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At least 541 records · Page 30Linked to original sources

PubMed2003

Vesicular glutamate transporters in the brain.

Glutamate is an excitatory amino acid that acts as a major neurotransmitter throughout the brain. Although its neurotransmitter action has been evidenced by the identification of various receptor subtypes at synapses, a cellular mechanism by which this amino acid accumulates in synaptic vesicles has long been in doubt until the discovery in recent years of specific vesicular transporters. Three kinds of transporter isoforms have so far been cloned and their transport properties and distribution in the brain have been studied extensively. In contrast with the apparently similar ability of all transporter isoforms to highly selectively transport glutamate and their presence in synaptic vesicles, their regional distribution of gene expression and immunoreactivity in the rodent or human brain are surprisingly different from one another. This indicates that the glutamatergic neuron system of mammalian brains is substantially comprised of at least three different neuron subpopulations, each of which uses a unique transport system for the vesicular storage of glutamate. Thus, we now have highly useful and reliable tools for a comprehensive understanding of the glutamatergic neuron system in the brain from a new viewpoint different from that of other components, such as receptors. The scope of the present review is to provide an overview of the history and present status of the study of vesicular glutamate transporters and to highlight some unresolved issues requiring clarification for the progress of future brain function research.

Amino Acid Sequence↗

PubMed2001

A concept analysis of malnutrition in the elderly.

PURPOSE: Malnutrition is a frequent and serious problem in the elderly. Today there is no doubt that malnutrition contributes significantly to morbidity and mortality in the elderly. Unfortunately, the concept of malnutrition in the elderly is poorly defined. The purpose of this paper is to clarify the meaning of malnutrition in the elderly and to develop the theoretical underpinnings, thereby facilitating communication regarding the phenomenon and enhancing research efforts. SCOPE, SOURCES USED: Critical review of literature is the approach used to systematically build and develop the theoretical propositions. Conventional search engines such as Medline, PsyINFO, and CINAHL were used. The bibliography of obtained articles was also reviewed and additional articles identified. Key wards used for searching included malnutrition, geriatric nutrition, nutritional status, nutrition assessment, elderly, ageing, and weight loss. CONCLUSIONS: The definition of malnutrition in the elderly is defined as following: faulty or inadequate nutritional status; undernourishment characterized by insufficient dietary intake, poor appetite, muscle wasting and weight loss. In the elderly, malnutrition is an ominous sign. Without intervention, it presents as a downward trajectory leading to poor health and decreased quality of life. Malnutrition in the elderly is a multidimensional concept encompassing physical and psychological elements. It is precipitated by loss, dependency, loneliness and chronic illness and potentially impacts morbidity, mortality and quality of life.

Aged↗

PubMed2002

Neonatal tetanus elimination in Mpumalanga Province, South Africa.

Neonatal tetanus (NNT) is a serious but preventable disease, and the World Health Organization (WHO) wants to eliminate NNT globally by reducing its incidence to <1 case per 1000 live births. South Africa adopted this goal in 1995, but Mpumalanga, a rural province, has consistently reported cases of NNT despite an appropriate vaccination strategy to eliminate the disease. The aim of the study was to investigate the completeness of the passive notification system and to explore reasons for ongoing NNT cases despite implementation of the provincial vaccination strategy. We reviewed all hospital admissions in the province between 1996 and 2000 meeting the case definition for NNT and interviewed mothers of the NNT cases reported in 2000. We identified 26 NNT cases, of which only 14 (54%) were reported through the routine notification system. Most cases occurred as a result of the cultural practice of applying cow dung or rat faeces to the umbilical stump in the neonatal period. Although all districts met the WHO elimination target during the review period, there is scope to prevent unnecessary NNT deaths through culturally acceptable public awareness campaigns aimed at changing harmful practices, and encouraging hygienic births and postnatal cord care.

Disease Notification↗

PubMed1995

The speed tuning of medial superior temporal (MST) cell responses to optic-flow components.

