Cytogenetic analysis of 100 consecutive newly diagnosed cases of acute lymphoblastic leukemia in Rio de Janeiro

We report the cytogenetic analysis of newly diagnosed Brazilian children with acute lymphocytic leukemia (ALL). We investigated 100 ALL cases from four different institutions in Rio de Janeiro. The frequency of chromosomal abnormalities was 92.3%. The karyotype profile and recurrent abnormalities found in this study do not differ essentially from those described by other groups. Although the Brazilian population is usually the product of different ethnic groups, our results show that the frequency of each recurrent abnormality is similar to that found in populations without our degree of diverse ethnic composition. Hence, our results suggest that childhood ALL in Brazil has the same biological features as that in developed countries, supporting the use of similar treatment protocols. We can therefore expect to reach the same survival rates in the coming years, depending possibly on the efficacy of the support therapy and extent of social assistance.     

Most HIV type 1 non-B infections in the Spanish cohort of antiretroviral treatment-naïve HIV-infected patients (CoRIS) are due to recombinant viruses

HIV-1 group M is classified into 9 subtypes, as well as recombinants favored by coinfection and superinfection events with different variants. Although HIV-1 subtype B is predominant in Europe, intersubtype recombinants are increasing in prevalence and complexity. In this study, phylogenetic analyses of pol sequences were performed to detect the HIV-1 circulating and unique recombinant forms (CRFs and URFs, respectively) in a Spanish cohort of antiretroviral treatment-naïve HIV-infected patients included in the Research Network on HIV/AIDS (CoRIS). Bootscanning and other methods were used to define complex recombinants not assigned to any subtype or CRF. A total of 670 available HIV-1 pol sequences from different patients were collected, of which 588 (87.8%) were assigned to HIV-1 subtype B and 82 (12.2%) to HIV-1 non-B variants. Recombinants caused the majority (71.9%) of HIV-1 non-B infections and were found in 8.8% of CoRIS patients. Eleven URFs (accounting for 13.4% of HIV-1 non-B infections), presenting complex mosaic patterns, were detected. Among them, 10 harbored subtype B fragments. Four of the 11 URFs were found in Spanish natives. A cluster of three B/CRF02_AG recombinants was detected. We conclude that complex variants, including unique recombinant forms, are being introduced into Spain through both immigrants and natives. An increase in the frequency of mosaic viruses, reflecting the increasing heterogeneity of the HIV epidemic in our country, is expected.     

Evolution, antimicrobial susceptibility and assignment to international clones of methicillin-resistant Staphylococcus aureus isolated over a 9-year period in two Spanish hospitals

Antimicrobial resistance profiles, restriction fragment length polymorphism of the coagulase gene and repetitive element sequence-based PCR were used to classify 210 methicillin-resistant Staphylococcus aureus isolates recovered between 1997 and 2005 in two hospitals in Vigo, north-west Spain. Representative isolates belonging to the epidemic clones were analysed by spa typing and multilocus sequence typing, and the staphylococcal chromosomal cassette (SCC)mec type was determined for all isolates. The New York/Japan clone (t002-ST5-II) was detected in Spain for the first time. However, the New York/Japan and the Brazilian (t037-ST239-IIIA) clones were replaced by EMRSA-16 (t018-ST36-II), which at present is the predominant clone.     

Identification of a homologue of CD59 in a cyclostome: implications for the evolutionary development of the complement system

We have employed a COS cell expression cloning procedure to isolate a full length cDNA clone encoding a hagfish leukocyte-associated membrane protein (HLMP1). The protein, which is identified by a monoclonal antibody (JB3) generated in our laboratory, is present on the majority of hagfish leukocytes and is also expressed on erythrocytes. The cDNA clone contained an open reading frame encoding a 120 residue polypeptide which exhibits 33% amino acid sequence identity with the precursor protein of human CD59, a leukocyte-associated membrane protein which regulates the action of the complement membrane attack complex on homologous cells. CD59 belongs to a family of structurally related glycoproteins which includes the Ly-6 proteins expressed on mouse lymphocytes. In addition to significant overall sequence homology HLMP1 shows conservation of 8 key cysteine residues with members of the CD59/Ly-6 family. Comparison of the hagfish sequence with that of the mature human CD59 protein suggested a processed protein consisting of 74 amino acids associated with the cell membrane via a GPI anchor. The latter was confirmed by immuno-flow cytometry following treatment of transfected COS cells with phospholipase. Phylogenetic analysis and tissue distribution of this protein in the hagfish are consistent with HLMP1 being a homologue of CD59. A three-dimensional model of HLMP1, constructed using the NMR-determined structure for human CD59 as a template, indicated conservation of a core structure of five strands of beta-sheet and a short helix stabilised by four disulfide bonds. These findings, when taken together with our previous identification of C5a-like chemotactic activity in LPS-activated serum, provide indirect evidence for the existence of the terminal lytic complement pathway (C5 to C9) in these primitive vertebrates.     

