RESUMEN
We analyzed a group of 45 Brazilian individuals, 30 with acute myeloid leukemia (AML), 15 with acute lymphoid leukemia (ALL) and 100 healthy controls to assess genetic factor risk and HLA association contribution to the disease. Patient rates were compared with age and sex-matched control groups by directly typing the HLA-DRB1/3/4/5 and -DQB1 loci by PCR analysis. We observed significantly increased allelic distribution of HLA-DRB107 in AML patients and of HLA-DRB103 in ALL patients, which suggests that individuals in both groups are susceptible to the disease. We also found significantly decreased allelic distribution of HLA-DQB104 in AML patients and of HLA-DRB104 and -DQB103 in ALL patients, which suggests protection against the disease. We further found increased HLA-DRB107 and -DQB102 haplotypes in AML patients, which suggests susceptibility to the disease and decreased HLA-DRB104 and -DQB103 haplotypes in ALL patients, which also suggests protection against the disease. Future studies with larger and/or multicentric samples will be required for better comprehension of the HLA role in acute leukemia pathogenesis.
Asunto(s)
Antígenos HLA-DQ , Antígenos HLA-DR , Leucemia Linfoide/diagnóstico , Leucemia Mieloide Aguda/diagnóstico , Enfermedad Aguda , Adulto , Factores de Edad , Brasil , Femenino , Estudios de Seguimiento , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Antígenos HLA-DQ/genética , Cadenas beta de HLA-DQ , Antígenos HLA-DR/genética , Cadenas HLA-DRB1 , Haplotipos , Humanos , Leucemia Linfoide/genética , Leucemia Mieloide Aguda/genética , Masculino , Factores SexualesRESUMEN
CONTEXT AND OBJECTIVE: The technique of obtaining human skin with dermis and epidermis reconstructed from cells isolated from patients can enable autologous skin grafting on patients with few donor sites. It also enables in vitro trials on chemicals and drugs. The objective of this work was to demonstrate a method for obtaining human skin composed of associated dermis and epidermis, reconstructed in vitro. DESIGN AND SETTING: Experimental laboratory study, in the Skin Cell Culture Laboratory of Faculdade de Ciências Médicas, Universidade Estadual de Campinas. METHODS: Cells from human fibroblast cultures are injected into bovine collagen type I matrix and kept immersed in specific culturing medium for fibroblasts. This enables human dermis reconstruction in vitro. On this, by culturing human keratinocytes and melanocytes, differentiated epidermis is formed, leading to the creation of human skin composed of associated dermis and epidermis, reconstructed in vitro. RESULTS: We showed that human skin composed of associated dermis and epidermis can be successfully reconstructed in vitro. It is histologically formed in the same way as human skin in vivo. Collagen tissue can be identified in the dermis, with cells and extracellular matrix organized in parallel to multilayer epidermis. CONCLUSIONS: It is possible to obtain completely differentiated human skin composed of associated dermis and epidermis, reconstructed in vitro, from injection of human fibroblasts into bovine collagen type I matrix and culturing of human keratinocytes and melanocytes on this matrix.
Asunto(s)
Dermis/citología , Células Epidérmicas , Fibroblastos/citología , Ingeniería de Tejidos/métodos , Animales , Bovinos , Colágeno Tipo I , Matriz Extracelular , Humanos , Inmunohistoquímica , Queratinocitos/citología , Melanocitos/citologíaRESUMEN
CONTEXTO E OBJETIVO: A técnica para obtenção de pele humana que apresente derme e epiderme, reconstruída a partir de células isoladas de pacientes, pode possibilitar a realização de enxertos autólogos de pele reconstruída em laboratório em pacientes com áreas doadoras escassas, além de permitir ensaios com substâncias químicas e drogas in vitro e não mais in vivo. O objetivo do trabalho é demonstrar um método de obtenção de pele humana reconstruída in vitro composta de derme e epiderme associadas. TIPO DE ESTUDO E LOCAL: Estudo experimental laboratorial realizado no Laboratório de Cultura de Células da Pele da Faculdade de Ciências Médicas da Universidade Estadual de Campinas, Campinas, São Paulo, Brasil. MÉTODOS: A partir da cultura de fibroblastos humanos, é possível obter um número suficiente de células que podem ser injetadas em uma matriz de colágeno bovino tipo I que, mantida imersa em meio de cultura específico para fibroblastos, permite a formação de uma derme humana reconstruída in vitro. Sobre essa derme, por meio de cultura de queratinócitos e melanócitos humanos, forma-se epiderme diferenciada, levando à formação de pele humana reconstruída in vitro, composta de derme e epiderme associadas. RESULTADOS: Demonstramos que é possível reproduzir pele humana reconstruída in vitro, composta de derme e epiderme associadas. Essa pele humana formada é, histologicamente, semelhante à pele humana in vivo. Na derme, identifica-se o tecido colágeno, com suas células, e a matriz extracelular organizados paralelamente à epiderme. Esta se desenvolve em várias camadas. CONCLUSÃO: É possível obter pele humana reconstruída in vitro, completamente diferenciada, composta de derme e epiderme, associadas, a partir da injeção de fibroblastos humanos em uma matriz de colágeno bovino tipo I e da cultura seqüencial de queratinócitos e melanócitose humanos sobre essa matriz contendo fibroblastos em seu interior.
Asunto(s)
Humanos , Animales , Bovinos , Dermis/citología , Epidermis/citología , Fibroblastos/citología , Ingeniería de Tejidos/métodos , Colágeno Tipo I , Matriz Extracelular , Inmunohistoquímica , Queratinocitos/citología , Melanocitos/citologíaRESUMEN
We analyzed 100 control individuals and 60 patients with psoriasis vulgaris from the population of Campinas, Brazil. Typification of class II HLA alleles (HLA-DRB1-5 and -DQB1) was carried out through the DNA/PCR/SSP at medium and high resolution. DNA was extracted through a salting-out procedure: 13 DRB1 alleles, 3 DRB3 alleles, 1 DRB4 allele, 2 DRB5 alleles, and 5 DQB1 alleles were identified at a medium resolution using the PCR/SSP, and 45 DRB1 alleles were identified at a high resolution in analyzed patients. Results showed associations with psoriasis vulgaris: positive associations HLA-DRB3*02 (p < 0.05, chi(2) = 5.10, RR = 2.14); HLA-DRB1*0102 alleles (p < 0.05, RR = 5.44). Negative associations were found for HLA-DRB4*01 (chi(2) = 3.23, RR = 0.55) and HLA-DRB1*1302 alleles (p < 0.05, RR = 0.23). The haplotypes revealed positive association for HLA-DRB1*0102/DQB1*05 (p < 0.05, RR = 5.44) and HLA-DRB1*0701/DQB1*03 alleles (p < 0.02, RR = 9.00). These findings suggest a possible association of the DRB1 allele with the group of patients showing an early onset of the illness, as well as an association with haplotypes HLA-DRB1*0102/DQB1*05 and HLA-DRB1*0701/DQB1*03.