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Biomedical subjects

R J Martin

Publications and source records attributed to R J Martin.

At least 217 records · Page 12Linked to original sources
PubMed1994

Type II corticosteroid receptor stimulation increases NPY gene expression in basomedial hypothalamus of rats.

Evidence has suggested that glucocorticoids may increase neuropeptide Y (NPY) activity and gene expression. In the present study, we sought to determine the corticosteroid receptor subtype through which glucocorticoids increase NPY gene expression in the basomedial hypothalamus. This was accomplished by continuous administration of selective type I and II corticosteroid agonists in adrenalectomized Sprague-Dawley rats. Dot-blot analysis was performed, and the amount of NPY mRNA was determined. Additionally, serum insulin and glucose concentrations were determined. Type II receptor stimulation increased NPY mRNA levels in the basomedial hypothalamus above that of sham animals. This implies that type II receptor stimulation by high physiological concentrations of serum corticosterone may also increase NPY gene expression in the basomedial hypothalamus. The type II receptor agonist-induced increase in NPY gene expression did not appear to be mediated by a decrease in serum insulin concentrations. The present results may have relevance to the increased gene expression of NPY observed in the basomedial hypothalamus of obese Zucker rats and in food-deprived animals.

Adrenalectomy↗
PubMed1994

Central chemosensitivity affects respiratory muscle responses to laryngeal stimulation in the piglet.

Stimulation of laryngeal afferent fibers triggers reflex apnea, which can be very long in the neonatal period. The purpose of this study was twofold: 1) to determine the effect of superior laryngeal nerve (SLN) stimulation on expiratory as well as inspiratory muscle activity and 2) to compare the respiratory response to SLN stimulation under conditions that would appear to alter the level of central chemosensitivity in anesthetized spontaneously breathing piglets. In protocol 1, we measured electromyogram (EMG) responses from the diaphragm (DIA), triangularis sterni, and transversus abdominis muscles to graded SLN stimulation; in protocol 2, we compared the DIA response to different levels of SLN stimulation during normocapnia, hypercapnia, and cooling of the ventrolateral medullary surface (VMS). SLN stimulation performed during normocapnia caused significantly greater inhibition of both expiratory muscles (triangularis sterni and transversus abdominis) than of the DIA. During hypercapnia, laryngeal stimulation-induced inhibition of all three muscles was significantly diminished, and the degree of inhibition for the three muscles became equivalent. Inhibition of the DIA EMG was significantly greater with SLN stimulation during VMS cooling than with a VMS temperature of 38 degrees C. We conclude that the magnitude of respiratory inhibition induced by laryngeal stimulation during early postnatal life is inversely related to the level of central chemical input and speculate that functional deficiency of structures located in the VMS may contribute to potentially life-threatening apnea in infants.

Animals↗
PubMed1994

Responses of lung parenchyma and airways to tachykinin peptides in piglets.

The tachykinin peptides substance P (SP) and neurokinin A (NKA) have been shown to induce tracheal smooth muscle contraction in piglets, and the enzyme neutral endopeptidase has been shown to modulate this effect. In these studies, we compared the SP and NKA responsiveness of piglet airways and lung parenchymal tissues in anesthetized paralyzed open-chest piglets 2-3 wk old, partitioning total lung resistance (RL) into airway resistance (Raw) and tissue resistance (Rti). During tidal breathing, pressure was measured at the trachea and in two alveolar regions by means of alveolar capsules. Intravenous administration of SP caused concentration-dependent increases in Rti and Raw and a decrease in dynamic lung compliance. Under baseline conditions, Rti contributed 74.6 +/- 1.9% (SE) of RL, and at any level of constriction, Rti accounted for > 50% of RL. The responses of Rti and Raw to NKA were negligible and were always significantly weaker than those to SP. These results indicate that both central airways and tissue contractile elements respond vigorously to SP, but not to NKA, in maturing piglets.

Airway Resistance↗
PubMed1994

Blood and bronchoalveolar lavage endothelin-1 levels in nocturnal asthma.

