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1.
Psychol Res ; 84(2): 370-379, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30073408

RESUMO

The present study addresses a novel issue by investigating whether beholders' sensorimotor engagement with the emotional content of works of art contributes to the formation of their objective aesthetic judgment of beauty. To this purpose, participants' sensorimotor engagement was modulated by asking them to overtly contract the Corrugator Supercilii facial muscles or to refrain from any voluntary facial movement while judging the aesthetic value of painful and neutral facial expressions in select examples of Renaissance and Baroque paintings. Results demonstrated a specific increase in the aesthetic rating of paintings showing painful facial expressions during the congruent activation of the Corrugator Supercilii muscles. Furthermore, participants' empathetic traits and expertise in art were found to correlate directly with the amplitude of the motor enactment effect on aesthetic judgments. For the first time, we show the role of bottom-up bodily driven sensorimotor processes in the objective aesthetic evaluation of works of art.


Assuntos
Estética , Expressão Facial , Músculos Faciais/fisiologia , Contração Muscular/fisiologia , Dor/psicologia , Adulto , Emoções/fisiologia , Feminino , Humanos , Julgamento/fisiologia , Masculino , Estimulação Luminosa , Adulto Jovem
2.
Phys Chem Chem Phys ; 19(32): 21287-21296, 2017 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-28597880

RESUMO

The p53 tumour suppressor is a transcription activator that signals for cell cycle arrest and apoptosis. In its active form p53 is a tetramer, with each monomer organised in domains with different degrees of structural stability, ranging from the well folded DNA-binding domain (DBD) and tetramerization domain (TET), to the intrinsically disordered transactivation domain (TAD), and extreme C-terminal domain (CTD). Compared to all other domains, the structure/function relationship of the p53-CTD within the full-length p53 tetramer is still poorly understood due to its high degree of conformational disorder. Meanwhile, the structure of p53-CTD-like peptides has been well characterized when in complex with a variety of receptors, where, as other intrinsically disordered regions (IDR), it adopts specific, while diverse, conformations. Receptor-specific folding is likely to occur upon binding, either from a random coil, or as a result of an initial recognition of a pre-formed structural motif, known as molecular recognition feature (MoRF), selected by the receptor within the conformational ensemble of the IDP in solution. In this latter case, MoRFs act as nucleation sites, favouring the initiation of the folding process within the binding site. In this work we show the results of over 20 µs of cumulative molecular dynamics (MD) simulations of a 22 residue peptide unbound in solution with sequence corresponding to the p53-CTD 367-388 section. Such extensive sampling allowed us to identify and characterize the structure of specific sets of minimal structural MoRFs within the p53-CTD peptide conformational ensemble at equilibrium. These motifs are short, involving only 3 to 4 residues, and specifically localized within the peptide sequence. Corresponding patterns of secondary structure propensity along the p53-CTD sequence are also predicted by disorder prediction calculations. Based on these findings we discuss how the structural complementarity of specific minimal structural MoRFs to the binding site of different receptors could regulate the p53-CTD binding promiscuity.


Assuntos
Simulação de Dinâmica Molecular , Proteína Supressora de Tumor p53/química , Sequência de Aminoácidos , Ligação Proteica , Domínios Proteicos , Estrutura Secundária de Proteína , Subunidade beta da Proteína Ligante de Cálcio S100/química , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo , Proteína Supressora de Tumor p53/metabolismo
3.
Vaccine ; 27(4): 588-91, 2009 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-19010368

RESUMO

BCG vaccine, vaccinia vaccine and certain pathogens that were shown in previous studies to protect against melanoma have antigenic determinants homologous in their amino acids sequence with the melanoma antigen HERV-K-MEL, encoded by a human endogenous retrovirus K (HERV-K), which is expressed in about 95% of malignant melanocytes. Yellow fever vaccine (YFV) likewise contains an antigenic determinant with a close homology to HERV-K-MEL and might therefore also confer protection against melanoma. To investigate this possibility we carried out a cohort study (28,306 subjects) and a nested case-control study (37 melamona cases and 151 tumors not expressing HERV-K-MEL) in Veneto region (North-Eastern Italy). The standardized incidence ratio was 1.33 (95% confidence interval, 0.84-2.11), 1.59 (0.97-2.59) and 0.59 (0.19-1.84), while the age- gender-adjusted odds ratios were 1.00, 0.96 (0.43-2.14) and 0.26 (0.07-0.96), at 0-4, 5-9, and > or =10 years elapsed from YFV administration, respectively. The risk of melanoma may therefore be lowered 10 years after vaccination with yellow fever vaccine.


