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Biomedical subjects

R J Martin

Publications and source records attributed to R J Martin.

At least 325 records · Page 18Linked to original sources
PubMed1989

In vitro evidence for an inhibitor of lipogenesis in serum from overfed obese rats.

Involvement of a humoral agent in regulation of energy balance has been demonstrated by parabiosis experiments. Overfed obese rats produce a blood-borne factor that inhibits adipose fatty acid synthesis in their partners, resulting in loss of body fat without significant inhibition of food intake. An in vitro bioassay was developed to test small serum samples for antilipogenic activity. Epididymal adipocytes from ad libitum-fed rats were preincubated for 12 h with 2% serum. Basal adipocyte fatty acid synthesis, measured in a subsequent serum-free incubation, was inhibited by obese serum. Insulin response was not changed. Characterization studies indicated that the factor was probably a protein, larger than 30 kDa, but not a protease or a low-density lipoprotein and was not associated with serum albumin. Physiological experiments demonstrated that the agent was produced when body weight was raised substantially above "set-point." Inhibitory activity was neither species specific nor pituitary dependent. Structure, origin, and physiological significance of the factor are unknown, but it may be involved in the control of body fat content.

Adipose Tissue↗
PubMed1989

Level of satiety: in vitro energy metabolism in brain during hypophagic and hyperphagic body weight recovery.

Rates of in vitro glucose and fatty acid oxidation were examined in four brain sites during hypophagic and hyperphagic recovery of normal body weight. Rats were fed 40, 100, or 160% of normal intake, via gastric intubation, for 3 wk. Another group of rats was starved until body weight loss was equivalent to weight loss in 40%-fed rats. Groups of rats were killed at the conclusion of tube feeding or fasting and at specific periods during recovery of body weight. Brain sites examined were the ventrolateral hypothalamus (VLH), ventromedial hypothalamus (VMH), a caudal brain stem site encompassing the area postrema-nucleus of the solitary tract (AP-NTS), and cortex. During recovery, rats previously fed 160% of normal intake (anorectic) maintained low rates of VLH fatty acid oxidation and were hypophagic until most excess fat was depleted. Conversely, rats previously fed 40% of normal intake (hungry) maintained high rates of VLH fatty acid oxidation and were hyperphagic until most deficient fat was repleted. Rats previously starved maintained high rates of VLH fatty acid oxidation during hyperphagic recovery, although levels of VLH fatty acid oxidation and food intake were initially low on refeeding. Rates of glucose oxidation in the brain sites examined did not relate well to energy balance status and the needed adjustments in food intake. The results indicated that the level of glucose oxidation in the VLH and AP-NTS responded to the level of energy immediately coming into the system (food intake).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effects of unilateral nasal occlusion on ventilation and pulmonary resistance in infants.

Because neonates are vulnerable to spontaneous nasal obstruction, this study was designed to evaluate the ventilatory consequences of obstructing a single nasal passage in preterm infants. We employed a nasal pneumotachograph that separately quantified airflow between the two nasal passages and permitted unilateral nasal mask occlusions. Changes in minute ventilation (VI) and total (RT) and inspiratory pulmonary resistance (RI) were measured in response to 30-s unilateral occlusions during quiet and active sleep in 11 subjects. Unilateral nasal obstruction caused VI to fall significantly in both sleep states, because of a fall in both tidal volume and respiratory rate, without alteration in transcutaneous blood gases. RT and RI increased by 27 and 24 cmH2O.1-1.s, respectively, during unilateral nasal occlusion; this increase was greater than would be expected solely from elimination of one nasal passage. In 7 of the 11 infants a single dominant side could be identified as contributing 56-67% to tidal volume. The effect of occlusion on VI, RT, or RI did not differ whether the dominant or nondominant side was occluded. We conclude that unilateral nasal mask occlusion increases RT and RI and decreases VI in preterm infants. The larger than expected increase in resistance suggests that unilateral nasal loading predisposes to narrowing of the extrathoracic airway, and this may explain the comparable ventilatory responses to occluding the dominant and nondominant nasal passage.

