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Biomedical subjects

L Reid

Publications and source records attributed to L Reid.

At least 73 records · Page 4Linked to original sources

Compression of intrapulmonary bronchi by abnormally branching pulmonary arteries associated with absent pulmonary valves.

In 3 patients with absent pulmonary valve syndrome and absent ductus arteriosus, the lungs were injected and analyzed postmortem using morphometric techniques. Two patients had tetralogy of Fallot and 1 had D-transposition of the great arteries, the latter being the first autopsy-proved case of absent pulmonary valve with transposition. In addition to the expected dilatation of the central pulmonary arteries and compression of the mainstem bronchi, postmortem pulmonary arteriography revealed a bizarre pattern of hilar branching. Instead of single segmental arteries, tufts of arteries arose which entwined and compressed the intrapulmonary bronchi. In all 3 patients the histologic structure of the pulmonary arteries was abnormal. The elastic lamina of the media of the right and left pulmonary arteries were increased in number outside the lung, but were decreased within the lung. At both sites, the elastic laminae were thickened and fragmented. In the 2 ventilator-dependent patients, there was slight medial hypertrophy and extension of muscle into normally nonmuscular arteries. In 1 of the 2 cases in which the number of bronchial generations was counted, they were decreased, and in the 1 case in which bronchial count was unknown, alveolar multiplication was severely impaired. Therefore, our data may explain why, in some patients with absent pulmonary valve syndrome, relief of compression of the mainstem bronchi alone does not appreciably alleviate or reverse severe respiratory disease.

Bronchi↗

Pulmonary veno-occlusive disease in siblings: case reports and morphometric study.

Two cases of fatal veno-occlusive disease are described: the first in a boy 14 years old and the second in his sister, who died, at age 13, only a few months later. In both, the first symptom was effort-induced dyspnea and the course of the disease was rapid. The chest radiograph of the boy showed diffuse opacities, whereas that of the girl showed Kerley lines bilaterally. In both, at autopsy, a diagnosis of severe veno-occlusive disease was confirmed, with partial or complete occlusion of much of the pulmonary venous bed by organized thrombi. The pulmonary vascular system of the girl was processed for light microscopic morphometry by injection of radiopaque medium into the veins of one lung and the arteries of the other. Although there was little filling of the venous system, much of the arterial system filled down to the capillary level. Pre-acinar and intra-acinar arteries showed medial hypertrophy and extension of smooth muscle into precapillary arteries. The concentration of patent intra-acinar arteries relative to alveoli was not significantly less than normal, whereas the concentration of veins was strikingly reduced. Possible pathogenetic mechanisms are discussed.

Adult↗

Response of the pulmonary circulation to acute hypoxia in the growing pig.

In a previous article we have analyzed the structure of the growing pig lung and correlated the findings with cardiorespiratory function studies on the same animals (J. Appl. Physiol: Respirat. Environ. Exercise Physiol. 45: 806-817, 1978). The present study analyzes the pulmonary and systemic vascular responses to acute hypoxia in some of those animals at three ages, 2-4, 5-8, and 9-12 wk, the lung of the 12-wk-old pig being structurally similar to that of the adult. In all anesthetized animals, acute hypoxia (5 min 10% fractional inspired oxygen concentration) increased mean pulmonary arterial pressure (Ppa) and total pulmonary resistance (TPR). The increase over base line of Ppa was 41.3% in animals aged 2-4 wk; 83.0% in those aged 5-8 wk, and 136.9% in those aged 9-12 wk; for TPR the increase in the three age groups was 66.4, 92.4, and 138.9%, respectively. This difference in vasoactivity with age is associated with the progressive extension of smooth muscle into the intra-acinar arterial tree, which we have previously shown is an important feature of the structural remodeling that occurs during postnatal lung development in both man and swine.

Acute Disease↗

Structural changes in the canine lung and pulmonary arteries after pneumonectomy.

