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At least 433 records · Page 24Linked to original sources
PubMed2004

The role of oxygen in neonatal resuscitation.

New knowledge has accumulated in recent years making it prudent to ask questions regarding current oxygenation policies and guidelines. Because new-born resuscitation affects so many individuals, and because resuscitation procedures may have dramatic consequences on infant and child health, intensified discussion and research in this field are not only necessary but are a requirement. In particular, there is a lack of data on infants born before term. It is difficult to give absolute recommendations on which oxygen concentration should be applied for newborn resuscitation; however, it seems that ambient air is safe. It is easy to handle, is always at hand, and is inexpensive. Conversely, regarding 100% O2, I believe we have sufficient data to conclude that this should not be given routinely at birth to depressed infants; however, whether it is beneficial or harmful to start out resuscitation with 30%, 40%, or 60% O2 is not known. No data exist to answer this question. A call for more research in this area is timely. The effect of pure oxygen on cell growth and cell death, gene activation, and possibly DNA damage should be carefully investigated. Even before such data are collected, it is known that pure oxygen at birth triggers long-term and poorly understood effects. Oxygen obviously is more toxic than previously thought, and oxygen given to small infants has a 50-year history of uncertain benefits. Table 1 summarizes the pros and cons of using 21%versus 100% 02 for newborn resuscitation. Brain circulation as assessed by microspheres is restored as quickly with 21% O2 as it is with 100% O2; however, microcirculation is somewhat slower. Metabolism, pulmonary flow, and myocardial performance are normalized just as quickly by 21% and 100% O2. Brain injury as assessed by glycerol augmentation, matrix injury, and neonatal mortality is less in infants given 21% versus 100% O2.

Air↗
PubMedDate not supplied

Dorsal and ventral streams: a framework for understanding aspects of the functional anatomy of language.

Despite intensive work on language-brain relations, and a fairly impressive accumulation of knowledge over the last several decades, there has been little progress in developing large-scale models of the functional anatomy of language that integrate neuropsychological, neuroimaging, and psycholinguistic data. Drawing on relatively recent developments in the cortical organization of vision, and on data from a variety of sources, we propose a new framework for understanding aspects of the functional anatomy of language which moves towards remedying this situation. The framework posits that early cortical stages of speech perception involve auditory fields in the superior temporal gyrus bilaterally (although asymmetrically). This cortical processing system then diverges into two broad processing streams, a ventral stream, which is involved in mapping sound onto meaning, and a dorsal stream, which is involved in mapping sound onto articulatory-based representations. The ventral stream projects ventro-laterally toward inferior posterior temporal cortex (posterior middle temporal gyrus) which serves as an interface between sound-based representations of speech in the superior temporal gyrus (again bilaterally) and widely distributed conceptual representations. The dorsal stream projects dorso-posteriorly involving a region in the posterior Sylvian fissure at the parietal-temporal boundary (area Spt), and ultimately projecting to frontal regions. This network provides a mechanism for the development and maintenance of "parity" between auditory and motor representations of speech. Although the proposed dorsal stream represents a very tight connection between processes involved in speech perception and speech production, it does not appear to be a critical component of the speech perception process under normal (ecologically natural) listening conditions, that is, when speech input is mapped onto a conceptual representation. We also propose some degree of bi-directionality in both the dorsal and ventral pathways. We discuss some recent empirical tests of this framework that utilize a range of methods. We also show how damage to different components of this framework can account for the major symptom clusters of the fluent aphasias, and discuss some recent evidence concerning how sentence-level processing might be integrated into the framework.

Aphasia↗
PubMed2005

Homing to suppress: address codes for Treg migration.

Compelling evidence suggests that diverse types of immune reactions can be suppressed by CD25+ CD4+ regulatory T cells (Tregs). Although increasing knowledge has accumulated concerning the generation and functional properties of Tregs, relatively little attention has been paid to another key question: where does immune regulation by Tregs take place in vivo? Tregs can inhibit both the priming and the effector phase of an immune response, so suppression might occur both within lymphoid tissues and at peripheral sites during immune reactions. This leads to the hypothesis that appropriate localization is indispensable for in vivo Treg function and that the migratory behavior of Treg subsets influences their in vivo suppressive capacity. Current data suggest a division of labor between subpopulations of Tregs, which is mainly based on specialized homing patterns.

Animals↗
PubMed2005

Signalling and gene regulation in response to ultraviolet light.

