RESUMO
OBJECTIVE: A family with neurological findings similar to hereditary sensory and autonomic neuropathy type V having a point mutation in the nerve growth factor beta (NGFB) gene was recently described. The homozygous genotype gives disabling symptoms. The purpose of the present study was to evaluate the symptoms in heterozygous patients. METHODS: 26 patients heterozygous for the NGFB mutation (12 men, mean age 50 (13-90) years) were examined clinically and answered a health status questionnaire, including the Michigan Neuropathy Screening Instrument (MNSI). 28 relatives (15 men, mean age 44 (15-86) years) without the mutation served as controls in the clinical examination part. 23 of the heterozygotes were examined neurophysiologically and six heterozygous patients underwent a sural nerve biopsy. RESULTS: The heterozygous phenotype ranged from eight patients with Charcot arthropathy starting in adult age and associated with variable symptoms of neuropathy but without complete insensitivity to pain, anhidrosis or mental retardation, to 10 symptom free patients. There was no difference in MNSI between the young heterozygous cases (<55 years old) and the controls. Six of 23 heterozygous patients had impaired cutaneous thermal perception and 11 of 23 had signs of carpal tunnel syndrome. Sural nerve biopsies showed a moderate reduction of both small myelinated (Adelta) and unmyelinated (C) fibres. No apparent correlation of small fibre reduction to symptoms was found. CONCLUSIONS: The NGFB mutation in its heterozygous form results in a milder disease than in homozygotes, with a variable clinical picture, ranging from asymptomatic cases to those with Charcot arthropathy appearing in adult age. Particularly age, but perhaps lifestyle factors also, may influence the development of clinical polyneuropathy.
Assuntos
Heterozigoto , Fator de Crescimento Neural/genética , Fenótipo , Mutação Puntual/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 1/genética , Feminino , Neuropatias Hereditárias Sensoriais e Autônomas/genética , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: The diagnosis of cytomegalovirus encephalitis (CMV-E) in AIDS patients is challenging as other illnesses may obscure the symptoms. Here, we characterize the clinical symptoms of CMV-E and link them to post-mortem findings. Patients and methods In 254 homosexual men with AIDS, followed from HIV diagnosis to death before the antiretroviral combination therapy era, CMV-E was suspected in 93 cases. All were CMV-positive in blood. Neurological examination, including cognitive testing was performed in 34 of them within 6 months before death. CMV-E was diagnosed by CMV-PCR in cerebrospinal fluid (n = 24) or by post-mortem (n = 24). RESULTS: The majority complained of forgetfulness (91%), balance difficulties (85%) and impotence (85%). Impaired short-term memory was present in 29 patients. It was extreme in 17, justifying the diagnosis of Korsakoff's syndrome. This was often associated with infectious CMV in blood (P = 0.01). Brainstem symptoms were found in 19 patients. Post-mortem examination often revealed ventriculoencephalitis. CMV was found primarily around the ventricles and in other structures, described in Korsakoff's syndrome. CONCLUSION: The location of CMV in the brain corresponded well to the clinical findings, demonstrating the close relationship between the neurological symptoms and the neuroanatomical lesions.
