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Biomedical subjects

J Woodward

Publications and source records attributed to J Woodward.

At least 19 recordsLinked to original sources
PubMed2000

Activation of mitogen-activated protein kinases is required for alpha1-adrenergic agonist-induced cell scattering in transfected HepG2 cells.

Activation of alpha1B-adrenergic receptors ((alpha1B)AR) by phenylephrine (PE) induces scattering of HepG2 cells stably transfected with the (alpha1B)AR (TFG2 cells). Scattering was also observed after stimulation of TFG2 cells with phorbol myristate acetate (PMA) but not with hepatocyte growth factor/scatter factor, epidermal growth factor, or insulin. PMA but not phenylephrine rapidly activated PKCalpha in TFG2 cells, and the highly selective PKC inhibitor bisindolylmaleimide (GFX) completely abolished PMA-induced but not PE-induced scattering. PE rapidly activated p44/42 mitogen-activated protein kinase (MAPK), p38 MAPK, c-Jun N-terminal kinase (JNK), and AP1 (c-fos/c-jun). Selective blockade of p42/44 MAPK activity by PD98059 or by transfection of a MEK1 dominant negative adenovirus significantly inhibited the PE-induced scattering of TFG2 cells. Selective inhibition of p38 MAPK by SB203850 or SB202190 also blocked PE-induced scattering, whereas treatment of TFG2 cells with the PI3 kinase inhibitors LY294002 or wortmannin did not inhibit PE-induced scattering. Blocking JNK activation with a dominant negative mutant of JNK or blocking AP1 activation with a dominant negative mutant of c-jun (TAM67) significantly inhibited PE-induced cell scattering. These data indicate that PE-induced scattering of TFG2 cells is mediated by complex mechanisms, including activation of p42/44 MAPK, p38 MAPK, and JNK. Cell spreading has been reported to play important roles in wound repair, tumor invasion, and metastasis. Therefore, catecholamines acting via the (alpha1)AR may modulate these physiological and pathological processes.

Adrenergic alpha-Agonists↗
PubMed2000

First-principles determination of hybrid bilayer membrane structure by phase-sensitive neutron reflectometry.

The application of a new, phase-sensitive neutron reflectometry method to reveal the compositional depth profiles of biomimetic membranes is reported. Determination of the complex reflection amplitude allows the related scattering length density (SLD) profile to be obtained by a first-principles inversion without the need for fitting or adjustable parameters. The SLD profile so obtained is unique for most membranes and can therefore be directly compared with the SLD profile corresponding to the chemical compositional profile of the film, as predicted, for example, by a molecular dynamics simulation. Knowledge of the real part of the reflection amplitude, in addition to enabling the inversion, makes it possible to assign a spatial resolution to the profile for a given range of wavevector transfer over which the reflectivity data are collected. Furthermore, the imaginary part of the reflection amplitude can be used as a sensitive diagnostic tool for recognizing the existence of certain in-plane inhomogeneities in the sample. Measurements demonstrating the practical realization of this phase-sensitive technique were performed on a hybrid bilayer membrane (self-assembled monolayer of thiahexa (ethylene oxide) alkane on gold and a phospholipid layer) in intimate contact with an aqueous reservoir. Analysis of the experimental results shows that accurate compositional depth profiles can now be obtained with a spatial resolution in the subnanometer range, primarily limited by the background originating from the reservoir and the roughness of the film's supporting substrate.

Biophysics↗
PubMed2000

The mechanism of cellulase action on cotton fibers: evidence from atomic force microscopy.