The study set out to describe the structural changes in the remaining lung of beagle dogs after left-sided pneumonectomy, performed at 6-10 wk or 1 yr of age. After a 5-yr postoperative recovery, lung volume and weight had increased in the operated groups, though only the latter was significant in comparison with 5-yr-old controls. In both operated groups, total alveolar number in the right lung was normal. The total volume of alveolar ducts, mean linear intercept, and (in the young operated group) mean alveolar volume were increased, indicating a compensatory enlargement of distal air spaces. Lobar differences reinforced these conclusions. In the 1-yr operated group, medial hypertrophy was present in preacinar arteries, with a similar trend in intra-acinar arteries where peripheral extension of medial smooth muscle was also present. Despite the lack of structural change in their pulmonary arterial system, the young operated group had right ventricular hypertrophy. Previously reported evidence of alveolar proliferation shortly after pneumonectomy probably represents a speeding up of normal developmental patterns, but after prolonged recovery the final alveolar number is no greater than normal.

Animals↗

Pulmonary arterial and alveolar development in normal postnatal rat lung.

The postnatal development of rat lung was studied by quantitative light microscopic techniques at 12 hours and at 3, 8, 11, 15, 22, and 36 days of age. Particular emphasis was placed on the pulmonary arterial circulation. At birth the lung is not the adult lung in miniature; adaptation occurs through a series of relatively fast steps. A spurt of alveolar multiplication occurs between 3 and 8 days of age, followed, between 8 and 11 days, by one of arterial multiplication. Muscular, partially muscular, and nonmuscular arteries are present within the acinus from birth and their proportion, in each intra-acinar region, is similar at all ages examined except in the alveolar wall where muscular arteries are not found before 11 days of age. Between 12 hours and 8 days, medial thickness of the intra-acinar arteries decreases. At about 15 days of age this decrease is followed, in both pre-acinar and intra-acinar regions, by an increase in medial thickness. Between 12 hours and 3 days, absolute weight of the right ventricle decreases. This pattern of growth indicates that, at certain times, lung development is especially susceptible to injury and, also, that the nature of the disturbance is determined by its timing.

Angiography↗

Pulmonary vascular remodeling in adult respiratory distress syndrome.

To analyze microvascular changes, angiograms and microscopic sections of the lung were prepared from 12 patients dying after severe adult respiratory distress syndrome (ARDS) of diverse cause. Anatomic features of the precapillary arterial bed were morphometrically assessed and related to the duration of acute lung injury. In intra-acinar arteries, medial thickness was increased after short duration ARDS (less than 12 days). Preacinar arteries developed medial thickening only after ARDS of long duration (18-60 days). Mean external diameter (ED) of partially muscular intra-acinar arteries was less than normal in both duration groups, whereas ED of muscular arteries was less in the long duration group. Concentrations of partially and fully muscular arteries tended to be higher in ARDS lungs. These results give evidence of an extension of smooth muscle into normally nonmuscular, smaller pulmonary arteries. Total artery concentration in 7 of the 12 patients was less than the normal, and dilatation of intra-acinar muscular arteries was often observed. The ARDS is characterized by partial or complete disruption and even disappearance of much of the pulmonary vascular bed.

Adult↗

Normal postnatal development of the media of the rat hilar pulmonary artery and its remodeling by chronic hypoxia.

The present morphometric and electron microscopic study follows the development of the hilar intrapulmonary artery of rat form 12 hours to 36 days of age and its structural adaptation to hypobaric hypoxia (380 torr) when exposed for periods of 3, 7, 14, and 28 days starting at 8 days of age. In control animals a striking increase in medial thickness is seen at 11 and 15 days of age and is accompanied, at 11 days, by an increase in the organelles of smooth muscle contraction-the myofilaments-and at 15 days, by an increase in rough sarcoplasmic reticulum. From 15 days, a gradual increase in collagen fibrils and elastin occurs in the extracellular ground substance. With exposure to hypoxia, from day 14 medial thickness increases more than the age-matched controls due to an increase in extracellular ground substance and to thickening of the elastic laminae. At all times studied, smooth muscle diameter is similar to the age-matched controls, but the normal fluctuations in volume density of the contractile elements and the rough sarcoplasmic reticulum are blunted. In the extracellular ground substance, the matrix is increased and collagen fibrils reduced, both in concentration and diameter. Thus, in young hypoxic rats, the narrowed lumen and external diameter of the large muscular arteries is associated with abnormal collagen formation. The hypoxia-induced changes in the young rat are different from those reported in the adult in which medial thickening is the result of increased extracellular ground substance with a normal concentration of collagen fibrils and hypertrophy of the smooth muscle cells. In the young lung, the structural changes have more far-reaching effects than the adult since they also interfere with lung growth.

