caused a delayed neurotoxicity (OPIDN) in humans and that another phosphoramidate, isofenphos, caused OPIDN in the hen at high doses, prompted a study of the abilities of acephate (O,S-dimethyl acetylphosphoramidothioate) to inhibit brain acetylcholinesterase (AChE) and neuropathy target esterase (NTE) in vivo. Hens were treated orally with 5-700 mg/kg of acephate, or im with 50-200 micrograms/kg of diisopropyl-fluorophosphate (DFP, positive control) and sacrificed 24 hr later. Brain homogenates were assayed for AChE as an estimate of acute toxicity, for NTE to indicate acephate's potential to cause OPIDN, and for residues of acephate and its metabolite methamidophos. A range finding study confirmed the LD50 level for acephate was approximately 800 mg/kg. Regression analyses indicated an ID50 (a dose that inhibits 50% of activity) for acephate inhibition of AChE of 10 mg/kg and an extrapolated ID50 for inhibition of NTE of 1300 mg/kg, almost twice the LD50. In contrast, ID50 values for DFP were similar for AChE (146 micrograms/kg) and NTE (132 micrograms/kg). Brain methamidophos levels were 10 to 16 percent of the total acephate plus methamidophos brain concentration. The lower the dose of acephate, the higher was the relative percentage of methamidophos. The results show acephate is a more potent inhibitor of AChE than it is of NTE in hens and suggest it would be difficult to administer a single dose of acephate sufficient to cause OPIDN without killing the animal.

Animals↗
PubMed1989

Correlation of neuropathy target esterase activity with specific tritiated di-isopropyl phosphorofluoridate-labelled proteins.

Neuropathy target esterase (NTE) is a membrane-bound carboxylesterase activity that has been proposed as the target site for initiation of organophosphate-induced delayed neuropathy. This activity is identified by its resistance to treatment with Paraoxon and sensitivity to co-incubation with Paraoxon and Mipafox. Sucrose-density-gradient centrifugation of membrane-associated proteins isolated from chick-embryo brains identified three proteins, Mr 161,000, 116,500 and 103,000, that were labelled with [3H]di-isopropyl phosphorofluoridate in an NTE-like manner and that co-migrated with NTE. The 161,000-Mr and 116,500-Mr proteins were identified in both adult and embryo brain. One or both of these proteins may therefore contribute to the activity defined as NTE. In addition, a 61,000-Mr protein was identified that does not comigrate with NTE, but that was labelled with [3H]di-isopropyl phosphorofluoridate in a Paraoxon-resistant and Mipafox-sensitive manner. The effect of Mipafox on labelling, however, was reversibly blocked by co-incubation with Paraoxon. This protein, therefore, is not NTE, but has the necessary inhibitor-sensitivity to be the target site for organophosphate-induced delayed neuropathy.

Animals↗
PubMed1989

Neuroendocrine mediated effects of electromagnetic-field exposure: possible role of the pineal gland.

Reports from recent epidemiological studies have suggested a possible association between extremely low frequency (ELF; including 50- or 60-Hz) electric- and magnetic-field exposure, and increased risk of certain cancers, depression, and miscarriage. ELF field-induced pineal gland dysfunction is a possible etiological factor in these effects. Work in our laboratory and elsewhere has shown that ELF electromagnetic-field exposure can alter the normal circadian rhythm of melatonin synthesis and release in the pineal gland. Consequences of reduced or inappropriately timed melatonin release on the endocrine, neuronal, and immune systems are discussed. Laboratory data linking ELF field exposure to changes in pineal circadian rhythms in both animals and humans are reviewed. The authors suggest that the pineal gland, in addition to being a convenient locus for measuring dyschronogenic effects of ELF field exposure, may play a central role in biological response to these fields via alterations in the melatonin signal.

Animals↗
PubMed1988

Complete sequence of a type-I microfibrillar wool keratin gene.

We have isolated and sequenced the gene encoding a type-I microfibrillar wool keratin (47.6 kDa) together with about 500 bp of flanking DNA at each end. The primary transcript is 5180 bp in length, with seven exons. The positions of the introns are highly conserved in regions of the gene coding for the alpha-helical protein domains common to all intermediate filaments. The 5'-flanking region contains sequences similar to published consensus sequences from a variety of other keratins, including the high-sulfur wool matrix proteins. Further upstream, this region also contains artiodactyl-specific middle-repetitive DNA of the 'C-A3' family and intron II displays regions similar to a recently described sequence known as an Art2 element.

Amino Acid Sequence↗
PubMed1988

Chronic exposure to ELF fields may induce depression.

Exposure to extremely-low-frequency (ELF) electric or magnetic fields has been postulated as a potentially contributing factor in depression. Epidemiologic studies have yielded positive correlations between magnetic- and/or electric-field strengths in local environments and the incidence of depression-related suicide. Chronic exposure to ELF electric or magnetic fields can disrupt normal circadian rhythms in rat pineal serotonin-N-acetyltransferase activity as well as in serotonin and melatonin concentrations. Such disruptions in the circadian rhythmicity of pineal melatonin secretion have been associated with certain depressive disorders in human beings. In the rat, ELF fields may interfere with tonic aspects of neuronal input to the pineal gland, giving rise to what may be termed "functional pinealectomy." If long-term exposure to ELF fields causes pineal dysfunction in human beings as it does in the rat, such dysfunction may contribute to the onset of depression or may exacerbate existing depressive disorders.

Animals↗
PubMed1988

Reduction of the nocturnal rise in pineal melatonin levels in rats exposed to 60-Hz electric fields in utero and for 23 days after birth.

Rats exposed to 60-Hz electric fields of either 10, 65, or 130 kV/m from conception to 23 days of age exhibited reduced peak nighttime pineal melatonin contents compared to unexposed controls. As a group, the exposed rats also exhibited a phase delay, estimated at approximately 1.4 hours, in the occurrence of the nocturnal melatonin peak. No clear dose-response relationship was noticed over the range of electric field strengths used as treatments in these experiments. These are the first studies concerned with the effects of electric field exposure on the pineal melatonin rhythm in immature rats. The findings are generally consistent with those obtained using adult rats, where electric field exposure has been shown to abolish the nighttime rhythm in pineal melatonin concentrations.

Animals↗