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Biomedical subjects

M Alvarez

Publications and source records attributed to M Alvarez.

At least 37 records · Page 2Linked to original sources

Using the national cancer institute anticancer drug screen to assess the effect of MRP expression on drug sensitivity profiles.

The MRP gene contributes to one form of multidrug resistance. To identify drugs interacting with MRP, we measured MRP mRNA expression by quantitative PCR in 60 cell lines of the National Cancer Institute Anticancer Drug Screen. Expression was detected in all cell lines (highest in lung carcinomas and central nervous system tumors) with a range of 14-fold. A mean graph of MRP mRNA levels was constructed to determine Pearson correlation coefficients (PCCs) with mean graphs of >40,000 compounds using the COMPARE analysis. Only 20 compounds had PCCs of >/=0.500. The PCCs for VP-16, doxorubicin, and vincristine were 0.008, 0.13, and 0.257, respectively. Initially, 36 compounds with PCCs of >/=0.428 were analyzed using two MRP-overexpressing cell lines; low levels of cross-resistance was demonstrated for 23 compounds (1.3-9.4-fold). Twenty-four compounds also were available for further studies. Using a fluorescence activated cell sorter assay to measure competition of calcein efflux from MRP-overexpressing cells, 10 compounds were found to increase calcein retention by >/=2-fold. Ten compounds also were able to reduce ATP-dependent [3H]LTC4 transport into vesicles from MRP-overexpressing cells. These results contrast with previous studies with MDR-1 in which high correlations were found and confirmed for a large number of compounds. Although other assays may be more revealing, in these unselected cell lines, MRP mRNA expression was a poor predictor of drug sensitivity. This raises the possibility that other factors, including conjugating enzymes, glutathione levels, or other transporters, confound the MRP effect.

ATP-Binding Cassette Transporters

Discrimination of strains of Salmonella enteritidis with differing levels of virulence by an in vitro glass adherence test.

The objective of this study was the in vitro differentiation of isolates of Salmonella enteritidis whose virulences differed in a chick model. A total of 14 strains of S. enteritidis were isolated from either the environment, dairy products, or infected patients. The isolates could be divided into two groups on the basis of their virulence (50% lethal dose) in chickens infected intraperitoneally. When the strains were incubated in adherence test medium (Spanish patent 9700408), only the virulent strains produced aggregates and formed visible filaments attached to the glass tube. These results suggest, although for a limited number of strains, that aggregation in such a medium could be used as a diagnostic tool to discriminate virulent strains of S. enteritidis.

Animals

Differential contribution of HLA-DR, DQ, and TAP2 alleles to systemic lupus erythematosus susceptibility in Spanish patients: role of TAP2*01 alleles in Ro autoantibody production.

OBJECTIVE: To study the influence MHC class II and TAP2 alleles exert on systemic lupus erythematosus (SLE) susceptibility and on the clinical and serological manifestations of the disease, in a cohort of Spanish patients. METHODS: HLA-DR serological typing and HLA-DQA, DQB, and TAP2 DNA sequence specific oligotyping, were carried out in 85 unrelated Spanish SLE patients and 186 healthy controls. Autoantibodies detection was carried out by indirect immunofluorescence and counter immunoelectrophoresis. RESULTS: Total SLE group: the frequency of HLA-DR3 and HLA-DQA1*0501 is significantly increased in this group (pc < 0.005, delta = 0.34 and pc < 0.005, delta = 0.45, respectively) although the highest delta value (delta = 0.87) is obtained when the TAP2*01 alleles are considered. No DQB allele shows significant deviation from the control group. Renal damage: it mainly occurs in HLA-DR3 patients (pc < 0.0005 and delta = 0.72). HLA-DQA1*0501 (p < 0.05, delta = 0.57 and DQB1*0201 (pc NS, delta = 0.56) are weaker susceptibility factors. Ro+ (but not LA) group: this autoantibody response is associated with TAP2*01 alleles in homozygosity (p < 0.05, delta = 0.81). R0/La+ group: it has a different genetic background as HLA-DQA1*0501 (delta = 1) and HLA-DQB1*0201 (delta = 1) are the main susceptibility factors. CONCLUSIONS: A differential association between HLA-DR, DQA1, and DQB1 alleles and SLE or its clinical and serological manifestations are found. Furthermore, the associations are different to the ones reported in other ethnic groups. Finally, TAP2*01 group of alleles are associated with the highest susceptibility to SLE (higher than HLA-DR3) and may influence Ro (but not La) autoantibodies production, whereas HLA-DQA1*0501 and DQB1*0201 mediates concomitant Ro and La productions.

ATP Binding Cassette Transporter, Subfamily B, Mem

Nuclear matrix proteins and osteoblast gene expression.

The molecular mechanisms that couple osteoblast structure and gene expression are emerging from recent studies on the bone extracellular matrix, integrins, the cytoskeleton, and the nucleoskeleton (nuclear matrix). These proteins form a dynamic structural network, the tissue matrix, that physically links the genes with the substructure of the cell and its substrate. The molecular analog of cell structure is the geometry of the promoter. The degree of supercoiling and bending of promoter DNA can regulate transcriptional activity. Nuclear matrix proteins may render a change in cytoskeletal organization into a bend or twist in the promoter of target genes. We review the role of nuclear matrix proteins in the regulation of gene expression with special emphasis on osseous tissue. Nuclear matrix proteins bind to the osteocalcin and type I collagen promoters in osteoblasts. One such protein is Cbfa1, a recently described transcriptional activator of osteoblast differentiation. Although their mechanisms of action are unknown, some nuclear matrix proteins may act as "architectural" transcription factors, regulating gene expression by bending the promoter and altering the interactions between other trans-acting proteins. The osteoblast nuclear matrix is comprised of cell- and phenotype-specific proteins including proteins common to all cells. Nuclear matrix proteins specific to the osteoblast developmental stage and proteins that distinguish osteosarcoma from the osteoblast have been identified. Recent studies indicating that nuclear matrix proteins mediate bone cell response to parathyroid hormone and vitamin D are discussed.