Endothelin-1 (ET-1) is a potent endogenous vasoconstrictor that was recently shown to exhibit bronchoconstrictive properties in vitro. In asthmatic patients, the expression of ET-1 peptide was also shown to be increased in endobronchial biopsies. Thus, we postulated that ET-1 could be higher in subjects with nocturnal asthma. Bronchoalveolar lavage (BAL) fluid levels of ET-1 were measured in 10 subjects with nocturnal asthma and 6 normal volunteers at 0400 h (nighttime groups) and in an additional 7 subjects with nocturnal asthma and 6 control subjects at 1600 h (daytime groups). ET-1 levels were significantly lower in the nighttime asthmatic group (median 39.3 pg/mg protein, 7.3 to 44.0 IQ) than in the nighttime control group (median 77.4 pg/mg protein, 46.8 to 121.9 IQ; p = 0.01) or the daytime asthmatic group (median 56.8 pg/mg protein, 51.6 to 97.4 IQ; p = 0.04). ET-1 levels did not differ significantly between the daytime asthmatic and the daytime control groups or between control groups. Additionally, the overnight reduction in lung function was significantly correlated with lower BAL ET-1 levels (r = 0.57, p = 0.05). These results suggest that ET-1 plays a role in the overnight worsening of asthma and perhaps is more tightly tissue bound, resulting in lower levels of BAL fluid.

Adult↗
PubMed1994

Dilatation of bronchial stenoses due to sarcoidosis using a flexible fiberoptic bronchoscope.

Stenosis of the trachea and bronchi can complicate many diseases and lead to significant pulmonary complaints. Unfortunately, steroids rarely yield satisfactory results in reversing symptoms. We describe six patients with symptomatic airway stenosis from sarcoidosis, all of whom were refractory to steroid therapy. By using a Fogarty embolectomy catheter inserted through the inner channel of a flexible bronchoscope, we were able to dilate the stenotic areas under direct vision. Patients had significant subjective improvement following dilatation and no significant complications occurred. We believe this technique represents an improvement on previously described methods because it can easily access the upper lobes and more distal segments and can be performed at the bedside.

Adult↗
PubMed1994

Management of patients with chronic asthma: controversies and future directions.

Hospitalizations and mortality due to asthma have increased, despite advances in asthma treatment. Several aspects of the management of patients with chronic asthma are under discussion in efforts to address this problem. Therapeutic interventions, including the use of theophylline, corticosteroids, and beta 2-agonist chronotherapy, will be reviewed, with the goal of defining ways of attaining the optimal response when using pharmacologic and nonpharmacologic regimens in the treatment of patients with chronic asthma.

Asthma↗
PubMed1993

The influence of human growth hormone (GH) and thyroxine (T4) on the differentiation of adipose tissue in the fetus.

Late term fetuses from genetically obese dams have slightly larger fat cells, greater adipose tissue lipoprotein lipase (LPL) activities, elevated levels of thyroid hormones, and depressed growth hormone (GH) levels when compared to fetuses from lean dams. We have investigated the influence of thyroid hormone and GH status per se on these and other adipose tissue traits by chronically treating hypophysectomized (hypox) fetuses (day 70) between day 90 and 105 of gestation with either thyroxine (T4) or human GH. Treatment with T4 decreased body weights (P<.05), increased serum T4 levels (P<.05), and enhanced skin and hair development (P<.05). Quantitative analysis of sections of perirenal and subcutaneous adipose tissue indicated that T4 increased LPL activity (P<.05), slightly increased fat cell size, and more than doubled (P<.05) lipid accretion. A hypox induced deficit in fat cell cluster number in the outer layer of subcutaneous tissue was normalized by T4 (P<.05). Conversely, human GH (hGH) treatment had no influence on body weight, increased serum hGH levels, decreased fat cell size (P<.05) and LPL activity (P<.05) but had no influence on lipid accretion. Quantitative analysis of adipose tissue sections provided direct and indirect evidence of a "critical" or "sensitive" period between 90 and 105 days, since fetal hypox at day 70 severely impeded preadipocyte recruitment/replication during this period. Furthermore, T4 but not GH effectively normalized this hypox-induced deficiency in preadipocyte development. Therefore, T4 may have a major role in preadipocyte recruitment/replication during late fetal life.

