bluuebunny/crossref_metadata_2025 huggingface dataset:
Mycobacterium marinum
Infection of Adult Zebrafish Causes Caseating Granulomatous Tuberculosis and Is Moderated by Adaptive Immunity
Authors: Swaim Laura E. , Connolly Lynn E. , Volkman Hannah E. , Humbert Olivier , Born Donald E. , Ramakrishnan Lalita
Published: October 2006

The zebrafish, a genetically tractable model vertebrate, is naturally susceptible to tuberculosis caused by
Mycobacterium marinum
, a close genetic relative of the causative agent of human tuberculosis,
Mycobacterium tuberculosis
. We previously developed a zebrafish embryo-
M. marinum
infection model to study host-pathogen interactions in the context of innate immunity. Here, we have constructed a flowthrough fish facility for the large-scale longitudinal study of
M. marinum
-induced tuberculosis in adult zebrafish where both innate and adaptive immunity are operant. We find that zebrafish are exquisitely susceptible to
M. marinum
strain M. Intraperitoneal injection of five organisms produces persistent granulomatous tuberculosis, while the injection of ∼9,000 organisms leads to acute, fulminant disease. Bacterial burden, extent of disease, pathology, and host mortality progress in a time- and dose-dependent fashion. Zebrafish tuberculous granulomas undergo caseous necrosis, similar to human tuberculous granulomas. In contrast to mammalian tuberculous granulomas, zebrafish lesions contain few lymphocytes, calling into question the role of adaptive immunity in fish tuberculosis. However, like
rag1
mutant mice infected with
M. tuberculosis
, we find that
rag1
mutant zebrafish are hypersusceptible to
M. marinum
infection, demonstrating that the control of fish tuberculosis is dependent on adaptive immunity. We confirm the previous finding that
M. marinum
ΔRD1 mutants are attenuated in adult zebrafish and extend this finding to show that ΔRD1 predominantly produces nonnecrotizing, loose macrophage aggregates. This observation suggests that the macrophage aggregation defect associated with ΔRD1 attenuation in zebrafish embryos is ongoing during adult infection.
Disparate Immunoregulatory Potentials for Double-Negative (CD4−CD8−) αβ and γδ T Cells from Human Patients with Cutaneous Leishmaniasis
Authors: Antonelli Lis R. V. , Dutra Walderez O. , Oliveira Ricardo R. , Torres Karen C. L. , Guimarães Luiz H. , Bacellar Olivia , Gollob Kenneth J.
Published: October 2006

Although most T lymphocytes express the αβ T-cell receptor and either CD4 or CD8 molecules, a small population of cells lacking these coreceptors, CD4−CD8−(double negative [DN]) T cells, has been identified in the peripheral immune system of mice and humans. To better understand the role that this population may have in the human immune response againstLeishmaniaspp., a detailed study defining the activation state, cytokine profile, and the heterogeneity of DN T cells bearing αβ or γδ T-cell receptors was performed with a group of well-defined cutaneous leishmaniasis patients. Strikingly, on average 75% of DN T cells from cutaneous leishmaniasis patients expressed the αβ T-cell receptor, with the remainder expressing the γδ receptor, while healthy donors displayed the opposite distribution with ∼75% of the DN T cells expressing the γδ T-cell receptor. Additionally, αβ DN T cells from cutaneous leishmaniasis patients are compatible with previous antigen exposure and recent activation. Moreover, while αβ DN T cells fromLeishmania-infected individuals present a proinflammatory cytokine profile, γδ DN T cells express a regulatory profile exemplified by interleukin-10 production. The balance between these subpopulations could allow for the formation of an effective cellular response while limiting its pathogenic potential.
Immunization with LiveNeisseria lactamicaProtects Mice against Meningococcal Challenge and Can Elicit Serum Bactericidal Antibodies
Authors: Li Yanwen , Zhang Qian , Winterbotham Megan , Mowe Eva , Gorringe Andrew , Tang Christoph M.
Published: October 2006

Natural immunity againstNeisseria meningitidisis thought to develop following nasopharyngeal colonization with this bacterium or other microbes expressing cross-reactive antigens.Neisseria lactamicais a commensal of the upper respiratory tract which is often carried by infants and young children; epidemiological evidence indicates that colonization with this bacterium can elicit serum bactericidal activity (SBA) againstNeisseria meningitidis, the most validated correlate of protective immunity. Here we demonstrate experimentally that immunization of mice with liveN. lactamicaprotects animals against lethal meningococcal challenge and that some, but not all, strains ofN. lactamicaelicit detectable SBA in immunized animals regardless of the serogroup ofN. meningitidis. While it is unlikely that immunization with liveN. lactamicawill be implemented as a vaccine against meningococcal disease, understanding the basis for the induction of cross-protective immunity and SBA should be valuable in the design of subunit vaccines for the prevention of this important human infection.
Incidence of hand eczema in female Swedish hairdressers
Authors: Lind Marie-Louise , Albin Maria , Brisman Jonas , Kronholm Diab Kerstin , Lillienberg Linnéa , Mikoczy Zoli , Nielsen Jörn , Rylander Lars , Torén Kjell , Meding Birgitta
Published: October 2006

Objective:To estimate the occurrence of hand eczema in hairdressers in Sweden.

Methods:The occurrence of hand eczema was estimated in a Swedish longitudinal retrospective cohort study including all female graduates from vocational schools for hairdressers from 1970 to 1995. A stratified sample from the general population acted as controls. A self-administered questionnaire including questions on the occurrence of hand eczema, skin atopy, working periods and number of hair treatments performed per week was sent to the participants. Incidence rate ratios (IRRs) of hand eczema were estimated.

