bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of multiple primary cancers in Nagasaki atomic bomb survivors: Association with radiation exposure
Authors: Nakashima Masahiro , Kondo Hisayoshi , Miura Shiro , Soda Midori , Hayashi Tomayoshi , Matsuo Takeshi , Yamashita Shunichi , Sekine Ichiro 
Published: November 2007

To assess the effects of atomic bomb radiation on the incidence of multiple primary cancers (MPC), we analyzed the association between the incidence of second primary cancers in survivors of the atomic bombing of Nagasaki, and exposure distance. The incidence rate (IR) of a second primary cancer was calculated and stratified by the distance from the hypocenter and age at the time of bombing for the years 1968 through 1999. The IR of the first primary cancer was also calculated and compared with the second primary cancer to determine whether atomic bomb radiation was associated with the multiplicity of tumors. There were 511 confirmed cases of MPC in the 7572 cancer‐bearing survivors. The crude IR was 27.6 per 100 000 person‐years. The IR of second primaries decreased significantly with increasing distance from the hypocenter: relative risk, 0.89 per 1.0 km; 95% confidence interval, 0.84–0.94. A significant decrease was also noted for those of older ages at the time of the bombing, based on the attained age of the second primary cancer: relative risk, 0.91 per 1 year; 95% confidence interval, 0.90–0.92. These findings suggest that the radiation has affected the incidence of MPC. Furthermore, when compared with the first primary cancer, a stronger distance effect was suggested on the occurrence of a second primary cancer in the survivors. The present study suggests the significance of atomic bomb radiation on MPC in the survivors. These results on the incidence of MPC in the tumor‐bearing survivors and its correlations with the atomic bombing of 62 years ago are described for the first time in this report. (Cancer Sci 2008; 99: 87–92)
Oral challenges are needed in the diagnosis of β‐lactam hypersensitivity
Authors: Bousquet P. J. , Pipet A. , Bousquet‐Rouanet L. , Demoly P. 
Published: November 2007

SummaryBackgroundβ‐lactams continue to remain the most commonly involved drug family in allergic drug reactions. They are often essential and there is a cost‐effective and favourable risk‐benefit ratio for the exploration of all suspicions of β‐lactam allergy. A firm diagnosis is always based on skin tests and sometimes on provocation tests. Recommendations have been published by allergy societies and distinguished scientists but they are not always concordant and can lead to some confusion for the practicing allergologist. The situation has even worsened since the world wide withdrawal of these penicillin determinants and since the predominance of amoxicillin and cephalosporin prescriptions in most countries.Objective – MethodIn a recent article, it was stated that patients with a penicillin allergy history and negative skin tests to major and minor penicillin determinants are at a low risk of relapse (0–5%) when receiving a β‐lactam. In this paper, our Drug Allergy and Hypersensitivity Database, a cohort database, was used to demonstrate that this statement is false. Standardized European Network for Drug Allergy questionnaires, skin test and challenge procedures were followed.ResultsOne‐thousand two‐hundred and eighteen subjects, 69.8% of female, 51.7% of atopics, were included. 21.1% had a true β‐lactam allergy confirmed by skin tests (178, 69.3%) or by drug provocation (79, 30.7%). 17.4% of the patients with negative skin tests to major and minor penicillin determinants were positive for a β‐lactam.ConclusionIn the diagnosis of β‐lactams allergy, if all skin tests are negative, skin tests with other determinants and provocation tests under strict surveillance are mandatory.
Leisure time but not occupational physical activity significantly affects cardiovascular risk factors in an adult population
Authors: Sofi F. , Capalbo A. , Marcucci R. , Gori A. M. , Fedi S. , Macchi C. , Casini A. , Surrenti C. , Abbate R. , Gensini G. F. 
Published: November 2007

