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Biomedical subjects

J R Catterall

Publications and source records attributed to J R Catterall.

At least 37 records · Page 2Linked to original sources
PubMed1987

In vivo and in vitro activation of alveolar macrophages by recombinant interferon-gamma.

In vivo administration of recombinant interferon-gamma (rIFN-gamma) was previously shown to result in activation of the microbicidal activities of peritoneal macrophages (PM phi). Because macrophages at different anatomical sites vary in their functional capacities, we considered it of interest to determine whether administration of murine rIFN-gamma, either in vitro or in vivo, can enhance the microbicidal activity of resident alveolar macrophages (AM phi) and to compare the effects of rIFN-gamma on AM phi and PM phi. After incubation in vitro with rIFN-gamma, the antimicrobial activities of both murine AM phi and PM phi were enhanced, as assessed by their ability to inhibit replication of the intracellular parasite, Toxoplasma gondii. This effect was dose dependent for AM phi over a range of 0.1 to 1 U/ml and for PM phi over a range of 0.5 to 1000 U/ml. In this assay, the minimum dosage required for in vitro activation of AM phi was one-half that required for activation of PM phi, suggesting a greater sensitivity of AM phi to the in vitro activity of rIFN-gamma. Macrophages from both anatomical sites were also activated when rIFN-gamma was administered in vivo. This effect was dose dependent over a range of 10(3) to 10(5) U/mouse. Freshly harvested AM phi and PM phi from mice injected 24 hr earlier with 10(4) U rIFN-gamma by either the i.v. or i.p. routes markedly inhibited intracellular multiplication of Toxoplasma. In contrast, AM phi and PM phi from control mice permitted fourfold to ninefold increases in numbers of intracellular Toxoplasma. The anti-toxoplasma activity of AM phi and PM phi gradually diminished over a period of 3 days when assayed at successive 24 hr periods after a single i.v. injection of rIFN-gamma. At 3 days after injection, a substantial loss of anti-toxoplasma activity was observed with PM phi as compared with controls; residual anti-toxoplasma activity was still demonstrable in AM phi at 3 days. These results demonstrate that in vitro as well as in vivo treatment with rIFN-gamma confers on AM phi an enhanced antimicrobial activity. These findings provide a rationale for evaluating rIFN-gamma in the treatment of pulmonary infections, especially those due to opportunistic pathogens against which AM phi play a major role in host defense.

Cytotoxicity, Immunologic↗
PubMed1987

Nonoxidative microbicidal activity in normal human alveolar and peritoneal macrophages.

Although Toxoplasma gondii multiplies within normal murine alveolar and peritoneal macrophages, it is killed by normal rat alveolar and peritoneal macrophages. The killing by rat macrophages is by a nonoxidative mechanism. Studies on normal human alveolar macrophages have reported disparate results in regard to their ability to inhibit or kill T. gondii. We considered it of interest to explore further the effect of normal human alveolar and peritoneal macrophages on T. gondii. Unstimulated alveolar macrophages from each of seven individuals demonstrated a marked ability to kill or inhibit multiplication of T. gondii in vitro (e.g., the number of parasites per 100 alveolar macrophages was 31 at time zero and 2 at 18 h, whereas this value increased from 37 at time zero to 183 at 18 h in murine macrophages assayed in parallel). In quantitative assays of superoxide, alveolar macrophages released a substantial amount of superoxide when exposed to phorbol myristate acetate or to candidae. In contrast, alveolar macrophages incubated with T. gondii released no more superoxide than when in medium alone. Scavengers of superoxide anions, hydrogen peroxide, singlet oxygen, and hydroxyl radicals failed to inhibit killing of T. gondii by alveolar macrophages. Peritoneal macrophages from each of six normal women undergoing laparoscopy killed T. gondii in vitro; results of quantitative superoxide assays and scavenger experiments demonstrated that no oxidative burst was triggered in these macrophages by exposure to T. gondii. These data indicate that normal human alveolar and peritoneal macrophages can kill an intracellular parasite by nonoxidative mechanisms and suggest that these mechanisms are important in inhibition or killing of other opportunistic intracellular pathogens.

Adult↗
PubMed1987

Breathing patterns during sleep in patients with nocturnal asthma.

