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Biomedical subjects

R J Martin

Publications and source records attributed to R J Martin.

At least 235 records · Page 13Linked to original sources
PubMed1993

Regulation of expiratory muscles during postnatal development in anesthetized piglets.

We compared maturation of the responses of the rib cage [triangularis sterni (TS)] and abdominal [transversus abdominis (TA)] expiratory muscles with each other and with the responses of the diaphragm (DIA) during hypercarbic and hypoxic stimulation. Studies were performed in anesthetized (urethan and chloralose) piglets of two age groups (< 6 days, n = 10; 14-21 days, n = 11) before and after bilateral cervical vagotomy. Hypercarbia (7% CO2-93% O2) was associated with comparable sustained increases in the minute electromyograms (EMGs) of both TS and TA, which were closely coupled to the DIA responses in both age groups. Hypoxia (12% O2-88% N2) caused a biphasic response of the minute EMG of both expiratory muscles and DIA; these biphasic responses were less prominent at 14-21 days than at < 6 days. Vagotomy caused an increase in the amplitude of both TS and TA (38 +/- 30 and 27 +/- 21%, respectively) as well as the DIA (45 +/- 16%) but did not affect their relative responses to chemostimulation. We conclude that during postnatal development 1) the rib cage and abdominal expiratory muscle responses to chemostimulation are coupled to each other and parallel those of the DIA and 2) the presence of vagal afferents attenuates the drive to both inspiratory and expiratory motoneurons under the current experimental conditions but does not influence the relative responses of expiratory muscles and DIA to hypercarbia or hypoxia. We speculate that comparable activation of inspiratory and expiratory pumping muscles serves to stabilize respiratory control in the face of altered chemosensory or vagal inputs during early postnatal life.

Afferent Pathways↗
PubMed1993

Effect of lung volume maintenance during sleep in nocturnal asthma.

Previous studies have shown that lung volume decreases and airway resistance increases during sleep in patients with nocturnal asthma. To determine whether the fall in lung volume per se causes the overnight decrement in forced expiratory volume in 1 s (FEV1) and/or increase in bronchial responsiveness, we investigated the effect of preventing this nocturnal decrease in lung volume. The mean volume change on a baseline night was -16.3 +/- 1.6% from presleep values and on the volume maintenance night +7.1 +/- 3.0% (P = 0.0001). However, this maintenance of lung volume did not alter the overnight decrement in FEV1 (-29.6 +/- 5.2% baseline vs. -30.2 +/- 5.8% volume maintenance). Similarly, the increase in bronchial responsiveness was also unaltered from baseline to volume maintenance nights, with presleep provocative concentrations of methacholine producing a 20% decrement in FEV1 of 0.28 +/- 0.15 vs. 0.22 +/- 0.7 mg/ml, respectively, and postsleep values of 0.07 +/- 0.03 vs. 0.04 +/- 0.02 mg/ml, respectively. Thus the fall in lung volume during sleep in the nocturnal asthmatic patient is a result, not a cause, of the overnight worsening of lung function.

Adult↗
PubMed1993

Endocrine regulation of fetal adipose tissue metabolism in the pig: role of thyroxine.

This study was performed to characterize the role of thyroxine (T4) in the regulation of fetal adipose tissue metabolism. On day 70 of gestation, pig fetuses were hypophysectomized (hypoxed) by microcauterization. Both hypoxed and intact fetuses were implanted subcutaneously with T4 pellets or received no hormone replacement. Fetuses were removed by laparotomy on day 90 of gestation. Additional fetuses were hypoxed on day 70, implanted with T4 pellets on day 90 and removed on day 105 of gestation. Serum T4 levels were similar in hypox + T4 and intact + T4 fetuses and increased in both groups relative to their respective controls. T4 supplementation restored the lipolytic response to isoproterenol and enhanced the response to dibutyryl cyclic AMP at 90 days in hypoxed animals but had no effect on basal or stimulated lipolysis in intact fetuses. T4 induced a dramatic increase in lipogenesis in hypoxed fetuses when administered during either fetal period and produced a slight though significant increase in basal lipogenesis in intact fetuses when administered from days 70 to 90 of gestation. However, T4 had no effect on basal or insulin-stimulated lipogenesis in intact fetuses when administered from days 90 to 105 of gestation. These results indicate that T4 may have a primary influence on fetal adipose tissue metabolism only in the absence of inhibition from counterregulatory hormones of pituitary origin.

