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N Gutiérrez

Publications and source records attributed to N Gutiérrez.

15 recordsLinked to original sources
PubMed2003

Incomplete DJH rearrangements of the IgH gene are frequent in multiple myeloma patients: immunobiological characteristics and clinical implications.

DH-JH rearrangements of the Ig heavy-chain gene (IGH) occur early during B-cell development. Consequently, they are detected in precursor-B-cell acute lymphoblastic leukemias both at diagnosis and relapse. Incomplete DJH rearrangements have also been occasionally reported in mature B-cell lymphoproliferative disorders, but their frequency and immunobiological characteristics have not been studied in detail. We have investigated the frequency and characteristics of incomplete DJH as well as complete VDJH rearrangements in a series of 84 untreated multiple myeloma (MM) patients. The overall detection rate of clonality by amplifying VDJH and DJH rearrangements using family-specific primers was 94%. Interestingly, we found a high frequency (60%) of DJH rearrangements in this group. As expected from an immunological point of view, the vast majority of DJH rearrangements (88%) were unmutated. To the best of our knowledge, this is the first systematic study describing the incidence of incomplete DJH rearrangements in a series of unselected MM patients. These results strongly support the use of DJH rearrangements as PCR targets for clonality studies and, particularly, for quantification of minimal residual disease by real-time quantitative PCR using consensus JH probes in MM patients. The finding of hypermutation in a small proportion of incomplete DJH rearrangements (six out of 50) suggests important biological implications concerning the process of somatic hypermutation. Moreover, our data offer a new insight in the regulatory development model of IGH rearrangements.

Clone Cells↗
PubMed2001

Early immunophenotypical evaluation of minimal residual disease in acute myeloid leukemia identifies different patient risk groups and may contribute to postinduction treatment stratification.

Early response to therapy is one of the most important prognostic factors in acute leukemia. It is hypothesized that early immunophenotypical evaluation may help identify patients at high risk for relapse from those who may remain in complete remission (CR). Using multiparametric flow cytometry, the level of minimal residual disease (MRD) was evaluated in the first bone marrow (BM) in morphologic CR obtained after induction treatment from 126 patients with acute myeloid leukemia (AML) who displayed aberrant phenotypes at diagnosis. Based on MRD level, 4 different risk categories were identified: 8 patients were at very low risk (fewer than 10(-4) cells), and none have relapsed thus far; 37 were at low risk (10(-4) to 10(-3) cells); and 64 were at intermediate risk (fewer than 10(-3) to 10(-2) cells), with 3-year cumulative relapse rates of 14% and 50%, respectively. The remaining 17 patients were in the high-risk group (more than 10(-2) residual aberrant cells) and had a 3-year relapse rate of 84% (P =.0001). MRD level not only influences relapse-free survival but also overall survival (P =.003). The adverse prognostic impact was also observed when M3 and non-M3 patients with AML were separately analyzed, and was associated with adverse cytogenetic subtypes, 2 or more cycles to achieve CR, and high white blood cell counts. Multivariate analysis showed that MRD level was the most powerful independent prognostic factor, followed by cytogenetics and number of cycles to achieve CR. In conclusion, immunophenotypical investigation of MRD in the first BM in mCR obtained after AML induction therapy provides important information for risk assessment in patients with AML.

Acute Disease↗
PubMed2000

Detection of inv(16) and t(16;16) by fluorescence in situ hybridization in acute myeloid leukemia M4Eo.

