Comparison of the protective effect of ICRF-187 and structurally related analogues against acute daunorubicin toxicity in Syrian golden hamsters.

Comparisons were made of the protective activity of ICRF-187 and a series of related bis-dioxopiperazine analogues against acute daunorubicin toxicity in Syrian golden hamsters. A single dose of daunorubicin (25 mg/kg) caused a marked decrease in body weight and was lethal to 84% of the animals within 1 to 4 weeks. Pretreatment with ICRF-187, the d-isomer of ICRF-159, ameliorated the lethal effects of daunorubicin.

Influence of the diabetic state on isoproterenol-induced cardiac necrosis.

Isoproterenol-induced myocardial necrosis was examined in male mice with alloxan-induced and genetically transmitted diabetes. Ten days after alloxan treatment, mice exhibited an elevation in blood glucose concentrations, weight loss, polyuria and decreased heart rates (510 +/- 15 v. 675 +/- 11 beats/min) compared with matched control mice.

Transcatheter ablation: comparison between laser photoablation and electrode shock ablation in the dog.

To characterize and compare the effects of transcatheter laser and electrical energy on endocardium, 35 laser pulses were delivered to the endocardial surfaces of isolated canine hearts, and 33 endocardial lesions were produced by the transarterial delivery of either transcatheter laser irradiation or electrical shock in closed-chest anesthetized dogs. Laser-induced lesion dimensions in vitro and in vivo increased with increased total dose of energy; however, the lesions produced in vivo were different in morphology and were significantly larger than lesions produced by equivalent doses of energy delivered in vitro (p less than .05).

Patterns of pulmonary structural remodeling after experimental paraquat toxicity. The morphogenesis of intraalveolar fibrosis.

For a study of the evolution of interstitial and intraalveolar fibrosis, ultrastructural and immunohistochemical observations were made of the lungs of 16 cynomolgous monkeys given 1 or 2 injections of 10 mg/kg of paraquat and sacrificed 2 days to 8 weeks later. At 2-3 days, alveolar epithelial cells were denuded in many areas, and fibronectin was conspicuous in alveolar spaces. At 1 week, fibroblasts and inflammatory cells were migrating through gaps in the denuded epithelial basement membranes; Type II cells were regenerating in some areas.

Immunocytochemical characterization of pulmonary histiocytosis X cells in lung biopsies.

Morphologic and immunohistochemical studies were made of open lung biopsies from 9 patients with pulmonary histiocytosis X (HX) and 12 patients with other conditions, and of skin biopsies from patients with cutaneous sarcoidosis, Chester-Erdheim disease, and eruptive histiocytoma. The monoclonal antibody OKT6 was detected with the use of goat anti-mouse IgG labeled with fluorescein (FITC) for light microscopy, and sheep antimouse Fab'2 fragment of IgG labeled with horseradish peroxidase (HRP) for immunoelectron microscopy. The presence of S-100 protein was revealed by an antibody prepared against bovine S-100 protein, using sheep anti-rabbit IgG labeled with FITC for light microscopy and with HRP for immunoelectron microscopy.

Poikilocytosis in dogs with chronic doxorubicin toxicosis.

Peripheral blood smears made during 2 studies of chemical antidotes for doxorubicin (DRB) cardiotoxicity in dogs were examined to determine the incidence of poikilocytosis. The 1st study had significantly (P less than 0.05) increased numbers of poikilocytes in 3 groups of 5 dogs, each treated with DRB alone, DRB plus thyroxine (0.

Motheaten mice--an animal model with an inherited form of interstitial lung disease.

The motheaten gene represents a single recessive mutation that occurs in mice and is associated with systemic immune abnormalities. Although they have abnormalities in several organs, homozygote animals (me/me) die by 8 wk of age from a diffuse, noninfectious lung disease. To evaluate this genetically determined model of interstitial lung disease, the lungs of these animals were studied by light and transmission electron microscopy and by bronchoalveolar lavage.

Experimental polymyxin B-induced interstitial lung disease characterized by an accumulation of cytotoxic eosinophils in the alveolar structures.

A variety of lung disorders are associated with the accumulation of eosinophils in the alveolar structures. To help understand the role of eosinophils in these disorders, an animal model of eosinophilic lung disease was developed. Administration of an aerosol of polymyxin B to guinea pigs (3 times per wk for 4 wk) produced diffuse interstitial lung disease with alveolar wall thickening and an alveolitis characterized by marked increases in eosinophils and alveolar macrophages.

Characterization of mononuclear phagocyte subpopulations in the human lung by using monoclonal antibodies: changes in alveolar macrophage phenotype associated with pulmonary sarcoidosis.

