Patient safety and ophthalmic surgery marking: which side are you on?
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Clinical Competence↗
Biomedical subjects
M M White
Publications and source records attributed to M M White.
Adolescent smoking decline during California's tobacco control programme.
OBJECTIVE: California's comprehensive tobacco control programme was 13 years old in 2002; by then, children entering adolescence at the start of the programme were young adults. This study examines whether adolescent smoking declined over this period, whether any decline carried through to young adulthood, and whether it was specific to California. SETTING AND PARTICIPANTS: Most data were from the 1990-2002 California Tobacco Surveys (CTS) (adolescents 12-17 years, > 5000/survey, young adults 18-24 years, > 1000/survey). Additional data were from the national 1992/93-2001/02 Current Population Survey (CPS) (young adults 18-24 years, > 15,000/survey). RESULTS: Over the 13 year period in California, ever puffing declined by 70% in 12-13 year olds, by 53% in 14-15 year olds from 1992-2002, and by 34% in 16-17 year olds from 1996-2002 (CTS). As noted, the decline commenced progressively later in each older group. Smoking experimentation (1+ cigarettes) and established smoking (> 100 cigarettes in lifetime) showed similar patterns. Compared to 1990, the percentage of California young adults (CTS data) who ever experimented declined by 14%, with half of the decline from 1999-2002. CPS young adult smoking prevalence (established and now smoke everyday or some days) was constant in the rest of the USA over the entire period, but California showed a recent 18% decline from 1998/99 to 2001/02. CONCLUSIONS: California's comprehensive programme may have kept new adolescent cohorts from experimenting with cigarettes. Low young adolescent experimentation rates at programme start appeared to carry through to young adulthood, resulting in a recent drop in young adult smoking prevalence in California not observed in the rest of the USA.
Adolescent↗
Radioactive waste disposal implications of extending Part IIA of the Environmental Protection Act to cover radioactively contaminated land.
A short study has been carried out of the potential radioactive waste disposal issues associated with the proposed extension of Part IIA of the Environmental Protection Act 1990 to include radioactively contaminated land, where there is no other suitable existing legislation. It was found that there is likely to be an availability problem with respect to disposal at landfills of the radioactive wastes arising from remediation. This is expected to be principally wastes of high volume and low activity (categorised as low level waste (LLW) and very low level waste (VLLW)). The availability problem results from a lack of applications by landfill operators for authorisation to accept LLW wastes for disposal. This is apparently due to perceived adverse publicity associated with the consultation process for authorisation coupled with uncertainty over future liabilities. Disposal of waste as VLLW is limited both by questions over volumes that may be acceptable and, more fundamentally, by the likely alpha activity of wastes (originating from radium and thorium operations). Authorised on-site disposal has had little attention in policy and guidance in recent years, but may have a part to play, especially if considered commercially attractive. Disposal at BNFL's near surface disposal facility for LLW at Drigg is limited to wastes for which there are no practical alternative disposal options (and preference has been given to operational type wastes). Therefore, wastes from the radioactively contaminated land (RCL) regime are not obviously attractive for disposal to Drigg. Illustrative calculations have been performed based on possible volumes and activities of RCL arisings (and assuming Drigg's future volumetric disposal capacity is 950,000 m3). These suggest that wastes arising from implementing the RCL regime, if all disposed to Drigg, would not represent a significant fraction of the volumetric capacity of Drigg, but could have a significant impact on the radiological capacity with respect to 226Ra plus 232Th. The government's decision-making programme for managing solid radioactive wastes in the UK may possibly achieve a general consensus that the use of landfill for LLW from the RCL regime has a fundamental role to play. However, this is unlikely to change the situation within the next few years. No new national facility arising from this programme is likely to be available during the first decade of the operation of a new RCL regime. Hence it appears that Drigg will need to play an important role for some years to come.
Humans↗
Role of in vitro cholesterol depletion in mediating human platelet aggregation.
