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Biomedical subjects

C Rivas

Publications and source records attributed to C Rivas.

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

Other cancers in patients with gastric MALT lymphoma.

Patients with Hodgkin's disease and nodal non-Hodgkin's lymphomas seem to have an excess risk for other cancers. A high incidence of other cancers has also been found in some series of patients with gastric MALT lymphomas. In a series of 136 patients with gastric MALT lymphomas the occurrence and features of other cancers have been described. In order to evaluate their occurrence statistically (excluding skin cancers) standard incidence ratios (SRI) have been calculated, using the incidence rates of a Cancer Registry in Spain as a reference. A Cox's multivariate proportional hazard model was fitted in order to evaluate the influence of age, sex, histological grade and treatment with chemotherapy or chemotherapy plus radiotherapy in the development of other non-skin cancers occurring after the diagnosis of MALT lymphoma. Other cancers were detected in 16 of the 136 patients (11.7%); the other cancer was detected prior to MALT gastric lymphoma in 6 patients (4.41%), concomitantly in 4 (2.9%) and after diagnosis of the lymphoma in 6 (4.41%). Other cancers occurred in 14.4% of the male and in 8.3% of the female patients; in 12% of the patients with low grade and in 11% of the patients with high grade lymphomas. Of the 6 cancers that occurred after diagnosis of the gastric lymphoma, 3 did in the 80 patients (3.7%) that had been treated with chemotherapy, 1 in the 3 cases (33%) treated with chemotherapy and radiotherapy and 2 in the 53 patients (3.7%) who had not received chemotherapy or radiotherapy. The most frequent other cancers were lymphoid neoplasms and gastric carcinoma. There was not an excess of other cancers in the whole cohort or in the sex or histological grade strata. There was an excess close to significance (SIR =2.59; 95% CI:0.98-6.88) in the patients under 50 years of age. In the Cox's analysis, age, sex, histological grade and treatment did not influence the occurrence of other cancers after the diagnosis of lymphoma. In conclusion, in patients with gastric MALT lymphoma other cancers also occur. An excess incidence was not demonstrated, although it may exist in patients under 50 years. Of special importance is the occurrence of gastric cancer that appears concomitantly or after gastric lymphoma.

Adenocarcinoma↗
PubMed1998

Increased C-MYC oncogene copy number detected with combined modified comparative genomic hybridization and FISH analysis in a Richter syndrome case with complex karyotype.

Modified comparative genomic hybridization (mCGH) was performed in a Richter syndrome case with a complex karyotype to identify and map gains of DNA sequences with possible importance in the pathogenesis and progression of the tumor. The mCGH analysis revealed a more intense signal on part of the long arm of one pair of chromosomes belonging to group C. The G-banding study showed that the increased DNA-sequence copy number originated from the 8q22-->qter chromosomal region. This increase was confirmed by performing a fluorescence in situ hybridization analysis on tumor metaphases by first using a chromosome 8-specific library and subsequently a C-MYC probe, which revealed positive staining on six different regions located on six different chromosomes, each one bearing a single copy of the C-MYC oncogene. These results show the existence of C-MYC oncogene copy-number increases and confirm the usefulness of mCGH in the genetic analysis of malignancies.

Aged↗
PubMed1998

Vaccinia virus E3L protein is an inhibitor of the interferon (i.f.n.)-induced 2-5A synthetase enzyme.

Induction of apoptosis in mammalian cells by double-stranded (ds) RNA-dependent enzymes, protein kinase (PKR), and 2-5A-synthetase/RNase L (referred to as the 2-5A system) might be a mechanism mediating anticellular and antiviral actions of interferon (i.f.n.). To counteract the effect of i.f.n., animal viruses have acquired genes that block specific i.f.n. pathways. Among poxviruses, vaccinia virus (VV) encodes E3L, a dsRNA-binding protein, which inhibits activation of i.f.n.-induced PKR. It has been proposed that E3L might also block activation of the 2-5A system, but direct proof is lacking. To establish if E3L inhibits the 2-5A system, we have developed a method to assay apoptosis induced by increased production of enzymes in the 2-5A pathway, as well as of their putative modulators. This assay is based on the use of cells derived from homozygous PKR knockout mice (Pkr-/-) infected with a VV mutant lacking E3L (delta E3L) and transiently transfected with a luciferase reporter gene together with plasmid vectors expressing 2-5A-synthetase, RNase L, or E3L, all controlled by the same inducible promoter. We found that expression of 2-5A-synthetase inhibited luciferase activity in a dose-response manner, reaching inhibition values of 80% relative to transfections with control plasmids. Similar results were obtained by transfection with an RNase L vector, although in this case the extent of inhibition was further enhanced upon coexpression of 2-5A-synthetase and RNase L. Inhibition of protein synthesis mediated by the 2-5A system correlated well with induction of apoptosis. Transfection of cells with a plasmid vector expressing E3L together with 2-5A-synthetase completely prevented apoptosis induced by this enzyme. We conclude that VV E3L acts as an inhibitor of the i.f.n.-induced 2-5A-synthetase enzyme.

