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Biomedical subjects

A Pardo

Publications and source records attributed to A Pardo.

At least 55 records · Page 3Linked to original sources
PubMed1999

Acidic fibroblast growth factor induces an antifibrogenic phenotype in human lung fibroblasts.

Acidic fibroblast growth factor (FGF-1), a prototype member of the heparin-binding growth factor family, influences proliferation, differentiation, and protein synthesis in different cell types. However, its possible role on lung extracellular matrix (ECM) metabolism has not been evaluated. In this study we examined the effects of FGF-1 and FGF-1 plus heparin on type I collagen, collagen-binding stress protein HSP47, interstitial collagenase (matrix metalloproteinase [MMP]-1), gelatinase A, and tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 expression by normal human lung fibroblasts. Heparin was used because it enhances the biologic activities of FGF-1. Fibroblasts were exposed either to 20 ng/ml FGF-1 plus 100 micrograms/ml heparin for 48 h or to FGF-1 or heparin alone. Messenger RNA (mRNA) expression was analyzed by Northern blot. Collagen synthesis was evaluated by digestion of [3H]collagen with bacterial collagenase, MMP-1 by Western blot, and gelatinolytic activities by zymography. Our results show that FGF-1 induced collagenase mRNA expression, which was strongly enhanced when FGF-1 was used with heparin. Likewise, both FGF-1 and FGF-1 plus heparin reduced by 70 to 80% the expression of type I collagen transcript, in part through effect on pro-alpha1(I) collagen mRNA stability. A downregulation of HSP47 gene expression was also observed. Synthesis of collagen and collagenase proteins paralleled gene expression results. FGF-1 activities were abolished with genistein, a tyrosine kinase inhibitor. Neither FGF-1 nor FGF-1 plus heparin affected the expression of TIMP-1, TIMP-2, and gelatinase A. These findings demonstrate that FGF-1, mostly in the presence of heparin, upregulates collagenase and downregulates type I collagen expression that might have a protective role in avoiding collagen accumulation during lung ECM remodeling.

Collagen↗
PubMed1999

Proteinase-antiproteinase imbalance in the pathogenesis of emphysema: the role of metalloproteinases in lung damage.

Pulmonary emphysema refers to a lung disorder characterized by a diffuse destruction of the alveolar walls resulting in enlargement of the distal airspaces. The disease is usually a chronic, progressive, and disabling disorder. The concept of proteinase/antiproteinase imbalance evolved from the identification of patients with alpha 1-antytripsin deficiency, and from the development of experimental emphysematous lesions using different enzymes. For a long time, this concept was seen as an elastase/antielastase imbalance, with the consequent degradation of elastin. Recent evidence, however, suggests that an intricate process of pulmonary remodeling occurs during the development of emphysema, where a complex network of serine proteases and metalloproteinases capable of degrading different extracellular matrix molecules, primarily, but not exclusively fibrillar collagens and elastin, are implicated in the pathogenesis of this disease.

Animals↗
PubMed1999

[Tuberous breast syndrome. Report on a series of 22 operated patients].

The tuberous breast syndrome is a rare unilateral or bilateral breast malformation presenting at the age of mammary development. It requires surgical correction, depending on the severity of the clinical expression, because of its inaesthetic appearance. We report a series of 22 patients (35 breasts) treated and followed up in the plastic and reconstructive surgery department of Rennes over a period of nearly ten years. The average age was 18 +/- 3.2 years (range: 15-26 years old). Long-term results were assessed by the surgical team and the patients on the basis of objective and subjective criteria with an average follow-up of 36 months (12 to 116 months). In our opinion, surgical correction should be proposed after puberty with, whenever possible, section of the basal fibrous ring and glandular plasty via a periareolar incision. The use of mammary implant alone or in combination with breast tissue remodelling must be reserved for hypoplastic cases only.

Adolescent↗
PubMed1998

Myelodysplastic syndrome with erythroid hypoplasia/aplasia: a case report and review of the literature.

