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V J Ferrans

Publications and source records attributed to V J Ferrans.

At least 127 records · Page 7Linked to original sources
PubMed1993

Antibodies to laminin and immunohistochemical localization of laminin in chronic chagasic cardiomyopathy: a review.

Antibodies against laminin were determined by ELISA in forty six patients suffering from Chagas' disease and twenty healthy persons (control group). The patients were divided into three groups according to the severity of clinical, electrocardiographic and echocardiographic studies. Histologic, ultrastructural and immunohistochemical studies were made of endomyocardial biopsy specimens from 10 of these patients with chronic Chagasic cardiomyopathy. Antibodies to laminin were detected in 50% of the patients in each of the three groups. However analysis of the data did not allow us to determine any significant correlation among the severity of the different clinical and non-invasive studies and the level of circulating antibodies to laminin. The highest titers of antilaminin antibodies were detected in the group with severe cardiological alterations (37% of the patients). Histological and electron microscopic observation of myocardial biopsies disclosed marked thickening of the basement membranes of the myocytes, endothelial cells and vascular smooth muscle cells. Light (peroxidase-labeled antibodies) and electron (gold-conjugated antibody) microscopic immunohistochemical methods revealed a positive reaction for laminin in these thickened basement membranes. This thickening may develop as a consequence of: a) an immunologic reaction which is triggered by the presence of a laminin-like molecule on the surfaces of T. cruzi amastigotes and trypomastigotes; b) an immunologic response to direct injury of basement membranes causing some of their components to become antigenic; c) myocardial fibrosis, with synthesis of new connective tissue components, and d) a combination of the preceding factors. The relationship of these changes to antilaminin antibodies remains unclear.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Localization of basic fibroblast growth factor in bovine endothelial cells: immunohistochemical and biochemical studies.

To gain insight into the mechanisms of synthesis, storage, and release of basic fibroblast growth factor (bFGF), we studied the immunohistochemical localization of bFGF in bovine coronary artery, coronary sinus, and adrenal capillary endothelial cells grown in culture. Light and electron microscopic immunohistochemical studies were performed using the ABC immunoperoxidase method on p-formaldehyde-fixed cells. Five different anti-bFGF antibodies gave similar results in all cell types. In subconfluent cells, immunoreactivity was noted in the nuclear chromatin, nucleoli, cytosol, cytoplasmic vesicles (some of which appeared to fuse with the plasma membrane), and extracellular matrix. No reaction was found in endoplasmic reticulum or Golgi zones. Confluent cells demonstrated less immunoreactivity in the nuclei and cytosol but more in the extracellular matrix. Some cells of senescent morphology showed only cytoplasmic staining; however, no cells were found with only nuclear staining. Biochemical studies showed that three forms of bFGF (18, 24, and 26 kDa) were present in endothelial cells and varied with different culture conditions. Protection analysis indicated that bFGF mRNA is less abundant in postconfluent cells than in subconfluent cells. These data suggest that subconfluent cells synthesize bFGF and transport it into the nucleus and exocytotic vesicles, while confluent cells synthesize little bFGF but store it in extracellular matrix, cytoplasmic vesicles, and nuclei.

Animals↗
PubMed1993

Timing of treatment with ICRF-187 and its effect on chronic doxorubicin cardiotoxicity.

Studies were conducted to evaluate whether the timing of administration of ICRF-187 [(+)-1,2-bis(3,5 dioxopiperazinyl-1-yl)propane] would influence the degree of cardioprotection provided by this agent against the development of doxorubicin-induced chronic cardiomyopathy. Beagle dogs (8.5-14 kg) received either doxorubicin alone (1.75 mg/kg, i.v., n = 8), doxorubicin (1.75 mg/kg) simultaneously with ICRF-187 (35 mg/kg, i.v., n = 8), or doxorubicin (1.75 mg/kg) followed 2 h later by ICRF-187 (35 mg/kg, n = 8). Control animals received ICRF-187 (35 mg/kg, n = 4) or saline (n = 4). All animals received a course of seven treatments, each given 3 weeks apart, and were killed 3 weeks after the last treatment. Semiquantitative grading of histologic sections of myocardium showed that as compared with animals treated with doxorubicin alone, the incidence and the severity of the doxorubicin-induced myocardial lesions were reduced in the two groups of animals given doxorubicin plus ICRF-187. However, protection was significantly better in dogs receiving ICRF-187 and doxorubicin simultaneously than in those given ICRF-187 2 h after doxorubicin. These observations were interpreted as indicating that the timing of administration of ICRF-187 with respect to that of doxorubicin is an important factor in determining the degree of cardioprotection and that there is a "time window" in which ICRF-187 exerts optimal effects.

