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E Bingham

Publications and source records attributed to E Bingham.

At least 19 recordsLinked to original sources
PubMed2002

The role of hepatic portal glucose sensing in modulating responses to hypoglycaemia in man.

AIMS/HYPOTHESIS: The role of glucose sensing cells in the human hepatic portal system in the initiation of the neuroendocrine responses to acute hypoglycaemia is not known. We investigated the effect of raising blood glucose concentrations in the hepatic-portal vein on neurohumoral responses during induction of systemic hypoglycaemia in nine healthy male volunteers. METHODS: Each subject received an insulin infusion (3 mU.kg(-1).min(-1)) on two occasions, in random order. Variable rate glucose infusion was used to maintain plasma glucose at 5 mmol/l for 60 min, then 3.2 mmol/l for 60 min. At 20 min prior to hypoglycaemia, subjects drank 20 g of glucose in water or water sweetened with saccharin. In five of the volunteers, the oral glucose was labelled with U-13C6 glucose, which showed peak systemic glucose absorption between 90 and 110 min. Five volunteers also repeated the study with a euglycaemic clamp. RESULTS: Oral glucose was associated with a reduction in the early adrenaline response to hypoglycaemia, the area under the curve from 90 to 110 min falling from 24.02+/-20.84 (means +/- SD) to 15.26+/-13.65 nmol/l per 20 min, p<0.05. Symptom scores (area under curve) decreased from 99.72+/-91.86 to 16.39+/-94.71, p=0.008 (total), 51.8+/-68.61 to 7.78+/-41.61, p=0.03 (autonomic) and 54.17+/-50.61 to 8.6+/-57.99 with oral glucose, p=0.001 (neuroglycopenic). Oral glucose did not influence symptoms during euglycaemia. CONCLUSION/INTERPRETATION: Our data are compatible with the hypothesis that centrally mediated symptomatic and neuroendocrine responses are attenuated by glucose detection in the hepatic portal vein in humans.

Adaptation, Physiological↗
PubMed2001

Pharmacogenomics: out of the lab and into the community.

Pharmacogenomics is the study of the inherited basis of differences in response to drugs. These interindividual differences are often more than tenfold; a 'slow metabolizer' or 'low-responsive' individual might therefore require ten times less than the recommended dose of a drug than a 'rapid metabolizer' or 'high-responsive' person, and the slow metabolizer is often more likely to experience drug toxicity than a rapid metabolizer. Our knowledge is developing rapidly to the point that the physician will soon use DNA-based tests to aid in decision-making with respect to the most appropriate drug and dosage given to each patient. If the patient's DNA is available, however, what boundaries should be placed on that DNA? If the patient's genotype becomes known to the physician (and presumably to the patient him- or herself), what ethical questions might arise and how will they be resolved? This article discusses these issues and outlines some of the possible solutions.

Base Sequence↗
PubMed2001

Pathogenomic mechanisms for particulate matter induction of acute lung injury and inflammation in mice.

To begin identifying genes controlling individual susceptibility to particulate matter, responses of inbred mouse strains exposed to nickel sulfate (NiSO4*) were compared with those of mice exposed to ozone (O3) or polytetrafluoroethylene (PTFE). The A strain was sensitive to NiSO4-induced lung injury (quantified by survival time), the C3H/He (C3) strain and several other strains were intermediate in their responses, and the C57BL/6 (B6) strain was resistant. The strains showed a pattern of response similar to the patterns of response to O3 and PTFE. The phenotype of A x B6 offspring (B6AF1) resembled that of the resistant B6 parental strain, with strains exhibiting sensitivity in the order A > C3 > B6 = B6AF1. Pathology was comparable for the A and B6 mice, and exposure to NiSO4 at 15 microg/m3 produced 20% mortality in A mice. Strain sensitivity for the presence of protein or neutrophils in lavage fluid differed from strain sensitivity for survival time, suggesting that they are not causally linked but are controlled by an independent gene or genes. In the B6 strain, exposure to nickel oxide (NiO) by instillation (40 to 1000 nm) or inhalation (50 nm) produced no changes, whereas inhalation of NiSO4 (60 or 250 nm) increased lavage proteins and neutrophils. Complementary DNA (cDNA) microarray analysis with 8,734 sequence-verified clones revealed a temporal pattern of increased oxidative stress, extracellular matrix repair, cell proliferation, and hypoxia, followed by a decrease in surfactant-associated proteins (SPs). Certain expressed sequence tags (ESTs), clustered with known genes, suggest possible coregulation and novel roles in pulmonary injury. Finally, locus number estimation (Wright equation) and a genomewide analysis suggested 5 genes could explain the survival time and identified significant linkage for a quantitative trait locus (QTL) on chromosome 6, Aliq4 (acute lung injury QTL4). Haplotype analysis identified an allelic combination of 5 QTLs that could explain the difference in sensitivity to acute lung injury between parental strains. Positional candidate genes for Aliq4 include aquaporin-1 (Aqp1), SP-B, and transforming growth factor-alpha (TGF-alpha). Transgenic mice expressing TGF-alpha were rescued from NiSO4 injury (that is, they had diminished SP-B loss and increased survival time). These findings suggest that NiSO4-induced acute lung injury is a complex trait controlled by at least 5 genes (all possibly involved in cell proliferation and surfactant function). Future assessment of these susceptibility genes (including evaluations of human synteny and function) could provide valuable insights into individual susceptibility to the adverse effects of particulate matter.

