Biomedical subjects

G Smith

Publications and source records attributed to G Smith.

At least 415 records · Page 23Linked to original sources

PubMed1994

mu-Opioid receptor stimulation of inositol (1,4,5)trisphosphate formation via a pertussis toxin-sensitive G protein.

The cellular mechanisms underlying opioid action remain to be fully determined, although there is now growing indirect evidence that some opioid receptors may be coupled to phospholipase C. Using SH-SY5Y human neuroblastoma cells (expressing both mu- and delta-opioid receptors), we demonstrated that fentanyl, a mu-preferring opioid, caused a dose-dependent (EC50 = 16 nM) monophasic increase in inositol (1,4,5)trisphosphate mass formation that peaked at 15 s and returned to basal within 1-2 min. This response was of similar magnitude (25.4 +/- 0.8 pmol/mg of protein for 0.1 microM fentanyl) to that found in the plateau phase (5 min) following stimulation with 1 mM carbachol (18.3 +/- 1.4 pmol/mg of protein), and was naloxone-, but not naltrindole- (a delta antagonist), reversible. Further studies using [D-Ala2, MePhe4, Gly(ol)5]enkephalin and [D-Pen2,5]enkephalin confirmed that the response was specific for the mu receptor. Incubation with Ni2+ (2.5 mM) or in Ca(2+)-free buffer abolished the response, as did pretreatment (100 ng/ml for 24 h) with pertussis toxin (control plus 0.1 microM fentanyl, 26.9 +/- 1.5 pmol/mg of protein; pertussis-treated plus 0.1 microM fentanyl, 5.1 +/- 1.3 pmol/mg of protein). In summary, we have demonstrated a mu-opioid receptor-mediated activation of phospholipase C, via a pertussis toxin-sensitive G protein, that is Ca(2+)-dependent. This stimulatory effect of opioids on phospholipase C, and the potential inositol (1,4,5)trisphosphate-mediated rises in intracellular Ca2+, could play a part in the cellular mechanisms of opioid action.

Calcium↗

PubMed1994

Pseudophakes experience apparent minification in an imaging display.

Apparent minification of virtual images has been attributed to accommodation micropsia, that is, a reduction in the apparent size of viewed objects accompanying an inward accommodation of the eyes. Thirteen bilateral pseudophakes incapable of accommodation but with good residual vision were tested monocularly for apparent minification in the viewfinder of a single-lens reflex camera. Apparent minification of about the same order as that typically found with normals occurred with the pseudophakic observers, demonstrating that pseudophakes are subject to distortions in apparent size with virtual-imaging displays in the same way as normals, thus establishing that visual accommodation is not a necessary condition for the effect.

Accommodation, Ocular↗

PubMed1994

The effects of experimental malnutrition on albumin metabolism and distribution in rabbits.

In order to determine the extent to which the concentration of albumin in plasma is maintained at the expense of the extravascular pool during protein-energy malnutrition, the rates of exchange between albumin in plasma (IA) and the extravascular pool (EA) and consequently the distribution of albumin between intravascular and extravascular pools (expressed as EA:IA) were measured in protein-energy-depleted and control rabbits. The fractional rates of synthesis (FSR) and catabolism (FCR), the concentration of albumin and the plasma volume (PV) were also measured. In animals in which protein-energy intake was reduced by 58% the concentration of albumin in plasma remained unchanged, whereas FCR decreased by 38% and FSR by 30%. No significant changes in EA:IA or PV were found. We conclude that albumin concentration during protein-energy depletion is not maintained at the expense of extravascular albumin, but by parallel changes in the rates of catabolism and synthesis.

Algorithms↗

PubMed1994

Empirical prediction of physiological response to prolonged work in encapsulating protective clothing.

Work in moderate or hotter environments while wearing encapsulating protective clothing (PC) results in heat storage and substantial diminution of work productivity, as well as being a potential health risk. An ability to predict the responses of workers using PC would be very useful. Predictions were made of work times at 21 degrees C of 15 subjects performing prolonged hard work (450 W gross) while wearing PC, based upon prior measures of short-duration bench stepping in PC and heart rate responses. A simple model was derived that shows good potential for predicting work time in moderate temperatures in PC; Total Time = 7.2 (bench step duration) - 34 (bench comfort) + 4 (height); R2 = 0.83, C.V. = 13. Unexpectedly, models that incorporated recovery heart rate as a variable were not as effective. With further refinement, the prediction approach tested in this study would be immediately useful for managing military and civilian personnel working in PC. Additionally, it could be utilized at minimal cost during routine training.

