Biomedical subjects
Publications and source records attributed to P Cabello.
We report a case of primary thrombocythaemia showing a translocation t(4; 6)(q21; q27) five years after diagnosis. The patient had been treated with hydroxyurea. The clinical picture at the time was consistent with transformation. Karyotypic abnormalities are rare in this disease and are reviewed.
BACKGROUND AND OBJECTIVES: The detection of PML-RAR by reverse transcription (RT) polymerase chain reaction (PCR) in acute promyelocytic leukemia (APL) patients who are in hematologic remission influences therapeutic decision making in several trials. In the light of this, the Spanish group has recently designed an external quality assessment program (EQAP) of RT-PCR detection of PML-RAR, which includes a study of sensitivity of the participating laboratories. DESIGN AND METHODS: Eighteen laboratories were involved in the program. Ten laboratories followed the method of Biondi et al., 5 employed that of Borrow et al. and the 3 remaining used other protocols. The sensitivity was studied in five rounds of quality control. The first two shipments consisted of dilutions of NB4 RNA into non-APL RNA. The third round consisted of serial dilutions of the NB4 cell line into HL60 cells. The fourth and five rounds consisted of plasmid dilutions containing the bcr1 and bcr3 PML-RAR isoforms. RESULTS: The results showed that the distinct methods allow detection of the PML-RAR hybrid up to a dilution of 10(-4), and exceptionally, up to 10(-5). The laboratories following the method of Biondi et al. usually detected the 10(-3) dilution and less frequently the 10(-4) one, whereas those using other methods usually detected PML-RAR transcript in the 10(-4) dilution, and less commonly in the 10(-5) dilution. However, each of the PCR methods used by EQAP participating laboratories successfully detected at least 50 copies of PML-RAR alpha fusion transcript in plasmid dilution controls. INTERPRETATION AND CONCLUSIONS: The results point to heterogeneous sensitivity amongst participating laboratories. This may reflect differences in methodology, although variations in sample quality may also account for discrepant findings.
Malignant transformation of human cells requires the accumulation of multiple genetic alterations, such as the activation of oncogenes and loss of function of tumor suppressor genes or those related to genomic instability. Among the genetic alterations most frequently found in human tumors are chromosomal translocations that may result in the expression of chimeric products with transforming capability or are able to change the expression of oncogenes. We show here that the adenovirus early region 1A (E1A) gene can induce a specific human fusion transcript (EWS-FLI1) that is characteristic of Ewing tumors. This fusion transcript was detected by RT-PCR in normal human fibroblasts and keratinocytes after expression of the adenovirus E1A gene, as well as in human cell lines immortalized by adenoviruses. Cloning and sequencing of the RT-PCR product showed fusion points between EWS and FLI1 cDNA identical to those detected in Ewing tumors. In addition, we detected a chimeric protein by western blot analysis and immunoprecipitation and a t(11,22) by fluorescent in situ hybridization. This association between a single viral gene and a specific human fusion transcript indicates a direct link between viral genes and chromosome translocations, one of the hallmarks of many human tumors.
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BACKGROUND: Hemochromatosis is a hereditary disease the diagnosis and early therapy of which is particularly relevant to prevent the appearance of complications. In 1996, the gene responsible for this condition was identified and was named HFE. OBJECTIVE: To determine the prevalence of Cys282Tyr (C282Y) and His63Asp (H63D) mutations in the HFE gene in a group of patients with the confirmed diagnosis of hereditary hemochromatosis, as well as in a control group of 174 healthy individuals. MATERIALS AND METHODS: Twenty-two patients with the diagnosis of primary hemochromatosis who were on treatment with periodic phlebotomies were studied. All patients had the following parameters measured: serum iron, ferritin, transferrin saturation, serology for hepatitis viruses B and C, liver function tests, abdominal echography and liver biopsy. A control group of 174 healthy individuals, who had their serotype analyzed, was also studied. RESULTS: Eighteen (81.8%) of patients with hemochromatosis were homozygous for the C282Y mutation. One patient was homozygous for the H63D mutation and in other patient no mutation was found. Among individuals in the control group, the allelic frequency of the C282Y mutation was 2.3%, whereas the allelic frequency of the H63D mutation was 19.8%. CONCLUSIONS: The results obtained in our study support the evident association between the C282Y mutation in the HFE gene and hereditary hemochromatosis in our environment.