We investigated the direct role of cholesterol lowering on human platelet aggregation by in vitro cholesterol depletion using methyl-beta-cyclodextrin. Collagen and thrombin receptor agonist peptide induced maximal aggregation was significantly decreased in cholesterol depleted platelets. In contrast, anti-CD9 antibody, mAb7, or anti-beta(3) antibody, D3, induced percent maximal aggregation was unaffected by cholesterol depletion. Surface and total alpha(IIb)beta(3) levels were equivalent in both groups. Morphological and ultrastructural analysis of collagen induced aggregates revealed that normal and cholesterol depleted platelets changed shape and aggregated; however, cholesterol depletion impaired microtubule ring formation and aggregate size. Cholesterol depletion also diminished the extent of the open canalicular system and collagen induced platelet ATP release. These data suggest cholesterol depletion impairs platelet aggregation by altering platelet ultrastructure critical in mediating secretion. Temporal differences and differences in tyrosine phosphoprotein levels following collagen stimulation were observed, thereby indicating that platelet signaling was concurrently affected by cholesterol depletion.
Adenosine Triphosphate↗
Was there significant tax evasion after the 1999 50 cent per pack cigarette tax increase in California?
OBJECTIVES: Several states, including California, have implemented large cigarette excise tax increases, which may encourage smokers to purchase their cigarettes in other lower taxed states, or from other lower or non-taxed sources. Such tax evasion thwarts tobacco control objectives and may cost the state substantial tax revenues. Thus, this study investigates the extent of tax evasion in the 6-12 months after the implementation of California's 0.50 dollars/pack excise tax increase. DESIGN AND SETTING: Retrospective data analysis from the 1999 California Tobacco Surveys (CTS), a random digit dialled telephone survey of California households. MAIN OUTCOME MEASURES: Sources of cigarettes, average daily cigarette consumption, and reported price paid. RESULTS: Very few (5.1 (0.7)% (+/-95% confidence limits)) of California smokers avoided the excise tax by usually purchasing cigarettes from non- or lower taxed sources, such as out-of-state outlets, military commissaries, or the internet. The vast majority of smokers purchased their cigarettes from the most convenient and expensive sources: convenience stores/gas (petrol) stations (45.0 (1.9)%), liquor/drug stores (16.4 (1.6)%), and supermarkets (8.8 (1.2)%). CONCLUSIONS: Despite the potential savings, tax evasion by individual smokers does not appear to pose a serious threat to California's excise tax revenues or its tobacco control objectives.
Adolescent↗
Does cigarette price influence adolescent experimentation?
The economics literature generally agrees that state and federal excise taxes can play an important role in deterring adolescent smoking. Teens' apparent responsiveness to cigarette prices is puzzling, since the majority of adolescent smokers do not buy their cigarettes. Teens typically do not begin to purchase cigarettes until they have developed an established pattern of smoking. Previous studies have not had adequate measures of smoking experience to explore whether adolescents' price responsiveness may vary by smoking experience. This paper uses data from a 1993 national survey of youth smoking to explore this hypothesis.
Adolescent↗
Active GPIIb-IIIa conformations that link ligand interaction with cytoskeletal reorganization.
Glycoprotein (GP) IIb-IIIa plays a critical role in platelet aggregation and platelet-mediated clot retraction. This study examined the intramolecular relationship between GPIIb-IIIa activation and fibrinogen binding, platelet aggregation, and platelet-mediated clot retraction. To distinguish between different high-affinity activation states of GPIIb-IIIa, the properties of an antibody (D3) specific for GPIIIa that induces GPIIb-IIIa binding to adhesive protein molecules and yet completely inhibits clot retraction were used. Clot retraction inhibition by D3 was not due to altered platelet-fibrin interaction; however, combination treatments of D3 and adenosine diphosphate (ADP) inhibited full-scale aggregation and decreased the amounts of GPIIb-IIIa and talin incorporated into the core cytoskeletons. Morphologic evaluation of the D3/ADP aggregates showed platelets that were activated but to a lesser extent when compared to ADP only. ADP addition to platelets caused an increase in the number of D3 binding sites indicating that ligand had bound to the GPIIb-IIIa receptor. These data suggest that high-affinity GPIIb-IIIa- mediated ligand binding can be separated mechanistically from GPIIb-IIIa-mediated clot retraction and that clot retraction requires additional signaling through GPIIb-IIIa after ligand binding. The conformation recognized by D3 represents the expression of a GPIIb-IIIa activation state that participates in full-scale platelet aggregation, cytoskeletal reorganization, and clot retraction.
Adenosine Diphosphate↗
Association between household and workplace smoking restrictions and adolescent smoking.
