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Biomedical subjects

J O Harris

Publications and source records attributed to J O Harris.

At least 37 records · Page 2Linked to original sources

Prospective evaluation for pneumonectomy using perfusion scanning: follow-up beyond one year.

Thirty-eight high-risk patients (forced expiratory volume in one second [FEV1] less than 2.0L or maximum voluntary ventilation [MVV] less than 50 per cent of predicted) were observed for a minimum of one year after pneumonectomy for carcinoma of the lung. Operability was assessed by calculating a predicted postoperative FEV1 (based on the right-left fractional perfusion estimated by a perfusion lung scan) and requiring this predicted postoperative value to exceed 800 ml. No other invasive physiologic studies were performed before surgery. At one year, 23 of 38 patients were still alive, and 13 of 38 patients survived to the end of the second year. At five years, two of 15 patients were alive with no evidence of metastatic disease. This simple physiologic approach involves widely available techniques and, in patients with lung cancer who have compromised pulmonary function, appears to result in acceptable survival over a longer period.

Carcinoma↗

5-Hydroxytryptamine uptake by lungs of hamsters with pulmonary emphysema.

Elastase-induced emphysema in hamsters was used as a model to determine whether this type of chronic lung injury affected the metabolic function of pulmonary endothelium. 5-Hydroxytryptamine (5-HT) uptake was studied in isolated perfused lungs of hamsters from a control group and from those with emphysema of various severity. After measuring 5-HT uptake, we determined the mean linear intercept and internal surface area for each lung. The concentration of 5-HT used in the perfusate ranged from the level in the resting hamster to supraphysiologic levels. The results reveal that elastase-induced emphysema does not affect 5-HT uptake by the isolated perfused hamster lung despite significant loss of alveolar surface area.

Animals↗

Desquamative interstitial pneumonitis. Characterization of free intraalveolar cells.

There is some disagreement concerning the nature of the free intraalveolar cells in desquamative interstitial pneumonitis, although the greatest weight of evidence suggests them to be alveolar macrophages. We have obtained these cells by bronchoalveolar lavage from two patients with desquamative interstitial pneumonitis and studied their in vitro antibacterial activity and their ultrastructural morphology. Our results indicate that the free intraalveolar cells in these two patients were alveolar macrophages with normal antibacterial function.

Humans↗

Creutzfeldt-Jakob disease: patterns of worldwide occurrence and the significance of familial and sporadic clustering.

The worldwide epidemiology of Creutzfeldt-Jakob disease (CJD) is presented from an analysis of 1,435 patients. In the United States, the average annual mortality rate is at least 0.26 deaths per million. Temporal-spatial clustering of cases was not found in the United States, but reports from other countries indicate that such clustering does occur. Fifteen percent of the cases were of the familial type, suggesting a genetic susceptibility to infection. Iatrogenic transmission by corneal transplantation and neurosurgical operations has occurred, and the possibility is raised that previous surgery or preexisting neurological operations has occurred, and the possibility is raised that previous surgery or preexisting neurological disease may be associated with an increased risk of developing CJD. It remains to be determined whether the virus of CJD is maintained only by patient-to-patient transmission, has a zoonotic reservoir such as scrapie, or causes widespread latent infection of man that is occasionally activated.

Adolescent↗

Pulmonary alveolar proteinosis: abnormal in vitro function of alveolar macrophages.

Pulmonary alveolar proteinosis is characterized by the accumulation of granular proteinaceous material within the alveoli of the lung. It is well established that patients with pulmonary alveolar proteinosis have a high incidence of complicating pulmonary infections, which suggests that the function of the alveolar macrophages is abnormal. To investigate the function of these cells, they were obtained from two patients by pulmonary lavage with physiologic saline solution and were incubated with Staphylococcus aureus in vitro. The decline in viable organisms from the culture was measured and compared with results obtained with normal alveolar macrophages. On the basis of decreased phagocytosis, results indicate that pulmonary alveolar macrophages from these patients had defective antibacterial function.

Bacterial Infections↗

Human alveolar macrophage proteolytic enzyme activities in chronic obstructive pulmonary disease. Lack of correlation with functional abnormalities.

The occurrence of emphysema in people deficient in alpha1-antitrypsin and the production of emphysema in experimental animals with elastolytic enzymes suggest proteolysis as a mechanism for the development of emphysema. To investigate the possible role of pulmonary alveolar macrophages in the pathogenesis of emphysema, we measured elastase, acid protease, and elastase-like esterase activities in macrophages from patients with chronic obstructive lung disease and attempted to correlate the level of enzyme activity with the severity of pulmonary function abnormality measured in these patients. Compared to values for cigarette smokers with normal pulmonary function, these macrophage enzyme activities were not increased in patients with chronic obstructive lung disease, and there was no correlation of high elastase activity with more severe degrees of pulmonary function abnormality. These findings lead us to believe that the absolute level of proteolytic enzymes in pulmonary alveolar macrophages is not in itself a determinant of emphysema.

Adult↗

Prospective evaluation for pneumonectomy using the 99mtechnetium quantitative perfusion lung scan.

We evaluated 33 high-risk patients before pneumonectomy, all of whom had a forced expiratory volume in one second (FEV1) of less than 2.0 L before surgery. A quantitative perfusion lung scan was used to assess the right-left distribution of blood flow. A predicted postoperative FEV1 was calculated from the information on the lung scan and the preoperative FEV1. If this calculated value exceeded 800 ml, the patient was physiologically cleared for surgery up to and including a pneumonectomy. Surgery was otherwise believed to be contraindicated in the absence of studies using balloon occlusion. Perioperative mortality (less than or equal to 30 days after surgery) was found to be 15 percent (5/33). In surgery of this magnitude, we find this to be an acceptable percentage of mortality and have continued to use these simple physiologic criteria to determine whether a patient can tolerate pneumonectomy.

