bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dominance in mitochondrial disorders
Authors: Zeviani M. , Carelli V. 
Published: April 2005

SummaryDominant traits are rare in mitochondrial disorders but include important nosological entities such as alterations of organellar biogenesis and abnormalities in the structural integrity of the mitochondrial genome, determined by mutations in genes involved in its maintenance and propagation. Both haplo‐insufficiency and ‘gain‐of‐function’ mechanisms underlie the pathogenesis of these disorders. Impairment in energy supply, abnormal mitochondrial trafficking, increased toxic damage by oxygen radicals, and mitochondrially driven apoptosis have been documented in different dominant syndromes. In addition, maternally inherited mutations of mitochondrial DNA can sometimes simulate dominant traits, mainly because of reduced penetrance and complex interaction with genetic and environmental factors.
Congenital brain malformations in mitochondrial disease
Authors: Brown G. K. 
Published: April 2005

SummaryThe majority of patients with mitochondrial disease have some degree of neuropathology and this is usually degenerative in nature. However, in a subset of mitochondrial diseases there are additional specific and characteristic congenital malformations in the brain. These developmental abnormalities are not unique to mitochondrial diseases and their association with only some conditions suggests that they are not simply due to energy deprivation or accumulation of metabolites such as lactic acid. Pathogenic mechanisms are at present unknown, but interference with neurotransmitter homeostasis, in addition to altered energy metabolism, may be important. The postnatal evolution of the neuropathology in these conditions and the type and pattern of the malformations suggest secondary degeneration of specific brain structures during fetal life rather than primary interference with developmental pathways.
Characteristics of glutamine metabolism in human precision-cut kidney slices: a 13C-NMR study
Authors: VITTORELLI Anne , GAUTHIER Catherine , MICHOUDET Christian , MARTIN Guy , BAVEREL Gabriel 
Published: April 2005

The metabolism of glutamine, a physiological substrate of the human kidney, plays a major role in systemic acid–base homoeostasis. Not only because of the limited availability of human renal tissue but also in part due to the lack of adequate cellular models, the mechanisms regulating the renal metabolism of this amino acid in humans have been poorly characterized. Therefore given the renewed interest in their use, human precision-cut renal cortical slices were incubated in Krebs–Henseleit medium (118 mM NaCl, 4.7 mM KCl, 1.18 mM KH2PO4, 1.18 mM MgSO4·7H2O, 24.9 mM NaHCO3 and 2.5 mM CaCl2·2H2O) with 2 mM unlabelled or 13C-labelled glutamine residues. After incubation, substrate utilization and product formation were measured by enzymatic and NMR spectroscopic methods. Glutamate accumulation tended to plateau but glutamine removal and ammonia, alanine and lactate production as well as flux through GLDH (glutamate dehydrogenase) increased to various extents with time for up to 4 h of incubation indicating the metabolic viability of the slices. Valproate, a stimulator of renal glutamine metabolism, markedly and in a dose-dependent fashion increased ammonia production. With [3-13C]glutamine as a substrate, and in the absence and presence of valproate, [13C]glutamate, [13C]alanine and [13C]lactate accounted for 81 and 96%, 34 and 63%, 30 and 46% of the glutamate, alanine and lactate accumulations measured enzymatically respectively. The slices also metabolized glutamine and retained their reactivity to valproate during incubations lasting for up to 48 h. These results demonstrate that, although endogenous metabolism substantially operates in the presence of glutamine, human precision-cut renal cortical slices are metabolically viable and strongly respond to the ammoniagenic effect of valproate. Thus, this experimental model is suitable for metabolic and pharmaco-toxicological studies.
Nitric oxide consumption through lipid peroxidation in brain cell suspensions and homogenates
Authors: KEYNES Robert G. , GRIFFITHS Charmaine H. , HALL Catherine , GARTHWAITE John 
Published: April 2005

