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Biomedical subjects

V J Ferrans

Publications and source records attributed to V J Ferrans.

At least 253 records · Page 14Linked to original sources
PubMed1984

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% +/- 1.14% of all cells in BAL fluid). Immunoelectron microscopic studies revealed that the cells labeled in these patients (n = 13) contained Langerhans granules. The number of fluorescent cells in the other 113 patients was significantly smaller (mean +/- SEM, 0.20% +/- 0.04% of all cells; P less than 0.001). In the 3 control patients, in the 43 patients with sarcoidosis, and in 61 of the 67 patients with miscellaneous disorders unrelated to histiocytosis X, no cells or less than 1% of the total were labeled; however, in the 6 remaining patients in this miscellaneous group, 1.3 to 2.8% of all cells in BAL were labeled. In 3 of these 6 patients, immunoelectronmicroscopic examination showed that the cells labeled by OKT6 had the general characteristics of Langerhans cells but lacked Langerhans granules. OKT3, OKT4, and OKT8 monoclonal antibodies did not stain histiocytosis X cells in BAL fluid.

Antibodies, Monoclonal↗
PubMed1984

Ultrastructural alterations in the atrial myocardium of pigs with acute monensin toxicosis.

Monensin, A Na+-selective carboxylic ionophore, produces left atrial damage in pigs given toxic doses. Eight weanling pigs were given mycelial monensin orally (40 mg/kg body weight) and were killed on days 1, 2, 4, and 16 (two animals at each time interval) for ultrastructural study of the left atrial lesions. On days 1-4, extensive necrosis with contraction bands was present. Rapid macrophagic invasion and phagocytosis of sarcoplasmic debris was seen on days 2 and 4. Missing necrotic myocytes were outlined by persistent "tubes" of external laminas. In some surviving myocytes, sublethal injury was evident on day 1 by mitochondria with condensed conformation and on days 2, 4, and 16 by moderate to marked myofibrillar lysis and sarcoplasmic vacuolation. Monensin cardiotoxicity in pigs constitutes a unique example of selective injury to atrial myocardium.

Acute Disease↗
PubMed1984

Ultrastructural alterations in skeletal muscle of pigs with acute monensin myotoxicosis.

Large doses of monensin, a Na+-selective carboxylic ionophore, produce polyfocal, monophasic necrosis of skeletal muscle, with Type I fiber selectivity, in swine. For a study of the sequential ultrastructural alterations in affected skeletal muscles, 14 weanling pigs were given 40 mg monensin/kg body weight and were euthanatized 1, 2, 4, 8, and 16 days later. Myotoxicosis and myoglobinuria were apparent clinically. At necropsy, white, dry areas of necrosis were present in the muscle masses of the anterior and posterior thigh, shoulder, and loin. Two patterns of skeletal muscle necrosis were observed on Day 1, especially in Type I fibers. In fibers exhibiting the first of these patterns, the contractile material was disrupted, forming dense amorphous and filamentous clumps scattered within the persistent sheaths of external lamina (sarcolemmal tubes); the mitochondria were swollen and contained flocculent matrix densities, and the nuclei were pyknotic. Fibers showing the second pattern were uniformly dense, but their sarcoplasm was not disrupted. Sublethally injured fibers were also observed and showed focal myofibrillar lysis. On Days 2 and 4, the necrotic muscle had marked infiltration of macrophages in the interstitium and within sarcolemmal tubes. Rapid resolution of the fiber necrosis occurred by phagocytosis of the sarcoplasmic debris. Regeneration of affected muscles developed early following injury and progressed rapidly to complete restoration of the necrotic muscles without residual fibrosis. Regeneration was initiated on Day 1 by activation of satellite cells to form presumptive myoblasts; on Days 4 and 8 these cells showed evidence of fusion, forming myotubes to restore the necrotic fibers.

Acute Disease↗
PubMed1983

Formation of cartilage in bioprosthetic cardiac valves implanted in sheep: a morphologic study.

Foci of cartilage were found in 12 of 120 bioprostheses implanted in young sheep for 13 to 24 weeks, but in none of 47 bioprostheses implanted for less than 13 weeks. Cartilage was found more frequently (p less than 0.01) in bioprotheses implanted in the tricuspid position than in those implanted in the mitral position. In porcine aortic valvular bioprostheses, the cartilage was preferentially localized in the region of the muscle shelf; in pericardial bioprostheses, it occurred in the fibrous sheaths covering the cusps. In both instances, the cartilage was found to undergo calcification and was considered to be formed by metaplasia of connective tissue cells of host origin.

