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J Benítez

Publications and source records attributed to J Benítez.

At least 73 records · Page 4Linked to original sources
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

Mutation analysis of the BRCA2 gene in breast/ovarian cancer Spanish families: identification of two new mutations.

The recently isolated gene BRCA2 is responsible for about 45% of familial breast cancer and the majority of male breast cancer families. We have screened 12 high risk breast/ovarian Spanish families for mutations in BRCA2, using SSCP followed by direct sequencing. We have found mutations in four of our 12 families (33.3%), including two with male breast cancer. Three of the mutations were frameshift and one was a missense. Two of the mutations have been previously published and two are new mutations.

Adult↗
PubMed1997

Single point dilution method for the quantitative analysis of antibodies to the gag24 protein of HIV-1.

In the present work a concept proposed in 1992 by Dopotka and Giesendorf was applied to the quantitative analysis of antibodies to the p24 protein of HIV-1 in infected asymptomatic individuals and AIDS patients. Two approaches were analyzed, a linear model OD = b0 + b1.log(titer) and a nonlinear log(titer) = alpha.OD beta, similar to the Dopotka-Giesendorf's model. The above two proposed models adequately fit the dependence of the optical density values at a single point dilution, and titers achieved by the end point dilution method (EPDM). Nevertheless, the nonlinear model better fits the experimental data, according to residuals analysis. Classical EPDM was compared with the new single point dilution method (SPDM) using both models. The best correlation between titers calculated using both models and titers achieved by EPDM was obtained with the nonlinear model. The correlation coefficients for the nonlinear and linear models were r = 0.85 and r = 0.77, respectively. A new correction factor was introduced into the nonlinear model and this reduced the day-to-day variation of titer values. In general, SPDM saves time, reagents and is more precise and sensitive to changes in antibody levels, and therefore has a higher resolution than EPDM.

Enzyme-Linked Immunosorbent Assay↗
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

A region of allelic imbalance in 1q31-32 in primary breast cancer coincides with a recombination hot spot.

Previous studies have shown that the 1q31-32 region frequently presents allelic imbalance (AI) in various neoplastic diseases, such as breast cancer, medulloblastoma, male germ cell tumors, and renal collecting duct carcinoma, suggesting the presence of a tumor suppressor gene in this location. We used 19 informative microsatellite markers to analyze 33 primary breast tumors for AI in the 1q31-32 region. Our results demonstrate a 10-cM critical region of AI that is present in more than 60% of the tumors. This region is located proximal to the REN locus and is flanked by the CACNL1A3 and D1S2655 markers. Most important, the critical region of AI coincides with a female hot spot of recombination, suggesting a possible correlation between the two regions.

Alleles↗
PubMed1997

[A clinical, cytogenetic and molecular study of 10 patients with the Prader-Willi syndrome].

BACKGROUND: The Prader-Willi syndrome (PWS) is a neurogenetic disorder associated with abnormalities in the chromosomal region 15q11-13 of paternal origin. Most cases (65-85%) have a deletion involving the paternally derived chromosome and the remainder (20-25%) have a maternal uniparental disomy. Some patients have a defect in the imprinting process. We report the results of molecular, cytogenetic and clinical studies on 10 PWS patients. PATIENTS AND METHODS: 18 suspected patients were classified as PWS typical or not typical as they fulfilled or not the clinical criteria for PWS. Cytogenic studies-high resolution chromosome banding analyses (HRGTG) and fluorescence in situ hybridization (FISH) -and molecular chromosome genetic analyses--microsatellite markers and Southern blotting--were carried out from peripheral blood lymphocytes. RESULTS: PWS was confirmed in 10 probands. 8 fulfilled the clinical criteria for PWS and showed cytogenetic and/or molecular abnormalities. In 2 patients without clinical or cytogenetic data, diagnosis was confirmed by molecular methods only. Cytogenetic and molecular findings describe a characteristic clinical picture of PWS. CONCLUSIONS: Cytogenetic techniques (FISH and HRGTG) confirmed PWS diagnosis in 40% of cases, microsatellite studies in 70% of them and Southern blotting (the metilation test) in 100% cases. Southern blotting is the method of choice for rapid diagnostic testing of patients suspected of having PWS.