BACKGROUND AND OBJECTIVE: It has been established that cytogenetic findings at the time of diagnosis of acute myeloid leukemia (AML) are powerful prognostic indicators. Pericentric inversion of chromosome 16 and translocation t(16;16) resulting in chimeric fusion of CBFB and MYH11 genes are typically seen in the M4-Eo FAB classification subset of AML and are associated with low-risk disease. These subtle chromosomal abnormalities may be difficult to detect in poor-quality metaphase preparations and if missed could lead to incorrect assignment to risk groups and influence the therapy decision-making process. DESIGN AND METHODS: We prospectively studied, at diagnosis, 10 patients with AML-M4 Eo by cytogenetics and fluorescent in situ hybridization (FISH) with two cosmids (36 and 40). As a control group, 7 patients (5 with a diagnosis of AML other than M4 Eo and two cases of reactive eosinophilia) were analyzed. In addition reverse transcriptase chain reaction (RT-PCR) studies were carried out in 6 cases. RESULTS: Karyotypic analysis detected the inv(16) in all but one of the patients with M4-Eo while none of the control cases showed any abnormality on chromosome 16. FISH studies showed that all 10 patients had abnormalities on chromosome 16; the patient with normal karyotype showed an inv(16) by FISH, while a case with inv(16) by cytogenetics had a t(16;16) by FISH. RT-PCR demonstrated amplification of the CBFB/MYH11 product in all cases analyzed. INTERPRETATION AND CONCLUSIONS: In patients with M4Eo and rearrangements of chromosome 16, FISH studies may afford more complete information than conventional cytogenetics and can be an alternative to RT-PCR studies.

Adolescent↗
PubMed1999

GCD14p, a repressor of GCN4 translation, cooperates with Gcd10p and Lhp1p in the maturation of initiator methionyl-tRNA in Saccharomyces cerevisiae.

Gcd10p and Gcd14p were first identified genetically as repressors of GCN4 mRNA translation in Saccharomyces cerevisiae. Recent findings indicate that Gcd10p and Gcd14p reside in a nuclear complex required for the presence of 1-methyladenosine in tRNAs. Here we show that Gcd14p is an essential protein with predicted binding motifs for S-adenosylmethionine, consistent with a direct function in tRNA methylation. Two different gcd14 mutants exhibit defects in cell growth and accumulate high levels of initiator methionyl-tRNA (tRNAiMet) precursors containing 5' and 3' extensions, suggesting a defect in processing of the primary transcript. Dosage suppressors of gcd10 mutations, encoding tRNAiMet (hcIMT1 to hcIMT4; hc indicates that the gene is carried on a high-copy-number plasmid) or a homologue of human La protein implicated in tRNA 3'-end formation (hcLHP1), also suppressed gcd14 mutations. In fact, the lethality of a GCD14 deletion was suppressed by hcIMT4, indicating that the essential function of Gcd14p is required for biogenesis of tRNAiMet. A mutation in GCD10 or deletion of LHP1 exacerbated the defects in cell growth and expression of mature tRNAiMet in gcd14 mutants, consistent with functional interactions between Gcd14p, Gcd10p, and Lhp1p in vivo. Surprisingly, the amounts of NME1 and RPR1, the RNA components of RNases P and MRP, were substantially lower in gcd14 lhp1::LEU2 double mutants than in the corresponding single mutants, whereas 5S rRNA was present at wild-type levels. Our findings suggest that Gcd14p and Lhp1p cooperate in the maturation of a subset of RNA polymerase III transcripts.

Alleles↗
PubMed1999

Randomized prospective study comparing cost-effectiveness of teicoplanin and vancomycin as second-line empiric therapy for infection in neutropenic patients.