Animals↗
PubMed1983

The development of alveolar septa in fetal sheep lung. An ultrastructural and immunohistochemical study.

The morphogenesis of pulmonary alveolar septa in the sheep was studied by light microscopy, transmission electron microscopy and light microscopic immunohistochemistry for the detection of elastin. The primordia of alveolar septa developed in the glandular stage in areas subjacent to the epithelium, and formed alveolar septa by protruding into the glandular lumina. In their earliest stage, the primordia consisted of groups of fibroblasts, which were associated with elastic fibers and unit collagen fibrils and were surrounded by epithelial basement membrane and by more immature fibroblasts. The fibroblasts in the primordia subsequently became myofibroblasts or smooth muscle cells. In the alveolar zone of the glands, elastic fibers were exclusively found in the primordia of alveolar septa in early developing lung. In early developing lung, wavy, thickened epithelial basement membranes were found in the regions of the glands, which eventually underwent considerable expansion of their surface areas, especially in the primordia of alveolar septa and the bifurcations in the alveolar zones. Areas of fusion of the basement membranes of capillary endothelial cells and epithelial cells in the alveolar zone were found after the formation of the primordia of alveolar septa was accomplished. These areas of fusion were not found in the primordia themselves, but in regions between the primordia. Epithelial cell flattening and differentiation occurred after the formation of the primordia of alveolar septa, and flattening was first observed in the areas of the primordia and the bifurcations of the alveolar zones.

Animals↗
PubMed1983

Early degradation of collagen after acute myocardial infarction in the rat.

After acute myocardial infarction (MI), proteolysis of necrotic myocardium is mediated by infiltrating inflammatory cells at the infarct margins. Collagen forms a structural fibroskeleton in healthy myocardium, and after MI this collagen may continue to provide significant tensile strength to the necrotic muscle wall. To determine whether collagen is also degraded (which might decrease infarct wall strength) and, if so, whether inflammatory cell proteases are implicated, hydroxyproline was measured from infarct zone and normal zone tissue from 24-hour infarcts produced in control rats and in rats made leukopenic (white blood cell count less than 300/mm3) by prior whole-body irradiation. Hydroxyproline was measured after precipitation of tissue homogenates with trichloroacetic acid to separate partially degraded collagen from larger collagen molecules that might retain structural importance. At 24 hours, there was significant (25%) collagen degradation in the infarct zone (p less than 0.01) in control rats but not in leukopenic rats. Tissue cell counts revealed a paucity of inflammatory cells in the infarct margins in leukopenic rats. Electron microscopic studies revealed greater preservation of collagen in the 24-hour-old infarcts of irradiated leukopenic rats compared with those of control rats. These results suggest that at 24 hours after experimental MI in the rat, there is significant collagen degradation mediated by inflammatory cell proteases.

Animals↗
PubMed1983

Clinical and morphologic cardiac findings after anthracycline chemotherapy. Analysis of 64 patients studied at necropsy.

The relation between clinical evidence of and histologic signs of anthracycline cardiotoxicity was evaluated by reviewing the clinical and morphologic findings in 64 patients studied at necropsy, all of whom had received doxorubicin or daunorubicin chemotherapy during life. Of the 64 patients, 20 (31%) had documented clinical toxicity consisting of impaired left ventricular systolic performance; in 7 (35%) of these 20 patients, histologic signs of toxicity were absent. In the remaining 13 patients with clinical toxicity, histologic signs of toxicity ranged from mild to severe. Of the 44 (69%) patients without clinical signs of drug toxicity, 21 (48%) had no histologic sign of cardiotoxicity; in 23 (52%) of the patients without clinical toxicity, however, morphologic signs of cardiotoxicity were nevertheless present--mild in most patients, but extensive in 4. Signs of extensive histologic toxicity (19 [30%] of 64 patients) were associated with large doses (greater than 450 mg/m2) of the drug, mediastinal irradiation, and age greater than 70 years. This study suggests that attempts to monitor cardiotoxicity by serial evaluation of cardiac histology in patients undergoing anthracycline chemotherapy may be seriously limited by the fact that clinical evidence of toxicity may be present without histologic signs of toxicity; likewise, histologic signs of anthracycline toxicity may be present without clinical evidence of toxicity.