AbstractBackground  A large number of studies have demonstrated that regular physical activity during leisure time (LTPA) accounts for a significant protection against cardiovascular diseases (CVD). On the other hand, conflicting findings on the beneficial effects of occupational physical activity (OPA) have been reported. The aim of this study is to evaluate the possible influence of different amounts of LTPA and OPA on circulating levels of several parameters associated with an increased risk of CVD.Materials and methods  We studied 932 individuals (365 M; 567 F, with a mean age of 54 years) living in Florence, Italy, who were enrolled in a population study conducted between 2002 and 2004. Subjects were divided into three classes of LTPA and OPA according to a score derived from a questionnaire that assessed the amount of physical activity performed.Results  LTPA was inversely related to body mass index (BMI), hip circumference, diastolic blood pressure and triglycerides, as well as directly correlated with high‐density lipoprotein (HDL) cholesterol. Likewise, a higher OPA was found to be associated with higher HDL cholesterol levels. Moreover, a multivariate logistical regression analysis, adjusted for possible confounders, showed that a moderate‐to‐high intensity of LTPA was able to confer a significant protection against having abnormal levels of BMI, waist circumference and triglycerides, main features of the metabolic syndrome, whereas no associations between these parameters and OPA were observed.Conclusions  A moderate‐to‐high LTPA was found to be significantly associated with a more favourable cardiovascular risk profile in terms of anthropometric, metabolic and lipid parameters among an Italian population. In addition, a relationship between OPA and HDL‐cholesterol was reported.
Immunological decision‐making: how does the immune system decide to mount a helper T‐cell response?
Authors: Kaiko Gerard E. , Horvat Jay C. , Beagley Kenneth W. , Hansbro Philip M. 
Published: November 2007

SummaryAberrant T‐cell responses underpin a range of diseases, including asthma and allergy and autoimmune diseases. Pivotal immune elements of these diseases are the development of antigen‐specific effector T‐helper type 2 (Th2) cells, Th1 cells, or the recently defined Th17 cells that are associated with the clinical features and disease progression. In order to identify crucial processes in the pathogenesis of these diseases it is critical to understand how the development of these T cells occurs. The phenotype of a polarized T‐cell that differentiates from a naïve precursor is determined by the complex interaction of antigen‐presenting cells with naïve T cells and involves a multitude of factors, including the dominant cytokine environment, costimulatory molecules, type and load of antigen presented and a plethora of signaling cascades. The decision to take the immune response in a certain direction is not made by one signal alone, instead many different elements act synergistically, antagonistically and through positive feedback loops to activate a Th1, Th2, or Th17 immune response. The elucidation of the mechanisms of selection of T‐cell phenotype will facilitate the development of therapeutic strategies to intervene in the development of deleterious T‐cell responses. This review will focus on the pathways and key factors responsible for the differentiation of the various subsets of effector CD4 T cells. We will primarily discuss what is known of the Th1 and Th2 differentiation pathways, while also reviewing the emerging research on Th17 differentiation.
Predicting weed distribution at the landscape scale: using naturalized Brassica as a model system
Authors: Peltzer D. A , Ferriss S , FitzJohn R. G. 
Published: November 2007

Summary

Quantifying and predicting the distribution of naturalized plant species is a major concern for weed risk assessment and understanding the potential impacts of gene‐flow between crop species and feral or naturalized populations.
We developed a rapid field assessment to quantify the distribution of naturalized Brassica populations at the landscape scale, using the Canterbury Plains region of New Zealand as a model system. Internationally, brassicas are one of the most widely cultivated crops, and have well‐documented problems of crop escapes, gene‐flow and hybridization with wild relatives. Brassicas are cultivated intensively in the study system for both seed production and forage, are widely naturalized and have raised concerns for gene‐flow from feral populations to cultivated varieties.
Generalized linear models (GLM) were constructed in order to predict the presence–absence of brassicas using survey data of naturalized populations located in 50 3 × 3 km plots. This model was validated subsequently both by ground‐truthing predicted presence–absence in a second field survey, and by comparing cumulative probability distributions from a presence‐only botanical survey.
The best model produced from the field survey predicted naturalized Brassica presence–absence robustly (r2 = 0·52) and was well validated against results from the presence‐only survey carried out in the same year. Results from the second field survey during a different growing season did not match predictions from the original model, suggesting that strong between‐year differences influence large‐scale Brassica distribution. The differences between years were driven by an overall increase in the prevalence of brassicas over the course of the study that was not associated with any predictive variable or climate.
Synthesis and applications. These results have important implications both for developing models of species distribution and for predicting gene‐flow risk at the landscape scale. Despite constructing a model that was subsequently validated from presence‐only data in one year, it did not predict Brassica distribution in a subsequent year; this suggests that between‐year or stochastic factors operate strongly and are a major consideration for risk assessment. Models used to predict species distributions, in general, need to account for these between‐year effects either by incorporating mechanistic processes or long‐term data.
A linear plasmid truncation induces unidirectional flagellar phase change in H:z66 positive Salmonella Typhi
Authors: Baker Stephen , Holt Kathryn , Whitehead Sally , Goodhead Ian , Perkins Tim , Stocker Bruce , Hardy Jonathan , Dougan Gordon 
Published: November 2007

