WILSON JACOB FILHO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/66, Hospital das Clínicas, Faculdade de Medicina - Líder
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/66, Hospital das Clínicas, Faculdade de Medicina - Líder
7 resultados
Resultados de Busca
Agora exibindo 1 - 7 de 7
- Repair of Oxidative DNA Damage, Cell-Cycle Regulation and Neuronal Death May Influence the Clinical Manifestation of Alzheimer's Disease(2014) SILVA, Aderbal R. T.; SANTOS, Ana Cecilia Feio; FARFEL, Jose M.; GRINBERG, Lea T.; FERRETTI, Renata E. L.; CAMPOS, Antonio Hugo Jose Froes Marques; CUNHA, Isabela Werneck; BEGNAMI, Maria Dirlei; ROCHA, Rafael M.; CARRARO, Dirce M.; PEREIRA, Carlos Alberto de Braganca; JACOB-FILHO, Wilson; BRENTANI, HelenaAlzheimer's disease (AD) is characterized by progressive cognitive decline associated with a featured neuropathology (neuritic plaques and neurofibrillary tangles). Several studies have implicated oxidative damage to DNA, DNA repair, and altered cell-cycle regulation in addition to cell death in AD post-mitotic neurons. However, there is a lack of studies that systematically assess those biological processes in patients with AD neuropathology but with no evidence of cognitive impairment. We evaluated markers of oxidative DNA damage (8-OHdG, H2AX), DNA repair (p53, BRCA1, PTEN), and cell-cycle (Cdk1, Cdk4, Cdk5, Cyclin B1, Cyclin D1, p(27Kip1), phospho-Rb and E2F1) through immunohistochemistry and cell death through TUNEL in autopsy hippocampal tissue samples arrayed in a tissue microarray (TMA) composed of three groups: I) ""clinical-pathological AD"" (CP-AD) - subjects with neuropathological AD (Braak >= IV and CERAD = B or C) and clinical dementia (CDR >= 2, IQCODE >= 3.8); II) ""pathological AD"" (P-AD) - subjects with neuropathological AD (Braak >= IV and CERAD = B or C) and without cognitive impairment (CDR 0, IQCODE < 3.2); and III) ""normal aging"" (N) - subjects without neuropathological AD (Braak <= II and CERAD 0 or A) and with normal cognitive function (CDR 0, IQCODE<3.2). Our results show that high levels of oxidative DNA damage are present in all groups. However, significant reductions in DNA repair and cell-cycle inhibition markers and increases in cell-cycle progression and cell death markers in subjects with CP-AD were detected when compared to both P-AD and N groups, whereas there were no significant differences in the studied markers between P-AD individuals and N subjects. This study indicates that, even in the setting of pathological AD, healthy cognition may be associated with a preserved repair to DNA damage, cell-cycle regulation, and cell death in post-mitotic neurons.
- Nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus in a Brazilian elderly cohort(2019) ZANELLA, Rosemeire Cobo; BRANDILEONE, Maria Cristina de Cunto; ALMEIDA, Samanta Cristine Grassi; LEMOS, Ana Paula Silva de; SACCHI, Claudio Tavares; GONCALVES, Claudia R.; GONCALVES, Maria Gisele; FUKASAWA, Lucila Okuyama; SARAIVA, Marcos Daniel; RANGEL, Luis Fernando; CUNHA, Julia Lusis Lassance; ROTTA, Thereza Cristina Ariza; DOURADINHO, Christian; JACOB-FILHO, Wilson; MINAMISAVA, Ruth; ANDRADE, Ana LuciaWe aimed to investigate the nasopharyngeal colonization (NPC) by Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus in the elderly population and to assess the demographic factors associated with NPC. This was an observational cohort study in which outpatients aged >= 60 years were enrolled from April to August 2017, with a follow-up visit from September through December 2017. Nasopharyngeal (NP) swabs were collected, bacteria were detected and isolated, and isolates were subjected to phenotypic and molecular characterization using standard microbiological techniques. At enrolment, the rates of S. aureus, methicillin-resistant S. aureus (MRSA), H. influenzae, and S. pneumoniae among 776 elderly outpatients were 15.9%, 2.3%, 2.5%, and 2.2%, respectively. Toxin production was detected in 21.1% of methicillin-susceptible S. aureus, and three SCCmec types were identified: II/IIb, IVa, and VI. At the follow-up visit, all carriage rates were similar (p > 0.05) to the rates at enrolment. Most of S. pneumoniae serotypes were not included in pneumococcal conjugate vaccines (PCVs), except for 7F, 3, and 19A. All strains of H. influenzae were non-typeable. Previous use of antibiotics and 23-valent pneumococcal polysaccharide vaccination (p < 0.05) were risk factors for S. aureus and MRSA carriage; S. aureus colonization was also associated with chronic kidney disease (p = 0.021). S. pneumoniae carriage was associated with male gender (p = 0.032) and an absence of diabetes (p = 0.034), while not receiving an influenza vaccine (p = 0.049) and chronic obstructive pulmonary disease (p = 0.031) were risk factors for H. influenzae colonization. The frailty of study participants was not associated with colonization status. We found a higher S. aureus carriage rate compared with the S. pneumoniae- and H. influenzae-carriage rates in a well attended population in a geriatric outpatient clinic. This is one of the few studies conducted in Brazil that can support future colonization studies among elderly individuals.
- Estimating Premorbid Cognitive Abilities in Low-Educated Populations(2013) APOLINARIO, Daniel; BRUCKI, Sonia Maria Dozzi; FERRETTI, Renata Eloah de Lucena; FARFEL, Jose Marcelo; MAGALDI, Regina Miksian; BUSSE, Alexandre Leopold; JACOB-FILHO, WilsonObjective: To develop an informant-based instrument that would provide a valid estimate of premorbid cognitive abilities in low-educated populations. Methods: A questionnaire was drafted by focusing on the premorbid period with a 10-year time frame. The initial pool of items was submitted to classical test theory and a factorial analysis. The resulting instrument, named the Premorbid Cognitive Abilities Scale (PCAS), is composed of questions addressing educational attainment, major lifetime occupation, reading abilities, reading habits, writing abilities, calculation abilities, use of widely available technology, and the ability to search for specific information. The validation sample was composed of 132 older Brazilian adults from the following three demographically matched groups: normal cognitive aging (n = 72), mild cognitive impairment (n = 33), and mild dementia (n = 27). The scores of a reading test and a neuropsychological battery were adopted as construct criteria. Post-mortem inter-informant reliability was tested in a sub-study with two relatives from each deceased individual. Results: All items presented good discriminative power, with corrected item-total correlation varying from 0.35 to 0.74. The summed score of the instrument presented high correlation coefficients with global cognitive function (r = 0.73) and reading skills (r = 0.82). Cronbach's alpha was 0.90, showing optimal internal consistency without redundancy. The scores did not decrease across the progressive levels of cognitive impairment, suggesting that the goal of evaluating the premorbid state was achieved. The intraclass correlation coefficient was 0.96, indicating excellent inter-informant reliability. Conclusion: The instrument developed in this study has shown good properties and can be used as a valid estimate of premorbid cognitive abilities in low-educated populations. The applicability of the PCAS, both as an estimate of premorbid intelligence and cognitive reserve, is discussed.
