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2.
Eur J Paediatr Neurol ; 3(3): 119-23, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10461567

RESUMO

Concentrations of the four major brain gangliosides, GM1, GD1a, GD1b and GT1b, biochemical markers of neuronal membranes, were determined in cerebrospinal fluid from a large series of patients with classical Rett syndrome, aged 1.5-21 years at sampling, and from 11 patients with infantile neuronal ceroid lipofuscinosis, aged 1.5-11 years. The results were compared with age-matched healthy controls. Compared with fluid from the control group, the cerebrospinal fluid samples from Rett patients contained significantly reduced levels of gangliosides GD1a and GT1b. In cerebrospinal fluid of the infantile neuronal ceroid lipofuscinosis patients, even the very young ones, all four major brain gangliosides were significantly reduced compared with controls and the concentration levels also differed significantly from those in patients with Rett syndrome. The ganglioside pattern in the brain is reflected in the cerebrospinal fluid early in the course of the disease in Rett syndrome and infantile neuronal ceroid lipofuscinosis.


Assuntos
Gangliosídeos/líquido cefalorraquidiano , Lipofuscinoses Ceroides Neuronais/líquido cefalorraquidiano , Síndrome de Rett/líquido cefalorraquidiano , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Diagnóstico Diferencial , Humanos , Lactente , Lipofuscinoses Ceroides Neuronais/diagnóstico , Síndrome de Rett/diagnóstico
3.
Acta Neuropathol ; 94(4): 345-52, 1997 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-9341935

RESUMO

Brain weight, total solids, protein, and major lipids have been determined in 83 female and 101 male brains from subjects 20-100 years of age. The brain weight began to diminish at 20 years of age. The brain weight at 20 years for females: 1,368 +/- 26 and for males 1,632 +/- 27 g diminished at 100 years for females to 1,100 +/- 25 and for males to 1,266 +/- 25 g, a decrease of 20% for female and 22% for male brains. The decrease in dry solids was larger during the same period, 36% for females and males. Proteins decreased by 39% in females and 37% in males. Phospholipids decreased by 42% in females and 43% in males, cholesterol by 47% and 53%, cerebroside by 46% and 58%, sulfatide by 46% and 49% and gangliosides by 28% and 30%, respectively. There is, thus, a significantly larger loss of myelin lipids than of gangliosides-the biochemical marker for neuronal membranes. The loss of myelin lipids was particularly large in female brain after 70 years of age, while the loss in male brain was linear as early as from 20 years of age.


Assuntos
Envelhecimento/metabolismo , Química Encefálica , Encéfalo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Cerebelo/química , Cerebelo/patologia , Feminino , Gangliosídeos/análise , Humanos , Masculino , Lipídeos de Membrana/análise , Pessoa de Meia-Idade , Tamanho do Órgão , Prosencéfalo/química , Prosencéfalo/patologia , Proteínas/análise , Sialoglicoproteínas/análise
4.
Dement Geriatr Cogn Disord ; 8(1): 26-33, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-8997549

RESUMO

We have conducted a preliminary study of the optimum conditions for a therapeutic effect of ganglioside GM1 in Alzheimer's disease. Five patients with the early onset form of Alzheimer's disease (AD type I) received the ganglioside by intracerebroventricular administration for 12 months. Bilateral stereotactic punction of the frontal horns of the ventricular system was performed, and shunt catheters were implanted and connected to a programmable pump. The optimum GM1 dose varied between 20 and 30 mg/24 h. Neurological neuropsychological, psychiatric and neurochemical examinations were performed 7 days before surgery and on days 30, 90, 180 and 360. No patient found the surgery difficult and no patient or relative regretted that they participated in the study. The patients became more active and safer in relation to others and to performance of various activities from day 90. The cerebrospinal fluid level of the monoamine metabolites homovanillic acid and 5-hydroxyindoleacetic acid and the neuropeptide somatostatin increased.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Gangliosídeo G(M1)/uso terapêutico , Idoso , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/psicologia , Circulação Cerebrovascular/fisiologia , Relação Dose-Resposta a Droga , Feminino , Gangliosídeo G(M1)/efeitos adversos , Humanos , Injeções Intraventriculares , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
5.
Int Psychogeriatr ; 8(3): 365-72, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-9116173

