Biomedical subjects

M Selman

Publications and source records attributed to M Selman.

At least 91 records · Page 5Linked to original sources

PubMed1990

Detection of antibodies against avian antigens in bronchoalveolar lavage from patients with pigeon breeder's disease: usefulness of enzyme-linked immunosorbent assay and enzyme immunotransfer blotting.

The study reported here evaluated the usefulness of the enzyme-linked immunosorbent assay (ELISA) in the detection of antibodies against pigeon antigens in the serum and bronchoalveolar lavage (BAL) of patients with clinical, radiological, and functional evidence of interstitial lung disease (ILD) with and without pigeon breeder's disease (PBD). The results were compared with those obtained by the simultaneous use of counterimmunoelectrophoresis (CIE) in the same patients. In PBD, ELISA detected antibodies against pigeon's sera in both serum and BAL in 100% of patients, while CIE failed to detect the antibodies in the serum of one patient and in most of the samples of BAL. In addition, we used enzyme immunotransfer blotting to determine the number of epitopes in pigeon serum recognized by antibodies present in serum and BAL. There was a heterogeneous response in both fluids, but the reaction pattern demonstrated that patient's sera recognize to-25 different pigeon epitopes. We conclude that ELISA is a highly sensitive and specific method for the detection of antibodies against pigeon antigens in the serum and BAL of patients with PBD and that the host response involves a great number of avian antigens.

Alveolitis, Extrinsic Allergic↗

PubMed1990

Pharmacological characterization of mediators and vagal influence in the acute allergic bronchoconstriction in guinea pigs.

The allergic bronchoconstriction in guinea pigs has been attributed mainly to the release of mast cell mediators. Histamine has been involved in the first minutes of the anaphylactic reaction and new-formed compounds in the subsequent response. In this asthma model the vagal influence has been sparsely investigated. In the present work we evaluated the pharmacological modification of the acute allergic bronchoconstrictor response in guinea pigs sensitized to ovalbumin through aerosol exposure. Pyrilamine (20 micrograms/kg), diethylcarbamazine (a lipoxygenase inhibitor, 10 mg/kg) and dexamethasone (4 mg/kg) each reduced the antigen-induced bronchoconstriction throughout the 30 min studied. Indomethacin (3.1 mg/kg) did not modify the response to the antigen. Atropine (2 mg/kg) plus bilateral vagotomy also diminished this response from 5 min onward. On the other hand, from 5 min ahead pyrilamine-resistant bronchoconstriction was partially inhibited by dexamethasone, and it was almost completely blocked during all of the response when atropine plus bilateral vagotomy were added to dexamethasone. Dipyridamole (an inhibitor of the adenosine uptake, 0.4 mg/kg) enhanced the bronchoconstriction, though this was significant only in the 2-5 min time-interval of the response. These results suggest that histamine and vagal influence play an important role in the whole response to antigen, that other mediators, probably leukotrienes, participate in this response from 5 min onward, and that adenosine could exert a potentiation effect on this response.

Adenosine↗

PubMed1990

Immunoregulatory abnormalities in patients with pigeon breeder's disease.

T-cell suppression induced by concanavalin-A (Con-A) and the prostaglandin suppressor system (PSS) were studied in 14 patients with pigeon breeder's disease (PBD), 12 and 10 asymptomatic breeders, and 8 controls. Our results showed that PBD patients display a significant decrease in T-cell-induced suppression (29.6 +/- 15.3% vs. 61.2 +/- 9.3% in controls p less than 0.05); whereas asymptomatic breeders respond heterogeneously: 5 showed decreased suppression and 7 were within the normal range obtained in controls. In contrast, the patients presented a higher PSS index compared with the other 2 groups, suggesting an inverse relationship between the 2 systems. These findings indicate that there are relevant differences between PBD patients, asymptomatic breeders, and normal subjects in some immune interactions, which may at least partially explain the characteristic cellular and humoral hyperreactivity observed in patients with this disease.

Adult↗

PubMed1990

Lack of local neurogenic involvement in the hyperreactivity induced by epithelium removal in guinea pig trachea.

Airway epithelium removal produces tracheobronchial smooth muscle hyperreactivity to different constrictor agonists. Aside from the loss of an epithelium-derived relaxant factor, other mechanisms such as production of local axon reflex could hypothetically be involved. In the present work we investigated the effect of nerve activity inhibition or ganglionic transmission blockade in the epithelium removal-induced hyperreactivity in guinea pig trachea. Tetrodotoxin, tetracaine or hexamethonium did not modify the enhanced sensitivity of denuded tracheas to histamine, suggesting that, at least under these experimental conditions, local axon or ganglionic reflexes are not involved.