The responses of macaque medial superior temporal (MST) cells to translation and to the optic-flow components-rotation, expansion/contraction, and deformation-were examined with particular regard to the speed tuning of MST cells for optic-flow stimuli and the effect of removing speed gradients from those stimuli. The use of position invariance as an indispensable criterion for assessing the authenticity of responses to optic flow is reviewed. By extending the scope of testing to include higher speeds it is found, in contrast to in previous reports, that MST cells generally respond to optic-flow components with a speed-response profile which is tuned for a particular range of speeds. Removal of the speed gradient had little effect on this observation. These and other properties of MST cells lead to the conclusion that one of the major functions of MST is the detection and encoding of self-motion.

Animals↗

PubMed2000

Military deployment toxicology: a program manager's perspective.

The Persian Gulf War drew attention to the potential hazards of chemicals that personnel may encounter during military operations and deployments overseas. During the War, the oil well fires of Kuwait highlighted the military threat of industrial chemicals in the area of operations. Following the War, the occurrence of Gulf War Illnesses brought home concerns and suspicions regarding "low level" and "mixed" exposures to chemicals. The public's concern and attention resulted in numerous institutional responses to the real and perceived problems of health risks during military deployments. These institutional responses ranged in scope from a Presidential Review Directive to the initiative known as the Deployment Toxicology Research, Development, Testing and Evaluation (RDT&E) Program. Most institutions, however, seem to agree that additional research is needed to assess the health risks from chemical exposures during military deployments. Establishing and managing an effective RDT&E program in risk assessment for deployed forces is a challenging enterprise. The Deployment Toxicology RDT&E Program was conceived utilizing the military's acquisition framework, an effective methodology with a proven record of fielding of new technologies. Based on a series of structured meetings with military representatives that would utilize new risk assessment tools, a hierarchical set of plans was developed to identify and prioritize end products. The challenge ahead for the Deployment Toxicology RDT&E Program is to execute these plans, provide the necessary oversight, and transition the results into successful product development.

Animals↗

PubMed2005

Genome size, quantitative genetics and the genomic basis for flower size evolution in Silene latifolia.

BACKGROUND AND AIMS: The overall goal of this paper is to construct an overview of the genetic basis for flower size evolution in Silene latifolia. It aims to examine the relationship between the molecular bases for flower size and the underlying assumption of quantitative genetics theory that quantitative variation is ultimately due to the impact of a number of structural genes. SCOPE: Previous work is reviewed on the quantitative genetics and potential for response to selection on flower size, and the relationship between flower size and nuclear DNA content in S. latifolia. These earlier findings provide a framework within which to consider more recent analyses of a joint quantitative trait loci (QTL) analysis of flower size and DNA content in this species. KEY RESULTS: Flower size is a character that fits the classical quantitative genetics model of inheritance very nicely. However, an earlier finding that flower size is correlated with nuclear DNA content suggested that quantitative aspects of genome composition rather than allelic substitution at structural loci might play a major role in the evolution of flower size. The present results reported here show that QTL for flower size are correlated with QTL for DNA content, further corroborating an earlier result and providing additional support for the conclusion that localized variations in DNA content underlie evolutionary changes in flower size. CONCLUSIONS: The search image for QTL should be broadened to include overall aspects of genome regulation. As we prepare to enter the much-heralded post-genomic era, we also need to revisit our overall models of the relationship between genotype and phenotype to encompass aspects of genome structure and composition beyond structural genes.

Biological Evolution↗

PubMed2006

Conserved features of germination and polarized cell growth: a few insights from a pollen-fern spore comparison.