RESUMO

Brain tissue from 12 subjects with pure Alzheimer's disease (AD) and 21 subjects with senile dementia of the Alzheimer type (SDAT) was investigated for membrane lipids and compared with that in age-matched controls. In brain tissue from the patients with AD, phospholipids were significantly decreased compared with that from SDAT patients and controls, cholesterol was reduced compared with that in controls, and gangliosides were significantly reduced in all gray-matter areas investigated compared with those in both SDAT subjects and controls. A reduction in gangliosides also occurred in the SDAT group, but it was smaller. In the white matter, the pattern of changes was the opposite. Phospholipids, cholesterol, cerebroside, and sulfatide were significantly reduced in the frontal-lobe white matter in the SDAT group compared with that in age-matched controls and AD patients. Gangliosides in the cerebrospinal fluid also separated AD from SDAT and controls. The findings indicate synapse degeneration as an important pathogenetic factor in AD. This disorder should be separated from SDAT, in which white-matter degeneration appears to be more prominent.


Assuntos
Doença de Alzheimer/patologia , Encéfalo/patologia , Lipídeos de Membrana/metabolismo , Membranas Sinápticas/patologia , Idoso , Idoso de 80 Anos ou mais , Cerebrosídeos/metabolismo , Colesterol/metabolismo , Feminino , Lobo Frontal/patologia , Gangliosídeos/metabolismo , Humanos , Masculino , Fosfolipídeos/metabolismo , Valores de Referência , Sulfoglicoesfingolipídeos/metabolismo
6.
Glycoconj J ; 13(3): 391-9, 1996 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8781970

RESUMO

The human glioma D-54MG cell line grown in vitro primarily expresses ganglio series gangliosides, particularly GM2. Subcutaneous injection of these cells into nude mice produced xenografts with an increased content of the human glioma-associated lacto series gangliosides, primarily 3'-isoLM1, an alteration that was dose dependent, with the highest dose (1 x 10(8)) resulting in a phenotype that was most like that of the inoculum. After one passage in vivo, the lacto series dominated and reached a proportional level that was kept throughout the 10 passages. The mRNA levels of the GM2-synthase clearly coincided with GM2 expression and was 20 times higher in cells grown in vitro than in those grown in vivo. These results support the view that ganglioside expression in human gliomas is strongly influenced by environmental factors.


Assuntos
Gangliosídeo G(M2)/biossíntese , Gangliosídeos/biossíntese , Glioma/metabolismo , N-Acetilgalactosaminiltransferases/biossíntese , Animais , Sequência de Carboidratos , Divisão Celular , Linhagem Celular , Meios de Cultura , Gangliosídeo G(M2)/química , Gangliosídeo G(M2)/isolamento & purificação , Gangliosídeos/química , Gangliosídeos/isolamento & purificação , Glioma/patologia , Humanos , Camundongos , Camundongos Nus , Dados de Sequência Molecular , RNA Mensageiro/análise , RNA Mensageiro/biossíntese , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Transcrição Gênica , Transplante Heterólogo , Células Tumorais Cultivadas , Polipeptídeo N-Acetilgalactosaminiltransferase
7.
Alzheimer Dis Assoc Disord ; 10(2): 77-81, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-8727168

RESUMO

Gangliosides and major membrane components were determined in caudate nucleus, putamen, and hippocampus of 12 cases with Alzheimer disease (AD) type I, also termed presenile or pure AD, and in age-matched controls. The concentration of gangliosides, a marker for axodendritic arborization, was reduced to 71% in caudate nucleus, 82% in putamen, and 66% in hippocampus of that in the controls. Significant diminution of total dry solids, protein, and phospholipids was also found in caudate nucleus and was most pronounced in hippocampus. The early signs of extrapyramidal features have been emphasized in AD type I. We now provide evidence that the neostriatum is affected in AD type I (the putamen, however, to a lesser extent than the caudate nucleus). The biochemical changes in these nuclei can be significantly related to scores of impairment of motor performance.