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The effects of the non-competitive antagonists of the glutamate complex receptor, dizocilpine (MK 801) and ketamine and of the competitive antagonist CGP 39551 were examined on the induction of tolerance to morphine, the development of physical dependence and the expression of the abstinence syndrome to the opiate in mice. Morphine was administered in a single dose (300 mg/kg) of a slow release preparation. Dizocilpine (0.005 or 0.01 mg/kg given at 3, 12 and 24 h after the priming dose of morphine), ketamine (2, 4 or 8 mg/kg, 30 min before and 3, 6, 9 and 24 h after the priming dose) and DL-(E)-2-amino-4-methyl-5-phosphonopentanoate carboxy-ethylester (CGP 39551) (1.5 or 3 mg/kg, but not 6 or 12 mg/kg 30 min before and 12 and 24 h after the priming dose) reduced the intensity of tolerance to, and physical dependence on morphine. The drugs also reduced the intensity of the abstinence behaviour when given in a single dose, 30 min before (s.c.) naloxone (4 mg/kg)-precipitated withdrawal syndrome in mice chronically treated with morphine. Thus, the results of this study indicate that competitive and non-competitive NMDA receptor antagonists prevent morphine tolerance and decrease the development of physical dependence on the opiate in mice.
We describe the cytogenetic study of a neuroendocrine tumor of Merkel cells which appeared in a patient following a heart transplant. An abnormal karyotype was observed in a metastatic lymph node. The abnormality includes two markers derived from the long arm of chromosome 1, while maintaining two normal chromosomes 1.
The origin of a de novo metacentric small marker chromosome found in a cytogenetic study in amniotic fluid was determined by fluorescence in situ hybridization (FISH) using chromosome specific probes. It was identified as an isochromosome 18p. We want to emphasize that when an extra chromosome is found in prenatal diagnosis and it cannot be identified by conventional cytogenetics banding, FISH should be applied in order to give real risks for fetal anomalies and an accurate genetic counselling.
A 51-year-old male patient was diagnosed with Burkitt lymphoma 3 months after cardiac transplantation. The bone marrow karyotype was very complex, and to better define the complex karyotype we used the in situ suppression hybridization technique. Previously we interpreted this karyotype to be: 48,XY,t(2;8)(p11;q24), +der(2)t(2;8)(p11;q24),del(2)(q23), +7, +der(8)t(2;8)(p11;q24), +12, -13, -18, by G banding techniques, with a duplication of the t(2;8) derivatives. After in situ hybridization we changed to a: 48,XY,t(2;8)(p11;q24),t(2;18)(q23;q22), +7, +der(8)t(2;8)(p11;q24), +12, -13, which implies duplication of only one t(2;8) derivative.
We report a patient with chronic myelocytic leukaemia (CML) in blastic crisis with a del (7) (p11 p15) in addition to the Philadelphia chromosome. A potential relationship between the presence of this deletion and the therapy in chronic phase is suggested.
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We report a case of acute myeloid leukemia (M5a of the FAB classification), secondary to the myelodysplastic syndrome, showing a deletion of the short arm of chromosome 2 at p23 in the bone marrow cells. In addition, a duplication of chromosome 13,dup(13)(q12q14) was found.
The introduction of molecular biological techniques in the study of chronic myeloid leukaemia (CML) allows us to show the bcr/abl gene rearrangement produced by the translocation between the c-abl proto-oncogene located in chromosome 9 and the bcr region located in chromosome 22, which constitutes the molecular alteration of Philadelphia chromosome in CML. We present the usefulness of the bcr/abl gene rearrangement study in the diagnosis of a blast crisis initially located in lymph nodes of a patient with CML. The DNA analysis allows demonstration that the lymph node neoplastic cells originate from the clone responsible for the CML, while obtaining metaphases from a lymph node for the cytogenetic study gives rise to enormous difficulties and is practically impossible if the problem is studied retrospectively based on frozen or fixed samples.
In situ hybridization was used to characterize an undetected chromosome translocation in a child whose metaphase chromosome analysis in peripheral blood and in skin culture revealed apparent monosomy 21. The cytogenetic study revealed 45 chromosomes, and no other structural anomalies were detected with G banding. In situ hybridization of chromosome 21-specific probes to metaphase chromosomes and reverse banding from the proband showed a de novo translocation between chromosome 5 and chromosome 21.
Forty vesical neoplasias in various stages and which were treated through transurethral resection followed by chemotherapy, in accordance to the currently accepted approach, were studied using transurethral ultrasound techniques. A histochemical correlation is established based on the proposed U.I.C.C. grading (T.N.M.). Such correlation coincides in 88.2% of cases for the "unified" Ta-T1 stage; 70% for T2; 88.8% for T3; and 100% for T4.
A patient diagnosed with chronic myeloid leukemia was studied periodically during his illness. The result showed the presence of a Philadelphia (Ph) chromosome by a 9;22 translocation as a single abnormality to the time of blastic crisis. At that time, the chromosome studies showed a clonal evolution. Furthermore, a second derivated line was added to the Ph line. This new anomaly consisted of a 8;21 translocation, considered as specific of M2 type acute nonlymphoblastic leukemia of French-American-British classification.