Biomedical subjects

N Harvey

Publications and source records attributed to N Harvey.

At least 19 recordsLinked to original sources

PubMed2000

Using Advice and Assessing Its Quality.

People received advice from four sources and used it to produce a judgment. They also assessed the quality of advice by estimating the probability that it would be correct. They were better at assessing than at using advice: combinations of advice based on their assessments were superior to their judgments. Order of assessing and using advice, superficial differences between advisors, and using other methods of advice assessment had no significant effects on this superiority of advice assessment over advice use. However, use but not assessment was improved when some advisors exhibited biases opposite to those that people typically show. It appears that using advice imposes a heavier processing load than assessing its quality and that this load can be lightened by including advisors who exhibit unusual behavior. Their salience may help people working under a heavy processing load make appropriate pairings between advisor weights and advice. Copyright 2000 Academic Press.

Journal Article↗

PubMed1999

An encyclopedia of mouse genes.

The laboratory mouse is the premier model system for studies of mammalian development due to the powerful classical genetic analysis possible (see also the Jackson Laboratory web site, http://www.jax.org/) and the ever-expanding collection of molecular tools. To enhance the utility of the mouse system, we initiated a program to generate a large database of expressed sequence tags (ESTs) that can provide rapid access to genes. Of particular significance was the possibility that cDNA libraries could be prepared from very early stages of development, a situation unrealized in human EST projects. We report here the development of a comprehensive database of ESTs for the mouse. The project, initiated in March 1996, has focused on 5' end sequences from directionally cloned, oligo-dT primed cDNA libraries. As of 23 October 1998, 352,040 sequences had been generated, annotated and deposited in dbEST, where they comprised 93% of the total ESTs available for mouse. EST data are versatile and have been applied to gene identification, comparative sequence analysis, comparative gene mapping and candidate disease gene identification, genome sequence annotation, microarray development and the development of gene-based map resources.

Animals↗

PubMed1999

Nonpeptide endothelin receptor antagonists attenuate the pressor effect of diaspirin-crosslinked hemoglobin in rat.

Endothelin 1 (ET-1) is a potent vasoactive and mitogenic peptide that is thought to participate in the hemodynamic effects elicited by drugs that block the biosynthesis and release of endothelium-derived nitric oxide (NO), such as NO synthase inhibitors. Using the nonpeptide endothelin receptor antagonists bosentan and LU-135252, we tested the hypothesis that endothelins contribute to the pressor activity of diaspirin-crosslinked hemoglobin (DCLHb), a hemoglobin-based oxygen carrier, whose pressor activity in mammals is attributed primarily to a scavenging action towards NO. The NO synthase inhibitor nitro-L-arginine methyl ester (L-NAME), ET-1, and noradrenaline (NA) were used as reference drugs. Bosentan markedly reduced the pressor effects elicited by DCLHb, L-NAME, and ET-1, but not those evoked by NA. LU-135252 attenuated the pressor effect elicited by DCLHb and ET-1, but not that produced by L-NAME or NA. The decreases in heart rate associated with the pressor effect of DCLHb and L-NAME were reduced by LU-135252, whereas only those elicited by DCLHb were attenuated by bosentan. In contrast with bosentan, LU-135252 caused a decrease in the baseline blood pressure and heart rate. These results suggest that endothelins may participate in the pressor activity of DCLHb. They suggest also that nonpeptide endothelin receptor antagonists such as bosentan or LU-135252 may be useful to counteract endothelin-mediated undesirable hemodynamic effects of drugs that inhibit the activity of the NO system.

Animals↗

PubMed1998

Structural requirements and mechanism of the pressor activity of Leu-Val-Val-hemorphin-7, a fragment of hemoglobin beta-chain in rats.

