bluuebunny/crossref_metadata_2025 huggingface dataset:
Potassium Channels as Targets for Therapeutic Intervention
Authors: Garcia Maria L. , Kaczorowski Gregory J.
Published: September 2005

The potassium channel superfamily presents a rich source of targets for therapeutic intervention. Indeed, the development of specific potassium channel modulators could lead to the effective treatment of various diseases for which current therapies are clearly suboptimal. Numerous factors play a role in determining whether the successful clinical development of such drugs can ever be achieved. However, the large body of information accumulated over the last few years on the structure and function of potassium channels is expected to drive drug-development efforts in the pharmaceutical industry on these targets, with the ultimate goal of developing therapies that will improve patient quality of life.
Myxoxanthophyll Is Required for Normal Cell Wall Structure and Thylakoid Organization in the Cyanobacterium
Synechocystis
sp. Strain PCC 6803
Authors: Mohamed Hatem E. , van de Meene Allison M. L. , Roberson Robert W. , Vermaas Wim F. J.
Published: September 2005

Myxoxanthophyll is a carotenoid glycoside in cyanobacteria that is of unknown biological significance. The sugar moiety of myxoxanthophyll in
Synechocystis
sp. strain PCC 6803 was identified as dimethyl fucose. The open reading frame sll1213 encoding a fucose synthetase orthologue was deleted to probe the role of fucose and to determine the biological significance of myxoxanthophyll in
Synechocystis
sp. strain PCC 6803. Upon deletion of sll1213, a pleiotropic phenotype was obtained: when propagated at 0.5 μmol photons m
−2
s
−1
, photomixotrophic growth of cells lacking sll1213 was poor. When grown at 40 μmol photons m
−2
s
−1
, growth was comparable to that of the wild type, but cells showed a severe reduction in or loss of the glycocalyx (S-layer). As a consequence, cells aggregated in liquid as well as on plates. At both light intensities, new carotenoid glycosides accumulated, but myxoxanthophyll was absent. New carotenoid glycosides may be a consequence of less-specific glycosylation reactions that gained prominence upon the disappearance of the native sugar moiety (fucose) of myxoxanthophyll. In the mutant, the N-storage compound cyanophycin accumulated, and the organization of thylakoid membranes was altered. Altered cell wall structure and thylakoid membrane organization and increased cyanophycin accumulation were also observed for Δslr0940K, a strain lacking ζ-carotene desaturase and thereby all carotenoids but retaining fucose. Therefore, lack of myxoxanthophyll and not simply of fucose results in most of the phenotypic effects described here. It is concluded that myxoxanthophyll contributes significantly to the vigor of cyanobacteria, as it stabilizes thylakoid membranes and is critical for S-layer formation.
Vibrio vulnificus
Secretes a Broad-Specificity Metalloprotease Capable of Interfering with Blood Homeostasis through Prothrombin Activation and Fibrinolysis
Authors: Chang Alan K. , Kim Hyo Young , Park Jung Eun , Acharya Pankaj , Park Il-Seon , Yoon Seong Myeong , You Ho Jin , Hahm Kyung-Soo , Park Jong Kun , Lee Jung Sup
Published: September 2005

Vibrio vulnificus
is a causative agent of serious food-borne diseases in humans related to the consumption of raw seafood. It secretes a metalloprotease that is associated with skin lesions and serious hemorrhagic complications. In this study, we purified and characterized an extracellular metalloprotease (designated as vEP) having prothrombin activation and fibrinolytic activities from
V. vulnificus
ATCC 29307. vEP could cleave various blood clotting-associated proteins such as prothrombin, plasminogen, fibrinogen, and factor Xa, and the cleavage could be stimulated by addition of 1 mM Mn
2+
in the reaction. The cleavage of prothrombin produced active thrombin capable of converting fibrinogen to fibrin. The formation of active thrombin appeared to be transient, with further cleavage resulting in a loss of activity. The cleavage of plasminogen, however, did not produce an active plasmin. vEP could cleave all three major chains of fibrinogen without forming a clot. It could cleave fibrin polymer formed by thrombin as well as the cross-linked fibrin formed by factor XIIIa. In addition, vEP could also cleave plasma proteins such as bovine serum albumin and gamma globulin, and its broad specificity is reflected in the cleavage sites, which include Asp
207
-Phe
208
and Thr
272
-Ala
273
bonds in prothrombin and a Tyr
80
-Leu
81
bond in plasminogen. Taken together, the data suggest that vEP is a broad-specificity protease that could function as a prothrombin activator and a fibrinolytic enzyme to interfere with blood homeostasis as part of the mechanism associated with the pathogenicity of
V. vulnificus
in humans and thereby facilitate the development of systemic infection.
WOR5, a Novel Tungsten-Containing Aldehyde Oxidoreductase from
Pyrococcus furiosus
with a Broad Substrate Specificity
Authors: Bevers Loes E. , Bol Emile , Hagedoorn Peter-Leon , Hagen Wilfred R.
Published: September 2005

WOR5 is the fifth and last member of the family of tungsten-containing oxidoreductases purified from the hyperthermophilic archaeon
Pyrococcus furiosus
. It is a homodimeric protein (subunit, 65 kDa) that contains one [4Fe-4S] cluster and one tungstobispterin cofactor per subunit. It has a broad substrate specificity with a high affinity for several substituted and nonsubstituted aliphatic and aromatic aldehydes with various chain lengths. The highest catalytic efficiency of WOR5 is found for the oxidation of hexanal (
V
max
= 15.6 U/mg,