Breathing patterns early and late in the night, at the same sleep stage, were compared in six healthy subjects and 15 adults with nocturnal asthma, to try to identify changes of overnight bronchoconstriction, and breathing patterns at different sleep stages, to see whether there were changes related to sleep stages that were indicative of bronchoconstriction. Despite an average 31% fall in FEV1 overnight in the patients with asthma, neither breathing frequency nor expiratory time, which might be expected to change during bronchoconstriction, was different early in the night from late in the night, nor did they differ between sleep stages. There was no evidence of asynchronous movement of the chest and abdomen in any patient. This study did not identify any abnormality of breathing pattern that would indicate the development of nocturnal asthma without the need to awaken the patient.

Adolescent↗
PubMed1987

Unique differences in infectivity and seroreactivity of Toxoplasma harvested from mice infected for different lengths of time.

For use in experiments, Toxoplasma of the RH strain are usually harvested from mouse peritoneal cavities 48 hr (2-day Toxoplasma) or more after intraperitoneal inoculation. In this report we show that Toxoplasma harvested at 24 hr (1-day Toxoplasma) after inoculation are much more infective for and replicate to a greater degree within mouse resident peritoneal macrophages in vitro and are much more resistant to the cidal activity of activated mouse peritoneal macrophages and resident rat peritoneal macrophages than are 2-day Toxoplasma. Ingestion of 1-day Toxoplasma by macrophages did not trigger the respiratory burst as measured by reduction of nitroblue tetrazolium (NBT), but coating 1-day Toxoplasma with specific antibody did result in reduced NBT. However, coating 1-day Toxoplasma with specific antibody did not markedly decrease infectivity for macrophages in vitro, unlike decreased infectivity observed when 2-day Toxoplasma are coated with specific antibody. Use of 1-day Toxoplasma in the dye test resulted in a 5-fold decrease in titer of specific antibody in human sera. Use of Toxoplasma harvested 24 hr after infection may serve as a new tool to probe virulence factors of Toxoplasma and of host cells' antimicrobial mechanisms.

Animals↗
PubMed1986

Activity of recombinant tumor necrosis factor on Toxoplasma gondii and Trypanosoma cruzi.

Activated macrophages produce tumor necrosis factor (TNF), a cytokine with anti-tumor and anti-plasmodia activities. This study revealed that recombinant TNF (rTNF) inhibits intracellular multiplication of blood trypomastigotes of Trypanosoma cruzi in murine peritoneal macrophages. rTNF did not have any apparent direct effect on the survival of extracellular T. cruzi or on its ability to infect mammalian cells. The degree of inhibition of the intracellular multiplication of T. cruzi was found to be a function of the time of exposure of the infected cells to rTNF. rTNF induced a comparable effect when different strains of the parasite were used. In contrast to its activity on T. cruzi, rTNF did not affect intracellular multiplication of Toxoplasma gondii tachyzoites or bradyzoites in normal murine peritoneal macrophages or in human fibroblasts. Killing of Toxoplasma tachyzoites by activated macrophages was not enhanced by rTNF.

Animals↗
PubMed1986

Do asthmatics suffer bronchoconstriction during rapid eye movement sleep?

Many patients with asthma are troubled by nocturnal wheeze. The cause of this symptom is unknown, but sleep is an important factor. A study was carried out to determine whether nocturnal bronchoconstriction is related to any specific stage of sleep. Eight asthmatics with nocturnal wheeze and eight control subjects performed forced expiratory manoeuvres immediately after being woken from rapid eye movement (REM) or non-REM sleep, wakings being timed to differentiate temporal effects from those related to the stage of sleep. The control subjects showed no significant temporal bronchoconstriction or bronchoconstriction related to the stage of sleep. All patients showed bronchoconstriction overnight, the mean peak expiratory flow rate falling from 410 (SEM 50) 1/min before sleep to 186 (49)1/min after sleep. After the patients had been woken from REM sleep the forced expiratory volume in one second was on average 300 ml lower (p less than 0.02) and peak expiratory flow rate 45 1/min lower (p less than 0.03) than after they had been woken from non-REM sleep. As wakenings from REM sleep were 21(8) minutes later in the night than those from non-REM sleep multivariate analysis was performed to differentiate temporal effects from those related to the stage of sleep. This showed that the overnight decreases in forced expiratory volume in one second and peak expiratory flow rate were significantly related both to time and to REM sleep. This study suggests that asthmatics may suffer bronchoconstriction during REM sleep.

