RESUMO
The serums of some patients with subacute spongiform encephalopathies contain an autoantibody in higher titer against a normal fibrillar protein within the axon of mature central neurons in culture. The morphological features of this neurofilament, as demonstrated by immunofluorescence and immunoperoxidase staining, and the partial characterization of the antibody are described. The detection of this hetero-specific autoantibody is the first evidence of an immune reaction in the spongiform encephalopathies.
Assuntos
Autoanticorpos/análise , Síndrome de Creutzfeldt-Jakob/imunologia , Citoesqueleto/imunologia , Kuru/imunologia , Especificidade de Anticorpos , Doenças Autoimunes/imunologia , Axônios/imunologia , Imunofluorescência , HumanosRESUMO
Fatal spongiform encephalopathy occurred in four chimpanzees 12 to 14 months after inoculation with suspensions of brain from four patients, respectively. Chimpanzee to chimpanzee transmission was effected without reduction in incubation period. Retransmission of the disease to a second chimpanzee occurred when an inoculum that had been stored at -70 degrees C for over 2 years was used.
Assuntos
Doenças do Sistema Nervoso Central/etiologia , Doenças Transmissíveis/veterinária , Infecções , Animais , Biópsia , Doenças do Sistema Nervoso Central/patologia , Doenças do Sistema Nervoso Central/veterinária , Hominidae , Humanos , Injeções , Pessoa de Meia-IdadeRESUMO
The host range of subacute spongiform virus encephalopathies is described. The asymptomatic incubation period and the duration of the illnesses in various species of animal hosts is discussed along with information on additional species of Old World and New World monkeys and the domestic cat, which have been shown to be susceptible to subacute spongiform virus encephalopathies.
Assuntos
Animais de Laboratório , Encefalopatias/veterinária , Doenças por Vírus Lento/veterinária , Animais , Carnívoros , Gatos , Bovinos , Doenças dos Bovinos , Síndrome de Creutzfeldt-Jakob/veterinária , Cricetinae , Cabras , Cobaias , Haplorrinos , Humanos , Kuru/veterinária , Macaca , Camundongos , Vison , Doenças dos Macacos , Pan troglodytes , Coelhos , Guaxinins , Ratos , Doenças dos Roedores , Scrapie , Ovinos , Doenças dos OvinosRESUMO
In serums of unusually isolated Pacific islanders whose only exposure to influenza occurred during the era of the 1918 pandemic the residual neutralizing antibody was greatest to the PR/8 and BH strains of human type A influenza virus, significantly lower to swine influenza virus, and absent to equine or later human type A virus strains. The pandemic virus was thus antigenically closer to human type A strains isolated during the middle 1930's than to other known influenza virus types.
Assuntos
Antígenos/classificação , Surtos de Doenças/história , Influenza Humana/história , Orthomyxoviridae/imunologia , Animais , História do Século XX , Cavalos , Humanos , Soros Imunes/classificação , Micronésia , Testes de Neutralização , SuínosRESUMO
Four clones were isolated from an adult human brain complementary DNA library with an oligonucleotide probe corresponding to the first 20 amino acids of the beta peptide of brain amyloid from Alzheimer's disease. The open reading frame of the sequenced clone coded for 97 amino acids, including the known amino acid sequence of this polypeptide. The 3.5-kilobase messenger RNA was detected in mammalian brains and human thymus. The gene is highly conserved in evolution and has been mapped to human chromosome 21.
Assuntos
Doença de Alzheimer/genética , Amiloide/genética , Cromossomos Humanos Par 21 , Sequência de Aminoácidos , Clonagem Molecular , DNA/genética , Humanos , Conformação Proteica , RNA Mensageiro/genética , Solubilidade , Transcrição GênicaRESUMO
A human brain cell culture grown in vitro has spontaneously transformed, as determined by morphology, growth characteristics, and karyotype analysis. Virus particles morphologically akin to oncogenic RNA viruses are present in the transformed cells, which are now in subculture 60.