SummaryThe process by which bacteria regulate flagellar expression is known as phase variation and in Salmonella enterica this process permits the expression of one of two flagellin genes, fliC or fljB, at any one time. Salmonella Typhi (S. Typhi) is normally not capable of phase variation of flagellar antigen expression as isolates only harbour the fliC gene (H:d) and lacks an equivalent fljB locus. However, some S. Typhi isolates, exclusively from Indonesia, harbour an fljB equivalent encoded on linear plasmid, pBSSB1 that drives the expression of a novel flagellin named H:z66. H:z66+S. Typhi isolates were stimulated to change flagellar phase and genetically analysed for the mechanism of variation. The phase change was demonstrated to be unidirectional, reverting to expression from the resident chromosomal fliC gene. DNA sequencing demonstrated that pBSSB1 linear DNA was still detectable but that these derivatives had undergone deletion and were lacking fljAz66 (encoding a flagellar repressor) and fljBz66. The deletion end‐point was found to involve one of the plasmid termini and a palindromic repeat sequence within fljBz66, distinct to that found at the terminus of pBSSB1. These data demonstrate that, like some Streptomyces linear elements, at least one of the terminal inverted repeats of pBSSB1 is non‐essential, but that a palindromic repeat sequence may be necessary for replication.
Apoptosis: a potential triggering mechanism of neurological manifestation in Plasmodium falciparum malaria
Authors: TOURÉ F. S. , OUWE‐MISSI‐OUKEM‐BOYER O. , BISVIGOU U. , MOUSSA O. , ROGIER C. , PINO P. , MAZIER D. , BISSER S. 
Published: November 2007

SUMMARYPlasmodium falciparum infection can lead to a life threatening disease and the pathogenetic mechanisms of severe manifestations are not fully understood. Here, we investigated the capacity of P. falciparum‐parasitized red blood cells (PRBC) from 45 children with clinical malaria to induce endothelial cell (EC) apoptosis. In all subjects, PRBC that cytoadhered to ECs could be found albeit to a variable degree. By contrast, PRBC that induce EC apoptosis were found only in nine (20%) subjects. Interestingly, children with neurological manifestations were significantly more likely to harbour apoptogenic strains. There was no quantitative relationship between the capacity of these isolates to cytoadhere and apoptosis induction. We hypothesize that P. falciparum‐encoded molecules could be responsible for apoptosis induction and therefore suggest new insights in the pathogenesis of P. falciparum malaria. Further investigations are currently in progress to determine whether these results can be confirmed and to identify putative parasite apoptogenic factors.
New therapeutic options for adult chronic immune thrombocytopenic purpura: a brief review
Authors: Panzer S. 
Published: November 2007

Background  Patients with chronic immune thrombocytopenic purpura (ITP) only require treatment if they are bleeding, or prior to scheduled operations. Patients are also treated if platelet counts are very low. Some patients become refractory, relapse or do not respond to treatment with steroids. Splenectomy is effective in raising the platelet count in most patients, but as spontaneous remission may occur even after 1 year or more, it is justified to defer splenectomy. Furthermore, splenectomy and/or first‐line treatment modalities may not suit all patients. Therefore, alternatives are desirable.Materials  This review will focus on anti‐B cell therapy with rituximab, and two thrombopoietin mimetic agents that have entered clinical trials, AMG 531 and eltrombopag. These therapeutics have been studied in patients who were refractory to first‐line treatment and/or splenectomy, and to defer splenectomy.Results  There are no controlled trials with rituximab, but clinical experience has shown a success rate of 40% to 60%. Encouraging phase 1 and 2 data have been published for both thrombopoietin mimetics; preliminary data from an open‐label extension trial with AMG 531 and from phase 3 studies with eltrombopag further confirm their efficacy.Conclusion  Clinical experience will ultimately determine the appropriate indications of these new treatments for ITP.
PHARMACOKINETICS AND PHARMACODYNAMICS OF INDOMETHACIN: EFFECTS ON CEREBRAL BLOOD FLOW IN ANAESTHETIZED SHEEP
Authors: Upton Richard N , Rasmussen Mads , Grant Cliff , Martinez Allison M , Cold Georg E , Ludbrook Guy L 
Published: November 2007