K
m

= 0.18 mM at 60°C). Hexanal-incubated enzyme exhibits
S
= 1/2 electron paramagnetic resonance signals from [4Fe-4S]
1+
(
g
values of 2.08, 1.93, and 1.87) and W
5+
(
g
values of 1.977, 1.906, and 1.855). Cyclic voltammetry of ferredoxin and WOR5 on an activated glassy carbon electrode shows a catalytic wave upon addition of hexanal, suggesting that ferredoxin can be a physiological redox partner. The combination of WOR5, formaldehyde oxidoreductase, and aldehyde oxidoreductase forms an efficient catalyst for the oxidation of a broad range of aldehydes in
P. furiosus
.
Global Transcriptome Analysis ofShewanella oneidensisMR-1 Exposed to Different Terminal Electron Acceptors
Authors: Beliaev A. S. , Klingeman D. M. , Klappenbach J. A. , Wu L. , Romine M. F. , Tiedje J. M. , Nealson K. H. , Fredrickson J. K. , Zhou J.
Published: September 2005

To gain insight into the complex structure of the energy-generating networks in the dissimilatory metal reducerShewanella oneidensisMR-1, global mRNA patterns were examined in cells exposed to a wide range of metal and non-metal electron acceptors. Gene expression patterns were similar irrespective of which metal ion was used as electron acceptor, with 60% of the differentially expressed genes showing similar induction or repression relative to fumarate-respiring conditions. Several groups of genes exhibited elevated expression levels in the presence of metals, including those encoding putative multidrug efflux transporters, detoxification proteins, extracytoplasmic sigma factors and PAS-domain regulators. Only one of the 42 predictedc-type cytochromes in MR-1, SO3300, displayed significantly elevated transcript levels across all metal-reducing conditions. Genes encoding decaheme cytochromes MtrC and MtrA that were previously linked to the reduction of different forms of Fe(III) and Mn(IV), exhibited only slight decreases in relative mRNA abundances under metal-reducing conditions. In contrast, specific transcriptome responses were displayed to individual non-metal electron acceptors resulting in the identification of unique groups of nitrate-, thiosulfate- and TMAO-induced genes including previously uncharacterized multi-cytochrome gene clusters. Collectively, the gene expression results reflect the fundamental differences between metal and non-metal respiratory pathways ofS. oneidensisMR-1, where the coordinate induction of detoxification and stress response genes play a key role in adaptation of this organism under metal-reducing conditions. Moreover, the relative paucity and/or the constitutive nature of genes involved in electron transfer to metals is likely due to the low-specificity and the opportunistic nature of the metal-reducing electron transport pathways.
Ab initio Correlation Effects in Density Functional Theories: An Electron-Distribution-Based Study for Neon
Authors: Jankowski Karol , Grabowski Ireneusz , Nowakowski Krzysztof , Wasilewski Jan
Published: September 2005

We have briefly reviewed the idea of studies aiming at such a bridging of the methodological gap between ab initio methods (or wave function theory (WFT)) and density functional theory (DFT) that would afford carrying over results concerning details of the structure of correlation effects from one method to the other. Special attention is paid to the problem of coverage of the WFT correlation effects by the exchange-correlation functionals of DFT. A short survey of the concept of supplementing energy-based investigations in this field by electron-density-based studies is given and illustrated by results for the Ne atom. DFT densities are generated for representatives of all four generations of presently used exchange-correlation functionals, including the recently developed orbital-dependent one. These densities are compared with WFT densities calculated at the MP2, MP3, and Brueckner determinant levels. It is found that the exchange-only parts of the local, gradient-corrected, and hybrid functionals account for the bulk of WFT correlation effects. The impact of the associated correlation functionals is very small and their physical nature is not quite clear. The situation is different for the orbital-dependent functional for which the exchange-only functional provides an almost exact description of the Hartree-Fock density. Here, the correlation effects are entirely represented by the correlation functional. Attention is also paid to the suitability of Kohn-Sham orbitals for the description of WFT correlation effects and to their presumptive similarity with Brueckner orbitals.
Just allocation and team loyalty: a new virtue ethic for emergency medicine
Authors: Girod J , Beckman A W
Published: September 2005

When traditional virtue ethics is applied to clinical medicine, it often claims as its goal the good of the individual patient, and focuses on the dyadic relationship between one physician and one patient. An alternative model of virtue ethics, more appropriate to the practice of emergency medicine, will be outlined by this paper. This alternative model is based on the assumption that the appropriate goal of the practice of emergency medicine is a team approach to the medical wellbeing of individual patients, constrained by the wellbeing of the patient population served by a particular emergency department. By defining boundaries and using the key virtues of justice and team loyalty, this model fits emergency practice well and gives care givers the conceptual clarity to apply this model to various conflicts both within the department and with those outside the department.
Individual and family consent to organ and tissue donation: is the current position coherent?
Authors: Wilkinson T M
Published: September 2005

