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Biomedical subjects

M Selman

Publications and source records attributed to M Selman.

At least 73 records · Page 4Linked to original sources

Characterization of an inhibitory seric factor from tuberculosis anergic patients that acts on non-adherent PPD reactive cells.

Non-adherent cells from PPD+ tuberculosis patients (TBP PPD+) and from healthy individuals treated with whole tuberculosis anergic immune sera or with its protein A-Sepharose IgG fraction, or with sera fraction separated by PPD-Sepharose chromatography, were submitted to immunofluorescence assays. Anti-human IgG or IgM FITC-conjugate were used to reveal the assays, and results were expressed by a fluorescence percentage or fluorescence index. The presence of IgG over the surface of PPD+ non-adherent cells was detected. High fluorescence percentages were observed only in those PPD+ cells treated with whole anergic serum or with its IgG fraction. Positive fluorescence index values were obtained only in those PPD+ cells treated with anergic serum, meanwhile fluorescence index was always negative when non-bound fractions from PPD-Sepharose were used. Results suggest that non-adherent population are the cell targets for the serum inhibitory factor, which previously has been detected to inhibit antigen response in PPD reactive cells and, point out the specific behavior of this factor, since it was eliminate by PPD-Sepharose chromatography. The IgG nature of the factor was demonstrated by SDS-PAGE and immunoelectrophoresis.

Adolescent↗

Leukotriene C4 upregulates collagenase expression and synthesis in human lung fibroblasts.

Leukotriene C4 (LTC4), a mediator generated by a variety of inflammatory cells, participates in several physiological and pathological processes. It has been shown that LTC4 stimulates collagen synthesis by fibroblasts, suggesting a role in collagen turnover. However, the possible effect of this mediator on collagen degradation has not been examined. In this study we explored the role of LTC4 in the modulation of fibroblast interstitial collagenase and TIMP-1. Confluent cultures of three human normal lung fibroblast cell lines, and one derived from idiopathic pulmonary fibrosis (IPF) were exposed to LTC4 0.1, 1 and 10 nM, and to IL-1 beta as positive control. Collagenase and TIMP mRNAs expression were analyzed by Northern blot followed by densitometric scanning. Immunoreactive procollagenase was detected by immunoblot, and collagenase activity was measured using [3H]collagen. Our results showed that LTC4 enhanced several-fold collagenase mRNA expression in collagenase-producing fibroblasts, and induced the expression of the enzyme mRNA in collagenase-nonproducing fibroblasts, both in normal and IPF derived cell lines. LTC4 1 nM induced the highest response. Collagenolytic activity and immunoreactive collagenase paralleled collagenase mRNA expression. Interestingly, simultaneous exposure of fibroblasts to LTC4 plus IL-1 failed to show additive effects. Moreover, in two cell lines the combination resulted in a decrease of collagenase mRNA expression compared with both mediators separately. TIMP mRNA levels were not significantly modified by LTC4, nor IL1 beta. Our findings suggest that LTC4 plays a role in the modulation of fibroblast collagenase, and it may participate in extracellular matrix remodeling during lung inflammation.

Collagenases↗

Cellular source of collagenase and TIMP-1 in carrageenin-induced granuloma.

We have examined the occurrence and cellular localization of interstitial collagenase and TIMP-1 mRNAs in a model of granuloma induced by carrageenin in guinea pigs. Granulomas were studied at 4, 7, 10, and 14 days after carrageenin injury using a combined protocol for in situ hybridization and immunofluorescence. Anti-vimentin monoclonal antibody was used to identify fibroblasts. Avidin-FITC and Texas red horse antimouse IgG were employed for detection of probes and antibody, respectively. Our results showed that during the extracellular matrix deposit phase (4 and 7 days), interstitial collagenase and TIMP-1 mRNAs were expressed only by fibroblasts as demonstrated by the colocalization of mRNA and vimentin. By contrast, during the initiation of the resorptive phase (10 and 14 days), fibroblasts and vimentin-negative cells, probably macrophages, expressed collagenase and TIMP-1. This study suggests that fibroblasts are the cell type expressing interstitial collagenase and TIMP-1 mRNA during all phases of the evolution of carrageenin granuloma and that macrophages, by contrast, express the mRNA for the enzyme and the inhibitor exclusively in the degradative phase.