Assuntos
Síndrome da Imunodeficiência Adquirida/fisiopatologia , Infecções por Citomegalovirus/fisiopatologia , Encefalite Viral/fisiopatologia , Síndrome de Korsakoff/fisiopatologia , Transtornos da Memória/fisiopatologia , Síndrome da Imunodeficiência Adquirida/mortalidade , Síndrome da Imunodeficiência Adquirida/psicologia , Adulto , Comorbidade , Infecções por Citomegalovirus/mortalidade , Infecções por Citomegalovirus/psicologia , Encefalite Viral/mortalidade , Encefalite Viral/psicologia , Humanos , Síndrome de Korsakoff/mortalidade , Síndrome de Korsakoff/psicologia , Masculino , Transtornos da Memória/mortalidade , Transtornos da Memória/psicologia , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Centronuclear myopathy (CNM) is a rare hereditary congenital myopathy characterized by muscular hypotonia and abnormal centralization of nuclei in muscle fibers. The autosomal recessive (AR) form presents from birth to childhood, followed by a mild progression of muscle weakness. Despite recently identified genetic loci in the AR form, genotype-phenotype correlations are poorly established. Our index case is a 17 year old boy with recessive CNM causing loss of ambulation at 13 years of age and requiring ventilatory assistance nightly. Recent genetic testing revealed a c.1723A > T mutation in the BIN1 gene. The phenotype of the index case contrasts to previously published cases, where recessive CNM patients have lost ambulation in their 20s and have not required ventilatory assistance. The disease severity of our index case, carrying a c.1723A > T mutation, widens the phenotypic spectrum of AR CNM to include earlier loss of ambulation and respiratory failure.
Assuntos
Códon sem Sentido , Miopatias Congênitas Estruturais/genética , Proteínas do Tecido Nervoso/genética , Fenótipo , Adolescente , Biópsia por Agulha , Genes Recessivos , Estudos de Associação Genética , Homozigoto , Humanos , Masculino , Músculo Esquelético/patologia , Miopatias Congênitas Estruturais/patologia , LinhagemRESUMO
OBJECTIVES: Homozygous mutations in the HAX1 gene were recently identified in severe congenital neutropenia patients belonging to the original Kostmann family in northern Sweden. Our observations suggested that these patients also develop neurological and neuropsychological symptoms. METHODS: Detailed clinical studies and mutation analyses were performed in the surviving patients belonging to the Kostmann kindred and in two patients not related to this family, along with studies of HAX1 splice variant expression in normal human tissues. RESULTS: Five of six Kostmann family patients and one other patient from northern Sweden harboured homozygous HAX1 mutations (568C-->T, Q190X) and one carried a heterozygous ELA2 gene mutation. One Swedish patient of Kurdish extraction carried alternative homozygous HAX1 mutations (131G-->A, W44X). All the three patients with Q190X mutations who were alive and available for evaluation developed neurological disease with decreased cognitive function, and three of four patients who reached 10 years developed epilepsy. In contrast, the patients with the ELA2 and W44X HAX1 mutations, respectively, showed no obvious neurological abnormalities. Moreover, two alternative HAX1 splice variants were identified in normal human tissues, including the brain. Both transcripts contained exon 5, harbouring the Q190X mutation, whereas the 5' end of exon 2 containing the W44X mutation was spliced out from the second transcript. CONCLUSIONS: We describe neurological and neuropsychological abnormalities for the first time in Kostmann disease patients. These central nervous system symptoms appear to be associated with specific HAX1 mutations.
Assuntos
Doenças do Sistema Nervoso Central/diagnóstico , Neutropenia/congênito , Proteínas/genética , Proteínas Adaptadoras de Transdução de Sinal , Adolescente , Adulto , Doenças do Sistema Nervoso Central/genética , Doenças do Sistema Nervoso Central/imunologia , Análise Mutacional de DNA , Feminino , Homozigoto , Humanos , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Neutropenia/genética , Linhagem , Mutação Puntual , Isoformas de Proteínas , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SuéciaRESUMO
OBJECTIVE: To investigate the effect of the tumour necrosis factor (TNF) blocking agent infliximab in patients with treatment-resistant inflammatory myopathies. METHODS: A total of 13 patients with refractory polymyositis (PM), dermatomyositis (DM), or inclusion body myositis (IBM) were treated with 4 infliximab infusions (5 mg/kg body weight) over 14 weeks. Outcome measures included myositis disease activity score with improvement defined according to The International Myositis Assessment and Clinical Studies Group (IMACS), and MRI. Repeated muscles biopsies were investigated for cellular infiltrates, major histocompatibility complex (MHC) class I and II, TNF, interleukin (IL)1alpha, IL6, high mobility group box chromosomal protein 1 (HMGB-1), interferon gamma (IFNgamma), myxovirus resistance protein A (MxA) and membrane attack complex (MAC) expression. Type I IFN activity was analysed in sera. RESULTS: Nine patients completed the study. Three patients discontinued due to adverse events and one due to a discovered malignancy. Three of the completers improved by >or=20% in three or more variables of the disease activity core set, four were unchanged and two worsened >or=30%. No patient improved in muscle strength by manual muscle test. At baseline, two completers had signs of muscle inflammation by MRI, and five at follow-up. T lymphocytes, macrophages, cytokine expression and MAC deposition in muscle biopsies were still evident after treatment. Type I IFN activity was increased after treatment. CONCLUSIONS: Infliximab treatment was not effective in refractory inflammatory myopathies. In view of radiological and clinical worsening, and activation of the type I IFN system in several cases, infliximab is not an alternative treatment in patients with treatment-resistant myositis.
Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Miosite/tratamento farmacológico , Adulto , Idoso , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Autoanticorpos/sangue , Citocinas/metabolismo , Dermatomiosite/tratamento farmacológico , Dermatomiosite/imunologia , Feminino , Humanos , Infliximab , Interferon gama/metabolismo , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/imunologia , Miosite/imunologia , Miosite de Corpos de Inclusão/tratamento farmacológico , Miosite de Corpos de Inclusão/imunologia , Projetos Piloto , Polimiosite/tratamento farmacológico , Polimiosite/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
The role of antigen-presenting cells (APC) involved in induction of T and B cell mediated autoaggressive immunity in Guillain-Barre syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is poorly understood. We studied the numbers and phenotype of dendritic cells (DC) in blood and cerebrospinal fluid (CSF) over the course of GBS and CIDP before and after immunomodulatory treatment. Four out of seven GBS patients examined prior to treatment with high-dose intravenous immunoglobulins (IvIg) had elevated numbers of CD123(+) plasmacytoid DC in the CSF, while both GBS and CIDP patients examined prior to treatment had elevated numbers of CD11c(+) myeloid DC in the CSF, as compared to patients with noninflammatory neurological diseases (OND). The percentages of blood DC expressing the cell surface marker CD1a, co-stimulatory molecules CD80 and CD86, adhesion molecule CD54, and chemokine receptors CCR1, CCR2, CCR5, and CXCR4 were not affected in GBS or CIDP. The immunohistochemistry of sural nerve biopsies revealed CD11c(+)CD83(-)CD14(-)CD16(-) immature myeloid DC at low numbers, mostly in the perineurium, without difference between CIDP patients and controls. In contrast, the numbers of CD11c(+)CD14(+)/CD16(+) macrophages were higher within the endoneurium in CIDP patients compared with the controls. The recruitment of DC to CSF in GBS and CIDP may be important in capturing antigens released from inflamed spinal nerve roots into CSF and in transferring these antigens from CSF to local lymph nodes, where naive T and B cells may be activated.