Mechanisms which inactivate NO (nitric oxide) are probably important in governing the physiological and pathological effects of this ubiquitous signalling molecule. Cells isolated from the cerebellum, a brain region rich in the NO signalling pathway, consume NO avidly. This property was preserved in brain homogenates and required both particulate and supernatant fractions. A purified fraction of the particulate component was rich in phospholipids, and NO consumption was inhibited by procedures that inhibited lipid peroxidation, namely a transition metal chelator, the vitamin E analogue Trolox and ascorbate oxidase. The requirement for the supernatant was accounted for by its content of ascorbate which catalyses metal-dependent lipid peroxidation. The NO-degrading activity of the homogenate was mimicked by a representative mixture of brain lipids together with ascorbate and, under these conditions, the lipids underwent peroxidation. In a suspension of cerebellar cells, there was a continuous low level of lipid peroxidation, and consumption of NO by the cells was decreased by approx. 50% by lipid-peroxidation inhibitors. Lipid peroxidation was also abolished when NO was supplied at a continuously low rate (∼100 nM/min), which explains why NO consumption by this process is saturable. Part of the activity remaining after the inhibition of lipid peroxidation was accounted for by contaminating red blood cells, but there was also another component whose activity was greatly enhanced when the cells were maintained under air-equilibrated conditions. A similar NO-consuming process was present in cerebellar glial cells grown in tissue culture but not in blood platelets or leucocytes, suggesting a specialized mechanism.
Role of compartmentalized redox-active iron in hydrogen peroxide-induced DNA damage and apoptosis
Authors: TENOPOULOU Margarita , DOULIAS Paschalis-Thomas , BARBOUTI Alexandra , BRUNK Ulf , GALARIS Dimitrios 
Published: April 2005

Jurkat cells in culture were exposed to oxidative stress in the form of continuously generated hydrogen peroxide, obtained by the addition of glucose oxidase to the medium. This treatment induced a rapid, dose-dependent increase in the ICIP (intracellular calcein-chelatable iron pool). Early destabilization of lysosomal membranes and subsequent nuclear DNA strand breaks were also observed, as evaluated by the Acridine Orange relocation test and the comet assay respectively. Somewhat later, these effects were followed by a lowered mitochondrial membrane potential, with release of cytochrome c and apoptosis-inducing factor. These events were all prevented if cells were pretreated with the potent iron chelator DFO (desferrioxamine) for a period of time (2–3 h) long enough to allow the drug to reach the lysosomal compartment following fluid-phase endocytosis. The hydrophilic calcein, a cleavage product of calcein acetoxymethyl ester following the action of cytosolic esterases, obviously does not penetrate intact lysosomal membranes, thus explaining why ICIP increased dramatically following lysosomal rupture. The rapid decrease in ICIP after addition of DFO to the medium suggests draining of cytosolic iron to the medium, rather than penetration of DFO through the plasma membrane. Most importantly, these observations directly connect oxidative stress and resultant DNA damage with lysosomal rupture and the release of redox-active iron into the cytosol and, apparently, the nucleus.
Bifunctional promoter of type IV collagen COL4A5 and COL4A6 genes regulates the expression of α5 and α6 chains in a distinct cell-specific fashion
Authors: SUND Malin , MAESHIMA Yohei , KALLURI Raghu 
Published: April 2005

Type IV collagen is present ubiquitously in basement membranes. A bifunctional promoter regulates the expression of the α1/α2 genes, and the α3/α4 and the α5/α6 genes are also considered to be regulated by putative bifunctional promoters. Unlike the other type IV collagen chains, the α5(IV) and α6(IV) chains do not always co-localize and are present in distinct basement membranes. To address such dichotomy in the α5(IV) and α6(IV) gene regulation, we cloned a mouse genomic DNA fragment containing the promoter region between the two transcription start sites of these genes and we then placed this putative promoter sequence between the chloramphenicol acetyltransferase and Luciferase reporter genes, so that these genes would be transcribed in opposite directions in this unique construct. Glomerular endothelial cells and mesangial cells generate the kidney glomerular basement membrane, which always contains the α5(IV) chain but not the α6(IV) chain. In contrast, the basement membranes of Bowman's capsule and distal tubuli (produced by the tubular epithelial cells) contain the α6(IV) chain. We demonstrate that, in response to TGF-β (transforming growth factor β), epidermal growth factor, vascular endothelial growth factor and platelet-derived growth factor, expression from the α5(IV) gene is significantly enhanced in the glomerular endothelial cells and mesangial cells, but not expression from the α6(IV) gene. In contrast, the expression from the α6(IV) gene, and not that from the α5(IV) gene, was significantly enhanced in response to growth factors in the tubular epithelial cells. Our results demonstrate that the proximal bifunctional promoter regulates the expression of the α5(IV) and α6(IV) genes in a cell-specific manner and offers the first demonstration of the promoter plasticity in growth factor regulation of type IV collagen genes in different tissues of the body.
Pulling Out Threads from the Cosmic Tapestry: Defining Filaments of Galaxies
Authors: Pimbblet Kevin A. 
Published: April 2005