Antigens, Nuclear

[Polymerase chain reaction for rapid detection and serotyping of dengue virus in clinical samples].

This study describes the benefits of using reverse transcriptase polymerase chain reaction (RT-PCR) for the rapid detection and typing of dengue virus in clinical samples. Twenty-seven serum specimens from patients with dengue fever and dengue hemorrhagic fever in Colombia, Nicaragua, and Panama were directly subjected to RT-PCR for the detection of dengue virus. The resulting double-stranded DNA product was typed by a second round of PCR amplification (nested PCR) with type-specific primers, viral culture/indirect immunofluorescence (IIF), and enzyme-linked electroimmunoassay for IgM anti-dengue antibodies. The amplified virus genome was detected and typed within 8 hours. Nested RT-PCR, using viral culture and IIF as the gold standard, showed 100% sensitivity; 78% specificity; 69% positive predictive value, and 100% negative predictive value. It is noteworthy that two of the specimens whose results were positive with nested RT-PCR and negative with viral culture showed specific IgM antibodies. The results of the RT-PCR were in close agreement with those obtained through viral culture. This suggests PCR can greatly facilitate the rapid and early diagnosis of dengue infection.

Colombia

Myocardial interatrial septum loses its epithelial organization by mesenchymal influence. Structural and ultrastructural study.

During atrial septation, the septum primum fuses with the atrioventricular endocardial cushions and myocardial-mesenchymal interactions occur. In order to evaluate the cellular events that take place during this particular interaction a structural, ultrastructural and histochemical study was performed. Our findings indicate that from the fourth day of development, the distal myocardium of the interatrial septum, which interacts with mesenchymal tissue, loses its appearance of an epithelial sheet and becomes a loosely organized tissue. The distal myocytes of the interatrial septum which get progressively separated show features of migratory cells, the final localization of which is the mesenchymal tissue of the adjacent endocardial cushions. These tissue changes involve basal membrane disruption, reduction in the number of desmosomes and intercalated discs with the subsequent appearance of large intercellular spaces between myocytes, myofibrillar disarrangement and acquisition by myocytes of a secretory phenotype characterized by numerous cytoplasmic vesicles. These events occur in a similar way in the atrioventricular canal, where a myocardial-mesenchymal interaction also occurs. In both regions the mesenchymal endocardial cushions and its associated extracellular matrix seem to direct the dissociation of the myocardial tissue and the subsequent migratory cellular behaviour of the interacting myocytes. This is an interesting, and little known, example of a cellular phenotypic transformation during cardiac development.

Animals

[Study of the secretion of P substance, neurotensin and somatostatin in healthy adults].

OBJECTIVE: A study in humans of the profile of physiologic secretion, basal and postprandial of three gastrointestinal peptides has been carried out. METHOD: 20 healthy subjects were studied (9 women and 11 men); any previous digestive pathology has not been included. The study was carried out by determining P substance, neurotensin and somatostatin in plasma by means of RIA I125. The subjects were studied in basal conditions of fasting and the samples were taken at 30, 60 and 90 minutes intervals after the oral intake of a semi-liquid preparation made up of the three immediate principles. RESULTS: It shows the secretion curve of the three gastrointestinal peptides, in a global way and also in relation to sex, age and body weight.

Adult

Description of a new HLA-E (E*01031) allele and its frequency in the Spanish population.

An HLA-E polymorphism study by oligotyping and DNA sequencing was carried out in the Spanish population. As a result, a new HLA-E allele (E*01031) initially assigned by polymerase chain reaction oligotyping as E*0104 was found. This allele presents a synonymous change at codon 77 (AAT-->AAC; Asn) when compared with the E*01032 allele. This position is located in the alpha-helix (alpha 1-domain) and is involved in the peptide binding region of the hypothetical HLA-E molecule. Among 60 Spanish individuals, HLA-E*0101 presents the highest phenotype frequency, followed in decreasing order by E*01032, E*01031 (new allele), and E*0102. Also, new partial intron 1 and complete intron 2 sequences from E*0101, E*01031, and E*01032 are described; the sequences are identical among the three forms. However, the intron 2 sequence of the E*0102 allele bears a two-base deletion not found in apes.

Alleles

Femoral hernia in childhood: review of 38 cases.

Femoral hernias rarely occur at any age, but are extremely rare in infancy. We present 38 cases of femoral hernia treated in our pediatric surgery department during the last 15 years. The number of patients who underwent surgery was high compared with other series reviewed. This might be due to the fact that these hernias were considered in the differential diagnosis of inguinal pathology in childhood. The preoperative diagnosis was correct in 22 cases (57. 8%). After surgical treatment no recurrence was reported.

Child

[Primary cardiac lymphoma: presentation of a case and review of the literature].

We describe a case of primary cardiac lymphoma presenting with chest pain, complete AV block, negative T waves, and infiltration of the basal segments and right free ventricular wall on echocardiography, interpreted initially as hypertrophy. One month later the patient was readmitted with systemic disease and cardiac insufficiency. Furthermore multicentric myocardial infiltration with a nodular mass in the right atrium producing severe tricuspid stenosis was demonstrated. Surgical biopsy was performed and a high grade non-Hodgkin's lymphoma diagnosed. The patient died during the immediate post-operative period without receiving specific chemotherapeutic treatment. Reviewing the published cases, we found that primary cardiac lymphomas are fast growing tumors that infiltrate predominantly the right cavities and have limited therapeutic options.

Fatal Outcome