Assuntos
Células Dendríticas/imunologia , Células Dendríticas/patologia , Síndrome de Guillain-Barré/líquido cefalorraquidiano , Síndrome de Guillain-Barré/imunologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/líquido cefalorraquidiano , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/imunologia , Nervo Sural/imunologia , Nervo Sural/patologia , Antígenos CD/biossíntese , Antígeno B7-1/biossíntese , Antígeno B7-2 , Antígeno CD11c/biossíntese , Diferenciação Celular/imunologia , Células Dendríticas/metabolismo , Avaliação da Deficiência , Síndrome de Guillain-Barré/sangue , Imuno-Histoquímica , Imunofenotipagem , Molécula 1 de Adesão Intercelular/biossíntese , Subunidade alfa de Receptor de Interleucina-3 , Contagem de Leucócitos , Macrófagos/imunologia , Macrófagos/patologia , Glicoproteínas de Membrana/biossíntese , Células Mieloides/imunologia , Células Mieloides/metabolismo , Células Mieloides/patologia , Doenças do Sistema Nervoso/líquido cefalorraquidiano , Doenças do Sistema Nervoso/imunologia , Doenças do Sistema Nervoso/patologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/sangue , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/fisiopatologia , Receptores de Quimiocinas/biossíntese , Receptores de Interleucina-3/biossíntese , Nervo Sural/metabolismoRESUMO
BACKGROUND: The two widely spread human polyomaviruses, BK virus (BKV) and JC virus (JCV) establish latency in the urinary tract, and can be reactivated in AIDS. JCV might cause progressive multifocal leucoencephalopathy, but although up to 60% of AIDS patients excrete BKV in the urine there have been few reports of BKV-related renal and/or neurological disease in AIDS. OBJECTIVE: To report on an AIDS patient with progressive renal and neurological symptoms involving the retina. DESIGN: Case report. SETTING: Venhälsan, Söder Hospital, Stockholm, Sweden. METHODS: The brain, eye tissue, cerebrospinal fluid, urine and peripheral blood mononuclear cells were analysed by nested PCR for polyoma-virus DNA. Macroscopical and microscopical examination were performed of the kidney and brain post mortem. Immunohistochemical stainings for the two BKV proteins, the VP1 and the agnoprotein, were performed on autopsy material and virus infected tissue culture cells. RESULTS: BKV could be demonstrated in the brain, cerebrospinal fluid, eye tissues, kidneys and peripheral blood mononuclear cells. CONCLUSION: During 6 years, approximately 400 cerebrospinal fluid samples from immunosuppressed individuals with neurological symptoms have been investigated by PCR for the presence of polyomaviruses. BKV DNA has, so far, only been found in the case reported here. Although reports of BKV infections in the nervous system are rare, there is now evidence for its occurrence in immunocompromised patients and the diagnosis should be considered in such patients with neurological symptoms and signs of renal disease. The diagnosis is simple to verify and is important to establish.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Vírus BK/isolamento & purificação , Encefalite Viral/virologia , Nefrite/virologia , Infecções por Papillomavirus/diagnóstico , Retinite/virologia , Infecções Tumorais por Vírus/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Animais , Vírus BK/genética , Encéfalo/patologia , Encéfalo/virologia , DNA Viral/análise , Encefalite Viral/patologia , Humanos , Imuno-Histoquímica , Rim/patologia , Rim/virologia , Masculino , Nefrite/patologia , Infecções por Papillomavirus/virologia , Ratos , Infecções Tumorais por Vírus/virologia , Proteínas Virais/análise , Proteínas Virais Reguladoras e AcessóriasRESUMO
Four patients affected with autosomal dominant cerebellar ataxia, deafness, and narcolepsy underwent brain CT and MRI. Radiologic findings were supratentorial atrophy (more pronounced than infratentorial atrophy), pronounced dilatation of the third ventricle, low T2 signal intensity in the basal ganglia, loss of cerebral cortex-white matter differentiation, and periventricular high-signal rims. 2-[18F]Fluoro-2-deoxy-D-glucose PET was done with one patient, without specific findings. Genetic analyses excluded SCA-1, SCA-2, SCA-3, SCA-6, SCA-7, DRPLA, and huntingtin gene mutations.
