bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alternative stabilities of a proline‐rich antibacterial peptide in vitro and in vivo
Authors: Noto Paul Bart , Abbadessa Giovanni , Cassone Marco , Mateo George D. , Agelan Alexis , Wade John D. , Szabo Dora , Kocsis Bela , Nagy Karoly , Rozgonyi Ferenc , Otvos Laszlo 
Published: April 2008

AbstractThe proline‐rich designer antibacterial peptide dimer A3‐APO is currently under preclinical development for the treatment of systemic infections caused by antibiotic‐resistant Gram‐negative bacteria. The peptide showed remarkable stability in 25% mouse serum in vitro, exhibiting a half‐life of ∼100 min as documented by reversed‐phase chromatography. Indeed, after a 30‐min incubation period in undiluted mouse serum ex vivo, mass spectrometry failed to identify any degradation product. The peptide was still a major peak in full blood ex vivo, however, with degradation products present corresponding to amino‐terminal cleavage. When injected into mice intravenously, very little, if any unmodified peptide could be detected after 30 min. Nevertheless, the major early metabolite, a full single‐chain fragment, was detectable until 90 min, and this fragment exhibited equal or slightly better activity in the broth microdilution antimicrobial assay against a panel of resistant Enterobactericeae strains. The Chex1‐Arg20 metabolite, when administered three times at 20 mg/kg to mice infected with a sublethal dose (over LD50) of an extended spectrum β‐lactamase‐producing Escherichia coli strain, completely sterilized the mouse blood, similar to imipenem added at a higher dose. The longer and presumably more immunogenic prodrug A3‐APO, injected subcutaneously twice over a 3‐wk period, did not induce any antibody production, indicating the suitability of this peptide or its active metabolite for clinical development.
High LET radiation enhances apoptosis in mutated p53 cancer cells through Caspase‐9 activation
Authors: Yamakawa Nobuhiro , Takahashi Akihisa , Mori Eiichiro , Imai Yuichiro , Furusawa Yoshiya , Ohnishi Ken , Kirita Tadaaki , Ohnishi Takeo 
Published: April 2008

Although mutations in the p53 gene can lead to resistance to radiotherapy, chemotherapy and thermotherapy, high linear energy transfer (LET) radiation induces apoptosis regardless of p53 gene status in cancer cells. The aim of this study was to clarify the mechanisms involved in high LET radiation‐induced apoptosis. Human gingival cancer cells (Ca9‐22 cells) containing a mutated p53 (mp53) gene were irradiated with X‐rays, C‐ion (13–100 KeV/µm), or Fe‐ion beams (200 KeV/µm). Cellular sensitivities were determined using colony forming assays. Apoptosis was detected and quantified with Hoechst 33342 staining. The activity of Caspase‐3 was analyzed with Western blotting and flow cytometry. Cells irradiated with high LET radiation showed a high sensitivity with a high frequency of apoptosis induction. The relative biological effectiveness (RBE) values for the surviving fraction and apoptosis induction increased in a LET‐dependent manner. Both RBE curves reached a peak at 100 KeV/µm, and then decreased at values over 100 KeV/µm. When cells were irradiated with high LET radiation, Caspase‐3 was cleaved and activated, leading to poly (ADP‐ribose) polymerase (PARP) cleavage. In addition, Caspase‐9 inhibitor suppressed Caspase‐3 activation and apoptosis induction resulting from high LET radiation to a greater extent than Caspase‐8 inhibitor. These results suggest that high LET radiation enhances apoptosis by activation of Caspase‐3 through Caspase‐9, even in the presence of mp53. (Cancer Sci 2008; 99: 1455–1460)
Distinguishing signs of opioid overdose and indication for naloxone: an evaluation of six overdose training and naloxone distribution programs in the United States
Authors: Green Traci C. , Heimer Robert , Grau Lauretta E. 
Published: April 2008