Adipose Tissue↗
PubMed1993

Nocturnal asthma: circadian rhythms and therapeutic interventions.

The pathophysiology of nocturnal asthma is closely associated with chronobiology, the science of biologic processes that have time-related rhythms. The 24-h cycle (circadian rhythm) is especially important in understanding the changes in pulmonary function that occur in sleeping asthmatics. Nocturnal asthma can be seen as representing an exaggerated amplitude of normal circadian patterns, including increased airway responsiveness and decreased lung function at night and in the early morning. Circadian changes in epinephrine, AMP, histamine and other inflammatory mediators, cortisol, vagal tone, body temperature, and lower airway secretions are potential mechanisms that favor nocturnal bronchoconstriction. Circadian variation in pulmonary function, as well as the effect of therapeutic interventions, can be readily demonstrated by having patients record peak expiratory flow rate values at different times of the day and night, using a peak flow meter. The treatment of nocturnal asthma requires a chronopharmacologic approach, in which more intense therapy is targeted to coincide with the time that the disease is the worst. Chronopharmacology includes the strategic use of longer-acting beta-agonists, theophylline, corticosteroids, and anticholinergics. Understanding the kinetics of the different drug preparations is necessary for most effective timing of dose. Future treatment of nocturnal asthma will continue to be guided by increased understanding of circadian and sleep-related events.

Asthma↗
PubMed1993

The effects of inhaled interferon gamma in normal human airways.

Recent studies suggest that cytokines such as recombinant interferon-gamma (rIFN-gamma) may play a role in the treatment of certain respiratory conditions associated with infection and inflammation. This study was designed to determine if rIFN-gamma could be delivered effectively in a group of normal human volunteers. The effectiveness of the inhaled delivery system was demonstrated by the recovery of free IFN-gamma in bronchoalveolar lavage (BAL) fluid and macrophage (M phi) expression of IP-10, an IFN-gamma-inducible molecule, after therapy but not at baseline. IL-1 beta, but not IL-8, gene transcripts also showed evidence for up-regulation after rIFN-gamma therapy. Compared with baseline, inhaled rIFN-gamma did not significantly alter clinical symptom scores, spirometry, morning peak expiratory flow rate (PEFR), or the response to methacholine. Of interest, the evening PEFR increased significantly (p = 0.02), from 568 +/- 36 L/min at baseline to 584 +/- 33 L/min after inhaled rIFN-gamma. Although there was no significant change in total white cell count in BAL fluid, the cellular composition did demonstrate a significant decrease in percentage of alveolar M phi (p = 0.02) and an increase in percentage of lymphocytes (p = 0.02) after rIFN-gamma. There were no histologic differences seen in bronchial biopsy specimens, and there was no evidence for up-regulation of ICAM-1 or HLA-DR expression after rIFN-gamma. We conclude that, in normal persons, rIFN-gamma can be effectively delivered by inhalation. Future trials using inhaled rIFN-gamma appear to be warranted for certain pulmonary diseases.

Administration, Inhalation↗
PubMed1993

Platypnea in the intensive care unit. A newly described cause.

Platypnea in a patient with COPD developed during the subacute onset of an ileus. Arterial blood gas studies failed to document orthodeoxia. Routine treatment for COPD failed to resolve the patient's positional dyspnea, but the dyspnea rapidly resolved following resolution of the ileus. The authors postulate that impaired abdominal muscle contraction in the upright position secondary to the ileus was responsible for the development of platypnea.

Abdominal Muscles↗
PubMed1993

Early ABRs in infants undergoing assisted ventilation.

ABR was performed on 42 preterm infants undergoing assisted ventilation with conventional or high-frequency oscillatory ventilation (HFOV). ABRs from these very young neonates were evaluated to further detail the emerging response and to determine if type of ventilation or other perinatal factors had effects on the ABR. While responses were present down to 26 weeks gestational age, the only factors which appeared related to absent ABRs were birthweight and gestational age.

