bluuebunny/crossref_metadata_2025_split huggingface dataset:
Additional human β2‐microglobulin curbs HLA–B27 misfolding and promotes arthritis and spondylitis without colitis in male HLA–B27–transgenic rats
Authors: Tran Tri M. , Dorris Martha L. , Satumtira Nimman , Richardson James A. , Hammer Robert E. , Shang Jie , Taurog Joel D. 
Published: March 2006

AbstractObjectiveAnkylosing spondylitis and related spondylarthritides are associated with HLA–B27, and also with intestinal inflammation, by unknown mechanisms. The folded HLA–B27 molecule is a trimer of heavy chain, β2‐microglobulin (β2m), and short peptide. However, B27 heavy chain has an unusual propensity to misfold and trigger the unfolded protein response (UPR). This study was initiated to test the hypothesis that B27 misfolding plays a role in the pathogenesis of spondylarthritis.MethodsRats with high transgene copy numbers of HLA–B27 heavy chain together with human β2m (Huβ2m) spontaneously develop colitis, peripheral arthritis, and occasional spondylitis, and those with lower transgene copy numbers remain healthy. We crossed disease‐prone and healthy HLA–B27/Huβ2m–transgenic rat lines with a healthy line, 283‐2, carrying only the Huβ2m transgene. HLA–B27 assembly was assessed by pulse‐chase analysis of B27 molecules, and UPR triggering was assessed by measuring BiP/Grp78 messenger RNA (mRNA) in splenic concanavalin A blasts. Surface expression of B27 and Huβ2m was determined by flow cytometry. Disease manifestations were identified by clinical observation, histology, and measurement of cytokine mRNA.ResultsThe extra Huβ2m from the 283‐2 line significantly reduced B27 misfolding and UPR triggering. Unexpectedly, however, F1 male offspring of the healthy 21‐3 line crossed with the 283‐2 line showed a high prevalence, severity, and duration of arthritis and spondylitis, in the absence of colitis. The arthropathy showed many features characteristic of human spondylarthritis.ConclusionThese results suggest that B27 misfolding is associated with intestinal inflammation, but that neither B27 misfolding nor intestinal inflammation is critical to the development of B27‐associated arthropathy.
Synovial membrane cytokine expression is predictive of joint damage progression in rheumatoid arthritis: A two‐year prospective study (the DAMAGE study cohort)
Authors: Kirkham Bruce W. , Lassere Marissa N. , Edmonds John P. , Juhasz Katherine M. , Bird Paul A. , Lee C. Soon , Shnier Ron , Portek Ian J. 
Published: March 2006

AbstractObjectiveThe primary aim of this prospective 2‐year study was to explain the wide variability in joint damage progression in patients with rheumatoid arthritis (RA) from measures of pathologic changes in the synovial membrane.MethodsPatients underwent clinical measurements and joint damage assessments by magnetic resonance imaging (MRI) and radiography at enrollment and at year 2. Synovial membrane was obtained by knee biopsy and assessed histologically by hematoxylin and eosin staining. Interleukin‐1β (IL‐1β), IL‐10, IL‐16, IL‐17, RANKL, tumor necrosis factor α (TNFα), and interferon‐γ (IFNγ) messenger RNA (mRNA) expression was determined by quantitative reverse transcription–polymerase chain reaction. The relationship of synovial measurements to joint damage progression was determined by multivariate analysis.ResultsSixty patients were enrolled. Histologic features had no relationship to damage progression. Multivariate analysis by several different methods consistently demonstrated that synovial membrane mRNA levels of IL‐1β, TNFα, IL‐17, and IL‐10 were predictive of damage progression. IL‐17 was synergistic with TNFα. TNFα and IL‐17 effects were most pronounced with shorter disease duration, and IL‐1β effects were most pronounced with longer disease duration. IFNγ was protective. These factors explained 57% of the MRI joint damage progression over 2 years.ConclusionWe have demonstrated for the first time in a prospective study that synovial membrane cytokine mRNA expression is predictive of joint damage progression in RA. The findings for IL‐1β and TNFα are consistent with results of previous clinical research, but the protective role of IFNγ, the differing effects of disease duration, and IL‐17–cytokine interactions had only been demonstrated previously by animal and in vitro research. These findings explain some of the variability of joint damage in RA and identify new targets for therapy.
Mesenchymal multipotency of adult human periosteal cells demonstrated by single‐cell lineage analysis
Authors: De Bari Cosimo , Dell'Accio Francesco , Vanlauwe Johan , Eyckmans Jeroen , Khan Ilyas M. , Archer Charles W. , Jones Elena A. , McGonagle Dennis , Mitsiadis Thimios A. , Pitzalis Costantino , Luyten Frank P. 
Published: March 2006