The current position on the deceased’s consent and the family’s consent to organ and tissue donation from the dead is a double veto—each has the power to withhold and override the other’s desire to donate. This paper raises, and to some extent answers, questions about the coherence of the double veto. It can be coherently defended in two ways: if it has the best effects and if the deceased has only negative rights of veto. Whether the double veto has better effects than other policies requires empirical investigation, which is not undertaken here. As for rights, the paper shows that it is entirely possible that individuals have a negative right of veto but no positive right to compel acceptance of their offers. Thus if intensivists and transplant teams turn down the deceased’s offer, they do not thereby violate the deceased’s right. This leaves it open whether non-rights based reasons—such as avoiding bad publicity or distress —require intensivists and transplant teams to turn down or accept the deceased’s offer. This, however, is beyond the scope of this paper. The current position may or may not be wrong, but it is at least coherent.
What makes the best medical ethics journal? A North American perspective
Authors: Savulescu J , Viens A M
Published: September 2005

Background:There currently exist no data on the factors that contribute to determining why medical ethicists choose to review for and submit articles to medical ethics journals.

Objective:To establish which factors contribute to medical ethicists reviewing articles for or submitting them to medical ethics journals by consulting those who are active in this capacity.

Methods:Medical ethicists were surveyed to determine their incentives and disincentives for reviewing articles for or submitting them to medical ethics journals. Survey participants were chosen based on a review of the academic and research record of medical ethicists working in North America in higher education institutions.

Results:The most frequent incentives to reviewing journal articles were: an opportunity to contribute to the field/profession, the good reputation of the journal, the high impact factor of the journal, and to keep up to date on current research. The most frequent disincentives to reviewing journal articles were: time constraints due to academic commitments, the poor reputation of the journal, and time constraints caused by other editorial commitments (for example, reviewing for other journals/publishers). The most important incentives to submitting journal articles were: the good reputation of the journal, the quality of scholarship previously published in the journal, the impact factor of the journal, and a fast turn-around from acceptance to publication. The most important disincentives to submitting journal articles were: the poor reputation of the journal, the poor quality of work previously published in the journal, and a slow turn-around from acceptance to publication.

Conclusion:A series of factors that medical ethics journals should strive to employ to encourage reviewing and submission of articles are recommended.
The ethics of policy writing: how should hospitals deal with moral disagreement about controversial medical practices?
Authors: Winkler E C
Published: September 2005

Every healthcare organisation (HCO) enacts a multitude of policies, but there has been no discussion as to what procedural and substantive requirements a policy writing process should meet in order to achieve good outcomes and to possess sufficient authority for those who are asked to follow it.

Using, as an example, the controversy about patient’s refusal of blood transfusions, I argue that a hospital wide policy is preferable to individual decision making, because it ensures autonomy, quality, fairness, and efficiency.

Policy writing for morally controversial medical practices needs additional justification compared to policies on standard medical practices and secures legitimate authority for HCO members by meeting five requirements: all parties directed by the policy are represented; the deliberative process encompasses all of the HCO’s obligations; the rationales for the policy are made available; there is a mechanism for criticising, and for evaluating the policy.
On judgment and judgmentalism: how counselling can make people better
Authors: Gibson S
Published: September 2005

Counsellors, like other members of the caring professions, are required to practise within an ethical framework, at least in so far as they seek professional accreditation. As such, the counsellor is called upon to exercise her moral agency. In most professional contexts this requirement is, in itself, unproblematic. It has been suggested, however, that counselling practice does present a problem in this respect, in so far as the counsellor is expected to take a non-judgemental stance and an attitude of “unconditional positive regard” toward the client. If, as might appear to be the case, this stance and attitude are at odds with the making of moral judgments, the possibility of an adequate ethics of counselling is called into question. This paper explores the nature and extent of the problem suggesting that, understood in a Kantian context, non-judgmentalism can be seen to be at odds with neither the moral agency of the counsellor nor that of the client. Instead, it is argued, the relationship between the non-judgmental counsellor and her client is a fundamentally moral relationship, based on respect for the client’s unconditional worth as a moral agent.
Characteristics of selectors of nicotine replacement therapy
Authors: Shiffman S , Di Marino M E , Sweeney C T
Published: September 2005

Objective:To assess differences in demographic and smoking characteristics between smokers who have and have not used nicotine replacement therapy (NRT).

Design:Mail survey of US smokers from a national research panel.

Participants:Smokers 18 years and over who returned a survey on smoking (n  =  9630). The sample was weighted to match the US smoker population on age and sex.

Main outcome measures:Compared smokers who had/had not used NRT in a quit attempt (ever NRT use or over the counter (OTC) NRT use) on: demographic characteristics, nicotine dependence, history of craving and withdrawal, expected difficulty quitting, and self reported history of smoking related medical illness and psychopathology.

Results:NRT users (both ever-users and OTC users) were more likely to be older, male, and better educated. They were also heavier smokers, had experienced more craving and withdrawal upon quitting, and scored higher on measures of dependence. These differences were evident among light smokers, and remained even when smoking rate and time to first cigarette were controlled.

Conclusion:Smokers who elect to use NRT differ from non-NRT users in ways that predispose them to failure in cessation. Controlling for smoking rate and time to first cigarette does not eliminate these differences, even among light smokers. These differences must be considered when comparing the effectiveness of NRT among samples of smokers who self select their treatment and are likely to bias such outcome comparisons.
Tobacco industry influence on the definition of tobacco related disorders by the American Psychiatric Association: Table 1
Authors: Neuman M D , Bitton A , Glantz S A
Published: September 2005

Objective:TheDiagnostic and statistical manual of mental disorders, third edition (DSM-III), published by the American Psychiatric Association (APA) in 1980, included the first official definitions by the APA of tobacco dependence and tobacco withdrawal. Tobacco industry efforts to influence the DSM-III were investigated.