A rat blood pressure assay was used to perform a structure-activity relationship study (SAR) of Leu-Val-Val-hemorphin-7 (LVV-H7), a fragment of hemoglobin (Hb) beta-chain, elucidate the mechanisms of its cardiovascular effects, and test its potential involvement in the pressor activity of diaspirin crosslinked Hb (DCLHb), a recently developed Hb-based oxygen carrier. The SAR study revealed that the C-terminal-Arg-Phe-amino acid sequence of LVV-H7 contained the main determinants of the pressor activity of this peptide. Drug interaction studies using various inhibitory drugs (e.g., phentolamine, clonidine, etc.) and LVV-H7 showed that the pressor effect and tachycardia elicited by LVV-H7 involved the activation of the sympathetic nervous system (SNS). Additional studies using phenytoin (sodium channel blocker), [Tic7]H7(5-7)-NH2 (putative antagonist of receptors for LVV-H7) and H7(5-7)-NH2, an amidated C-terminal fragment of LVV-H7, suggested that LVV-H7 activated the SNS by interacting with specific receptors functionally coupled with phenytoin-sensitive sodium channels. The pressor effect and tachycardia caused by LVV-H7 were potentiated by captopril, suggesting that the angiotensin converting enzyme may contribute to the inactivation of LVV-H7 in rats. The pressor activity of DCLHb, in contrast to that elicited by LVV-H7, was not affected by animal pretreatment with LVV-H7 fragments shown to inhibit the pressor effect of LVV-H7. We conclude that: 1) LVV-H7 is unlikely to mediate the pressor activity of DCLHb in rats; 2) the pressor and tachycardic activities of LVV-H7 are mediated by the SNS; 3) the C-terminal-Arg-Phe-amino acid sequence of LVV-H7 contains the chemical groups responsible for the pressor effect of this peptide in rats; 4) LVV-H7 and FMRF amide-related peptides may share the same mechanism of pressor activity in rats.

Animals↗

PubMed1997

Disease management: a continuum approach.

Disease management is a comprehensive, integrated approach to managing the health of populations through the use of disease-specific standards and protocols and population segmentation. It has been increasing in popularity among integrated delivery systems (IDSs) and payers alike as a way to respond to competitive pressures and to shift care delivery from inpatient to alternative care sites. To successfully implement disease-management programs, IDSs must develop an organizational mind-set that stresses information-driven, evidence-based standards of care that are adhered to across a tightly integrated continuum of care.

Continuity of Patient Care↗

PubMed1997

Disease management: program design, development, and implementation.

Disease management is an emerging approach to patient management, customer satisfaction, and cost containment that comprises disease modeling; patient segmentation and risk assessment; clinical protocols; and wellness, self-management, and education. Implementing a disease management program poses significant challenges to healthcare organizations. To successfully implement a disease management program, a tightly integrated continuum of care, sophisticated information systems, and disease management support systems must be in place. Strategic partnerships with outside vendors may speed program implementation and provide opportunities to develop risk-sharing relationships.

Costs and Cost Analysis↗

PubMed1997

A new guide to EMC.

The European Commission has now finalized its new guide to the application of the Electromagnetic Compatibility Directive. The document makes significant changes in emphasis and substance to current thinking. This article describes the key changes relating to issues such as components, installations and systems, and the implications for suppliers of medical devices.

Electromagnetic Fields↗

PubMed1995

Development of a binding assay for the B1 receptors for kinins.

A novel binding assay to kinin B1 receptors was developed, based on the design of a high-affinity agonist ligand, [125I]Tyr-Gly-Lys-Aca-Lys-des-Arg9-BK. Binding to rabbit aortic smooth muscle cells is highly temperature-dependent (optimal at 37 degrees C); apparent binding equilibrium is reached within 30 min, and competition by kinin analogs reveals the expected correlation with the B1 receptor pharmacology. The dissociation constant (Kd) of the labeled ligand is approx. 0.2 nM and this value does not change significantly as a function of cytokine pretreatment. However, the receptor abundance (Bmax) is significantly increased (1.5-fold) by pretreating the cells with interleukin-1 (IL-1), while oncostatin M (OSM) produces a marginal increase of the Bmax. This assay may be useful in documenting the regulation of B1 receptors in pathology.

Amino Acid Sequence↗

PubMed1995

Asthma in Jemez Pueblo schoolchildren.

