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Biomedical subjects

S J Taylor

Publications and source records attributed to S J Taylor.

At least 19 recordsLinked to original sources
PubMed2000

gamma-aminobutyric acid mimetic drugs differentially inhibit the dopaminergic response to cocaine.

Dopaminergic activity in the mesocorticolimbic system is associated with reinforcing properties of psychostimulant drugs. We previously demonstrated that increased gamma-aminobutyric acid (GABA)-ergic activity produced by gamma-vinyl GABA [D,L-4-amino-hex-5-enoic acid (Vigabatrin(R))], an irreversible inhibitor of GABA-transaminase, attenuated cocaine, nicotine, heroin, alcohol, and methamphetamine-induced increases in extracellular nucleus accumbens dopamine as well as behaviors associated with these biochemical changes. In the present study, using in vivo microdialysis techniques, we compared three different strategies to increase GABAergic activity in order to modulate cocaine-induced increase in extracellular dopamine. Our data demonstrate that the anticonvulsant 1-(2-(((diphenylmethylene)amino)oxy)ethyl)-1,2,5, 6-tetrahydro-3-pyridinecarboxylic acid hydrochloride (NNC-711), a GABA uptake inhibitor, dose and time dependently diminished increases in extracellular dopamine following acute cocaine challenge. Furthermore, we demonstrated that cyclized analogue of vigabatrin, a competitive reversible GABA-transaminase inhibitor, is a more potent inhibitor of cocaine-induced dopamine increase than vigabatrin. Our data suggest that in addition to irreversible inhibition of GABA transaminase, inhibition of GABA uptake represent another potentially effective, indirect strategy for the treatment of cocaine abuse.

Animals↗
PubMed1999

Responsiveness of common outcome measures for patients with low back pain.

STUDY DESIGN: A prospective cohort study assessing the responsiveness of two disease-specific questionnaires and a generic health questionnaire for patients with low back pain and sciatica. OBJECTIVES: To compare the responsiveness of the eight scales and two summery scales of the SF-36 questionnaire with that of the Oswestry Disability Index and Low Back Outcome Score questionnaires. SUMMARY OF BACKGROUND DATA: Evaluation of treatment outcome is being determined more frequently from a patient's perspective, particularly the impact treatment has on current health status. METHODS: Patients were recruited from two orthopedic back pain clinics in a tertiary hospital. Patients completed the pretreatment questionnaire 1 month before treatment and follow-up questionnaires a minimum of 2-6 months after treatment. Patients undergoing surgery were also observed for a minimum of 2 years. RESULTS: Overall, the Oswestry Disability Index was most responsive; however, individual scales from the SF-36 questionnaire showed equal or greater sensitivity to change than the Oswestry Disability Index in each of the patient subgroups. The SF-36 Role Physical scale was prone to floor effects (a high percentage of respondents score zero), and the change scores from the SF-36 Role Emotional scale varied by 100 points in either direction in each of the patient subgroups. CONCLUSION: Responsiveness varied according to which method was used in its calculation. The responsiveness of the SF-36 questionnaire shows that it can be a useful adjunct in the assessment of patients with low back pain when combined with disease-specific questionnaires.

Disability Evaluation↗
PubMed1999

A tyrosine-phosphorylated protein that binds to an important regulatory region on the cool family of p21-activated kinase-binding proteins.

