The gamma-aminobutyric acid receptor of Ascaris as a target for anthelmintics.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
R J Martin
Publications and source records attributed to R J Martin.
Relationship of pulse oximetry to arterial oxygen tension in infants.
Pulse oximetry is a useful technique for noninvasive oxygen monitoring in sick infants. We simultaneously measured oxygen saturation by pulse oximetry and on arterial blood samples by co-oximetry as well as PaO2 and the relative content of fetal (F) and adult hemoglobin in order to evaluate the reliability of pulse oximetry. Comparisons were made in triplicate in ten infants with acute cardiorespiratory disease less than 7 days of age and in 11 infants with chronic lung disease greater than 28 days of age. Oxygen saturation pulse oximetry and arterial saturation were well correlated over a wide range of saturation values. In infants with chronic lung disease, PO2 derived from pulse oximetry was within 10 torr of measured PaO2 in 73% of comparisons. In contrast, calculated PaO2 was within 10 torr of measured PaO2 in only 50% of comparisons in patients with acute disorders. The chronic infants all had less than 10% hemoglobin F, but in the acute infants, hemoglobin F ranged from 26% to 83%. Nonetheless, correction of oxygen dissociation curves for type of hemoglobin in these acute infants failed to improve the correlation between calculated and measured PaO2. We conclude that pulse oximetry saturations and their derived PaO2 values correlated well with measured arterial saturation and PaO2 obtained from arterial blood samples in neonates with chronic lung disease and prolonged oxygen dependence. In infants with acute cardiorespiratory problems, pulse oximetry unreliably reflects PaO2, but may be useful in detecting clinical deterioration.
Evaluation Studies as Topic↗
Enzyme activities in regions of the hypothalamus.
The activities of certain key enzymes have been measured in the ventral medial and ventral lateral areas of the hypothalamus, which are implicated in feeding behaviour, and compared with enzyme activities in the cortex and brainstem. The enzymes measured are concerned with glucose metabolism [hexokinase (EC 2.7.1.1) and glucose-6-phosphate dehydrogenase (EC 1.1.1.49)], ketone body metabolism [3-hydroxybutyrate dehydrogenase (EC 1.1.1.30)], fatty acid utilisation [carnitine palmitoyl transferase (EC 2.3.1.7)], citric acid cycle activity [pyruvate dehydrogenase (EC 1.2.4.2) and citrate synthase (EC 4.1.3.7)] and neurotransmitter synthesis [glutamate dehydrogenase (EC 1.4.1.3)].
Animals↗
A high-conductance calcium-dependent chloride channel in Ascaris suum muscle.
The properties of a high-conductance Ca-dependent Cl channel in the body muscle membrane of the nematode parasite Ascaris suum were examined with the patch-clamp technique. In Ascaris Ringer solution the current-voltage relationships of the channel appeared linear during hyperpolarization with a slope conductance of 200 pS (in symmetrical 175 mM-Cl): during depolarization the slope conductance reduced. Cation and anion replacement experiments showed this channel to be permeable to Cl ions. In artificial perienteric fluid (in symmetrical 78 mM-Cl) the channel conductance was found to be 114 pS. Subconductance states were seen when the patch was depolarized. The channel conductance showed saturation with increasing Cl concentrations. The channel was voltage sensitive: the probability of the channel being open and the mean open time of the channel reduced when the patch was depolarized. Mean channel open times between 2.4 and 215 ms were observed. Frequency histograms of the distributions of open and closed times were fitted with two and three exponentials respectively; this suggests complex channel kinetics with multiple open and closed states. Ca applied to the intracellular surface of the patch increased in a dose-dependent manner the number and probability of the channels being open. These channels were seen in about 20% of all patches and occasionally up to 15 channels were seen in a single patch. The distributions of the probabilities of seeing N channels open in multichannel patch records were not not always well fitted by the binomial distribution: it is suggested that adjacent channels could have different probabilities of being open. The possible functions of this channel are discussed.
Animals↗
Single-channel currents from zona-free mouse eggs.