Results:The incidence rate of hand eczema in hairdressers was 23.8 cases/1000 person-years, whereas in hairdressers who were aged <25 years it was 37.1/1000 person-years. The corresponding IRR for hairdressers compared with controls was 2.5 (95% confidence interval (CI) 2.2 to 2.8), and that for younger hairdressers was 3.1 (95% CI 2.6 to 3.5). The mean age at onset of hand eczema was 21.6 years for hairdressers and 21.2 years for controls. The 1-year prevalence of hand eczema was 18.0% for hairdressers and 12.1% for controls. A large number of hair treatments involving exposure to skin irritants and sensitisers were reported. The incidence rate of hand eczema was higher among individuals with a history of childhood eczema, both for hairdressers and for controls, giving an (age-adjusted) IRR of 1.9 and 2.2, respectively. The attributable fraction of hand eczema from skin atopy was 9.6%. A synergistic effect of skin atopy and hairdressing was found on the occurrence of hand eczema. The relative excess risk due to interaction was 1.21 (95% CI 0.21 to 2.21; p = 0.01).

Conclusion:Hairdressers are highly exposed to skin-damaging substances. The self-reported incidence of hand eczema was substantially higher in female hairdressers than in controls from the general population and than that found previously in register-based studies. For many individuals, onset of hand eczema occurs early in life. Only about 10% of the hand eczema cases among hairdressers would be prevented if no one with skin atopy entered the trade.
Bias in occupational epidemiology studies
Authors: Pearce Neil , Checkoway Harvey , Kriebel David
Published: October 2006

The design of occupational epidemiology studies should be based on the need to minimise random and systematic error. The latter is the focus of this paper, and includes selection bias, information bias and confounding. Selection bias can be minimised by obtaining a high response rate (and by appropriate selection of the control group in a case-control study). In general, it is important to ensure that information bias is minimised and is also non-differential (for example, that the misclassification of exposure is not related to disease status) by collecting data in a standardised manner. A major concern in occupational epidemiology studies usually relates to confounding, because exposure has not been randomly allocated, and the groups under study may therefore have different baseline disease risks. For each of these types of bias, the goal should be to avoid the bias by appropriate study design and/or appropriate control in the analysis. However, it is also important to attempt to assess the likely direction and strength of biases that cannot be avoided or controlled.
Occupational exposure to asbestos and man-made vitreous fibres and risk of lung cancer: a multicentre case-control study in Europe
Authors: Carel Rafael , Olsson Ann C , Zaridze David , Szeszenia-Dabrowska Neonila , Rudnai Peter , Lissowska Jolanta , Fabianova Eleonora , Cassidy Adrian , Mates Dana , Bencko Vladimir , Foretova Lenka , Janout Vladimir , Fevotte Joelle , Fletcher Tony , Mannetje Andrea ’t , Brennan Paul , Boffetta Paolo
Published: October 2006

Objectives:To investigate the contribution of occupational exposure to asbestos and man-made vitreous fibres (MMVF) to lung cancer in high-risk populations in Europe.

Methods:A multicentre case-control study was conducted in six Central and Eastern European countries and the UK, during the period 1998–2002. Comprehensive occupational and sociodemographic information was collected from 2205 newly diagnosed male lung cancer cases and 2305 frequency matched controls. Odds ratios (OR) of lung cancer were calculated after adjusting for other relevant occupational exposures and tobacco smoking.

Results:The OR for asbestos exposure was 0.92 (95% CI 0.73 to 1.15) in Central and Eastern Europe and 1.85 (95% CI 1.07 to 3.21) in the UK. Similar ORs were found for exposure to amphibole asbestos. The OR for MMVF exposure was 1.23 (95% CI 0.88 to 1.71) with no evidence of heterogeneity by country. No synergistic effect either between asbestos and MMVF or between any of them and smoking was found.

Conclusion:In this large community-based study occupational exposure to asbestos and MMVF does not appear to contribute to the lung cancer burden in men in Central and Eastern Europe. In contrast, in the UK the authors found an increased risk of lung cancer following exposure to asbestos. Differences in fibre type and circumstances of exposure may explain these results.
NATURE OF THE SINGULARITIES IN HIGHER-DIMENSIONAL HUSAIN SPACE–TIME
Authors: PATIL K. D. , ZADE S. S.
Published: October 2006

We generalize the earlier studies on the spherically symmetric gravitational collapse in four-dimensional space–time to higher dimensions. It is found that the central singularities may be naked in higher dimensions but depend sensitively on the choices of the parameters. These naked singularities are found to be gravitationally strong that violate the cosmic censorship hypothesis.
INTERIOR KERR SOLUTIONS WITH THE NEWMAN–JANIS ALGORITHM STARTING WITH STATIC PHYSICALLY REASONABLE SPACE–TIMES
Authors: VIAGGIU STEFANO
Published: October 2006

We present a simple approach for obtaining Kerr interior solutions with the help of the Newman–Janis algorithm (NJA) starting with static space–times describing physically sensible interior Schwarzschild solutions. In this context, the Darmois–Israel (DI) junction conditions are analyzed. Starting from the incompressible Schwarzschild solution, a class of Kerr interior solutions is presented, together with a discussion of the slowly rotating limit. The energy conditions are discussed for the solutions so obtained. Finally, the NJA algorithm is applied to the static, anisotropic, conformally flat solutions found by Stewart leading to interior Kerr solutions with oblate spheroidal boundary surfaces.
LARGE DYNAMICAL SYMMETRY OF QUASI-SPHERICAL GRAVITATIONAL COLLAPSE WITH RADIAL AND TANGENTIAL PRESSURES AND ANISOTROPY AND INHOMOGENEITY OF SPACE–TIME
Authors: CHAKRABORTY SUBENOY , CHAKRABORTY SANJUKTA
Published: October 2006