Auditory Cortex↗
PubMed1992

Detection of alveolar macrophage-derived IL-1 beta in asthma. Inhibition with corticosteroids.

This study investigated alveolar macrophage function in asthma as assessed by the presence and source of the cytokine IL-1 beta. Bronchoalveolar lavage (BAL) fluid and cell pellets were obtained at 4 a.m. from a cohort of asthmatic subjects. Normal subjects were used as controls. Asthmatic BAL fluid contained 57.0 +/- 5.9 pg/ml of IL-1 beta as determined by ELISA. No IL-1 beta could be identified in the BAL fluid of the control group. This IL-1 represented synthesis by cells of the airway as assessed by the presence of IL-1 beta-specific mRNA transcripts in the BAL cell pellets. Inasmuch as IL-1 beta transcripts are known to be present for only a short time period after activation (approximately 0.5 to 16 h), the presence of transcripts represents recent cellular activation. Using the technique of in situ hybridization, IL-1 beta transcripts were found to be located exclusively within alveolar macrophages, and a mean of 40 +/- 14% of alveolar macrophage were activated at the time of the lavage. Corticosteroids are known to be efficacious in the treatment of asthma. Administration of a single 50-mg dose of prednisone at 3 p.m. resulted in diminished IL-1 beta protein concentration in the BAL fluid (28.3 +/- 5.7 pg/ml; p < 0.01 compared to baseline) and completely abrogated IL-1 beta mRNA expression. In summary, these studies demonstrate that IL-1 beta is synthesized within the airways by alveolar macrophage and suggest that IL-1 beta may be a mediator of asthma. Inhibition of IL-1 beta may be an additional mechanism for the efficacy of corticosteroids in the treatment of asthma.

Asthma↗
PubMed1992

Distribution of a fluorescent ivermectin probe, bodipy ivermectin, in tissues of the nematode parasite Ascaris suum.

A fluorescent derivative of the anthelmintic ivermectin (4''-5,7-dimethyl bodipy proprionylivermectin, referred to hereafter as bodipy ivermectin) was synthesized for an investigation of the distribution of avermectins. Injected into adult Ascaris suum at doses greater than 0.1 micron per worm, it produced a dose-dependent immobilization. Fluorescent microscopy of frozen sections revealed the distribution of the probe in the whole nematode. Staining of collagenase-isolated muscle cells was studied using bath application of bodipy ivermectin. The trypan-blue quenching technique showed that the ivermectin probe was located in the outer monolayer of the muscle membrane. The cytoplasm was not stained. The interpretation of these observations is discussed in view of the known lipophilic nature of avermectins. Staining of the muscle membrane and nerve cord is consistent with the view that avermectins act at these sites. The significance of the hypodermal and lateral line staining is also discussed.

Animals↗
PubMed1992

Effect of starvation or restriction on self-selection of macronutrients in rats.

Two models of food deprivation were used to study feeding behavior: starvation and dietary restriction. Rats starved for 3 days had decreased protein intake during the first 2 days of refeeding followed by increased carbohydrate consumption compared to controls. During refeeding, total intake was initially low compared to controls. In a second starvation study of similar design, brain tissues [raphe, ventromedial hypothalamus (VMH)] and sera were collected for analysis before refeeding and on day 2 of refeeding. Starved and starved-refed rats had increased serum beta-hydroxybutyrate versus controls. In rats restricted for 5 days (5 g/day), total food intake was increased immediately and was characterized primarily by carbohydrate intake. Serotonin levels in the raphe were decreased in restricted rats and 5-hydroxyindole acetic acid (5-HIAA) increased in restricted-refed rats. Restriction caused an increase in blood levels of beta-hydroxybutyrate and a decrease in insulin and glucose compared to controls. Fat selection remained low throughout all studies. The data suggest that starvation and food restriction elicit different patterns of macronutrient selection upon refeeding.

3-Hydroxybutyric Acid↗
PubMed1992

An anorectic agent from adipose tissue of overfed rats: effects on feeding behavior.

