bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synaptic scaffolding molecule interacts with Axin
Authors: Hirabayashi Susumu , Nishimura Wataru , Iida Junko , Kansaku Ai , Kishida Shosei , Kikuchi Akira , Tanaka Noriaki , Hata Yutaka 
Published: July 2004

AbstractSynaptic scaffolding molecule (S‐SCAM) is a synaptic protein that consists of PDZ domains, a guanylate kinase domain, and WW domains. It interacts with N‐methyl‐d‐aspartate receptor subunits, neuroligin, and β‐catenin. Here, we identified Axin as a novel binding partner of S‐SCAM. Axin was co‐immunoprecipitated with S‐SCAM from rat brain, detected in the post‐synaptic density fraction in rat brain subcellular fractionation, and partially co‐localized with S‐SCAM in neurons. The guanylate kinase domain of S‐SCAM directly bound to the GSK3β‐binding region of Axin. S‐SCAM formed a complex with β‐catenin and Axin, but competed with GSK3β for Axin‐binding. Thereby, S‐SCAM inhibited the Axin‐mediated phosphorylation of β‐catenin by GSK3β.
Molecular characterization of Dα6 and Dα7 nicotinic acetylcholine receptor subunits fromDrosophila: formation of a high‐affinity α‐bungarotoxin binding site revealed by expression of subunit chimeras
Authors: Lansdell Stuart J. , Millar Neil S. 
Published: July 2004

AbstractNicotinic acetylcholine receptors (nAChRs) mediate fast synaptic transmission in the insect brain and are target sites for neonicotinoid insecticides. Seven nAChR subunits (four α‐type and three β‐type) have been cloned previously fromDrosophila melanogaster, the model insect system and characterized by heterologous expression. Recently, three further putative nAChR α subunits (Dα5, Dα6 and Dα7) with sequence similarity to the vertebrate α7 subunit have been identified fromDrosophilagenome sequence data but there have been no reports, as yet, of their characterization by heterologous expression. In the present study, we report the first isolation of a full‐length Dα7 cDNA and the independent molecular cloning of Dα6. Binding of nicotinic radioligands was not detected to full‐length Dα6 or Dα7 subunits when expressed alone or when or co‐expressed with other nAChR subunits inDrosophilaor mammalian cell lines, but specific cell‐surface binding of [125I]α‐bungarotoxin (Kd = 0.68 ± 0.22 nm) and [3H]methyllycaconitine (Kd = 0.27 ± 0.06 nm) was detected after expression of a subunit chimera containing the ligand‐binding domains of Dα6 fused to the C‐terminal domain of the 5‐hydroxytryptamine receptor 5HT3A. Although cell‐surface binding was not detected with a Dα7/5HT3Αchimera expressed alone, co‐expression of the two subunit chimeras resulted in significantly enhanced levels of nicotinic radioligand binding (with no change in affinity). This is the first evidence for the formation of a nAChR binding site by heterologously expressedDrosophilanAChR subunits in the absence of a co‐expressed vertebrate nAChR subunit. In addition to the formation of homomeric nAChR complexes, evidence has been obtained from both radioligand binding and co‐immunoprecipitation studies for the co‐assembly of Dα6 and Dα7 into heteromeric cell surface complexes.
Nitrosylation precedes caspase‐3 activation and translocation of apoptosis‐inducing factor in neonatal rat cerebral hypoxia‐ischaemia
Authors: Zhu Changlian , Wang Xiaoyang , Qiu Lin , Peeters‐Scholte Cacha , Hagberg Henrik , Blomgren Klas 
Published: July 2004