AbstractObjectiveTo investigate whether periosteal cells from adult humans have features of multipotent mesenchymal stem cells (MSCs) at the single‐cell level.MethodsCell populations were enzymatically released from the periosteum of the proximal tibia obtained from adult human donors and then expanded in monolayer. Single‐cell–derived clonal populations were obtained by limiting dilution. Culture‐expanded periosteal cell populations were tested for their growth potential and for expression of conventional markers of MSCs and were subjected to in vitro assays to investigate their multilineage potential. To assess their multipotency in vivo, periosteal cells were injected into a regenerating mouse tibialis anterior muscle for skeletal myogenesis or were either seeded into an osteoinductive matrix and implanted subcutaneously into nude mice for osteogenesis or implanted in a joint surface defect under a periosteal flap into goats for chondrogenesis. Cell phenotypes were analyzed by histochemistry and immunohistochemistry and by reverse transcription–polymerase chain reaction for the expression of lineage‐related marker genes.ResultsRegardless of donor age, periosteal cells were clonogenic and could be expanded extensively in monolayer, maintaining linear growth curves over at least 30 population doublings. They displayed long telomeres and expressed markers of MSCs. Under specific conditions, both parental and single‐cell–derived clonal cell populations differentiated to the chondrocyte, osteoblast, adipocyte, and skeletal myocyte lineages in vitro and in vivo.ConclusionOur study demonstrates that, regardless of donor age, the adult human periosteum contains cells that, upon enzymatic release and culture expansion, are multipotent MSCs at the single‐cell level.
Regulatory role of heme oxygenase 1 in inflammation of rheumatoid arthritis
Authors: Kobayashi Hideo , Takeno Mitsuhiro , Saito Tomoyuki , Takeda Yukiko , Kirino Yohei , Noyori Koji , Hayashi Takeshi , Ueda Atsuhisa , Ishigatsubo Yoshiaki 
Published: March 2006

AbstractObjectiveTo examine the expression and pathogenetic roles of heme oxygenase 1 (HO‐1), an inducible heme‐degrading enzyme with antiinflammatory properties, in rheumatoid arthritis (RA).MethodsHO‐1 expression in synovial tissue from patients with RA, patients with osteoarthritis, and patients with noninflammatory joint diseases was determined by immunoblotting and immunohistochemistry. Effects of various agents, such as hemin (a chemical inducer of HO‐1), small interfering RNA (siRNA) specific for HO‐1, HO‐1 expression vector, and antirheumatic agents, on HO‐1 expression in RA synovial cell lines were analyzed by real‐time reverse transcription–polymerase chain reaction (PCR) and immunoblotting. Cytokine synthesis was evaluated by real‐time PCR and enzyme‐linked immunosorbent assay.ResultsHO‐1 was expressed more abundantly in the lesions of synovial tissue from patients with RA than in those from the other patient groups. Hemin, auranofin, and HO‐1 expression vector induced HO‐1 and reduced expression of tumor necrosis factor α (TNFα) messenger RNA, lipopolysaccharide (LPS)–induced secretion of interleukin‐6 (IL‐6) and IL‐8, and expression of cyclooxygenase 2 in the synovial cell lines. Treatment with HO‐1–specific siRNA augmented the synthesis of TNFα, IL‐6, and IL‐8 and canceled the suppressive effects of auranofin on TNFα secretion. When hemoglobin, as a scavenger of carbon monoxide, was added to auranofin‐treated synovial cell lines, LPS‐dependent production of IL‐6 and IL‐8 was increased.ConclusionOur data demonstrate that HO‐1 is expressed in RA synovial tissues and plays a regulatory role in the development of inflammation. The pharmacologic effects of auranofin depend, in part, on the levels of HO‐1, suggesting that HO‐1 induction is a novel therapeutic strategy for RA.
Primary central nervous system vasculitis in children
Authors: Benseler Susanne M. , Silverman Earl , Aviv Richard I. , Schneider Rayfel , Armstrong Derek , Tyrrell Pascal N. , deVeber Gabrielle 
Published: March 2006

