Lack of Prenylated Proteins, Autophagy Impairment and Apoptosis in SH-SY5Y Neuronal Cell Model of Mevalonate Kinase Deficiency

Mevalonate Kinase Deficiency (MKD), is a hereditary disease due to mutations in mevalonate kinase gene (MVK). MKD has heterogeneous clinical phenotypes: the correlation between MVK mutations and MKD clinical phenotype is still to be fully elucidated. Deficiency of prenylated proteins has been hypothesized as possible MKD pathogenic mechanism. Based on this hypothesis and considering that neurologic impairment characterizes Mevalonic Aciduria (MA), the most severe form of MKD, we studied the effects of I268T and N301T MVK mutations on protein prenylation, autophagy and programmed cell death in SH-SY5Y neuroblastoma cell lines

Fluorescent in-situ hybridization (FISH) for BCR/ABL in chronic myeloid leukemia after bone marrow transplantation

CONTEXT: Identification of Philadelphia chromosome or BCR/ABL gene rearrangement in chronic myeloid leukemia is important at diagnosis as well as after treatment. OBJECTIVE: To compare the results of karyotyping using fluorescent in-situ hybridization (FISH) upon diagnosis and 1 year after bone marrow transplantation in 12 patients. TYPE OF STUDY: Diagnostic test and residual disease detection. SETTING: Hematology and Hemotherapy Department, Federal University of São Paulo/Escola Paulista de Medicina, São Paulo, Brazil. SAMPLE: 12 patients with chronic myeloid leukemia at diagnosis and 1 year after bone marrow transplantation. DIAGNOSTIC TEST: Karyotyping was done in the usual way and the BCR/ABL gene-specific probe was used for FISH. MAIN MEASUREMENTS: Disease at diagnosis and residual. RESULTS: At diagnosis, 10 patients presented t(9;22)(q34.1;q11) as well as positive FISH. Two cases did not have metaphases but FISH was positive. After bone marrow transplantation, 8 patients presented normal karyotype, 1 had persistence of identifiable Philadelphia chromosome and 3 had no metaphases. Two cases showed complete chimera and 2 had donor and host cells simultaneously. FISH was possible in all cases after bone marrow transplantation and confirmed the persistence of identifiable Philadelphia chromosome clone in one patient, and identified another that did not present metaphases for analysis. Cases that showed mixed chimera in karyotype were negative for BCR/ABL by FISH. CONCLUSION: The applicability of FISH is clear, particularly for residual disease detection. Classical and molecular cytogenetics are complementary methods.CONTEXTO: Na leucemia mielóide crônica, a detecção do cromossomo Philadelphia ou o rearranjo gênico BCR/ABL é importante tanto ao diagnóstico como após o tratamento. OBJETIVO: Comparar os resultados do cariótipo com a hibridação in situ por fluorescência ao diagnóstico e, após um ano de transplante de medula óssea, em 12 pacientes com leucemia mielóide crônica. TIPO DE ESTUDO: Teste diagnóstico e detecção de doença residual. LOCAL: Disciplina de Hematologia e Hemoterapia da Universidade de São Paulo/Escola Paulista de Medicina. AMOSTRA: 12 pacientes com leucemia mielóide crônica ao diagnóstico e um ano após transplante de medula óssea. TESTE DIAGNÓSTICO: A análise do cariótipo (forma clássica) e a hibridação in situ por fluorescência com a sonda específica para os genes BCR/ABL. VARIÁVEIS ESTUDADAS: Doença ao diagnóstico e residual. RESULTADOS: Ao diagnóstico, 10 pacientes apresentaram t(9;22)(q34.1;q11) no cariótipo assim como pela hibridação in situ por fluorescência. Dois casos em que na citogenética não havia mitoses, apresentaram rearranjo pela hibridação in situ por fluorescência. Após o transplante de medula óssea, o cariótipo mostrou ausência do cromossomo Philadelphia em 8 casos, persistência em um e ausência de metáfases em três. Em dois casos havia quimera completa e em outros dois havia concomitância de células do doador e do receptor. A hibridação in situ por fluorescência foi possível em todos os casos após o transplante de medula óssea, confirmando a persistência do clone cromossomo Philadelphia num paciente em que o cariótipo também havia mostrado e identificando noutro em que não havia metáfases. Os casos de quimera mista foram negativos para BCR/ABL pela hibridação in situ por fluorescência. CONCLUSÃO: Ficou evidente a aplicabilidade da hibridação in situ por fluorescência, particularmente na detecção de doença residual. A citogenética clássica e a molecular são métodos complementares.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Discipline of Hematology and HemotherapyUNIFESP, EPM, Discipline of Hematology and HemotherapySciEL

del 11(q23) as a prognostic factor of iron overload in refractory anemia with ringed sideroblasts