2',5'-Oligoadenylate Synthetase↗
PubMed1998

Hypermethylation of p15/ink4b/MTS2 gene is differentially implicated among non-Hodgkin's lymphomas.

P15 (MTS2) gene is a candidate tumor suppressor gene localized adjacent to the p16 gene at 9p21. Deletions at the 9p21 region frequently affect both p16 and p15 genes, however, mutations in the coding sequence of the p15 gene have not been found in the majority of tumors analyzed, including non-Hodgkin's lymphomas. Abnormal methylation of the promoter region of p15 has been recently described as an alternative mechanism of inactivation of this gene. We analyzed 72 non-Hodgkin's lymphomas (NHL) for methylation at p15 exon 1 by PCR and Southern blot techniques using methylation-sensitive restriction enzymes. Abnormal methylation was found in eight cases (11%), most of them (three MALT, one anaplastic T cell lymphoma, one Burkitt and one follicular lymphoma) showing hypermethylation in the p16 gene also. In contrast, two pleomorphic T cell NHL showed a selective methylation at p15 gene, while the p16 gene remained unmethylated. The results show that methylation at the p15 gene is frequently associated with p16 methylation in NHL, and suggest that selective methylation of p15, although uncommon, could be a specific alteration implicated in T cell NHL.

Carrier Proteins↗
PubMed1998

[Correlation of flow and static cytometry; their application to the study of anaplastic lymphomas].

PURPOSE: DNA study by cytometric methods is one of the prognosis factors considered in malignant tumours. Flow cytometry (FCM) was the most frequently used techniques in cell suspensions. Image cytometry (ICM) was also applied in cellular smears and it is possible to measure the results with an Image Analyzer, which supposes a substancial advantage over DNA studies. To confirm the results and correlation of the two techniques a controversial subtype of lymphoid tumour was selected: Anaplastic large cell lymphoma (ALCL). MATERIAL AND METHODS: Fifty four cases of ALCL (23 classical type and 31 ACL-Hodgkin related) were studied. Cytometry was performed in paraffin-embedded tissues previously dewaxed, rehydrated and minced. FCM was done in suspensions incubated with ribonuclease A and stained with propidium iodide in an EPICS-C flow cytometer. ICM study was performed in Feulgen-stained smears and measured by an Image Analyzer CAS-200. RESULTS: All cases were aneuploid. ALCL were 30.5% hypodiploid (HpD) and 69.5% hyperdiploid (HrD) by FCM; 43.5% HpD and 56.5% HrD by ICM. ALCL-HR were 58% HpD and 42% HrD by FCM; 68% HpD and 32% HrD by ICM. There was a lack of correlation of 22% between both methods but it was not statistically significant. CONCLUSIONS: We can conclude the obtained results by FCM and ICM are almost similar.

Aneuploidy↗
PubMed1998

Prevention of rotavirus diarrhoea in foals by parenteral vaccination of the mares: field trial.