AbstractFilaments of galaxies are the dominant feature of modern large-scale redshift surveys. They can account for up to perhaps half of the baryonic mass budget of the Universe and their distribution and abundance can help constrain cosmological models. However, there remains no single, definitive way in which to detect, describe, and define what filaments are and their extent. This work examines a number of physically motivated, as well as statistical, methods that can be used to define filaments and examines their relative merits.
Impact of introducing guidelines on anticoagulant reversal
Authors: Salamat A. , Seaton J. , Watson H. G. 
Published: April 2005

summary. The production of clinical guidelines has become an accepted and lauded part of modern medicine. It is also widely perceived that these guidelines provide some sort of panacea for the problems that medicine faces. Our experience suggests otherwise. Triggered by on going anecdotal evidence of poor practice, we reviewed the effect on practice of a recently introduced local guideline on the management of major bleeding in patients on warfarin. Comparing 34 patients treated before and 48 patients after the introduction of the guideline, we found no significant improvement in prothrombin complex concentrate dosing or administration of vitamin K. The only improvement witnessed was in early assessment of the effect of the intervention on coagulation which improved from 10 to 35% of cases. Of major concern, in 10% of cases, there was no documentation to confirm or refute that prothrombin complex concentrate (PCC), which had been issued, had actually been administered to the patient.The production and widespread dissemination of this local guideline did not achieve significant improvement in clinical practice. Possible reasons for failure to adhere to the guideline are discussed.
An X‐ray microscopy perspective on the effect of glutaraldehyde fixation on cells
Authors: JEARANAIKOON S. , ABRAHAM‐PESKIR J. V. 
Published: April 2005

SummaryX‐ray microscopy (XRM) is the only microscopy technique that can provide high‐resolution (30 nm) imaging of biological specimens without the need to fix, stain or section them. We aim to determine the effect, if any, of glutaraldehyde fixation on algae cells from the XRM perspective and thus provide beneficial information for both X‐ray and electron microscopists on artefacts induced by glutaraldehyde fixation. Three species of microalgae, Microcystis aeruginosa, Anabaena spiroides and Chlorella vulgaris, were used in this study. XRM images were obtained from unfixed and glutaraldehyde‐fixed cells and cell diameter and percentage X‐ray absorbency were measured. The mean diameter of cells from fixed preparations was smaller than from unfixed preparations; the mean diameter of M. aeruginosa cells was significantly reduced from 3.92 µm in unfixed cells to 3.43 µm in fixed cells (P < 0.05); in C. vulgaris the diameter of cells was also significantly reduced from 3.50 µm in unfixed to 2.98 µm in fixed samples (P < 0.05); whereas there was no significant reduction in the diameter of A. spiroides cells (4.04–3.90 µm). The protein crosslinking mechanism of glutaraldehyde probably generated free water molecules, which play an important role in radiation damage induced by X‐rays. This was seen as mass loss and cell shrinkage, which in the present study occurred more frequently in fixed cells than in unfixed cells. In addition, we demonstrated that the uptake of glutaraldehyde by cells makes all protein constituents in the cell organize into a closely packed configuration, thus causing a rise in the percentage of X‐ray absorbency. In fixed cells, this rise was approximately by a factor of two compared with unfixed samples in which protein constituents inside the cell are arranged in their native form.
A South Australian population‐based study of congenital talipes equinovarus
Authors: Byron‐Scott R. , Sharpe P. , Hasler C. , Cundy P. , Hirte C. , Chan A. , Scott H. , Baghurst P. , Haan E. 
Published: April 2005

