RESUMO
Fanconi anaemia (FA) is a genetically heterogeneous autosomal recessive disorder associated with chromosomal fragility, bone-marrow failure, congenital abnormalities and cancer. The gene for complementation group A (FAA), which accounts for 60-65% of all cases, has been cloned, and is composed of an open reading frame of 4.3 kb, which is distributed among 43 exons. We have investigated the molecular pathology of FA by screening the FAA gene for mutations in a panel of 90 patients identified by the European FA research group, EUFAR. A highly heterogeneous spectrum of mutations was identified, with 31 different mutations being detected in 34 patients. The mutations were scattered throughout the gene, and most are likely to result in the absence of the FAA protein. A surprisingly high frequency of intragenic deletions was detected, which removed between 1 and 30 exons from the gene. Most microdeletions and insertions occurred at homopolymeric tracts or direct repeats within the coding sequence. These features have not been observed in the other FA gene which has been cloned to date (FAC) and may be indicative of a higher mutation rate in FAA. This would explain why FA group A is much more common than the other complementation groups. The heterogeneity of the mutation spectrum and the frequency of intragenic deletions present a considerable challenge for the molecular diagnosis of FA. A scan of the entire coding sequence of the FAA gene may be required to detect the causative mutations, and scanning protocols will have to include methods which will detect the deletions in compound heterozygotes.
Assuntos
Anemia de Fanconi/genética , Mutação , Sequência de Bases , Primers do DNA , Éxons , Anemia de Fanconi/etnologia , Teste de Complementação Genética , Heterozigoto , HumanosRESUMO
Results of cytogenetic studies, performed in a group of 201 institutionalized mentally retarded males, are presented. At least two cytogenetic methods for eliciting the Xq27.3 fragile site, recommended by the Fourth International Workshop on the Fra X Syndrome were used. A subgroup of 67 out of 201 studied males was also examined using molecular methods. In 6 (2.9%) males fra X syndrome was diagnosed. All cytogenetic positive results were confirmed by molecular analysis. Five patients had full expansion CGG repeats and one had both premutation and full mutation. Postulated frequency of fra X syndrome in Polish population being 0.2-0.4/1,000 males seems to be lower than it could be expected on the basis of previous literature data.
Assuntos
Síndrome do Cromossomo X Frágil/epidemiologia , Deficiência Intelectual/genética , Síndrome do Cromossomo X Frágil/genética , Humanos , Institucionalização , Masculino , Mutação , Polônia/epidemiologia , Prevalência , Repetições de TrinucleotídeosRESUMO
Seventy-eight patients: 45 children, 33 adults and 27 normal healthy donors were enrolled in the study. Expression of P-glycoprotein (P-gp) was evaluated with three monoclonal antibodies (MAb's) directed to intra-(C219, JSB-1) and extra-cellular (MRK-16) epitopes of P-gp and immunocytochemical (IC) APAAP staining method. Twenty-seven healthy donors peripheral blood mononuclear cells (PBMC) were investigated by means of IC and FACScan analysis. Positive staining for P-gp was detected in 31% children's and 33% adults' leukemia samples. No reactivity of three MAb's was observed with peripheral blood mononuclear cells (PBMC) by means of IC. Flow cytometry analysis with C219 MAb revealed staining for P-gp present on sub-population of lymphocytes and monocytes. P-gp (+) as well as P-gp (-) cases were compared in respect to clinical outcome, FAB classification and blood group. Complete remission (CR) was achieved in 12/14 (85%) children's and 9/11 (81%) adults' P-gp (+) leukemia cases. Within the P-gp (-) leukemia cases CR was observed in 24/29 (82%) and 18/22 (81%), respectively. Partial remission, relapse, resistance and death were noticed in 14% children's and 18% adults' P-gp (+) samples. In P-gp (-) cases these parameters were observed in 17% and 18%, respectively. These results raise the question whether the expression of P-gp can be used as single prognostic marker to detect multidrug resistance (MDR phenomenon) in vivo?
