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1.
J Affect Disord ; 295: 781-787, 2021 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-34517252

RESUMEN

BACKGROUND: Borderline Personality Disorder (BPD) is a severe and disabling psychiatric syndrome, frequently associated with self-injurious behaviours (SIB). In recent years, functional magnetic resonance imaging (fMRI) investigations have tried to identify alterations associated with SIB amongst BPD patients, in order to better delineate possible neurobiological underpinnings of these manifestations. In this mini-review, we aimed at summarizing fMRI studies exploring patterns of neural activation associated with SIB in BPD patients. METHODS: Literature searches on PubMed, Psych-Info and Embase databases were performed for all fMRI studies including adult patients with BPD and SIB undergoing different tasks, including painful or thermic stimulation, affective stimulation through the presentation of picturesor the recollection of personal memories as well as tasks that evaluate sustained attention and impulsivity, and reward processing. Thirteen relevant papers were considered eligible for the present review. RESULTS: Patients with BPD and SIB, compared to HC, showed prefrontal, nucleus accumbens overactivation and amygdala deactivation during pain stimulation. During negative affective stimulation, BPD patients showed a hyperactivation of the amygdala and a hypoactivation of the orbitofrontal cortex (OFC), which was also found to be enhanced during a gambling task and during a recalling of aversive memories. In contrast, during cognitive tasks with negative affective interference, BPD patients showed hypoactivation of OFC, anterior cingulated cortex, and basal ganglia. LIMITATIONS: The limited number of studies and the heterogeneity regarding the fMRI tasks employed allowed only suggestive conclusions. CONCLUSIONS: The reviewed fMRI studies highlighted that BPD patients with a history of SIB showed altered brain activity, compared to HC, in regions involved in inhibitory cognitive processes and affect regulation, which may in turn, explain the overwhelming emotional experiences eliciting SIB in these patients.


Asunto(s)
Trastorno de Personalidad Limítrofe , Conducta Autodestructiva , Adulto , Amígdala del Cerebelo , Trastorno de Personalidad Limítrofe/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Emociones , Humanos , Imagen por Resonancia Magnética , Conducta Autodestructiva/diagnóstico por imagen
2.
Eur J Neurol ; 28(1): 56-65, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32896064

RESUMEN

BACKGROUND AND PURPOSE: CLOCK and PER2 genes have been implicated in sleep-wake cycle alterations and neurodegenerative diseases. Our aim was to evaluate the effect of CLOCK T3111C and PER2 C111G on cognitive functioning in subjective cognitive decline (SCD) patients and mild cognitive impairment (MCI) patients at the baseline of a longitudinal study, and the effect of these two polymorphisms on the progression to Alzheimer's disease (AD) of the two groups. METHODS: Sixty-eight subjects (41 SCD and 27 MCI) who underwent clinical evaluation, neuropsychological assessment, CLOCK and PER2 genotyping at baseline and neuropsychological follow-up every 2 years for a mean time of 10 years were included. Subjects who developed AD (SCD-c and MCI-c) and non-converters (SCD-nc, MCI-nc) were considered. RESULTS: CLOCK T3111C was detected in 47% of cases (21 SCD, 11 MCI) and PER2 C111G in 19% of cases (eight SCD and five MCI). PER2 G carriers presented lower premorbid intelligence score (P = 0.049), fewer years of education (P = 0.007) and a lower frequency of family history of AD (P = 0.04) than G non-carriers. MCI PER2 G carriers had worse performance in tests assessing memory, executive function, language and visuospatial abilities at baseline. During follow-up, two SCD and 15 MCI subjects progressed to AD: both of the SCD-c subjects presented the PER2 G allele, while none of the SCD PER2 G non-carriers converted to AD (P = 0.003). CONCLUSION: PER2 seems to have a role in cognitive reserve and cognition in SCD and MCI patients. Nevertheless, further studies are needed to assess the role of PER2 C111G on the risk of progression to AD.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Reserva Cognitiva , Enfermedad de Alzheimer/genética , Cognición , Disfunción Cognitiva/genética , Progresión de la Enfermedad , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Pruebas Neuropsicológicas , Proteínas Circadianas Period/genética
3.
Eur J Neurol ; 27(5): 894-899, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32043740

