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2.
Neuron ; 22(3): 615-21, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10197540

RESUMO

Apart from being a common feature of mental illness, auditory hallucinations provide an intriguing model for the study of internally generated sensory perceptions that are attributed to external sources. Until now, the knowledge about the cortical network that supports such hallucinations has been restricted by methodological limitations. Here, we describe an experiment with paranoid schizophrenic patients whose on- and offset of auditory hallucinations could be monitored within one functional magnetic resonance imaging (fMRI) session. We demonstrate an increase of the blood oxygen level-dependent (BOLD) signal in Heschl's gyrus during the patients' hallucinations. Our results provide direct evidence of the involvement of primary auditory areas in auditory verbal hallucinations and establish novel constraints for psychopathological models.


Assuntos
Córtex Auditivo/fisiopatologia , Alucinações/fisiopatologia , Esquizofrenia Paranoide/fisiopatologia , Estimulação Acústica , Adulto , Córtex Auditivo/patologia , Mapeamento Encefálico , Feminino , Alucinações/patologia , Audição , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Oxigênio/sangue , Psicologia do Esquizofrênico
3.
Nat Genet ; 20(1): 51-3, 1998 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9731530

RESUMO

All molybdoenzymes other than nitrogenase require molybdopterin as a metal-binding cofactor. Several genes necessary for the synthesis of the molybdenum cofactor (MoCo) have been characterized in bacteria and plants. The proteins encoded by the Escherichia coli genes moaA and moaC catalyse the first steps in MoCo synthesis. The human homologues of these genes are therefore candidate genes for molybdenum cofactor deficiency, a rare and fatal disease. Using oligonucleotides complementary to a conserved region in the moaA gene, we have isolated a human cDNA derived from liver mRNA. This transcript contains an open reading frame (ORF) encoding the human moaA homologue and a second ORF encoding a human moaC homologue. Mutations can be found in the majority of MoCo-deficient patients that confirm the functional role of both ORFs in the corresponding gene MOCS1 (for 'molybdenum cofactor synthesis-step 1'). Northern-blot analysis detected only full-length transcripts containing both consecutive ORFs in various human tissues. The mRNA structure suggests a translation reinitiation mechanism for the second ORF. These data indicate the existence of a eukaryotic mRNA, which as a single and uniform transcript guides the synthesis of two different enzymatic polypeptides with disease-causing potential.


Assuntos
Coenzimas , Erros Inatos do Metabolismo/genética , Metaloproteínas/metabolismo , Mutação , Proteínas Nucleares/genética , Pteridinas/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Carbono-Carbono Liases , Sequência Conservada , Feminino , Humanos , Masculino , Dados de Sequência Molecular , Cofatores de Molibdênio , Proteínas Nucleares/metabolismo , Fases de Leitura Aberta , Linhagem , RNA Mensageiro , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos
4.
Phytomedicine ; 5(6): 417-24, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23196024

RESUMO

Among the psychiatric illnesses associated with old age primary degenerative dementia of the Alzheimer type (DAT) has gained increasing importance in recent years. Even though a curative treatment of the disease is currently impossible, various drugs can be used to slow down its progression. In the present study the influence of oral treatment with 240 mg/day of Ginkgo biloba special extract EGb 761 (Tebonin® forte, manufactured by Dr. Willmar Schwabe, Karlsruhe) on the clinical course of DAT was investigated in a double-blind, randomized, placebo-controlled parallel-group design in 20 outpatients. The duration of treatment was 3 months. The primary outcome variable was the sum score in the SKT-test for the determination of attention and memory. Other psychometric tests (trailmaking test, ADAS, CGI) and electrophysiological investigations (EEG topography) were evaluated descriptively. Although the active-treatment group, with a mean sum score of 19.67 points in the S.K.T., had a poorer baseline level than the placebo group (18.11 points), it experienced an improvement to 16.78 points under treatment with EGb 761 whereas the placebo group deteriorated to 18.89 points. The differences between the baseline and final values formed the basis for a statistical group comparison, which gave a result favourable to EGb 761, at a significance level of p <.013. In addition to this psychometric confirmation of efficacy, certain descriptive trends were found at the psychopathological (Clinical Global Impression) and dynamic functional (EEG findings) levels, which can be interpreted as evidence of effectiveness of Ginkgo biloba special extract EGb 761 in mild to moderate dementia and of local effects in the central nervous system. Inter-group differences in the ADAS cognitive and non-cognitive subscales did not reach statistical significance, probably because of the small sample size.

