bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ageing, oxidative stress, and mitochondrial uncoupling
Authors: Harper M.‐E. , Bevilacqua L. , Hagopian K. , Weindruch R. , Ramsey J. J. 
Published: November 2004

AbstractMitochondria are a cell's single greatest source of reactive oxygen species. Reactive oxygen species are important for many life sustaining processes of cells and tissues, but they can also induce cell damage and death. If their production and levels within cells is not effectively controlled, then the detrimental effects of oxidative stress can accumulate. Oxidative stress is widely thought to underpin many ageing processes, and the oxidative stress theory of ageing is one of the most widely acknowledged theories of ageing. As well as being the major source of reactive oxygen species, mitochondria are also a major site of oxidative damage. The purpose of this review is a concise and current review of the effects of oxidative stress and ageing on mitochondrial function. Emphasis is placed upon the roles of mitochondrial proton leak, the uncoupling proteins, and the anti‐ageing effects of caloric restriction.
Mitochondrial dysfunction measured in vivo
Authors: Marcinek D. J. 
Published: November 2004

AbstractAims:  Mitochondria are responsible for meeting the majority of the energetic demand of most tissues. They also play a major role in regulating cell survival. These dual roles of mitochondria place them at the centre of many pathologies leading to tissue degeneration and disruption of energy balance. The prominent role of mitochondria in ageing and disease has led to a tremendous growth in mitochondrial research at the cellular and molecular level. We describe below a new non‐invasive approach to measure mitochondrial function that will bridge the gap between our understanding of mitochondrial function in vitro and that in the intact organism.Methods and Results:  This approach uses optical and magnetic resonance spectroscopy to measure in vivo O2 consumption and ATP synthesis rates, respectively, from skeletal muscle. These values lead to a quantitative assessment of the mitochondrial ATP/O2 or P/O. The P/O represents the efficiency of coupling between phosphorylation and oxygen consumption in the mitochondria, which is a measure of mitochondrial dysfunction.Conclusions:  This work represents a significant advance in research on the role of mitochondria in degenerative disease and ageing because it allows a quantitative measure of mitochondrial pathology in vivo. The non‐invasive nature of this approach also enables repeated measures of mitochondrial function on the same individual, thereby making this a potentially useful diagnostic technique. The results from this work have led to insights into the coupling of ATP synthesis to oxidation and the regulation of oxidative phosphorylation by intracellular PO2.
Comparative analysis and development of microsatellite markers on swine (Sus scrofa) chromosome 1qter
Authors: Mikawa S. , Shimanuki S. , Morozumi T. , Domukai M. , Shinkai H. , Uchida Y. , Mikawa A. , Miyake M. , Miyake Y. , Hayashi N. , Kusumoto H. , Uenishi H. , Hayashi T. , Awata T. 
Published: November 2004

SummarySeveral quantitative trait loci (QTL) have been detected on SSC1qter (Sus scrofa chromosome 1qter), including QTL for the number of vertebrae, as reported in our previous study. To provide the tools for analysis of QTLs on SSC1qter, we constructed a comparative map of swine and human. In addition, we identified 26 swine STSs and mapped 16 of them on SSC1qter using the INRA – University of Minnesota porcine radiation hybrid (IMpRH) panel. We screened a BAC library using these swine STSs and developed 35 new polymorphic microsatellite markers from the BAC clones, of which 26 were informative in our reference family. We also mapped nine microsatellite markers we had isolated previously. Consequently a total of 44 new polymorphic microsatellite markers were located within a 60‐cM region of SSC1qter, spanning from SW1092 to the telomere.
Altered patterns of the interferon‐inducible gene IFI16 expression in head and neck squamous cell carcinoma: immunohistochemical study including correlation with retinoblastoma protein, human papillomavirus infection and proliferation index
Authors: Azzimonti B , Pagano M , Mondini M , De Andrea M , Valente G , Monga G , Tommasino M , Aluffi P , Landolfo S , Gariglio M 
Published: November 2004