SUMMARY

Indomethacin has been used to manage raised intracranial pressure (ICP) in humans during neuroanaesthesia and neurosurgery. Indomethacin causes cerebral vasoconstriction and reduces cerebral blood flow (CBF) and, therefore, ICP.
The systemic kinetics, cerebral kinetics and cerebral dynamics of indomethacin (0.2 mg/kg) were measured and modelled using a population approach. Data were collected using an instrumented sheep preparation with raised ICP and under either isoflurane or propofol anaesthesia to parallel the clinical use of indomethacin in neurosurgery.
The systemic kinetics of indomethacin could be described by a two‐compartment model, with small distribution volumes and a clearance of 0.68 L/min. The cerebral kinetics of indomethacin could be described using a model with a cerebral distribution volume between 5 and 8 mL and a loss term of 3.3 mL/min, the latter probably representing slow diffusion across the blood–brain barrier.
The changes in CBF lagged behind the blood concentrations of indomethacin. Indirect response models with turnover times of 1.70–4.08 min were generally better able to describe the effect of indomethacin on CBF than effect compartment models.
There was a non‐linear concentration–effect relationship, with the maximum possible reduction in CBF being to 73–74% of baseline.
The data and model support the concept of indomethacin having limited uptake into the brain, with its effect on CBF being the result of its action on the endothelium, where it indirectly modifies the turnover of a compound regulating vascular tone.
PROTECTION BY AND ANTI‐OXIDANT MECHANISM OF BERBERINE AGAINST RAT LIVER FIBROSIS INDUCED BY MULTIPLE HEPATOTOXIC FACTORS
Authors: Zhang Ben‐Jian , Xu Dan , Guo Yu , Ping Jie , Chen Liao‐bin , Wang Hui 
Published: November 2007

SUMMARYThe aim of the present study was to investigate the effect and mechanism of berberine, an alkaloid extracted from the traditional Chinese medicine coptis, on rat liver fibrosis induced by multiple hepatotoxic factors.Male Wistar rats were separated into five groups, a normal control group, a fibrotic control group and fibrotic groups treated with three different doses of berberine. The fibrotic models were established by introduction of multiple hepatotoxic factors, including CCl4, ethanol and high cholesterol. Rats in the treatment groups were administered 50, 100 or 200 mg/kg berberine, intragastrically, daily for 4 weeks. Serum levels of alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST), hepatic activity of superoxide dismutase (SOD) and hepatic malondialdehyde (MDA) and hepatic hydroxyproline (Hyp) content were determined. Liver biopsies were obtained for histological and immunohistochemical studies to detect the expressions of a‐smooth muscle actin (SMA) and transforming growth factor (TGF)‐b1.The results showed that, compared with the fibrotic control group, serum levels of ALT and AST and hepatic content of MDA and Hyp were markedly decreased, but the activity of hepatic SOD was significantly increased in berberine‐treated groups in a dose‐dependent manner. In addition, histopathological changes, such as steatosis, necrosis and myofibroblast proliferation, were reduced and the expression of a‐SMA and TGF‐b1 was significantly downregulated in the berberine‐treated groups (P < 0.01).These results suggest that berberine could be used to prevent experimental liver fibrosis through regulation of the anti‐oxidant system and lipid peroxidation.
SYSTEMIC DELIVERY OF ADULT STEM CELLS IMPROVES CARDIAC FUNCTION IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: De Macedo Braga Luisa MG , Rosa Kaleizu , Rodrigues Bruno , Malfitano Christiane , Camassola Melissa , Chagastelles Pedro , Lacchini Silvia , Fiorino Patricia , De Angelis Kátia , D’Agord Schaan Beatriz , Irigoyen Maria C , Beyer Nardi Nance 
Published: November 2007

