Preferential induction of MLL (Mixed Lineage Leukemia) rearrangements in human lymphocyte cultures treated with etoposide

Topoisomerase II inhibitors are effective chemotherapeutic agents in the treatment of cancer, in spite of being associated with the development of secondary leukemia. Our purpose was to determine the effects of etoposide on different genomic regions, aiming at discovering whether there are preferential sites which can be targeted by this drug in peripheral lymphocytes from healthy individuals. The in vitro treatment with low doses of etoposide (0.25, 0.5, and 1 µg/mL, in 1 hour-pulse or continuous-48 h treatment) induced a significant increase in chromosomal aberrations, detected by conventional staining and FISH with specific probes for chromosomes 8 and 11, compared with untreated controls (p < 0.05). Additionally, the frequencies of alterations at 11q23, detected by MLL specific probes, were significantly higher (p < 0.005) in treated cells than in controls. In contrast, an analysis of rearrangements involving the IGH gene did not disclose differences between treatments. The present results demonstrated the potential of etoposide to interact with preferential chromosome sites in human lymphocytes, even at concentrations below the mean plasma levels measured in cancer patients. This greater susceptibility to etoposide-induced cleavage may explain the more frequent involvement of MLL in treatment-related leukemia.FAPESPCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)CNP

Chondrolysis of the hip in an adolescent: clinical and radiological outcomes

Idiopathic chondrolysis of the hip is a rare condition of unknown etiology characterized by progressive destruction of the hyaline cartilage that covers the femoral head and acetabulum. Idiopathic chondrolysis of the hip has an insidious beginning and affects more often female adolescents. Patients report severe hip pain, mobility limitation, and even claudication. This study aimed at reporting one case of that rare disease: an 11-year-old female adolescent with chondrolysis, followed up for three years. Inflammatory activity tests were normal. Imaging tests (radiography, ultrasonography and magnetic resonance) were essential for the diagnosis. The treatment was based on pain control and preservation of the joint mobility, and included low-impact physical activity, non-steroidal anti-inflammatory drugs, and disease-modifying antirheumatic drugs, with good response after 12 months of treatment. Surgery was not necessary.A condrólise idiopática de quadril é uma condição rara, caracterizada por destruição progressiva da cartilagem articular da cabeça do fêmur e do acetábulo, sem etiologia conhecida. A CIQ tem início insidioso e acomete com maior frequência meninas na adolescência. Os pacientes apresentam dor intensa em quadril, restrição de movimentação e até claudicação. O objetivo do trabalho foi demonstrar um caso dessa doença rara: uma adolescente de 11 anos de idade, com condrólise, em acompanhamento por três anos. As provas de atividade inflamatória eram normais. Os exames de imagem (radiografia, ultrassonografia e ressonância magnética) foram essenciais para o diagnóstico. O tratamento baseou-se no controle da dor e preservação da mobilidade articular, incluindo atividades físicas de baixo impacto, anti-inflamatórios não hormonais e droga modificadora de doença, com boa resposta após um ano de tratamento. Intervenção cirúrgica não foi necessária.Universidade Federal de São Paulo (UNIFESP) Departamento de Pediatria Setor de Reumatologia PediátricaSanta Casa de Misericórdia de São Paulo Departamento de PediatriaUniversidade Federal de São Paulo (UNIFESP) Departamento de Diagnóstico por ImagemUNIFESP, Depto. de Pediatria Setor de Reumatologia PediátricaUNIFESP, Depto. de Diagnóstico por ImagemSciEL

