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Biomedical subjects

J C Hogg

Publications and source records attributed to J C Hogg.

At least 19 recordsLinked to original sources
PubMed1979

The pathophysiology of asthma.

Because postmortem studies of humans provide little information on the initial pathophysiologic events in asthma, animal models have been developed. Recently the Ascaris-allergic rhesus monkey has provided an opportunity to examine the onset of pathophysiologic changes following challenge and to correlate them with airway structure. These studies have suggested that the initial interaction between antigen and mast cells may occur in the bronchial lumen or in the epithelium superficial to the tight junctions, where a small but significant percentage of airway mast cells exist. It also appears that this initial antigen-antibody interaction results in the release of mediators that both stimulate the rapidly adapting stretch receptors in the mucosa and alter the mucosal barrier so that proteins of large molecular weight can penetrate. The fact that antigen challenge results in hyperresponsiveness to a subsequent dose of inhaled histamine and increased systemic absorption of histamine suggests that the airway hyperresponsiveness could be related to increased penetration of histamine into the bronchial wall. These observations suggest that the initial event in an acute asthmatic attack is the release of mediators from superficial mast cells, and that this amplifies the allergic response by altering the mucosal permeability so that more antigen reaches the submucosal mast cells. This altered permeability may also help explain the hyperreactivity of the airways to nonspecific airway stimulants in persons with asthma.

Airway Resistance↗
PubMed1979

Relationship between airway hyperreactivity and hyperpermeability in Ascaris-sensitive monkeys.

In four Ascaris-sensitive rhesus monkeys, we measured the fractional absorption of 3H-histamine (3HH) and airway response, as pulmonary resistance (R1), to standard histamine aerosols containing tracer amounts of 3HH for control runs (Run 1) and runs after Ascaris antigen challenge (Run 2). The mean rate of accumulation of radioactivity in the plasma volume as a function of delivered dose during histamine exposure (2 min) was fivefold greater for Run 2 (0.047% delivered dose/min) as compared with Run 1 (0.009% delivered dose/min). Whereas histamine inhalation led to insignificant (less than 25%) increases in R1 over control in Run 1. R1 increased by 247% over control after histamine inhalation in Run 2. Thus, both airway hyperpermeability and hyperreactivity to inhaled histamine were observed following specific antigen challenge in this animal model. These data are consistent with the hypothesis that airway mucosal hyperpermeability induced by an allergic reaction is one of the factors contributing to airway hyperreactivity by increasing flows of inhaled bronchoactive agents to effector sites in the airway wall.

Airway Resistance↗
PubMed1979

Pulmonary effects of acute and chronic antigen exposure of immunized guinea pigs.

Subdivisions of lung volume and pressure-volume (PV) curves of the lung and chest wall were measured in guinea pigs immunized to ovalbumin before and after acute (group 1) and chronic (group 2) antigen exposure. The histopathology produced in chronically exposed animals was also assessed. Animals were anesthetized with pentobarbital sodium and studied in a pressure-sensitive body plethysmograph, using a fluid-filled esophageal catheter to measure transpulmonary pressure (PL). Functional residual capacity (FRC) was determined by the Boyle's law technique; total lung capacity (TLC) was defined as the lung volume at a PL of 30 cmH20, and residual volume (RV) was defined as the lung volume at a transrespiratory pressure of -50 cmH2O. Acute antigen challenge of group 1 animals resulted in a decrease in TLC (22%), and increases in FRC (20%) and RV (110%), suggesting combined bronchoconstriction and alveolar duct constriction. Chronic antigen exposure of group 2 animals resulted in minimal changes in subdivisions of lung volume and PV curves, and produced a histological lesion resembling allergic alveolitis rather than asthma.

Aerosols↗
PubMed1979

The number and distribution of mast cells in monkey lungs.

We estimated the number of mast cells in monkey lungs by both quantitative histologic examination and measurement of total lung histamine, and showed that monkey lungs contain between 10(7) and 10(8) mast cells, with approximately 83% of these being located in conducting airways, and 17% in the parenchyma. The number of mast cells found in each airway generation increased from approximately 60,000 in the trachea to 8 million in the terminal bronchioles. In airways from different generations the number of mast cells superficial to the basement membrane in the epithelium and lumen (EMC) was compared to the number of mast cells found in the submucosa between basement membrane and cartilage and to the number of those found outside the cartilage. The number of EMC varied between animals and ranged from 0-0.4% of the total number of mast cells in the trachea, to 0-27% of the total in the terminal bronchioles. On the average, EMC accounted for 12% of the total number of mast cells in conducting airways, where we calculate that there is approximately one EMC for every 100,000 epithelial cells. Eosinophils were distributed in close relation to mast cells in the mucosa and submucosa, but were rare outside the cartilage. We conclude that the number of mast cells increases from central to peripheral airways and that this may account for the marked peripheral airway response observed after antigen challenge.