Two cellulases from Trichoderma reesei--an exoglucanase, CBH I, and an endoglucanase, EG II--alone and in combination were incubated with cotton fibers. The effects of the cellulases on the surfaces of the cotton fibers were examined by atomic force microscopy. At high magnification, the physical effects on the fibers caused by the two types of enzymes were considerably different. Treatment with CBH I resulted in the appearance of distinct pathways or tracks along the length of the macrofibril. Treatment with EG II appeared to cause peeling and smoothing of the fiber surface. In combination, their effect was observed to be greatest when both enzymes were present simultaneously. When fibers smoothed by treatment with EG II were treated subsequently with CBH I, further evidence of path way formation caused by the action of CBH I along the fibers was observed. Incubation with a cellulase from Thermotoga maritima that lacks a cellulose binding domain had no effect on the surface of cotton fibers. These images provide the first physical evidence of differences in the effect of cellulase components action on the surface of cotton fibers and provide evidence for the movement or tracking of CBH I along the fibers. The first AFM image of CBH I molecules are presented.

Cellulase↗
PubMed2000

In vivo chondroprotection and metabolic synergy of glucosamine and chondroitin sulfate.

Supplements of glucosamine hydrochloride, low molecular weight chondroitin sulfate, and manganese ascorbate were tested separately and in combination for their ability to retard progression of cartilage degeneration in a rabbit instability model of osteoarthrosis. Computerized quantitative histologic evaluation of safranin O stained sections of the medial femoral condyles measured the grade and extent of tissue involvement of lesions. Severe lesions (Mankin grade greater than 7) were absent in all animals supplemented with a dietary mixture of glucosamine, chondroitin sulfate, and manganese ascorbate. Total linear involvement (mm of lesioned surface) and total grade (mean grade x number of lesions per animal) were reduced significantly in animals given the combination compared with controls (59% and 74% respectively). Animals supplemented with glucosamine, chondroitin sulfate, or manganese ascorbate alone had less moderate and severe tissue involvement than controls but not to the extent of the combined group. In vitro, a combination of glucosamine hydrochloride and chondroitin sulfate acted synergistically in stimulating glycosaminoglycan synthesis (96.6%). Chondroitin sulfate and manganese ascorbate but not glucosamine were effective in inhibiting degradative enzyme activity. These data suggest that the disease modifying effect (the ability to retard progression of cartilage degeneration) of a mixture of glucosamine, chondroitin sulfate, and manganese ascorbate is more efficacious than either agent alone.

Animals↗
PubMed1999

Glucose and lactate metabolism after severe human head injury: influence of excitatory neurotransmitters and injury type.

The survival of traumatized brain tissue depends on energy substrate delivery and consumption. Excitatory amino acids produce a disturbance of ion homeostasis and thus, increase energy demand. In head-injured patients, massive release of glutamate has been reported, especially in patients with focal contusions. Therefore, we studied the interrelationship between glutamate, glucose and lactate in relation to the type of injury. We investigated 37 severely head-injured patients in which a microdialysis probe was placed next to a focal contusion (n = 14) or together with a ventricular catheter in diffusely injured tissue (n = 23). Within-subject Spearman-rank correlation revealed an overall strong relationship between glutamate and lactate (p < 0.001) and glutamate and glucose (p < 0.01), but not between glucose and lactate (n.s.). The interrelationship was more pronounced in diffusely injured brain (normal CT appearance) compared to the contused tissue. The results demonstrate that glutamate clearly influences the release of lactate following injury, supporting the hypothesis that glutamate "drives" glycolysis in astrocytes. The strong positive correlation between glutamate and glucose might indicate an effect of glutamate upon glucose uptake by cells which differs according to the type of injury.

Adult↗
PubMed1999

Evidence for time-dependent glutamate-mediated glycolysis in head-injured patients: a microdialysis study.

In the brain, lactate is not only a marker of anaerobic glycolysis due to hypoxia/ischemia, but also a neuronal energy source which is provided by glutamate-induced astrocytic glycolysis. In the present study we wanted to investigate the relationship between glutamate release and lactate production during the entire time-course and during three time periods of microdialytic monitoring in 54 severely head injured patients. Within-subject Spearman rank correlations were calculated in each period for glutamate and lactate, for each patient and the mean of all correlation coefficients were analyzed for difference from zero by a one-sample t-test. The results show a strong overall positive relationship between glutamate and lactate. However, during the first 12 hours after injury, there was no significant correlation. Thereafter, good correlation was seen. The splitting of patients into groups with good (Glasgow Outcome Scale; GOS 0-2) and poor outcome (GOS 3-4) showed a similar strong correlation for patients with good outcome, but this was lost for patients with poor outcome. The results clearly indicate that glutamate "drives" astrocytic lactate production in head-injured patients. The contribution of glutamate to overall lactate release is thus time-dependent. During the first 12 hours after injury, factors such as hypoxia, ischemia or edema overshadowed glutamate-induced glycolysis in astrocytes. In addition, the effect of glutamate is more pronounced in patients with good outcome.