Adolescent↗
PubMed1983

Changes in DNA content, number of nuclei and cellular dimensions of young rat atrial myocytes in response to left coronary artery ligation.

Studies of enzymatically isolated myocytes from atria of young male Sprague-Dawley rats at 11 days after left coronary artery ligation show that a major response of atrial myocytes to ventricular infarction is binucleation. In sham-operated animals, 23.2% of left and 15.5% of right atrial myocytes were binucleated, compared to 77.8% of left and 40.5% of right atrial myocytes of infarcted animals. Examination of 150 g and 250 g unoperated control animals indicate that this response is occurring at a time when a small but significant amount of binucleation is also occurring as a normal part of growth. Using a Feulgen-acriflavine-SO2 method for cytofluorometry, a significant increase in ploidy was seen in left atrial myocytes of infarcted animals over those of sham or control animals. The number of left atrial myocytes in infarcted animals having a ploidy level above 3C was 10.8% above sham values. The mean length of binucleated myocytes of left atrium was significantly greater in infarcted animals (119.8 microns) than in sham-operated animals (97 microns) and the mean length of mononucleated myocytes was greater in infarcted animals (104.1 microns) than in sham-operated animals (77 microns). Thus, cardiac myocytes are capable of a substantial response to a stressful situation by increases in cell length, number of nuclei and ploidy. Study of a model system such as the rat atrium may yield an understanding of the mechanisms involved in the induction of these nuclear changes.

Animals↗
PubMed1983

Examination of the protective effect of ICRF-187 and dimethyl sulfoxide against acetaminophen-induced hepatotoxicity in Syrian golden hamsters.

The protective activity of 1,2-bis(3,5-dioxopiperazin-l-yl)propane (ICRF-187) and dimethyl sulfoxide (DMSO) was tested against acetaminophen-induced hepatotoxicity. Male Syrian golden hamsters injected intraperitoneally between 18:00 h and 20:00 h for 2 consecutive days with acetaminophen (N-acetyl-p-aminophenol) (300 mg/kg) displayed signs of hepatotoxicity as evidenced by increases in enzyme activity and cellular damage. Forty-eight hours after the second acetaminophen dose, the activities of serum glutamic-pyruvic transaminase and alkaline phosphatase were increased compared with levels found in hamsters given only saline. In addition, hepatocellular necrosis was evident in acetaminophen-treated animals. ICRF-187 (300 mg/kg) given 1 h before acetaminophen attenuated the increases in enzyme activities, and both DMSO (7.3 g/kg) and ICRF-187 reduced the incidence and severity of acetaminophen-induced hepatocellular injury. Both ICRF-187 and DMSO are capable of altering free radical-mediated toxicity in other experimental systems. Whether these compounds reduce acetaminophen-induced liver toxicity by a similar mechanism remains to be determined.

Acetaminophen↗
PubMed1983

Morphology of the heart in hypertrophy.

Cardiac hypertrophy involves not only an increase in heart size but progressive, initially subtle, structural changes in muscle cells. The ability to describe these changes in detail has contributed greatly to our understanding of their possible functional significance. Structural and functional correlations in the evolving progression of cardiac hypertrophy are examined.

Cardiomegaly↗
PubMed1983

Specificity of light and electron microscopic features of hypertrophic obstructive and nonobstructive cardiomyopathy. Qualitative, quantitative and etiologic aspects.

