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Biomedical subjects

V J Ferrans

Publications and source records attributed to V J Ferrans.

At least 325 records · Page 18Linked to original sources
PubMed1980

Subplasmalemmal linear densities in cells of the mononuclear phagocyte system in lung.

The presence of subplasmalemmal linear densities in cells of the mononuclear phagocyte system was investigated in pulmonary biopsies from 33 patients with fibrotic lung disorders. Subplasmalemmal linear densities, consisting of a thin layer of electron-dense material immediately subjacent to the inner leaflet of the plasma membrane, were found in 30 of the 33 patients, including each of 6 patients with pulmonary sarcoidosis, 18 of 19 patients with idiopathic pulmonary fibrosis, 4 of 5 patients with collagen-vascular diseases, 1 patient with pulmonary lymphangioleiomyomatosis, and 1 patient with marked interstitial pulmonary fibrosis associated with squamous cell carcinoma of the lung. Subplasmalemmal linear densities were found in epithelioid cells, macrophages, and giant cells in granulomas in the 6 patients with sarcoidosis and in alveolar macrophages in 4 of these patients. In patients with other fibrotic lung disorders, subplasmalemmal linear densities were limited in distribution to interstitial and alveolar macrophages. In all patients with sarcoidosis some of the subplasmalemmal linear densities of adjacent mononuclear phagocytes, particularly of those in granulomas, were paired and formed specialized intercellular junctions. Such junctions also were observed in macrophages in 10 of the patients with other fibrotic lung disorders. The junctions formed by subplasmalemmal linear densities differed from other types of junctional structures. Subplasmalemmal linear densities appear to function in 1) the binding of action filalar junctions, which may contribute to the immobilization of mononuclear phagocytes in granulomas and alveolar lumens.

Actinin↗
PubMed1980

Pathologic alterations in hypertrophic and congestive cardiomyopathy of cats.

Pathologic alterations were studied in 15 cats with cardiomyopathy. Ten of these had hypertrophic cardiomyopathy, characterized by cardiomegaly, diffuse myocardial hypertrophy, small left ventricular cavities, and dilated left atria; the ventricular septum and left ventricular free walls were thick, but asymmetric septal hypertrophy was not present. Aortic thromboembolism, renal infarction, and pulmonary congestion and edema were frequent. Histopathologic and ultrastructural study revealed hypertrophy and disarray of cardiac muscle cells (most severe in left ventricle and ventricular septum), interstitial fibrosis, and fibromuscular hyperplasia of small intramural coronary arteries. The hypertrophied fibers had large nuclei, prominent Golgi complexes, and numerous polysomes; some fibers had crisscrossing myofibrils. Degenerative alterations in hypertrophied myocytes were: perinuclear distension of elements of sarcoplasmic reticulum, focal myofibrillar lysis, numerous thick clumps of Z-band material, and abundant lipofuscin granules. The interstitium showed accumulations of collagen fibrils, increased numbers of fibroblasts, and scattered remnants of external lamina. One cat had dilated chambers, but also had typical histologic and ultrastructural alterations of hypertrophic cardiomyopathy and was considered to have a late stage of this disorder. Four cats had congestive cardiomyopathy, with cardiomegaly and dilatation of all chambers. Hydrothorax and pulmonary congestion and edema were generally present. Cardiac histopathologic and ultrastructural alterations consisted only of mild interstitital edema and fibrosis. Detailed comparisons reveal many similarities in the spectrum of morphologic features of hypertrophic cardiomyopathy in human beings and cats; there are not marked differences in the morphologic features of congestive cardiomyopathy in human beings and cats. Thus, cardiomyopathies in the cat constitute useful models for the study of these diseases in human beings.

Animals↗
PubMed1980

Cardiac disease induced by chronic adriamycin administration in dogs and an evaluation of vitamin E and selenium as cardioprotectants.

