Overwhelming Evidence (overwhelming + evidence)

Distribution by Scientific Domains

Selected Abstracts

Candidate genes and the behavioral phenotype in 22q11.2 deletion syndrome

Sarah E. Prasad
Abstract There is an overwhelming evidence that children and adults with 22q11.2 deletion syndrome (22q11.2DS) have a characteristic behavioral phenotype. In particular, there is a growing body of evidence that indicates an unequivocal association between 22q11.2DS and schizophrenia, especially in adulthood. Deletion of 22q11.2 is the third highest risk for the development of schizophrenia, with only a greater risk conferred by being the child of two parents with schizophrenia or the monozygotic co-twin of an affected individual. Both linkage and association studies of people with schizophrenia have implicated several susceptibility genes, of which three are in the 22q11.2 region; catechol- o -methyltransferase (COMT), proline dehydrogenase (PRODH), and Gnb1L. In addition, variation in Gnb1L is associated with the presence of psychosis in males with 22q11.2DS. In mouse models of 22q11.2DS, haploinsufficiency of Tbx1 and Gnb1L is associated with reduced prepulse inhibition, a schizophrenia endophenotype. The study of 22q11.2DS provides an attractive model to increase our understanding of the development and pathogenesis of schizophrenia and other psychiatric disorders in 22q11.2DS and in wider population. © 2008 Wiley-Liss, Inc. Dev Disabil Res Rev 2008;14:26,34. [source]

Protein kinase C and the development of diabetic vascular complications

K. J. Way
Abstract Hyperglycemic control in diabetes is key to preventing the development and progression of vascular complications such as retinopathy, nephropathy and neuropathy. Increased activation of the diacylglycerol (DAG)-protein kinase C (PKC) signal transduction pathway has been identified in vascular tissues from diabetic animals, and in vascular cells exposed to elevated glucose. Vascular abnormalities associated with glucose-induced PKC activation leading to increased synthesis of DAG include altered vascular blood flow, extracellular matrix deposition, basement membrane thickening, increased permeability and neovascularization. Preferential activation of the PKC, isoform by elevated glucose is reported to occur in a variety of vascular tissues. This has lead to the development of LY333531, a PKC, isoform specific inhibitor, which has shown potential in animal models to be an orally effective and nontoxic therapy able to produce significant improvements in diabetic retinopathy, nephropathy, neuropathy and cardiac dysfunction. Additionally, the antioxidant vitamin E has been identified as an inhibitor of the DAG-PKC pathway, and shows promise in reducing vascular complications in animal models of diabetes. Given the overwhelming evidence indicating a role for PKC activation in contributing to the development of diabetic vascular complications, pharmacological therapies that can modulate this pathway, particularly with PKC isoform selectivity, show great promise for treatment of vascular complications, even in the presence of hyperglycemia. Diabet. Med. 18, 945,959 (2001) [source]

The use of leukocyte profiles to measure stress in vertebrates: a review for ecologists

A. K. Davis
Summary 1A growing number of ecologists are turning to the enumeration of white blood cells from blood smears (leukocyte profiles) to assess stress in animals. There has been some inconsistency and controversy in the ecological literature, however, regarding their interpretation. The inconsistencies may stem partly from a lack of information regarding how stress affects leukocytes in different taxa, and partly from a failure on the part of researchers in one discipline to consult potentially informative literature from another. 2Here, we seek to address both issues by reviewing the literature on the leukocyte response to stress, spanning the taxa of mammals (including humans), birds, amphibians, reptiles and fish. 3We show that much of the early literature points to a close link between leukocyte profiles and glucocorticoid levels. Specifically, these hormones act to increase the number and percentage of neutrophils (heterophils in birds and reptiles), while decreasing the number and percentage of lymphocytes. This phenomenon is seen in all five vertebrate taxa in response to either natural stressors or exogenous administration of stress hormones. For the ecologist, therefore, high ratios of heterophils or neutrophils to lymphocytes (,H : L' or ,N : L' ratios) in blood samples reliably indicate high glucocorticoid levels. Furthermore, this close relationship between stress hormones and N : L or H : L ratios needs to be highlighted more prominently in haematological assessments of stress, as it aids the interpretation of results. 4As with hormone assays, there are challenges to overcome in the use of leukocytes profiles to assess levels of stress; however, there are also advantages to this approach, and we outline each. Given the universal and consistent nature of the haematological response to stress, plus the overwhelming evidence from the veterinary, biomedical and ecological literature reviewed here, we conclude that this method can provide a reliable assessment of stress in all vertebrate taxa. [source]

