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Biomedical subjects

V J Ferrans

Publications and source records attributed to V J Ferrans.

At least 307 records · Page 17Linked to original sources
PubMed1981

Reduction of chronic daunorubicin cardiotoxicity by ICRF-187 in rabbits.

To determine whether ICRF-187 (NSC-169780) would alter chronic daunorubicin (NSC-82151) cardiac toxicity, male New Zealand rabbits were given 3.2 mg/kg or daunorubicin iv alone or 30 minutes after 12.5 or 25.0 mg/kg of ICRF-187 ip at 3-week intervals. Control rabbits received either saline iv or ICRF-187 (12.5 or 25.0 mg/kg) ip on the same schedule. Three weeks after the fifth injection, the animals were sacrificed. The frequency and extent of cellular alterations were graded on a scale of 0 to 4. Lesions consisting mainly of vacuolization and myofibrillar loss were noted in the hearts of all 12 rabbits given daunorubicin alone. The severity ranged from 1 to 3 (average 1.8). In contrast, no abnormalities were noted in one of five (12.5 mg/kg) and three of seven (25.0 mg/kg) ICRF-treated rabbits. The remaining eight hearts from both pretreatment groups displayed animal alterations ranging from 0.5 to 1.0 (average 0.9). Thus, concurrent administration of the antineoplastic agent ICRF-187 may offer a means of reducing chronic daunorubicin cardiac toxicity.

Animals↗
PubMed1981

Reduction of chronic doxorubicin cardiotoxicity in dogs by pretreatment with (+/-)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane (ICRF-187).

Adult beagle dogs were given doxorubicin (1.0 mg/kg body weight i.v.) either alone or 30 min after ICRF-187 (NSC 169780) (12.5 mg/kg body weight i.p.) at weekly intervals. Control dogs received 0.9% NaCl solution i.v. 30 min after ICRF-187 i.p. (12.5 mg/kg body weight). One week after the 15th injection (300 mg/sq m total dose), the animals were sacrificed. The frequency and extent of cellular lesions were graded on a scale of 0 to 4+. Such lesions, consisting mainly of vacuolization and myofibrillar loss, were noted in the hearts of all six dogs given doxorubicin alone. The lesions were severe (4+) in five of these animals and moderate (2+) in one. In contrast, no abnormalities were noted in the hearts of four of the six dogs pretreated with ICRF-187 before doxorubicin administration; the remaining two animals in this group had minimal alterations (1+). At the dosage regimen used in the present experiments, doxorubicin did not induce lesions in lungs, liver, kidney, diaphragm, small intestine, or skeletal muscles. Comparable decreases in white blood cell count, red blood cell count, hemoglobin, and serum iron concentration were found in animals receiving doxorubicin with or without ICRF-187. Concurrent administration of ICRF-187 offers a promising means of reducing the chronic cardiotoxicity induced by doxorubicin.

Animals↗
PubMed1981

Pulmonary Langerhans' cells in patients with fibrotic lung disorders.

Langerhans' cells were found in lung biopsies in one of nine control patients and in 20 of 160 patients with fibrotic lung disorders, including 13 of 56 patients with idiopathic pulmonary fibrosis, two of nine patients with collagen vascular diseases, two of seven patients with hypersensitivity pneumonitis, and each of three patients with end stage fibrosis of uncertain cause. Langerhans' cells were not found in any of the 41 patients with sarcoidosis, the 35 patients with interstitial lung diseases associated with inhalation of inorganic dusts, the seven patients with pulmonary lymphangioleiomyomatosis, or the two patients with chronic eosinophilic pneumonia. In the control patient, Langerhans' cells were found between epithelial cells in bronchioles. In patients with fibrotic lung disorders, Langerhans' cells were found in the epithelial layer of bronchioles and alveoli containing proliferating epithelial cells, i.e., either cuboidal epithelial cells of bronchiolar origin or type II alveolar epithelial cells. Severe fibrosis or squamous metaplasia were not prerequisites for the presence of Langerhans' cells. The motility of Langerhans' cells apparently was restricted, as they were not found in the air spaces in any of the biopsies, and they were not recovered from bronchoalveolar lavage fluid of any of the 97 patients studied, even though some of these patients had relatively numerous Langerhans' cells in lung biopsies. These observations are in sharp contrast to those in pulmonary histiocytosis X, in which histiocytosis X cells (HX cells) occur in granulomas, in alveolar interstitium, and between epithelial cells of the lower respiratory system. HX cells also migrate into air spaces, as shown by their occurrence in bronchoalveolar lavage fluid. The HX bodies in HX cells are morphologically similar to Langerhans' cell granules, but are more numerous and pleomorphic. HX cells are considered to be reactive or activated Langerhans' cells.