Chronic adriamycin (ADR) intoxication was produced in three groups of beagle dogs by weekly intravenous injections (1 mg/kg body weight) for 20 weeks (cumulative dose 400 mg/sq m). Group A (6 dogs) received ADR only; Group B (6 dogs) were given ADR and weekly doses of vitamin E (17 mg/kg body weight) as alpha-tocopherol acetate; and Group C (6 dogs) received ADR and weekly doses of vitamin E as did Group B and selenium (0.06 mg/kg body weight as selenite). Each of the 18 dogs developed ADR-induced cardiomyopathy (CMY), and death occurred in 11 dogs during Weeks 17-20. Mortality was lowest in Group B (2 of 6), but no differences between groups were seen either in survival time of the dogs that died or in severity of CMY. Cardiomyopathy was more severe in dogs that died than in survivors. Congestive heart failure with transudation was present in 4 of 11 dogs that died. Cardiac histopathology was characterized by vacuolar degeneration of myocytes. Myocardial damage was most severe in the left ventricle and the ventricular septum, intermediate in the right ventricle and the left atrium, and least in the right atrium. Ultrastructural study showed that an early alteration in damaged myocytes was distention of sarcoplasmic reticulum to form sarcoplasmic vacuoles. Occasional damaged fibers had myofibrillar lysis and focal proliferation of sarcoplasmic reticulum. This study demonstrates that the dog offers a suitable model for studies of chronic ADR cardiotoxicity in man. The lack of cardioprotection from vitamin E and selenium supplementation fails to support the proposed role of lipoperoxidative damage in the development of chronic ADR-induced CMY.

Animals↗
PubMed1980

Clinical observations, cutaneous lesions, and hematologic alterations in chronic adriamycin intoxication in dogs with and without vitamin E and selenium supplementation.

Chronic adriamycin (ADR) intoxication with cardiomyopathy developed in young Beagle dogs given weekly IV injections (1 mg/kg of body weight) for 20 weeks (cumulative dose 400 mg/m2). Eighteen dogs were allotted equally to three groups: group A received ADR only, group B was given ADR and simultaneous weekly doses of vitamin E (17 mg/kg of body weight as alpha-tocopherol acetate), and group C received ADR, weekly doses of vitamin E as in group B, and selenium (0.06 mg/kg of body weight as selenite). The dogs reacted with cutaneous hyperemia, head shaking, and vomiting immediately after ADR injection. After 4 to 6 weekly injections, all the dogs developed alopecia that was present initially over the head and subsequently extended to the ventral portions of the neck, thorax, and abdomen and the proximal inner areas of the limbs. Other skin lesions present in alopecic areas were secondary ulcerative dermatitis and melanosis. Testicular atrophy and cachexia developed in the dogs, but damage was not present in bone marrow, alimentary tract, kidney, and bone with the dosage schedule utilized. Hematologic studies showed no significant alterations. Supplementation with vitamin E alone or with selenium failed to alter the incidence and severity of extracardiac ADR-induced lesions. This study shows that the dog is a good model for studies of chronic ADR-induced cardiotoxicity, as cardiac damage was consistently produced and ADR-associated extracardiac lesions were of minimal severity.

Alopecia↗
PubMed1980

Optimal preparation techniques for human saphenous vein grafts.

Endothelial damage during preparation of saphenous vein grafts is an important cause of early and late graft failure. To determine optimal preparation techniques for human saphenous veins (SVs), we made a scanning electron microscopic comparison of the effects of handling techniques, immersion media, and distention pressures on human SV morphology. Segments of SVs from 30 patients were divided into seven groups of five veins each. The effects of both blood and saline solution immersion at 4 degrees and 28 degrees C, 100 and 300 mm Hg distention pressures, and trauma from surgical instrumentation were examined. All groups of veins were fixed by perfusion with glutaraldehyde at 100 mm Hg to simulate arterial pressure and were examined with a scanning electron microscope. SVs immersed in warm saline solution showed massive endothelial cell loss, whereas SVs immersed in warm blood showed only moderate endothelial damage. Cold blood and saline immersion fully preserved endothelium; however, cold saline immersion produced mural edema. Distention to 300 mm Hg with saline solution produced severe endothelial damage and edema, an effect lessened by blood distention. Vascular clamping destroyed endothelium and fractured the intima and media. Marked luminal stenoses were caused by four of seven side branch ties that appeared normal externally. We conclude that human SVs are preserved best by a "no touch" harvesting technique in which manipulation is minimized, side branch ties are placed away from the SV wall, veins are immersed in cold blood, and distention above 100 mm Hg is avoided.