A detailed study of higher-dimensional quasi-spherical gravitational collapse with radial and tangential stresses has been done and the role of initial data, anisotropy and inhomogeneity has been investigated in determining the end state of collapse. By linear scaling the initial data set and the area radius, it is found that the dynamics of quasi-spherical collapse remains invariant. In other words, the linear transformation identifies an equivalence class of data sets for which physical parameters like density, pressures (radial and tangential), shear remain invariant and the final state of collapse is identical (black hole or naked singularity). Finally, the role of anisotropy and inhomogeneity has been studied by proving some propositions.
A HIDDEN MARKOV APPROACH TO THE FORWARD PREMIUM PUZZLE
Authors: ELLIOTT ROBERT J. , HAN BING
Published: October 2006

A Hidden Markov Chain (HMC) is applied to study the forward premium puzzle. The weekly quotient of the interest rate differential divided by the log exchange rate change is modeled as a Hidden Markov process. Compared with existing standard approaches, the Hidden Markov approach allows a detailed analysis of the puzzle on a day-to-day basis while taking into full account the presence of noise in the observations. Two and three state models are investigated. A three-state HMC model performs better than two-state models. Application of the three-state model reveals that the above quotient is mostly zero, and hence leads to the rejection of the uncovered interest rate parity hypothesis.
FAST AND REALISTIC RENDERING OF DEFORMABLE VIRTUAL CHARACTERS USING IMPOSTOR AND STENCIL BUFFER
Authors: CHOW S. K. , CHAN K. L.
Published: October 2006

Algorithms for rendering numerous virtual characters often achieve interactive frame rate by reducing the computation load. The major drawback of this approach is that the rendering quality is degraded. This project aims to develop a fast rendering scheme that can be used on realistic virtual human characters. We have made two contributions. Firstly, we have created a high quality human model and designed three basic deformation methods. The deformation of each body part is composed of the basic deformation methods. Our aim is to generate visually similar deformed and seamless character efficiently. Rendering of numerous characters at high frame rate can be maintained by using impostor. It is well known that impostor has the visibility problem. Secondly, to correct the visibility problem, we propose to incorporate the depth information to each character by using stencil buffer and bounding box. Our rendering scheme compares favorably, in terms of the frame rate and the rendering quality, with multi-layered impostor.
RELIEF TEXTURE MAPPING ON FIELD PROGRAMMABLE GATE ARRAY
Authors: LI XIAOYING , WU ENHUA
Published: October 2006

Relief texture mapping is an image-based rendering technique which can successfully support the representation of 3D surface details and view motion parallax. It has the potential to significantly increase visual realism of rendered geometry while keeping system load constant. In this paper, FPGA (Field Programmable Gate Array) chip technology is applied to this three-dimensional image warping method. A relief texture mapping system has been implemented on a reprogrammable and reconfigurable FPGA board. The algorithm is optimized for the specific architecture and the framework is customized for circuit resources, which can be flexibly changed for other structures. In our design, we take advantage of inherent parallelism of the algorithm by concatenating multiple warping engines and well organizing data in memory space. Experimental results show high image quality with improved rendering speed.
DESIGN AND IMPLEMENTATION OF WAVELET-DOMAIN VIDEO COMPRESSION USING MULTIRESOLUTION MOTION ESTIMATION AND COMPENSATION
Authors: CAI WEITING , ADJOUADI MALEK
Published: October 2006

Video compression techniques have been applied routinely in order to conserve storage space and minimize bandwidth utilization in various video applications. To reduce inter-pixel redundancies inside and between video frames, video codecs (coder/decoder or compression/decompression) are mainly characterized by applying motion estimation and motion compensation (MEMC) in combination with discrete cosine transform (DCT). However, blocking artifacts are obvious from the block-based motion estimation and transformation, especially at low bit rates. Due to the intrinsic advantages of multiresolution and scalability of discrete wavelet transform (DWT), video compression techniques have been infused with exciting prospects by the beneficial integration of motion estimation and wavelet transformation. The contributions of this paper are in (1) proposing a design architecture of the wavelet-domain encoder and decoder; (2) implementing the multiresolution motion estimation and compensation method; and in (3) realizing the dynamic entropy encoding and decoding, so as to achieve more efficient video compression than the conventional spatial domain methods for low bit rate applications without the annoying blocking artifacts.
Psychological stress impairs Na+-dependent glucose absorption and increases GLUT2 expression in the rat jejunal brush-border membrane
Authors: Boudry Gaëlle , Cheeseman Christopher I. , Perdue Mary H.
Published: October 2006