Air Pollutants↗
PubMed2000

Autosomal dominant hemorrhagic macular dystrophy not associated with the TIMP3 gene.

OBJECTIVE: To describe the ophthalmic and genetic findings of a large kindred (UM:H389) with autosomal dominant hemorrhagic macular dystrophy. METHODS: The disease state of family members was documented by dilated fundus examination, electroretinography, color vision tests, fluorescein angiography, measurement of visual fields, biomicroscopy, gonioscopy, and intraocular pressure measurement. Linkage and haplo-type analyses were carried out with markers flanking the Sorsby fundus dystrophy TIMP3 (tissue inhibitor of metalloproteinase 3) gene locus, and mutation analysis was carried out by screening exon 5 of the TIMP3 gene. RESULTS: This 4-generation pedigree with autosomal dominant hemorrhagic macular degeneration has visual symptoms beginning in the sixth decade of life. Several family members developed choroidal neovascular membrane formation in the macula of both eyes. The phenotype overlaps that of Sorsby fundus dystrophy. Some of the affected members have unusual zonularlike radial striations on the anterior lens capsule surface, and glaucoma or ocular hypertension has developed in 2 of them. Involvement of the TIMP3 gene was excluded by linkage, haplotype, and mutation analyses. CONCLUSIONS: The phenotype of this family with autosomal dominant macular dystrophy overlaps that of Sorsby fundus dystrophy. Exclusion of the TIMP3 gene in this family indicates genetic heterogeneity for hemorrhagic macular dystrophy. Anterior segment anomalies may occur with this condition, but cosegregation has not yet been established. CLINICAL RELEVANCE: This study broadens the spectrum of hemorrhagic macular dystrophy by identifying a family in which the TIMP3 gene is not involved. Once the gene is cloned, we are eager to learn whether this gene may be involved in age-related macular degeneration.

Adult↗
PubMed2000

A curriculum for environmental genetics education.

INTRODUCTION: Environmental genetics is a scientific area concerned with interactions between genes and the environment. Progress in this field, coupled with the growth in genetic testing, has great potential for improving human health. There are also ethical, legal, and social concerns surrounding advances in environmental genetics and genetic testing. Because genetic information is rapidly increasing in our society, the public needs to learn more about scientific progress and policy issues in these areas. OBJECTIVE: To describe a curriculum for the public on environmental genetics and genetic testing. PROGRAM: In 1998, the Department of Environmental Health (Center for Environmental Genetics), University of Cincinnati, began an outreach project for the public called Learning Exchange for Genetic and Environmental Disease Solutions (LEGENDS). The project fosters awareness and understanding of environmental genetics and genetic testing with discussion of related policy issues. The curriculum includes brief lectures and discussions based on thematic modules and a set of interactive exercises to be conducted in small groups. More than 100 persons have attended instructional sessions sponsored by LEGENDS at the time of this writing. SIGNIFICANCE: The curriculum appears to be a potentially useful resource for educating the public about environmental genetics, genetic testing, and related policy issues. This project has implications for other organizations working to further genetics education.

