RESUMO
Fused in sarcoma (FUS) is a DNA/RNA-binding protein associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. The exact molecular mechanisms by which FUS results in neurotoxicity have not yet been fully elucidated. Here, we found that parkin is a genetic suppressor of defective phenotypes induced by exogenous human wild type FUS in Drosophila. Although parkin overexpression did not modulate the FUS protein expression level, the locomotive defects in FUS-expressing larvae and adult flies were rescued by parkin expression. We found that FUS expression in muscle tissues resulted in a reduction of the levels and assembly of mitochondrial complex I and III subunits, as well as decreased ATP. Remarkably, expression of parkin suppressed these mitochondrial dysfunctions. Our results indicate parkin as a neuroprotective regulator of FUS-induced proteinopathy by recovering the protein levels of mitochondrial complexes I and III. Our findings on parkin-mediated neuroprotection may expand our understanding of FUS-induced ALS pathogenesis.
Assuntos
Esclerose Lateral Amiotrófica/genética , Drosophila/metabolismo , Proteína FUS de Ligação a RNA/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Trifosfato de Adenosina/metabolismo , Esclerose Lateral Amiotrófica/patologia , Animais , Animais Geneticamente Modificados , Modelos Animais de Doenças , Drosophila/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Larva , Masculino , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Músculos/metabolismo , Músculos/patologia , Proteína FUS de Ligação a RNA/genética , Ubiquitina-Proteína Ligases/genéticaRESUMO
Heavy alcohol consumption leads to neuropathological damage and alcohol use disorder, which affects the health of people and results in a cost burden. However, the genes modulating sensitivity to ethanol remain largely unknown. Here, we identified a novel gene, Drosophila glutathione transferase omega 1 (GstO1), which plays a critical role in regulating sensitivity to ethanol sedation. GstO1 mutant flies showed highly increased ethanol sensitivity. Furthermore, the expression level of GstO1 regulates the behavioural response to ethanol, because decreasing and increasing GstO1 affects sedation sensitivity in a contrasting manner. In addition, the RNA interference-mediated knockdown of GstO1 expression reveals that GstO1 mediates sensitivity to ethanol sedation in neurones, including dopaminergic and serotonergic neurones. Altogether, our findings provide the first evidence for the involvement of glutathione transferase in the response to alcohol in Drosophila and provide a novel mechanistic insight into the toxicity and sensitivity of ethanol exposure.
Assuntos
Depressores do Sistema Nervoso Central/toxicidade , Proteínas de Drosophila/metabolismo , Drosophila/enzimologia , Etanol/toxicidade , Glutationa Transferase/metabolismo , Neurônios/efeitos dos fármacos , Animais , Drosophila/efeitos dos fármacos , Drosophila/genética , Proteínas de Drosophila/genética , Glutationa Transferase/genética , MasculinoRESUMO
BACKGROUND AND PURPOSE: MR imaging is the primary tool for evaluation and monitoring of spinal tumors. We retrospectively analyzed the MR imaging findings before and after SRS for metastatic spinal tumors. MATERIALS AND METHODS: We reviewed MR imaging findings on 79 metastatic spinal tumor lesions in 44 patients (29 male and 15 female)who had undergone radiosurgery between November 2003 and April 2008. Posttreatment MR imaging was evaluated retrospectively for 3 aspects: 1) changes in tumor volume; 2) changes in T2 signal intensity;and 3) changes in contrast enhancement patterns. RESULTS: With regard to tumor volume on MR images, 32 lesions(40.5%) decreased in volume (group 1), 39 (49.4%) showed no change (group 2), and 8 (10.1%) increased in volume (group 3). T2 signal intensities were unchanged in 4 lesions (type 1), homogeneously increased in 3 (type 2), and changed to a homogeneously dark signal in 4 (type 4). The T2 signal intensity was increased and inter mixed with dark signal intensity (type 3) in 68 lesions. A decrease in contrast enhancement with or without non-enhancing foci was seen in 73 lesions. A persistent homogeneous enhancement pattern was seen in all 4 of the type 1 lesions, in 1 of the 3 type 2 lesions, and in 1 of the 68 type 3 lesions. CONCLUSIONS: Main MR imaging features of locally controlled metastatic spinal tumors included no increase in tumor volume, increased T2 signal intensity with intermixed T2 dark signal intensity,and decreased contrast enhancement. Follow-up MR imaging also provided several patterns of tumor recurrence [corrected].