5.
J Psychiatr Res ; 31(6): 645-55, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9447569

RESUMO

Among the psychiatric illnesses associated with old age primary degenerative dementia of the Alzheimer type (DAT) has gained increasing importance in recent years. Even though a curative treatment of the disease is currently impossible, various drugs can be used to slow down its progression. In the present study the influence of oral treatment with 240 mg/day of Ginkgo bilabo special extract EGb 761 (Tebonin forte, manufactured by Dr Willmar Schwabe, Karlsruhe) on the clinical course of DAT was investigated in a double-blind, randomized, placebo-controlled parallel-group design in 20 outpatients. The duration of treatment was 3 months. The primary outcome variable was the sum score in the SKT-test for the determination of attention and memory. Other psychometric tests (trailmaking test, ADAS, CGI) and electrophysiological investigations (EEG topography) were evaluated descriptively. Although the active-treatment group, with a mean sum score of 19.67 points in the, S.K.T., had a poorer baseline level than the placebo group (18.11 points), it experienced an improvement to 16.78 points under treatment with EGb 761 whereas the placebo group deteriorated to 18.89 points. The differences between the baseline and final values formed the basis for a statistical group comparison, which gave a result favourable to EGb 761, at a significance level of p < .013. In addition to this psychometric confirmation of efficacy, certain descriptive trends were found at the psychopathological (Clinical Global Impression) and dynamic functional (EEG findings) levels, which can be interpreted as evidence of effectiveness of Ginkgo biloba special extract EGb 761 in mild to moderate dementia and of local effects in the central nervous system. Inter-group differences in the ADAS cognitive and non-cognitive subscales did not reach statistical significance, probably because of the small sample size.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Sequestradores de Radicais Livres/uso terapêutico , Extratos Vegetais/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Método Duplo-Cego , Feminino , Ginkgo biloba , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos
6.
EMBO J ; 15(24): 6931-42, 1996 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-9003769

RESUMO

Protein transport into the mammalian endoplasmic reticulum depends on nucleoside triphosphates. Photoaffinity labelling of microsomes with azido-ATP prevents protein transport at the level of association of precursor proteins with the components of the transport machinery, Sec61alpha and TRAM proteins. The same phenotype of inactivation was observed after depleting a microsomal detergent extract of ATP-binding proteins by passage through ATP-agarose and subsequent reconstitution of the pass-through into proteoliposomes. Transport was restored by co-reconstitution of the ATP eluate. This eluate showed eight distinct bands in SDS gels. We identified five lumenal proteins (Grp170, Grp94, BiP/Grp78, calreticulin and protein disulfide isomerase), one membrane protein (ribophorin I) and two ribosomal proteins (L4 and L5). In addition to BiP (Grp78), Grp170 was most efficiently retained on ATP-agarose. Purified BiP did not stimulate transport activity. Sequence analysis revealed a striking similarity of Grp170 and the yeast microsomal protein Lhs1p which was recently shown to be involved in protein transport into yeast microsomes. We suggest that Grp170 mediates efficient insertion of polypeptides into the microsomal membrane at the expense of nucleoside triphosphates.


Assuntos
Trifosfato de Adenosina/metabolismo , Proteínas de Transporte/metabolismo , Retículo Endoplasmático/metabolismo , Proteínas de Choque Térmico , Microssomos/metabolismo , Sequência de Aminoácidos , Animais , Transporte Biológico , Proteínas de Transporte/genética , Clonagem Molecular , DNA Complementar , Cães , Chaperona BiP do Retículo Endoplasmático , Chaperonas Moleculares/metabolismo , Dados de Sequência Molecular , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
7.
J Neural Transm (Vienna) ; 103(11): 1351-9, 1996.
Artigo em Inglês | MEDLINE | ID: mdl-9013421

RESUMO

Auditory P300-amplitudes have been found to be correlated with the social functioning and with the impairment in daily life by negative symptoms in cross-sectional studies. In this prospective longitudinal study, the correlation of auditory P300-amplitudes registrated at the index examination was investigated with the clinical outcome after an average of 2.4 years. Based on previous studies, only schizophrenic patients who were in a stabilized residual state were included in the study. Reference-independent P300-parameters of the index examination were correlated with axis V of DSM-III-R (GAF), with the Brief Psychiatric Rating Scale (BPRS) and with the Scale for Assessment of Negative Symptoms (SANS) assessed at the follow-up examination. The correlation of index P300-amplitude with social functioning at follow-up was significant. No correlations of index P300 with the current symptomatology at follow-up, as expressed by BPRS and SANS was found, however. The results indicate a predictive value of the P300-amplitude on the clinical outcome in terms of social functioning of schizophrenic patients.


Assuntos
Potenciais Evocados P300/fisiologia , Esquizofrenia/fisiopatologia , Estimulação Acústica , Adulto , Feminino , Seguimentos , Humanos , Masculino , Valor Preditivo dos Testes , Escalas de Graduação Psiquiátrica , Psicologia do Esquizofrênico
8.
Neuropsychobiology ; 27(1): 54-60, 1993.
Artigo em Inglês | MEDLINE | ID: mdl-8515825

RESUMO

The parameters of auditory P300 were studied with reference-independent methods in a group of 18 remitted and residual schizophrenics, and in 18 age- and sex-matched controls. In the schizophrenic group, significant inverse correlations were found between P300 amplitudes and level of psychopathology assessed with the Scale for Assessment of Negative Symptoms and with the Brief Psychiatric Rating Scale. Clinical variables regarding social functioning and adaptation, assessed with the Schedule for Affective Disorders and Schizophrenia, and with axis V of DSM-III-R, correlated significantly with low amplitudes. The scalp locations of the maxima and minima of the P300 potentials had the tendency to be dislocated to the right in schizophrenics compared with controls. The results indicate low P300 amplitudes to be associated with pervasive cognitive impairment. Future studies will determine whether low P300 amplitudes have prognostic validity for course and outcome of schizophrenic disorders.


Assuntos
Potenciais Evocados Auditivos , Esquizofrenia/fisiopatologia , Estimulação Acústica , Adulto , Idoso , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tempo de Reação/fisiologia
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