Major Determinant (major + determinant)

Distribution by Scientific Domains
Distribution within Medical Sciences


Selected Abstracts


Fluctuation in Autonomic Tone is a Major Determinant of Sustained Atrial Arrhythmias in Patients with Focal Ectopy Originating from the Pulmonary Veins

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 3 2001
MARC ZIMMERMANN M.D.
Autonomic Variations in Focal AF. Introduction: This study was designed to analyze dynamic changes in autonomic tone preceding the onset of sustained atrial arrhythmias in patients with focal atrial fibrillation (AF) to determine why patients with frequent discharge from the arrhythmogenic foci develop sustained AF. Methods and Results: Holter tapes from 13 patients (10 men and 3 women; mean age 53 ± 5 years) with paroxysmal "lone" AF (mean 18 ± 13 episodes per week) and a proven focal origin (pulmonary veins in all cases) were analyzed. A total of 38 episodes of sustained AF (> 30 min) were recorded and submitted to frequency-domain heart rate variability analysis. Six periods were studied using repeated measures analysis of variance: the 24,hour period, the hour preceding AF, and the 20 minutes before AF divided into four 5,minute periods. A significant increase in high-frequency (HF, HF-NU) components was observed during the 20 minutes preceding AF (P = 0.003 and 0.002, respectively), together with a progressive decrease in normalized low-frequency (LF-NU) components (P = 0.035). An increase in LF/HF ratio followed by a linear decrease starting 15 minutes before sustained AF also was observed, indicating fluctuations in autonomic tone, with a primary increase in adrenergic drive followed by a marked modulation toward vagal predominance immediately before AF onset. Conclusion: In patients with focal ectopy originating from the pulmonary veins, sustained episodes of atrial arrhythmias are mainly dependent on variations of autonomic tone, with a significant shift toward vagal predominance before AF onset. [source]


Gender differences in physical activity and its determinants in rural adults in Korea

JOURNAL OF CLINICAL NURSING, Issue 5-6 2010
Hyun Kyung Kim
Aim., This study aimed to examine gender differences in physical activity and its determinants among rural adults in Korea. Background., Only limited studies exist that examined gender differences in physical activity in Korean adults. Major determinants for physical activity such as self-efficacy, benefits and barriers have been studied, but little is known about their gender differences. Nurses promoting and teaching adults to increase physical activity need data for evidence-based practice. Design., A cross-sectional descriptive design was used. Method., Participants were 481 adults living in a rural area of Korea. The physical activity status, exercise self-efficacy, benefits, barriers and sociodemographics were compared between men and women. Descriptive statistics, t -test and binary logistic regression were used for data analysis. Results., The physical activity status, perceived self-efficacy and benefits of physical activity in women were significantly lower than those of men. For men, only self-efficacy was statistically significant in explaining recommended physical activity as well as physical activity participation. However, for women, benefits and barriers as well as self-efficacy significantly explained their participation of physical activity, but not the recommended physical activity. Unlike men, women's physical activity was significantly associated with sociodemographic factors. Conclusion., Gender differences found in this study should be the basis for evidence-based nursing practice. Tailored nursing interventions based on gender would improve physical activity of rural adults in Korea and beyond. Relevance to clinical practice., Nurses providing care for rural adults should know the gender differences in the determinants of physical activity and provide gender-specific interventions to improve their physical activity. [source]


Skeletal muscle fibre diversity and the underlying mechanisms

ACTA PHYSIOLOGICA, Issue 4 2010
M. Canepari
Abstract The review first briefly summarizes how myosin isoforms have been identified as the major determinant of the functional variability among skeletal muscle fibres. The latter feature is a major characteristic of muscle fibres and a major basis of skeletal muscle heterogeneity and plasticity in vivo. Then, evidence is reported, which indicates that the properties of muscle fibres can vary with no change in the myosin isoform they express. Moreover, the physiological and pathological conditions (ageing, disuse, exercise training, muscular dystrophy) in which such myosin isoform independent change in functional properties occurs and the possible underlying mechanisms are considered. Finally, the known molecular bases of the functional differences among slow and fast isoforms are briefly dealt with. [source]


Regulation of skeletal muscle mitochondrial function: genes to proteins

ACTA PHYSIOLOGICA, Issue 4 2010
I. R. Lanza
Abstract The impact of ageing on mitochondrial function and the deterministic role of mitochondria on senescence continue to be topics of vigorous debate. Many studies report that skeletal muscle mitochondrial content and function are reduced with ageing and metabolic diseases associated with insulin resistance. However, an accumulating body of literature suggests that physical inactivity typical of ageing may be a more important determinant of mitochondrial function than chronological age, per se. Reports of age-related declines in mitochondrial function have spawned a vast body of literature devoted to understanding the underlying mechanisms. These mechanisms include decreased abundance of mtDNA, reduced mRNA levels, as well as decreased synthesis and expression of mitochondrial proteins, ultimately resulting in decreased function of the whole organelle. Effective therapies to prevent, reverse or delay the onset of the aforementioned mitochondrial changes, regardless of their inevitability or precise underlying causes, require an intimate understanding of the processes that regulate mitochondrial biogenesis, which necessitates the coordinated regulation of nuclear and mitochondrial genomes. Herein we review the current thinking on regulation of mitochondrial biogenesis by transcription factors and transcriptional co-activators and the role of hormones and exercise in initiating this process. We review how exercise may help preserve mitochondrial content and functionality across the lifespan, and how physical inactivity is emerging as a major determinant of many age-associated changes at the level of the mitochondrion. We also review evidence that some mitochondrial changes with ageing are independent of exercise or physical activity and appear to be inevitable consequences of old age. [source]


