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M Salcedo

Publications and source records attributed to M Salcedo.

At least 19 recordsLinked to original sources
PubMed2007

The marine sphingolipid-derived compound ES 285 triggers an atypical cell death pathway.

The isolation of new molecules from marine sources opens the door to their possible therapeutic use against tumors and other pathological conditions. Indeed, we recently defined the cytotoxicity of ES 285, obtained from the clam Mactromeris polynima, and its affects on the cells microfilament but not the microtubule network. Considering the analogy between ES 285 and sphingosine-related lipids, we wondered whether ES 285 might affect the activity of PKC at the intracellular level. While we anticipated that ES 285 might inhibit PKC, it turns out that in contrast it serves to activate PKC at the cellular level. Indeed, like other sphingosine-related lipids, ES 285 induces the phosphorylation of MARCKS. Additionally, we further examined the cytotoxicity of ES 285 to elucidate the molecular mechanisms through which this compound triggers apoptosis. When the influence of ES 285 on "cell death markers" was assessed, it became clear that ES285 activates caspase 3 and 12, and that it modified the phosphorylation of p53. In contrast, ES 285 does not affect other pathways widely implicated in regulating cell survival/apoptosis, such as JNK, Erks or Akt. Thus, these data suggest that ES 285-triggers an atypical cell death program when compared to other sphingosine-dependent apoptosis pathways.

Alkanes↗
PubMed2006

Increased intrahepatic and circulating levels of endoglin, a TGF-beta1 co-receptor, in patients with chronic hepatitis C virus infection: relationship to histological and serum markers of hepatic fibrosis.

Endoglin, a transforming growth factor (TGF)-beta1 co-receptor, has been associated with renal and cutaneous fibrosis, as overexpression of this protein has been observed in biopsies from patients with glomerulosclerosis and scleroderma, respectively. Our aim was to evaluate whether endoglin may be associated with hepatic fibrosis featuring chronic hepatitis C virus (HCV) infection. Fifty-two anti-HCV+ patients, five anti-HCV- patients and 27 healthy subjects were studied. Western blot and immunohistochemistry were used to quantify the expression levels of endoglin and TGF-beta1 in liver biopsy samples, and serum concentrations of endoglin and hyaluronic acid were determined by enzyme-linked immunosorbent assays (ELISAs). In patients with advanced fibrosis, intrahepatic expression levels of endoglin and TGF-beta1 were significantly higher than those in patients with early fibrosis (mean: 3- and 5.8-fold, respectively) and normal liver (mean: 3.9- and 12-fold, respectively). Interestingly, activated hepatic stellate cells as well as portal and septal myofibroblasts expressed endoglin. Serum levels of endoglin were also significantly higher in patients with advanced fibrosis than in those with early fibrosis (55.5 +/- 1.6 vs 47.5 +/- 0.9 ng/mL, P < 0.001), showing a positive correlation with serum hyaluronic acid concentrations (r = 0.57, P = 0.01). In conclusion, increased intrahepatic endoglin and TGF-beta1 expression is significantly associated with progressive hepatic fibrosis in chronic HCV infection. Circulating endoglin levels are elevated in HCV patients showing a significant correlation with histological and serum markers of hepatic fibrosis. These data suggest an active role for endoglin in the fibrotic process featuring chronic HCV infection.

Adult↗
PubMed2003

Liver transplantation for fulminant and subfulminant hepatic failure.

