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At least 991 records · Page 55Linked to original sources
PubMed1985

Spinal cord substance P mediates bicuculline-induced activation of cardiovascular responses from the ventral medulla.

Substance P (SP) and serotonin are contained in ventral medullary projections to the intermediolateral cell column (IML) of the spinal cord, and both neurotransmitters excite sympathetic preganglionic neurons upon injection into the IML. Since gamma-aminobutyric acid (GABA) in the ventral medulla inhibits, and GABA-receptor antagonists excite sympathetic outflow to the cardiovascular system, experiments were done to determine if SP and serotonin in the spinal cord were responsible for mediating these GABAergic effects. Anesthetized rats were either given intrathecal injections of SP antagonists acutely, or pretreated with intrathecal injections of the serotonin neurotoxin, 5,7-dihydroxytryptamine. The effects of these drugs on mean arterial pressure (MAP) and heart rate (HR), as well as their ability to block the responses to topical application of GABA or the GABA antagonist, bicuculline, at the ventral medulla were assessed. Three SP antagonists (50 micrograms) decreased MAP to 2/3 baseline values, but did not change HR. They also blocked the characteristic increases in MAP and HR elicited by application of bicuculline to the ventral medulla. A lower dose (5 micrograms) of a SP antagonist also decreased MAP and blocked the bicuculline-induced increases in MAP and HR, an effect which was reversed in 1-2 h. Neonatal capsaicin treatment reduced the SP content in the dorsal horns of the thoracic spinal cord, but did not affect the cardiovascular responses to intrathecal injection of SP antagonist nor the blockade of bicuculline-induced responses. Intrathecal injection of 5,7-dihydroxytryptamine two weeks prior to the experiments resulted in 56% depletion of serotonin in the thoracic spinal cord, but did not change either basal MAP and HR, nor the responses to bicuculline and GABA applied to the ventral surface of the medulla. These data provide evidence for a role of spinal cord SP in cardiovascular regulation.

5,7-Dihydroxytryptamine↗
PubMed1994

Biomedical applications of capillary electrophoresis.

After having grown through the stages of technique development and instrumentation availability, capillary electrophoresis has reached the stage of applications. This review attempts to show the potential of this technique for biomedical analysis. Rather than going into a detailed description of the technical details of the separation conditions suitable for the separation of a particular category of compounds, the focus is on the general principles and areas in which this technique can be applied and the prospects for the future. Particular emphasis is placed on the separation of complex matrices and their simplification, a daily task in biomedical laboratories. In addition, methods for the optimization of separation conditions are considered. Considerable prospects for capillary electrophoresis lie in profiling. The applicability of the technique in peptide and protein mapping is discussed in some detail. Finally, three other topics are dealt with, namely enzymic activity microassays, drug-protein binding assays and monitoring of drugs in body fluids.

Animals↗
PubMed2000

Interpretation of chemical shifts and coupling constants in macromolecules.

Recent developments in NMR spectroscopy, along with advances in computational techniques, have produced new approaches to the interpretation of chemical shifts and spin-spin coupling constants in biomolecules. Quantum chemical studies of useful accuracy are now becoming more routine and are increasingly being used in conjunction with experimental studies to map out expected structural patterns for peptides and oligonucleotides. Topics of recent special interest include spin couplings across hydrogen bonds and patterns of chemical shift anisotropies, in both diamagnetic and paramagnetic proteins.

Anisotropy↗
PubMedDate not supplied

Recent research in organization and expression of immunoglobulin V region genes.

The first Jacques Monod Conference was held in Roscoff, Brittany on 1-5 June 1987 and dealt with the topic of 'Selection of Lymphocyte Repertoires' (organizers F. W. Alt, Columbia University, New York. P.-A. Cazenave, Institut Pasteur, Paris and A. Coutinho, Institut Pasteur, Paris). Much of the meeting was concerned with the recent developments in immunoglobulin and T-cell receptor V region organization and expression. This review is based on the contributions and discussions on Ig V genes, in particular their organization, rearrangements, allelic exclusion and somatic mutation. (Names without references indicate the conference speaker on that topic.)

