PubMed Health⌕ Search

Biomedical subjects

J Winslow

Publications and source records attributed to J Winslow.

At least 19 recordsLinked to original sources
PubMed2004

The Mouse Genome Database (MGD): integrating biology with the genome.

The Mouse Genome Database (MGD) is one component of the Mouse Genome Informatics (MGI) system (http://www.informatics.jax.org), a community database resource for the laboratory mouse. MGD strives to provide a comprehensive knowledgebase about the mouse with experiments and data annotated from both literature and online sources. MGD curates and presents consensus and experimental data representations of genetic, genotype (sequence) and phenotype information including highly detailed reports about genes and gene products. Primary foci of integration are through representations of relationships between genes, sequences and phenotypes. MGD collaborates with other bioinformatics groups to curate a definitive set of information about the laboratory mouse and to build and implement the data and semantic standards that are essential for comparative genome analysis. Recent developments in MGD discussed here include an extensive integration of the mouse sequence data and substantial revisions in the presentation, query and visualization of sequence data.

Animals↗
PubMed1999

Regulation of learning by EphA receptors: a protein targeting study.

EphA family receptor tyrosine kinases and their ephrin-A ligands are involved in patterning axonal connections during brain development, but until now a role for these molecules in the mature brain had not been elucidated. Here, we show that both the EphA5 receptor and its ephrin-A ligands (2 and 5) are expressed in the adult mouse hippocampus, and the EphA5 protein is present in a phosphorylated form. Because there are no pharmacological agents available for EphA receptors, we designed recombinant immunoadhesins that specifically bind to the receptor binding site of the ephrin-A ligand (antagonist) or the ligand binding site of the EphA receptor (agonist) and thus target EphA function. We demonstrate that intrahippocampal infusion of an EphA antagonist immunoadhesin leads to impaired performance in two behavioral paradigms, T-maze spontaneous alternation and context-dependent fear conditioning, sensitive to hippocampal function, whereas activation of EphA by infusion of an agonist immunoadhesin results in enhanced performance on these tasks. Because the two behavioral tasks have different motivational, perceptual, and motor requirements, we infer the changes were not caused by these performance factors but rather to cognitive alterations. We also find bidirectional changes in gene expression and in electrophysiological measures of synaptic efficacy that correlate with the behavioral results. Thus, EphA receptors and their ligands are implicated as mediators of plasticity in the adult mammalian brain.

Animals↗
PubMed1998

Intense sub-kilometer-scale boundary layer rolls observed in hurricane fran

High-resolution observations obtained with the Doppler On Wheels (DOW) mobile weather radar near the point of landfall of hurricane Fran (1996) revealed the existence of intense, sub-kilometer-scale, boundary layer rolls that strongly modulated the near-surface wind speed. It is proposed that these structures are one cause of geographically varying surface damage patterns that have been observed after some landfalling hurricanes and that they cause much of the observed gustiness, bringing high-velocity air from aloft to the lowest observable levels. High-resolution DOW radar observations are contrasted with lower-resolution observations obtained with an operational weather radar, which underestimated peak low-level wind speeds.

Journal Article↗
PubMed1997

NGF binding to p75 enhances the sensitivity of sensory and sympathetic neurons to NGF at different stages of development.

To clarify the role of the common neurotrophin receptor p75 in modulating the survival response of sensory and sympathetic neurons to NGF at different stages of development, we compared the actions of wild-type NGF with a mutated NGF protein that binds normally to TrkA, the NGF receptor tyrosine kinase, but has greatly reduced binding to p75. At saturating concentrations, the NGF mutant promoted the survival of similar numbers of trigeminal sensory and sympathetic neurons as NGF. At subsaturating concentrations, the NGF mutant was less effective than wild-type NGF in promoting the survival of embryonic sensory neurons and postnatal sympathetic neurons but was equally effective as wild-type NGF in promoting the survival of embryonic sympathetic neurons. Whereas the levels of trkA and p75 were similar in embryonic sensory neurons and postnatal sympathetic neurons, the level of p75 was significantly lower than that of trkA in embryonic sympathetic neurons. These results indicate that binding of NGF to p75 enhances the sensitivity of NGF-dependent neurons to NGF at stages in their development when the levels of p75 and TrkA are similar.

Animals↗
PubMed1995

Comparison of cardiac output measurements by thermodilution and thoracic electrical bioimpedance in critically ill versus non-critically ill patients.

