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Biomedical subjects

T W Butler

Publications and source records attributed to T W Butler.

33 records · Page 2Linked to original sources

Modulation of the development of bleomycin-induced fibrosis by deferoxamine.

Bleomycin is an antineoplastic compound which produces a time- and dose-dependent pulmonary fibrosis. The mechanisms which cause this fibrosis are not known. The ability of bleomycin to produce oxygen radicals in the presence of iron and molecular oxygen appears to be related to the fibrosis. Previous studies, which have examined single time points utilizing the ferric ion chelator deferoxamine and iron-deficient diets, suggest that iron plays a central role in bleomycin-induced pulmonary fibrosis. Therefore, the present study was designed to determine the effects of deferoxamine on the development of bleomycin-induced pulmonary fibrosis. Deferoxamine pretreatment and daily injections resulted in a significant reduction in lung collagen content and lung lipid peroxidation 21 days after intratracheal bleomycin compared with bleomycin treatment alone. In addition deferoxamine treatment significantly inhibited lung DNA increases at 4, 7, and 14 days after bleomycin treatment compared with bleomycin treatment alone. These data indicate that deferoxamine treatment reduces the development of bleomycin-induced pulmonary fibrosis in the later phase. The mechanism might be by the prevention of iron-catalyzed, free-radical formation and modulation of some cellular functions.

Animals↗

Neutrophil lactoferrin content: variation among mammals.

Lactoferrin (Lf) in blood and/or marrow neutrophils was semiquantified using indirect immunofluorescence technique in nine mammalian species. Neutrophil iron-binding reactivity (NFeBR), which corresponds primarily to Lf, was also visualized and semiquantified using functional cytochemical (FeNTA-AF) technique at the light microscopic level in these nine and in an additional fifteen mammalian species, and in selected species at the ultrastructural level. Neutrophil immunoreactive Lf was positively correlated with total cellular and granule content of NFeBR among these nine species, and with previously reported concentrations of neutrophil Lf quantified by radioimmunoassay. Relative levels of Lf in neutrophil extracts from rat, hamster, and human were confirmed using SDS-polyacrylamide gel electrophoresis and immunoblotting. Relatively high levels of immunoreactive neutrophil Lf and/or NFeBR were observed in carnivores (ten species) and primates (six species). Among rodents (five species), the levels were variable, and the artiodactyls (four species) studied had low levels. These results demonstrate that neutrophil Lf levels vary widely among mammalian species. In addition, FeNTA-AF technique provides a rapid means of evaluating animals for relative quantities of neutrophil Lf.

Animals↗

Differential staining of neutrophils and monocytes: surface and cytoplasmic iron-binding proteins.

Lactoferrin, transferrin, and ferritin were systematically visualized and semiquantified in neutrophils and monocytes/macrophages using indirect immunofluorescence and functional cytochemical techniques. They localized on cell surfaces and within the cytoplasm at the light and electron microscopical levels. In normal subjects, subpopulations of blood neutrophils and monocytes had surface lactoferrin, but little surface transferrin or ferritin was observed on these cells. Most neutrophils had brilliant granular cytoplasmic positivity for lactoferrin; variable fractions of monocytes had weak to moderate diffuse cytoplasmic lactoferrin staining localized most prominently to the cytoplasmic matrix. Most neutrophils had cytoplasmic ferritin, but few had cytoplasmic transferrin, whereas larger subpopulations of monocytes had cytoplasmic staining reactions for both proteins. To analyse maturing cells, the iron nitrilotriacetate-acid ferrocyanide method was adapted for the light microscopical analysis of neutrophils and monocytes/macrophages in soft agar culture. Further, a combined stain that visualizes iron nitrilotriacetate-acid ferrocyanide reactivity and alpha-naphthyl butyrate esterase activity in cells in blood and marrow smears was developed. The relative quantities and subcellular distribution of iron-binding proteins in neutrophils and monocytes/macrophages defined by the present methods can be correlated with biochemical, maturational, and functional properties of these cells.

Bone Marrow↗

Effect of iron deficiency on bleomycin-induced lung fibrosis in the hamster.

Bleomycin produces a dose- and time-dependent interstitial pulmonary fibrosis in humans, and is widely used to produce an animal model for the study of interstitial pulmonary fibrosis. The mechanism(s) for bleomycin-induced pulmonary fibrosis is (are) unknown, but the production of oxygen radicals by a ferrous ion-molecular oxygen pathway might be related to the fibrosis. Therefore, we studied the effect of iron deficiency on the biochemical, inflammatory, and morphologic parameters of bleomycin-induced pulmonary fibrosis in the hamster. Mild iron deficiency was induced in hamsters by bleeding via the retro-orbital sinus and maintenance on an iron-deplete diet. After intratracheal administration of bleomycin (1 U), there was no accumulation of lung collagen in the iron-deficient bleomycin-treated animals. In comparison, iron-replete animals treated with bleomycin exhibited a significant (p less than 0.01) increase in lung collagen. In addition, bleomycin-treated iron-replete animals had increased lung lipid peroxidation (p less than 0.05), whereas bleomycin-treated iron-deficient animals did not (p greater than 0.05). Lung DNA and morphometric estimates of the lesion severity were significantly increased in both iron-replete and iron-deficient bleomycin-treated animals. These data indicate that iron deficiency is associated with a reduction in the severity of bleomycin-induced pulmonary fibrosis, possibly by the prevention of iron-catalyzed oxygen-radical formation and lipid peroxidation.

Animals↗

Squamous-cell carcinoma of the anus in condyloma acuminatum. Successful treatment with preoperative chemotherapy and radiation.

A 40-year-old black male had unresectable giant condylomata acuminata of the anorectum with invasive, squamous-cell carcinoma. He was treated with intravenous 5-fluorouracil and mitomycin-C and with extended field radiation to the primary lesion. An abdominoperineal resection was performed, and the surgical specimen contained no residual cancer. Three years after diagnosis, the patient has no recurrent cancer. This case illustrates that otherwise unresectable giant condylomata acuminata with invasive carcinoma may be rendered operable with chemotherapy and radiation.

Adult↗

Eosinophilic cholangitis, lymphadenopathy, and peripheral eosinophilia: a case report.

A 32-year-old black man had nonspecific abdominal complaints and was found to have obstructive jaundice, lymphadenopathy, and eosinophilia. Eosinophilic infiltration of the cystic duct, gallbladder, lymph nodes, and bone marrow was demonstrated. The patient's symptoms, lymphadenopathy, and eosinophilia resolved spontaneously, and there was no evidence of allergy, parasitic infestation, or hypereosinophilic syndrome. A comparison of this case to other diseases in which eosinophilia and eosinophilic infiltration of one or more gastrointestinal organs occurs is presented.

Adult↗