Adipocytes↗
PubMed1993

A patch-clamp study of the ionic selectivity of the large conductance, Ca-activated chloride channel in muscle vesicles prepared from Ascaris suum.

Plasma membrane vesicles prepared from the bag region of the somatic muscle cell of the parasite Ascaris suum contain a large conductance, voltage-sensitive, calcium-activated chloride channel. The ability of this channel to conduct a variety of anions has been investigated using the patch-clamp technique on isolated inside-out patches of muscle membrane. Symmetrical Cl solutions (140 mM) produced single-channel I/V plots with reversal potentials of 0 mV, substitution of bath Cl by 140 mM NO3, Br and I caused depolarizing shifts in the reversal potentials. Replacement of the internal Cl by F (140 mM) caused a large hyperpolarizing shift in the reversal potential. The channel displayed a permeability sequence of I > Br = NO3 > Cl > F which differed from the corresponding conductance sequence Cl > NO3 = Br = I > F. The ionic environment within the channel pore has been investigated using Reuter and Stevens (1980) plots to describe the selectivity and "fluidity" of the channel pore. In addition, the approach of Wright and Diamond (1977) was employed to estimate the number of cationic binding sites within the channel pore. The channel is relatively fluid but the number of cationic binding sites varies inversely with the ionic radius of the anion from 2.15 for F to 0.89 for the large planar anion NO3.

Animals↗
PubMed1993

Affinity of hepatic glucocorticoid receptors is influenced by energy/feeding status.

Genetically obese animals have been shown to have a reduced number and affinity of glucocorticoid receptors. The relationship between the alterations in receptor binding and the regulation of energy balance is not known. We sought to determine the role of body energy/feeding status on the binding characteristics of glucocorticoid receptors. To accomplish this, we examined the effect of long-term food restriction on the number and affinity of hepatic glucocorticoid receptors from Sprague-Dawley rats. After 3 weeks of food restriction (40% of ad lib), animals were bilaterally adrenalectomized. Livers were removed, a crude cytosolic glucocorticoid receptor fraction was isolated, and radioreceptor assays were performed. Glucocorticoid receptors from food-restricted rats showed a significant reduction in the dissociation constant (Kd) as compared to receptors derived from free-feeding controls. No difference in receptor number was observed. These results suggest that energy or feeding status of the animal may influence the affinity of hepatic glucocorticoid receptors, while receptor number may be independent of this status.

Adrenalectomy↗
PubMed1993

Pharyngeal dilator muscle contractile and endurance properties in neonatal piglets.

Pharyngeal dilator muscles are critical for maintaining upper airway patency in the neonatal period. The present study examined in vitro the contractile properties of a pharyngeal dilator muscle, the sternohyoid, in 1-7-day-old piglets (n = 24). Isometric contraction and half-relaxation times were 36.7 +/- 1.1 and 30.9 +/- 1.2 msec, respectively. Twitch potentiation ('staircase phenomenon') and post-tetanic potentiation were noted following repetitive stimulation. During prolonged repetitive stimulation with a standard (40 Hz) fatigue test, muscle force declined gradually over time, with loss of half of the initial force occurring over 138 +/- 11 sec, and a 2-min fatigue index (ratio of force at 2 min to initial force) of 0.52 +/- 0.03. An additional 10 piglets were studied at ages of 14-20 days. Muscle from older piglets had comparable isometric twitch kinetics as that of younger animals. However, sternohyoid muscle from the older piglets had worse endurance than muscle from the younger animals, as indicated by a shorter time required for force to decrease by half (86 +/- 10 sec, P < 0.01) and a lower 2-min fatigue index (0.36 +/- 0.03, P < 0.01). These data indicate that for the sternohyoid muscle of the newborn piglet (a) physiological properties are consistent with moderate to fast contraction with good endurance, (b) force potentiates during repetitive twitch stimulation and following a brief period of tetanic stimulation, and (c) there is worsening of endurance but no change in isometric twitch kinetics with increasing age during the first weeks of life.