SUMMARY

Heart regeneration after myocardial infarction (MI) can occur after cell therapy, but the mechanisms, cell types and delivery methods responsible for this improvement are still under investigation. In the present study, we evaluated the impact of systemic delivery of bone marrow cells (BMC) and cultivated mesenchymal stem cells (MSC) on cardiac morphology, function and mortality in spontaneously hypertensive rats (SHR) submitted to coronary occlusion.
Female syngeneic adult SHR, submitted or not (control group; C) to MI, were treated with intravenous injection of MSC (MI + MSC) or BMC (MI + BM) from male rats and evaluated after 1, 15 and 30 days by echocardiography. Systolic blood pressure (SBP), functional capacity, histology, mortality rate and polymerase chain reaction for the Y chromosome were also analysed.
Myocardial infarction induced a decrease in SBP and BMC, but not MSC, prevented this decrease. An improvement in functional capacity and ejection fraction (38 ± 4, 39 ± 3 and 58 ± 2% for MI, MI + MSC and MI + BM, respectively; P < 0.05), as well as a reduction of the left ventricle infarcted area, were observed in rats from the MI + BM group compared with the other three groups. Treated animals had a significantly reduced lesion tissue score. The mortality rate in the C, MI + BM, MI + MSC and MI groups was 0, 0, 16.7 and 44.4%, respectively (P < 0.05 for the MI + MSC and MI groups compared with the C and MI + BM groups).
The results of the present study suggest that systemic administration of BMC can improve left ventricular function, functional capacity and, consequently, reduce mortality in an animal model of MI associated with hypertension. We speculate that the cells transiently home to the myocardium, releasing paracrine factors that recruit host cells to repair the lesion.
Preventive effect of hochu‐ekki‐to, a Japanese herbal medicine, on bleomycin‐induced lung injury in mice
Authors: TAJIMA Shunji , BANDO Masashi , YAMASAWA Hideaki , OHNO Shoji , MORIYAMA Hiroshi , TERADA Masaki , TAKADA Toshinori , SUZUKI Eiichi , GEJYO Fumitake , SUGIYAMA Yukihiko 
Published: November 2007

Objective:  Pulmonary fibrosis is thought to be closely associated with the T‐helper type‐2 (Th2) immune response. Recent studies have shown that hochu‐ekki‐to (TJ‐41), a Japanese herbal medicine, may correct the Th1/Th2 imbalance skewed to Th2. The present study was designed to investigate the preventive effect of TJ‐41 on the development of bleomycin (BLM)‐induced lung injury in mice.Methods:  Female C57BL/6 mice were divided into a group given ordinary feed and another group given the same feed plus TJ‐41 mixed in at a dose of 1 g/kg/day. Both groups were maintained on this diet for 8 weeks before and 5 weeks after administration of 2 mg/kg BLM intratracheally.Results:  Mortality after BLM‐induced lung injury was significantly lower in the TJ‐41‐treated mice. The hydroxyproline content and fluid content in the lung on day 35 was significantly lower in the TJ‐41‐treated mice. Histologically, TJ‐41 reduced the number of infiltrating cells, thus ameliorating the destruction of the lung architecture, and attenuated the lung fibrosis score. Furthermore, TJ‐41 inhibited the expression of the interleukin‐5/interferon‐γ mRNA ratio in the lung on day 7.Conclusions:  Treatment with TJ‐41 partially prevented experimental lung fibrosis through the correction of the Th1/Th2 imbalance skewed to Th2.
BODE score is a useful predictor of hospital admission in rural patients with chronic obstructive pulmonary disease
Authors: MCKELLAR Alice , COTTRELL W. Neil , WHELAN Anthony 
Published: November 2007

Background and objective:  COPD is a chronic illness with frequent episodic exacerbations that require admission to hospital. The aim of this study was to identify risk factors (or predictors) for hospital admission in a sample of rural COPD patients.Methods:  COPD patients from the Goulburn and Crookwell areas of New South Wales, Australia, were included in the study. Patients were divided into two groups: those with two or fewer admissions, and those with three or more admissions in the last year. Patient interviews were conducted, and data were collected on demographics, consumption of health resources, COPD severity measures (BODE score) and quality of life.Results:  There were 32 patients recruited with a median age of 68 years, and 21 (65.6%) were male. There were no significant differences in risk factors (or predictors) identified between the two groups. A statistical difference was found between the two groups, with patients with three or more hospital admissions having a higher BODE score (P = 0.004), poorer quality‐of‐life score (P = 0.015) and reduced exercise tolerance (P = 0.001).Conclusions:  In this small sample of COPD patients, there were no clear differences in terms of risk factors for COPD admission between the two groups. The BODE score was found to be a useful predictor of disease severity and likelihood of hospital admission.