Aims:  To investigate whether the expression of interferon (IFN)‐inducible gene IFI16 is inversely related to proliferative activity in vivo, we compared immunohistochemical reactivity of IFI16 in a series of head and neck squamous cell carcinomas (HNSCCs) with their proliferation index and the cell cycle regulator pRb. As human papillomavirus (HPV) infection is manifested by changes in the function or expression level of host genes such as IFN‐inducible genes, we also investigated the presence of HPV DNA to determine whether head and neck cancers associated with HPV DNA can be distinguished from tumours that are presumably transformed by other mechanisms.Methods:  Thirty‐six HNSCCs were evaluated for IFI16, pRb and Ki67 expression by immunohistochemistry. The presence of HPV was also detected by polymerase chain reaction. Nine tumours were located in the oropharynx (tonsillar area) and 27 in the larynx.Results:  HPV DNA was found in 14 of 25 (56%) laryngeal SCCs and in five of nine (56%) tonsillar SCC specimens examined; 17 out of the 19 HPV‐DNA‐positive cases showed high‐grade IFI16 expression. Overall, proliferative activity was significantly related to tumour differentiation and histological grading. IFI16 protein expression was significantly inversely correlated with Ki67 (P = 0.039). Low‐proliferating tumours positive for IFI16 staining showed a marked expression of pRb and a better prognosis than those whose tumours had low IFI16, pRb levels and a high proliferation index.Conclusions:  To our knowledge, this is the first expression analysis of the IFN‐inducible IFI16 gene in HNSCC. Low‐proliferating tumours positive for IFI16 staining showed a marked expression of pRb and a better prognosis than those whose tumours had low IFI16, pRb levels and a high proliferation index.
Comparative analysis of COX‐2, vascular endothelial growth factor and microvessel density in human renal cell carcinomas
Authors: Hemmerlein B , Galuschka L , Putzer N , Zischkau S , Heuser M 
Published: November 2004

Aims:  Cyclooxygenase‐2 (COX‐2) and vascular endothelial growth factor (VEGF) are frequently up‐regulated in malignant tumours and play a role in proliferation, apoptosis, angiogenesis and tumour invasion. In the present study, the expression of COX‐2 and VEGF in renal cell carcinoma (RCC) was analysed and correlated with the microvessel density (MVD).Methods and results:  COX‐2 and VEGF were analysed by realtime reverse transcriptase‐polymerase chain reaction and immunohistochemistry. The MVD was assessed by CD31 immunohistochemistry. The expression of COX‐2 and VEGF was determined in the RCC cell lines A498 and Caki‐1 under short‐term hypoxia and in multicellular tumour cell aggregates. COX‐2 was expressed in RCC by tumour epithelia, endothelia and macrophages in areas of cystic tumour regression and tumour necrosis. COX‐2 protein in RCC was not altered in comparison with normal renal tissue. VEGF mRNA was up‐regulated in RCC and positively correlated with MVD. RCC with high up‐regulation of VEGF mRNA showed weak intracytoplasmic expression of VEGF in tumour cells. Intracytoplasmic VEGF protein expression was negatively correlated with MVD. In RCC with necrosis the MVD was reduced in comparison with RCC without necrosis. A498 RCC cells down‐regulated COX‐2 and up‐regulated VEGF under conditions of hypoxia. In Caki‐1 cells COX‐2 expression remained stable, whereas VEGF was significantly up‐regulated. In multicellular A498 cell aggregates COX‐2 and VEGF were up‐regulated centrally, whereas no gradient was found in Caki‐1 cells.Conclusions:  COX‐2 and VEGF are potential therapeutic targets because COX‐2 and VEGF are expressed in RCC and associated cell populations such as endothelia and monocytes/macrophages.
Polymerized α1‐antitrypsin is present on lung vascular endothelium. New insights into the biological significance of α1‐antitrypsin polymerization
Authors: Aldonyte R , Jansson L , Ljungberg O , Larsson S , Janciauskiene S 
Published: November 2004

Aims:  The damage to lung tissue in chronic obstructive pulmonary disease (COPD) may involve the progressive loss of pulmonary vascular endothelial cells. Endothelial binding of α1‐antitrypsin (α1‐AT) derived from plasma has been identified, and α1‐AT deficiency is a known genetic risk factor associated with α1‐AT polymerization and COPD development. Therefore, in the present study we aimed to investigate if α1‐AT is present on the lung vascular endothelium, and if it is in a polymeric form.Methods and results:  Postmortem paraffin‐embedded tissue specimens from 15 COPD (chronic bronchitis and emphysema) cases with and without Z α1‐AT (Glu342Lys) deficiency and from 10 cases without signs of COPD were studied. Immunohistochemistry was performed using the streptavidin–biotin method with a monoclonal ATZ11 antibody specific for polymeric α1‐AT, and polyclonal antibodies against human α1‐AT and neutrophil elastase. Vascular endothelium showed intense staining for α1‐AT with the ATZ11 antibody in all cases; however, intensity of staining in patients with α1‐AT deficiency was greater. No endothelial staining was observed with the anti‐elastase antibody.Conclusions:  This is the first demonstration that α1‐AT bound to the vascular endothelium of lungs is in a polymeric form, which also suggests a possible previously unknown role for polymeric α1‐AT in vivo.
Presence of nanobacteria in psammoma bodies of ovarian cancer: evidence for pathogenetic role in intratumoral biomineralization
Authors: Hudelist G , Singer C F , Kubista E , Manavi M , Mueller R , Pischinger K , Czerwenka K 
Published: November 2004

