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Biomedical subjects

K H Kilburn

Publications and source records attributed to K H Kilburn.

At least 73 records · Page 4Linked to original sources
PubMed1982

Neonatal deaths and pulmonary dysplasia due to D-penicillamine in the rat.

D-penicillamine, added to a low copper diet fed through pregnancy or given by gavage to pregnant rts which were on a copper-deficient or a normal diet produced fetal resorptions and malformations. Doses of 300 to 400 mg per day for 6 days (days 9-14 or gestation) with a diet normal for copper prevented maternal weight gain and at 350 or 400 mg/day caused fetal death on day 16 or 17. Forty percent of offspring had tracheobronchomegaly and 42% had cystic lungs. Associated abnormalities included pleural hemorrhages, dilated esophagi, and anaerated lungs. The lungs had large, poorly formed, thick-walled acini without partitioning and a thick rim of connective tissue around vessels and bronchi. At the higher doses, all members of one of 12 litters had angulation of the spine and half the members of another litter had cleft palates. A postulated mechanism for these alterations in pulmonary connective tissue productive of malformations which model human tracheobronchomegaly and cystic lungs, is interference with lysyl oxidase, a copper-requiring enzyme, which cross-links elastin.

Abnormalities, Drug-Induced↗
PubMed1982

Perinatal death and respiratory apparatus dysgenesis due to a bis (dichloroacetyl) diamine.

N, N1-bis (dichloroacetyl) diamine 1, 8-octomethylenediamine (WIN 18,446) is an experimental drug which was first investigated as a male contraceptive. It is soluble in lipid solvents but not in water. The administration of 1,200 to 1,600 mg/kg to pregnant rats on the tenth day of gestation produced multiorgan fetal malformations. Smaller doses, 400 to 800 mg/kg, especially if divided over 2 or 3 days, caused perinatal death. Thus, 60 to 100% of offspring of rats given WIN 18,446 on the tenth and 11th days of gestation died at birth or within 4 days (Taleporos et al., 78). The present study investigated such deaths. At doses of 200 mg/kg on day 10 or 50 mg/kg on days 10 and 11, 67% of offspring had defective or absent diaphragms, 48% had tracheobronchiomegaly with cystic lungs, and 67% had pleural hemorrhage. At doses of 100 mg/kg given on 1 day or 25 mg/kg each day for 2 days, 50% had tracheobronchiomegaly with cystic lungs and rudimentary acini. At lower doses (18.8 mg/kg X 2 or 12.4 mg/kg X 3), a majority of fetal lungs had rudimentary acini, thick septa, few capillaries, and wide cuffs of perivascular connective tissue. Thus, a chemical given during organogenesis produced dysgenesis of the respiratory apparatus. Varying the dose produced malformed lungs with persistently deficient acini which model such human lung faults as tracheobronchiomegaly (Mournier-Kuhn Syndrome; Mounier-Kuhn, '32), bronchiolar dysplasia (Wilson-Mikity Syndrome), and perinatal death with acinar failure resembling neonatal hyaline membrane disease.

Abnormalities, Drug-Induced↗
PubMed1981

Proteolytic enzymes in bronchopulmonary lavage fluids: cathepsin B-like activity and prolyl endopeptidase.

Two proteolytic enzymes, a cathepsin B-like activity and prolyl endopeptidase activity, were demonstrated in cellular elements and fluids obtained from human bronchopulmonary washings and in fragments of human lung tissue. Model synthetic substrates were used for the determination of enzyme activities. Cathepsin B-like activity was determined with N-benzyloxycarbonyl-L-leucyl-L-leucyl-L-arginyl-2-naphthylamide. The rate of reaction with this substrate was 300 times greater than the rate with alpha-N-benzoyl-DL-arginyl-2-naphthylamide, a substrate commonly used for the determination of cathepsin B activity. Prolyl endopeptidase was determined with N-benzyloxycarbonyl-glycyl-L-prolyl-sulfamethoxazole as the substrate. The two model substrates make possible the determination of enzyme activities in as little as 10 to 50 microliters of lavage fluid. High cathepsin B-like activity and prolyl endopeptidase were generally associated with high macrophage counts in lavage fluids. This observation and the findings that cathepsin B activity is more than 4.5 times higher in normal monocytes than in neutrophils and that prolyl endopeptidase activity could not be detected in normal neutrophils suggest that the enzymes in lavage fluids are mainly derived from macrophages. Large differences in cathepsin B-like activity in certain lavage fluids containing similar macrophage counts suggest the possibility of enzyme induction in these cells. High cathepsin B-like activity and prolyl endopeptidase were also found in lavage fluids after removal of cells by centrifugation. The possibility that these enzymes affect collagen turnover and lung remodeling needs to be explored.