Animals↗
PubMed1993

Immunohistochemical localization of laminin in the hearts of patients with chronic chagasic cardiomyopathy: relationship to thickening of basement membranes.

Histologic, ultrastructural, and immunohistochemical studies were made of endomyocardial biopsy specimens from 10 patients with chronic chagasic cardiomyopathy. Histologic and electron microscopic observation disclosed marked thickening of the basement membranes of the myocytes, endothelial cells, and vascular smooth muscle cells in all patients. Light (peroxidase-labeled antibodies) and electron (gold-conjugated antibody) microscopic immunohistochemical methods revealed a positive reaction for laminin in these thickened basement membranes. This thickening of basement membranes may develop as a consequence of: (1) an immunologic reaction that is triggered by the presence of a laminin-like molecule on the surfaces of Trypanosoma cruzi amastigotes and trypomastigotes; (2) an immunologic response to direct injury of basement membranes causing some of their components to become antigenic; (3) myocardial fibrosis, with synthesis of new connective tissue components; and (4) a combination of the preceding factors. The relationship of these changes to antilaminin antibodies requires clarification.

Adult↗
PubMed1993

Human cryopreserved homografts: electron microscopic analysis of cellular injury.

Twenty-five human cryopreserved valves with harvest-related warm ischemic times (WITs) ranging from 0 to 20 hours were studied using transmission electron microscopy to characterize the effects of harvesting and preservation on leaflet matrix cells. The valves were divided into seven groups on the basis of WIT and processed using standard transmission electron microscopic methods. Each cell (528 micrographs) was graded for reversible and irreversible cellular injury and subjected to a Cochran-Mantel-Haenszel trend analysis. Our results demonstrated a progression in cellular injury with increasing WIT. During the first 12 hours of warm ischemia, reversible cellular injury predominated (0.0%, 30.0%, 51.2%, 31.3%, 35.1%, 45.1%, and 40.0% at WITs of 0, 1, 2, 8, 12, 16, and 20 hours, respectively). A positive correlation (p < 0.0001) between increasing WIT and reversible cellular injury through the first 12 hours was observed. Minimal morphologic evidence of irreversible injury was noted in valves harvested with less than 12 hours of warm ischemia; however, after 12 hours there was a marked increase (0.0%, 0.0%, 4.7%, 2.4%, 2.7%, 31.4%, and 40.0% at WITs of 0, 1, 2, 8, 12, 16, and 20 hours, respectively) in irreversible cellular injury (p < 0.001 between 12 and 20 hours WIT). These data demonstrate a progression in cellular injury with increasing WIT. There was virtually no morphologic injury in valves with harvest-related WITs less than 2 hours and minimal irreversible cellular injury observed in valves exposed to 12 hours or less of warm ischemia. If cellular viability is critical to homograft durability then harvest-related warm ischemia may need to be restricted to 12 hours.

Aortic Valve↗
PubMed1993

Pulmonary Langerhans cell granulomatosis (histiocytosis X). A clinicopathologic study of 48 cases.