Intrinsic <Emphasis Type="Italic">MYH7</Emphasis> expression regulation contributes to tissue level allelic imbalance in hypertrophic cardiomyopathy

HCM, the most common inherited cardiac disease, is mainly caused by mutations in sarcomeric genes. More than a third of the patients are heterozygous for mutations in the MYH7 gene encoding for the β-myosin heavy chain. In HCM-patients, expression of the mutant and the wildtype allele can be unequal, thus leading to fractions of mutant and wildtype mRNA and protein which deviate from 1:1. This so-called allelic imbalance was detected in whole tissue samples but also in individual cells. There is evidence that the severity of HCM not only depends on the functional effect of the mutation itself, but also on the fraction of mutant protein in the myocardial tissue. Allelic imbalance has been shown to occur in a broad range of genes. Therefore, we aimed to examine whether the MYH7-alleles are intrinsically expressed imbalanced or whether the allelic imbalance is solely associated with the disease. We compared the expression of MYH7-alleles in non-HCM donors and in HCM-patients with different MYH7-missense mutations. In the HCM-patients, we identified imbalanced as well as equal expression of both alleles. Also at the protein level, allelic imbalance was determined. Most interestingly, we also discovered allelic imbalance and balance in non-HCM donors. Our findings therefore strongly indicate that apart from mutation-specific mechanisms, also non-HCM associated allelic-mRNA expression regulation may account for the allelic imbalance of the MYH7 gene in HCM-patients. Since the relative amount of mutant mRNA and protein or the extent of allelic imbalance has been associated with the severity of HCM, individual analysis of the MYH7-allelic expression may provide valuable information for the prognosis of each patient.     

Dental age estimation in Spanish and Venezuelan children. Comparison of Demirjian and Chaillet’s scores

Orthopantomographs taken from 308 Spanish Caucasian and 200 Venezuelan Amerindian children, aged between 2 and 18 years, were analysed following the Demirjian’s method. The aims of this study were to test the applicability of the Demirjian’s method to two different sample populations, and to develop age prediction models for both populations using the original French Canadian scores described by Demirjian (1976) and the new multi-ethnic dental scores proposed by Chaillet et al. (2005) when the ethnic origin is unknown. Results showed that despite the good correlation between dental and chronological age, Demirjian’s method overestimates the age in the Spanish Caucasian sample using both scores, the mean overestimation being higher when the Demirjian’s scores were used than when the Chaillet’s scale was applied. In the Venezuelan Amerindian sample, the opposite was found: Demirjian’s method underestimates the age using both scores, the underestimation being higher when the Chaillet’s scale was applied than when Demirjian’s scale was used. New graphs were produced to convert the maturity scores to dental age for Spanish and Venezuelan children. With these graphs, the Demirjian’s scores showed to be inadequate after the age of 12 in both populations, while Chaillet’s scores offered useful information until 14 years of age.     

Linguistic and psychometric validation of the Erection Hardness Score to Spanish

IntroductionThe Erection Hardness Score (EHS) is a one‐item questionnaire that assesses rigidity on a 4‐point scale.AimTo perform a validation of a Spanish version of the EHS by comparison with the International Index of Erectile Function (IIEF) questionnaire.MethodsValidation of the EHS included: (i) professional translation of the scale; (ii) scientific evaluation of the translation from four independent urologists; (iii) assessment on five individuals to test correct comprehension and idiomatic adequacy (iv) validation of the EHS by a cross‐sectional, multicenter comparison with the IIEF.Main Outcome MethodsPatients were required to respond to a Spanish version of the EHS and IIEF. Statistic correlation was carried out between the EHS score and IIEF‐erectile function domain (EF) score.ResultsA total of 125 patients were recruited. Overall prevalence of erectile dysfunction (ED) by the EHS questionnaire was of 80.2% patients (n = 97). Mean EHS was 2.74 ± 0.97. Mean IIEF‐EF score was 17.4 ± 9.5. The EHS showed good reliability. The rate of missing responses to the EHS questionnaire was 0%. A one‐factor analysis of variance was performed between the EHS and EF subdomain of IIEF (P = 0.000). Pearson's correlation coefficient between EHS and EF subdomain of IIEF was 0.834, P < 0.01.ConclusionsThe EHS is a reliable tool to test ED and its Spanish version was satisfactorily understood by patients and correlated with IIEF‐EF. García‐Cruz E, Romero Otero J, Martínez Salamanca JI, Leibar Tamayo A, Rodríguez Antolín A, Astobieta Odriozola A, and Alcaraz A. Linguistic and psychometric validation of erection hardness score to Spanish. J Sex Med 2011;8:470–474.     

Translocation (11;11)(p13- p15;q23) in a child with therapy-related acute myeloid leukemia following chemotherapy with DNA-topoisomerase II inhibitors for Langerhans cell histiocytosis

We report a new case of therapy-related acute myeloid leukemia in a child with Langerhans cell histiocytosis. This patient was previously treated with a protocol of multidrug chemotherapy, containing a relatively low dose of etoposide (total dose of 900/m(2)). Twenty-six months after the end of the therapy, the patient returned to the hospital with fever and anemia. The white blood cell count was 53 x 10(9)/L. The bone marrow examination showed massive infiltration with French-American-British acute myeloid leukemia classification M4 blast cells. The patient did not respond to an intensive treatment with high dose ARA-C and idarubicin. He died 6 months later. The cytogenetic abnormality of the blast cells was a t(11;11)(p13 -15;q23), that has not been described before in a secondary leukemia case.