Animals↗
PubMed2000

Human UDP-glucuronosyltransferases: metabolism, expression, and disease.

In vertebrates, the glucuronidation of small lipophilic agents is catalyzed by the endoplasmic reticulum UDP-glucuronosyltransferases (UGTs). This metabolic pathway leads to the formation of water-soluble metabolites originating from normal dietary processes, cellular catabolism, or exposure to drugs and xenobiotics. This classic detoxification process, which led to the discovery nearly 50 years ago of the cosubstrate UDP-glucuronic acid (19), is now known to be carried out by 15 human UGTs. Characterization of the individual gene products using cDNA expression experiments has led to the identification of over 350 individual compounds that serve as substrates for this superfamily of proteins. This data, coupled with the introduction of sophisticated RNA detection techniques designed to elucidate patterns of gene expression of the UGT superfamily in human liver and extrahepatic tissues of the gastrointestinal tract, has aided in understanding the contribution of glucuronidation toward epithelial first-pass metabolism. In addition, characterization of the UGT1A locus and genetic studies directed at understanding the role of bilirubin glucuronidation and the biochemical basis of the clinical symptoms found in unconjugated hyperbilirubinemia have uncovered the structural gene polymorphisms associated with Crigler-Najjar's and Gilbert's syndrome. The role of the UGTs in metabolism and different disease states in humans is the topic of this review.

Autoimmunity↗
PubMed2005

What is eHealth (4): a scoping exercise to map the field.

BACKGROUND: Lack of consensus on the meaning of eHealth has led to uncertainty among academics, policymakers, providers and consumers. This project was commissioned in light of the rising profile of eHealth on the international policy agenda and the emerging UK National Programme for Information Technology (now called Connecting for Health) and related developments in the UK National Health Service. OBJECTIVES: To map the emergence and scope of eHealth as a topic and to identify its place within the wider health informatics field, as part of a larger review of research and expert analysis pertaining to current evidence, best practice and future trends. METHODS: Multiple databases of scientific abstracts were explored in a nonsystematic fashion to assess the presence of eHealth or conceptually related terms within their taxonomies, to identify journals in which articles explicitly referring to eHealth are contained and the topics covered, and to identify published definitions of the concept. The databases were Medline (PubMed), the Cumulative Index of Nursing and Allied Health Literature (CINAHL), the Science Citation Index (SCI), the Social Science Citation Index (SSCI), the Cochrane Database (including Dare, Central, NHS Economic Evaluation Database [NHS EED], Health Technology Assessment [HTA] database, NHS EED bibliographic) and ISTP (now known as ISI proceedings). We used the search query, "Ehealth OR e-health OR e*health". The timeframe searched was 1997-2003, although some analyses contain data emerging subsequent to this period. This was supplemented by iterative searches of Web-based sources, such as commercial and policy reports, research commissioning programmes and electronic news pages. Definitions extracted from both searches were thematically analyzed and compared in order to assess conceptual heterogeneity. RESULTS: The term eHealth only came into use in the year 2000, but has since become widely prevalent. The scope of the topic was not immediately discernable from that of the wider health informatics field, for which over 320000 publications are listed in Medline alone, and it is not explicitly represented within the existing Medical Subject Headings (MeSH) taxonomy. Applying eHealth as narrative search term to multiple databases yielded 387 relevant articles, distributed across 154 different journals, most commonly related to information technology and telemedicine, but extending to such areas as law. Most eHealth articles are represented on Medline. Definitions of eHealth vary with respect to the functions, stakeholders, contexts and theoretical issues targeted. Most encompass a broad range of medical informatics applications either specified (eg, decision support, consumer health information) or presented in more general terms (eg, to manage, arrange or deliver health care). However the majority emphasize the communicative functions of eHealth and specify the use of networked digital technologies, primarily the Internet, thus differentiating eHealth from the field of medical informatics. While some definitions explicitly target health professionals or patients, most encompass applications for all stakeholder groups. The nature of the scientific and broader literature pertaining to eHealth closely reflects these conceptualizations. CONCLUSIONS: We surmise that the field -- as it stands today -- may be characterized by the global definitions suggested by Eysenbach and Eng.