Cell-attached patch recordings were made from zona-free mouse eggs to examine currents at the single-channel level; two types were identified. A channel with a mean conductance of 130 pS showed changes in reversal potential on dilution of the patch pipette solution consistent with a cation channel; the channel current persisted when the only cation in the pipette was K+: it was concluded that this channel was permeable to K+. The binomial distribution was used to describe the proportion of time 0, 1, 2, ..., n channels were open in multichannel recordings of the K+ channel. Bursts of inward currents of about 1 pA, which showed voltage activation and could be recorded in the presence of CsCl and tetraethylammonium (TEA), were identified as Ca2+ channels.
Animals↗
Transient changes in expiratory time during hypercapnia in premature infants.
The transient ventilatory responses to hypercapnia were studied in nine healthy preterm infants. We administered 4% CO2 in air for at least 7 min during quiet sleep and measured frequency (f), inspiratory time (TI), expiratory time (TE), tidal volume (VT), and minute ventilation (VI). Frequency increased over the first 2 min of CO2 inhalation (P less than 0.05) and then decreased to control values (P less than 0.05). This response was secondary to changes in TE, which decreased over the first 2 min (P less than 0.05) and then returned to control values, whereas TI did not change. The late increase in TE was associated with an increased percent of breaths exhibiting retardation of expiratory flow (braking) (P less than 0.05). These breaths had longer TE than the breaths without braking (P less than 0.05). Exponential curves made to fit the increases in VI and VT revealed that only 67% of the infants reached 90% of steady state for both VI and VT over the 7-min study period. The time to 90% of steady state was always shorter for VI than VT (P less than 0.05) due to the transient changes in f. The results indicate that the transient changes of f in response to hypercapnia are secondary to changes in TE, which appear unique to human infants. We speculate that the expiratory braking that develops during the course of CO2 inhalation increases lung volume, resulting in prolongation of TE via mechanoreceptor-mediated reflexes.
Humans↗
Serum and lipoprotein lipids of fetal pigs and their dams during gestation as compared with man.
Serum and lipoprotein (LP) lipids were measured in fetal pigs and their dams during gestation. In the 2nd trimester (70 days of gestation), fetal lipids resembled those of their dams. Early in the 3rd trimester (90 days) total serum concentrations of cholesterol (CH), triglyceride (TG) and free fatty acids (FFA) were lower in fetuses than in sows (p less than 0.01), but the decreases were not expressed uniformly among the LP classes. By the middle of the 3rd trimester (100 days) fetal serum lipids had declined further, and the distribution of TG (but not CH) between the LP fractions was significantly different from the distribution in sows (p less than 0.01). Sow serum CH, TG and FFA varied, but did not change significantly from days 70 to 100 of gestation; there was a tendency for sow serum lipids to increase, particularly FFA. Distributions of TG and CH in sow LP were unchanged by pregnancy. Results suggest that independent fetal regulation of lipid metabolism develops during the last half of gestation, and that lipid metabolism (especially TG) may be altered during fetal life. Changes in sow lipids during gestation were much less pronounced than in humans, but fetal patterns were similar.
Animals↗
Influence of food intake during late gestation on serum lipids of sows and their progeny.
Serum and lipoprotein lipids were quantified in pregnant and nonpregnant sows allowed restricted and ad libitum access to a low-fat cholesterol-free diet, and in the progeny of these sows. Pregnant sows exhibited a mild increase in serum triglycerides in the third trimester, reflecting an increase in very low density lipoprotein (VLDL)-triglyceride concentration. Ad libitum feeding enhanced this increase. Free fatty acids were depressed in mid-pregnancy (60 days gestation), but were normal or elevated in the final trimester. Total cholesterol was similar in all groups. Pregnancy and level of food intake interacted to increase VLDL-cholesterol in pregnant sows fed ad libitum. Pregnancy decreased high density lipoprotein cholesterol. Level of food intake by sows had no influence on serum lipid concentrations of newborn pigs. Distribution of cholesterol and triglyceride between lipoprotein classes was different in newborn pigs when compared to sows. These results imply fetal self-regulation of lipid metabolism during late gestation. Sow serum lipids are not identical to those in humans. However, when fed a modified diet that resembles a human diet, sows may be useful as a model for humans in studies of lipid metabolism during pregnancy.
