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Biomedical subjects

J Taylor

Publications and source records attributed to J Taylor.

At least 379 records · Page 21Linked to original sources
PubMed1993

Pyruvate and lactate metabolism in the in vivo dog heart.

Pyruvate increases the phosphorylation potential in perfused heart to a greater extent than the closely correlated substrate L-lactate. Therefore, metabolism of these compounds was studied in the myocardium of intact dogs. Phosphocreatine/ATP was increased 23% at 5.3 mM plasma pyruvate but was not significantly increased by lactate except at the highest concentration (17.5 mM in blood). Calculated [ADP] fell during pyruvate infusion from 51.5 +/- 2.0 to 38.6 +/- 3.3 microM but did not change significantly during lactate infusion. Intracellular free [Mg2+] fell from 705 +/- 53 to 498 +/- 30 microM at the highest pyruvate infusion and from 692 +/- 112 to 417 +/- 19 microM with lactate infusion. Extraction of both substrates was linear at low concentrations, reaching 0.56 mumol lactate.min-1.g wet wt-1 at 17.5 mM blood lactate and 0.58 mumol pyruvate.min-1.g wet wt-1 at 5.3 mM plasma pyruvate. Therefore, lactate uptake was almost five times lower than pyruvate uptake at similar concentrations. Elevated pyruvate (> 3 mM) resulted in almost complete inhibition of net lactate uptake. Infused [3-13C]lactate or -pyruvate gave rise to labeled glutamate and alanine in vivo, but labeled lactate was not visible when [3-13C]pyruvate was the substrate. The 13C enrichment of myocardial lactate was similar to alanine and acetyl CoA with infused [3-13C]lactate but was only one-half that of alanine and acetyl CoA when [3-13C]-pyruvate was the substrate, indicating a possible inhibition of lactate dehydrogenase.

Animals↗
PubMed1993

Migration of bovine bronchial epithelial cells to extracellular matrix components.

Migration of epithelial cells is an important feature of wound healing. Components of extracellular matrix stimulate migration of other cells, and we hypothesized that basement membrane components, laminin and type IV collagen, stimulate migration of bovine bronchial epithelial cells (BBEC). BBEC cultured for 3 days were used in migration assays using the blindwell chamber technique. BBEC migrated in a concentration-dependent manner to laminin, type IV collagen, and fibronectin. "Checkerboard" analysis demonstrated that the migration was directional for each of the components studied. We also evaluated the stimulatory activity of fibronectin fragments. A fragment containing the RGDS peptide was stimulatory of migration while other fragments were much less so, suggesting a role for RGDS-sensitive, integrin-mediated mechanisms. In order to evaluate whether bound or soluble matrix components were required to direct cell migration, we performed haptotaxis assays with precoated filters in the migration chambers. Fibronectin-precoated filters demonstrated significant stimulation of migration, suggesting that some of the migration in our original assays with fibronectin present in the lower chambers could be termed haptotactic. laminin- and type IV collagen-precoated filters were less active. When insulin was used as a chemoattractant, the fibronectin-precoated filters were more facilitatory of migration than the other matrix coatings. In summary, BBEC can chemotactically migrate to extracellular matrix components. Thus, the composition of the provisional matrix that forms at sites of epithelial injury may play an important role in the repair processes that occur after injury to the bronchial epithelium.

Amino Acid Sequence↗
PubMed1993

Development of aphasia, apraxia, and agnosia and decline in Alzheimer's disease.

OBJECTIVE: The purpose of this study was to compare the stage and the subtype models of disease progression in Alzheimer's disease. The authors address the issue of whether the overall rate of clinical decline is different in Alzheimer's disease patients with and without early development of aphasia, apraxia, or agnosia. METHOD: The study was a case series study. Two separate cohorts of Alzheimer's disease patients were used, one from an ongoing single center study at Stanford University (N = 57) and the other from a multicenter project across the state of California (N = 70). Patients were assessed every 6 months in the Stanford study and yearly in the state study. All patients were assessed at least three times. The outcome measure was the average rate of decline on the Mini-Mental State examination. RESULTS: The average rates of decline on the Mini-Mental State were computed for each subject. Subjects were then divided among groups according to whether and when they exhibited aphasia, agnosia, or apraxia. The effects of the presence of aphasia, agnosia, or apraxia were assessed by comparing the average rates of decline on the Mini-Mental State. CONCLUSIONS: Alzheimer's disease patients who developed aphasia or apraxia declined more rapidly than those patients who did not develop either sign. These results were not attributable to differences in Mini-Mental State scores at entry into the study. The results suggest the presence of subtypes of Alzheimer's disease in which accelerated decline is associated with the early appearance of certain neurological signs.