Assuntos
Imageamento por Ressonância Magnética , Radiocirurgia , Neoplasias da Medula Espinal/diagnóstico , Neoplasias da Medula Espinal/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Medula Espinal/secundárioRESUMO
SUMMARY: We report the serial MR findings and histologic features of intracerebral xanthoma in a patient with hyperlipidemia. MR imaging revealed nodule formations with variable degrees of edema and enhancement in the perivascular spaces. In some lesions, high-signal-intensity foci were observed on unenhanced T1-weighted images, which suggest lipid contents of the lesion.
Assuntos
Encefalopatias/diagnóstico , Ventrículos Cerebrais , Imageamento por Ressonância Magnética , Xantomatose/diagnóstico , Gânglios da Base/patologia , Doenças dos Gânglios da Base/diagnóstico , Biópsia , Encefalopatias/patologia , Ventrículos Cerebrais/patologia , Diagnóstico Diferencial , Feminino , Células Espumosas/patologia , Seguimentos , Lobo Frontal/patologia , Humanos , Pessoa de Meia-Idade , Xantomatose/patologiaRESUMO
BACKGROUND: We evaluated the clinical efficacy and technical feasibility of the percutaneously inserted self-expandable nitinol stent (Zilver stent) for palliation of malignant biliary obstruction. METHODS: Seventeen patients with malignant tumors involving the intra- or extrahepatic bile duct who presented with obstructive jaundice underwent percutaneous insertion of a self-expandable nitinol stent. We retrospectively reviewed the hospital records of patients and evaluated the technical feasibility on stent placement, complications, patient survival, and duration of stent patency. RESULTS: Percutaneous biliary stenting with 27 Zilver stents was performed in 17 patients with malignant biliary obstruction. Technical success was 95%. Malposition of the stent was encountered in one patient. Minor technical problems were encountered in two patients: the introducer tip was broken during stent insertion, so endoscopic removal was done. Mean follow-up period for the 17 patients was 182 days (range 29-485 days): nine patients died of progressive disease at a mean follow-up of 151 days (range 61-371days) after stent insertion and eight patients remained alive at the final follow-up of 216 days (range 29-485 days). The median survival period for all patients was 277 days. The stent occlusion rate was 26% and the mean patency period was 280 days. In five patients, seven stents were obstructed by tumor ingrowth and overgrowth. Stent patency rates were 100%, 100%, 75%, 61%, and 41% at 1, 2, 3, 6, and 12 months, respectively. A late complication, erosive bleeding of the hepatic artery by the stent, developed in one patient. CONCLUSION: Percutaneous biliary stenting using the nitinol stent is technically feasible and safe and clinically efficacious treatment for malignant biliary obstruction, even with a minor technical problem during stent insertion.
Assuntos
Neoplasias dos Ductos Biliares/complicações , Colestase/terapia , Stents , Idoso , Idoso de 80 Anos ou mais , Ligas , Neoplasias dos Ductos Biliares/mortalidade , Colestase/etiologia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Stents/efeitos adversos , Taxa de SobrevidaRESUMO
Ten iridoviruses were isolated from cultured fish from various regions in Korea; 7 from rock bream, 1 from red sea bream, 1 from sea bass, and 1 from rockfish. The full open-reading frame (ORF) encoding the major capsid protein (MCP) (1362 bp) from ten iridoviruses were sequenced and the nucleotide sequences were phylogenetically analyzed. Phylogenetic analysis revealed that the ten Korean isolates were classified into one cluster. However, their sequences were not identical and, based on the nucleotide sequence variation, they could be further divided into two subgroups. While nine Korean isolates were similar to the Japanese isolate red sea bream iridovirus (RSIV), one isolate was distinct from other iridovirus isolates. These results suggest that a diversity of iridoviruses exist in Korea and that a new variant strain has emerged.
Assuntos
Proteínas do Capsídeo/genética , Infecções por Vírus de DNA/veterinária , Doenças dos Peixes/virologia , Iridoviridae/genética , Sequência de Aminoácidos , Animais , Infecções por Vírus de DNA/virologia , Peixes , Genes Virais , Variação Genética , Iridoviridae/isolamento & purificação , Coreia (Geográfico) , Dados de Sequência Molecular , Fases de Leitura Aberta , Filogenia , Alinhamento de SequênciaRESUMO
Recombinant proteins of truncated viral protein-2 (VP2) (aa 79-359) and VP3 of infectious pancreatic necrosis virus (IPNV) and marine birnavirus (MABV) were expressed in E. coli and their immunogenicities in fish were investigated. The recombinant proteins from IPNV were used to immunize rainbow trout and those from MABV to immunize flounder. The sera from the immunized fishes were assayed for antibody by ELISA and a neutralization test. Both the recombinant VP2 and VP3 produced antibodies in fish but the VP3 antibody titers were higher than that of the VP2 of IPNV and MABV. These results indicate that the recombinant VP3 is more immunogenic than the recombinant VP2.