Ictal spitting in left temporal lobe epilepsy: Report of three cases

Purpose: Ictal spitting is rarely reported in patients with epilepsy. More often it is observed in patients with temporal lobe epilepsy (TLE) and is presumed to be a lateralizing sign to language nondominant hemisphere. We report three patients with left TLE who had ictal spitting registered during prolonged video-EEG monitoring.Methods: Medical charts of all patients with medically refractory partial epilepsy submitted to prolonged video-EEG monitoring in the Epilepsy Unit at UNIFESP during a 3-year period were reviewed, in search of reports of ictal spitting. the clinical, neurophysiological and neuroimaging data of the identified patients were reviewed.Results: Among 136 patients evaluated with prolonged video-EEG monitoring, three (2.2%) presented spitting automatisms during complex partial seizures. All of them were right-handed, and had clear signs of left hippocampal sclerosis on MRI. in two patients, in all seizures in which ictal spitting was observed, EEG seizure onset was seen in the left temporal lobe. in the third patient, ictal onset with scalp electrodes was observed in the right temporal lobe, but semi-invasive monitoring with foramen ovate electrodes revealed ictal onset in the left temporal lobe, confirming false lateralization in surface records. the three patients became seizure-free following left anterior temporal lobectomy.Conclusions: Ictal spitting is a rare finding in patients with epilepsy, and may be considered a localizing sign of seizure onset in the temporal lobe. It may be observed in seizures originating from the left temporal lobe, and thus should not be considered a lateralizing sign of nondominant TLE. (C) 2006 British Epilepsy Association. Published by Elsevier B.V. All rights reserved.Univ São Paulo, Ribeirao Preto Sch Med, Div Neurol, Dept Neurol Psychiat & Clin Psychol, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Radiol, Div Neuroradiol, São Paulo, BrazilUniversidade Federal de São Paulo, Div Neurol, Dept Neurol & Neurosurg, UNIPETE, BR-04024002 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Radiol, Div Neuroradiol, São Paulo, BrazilUniversidade Federal de São Paulo, Div Neurol, Dept Neurol & Neurosurg, UNIPETE, BR-04024002 São Paulo, BrazilWeb of Scienc

Cytogenetic Instability in Childhood Acute Lymphoblastic Leukemia Survivors

Contemporary anticancer therapies have largely improved the outcome for children with cancer, especially for Acute Lymphoblastic Leukemia (ALL). Actually, between 78% and 85% of patients achieve complete remission and are alive after 5 years of therapy completion. However, as cure rates increase, new concerns about the late effects of genotoxic treatment emerge, being the risk of developing secondary neoplasias, the most serious life-threatening rising problem. In the present paper, we describe and review the cytogenetic findings in peripheral lymphocytes from ALL survivors, and discuss aspects associated to the occurrence of increased chromosome rearrangements in this growing cohort

Promiscuous Gene Expression in the Thymus: The Root of Central Tolerance

The thymus is a complex organ with an epithelium formed by two main cell types, the cortical thymic epithelial (cTECs) and medullary thymic epithelial cells (mTECs), referred to as stroma. Immature thymocytes arising from the bone marrow, macrophages and dendritic cells also populate the thymus. Thymocytes evolve to mature T cells featuring cell differentiation antigens (CDs), which characterize the phenotypically distinct stages, defined as double-negative (DN), double positive (DP) and single positive (SP), based on expression of the coreceptors CD4 and CD8. The thymus is therefore implicated in T cell differentiation and during development into T cells thymocytes are in close association with the stroma. Recent evidence showed that mTECs express a diverse set of genes coding for parenchymal organ specific proteins. This phenomenon has been termed promiscuous gene expression (PGE) and has led to the reconsideration of the role of the thymus in central T cell tolerance to self-antigens, which prevents autoimmunity. The evidence of PGE is causing a reanalysis in the scope of central tolerance understanding. We summarize the evidence of PGE in the thymus, focusing particularly the use of cDNA microarray technology for the broad characterization of gene expression and demarcation of PGE emergence during thymus ontogeny

Communicative processes of individuals with injuries of the right cerebral hemisphere