Alveolitis, Extrinsic Allergic↗
PubMed1981

Reduction in the diabetogenic effect of alloxan in mice by treatment with the antineoplastic agent ICRF-187.

Blood glucose concentrations were markedly elevated in CD-1 mice 48 hr after iv administration of alloxan (75 mg/kg). Treatment with three doses of ICRF-187 (96 to 345 mg/kg) given 60 min before and 4 and 8 hr after alloxan significantly attenuated the increase in blood glucose. Pretreatment with dimethyl sulfoxide (DMSO), a known free radical scavenger, at doses of 3.5 to 7.3 g/kg also protected against the alloxan diabetogenic action. When the lowest doses of ICRF-187 (96 mg/kg) and DMSO (3.5 g/kg) were combined, alloxan exerted no hyperglycemic effect. The protective effects of ICRF-187 and DMSO were confirmed morphologically. In alloxan-treated animals, beta cell granules were absent. In contrast, the degree of granulation showed only a mild to moderate reduction in those alloxan-treated animals given ICRF-187 alone, DMSO alone, or the combination of ICRF-187 and DMSO. These results suggest that ICRF-187 may alter the mechanism of free radical generation thought to be responsible for the production of alloxan diabetes.

Alloxan↗
PubMed1981

Structure of bovine parietal pericardium and of unimplanted Ionescu-Shiley pericardial valvular bioprostheses.

To obtain a basis for the evaluation of postimplantation changes in bioprostheses made of parietal pericardium, we conducted comparative histologic, scanning and transmission electron microscopic studies of the structure of (1) normal bovine parietal pericardium, (2) glutaraldehyde-treated pericardial patches to be used for repair of cardiac defects, and (3) pericardial tissue cusps of unimplanted Ionescu-Shiley valves. Bovine parietal pericardium has three layers: (1) the serosa, or mesothelial cell layer; (2) the fibrosa, formed by diversely oriented, wavy bundles of collagen and by elastic fibers, and (3) the epipericardial connective tissue layer, which is partly continuous with the pericardiosternal ligaments. Pericardial patches and pericardial bioprosthetic cusps differ from normal pericardium by being denuded of mesothelium but they have normal degrees of waviness in their collagen. In Ionescu-Shiley valves, the inflow and outflow surfaces of each cusp correspond to the epipericardial and serosal surfaces of parietal pericardium, respectively. The inflow surfaces have a coarse texture, characterized by large bundles of collagen, and the outflow surfaces have numerous grooves, 10 to 30 mu in width and 20 mu in depth, which probably result from pressure exerted on the cuspidal surfaces by cotton material either during manufacturing or packing of the valves. Comparisons of the structure of bioprosthetic pericardial cusps and porcine aortic valve cusps show that the latter have reduced degrees of collagen waviness and a different layered structure: A layer similar to the spongiosa of aortic valve cusps is not present in pericardium. The functional implications of these observations are discussed in detail.

Animals↗
PubMed1981

Cardiotoxicity associated with high-dose cyclophosphamide therapy.

The cardiac effects of chemotherapeutic regimens using high doses of cyclophosphamide (180 mg/kg over four days) were assessed in 32 patients with hematologic malignant neoplasms. Left ventricular systolic function, determined by the fractional shortening on echocardiogram, declined substantially five to 16 days after the initiation of cyclophosphamide therapy. Although pericardial effusion on echocardiogram occurred in 33% of the patients studied, ECG voltage decreased five to 14 days after beginning cyclophosphamide therapy even in those patients without pericardial effusion. Congestive heart failure was noted in nine patients (28%) within three weeks of cyclophosphamide administration. Six of these patients (19%) died of myocardial failure. Pericardial tamponade occurred in six patients (19%), including five who died of myocardial failure. Histopathologic and electron microscopic findings showed endothelial injury and a hemorrhagic myopericarditis. Cyclophosphamide in this high dose is associated with a toxic, often fatal, pericardiomyopathy. Depression of ECG voltage and systolic left ventricular function, though common, do not necessarily predict clinical cardiac deterioration.