Parabiosis and blood-transfer studies with rodents suggest the existence of humoral factors capable of affecting energy balance. The nature and origin of these factors is undetermined. Aqueous extracts of adipose tissue from overfed rats significantly reduce food intake when administered intraperitoneally (IP) or intracerebroventricularly (ICV). We term the agent(s) responsible for this effect adipose satiety factor (ASF). A single IP dose of ASF, equivalent to 44 mg crude protein, suppresses cumulative food intake for over 12 h. ASF, prepared using a combination of adipose tissue from obese Zucker rats and overfed rats, is more potent per unit of protein than ASF prepared exclusively using adipose tissue from overfed rats. A single ICV dose of this hybrid preparation, equivalent to 14.6 micrograms of crude protein, suppresses cumulative food intake by 40% for up to 48 h. By ultrafiltration, the molecular weight associated with maximal ASF activity is between 30 and 100 kilodaltons (kDa). The behavioral specificity of ASF-induced anorexia is demonstrated using meal pattern, taste aversion, and differential starvation paradigms.

Adipose Tissue↗
PubMed1992

Novel approach to diet design for determining macronutrient preference.

Previous studies indicate that rats fed a saturated vs. unsaturated fat consume more of a high-protein/low-carbohydrate and less of a low-protein/high-carbohydrate diet. Present studies were conducted to determine whether saturated-fat-fed rats are preferring protein or avoiding carbohydrate. Three combinations of diets were prepared in which one macronutrient was held constant and two covaried: 1) high protein/low carbohydrate and low protein/high carbohydrate, 2) high fat/low carbohydrate and low fat/high carbohydrate, and 3) high fat/low protein and low fat/high protein. Male Sprague-Dawley rats (75-99 g) were fed either 34% tallow (n = 30) or corn oil (n = 30) diets for 4 days. These diets were removed and one third of each group was given one of the diet combinations. Rats previously fed tallow consumed more high-protein/low-carbohydrate and low-carbohydrate/high-fat diets and less high-carbohydrate/low-fat diet than controls previously fed corn oil. These data suggest that tallow-fed animals are avoiding carbohydrate rather than preferring protein.

Animals↗
PubMed1992

Stability of the circadian alteration in lung function in asthma.

Although studies on pharmacologic interventions for nocturnal asthma are increasing, information about the long-term stability of circadian spirometric changes or bronchial responsiveness is not known. This study was undertaken to evaluate these variables in 10 patients with asthma measured quarterly during a 1-year period. We have found that the overnight decrease in peak expiratory flow rate measurements is stable (mean range, 13.8% to 16.4%) during the year, as are the quarterly 4 PM (1600-hour) and 4 AM (0400-hour) FEV1 values. The 4 PM provocative concentration of methacholine that produced a 20% fall in FEV1 (PC20) (range of geometric mean, 0.213 to 0.359 mg/ml) and the 4 AM PC20 (range, 0.057 to 0.152 mg/ml) for the group were also relatively stable. Individual variation was higher for the PC20 values than for the FEV1. We concluded that during a 1-year period, without acute respiratory events, (1) the overnight decrement in peak expiratory flow rate and the 4 AM and 4 PM FEV1 values were constant and (2) bronchial responsiveness demonstrated some individual variability, but for the group, it remained stable.

Adult↗
PubMed1992

Somatostatin and growth hormone-releasing factor release from Zucker rat hypothalamic tissue.

Plasma somatotropin (ST) levels are depressed in the genetically obese Zucker rat compared to those of their littermates. It is believed that this defect is associated with one or both of the hypothalamic neuropeptides that control ST release: growth hormone releasing factor (GRF) and somatostatin (SS). The mechanism by which SS and GRF neuropeptides are regulated remains uncertain. The objective of this study was to examine the effect of 2 deoxy-glucose (2DG), isoproterenol (ISO), tryptophan (TRP), and 5HT on SS and GRF release in hypothalamic tissue from lean and obese Zucker rats. An in vitro perifusion system was established to examine the release of SS and GRF from perifused hypothalami taken from 8- and 12-week-old Zucker rats under basal conditions and in response to 2DG, ISO, TRP, 5HT, and KCl administration. Hypothalami were perifused with Dulbecco's modified eagle's medium continuously at 37 degrees C for 5 h at a flow rate of 100 ml/min. ISO and 2DG significantly (p < 0.05) increased SS levels from the obese rat, but no effect was observed from the lean littermate. GRF was not affected by 2DG or ISO in either genotypes. TRP and 5HT failed to affect SS or GRF release in lean or obese Zucker rats. It is proposed that the obese Zucker rat is more sensitive to glucose deprivation and to beta-adrenergic stimulation of SS release than the lean littermate.