AIMS: The aim of this study was to assess the long-term course and outcome after liver transplantation (LTX) for fulminant/subfulminant hepatic failure (FSHF) to determine which factors relate to outcome. PATIENTS AND METHODS: Between April 1990 and October 2002, 30 adult patients with FSHF underwent LTX. King's College criteria were used to decide which patients needed LTX. Pretransplantation parameters (age, sex, degree of hepatic encephalopathy, etiology, and time between onset of symptoms and LTX) were examined as risk factors for LTX outcome. RESULTS: Mean age at LTX was 40.4+/-13.9 years and 46.7% were men. The most frequent causes of FSHF were virus B in 23.3%, autoimmune hepatitis in 23.3%, and cryptogenic in 20%. Fifty percent of the patients with a survival longer than 15 days suffered episodes of acute rejection; chronic rejection occurred in 25%. One- and five-year patient and allograft survival rates for FSHF were 56.3% and 54.7%, respectively. Autoimmune hepatitis was the only factor associated with better posttransplantation outcome, although there were no differences in posttransplant course. Patient survival rates increased during the study period. During the first 5 years (1990-1995) the survival rates were 53.3% (1-year and 5-year), whereas they were 60% at 1 and 5 years in the second interval (1996-2002). CONCLUSIONS: The mortality rate of FSHF is high during the first year post-LTX. LTX for FSHF of autoimmune etiology showed better outcomes with increasing patient survival rates during the study period.

Adolescent↗
PubMed2003

Liver transplantation for autoimmune hepatitis: fulminant versus chronic hepatitis presentation.

AIMS: The aim of this study was to analyse long-term outcomes of patients with liver transplantation for autoimmune hepatitis and to determine if fulminant/subfulminant hepatic failure (FSHF) at presentation was a predictor of outcome after ortothopic liver transplantation. PATIENTS AND METHODS: Between April 1990 and October 2002, 18 patients with autoimmune hepatitis underwent 21 liver transplants. Three patients were excluded because of coexisting causes of hepatitis. Seven patients had FSHF and eight patients had chronic disease. The initial immunosuppressive regimen was cyclosporine based in 80%, and all but one patient received steroids or azathioprine. RESULTS: Mean age at time of transplant was 44.2+/-15.5 years. Patients were followed for 38.9+/-29.6 months. Five patients (33.3%) had seven episodes of acute rejection (two steroid-resistant). Three patients developed chronic rejection. One patient displayed histologically proven recurrent autoimmune hepatitis. Actuarial patient and graft survival rates at 1 and 5 years were 80% and 56% and 78.6% and 51%, respectively. No differences in the clinical characteristics of the patients, rates of acute or chronic rejection episodes, end biliary or arterial complications were observed between FSHF and chronic autoimmune hepatitis. The study suggests a better survival for autoimmune FSHF (P=.003). CONCLUSIONS: Liver transplant is indicated for patients displaying autoimmune chronic liver disease and FSHF with similar clinical courses at however, patients with FSHF at presentation had better survivals.

Acute Disease↗
PubMed2003

[Characterization of de novo malignancies in liver transplantation].

INTRODUCTION: The incidence of de novo malignancies after liver transplantation varies from 3-15%, and is greater than that in the general population. Immunosuppression may play a significant role in the development of most of these tumors. OBJECTIVE: To evaluate the incidence and clinical features of de novo tumors in liver transplant recipients in our center as well as to assess survival. PATIENTS AND METHODS: We retrospectively analyzed 437 liver transplantations (380 patients) performed from April 1990 to July 2001. The incidence of de novo malignancies was 7.4% (n = 28). Four patients presented two different tumors during their lifetime. The etiology of the underlying disease was alcoholic cirrhosis (45.8%), hepatitis C virus cirrhosis (20.8%), hepatitis B virus cirrhosis (12.5%), autoimmune disease (8.4%) and other causes (12.5%). The most frequent neoplasms were cutaneous and epidermoid tumors (21.4% of the malignancies both groups). All the patients with epidermoid tumors and adenocarcinomas were active smokers. The mean age at diagnosis was 58 9 years and this was a factor that influenced tumoral type (adenocarcinomas in older patients and epidermoid tumors in younger patients; p = 0.04). RESULTS: Sarcomas and adenocarcinomas appeared sooner after transplantation than epidermoid and cutaneous tumors (p = 0.04). Fifty percent of the malignancies developed in the second and third year after transplantation. The type of immunosuppression did not influence tumoral type, although most patients received cyclosporin A in combination with azathioprine and/or corticoids. The mean duration of follow-up after diagnosis of the tumor was 23.1 28 months (range, 1-81). Mortality was 58.4% with a median survival of 9 16 months. The actuarial probability of survival at 1, 3 and 5 years was 46.1, 27.7 and 27.7%, respectively. CONCLUSIONS: De novo malignancies are frequent after liver transplantation and their clinical course differs from that in the general population. Because their clinical course is more aggressive, regular follow-up of these patients is essential for early diagnosis.