AbstractObjectivePrimary angiitis of the central nervous system (PACNS) is a severe and ill‐defined neurologic disease. The goal of this study was to characterize the presenting features, treatment, and neurologic outcome of PACNS in children (cPACNS) and to define the predictors of disease progression in order to identify high‐risk patients with cPACNS.MethodsThe cohort comprised consecutive patients diagnosed as having cPACNS based on clinical and vascular imaging findings, including identification of arterial stenosis on conventional angiography or magnetic resonance (MR) angiography. Disease progression was defined angiographically at >3 months after initial angiography. Clinical data obtained in prospectively collected standardized assessments and results of laboratory tests, including detection of cerebrospinal fluid abnormalities, were noted, and neuroimaging studies were reanalyzed. Predictors of progression were identified and tested in multivariate regression models.ResultsSixty‐two consecutive patients with cPACNS (38 male, 24 female, median age 7.2 years) were included. Two distinct subgroups were identified, those with progressive disease and those with nonprogressive disease. Progressive cPACNS was found in 20 of 62 children and was predicted by a clinical presentation of neurocognitive dysfunction, multifocal parenchymal lesions on MR imaging, and evidence of distal stenoses on angiography.ConclusionThe spectrum of PACNS in children includes both progressive and nonprogressive forms. Characteristic features at diagnosis can be used to predict later progression, to identify a distinct high‐risk cPACNS cohort, and to help guide selection of patients for immunosuppressive therapy.
Potent induction of chondrocytic differentiation of human adipose‐derived adult stem cells by bone morphogenetic protein 6
Authors: Estes Bradley T. , Wu Arthur W. , Guilak Farshid 
Published: March 2006

AbstractObjectiveRecent studies have identified an abundant source of multipotent progenitor cells in subcutaneous human adipose tissue, termed human adipose‐derived adult stem cells (ADAS cells). In response to specific media formulations, including transforming growth factor β1 (TGFβ1), these cells exhibit significant ability to differentiate into a chondrocyte‐like phenotype, expressing cartilage‐specific genes and proteins such as aggrecan and type II collagen. However, the influence of other growth factors on the chondrogenic differentiation of ADAS cells is not fully understood. This study was undertaken to investigate the effects of TGFβ1, TGFβ3, insulin‐like growth factor 1, bone morphogenetic protein 6 (BMP‐6), and dexamethasone, in various combinations, on the chondrogenic potential of ADAS cells in alginate beads.MethodsThe chondrogenic response of alginate‐encapsulated ADAS cells was measured by quantitative polymerase chain reaction, 3H‐proline and 35S‐sulfate incorporation, and immunolabeling for specific extracellular matrix components.ResultsSignificant differences in chondrogenesis were observed under the different culture conditions for all outcomes measured. Most notably, BMP‐6 up‐regulated AGC1 and COL2A1 expression by an average of 205‐fold and 38‐fold, respectively, over day‐0 controls, while down‐regulating COL10A1 expression by ∼2‐fold.ConclusionThese findings suggest that BMP‐6 is a potent inducer of chondrogenesis in ADAS cells, in contrast to mesenchymal stem cells, which exhibit increased expression of type X collagen and a hypertrophic phenotype in response to BMP‐6. Combinations of growth factors containing BMP‐6 may provide a novel means of regulating the differentiation of ADAS cells for applications in the tissue‐engineered repair or regeneration of articular cartilage.
Fat intake and the risk of gastroschisis
Authors: Siega‐Riz Anna Maria , Olshan Andy F. , Werler Martha M. , Moore Cynthia 
Published: March 2006

