Leucemia aguda de fenotipo mixto: presentación de un caso pediátrico de Perú / Acute leukemia of mixed phenotype: presentation of a pediatric case from Peru

Introducción: Las leucemias agudas de linaje ambiguo representan un grupo heterogéneo de leucemias sin una clara diferenciación del linaje celular. Constituyen alrededor de 2 a 5 por ciento del total de leucemias agudas. Objetivo: Describir un caso de leucemia aguda de fenotipo mixto (LAFM) en un paciente pediátrico de 4 años de Lambayeque, Perú. Presentación del caso: Se evaluó una muestra de sangre periférica de un niño de 4 años de edad, cuyo inmunofenotipo por citometría de flujo evidenció una población, correspondiente al 94 por ciento de la celularidad total, de linajes mieloide compatible con diferenciación a linaje neutrófilo y en menor medida a monocítica/célula dendrítica (CD123 intenso), con expresión de mieloperoxidasa (MPO) y CD33 intensos; CD13, CD64 y CD66c parcial; y expresión de marcadores de linaje linfoide B (CD19 y CD22 intensos). Este fenotipo obliga a descartar la t(8;21), y anomalías del gen MLL. Por los mencionados hallazgos, la presente leucemia fue clasificada como leucemia aguda de fenotipo mixto, B/Mieloide. Conclusiones: Se concluyó como una leucemia aguda de fenotipo mixto B/Mieloide, con la peculiar inclinación del linaje mieloide hacia neutrófilos y en menor medida hacia monocítica/célula dendrítica(AU)

Introduction: Acute leukemias of ambiguous lineage represent a heterogeneous group of leukemias without a clear differentiation of the cell lineage. They constitute about 2 to 5 percent of all acute leukemias. Objective: To describe a case of acute leukemia of mixed phenotype (LAFM) in a 4-year-old pediatric patient from Lambayeque, Peru. Case presentation: A peripheral blood sample from a 4-year-old boy was evaluated, whose immunophenotype by flow cytometry showed a population, corresponding to 94 percent of total cellularity, of myeloid lineages compatible with differentiation to neutrophil lineage and in less to monocytic/dendritic cell (CD123 high), with expression of myeloperoxidase (MPO) and CD33 high; CD13, CD64 and CD66c partial; and expression of B lymphoid lineage markers (CD19 and CD22 high). This phenotype requires ruling out the t (8; 21), and abnormalities of the MLL gene. Due to the aforementioned findings, the present leukemia was classified as acute leukemia of mixed phenotype, B/Myeloid. Conclusions: It was concluded as an acute leukemia of mixed phenotype B/Myeloid, with the peculiar inclination of the myeloid lineage towards neutrophils and to a lesser extent towards monocytic/dendritic cell(AU)

Diagnóstico, clasificación y tratamiento de la leucemia aguda de linaje ambiguo / Diagnosis, classification and treatment of acute leukemia of ambiguous lineage

Introducción: Las leucemias agudas de linaje ambiguo constituyen un grupo heterogéneo de leucemias agudas que no muestran una evidencia clara de diferenciación a lo largo del linaje celular. El diagnóstico definitivo se realiza exclusivamente por las características inmunofenotípicas, con el uso de la citometría de flujo multiparamétrica. Objetivo: Actualizar los criterios diagnósticos, la clasificación, el manejo clínico y terapéutico de las leucemias agudas de linaje ambiguo. Métodos: Se realizó una búsqueda de información científica relacionada con el tema en libros de textos de Hematología Clínica y en artículos publicados a través de PUBMED en los últimos 10 años. Se hizo un análisis y resumen de la bibliografía revisada. Análisis y síntesis de la información: Las características morfológicas de las células leucémicas procedentes de los pacientes con leucemias agudas de linaje ambiguo no muestran uniformidad. Pueden encontrarse de forma simultánea blastos de diferentes tamaños y estados de maduración. Estos pueden presentar apariencia linfoide, mieloide, indiferenciada o mixta. Conclusión: Las leucemias agudas de linaje ambiguo constituyen un subgrupo de alto riesgo, con un pronóstico desfavorable y una pobre supervivencia global de los enfermos. Su reporte oportuno es indispensable para aunar los criterios de la toma de decisiones terapéuticas en este grupo de pacientes(AU)

