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Biomedical subjects

J L Taylor

Publications and source records attributed to J L Taylor.

At least 37 records · Page 2Linked to original sources

Transcranial magnetic stimulation and human muscle fatigue.

During exercise, changes occur at many sites in the motor pathway, including the muscle fiber, motoneuron, motor cortex, and "upstream" of the motor cortex. Some of the changes result in fatigue, which can be defined as a decrease in ability to produce maximal muscle force voluntarily. Transcranial magnetic stimulation (TMS) over the human motor cortex reveals changes in both motor evoked potentials (MEPs) and the silent period during and after fatiguing voluntary contractions in normal subjects. The relationship of these changes to loss of force or fatigue is unclear. However, during a sustained maximal contraction TMS evokes extra force from the muscle and thus demonstrates the development of suboptimal output from the motor cortex, that is, fatigue at a supraspinal level. In some patients with symptoms of fatigue, the response to TMS after exercise is altered, but the changed MEP behavior is not yet linked to particular symptoms or pathology.

Electric Stimulation↗

Relationship between variations in estradiol and progesterone levels across the menstrual cycle and human performance.

RATIONALE: Studies about whether or not the cognitive performance of women is influenced by changes in levels of sex steroid hormones across the menstrual cycle have produced ambiguous results. OBJECTIVES: This study tested whether flight simulator performance differs significantly between the menstrual and the luteal phase of the menstrual cycle. METHODS: In a within-subjects design, 24 female pilots were tested twice during their menstrual cycle: once during the menstrual and once during the luteal phase. On both test days they performed a 75-min simulator flight in a Frasca 141, a popular pilot training device. RESULTS: Despite highly significant differences in estradiol (E2) as well as progesterone (P) levels on the 2 test days, and despite excluding subjects with anovulatory cycles from the analyses, there were no significant differences in overall flight performance between the menstrual and luteal phases. We found no significant correlations between E2 or P levels and flight performance. CONCLUSIONS: We found no evidence that the tested menstrual cycle phases and their associated E2 and P levels significantly influence flight simulator performance. We consider these negative findings based on 24 subjects meaningful because previous studies on the influence of menstrual cycle on cognitive performance have not involved complex "real world" tasks such as piloting an aircraft and they obtained inconsistent results.

Adult↗

Nucleus accumbens muscarinic receptors in the control of behavioral depression: antidepressant-like effects of local M1 antagonist in the Porsolt swim test.

Systemically administered cholinomimetics or cholinesterase inhibitors can depress behavior in humans and animals, whereas antimuscarinic agents reverse this effect or even produce euphoria. Although these effects have been well documented, the specific brain regions that mediate them remain largely unknown. In the present experiments, muscarinic agonists and antagonists were locally injected into the nucleus accumbens of female Sprague-Dawley rats to test for their effects on behavioral depression in the Porsolt swim test and locomotor activity. Local, microinjections of the drugs in the accumbens elicited behaviors that were similar to the systemic effects reported in other studies. Injection of the non-specific agonist arecoline (40 and 80 microg) dose-dependently inhibited swimming and escape behavior. This may be mediated in part by accumbens M1 receptors because blocking these receptors with the specific antagonist pirenzepine (17.5 and 35.0 microg) did the opposite by increasing swimming. Gallamine (0.13, 0.44, and 0.88 microg), an antagonist at M2 receptors, dose-dependently decreased swimming. Two-way microdialysis suggested that this was in part due to the release of ACh by blocking M2 autoreceptors. Scopolamine, a mixed M1/M2 receptor antagonist, also released ACh but did not decrease swimming, probably because the M1 receptors were blocked; the drug (1.0 microg) increased swimming time, much like pirenzepine. With the exception of arecoline, none of the drugs significantly affected locomotor activity in a photocell cage. Arecoline (40 microg), which had decreased swimming, reduced activity. The present study suggests that muscarinic receptors in the nucleus accumbens can control immobility in the Porsolt swim test. The onset of immobility may depend on the activation of post-synaptic M1 receptors.