SummaryThe aims of this study were to provide a population‐based prevalence for congenital talipes equinovarus (CTEV), to conduct an epidemiological investigation into the risk factors for CTEV and describe associated features. The study used a retrospective case–control design of CTEV notified to the South Australian Birth Defects Register between 1986 and 1996 inclusive, linking characteristics of mother and baby from the perinatal data collection.The prevalence of isolated CTEV was 1.1/1000 total births (n = 231). Four factors were significantly associated with an increased risk of CTEV: maternal Aboriginal race (ORadj = 2.0; 95% CI 1.1, 3.6), male gender (ORadj = 2.4; 95% CI 1.8, 3.2), maternal anaemia (ORadj = 1.8; 95% CI 1.0, 2.9) and maternal hyperemesis (ORadj = 3.6; 95% CI 1.3, 9.8). The prevalence of CTEV associated with another birth defect or syndrome (n = 157) was 0.7/1000 total births. CTEV was associated with specific birth defects and also with oligohydramnios when another birth defect was present.
Risk factors for isolated talipes equinovarus in Western Australia, 1980–1994
Authors: Carey M. , Mylvaganam A. , Rouse I. , Bower C. 
Published: April 2005

SummaryA case–control study based on routinely collected data for a West Australian (WA) cohort of births born 1980–94 inclusive was used to identify potential risk factors for the foot deformity isolated talipes equinovarus.Race and sex were identified as risk factors and risk modifiers of the condition in WA infants. In comparison with their female counterparts, Aboriginal males were at greater risk of the deformity than Caucasian males (odd ratio [OR] 7.15, 95% confidence interval [CI] 2.68, 21.12 vs. OR 1.63, 95% CI 1.24, 2.15 respectively). Sex‐specific risk estimates of the deformity showed that Aboriginal males were at more than four times the risk of Caucasian males (OR 4.27, 95% CI 2.30, 8.25 respectively), but the risk amongst Aboriginal females was not dissimilar to the risk amongst Caucasian females (OR 1.12, 95% CI 0.49, 2.45).Intrauterine constraint of the fetus was not found to be an important contributing factor to the deformity after accounting for the effect of all risk factors modelled in multivariable analyses. Indicators of intrauterine constraint including prolonged gestation, high infant birthweight, young maternal age (<20 years) and breech presentation were not associated with excess numbers of isolated talipes equinovarus cases.Limited numbers of cases associated with other indicators of intrauterine constraint, including the specific categories of short maternal stature and a twin pregnancy prevented definitive conclusions regarding their association with the deformity. Improved data quality for gestational age estimates and oligohydramnios status are required before determining the prenatal risk impact of season of conception and of reduced amniotic fluid levels, respectively, on the occurrence of the deformity.
A survey of perceptions and attitudes among European surgeons towards the clinical impact and management of postoperative ileus
Authors: Kehlet H. , Williamson R. , Büchler M. W. , Beart R. W. 
Published: April 2005

AbstractObjective  Postoperative ileus (POI) can negatively affect patient recovery and morbidity, yet the lack of an internationally accepted definition and clinical management pathway for this condition suggest POI may be under‐recognized as a clinical problem. The purpose of this survey was therefore to assess current attitudes of surgeons towards the clinical impact and management of POI.Subjects and methods  Telephone interviews were conducted with 230 surgeons from hospitals in the UK, France, Germany, Italy and Spain.Results  Across Europe, there are differences in the terms surgeons use to refer to delayed recovery of gastrointestinal (GI) function and the symptoms, concerns and risks they associate with this condition. Furthermore, there is marked variation in the attitudes of European surgeons towards minimizing the risk of delayed recovery of GI function and in the strategies to manage POI. Additionally, some of the measures applied most commonly by European surgeons are in contrast to evidence in the literature indicating that they have no benefit for quicker resolution of GI function.Conclusion  The results suggest that there is a need for clearer definition of the factors that constitute POI, increased recognition of the impact of this condition and improved understanding of the most effective peri‐/postoperative care for surgical patients.
The role of prophylactic oophorectomy in women undergoing surgery for colorectal cancer
Authors: Banerjee S. , Kapur S. , Moran B. J. 
Published: April 2005

