RESUMO
Synthetic galactodihydrocerebrosides with widely different fatty acid components can evoke myelination-inhibiting antibodies in rabbits. Whether these are the only such haptens involved in experimental immunizations of other species or in spontaneous human diseases is not yet known.
Assuntos
Reações Antígeno-Anticorpo , Cerebrosídeos/imunologia , Bainha de Mielina/imunologia , Bainha de Mielina/fisiologia , Animais , CoelhosRESUMO
Post-infectious or post-vaccinal demyelinating encephalomyelitis and neuritis may be due to immunological cross-reactions evoked by specific viral antigenic determinants (epitopes) that are homologous to regions in the target myelins of the central and peripheral nervous systems. Such homologies have been found by computer searches in which decapeptides in two human myelin proteins were compared with proteins of viruses known to infect humans. These viruses include measles, Epstein-Barr, influenza A and B, and others that cause upper respiratory infections. Several regions identified in myelin basic protein and P2 protein can be related to experimental allergic encephalomyelitis or neuritis in laboratory animals.
Assuntos
Encefalomielite/metabolismo , Neurite (Inflamação)/metabolismo , Proteínas Virais/genética , Animais , Sequência de Bases , Galinhas , Encefalomielite/etiologia , Encefalomielite/imunologia , Epitopos , Cobaias , Haplorrinos , Humanos , Sarampo/metabolismo , Proteína Básica da Mielina/genética , Proteína P2 de Mielina , Neurite (Inflamação)/etiologia , Neurite (Inflamação)/imunologia , Coelhos , Ratos , Ratos Endogâmicos Lew , Vacinas Virais/efeitos adversos , Vacinas Virais/imunologiaRESUMO
Incubation with specific antigen, myelin basic protein, greatly enhances the ability of guinea pig peritoneal exudate cells to transfer experimental allergic encephalomyelitis. Reproducibly successful transfers are obtained with 10(7) cells. With this relatively small number of cells, in vitro studies to determine the immunologic mechanisms involved in the disease process are now possible.
Assuntos
Líquido Ascítico/citologia , Encefalomielite Autoimune Experimental/transmissão , Animais , Antígenos , Líquido Ascítico/imunologia , Adesão Celular , Divisão Celular , Encefalomielite Autoimune Experimental/imunologia , Exsudatos e Transudatos/imunologia , Cobaias , Imunização Passiva , Masculino , Proteína Básica da Mielina/imunologiaRESUMO
Sensitization of guinea pigs with purified myelin basic protein induces experimental allergic encephalomyelitis (EAE) but does not induce a serum factor which inhibits myelin formation in vitro. This factor, induced by some unidentified constituent of whole central nervous system tissue, should not be characterized as a component of "EAE serum."
Assuntos
Encefalomielite Autoimune Experimental/imunologia , Proteínas do Tecido Nervoso , Animais , Formação de Anticorpos , Reações Antígeno-Anticorpo , Antígenos , Cerebelo/efeitos dos fármacos , Técnicas de Cultura , Doenças Desmielinizantes/imunologia , Cobaias , Soros Imunes/farmacologia , Isótopos de Iodo , Proteína Básica da Mielina , Bainha de Mielina/imunologia , Coelhos/imunologia , Medula Espinal/imunologiaRESUMO
Two basic proteins isolated from bovine white matter in connection with a study of the protein-bound phosphoinositides of central nervous system tisstue have been tested for encephalitogenic activity. The biological activity of these proteins, which is equivalent to that of basic encephalitogenic proteins isolated in other laboratories, suggested that they are identical.
RESUMO
A monoclonal antibody (immunoglobulin G1) has been produced that reacts against myelin basic protein present in or extracted from the brains of many mammals-with certain important exceptions. Because of known species differences in amino acid sequences of basic protein and of certain peptide fragments, the binding site for this particular antibody appeared likely to include residues 130 to 137. Confirmation of this hypothesis was obtained by amino acid composition of the major immunoreactive peptides produced by thermolysin digestion of human basic protein and isolated by high-performance liquid chromatography.