Method:Searches of previously secret tobacco industry documents, primarily the University of California San Francisco Legacy Tobacco Documents Library and British American Tobacco collections. Additional information was collected through discussions with editors of DSM-III, and library and general internet searches.

Results:The tobacco companies regarded the inclusion of tobacco dependence as a diagnosis in DSM-III as an adverse event. It worked to influence the content of the DSM-III and its impact following publication. These efforts included public statements and private lobbying of DSM-III editors and high ranking APA officers by prominent US psychiatrists with undisclosed ties to the tobacco industry. Following publication of DSM-III, tobacco companies contracted with two US professors of psychiatry to organise a conference and publish a monograph detailing controversies surrounding DSM-III.

Conclusions:The tobacco industry and its allies lobbied to narrow the definition of tobacco dependence in serial revisions of DSM-III. Following publication of DSM-III, the industry took steps to try to mitigate its impact. These actions mirror industry tactics to influence medical research and policy in various contexts worldwide. Such tactics slow the spread of a professional and public understanding of smoking and health that otherwise would reduce smoking, smoking induced disease, and tobacco company profits.
From strange bedfellows to natural allies: the shifting allegiance of fire service organisations in the push for federal fire-safe cigarette legislation: Table 1
Authors: Barbeau E M , Kelder G , Ahmed S , Mantuefel V , Balbach E D
Published: September 2005

Background:Cigarettes are the leading cause of fatal fires in the USA and are associated with one in four fire deaths. Although the technology needed to make fire-safe cigarettes has been available for many years, progress has been slow on legislative and regulatory fronts to require the tobacco industry to manufacture fire-safe cigarettes.

Method and results:We conducted a case study, drawing on data from tobacco industry documents, archives, and key informant interviews to investigate tobacco industry strategies for thwarting fire-safe cigarette legislation in the US Congress. We apply a theoretical framework that posits that policymaking is the product of three sets of forces: interests, institutions, and ideas, to examine tobacco industry behaviour, with a special focus on their and others’ attempts to court fire service organisations, including firefighters’ unions as allies. We discuss the implications of our findings for future policy efforts related to fire-safe cigarettes and other tobacco control issues.

Conclusions:Tobacco control advocates ought to: continue efforts to align key interest groups, including the firefighters unions; contest tobacco industry “diversionary” science tactics; and pursue a state based legislative strategy for fire-safe cigarettes, building towards national legislation.
Tobacco industry successfully prevented tobacco control legislation in Argentina
Authors: Sebrié E M , Barnoya J , Pérez-Stable E J , Glantz S A
Published: September 2005

Objective:To evaluate how transnational tobacco companies, working through their local affiliates, influenced tobacco control policymaking in Argentina between 1966 and 2005.

Methods:Analysis of internal tobacco industry documents, local newspapers and magazines, internet resources, bills from the Argentinean National Congress Library, and interviews with key individuals in Argentina.

Results:Transnational tobacco companies (Philip Morris International, British American Tobacco, Lorillard, and RJ Reynolds International) have been actively influencing public health policymaking in Argentina since the early 1970s. As in other countries, in 1977 the tobacco industry created a weak voluntary self regulating code to avoid strong legislated restrictions on advertising. In addition to direct lobbying by the tobacco companies, these efforts involved use of third party allies, public relations campaigns, and scientific and medical consultants. During the 1980s and 1990s efforts to pass comprehensive tobacco control legislation intensified, but the organised tobacco industry prevented its enactment. There has been no national activity to decrease exposure to secondhand smoke.

Conclusions:The tobacco industry, working through its local subsidiaries, has subverted meaningful tobacco control legislation in Argentina using the same strategies as in the USA and other countries. As a result, tobacco control in Argentina remains governed by a national law that is weak and restricted in its scope.
Tobacco industry consumer research on socially acceptable cigarettes
Authors: Ling P M , Glantz S A
Published: September 2005

Objective:To describe tobacco industry consumer research to inform the development of more “socially acceptable” cigarette products since the 1970s.

Methods:Analysis of previously secret tobacco industry documents.

Results:28 projects to develop more socially acceptable cigarettes were identified from Philip Morris, RJ Reynolds, British American Tobacco, and Lorillard tobacco companies. Consumer research and concept testing consistently demonstrated that many smokers feel strong social pressure not to smoke, and this pressure increased with exposure to smoking restrictions. Tobacco companies attempted to develop more socially acceptable cigarettes with less visible sidestream smoke or less odour. When presented in theory, these product concepts were very attractive to important segments of the smoking population. However, almost every product developed was unacceptable in actual product tests or test markets. Smokers reported the complete elimination of secondhand smoke was necessary to satisfy non-smokers. Smokers have also been generally unwilling to sacrifice their own smoking satisfaction for the benefit of others. Many smokers prefer smoke-free environments to cigarettes that produce less secondhand smoke.