Delivery of Health Care↗
PubMedDate not supplied

Methodological issues in the development of the Canadian Cancer Incidence Atlas.

The Canadian Cancer Incidence Atlas is among recent national atlases using incidence rather than mortality data. Methods used to assess the significance and spatial correlation of the age-standardized rates (ASIRs) for the 290 census divisions are described. The expected number of cases by area was used to determine cancer sites with sufficient cases to be mapped. ASIR significance was assessed using a simulation based on a Poisson distribution. The consistency of the observed case distributions with the Poisson distribution was examined. The bootstrap confidence interval (CI) for the ASIR developed by Swift was used in the atlas. Spatial correlation was assessed with Moran's I/I(max) and the significance determined by a simulation in order to allow for area population variation. Data quality indicators typically used for cancer registries were presented, supplemented by a registry questionnaire.

Atlases as Topic↗
PubMed2004

Mapping disease-susceptibility genes in admixed populations using interval principal component tests.

Family-based association approach for mapping disease-susceptibility genes of complex human diseases is a topical issue in genetic epidemiology. It is well known that admixture between genetically differentiated populations can result in high levels of linkage disequilibrium at loci separated far apart. This property has been capitalized upon to reduce the burden of genotyping in a genomewide association scan. The authors describe a new approach for admixture mapping--the "interval principal component test" (IPCT). The genome is divided into a multitude of non-overlapping "intervals" (with interval length of 10-20 cM) and the information of the markers in the same interval is integrated using the principal component analysis. Monte-Carlo simulation shows that an interval-by-interval scan using IPCT has much better performances than a conventional marker-by-marker scan using the transmission/disequilibrium test (TDT).

Computer Simulation↗
PubMed1993

Neuroregulation of a chemosensitive afferent system in the canine distal esophagus.

Systemic and local responses mediated by chemonociceptive receptors located in the mucosa of the canine distal esophagus were examined following stimulation with capsaicin (8-methyl-N-vanillyl-6-nonenamide). The neural pathways and neurotransmitters mediating these sensory responses were also investigated. Topical application of capsaicin solution to the distal esophageal mucosa produced significant increases in lower esophageal sphincter pressure (LESP), mean arterial pressure (MAP), pulse rate (PR), and respiratory rate (RR) (P < 0.01). Pretreatment with tetrodotoxin completely abolished this reflex activity. Following truncal vagotomy and pyloroplasty, topical capsaicin application produced an increase in LESP, but the increases in MAP, PR, and RR were blocked. The initial increase in LESP was blocked by hexamethonium, atropine, and 4-diphenylacetoxy-N-methylpiperidine, but was not inhibited by phentolamine. Excitatory cardiovascular responses were inhibited by hexamethonium. Administration of a Substance P antagonist attenuated both local and systemic responses. These studies suggest that the vagus nerves serve as the primary afferent pathways through which chemonociceptive esophageal stimuli can induce cardiovascular and respiratory reflex excitation. The increase in lower esophageal sphincter pressure in response to mucosal capsaicin stimulation is mediated via an intrinsic neural pathway that functions independently of vagal innervation, but is dependent on both cholinergic ganglionic neurotransmission and muscarinic type 2 smooth muscle receptor excitation. Substance P appears to play a role in primary sensory afferents as a chemonociceptive neurotransmitter in the canine distal esophagus.

Afferent Pathways↗
PubMed1994

On the limitations of automated restriction mapping.

Eight important restriction mapping programs, developed between 1978 and 1993, are analyzed and their performance evaluated. The analyses concentrate on the practical value of the programs to molecular biologists who do restriction mapping on a daily basis, rather than on theoretical efficiency. Although all of the programs could find maps consistent with the data, none were able to discriminate reliably the true map from the other consistent maps, given realistic levels of error. To alleviate this problem, we propose an expert mapping system which utilizes the same inferences and mapping techniques used by expert human mappers to reduce the number of false maps found.

Algorithms↗
PubMed2004

Automated yeast two-hybrid screening for nuclear receptor-interacting proteins.