AbstractBACKGROUNDYoung age has been associated with an increased risk of gastroschisis. It has been suggested that the pathogenesis of gastroschisis may be related to vascular disruption. Nutrients that may be associated with vasoconstriction include dietary fat and its subtypes. The objective of this study was to examine the association between dietary fats and gastroschisis and whether maternal age modified this association.METHODSData came from the National Birth Defects Prevention Study (NBDPS), which included 304 isolated gastroschisis cases and 3313 controls. Dietary intake in the year prior to conception was ascertained using a food frequency questionnaire, and included total, saturated, monosaturated, and polyunsaturated fat and cholesterol. Unconditional logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for confounders. Age and smoking were tested as effect modifiers.RESULTSHigher mean intakes of total energy, total fat, and cholesterol as well as the subtypes of fats were found for gastroschisis cases compared to controls. Cases were more likely to be in the middle (adjusted OR [AOR], 1.3; 95% CI, 0.9–1.9) and highest (AOR, 1.2; 95% CI, 0.8–1.7) tertile of total fat intake compared to controls. This pattern was also true for saturated fat intake. No association was found for mono or polyunsaturated fat. Cases were less likely to be in the middle (AOR, 0.6; 95% CI, 0.4–0.9) and highest (AOR, 0.8; 95% CI, 0.6–1.2) tertiles for cholesterol. There was no evidence of effect modification.CONCLUSIONSA possible weak effect of increased risk of gastroschisis associated with higher intakes of total fat or saturated fat was found in the NBDPS; however, this did not help to explain why younger aged women are at greater risk of having an infant with this type of birth defect. Birth Defects Research (Part A), 2006. © 2006 Wiley‐Liss, Inc.
Quantitative fluorescence spectra and quantum yield map of synthetic pheomelanin
Authors: Nighswander‐Rempel S. P. 
Published: March 2006

AbstractSpectroscopic studies of pheomelanin and its constituents have been sparse. These data present what is by far the most complete description of the fluorescence characteristics of synthetic pheomelanin. Emission spectra between 260 and 600 nm were acquired for excitation wavelengths between 250 and 500 nm at 1‐nm intervals. A quantum yield map is also presented, correcting the fluorescence intensities for differences in species concentration and molar absorptivity. These fluorescence features exhibit interesting similarities and differences to eumelanin, and these data are interpreted with respect to possible chemical structures. Overall, these data suggest that pheomelanin oligomers may be more tightly coupled than those of eumelanin. Finally, the quantum yield is shown to be on the order of 10−4 and exhibit a complex dependence on excitation energy, varying by a factor of 4 across the energies employed here. © 2006 Wiley Periodicals, Inc. Biopolymers 82: 631–637, 2006This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
A survey of female patients in high security psychiatric care in Scotland
Authors: Thomson Lindsay D.G. , Bogue John P. , Humphreys Martin S. , Johnstone Eve C. 
Published: March 2006

AbstractBackgroundThe State Hospital, Carstairs, is the sole high security psychiatric facility for Scotland and Northern Ireland.MethodThis study compares the female (n = 28) and male (n = 213) patients resident there between 1992 and 1993 using data derived from case‐note reviews and interviews with patients and staff.ResultsNearly three‐quarters of both the male and female populations had a primary diagnosis of schizophrenia, and secondary diagnoses of substance abuse and antisocial personality disorder were common. Female patients were more frequently admitted from other psychiatric hospitals, had less serious index offences and more minor previous convictions, and were less likely to be subject to a restriction order. They had more often experienced depressive symptoms and had significantly greater histories of self‐harm, physical and sexual abuse. At interview, nearly three‐quarters had active delusions and over half had recently behaved in an aggressive manner. Almost 90% were said not to require the security of the State Hospital.ConclusionsIt was concluded that mental illness and adverse social circumstances had combined to create a very disadvantaged group of women in high security psychiatric care in Scotland. As a group these women were inappropriately placed and their requirement was for intensive, rather than high security psychiatric care. Copyright © 2001 Whurr Publishers Ltd.
Violence and the prior victim–stalker relationship
Authors: Sheridan Lorraine , Davies Graham M. 
Published: March 2006