RESUMEN

BACKGROUND AND PURPOSE: Subjective cognitive decline (SCD) is a self-experienced decline in cognitive capacity with normal performance on standardized cognitive tests and has been shown to increase the risk of Alzheimer's disease (AD). SCD could also be related to other conditions such as normal aging, psychiatric, neurological or medical disorders. The SCD Initiative proposed a set of features (SCD-plus) that increase the likelihood of preclinical AD in individuals with SCD. Our aim was to assess the effect of these features on the risk of conversion from SCD to AD. METHODS: In total 150 SCD subjects who underwent extensive neuropsychological investigation, assessment of cognitive complaints and apolipoprotein E (ApoE) genotyping at baseline and clinical-neuropsychological follow-up for a mean time of 11 years were included. RESULTS: During the follow-up, 20 subjects developed AD. Considering SCD-plus features, age at onset ≥60 years and ApoE ε4 significantly increased the risk of conversion from SCD to AD. When our sample was stratified into three groups (no risk factor, one risk factor, two risk factors), the proportion of conversion was statistically significantly different between the three groups. CONCLUSIONS: Our model allows the risk of AD to be stratified in patients experiencing SCD according to age at onset and ApoE genotype.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/genética , Apolipoproteína E4/genética , Disfunción Cognitiva/diagnóstico , Progresión de la Enfermedad , Estudios de Seguimiento , Humanos , Pruebas Neuropsicológicas
4.
Protein Expr Purif ; 158: 44-50, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30772376

RESUMEN

Expression of recombinant proteins with baculovirus-infected insect larvae is a scarcely investigated alternative in comparison to that in insect cell lines, a system with growing popularity in the field of biotechnology. The aim of this study was to investigate the chromatographic behavior and physicochemical properties of the proteome of Rachiplusia nu larvae infected with recombinant Autographa californica multiple nucleopolyhedrosis virus (AcMNPV), in order to design rational purification strategies for the expression of heterologous proteins in this very complex and little-known system, based on the differential absorption between target recombinant proteins and the system's contaminating ones. Two-dimensional (2D) gel electrophoresis showed differences in the protein patterns of infected and non-infected larvae. Hydrophobic interaction matrices adsorbed the bulk of larval proteins, thus suggesting that such matrices are inappropriate for this system. Only 0.03% and 2.9% of the total soluble protein from the infected larval extract was adsorbed to CM-Sepharose and SP-Sepharose matrices, respectively. Immobilized metal ion affinity chromatography represented a solid alternative because it bound only 1.4% of the total protein, but would increase the cost of the purification process. We concluded that cation-exchange chromatography is the best choice for easy purification of high-isoelectric-point proteins and proteins with arginine tags, since very few contaminating proteins co-eluted with our target protein.


Asunto(s)
Histidina , Mariposas Nocturnas , Nucleopoliedrovirus , Proteínas Recombinantes de Fusión , Animales , Cromatografía Liquida , Histidina/biosíntesis , Histidina/química , Histidina/aislamiento & purificación , Histidina/farmacología , Larva/química , Larva/genética , Larva/metabolismo , Larva/virología , Mariposas Nocturnas/química , Mariposas Nocturnas/genética , Mariposas Nocturnas/metabolismo , Mariposas Nocturnas/virología , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/aislamiento & purificación
5.
AJNR Am J Neuroradiol ; 34(11): 2098-104, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23744687