Conclusions:Concerns about secondhand smoke and clean indoor air policies have a powerful effect on the social acceptability of smoking. Historically, the tobacco industry has been unable to counter these effects by developing more socially acceptable cigarettes. These data suggest that educating smokers about the health dangers of secondhand smoke and promoting clean indoor air policies has been difficult for the tobacco industry to counter with new products, and that every effort should be made to pursue these strategies.
Effect of the New York State cigarette fire safety standard on ignition propensity, smoke constituents, and the consumer market
Authors: Connolly G N , Alpert H R , Rees V , Carpenter C , Wayne G F , Vallone D , Koh H
Published: September 2005

Objectives:This study examines empirical evidence from the New York experience testing tobacco industry arguments made in opposition to fire safety standards for cigarettes.

Design:Percentages of cigarettes exhibiting full length burns (FLBs), cigarette sales before and following the implementation of the New York standards, a sample of retail cigarette prices, brand availability, and selected smoke constituent yields were compared between cigarettes sold in New York and two other states. Cigarette paper analysis was conducted on cigarettes sold in New York.

Results:New York cigarette brands averaged 10.0% FLBs as compared to 99.8% for California and Massachusetts brands. Reduced ignition propensity (RIP) appears to have been achieved by cigarette paper banding. Cigarette sales, prices, and brand availability do not appear to have been affected by the New York standards. Yields of the majority of smoke constituents tested did not differ substantially between RIP cigarettes sold in New York as compared to the same brands sold in Massachusetts. Average yields of tar, carbon monoxide, and two compounds were slightly higher, the yields of seven compounds were higher for one brand only, and nicotine was lower, among New York brands tested.

Conclusions:RIP cigarette brands have been designed to meet the New York fire safety standards. Their introduction has not affected cigarette sales or prices in New York. There is no evidence that the small increases in smoke constituent yields affect the already highly toxic nature of cigarette smoke. Data on smoking caused fires, deaths, and injuries dating from after the change in law are not yet available. Such data will be able to address the question of whether the demonstrated reduced ignition standards are associated with reduced fires and injuries. Based on the New York experience, prior industry objections to producing RIP cigarettes are unfounded. Other states and nations should adopt similar standards.
Health consequences of smoking 1–4 cigarettes per day
Authors: Bjartveit K , Tverdal A
Published: September 2005

Objectives:To determine the risk in men and women smoking 1–4 cigarettes per day of dying from specified smoking related diseases and from any cause.

Design:Prospective study.

Setting:Oslo city and three counties in Norway.

Participants:23 521 men and 19 201 women, aged 35–49 years, screened for cardiovascular disease risk factors in the mid 1970s and followed throughout 2002.

Outcomes:Absolute mortality and relative risks adjusted for confounding variables, of dying from ischaemic heart disease, all cancer, lung cancer, and from all causes.

Results:Adjusted relative risk (95% confidence interval) in smokers of 1–4 cigarettes per day, with never smokers as reference, of dying from ischaemic heart disease was 2.74 (2.07 to 3.61) in men and 2.94 (1.75 to 4.95) in women. The corresponding figures for all cancer were 1.08 (0.78 to 1.49) and 1.14 (0.84 to 1.55), for lung cancer 2.79 (0.94 to 8.28) and 5.03 (1.81 to 13.98), and for any cause 1.57 (1.33 to 1.85) and 1.47 (1.19 to 1.82).

Conclusions:In both sexes, smoking 1–4 cigarettes per day was associated with a significantly higher risk of dying from ischaemic heart disease and from all causes, and from lung cancer in women. Smoking control policymakers and health educators should emphasise more strongly that light smokers also endanger their health.
Bidi and cigarette smoking and risk of acute myocardial infarction among males in urban India
Authors: Rastogi T , Jha P , Reddy K S , Prabhakaran D , Spiegelman D , Stampfer M J , Willett W C , Ascherio A
Published: September 2005

Death from myocardial infarction (MI) in India is exacerbated by smoking of bidis or cigarettes. Smoking among 309 men with incident MI was compared to 618 age matched controls; 56% of the individuals with MI and 26% of controls were current smokers. Current smokers had a relative risk of 4.7 (95% confidence interval (CI) 3.2 to 6.9) compared to never smokers. Relative risks for smoking more than 10 cigarettes or 10 bidis daily were 9.1 (95% CI 4.7 to 17.7) and 8.1 (95% CI 4.3 to 15.3), respectively. It is estimated that smoking may cause 53% (95% CI 47% to 64%) of MIs among urban males in India.
Effect of local restaurant smoking regulations on progression to established smoking among youths
Authors: Siegel M , Albers A B , Cheng D M , Biener L , Rigotti N A
Published: September 2005

Background:While smoke-free restaurant laws are intended to protect the public from secondhand smoke exposure, they may also discourage smoking among adolescents. There is no evidence from longitudinal studies to test this hypothesis.

Objective:To examine the effect of local restaurant smoking regulations on progression to established smoking among adolescents.

Design, setting, and subjects:A cohort of 2623 Massachusetts youths, ages 12–17 years at baseline, was interviewed via random digit dial telephone survey in 2001–2002 and followed up two years later. A generalised estimating equations (GEE) logistic regression analysis was used and controlled for potential individual, household, and town level confounding factors.

Main outcome measure:Progression to established smoking during the two year follow up period (defined as having smoked 100 or more cigarettes in one’s life).

