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We present a patient who developed, after an early-onset, a stable course of spastic paraplegia and ataxia for 4 decades and eventually succumbed to two episodes of postinfectious lactic acidosis. Diagnostic workup including muscle biopsy and postmortem analysis, oxymetric analysis, spectrophotometric enzyme analysis, and MitoExome sequencing revealed a necrotizing leukoencephalomyelopathy due to the so far unreported biallelic variant of the NDUFV1 gene (p.(Pro122Leu)). This case extends our understanding of NDUFV1 variants with a 14-fold longer lifetime than so far reported cases, and will foster sensitivity toward respiratory chain disease also in adult patients with sudden deteriorating neurological deficits.
Assuntos
Ataxia Cerebelar , Paraplegia Espástica Hereditária , Adulto , Ataxia , Ataxia Cerebelar/genética , Complexo I de Transporte de Elétrons/genética , Humanos , Paraplegia/genética , Paraplegia Espástica Hereditária/genéticaRESUMO
Casein kinase II contributes to the growth and survival of malignant gliomas and attracts increasing attention as a therapeutic target in these tumors. Several reports have suggested that this strategy might be most relevant for specific subgroups of patients, namely Verhaak's classical and TP53 wild-type tumors. Using kinase assays and microarray genetic profiling in a series of 27 proprietary fresh frozen surgical glioma samples, we showed that constitutive CK2 kinase activation is not restricted to tumors that present increased copy numbers or mRNA expression of its catalytic or regulatory subunits, and can result from a functional activation by various cytokines from the glioma microenvironment. Using corresponding primary tumor and human astrocyte cell cultures as well as glioma cell lines, we confirmed that CK2 inhibition is selectively toxic to malignant glial tumors, without any restriction to tumor class or to TP53 status. We finally showed that while the contribution of CK2 to the constitutive NF-κB hyperactivation in malignant gliomas is at best moderate, a delayed activation of NF-κB may associate with the therapeutic resistance of glioma cells to CK2 inhibition.
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Neoplasias Encefálicas/enzimologia , Perfilação da Expressão Gênica/métodos , Glioblastoma/enzimologia , Análise Serial de Tecidos/métodos , Apigenina/farmacologia , Neoplasias Encefálicas/genética , Caseína Quinase II/antagonistas & inibidores , Caseína Quinase II/genética , Caseína Quinase II/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Ativação Enzimática , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Humanos , Naftiridinas/farmacologia , Fenazinas , Microambiente Tumoral , Proteína Supressora de Tumor p53/genéticaRESUMO
BACKGROUND: Glioblastomas remain ominous tumors that almost invariably escape treatment. Connexins are a family of transmembrane, gap junction-forming proteins, some members of which were reported to act as tumor suppressors and to modulate cellular metabolism in response to cytotoxic stress. METHODS: We analyzed the copy number and expression of the connexin (Cx)30 gene gap junction beta-6 (GJB6), as well as of its protein immunoreactivity in several public and proprietary repositories of glioblastomas, and their influence on patient survival. We evaluated the effect of the expression of this gap junction protein on the growth, DNA repair and energy metabolism, and treatment resistance of these tumors. RESULTS: The GJB6 gene was deleted in 25.8% of 751 analyzed tumors and mutated in 15.8% of 158 tumors. Cx30 immunoreactivity was absent in 28.9% of 145 tumors. Restoration of Cx30 expression in human glioblastoma cells reduced their growth in vitro and as xenografts in the striatum of immunodeficient mice. Cx30 immunoreactivity was, however, found to adversely affect survival in 2 independent retrospective cohorts of glioblastoma patients. Cx30 was found in clonogenic assays to protect glioblastoma cells against radiation-induced mortality and to decrease radiation-induced DNA damage. This radioprotection correlated with a heat shock protein 90-dependent mitochondrial translocation of Cx30 following radiation and an improved ATP production following this genotoxic stress. CONCLUSION: These results underline the complex relationship between potential tumor suppressors and treatment resistance in glioblastomas and single out GJB6/Cx30 as a potential biomarker and target for therapeutic intervention in these tumors.