Acetylcholine↗

COX-1 inhibitory activity in extracts from Eucomis L'Herit. species.

Non-steroidal anti-inflammatory compounds can relieve pain and inflammation associated with elevated levels of prostaglandins in the body and are proposed to be the agents responsible for the action of traditional herbal remedies associated with the reduction of pain, fever and inflammation. Primarily the bulbs and in some instances the leaves and roots, of Eucomis L 'Herit. species are widely utilized in South African traditional medicine for this purpose. A measure of the anti-inflammatory activity of plant extracts can be generated using the cyclooxygenase (COX-1) assay. High levels of COX-1 inhibitory activity were detected in crude extracts prepared from the leaves, bulbs and roots of Eucomis species. Of the 11 species tested, 9 species exhibited moderate COX-1 inhibitory activity (40-70%) for the aqueous bulb extracts. All 11 species showed COX-1 inhibitory activity of +/-70% or higher, for the ethanol bulb extracts. The bulb and root extracts (ethanol) showed, in general, the highest levels of COX-1 inhibitory activity, but most species exhibited no significant difference in activity between plant parts. Generally (for 7 of the 11 species), these levels did not differ significantly in specimens harvested in summer and in winter. IC50 values were calculated to be 72 microg ml(-1) for the bulb extract of E. autumnalis autumnalis, and 27 microg ml(-1) for the root extracts. The corresponding IC50 value for the leaf extract was estimated to be 15 microg ml(-1). The COX-1 inhibitors were relatively stable over time, both in solution (ethanol) and in the dried plant material. Extracts tested over a period of three years did not differ significantly in COX-1 inhibitory activity. These experimental results validate the extensive use of this plant in southern African traditional medicine.

Anti-Inflammatory Agents, Non-Steroidal↗

Measuring outcomes of care for adolescents with emotional and behavioral problems.

OBJECTIVES: To validate the prototype Adolescent Treatment Outcomes Module (ATOM), examine its sensitivity to clinical change, and determine its feasibility for administration in routine clinical settings. METHOD: A sample of 67 adolescents, aged 11 through 18, was selected from new patients at two inpatient and two outpatient mental health programs. Adolescents and parents completed the ATOM and validating instruments at intake, 1 week postintake, and again at 6 months. RESULTS: Nine self-report symptoms predicted positive diagnoses of oppositional defiant, conduct, anxiety, and depressive disorders on the basis of structured diagnoses, with sensitivities of 0.7 to 0.8. Test-retest correlations for outcome scales were largely excellent (>0.70). Scales that measured functioning at home, in school, and in the community were moderately correlated in the expected direction with global functioning. Decreases in symptom severity and functional impairment were generally associated with decreases in validating instruments. Administration time averaged 25 minutes for adolescents and 28 minutes for parents. CONCLUSIONS: Both parents and adolescents readily completed the ATOM. Module scales demonstrated excellent reliability and good to fair concurrent validity. The ATOM was able to detect change and its absence.

Activities of Daily Living↗

Development of a method for mRNA differential display in filamentous fungi: comparison of mRNA differential display reverse transcription polymerase chain reaction and cDNA amplified fragment length polymorphism in Leptosphaeria maculans.

We modified a technique, cDNA-AFLP, for identifying differentially expressed genes in plants to work in the filamentous fungus Leptosphaeria maculans (Desmaz.) Ces. & De Not. The cDNA fragments generated by our method ranged in size from approximately 100 to 400 bps. On average, twice as many cDNA fragments were amplified per primer set with cDNA amplified fragment length polymorphism in comparison with mRNA differential display reverse transcription polymerase chain reaction. The DNA fragments of interest were excised from gels and analyzed by single-stranded conformation polymorphism to eliminate nondifferentially expressed cDNA contamination. The method was used to examine gene expression differences between cultures grown in the presence or absence of an analog of the Brassica phytoalexin brassinin. Eleven of the fourteen fragments examined were determined by reverse Northern blot to be differentially expressed. In examining gene expression differences between young cultures not producing sirodesmins and older cultures that were producing these phytotoxins, we found 17 of 25 fragments were differentially expressed. Northern blots with these fragments confirmed the results.