Assuntos
Aberrações Cromossômicas/genética , Surdez/genética , Genes Dominantes/genética , Narcolepsia/genética , Degenerações Espinocerebelares/genética , Adolescente , Adulto , Atrofia , Encéfalo/patologia , Transtornos Cromossômicos , Análise Mutacional de DNA , Surdez/diagnóstico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Narcolepsia/diagnóstico , Linhagem , Degenerações Espinocerebelares/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
Partial unilateral deafferentation of the hind limb of rats was carried out by section of the sciatic nerve or the intraneural injection of Ricinus communis agglutinin 1 (RCA I). The development of autotomy was observed over a 6 week period. The axotomized animals autotomized more than those injected with RCA I. A neuroma developed on the proximal stump of the axotomized nerves. Within 7 days the axons of the RCA I-injected nerve degenerated and the cell bodies in dorsal root ganglia L4 and L5 were destroyed. Since the RCA I-injected animals autotomized, it is concluded that purely central factors have a role in the generation of this abnormal behavior. As the axotomized animals autotomized more than the RCA I-treated ones it is further concluded that abnormal impulse activity arising from a neuroma may be an additional factor in causing autotomy.
Assuntos
Lectinas/farmacologia , Degeneração Neural/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos , Lectinas de Plantas , Nervo Isquiático/efeitos dos fármacos , Automutilação/fisiopatologia , Vias Aferentes/fisiopatologia , Animais , Gânglios Espinais/efeitos dos fármacos , Perna (Membro)/inervação , Masculino , Ratos , Ratos Endogâmicos , Nervo Isquiático/cirurgia , Raízes Nervosas Espinhais/efeitos dos fármacosRESUMO
The therapeutic effects of ABR-215062, which is a new immunoregulator derived from Linomide, have been evaluated in experimental autoimmune neuritis (EAN), a CD4(+) T cell-mediated animal model of Guillain-Barré syndrome in man. In previous studies, we reported that Linomide suppressed the clinical EAN and myelin antigen-reactive T and B cell responses. Here EAN induced in Lewis rats by inoculation with peripheral nerve myelin P0 protein peptide 180-199 and Freund's complete adjuvant was strongly suppressed by ABR-215062 administered daily subcutaneously from the day of inoculation. ABR-215062 dose-dependently reduced the incidence of EAN, ameliorated clinical signs and inhibited P0 peptide 180-199-specific T cell responses as well as also the decreased inflammation and demyelination in the peripheral nerves. The suppression of clinical EAN was associated with inhibition of the inflammatory cytokines IFN-gamma and TNF-alpha, as well as the enhancement of anti-inflammatory cytokine IL-4 in lymph node cells and periphery nerve tissues, respectively, in a dose-dependent manner. These effects indicate that ABR-215062 may mediate its effects by regulation of Th1/Th2 cytokine balance and suggest that ABR-215062 is potentially a new chemical entity for effective treatment of autoimmune diseases.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Movimento Celular/efeitos dos fármacos , Hidroxiquinolinas/uso terapêutico , Neurite Autoimune Experimental/prevenção & controle , Nervos Periféricos/imunologia , Nervos Periféricos/patologia , Células Th1/imunologia , Células Th2/imunologia , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacologia , Animais , Movimento Celular/imunologia , Relação Dose-Resposta a Droga , Relação Dose-Resposta Imunológica , Hidroxiquinolinas/química , Hidroxiquinolinas/farmacologia , Injeções Subcutâneas , Interferon gama/biossíntese , Masculino , Neurite Autoimune Experimental/imunologia , Neurite Autoimune Experimental/patologia , Nervos Periféricos/efeitos dos fármacos , Nervos Periféricos/metabolismo , Quinolonas , Ratos , Ratos Endogâmicos Lew , Células Th1/efeitos dos fármacos , Células Th1/metabolismo , Células Th2/efeitos dos fármacos , Células Th2/metabolismo , Fator de Necrose Tumoral alfa/biossínteseRESUMO
