Search PubMed⌕ Search

Biomedical subjects

J M White

Publications and source records attributed to J M White.

At least 145 records · Page 8Linked to original sources
PubMed1995

The renin angiotensin system and nociception in spontaneously hypertensive rats.

This study investigated the effects of captopril, hydralazine and losartan on the locomotor activity, tailflick and hot plate latencies in spontaneously hypertensive rats (SHR) and their genetic controls the Wistar-Kyoto rat (WKY). The increased hot plate latencies normally exhibited by the spontaneously hypertensive rat were reduced or abolished by captopril (95 mg/kg/day p.o.) and losartan (18 mg/kg/day p.o.) treatment, but were unaffected by hydralazine (19 mg/kg/day p.o.). There were no observable effects of any of the drugs on tailflick latencies or locomotor activity. The results highlight a potential role for angiotensin II in analgesia that is independent of blood pressure change.

Angiotensin Receptor Antagonists↗
PubMed1995

ADAM, a widely distributed and developmentally regulated gene family encoding membrane proteins with a disintegrin and metalloprotease domain.

Fertilin alpha and beta, previously known as PH-30 alpha and beta, are two subunits of a guinea pig sperm integral membrane protein implicated in sperm-egg binding and fusion. They are derived from sequence-similar precursors which contain a metalloprotease-like and a disintegrin-like domain and which are related to a family of metalloprotease and disintegrin domain-containing snake venom proteins. We report here the cloning, sequencing, and characterization of mouse fertilin alpha and beta as well as five additional sequence-similar cDNAs from guinea pig and mouse testis. We name this gene family ADAM, for proteins containing A Disintegrin And Metalloprotease domain, and in honor of its dual origins in the fields of snakes and fertility. In situ hybridization demonstrated that, in testis, RNA encoding these ADAMs is expressed only in spermatogenic cells and that this expression is developmentally regulated. PCR analysis of mouse tissue cDNA showed that these ADAMs display different patterns of tissue distribution. Some ADAMs (e.g., fertilin alpha) have the consensus active-site sequence for a zinc-dependent metalloprotease in their metalloprotease-like domain. All have a disintegrin-like domain, which could bind integrins or other receptors. Some have sequences which may be active in membrane fusion. All encode potential membrane-spanning domains. Searches of sequence databases revealed that additional mammalian members of the ADAM gene family have been cloned from a variety of tissues. Thus, the ADAMs are a large, widely expressed, and developmentally regulated family of proteins with multiple potential functions in cell-cell and cell-matrix interactions.

ADAM Proteins↗
PubMed1995

Accommodation in humans with juvenile macular degeneration.

Accommodation, or the change in refractive power of the eye to focus objects at different distances, is driven by many stimuli including defocus blur, the awareness of target distance or proximal cues, and through the vergence crosslink (convergence accommodation). The effectiveness of defocus blur as an accommodative stimulus is decreased in normally-sighted subjects as visual acuity is experimentally reduced and as the target is imaged at increasing eccentricities from the fovea. Since subjects with central retinal abnormalities have reduced visual acuity and typically fixate eccentrically, one would predict that defocus blur would not be an effective accommodative stimulus for them. Using an infrared optometer, steady-state accommodative responses of six subjects with juvenile macular degeneration (JMD) and of three normally-sighted controls were measured. The effectiveness of defocus blur in stimulating accommodation varied across the subjects and was related to visual acuity, with those subjects having worse acuity showing less accurate accommodative responses. When provided with additional cues to accommodative demand (i.e. proximal and/or binocular cues), subjects with JMD showed more accurate accommodative responses. In general, those subjects who did not modulate accommodative response with changing defocus blur cues showed the most accurate accommodation under binocular viewing. In contrast, those subjects who did change accommodative response with changing defocus blur cues showed the most accurate accommodation under monocular viewing.

Accommodation, Ocular↗
PubMed1995

Characterization of GABAB ligands in vivo.

1. While GABAB antagonists have been examined in vitro, very few have been tested in vivo. A range of GABAB antagonists were tested against baclofen-induced muscle relaxation and hypothermia. 2. The GABAB antagonists exhibited a range of in vivo activity profiles. 3. CGP 35348 showed clear antagonist effects, while BPBA and 4-ABPA appeared to have agonist properties. 4. Phaclofen, 2-hydroxysaclofen, 3-APPA and 9G seemed to have little effect in this system at the doses tested. 5. Differences between in vivo and in vitro activity could be explained by differences in blood-brain barrier permeability, or possible differences in affinities for the sub-classes of GABAB receptors.

Animals↗
PubMed1995

GPI-anchored influenza hemagglutinin induces hemifusion to both red blood cell and planar bilayer membranes.