Assuntos
Neoplasias Encefálicas/genética , Conexinas/genética , Glioma/genética , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/radioterapia , Linhagem Celular Tumoral , Proliferação de Células/genética , Conexina 30 , Conexinas/metabolismo , Deleção de Genes , Glioma/mortalidade , Glioma/radioterapia , Proteínas de Choque Térmico HSP90/metabolismo , Xenoenxertos/metabolismo , Humanos , Proteínas Inibidoras de Apoptose/metabolismo , Estimativa de Kaplan-Meier , Camundongos , Mitocôndrias/metabolismo , RNA Mensageiro/metabolismo , SurvivinaRESUMO
A 57-year-old male with no family history was diagnosed with semantic dementia. He also showed some unusual cognitive features such as episodic memory and executive dysfunctions, spatial disorientation, and dyscalculia. Rapidly progressive cognitive and physical decline occurred. About 1.5 years later, he developed clinical features of a corticobasal syndrome. He died at the age of 60. Brain autopsy revealed numerous 4R-tau-positive lesions in the frontal, parietal and temporal lobes, basal ganglia, and brainstem. Neuronal loss was severe in the temporal cortex. Such association of semantic dementia with tauopathy and corticobasal syndrome is highly unusual. These findings are discussed in the light of current knowledge about frontotemporal lobar degeneration.
Assuntos
Demência Frontotemporal/diagnóstico , Encéfalo/patologia , Demência Frontotemporal/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Tauopatias/complicações , Tauopatias/patologiaRESUMO
BACKGROUND: SV2A, SV2B and SV2C are synaptic vesicle proteins that are structurally related to members of the major facilitator superfamily (MFS). The function and transported substrate of the SV2 proteins is not clearly defined although they are linked to neurotransmitters release in a presynaptic calcium concentration-dependent manner. SV2A and SV2B exhibit broad expression in the central nervous system while SV2C appears to be more restricted in defined areas such as striatum. SV2A knockout mice start to display generalized seizures at a late developmental stage, around post-natal day 7 (P7), and die around P15. More recently, SV2A was demonstrated to be the molecular target of levetiracetam, an approved anti-epileptic drug (AED). The purpose of this work was to precisely analyze and quantify the SV2A, SV2B and SV2C expression during brain development to understand the contribution of these proteins in brain development and their impact on epileptic seizures. RESULTS: First, we systematically analyzed by immunohistofluorescence, the SV2A, SV2B and SV2C expression during mouse brain development, from embryonic day 12 (E12) to P30. This semi-quantitative approach suggests a modulation of SV2A and SV2B expression in hippocampus around P7. This is the reason why we used various quantitative approaches (laser microdissection of whole hippocampus followed by qRT-PCR and western blot analysis) indicating that SV2A and SV2B expression increased between P5 and P7 and remained stable between P7 and P10. Moreover, the increase of SV2A expression in the hippocampus at P7 was mainly observed in the CA1 region while SV2B expression in this region remains stable. CONCLUSIONS: The observed alterations of SV2A expression in hippocampus are consistent with the appearance of seizures in SV2A-/- animals at early postnatal age and the hypothesis that SV2A absence favors epileptic seizures around P7.