Aging↗
PubMed1992

On the distribution of a fluorescent ivermectin probe (4" 5,7 dimethyl-bodipy proprionylivermectin) in Ascaris membranes.

The distribution of the fluorescent ivermectin derivative (4" 5,7 dimethyl bodipy proprionylivermectin, referred to here as bodipy ivermectin) was studied in muscle vesicle membranes from the parasite Ascaris suum. Incubation in bodipy ivermectin, at concentrations greater than 1 ng/ml, produced a dose-dependent fluorescence in the vesicles. The level of fluorescence was not depressed (but increased) by prior incubation with 1 microM unlabelled ivermectin. This observation suggested that most of the bodipy ivermectin was free in the lipid phase of the membrane and not associated with a receptor. The trypan blue quenching technique showed that the bodipy ivermectin did not cross the membrane bilayer but remained in the outer monolayer. Lateral mobility of the probe in the membrane was studied using the fluorescence recovery after photobleaching (FRAP) technique. The lateral diffusion coefficient (DL) was 14.0 x 10(-10) cm2/s which was nearly three times faster than the lipid probe octadecanoyl-aminofluorescein in membranes from the same preparations; only 46% of the probe was mobile, showing that within a 1.2 microns radius the distribution of the bodipy ivermectin in the membrane was not homogeneous. These observations are used to suggest that: the site of action of ivermectin is located in the outer monolayer of the membrane (possibly on the Cl- channel); and that the speed of onset of action in isolated membrane preparations may be limited by diffusion in the membrane.

Animals↗
PubMed1992

Disturbances of person identification in Alzheimer's disease. A retrospective study.

Person identification disturbances in Alzheimer's disease (AD) add to the suffering of both patients and caregivers. We assessed the prevalence of person identification disturbances in the records of 217 outpatients with AD. These disturbances occurred in 25.4% (N = 55) and included transient misidentifications of familiar persons (N = 34), the Capgras syndrome (N = 11), misidentification of themselves in mirrors (N = 5), prosopagnosia (N = 3), misidentification of unfamiliar persons as familiar (N = 1), and misidentification of another person as oneself (N = 1). Transient misidentifications were easily corrected misperceptions, and the Capgras syndrome and mirror difficulties were associated with suspiciousness/paranoia and delusions. In AD, these findings suggest that misidentifications of familiar persons result from misinterpretations due to cognitive impairments, and the Capgras syndrome and mirror difficulties ensue when these misinterpretations are elaborated by paranoid delusions.

Aged↗
PubMed1992

The effect of dietary fat on diet selection may involve central serotonin.

Rats consuming a diet of 34% tallow select more protein and less carbohydrate than rats fed either 5% corn oil or tallow or 34% corn oil (25). To examine potential mechanism(s) of this phenomenon, we fed rats diets containing either tallow or corn oil at levels of 5 or 34% for 2 days. Sera were analyzed, and rats fed 34% tallow had higher serum insulin compared with those fed 34% corn oil. In a second experiment, rats were fed either 34% corn oil or tallow for 2 days. Brain tissues were analyzed, and rats fed 34% tallow had elevated serotonin in the raphe area compared with those fed 34% corn oil. In a third experiment, rats were fed either 34% corn oil or tallow for 2 days and then given dl-fenfluramine before diet selection. Fenfluramine depressed food intake to a greater degree in rats fed 34% tallow compared with those fed corn oil. These findings suggest that the diet selection behavior observed in tallow-fed rats may be mediated by a central serotonin system.

Animals↗