Objective: This study aimed to profile the language skills of patients with damage to the right cerebral hemisphere attended at the Ibirapuera Unit (Central) of the Association for the Welfare of Handicapped Children - AACD (Associação de Assistência à Criança Deficiente - AACD/Unidade Ibirapuera - Central), and to discover the perceptions of caregivers and patients regarding the presence or absence of language disorders after a stroke. Method: The descriptive study was conducted from July to September of 2009 with 11 adults through the application of the Montreal Communication Evaluation Battery (known in Brazil as Bateria MAC) tests, the Questionnaire on Awareness of Difficulties, and the Communicative Disorders Screening on individuals with neurological conditions, direct relatives, and/or caregivers. Results: It was found that 90.9% of patients with injuries of the right cerebral hemisphere had a deficit in at least one of the tests comprising the Bateria MAC assessment of language. Conclusion: Findings showing the patient’s absence of awareness of their linguistic and cognitive deficits are also very important, not only about their daily life activities, but about their agnosia.Objetivo: O presente estudo teve como objetivo traçar o perfil de linguagem de pacientes com lesão de hemisfério direito atendidos na Associação de Assistência a Criança Deficiente (AACD/Unidade Ibirapuera - Central), bem como verificar a percepção dos cuidadores e dos pacientes em relação à presença ou não de alterações de linguagem pós-acidente vascular cerebral. Método: O estudo descritivo foi desenvolvido de julho a setembro de 2009 com 11 indivíduos adultos por meio da aplicação da Bateria Montreal de Avaliação da Comunicação/Bateria MAC, prova Questionário sobre a Consciência das Dificuldades e o questionário Triagem de Distúrbios Comunicativos em Indivíduos com quadro neurológico, direcionado aos familiares e/ou cuidadores. Resultados: Verificou-se que 90,9% dos pacientes com Lesão de Hemisfério Direito apresentaram déficit em pelo menos uma das provas que compunham a Bateria MAC de avaliação da linguagem. Conclusão: Mostra-se também de extrema importância o achado relacionado à ausência de percepção dos pacientes em relação as suas próprias alterações linguístico-cognitivas, não pela inexistência de impactos em sua vida diária, mas devido à agnosia

Hemispheric surgery for refractory epilepsy in children and adolescents: Outcome regarding seizures, motor skills and adaptive function

Purpose: the aim of the study was to report the seizure outcome, motor skills and adaptive motor functions in a series of children and adolescents who underwent hemispheric surgery, analysing the risk-benefits of surgery.Methods: the clinical course, seizure and motor function outcomes of 15 patients who underwent hemispheric surgery were reviewed.Results: the mean age at surgery was 9.5, with 1-9 years follow-up. the underlying pathologies were Rasmussen encephalitis, vascular disorders, and hemimegalencephaly. All the patients presented with severe epilepsy and different degrees of hemiparesis, although motor functionality was preserved in 80% of the patients. At last follow-up, 67% were seizure free, and 20% rarely experienced seizures. Antiepileptic drugs were reduced in 60%, and complete withdrawal from such drugs was successful in 20% of the patients. the motor outcome following the surgery varied between the patients.Despite the motor deficit after surgery, the post-operative motor function showed unchanged for gross motor function in most (60%), while 27% improved. Similar results were obtained for the ability to handle objects in daily life activities. Sixty percent of the children were capable of handling objects, with somewhat reduced coordination and/or motor speed.Conclusion: Pre-surgical motor function continues to play a role in the pre-surgical evaluation process in order to provide a baseline for outcome. Hemispheric surgery, once regarded as a radical intervention and last treatment resource, may become routinely indicated for refractory hemispheric epilepsy in children and adolescents, with oftentime favourable motor outcomes. (C) 2013 British Epilepsy Association. Published by Elsevier B.V. All rights reserved.Universidade Federal de São Paulo, Hosp São Paulo, Dept Neurol & Neurocirurgia, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Diagnost Imagem, São Paulo, BrazilInst Neurol & Neurocirugia Cuba, Dept Neuropediat, Havana 10400, CubaUniv São Paulo, Fac Med Ribeirao Preto, Dept Neurociencias & Ciencias Comportamento, BR-14049 Ribeirao Preto, SP, BrazilUniversidade Federal de São Paulo, Hosp São Paulo, Dept Neurol & Neurocirurgia, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Diagnost Imagem, São Paulo, BrazilWeb of Scienc

