Characterisation of sol and gel phases of infected and mucoid sputum samples from a chronic bronchitic patient.
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Amino Acids↗
Biomedical subjects
L M Reid
Publications and source records attributed to L M Reid.
Crotalaria-induced pulmonary hypertension. Uptake of 3H-thymidine by the cells of the pulmonary circulation and alveolar walls.
Feeding with Crotalaria spectabilis seeds induces structural changes in the pulmonary arterial circulation characteristic of pulmonary hypertension: increased medial and adventitial thickness, the appearance of muscle in smaller arteries than normal, and reduction in the number of peripheral arteries. By autoradiographic techniques, after injection of 3H-thymidine into rats fed Crotalaria for 3, 7, 14, 21, 28, or 35 days, the contribution of hyperplasia to these changes has been assessed at two levels of the pulmonary artery--the hilum and the periphery. In the hilar pulmonary artery, a biphasic increase in labeling index (LI) is seen in each cell type. After 3 days of feeding, the medial smooth muscle cells show a slight but significant increase (1.5 times the control value), and, after 7 days, so do the adventitial fibroblasts (3 x) and the endothelial cells (EC) (2 x). After 14 days LI for all three cell types is again at control values, but after 21 days (wall thickness is no increased) each cell type shows at least a fivefold increase; by 35 days all are again near control levels. In the intra-acinar region, by 14 days, "newly" muscularized arteries are identified and increase in number and proportion up to 35 days; 3H-thymidine uptake is not evident in this cell type until 35 days have passed. The ECs of these arteries, however, show a striking increase in LI after 14 days as do those of the alveolar capillaries. The ECs of the intra-acinar veins show a biphasic response being increased after 7, 28, and 35 days. The present study has shown that Crotalaria ingestion induces hyperplasia and hypertrophy of pulmonary arterial cells at pre- and intra-acinar levels. The early increase in LI probably represents a response to the original cell injury, the later changes, a response to continuing damage or, in part, adaptation to the pulmonary hypertension now present.
Animals↗
The effect of tobacco smoke, with or without phenylmethyloxadiazole (PMO), on rat bronchial epithelium: a light and electron microscopic study.
The effect of whole cigarette smoke on rat airway epithelium and of the addition of an anti-inflammatory drug, phenylmethyloxadiazole (PMO), to the tobacco, was studied in experiments extending up to 6 weeks. Two airway levels were studied, the left main extrapulmonary bronchus and a distal intrapulmonary bronchiolus. After cigarette smoke alone, the greatest change was found in the main extrapulmonary bronchus where there was an increase in epithelial thickness due to cell hypertrophy and a change in cell shape. The number of cells increased in proportion to the duration of exposure. Hyperplasia was not preceded by epithelial degeneration or necrosis. In the animals exposed to tobacco smoke alone, ciliated, mucous and basal cells increased whilst intermediate and epithelial serous cells decreased in number. The appearance of cells intermediate in structure suggests that epithelial serous cells transformed into mucous cells. The change involved an increase in secretory granule size, number and electron-lucency, the last probably reflecting a chemical alteration in the glycoprotein. In ciliated cells, mitochondria increased in length. The concentration of dividing cells increased, notably at days 1 and 7. Addition of PMO to the tobacco, 2 per cent. by weight, diminished the increase in bronchial epithelial thickness, cell size, mucous cell number and percentage of dividing cells seen after tobacco smoke alone: the shift in proportion of the various cell types was similar except that the increase in ciliated cell number was much greater than the increase seen with tobacco smoke alone.
Animals↗
The structural basis of persistent pulmonary hypertension of the newborn infant.
Six neonates of 35 to 42 weeks' gestation had findings of persistent pulmonary hypertension and died between one and 6 days of age despite intensive medical therapy. Each patient had pulmonary artery pressure near or above systemic level, with a right-to-left shunt via the foramen ovale and/or ductus arteriosus. At postmortem, morphometric analysis of the peripheral pulmonary vascular bed revealed extension of muscle into small arteries, which was severe in five of six patients; all alveolar duct and wall arteries (less than 30 micrometers external diameter), normally nonmuscular, were fully muscularized. In these five patients medial wall thickness of the normally muscular intra-acinar arteries was doubled; arterial size and number, however, were normal in all. This striking structural maldevelopment of the peripheral pulmonary arterial bed occurred or was initiated in utero and does not merely represent a failure of the fetal pattern to regress. We suggest that this particular group of patients remained refractory to all current modes of therapy because of these severe structural pulmonary vascular changes.
Humans↗
Influence of anti-mouse interferon serum on the growth and metastasis of tumor cells persistently infected with virus and of human prostatic tumors in athymic nude mice.
