RESUMO
Japan provides many lessons for the Environmental Neurology's issues. Drama and disasters have paved the recent history of Japan. The Japanese people have been intoxicated by chemical compounds (methylmercury, sulfur dioxide, cadmium, PCBs and other dioxin-related compounds) and were the victims of several dramatic disasters (atomic bombing, nuclear disaster, sarin gas attack). They are still exposed to air pollution. Prion diseases including dura-graft-associated CJD are still an issue. In addition, continuously spreading chronic wasting disease is a worldwide challenge .
Assuntos
Encefalopatias , Encéfalo/fisiologia , Meio Ambiente , Fenômenos Fisiológicos do Sistema Nervoso , Encéfalo/efeitos dos fármacos , Encefalopatias/induzido quimicamente , Encefalopatias/epidemiologia , Poluentes Ambientais/toxicidade , Acidente Nuclear de Fukushima , História do Século XX , História do Século XXI , Humanos , Japão/epidemiologia , Sistema Nervoso/efeitos dos fármacos , Fenômenos Fisiológicos do Sistema Nervoso/efeitos dos fármacos , Sarina/toxicidadeRESUMO
BACKGROUND AND PURPOSE: Akinetic mutism is thought to be an appropriate therapeutic end-point in patients with sporadic Creutzfeldt-Jakob disease (sCJD). However, prognostic factors for akinetic mutism are unclear and clinical signs or symptoms that precede this condition have not been defined. The goal of this study was to identify prognostic factors for akinetic mutism and to clarify the order of clinical sign and symptom development prior to its onset. METHODS: The cumulative incidence of akinetic mutism and other clinical signs and symptoms was estimated based on Japanese CJD surveillance data (455 cases) collected from 2003 to 2008. A proportional hazards model was used to identify prognostic factors for the time to onset of akinetic mutism and other clinical signs and symptoms. RESULTS: Periodic synchronous discharges on electroencephalography were present in the majority of cases (93.5%). The presence of psychiatric symptoms or cerebellar disturbance at sCJD diagnosis was associated with the development of akinetic mutism [hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.14-1.99, and HR 2.15, 95% CI1.61-2.87, respectively]. The clinical course from cerebellar disturbance to myoclonus or akinetic mutism was classified into three types: (i) direct path, (ii) path via pyramidal or extrapyramidal dysfunction and (iii) path via psychiatric symptoms or visual disturbance. CONCLUSIONS: The presence of psychiatric symptoms or cerebellar disturbance increased the risk of akinetic mutism of sCJD cases with probable MM/MV subtypes. Also, there appear to be sequential associations in the development of certain clinical signs and symptoms of this disease.
Assuntos
Síndrome de Creutzfeldt-Jakob/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Afasia Acinética/epidemiologia , Afasia Acinética/etiologia , Doenças Cerebelares/complicações , Doenças Cerebelares/epidemiologia , Síndrome de Creutzfeldt-Jakob/epidemiologia , Síndrome de Creutzfeldt-Jakob/fisiopatologia , Progressão da Doença , Eletroencefalografia , Feminino , Humanos , Incidência , Imageamento por Ressonância Magnética , Masculino , Transtornos Mentais/complicações , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Mioclonia/epidemiologia , Mioclonia/etiologia , Valor Preditivo dos Testes , PrognósticoRESUMO
OBJECTIVES: Clinical and pathological significance of gadolinium (Gd)-enhancing pattern on magnetic resonance imaging (MRI), including ring enhancement (RE), is well documented in multiple sclerosis but not in neuromyelitis optica (NMO), especially in the spinal cord. The purpose of this study is to examine the prevalence of spinal cord RE in NMO and to determine the association between clinical characteristics and spinal cord RE. MATERIALS AND METHODS: We retrospectively examined Gd-enhanced spinal cord MRI scans, during the acute phase, in patients with anti-aquaporin 4-positive NMO, including NMO spectrum disorder. We then analysed their clinical features and MRI imaging characteristics of spinal cord lesions. RESULTS: Of the 30 patients with NMO, we enrolled 12 patients with 16 Gd-enhanced spinal cord MRI scans in this study. Five scans revealed RE (31.2%). Male ratio, as well as myelin basic protein (MBP) levels, in the cerebrospinal fluid (CSF) of patients with RE was significantly higher than those of patients without RE (P = 0.018, P = 0.026, respectively). CONCLUSIONS: Spinal cord RE is common in patients with NMO. Higher MBP levels in the CSF of patients with RE can be associated with a higher degree of myelin damage.