Adolescent↗
PubMed1997

A high-resolution map of the regulator of the complement activation gene cluster on 1q32 that integrates new genes and markers.

Sixteen microsatellite markers, including two described here, were used to construct a high-resolution map of the 1q32 region encompassing the regulator of the complement activation (RCA) gene cluster. The RCA genes are a group of related genes coding for plasma and membrane associated proteins that collectively control activation of the complement component C3. We provide here the location of two new genes within the RCA gene cluster. These genes are PFKFB2 that maps 15 kilobases (kb) upstream of the C4BPB gene, and a gene located 4 kb downstream of C4BPA, which seems to code for the 72 000 Mr component of the signal recognition particle (SRP72). Neither of these two genes is related structurally or functionally to the RCA genes. In addition, our map shows the centromere-telomere orientation of the C4BPB/MCP linkage group, which is: centromere-PFKFB2-C4BPB-C4BPA-SRP72-C4BPAL1++ +-C4BPAL2-telomere, and outlines an interval with a significant female-male recombination difference which suggests the presence of a female-specific hotspot(s) of recombination.

Chromosome Mapping↗
PubMed1997

Detection of trisomy 8 using conventional cytogenetic techniques and interphase FISH analysis in 34 myeloid disorders: a comparative study.

Trisomy for chromosome 8 is one of the most common chromosome abnormalities detected in myeloid disorders. However, and despite its great incidence, its biologic significance remains poorly understood. Recently, some reports have shown the existence of masked trisomy 8 in myeloid disorders. To try to detect occult trisomy 8, we performed a study in which 34 myeloid disorders with apparent normal karyotypes using conventional cytogenetic techniques were analyzed using fluorescence in situ hybridization (FISH) analysis. Masked trisomy 8 was not detected in any of the 34 cases studied. This suggests that trisomy 8 may be a rare event in myeloid disorders in which an optimal conventional cytogenetic analysis has been performed. The acquisition of trisomy 8 either in early neoplastic stages in some cases or in late neoplastic stages in others and the absence of masked trisomy 8 suggest that this chromosome alteration may not be essential to the development of myeloid disorders.

Bone Marrow↗
PubMed1997

CYP2D6, NAT2 and CYP2E1 genetic polymorphisms in nonagenarians.

BACKGROUND: enzymatic polymorphisms affecting the metabolic disposition of xenobiotics may modulate the rate of activation or deactivation of carcinogens and other toxic environmental chemicals. Hence, these polymorphisms may influence the risk of suffering some types of cancer and other degenerative diseases that are incompatible with extreme longevity. AIMS: to establish the distribution of three well known enzymatic polymorphisms that affect the CYP2D6, NAT-2 and CYP2E1 genes and the activity of their enzymatic gene products, involved in the disposition of many xenobiotics, in a group of nonagenarians and in much younger controls. PATIENTS: the three genotypes were determined in 41 nonagenarians (10 males, mean age 92.2 years, range 90-98) free of known malignancies or neurodegenerative diseases. The control groups comprised 217 healthy volunteers (128 males, mean age 36.3 years; SD, 12.7) for the CYP2D6 and NAT2 genotypes and 137 (116 males, mean age 32 years; SD, 18.8) for the CYP2E1 genotype. METHODS: after extraction of DNA from white blood cells, polymerase chain reaction and restriction fragment polymorphism methods were used to identify the allelic variants of the three genotypes. RESULTS: we found no qualitative or quantitative difference in the mutations underlying the three genetic polymorphisms studied, nor in the expected enzymatic phenotypes. Instead, a close parallelism exists between advanced age and younger groups. CONCLUSION: longevity does not seem to be related to any special configuration of these three polymorphic traits. Comparisons with younger controls may be adequate when studying the distribution of these polymorphisms in diseases affecting old people. No genetically determined differences in the activation of drugs metabolized by these enzymes are to be expected in very old people.

