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Biomedical subjects

R M Tuder

Publications and source records attributed to R M Tuder.

72 records · Page 4Linked to original sources
PubMed1994

Interleukin-1 receptor antagonist treatment reduces pulmonary hypertension generated in rats by monocrotaline.

Chronic pulmonary hypertension is associated with significant vascular remodeling. We demonstrated recently in the monocrotaline (MCT) and chronic hypoxia rat models of pulmonary hypertension that treatment with platelet-activating factor (PAF) antagonists inhibited the development of chronic pulmonary hypertension. PAF and other lipid mediators interact with interleukin-1. We postulated that chronic treatment with a recombinant human interleukin-1 receptor antagonist (IL-1ra) would inhibit development of chronic pulmonary hypertension in animal models. Rats were either injected with (60 mg/kg) MCT or exposed to a stimulated high altitude of 16,000 feet; half of the animals were treated with twice-daily injections (2 mg/kg) of IL-1ra. At 3 wk after MCT injection or 3 wk of hypoxic exposure, pulmonary artery pressure and right heart ventricle weight/(left ventricle and septum weight), RV/(LV + S), were measured. IL-1ra treatment reduced pulmonary hypertension and right heart hypertrophy in the MCT model, but not in the chronic hypoxia model. Measurement of lung homogenate IL-1 alpha by radioimmunoassay showed elevated levels in the MCT-treated rats throughout the 3-wk observation period. IL-1ra treatment reduced the levels of IL-1 alpha in lung tissue in most of the MCT-treated rats. MCT treatment was also associated with an increase in lung mRNA for IL-1 alpha, IL-1 beta, and IL-1ra. Immunohistology, using an antibody against rat IL-1 alpha, revealed staining of alveolar structures and of vascular and bronchial smooth muscle. In situ hybridization using a human IL-1 alpha cDNA probe demonstrated increased expression of the IL-1 alpha gene in the lung cells after endotoxin or MCT treatment. Northern blot analysis demonstrated low-level expression of IL-1 alpha mRNA in extracts of normal rat lung and increased expression after endotoxin or MCT treatment. We conclude that chronic treatment with human IL-1ra inhibited the development of pulmonary hypertension in the inflammatory (MCT) model, but not in the chronically hypoxic rats. This result indicates that IL-1 participates in the pathogenesis of some forms of pulmonary hypertension.

Animals↗
PubMed1994

Exuberant endothelial cell growth and elements of inflammation are present in plexiform lesions of pulmonary hypertension.

The plexiform lesion in primary pulmonary hypertension is a glomeruloid structure forming channels in branches of the pulmonary artery. These lesions have been considered an abnormal growth of modified smooth muscle cells. We present immunohistochemical evidence in 10 cases of plexogenic pulmonary hypertension that the plexiform channels and the concentric obliterative arteriopathy associated with these channels represent abnormal growth of factor VIII-related antigen-positive endothelial cells. In addition, these cells strongly expressed vimentin, a growth- and differentiation-related intermediate filament. Morphologically and immunohistochemically, the lesions resembled the neovascularization associated with the brain tumor glioblastoma multiform. Furthermore, we noted an exclusively perivascular inflammatory cell infiltrate (but no vasculitis) in seven of the 10 cases with plexogenic arteriopathy composed of T cells, B cells, and macrophages. Our findings indicate that the plexiform lesion may result from a deregulated growth of endothelial cells. The presence of perivascular inflammatory cells suggested that cytokines and growth factors may further influence the development of the plexiform lesion.

Adult↗
PubMed1994

Agarose infiltration improves morphology of cryostat sections of lung.

