Search PubMed⌕ Search

Biomedical subjects

J A Hayes

Publications and source records attributed to J A Hayes.

At least 55 records · Page 3Linked to original sources
PubMed1982

Elastase-induced emphysema: asynchronous bronchial, alveolar and endothelial cell proliferation during the acute response to injury.

This study was undertaken to determine whether elastase injury, which results in extensive remodelling of the hamster lung to produce a panacinar type of emphysema, also induces significant lung cell damage. Anaesthetised hamsters were given a single intratracheal injection of 0.3 mg (18 units) purified elastase (Sigma Type IV) in physiologic saline and were killed 4, 6, 8, 16, 24 h, 2, 4, 8, and 16 days after exposure. DNA synthesis was assessed by autoradiography of sectioned tissue and scintillation counting of tissue blocks using injected tritiated thymidine (3HTdR). DNA, RNA and protein levels were also measured. Saline injected and unexposed animals were used as controls. Widespread mitotic activity was induced in three separate cell compartments, the peak of activity in each compartment occurring at different times. The first peak in labelling index was seen in non-ciliated, non-secretory bronchial cells at 24 h when a value of 8 per cent was reached. This was followed by mitosis in Type II alveolar cells with a labelling index of 15 per cent at 2 days and, lastly, in endothelial cells which showed an index of 9.8 per cent at 4 days. The differences between the peaks was significant (P less than 0.001). RNA content on elastase-exposed animals showed prolonged depression and had not regained control values by the end of the experiment. Protein and DNA content, and 3HTdR incorporation showed significant elevations, particularly about the fourth day after injury. Protein and DNA content and 3HTdR incorporation were not significantly changed in either group of controls.

Animals↗
PubMed1982

Endogenous peroxidase in the conducting airways of hamsters: morphologic evidence of synthesis and secretion.

The lower respiratory tract of the hamster was examined for evidence of endogenous peroxidase activity. Using the standard diaminobenzidine cytochemical technique with controls to distinguish peroxidase from other hemoproteins, brown peroxidase reaction product was observed in the tracheal lumen and within epithelial secretory cells. The lumen and secretory cells of submucosal glands also contained peroxidase activity. Peroxidase-positive cells were most numerous in the upper trachea. Activity gradually decreased distally so that the least number of positive cells occurred in the extrapulmonary bronchus. Older animals contained many more positive cells than did younger animals. Within the lung, all epithelial cell types in both conducting and respiratory zones lacked activity. Peroxidase-positive cells in the tracheo-bronchial epithelium were identified as mucous cells by electron microscopy. Within these cells, peroxidase activity was found in the nuclear envelope, cisternae of rough endoplasmic reticulum, Golgi saccules, condensing vacuoles, and secretory granules. Discharge of the granules into the lumen appeared to result from a merocrine type of secretion. These ultrastructural findings are similar to those described for the secretory peroxidase in mammary and salivary glands. The peroxidase in these glands plays a key role in a nonspecific antibacterial system. Although the function of airway peroxidase is presently unknown, it is quite possible that it too possesses anti-infectious properties, thus forming an important adjunct to the well-known physical, cellular, and immunologic processes that protect the respiratory tract from microbial and toxic injury.

Animals↗
PubMed1981

Ultrastructural localization of endogenous peroxidase in the lower respiratory tract of the guinea pig.

Endogenous peroxidase activity was demonstrated by cytochemistry in mucous cells of the submucosal glands and tracheobronchial epithelium of guinea pigs. It is localized in the nuclear envelope, in cisternae of rough endoplasmic reticulum, and in secretory granules. It was not seen in Golgi saccules or in the airway lumen. By contrast, all epithelial cells within the lung including mucous (goblet) cells lack activity. Reaction product is also absent from alveolar macrophages and mast cells. The appearance of peroxidase in mucous cells is age-related. No activity was seen at 1.5 ms of age. A few mucous cells were positive at 2.5 and 3 ms while the proportion of positive cells increased substantially up to 7 ms. Thus, the age of guinea pigs in HRP transport studies must receive careful consideration in order to avoid misinterpretation of results. The function of mucous cell peroxidase is unknown. The results of this study suggest that it is secreted. Whether it plays a significant role in lung defense through its well documented anti-infectious properties remains to be determined.

