RESUMEN
BACKGROUND: The following study presents in detail newly occurring changes in driving ability of patients with Alzheimer's disease (AD) and dementia due to frontotemporal lobar degeneration (FTLD). PATIENTS AND METHODS: The caregivers of 30 patients with FTLD (20 with FTD, 10 with SD) and 26 matched patients with AD were interviewed on potential alterations in driving ability using a standardized questionnaire. RESULTS: Of the patients 90% with FTLD and 58% with AD showed changes in driving behavior. In AD the predominating alteration was an unsteady style of driving with increased lack of orientation. Patients with FTLD presented an aggressive and risky style of driving including various traffic rule violations. Significant differences between the two groups were observed regarding speeding, disregarding red traffic lights, inappropriate behavior and driving despite being forbidden by the family Of the patients with FTLD 37% were responsible for at least one accident since disease onset in comparison to 19% of patients with AD (p=0.24). Most patients with AD showed a reasonable attitude to their change in driving behavior, however the majority of patients with FTLD showed a lack of understanding for the fact that their style of driving presented a potential risk and did not accept the need to stop driving (p=0.023). CONCLUSION: Patients with FTLD should cease driving as soon as possible in the course of the disease. With patients suffering from mild AD an individual assessment should be made.
Asunto(s)
Accidentes de Tránsito/prevención & control , Accidentes de Tránsito/estadística & datos numéricos , Enfermedad de Alzheimer/epidemiología , Conducción de Automóvil/estadística & datos numéricos , Degeneración Lobar Frontotemporal/epidemiología , Análisis y Desempeño de Tareas , Anciano , Comorbilidad , Femenino , Alemania , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The nature and prevalence of misdemeanor in patients with dementia due to frontotemporal lobar degeneration has been described in a few case reports and in two small U.S. studies. Our clinical impression suggests that antisocial and aggressive behaviour are relatively frequent in this patient population. The objective of the present study was to verify this observation. For this purpose we developed a standardized questionnaire on misdemeanor in Frontotemporal Dementia. Using this instrument caregivers of 30 patients with Frontotemporal Dementia (FTD), 11 patients with Semantic dementia (SD) and 33 patients with Alzheimer-type dementia (AD) were interviewed. The interview included questions about theft, burglary, damaging other peoples' belongings, verbal or physical offence, bodily harm, drug abuse and use of weapons. Questions about the frequency of criminal behaviour, the amount of damages and consequences if applicable completed the questionnaire. Misdemeanor was found in half of the patients with FTD (15 out of 30) and in 7 out of 11 patients with SD, but only in one out of 33 patients with AD. The most frequent type of inappropriate behaviour was theft (13 patients), particularly shoplifting. 8 patients with FTD, 1 patient with SD and 1 patient with AD entered someone else's house without permission. 10 patients with FTD and 3 patients with SD but none of the patients with AD had physically threatened spouses, relatives or strangers. In one case another person was hurt.
Asunto(s)
Crimen/psicología , Demencia/psicología , Adulto , Anciano , Agresión/fisiología , Enfermedad de Alzheimer/psicología , Femenino , Humanos , Entrevista Psicológica , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Policia , Escalas de Valoración Psiquiátrica , Trastornos Relacionados con Sustancias/complicaciones , Trastornos Relacionados con Sustancias/psicologíaRESUMEN
CERAD-NAB (Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery) data were compared between 51 patients with frontotemporal dementia, 13 with semantic dementia, and 69 with Alzheimer's disease. There were statistically significant differences between the 3 groups. Compared with patients with Alzheimer's disease, patients with frontotemporal dementia were more impaired on Animal Fluency but not on any other CERAD-NAB subtest. Patients with semantic dementia performed worse in Animal Fluency and Boston Naming Test compared with frontotemporal dementia and Alzheimer's disease. Multiple logistic regression analysis revealed that in the differentiation between frontotemporal dementia and Alzheimer's disease, the combination of Animal Fluency and Boston Naming Test correctly classified 90.5% of patients. In segregating semantic dementia and Alzheimer's disease, the combination of Boston Naming Test and Mini Mental State Examination resulted in a correct classification of 96.3%. These findings demonstrate that the Mini Mental State Examination and the language subtests of the CERAD-NAB are valuable clinical instruments for the differential diagnosis between early frontotemporal dementia, semantic dementia, and Alzheimer's disease.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Demencia/diagnóstico , Escala del Estado Mental , Anciano , Enfermedad de Alzheimer/psicología , Demencia/psicología , Diagnóstico Diferencial , Femenino , Humanos , Lenguaje , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Semántica , Índice de Severidad de la EnfermedadRESUMEN