Adult↗
PubMed1978

Silicosis in kaolin workers and firebrick makers.

Nine patients with disabling pneumoconiosis were selected over a three-year period for study because of a work history of kaolin exposure. All had worked in the Missouri firebrick industry. Chest roentgenograms from all nine and lung tissue from two were consistent with silicosis. Worksite analysis of airborne dust at several Missouri firebrick factories revealed that some current workers are exposed to both free silica (up to 4.5%) and cristobalite (up to 8.9%) at levels exceeding the threshold limit value (TLV). Analysis of airborne dust from several kaolin processing plants in South Carolina and Georgia revealed that a few workers are exposed to about 1% free silica at levels occasionally exceeding the TVL. We conclude that silicosis is a serious risk for Missouri kaolin workers and a potential risk for workers in South Carolina and Georgia. A prevalence survey is needed in Missouri to assess the problem.

Aged↗
PubMed1978

The lung of the copper-deficient rat. A model for developmental pulmonary emphysema.

Based on the hypothesis that cross-linked elastin is critical for normal lung structure, lung tissue from copper-deficient rats was studied. Copper deficiency was induced in the second generation by feeding dams a milk-based diet low in copper (less than 1 ppm) during gestation and lactation. The weanlings were fed the same diet until they showed severe signs of deficiency between 6 and 10 weeks of age. Controls animals received the basal diet supplemented with 10 ppm copper. Liver cytochrome oxidase activity, which served as the chief index of deficiency, decreased from a normal level of approximately 80 to 15 mumole/min/g. The lungs of the deficient animals contained 17% less elastin and had 35% larger alveolar spaces (34.7 vs 47.7 intercepts), as determined by the mean alveolar intercept method. The ultrastructure of elastin in the bronchi, arterioles, and alveolar ducts had a "washed out" appearance. To determine the reversibility of the pathology, deficient animals, 5 to 10 weeks of age, were repleted by feeding a copper-supplemented diet for 1, 2, and 3 months. During this period growth resumed, anemia disappeared, and liver cytochrome oxidase returned to normal. There was no improvement in lung structure with regard to alveolar size (28.4 intercepts compared with 43.6 in controls and 35.1 in deficient littermates killed at the start of repletion). The ultrastructure and electron density of pulmonary elastin was restored to near normal. The lung of the copper-deficient rat is proposed as a model for developmental pulmonary emphysema.

Animals↗
PubMed1978

Leukocyte recruitment to airways by aldehyde-carbon combinations that mimic cigarette smoke.

Exposure of Syrian golden hamsters to formaldehyde (3 to 250 p.p.m.) evaporated onto carbon (21 to 805 mg. per cu. m.) recruited polymorphonuclear (PMN) leukocytes to the epithelium of tracheas and intrapulmonary airways which peaked at 24 to 48 hours. Acrolein (less than 6 p.p.m.) on carbon (593 mg. per cu. m.) caused PMN recruitment which was maximal at 12 hours. The vapor phase of cigarette smoke produced PMN leukocyte recruitment of the same magnitude and with the same time course. In contrast, exposure to formaldehyde at doses of 2 to 250 p.p.m. and acrolein at 6 p.p.m. was cytotoxic to airway cells and caused prompt and delayed exfoliation but no recruitment of PMN leukocytes. There was no difference in cytotoxicity when carbon was present. Leukocyte recruitment occurred only when carbon was present, either given simultaneously wiht aldehydes or with adsorbed aldehydes. Thus, aldehyde vapor simulates the cytotoxic effects of particle-free cigarette smoke vapor. Of greater significance is the finding that an aldehyde, formaldehyde or acrolein, inhaled adsorbed on carbon or simultaneously with carbon to hamster airways is chemotactic for PMN leukocytes just as is the vapor phase of cigarette smoke when given simultaneously with carbon particles.

Acrolein↗
PubMed1977

Granulocyte recruitment to airways exposed to endotoxin aerosols.