Plasma protein charge: a major determinant of fluid exchange

ACTA PHYSIOLOGICA, Issue 4 2008
Helge Wiig
No abstract is available for this article. [source]


Plasma renin in mice with one or two renin genes

ACTA PHYSIOLOGICA, Issue 4 2004
P. B. Hansen
Abstract Aim:, In the present study we have investigated whether the presence of a second renin gene exerts an overriding influence on plasma renin such that mice with two renin genes have consistently higher renin levels than mice with only one renin gene. Methods:, Plasma renin was determined as the rate of angiotensin I generation using a radioimmunoassay (RIA) kit with (plasma renin concentration, PRC) or without (plasma renin activity, PRA) the addition of purified rat angiotensinogen as substrate. Results:, In male 129SvJ, DBA/2 and Swiss Webster mice, strains possessing both Ren-1 and Ren-2, PRC (ng Ang I mL,1 h,1) averaged 178 ± 36, 563 ± 57 and 550 ± 43 while PRA was 2.9 ± 0.5, 3.6 ± 0.8 and 7.8 ± 1.2. In male C57BL/6, C3H and BALB/c mice that express only Ren-1, PRC averaged 426 ± 133, 917 ± 105 and 315 ± 72, and PRA was 3.4 ± 1.0, 6.9 ± 1.7 and 4.5 ± 1.2. In the two renin gene A1AR,/, mice compared with the one renin gene A1AR+/+, PRC averaged 538 ± 321 and 415 ± 159 while PRA averaged 3.2 ± 1.1 and 4.4 ± 1.4 ng Ang I mL,1 h,1. Aldosterone levels showed no significant differences between one renin (C57BL/6, C3H and BALB/c) and two renin (129SvJ, DBA/2 and Swiss Webster) gene mice. Furthermore, by quantitative real-time polymerase chain reaction (RT-PCR) we found no correlation between the number of renin genes and whole kidney renin mRNA levels from one and two renin gene mice. Conclusion:, Our data show that baseline plasma renin is not systematically higher in mice with two renin genes than in one renin gene mice. Thus, the presence of a second renin gene does not seem to be a major determinant of differences in PRC between different mouse strains. [source]


Genetic basis of rett syndrome

DEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2002
Ignatia B. Van den Veyver
Abstract The origin of Rett syndrome has long been debated, but several observations have suggested an X-linked dominant inheritance pattern. We and others have pursued an exclusion-mapping strategy using DNA from a small number of familial Rett syndrome cases. This work resulted in the narrowing of the region likely to harbor the mutated gene to Xq27.3-Xqter. After systematic exclusion of several candidate genes, we discovered mutations in MECP2, the gene that encodes the transcriptional repressor, methyl-CpG-binding protein 2. Since then, nonsense, missense, or frameshift mutations have been found in at least 80% of girls affected with classic Rett syndrome. Sixty-four percent of mutations are recurrent C > T transitions at eight CpG dinucleotides mutation hotspots, while the C-terminal region of the gene is prone to recurrent multinucleotide deletions (11%). Most mutations are predicted to result in total or partial loss of function of MeCP2. There is no clear correlation between the type and position of the mutation and the phenotypic features of classic and variant Rett syndrome patients, and XCI appears to be a major determinant of phenotypic severity. Further research focuses on the pathogenic consequences of these mutations along the hypothesis of loss of transcriptional repression of a small number of genes that are essential for neuronal function in the maturing brain. MRDD Research Reviews 2002;8:82,86. © 2002 Wiley-Liss, Inc. [source]


Metabolic and haemodynamic effects of metformin in patients with type 2 diabetes mellitus and hypertension

DIABETES OBESITY & METABOLISM, Issue 5 2001
M. H. Uehara
SUMMARY Background Since metformin improves insulin sensitivity, it has been indicated for patients with diabetes and hypertension, which are insulin-resistant conditions. In contrast to its well-known effects on carbohydrate metabolism, its potential for reducing blood pressure (BP) and its effect on leptin levels have been investigated less frequently. Patients and Methods A double-blind, randomized, placebo-controlled trial was carried out with 26 overweight diabetic subjects with mild-to-moderate hypertension to assess the effects of metformin-induced glycaemic control on BP and metabolic parameters. After a 4-week placebo period, when BP was stabilized by calcium channel blockers, they received either metformin (MG) or placebo (PG) for 12 weeks. Results Neither group showed any change in weight throughout the study. Only metformin-treated patients reduced fasting plasma glucose (8.54 + 1.72 to 7.54 + 1.33 mmol/l, p <,0.05), although HbA1c had decreased in both groups (PG: 6.7±3.0 to 5.9±2.6%; MG: 5.3±1.5 to 4.6±0.9%; p <,0.05). The initial office mean BPs were similar and decreased at the end of the treatment period in both groups, reaching statistical significance only in MG (105.7±8.0 to 99.2±9.3 mmHg, p <,0.05). No difference was observed when comparing baseline and final values obtained by 24-h ambulatory BP monitoring. Metformin induced a reduction in both insulinaemia (71.0±62.4 to 38.0±23.0 pmol/l, p <,0.05) and the insulin resistance index (3.5±2.7 to 1.8±1.0, p <,0.05). The two groups had similar baseline leptin levels which remained unchanged after treatment (PG: 16.8±7.9 to 21.4±14.6 ,g/l; MG: 18.5±10.3 to 18.4±8.9 ,g/l). Dopamine levels increased significantly only in metformin-treated subjects. Conclusions Reductions in both the insulin levels and the resistance index reinforced metformin capacity to improve peripheral sensitivity. Moreover, such benefits were not accompanied by any hypotensive effects. Since leptin levels were affected neither by metformin per se nor by the induced insulinaemia reduction, our data support the role of body weight as the major determinant of circulating leptin levels. [source]