BACKGROUND: Optimal morphology and immunohistochemistry of the lung requires the organ to remain fully distended. When the lung is prepared for frozen sections, especially during the stage of cryoprotection, liquid fixatives leak out and the lung tends to collapse. We sought to develop a new technique to improve the morphology of frozen sections of the lung while facilitating tissue handling and immunoreactivity. EXPERIMENTAL DESIGN: Human, fetal sheep and adult rat lungs were distended with 1% low temperature melting agarose and vessels were perfused with a 1% paraformaldehyde solution. RESULTS: The agarose infiltration permitted easy handling of the lung tissue, and maintained lung architecture during cryoprotection. Agarose infiltration and paraformaldehyde fixation provided excellent morphology, that was comparable to paraffin-embedded tissue. The structural preservation was especially noticeable with human lung that remained well distended with the agarose technique. Because of the mild fixation and good morphology, precise localization of antigenic sites was possible for the surfactant proteins SP-A, SP-C and SP-D, cytokeratin, and alveolar macrophage markers. CONCLUSIONS: This procedure can improve special fixation and embedding protocols for lung immunocytochemistry and immunofluorescence.

Animals↗
PubMed1992

Endotoxin after gut ischemia/reperfusion causes irreversible lung injury.

We have recently reported that 45 min of gut ischemia causes moderate 125I-albumin lung leak at 6 hr of reperfusion which was reversed at 18 hr. Our purpose was to determine the effect of a second insult, low dose endotoxin (LPS, 2.5 mg/kg), given 6 hr after gut ischemia/reperfusion (I/R) on this lung injury as assessed by 125I-albumin leak, neutrophil influx (myeloperoxidase assay, MPO), histopathology, and mortality. Rats were randomized to either sham laparotomy (LAP) or 45 min of superior mesenteric artery occlusion and 6 hr later were treated with LPS or saline. At 18 hr reperfusion the lungs were harvested, assayed for 125I-albumin leak and MPO, and microscopically examined by an unbiased observer after routine H&E staining. We observed that LPS increased lung neutrophil levels both with or without gut I/R. However, only the combined insult (I/R + LPS) increased 125I-albumin leak at 18 hr of reperfusion. Lung histology confirmed that the sequential combination of I/R + LPS caused marked interstitial edema and neutrophil sequestration accompanied by alveolar edema, hemorrhage, and fibrinous exudate, while I/R or LAP + LPS did not. The mortality rate of I/R + LPS was 39% which was significantly higher than LAP alone (0%), gut I/R alone (0%), or LAP + LPS (4%). In conclusion, a delayed exposure to low dose endotoxin converts moderate gut I/R-induced lung dysfunction into advanced organ failure.

Albumins↗
PubMed1992

Vulvar destruction by malignant lymphoma.

Two cases of vulvar and perineal destruction by malignant lymphoma are described. The first case was of an untreated 4-year-long vulvar destruction due to a kappa-positive lymphoplasmacytic lymphoma that ultimately resulted in the death of the patient. The second patient had involvement of the vulva and perineum by an angiocentric small and large mixed-cell lymphoma. Aggressive chemotherapy induced regression and healing of the lesions in the second case. Delayed diagnosis and inappropriate management of lymphomas in the vulva may lead to widely destructive disease of the lower female genital tract.

Adult↗
PubMed1990

Cyclic adenosine monophosphate levels and the function of skin microvascular endothelial cells.

The maintenance of the normal epithelioid morphology of human dermal microvascular endothelial cells (MEC) grown in vitro depends strongly on the presence of factors that increase intracellular levels of cyclic AMP. Complete removal of dibutyryl cAMP and isobutylmethylxanthine (IMX) from the growth medium results in a progressive transition from an epithelioid to a spindle-shaped cell line. This transition cannot be reversed by the readdition of dibutyryl cAMP and IMX to the growth medium or by addition of agonists that increase cAMP levels. Spindle-shaped MEC lose the ability to express Factor VIII rAG and DR antigens and to bind peripheral blood mononuclear leukocyte (PBML). Ultrastructural analyses of transitional cells and spindle-shaped cells show decreased numbers of Weibel-Palade bodies in transitional cells and their complete absence in spindle-shaped cells. Interferon-gamma alters several functional properties of both epithelioid and spindle-shaped cells. In the absence of dibutyryl cAMP it accelerates the transition from epithelial to spindle-shaped cells, whereas in the presence of cyclic AMP interferon-gamma increases the binding of PBMLs to both epithelioid and spindle-shaped MEC and the endocytic activity of the endothelial cells. These results suggest that cyclic AMP is an important second messenger in the maintenance of several key functions of microvascular endothelial cells. Factors that influence the levels of this messenger in vivo can be expected to influence the angiogenic and immunologic functions of the microvasculature.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Adult cutaneous hemangiomas are composed of nonreplicating endothelial cells.