Aged↗
PubMed1997

Senile chorea: a multicenter prospective study.

Senile chorea (SC) is characterized by the presence of late onset, generalized chorea with no family history and no dementia. It is unclear whether it is a distinct clinical entity or represents late onset Huntington's disease (HD) with an undetected family history. In order to clarify this issue, we carried out a prospective, multicenter study of suspected cases of SC. Since 1994 we identified six cases that met clinical criteria for SC. Their study included routine lab tests, cerebral MRI, neuropsychological assessment, and lastly gene IT15 analysis. An abnormal expansion of the (CAG)n repeat was found in three patients. Although there were no criteria for dementia, most neuropsychological tests revealed mild to moderate deficits, particularly in visuospatial and prefrontal tasks, m all six patients, those that were finally diagnosed as having late onset "sporadic" HD, but also in patients that finally had SC. This study provides further evidence on the existence of SC; however, the distinction from late onset "sporadic" HD seems not to be possible on clinical grounds unless a genetic study is carried out. Some cases of suspected "SC" have late onset "sporadic" HD.

Age of Onset↗
PubMed1997

The 12 base pair duplication/insertion alteration could be a regulatory mutation.

A wide array of mutations now numbering more than 200 have been identified in the BRCA1 gene, one of the two breast cancer susceptibility genes identified so far. In addition, there have been several variants described but it is not known if they really represent functionally significant mutations of the BRCA1 gene. We report evidence to show that the duplication/ insertion of 12 base pairs in intron 20 could have a real effect on expression of the BRCA1 gene, although it was also present in 1% of our control population.

Adult↗
PubMed1997

CYP2D6 polymorphism is not associated with essential tremor.

Recent reports have shown an association between cytochrome P450IID6 (CYP2D6) polymorphism and Parkinson's disease. We investigated the association between this polymorphism and the risk for developing essential tremor (ET). Leukocytic DNA from 91 unrelated ET patients and a control group of 258 unrelated healthy individuals was studied for the occurrence of eight different CYP2D6 allelic variants by using allele-specific PCR amplification Xbal and EcoRI-RFLP's analyses. The prevalence for these allelic variants in the ET and control groups were, respectively: CYP2D6*1 76.9 and 78.7%, CYP2D6*2 0.5 and 0.2%, CYP2D6*3 0 and 1%, CYP2D6*4 12.1 and 12.2%, CYP2D6*5 1.6 and 1.7%, CYP2D6*9 4.4 and 2.9%, CYP2D6*2x2 4.4 and 3.2%. The prevalence of subjects with absent CYP2D6 activity (those carrying two defect genes) was 1.1 and 3.1% in ET and control groups, respectively. Both groups studied were in Hardy-Weinberg equilibrium. These results indicate that mutations at the CYP2D6 gene do not seem to be a major factor in determining susceptibility to ET, and reinforces the view that ET and parkinsonism are distinct conditions.

Adolescent↗
PubMed1997

Tryptamine: a possible endogenous substrate for CYP2D6.

The fact that CYP2D6 is not only expressed in liver but also in brain and the clinical association of this cytochrome with Parkinson's disease suggests the possibility of existence of some endogenous substrate, and among these perhaps one or more neurotransmitters could be metabolized by CYP2D6. In this study we explored such a possibility by studying the modulation of CYP2D6 activity by several neurotransmitters. Our findings confirm the occurrence of a competitive inhibition of dextromethorphan O-demethylation in the presence of tryptamine, with a Ki value of 44.6 microM. Tryptamine was metabolized in human liver microsomes by an enzyme activity with a K(m) of 3.6 +/- 0.9 microM. Such activity is NADPH dependent and is inhibited by quinidine and CYP2D6-specific substrates. The product of the reaction is tryptophol. These results suggest that tryptamine may be an endogenous substrate of CYP2D6.