Blood↗
PubMed1980

Clinical and pathologic features of chronic adriamycin toxicosis in rabbits.

Chronic adriamycin (ADR) intoxication was produced in 50 weanling rabbits by weekly injections of ADR (2.4 mg/kg of body weight) for up to 17 weeks. All ADR-treated rabbits developed prominent alopecia, edema, moderate anemia, and severe emaciation. The frequency and severity of cardiomyopathy were not strongly dose-related, but renal lesions were. The frequency and severity of cardiomyopathic lesions were highest in left ventricular free wall and ventricular septum, intermediate in atria, and lowest in right ventricular free wall. Cardiac lesions increased in frequency and severity basally in left ventricular free wall, ventricular septum, and atria, but not in right ventricular free wall. Nephropathy lesions were selective for inner cortex and constitute a common and important side effect of chronic ADR intoxication in rabbits. Other lesions observed at necropsy were hepatic necrosis, skeletal muscle degeneration, osteodystrophy-associated fractures, peripancreatic fat necrosis, and testicular degeneration and atrophy.

Alopecia↗
PubMed1979

Infection of glutaraldehyde-preserved porcine valve heterografts.

Gross, histologic and ultrastructural changes associated with bacterial infection are described in four porcine valve heterografts that had been in place in patients for 6 days to 28 months. In one patient, culture of the aortic tissue tag included in the heterograft container grew Mycobacterium chelonei; however, examination of the heterograft, recovered at necropsy 6 days after implantation, revealed small colonies of bacteria that differed morphologically from mycobacteria. A second heterograft was the site of staphylococcal infection associated with extensive destruction of collagen in the leaflets. Similar destruction was observed in a third heterograft, which was found to have organisms on ultrastructural study even though bacterial cultures of the valve were negative. The fourth heterograft, from a patient who died of coronary embolism secondary to dislodgment of vegetative material, contained structures resembling lysed bacteria. Observations in these 4 patients and review of published reports of infection involving 43 other patients with porcine valve heterografts indicates that infection in these valves: (1) develops in the fibrin layer that covers the cusps, (2) can involve the collagen in the leaflets, and (3) is uncommonly (three patients) associated with valve ring abscesses.

Adult↗
PubMed1979

Anchoring fibrils in the normal canine respiratory system.

Electron microscopic study of the normal canine respiratory tree disclosed the presence of anchoring fibrils, a distinct class of fibrils of extracellular connective tissue, in association with the following types of cells: (1) basal cells and special type cells of trachea and bronchi; (2) ciliated cells and basal cells of bronchioles; (3) ductal cells, secretory cells, and myoepithelial cells of tracheobronchial glands. Anchoring fibrils in the normal respiratory system measured up to 6,000 A in length and from 170 to 400 A in thickness, and had a banding pattern that differed from that of collagen fibrils and connective tissue microfibrils. They formed arcs, the ends of which inserted into the basal lamina underlying the basal portions of the cells, often in the vicinity of hemidesmosomes. Anchoring fibrils decreased in number and size in the more distal portions of the respiratory tree, and were not found in alveolar septums. Anchoring fibrils in lung appeared similar to those described in other organs, but were often small and inconspicuous. The function of these structures is to reinforce the attachment of the epithelial basal lamina to the underlying connective tissues.

Animals↗
PubMed1979

Acute hypersensitivity pneumonitis: serial changes in lung lymphocyte subopulations after exposure to antigen.