The p21-activated kinases (Pak) are major targets of the small GTPases Cdc42 and Rac. We, and others, recently identified a family of proteins termed Cool/Pix, which interact with Pak3. In cells, p50(Cool-1) suppresses Pak activation by upstream activators; p85(Cool-1) has a permissive effect on Pak activation, and we now show that the closely related Cool-2 stimulates Pak kinase activity. To understand the differential regulation of Pak by Cool proteins, we screened for Cool-interacting proteins by affinity purification and microsequencing. This has led to the identification of two closely related proteins called Cat (Cool-associated, tyrosine phosphorylated), which contain a zinc finger followed by three ankyrin repeats. Cat-1 is identical to the recently identified binding partner for the beta-adrenergic receptor kinase (betaARK or GRK-2), which was shown to have Arf-GAP activity. Cat-1 and Cat-2 both bind to the COOH-terminal region of p85(Cool-1) and p85(Cool-2) but do not bind to p50(Cool-1). Cat-1 is tyrosine-phosphorylated in growing NIH 3T3 fibroblasts, and its tyrosine phosphorylation is increased following cell spreading on fibronectin, decreased in cells arrested in mitosis, and increased in the ensuing G(1) phase. Cat proteins are tyrosine-phosphorylated when co-expressed in cells with the focal adhesion kinase Fak and Src. These findings suggest that in addition to playing a role in Cool/Pak interactions, Cat proteins may serve as points of convergence between G protein-coupled receptors, integrins, Arf GTPases, cell cycle regulators, and Cdc42/Rac/Pak signaling pathways.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Novel screening methods--the key to cloning commercially successful biocatalysts.

Providing sufficient biocatalyst to support the demands of multi tonne product supply can be problematical. Here we describe how screening for and cloning a gamma-lactamase overcame biocatalyst supply issues, and greatly improved the actual biocatalytic process. The isolation of an expressing gamma-lactamase clone from a gene library necessitated a combination of classical molecular biology techniques together with innovative screening methods to identify a functional clone. Once isolated the enzyme was characterised with regard to its process performance and proved to be active at 500 g L(-1) substrate. Further development of the recombinant fermentation and downstream processing has resulted in the ability to produce sufficient biocatalyst from one 5001 fermentation to resolve 5 metric tonnes of (+/-)-lactam, whilst simplifying the process chemistry greatly.

Amidohydrolases↗
PubMed1999

Effects of low-dose isoflurane on saccadic eye movement generation.

The effects of 0.15% quasi-steady-state end-tidal isoflurane on two saccadic eye-movement tests were examined in five volunteers using a newly devised computer-based recording system. The tests were saccadic latency and a countermanding task, the latter being an indicator of the highest levels of conscious performance. A moving light-emitting diode target was displayed on a screen and in the saccadic-latency task the latency of eye movement to the target was measured. In all five subjects the latency increased with anaesthetic by an amount which varied from 8 to 45 ms. This result was significantly different (p < 0.05) from subjects without anaesthetic. In the countermanding task, the subject had to voluntarily inhibit movement to the target. Again anaesthetic increased the latency of response, which varied from 6 to 33 ms. This result was significantly different (p < 0.05) from subjects without anaesthetic. In these studies it appeared that two tasks, one a simple latency test and the other, the countermanding task, requiring higher cortical processing were equally impaired at subanaesthetic concentrations of isoflurane.

Anesthetics, Inhalation↗
PubMed1999

An evaluation of prostaglandin E2 vaginal gel use in practice.

OBJECTIVE: The purpose of this study was to investigate the effectiveness of prostaglandin E2 vaginal gel as used in practice, rather than its efficacy as assessed in randomised, controlled, clinical trials. This product is used to ripen the cervix prior to induction of labour, sometimes making unnecessary the use of the standard treatment for induction, artificial rupture of the membranes (ARM) plus oxytocin. In this study, effectiveness of the gel was assessed in terms of changes in mode of delivery, and in particular the risk of Caesarean section. METHODS: An historical control was used and the risk of Caesarean section for women induced in the 1990/91 (before the introduction of the gel) was compared with that for women induced in 1992/93 (after the introduction of the gel). Maternal characteristics which may have been different in the two groups and factors which might influence the risk of Caesarean section were controlled for statistically using logistic regression, thus reducing any bias towards one group. RESULTS: After adjusting for the factors which had a significant effect on the process of labour from induction to birth, it was found that the risk of Caesarean section was not significantly lower in the 1992/93-time period, when the gel was in regular use, from that in the 2 years prior to its introduction (Odds ratio 1.09, CI95% 0.88, 1.36). CONCLUSION: Following the introduction of PGE2 gel, no difference in effectiveness, as measured in terms of mode of delivery, was detected in this study of practice, which included patients with more complex obstetric problems.