Animals↗

PubMed1990

Effect of lung T lymphocytes on fibroblasts in idiopathic pulmonary fibrosis and extrinsic allergic alveolitis.

Increased fibroblast replication and interstitial collagen accumulation occur commonly in the interstitial lung disease that progress to fibrosis. The processes controlling lung fibrogenesis are not completely understood, however. This study was designed to analyse the influence of T lymphocytes from lung tissue obtained at open lung biopsy from four patients with idiopathic pulmonary fibrosis and four patients with extrinsic allergic alveolitis on fibroblast proliferation and collagen synthesis in vitro. Lung T cell supernatants from patients with both diseases induced a moderate but significant inhibition of human lung fibroblast cell line growth. In contrast, there was a clear difference in the effect of T cells from the two groups of patients in relation to collagen production. Lung T lymphocytes from all four patients with idiopathic pulmonary fibrosis produced a substantial increase in collagen synthesis (from 371% to 514% of control values), whereas T cells from three of the four patients with extrinsic allergic alveolitis induced a significant decrease in collagen production (to 35%, 36%, and 43% of control values); in the fourth case there was an increase in collagen synthesis but this was lower than that seen with T cells from any of the patients with idiopathic pulmonary fibrosis. Peripheral T cells from six patients and control subjects caused a small increase in fibroblast proliferation and no change in collagen synthesis. The findings suggest that at least two types of interaction occur between lung T cells and fibroblasts in these disorders. A variable degree of inhibition of cell proliferation is observed in response to lung T cell supernatants from patients with both idiopathic pulmonary fibrosis and extrinsic allergic alveolitis; a substantial increase in collagen synthesis is triggered by lymphokines from patients with idiopathic pulmonary fibrosis.

Adult↗

PubMed1990

Platelet-derived growth factor in idiopathic pulmonary fibrosis.

Fibrosis is a complex process involving an inflammatory reaction, fibroblast proliferation, and abnormal accumulation of interstitial collagens. Mononuclear cells are usually present in lung fibrosis. Activated monocytes and macrophages in culture have been shown to produce several growth factors including platelet-derived growth factor (PDGF). PDGF is a potent mitogen and chemoattractant for fibroblasts and smooth muscle cells and a stimulator of collagen synthesis. We have studied the expression of c-sis/PDGF-2 mRNA in lung tissues derived from five patients with idiopathic pulmonary fibrosis (IPF) and from four control individuals without IPF. Northern blot analysis of specimens obtained from four patients with IPF revealed the expression of the c-sis/PDGF-2 protooncogene. A control lung tissue without IPF did not express the c-sis protooncogene. In situ hybridization extended these studies demonstrating the expression of the c-sis mRNA in the five specimens with IPF but not in the four control specimens without IPF. The expression of c-sis mRNA was localized primarily in the epithelial cells. Invading alveolar macrophages also expressed c-sis mRNA. The expression of c-sis mRNA was accompanied by the expression of PDGF-like proteins in lung specimens with IPF but not in control lung specimens. These findings demonstrate the in vivo expression of the c-sis/PDGF-2 protooncogene and the production of PDGF-like proteins in the epithelial cells and macrophages of the fibrotic tissue. This localized and sustained production of PDGF-like mitogen may constitute an important contributing factor in the abnormal fibroblast proliferation and collagen production, events associated with pulmonary fibrosis.

Collagen↗

PubMed1990

Clubbing in hypersensitivity pneumonitis. Its prevalence and possible prognostic role.

To know the prevalence and prognostic significance of finger clubbing in hypersensitivity pneumonitis induced by avian antigen, this physical sign was evaluated in 82 patients who were followed up from 1 to 5 years (mean, 2.6 years). According to clinical, roentgenographic, and functional criteria, the patients were classified in one of three stages at admission as well as at least 1 year later. Digital clubbing was retrospectively recorded as present or absent by physical examination. Our results showed that 44 patients (51%) included in this study presented clubbing at the time of diagnosis. Sixteen of these patients presented with worsening of their lung disease, whereas only 5 of the 38 patients without clubbing incurred a worsening of their condition. This finding suggests that digital clubbing is frequent in pigeon breeder's disease and may help to predict clinical deterioration.

Adult↗

PubMed1989

Experimental pulmonary fibrosis induced by paraquat plus oxygen in rats: a morphologic and biochemical sequential study.