Aims:  The presence of laminated, calcified extracellular debris known as psammoma bodies is a well‐known histomorphological feature of ovarian adenocarcinomas and other human malignancies. Biomineralization has recently been found to be associated with a group of extremely small Gram‐negative bacteria capable of precipitating calcium salts. The aim of the present study was to evaluate a possible pathogenic link between the development of psammoma bodies and nanobacteria infection.Material and results:  Immunohistochemical staining and reverse transcriptase‐polymerase chain reaction (RT‐PCR) were used to analyse nanobacterial protein and gene expression in eight psammona body‐containing adenocarcinomas and in 10 malignant ovarian tumours without signs of biomineralization. Nanobacterial proteins were detected in eight out of eight (100%) psammoma‐positive tumour samples. Conversely, none of the 10 psammoma‐negative tissues (0%) was positive for nanobacterial antigens. Furthermore, nanobacterial mRNA was detectable in all of the four tissues (100%) that contained psammoma bodies, but was absent in all 10 ovarian cystadenocarcinomas (0%) that were psammoma negative.Conclusions:  We found a 100% concordance between the expression of nanobacteria and the presence of psammoma bodies in malignant ovarian tumours. Several lines of evidence suggest the involvement of these organisms in the process of biomineralization. We therefore conclude that nanobacterial infection of malignant ovarian tissue contributes to mechanisms leading to the formation of calcified deposits known as psammoma bodies.
Transforming teaching and learning: embedding ICT into everyday classroom practices
Authors: Sutherland R. , Armstrong V. , Barnes S. , Brawn R. , Breeze N. , Gall M. , Matthewman S. , Olivero F. , Taylor A. , Triggs P. , Wishart J. , John P. 
Published: November 2004

AbstractDrawing on socio‐cultural theory, this paper describes how teams of teachers and researchers have developed ways of embedding information and communications technology (ICT) into everyday classroom practices to enhance learning. The focus is on teaching and learning across a range of subjects: English, history, geography, mathematics, modern foreign languages, music and science. The influence of young people's out‐of‐school uses of ICT on in‐school learning is discussed. The creative tension between idiosyncratic and institutional knowledge construction is emphasised and we argue that this is exacerbated by the use of ICT in the classroom.
Gene frequencies of the HPA‐15 (Gov) platelet alloantigen system in Brazilians
Authors: Cardone J. D. B. , Chiba A. K. , Boturão‐Neto E. , Vieira‐Filho J. P. B. , Bordin J. O. 
Published: November 2004

Summary.  The HPA‐15 (Gov) alloantigen is a biallelic co‐dominant system on human platelets, and its allele HPA‐15a and HPA‐15b differ by an A→C single nucleotide polymorphism at nucleotide 2108 of the coding sequence resulting in a Tyr682Ser substitution in the mature CD109 glycoprotein.Employing the polymerase chain reaction‐restriction fragment length polymorphism technique, we determined the HPA‐15 gene frequencies among 276 subjects of distinct Brazilian ethnic groups including, 15 Caucasians, 15 African Brazilians, 15 Orientals, 106 Amazon Xikrin Indians, 31 Amazon Gaviões Indians and 94 blood donors.The calculated HPA‐15a and HPA‐15b allele frequencies found in Caucasians (0.53/0.47), African Brazilians (0.57/0.43), Orientals (0.57/0.43) and Brazilian blood donors (0.52/0.48) did not differ significantly. However, the HPA‐15a and HPA‐15b gene frequencies of Xikrin Indians (0.78/0.22) were significantly different from that of all other groups (P < 0·01). The HPA‐15a/a, HPA‐15a/b and HPA‐15b/b genotype frequencies observed in Gaviões Indians were significantly different from those seen in African Brazilians (P = 0·04) and blood donors (P = 0·017).The present data showed that the distribution of the HPA‐15 (Gov) system alleles observed among the Brazilian population is quite similar to the distributions already reported among Asian, Canadian and European populations. Moreover, the data indicated differences in the frequency of the HPA‐15 system between Amazon Indians and other distinct Brazilian ethnic groups suggesting that Amerindians would be at higher risk of HPA‐15 alloimmunization in the need of receiving blood components collected from blood donors of other ethnic groups.
A novel method for the detection of bacteria in platelet concentrates utilizing oxygen consumption as a marker for bacterial growth
Authors: McDonald C. P. , Colvin J. , Smith R. , Wilkins K. , Robbins S. , Barbara J. A. J. 
Published: November 2004

