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Biomedical subjects

C A Lewis

Publications and source records attributed to C A Lewis.

At least 55 records · Page 3Linked to original sources

Inhibitory synaptic transmission in isolated patches of membrane from cultured rat spinal cord and medullary neurons.

1. To quantify the variability in the characteristics of inhibitory glycinergic and GABAergic currents at single synaptic connections between cultured rat embryonic spinal cord or medullary neurons, we have used patch-clamp techniques to record miniature inhibitory postsynaptic currents (mIPSCs) in cell-attached patches. Experiments were performed with the patch pipette containing either a low-calcium internal saline to allow comparison with subsequent whole cell recordings or external saline with tetrodotoxin, DL-2-amino-5-phosphonovaleric acid, and 6-cyano-7-nitroquinoxaline-2,3-dione, a solution that is more appropriate for bathing a nerve terminal. 2. The mIPSCs recorded from the synapses restricted to the cell-attached patches were characterized by their times to peak, amplitudes, and time constants of decay. The degree of variability in these characteristics was quantified with the use of the following model-independent parameters: the coefficient of variation, skewness, and kurtosis. The distribution of time to peak values has a mean value of 5.6 +/- 0.5 (SE) ms, has the lowest coefficient of variation (0.33 +/- 0.01), is fairly symmetrical, and has a Gaussian shape with respect to peakedness. On the other hand, both the amplitude and decay time constant distributions are highly skewed and more peaked than Gaussian distributions. The mean amplitude is -6.6 +/- 0.6 pA with a coefficient of variation of 0.60 +/- 0.05, whereas the mean decay time constant is 22.8 +/- 1.0 ms with a coefficient of variation of 0.81 +/- 0.03. 3. The amplitude distributions for spontaneous inhibitory currents recorded from cell-attached patches are best fitted by the sum of multiple Gaussians. The coefficient of variation for the first Gaussian peak fitted to the amplitude distributions is 0.290 +/- 0.028. 4. Decay time distributions were consistently best fitted by the sum of four Gaussians with decay constants as follows: D1 = 5.7 +/- 0.2 ms (n = 12), D2 = 11.2 +/- 0.7 ms (n = 11), D3 = 20.6 +/- 0.8 ms (n = 12), and D4 = 43.8 +/- 2.3 ms (n = 16). These mean values are essentially identical to those reported in the preceding paper for mIPSCs recorded in the whole cell configuration. 5. In eight neurons we were able to record mIPSCs both in cell-attached patches and in subsequent whole cell configurations. The properties of mIPSCs recorded from single synapses (i.e., times to peak, amplitude, and time constants of decay) show as much variability as those of mIPSCs recorded subsequently in the whole cell mode; that is, there are no statistically significant differences in the coefficients of variation, skewness, or kurtosis for the three different distributions.

Animals↗

Giant, TTX-insensitive, inhibitory postsynaptic currents in cultured rat spinal cord and medullary neurons.

1. In whole cell patch-clamp studies on cultured rat embryonic spinal cord and medullary neurons bathed in tetrodotoxin, DL-2-amino-5-phosphonovaleric acid, and 6-cyano-7-nitroquinoxaline-2,3-dione, large and long-lasting spontaneous inhibitory postsynaptic currents were occasionally recorded. The amplitudes of these events were 1 order of magnitude larger than those of spontaneous miniature inhibitory postsynaptic currents. Because these large currents had reduced amplitudes in calcium-free saline and in solutions containing glycinergic or GABAergic antagonists, we conclude that they were probably produced by large and prolonged release of glycine and/or 4-amino-n-butyric acid (GABA), which subsequently bind to their postsynaptic receptors. 2. The frequency of spontaneous miniature postsynaptic currents increased dramatically during the long, slow decay phase of these large postsynaptic currents. Considering the requirement for extracellular calcium for the occurrence of these large responses, we hypothesize that this increased frequency reflected an increased intracellular calcium concentration in the presynaptic terminal. 3. Similar evidence for large inhibitory postsynaptic currents and prolonged transmitter release was observed in cell-attached patches, which also exhibited the smaller, spontaneous miniature inhibitory postsynaptic currents, suggesting that these large events are properties of single synaptic terminals. 4. A comparison of the properties of these large inhibitory postsynaptic currents recorded in whole cell mode or cell-attached patches showed no statistically significant differences. The overall mean values, then, are 13.9 +/- 1.6 (SE) ms and 4.5 +/- 0.5 s for the 10-90% rise time and duration, respectively. Furthermore, these large events had amplitudes that were 11-fold larger than the mean amplitude of the miniatures (i.e., mean amplitude ratio of 10.8 +/- 0.5). 5. Periodic large increases in the frequency of spontaneous miniature inhibitory postsynaptic currents occurred in both cell-attached patches and in the whole cell mode, and these increases were only sometimes associated with the large inhibitory postsynaptic currents. The rhythmicity in both recording configurations had similar temporal characteristics, with average interburst intervals of 5 and 12-14 s. Presumably these bursts of spontaneous miniature postsynaptic currents reflected periodic oscillations in the Ca2+ concentration in presynaptic terminals. 6. Both the probability and the frequency of occurrence of large inhibitory postsynaptic currents doubled during the 7-day period of time in culture when experiments were performed, suggesting that these large currents may play a role during development.

