RESUMO
Congenital nuclear cataracts transmitted by an autosomal dominant gene are present in a line of strain 13/N guinea-pigs. Studies on the lens proteins from these animals demonstrate changes in both the composition and structure of the crystallins relative to normal controls. The most prominent difference is in the zeta-crystallin, a taxon-specific crystallin which has been shown to be related to the alcohol dehydrogenases. In animals homozygous for the cataract phenotype the normal zeta-crystallin polypeptide is absent from the lens. Quantitation is difficult in the cataractous lenses from heterozygotes because of protein changes secondary to opacification: however in liver and kidney which have catalytic levels of the protein, the concentrations are approximately half that present in tissue from normal control animals. These findings suggest that in the cataractous animals a mutation has occurred in the gene for zeta-crystallin. In addition, a novel protein which is very similar to zeta-crystallin is synthesized only in the lenses of animals with cataract. This protein appears to be the product of the mutant gene for zeta-crystallin. These data support the hypothesis that this hereditary congenital cataract results from a specific mutation in the zeta-crystallin gene.
Assuntos
Catarata/genética , Cristalinas/genética , Mutação , Animais , Catarata/congênito , Cristalinas/biossíntese , Cobaias , Heterozigoto , Cristalino/metabolismoRESUMO
Lens proteins from the guinea pig (Cavia porcellus) were found to be similar to those of other mammals with the exception of the presence of a previously undescribed constituent comprising about 10% of the total soluble lens proteins. This oligomeric protein is composed of polypeptides with apparent molecular weight of 38,000 and elutes from gel exclusion chromatography columns in the beta H-crystallin fraction. Following purification by ion exchange chromatography an antibody was raised against the protein. Using that antibody and antibodies specific for other crystallins we could detect no cross-reactivity between the guinea pig protein and any other reported lens crystallin. This protein, which we have named zeta (zeta)-crystallin, is the first reported mammalian lens crystallin which is not part of the alpha- or beta-gamma families of crystallins. Unlike all other known mammalian crystallins, which have little or no alpha-helical structure, zeta-crystallin is estimated to be approximately 30-40% alpha-helix.
Assuntos
Cristalinas/metabolismo , Cobaias/metabolismo , Animais , Fenômenos Químicos , Química , Cromatografia por Troca Iônica , Reações Cruzadas , Eletroforese em Gel de PoliacrilamidaRESUMO
Experimental autoimmune encephalomyelitis (EAE) and/or tuberculin sensitivity were transferred to histocompatible recipients with myelin basic protein-stimulated and/or PPD stimulated guinea pig lymph node T cells previously separated by depletion of B cells ("panning") on rabbit anti-guinea pig Ig antibody-coated Petri plates. The depletion was augmented by complement-mediated lysis using mouse anti-guinea pig B-cell monoclonal antibody (31D2), rabbit anti-mouse Ig, and rabbit complement. B cells did not transfer EAE nor provide protection against active immunization with guinea pig spinal cord antigen.
Assuntos
Encefalomielite Autoimune Experimental/imunologia , Imunização Passiva , Linfócitos T/imunologia , Animais , Anticorpos Monoclonais/imunologia , Cobaias , Linfonodos/imunologia , Masculino , Proteína Básica da Mielina/farmacologia , Fatores de TempoRESUMO
The pathology of experimental allergic encephalomyelitis (EAE) induced by bovine myelin basic protein (MBP) has been examined in the guinea pig with a series of doses ranging from 37.5 micrograms to 600 micrograms. This was to investigate whether the previously demonstrated lack of demyelinative effect by MBP was dose-related. At all doses tested, MBP induced clinical disease. Inflammation was the major feature of lesions in all animals. However, no demyelination was seen when 75 micrograms MBP or less was given. At higher doses (150 micrograms upwards), MBP always induced intense inflammation but demyelination was encountered inconsistently. These observations support the contention that in addition to an immune response to MBP, other factors contribute to autoimmune demyelination.
Assuntos
Encefalomielite Autoimune Experimental/etiologia , Proteína Básica da Mielina/administração & dosagem , Animais , Autoanticorpos/análise , Relação Dose-Resposta Imunológica , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Feminino , Galactosilceramidas/imunologia , Cobaias , Inflamação , Proteína Básica da Mielina/imunologia , Bainha de Mielina/patologiaRESUMO
Severe (24/24) and lethal (22/24) autoimmune encephalomyelitis was regularly induced in rhesus monkeys of all age groups from newborns to adults by a single injection of guinea pig spinal cord in complete Freund's adjuvant. Age dependency of the encephalomyelitis was manifested by a delayed onset and prolonged course in newborn monkeys. A hemorrhagic retinopathy usually accompanying the earliest CNS symptoms was observed in most of these monkeys. The most severe lesions were predominant in the cerebellum and brainstem of neonates, and in the cerebral hemispheres of older animals.