Thirty-four human "cherry" dermal hemangiomas were studied by electron microscopy, immunohistochemistry, and cell culture to assess the neoplastic nature of these lesions. Electron microscopy of nine hemangiomas revealed a pronounced thickening of the basement membrane (0.6 to 14 micron) in 93% of the total 158 vascular structures examined within the lesions. This increase was caused mainly by multiple layers of basal lamina, which were irregular in outline and frequently associated with pericytes. Basement membrane changes were present both in the periphery of the hemangiomas, as well as in the center of the lesions. Immature vessels could not be identified and mitoses were absent in all endothelial cells. Using an immunohistochemical marker (Ki67) specific for proliferating cells in G2 and S phases, positive staining was not found in the endothelial cells lining the hemangiomatous vessels, whereas basal epidermal keratinocytes in the same preparations and cultured microvascular endothelial cells expressed the antigen. Endothelial cells of nine hemangiomas did not stain with an activation-related antibody (E12) specific for endothelial cells. When endothelial cells from 14 hemangiomas were isolated and cultured under conditions that support the growth of normal human skin microvascular endothelial cells, the cells of hemangiomatous origin failed to grow. We conclude that the adult hemangiomas may not be true neoplasms, but a tissue overgrowth composed of mature vessels resembling dermal venules, lined by endothelial cells with virtually no turnover.

Adult↗
PubMed1986

Mycobacterial coronary arteritis in a heart transplant recipient.

A case of mycobacterial vasculitis in a chronically rejected transplanted heart is described. The coronary arteries were the only vessels involved by mycobacteria, although the patient had a generalized infection. The process of chronic rejection, with persistent injury to the intimal vascular lining of a transplanted organ, may lead to defects in the endothelial cell barrier and thus facilitate infiltration of a vessel wall by acid-fast bacilli.

Arteritis↗
PubMed1986

Malignant disease of the pleura: a histopathological study with special emphasis on diagnostic criteria and differentiation from reactive mesothelium.

In order to define the histopathological criteria for the diagnosis of malignant neoplasm involving pleura, we studied 11 pleurectomy specimens containing undoubted malignant cells. The most important feature for a diagnosis of malignancy was the pattern of neoplastic infiltration of the fibrous sub-pleural tissue. These criteria were subsequently applied in a re-analysis of 76 pleural needle biopsies with a diagnosis of cancer. The patterns most frequently seen were a multi-pronged growth of at least four clusters of atypical cells in the fibrous sub-pleural tissue, a solid pattern with a large collection of atypical cells and a confluent one where large numbers of small clusters of atypical cells appeared almost fused in the stroma. Less frequently, malignant cells covered the surface of fibromuscular tissue, or were found in an intravascular or intramuscular location, but often associated with any of the three main patterns. Five needle biopsies were considered suspicious and 11, considered benign, contained a prominent mesothelial reaction. The benign control cases showed mesothelial cells mainly in a peripheral growth pattern or as clusters of cells interspersed with fibrin, without any mitotic activity; granulation tissue and lympho-histiocytic infiltrates were more frequently seen in the control group.

Adolescent↗
PubMed1985

Myocardial infarct in disseminated mucormycosis: case report with special emphasis on the pathogenic mechanisms.

