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Biomedical subjects

R J Martin

Publications and source records attributed to R J Martin.

At least 271 records · Page 15Linked to original sources
PubMed1991

A system for automated recording and analysis of feeding behavior.

We have designed and implemented a system that utilizes a network of top-loading balances digitally interfaced to a Macintosh computer. The system simultaneously collects two forms of data which allow the evaluation of the animal's biting and/or licking behavior in addition to cumulative food intake and meal patterns. The system is capable of resuming data acquisition following a power failure without user intervention. Plexiglas cages utilized with the system features adjustable tunnel feeders and are appropriate for use with small rodents. Given appropriate caging, the system may be utilized to evaluate the feeding behavior of other species.

Animals↗
PubMed1991

Effect of low-dose methotrexate on the disposition of glucocorticoids and theophylline.

Low-dose methotrexate (MTX) therapy has been recently proposed as alternative therapy for patients with severe steroid-requiring asthma. Several questions have been raised regarding the mechanism of action, including alteration of pharmacokinetics of two medications used in these patients, specifically, glucocorticoids and theophylline. To address this question, pharmacokinetic studies were performed at baseline and after 6 weeks of treatment with either intramuscular MTX or placebo (folic acid). Plasma concentrations of theophylline were measured by fluorescence polarization immunoassay (TDx, Abbott Diagnostics, Abbott Park, Ill.). Prednisolone, methylprednisolone, and cortisol concentrations were measured by high-performance liquid chromatography. Fifteen adults were enrolled in the double-blind, placebo-controlled trial. No change in prednisolone pharmacokinetic parameters was found. Theophylline clearance decreased an average of 19% in patients randomized to receive MTX, from 48.0 +/- 2.0 ml/hr/kg to 38.9 +/- 3.6 ml/hr/kg (p less than 0.05). This change resembles change observed with theophylline and phenobarbital clearance in which a high degree of interpatient variability is observed. The most likely explanation for the change in theophylline clearance is inhibition of hepatic microsomal enzyme activity. Three patients complained of adverse effects, and dosage was reduced in one patient. The variable effect of MTX on theophylline clearance indicates that theophylline concentration monitoring should be performed in patients receiving both drugs.

Adult↗
PubMed1991

The physiology and pharmacology of neuromuscular transmission in the nematode parasite, Ascaris suum.

The organization of Ascaris motoneurones and nervous system is summarized. There is an anterior nerve ring and associated ganglia, main dorsal and ventral nerve cords which run longitudinally, and a small set of posterior ganglia. Cell bodies of motoneurones are found in the ventral nerve cord and occur in 5 repeating 'segments'; each contains 11 motoneurones. Seven morphological types of excitatory or inhibitory motoneurone are recognized. Each Ascaris somatic muscle cell is composed of the contractile spindle; the bag region, containing the nucleus; the arm; and the syncytial region, the location of neuromuscular junctions. The resting membrane potential of muscle is approximately -30 mV and shows regular depolarizing, Ca-dependent 'spike potentials' superimposed on smaller Na(+)- and Ca2(+)-dependent 'slow waves' and even slower 'modulation waves'. The membrane shows high Cl- permeability. Adjacent cells are electrically coupled so that electrical activity in the cells is synchronized. Acetylcholine (ACh) and gamma-aminobutyric acid (GABA) affect the electrical activity. Bath-applied ACh increases membrane cation conductance, depolarizes the cells, alters the frequency and amplitude of spike potentials and produces contraction. Bath-applied GABA increases Cl- conductance, decreases spike activity and causes hyperpolarization and muscle relaxation. The extra-synaptic ACh receptors on the bag region of Ascaris muscle can be regarded as a separate subtype of nicotinic receptor. ACh and anthelmintic agonists (pyrantel, morantel, levamisole) produce a dose-dependent increase in cation conductance and membrane depolarization which is blocked by tubocurarine, mecamylamine but not by hexamethonium. The potency of GABA agonists, with the exception of sulphonic acid derivatives, correlates with the vertebrate GABAa receptor. The potency of antagonists does not. Thus, bicuculline, securinine, pitrazepine, SR95531 and RU5135 are potent vertebrate GABAa antagonists but have little effect on GABA receptors. The potency order of the arylaminopyridazine GABA antagonists: SR95103, SR95132, SR42666, SR95133, SR95531, SR42627 and SR42640 at the Ascaris GABA receptors contrasts with that at vertebrate GABAa receptors. It has been suggested that the receptor is referred to as a GABAn receptor. Patch-clamp studies show that ACh activates a non-selective cation channel which has a main conductance of 40-50pS and apparent mean open time of 1.3 ms; a smaller channel of 20-30 pS with a similar open-time is also activated. Pyrantel and levamisole also produce openings with similar conductances and open-times.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1991

Plasma histamine, epinephrine, cortisol, and leukocyte beta-adrenergic receptors in nocturnal asthma.