Aging↗
PubMed1981

Comparison of transbronchial and open biopsies in chronic infiltrative lung diseases.

To ascertain the diagnostic reliability of transbronchial biopsy (TBB) a prospective comparison with open lung biopsy was made. All patients with undiagnosed diffuse infiltrative (interstitial) lung disease had a TBB. When this was characteristic of tumor, sarcoidosis, or infection, no additional biopsy was deemed necessary. In all other patients, an open biopsy was performed. Between January 1976 and May 1980, among 176 patients with interstitial disease, 60 (34.1%) required lung biopsy. Transbronchial biopsy was contraindicated in 7, leaving 53 in the study group. Among these 53 patients TBB was diagnostic in 20 (37.7%), and the histologic findings in the remaining 33 patients who lacked definitive tissue diagnoses were reported as normal lung, 10 patients; nonspecific abnormalities, 11 patients; interstitial pneumonia, 6; interstitial fibrosis, 3; inadequate specimen, 3. Open biopsy in these 33 patients resulted in specific diagnoses in 92%, and these diagnoses bore little relationship to the original TBB diagnoses. We concluded that TBB diagnoses of interstitial pneumonia, chronic inflammation, nonspecific reaction, and fibrosis are unreliable and often entirely misleading. In this group, an open biopsy is required to reach a specific histologic diagnosis.

Adolescent↗
PubMed1981

Lung lysyl oxidase and prolyl hydroxylase: increases induced by cadmium chloride inhalation and the effect of beta-aminopropionitrile in rats.

Industrial workers who are accidentally exposed to cadmium fumes often develop severe lung damage leading to widespread peribronchiolar scarring. This study examined the effect of a single exposure of cadmium chloride aerosol on rat lung lysyl oxidase and prolyl hydroxylase, both markers of connective tissue biosynthesis. Rats were killed at 2, 4, 7, 10, and 21 days after a 2-h exposure to 0.1% Cdcl2 aerosol. Total lung lysyl oxidase was increased 14.8 times that a saline control animals by 4 days and returned to near normal values by 10 days. Interestingly, a small amount of lysyl oxidase activity was also detectable in the lung lavage of unexposed animals and was markedly elevated at the earlier times after cadmium exposure. Total lung prolyl hydroxylase activity paralleled that of lung lysyl oxidase and increased 7.4-fold by the fourth day. A significant increase in total lung hydroxyproline could be demonstrated. Administration of beta-aminopropionitrile, an irreversible inhibitor of lysyl oxidase, prevented much of the increase in lysyl oxidase activity and the accumulation of collagen. The altered tissue amounts of lysyl oxidase and prolyl hydroxylase after cadmium inhalation correlated well with the marked interstitial cell hyperplasia 4 to 5 days after exposure and suggested that connective tissue protein synthesis is activated in the interstitial cell fibroblasts soon after cadmium exposure.

Aerosols↗
PubMed1981

Familial type II hyperlipoproteinemia with coronary heart disease: effect of diet-colestipol-nicotinic acid treatment.

Heterozygous familial type II hyperlipoproteinemia (F type II) is primarily manifested in hypercholesterolemia (due to low density lipoprotein-cholesterol [LDL-C] elevation) and premature coronary heart disease (CHD). We studied sequentially the effects of low cholesterol-low saturated fat-low simple carbohydrate diet; diet and colestipol, 30 g/day; and diet, colestipol, plus nicotinic acid (NA) 3 to 7 g/day on plasma cholesterol (Ch), LDL-C, triglyceride (TG), high density lipoprotein-cholesterol (HDL-C) and angiographically documented coronary arterial lesions of 32 F type II patients. Effective control of F type II resulted in arresting the progression of angiographically demonstrated coronary arterial lesions.

Adult↗
PubMed1980

Hepatoma presenting as a single cavitary lung mass.

A patient who had had a lobectomy for a large cavitary lung mass died one month later. An autopsy was performed and pathologic review of surgical and postmortem specimens confirmed that the original lung lesion was metastatic hepatoma. Excavating solitary metastases from primary adenocarcinomas represent the rarest form of cavitary metastatic lesion, and this is the first report of hepatocellular carcinoma presenting as a single cavitary lung mass.

Carcinoma, Hepatocellular↗
PubMed1979

Peribronchiolar fibrosis following acute experimental lung damage by cadmium aerosol.