AbstractExcessive nitric oxide (NO) production after cerebral hypoxia‐ischaemia (HI) may induce cellular injury in various ways, including reaction with superoxide to form the highly reactive peroxynitrite. We characterized the spatial and temporal formation of peroxynitrite through immunohistochemical detection of nitrosylated proteins. Nitrotyrosine immunoreactivity peaked around 3 h post‐HI and was detected in areas of injury, as judged by the loss of microtubule‐associated protein‐2 (MAP‐2) staining, in neurones, glia and endothelial cells. Nitrotyrosine staining co‐localized with three other cellular markers of injury, active caspase‐3, nuclear translocation of apoptosis‐inducing factor (AIF) and an oligonucleotide hairpin probe detecting specific DNA strand breaks. The number of nitrotyrosine‐positive cells at early time points outnumbered the cells positive for the other three markers of injury, indicating that nitrosylation preceded caspase‐3 activation. Pharmacological inhibition of neuronal and inducible nitric oxide synthase (nNOS and iNOS) using 2‐iminobiotin, which has been demonstrated earlier to be neuroprotective, significantly reduced nitrotyrosine formation and caspase‐3 activation, but not nuclear translocation of AIF, in cortex and striatum of the ipsilatral hemisphere. In summary, nitrotyrosine is an early marker of cellular injury and inhibition of nNOS and iNOS is a promising strategy for neuroprotection after perinatal HI.
Mammalian central nervous system trace amines. Pharmacologic amphetamines, physiologic neuromodulators
Authors: Berry Mark D. 
Published: July 2004

AbstractThe presence of the so‐called trace amines 2‐phenylethylamine, m‐tyramine, p‐tyramine, m‐octopamine, p‐octopamine and tryptamine in the mammalian central nervous system has been known for several decades. Despite much initial interest, these amines have largely been thought of as little more than metabolic by‐products. The recent description of a family of mammalian trace amine receptors has, however, seen a resurgence of interest in the physiological role of this class of compounds. Although the trace amines are well documented to cause amphetamine‐like effects, such responses only occur at concentrations multiple orders of magnitude above normal physiological levels. As such, it seems unlikely that these responses reflect the true physiological role of the trace amines. In this article previous studies showing responses to physiologically relevant concentrations of trace amines are reviewed, along with those showing a reciprocal relationship between trace amine levels and fluctuations in basal monoaminergic tone. On the basis of these studies it is hypothesized that the trace amines function as endogenous neuromodulators of classical monoamine neurotransmitters. These effects are seen as an altered neuronal sensitivity to monoamine neurotransmitters, with no change in neuronal excitability in the absence of neurotransmitter.
Maternally‐inherited Leigh syndrome‐related mutations bolster mitochondrial‐mediated apoptosis
Authors: Carrozzo Rosalba , Rizza Teresa , Stringaro Annarita , Pierini Roberta , Mormone Elisabetta , Santorelli Filippo M. , Malorni Walter , Matarrese Paola 
Published: July 2004

AbstractThe key role of mitochondria in the apoptotic process is well understood, but not many data are available regarding the specific role of mitochondrial DNA mutations in determining cell fate. We investigated whether two mitochondrial DNA mutations (L217R and L156R) associated with maternally‐inherited Leigh syndrome may play a specific role in triggering the apoptotic cascade. Considering that different nuclear genetic factors may influence the expression of mtDNA mutations, we used a 143BTK– osteosarcoma cell line deprived from its own mtDNA in order to insert mutated mtDNAs. Analysis of mitochondrial features in these cybrids indicated that both mitochondrial DNA mutations produced evidence of biochemical, functional and ultrastructural modifications of mitochondria, and that these modifications were associated with an increased apoptotic proneness. Cybrids were highly susceptible to two different apoptotic stimuli, tumour necrosis factor‐α and Staurosporin. The mechanism involved was the mitochondrial ‘intrinsic’ pathway, i.e. the caspase 9‐driven cascade. More importantly, our results also indicated that the polarization state of the mitochondrial membrane, i.e. a constitutive hyperpolarization detected in cybrid clones, played a specific role. Interestingly, the different effects of the two mutations in terms of susceptibility to apoptosis probably reflect the deeper bioenergetic defect associated with the L217R mutation. This work provides the first evidence that hyperpolarization of mitochondria may be a ‘risk factor’ for cells with a deep ATPase dysfunction, such as cells from patients with maternally‐inherited Leigh syndrome.
Geochemistry and microbiology of an impounded subterranean acidic water body at Mynydd Parys, Anglesey, Wales
Authors: COUPLAND KRIS , JOHNSON D. BARRIE 
Published: July 2004