Adult↗
PubMed1998

Cortical extracellular sodium transients after human head injury: an indicator of secondary brain damage?

Animal studies indicate that elevated extracellular sodium can increase glutamate-induced excitotoxicity. Therefore, we investigated the relationship between sodium and glutamate and the effect of changes in sodium concentrations on the outcome of head-injured patients. Thirty-four (34) patients were selected for this study and divided into a group of patients having episodes (> or = 30-min) of high sodium in dialysates (> or = 200 mM; HIGH, n = 11) and a group of patients having no such episodes (NORMAL, n = 23). Levels for sodium (226 +/- 5.7 mM), glutamate (12.53 +/- 2.2 microM) and ICP (32.2 +/- 4.0 mm Hg,) were relatively high during the high sodium episodes. Overall, mean values for glutamate, ICP and outcome did not differ amono both groups. The mean dialysate sodium concentration, however, was significantly higher in the HIGH (178 +/- 6 mM) compared to the NORMAL group (158 +/- 3 mM; p < 0.01). Spearman rank correlation between sodium and glutamate or ICP were not significant. The HIGH sodium group did not have significantly more patients with poor outcome than the NORMAL group. The results indicated sodium concentrations did not affect the outcome of head-injured patients. However, other sodium monitoring techniques are desirable to elucidate these apparent potentially major sodium transients, which we have observed in the human cortex, after severe head injury.

Adult↗
PubMed1998

In vitro activity of RPR 106972 alone and in combination with vancomycin, ampicillin, and gentamicin against multidrug-resistant enterococci.

This investigation used checkerboard and time-kill assays to evaluate the in vitro activity of RPR 106972 (45% pristinamycin IB and 55% pristinamycin IIB) alone and in combination with vancomycin or ampicillin +/- gentamicin against multidrug-resistant enterococci. The checkerboard procedure resulted in synergistic or additive effects in 91% of the isolates with the combination of RPR 106972 plus vancomycin versus 68% with RPR 106972 plus ampicillin. The addition of gentamicin to either combination resulted in synergistic or additive results in 100% of the isolates. Inhibitory activity was observed with the time-kill assay with mean change in log10 CFU/mL at 24 h of -0.31 for RPR 106972, 3.3 for vancomycin, -0.46 for RPR 106972 plus vancomycin, and -0.35 for RPR 106972 plus vancomycin and gentamicin. No antagonism was noted with any of the combinations. RPR 106972 demonstrates good inhibitory activity against Enterococcus faecium and may prove useful in the treatment of enterococcal infections.

Ampicillin↗
PubMed1998

Enzymatic conversion of sucrose to hydrogen

The enzymatic conversion of sugars to hydrogen could be a promising method for alternative fuel production. Maple tree sap is a source of environmental sugar (e.g., sucrose) that has the potential to be converted into hydrogen using the enzymes invertase, glucose dehydrogenase (GDH), hydrogenase, and glucose isomerase (GI) and the cofactor NADP+/NADPH. The kinetics of hydrogen production have been studied, and optimal conditions for hydrogen production are described. At low initial sucrose concentrations, in the absence of glucose isomerase, stoichiometric yields of 1 mol of H2/mol of sucrose were achieved. At higher sucrose concentrations, the yield of hydrogen declined so that at an initial sucrose concentration of 292 mM only 7% yield of hydrogen was obtained. The reason for this low yield was studied and shown not to be caused by enzyme inactivation or a pH drop during the reaction but due to an instability of the cofactor NADP+. Although gluconic acid inhibited both NADPH production and oxidation by GDH and hydrogenase, respectively, it was not the major cause of NADP+ instability. Fructose was also shown to be converted to hydrogen if GI was present in the reaction mixture. Also, by starting with sucrose, 1. 34 mol of H2/mol of sucrose was obtained if GI was present in the reaction mixture.