Assuntos
Neuromielite Óptica/patologia , Medula Espinal/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Gadolínio , Humanos , Aumento da Imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Proteína Básica da Mielina/líquido cefalorraquidiano , Neuromielite Óptica/líquido cefalorraquidiano , Estudos RetrospectivosRESUMO
OBJECTIVES: Parkinson's disease (PD) is a multisystem neurodegenerative disease. We aimed to identify the relationship and factor structure among its different features. MATERIALS & METHODS: Motor, olfactory and cognitive function, and cardiac sympathetic denervation were evaluated in 125 patients with PD using the Unified Parkinson's Disease Rating Scale (UPDRS) part III score, odor stick identification test for the Japanese (OSIT-J), Mini-Mental State Examination (MMSE), and [(123) I] meta-iodobenzylguanidine (MIBG) cardiac scintigraphy (heart-to-mediastinum (H/M) ratio). Pearson's correlation and multiple regression analysis were used to evaluate the association among the four measures with age, gender, and disease duration as the covariates. Exploratory factor analysis was used to identify the underlying factor structure among the measures and covariates. RESULTS: Pearson's correlation and multiple regression analysis showed correlations between OSIT-J score and MIBG H/M ratio, OSIT-J and MMSE scores, UPDRS part III score and MIBG H/M ratio, UPDRS part III score and disease duration, and MMSE score and age. Factor analysis identified three factors: (i) age and MMSE score; (ii) MIBG H/M ratio and OSIT-J score; and (iii) UPDRS part III score and disease duration. CONCLUSIONS: Our results suggest that aging, PD-related pathogenesis, and disease duration underlie the multisystem neurodegeneration present in PD. Moreover, age and disease duration are the major risk factors for cognitive impairment and motor symptoms, respectively. Olfactory impairment and cardiac sympathetic denervation are strongly associated in PD.
Assuntos
Doença de Parkinson/complicações , Doença de Parkinson/fisiopatologia , Fatores Etários , Idade de Início , Idoso , Transtornos Cognitivos/diagnóstico , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
A specific isoform of apolipoprotein E has been associated with the accelerated rate of disease expression of sporadic Alzheimer's disease (AD) and late-onset familial AD (FAD). An earlier age at onset has also been demonstrated in familial AD patients with mutations in the amyloid precursor protein (APP) gene (APP717 and APP670/671)13 carrying the APOE epsilon-4 allele compared to those who do not, but not in familial AD patients with APP692 or 693 mutations, or in chromosome 14-linked familial AD patients. Hypothesizing that receptors for apoE-containing lipoproteins act as a potential risk factor for AD, we performed an association study using a polymorphic triplet (CGG) repeat in the gene for the VLDL receptor (VLDL-R), a receptor for apoE-containing lipoproteins. The frequency of the 5-repeat allele was significantly higher in all of the Japanese sporadic AD patients (P < 0.02) than in the Japanese controls. Moreover, the odds ratio was significantly increased in the AD patients homozygous for the 5-repeat allele (OR = 2.1, 95% CI = [1.1-4.2]). Multiple logistic regression analysis reveals that the relative risk conferred by the presence of two copies of the 5-repeat allele and at least one copy of the APOE epsilon-4 allele is 8.7 (95% CI = [2.9-25.8]). Our results suggest that the VLDL-R gene is a susceptibility gene for AD.
Assuntos
Doença de Alzheimer/genética , Cromossomos Humanos Par 14 , Receptores de LDL/genética , Sequências Repetitivas de Ácido Nucleico , Alelos , Doença de Alzheimer/epidemiologia , Apolipoproteínas E/genética , Sequência de Bases , Córtex Cerebral/metabolismo , Primers do DNA , Humanos , Japão , Dados de Sequência Molecular , Razão de Chances , Reação em Cadeia da Polimerase , Polimorfismo Genético , Valores de Referência , Análise de Regressão , Fatores de RiscoRESUMO
Apoptosis is a key for CD4+ T cell destruction in HIV-1-infected patients. In this study, human peripheral blood lymphocyte (PBL)-transplanted nonobese diabetic (NOD)-severe combined immunodeficient (SCID) (hu-PBL-NOD-SCID) mice were used to examine in vivo apoptosis after HIV-1 infection. As the hu-PBL-NOD-SCID mouse model allowed us to see extensive infection with HIV-1 and to analyze apoptosis in human cells in combination with immunohistological methods, we were able to quantify the number of apoptotic cells with HIV-1 infection. As demonstrated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), massive apoptosis was predominantly observed in virus-uninfected CD4+ T cells in the spleens of HIV-1-infected mice. A combination of TUNEL and immunostaining for death-inducing tumor necrosis factor (TNF) family molecules indicated that the apoptotic cells were frequently found in conjugation with TNF-related apoptosis-inducing ligand (TRAIL)-expressing CD3+CD4+ human T cells. Administration of a neutralizing anti-TRAIL mAb in HIV-1-infected mice markedly inhibited the development of CD4+ T cell apoptosis. These results suggest that a large number of HIV-1-uninfected CD4+ T cells undergo TRAIL-mediated apoptosis in HIV-infected lymphoid organs.
