Expression of TLR2 and TLR4 in lesions of patients with tegumentary american leishmaniasis / Expressão de TLR2 e TLR4 em lesões de pacientes com leishmaniose tegumentar americana

OBJECTIVES: The aim of this study was to describe the pattern of expression of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) in skin biopsies of patients with American tegumentary leishmaniasis (ATL) caused by Leishmania braziliensis. METHODS: This prospective study evaluated 12 patients with ATL caused by Leishmania braziliensis confirmed by polymerase chain reaction. Immunohistochemistry was performed to determine the expression of TLR2 and TLR4. The number of NK cells, dendritic cells and macrophages in the tissue were calculated. The cytokine expression was determined using the anti-TNF-α, anti-IFN-Γ, anti-IL-1 and anti-IL-6. Double immunostaining reactions were used to determine the cell expressing TLR2 and TLR4. RESULTS: The numbers of cells expressing TLR2 and TLR4 were 145.48 ± 82.46 cell/mm² and 3.26 ± 4.11 cell/mm² respectively (p < 0.05). There was no correlation of TLR2 and TLR4 with the amount of cytokines and the number of NK cells, dendritic cells or macrophages. The double immunostaining revealed that TLR2 was expressed by macrophages. CONCLUSION: In human cutaneous leishmaniasis caused by Leishmania braziliensis, TLR2 is the most common TLR expressed during active disease, mainly by macrophages although without correlation with the amount of cytokines and number of cells.

OBJETIVOS: O objetivo deste estudo foi descrever o padrão de expressão dos receptores toll-like 2 e 4 (TLR2 e TLR4) em biópsias de pele de pacientes com leishmaniose tegumentar americana (LTA). MÉTODOS: Este estudo prospectivo avaliou 12 pacientes com LTA causada por Leishmania braziliensis confirmada por reação em cadeia da polimerase. Imunohistoquímica foi realizada para determinar a expressão de TLR2 e TLR4. O número de células NK, células dendríticas e macrófagos foi calculado no tecido. A expressão de citocinas foi determinada usando anti-TNF-α, anti-IFN-Γ, anti-IL-1 e anti-IL-6. Dupla marcação foi usada para determinar a célula responsável pela expressão de TLR2 e TLR4. RESULTADOS: O número de células expressando TLR2 e TLR4 foi 145.48±82.46 cell/mm² e 3.26 ± 4.11 cell/mm² respectivamente (p < 0.05). Não houve correlação entre a quantidade de expressão de TLR2 e TLR4 com a quantidade de citocinas e o número de células NK, macrófagos e células dendríticas. A dupla marcação revelou que o TLR2 é expresso por macrófagos. CONCLUSÃO: Na LTA causada por Leishmania braziliensis, TLR2 é o TLR mais comum na doença ativa, principalmente por macrófagos sem correlação com a quantidade de citocinas e outras células.

In acute lymphoblastic leukemia deletion of the tumor suppressor gene P16 is associated with abnormal interferon genes

The putative tumor-suppressor gene p16 was mapped to human chromosome 9p21, close to the interferon alpha cluster. The frequency and association of gene alterations of p16, interferon alpha and interferon beta were investigated in a total of 39 Acute Lymphoblastic Leukemia (ALL) patients. Of these, 10 patients (25.6 per cent) presented abnormalities of at least one of the three genes studied. In 32 ALL cases studies of the three genes could be accomplished. In 23 out of 32 ALL cases the 3 genes studied were normally preserved. In the remaining 9 ALL, p16 was affected in 8 cases by homozygous deletions. In 2 patients, p16 deletion was associated with homozygous deletions for interferon alpha and interferon beta genes and in 1 case with total deletion of interferon beta 1 gene and partial deletion of interferon alpha. In the remaining 5 cases, p16 was the only gene deleted with no alteration of type interferon genes. These data indicate that p16 gene is deleted in a higher frequency than type I interferon genes in ALL. Moreover, within the ALL group with p16 gene deletion, 37.5 per cent are associated with interferon deletions and in general, ALL with alpha and/or beta interferon gene deletions are associated with p16 deletions. Therefore, p16 gene deletion with preserved type I interferon genes in some ALL suggests that the absence of this cdk inhibitor may disturb the normal cell cycle and favor blast transformation.

Bases para el uso combinado de los interferones y de los retinoides en oncología clínica / Basis for the combined use of interferon and retinoid in clinical oncology

El acido retinoico y el interferón alfa tienen actividad limitada en el tratamiento de cáncer avanzado. La información obtenida de los cultivos celulares indican que, en combinación, estos agentes tienen incremento de la actividad biológica modulando el crecimiento y la diferenciación en un número de tipos celulares malignos. Trabajos clínicos recientes sobre el tratamiento de algunos carcinomas avanzados de células escamosas informan actividad terapéutica con este régimen. Este artículo revisa los datos preclínicos obtenidos al evaluar el ácido retinoico en combinación con interferones

Caracterización química del interferón humano alfa-2 recombinante / Chemical characterization of human alpha-2 recombinant interferon

El interferón humano alfa-2 recombinante con alto grado de pureza, expresado en E. coli, fue analizado con vistas a verificar su secuencia aminoacídico. El análisis de aminoácidos permitió comprobar que el contenido aminoacídico de la molécula es correcto. Mediante estudios de cromatografía líquida de alta eficacia se evaluó la pureza de la proteína. Se obtuvieron los mapas peptídicos con diferentes proteasas y métodos químicos, aislándose de una de estas digestiones los péptidos trípticos para su secuencia automática. Se determinó que una parte del material se inicia en metionina y otra en cisteína. La secuencia aminoacídica de la proteína se verificó, coincidiendo esta con la secuencia predicha a partir de la secuencia del gen clonado. Se estableció la secuencia C-terminal mediante análisis enzimático