Introduction: Acute leukemias of ambiguous lineage constitute a heterogeneous group of acute leukemias that do not show clear evidence of differentiation along cell lineage. The definitive diagnosis is made exclusively based on immunophenotypic characteristics, with the use of multiparametric flow cytometry. Objective: To update the diagnostic criteria, classification, as well as the clinical and therapeutic management of acute leukemias of ambiguous lineage. Methods: A search for scientific information related to the subject was carried out in clinical hematology textbooks and in articles published through PUBMED in the last ten years. An analysis and summary of the revised bibliography was carried out. Information analysis and synthesis: The morphological characteristics of the leukemic cells from patients with acute leukemia of ambiguous lineage do not show uniformity. Blasts of different sizes and stages of maturation can be found simultaneously. These may appear as lymphoid, myeloid, undifferentiated, or mixed. Conclusion: Acute leukemias of ambiguous lineage constitute a high-risk subgroup, with unfavorable prognosis and poor overall patient survival. Its timely report is essential to gather criteria for making therapeutic decisions in this group of patients(AU)

The consensus sequence of FAMLF alternative splice variants is overexpressed in undifferentiated hematopoietic cells

The familial acute myeloid leukemia related factor gene (FAMLF) was previously identified from a familial AML subtractive cDNA library and shown to undergo alternative splicing. This study used real-time quantitative PCR to investigate the expression of the FAMLF alternative-splicing transcript consensus sequence (FAMLF-CS) in peripheral blood mononuclear cells (PBMCs) from 119 patients with de novo acute leukemia (AL) and 104 healthy controls, as well as in CD34+ cells from 12 AL patients and 10 healthy donors. A 429-bp fragment from a novel splicing variant of FAMLF was obtained, and a 363-bp consensus sequence was targeted to quantify total FAMLF expression. Kruskal-Wallis, Nemenyi, Spearman's correlation, and Mann-Whitney U-tests were used to analyze the data. FAMLF-CS expression in PBMCs from AL patients and CD34+ cells from AL patients and controls was significantly higher than in control PBMCs (P<0.0001). Moreover, FAMLF-CS expression in PBMCs from the AML group was positively correlated with red blood cell count (rs =0.317, P=0.006), hemoglobin levels (rs =0.210, P=0.049), and percentage of peripheral blood blasts (rs =0.256, P=0.027), but inversely correlated with hemoglobin levels in the control group (rs =–0.391, P<0.0001). AML patients with high CD34+ expression showed significantly higher FAMLF-CS expression than those with low CD34+ expression (P=0.041). Our results showed that FAMLF is highly expressed in both normal and malignant immature hematopoietic cells, but that expression is lower in normal mature PBMCs.

Índice de massa corporal, circunferência da cintura e hipertensão arterial em estudantes / Índice de masa corporal, circunferencia de la cintura y hipertensión arterial en estudiantes / Body mass index, waist circumference, and arterial hypertension in students

RESUMO Objetivo: investigar qual o melhor preditor antropométrico de hipertensão arterial em alunos de escolas privadas. Método: estudo transversal, com amostra composta por 286 alunos com idade de 10 a 14 anos de duas escolas privadas de Paranavaí-Paraná. As variáveis analisadas foram: índice de massa corporal, circunferência de cintura e pressão arterial. Na análise estatística foram utilizados os testes de correlação parcial de Pearson e a regressão logística multivariada, considerando-se p<0,05. Resultados: os dois indicadores antropométricos demonstraram fracas correlações com os níveis sistólicos e diastólicos, com coeficientes (r) variando de 0,27 à 0,36 (p< 0,001). Na análise multivariada, o único indicador antropométrico associado ao risco de hipertensão arterial foi a circunferência de cintura (OR= 2,3; IC 95%: 1,1-4,5) independente da idade e gênero. Conclusão: nesta faixa etária, a circunferência de cintura parece ser melhor do que índice de massa corporal como preditor de hipertensão arterial. .