We report the clinical and histologic findings of lung biopsies from 48 patients with pulmonary Langerhans cell granulomatosis (PLCG) and show how special techniques such as immunohistochemistry, electron microscopy (EM), and high resolution computerized tomography (HRCT) of the lungs can be useful in diagnostically challenging cases. Nineteen patients were men and 29 were women. The median age was 33 years (range 15-54 years). Two had pituitary involvement. Bone lesions were observed in four patients and biopsy proven in two. All patients were cigarette smokers. In six patients HRCT revealed a combination of thin-walled cystic and nodular lesions. The pathologic diagnosis was established on the basis of open lung biopsy specimens in 44 cases and transbronchial biopsy specimens in 4 of 10 cases. In two transbronchial biopsies, diagnostic PLCG infiltrates were seen in toluidine blue-stained thick sections in the tissue processed for EM but not on the tissue processed for histology. EM in both of these cases revealed Birbeck granules within LCs. The diagnosis was supported by a positive bone biopsy in one of these patients and characteristic HRCT findings in the other. The antibody to S100 protein stained the LC infiltrates in the five cases studied. This staining and the characteristic findings on HRCT confirmed the diagnosis in one case in which the PLCG lesions were obscured by atelectasis. The frequent finding of intraluminal fibrosis (78% of open lung biopsies) supports the recent suggestion that this alteration plays an important role in the pathogenesis of fibrotic remodeling in PLCG. The strong association of PLCG with cigarette smoking and the frequent peribronchiolar location of PLCG lesions (87% of open lung biopsies) in our cases are consistent with the concept that in adults this disorder is associated with an abnormal response to cigarette smoke.

Adolescent↗
PubMed1993

Interstitial dendritic cells of the rat heart. Quantitative and ultrastructural changes in experimental myocardial infarction.

BACKGROUND: This study was undertaken to investigate the qualitative and quantitative changes that interstitial dendritic cells (IDC) of the heart undergo during the time course of experimental myocardial infarction. METHODS AND RESULTS: Left coronary arterial ligations were performed in 43 rats that were killed 2, 4, 7, 14, and 21 days after surgery. Thirteen unoperated and 39 sham-operated rats were used as controls. Frozen sections were stained with monoclonal antibodies (OX 6 and W3/25) to identify and count IDC by light microscopy. Immunoelectron microscopy was also used to identify IDC. The number of IDC per mm2 of tissue section was calculated for all hearts. In hearts with myocardial infarction, IDC were counted in three areas: the center of the myocardial infarction, the border zone, and the noninfarcted left ventricle. In OX 6 antibody-stained preparations, the number of IDC per mm2 was 82 +/- 10 in the left ventricle of unoperated rats. Hearts with myocardial infarction showed marked increases in the numbers of IDC per mm2 in the border zone (796 +/- 79 at 7 days and 528 +/- 98 at 14 days). In the border zone, IDC often were associated with small clusters of T-helper lymphocytes, which reacted with W3/25 antibody (the rat homologue of human CD4). The center of the myocardial infarction showed an increase in IDC only on day 7 (120 +/- 18). By 21 days, IDC in the border zone were only slightly increased (159 +/- 15). CONCLUSIONS: These findings suggest that IDC migrate to the myocardial infarction border zone. They participate in the activation of lymphocytes and in the initiation of immune responses and decrease in number as inflammation subsides and scarring develops.

Animals↗
PubMed1993

Cardiotoxicity of human recombinant interleukin-2 in rats. A morphological study.

BACKGROUND: One of the side effects of interleukin 2 (IL-2) cancer immunotherapy in humans is the vascular leak syndrome, which is frequently associated with depression of myocardial function, myocarditis, and myocardial necrosis. METHODS AND RESULTS: To investigate this cardiotoxicity, IL-2 (three doses of 5 x 10(5) Cetus units/day i.p.) was given to rats for 2, 3, or 5 days. Heart, lung, liver, spleen, and kidney tissues were studied by light and electron microscopy and with immunoperoxidase techniques. Cardiac changes consisted of focal lymphocytic and eosinophilic infiltration, myocyte vacuolization, myofibrillar loss, and necrosis. Ultrastructural alterations included swelling of endothelial cells, with dissociation of intercellular junctions, migration of lymphocytes into the interstitium, and interstitial hemorrhage and edema. Close contact between infiltrating lymphocytes, particularly large granular lymphocytes, and cardiac myocytes was often observed in areas of tissue damage. All lesions were more severe on day 5 than on days 2 and 3. Immunoperoxidase stains demonstrated asialo GM1 ganglioside antibody-positive, granular lymphocytes to be much more frequent in myocardium of IL-2-treated rats than in that of control rats. CONCLUSIONS: Although we cannot exclude the possibility of a direct toxic effect of IL-2 on myocytes, our observations suggest that the myocardial damage produced by this agent is triggered by IL-2-activated lymphocytes that exert cytolytic effects, first on endothelial cells and then on cardiac myocytes, thus producing lesions that involve both the cardiac microcirculation and the muscle cells.