Adolescent↗
PubMed1981

Induction of lesions of selenium-vitamin E deficiency in weanling swine fed silver, cobalt, tellurium, zinc, cadmium, and vanadium.

Forty-two weanling pigs were allotted to 7 groups and fed (for 10 weeks) a commercial ration that was adequate in selenium and vitamin E (Se-E) content, either alone or with supplements of Ag (3,000 mg/kg of feed, as acetate), Co (500 mg/kg, as chloride), Te (500 mg/kg, as tetrachloride), Zn (3,000 mg/kg, as sulfate), Cd (500 mg/kg, as sulfate), or V (200 mg/kg, as vanadate). The pigs fed the Ag supplement died after 25 to 39 days and had lesions characteristic of Se-E deficiency with accumulations of serous transudates in body cavities and hepatic and cardiac necrosis. In the pigs fed the Ag supplement, there was high hepatic Se content terminally; blood glutathione peroxidase (GSH-Px) activity decreased to low levels several weeks before the pigs died with lesions of Se-E deficiency. Macroscopic lesions of Se-E deficiency were not found in pigs fed Co, Te, Zn, Cd, or V. However, evidence of Se-E deficiency, as indicated by microscopically detected necrosis of cardiac and skeletal muscle, was present in 50% to 65% of the pigs fed Co or Te and occasionally in pigs fed Zn, Cd, and V supplements. The pigs fed Te had marked decrease of blood GSH-Px activity over the last 6 weeks of the feeding period. No consistently abnormal values for blood GSH-Px activity or terminal hepatic Se content were observed in pigs fed Co, Zn, Cd, or V. The pigs fed the Zn supplement grew as rapidly as the control pigs. Evidence of V toxicosis was observed as severe growth suppression, mortality, and marked enteritis and cystitis (with accompanying hydroureter in 1 pig).

Animals↗
PubMed1981

Pathologic alterations in congestive cardiomyopathy of dogs.

Eleven large-breed dogs with congestive cardiomyopathy were studied at necropsy. Seven of 11 dogs were Great Dane and 9 of 11 were male. The most common clinical signs in affected dogs were dyspnea, abdominal distention by ascites, and weight loss. Three dogs had severe congestive cardiac failure. At necropsy, gross alterations in the hearts were cardiomegaly, dilation of all chambers, opacity of the endocardium, atrial thrombosis, and disseminated foci of myocardial necrosis. Extracardiac changes included hepatic congestion, pulmonary congestion and edema, ascites, and infarction of kidney, liver, lung, and spleen. Microscopically, the affected hearts had disseminated foci of subendocardial myocardial necrosis, scattered areas of myocardial fibrosis, and medial hyperplasia of intramyocardial arteries. Ultrastructurally, degenerated cardiac muscle cells had myocytolysis, proliferated elements of sarcoplasmic reticulum, numerous myelin figures and autophagic vacuoles, large numbers of lipofuscin granules, and mitochondrial alterations. These ultrastructural alterations are similar to those described for cardiomyopathy in persons and cats.

Animals↗
PubMed1981

Induction of lesions of selenium-vitamin E deficiency in ducklings fed silver, copper, cobalt, tellurium, cadmium, or zinc: protection by selenium or vitamin E supplements.

In 3 experiments, 684 newly hatched White Pekin ducklings were fed (for 15 to 28 days) a commercial starter mash that was adequate in selenium and vitamin E (Se-E) content, either alone or with supplements of Ag (3,000 mg/kg of feed, as acetate), Cu (1,500 mg/kg, as sulfate), Co (200 or 500 mg/kg, as chloride), Te (500 mg/kg, as tetrachloride), Cd (100 or 500 mg/kg, as sulfate), Zn (3,000 or 6,000 mg/kg, as sulfate), or V (100 mg/kg, as vanadate). The ducklings fed Ag, Cu, Co, Te, Cd, and Zn frequently developed lesions characteristic of Se-E deficiency, such as necrosis of skeletal and cardiac muscle and of smooth muscle of the gizzard and intestine. Complete protection from the muscle lesions produced by Cu, Co, Te, Cd, and Zn supplements was provided by vitamin E (200 IU of alpha-tocopherol acetate/kg) and Se (2 mg/kg, as selenite). Ducklings fed Ag were protected by supplements of vitamin E and partial protection was achieved by Se addition. The birds fed excessive Zn developed pancreatic necrosis and fibrosis that was not prevented by supplements of Se or vitamin E. Terminally, blood glutathione peroxidase activity was low and hepatic Se concentration was increased in the ducklings fed Ag. However, neither blood glutathione peroxidase activity nor hepatic Se concentrations was consistently abnormal in ducklings fed other trace elements, although lesions of Se-E deficiency were often present in these animals.