Adult↗
PubMed2003

Molecular epidemiology of dengue virus type 3 in Venezuela.

During the past 40 years, dengue haemorrhagic fever and dengue shock syndrome (DHF/DSS) have emerged in humans, with approximately 3 million cases reported and over 58 000 deaths. Dengue virus serotypes 1, 2 and 4 (DENV-1, -2 and -4) have been co-circulating in Venezuela for at least the past 10 years, causing minor or major outbreaks of dengue fever (DF) and DHF/DSS. The first recorded outbreak due to DENV-3 in Venezuela dates to 1964 and the virus then seems to have disappeared. However, DENV-3 re-appeared recently (in July, 2000) in Venezuela after 32 years of absence and produced a prolonged major outbreak, which, by the end of 2001, involved 83 180 cases of dengue, mostly DF (92 %). Previous phylogenetic studies revealed that the DENV-3 circulating during the 1960s Latin American outbreak was a genotype V virus. To gain a better understanding of the nature of the current epidemic, the complete sequence was determined of the envelope (E) gene of 15 Venezuelan DENV-3 viruses isolated during 2000 and 2001 from patients presenting with different disease severity. Sequence data were used in phylogenetic comparisons with global samples of DENV-3. Analysis revealed that the strain circulating in Venezuela is closely related to isolates that were previously present in Panama and Nicaragua in 1994 and since then have spread through Central American countries and Mexico. This study also confirms previous reports showing that the DENV-3 strain currently circulating in the Americas is related to the strain that caused DHF epidemics in Sri Lanka and India in 1989-1991 (genotype III). Finally, no evidence of the re-emergence of the strain that circulated in Venezuela in the late 1960s and 1970s (genotype V) was found.

Americas↗
PubMed2003

A simple method for the construction of small format tissue arrays.

Tissue arrays can evaluate molecular targets in high numbers of samples in parallel. Array construction presents technical difficulties and tissue arrayers are expensive, particularly for small and medium sized laboratories. This report describes a method for the construction of 36 sample arrays using widely available materials. A blunted 16 gauge needle for bone marrow aspiration was used to extract paraffin wax cylinders and manually define a 6 x 6 matrix on a blank paraffin wax block. Tissue cores from 36 paraffin wax embedded premalignant lesions and invasive cervical carcinomas were injected into the matrix using a 14 gauge needle. This tissue array was sectioned using a standard microtome and used for the immunodetection of CD44 variant 9 and interleukin 18 with satisfactory results. This method can be applied in any laboratory, without the need of specialised equipment, offering a good alternative for the wider application of tissue arrays.

Biomarkers, Tumor↗
PubMed2001

[Predictive factors of the mortality of digestive hemorrhage caused by esophageal varices in elderly patients].