Baby hamster kidney or HeLa cells form tumors in 100% of athymic nude mice. When such cells are persistently infected (PI) with RNA viruses, such as mumps or measles virus, the tumor cells either fail to grow or form circumscribed benign nodules. Neither the parental nor the virus PI tumor cells form invasive or metastatic lesions in nude mice. Previous studies have indicated a correlation between the susceptibility of virus-PI tumor cells in vitro and the cytolytic activity of natural killer (NK) cells and their failure to grow in vivo. Because interferon (IF) is the principal regulatory molecule governing the differentiation of NK cells, it was possible to test the relevance of the IF-NK cell system in vivo to restriction of tumor growth by treatment of nude mice with anti-IF globulin. This treatment was shown to reduce both IF production and NK activity in spleen cells. Both parental and virus-PI tumor cells grew and formed larger tumors in nude mice treated with anti-IF globulin than in control nude mice. The viral-PI tumor cells and the uninfected parental cells formed tumors in treated mice that were highly invasive and often metastatic. Some human tumor types have been notoriously difficult to establish as tumor lines in nude mice (e.g., primary human prostatic carcinomas). When transplanted into nude mice treated either with anti-IF globulin or anti-lymphocyte serum, two prostatic carcinomas grew and produced neoplasms with local invasiveness and some metastases. The results are consistent with the view that interferon may be important in restricting the growth, invasiveness, and metastases of tumor cells by acting indirectly through components of the immune system, such as NK cells.
Animals↗
Inhibition by vasoactive intestinal peptide of glycoconjugate and lysozyme secretion by human airways in vitro.
The effects of vasoactive intestinal peptide (VIP) were analyzed on the in vitro release of radioactively labeled mucus glycoconjugates and lysozyme by explants of human bronchial mucosa from normal subjects and from patients with chronic bronchitis. These effects were compared with the effects of VIP on the discharge of labeled macromolecules (analyzed by quantitative autoradiography) from mucous and serous cells of the airway submucosal glands. In explants of 9 mucosal specimens of normal airways, VIP (10 ng to 1 micrograms/ml) caused a dose-dependent inhibition of baseline and methacholine-stimulated release of both glycoconjugates and lysozyme. At a concentration (1 micrograms/ml) that caused maximal inhibition of glycoconjugate and lysozyme release, VIP also caused a small inhibition of baseline but not methacholine-induced discharge of labeled macromolecules from mucous and serous cells of the submucosal glands. In explants from 5 patients with chronic bronchitis, VIP did not inhibit baseline or methacholine-stimulated glycoconjugate release and mucous or serous cell discharge, even at doses greater than 1 micrograms/ml. By contrast, VIP did inhibit baseline and methacholine-stimulated release of lysozyme, but this was less marked than in explants of normal airways. In view of the proximity of neurons containing VIP to submucosal gland cells, this study supported the hypothesis that VIP may contribute to the neurohumoral regulation of mucus secretion by the human airway. It was evident, however, that the effects of VIP could not be accounted for in terms of inhibiting cell discharge alone. In chronic bronchitis, the reduction or absence of sensitivity to VIP inhibition suggests a functional difference in the regulation of mucus secretion, which may contribute to mucus hypersecretion.
Bronchi↗
Tumorigenicity in nude mice of a human hepatoma cell line containing hepatitis B virus DNA.
The human hepatocellular carcinoma cell line PLC/PRF/5, which synthesizes and secretes hepatitis B surface antigen, was grown under optimal conditions in tissue culture, using Eagle's minimal essential medium supplemented with 10% fetal bovine serum and 10(-11) M triiodothyronine on collagen rafts. Injection s.c. of the PLC/PRF/5 cell line into athymic BALB/c nude mice resulted in the growth of a well-circumscribed, moderately differentiated hepatocellular carcinoma. The intervals until tumor appearance and tumor "take" rates were dependent on inoculum dose. Four to 5 x 10(6) cells induced tumor growth in 29% of 14 injected mice within 29 to 40 days, while 7 to 13 X 10(6) cells induced tumors in all 15 mice within 10 to 12 days after inoculation. Hepatitis B surface antigen was detected in the nude mouse serum and tumor tissue, and its concentration roughly correlated with tumor weight. A low level of antibody against hepatitis B surface antigen was detected in five tumor-bearing animals, as well as in one mouse which did not produce a tumor. Hepatitis B core antigen and its antibody and hepatitis B e antigen and its antibody were not detected in 26 mice, using immunohistochemical and radioimmunoassay methods. alpha-Fetoprotein, carcinoembryonic antigen, and alpha-antitrypsin were detected in nude mice tumors, using the peroxidase-antiperoxidase technique. Finally, hepatitis B virus DNA, identified in the nude mouse tumor by molecular hybridization techniques, was compared to PLC/PRF/5 cell line hepatitis B virus DNA.