Assuntos
Encéfalo/embriologia , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Glicoproteínas de Membrana/biossíntese , Proteínas do Tecido Nervoso/biossíntese , Convulsões/metabolismo , Animais , Western Blotting , Imunofluorescência , Glicoproteínas de Membrana/análise , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Microdissecção , Proteínas do Tecido Nervoso/análise , Isoformas de Proteínas/análise , Isoformas de Proteínas/biossínteseRESUMO
BACKGROUND: Neurodegenerative diseases are characterized by key features such as loss of neurons, astrocytosis, and microglial activation/proliferation. These changes cause differences in the density of cell types between control and disease subjects, confounding results from gene expression studies. Chromosome X (ChrX) is known to be specifically important in the brain. We hypothesized the existence of a chromosomal signature of gene expression associated with the X-chromosome for neurological conditions not normally associated with that chromosome. The hypothesis was investigated using publicly available microarray datasets from studies on Parkinson's disease, Alzheimer's disease, and Huntington's disease. Data were analyzed using Chromowave, an analytical tool for detecting spatially extended expression changes along chromosomes. To examine associations with neuronal density and astrocytosis, the expression of cell specific reporter genes was extracted. The association between these genes and the expression patterns extracted by Chromowave was then analyzed. Further analyses of the X:Autosome ratios for laser dissected neurons, microglia cultures and whole tissue were performed to detect cell specific differences. RESULTS: We observed an extended pattern of low expression of ChrX consistent in all the neurodegenerative disease brain datasets. There was a strong correlation between mean ChrX expression and the pattern extracted from the autosomal genes representing neurons, but not with mean autosomal expression. No chromosomal patterns associated with the neuron specific genes were found on other chromosomes. The chromosomal expression pattern was not present in datasets from blood cells. The X:Autosome expression ratio was also higher in neuronal cells than in tissues with a mix of cell types. CONCLUSIONS: The results suggest that neurological disorders show as a reduction in mean expression of many genes along ChrX. The most likely explanation for this finding relates to the documented general up-regulation of ChrX in brain tissue which, this work suggests, occurs primarily in neurons. If validated, this cell specific ChrX expression warrants further research as understanding the biological reasons and mechanisms for this expression, may help to elucidate a connection with the development of neurodegenerative disorders.
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BACKGROUND: Multiple choroid plexus papillomas (CPPs) are rare. Usually, they correspond to villous hypertrophy or metastasis occurring during cerebrospinal dissemination. Multiple CPPs have rarely been reported as synchronous tumors. CASE REPORT: Three synchronous CPPs were resected in a 59-year-old female 6 years after their first imaging description. Pathology showed mucus-producing CPP in all 3, 1 of the 3 presenting some signs of atypia. No p53 or hSNF5/INI1 mutation, or signs of polyoma viruses infection were found. CONCLUSION: Although no clear cause for the multifocality was found, the simultaneous presence of the three tumors and their benign histology suggest that they were synchronous and not metastatic. The issue of differentiating synchronous CPPs from metastatic CPP is discussed.
Assuntos
Neoplasias Primárias Múltiplas/patologia , Papiloma do Plexo Corióideo/patologia , Feminino , Humanos , Hidrocefalia de Pressão Normal/complicações , Hidrocefalia de Pressão Normal/cirurgia , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/complicações , Papiloma do Plexo Corióideo/complicações , Derivação VentriculoperitonealAssuntos
Transplante de Córnea , Células Epiteliais/patologia , Epitélio Corneano/patologia , Ceratomileuse Assistida por Excimer Laser In Situ , Complicações Pós-Operatórias , Células-Tronco/patologia , Biomarcadores/metabolismo , Células Epiteliais/metabolismo , Epitélio Corneano/metabolismo , Humanos , Imuno-Histoquímica , Fenótipo , Células-Tronco/metabolismoRESUMO
PURPOSE: To report the first case of choroidal schwannoma in a patient affected by PTEN hamartoma tumor syndrome (PHTS) and investigate the molecular involvement of the phosphatase and tensin homolog (PTEN) and neurofibromin 2 (NF2) genes in this rare intraocular tumor. DESIGN: Observational case report. PARTICIPANT: A 10-year-old girl diagnosed with PHTS. METHODS: The enucleated specimen underwent histologic, immunohistochemical, and transmission electronic microscopy. The expression of PTEN and NF2 and their protein products were evaluated by reverse transcription-polymerase chain reaction and immunohistochemistry. Somatic mutations of PTEN and NF2, as well as allelic loss, were investigated by direct sequencing of DNA extracted from the tumor. PTEN epigenetic silencing was investigated by pyrosequencing. MAIN OUTCOME MEASURES: Histopathologic and molecular characterization of a choroidal pigmented schwannoma. RESULTS: Histopathologic, immunohistochemical, and electron microscopic analysis demonstrated features consistent with a pigmented cellular schwannoma of the choroid. We found no loss of heterozygosity at the genomic level for the PTEN germline mutation and no promoter hypermethylation or other somatic intragenic mutations. However, we observed an approximate 40% reduction of PTEN expression at both the mRNA and the protein level, indicating that the tumor was nonetheless functionally deficient for PTEN. Although DNA sequencing of NF2 failed to identify any pathologic variants, its expression was abolished within the tumor. CONCLUSIONS: We report the first description of a pigmented choroidal schwannoma in the context of a PHTS. This rare tumor showed a unique combination of reduction of PTEN and absence of NF2 expression.