Animals↗

[Evaluation of cholecystectomy by celioscopy. Apropos of a series of 500 operated patients in a general hospital unit].

A series of 500 patients who underwent laparoscopic cholecystectomy is reported. The mean duration of the operation was 46 minutes when completed laparoscopically and 117 minutes when converted to laparotomy. The conversion rate was 10%, and the reoperation rate 2.22%. There were 5 problems related to the bile ducts (1%) including 2 lesions of the common bile duct (0.44%) with only in 21 cases. In one, a stone in the common duct was extracted laparoscopically. Mean hospitalization was 5.5 days. For us, laparoscopic cholecystectomy has become the "gold standard" for the treatment of symptomatic uncomplicated bile stone disease. Reduced hospitalization time should help reduce cost incurred due to the video surgery material.

Acute Disease↗

[Value of appendectomy by celioscopy: apropos of a series of 73 cases].

The practice of coelioscopic approach in acute appendicitis is still very much debated. A study of the results of 73 patients carried out over two and half years leads one to conclude to the interest of this technique also for the treatment of appendicular peritonitis. Full exploration of the abdominal cavity, easy discovery of ectopic appendix, treatment of associated lesions, extended peritoneal washing, are the observed advantages together with reduced length of hospitalisation and few post-operative complications, in particular parietals problems and obstructions at long term. The experience of the surgeon becomes of prime importance to reduce operating time, frequency of open-surgery converting and complications.

Acute Disease↗

Comparison between lung parenchyma and bronchoalveolar lavage collagenolytic activity.

We have evaluated, in an experimental model of silicosis in guinea pigs, if the presence of collagenolytic activity in bronchoalveolar lavage (BAL) fluid reflects the collagen catabolism in lung parenchyma. We measured simultaneously BAL collagenase activity, using as substrate [3H]type I collagen, and lung collagenolytic activity by the tissue pellet assay. Animals (n = 30) were instilled intratracheally with 50 mg of quartz DQ-12 and sacrificed 15, 30, and 60 days after silica administration. Guinea pigs instilled with saline solution were used as controls. Our results showed that lung parenchymal collagenolytic activity was present in all experimental and normal guinea pigs. There were no statistical differences between silicotic and normal animals at 15 and 30 days. At 60 days, however, a significant decrease in tissue collagenolytic activity was observed in silicotic animals (161 +/- 100 vs. 400 +/- 152 units of collagenase activity; p < 0.001). In contrast, BAL collagenolytic activity was revealed only in 7 of 10 silicotic animals at 15 days and 30 days, and in 4 of 10 at 60 days. Normal guinea pigs did not exhibit BAL collagenase activity. BAL and tissue collagenase activity from each experimental animal were analyzed by straight line regression and no significant relationship was observed (r = 0.082; p = 0.87). This suggests that BAL collagenolytic activity does not reflect lung tissue collagen turnover.

Animals↗

Mortality in Mexican patients with chronic pigeon breeder's lung compared with those with usual interstitial pneumonia.

The clinical course of chronic pigeon breeder's lung (CPBL) is unknown, especially in comparison with usual interstitial pneumonia (UIP). We studied a cohort of 125 consecutive patients with interstitial lung diseases, including 78 patients with CPBL (74 biopsied) and 47 patients with UIP in the lung biopsy. Patients with UIP were divided into 17 without bird exposure (UIP) and 30 with bird exposure (UIP + BE). All patients were treated with corticosteroids and followed for 33 +/- 23 months. The best predictors of mortality (Cox proportional hazards model) were age > 44 yr, with a relative risk (RR) of 2.5 and 95% confidence interval (CI) of 1.4 to 4.7, masculine gender (RR 4.0, CI 2.1 to 7.6), x-ray honeycombing (RR 7.0, CI 3.8 to 12.7), and severity of fibrosis in the lung biopsy (RR 4.8, CI 2.3 to 9.7). Survival in CPBL 5 yr after diagnosis was 0.71 (SEM 0.08) and in UIP was 0.23 (SEM 0.08), with no statistical difference between UIP + BE and UIP. After adjusting for severity of fibrosis and honeycombing, however, the correlation of diagnosis with survival disappeared. In conclusion, mortality in CPBL is considerable, but lower than in UIP. Lung fibrosis and honeycombing seem to be a final common pathway for the ILD. Adjusting for them, the effect of diagnosis in survival is not significant.