Asthma, a major chronic health problem of children, has received little investigation in Native Americans. We conducted a survey of asthma in children of Jemez Pueblo, Jemez, New Mexico, in response to concerns of the community and health care providers about the frequency of asthma. In collaboration with Jemez Pueblo, we developed a standardized questionnaire and administered it to parents of 318 children aged 3 to 13 years. Parents reported that 12.3% had been diagnosed as having asthma or reactive airway disease by a physician or other health care practitioner. Asthma was reported as still active at the time of the interview for 55% of those subjects. The study showed that asthma was not uncommon among the Jemez Pueblo children and, in fact, was more common than in recent nationwide surveys.

Adolescent↗

PubMed1993

Lymphocyte aging in bone marrow chimeras.

Chimeric mice provide a unique approach to the analysis of genetic factors associated with aging since cells with two genetically distinct backgrounds can be analyzed in the same animal. In this study, bone marrow chimeras were produced by reconstituting lethally irradiated female B6AF1 [(C57BL/6 female x A male)F1] mice with varying mixtures of T cell-depleted bone marrow cells from A (short-lived) and C57BL/6 (long-lived) mice. The phenotypic composition of the peripheral blood lymphocytes was analyzed using either a cytotoxicity assay or flow cytometry with indirect immunofluorescence. The percentage of A-derived lymphocytes in the peripheral blood following reconstitution was generally higher than the percentage of A bone marrow cells with which the irradiated mice were inoculated, suggesting that the cells from the A donor bone marrow were more efficient at marrow reconstitution than the cells from the C57BL/6 donor bone marrow. In order to determine whether the percentage of A- versus C57BL/6-derived cells changed with age in each animal, the chimeric mice were bled for phenotype analysis of peripheral blood lymphocytes between 2-6 months following reconstitution and at 2-3 month intervals until death. For most animals [93/127 (73%)], there was no consistent pattern of increase or decrease (> 20%) with regard to the percentage of A lymphocytes in the peripheral blood over time. However, in 34/127 (27%) of the chimeras, a change greater than 20% in the phenotypic composition of the peripheral blood lymphocytes was observed and these animals were considered unstable. Among these 34 unstable animals, 6 (18%) showed an overall increase in A-derived lymphocytes, 24 (71%) showed an overall decrease in A-derived lymphocytes, and 4 (12%) showed fluctuating increases and decreases over their lifespan. While the lifespans of the chimeric animals in these studies were considerably shorter than those reported for untreated mice of the same strain and gender, in these animals increased proportions of A cells were associated with significantly longer lifespans. In addition, the lifespan of the B6AF1 chimeric mice was a function of the proportion of A lymphocytes present in the peripheral blood over the course of the animal's life.

Animals↗

PubMed1992

Renal Na(+)-phosphate cotransport in X-linked Hyp mice responds appropriately to Na+ gradient, membrane potential, and pH.

To investigate the mechanism for the 50% decrease in Vmax of the high-affinity phosphate transport system in the renal brush-border membrane of X-linked Hyp mice, we compared the effects of external Na+ concentration, membrane potential, pH, phosphonoformic acid (PFA), and arsenate on Na(+)-Pi cotransport in brush-border membrane vesicles prepared from normal mice and Hyp littermates. The affinity of the Na(+)-Pi cotransport system for Na+ (apparent Km = 60 +/- 7 and 64 +/- 2 mM for normal and Hyp mice, respectively) and the Na(+)-Pi stoichiometry estimated from Hill plots (2.5 +/- 0.2 and 2.9 +/- 0.6 for normal and Hyp mice, respectively) were similar in brush-border membranes of both strains. Inside-negative membrane potential, generated by anions of different permeabilities, stimulated Na(+)-Pi cotransport and inside-positive membrane potential generated by valinomycin, and a K+ gradient (outside greater than inside) inhibited Na(+)-Pi cotransport to the same extent in brush-border membranes derived from normal mice and Hyp littermates. The pH dependence of Na(+)-Pi cotransport was similar in brush-border membrane vesicles of normal and Hyp mice. The ratio of Na(+)-Pi cotransport measured at pH 7.5 relative to that at pH 6.5 was 2.9 +/- 0.6 in normal mice and 2.9 +/- 0.7 in Hyp mice. PFA was a competitive inhibitor of Na(+)-Pi cotransport in brush-border membranes of both normal and Hyp mice. However, the apparent Ki for PFA was significantly lower in Hyp mice (0.31 +/- 0.01 and 0.19 +/- 0.02 mM in normal and Hyp mice, respectively, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Wishful thinking impairs belief-desire reasoning: a case of decoupling failure in adults?