Summary.  Bacterial transfusion–transmission remains a significant problem in transfusion medicine. Diversion and improved donor arm disinfection has been introduced by blood services to reduce bacterial transmissions. These interventions are not 100% effective and, therefore, there is still a requirement to screen blood donations, particularly platelet concentrates which are responsible for the majority of transmissions. Pall BDS, a novel bacterial testing system, detects the presence of bacteria in platelet concentrates by measuring the reduction in oxygen content associated with bacterial growth.Buffy coat‐derived pooled platelet concentrates were spiked with 12 aerobic and two anaerobic organisms (one species per bag, n = 10) at 100–700 cfu mL−1. Samples were taken into Pall BDS sample pouches and incubated for 0, 24, 30 and 48 h. An initial incubation was undertaken at 35 °C for 24 h and subsequent incubation was at 22 °C. At the end of the incubation period the oxygen content in the Pall BDS pouches was measured using a gas analyser. An oxygen content less than or equal to 19·5% was deemed to be positive. Pall BDS pouches tested positive in 80, 94 and 98% units spiked with aerobic bacteria at 24, 30 and 48 h, respectively. Anaerobic bacteria were not detected by the system. Positive BDS pouches contained 106 cfu mL−1 or greater. The system was simple and easy to perform. Pall BDS has a closed sampling system which prevents exogenous contamination. This initial study indicates that the Pall BDS offers a practicable system for detecting bacteria present in leucodepleted platelet concentrates.
Valganciclovir prophylaxis in patients at high risk for the development of cytomegalovirus disease
Authors: Taber D.J. , Ashcraft E. , Baillie G.M. , Berkman S. , Rogers J. , Baliga P.K. , Rajagopalan P.R. , Lin A. , Emovon O. , Afzal F. , Chavin K.D. 
Published: November 2004

Abstract: Background. Despite advances in antiviral therapies, cytomegalovirus (CMV) remains the leading opportunistic infection in the transplant population. Valganciclovir (VGC), the l‐valyl ester prodrug of ganciclovir (GCV), provides an excellent oral alternative to GCV for the prevention of CMV in transplant recipients. We investigated the use of VGC for CMV prevention in high‐risk renal and pancreas transplant recipients.Methods. Patients at high risk for development of CMV disease were defined as either those who had donor positive, recipient‐negative serostatus (D+/R−), or those who received antilymphocyte antibody (ALA) therapy for either rejection treatment or induction. A retrospective review was conducted of all kidney and pancreas transplants performed between August 2001 and December 2003. A total of 341 transplants were performed, of which 109 received VGC, and 88 were included in this analysis.Results. The overall incidence of CMV disease was 5.7% (5/88). All of the CMV episodes were in patients who were D+/R− (17.2% [5/29] versus 0% [0/59], P<0.001). Of these patients, all the episodes of CMV were in patients who received VGC prophylaxis for<100 days post transplant (29% [5/17] versus 0% [0/12], P=0.06). The overall incidence of leukopenia was 11% and thrombocytopenia was 7%, with the incidence between the D+/R− group and the ALA group being similar.Conclusion. VGC is an effective agent in preventing CMV disease in kidney and pancreas transplant recipients who are at high risk for developing the disease. The optimal length of prophylaxis in D+/R− patients is still undefined, while 3 months of prophylaxis appears to be sufficient in patients who received ALA therapy.
Should Actuarial Risk Assessments be Used with Sex Offenders who are Intellectually Disabled?
Authors: Harris Andrew J. R. , Tough Susan 
Published: November 2004