Assuntos
Neoplasias da Coroide/genética , Síndrome do Hamartoma Múltiplo/genética , Neurilemoma/genética , Neurofibromina 2/genética , PTEN Fosfo-Hidrolase/genética , Criança , Neoplasias da Coroide/diagnóstico por imagem , Neoplasias da Coroide/patologia , Metilação de DNA , Análise Mutacional de DNA , DNA de Neoplasias/genética , Enucleação Ocular , Feminino , Síndrome do Hamartoma Múltiplo/diagnóstico por imagem , Síndrome do Hamartoma Múltiplo/patologia , Humanos , Imuno-Histoquímica , Neurilemoma/diagnóstico por imagem , Neurilemoma/patologia , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ultrassonografia , Acuidade VisualAssuntos
Cistos Aracnóideos/complicações , Cistos Aracnóideos/diagnóstico , Cisto Epidérmico/complicações , Cisto Epidérmico/diagnóstico , Cefaleia , Adulto , Cistos Aracnóideos/patologia , Cistos Aracnóideos/cirurgia , Serviços Médicos de Emergência , Cisto Epidérmico/patologia , Cisto Epidérmico/cirurgia , Cefaleia/diagnóstico , Cefaleia/etiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios XAssuntos
Anticorpos Monoclonais/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Linfoma/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados , Encéfalo/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , NatalizumabRESUMO
In patients with glioblastoma multiforme, recurrence is the rule despite continuous advances in surgery, radiotherapy and chemotherapy. Within these malignant gliomas, glioblastoma stem cells or initiating cells have been recently described, and they were shown to be specifically involved in experimental tumorigenesis. In this study, we show that some human glioblastoma cells injected into the striatum of immunodeficient nude mice exhibit a tropism for the subventricular zones. There and similarily to neurogenic stem cells, these subventricular glioblastoma cells were then able to migrate toward the olfactory bulbs. Finally, the glioblastoma cells isolated from the adult mouse subventricular zones and olfactory bulbs display high tumorigenicity when secondary injected in a new mouse brain. Together, these data suggest that neurogenic zones could be a reservoir for particular cancer-initiating cells.
Assuntos
Neoplasias Encefálicas/patologia , Movimento Celular , Ventrículos Cerebrais/patologia , Glioblastoma/patologia , Células-Tronco Neoplásicas/patologia , Bulbo Olfatório , Animais , Corpo Estriado , Feminino , Humanos , Camundongos , Camundongos Nus , Transplante de Neoplasias , Transplante HeterólogoRESUMO
BACKGROUND: Sulfasalazine, a NF-kappaB and x(c)-cystine/glutamate antiport inhibitor, has demonstrated a strong antitumoral potential in preclinical models of malignant gliomas. As it presents an excellent safety profile, we initiated a phase 1/2 clinical study of this anti-inflammatory drug for the treatment of recurrent WHO grade 3 and 4 astrocytic gliomas in adults. METHODS: 10 patients with advanced recurrent anaplastic astrocytoma (n = 2) or glioblastoma (n = 8) aged 32-62 years were recruited prior to the planned interim analysis of the study. Subjects were randomly assigned to daily doses of 1.5, 3, 4.5, or 6 grams of oral sulfasalazine, and treated until clinical or radiological evidence of disease progression or the development of serious or unbearable side effects. Primary endpoints were the evaluation of toxicities according to the CTCAE v.3.0, and the observation of radiological tumor responses based on MacDonald criteria. RESULTS: No clinical response was observed. One tumor remained stable for 2 months with sulfasalazine treatment, at the lowest daily dose of the drug. The median progression-free survival was 32 days. Side effects were common, as all patients developed grade 1-3 adverse events (mean: 7.2/patient), four patients developed grade 4 toxicity. Two patients died while on treatment or shortly after its discontinuation. CONCLUSION: Although the proper influence of sulfasalazine treatment on patient outcome was difficult to ascertain in these debilitated patients with a large tumor burden (median KPS = 50), ISRCTN45828668 was terminated after its interim analysis. This study urges to exert cautiousness in future trials of Sulfasalazine for the treatment of malignant gliomas. TRIAL REGISTRATION: Current Controlled Trials ISRCTN45828668.