Aged↗

The extracellular metalloprotease of Serratia marcescens. 2. Comparison with trypsin and substrate specificity.

The proteolytic activity of the extracellular protease of Serratia marcescens was compared with that of trypsin on N, N-dimethyl casein. The peptides produced from exhaustive hydrolysis of alpha casein by the protease and by trypsin were of similar size as measured by gel filtration on P-10 Agarose. We conclude that the protease of S. marcescens in an endopeptidase with trypsin-like activity on proteins, producing oligopeptides. End group analysis of the peptides formed by the S. marcescens protease suggests that the protease has a unique substrate specificity, hydrolyzing only a peptide bond whose carboxyl group is donated by proline. The protease was inactive on the synthetic peptides with proline donating the carboxyl group, but hydrolyzed various types of natural proteins. Its narrow and novel substrate specificity makes this enzyme a potential tool for the determination of the primary structure of proteins.

Endopeptidases↗

The extracellular metalloprotease of Serratia marcescens: I. Purification and characterization.

An extracellular protease of Serratia marcescens produced during growth on skim milk medium was isolated by ethanol precipitation. The protease was purified by salt fractionation, DEAE-cellulose ion exchange chromatography and gel filtration chromatography on Agarose P-100. It has a broad optimum from pH 6.0 to 9.0 and a temperature optimum of 45 degrees C for proteolytic activity on casein. It was classified as a metallo-protease by virtue of its inactivation by metal-ion chelators and reactivation by ferrous ions. Proteolytic activity was not affected by diiso-propylfluorophosphate, p-chloromercuribenzoate and dithiothreitol.

Binding Sites↗

Cellular and humoral bronchopulmonary immune response of rabbits immunized with thermophilic actinomyces antigen.

The immunologic events involved in the pathogenesis of human hypersensitivity pneumonitis are poorly understood. To delineate better the cellular and humoral bronchopulmonary response to host challenge with an important agent for hypersensitivity pneumonitis, an animal model was developed. Rabbits intratracheally inoculated with Micropolyspora faeni antigen developed histologic lesions resembling hypersensitivity pneumonitis in man, characterized by a mononuclear cell interstitial reaction and a marked increase in the number of intra-alveolar cells. This reaction was intense 8 days after immunization and progressively decreased in intensity, with complete resolution occurring, in some instances, by 3 weeks. The increased intra-alveolar cells were predominantly macrophages, but soon after immunization, greater numbers of lymphocytes and granulocytes were present. Associated with the intra-alveolar macrophage response was the appearance of "activated" macrophages, based on increased glucose oxidation and ultrastructural appearance. The immunized rabbits demonstrated Arthus-type skin reactions, as well as delayed hypersensitivity skin reactions after intradermal injection of M. faeni antigen. Alveolar macrophage migration was significantly inhibited in immunized rabbits in the presence of M. faeni antigen, suggesting that specifically sensitized lymphocytes were present in the free bronchoalveolar cell population. Intratracheal inoculation with M. faeni resulted in the production of anti-M. faeni-precipitating antibodies in the sera of all animals and in bronchoalveolar secretions in 15 of 16 inoculated rabbits. The concentrations of IgG and IgA in lung-wash fluid were significantly greater in immunized animals. In the immunized rabbits, the mononuclear cell response, positive M. faeni-induced direct migration inhibition factor assays, and delayed skin reactivity strongly suggested the presence of a delayed hypersensitivity component in disease pathogenesis. The presence of precipitating antibody and the increased concentrations of immunoglobulins were consistent with stimulation of the humoral immune system; however, the role of humoral mechanisms in the pathogenesis of the pulmonary lesions is less certain than that of delayed hypersensitivity.

Animals↗

Comparison of proteolytic enzyme activity in pulmonary alveolar macrophages and blood leukocytes in smokers and nonsmokers.

Proteolysis (or more specifically, elastolysis) of the lung may be involved in the pathogenesis of pulmonary emphysema. To investigate the human alveolar macrophage as a potential mediator of lung damage, elastase-like esterase and protease activity was determined in these cells as well as in alveolar lavage fluid and in peripheral blood leukocytes. Bronchoalveolar lavage was used to obtain alveolar cells and fluid in normal volunteers who were divided into two groups according to cigarette smoking history, nonsmokers and smokers. Results of these studies revealed that human alveolar macrophages possess a high activity of both elastase-like esterase and protease. Furthermore, the alveolar macrophages of cigarette smokers has a significantly greater elastase-like esterase and protease activity than those of nonsmokers. When the 4- to 5-fold increase in the number of macrophages found cigaretts smokers is taken into account there was approximately 10 times more elastase-like esterase activity and 18 times more protease activity within macrophages in the alveolar spaces of cigarette smokers' lungs. This makes the alveolar macrophage a poten potential source of proteolytic enzymes in man.

Adult↗

Alpha-1-antitrypsin content in the serum, alveolar macrophages, and alveolar lavage fluid of smoking and nonsmoking normal subjects.

The content of alpha-1-antitrypsin in the serum, alveolar lavage fluid, and alveolar macrophages of smokers and nonsmokers was studied. Bronchoalveolar lavage was used to obtain alveolar fluid and macrophages from normal volunteers, and alpha-1-antitrypsin and albumin were measured using the electroimmunodiffusion technique. The serum level of inhibitor was not different between the two groups, while the total lavage fliud content of alpha-1-antitrypsin was increased in the smokers. The level of alpha-1-antitrypsin was also significantly greater (P less than 0.001) in the alveolar macrophages of the smokers suggesting the possibility of chronically increased alveolar levels in the cigarette smoker as a possible protective mechanism against proteolysis.

Albumins↗