Adolescent↗
PubMed1986

Oxygen-independent killing by alveolar macrophages.

We have found that normal alveolar macrophages can kill an intracellular parasite by a mechanism that does not involve toxic metabolites of oxygen. We studied the interaction between Toxoplasma gondii and rat alveolar macrophages in vitro. We were interested in Toxoplasma because it causes pneumonia in immunosuppressed patients but not in healthy individuals, and we chose the rat because it resembles immunocompetent human subjects in being resistant to T. gondii. Resident rat alveolar macrophages could kill large numbers of T. gondii. This occurred without a respiratory burst as judged by intracellular reduction of nitroblue tetrazolium and quantitative release of superoxide. Furthermore, scavengers of toxic oxygen metabolites had no effect on the toxoplasmacidal activity of the alveolar macrophages, nor did prior exhaustion of their respiratory burst with PMA. Whereas acid pH (e.g., 4.5-6.0) rapidly kills extracellular T. gondii, raising of the intralysosomal acid pH of rat alveolar macrophages by incubating them with weak bases did not inhibit their ability to kill T. gondii. Killing of Toxoplasma occurred within 1 h of initial exposure to the alveolar macrophages. However, there was no evidence that killing preceded ingestion; Toxoplasma attached to the surface of the cell appeared viable, and when phagocytosis was blocked with sodium fluoride the organisms survived. These results indicate that rat alveolar macrophages possess a powerful nonoxidative microbicidal mechanism, which is distinct from acidification of the phagolysosome but which probably involves phagosome formation. This mechanism may be clinically relevant, for we have recently observed that human alveolar macrophages also kill T. gondii by an oxygen-independent process.

Ammonium Chloride↗
PubMed1986

Sodium cromoglycate in nocturnal asthma.

To investigate whether mast cell degranulation was important in producing nocturnal asthma, the effect of a single high dose of nebulised sodium cromoglycate on overnight bronchoconstriction, oxygen saturation, and breathing patterns in eight patients with nocturnal wheeze was examined. The study took the form of a double blind placebo controlled crossover comparison. Treatment with cromoglycate did not reduce the overnight fall in FEV1 or FVC, although it was associated with improved nocturnal oxygenation. This study suggests that mast cell degranulation may not be important in the pathogenesis of nocturnal asthma.

Adolescent↗
PubMed1986

Effect of sleep deprivation on overnight bronchoconstriction in nocturnal asthma.

Nocturnal cough and wheeze are common in asthma. The cause of nocturnal asthma is unknown and there is conflicting evidence on whether sleep is a factor. Twelve adult asthmatic subjects with nocturnal wheeze were studied on two occasions: on one night subjects were allowed to sleep and on the other they were kept awake all night, wakefulness being confirmed by electroencephalogram. Every patient developed bronchoconstriction overnight both on the asleep night, when peak expiratory flow (PEF) fell from a mean (SE) of 418 (40) 1 min-1 at 10 pm to 270 (46) 1 min-1 in the morning, and on the awake night (PEF 10 pm 465 (43), morning 371 (43) 1 min-1). The morning values of PEF were, however, higher (p less than 0.1) after the awake night and both the absolute and the percentage overnight falls in PEF were greater when the patients slept (asleep night 38% (6%), awake night 20% (4%); p less than 0.01). This study suggests that sleep is an important factor in determining overnight bronchoconstriction in patients with nocturnal asthma.

Adult↗
PubMed1985

Mechanism of transient nocturnal hypoxemia in hypoxic chronic bronchitis and emphysema.

In five patients with hypoxic chronic bronchitis and emphysema we measured ear O2 saturation (SaO2), chest movement, oronasal airflow, arterial and mixed venous gas tensions, and cardiac output during nine hypoxemic episodes (HE; SaO2 falls greater than 10%) in rapid-eye-movement (REM) sleep and during preceding periods of stable oxygenation in non-REM sleep. All nine HE occurred with recurrent short episodes of reduced chest movement, none with sleep apnea. The arterial PO2 (PaO2) fell by 6.0 +/- 1.9 (SD) Torr during the HE (P less than 0.01), but mean arterial PCO2 (PaCO2) rose by only 1.4 +/- 2.4 Torr (P greater than 0.4). The arteriovenous O2 content difference fell by 0.64 +/- 0.43 ml/100 ml of blood during the HE (P less than 0.05), but there was no significant change in cardiac output. Changes observed in PaO2 and PaCO2 during HE were similar to those in four normal subjects during 90 s of voluntary hypoventilation, when PaO2 fell by 12.3 +/- 5.6 Torr (P less than 0.05), but mean PaCO2 rose by only 2.8 +/- 2.1 Torr (P greater than 0.4). We suggest that the transient hypoxemia which occurs during REM sleep in patients with chronic bronchitis and emphysema could be explained by hypoventilation during REM sleep but that the importance of changes in distribution of ventilation-perfusion ratios cannot be assessed by presently available techniques.