Assuntos
Encéfalo/citologia , Transformação Celular Neoplásica , Vírus Oncogênicos/isolamento & purificação , Vírus de RNA/isolamento & purificação , Encéfalo/microbiologia , Células Cultivadas , Síndrome de Creutzfeldt-Jakob , Humanos , Cariotipagem , Microscopia EletrônicaRESUMO
Clinical signs and pathological changes characteristic of kuru in man and experimental kuru in chimpanzees were observed in two spider monkeys, Ateles geoffreyi, after inoculation with brain tissue from a kuru-affected chimpanzee. The incubation period for one of the monkeys was 23 months, and 26 months for the other.
Assuntos
Hominidae , Kuru/veterinária , Doenças dos Macacos/etiologia , Animais , Encéfalo , Doenças Transmissíveis , Humanos , Doenças dos Macacos/patologia , Fatores de TempoRESUMO
Biopsy material taken from the brain of a patient with CreutzfeldtJakob disease with status spongiosus induced a similar fatal encephalopathy in a chimpanzee 13 months after inoculation.
Assuntos
Doenças dos Animais , Doenças do Sistema Nervoso Central/patologia , Hominidae , Animais , Ataxia , Encéfalo/patologia , Demência , Humanos , Kuru , Masculino , Pessoa de Meia-Idade , MiocloniaRESUMO
Scanning electron microscopy with energy-dispersive x-ray spectrometry was used to analyze the elemental content of neurofibrillary tangle (NFT)-bearing and NFT-free neurons within the Sommer's sector (H1 region) of the hippocampus in Guamanian Chamorros with amyotrophic lateral sclerosis and parkinsonism-dementia and in neurologically normal controls. Preliminary data indicate prominent accumulation of aluminum within the nuclear region and perikaryal cytoplasm of NFT-bearing hippocampal neurons, regardless of the underlying neurological diagnosis. These findings further extend the association between intraneuronal aluminum and NFT formation and support the hypothesis that environmental factors are related to the neurodegenerative changes seen in the Chamorro population.
Assuntos
Alumínio/metabolismo , Tonsila do Cerebelo/patologia , Doença de Parkinson/metabolismo , Idoso , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Demência/complicações , Feminino , Guam , Humanos , Hipotálamo/metabolismo , Masculino , Pessoa de Meia-Idade , Neurofibrilas/metabolismo , Neurônios/metabolismo , Esclerose , Espectrometria por Raios XRESUMO
Scrapie-associated fibrils, first observed in brains of scrapie-infected mice, were also observed in scrapie-infected hamsters and monkeys, in humans with Creutzfeldt-Jakob disease, and in kuru-infected monkeys. These fibrils were not found in a comprehensive series of control brains from humans and animals affected with central nervous system disorders resulting in histopathologies, ultrastructural features, or disease symptoms similar to those of scrapie, kuru, and Creutzfeldt-Jakob disease. These fibrils are also found in preclinical scrapie and in the spleens of scrapie-infected mice; they are a specific marker for the "unconventional" slow virus diseases, and may be the etiological agent.
Assuntos
Doenças por Vírus Lento/patologia , Doença de Alzheimer/patologia , Amiloide/metabolismo , Esclerose Lateral Amiotrófica/patologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/ultraestrutura , Síndrome de Creutzfeldt-Jakob/patologia , Cricetinae , Cuprizona/farmacologia , Humanos , Kuru/patologia , Camundongos , Camundongos Endogâmicos C57BL , Doença de Parkinson/patologia , Saimiri , Scrapie/patologia , Ovinos , Baço/ultraestrutura , Compostos de Trietilestanho/farmacologiaRESUMO
The distribution of cells containing messenger RNA that encodes amyloid beta protein was determined in hippocampi and in various cortical regions from cynomolgus monkeys, normal humans, and patients with Alzheimer's disease by in situ hybridization. Both 35S-labeled RNA antisense and sense probes to amyloid beta protein messenger RNA were used to ensure specific hybridization. Messenger RNA for amyloid beta protein was expressed in a subset of neurons in the prefrontal cortex from monkeys, normal humans, and patients with Alzheimer's disease. This messenger RNA was also present in the neurons of all the hippocampal fields from monkeys, normal humans and, although to a lesser extent in cornu ammonis 1, patients with Alzheimer's disease. The distribution of amyloid beta protein messenger RNA was similar to that of the neurofibrillary tangles of Alzheimer's disease in some regions, but the messenger RNA was also expressed in other neurons that are not usually involved in the pathology of Alzheimer's disease.