Plasma histamine, cortisol, epinephrine, cyclic adenosine monophosphate (cAMP), and leukocyte beta-adrenergic receptors were measured in asthmatic patients with (n = 7) and without (n = 10) nocturnal asthma at 4 PM and 4 AM and compared with those of normal subjects (n = 10). A twofold higher plasma histamine concentration was observed at 4 AM compared with 4 PM in all groups, with no change in plasma cortisol, epinephrine, and cAMP concentrations. At 4 AM compared with 4 PM, only patients with nocturnal asthma had a significant 33% decrease (p less than 0.05) in mononuclear and polymorphonuclear leukocyte beta-adrenergic receptor density, with no difference in binding affinity in all three groups. Polymorphonuclear leukocytes from patients with nocturnal asthma had significantly impaired response to isoproterenol at 4 AM (17% +/- 7.3% SEM increase in cAMP; p less than 0.05) compared with those of patients without nocturnal asthma (69.4% +/- 13.7%) and normal (80.2% +/- 21.3%) subjects. A significant change in beta-adrenergic receptor density and function occurs at night in patients with nocturnal asthma.

Asthma↗
PubMed1991

Maternal dietary fat type influences the growth and fatty acid composition of newborn and weanling rats.

To determine whether the long-term consumption of different amounts or types of fat by female rats affects the growth and development of their progeny, Wistar rats were fed from weaning either a low fat diet (4.5% by weight) or one of three high fat (32%) diets containing predominantly beef tallow (high saturated fat), corn oil (high polyunsaturated fat) or equal portions of tallow and corn oil (high mixed fat). Offspring were killed at birth or weaning. Weight of newborn pups was lower with maternal consumption of high polyunsaturated fat diets. Carcass composition of newborn pups and body weight of weanling rats was unaffected by maternal diet. The percentage of carcass lipid was greater in weanling rats from all high fat-fed dams. In both newborn pups and weanling rats, percent composition in carcass lipids of 16:0, 16:1 and 18:1 fatty acids generally decreased and 18:2 increased as the high fat maternal diet became more unsaturated. The consumption of diets high in polyunsaturated fatty acids prior to and throughout gestation thus seemed to have a transitory effect on reducing fetal growth in rats.

Animals↗
PubMed1991

A systematic consideration of the neoplastic spectrum of AIDS: registry linkage in Illinois.

To examine unexplored aspects of the association between AIDS and neoplasia, the Illinois AIDS and Cancer Registries were linked. The method integrated use of a personal computer to find exact matches on names and dates of birth with manual review to assure satisfaction of a match definition. Of the factors examined, white race and homosexuality predicted Kaposi's sarcoma (KS) among people with AIDS (PWAs), and white race predicted non-Hodgkin's lymphoma (NHL). Earlier reports of a declining proportion of PWAs with KS were confirmed. Lymphoma (mixed lymphocytic/histiocytic type), while not currently diagnostic of AIDS, occurred more frequently among PWAs than in the Illinois population. For the first time, rates of cancers other than KS and NHL were demonstrated to be significantly increased among PWAs compared with general populations. In the light of these findings, reconsideration of current neoplastic definitions may be useful.

Acquired Immunodeficiency Syndrome↗
PubMed1991

On the sodium and potassium currents of a human neuroblastoma cell line.