Assuntos
Doença de Alzheimer/metabolismo , Gânglios da Base/metabolismo , Lipídeos de Membrana/metabolismo , Proteínas de Membrana/metabolismo , Adulto , Idoso , Núcleo Caudado/metabolismo , Feminino , Hipocampo/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Putamen/metabolismo
8.
Acta Paediatr ; 84(7): 787-90, 1995 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-7549298

RESUMO

Concentrations of the four major brain gangliosides, GM1, GD1a, GD1b and GT1b, biochemical markers of neuronal membranes, were determined in the cerebrospinal fluid (CSF) of 20 children with autism and in 25 controls. In addition, the gangliosides were determined in children with different forms of non-progressive neurological disorders lacking clinical features of autism. GM1, GD1a, GD1b and GT1b were significantly increased in patients with autism compared with age-matched controls and children with non-progressive neurological disorders. The gangliosides have previously been shown to have a function in synaptic transmission and increased synaptic activity leads to added release of gangliosides. Our finding of increased CSF levels of gangliosides in autism suggests increased synaptic activity in this disorder.


Assuntos
Transtorno Autístico/líquido cefalorraquidiano , Gangliosídeos/líquido cefalorraquidiano , Adolescente , Fatores Etários , Transtorno Autístico/fisiopatologia , Criança , Pré-Escolar , Cromatografia em Camada Fina , Interpretação Estatística de Dados , Gangliosídeo G(M1)/líquido cefalorraquidiano , Humanos , Deficiência Intelectual/líquido cefalorraquidiano , Deficiência Intelectual/fisiopatologia , Doenças do Sistema Nervoso/líquido cefalorraquidiano , Doenças do Sistema Nervoso/fisiopatologia , Sinapses/fisiologia , Membranas Sinápticas , Transmissão Sináptica
9.
Acta Paediatr ; 84(2): 218-21, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7756815

RESUMO

We describe a male patient with late onset globoid cell leukodystrophy (GLD) (Krabbe's disease) still alive at 24 years of age, with a well preserved intellectual and communicative capacity, in contrast to visual failure and severe central pyramidal and extrapyramidal motor disability with spasticity, dystonia, ataxia and peripheral neuropathy. Visual dysfunction began at 4 years of age, limping and balance problems at 8 years and epilepsy at 14 years of age. Neuroimaging at 15 years of age revealed white matter lesions, and nerve conduction velocity examinations showed a slowly developing polyneuropathy. Galactosylceramidase activity was reduced in leukocytes to 0.07 mu kat/kg protein compared with 0.02 (SD 0.01) mu kat/kg protein in infantile GLD.


Assuntos
Leucodistrofia de Células Globoides , Adulto , Idade de Início , Epilepsia/etiologia , Seguimentos , Galactosilceramidase/sangue , Humanos , Leucodistrofia de Células Globoides/complicações , Leucodistrofia de Células Globoides/diagnóstico por imagem , Leucodistrofia de Células Globoides/enzimologia , Masculino , Equilíbrio Postural , Suécia , Tomografia Computadorizada por Raios X , Transtornos da Visão/etiologia
10.
Acta Psychiatr Scand ; 91(2): 86-94, 1995 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-7778475

RESUMO

Measurements of regional cerebral blood flow (rCBF), analysis of cerebrospinal fluid, auditory brain stem responses (ABR) and oculomotor tests were performed in 19 patients with fibromyalgia. The results from the rCBF measurements showed a normal flow level with slight but significant focal flow decreases in dorsolateral frontal cortical areas of both hemispheres. The ABR results showed signs of dysfunction at least at the brain stem level and the oculomotor tests showed high frequency of pathology. The cerebrospinal fluid analysis showed discrete changes in the cell differential count. Possible explanations for the involvement of the central nervous system in fibromyalgia are discussed.


