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Biomedical subjects

M Salcedo

Publications and source records attributed to M Salcedo.

At least 73 records · Page 4Linked to original sources
PubMed1996

Triggering of natural killer cells by the costimulatory molecule CD80 (B7-1)

NK cell-mediated cytotoxicity is influenced by triggering as well as inhibitory signals. The identification of inhibitory signals provided by MHC class I molecules has recently attracted significant attention. Much less is known about putative triggering signals. Using purified populations of mouse NK cells, we demonstrate that the CD80 (B7-1) gene product functions as a triggering signal for NK cell-mediated cytotoxicity. The strength of this response is such that it overrides the protection mediated by MHC class I molecules. Triggering of mouse NK cells by B7-1 occurred even in the absence of CD28 and could not be blocked by either anti-CD28 or anti-CTLA-4 antibodies. NK cells may thus, at least in part, use receptors other than CD28 and CTLA-4 in their interaction with B7-1. Furthermore, we demonstrate that bone marrow-derived macrophages and dendritic cells are highly susceptible to lysis by autologous NK cells.

Animals↗
PubMed1996

[Orthotopic hepatic transplant in chronic hepatopathy of alcoholic origin].

Liver transplantation for alcoholic cirrhosis remains controversial at some transplantation centers. We compared resource utilization and outcome in alcoholic and non-alcoholic cirrhotic patients undergoing liver transplantation. From April 1990 to November 1994, 60 patients received orthotopic liver transplants for end-stage alcoholic liver disease, and 119 transplants were performed in 103 patients for non-alcoholic liver disease. No significant differences were noted in resource utilization of the variables examined. The outcome of liver transplantation (early graft function, frequency of sepsis, incidence of rejection, renal function, arterial hypertension...) was equivalent or better in alcoholic patients. Postoperative mortality was higher in non-alcoholic population (25.2% vs 16.7%). One-year and three year actuarial survival was not significantly different, but it was higher in the alcoholic group (77% vs 67% and 74% vs 64% respectively). The recurrence rate of alcohol in take has been 9.09%, with most patients drinking only socially. We conclude that liver transplantation for end-stage alcohol-related cirrhosis provides excellent results and resource utilization appears to be equivalent to that for patients undergoing transplantation for non-alcohol-related cirrhosis.

Female↗
PubMed1996

[Treatment with interferon alfa-2b in patients with chronic hepatitis caused by hepatitis C virus: predictive factors for the response, relapse and early development to cirrhosis after treatment].

UNLABELLED: The treatment of chronic hepatitis C is interferon (IFN). Diverse predictive factors influence a complete response. The aim of this study was to determine the response to IFN-alpha therapy and factors that may predict a sustained response before and after the first month of treatment. Likewise, it evaluates the relapse and liver cirrhosis evolution after therapy. PATIENTS AND METHODS: We have treated 155 consecutively patients with chronic hepatitis C. Nine left therapy because of severe side effects. We studied the patients who had had persistently elevated serum aminotransferase concentrations, HBsAg negative, HIV negative and antiHCV positive with polymerase chain reaction confirmation, and without any other liver disease. The schedule of IFN-alpha 2b therapy was 5 MU three times per week for 3 months, and later, 3 MU three times per week for 6 more months. There were two groups of response: A) Complete response, if serum aminotransferase levels were normal and RNA-HCV negative, B) No response, if it didn't meet these conditions. The sustained response was complete response during follow-up. The relapse described as aminotransferase increase after suppression therapy with or without positive RNA-HCV, or positive RNA-HCV only. RESULTS: A complete response was obtained in 34.9%. Ten variables were statistically significant (p < 0.05) on univariate analysis: weight, corporal surface, dosage IFN/m2, bilirubin and total protein pretreatment; polymorphonuclears/mononuclears cells, AST, ALT, AST/ALT, and gamma GT in the first therapy's month. In multivariate analysis, serum AST levels < 40 U/l (odds ratio 0.15, 95% CI 0.04-0.52), and AST/ALT ratio > 0.75 (odds ratio 3.05, 95% CI 1.04-8.9) in the first month, were correlated independently with complete response. Incidence of relapse was 47% of responders, with mean appearance period a of 2.7 +/- 2.1 months. Therefore, a sustained response was obtained in 27 patients (18.5%). Seventeen of 115 patients (14.6%) without cirrhosis initially, developed liver cirrhosis after a second biopsy. Two variables were statistically significant in multiple regression analysis: RNA-HCV positive after treatment (odds ratio 2.99, 95% CI 0.9-2.99), and platelet count < 180,000/mm3 before therapy (odds ratio 17.7, 95% CI 3.7-83.2) were correlated independently with cirrhosis development. CONCLUSIONS: A 9 months course of IFN therapy is effective in a third of patients, but almost half of them have relapsed within 6 months after treatment's suppression. The AST levels and AST/ALT ratio in the first of month therapy were correlated independently with complete response. Liver cirrhosis appears in a small percentage. Platelet count before therapy and RNA-HCV positive at the end treatment, were predictor variables of this evolution.