1. The patch-clamp method was applied to the study of ionic currents activated by depolarization of undifferentiated IMR-32 human neuroblastoma cells. Whole-cell sodium and potassium currents and single potassium ion channel currents from cell-attached patches were investigated. 2. Cells had a mean resting potential of -38 mV and mean input resistance of 1.6 G omega. Single action potentials were evoked under current clamp during the injection of depolarizing currents. 3. A voltage-dependent inward sodium current was observed which reversed at +44 mV. A Boltzmann fit to the activation curve gave a half-maximal activation voltage of -41.6 mV and a 'slope' of 3.9 mV. The steady-state inactivation curve had a half-maximal inactivation voltage of -81 mV and a 'slope' of 9.7 mV. 4. The time-dependent activation and inactivation of the current displayed classical Hodgkin-Huxley kinetics. Values for the time constants tau m and tau h of 0.16 and 0.63 ms were calculated for a voltage jump from -80 to -10 mV; tau m and tau h decreased as the step potential was changed from -30 to +20 mV. 5. Outward currents were activated in bathing solutions substantially free of anions and could thus be attributed to potassium ions. The tail current reversed in direction on repolarization to -60 mV when the potassium concentration in the bathing solution was increased from 6 to 30 mM. When the bathing solution contained 145 mM-potassium, and the patch pipette, 95 mM, a depolarization to -10 mV from a holding potential of -60 mV evoked an inward current. 6. Outward currents were examined by using voltage pulses which depolarized the cell to -20 mV, or more positive values, from a holding potential of -80 mV and by pulses which depolarized the cell to 0 mV, or to positive values, from a holding potential of -30 mV. A Boltzmann fit of typical activation data gave a half-maximal activation voltage of 17 mV and a 'slope' of 14 mV. 7. The time course of the rising phase of the current was described by a function of the form A(1-exp[-(t-delta t)/tau]), where delta t varied between 1 and 4 ms and tau varied between 4 and 27 ms, decreasing with increasing depolarization. There was no evidence for a fast transient component. 8. The amplitude of outward currents was reduced by extracellular calcium ions, cobalt ions, tetraethylammonium and 4-aminopyridine.(ABSTRACT TRUNCATED AT 400 WORDS)

Biological Transport, Active↗
PubMed1991

Influence of fatty acid oxidation in lateral hypothalamus on food intake and body composition.

This study tested the concept that the level of fatty acid oxidation in the ventrolateral hypothalamus (VLH) reflects peripheral energy stores and elicits compensatory responses to changes in energy balance status. Fatty acid oxidation rates in the VLH were chronically altered over a 14-day period by infusing into the VLH either 0.1 mM 4-pentenoic acid (4-PA; 5 ng/h) or 1.0 mM L-carnitine (L-Carn; 98 ng/h). Fatty acid oxidation rates in the VLH were altered to a similar extent as by overfeeding (reduced 37% by 4-PA) and dietary restriction (increased 28% by L-Carn). Diffusion of infusates was limited, since there were normal rates of fatty acid oxidation in the ventromedial hypothalamus and cortex. There were no significant effects of altering fatty acid oxidation in the VLH on food intake, body weight, body composition, or serum levels of glucose, insulin, and free fatty acids. The results of this experiment indicate that the level of fatty acid oxidation in the VLH is unlikely to independently elicit changes in food intake or peripheral metabolism.

Animals↗
PubMed1991

Maturation of respiratory reflex responses in the piglet.

Stimulation of chemo-, irritant, and pulmonary C-fiber receptors reflexly constricts airway smooth muscle and alters ventilation in mature animals. These reflex responses of airway smooth muscle have, however, not been clearly characterized during early development. In this study we compared the maturation of reflex pathways regulating airway smooth muscle tone and ventilation in anesthetized, paralyzed, and artificially ventilated 2- to 3- and 10-wk-old piglets. Tracheal smooth muscle tension was measured from an open tracheal segment by use of a force transducer, and phrenic nerve activity was measured from a proximal cut end of the phrenic nerve. Inhalation of 7% CO2 caused a transient increase in tracheal tension in both age groups, whereas hypoxia caused no airway smooth muscle response in either group. The phrenic responses to 7% CO2 and 12% O2 were comparable in both age groups. Lung deflation and capsaicin (20 micrograms/kg iv) administration did not alter tracheal tension in the younger piglets but caused tracheal tension to increase by 87 +/- 28 and 31 +/- 10%, respectively, in the older animals (both P less than 0.05). In contrast, phrenic response to both stimuli was comparable between ages: deflation increased phrenic activity while capsaicin induced neural apnea. Laryngeal stimulation did not increase tracheal tension but induced neural apnea in both age groups. These data demonstrate that between 2 and 10 wk of life, piglets exhibit developmental changes in the reflex responses of airway smooth muscle situated in the larger airways in response to irritant and C-fiber but not chemoreceptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effects of CO2 rebreathing on pulmonary mechanics in premature infants.

