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Biomedical subjects

M F Lopes

Publications and source records attributed to M F Lopes.

At least 19 recordsLinked to original sources
PubMed2006

Esophageal replacement in rat using porcine intestinal submucosa as a patch or a tube-shaped graft.

This study compares the efficacy of porcine intestinal submucosa (SIS) patch graft versus SIS-tube graft in esophageal replacement, using a novel esophageal regeneration model. Clinical function, as well as macroscopic and microscopic morphology were evaluated in both SIS-treated groups. We performed semi-circumferential esophageal excision followed by repair of the defect using either a SIS-patch graft (group I) or segmental esophageal excision followed by a SIS-tube interposition graft (group II) in rats. The 28-day survival rate was significantly different between the SIS-treated groups (100% in group I vs. 0% in group II). Unlike the rats in group II, which died within the first postoperative month due to esophageal dysfunction, all surviving animals in group I resumed a normal solid diet within a few days after surgery, without signs of esophageal dysfunction and gained weight. Barium swallow studies showed no evidence of fistula, significant stenosis or diverticula. No hematological or serum biochemistry abnormalities were found. By day 150 the SIS patch was replaced by esophageal-derived tissues. In the rat model, a patch graft technique using SIS appeared to induce esophageal regrowth and provided an initial and long-term satisfactory function, while a tube-shaped graft technique using SIS was unsuccessful.

Animals↗
PubMed2003

Endoscopic obliteration of a recurrent tracheoesophageal fistula with enbucrilate and polidocanol in a child.

We present a difficult case of a recurrent tracheoesophageal fistula following primary surgical repair of esophageal atresia. After four unsuccessful attempts to close the fistula, which included three thoracotomies and one endoscopic obliteration using fibrin glue, successful recurrent tracheoesophageal fistula closure was attained with the endoscopic application of enbucrilate (Histoacrylate) combined with polidocanol. Enbucrilate was applied into the lumen of the fistula by bronchoscopy, and polidocanol (Sclerovein) was injected into the esophageal submucosa around the fistula by esophagoscopy. Three years after this treatment, the fistula remains apparently closed.

Bronchoscopy↗
PubMed2001

Fas ligand triggers pulmonary silicosis.

We investigated the role of Fas ligand in murine silicosis. Wild-type mice instilled with silica developed severe pulmonary inflammation, with local production of tumor necrosis factor (TNF)-alpha, and interstitial neutrophil and macrophage infiltration in the lungs. Strikingly, Fas ligand-deficient generalized lymphoproliferative disease mutant (gld) mice did not develop silicosis. The gld mice had markedly reduced neutrophil extravasation into bronchoalveolar space, and did not show increased TNF-alpha production, nor pulmonary inflammation. Bone marrow chimeras and local adoptive transfer demonstrated that wild-type, but not Fas ligand-deficient lung macrophages recruit neutrophils and initiate silicosis. Silica induced Fas ligand expression in lung macrophages in vitro and in vivo, and promoted Fas ligand-dependent macrophage apoptosis. Administration of neutralizing anti-Fas ligand antibody in vivo blocked induction of silicosis. Thus, Fas ligand plays a central role in induction of pulmonary silicosis.

Adoptive Transfer↗
PubMed2001

Intracellular protozoan parasites and apoptosis: diverse strategies to modulate parasite-host interactions.

Programmed cell death (apoptosis) is an important regulator of the host's response during infection with a variety of intracellular protozoan parasites. Parasitic pathogens have evolved diverse strategies to induce or inhibit host-cell apoptosis, thereby modulating the host's immune response, aiding dissemination within the host or facilitating intracellular survival. Here, we review the molecular and cell-biological mechanisms of the pathogen-induced modulation of host-cell apoptosis and its effects on the parasite-host interaction and the pathogenesis of parasitic diseases. We also discuss the previously unrecognized phenomenon of apoptotic cell death in (unicellular) protozoan parasites and its potential implications.

Animals↗
PubMed2000

Uptake of apoptotic cells drives the growth of a pathogenic trypanosome in macrophages.

After apoptosis, phagocytes prevent inflammation and tissue damage by the uptake and removal of dead cells. In addition, apoptotic cells evoke an anti-inflammatory response through macrophages. We have previously shown that there is intense lymphocyte apoptosis in an experimental model of Chagas' disease, a debilitating cardiac illness caused by the protozoan Trypanosoma cruzi. Here we show that the interaction of apoptotic, but not necrotic T lymphocytes with macrophages infected with T. cruzi fuels parasite growth in a manner dependent on prostaglandins, transforming growth factor-beta (TGF-beta) and polyamine biosynthesis. We show that the vitronectin receptor is critical, in both apoptotic-cell cytoadherence and the induction of prostaglandin E2/TGF-beta release and ornithine decarboxylase activity in macrophages. A single injection of apoptotic cells in infected mice increases parasitaemia, whereas treatment with cyclooxygenase inhibitors almost completely ablates it in vivo. These results suggest that continual lymphocyte apoptosis and phagocytosis of apoptotic cells by macrophages have a role in parasite persistence in the host, and that cyclooxygenase inhibitors have potential therapeutic application in the control of parasite replication and spread in Chagas' disease.