Cytochrome P-450 CYP2D6↗
PubMed1997

[Anomalies of the facial nerve].

An anomaly of the tympanic segment of the facial nerve in an adult cadaver specimen is reported. The second portion of the facial nerve crossed between the stapedal pillars. The rarity of this anomaly, particularly in a well constituted temporal bone, is discussed.

Facial Nerve↗
PubMed1997

[Primary stent treatment in the acute phase of myocardial infaction].

INTRODUCTION: Although direct balloon angioplasty has emerged as an alternative to thrombolytic therapy in patients with acute myocardial infarction, reocclusion and restenosis rates are limiting factors. We postulated that these limitations could be partly overcome by primary stenting of the responsible lesion. MATERIAL AND METHODS: Since January/94 we have studied 59 patients with acute myocardial infarction who were treated in the early phase (3.1 +/- 2 hours since the onset of symptoms) by elective Palmaz-Schatz stent implantation. No adjunctive thrombolytic therapy was associated. Two patients were in cardiogenic shock and were treated under percutaneous cardiopulmonary support. At cardiac catheterization a left ventriculography and coronary angiograms were obtained. Then, mechanical recanalization of the responsible lesion was performed. If the angiographic anatomy was considered suitable, a stent was implanted at the lesion. RESULTS: The infarct related artery was the left anterior descending in 29 patients, the circumflex in 14 and the right coronary artery in 16. At baseline conditions, 40 patients had a totally occluded artery and 19 showed a TIMI-grande 1 antegrade flow. One patient had an early clinical recurrence 4 days later, which required an additional divided Palmaz-Schatz stent at the distal portion of the lesion, in order to seal a residual dissection. All remaining patients had a favourable clinical course without major complications. Immediately after treatment the minimal lumen diameter was 3.2 +/- 0.4 mm and no residual stenosis was detectable at the treated segment. Six-month angiographic reevaluation was performed in all 29 (49%) eligible patients. Restenosis (> 50% stenosis) was detected in 6 out of the 29 evaluated patients (21%). CONCLUSIONS: Primary stent implantation in selected patients with an evolving myocardial infarction provides good initial and 6-month results.

Acute Disease↗
PubMed1997

[Detection of t(15;17) using cytogenetic, fluorescent in situ hybridization, and molecular techniques. Comparative study of 11 patients with acute promyelocytic leukemia].

OBJECTIVES: Analysis and comparison of the sensitivity for the detection of t(15; 17) with conventional cytogenetic (CC), Southern blotting (SB), metaphase fluorescence in situ hybridization (M-FISH), interphase fluorescence in situ hybridization (I-FISH) and polymerase chain reaction (PCR) techniques. PATIENTS AND METHODS: 11 acute promyelocytic leukaemia (APL) patients (9 M3 and 2 M3v) were studied at diagnosis and partial remission and analyzed with CC (11 cases), SB (7 cases), I-FISH (2 cases) and PCR (3 cases) techniques. RESULTS: The percentages of detection of t(15;17) were: 90.9% (CC), 71.4% (SB), 85.7% (M-FISH) and 100% (I-FISH and PCR). Additional chromosomal abnormalities were detected in 2 cases with CC techniques. CONCLUSIONS: 1.- There is a very good correlation in the detection of t(15; 17) between the techniques analyzed. 2.- At diagnosis, partial remission and relapse, M-FISH and PCR provide a reliable diagnosis of t(15; 17). Nevertheless, it is important to perform a CC analysis because it enables the recognition of additional chromosome abnormalities with putative prognostic importance. 3.- At complete remission, I-FISH and PCR provide a rapid and safe screening of putative residual cells. 4.- The great sensibility of the techniques available for the detection of t(15; 17) translocation allows the use in each laboratory of the most appropriate techniques according to their substructure and the patients' clinical stage.

Chromosomes, Human, Pair 15↗