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Biomedical subjects

D E Barnes

Publications and source records attributed to D E Barnes.

At least 37 records · Page 2Linked to original sources
PubMed1995

Looking through a keyhole at the tobacco industry. The Brown and Williamson documents.

OBJECTIVE: To introduce a series of papers discussing previously undocumented tobacco industry activities regarding strategies to avoid products liability litigation, understand nicotine addiction, and manipulate both internal and external scientific research on the effects of both active and passive smoking. DATA SOURCES: Documents from Brown and Williamson Tobacco Corporation (B&W), the British American Tobacco Company (BAT), and other tobacco interests provided by an anonymous source, obtained from Congress, and received from the private papers of a former BAT officer. STUDY SELECTION: All available materials, including confidential reports regarding research and internal memoranda exchanged between tobacco industry lawyers. CONCLUSIONS: These documents provide our first look at the inner workings of the tobacco industry during the crucial period in which the scientific case that smoking is addictive and kills smokers solidified. The documents show a sophisticated legal and public relations strategy to avoid liability for the diseases induced by tobacco use. The documents show that lawyers steered scientists away from particular research avenues, which is inconsistent with the company's purported disbelief in the causation and addiction claims; if the company had been genuinely unconvinced by the causation and addiction hypotheses, then it should have had no concern that new research would provide ammunition for the enemy. Quite the contrary, the documents show that B&W and BAT recognized more than 30 years ago that nicotine is addictive and that tobacco smoke is "biologically active" (eg, carcinogenic).

Humans↗
PubMed1995

Nicotine and addiction. The Brown and Williamson documents.

OBJECTIVE: To learn how nicotine has been regarded by a major tobacco company. DATA SOURCES: Documents from Brown and Williamson Tobacco Corporation (B&W), the British American Tobacco Company (BAT), and other tobacco interests provided by an anonymous source, obtained from Congress, and received from the private papers of a former BAT officer. STUDY SELECTION: All available materials, including confidential reports regarding research and internal memoranda exchanged between tobacco industry lawyers. CONCLUSIONS: During a period of 22 years (1962 to 1984), employees of B&W and BAT conducted research and commented on the pharmacology of nicotine. They consistently regarded nicotine as the pharmacological agent that explained tobacco use. In the early part of the period under study, officials of the companies wrote about nicotine addiction explicitly. Inhalation of cigarette smoke by the consumer was recognized throughout the period as necessary for the normal function of a cigarette. The documents contain little indication that research was conducted on either the taste or the flavor of nicotine. The documents reveal an intention on the part of B&W and its corporate parent to affect the function of the body with nicotine.

Commerce↗
PubMed1995

Lawyer control of internal scientific research to protect against products liability lawsuits. The Brown and Williamson documents.

OBJECTIVE: To understand how attorneys for the tobacco industry in general, and Brown and Williamson Tobacco Corporation (B&W) in particular, have responded to the threat of products liability litigation arising from smoking-induced diseases. DATA SOURCES: Documents from B&W, the British American Tobacco Company (BAT), and other tobacco interests provided by an anonymous source, obtained from Congress, or received from the private papers of a former BAT officer. STUDY SELECTION: All available materials, including confidential reports regarding research and internal memoranda exchanged between tobacco industry lawyers. CONCLUSIONS: The documents demonstrate that the tobacco industry in general, and B&W in particular, were very concerned about the threat of products liability lawsuits, and they illustrate some of the steps taken by lawyers at one company to avoid the discovery of documents that might be useful to a plaintiff in such a lawsuit. These steps included efforts to control the language of scientific discourse on issues related to smoking and health, to bring all potentially damaging internal scientific documents under attorney work product and attorney-client privilege to avoid discovery, to remove "deadwood" documents, and to insulate B&W from knowledge of potentially damaging scientific information from other BAT companies.

Consumer Product Safety↗
PubMed1995

Lawyer control of the tobacco industry's external research program. The Brown and Williamson documents.

OBJECTIVE: To examine the involvement of tobacco industry lawyers in the selection of tobacco industry scientific research projects and to examine how the research was used to influence public policy. DATA SOURCES: Documents from Brown and Williamson Tobacco Corporation, the British American Tobacco Company (BAT), and other tobacco interests provided by an anonymous source, obtained from Congress, and received from the private papers of a former BAT officer. STUDY SELECTION: All available materials, including confidential reports regarding research and internal memoranda exchanged between tobacco industry lawyers. CONCLUSIONS: The involvement of tobacco industry lawyers in the selection of scientific projects to be funded is in sharp contrast to the industry's public statements about its review process for its external research program. Scientific merit played little role in the selection of external research projects. The results of the projects were used to generate good publicity for the industry, to deflect attention away from tobacco use as a health danger, and to attempt, sometimes surreptitiously, to influence policymakers.

Humans↗
PubMed1995

Acoustic stimulation of the semicircular canals.

Stimulation of the semicircular canals provides an alternative method of vibratory stimulation of the auditory system. The frequency response characteristics of stimulation of the tympanic membrane, malleus, stapes, round window, and fenestrated semicircular canal are presented in this article.

Animals↗
PubMed1994

Aberrant DNA repair and DNA replication due to an inherited enzymatic defect in human DNA ligase I.