In contrast to phytochrome-, cryptochrome- and phototropin-sensing systems, about which considerable knowledge has accumulated, the ultraviolet-B (UVB) photoreceptor is not yet known at the molecular level. Information about the downstream signalling events that underlie UVB-provoked physiological responses is limited. Recent whole-genome transcript profiling, isolation of mutants that are impaired in specific UVB-induced responses and detailed photobiological studies suggest that responses that are triggered by shorter wavelength UVB and longer wavelength UVB are mediated by two different sensory systems. The bZIP transcription factor HY5 was recently identified as an important player in the long-wavelength UVB-induced signal transduction cascade. Advances in the development of luciferase-reporter lines will make it feasible to perform high-throughput genetic screens to isolate novel mutants that are impaired in sensing or transducing signals downstream of the putative UVB photoreceptor(s).

Gene Expression Regulation, Plant↗
PubMed2004

The harm done by tests of significance.

Three historical episodes in which the application of null hypothesis significance testing (NHST) led to the mis-interpretation of data are described. It is argued that the pervasive use of this statistical ritual impedes the accumulation of knowledge and is unfit for use.

Accidents, Traffic↗
PubMed2003

Hereditary kidney cancer.

Significant advances have been made in the understanding of the genetic basis of familial renal neoplasia. Identification of key genes in the pathogenesis of various hereditary renal cancer syndromes has provided opportunities to screen family members at risk and to explore the significance of these genetic abnormalities in the development and genesis of much more common sporadic counterparts. As researchers continue to delineate critical carcinogenic pathways and accumulate expansive knowledge on oncogenic mechanisms driving cancer initiation and progression at the cellular and molecular levels, this information will be integrated and translated into effective diagnostic and therapeutic strategies that will dictate clinical management of all renal cancers.

Humans↗
PubMed2003

Oligodendroglia in developmental neurotoxicity.

The developing nervous system has been long recognized as a primary target for a variety of toxicants. To date, most efforts to understand the impact of neurotoxic agents on the brain have focused primarily on neurons and to a lesser degree astroglia as cellular targets. The role of oligodendroglia, the myelin-forming cells in the central nervous system (CNS), in developmental neurotoxicity has been emphasized only in recent years. Oligodendrocytes originate from migratory, mitotic progenitors that mature progressively into postmitotic myelinating cells. During differentiation, oligodendroglial lineage cells pass through a series of distinct phenotypic stages that are characterized by different proliferative capacities and migratory abilities, as well as dramatic changes in morphology with sequential expression of unique developmental markers. In recent years, it has become appreciated that oligodendrocyte lineage cells have important functions other than those related to myelin formation and maintenance, including participation in neuronal survival and development, as well as neurotransmission and synaptic function. Substantial knowledge has accumulated on the control of oligodendroglial survival, migration, proliferation, and differentiation, as well as the cellular and molecular events involved in oligodendroglial development and myelin formation. Recently, studies have been initiated to address the role of oligodendrocyte lineage cells in neurotoxic processes. This article examines recent progress in oligodendroglial biology, focuses attention on the characteristic features of the oligodendrocyte developmental lineage as a model system for neurotoxicological studies, and explores the role of oligodendrocyte lineage cells in developmental neurotoxicity. The potential role of oligodendroglia in environmental lead neurotoxicity is presented to exemplify this thesis.

Cell Differentiation↗
PubMed1996

Molecular biology of autoantigens in rheumatic diseases.

The advent of molecular biologic techniques has provided new approaches that are of great utility to the study of autoimmune-mediated responses. In the past few years, there has been a remarkable accumulation of knowledge concerning the molecular identity and function of autoantigens, and further consolidation for the use of autoantibodies as diagnostic markers in clinical rheumatology. The understanding of basis methodologies in molecular biology applied to the study of autoantigens, in particular, techniques for cloning and analyzing genes that are important in rheumatic diseases, is valuable for both basic scientists and clinicians interested in diagnostic and prognostic markers of various connective tissue diseases.

Autoantigens↗
PubMed2001

Identification of the protein product of the Coch gene (hereditary deafness gene) as the major component of bovine inner ear protein.

In order to better understand the cause of hereditary hearing impairment, we have performed a proteomic analysis of the inner ear proteins using two-dimensional gel electrophoresis. In the process of analysis, we have found very unique properties of the bovine homologue of the human COCH gene product. The COCH gene is responsible for one of the hereditary hearing impairments, DFNA9, and was recently suggested to be a possible genetic factor contributing to Ménière's disease. The Coch protein constitutes 70% of bovine inner ear proteins and is composed of 16 different protein spots, with charge and size heterogeneity. Heterogeneity of this protein suggests that the Coch gene is processed in several ways, at the transcriptional and/or posttranslational level. Much knowledge has accumulated about the hereditary hearing impairment genes; however, little research has been done regarding the protein products of those genes. This is the first report to characterize the Coch protein. Study of the Coch protein might provide more information on the mechanism of hearing and vestibular disorders.

Amino Acid Sequence↗
PubMed1999

Negative regulation of cytokine signaling: STAT-induced STAT inhibitor.