Chronic psychological stress impacts many functions of the gastrointestinal tract. However, the effect of stress on nutrient absorption is poorly documented. This study was designed to investigate glucose transporters in rats submitted to different periods of water-avoidance stress (WAS). Rats were subjected to WAS (1 h/day) for 1, 5, or 10 consecutives days. Four hours after the last WAS session, rats were killed and segments of jejunum were mounted in Ussing chambers to study electrophysiological properties of the jejunum and Na+-dependent glucose absorption kinetics. Mucosa was obtained to prepare brush-border membrane vesicles (BBMV) used to measure [14C]fructose uptake as well as sodium-glucose transporter 1 (SGLT-1) and GLUT2 expression by Western blot analysis. Exposure of animals to WAS induced a decrease in Na+-dependent glucose absorption Vmaxafter 1, 5, and 10 days without any change in SGLT-1 expression. Potential difference across the jejunum was decreased for all stressed groups. Furthermore, we observed an increase in phloretin-sensitive uptake of [14C]fructose by BBMV after 1, 5, or 10 days of WAS, which was not present in control animals. This suggested the abnormal appearance of GLUT2 in the brush border, which was confirmed by Western blot analysis. We concluded that psychological stress induces major changes in glucose transport with a decrease in Na+-dependent glucose absorption and an increase in GLUT2 expression at the brush-border membrane level.
Obesity and asthma: lessons from animal models
Authors: Shore Stephanie A.
Published: October 2006

Epidemiological data indicate that obesity is a risk factor for asthma. These data are supported by observations in several murine models of obesity. Ob/ob, db/db, and Cpefatmice each exhibit innate airway hyperresponsiveness, a characteristic feature of asthma. These mice also respond more vigorously to common asthma triggers, including ozone. Here we discuss the implications of these data with respect to several mechanisms proposed to explain the relationship between obesity and asthma: 1) common etiologies; 2) comorbidities; 3) mechanical factors; and 4) adipokines. We focus on the role of adipokines, especially TNF-α, IL-6, leptin, and adiponectin. Understanding the mechanistic basis for the relationship between obesity and asthma may lead to novel therapeutic strategies for treatment of the obese asthmatic subject.
Progression of Dental Caries and Tooth Loss between the Third and Fourth Decades of Life: A Birth Cohort Study
Authors: Broadbent J.M. , Thomson W.M. , Poulton R.
Published: October 2006

The majority of what is known of the experience of dental caries among adults is from cross-sectional studies, and there are surprisingly few population-level longitudinal studies of dental caries among adults. Dental examinations were conducted at age 26 and again at age 32 among participants in a longstanding prospective study of a birth cohort born in Dunedin (New Zealand) in 1972/1973. Some 901 individuals (88.8%) were dentally examined at both ages. The mean number of remaining teeth and tooth surfaces fell between 26 and 32, reflecting ongoing tooth loss. The overall prevalence of caries rose from 94.9 to 96.8%, while there were greater increases in the proportion with caries-associated tooth loss (from 10.8 to 22.8%). Caries experience was greatest in the molar teeth and upper premolars, and was lowest in the lower anterior teeth. The mean crude caries increment (CCI) was 5.0 surfaces (SD 6.6); 681 (75.5%) experienced 1+ CCI, and the mean CCI among those individuals was 6.6 surfaces (SD 6.9). Substantial dental caries and tooth loss experience occur as people move from the third into the fourth decade of life.
Dietary Patterns Related to Caries in a Low-Income Adult Population
Authors: Burt Brian A. , Kolker Justine L. , Sandretto Anita M. , Yuan Ying , Sohn Woosung , Ismail Amid I.
Published: October 2006

The aim of this study was toexamine the relationship between dietary patterns and caries experience in a representative group of low-income African-American adults. Participants were residents of Detroit, Michigan, with household incomes below 250% of the federally-established poverty level (n = 1,021). Dietary histories were obtained by trained interviewers in face-to-face interviews with the adult participants, using the Block 98.2® food frequency questionnaire. Caries was measured by the ICDAS criteria (International Caries Detection and Assessment System). There were 200 dietary records whose data were judged to be invalid; these participants were omitted from the dietary analyses to leave n = 821. Factor analysis identified patterns of liquid and solid food consumption, and the resulting factor scores were used as covariates in multivariable linear regression. Caries was extensive, with 82.3% of the 1,021 participants (n = 839) having at least one cavitated lesion. Nearly three quarters of the adult participants were overweight or obese. This population had severe caries, poor oral hygiene, and diets that are high in sugars and fats and low in fruits and vegetables. Apart from tap water, the most frequently consumed food item by adults of all ages was soft drinks; 19% of all energy from sugar came from soft drinks alone. In both the bivariate analyses and in the regression model, frequency of soft drink consumption and the presence of gingival plaque deposits were significantly associated with caries. Interventions to promote oral health are unlikely to be successful without improvements in the social and physical environment.
The Effectiveness of Hospitalization in the Treatment of Paediatric Idiopathic Headache Patients
Authors: Lanzi G. , D’Arrigo S. , Termine C. , Rossi M. , Ferrari-Ginevra O. , Mongelli A. , Millul A. , Beghi E.
Published: October 2006

