bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathological classification of anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis
Authors: Bajema I M 
Published: March 2011

Summary
What drives human beings to classify? It seems as if it is within our nature to do so. Clinical classification systems for the systemic vasculitides were composed a long time ago, and they are constantly being revised and altered. The histopathological features of many diseases are so diverse that classification is called for. The histopathological classification for anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis was the culmination of results produced from a number of clinicopathological studies conducted within the European Vasculitis Study Group (EUVAS). The classification scheme has four general categories, named focal, crescentic, sclerotic and mixed. The first three categories are based on the predominance of normal glomeruli, glomeruli with cellular crescents and globally sclerotic glomeruli. The mixed category represents a heterogeneous phenotype of biopsies in which none of the aforementioned features is dominant. Results from a validation study incorporating 100 patients with at least 1-year follow-up showed that the phenotypical order of the four classes corresponded to the severity of renal function impairment. The new histopathological classification for ANCA-associated glomerulonephritis provides a logical structure for the categorization of patients into four subgroups defined according to glomerular features. This classification will be of use for future studies, such as clinical trials.
Epigenetics and complementary proteins
Authors: Ciavatta D , Falk R J 
Published: March 2011

Summary
Although studies on the immunopathogenesis of anti-neutrophil cytoplasm antibody (ANCA) vasculitis have been directed at understanding the autoantibody, there is growing evidence that points to the importance of ANCA autoantigen genes and their regulation. Transcriptional analysis indicates that ANCA autoantigen genes are active in mature neutrophils of ANCA vasculitis patients compared to healthy controls. The unusual transcriptional state of neutrophils from ANCA vasculitis patients appears to be a consequence of failed or disrupted epigenetic silencing. Defective epigenetic silencing could have global effects, by altering the transcriptional and phenotypic state of neutrophils, or local effects by permitting transcription of autoantigen genes from both strands resulting in anti-sense transcripts. Although the role of anti-sense transcripts is currently unknown, there are two intriguing possibilities. Anti-sense transcripts could function (as described for other genes) in transcriptional silencing of autoantigen genes, which takes place in normal neutrophil progenitors. In the setting of failed epigenetic silencing, the fate of anti-sense transcripts may be pathological and serve as a template for production of complementary autoantigens. The observation that ANCA vasculitis patients have anti-sense transcripts and antibodies to complementary proteins is consistent with a role of anti-sense transcripts in complementary protein production. A better understanding of epigenetic silencing and complementary proteins in ANCA vasculitis may unlock the underlying pathology of this condition.
Pathogenesis of anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis
Authors: Savage C O S 
Published: March 2011

Summary
Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis is an autoimmune disease in which the contributions of genetic, epigenetic and environmental factors to aetiology and pathogenesis are being unravelled. The ANCA immunoglobulin G targeting proteinase 3 and myeloperoxidase affects several neutrophil functions, usually to augment or dysregulate these, promoting a proinflammatory phenotype whereby neutrophils have enhanced capabilities of causing collateral damage to endothelial and other cells. In addition, B cells are intimately involved in pathogenesis as anti-B cell therapies are highly effective, but the manner of this involvement still needs to be delineated. Similarly, the T cell compartment is disturbed in ANCA vasculitis and numerous alterations in T cell subsets have been described, but recognition of a novel CD8+ T cell transcription signature which can predict likelihood of relapse in ANCA vasculitis indicates that more needs to be learnt about the influence of T cells in the disease process. Finally, the role of the alternative complement pathway and the potential therapeutic value of its neutralization is under active investigation after compelling studies in murine models have demonstrated that C5 and factor-B knock-out mice are protected.
Peak and trough growth hormone (GH) concentrations influence growth and serum insulin like growth factor‐1 (IGF‐1) concentrations in short children
Authors: Achermann J. C. , Brook C. G. D. , Robinson I. C. A. F. , Matthews D. R. , Hindmarsh P. C. 
Published: March 2011