BACKGROUND: The germination of both pollen and fern spores results in the emergence of a cell-pollen tube from pollen, rhizoid from spore-that grows in a polar fashion, primarily at its apical end. In both of these tip-growing cells, the delivery of secretory vesicles to the growing end is guided in part by a calcium gradient, with calcium entering at the tip where it is most highly concentrated. The similarities between the two systems extend beyond tip-focused calcium gradients to encompass signalling pathways and elements including calmodulin, nitric oxide, annexins and Rop-GTPases. SCOPE AND AIMS: This review is limited to those pathways and elements that function similarly in fern and pollen systems based on currently available evidence. The aim is to illustrate the common mechanisms by which tip growth occurs, facilitate further investigations into this area, and examine the implications for the evolutionarily conserved control of tip growth. CONCLUSIONS: The interplay of calcium, nitric oxide and other effectors in both pollen and fern spores suggests certain signalling pathways became important regulators of germination and growth early in the evolution of land plants. Both large- and small-scale comparative genomic methods have shown to be promising in their ability to find new and relevant comparisons for further research. Cross-species comparisons may serve to speed up this process by highlighting both basic pathways and system-specific deviations.

Arabidopsis↗

PubMed2002

Patient demographic and socioeconomic characteristics in the SEER-Medicare database applications and limitations.

Users of the linked SEER-Medicare database commonly perform analyses that focus on the complex interactions among patient characteristics, cancer treatments, and outcomes. The authors review the source and scope of the patient-specific data elements, with a focus on three domains--demographic characteristics, socioeconomic characteristics, and survival status. They offer some concrete recommendations regarding the use of these data elements. In particular, they describe analyses that provide an estimate of the accuracy of the sex and age variables, and raise some cautionary notes about race and ethnicity variables. The authors describe the available measures of socioeconomic status, and recommend, with some caveats, the use of median income measures as a proxy for socioeconomic status. Finally, they describe the available data on date of death, and explain why confidence in these measures is justified.

Aged↗

PubMedDate not supplied

Radiograph assessment of the basal thumb joint.

Evaluation and treatment of basal thumb joint problems require a careful history, physical examination, and radiographs. The "true" AP and stress views provide useful information which supplements the standard plain radiographs. Additional maneuvers such as local injection and other imaging modalities are also sometimes employed, but their discussion is beyond the scope of this brief review.

Humans↗

PubMed2004

Recent advances in drug action and therapeutics: relevance of novel concepts in G-protein-coupled receptor and signal transduction pharmacology.

PROBLEM STATEMENT: During especially the past two decades many discoveries in biological sciences, and in particular at the molecular and genetic level, have greatly impacted on our knowledge and understanding of drug action and have helped to develop new drugs and therapeutic strategies. Furthermore, many exciting new drugs acting via novel pharmacological mechanisms are expected to be in clinical use in the not too distant future. SCOPE AND CONTENTS OF REVIEW: In this educational review, these concepts are explained and their relevance illustrated by examples of drugs used commonly in the clinical setting, with special reference to the pharmacology of G-protein-coupled receptors. The review also addresses the basic theoretical concepts of full and partial agonism, neutral antagonism, inverse agonism and protean and ligand-selective agonism, and the relevance of these concepts in current rational drug therapy. Moreover, the mechanisms whereby receptor signalling (and eventually response to drugs) is fine-tuned, such as receptor promiscuity, agonist-directed trafficking of receptor signalling, receptor trafficking, receptor 'cross-talk' and regulators of G-protein signalling (RGSs) are discussed, from theory to proposed therapeutic implications. CONCLUSIONS: It is concluded that the understanding of molecular receptor and signal transduction pharmacology enables clinicians to improve their effective implementation of current and future pharmacotherapy, ultimately enhancing the quality of life of their patients.

Cell Communication↗

PubMed2004

Long dsRNA and silent genes strike back:RNAi in mouse oocytes and early embryos.

RNA interference (RNAi) refers to the selective degradation of mRNA induced by double-stranded RNA (dsRNA), first discovered in Caenorhabditis elegans. Homology-dependent silencing phenomena related to RNAi have been observed in many species from all eukaryotic kingdoms. RNAi and related mechanisms share several conserved components. The hallmark of these phenomena is the presence of short dsRNA molecules (21-25 bp long), termed short interfering RNA (siRNA), which are generated from dsRNA by the activity of Dicer, a specific type III RNAse. These molecules serve as a template for the recognition and cleavage of the cognate mRNA. As it is beyond the scope of a single review to cover all aspects of RNAi, this review will focus on certain steps of the pathway relevant to mammals and on the use of long dsRNA to specifically silence genes in mammalian cells permissive to this technique, such as oocytes and early embryos.