Results:Compared to youths living in towns with weak regulations, those living in towns with strong regulations (complete restaurant smoking bans) had less than half the odds of progression to established smoking (odds ratio (OR) 0.39, 95% confidence interval (CI) 0.24 to 0.66). The association was stronger for youths in towns with strong regulations in effect for two or more years (OR 0.11, 95% CI 0.03 to 0.37), although it was still present for those in towns with strong regulations in effect for less than two years (OR 0.55, 95% CI 0.33 to 0.90). No relationship was found between living in a town with a medium restaurant smoking regulation (restriction of smoking to enclosed, separately ventilated areas) and rates of progression to established smoking.

Conclusions:Local restaurant smoking bans may be an effective intervention to prevent youth smoking.
CO AS A CELLULAR SIGNALING MOLECULE
Authors: Kim Hong Pyo , Ryter Stefan W. , Choi Augustine M.K.
Published: September 2005

▪ Abstract  Many biological functions of heme oxygenase (HO), such as cytoprotection against oxidative stress, vasodilation, neurotransmission in the central or peripheral nervous systems, and anti-inflammatory, anti-apoptotic, or anti-proliferative potential, have been attributed to its enzymatic byproduct carbon monoxide (CO), although roles for biliverdin/bilirubin and iron have also been proposed. In addition to these well-characterized effects, recent findings reveal that HO-derived CO may act as an oxygen sensor and circadian modulator of heme biosynthesis. In lymphocytes, CO may participate in regulatory T cell function. A number of the known signaling effects of CO depend on stimulation of soluble guanylate cyclase and/or activation of mitogen-activated protein kinases (MAPK). Furthermore, modulation of caveolin-1 status may serve as an essential component of certain aspects of CO action, such as growth control. In this review, we summarize recent findings of the beneficial or detrimental effects of endogenous CO with an emphasis on the signaling pathways and downstream targets that trigger the action of this gas.
CHRONIC EFFECTS OF MECHANICAL FORCE ON AIRWAYS
Authors: Tschumperlin Daniel J. , Drazen Jeffrey M.
Published: September 2005

▪ Abstract  Airways are embedded in the mechanically dynamic environment of the lung. In utero, this mechanical environment is defined largely by fluid secretion into the developing airway lumen. Clinical, whole lung, and cellular studies demonstrate pivotal roles for mechanical distention in airway morphogenesis and cellular behavior during lung development. In the adult lung, the mechanical environment is defined by a dynamic balance of surface, tissue, and muscle forces. Diseases of the airways modulate both the mechanical stresses to which the airways are exposed as well as the structure and mechanical behavior of the airways. For instance, in asthma, activation of airway smooth muscle abruptly changes the airway size and stress state within the airway wall; asthma also results in profound remodeling of the airway wall. Data now demonstrate that airway epithelial cells, smooth muscle cells, and fibroblasts respond to their mechanical environment. A prominent role has been identified for the epithelium in transducing mechanical stresses, and in both the fetal and mature airways, epithelial cells interact with mesenchymal cells to coordinate remodeling of tissue architecture in response to the mechanical environment.
Interests, Relationships, Identities: Three Central Issues for Individuals and Groups in Negotiating Their Social Environment
Authors: Kelman Herbert C.
Published: September 2005

This chapter begins with a summary of a model, developed half a century ago, that distinguishes three qualitatively different processes of social influence: compliance, identification, and internalization. The model, originally geared to and experimentally tested in the context of persuasive communication, was subsequently applied to influence in the context of long-term relationships, including psychotherapy, international exchanges, and the socialization of national/ethnic identity. It has been extended to analysis of the relationship of individuals to social systems. Individuals' rule, role, and value orientations to a system—conceptually linked to compliance, identification, and internalization—predict different reactions to their own violations of societal standards, different patterns of personal involvement in the political system, and differences in attitude toward authorities and readiness to obey. In a further extension of the model, three approaches to peacemaking in international or intergroup conflicts are identified—conflict settlement, conflict resolution, and reconciliation—which, respectively, focus on the accommodation of interests, relationships, and identities, and are conducive to changes at the level of compliance, identification, and internalization.
SHAPING THE CONTEXT OF HEALTH: A Review of Environmental and Policy Approaches in the Prevention of Chronic Diseases
Authors: Brownson Ross C. , Haire-Joshu Debra , Luke Douglas A.
Published: September 2005

▪ Abstract  Given the growing attention on how environmental and policy interventions can affect chronic disease burden, our objectives are to describe (a) effective and promising interventions to address tobacco use, physical activity, and healthy eating and (b) lessons learned from the literature and practice experience in applying environmental and policy approaches. A total of 17 interventions were reviewed, organized across 3 domains affecting the physical environment/access, economic environment, and communication environment. Many of these interventions are effective. Several lessons are important to consider, such as the need to start with environmental and policy approaches, intervene comprehensively and across multiple levels, make use of economic evaluations, make better use of existing analytic tools, understand the politics and local context, address health disparities, and conduct sound policy research.
Levels of NAD+-dependent 15-hydroxyprostaglandin dehydrogenase are reduced in inflammatory bowel disease: evidence for involvement of TNF-α
Authors: Otani Taisuke , Yamaguchi Kentaro , Scherl Ellen , Du Baoheng , Tai Hsin-Hsiung , Greifer Melanie , Petrovic Lydia , Daikoku Takiko , Dey Sudhansu K. , Subbaramaiah Kotha , Dannenberg Andrew J.
Published: September 2005