SummaryOBJECTIVE Growth hormone (GH) is secreted in a pulsatile fashion promoting growth and a number of diverse metabolic actions. The precise components of the pulsatile signal involved in growth regulation are unclear.DESIGN A retrospective analysis of 24 h serum GH concentration profiles to evaluate the relative contribution of peak and trough serum GH concentrations to growth regulation, GH response to insulin induced hypoglycaemia (ITT) and serum insulin like growth factor‐1 (IGF‐1) concentration.PATIENTS Fifty short prepubertal children (age 5·2–11·9 years).MEASUREMENT Analysis of the hormone profile by a concentration distribution method that determines the concentration at or below which the serum GH concentrations in the 24 hour profile spend a percentage of the total time. The method generates an estimate of the observed concentrations (OC) below which 95 % and 5 % of the values in the time series lie: OC 95 (peaks) and OC5 (troughs).RESULTS Twenty six of the children were growing at a normal rate for short children with a height velocity standard deviation score (HVSDS) between +0·4 and −0·8 whereas twenty four were growing more slowly (HVSDS between −0·9 to −3·9). The former group had a mean peak GH response to ITT of 27·3 (11·1) mU/l whereas the latter had a mean value of 8·7 (6·5) mU/l. There was no relationship between (peak and trough GH concentration) and the age of the individual or body mass index. Peak GH levels were positively related to HVSDS and serum IGF‐1 values (r = 0·44; P= 0·002 and r = 0·53; P= 0·002, respectively). GH trough levels were inversely related to these measurements (r = 0·29; P= 0·05; and r = 0·46; P= 0·002, respectively). Further analysis showed that individuals with the slowest growth rates and lowest IGF‐1 concentrations had the lowest peak and highest trough GH concentrations (anova F = 6·0; P= 0·002). Similarly, the peak GH response to ITT was lowest in those individuals with high troughs and low peaks (anova F = 9·99; P < 0·001).CONCLUSIONS These results suggest that the peak values of a GH concentration profile influence growth rate and the IGF‐1 axis whereas elevated trough values have the greatest influence on growth rate and IGF‐1 values when GH peaks are low.
ICE1 Ser403 is necessary for protein stabilization and regulation of cold signaling and tolerance
Authors: Miura Kenji , Ohta Masaru , Nakazawa Machiko , Ono Michiyuki , Hasegawa Paul M. 
Published: March 2011

SummaryICE1, a MYC‐type transcription factor, has an important role in the induction of CBF3/DREB1A for regulation of cold signaling and tolerance. Here we reveal that serine 403 of ICE1 is involved in regulating the transactivation and stability of the ICE1 protein. Substitution of serine 403 by alanine enhanced the transactivational activity of ICE1 in Arabidopsis protoplasts. Over‐expression of ICE1(S403A) conferred more freezing tolerance than ICE1(WT) in Arabidopsis, and the expression of cold‐regulated genes such as CBF3/DREB1A, COR47 and KIN1 was enhanced in plants over‐expressing ICE1(S403A). Furthermore, the ICE1(S403A) protein level was not changed after cold treatment, whereas the ICE1(WT) protein level was reduced. Interestingly, polyubiquitylation of the ICE1(S403A) protein in vivo was apparently blocked. These results demonstrate that serine 403 of ICE1 has roles in both transactivation and cold‐induced degradation of ICE1 via the ubiquitin/26S proteasome pathway, suggesting that serine 403 is a key residue for the attenuation of cold‐stress responses by HOS1‐mediated degradation of ICE1.
Married to M. tuberculosis: risk of infection and disease in spouses of smear‐positive tuberculosis patients
Authors: Crampin A. , Kasimba S. , Mwaungulu N. J. , Dacombe R. , Floyd S. , Glynn J. R. , Fine P. E. M. 
Published: March 2011