Reciprocal phenotypic plasticity can lead to stable predator,prey interaction

Akihiko Mougi
Summary 1.,Inducible defences of prey and inducible offences of predators are prevalent strategies in trophic interactions with temporal variation. Due to the inducible properties of the functional traits themselves, which drive the dynamic predator,prey relationship on an ecological time-scale, predator and prey may reciprocally interact through their inducible traits (i.e. reciprocal phenotypic plasticity). 2.,Although overwhelming evidence of the stabilizing effect of inducible traits in either species on community dynamics forcefully suggests a critical ecological role for reciprocal plasticity in predator,prey population dynamics, our understanding of its ecological consequences is very limited. 3.,Within a mathematical modelling framework, we investigated how reciprocal plasticity influences the stability of predator,prey systems. 4.,By assuming two types of phenotypic shift, a density-dependent shift and an adaptive phenotypic shift, we examined two interaction scenarios with reciprocal plasticity: (i) an arms-race-like relationship, in which the defensive prey phenotype is more protective against both predator phenotypes (i.e. normal and offensive) than the normal prey phenotype, and the offensive predator is a more efficient consumer, preying upon both prey phenotypes (i.e. normal and defensive), than the normal predator and (ii) a matching response-like relationship, in which the offensive predator consumes more defensive prey and fewer normal prey than the normal predator. 5.,Results of both phenotypic shift models consistently suggest that given the used set of parameter values, the arms-race-like reciprocal plasticity scenario has the largest stability area, when compared with the other scenarios. In particular, higher stability is achieved when the prey exhibits a high-performance inducible defence. Furthermore, this stabilization is so strong that the destabilizing effects of enrichment may be eliminated, even though the higher flexibility of plasticity does not always stabilize a system. 6.,Recent empirical studies support our model predictions. Clear-cut examples of reciprocal phenotypic plasticity show an arms-race-like relationship in which prey species exhibit induced high-performance defences. We may need to re-examine reported predator,prey interactions in which predator or prey exhibits inducible plasticity to determine whether arms-race-like reciprocal plasticity is a general ecological phenomenon. [source]

Orthotopic Cardiac Transplantation: Comparison of Outcome Using Biatrial, Bicaval, and Total Techniques

Jeffrey A. Morgan M.D.
More recently, however, bicaval and total techniques have been devised in an attempt to improve cardiac anatomy, physiology, and postoperative outcome. A bicaval approach preserves the donor atria and combines the standard left atrial anastomosis with a separate bicaval anastomosis. Total orthotopic heart transplantation involves complete excision of the recipient atria with separate bicaval end-to-end anastomoses, as well as pulmonary venous anastomoses. The aim of this study was to conduct a literature review of studies that compared the three surgical techniques (biatrial, bicaval, and total) for performing orthotopic cardiac transplantation. Numerous outcome variables were evaluated, and included post-transplant survival, atrial dimensions, atrioventricular valvular insufficiency, arrhythmias, pacing requirements, vasopressor requirements, and hospital stay. Methods: We conducted a Medline (Pubmed) search using the terms "biatrial and cardiac transplantation,""bicaval and cardiac transplantation," and "total technique and cardiac transplantation," which yielded 192 entries: 39 of these were studies that compared surgical techniques and were included in the review. Results: There was overwhelming evidence that the bicaval technique provided anatomic and functional advantages, with improvements in post-transplant survival, atrial geometry, and hemodynamics, as well as decreased valvular insufficiency, arrhythmias, pacing requirements, vasopressor requirements, and hospital stay. Conclusions: The bicaval technique was superior to both biatrial and total techniques for numerous outcome variables. To further elucidate this issue, a prospective randomized trial comparing the three techniques, with long-term follow-up, is warranted. [source]

Sarcolemmal and mitochondrial KATP channels and myocardial ischemic preconditioning

J. N. Peart
Abstract Ischemic preconditioning (IPC) is the phenomenon whereby brief periods of ischemia have been shown to protect the myocardium against a sustained ischemic insult. The result of IPC may be manifest as a marked reduction in infarct size, myocardial stunning, or incidence of arrhythmias. While many substances and pathways have been proposed to play a role in the signal transduction mediating the cardioprotective effect of IPC, overwhelming evidence indicates an intimate involvement of the ATP-sensitive potassium channel (KATP channel) in this process. Initial hypotheses suggested that the surface or sarcolemmal KATP (sarcKATP) channel mediated the cardioprotective effects of IPC. However, much research has subsequently supported a major role for the mitochondrial KATP channel (mitoKATP) as the one involved in IPC-mediated cardioprotection. This review presents evidence to support a role for the sarcKATP or the mitoKATP channel as either triggers and/or downstream mediators in the phenomenon of IPC. [source]