We present the case of a patient with MDS RARS subtype with loss of part of the long arm of chromosome 11 del 11(q23). This a cytogenetic abnormality that occurs in 7% to 20% of RARS cases not related to poor prognosis. It seems that this deletion is a marker of iron overload in MDS.Apresentamos o caso de paciente com Síndrome Mielodisplásia (SMD) sublito Anemia Refratária com Sideroblastos em Anel (ARSA) com perda do braço longo do cromossomo 11 [del (q23)]. Trata-se de alteração citogenética que ocorre entre 7 e 20% dos casos de ARSA não se correlacionando a mau prognóstico, ou seja, evolução para leucemia aguda. Aparentemente, esta deleção é um marcador de sobrecarga de ferro na SMD.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM)UNIFESP, EPMSciEL

Acute Myeloid Leukemia t(8;21) after treatment for hyperthyroidism using radioactive iodine: Secondary Leukemia?

Acute leukemia following treatment with Iodine131 is a rare event. The possible carcinogenic effect of Iodine131 is still not clear and a large series of cases did not show an increased incidence of cancer. A case of AML t(8;21), three years after Iodine131 treatment for hyperthyroidism, is reported. Secondary AML with t(8;21) is described following exposure to drugs that target topoisomerase II and radiotherapy. The controversial potential of Iodine131 as a leukemogenic agent and the fact that t(8;21) is also found in de-novo AML, emphasize the problem in establishing a relationship between these events although this potential can not be ruled out.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM)UNIFESP, EPMSciEL

Detection of trisomy 12 by fluorescent in situ hybridization (FISH) in chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) presents a varying incidence of karyotypic abnormalities whose detection is complicated by difficulties in obtaining mitosis for analysis in this type of mature lymphocyte disorder. Since the introduction of molecular cytogenetics (FISH = fluorescent in situ hybridization), applying centromeric probes for chromosome 12 has made it possible to detect a higher percentage of trisomy 12 cases. The objective of the present study was to detect trisomy 12 by FISH (alpha satellite probe) in 13 patients with CLL whose karyotypes by G-banding were either normal or inadequate. Using this method trisomy 12 was detected in three patients in a percentage of positive cells varying from 55.5% to 79%, showing that FISH is a sensitive and highly specific method for trisomy detection and should be routinely performed when the karyotype is normal.A leucemia linfocítica crônica (CLL) apresenta incidência variável de anomalias de cariótipo devido às dificuldades em se obter mitose para análise. Desde a introdução da citogenética molecular (FISH = hibridação in situ por fluorescência) usando sonda centromérica para o cromossomo 12 foi possível detectar uma maior porcentagem de casos com trissomia 12. O objetivo deste trabalho foi de detectar trissomia 12 por FISH (sonda alfa satélite) em 13 pacientes com CLL cujos cariótipos por banda G haviam sido normais ou sem resultado. Três pacientes apresentaram trissomia 12 por este método com uma porcentagem de células trissômicas variando de 55,5 a 79%, demonstrando que a FISH é um método sensível e altamente específico para detecção de trissomia 12.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Disciplina de Hematologia e HemoterapiaUNIFESP, EPM, Disciplina de Hematologia e HemoterapiaSciEL

The use of wireless technology for thoracic physical examination: a pilot case based on a literature review

Auscultation is a standard method of physical examination used by physicians and is widely accepted by doctors and patients for its simplicity, repeatability and non-invasiveness. Artificial intelligence is the 'new integrated frontier' of the thoracic examination, yet there are still concordance discrepancies in obstructive pulmonary diseases; on the contrary, for fibrotic diseases, the degree of concordance increases significantly, as shown by previous clinical studies conducted mainly in children. However, there are data in the literature that appear to be very discordant on certain types of lung noises, such as wet crackles and dry noises; therefore, the application of these devices in daily use in outpatient and hospital settings needs to be further expanded. The integrated data allowed us to make the right diagnosis, also avoiding costs for the national health system and possible invasive procedures such as bronchoscopy, which today remains the “gold standard” for the histological diagnosis of sarcoidosis with lung localisation. Integrated technology could improve the diagnostic capacity in restrictive lung diseases, as shown in this clinical case. Several randomised controlled trials are still needed to increase the significance of this initial integrated research work performe