Assuntos
Encefalomielite Autoimune Experimental/fisiopatologia , Hemorragia Retiniana/fisiopatologia , Fatores Etários , Animais , Sistema Nervoso Central/patologia , Encefalomielite Autoimune Experimental/complicações , Encefalomielite Autoimune Experimental/embriologia , Encefalomielite Autoimune Experimental/imunologia , Feto/imunologia , Idade Gestacional , Cobaias/imunologia , Macaca mulatta , Bainha de Mielina/fisiologia , Hemorragia Retiniana/etiologia , Hemorragia Retiniana/imunologia , Medula Espinal/imunologiaRESUMO
A spontaneous nuclear cataract seen in strain 13 guinea pigs was inherited under circumstances compatible with it being due to an autosomal dominant gene. This animal model seems advantageous for studies in embryology, developmental neurology, and genetics.
Assuntos
Catarata/genética , Cobaias/genética , Animais , Catarata/congênito , Genes Dominantes , Modelos BiológicosRESUMO
Bilateral cataracts observed in the eyes of a 13/N guinea pig and one of her two offspring led to studies to determine the nature of this cataract and its possible heritability. The cataract was determined to be of the nuclear type, was congenital, and apparently transmitted by a single autosomal dominant gene. The cataractous condition of the mother had no effect on the percentage of litters containing stillborns. The cataractous condition of the offspring had no effect on their viability in utero, i.e., there was no greater incidence of stillborns among cataractous than among non-cataractous offspring. The birthweights of the cataractous animals were lower, but not significantly, than those of their non-cataractous littermates; however, the survivability to weaning of the cataractous offspring was reduced significantly when compared to their non-cataractous siblings.
Assuntos
Catarata/veterinária , Genes Dominantes , Animais , Peso ao Nascer , Catarata/congênito , Catarata/genética , Cruzamentos Genéticos , Feminino , Morte Fetal/veterinária , Cobaias/genética , Tamanho da Ninhada de Vivíparos , Masculino , Mortalidade , GravidezRESUMO
In immature Strain 13 guinea pigs sensitized to syngeneic spinal cord, a chronic allergic encephalomyelitis is elicited reminiscent of demyelinating diseases of man and which features relapses or progressive downhill course and extensive areas of demyelination in the central nervous system. However, juvenile recipients of syngeneic lymphocytes from similarly sensitized juveniles show only the acute form of experimental allergic encephalomyelitis. Neuropathologically, the CNS of affected animals displayed mild changes only and minimal demyelination. These observations indicate that the age-dependent differences seen between the acute disease of adults and the chronic disease of juveniles may be due to differences in availability of modulating or reparatory factors, rather than differences in the central nervous system organ or in the immune response itself.
Assuntos
Encefalomielite Autoimune Experimental/imunologia , Cobaias/fisiologia , Imunização Passiva , Doença Aguda , Animais , Sistema Nervoso Central/patologia , Doença Crônica , Encefalomielite Autoimune Experimental/patologia , Encefalomielite Autoimune Experimental/transmissão , Humanos , Doadores de TecidosRESUMO
Experimental autoimmune (allergic) encephalomyelitis (EAE) was induced in Strain 2 guinea pigs, a strain usually regarded as resistant to EAE. The development of disease in groups of juvenile male or female Strain 2/N guinea pigs was irregular with clinical EAE manifesting only in some groups of females. All animals examined morphologically (12 females and 9 males), between 3 and 18 months postinoculation, showed extensive changes in the central nervous system, although 12 of these had displayed no neurologic signs. This silent central nervous system disease, reminiscent of similar phenomena in man, indicates that Strain 2/N is fully competent immunologically at the level of the target organ.