Following exposure to an aerosol of 0.1 per cent. (0.005M) cadmium chloride in physiologic saline, rat lungs were examined at 1 hour, 1, 2, 3, 4, 5, 7, 10 and 21 days. Light microscopy showed that damage was most marked about respiratory bronchioles with a prominent increase in interstitial cells. Up to 3 days the intestitial cells were closely packed and monocytic in type, but on the fourth and fifth days, the cellular density had decreased and elongated cells resembling fibroblasts appeared. By 7 days the interstitial cells were predominantly fibroblastic. Ultrastructurally the fibroblasts were active with prominent rough endoplasmic reticulum and numerous, single, haphazardly scattered collagen fibrils in lacunae at the cell margins. At 21 days after injury, interstitial collagen was seen as well organised, mature bundles. The fibrosis was seen in a peribronchiolar position with distoration of the bronchiole and adjacent alveoli. We suggest that the peribronchiolar localisation of fibrosis is the probable cause of centriacinar emphysema resulting from acute cadmium fume poisoning in man.

Acute Disease↗
PubMed1979

Myointimal plaques in pulmonary vascular sclerosis associated with interstitial lung fibrosis.

In interstitial fibrosis of the lung, pulmonary vessels show priminent sclerotic changes. We have studied arteries in lung biopsies from patients with lung fibrosis of varied etiology using light and electron microscopy. It was found that the sclerotic change is essentially confined to arteries within fibrotic areas, areas of "nonfibrotic" lung having vessels with no intimal thickening. The changes are most striking in arteries with an external diameter of 500 micrometer. or greater (p less than 0.001), although smaller sized vessels also show significant changes. Ultrastructurally, the plaques are composed of typical smooth muscle cells with basement lamina, pinocytotic vesicles, dense bodies, and cytoplasmic microfilaments. These arterial changes could result from damage to the blood vessel which accompanies the mechanism producing lung fibrosis. Alternatively, the myointimal change could conceivably be part of an adaptive response following the establishment of fibrosis. In either instance, the narrowing would decrease blood flow to physiologically disadvantaged areas of the lung, and the muscle fibers might play an active role in reducing the blood flow.

Adult↗
PubMed1978

Bronchial mucus hypersecretion induced by elastase in hamsters: ultrastructural appearances.

Male golden hamsters were exposed to a solution of purified pancreatic elastase by intratracheal injection. They developed panlobular (panacinar) emphysema and, in addition, were found to show severe goblet cell metaplasia in the major bronchi. The metaplastic change in the respiratory epithelium was associated with persistence of a fenestrated sheet of mucus, widely present throughout the bronchial tree, which was greater in amount than that in either unexposed or saline exposed controls. Transmission electron micrography showed a striking increase in size of individual goblet cells, due to increased numbers of secretory droplets which were also much larger and paler than in control bronchi. Ciliated cells appeared smaller than normal due to compression by the swollen goblet cells. The presence of prominent dilatation of the endoplasmic reticulum and the increased frequency of secretory droplet release from the luminal surface stronly suggest that the goblet cell changes were due to increased formation and secretion of mucus into the damaged bronchi. These experiments show that a single exposure to elastase produces both severe panlobular emphysema and goblet cell metaplasia. The changes resemble several of the anatomic features of chronic obstructive lung disease in man for which this injury may be a suitable model.

Animals↗
PubMed1978

Acute lung injury induced by cadmium aerosol. II. Free airway cell response during injury and repair.

This paper presents a study of the effects of cadmium chloride aerosol on free airway cell populations. Rats were given a single exposure to aerosolized 0.005 M CdCl2 dissolved in physiologic saline. CdCl2 exposure induced a fivefold increase to 43.2 X 10(6) total cells at 4 days as compared with 11.1 X 10(6) in saline-exposed controls and 8.4 X 10(6) in unexposed rats (P less than 0.001). Differential counts showed a peak of polymorphonuclear leukocytes (PMN) at 3 days after CdCl2 exposure, whereas values for saline-exposed animals showed no change from values for unexposed animals (P less than 0.001). Four days after CdCl2 exposure thepredominant cell was the alveolar macrophage (AM), which showed a highly significant increase in number and size over saline-exposed and unexposed animals. A significant increase in lymphocytes also occurred, with a peak at 4 days. At 10 days after exposure, AM were still more numerous after CdCl2 exposure (P less than 0.001), but all other cell types had returned to control levels. Correlation with previous ultrastructural studies on CdCl2 exposure suggested the peak of PMN coincided with Type I cell necrosis. In contrast, AM predominated durion and phagocytosis occur.