AbstractBackground  Current gynaecological practice is to remove surgically accessible ovaries with prior consent in post menopausal women to eradicate the risk of subsequent development of ovarian cancer. However in colorectal surgery opinion is divided, although evidence suggests that ovarian metastases from colorectal adenocarcinoma occur in 3–4% of cases.Methods  The review is based on published literature of the role of prophylactic oophrectomy in women undergoing surgery for colorectal cancer, obtained from Medline/PubMed and other online databases using the terms ‘prophylactic oophorectomy’ and ‘colon cancer’. Additional references were sourced by manually searching bibliographies of articles located.Results and conclusion  There is a paucity of published information and published reports have conflicting conclusions. A preliminary report of a randomised prospective trial suggests the probability of increased recurrence free survival in the oophorectomy group. It would seem appropriate to consider the necessity and possible benefits of oophorectomy in women prior to surgery for colorectal cancer. This would seem particularly relevant in distal sigmoid or upper rectal cancers when the ovaries or uterus may be directly invaded and curative surgery would involve en bloc resection. Post menopausal women with a family history of ovarian cancer should be advised to have oophorectomy.
Impact of faecal incontinence severity on health domains
Authors: Deutekom M. , Terra M. P. , Dobben A.C. , Dijkgraaf M. G. W. , Baeten C. G. M. I. , Stoker J. , Bossuyt P. M. M. 
Published: April 2005

AbstractObjective  Faecal incontinence is a problem that can have a major impact on the quality of life of those affected. Our aim was to relate the severity of faecal incontinence to the impact on several general health domains.Methods  Patients from a prospective diagnostic cohort study, performed in 16 medical centres in the Netherlands, were invited to the study. The severity of incontinence was determined with the Vaizey score, which ranges from 0 (continent) to 24 (totally incontinent). Based on their Vaizey score, patients were assigned to one of five severity categories. All patients completed the EuroQol‐5D instrument, which evaluates the existence of problems on five health domains: mobility, self‐care, usual activities, pain/discomfort and anxiety/depression.Results  Data from 259 consecutive patients (25 male) could be analysed. Their mean age was 59 years (SD ± 12). The mean duration of faecal incontinence was 8.1 years (SD ± 8). The proportion of patients reporting problems rose significantly with increasing severity of faecal incontinence in the domains of usual activities (ranging from 36% in the least severe group to 71% in the most severe group (P < 0.001)), pain/discomfort (ranging from 35% to 60%; P = 0.025), and anxiety/depression (ranging from 23% to 49%; P = 0.037). No significant trends could be observed in the domains of mobility and self‐care.Conclusion  There exists a significant relation between severity of incontinence and frequency of reported problems in the domains of usual activities, pain/discomfort and anxiety/depression.
Long‐term outcomes of restorative proctocolectomy for Crohn's disease and indeterminate colitis
Authors: Tekkis P. P. , Heriot A. G. , Smith O. , Smith J. J. , Windsor A. C. J. , Nicholls R. J. 
Published: April 2005

AbstractIntroduction  The present study aims to evaluate the short‐term and long‐term outcomes of patients undergoing restorative proctocolectomy (RPC) for Crohn's disease (CD) and Indeterminate colitis (IC) and to identify factors associated with adverse outcomes.Methods  A descriptive study of 52 patients with CD or IC from a total of 1652 patients undergoing primary or salvage RPC in a single tertiary referral centre between 1978 and 2003. Primary outcomes were ileal pouch failure (excision or indefinite diversion), adverse events and functional outcomes (bowel frequency, urgency and continence).Results  Patients with IC or IC favouring ulcerative colitis (Group 1, n = 26) had a pouch failure rate of 11.5%vs 57.5% for patients with CD or IC favouring CD (Group 2, n = 26). Pouch salvage surgery was undertaken in 15 patients with a 13.3% failure rate. Patients in Group 2 were 2.6 times more likely (95% CI: 0.96–7. No significant differences were evident between CD and IC patients with regards to pelvic sepsis (19.2%vs 15.4%), anastomotic stricture (23.1%vs 21.7%), small bowel obstruction (26.9%vs 26.9%) or pouchitis (15.4%vs 11.5%). The 24‐h bowel frequency (7.5 vs 8), faecal urgency, daytime or night time incontinence were similar between patients with CD or IC..17) to develop a pouch‐related fistula than patients in Group 1.Discussion  Crohn's disease and to a great extent indeterminate colitis favouring CD were both associated with high failure rates and postoperative pouch‐related fistula rates. Despite these problems, functional outcomes for patients with CD or IC were similar. Patients with IC should remain candidates for RPC but careful pre‐operative assessment is advised to exclude clinical signs favouring the diagnosis of CD. The complications associated with failure are extensive and the option of reconstructive surgery in patients with CD should be questioned.