Administration, Intravaginal↗
PubMed1999

Prospective, randomized, controlled trial to determine the effect of early enhanced enteral nutrition on clinical outcome in mechanically ventilated patients suffering head injury.

OBJECTIVE: To determine the effect of early enhanced enteral nutrition (EN) on clinical outcome of head-injured patients. DESIGN: Prospective, randomized, controlled trial. SETTING: Tertiary neurosurgical and trauma center. PATIENTS: Eighty-two patients suffering head injury and requiring mechanical ventilation. INTERVENTIONS: Patients were randomized to receive standard EN (gradually increased from 15 mL/hr up to estimated energy and nitrogen requirements) or enhanced EN (started at a feeding rate that met estimated energy and nitrogen requirements) from day 1. Good neurologic outcome (Glasgow Outcome Scale score of 4 or 5) was determined at 3 and 6 months after injury, and the incidence of infective and total complications was determined during the hospital stay up to 6 months. MEASUREMENTS AND MAIN RESULTS: Disease severity assessed by best preintubation Glasgow Coma Scale score, pupillary responses, Injury Severity Score, Acute Physiology and Chronic Health Evaluation II score, computed tomographic scan categorization, and age was similar in both groups. Intervention patients had a higher percentage of energy (p = .0008) and nitrogen (p<.0001) requirements met by EN in the first week after injury. Neurologic outcome at 6 months was similar between groups, but there was a tendency for more intervention patients to have a good neurologic outcome at 3 months than control patients (61% vs. 39%, p = .08). Fewer intervention patients had an infective complication (61% vs. 85%, p = .02) or more than one total complication (37% vs. 61%, p = .046) compared with control patients. Enhanced EN was associated with a reduction in the ratio of serum concentration of C-reactive protein to albumin up to day 6 after injury (p = .004). CONCLUSIONS: Enhanced EN appears to accelerate neurologic recovery and reduces both the incidence of major complications and postinjury inflammatory responses.

Brain Injuries↗
PubMed1999

How advance directives affect hospital resource use. Systematic review of the literature.

OBJECTIVE: To assess whether advance directives influence resource use by hospitalized patients. DATA SOURCES: A systematic search of computerized medical databases, reference lists from relevant articles, and personal files was conducted to identify studies examining the association between advance directives and resource use. STUDY SELECTION: Primary studies assessing the effect of advance directives on hospital resource use were selected if they had a clear quantitative measure of hospital resource use, hospitalized patients as a study population, a control group for comparison, and a description of the advance directive being studied. Data on the following topics were abstracted from studies meeting inclusion criteria: study methods and design, resource use, source of financial data, description of advance directive, population size and composition, length of assessment. SYNTHESIS: Six studies met inclusion criteria. Three retrospective studies showed significant reductions in resource use associated with documentation of advance directives while three prospective studies (two randomized, one not randomized) showed no association between advance directives and reduced resource use. Studies were limited to narrowly defined patient populations in US tertiary care hospitals. CONCLUSIONS: Little evidence supports the hypothesis that advance directives reduce resource use by hospitalized patients. Some retrospective studies have shown savings, but their conclusions are weakened by shortcomings in study design. Prospective trials, which have better experimental methods, have demonstrated no evidence of cost savings with the use of advance directives.

Advance Directives↗
PubMed1998

A novel regulator of p21-activated kinases.

Proteins of the p21-activated kinase (Pak) family have been implicated in the regulation of gene expression, cytoskeletal architecture, and apoptosis. Although the ability of Cdc42 and Rac GTPases to activate Pak is well established, relatively little else is known about Pak regulation or the identity of Pak cellular targets. Here we report the identification of two closely related Pak3-binding proteins, possibly arising from alternative splicing, designated p50 and p85(Cool-1) (cloned out of library). Both isoforms of Cool contain a Src homology 3 domain that directly mediates interaction with Pak3 and tandem Dbl homology and pleckstrin homology domains. Despite the presence of the Dbl homology-pleckstrin homology motif, a characteristic of Rho family activators, activation of Cdc42 or Rac by Cool is not detectable. Instead binding of p50(Cool-1), but not p85(Cool-1), to Pak3 represses its activation by upstream activators such as the Dbl oncoprotein, indicating a novel mechanism of regulation of Pak signaling.