Changes in lung structure and collagen metabolism were studied at 1, 2, 3, 4, 6, and 8 weeks in a model of pulmonary fibrosis induced in rats with paraquat plus hyperoxia. Morphologic examination of the lungs revealed that the earliest lesions consisted of severe and irreversible endothelial and alveolar epithelial cell damage. Afterward, an inflammatory process took place, initially dominated by polymorphonuclear leukocytes and then by mononuclear cells, but with the constant presence of granulocytes. From the fourth week on there were fibroblast proliferation and a moderate increase of mast cells. In the early stages alveolitis was focal, but from the second week the lungs were diffusely affected with severe distortion of the architecture. Collagen content was moderately increased in the first 2 weeks and then showed a progressive increment until the end of the experiment. Collagen synthesis was significantly elevated from the fourth week, coinciding with interstitial fibroblast proliferation, although there were some animals that showed increased collagen production from the first week. Collagenolytic activity occurred in 3 stages: at 2 weeks there was increased collagen degradation, at 3, 4, and 6 weeks the values showed a trimodal behavior, and at 8 weeks almost all experimental rats presented an important decrease of collagenolysis. Thus, the development of lung fibrosis was associated first with increased rates of collagen synthesis and later with a decrease of collagen degradation.

Animals↗

PubMed1989

Lung collagenase inhibitors and spontaneous and latent collagenase activity in idiopathic pulmonary fibrosis and hypersensitivity pneumonitis.

In order to analyze the mechanisms involved in the decreased collagenolytic activity previously observed in interstitial lung fibrosis, we studied the inhibitory collagenase activity and the latent activable collagenase in lung samples from five patients with IPF, six with HP, and three control subjects. Our results showed that in both diseases, the inhibitor levels were significantly higher than in control subjects. Findings suggest that in IPF low amounts of collagenase plus excessive enzyme-inhibitors may be operating to decrease collagen catabolism. In contrast, HP lungs seem to contain adequate amounts of the enzyme but higher levels of inhibitors play a role in the abnormal degradation observed in some patients.

Adult↗

PubMed1988

Role of airway epithelium on the reactivity of smooth muscle from guinea pigs sensitized to ovalbumin by inhalatory method.

It has been demonstrated that the lack of epithelium in healthy airways from different species modifies the reactivity of tracheobronchial smooth muscle. In the present work we have investigated the effect of airway epithelium removal in tracheal chains from guinea pigs sensitized to ovalbumin by inhalatory route and unsensitized animals. We found that in both groups the mechanical removal of airway epithelium produced an increase in the tracheal sensitivity and maximum contractile response to histamine. The greatest responses were observed in epithelium-lacking sensitized tracheas. These findings, at least in vitro, support the idea that the damage of respiratory epithelium plays an important role in modulating the airway reactivity and this is more noteworthy in tracheal chains from previously sensitized guinea pigs.

Animals↗

PubMed1988

Collagen metabolism in experimental lung silicosis. A trimodal behavior of collagenolysis.

In spite of several studies, both in vivo and in vitro, the pathogenesis of silicosis remains unclear, mainly in those mechanisms related to fibrogenesis. In this study, we analyzed the concentration, biosynthesis, and degradation of collagen in silica-treated rats 7, 15, 30, 45, and 60 days after instillation. Our results showed a significant increase in collagen content and biosynthesis from the 15th day onward. However, our most remarkable finding was related to collagenolytic activity. In this sense, the silicotic rats presented a trimodal behavior: some animals showed an increased degradation, others had similar values to those of the controls, and others exhibited a decrease of collagenolytic activity. Altogether, these results suggest that collagen deposition in silicotic lungs is due to a rise in biosynthesis and, at least in some animals, to a decrease in degradation. Nevertheless, the steps of collagenolysis must be studied in more detail.

Animals↗

PubMed1988

Urinary thromboxane B2 as an indicator of acute rejection in lung allotransplantation.

The behavior of urinary thromboxane B2 (TXB2) during acute rejection of lung allotransplants was evaluated. Unmatched mongrel dogs were submitted to a left lung orthotopic allotransplantation (groups I and II), or a sham operation (group III). All animals had an initial significant elevation of TXB2 excretion due to surgical trauma; however, in sham-operated animals (group III) this elevation returned to basal levels after 3 days. All transplanted animals (groups I and II) had persistent TXB2 elevation with 2 important peaks on postop days 5 and 9. The elevated TXB2 excretion persisted in spite of immunosuppressive treatment with azathioprine and prednisone (group II). Rejection was followed by means of an objective grading system applied to chest roentgenograms taken on all animals. It was found that TXB2 levels correlated directly with the grade of radiographic changes seen, thus indicating degree of rejection. TXB2 can be useful as a noninvasive indicator for surveillance of lung allograft rejection.

Animals↗

PubMed1988

Lung collagen metabolism and the clinical course of hypersensitivity pneumonitis.