Adult↗

PubMed1994

An optical technique for the measurement of thoracic wall movement during high-frequency jet ventilation.

Instrumentation for use in high-frequency jet ventilation is not currently capable of providing information suitable for predicting gas exchange. Whilst techniques for the accurate measurement of tidal volume during jet ventilation are now available, the relationship between tidal volume and the efficiency of gas exchange varies with frequency and inspiratory/expiratory time (I:E) ratio. We report technical details of a new non-invasive instrument capable of accurately measuring displacement of the thoracic wall at high frequencies and without electrical connection to the patient. It is hoped that use of this instrument will allow the calculation of an efficiency index for the transduction of airway pressure changes into peripheral expansion. It is also hoped that this index may be of value in predicting the gas exchange response to changes in jet parameters.

Equipment Design↗

PubMed1994

Pain in hospitalized patients with AIDS: analgesic and psychotropic medications.

OBJECTIVE: We undertook this study to evaluate the use of analgesic and psychotropic medication in acquired immunodeficiency syndrome (AIDS) patients with pain and to determine whether our previous findings of a high prevalence of pain in patients with AIDS who were hospitalized could be replicated. Additional factors related to pain were evaluated, such as death during hospital stay, i.v. drug abuse, and length of hospital stay. DESIGN: One hundred thirty-nine medical charts randomly selected from 1 year of hospital admissions of patients with AIDS were reviewed in a systematic manner for pain, prescription of analgesic and psychotropic medication, patient demographics, and disease characteristics. RESULTS: Sixty-one percent of the charts reviewed had at least one note of nonprocedural pain. Sixty-eight percent of pain patients were prescribed a nonnarcotic (most commonly acetaminophen), and 44% a narcotic. Sixty-two percent of pain patients were prescribed a psychotropic medication. Patients with pain were significantly more likely to receive an analgesic as well as psychotropic medication, particularly a sedative-hypnotic, than patients without pain. Having pain was not significantly related to other factors such as i.v. drug abuse except for length of hospital stay. Most of the previous study findings were replicated with the notable exception of the rate of prescription of psychotropics as well as acetaminophen, which increased substantially in this study. CONCLUSIONS: Although pain is a prevalent problem in hospitalized AIDS patients, narcotics as well as antidepressants appear to be underutilized. It is suggested that medical education regarding pain management in AIDS patients is an important first step in a more aggressive approach.

Acquired Immunodeficiency Syndrome↗

PubMed1994

The role that binocular vision and stereopsis have in evaluating fundus features.

PURPOSE: We report two experiments that address the role of stereopsis in viewing the fundus. METHODS: Thirteen observers viewed stereo slides obtained by lateral displacement of a fundus camera. We quantified the capacity of seven clinicians (normal stereopsis) to resolve depth in a model eye viewed monocularly and binocularly. We also compared the ability of the same seven and six additional clinicians (with reduced stereopsis) to determine the relative position of the cup shown in normal and reverse disparity as well as answering a questionnaire. We determined optimal performance based on a schematic eye. RESULTS: Monocular viewing gives better than expected results with binocularity being of greatest benefit for small disparities. Clinicians perform much worse in stereoscopic judgments than predicted by calculation. Few clinicians report making stereo depth judgments in practice. All amblyopic observers report using hyperacuity cues. CONCLUSION: This study shows that binocularity and stereopsis are beneficial for judging small disparities under limited circumstances. The level of stereopsis achieved in practice fails to approach the expected limit. We believe that this constriction arises from a known limit to stereo acuity associated with extended fields.

Adult↗

PubMed1994

PrP genotype and agent effects in scrapie: change in allelic interaction with different isolates of agent in sheep, a natural host of scrapie.

Man and sheep are the two species in which spongiform encephalopathies occur naturally, and in which there are recognized genetic components that predispose an individual person or sheep to clinical disease. In both species mutations/polymorphisms in the PrP gene have been linked to the incidence of natural disease, but only in sheep is it possible to investigate by deliberate exposure to infection whether these polymorphisms are directly correlated with survival time. Cheviot sheep of different PrP genotypes were challenged with one of two isolates of scrapie or an isolate of bovine spongiform encephalopathy and the survival time and incidence of disease were monitored. Genotype analysis showed that dimorphisms in codons 136 and 171 of the ovine PrP gene correlated with control of disease incidence and modulation of incubation time. Crucially, the functional effects of these domains of PrP were shown to alternate depending on the isolate of infecting agent.

Alleles↗

PubMed1994

An efficient oxygen independent two-photon photosensitization mechanism.