Reduced plasma total homocysteine concentrations in Type 1 diabetes mellitus is determined by increased renal clearance

DIABETIC MEDICINE, Issue 3 2005
B. A. J. Veldman
Abstract Introduction Elevated plasma levels of total homocysteine are related to the development of vascular complications. Patients with diabetes mellitus are particularly at risk for the development of these complications. Several factors determine plasma total homocysteine including renal function. Aims As early Type 1 diabetes is characterized by a relative glomerular hyperfiltration, increased renal clearance could contribute to decreased levels of homocysteine as observed in Type 1 diabetes mellitus. Therefore we investigated the relationship between plasma total homocysteine and the glomerular filtration rate (GFR). Methods In 92 Type 1 diabetes patients and 44 control subjects, we measured GFR and effective renal plasma flow (ERPF) by means of continuous infusion of inulin and p-aminohippurate. Fasting plasma total homocysteine was measured using high performance liquid chromatography. Results GFR (121 ± 21 resp. 104 ± 14 ml/min; P < 0.001) and ERPF (563 ± 127 resp. 516 ± 121 ml/min; P = 0.05) were significantly higher in Type 1 diabetes patients as compared with control subjects. Plasma total homocysteine was reduced in Type 1 diabetes patients as compared with control subjects (11.0 ± 4.5 resp. 13.4 ± 7 µmol/l; P = 0.01). Plasma total homocysteine was strongly correlated with GFR (Type 1 diabetes patients: r = ,0.43, P < 0.001; control subjects: r = ,0.39, P = 0.01). Conclusion GFR is a major determinant of plasma total homocysteine levels in Type 1 diabetes patients as well as control subjects. The reduced plasma total homocysteine levels in diabetes patients can be explained by an increased GFR. [source]


In-hospital breast feeding rates among women with gestational diabetes and pregestational Type 2 diabetes in South Auckland

DIABETIC MEDICINE, Issue 2 2005
D. Simmons
Abstract Aim To describe the uptake of breast feeding in mothers with either Type 2 diabetes or gestational diabetes (GDM) in a hospital serving a multiethnic community in South Auckland, New Zealand. Research design and methods A retrospective study of all women attending the Diabetes in Pregnancy clinic over a 4-year period was undertaken: 30 women had Type 2 diabetes and 373 GDM. Results Compared with mothers with GDM, mothers with Type 2 diabetes were less likely to breast feed in any way as the first feed (41.4% vs. 68.0%, P = 0.011) or at discharge (69.0% vs. 84.0%, P = 0.039). In the combined group, there were no differences in uptake of breast feeding by ethnicity, age, parity, body mass index, smoking or antenatal glycaemia, use of insulin or presence of hypertension. Breast feeding on discharge was associated with a higher APGAR score, breast feeding as the first feed (78.2% vs. 19.4%, P < 0.001) and lower rates of delivery by Caesarean section (17.0% vs. 31.8%, P = 0.006). Logistic regression showed breast feeding as the first feed, the major determinant for breast feeding on discharge. Conclusions Factors delaying breast feeding as the first feed are the major determinant of breast feeding on discharge. Strategies to increase breast feeding as the first feed among women with Type 2 diabetes, and those having a Caesarean section, may be useful in increasing the uptake of breast feeding in the longer term. [source]


Gastric emptying in diabetes: clinical significance and treatment

DIABETIC MEDICINE, Issue 3 2002
M. Horowitz
Abstract The outcome of recent studies has led to redefinition of concepts relating to the prevalence, pathogenesis and clinical significance of disordered gastric emptying in patients with diabetes mellitus. The use of scintigraphic techniques has established that gastric emptying is abnormally slow in approx. 30,50% of outpatients with long-standing Type 1 or Type 2 diabetes, although the magnitude of this delay is modest in many cases. Upper gastrointestinal symptoms occur frequently and affect quality of life adversely in patients with diabetes, although the relationship between symptoms and the rate of gastric emptying is weak. Acute changes in blood glucose concentration affect both gastric motor function and upper gastrointestinal symptoms. Gastric emptying is slower during hyperglycaemia when compared with euglycaemia and accelerated during hypoglycaemia. The blood glucose concentration may influence the response to prokinetic drugs. Conversely, the rate of gastric emptying is a major determinant of post-prandial glycaemic excursions in healthy subjects, as well as in Type 1 and Type 2 patients. A number of therapies currently in development are designed to improve post-prandial glycaemic control by modulating the rate of delivery of nutrients to the small intestine. [source]


Geographic body size gradients in tropical regions: water deficit and anuran body size in the Brazilian Cerrado