Animals↗
PubMed1993

Differential sensitivity of rat cardiac sarcolemma and mitochondria to damage induced by lipid peroxidation.

It is well known that the sarcolemma is the organelle most susceptible to lipid peroxidative attack in the isolated membrane preparations. To determine whether this also occurs in the intact heart, we studied the effect of cumene hydroperoxide, an agent capable of initiating lipid peroxidation, on the ultrastructure and lanthanum (La) staining of isolated rat hearts perfused with HEPES buffer (pH 7.4) containing: 140 mM NaCl, 5 mM KCl, 1 mM MgCl2, 3 mM HEPES, 1.5 mM CaCl2 and 11 mM glucose. No ultrastructural alterations or intracellular deposits of La were observed in myocytes of rats perfused with HEPES buffer. Perfusion with cumene hydroperoxide (0.5 mM) for 30 min induced a release of malondialdehyde-like substance in the perfusate and a spectrum of myocardial ultrastructural alterations. La was always observed only outside the sarcolemma in myocytes with moderate damage consisting of clearing of the mitochondrial matrix and slight margination of chromatin in the nuclei. Intracellular La was found in myocytes with severe and irreversible damages consisting of fragmentation of cristae and electron-dense amorphous particles in mitochondria. La was deposited on the outer surface of the mitochondrial membranes, lipid droplets and myofilaments. These data suggest that mitochondria are more susceptible than is the sarcolemma to lipid peroxidation induced by cumene hydroperoxide in the beating rat heart.

Animals↗
PubMed1993

Dendritic cells in the hearts of spontaneously hypertensive rats treated with doxorubicin with or without ICRF-187.

Histological and immunohistochemical studies using specific monoclonal antibodies were made to evaluate the severity of the chronic cardiomyopathy and the quantitative changes in interstitial dendritic cells (antigen-presenting cells), T helper lymphocytes, T cytotoxic/suppressor lymphocytes, and macrophages in the hearts of spontaneously hypertensive rats (SHRs) treated with doxorubicin at 1 mg/kg per week for 3, 6, 9 or 12 weeks. In addition, an assessment was made of the modifications of the responses of these cell populations by pretreatment of the SHR with ICRF-187, which protects against doxorubicin cardiotoxicity. The number of interstitial dendritic cells/mm2 of section of left ventricle was similar in saline-treated control SHRs (76 +/- 6) and in those treated with ICRF-187 alone (75 +/- 2) but increased markedly (319 +/- 33) in animals receiving a total cumulative dose of 12 mg/kg doxorubicin. Treatment with ICRF-187 prior to each administration of doxorubicin attenuated in a dose-dependent manner the increase in numbers of dendritic cells induced by doxorubicin (231 +/- 47, 174 +/- 11, and 100 +/- 16 cells/mm2) after treatment with 6.25, 12.5, and 25 mg of ICRF-187, respectively. Doxorubicin also induced increases in the numbers of T helper lymphocytes and macrophages but not of T cytotoxic/suppressor lymphocytes. These increases were also attenuated by pretreatment with ICRF-187. These data were interpreted as indicating that doxorubicin cardiotoxicity results in the release of substances that initiate immune reactions involving the antigen-presenting cells of the heart and that such reactions are attenuated by pretreatment with ICRF-187.

Animals↗
PubMed1992

Effect of ICRF-187 on the pulmonary damage induced by hyperoxia in the rat.

Histological and ultrastructural studies were made of the lungs of rats that were exposed to 100% oxygen for 60 h and were treated with either normal saline or with ICRF-187, a bis-diketopiperazine derivative of EDTA that has the capacity to chelate iron. This metal is thought to be needed to catalyze the formation of toxic oxygen free radicals. ICRF-187 (20 mg/kg) was given intraperitoneally at approximately 12 h intervals (5 doses) during the 60 h exposure. Seven of the ten saline-treated rats exposed to oxygen died prior to the end of the study whereas only one of the 10 rats in the ICRF-187-treated group died. This difference in mortality is found to be statistically significant (P less than 0.05). All saline-treated rats showed light and electron microscopic evidence of pulmonary damage. ICRF-187 attenuated the morphologic alterations observed by light microscopy (intra-alveolar edema, inflammatory exudates and bronchiolar epithelial cell swelling and hyperplasia; P less than 0.05). In addition, electron microscopic evaluation revealed that capillary thrombi, endothelial cell alterations and alveolar epithelial cell damage also were less severe in ICRF-187-treated rats. It is concluded that ICRF-187 may provide a new and useful approach for the prevention of hyperoxia-induced pulmonary damage.