Subjects were presented with a scenario that described how a certain type of opinion poll can be manipulated by respondents to put one particular political party (the threatened party) at a disadvantage. In a first experiment, people supporting this party but pretending to oppose it were found to be as likely to say that they would manipulate the poll as people who actually opposed it. In a second experiment, the threat embodied in the scenario was made more direct. It was also more salient because the study was carried out at a time of heightened political awareness when supporters of the threatened party were genuinely concerned about its future. People supporting the threatened party but pretending to oppose it were now about half as likely to say that they would manipulate the poll as those who actually opposed it. Two explanations for this breakdown in the belief-desire reasoning subserving pretense are considered.

Adolescent↗

PubMed1991

Renal brush-border membrane Na(+)-sulfate cotransport: stimulation by thyroid hormone.

The present study was undertaken to examine the interaction of phosphonoformic acid (PFA) with the Na(+)-sulfate cotransporter and the effect of thyroid hormone (triiodothyronine; T3) on Na(+)-dependent sulfate transport and Na(+)-dependent PFA binding in mouse renal brush-border membrane vesicles. PFA inhibits Na(+)-dependent sulfate transport in a competitive manner [apparent inhibitory constant (Ki) = 4.3 +/- 1.1 mM]. T3 administered in pharmacological doses significantly stimulates Na(+)-dependent sulfate transport in renal brush-border membranes compared with vehicle-treated controls. Although T3 has no effect on Na(+)-dependent glucose transport, T3 also stimulates Na(+)-dependent phosphate transport. Kinetic studies demonstrate that T3 increases the apparent maximal velocity (Vmax) for Na(+)-sulfate cotransport without changing the apparent Michaelis constant (Km). T3 does not significantly affect either Na(+)-dependent PFA binding or the phosphate- and sulfate-displaceable components of Na(+)-dependent PFA binding. Finally, Na(+)-dependent brush-border membrane sulfate transport is unchanged in phosphate-deprived mice that exhibit increased Na(+)-phosphate cotransport and in X-linked Hyp mice that exhibit impaired Na(+)-phosphate cotransport. The present results demonstrate that 1) PFA is a competitive inhibitor of Na(+)-sulfate cotransport, 2) T3 stimulates Na(+)-dependent sulfate, as well as Na(+)-dependent phosphate transport, but has no effect on PFA binding, and 3) phosphate deprivation and the X-linked Hyp mutation do not influence Na(+)-sulfate cotransport.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Major histocompatibility complex antigen expression on lymphocytes from aging strain A mice.

Molecules encoded by the major histocompatibility complex (MHC) are crucial for the proper functioning of the immune response. In this study, the levels of class I and class II major histocompatibility antigens on lymphocytes from strain A mice were measured as a function of age. Class I protein levels increased significantly on both peripheral blood and spleen (T cells and B cells) lymphocytes with age. This increase in MHC class I protein levels was accompanied by an increase in class I mRNA levels. On the other hand, class II protein levels did not show a significant change with age. Moreover, while the percentage of class I-expressing spleen lymphocytes stayed at a steady-state level of 100% with age, the percentage of class II-expressing spleen lymphocytes decreased from 85% in young animals to 70% in old animals. This decrease was due to a decrease in the relative proportion of B cells compared to T cells in the spleen lymphocyte population of old mice. When class II mRNA levels were measured, it was found that these levels decreased markedly with age. Overall, it is clear that the regulation of MHC class I and class II expression changes with age in A strain mice. Since optimal levels of MHC expression are crucial for the proper functioning of cellular and humoral immune responses, it will be most interesting to understand how the control of MHC gene expression changes with age and whether MHC gene expression can be modulated in old individuals to restore better immune function.