ECOGRAPHY, Issue 4 2009
Miguel Á. Olalla-Tárraga
A recent interspecific study found Bergmann's size clines for Holarctic anurans and proposed an explanation based on heat balance to account for the pattern. However, this analysis was limited to cold temperate regions, and exploring the patterns in warmer tropical climates may reveal other factors that also influence anuran body size variation. We address this using a Cerrado anuran database. We examine the relationship between mean body size in a grid of 1° cells and environmental predictors and test the relative support for four hypotheses using an AIC-based model selection approach. Also, we considered three different amphibian phylogenies to partition the phylogenetic and specific components of the interspecific variation in body size using a method analogous to phylogenetic eigen vector regression (PVR). To consider the potential effects of spatial autocorrelation we use eigenvector-based spatial filters. We found the largest species inhabiting high water deficit areas in the northeast and the smallest in the wet southwest. Our results are consistent with the water availability hypothesis which, coupled with previous findings, suggests that the major determinant of interspecific body size variation in anurans switches from energy to water towards the equator. We propose that anuran body size gradients reflect effects of reduced surface to volume ratios in larger species to control both heat and water balance. [source]


Spatial utilisation of fast-ice by Weddell seals Leptonychotes weddelli during winter

ECOGRAPHY, Issue 3 2005
Samantha Lake
This study describes the distribution of Weddell seals Leptonychotes weddelli in winter (May,September 1999) at the Vestfold Hills, in Prydz Bay, East Antarctica. Specifically, we describe the spatial extent of haul-out sites in shore,fast sea-ice, commonly referred to as fast-ice. As winter progressed, and the fast-ice grew thick (ca 2 m), most of the inshore holes closed over, and the seals' distribution became restricted to ocean areas beyond land and islands. Using observations from the end of winter only, we fitted Generalised Additive Models (GAMs) to generate resource selection functions, which are models that yield values proportional to the probability of use. The models showed that seal distribution was defined mainly by distance to ice-edge and distance to land. Distance to ice-bergs was also selected for models of some regions. We present the results as maps of the fitted probability of seal presence, predicted by the binomial GAM for offshore regions, both with and without autocorrelation terms. The maps illustrate the expected distribution encompassing most of the observed distribution. On this basis, we hypothesise that propensity for the fast-ice to crack is the major determinant of Weddell seal distribution in winter. Proximity to open water and pack-ice habitats could also influence the distribution of haul-out sites in fast-ice areas. This is the first quantitative study of Weddell seal distribution in winter. Potential for regional variation is discussed. [source]


Oxidative stress as a mediator of life history trade-offs: mechanisms, measurements and interpretation

ECOLOGY LETTERS, Issue 1 2009
Pat Monaghan
Abstract The concept of trade-offs is central to our understanding of life-history evolution. The underlying mechanisms, however, have been little studied. Oxidative stress results from a mismatch between the production of damaging reactive oxygen species (ROS) and the organism's capacity to mitigate their damaging effects. Managing oxidative stress is likely to be a major determinant of life histories, as virtually all activities generate ROS. There is a recent burgeoning of interest in how oxidative stress is related to different components of animal performance. The emphasis to date has been on immediate or short-term effects, but there is an increasing realization that oxidative stress will influence life histories over longer time scales. The concept of oxidative stress is currently used somewhat loosely by many ecologists, and the erroneous assumption often made that dietary antioxidants are necessarily the major line of defence against ROS-induced damage. We summarize current knowledge on how oxidative stress occurs and the different methods for measuring it, and highlight where ecologists can be too simplistic in their approach. We critically review the potential role of oxidative stress in mediating life-history trade-offs, and present a framework for formulating appropriate hypotheses and guiding experimental design. We indicate throughout potentially fruitful areas for further research. [source]


Total population density during the first year of life as a major determinant of lifetime body-length trajectory in marble trout

ECOLOGY OF FRESHWATER FISH, Issue 4 2008
S. Vincenzi
Abstract,,, The conditions experienced early in life can strongly influence life-history trajectories in a variety of animal species. Here, we use data from four isolated populations of the endangered stream-dwelling salmonid marble trout (Salmo marmoratus Cuvier 1817) living in the Soca and Idrijca river basins (Slovenia) to explore the influence of the total density experienced during and after the first year of life by marble trout year-classes on body length of marble trout through the lifetime. Analyses were performed by pooling together the stream-specific datasets to cover a wider range of densities. Mean body length of marble trout year-classes through the lifetime (from age 1+ to 5+) was negatively related to total density of marble trout during the first year of life. The relationship between density during the first growth period and body length through the lifetime was well described by negative power curves. Total population density after the first year of life was not correlated with body length, thus suggesting that body growth trajectories are heavily determined early in life. Given size-dependent sexual maturity and egg production in marble trout, the relationship between density early in life and lifetime individual growth may have strong implications in terms of population dynamics and regulation of population size. [source]


Early survival of marble trout Salmo marmoratus: evidence for density dependence?

ECOLOGY OF FRESHWATER FISH, Issue 2 2007
S. Vincenzi
Abstract,,, The role of endogenous and exogenous factors in regulating population dynamics of freshwater salmonids is still a matter of debate. The aim of the present work was to assess the relative importance of density-dependent and -independent factors in determining the survival of marble trout (Salmo marmoratus) yearlings in two populations living in Slovenian streams (Zakojska and Gorska). The investigation was performed by combining a classical life table analysis with Monte Carlo simulation. Size-dependent fecundity was estimated by stripping wild adults in the fish farm. A significant positive relationship was found between length of marble trout females and the number of eggs produced. Egg density was the major determinant of survival from eggs to age 1+ (,0) in both streams. Residuals of the relationship between ,0 and egg density were positively correlated with rainfall only in Zakojska, probably because, within a certain range, more intense rainfalls increases stream flow and, consequently, suitable habitat for trout. Our study shows how density-dependent and environmental factors can interact to determine the survival of marble trout during the first year of life. [source]