Assuntos
Apoptose/imunologia , Linfócitos T CD4-Positivos/metabolismo , Infecções por HIV/imunologia , HIV-1/imunologia , Glicoproteínas de Membrana/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Anticorpos Monoclonais/farmacologia , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose , Complexo CD3/biossíntese , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Cruzamentos Genéticos , Modelos Animais de Doenças , Sobrevivência de Enxerto , HIV-1/patogenicidade , Humanos , Marcação In Situ das Extremidades Cortadas , Transfusão de Linfócitos , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/farmacologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Baço/metabolismo , Baço/patologia , Baço/virologia , Ligante Indutor de Apoptose Relacionado a TNF , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
OBJECTIVES: To evaluate the association between cerebrospinal fluid (CSF) homovanillic acid (HVA) concentrations and nigrostriatal dopaminergic function assessed by positron emission tomography (PET) imaging with carbon-11-labeled 2beta-carbomethoxy-3beta-(4-fluorophenyl)-tropane ((11)C-CFT), which can measure the dopamine transporter (DAT) density, in Parkinson's disease (PD). METHODS: (11)C-CFT PET scans and CSF examinations were performed on 21 patients with PD, and six patients with non-parkinsonian syndromes (NPS) as a control group. RESULTS: In the PD group, CSF HVA concentrations were significantly correlated with the striatal uptake of (11)C-CFT (r = 0.76, P < 0.01). However, in the NPS group, two indices were within the normal range. CONCLUSIONS: In PD, CSF HVA concentrations correlate with nigrostriatal dopaminergic function. Therefore, CSF HVA concentrations may be an additional surrogate marker for estimating the remaining nigrostriatal dopaminergic function in case that DAT imaging is unavailable.
Assuntos
Gânglios da Base/metabolismo , Dopamina/metabolismo , Ácido Homovanílico/líquido cefalorraquidiano , Doença de Parkinson/líquido cefalorraquidiano , Doença de Parkinson/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Gânglios da Base/diagnóstico por imagem , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Tomografia por Emissão de Pósitrons , Estudos RetrospectivosRESUMO
The patient was a 17-year-old man, who developed Japanese encephalitis in the autumn of 1990 in Japan. He was admitted to our hospital 4 days after onset because of consciousness disturbance. On admission, neurological examination demonstrated left hemiparesis, neck stiffness, and Kernig's sign. He developed generalized tonico-clonic seizure, and required a respirator on the next day of admission. Brain CT 10 days after onset demonstrated hypodensities in the right hippocampus, and the CT obtained 39 days after onset showed whole brain atrophy and hypodensities in the anterior portion of the bilateral thalamus. He died 40 days after onset. Postmortem examination demonstrated perivascular and parenchymal infiltration of lymphocytes and macrophages, proliferation of microglia and astrocytes, and necrosis in the gray matter of the brain. Involvement of the hippocampus and thalamus on CT seemed to reflect the severe lesions characterized by cellular infiltration and necrosis. We discussed for the first time the correlation of CT and neuropathological findings in a patient with Japanese encephalitis.