ABSTRACTAcidic, metal‐rich water that had accumulated within two abandoned, adjacent copper mines in north Wales was removed to prevent its possible catastrophic release. About 274 000 m3 of acidic (pH ∼2.4) mine water was pumped out of the mines over a 14‐week period. Concentrations of dissolved species (iron, sulfate, aluminium, copper, manganese and zinc) increased as water at lower depths within the mines was accessed. The discharged water flowed through a small wetland area, reaching the sea about 3 km north of the mine site. Analysis of the water at three sampling stations revealed that there was very little removal of aluminium and most of the heavy metals present except (ferrous) iron, which was partially removed as a result of oxidation and hydrolysis of the resulting ferric iron. The dominant bacterium in the subterranean mine water, which was essentially devoid of oxygen, was the iron‐ and sulfur‐oxidizer Acidithiobacillus ferrooxidans. The microbial populations in the pumped mine water were monitored using combined cultivation‐dependent (isolation on solid media) and cultivation‐independent (terminal restriction fragment length polymorphism and clone library) techniques. Other bacteria detected in the mine water included other iron‐oxidizers (Leptospirillum spp., ‘Ferrimicrobium acidiphilum’ and Gallionella‐like organisms) and heterotrophic acidophiles (Acidiphilium, Acidisphaera and Acidobacterium). Archaeal clones were also detected; most of these were related to methanogens. Owing to the absence of an effective remediation strategy, an estimated 7.5 tonnes of copper, 3.1 tonnes of manganese, 14.8 tonnes of zinc and 15.3 tonnes of aluminium was discharged into the Irish Sea as a consequence of the dewatering of the mines.
Right ventricular long‐axis function in relation to left ventricular systolic function
Authors: Emilsson Kent 
Published: July 2004

SummaryA decrease in left ventricular (LV) systolic function is accompanied by a decrease in maximal relaxation velocity in LV long‐axis direction, but is it also accompanied by a decrease in right ventricular (RV) long‐axis function? To study this 35 consecutive patients were examined by echocardiography. Ejection fraction (LVEF) and mitral annulus motion (MAM) were used as indices of LV systolic function and tricuspid annulus motion (TAM), that is the systolic shortening in RV long‐axis direction, was used as an index of RV systolic long‐axis function. In the same way the maximal relaxation velocity in LV long‐axis direction, that is the maximal diastolic velocity of MAM (MDV MAM), has been suggested as an index of LV diastolic function the maximal diastolic velocity of TAM (MDV TAM) can be supposed to be an index of RV diastolic function measuring the maximal relaxation velocity in the RV long‐axis direction. A significant positive correlation was found between MDV TAM and MAM (r = 0·64, P<0001) and LVEF (r = 0·54, P = 0·001) and between TAM and the two studied indices of LV systolic function, with the highest correlation to MAM (r = 0·68, P<0·001) and the lowest to LVEF (r = 0·57, P<0·001). Thus, a decrease in LV systolic function is accompanied by a decrease in both systolic and diastolic RV long‐axis function, findings that probably are due to the close anatomical connection between the ventricles and to changes that occur in afterload of the RV secondary to LV systolic dysfunction.
Acute effects of nifedipine administration in pulmonary haemodynamics and oxygen delivery during exercise in patients with chronic obstructive pulmonary disease: implication of the angiotensin‐converting enzyme gene polymorphisms
Authors: Kanazawa Hiroshi , Tateishi Yoshitaka , Yoshikawa Junichi 
Published: July 2004

SummaryThe angiotensin‐converting enzyme (ACE) DD genotype is associated with exaggerated pulmonary hypertension and disturbance in tissue oxygenation during exercise in patients with chronic obstructive pulmonary disease (COPD). This study was designed to examine the acute effects of nifedipine administration in pulmonary haemodynamics and oxygen delivery during exercise in COPD patients with II, ID, and DD genotypes. Thirty‐three COPD patients (II = 12, ID = 11, DD = 10) with placebo or nifedipine (10 mg) underwent right heart catheterization with exercise, and systemic and pulmonary haemodynamic variables were examined. At rest, there was no significant difference in either mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR) or oxygen delivery (DO2) among the three groups. However, the magnitude of mPAP or PVR after exercise was the DD > ID > II genotype. In contrast, the magnitude of DO2 after exercise was the II > ID > DD genotype. We also found that nifedipine administration significantly decreased mPAP after exercise in all the three groups. However, we found no significant difference in PVR or DO2 between placebo and nifedipine administration in all the three groups. Thus, a single administration of nifedipine may not have the clinical efficacy for the treatment of pulmonary hypertension and impaired oxygen delivery during exercise in COPD patients with different ACE gene polymorphisms.
Intermittent venous compression, and the duration of hyperaemia in the common femoral artery
Authors: Morris Rhys J. , Woodcock John P. 
Published: July 2004