State Policy, Economic Crisis, Gender, and Family Ties: Determinants of Family Remittances to Cuba

ECONOMIC GEOGRAPHY, Issue 1 2004
Sarah A. Blue
Abstract: This article advances the argument that changing economic conditions in the home country act as an important determinant for sending remittances. Research on the determinants of remittances has tended to focus on the characteristics of the sending population. In the case of Cuba, disproportionate attention is paid to political disincentives to send remittances and not enough to changing state policy and the growing economic demand for remittances in that country. Using empirical data gathered from households in Havana, this article tests the importance of economic conditions in the home country, political ideology, the relationship of the sender to the receiver, the length of time away from home, and gender as determinants for remittances. Migration during an economic crisis, having immediate relatives in the home country, and female gender positively influenced remittance behavior for Cuban emigrants. Visits to the home country, especially for migrants who had left decades earlier, were found to be critical for reestablishing family connections and increasing remittances. No support was found for political disincentives as a major determinant of remittance sending to Cuba. [source]


Proximate Determinants of Reproductive Skew in Polygyne Colonies of the Ant Formica fusca

ETHOLOGY, Issue 11 2002
Minttumaaria Hannonen
Understanding the determinants of reproductive skew (the partitioning of reproduction among co-breeding individuals) is one of the major questions in social evolution. In ants, multiple-queen nests are common and reproductive skew among queens has been shown to vary tremendously both within and between species. Proximate determinants of skew may be related to both queen and worker behaviour. Queens may attempt to change their reproductive share through dominance interactions, egg eating and by changing individual fecundity. Conversely, workers are in a position to regulate the reproductive output of queens when rearing the brood. This paper investigates queen behaviour at the onset of egg laying and the effect of queen fecundity and worker behaviour on brood development and reproductive shares of multiple queens in the ant Formica fusca. The study was conducted in two-queen laboratory colonies where the queens produced only worker offspring. The results show that in this species reproductive apportionment among queens is not based on dominance behaviour and aggression, but rather on differences in queen fecundity. We also show that, although the queen fecundity at the onset of brood rearing is a good indicator of her final reproductive output, changes in brood composition occur during brood development. Our results highlight the importance of queen fecundity as a major determinant of her reproductive success. They furthermore suggest that in highly derived polygyne species, such as the Formica ants, direct interactions as a means for gaining reproductive dominance have lost their importance. [source]


CD8+ T-cell responses to Theileria parva are preferentially directed to a single dominant antigen: Implications for parasite strain-specific immunity

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2009
Niall D. MacHugh
Abstract Although immunodominance of CD8+ T-cell responses is a well-recognised feature of viral infections, its role in responses to more antigenically complex pathogens is less clear. In previous studies we have observed that CD8+ T-cell responses to Theileria parva exhibit different patterns of parasite strain specificity in cattle of different MHC genotypes. In the current study, we demonstrated that animals homozygous for the A10 and A18 MHC haplotypes have detectable responses to only one of 5 T. parva antigens. Over 60% of the responding T cells from the A18+ and A10+ animals recognised defined epitopes in the Tp1 and Tp2 antigens, respectively. Comparison of T-cell receptor , chain expression profiles of CD8+ T-cell lines and CD8+ T cells harvested ex vivo confirmed that the composition of the T-cell lines was representative of the in vivo memory CD8+ T-cell populations. Analysis of the Tp1 and Tp2 antigens revealed sequence polymorphism, which was reflected by differential recognition by T-cell lines. In conclusion, we have demonstrated a profound immunodominance in the CD8+ T-cell response to T. parva, which we propose is a major determinant of the parasite strain specificity of the response and hence immune protection. [source]


EFNS guidelines on cognitive rehabilitation: report of an EFNS task force

EUROPEAN JOURNAL OF NEUROLOGY, Issue 9 2005
Members of the Task Force on Cognitive Rehabilitation
Disorders of language, spatial perception, attention, memory, calculation and praxis are a frequent consequence of acquired brain damage [in particular, stroke and traumatic brain injury (TBI)] and a major determinant of disability. The rehabilitation of aphasia and, more recently, of other cognitive disorders is an important area of neurological rehabilitation. We report here a review of the available evidence about effectiveness of cognitive rehabilitation. Given the limited number and generally low quality of randomized clinical trials (RCTs) in this area of therapeutic intervention, the Task Force considered, besides the available Cochrane reviews, evidence of lower classes which was critically analysed until a consensus was reached. In particular, we considered evidence from small group or single cases studies including an appropriate statistical evaluation of effect sizes. The general conclusion is that there is evidence to award a grade A, B or C recommendation to some forms of cognitive rehabilitation in patients with neuropsychological deficits in the post-acute stage after a focal brain lesion (stroke, TBI). These include aphasia therapy, rehabilitation of unilateral spatial neglect (ULN), attentional training in the post-acute stage after TBI, the use of electronic memory aids in memory disorders, and the treatment of apraxia with compensatory strategies. There is clearly a need for adequately designed studies in this area, which should take into account specific problems such as patient heterogeneity and treatment standardization. [source]


Somatodendritic autoreceptor regulation of serotonergic neurons: dependence on l -tryptophan and tryptophan hydroxylase-activating kinases