- Morphometric measurements of systemic atherosclerosis and visceral fat: Evidence from an autopsy study(2017) NISHIZAWA, Aline; SUEMOTO, Claudia K.; FARIAS-ITAO, Daniela S.; CAMPOS, Fernanda M.; SILVA, Karen C. S.; BITTENCOURT, Marcio S.; GRINBERG, Lea T.; LEITE, Renata E. P.; FERRETTI-REBUSTINI, Renata E. L.; FARFEL, Jose M.; JACOB-FILHO, Wilson; PASQUALUCCI, Carlos A.Background Morphometric measurements of systemic atherosclerosis and direct quantification of visceral fat are only possible using materials from autopsy studies. However, the few autopsy studies that have investigated the association of visceral fat with atherosclerosis had small sample sizes and focused on coronary arteries of young or middle-aged White subjects. We aimed to investigate the association of pericardial fat (PF) and abdominal visceral fat (AVF) with atherosclerosis in the aorta, coronary, carotid, and cerebral arteries in a large autopsy study. Materials and methods We evaluated deceased subjects aged 30 years or above. We dissected and weighted the PF and the AVF and evaluated the atherosclerotic burden in the aorta, as well as the carotid, coronary, and cerebral arteries using morphometric measurements. We also investigated the interaction of PF and AVF with age regarding the atherosclerotic burden. Results The mean age of the 240 included subjects was 64.8 +/- 15.3 years, and 63% was male. Greater PF was associated with a higher degree of aortic atherosclerosis after adjusting for confounding variables (coefficient = 4.39, 95% CI = 0.83; 7.94, p = 0.02). Greater AVF was associated with a higher coronary stenosis index (coefficient = 1.49, 95% CI = 0.15; 2.83, p = 0.03) and a greater number of coronary plaques (coefficient = 0.71, 95% CI = 0.24; 1.19, p = 0.003). We did not find an association of PF or AVF with carotid or cerebral atherosclerotic burden. We found a significant interaction of AVF (coefficient = -0.08; 95% CI = -0.14; -0.02, p = 0.009) and PF (coefficient = -0.87, 95% CI = -1.70; -0.04, p = 0.04) with age regarding carotid artery atherosclerotic burden. Conclusions Greater AVF was associated with greater atherosclerotic burden and extent in coronary arteries, while greater PF correlated with a higher degree of atherosclerosis in the aorta.
- Transcriptional Alterations Related to Neuropathology and Clinical Manifestation of Alzheimer's Disease(2012) SILVA, Aderbal R. T.; GRINBERG, Lea T.; FARFEL, Jose M.; DINIZ, Breno S.; LIMA, Leandro A.; SILVA, Paulo J. S.; FERRETTI, Renata E. L.; ROCHA, Rafael M.; JACOB FILHO, Wilson; CARRARO, Dirce M.; BRENTANI, HelenaAlzheimer's disease (AD) is the most common cause of dementia in the human population, characterized by a spectrum of neuropathological abnormalities that results in memory impairment and loss of other cognitive processes as well as the presence of non-cognitive symptoms. Transcriptomic analyses provide an important approach to elucidating the pathogenesis of complex diseases like AD, helping to figure out both pre-clinical markers to identify susceptible patients and the early pathogenic mechanisms to serve as therapeutic targets. This study provides the gene expression profile of postmortem brain tissue from subjects with clinic-pathological AD (Braak IV, V, or V and CERAD B or C; and CDR >= 1), preclinical AD (Braak IV, V, or VI and CERAD B or C; and CDR = 0), and healthy older individuals (Braak <= II and CERAD 0 or A; and CDR = 0) in order to establish genes related to both AD neuropathology and clinical emergence of dementia. Based on differential gene expression, hierarchical clustering and network analysis, genes involved in energy metabolism, oxidative stress, DNA damage/repair, senescence, and transcriptional regulation were implicated with the neuropathology of AD; a transcriptional profile related to clinical manifestation of AD could not be detected with reliability using differential gene expression analysis, although genes involved in synaptic plasticity, and cell cycle seems to have a role revealed by gene classifier. In conclusion, the present data suggest gene expression profile changes secondary to the development of AD-related pathology and some genes that appear to be related to the clinical manifestation of dementia in subjects with significant AD pathology, making necessary further investigations to better understand these transcriptional findings on the pathogenesis and clinical emergence of AD.