Assuntos
Doença de Alzheimer/genética , Amiloide/genética , Encéfalo/fisiopatologia , Peptídeos beta-Amiloides , Animais , Córtex Cerebral/fisiologia , Regulação da Expressão Gênica , Hipocampo/fisiologia , Humanos , Macaca fascicularis , Hibridização de Ácido Nucleico , RNA Mensageiro/genéticaRESUMO
With the recently cloned complementary DNA probe, lambda Am4 for the chromosome 21 gene encoding brain amyloid polypeptide (beta amyloid protein) of Alzheimer's disease, leukocyte DNA from three patients with sporadic Alzheimer's disease and two patients with karyotypically normal Down syndrome was found to contain three copies of this gene. Because a small region of chromosome 21 containing the ets-2 gene is duplicated in patients with Alzheimer's disease, as well as in karyotypically normal Down syndrome, duplication of a subsection of the critical segment of chromosome 21 that is duplicated in Down syndrome may be the genetic defect in Alzheimer's disease.
Assuntos
Doença de Alzheimer/genética , Amiloide/genética , Cromossomos Humanos Par 21 , Síndrome de Down/genética , Família Multigênica , Adulto , Idoso , DNA/genética , Humanos , Leucócitos/análiseRESUMO
Unexplained debilitating dementia or encephalopathy occurs frequently in adults and children with the acquired immune deficiency syndrome (AIDS). Brains from 15 individuals with AIDS and encephalopathy were examined by Southern analysis and in situ hybridization for the presence of human T-cell leukemia (lymphotropic) virus type III (HTLV-III), the virus believed to be the causative agent of AIDS. HTLV-III DNA was detected in the brains of five patients, and viral-specific RNA was detected in four of these. In view of these findings and the recent demonstration of morphologic and genetic relatedness between HTLV-III and visna virus, a lentivirus that causes a chronic degenerative neurologic disease in sheep, HTLV-III should be evaluated further as a possible cause of AIDS encephalopathy.
Assuntos
Encefalopatias/microbiologia , Córtex Cerebral/microbiologia , Deltaretrovirus/isolamento & purificação , Síndrome da Imunodeficiência Adquirida/microbiologia , Adulto , Anticorpos Antivirais/análise , Córtex Cerebral/análise , Criança , Demência/microbiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Hibridização de Ácido Nucleico , RNA Viral/análiseRESUMO
Antibodies reactive with heterologous neural tissue were detected by indirect immunofluorescence microscopy in the sera of 17 of 34 patients with retinitis pigmentosa, one of 30 normal control sera, and a variable percentage of sera derived from subjects with diverse ocular and neurological diseases. These antibodies were also found both in disease-free first degree relatives and in spouses of patients with retinitis pigmentosa. Analytical sodium dodecyl sulfate-polyacrylamide gel electrophoresis of human spinal cord components followed by immunoblots with sera under study revealed that the serum antibody was specific for the high molecular weight protein subunit of neurofilaments. No correlation was found between the presence of these antibodies and other immunological and clinical parameters in retinitis pigmentosa. These findings suggest that release of piled-up neurofilaments from damaged neurones in retinitis pigmentosa triggers B lymphocytes autoreactive to neurofilament antigens.
Assuntos
Anticorpos/análise , Proteínas de Filamentos Intermediários/imunologia , Retinose Pigmentar/imunologia , Adulto , Animais , Especificidade de Anticorpos , Linfócitos B/imunologia , Eletroforese em Gel de Poliacrilamida , Humanos , Imunoglobulinas/análise , Camundongos , Microscopia de Fluorescência , Peso Molecular , Proteínas de Neurofilamentos , Ratos , Medula Espinal/imunologiaRESUMO
To test the possibility that some cases of schizophrenia result from infection with a transmissible slow viral agent, 57 experimental animals (six chimpanzees, 12 Old World monkeys, 17 New World monkeys, and 22 guinea pigs) were inoculated intracerebrally with brain tissue from ten patients and followed up for six years. Behavioral comparisons with control animals revealed no consistent behavioral differences. Histological, immunohistochemical, and morphometric examination of brains of animals that died revealed no specific neuropathological abnormalities. These findings do not support a role for a virus-induced slow infection in the pathogenesis of schizophrenia but must be weighed against methodological limitations in animal susceptibility, disease communicability, and assay sensitivity.
