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Biomedical subjects

J G Clark

Publications and source records attributed to J G Clark.

At least 73 records · Page 4Linked to original sources

Modulation of collagen production following bleomycin-induced pulmonary fibrosis in hamsters. Presence of a factor in lung that increases fibroblast prostaglandin E2 and cAMP and suppresses fibroblast proliferation and collagen production.

To elucidate mechanisms involved in the regulation of lung collagen content we studied hamsters with bleomycin-induced pulmonary fibrosis. Lung collagen in this model is increased as the result of greatly increased lung collagen synthesis rates. However, collagen synthesis rates are subsequently restored to normal. Hamster lung explants from both normal and bleomycin-exposed hamsters were cultured, and the effects of explant conditioned medium (CM) on lung fibroblast (IMR-90) proliferation and collagen production in vitro were determined. Lung explant CM increased fibroblast prostaglandin (PG)E2 production and intracellular cAMP, and decreased both fibroblast proliferation and collagen production in a dose-dependent manner. Greater activity was observed with lung explant CM from bleomycin-exposed lungs. Incubation of fibroblasts with indomethacin prior to addition of CM blocked CM-mediated changes in PGE2 and cAMP and inhibited changes in fibroblast proliferation and collagen production. Exogenous PGE2 or dibutyryl cAMP also suppressed fibroblast proliferation and collagen production. The suppressive activity in lung-conditioned medium is nondialyzable, has an apparent molecular weight of 15,000-20,000 by gel filtration, and is heat-stable. It is not species-restricted since CM from hamster lung affected human and hamster lung fibroblasts similarly. Activity is present preformed in lung and bronchoalveolar lavage fluid, although bronchoalveolar macrophages produce a nondialyzable factor in culture which suppresses fibroblast proliferation. The suppressive activity identified in fibrotic lung may represent a means for limiting collagen accumulation following tumor injury.

Animals↗

Assessment of three modes of alaryngeal speech with a synthetic sentence identification (SSI) task in varying message-to-competition ratios.

The intelligibility measures and listener preference rankings of pulmonary esophageal speech following tracheo-esophageal puncture (TEP) surgery were assessed relative to traditional esophageal speech, artificial laryngeal speech, and normal laryngeal speech. Intelligibility rankings were obtained with sentence length stimuli i the presence of a background competing message at varying message-to-competition ratios. Results for 20 normal-hearing adult subjects showed that although pulmonary esophageal speech was the most preferred of the alaryngeal speech modes, it was the least intelligible in the two most difficult listening conditions (-5-dB and -10-dB message-to-competition ratios).

Adult↗

Bleomycin-induced pulmonary fibrosis in hamsters: effect of neutrophil depletion on lung collagen synthesis.

The development of pulmonary fibrosis in hamsters after the intratracheal instillation of bleomycin is attended by exudation of polymorphonuclear leukocytes (PMNs), but the function of these cells is unknown. In this study, we examined the effect of PMN depletion on lung collagen synthetic rate in bleomycin-treated hamsters. Antiserum to hamster PMNs was produced in rabbits and injected intraperitoneally into hamsters on the fourth through seventh days after intratracheal instillation of bleomycin or saline. Control animals received either normal rabbit serum (NRS) or no serum. Anti-PMN serum (APS) significantly reduced PMN exudation after bleomycin treatment through the eighth day (p less than 0.01). Collagen synthetic rate measured in lung explant cultures was increased in all bleomycin-treated groups compared with that in the saline injected control group (p less than 0.005). Collagen synthesis was greater in neutrophil-depleted bleomycin-treated hamsters than in bleomycin-treated animals receiving NRS or no serum on Days 8 (p less than 0.01) and 12 (p less than 0.05). In APS-treated hamsters, the proportion of protein synthesis directed toward collagen synthesis was increased above other bleomycin-treated groups, suggesting that collagen synthesis is selectively increased in neutrophil-depleted hamsters with bleomycin-induced pulmonary fibrosis.

Animals↗

Bleomycin-induced synthesis of type I procollagen by human lung and skin fibroblasts in culture.

Bleomycin is a chemotherapeutic agent sometimes associated with pulmonary fibrosis and skin lesions in patients undergoing treatment. We examined the mechanisms of increased collagen deposition on bleomycin-induced fibrosis by incubating human lung and skin fibroblast cultures with [14C]proline; the synthesis of [14C]hydroxyproline relative to DNA or cell protein was taken as an index of procollagen formation. Procollagen synthesis by lung cells in the presence of 0.1 and 1.0 microgram/ml bleomycin was significantly increased and similar results were obtained with skin fibroblasts. The relative synthesis of genetically distinct types of collagen was measured by isolating the newly synthesized type I and type III procollagens by DEAE-cellulose chromatography. The proportion of type III procollagen of total newly synthesized procollagen in control lung fibroblast cultures was 17.4 +/0 0.6% (mean +/- S.E.) while the corresponding value in cells incubated in 1 microgram/ml bleomycin was 12.5 +/- 0.6% (n = 6, P < 0.01). Similar results were obtained when the ratios of newly synthesized type I and type III collagens were estimated by interrupted polyacrylamide disc gel electrophoresis in sodium dodecyl sulfate after a limited proteolytic digestion with pepsin. The results indicate that the increased procollagen synthesis induced by bleomycin in fibroblast cultures is predominantly directed towards the synthesis of type I procollagen.