- Sexual Dimorphism in the Human Olfactory Bulb: Females Have More Neurons and Glial Cells than Males(2014) OLIVEIRA-PINTO, Ana V.; SANTOS, Raquel M.; COUTINHO, Renan A.; OLIVEIRA, Lays M.; SANTOS, Glaucia B.; ALHO, Ana T. L.; LEITE, Renata E. P.; FARFEL, Jose M.; SUEMOTO, Claudia K.; GRINBERG, Lea T.; PASQUALUCCI, Carlos A.; JACOB-FILHO, Wilson; LENT, RobertoSex differences in the human olfactory function reportedly exist for olfactory sensitivity, odorant identification and memory, and tasks in which odors are rated based on psychological features such as familiarity, intensity, pleasantness, and others. Which might be the neural bases for these behavioral differences? The number of cells in olfactory regions, and especially the number of neurons, may represent a more accurate indicator of the neural machinery than volume or weight, but besides gross volume measures of the human olfactory bulb, no systematic study of sex differences in the absolute number of cells has yet been undertaken. In this work, we investigate a possible sexual dimorphism in the olfactory bulb, by quantifying postmortem material from 7 men and 11 women (ages 55-94 years) with the isotropic fractionator, an unbiased and accurate method to estimate absolute cell numbers in brain regions. Female bulbs weighed 0.132 g in average, while male bulbs weighed 0.137 g, a non-significant difference; however, the total number of cells was 16.2 million in females, and 9.2 million in males, a significant difference of 43.2%. The number of neurons in females reached 6.9 million, being no more than 3.5 million in males, a difference of 49.3%. The number of non-neuronal cells also proved higher in women than in men: 9.3 million and 5.7 million, respectively, a significant difference of 38.7%. The same differences remained when corrected for mass. Results demonstrate a sex-related difference in the absolute number of total, neuronal and non-euronal cells, favoring women by 40-50%. It is conceivable that these differences in quantitative cellularity may have functional impact, albeit difficult to infer how exactly this would be, without knowing the specific circuits cells make. However, the reported advantage of women as compared to men may stimulate future work on sex dimorphism of synaptic microcircuitry in the olfactory bulb.
- Prognostic effects of delirium motor subtypes in hospitalized older adults: A prospective cohort study(2018) AVELINO-SILVA, Thiago Junqueira; CAMPORA, Flavia; CURIATI, Jose Antonio Esper; JACOB-FILHO, WilsonObjectives To investigate the association between delirium motor subtypes and hospital mortality and 12-month mortality in hospitalized older adults. Design Prospective cohort study conducted from 2009 to 2015. Setting Geriatric ward of a university hospital in Sao Paulo, Brazil. Participants We included 1,409 consecutive admissions of acutely ill patients aged 60 years and over. We excluded admissions for end-of-life care, with missing data on the main variables, length of stay shorter than 48 hours, or when consent to participate was not given. Main outcomes and measures Delirium was detected using the Confusion Assessment Method and categorized in hypoactive, hyperactive, or mixed delirium. Primary outcomes were time to death in the hospital, and time to death in 12 months (for the discharged sample). Comprehensive geriatric assessment was performed at admission and included socio-demographic, clinical, functional, cognitive, and laboratory variables. Further clinical data were documented upon death or discharge. Multivariate analyses used Cox proportional hazards models adjusted for possible confounders. Results We included 1,409 admissions, with a mean age of 80 years. The proportion of in-hospital deaths was 19%, with a cumulative mortality of 38% in 12 months. Delirium occurred in 47% of the admissions. Hypoactive delirium was the predominant motor subtype (53%), followed by mixed delirium (30%) and hyperactive delirium (17%). Hospital mortality rates were respectively 33%, 34% and 15%. We verified that hypoactive and mixed delirium were independently associated with hospital mortality, with respective hazard ratios of 2.43 (95%CI = 1.64-3.59) and 2.31 (95%CI = 1.53-3.50). Delirium motor subtypes were not independently predictive of 12-month mortality. Conclusions One in three acutely ill hospitalized older adults who suffered hypoactive or mixed delirium died in the hospital. Clinicians should be aware that hypoactive symptoms of delirium, whether shown exclusively or in alternation with hyperactive symptoms, are indicative of a worse prognosis in this population.