Aging↗

On the heterogeneity of murine natural killer cells.

The heterogeneity of cells capable exerting spontaneous cytotoxicity in vitro was explored using antisera to several genetically determined surface markers on mouse lymphocytes. Four phenotypes of cells derived either from fresh or cultured murine lymphoid tissue were found to exert natural killer (NK) activity in vitro. One affector cell subset, termed NKI cells, had the serological phenotype of Thy-1-, Lyt-2-, Qa5+, and lysed measles virus persistently infected target cells (HeLa-Ms) but not P815 mastocytoma cells. It corresponds with the NK cells described in most systems in which lymphoma targets are commonly used. A second subset, with the same target cell specificity, termed NKT is a thymus-independent cell with the phenotype Thy-1+, Lyt-2-, Qa-5+, Ly-5+. A third subset of NK cells, termed T killer (TK) cells deriving from cultures of conventional but not nude mouse spleens, mediated spontaneous cytotoxicity of P815 mastocytoma cells, but not of virus-infected targets. It has a phenotype of Thy-1+, Lyt-2+, Qa-5-, Ly-5+, apparently identical with that of conventional, antigen-specific cytotoxic T lymphocytes. The fourth phenotype of NK cells, termed NKM, derived primarily from cultures of bone marrow, is cytotoxic for HeLa-measles but not P815, and expresses only Ly-5+ among the various markers tested. Beige mice possess normal TK and NKM activities, but had normal NKI, NKT as well as NKM activity. All NK cell subsets express the Ly-5 surface marker. The existence of four phenotypically distinct NK effector cells was strengthened by studies on selective regulation of their activity by two different biological factors. Interferon (IFN) augmented NK activity of primarily one of the subsets examined, the NKI cell; the activity of IFN on NKT cells could not be directly tested, but IFN was without positive effect on TK or NKM cells. In contrast, partially purified IFN-free interleuken 2 (IL-2) augmented the activities of both the TK and NKT subsets, but not of NKI or NKM cell. IL-2 was active in augmenting NK activity in spleen cells obtained from both conventional and nu/nu mice, but was without effect on spleens of nu/nu mice depleted of Thy-1+ cells. These and other data suggest that IL-2 acts primarily, if not exclusively, on THy-1+ cells. These results strengthen the view that natural cytotoxicity in vitro can be mediated by several distinct cell populations under different genetic and regulatory control and indicate the importance of defining and delineating the cell lineages of each and the role of the independent subsets in resistance to virus infections and tumors in vivo.

Animals↗

Inhibition of glycoconjugate secretion by colchicine and cytochalasin B. An in vitro study of human airway.