RESUMEN

BACKGROUND AND PURPOSE: Manually drawn VOI-based analysis shows a decrease in magnetization transfer ratio in the hippocampus of patients with Alzheimer disease. We investigated with whole-brain voxelwise analysis the regional changes of the magnetization transfer ratio in patients with mild Alzheimer disease and patients with amnestic mild cognitive impairment. MATERIALS AND METHODS: Twenty patients with mild Alzheimer disease, 27 patients with amnestic mild cognitive impairment, and 30 healthy elderly control subjects were examined with high-resolution T1WI and 3-mm-thick magnetization transfer images. Whole-brain voxelwise analysis of magnetization transfer ratio maps was performed by use of Statistical Parametric Mapping 8 software and was supplemented by the analysis of the magnetization transfer ratio in FreeSurfer parcellation-derived VOIs. RESULTS: Voxelwise analysis showed 2 clusters of significantly decreased magnetization transfer ratio in the left hippocampus and amygdala and in the left posterior mesial temporal cortex (fusiform gyrus) of patients with Alzheimer disease as compared with control subjects but no difference between patients with amnestic mild cognitive impairment and either patients with Alzheimer disease or control subjects. VOI analysis showed that the magnetization transfer ratio in the hippocampus and amygdala was significantly lower (bilaterally) in patients with Alzheimer disease when compared with control subjects (ANOVA with Bonferroni correction, at P < .05). Mean magnetization transfer ratio values in the hippocampus and amygdala in patients with amnestic mild cognitive impairment were between those of healthy control subjects and those of patients with mild Alzheimer disease. Support vector machine-based classification demonstrated improved classification performance after inclusion of magnetization transfer ratio-related features, especially between patients with Alzheimer disease versus healthy subjects. CONCLUSIONS: Bilateral but asymmetric decrease of magnetization transfer ratio reflecting microstructural changes of the residual GM is present not only in the hippocampus but also in the amygdala in patients with mild Alzheimer disease.


Asunto(s)
Enfermedad de Alzheimer/patología , Amnesia/patología , Amígdala del Cerebelo/patología , Hipocampo/patología , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/complicaciones , Amnesia/complicaciones , Disfunción Cognitiva/complicaciones , Femenino , Humanos , Campos Magnéticos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
6.
Neurology ; 72(10): 928-34, 2009 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-19273828

RESUMEN

BACKGROUND: In amnestic mild cognitive impairment (aMCI), functional neuronal connectivity may be altered, as suggested by quantitative EEG and neuroimaging data. In young healthy humans, the execution of linguistic tasks modifies the excitability of the hand area of the dominant primary motor cortex (M1(hand)), as tested by transcranial magnetic stimulation (TMS). We used TMS to investigate functional connectivity between language-related cortical areas and M1(hand) in aMCI. METHODS: Ten elderly women with aMCI and 10 age-matched women were recruited. All participants were right handed and underwent a neuropsychological evaluation. In the first TMS experiment, participants performed three different tasks: reading aloud, viewing of non-letter strings (baseline), and nonverbal oral movements. The second experiment included the baseline condition and three visual searching/matching tasks using letters, geometric shapes, or digits as target stimuli. RESULTS: In controls, motor evoked potentials (MEP) elicited by suprathreshold TMS of the left M1(hand) were significantly larger during reading aloud (170% baseline) than during nonverbal oral movements, whereas no difference was seen for right M1(hand) stimulation. Similarly, MEP elicited by left M1(hand) stimulation during letter and shape searching/matching tasks were significantly larger compared to digit task. In contrast, linguistic task performance did not produce any significant MEP modulation in patients with aMCI, although neuropsychological evaluation showed normal language abilities. CONCLUSIONS: Findings suggest that functional connectivity between the language-related brain regions and the dominant M1(hand) may be altered in amnestic mild cognitive impairment. Follow-up studies will reveal whether transcranial magnetic stimulation application during linguistic tasks may contribute to characterize the risk of conversion to Alzheimer disease.


Asunto(s)
Corteza Cerebral/fisiología , Trastornos del Conocimiento/fisiopatología , Trastornos del Conocimiento/psicología , Corteza Motora/fisiología , Desempeño Psicomotor/fisiología , Lectura , Anciano , Cognición/fisiología , Interpretación Estadística de Datos , Electroencefalografía , Potenciales Evocados Motores/fisiología , Femenino , Percepción de Forma/fisiología , Humanos , Lenguaje , Movimiento/fisiología , Pruebas Neuropsicológicas , Estimulación Luminosa , Estimulación Magnética Transcraneal
7.
J Neurol ; 256(6): 925-32, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19252791