ABSTRACTAims  This study assessed overdose and naloxone administration knowledge among current or former opioid abusers trained and untrained in overdose–response in the United States.Design and participants  Ten individuals, divided equally between those trained or not trained in overdose recognition and response, were recruited from each of six sites (n = 62).Setting  US‐based overdose training and naloxone distribution programs in Baltimore, San Francisco, Chicago, New York and New Mexico.Measurements  Participants completed a brief questionnaire on overdose knowledge that included the task of rating 16 putative overdose scenarios for: (i) whether an overdose was occurring and (ii) if naloxone was indicated. Bivariate and multivariable analyses compared results for those trained to untrained. Responses were also compared to those of 11 medical experts using weighted and unweighted kappa statistics.Findings  Respondents were primarily male (72.6%); 45.8% had experienced an overdose and 72% had ever witnessed an overdose. Trained participants recognized more opioid overdose scenarios accurately (t60 = 3.76, P < 0.001) and instances where naloxone was indicated (t59 = 2.2, P < 0.05) than did untrained participants. Receipt of training and higher perceived competency in recognizing signs of an opioid overdose were associated independently with higher overdose recognition scores. Trained respondents were as skilled as medical experts in recognizing opioid overdose situations (weighted kappa = 0.85) and when naloxone was indicated (kappa = 1.0).Conclusions  Results suggest that naloxone training programs in the United States improve participants' ability to recognize and respond to opioid overdoses in the community. Drug users with overdose training and confidence in their abilities to respond may effectively prevent overdose mortality.
Women's gender role orientation predicts their drinking patterns: a follow‐up study of Czech women
Authors: Kubička Luděk , Csémy Ladislav 
Published: April 2008

ABSTRACTAims  Evaluation of the hypothesis that women's non‐traditional gender role orientation contributes to drinking patterns typical for men.Design  A two‐wave prospective study with data collected in 1992 and 1997.Setting  The data reflect Czech women's changing gender role orientation and their drinking patterns during a historical period of post‐totalitarian societal transformation.Participants  A representative cohort of 497 Prague women aged 30–59 years in 1997.Measurements  Face‐to‐face interview data on drinking patterns and individually collected original questionnaire on gender role orientation.Findings  An analysis of the principal components of the gender role orientation questionnaire has led to four components, designated as egalitarianism, liberalism, feminism and hedonism. Constructed role orientation scales had Cronbachs's α reliabilities ranging from 0.57 to 0.74. With possible confounders controlled (thanks mainly to the prospective design), non‐traditional gender role orientation components assessed in 1992 predicted the usual quantities of alcohol women have consumed per occasion in 1997, as well as three hazardous drinking patterns (occasional use of ≥ 96 g alcohol, usual use of ≥ 48 g and daily intake of ≥ 40 g). Specifically, women's usual quantity per occasion and occasional use of ≥ 96 g were predicted by egalitarianism and hedonism, and hedonism predicted usual use of ≥ 48 g as well as average daily intake of ≥ 40 g ethanol.Conclusions  Women's gender role orientation can be associated with their drinking patterns with non‐traditional gender role identification being associated with greater likelihood of hazardous drinking.
Genetic approaches to addiction: genes and alcohol
Authors: Ducci Francesca , Goldman David 
Published: April 2008

ABSTRACTAims  Alcoholism is a chronic relapsing disorder with an enormous societal impact. Understanding the genetic basis of alcoholism is crucial to characterize individuals' risk and to develop efficacious prevention and treatment strategies.Methods  We examined the available scientific literature to provide an overview of different approaches that are being integrated increasingly to advance our knowledge of the genetic bases of alcoholism. Examples of genes that have been shown to influence vulnerability to alcoholism and related phenotypes are also discussed.Results  Genetic factors account for more than 50% of the variance in alcoholism liability. Susceptibility loci for alcoholism include both alcohol‐specific genes acting either at the pharmacokinetic or pharmacodynamic levels, as well as loci moderating neuronal pathways such as reward, behavioral control and stress resiliency, that are involved in several psychiatric diseases. In recent years, major progress in gene identification has occurred using intermediate phenotypes such as task‐related brain activation that confer the advantage of increased power and the opportunity of exploring the neuronal mechanisms through which genetic variation is translated into behavior. Fundamental to the detection of gene effects is also the understanding of the interplay between genes as well as genes/environment interactions. Whole Genome Association studies represent a unique opportunity to identify alcohol‐related loci in hypothesis‐free fashion. Finally, genome‐wide analyses of transcripts and chromatin remodeling promise an increase in our understanding of the genome function and of the mechanisms through which gene and environment cause diseases.Conclusions  Although the genetic bases of alcoholism remain largely unknown, there are reasons to think that more genes will be discovered in the future. Multiple and complementary approaches will be required to piece together the mosaic of causation.
The effect of proactively identifying smokers and offering smoking cessation support in primary care populations: a cluster‐randomized trial
Authors: Murray Rachael L. , Coleman Timothy , Antoniak Marilyn , Stocks Joanne , Fergus Alexia , Britton John , Lewis Sarah A. 
Published: April 2008