Animals↗
PubMed1980

Maintenance of granuloma formation in pulmonary sarcoidosis by T lymphocytes within the lung.

Pulmonary granulomata of sarcoidosis are composed primarily of mononuclear phagocytic cells that are probably derived from blood monocytes. To evaluate the concept that recruitment of blood monocytes to the sarcoid lung is mediated by chemoattractants produced by immune effector cells within the lung, we obtained mononuclear cells from lung and blood of six patients with active pulmonary sarcoidosis, six normal subjects, and six patients with active idiopathic pulmonary fibrosis and studied their ability to secrete a chemotactic factor for monocytes. Lung T lymphocytes from all sarcoidosis patients, but not from normal subjects or patients with idiopathic pulmonary fibrosis, spontaneously secreted such a mediator. Lung T lymphocytes from patients with sarcoidosis secreted more monocyte chemotactic factor than did blood T lymphocytes from the same patients. The accumulation of monocytes in the lung in patients with pulmonary sarcoidosis may be mediated by local production of monocyte chemotactic factor by lung T lymphocytes.

Adult↗
PubMed1980

Histologic and ultrastructural features of normal human parietal pericardium.

Morphologic studies of normal anterior parietal pericardium from seven patients revealed this tissue to be composed of three layers: (1) the serosa, consisting of a surface layer of mesothelial cells and a narrow submesothelial space, (2) the fibrosa, containing variously oriented layers of collagen fibrils and small elastic fibers, and (3) the epipericardial connective tissue layer, containing mainly large coarse bundles of collagen and forming part of the pericardiosternal ligament. Scanning electron microscopic examination is most useful for study of the surface features of pericardial mesothelial cells, which have single cilia and are covered with microvilli. The latter bear friction and increase the surface area for fluid transport. Junctional complexes between adjacent mesothelial cells consist of desmosomes, which reinforce intercellular adhesion and zonulae occludentes, which form permeability barriers. Actin-like filaments (50 A in diameter) are present in microvilli and in immediately subjacent regions of the cells; these filaments mediate changes in cell shape. Intermediate filaments (100 A in diameter) are associated with desmosomes and form bundles in the perinuclear regions; these filaments provide structural support to the cytoplasm.

Adolescent↗
PubMed1980

Chronic airflow obstruction in Fabry's disease.

Seven patients with Fabry's disease, an x-linked sphingolipid storage disorder, were evaluated for the presence and extent of airway obstruction. All were found to have significant obstruction to airflow. In addition, evaluation of their airway epithelial cells obtained by bronchoscopy demonstrated that these cells contained inclusion bodies consistent with deposits of ceramide trihexoside, suggesting that part of their functional obstruction to airflow may be secondary to intrinsic airway disease. Although all of the study population had evidence of airflow obstruction, the impairment was much worse in those who smoked, implying that even mild cigarette smoking is particularly hazardous to patients with Fabry's disease.

Adult↗
PubMed1980

Collagen concentration and rates of synthesis in idiopathic pulmonary fibrosis.

To define the biochemical correlates of the apparent morphologic increase in lung interstitial collagen in idiopathic pulmonary fibrosis (IPF), collagen content was quantitated, and the morphologic degree of fibrosis was assessed in 9 patients with IPF and 6 control subjects. There were no significant differences in the collagen content among patients with IPF compared with that of control subjects. In addition, there was no correlation between collagen content and the morphologic assessment of the degree of fibrosis. Analysis of the collagen content from multiple sites made from base to apex of postmortem material from 3 patients with IPF and 2 control subjects demonstrated a wide, but similar, variation in collagen content in both groups; no definite pattern of anatomic distribution was found in either the patients with IPF or the control subjects. Furthermore, the rates of collagen and noncollagen protein synthesis in explants of lung of patients with IPF demonstrated no significant differences compared with those of the control subjects. The results of this study are consistent with the concept that IPF is a disease of an alteration in quality, form, and location of collagen rather than simply a disease of increased interstitial collagen.

Adult↗