Assuntos
Sistema Nervoso Central/patologia , Encefalomielite Autoimune Experimental/imunologia , Animais , Encefalomielite Autoimune Experimental/patologia , Feminino , Cobaias , Masculino , Microscopia Eletrônica , Bainha de Mielina/patologia , Fatores Sexuais , Medula Espinal/patologia , Medula Espinal/ultraestrutura , Linfócitos T/imunologiaRESUMO
Preliminary results are presented on the treatment of Strain 13 guinea pigs with chronic relapsing experimental autoimmune (allergic) encephalomyelitis (EAE) induced by a single sensitisation with whole spinal cord. Animals were treated at different stages of the disease with injection containing either myelin basic protein (MBP) alone in incomplete Freund's adjuvant (IFA), or MBP in combination with a lipid hapten of myelin, galactocerebroside (GC) in IFA. The rationale for this treatment stemmed from previous work which suggested that MBP was responsible for T cell sensitisation in EAE and that GC was important in producing demyelinating antibodies and that both myelin components were needed in the induction of disease. Although treatment with MBP alone caused some initial stabilisation of the disease process, subsequent relapses occurred in all animals. However, in animals given MBP and GC together, either early or late in the course of the disease, marked clinical improvement has been noted with little or no development of relapses over an observation period of more than one year post-treatment. In addition, evidence of extensive remyelination and oligodendroglial proliferation in CNS lesions has been found in MBP-GC-treated animals suggesting that this therapy might be beneficial for CNS repair and relevant to multiple sclerosis.
Assuntos
Encefalomielite Autoimune Experimental/terapia , Proteína Básica da Mielina/uso terapêutico , Medula Espinal/patologia , Animais , Doença Crônica , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/patologia , Galactosilceramidas/uso terapêutico , Cobaias , Haptenos , Imunoterapia , Masculino , Medula Espinal/imunologiaAssuntos
Encéfalo/imunologia , Encefalomielite Autoimune Experimental/imunologia , Medula Espinal/imunologia , Animais , Linfócitos B , Separação Celular , Complemento C3/análise , Cobaias , Imunoglobulina G/análise , Macrófagos , Masculino , Meninges/imunologia , Proteína Básica da Mielina/farmacologia , Linfócitos TAssuntos
Linfócitos B/patologia , Sistema Nervoso Central/patologia , Encefalomielite Autoimune Experimental/patologia , Linfócitos T/patologia , Animais , Linfócitos B/imunologia , Movimento Celular , Sistema Nervoso Central/imunologia , Encefalomielite Autoimune Experimental/imunologia , Imunofluorescência , Cobaias , Masculino , Linfócitos T/imunologiaRESUMO
Optic nerve tissue from strain 13 guinea pigs sensitized for chronic (relapsing) experimental allergic encephalomyelitis has been examined up to 3 years postinoculation. The changes were compared with the clinical history in each case, with lesions occurring elsewhere in the central nervous system and with optic nerve tissue from a single case of chronic multiple sclerosis. In chronic experimental allergic encephalomyelitis was found that optic neuritis was a consistent finding. Active lesions in the optic nerve were a feature of animals sampled up to 4 months postinoculation. Unlike lesions in the spinal cord, changes occurring in long term animals did not parallel clinical signs. The absence of active lesions in long term animals was apparently not due to a resistance to recurrent disease on the part of the tissue since a second challenge with central nervour system tissue was capable of producing active inflammation in the optic nerve. It appears, therefore, that in its unmanipulated state, chronic experimental allergic encephalomyelitis is more a disease of the spinal cord. Optic nerve changes in the case of multiple sclerosis did not compare well with the guinea pit lesions--discrepancies which we speculate as being related to differences in anatomy, age, species, and longevity of the disease process (among others), rather than a difference in pathogenesis.
Assuntos
Encefalomielite Autoimune Experimental/complicações , Esclerose Múltipla/complicações , Neurite Óptica/complicações , Animais , Doença Crônica , Encefalomielite Autoimune Experimental/patologia , Cobaias , Humanos , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , Bainha de Mielina/patologia , Neurite Óptica/patologia , Fatores de TempoRESUMO
Groups of juvenile Strain 13 guinea pigs sensitized for chronic relapsing experimental allergic encephalomyelitis (EAE) with isogeneic central nervous system (CNS) tissue in complete Freund's adjuvant (CFA) were either left to develop late-onset chronic EAE (unsuppressed), or given a series of injections of bovine myelin basic protein (MBP) in incomplete Freund's adjuvant (IFA) to suppress the disease. All unsuppressed animals developed disease and all suppressed animals remained healthy over a 27-month period of study. some unsuppressed and suppressed animals were rechallenged with CNS tissue in CFA 12 or 26 months post-inoculation (PI). Unsuppressed animals all became sick 2-4 weeks after rechallenge, while rechallenged, suppressed animals were protected, indicating that the suppression was permanent. Pathologic findings in the CNS complemented the clinical changes. Circulating lymphocyte studies were performed on animals from all groups. Early (active, high-affinity rosetting) T cell levels in unsuppressed animals showed significant decreases during exacerbations (P less than 0.01) and normal values during remissions. After rechallenge, circulating early T cells decreased in unsuppressed animals with the development of signs. In suppressed animals, early T cells showed significant elevations during, and for a short time after, the period of suppressive injections, and normal values afterwards. These levels did not change significantly after rechallenge. Late (total, 24 hour rosetting) T cell and B cell values showed minor fluctuations only which did not correlate with disease activity. These results indicate that chronic relapsing EAE can be successfully suppressed with MBP in IFA, that this suppression is permanent and that the immunologic findings presented correlate well with the clinical and pathologic facets of the disease. the findings are presented in terms of their relevance to multiple sclerosis.
