Population and high-risk approaches both necessary to reduce alcohol harm.
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Accidents, Traffic↗
Biomedical subjects
P Anderson
Publications and source records attributed to P Anderson.
The interaction between research and policy--alcohol and general practice in the United Kingdom.
Research evidence is considered for the effectiveness of screening for alcohol consumption in general practice and for the effectiveness of brief interventions in general practice. Evidence is then considered for the effectiveness of dissemination of brief interventions throughout general practice. The example of dissemination of smoking interventions is used as similar data is not yet available for alcohol. The structure of the UK contract for general practice is discussed and its relationship to research findings considered. Finally, future directions for both research and policy are highlighted.
Alcohol Drinking↗
The risk of alcohol.
We have reviewed 156 papers which provided sufficient information to relate individual alcohol consumption to risk for a variety of physical damage. Overall, there was evidence for a dose-response relationship between level of alcohol consumption and risk of harm for liver cirrhosis, cancers of the oropharynx, larynx, oesophagus, rectum (beer only), liver and breast, and blood pressure and stroke. An increased risk of cardiac arrhythmias, cardiomyopathy and sudden coronary death was associated with heavy drinking. There was evidence for a protective effect of alcohol consumption against risk of coronary heart disease, which could be achieved at consumption levels of less than 10 g alcohol a day. The mortality of non-drinkers was higher than that of moderate drinkers in some studies. Level of alcohol consumption and total mortality were dose-related when non-drinkers were excluded. The finding of a dose-relationship between alcohol and harm suggested causality. It was not possible to define individual risk for all harms at a given level of alcohol consumption because of variations in methodology, but some idea of the order of magnitude of the increased risk can be obtained from calculating trends of pooled log-odds ratios. At levels of alcohol consumption of more than 20-30 g a day, all individuals are likely to accumulate risk of harm. Current guidelines on upper limits of lower risk drinking in different countries (168-280 g of alcohol a week for men and 84-140 g a week for women) reflect levels at which the risk of total mortality is not greatly increased above one.
Alcohol Drinking↗
Histological evaluation of the effect of 0.05% tretinoin in the treatment of photo damaged skin. Geographic differences in elastosis in baseline biopsies.
In a randomised double-blind vehicle controlled trial of 0.05% tretinoin cream in the treatment of photodamaged skin, the histological results of paired biopsies from 28 individuals who applied tretinoin for 26 weeks are compared with 28 paired biopsies from a control group applying vehicle alone. There was a significant increase in epidermal thickness in the tretinoin-treated group (P < .001). Epidermal atrophy was reversed in ten patients applying tretinoin cream. Baseline biopsies obtained from participants in Melbourne, Victoria (38 degrees latitude) showed significantly less elastosis than those in Sydney (34 degrees latitude) and Newcastle in N.S.W., although the two groups did not show significant differences in age or sex, and the differences could not be correlated with skin type. Tretinoin cream had no effect on the degree of solar elastosis after 26 weeks application. Tretinoin cream appears effective in reversing epidermal atrophy and clinically diminishes fine wrinkling, mottled hyperpigmentation and skin roughness. Tretinoin cream may not offer a solution to the gross solar damage seen in the Australian population who have marked solar elastosis as a principal, clinical and histologic finding. However it is possible that dermal repair and reversal of solar elastosis may require topical application of tretinoin cream for a longer period than the six months used in this trial.
Administration, Topical↗
Site-selected insertion of the transposon Tc1 into a Caenorhabditis elegans myosin light chain gene.
We used the polymerase chain reaction to detect insertions of the transposon Tc1 into mlc-2, one of two Caenorhabditis elegans regulatory myosin light chain genes. Our goals were to develop a general method to identify mutations in any sequenced gene and to establish the phenotype of mlc-2 loss-of-function mutants. The sensitivity of the polymerase chain reaction allowed us to identify nematode populations containing rare Tc1 insertions into mcl-2. mlc-2::Tc1 mutants were subsequently isolated from these populations by a sib selection procedure. We isolated three mutants with Tc1 insertions within the mlc-2 third exon and a fourth strain with Tc1 inserted in nearby noncoding DNA. To demonstrate the generality of our procedure, we isolated two additional mutants with Tc1 insertions within hlh-1, the C. elegans MyoD homolog. All of these mutants are essentially wild type when homozygous. Despite the fact that certain of these mutants have Tc1 inserted within exons of the target gene, these mutations may not be true null alleles. All three of the mlc-2 mutants contain mlc-2 mRNA in which all or part of Tc1 is spliced from the pre-mRNA, leaving small in-frame insertions or deletions in the mature message. There is a remarkable plasticity in the sites used to splice Tc1 from these mlc-2 pre-mRNAs; certain splice sites used in the mutants are very different from typical eukaryotic splice sites.