Assuntos
Melanoma/imunologia , Melanoma/prevenção & controle , Vacina contra Febre Amarela/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Virais/imunologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Melanoma/genética , Pessoa de Meia-Idade , Vacina contra Febre Amarela/genética , Adulto Jovem
4.
Ann Occup Hyg ; 53(2): 161-5, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19109442

RESUMO

OBJECTIVES: Two cross-sectional studies were undertaken on workers in a beverage processing plant to investigate the association between low H(2)O(2) exposure and symptoms of irritation (2005 study) and to investigate the effect of wearing respiratory protection (2006 study). METHODS: The study comprised 69 workers exposed to H(2)O(2) in sterile chambers and 65 unexposed controls. The exposure was assessed from measurements and work task information from employment records. The severity of work-related symptoms was evaluated using questionnaires. Data were analyzed by the Student's t-test, multiple linear regression and analysis of variance for repeated measures of symptoms. RESULTS: Symptoms of eye, nose and throat irritation were significantly (P < 0.001) more severe among exposed workers compared to controls. Exposure values were occasionally above American Conference of Governmental Industrial Hygienists (ACGIH) threshold limit value-time-weighted average (TLV-TWA) in the sterile chambers. The relationship between the severity of symptoms and the number of entrances in the chambers was significant (P < 0.0001) in 2005 but not in 2006, when respirators were used during work in the sterile chamber. No differences were found between exposed who entered a sterile chamber in 2005 but not in 2006 and exposed who entered a sterile chamber both in 2005 and 2006. This suggests that respirators provided an efficient protection and that the irritative effects of exposure to H(2)O(2) in 2005 did not disappear after 1 year. CONCLUSIONS: The source of risk was exposure in the sterile chamber, even though the time of exposure was generally only approximately 30 min. To ensure complete worker protection, there is a need for a short-term exposure limit for H(2)O(2) in addition to the existing ACGIH TLV-TWA value.


Assuntos
Bebidas , Indústria Alimentícia , Peróxido de Hidrogênio/efeitos adversos , Irritantes/efeitos adversos , Exposição Ocupacional/análise , Adulto , Estudos de Casos e Controles , Conjuntivite/induzido quimicamente , Conjuntivite/prevenção & controle , Estudos Transversais , Feminino , Humanos , Peróxido de Hidrogênio/análise , Irritantes/análise , Modelos Lineares , Masculino , Saúde Ocupacional , Dispositivos de Proteção Respiratória , Rinite/etiologia , Rinite/prevenção & controle , Risco
5.
Med Hypotheses ; 71(4): 551-63, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18614293

RESUMO

The basis of World Health Organization strategy for leprosy elimination is that the only source and reservoir for infection are patients with the disease. It was assumed that multi drug therapy (MDT) would reduce transmission of Mycobacterium leprae, but there is no convincing evidence for this. Furthermore, even if MDT has been proved to be extremely effective against the infectious disease, a noticeable proportion of leprosy patients can suffer from immunologic hypersensitivity reactions which are now the most significant issue in the managements of the disease. In endemic areas it was found that: M. leprae survives outside human body; healthy individuals harbor M. leprae bacilli in nasal cavity and shed micro-organisms in environment; there is widespread subclinical transmission of M. leprae with transient infection of the nose resulting in the development of a mucosal immune response. This disparate clinical, epidemiologic, and microbiologic evidence leads to the first hypothesis: that antigenic load in local tissues, sufficient to trigger the immune response, comes from external supply of M. leprae organisms. The hypothiocyanite anion (OSCN-) is generated in vivo by the reaction of thiocyanate with hydrogen peroxide catalyzed by lactoperoxidase. OSCN- is an antimicrobial oxidizing agent that prevents growth of bacteria, fungi, and viruses. OSNC- exists in lower airway secretions and lung has never been reported to be affected by leprosy. There is a sufficient concentration of OSCN- in the saliva, and accordingly mouth is rarely affected by leprosy. By contrast, the concentration of this compound is low or nil in nasal and lacrimal secretions and leprosy very often affects nose and eyes. The second hypothesis is that OSCN- may also protect from leprosy. Recently a method of OSCN- production, not involving enzymatic steps or use of toxic heavy-metal salts, has been patented. Studies on the susceptibility of M. leprae to hypothiocyanite could be carried out and, in case of positive results, the substance might be used in order to sterilize the nasal cavity of healthy carriers and prevent transmission of M. leprae to healthy subjects and to leprosy patients in whom it may trigger an immune response.