Thoracic electrical bioimpedance (TEB) has been proposed as an alternative to thermodilution (TD) for the measurement of cardiac output in settings such as the Emergency Department where invasive monitoring is not available. Validation studies comparing TEB with TD suggest a wide range of variability in the agreement between the two methods. This prospective study tests the hypothesis that this variability may be related to the severity of patient illness. Fifteen non-critically ill patients undergoing cardiac catheterization and 13 critically ill patients who underwent Swan-Ganz catheterization in the medical intensive care unit (MICU) were enrolled. Fifty-one pairs of data from the catheterization laboratory and 49 pairs of data from the MICU were obtained. The patients were graded retrospectively according to the APACHE II scoring system. The mean difference (bias) between TEB and TD results was calculated for each patient using the method suggested by Bland and Altman. A pooled t-test was performed to determine whether there was any significant difference between the APACHE II scores or cardiac output measurements obtained by TEB and TD in the two groups. APACHE II scores were 4.7 +/- 1.2 for the catheterization laboratory and 14.2 +/- 5.0 for the intensive care unit patients (P < .001). The catheterization laboratory (cath lab) group bias was 0.23 +/- 2.19, whereas the MICU bias was .002 +/- 2.33. There was no significant difference in the bias between the two groups despite significant differences in the APACHE II scores. Standard deviations of the bias were less than 15% different from each other.(ABSTRACT TRUNCATED AT 250 WORDS)

APACHE↗
PubMed1995

Patellofemoral pain in female ballet dancers: correlation with iliotibial band tightness and tibial external rotation.

Review of the literature reveals that ballet dancers have a high incidence of idiopathic patellofemoral pain. Twenty-four female ballet dancers were subjects in a study of the relationship between: 1) iliotibial band (ITB) tightness and patellofemoral pain, and 2) ITB tightness and degrees of tibial external rotation used in the dance demi-plie. Dancers were initially assessed by questionnaire to determine if any had knee pain. Twelve subjects met the study criteria for patellofemoral pain, and 12 dancers without knee pain served as controls for the study, Iliotibial band tightness was measured (Ober test), and degrees of tibial external rotation used during knee flexion (demi-plie) in standing were measured in both legs of all 24 subjects (48 legs). Chi-square analysis of the collected data revealed that there was an association between ITB tightness and patellofemoral pain in the dancers. Data analysis using the Wilcoxon Rank Sum test revealed that the degree of tibial external rotation used by dancers with iliotibial band tightness was significantly greater than those without ITB tightness. This study confirms the assumption that ITB tightness in dancers may be a contributing factor to patellofemoral pain. Follow-up study is indicated to determine if the preservation or restoration of functional ITB length is effective in the prevention and/or treatment of patellofemoral pain in ballet dancers.

Adult↗
PubMed1991

Vasopressin modulates male squirrel monkeys' behavior during social separation.

The central administration of arginine-vasopressin (AVP) in rodents has been associated with the modulation of a number of categories of behavior including social recognition and learning, aggression, grooming, and feeding. Concentrations of AVP in brain have also been functionally related to gonadal steroid hormone manipulations. In the current experiments we investigated the behavioral effects of centrally administered AVP on the behavior of pair-housed male squirrel monkeys during brief social separations. Prior to treatment, pairs of male squirrel monkeys established reliable and persistent dominance relationships measured as different patterns of social behavior and plasma levels of testosterone. Central administration of AVP increased scent-marking and grooming behaviors during the social separation test, however these effects were not influenced by the social status of the treated monkey. The effects of AVP on these measures were not mimicked by doses of oxytocin (OT). Both AVP and OT decreased the frequency of vigilance-checking and 'isolation-peep' calls. The data are consistent with a facilitatory role for AVP in the stress response and also suggest that these particular effects are not influenced by differences in testosterone associated with social dominance.

Analysis of Variance↗
PubMed1991

A new computer-assisted three-dimensional reconstruction method provides accurate measurement of glomerular mesangial volume.

Many glomerulopathies are characterized by progressive mesangial (interstitial) expansion which can be quantitated by morphometric analysis. The purpose of this study was to analyze mesangial and glomerular volumes using a new computer-assisted reconstruction (CAR) method. CAR was compared to two standard planar methods, point-counting and linear integration, for accuracy and time efficiency. In Phase I of the study, a computer-based model of the mesangial space was created by placing spherical and ellipsoidal objects of known volume into an enclosing volume mimicking the glomerulus. The simulated mesangium occupied approximately 10 percent of the glomerular volume. The model glomerulus was sectioned serially into ten sections of equal thickness and the three morphometric methods applied to determine the mesangial/glomerular volume. The complexity of the mesangial model was varied by increasing the number of mesangial regions from one to ten to 100. The CAR method estimated the model mesangial volume more accurately (1-9 percent error) through each level of complexity compared to point-counting (3-17 percent error) and linear integration (3-18 percent error). The point-counting method consistently overestimated (P less than 0.05) the fractional mesangial volume for the ten- and 100-region mesangium models. In Phase II of the study, a normal rat glomerulus was sectioned serially (215 sections) and a transmission electron micrograph (TEM) of every fifth section (n = 43) was obtained. Each TEM image (2% of glomerular surface) was digitized for analysis by CAR. Point-counting and linear integration were also performed on the whole glomerular TEMs (n = 10, randomly chosen). The estimated relative mesangial/glomerular volume was 6.6 +/- 0.1 percent by CAR (mean +/- SD), 9.7 +/- 1.5 by linear integration, and 14.9 +/- 3.4 by point-counting. The point-counting method was most efficient, requiring 40 +/- 8 sec/section, followed by CAR at 85 +/- 24 sec/section. Linear integration was least efficient (93 +/- 23 sec/section). We conclude that CAR is the most accurate morphometric method of the three compared for estimating mesangial and glomerular methods, although it is more time consuming than the point-counting method and requires more complex instrumentation. CAR is the only method that will analyze the shape and three-dimensional complexity of glomerular structures using TEMs.