RESUMEN Objetivo: investigar cuál es el mejor predictor antropométrico de la hipertensión arterial en los alumnos de escuelas particulares. Métodos: estudio transversal con muestra compuestas por 286 alumnos con edad de 10 a 14 años de dos escuelas privadas de Paranavaí-Paraná. Las variables analizadas fueron: índice de masa corporal, circunferencia de la cintura y la presión arterial sistólica y diastólica. En el análisis de estadísticas fueron utilizadas las pruebas de correlación parcial de pearson y regresión logística multivariada considerándose p<0.05. Resultados: los dos indicadores antropométricos han mostrado débiles correlaciones con los niveles sistólicos y diastólicos, con Coeficientes (r) variando de 0,27 a 0,36 (p<0,001). En el análisis multivariado el único indicador antropométrico asociado al riesgo de hipertensión arterial fue la circunferencia de la cintura (OR=2,3; IC 95%: 1,1- 4,5) independiente de la edad y el género. Conclusión: en este grupo de edad, la circunferencia de la cintura parece ser mejor de que el índice de masa corporal como predictor de la hipertensión arterial. .

ABSTRACT Objective: to investigate what is the best anthropometric predictor of arterial hypertension among private school students. Method: this was a cross-sectional study with 286 students between the ages of 10 and 14 from two private schools in the city of Paranavaí, Paraná, Brazil. The following variables were analyzed: body mass index, waist circumference and blood pressure. Statistical analysis was conducted with Pearson’s partial correlation test and multivariate logistic regression, with p<0.05. Results: both anthropometric indicators displayed weak correlation with systolic and diastolic levels, with coeffi cients (r) ranging from 0.27 to 0.36 (p < 0.001). Multivariate analysis showed that the only anthropometric indicator associated with arterial hypertension was waist circumference (OR= 2.3; 95% CI: 1.1-4.5), regardless of age or gender. Conclusion: this age group, waist circumference appeared to be a better predictor for arterial hypertension than body mass index. .

Inmunofenotipos aberrantes en leucemias agudas en una población hospitalaria de Buenos Aires / Aberrant immunophenotypes in acute leukemia in a Buenos Aires' hospital population

La citometría de flujo multiparamétrica es el método de elección para la caracterización inmunofenotípica de las células hematopoyéticas clonales presentes en los distintos procesos leucémicos agudos. El objetivo fue analizar la expresión de antígenos de membrana y evaluar la presencia de fenotipos aberrantes en los blastos de pacientes con diagnóstico de leucemia aguda, que permiten el monitoreo de la respuesta al tratamiento. Se revisaron los inmunofenotipos de 364 muestras de pacientes adultos derivadas a nuestro laboratorio en un período de 7 años. El inmunofenotipo se realizó por citometría de flujo con un amplio panel de anticuerpos monoclonales con el que se evaluó la expresión de antígenos de linaje linfoide, mieloide y también antígenos de maduración. De las 364 muestras estudiadas, 60.2% presentaron un fenotipo compatible con leucemia mieloide aguda (LMA), 28.8% con leucemia linfoblástica B (LLA-B), 6.6% con leucemia linfoblástica T (LLA-T) y 4.4% con leucemias agudas poco frecuentes. La presencia de fenotipos aberrantes se observó en 89% de los casos, los fenotipos aberrantes identificados fueron: 1) infidelidad de linaje: LMA (54%), LLA-B (40%), LLA-T (29%); 2) ausencia de expresión antigénica: LMA (21%), LLA-B (35%), LLA-T (70%); 3) alteración de la expresión antigénica: LMA (67%), LLA-B (66%), LLA-T (84%); 4) asincronismo madurativo: LMA (26%), LLA-B (37%) y 5) fenotipo ectópico: LLA-T 96%). El análisis por citometría de flujo multiparamétrica de las leucemias agudas permitió la identificación de fenotipos aberrantes en la mayoría de nuestros pacientes, que son de utilidad para el monitoreo de la respuesta al tratamiento.