Animals↗
PubMed1979

Airway sensitivity to slow-reacting substance of anaphylaxis, histamine, and antigen in Ascaris sensitive monkeys.

The effects of Ascaris suum antigen, histamine, and slow-reacting substance of anaphylaxis (SRS-A) on the respiratory system were compared in 3 anesthetized rhesus monkeys. The agents were administered by instillation into the trachea, and the animals were studied in a volume displacement body plethysmograph. Two of the animals showed skin and bronchial sensitivity to Ascaris suum antigen and responded to it with increased pulmonary resistance and decreased dynamic compliance. A similar response was seen in all 3 animals after instillation of histamine, but SRS-A at 2 concentrations produced a predominant effect of decreased dynamic compliance with lesser alterations in pulmonary resistance. The effects of SRS-A were slow in onset and prolonged, as compared to the abrupt and short-lived effects of Ascaris suum antigen and histamine. The predominant effect of SRS-A on dynamic compliance suggests a more peripheral site of action of this mediator. In 5 monkeys allergic to Ascaris, no SRS-A could be detected in the blood at one and 5 min after antigen challenge, using the bioassay techniques.

Administration, Topical↗
PubMed1979

Bronchial mucosal permeability.

The tracheobronchial epithelium has well-developed tight junctions which on a morphologic basis should be markedly resistant to penetration by protein molecules. Despite this, antigen inhalation in monkeys allergic to Ascaris suum results in the rapid onset of pulmonary physiologic changes. Recent studies in man and animals have shown that a substantial number of mast cells exist in the bronchial lumen and epithelium. We suggest that antigen-antibody interaction initially occurs on these superficial mast cells leading to mediator release and the stimulation of airway irritant receptors. Antigen challenge also results in increased epithelial permeability to protein in the Ascaris-allergic monkey, and from studies on guinea pigs we suggest that this is due to alterations in the tight junctions. Antigen challenge in the monkey also produces increased permeability to labeled histamine and hyperresponsiveness to low concentrations of histamine. We suggest that the apparent airway hyperreactivity to inhaled histamine seen after inhalation of ozone, and NO2, or after upper respiratory infections could be due to damage to epithelial tight junctions. The resultant increase in mucosal permeability would result in an increased amount of histamine reaching airway smooth muscle for a given inhaled concentration.

Airway Resistance↗
PubMed1979

Pulmonary 'mainline' granulomatosis: talcosis of intravenous methadone abuse.

Seventeen intravenous abusers of methadone underwent clinical, roentgenologic and physiologic assessment. Two complained of dyspnea on exertion and two had cor pulmonale. Of 15 patients whose fundi were examined, nine had talc particles in their retinal vessels. The chest roentgenograms of seven showed a diffuse pin-point micronodular pattern and two of the seven also manifested volume loss, one with coalescence of opacities simulating progressive massive fibrosis. Twelve patients had some degree of pulmonary dysfunction, 10 with lowered steady state diffusing capacity and 11 with decreased flow rates (FEV1 and MMF). There was no hyperinflation, but two showed an increase in residual volume. Corticosteroid therapy was attempted on two and was ineffective. Necropsy on the one patient who died revealed severe pulmonary fibrosis and talc granulomas in lungs, liver, kidneys and lymph nodes.

Adult↗
PubMed1978

The relations between structural changes in small airways and pulmonary-function tests.

To examine the relation between small-airways abnormalities and specific lung functions, we performed pulmonary-function tests in 36 patients, of whom two were nonsmokers, one to three days before open-lung biopsy for localized pulmonary lesions. The primary lesion in the small airways was a progressive inflammatory reaction leading to fibrosis with connective-tissue deposition in the airway walls. Increase in disease in small airways correlated with deterioration in lung function. Lesions could be reliably detected (P less than 0.05) by tests for closing capacity, the volume at which air and helium flow ere equal (a test of airway caliber and elastic recoil), and the slope of phase III of the single-breath washout curve (which tests evenness of ventilation). These tests showed abnormalities at a time when the pathologic changes were still potentially reversible and when other tests were not appreciably changed.

Adult↗
PubMed1978

Static lung mechanics of intact and excised rhesus monkey lungs and lobes.