Aging↗
PubMed1993

Neuromuscular transmission in nematode parasites and antinematodal drug action.

Some anthelmintic drugs interfere selectively with nematode neuromuscular transmission. These drugs include: the nicotinic agonists, e.g. levamisole, the gamma-amino butyric acid agonist piperazine, and the avermectins which open Cl- channels. The physiology and pharmacology of neuromuscular transmission in nematodes is reviewed and the actions of antinematodal drugs which interfere with the transmission described. The results of experiments on the large porcine-intestinal nematode parasite, Ascaris suum, form the basis of the account presented but experiments on other nematodes suggest that these observations may be generalized. Results of some experiments on the small free living nematode Caenorhabditis elegans are also included.

Acetylcholine↗
PubMed1993

Patch-clamp and chloride channels in Ascaris suum.

Single-channel electrophysiology is an invaluable tool fo the study of ion channels. However, it is a technique that has failed to attract widespread use by parasitologists. Here, Diane Dixon and Richard Martin outline the principles undelrying single channel recording and highlight its uses in the discovery of a new and unusual chloride channel in the musculature of Ascaris suum.

Journal Article↗
PubMed1993

Increased respiratory drive as an inhibitor of oral feeding of preterm infants.

This study was designed to determine whether increased respiratory drive induced by inhalation of carbon dioxide would alter the reflex and voluntary components of feeding. For 10 preterm infants (mean +/- SD: postconceptional age at study, 34 +/- 2 weeks; weight, 2.1 +/- 0.2 kg), four trials of nutritive feeding were offered: two while the infants were inhaling a gas mixture containing 40% oxygen and two while the infants were breathing 40% oxygen and 7% carbon dioxide. Nasal airflow was monitored with a pneumotachygraph. Pressure-sensitive catheters in the esophagus and in the feeding nipple were used to detect swallowing and sucking. Sucking frequency and pattern, rate of swallowing, end-tidal carbon dioxide, and minute ventilation were recorded for 30-second epochs during feeding. When the inhaled gas mixture was switched from 40% oxygen to 40% oxygen and 7% carbon dioxide, sucking frequency decreased from 53 +/- 10 to 48 +/- 12 and from 54 +/- 12 to 40 +/- 19 sucks/min, respectively (p < 0.005). Frequency of swallowing also fell during the two feeding epochs on 7% carbon dioxide, from 45 +/- 15 to 40 +/- 15 and from 43 +/- 14 to 31 +/- 16 swallows/min (p < 0.003). Thus acute hypercapnea was accompanied by a decrease in rate of both sucking and swallowing during nutritive feeding. Increased ventilatory drive may directly inhibit nutritive feeding behavior in premature infants.

Bottle Feeding↗
PubMed1993

Influence of the pituitary on lipolysis and lipogenesis in fetal pig adipose tissue.

This study was performed to verify and further characterize the role of neuroendocrine factors in the regulation of fetal adipose metabolism. On day 72 to 74 of gestation, pig fetuses in one uterine horn were hypophysectomized (hypoxed) by micro-cauterization, fetuses in the other horn served as sham controls. Fetuses were removed by laparotomy on day 110 of gestation. Slices of subcutaneous adipose tissue from control fetuses responded to lipolytic stimulation by norepinephrine alone (NE; 1 microgram/ml), NE plus adenosine deaminase (160 mUnits/ml) or dibutyryl cyclic AMP (5 mM). Adipose tissue from hypoxed fetuses, however, responded to lipolytic stimulation by only dibutyryl cyclic AMP, not NE. Lipogenesis in adipose tissue slices, as quantitated by 3H2O incorporation into triglyceride fatty acids, was increased 2.6 fold by hypophysectomy. These results demonstrate the necessity of a functioning pituitary in the normal regulation of fatty acid synthesis and receptor-mediated lipolytic response in developing fetal adipose tissue.

Adenosine Deaminase↗
PubMed1993

Activity of the hypothalamic-pituitary-adrenal axis is elevated in rats with activity-based anorexia.