Amino Acid Chloromethyl Ketones↗
PubMed2000

Fetal intestinal graft is the best source for intestinal transplantation.

Adult intestinal allografts have demonstrated high immunogenicity in human transplantation, making the search for new and more favorable grafts an actual problem. Accepting that fetal and newborn immune systems are relatively immature, their intestines could be ideal sources for organ donation. The purpose of this study was to compare the immunogenicity of fetal, newborn, and adult intestine for selection of the least antigenic. Using a bidirectional rat model for immunologic responses, 116 small-bowel transplantations were done: 36 fetal, 40 newborn, and 40 adult grafts. Two histocompatibility barriers and different immunosuppression regimes were used. For fetal and newborn intestines, free grafts into the omentum of adult recipients were done; for adult intestines, accessory grafts in adult recipients of the same age, using vascular anastomoses. The diagnosis of graft rejection and graft-versus-host disease (GVHD) was based on histology of hematoxylin and eosin-stained biopsies from target organs. Recipients of fetal and newborn grafts did not show signs of GVHD, while 12% of the adult group did (P < 0.05). Rejection was less severe in fetal and adult (P > 0.05) than in newborn (P < 0.05) intestinal transplantation. Treatment with 10 mg/kg per day cyclosporine prevented rejection in 70% of fetal and 75% of adult grafts, while all newborn grafts were rejected. Under no immunosuppression, or with low doses of cyclosporine (2 mg/kg per day), all groups showed histologic signs of rejection in almost all cases, the fetal intestine being the least affected. Concerning histocompatibility barriers, grafts were usually less damaged in the weaker transplantation subgroups. Our data indicate that fetal intestine is the least immunogenic of the three grafts studied, suggesting that it will be the most suitable tissue for organ donation.

Age Factors↗
PubMed1999

Increased susceptibility of Fas ligand-deficient gld mice to Trypanosoma cruzi infection due to a Th2-biased host immune response.

Infection of BALB/c mice with Trypanosoma cruzi resulted in up-regulated expression of Fas and Fas ligand (FasL) mRNA by splenic CD4+ T cells, activation-induced CD4+ T cell death (AICD), and in Fas: FasL-mediated cytotoxicity. When CD4+ T cells from infected mice were co-cultured with T. cruzi-infected macrophages, onset of AICD exacerbated parasite replication. CD4+ T cells from T. cruzi-infected FasL-deficient BALB gld/gld mice had no detectable AICD in vitro and their activation with anti-TCR did not exacerbate T. cruzi replication in macrophages. However, infection of BALB gld/gld mice with T. cruzi resulted in higher and more prolonged parasitemia, compared to wild-type mice. Secretion of Th2 cytokines IL-10 and IL-4 by CD4+ T cells from infected gld mice was markedly increased, compared to controls. In addition, in vivo injection of anti-IL-4 mAb, but not of an isotype control mAb, reduced parasitemia in both gld and wild-type mice. These results indicate that, besides controlling CD4+ T cell AICD and parasite replication in vitro, an intact Fas: FasL pathway also controls the host cytokine response to T. cruzi infection in vivo, being required to prevent an exacerbated Th2-type immune response to the parasite.

Animals↗
PubMed1999

Registered designation of origin areas of fermented food products defined by microbial phenotypes and artificial neural networks.

Cheese produced from raw ewes' milk and chouriço, a Portuguese dry fermented sausage, are still produced in a traditional way in certain regions of Portugal by relying on colonization by microbial populations associated with the raw materials, equipment, and local environments. For the purpose of describing the product origins and types of these fermented foods, metabolic phenotypes can be used as descriptors of the product as well as to determine the presence of compounds with organoleptic value. The application of artificial neural networks to the metabolic profiles of bacterial isolates was assayed and allowed the separation of products from different regions. This method could then be used for the Registered Designation of Origin certification process of food products. Therefore, besides test panel results for these traditionally produced food products, another tool for validating products for the marketplace is available to the producers. The method can be improved for the detection of counterfeit products.

Animals↗
PubMed1998

Activation-induced T cell death exacerbates Trypanosoma cruzi replication in macrophages cocultured with CD4+ T lymphocytes from infected hosts.