Myelodysplastic syndrome (MDS) with erythroid hypoplasia/aplasia has not yet been clearly defined, and in most patients it is mistaken for acquired pure red cell aplasia (PRCA). We report a patient with severe transfusion-dependent anemia (Hb 6.9 g/dl) and reticulocytopenia. WBC and platelet counts were normal. Bone marrow examination showed a marked trilineage dysplasia and a low percentage of erythroid precursors (3%). A diagnosis of MDS (refractory anemia according to FAB classification) with erythroid hypoplasia/aplasia was made. Repeated cytogenetic analysis of bone marrow showed normal karyotypes. Moreover, serial IgM serology and DNA analysis of the patient's sera for B19 parvovirus were negative. Other conditions known to be associated with erythroid aplasia were also absent. The patient failed hematinics and prednisone therapy. He next received r-HuEPO (200 U/kg three times weekly). This form of therapy achieved a rapid and complete erythroid response. He has remained in complete erythroid response after a 7-month period on maintenance therapy of 100 U/kg three times weekly. A review of the literature revealed only 15 well-documented cases of MDS with erythroid hypoplasia/aplasia. All had morphological evidence of myelodysplasia. These patients were predominantly elderly males, all required regular packed red cell transfusions, and had an unfavorable prognosis, mainly because of a high rate of blastic transformation (frequently preceded by a myeloproliferative phase). The mechanism of erythroid hypoplasia in this subgroup of MDS remains uncertain. However, laboratory and clinical data suggest the existence of an intrinsic stem cell defect. None of the patients received hematopoietic growth factors. To our knowledge, our patient is the first case of MDS with erythroid hypoplasia where r-HuEPO was successfully attempted. The description of more cases is necessary to delineate the value of r-HuEPO therapy in this rare variant of MDS.

Adult↗
PubMed1998

Effect of dietary calcium on blood lead concentrations in occupationally exposed and nonexposed workers.

Workers exposed to lead may benefit from a calcium-rich diet, since calcium competes with lead for intestinal absorption. We studied the effect of dietary calcium on blood lead levels. We assessed blood lead levels, dietary intake of calcium, smoking and alcohol consumption, and anthropometric and demographic data in 56 workers exposed to lead and 90 workers without such exposure. Mean intake of dietary calcium was 775 +/- 370 mg/day in the nonexposed workers and 858 +/- 423 mg/day in the exposed workers. Occupational lead exposure explained nearly 90% of the variance in blood lead levels of the entire cohort. Smoking and alcohol intake also showed significant associations with blood lead levels, but their combined effect was less than 2%. When the exposed and nonexposed workers were considered separately, no association was found between blood lead levels and calcium intake. The amount of calcium in the diet does not influence blood lead levels. Further studies are warranted to determine whether dietary calcium influences blood lead levels in exposed and nonexposed workers in other settings and in subjects with lower intakes of calcium.

Adult↗
PubMed1998

Analysis and Transition Probabilities for the Na2 B1Piu --> X1Sigma+g System Using as Excitation the 4727-Å Ar+ Laser Line.

The fluorescence spectrum of Na2 induced by the 4726.87 Å line of an Argon ion laser has been analyzed with special emphasis on determination of accurate relative intensities. This work extends previous observations on Na2 by using this excitation line. We have observed eight fluorescence series for the B1Piu --> X1Sigma+g band system corresponding to the excitation transitions v' = 9, J' = 38 <-- v" = 1, J" = 37; v' = 14, J' = 46 <-- v" = 4, J" = 47; v' = 14, J' = 81 <-- v" = 3, J" = 80; v' = 15, J' = 65 <-- v" = 4, J" = 66; v' = 12, J' = 36 <-- v" = 3, J" = 36; v' = 12, J' = 40 <-- v" = 3, J" = 39 v' = 17, J' = 45 <-- v" = 6, J' = 45 and v' = 18, J' = 63 <-- v" = 6, J" = 63. The seven latter series are reported for the first time. Optically pumped laser transitions obtained in Na2 vapor by using this excitation wavelength have been assigned. The radiative transition probabilities for the observed fluorescence series were calculated using hybrid potential energy curves for the B1Piu and X1Sigma+g states constructed up to last vibrational levels and an ab initio transition dipole moment function. Radiative lifetimes for the rovibrational levels of the upper states pumped by the laser line have also been calculated. The transition probabilities and lifetimes agree with the corresponding observed measurements, usually within the experimental uncertainty. From the rotational satellite structure with DeltaJ' = +/-1 and +/-2 of some bands, for the most intense fluorescence series, collision-induced transition rates and average cross sections have been obtained. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

Gelatinases A and B are up-regulated in rat lungs by subacute hyperoxia: pathogenetic implications.