Assuntos
Encéfalo/diagnóstico por imagem , Encefalite Japonesa/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adolescente , Encéfalo/patologia , Encefalite Japonesa/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Masculino , Necrose/diagnóstico por imagem , Necrose/patologia , Tálamo/diagnóstico por imagem , Tálamo/patologiaRESUMO
To learn about the carboxy-terminal extent of amyloid beta-protein (A beta) composition of senile plaques (SPs) in the brain affected with Alzheimer's disease (AD), we employed two end-specific monoclonal antibodies as immunocytochemical probes: one is specific for A beta 40, the carboxyl terminus of A beta 1-40, while the other is specific for A beta 42(43). In the AD cortex, all SPs that were labeled with an authentic antibody were A beta 42(43) positive, while only one-third of which, on the average, were A beta 40 positive. There was a strong correlation between A beta 40 positivity and mature plaques. Two familial AD cortices with the mutation of beta-amyloid protein precursor 717 (beta APP717) (Val to Ile) showed a remarkable predominance of A beta 42(43)-positive, A beta 40-negative plaques. Diffuse plaques, representing the earliest stage of A beta deposition, were exclusively positive for A beta 42(43), but completely negative for A beta 40.
Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/química , Anticorpos Monoclonais , Encéfalo/metabolismo , Fragmentos de Peptídeos/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Encéfalo/patologia , Córtex Cerebral/química , Córtex Cerebral/metabolismo , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Mutação , Fragmentos de Peptídeos/imunologiaRESUMO
Polyglutamine (polyQ) diseases, such as Huntington's disease and Machado-Joseph disease (MJD), are caused by gain of toxic function of abnormally expanded polyQ tracts. Here, we show that expanded polyQ of ataxin-3 (Q79C), a gene that causes MJD, stimulates Ku70 acetylation, which in turn dissociates the proapoptotic protein Bax from Ku70, thereby promoting Bax activation and subsequent cell death. The Q79C-induced cell death was significantly blocked by Ku70 or Bax-inhibiting peptides (BIPs) designed from Ku70. Furthermore, expression of SIRT1 deacetylase and the addition of a SIRT1 agonist, resveratrol, reduced Q79C toxicity. In contrast, mimicking acetylation of Ku70 abolished the ability of Ku70 to suppress Q79C toxicity. These results indicate that Bax and Ku70 acetylation play important roles in Q79C-induced cell death, and that BIP may be useful in the development of therapeutics for polyQ diseases.
Assuntos
Antígenos Nucleares/metabolismo , Citoproteção/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Peptídeos/farmacologia , Proteína X Associada a bcl-2/antagonistas & inibidores , Acetilação/efeitos dos fármacos , Animais , Caspases/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Histona Acetiltransferases/metabolismo , Humanos , Autoantígeno Ku , Proteínas Mutantes/metabolismo , Peptídeos/toxicidade , Ligação Proteica/efeitos dos fármacos , Conformação Proteica/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Resveratrol , Estilbenos/farmacologia , Vacúolos/efeitos dos fármacos , Vacúolos/metabolismoRESUMO
Recently, nanocarriers that transport bioactive substances to a target site in the body have attracted considerable attention and undergone rapid progression in terms of the state of the art. However, few nanocarriers can enter the brain via a systemic route through the blood-brain barrier (BBB) to efficiently reach neurons. Here we prepare a self-assembled supramolecular nanocarrier with a surface featuring properly configured glucose. The BBB crossing and brain accumulation of this nanocarrier are boosted by the rapid glycaemic increase after fasting and by the putative phenomenon of the highly expressed glucose transporter-1 (GLUT1) in brain capillary endothelial cells migrating from the luminal to the abluminal plasma membrane. The precisely controlled glucose density on the surface of the nanocarrier enables the regulation of its distribution within the brain, and thus is successfully optimized to increase the number of nanocarriers accumulating in neurons.There are only a few examples of nanocarriers that can transport bioactive substances across the blood-brain barrier. Here the authors show that by rapid glycaemic increase the accumulation of a glucosylated nanocarrier in the brain can be controlled.