Adult↗
PubMed1995

Natural killer cell interaction with murine allogeneic MHC class I molecules.

Class I molecules of the MHC affect target cell sensitivity to NK cell repertoire. In the mouse, absence of MHC class I molecules on target cells is associated with an increased susceptibility to NK cell-mediated lysis, while syngeneic class I molecules confer protection. In contrast to the protective role of syngeneic class I molecules, less is known about the interaction between murine NK cells and allogenic class I MHC molecules. In theory, such could either be triggering, inert, or inhibitory. To directly address the role of allogeneic class I in interaction with NK cells of the mouse, a panel of polyclonal allogeneic murine NK cells were exposed to H-2b class I positive or negative target cells, and susceptibility to lysis was assessed. For all effectors studied, regardless of H-2 haplotype or genetic background, a preferential killing of class I-deficient targets was observed. This pattern was observed in vitro with tumor as well as lymphoblast targets, and in vivo in rapid elimination studies of radiolabeled tumor cells. The results demonstrate that protection from murine NK cell-mediated lysis can be conferred by the expression of allogeneic class I molecules. No evidence for a triggering effect caused by the expression of allogeneic class I molecules was observed. The data are discussed in relation to current models on NK cell/MHC class I interactions, alloreactivity mediated by NK cells, and the role of NK cells in allogeneic graft rejection responses.

Animals↗
PubMed1995

Altered MHC class I presented peptide repertoire is not sufficient to induce NK cell mediated F1-hybrid resistance.

Murine NK cells are known to mediate F1-hybrid anti-parental graft rejection responses. This phenomenon has been linked to the MHC, and in particular, to the alpha 1/alpha 2 domains of the MHC class I molecules. Here, we have addressed the role of MHC class I bound peptides in NK cell mediated F1-hybrid anti-parental rejection by studying the resistance of F1-hybrids between B6 and different bm mutant strains to B6-derived RBL-5 lymphoma cell line. Tumor development occurred at a similar frequency in all combinations of (B6 x bm)F1 mice and control B6 mice. These results suggest that absence of a specific MHC class I presented peptide repertoire on grafted cells is not sufficient to induce NK cell mediated F1-hybrid anti-parental rejection responses.

Animals↗
PubMed1995

[Tracheoesophageal fistula secondary to endoscopic sclerotherapy of esophageal varices].

Over the past 15 years, endoscopic variceal sclerotherapy (EVS) has become the main therapy for patients with bleeding esophageal varices. EVS has the advantage of a low associated mortality and morbidity, but may lead to serious complications. We report a case of esophagotracheal fistula complicating sclerotherapy that resolved with nonsurgical management.

Aged↗
PubMed1995

[Hydrogen peroxide-induced lesions in the digestive tract. Apropos 4 cases].

Gastrointestinal injury caused by caustic products a are relatively infrequent, occurring mainly in the upper gastrointestinal tract. Accidental ingestion accounts for most of the cases, and the severity and extent of damage produced, depends on the composition and volume of the caustic agent ingested; endoscopy is a safe and effective diagnostic procedure. We report four unusual cases of caustic injury of the gastrointestinal tract due to hydrogen peroxide, two cases due to oral ingestion and another two due to the accidental administration of enemas, there was a good clinic and endoscopic recovery with conservative treatment.

Accidents, Occupational↗
PubMed1995

[Epithelioid hemangioendothelioma: a rare indication for liver transplantation?].

A clinical case of epithelioid hemangioendothelioma without extrahepatic involvement treated with liver transplantation is presented. The patient remains alive 42 months thereafter without tumor recurrence. A review of cases reported to date was carried out with special reference being made to the therapy undertaken and the follow-up.

Adult↗
PubMed1995

[Hypertensive colopathy: its endoscopic evaluation and evolution following a liver transplant].

In the last decade the association between intestinal vasculopathy and Portal Hypertension (PH) has been established on the basis of endoscopic, histological and histomorphometric examinations. We report the case of a patient with cirrhosis secondary to hepatitis C virus, in whom colonoscopy demonstrated the presence of colonic vascular lesions with cherry spots appearance in the rectum and left colon that vanished two weeks after liver transplantation. The disappearance of mucosal lesions after liver grafting suggest a relation ship among them and portal hypertension.

Colonic Diseases↗
PubMed1995

[Biliary drainage, a complication of liver transplantation].

We report a case of 49-years-old man with hepatocellular carcinoma treated by hepatic transplantation. In the early post-transplant period severe hepatic dysfunction was detected. Because of the possible vascular origin of the graft lesion, an angiography procedure was performed and hepatic artery thrombosis was identified cholangiography through a T tube showed a large biliary cavity. We analyze the biliary tract reconstruction after liver transplantation, its risk factors and the management.