Subacute hyperoxia may cause basement membrane disruption and subsequent fibrosis. To test the role of extracellular matrix degradation in hyperoxic damage, we analyzed the expression of gelatinases A and B and tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 in rats exposed to 85% O2. Oxygen-exposed rats were studied at 1, 3, 5, and 7 days, and compared with air-breathing rats. Lung mRNAs assayed by Northern and in situ hybridization showed an up-regulation of lung gelatinases A and B from the 3rd day on. Gelatinase A was localized in alveolar macrophages and in interstitial and alveolar epithelial cells. Gelatinase B mRNA and protein were localized in macrophages and bronchiolar and alveolar epithelial cells. Increased gelatinase A and B activities were demonstrated in bronchoalveolar lavage. TIMP-1 and TIMP-2 were constitutively expressed, and only TIMP-1 displayed a moderate increase with hyperoxia. To elucidate transcriptional mechanisms for increased gelatinase B expression after hyperoxia, nuclear transcription factor-kappabeta activation was explored. Oxidative stress significantly increased the lung expression of nuclear transcription factor-kappabeta (p65) protein, and nuclear transcription factor-kappabeta activation and increased levels of gelatinases A and B were found in isolated type II alveolar cells obtained from hyperoxic rats. Conceivably, subacute hyperoxia induces excessive gelatinase activity, which may contribute to lung damage.

Acute Disease↗
PubMed1998

Scaphoid fractures and nonunions: a comparison between panoramic radiography and plain X-rays.

This study describes the diagnostic potential of the panoramic X-ray technique in the evaluation of scaphoid fractures and nonunions. Fifty-eight symptomatic wrists were examined using both plain X-rays and the panoramic procedure. The panoramic images showed in detail the line of the scaphoid fracture and nonunion in detail; they revealed four scaphoid fractures and five nonunions that were not shown clearly with plain X-rays. The panoramic technique is a useful complement to plain X-rays for the investigation of scaphoid fractures and nonunions.

Adolescent↗
PubMed1998

Cell size, cell cycle, and alpha-smooth muscle actin expression by primary human lung fibroblasts.

Primary human lung fibroblasts were separated into small (group I), intermediate (group II), and large (group III) subpopulations by unit gravity sedimentation (1 G). The three subsets retained differences in cell size for up to 15 days of primary culture. Flow cytometric (fluorescence-activated cell sorter) measurements of forward-angle light scatter agreed well with fibroblast volume measured by image analysis and confirmed the utility of forward-angle light scatter for discriminating size subpopulations. Group II fibroblasts accumulated most rapidly by 8 days of culture and also contained the greatest proportion of S and G2/M phase cells as determined by fluorescence-activated cell sorter. Fibroblasts that were immunoreactive with antibodies to alpha-smooth muscle actin (alpha-SMA) were found only in group III. In situ end labeling of fragmented DNA detected apoptotic cells in both groups II and III, but double labeling for in situ end labeling and alpha-SMA revealed apoptotic cells in both the alpha-SMA-positive and -negative populations. These results demonstrate that primary human lung fibroblasts behave as predicted by classic models of cell cycle progression and differentiation. However, they do not support the hypothesis that the expression of alpha-actin is related to apoptosis. We also describe a simple and reproducible method for the high-yield isolation of human lung fibroblast subsets of differing proliferative potential and phenotype.

Actins↗
PubMed1998

Alveolar epithelial cell death adjacent to underlying myofibroblasts in advanced fibrotic human lung.

Earlier work from this laboratory showed that abnormal fibroblast phenotypes isolated from fibrotic human lung produce factor(s) capable of inducing apoptosis and necrosis of alveolar epithelial cells in vitro [B. D. Uhal, I. Joshi, A. True, S. Mundle, A. Raza, A. Pardo, and M. Selman. Am. J. Physiol. 269 (Lung Cell. Mol. Physiol. 13): L819-L828, 1995]. To determine whether epithelial cell death is associated with proximity to abnormal fibroblasts in vivo, the spatial distribution of epithelial cell loss, DNA fragmentation, and myofibroblasts was examined in the same tissue specimens used previously for fibroblast isolation. Paraffin sections of normal and fibrotic human lung were subjected to in situ end labeling (ISEL) of fragmented DNA and simultaneous immunolabeling of alpha-smooth muscle actin (alpha-SMA); replicate samples were subjected to electron microscopy and detection of collagens by the picrosirius red technique. Normal human lung exhibited very little labeling except for positive alpha-SMA immunoreactivity of smooth muscle surrounding bronchi and vessels. In contrast, fibrotic human lung exhibited moderate to heavy ISEL of interstitial, cuboidal epithelial, and free alveolar cells. ISEL of the alveolar epithelium was not distributed uniformly but was most intense immediately adjacent to underlying foci of alpha-SMA-positive fibroblast-like interstitial cells. Both electron microscopy and picrosirius red confirmed epithelial cell apoptosis, necrosis, and cell loss adjacent to foci of collagen accumulation surrounding fibroblast-like cells. These results demonstrate that the cuboidal epithelium of the fibrotic lung contains dying as well as proliferating cells and support the hypothesis that alveolar epithelial cell death is induced by abnormal lung fibroblasts in vivo as it is in vitro.