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/análise , Resistência a Múltiplos Medicamentos , Leucemia Mieloide Aguda/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Adulto , Anticorpos Monoclonais , Biomarcadores , Crise Blástica , Linhagem Celular , Criança , Epitopos/análise , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica/métodos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/imunologia , Linfócitos/patologia , Linfoma não Hodgkin/sangue , Linfoma não Hodgkin/imunologia , Linfoma não Hodgkin/patologia , Masculino , Monócitos/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Resultado do Tratamento , Células Tumorais CultivadasRESUMO
The most common hematological abnormality associated with HIV infection is anaemia. The aetiology is multifactorial and may include the HIV virus itself; the anaemia of chronic diseases (ACD); infection with other viruses, mycobacteria and fungi; medications, especially zidovudine; and even B12 deficiency. Erythropoietin insufficiency is present in all anaemic AIDS patients, probably as a result of the mechanism of ACD. The studies, performed in patients with PGL, ARC and AIDS stages of disease demonstrate that rHuEPO is safe, and in dose of 100-200 U/kg b.w. three times a week can alleviate the anemia in AIDS patients taking AZT whose baseline EPO levels are less than 500 mU/ml.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Anemia/tratamento farmacológico , Anemia/etiologia , Eritropoetina/deficiência , Eritropoetina/uso terapêutico , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Doença Crônica , Eritropoetina/metabolismo , Humanos , Zidovudina/farmacologia , Zidovudina/uso terapêuticoRESUMO
The authors evaluated results of treatment of 106 children with acquired aplastic anemia. The patients were divided into 3 groups depending on the severity of their disease. Thirty-nine patients were classified as very severe, 30 as severe and 37 as non-severe according to the modified Camitta criteria. Among them, 47 children were treated with oxymetholone and prednisolone. In this group 32 died. Antilymphocyte globulin (ALG) was given to 48 patients and 20 received cyclosporin A (CsA). The results obtained by these two methods are nearly the same and 5 year survival was 61% and 59% respectively. Bone marrow was transplanted in only one child, who is still in complete remission. Statistical analysis showed a steady increase in incidence of aplastic anemia in the years 1987-1989, which might coincide with the Czarnobyl explosion. However, further research is required to prove this point.
Assuntos
Anemia Aplástica/terapia , Adolescente , Anemia Aplástica/classificação , Anemia Aplástica/epidemiologia , Anemia Aplástica/mortalidade , Soro Antilinfocitário/uso terapêutico , Transplante de Medula Óssea , Criança , Pré-Escolar , Ciclosporina/uso terapêutico , Feminino , Humanos , Incidência , Lactente , Masculino , Oximetolona/uso terapêutico , Polônia/epidemiologia , Prednisolona/uso terapêutico , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do TratamentoAssuntos
Agranulocitose/imunologia , Antineoplásicos/efeitos adversos , Infecções Bacterianas/etiologia , Leucemia Mieloide Aguda/tratamento farmacológico , Infecções Oportunistas/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Agranulocitose/induzido quimicamente , Antineoplásicos/uso terapêutico , Criança , Humanos , Tolerância Imunológica/efeitos dos fármacos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologiaRESUMO
A group of 30 patients clinically described as having the Prader-Willi Syndrome (PWS) were studied using microsatellites from 15q11-13 and methylation analysis with probe PW71B (D15S63). The patients were categorized according to clinical symptoms. 80% of all patients were informative using molecular and cytogenetic methods. Among 8 patients with an atypical PWS phenotype, 2 showed uniparental disomy, and 2 had a mosaic deletion for 15q. The last 4 atypical and 2 typical patients had neither molecular defects confirmed by microsatellite analysis nor a parent-of-origin-specific methylation pattern for PWS. Our results confirm that methylation pattern analysis provides an additional and alternative microsatellite analysis to diagnose PWS.