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D K Madtes

Publications and source records attributed to D K Madtes.

28 records · Page 2Linked to original sources
PubMed1993

Expression of transforming growth factor-alpha in mid-gestation human fetal lung.

Transforming growth factor-alpha (TGF-alpha), a member of the epidermal growth factor (EGF) family, is a potent mitogen for several cell types. To investigate the possible role of TGF-alpha in the development of midgestation human fetal lung, we studied its distribution with immunohistochemistry and determined levels of steady-state TGF-alpha mRNA by Northern analysis of cellular RNA isolates from lung. Lung was obtained from fetuses at 10 to 22 wk of gestation (n = 14) and immunostained for TGF-alpha. TGF-alpha was localized in epithelial cells at all gestational ages examined. Immunostaining was particularly prominent in bronchiolar epithelial cells. TGF-alpha immunoreactivity was also associated with arterial smooth muscle cells, as well as with nerves. Occasional chondrocytes were also associated with TGF-alpha immunoreactivity. Total cellular RNA was isolated from lung tissue obtained from additional fetuses at gestational ages 10 to 24 wk (n = 22). TGF-alpha mRNA was present in RNA extracts of all fetal lungs studied. We conclude that TGF-alpha is probably produced in human fetal lung during mid-gestation. The prominent immunostaining of bronchiolar epithelial cells for TGF-alpha is consistent with its playing a role in distal airway formation.

Antibodies, Monoclonal↗
PubMed1989

Obstructive lung disease after allogeneic marrow transplantation. Clinical presentation and course.

To describe the clinical presentation and progression of obstructive lung disease after marrow transplantation, we examined a sequential sample of 35 patients who had allogeneic marrow transplantation between January 1980 and January 1987, were 16 years or older, had normal pulmonary function tests before transplantation, and developed airflow obstruction defined as FEV1/FVC less than 70% and FEV1 less than 80% predicted 50 days or more after transplantation. Cases were selected from 1029 adult (older than 16 years) patients who underwent allogeneic marrow transplantation during the same period. Patients with airflow obstruction presented with symptoms of cough, dyspnea, or wheezing, or a combination. In 80% the chest radiograph was normal. Airflow obstruction was diagnosed within 1.5 years after transplantation in 33 of 35 patients. Clinical, extensive, chronic graft-versus-host disease was present in 24 patients. Only 4 patients had a complete response to primary therapy of chronic graft-versus-host disease. Serum IgG and IgA levels were decreased in 15 and 25 patients, respectively. The FEV1 declined rapidly (decrease in FEV1 greater than 30% between tests) in 21 patients, but 14 patients with slowly progressive or reversible disease were identified. Mortality was 65% at 3 years after transplant, a significantly higher value (P = 0.016) than the 3-year mortality rate of 44% in a comparison group of 412 concurrent patients with chronic graft-versus-host disease who were 16 years or older, survived more than 80 days after transplantation, and had normal pulmonary function. We concluded that obstructive lung disease after marrow transplantation may be variable with respect to time of onset and rate of progression. Obstructive lung disease was frequently associated with serum immunoglobulin deficiency and clinical, extensive, chronic graft-versus-host disease that was not readily responsive to treatment. Mortality was high but long-term survivors were identified.

Adolescent↗
PubMed1989

Pulmonary venoocclusive disease following bone marrow transplantation.

We report two cases of pulmonary venoocclusive disease (PVOD) in children with acute lymphoblastic leukemia treated by marrow allograft transplantation following conditioning with high-dose 1-3 bis chloroethyl-1 nitrosourea (BCNU), etoposide (VP-16), and cyclophosphamide (Cy). Both patients developed symptomatic pulmonary hypertension documented by right heart catheterization. Open-lung biopsy of one patient demonstrated PVOD evident even on frozen sections stained with hematoxylin and eosin. High-dose methylprednisolone was associated with significant clinical improvement in both patients. Pulmonary symptoms resolved in one patient who subsequently died in leukemic relapse. PVOD resolved in the other patient, only to recur when steroids were discontinued and then again respond to reinstitution of therapy. More aggressive therapy for malignant diseases may increase the incidence of PVOD. Prompt recognition of its subtle clinical and histological manifestations allows early institution of steroid therapy, which may be beneficial.

Bone Marrow Transplantation↗
PubMed1988

Induction of transforming growth factor-alpha in activated human alveolar macrophages.

The early monocyte infiltration observed in normal wound repair and in a number of pathologic processes precedes the epithelial and connective tissue proliferative responses, suggesting that the monocyte/macrophage may be an important source of growth factors for these tissues. In culture, activated macrophages secrete growth factors active on fibroblasts, smooth muscle, endothelium, and epithelium. This report demonstrates that activated human alveolar macrophages express the gene for transforming growth factor-alpha (TGF-alpha) in an inducible manner and secrete a factor into the culture medium that is functionally and immunologically identical to TGF-alpha. Two different molecular species of TGF-alpha activity (approximately 8,500-12,000 and 28,500 daltons) are identified in macrophage-conditioned medium. These observations establish the macrophage as a diploid human cell capable of synthesizing and secreting TGF-alpha. The activated macrophage therefore represents a cellular source of a mitogenic factor that is potentially important in epithelial proliferation and repair.