Adult↗

O3-induced airway hyperresponsiveness to noncholinergic system and other stimuli.

The effect of O3 exposure (3 ppm, 1 h) on the in vivo and in vitro airway responsiveness, as well as the changes in cell contents in bronchoalveolar lavage (BAL) fluid, were evaluated 16-18 h after O3 exposure in sensitized and nonsensitized male guinea pigs. The sensitization procedure was performed through repeated inhalation of ovalbumin for 3 wk. Increase in pulmonary insufflation pressure produced by the excitatory nonadrenergic noncholinergic (eNANC) system, histamine, and antigen were assessed in in vivo conditions, whereas airway responsiveness to histamine and substance P was evaluated in in vitro conditions by use of tracheal chains with or without epithelium and lung parenchymal strips. We found that O3 exposure 1) increased the neutrophil content in BAL fluids in both sensitized and nonsensitized guinea pigs, 2) caused hyperresponsiveness to eNANC stimulation in nonsensitized guinea pigs (although combination of sensitization and O3 exposure paradoxically abolished the hyperresponsiveness to eNANC stimulation), 3) increased the in vivo bronchoconstrictor responses to histamine and antigen, 4) caused hyperresponsiveness to substance P in nonsensitized tracheae with or without epithelium and in sensitized tracheae with epithelium, 5) did not modify the responsiveness to histamine in tracheae with or without epithelium (and in addition, epithelium removal caused hyperresponsiveness to histamine even in those tracheae exposed to O3), and 6) produced hyperresponsiveness to histamine in lung parenchymal strips either from sensitized or nonsensitized guinea pigs.

Animals↗

Exponential analysis of the lung pressure-volume curve in patients with chronic pigeon-breeder's lung.

Pigeon-breeder's lung (PBL) is extremely common in Mexico City and often progresses to irreversible pulmonary fibrosis. The exponential analysis of the lung pressure-volume (PV) curve (V = A - Be-kp) has been suggested as a method to separate the lung restriction caused by inflammation from that caused by pulmonary fibrosis; a significantly decreased value for the exponential constant, k, suggests a change in the mechanical properties of the functioning lung parenchyma, while a normal value accompanied by restriction suggests subtraction of lung units without a change in the mechanical properties of the functioning units. We measured lung volumes and static PV curves in 29 patients who had persistent lung restriction following a biopsy-proven diagnosis of PBL. Mean values in the 29 subjects were as follows: age, 43 +/- 13 years; TLC, 61 +/- 15 percent of predicted; VC, 46 +/- 19 percent of predicted; and k, 55 +/- 17 percent of predicted. Twenty-four of the 29 patients had values for k that were below the 95 percent confidence level, and five had "normal" values. There was no difference in TLC and VC (percent of predicted) between those with or without a decreased value for k. Four of five patients with a normal value for k improved subsequent to diagnosis, while only one of 21 patients with a decreased k improved. We conclude that increased lung elasticity manifested by a low value for k is common in patients with chronic PBL. These results support the observation of frequent irreversible lung fibrosis in these patients. Measurements of k could prove a good prognostic indicator at the time of initial diagnosis.

Adult↗

Prevalence of high hematocrits in patients with interstitial lung disease in Mexico City.