Background: Headache is a disease that has a high social impact in the paediatric as well as in the adult population, often resulting in a significant reduction in the young patient’s quality of life, reflected primarily in a greater number of days off school and increasingly frequent recourse to symptomatic drugs. The idea for this study came from the clinical impression that some paediatric headache patients might benefit more from inpatient than outpatient care. Aim: The aim of our study was to compare the effectiveness of hospitalization to outpatient care of patients with newly diagnosed frequent and disabling headache. Methods: A pragmatic randomized open-label trial was conducted at the Child Neurology Clinic of the University of Pavia, Italy. Children and adolescents with a 2- to 6-month moderate-to-severe migraine or tension-type headache history were randomized to hospital admission or outpatient assessment and followed for 6 months. The efficacy of the two therapeutic strategies was measured by counting the number of responders in each arm. Other end points included the mean frequency and duration of attacks, the number of drug prescriptions taken to control pain, and the number of patients and physicians expressing satisfaction with treatment. Results: The study population included 27 girls and 23 boys aged 8 through 18 years with migraine (23 cases) or tension-type headache (27 cases). Compared to outpatient assessment, hospital admission was correlated to a significant increase in the number of responders: 0 vs. 44% (1 month), 0 vs. 68% (3 months), and 12 vs. 68% (6 months). The mean frequency and duration of attacks were significantly lower in hospitalized patients (p < 0.0001). Hospitalization was correlated with a significant reduction of patients with severe headache (p < 0.005), a reduction of drug use, and a higher number of satisfied patients and physicians (p < 0.05). Logistic regression analysis confirmed the higher responder rate among hospitalized patients after adjusting for age, sex, diagnosis, and headache characteristics or admission. Conclusions: We think hospitalization reduces the emotional mechanisms that provoke stress in children and often induce or favour headache attacks. If these mechanisms can be interrupted, the management of disease may become easier and with enduring benefits.
Semicentennial Tribute to the Ingenious Neurobiologist Christfried Jakob (1866–1956). 1. Works from Germany and the First Argentina Period, 1891–1913
Authors: Triarhou Lazaros C. , del Cerro Manuel
Published: October 2006

This study, and the companion paper that follows, pays homage to the life and work of Christfried (also Christian or Christofredo) Jakob, a German-born neuropathologist who adopted Argentina as his country of vocation. Rated by von Economo and Koskinas among the three most important pre-1925 cortical neuro-anatomists, alongside Ramón y Cajal, Jakob is little known in the English literature. He has left an impressive record of publications, 30 richly illustrated monographs and 200 articles that span over a vast array of neurological themes, including cortical development and evolution, and the visceral brain. The present paper reviews works from his German years and the first visit to Argentina in 1899–1910. The companion paper covers his works (all in Spanish) during his ‘second Argentina period’, after 1913.
Semicentennial Tribute to the Ingenious Neurobiologist Christfried Jakob (1866–1956). 2. Publications from the Second Argentina Period, 1913–1949
Authors: Triarhou Lazaros C. , del Cerro Manuel
Published: October 2006

Christofredo (also Christfried or Christian) Jakob is considered the father of neurology, neurobiology and forensic histopathology in Argentina, where he initially worked between 1899–1910 and then from 1913 onwards. He held professorships of neurobiology at the Faculty of Humanities and Educational Sciences of the University of La Plata and of anatomy and biology at the University of Buenos Aires, and established one of the most important neuropathological laboratories in South America. In the latter phase of his career, Jakob published important works on the pathological anatomy of neurological and neuropsychiatric disorders and formalized ideas on consciousness and neurophilosophy.
A Case of 46,X,der(X)t(X;X)(q22.1;p11) Xq22.1→Xqter in a 12-Year-Old Girl with Premature Ovarian Failure
Authors: Merhi Z.O. , Roberts J.L. , Awonuga A.O.
Published: October 2006

Premature ovarian failure due to Xp duplication and Xq deletion has been reported in four patients, the youngest of whom was 18 years old. The diagnosis has been made with new techniques for genetic analysis, such as comparative genomic hybridization and fluorescence in situ hybridization. We report the youngest case (a 12-year-old who presented with irregular menses), of premature ovarian failure due to Xp duplication and Xq deletion and the first with 46,X,der(X)t(X;X)(q22.1;p11). The diagnosis was made using C-banding and fluorescent in situ hybridization with locus-specific probes. This case highlights the need to use advanced genetic strategies to determine karyotypic and phenotypic abnormalities.
Airborne Pollen Concentrations and the Incidence of Allergic Asthma and Rhinoconjunctivitis in Northern Italy from 1992 to 2003
Authors: Ridolo E. , Albertini R. , Giordano D. , Soliani L. , Usberti I. , Dall’Aglio P.P.
Published: October 2006

Background: Aeroallergens and the environment play an important role in the pathogenesis of respiratory allergies. In a 12-year study carried out in Northern Italy (geographic area of Parma), the effects of airborne pollen and meteorological conditions on the incidence of allergic asthma and rhinoconjunctivitis were evaluated. Patients and Methods: Among 9,060 subjects examined for respiratory pathologies at our Allergy Unit, Parma Hospital, Italy, from 1992 to 2003, only 1,054 positive to only one type of inhalant allergen in the skin prick test were studied, to avoid bias of cross-reactivity. Allergy and clinical aspects were compared with the duration of the pollination period, and peaks and total concentrations of airborne pollen. Results: Our data showed a significantly growing trend of allergy to mites, pets and birch pollen and a significant increase in asthma, and a significantly decreasing trend of positive reactions to grasses and a decrease in rhinoconjunctivitis. At the same time, there was a significant decrease in total pollen counts, concentration peaks and pollination period of grasses. A significant increase was only observed in ragweed and ash-olive total and peak pollen concentrations. Conclusions: Significant correlations between the increasing incidence in asthma and allergy to mites, pets and birch pollen are shown. The decrease in the total pollen count and concentration peaks of grass pollen was correlated to the decreasing trend of rhinoconjunctivitis. The trend of increasing concentrations of ash-olive and ragweed pollen was not accompanied by an increase in the related allergy.
A Randomized Controlled Clinical Trial to Evaluate the Efficacy, Safety, Cost-Effectiveness and Effect on PAI-1 Levels of the Three Low-Molecular-Weight Heparins – Enoxaparin, Nadroparin and Dalteparin
Authors: Shafiq N. , Malhotra S. , Pandhi P. , Sharma N. , Bhalla A. , Grover A.
Published: October 2006