Alleles↗
Scanning microradiographic study of the kinetics of subsurface demineralization in tooth sections under constant-composition and small constant-volume conditions.
The kinetics of subsurface demineralization of tooth sections has been studied in real-time by scanning microradiography (SMR). Demineralization was carried out: (1) with a large volume of solution buffered to pH = 4 to maintain a constant composition; and (2) in a small constant volume (approximately 3 mL), buffered initially at pH = 4, so that the degree of saturation at the tooth surface increased as the tooth dissolved. At constant composition, the change in lesion depth, Y, with time, T, followed a linear relation, Y = a + bT, for T > 44 +/- 5 h. Before this time, the relation could be approximated by a linear one with different a and b constants. At constant volume, Y = q(1-e-r(T + s)) for all T, where q, r and s are constants. Similar relations, with different constants, were found for the mineral loss per unit area of lesion exposed to acid. These results showed that the process of demineralization under the rather severe conditions used was essentially a surface-controlled process. The change of slope at approximately 44 h and the presence of the constant s in the exponential function were attributed to a change in kinetics after formation of the surface layer.
Dental Enamel↗
The home care alternative: a cancer survivor's story.
The difference that home care makes in the life of a cancer patient is communicated most strongly by an individual survivor. A social worker recalls her positive home cancer treatment and describes her quest to help others travel the same path.
Adult↗
Dive into waste reduction: start by buying smart.
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Conservation of Natural Resources↗
Management of large-scale disasters.
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Disaster Planning↗
Effectiveness of general practice interventions for patients with harmful alcohol consumption.
Harmful alcohol consumption can have severe consequences for both the individual and society. A review of the six published studies on the effectiveness of general practitioner interventions for individuals with harmful alcohol consumption suggests that between five and 10 minutes of advice leads to reductions of alcohol consumption of around 25-35% at follow up six months or one year later. Two of the three studies which failed to demonstrate an intervention effect had inadequate sample sizes and in two of the studies the control group was a comparison group which received minimal advice to reduce alcohol consumption. There was greater evidence for an intervention effect among men than women. The methodological problems of the studies are discussed.
Alcohol Drinking↗
Cytotoxic potential of intraepithelial lymphocytes (IELs). Presence of TIA-1, the cytolytic granule-associated protein, in human IELs in normal and diseased intestine.
Human intestinal intraepithelial lymphocytes (IELs) have phenotypic characteristics of cytotoxic T cells, yet a cytotoxic function has not been demonstrated in redirected lysis assays. A monoclonal antibody that reacts with a cytotoxic granule-associated protein, TIA-1, was used in this study to identify this protein in many, but not all, IELs of normal human proximal small intestine. Furthermore, in active celiac disease, in which the number of IELs is significantly increased, a corresponding increase in the number of TIA-1 cells was found. These results indicate that whereas cytotoxicity of human IELs has been difficult to demonstrate, they contain at least one of the proteins associated with cytotoxicity, and a failure to demonstrate this function may be related to the in vitro assay system used.
CD3 Complex↗
Management of alcohol problems: the role of the general practitioner.
Some 23% of men and 8% of women in the United Kingdom are consuming alcohol at levels that are of risk to their health, or are experiencing some problems related to their alcohol use. Traditionally, general practitioner efforts have focused on diagnosing and treating patients with a substantial history of dependence, and relatively little attention has been given to early intervention, with at-risk drinkers identified in general practice through screening or case finding programmes. Evidence indicates that early interventions by general practitioners are effective in reducing alcohol consumption among at-risk patients. Further work is still needed on the most effective ways of supporting general practitioners in this task.
Alcohol Drinking↗
Infection of human natural killer (NK) cells with replication-defective human T cell leukemia virus type I provirus. Increased proliferative capacity and prolonged survival of functionally competent NK cells.
Human T-cell leukemia virus type I (HTLV-I) can infect a variety of human cell types, but only T lymphocytes are efficiently immortalized after HTLV-I infection. This study reports an attempt to infect and to immortalize NK cells with HTLV-I. Co-cultivation of freshly isolated NK cells with a HTLV-I-producing T cell line did not result in NK cell infection. However, NK cells activated with an anti-CD16 mAb and co-cultivated with a HTLV-I-producing T cell line were reproducibly infected by HTLV-I. HTLV-I infection was documented in NK cell lines and clones by the detection of defective integrated provirus by both Southern blot and polymerase chain reaction analysis. Although HTLV-I-infected NK cells produced viral proteins, they did not produce infectious viral particles. HTLV-I-infected NK cells were phenotypically indistinguishable from their uninfected counterparts (CD16+, CD2+, CD56+, CD3-). They also retained the ability to mediate both natural and antibody-dependent cell cytotoxicity. The IL-2-dependent proliferation of HTLV-I-infected NK cells was significantly greater than that of uninfected NK cells. The doubling time of this infected population was reduced from 9 days to 3 days, and the overall survival of the culture in the absence of restimulation was extended from 5 wk to 18 wk. Unlike T lymphocytes, HTLV-I-infected NK cells were not immortal, implying a fundamental difference between these two lymphocyte populations.