Assuntos
Glicemia/metabolismo , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Portadores de Fármacos/farmacocinética , Animais , Encéfalo/irrigação sanguínea , Portadores de Fármacos/metabolismo , Feminino , Glucose/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Glicosilação , Humanos , Camundongos Endogâmicos BALB C , Micelas , Microscopia Confocal , Nanopartículas/metabolismo , Neurônios/metabolismo , Polímeros/química , Polímeros/metabolismoRESUMO
The autosomal dominant cerebellar ataxias (ADCAs) comprise a genetically and clinically heterogenous group of neurodegenerative disorders. Very recently, a C-to-T single nucleotide substitution in the puratrophin-1 gene was found to be strongly associated with a form of ADCA linked to chromosome 16q22.1 (16q-linked ADCA; OMIM 600223). We found the C-to-T substitution in the puratrophin-1 gene in 20 patients with ataxia (16 heterozygotes and four homozygotes) and four asymptomatic carriers in 9 of 24 families with an unknown type of ADCA. We also found two cases with 16q-linked ADCA among 43 sporadic patients with late-onset cortical cerebellar atrophy (LCCA). The mean age at onset in the 22 patients was 61.8 years, and that of homozygous patients was lower than that of heterozygous ones in one family. Neurological examination revealed that the majority of our patients showed exaggerated deep tendon reflexes in addition to the cardinal symptom of cerebellar ataxia (100%), and 37.5% of them had sensorineural hearing impairment, whereas sensory axonal neuropathy was absent. The frequency of 16q-linked ADCA was about 1/10 of our series of 110 ADCA families, making it the third most frequent ADCA in Japan.
Assuntos
Ataxia Cerebelar/genética , Cromossomos Humanos Par 16 , Genes Dominantes , Fatores de Troca do Nucleotídeo Guanina/genética , Espectrina/genética , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Ataxia Cerebelar/patologia , Análise Mutacional de DNA/métodos , Saúde da Família , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodosRESUMO
Eosinophilic neurons (ENs) appear in the post-ischemic cortex; however, whether there are differences in the time profile for different cortical layers and the fate of the cortex with ENs is largely unknown. We examined the time profile of ENs in different cortical layers and evolution of cortical atrophy after transient cerebral ischemia in Mongolian gerbils. Unilateral forebrain ischemia was induced twice by 10-minute unilateral common carotid artery occlusions. Brains at 24 hours, 4 days, and 2, 4, and 16 weeks post-ischemia were prepared for morphometric analysis. Quantitative analysis of ENs in regions of interest in the rostral and caudal cortex showed the highest number of ENs at 4 days post-ischemia in layers 3 and 6. Reduction in ENs after this peak was slower in layer 6 than in layer 3 in both rostral and caudal cortex, and this difference was significant in layer 6 of the caudal cortex. Infarcts with significant atrophy appeared in the rostral cortex. In the caudal cortex, only selective neuronal death with mild but distinct atrophy was observed. We observed a significant difference between cortical layers in the time profile of ENs in the post-ischemic cortex. Selective neuronal death without infarction was sufficient to induce cortical atrophy after transient cerebral ischemia.
Assuntos
Isquemia Encefálica/patologia , Córtex Cerebral/patologia , Eosinófilos/patologia , Rede Nervosa/patologia , Neurônios/patologia , Animais , Atrofia , Gerbillinae , Masculino , Fatores de TempoRESUMO
The objective of this study was to establish a rodent model of vascular dementia that showed long-term cognitive and neuropsychological deficits, and to correlate those behavioral deficits with the patterns of ischemic lesions, thus providing a platform for future testing of potential therapeutic agents. In Mongolian gerbils, either 5-minute single bilateral common carotid artery occlusion (SBCCAO) or repetitive bilateral common carotid artery occlusion (two 7-minute occlusions, RBCCAO) was induced, and the behavioral deficits were evaluated using 2 tests: a modified open-field test with an escape zone to evaluate changes in anxiety and locomotor activity, and a T-maze test to assess cognitive dysfunction. SBCCAO did not induce anxiety changes but caused transient locomotor hyperactivity and mild cognitive deficits. Only pyramidal neuronal death was found in the bilateral CA1 sector of the hippocampus following SBCCAO. In contrast, RBCCAO induced persistent locomotor hyperactivity, reduced anxiety, and caused severe cognitive deficits at 4 weeks post-ischemia. RBCCAO caused significant atrophy associated with diffuse selective neuronal death in the bilateral cerebral cortex and caudate nucleus, as well as the CA1 region. The repetitive ischemia model appears to be a potentially useful platform for the long-term analysis of cognitive and neuropsychological symptoms associated with vascular dementia.