Bleomycin↗

Sequential changes in plasma lipoproteins and body fat composition during polyunsaturated fat feeding in man.

1. The early effects of a moderate polyunsaturated fat diet on the composition of circulating lipoproteins and adipose tissue fatty acids were measured in five healthy adults. 2. The fatty acid content and gross composition of the three major plasma lipoprotein fractions altered within 7 d of treatment. The response of depot fat was slower but did show a significant and progressive change after 14 d on the diet. 3. The efficiency of the moderate diet in changing the composition of the lipoproteins suggests that it should be equally effective in altering their metabolic handling.

Adipose Tissue↗

Lung collagen in type IV Ehlers-Danlos syndrome: ultrastructural and biochemical studies.

A patient with type IV Ehlers-Danlos syndrome developed recurrent pneumothoraces. At operation for poudrage of the pleura, an apical bulla was resected. Biochemical analysis of the lung tissue revealed increased solubilization of collagen by acetic acid extraction and by pepsin proteolysis. The relative proportion of type III collagen in the pepsin-solubilized collagen fraction was markedly decreased. Fibroblasts cultured from the patient's lung produced less type III procollagen relative to type I procollagen than control lung fibroblasts. Electron microscopic examination of the lung tissue showed dilated endoplasmic reticulum of the fibroblasts, and collagen fibers were normal. These observations suggested that the structural abnormalities in the lung that led to pneumothorax in this patient were due to deficiency of type III collagen.

Adult↗

Pulmonary cavitation and massive hemoptysis caused by an unsuspected intraparenchymal foreign body.

A patient presented with massive hemoptysis, and a chest roentgenogram revealed a right lower lobe cavity which contained a movable mass of soft tissue density. He had sustained a gunshot wound to the chest seven years earlier. Thoracotomy was performed for uncontrollable hemoptysis, and parenchymal cavitation was found which contained a plastic foreign body. We retrieved a film following the original injury which revealed a mass density that proved to be a plastic wadding capsule from a shotgun shell. This type of complication from intraparenchymal foreign bodies is discussed and the unusual roentgenographic presentation of this patient is considered.

Adult↗

Collagen biosynthesis in bleomycin-induced pulmonary fibrosis in hamsters.

Bleomycin results in pulmonary interstitial fibrosis characterized by accumulation of collagen. We studied the mechanisms of this accumulation in hamsters 4 to 24 days after intratracheal injection of 1 U of bleomycin. Lung collagen was significantly increased within 11 days. Collagen synthesis was increased 10-fold in explant cultures obtained 8 days after injection. Prolyl hydroxylase activity and the degradation of newly synthesized collagen were also increased proportionally to collagen synthesis. Total protein synthesis also increased but not as much as collagen synthesis. We conclude that the accumulation of collagen in the lung following proceeds from an increased rate of collagen synthesis that is maximal early after injection and persists for at least 24 days after exposure.

Animals↗

Cults.

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Attitude to Health↗

Metabolic and cellular profile testing in calves under feedlot conditions: minerals, electrolytes, and biochemical components--reference values.

Blood serum samples were obtained from 114 crossbred calves on a feed trial under feedlot conditions at the end of a 56-day feeding period. Average values for 19 blood components were determined. The effects of the 3 trial rations and 2 electrolyte treatments were analyzed. Except for inorganic phosphates, urea nitrogen, cholesterol, glucose, alanine aminotransferase, and alkaline phosphatase most mean values were similar to those in dairy cattle. Urea nitrogen values differed significantly (P less than 0.05) in animals fed different rations apparently reflecting the crude protein content of each ration. The mean values presented can be used as base-line data for comparison with other similar studies or with values from diseased animals.

Animal Feed↗

Metabolic and cellular profile testing in calves under feedlot conditions: minerals, electrolytes and biochemical components--changes over time in feedlot.

The concentration of 19 mineral, electrolyte, and biochemical components in blood serum of 114 calves under feedlot conditions were measured or calculated over a 58-day period (2 days before and 56 days during a feed trail). The purpose was to evaluate the variability in the concentration of these components over time. The blood was collected on 7 sampling dates and analyzed on the day following sampling. Generally, the serum concentrations of the components that were measured varied considerably over the first 3 weeks of the feeding period and then had a tendency to level off during the 2nd part of that period.

Alanine Transaminase↗

Metabolic and cellular profile testing in calves uncer feedlot conditions: blood cellular components--reference values and changes over time in feedlot.

The cellular components of the blood of 114 calves were measured under feedlot conditions. The results suggest that certain cellular components of the blood of a group of crossbred feedlot-type calves which are homogeneous only with regard to weight are reasonably uniform. More specifically, all red blood cell components have coefficients of variation of less than 10%. The white blood cell counts underwent drastic changes over the first 2 sampling dates, ie, before and after transport and processing of the calves. Later, in the feeding period, the cell counts readjusted to more stable levels. The results were compared with such values obtained from dairy cattle. The total erythrocyte count, total leukocyte count, and red blood cell components were found to be slightly higher in these feedlot calves than in dairy cattle. The difference might partly be due to age. The mean values reported can be used as a base for comparison with values obtained from other such studies or from studies of disease processes in cattle under feedlot conditions (or both).

Animal Feed↗