Many countries have reported rotavirus diarrhoea in foals. In Argentina it causes important economic losses to the horse industry. In this work we present the results obtained using an experimental vaccine in a farm with enzootic infection of rotavirus. A hundred mares were vaccinated 60 and 30 days before foaling with inactivated rotavirus SA11 (G3P2), H2 (G3P12), Lincoln (G6P1), with aluminum hydroxide as adjuvant; 65 mares were included in the unvaccinated, control group. To evaluate the vaccine, morbidity, duration of the diarrhoea and rotavirus shedding were recorded. Antibody levels were established in serum, colostrum and milk of the vaccinated mares, and also in serum from the foals. In foals from vaccinated mares the morbidity was 30%, clinical signs were observed during 1.8 days, and rotavirus shedding was not detected. In the control group the morbidity reached 80%, the clinical signs lasted 7.3 days and rotavirus shedding was detected in 80% of the diarrhoeic foals. At foaling the serum antibody levels were 15 times higher with a mean neutralizing titre (NT) of 3.5 logs than before vaccination (2.4 logs), in colostrum 5.00 logs, and in milk at 90 days post partum 1.7 logs. In foals from vaccinated mares the level of neutralizing antibodies was 3.8 logs at 48 days of age, going down to 2.2 logs at 90 days of age. Immunization of the pregnant mare would be a good method for preventing diarrhoea in foals.

Animals↗
PubMed1998

Effects of orange and apple pectin on cholesterol concentration in serum, liver and faeces.

To investigate the effects of pectin on cholesterol metabolism, normal rats were fed for three weeks a diet containing 2.5 or 5 % apple or orange pectin, or without pectin (control). Cholesterol concentrations were determined in faeces after 1, 2 and 3 weeks of treatment, and in liver and serum at the end of the experimental trials. Cholesterol concentration in faeces showed a significant increase by week 3 in rats fed 5 % orange or apple pectin. Hepatic cholesterol concentration declined significantly in all pectin-fed groups. Serum cholesterol only declined significantly in apple-fed groups. The decrease of cholesterol levels in liver and serum, and its increase in faeces could explain the beneficial effect of including these fibers in the diet to prevent some nowadays very frequent diseases.

Animals↗
PubMed1998

[Application of modified comparative genomic hybridization in the genetic analysis of 5 lymphoid neoplasms].

To analyze the utility of performing modified comparative genomic hybridization (mCGH) as a complementary technique to conventional cytogenetic techniques in the genetic analysis of lymphoid neoplasms. Modified comparative genomic hybridization and subsequent FISH techniques were performed in 5 lymphoid neoplasms cases diagnosed in Fundación Jiménez Díaz. The latter was done in order to confirm the results obtained with mCGH. Gains of chromosomal regions not detected with conventional cytogenetic techniques were detected by mCGH. A good correlation in the results obtained between conventional cytogenetic and mCGH techniques was observed. Nevertheless, mCGH enables the detection and subsequent identification of gains of genetic sequences undetectable with cytogenetic techniques with possible diagnostic and prognostic value.

Chromosomes, Human, Pair 10↗
PubMed1997

Frequent allelic losses of 9p21 markers and low incidence of mutations at p16(CDKN2) gene in non-Hodgkin lymphomas of B-cell lineage.

We present an allelotype analysis of 35 cases of non-Hodgkin lymphomas and normal pairs using four microsatellite markers that flank the region occupied by the CDKN2 gene locus at 9p21. Frequent allelic losses (LOH) were detected in B-cell lineage NHLs, including Burkitt lymphoma (33.3% of total, if we only consider high grade tumors). In five of these tumors LOH did not include the CDKN2 gene. Mutational analysis of exon 1 and 2 of CDKN2 (SSGP and sequencing of abnormal bands) revealed a nonsense mutation (Arg72Ter) in one tumor (case 10), where the second hit of the Knudson's model consisted of the elimination of the wild type allele. In view of these results, the hypothesis of two different candidate tumor suppressor gene regions around the CDKN2 locus remains an intriguing possibility.

Alleles↗
PubMed1997

Activation of the IFN-inducible enzyme RNase L causes apoptosis of animal cells.

The interferon (IFN)-induced enzyme RNase L produced by a recombinant vaccinia virus (VV) causes death of mammalian cells with morphological and biochemical characteristics of apoptosis. Coexpression of 2-5A-synthetase enhances apoptosis induced by RNase L Activation of endogenous RNase L by infection with a VV ts mutant (ts22) or with wild-type virus in the presence of the antipoxvirus drug isatin-beta-thiosemicarbazone, a treatment known to significantly increase the amount of double-stranded RNA late during infection, also causes pronounced apoptosis of infected cells. The effects observed with recombinant virus-derived RNase L or with the endogenous enzyme are specific, since apoptosis also occurs in cells derived from mice lacking the IFN-induced protein kinase (PKR). The apoptosis antagonist Bcl-2 prevents induction of cell death by RNase L activation. Apoptosis of mammalian cells by RNase L activation could be a mechanism mediating anticellular actions of IFN.