ABSTRACTAims  To establish whether proactively identifying all smokers in primary care populations and offering smoking cessation support is effective in increasing long‐term abstinence from smoking.Design  Cluster randomized controlled trial.Setting  Twenty‐four general practices in Nottinghamshire, randomized by practice to active or control intervention.Participants  All adult patients registered with the practices who returned a questionnaire confirming that they were current smokers (n = 6856).Intervention  Participants were offered smoking cessation support by letter and those interested in receiving it were contacted and referred into National Health Service (NHS) stop smoking services if required.Measurements  Validated abstinence from smoking, use of smoking cessation services and number of quit attempts in continuing smokers at 6 months.Findings  Smokers in the intervention group were more likely than controls to report that they had used local cessation services during the study period [16.6% and 8.9%, respectively, adjusted odds ratio (OR) 2.09, 95% confidence interval (CI) 1.57–2.78], and continuing smokers (in the intervention group) were more likely to have made a quit attempt in the last 6 months (37.4% and 33.3%, respectively, adjusted OR 1.23, 95% CI 1.01–1.51). Validated point prevalence abstinence from smoking at 6 months was higher in the intervention than the control groups (3.5% and 2.5%, respectively) but the difference was not statistically significant (adjusted OR controlling for covariates: 1.64, 95% CI 0.92–2.89).Conclusions  Proactively identifying smokers who want to quit in primary care populations, and referring them to a cessation service, increased contacts with cessation services and the number of quit attempts. We were unable to detect a significant effect on long‐term cessation rates, but the study was not powered to detect the kind of difference that might be expected.
Methamphetamine suppression and route of administration: precursor regulation impacts on snorting, smoking, swallowing and injecting
Authors: Cunningham James K. , Liu Lon‐Mu , Muramoto Myra 
Published: April 2008

ABSTRACTAims  The route of drug administration affects risk for dependence and medical harm. This study examines whether routes used by methamphetamine treatment participants were impacted by a major drug suppression policy—federal regulation of the methamphetamine precursor chemicals ephedrine and pseudoephedrine.Design  Autoregressive‐integrated moving average (ARIMA) intervention time–series analysis.Setting  California (1992–2004).Interventions  Ephedrine single‐ingredient products regulation, implemented August 1995; ephedrine with other active medicinal ingredients regulation, implemented October 1996; pseudoephedrine products regulation, implemented October 1997.Measurements  Monthly counts of non‐coerced methamphetamine treatment admissions reporting snorting, smoking, swallowing or injecting.Findings  After rising sharply, snorting, smoking, swallowing and injecting admissions dropped 50%, 43%, 26% and 26%, respectively, when the 1995 regulation was implemented. Snorting also dropped 38% at the time of the 1997 regulation. Snorting, swallowing and injecting remained at lower levels to the end of the study period. Smoking resurged (40%) at the time of the 1996 regulation and continued rising.Conclusions  Precursor regulation was associated with changes in the administration of methamphetamine. Injecting, the route with the greatest health risk, entered a long‐term reduction. So, too, did snorting and swallowing, two routes with lower risk for dependence. In contrast, smoking, which has a relatively high risk for dependence, dropped, then rebounded and entered a long‐term rise. A possible explanation is that injecting, snorting and swallowing were largely linked with US domestic methamphetamine production, which has yet to recover from the regulations. While Mexican production, which was impacted only temporarily by the regulations and has supplanted domestic production, may have helped to diffuse smoking, a route with which it is historically correlated.
Erythrocyte vesiculation: a self‐protective mechanism?
Authors: Willekens Frans L. A. , Werre Jan M. , Groenen‐Döpp Yvonne A. M. , Roerdinkholder‐Stoelwinder Bregt , De Pauw Ben , Bosman Giel J. C. G. M. 
Published: April 2008