Animals↗

PubMed2005

Diabetes and cardiovascular risk markers.

BACKGROUND: People with type 2 diabetes generally carry an array of risk factors for cardiovascular disease (CVD), including hyperglycaemia, dyslipidaemia, alterations in inflammatory mediators and coagulation/thrombolytic parameters, as well as other 'non-traditional' risk factors, many of which may be closely associated with insulin resistance. Consequently, rates of CVD mortality and morbidity are particularly high in this population. Targeting hyperglycaemia alone does not reduce the excess risk in diabetes, highlighting the need for aggressive treatment of other risk factors. SCOPE: This is a review of cardiovascular risk markers in diabetes, based on MEDLINE and EMBASE literature searches (1994-2004). FINDINGS: Although, the current use of statin therapy is effective at reducing low-density lipoprotein (LDL)-cholesterol, residual risk remains from other independent lipid and non-lipid factors. The peroxisome proliferator-activated receptor-gamma(PPARgamma) appears to be intimately involved in regulating risk markers at multiple levels. Ligands that activate PPARgamma, which include the thiazolidinedione (TZD) insulin-sensitizing agents used to manage type 2 diabetes, display a number of potential anti-atherogenic properties, including effects on high-density lipoprotein (HDL) cholesterol and triglycerides, as well as other beneficial non-lipid effects, such as regulating levels of mediators involved in inflammation and endothelial dysfunction. Data from several sources suggest that simple strategies combining TZDs and statins could have complementary effects on CVD risk factors profiles in diabetes, alongside the ability to control glycaemia. CONCLUSION: It is hoped that studies currently underway will provide insights into the value of such treatment approaches in terms of reducing the excess CVD risk, morbidity and mortality associated with type 2 diabetes.

Biomarkers↗

PubMed2006

Clinical implications for vascular endothelial growth factor in the lung: friend or foe?

Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis which has multiple effects in lung development and physiology. VEGF is expressed in several parts of the lung and the pleura while it has been shown that changes in its expression play a significant role in the pathophysiology of some of the most common respiratory disorders, such as acute lung injury, asthma, chronic obstructive pulmonary disease, obstructive sleep apnea, idiopathic pulmonary fibrosis, pulmonary hypertension, pleural disease, and lung cancer. However, the exact role of VEGF in the lung is not clear yet, as there is contradictory evidence that suggests either a protective or a harmful role. VEGF seems to interfere in a different manner, depending on its amount, the location, and the underlying pathologic process in lung tissue. The lack of VEGF in some disease entities may provide implications for its substitution, whereas its overexpression in other lung disorders has led to interventions for the attenuation of its action. Many efforts have been made in order to regulate the expression of VEGF and anti-VEGF antibodies are already in use for the management of lung cancer. Further research is still needed for the complete understanding of the exact role of VEGF in health and disease, in order to take advantage of its benefits and avoid its adverse effects. The scope of the present review is to summarize from a clinical point of view the changes in VEGF expression in several disorders of the respiratory system and focus on its diagnostic and therapeutic implications.

Angiogenesis Inhibitors↗

PubMed2003

Gene profiling for defining targets for new therapeutics in autoimmune diseases.

The identification of novel targets for improved diagnosis and pharmaceutical intervention is of critical importance for better treatment of autoimmune diseases in the future. The possibility to measure levels of gene expression for tens of thousands of genes simultaneously and in a quantitative fashion will greatly enhance our knowledge of genes and pathways involved in disease pathogenesis. Initial studies have focused on the gene expression profiling of homogeneous cell populations. Genomic-scale gene expression profiling has also more recently been applied to tissue samples from patients with immunopathologies. The scope of the present review is to discuss recent progress in this field with respect to the identification of novel target molecules.