Assuntos
Término Precoce de Ensaios Clínicos , Glioma/tratamento farmacológico , Sulfassalazina/administração & dosagem , Adulto , Progressão da Doença , Feminino , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sulfassalazina/efeitos adversos , Falha de TratamentoRESUMO
Glioblastomas (GBMs) are the most frequent and malignant brain tumors in adults. Glucocorticoids (GCs) are routinely used in the treatment of GBMs for their capacity to reduce the tumor-associated edema. Few in vitro studies have suggested that GCs inhibit the migration and invasion of GBM cells through the induction of MAPK phosphatase 1 (MKP-1). Macrophage migration inhibitory factor (MIF), an endogenous GC antagonist is up-regulated in GBMs. Recently, MIF has been involved in tumor growth and migration/invasion and specific MIF inhibitors have been developed on their capacity to block its enzymatic tautomerase activity site. In this study, we characterized several glioma cell lines for their MIF production. U373 MG cells were selected for their very low endogenous levels of MIF. We showed that dexamethasone inhibits the migration and invasion of U373 MG cells, through a glucocorticoid receptor (GR)- dependent inhibition of the ERK1/2 MAPK pathway. Oppositely, we found that exogenous MIF increases U373 MG migration and invasion through the stimulation of the ERK1/2 MAP kinase pathway and that this activation is CD74 independent. Finally, we used the Hs 683 glioma cells that are resistant to GCs and produce high levels of endogenous MIF, and showed that the specific MIF inhibitor ISO-1 could restore dexamethasone sensitivity in these cells. Collectively, our results indicate an intricate pathway between MIF expression and GC resistance. They suggest that MIF inhibitors could increase the response of GBMs to corticotherapy.
Assuntos
Neoplasias Encefálicas/metabolismo , Dexametasona/farmacologia , Regulação da Expressão Gênica , Glioma/metabolismo , Fatores Inibidores da Migração de Macrófagos/antagonistas & inibidores , Fatores Inibidores da Migração de Macrófagos/metabolismo , Antineoplásicos Hormonais/farmacologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Relação Dose-Resposta a Droga , Humanos , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Modelos Biológicos , Invasividade Neoplásica , Fatores de TempoRESUMO
Somatostatin analogs (SSA) with their potent antisecretory and antiproliferative effects are the main medical treatment option for patients with neuroendocrine tumors, such as gastroenteropancreatic and acromegaly-associated growth hormone secreting pituitary tumors. Although a good portion of acromegalic patients gets normalized after SSA treatment, strict hormonal control is not achieved in a sizeable proportion of these patients. The reasons for this incomplete response to SSA treatment are unclear. We have found that the tumor suppressor ZAC1 (LOT1/PLAGL1) is essential for the antiproliferative effect of SSA in pituitary tumor cells. The aim of the present retrospective cohort study was to determine whether ZAC1 immunoreactivity in archival somatotrophinoma tissue derived from 45 patients with acromegaly routinely pretreated with SSA before surgery, was associated with response to SSA (normalization of GH, IGF-I and presence of tumor shrinkage). All tumors displayed ZAC1 immunoreactivity [weak (+; n = 15), moderate (++; n = 16) and strong (+++; n = 14)]. A significant positive correlation was found between strong ZAC1 immunoreactivity and IGF-I normalization and presence of tumor shrinkage after SSA treatment, which was not affected by age at diagnosis, gender or duration of SSA treatment. These in vivo data combined with the antiproliferative properties of ZAC1/Zac1 provide evidence of a mechanistic role for this transcription factor on SSA induced tumor shrinkage and hormone normalization.