Erythrocytosis, a known response to chronic hypoxemia, is considered infrequent in interstitial lung diseases. We studied the prevalence of high hematocrit (Hct) values and the relationship between Hct and SaO2 in 79 patients with chronic pigeon breeder's lung (PBL) and 34 with idiopathic pulmonary fibrosis (IPF), all of whom lived in the Mexico City metropolitan area (2,240 m above sea level). Lung biopsy was performed in 31 patients with IPF and 71 with PBL. We analyzed only one simultaneous measurement of Hct and SaO2 per patient (usually the initial measurement) before treatment. No additional cause for anemia or erythrocytosis was detected. Forty-eight percent of the patients with PBL (38/79) and 62 percent of those with IPF (21/34) had high Hct values (greater than 2 SD above mean values for Mexico City); in 14 (12.3 percent) of the 113 patients (nine with PBL and five with IPF), the Hct was above 60 percent. The Hct and SaO2 values displayed a poor correlation for the whole group: Hct = 65.7-0.16(SaO2), r = 0.24, p = 0.012. The correlation between Hct and SaO2 was nonsignificant if patients were separated by diagnosis. For an SaO2 of less than 80 percent, the slope of SaO2 vs Hct was zero. Half of our patients with PBL and IPF had Hct values that were high for the altitude. In most cases, Hct responses fell within the confidence limits reported as normal at high altitudes. We found a poor relationship between Hct and awake SaO2.

Altitude↗

Production of collagenase and tissue inhibitor of metalloproteinases by fibroblasts derived from normal and fibrotic human lungs.

Several experiments have demonstrated low collagenolytic activity during the development of pulmonary fibrosis. In order to determine if fibroblasts play a role in this alteration, procollagenase and tissue inhibitor of metalloproteinases (TIMP) were quantified in fibroblasts derived from 12 human lung specimens (normal = 6, idiopathic pulmonary fibrosis [IPF] = 6). Under basal conditions, three cell strains from normal and three from fibrotic lung specimens did not synthesize collagenase and a similar number of normal and IPF-derived fibroblast strains produced the enzyme. However, the rate of enzyme synthesis among normal and fibrotic collagenase producing fibroblasts exhibited significant differences. Thus, whereas normal fibroblasts produced more than 300 ng/ml, fibrotic lung fibroblasts secreted approximately half of this amount (115 +/- 67 ng/ml). Phorbol myristate acetate (PMA) enhanced collagenase production in all of the 12 lung fibroblast lines tested. In four IPF fibroblasts, PMA increased collagenase secretion close to those of normal stimulated lung fibroblasts; however, a lower induction was observed in cell strains from two fibrotic lung specimens. There was a wide variation in TIMP production both in normal and fibrotic lung fibroblasts, and no statistically significant difference was observed. Under basal conditions, TIMP levels ranged from 329 to 16,911 ng/ml in normal lung cells, and from 377 to 17,557 in fibrotic lung fibroblasts. PMA induced a severalfold increase in all cell lines. These results suggest that there are subpopulations of lung fibroblasts with different potential to produce collagenase and TIMP in vitro, and that the predominance of low collagenase-producing subsets may contribute to the development of fibrosis.

Adult↗

Collagenase-inhibitory activity in deposit and resorption phases of guinea pig carrageenin granuloma.

The levels of collagenase inhibitor, both free and bound to metalloproteinases, were evaluated at 7 days [deposit phase (DP)] and 14 days [resorptive phase (RP)] of evolution of the subcutaneous carrageenin-induced granuloma in the guinea pig. The level of free collagenase inhibitor was considerably higher in the supernatant of DP granulomas (7.95 +/- 1.53 U/mg protein) as compared to that of RP granulomas (2.53 +/- 0.41 U/mg protein). When the samples were heated at acid pH to release the inhibitor from metalloproteinase-inhibitor complexes, free inhibitor was recovered in both phases. However, the units of recovered collagenase inhibitor were several fold higher in all RP granulomas in comparison with DP granulomas (6.88 +/- 2.46 vs 1.5 +/- 0.53). Therefore, DP and RP tissues exhibited similar total amount of tissue inhibitor. By HPLC, collagenase inhibitor activity was localized in a fraction consistent with the size of TIMP. These results suggest a different balance of collagenase and collagenase inhibitor during the evolution of the granuloma; an excess of inhibitor over metalloproteinases appears to predominate during the phase of collagen accumulation contrasting with an inverse situation when the granuloma is healing.