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2005
Rong-Jian Liu
Abstract The somatodendritic 5-HT1A autoreceptor has been considered a major determinant of the output of the serotonin (5-HT) neuronal system. However, recent studies in brain slices from the dorsal raphe nucleus have questioned the relevance of 5-HT autoinhibition under physiological conditions. In the present study, we found that the difficulty in demonstrating 5-HT tonic autoinhibition in slice results from in vitro conditions that are unfavorable for sustaining 5-HT synthesis. Robust, tonic 5-HT1A autoinhibition can be restored by reinstating in vivo 5-HT synthesizing conditions with the initial 5-HT precursor l -tryptophan and the tryptophan hydroxylase co-factor tetrahydrobiopterin (BH4). The presence of tonic autoinhibition under these conditions was revealed by the disinhibitory effect of a low concentration of the 5-HT1A antagonist WAY 100635. Neurons showing an autoinhibitory response to l -tryptophan were confirmed immunohistochemically to be serotonergic. Once conditions for tonic autoinhibition had been established in raphe slice, we were able to show that 5-HT autoinhibition is critically regulated by the tryptophan hydroxylase-activating kinases calcium/calmodulin protein kinase II (CaMKII) and protein kinase A (PKA). In addition, at physiological concentrations of l -tryptophan, there was an augmentation of 5-HT1A receptor-mediated autoinhibition when the firing of 5-HT cells activated with increasing concentrations of the ,1 adrenoceptor agonist phenylephrine. Increased calcium influx at higher firing rates, by activating tryptophan hydroxylase via CaMKII and PKA, can work together with tryptophan to enhance negative feedback control of the output of the serotonergic system. [source]


Increase in the fracture toughness and bond energy of clay by a root exudate

EUROPEAN JOURNAL OF SOIL SCIENCE, Issue 5 2008
B. Zhang
Summary Root exudates help drive the formation of the rhizosphere by binding soil particles, but the underlying physical mechanisms have not been quantified. This was addressed by measuring the impact of a major component of root exudates, polygalacturonic acid (PGA), on the interparticle bond energy and fracture toughness of clay. Pure kaolinite was mixed with 0, 1.2, 2.4, 4.9 or 12.2 g PGA kg,1 to form test specimens. Half of the specimens were washed repeatedly to remove unbound PGA and evaluate the persistence of the effects, similar to weathering in natural soils. Fracture toughness, KIC, increased exponentially with added PGA, with washing increasing this trend. In unwashed specimens KIC ranged from 54.3 ± 2.5 kPa m,1/2 for 0 g PGA kg,1 to 86.9 ± 4.7 kPa m,1/2 for 12.2 g PGA kg,1. Washing increased KIC to 61.3 ± 1.2 kPa m,1/2 for 0 g PGA kg,1 and 132.1 ± 4.9 kPa m,1/2 for 12.2 g PGA kg,1. The apparent bond energy, ,, of the fracture surface increased from 5.9 ± 0.6 J m,2 for 0 g kg,1 to 12.0 ± 1.1 J m,2 for 12.2 g kg,1 PGA in the unwashed specimens. The washed specimens had , of 13.0 ± 1.9 J m,2 for 0 g kg,1 and 21.3 ± 2.6 J m,2 for 12.2 g PGA kg,1. Thus PGA, a major component of root exudates, has a large impact on the fracture toughness and bond energy of clay, and is likely to be a major determinant in the formation of the rhizosphere. This quantification of the thermodynamics of fracture will be useful for modelling rhizosphere formation and stability. [source]


Regulation of MC1R signalling by G-protein-coupled receptor kinases

EXPERIMENTAL DERMATOLOGY, Issue 9 2004
J. C. García-Borrón
The melanocortin 1 receptor (MC1R) is a key regulator of melanocyte proliferation and differentiation and a major determinant of human skin phototype and skin cancer risk. Although the regulation of MC1R gene expression is fairly well understood, little is known about regulatory mechanisms acting at the protein level. In particular, no information is available on homologous desensitization of MC1R signalling. We studied MC1R and Mc1r desensitization and found that: 1) MC1R and Mc1r in melanoma cells undergo homologous desensitization, demonstrated by decreases in cAMP contents upon continuous exposure to agonists, 2) desensitization is not dependent on PKA, PKC, calcium mobilization or MAPKs but is agonist dose dependent, suggesting a role of receptor occupancy, 3) melanoma cells express two members of the GRK family of serine/threonine kinases, GRK2 and GRK6, 4. These kinases are expressed in normal melanocytes, 5) in cotransfection experiments performed with HEK 293T cells, GRK2 strongly impairs agonist-dependent signalling by MC1R or Mc1r, 6) expression of a dominant negative GRK2 mutant in melanoma cells increases their cAMP response to MC1R agonists, 7) cotransfection of HEK 293T cells with GRK6 and MC1R inhibits both basal and agonist-dependent signalling, and 8) cAMP production in agonist-stimulated melanoma cells is strongly impaired by enrichment with GRK6 following stable transfection. Therefore, GRK2 and GRK6 are key regulators of MC1R signalling and may be important determinants of normal and pathological skin pigmentation. [source]


The molecular determinants of sunburn cell formation

EXPERIMENTAL DERMATOLOGY, Issue 3 2001
G. Murphy
Abstract: Sunburn cell (SBC) formation in the epidermis is a characteristic consequence of ultraviolet radiation (UVR) exposure at doses around or above the minimum erythema dose. SBC have been identified morphologically and biologically as keratinocytes undergoing apoptosis. There is evidence that SBC formation is a protective mechanism to eliminate cells at risk of malignant transformation. The level of DNA photodamage is a major determinant of SBC induction by a process controlled by the tumor suppressor gene p53. However, extra-nuclear events also contribute to SBC formation, such as the activation of death receptors including CD95/Fas. UVR triggers death receptors either by direct activation of these surface molecules or by inducing the release of their ligands such as CD95 ligand or tumor necrosis factor. Oxidative stress also appears to be involved, probably via mitochondrial pathways, resulting in the release of cytochrome C. Pathways which modify SBC formation are now extensively studied given the importance of apoptosis in eliminating irreparably damaged cells. A greater understanding of the mechanisms that induce and prevent UVR-induced apoptosis will contribute to our understanding of mechanisms relevant in genomic integrity. [source]