Ascomycota↗

Influence of the menstrual cycle on flight simulator performance after alcohol ingestion.

OBJECTIVE: Previous studies investigating the influence of the menstrual cycle on cognitive functioning of women after alcohol ingestion have obtained inconsistent results. The present study tested the hypothesis that flight simulator performance during acute alcohol intoxication and 8 hours after drinking differs between the menstrual and the luteal phase of the menstrual cycle. METHOD: White female pilots (N = 24) were tested during the menstrual and the luteal phases of their menstrual cycles. On each test day they performed a baseline simulator flight, consumed 0.67 g/kg ethanol, and performed an acute-intoxication and an 8-hour-carryover simulator flight. RESULTS: Subjects reached highly significant increases in estradiol (E2) as well as progesterone (P) levels during the luteal test day. Yet, there were no significant differences in overall flight performance after alcohol ingestion between the menstrual and luteal phases during acute intoxication or at 8-hour carryover. We found no correlations between E, or P levels and overall flight performance. However, there was a statistically significant Phase x Order interaction: Pilots who started the experiment with their menstrual day were less susceptible to the effects of alcohol during the second test day than were pilots who started with their luteal day. CONCLUSIONS: The tested menstrual cycle phases and varying E2 and P levels did not significantly influence postdrink flight performance. Because the present study included a comparatively large sample size and because it involved complex "real world" tasks (piloting an aircraft), we believe that the present findings are important. We hope that our failure to detect menstrual cycle effects will encourage researchers to include women in their investigations of alcohol effects and human performance.

Adult↗

Regulation of nitric oxide synthase 2 in rabbit corneal cells.

PURPOSE: The purpose of these studies was to investigate the role of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin 1beta (IL-1beta), and transforming growth factor-beta (TGF-beta) in the regulation of inducible nitric oxide synthase (NOS2) activity in rabbit corneal cells. METHODS: Rabbit corneal epithelial, stromal, and endothelial cells were grown in culture and treated with cytokines and growth factors, alone or in combination. NOS activity was measured at times up to 72 hours after treatment by assaying the culture medium for nitrite using the Griess reaction. Cell lysates were analyzed by Western blot analysis for NOS2 protein. RNA was isolated and amplified with NOS1-, NOS2-, and NOS3-specific primers by RT-PCR. RESULTS: NOS2 expression was induced by combined cytokine treatment from nondetectable levels to abundant levels in low passage (<4) stromal cells and to low levels in corneal endothelial cells but not in corneal epithelial cells. In the absence of IFN-gamma, little or no nitrite accumulation was induced by TNF-alpha, IL-1beta, or lipopolysaccharide (LPS) treatment. The inductive effects of IFN-gamma were antagonized in a dose-dependent manner by the myxoma virus rabbit IFN-gamma receptor homolog, M-T7. rRaIFN-gamma, in combination with IL-1beta and TNF-alpha, induced the appearance of NOS2 mRNA within 24 hours but detectable nitrite did not accumulate in large amounts (>10 microM) until after 24 hours postinduction. NOS2 was identified as a 130 kDa protein on Western blot analysis using monoclonal antibody against murine NOS2. TGF-beta(1) and beta(2) inhibited the accumulation of cytokine-induced nitrite in a dose-dependent manner while not significantly reducing the steady state level of NOS2 mRNA. The activity of the induced NOS was inhibited by 1400W, a NOS2-selective inhibitor, but not 7-nitroindazole, a NOS1-selective inhibitor. CONCLUSIONS: In cultured corneal stromal cells, NOS2 expression was upregulated by IFN-gamma in combination with IL-1beta and TNF-alpha but not by any of these cytokines alone, while TGF-beta downregulated the activity. Cultures of corneal epithelial cells could not be induced to express NOS2, yet cultures of endothelial cells produced low amounts of NO in response to cytokines. The NOS1 and NOS3 isoforms were not detected in any of these corneal cells.