Confidentiality↗
PubMed2000

Vagal nerve stimulation in patients with refractory epilepsy. Effect on seizure frequency, severity and quality of life.

Vagal nerve stimulation using an NCP (Cyberonics) device has been suggested as a potential treatment for patients with epilepsy that has previously proven refractory. Ten patients in Northern Ireland have had this device implanted and been fully audited pre- and post-operatively. Twelve months post-implantation, five patients have demonstrated a greater than 50% reduction in seizure frequency. A statistical reduction in seizure severity of the ictal phase of the major seizures has also been shown. Improvement in the patients' overall quality of life has, however, not been demonstrated in parallel to seizure reduction.

Adolescent↗
PubMed2000

A fast fixed-point algorithm for independent component analysis of complex valued signals.

Separation of complex valued signals is a frequently arising problem in signal processing. For example, separation of convolutively mixed source signals involves computations on complex valued signals. In this article, it is assumed that the original, complex valued source signals are mutually statistically independent, and the problem is solved by the independent component analysis (ICA) model. ICA is a statistical method for transforming an observed multidimensional random vector into components that are mutually as independent as possible. In this article, a fast fixed-point type algorithm that is capable of separating complex valued, linearly mixed source signals is presented and its computational efficiency is shown by simulations. Also, the local consistency of the estimator given by the algorithm is proved.

Algorithms↗
PubMed2000

Genetic susceptibility to irritant-induced acute lung injury in mice.

Recent studies suggest that genetic variability can influence irritant-induced lung injury and inflammation. To begin identifying genes controlling susceptibility to inhaled irritants, seven inbred mouse strains were continuously exposed to nickel sulfate (NiSO(4)), polytetrafluoroethylene, or ozone (O(3)), and survival time was recorded. The A/J (A) mouse strain was sensitive, the C3H/He (C3) strain was intermediate, and the C57BL/6 (B6) strain was resistant to NiSO(4)-induced acute lung injury. The B6AF(1) offspring were also resistant. The strain sensitivity pattern for NiSO(4) exposure was similar to that of polytetrafluoroethylene or ozone (O(3)). Pulmonary pathology was comparable for A and B6 mice. In the A strain, 15 microg/m(3) of NiSO(4) produced 20% mortality. The strain sensitivity patterns for lavage fluid proteins (B6 > C3 > A) and neutrophils (A >/= B6 > C3) differed from those for acute lung injury. This phenotype discordance suggests that these traits are not causally linked (i.e., controlled by independent arrays of genes). As in acute lung injury, B6C3F(1) offspring exhibited phenotypes (lavage fluid proteins and neutrophils) resembling those of the resistant parental strain. Agreement of acute lung injury strain sensitivity patterns among irritants suggested a common mechanism, possibly oxidative stress, and offspring resistance suggested that sensitivity is inherited as a recessive trait.

Acute Disease↗
PubMed1996

Urine toxicology screens in drivers suspected of driving while impaired from drugs.

OBJECTIVE: Police departments, in conjunction with the National Highway Traffic Safety Administration, have developed a standardized evaluation aimed at identifying drivers impaired by drugs other than ethanol. These evaluations are performed by specially trained police officers known as Drug Recognition Experts. METHODS: We retrospectively reviewed the evaluations of 242 drivers detained for driving while impaired in the City and County of Denver from January 1, 1988 to June 30, 1990. RESULTS: All drivers had urine toxicology screens performed, which were positive for a mean 1.2 +/- 0.9 SD (range zero to four) for drugs having the potential for causing driving impairment. The 193/242 urine screens (79.8%) testing positive showed the following drugs: cannabis 162 (66.9%), stimulants (including cocaine metabolites) 80 (33.1%), depressants (benzodiazepines and barbiturates) 24 (9.9%), narcotics 12 (5.0%), inhalants (toluene) 1 (0.4%), hallucinogens (LSD) 1 (0.4%), and other 3 (1.2%). Drug Recognition Experts, based on their initial evaluation, were able to predict correctly some or all of the drugs found on the urine screens in 178/242 (73.6%) of cases. Overall agreement between the Drug Recognition Experts opinions and urine screen results had a kappa value (p < 0.05) of 0.41. CONCLUSIONS: There was a high rate (79.8%) of positive urine toxicology screens in drivers suspected of nonethanol drug impairment. In most cases, Drug Recognition Experts were able to reliably predict the results of these screens.