Assuntos
Isquemia Encefálica/fisiopatologia , Transtornos Cognitivos/fisiopatologia , Demência/fisiopatologia , Modelos Animais de Doenças , Transtornos Mentais/fisiopatologia , Doenças do Sistema Nervoso/fisiopatologia , Animais , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Demência/diagnóstico , Demência/etiologia , Gerbillinae , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/etiologia , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/etiologiaRESUMO
Antibodies specific for DNA modified by (+/-)-trans-7, 8-dihydrobenzo(a)pyrene-7,8-diol-9, 10-epoxide have been used to quantitate the relative modification level in fragments derived from pBR322 DNA from cellular DNA and in the coding and noncoding strands of simian virus 40 DNA. DNA fragments with a covalent molar modification level ranging from less than 1 to over 200 are resolved by agarose gel electrophoresis and transferred to diazobenzyloxymethyl cellulose paper. The paper is incubated with antibodies specific to carcinogen-modified DNA, and the location of the antibody is visualized by autoradiography after incubation with 125I-protein A. The binding of antibodies is directly proportional to the level of DNA modification. Using this technique, we find that linker DNA is about 2.5- to 3-fold more accessible to (+/-)-trans-7,8-dehydrobenzo(a)pyrene-7, 8-diol-9, 10-epoxide than nucleosomal core DNA and that under in vivo conditions the coding and noncoding strands of the simian virus 40 chromosome are equally accessible to trans-7,8-dihydrobenzo[a]pyrene-7,8-diol-9, 10-epoxide. The approach described allows assessment of the relative level of modification in any DNA sequence which can be subjected to gel electrophoresis.
Assuntos
Benzopirenos/metabolismo , Cromatina/metabolismo , DNA/metabolismo , 7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido , Animais , Linhagem Celular , Fenômenos Químicos , Química , Chlorocebus aethiops , DNA/genética , DNA Viral/genética , DNA Viral/metabolismo , Rim , Plasmídeos , Vírus 40 dos Símios/genéticaRESUMO
antisera against DNA modified with r-7,t-8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDE-1) was elicited in rabbits. Such sera reached with either single- or double-stranded modified DNA but not with unmodified DNA, free benzo(a)pyrene, or proteins modified by BPDE-1. Indirect immunofluorescence studies indicated that the immunoglobulin G in the sera bound specifically to the nuclei of KD cells which were treated with BPDE-1. The intensity of fluorescence was proportional to the dose of BPDE-1 used to treat the cells. About 50% of the BPDE-1-DNA adducts remained bound to DNA 24 hr after the removal of the carcinogen. The location of BPDE-1-modified bases in Col E1 DNA was visualized by immunoelectron microscopy.
Assuntos
Benzopirenos/metabolismo , DNA/metabolismo , 7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido , Especificidade de Anticorpos , Benzopirenos/imunologia , DNA/imunologia , Reparo do DNA , Imunofluorescência , Microscopia EletrônicaRESUMO
Recently it has been shown that the gene-density correlated radial distribution of human 18 and 19 homologous chromosome territories (CTs) is conserved in higher primates in spite of chromosomal rearrangements that occurred during evolution. However, these observations were limited to apes and New World monkey species. In order to provide further evidence for the evolutionary conservation of gene-density-correlated CT arrangements, we extended our previous study to Old World monkeys. They comprise the remaining species group to be analyzed in order to obtain a comprehensive overview of the nuclear topology of human 18 and 19 homologous CTs in higher primates. In the present study we investigated four lymphoblastoid cell lines from three species of Old World monkeys by three-dimensional fluorescence in situ hybridization (3D-FISH): two individuals of Japanese macaque (Macaca fuscata), crab-eating macaque (Macaca fascicularis), and an interspecies hybrid individual between African green monkey (Cercopithecus aethiops) and Patas monkey (Erythrocebus patas). Our data demonstrate that gene-poor human 18 homologous CTs are located preferentially close to the nuclear periphery, whereas gene-dense human 19 homologous CTs are oriented towards the nuclear center in all cell lines analyzed. The gene-density-correlated positioning of human 18 and 19 homologous CTs is evolutionarily conserved throughout all major higher primate lineages, despite chromosomal inversions, fusions, fissions or reciprocal translocations that occurred in the course of evolution in these species. This remarkable preservation of a gene-density-correlated chromatin arrangement gives further support for a functionally relevant higher-order chromatin architecture.