Assuntos
Fibromialgia/líquido cefalorraquidiano , Fibromialgia/fisiopatologia , Fluxo Sanguíneo Regional , Adulto , Idoso , Albuminas/líquido cefalorraquidiano , Barreira Hematoencefálica , Potenciais Evocados Auditivos do Tronco Encefálico , Feminino , Humanos , Imunoglobulinas/sangue , Imunoglobulinas/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Movimentos Sacádicos , Albumina Sérica/análise
11.
J Neurochem ; 63(5): 1802-11, 1994 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7931336

RESUMO

The membrane lipid composition of human frontal and temporal cortices and white matter has been studied in 118 subjects, age 20-100 years. The brain specimens were selected from subjects who lived a normal social life and died suddenly and unexpectedly with no history of neurologic or psychiatric disease. Macroscopic and microscopic examinations ruled out any signs of organic brain disorder. The sudden death eliminated all risk of changes over a long agonal stage. The data for total solids and major lipids are summarized in graphic form. Total solids, phospholipids, and cholesterol diminished linearly from 20 years of age in frontal and temporal cortices, whereas total solids phospholipids, cholesterol, cerebroside, and sulfatide showed a curvilinear diminution in frontal and temporal white matter. Gangliosides differed from the other lipids, showing an almost constant concentration between 20 and 70 years of age with a slight peak around 50 years of age. The ganglioside pattern showed continuous change with aging, with decreasing proportions of GM1 and GD1a and increasing proportions of GD1b, GM3, and GD3. Equations are given that can be used to calculate the lipid composition of normal human frontal and temporal cortices and white matter at any age between 20 and 100 years of age. These data can be used where data by direct analysis are not available for comparison with values for various pathological states.


Assuntos
Envelhecimento/metabolismo , Química Encefálica , Lobo Frontal/química , Lipídeos de Membrana/análise , Lobo Temporal/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/metabolismo , Córtex Cerebral/química , Córtex Cerebral/metabolismo , Colesterol/análise , Colesterol/metabolismo , Demência Vascular/metabolismo , Lobo Frontal/metabolismo , Gangliosídeos/análise , Gangliosídeos/metabolismo , Humanos , Lipídeos de Membrana/metabolismo , Pessoa de Meia-Idade , Doença de Parkinson/metabolismo , Fosfolipídeos/análise , Fosfolipídeos/metabolismo , Lobo Temporal/metabolismo
12.
Biochim Biophys Acta ; 1214(2): 115-23, 1994 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-7918590

RESUMO

Glycosphingolipids were determined in human spinal cord, cauda equina and femoral nerve of 10 subjects aged 20-70 years and in dorsal and ventral roots of four subjects aged 17-60 years. Myelin was isolated from corresponding tissue. Axons were isolated from the four specimens of dorsal and ventral roots. The concentration (mean and standard error of mean) of gangliosides in spinal cord was 0.80 +/- 0.03 mumol sialic acid/g fresh tissue, in cauda equina 0.40 +/- 0.02 mumol/g and in femoral nerve 0.23 +/- 0.01 mumol/g. In spinal cord only trace amounts of glycosphingolipids of the lacto series were found, and the ganglioside pattern differed from that in cerebral white matter by a relatively high proportion of GD3 and a low proportion of GD1a. The ganglioside patterns were almost identical in cauda equina and femoral nerve--the major ganglioside being 3'-LM1, 0.07 and 0.04 mumol/g respectively. Another ganglioside of the lacto series, 3'-HexLM1, was 25% of 3'-LM1. Peripheral nerve also contained three acidic glycosphingolipids in addition to sulfatide--LK1 and HexLK1 belonging to the glycosphingolipid lacto series and containing glucuronyl-3-sulfate instead of sialic acid, and inositolphosphoryl galactosylceramide. The dorsal (sensory) and ventral (motor) roots had the same major membrane lipid composition but the ganglioside concentration was 30% higher in sensory than motor nerve and myelin. The patterns of gangliotetraose gangliosides were, however, the same in motor and sensory myelin and axons. The ceramide composition of the gangliosides is also reported.