Background: Comparative data for efficacy and safety between various low-molecular-weight heparins (LMWHs) in patients with unstable angina is not available. The present study was conducted to compare the efficacy, safety, cost-effectiveness and effects on plasminogen activator inhibitor-1 (PAI-1) levels of three LMWHs – enoxaparin, nadroparin and dalteparin. Methods: The study was a prospective, randomized, comparative, open with blinded endpoints (PROBE design) assessment with a 30-day follow-up. The primary endpoint of efficacy was a composite of cardiovascular death, myocardial infarction, recurrent angina and need for intervention. Cost-effectiveness was calculated by calculating the incremental cost-effectiveness ratio. Plasma PAI-1 levels were estimated by ELISA. Results: A total of 150 patients were available for intention-to-treat analysis. There was no significant difference at 30 days in the primary endpoint or in any of the individual components in the three groups. The secondary endpoint of silent ischemia was also not significantly different. Adverse events were similar in the three groups. The PAI-1 levels were not significantly different in the three groups. The total cost of treatment in the three groups was similar. Conclusion: Any of the three LMWHs evaluated in this study were similar with respect to efficacy, safety, PAI-1 levels and cost-effectiveness.
Spontaneous Intracranial Hypotension: Correlation of Imaging Findings with Clinical Features
Authors: Wiesemann Elke , Berding Georg , Goetz Friedrich , Windhagen Anja
Published: October 2006

Background: Spontaneous intracranial hypotension (SIH) is increasingly recognized as a clinically variable and likely underdiagnosed syndrome caused by non-traumatic CSF leaks. The aim of this study was to correlate the findings of imaging studies – magnetic resonance imaging (MRI), radionuclide cisternography – with clinical features and CSF pressure in SIH in order to improve the diagnostic yield and management in patients with SIH. Methods: Clinical case study of 10 consecutive cases of SIH, MRI, radio-isotope cisternography. Results: 5 out of 10 patientshad unusual clinical symptoms of SIH(2 subdural haematomas, 1 gait ataxia, 1 tinnitus, 1 haemodialysis-associated headache). In 7 patients pachymeningeal gadolinium enhancement was detected in MRI accompanied by a reduced CSF opening pressure. In contrast, the 3 patients with normal MRI also had a normal CSF pressure. Radio-isotope cisternography was abnormal in all patients tested. There was no correlation between the severity of clinical symptoms and MRI or radionuclide cisternography findings. Conclusions: The spectrum of clinical symptoms and imaging findings in SIH is highly variable. There- fore the diagnosis of SIH is often delayed. Radio-isotope cisternography is an important additional diagnostic method to detect CSF leaks or pathological kinetics of radio-isotope movement particularly in cases with normal MRI findings.
Ozonized Low Density Lipoprotein (ozLDL) Inhibits NF-κB and IRAK-1–Associated Signaling
Authors: Cappello Christian , Saugel Bernd , Huth Karin C. , Zwergal Andreas , Krautkrämer Martina , Furman Christophe , Rouis Mustapha , Wieser Bianca , Schneider Heike W. , Neumeier Dieter , Brand Korbinian
Published: October 2006

Objective—

Recent studies have provided strong evidence for the presence of ozone in atherosclerotic lesions. In addition, modification of LDL has been suggested to be involved in atherosclerosis. In the present study we wanted to investigate whether LDL exposed to ozone (ozLDL) is able to modulate the NF-κB system, as a paradigm for inflammatory signaling.

Methods and Results—

We showed that activation of NF-κB by lipopolysaccharide (LPS), a prototypic inducer of innate immunity, was reversibly inhibited by ozLDL in monocytic THP-1 cells in a dose-dependent manner, whereas tumor necrosis factor (TNF) signaling was not affected. This was not attributable to a direct ozone effect or solely the presence of lipoprotein, and neither required direct contact to LPS nor was accompanied by a change in LPS binding. Comparable inhibitory effects of ozLDL were observed in human monocyte/macrophages and endothelial cells. The presence of ozLDL led to a decrease in LPS-induced IκΒα proteolysis and a reduction of κB-dependent transcription/target-gene expression. Furthermore, ozLDL markedly lowered stimulus-induced IκΒ kinase (IKK) activity and phosphorylation/proteolysis of interleukin (IL)-1 receptor-associated kinase-1 (IRAK-1). Finally, cholesterol ozonization products were identified as effective ozLDL inhibitory compounds.

Conclusion—

Our study demonstrated that ozLDL inhibited NF-κB and IRAK-1–associated signaling which may impair immune function and promote apoptosis.
Increased Soluble Fas Plasma Levels in Subjects at High Cardiovascular Risk
Authors: Blanco-Colio Luis M. , Martín-Ventura Jose L. , de Teresa Eduardo , Farsang Csaba , Gaw Allan , Gensini GianFranco , Leiter Lawrence A. , Langer Anatoly , Martineau Pierre , Hérnandez Gonzalo , Egido Jesús
Published: October 2006

Objectives—

Increasing evidence indicates that the Fas/Fas ligand interaction is involved in atherogenesis. We sought to analyze soluble Fas (sFas) and soluble Fas ligand (sFasL) concentrations in subjects at high cardiovascular risk and their modulation by atorvastatin treatment.