Assuntos
Birnaviridae/imunologia , Vírus da Necrose Pancreática Infecciosa/imunologia , Oncorhynchus mykiss/imunologia , Proteínas Estruturais Virais/imunologia , Animais , Anticorpos Antivirais/sangue , Birnaviridae/genética , Clonagem Molecular , Ensaio de Imunoadsorção Enzimática , Escherichia coli/genética , Escherichia coli/metabolismo , Vírus da Necrose Pancreática Infecciosa/genética , Testes de Neutralização , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação , Proteínas Estruturais Virais/genéticaRESUMO
PURPOSE: The purpose of this work was to evaluate the usefulness of CT scans for distinguishing torsed from uncomplicated benign cystic teratoma (BCT). METHOD: Retrospective analysis was performed in 14 torsed BCTs (14 patients) and in 23 uncomplicated BCTs (20 patients) for comparison. The features on CT scans were compared to the pathologic findings. RESULTS: CT findings indicating torsed BCT were the presence of eccentric wall thickening of >1 cm, peritumoral infiltration, and presence of enlarged solid tubal mass adjacent to the uterus (p < 0.05). CONCLUSION: The present study suggests that CT is useful in differentiating torsed from uncomplicated BCT. Although CT findings are not specific for some patients, detection of certain CT findings could increase the diagnostic accuracy.
Assuntos
Neoplasias Ovarianas/diagnóstico por imagem , Teratoma/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Distribuição de Qui-Quadrado , Criança , Diagnóstico Diferencial , Doenças das Tubas Uterinas/diagnóstico por imagem , Feminino , Hemorragia/diagnóstico por imagem , Humanos , Histerossalpingografia , Infarto/diagnóstico por imagem , Isquemia/diagnóstico por imagem , Pessoa de Meia-Idade , Neoplasias Ovarianas/irrigação sanguínea , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Teratoma/irrigação sanguínea , Teratoma/patologia , Anormalidade Torcional/diagnóstico por imagem , Anormalidade Torcional/patologiaRESUMO
We have cloned and sequenced a cDNA encoding GTP-binding protein from a fish cell, CHSE-214. The clone was 1493 bp long and contained an open reading frame encoding 364 amino acids. It has the five sequence motifs G1-G5 that are conserved in all GTP-binding proteins. Its amino acid sequences are strikingly different from those of the well-characterized G-proteins. However, sequences closely related to this protein are found in various kinds of species including human, Arabidopsis, Drosophila and archaebacteria, suggesting a novel subfamily within the superfamily of the GTP-binding proteins. Northern analysis indicates that this gene is constitutively expressed at a low level in normal cells but is induced by fish rhabdovirus infection at about 24 h post infection and disappears thereafter. Based on these observations, we propose that this protein represents an evolutionarily conserved novel subfamily of GTP-binding proteins which may play an important role in fish rhabdovirus infection.
Assuntos
Doenças dos Peixes/virologia , Proteínas de Ligação ao GTP/genética , Infecções por Rhabdoviridae/veterinária , Salmão/genética , Sequência de Aminoácidos , Animais , Clonagem Molecular , Evolução Molecular , Proteínas de Ligação ao GTP/classificação , Dados de Sequência Molecular , Filogenia , Homologia de Sequência de AminoácidosRESUMO
A 90 kDa cellular protein in a fish cell, CHSE-214, showed increased expression by the infection of infectious hematopoietic necrosis virus (IHNV), heat shock, 2-mercaptoethanol, copper sulfate, and cadmium sulfate, and was detected in various kinds of cells such as human, rat, and mouse cells. The molecular mass of the 90 kDa protein was different from those of the hsp90 and grp94. In addition, all the anti-stress protein MAbs did not react with the 90 kDa protein. Finally, the subcellular distribution of the 90 kDa protein, determined by Western blots of subcellular fractions, was found to be mainly nuclear, both in normal and IHNV-infected CHSE-214 cells. The present results indicate that the 90 kDa protein is a kind of stress protein. However, based on its molecular mass, antigenic characteristics, and subcellular distribution, it is likely that this protein is a novel stress protein that has not been previously described in animal systems, especially in fish systems.