Activity-based anorexia is characterized by suppressed food intake and excessive physical activity. These behaviors are typical of persons with anorexia nervosa. Activity of the hypothalamic-pituitary-adrenal axis is known to be elevated in anorexia nervosa. We investigated the status of this axis in activity-based anorexia. Meal fed-control (MFC) and meal fed-wheel running (MFWR) rats were given access to food for 90 min daily; MFWR animals were allowed access to an activity wheel the remainder of the day. The experiment terminated when MFWR animals reached 75% of preexperimental body weight (males 3.9 +/- 0.3 d; females 4.2 +/- 0.2 d). Male and female MFWR rats consumed less food than MFC animals, while maintaining a high level of wheel running. Corticosterone concentrations were significantly elevated in MFWR animals. Corticotropin-releasing hormone mRNA concentrations in the paraventricular nucleus were not different. Relative adrenal gland weights were greater and thymus gland weights were lower in MFWR animals. Changes in food intake could not be explained by differences in insulin, glucose, beta-hydroxybutyrate or norepinephrine concentrations. Our results suggest increased activity of the hypothalamic-pituitary-adrenal axis in activity-based anorexia.

Animals↗
PubMed1993

Levamisole-activated single-channel currents from muscle of the nematode parasite Ascaris suum.

1. The patch-clamp technique was used to examine levamisole-activated channels in muscle vesicles from Ascaris suum. Cell-attached and isolated inside-out patches were used. 2. Levamisole (1-90 microM), applied to the extracellular surface, activated channels which had apparent mean open-times in the range 0.80-2.85 ms and linear I/V relationships with conductances in the range 19-46 pS. Ion-replacement experiments showed the channels to be cation selective. 3. The kinetics of the channels were analysed. Generally open- and closed-time distributions were best fitted by two, and three exponentials respectively, indicating the presence of at least two open states and at least three closed states. The distributions of burst-times were best-fitted by two exponentials. 4. Channel open- and burst-times were voltage-sensitive: at low levamisole concentrations (1-10 microM), they increased with hyperpolarization. At higher concentrations of levamisole (30 microM and 90 microM) flickering channel-block was observed at hyperpolarized potentials. Using a simple channel-block model, values for the blocking dissociation constant, KB were determined as 123 microM at -50 mV, 46 microM at -75 mV and 9.4 microM at -100 mV. 5. At the higher concentration of levamisole (30 microM and 90 microM) long closed-times separating 'clusters' of bursts were observed, at both hyperpolarized and depolarized membrane potentials and this was interpreted as desensitization.

Animals↗
PubMed1993

Development of cholinergic innervation and muscarinic receptor subtypes in piglet trachea.

We studied physiological and pharmacological maturation of cholinergic innervation to tracheal smooth muscle in piglets at three ages: < 7 days, 2-3 wk, and 10 wk. Change in tracheal tension was measured in vivo from a tracheal segment and normalized for its size. Electrical vagal stimulation induced a significantly weaker increase in tracheal tension at < 7 days when compared with 2-3 and 10 wk. In vivo studies employing vagal stimulation before and after topical application of pirenzepine (an M1 muscarinic receptor blocker) and in vitro pharmacological studies evaluating the inhibition of [3H]quinuclidinyl benzilate (QNB) binding by pirenzepine demonstrated that immature M1-receptor function could not account for the weak tracheal smooth muscle responses in the first week. Topical application of the cholinergic agonist methacholine to the tracheal segment also induced a significantly weaker contractile response at < 7 days when compared with 2-3 and 10 wk. Total density of muscarinic receptors, as well as the M1 and M3 muscarinic subtypes, was not statistically different among < 7-day-old, 1- to 3-wk-old, and adult animals. Receptor binding studies in 1-3 wk and adult animals demonstrated biphasic dose-dependent inhibition of [3H]QNB binding in tracheal smooth muscle membranes by methacholine, with a high-affinity component dependent on the availability of G protein. These high-affinity muscarinic receptors coupled to G protein were absent in < 7-day-old piglets. We speculate that the weak tracheal smooth muscle contraction observed during the first week of life is in part secondary to immature G protein function.

Administration, Topical↗