Animals↗
Enhanced tumorigenicity and hepatitis B virus genes in a human hepatoma cell line injected into immunosuppressed nude mice.
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Animals↗
Quantitative structural analysis of the pulmonary vascular bed in congenital heart defects.
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Adolescent↗
Pulmonary hypoplasia resulting from phrenic nerve agenesis and diaphragmatic amyoplasia.
We report the clinical, general postmortem, and pulmonary morphometric features of a unique case of pulmonary hypoplasia resulting from phrenic nerve agenesis and diaphragmatic amyoplasia. The lungs showed a marked reduction in the number of bronchial branches with relatively normal intra-acinar growth, indicating interference with lung development before the sixteenth week of gestation. The pulmonary abnormalities arose early in gestation, suggesting that normal diaphragmatic neuromuscular development is essential for maintaining thoracic volume and permitting lung growth even before the fetus is capable of regular respiratory movements. The infant also had remodeling of the pulmonary circulation, causing persistent pulmonary hypertension. This case clarifies the interrelationship of diaphragmatic innervation, thoracic volume, fetal respiration, and lung development.
Abnormalities, Multiple↗
Connective tissue biomatrix: its isolation and utilization for long-term cultures of normal rat hepatocytes.
A new procedure is introduced for the isolation of connective tissue fibers, called biomatrix, containing a significant portion of the extracellular matrix (basement membrane components and components of the ground substance). Biomatrix isolated from normal rat liver contains >90% of the tissue's collagens and all of the known collagen types, including types I and III and basement membrane collagens. The purified collagenous fibers are associated with noncollagenous acidic proteins (including fibronectins and possibly small amounts of glycosaminoglycans). Procedures are also described for preparing tissue culture substrates with these fibers by either smearing tissue culture dishes with frozen sections or by shredding the biomatrix into small fibrils with a homogenizer. The biomatrix as a substrate has a remarkable ability to sustain normal rat hepatocytes long-term in culture. The hepatocytes, which on tissue culture plastic or on type I collagen gels do not survive more than a few weeks, have been maintained for more than 5 mo in vitro when cultured on biomatrix. These cells cultured on rat liver biomatrix show increased attachment and survival efficiencies, long-term survival (months) and retention of some hepatocyte-specific functions.
Animals↗
Long-term cultures of normal rat hepatocytes on liver biomatrix.
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Animals↗
Prematurity, hypoplasia of the pulmonary vascular bed, and hypertension: fatal outcome in a ten-month-old infant.
The present report describes an infant weighing 610 g who did not develop respiratory distress at birth, but who failed to thrive, and died at 10 months of age with suprasystemic pulmonary hypertension of unknown cause. Morphometric analysis of the lung, including the pulmonary artery circulation and serial reconstruction of several arterial pathways, revealed hypoplastic arteries both for age and lung size, and also arterial dilatation lesions and interpulmonary artery anastomoses. Pulmonary hypertension of this degree, which is noncardiac in origin, has not been reported before in a premature infant within the first year of life.
Arteries↗
Mucous membrane of respiratory epithelium.
Of the eight epithelial cell types of the airway surface epithelium three are secretory, the mucous, serous and Clara cells: the first two are also found in the submucosal glands. Organ culture results indicate that the pattern of control of the surface cells is different from that of the glands. Our recent studies show that in the surface epithelium Clara and serous cells can quickly convert to mucous as do nonsecretory undifferentiated cells. The balance between the various cell types changes with airway level. The type of glycoprotein within the secretory granules is neutral or acid, sialylated or sulfated, and also shows a regional pattern. Homeostasis is maintained in the normal but the equilibrium is quickly upset by a variety of irritants, infection of drugs. Change in pattern of glycoprotein synthesis depends largely on change of granules. The granules at the cell apex change first. The nature and distribution of the various receptor binding sites is significant in patterns of control. This lability occurs in an intact epithelium and whether or not mitotic activity is increased. With irritation tolerance to stimulus develops. Antiinflammatory agents can protect against some of these cellular and intracellular events. Our organ culture studies and biochemical analysis of secretion complement the tissue studies. Recent studies show that isoproterenol and salbutamol (a nonselective beta agonist and a selective beta 2, respectively) alter the normal mix of cell types and quickly, but that they have different regional specificity.
Adrenergic beta-Agonists↗
Growth of human breast carcinomas in nude mice and subsequent establishment in tissue culture.
Thirty-two malignant human breast tumors were implanted s.c. in female nude mice. Seven tumors survived for two passages, and four were established into permanent transplantable tumor lines. The transplantable tumors have retained the histopathology of the original tumor throughout passaging in the nude mice. In addition, two of the transplantable tumors have low concentrations of estrogen receptor. Tissue culture of the original tumor specimens upon receipt resulted in epithelial outgrowth in 15 of 32 primary cultures. However, no permanent cell lines were established. Attempts to culture 23 tumors frozen with dimethyl sulfoxide upon receipt were unsuccessful. In contrast, establishment of cell strains was successful with tumor specimens cultured following passage in the nude mice; three cell strains were initiated from two of the transplantable tumors.