Two missense mutations in different alleles of the DNA ligase I gene have been described in a patient (46BR) with immunodeficiencies and cellular hypersensitivity to DNA-damaging agents. One of the mutant alleles produces an inactive protein, while the other encodes an enzyme with some residual activity. A subline of identical phenotype that is homozygous (or hemizygous) for the mutant allele encoding this partially active enzyme has facilitated characterization of the enzymatic defect in 46BR. This subline retains only 3 to 5% of normal DNA ligase I activity. The intermediates in the ligation reaction, DNA ligase I-AMP and nicked DNA-AMP, accumulate in vitro and in vivo. The defect of the 46BR enzyme lies primarily in conversion of nicked DNA-AMP into the final ligated DNA product. Assays of DNA repair in 46BR cell extracts and of DNA replication in permeabilized cells have clarified functional roles of DNA ligase I. The initial rate of ligation of Okazaki fragments during DNA replication is apparently normal in 46BR cells, but 25 to 30% of the fragments remain in low-molecular-weight form for prolonged times. DNA base excision repair by 46BR cell extracts shows a delay in ligation and an anomalously long repair patch size that is reduced upon addition of purified normal DNA ligase I.

Adenosine Monophosphate↗
PubMed1994

Particle repositioning maneuver for benign paroxysmal positional vertigo.

The recent demonstration of free-floating particles in the endolymph of the posterior semicircular canal in patients with benign paroxysmal positional vertigo (BPPV) has renewed interest in the physiology and treatment of this entity. The particle repositioning maneuver (PRM) relocates the free-floating particles from the posterior semicircular canal back into the utricle, relieving the patient of bothersome, often long-standing vertigo. This report represents a prospective study of 27 consecutive patients seen with a diagnosis of BPPV. Eighty-four percent of the patients treated with the particle repositioning maneuver who had no other associated pathology were cured or significantly improved with this new technique. Two patients who failed conservative management went on to surgical intervention with the posterior semicircular canal occlusion. The authors find the particle repositioning maneuver effective for many patients with benign positional vertigo and recommend it as the first-line treatment modality for BPPV.

Adult↗
PubMed1993

DNA repair.

Multiple DNA repair processes are required to maintain the integrity of the cellular genome. Recent advances, including elucidation of three-dimensional structures of DNA repair enzymes, and the cloning and characterization of DNA repair genes implicated in human inherited disease, have given new insights into the surprising complexity of cellular responses to DNA damage.

Animals↗
PubMed1992

Structure of the human DNA ligase I gene.

The gene encoding DNA ligase I, the major DNA ligase activity in proliferating mammalian cells, maps to human chromosome 19q13.2-13.3. We have determined the complete structure of the gene, which is composed of 28 exons spanning 53kb on this chromosome. The first exon is untranslated, and utilises a GC dinucleotide instead of the canonical GT splice donor. The 5' flanking region lacks a TATA box and is highly GC-rich, as is characteristic of a 'housekeeping' gene. In common with the promoters of genes encoding other DNA replication enzymes, such as DNA polymerase alpha, the 5' flanking region of the DNA ligase I gene contains recognition elements for several transcription factors which may mediate increased expression in quiescent cells in response to growth factors.

Base Sequence↗
PubMed1992

Growth retardation and immunodeficiency in a patient with mutations in the DNA ligase I gene.

DNA ligases are required for the replication, repair, and recombination of DNA. A cell line derived from a young woman with growth retardation, sun sensitivity, and immunodeficiencies, who died aged 19 with lymphoma, showed two different miscoding mutations at the DNA ligase I locus on chromosome 19, one in each allele. One of the mutations was inherited from the mother and has also been detected in two healthy brothers. The patient had features similar to those of Bloom's syndrome (BS), but cell lines from BS patients do not have mutations in the DNA ligase I gene. This patient seems to represent a distinct genetic entity.

Cell Line↗
PubMed1992

Mutations in the DNA ligase I gene of an individual with immunodeficiencies and cellular hypersensitivity to DNA-damaging agents.

Two missense mutations occurring in different alleles of the DNA ligase I gene, encoding the major DNA ligase in proliferating mammalian cells, were detected in a human fibroblast strain (46BR). These cells exhibit retarded joining of Okazaki fragments during DNA replication and hypersensitivity to a variety of DNA-damaging agents. 46BR was derived from a patient who displayed symptoms of immunodeficiency, stunted growth, and sun sensitivity. A strongly reduced ability of DNA ligase I to form a labeled enzyme-adenylate intermediate correlated with the genetic defect in 46BR cells. The data indicate that human DNA ligase I is required for joining of Okazaki fragments during lagging-strand DNA synthesis and the completion of DNA excision repair.

Alleles↗
PubMed1992

Assignment of the gene encoding DNA ligase I to human chromosome 19q13.2-13.3.

The gene encoding DNA ligase I has been mapped on human chromosome 19 by analysis of rodent-human somatic cell hybrids informative for this chromosome and by two-color fluorescence in situ hybridization. The DNA ligase I gene (LIG1) is localized to 19q13.2-13.3 and is distal to ERCC1, the most telomeric of three DNA repair genes on this chromosome.

Blotting, Southern↗
PubMed1991

In vitro mutagenesis and functional expression in Escherichia coli of a cDNA encoding the catalytic domain of human DNA ligase I.

Human cDNAs encoding fragments of DNA ligase I, the major replicative DNA ligase in mammalian cells, have been expressed as lacZ fusion proteins in Escherichia coli. A cDNA encoding the carboxyl-terminal catalytic domain of human DNA ligase I was able to complement a conditional-lethal DNA ligase mutation in E. coli as measured by growth of the mutant strain at the non-permissive temperature. Targeted deletions of the amino and carboxyl termini of the catalytic domain identified a minimum size necessary for catalytic function and a maximum size for optimal complementing activity in E. coli. The human cDNA was subjected to systematic site-directed mutagenesis in vitro and mutant polypeptides assayed for functional expression in the E. coli DNA ligase mutant. Such functional analysis of the active site of DNA ligase I identified specific residues required for the formation of an enzyme-adenylate reaction intermediate.

Amino Acid Sequence↗