Animals↗

Convergent validity of the depression-happiness scale with the Crown-Crisp experimental index.

In recent years the study of subjective well-being has attracted much research interest. A 1993 operational definition is the Depression-Happiness Scale of McGreal and Joseph. The aim of the present research was to investigate the convergent validity of the Depression-Happiness Scale with the Crown-Crisp Experiential Index. Among 40 undergraduate university students, higher scores on the Depression-Happiness Scale were significantly associated with lower scores on Free floating anxiety (-.63), Somatic anxiety (-.56), Depression (-.78), and Hysteria (-.36) scales but not the Phobic anxiety (-.27) or Obsessionality (-.25) scales of the Crown-Crisp Experiential Index. These data provide further evidence for the convergent validity of the Depression-Happiness Scale.

Adult↗

Influence of spasmogen inhalation by guinea pigs upon subsequent demonstration of ovalbumin-induced hyperreactivity in isolated airways tissues.

Guinea pigs were sensitized with ovalbumin (i.p.) 14 days before use. In vivo airway hyperreactivity induced by ovalbumin inhalation was determined by challenging with aerosolized spasmogen (5-hydroxytryptamine [5-HT] methacholine, the thromboxane-mimetic, U-46619, or adenosine) 24 hr before (7 days with adenosine) and again 18-24 hr after the ovalbumin inhalation. One hour later they were killed and isolated airways perfused lung halves and tracheal spirals were set up for determination of tissue sensitivity to carbachol, histamine, and adenosine. This study examines whether the spasmogen interferes with the ovalbumin-induced in vitro hyperreactivity and the combined effects of ovalbumin followed by spasmogen challenge upon tissue sensitivity. The influence of the spasmogen upon the in vitro measurement of ovalbumin-induced hyperreactivity was variable, depending upon which spasmogen was used and whether the lung or trachea was examined. The inhalation of the spasmogen in ovalbumin-challenged guinea pigs had clear effects upon the subsequent measurement of tissue sensitivity. This depended upon the spasmogen used, but 5-HT, methacholine, and U-46619 usually depressed responsiveness, while adenosine was without significant effect. As a consequence, the appearances of in vitro hyperreactivity due to the ovalbumin challenge could be masked (e.g., bolus doses of agonist in the trachea when 5-HT was the spasmogen) or the degree of hyperreactivity could be enhanced (e.g., in the perfused lung when adenosine was the spasmogen). Thus, isolated airways tissues should not be used for evaluating tissue sensitivity when the animals have been previously exposed to inhalations of spasmogens.

Adenosine↗

A method of measuring fluid balance during transurethral resection of the prostate.

OBJECTIVE: To design a practical system for non-invasively monitoring fluid balance during transurethral resection of the prostate (TURP) and other endoscopic procedures. MATERIALS AND METHODS: Load cell transducers are incorporated into a platform placed under the operating table. Output is passed to a digital weighmeter and then to a portable computer. The raw data is filtered using software written by the authors (CAL) and the output displayed both numerically and graphically on the computer screen. The device was tested under laboratory conditions and then assessed in the clinical setting. RESULTS: The device proved stable in both the laboratory and clinical settings. Examples of the common patterns generated during TURP are presented. The prototype has been used routinely in our practice to warn the surgeon and anaesthetist of fluid overload and has been used to monitor fluid balance in several studies. CONCLUSIONS: This instrument provides a practical method of monitoring total fluid balance during TURP. It can be used with either general or regional anaesthesia and provides information not otherwise available. It provides an early warning of significant changes in total fluid balance, particularly irrigant fluid absorption. Use of this device serves to prevent development of the TUR syndrome, a potentially fatal complication of endoscopic surgery. Our ultimate aim is to produce a refined version that is simple, compact and cheap enough to be used routinely in all urological theatres. The cost of a single episode of intensive care for a patient developing iatrogenic complications from irrigant absorption would offset the cost of such a device.