A review is presented of the histologic and ultrastructural abnormalities found in the hearts of patients with hypertrophic cardiomyopathy. Evidence is presented to show that myocardial fiber disarray is found in hypertrophic cardiomyopathy as well as in other conditions; however, in the latter it seldom involves more than 5% of the myocytes in transverse sections of ventricular septum. A new theory of morphogenesis is proposed to account for the asymmetric cardiac hypertrophy that characterizes hypertrophic cardiomyopathy. This theory is summarized as follows: (1) hypercontractility is the underlying abnormality affecting cardiac myocytes; (2) this hypercontractility is present during embryonic development and constitutes the stimulus to the inappropriate increase in cardiac mass that takes place in hypertrophic cardiomyopathy; (3) during embryonic development this stimulus results in increased mitotic division (i.e. hyperplasia) rather than in increased size of individual myocytes (i.e. hypertrophy); (4) hyperplasia is preferentially increased in the ventricular septum (perhaps because of the mechanical forces exerted by left and right ventricular contraction on the ventricular septum), thus exaggerating the asymmetric growth that occurs normally in this area during prenatal development; (5) after birth, the septal asymmetry does not regress in patients with hypertrophic cardiomyopathy, as it does in normal individuals, because it is complicated by hyperplasia (i.e. increased numbers of myocytes are already present in the ventricular septum); (6) the prenatal phase of hyperplasia is followed by a postnatal phase of gradual, progressive hypertrophy in which myocytes enlarge, septal hypertrophy becomes exaggerated, and clinical symptoms eventually develop.

Cardiomyopathy, Hypertrophic↗
PubMed1983

Cholesteryl ester crystals in a porcine aortic valvular bioprosthesis implanted for eight years.

Masses of crystals, which were largely composed of cholesteryl esters, were found in a porcine aortic valvular bioprosthesis removed eight years after implantation in the mitral position in a patient with rheumatic mitral valvular stenosis. Histologic sections of grossly raised and nonraised yellow lesions in the three cusps of this bioprosthesis revealed large clefts, which on frozen section contained lipid-positive, birefringent crystals. These crystals gave a positive reaction with the Schultz test for cholesterol. Biochemical analyses of isolated nodules revealed a cholesterol content of 40 nmole/mg of wet tissue. Of this cholesterol, 88 percent was esterified, and the remaining 12 percent was free cholesterol. These cholesterol deposits are most likely derived from blood lipids; however, they were not related to hyperlipidemia, since the patient had normal blood levels of cholesterol and triglycerides.

Aged↗
PubMed1983

Cardiac ultrastructure in primary restrictive cardiomyopathy.

A five-year clinical follow-up and the results of myocardial biopsies are described in a patient with primary restrictive cardiomyopathy. Histologic examination of a right ventricular endomyocardial biopsy taken early in the course of the illness was not contributory. Histologic examination of a left ventricular endomyocardial biopsy five years later showed hypertrophy and disarray of myocytes, thickening of the endocardium, and interstitial fibrosis. Connective tissue was compact and regularly oriented in the endocardium, but tangled and irregularly oriented in the interstitium. It is concluded that the irregular network of collagen fibrils and elastic fibers limits diastolic relaxation and prevents ventricular dilatation; that the coexisting hypertrophy results from an attempt to maintain normal pump function; and that the myocyte disarray is a consequence of abnormal mechanical forces generated under conditions of severe fibrosis.

Biopsy↗
PubMed1983

Influence of vitamin E and ICRF-187 on chronic doxorubicin cardiotoxicity in miniature swine.

Studies were made of the potential of vitamin E and ICRF-187 to protect against the cardiotoxicity resulting from chronic administration of doxorubicin. Miniature swine (19 to 40 kg) received six injections of doxorubicin (1.6 mg/kg) at 3-week intervals (total dose, 9.6 mg/kg), either alone or concurrently with vitamin E (5000 IU/day for 4 days and 1000 units/day for the next 17 days). In a second study, miniature swine received six injections of doxorubicin (2.4 mg/kg) at 3-week intervals (total dose 14.4 mg/kg), either alone or 30 minutes after 12.5 mg of ICRF-187/kg (intraperitoneally). All animals were sacrificed 3 weeks after the last injection. The frequency and extent of myocardial lesions (vacuolization and myofibrillar loss) were scored on a scale of 0 to 4+. Such lesions were noted in eight of nine pigs given 9.6 mg/kg of doxorubicin alone and in all pigs receiving doxorubicin and vitamin E; however, the severity of the lesions was decreased in the latter animals (average score 1.0, compared with 1.8 in those receiving doxorubicin alone). All swine receiving 14.4 mg/kg of doxorubicin alone developed myocardial lesions (average score, 2.7); these lesions were severe (3+) in four of the animals. In contrast, cardiac lesions were absent in two and minimal (average score, 0.7) in five of the seven animals given 14.4 mg/kg of doxorubicin in combination with ICRF-187.

Animals↗