RESUMEN

Presenilin 1 (PS1) mutation carriers provide the opportunity to asses early features of neurodegeneration in familial Alzheimer's disease (AD). Gray matter (GM) regional volume loss and decrease of magnetization transfer ratio (MTR) consistent with microstructural changes have been reported in sporadic AD. We performed a regional volumetric and MTR analysis in carriers of PS1 mutations. Six non-demented mutated PS1 carriers (5 with memory deficits) and 14 healthy subjects were examined with high resolution T1-weighted images for volumetry and with T2* weighted images for MTR. Cortical GM volume and MTR values were derived. Compared to healthy controls, the GM volume of the left temporal and inferior parietal cortex and the MTR of the temporal cortex bilaterally were significantly decreased in PS1 gene carriers. In the latter, the temporal lobe MTR showed a trend for correlation with memory and executive function scores. Early neurodegeneration in non-demented subjects at risk for familial AD may be associated with atrophy and decreased MTR in the temporal cortex.


Asunto(s)
Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Encéfalo/patología , Presenilina-1/genética , Adulto , Análisis de Varianza , Familia , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Mutación , Pruebas Neuropsicológicas , Tamaño de los Órganos , Lóbulo Parietal/patología , Factores de Riesgo , Lóbulo Temporal/patología
8.
J Phys Chem B ; 112(37): 11506-16, 2008 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-18712906

RESUMEN

Polymers with general formula ([(vpy) 2vpyRe(CO) 3(tmphen) (+)]) n ([(vpy) 2vpyRe(CO) 3(NO 2-phen) (+)]) m (NO 2-phen = 5-nitro-1,10-phenanthroline; tmphen = 3,4,7,8-tetramethyl-1,10-phenanthroline); vpy = 4-vinylpyridine) were prepared and their morphologies were studied by transmission electron microscopy (TEM). Multiple morphologies of aggregates from these Re I polymers were obtained by using different solvents. Energy transfer between MLCT Re-->tmphen and MLCT Re-->NO 2 -phen excited states inside the polymers was evidenced by steady state and time-resolved spectroscopy. Current Forster resonance energy transfer theory was successfully applied to energy transfer processes in these polymers.

9.
J Neurol ; 254(8): 1052-65, 2007 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17385079

RESUMEN

This study was designed to examine the correlations between resting-state brain glucose metabolism (CMRglc), as measured with Positron Emission Tomography and performance on executive function tasks in Alzheimer's disease (AD), while taking into account the severity of cognitive deterioration. We addressed this issue in 50 AD patients, classified as very mild (n = 22) and mild (n = 28) AD on the basis of an extensive neuropsychological battery. Thirteen healthy subjects were selected as controls for the neuropsychological measures. Statistical Parametric Mapping (SPM) was used to examine voxel-wise correlations between CMRglc and scores on selected cognitive tests of executive functions: the Stroop Test, the Trail Making Test, the Dual Task and the Phonemic Fluency, while correcting for age and global CMRglc. All analyses were done separately for the two AD subgroups. The very mild AD patients showed significant associations between Stroop and Trail Making Test scores and prefrontal regions metabolism, whereas the mild AD patients exhibited more widely distributed cognitive-metabolic correlations extending to the posterior brain regions. These data suggest that a large cortical network is implicated in executive dysfunction in AD, and that the pattern of cognitive-metabolic correlations varies according to disease severity.


Asunto(s)
Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/metabolismo , Trastornos del Conocimiento/etiología , Glucosa/metabolismo , Solución de Problemas/fisiología , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico por imagen , Análisis de Varianza , Mapeo Encefálico , Trastornos del Conocimiento/diagnóstico por imagen , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Pruebas Neuropsicológicas , Tomografía de Emisión de Positrones/métodos , Estadística como Asunto
10.
Oncogene ; 25(12): 1821-31, 2006 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-16261155