Comparison of the firing patterns of human postganglionic sympathetic neurones and spinal , motoneurones during brief bursts

EXPERIMENTAL PHYSIOLOGY, Issue 1 2004
Vaughan G. Macefield
Focal recordings from individual postganglionic sympathetic neurones in awake human subjects have revealed common firing properties. One of the most striking features is that they tend to fire only once per sympathetic burst. Why this should be so is not known, but we propose that the short duration of the burst may limit the number of times a sympathetic neurone can fire. Indeed, while the normal variation in cardiac interval and burst duration is too narrow to reveal a correlation between burst duration and the number of spikes generated, we know that spike generation is doubled when burst duration is doubled following ectopic heart beats. To test the hypothesis that the burst duration constrains the firing of individual sympathetic neurones to one per burst, we used the human skeletomotor system as a model for the sympathetic nervous system, which allowed us to vary burst duration and amplitude experimentally. Intramuscular recordings were made from 27 single motor units (, motoneurones) in the tibialis anterior or soleus muscles of seven subjects; multiunit EMG activity was recorded via surface electrodes and blood pressure was recorded continuously. Subjects were instructed to generate EMG bursts of varying amplitude in the intervals between heart beats. By constraining the firing of , motoneurones to brief (,400 ms) bursts we could emulate real sympathetic bursts. Individual motoneurones generated 0,7 spikes during the emulated sympathetic bursts, with firing patterns similar to those exhibited by real sympathetic neurones. Eleven motor units showed significant positive linear correlations between the number of spikes they generated within a burst and its amplitude, whereas for 17 motor units there were significant positive correlations between the number of spikes and burst duration. This indicates that burst duration is a major determinant of the number of times an , motoneurone will fire during a brief burst, and we suggest that the same principle may explain the firing pattern typical of human sympathetic neurones. [source]


Loss-of-function variants of the human melanocortin-1 receptor gene in melanoma cells define structural determinants of receptor function

FEBS JOURNAL, Issue 24 2002
Jesús Sánchez Más
The ,-melanocyte-stimulating hormone (,MSH) receptor (MC1R) is a major determinant of mammalian skin and hair pigmentation. Binding of ,MSH to MC1R in human melanocytes stimulates cell proliferation and synthesis of photoprotective eumelanin pigments. Certain MC1R alleles have been associated with increased risk of melanoma. This can be theoretically considered on two grounds. First, gain-of-function mutations may stimulate proliferation, thus promoting dysplastic lesions. Second, and opposite, loss-of-function mutations may decrease eumelanin contents, and impair protection against the carcinogenic effects of UV light, thus predisposing to skin cancers. To test these possibilities, we sequenced the MC1R gene from seven human melanoma cell (HMC) lines and three giant congenital nevus cell (GCNC) cultures. Four HMC lines and two GCNC cultures contained MC1R allelic variants. These were the known loss-of-function Arg142His and Arg151Cys alleles and a new variant, Leu93Arg. Moreover, impaired response to a superpotent ,MSH analog was demonstrated for the cell line carrying the Leu93Arg allele and for a HMC line homozygous for wild-type MC1R. Functional analysis in heterologous cells stably or transiently expressing this variant demonstrated that Leu93Arg is a loss-of-function mutation abolishing agonist binding. These results, together with site-directed mutagenesis of the vicinal Glu94, demonstrate that the MC1R second transmembrane fragment is critical for agonist binding and maintenance of a resting conformation, whereas the second intracellular loop is essential for coupling to the cAMP system. Therefore, loss-of-function, but not activating MC1R mutations are common in HMC. Their study provides important clues to understand MC1R structure-function relationships. [source]


Effect of sequence polymorphism and drug resistance on two HIV-1 Gag processing sites

FEBS JOURNAL, Issue 16 2002
Anita Fehér
The HIV-1 proteinase (PR) has proved to be a good target for antiretroviral therapy of AIDS, and various PR inhibitors are now in clinical use. However, there is a rapid selection of viral variants bearing mutations in the proteinase that are resistant to clinical inhibitors. Drug resistance also involves mutations of the nucleocapsid/p1 and p1/p6 cleavage sites of Gag, both in vitro and in vivo. Cleavages at these sites have been shown to be rate limiting steps for polyprotein processing and viral maturation. Furthermore, these sites show significant sequence polymorphism, which also may have an impact on virion infectivity. We have studied the hydrolysis of oligopeptides representing these cleavage sites with representative mutations found as natural variations or that arise as resistant mutations. Wild-type and five drug resistant PRs with mutations within or outside the substrate binding site were tested. While the natural variations showed either increased or decreased susceptibility of peptides toward the proteinases, the resistant mutations always had a beneficial effect on catalytic efficiency. Comparison of the specificity changes obtained for the various substrates suggested that the maximization of the van der Waals contacts between substrate and PR is the major determinant of specificity: the same effect is crucial for inhibitor potency. The natural nucleocapsid/p1 and p1/p6 sites do not appear to be optimized for rapid hydrolysis. Hence, mutation of these rate limiting cleavage sites can partly compensate for the reduced catalytic activity of drug resistant mutant HIV-1 proteinases. [source]