Assuntos
Acromegalia/tratamento farmacológico , Proteínas de Ciclo Celular/análise , Octreotida/uso terapêutico , Peptídeos Cíclicos/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Somatostatina/análogos & derivados , Fatores de Transcrição/análise , Proteínas Supressoras de Tumor/análise , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Neoplasias Hipofisárias/química , Estudos Retrospectivos , Somatostatina/uso terapêuticoRESUMO
Eyelid tumors are the most common neoplasm in daily ophthalmology practice and encompass a wide variety of benign and malignant tumors. In this retrospective study, we report the clinical and histological features of 5504 eyelid skin tumors diagnosed at the Laboratory of Ophthalmopathology of the Hôpital Ophtalmique Jules Gonin, Lausanne, Switzerland, between January 1989 and December 2007. Benign tumors largely predominated over malignant ones, representing 84% of cases in this series, and the 5 most frequent subtypes were squamous cell papilloma (26%), seborrheic keratosis (21%), melanocytic nevus (20%), hidrocystoma (8%), and xanthoma/xanthelasma (6%). Basal cell carcinoma was the most frequent malignant tumor (86%), followed by squamous cell carcinoma (7%) and sebaceous carcinoma (3%). For several tumor subtypes, there was a poor correlation between clinical and histological diagnosis, stressing the numerous pitfalls in the diagnosis of eyelid tumors. We further discuss our results with reference to previously published series.
Assuntos
Doenças Palpebrais/patologia , Neoplasias Palpebrais/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/patologia , Criança , Pré-Escolar , Feminino , Hidrocistoma/patologia , Humanos , Lactente , Ceratose Seborreica/patologia , Masculino , Pessoa de Meia-Idade , Nevo Pigmentado/patologia , Papiloma/patologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Neoplasias das Glândulas Sebáceas/patologia , Neoplasias Cutâneas/patologia , Neoplasias das Glândulas Sudoríparas/patologia , Xantomatose/patologia , Adulto JovemRESUMO
OBJECTIVE: To use contrast-enhanced coded phase-inversion harmonic B-mode sonography to assess the acoustic enhancement of the synovial area of the knee; and to compare the data with the histological vessel density. METHODS: Eleven patients eligible for a knee arthroscopy were studied. Acoustic quantification was carried out by a digital image analysis program that detects the time-dependent increase [intensity (time) = k x time + C] of gray-level intensity in all the pixels of a specific region of interest (ROI) following intravenous injection of the microbubble contrast agent sulfur hexafluoride. Echo-guided synovial biopsies were carried out in the same ROI. Synovial vessel areas were quantified after Factor VIII immunostaining of synovial biopsies using an automated digital image analysis. RESULTS: Significant (p < 0.05) correlations were observed between histological vessel density and percentage of the synovial area with a k value > 0.01 (r = 0.93) and k(max) values (r = 0.79), as well as between the 2 latter parameters (r = 0.72). The histological vessel density and the 2 acoustic parameters were also significantly correlated with the logarithm of erythrocyte sedimentation rate (r = 0.77, r = 0.87, r = 0.67, respectively) and with log C-reactive protein serum concentration (r = 0.69, r = 0.83, r = 0.62, respectively). CONCLUSION: Contrast-enhanced coded phase-inversion harmonic B-mode sonography coupled with an appropriate data analysis method is a new tool to identify and quantify vessel density in knee synovitis.