Animals↗
PubMed1991

The pharmacokinetics and metabolism of human relaxins in rhesus monkeys.

Two forms of chemically synthesized human relaxin (rHlx and hRlx-2) were administered as 88 micrograms/kg intravenous bolus doses to pregnant and nonpregnant rhesus monkeys. No significant differences in pharmacokinetics were observed between pregnant and nonpregnant animals for either form of relaxin; however, clearance of hRlx (3.1-3.4 ml/min/kg) was significantly slower than clearance of hRlx-2 (6.2-6.5 ml/min/kg) in both pregnant and nonpregnant animals. Although the terminal half-lives for hRlx and hRlx-2 were similar (148-157 min), the initial and steady-state volumes of distribution were somewhat larger for hRlx-2 (71-85 and 398-418 ml/kg, respectively) than for hRlx (61-65 and 294-319 ml/kg, respectively). The metabolism of hRlx-2 was also investigated in pregnant and non-pregnant rhesus monkeys after iv bolus (0.44 mg/kg) or 60-min infusion (1.1 mg/kg) administration. Fast atom bombardment mass spectral analysis of the relaxin immunoreactivity isolated from the plasma indicated that hRlx-2 was partially degraded by removal of amino acids from the C terminus of the B chain. The percentage of intact material declined over a 60-min time course. At 60 min post-dose, intact hRlx-2 was approximately 46-64% of the detected material. Degraded forms representing loss of one and four amino acids (hRlx) from the C terminus of the B chain were approximately 11-13 and approximately 19-34% of the detectable material, respectively.

Animals↗
PubMed1990

Equine herpesvirus type 1 unique short fragment encodes glycoproteins with homology to herpes simplex virus type 1 gD, gI and gE.

The nucleotide sequence of a 6.4 kbp portion of the 10.6 kbp BamHI fragment D contained in the unique short region of the equine herpesvirus type 1 (EHV-1) genome has been determined. Analysis of this sequence revealed five open reading frames (ORFs), four complete and one incomplete, which were encoded by the same sense strand. Comparison of the EHV-1 DNA sequence with that encoding glycoproteins of other alphaherpesviruses has revealed no significant homologies. Comparison at the amino acid level, however, has demonstrated regions of significant sequence similarity between the three complete EHV-1 ORFs 2, 3 and 4, and the herpes simplex virus type 1 (HSV-1) glycoprotein gD encoded by the US6 gene, the HSV-1 glycoprotein gI encoded by the US7 gene and the HSV-1 glycoprotein gE encoded by the US8 gene, respectively. The interrupted ORF 5 was found to display partial homology with the HSV-1 US9-encoded protein, but no homology was found between the protein encoded by ORF 1 and other proteins. The three collinear EHV-1 ORFs encoding putative glycoproteins with homology to the HSV-1 glycoproteins were therefore designated EHV-1 gD, gI and gE, respectively. Moreover, further similarities were found between EHV-1 gD and pseudorabies virus (PRV) gp50, between EHV-1 gI and PRV gp63 and varicellazoster virus (VZV) gpIV, and between EHV-1 gE and PRV gI and VZV gpI. It is concluded that EHV-1, PRV, HSV-1 and VZV encode homologous glycoprotein genes in the small unique components of their genomes and that the genetic organization of these regions is conserved.

Amino Acid Sequence↗
PubMed1990

Nucleotide sequence analysis of a 10.5 kbp HindIII fragment of fowlpox virus: relatedness to the central portion of the vaccinia virus HindIII D region.

The nucleotide sequence of a 10465 bp HindIII genomic fragment from fowlpox virus (FPV) is presented. Analysis of the nucleotide sequence revealed 10 potential major open reading frames (ORFs). Five of these ORFs are predicted to encode polypeptides with significant homology to hypothetical polypeptides derived from nucleotide sequence analysis of the vaccinia virus (VV) HindIII D region. Interestingly, these homologous ORFs do not occur in the same tandem arrangement in the FPV genome as they do in the VV genome. These results are discussed.