Carcinoma, Hepatocellular↗
PubMed1995

The retinoblastoma gene product negatively regulates cellular or viral oncogene promoters in vivo.

The protein product of the retinoblastoma tumor suppressor gene (pRb) has been demonstrated to bind transcriptional factors such as E2F and c-Myc protein in vitro. To determine whether pRb regulates both cellular (c-myc) and viral (HPV LCR) promoter activity in vivo, MYC-CAT or HPV LCR-CAT chimeric expression plasmids were generated and cotransfected with a pCMV-RB expression plasmid. pRb repressed both myc and LCR transcription but not SV40-CAT. Transcriptional repression induced by pCMV-RB was relieved by addition of pSV2-E7. Moreover, immunohistochemical assays indicate that in cervical intraepithelial neoplasia lesions, an increased pRb expression correlates with decreased c-myc oncogene expression. These results suggest that pRb can negatively regulate c-myc transcription in vivo in both normal tissue or early cervical lesions. However, in HPV induced invasive cervical carcinomas where viral DNA is integrated expressing its oncoproteins, pRb could be complexed by HPV E7 oncoprotein releasing the repression effect and promoting cell growth.

Cell Line↗
PubMed1994

H-2 allele-specific protection from NK cell lysis in vitro for lymphoblasts but not tumor targets. Protection mediated by alpha 1/alpha 2 domains.

In vivo murine NK cells are known to mediate graft rejection in allogenic as well as in "F1 anti-parental" situations. We have studied an in vitro system based on rIL-2-activated spleen cells and Con A lymphoblast targets in relation to the genetics of F1 hybrid resistance and NK cell activity. We demonstrate that NK cells in this in vitro model are regulated by MHC class I genes in an allele-specific manner at the level of the effector and the target. Using rIL-2-activated effector cells from nude C57BL/6 (B6) and BALB/c mice, we observed no killing of MHC syngeneic lymphoblasts. However, B6 as well as BALB/c lymphoblasts were killed by effector cells from allogeneic nude mice as well as by cells from (BALB/c x B6)F1 hybrids. Experiments that used D8 mice (which carry an H-2Dd transgene on B6 background) and beta 2-m-/- mice demonstrated a direct role for MHC class I molecules at the effector as well as at the target cell level: H-2Dd transgenic effector cells with the typical NK phenotype 3A4+/CD8- killed B6 blasts, but expression of the corresponding H-2Dd transgene in the target lymphoblasts protected them from killing. By using transgenic mice carrying exon shuffled MHC class I transgenes, the protective effect of the H-2Dd molecule was mapped to the alpha 1/alpha 2 domains. MHC class I-deficient lymphoblasts from beta 2-m-/- mice were killed by effectors from all strains of mice, including those matched for MHC. The H-2 class I allele-specific protection in this in vitro assay was observed for lymphoblasts but not for tumor cells, despite the fact that these tumor cells are protected in an allele-specific manner in vivo.

Animals↗
PubMed1994

Resistance to natural killer cell lysis conferred by TAP1/2 genes in human antigen-processing mutant cells.

The human Ag-processing-defective cell line 721.174, and its derivative T2, have a large homozygous deletion in the MHC class II region encompassing the TAP1 and TAP2 as well as the LMP2 and LMP7 genes. A similar, but smaller defect encompassing the TAP1 gene is observed in the 721.134 mutant cell line. With a few recent exceptions, these lines are unable to present endogenous Ag to class I-restricted CD8+ CTL. However, restoration of Ag processing and presentation to CD8+ cytotoxic T cells can be achieved by transfecting TAP1 and TAP2 genes into the T2 and .174 cells, or the TAP1 gene into .134 cells. In contrast to their resistance to MHC class I-restricted CTL-mediated lysis, T2 and .174 as well as .134 cells are highly sensitive to lysis by human NK cells. In the present study, we demonstrate the reversal of the NK-sensitive phenotype of these mutant cell lines upon transfection of TAP genes. The induced NK cell-resistant phenotype, studied in detail with TAP1/2-transfected T2 cells, appeared independent of the MHC class I haplotype of the NK cell donors and was also observed with xenogeneic NK cells. The resistance to NK cell lysis induced by re-expression of TAP1/2 seemed to be independent of the origin of the TAP genes; both human and rat transporters efficiently conferred NK cell resistance. Transfection of single TAP genes to T2 or .174 cells, whether TAP1 or TAP2, did not markedly affect NK cell susceptibility. This indicates that an intact TAP1/2 dimer, and thus efficient peptide translocation into the ER, is necessary for rendering T2 and .174, as well as .134 cells, resistant to NK cell-mediated lysis. Proper translocation of peptides across the ER membrane and loading to class I molecules may represent critical events in rendering an NK-resistant phenotype.

ATP Binding Cassette Transporter, Subfamily B, Mem↗