Animals↗

Ischaemia after exercise does not reduce responses of human motoneurones to cortical or corticospinal tract stimulation.

Motor unit firing rates and voluntary activation of muscle decline during sustained isometric contractions. After exercise, the responses to motor cortical and corticospinal stimulation are reduced. These changes may reflect motoneuronal inhibition mediated by group III and IV muscle afferents. To determine whether the post-contraction depression of the responses to corticospinal or motor cortical stimulation could be maintained by continued firing of ischaemically sensitive group III and IV muscle afferents, we examined responses in muscles that were held ischaemic after exercise. Following a sustained maximal voluntary contraction (MVC) of the elbow flexors lasting 2 min, the response to stimulation of the corticospinal tract was reduced but the usual recovery (over approximately 2 min) was not delayed when the muscles were maintained ischaemic for 2 min after the contraction. Following a sustained MVC, the time course of the reduction in the response to motor cortical stimulation (a gradual decrease over approximately 2 min, maintained for > 10 min) was also not altered if the muscle was held ischaemic. Mean arterial blood pressure rose to 155 +/- 12 mmHg during the 2 min MVC, declined to 125 +/- 9 mmHg immediately after it, but remained at this level without returning to pre-exercise levels (102 +/- 10 mmHg) until circulation to the arm was restored. This confirms that the sustained MVC activated a reflex dependent on group III and IV muscle afferents. This study shows that ischaemically sensitive group III and IV muscle afferents do not mediate depression of responses to motor cortical or corticospinal stimulation after fatiguing exercise. It also suggests that firing of such afferents does not directly inhibit motoneurones or motor cortical output cells.

Adult↗

Transcranial magnetic stimulation (TMS) in controlled treatment studies: are some "sham" forms active?

BACKGROUND: Carefully designed controlled studies are essential in further evaluating the therapeutic efficacy of transcranial magnetic stimulation (TMS) in psychiatric disorders. A major methodological concern is the design of the "sham" control for TMS. An ideal sham would produce negligible cortical stimulation in conjunction with a scalp sensation akin to real treatment. Strategies employed so far include alterations in the position of the stimulating coil, but there has been little systematic study of their validity. In this study, we investigated the effects of different coil positions on cortical activation and scalp sensation. METHODS: In nine normal subjects, single TMS pulses were administered at a range of intensities with a "figure eight" coil held in various positions over the left primary motor cortex. Responses were measured as motor-evoked potentials in the right first dorsal interosseus muscle. Scalp sensation to TMS with the coil in various positions over the prefrontal area was also assessed. RESULTS: None of the coil positions studied met the criteria for an ideal sham. Arrangements associated with a higher likelihood of scalp sensation were also more likely to stimulate the cortex. CONCLUSIONS: The choice of a sham for TMS involves a trade-off between effective blinding and truly inactive "stimulation." Further research is needed to develop the best sham condition for a range of applications.

Adult↗

Changes in muscle afferents, motoneurons and motor drive during muscle fatigue.

Fatigue is a reduction of maximal muscle force or power that occurs with exercise. It is accompanied by changes at multiple levels in the motor pathway and also by changes in the discharge patterns of muscle afferents. Changes in afferent firing can lead to altered perceptions and can also act on the efferent pathway. Changes in the motor pathway include slowing of motor unit firing rates during sustained maximal voluntary contractions (MVCs). Muscle responses to stimulation at different levels of the motor pathway also change. Transcranial magnetic stimulation of the motor cortex and stimulation of descending tracts in the spinal cord in human subjects show an increase in the response of the cortex and a decrease in response of the motoneuron pool during sustained MVCs. In addition, the silent period following magnetic stimulation is prolonged. During relaxation after fatiguing exercise, muscle responses to stimulation of the motor cortex are initially facilitated and are then depressed for many minutes, whereas responses to descending tract stimulation are initially depressed but recover over about 2 min. Although some of the loss of force of fatigue does occur through inadequate drive to the muscle, it is not clear which, if any, of the changes described in the cortex or the motoneurons are responsible for loss of maximal voluntary force and thus contribute to fatigue. Changes may be associated with muscle fatigue without causing it.