Increased amounts of PGE2have been detected in the inflamed mucosa of patients with inflammatory bowel disease (IBD). This increase has been attributed to enhanced synthesis rather than reduced catabolism of PGE2. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) plays a major role in the catabolism of PGE2. In this study, we investigated whether amounts of 15-PGDH were altered in inflamed mucosa from patients with IBD. Amounts of 15-PGDH protein and mRNA were markedly reduced in inflamed mucosa from patients with Crohn's disease and ulcerative colitis. In situ hybridization demonstrated that 15-PGDH was expressed in normal colonic epithelium but was virtually absent in inflamed colonic mucosa from IBD patients. Because of the importance of TNF-α in IBD, we also determined the effects of TNF-α on the expression of 15-PGDH in vitro. Treatment with TNF-α suppressed the transcription of 15-PGDH in human colonocytes, resulting in reduced amounts of 15-PGDH mRNA and protein and enzyme activity. In contrast, TNF-α induced two enzymes (cyclooxygenase-2 and microsomal prostaglandin E synthase-1) that contribute to increased synthesis of PGE2. Overexpressing 15-PGDH blocked the increase in PGE2production mediated by TNF-α. Taken together, these results suggest that reduced expression of 15-PGDH contributes to the elevated levels of PGE2found in inflamed mucosa of IBD patients. The decrease in amounts of 15-PGDH in inflamed mucosa can be explained at least, in part, by TNF-α-mediated suppression of 15-PGDH transcription.
Activation of TGF-β1-TAK1-p38 MAPK pathway in spared cardiomyocytes is involved in left ventricular remodeling after myocardial infarction in rats
Authors: Matsumoto-Ida Madoka , Takimoto Yoshihito , Aoyama Takeshi , Akao Masaharu , Takeda Toshihiro , Kita Toru
Published: September 2005

Transforming growth factor-β1 (TGF-β1) alters myocardial gene expression, resulting in myocyte hypertrophy, through activation of TGF-β-activated kinase (TAK1), a member of the mitogen-activated protein kinase kinase kinase (MAPKKK) family. We hypothesized that the TGF-β1-TAK1-p38 MAPK pathway might be activated during ventricular remodeling after myocardial infarction (MI). One, 3, 7, and 14 days after ligation of the left anterior descending coronary artery, noninfarcted left ventricular tissue samples were obtained. Protein levels as well as mRNA levels of the signaling pathway, TGF-β1, TGF-β-receptors, and TAK1 increased in the noninfarcted myocardium in MI rats compared with sham-operated animals. Phosphorylation of MAPKK 3/6 (MKK3/6) and p38 MAPK, the downstream targets of TAK1, was also increased in the noninfarcted region. Moreover, an in vitro kinase assay revealed that the activated TAK1 in the noninfarcted myocardium was capable of activating recombinant MKK3/6, suggesting a causative role of TAK1 in the remodeling process. The activation of the TGF-β1-TAK1-p38 MAPK pathway paralleled the transcriptional upregulation of cardiac markers for ventricular hypertrophy, β-myosin heavy chain and atrial natriuretic peptide. TAK1 was mainly localized to cardiomyocytes, whereas TGF-β1 receptors were observed in vascular smooth muscle cells and fibroblasts as well as cardiomyocytes. Thus the TGF-β1-TAK1-MKK3/6-p38 MAPK pathway in the cardiomyocytes of noninfarcted spared myocardium is activated after acute MI and may play an important role in ventricular hypertrophy and post-MI remodeling in rats.
Differential effects of aging on limb blood flow in humans
Authors: Donato Anthony J. , Uberoi Abhimanyu , Wray D. Walter , Nishiyama Steven , Lawrenson Lesley , Richardson Russell S.
Published: September 2005

Aging appears to attenuate leg blood flow during exercise; in contrast, such data are scant and do not support this contention in the arm. Therefore, to determine whether aging has differing effects on blood flow in the arm and leg, eight young (22 ± 6 yr) and six old (71 ± 15 yr) subjects separately performed dynamic knee extensor [0, 3, 6, 9 W; 20, 40, 60% maximal work rate (WRmax)] and handgrip exercise (3, 6, 9 kg at 0.5 Hz; 20, 40, 60% WRmax). Arterial diameter, blood velocity (Doppler ultrasound), and arterial blood pressure (radial tonometry) were measured simultaneously at each of the submaximal workloads. Quadriceps muscle mass was smaller in the old (1.6 ± 0.1 kg) than the young (2.1 ± 0.2 kg). When normalized for this difference in muscle mass, resting seated blood flow was similar in young and old subjects (young, 115 ± 28; old, 114 ± 39 ml·kg−1·min−1). During exercise, blood flow and vascular conductance were attenuated in the old whether expressed in absolute terms for a given absolute workload or more appropriately expressed as blood flow per unit muscle mass at a given relative exercise intensity (young, 1,523 ± 329; old, 1,340 ± 157 ml·kg−1·min−1 at 40% WRmax). In contrast, aging did not affect forearm muscle mass or attenuate rest or exercise blood flow or vascular conductance in the arm. In conclusion, aging induces limb-specific alterations in exercise blood flow regulation. These alterations result in reductions in leg blood flow during exercise but do not impact forearm blood flow.
Protective effect of gap junction uncouplers given during hypoxia against reoxygenation injury in isolated rat hearts
Authors: Rodríguez-Sinovas Antonio , García-Dorado David , Ruiz-Meana Marisol , Soler-Soler Jordi
Published: September 2005