SummaryExternal compression of limbs to below‐diastolic pressure (venous compression) has been shown to produce a short‐lived hyperaemia in supply arteries. Intermittent pneumatic compression is currently under investigation therefore as a treatment for peripheral arterial disease. The optimal timing of the compression will depend on the duration of hyperaemia produced by a particular duration of compression, and the purpose of this work was to test that link. Nineteen healthy volunteers underwent intermittent compression of one leg with two compression cycles – one compressing for 10 s each time, the other for 1 min. Blood flow velocities in the common femoral artery was shown to increase on release of the compression by 38% (inter‐quartile range 27–56%) for the sequence with short duration compression, and by 57% (inter‐quartile range 37–87%) for the longer sequence (difference, P = 0·005, Wilcoxon). The hyperaemia duration above the baseline level was 37 s (inter‐quartile range 32–49 s) for the short sequence, and 54 s (inter‐quartile range 37–76 s) for the longer sequence (difference, P = 0·001, Wilcoxon). The magnitude of the change in the compression duration was not equalled by the difference in hyperaemia duration, suggesting that the physiological mechanism behind the hyperaemia is unlikely to be due solely to simple accumulation of metabolites, and a myogenic mechanism remains possible. Therapies for peripheral arterial disease need not employ long duration compression, as a greater percentage of time will be spent in hyperaemia with short duration intermittent compression.
C‐peptide: new findings and therapeutic implications in diabetes
Authors: Wahren John 
Published: July 2004

SummaryIn contrast to earlier views, new data indicate that proinsulin C‐peptide exerts important physiological effects and shows the characteristics of an endogenous peptide hormone. C‐peptide in nanomolar concentrations binds specifically to cell membranes, probably to a G‐protein coupled receptor. Ca2+‐ and MAP‐kinase dependent signalling pathways are activated, resulting in stimulation of Na+, K+‐ATPase and endothelial nitric oxide (NO) synthase, two enzyme systems known to be deficient in diabetes. C‐peptide may also interact synergistically with insulin signal transduction. Studies in intact animals and in patients with type 1 diabetes have demonstrated multifaceted effects. Thus, C‐peptide administration in streptozotocin‐diabetic animals results in normalization of diabetes‐induced glomerular hyperfiltration, reduction of urinary albumin excretion and diminished glomerular expansion. The former two effects have also been observed in type 1 diabetes patients given C‐peptide in replacement dose for up to 3 months. Peripheral nerve function and structure are likewise influenced by C‐peptide administration; sensory and motor nerve conduction velocities increase and nerve structural changes are diminished or reversed in diabetic rats. In patients with type 1 diabetes, beneficial effects have been demonstrated on sensory nerve conduction velocity, vibration perception and autonomic nerve function. C‐peptide also augments blood flow in several tissues in type 1 diabetes via its stimulation of endothelial NO release, emphasizing a role for C‐peptide in maintaining vascular homeostasis. Continued research is needed to establish whether, among the hormones from the islets of Langerhans, C‐peptide is the ugly duckling that – nearly 40 years after its discovery – may prove to be an endogenous peptide hormone of importance in the treatment of diabetic long‐term complications.
Psychometric properties of vision‐related quality of life questionnaires: a systematic review
Authors: De Boer Michiel R. , Moll Annette C. , De Vet Henrica C. W. , Terwee Caroline B. , Völker‐Dieben Hennie J. M. , Van Rens Ger H. M. B. 
Published: July 2004