The effects of hypercapnia produced by CO2 rebreathing on total pulmonary, supraglottic, and lower airway (larynx and lungs) resistance were determined in eight premature infants [gestational age at birth 32 +/- 3 (SE) wk, weight at study 1,950 +/- 150 g]. Nasal airflow was measured with a mask pneumotachograph, and pressures in the esophagus and oropharynx were measured with a fluid-filled or 5-Fr Millar pressure catheter. Trials of hyperoxic (40% inspired O2 fraction) CO2 rebreathing were performed during quiet sleep. Total pulmonary resistance decreased progressively as end-tidal PCO2 (PETCO2) increased from 63 +/- 23 to 23 +/- 15 cmH2O.l-1.s in inspiration and from 115 +/- 82 to 42 +/- 27 cmH2O.l-1.s in expiration between room air (PETCO2 37 Torr) and PETCO2 of 55 Torr (P less than 0.05). Lower airway resistance (larynx and lungs) also decreased from 52 +/- 22 to 18 +/- 14 cmH2O.l-1.s in inspiration and from 88 +/- 45 to 30 +/- 22 cmH2O.l-1.s in expiration between PETCO2 of 37 and 55 Torr, respectively (P less than 0.05). Resistance of the supraglottic airway also decreased during inspiration from 7.2 +/- 2.5 to 3.6 +/- 2.5 cmH2O.l-1.s and in expiration from 7.6 +/- 3.3 to 5.3 +/- 4.7 cmH2O.l-1.s at PETCO2 of 37 and 55 Torr (P less than 0.05). The decrease in resistance that occurs within the airway in response to inhaled CO2 may permit greater airflow at any level of respiratory drive, thereby improving the infant's response to CO2.

Airway Resistance↗
PubMed1991

Effect of excess dietary fat during the third trimester of pregnancy on maternal, placental, and fetal metabolism in the pig.

The effect of excessive intake of dietary fat during late gestation on maternal, placental, and fetal metabolism was studied. Twelve pregnant gilts were fed ad libitum diets containing 4 (control) or 55% (added fat) calories as fat, beginning on day 70 of gestation. On day 110, glucose and palmitate oxidation, and incorporation into fatty acids by maternal adipose tissue, maternal and fetal placenta, and fetal liver and adipose tissue were determined. Caloric efficiency and adipose tissue glucose utilization were reduced in the added fat gilts, while placenta metabolism at high media palmitate concentrations was increased. Fetal development and metabolism were for the most part unaffected by maternal diet; thus, the fetus appears to be protected from dietary excess through adaptations of both maternal and placental metabolism.

Adipose Tissue↗
PubMed1991

Airways inflammation in nocturnal asthma.

Nocturnal asthma is a frequent problem, but the mechanism is unclear. We investigated the possibility that airways inflammation occurred during the night. Bronchoalveolar lavage fluid was analyzed in asthmatic patients with (n = 7) and without nocturnal asthma (n = 7) at 1600 and 0400 h. The nocturnal asthma group had an increase in the total leukocyte count (24.0 +/- 7.0 to 41.1 +/- 9.9 x 10(4) cells/ml, p less than 0.05), neutrophils (1.1 +/- 0.6 to 3.7 +/- 1.5 x 10(4) cells/ml, p less than 0.05), and eosinophils (0.5 +/- 0.1 to 1.7 +/- 0.7 x 10(4) cells/ml, p less than 0.05) from 1600 to 0400 h. Cellular components for the non-nocturnal asthma group did not change. Between groups, the 1600-h cells were similar. At 0400 h the nocturnal asthma group had significantly higher total leukocyte, neutrophil, eosinophil, lymphocyte, and epithelial cell counts. For all subjects, the overnight fall in peak expiratory flow rates was correlated to the change in neutrophils (r = 0.54, p less than 0.05) and eosinophils (r = 0.77, p less than 0.05). We conclude that the nocturnal worsening of asthma has an associated cellular inflammatory response that is not seen in patients without overnight decrements in lung function. This inflammatory response together with epithelial damage may be important factors in the etiology of nocturnal asthma.