AbstractIntroductionPrevious research has suggested that stalkers who are ex‐partners are more likely to be violent towards their victims than acquaintance or stranger stalkers. A survey was conducted in Britain of 95 individuals who had contacted the Suzy Lamplugh Trust because they were being stalked.MethodEighty‐seven of the victims were female and seven were male. They were put into three categories: ex‐intimates, former acquaintances and strangers.ResultsEx‐intimates were the most aggressive of the three groups. Ex‐partners were overall the most intrusive in their behaviour and were also the most likely to threaten and assault third parties as well as their principal victim. Stranger stalkers, however, were significantly more likely than ex‐partners to be convicted of stalking‐related offences.ConclusionThe experiences of our sample would suggest that being stalked carries a high violence risk. Across relational subtypes, over 40% of respondents had experienced physical assault, including attempted murder, sexual assault, or a combination of these acts. Copyright © 2001 Whurr Publishers Ltd.
Psychosis and offending in British Columbia: characteristics of a secure hospital population
Authors: Hodelet Nicola 
Published: March 2006

AbstractIntroductionThere is an increased likelihood of violence in the mentally ill although the risk is small.AimsThe study aimed to ascertain the features in a secure hospital population that linked offending and mental illness.MethodA survey of patients in the high security hospital serving the province of British Columbia in Canada was carried out. Information on 175 mentally disordered offenders was extracted and included demographic data and specific characteristics of their offences, diagnoses and psychotic symptoms.ResultsThe most prevalent offences were crimes of violence, but 39% of patients were not primarily violent offenders. Almost two‐thirds (61%) had two or more diagnoses. A large majority of the patients were psychotic, schizophrenia being the most common diagnosis. There was a highly significant association between psychosis and violence, but the strength of the association was not increased by the presence of imperative hallucinations or delusions. The sample comprised various ethnic groups, one of which, Native Americans, was over‐represented. However, no association was found between violent offending and ethnicity, or age or years of illness.DiscussionThe study replicates previous findings of the link between violent offending and psychosis, but not a specific link between violent offending and psychotic drive. A surprising finding was a lack of association between violent offences and substance misuse. Copyright © 2001 Whurr Publishers Ltd.
Aggressive behaviour and social problem‐solving strategies: a review of the findings of a seven‐year follow‐up from childhood to late adolescence
Authors: Keltikangas‐Järvinen Liisa 
Published: March 2006

AbstractObjectivesIn a seven‐year follow‐up study, the author and colleagues examined the development of social skills from childhood to late adolescence, with a particular focus on aggressive behaviour. This paper presents a review of the most important findings of the project.Results and conclusionsSocial strategies explained aggressive behaviour, and changes of strategies predicted changes of behaviour. Aggressive behaviour was, however, very stable, and spontaneous change from an aggressive child to a sociable adolescent was not observed. This emphasizes an importance of early prevention of aggression. Disagreement between the children's and their parents' problem‐solving strategies was apparent, suggesting that interventions to reduce a child's aggression should be augmented by educating the parents about their children's behaviour. The role of peers was important because the child's concept of his or her strategies was dependent on his or her social acceptance, and this should be taken into account in interventions. Finally, as approval or disapproval of aggression is related to behaviour, moral cognitions should be included in the interventions. Copyright © 2001 Whurr Publishers Ltd.
‘Stop & Think!’: social problem‐solving therapy with personality‐disordered offenders
Authors: McMurran Mary , Fyffe Stephen , McCarthy Lucy , Duggan Conor , Latham Andrew 
Published: March 2006

AbstractBackgroundIn this paper, the authors describe ‘Stop & Think’ problem‐solving intervention implemented with personality‐disordered males resident on a dedicated personality disorder unit (PDU) within Arnold Lodge, a secure forensic psychiatric unit in Leicester, UK, as part of an integrated, multidisciplinary treatment programme. The problem‐solving approach consists of seven steps: (1) orientation, (2) problem definition, (3) goal setting, (4) generation of alternatives, (5) decision making, (6) action, and (7) evaluation. Efforts to integrate the ‘Stop & Think!’ problem‐solving process with individual and other therapies are described.ResultsUsing the Social Problem‐Solving Inventory‐Revised with 14 PDU patients at three and nine months after the commencement of ‘Stop & Think!’, significant improvements were recorded on all scales and subscales apart from Positive Problem Orientation. Change was maintained at 15 months for eight patients, with no significant further improvement. Recommendations for developments in assessment and treatment are made. Copyright © 2001 Whurr Publishers Ltd.