2',5'-Oligoadenylate Synthetase↗
PubMed1997

Inducible expression of the 2-5A synthetase/RNase L system results in inhibition of vaccinia virus replication.

Studies of interferon (IFN)-treated virus-infected animal cells have revealed the 2-5A system (2-5A synthetase/RNase L enzymes) as being responsible for virus inhibition only in the case of picornaviridae. To investigate whether those IFN-induced enzymes could be responsible for inhibition of poxvirus replication, we have generated recombinant vaccinia viruses (VV) containing the corresponding genes (VV-2-5AS and VV-RL, respectively). RNase L produced in cells infected with VV-RL leads to rRNA degradation and inhibition of virus protein synthesis, which correlates with about 92% reduction in virus yields by 48 hr after infection. Combined expression of this enzyme with 2-5A-synthetase further inhibits virus yields. The pattern of rRNA fragments produced by infection with viruses VV-RL and/or VV-2-5AS is the characteristic for activation of the 2-5A pathway by IFN treatment. Combined infection of VV-RL together with vesicular stomatitis virus (VSV) demonstrates this inhibition to be specific for VV and not due to a general effect. Breakdown of rRNA is largely due to the recombinant vector-derived enzyme, since a C-terminal deletion mutant of RNase L is inactive and the extent of rRNA degradation induced by infection with VV-RL is similar in cells treated or not with IFN. Moreover, the anti-VV effects of RNase L is also observed in a cell line lacking the endogenous ds RNA-dependent protein kinase (PKR). Thus, our findings provide direct evidence for antiviral activity of the 2-5A system on poxviruses.

2',5'-Oligoadenylate Synthetase↗
PubMed1997

Correlation between mutations in p53 gene and protein expression in human lymphomas.

A discordance between p53 protein overexpression and the presence of mutations in the gene has been observed in many types of tumors, including human lymphomas. To probe this finding, we have studied a large series of 94 lymphomas of different pathologic types and histologic differentiation. Analyzing exons 5-9, we have found mutations in the p53 gene in 7 of 94 cases distributed in different subtypes: 4/12 (33%) high-grade B-cell non-Hodgkin's lymphomas (B-NHLs), in 1 of 5 (20%) high-grade mucosa-associated lymphomas (MALT), in 1 of 22 (4.5%) anaplastic large cell lymphoma (ALCL), and in 1 of 24 (4%) T-cell NHLs. Immunostaining with anti-p53 antibody DO-7 was possible in 87 lymphomas, and overexpression of p53 protein was observed in 16 cases (18%). A discrepancy between the results of SSCP and immunostaining was detected on 18 tumor samples. Two cases with mutations in the gene showed no altered protein expression and 16 cases overexpressed p53 protein had no point mutations. In these cases, the possibility that mutations occur outside the exons studied has been tested and the entire coding sequence analyzed. Only one case showed a mutation in exon 10, and we found two cases carrying a polymorphism in exon 4 and in intron 10. We conclude that mutations in p53 occur mainly in high-grade B-cell NHLs. Although not limited to a specific subtype of lymphoma, they may be rare in Hodgkin's disease and in low-grade lymphomas. The discrepancies between overexpression and presence of mutations suggest (1) the existence of another mechanism to stabilize the p53 protein, and (2) that the immunohistochemistry cannot be used to predict mutations in the gene.

Antibodies, Monoclonal↗
PubMed1997

Hypermethylation of a 5' CpG island of p16 is a frequent event in non-Hodgkin's lymphoma.