Animals↗
Control of laryngeal muscle activity in preterm infants.
Control of upper airway muscles, such as those in the larynx, appears important for optimizing airflow patterns during normal respiration. Electromyograms (EMGs) of the laryngeal (LAR) area and diaphragm (DIA) were recorded with esophageal and skin electrodes, respectively, in 12 unsedated sleeping preterm infants during changes in chemical and mechanical feedback. Onset of phasic inspiratory LAR EMG preceded both DIA EMG and inspiratory airflow by 70 +/- 60 and 180 +/- 80 ms, respectively. Inhalation of 4% CO2 increased both peak LAR and DIA EMGs but did not alter their temporal relationships. End expiratory occlusion prolonged both LAR (600 +/- 120 to 930 +/- 290 ms, p less than 0.05) and DIA EMGs (690 +/- 180 to 940 +/- 270 ms, p less than 0.005) as well as mechanical inspiratory time. Early braking of expiratory flow was accompanied by persistence of DIA EMG into the expiratory phase, while termination of mid- to late expiratory braking was associated with onset of the LAR EMG of the subsequent inspiration. We conclude that respiratory activity of the LAR EMG is altered by both chemical and mechanoreceptor stimulation. Furthermore, simultaneous recording of LAR and DIA EMGs suggests that upper airway and chest wall muscles have different effects on expiratory flow patterns in human infants.
Administration, Inhalation↗
Genioglossus response to airway occlusion in apneic versus nonapneic infants.
The ability to maintain pharyngeal patency is compromised in infants who have apneic episodes associated with airway obstruction. Since the genioglossus (GG) muscle is thought to be important in maintaining pharyngeal patency, we measured the GG EMG with sublingual surface electrodes during unobstructed breathing and in response to end-expiratory airway occlusion. Studies were performed in nine premature infants with mixed and obstructive apnea and in eight nonapneic control infants. Phasic GG EMG was usually absent during normal tidal breathing in both groups of infants, however, GG activity typically appeared during airway occlusion. The response of the GG muscle during airway occlusion differed between control and apneic infants. During the first three occluded inspiratory efforts, control infants had 42 +/- 5, 74 +/- 5, and 80 +/- 5% (mean +/- SEM) of their occlusions associated with a GG EMG response, respectively. In contrast, apneic infants had significantly fewer (13 +/- 4, 38 +/- 9, and 52 +/- 9%) occlusions associated with a GG EMG response. There was a delay in onset of the GG EMG when compared to the onset of the diaphragm EMG and initial negative esophageal pressure swing, but this delay decreased with each subsequent appearance of the GG EMG in both infant groups. Infants with mixed and obstructive apnea thus have decreased activation of their GG in response to occlusion which may reflect their inability to recruit dilating muscles of the upper airway during spontaneous airway obstruction.
Airway Obstruction↗
Pre-adipocyte proliferation and differentiation in response to hormone supplementation of decapitated fetal pig sera.
Growth hormone and thyroid hormones have been implicated as important serum factors for adipocyte development in cell culture. Fetal decapitation removes these factors from serum of the growing fetal pig and results in development of fewer adipocytes than in intact fetuses. These experiments examined the effects of growth hormone or thyroxine supplementation to decapitated fetal pig sera upon pre-adipocyte proliferation and differentiation. Hormones were supplemented to concentrations present in sera from intact pig littermates (reference). Sera +/- hormones were analyzed for their effects upon pre-adipocyte proliferation as determined by [3H]-thymidine incorporation; enzyme expression as determined by sn-glycerol-3-phosphate dehydrogenase activity; and induction of complete differentiation into lipid filled adipocytes as based upon a pre-adipocyte proliferation and enzyme expression than reference sera. Growth hormone had no effect in decap sera upon these parameters. Decap sera permitted detection of 54% more lipid-accumulating, newly formed adipocytes on percol gradients than reference sera, but growth hormone reduced detection to 29% of reference sera. Thyroxine specifically stimulated pre-adipocyte proliferation more than decap sera, but not to the level of reference sera. Complete differentiation, a formation of lipid-accumulating adipocytes was promoted also by thyroxine in comparison to basal decap sera. The results of these experiments indicate thyroid hormones are an important component of fetal sera for regulation of adipocyte development, whereas growth hormone may only affect cellular metabolism and not promote pre-adipocyte growth and development.