Apoptosis↗
PubMed1997

Spontaneous bacterial peritonitis in patients with cirrhosis undergoing selective intestinal decontamination. A retrospective study of 229 spontaneous bacterial peritonitis episodes.

BACKGROUND/AIMS: Selective intestinal decontamination with norfloxacin is widely used to prevent spontaneous bacterial infections in cirrhosis. The study was performed to compare the spontaneous bacterial peritonitis occurring in patients with and without prophylactic norfloxacin. METHODS: Two hundred and twenty-nine consecutive episodes of spontaneous bacterial peritonitis, (193 in patients without (Group A) and 36 in patients with norfloxacin prophylaxis (Group B)), were retrospectively analyzed. In 100 episodes (86 and 14, respectively), the responsible organism was isolated in ascitic fluid. RESULTS: Clinical and laboratory data at diagnosis were comparable in both groups. There were marked differences (p < 0.001) between group A and B in the frequency of peritonitis caused by gram-negative (67.4% vs. 14.3%) and gram-positive (30.2% vs. 78.6%) bacteria. There were three polymicrobial episodes. Bacteria resistant to cefotaxime and gram-negative bacilli resistant to quinolones were isolated in ascitic fluid in nine (seven in Group A and two in Group B) and three episodes (all in Group A), respectively. No differences in the course of infection and patient survival were observed between groups. CONCLUSIONS: Spontaneous bacterial peritonitis in patients with and without prophylaxis with norfloxacin are not different in clinical features, response to treatment and prognosis. Spontaneous bacterial peritonitis caused by gram-negative organisms resistant to quinolones is extremely uncommon in patients with cirrhosis receiving prophylactic norfloxacin.

Adult↗
PubMed1997

Diuretic requirements after therapeutic paracentesis in non-azotemic patients with cirrhosis. A randomized double-blind trial of spironolactone versus placebo.

BACKGROUND/AIMS: Diuretic requirements after mobilization of ascites by paracentesis have never been assessed in cirrhosis. It is also unknown whether diuretics increase the incidence of postparacentesis circulatory dysfunction. The aim of this study was to investigate these features and to assess whether measurement of plasma renin activity and aldosterone prior to paracentesis predicts diuretic response after this procedure. METHODS: Thirty-six patients with non-azotemic cirrhosis and ascites treated by total paracentesis plus i.v. albumin were randomly assigned to receive placebo (n=17) or spironolactone 225 mg/day (n=19) immediately after paracentesis and followed-up for 4 weeks. RESULTS: Five patients (three in the placebo and two in the spironolactone group) abandoned the treatment prior to ascites recurrence or the end of the study due to complications or lack of compliance. The analysis was performed in the remaining 31 patients. Ascites recurrence was more common in the placebo group (13 cases, 93%) than in the spironolactone group (3 cases, 18%) (p<0.0001) and occurred within the first 2 weeks of follow-up in more than 50% of patients. Patients developing ascites in the spironolactone group had higher levels of renin (14.1, 20.6, 32.4 ng/ml per h) and aldosterone (120, 149, 288 ng/dl) than those who did not develop ascites (renin: 2.0+/-2.1 ng/ml per h; range 0.1-6.8; aldosterone: 43+/-38 ng/dl; range 4-116). Three patients in the placebo group and two in the spironolactone group developed postparacentesis circulatory dysfunction (defined as an increase in renin at the third day after paracentesis greater than 50% over baseline levels up to a value higher than 4 ng/ml per h). CONCLUSIONS: Patients with cirrhosis treated by paracentesis should receive diuretics immediately after this procedure to prevent early recurrence of ascites. The administration of 225 mg/day of spironolactone is a good empiric treatment for non-azotemic patients with cirrhosis, because it is effective in most cases and does not increase the incidence of postparacentesis circulatory dysfunction. The determination of plasma levels of renin or aldosterone prior to paracentesis predicts the efficacy of spironolactone in the prevention of ascites recurrence.

Aldosterone↗
PubMed1997

Lung alveolar epithelial cells synthesize interstitial collagenase and gelatinases A and B in vitro.