Airway Obstruction↗
PubMed1989

Effect of sleep on nocturnal bronchoconstriction and ventilatory patterns in asthmatics.

To assess the effect of sleep on airflow resistance and patterns of ventilation in asthmatic patients with nocturnal worsening, 10 adult subjects (6 asthmatic patients with nocturnal worsening, 4 normal controls) were monitored overnight in the sleep laboratory on two separate occasions. During 1 night, subjects were allowed to sleep normally, whereas during the other night all sleep was prevented. The six asthmatic patients demonstrated progressive increases in lower airway resistance (Rla) on both nights, but the rate of increase was twofold greater (P less than 0.0001) during the sleep night compared with the sleep prevention night. However, overnight decrements in forced expired volume in 1 s (FEV1) were similar over the 2 nights. The asthmatic patients maintained their minute ventilation as Rla increased during sleep, demonstrating a stable tidal volume with a mild increase in respiratory frequency. We conclude that in asthmatic patients with nocturnal worsening 1) Rla increases and FEV1 falls overnight regardless of sleep state, 2) sleep enhances the observed overnight increases in Rla, and 3) sleep does not abolish compensatory ventilatory responses to spontaneously occurring bronchoconstriction.

Adult↗
PubMed1989

Diaphragm, genioglossus, and triangularis sterni responses to poikilocapnic hypoxia.

Both isocapnic and poikilocapnic hypoxia may elicit a biphasic respiratory response, during which an initial ventilatory stimulation is followed by a reduction in breathing and diaphragm (DIA) electrical activity. To ascertain whether during adulthood other respiratory muscles have biphasic hypoxic responses similar to the DIA, in nine anesthetized cats electromyograms (EMG) were recorded from the DIA, genioglossus (GG), and triangularis sterni (TS) (n = 7) muscles during poikilocapnic hypoxia. DIA and GG EMG started at 60 +/- 4 and 9 +/- 3 units, respectively, during O2 breathing, increased to a maximum of 100 units during the 10-min hypoxic stimulus, and subsequently declined to 81 +/- 6 and 58 +/- 12 units, respectively, by the end of 10 min of hypoxia. The time course of the increase and subsequent decline was similar for the DIA and GG and for GG activity during both inspiration and expiration. Furthermore the degree to which GG EMG declined after reaching its peak activity level correlated with the magnitude of the respective decline in DIA EMG (r = 0.79, P less than 0.02). The TS, in contrast, was maximally active either during O2 breathing or very early during hypoxia, and its activity declined progressively thereafter (to 13 +/- 6% of its peak value at the end of 10 min of hypoxia). The degree to which TS EMG declined did not correlate with the degree to which DIA or GG EMG declined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Nocturnal asthma therapy. Inhaled bitolterol versus sustained-release theophylline.

Many asthmatics complain of increased symptoms, awakenings, and need for additional medications during the sleeping hours. Sustained-release theophylline (THEO) may be superior to conventional inhaled bronchodilators in preventing nocturnal asthma symptoms and the early morning decrement in lung function common to this population. However, recent studies have demonstrated that THEO may delay sleep onset and perturb sleep stage distribution. No previous study has evaluated electroencephalographic, cardiac, and gas exchange indices during sleep in asthmatics treated with THEO compared with a long-acting inhaled beta 2-agonist. The study goals were to determine if theophylline perturbed sleep when compared with beta 2-agonists and to determine which agent achieved best control of daytime and nocturnal pulmonary symptoms and lung dysfunction. We evaluated 26 subjects with mild to moderate asthma and a history of frequent nocturnal symptoms who previously demonstrated decrements in AM lung function. THEO was compared with 3 puffs every 8 h (6 A.M., 2 P.M., and 10 P.M.) of bitolterol (BITOL), a long-acting beta 2-agonist, in a randomized, double-blind, placebo-controlled cross-over study. Each drug was administered for a 2-wk period ending with two consecutive nights of sleep evaluation followed by cross-over to the alternate drug regimen. During THEO administration, plasma concentrations on awakening were 11.4 +/- 0.69 micrograms/ml as compared with 0.00 micrograms/ml during BITOL. THEO was not found to disrupt sleep as sleep latency, total sleep time, percentage of total sleep time spent in Stages 1, 2, and 3/4 and in REM sleep were similar during each regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1989

Circadian variations in theophylline concentrations and the treatment of nocturnal asthma.