Amino Acid Sequence↗
PubMed1989

Microtia reconstruction: does the cartilage framework grow?

The use of free rib cartilage ear frameworks in unilateral microtia reconstruction has prompted much discussion about their potential for growth. The senior author has reconstructed ear frameworks in 132 microtia patients, most of whom were under 3 years of age when surgery was initiated. Of this group, 29 were assessed for ear growth through comparison of the lead-plate model of the original normal ear to the normal ear growth and the reconstructed ear framework after a period of at least 2 years. Similarly, 14 reconstructed ears were compared to 14 normal ears at least 2 years after reconstruction. The perimeters of tracings made from the original lead plates and of tracings of normal and reconstructed ears were determined by image analysis techniques. The results demonstrated no significant difference in growth between normal ears and reconstructed ear frameworks after an interval of at least 2.5 years. Therefore, the reconstructed ear is growing at a rate similar to that of the normal ear.

Cartilage↗
PubMed1988

A histological evaluation of a functional endosseous, porous-surfaced, titanium alloy dental implant system in the dog.

We have previously reported the clinical and radiographic findings of a trial in dogs of a new dental implant system after a functional period of eight months. The present report consists of the corresponding qualitative and quantitative histological data. The implant system was fabricated from Ti-6A1-4V and employed a porous-surfaced configuration to achieve implant fixation by bone ingrowth. A similar porous surface was used on the apical 1/3 of the transgingival collar in an attempt to gain ingrowth and attachment of gingival connective tissue. The qualitative histological data confirmed that while such attachment to the collar did occur for some implants, in the majority of implants (22 of 32) the porous region of the collar became contaminated with bacterial plaque, resulting in implant failure (four implants) or suggesting future implant failure (18 implants). Statistical analyses of the quantitative histological data indicated that there were no significant differences in surface contact of bone with the middle third of the porous implant surface (CLF) when initial healing interval (four or eight weeks), implant location, or aspect of implant (buccal vs. lingual vs. mesial vs. distal) were compared. However, comparison of the current group of functional implants with an earlier group of similarly implanted non-functional implants indicated that function produced a highly significant increase in CLF.

Alloys↗
PubMed1986

A histological assessment of the initial healing response adjacent to porous-surfaced, titanium alloy dental implants in dogs.

We report here the results of a histological assessment of the initial healing response following implantation into the dog mandible of a porous-surfaced, titanium alloy endosseous dental implant. Two implants were placed in edentulous areas on each side of the mandible of each dog and covered with a full-thickness mucoperiosteal flap. The implant sites on one side of the mandible were allowed to head for four weeks, while those on the other side were allowed to head for eight weeks before the animals were killed. Histological specimens were obtained and assessed both qualitatively and by computer-assisted morphometry. All but one of the 24 implants were well-tolerated and healed with a variable ingrowth of bone into the porous-surface geometry. The histomorphometric measurements revealed that bone ingrowth had reached a plateau by four weeks of initial healing.

Alloys↗
PubMed1984

Reconstitution of a hormone-sensitive adenylate cyclase system. The pure beta-adrenergic receptor and guanine nucleotide regulatory protein confer hormone responsiveness on the resolved catalytic unit.

A hormone responsive adenylate cyclase has been reconstituted in phosphatidylcholine vesicles from its isolated protein components. The proteins used were the affinity chromatography purified (500-2000-fold) or pure Mr = 64,000 beta-adrenergic receptors (beta AR) isolated from hamster and guinea pig lung membranes, the pure heterotrimeric (Mr: alpha = 42,000; beta = 35,000; gamma approximately equal to 5,000) guanine nucleotide regulatory protein (Ns) isolated from human erythrocyte membranes; and the catalytic unit of the adenylate cyclase (C) solubilized from bovine brain caudate nucleus and resolved from beta AR and Ns by gel filtration. Adenylate cyclase activity in vesicles containing C alone was stimulated by forskolin but not by guanine nucleotides or by the beta-adrenergic agonist isoproterenol. Reconstitution of Ns and C interactions in the lipid vesicles resulted in guanine nucleotide but not beta-adrenergic agonist sensitivity. When beta AR was inserted together with Ns and C into lipid vesicles, the catalytic unit became responsive to beta-adrenergic agonists as well and this stimulation was blocked in a stereoselective manner by the beta-adrenergic antagonist alprenolol. Regulation of adenylate cyclase activity in the reconstituted system by beta-adrenergic agonists, guanine nucleotides, and Mg2+ showed properties similar to those observed in native membranes. The interactions of the various protein components in the reconstituted system were also monitored by GTPase activity. Such activity was observed to occur primarily as a result of receptor-Ns interactions. The results described in this report document the feasibility of studying hormone-responsive adenylate cyclase in a totally reconstituted system which retains the major regulatory properties of the enzyme in its native membrane-bound environment.

Adenylyl Cyclases↗