Background  Objective actuarial assessments are critical for making risk decisions, determining the necessary level of supervision and intensity of treatment (Andrews & Bonta 2003). This paper reviews the history of organized risk assessment and discusses some issues in current attitudes towards sexual offenders with intellectual disabilities.Method  We present two risk assessment tools (RRASOR and STABLE‐2000) that appear to have practical utility with this population. Data are presented from a community sample of 81 sexual offenders who are intellectually disabled suggesting that the RRASOR may provide a useful metric of risk for this population. Dynamic risk is assessed using the STABLE‐2000. This tool, based on 16 areas empirically associated with sexual recidivism, samples the individuals’ current behaviour, skill deficits and personality factors. Change in these factors serves to flag the supervisor to changing risk levels.Conclusions  In addressing the question of whether we should seek special risk measures normed on people with intellectually disabilities, given the current lack of alternative tools, we conclude that it is reasonable to make use of the risk assessments that have been validated on the general sex offender population.
Risk Assessment: Actuarial Prediction and Clinical Judgement of Offending Incidents and Behaviour for Intellectual Disability Services
Authors: Lindsay William R. , Beail Nigel 
Published: November 2004

Background Research on prediction of violent and sexual offending behaviour has developed considerably in the mainstream criminological literature. Apart from one publication [Quinsey (2004)Offenfers with Developmental Disabilities, pp. 131–142] this has not been extended to the field of intellectual disabilities.Methods Work on actuarial instruments, dynamic variables, clinical judgement and structured clinical judgement is reviewed.Results A number of studies comparing actuarial instruments in terms of their predictive validity are reviewed. Relative effectiveness and applicability to intellectual disability is considered. A framework for dynamic variables is outlined and the importance of dynamic variables for inclusion in risk prediction is established. Strengths and limitations of clinical judgement are reported and the importance of reliability is noted. Finally, structured clinical judgement is reviewed in terms of the way in which it combines the other three groups of variables.Conclusions The information regarding different methods of risk assessment is integrated with research and opinion contained in the Special Issue. Risk prediction will always be a judgement and as such there will always be errors in judgement. As clinicians, researchers and policy makers it is our duty to employ the latest research information to make predictions that are as accurate as possible. However, we must also help to promote a culture that can be tolerant of inevitable errors.
Assessment of Risk Manageability of Intellectually Disabled Sex Offenders
Authors: Boer Douglas P. , Tough Susan , Haaven James 
Published: November 2004

Background There are no validated risk assessment tools for intellectually disabled (ID) sex offenders, with the exception of the work of Lindsayet al.[Journal of Applied Research in Intellectual Disabilities(2004)17: 267] regarding the prediction of risk for aggressive behaviour of ID offenders in residential settings. ID sex offenders comprise a neglected subgroup, and one that poses unique challenges and rewards for clinicians.Methods and purpose Recent work by Tough [Tough S. (2001)Validation of Two Standard Assessments (RRASOR, 1997; STATIC‐99, 1999) on a Sample of Adult Males who are Intellectually Disabled with Significant Cognitive Deficits. Master's Thesis, University of Toronto, Toronto, ON, Canada] examined the utility of the Rapid Risk Assessment for Sexual Offence Recidivism [RRASOR;Hanson R. (1997)The Development of a Brief Actuarial Risk Scale for Sexual Offence Recidivism, User Report 97‐04. Department of the Solicitor General of Canada, Ottawa, ON, Canada.] and the Static‐99 [Hanson R. K. & Thornton D. (1999)Static‐99: Improving Actuarial Risk Assessments for Sex Offenders, User Report 99‐02. Department of the Solicitor General of Canada, Ottawa, ON, Canada] for ID sex offenders. She determined that the Static‐99 may overestimate risk in ID sex offenders and that the RRASOR seemed to be a more accurate tool for these offenders. These actuarial tools provide a ‘risk baseline’, which helps in determining treatment intensity and level of supervision, but do not provide much help in designing treatment plans or management strategies based on the needs of the individual client. Hence, all three authors have developed risk management strategies in their work with ID sex offenders based largely on dynamic factors. This work has produced the present assessment.Outcome The present paper outlines a convergent approach which uses the information provided by static actuarial instruments and relevant dynamic factors as an introduction to the formation of a risk management strategies instrument for ID sex offenders. Thirty suggested items, split into four categories (chronic dynamic and acute dynamic for staff and environment; chronic dynamic and acute dynamic for offenders) are listed along with brief explanations of these items.