Adolescent↗
PubMed1996

A recombination outside the BB deletion refines the location of the X linked retinitis pigmentosa locus RP3.

Genetic loci for X-linked retinitis pigmentosa (XLRP) have been mapped between Xp11.22 and Xp22.13 (RP2, RP3, RP6, and RP15). The RP3 gene, which is responsible for the predominant form of XLRP in most Caucasian populations, has been localized to Xp21.1 by linkage analysis and the map positions of chromosomal deletions associated with the disease. Previous linkage studies have suggested that RP3 is flanked by the markers DXS1110 (distal) and OTC (proximal). Patient BB was thought to have RP because of a lesion at the RP3 locus, in addition to chronic granulomatous disease, Duchenne muscular dystrophy (DMD), mild mental retardation, and the McLeod phenotype. This patient carried a deletion extending approximately 3 Mb from DMD in Xp21.3 to Xp21.1, with the proximal breakpoint located approximately 40 kb centromeric to DXS1110. The RP3 gene, therefore, is believed to reside between DXS1110 and the proximal breakpoint of the BB deletion. In order to refine the location of RP3 and to ascertain patients with RP3, we have been analyzing several XLRP families for linkage to Xp markers. Linkage analysis in an American family of 27 individuals demonstrates segregation of XLRP with markers in Xp21.1, consistent with the RP3 subtype. One affected mate shows a recombination event proximal to DXS1110. Additional markers within the DXS1110-OTC interval show that the crossover is between two novel polymorphic markers, DXS8349 and M6, both of which are present in BB DNA and lie centromeric to the proximal breakpoint. This recombination places the XLRP mutation in this family outside the BB deletion and redefines the location of RP3.

Adult↗
PubMed1996

Sorsby's fundus dystrophy in a family with a Ser-181-CVS mutation in the TIMP-3 gene: poor outcome after laser photocoagulation.

PURPOSE: Mutations in the TIMP-3 (tissue inhibitor of metalloproteinase-3) gene can cause Sorsby's fundus dystrophy (SFD) and lead to choroidal neovascular membrane (CNV) formation. We studied a large American family of Irish Protestant descent with CNV inherited as an autosomal dominant trait, to determine the phenoptype and to learn whether a mutation was present in TIMP-3. METHODS: Twelve members of 5 generations were evaluated clinically, with psychophysical and electroretinographic testing, and by fluorescein angiography. Blood samples for DNA extraction were obtained from 21 affected and unaffected family members and from 1 unrelated spouse. DNA sequence was determined, and affected individuals showed a Ser-181-Cys mutation in TIMP-3 exon 5. RESULTS: Observable pathology involved primarily the macula, and both the full-field ERG and visual fields were normal. Acute CNV occurred during the third through fifth decades, with second eyes typically also affected during the subsequent year. Three affected members complained of nyctalopia prior to developing CNV. A Ser-181-Cys mutation in the TIMP-3 gene cosegregated with CNV in 10 affected subjects but was absent in 3 relatives at risk and sufficiently old to trust the clinical designation of normalcy. Nine eyes of 6 family members were treated by laser photocoagulation by 5 different ophthalmologists for foveal and juxtafoveal CNV. All eyes had recurrent CNV and lost acuity to 20/300 or less within several months. CONCLUSIONS: Laser photocoagulation of CNV did not stem vision loss in this SFD family. Although possible benefits of laser treatment were not put to formal clinical trial owing to the limited number of Sorsby's cases, it appears that photocoagulation is not of long-term benefit for preserving vision loss from the TIMP-3 Ser-181-Cys mutation. Several younger family members with the mutation are thus far not clinically affected and are being followed up.

Adult↗
PubMed1995

Chemical mixtures from a public health perspective: the importance of research for informed decision making.