Animals↗

Plant part substitution--a way to conserve endangered medicinal plants?

Population growth, urbanization and the unrestricted collection of medicinal plants from the wild is resulting in an over-exploitation of natural resources in southern Africa. Therefore, the management of traditional medicinal plant resources has become a matter of urgency. In southern Africa the most frequently used medicinal plants are slow-growing forest trees, bulbous and tuberous plants, with bark and underground parts being the parts mainly utilized. A strategy which would satisfy the requirements of sustainable harvesting, yet simultaneously provide for primary health care needs, would be the substitution of bark or underground parts with leaves of the same plant. This paper outlines the concept of plant substitution, using preliminary results of our recent investigations into four of the most important and most threatened South African medicinal plants - Eucomis autumnalis (bulb), Siphonochilus aethiopicus (rhizome), Ocotea bullata (bark), and Warburgia salutaris (bark) - as a demonstration of the kind of research necessary. Extracts of various plant parts were compared chemically using TLC-analysis, and pharmacologically in terms of antibacterial activity and cyclooxygenase-1 inhibition in vitro. The importance of the concept of plant part substitution as a strategy for the conservation of medicinal plants in southern Africa is discussed in terms of the results obtained.

Africa, Southern↗

Interferon coordinately inhibits the disruption of PML-positive ND10 and immediate-early gene expression by herpes simplex virus.

Interferons (IFNs) are important components of the innate immune response, limiting herpes simplex virus (HSV) infection. In recombinant HSV-infected cells, IFN inhibited expression of beta-galactosidase from the immediate-early gene, ICP4, promoter. The extent of inhibition was dependent on IFN dose, IFN type, cell type, and multiplicity of infection (moi). IFN inhibited gene transcription, leading to a complete block in ICP4 promoter-driven gene expression in 90% of cells. The same IFN treatments resulted in an increase in the size and number of nuclear domain 10 (ND10) structures that stained positive by immunofluorescence for the promyelocytic leukemia (PML) protein. In cultures infected at low moi with a recombinant HSV producing ICP4 as a fusion protein with green fluorescence protein, the appearance of green fluorescence in the nucleus coincided with loss of PML-positive ND10 in the same nucleus, even in the rare ICP4-expressing IFN-treated cells. IFN-dependent inhibition was nearly complete when the immediate-early promoter was in the viral genome but was minimal when the promoter was stably integrated into the cellular genome. These data reveal that IFN can completely block viral gene expression in infected cells and that enhancement of the ND10 structure, which is the site of initiation of HSV replication, correlates with the block in viral gene expression.

Acetamides↗

Toward a level playing field: predictive factors for the outcomes of mental health treatment for adolescents.

OBJECTIVE: To understand better the effectiveness of routine treatment for emotional and behavioral problems experienced by adolescents, methods are needed to control for between-provider differences in the distribution of factors that adversely affect treatment success. Such methods are necessary to fairly compare providers' outcomes and to aid clinicians in identifying adolescents for whom routine care may need to be altered. As a preliminary step toward developing a model to adjust treatment outcomes to account for predictive factors, findings from studies of treated samples of adolescents were reviewed to identify the factors that influence the likelihood of treatment success for this population. METHOD: Medline and PSYCInfo databases were searched for studies of treated adolescents that reported the association between expert-nominated predictive factors and outcomes. Thirty-four studies met inclusion criteria. RESULTS: Significant predictors identified in these studies include diagnosis, baseline severity of symptoms and functional impairment, family dysfunction, and previous treatment. Several expert-nominated factors have not been adequately studied in treated samples. CONCLUSIONS: Much basic work is needed before a convincing body of empirical evidence can explain predictive factors for adolescent mental health treatment outcomes. Future efforts should determine a reduced set of predictive factors that can be measured with minimal burden to providers.