Animals↗

Production of platelet-derived growth factor by human lung cancer.

The production of platelet-derived growth factor (PDGF) was studied in small cell lung carcinoma, lung squamous carcinoma and lung adenocarcinoma cell lines, and in seven human lung tissues obtained from each type of lung cancer. By indirect immunofluorescence, PDGF was detected in all the cell lines. Likewise, five out of seven biopsies derived from patients with adenocarcinoma and squamous carcinoma, and four out of seven specimens with small cell carcinoma displayed a positive pattern for PDGF. In addition, lung carcinoma cell lines expressed both PDGF-A and PDGF-B/sis genes, as judged by Northern blot analysis. Biologically active, serum-free conditioned media obtained from all three cell lines stimulated the incorporation of [3H]thymidine into quiescent BALB/c-3T3 cells. This effect was abolished when IgG-PDGF antiserum was used. These findings suggest that an abnormal expression of PDGF occurs in the three more frequent types of lung cancer, which can play a potential role in neoplastic transformation and uncontrolled cell growth.

Adenocarcinoma↗

Collagenase and collagenase inhibitors in bronchoalveolar lavage fluids.

Collagenase, collagenolytic activity and tissue inhibitor of metalloproteinases were evaluated in bronchoalveolar lavage from 25 patients with hypersensitivity pneumonitis and four control subjects. Patients were followed between two and three years, after which they were classified as "healed," "improved," or "worsened." In control samples, immunoreactive collagenase was not detected. The enzyme was present in four of seven patients who healed, six of ten patients who improved, and four of eight patients who worsened. There was no relationship between the presence or absence of BAL collagenase or its concentration and the evolution of the disease. Latent collagenolytic activity was detected only in 5 of the 14 patients who displayed immunoreactive collagenase. Regarding collagenase inhibitor, TIMP was present in BAL fluid from all patients and normal subjects. Although the highest values were found in two cases who healed or improved, there was not a statistically significant difference among the three groups of patients, neither between patients nor control subjects. These findings suggest that at least in HP, the presence of collagenase, collagenolytic activity, or TIMP in BAL fluid is not associated with the prognosis of the disease.

Adult↗

Adenosine deaminase in the diagnosis of tuberculous pleural effusions. A report of 218 patients and review of the literature.

The activity of adenosine deaminase in the pleural fluid of 218 consecutive patients was studied. According to the etiology of exudative pleural effusions, the patients were divided into the following five groups: (1) tuberculosis; (2) lung cancer; (3) pneumonias; (4) miscellaneous; and (5) idiopathic. Patients with pleural tuberculosis presented significantly higher ADA activity than patients with nontuberculous pleural effusions (p less than 0.0001). The results indicated that in a population with a relatively high prevalence of tuberculosis, the analysis of ADA levels in pleural effusions constitutes a useful marker for the diagnosis which, in addition, can be made quickly and cheaply. Additionally, a comprehensive review of the literature on the role of ADA in the diagnosis of tuberculous pleural effusions is presented.

Adenosine Deaminase↗

Purification of a procollagenase-activator present in medium of cultured guinea pig carrageenin granuloma.

Activation of procollagenase constitutes a crucial event in collagenolytic activity regulation. In this study we have purified by DEAE-cellulose, Ultrogel AcA-44, and zinc chelate sepharose chromatographies, a procollagenase-activator from the culture medium of the guinea pig carrageenin granuloma model. On SDS-PAGE, the activator migrates as a principal band of Mr approximately 44,000. The molecule activates procollagenase from human lung fibroblasts in a concentration dependent manner and an enhancement of collagenase activity of trypsin-treated crude culture medium was observed. A loss of about 50% of its activity occurs after heating. In addition, this activator degrades gelatin and casein. All these data suggest that this procollagenase-activator might be stromelysin. The activator was found in both phases of the granuloma, at 7 days when collagen is actively deposited and an important proportion of the collagenolytic activity remains in latent form; and at 14 days, when this enzymatic activity is fully expressed.

Animals↗