Alternative Splicing↗
PubMed1998

KH domain integrity is required for wild-type localization of Sam68.

The protein Sam68 (Src-associated in mitosis, 68 kDa) has been found to bind to SH2 and to SH3 domain-containing proteins and to RNA. Although its protein-protein interactions implicate Sam68 in cell signaling, the significance of its RNA binding remains obscure. In most cells, Sam68 shows diffuse nucleoplasmic staining. Upon treatment with transcription inhibitors, however, Sam68 localize into punctate nuclear structures. Mutant forms of mouse Sam68 were overexpressed in human cells to test the importance of the KH domain, which is required for RNA binding, in the intracellular localization of Sam68. A small deletion within the KH domain (delta 206-218) or point mutation I184N had no effect upon the localization of overexpressed Sam68. Sam68 that contained a deletion of the entire KH domain (delta KH, delta 157-256) or point mutation G178E, however, localized to distinct nuclear spots. Furthermore, delta KH Sam68, unlike wild-type Sam68 and several other mutant Sam68 proteins, did not relocalize upon poliovirus infection and caused the normally cytoplasmic viral polymerase to localize to the nuclear spots. Thus both ongoing transcription and an intact KH domain are crucial determinants of the dynamic intracellular localization of Sam68.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Validation of a lower limb model with in vivo femoral forces telemetered from two subjects.

A mathematical model of the human pelvis-leg system in the sagittal plane, with an anatomical model of the knee, was developed to calculate forces transmitted by the structural elements of the system. The model was used to study the influence of activity of hip flexors and extensors on the forces in the femur during isometric exercises and during level walking. Kinematic and kinetic data together with simultaneous electromyography (EMG) and in vivo axial forces transmitted along the prostheses from two patients implanted with instrumented massive proximal femoral prostheses were obtained. Comparison of the levels of the calculated axial forces in the model femur to the simultaneous telemetered forces showed good agreement for isometric tests. Interaction between the muscles and the bones during isometric tests was examined and bi-articular muscles were shown to play a major role in modulating forces in bones. The study supports the hypothesis that muscles balance the external limb moments, not only at joints but also along the limbs, decreasing the bending moments but increasing the axial compressive forces in bones. It is thus suggested that appropriate simulation of muscle force is necessary in in vitro laboratory experiments and in theoretical studies of load transmission in bones. The sagittal plane model underestimates the value of the maximum axial force in the femur during walking by about 30% but suggests that 70% was due to the action of the extensors or flexors. The results encourage further development of a three-dimensional model with anatomical models of the joints to include coronal and transverse planes for the study of adductors and abductors.

Evaluation Studies as Topic↗
PubMed1998

The forces in the distal femur and the knee during walking and other activities measured by telemetry.

The forces and moments in the shaft of a distal femoral replacement were measured by telemetry for a subject during different activities, and calculations were then made of the forces at the knee. The axial force showed a small peak at heel-strike followed by two main peaks during stance. In level walking, the peak axial force was between 1,487 and 1,718 N (2.2-2.5 BW), the peak shear force was 269-368 N (0.4-0.54 BW) directed anteriorly on the tibia, the peak axial torque was 7 Nm internal, while the patellofemoral force was 466-571 N. The highest axial force was recorded for descending stairs (2.8 BW). Standing on one leg produced 2.4 BW, while lying supine and raising the leg produced 1.7 BW. The data produced may resemble that of a normal subject, and has application to basic joint mechanics, to joint reconstruction, and to total knee replacement design and evaluation.

Adult↗
PubMed1998

Influence of processed corn grain in diets of dairy cows on digestion of nutrients and milk composition.