Methods and Results—

ACTFAST was a 12-week, prospective, multicenter, open-label trial which enrolled subjects (statin-free or statin-treated at baseline) with coronary heart disease (CHD), CHD-equivalent, or 10-year CHD risk >20%. Subjects with LDL-C between 100 to 220 mg/dL (2.6 to 5.7 mmol/L) and triglycerides ≤600 mg/dL (6.8 mmol/L) were assigned to a starting dose of atorvastatin (10 to 80 mg/d) based on LDL-C at screening. Of the 2117 subjects enrolled in ACTFAST, AIM sub-study included the 1078 statin-free patients. At study end, 85% of these subjects reached LDL-C target. Mean sFas levels were increased and sFasL were reduced in subjects at high cardiovascular risk compared with healthy subjects. Atorvastatin reduced sFas in the whole population as well as in patients with metabolic syndrome or diabetes. Minimal changes were observed in sFasL.

Conclusions—

sFas concentrations are increased and sFasL are decreased in subjects at high cardiovascular risk, suggesting that these proteins may be novel markers of vascular injury. Atorvastatin reduces sFas, indicating that short-term treatment with atorvastatin exhibits antiinflammatory effects in these subjects.
Complex I Dysfunction and Tolerance to Nitroglycerin
Authors: Esplugues Juan V. , Rocha Milagros , Nuñez Cristina , Bosca Irene , Ibiza Sales , Herance Jose R. , Ortega Angel , Serrador Juan M. , D’Ocon Pilar , Victor Victor M.
Published: October 2006

Nitroglycerin (GTN) tolerance was induced in vivo (rats) and in vitro (rat and human vessels). Electrochemical detection revealed that the incubation dose of GTN (5×10−6mol/L) did not release NO or modify O2consumption when administered acutely. However, development of tolerance produced a decrease in both mitochondrial O2consumption and theKmfor O2in animal and human vessels and endothelial cells in a noncompetitive action. GTN tolerance has been associated with impairment of GTN biotransformation through inhibition of aldehyde dehydrogenase (ALDH)-2, and with uncoupling of mitochondrial respiration. Feeding rats with mitochondrial-targeted antioxidants (mitoquinone [MQ]) and in vitro coincubation with MQ (10−6mol/L) or glutathione (GSH) ester (10−4mol/L) prevented tolerance and the effects of GTN on mitochondrial respiration and ALDH-2 activity. Biotransformation of GTN requires functionally active mitochondria and induces reactive oxygen species production and oxidative stress within this organelle, as it is inhibited by mitochondrial-targeted antioxidants and is absent in HUVECρ0cells. Experiments analyzing complex I–dependent respiration demonstrate that its inhibition by GTN is prevented by mitochondrial-targeted antioxidants. Furthermore, in presence of succinate (10×10−3mol/L), a complex II electron donor added to bypass complex I–dependent respiration, GTN-treated cells exhibited O2consumption rates similar to those of controls, thus suggesting that complex I was affected by GTN. We propose that, following prolonged treatment with GTN in addition to ALDH-2, complex I is a target for mitochondrially generated reactive oxygen species. Our data also suggest a role for mitochondrial-targeted antioxidants as therapeutic tools in the control of the tolerance that accompanies chronic nitrate use.
Metabolic Risk Factors for Stroke and Transient Ischemic Attacks in Middle-Aged Men
Authors: Wiberg Bernice , Sundström Johan , Árnlöv Johan , Terént Andreas , Vessby Bengt , Zethelius Björn , Lind Lars
Published: October 2006

Background and Purpose—

The impact of lipometabolic and glucometabolic disturbances on stroke incidence remains to be characterized in detail. We investigated relations of a comprehensive panel of baseline lipometabolic and glucometabolic variables to incident fatal and nonfatal stroke or transient ischemic attack (TIA), and stroke subtypes.

Methods—

A community-based prospective study of 2313 middle-aged men invited to a health survey at age 50.

Results—

During a follow-up of up to 32 years, 421 developed stroke or TIA. In Cox proportional hazards analyses adjusting for treatment with cardiovascular drugs at baseline, 1-standard deviation increases in body mass index, systolic and diastolic blood pressures, serum proinsulin, and lipoprotein(a) were associated with 11 to 35% increased risk for subsequent stroke/TIA. Electrocardiographic left ventricular hypertrophy and smoking were also associated with a higher risk for stroke/TIA. Essentially the same variables were related to brain infarction/TIA. Higher proportions of palmitic (16:0), palmitoleic (16:1), and oleic acid (18:1) in cholesterol esters were associated with an increased risk, whereas a higher proportion of linoleic acid (18:2 n-6) was protective against stroke/TIA. Further adjusting all models also for hypertension, diabetes, the metabolic syndrome, serum cholesterol, atrial fibrillation, cardiovascular disease, smoking, and physical activity, essentially the same pattern was observed.

Conclusions—

Indices of an unhealthy dietary fat intake and a high serum lipoprotein (a) level predicted fatal and nonfatal stroke/TIA independently of established risk factors in a community-based sample of middle-aged men followed for 32 years.
Peer Influences on the College-Going Decisions of Low Socioeconomic Status Urban Youth
Authors: Sokatch Andrew
Published: October 2006

The roles that peers play in the decision to go to college are not well understood. Logistic regression is used to explore the role that peers play in the college-going decisions of a sample of low-income urban minority public high school graduates drawn from the National Education Longitudinal Study (NELS:88) database. Friends’ plans are found to be the single best predictor of 4-year college enrollment for these low-income urban minority students, even when controlling for variables traditionally assumed to affect college going. These peer variables are stronger predictors of 4-year college-going behavior for this group than they are for a comparison sample of all U.S. high school graduates. These data are important for the formation of policies to improve all levels of college access programming.
Colice’s Story and the Effects of Generational Loss
Authors: Sherrod Melissa McIntire
Published: October 2006