Assuntos
Ceramidas/química , Gangliosídeos/análise , Glicoesfingolipídeos/análise , Nervos Periféricos/química , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Carboidratos , Ceramidas/análise , Gangliosídeos/isolamento & purificação , Humanos , Pessoa de Meia-Idade , Dados de Sequência Molecular , Proteínas da Mielina/análise
13.
J Neurochem ; 62(3): 1039-47, 1994 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8113790

RESUMO

Major membrane lipids were quantified in frontal (Brodmann area 9) and temporal (Brodmann areas 21 and 22) cortices, caudate nucleus, hippocampus, and frontal white matter of 12 cases with Alzheimer's disease (AD) type I (early onset), 21 cases with AD type II (late onset), and 20 age-matched controls. The concentration of gangliosides--a marker for axodendritic arborization--was reduced to 58-70% of the control concentration in all four gray areas (p < 0.0001) and to 81% in frontal white matter (p < 0.01) of AD type I cases, whereas it was only significantly reduced in temporal cortex (p < 0.01), hippocampus (p < 0.05), and frontal white matter (p < 0.05) in AD type II cases. The concentration of phospholipids was also significantly reduced (p < 0.01-0.0001) in all four gray areas of AD type I cases but in no area of AD type II cases. The loss of cholesterol was only 50% of the corresponding phospholipid diminution in AD type I. These results suggested a pronounced loss of nerve endings in AD type I. The characteristic membrane lipid disturbance in AD type II was a loss of myelin lipids. This is the first time a fundamental biochemical difference has been shown between the two major forms of AD.


Assuntos
Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Encéfalo/metabolismo , Lipídeos de Membrana/metabolismo , Bainha de Mielina/fisiologia , Sinapses/fisiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Gangliosídeos/metabolismo , Humanos , Masculino , Concentração Osmolar , Distribuição Tecidual
14.
Mol Chem Neuropathol ; 21(2-3): 129-38, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7522005

RESUMO

A library of epitope-defined antiganglioside monoclonal antibodies has been used to analyze the ganglioside phenotype of human glioma cell lines, rodent xenografts derived from them, and a separate panel of human glioma biopsies by multiple quantitative and qualitative assays. We have shown that the ganglioside phenotypes of cultured cell lines differ from the ganglioside phenotypes in the xenografts grown from the parent lines. The lacto series gangliosides 3'-isoLM1 and 3',6'-isoLD1 are expressed in the majority of primary human central nervous system neoplasms and xenografts derived from glioma cell lines, whereas glioma cell lines themselves express 3'-isoLM1 and 3',6'-isoLD1 in only 2/15 and 0/15 cases, respectively. Examination of the ganglioside profiles of serially passaged xenografts established from the glioma cell line D-54 MG, which does not express the lacto series, revealed the appearance of these gangliosides within one to two passages in vivo. The presence of these defined gangliosides in the majority of human gliomas and their absence in normal brain supports their application in compartmental therapy of primary central nervous system tumors.


Assuntos
Gangliosídeos/metabolismo , Glioma/metabolismo , Animais , Anticorpos Monoclonais , Biópsia , Configuração de Carboidratos , Sequência de Carboidratos , Linhagem Celular , Epitopos/análise , Gangliosídeos/análise , Gangliosídeos/química , Glioma/patologia , Humanos , Camundongos , Camundongos Nus , Dados de Sequência Molecular , Fenótipo , Transplante Heterólogo , Células Tumorais Cultivadas
17.
Int Psychogeriatr ; 6(1): 13-22; discussion 59-60, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-8054491

RESUMO

Ubiquitin (Ub) was determined by a competitive enzyme-linked immunosorbent assay (ELISA) in serum (S) and cerebrospinal fluid (CSF) samples from 29 patients with 'probable Alzheimer's disease' (AD), 14 patients with vascular dementia (VAD), and 13 healthy individuals. The mean concentration of Ub in CSF (110 +/- 20 ng/mL) was about 20% of that in serum (940 +/- 120 ng/mL) in healthy controls. There was no significant correlation between S-Ub and CSF-Ub, or between the CSF/S.Ub ratio and the CSF/S albumin ratio. These findings suggest that a major portion of CSF-Ub is intrathecally produced. CSF-Ub was increased while S-Ub was decreased in both AD and VAD patients as compared with controls. As a consequence, the CSF/S Ub ratio showed good discrimination between patients and controls: 22/29 (76%) of the AD patients and 9/14 (64%) of the VAD patients had a CSF/S Ub ratio that was higher than the highest control value. No significant differences in any of the parameters were found between AD and VAD. Ub is involved in an ATP-dependent proteolytic pathway and also acts as a heatshock protein. The increase in CSF-Ub in AD and VAD may therefore be interpreted as a cytoprotective response to abnormal or damaged proteins, and CSF-Ub may have a potential as a non-disease-specific marker for cerebral degeneration.


Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Demência Vascular/líquido cefalorraquidiano , Idoso , Doença de Alzheimer/diagnóstico , Biomarcadores/líquido cefalorraquidiano , Barreira Hematoencefálica/fisiologia , Demência Vascular/diagnóstico , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino
18.
Life Sci ; 55(25-26): 2125-34, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7997071

RESUMO

Gangliosides are glycosphingolipids localized to the outer leaflet of the plasma membrane of vertebrate cells. The highest ganglioside concentration of any organ is found in the mammalian brain, where the gangliosides are enriched in the neuronal membrane, particularly in the synapses. There are four major brain gangliosides with the same neutral tetrasaccharide core to which one to three sialic acids are linked--the simplest being the GM1-ganglioside. These gangliosides have been shown to have neuritogenic and neuronotrophic activity and to facilitate repair of neuronal tissue after mechanical, biochemical or toxic injuries. Mixtures of native bovine brain gangliosides were adopted for pharmacological use in the treatment of peripheral nerve damage, and GM1-ganglioside has been applied for the treatment of CNS injuries and diseases. Beneficial effects of GM1 have been documented in the treatment of stroke and spinal cord injuries, particularly when the treatment has been initiated within a few hours of the acute event. Continuous intraventricular infusion of GM1 has recently been shown to have a significant beneficial effect in Alzheimer disease of early onset (AD Type I).


Assuntos
Doença de Alzheimer/tratamento farmacológico , Transtornos Cerebrovasculares/tratamento farmacológico , Gangliosídeo G(M1)/uso terapêutico , Doença de Alzheimer/fisiopatologia , Animais , Sequência de Carboidratos , Transtornos Cerebrovasculares/fisiopatologia , Gangliosídeo G(M1)/farmacologia , Humanos , Dados de Sequência Molecular , Traumatismos da Medula Espinal/tratamento farmacológico
20.
Prog Brain Res ; 101: 213-23, 1994.
Artigo em Inglês | MEDLINE | ID: mdl-7518092

RESUMO

In this study, MAbs to the 'conventional' gangliosides expressed by human gliomas were generated and used to detect ganglioside species previously unisolated or defined in normal adult CNS tissue. Despite the marked phenotypic and genotypic heterogeneity shown by glioma cell lines (Bigner et al., 1981), the ganglioside phenotype of these cell lines is remarkably consistent qualitatively, if not quantitatively, in the ganglioside species expressed (Table V). The majority of cell lines and tumor samples express GM2, GD2 and GD3; this does not provide a diagnostic advantage (Vick et al., 1992). Nevertheless, as the relative amounts of these gangliosides in tumor as compared with normal adult CNS tissue is considerable, such reagents might be considered in compartmental immunotherapeutic approaches. Since GD2 and GD3 have been determined to mediate tumoricidal activity with human effector cells via specific antiganglioside epitope MAbs (Thurin et al., 1987; Kushner and Cheung, 1991; Barker et al., 1991; Reisfeld, 1993), cell-mediated approaches, as well as targeted immunoglobulin therapies, are also possible. The prospect of a more targeted approach with little or no effect on normal CNS tissue is now possible via the 'oncofetal' epitopes characteristic of 3'-isoLM1 and 3',6'-isoLD1. Several factors recommend the use of these moieties for compartmental immunotherapy; the inability to detect them within the adult CNS; the relatively high frequency of expression of 3'-isoLM1 and 3',6'-isoLD1, especially in human tumor samples (50-100%, depending upon the series and assay); and the existence of specific MAbs reactive with these epitopes. Current technology is being applied to these MAbs to transfer the specific recognition capacity of existing murine MAbs into various human framework structures of any desired immunoglobulin class, and thereby, biologic function. The variety of effector functions, the stability in affinity, labeling capacity, and the exquisite sensitivity of these MAbs for these glioma-distinctive epitopes is an exciting and promising approach for immunotherapy of human CNS tumors.


Assuntos
Neoplasias do Sistema Nervoso Central/química , Gangliosídeos/análise , Glioma/química , Anticorpos Monoclonais , Epitopos , Humanos
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