Assuntos
Modelos Animais de Doenças , Tecido Nervoso/transplante , Esquizofrenia/etiologia , Doenças por Vírus Lento/transmissão , Transplante Heterólogo , Adulto , Animais , Comportamento Animal/fisiologia , Encéfalo/microbiologia , Encéfalo/patologia , Feminino , Cobaias , Haplorrinos , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora/fisiologia , Pan troglodytes , Esquizofrenia/microbiologia , Doenças por Vírus Lento/microbiologia , Doenças por Vírus Lento/patologiaRESUMO
Kuru is a subacute neurodegenerative disease presenting with limb ataxia, dysarthria, and a shivering tremor. The disease progress to complete motor and mental incapacity and death within 6 to 24 months. Neuropathologically, a typical pattern of neuronal loss, astrocytic and microglial proliferation, characteristic "kuru-type" amyloid plaques, and PrP deposits in the cerebral cortex and cerebellum are observed. Kuru is the prototype of a group of human transmissible spongiform encephalopathies (TSEs), or "prion" diseases, that include hereditary, sporadic and infectious forms. The latest member of this group, the variant Creutzfeldt-Jakob disease (vCJD), linked to transmission of bovine spongiform encephalopathy (BSE) to humans, shows features similar to kuru. Kuru has emerged at the beginning of the 1900s in a small indigenous population of New-Guinean Eastern Highlands, reached epidemic proportions in the mid-1950s and disappeared progressively in the latter half of the century to complete absence at the end of the 1990s. Early studies made infection, the first etiologic assumption, seem unlikely and led to a hypothesis that kuru might be a genetically determined or genetically mediated illness. After transmissibility of kuru had been discovered and all major epidemiologic phenomena adequately explained by the spread of an infectious agent with long incubation period through the practice of cannibalism, the pattern of occurrence still continued to suggest a role for genetic predisposition. Recent studies indicate that individuals homozygous for Methionine at a polymorphic position 129 of the prion protein were preferentially affected during the kuru epidemic. The carriers of the alternative 129Met/Val and 129Val/Val genotypes had a longer incubation period and thus developed disease at a later age and at a later stage of the epidemic. Observations made during the kuru epidemic are helpful in the understanding of the current vCJD outbreak, and vice versa clinical and experimental data accumulated in studies of other TSE disorders contribute to better understanding of the documented kuru phenomena.
Assuntos
Kuru/genética , Príons/genética , Animais , Bovinos , Síndrome de Creutzfeldt-Jakob/epidemiologia , Síndrome de Creutzfeldt-Jakob/transmissão , Predisposição Genética para Doença , Genótipo , Humanos , Kuru/epidemiologia , Kuru/transmissão , Metionina/genética , Papua Nova Guiné/epidemiologia , Fenótipo , Fatores de RiscoRESUMO
The scrapie amyloid (prion) protein (PrP27-30) is the protease-resistant core of a larger precursor (PrPSc) and a component of the infectious scrapie agent; the potential to form amyloid is a result of posttranslational event or conformational abnormality. The conformation, heat stability, and solvent-induced conformational transitions of PrP27-30 were studied in the solid state in films by CD spectroscopy and correlated with the infectivity of rehydrated and equilibrated films. The exposure of PrP27-30 in films to 60 degrees C, 100 degrees C, and 132 degrees C for 30 min did not change the beta-sheet secondary structure; the infectivity slightly diminished at 132 degrees C and correlated with a decreased solubility of PrP27-30 in sodium dodecyl sulfate (SDS), probably due to cross-linking. Exposing PrP27-30 films to formic acid (FA), trifluoroacetic acid (TFA), trifluoroethanol (TFE), hexafluoro-2-propanol (HFIP), and SDS transformed the amide CD band, diminished the mean residue ellipticity of aromatic bands, and inactivated scrapie infectivity. The convex constraint algorithm (CAA) deconvolution of the CD spectra of the solvent-exposed and rehydrated solid state PrP27-30 identified five common spectral components. The loss of infectivity quantitatively correlated with a decreasing proportion of native, beta-pleated sheet-like secondary structure component, an increasing amount of alpha-helical component, and an increasingly disordered tertiary structure. The results demonstrate the unusual thermal stability of the beta-sheet secondary structure of PrP27-30 protein in the solid state. The conformational perturbations of PrP27-30 parallel the changes in infectivity and suggest that the beta-sheet structure plays a key role in the physical stability of scrapie amyloid and in the ability to propagate and replicate scrapie.