CONTEXT: Recent marked increases in adolescent smoking indicate a need for new prevention approaches. Whether workplace and home smoking restrictions play a role in such prevention is unknown. OBJECTIVE: To assess the association between workplace and home smoking restrictions and adolescent smoking. DESIGN, SETTING, AND SUBJECTS: Data were analyzed from 2 large national population-based surveys, the Current Population Surveys of 1992-1993 and 1995-1996, which included 17,185 adolescents aged 15 to 17 years. MAIN OUTCOME MEASURES: Smoking status of the adolescents surveyed, compared by presence of home and workplace smoking restrictions. RESULTS: After adjusting for demographics and other smokers in the household, adolescents who lived in smoke-free households were 74% (95% confidence interval [CI], 62%-88%) as likely to be smokers as adolescents who lived in households with no smoking restrictions. Similarly, adolescents who worked in smoke-free workplaces were 68% (95% CI, 51%-90%) as likely to be smokers as adolescents who worked in a workplace with no smoking restrictions. Adolescent smokers were 1.80 (95% CI, 1.23-2.65) times more likely to be former smokers if they lived in smoke-free homes. The most marked relationship of home smoking restrictions to current adolescent smoking occurred in households where all other members were never-smokers. Current smoking prevalence among adolescents in homes without smoking restrictions approached that among adolescents in homes with a current smoker but with smoking restrictions. CONCLUSIONS: Parents with minor children should be encouraged to adopt smoke-free homes. Smoke-free workplaces can also augment smoking prevention. These findings emphasize the importance of tobacco control strategies aimed at the entire population rather than at youth alone. JAMA. 2000;284:717-722
Adolescent↗
Acetylcholine receptor gating is influenced by the polarity of amino acids at position 9' in the M2 domain.
Ligand-gated ion channels contain a conserved leucine at position 9' (L9') in the M2 transmembrane domain. We used multiple substitutions at this position in the gamma subunit of the mouse acetylcholine receptor (AChR) (gammaL9') to examine the role of residue polarity at this position in the gating process at both the macroscopic and single-channel levels. The midpoint of the macroscopic dose-response relationship (EC(50)) and the channel closing rate constant, alpha, decreased as the polarity of the residue at that position increased, suggesting a stabilization of the open state of the channel. Both parameters showed similar dependencies on the polarity of the substituted residue. These data support the notion that during AChR gating, the amino acid at the 9' position moves into a polar environment, and that interactions between this residue and the polar environment determine the stability of the open state. Since this residue is conserved in all other members of the ligand-gated ion channel family, we suggest that a similar mechanism applies to the other members of the family.
Amino Acid Substitution↗
Forskolin modulates acetylcholine receptor gating by interacting with the small extracellular loop between the M2 and M3 transmembrane domains.
1. Forskolin acts as an allosteric modulator of muscle-type nicotinic acetylcholine receptors. Receptors from mouse muscle and Torpedo electroplax demonstrate differential sensitivity to inhibition by forskolin. Previous work from this laboratory suggested that the gamma subunit is responsible for this differential sensitivity. 2. We have used a series of mouse/Torpedo species-chimeric gamma subunits to further define the site of forskolin interaction with the gamma subunit. Analysis of the patterns of forskolin inhibition of receptors containing mouse/Torpedo chimeric gamma subunits along with the mouse alpha, beta, and delta subunits suggests that forskolin interacts with the small extracellular domain that links the M2 and M3 transmembrane domains (the M2-M3 linker). 3. We suggest that the M2-M3 linker domain plays an important role in the transduction of ligand binding to the conformational changes that result in channel opening.
Allosteric Regulation↗
Perceptions of children who lie: influence of lie motive and benefit.
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Attitude↗
Copepod development rates in relation to genome size and 18S rDNA copy number.
It is known that body sizes and temperature-independent developmental durations within two genera of calanoid Copepoda (Crustacea) are positively related to nuclear DNA contents of their somatic nuclei. Evidently because of the constraint of similar cell numbers among the species, (nucleotypic) effects of nucleus size on cell size and on cell-level processes are expressed at the whole-organism level. Here, we show that developmental durations of eight species of five genera are also negatively related to their greatly differing numbers of 18S rRNA genes per unit DNA. We propose that levels of rDNA iteration among copepods have been controlled by natural selection to regulate ribosome concentrations, therefore protein production and development rates, independently of the large variations in genome sizes, which are in turn adapted to regulating cell and therefore body sizes.
Animals↗
Chronic hypoxia, pregnancy, and endothelium-mediated relaxation in guinea pig uterine and thoracic arteries.