Aerosols↗
PubMed1977

Irreversible bronchial goblet cell metaplasia in hamsters with elastase-induced panacinar emphysema.

A single intratracheal instillation of pancreatic elastase in hamsters induces a lesion resembling human panacinar emphysema. This paper reports the occurrence of irreversible goblet cell metaplasia in the bronchial epithelium of hamsters similarly exposed to elastase. The goblet cell change was dose related; a dose of 0.1 mg/100 g body wt or less at 16 days, produced slight or moderate goblet cell metaplasia in fewer than half the animals, whereas 84% of animals treated with a dose between 0.2 and 0.5 mg/100 g body wt developed goblet cell metaplastic lesions, more than half of which were considered to be severe. The percentage of goblet cells in the epithelium of elastase-treated hamsters (32.5) was significantly higher (P less than 0.005) than that of unexposed (12.2) and saline-exposed controls (18.7). All hamsters examined 6 and 12 mo after elastase treatment showed the lesion. The pathogenesis of the changes is unclear but the possibility is raised that the bronchial changes may be due to disturbance of an endogenous protease-antiprotease system. The findings suggest the hypothesis that, under appropriate circumstances, a single pulmonary insult in man could lead to a permanent lung injury demonstrating the anatomic lesions of both chronic bronchitis and panacinar emphysema.

Animals↗
PubMed1977

The hamster as a model of chronic bronchitis and emphysema in man.

Male hamster weighing 100-140 g were exposed to 50-500 microgram purified elastrase per 100 g body weight by intratracheal injection. The hamster were killed at intervals up to 12 months after treatment, and their lungs were examined grossly and microscopically. At 8 days after treatment, the lungs appeared to have a greater volume than the controls. At 16 days, the lungs remained inflated when the pleural cavity was opened. Alveolar size was increased in proportion to the dose of elastase. From 16 days onward, the emphysematous lesion was well established. The number of goblet cells in the bronchi also increased. Counts of goblet cells as a proportion of all bronchial lining cells showed that goblet cells more than doubled in number in elastase treated hamsters as compared with controls. The mechanism for the two lesions caused by elastase was not clear. It was concluded that the elastase treated hamster is a useful model for studies of the pathogenesis of chronic bronchitis and emphysema in man.

Animals↗
PubMed1976

The evolution of biochemical damage in the rat lung after acute cadmium exposure.

Rats were exposed once to a polydisperse aerosol of 0.005 M cadmium chloride for 2 hours. Controls were saline-exposed rats and unexposed rats. Total extractable lipid, malate, lactate, isocitrate, and glucose-6-phosphate dehydrogenases were measured on the organelle-free cytosol from homogenized lungs at periods up to 10 days after exposure. The wet weight, dry weight, ribonucleic acid, and deoxyribonucleic acid content of the lungs were also determined. Ultrastructural appearances were studied at the same time intervals in a separate experiment. Total lipid content, lactate dehydrogenase, and glucose-6-phosphate dehydrogenase activities showed approximate doubling by the fourth day after exposure, this change coinciding with doubling of wet lung weight and total lung deoxyribonucleic acid content. Malate dehydrogenase activity showed a high peak 1 hour after exposure before decreasing to follow the pattern of lactate and glucose-6-phosphate dehydrogenase. The changes found may be a nonspecific reaction to lung injury, comparable with oxygen, ozone, and nitrogen dioxide. These results in Type II cell proliferation, which would enhance glucose-6-phosphate dehydrogenase content and resistance to peroxidation. Lipid accumulation could be a similar response. However, the initial elevation in malate dehydrogenase activity is more in keeping with a specific mitochondrial injury (with some ultrastructural support), perhaps with leakage of mitochondrial enzymes. This suggests that there may be more than one mechanism at work in the injury. It is significant that despite the marked structural and functional changes, none of the rats died after the exposure, which makes the injury a model worthy of further investigation.

Aerosols↗