Multiparameter flow cytometry (MFC) has become the preferred method for the lineage assignment and maturational analysis of malignant cells in acute leukemias. Multiparametric immunophenotyping analysis allows the detection of aberrant antigen expression and the analysis of heterogeneity and clonality of malignant cells in leukemias. Our objectives were to analyze the membrane antigen expression and to evaluate if the aberrant phenotypes occurrence in blasts cells of patients with acute leukemia is useful in monitoring the response to the treatment. We have retrospectively analyzed the MFC data of 364 samples sent to our laboratory in a 7 years period. For this purpose we have used a large panel of monoclonal antibodies against lymphoid, myeloid and precursors antigens. From the 364 analyzed samples, 60.2% showe d a phenotype compatible with acute myeloid leukemia (AML), 28.8% with B lymphoblastic leukemia (B-LLA), 6.6% with T lymphoblastic leukemia (T-LLA) and 4.4% with rare leukemias. Aberrant phenotypes were found in 86% of the samples. The aberrant phenotypes identified were:1) lineage infidelity AML (54%), B-ALL (40%), T-ALL (29%); 2) absence of antigen expression: AML (21%), B-ALL (35%), T-ALL (70%); 3) altered antigen expression: AML (67%), B-ALL (66%),T-ALL (84%); 4) asynchronous expression: AML (26%), B-ALL (37%) and 5) ectopic phenotype: T-ALL (96%). Multiparameter flow cytometry of acute leukemias allowed identification of aberrant phenotypes in the majority of our patients, that are helpful for monitoring treatment response.

Potencial de transdiferenciação neural das células-tronco mesenquimais da medula óssea de equino / Potential of neural transdifferentiation of mesenchymal stem cells from equine bone marrow

Os primeiros estudos demonstrando o potencial de trandiferenciação neural das células-tronco mesenquimais (CTMs) provenientes da medula óssea (MO) foram conduzidos em camundogos e humanos no início da década de 2000. Após esse período, o número de pesquisas e publicações com o mesmo propósito tem aumentado, mas com raros ou escassos estudos na espécie equina. Nesse sentindo, o objetivo desse trabalho foi avaliar o potencial in vitro da transdiferenciação neural das CTMs provenientes da MO de equinos utilizando-se dois protocolos: P1 (forksolin e ácido retinóico) e P2 (2-βmecarptoetanol). Após a confirmação das linhagens mesenquimais, pela positividade para o marcador CD90 (X=97,94%), negatividade para o marcador CD34 e resposta positiva a diferenciação osteogênica, as CTMs foram submetidas a transdiferenciação neural (P1 e P2) para avaliação morfológica e expressão dos marcadores neurais GFAP e β3 tubulina por citometria de fluxo. Os resultados revelaram mudanças morfológicas em graus variados entre os protocolos testados. No protocolo 1, vinte quatro horas após a incubação com o meio de diferenciação neural, grande proporção de células (>80%) apresentaram morfologia semelhante a células neurais, caracterizadas por retração do corpo celular e grande número de projeções protoplasmáticas (filopodia). Por outro lado, de forma comparativa, já nos primeiros 30 minutos após a exposição ao antioxidante β-mercaptoetanol (P2) as CTMs apresentaram rápida mudança morfológica caracterizada principalmente por retração do corpo celular e menor número de projeções protoplasmáticas. Também ficou evidenciado com o uso deste protocolo, menor aderência das células após tempo de exposição ao meio de diferenciação, quando comparado ao P1. Com relação a análise imunofenotípica foi observado uma maior (P<0,001) expressão dos marcadores GFAP e β3 tubulina ao término do P2 quando comparado ao P1. A habilidade das CTMs em gerar tipos celulares relacionados a linhagem neural é complexa e multifatorial, dependendo não só dos agentes indutores, mas também do ambiente no qual estas células são cultivadas. Desta forma um maior número de estudos é necessário para o melhor entendimento do processo de transdiferenciação neural a partir de CTMs de equinos.