SummaryObjectives  To quantify the risk of infection and disease in spouses of tuberculosis patients and the extent to which intervention could reduce the risk in this highly exposed group.Methods  We compared HIV prevalence, TB prevalence and incidence and tuberculin skin test (TST) results in spouses of TB patients and community controls. HIV‐positive spouses were offered isoniazid preventive therapy (IPT), and TST was repeated at 6, 12 and 24 months.Results  We recruited 148 spouses of smear‐positive patients ascertained prospectively and 3% had active TB. We identified 203 spouses of previously diagnosed smear‐positive patients, 11 had already had TB, and the rate of TB was 2.4 per 100 person years(py) over 2 years (95% CI 1.15–5.09). 116 were found alive and recruited. HIV prevalence was 37% and 39% in the prospective and retrospective spouse groups and 17% in controls. TST was ≥10 mm in 80% of HIV negative and in 57% of HIV‐positive spouses ascertained retrospectively; 74% HIV negative and 62% HIV‐positive spouses ascertained prospectively, and 48% HIV negative and 26% HIV‐positive community controls. Of 54 HIV‐positive spouses, 18 completed 6‐month IPT. At 2 year follow‐up, 87% of surviving spouses had TST ≥10 mm and the rate of TB was 1.1 per 100 py (95% CI 0.34–3.29).Conclusions  Spouses are a high‐risk group who should be screened for HIV and active TB. TST prevalence was already high by the time the spouses were approached but further infections were seen to occur. Uptake and adherence to IPT was disappointing, lessening the impact of short‐duration therapy.
Genotyping of polymorphic marker (MSP3α and MSP3β) genes of Plasmodium vivax field isolates from malaria endemic of Thailand
Authors: Rungsihirunrat Kanchana , Chaijaroenkul Wanna , Siripoon Napapoon , Seugorn Aree , Na‐Bangchang Kesara 
Published: March 2011

SummaryTwo polymorphic marker genes, merozoite surface protein 3α (PvMSP3α) and merozoite surface protein 3β (PvMSP3β), from 100 Plasmodium vivax field isolates, were investigated using polymerase chain reaction and restriction fragment length polymorphism (PCR/RFLP). Genotyping of PvMSP3α and PvMSP3β revealed marked polymorphisms in length and sequence. Three major types of PvMSP3α (Type A, B and C) and two major types of PvMSP3β (Type A and B) were detected based on the length of PCR products. Fourteen alleles of both genes with difference frequencies were distinguished by restriction fragment length polymorphism, and these results strongly support that P. vivax isolates in Thailand are markedly diverse. PvMSP3α and PvMSP3β are reliable polymorphic markers for population genetic analysis of P. vivax, and PCR/RFLP provides a powerful method for genotyping and identification of mixed parasite infections without requirement of gene sequencing.
Health care‐seeking behaviour and diagnostic delays for Human African Trypanosomiasis in the Democratic Republic of the Congo
Authors: Hasker E. , Lumbala C. , Mbo F. , Mpanya A. , Kande V. , Lutumba P. , Boelaert M. 
Published: March 2011

SummaryObjective  About half of the patients with Human African trypanosomiasis (HAT) reported in the Democratic Republic of the Congo (DRC) are currently detected by fixed health facilities and not by mobile teams. Given the recent policy to integrate HAT control into general health services, we studied health seeking behaviour in these spontaneously presenting patients.Methods  We took a random sample from all patients diagnosed with a first‐time HAT episode through passive case finding between 1 October 2008 and 30 September 2009 in the two most endemic provinces of the DRC. Patients were approached at their homes for a structured interview. We documented patient delay (i.e. time between onset of symptoms and contacting a health centre) and health system delay (i.e. time between first contact and correct diagnosis of HAT).Results  Median patient delay was 4 months (IQR 1–10 months, n = 66); median health system delay was 3 months (IQR 0.5–11 months). Those first presenting to public health centres had a median systems delay of 7 months (IQR 2–14 months, n = 23). On median, patients were diagnosed upon the forth visit to a health facility (IQR 3rd–7th visit).Conclusions  Substantial patient as well as health system delays are incurred in HAT cases detected passively. Public health centres are performing poorly in the diagnostic work‐up for HAT, mainly because HAT is a relatively rare disease with few and non‐specific early symptoms. Integration of HAT diagnosis and treatment into general health services requires strong technical support and well‐organized supervision and referral mechanisms.
Asbestos use and asbestos‐related diseases in Asia: Past, present and future
Authors: LE GIANG VINH , TAKAHASHI KEN , PARK EUN‐KEE , DELGERMAA VANYA , OAK CHULHO , QURESHI AHMAD MUNIR , ALJUNID SYED MOHAMED 
Published: March 2011