The earliest lesion in hypersensitivity penumonitis is an acute inflammatory alveolitis characterized by parenchymal hemorrhage and accumulations of polymorphonuclear leukocytes within the lung. In many instances, this initial lesion is replaced by a more chronic alveolitis, with development of mononuclear cell interstitial infiltrate, granuloma formation, and interstitial fibrosis. To help define the mechanisms by which the early polymorphonuclear leukocyte alveolitis of acute hypersensitivity pneumonitis evolves into a chronic mononuclear-cell process, an animal model of the disease was developed using guinea pigs sensitized by footpad injeection with either ovalbumin (OVA) in complete Freund's adjuvant (CFA), CFA alone, or phosphate-buffered saline. Ten days after sensitization, the animals were challenged by intratracheal injection of either particulate OVA, particulate human serum albumin, or phosphate-buffered saline alone, and their lungs were evaluated sequentially for changes in histologic appearance and lymphocyte subpopulations. After challenge, only animals sensitized with CFA plus OVA and challenged with particulate OVA developed pulmonary lesions consistent with acute hypersensitivity pneumonitis. Within 4 h after challenge, these animals developed an acute hemorrhagic alveolitis that persisted for more than 24 h. By 48 to 96 h, the alveolitis evolved into a predominantly mononuclear-cell infiltrate. This change in the histologic appearance of the lungs in these animals was preceded by a rapid increase in the proportions of T-lymphocytes within the lungs, noted by 24 h after intratracheal challenge with specific antigen. Before intratracheal challenge with antigen, lung lymphocytes from only the group of animals immunized with CFA plus OVA were capable of proliferating on exposure to OVA in vitro. In the same group, lymphocytes recovered from the lung after intratracheal particulate OVA demonstrated blast transformation in vivo, a phenomenon not found in any other group. These studies suggest that the alveolitis of acute hypersensitivity pneumonitis is rapidly associated with changes in populations of immune effector cells before development of the mononuclear cell alveolitis characteristic of the chronic disease.

Alveolitis, Extrinsic Allergic↗
PubMed1979

Nuclear inclusions in alveolar epithelium of patients with fibrotic lung disorders.

Ultrastructural study of pulmonary biopsy specimens from patients with fibrotic lung disease disclosed the presence of nuclear inclusions in 1% or less of cuboidal alveolar epithelial cells in 9 of 19 patients, including 6 of 12 patients with idiopathic pulmonary fibrosis, 2 of 3 patients with collagen-vascular disease, and 1 of 3 patients with sarcoidosis. Nuclear inclusions were not observed by ultrastructural study in 5 control patients. The inclusions consisted of masses or aggregates of tubules which probably were derived from the inner nuclear membranes. These tubules were smooth-walled, showed branchings and bifurcations, were composed of single trilaminar membranes, usually had a clear content, and ranged from 500 to 1000 A in diameter. They resembled nuclear tubules which occur in other cell types under conditions of rapid growth or specific hormonal stimulation. Statistically significant differences between the groups of patients with and without nuclear inclusions in cuboidal alveolar epithelial cells were not found with respect to smoking history, degree of fibrosis in the lung biopsy specimen, or the degree of pulmonary physiologic impairment. However, the average age of the patients having nuclear inclusions was significantly greater than that of patients not having nuclear inclusions. In addition, the frequency of indentations in the nuclei of cuboidal alveolar epithelial cells was greater in patients with nuclear inclusions than in patients without nuclear inclusions. Highly significant correlations were observed between the presence of nuclear inclusions and the presence of a) anchoring fibrils and hemidesmosomes along the basal surfaces of alveolar epithelial cells and b) multilayering of the alveolar epithelium.

Aging↗
PubMed1979

Ultrastructure of pulmonary mast cells in patients with fibrotic lung disorders.