The C57BL/6J mice strain is known to be reputedly resistant to induction of experimental autoimmune neuritis (EAN), an animal model of Guillain-Barré syndrome in humans. Here we describe the induction of EAN in mice of the C57BL/6J background by transfer into naive syngeneic recipients bovine peripheral nerve myelin (BPM)-primed donor lymph node cells that had been stimulated in vitro with the bovine peripheral nervous system (PNS) myelin P2 protein peptide 57-81 followed by challenge with BPM, Freund's complete adjuvant and pertussis toxin. EAN was more severe, both clinically and histologically, and accompanied by extensive infiltration of inflammatory cells and demyelination in peripheral nerves when examined on day 30 after transfer of primed T cells from CD4- 8- mice into identical naive hosts than after transfer of cells from primed wild type, CD4-/- or CD8-/- mice to corresponding recipient animals. EAN in CD4-8- mice was also associated with elevated numbers of P2 peptide-reactive interferon-y (TFN-gamma) secreting cells and alphabeta T cells were present in lymph nodes and spleens. The data suggest that PNS myelin activated T cells from an EAN-resistant mice strain are capable of homing to the PNS. The expanded CD4-8- alphabeta T cells may have helper and effector functions, related to initiation of EAN in the CD4-8- mice. Lack of CD4+ and CD8+ expressing cells does not prevent the initiation of an autoimmune disease.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Neurite Autoimune Experimental/genética , Neurite Autoimune Experimental/imunologia , Animais , Autoanticorpos/imunologia , Autoantígenos/imunologia , Linfócitos B/imunologia , Bovinos , Citometria de Fluxo , Adjuvante de Freund/farmacologia , Imunofenotipagem , Linfonodos/citologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína P2 de Mielina/imunologia , Proteína P2 de Mielina/farmacologia , Toxina Pertussis , Polirradiculoneuropatia/imunologia , Nervo Isquiático/imunologia , Nervo Isquiático/patologia , Baço/citologia , Fatores de Virulência de Bordetella/farmacologiaRESUMO
Twenty-nine patients with myositis, including 10 with polymyositis (PM), 6 with dermatomyositis (DM), and 13 with myositis associated with a connective tissue disease (CTD), were followed up for a mean observation time of 49 months. The 13 patients with CTD-associated myositis were further separated by the presence or absence of anti-RNP antibodies. The functional disability at diagnosis was pronounced without differences between the groups. The patients with anti-RNP antibodies did not differ from the other patients regarding initial muscle weakness, erythrocyte sedimentation rate, or creatinine phosphokinase values, but the histopathological muscle changes were generally milder. Rapid improvement of muscle strength on moderate doses of corticosteroids was seen in most patients. At the end of study, corticosteroid treatment had been withdrawn from 17 patients because of remission, including 6 of the 7 patients with anti-RNP antibodies. The presence of electromyographic changes compatible with myositis, pronounced muscle weakness before treatment, and a low erythrocyte sedimentation rate seemed to indicate a less favorable outcome unrelated to diagnostic subgroupings. However, the combination was rarely found among the anti-RNP-positive patients.
Assuntos
Anticorpos/análise , Autoantígenos/imunologia , Miosite/fisiopatologia , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Dermatomiosite/sangue , Dermatomiosite/patologia , Dermatomiosite/fisiopatologia , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Miosite/sangue , Miosite/patologia , Polimiosite/sangue , Polimiosite/patologia , Polimiosite/fisiopatologia , Resultado do Tratamento , Proteínas Centrais de snRNPRESUMO
After a peripheral nerve lesion (rat facial and sciatic) an induction of major histocompatibility complex (MHC) antigens class I was detected immunohistochemically in skeletal muscle fibers and motor neurons. This MHC expression was transient after a nerve crush, when regeneration occurred, but persisted after a nerve cut, when regeneration was prevented. Since the time course of MHC class I expression correlates to that of regeneration a role for this cell surface molecule in regeneration may be considered.