Animals↗
PubMed1992

Electron microscopic study of vascular regeneration in rat tracheal mucosa following physical curettage.

Transmission and scanning electron microscopic studies were made of regeneration of the vascular network of rat tracheal mucosa on 30 min to 8 hr after the mechanical curettage. The vascular network casts were made by infusion of Mercox resin through the aortic arch for scanning electron microscopy. At 30 min after curettage, vascular thromboses were observed, and terminal blind branches were formed in the injured blood vessels areas through SEM observation. Diapedesis of leukocytes appeared at 30 min after curettage from intact venules at the wound margins. Recovery from the loss of endothelial cells began at 30 min after curettage. At 3 hr after curettage, vascular indentation (protrusion) and vascular process (bud-like process) were developed from intact venules at the wound margins. It is concluded that the formation of thrombus and terminal blind branch vessels constitute the initial reparative reactions of the injured vascular network and that new vessels then begin to form by outgrowth of protrusions and bud-like processes from intact venules at the wound margins.

Animals↗
PubMed1992

The heart in Tangier disease. Severe coronary atherosclerosis with near absence of high-density lipoprotein cholesterol.

Cardiac necropsy findings are described in a 72-year-old man with Tangier disease whose plasma total cholesterol levels averaged 70 mg/dL, low-density lipoprotein cholesterol level was 45 mg/dL, and high-density lipoprotein cholesterol level was 1.4 mg/dL, and who had coronary artery bypass grafting for severe atherosclerotic coronary artery disease. At necropsy, 24 of the 72 (33%) 5-mm segments of the 4 major (right, left main, left anterior descending, and left circumflex) native coronary arteries and 4 of the 27 (15%) 5-mm segments of the saphenous vein aortocoronary bypass conduits were narrowed by more than 75% in cross-sectional area by atherosclerotic plaques. The plaques were composed primarily (91% to 97%) of fibrous tissue. Oil red O staining, polarized light microscopy, and electron microscopy revealed cholesterol deposits in the plaques and in the walls of coronary arteries, saphenous vein grafts, and aorta. Such deposits also were found in foam cells of histiocytic origin, fibroblasts in all four cardiac valves, and in Schwann cells of cardiac nerves.

Aged↗
PubMed1992

Endothelial fenestration of the alveolar capillaries in interstitial fibrotic lung diseases.

A light and electron microscopy study was performed on endothelial cells of alveolar capillaries in biopsied lung tissues obtained from 28 patients with interstitial fibrotic lung diseases, including idiopathic pulmonary fibrosis, sarcoidosis, hypersensitivity pneumonitis, chronic eosinophilic pneumonia, collagen vascular diseases and acute interstitial pneumonia. In the relatively early stages of acute interstitial pneumonia, hypersensitivity pneumonitis and other diseases, the cytoplasms of the endothelial cells appeared swollen and electron-lucent and occasionally showed degeneration and necrosis. Although mitosis was not evident in the endothelium at any disease stage, some capillary endothelial cells showed regeneration. Furthermore, although rarely, they showed obvious phenotypic transformation into diaphragmed fenestrae in some limited segments of fibrotic lungs in the 20 of the 28 patients examined. The frequency of endothelial fenestration seemed to be correlated with the degree of interstitial fibrosis along the alveolar walls. In such fibrotic lung tissues, cuboidal metaplastic cells of bronchiolar origin proliferated on the luminal side. The mechanism of endothelial fenestration in the alveolar capillaries is assumed to be comparable with cuboidal metaplasia of alveolar epithelial cells. The alveolar capillary endothelium is recruited from the bronchiolar capillaries via bronchopulmonary anastomoses unless endothelial repair occurs in situ. Regenerating endothelial cells move into the alveolar capillary tubes along the remnant sleeves of the basement membrane. New endothelial processes finally display their original fenestrated structure while secreting irregular fragments of basement membrane during implantation in the capillary beds.