Assuntos
Hanseníase/transmissão , Mycobacterium leprae/isolamento & purificação , Humanos , Peróxido de Hidrogênio/metabolismo , Lactoperoxidase/metabolismo , Hanseníase/imunologia , Hanseníase/microbiologia , Modelos Teóricos , Fatores de Risco , Tiocianatos/metabolismo
6.
Occup Environ Med ; 65(10): 697-700, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18417554

RESUMO

BACKGROUND: Several studies report a lower than expected mortality in lung cancer among workers exposed to organic dust. Recent studies also reported a decreased risk for cancer at other sites. OBJECTIVES: To evaluate the mortality from lung and other cancer sites in cotton mill workers. MATERIAL AND METHODS: A cohort of 3961 Italian cotton mill workers was divided into those working with carding (exposed to high levels of endotoxin-containing cotton dust) and other tasks, which generally have lower exposure. Standardised mortality ratios (SMRs), with 95% confidence intervals (CI), were calculated using death rates of the regional general population as a reference. Cancer mortality was analysed in relation to the length of employment in the two task groups. An internal analysis was also performed through Poisson regression. RESULTS: Among workers in carding departments, lung cancer SMRs were 1.88 (CI: 0.69 to 4.08), 1.01 (CI: 0.20 to 2.94) and 0.22 (CI: 0.00 to 1.24), respectively, for <6, 6-12 and >12 years of employment (chi(2) for trend = 5.45; p<0.05). A significant (p = 0.04) trend was confirmed by Poisson regression. No reduced risks were found for other forms of cancer, nor for those working with other tasks. CONCLUSIONS: The results support previous reports that a high and prolonged exposure to cotton dust and other endotoxin-containing organic dusts is related to a lower risk of lung cancer. There was no indication of a reduced risk for other forms of cancer.


Assuntos
Fibra de Algodão , Endotoxinas/toxicidade , Neoplasias/mortalidade , Indústria Têxtil/estatística & dados numéricos , Adulto , Distribuição por Idade , Idoso , Causas de Morte/tendências , Estudos de Coortes , Poeira , Humanos , Itália/epidemiologia , Neoplasias Pulmonares/mortalidade , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
7.
Gynecol Oncol ; 107(1 Suppl 1): S175-9, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17825395

RESUMO

OBJECTIVE: To evaluate the impact of the communication of an HPV diagnosis on the cognitive-behavioural aspect, emotional experiences, psychic-physical well-being, and psychosexual sphere in young women between the ages of 20 and 45. METHOD: During the period between February 2006 and March 2007, at the U.O. Department of Obstetrics and Gynecology of the ULSS 13 of Mirano (VE), we distributed three self-evaluating questionnaires (the CBA-20, the SAT-P, and the BISF-W) to 36 women who had been diagnosed with an HPV infection and 36 women who had never been diagnosed with HPV. RESULTS: 36% of the experimental group reacted to the diagnosis with fear and 29% reacted with anxiety, while in only 3% of the cases did the women react with anger. Significant differences emerged in two samples regarding state anxiety and obsessive and compulsive aspects, while there were no significant differences between the two groups regarding the subjective satisfaction with life quality and sexual function. A significant positive correlation was found between the sum of anxiety and fear expressed at the time of the diagnosis and the trait anxiety reported in the Cognitive Behavioural Assessment 2.0. CONCLUSIONS: The results indicate that the prevalent emotions felt at the time of the diagnosis are fear and anxiety. The persons who were diagnosed with an HPV infection resulted as having higher levels of trait anxiety, obsessions, compulsions, and above all, behaviours and worries related to hygiene and improbable infections.