In 1934, Colice Sayer was forcefully removed from her home and involuntarily committed to a state mental hospital following a legal proceeding she was not allowed to attend. Colice’s husband initiated the complaint against her. Colice remained in the institution for 43 years as a ward of the state of New York. This study examined her life to gain an understanding of how the lives of successive generations were altered. The life history method was used to elicit the stories of the central character and her family. Hermeneutic phenomenology was used to gather and analyze the data. Two themes emerged from the data: learned expectations and retreating behaviors. Learned expectations were family rules taught to successive generations. Retreating behaviors were indirect actions observed or obliquely communicated. The loss of a mother by means of forced, legal separation and the subsequent disintegration of the family can pervasively affect successive generations.
Individuals’ Descriptions of Living With Fibromyalgia
Authors: Cunningham Margaret Mui , Jillings Carol
Published: October 2006

Fibromyalgia (FM) is a chronic pain syndrome with no known etiology, cure, prognosis, or clear diagnostic criteria. This interpretive descriptive study was focused on the experience of living with FM. Using a constant comparative inductive analytic method, the researcher collected and analyzed data from in-depth, semistructured interviews with eight participants. This study’s findings offer insights into the experience of living with and managing FM and identify social, policy, and health care issues that profoundly affect those suffering from it. Participants believe that people with FM would benefit if more health care professionals, as well as family and friends, would validate their condition and provide them with better support. More research could clarify ways in which health care providers may provide more effective interventions, appropriate care, and ongoing support for those affected with FM.
Parental Experiences: Care of Children With High and Intermediate Imperforate Anus
Authors: Öjmyr-Joelsson Maria , Nisell Margret , Frenckner Björn , Rydelius Per-Anders , Christensson Kyllike
Published: October 2006

In this study parental experiences of care of children with high and intermediate imperforate anus were evaluated. A group of 45 parents of children with high and intermediate imperforate anus and two control groups participated. Data collection with individual questionnaires concerning the child's hospital care, information to the parent and the child, and involvement in the care of the child were performed. Parents of children with imperforate anus reported being less satisfied with the care of their child, and they were less content with information about their child's treatment compared with the control groups. The parents had been extremely involved in the follow-up treatment. Constipation and fecal incontinence are common and involve suffering for the children and their parents. Parents have to be motivated and supportive and have a great deal of patience to be able to put up with caring for these children, and it seems as if health care professionals have underestimated their problems.
Selective abrogation of Th1 response by STA-5326, a potent IL-12/IL-23 inhibitor
Authors: Wada Yumiko , Lu Rongzhen , Zhou Dan , Chu John , Przewloka Teresa , Zhang Shijie , Li Long , Wu Yaming , Qin June , Balasubramanyam Vishwasenani , Barsoum James , Ono Mitsunori
Published: October 2006

The interleukin-12 (IL-12) cytokine induces the differentiation of naive T cells to the T helper cell type 1 (Th1) phenotype and is integral to the pathogenesis of Th1-mediated immunologic disorders. A more recently discovered IL-12 family member, IL-23, shares the p40 protein subunit with IL-12 and plays a critical role in the generation of effector memory T cells and IL-17–producing T cells. We introduce a novel compound, STA-5326, that down-regulates both IL-12 p35 and IL-12/IL-23 p40 at the transcriptional level, and inhibits the production of both IL-12 and IL-23 cytokines. Oral administration of STA-5326 led to a suppression of the Th1 but not Th2 immune response in mice. In vivo studies using a CD4+CD45Rbhigh T-cell transfer severe combined immunodeficiency (SCID) mouse inflammatory bowel disease model demonstrated that oral administration of STA-5326 markedly reduced inflammatory histopathologic changes in the colon. A striking decrease in interferon-γ (IFN-γ) production was observed in ex vivo culture of lamina propria cells harvested from animals treated with STA-5326, indicating a down-regulation of the Th1 response by STA-5326. These results suggest that STA-5326 has potential for use in the treatment of Th1-related autoimmune or immunologic disorders. STA-5326 currently is being evaluated in phase 2 clinical trials in patients with Crohn disease and rheumatoid arthritis.
Impaired ribosome biogenesis in Diamond-Blackfan anemia
Authors: Choesmel Valérie , Bacqueville Daniel , Rouquette Jacques , Noaillac-Depeyre Jacqueline , Fribourg Sébastien , Crétien Aurore , Leblanc Thierry , Tchernia Gil , Da Costa Lydie , Gleizes Pierre-Emmanuel
Published: October 2006

The gene encoding the ribosomal protein S19 (RPS19) is frequently mutated in Diamond-Blackfan anemia (DBA), a congenital erythroblastopenia. The consequence of these mutations on the onset of the disease remains obscure. Here, we show that RPS19 plays an essential role in biogenesis of the 40S small ribosomal subunit in human cells. Knockdown of RPS19 expression by siRNAs impairs 18S rRNA synthesis and formation of 40S subunits and induces apoptosis in HeLa cells. Pre-rRNA processing is altered, which leads to an arrest in the maturation of precursors to the 18S rRNA. Under these conditions, pre-40S particles are not exported to the cytoplasm and accumulate in the nucleoplasm of the cells in perinuclear dots. Consistently, we find that ribosome biogenesis and nucleolar organization is altered in skin fibroblasts from DBA patients bearing mutations in the RPS19 gene. In addition, maturation of the 18S rRNA is also perturbed in cells from a patient bearing no RPS19-related mutation. These results support the hypothesis that DBA is directly related to a defect in ribosome biogenesis and indicate that yet to be discovered DBA-related genes may be involved in the synthesis of the ribosomal subunits.