AbstractThe increased attention for quality of life (QOL) as an outcome measure has led to the development of numerous questionnaires to assess this construct in the field of ophthalmology. This article presents a systematic review on QOL questionnaires for people with vision impairments. We systematically searched and selected the literature. Furthermore, a rating list with descriptive aspects (e.g. target population) and psychometric aspects (e.g. reproducibility) was developed. The 31 questionnaires that were included in the review were rated on the basis of criteria stated in this rating list. The questionnaires were mostly targeted at cataract patients or visually impaired persons in general. Only a few of the questionnaires demonstrated sufficient psychometric quality. A recent development is the (re‐)evaluation of questionnaires with Rasch analysis. This is one of the most important issues to which future research in this field should be directed.
Quality of light and quality of life – the effect of lighting adaptation among people with low vision
Authors: Brunnström Gunilla , Sörensen Stefan , Alsterstad Karin , Sjöstrand Johan 
Published: July 2004

AbstractPurpose:  The study has investigated the effect of lighting on the daily activities (ADL) of the visually impaired in their homes by comparison before and after light adjustments were made in the kitchen, hall and bathroom. It has also investigated the additional effects on the quality of life after providing task lighting in the living room.Method:  A total of 56 people were consecutively recruited from those receiving lighting adaptation help by the Low Vision Clinic in Göteborg. Ten persons did not complete the study. After medical examinations, lighting standards and psychosocial factors were charted. After lighting improvements were carried out in the kitchen, hall and bathroom, the subjects were randomly divided into two groups, an intervention and a comparison group. The task lighting in the living room was also improved for those included in the intervention group. Follow‐up interviews to determine ADL and quality of life were performed 6 months after lighting adaptation.Results:  A marked effect on quality of life of the lighting in the living room was found for the intervention group. The effect on ADL of the basic lighting adaptation in kitchen, hall and bathroom for both groups was significant for tasks carried out on the working surface in the kitchen. Other activities in the kitchen and in the bathroom tended to improve but changes were not significant.Conclusion:  The results confirm that it is possible to increase quality of life by improving the lighting conditions.
Measurements of preferred walking speed in subjects with central and peripheral vision loss
Authors: Soong G. P. , Lovie‐Kitchin J. E. , Brown B 
Published: July 2004

AbstractBackground:  Previous mobility studies have used Preferred Walking Speed (PWS) in order to determine the walking efficiency in terms of the Percent Preferred Walking Speed (PPWS) of visually impaired adults. PWS has been measured in previous studies using the sighted guide (SG) and non‐sighted guide (NSG) techniques. This study compared the NSG, SG and string (ST) (subjects walked by holding on lightly to a cardboard tube attached to a piece of string) techniques of measuring PWS in visually impaired subjects.Methods:  Forty visually impaired subjects with central and peripheral vision loss were recruited. PWS was measured using the NSG, SG and ST techniques. For each technique, PWS was determined by recording the time taken for a subject to walk an unobstructed, straight 20‐m corridor.Results:  There were no significant differences in PWS using the SG, NSG and ST techniques.Conclusion:  For assessing walking efficiency, either the SG, NSG or ST technique could be employed when measuring PWS in visually impaired subjects.
Ten years of glaucoma blindness in Fife 1990–99 and the implications for ophthalmology, optometry and rehabilitation services*
Authors: Sinclair A. , Hinds A. , Sanders R. 
Published: July 2004

AbstractThe aim of this study was to determine the characteristics of the patients in Fife who were registered as blind with a main diagnosis of glaucoma between 1990 and 1999. The case notes of 87 people were studied. The average age at registration was 78 years (S.D. = 14). By the time of first referral to hospital, more than half were already aware of visual loss. Forty‐five per cent of referrals had no optometry input. Compliance with treatment was poor in at least 26% of patients. Only 44% had glaucoma surgery. There were significant findings with regard to mental health, particularly dementia, which was eventually present in 24%. At least one‐third of patients had a hearing impairment. One‐third of those registered as blind could have been registered earlier. However, staff from the local provider of rehabilitation and social work services for the blind were shown to have provided prompt and helpful support to 95% of those registered. Consideration should be given to the way in which elderly patients with advanced glaucoma are managed, with awareness of mental health and hearing problems and emphasis on early referral to rehabilitation services.