We studied lung collagen metabolism in 18 patients with hypersensitivity pneumonitis to determine if changes at this level could explain the different clinical courses followed by these patients. Collagen concentration, biosynthesis and degradation were measured in lung tissue samples obtained before treatment. Four patients healed, eight improved and six did not improve or worsened. All patients who healed showed an important increase in collagenolysis; patients who improved had normal or high values, but significantly less than those obtained in patients who healed. Finally, five out of the six patients who did not improve or worsened had a significant decrease in degradation. These findings support the notion that a diminution of local collagenolysis may play a role in the progression to fibrosis in some patients with hypersensitivity pneumonitis and can also be a useful tool to predict the prognosis of this disease.

Adolescent↗

PubMed1987

Subpopulations of T cells in lung biopsies from patients with pigeon breeder's disease.

Monoclonal antibodies were used to determine surface phenotypes of T cells in tissue obtained by open lung biopsies from patients with chronic hypersensitivity pneumonitis (pigeon breeder's disease). The results indicate that an increased number of suppressor/cytotoxic cells is present in these patients when compared with the number of helper/inducer cells. These findings, which were present within the interstitium, are consistent with those found in bronchoalveolar lavage of patients with this disease. In addition, in two-thirds of the patients there was a greater total number of helper and suppressor cells than the total count for Pan T cells. A possible interpretation of these findings might be the presence of both markers in the same cell.

Adult↗

PubMed1987

Increase of HLA-DR7 in pigeon breeder's lung in a Mexican population.

The phenotypes of the major histocompatibility complex, loci A, B, C, and DR, were studied in 48 patients with hypersensitivity pneumonitis induced by avian antigen (pigeon breeder's lung) and the results were compared to those obtained from 200 normal subjects of similar ethnic background. Furthermore, we analyzed the delta values of the observed and expected frequencies in the deduced haplotypes of the affected population. Our results showed a significant increase of the antigen HLA-DR7 (corrected P less than 0.001) in patients with pigeon breeder's lung and an equally important difference in the delta values of the haplotypes A1-B8, A25-B14, B35-DR4, and B4-DR5. In addition, the phenotypes of locus DQ were analyzed in 21 patients and 20 controls and no apparent differences were observed. These results suggest that a multifactorial genetic susceptibility associated at least in part with the major histocompatibility complex plays in important role in the development of this disease.

Adult↗

PubMed1987

Increase of biosynthesis and degradation of collagen in normal lungs induced by soluble factors obtained from experimental pulmonary silicosis.

We have studied the effects of soluble factors obtained from rat lungs with experimentally-induced pulmonary fibrosis of 2 months duration on the in vitro rates of biosynthesis and degradation of collagen in normal rat lung preparations. Factors soluble in phosphate-buffered saline were prepared from the minced lungs of normal controls and of silicotic animals. The in vitro rate of collagen biosynthesis of normal rat lung explants was measured as the rate of incorporation of radioactive proline into total and collagenous protein. The in vitro rate of collagen degradation in normal rat lung homogenates was measured as the rate of release of hydroxyproline-containing materials of less than 100,000 daltons to the supernatant. Our results suggest that in this experimental model of pulmonary fibrosis there are soluble factors that stimulate both collagen biosynthesis and collagen degradation in in vitro preparations of normal rat lung.

Animals↗

PubMed1986

Concentration, biosynthesis and degradation of collagen in idiopathic pulmonary fibrosis.

Despite several studies both in vitro and in vivo, the pathogenesis of pulmonary fibrosis is unclear and some findings related to the biochemistry of collagen are controversial. Collagen metabolism was studied in 11 patients with idiopathic pulmonary fibrosis and in six control subjects. There was an increase in collagen concentration (mean 327 (SD 76) compared with control values of 185 (18) micrograms/mg dry weight, p less than 0.001), normal values for biosynthesis (mean 2.2% (0.8%) v 2.08% (0.5%), and a noteworthy decrease in collagenolytic activity (mean 0.07 (0.04) v 0.23 (0.04) micrograms of collagen degraded per mg of collagen incubated, p less than 0.001). These results suggest that an alteration in enzymatic breakdown of collagen plays an important role in the maintenance and progression of interstitial fibrosis in this disease.

Adult↗

PubMed1986

D-penicillamine in the therapy of fibrotic lung diseases.

We studied 12 patients with pulmonary fibrosis treated with D-Penicillamine in an attempt to regulate the collagen metabolism that is seriously affected in this group of patients. After six years follow-up we found a 33% survival rate compared to a 5% survival rate in patients treated with corticosteroids (p less than 0.01). Functional respiratory tests as well as quality of life were improved in all patients. No side effects attributable to D-Penicillamine were detected probably due to the fact that we used smaller doses than those reported in the treatment of other diseases of the connective tissue. We conclude that D-Penicillamine can be a useful alternative drug in the therapy of patients with pulmonary fibrosis.

Humans↗