Complications of liver cirrhosis are increasingly frequent in elderly patients due to increased life expectancy and better management of cirrhotic patients. However, the influence of this condition on the evolution of variceal bleeding has not been well established. The aim of the present study was to determine the characteristics of esophagogastric variceal bleeding in elderly patients and the possible influence of advanced age on hemorrhage-related mortality. We analyzed 321 episodes of variceal bleeding in 227 cirrhotic patients. One hundred and thirteen (35.2%) episodes occurred in patients older than 65 years. No differences were found among patients older or younger than this age in terms of bleeding characteristics or Child-Pugh score. Patients older than 65 years more frequently presented serious associated diseases, hepatocellular carcinoma and hepatic encephalopathy during the episode (52.7% vs. 14%, p < 0.001; 19.7% vs. 8.7%, p = 0.01 and 17.4% vs. 10%, p = 0.09 respectively). Although hemorrhage-related mortality was higher in elderly patients (23.2% vs. 13.5%, p = 0.04), only the Child-Pugh score, definitive hemostasis, hepatocellular carcinoma and the development of encephalopathy or bacterial infection were independent predictive factors of mortality. A considerable proportion of the patients with esophagogastric variceal bleeding were older than 65 years. Advanced age does not independently influence mortality due to variceal bleeding.

Aged↗
PubMed2001

Randomized controlled trial of aspiration needle versus automated biopsy device for transjugular liver biopsy.

PURPOSE: The efficacy and safety of transjugular liver biopsy used to obtain liver specimens in patients with coagulation disorders have been widely proven. However, histopathologic examination is not always possible because of fragmented samples provided by the aspiration technique. Recently, an automated device with a Tru-Cut-type needle was designed. In this randomized controlled trial, the use of this new device is compared with the traditional method in terms of efficacy and safety. METHOD: Fifty-six patients were included in the study; 28 were randomized to undergo the aspiration technique and 28 were randomized to undergo the automated biopsy technique. RESULTS: Correct positioning of the device was achieved in 93% of patients undergoing the aspiration technique and 96% of patients undergoing the automated biopsy technique (P = NS). Mean duration of the procedure and total number of passes were significantly higher in the aspiration needle group than in the automated device group (22.6 min +/- 12.6 vs 15.5 min +/- 9.4; P = .03, and 3.3 min +/- 1.9 vs 1.5 min +/- 0.63; P < .001, respectively). The number of portal tracts was significantly higher in the automated device group (4.7 +/- 2.5 vs. 2.7 +/- 3.4; P < .05). Adequate specimens for histopathologic evaluation were obtained in 26 patients in the automated device group and 24 patients in the aspiration needle group (92.8% vs 85.7%; P = NS), but a definite histopathologic diagnosis was more frequently obtained with the automated biopsy device (68% vs 43%; P = .05). No significant differences were observed in complication rates (7.14% vs. 10.7%; P = NS). CONCLUSION: The automated biopsy device for transjugular liver biopsy is more effective than an aspiration needle in obtaining good samples for a definite histologic diagnosis.

Adult↗
PubMed2001

Intrahepatic expression of inducible nitric oxide synthase in acute liver allograft rejection: evidence of modulation by corticosteroids.

Nitric oxide (NO) has been proposed to have an important role in the immune response. Plasma nitrate levels increase during acute rejection and decrease after treatment with corticosteroids, but little is known about its potential cellular source. We studied inducible NO synthase (iNOS) expression in liver biopsy specimens of 12 patients with acute rejection compared with biopsy specimens from the same patients after treatment with high doses of intravenous corticosteroids. We also compared iNOS expression during acute rejection with a control group (9 patients without histological rejection). iNOS expression was assessed by immunohistochemistry. Intrahepatic iNOS expression was only observed in the cytoplasm of hepatocytes, which were diffusely distributed throughout hepatic lobules. iNOS expression could not be shown in portal tracts, inflammatory cells, or endothelial and sinusoidal lining cells. In patients with acute rejection, iNOS expression was significantly stronger than in the control group (2 +/- 0.7 v 0.6 +/- 0.7; P <.05). After treatment with corticosteroids, iNOS expression decreased significantly (2 +/- 0.7 v 1.3 +/- 0.9; P <.05). In conclusion, the findings of the present study show that during acute liver rejection, hepatocytes are the main cellular source for NO production and treatment with corticosteroids induces significant downregulation of intrahepatic iNOS expression.