Animals↗
PubMed1987

Expression and secretion of type beta transforming growth factor by activated human macrophages.

Alveolar macrophages activated with concanavalin A and peripheral blood monocytes activated with lipopolysaccharide secrete type beta transforming growth factor (TGF-beta). There is minimal TGF-beta secretion in unactivated monocytes, even though TGF-beta mRNA is expressed in these cells at a level similar to that in activated, lipopolysaccharide-treated cultures. U937 lymphoma cells, which have monocytic characteristics, also express mRNA for TGF-beta. Freshly isolated monocytes, both control and lipopolysaccharide-treated, secrete an acid-labile binding protein that inhibits TGF-beta action. We conclude the following: (i) that expression of TGF-beta mRNA is unrelated to monocyte activation, (ii) that secretion of TGF-beta is induced by monocyte activation, and (iii) that cosecretion of TGF-beta and its monocyte/macrophage-derived binding protein may modulate growth factor action. In contrast, monocytic expression of other growth factor genes, such as the B chain of platelet-derived growth factor, is not constitutive and requires activation.

Cell Line↗
PubMed1985

A significant part of macrophage-derived growth factor consists of at least two forms of PDGF.

The macrophage has been suggested to be responsible for the connective tissue cell proliferation that accompanies most chronic inflammatory responses. One of the secretory products of activated macrophages is MDGF, a growth factor (or factors) for fibroblasts, 3T3 cells, smooth muscle, and vascular endothelium. This report demonstrates that a significant portion of the mitogenic activity for 3T3 cells secreted by cultured human alveolar and peritoneal macrophages is due to a molecule (or molecules) similar to platelet-derived growth factor (PDGF). Two size classes (approximately 37,000-39,000 and 12,000-17,000 daltons) of mitogenically active PDGF-like molecules are detected by two criteria--antigenic similarity with PDGF and ability to compete with 125I-PDGF for high-affinity binding to the PDGF receptor. The presence of mRNA for the B chain of PDGF is demonstrated by Northern analysis, and de novo synthesis of these molecules by activated macrophages is shown by immunoprecipitation of 35S-labeled proteins with anti-PDGF IgG.

Animals↗
PubMed1985

Bronchiolitis obliterans caused by Legionella pneumophila.

A diabetic patient presented with symptoms and laboratory findings compatible with atypical pneumonia. Despite appropriate antibiotic therapy, his dyspnea, arterial oxygenation, and chest roentgenographic findings worsened. Because the patient had a history of homosexual contact, an open lung biopsy was obtained to morphologically define the tissue reaction and to search for a specific etiology. Histologic examination showed bronchiolitis obliterans but did not demonstrate a cause. Legionnaires' disease was subsequently diagnosed on the basis of a fourfold rise in indirect fluorescent antibody titer. This case report demonstrates that Legionella pneumophila may induce lung injury with bronchiolitis obliterans. Such patients may benefit from corticosteroid treatment.

Biopsy↗
PubMedDate not supplied

Effects of platelet-derived growth factor isoforms on human lung fibroblast proliferation and procollagen gene expression.

Platelet-derived growth factor (PDGF), a potent mitogen for fibroblasts, is a potentially important cytokine in the pathogenesis of fibroproliferative disorders of lung. Different isoforms of PDGF include a heterodimer composed of A and B chains and homodimers composed of A or B chains. The biological significance of the different isoforms is unknown, but they have been shown to differ in their mitogenic potency in some systems. Their effects on other fibroblast functions have not been fully examined. We undertook this study to determine the effect of PDGF isoforms on human lung fibroblast proliferation and procollagen synthesis. Cultured lung fibroblasts (IMR-90, WI-38, GeNA) were incubated in the presence of varying concentrations of highly purified PDGF-AB obtained from platelets or recombinant PDGF-AA or -BB homodimers. Incorporation of [3H]thymidine was determined as a measure of mitogenic activity. Fetal lung fibroblasts (IMR-90, WI-38) and an adult fibroblast strain (GeNA) responded similarly to the different isoforms, with maximum mitogenic activity observed at 5-10 ng/mL. Cell cycle analysis using three additional normal adult lung fibroblast strains indicated that all PDGF isoforms stimulated similar proportions of cells to cycle over a 7-day period. Fibroblast procollagen synthesis, measured after pulse labeling with [3H]proline, was not increased even at concentrations of the PDGF isoforms that were maximally mitogenic. Moreover, steady-state levels of alpha 1(I) and alpha 1(III) procollagen mRNA levels, determined by northern analysis and dot blot hybridization, were not changed after exposure to any of the PDGF isoforms. While all PDGF isoforms are potent mitogens for fetal and adult lung fibroblasts, it was concluded that they do not directly stimulate procollagen gene expression or procollagen synthesis in vitro. The results suggest that PDGF isoforms are potentially important mitogens for lung fibroblasts, but other factors are likely to be involved in the stimulation of fibroblast procollagen synthesis that is observed in fibroproliferative disorders of lung.

Cell Cycle↗