When fathers make the difference: efficacy of male sexually selected antimicrobial glands in enhancing fish hatching success

FUNCTIONAL ECOLOGY, Issue 1 2010
Matteo Pizzolon
Summary 1.,Egg and offspring resistance to pathogens is a major determinant of survival and has been mainly ascribed to maternal factors. However, paternal production of antimicrobials was recently suggested to increase offspring survival in species where males perform egg care. 2.,In the peacock blenny, Salaria pavo, a demersal spawning species where males exhibit a pair of anal glands producing lysozyme-like compounds, we tested the antimicrobial activity and the egg protection efficacy of these glands. The anal gland secretion (AGS) has an inhibitory effect on the growth of both Gram-negative and Gram-positive bacteria, including those causing the most severe fish diseases in marine culture. The egg clutches cared for by males deprived of anal glands have a significantly lower survival rate than those cared for by sham-operated males and non-viable eggs showed clear signs of bacterial infection. 3.,Anal gland secretion production and its protein content are proportional to gland size. In species where male parental care plays a crucial role in offspring survival, females are expected to assess mates selecting those traits that are reliably associated with parental ability. Hence, we experimentally challenged females with dummy males differing in anal gland size. Females definitely preferred dummy males with larger anal glands, suggesting that their choice is driven by the pursuit of direct fecundity benefits. 4.,These findings indicate that antimicrobial production is a crucial component of male parental care. The contribution of antimicrobials to male performance as fathers suggests that the development of traits devoted to this function may influence male attractiveness and be sexually selected. [source]


How Much Is Postacute Care Use Affected by Its Availability?

HEALTH SERVICES RESEARCH, Issue 2 2005
Melinda Beeuwkes Buntin
Objective. To assess the relative impact of clinical factors versus nonclinical factors,such as postacute care (PAC) supply,in determining whether patients receive care from skilled nursing facilities (SNFs) or inpatient rehabilitation facilities (IRFs) after discharge from acute care. Data Sources and Study Setting. Medicare acute hospital, IRF, and SNF claims provided data on PAC choices; predictors of site of PAC chosen were generated from Medicare claims, provider of services, enrollment file, and Area Resource File data. Study Design. We used multinomial logit models to predict PAC use by elderly patients after hospitalizations for stroke, hip fractures, or lower extremity joint replacements. Data Collection/Extraction Methods. A file was constructed linking acute and postacute utilization data for all medicare patients hospitalized in 1999. Principal Findings. PAC availability is a more powerful predictor of PAC use than the clinical characteristics in many of our models. The effects of distance to providers and supply of providers are particularly clear in the choice between IRF and SNF care. The farther away the nearest IRF is, and the closer the nearest SNF is, the less likely a patient is to go to an IRF. Similarly, the fewer IRFs, and the more SNFs, there are in the patient's area the less likely the patient is to go to an IRF. In addition, if the hospital from which the patient is discharged has a related IRF or a related SNF the patient is more likely to go there. Conclusions. We find that the availability of PAC is a major determinant of whether patients use such care and which type of PAC facility they use. Further research is needed in order to evaluate whether these findings indicate that a greater supply of PAC leads to both higher use of institutional care and better outcomes,or whether it leads to unwarranted expenditures of resources and delays in returning patients to their homes. [source]


Nonobese population in a developing country has a high prevalence of nonalcoholic fatty liver and significant liver disease,,

HEPATOLOGY, Issue 5 2010
Kausik Das
There is a paucity of community-based epidemiological data on nonalcoholic fatty liver (NAFL) among nonaffluent populations in developing countries. Available studies are radiological and/or biochemical and lack histological assessment, limiting their strength. We conducted a prospective epidemiological study comprising a 1:3 subsample of all adult (>18 years) inhabitants of a rural administrative unit of West Bengal, India. Subjects positive for hepatitis B virus and/or hepatitis C virus infection and consuming any amount of alcohol were excluded. Diagnosis of NAFL was by dual radiological screening protocol consisting of ultrasonographic and computed tomographic examination of the liver. Transient elastographic examination and liver biopsy were performed in a subset to identify significant liver disease. The risk factors of having NAFL were analyzed. A total of 1,911 individuals were analyzed, 7% of whom were overweight and 11% of whom had abdominal obesity. The prevalence of NAFL, NAFL with elevated alanine aminotransferase, and cryptogenic cirrhosis was 8.7%, 2.3%, and 0.2%, respectively. Seventy-five percent of NAFL subjects had a body mass index (BMI) <25 kg/m2, and 54% were neither overweight nor had abdominal obesity. The subjects with the highest risk of having NAFL were those with a BMI >25 kg/m2 (odds ratio 4.3, 95% confidence interval 1.6-11.5). Abdominal obesity, dysglycemia (fasting plasma glucose >100 mg/dL or elevated homeostatic model assessment of insulin resistance), and higher income were the other risk factors. Even having a normal BMI (18.5-24.9 kg/m2) was associated with a 2-fold increased risk of NAFL versus those with a BMI <18.5 kg/m2. Conclusion: There is a significant prevalence of NAFL and potentially significant liver disease, including cryptogenic cirrhosis, in this predominantly nonobese, nonaffluent population in a developing country. NAFL will be a major determinant of future liver disease burden in countries of the developing world. (HEPATOLOGY 2010) [source]