Absorption↗

Airway hyper- or hyporeactivity to inhaled spasmogens 24 h after ovalbumin challenge of sensitized guinea-pigs.

1. The aim of this study was to determine whether an inhalation of ovalbumin (OA, 10 or 20 mg ml-1) by conscious OA-sensitized guinea-pigs leads to airway hyperreactivity to spasmogens 24 h later. In contrast to most previous studies, the spasmogens (5-HT, methacholine (MCh), U-46619 and adenosine) were administered by inhalation and airway function was measured in conscious guinea-pigs. 2. Guinea-pigs were sensitized by i.p. injection of 10 micrograms OA and 100 mg aluminium hydroxide in 1 ml normal saline; 14-21 days later they were exposed to an inhalation of 5-HT, MCh, U-46619 or adenosine. Specific airway conductance (sGaw) was measured in conscious animals by whole body plethysmography. The spasmogens caused bronchoconstriction, measured as a reduction in sGaw from the pre-inhalation basal values. Dose-related bronchoconstrictions were observed with 5-HT, MCh and U-46619. 3. The effect of an ovalbumin macroshock challenge upon the responses to each spasmogen were examined by giving an inhalation of aerosolized OA at 24 h (or 7 days in the cause of adenosine) after an initial spasmogen challenge. Eighteen to twenty-four hours after the OA macroshock, the same guinea-pigs were exposed to a repeated inhalation of 5-HT, MCh, U-46619 or adenosine. 4. U-46619 was the only spasmogen to demonstrate hyperresponsiveness, the peak change in sGaw being increased from -12.3 +/- 9.9 to -38.8 +/- 5.0% by 10 mg ml-1 OA challenge. In contrast, the ovalbumin challenge (20 mg ml-1) inhibited the bronchoconstrictions to 5-HT (50 micrograms ml-1) and MCh (100 micrograms ml-1). Adenosine demonstrated bronchoconstriction in sensitized guinea-pigs but no significant change in the response was observed after an OA challenge. 5. All results were compared with a control group of sensitized guinea-pigs receiving a NaCl challenge. The bronchoconstrictor responses to 5-HT, MCh, U-46619 or adenosine did not differ significantly before and after the saline challenge, indicating reproducibility of the responses. 6. In further experiments, guinea-pigs were exposed to inhalation of 5-HT (50 micrograms ml-1) or MCh (300 micrograms ml-1) 24 h before atropine (10 micrograms, 100 micrograms or 1 mg ml-1) and again at 0.5 to 1.5 h afterwards. Atropine, antagonized the 5-HT- and MCh-induced bronchoconstrictions over the same antagonist dose-range. This suggests that the bronchoconstriction induced in the conscious guinea-pig by 5-HT is mediated primarily via muscarinic receptors, possibly by a vagal reflex. The inhibition of the responses to 5-HT and MCh by OA challenge would therefore appear to be related to interference with a common cholinergic pathway for these spasmogens. 7. In summary, airway hyperresponsiveness was evident at 24 h after OA challenge as measured by an enhanced bronchoconstrictor response to inhaled U-46619. When 5-HT or MCh were used as the spasmogens, an opposing decrease in responsiveness was observed. This was presumed to be due to an inhibition of cholinergic pathways by the OA challenge. Adenosine caused a bronchoconstriction in the sensitized animals but this was not enhanced by the OA challenge.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Factor analysis of the Center for Epidemiological Studies-Depression Scale.

The Center for Epidemiological Studies-Depression Scale is one of the most popular instruments for survey work with the general population. A 1993 study by Thorson and Powell reported a 5-factor solution. The present study was undertaken to replicate these findings; however, factor analysis with varimax rotation based on the responses of 187 students yielded 4 factors of depressed affect, somatic disturbance, positive affect, and interpersonal difficulties. Although these data do not replicate the 5-factor work of Thorson and Powell, they do largely confirm the previous research.

Adolescent↗

Convergent validity of the Depression-Happiness Scale with measures of happiness and satisfaction with life.

The aim of the present paper was to investigate the internal reliability and convergent validity of the McGreal and Joseph (1993) Depression-Happiness Scale with measures of happiness and satisfaction with life. Subjects were 63 undergraduate students attending the University of Ulster. Internal reliability of the scale was .91, and higher scores on the scale were associated with scores on the other measures indicating greater happiness and satisfaction with life.

Adolescent↗

Authoritarianism and projection.

To extend the 1995 work of McCollaum and Lester, 378 undergraduate students were administered the conservatism scale of the Wilson-Patterson Attitude Inventory and the projection scale of the Defense Style Questionnaire-40. No significant association was found between scores on conservatism and projection.