Vasodilation that occurs during normal pregnancy is associated with enhanced relaxation and decreased contractile response to agonists, which are in part due to increased stimulated and basal nitric oxide (NO). In preeclampsia and/or pregnancies carried at high altitude (HA), this normal vascular adjustment is reversed or diminished. We previously reported that HA exposure did not inhibit the pregnancy-associated decrease in contractile response to agonist or basal NO in guinea pig uterine arteries (UA). We therefore sought to determine whether altitude interfered with effects of pregnancy on endothelium-dependent relaxation through a reduction in stimulated NO. We examined the relaxation response to ACh in UA and bradykinin in thoracic arteries (TA) and effects of NO inhibition with 200 microM N(G)-nitro-L-arginine (L-NNA) in arterial rings isolated from nonpregnant and pregnant guinea pigs exposed throughout gestation to low altitude (LA, 1,600 m, n = 26) or HA (3,962 m, n = 22). In pregnant UA, relaxation to ACh was enhanced (P < 0.05) at both altitudes and NO inhibition diminished, but did not reverse, ACh relaxation. The effect of L-NNA on the relaxation response to ACh was less in HA than in LA animals (P = 0.0021). In nonpregnant UA, relaxation to ACh was similar in LA and HA animals. L-NNA reversed the relaxation response to ACh at HA but not at LA. In TA, relaxation to bradykinin was unaltered by pregnancy or altitude and was completely reversed by NO inhibition. These data suggest that effects of NO inhibition are diminished in UA during pregnancy at HA. Additional studies are needed to confirm whether these effects are mediated through inhibition of stimulated NO. HA exposure did not inhibit relaxation to ACh, perhaps because of stimulation of other vasodilators.
Altitude↗
Effects of clomipramine hydrochloride on dominance-related aggression in dogs.
OBJECTIVE: To compare effects of the serotonergic drug clomipramine hydrochloride with those of placebo for treatment of dominance-related aggression in dogs. DESIGN: Randomized, placebo-controlled, double-blind clinical trial. ANIMALS: 28 neutered dogs > 1 year old with dominance-related aggression. PROCEDURE: Dogs displaying > or = 3 aggressive episodes/wk toward > or = 1 human family member in response to identifiable behavioral triggers were included in the study. Owners were instructed not to change patterns of interaction with their dogs during the study. After 2 weeks of baseline observations, dogs were treated for 6 weeks with clomipramine (1.5 mg/kg [0.7 mg/lb] of body weight, q 12 h; n = 15) or placebo (13). Responses to triggers were assigned the following aggression scores: no response, 0; growl or lip curl, 1; snap or bite, 2. Mean scores for responses to triggers were obtained during the 2-week pretreatment period (baseline) and during the first and second weeks, third and fourth weeks, and fifth and sixth weeks of treatment. At the end of the study, owners assigned a score designed to evaluate their overall perceived change in aggressiveness; this was referred to as the global score. RESULTS: Mean aggression scores decreased at the fifth and sixth week of treatment in both groups, compared with baseline scores. However, mean scores between groups were not different. Global scores, assigned by the owner, generally reflected changes in mean aggression scores. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with placebo, clomipramine administered to dogs at the dosage recommended for treatment of separation anxiety did not reduce aggressiveness toward human family members.
Aggression↗
Structural features of the ligand-binding domain of the serotonin 5HT3 receptor.
The nicotinic acetylcholine receptor (AChR) and the serotonin type 3 receptor (5HT3R) are members of the ligand-gated ion channel gene family. Both receptors are inhibited by nanomolar concentrations of d-tubocurarine (curare) in a competitive fashion. Chemical labeling studies on the AChR have identified tryptophan residues on the gamma (gammaTrp-55) and delta (deltaTrp-57) subunits that interact with curare. Comparison of the sequences of these two subunits with the 5HT3R shows that a tryptophan residue is found in the homologous position in the 5HT3R (Trp-89), suggesting that this residue may be involved in curare-5HT3R interactions. Site-directed mutagenesis at position Trp-89 markedly reduces the affinity of the 5HT3R for the antagonists curare and granisetron but has little effect on the affinity for the agonist serotonin. To further examine the role of this region of the receptor in ligand-receptor interactions, alanine-scanning mutagenesis analysis of the region centered on Trp-89 (Thr-85 to Trp-94) was carried out, and the ligand binding properties of the mutant receptors were determined. Within this region of the receptor, curare affinity is reduced by substitution only at Trp-89, whereas serotonin affinity is reduced only by substitution at Arg-91. On the other hand, granisetron affinity is reduced by substitutions at Trp-89, Arg-91, and Tyr-93. This differential effect of substitutions on ligand affinity suggests that different ligands may have different points of interaction within the ligand-binding pocket. In addition, the every-other-residue periodicity of the effects on granisetron affinity strongly suggests that this region of the ligand-binding site of the 5HT3R (and by inference, other members of the ligand-gated ion channel family) is in a beta-strand conformation.