Assuntos
Príons/química , Príons/patogenicidade , Scrapie/etiologia , Algoritmos , Animais , Bioensaio , Dicroísmo Circular , Cricetinae , Temperatura Alta , Mesocricetus , Proteína PrP 27-30 , Proteínas PrPSc , Desnaturação Proteica , Estrutura Secundária de Proteína , Solventes , Espectrofotometria UltravioletaRESUMO
The antineurofilament antibodies found in the serum of a chimpanzee with experimental Creutzfeldt-Jakob disease reacted specifically with the 200,000-dalton polypeptide of the purified neurofilament triplet. They also reacted strongly with thoroughly characterized neurofilament swellings of proximal axons of spinal cord motoneurons from beta,beta' iminodipropionitrile (IDPN)-intoxicated rats.
Assuntos
Autoanticorpos/análise , Síndrome de Creutzfeldt-Jakob/imunologia , Citoesqueleto/imunologia , Animais , Síndrome de Creutzfeldt-Jakob/patologia , Citoesqueleto/patologia , Humanos , Ratos , Ratos Endogâmicos , Medula Espinal/patologiaRESUMO
Creutzfeldt-Jakob disease and kuru were studied in experimental primates. Eight animals with clinical disease lasting from 1/2 to 12 1/2 months were evaluated for histological evidence of progression of the pathological triad of neuronal vacuolation, neuronal loss and fibrous astrocytosis. The first change to appear was neuronal vacuolation, in both the body of neurones and in the neuropil. Fibrous astrocytosis was found subsequent to neuronal damage and necrosis. Neuronal loss was apparent when clinical signs were present. As the clinical disease progressed, so did the severity of neuronal loss and astrocytosis. Five animals, 1 1/2-10 1/2 months after intracerebral inoculation, before they had shown any signs of clinical disease, had histological evidence of neuronal vacuolation and astrocytosis.
Assuntos
Encéfalo/patologia , Síndrome de Creutzfeldt-Jakob/patologia , Kuru/patologia , Animais , Astrócitos/patologia , Tronco Encefálico/patologia , Cerebelo/patologia , Córtex Cerebral/patologia , Corpo Estriado/patologia , Modelos Animais de Doenças , Haplorrinos , Hipocampo/patologia , Humanos , Neurônios/patologia , Primatas , Fatores de TempoRESUMO
We examined 50 patients with parkinsonism-dementia complex of Guam (Guam PDC), 10 Guamanian patients with amyotrophic lateral sclerosis (ALS), 5 patients with combined PDC and ALS (PDC-ALS), and 20 non-PDC non-ALS Guamanians, who had been autopsied between 1979 and 1982, paying special attention to glial inclusions. Gallyas-positive and tau-immunopositive intracytoplasmic inclusions were observed in many of the glial cells, in addition to extensive neurofibrillary tangles (NFTs) in the brains of Guam PDC and PDC-ALS patients. Granular hazy inclusions were seen in the astrocytes, and some crescent/coiled inclusions were observed in the oligodendroglia. Many granular hazy inclusions were observed in the amygdaloid nucleus, inferior olivary nucleus, and lateral funiculus of the spinal cord. The crescent/coiled inclusions were observed predominantly in the anterior nucleus of the thalamus, motor cortex, midbrain tegmentum, pyramids of the medulla oblongata, and lateral funiculus of the spinal cord. The granular hazy inclusions have never been reported previously, and the topographic distribution of the crescent/coiled inclusions in Guam PDC and PDC-ALS differs from those reported previously in other NFT-forming diseases. These findings indicate that Guam PDC and PDC-ALS involve not only neurons but also glia, and that their morphological and topographic differences from other NFT-forming diseases may provide further insights into their distinct etiopathogenesis, and thus prove useful for diagnosis.