Adipose Tissue↗
Central endocrine regulation of the development of hormone responses in porcine fetal adipose tissue.
Experiments were performed to determine whether central endocrine or neural regulation is primarily involved with the development of endocrine responses in fetal adipose tissue metabolism. Fetuses within one uterine horn were either decapitated (decap) or spinally cauterized at 45 d of gestation, with fetuses in the other horn serving as sham controls (intact). Fetuses were removed by cesarean section at 110 d of gestation. Slices of subcutaneous adipose tissue (100 mg) were incubated in media supplemented with radioactive glucose and insulin (1.0 mU/ml) to measure the metabolic response of the tissue to insulin. Other slices were incubated in medium supplemented with norepinephrine bitartrate (1 microgram/ml) to measure lipolytic response by glycerol release. Basal glucose utilization for oxidation, total lipid and fatty acid synthesis was higher in decap adipose tissue than intact adipose tissue. Cauterized and intact fetuses did not differ in adipose tissue glucose metabolism. Only decap adipose tissue demonstrated an insulin stimulation of glucose oxidation and lipogenesis. Norepinephrine stimulated lipolysis in both cauterized and intact adipose tissue but had no effect upon decap adipose tissue lipolysis. These results demonstrate central endocrine regulation but not central neural regulation has an important function in the development of porcine fetal adipose tissue metabolism and its responses to systemic hormones.
Adipose Tissue↗
Tracheostomy tube failure in obstructive sleep apnea.
In our institutions we routinely do posttracheostomy sleep studies on patients being treated for obstructive sleep apnea. We have identified several patients who failed to show objective evidence of improvement after tracheostomy. From our studies we have found that both mechanical obstruction and concomitant respiratory control dysfunction caused this failure. A unique tracheostomy tube was constructed to treat the subset of patients with internal collapse of the tracheostomy tube.
Adult↗
Metabolic characteristics of skeletal muscle from lean and obese Zucker rats.
The purpose of this study was to determine if the metabolic response to obesity and to pair feeding of obese Zucker rats to lean Zucker rats was similar across skeletal muscles. Oxidation of glucose, palmitate and isoleucine was studied in muscle strips in vitro using appropriate 14- carbon substrates as tracers. The plantaris muscle was subjected to histochemical analyses using an alkaline actomyosin ATPase, NADH-tetrazolium reductase and an oil red 0 stain. Soleus muscles from both ad libitum and pair fed obese rats oxidized less glucose to CO2, but released similar amounts of lactate when compared to the soleus muscles of lean rats. Oxidation of glucose was similar in the extensor digitorum longus (EDL) muscle of ad libitum fed obese rats, but lower when pair fed to the intake of lean rats. No differences were apparent in palmitate oxidation to CO2 or in incorporation into lipid (both soleus and EDL muscles), except in the EDL muscle of pair-fed obese rats which exhibited a higher rate for palmitate metabolism when compared with lean rats. Isoleucine oxidation to CO2 was higher in the EDL and plantaris muscles, but similar in the soleus muscle of ad libitum-fed obese rats when compared with lean rats. The magnitude of the difference in isoleucine oxidation was similar when the obese rats were pair fed. No differences in the percentage of plantaris muscle fibers sensitive to alkaline ATPase staining were observed. The plantaris muscle of obese rats, contained a higher proportion of oxidative fibers. These results indicate the great risk in generalizing about metabolic activity of the whole skeletal muscle mass based on observations made on one, or even two, distinct muscles in this animal model. Also, pair feeding of obese to lean Zucker rats did not result in uniform changes in metabolism between muscles of the obese rats.