RESUMEN

Head and neck squamous cell carcinoma (HNSCC) is common worldwide and is associated with a poor rate of survival. Identification of new markers and therapeutic targets, and understanding the complex transformation process, will require a comprehensive description of genome expression, that can only be achieved by combining different methodologies. We report here the HNSCC transcriptome that was determined by exhaustive differential display (DD) analysis coupled with validation by different methods on the same patient samples. The resulting 820 nonredundant sequences were analysed by high throughput bioinformatics analysis. Human proteins were identified for 73% (596) of the DD sequences. A large proportion (>50%) of the remaining unassigned sequences match ESTs (expressed sequence tags) from human tumours. For the functionally annotated proteins, there is significant enrichment for relevant biological processes, including cell motility, protein biosynthesis, stress and immune responses, cell death, cell cycle, cell proliferation and/or maintenance and transport. Three of the novel proteins (TMEM16A, PHLDB2 and ARHGAP21) were analysed further to show that they have the potential to be developed as therapeutic targets.


Asunto(s)
Carcinoma de Células Escamosas/genética , ADN de Neoplasias/análisis , Perfilación de la Expresión Génica/métodos , Neoplasias de Cabeza y Cuello/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Análisis por Matrices de Proteínas , Secuencia de Aminoácidos , Secuencia de Bases , Northern Blotting , Biología Computacional , Expresión Génica , Genómica , Humanos , Inmunohistoquímica , Datos de Secuencia Molecular , Proteoma , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADN/métodos
11.
Dement Geriatr Cogn Disord ; 20(6): 358-66, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16192726

RESUMEN

This study investigated the contribution that white matter changes (WMCs) make to clinical and cognitive features in Alzheimer's disease (AD), independently of possible confounders such as cortical atrophy and the apolipoprotein E genotype as well as their relationship to vascular risk factors. We semiquantitatively assessed the degree and location of WMCs (global, periventricular and deep white matter), lacunes and global atrophy on brain MRI scans of 86 AD cases, extensively evaluated from a clinical and neuropsychological point of view. Multivariate logistic and linear regression analysis showed that age was the only significant predictor of all WMC measures and revealed a significant association of periventricular WMCs with performance on executive function tasks as well as of deep WMCs with history of mood depression. Our results underline the significance of WMC location over size in the occurrence of specific cognitive deficits in AD.


Asunto(s)
Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/psicología , Encéfalo/patología , Trastornos del Conocimiento/patología , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Apolipoproteínas E/análisis , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas
12.
Neurol Sci ; 26(2): 61-6, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15995821

RESUMEN

Cognitive impairment and gait disturbances are the most frequent clinical findings in patients with leukoaraiosis (LA). Corpus callosum (CC) atrophy has been associated with dementia in patients with LA, as well as with gait disturbances in patients with normal pressure hydrocephalus. We investigated, in patients with LA, the possible association between gait impairment and CC atrophy, taking into account cognitive deficits and the other brain lesions commonly present in these patients. Thirty patients (M:F=21:9; mean age 72.5+/-6.3 years) with gait disturbances and brain CT images consistent with LA underwent an assessment of gait and a cognitive assessment of global and selective functions. Magnetic resonance imaging (MRI) was used to measure thickness and area of the CC, total LA volume, lacunar infarcts and size of lateral ventricles. We examined the effect of every MRI change on each performance measure. Reduction of CC thickness, particularly that of the anterior segment, had a significant effect on severity of gait impairment, as measured using the gait scale's score. It was independent of any other brain changes revealed by MRI, including LA. An independent, significant association was also found between CC area and the Left Hand Praxis test results. In patients with LA, CC atrophy is associated with gait impairment independently of LA and other brain abnormalities usually present in these patients.


