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Biomedical subjects

P Kimbel

Publications and source records attributed to P Kimbel.

36 records · Page 2Linked to original sources

Purification and characterization of canine alpha-1-antiproteinase.

The principal canine plasma protease inhibitor, alpha-1-antiproteinase, has been purified 90-fold with a 25% yield to apparent homogeneity. The purification scheme includes anion-exchange chromatography, to separate away the bulk of the serum albumin; affinity chromatography by insolubilized concanavalin A, to remove most of the other serum proteins as well as traces of albumin; and, finally, sizing on Sephacryl-S-200. Unique to this purification scheme is the batch use of insolubilized hemoglobin--Sepharose beads to remove the ubiquitous contaminant haptoglobin. The purified material has an apparent molecular weight of 58 000, 11.2% carbohydrate, and an E280nm1% = 5.82, and can be separated by isoelectric focusing into at least two distinct forms with pI values of 4.40 and 4.52. In addition, canine alpha-1-antiproteinase is immunologically distinct from human alpha-1-antiproteinase.

Amino Acids↗

Pulmonary vascular changes following air embolism in the dog.

The effect of an intravenous injection of air in a dose of 1 ml/kg body weight was determined in 15 healthy mongrel dogs. In 4 control dogs the mean pulmonary artery pressure rose to 2-3 times the resting values at 30 seconds, and carbon monoxide diffusing capacity and pulmonary capillary blood volume decreased by half. In the animals pretreated either with heparin or with methysergide (antiserotonin group) the results were the same as in the control animals. In the vagotomized dogs, the rise in pulmonary artery pressure was not significant, and the decrease in pulmonary capillary blood volume was of lesser magnitude and shorter duration than in the control and the antiserotonin dogs. It is concluded that the intravenous injection of air in supine dogs causes a transient obstruction of small pulmonary arteries. Evidence is presented to implicate a vagal mechanism in both main aspects of the response, namely the pulmonary artery pressure rise, and the partial obstruction of the pulmonary capillary bed. These studies offer additional explanation of the symptoms of respiratory distress observed in rapid decompression.

Animals↗

Experimental emphysema induced with purified human neutrophil elastase: tissue localization of the instilled protease.

Human neutrophilic polymorphonuclear leukocyte (PMN) elastase was purified by affinity chromatography to greater than 95% homogeneity as judged by disc-gel electrophoresis. Dog lung elastin was prepared from alveolar-enriched tissue by prior extraction of soluble and collagenous lung proteins with 0.1 M NaOH at 98 degrees C. Digestion of the remaining insoluble residue by the purified PMN enzyme was monitored by Lowry assay of acid-soluble peptides released. The PMN enzyme possessed 60% of the digestive activity of crystallized porcine pancreatic elastase (weight:weight comparison) when tested in vitro against this substrate in phosphate-NaCl buffer at pH 7.5. Whole tissue studies were then performed in lungs of laboratory animals. One-ml samples containing purified PMN elastase were instilled into lavaged and saline-perfused isolated dog lung at the level of the sixth to seventh generation bronchus. Treatment with 384 mug of the PMN enzyme produced anatomic emphysema after a 90-min incubation at room temperature, which was comparable to that produced by 100 mug of porcine pancreatic elastase. Frozen sections of treated and control lungs were examined for the presence of PMN elastase by the indirect immunoperoxidase method using a monospecific rabbit antiserum against PMN elastase as the primary stain. Light microscopy revealed elastase bound to connective tissue in the treated lungs, in close proximity to aldehyde-fuchsin-counterstained elastic fibers. A similar experiment was tn of enzyme solutions containing 1;0 mg of elastase per ml produced discrete lesions within 90 min, as before. Light microscopic studies in conjunction with the indirect immunoperoxidase staining method again demonstrated elastase in association with connective tissue elements in the lesion area. In addition, part of the instilled protease could be demonstrated within alveolar macrophages. Electron microscopy combined with immunoperoxidase staining revealed direct attachment of th einstilled enzyme to elastic fibers within alveolar septa. In enzyme-treated tissue, some septa showed severe depletion of intercellular structures with the exception of colalgen, which was generally preserved. These results show that human leukocyte elastase penetrated dog alveolar septal connective tissue after airway instillation and that the enzyme attaches to elastic fibers, inducing histologic changes comparable to thos seen in human emphysema.

Animals↗

Chronic obstructive airway diseases. Current concepts in diagnosis and comprehensive care.

Physicians and paramedical personnel often find the early diagnosis and differentiation of obstructive airway diseases to be a challenging problem. The history and physical examination are often not enough to allow the physician to detect either the presence of, or determine the type of, disease present. Patterns of pulmonary function abnormality to determine the presence of obstructive or restrictive defects are discussed. Guidelines useful in the differentiation of obstructive airway diseases are presented. Once a patient with COAD is assessed, the physician needs to outline a therapeutic program after establishing goals with the patient. These goals include (1) improved ability for the patient to achieve relief from symptoms and (2) improved capacity to carry out the activities of daily living. The therapeutic modalities available for the comprehensive care of patients with COAD are discussed. These include general factors such as patient and family education, avoidance of smoking and other inhaled irritants, avoidance of infection, a minimum stress environment, high fluid intake, and proper nutrition. The appropriate use of the medications most commonly employed in the teatment of these patients, eg, bronchodilators, expectorants, antimicrobials, corticosteroids, cromolyn, digitalis, and diuretics, are individually discussed. The use of such respiratory therapy techniques as aerosol therapy, intermittent positive pressure breathing, and oxygen therapy are considered. Application of the specialty of rehabilitation medicine to patients with obstructive airway disease is described. This includes physical therapy with breathing retraining, clapping and postural drainage, and exercise reconditioning, occupational therapy with attention to energy conservation in activities of daily living, psychological considerations, and vocational rehabilitation. Definite benefits that can be demonstrated if the physician employs this type of systematic respiratory care program include a decrease in the frequency and duration of hospital admissions, socioeconomic gains from reduced hospitalizations, a reduction in anxiety, depression and somatic concern, the return of patients to positions of employment and the establishment of a better quality of life. Persistence in making sure the patient continues in a systematic program, including both pharmacological and nonpharmacological modalities, may be the means of assuring maintenance or even improvement in his health. The day-to-day treatment for the majority of patients should remain in the hands of the primary physician. However, community resources must be established to allow the primary physician to provide these patients with adequate comprehensive respiratory care. Development of three levels of care (the primary physician, community respiratory rehabilitation units, and the regional respiratory center) should make superior respiratory care available to every patient with obstructive airway disease.

Adrenal Cortex Hormones↗