Assuntos
Antígenos de Histocompatibilidade Classe I/metabolismo , Neurônios Motores/imunologia , Músculos/imunologia , Regeneração Nervosa , Traumatismos dos Nervos Periféricos , Animais , Masculino , Neurônios Motores/fisiologia , Músculos/fisiologia , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
Interferon-gamma (IFN-gamma)-like-immunoreactivity was observed in subsets of rat skeletal muscle fibres with 3 different mouse monoclonal antibodies directed to rat IFN-gamma and a rabbit polyclonal anti-rat IFN-gamma-antibody. These strongly IFN-gamma-immunoreactive fibres also expressed antigen defining T-cells of the cytotoxic/suppressor phenotype (CD8) and major histocompatibility complex (MHC) class I antigen.
Assuntos
Antígenos de Diferenciação de Linfócitos T/metabolismo , Regulação da Expressão Gênica , Interferon gama/metabolismo , Músculos/imunologia , Animais , Anticorpos Monoclonais , Imuno-Histoquímica , Masculino , Músculos/metabolismo , Ratos , Ratos EndogâmicosRESUMO
The volume density of mast cells was estimated in nerve end neuromas at various time-points after transection of the left sciatic nerve of 6-week-old mice. After an initial reduction in the amount of mast cells there was a steady increase with numerous cells in 6-month-old neuromas. The variation in amount of mast cells in the individual animals at each time-point was relatively large. Exposure of neuromas to mild trauma resulted in degranulation of mast cells. Possibly, these numerous mast cells, which can liberate their contents after very light touching, may influence the neuroma.
Assuntos
Mastócitos/patologia , Terminações Nervosas/patologia , Neuroma/patologia , Animais , Masculino , Mastócitos/fisiologia , Camundongos , Camundongos Endogâmicos , Terminações Nervosas/fisiologia , Regeneração Nervosa , Neuroma/fisiopatologia , Nervo Isquiático/fisiopatologiaRESUMO
Six FITC-labeled lectins (Con A, WGA, SBA, DBA, UeA 1, PNA) with different carbohydrate specificities were injected into the snout region of 12-day-old mice. WGA, and to a lesser extent Con A, accumulated in trigeminal and facial neurons as a result of somatopetal axonal transport. Only an occasional trigeminal neuron was labeled after injection of SBA and DBA. None of the other lectins were incorporated. WGA and Con A were used for cytophotometric quantification of neuronal accumulation of transported FITC-lectins in isolated neurons from trigeminal ganglia. This technique makes it possible to study changes in neuronal lectin binding sites and adsorptive endocytosis during different physiological and pathological states.
Assuntos
Transporte Axonal , Nervo Facial/metabolismo , Lectinas/metabolismo , Nervo Trigêmeo/metabolismo , Animais , Tronco Encefálico/metabolismo , Endocitose , Camundongos , Camundongos Endogâmicos CBA , Microscopia Eletrônica , Boca/inervaçãoRESUMO
A new autosomal dominant syndrome in a Swedish pedigree is described. Five patients were affected with cerebellar ataxia and sensorineural deafness. Four of these patients had symptoms of narcolepsy. Optic atrophy, other neurological abnormalities and psychiatric symptoms developed with increasing disease duration. Three patients had non-neurological disease in addition, including diabetes mellitus in two and hypertrophic cardiomyopathy in one. Autopsy with neuropathological examination was performed in one case. Molecular studies focused on the short arm of chromosome 6, including the HLA DR2 locus associated with narcolepsy and the (CAG)n repeat at the spinocerebellar ataxia type 1 (SCA1) locus. Biochemical investigation of muscle biopsy of one case indicated mitochondrial dysfunction with selective decrease in ATP production for substrates that normally give the highest rates. The activity of glutamate dehydrogenase was reduced, indicating a low mitochondrial density. We postulate an autosomal dominant genetic factor responsible for this syndrome. Linkage was excluded to HLA DR2, and a normal sized SCA1 repeat was observed. We conclude that a locus predisposing to ataxia, deafness and narcolepsy exists outside this region of chromosome 6.