Assuntos
Infecções por Papillomavirus/psicologia , Adulto , Transtornos Cognitivos/virologia , Comunicação , Feminino , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Sexualidade/psicologia , Revelação da Verdade
8.
Int J Environ Health Res ; 15(4): 313-7, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16175747

RESUMO

This study reports on longitudinal changes in lung function using spirometry of employees at a beverage processing plant, where exposure information (1995-2001) suggests that the threshold limit value (TLV)-Time Weighted Average (TWA) of 1 ppm was not likely exceeded. Changes over time in lung function (Forced Expiratory Volume of 1st second, FEV1; Forced Vital Capacity, FVC; and FEV1/FVC ratio; all expressed as percent of the predicted) were evaluated by using sparse lung function data obtained from 1993 to 2002 in 43 exposed and 31 unexposed workers. The longitudinal changes were assessed using multiple regression analysis where the dependent variable was the annual change of lung function indices and the independent variables were exposure and smoking habits. With regard to exposure, FVC increased, FEV1 was unchanged, and the FEV1/FVC ratio tended to decrease. The latter difference was not significant when FVC was used as a covariate. The FEV1 is significantly worse in smokers than in non-smokers. These data suggest that no lung function changes occur when the H2O2 levels were compliant to the exposure standard. Our findings support the current TLV-TWA of 1 ppm for H2O2.


Assuntos
Peróxido de Hidrogênio/efeitos adversos , Pneumopatias/etiologia , Oxidantes/efeitos adversos , Níveis Máximos Permitidos , Adulto , Bebidas , Feminino , Humanos , Indústrias , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Fumar
9.
Med Hypotheses ; 65(3): 534-41, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15913904

RESUMO

Several reports indicate that the risk of lung cancer increases slightly for a short period of time after cessation of smoking while the risk of adverse cardiovascular events drops immediately. Recent studies on subjects occupationally exposed to organic dust-containing endotoxin have revealed lower than expected rates of lung cancer. There is experimental evidence that stimulation of the immune system by endotoxin has a protective effect against cancer. Tobacco smoke has been shown to contain high levels of endotoxin. We therefore postulate that cessation of smoking eliminates the protective effect of endotoxin. Any benefit conferred by endotoxin does not, however, justify smoking. As the inverse relationship between exposure to endotoxin and the risk of lung cancer is a strong one, endotoxin-like substances could form the basis of vaccination strategies.


Assuntos
Endotoxinas , Neoplasias Pulmonares/etiologia , Abandono do Hábito de Fumar , Endotoxinas/efeitos adversos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/prevenção & controle , Fatores de Risco
10.
Int J Immunopathol Pharmacol ; 16(2): 145-50, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12797905

RESUMO

Inhalation of polyaromatic hydrocarbons (PAHs) extracted from diesel exhaust particles (DEP) enhances local (nasal) production of IgE in humans. The aim of the present research is to investigate whether in humans dermal exposure to PAHs which are not extracted from DEPs increases serum IgE, and whether host factors modify the immunologic effect. In thirty-two patients with acute psoriatic lesions, a cream containing 3% of coal tar (which holds a variety of PAHs) was applied to the skin for 24 hours. Serum IgE were measured before (IgE0) and four (IgE4) and eight (IgE8) days after application. Replicated means were compared by analysis of variance for repeated measures and by the Newman-Keuls' test. IgE0, IgE4 and IgE8 were 151.19, 159.69 (a 6% excess) and 170.90 kU/L (a 13% excess) respectively; pairwise comparison showed IgE8 was significantly higher than IgE0 (p<0.05). At multiple linear regression analysis, the percentage increase in serum IgE across observation days was the dependent variable against age, sex, cigarettes/day, urinary 1-pyrenol, atopy, skin area treated, and grams of cream. Of the independent variables, only age had a significant (p<0.028) influence: the younger the age, the higher the IgE response to PAHs. We conclude that whatever the source and the route of entry (skin or respiratory tract), PAHs increase total serum IgE, mainly in younger age groups.