SummaryPrevious studies demonstrated that 20% of haemoglobin is lost from circulating erythrocytes during their total lifespan by vesiculation. To study whether removal molecules other than membrane‐bound haemoglobin were present in erythrocyte‐derived vesicles, flow cytometry and immunoblot analysis were employed to examine the presence of phosphatidylserine (PS) and IgG, and senescent cell antigens respectively. It was demonstrated that 67% of glycophorin A‐positive vesicles exposed PS, and that half of these vesicles also contained IgG. Immunoblot analysis revealed the presence of a breakdown product of band 3 that reacted with antibodies directed against senescent erythrocyte antigen‐associated band 3 sequences. In contrast, only the oldest erythrocytes contained senescent cell antigens and IgG, and only 0·1% of erythrocytes, of all ages, exposed PS. It was concluded that vesiculation constitutes a mechanism for the removal of erythrocyte membrane patches containing removal molecules, thereby postponing the untimely elimination of otherwise healthy erythrocytes. Consequently, these same removal molecules mediate the rapid removal of erythrocyte‐derived vesicles from the circulation.
Rapid and sustained clearance of circulating lymphoma cells after chemotherapy plus rituximab: clinical significance of quantitative t(14;18) PCR monitoring in advanced stage follicular lymphoma patients†
Authors: Hirt Carsten , Schüler Frank , Kiefer Thomas , Schwenke Cornelia , Haas Antje , Niederwieser Dietger , Neser Sabine , Aßmann Michael , Srock Stefanie , Rohrberg Robert , Dachselt Klaus , Leithäuser Malte , Rabkin Charles S. , Herold Michael , Dölken Gottfried 
Published: April 2008

SummaryThis study of first‐line treatment in advanced‐stage follicular lymphoma patients analysed the effects of MCP (mitoxantrone, chlorambucil and prednisolone) chemotherapy alone or in combination with rituximab (R‐MCP) on circulating lymphoma cells (CLC) and assessed the prognostic value of a quantitative monitoring of CLC. CLC numbers were determined by quantitative polymerase chain reaction (PCR) for the t(14;18)‐translocation or by allele‐specific PCR for rearranged immunoglobulin heavy chain genes. We analysed blood samples from 43 patients treated in a randomized trial comparing eight cycles of MCP versus R‐MCP. Clearance of CLC at the end of therapy was achieved in 21/25 patients (84%) treated with R‐MCP compared with 0/18 after MCP alone (P < 0·0001). A ≥2 log CLC reduction was associated with a favourable clinical response (P = 0·0004) and prolonged event‐free survival (P = 0·02). In R‐MCP patients, stable CLC numbers or consistently PCR‐negative blood samples were associated with a continuing clinical remission whereas in two patients a relapse was preceded by a ≥2 log CLC increase. This study demonstrated that R‐MCP led to a rapid and sustained eradication of CLC and a ≥2 log CLC reduction was associated with a superior quality and duration of the clinical response.
Ovalbumin‐sensitized mice are good models for airway hyperresponsiveness but not acute physiological responses to allergen inhalation
Authors: Zosky G. R. , Larcombe A. N. , White O. J. , Burchell J. T. , Janosi T. Z. , Hantos Z. , Holt P. G. , Sly P. D. , Turner D. J. 
Published: April 2008

SummaryBackground
Asthma is a chronic inflammatory disease that is characterized clinically by airway hyperresponsiveness (AHR) to bronchoconstricting agents. The physiological response of the asthmatic lung to inhaled allergen is often characterized by two distinct phases: an early‐phase response (EPR) within the first hour following exposure that subsides and a late‐phase response (LPR) that is more prolonged and may occur several hours later. Mouse models of asthma have become increasingly popular and should be designed to exhibit an EPR, LPR and AHR.Objective
To determine whether a common model of asthma is capable of demonstrating an EPR, LPR and AHR.Methods
BALB/c mice were sensitized to ovalbumin (OVA) and challenged with one or three OVA aerosols. Changes in lung mechanics in response to allergen inhalation were assessed using a modification of the low‐frequency forced oscillation technique (LFOT). In order to assess AHR, changes in lung mechanics in response to aerosolized methacholine were assessed using LFOT. Inflammatory cell infiltration into the lung was measured via bronchoalveolar lavage (BAL). ELISAs were used to measure inflammatory cytokines in the BAL and levels of IgE in the serum.Results
An EPR was only detectable after three OVA aerosols in approximately half of the mice studied. There was no evidence of an LPR despite a clear increase in cellular infiltration 6 h post‐allergen challenge. AHR was present after a single OVA aerosol but not after three OVA aerosols.Conclusions
The lack of an LPR, limited EPR and the absence of a link between the LPR and AHR highlight the limitations of this mouse model as a complete model of the lung dysfunction associated with asthma.
Anti tumour necrosis‐α therapy increases the number of FOXP3+ regulatory T cells in children affected by Crohn’s disease
Authors: Ricciardelli Ida , Lindley Keith J. , Londei Marco , Quaratino Sonia 
Published: April 2008