Adult↗
PubMed1992

Endomyocardial biopsies in chronic chagasic cardiomyopathy. Immunohistochemical and ultrastructural findings.

Mononuclear cellular infiltrates and extensive fibrosis, with or without apical ventricular aneurysms, are the usual morphological findings in chronic chagasic cardiomyopathy. These lesions are thought to be mediated by immune phenomena rather than by continuing parasitic invasion of the heart. In the present report, we correlated clinical, immunohistochemical and ultrastructural findings in 30 endomyocardial biopsies from patients with chronic chagasic cardiomyopathy. In 12 of these biopsies, immunocytochemical techniques were used to identify and count leukocytes (common leukocyte antigen, CLA), T lymphocytes (UCHL-1 antibody) and B lymphocytes (L-26 antibody). The biopsy specimens showed variable degrees of myocardial hypertrophy and mononuclear infiltrates. No tissue forms of trypanosomes were found. The endocardium averaged 24 +/- 12.6 microns (mean +/- SD) in thickness. The mean myocyte diameter was 20 +/- 7.33 microns. The hearts were severely fibrotic containing a mean of 24.1 +/- 12.8% of fibrous tissue (range 8.2-49%), mast cells were scarce. Mononuclear cell infiltrates were found in 25 of the 30 biopsies. In 12 biopsies, immunohistochemical studies showed that the majority of the lymphocytes were T lymphocytes and associated with necrotic or degenerating myocytes. 10 of the 12 biopsy samples showed 5 or more CLA-positive mononuclear cells/high power field. In these 10 patients, T and B lymphocytes represented 32 and 13% of the total mononuclear infiltrating cells, respectively. The remaining cells were monocytes and macrophages.

Adult↗
PubMed1992

Dose-dependent smooth muscle cell proliferation induced by thermal injury with pulsed infrared lasers.

BACKGROUND: Recently, laser-heated and radio frequency-heated balloon angioplasty techniques have been proposed as a means to treat or minimize dissection and elastic recoil but have been associated with a high rate of clinical restenosis. Similarly, pulsed laser angioplasty techniques proposed to minimize thermal injury while ablating obstructing atheroma have failed to reduce clinical restenosis. Because "hot balloon" and pulsed laser angioplasty create both mechanical and thermal injury, it has been difficult to discern the cause of the smooth muscle cell (SMC) proliferation resulting in restenosis and whether such magnitude of proliferation is predictable and dose related. This study was undertaken to explore these issues. METHODS AND RESULTS: Localized thermal lesions accompanying efficient ablation were created with a pulsed Tm:YAG laser in nine rabbit aortas, which consistently led to a focal proliferation of SMC that filled the ablated region by 4 weeks. Transcutaneous Ho:YAG pulsed laser irradiation at multiple independent sites of 24 central rabbit ear arteries without ablation led to brief approximately 30 degrees C thermal transients and thermal damage to the artery wall resulting in significant neointimal proliferation by 3 weeks and a mean cross-sectional narrowing of 59 +/- 17% at a dose of 390 mJ/mm2. Acute and chronic responses to varying total energy deposition were studied by histology after the rabbits were killed at 2 hours to 4 weeks. Arterial segments midway between laser injuries were unaffected and served as internal controls. Neointimal proliferation at 3 weeks after laser injury exhibited a clear dose dependence. Mean cross-sectional narrowing increased from 34 +/- 10% to 85 +/- 15% as laser fluence increased from 240 mJ/cm2 to 640 mJ/cm2 (r = 0.84). Similarly, cross-sectional narrowing caused by SMC neointimal proliferation increased from 20 +/- 10% to 77 +/- 17% for a fixed surface irradiation as the depth of the most superficial arterial media decreased from 600 microns to 330 microns (r = 0.94). CONCLUSIONS: Thermal injury to the arterial wall is a potent stimulus for SMC proliferation and may necessitate reduction in laser or thermal energy used for angioplasty. Moreover, a dose-response relation exists between the degree of thermal injury and SMC proliferative response. Hence, this technique could be used as a practical model of restenosis suitable for screening therapies for inhibition of SMC proliferation.

Animals↗