High throughput analysis of protein-protein interactions is an important sector of hypothesis-generating research. Using an improved and automated version of the yeast two-hybrid system, we completed a large interaction screening project with a focus on nuclear receptors and their cofactors. A total of 425 independent yeast two-hybrid cDNA library screens resulted in 6425 potential interacting protein fragments involved in 1613 different interaction pairs. We show that simple statistical parameters can be used to narrow down the data set to a high confidence set of 377 interaction pairs where validated interactions are enriched to 61% of all pairs. Within the high confidence set, there are 64 novel proteins potentially binding to nuclear receptors or their cofactors. We discuss several examples of high interest, and we expect that communication of this huge data set will help to complement our knowledge of the protein interaction repertoire of this family of transcription factors and instigate the characterization of the various novel candidate interactors.

Automation↗
PubMedDate not supplied

Topical cooling assisted hepatic resection of segment 7 and 8 oriented by en-bloc interruption of the targeted portal pedicles.

BACKGROUND/AIMS: The crucial points of hepatic segmentectomy include an accurate mapping of proposed segment(s) to be resected and minimization of intra-operative blood loss. This study reports a surgical technique of hepatic resection for segment 7 and 8, and a benefit of supplemental use of topical cooling during consecutive right hepatic inflow occlusion. METHODOLOGY: From January 1993 to December 1996, ten hepatocellular carcinoma patients with pathologic livers underwent hepatic segmentectomy for segment 7 and 8. The mapping of the target segments was guided by en-bloc test occlusion of the relevant portal pedicles and subsequent discoloration, often after the opening hilum method. Of these, five tumors were resected with topical cooling by ice slush seeding during consecutive right inflow occlusion (cooling group) and the remainder without cooling (Normothermic group). In the normothermic group, inflow occlusion was carried out by cyclic clamping and unclamping method. RESULTS: The inflow occlusion time was 54 +/- 9.4 min in the cooling group, much longer than in the normothermic group. Although the post-operative peak transaminase values were twice as high as those in the normothermic group, the blood loss was significantly less, and there was no detrimental effect of prolonged, consecutive ischemia on the other intra- and post-operative data. CONCLUSIONS: En-bloc taping of the target portal pedicles with or without the opening hilum method is useful in the mapping of segments, and the use of topical cooling is beneficial in prolonged inflow occlusion during complicated right-sided segmentectomy.

Adult↗
PubMed1998

Physical mapping of the mouse genome.

This review is intended to provide an overview of techniques and a source of reagents for physical mapping of the mouse genome. It focuses on those applications, methods, or resources unique to the mouse and on the generation of comparative physical maps. The reference list is not comprehensive; rather, recent reviews on each topic and selected representative examples are given.

Animals↗
PubMed2004

Brightening prospects for early cortical coding of perceived luminance: a high-density electrical mapping study.

Establishing the computational rules and neural substrates of brightness coding is a topic of both historical and contemporary interest. Two major classes of explanations for brightness illusions, such as brightness contrast, can be traced to Hering and Helmholtz. Hering's legacy is a low-level account in which brightness contrast results from obligatory lateral inhibitory interactions occurring at some level(s) in the visual system. Helmholtz offered a high-level account, positing a causal role for factors such as perceptual grouping, inferred illumination, and the extraction of surface properties such as orientation and reflectance. The tension between these theoretical viewpoints persists unabated to date. Intracranial electrophysiological recordings have revealed that brightness is represented in the firing rates of striate neurons, a fact consistent with low-level explanations. However, since the time-course of brightness-related responses relative to the onset of striate activity is undisclosed, it remains possible that striate activation might be temporally and causally secondary to higher-level computational processes. Knowledge of the timing of brightness-related neural activity is thus crucial to both constrain and adjudicate between these competing theories. We utilize high-density electrophysiological recording and a tachistoscopic brightness discrimination task to measure the time-course and scalp topography of brightness-related electrical potentials in human observers. Brightness perception is correlated with electrical activity at the earliest stages of visual cortical processing. These findings are interpreted to support Hering's low-level account of brightness for White's effect, and the results are discussed in the context of current theories of brightness perception.

Adult↗