Five primiparous Holstein cows (55 d in milk) that were fitted with ruminal and duodenal cannulas were used in a 4 x 5 incomplete Latin square to determine the effects of blends of steam-flaked and dry-rolled corn on site and extent of nutrient digestion and milk yield and composition. Diets were fed as total mixed rations and consisted of 45% forage and 55% concentrate; each diet contained 27% corn grain. Dietary treatments were composed of blends of dry-rolled and steam-flaked corn in ratios of 100:0, 67:33, 33:67, and 0:100. Intake of dry matter; digestibilities of dry matter, organic matter, acid detergent fiber, cellulose, neutral detergent fiber, fatty acids, and N; and microbial efficiency were unaffected by diet. Ruminal, postruminal, and total tract digestion of starch increased linearly, and starch passage to the duodenum decreased linearly, as the proportion of dry-rolled corn in the diet decreased. Ruminal propionate and valerate increased linearly, and acetate, butyrate, isovalerate, and the acetate to propionate ratio decreased linearly, as proportions of dry-rolled corn in the diet decreased; however, no changes in total volatile fatty acid concentrations in ruminal fluid were observed. Ruminal fluid pH was similar across diets. A decrease in dry-rolled corn decreased ruminal ammonia N and plasma urea N linearly. Milk yield and composition, as well as milk N fractions, were similar across diets. Although changes in fatty acid composition of milk fat were small, linear decreases in percentages of trans-C16:1 and cis-9- and cis-10-C18:1, as well as a linear increase in the percentage of C18:2 occurred as the proportion of dry-rolled corn in the diet decreased. An increased proportion of dry-rolled corn in the diet decreased digestion of starch in the rumen, and patterns of volatile fatty acid concentrations shifted accordingly. However, no effects on lactational parameters were observed.

Ammonia↗
PubMed1998

Ash content of detergent fibers in feeds, digesta, and feces and its relevance in fiber digestibility calculations.

The influence of insoluble ash in diet, digesta, and fecal samples was evaluated. Ash-free values of neutral detergent fiber (NDF) and acid detergent fiber (ADF) for feed, digesta, and fecal samples were compared with uncorrected values of NDF and ADF in two digestibility experiments. Six feed samples were selected at random along with four duodenal and two fecal samples; the latter two were a part of two digestion studies. The silica composition of feed samples was low with the exception of oat hay and rice straw. Ash-free values of NDF and ADF for digesta and fecal samples were lower than uncorrected values of NDF and ADF, and silica accounted for the majority of the differences. The use of ash-free values of NDF and ADF in both digestibility experiments with dairy cows resulted in more realistic digestibility estimates and reduced the amount of variability associated with the calculation of the digestibility of NDF and ADF in the rumen and total digestive tract. The source of the insoluble ash was not identified but could have come from individual feedstuffs or the consumption of sand. Sample contamination by silica and other ash components may influence NDF and ADF composition if the fiber residues are not ashed prior to calculation of NDF and ADF.

Animal Feed↗
PubMed1997

Heteronuclear NMR studies of the combined Src homology domains 2 and 3 of pp60 c-Src: effects of phosphopeptide binding.

The results of heteronuclear NMR studies on the combined Src homology domains 2 and 3 (SH3-SH2) of pp60 c-Src are presented. Resonance assignments were obtained using heteronuclear triple-resonance experiments in conjunction with 15N-separated nuclear Overhauser effect spectroscopy (NOESY) data. A modified three-dimensional 13CO-15N-1H spectral correlation experiment [(HACA)CO(CA)-NH] with improved sensitivity is presented that provided additional sequential information and resolved several ambiguities. Chemical shifts and sequential- and medium-range NOE cross peaks indicate that the structures of both the SH3 and SH2 portions of the polypeptide are very similar to those of the isolated SH3 and SH2 domains. Binding of a high-affinity phosphopeptide, EPQpYEEIPIYL, induces large chemical shift changes at several locations in the SH2 domain. Comparison with known results for peptide binding to SH2 domains shows that the residues displaying the largest effects are all involved in peptide binding or undergo significant conformational changes upon binding. However, subtle changes of both 1H and 15N chemical shifts are observed for residues within the SH3 domain and the connecting linker region, indicating possible cross-domain communication.

Amino Acid Sequence↗