It has been shown that cell-to-cell chemical coupling may persist during severe myocardial hypoxia or ischemia. We aimed to analyze the effects of different, chemically unrelated gap junction uncouplers on the progression of ischemic injury in hypoxic myocardium. First, we analyzed the effects of heptanol, 18α-glycyrrhetinic acid, and palmitoleic acid on intracellular Ca2+ concentration during simulated hypoxia (2 mM NaCN) in isolated cardiomyocytes. Next, we analyzed their effects on developed and diastolic tension and electrical impedance in 47 isolated rat hearts submitted to 40 min of hypoxia and reoxygenation. All treatments were applied only during the hypoxic period. Cell injury was determined by lactate dehydrogenase (LDH) release. Heptanol, but not 18α-glycyrrhetinic acid nor palmitoleic acid, attenuated the increase in cytosolic Ca2+ concentration induced by simulated ischemia in cardiomyocytes and delayed rigor development (rigor onset at 7.31 ± 0.71 min in controls vs. 14.76 ± 1.44 in heptanol-treated hearts, P < 0.001) and the onset of the marked changes in electrical impedance (tissue resistivity: 4.02 ± 0.29 vs. 7.75 ± 1.84 min, P = 0.016) in hypoxic rat hearts. LDH release from hypoxic hearts was minimal and was not significantly modified by drugs. However, all gap junction uncouplers, given during hypoxia, attenuated LDH release during subsequent reoxygenation. Dose-response analysis showed that increasing heptanol concentration beyond the level associated with maximal effects on cell coupling resulted in further protection against hypoxic injury. In conclusion, gap junction uncoupling during hypoxia has a protective effect on cell death occurring upon subsequent reoxygenation, and heptanol has, in addition, a marked protective effect independent of its uncoupling actions.
Mechanism of osmotic flow in a periodic fiber array
Authors: Zhang Xiaobing , Curry Fitz-Roy , Weinbaum Sheldon
Published: September 2005

The classic analysis by Anderson and Malone ( Biophys J 14: 957–982, 1974) of the osmotic flow across membranes with long circular cylindrical pores is extended to a fiber matrix layer wherein the confining boundaries are the fibers themselves. The equivalent of the well-known result for the reflection coefficient σ0= (1 − φ)2, where φ is the partition coefficient, is derived for a periodic fiber array of hexagonally ordered core proteins. The boundary value problem for the potential energy function describing the solute distribution surrounding each fiber is solved by defining an equivalent fluid annulus in which the pressures and osmotic forces are determined. This model is of special interest in the osmotic flow of water across a capillary wall, where recent experimental studies suggest that the endothelial glycocalyx is a quasiperiodic fiber array that serves as the primary molecular sieve for plasma proteins. Results for the reflection coefficient are presented in terms of two dimensionless numbers, α = a/ R and β = b/ R, where a and b are the solute and fiber radii, respectively, and R is the outer radius of the fluid annulus. In general, the results differ substantially from the classic expression for a circular pore because of the large difference in the shape of the boundary along which the osmotic force is generated. However, as in circular pore theory, one finds that the reflection coefficients for osmosis and filtration are the same.
Dilatory responses to estrogenic compounds in small femoral arteries of male and female estrogen receptor-β knockout mice
Authors: Cruz Maria Natalia , Douglas Gillian , Gustafsson Jan-Å , Poston Lucilla , Kublickiene Karolina
Published: September 2005

The objectives of this study were to determine whether acute dilatory responses to estrogen receptor agonists are altered in isolated arteries from estrogen receptor β-deficient mice (β-ERKO) and to gain insight into the role of nitric oxide (NO) in these responses. Femoral arteries (∼250 μm) from male and female β-ERKO mice and wild-type (WT) littermates (26 female, 13 in each group; and 24 male, 12 in each group) were mounted on a Multi-Myograph. Concentration-response curves to 17β-estradiol (17β-E2) and the selective estrogen receptor-α (ER-α) agonist propyl-[1H]-pyrazole-1,3,5-triy-trisphenol (PPT) were obtained before and after NO synthase (NOS) inhibition [ Nω-nitro-l-arginine methyl ester (l-NAME), 0.1 mM] in arteries preconstricted with U-46619 (a thromboxane analog). In WT mice, responses to the potent estrogen receptor-β (ER-β) agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN) and the contribution of NO were also assessed. Concentration-response curves to 17β-E2and PPT were similar in arteries from WT and β-ERKO mice of both genders, but NO-mediated relaxation was different, since l-NAME reduced 17β-E2mediated relaxation in arteries from male and female β-ERKO but not WT mice ( P < 0.05). NOS inhibition reduced dilation to PPT in arteries from male and female WT mice, as well as arteries from female β-ERKO mice ( P < 0.05). Responses to DPN in arteries from WT female and male mice did not differ after NOS inhibition. The acute dilatory responses to estrogenic compounds are similar in WT and β-ERKO mice but differ mechanistically. Because NO appeared to contribute to responses to 17β-E2in arteries from β-ERKO but not WT mice, the presence of ER-β apparently inhibits ER-α-mediated NO relaxation.