Adolescent↗

Supraspinal fatigue during intermittent maximal voluntary contractions of the human elbow flexors.

Responses to transcranial magnetic stimulation in human subjects (n = 9) were studied during series of intermittent isometric maximal voluntary contractions (MVCs) of the elbow. Stimuli were given during MVCs in four fatigue protocols with different duty cycles. As maximal voluntary torque fell during each protocol, the torque increment evoked by cortical stimulation increased from approximately 1.5 to 7% of ongoing torque. Thus "supraspinal" fatigue developed in each protocol. The motor evoked potential (MEP) and silent period in the elbow flexor muscles also changed. The silent period lengthened by 20-75 ms (lowest to highest duty cycle protocol) and recovered significantly with a 5-s rest. The MEP increased in area by >50% in all protocols and recovered significantly with 10 s, but not 5 s, of rest. These changes are similar to those during sustained MVC. The central fatigue demonstrated by the torque increments evoked by the stimuli did not parallel the changes in the electromyogram responses. This suggests that part of the fatigue developed during intermittent exercise is "upstream" of the motor cortex.

Adult↗

How can we learn about developmental processes from cross-sectional studies, or can we?

OBJECTIVE: Cross-sectional studies are often used in psychiatric research as a basis of longitudinal inferences about developmental or disease processes. While the limitations of such usage are often acknowledged, these are often understated. The authors describe how such inferences are often, and sometimes seriously, misleading. METHOD: Why and how these inferences mislead are here demonstrated on an intuitive level, by using simulated data inspired by real problems in psychiatric research. RESULTS: Four factors with major roles in the relationship between cross-sectional studies and longitudinal inferences are selection of time scale, type of developmental process studied, reliability of measurement, and clarity of terminology. The authors suggest how to recognize inferential errors when they occur, describe how to protect against such errors in future research, and delineate the circumstances in which only longitudinal studies can answer crucial questions. CONCLUSIONS: The simple conclusion is that one must always use the results of cross-sectional studies to draw inferences about longitudinal processes with trepidation.

Aging↗

Relationship of CogScreen-AE to flight simulator performance and pilot age.

OBJECTIVES: We report on the relationship between CogScreen-Aeromedical Edition (AE) factor scores and flight simulator performance in aircraft pilots aged 50-69. METHODS: Some 100 licensed, civilian aviators (average age 58+/-5.3 yr) performed aviation tasks in a Frasca model 141 flight simulator and the CogScreen-AE battery. The aviation performance indices were: a) staying on course; b) dialing in communication frequencies; c) avoiding conflicting traffic; d) monitoring cockpit instruments; e) executing the approach; and f) a summary score, which was the mean of these scores. The CogScreen predictors were based on a factor structure reported by Kay (11), which comprised 28 CogScreen scores. Through principal components analysis of Kay's nine factors, we reduced the number of predictors to five composite CogScreen scores: Speed/Working Memory (WM), Visual Associative Memory, Motor Coordination, Tracking, and Attribute Identification. RESULTS: Speed/WM scores had the highest correlation with the flight summary score, Spearman r(rho) = 0.57. A stepwise-forward multiple regression analysis indicated that four CogScreen variables could explain 45% of the variance in flight summary scores. Significant predictors, in order of entry, were: Speed/WM, Visual Associative Memory, Motor Coordination, and Tracking (p<0.05). Pilot age was found to significantly improve prediction beyond that which could be predicted by the four cognitive variables. In addition, there was some evidence for specific ability relationships between certain flight component scores and CogScreen scores, such as approach performance and tracking errors. CONCLUSIONS: These data support the validity of CogScreen-AE as a cognitive battery that taps skills relevant to piloting.

Aerospace Medicine↗