Adult↗

Non-specific airway hyperreactivity in isolated respiratory preparations from guinea-pigs sensitized and challenged with ovalbumin.

Airway hyperreactivity to physical, chemical, immunological and pharmacological stimuli is well documented in vivo. The aim of this study was to investigate whether tissues taken from guinea-pigs that had been shown to display hyperreactivity in vivo after antigen challenge were also hyperreactive in vitro. Isolated airway-perfused lungs from ovalbumin-sensitized guinea-pigs challenged 24 h beforehand with an aerosol of ovalbumin showed a significant (P < 0.05) increase in responsiveness to the bronchoconstrictor response to a bolus dose of carbachol (10 micrograms) when compared with saline challenged animals. The contractile responses to single doses of carbachol (10 micrograms) and histamine (30 micrograms) in immersed tracheal spiral preparations taken from sensitized animals exposed to the ovalbumin were also significantly enhanced (P < 0.05). A non-significant leftward shift was observed in the concentration-response curve for histamine in challenged perfused lungs from ovalbumin-challenged animals compared with an NaCl challenge. Concentration-response curves to carbachol and histamine in immersed tracheal spirals were virtually superimposed. Therefore, this study has shown non-specific airway hyperreactivity of isolated airway perfused lungs at 24 h following a challenge of sensitized guinea-pigs with aerosolized ovalbumin, although this was not evident from concentration-response curves in immersed trachea. The isolated perfused lung therefore provides a simple method for further evaluation of the mechanisms of airway hyperreactivity.

Adenosine↗

Religiosity and obsessionality: the relationship between Freud's "religious practices".

Freud (1907/1961) outlined parallels between obsessive actions and religious practices, describing how both neurotic and religious practice serve as defensive, self-protective measures involved in the repression of instinctual impulse. Freud also described some differences between the two concepts. To examine these observations, measures of religiosity (the Francis Scale of Attitudes Towards Christianity; Francis & Stubbs, 1987) and obsessional traits and symptoms (the Sandler-Hazari Obsessionality Inventory; Sandler & Hazari, 1960) were administered (N = 139). In both male and female samples, significant correlations were found between the measure of religiosity and obsessional traits but not between religiosity and obsessional symptoms. The results support previous findings linking religiosity and obsessional traits but suggest that differences between religious practices and obsessive actions are greater than their similarities. These findings further illuminate the general relationship between the Francis Scale of Attitudes Towards Christianity and personality.

Adult↗

Plasma homocyst(e)ine, folate, and vitamin B-12 concentrations and risk for early-onset coronary artery disease.

High plasma homocyst(e)ine (Hcy) concentrations may be a determinant of coronary artery disease (CAD). Folate and vitamin B-12 are required for the primary metabolic pathway to reduce Hcy concentrations. The interrelationships of Hcy and these two vitamin cofactors were investigated in a case-control study of 101 white males aged 30-50 y with angiographically demonstrated CAD, and 108 white male, similarly aged, control subjects living in the same community as the patients. The odds ratio (OR) of CAD per quartile increase of plasma Hcy concentration based on control values was 1.6 (95% CI: 1.3, 2.1). After age, HDL and LDL cholesterol, body mass index, smoking, hypertension, and diabetes were controlled for, Hcy remained an independent risk factor (OR: 1.4; 95% CI: 1.0, 2.0). The OR change per quartile increase of folate concentration was 0.8 (95% CI: 0.6, 1.0). This difference was reduced (OR: 0.9; 95% CI: 0.7, 1.2) after Hcy adjustment. No difference in the geometric mean of vitamin B-12 concentration was found between patients and control subjects, both 5.8 nmol/L. However, after Hcy and the other CAD risk factors were controlled for, the OR per quartile increase in vitamin B-12 concentration was 1.5 (95% CI: 1.0, 1.8). Reduction in plasma Hcy by interventions to increase plasma folate concentration may decrease CAD risk.

Adult↗

Identification of a locus, distinct from RDS-peripherin, for autosomal recessive retinitis pigmentosa on chromosome 6p.

We performed a genomic search for linkage to autosomal recessive retinitis pigmentosa in a large pedigree obtained from the Dominican Republic using microsatellite markers. Regions of the genome known to contain genes for retinitis pigmentosa were preferentially tested. One of these regions, on chromosome 6p, which contains the gene for peripherin, gave positive lod scores. Use of a mononucleotide repeat polymorphism in the peripherin gene excluded this locus. Two- and multi-point analyses suggest that the most likely location for the disease gene is near D6S291, which is located approximately 20 centimorgans telomeric from peripherin.

Chromosomes, Human, Pair 6↗