Activation-induced cell death (AICD) of CD4+ T lymphocytes was described in infection with Trypanosoma cruzi, but a role for AICD in modulating parasite spread in host cells has not been investigated. In this study, replication of T. cruzi in vitro in murine macrophage (Mphi) monolayers was investigated. Long term (5 to 13 day) replication of infective (trypomastigote) T. cruzi forms was blocked by supernatants from activated (anti-TCR) CD4+ T cells of infected mice or by rIFN-gamma. However, when CD4+ T cells from infected mice were cocultured with Mphi and activated by anti-TCR, marked exacerbation of trypomastigote growth in Mphi ensued. The deleterious effect required contact between T cells and infected Mphi. Both anti-Fas and TCR activation killed a proportion of CD4+ T cells. Ly-6 activation did not induce AICD and did not exacerbate parasite growth. However, Fas-mediated killing of T cells before Ly-6 activation led to exacerbated parasite growth. Although a minor population, Fas-susceptible cells were the major source of IFN-gamma production by activated T cells. Addition of a neutralizing anti-Fas ligand antibody blocked 50 to 60% of CD4+ T cell AICD and reduced trypomastigote growth in T/Mphi cocultures stimulated by anti-TCR. The results demonstrate that in CD4+ T cells from infected mice, the onset of AICD selectively ablates IFN-gamma production and up-regulates parasite replication in Mphi in vitro. These findings suggest a deleterious role for AICD in T. cruzi infection.

Animals↗
PubMed1998

Techniques of intestinal transplantation in rat.

Two surgical models of intestinal transplantation in the rat are described. One is the implantation of fetal and newborn intestine as free grafts into the omentum of adult recipients, the other the adult intestine transplantation as an accessory graft using vascular anastomoses. A hundred and sixteen small-bowel transplantations were done; 36 of which were fetal intestine (group I), 40 of newborn intestine (group II), and 40 of adult intestine (group III). In the fetal and newborn intestinal transplantation, we emphasize the practices that allowed us to avoid ischemic and traumatic injury to the graft. In the adult intestine transplantation with vascular anastomoses, we heighten the modifications in the surgical technique that made the operation easier and the strategies used to prevent hypothermia and hypovolemic shock. Once experienced with the two chosen surgical techniques, transplantation using an avascular segment became much easier and quicker than transplantation with vascular anastomoses.

Anastomosis, Surgical↗
PubMed1998

[Bladder rupture in a child with Ehlers-Danlos syndrome phenotype].

We report a case of "spontaneous" bladder rupture in a child with type IV Ehlers-Danlos Syndrome phenotype. The clinical presentation was unusual with abdominal pain, urinary retention and recurrent rectal prolapse. We could not find other similar cases in the literature. We to the possibility of "spontaneous" rupture occurring in this type of patients.

Child, Preschool↗
PubMed1996

Trypanosoma cruzi-induced immunosuppression: selective triggering of CD4+ T-cell death by the T-cell receptor-CD3 pathway and not by the CD69 or Ly-6 activation pathway.

In a model of experimental Chagas' disease induced with metacyclic forms of Trypanosoma cruzi, CD4+ but not CD8+ T cells undergo T-cell receptor (TCR)-CD3-mediated activation-induced cell death (AICD) in vitro. CD4+ T cells from T. cruzi-infected mice also developed unresponsiveness in proliferative responses to TCR-CD3-mediated stimulation. A linear correlation was found between extent of proliferative unresponsiveness and loss of CD4+ T-cell viability. CD4+ T-cell activation through the CD69 or Ly-6 A/E pathway, on the other hand, did not result in proliferative unresponsiveness compared with controls. Lack of suppression in proliferation assays correlated with lack of AICD by cells stimulated through the CD69 or Ly-6 A/E pathway. Concomitant stimulation through CD69, however, did not rescue CD4+ T cells from CD3-induced death. Flow cytometry study of cells stimulated in vitro showed no defect in interleukin-2 receptor expression by CD4+ T cells from infected donors, which escaped TCR-mediated AICD. In vivo injection of anti-CD3 into acutely infected mice, but not into control mice, led to splenocyte DNA fragmentation and failed to increase splenic CD4+ T-cell numbers. These results show that TCR-CD3-mediated AICD is involved in CD4+ T-cell unresponsiveness in vitro following infection with T. cruzi. In addition, successful activation of these cells through the CD69 and Ly-6 pathways is due to differences in the inability of these stimuli to trigger AICD. Since TCR-CD3-mediated AICD can be induced in vivo in infected mice, these findings may be relevant for the onset of immunological disturbances in the host.

Animals↗
PubMed1995

Activation-induced CD4+ T cell death by apoptosis in experimental Chagas' disease.

