A dose-dependent enhancement of muscarinic activation of phospholipase C by halothane in SH-SY5Y cells.
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Biomedical subjects
Publications and source records attributed to G Smith.
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We describe a method for measurement of the sensitivity of upper airway reflexes. The technique is based upon delivery of an irritant chemical stimulus (dilute concentrations of ammonia vapour) to the upper airway. The technique is non-invasive and uses equipment which is portable, allowing measurements to be made in the clinical environment.
In a double-blind, cross-over study, we have investigated the effect of oral diazepam 20 mg and placebo on the sensitivity of upper airway reflexes in 10 male volunteers (aged 25-35 yr). Upper airway reflex sensitivity (UARS) was assessed using small concentrations of ammonia vapour as a stimulus to upper airway receptors. A threshold concentration of ammonia, at which reflex glottic closure occurred in response to the ammonia stimulus, was used as a measure of UARS. With diazepam, there was significant depression of UARS from 30 to 150 min after administration.
We have recorded the threshold concentration of inhaled ammonia vapour required to elicit reflex glottic closure (NH3TR) in 102 healthy, nonsmoking volunteers (39 female) aged 17-96 yr in order to assess the effect of age upon upper airway reflex sensitivity. A single measurement of sensitivity was made in each subject using a system delivering small concentrations of ammonia vapour for single intermittent breaths to the upper airway and recording glottic closure using an inspiratory pneumotachograph. We found a strong positive correlation between age and NH3TR, indicating a decrease in upper airway reflex sensitivity with increasing age.
OBJECTIVE: To examine the correlation between childhood psychological trauma(s) and refractory back pain in patients with and patients without prior spine surgery. DESIGN: Retrospective chart review survey of 101 consecutive patients who had undergone multidisciplinary evaluation for refractory back pain. SETTING: Private practice, tertiary care spine center. MAIN OUTCOME MEASURES: Each psychological risk factor (physical abuse, sexual abuse, emotional neglect or abuse, abandonment, and chemically dependent caregiver) was rated as present or absent. Spinal pathology was graded as significant or not significant. RESULTS: There were 56 patients with failed back surgery syndrome, 28 men and 28 women, with a mean age of 43 and mean pain duration of 45 months. There were 45 patients with no prior surgery, 26 men and 19 women, with a mean age of 43 and mean pain duration of 33 months. In the failed back surgery syndrome group, 27 (48%) had three or more risks and 39 (70%) had two or more. When the 12 patients with significant pathology are not considered, 24 of the remaining 44 (55%) patients had three or more risks. In the group with no prior surgery, 26 (58%) had three or more risks and 38 (84%) had two or more. When the five patients with significant pathology are not considered, 24 (60%) had three or more risks. CONCLUSIONS: Multiple childhood psychological traumas may predispose a person to chronic low back pain. In patients in this setting with refractory low back pain with or without prior lumbar spine surgery, three or more childhood psychological risk factors are prevalent, especially in patients with minimal structural pathology.
Simple formulas based on reduced eyes have been developed to predict the variation in longitudinal chromatic aberration with variation in ametropia or accommodation. Two formulas were developed, one for axial ametropia and one for refractive ametropia. The latter also served as a model for accommodation. The results using the formulas are in close agreement with results obtained using raytracing through more sophisticated models. Combining the results of different methods gives the following predictions of change in chromatic difference of focus, between wavelengths of 400 and 700 nm, with change in each diopter of refractive error or accommodation: axial ametropia 0.012 to 0.017 D (0.6 to 0.9%), refractive ametropia 0.05 D (2.2 to 2.4%), and accommodation 0.04 to 0.05 D (2.1 to 2.6%). The chromatic aberration effects of correcting lenses with low dispersion are intermediate in effect and opposite in sign to the effects of corresponding degrees of axial ametropia and refractive ametropia.
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Thirty top level athletes, 30 athletic students and 30 sedentary controls underwent electrocardiographic and echocardiographic investigation. Resting ECG in athletes showed increased indices of hypertrophy compared to controls. The echocardiographic examination demonstrated an increase in left ventricular mass (LVM) of 47% in top athletes and 23% in athletic students compared to controls. The relationship between wall thickness and diameter was similar in all groups, as were parameters of systolic and diastolic left ventricular function at rest. There was no correlation between LVM assessed by echocardiography and ventricular ectopic activity assessed by Holter monitoring in this normotensive population. Highly significant correlations between ECG and echocardiographic parameters of hypertrophy were demonstrated.
Compartmental analysis of Strongloides stercoralis burdens in experimentally infected, serially necropsied dogs was used to test an autoinfective burst hypothesis. The hypothesis states that in well-established, active infections and in chronic infections as well, the rate of larval development is down-regulated so that most larvae do not attain infectivity internally. The majority pass in the feces as preinfective, rhabditiform larvae, but a few (those with the most rapid developmental rate) attain infectivity internally, and therefore are positioned for autoinfectivity. In contrast, in immunologically naive hosts, larval development proceeds without host hindrance and many larvae, proceeding at the most rapid rate of a spectrum of normal intrinsic developmental rates, attain infectivity internally. For a brief period, hyperinfection occurs, during which the adult worm population increases sharply. Gut-level resistance soon occurs, larval development is retarded, and an increasing proportion of larvae are discharged as preinfective rhabditiform larvae. With fewer larvae developing to infectivity internally, recruitment into the adult population decreases, with an attendant increase in the mean age and a gradual decrease in the size of the adult population. The data and the attendant model strongly support this autoinfective burst hypothesis.