Assuntos
Proteína Básica da Mielina/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais , Bovinos , Galinhas , Epitopos , Cobaias , Humanos , Macaca , Fragmentos de Peptídeos/imunologia , Coelhos , Ratos , Especificidade da EspécieRESUMO
AIMS: The initial aims were to use recently available observations of glioblastomas (as part of a previous study) that had been imaged twice without intervening treatment before receiving radiotherapy in order to obtain quantitative measures of glioma growth and invasion according to a new bio-mathematical model. The results were so interesting as to raise the question whether the degree of radio-sensitivity of each tumour could be estimated by comparing the model-predicted and actual durations of survival and total numbers of glioma cells after radiotherapy. MATERIALS AND METHODS: The gadolinium-enhanced T1-weighted and T2-weighted magnetic resonance imaging volumes were segmented and used to calculate the velocity of radial expansion (v) and the net rates of proliferation (rho) and invasion/dispersal (D) for each patient according to the bio-mathematical model. RESULTS: The ranges of the values of v, D and rho show that glioblastomas, although clustering at the high end of rates, vary widely one from the other. The effects of X-ray therapy varied from patient to patient. About half survived as predicted without treatment, indicating radio-resistance of these tumours. The other half survived up to about twice as long as predicted without treatment and could have had a corresponding loss of glioma cells, indicating some degree of radio-sensitivity. These results approach the historical estimates that radiotherapy can double survival of the average patient with a glioblastoma. CONCLUSIONS: These cases are among the first for which values of v, D and rho have been calculated for glioblastomas. The results constitute a 'proof of principle' by combining our bio-mathematical model for glioma growth and invasion with pre-treatment imaging observations to provide a new tool showing that individual glioblastomas may be identified as having been radio-resistant or radio-sensitive.
Assuntos
Neoplasias Encefálicas/radioterapia , Glioblastoma/radioterapia , Imageamento por Ressonância Magnética , Adulto , Idoso , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Meios de Contraste , Feminino , Glioblastoma/mortalidade , Glioblastoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Carga TumoralRESUMO
New monoclonal antibodies (MAbs) to myelin basic protein (BP) reveal epitopes to be in sequences 22-34, 75-82, 83-96, 118-131 and 125-131. Comparison of these results with those previously reported suggest that almost every sequence of about 10 amino acid residues may be sufficiently antigenic to make a single MAb but that certain regions are immunodominant, strong enough to make practically the same MAb repeatedly. One of these new MAbs (clone 3) has especially interesting reactivity, sharply limited to residues 75-82 in bovine and porcine BP: Lys-Ala-Gln-His-Gly-Arg-Pro. Whales presumably have the same sequence, since their BPs are fully reactive with clone 3 MAb, but all other species of BP, with known sequences of BP, have at least two changes in this sequence. Deletion of Lys75 (as in a tryptic peptide of porcine BP) reduces reactivity with the MAb about 10-fold, whereas substitution of Ala76 by Ser (as in all other species of BP) and either deletion of Gln77 (as in human, monkey and rabbit BP) or His78 (as in the guinea pig and rat BP) or substitution of Pro82 by Thr (as in human, monkey, rat and mouse BP) eliminates reactivity. We speculate that woodchuck and prairie dog BPs in this region closely resemble chicken BP, which has about 2% of the original reactivity. However, squirrel BP is unique, probably having only one of the changes in this region of BP, since it possesses 10-20 times the reactivity of chicken BP but still only 20-50% of the original reactivity with clone 3 MAb, a degree of reactivity not seen with any other species of BP.
Assuntos
Anticorpos Monoclonais/imunologia , Epitopos/análise , Proteína Básica da Mielina/imunologia , Sequência de Aminoácidos , Animais , Especificidade de Anticorpos , Bovinos , Galinhas , Ensaio de Imunoadsorção Enzimática , Cobaias , Humanos , Coelhos , Especificidade da EspécieRESUMO
The major function of a classification of neoplasms is to correlate with prognosis. During the 1980s two trends developed in the classification of gliomas: 1) the presence of necrosis in astrocytomas defines a subset with the worst prognosis (glioblastoma multiforme) and 2) no comparable subset of oligodendroglioma appears to exist, either histologically or prognostically. Even the worst of the oligodendrogliomas has a better prognosis than glioblastomas. These asymmetries must be kept in mind when one is considering the diagnosis of glioblastoma. The absence of a specific stain for oligodendrogliomas, the difficulty in differentiating small anaplastic cells from oligodendroglial cells and the common occurrence of mixtures of normal and/or reactive oligodendroglia and astrocytes in gliomas combine to create potentially confusing misclassification of many gliomas.
Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , Neoplasias Encefálicas/mortalidade , Glioma/mortalidade , Humanos , Necrose/patologia , Análise de SobrevidaRESUMO
So many examples of computer-designed (rather than human-designed) displays occurred at a recent meeting of the American Association of Neuropathologists that we were stimulated to develop simple guides to help improve presentation. Various color combinations provide examples of the best (and worst) contrast between the message and the medium (background).
Assuntos
Apresentação de Dados , Neurologia/métodos , Patologia/métodos , Arte , Cor , CiênciaRESUMO
Guinea pigs with paralysis or other severe neurological signs of experimental allergic encephalomyelitis (EAE) always exhibited typical histological inflammatory lesions. A few animals inoculated with either the encephalitogenic emulsion or only the control adjuvant emulsion had mild weakness or slowness but no histologic lesion. In some instances, these signs were explained by coincidental non-neural disease or trauma. Therefore, such mild clinical signs cannot be considered pathognominic of EAE. Reports from the literature suggesting that animals have developed clinical signs without histological lesions in EAE are considered invalid because of the nonspecificity of clinical signs, the occurrence of intercurrent diseases, the inadequacy or incorrect timing of histologic evaluations, and the lack of controls for specificity of the signs. There is no basis for the supposition that autoimmunity can cause major neurological signs in the absence of inflammatory lesions in the nervous system.
Assuntos
Sistema Nervoso Central/patologia , Encefalomielite Autoimune Experimental/diagnóstico , Animais , Encefalomielite Autoimune Experimental/patologia , Cobaias , MasculinoRESUMO
This paper is a natural three-dimensional extension of a simple two-dimensional mathematical model of glioma growth and diffusion. The model was originally constructed to simulate a case of recurrent anaplastic astrocytoma treated with chemotherapy, and then modified to allow estimation of the effects of the extent of surgical resection and of variations in growth and diffusion to cover the whole range of glioma behavior. Growth is considered to be constant and exponential (analogous to continuously compounding interest) and is expressed as a decimal fraction per day; the diffusion coefficient is expressed as cm2 per day. Model predictions suggest that diffusion, practically ignored until the present, is a more important component of glioma growth than the growth rate. Even with very early diagnosis, only those tumors with a low diffusion coefficient and a rapid growth rate benefit from a wide resection. Surgical resections generally fail, just as dropping fire-fighters into the burned out center of a forest fire fails, the action being on the periphery as the tumor cells or fires spread out from the center.
Assuntos
Glioma/patologia , Astrocitoma/patologia , Divisão Celular , Difusão , Glioma/terapia , Matemática , Modelos TeóricosRESUMO
Mucopolysaccharidosis IIID (MPS IIID) is one of the rarest of the MPS-III syndromes. To date, the clinical manifestations of 10 patients have been reported, the deficient N-acetylglucosamine 6-sulfatase (G6S) enzyme has been purified, and the G6S gene has been cloned, sequenced and localized. However, morphological manifestations of this condition have not been reported and the pathogenesis of the severe neurological deficits remains an enigma. In this paper we describe and correlate the clinical, biochemical and pathological observations for 2 cases of MPS IIID. We used monoclonal antibodies against heparan sulfate (HS) and GM2-ganglioside, thin layer chromatography, mass spectrometry, and morphological techniques to demonstrate the nature and the distribution of the uncatabolized substrates. The majority of the cells in various tissues showed morphological changes expected with lysosomal storage of HS. The central nervous system (CNS) was most severely affected because of the secondary storage of GM2 and GM3 gangliosides in addition to the primary accumulation of HS. The extent as well as the distribution of the diverse storage materials varied within and among different neurons as observed in MPS-III A, B, and C syndromes. This study supports the hypothesis that the neurological dysfunction and neurodegeneration common to the Sanfilippo syndromes is, in part, due to the secondary metabolic perturbations induced by HS accumulation.