Antibodies may be viewed as adaptor molecules that provide a link between humoral and cellular defence mechanisms. Thus, when antigen-specific IgG antibodies form antigen/antibody immune complexes the effectively aggregated IgG can activate a wide range of effector systems. Multiple effector mechanisms result from cellular activation mediated through a family of IgG-Fc receptors differentially expressed on leucocytes. It is established that glycosylation of IgG-Fc is essential for recognition and activation of these ligands. IgG antibodies predominate in human serum and most therapeutic antibodies are of the IgG class. The IgG-Fc is a homodimer of N-linked glycopeptide chains comprised of two immunoglobulin domains (Cgamma2, Cgamma3) that dimerise via inter-heavy chain disulphide bridges at the N-terminal region and non-covalent interactions between the C-terminal Cgamma3 domains. The overall shape of the IgG-Fc is similar to that of a "horseshoe" with a majority of the internal space filled by the oligosaccharide chains, only attached through asparagine residues 297.To investigate the influence of individual sugar (monosaccharide) residues of the oligosaccharide on the structure and function of IgG-Fc we have compared the structure of "wild-type" glycosylated IgG1-Fc with that of four glycoforms bearing consecutively truncated oligosaccharides. Removal of terminal N-acetylglucosamine as well as mannose sugar residues resulted in the largest conformational changes in both the oligosaccharide and in the polypeptide loop containing the N-glycosylation site. The observed conformational changes in the Cgamma2 domain affect the interface between IgG-Fc fragments and FcgammaRs. Furthermore, we observed that the removal of sugar residues permits the mutual approach of Cgamma2 domains resulting in the generation of a "closed" conformation; in contrast to the "open" conformation which was observed for the fully galactosylated IgG-Fc, which may be optimal for FcgammaR binding. These data provide a structural rationale for the previously observed modulation of effector activities reported for this series of proteins.
Asunto(s)
Glicoproteínas/química , Glicoproteínas/inmunología , Fragmentos Fc de Inmunoglobulinas/química , Inmunoglobulina G/química , Isotipos de Inmunoglobulinas/química , Oligosacáridos/metabolismo , Cristalización , Glicoproteínas/metabolismo , Glicosilación , Humanos , Fragmentos Fc de Inmunoglobulinas/inmunología , Inmunoglobulina G/inmunología , Isotipos de Inmunoglobulinas/metabolismo , Mieloma Múltiple/inmunología , Mieloma Múltiple/patología , Oligosacáridos/inmunología , Unión Proteica , Conformación Proteica , Difracción de Rayos XRESUMEN
Caspases form a family of proteinases required for the initiation and execution phases of apoptosis. Distinct proapoptotic stimuli lead to activation of the initiator caspases-8 and -9, which in turn activate the common executioner caspases-3 and -7 by proteolytic cleavage. Whereas crystal structures of several active caspases have been reported, no three-dimensional structure of an uncleaved caspase zymogen is available so far. We have determined the 2.9-A crystal structure of recombinant human C285A procaspase-7 and have elucidated the activation mechanism of caspases. The overall fold of the homodimeric procaspase-7 resembles that of the active tetrameric caspase-7. Each monomer is organized in two structured subdomains connected by partially flexible linkers, which asymmetrically occupy and block the central cavity, a typical feature of active caspases. This blockage is incompatible with a functional substrate binding site/active site. After proteolytic cleavage within the flexible linkers, the newly formed chain termini leave the cavity and fold outward to form stable structures. These conformational changes are associated with the formation of an intact active-site cleft. Therefore, this mechanism represents a formerly unknown type of proteinase zymogen activation.
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Caspasas/metabolismo , Precursores Enzimáticos/metabolismo , Secuencia de Aminoácidos , Caspasa 7 , Caspasas/química , Cristalización , Dimerización , Electroforesis en Gel de Poliacrilamida , Activación Enzimática , Precursores Enzimáticos/química , Humanos , Hidrólisis , Modelos Moleculares , Datos de Secuencia Molecular , Conformación Proteica , Homología de Secuencia de Aminoácido , Especificidad por SustratoRESUMEN
RNA polymerase II subunit RPB8 is an essential subunit that is highly conserved throughout eukaryotic evolution and is present in all three types of nuclear RNA polymerases. We report the first high resolution structural insight into eukaryotic RNA polymerase architecture with the solution structure of RPB8 from Saccharomyces cerevisiae. It consists of an eight stranded, antiparallel beta-barrel, four short helical regions and a large, unstructured omega-loop. The strands are connected in classic Greek-key fashion. The overall topology is unusual and contains a striking C2 rotational symmetry. Furthermore, it is most likely a novel associate of the oligonucleotide/oligosaccharide (OB) binding protein class.