Infection of mice with Trypanosoma cruzi, the causative protozoan agent of human Chagas' disease, leads to immunosuppression of the T cell compartment and to chronic cardiac inflammation which resembles the human infection. Recently, reinduction of programmed cell death by apoptosis in mature T cells has been demonstrated. It has been suggested that mature T cell apoptosis could play a role in immunosuppression caused by virus infection. In this report, we have investigated the occurrence of mature T cell apoptosis in murine experimental Chagas' disease. Infection with T. cruzi metacyclic forms led to a relative accumulation of CD8 T cells over CD4 T cells in the spleens of infected mice. Splenic T cells from T. cruzi-infected donors, but not from control littermates, died in vitro upon stimulation with T cell mitogens Con A and anti-TCR-alpha beta mAb in a dose-dependent fashion. DNA fragmentation into nucleosome-sized bands was detected in the supernatants of CD4+ T cells from infected origin, after stimulation with the T cell mitogen Con A. Upon in vitro stimulation with either anti-TCR-alpha beta or Con A, CD4+ T cells were susceptible to elimination, whereas CD8+ T cells were not. Splenic T cells from infected donors were markedly unresponsive to anti-TCR mAb in proliferative assays and underwent apoptosis in vitro, as assessed by electron microscopy. Apoptosis also occurred in vivo in the course of acute infection, as seen by DNA fragmentation in freshly explanted splenic cells and purified T cell subsets. The data indicate that activation-induced CD4+ T cell death by apoptosis is a prominent feature of experimental infection with T. cruzi, and could play a role in immunosuppression and parasite persistence in infected hosts.

Animals↗
PubMed1995

Trypanosoma cruzi: both chemically induced and triatomine-derived metacyclic trypomastigotes cause the same immunological disturbances in the infected mammalian host.

Infection of BALB/c mice with chemically induced metacyclic forms of Trypanosoma cruzi clone Dm28c led to characteristic changes of experimental Chagas' disease, with protracted but marked parasitemia, intense splenomegaly, and splenic T cell hyporeactivity to TcR;CD3-dependent stimulation. Infection of BALB/c mice with either chemically induced or triatomine-derived Dm28c metacyclic forms led to comparable parasitemias, a synchronous increase in the number of splenic large lymphocytes, and a similar reduction in T cell responsivity to immobile anti-CD3 antibody. A marked and selective reduction in the level of CD8 expression per cell was also seen in mice infected with either form of metacyclic parasites. Large inflammatory mononuclear cell infiltrates were present in the hearts of mice infected with either chemically induced or insect vector-derived metacyclic forms, at both acute and chronic stage, with predominance of CD8 over CD4 T cells in the lesions, in both cases. These results indicate that infection with chemically induced metacyclic forms of T. cruzi can be a useful model of Chagas' disease, resembling infection caused by the insect vector.

Animals↗
PubMed1995

Programmed T-cell death in experimental chagas disease.

In mature T cells, programmed cell death is thought to serve a regulatory function by limiting both the duration and amplitude of immune responses. Programmed cell death might also be involved in immuno-pathogenesis of certain infectious diseases: recent evidence suggests that programmed T-cell death plays an important role in immune suppression during viral infections. In this article, George DosReis, Maria Evangelina Fonseca and Marcela Lopes review their findings on programmed T-cell death in experimental infection induced by the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease. They also discuss the differential behavior of CD4(+) and CD8(+) T-cell subsets regarding programmed cell death, and same possible pathogenic aspects of host-parasite interaction, where abnormal or exaggerated programmed T-cell death could be involved.

Journal Article↗
PubMed1995

Partial characterization of the cohemolytic factor produced by Streptococcus uberis and comparison with the CAMP-factor.

Exosubstances (cohemolysins) produced by Streptococcus agalactiae (CAMP-factor) and Streptococcus uberis (Uberis-factor) showing hemolytic synergism with beta-lysin produced by Staphylococcus aureus were compared. Cohemolytic activity was evaluated in the supernatants of bacterial cultures, before and after ammonium sulfate precipitation. Sheep erythrocytes sensitized with beta-lysin were used as substrate. The assays were performed in microtiter plates and results were expressed as cohemolytic units/ml. Maximum cohemolytic activity was detected, respectively, after 8 h and 14 h of growth in Columbia broth in S. uberis and S. agalactiae cultures. Cohemolytic activities of both microorganisms showed similarities when submitted to various physical and chemical treatments. They were significantly decreased by heating at 60 degrees C and 100 degrees C, or in presence of trypsin, and were abolished in the presence of Tween 20. Activities were found to be stable in crude supernatants and concentrated preparations maintained at -20 degrees C for 3 months. Differences were related to levels of activity and kinetics of detection during the growth cycle. The results indicate the proteic nature, at least in part, of the Uberis factor. Analysis by PAGE in the presence or absence of SDS allowed us to correlate Uberis activity with a protein band with apparent molecular mass of 42 kDa, while CAMP activity was associated with a protein band of 27 kDa.

Bacterial Proteins↗