The first studies showing the potential of neural transdifferentiation of mesenchymal stem cells (MSCs) from bone marrow (BM) were conducted in camundogos and humans in the early 2000s. After this period, the number of research and publications with the same purpose increased, but with rare or scarce studies in horses. The aim of this study was to evaluate in vitro neuronal transdifferentiation potential of MSCs from equine BM using two protocols: P1 (forksolin and retinoic acid) and P2 (2-βmecarptoetanol). After confirming the mesenchymal lineages, by positivity for the marker CD90 (X=97.94%), negative for the marker CD34 and positive response for osteogenic differentiation, MSCs were subjected to neural transdifferentiation (P1 and P2) for morphological analysis and expression of neural markers GFAP and β3 tubulin by flow cytometry. The results revealed morphological changes in varying degrees between the tested protocols. In protocol 1, twenty four hours after incubation with the media of neural differentiation, a large proportion of cells (>80%) had similar morphology to neural cells, characterized by retraction of cellular body and a large number of cytoplasmic extension (filopodia). However, comparatively, within the first 30 minutes after exposure to the antioxidant β-mercaptoethanol (P2) MSCs showed rapid morphological changes characterized mainly by retraction of cellular body and less cytoplasmic extension. It was also evidenced with the use of this protocol, lower cellular adhesion after exposure to media when compared to P1. Regarding the immunophenotyping analysis it was observed a higher (P<0.001) expression of the markers GFAP and β3 tubulin at the end of P2 compared to P1. The ability of MSCs to generate cell types related to neural lineage is complex and multifactorial, depending not only of inducing agents, but also the environment in which these cells will be cultivated. Thus a greater number of studies are necessary to better understand the process of neural transdifferentiation of MSCs from equine.

Papel de las células dendríticas en la infección por HIV y HCV / The role of dendritic cells in the infection by HIV and HCV

Las células dendríticas son las principales células presentadoras de antígenos para el montaje de la respuesta inmune. Por lo tanto es importante estudiar de qué manera intervienen en el equilibrio que el sistema inmune desarrolla frente a infecciones virales persistentes como la infección por el HIV o el HCV. En esta revisión se presentan en primer término generalidades sobre las diferentes clases de células dendríticas, las características fenotípicas y funcionales que las definen y los receptores que pueden estar involucrados en la infección viral. Luego se analiza su participación en los mecanismos de defensa o facilitadores de la infección por estos virus. Es importante tener en cuenta estos conocimientos para poder diseñar adecuadas estrategias de vacunación o protección y para intentar la reconstrucción funcional del sistema inmune impidiendo la subversión de los mecanismos inmunes de defensa causada por la infección con el HIV y el HCV.

Dendritic cells are most important as antigen presenting cells during the induction of an effective immune response. Therefore, it is important to study their role during the generation of persistent or chronic viral infections, such as HIV or HCV infection. In this review we shall describe the phenotypic and functional characteristics of the different classes of dendritic cells and of their membrane receptors. Their participation in defence or facilitation mechanisms involved in the immune response against these viruses will be discussed. It is important to take this knowledge into account when trying to design therapeutic strategies for protection or reconstruction of the immune system that may be altered as a consequence of infection with HIV or HCV.

Clonagem e expressão da glicoproteína transmembrana do retrovírus HTLV-1 em células de mamíferos / Cloning and transmembrane glycoprotein expression of the retrovirus HTLV-1 in mammals' cells

O retrovírus linfotrópico de células T humanas tipo 1 é o agente etiológico da leucemia das células T do adulto e da paraparesia espástica tropical/mielopatia associada ao HTLV-1. O genoma proviral é composto por 9.032 pares de bases, contendo genes estruturais e regulatórios. A glicoproteína transmembrana gp 21 é codificada pelo gene estrutural env. O desenvolvimento de metodologias para a expressão heteróloga de proteínas, assim como a obtencão de uma linhagem celular que expresse a gp 21 recombinante constitutivamente são os principais objetivos do trabalho. O fragmento codificante da gp 21 foi amplificado por Nested-PCR e clonado no vetor pCR2.1-TOPO. Posteriormente, foi realizada a subclonagem no vetor de expressão pcDNA3.1+. A transfeccão da linhagem celular de mamíferos HEK 293 foi realizada de maneira transitória e permanente. A producão da gp 21 recombinante foi confirmada por citometria de fluxo e a linhagem celular produtora será utilizada em ensaios de imunogenicidade.