The nocturnal worsening of asthma is a common problem that can be difficult to treat. Two different sustained-release theophylline preparations were used to determine (1) if the serum theophylline concentrations (STC) depend on the type and dosing schedule of the preparation, (2) the relationship between STC and the circadian variations in asthma, and (3) the effect of STC on sleep quality and respiratory patterns during the night. In 16 subjects with nocturnal asthma, the STC were significantly higher during the daytime on twice-daily versus once-daily theophylline preparations given at 7 P.M., but the FEV1 values were similar. During the night, the STC were significantly higher with the once-daily regimen, and the awakening FEV1 value was also improved (p less than 0.05). All polysomnographic variables were similar between the two preparations, except that with the once-daily preparation there was a decreased number of hypopneas (p less than 0.05) and fewer minutes below an oxygen saturation of 90% (p less than 0.05). We conclude that patients with nocturnal asthma need their treatment focused on the nocturnal portion of the circadian cycle and that higher STC during this critical time period are beneficial without interfering with sleep quality.

Adult↗
PubMed1989

Genioglossus and diaphragm activity during obstructive apnea and airway occlusion in infants.

To document mechanisms contributing to upper airway collapse, we compared the electromyographic activity of the genioglossus (GG) and diaphragm (DIA) during spontaneous mixed and obstructive apnea and during induced end-expiratory airway occlusion in 11 premature infants. In addition to ventilation and esophageal pressure measurements, we obtained DIA and GG electromyograms (EMG) from subcostal and sublingual surface electrodes, respectively. Amplitude of the DIA EMG and the frequency of occurrence of the GG EMG were determined for: 1) the breath preceding apnea or occlusion, 2) the initial and last obstructed inspiratory efforts, and 3) the first breath at resolution of both apnea and occlusion. During spontaneous apnea with airway obstruction amplitude of the DIA, EMG decreased on the initial obstructed inspiratory effort and did not exceed that of the breath preceding apnea until reestablishment of flow. In contrast, during end-expiratory airway occlusion, the amplitude of the DIA EMG increased both during and at release of occlusion. In 18 +/- 6% of the spontaneous apneic episodes, GG EMG was present with the breath preceding apnea and this frequency did not increase significantly until resolution of the apnea. During induced airway occlusion, GG EMG was not present with the breath preceding occlusion but its frequency did increase to 58 +/- 8 and 42 +/- 8% with the last occluded inspiratory effort and the first breath after release of occlusion, respectively. The decreased presence of the GG EMG from the last occluded effort to the breath at release of occlusion (58 +/- 8 versus 42 +/- 8%, p less than 0.05) was probably due to the greater mechanoreceptor-mediated inhibition associated with reestablishment of flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Obstruction↗
PubMed1989

Alterations in adipogenic and mitogenic activity of porcine serum in response to hypophysectomy.