Journal Article↗
PubMed1997

Performance of anesthesia machines' devices that are not part of the Food and Drug Administration's daily checkout.

OBJECTIVE: The Food and Drug Administration's (FDA) checkout recommendations are to be applied, at least daily, on anesthesia machines. Devices included in the checkout are crucial to the safe operation of the machine. Remaining devices do not need to be checked as often. However, they should be checked at some appropriate interval. We calculated the reliability of the non-FDA checkout devices, to predict failure rates of these devices. METHODS: The study included 36 North American Drager Narkomed anesthesia machines that were in service a total of 109,410 days at a university hospital. Reliability (i.e., statistical) analyses were done using in-house data recorded by biomedical technicians during 3359 monthly machine inspections. If any one device was operating outside of the limits of the manufacturer's specifications, the machine was labeled as having failed its inspection. RESULTS: Assumptions of the failure analysis were satisfied. The mean time between failures equaled 1351 days or 3.7 years (lower 95% confidence bound 1123 days or 3.1 years). The mean daily probability of one or more devices failing to perform within the manufacturer's specification between inspections equaled 1.1, 2.2%, and 4.4% for inspections every 1, 2, or 4 months, respectively. Probabilities that a machine would fail on demand between inspections were approximately equal to the mean daily probabilities of machine failure. The mean number of days per year that a machine would be operating with a device that is outside of the limits of its specifications equaled 4, 8, and 12, days, respectively. The mean daily probabilities of failure and the probabilities of failure on demand were both directly proportional to the inspection interval. CONCLUSIONS: Our failure analysis provides a rational basis for choosing an appropriate inspection interval for anesthesia machines' devices that are not included in the FDA's checkout recommendations.

Anesthesiology↗
PubMed1997

The significance of white-centered retinal hemorrhages in the shaken baby syndrome.

Retinal hemorrhages in healthy children with or without a history of associated trauma are a strong indicator of child abuse. This report describes six cases of battered infants who presented with white-centered retinal hemorrhages. We discuss potential mechanisms for the presence of white-centered retinal hemorrhages in battered children.

Battered Child Syndrome↗
PubMed1997

Anaerobic degradation of polycyclic aromatic hydrocarbons and alkanes in petroleum-contaminated marine harbor sediments.

Although polycyclic aromatic hydrocarbons (PAHs) have usually been found to persist under strict anaerobic conditions, in a previous study an unusual site was found in San Diego Bay in which two PAHs, naphthalene and phenanthrene, were oxidized to carbon dioxide under sulfate-reducing conditions. Further investigations with these sediments revealed that methylnaphthalene, fluorene, and fluoranthene were also anaerobically oxidized to carbon dioxide in these sediments, while pyrene and benzo[a]pyrene were not. Studies with naphthalene indicated that PAH oxidation was sulfate dependent. Incubating the sediments with additional naphthalene for 1 month resulted in a significant increase in the oxidation of [14C]naphthalene. In sediments from a less heavily contaminated site in San diego Bay where PAHs were not readily degraded, naphthalene degradation could be stimulated through inoculation with active PAH-degrading sediments from the most heavily contaminated site. Sediments from the less heavily contaminated site that had been adapted for rapid anaerobic degradation of high concentrations of benzene did not oxidize naphthalene, suggesting that the benzene- and naphthalene-degrading populations were different. When fuels containing complex mixtures of alkanes were added to sediments from the two sites, there was significant degradation in the alkanes. [14C]hexadecane was also anaerobically oxidized to 14CO2 in these sediments. Molybdate, a specific inhibitor of sulfate reduction, inhibited hexadecane oxidation. These results demonstrate that a wide variety of hydrocarbon contaminants can be degraded under sulfate-reducing conditions in hydrocarbon-contaminated sediments, and they suggest that it may be possible to use sulfate reduction rather than aerobic respiration as a treatment strategy for hydrocarbon-contaminated dredged sediments.