Animals↗
Induction of ventrolateral hypothalamic fatty acid oxidation in diabetic rats.
Diabetic rats were used to test a previous hypothesis that alterations in ventrolateral hypothalamic (VLH) fatty acid oxidation observed in over- and underfed rats were a function of the animals' peripheral energy balance and not merely a function of their energy intake. Standard adaptations to the diabetic condition were exhibited in streptozotocin diabetic rats such as depressed body weights, hyperphagia and hyperglycemia, elevated serum free fatty acids, depressed insulin concentrations, depressed hepatic glucose oxidation and elevated hepatic fatty acid oxidation. Rates of VLH fatty acid oxidation to CO2 and to an acid, water-soluble fraction in diabetic rats were elevated relative to non-diabetic rats. The alterations in VLH fatty acid oxidation in diabetic rats were similar to changes previously observed in animals exhibiting a negative energy balance. The results were discussed with respect to the concept that VLH fatty acid oxidation was a component in the recognition of peripheral energy balance and, in part, served to alter the regulators of energy balance and food intake.
Animals↗
Uptake and utilization of metabolites in specific brain sites relative to feeding status.
Two experiments were conducted to assess potential alterations in fatty acid and glucose metabolism within specific brain sites in relation to the feeding status of the rat. An in vivo serial analysis of brain palmitate and glucose uptake demonstrated that hypothalamic uptake of these substrates was reciprocally altered with respect to satiety. Hypothalamic uptake of palmitate was increased by 300% and uptake of glucose was decreased by 30% in fasted compared with fed rats. Other regional differences were observed and discussed in the text. An in vitro analysis showed that hypothalamic fatty acid oxidation was affected by feeding status. The ventrolateral hypothalamus (VLH) of fasted rats had 45% greater rates of fatty acid oxidation than VLH of fed rats. No alterations were observed for VLH glucose oxidation and ventromedial hypothalamic glucose and fatty acid oxidation when comparing fed and fasted rats. Other brain sites did not show variance for glucose and fatty acid metabolism relative to feeding status. Fatty acid uptake and subsequent metabolism in the hypothalamus and other brain sites may be one component of food intake control and energy balance regulation.
Animals↗
Exploratory and confirmatory plots of single-channel records.
Graphical displays are used to study open- and closed-time durations of a single ion-channel. CUSUM plots, in conjunction with Kolmogorov-Smirnov type tests, provide checks for changes in channel behaviour. Distributional properties are examined by means of Q-Q and P-P plots. The methods are illustrated using GABA-activated channel records from Ascaris suum.
Animals↗
Effect of maturation on oral breathing in sleeping premature infants.
To evaluate the influence of postnatal maturation on oral breathing, we measured nasal and oral ventilation during sleep and the ventilatory response to nasal occlusion in 11 preterm infants. Studies were repeated at 31-32, 33-34, and 35-36 weeks postconceptional age. Premature infants had rare episodes of spontaneous oronasal breathing during sleep. The frequency of oral breathing in response to nasal occlusion increased with advancing postconceptional age, from 8% +/- 8% at 31-32 weeks to 26% +/- 18% at 33-34 weeks and 28% +/- 33% at 35-36 weeks. Oral breathing in preterm infants, unlike that in term infants, was characterized by intermittent airway obstruction leading to a significant decrease in respiratory rate, tidal volume, minute ventilation, and tcpo2 (P less than 0.005). When inspiratory (Rl) and expiratory (RE) resistances during nasal and oral breathing were compared, Rl increased from 41 +/- 30 to 234 +/- 228 (P less than 0.004) and RE from 62 +/- 16 to 145 +/- 43 cm H2O X L-1 X sec (P less than 0.004). The ability of preterm infants to use the oral route of breathing thus increases with advancing postnatal maturation, but its effectiveness may remain limited by high oral airway resistance.
Female↗