Animals↗

PubMed1995

[Uses of hydroxamic acids and of N-alkoxyimidoyl halides in organic synthesis].

Although N-hydroxyamides (1) have been known for over a century, the chemistry of 1 is still relatively unexplored. The scope of the present review is a survey of the recent advances of the chemistry of 1 and its derivatives, particularly of new chemical reactions having synthetic utility in organic synthesis developed mainly in our laboratory. The review is divided into two sections. The first section described great utility of divalent positively-charged nitrogen species generated from 1 in synthesis. Electrophilic intramolecular cyclization with an acylnitrenium ion generated from an N-methoxy- or an N-allyloxy-N-chloroamide with anhydrous zinc acetate in nitromethane gave an N-methoxy- or an N-allyloxy nitrogen heterocyclic compound, deprotection of which led to formation of the corresponding N-hydroxy compound. Treatment of an N-hydroxy- or an N-methoxy-N-arylamide and the corresponding lactam with various reagents results in removal of the hydroxy or methoxy function and introduction of nucleophiles at the ortho or para position of the aromatic ring. These methodologies were successfully applied by us for the synthesis of the alkaloid, eupolauramine and for new oxindoles related to the alkaloid, gelsemine, by others. The second section described great utility of N-alkoxyimidoyl halides (2) synthesized from 1. Compounds 2 were readily transformed to other functions such as aldehydes, cyanides, and oximes. This methodology was successfully applied to the synthesis of omega-N-hydroxy-alpha-amino acids in optically pure form which were the key intermediates for the synthesis of hydroxamate-containing siderophores.

Hydroxamic Acids↗

PubMed2003

Low-shrink monomers for dental restorations.

The main disadvantages of resin-based composites (RBCs) for use in load-bearing posterior restorations include the polymerization shrinkage following curing and inadequate wear resistance in service. These properties are largely influenced by the monomer system and research is currently being undertaken to decrease polymerization shrinkage and improve resin wear characteristics in an attempt to increase RBC restoration longevity. The scope of the current review will identify the development of resin-based restoratives, indicating the reported advantages and disadvantages of resin types routinely used in dental practice today and review the most recent advancements in resin technology.

Composite Resins↗

PubMed2005

Investigational anti-inflammatory agents for the treatment of ischaemic brain injury.

Stroke is the third leading cause of death and the leading cause of disability in Western countries. To date, only approximately 2% of stroke patients are eligible for thrombolysis treatment with recombinant tissue plasminogen activator. The very limited options available for stroke treatment and recent disappointing clinical trials in stroke call for novel therapeutic approaches. Inflammation represents one of the key pathophysiological mechanisms for the progression of ischaemic stroke. Recent advances in preclinical models of stroke using investigational small molecular antagonists, neutralising antibodies/proteins or genetically altered gene functions against various inflammatory mediators suggest a great therapeutic potential of anti-inflammation for ischaemic stroke. The scope of the present review is to update the evidence for a role of inflammatory pathways in stroke and to summarise the investigational drugs currently available both in preclinical and clinical development for potential treatment of ischaemic stroke.

ADAM Proteins↗

PubMed1997

Cell and molecular biology for neurosurgeons (or everything you wanted to know about molecular biology but were afraid to download).

We are fortunate to be physicians at a time when the molecular pathogenesis of disease is being unraveled. Beginning with the discovery of the structure of DNA to the Human Genome Project, molecular biology over the past 45 years has revolutionized medicine. Neurosurgery has a strong scientific tradition, but to remain active participants in this new era of medicine, we must understand the science of pathology at the molecular level, applying our unique perspective to its advancement. We will review most of the current techniques used today by cell and molecular biologists. Interwoven with these descriptions will be a brief discussion of pertinent molecular and cell biology concepts, a full review being beyond the scope of this article.

Journal Article↗