The importance of the pituitary in postnatal regulation of peripheral preadipocyte proliferation and differentiation was examined by hormone supplementation of hypophysectomized pig serum in primary cultures of preadipocyte and stromal-vascular cells derived from rat inguinal adipose tissue. Hypophysectomized pig serum promoted at least 25% less preadipocyte proliferation, less differentiation of sn-glycerol-3-phosphate dehydrogenase activity, and less histochemical differentiation than serum from intact pigs. Porcine GH supplementation of hypophysectomized serum-stimulated [3H]thymidine incorporation by preadipocytes and stromal cells and also histochemical differentiation of preadipocytes, but not enzymatic differentiation. Insulin-like growth factor I (IGF-I) stimulated [3H]thymidine incorporation by preadipocytes and stromal cells. Enzyme differentiation by developing cells was stimulated by IGF-I. Hydrocortisone supplementation of hypophysectomized serum inhibited [3H]thymidine incorporation and stimulated enzymatic differentiation. Thyroid hormones (T3 and T4) stimulated [3H]thymidine incorporation by preadipocytes in a dose-responsive manner when supplemented to hypophysectomized serum. Thyroid hormones stimulated differentiation of enzyme activity at the lowest concentrations examined. The mitogenic effects of GH, IGF-I, and T4 were not specific to the preadipocyte population, since the stromal-vascular cells responded in a similar manner. However, hypophysectomy resulted in a specific reduction in preadipocyte proliferation while stimulating multiplication of stromal-vascular cells. These results suggest that these hormones are nonspecific mitogens in adipose tissue, while unidentified factors of pituitary origin may be important for the specific regulation of proliferation of preadipocytes. Additionally, hypophysectomy appears to remove mitogenic inhibitors that are specific for the stromal-vascular cells.

Adipose Tissue↗
PubMed1989

Effect of ractopamine on insulin sensitivity and response of isolated rat adipocytes.

In vitro effects of the phenethanolamine ractopamine on basal and insulin-stimulated lipid metabolism were determined in adipocytes isolated from epididymal fat pads of Sprague-Dawley rats. Ractopamine appeared to be equipotent to the catecholamine isoproterenol in stimulating basal lipolysis and inhibiting basal lipogenesis, producing maximum effects at 10(-6) M. Addition of a half-maximally stimulating dose of ractopamine (5 x 10(-8) M) to the incubation media decreased insulin sensitivity but not insulin responsiveness of the cells, stimulating lipolysis and inhibiting lipogenesis only in the presence of low media insulin concentrations. This effect was totally reversed by 10 microM/propranolol. Maximally effective concentrations of ractopamine (10(-6) M) significantly decreased both the sensitivity and responsiveness of the isolated adipocytes to insulin. Addition of 10 microM propranolol to the incubation media effectively reversed the lipolytic and anti-lipogenic effects of 10(-6) M ractopamine observed at media insulin concentrations greater than 25 microU/ml, whereas it only partially reduced the ractopamine-induced effects observed at lower insulin concentrations. The results demonstrate 1) that ractopamine has concentration-dependent effects on adipose tissue insulin sensitivity and responsiveness and 2) that these effects may be mediated, in part, through beta-adrenergic receptors.

Adipose Tissue↗
PubMed1989

Regulation of gene expression during adipocyte differentiation: a review.

The differentiation of adipose precursor cells is accompanied by the acquisition of adipocyte-specific messenger (m) RNAs allowing characteristic changes in protein composition. The development of methods for cloning and characterizing individual genes has provided the opportunity to study selective gene expression by adipocytes at the molecular level. In this review, the information obtained to date regarding transcriptional and post-transcriptional regulatory mechanisms utilized by adipocytes is summarized. Included are descriptions of conserved DNA sequences found in noncoding regions of adipose genes and of how protein-DNA interactions at these regions are thought to regulate the initiation of transcription. Among the transcription factors implemented in regulation of adipocyte-specific gene expression are the protein product of the proto-oncogene c-fos, the triiodothyronine receptor and steroid hormone receptors. Data also are discussed that indicate that RNA editing and determinants of mRNA stability contribute to the adipocyte phenotype. It is hoped that a review of the regulatory aspects of gene expression during adipocyte differentiation will identify areas deserving further study by researchers interested in understanding adipose development.

Adipose Tissue↗
PubMed1989

Changes in lipogenesis and lipolysis associated with recovery from reversible obesity in mature female rats.