Provider spoke with corporate executives about the trends changing the face of long term care. They talked about a variety of tools--quality initiatives, diversification, financing, and staff recruitment--that are having an impact on the industry.
OBJECTIVE: To determine the variability in human papillomavirus (HPV) DNA testing of the cervix in young women found positive for HPV DNA by dot blot hybridization on routine examination. METHODS: Young women who were found to be HPV DNA-positive on routine screening using an RNA-DNA dot blot hybridization method were asked to return for repeat HPV DNA sampling, cytology, colposcopic examination, and biopsy if indicated. Those who had no histologic evidence of cervical dysplasia were asked to return every 4 months for cytology and HPV DNA testing using standardized RNA-DNA hybridization and polymerase chain reaction techniques. RESULTS: The women were followed for a mean of 27.6 months (range 13-40) with a mean of six visits (range four to ten). One-third of the women remained consistently or intermittently HPV DNA-positive by RNA-DNA dot blot hybridization, and almost 50% of the women remained consistently or intermittently positive using polymerase chain reaction techniques. Women were more likely to be positive by polymerase chain reaction than by RNA-DNA hybridization at both 1 year and after 2 years of follow-up (P < .05). However, rates for persistent positive tests by either method were similar at 1 and 2 years of follow-up. Forty percent of the subjects had new or different types than the original HPV type appear during follow-up. All five women who had evidence of spontaneous regression of cytologic abnormalities became HPV DNA-negative by both methods. CONCLUSIONS: Our data suggest that a portion of women infected with HPV appear to eliminate the infection over a relatively short period and are at low or no risk of developing disease. Persistent DNA negativity was also found in those women undergoing spontaneous regression. However, a substantial proportion of women remained intermittently positive by RNA-DNA hybridization and polymerase chain reaction. This finding suggests that the virus remains latent in some individuals and may undergo reactivation, defined by sufficient replication to allow detection by means less sensitive than polymerase chain reaction.
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We present a novel strategy for increasing the level of functional mammalian cytochrome P450 (Cyt.P450) and NADPH:cytochrome P450 reductase enzymes produced in yeast. A cDNA encoding the rat P450 reductase was modified by the addition of a sequence coding for the N-terminal region of P450 reductase from Saccharomyces cerevisiae. The addition of this hydrophobic tail greatly increased the apparent stability of the reductase protein produced in S. cerevisiae, as compared to the unmodified rat P450 reductase. When the rat hybrid reductase was produced simultaneously with one of two mammalian Cyt.P450s, the rat CYP2B1 or the human CYP2A6, there was a significant increase in the specific activity of each of the Cyt.P450s. The optimization of this approach and its extrapolation to other organisms should lead to a marked improvement in our ability to study and exploit the P450 system.
A major goal of current candidate malaria vaccines is to stimulate the expansion of clones of malaria-specific lymphocytes. We have examined the in vitro T cell responses of a group of malaria exposed and non-exposed adult Caucasian donors to recombinant circumsporozoite (CS) proteins, one of which is undergoing clinical trials, to blood-stage parasites, and to synthetic peptides copying the CS protein and defined blood-stage proteins. In nearly all individuals tested, CD4 T cell proliferation or lymphokine production occurred in response to whole parasite or CS protein stimulation, and T cells from many individuals responded to synthetic peptides. T cell responses were major histocompatibility complex-restricted, and stimulation of T cells with malaria parasites or CS protein did not appear to expand a population of T cell receptor gamma/delta cells. Malaria-specific responses were independent of prior malaria exposure, and in some cases exceeded the magnitude of response to tetanus toxoid. Specific T cells are present in high frequency in the peripheral blood of many donors who have never been exposed to malaria. Although malaria-specific CD4 T cells play an important role in immunity, these data question whether vaccines need to stimulate such cells, and focus attention on other aspects of malaria immunity which may be more critical to a successful vaccine.
Synovial fluid PLA2 concentration was measured by an ELISA technique using monoclonal antibodies raised against human recombinant "synovial-type" group II phospholipase A2. This ELISA was specific for synovial-type PLA2 and did not detect pancreatic (group I) PLA2. In all synovial fluids examined, including rheumatoid, osteoarthritic, psoriatic, and gouty fluids, synovial fluid PLA2 enzyme activity significantly correlated with PLA2 immunoreactivity (P < 0.001). Within the limits of the ELISA technique, there was no evidence for the presence of specific or nonspecific modulation of PLA2 activity by either putative PLA2 activating or inhibitory proteins.