BACKGROUND AND OBJECTIVE: The current health-care philosophy dictates that new therapies should always be evaluated for their economic impact. Along with acquisition cost, the cost of delivery, monitoring, adverse effects and treatment failure must also be considered when determining the total cost of therapy. These auxiliary costs can be significant and greatly alter the overall cost of a drug treatment. We conducted a prospective randomized study to evaluate the efficacy, safety and cost of vancomycin and teicoplanin therapy in patients with neutropenia, after the failure of empirical treatment with a combination of piperacillin/tazobactam and amikacin. DESIGN AND METHODS: Seventy-six febrile episodes from 66 patients with hematologic malignancies under treatment, neutropenia (neutrophils <500/mm3) and fever (38 degrees C twice or 38.5 degrees C once) resistant to the combination piperacillin/tazobactam and amikacin were included in the study. RESULTS: Primary success of second-line therapy was obtained in 35 cases (46%) with no significant difference between vancomycin (17/38) and teicoplanin arms (18/38). No difference in renal or hepatic toxicity related to the antibiotic therapy was observed. The average cost per patient according to glycopeptide used was $450+/-180 for the teicoplanin group and $473+/-347 for the vancomycin group. Interestingly, in the teicoplanin arm, drug acquisition accounted for 97% of the total cost, while in the vancomycin arm administration and monitoring play an important role in overall costs. INTERPRETATION AND CONCLUSIONS: In conclusion, our pharmacoeconomic analysis demonstrates that teicoplanin and vancomycin can be administered in neutropenic hematologic patients with similar efficacy and direct costs.

Amikacin↗
PubMed1999

[Ultrastructural identification of Ehrlichia sp in an experimentally infected dog in Venezuela].

This study is the first report made in Venezuela concerning the ultrastructural characteristics of Ehrlichia sp in mononuclear blood cells from an experimentally infected dog. The animal developed clinical manifestations characteristic of the infection, and typical intracitoplasmic inclusion bodies were clearly seen in blood smears stained with modified Giemsa examined by light microscopy. Microorganisms were visualized by transmission electron microscopy. The cytoplasmic inclusions, consisted of membrane-lined vacuole-containing elementary bodies. The organisms were extremely pleomorphic. Elementary bodies were surrounded by two distinct membranes and each was constituted by electro-dense granules. These findings corresponded to the described electron microscopy morphology which characterizes the Ehrlichia genus.

Animals↗
PubMed1993

[The incidence of arrhythmias in young persons without demonstrable heart disease: a 24-hour Holter study in 100 medical students].

A Holter monitorization study was performed in 100 voluntary university students (64 men and 36 women). The mean age was 23.6 years and organic heart disease was ruled out in all cases. Data were analysed in different subgroups including the practice of physical activity and subjects smokers or alcohol consumers. The maximum heart rate (HR) achieved during the wake period was 138.3 +/- 20.43 beat/m. Minimum daytime heart rate was 61.42 +/- 10.32 beat/m and it was below 60 beat/m in 41 subjects. During the nighttime period, the maximum heart rate achieved by the group was 89.34 +/- 11.31 beat/m. Minimum nighttime heart rate was 45.82 +/- 6.35 beat/m. Maximum heart rate in men was 134.3 +/- 21.35 beat/m, while in women was 145.42 +/- 16.36 beat/m. Eighty students presented one or more arrhythmias, among them 28 women and 52 men (p = NS): 92% in sportsmen and women groups as compared with 79% in the non sports practicers, 90% of alcohol consumers and 82% between subjects who smoked and drank, compared with 63% in the non drinkers (p < 0.006). 48% of the subjects presented one or more supraventricular arrhythmias during the daytime or during the nighttime (p = NS). Ventricular rhythm disturbances were found in 20 subjects. There was only one case who had a non sustained ventricular tachycardia of 4 complexes. These disturbances were not increased by practising sport nor by toxic habits. In 15 cases we found sinoatrial block, with a male predominance. Five subjects presented some type of atrioventricular block, 4 of which were alcohol and tobacco consumers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1983

The effect of high altitude on the glycolytic activity of erythrocytes in natives of the Andean Altiplano.

Glucose consumption by anaerobic glycolysis and the pentose pathway were studied in two Aymara populations living at different altitudes (3 600 m and 450 m). The measurements were made both with and without methylene blue. We observed a Pasteur effect for both pathways which may explain the increase in 2-3 DPG and ATP levels found in blood samples from people living at high altitudes. The results in the presence of methylene blue showed a reduced activity of the methaemoglobin reductase system in the high altitude group which may be partly responsible for their increased levels of methaemoglobin.

Adult↗