Current concepts of pulmonary sarcoidosis suggest that the alveolar macrophage plays a central role in the pathogenesis of the disease. To help define the population of alveolar macrophages in sarcoidosis, we compared the surface phenotype of alveolar macrophages from patients with sarcoidosis and from normal individuals by using monoclonal antibodies (63D3, OKM1, M phi P-9, M phi S-1, 61D3, and M phi S-39) that detect surface antigens on cells of monocyte/macrophage lineage. Although almost all blood monocytes expressed surface antigens detected by each of these antibodies, only a minority of normal alveolar macrophages expressed the same surface antigens (p less than 0.

Comparison of the effectiveness of (+/-)-1,2-bis(3,5-dioxopiperazinyl-1-yl)propane (ICRF-187) and N-acetylcysteine in preventing chronic doxorubicin cardiotoxicity in beagles.

This investigation examined the potential of N-acetylcysteine (NAC) and ICRF-187, alone and in combination, to protect against chronic doxorubicin cardiotoxicity. Adult beagles of either sex (7.3 to 12.

Granulomatous inflammation of the heart.

Morphologic characteristics of granulomatous inflammation in the heart and pericardium are discussed. In rheumatic fever, two types of myocardial lesion are present--a nonspecific myocarditis and a specific lesion characterized by granulomas known as Aschoff's nodules. The latter undergo a cycle of development and resolution; in their mature stage, they contain Aschoff's cells which are uni- or multinucleated histiocytes with a serrated nuclear chromatin bar.

Cardiovascular lesions in collagen-vascular diseases.

In this review, the cardiac lesions which develop in association with the various collagen-vascular diseases are described. In rheumatoid arthritis, the most frequent lesions are: fibrous obliterative pericarditis, with pericardial deposits of calcium, fibrin, cholesterol, and rheumatoid granulomas; granulomatous or nonspecific myocarditis; valvulitis, vasculitis, and amyloid deposits. In ankylosing spondylitis, the lesions involve mainly the valves (aortic and mitral valves) and the aorta.

Cardiac lesions of selenium-vitamin E deficiency in animals.

Necrosis of myocardium and skeletal muscle is a consistent finding in the numerous animal species in which spontaneous or experimental selenium-vitamin E (Se-E) deficiency has been described. Etiologic factors in the development of these lesions include: low dietary levels of Se, vitamin E, and sulfur-containing amino acids; high dietary concentrations of polyunsaturated fats; exposure to prooxidant conditions (toxicity by O2, O3, Fe, doxorubicin, and radiation injury); and intake of Se antagonists (Ag, Cu, Co, Cd, Te, Sb, and Zn). Myocardial lesions in Se-E deficient animals are most frequently seen in calves, lambs, turkey poults, and ducklings.

DNA synthesis in rat atrial myocytes as a response to left ventricular infarction. An autoradiographic study of enzymatically dissociated myocytes.

An autoradiographic study was performed on enzymatically isolated atrial muscle cells to examine the DNA synthetic response of atria to left ventricular infarction. DNA synthesis was studied in left and right atrial myocytes and nonmyocytes of: young Sprague-Dawley rats 11 days after ligation of the left coronary artery; rats subjected to a sham surgical procedure without coronary artery ligation; unoperated rats. Each animal received a series of ten injections of tritiated thymidine at 12-h intervals, beginning on the fifth post-operative day; cells were isolated 36 h after the last injection.

Accurate quantification of cells recovered by bronchoalveolar lavage.

Quantification of the differential cell count and total number of cells recovered from the lower respiratory tract by bronchoalveolar lavage is a valuable technique for evaluating the alveolitis of patients with inflammatory disorders of the lower respiratory tract. The most commonly used technique for the evaluation of cells recovered by lavage has been to concentrate cells by centrifugation and then to determine total cell number using a hemocytometer and differential cell count from a Wright-Glemsa-stained cytocentrifuge preparation. However, we have noted that the percentage of small cells present in the original cell suspension recovered by lavage is greater than the percentage of lymphocytes identified on cytocentrifuge preparations.

Alveolar macrophage replication. One mechanism for the expansion of the mononuclear phagocyte population in the chronically inflamed lung.

Within any chronically inflamed tissue, there is an increased number of macrophages, pluripotential phagocytic cells that, while critical to host defenses, are also able to profoundly damage parenchymal structure and function. Because of their central role in the inflammatory response, considerable attention has been focused on the mechanisms resulting in an expansion of the macrophage population within an inflamed tissue. Although recruitment of precursor monocytes from the circulation into inflamed tissues clearly plays an important role in macrophage accumulation, it is also possible that replication of tissue macrophages contributes to the expansion of macrophage numbers in inflammation.