Hypermethylation of a 5' CpG island of p16 gene has been recently described as a possible way of inactivation of this tumor suppressor gene, alternative to deletions and mutations. We have investigated if hypermethylation of a 5' CpG island of p16 occurs in non-Hodgkin's lymphoma (NHL) and normal lymphoid tissue. A total of 82 NHLs were examined for p16 methylation by Southern blot and PCR analysis. Hypermethylation was detected in approximately 20% of B cell lymphomas of both low and high grade and in 15% of T cell NHL. The highest rate of p16 gene methylation in tumors was found among MALT (mucosa-associated lymphoid tissue) lymphomas in which the percentage of cases with p16 gene methylation reached 67%. However, normal lymphoid tissue was always unmethylated at p16 locus. These results indicate that p16 gene methylation is a frequent event in NHLs, mainly in MALT lymphomas, and suggest that it could be an important mechanism of inactivation of this gene.

Binding Sites↗
PubMed1997

[Value of protein 53 expression in lymphoma. Its correlation with genetic mutations].

PURPOSE: p53 is a tumour suppressor gene encoding a nuclear phosphoprotein that plays an important role in the control of normal cell proliferation. We have tried to establish the value of expression of the p53 protein in malignant lymphomas and its correlation with the presence of structural gene abnormalities. MATERIAL AND METHODS: 230 cases of lymphomas (11 Hodgkin's disease and 219 non-Hodgkin's) were studied by immunohistochemistry using an anti-p53 monoclonal antibody (DO-7, DAKO). Sections were heated by pressure cooker in 0.01 M sodium citrate buffer pH 6 as a method for antigen unmasking. The quantification of levels of nuclear p53 protein were measured with an Image Analyzer (CAS-200, Becton-Dickinson S.A.). We have also searched for mutations in a series of 94 lymphomas using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis in exons 5 to 9 of the p53 gene and the sample showing abnormal pattern were sequenced. RESULTS: p53 immunoreactivity has been detected in 82.6% of cases. The percentage of positive cells varies in a wide range which was divided into 0% (17.39%), less than 5% (57.39%), between 5-10% (13.91%) and more than 10% (11.30%). In all lymphoma subtypes, we have found the majority of cases show levels less than 10% and few more than 10%. We found abnormal bands in 9 of 94 lymphomas with different diagnosis (1 ALCL, 1 T-LNH, 2 B-LNH, 2 centroblastic, 1 lymphoblastic and 2 MALT). Two cases resulted to be a silent base change which not alter the function of the p53 protein and represent a common polymorphism. Seven cases showed single base pair missense mutations in all of them. Mutations in codons 179, 248 and 273 correspond to some of the typical hotspots described in p53 gene. CONCLUSIONS: p53 expression, is a frequent finding in malignant lymphomas, is variable and relates to histological subtype. The results suggest that positive immunocytochemistry cannot be used to determine which tumours have mutations of p53 because the existence of cases with discrepancies between overexpression of the protein and presence of mutations.

DNA Mutational Analysis↗
PubMed1996

African swine fever virus gene A179L, a viral homologue of bcl-2, protects cells from programmed cell death.

The African swine fever virus (ASFV) open reading frame A179L, which is similar to the human proto-oncogene bcl-2, has been cloned and expressed in vaccinia virus under control of the pEIL synthetic early/late promoter. The A179L gene product prevented cell death in HeLa and BSC-40 cells doubly infected with another recombinant vaccinia virus expressing the interferon-induced double-stranded RNA-activated protein kinase (p68 kinase), which activates a rapid cell death characteristic of apoptosis. This finding suggests that the A179L gene has a function similar to that of bcl-2 in preventing apoptosis and may play an important role during productive ASFV infection.

African Swine Fever Virus↗
PubMed1996

Incidence of homogeneously staining regions in non-Hodgkin lymphomas.

We report a series of 86 non-Hodgkin's lymphomas (NHL) studied cytogenetically in which two cases with a homogeneously staining region (HSR) located on chromosome 19 and on chromosome 1, respectively, were observed. The low incidence detected (2.3%) suggests that HSR are rare events in NHL. An oncogenetic amplification study was performed with probes for genes that are currently known to undergo amplification and with probes for two genes located on chromosome 19q (AKT2 and BCL-3). We detected no amplification except for AKT2 putative oncogene in the lymphoma in which the HSR was located on chromosome 19. Because amplification of AKT2 putative oncogene has been detected in ovarian carcinomas bearing HSR and in this case NHL, we believe that this gene may be implicated in the pathogenesis of other neoplasias in cooperation with other genes. Further investigation is needed to confirm the low incidence of HSR in NHL and the origin of the amplified material.

Adult↗