Adult↗
PubMed1985

Breathing and oxygenation during sleep are similar in normal men and normal women.

Most patients with the sleep apnea syndrome are male, and it has been suggested that there is a fundamental sex difference in breathing during sleep. To explore this we measured overnight ear oxygen saturation (SaO2), breathing patterns, and electroencephalographic sleep stage in 21 healthy nonobese women (10 premenopausal, 11 postmenopausal) and in 19 healthy nonobese men of similar age. Sleep duration averaged 6 h 51 min (range 343 to 468 min). The 21 older (greater than 45 yr) subjects had more episodes of apnea and hypopnea (p less than 0.01) and became more hypoxemic (p less than 0.02) than did the 20 younger subjects, but there was no sex difference, either in the younger or older subjects, in irregular breathing or nocturnal hypoxemia. Seven subjects 51 to 68 yr of age (4 men and 3 women) had more than 30 episodes of apnea and/or hypopnea and/or SaO2 decreases below 90%, but the clinical importance of this finding is unclear, 6 of the 7 being alive and 5 asymptomatic at an average of 47 months (range 5 to 67) later. Thus, irregular breathing and hypoxemia during sleep are common in both sexes older than 50 yr of age. Previous reports of a sex difference are probably explained by poor matching of the men and women, particularly with regard to body weight.

Adult↗
PubMed1984

Fitness facilitates sleep.

Eight army recruits were studied at the start, middle, and end of their initial 18-week training programme. At each point the subjects were studied for four consecutive nights in the sleep laboratory. Their sleep was characterized by the means of the recordings on the last two nights. Within 2 days of the sleep recordings (but never on the same day) each subject spent 2 non-consecutive days in the exercise laboratory. On the 1st day a maximum oxygen consumption (VO2 max) measurement was performed on a treadmill and on the 2nd day a 24-min progressive exercise bicycle ergometer test was carried out with simultaneous venous sampling (for lactic acid measurements) and oxygen consumption recordings from which the lactate turn point (LTP) was calculated. LTP was used as a measure of fitness. Approximately 1 week after the above measures lean muscle mass as calculated by total body potassium estimation was obtained for each subject. Slow wave sleep (SWS) as a percentage of total sleep time increased significantly between the start and the measurements at 9 and 18 weeks, being 21.9%, 29.9%, and 28.5% respectively. Anaerobic threshold increased significantly (P less than 0.05) over the first 9 weeks and continued to increase to the end of the training period (P less than 0.001) using VO2 when lactate level was 2 mmol/l as a percentage of VO2 max. With increase in fitness, sleep onset latency and wake time during sleep decreased and sleep efficiency improved. The results suggest that as fitness increases sleep quality improves.

Adolescent↗
PubMed1984

Breathing, sleep, and diabetic autonomic neuropathy.

Sudden, unexplained deaths are relatively common in diabetic autonomic neuropathy. As disturbed autonomic function has been associated with sleep apnea, and sleep apnea with sudden death, we recorded breathing patterns, arterial oxygen saturation, and EEG during sleep in 8 male diabetic subjects with severe autonomic neuropathy and 8 age-matched, male diabetic subjects without autonomic neuropathy. None of the patients with autonomic neuropathy had more than 11 apneic episodes per night, and there were no significant differences between the two groups in the number of sleep apneas, the duration of individual apneic episodes, the total duration of irregular breathing during sleep, or the duration and quality of sleep. The arterial oxygen saturation when awake and the lowest arterial oxygen saturation during sleep were also similar in both groups. Thus, diabetic patients with severe autonomic neuropathy have normal breathing patterns and oxygenation during sleep, and it is unlikely that sleep apnea causes these unexpected deaths.

Adult↗