The growth and differentiation of cells that make up multicellular entities such as the blood and immune systems are under the control of glycoprotein mediators known as cytokines. These cytokines bind to membrane receptors on the cell surface and initiate a signaling cascade that ends with the transcription of specific sets of genes within the cell nucleus. Although knowledge is accumulating concerning the intracellular signal pathways that are activated by cytokines, little is known about inhibition of cytokine signals. This review will focus on the negative regulation of the Janus tyrosine kinase (JAK)/signal transducers and activators of transcription (STAT) signaling pathway by proteins related to STAT-induced STAT inhibitor-1 (SSI-1).

Animals↗
PubMed2003

Single-unit recording in the lateral geniculate nucleus of the awake behaving monkey.

In recent years, recording neuronal activity in the awake, behaving primate brain has become established as one of the major tools available to study the neuronal specificity of the initiation and control of various behaviors. Primates have traditionally been used in these studies because of their ability to perform more complex behaviors closely akin to those of humans, a desirable prerequisite since our ultimate aim is to elucidate the neuronal correlates of human behaviors. A wealth of knowledge has accumulated on the sensory and motor systems such as vision, audition, and eye movements. For more demanding behaviors where the main focus has been on attention, recordings in awake primates have begun to yield valuable data on the centers of the brain that are reactive to different attributes of this behavior. As a result, various hypotheses of the origin and distribution of attentional effects have evolved. For instance, visual attentional effects have been described not only in the higher cortical area (V4) but also in areas earlier in the visual pathway which presumably involve a feedback mechanism in the latter region. Here we outline the ways in which we have successfully used these methods to make single-cell recordings in awake macaques to show how certain behavioral paradigms affect neurons of the thalamus (with emphasis on the lateral geniculate nucleus). As we have done with established techniques these methods can be readily adapted to incorporate most behaviors needed to be tested and allow recordings to be made in virtually any part of the brain.

Action Potentials↗
PubMed1999

Stents for atherosclerotic renovascular disease.

There is extensive documentation of excellent clinical results with renal stents in patients who have technically failed angioplasty and who would have been expected to otherwise have a high incidence of clinical failure. In addition, the technical success of renal stents is vastly superior to that of conventional angioplasty in atherosclerotic renovascular disease, and stents have been a major factor in making the endovascular treatment of ASRVD both practical and reliable in experienced hands. Restenosis rates appear roughly equivalent or lower for stents versus PTA as far as can be determined without good comparative studies. Restenosis appears to be decreasing to 15%-20% in more recent series, perhaps because of the accumulation of knowledge regarding patient selection and techniques. It is, therefore, clear that the use of stents to treat technical failures of angioplasty will result in overall improved patency in the treated population; however, it remains to be determined whether stents should be routinely placed with the intention of inhibiting restenosis, in the presence of technically successful angioplasty with minimal residual stenosis or pressure gradient. Such a determination may require comparative study that is more complicated than a simple randomized comparison of angioplasty versus stents.

Algorithms↗
PubMed1995

The outcomes of ESRD and its treatment.

In recent years, the notion that studying outcomes is a distinct form of clinical research has gained currency. This article offers a conceptual framework for thinking about outcomes research in end-stage renal disease and examines one issue in detail. Although the meaning of the term "outcome" is often assumed, it is currently used in two ways. In the broader sense, outcomes are the results of health care. These may include survival and the presence or absence of symptoms and clinical signs of disease. As it has recently been used in the medical literature, however, the term outcomes frequently connotes outcomes with respect to patient function and experience. Patient experience comprises functional status, general well-being, and satisfaction with care. The principle that the outcomes of end-stage renal disease should be studied has been established. A substantial body of knowledge has accumulated regarding characteristics of the patient population, of the treatments administered, and of the consequences with respect to survival. Whether the investigation and practice of renal replacement therapy should encompass the measurement of patient experience has been a subject of controversy. Reasons to perform such measurements are enumerated, and countervailing arguments are examined critically. The technological prerequisites for success in the widespread measurement of patient experience are set forth.

Humans↗
PubMed2006

Computational biology in the study of cardiac ion channels and cell electrophysiology.