The Lantern Vol. 69, No. 1, Fall 2001

• Frets • Burn • The Amish-Man • City Children • Coasting West • Futile • Oxymoron • Fleeting Reflection • Pink Geraniums • Moving • Running: Arcola • Expectations • One Time Deal • We Slept • Faraway Field • My Own Giselle • My Father\u27s Will • Meet Me in Montana • Pride is a Lawn Mower • Gloss • 2% Low Fat • Bits of Tuesday • This is not a Pipe • What Ifs • Reconnection • A Bell Called Emily • The Elevatorhttps://digitalcommons.ursinus.edu/lantern/1159/thumbnail.jp

The Rise and Fall of "Respectable" Spanish Liberalism, 1808-1923: An Explanatory Framework

The article focuses on the reasons behind both the consolidation of what I have termed “respectable” liberalism between the 1830s and the 1840s and its subsequent decline and fall between 1900 and 1923. In understanding both processes I study the links established between “respectable” liberals and propertied elites, the monarchy, and the Church. In the first phase these links served to consolidate the liberal polity. However, they also meant that many tenets of liberal ideology were compromised. Free elections were undermined by the operation of caciquismo, monarchs established a powerful position, and despite the Church hierarchy working with liberalism, the doctrine espoused by much of the Church was still shaped by the Counter-Reformation. Hence, “respectable” liberalism failed to achieve a popular social base. And the liberal order was increasingly denigrated as part of the corrupt “oligarchy” that ruled Spain. Worse still, between 1916 and 1923 the Church, monarch, and the propertied elite increasingly abandoned the liberal Monarchist Restoration. Hence when General Primo de Rivera launched his coup the rug was pulled from under the liberals’ feet and there was no one to cushion the fall

Myelodysplastic syndromes: analysis of the most frequently cytogentic-molecular abnormalities and the influency in survival

Nas sindromes mielodisplasicas o estudo do cariotipo e fundamental nao somente ao diagnostico, como tambem na determinacao de tratamento e prognostico. A citogenetica com banda G ou citogenetica classica (CC), apesar de ser o metodo mais utilizado para esta avaliacao apresenta algumas desvantagens como a impossibilidade de avaliar celulas que nao estejam em mitose. Atraves da citogenetica molecular ou FISH (fluorescence in situ hybridization) esta avaliacao pode ser feita tanto durante a mitose quanto durante a interfase, possibilitando com isto a analise de um numero maior de celulas. Alguns estudos tem demonstrado maior sensibilidade de metodo FISH em relacao a CC na deteccao anormalidades cromossomicas de algumas neoplasias hematologicas. Os objetivos deste estudo sao: I) Avaliar pelo FISH a frequencia das seguintes anormalidades cromossomicas nas SMD: +8, -7, -5/5q-, -Y (em homens) e del 11 q23 (ARSA); 2) Comparar o FISH com a CC na deteccao destas alteracoes; 3) Avaliar a importancia destas anormalidades na sobrevida dos pacientes com SNM; 4) Avaliar a aplicabilidade do indice internacional de prognostico (IPSS) na populacao em estudo. Resultados: Atraves da CC detectaram-se alteracoes em 36,3 por cento dos casos. A associacao com o FISH aumentou esta porcentagem para 47,1 por cento. A frequencia das anormalidades pesquisadas pelo FISH foi a seguinte: del 5q/-5: 20 por cento; -7:15 por cento, +8:5 por cento- del 11 q23: 25 por cento(das ARSAS) e -Y: 6,6 por cento dos homens. A sobrevida dos pacientes com cariotipo normal foi de 37,1 meses e daqueles com a cariotipo anormal de 25,8 meses. Esta diferenca foi estatisticamente significante (p=O,OO8). O IIPSS foi aplicado em 31 pacientes, sendo 10 (32,2 por cento) de baixo risco, 7 (22,5 por cento) de risco intermediario I (INT-I), 4 (l2,9O/o) de risco intermediario 11 (INT-H) e 10 (32,2 por cento) de alto risco. A analise de sobrevida destes grupos mostrou o seguinte: Baixo risco: 41,5 meses, risco intermediario (INT-1 e INT-2): 43,3 meses e alto risco: 8,8 meses. Discussao: O FISH mostrou-se um metodo eficaz na deteccao das principais alteracoes cromossomicas das SMD, entretanto a associacao do FISH com a CC, mostrou-se mais eficaz que o uso dos 2metodos separadamente. A frequencia das anormalidades pesquisadas foi compativel com a maioria dos estudos na literatura. Os pacientes com cariotipo anormal tiveram sobrevida mais curta que aqueles com cariotipo normal, devendo portanto ...(au)BV UNIFESP: Teses e dissertaçõe