A novel oxygen-independent photosensitization mechanism from the upper triplet state (Tn) of rose bengal has been demonstrated by selectively populating Tn by sequential two-color laser excitation. Products formed from Tn inhibit red blood cell acetylcholinesterase and decrease viability of P388D1 mouse macrophage monocyte cells as measured by trypan blue exclusion assay. Laser flash photolysis studies indicate that Tn reacts efficiently, as evidenced by permanent photobleaching of T1 absorption, with chemical yields approaching unit efficiency. This mechanism may have application for oxygen deficient photosensitization under high intensity, pulsed laser irradiation.

Acetylcholinesterase↗

PubMed1994

Comparative evaluation of chemiluminescent DNA probe assays and exoantigen tests for rapid identification of Blastomyces dermatitidis and Coccidioides immitis.

Chemiluminescent DNA probe (Accuprobe) assays developed by Gen-Probe, Inc. (San Diego, Calif.), for the rapid identification of Blastomyces dermatitidis and Coccidioides immitis were evaluated and compared with the exoantigen test by using 74 mycelial cultures of B. dermatitidis and 72 mycelial cultures of C. immitis. Seventeen isolates of the dimorphic pathogen Paracoccidioides brasiliensis were included because of their gross morphologic and antigenic relatedness to B. dermatitidis. The heterologous fungi, namely, species of Chrysosporium, which are often confused with B. dermatitidis, and species of Malbranchea, which morphologically resemble C. immitis, were tested. All 74 of the B. dermatitidis mycelial isolates were correctly identified by the Accuprobe assay for B. dermatitidis within 2 h. However, the B. dermatitidis probe cross-hybridized with rRNA extracts of 10 of the 17 P. brasiliensis isolates, misidentifying them as B. dermatitidis. All 72 of the C. immitis isolates were identified correctly with the C. immitis probe. None of the other heterologous fungi belonging to Chrysosporium spp., Malbranchea spp., Onychocola canadensis, and Geotrichum sp. were cross-reactive with the B. dermatitidis and C. immitis probes. The exoantigen tests specifically identified 74 B. dermatitidis, 72 C. immitis, and 17 P. brasiliensis isolates within 48 to 72 h and differentiated the related heterologous fungi from the three dimorphic fungal pathogens.

Animals↗

PubMed1994

Left ventricular mass and cardiovascular reactivity in young men.

The relation between left ventricular wall thickness and mass, arterial plasma catecholamines, and blood pressure at rest and during a mental arithmetic challenge and a cold pressor test was examined in 69 healthy men 19 years of age. The subjects were recruited from the 1st (n = 21), 50th (n = 26), and 99th (n = 22) percentiles in mean blood pressure. All underwent echocardiography to determine mean wall thickness and left ventricular mass. Continuous intra-arterial blood pressure, electrocardiogram, and arterial sampling of plasma catecholamines were performed after 30 minutes of supine rest, during a 5-minute mental arithmetic challenge, and during a 1-minute cold pressor test. Stepwise multiple-regression analyses considering mean wall thickness and left ventricular mass as the dependent variables were applied. Intra-arterial systolic blood pressure (r = .54, P < .0001) and arterial plasma epinephrine (r = .31, P = .009) after 30 minutes of supine rest were the only independent explanatory variables of mean wall thickness (multiple R2 = .33, P < .0001). Blood pressure at screening and during mental stress and cold pressor tests were not independent explanatory variables. The present study suggests that resting arterial blood pressure and plasma epinephrine may be of importance for development of left ventricular hypertrophy.

Adult↗

PubMed1994

Effects of haloperidol challenge on regional cerebral glucose utilization in normal human subjects.

OBJECTIVE: Positron emission tomography and the fluorodeoxyglucose (FDG) method were used to determine the brain's metabolic response to neuroleptic challenge in a normal, disease-free state. METHOD: FDG measurements were obtained before and 12 hours after administration of 5 mg of haloperidol to 12 young normal men. These values were compared with test-retest FDG measures obtained from nine normal male control subjects who received no drug intervention. RESULTS: After haloperidol administration, the haloperidol subjects showed significantly lower glucose utilization in the neocortex, limbic cortex, thalamus, and caudate nucleus but not in the putamen or cerebellum. After adjustment for global effects, significant reductions were still evident in the frontal, occipital, and anterior cingulate cortex, whereas the putamen and cerebellum showed significant increases. CONCLUSIONS: This study, measuring the brain's metabolic response to acute receptor blockade, is a first step in the development of an assay of CNS pharmacological activity. By determining the response to neuroleptic challenge in a normal state, the study establishes a comparison group for determining response to challenge in various psychiatric conditions.

Adult↗

PubMed1994