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Processamento de Imagem Assistida por Computador/métodos , Articulação do Joelho/irrigação sanguínea , Articulação do Joelho/diagnóstico por imagem , Sinovite/diagnóstico por imagem , Sinovite/patologia , Ultrassonografia Doppler/métodos , Adulto , Idoso , Biópsia , Sedimentação Sanguínea , Vasos Sanguíneos/diagnóstico por imagem , Vasos Sanguíneos/patologia , Proteína C-Reativa/metabolismo , Meios de Contraste , Feminino , Humanos , Articulação do Joelho/patologia , Masculino , Microbolhas , Pessoa de Meia-Idade , Membrana Sinovial/irrigação sanguínea , Membrana Sinovial/diagnóstico por imagem , Membrana Sinovial/patologia , Sinovite/sangueRESUMO
Gliomas are the most common CNS tumours in children and present either as circumscribed tumours or diffusely infiltrative neoplasms. Diffuse gliomas develop both in the cerebral hemispheres and the brainstem and have a poor prognosis. Guidelines for the therapy of these tumours are still debated. In this study, we reviewed the clinical features of 27 consecutive patients with diffuse gliomas admitted to the Department of Paediatrics of CHR Citadelle, University of Liège, between 1985 and 2005. We review their clinical presentation, diagnosis, treatment and outcome with reference to the published literature.
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Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Glioma/patologia , Glioma/terapia , Adolescente , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/fisiopatologia , Criança , Pré-Escolar , Feminino , Glioma/fisiopatologia , Humanos , Lactente , Masculino , Procedimentos Neurocirúrgicos , Estudos RetrospectivosRESUMO
Recent studies suggested that Huntington's disease is due to aberrant interactions between mutant huntingtin protein, transcription factors and transcriptional co-activators resulting in widespread transcriptional dysregulation. Mutant huntingtin also interacts with histone acetyltransferases, consequently interfering with the acetylation and deacetylation states of histones. Because histone modifications and chromatin structure coordinate the expression of gene clusters, we have applied a novel mathematical approach, Chromowave, to analyse microarray datasets of brain tissue and whole blood to understand how genomic regions are altered by the effects of mutated huntingtin on chromatin structure. Results show that, in samples of caudate and whole blood from Huntington's disease patients, transcription is indeed deregulated in large genomic regions in coordinated fashion, that transcription in these regions is associated with disease progression and that altered chromosomal clusters in the two tissues are remarkably similar. These findings support the notion of a common genome-wide mechanism of disruption of RNA transcription in the brain and periphery of Huntington's disease patients.
Assuntos
Aberrações Cromossômicas , Doença de Huntington/genética , Núcleo Caudado/metabolismo , Interpretação Estatística de Dados , Progressão da Doença , Feminino , Regulação da Expressão Gênica , Humanos , Proteína Huntingtina , Doença de Huntington/sangue , Doença de Huntington/metabolismo , Masculino , Mutação , Proteínas do Tecido Nervoso/genética , Proteínas Nucleares/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Transcrição GênicaRESUMO
BACKGROUND: Impotence and decreased libido are the cardinal features of prolactinomas in males. We describe the unusual clinical, pathological and biochemical features in a male patient with a giant prolactinoma and normal gonadal function. CASE REPORT: A 57 year-old man presented with visual symptoms related to a 30x25x60mm tumor of the sella and skull base. Biopsy revealed a pituitary adenoma and subsequent hormone profiles demonstrated grossly elevated serum prolactin (131,412ng/ml), LH at the upper limit of normal and normal testosterone. The patient had no symptoms of decreased libido or impotence related to this giant prolactinoma. Immunohistochemistry revealed a tumor that was positive for prolactin, alpha-subunit and LH. Cabergoline greatly reduced prolactin levels but these remained above normal. LH, testosterone and alpha-subunit levels were decreased in parallel. Loss of libido and impotence became apparent when testosterone fell below normal, a situation that resolved with further cabergoline treatment and prolactin inhibition and testosterone therapy. CONCLUSIONS: Sexual dysfunction is a hallmark of prolactinomas in males. Tumors that co-secrete prolactin and LH are extremely rare and this is the first such case reported in an adult male. In this case, normal testosterone was maintained by intact LH levels even in the face of the highest prolactin level reported to date.