Base Sequence↗
Scotland. 2001: a space-saving odyssey.
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Catchment Area, Health↗
Identification and functional characterization of a TIA-1-related nucleolysin.
We recently reported the molecular cloning of a cytotoxic granule-associated RNA-binding protein designated TIA-1. The ability of recombinant TIA-1 to induce DNA fragmentation in permeabilized cells suggested that this protein is the granule component responsible for inducing apoptosis in cytolytic lymphocyte (CTL) targets. Here we report the characterization of a cDNA encoding a TIA-1-related protein designated TIAR. The deduced amino acid sequence of TIAR reveals it to be a 42-kDa protein possessing three RNA-binding domains and a carboxyl-terminal auxiliary domain. Although the RNA-binding domains of TIA-1 and TIAR share greater than 85% amino acid homology, their carboxyl-terminal auxiliary domains are only 51% homologous. The carboxyl terminus of TIAR contains a lysosome-targeting motif, indicating that TIAR is probably a cytotoxic granule-associated protein. Like TIA-1, purified recombinant TIAR induced DNA fragmentation in permeabilized target cells. Although immunoblotting analysis of post-nuclear supernatants revealed TIA-1 protein to be restricted to CTLs, PCR analysis revealed the expression of TIA-1 and TIAR mRNA transcripts in a wide variety of cell types. Our data suggest that the granules of CTLs contain at least two candidate nucleolysins involved in CTL killing.
Amino Acid Sequence↗
Chemical synthesis of RNA using fast oligonucleotide deprotection chemistry.
The exocyclic amine protecting groups in oligonucleotide synthesis which require 8-16 hours at 55 degrees C for deprotection in ammonia have been replaced with more labile base protecting groups (dimethylformamidine for adenine and guanine and isobutyryl for cytosine). Using these fast oligonucleotide deprotecting groups which require 2-3 hours at 55 degrees C for complete deprotection, a new set of cyanoethyl phosphoramidite ribonucleoside monomers and supports has been developed. Ribozymes and substrate RNAs which were synthesized with these phosphoramidites were assayed and were found to have full catalytic (biological) activity.
Base Sequence↗
The effect of endothelin 1 on the retinal microvascular pericyte.
The effect of the highly vasoactive peptide endothelin 1 (ET1) was tested on bovine retinal microvascular pericytes propagated in vitro. Specific binding of 125I-ET1 to retinal pericytes was documented by autoradiography. ET1 caused contraction of pericytes at a concentration of 0.1 nM which was accompanied by increases in inositol phosphates. Exposure of pericytes to 10 nM ET1 resulted in the aggregation and realignment of muscle-specific actins into bundles which were oriented parallel to the long axis of the cell, and ET1 was also mitogenic to pericytes in the presence of low levels of fetal calf serum. These observations suggest that ET1 may play an important role in endothelial cell-pericyte interactions within the microvasculature of the retina and that it may be involved in the autoregulation of retinal blood flow.
Actins↗
High molecular weight proteins in the nematode C. elegans bind [3H]ryanodine and form a large conductance channel.
Single-channel properties of a polypeptide fraction from the nematode Caenorhabditis elegans highly enriched in binding sites were studied in planar bilayers. [3H]Ryanodine binding sites were purified by sucrose gradient centrifugation of C. elegans microsomes solubilized in CHAPS detergent. The highest [3H]ryanodine binding activity sedimented at approximately 18% sucrose (wt/vol), and was composed of a major polypeptide with a M(r) of 360,000 and a minor polypeptide with a M(r) of 170,000. The ryanodine-binding polypeptide(s) formed a Ca(2+)-permeable channel with a permeability ratio P(divalent)/P(monovalent) = 4 and two conductance states of 215 pS and 78 pS in 0.25 M KCl. Ryanodine locked the channel in the 78 pS state and inhibited transitions between the 215 pS and 78 pS states. These data demonstrated the presence of a ryanodine receptor in C. elegans with functional properties comparable to those described in mammalian muscle.
Animals↗