Asunto(s)
Cuerpo Calloso/patología , Trastornos Neurológicos de la Marcha/patología , Leucoaraiosis/patología , Anciano , Atrofia , Trastornos del Conocimiento/patología , Trastornos del Conocimiento/fisiopatología , Femenino , Trastornos Neurológicos de la Marcha/complicaciones , Humanos , Leucoaraiosis/complicaciones , Imagen por Resonancia Magnética/métodos , Masculino , Escala del Estado Mental , Persona de Mediana Edad , Análisis de Regresión , Tomografía Computarizada por Rayos X/métodos
13.
J Neurol Neurosurg Psychiatry ; 76(1): 15-23, 2005 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15607989

RESUMEN

BACKGROUND: Clinically apparent Alzheimer's disease (AD) is thought to result when brain tissue damage exceeds a critical threshold of "brain reserve", a process possibly accelerated by the apolipoprotein E (ApoE) E4 allele. The interaction between onset age and ApoE genotype was investigated to assess whether early disease onset (<65 years) in patients carrying the E4 allele is associated with greater cerebral metabolic (regional cerebral metabolic rate of glucose utilisation, rCMRgl) reduction. METHODS: AD patients, divided into early (EOAD; 27 patients) and late onset (LOAD; 65 patients) groups, both groups balanced as to the number of E4 carriers (E4+) and non-carriers (E4-), and matched controls (NC; 35 cases) underwent (18)F-FDG PET ([(18)F]fluorodeoxyglucose positron emission tomography) scanning. SPM'99 software was used to compare AD patients to NC and to perform a two way ANOVA with onset age and ApoE genotype as grouping factors. Results were considered significant at p<0.001, uncorrected. RESULTS: AD patients demonstrated rCMRgl reductions compared to NC, with rCMRgl lower in association cortex and relatively higher in limbic areas in EOAD compared to LOAD subjects. rCMRgl was lower in the anterior cingulate and frontal cortex for E4+ compared to E4- subjects. A significant onset age by ApoE interaction was detected in the hippocampi and basal frontal cortex, with EOAD E4+ subjects having the greatest rCMRgl reduction. CONCLUSIONS: The interactive effects of early onset age, possibly reflecting lower brain reserve, and ApoE E4 allele, possibly leading to greater tissue damage, lead to reduced tolerance to the pathophysiological effects of AD in key brain regions.


Asunto(s)
Edad de Inicio , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Apolipoproteínas E/genética , Encéfalo/metabolismo , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Estudios de Casos y Controles , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Radiofármacos/farmacocinética
14.
Neurology ; 63(12): 2332-40, 2004 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-15623696

RESUMEN

OBJECTIVES: To investigate whether the combination of fluoro-2-deoxy-d-glucose (FDG) PET measures with the APOE genotype would improve prediction of the conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD). METHOD: After 1 year, 8 of 37 patients with MCI converted to AD (22%). Differences in baseline regional glucose metabolic rate (rCMRglc) across groups were assessed on a voxel-based basis using a two-factor analysis of variance with outcome (converters [n = 8] vs nonconverters [n = 29]) and APOE genotype (E4 carriers [E4+] [n = 16] vs noncarriers [E4-] [n = 21]) as grouping factors. Results were considered significant at p < 0.05, corrected for multiple comparisons. RESULTS: All converters showed reduced rCMRglc in the inferior parietal cortex (IPC) as compared with the nonconverters. Hypometabolism in AD-typical regions, that is, temporoparietal and posterior cingulate cortex, was found for the E4+ as compared with the E4- patients, with the E4+/converters (n = 5) having additional rCMRglc reductions within frontal areas, such as the anterior cingulate (ACC) and inferior frontal (IFC) cortex. For the whole MCI sample, IPC rCMRglc predicted conversion to AD with 84% overall diagnostic accuracy (p = 0.003). Moreover, ACC and IFC rCMRglc improved prediction for the E4+ group, yielding 100% sensitivity, 90% specificity, and 94% accuracy (p < 0.0005), thus leading to an excellent discrimination. CONCLUSION: Fluoro-2-deoxy-d-glucose-PET measures may improve prediction of the conversion to Alzheimer disease, especially in combination with the APOE genotype.