Adenocarcinoma↗
Needs for animal models of human diseases of the respiratory system.
Animal models are of two types those that occur spontaneously and those that the scientist produces by artefact. One value of spontaneously occurring models is that if pathogenetic mechanisms are identified, they give new leads for the study of human disease. There is a need for spontaneously occurring examples of so-called primary or idiopathic pulmonary fibrosis, pulmonary hypertension (arterial or venous), and emphysema. Acquired or artefactual models of each of these conditions are available and have led to better understanding of the pathological changes, but they have not led to identification of the basic or primary abnormality. A naturally occurring model of cystic fibrosis could be a major event in our control of this disease. A spontaneously occurring form of asthma is needed as a bridge between experiment and patient. Artefactual models that are needed are of bronchopulmonary dysplasia and shock lung. There is probably enough agreement--but only just--on the nature of bronchopulmonary dysplasia for specific needs to be identified. Here the questions concern the choice of an appropriate species--or several--in which to study the premature lung and its adaptation to air breathing and supportive therapy. Knowledge of comparative anatomy and physiology must influence choice of species for certain models. For adult respiratory failure, or shock lung, a model is needed that progresses to pulmonary hypertension. Spontaneous models of interstitial pneumonia and of infection, both viral and bacterial, are needed. An animal model of a disease is only as useful as the questions we ask of it.
Animals↗
Early pulmonary vascular changes in congenital heart disease studied in biopsy tissue.
Patients with congenital heart defects who had or were at risk for developing pulmonary artery hypertension underwent lung biopsy at the time of intracardiac repair. In 95 consecutive patients with either ventricular septal defect, d-transposition of the great arteries, or a defect of the atrioventricular canal, the pulmonary arteries were evaluated microscopically by quantitative morphologic techniques, and the findings were correlated with hemodynamic data obtained at a recent preoperative cardiac catheterization. Three grades of severity of early pulmonary vascular changes were identified, which correlated with hemodynamic evidence of progressive functional impairment. Grade A denotes cases with abnormal extension of muscle into peripheral arteries only; pulmonary blood flow is increased but pulmonary artery pressure is normal. In grade B an increased medial wall thickness of the normally muscular arteries is also present, and in these cases pulmonary artery pressure is also increased. Grade C denotes cases in which in addition to the findings in grade B disease there is a reduction in the number of small peripheral arteries; in these cases pulmonary vascular resistance is increased. Follow-up postoperative hemodynamic evaluation will reveal the significance of these changes in reflecting irreversible functional impairment of the pulmonary vascular bed.
Adolescent↗
Mechanism of rejection of virus persistently infected tumor cells by athymic nude mice.
Cell lines known to be tumorigenic in the nude mouse were modified by rendering them persistently infected (P.I.) with a variety of RNA viruses, including measles, mumps, vesicular stomatitis virus, and influenza. Although as few as 100 HeLa or BHK cells produced tumors in 100% of nude mice, as many as 2 x 10(7) of the same cells P.I. with viruses failed to produce tumors. An active host response responsible for restricting the growth of the P.I. cells was suggested by the findings of marked mononuclear cell infiltrates at the inoculation sites and the inability of irradiated nude mice to reject them. An analysis of the in vitro cytotoxic activity of spleen cells from normal nude mice indicated that: (a) P.I. cell lines, but not uninfected cell lines, were susceptible to spontaneous cytotoxicity; (b) in vivo inoculation of P.I. lines induced an enhanced cytotoxic activity for P.I. targets in vitro, and this induction was not specific either for inducing virus or cell line; and (c) the effector cell had the characteristics for natural killer (NK) cells. Although the specificity of recognition of the various P.I. cell lines remains unclear, cold competition experiments indicated that blocking the killing of one P.I. cell line, e.g. HeLa-measles, could be achieved only by unlabeled homologous cells, i.e. HeLa-measles, and not by uninfected cells or other P.I. lines. A variant subline of BHK cells P.I. with VSV was selected for its ability to withstand the rejection process in nude mice. These cells formed metastatic and invasive tumors in nude mice. Although they were the most potent inducers in vivo of NK cell activity against various P.I. targets, they were the most resistant of the P.I. lines to NK cell cytotoxicity in vitro. In this system there was a good correlation between tumor rejection in vivo and susceptibility to NK cells in vitro. The present results suggest that NK cells may play a significant role in both rejection of tumor cells, and in resistance to viruses, particularly persistent infections.
Animals↗