Detección de grupos de riesgo en síndromes mielodisplásicos. Un estudio multicéntrico / Detection of risk groups in myelodisplastic syndromes. A multicentric study

Los síndromes mielodisplásicos (SMD) comprenden un grupo heterogéneo de desordenes hematólogicos con riesgo de evolución a leucemia mieloide aguda (LMA). El Grupo Franco-Americano-Británico (FAB) los clasifica en cinco entidades morfológicas y el Sistema Pronóstico Internacional (IPSS) propone cuatro grupos de riesgo basándose en variables clínicas y citogenéticas. El objetivo del trabajo fue evaluar la aplicación del IPSS en población Argentina, analizar el valor pronóstico de sus variables y determinar si dicho sistema permite identificar subgrupos pronósticos de riesgo dentro de los subtipos FAB. Se evaluaron 234 pacientes con SMD de novo (Media de seguimiento: 28 meses), con el fin de determinar sobrevida (SV) y sobrevida libre de LMA (SLL). Se analizaron la clasificación FAB y el IPSS, así como sus variables (número de citopenias, porcentaje de blastos, grupos de riesgo citogenético). Los resultados mostraron diferencias significativas para SV y SLL. La aplicación del IPSS permitió la diferenciación de los cuatro grupos de riesgo y ayudó a identificar subclases pronósticas dentro de los subtipos FAB: 5 , 15 y 19 por ciento de pacientes con peor pronóstico dentro de los subtipos Anemia Refractaria (AR), AR con sideroblastos en anillo (ARSA) y AR con exceso de blastos (AREB), respectivamente. El IPSS no fue informativo para el subtipo AREB en transformación, ni tampoco en pacientes con leucemia mielomonocítica crónica.

Efecto de la cotinina en la viabilidad de fibroblastos / The effects of cotinine in fibroblasts viability

El objetivo del estudio fue evaluar "in vitro" el efecto de la cotinina en la viabilidad celular utilizando un linaje contiguo de fibroblastos. Fueron tomados grupos experimentales según las concentraciones de cotinina: 0 (control), 50mg, 100mg, 500ng, 1ug/ml y tiempo de acondicionamiento (1, 24, 48 horas). Cada uno de los 12 orificios de una placa para cultivo celular recibió 1 mL de medio de Eagle y 1mL de cotinina en las diferentes concentraciones, inmediatamente se fue acrescentando 1mL de medio de cultivo conteniendo 1x105 cels/mL. Después del acondicionamiento con la droga, en los 3 períodos ensayados, las células fueron teñidas con azul de tripan 0,4 por ciento y observadas en un microscopio invertido, por un examinador ciego, para los grupos experimentales. Los experimentos fueron repetidos 5 veces. Los resultados mostraron que las dos concentraciones mayores de cotinina presentaron los menores porcentajes de células viables, sin embargo, esta diferencia fue reducida. La viabilidad celular presentó una pequeña disminución con el aumento del tiempo de condicionamiento. Concluimos que la cotinina puede afectar la viabilidad celular sólo en las dos mayores concentraciones ensayadas

DNA degradation and its failure in programmed cell death and other developmental processes

DNA carries genes, and is important for life of cells. In some processes of mammalian development, DNA is degraded. Here, I will describe how DNA is degraded during the programmed cell death, erythropoiesis, and the lens cell differentiation, and discuss how the DNA degradation is involved to maintain mammalian homeostasis.