Asthma↗
PubMed1991

Antagonist properties of arylaminopyridazine GABA derivatives at the Ascaris muscle GABA receptor.

1. In a previous study, it was shown that the potency order for two arylamino-pyridazine derivatives, SR95531 and SR95103, was different in Ascaris suum when compared to vertebrate preparations. SR95531, the most potent analogue at the vertebrate GABAA receptor, was found to be very weak at antagonizing GABA responses in Ascaris, but SR95103, approximately 20 times less potent than SR95531 in vertebrate preparations, was more potent than SR95531 in Ascaris. These results suggested the existence of different accessory binding sites at the Ascaris GABA receptor. 2. To test this hypothesis, the effects of a series of arylaminopyridazine derivatives of GABA on the GABA response in Ascaris suum muscle were investigated using a two-microelectrode current-clamp technique. 3. The results showed that SR42627, a potent antagonist at the GABAA receptor, was one of the weakest analogues in Ascaris muscle. In contrast, SR95132, virtually inactive in vertebrate preparations, was equipotent to SR95103, the most potent analogue of the series in Ascaris muscle. 4. The three most potent analogues in Ascaris, SR95103, SR95132 and SR42666, displace GABA dose-response curves to the right without decreasing the maximal response. The modified Schild plots for these compounds are consistent with a competitive mechanism involving two molecules of GABA and only one molecule of antagonist interacting with the receptor. The estimated dissociation constants for SR95103, SR95132 and SR42666 are, respectively, 64, 65 and 105 mumol l-1. 5. Structure-activity relationships for this series of compounds were examined in Ascaris and compared to those in vertebrates. Substitution on the pyridazine ring in the 4-position, while detrimental for the antagonist potency at the vertebrate GABAA receptor, appears to be a prerequisite for antagonistic activity on the Ascaris muscle GABA receptor. These results are interpreted in terms of the accessory binding site theory of Ariëns, and suggest the existence of different accessory binding sites on the Ascaris GABA receptor.

Animals↗
PubMed1991

Nasal CPAP in nonapneic nocturnal asthma.

Nasal CPAP has been shown to improve nocturnal asthma in those patients with associated sleep apnea. We studied seven nonapneic, nonsnoring asthmatics to determine the effect of CPAP in this patient population. On the CPAP night vs the baseline night, there was a significant worsening of sleep architecture. This included increased awake time and decreased REM sleep. For the group, the overnight decrement in FEV1 was not improved. Of interest, two patients did have a marked improvement in FEV1 associated with improved oxygen saturation on the CPAP night. These individuals were restudied only on supplemental oxygen. This intervention also improved the overnight FEV1 and allowed the patients to have better sleep compared to the CPAP night. We concluded that CPAP is associated with disrupted sleep architecture in nonapneic asthmatics and nocturnal oxygen desaturation may play a role in the development of nocturnal asthma.

Adult↗
PubMed1991

Growth hormone secretion in the obese male rat: modulation by the gonadal and thyroid axes.

The present study was designed to determine if either the testes or thyroid plays a role in the blunted GH secretion observed in the obese male rat. Analysis of individual GH secretory profiles in adult lean and obese Zucker rats revealed a severe attenuation of both mean GH levels and individual GH pulse amplitudes in obese rats as well as a significant lowering of circulating testosterone levels. Normalization of the testosterone levels by the use of sc Silastic capsules elevated but did not normalize GH pulse amplitudes in obese animals. Further, the GH response to either rat GH-releasing factor (5 mu/kg) or morphine (1 mg/kg) were reduced in obese male rats. In contrast, the thyroid axis showed minimal change in obese animals. A slight reduction in free T3 levels in serum was observed while free and total T4 and total T3 were normal in obese rats. Further, mean circulating TSH levels and the TSH response to 500 ng/kg TRH were not altered in fat rats. Thus, the reduced GH secretion observed in the obese rat is not paramount to an alteration in either gonadal or thyroid function. This alteration of the GH secretory axis may not be attributable to one factor but more likely caused by a number of concomitant deficits which may act in concert to manifest impaired GH secretion.

Animals↗