Amino Acid Sequence↗
How adolescents get their cigarettes: implications for policies on access and price.
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Adolescent↗
A CD9, alphaIIbbeta3, integrin-associated protein, and GPIb/V/IX complex on the surface of human platelets is influenced by alphaIIbbeta3 conformational states.
A noncovalently associated complex comprising of CD9, the fibrinogen (Fg) receptor alphaIIbbeta3, integrin-associated protein (IAP), and glycoprotein (GP) Ib/V/IX complex was isolated from Chaps-solubilized human platelets. The CD9 complex was immunoprecipitated by mAbs specific for CD9 (mAb7), IAP (BRIC126), GPIb (SZ1), GPIX (GR-P), beta3 (AP3) and alphaIIb (C3). Additionally, the association between CD9 and alphaIIbbeta3 was demonstrated by ELISA. In this system, CD9 did not bind to vitronectin receptor (alphavbeta3) suggesting that CD9/alphaIIbbeta3 association was alphaIIb-subunit or alphaIIbbeta3-complex dependent. D3, an alphaIIbbeta3-activating mAb that is also an anti-LIBS (ligand-induced binding site), immunoprecipitated primarily alphaIIbbeta3 with GPIb and IAP. CD9 was not detected in D3 immunoprecipitates. D3 binding induced platelet aggregation via direct alphaIIbbeta3 activation and was upregulated by the alphaIIbbeta3 antagonist eptifibatide. In contrast, AP3 and C3 exhibited neither effect. In addition, D3 also inhibited whole blood clot retraction, in contrast to AP3 and C3, suggesting that conformational constraints on alphaIIbbeta3 by D3 binding not only influenced the CD9 complex but also affected alphaIIbbeta3 post receptor occupancy events. The CD9 complex was immunoprecipitated in the presence of eptifibatide, demonstrating that alphaIIbbeta3 receptor occupancy was not sufficient to cause complex dissociation. CD9 complex isolation was also independent of platelet activation, although a twofold increase in the quantity of CD9 complex was seen after platelet activation by alpha-thrombin in the presence of CaCl2 compared with that present in EDTA. Stirred platelets showed fibrinogen-mediated aggregation by alpha-thrombin in the presence of CaCl2 but not with EDTA, suggesting that fibrinogen crosslinking of CD9 complexes via alphaIIbbeta3 could be partially responsible for this increase. These findings imply that the platelet CD9 complex is independent of platelet activation although it is dependent upon the conformation state of alphaIIbbeta3.
Antibodies, Monoclonal↗
Home smoking restrictions: which smokers have them and how they are associated with smoking behavior.
Home smoking restrictions have primarily been promoted as a means of protecting non-smokers from secondhand tobacco smoke. However, research suggests that smokers who live in smoke-free homes may modify their smoking behavior. Population-based survey data from California (n = 8904) were used to confirm this association and to examine demographic and social characteristics of smokers who reported home smoking restrictions. Report of a recent quit attempt and intention to quit were associated with family preference that the smoker not smoke, with home smoking restrictions appearing to be a concrete expression of this social pressure. In contrast, light smoking (< 15 cigarettes/day) was negatively related to family preference (light smokers may not offend non-smokers) but very positively related to the level of home smoking restrictions. Additionally, smoke-free homes appear to prolong time to relapse following cessation. Male smokers were more likely than females to report smoke-free homes, and such reports decreased with age. While Hispanics and Asians were more likely to report smoke-free homes than Non-Hispanic whites, African Americans were less likely to report them. After adjusting for demographics, smokers were nearly 6 times more likely to report smoke-free homes if they lived with a non-smoking adult and child compared to when there was no child or adult non-smoker in the household, and over 5 times more likely to report a smoke-free home if they believed in the harmfulness of secondhand smoke. Tobacco Control efforts to promote smoke-free homes may give family members leverage to encourage smokers to quit, and to modify smokers' behavior in ways that would help them quit and stay quit.
Actuarial Analysis↗