Reversible obesity provides a model for demonstration of weight regulation in mature animals. Changes in body composition and in vitro adipose and hepatic lipid synthesis and adipose lipolysis of rats recovering from enforced weight gain were examined to determine whether correction of weight was facilitated by metabolic changes independent of those resulting from hypophagia and negative energy balance. Female Sprague-Dawley rats (200 g) were divided into three groups. Controls ate ad libitum, tube-fed control rats were weight matched to controls. Two-hundred percent-fed rats were tube-fed twice control intake. After 26 days tube feeding stopped and a subgroup from each treatment was killed for determination of body composition and in vitro tissue metabolism. Further subgroups were examined 5, 10, 15, and 36 days later. At the end of overfeeding 200%-fed rats were hypophagic and had high rates of adipose and hepatic lipid synthesis, which soon returned to normal. Gross changes in body fat mass were corrected by hypophagia and increased adipose lipolysis. The remaining small excess in body fat appeared to be corrected by decreased basal and insulin-stimulated adipose fatty acid synthesis when food intake had returned to normal.

Adipose Tissue↗
PubMed1989

Growth hormone treatment reduces total body fat accumulation in Zucker obese rats.

Lean and obese Zucker rats were injected daily intraperitoneally with high doses (5-10 mg/kg) of human growth hormone (GH) for 3 weeks. In the obese rats after GH treatment, carcass lipid was decreased by 50 percent, and bone weight increased to levels of lean controls. During the last two weeks of GH treatment, food intake was increased in lean rats and not significantly affected in obese rats. Loss of body weight in obese animals was masked by water retention. Serum insulin concentrations were doubled in obese animals but unchanged in lean phenotypes after GH treatment. Hepatic fatty acid oxidation in obese animals was stimulated 5-fold by treatment, while hepatic lipid synthesis was stimulated 2-fold and adipose lipid synthesis was reduced 3-fold. These results suggest that growth hormone induces a partitioning of nutrients in obese rats which results in less lipid accumulation.

Adipose Tissue↗
PubMed1989

Neck and body position effects on pulmonary mechanics in infants.

Pulmonary mechanics and ventilatory parameters were measured in 30 former preterm infants at a postterm age of 8 to 10 months. All subjects had required assisted ventilation in the neonatal period and 16 had a history of bronchopulmonary dysplasia. Each infant was studied in both supine and semisitting positions, and in each body position the infants were studied with neutral, flexed, and extended neck positions. Baseline measurements (body supine, neck neutral) and the response to postural changes did not differ between infants who had had bronchopulmonary dysplasia and those who had not. Change in body position from supine to semisitting decreased total pulmonary resistance (P less than .05) and increased specific lung compliance (P less than .01). Neck flexion increased resistance (P less than .001) in both body positions but did not influence compliance. These postural effects are consistent with an increase in functional residual capacity in the semisitting position and a decrease in pharyngeal area during neck flexion. Thus, posture needs to be precisely controlled during pulmonary function testing in infants. Furthermore, optimal neck and body position may improve their clinical status.

Airway Resistance↗
PubMed1988

Evidence for neuroendocrine regulation of preadipocyte proliferation and differentiation.

Cells in fetal adipose tissue and cells in vitro are characterized by rapid proliferation. Serum factors have been shown to be important for the rapid proliferation of cells in vitro. The present experiment was performed to determine if neuroendocrine regulatory mechanisms of the fetus can influence the actions of serum factors on preadipocyte proliferation and differentiation in vitro. Sera were obtained from decapitated fetal pigs and intact littermates during gestation. Sera were tested for their effects on primary cultures of preadipocytes and stromal-vascular cells derived from inguinal adipose tissue of young Sprague-Dawley rats. Coverslip cultures were used for histochemical analysis of enzymes after 12 days of incubation with test media. Analysis of growth curves produced from sequential [3H]-thymidine labeling indicated that fetal age influences rates of proliferation. Sera from decapitated fetal pigs specifically reduced the number of proliferating preadipocytes in culture. Sera from decapitated fetal pigs induced a minimum of 50% less differentiation of sn-glycerol-3-phosphate dehydrogenase activity than sera from intact pigs at all fetal ages. Histochemical staining for enzymes of differentiating preadipocytes was also reduced in cultures incubated with sera from decapitated fetal pigs in comparison to sera from intact pigs. The present study has demonstrated that the in vivo effect of decapitation on fetal adipose tissue development is a consequence of alterations in systemic factors present in serum in response to removal of central regulation by the hypothalamic-pituitary axis.

Adipose Tissue↗