The effects have been analyzed of cytochalasin B and colchicine on the secretion of glycoconjugates by human bronchial explants labeled in vitro with radioactive glucosamine. Both cytochalasin B and colchicine had no effect on baseline 14C-labeled glycoconjugate release but caused a dose-dependent (10(-7)-10(-4) M) inhibition of 14C-glycoconjugate release and discharge of labeled macromolecules from mucous and serous cells induced by 5 X 10(-5) M methacholine. Quantitative autoradiographic analyses showed that neither cytochalasin B nor colchicine inhibited 3H-threonine or 3H-glucosamine incorporation into mucous and serous cells of the submucosal glands or goblet cells of the airway epithelium. Colchicine (10(-5) M) but not cytochalasin B significantly reduced the rate at which labeled macromolecules were transported through mucous, serous and goblet cells but this effect was not observed until 4h after the addition of colchicine. Neither cytochalasin B nor colchicine affected the basal rate of labeled-macromolecule discharge from mucous, serous or goblet cells. At a concentration of 10(-5) M, both agents completely inhibited the increase in labeled-macromolecule discharge induced in mucous and serous cells by methacholine. Our results suggest that in the submucosal gland of human airways microtubules and microfilaments may be important in secretagogue-induced but not in baseline cellular glycoconjugate discharge, implying that the mechanisms of the two processes differ significantly. Furthermore, a role for microtubules is suggested in the transport of secretory granules through mucous, serous and goblet cells.

Aged↗

Lung biopsy with frozen section as a diagnostic aid in patients with congenital heart defects.

In eight patients with congenital heart defects and equivocal preoperative hemodynamic data, lung biopsy with frozen section was performed and quantitative morphometric analysis carried out to help select a palliative or corrective surgical procedure. During catheterization it had been possible in only six of the eight patients to enter the pulmonary artery and obtain pressure measurements; four patients had moderate to severe elevation of pulmonary vascular resistance whereas the other two had only mild elevation of pulmonary arterial pressure, but they were being considered for a Fontan procedure. The lung biopsy tissue was taken inflated and fixed inflated in hot glutaraldehyde. From cryostat sections arterial concentration was assessed relative to alveolar concentration, and the degree of arterial muscularity was assessed by wall thickness and extension of muscle; the more advanced Health-Edwards arterial changes were also evaluated. On the basis of the morphologic assessment, six of the eight patients underwent corrective surgery and two underwent a palliative procedure. Postoperative hemodynamic data available in four of the patients who underwent corrective surgery revealed either a significant reduction in pulmonary vascular resistance or return to a normal level of pulmonary arterial pressure, whereas no change has occurred in the one patient studied who underwent a palliative procedure. Assessment of pulmonary arterial development and structure on lung biopsy with frozen section proved helpful in deciding between a palliative and corrective surgical procedure.

Adolescent↗

Age and sex influence on pulmonary hypertension of chronic hypoxia and on recovery.

To study the influence of age and sex on the hemodynamic and structural response of the pulmonary vascular bed to chronic hypobaric hypoxia, "infant" Sprague-Dawley rats from 8 days old and "adult" rats from 9 wk old, each group including both sexes, were exposed to half atmospheric pressure for 1 mo and then allowed to recover in room air for up to 3 mo. During hypoxic exposure, pulmonary artery hypertension (Ppa) developed in all groups. The level of Ppa was similar in both male and female infant and in male adult rats but was significantly lower (P < 0.01) in the female adult rats. After recovery in room air, only partial regression of Ppa had occurred in all groups (P < 0.001). In male and female adult rats, recovery values were similar but infant rats had more residual Ppa than adults (P < 0.001). The structural changes that developed during hypoxia, especially the abnormal presence of muscle in small and peripheral intra-acinar arteries, were more severe in male adult rats compared with female adults (P < 0.01) and in infants of both sexes compared with male adults (P < 0.01). After recovery, residual structural changes were present in all rat groups but were most severe in the infants (P < 0.01).

Age Factors↗

Airway responsiveness to inhaled mediators: relationship to epithelial thickness and secretory cell number.

Naturally occurring variations in airway responsiveness to inhaled mediators were correlated with various anatomic indexes thought to be related to airway responsiveness. Specifically, the airways of 2 relatively unresponsive and 3 relatively responsive dogs were compared in terms of epithelial thickness, secretory cell number, smooth muscle thickness, and airway mucous gland number and size. More responsive dogs were found to have thinner epithelium and higher secretory cell counts than less responsive dogs. No significant differences between the 2 groups were noted with respect to smooth muscle thickness or mucous gland number and size. Although these observations identify an association between these anatomic features and airway responsiveness, it does not imply a causal relationship.

Airway Resistance↗