Asunto(s)
Enfermedad de Alzheimer/diagnóstico por imagen , Apolipoproteínas E/genética , Encéfalo/diagnóstico por imagen , Trastornos del Conocimiento/diagnóstico por imagen , Tomografía de Emisión de Positrones , Anciano , Alelos , Enfermedad de Alzheimer/genética , Apolipoproteína E4 , Encéfalo/metabolismo , Trastornos del Conocimiento/genética , Progresión de la Enfermedad , Metabolismo Energético , Femenino , Fluorodesoxiglucosa F18 , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Trastornos de la Memoria/diagnóstico por imagen , Trastornos de la Memoria/genética , Recuerdo Mental , Persona de Mediana Edad , Pruebas Neuropsicológicas , Valor Predictivo de las Pruebas , Radiofármacos , Método Simple Ciego
15.
Br J Cancer ; 91(2): 258-61, 2004 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-15213722

RESUMEN

We report that homeodomain-only protein (HOP) is expressed in the suprabasal layer of normal upper aerodigestive tract epithelium and expression strongly decreases in hypopharyngeal carcinoma. Interestingly, HOP has very recently been shown to be a tumour suppressor involved in differentiation, suggesting that HOP may have a similar role in head and neck squamous cell carcinoma (HNSSC).


Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Genes Supresores de Tumor , Neoplasias de Cabeza y Cuello/genética , Proteínas de Homeodominio/genética , Northern Blotting , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Diferenciación Celular , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Proteínas de Homeodominio/metabolismo , Humanos , Hibridación in Situ , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas Supresoras de Tumor
16.
J Neurol Neurosurg Psychiatry ; 75(3): 370-6, 2004 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-14966149

RESUMEN

OBJECTIVES: Declines in brain glucose metabolism have been described early in Alzheimer's disease (AD), and there is evidence that a genetic predisposition to AD contributes to accelerate this process. The epsilon 4 (e4) allele of the apolipoprotein E (ApoE) gene has been implicated as a major risk factor in this process. The aim of this FDG-PET study was to assess the ApoE e4 dose related effect on regional cerebral glucose metabolism (METglc) in clinical AD patients, with statistical voxel based methods. METHODS: Eighty six consecutive mild to moderate AD patients included in the Network for Efficiency and Standardisation of Dementia Diagnosis database underwent FDG-PET scans at rest. PCR was used to determine the ApoE genotype. Patients were grouped as e4 non-carriers (n = 46), e3/e4 (n = 27) and e4/e4 (n = 13) carriers. A voxel-based mapping program was used to compare each AD subgroup with a database of 35 sex and age matched controls (p<0.001, corrected for cluster extent) and also to compare between the subgroups (p<0.001, uncorrected). RESULTS: No difference was found as to age at examination, age at onset, sex, disease duration, educational level, or severity of dementia between AD subgroups. Compared with controls, all AD subgroups had equivalent METglc reductions in the precuneus, posterior cingulate, parietotemporal, and frontal regions. Direct comparisons between AD subgroups indicated that patients with at least one e4 allele had METglc reductions within additional associative and limbic areas compared with e4 non-carriers. CONCLUSIONS: The present FDG-PET study showed different metabolic phenotypes related to the ApoE genotype in clinical AD patients, as revealed with voxel based statistical methods. The results suggest a generalised disorder in e4 carriers impairing metabolism globally, in addition to the more localised changes typical of AD patients.


Asunto(s)
Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/fisiopatología , Apolipoproteínas E/genética , Encéfalo/metabolismo , Dosificación de Gen , Predisposición Genética a la Enfermedad , Glucosa/metabolismo , Anciano , Enfermedad de Alzheimer/diagnóstico por imagen , Apolipoproteína E4 , Estudios de Casos y Controles , Femenino , Fluorodesoxiglucosa F18 , Humanos , Masculino , Fenotipo , Radiofármacos , Índice de Severidad de la Enfermedad , Tomografía Computarizada de Emisión
17.
Br J Cancer ; 89(10): 1940-9, 2003 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-14612907

RESUMEN

Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer in men with an incidence of about 780000 new cases per year worldwide and a poor rate of survival. There is a need for a better understanding of HNSCC, for the development of rational targeted interventions and to define new prognostic or diagnostic markers. To address these needs, we performed a large-scale differential display comparison of hypopharyngeal HNSCCs against histologically normal tissue from the same patients. We have identified 70 genes that exhibit a striking difference in expression between tumours and normal tissues. There is only a limited overlap with other HNSCC gene expression studies that have used other techniques and more heterogeneous tumour samples. Our results provide new insights into the understanding of HNSCC. At the genome level, a series of differentially expressed genes cluster at 12p12-13 and 1q21, two hotspots of genome disruption. The known genes share functional relationships in keratinocyte differentiation, angiogenesis, immunology, detoxification, and cell surface receptors. Of particular interest are the 13 'unknown' genes that exist only in EST, theoretical cDNA and protein databases, or as chromosomal locations. The differentially expressed genes that we have identified are potential new markers and therapeutic targets.