A case of myocardium infarction in generalized mucormycosis is reported in a patient suffering from chronic renal failure and receiving a cadaver kidney transplant. At autopsy we found a recent necrotic myocardium, coronary vessels occluded by mucor hyphae and a striking absence of inflammatory cells, chiefly neutrophils. Ultrastructural studies revealed thick-walled fungus that participate in the thrombus and cross the coronary artery in a 'corkscrew' pattern, without important cellular degeneration. Thin-walled irregularly branching structures were observed occluding the microcirculation of still preserved cardiac areas. These structures could be originated from the fungus cells that had lost their thick laminated wall, leaving the plasmatic membrane as external coat. Special emphasis is given to the relation between the poor coronary vascular protection against mucormycosis and the neutrophilic disfunction. The lungs are the main site of primary infection. This disease is underdiagnosed in vivo and leads always to death.

Adult↗
PubMed1985

Pathology of the human pulmonary paracoccidioidomycosis.

Lungs of twelve patients with chronic paracoccidioidomycosis (Pb) were studied in an attempt to understand the pathogenesis of the pulmonary disease. Ribbons of the lung parenchyma including the hilar region and directed towards apical, basal and lateral regions were subdivided into sections from the hilar, intermediate and peripheral segments. The following histopathological reactions directly or indirectly related to P. brasiliensis were described and analysed in relation to the number of slides studied and the pulmonary region involved: pneumonic reaction; early granulomatous formation; mature and healed granulomata; mixed pattern (early and mature granuloma in the same pulmonary area visualized in the slide); pulmonary fibrosis. It was concluded that chronic pulmonary Pb is a recurrent disease affecting equally both lungs. Fibrosis was connected mainly with the progressive evolution of the granulomata towards cicatrization and to a lesser degree probably to a direct induction by the fungi. Based chiefly on the tendency of the fibrosis to run around bronchi and to make up septa interconnecting bronchi and vessels it was hipothesized that these findings were the result of a previous chronic specific lymphangitis by the fungi. Hilar fibrosis would be the result of this lymphangitis and/or of the progression of the specific granulomatous reaction seen in the hilar lymph nodes. Non specific forms of arteritis and areas of destructive emphysema related to granulomatous inflammation and fibrosis were described. Three cases developed pulmonary hypertension.

Arteritis↗
PubMed1984

Primary semimalignant Schwannoma of the liver. Light and electron microscopic studies.

The light and electron microscopy study of a so-called low grade or semimalignant Schwannoma in the liver of a 74 year-old white man without von Recklinghausen's disease is reported. The diagnosis relied on the histological findings of numerous moderately pleomorphic fusiform cells with hyperchromatic nuclei, areas of necrosis, the local infiltrative pattern with absence of metastasis at autopsy, the huge size (21 X 12 X 8 cm) and the clinical data of rapid growth pattern associated with marked body weight loss. The proper identification in surgical specimens of this kind of neoplasias would lead to more appropriate therapeutic approach.

Aged↗
PubMedDate not supplied

Cytomegalovirus infection amplifies class I major histocompatibility complex expression on cultured human endothelial cells.

Cytomegalovirus infection, a common complication in immunosuppressed graft recipients, bears an adverse impact on graft survival. Cytomegalovirus enhances the expression of the monotypic determinants of the class I major histocompatibility complex molecule by the endothelium, possibly rendering the endothelial cells more immunogenic and prone to attack by the allogeneic lymphocytes. In the present study, we focused on the effect of cytomegalovirus on the endothelial cell expression of different class I genes, on the relation between the extent of endothelial cell infection and the class I effect, and on the time course of the class I changes induced by the cytomegalovirus infection. Cytomegalovirus infection of primary cultures of human umbilical vein endothelial cells augmented the expression of the A2, A3, and B7 class I major histocompatibility complex genes when compared with uninfected cells. beta 2 microglobulin upregulation by the infected cells paralleled the changes in specific class I expression; this effect was significant only after 7 days after infection. Double immunocytochemical staining and fluorescence-activated cell sorter analysis revealed that the class I enhancement was uniform throughout the umbilical vein endothelial cell monolayer and not restricted to the cells that expressed cytomegalovirus early or late antigens. Ultraviolet-inactivated supernatants from infected umbilical vein endothelial cell did not increase class I expression on uninfected cells. In conclusion, cytomegalovirus might affect graft survival by amplifying the changes in class I expression beyond the sites of viral replication.

Antibody Specificity↗