SummaryCrohn’s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. Its pathogenesis is not completely understood, though the prevailing model is that the intestinal flora drives a strong intestinal T helper 1 (Th1)/Th17 type immune response and inflammation in the genetically susceptible host. This leads to overly aggressive T‐cell responses to normal bacteria causing tissue damage. Intestinal homeostasis and maintenance of tolerance to harmless antigens in the intestine has been shown to be maintained by CD4+ CD25+ T regulatory cells (Treg) in animal models of inflammatory bowel diseases. Here we investigated whether Infliximab, a chimeric monoclonal antibody directed against tumour necrosis factor (TNF)‐α shown to be highly effective in the treatment of CD, has any effect on mucosal CD4+ CD25+ (FOXP3+) Tregs. Colonic mucosal biopsies from children with active Crohn’s disease treated in vivo with Infliximab and controls were analysed to determine FOXP3 expression by immunofluorescence and reverse transcription–polymerase chain reaction. We observed that FOXP3+ T cells were significantly reduced in mucosa of CD patients with active disease compared with controls and restored to normal following Infliximab treatment. The frequency of FOXP3+ cells and mRNA expression was significantly increased in CD mucosa from patients treated in vivo with Infliximab compared with CD patients treated with conventional therapies. In conclusion, we show that Infliximab treatment does not solely neutralize soluble TNF‐α, but also affects activation and possibly expansion of mucosal regulatory T cells. We suggest that anti TNF‐α immunotherapy can also restore mucosal homeostasis in Crohn’s disease.
The adoption behaviour of information technology industry in increasing business‐to‐business integration sophistication
Authors: Wang William Y C , Heng Michael S H , Chau Patrick Y K 
Published: April 2008

AbstractA supply chain is not a linear type of inter‐firm structure but is often considered as a network. Business networks are underpinned by the firms' resources, social legitimacy and associated power, which are also seen in the adoption theories of business‐to‐business integration (B2Bi) in the supply chain. However, there appears to be scarcity of the discussion on the theoretical relationship between them. This paper aims to enrich the previous findings of technology adoption theories in a business‐to‐business context by proposing a structural model and using Structural Equation Modelling approach to test it. It focuses on the integrated supply chain to test, analyse and extend the adoption factors to the use of computer‐based information systems (IS). The survey data were collected in the Taiwanese Information Technology Industry. The path analyses indicate the answers for three issues raised from the research framework and confirm the associations between a firm's existing system support readiness and the network determinants outside organizational boundaries. Further, it identifies the interrelationships among these factors and indicates that some of them mediate the enterprises' behaviour on investments to increase current IS for B2Bi purposes.
Preservation and shelf‐life extension of shrimps and clams by high hydrostatic pressure
Authors: Büyükcan Mehmet , Bozoglu Faruk , Alpas Hami 
Published: April 2008

SummaryClam (Venus gallina) and shrimp (Parapenaeus longirostris) samples were high hydrostatic pressure (HHP) treated at 200, 220 and 250 MPa at 25, 30, 40 and 50 °C for 10 and 20 min. Based on the results of microbial reduction, the best combinations of HHP treatments were determined as 250 MPa, 50 °C, 10 min for shrimps and 220 MPa, 50 °C, 10 min for clams. HHP‐treated samples stored at 25 °C (room tempertur) and 4 °C (refrigeration temperature) were analysed. According to the results evaluated, shelf‐life of shrimps was found to be 12 and 16 days for storage at room and refrigeration temperatures, respectively, as compared with 4 days for non‐HHP‐treated samples at 4 °C. Similarly shelf‐life for the clam samples was found to be 12 days for storage at room temperature and 18 days for storage at refrigeration temperature as compared with 4 days for non‐HHP‐treated samples at 4 °C.