Cell biology, molecular embryology, Lamarckian and Darwinian selection as evolvability

The evolvability of vertebrate systems involves various mechanisms that eventually generate cooperative and nonlethal functional variation on which Darwinian selection can operate. It is a truism that to get vertebrate animals to develop a coherent machine they first had to inherit the right multicellular ontogeny. The ontogeny of a metazoan involves cell lineages that progressively deny their own capacity for increase and for totipotency in benefit of the collective interest of the individual. To achieve such cell altruism Darwinian dynamics rescinded its original unicellular mandate to reproduce. The distinction between heritability at the level of the cell lineage and at the level of the individual is crucial. However, its implications have seldom been explored in depth. While all out reproduction is the Darwinian measure of success among unicellular organisms, a high replication rate of cell lineages within the organism may be deleterious to the individual as a functional unit. If a harmoniously functioning unit is to evolve, mechanisms must have evolved whereby variants that increase their own replication rate by failing to accept their own somatic duties are controlled. For questions involving organelle origins, see Godelle and Reboud, 1995 and Hoekstra, 1990. In other words, modifiers of conflict that control cell lineages with conflicting genes and new mutant replication rates that deviate from their somatic duties had to evolve. Our thesis is that selection at the level of the (multicellular) individual must have opposed selection at the level of the cell lineage. The metazoan embryo is not immune to this conflict especially with the evolution of set-aside cells and other modes of self-policing modifiers (Blackstone and Ellison, 1998; Ransick et al., 1996. In fact, the conflict between the two selection processes permitted a Lamarckian soma-to-germline feedback loop. This new element in metazoan ontogeny became the evolvability of the vertebrate adaptive immune system and life as we know it now. We offer the hypothesis that metazoan evolution solved this ancient conflict by evolving an immunogenetic mechanism that responds with rapid Lamarckian efficiency by retaining the ancient reverse transcriptase enzyme (RNACopyright DNA copying discovered by Temin in 1959 (see Temin, 1989) and found in 1970 in RNA tumor viruses by Temin and Baltimore), which can produce cDNA from the genome of an RNA virus that infects the cells. It seems that molecular

Indução de apoptose relacionada com perda de adesão (Anoikis) em células A431 por óxido nítrico / Induction of apoptosis related with loss of adhesion (Anoikis) in A431 cells for nitric oxide

Células epiteliais, endoteliais e fibroblastos podem ser induzidas a apoptose (anoikis) quando se destacam da matriz extracelular. O processo de anoikis tem a função de proteger o organismo da colonização inapropriada destas células. O processo de apoptose pode ser induzido por vários estímulos, dentre eles, o óxido nítrico (NO). O radical livre NO pode ser sintetizado em organismos vivos pela ação das enzimas NO sintases (NOS), como também pode ser liberado por compostos doadores de NO. A geração intracelular ou extracelular de NO pode resultar em diferenciação, proliferação ou morte celular, dependendo da natureza e quantidades de NO gerado no processo, como também do tipo de celular alvo da ação do radical livre

Nuclear rDNA-based molecular clock of the evolution of triatominae (Hemiptera: Reduviidae), vectors of Chagas disease

The evolutionary history and times of divergence of triatomine bug lineages are estimated from molecular clocks inferred from nucleotide sequences of the small subunit SSU (18S) and the second internal transcribed spacer (ITS-2) of the nuclear ribosomal DNA of these reduviids. The 18S rDNA molecular clock rate in Triatominae, and Prosorrhynchan Hemiptera in general, appears to be of 1.8 per cent per 100 million years (my). The ITS-2 molecular clock rate in Triatominae is estimated to be around 0.4-1 per cent per 1 my, indicating that ITS-2 evolves 23-55 times faster than 18S rDNA. Inferred chronological data about the evolution of Triatominae fit well with current hypotheses on their evolutionary histories, but suggest reconsideration of the current taxonomy of North American species complexes.