ABSTRACTBackground and objective:  Although there are growing concerns about the global epidemic of asbestos‐related diseases (ARD), the current status of asbestos use and ARD in Asia is elusive. We conducted a descriptive analysis of available data on asbestos use and ARD to characterize the current situation in Asia.Methods:  We used descriptive indicators of per capita asbestos use (kilograms per capita per year) and age‐adjusted mortality rates (AAMR, persons per million population per year) by country and for the region, with reference to the world.Results:  The proportion of global asbestos use attributed to Asia has been steadily increasing over the years from 14% (1920–1970) to 33% (1971–2000) to 64% (2001–2007). This increase has been reflected in the absolute level of per capita use across a wide range of countries. In contrast, 12 882 ARD deaths have been recorded cumulatively in Asia, which is equivalent to only 13% of the cumulative number of ARD deaths in the world during the same period. The highest AAMR were recorded in Cyprus (4.8), Israel (3.7) and Japan (3.3), all of which have banned asbestos use.Conclusions:  There is a paucity of information concerning the current situation of ARD in Asia. The marked increase in asbestos use in Asia since 1970, however, is likely to trigger a surge of ARD in the immediate decades ahead.
Ketamine for perioperative pain management in children: a meta‐analysis of published studies
Authors: Dahmani Souhayl , Michelet Daphné , Abback Paer‐Selim , Wood Chantal , Brasher Christopher , Nivoche Yves , Mantz Jean 
Published: March 2011

SummaryIntroduction:  Balanced analgesia, using both opioid and nonopioids agents, has become the standard care for postoperative pain management. Ketamine, a compound with analgesic and antihyperalgesic properties, has been shown to decrease postoperative pain and opioid requirements in adults. The goal of the present meta‐analysis was to investigate postoperative analgesic properties of ketamine in pediatric patients.Material and methods:  A comprehensive literature search was conducted to identify clinical trials that used ketamine as a perioperative analgesic compound in children and infants. Outcomes measured were postoperative analgesic consumption, pain intensity and duration of sensory block (when ketamine was used by caudal route) during the postoperative care unit (PACU) stay and the early postoperative period (6–24 h after leaving the operative room). The data from each trial were combined to calculate the pooled odds ratios or standard mean differences and their 95% confidence intervals.Results:  Thirty‐five randomized, blinded controlled studies were retrieved from the literature. Systemic ketamine was effective in decreasing PACU pain intensity and analgesic requirement but failed to influence early (6–24 h) pain intensity and analgesic requirement. Ketamine administered locally during tonsillectomy, decreased PACU and early (6–24 h) pain intensity and PACU analgesic requirements. Used as an adjuvant for caudal analgesia, ketamine increased the duration of sensory block and PACU analgesic requirement without impacting PACU pain intensity. Ketamine failed to exhibit a postoperative opioid‐sparing effect.Conclusions:  This meta‐analysis found that administration of ketamine was associated with decreased PACU postoperative pain intensity and nonopioid analgesic requirement. However, ketamine failed to exhibit a postoperative opioid‐sparing effect.
Quantitative pharmacological analysis of antagonist binding kinetics at CRF1 receptors in vitro and in vivo
Authors: Ramsey Simeon J , Attkins Neil J , Fish Rebecca , van der Graaf Piet H 
Published: March 2011