Subdivisions of lung volume and pressure-volume (PV) curves of the lung and chest wall (CW) were measured in 12 rhesus monkeys (Macacca mulatta) under pentobarbital anesthesia. In addition, volumes and PV curves were obtained on the excised lungs and lobes of 12 cynomolgus monkeys (M. fasicularis). Boyle's law was used to determine functional residual capacity (FRC) in the intact animals and water displacement to determine minimal volume (MV) in the excised lungs. Total lung capacity (TLC = lung volume at a transpulmonary pressure of 30 cmH2O) was similar in vivo and in vitro (90 + 83 ml/kg) but residual volume (RV = volume at airway pressure of -50 cmH2O) and MV differed markedly (16.5 + 5.9 ml/kg). In the intact animals a very stiff CW appeared to determine RV, whereas airway closure determined MV in excised lungs. PV curves of upper and lower lobes were not different when expressed as %TLC but when expressed as milliliters of gas per gram of lung, the upper lobes contained significantly more gas per unit weight.

Animals↗
PubMed1978

Pulmonary capillary and permeability during hemorrhagic shock.

In previous experiments from this laboratory horseradish peroxidase was used to study the structural and functional characteristics of the normal canine pulmonary capillary membrane. The present study used the same technique to try to determine if any change occurred in the pulmonary capillary as a result of hemorrhagic shock. We found that hemorrhagic shock caused a fall (5 expt) or no change (2 expt) in estimated pulmonary transcapillary pressure based on Starling's equation. However, lymphatic flow from the lungs increased. Estimated of filtration coefficients showed a highly significant increase (P less than 0.01) during the hypotensive period. Pulmonary lymphatic protein concentrations were not altered, indicating that water and protein continued to traverse the membrane in the same proportions as under normotensive conditions. These data are consistent with recent observations of minimal changes in the intercellular junctions of the capillary endothelium following hemorrhagic shock made independently on lung tissue from these experiments.

Animals↗
PubMed1978

Airway responses to histamine and methocholine in Ascaris suum-allergic rhesus monkeys.

We performed dose-response curves to inhaled histamine (H) and methacholine (MC) in a group of eight rhesus monkeys, with and without natural allergy to Ascaris suum antigen (AA). The animals were anesthetized with pentobarbital sodium, 25 mg/kg im and studied in a volume-displacement body plethysmograph. The dose of H or MC producing a 50% increase in pulmonary resistance (RL) was used to determine sensitivity to these agents and the increase in RL at a given dose was employed as a measure of reactivity. Sensitivity and reactivity to H and MC were then compared with AA responsiveness. A wide range of responses was observed but allergic animals were not more sensitive or reactive to H or MC than nonallergic animals. In addition, we studied the changes in breathing pattern that occurred during the inhalation of AA, H, and MC in four AA-sensitive animals. AA and H produced rapid shallow breathing within 30 s of starting inhalation, but MC, despite causing an equal degree of bronchoconstriction, did not produce alterations in breathing pattern.

Aerosols↗
PubMed1978

Effect of histamine and methacholine on guinea pig tracheal permeability to HRP.

The effects of histamine, methacholine, and ether on the permeability of the respiratory mucosa to macromolecules were investigated employing a radioimmunoassay and histochemical techniques to monitor movement of horseradish peroxidase (HRP) from airway lumen to blood. We found that 0.08% of the dose of HRP instilled into guinea pig tracheas was present in the blood volume at 10 min, and plasma HRP levels increased at a rate of 0.0036% instilled dose/min thereafter. After inhalation challenge, significant increases in plasma rates of accumulation of HRP were recorded for the histamine, methacholine, and ether groups, whereas no change in rate was noted for the control (Tyrode's) group. Electron micrographs of tracheal sections showed HRP penetration into the intercellular spaces of the epithelium after histamine, methacoline, or ether exposure but no penetration in the Tyrode's group. We conclude that, like ether, histamine and methacholine increase tracheobronchial permeability and this effect is most likely mediated by a functional change in the epithelial tight junction.

Aerosols↗
PubMed1978

Pulmonary arterial wedge pressure in hemorrhagic shock.

To test the hypothesis that the position of a pulmonary arterial wedge catheter might affect its ability to measure left atrial pressure, we inserted 2 wedge catheters, one superiorly, and one dependently, in supine dogs. The position of the catheter tips and the zero level of the transducers were located on a lateral chest radiograph so that by referencing the transducers to the posterior surface of the lung and measuring the height of the catheter tip above that reference point, the zones in which the catheter tips were located were determined. When both catheters were in Zone III (pulmonary arterial pressure greater than left atrial pressure greater than alveolar pressure), the wedge pressures accurately reflected left atrial pressure. However, during hemorrhage, left atrial pressure decreased, and when the pulmonary arterial wedge catheter placed superiorly came under Zone II conditions (pulmonary arterial pressure greater than alveolar pressure greater than left atrial pressure), it recorded a constant pressure somewhat greater than left atrial pressure; the pulmonary arterial wedge catheter placed dependently, which remained in Zone III, continued to reflect left atrial pressure. We conclude that a pulmonary arterial wedge catheter measures left atrial pressure only when it is located in Zone III.

Animals↗
PubMed1978

Bronchial asthma.

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Airway Resistance↗