Assuntos
Surdez/genética , Genes Dominantes , Narcolepsia/genética , Degenerações Espinocerebelares/genética , Adolescente , Sequência de Bases , Feminino , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , LinhagemRESUMO
OBJECTIVE: Polymyositis and dermatomyositis are idiopathic, inflammatory myopathies characterized by proximal muscle fatigue. Conventional immunosuppressive treatment gives a variable response. Biopsies from chronic patients display a low proportion type I and a high proportion of type II muscle fibres. This raised a suspicion that the low proportion of type I fibres might play a role in the muscle fatigue. AIM: To investigate whether the muscle fibre attributes evident in chronic myositis are characteristic for the polymyositis and dermatomyosistis diseases themselves. METHODS: Muscle biopsies were obtained from thigh muscle from untreated patients (n = 18), treated responders (n = 14) and non-responders (n = 6) and from healthy controls (n = 11), respectively. For clinical evaluations, creatine kinase, functional index of myositis and cumulative dose of cortisone were established. RESULTS: Chronic patients had a lower proportion of type I fibres and a higher proportion of type II fibres compared to untreated myositis patients and healthy controls. Fibre cross-sectional area (CSA) did not differ between patients and healthy individuals but all women had a 20% smaller type II fibre CSA compared to men. CONCLUSIONS: Untreated polymyositis and dermatomyositis patients and healthy controls have a different fibre type composition than chronic polymyositis and dermatomyositis patients. Fibre CSA did not differ between healthy controls or any of the patient groups. A low proportion of oxidative muscle fibres can therefore be excluded as a contributing factor causing muscle fatigue at disease onset and the gender difference should be taken into consideration when evaluating fibre CSA in myositis.
Assuntos
Dermatomiosite/patologia , Fibras Musculares de Contração Rápida/patologia , Fibras Musculares de Contração Lenta/patologia , Polimiosite/patologia , Biópsia/métodos , Estudos de Casos e Controles , Doença Crônica , Creatina Quinase/sangue , Dermatomiosite/tratamento farmacológico , Dermatomiosite/enzimologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pacientes , Polimiosite/tratamento farmacológico , Polimiosite/enzimologia , Prednisolona/uso terapêuticoAssuntos
Encefalite/diagnóstico , Herpes Simples/diagnóstico , Doença Aguda , Adulto , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/patologia , Erros de Diagnóstico , Encefalite/diagnóstico por imagem , Encefalite/patologia , Feminino , Humanos , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVES: To determine whether muscle weakness is correlated with inflammation, expression of interleukin 1alpha (IL1alpha) and major histocompatibility complex (MHC) class I and II antigens on muscle fibres. METHODS: Biopsy specimens from clinically symptomatic (proximal muscles) and asymptomatic (all distal but two proximal) muscles in eight patients with polymyositis, three patients with dermatomyositis and six healthy controls were analysed by immunohistochemistry for the presence of T cells and macrophages, and expression of IL1alpha and of MHC class I and II antigens. RESULTS: were evaluated by conventional light microscopy and by computerised image analysis. Results: Inflammatory infiltrates with T cells and macrophages were observed to an equal degree in both symptomatic and asymptomatic muscle. The numbers of capillaries with IL1alpha expression were significantly higher (p<0.05) in the symptomatic and asymptomatic muscles of patients than in controls. The total IL1alpha expression per tissue section assessed by computerised image analysis was significantly higher in symptomatic muscles but not in asymptomatic muscles compared with that in controls. Neither the number of IL1alpha-positive capillaries nor the total IL1alpha expression differed significantly between symptomatic and asymptomatic muscles. Expression of MHC class I and II antigens on muscle fibres was detected in both symptomatic and asymptomatic muscles but rarely in healthy controls. CONCLUSIONS: Presence of inflammatory infiltrates, T cells and macrophages, and expression of MHC class I and II antigens and of IL1alpha on muscle fibres were independent of clinical symptoms, and were present to an equal degree in both proximal and distal muscles. Thus, other factors seem to determine the development of clinical symptoms. One such factor could be variations in physical demands.