Age Factors↗
PubMed1993

The lateral atlanto-axial joints and their synovial folds: an in vitro study of soft tissue injuries and fractures.

Thirty victims of blunt cervical trauma, who did not survive (acute death group), were studied at autopsy as were 11 patients who survived trauma for more than 1 month and ten controls without any known cervical trauma. All specimens were sagitally sectioned in 2-mm slices and carefully examined for injuries to the lateral parts of the atlanto-axial joints. In the acute death group, five cases showed a rupture of the joint capsule, three of these with a massive hemarthrosis. In 17 cases there was bruising around the second cervical spinal nerve. Bruising of the intra-articular synovial fold was present in 15 cases, the posterior synovial fold being most commonly affected. There were five intra-articular fractures of the lateral masses, in three cases combined with a dens fracture. In two cases a bone fragment from the fracture compressed and obliterated the lumen of the vertebral artery. The findings are discussed in relation to pain after cervical trauma.

Adolescent↗
PubMed1993

The time-course of alcohol impairment of general aviation pilot performance in a Frasca 141 simulator.

This study examined the time-course of alcohol impairment of general aviation pilot simulator performance. We tested 14 young (mean age 25.8 years) and 14 older (mean age 37.9 years) pilots in a Frasca 141 simulator during alcohol and placebo conditions. In the alcohol condition, pilots drank alcohol and were tested after reaching 0.10% BAL, and then 2, 4, 8, 24, and 48 h after they had stopped drinking. They were tested at the same times in the placebo condition. Alcohol impaired overall performance. Alcohol impairment also depended on the order in which subjects participated in the alcohol and placebo sessions, with larger decrements for the alcohol-placebo order than for the opposite order. To examine the influence of alcohol independent of session order effects, we compared performance in the first alcohol session with performance in the first placebo session. This analysis showed that alcohol significantly reduced mean performance in the alcohol condition at 0.10% BAL and at 2 h. In addition, alcohol increased variability in performance in the alcohol session from 0.10% BAL to 8 h, suggesting that some subjects were more susceptible to alcohol than others. Older pilots tended to perform some radio communication tasks less accurately than younger pilots.

Adult↗
PubMed1992

Immunisation with canarypox virus expressing rabies glycoprotein.

Poxviruses have many useful features as vectors for genes that carry immunising antigens from other viruses, such as ease of production and induction of cellular and humoral immunity, but there is concern about the safety of vaccinia virus. We turned to an avian poxvirus (canarypox); this virus undergoes abortive replication in mammalian cells that enables presentation of early gene products to the immune system. Canarypox virus was used as a vector for the rabies glycoprotein G gene. The safety and efficacy of the recombinant (ALVAC-RG; vCP65) were tested in several animal species, then it was subjected to a phase 1 clinical trial. Twenty-five volunteers were randomly assigned to subcutaneous injections of the recombinant (three groups [A, B, and C] received two doses each of 10(3.5), 10(4.5), and 10(5.5) tissue-culture infectious doses50, respectively) or of human diploid cell culture vaccine (HDC; 6.52 international potency units per dose). 28 days after the second dose, all nine ALVAC-RG group-C subjects and two of three group-B subjects had rabies neutralising antibody concentrations of at least 0.5 IU/ml, the level associated with protection in animals. Although the geometric mean titre of these antibodies at that time was lower in group C than in the ten HDC recipients (4.4 [range 0.9-12.5] vs 11.5 [4.7-25.3] IU/ml), a single booster dose at 6 months induced a recall response in volunteers primed with either vaccine. Side-effects associated with ALVAC-RG were mild and of short duration and occurred at similar frequency to those of HDC vaccine. This study has shown the potential of non-replicating poxviruses as vectors for vaccination in human beings. Trials of canarypox-virus recombinants at higher doses and by other routes of administration are needed.