The topographic distribution, population density, and ultrastructural features of metachromatic cells (mast cells and basophilic leukocytes) were studied in lung biopsies from five control patients and 17 patients with fibrotic lung disorders. The great majority of metachromatic cells were mast cells. The average number of metachromatic cells per square millimeter of tissue section was much larger in patients with fibrotic lung disorders (45.8 +/- 6.5) than in control patients (2.6 +/- 1.6). In control patients, mast cells were most frequently seen in subpleural and perivascular connective tissue. In contrast, the vast majority of mast cells in patients with fibrotic lung disorders was present in thickened, fibrous alveolar septa; mast cells also were found within the alveolar epithelial layer and alveolar lumina. The quantitative distribution of different types of mast cell granules differed in the two groups of patients: granules composed of scrolls were more frequent in control patients, and granules of the combined type (containing mixtures of different components within the same granule) were more frequent in patients with fibrotic lung disorders. Mast cells in the latter patients appeared to migrate through defects in the basement membrane into the epithelial layer and alveolar lumina; mast cells in these areas often showed reduced numbers of granules and disorganized granule content. These changes suggest that pulmonary parenchymal mast cells in fibrotic lung disorders undergo a chronic process of partial degranulation which differs from that found in anaphylaxis; this chronic release of mast cell products may contribute to the continuing alveolar injury and the ventilation-perfusion inequalities observed in the fibrotic lung disorders.

Adult↗
PubMed1979

Inflammatory and immune processes in the human lung in health and disease: evaluation by bronchoalveolar lavage.

Bronchoalveolar lavage is an invaluable means of accurately evaluating the inflammatory and immune processes of the human lung. Although lavage recovers only those cells and proteins present on the epithelial surface of the lower respiratory tract, comparison with open lung biopsies shows that these constituents are representative of the inflammatory and immune systems of the alveolar structures. With the use of these techniques, sufficient materials are obtained from normal individuals to allow characterization of not only the types of cells and proteins present but their functions as well. Such observations have been useful in defining the inflammatory and immune capabilities of the normal lung and provide a basis for the study of lung disease. Lavage methods have been used to characterize inflammatory and immune processes of the lower respiratory tract in destructive, infectious, neoplastic, and interstitial disorders. From the data already acquired, it is apparent that bronchoalveolar lavage will yield major insights into the pathogenesis, staging, and therapy decisions involved in these disorders. (Am J Pathol 97:149--206, 1979).

Bacterial Infections↗
PubMed1979

Pathologic features of adriamycin toxicosis in young pigs: nonskeletal lesions.

In ten experiments, 53 castrated male 4- to 8-week-old weanling pigs were given adriamycin (ADR) IV at mean dosages of 0.64, 1.0, 1.6, 3.2, or 6.4 mg/kg/week at various frequencies for up to 20 weeks. Mortalities in pigs given these dosages were 0% after 112 days, 100% after 134 days (survival time was 48 to 134 days), 91% after 75 days (survival time was 5 to 75 days), 100% after 28 days (survival time was 23 to 28 days), and 100% after 14 days (survival time was 10 to 14 days), respectively. Survival time was prolonged in younger pigs and in pigs given smaller but more frequent dosages of ADR. Characteristic gross and histopathologic alterations of ADR toxicosis were observed in pigs given 1.0, 1.6, 3.2, or 6.4 mg/kg/week mean dosages. The most frequent lesions were in the alimentary tract, myeloid and lymphoid tissues, skin, and perivascular tissues at injection sites. Alimentary tract lesions were mucosal epithelial atrophy, with secondary fibrinonecrotic inflammation in the oral cavity and large intestine. Marked hypoplasia was seen in bone marrow and lymphoid tissues, with frequent terminal hemorrhagic diathesis and septicemia. Several days before death, the pigs developed severe dermatitis over the ventral portion of the abdomen and inner surfaces of the limbs. Perivascular necrosis and cellulitis produced by extravasation of ADR was a frequent complication of treatment. Terminal severe acute pneumonia occurred in most pigs. Pericarditis or cardiomyopathy (or both) developed in 14 pigs, given 0.64, 1.0, or 1.6 mg/kg each week (mean cumulative dosage 520.5 mg/m2 of body surface). Characteristic histopathologic and ultrastructural alterations in affected cardiac muscle cells were vacuolar degeneration, myocytolysis, and hyaline necrosis. Nephrotoxicosis also was in pigs with chronic ADR toxicosis. Systemic antibiotic treatment did not prolong survival of ADR-treated pigs in two experiments, but did in one other experiment.

Animals↗