BACKGROUND AND PURPOSE A series of novel non‐peptide corticotropin releasing factor type‐1 receptor (CRF1) antagonists were found to display varying degrees of insurmountable and non‐competitive behaviour in functional in vitro assays. We describe how we attempted to relate this behaviour to ligand receptor‐binding kinetics in a quantitative manner and how this resulted in the development and implementation of an efficient pharmacological screening method based on principles described by Motulsky and Mahan.EXPERIMENTAL APPROACH A non‐equilibrium binding kinetic assay was developed to determine the receptor binding kinetics of non‐peptide CRF1 antagonists. Nonlinear, mixed‐effects modelling was used to obtain estimates of the compounds association and dissociation rates. We present an integrated pharmacokinetic–pharmacodynamic (PKPD) approach, whereby the time course of in vivo CRF1 receptor binding of novel compounds can be predicted on the basis of in vitro assays.KEY RESULTS The non‐competitive antagonist behaviour appeared to be correlated to the CRF1 receptor off‐rate kinetics. The integrated PKPD model suggested that, at least in a qualitative manner, the in vitro assay can be used to triage and select compounds for further in vivo investigations.CONCLUSIONS AND IMPLICATIONS This study provides evidence for a link between ligand offset kinetics and insurmountable/non‐competitive antagonism at the CRF1 receptor. The exact molecular pharmacological nature of this association remains to be determined. In addition, we have developed a quantitative framework to study and integrate in vitro and in vivo receptor binding kinetic behaviour of CRF1 receptor antagonists in an efficient manner in a drug discovery setting.
Corporate Governance and Efficiency: Evidence From U.S. Property–Liability Insurance Industry
Authors: Huang Li‐Ying , Lai Gene C. , McNamara Michael , Wang Jennifer 
Published: March 2011

AbstractThis study examines the relation between corporate governance and the efficiency of the U.S. property–liability insurance industry during the period from 2000 to 2007. We find a significant relation between efficiency and corporate governance (board size, proportion of independent directors on the audit committee, proportion of financial experts on the audit committee, director tenure, proportion of block shareholding, average number of directorships, proportion of insiders on the board, and auditor dependence). We also find property–liability insurers have complied with the Sarbanes‐Oxley Act (SOX) to a large extent. Although SOX achieved the goal of greater auditor independence and might have prevented Enron‐like scandals, it had some unexpected effects. For example, insurers became less efficient when they had more independent auditors because the insurers were unable to recoup the benefits of auditor independence.
Niches of temperate tree species converge towards nutrient‐richer conditions over ontogeny
Authors: Bertrand Romain , Gégout Jean‐Claude , Bontemps Jean‐Daniel 
Published: March 2011

Niche changes during a species’ lifespan are known as ontogenetic niche shifts. These shifts reflect changes in resource availability, requirements, organisms’ foraging ability and/or size‐dependent biotic interactions. In the plant kingdom, however, this issue remains poorly covered.We investigated nutritional niche shifts over the ontogeny of 23 temperate tree species (among nine phylogenetic families) by a synchronic approach. We used 1963 temporary phytoecological surveys conducted throughout metropolitan French forests. The realised niches of three life‐history stages (seedling: <0.5 m; sapling: >0.5 m and < 8 m; tree: >8 m) in each tree species were modelled on the basis of presence/absence data and the main factors of species distribution (energy, water and nutritional resources). We computed the nutritional optima and amplitudes by bootstrapping partial response curves for the C:N ratio and base saturation rate. We assessed changes in these niche parameters over ontogeny and also evaluated the relative importance of ontogenetic shifts in the differentiation of nutritional niche among the selected tree species.The tree stage was found to occur mainly at higher nutrient availability than the seedling (+16.3% on the nutritional gradient) or sapling (+11.1%) stages. In addition, nutritional niches of tree species exhibited, successively, a niche enlargement in eutrophic conditions and a niche restriction in oligotrophic conditions during growth. These global nutritional niche shifts observed over the species’ lifespan contributed moderately but significantly to the niche separation in temperate tree communities (up to 4.5%).We interpreted niche shifts as a response to an increase in nutritional requirements over ontogeny, leading to an intra‐specific selection where individuals established in eutrophic soils have the maximal fitness. Biotic interactions and temporal changes in the environment may secondarily enhance or counteract the process. The importance of ontogenetic niche shifts requires consideration in the study of species autecology and plant community organisation.