When considered from a public health perspective, the central question regarding chemical mixtures is deceptively simple: Are current approaches to risk assessment for chemical mixtures affording effective (adequate) and efficient (cost-effective) protection for members of our society? Answering this question realistically depends on an understanding of the hierarchical goals of public health (i.e. prevention, intervention, treatment) and an accurate evaluation of the extent to which these goals are being achieved. To allow decision makers to make informed judgments about the health risks of chemical mixtures, adequate scientific knowledge and understanding must be available to support risk assessment activities, which are an integral part of the regulatory decision making process. Designing and implementing relevant research depends on the existence of a feedback loop between researchers and regulators, where the information needs of regulators influence the nature and direction of research and the information and understanding generated by researchers improves the scientific basis for public health decisions. A clear, consistent, commonly accepted taxonomy for describing important mixture-related phenomena is a key factor in creating and maintaining the necessary feedback loop. Ultimately, both researchers and regulators share a common goal with regard to chemical mixtures; improving the state-of-the-science so that we can make informed decisions about protecting public health. A survey of research issues and needs that are crucial to attaining this goal is presented.

Decision Making↗
PubMed1993

Factors affecting carcinogenic potential of mixtures.

Historically, exposure to complex mixtures such as soot, coal tar, mineral oils, and cigarette smoke has been associated with increased cancer mortality. Benzo[a]pyrene (BaP) has been used to predict the carcinogenic potency of mixtures. Two complete carcinogenicity C3H/HEJ mouse skin bioassays were undertaken to determine the effect of low doses of BaP on the carcinogenic potential of mixtures. A toluene solution containing 0.1% each of five noncarcinogenic polycyclic aromatic hydrocarbons (PAHs), anthracene, chrysene, pyrene, fluoroanthene, and phenanthrene, produced tumors in 23% of the mice with a latent period of 73 weeks. With the addition of a 0.001% BaP to the above solution, 47% of the mice produced tumors with a latent period of 66 weeks. In the second study, coal tar in toluene, which was determined to contain 0.0006% BaP, produced tumors in 51% of mice with a latent period of 73 weeks. In both studies the BaP solutions by themselves did not produce tumors. In a third study, the 9-, 2-, and 3-methylbenz[a]-anthracene compounds were noncarcinogenic using toluene as the solvent. With the substitution of n-dodecane for toluene all three compounds produced significant numbers of tumors. The results indicate that (1) low dose levels of BaP can have an impact on the carcinogenic potential of mixtures, (2) the presence or absence of BaP is not always sufficient to account for the observed potency and the synergistic effects of other substances which might be present, and (3) that certain noncarcinogenic methylbenz[a]anthracenes can have their carcinogenic potential altered by a change in the solvent used.

Alkanes↗
PubMed1990

Standards, regulation, and public health.

The period from 1900 to about 1914 produced more than 100 initiatives by the federal government to regulate the food and drug supply. In the period from about 1914 until the latter part of the 1930s, attention focused on occupational exposures. The passage of the Walsh-Healey Act in 1936 led to the need to develop exposure limits (standards) for contaminants in industrial operations. During the 1960s, the environmental movement emerged, resulting in various laws to protect the public health beginning around 1970. The interplay of factors necessary to prevent environmentally induced diseases is complex, but standards are considered to be objective indicators of successful preventive measures or strategies. The roles or activities of various entities in establishing these standards are critical and include research, education, health professionals, professional organizations, and the government.

Environmental Health↗
PubMed1990

Occupational bladder cancer in textile dyeing and printing workers: six cases and their significance for screening programs.

Occupational bladder cancer due to aniline dye intermediates such as beta-naphthylamine and benzidine has long been known; benzidine congeners (o-tolidine and o-dianisidine) are highly suspect. Among 400 men from the Amalgamated Clothing and Textile Workers Union (ACTWU) Dyers locals in New York and New Jersey screened over a 4-year period, two cases of bladder cancer were detected. (Microscopic hematuria, not cytological evaluation, prompted further investigation.) Before a 1984 ACTWU screening program in North Carolina, three workers from the same plant self-reported bladder cancers. Another member, with inconclusive screening results, was diagnosed 2 years later. For these six cases, the mean age at detection was 56.5 years (age range, 38 to 79 years), a decade earlier than age at diagnosis of nonoccupational bladder cancer in men. The average latency from onset of exposure to diagnosis was 23.3 years. These cancers provide evidence to support the initiation of screening programs for high-risk workers. To overcome the emotional and economic disincentives faced by potential victims of occupational bladder cancer, training programs are needed. Worker involvement is required, through trade union representation where possible, to assure reliable training and the equitable distribution of screening and treatment costs.

Adult↗