Asunto(s)
Carcinoma de Células Escamosas/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/genética , Anciano , Northern Blotting , Carcinoma de Células Escamosas/patología , Diferenciación Celular , Cartilla de ADN , ADN Complementario , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Queratinocitos , Masculino , Persona de Mediana Edad , Neovascularización Patológica , Reacción en Cadena de la Polimerasa
18.
Neurology ; 61(8): 1138-40, 2003 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-14581683

RESUMEN

This FDG-PET study with SPM99 compared 46 patients with sporadic Alzheimer disease (SAD) to 40 patients with familial AD (FAD) and to 35 matched controls. AD groups had equivalent metabolic (METglu) reductions in several cortical and limbic areas with respect to the controls. Patients with FAD showed decreased METglu in the posterior cingulate, parahippocampal, and occipital cortex as compared to the patients with SAD (p < 0.001). Genetic factors lead to phenotypic differences in AD.


Asunto(s)
Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Glucosa/metabolismo , Edad de Inicio , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Femenino , Fluorodesoxiglucosa F18/farmacocinética , Pruebas Genéticas , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Fenotipo , Valores de Referencia , Tomografía Computarizada de Emisión
19.
J Neurol Sci ; 188(1-2): 85-93, 2001 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-11489290

RESUMEN

BACKGROUND AND PURPOSE: The majority of studies on neuropsychological complications after cardiac surgery used the raw variation of selective tests scores to define the occurrence of cognitive decline. We prospectively estimated the frequency of cognitive impairment after cardiac surgery, with a particular emphasis on persistent and clinically relevant cognitive decline. Possible baseline and operative predictors were also evaluated. METHODS: An extensive neuropsychological battery was administered to 110 patients (mean age 64.1+/-9.4 years; 70.9% males) undergoing cardiac surgery before and 6 months after the operation. After evaluating the variations in the cognitive performances, two independent neuropsychologists ranked the patients as unchanged-improved, mildly-moderately deteriorated, or severely deteriorated, using a global and functionally oriented judgement. The degree of the impairment was determined in relation to its impact on everyday life activities. RESULTS: Ten patients (9.1%) were ranked as severely deteriorated, 22 (20%) as mildly-moderately deteriorated, and 78 (70.9%) as unchanged-improved. Cognitively impaired patients were older (p=0.031), more often females (p=0.005), with a low education level (p=0.013). At multivariate analysis, female gender (odds ratio (OR) 6.14, 95% confidence interval (95% CI) 2.16-17.50), baseline use of beta-blockers (OR 4.55, 95% CI 1.30-15.92), and PaO2 at arrival in intensive care unit (OR for 1 mm Hg increment 1.012, 95% CI 1.004-1.020) were significant predictors of cognitive impairment of any degree. Positive predictors of severe cognitive impairment were history of hypertension (OR 5.33, 95% CI 1.03-27.64) and PaO2 at arrival intensive care unit (OR for 1 mm Hg increment 1.020, 95% CI 1.006-1.035), while education was protective (OR per year of increment 0.53, 95% CI 0.31-0.90). CONCLUSIONS: A considerable proportion of cardiac surgery patients may undergo clinically relevant cognitive impairment. The knowledge of variables influencing cognitive outcome is essential for the adoption of preventive measures.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos/efectos adversos , Trastornos del Conocimiento/etiología , Adulto , Anciano , Anciano de 80 o más Años , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/epidemiología , Trastornos del Conocimiento/psicología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pruebas Neuropsicológicas , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad
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