Aging↗

PubMed1990

Normal molecular size of the Na(+)-phosphate cotransporter and normal Na(+)-dependent binding of phosphonoformic acid in renal brush border membranes of X-linked Hyp mice.

X-linked Hyp mice have a specific defect in Na(+)-dependent phosphate (Pi) transport at the renal brush border membrane (BBM). In the present study we examined the effect of the Hyp mutation on the molecular size of the Pi transporting unit and on Na(+)-dependent 14C-phosphonoformic (PFA) binding in renal BBM vesicles. By radiation inactivation analysis, we demonstrated that the molecular size of the Na(+)-Pi cotransporter is similar in normal (242 +/- 16 kDa) and Hyp mice (227 +/- 39 kDa). Moreover, while BBM Na(+)-dependent Pi transport is significantly reduced in Hyp mice (249 +/- 54 vs 465 +/- 82 pmol/mg protein/6s), genotype differences in (1) Na(+)-dependent PFA binding (1020 +/- 115 vs 1009 +/- 97 pmol/mg protein/30 min), (2) Pi-displaceable Na(+)-dependent PFA binding (605 +/- 82 vs 624 +/- 65 pmol/mg protein/6s), and (3) phosphate uptake at Na(+)-equilibrium (67 +/- 10 vs 54 +/- 7 pmol/mg protein/6s) are not apparent. The present data demonstrate that the molecular size of the renal BBM Na(+)-Pi cotransporter is normal in Hyp mice and suggest that the number of Na(+)-Pi cotransporters may not be reduced in the mutant strain.

Animals↗

PubMed1988

The 'worried well'.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗

PubMed1988

Stereoselective recognition in phospholipid monolayers.

During the past ten years we have investigated the stereochemistry of intermolecular interactions in monolayers at the air-water interface, a field which has never been developed explicitly before to our knowledge. Although we demonstrated clear enantiomeric and diastereomeric interactions for a number of chiral surfactants, we found no evidence whatsoever for stereoselective interaction in dipalmitoylphosphatidylcholine (DPPC) monolayers or vesicles by standard monolayer techniques, differential scanning calorimetry or ultra-highfield NMR. The present article extends these observations to dimyristoyl- and dilauroylphosphatidylcholine. Results from dynamic surface tension studies are also reported. In no case could chiral recognition be demonstrated using the 95% confidence limit as the criterion. In our previous study of DPPC mixtures with another chiral surfactant the question arose as to whether chiral interactions could be transmitted through intervening phospholipid molecules. This question is addressed by examining the force-area curves for a variety of mixed monolayers composed of chiral surfactants and phospholipids. We conclude that the chiral discrimination observed in some of these mixed monolayers is due to the direct interaction of chiral centers, and not due to the transmission of chirality from one stereocenter to the next through intermediate achiral molecules. Finally, we will consider the question of why phospholipids, the most ubiquitous of natural chiral surfactants, should show so little chiral discrimination in view of the wide occurrence of high stereoselectivity in many natural processes.

Dimyristoylphosphatidylcholine↗

PubMed1986

No phospholipid monolayer-sugar interactions.

Studies by a number of workers using the Langmuir film balance have shown that when carbohydrates, such as sucrose or glycerol, are dissolved in a subphase on which a phospholipid is spread, film expansion occurs (Cadenhead & Demchak, 1969; Cadenhead & Bean, 1972; Maggio et al., 1976; Maggio & Lucy, 1978). Recently such effects have been observed again, particularly with the carbohydrates galactose and trehalose (Johnston et al., 1984). The origin of these film expansions was uncertain, and various suggestions have been made to explain them. One idea was that they might be due to interactions which these carbohydrates have with the water molecules close to the polar head groups of the lipids. Recent studies in our two laboratories, described here, show that the magnitude of the expansion effects is variable and that in general they arise from surfactant impurities in the sugars. These impurities are observed in carbohydrates which are reputedly of high grade; the amount of impurity present can vary from batch to batch, and sometimes they can be difficult to remove. Film balance techniques or subphase preparation can mask the detection of minor impurities. The presence of surfactant impurities in reputedly pure carbohydrates needs to be considered in other biochemical and biophysical studies of lipids and cell membranes.

Carbohydrates↗