Development of elastic fibers of nuchal ligament, aorta, and lung of fetal and postnatal sheep: an ultrastructural and electron microscopic immunohistochemical study.

The morphogenesis of elastic fibers of the nuchal ligament, aorta, and lung of sheep was studied by light microscopy, transmission electron microscopy, and immunohistochemical methods for the detection of elastin. The degree of maturation of the amorphous materials of elastic fibers was assessed morphologically in preparations stained by the tannic acid and periodic acid methenamine-silver methods. With both of these methods, the amorphous components of mature fibers stained less intensely than did those of immature fibers.

Cardiac morphologic alterations in acute minoxidil cardiotoxicity in miniature swine.

Minoxidil, a vasodilating antihypertensive drug, was given orally at 10 mg/kg daily for 2 days to twelve 25- to 35-kg miniature pigs. Twelve control pigs were also studied. Minoxidil-treated pigs had tachycardia and hypotension and were killed 24 hr after the second dose.

Role of pleural mesothelial cells in the production of the submesothelial connective tissue matrix of lung.

The pleura is comprised of a single layer of mesothelial cells resting on a complex layer of connective tissue. The ability of mesothelial cells to produce the components of this connective tissue was investigated using cultured rat mesothelial cells. These cells produced several components of extracellular matrix, including 6.

The electron microscopic immunohistochemistry of elastase-treated aorta and nuchal ligament of fetal and postnatal sheep.

In conjunction with the immunoperoxidase and the immunoferritin methods, antielastin antibody was used to study the localization of elastin in untreated and elastase-treated elastic fibers of the nuchal ligament and the aorta of fetal and young adult sheep. In tissues not treated with elastase, the staining reaction for antielastin antibody was localized in the outer zones of the amorphous components and along the surfaces of the microfibrils ; the central zones of the amorphous components were unreactive. After mild elastase treatment, incompletely digested amorphous components showed staining both in their central and outer zones, and some of the microfibrils became unreactive.

Modification by the Hancock T6 process of calcification of bioprosthetic cardiac valves implanted in sheep.

The effectiveness of the T6 process (surfactant treatment) to decrease calcification of porcine aortic valvular (PAV) and bovine pericardial (BPV) bioprostheses was investigated. Morphologic and biochemical studies were made of standard and T6-treated PAVs and BPVs that had been implanted for a mean of 20 weeks in the tricuspid position in young sheep. Gross, radiographic, histologic and ultrastructural observations showed that the calcific deposits were less severe in T6-treated (n = 9) than in standard PAVs (n = 7), but were similar in severity in T6-treated (n = 6) and standard BPVs (n = 7).

Hereditary emphysema in the tight-skin mouse. Evaluation of pathogenesis.

The tight-skin (Tsk/+) mouse is a genetically determined model characterized by alveolar enlargement and physiologic evidence of emphysema. Morphologic evaluation of the lungs of these animals demonstrated increased numbers of potential protease-secreting cells (alveolar macrophages and neutrophils) in the lower respiratory tract prior to development of the emphysematous lesions. Quantitation of the neutrophils in the lungs of these animals was carried out by bronchoalveolar lavage.

Diagnosis of pulmonary histiocytosis X by immunodetection of Langerhans cells in bronchoalveolar lavage fluid.

Based on the finding that Langerhans cells and histiocytosis X cells react with the monoclonal antibody OKT6, raised against a subset of thymocytes, we used this antibody to study the cells collected by bronchoalveolar lavage (BAL) from 131 patients, including 18 with pulmonary histiocytosis X, 43 with pulmonary sarcoidosis, 67 with miscellaneous pulmonary disorders, and 3 controls. Immunofluorescence studies demonstrated the presence of OKT6-reactive cells in all patients with pulmonary histiocytosis X (mean +/- SEM, 5.29% +/- 1.

Toxic interactions of benzyl alcohol with bacterial endotoxin.

Acute toxic interactions of intravenously administered benzyl alcohol and Escherichia coli O55:B5 (Boivin preparation) endotoxin were examined in rodents. Lethality studies in male CD-1 mice demonstrated that these agents were more toxic when administered in combination than when either was administered alone. Prophylactic treatment with diazepam (5 mg/kg intraperitoneally) protected against lethality induced by either the combination or the endotoxin yet offered little, if any, protection against the lethal effects of benzyl alcohol.