Assuntos
Proteínas de Choque Térmico HSP90/biossíntese , Proteínas Nucleares/biossíntese , Infecções por Rhabdoviridae/metabolismo , Animais , Anticorpos Monoclonais/imunologia , Compostos de Cádmio/farmacologia , Linhagem Celular , Sulfato de Cobre/farmacologia , Reações Cruzadas , Eletroforese em Gel de Poliacrilamida , Fungicidas Industriais/farmacologia , Proteínas de Choque Térmico HSP90/química , Proteínas de Choque Térmico HSP90/imunologia , Temperatura Alta , Humanos , Mercaptoetanol/farmacologia , Camundongos , Peso Molecular , Proteínas Nucleares/química , Proteínas Nucleares/imunologia , Ratos , Salmão , Sulfatos/farmacologiaRESUMO
Intussusception associated with Yersinia pseudotuberculosis infection was developed in three boys; two of them had a history of drinking untreated water. All intussusceptions were localized at the ileocolic region, and all patients completely recovered with Gastrografin enema and supportive treatment without complication and operation.
Assuntos
Doenças do Íleo/microbiologia , Intussuscepção/microbiologia , Infecções por Yersinia pseudotuberculosis/complicações , Criança , Pré-Escolar , Humanos , Doenças do Íleo/diagnóstico , Intussuscepção/diagnóstico , Masculino , Yersinia pseudotuberculosis/isolamento & purificação , Infecções por Yersinia pseudotuberculosis/diagnósticoRESUMO
OBJECTIVE: The purpose of this study was to analyze the CT findings in 10 patients with abdominal actinomycosis to determine the appearance of lesions and the pattern of spread of the disease. MATERIALS AND METHODS: We retrospectively reviewed the CT findings in 10 patients with pathologically proved actinomycosis. Involved areas were the pelvis (n = 4), greater omentum (n = 3), liver (n = 2), and kidney (n = 1). Contrast-enhanced (oral and IV) CT scans were available in all patients. Unenhanced CT scans were also available in six patients. RESULTS: CT scans showed mostly solid masses with focal areas of diminished attenuation in seven patients and mostly cystic masses with thickened walls in three. CT findings confirmed the infiltrative nature of the disease, showing its tendency to invade across tissue planes and boundaries. Dense inhomogeneous contrast enhancement in the walls or solid components of masses was seen in eight patients. Minimal lymphadenopathy was seen in only two patients. CONCLUSION: Although nonspecific, actinomycosis should be included in the differential diagnosis when CT scans show an infiltrative mass with unusual aggressiveness and dense inhomogeneous contrast enhancement, especially in patients with fever, leukocytosis, or long-term use of intrauterine contraceptive devices.
Assuntos
Actinomicose/diagnóstico por imagem , Radiografia Abdominal , Tomografia Computadorizada por Raios X , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pelve/diagnóstico por imagem , Estudos RetrospectivosRESUMO
Monoclonal antibodies were prepared from hybridoma clones isolated by the fusion of myeloma cells and spleen cells derived from mice immunized with either purified rabbit liver microsomal cytochrome P-450LM2 or cytochrome P-450LM4. Seven hybridoma clones produced three kinds of monoclonal antibodies to P-450LM2. The first class bound, precipitated, and inhibited the enzyme activity of P-450LM2 for both benzo[a]pyrene hydroxylation and 7-ethoxycoumarin deethylation. The other two classes either bound and precipitated or only bound the enzyme. These monoclonal antibodies to P-450LM2 showed a precipitin reaction and inhibition of enzyme activity that was specific for cytochrome P-450LM2. Thus, they did not react with or inhibit the enzyme activity of the other isozyme cytochrome P-450LM4, Fraction 1 or Fraction 7. All of the monoclonal antibodies formed against P-450LM2 were mouse immunoglobulin (Ig) subclass IgG1. The most effective monoclonal antibody strongly inhibited the formation of oxygenated metabolites of benzo[a]pyrene at various positions as well as the deethylation of 7-ethoxycoumarin. Four hybridomas were isolated which produced monoclonal antibodies to P-450LM4. One of the four was of the IgM class and three were of the IgG1 type. The four monoclonal antibodies bound to P-450LM4 but did not precipitate the enzyme, and did not bind to P-450LM2. The monoclonal antibody P-450LM4 complexes interacted with protein A, and the enzyme activity for benzo[a]pyrene hydroxylation could be removed by centrifugation. The high specificity and monoclonality of these antibodies suggest their potential usefulness for studying the genetics, regulation, and roles of the different isozymes of P-450LM in drug and carcinogen metabolism.