Assuntos
Cromossomos de Mamíferos/genética , Ordem dos Genes/genética , Rearranjo Gênico/genética , Macaca fascicularis/genética , Macaca/genética , Animais , Linhagem Celular , Cromatina/genética , Cromossomos Humanos Par 18/genética , Cromossomos Humanos Par 19/genética , Sequência Conservada/genética , Evolução Molecular , Genes/genética , Humanos , Linfócitos/química , Linfócitos/citologia , Linfócitos/metabolismo , Metáfase/genética , Hibridização de Ácido Nucleico/métodos , Mapeamento Físico do Cromossomo/métodos , Homologia de Sequência do Ácido NucleicoRESUMO
BACKGROUND AND PURPOSE: Predicting response to rtPA is essential in the era of endovascular therapy for stroke. The purpose of this study was to elucidate prognostic factors of early neurologic improvement and long-term outcome with respect to the development and reversion of leptomeningeal collaterals in recanalization therapy after acute ischemic stroke. MATERIALS AND METHODS: We analyzed consecutive patients with proximal MCA occlusion treated with rtPA from 2007 to 2012 at 2 hospital stroke centers. All patients routinely underwent brain MR imaging before rtPA. To assess the reversion of collateral signs, we included patients who underwent follow-up MR imaging. We assessed the development and reversion of collaterals by using a combination of 2 MR imaging collateral markers, the hyperintense vessel sign and the posterior cerebral artery laterality sign. Early neurologic improvement was defined as a decrease in the NIHSS score of ≥10 or a score of ≤2 at 24 hours of treatment. RESULTS: Early neurologic improvement was observed in 22 of 48 eligible patients. The development of collaterals at arrival (15/22 versus 9/26, P = .042) was significantly associated with early neurologic improvement. Multivariate analysis adjusting for other variables showed that the development of collaterals at arrival (OR, 4.82; 95% CI, 1.34-19.98; P = .015) was independently associated with early neurologic improvement. Reversion of collaterals was significantly associated with successful recanalization (P < .001), and multivariate analysis showed that the reversion of collaterals was an independent prognostic factor of long-term functional outcome (OR, 5.07; 95% CI, 1.38-22.09; P = .013). CONCLUSIONS: Our results indicate that the development of leptomeningeal collaterals plays a crucial role in achieving early neurologic improvement, and reversion of collaterals predicts a favorable outcome via arterial recanalization after rtPA treatment for acute stroke.
Assuntos
Encéfalo/irrigação sanguínea , Circulação Colateral/efeitos dos fármacos , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Terapia Trombolítica/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Exame Neurológico/efeitos dos fármacos , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Both cerebral amyloid angiopathy (CAA) and paraoxonase have been reported to be related to lipid metabolism and atherosclerosis. We investigated whether the paraoxonase gene (PON1) polymorphism and atherosclerosis are associated with risk of CAA. METHODS: Associations of the PON1 polymorphism and atherosclerosis of the aorta and coronary and cerebral arteries with the severity of CAA were investigated in 154 elderly Japanese individuals, including 47 patients with Alzheimer's disease. RESULTS: The PON1 polymorphism or severity of atherosclerosis of the arteries was not associated with the severity of CAA. CONCLUSIONS: The PON1 polymorphism and atherosclerosis would not appear to be associated with risk of CAA in the elderly, although further study with larger samples is necessary for confirmation.
Assuntos
Arteriosclerose/enzimologia , Arteriosclerose/genética , Angiopatia Amiloide Cerebral/enzimologia , Angiopatia Amiloide Cerebral/genética , Esterases/genética , Idoso , Idoso de 80 Anos ou mais , Alelos , Doença de Alzheimer/enzimologia , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Aorta/patologia , Arteriosclerose/epidemiologia , Arteriosclerose/patologia , Arildialquilfosfatase , Angiopatia Amiloide Cerebral/epidemiologia , Angiopatia Amiloide Cerebral/patologia , Comorbidade , Frequência do Gene , Genótipo , Heterozigoto , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Lobo Occipital/patologia , Polimorfismo Genético/genética , Medição de Risco , Tamanho da Amostra , Índice de Gravidade de Doença , Estatísticas não ParamétricasRESUMO
"Mounding" is a local contracture of skeletal muscle that is induced by tapping the muscle directly. We studied the mounding phenomenon in vitro on rat muscles that were percussed by a rotating hammer. In the bulged portion of muscle, there were scattered areas where the sarcomere length was shortened. After muscle was depolarized by the application of KCl-Ringer solution or relaxing solution, the mounding phenomenon was preserved. Agents that abolish the function of T-tubule or T-SR junction did not alter the phenomenon, either. However, after the function of intracellular membrane system such as the sarcoplasmic reticulum (SR) was destroyed by Brij 58, the mounding disappeared. Thus, the mounding is a local contracture that is probably induced by calcium ion liberated from the SR by percussion.