Assuntos
Encéfalo/patologia , Mucopolissacaridose III/patologia , Mucopolissacaridose III/fisiopatologia , Adolescente , Autopsia , Química Encefálica , Criança , Pré-Escolar , Feminino , Gangliosídeos/análise , Humanos , Hidrolases/sangue , Leucócitos/enzimologia , Lisossomos/enzimologia , Masculino , Mucopolissacaridose III/sangue , Neurônios/patologia , Neurônios/ultraestruturaRESUMO
We have extended a mathematical model of gliomas based on proliferation and diffusion rates to incorporate the effects of augmented cell motility in white matter as compared to grey matter. Using a detailed mapping of the white and grey matter in the brain developed for a MRI simulator, we have been able to simulate model tumours on an anatomically accurate brain domain. Our simulations show good agreement with clinically observed tumour geometries and suggest paths of submicroscopic tumour invasion not detectable on CT or MRI images. We expect this model to give insight into microscopic and submicroscopic invasion of the human brain by glioma cells. This method gives insight in microscopic and submicroscopic invasion of the human brain by glioma cells. Additionally, the model can be useful in defining expected pathways of invasion by glioma cells and thereby identify regions of the brain on which to focus treatments.
Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , Modelos Biológicos , Invasividade Neoplásica/patologia , Simulação por Computador , Humanos , Imageamento por Ressonância Magnética , Fibras Nervosas/patologia , Neurônios/patologia , Neurônios/ultraestrutura , Lobo Temporal/patologiaRESUMO
We have developed a mathematical model based on proliferation and infiltration of neoplastic cells that allows predictions to be made concerning the life expectancies following various extents of surgical resection of gliomas of all grades of malignancy. The key model parameters are the growth rate and the diffusion rate. These rates were initially derived from analysis of a case of recurrent anaplastic astrocytoma treated by chemotherapies. Numerical simulations allow us to estimate what would have happened to that patient if various extents of surgical resection, rather than chemotherapies, had been used. In each case, the shell of the infiltrating tumour that remains after 'gross total removal' or even a maximal excision continues to grow and regenerates the tumour mass remarkably rapidly. By developing a model that allows the growth and diffusion rates to define the distribution of cells at the time of diagnosis, and then varying these rates by about 50%, we created a hypothetical tumour patient population whose survival times show good agreement with the results recently reported by Kreth for treatments of glioblastomas. Tenfold decreases in the rates of growth and diffusion mimic the results reported by many other investigators with more slowly growing gliomas. Thus, the model quantitatively supports the ideas that (i) gliomas infiltrate so diffusely that they cannot be cured by resection alone, surgical or radiological, no matter how extensive that may be; (ii) the more extensive the resection, regardless of the degree of malignancy of the glioma, the greater the life expectancy; and (iii) measurements of the two rates, growth and diffusion, may be able to predict survival rates better than the current histological estimates of the type and grade of gliomas.
Assuntos
Glioma/patologia , Glioma/cirurgia , Modelos Biológicos , Divisão Celular/fisiologia , Humanos , Processamento de Imagem Assistida por Computador , Recidiva , Procedimentos Cirúrgicos Operatórios/métodos , Análise de SobrevidaRESUMO
During the past two decades computerized tomography (CT) and magnetic resonance imaging (MRI) have permitted the detection of tumours at much earlier stages in their development than was previously possible. In spite of this earlier diagnosis the effects of earlier and more extensive treatments have been difficult to document. This failure has led to an increasing awareness of the importance of infiltration of glioma cells into surrounding grossly normal brain tissue such that recurrence still occurs. In this paper a simple mathematical model for the proliferation and infiltration of such tumours is introduced, based in part on quantitative image analysis of histological sections of a human brain glioma and especially on cross-sectional area/volume measurements of serial CT images while the patient was undergoing chemotherapy. The model parameters were estimated using optimization techniques to give the best fit of the simulated tumour area to the CT scan data. Numerical solution of the model on a two-dimensional domain, which took into account the geometry of the brain and its natural barriers to diffusion, was used to determine the effect of chemotherapy on the spatio-temporal growth of the tumour.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , Divisão Celular/efeitos da radiação , Quimioterapia Adjuvante , Seguimentos , Glioblastoma/radioterapia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Modelos Biológicos , Recidiva Local de Neoplasia/patologia , Tomografia Computadorizada por Raios XRESUMO
The clinical and pathological features of 28 fatal cases of acute uncomplicated massive cerebellar infarction are reviewed. Although infarcts may involve any portion of the cerebellum, they predominantly involve the posteroinferior half of one cerebellar hemisphere. The frequency of acute uncomplicated fatal cerebellar infarction is much greater than previously appreciated, approximating that of acute fatal cerebellar hemorrhage. All patients were past middle age. Atherosclerosis and acute vertebral artery occlusion were the most common etiological factors. The onset was sudden in most cases, with vomiting, dizziness, vertigo, and cerebellar dysfunction. All patients died with progressive brain stem dysfunction and medullary respiratory failure secondary to compression by a swollen cerebellum. Death usually occurred between the third and sixth days following the onset of symptoms, but only six to 30 hours after the onset of obtundation; therefore, decompressive therapy must be instituted promptly.