Application and performance of disease activity indices proposed for patients with systemic sclerosis in an international cohort of patients with juvenile systemic sclerosis

Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: the inception cohort project is supported by an unrestricted grant from the Joachim Herz Stiftung, Hamburg, Germany. Publisher Copyright: © The Author(s) 2023.Objectives: Juvenile systemic sclerosis is a rare childhood disease. Three disease activity indices have been published for adult patients with systemic sclerosis: the European Scleroderma Study Group Index, a modified version of the European Scleroderma Study Group Index and the revised European Scleroderma Trials and Research index. The objective of this study was to determine the feasibility and performance of the three disease activity indices in a prospectively followed cohort of patients with juvenile systemic sclerosis. Methods: The analysis cohort was selected from the prospective international inception cohort enrolling juvenile systemic sclerosis patients. The correlation of the disease activity indices with the physicians’ and the patients’ global assessment of disease activity was determined. The disease activity indices were compared between patients with active and inactive disease. Sensitivity to change between 6- and 12-month follow-up was investigated by mixed models. Results: Eighty percent of the 70 patients had a diffuse cutaneous subtype. The revised European Scleroderma Trials and Research index was highly correlated with the physician-reported global disease activity/parents-reported global disease activity (r = 0.74/0.64), followed by the European Scleroderma Study Group activity index (r = 0.61/0.55) and the modified version of the European Scleroderma Study Group activity index (r = 0.51/0.43). The disease activity indices significantly differed between active and inactive patients. The disease activity indices showed sensitivity to change between 6- and 12-month follow-up among patients who improved or worsened according to the physician-reported global disease activity and the parents-reported global disease activity. Conclusion: Overall, no disease activity score is superior to the other, and all three scores have limitations in the application in juvenile systemic sclerosis patients. Furthermore, research on the concept of disease activity and suitable scores to measure disease activity in patients with juvenile systemic sclerosis is necessary in future.Peer reviewe

Support for UNRWA's survival

The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) provides life-saving humanitarian aid for 5·4 million Palestine refugees now entering their eighth decade of statelessness and conflict. About a third of Palestine refugees still live in 58 recognised camps. UNRWA operates 702 schools and 144 health centres, some of which are affected by the ongoing humanitarian disasters in Syria and the Gaza Strip. It has dramatically reduced the prevalence of infectious diseases, mortality, and illiteracy. Its social services include rebuilding infrastructure and homes that have been destroyed by conflict and providing cash assistance and micro-finance loans for Palestinians whose rights are curtailed and who are denied the right of return to their homeland

MLL leukemia-associated rearrangements in peripheral blood lymphocytes from healthy individuals

Chromosomal translocations are characteristic of hematopoietic neoplasias and can lead to unregulated oncogene expression or the fusion of genes to yield novel functions. In recent years, different lymphoma/leukemia-associated rearrangements have been detected in healthy individuals. In this study, we used inverse PCR to screen peripheral lymphocytes from 100 healthy individuals for the presence of MLL (Mixed Lineage Leukemia) translocations. Forty-nine percent of the probands showed MLL rearrangements. Sequence analysis showed that these rearrangements were specific for MLL translocations that corresponded to t(4;11)(q21;q23) (66%) and t(9;11) (20%). However, RT-PCR failed to detect any expression of t(4;11)(q21;q23) in our population. We suggest that 11q23 rearrangements in peripheral lymphocytes from normal individuals may result from exposure to endogenous or exogenous DNA-damaging agents. In practical terms, the high susceptibility of the MLL gene to chemically-induced damage suggests that monitoring the aberrations associated with this gene in peripheral lymphocytes may be a sensitive assay for assessing genomic instability in individuals exposed to genotoxic stress