Adult↗
PubMed1992

Evidence for regulatory genes on mouse chromosome 7 that affect the quantitative expression of proteins in the fetal and newborn liver.

A series of deletions around the albino locus on mouse chromosome 7 is believed to include one or more regulatory genes that control the activities of a cluster of liver enzymes. To further characterize the functions of this region of the mouse genome, we have used quantitative two-dimensional electrophoresis to analyze the effects of two of these deletions, c3H and c14CoS, on the expression of liver proteins. More than 400 distinct protein gene products were quantitated in livers from fetal and newborn wild-type homozygous (cch/cch), heterozygous (cch/c3H or cch/c14CoS), and deletion homozygous (c3H/c3H or c14CoS/c14CoS) mice. Livers of fetal and newborn c3H heterozygotes and homozygous wild-type littermates produced qualitatively identical protein patterns after two-dimensional electrophoresis. In livers of c3H homozygous fetuses, however, abnormal amounts (either increased or decreased relative to homozygous wild-type and heterozygous littermates) of 29 proteins were found. Twenty-eight of these 29 protein anomalies were also found in livers of newborn c3H homozygotes. Livers of fetal and newborn mice homozygous for the c14CoS deletion, which overlaps the c3H deletion and produces a similar phenotype, expressed normal amounts of these proteins. One of the 29 proteins (MSN807) has an amino-terminal sequence similar to a 23-kDa translationally controlled protein abundant in mouse erythroleukemia and sarcoma-180 cells. These results suggest that normal chromosome 7 contains genes, located within the region of the c3H but not the c14CoS deletion, that regulate the abundance of specific proteins in the liver. These proteins cannot be related to the phenotypic alterations shared by the c3H and c14CoS deletions.

Albinism↗
PubMed1992

Mouse liver protein database: a catalog of proteins detected by two-dimensional gel electrophoresis.

Alterations in the abundance or structure of mouse liver proteins are being studied using two-dimensional gel electrophoresis (2-DE) to build a database of protein changes correlating with exposure to ionizing radiation or toxic chemicals. Thus far, studies have included the analysis of proteins from the offspring of exposed parents or from the exposed individuals themselves. In order to characterize and identify proteins found altered by such exposures, sex- and strain-related differences in protein patterns have been analyzed, and the subcellular locations of a large portion of the mapped proteins have been determined. As part of these studies, data are collected and stored using a variety of computer hardware and software tools that allow the accumulation of information on the origin of samples, gel identification, experiment description, and protein similarities and differences. This accumulation of information constitutes the mouse liver protein database. Relational database software is used to tie the different facets of the database together so that the results of a variety of experiments can be compared and interrelated. The database optimizes the information obtained from 2-DE gel sets by allowing use of the data for many purposes, including monitoring of gel resolution to ensure the collection of high quality data and correlation of protein effects induced by different agents. This first edition of the Argonne National Laboratory mouse liver protein database lays the foundation for future work and communication that should elucidate the significance of observed protein effects as possible markers of exposure to toxic agents.

Animals↗
PubMed1992

Use of principal components analysis for mutation detection with two-dimensional electrophoresis protein separations.

The application of two-dimensional electrophoresis (2-DE) to mutation detection requires the capability to monitor each protein in a 2-DE pattern for significant changes in abundance indicative of a mutation event. Previously, mutation searches were done using a univariate outlier detection method in which each protein spot was considered independently in a classical outlier search. An alternative approach to analysis of 2-DE patterns for quantitative changes is a multivariate procedure which takes advantage of the observation that protein spots in a 2-DE pattern often represent correlated rather than independent measurements. We have compared the efficiency of univariate and multivariate procedures for mutation detection using data from the Argonne National Laboratory 2-DE database of mouse liver proteins. Analyses involving a total of over 1500 gels were performed to compare the performance of a multivariate method based on principal components analysis (PCA) with the univariate method. Up to 279 spots from each pattern were used for PCA. First, a simulation was performed to assess the detection efficiency of PCA for single protein spots decreased in abundance by 50%. Then, the ability to detect actual mutations was tested using eight confirmed mutations. Results show that, compared to a univariate approach to analysis of data from the mouse model system, the multivariate method increases the number of protein spots on each 2-DE pattern that can be monitored for quantitative changes indicative of mutations by compensating for variables that contribute to the background quantitative variability of protein spots.

Animals↗