Alkanes↗
PubMed1996

Glutamate release and cerebral blood flow after severe human head injury.

Elevations of extracellular glutamate have been found in patients with prolonged brain ischemia and focal cerebral contusions, following severe head injury. About 30% of severely head injured patients develop cerebral ischemia, defined as CBF < 18 ml/100g/min. Patients with both global and regional cerebral ischemia have the worst outcome. However, the relationship between CBF and EAA release is not well understood in head injured humans, and may differ from the findings in normal animals. To study the relationship between EAA release and CBF after severe head injury, we performed cerebral blood flow measurements using stable xenon enhanced computed tomography and correlated these with glutamate release in the extracellular fluid, measured by continuous microdialysis, in 25 severely head injured patients. Sustained cerebral blood flow reductions below the threshold for ischemic neuronal damage was closely related to massive excitatory amino acid release, as in previous animal studies. In patients without secondary ischemia, or focal contusions, delayed post-traumatic glutamate release appeared to be only transient or did not occur at all.

Cerebrovascular Circulation↗
PubMed1996

Dose-response relation between terfenadine (Seldane) and the QTc interval on the scalar electrocardiogram: distinguishing a drug effect from spontaneous variability.

The primary goal of this investigation was to describe the effect of terfenadine on the QT interval corrected for heart rate (QTc) of the scalar electrocardiogram (ECG). The design was double-blind, four-period crossover, dose escalation, which involved 28 normal healthy volunteers and 28 patients with stable cardiovascular disease. At baseline, the normal subjects had a mean QTc interval of 407 msec, whereas the patients with cardiovascular disease had a mean QTc interval of 417 msec (p<0.01). The largest increase in mean QTc on terfenadine was 24 msec in a normal subject and 28 msec in a patient with cardiovascular disease. The longest average QTc observed was 449 msec and 501 msec in any normal subject and patient with cardiovascular disease, respectively. Compared to baseline, terfenadine 60 mg twice daily is associated with a QTc increase of 6 msec in normal subjects and a 12 msec increase in patients with cardiovascular disease (p<0.01 vs baseline; p>0.05 when the two populations were compared). Although the QTc increase from baseline are statistically significant, the magnitude of the spontaneous variability in QTc in the same patients is much greater. Because 40 ECGs were obtained while taking placebo in each participant, the spontaneous variability in QTc interval with placebo was also described. Only one of the 28 normal subjects had a mean baseline QTc=440 msec, yet 14 of the 28 normal subjects had at lease one of the 40 placebo ECGs with a QTc=440 msec. The 28 patients with cardiovascular disease had a mean QTc at baseline of 417 msec; yet 20 of 28 had at lease one ECG on placebo with a QTc interval = 440 msec. On the average, the QTc fluctuated 56 msec in each patient during placebo administration. From the observed placebo variability, we calculated that an increase in QTc of=35 msec while receiving drug therapy is likely to represent a drug effect at the 95% confidence interval.

Aged↗
PubMed1996

Comparison of the properties of native and pentaammineruthenium(III)-modified xylanase.

Two xylanases, xynA of Bacillus pumilus and xyn II of Trichoderma reesei, were purified and then modified by the attachment of pentaammineruthenium, thereby resulting in the generation of a xylanase with veratryl alcohol oxidase activity. Hydrolytic activity of T. reesei xyn II on soluble xylans was unchanged by modification with pentaammineruthenium; however, modification of B. pumilus xynA greatly reduced xylan hydrolysis unless the active site of the xylanase was protected with xylose during the modification. The presence of histidine, cysteine, or reduced glutathione during xylan hydrolysis greatly increased the xylanase activity of the pentaammineruthenium-modified B. pumilus xylanase. Glycine, glutamic acid, methionine, or oxidized glutathione had no effect on xylanase activity.

Alcohol Oxidoreductases↗