Guinea pigs were exposed to aerosols of 0.1 mg of Salmonella typhosa endotoxin per ml for 2 or 4 hours, and white cells in blood and in bronchopulmonary lavage were counted at 2, 4, and 6 hours. The lungs of a second group of guinea pigs and hamsters exposed in the same manner were fixed in inflation with osmium tetroxide in fluorocarbon, which retains cells on luminal surfaces of airways. The polymorphonuclear leukocyte counts in cardiac blood were significantly increased, and lymphocyte counts were decreased at 6 hours (P less than 0.05). The number of cells obtained by bronchopulmonary lavage, which were mostly polymorphonuclear leukocytes, increased at 4 hours to 28 million, and at 6 hours, was 26.5 million (P less than 0.01), compared to 5 million cells at the same times in air and in water aerosol control preparations. The polymorphonuclear cell counts on airway cross sections, i.e., (polymorphonuclear cells/epithelial cells) x 100, showed a mean +/- SD peak of 53.9 +/- 10.9 after 4 hours in guinea pigs and a peak of 99.7 +/- 11.0 after 6 hours in hamsters. Alveoli showed no cell recruitment. Platelets were aggregated on surfaces of arterioles facing bronchioles, although counts in blood were unchanged. Neither leukocytes nor airway cells showed damage to their ultrastructure. The time course for airway recruitment and leukocytosis matches that for symptoms after exposure of workers to dusts from natural fodder or fibers. This suggests that leukocyte recruitment to airways by inhaled endotoxin may be part of the mechanism for the fever and chest tightness in occupational disorders.

Aerosols↗
PubMed1977

Normal newborn and adult human lung collagen--analysis of types.

Previous work has shown in experimental animals that lung contains extractable collagen of types I and II and possibly III and IV. The current studies describe the types of collagen which are found in normal newborn and adult human lung. Autopsy lung specimens were dissected into tissue which was cartilage free and tissue which contained cartilage. Pleura was excluded. Extraction of distal lung which did not contain cartilage by using 1.0 M NaCl and 0.5 N acetic yielded collagen having the characteristics on acrylamide gel electrophoresis and CM-cellulose chromatography of type I collagen [alpha 1(I)] alpha2. Newborn and adult type I lung collagen are similar as compared by amino acid analysis and cyanogen bromide peptide fragment analysis. Furthermore, distal lung type I collagen is very similar, if not identical, to that found in human skin. Human bronchial cartilage collagen is similar to that found in other human cartilages. Type II collagen, [alpha 1(III)], can be extracted from human distal lung using pepsin digestion and differential salt precipitation at 1.85 M sodium chloride. This distal lung type III collagen appears identical with that found in human skin. These data support the concept that normal human lung contains collagen of types I, II, and III, identical to that found elsewhere in the body. Current techniques have not revealed a unique lung collagen. This should lead to the studies which will investigate the types and ratios of the collagens in diseased human lung.

Adult↗
PubMed1975

Leukocyte recruitment to airways by cigarette smoke and particle phase in contrast to cytotoxicity of vapor.

After hamsters had breathed fresh cigarette smoke in a miniature chamber, airways of the lung showed recruitment of polymorphonuclear leukocytes. Exposure to particles alone by removal of the vapor phase with charcoal did not change the leukocyte response. However, exposure to cigarette smoke vapor after removal of particles with Cambridge filters did not recruit leukocytes but produced nuclear and cytoplasmic vacuoles, double nuclei, and exfoliation of cells.

Animals↗
PubMed1975

Responses to cotton dust.

Twelve cotton textile workers were studied: (1) to compare standard measures of volume and expiratory flow, maximal expiratory flow volume (MEFV) curves, closing volume (CV), and closing capacity (CC) in detection of airway narrowing with cotton dust exposure; (2) to evaluate the response of arterial blood gases to exposure; (3) to measure changes in leukocytes in peripheral blood and airway secretions; and (4) to assess the temporal relationships and correlations between measures. Change in expiratory flow (FEV) most consistently and significantly discriminated between the control and cotton dust exposures. Vmax50%FVC was a more sensitive indicator, but variance was increased proportionately. CV and CC changed inconsistently with relatively large variances. The PaO-2 decreased overall and two subjects had large decrements. Peripheral blood and polymorphonuclear cell counts increased with exposure to cotton dust and polymorphonuclear leukocytes were recruited to the nasal mucosa. Chest tightness and decreased flow were temporally correlated with leukocyte recruitment that may be important in respiratory disease among cotton textile workers and therefore deserves further investigation.

Adult↗