Inbred women in a small and isolated Swiss village have fewer children

Abstract Despite overwhelming evidence for a negative effect of inbreeding on fitness in plants and nonhuman animals, the exact nature of its effect in humans remains subject to debate. To obtain a better understanding of the effects of inbreeding on reproductive success in humans, we reconstructed the genealogies of the current inhabitants of a small and isolated Swiss village and used these to estimate the level of inbreeding of both members of all married couples, as well as their relatedness (i.e. the level of inbreeding of their offspring). Although there was no effect of parental relatedness on the number of children a couple had, we found that inbred mothers, but not inbred fathers, had significantly fewer children. Thus, although related couples did not have fewer children themselves, their inbred daughters did leave them with fewer grandchildren. Thereby, we provide evidence for the existence of inbreeding depression in human fertility, also in relatively outbred and egalitarian communities. [source]

Molecular and Cellular Events in Alcohol-Induced Muscle Disease

ALCOHOLISM, Issue 12 2007
Joaquim Fernandez-Solà
Alcohol consumption induces a dose-dependent noxious effect on skeletal muscle, leading to progressive functional and structural damage of myocytes, with concomitant reductions in lean body mass. Nearly half of high-dose chronic alcohol consumers develop alcoholic skeletal myopathy. The pathogenic mechanisms that lie between alcohol intake and loss of muscle tissue involve multiple pathways, making the elucidation of the disease somewhat difficult. This review discusses the recent advances in basic and clinical research on the molecular and cellular events involved in the development of alcohol-induced muscle disease. The main areas of recent research interest on this field are as follows: (i) molecular mechanisms in alcohol exposed muscle in the rat model; (ii) gene expression changes in alcohol exposed muscle; (iii) the role of trace elements and oxidative stress in alcoholic myopathy; and (iv) the role of apoptosis and preapoptotic pathways in alcoholic myopathy. These aforementioned areas are crucial in understanding the pathogenesis of this disease. For example, there is overwhelming evidence that both chronic alcohol ingestion and acute alcohol intoxication impair the rate of protein synthesis of myofibrillar proteins, in particular, under both postabsorptive and postprandial conditions. Perturbations in gene expression are contributory factors to the development of alcoholic myopathy, as ethanol-induced alterations are detected in over 400 genes and the protein profile (i.e., the proteome) of muscle is also affected. There is supportive evidence that oxidative damage is involved in the pathogenesis of alcoholic myopathy. Increased lipid peroxidation is related to muscle fibre atrophy, and reduced serum levels of some antioxidants may be related to loss of muscle mass and muscle strength. Finally, ethanol induces skeletal muscle apoptosis and increases both pro- and antiapoptotic regulatory mechanisms. [source]

Review article: should we kill or should we save Helicobacter pylori?

R.H. Hunt
Results from epidemiological studies and therapeutic clinical trials have shown that Helicobacter pylori infection causes acute and chronic active gastritis and is the initiating factor for the majority of peptic ulcer disease. Eradication of the infection with antibiotics resolves gastritis and restores normal gastric physiology, accelerates healing of peptic ulcer disease, and virtually eliminates recurrence of duodenal ulcer disease. The infection also plays an important role in the initiation and/or progression of gastric atrophy and intestinal metaplasia, which may eventually lead to the development of distal gastric cancer. Furthermore, almost all patients with gastric MALT lymphoma are infected with H. pylori and cure of the infection leads to histological regression of the tumor and maintains the regression in over 80% of patients during long-term follow-up. Preliminary uncontrolled data from Japan show that eradication of the infection significantly reduced metachronous intestinal-type gastric cancer following initial endoscopic resection of early gastric cancer and might also prevent the progression of gastric adenoma to gastric dysplasia or gastric cancer. Although this overwhelming evidence has demonstrated that H. pylori infection is bad for humans, some have questioned the wisdom of eradicating the infection in all those infected. Their arguments are largely based on hypothesis and circumstantial evidence: 1) Less than 20% of all H. pylori infected persons will develop significant clinical consequences in their lifetime. 2) H. pylori strains are highly diverse at a genetic level and are of different virulence. 3) The antiquity of H. pylori infection in humans and their co-evolution suggests that H. pylori may be a commensal to humans. Eradication of H. pylori may remove some beneficial bacterial strains and may provoke esophageal disease or gastric cancer at the cardia. However, careful review of the literature confirms that H. pylori infection is a serious pathogen albeit in a minority of those infected. It remains for carefully designed prospective studies, rather than hypothesis to make changes in the current consensus position. [source]