Assuntos
Cerebelo/irrigação sanguínea , Doença Aguda , Adulto , Idoso , Arteriopatias Oclusivas/complicações , Arteriosclerose/complicações , Hemorragia Cerebral/complicações , Coma/etiologia , Nervos Cranianos/fisiopatologia , Eletroencefalografia , Manifestações Oculares , Feminino , Humanos , Hipertensão/complicações , Infarto/etiologia , Infarto/mortalidade , Infarto/patologia , Masculino , Pessoa de Meia-Idade , Necrose , Respiração , Punção Espinal , Fatores de Tempo , Artéria VertebralRESUMO
Although the human brain stem is considered relatively invulnerable to ischemic anoxia, evaluation of 16 cases of a single acute asphyxial episode either at or following birth indicates that such involvement is a frequent and characteristic aspect of anoxic encephalopathy in the infant. Ischemic cell change, neuronal loss, and nuclear or reticular formation gliosis were present in the brain stem of all but one infant. At least two topographic patterns of anoxic encephalopathy exist: (1) a rostrocaudal pattern of decreasing vulnerability, with the cerebral cortex being most sensitive and the brain stem least sensitive, and (2) a pattern of brain stem and thalamic damage. Of the two, the latter pattern appears to follow most acute asphyxial episodes in the human neonate and infant.
Assuntos
Tronco Encefálico/patologia , Encéfalo/irrigação sanguínea , Hipóxia Encefálica/patologia , Doenças do Recém-Nascido/patologia , Isquemia/patologia , Adolescente , Córtex Cerebral/patologia , Pré-Escolar , Corpo Estriado/patologia , Corpos Geniculados/patologia , Globo Pálido/patologia , Humanos , Lactente , Recém-Nascido , Colículos Inferiores/patologia , Núcleos Talâmicos/patologiaRESUMO
Young rats 6 to 22 days of age are extremely susceptible to the neurotoxic effects of hexachlorophene given as a daily bath of undiluted antiseptic detergent containing 3% hexachlorophene (pHiso-Hex). At this age, most rats are clinically and histologically damaged by as few as two daily baths. Younger rats are relatively resistant, probably because they have less myelin to be affected; older rats cannot be poisoned by this route, probably because the more mature liver excretes the drug more effectively. Age-dose-response curves in rats are similar to those in humans. This experimental model is potentially useful in defining other characteristics of this drug.
Assuntos
Animais Recém-Nascidos , Encefalopatias/induzido quimicamente , Hexaclorofeno/toxicidade , Administração Tópica , Fatores Etários , Animais , Encéfalo/patologia , Encefalopatias/mortalidade , Tronco Encefálico/patologia , Cerebelo/patologia , Relação Dose-Resposta a Droga , Comportamento Exploratório/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Hexaclorofeno/administração & dosagem , Humanos , Recém-Nascido , Doenças do Recém-Nascido/patologia , Microscopia Eletrônica , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/crescimento & desenvolvimento , Bainha de Mielina/patologia , RatosRESUMO
To assess neurotoxic effects of hexachlorophene in the human population previously shown to be most at risk, a blind clinicopathological analysis was made of all premature infants under 1,400 gm birth weight who survived at least four days and were examined by autopsy over a 7.5-year period. Repeated whole-body bathing of premature newborn infants in 3% hexachlorophene-bearing soap (undiluted pHisoHex) shows a significant statistical association with a vacuolar encephalopathy of the brain stem reticular formation. The prevalence of the vacuolar encephalopathy in premature infants on whom we have adequate brain stem histological information appears to be related to the number of exposures to hexachlorophene, the concentration of hexachlorophene, the thoroughness of rinsing, and other factors (including exposure to ultraviolet light).