Assuntos
Encefalomielite Autoimune Experimental/patologia , Adjuvante de Freund/farmacologia , Contagem de Leucócitos , Linfócitos/imunologia , Proteína Básica da Mielina/farmacologia , Animais , Doença Crônica , Doenças Desmielinizantes/patologia , Encefalomielite Autoimune Experimental/imunologia , Cobaias , Masculino , Medula Espinal/patologiaRESUMO
The formation of fibrotic bridges from subpial astrocytes into the subarachnoid space of the spinal cord and the migration of Schwann cells to the central nervous system (C.N.S.) is appraised in chronically demyelinated C.N.S. lesions. Spinal cord tissue was studied from inbred, Strain 13 guinea pigs with chronic experimental allergic encephalomyelitis (EAE). It has been found that uncommitted Schwann cells are present around remyelinated fibres in nerve root entry zones, between meningeal cells at a distance from the roots and along blood vessels within the spinal cord parenchyma. It is speculated that these cells migrate via the above route to the C.N.S. In the present model, this invasion might be aided by glial fibrosis, a process which leads to surface irregularities in the spinal cord, an extensive extracellular space and possible breaches in the glia limitans through which Schwann cells might penetrate.
Assuntos
Astrócitos/patologia , Doenças Desmielinizantes/patologia , Encefalomielite Autoimune Experimental/patologia , Células de Schwann/patologia , Medula Espinal/patologia , Animais , Axônios/patologia , Movimento Celular , Cobaias , Junções Intercelulares/ultraestrutura , Masculino , Bainha de Mielina/patologia , Espaço Subaracnóideo/patologiaRESUMO
The expression of chronic relapsing experimental allergic encephalomyelitis in strain 13 guinea pigs was suppressed with a single series of injections of myelin basic protein in incomplete Freund's adjuvant. The suppression appeared permanent, and subsequent rechallenge with central nervous system antigen failed to elicit exacerbations.
Assuntos
Modelos Animais de Doenças , Encefalomielite Autoimune Experimental/terapia , Esclerose Múltipla/terapia , Proteína Básica da Mielina/uso terapêutico , Animais , Doença Crônica , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Adjuvante de Freund , Cobaias , Imunoterapia , Contagem de Leucócitos , Linfócitos T/imunologiaRESUMO
Central nervous system (CNS) lesion morphology has been studied in inbred Strain 13 guinea pigs sensitized for chronic relapsing EAE in which the disease was either left to develop (unsuppressed) or was suppressed with injections containing myelin basic protein (MBP). Pathologic changes correlated well with clinical activity. In unsuppressed chronic EAE animals, active clinical disease was invariably matched by acute inflammation in the CNS. In more chronic states, the CNS displayed fibrosis and remyelination while relapses showed the CNS to contain recent changes superimposed upon old lesions. In animals in which the disease was suppressed by injections of MBP, clinical signs did not develop. However, some early subclinical changes were seen morphologically. These lesions were able to remyelinate early on and there was no progression in lesion formation. Apparently, therefore, MBP had a beneficial effect upon the course of the disease and had promoted structural repair. It thus appears that MBP therapy might be one effective approach for the prevention of chronic relapsing EAE. The findings should prove relevant to future MBP trials in multiple sclerosis.
Assuntos
Encéfalo/patologia , Encefalomielite Autoimune Experimental/patologia , Animais , Doença Crônica , Encefalomielite Autoimune Experimental/prevenção & controle , Cobaias , Esclerose Múltipla/tratamento farmacológico , Proteínas da Mielina/farmacologia , Proteínas da Mielina/uso terapêuticoRESUMO
Study of lymphocytes from the blood of guinea pigs with acute EAE induced by isologous spinal cord in adjuvant reconfirmed that in comparison to normals, the percentage of early (active or high affinity rosetting) T cells decreases dramatically and that these changes can be correlated with clinical signs. In addition, we have investigated matching samples of CNS infiltrating cells recovered by ultrasonication and have found that coinciding with the decrease in early T cells in the circulation, significantly higher levels (P less than 0.001) of these cells appear within the CNS compartment; It is concluded that the decrease of early T cells in the circulation is caused by their migration to the target organ, the CNS.