The cardiac cell is a complex biological system where various processes interact to generate electrical excitation (the action potential, AP) and contraction. During AP generation, membrane ion channels interact nonlinearly with dynamically changing ionic concentrations and varying transmembrane voltage, and are subject to regulatory processes. In recent years, a large body of knowledge has accumulated on the molecular structure of cardiac ion channels, their function, and their modification by genetic mutations that are associated with cardiac arrhythmias and sudden death. However, ion channels are typically studied in isolation (in expression systems or isolated membrane patches), away from the physiological environment of the cell where they interact to generate the AP. A major challenge remains the integration of ion-channel properties into the functioning, complex and highly interactive cell system, with the objective to relate molecular-level processes and their modification by disease to whole-cell function and clinical phenotype. In this article we describe how computational biology can be used to achieve such integration. We explain how mathematical (Markov) models of ion-channel kinetics are incorporated into integrated models of cardiac cells to compute the AP. We provide examples of mathematical (computer) simulations of physiological and pathological phenomena, including AP adaptation to changes in heart rate, genetic mutations in SCN5A and HERG genes that are associated with fatal cardiac arrhythmias, and effects of the CaMKII regulatory pathway and beta-adrenergic cascade on the cell electrophysiological function.

Action Potentials↗
PubMed1996

The influence of the work environment on cardiovascular health: a historical, conceptual, and methodological perspective.

The framework of psychosocial epidemiology is used to examine research developments that characterize the accumulation of knowledge regarding the role of the work environment in cardiovascular health and disease. The discussion of current programs of research focuses on the work of T. Theorell and R. Karasek (1996) and J. Siegrist (1996) as exemplars of European and American studies that have contributed the most to the understanding of occupational cardiovascular health. It is argued that researchers need to maintain and nurture relatively broad conceptual models of etiology because cardiovascular disease involves multiple biomedical risk factors and because specific aspects of the work environment are embedded in a large, complex matrix of other psychosocial influences. At the same time, investigators need to push ahead with focused research strategies to clarify the precise nature of the work environmental risk factors that emerge in the broad, somewhat imprecise epidemiologic study designs.

Cardiovascular Diseases↗
PubMed2003

Heat loss, sleepiness, and impaired performance after diazepam administration in humans.

In spite of the accumulation of knowledge regarding the neuropharmacological action of benzodiazepines (Bz), the physiological process by which their sedative/hypnotic effects are induced remains poorly understood. We conducted a single-blind, crossover trial to evaluate the role of the thermoregulatory process in sleepiness and impaired psychomotor performance induced by a standard Bz, diazepam (DZP). Each of the eight healthy young male volunteers (mean age, 19.75 years; range, 18-23 years) was given a single oral dose of either 5 or 10 mg of DZP or placebo 12 h after his average sleep onset time. Changes in plasma DZP concentration, proximal body temperature (p-BT), distal body temperature (d-BT), subjective sleepiness measured by the Visual Analog Scale and Stanford Sleepiness Scale, and psychomotor performance measured by Choice Reaction Time were monitored under a modified constant routine condition in which various factors affecting thermoregulation, alertness, and psychomotor performances were strictly controlled. Orally administered DZP induced a significant transient decrease in p-BT and psychomotor performance as well as an increase in d-BT and subjective sleepiness. Distal-p-BT gradient (DPG; difference between d-BT and p-BT), which is an indicator of blood flow in distal skin regions, showed a strong positive correlation with the plasma DZP concentration, indicating that DZP in clinical doses promotes heat loss in a dose-dependent manner. The DPG also correlated positively with the magnitude of subjective sleepiness and impaired psychomotor performance. These findings indicate that the sedative/hypnotic effects of Bz could be due, at least in part, to changes in thermoregulation, especially in the process of heat loss, in humans.

Administration, Oral↗
PubMed1983

Pattern recognition in kittens: performance on Lie patterns.

Despite a vast accumulation of knowledge about the anatomy and physiology of the cat's visual system in recent years, and about its early development, there has been very little experimental study of the development of visual behaviour in this species. This is especially true of the kitten's ability to recognize patterns. Two experiments are reported that aim to remedy some part of this deficiency, and that also serves to examine a particular hypothesis about the basis of pattern analysis in the young organism. This is Hoffman's hypothesis that the orbits of elementary Lie transformation groups (a species of continuous transformation group) represent the basis for coding pattern information.

Age Factors↗
PubMed1996

Anchored narratives: the story and findings of half a century of research into the determinants of fertility.

This paper reviews half a century of research into the determinants of fertility. It is argued that the quest for the determinants of fertility behaviour and change during that period can best be interpreted as the development of a series of sub-narratives from different disciplinary perspectives and orientations. These are normally based upon the initial narrative of the demographic transition and usually take the form of a verbal theory illustrated by a 'box and arrow' diagram. On occasions formalization has been attempted. Different parts of the initial narrative have been highlighted at different times depending on policy interest, improvements in technical skills, availability of data, changes in social setting, and the degree of satisfaction with the dominant sub-narrative of the day. There is every reason to believe that the research process identified will continue and will lead to a further accumulation of knowledge. In fact, all important variables have probably already been identified. That it will, ultimately, lead to a single, consolidated narrative fully satisfactory for all settings and for all time is, however, highly unlikely.

Fertility↗