The Moral Economy of Tobacco

David Griffith
ABSTRACT Even faced with overwhelming evidence that tobacco threatens human health, along with economic developments undermining their status as independent producers, North Carolina tobacco farmers view tobacco production in ways congruent with a moral economy. A shift from independent to contract production of tobacco and the dismantling of government price supports have challenged this moral economy, converting tobacco producers into a quasi,working class dependent on tobacco companies while leading to fewer tobacco farms and an increase in the average tobacco farm's size. These changes signal a shift away from a moral economy of tobacco, although moral-economic dimensions remain. Producers today emphasize different moral dimensions of economic behavior, such as producing quality human beings, than during earlier eras, when moral-economic actors pressed for state intervention in economic crises. Moral-economic principles are not restricted to either non-Western or historical peoples but, rather, influence economic production and ideology in advanced capitalist settings today. [source]

A full-UV spectrum absorbing daily use cream protects human skin against biological changes occurring in photoaging

S. Seité
Background: There is overwhelming evidence that exposure of human skin to ultraviolet radiations (UVR) leads to the development of cutaneous photoaging and eventually to neoplasia. This study was designed to evaluate in humans the protection afforded by a daily use cream containing a photostable combination of UVB and UVA absorbers (Uvinul® N539, Parsol® 1789 and Mexoryl® SX) providing a continuous absorption through the entire UV spectrum, against damages induced by repeated daily exposure to solar simulated radiation (SSR). Methods: Buttock skin of 12 healthy volunteers was exposed 5 days per week for 6 weeks to one minimal erythema dose of solar simulated radiation per exposure. The following parameters in treated and untreated skin were evaluated: erythema, pigmentation, skin hydration, skin microtopography, histology and immunochemistry, and collagen and metalloproteinase (MMP) mRNA levels. Results: In SSR exposed unprotected skin sites, we observed melanization and changes in the skin hydration and microtopography. The epidermis revealed a significant increase in stratum corneum and stratum granulosum thickness. In the dermis, an enhanced expression of tenascin and a reduced expression of type I pro-collagen were evidenced just below the dermal epidermal junction. Although we were unable to visualize any change in elastic fibers in exposed buttock skin, a slightly increased deposition of lysozyme and alpha 1 antitrypsin on these fibers was observed using immunofluorescence techniques. Furthermore, types I and III collagen mRNA were slightly increased and a significant enhancement (up to 2.8-fold) of MMP-2 mRNA level was observed. The daily use cream was shown to prevent all these biological changes. Conclusion: Our results show in vivo that an appropriate full-UV spectrum product significantly reduces the solar-UV-induced skin damage, demonstrating the benefit of daily photoprotection. [source]

Non-linear finance,growth nexus

A threshold with instrumental variable approach
Financial development; economic growth; instrumental variable; threshold regression Abstract This paper revisits the question of whether the finance,growth nexus varies with the stages of economic development. Using a novel threshold regression with the instrumental variables approach proposed by Caner and Hansen (2004) to the dataset used in Levine et al. (2000) we detect overwhelming evidence in support of a positive linkage between financial development and economic growth, and this positive effect is larger in the low-income countries than in the high-income ones. The data also reveal that financial development tends to have stronger impacts on capital accumulation and productivity growth in the low-income countries than in the high-income ones. The findings are robust to alternative financial development measures and conditioning information sets. [source]

Carvedilol in the failing heart

William L. Lombardi M.D.
Abstract Patients with chronic heart failure due to left ventricular systolic dysfunction of ischemic or nonischemic etiology have shown improvement in morbidity and mortality with carvedilol therapy. In patients with symptomatic (New York Heart Association class II,IV) heart failure, carvedilol improves left ventricular ejection fraction and clinical status, and slows disease progression, reducing the combined risk of mortality and hospitalization. Despite the overwhelming evidence for their benefit, there continues to be a large treatment gap between those who would derive benefit and those who actually receive the drug. In this article, the pharmacology, clinical trial evidence, and the potential differences between carvedilol and other beta blockers are discussed. Carvedilol provides powerful therapy in the treatment of chronic heart failure caused by a variety of etiologies and in a wide array of clinical settings. [source]