Adrenal Cortex Hormones↗
PubMed2001

The non-classical MHC class I molecule Qa-1(b) inhibits classical MHC class I-restricted cytotoxicity of cytotoxic T lymphocytes.

The CD94/NKG2A heterodimer is an inhibitory receptor expressed on a subset of mouse NK cells. CD94/NKG2A recognizes the non-classical MHC class I (class Ib) molecule Qa-1(b) and inhibits NK cytotoxicity. Qa-1(b) presents a peptide derived from the leader sequence of classical MHC class I molecules. Here, we examined the role of CD94/NKG2A in T cell-mediated cytotoxicity. Soluble tetrameric Qa-1(b) bound to almost all CD8(+), but not CD4(+), T cells. This binding seems to be mediated by CD8, because COS cells transfected with CD8 also bound Qa-1(b) tetramer. Therefore, the expression of CD94/NKG2 in T cells was further examined by single-cell RT-PCR. Most murine CD8(+) T cells constitutively expressed CD94 and NKG2A transcripts, whereas they were not detected in CD4(+) T cells. Co-expression of Qa-1(b) and D(k) on target cells significantly inhibited cytotoxicity of D(k)-specific cytotoxic T lymphocytes generated by mixed lymphocyte reaction, indicating that Qa-1(b) on antigen-presenting cells interacts with CD94/NKG2A on CD8 T cells and regulates classical MHC class I-restricted cytotoxic T cells. These results suggest a significant role of CD94/NKG2A as an inhibitory receptor on CD8(+) T cells.

Animals↗
PubMed2001

High prevalence of RET tyrosine kinase activation in Mexican patients with papillary thyroid carcinomas.

RET/PTC oncogene expression is restricted to papillary thyroid carcinomas (PTC). At least three forms of this oncogene have been described. These are generated by the rearrangement of the 5'-terminal region of different expressed genes with the tyrosine-kinase (TK) domain of the ret proto-oncogene. Several studies showing the correlation between the expression of this oncogene, clinical outcome, and histological subtypes have been published. Thirty-five paraffin-embedded PTC samples from patients without a history of radiation exposure were studied. Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to determine a possible correlation between RET activation, clinical outcome, and tumor subtype. Almost half of the studied cases presented with tumoral extension or metastases. Ret gene transcripts and protein were found in all PTC variants as well as in their corresponding metastases. In contrast, none of the follicular adenomas, goiters, or normal follicular cells from the thyroid gland showed evidence of ret activation. We observed a high frequency of ret expression in PTCs, suggesting that ret activation is a common event in nonradiation-related PTC from Mexican patients.

Adult↗
PubMed2001

Differentiation of Ly49s-positive or -negative natural killer cells is inhibited by anti-H-2b monoclonal antibodies acting at the level of bone marrow progenitors from B6 mice.

To investigate the role of MHC class I on in vitro differentiation of natural killer (NK) cells, a CD44low/-CD2-classlow population was isolated from mouse bone marrow. This population, which lacked expression of NK-1.1, Ly49A, Ly49C/I, and Ly49G, generated populations of NK-1.1+ NK cells expressing Ly49A, Ly49C/I, or Ly49G when cocultured for 13 days with syngeneic supportive stromal cells in the presence of interleukin 2. Ly49A and Ly49C/I were absent on the progeny of progenitors tested after 7 days of culture but were expressed as a late event together with low-level expression of NK-1.1, from day 8 of culture. The addition of anti-H-2b monoclonal antibody to cultures at day 0 inhibited proliferation of progenitors supported by either syngeneic, allogeneic, or H-2b-deficient stromal cells, thus suggesting that the effect was not exerted on stromal cells. Additional analyses demonstrated that class Ilow progenitors generated class I+ cells on which the anti-H-2b monoclonal antibody exerted its inhibitory effect.

Animals↗