Análise da citodiferenciaçäo de linhagens celulares derivadas de adenoma pleomórfico e de mioepitelioma humanos de glândulas salivares: estudo comparativo dos elementos citoesqueléticos e da resposta dessas células à membrana basal reconstituída (Matrigel) / Cytodifferentiation analysis of cell lines derived from human pleomorphic adenoma and human myoepithelioma: a comparative study based on the expression of cytoskeletal components and on the response of these two cell lines to a reconstituted basement

Adenoma pleomórfico e mioepitelioma säo neoplasias de glândulas salivares que exibem aspectos clínicos e histológicos semelhantes. Para avaliar o estágio de diferenciaçäo das células de maior capacidade proliferativa dessas neoplasias, utilizamos linhagens celulares derivadas de adenoma pleomórfico (AP2) e de mioepitelioma (M1). Estudamos a expressäo de proteínas citoesqueléticas, os aspectos subcelulares e a resposta das linhagens à membrana basal reconstituída (Matrigel). Células AP2 mostraram imunomarcaçäo a vimentina e citoqueratina 14, enquanto que células M1 a vimentina, pan-queratina e actina de músculo liso. Estudo subcelular da linhagem AP2 revelou características de células pouco diferenciadas. Célula M1 mostraram aspectos subcelulares de fenótipo mioepitelial bem diferenciado, exibindo feixes de microfilamentos com adensamentos focais. Após uma semana envolvidas por Matrigel, células AP2 exibiram formaçäo de estruturas ductiformes e células M1 organizaram-se em cordöes celulares. Nossos resultados indicam que células AP2 exibem fenótipo epitelial glandular neoplásico pouco diferenciado, enquanto que células M1, fenótipo mioepitelial neoplásico bem diferenciado. Admitindo-se que o adenoma pleomórfico e o mioepitelioma resultem de proliferaçäo neoplástica de células do ducto intercalado de glândulas salivares, o adenoma pleomórfico originar-se-ia de células mais indiferenciadas e permissivas, enquanto que células já comprometidas com a diferenciaçäo no sentido mioepitelial dariam origem ao mioepitelioma

Immunochemical localization of chromaffin cells during the embryogenic migration

Adrenal medulla together with the sympathetic nervous system constitute an anatomo functional unit. Both tissues derive from precursor cells which originate from the neural crest and later differentiate during migration into sympathetic neurons or chromaffin cells. Biosynthesis enzymes of catecholamines such as DBH (dopamine beta hydroxylase) and PNMT (phenylethanol amine-N-methyl transferase) as well as the neurotransmitter serotonin , can be detected by immunohistochemical techniques from 15 to 20 prenatal days. Cells migrating along the dorsal aorta could be observed at 15 prenatal days. From day 16 on, three distinct cellular groups could be distinguished according to the intensity of the immunoreactivity: chromaffin, paraganglion and sympathetic ganglion cells. From day 18, chromaffin cells immunostained as DBH' PNMT+ or DBH+ PNMT could be detected differentiating into what would be adrenergic or noradrenergic cells, respectively Progenitor cells migrating from the neural crest to the adrenal cortical blastema reach a micro-environment where glucocorticoids could possibly influence gene expression for PNMT in some of these undifferentiated cells, causing adrenaline synthesis. Serotonin(5HT) immunoreactivity is localized from 17 prenatal days in several groups of the paraganglionic cells where they could be a modulator for chromaffin differentiation.

Smooth muscle cell diversity and the extracellular matrix in a rat model of restenosis

Clear differences exist in the incidence and severity of atherosclerotic plaques that arise in different segments of the arterial tree. Aortic homograft transplant experiments in dogs showed that the greater incidence of plaque formation in the abdominal versus the thoracic aorta was due to intrinsic differences in the cell populations in these two segments rather than to hemodynamic factors. What is the basis for SMC diversity within a common vessel wall? Recent lineage analysis studies in the avian and mammalian embryo indicate that two distinct SMC lineages contribute to the formation of the major elastic outflow arteries including the aorta. A mixture of unique SMC types of diverse developmental lineages within a common vessel wall raises new questions about the potential for SMC type-specific responses to growth factors and cytokines involved in human atherosclerosis and restenosis