Under fusogenic conditions, fluorescent dye redistributed from the outer monolayer leaflet of red blood cells (RBCs) to cells expressing glycophosphatidylinositol-anchored influenza virus hemagglutinin (GPI-HA) without transfer of aqueous dye. This suggests that hemifusion, but not full fusion, occurred (Kemble, G. W., T. Danieli, and J. M. White. 1994. Cell. 76:383-391). We extended the evidence for hemifusion by labeling the inner monolayer leaflets of RBCs with FM4-64 and observing that these inner leaflets did not become continuous with GPI-HA-expressing cells. The region of hemifusion-separated aqueous contents, the hemifusion diaphragm, appeared to be extended and was long-lived. But when RBCs hemifused to GPI-HA-expressing cells were osmotically swollen, some diaphragms were disrupted, and spread of both inner leaflet and aqueous dyes was observed. This was characteristic of full fusion: inner leaflet and aqueous probes spread to cells expressing wild-type HA (wt-HA). By simultaneous video fluorescence microscopy and time-resolved electrical admittance measurements, we rigorously demonstrated that GPI-HA-expressing cells hemifuse to planar bilayer membranes: lipid continuity was established without formation of fusion pores. The hemifusion area became large. In contrast, for cells expressing wt-HA, before lipid dye spread, fusion pores were always observed, establishing that full fusion occurred. We present an elastic coupling model in which the ectodomain of wt-HA induces hemifusion and the transmembrane domain, absent in the GPI-HA-expressing cells, mediates full fusion.

Animals↗
PubMed1995

Receptor-induced conformational changes in the subgroup A avian leukosis and sarcoma virus envelope glycoprotein.

We recently reported that Tva, the host cell receptor for subgroup A avian leukosis and sarcoma viruses, binds specifically to the subgroup A envelope glycoprotein (Env-A) (J.M. Gilbert, P. Bates, H. E. Varmus, and J. M. White, J. Virol. 68:5623-5628, 1994). Here we have tested the hypothesis that binding of Tva causes conformational changes in Env-A that correlate with its conversion from a fusion-inactive to a fusion-active state. Conformational changes were examined by both a proteolysis and an immunoprecipitation assay. A temperature-dependent conformational change, demonstrated by the generation of a specific thermolysin digestion product of the surface (SU) subunit, occurred when a soluble form of Tva (sTva) was incubated with Env-A. sTva did not induce this conformational change in Env-C or in a noninfectious precursor form of Env-A, Env-A CL. However sTva did induce the conformational change in Env-A CL that had been pretreated in vitro to produce the SU and transmembrane (TM) subunits. Moreover, interaction of Tva with Env-A at 25 degrees C, but not at 4 degrees C, appeared to reveal a previously buried segment of the putative fusion peptide of Env-A. Our results suggest that binding of Tva to Env-A results in specific conformational changes in the Env-A glycoprotein that are relevant to the activation of its fusion function.

3T3 Cells↗
PubMed1995

Models and processes of research utilization.

The proliferation of research in nursing is greater today than at any other time in the history of nursing. In order for this research to be meaningful for practice, research utilization efforts are imperative. This article reviews three prominent research utilization models spanning three decades of development. Future challenges and suggestions for improving the process are identified. Through research utilization efforts, nurses are given the power to make informed choices regarding implementation of research-based assessments, diagnoses, interventions, and outcome measures that ultimately will result in improved patient outcomes.

Clinical Nursing Research↗
PubMed1994

IgE-dependent IL-4 secretion by human basophils. The relationship between cytokine production and histamine release in mixed leukocyte cultures.

IL-4 protein and mRNA have recently been detected in pure basophil cultures after stimulation. It has also been established in mixed leukocyte cultures obtained by elutriation and challenged with anti-IgE that the basophil is the only cell that makes detectable IL-4. We have used cells prepared using Percoll gradients (5 to 30% basophils) to study the relationship between histamine release and IL-4 synthesis. In cultures challenged with anti-IgE after a 15-min pretreatment with IL-3, detectable IL-4 secretion ranged from 40 to 630 pg/10(6) basophils in 18 of 22 donors, with no significant correlation (r = 0.21, p = 0.34) with basophil purity. IL-4 synthesis was dissociated from histamine release, with optimal production consistently occurring at 10 ng/ml anti-IgE, whereas histamine levels peaked at 50 to 100 ng/ml of stimulus. Stimulation with anti-IgE alone was sufficient for IL-4 secretion but protein levels were enhanced two- to threefold in low responders by increasing the calcium concentration to 5 mM with no significant changes in histamine release. The IgE-independent secretagogues, F-met peptide (1 microM) and C5a (25 ng/ml), demonstrated limited ability to generate detectable IL-4, despite promoting vigorous histamine release. Additional studies showed no significant difference between IL-4 secretion in atopic and nonatopic donors. Finally, IL-4 levels generated with specific Ags were comparable to those levels produced in response to anti-IgE. We predict that basophil IL-4 generation will have a proinflammatory effect, but it appears that the signal transduction mechanisms for its synthesis and release differ from those for histamine release and thus may require different methods of pharmacologic control.

Basophils↗
PubMed1994

Identification of a binding site in the disintegrin domain of fertilin required for sperm-egg fusion.

Fertilization and certain later stages in mammalian embryonic development require fusion between membranes of individual cells. The mechanism of eukaryotic cell-cell fusion is unknown, and no surface molecules required for this process have been unequivocally identified. The role of the sperm surface protein fertilin in sperm-egg fusion was tested by using peptide analogues of a potential integrin binding site in the fertilin beta subunit. Peptide analogues that include a TDE sequence from the disintegrin region of fertilin beta are able to bind to the egg plasma membrane and strongly inhibit sperm-egg fusion. These results show that the disintegrin domain of fertilin beta binds to the egg plasma membrane and that this binding is required for membrane fusion.

ADAM Proteins↗