Type II pneumocytes are multifunctional alveolar epithelial cells that play a major role in the maintenance of lung structure and function. Recent evidence supports that these cells can synthesize a variety of extracellular matrix components in vitro, suggesting an active participation in connective tissue remodeling. However, their possible role in extracellular matrix degradation is unknown. In this study the production of matrix metalloproteinases (MMPs) was examined in primary cultures of rat alveolar type II pneumocytes after 2 and 7 days in culture. Under basal conditions, at both periods type II cells expressed interstitial collagenase mRNA. The immunoreactive protein was detected both in the cells and in conditioned media, and collagenolytic activity was revealed after trypsin activation. Gelatinolytic activity was detected by zymography showing a relative molecular mass of approximately 72 and 92 kDa (gelatinases A and B). Phorbol treatment increased collagenase and gelatinase activities. In addition, three alveolar epithelial cell lines were analysed for MMP production: MLE-12 (mice), L2 (rat), and A549 (human). The cell lines A549 and MLE-12 revealed collagenase and gelatinase A and B activities whereas the L2 cell line only exhibited gelatinase A activity, even after PMA induction. These findings demonstrate that alveolar epithelial cells synthesize in vitro several MMPs that confer on them the ability to degrade extracellular matrix and basement membrane components, a capacity of considerable importance for the remodeling of the stromal/epithelial interface.

Animals↗
PubMed1997

Upregulation of acidic fibroblast growth factor during development of experimental lung fibrosis.

Fibroblast proliferation and extracellular matrix accumulation are crucial in the pathogenesis of lung fibrosis. Fibroblast growth factor (FGF)-1 participates in both processes, but its role in lung fibrogenesis has not been evaluated. We analyzed the expression of FGF-1 and of FGF receptor (FGFR) in a model of lung fibrosis induced in rats with paraquat plus hyperoxia. Experimental and control animals were killed at 48 h and 2, 4, and 8 wk, and the lungs were studied by in situ hybridization, immunohistochemistry, and Northern blot. In normal lungs, scattered macrophages contained FGF-1. In contrast, at all times examined, the injured lungs exhibited FGF-1 transcript and the immunoreactive protein, mainly in alveolar epithelial cells and macrophages. In advanced fibrotic lesions, fibroblasts also appeared stained. Northern blot corroborated the upregulation of FGF-1 mRNA. FGFR was not observed in normal lungs, whereas it was strongly increased in the damaged lungs and was virtually immunolocalized in the same cell types as the corresponding ligand. These findings suggest that FGF-1 and FGFR are actively synthesized during the development of pulmonary fibrosis.

Animals↗
PubMed1996

EBV-positive non-Hodgkin's lymphoma developing after phenytoin therapy.

We report the first case of Epstein Barr virus (EBV) positive non-Hodgkin's lymphoma occurring 20 years after continuous phenytoin therapy for idiopathic epilepsy. This malignant lymphoproliferative disease was preceded by an phenytoin-associated benign reactive lymphadenopathy. Serological findings suggested a chronic active EBV infection. Immunohistochemistry showed that neoplastic cells expressed B antigens (CD20, lambda) and the bcl-2 protein. The presence of EBV-encoded latent membrane protein 1 (LMP 1) was also expressed on neoplastic cells. Cytotoxic chemotherapy (CHOP) reversed the non-Hodgkin's lymphoma.

Anticonvulsants↗
PubMed1996

Tobacco smoke-induced lung emphysema in guinea pigs is associated with increased interstitial collagenase.

We examined the expression of interstitial collagenase and its enzymatic activity in lung damage induced by tobacco smoke. Guinea pigs were exposed to the smoke of 20 cigarettes per day from 1-8 wk. Age-matched guinea pigs were used as controls. At 6 and 8 wk of smoke exposure, lungs exhibited interstitial and peribronchiolar inflammation and moderate emphysematous changes. In situ hybridization of injured lungs revealed patchy expression of collagenase mRNA mainly in macrophages but also in alveolar epithelial and interstitial cells. Immunoreactive protein was detected in alveolar macrophages and in the alveolar walls and interstitium. Collagenolytic activity increased beginning in the 4th wk of exposure (0.7 +/- 0.43 micrograms collagen degraded/mg collagen incubated relative to 0.23 +/- 0.14 in controls; P < 0.05). At 6 and 8 wk, values were 0.85 +/- 0.34 and 0.98 +/- 0.33 compared with 0.25 +/- 0.11 and 0.26 +/- 13 in controls (P < 0.005 and 0.001). Collagen concentration decreased from 50.7 +/- 8.5 mg/g dry wt in control lungs to 40.2 +/- 5.0 and 42.9 +/- 6.0 at 6 and 8 wk of exposure, respectively (P < 0.05). These results strongly suggest that increased interstitial collagen degradation plays a role in the development of lung emphysema.

Animals↗