Assuntos
Imunoglobulina E/sangue , Hidrocarbonetos Policíclicos Aromáticos/administração & dosagem , Administração Cutânea , Adulto , Fatores Etários , Idoso , Análise de Variância , Feminino , Humanos , Imunoglobulina E/biossíntese , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Hidrocarbonetos Policíclicos Aromáticos/imunologia
11.
Occup Environ Med ; 60(6): 423-8, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12771394

RESUMO

BACKGROUND: There have been few investigations of an association between poly(vinyl chloride) (PVC) dust exposure and an increase in lung cancer incidence, and their conclusions have been inconsistent. AIMS: To determine whether PVC and/or vinyl chloride monomer (VCM) is the associated risk factor(s), by means of a nested case-referent study, in order to estimate lung cancer risk, avoiding selection, information, or confounding biases. METHODS: Thirty eight cases of histologically verified lung cancer and 224 control subjects without a history of cancer were selected from an Italian cohort of 1658 vinyl chloride workers. Information sources included clinical records (diagnosis, smoking habits) and plant records (occupational history). The risk of lung cancer was estimated by odds ratios (OR) with 95% confidence intervals (CI), calculated using logistic regression models. RESULTS: In PVC baggers exposed to high levels of respirable PVC particles in the workplace, the lung cancer OR increases by 20% for each extra year of work (OR = 1.2003; 95% CI 1.0772 to 1.3469; p = 0.0010), when the influence of age and smoking habits is controlled. No relation was found between lung cancer and cumulative VCM exposure. CONCLUSION: This nested case-control study showed, in the VCM/PVC industry, an increased risk of lung cancer associated with exposure to PVC dust; previous cohort studies failed to recognise such excess, probably because they used VCM exposure as the risk indicator.


Assuntos
Neoplasias Pulmonares/induzido quimicamente , Doenças Profissionais/induzido quimicamente , Cloreto de Polivinila/efeitos adversos , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Poeira , Fatores Epidemiológicos , Humanos , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Tamanho da Partícula , Fumar/efeitos adversos
12.
Occup Med (Lond) ; 53(3): 165-72, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12724550

RESUMO

BACKGROUND: Recent community surveys have reported a risk of chronic obstructive pulmonary disease (COPD) in occupations involving exposure to organic dust and gas/vapour. Aims Our aim was to confirm these results using a case-control design on 131 COPD cases (FEV(1) < 80% of predicted value, minimally reversible with bronchodilators) and 298 controls, selected from registers for patients admitted to our Institute of Occupational Medicine. METHODS: Surrogates of past exposure were occupation, exposure assigned by a job-exposure matrix, and years spent in a given occupation. The odds ratio (OR) and 95% confidence interval (CI) for COPD were calculated using logistic regression models with office workers as the reference. RESULTS: Age-smoking-adjusted ORs (and CIs) were: 15.1 (3.2-71.6) in farmers; 7.2 (1.3-41.1) in cotton workers; 6.4 (1.6-25.5) in welders; 4.7 (1.3-16.4) in painters; 12.1 (1.3-108) in foundry workers; 6.50 (1.14-37.0) in refractory brick workers; and 3.1 (1.0-9.5) in construction workers. In farmers, cotton workers, welders and painters, the adjusted ORs significantly increased (by 6-9%) for each extra year of work, while in other occupations any such increase was of borderline significance. Adjusted ORs were 3.80 (1.21-12.0), 5.83 (1.82-18.6) and 8.86 (2.29-34.3) in workers exposed to high levels of mineral dust, gas/vapour/fume and biological dust, respectively. Consistent risk estimates were obtained for farmers, textile workers, painters and welders. CONCLUSIONS: Our findings confirm previous epidemiological evidence and are supported by recent observations that cigarette smoke, cotton and organic farm dust contain the same powerful pro-inflammatory agents, and that organic dust and irritant gas induce bronchitis by triggering the same effector molecules as cigarette smoke.


Assuntos
Poeira , Gases/efeitos adversos , Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/etiologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Itália/epidemiologia , Modelos Logísticos , Masculino , Doenças Profissionais/epidemiologia , Razão de Chances , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fatores de Risco , Fumar/efeitos adversos
13.
G Ital Med Lav Ergon ; 25 Suppl(3): 77-8, 2003.
Artigo em Italiano | MEDLINE | ID: mdl-14979092

RESUMO

In the bottling departments of a beverage processing plant, exposure to hydrogen peroxide was below TLV from 1995 to 2001. Forced vital capacity (FVC), forced expiratory volume 1st second (FEV1), and FEV1/FVC were compared between exposed and unexposed workers. Using sparse data collected from 1993 to 2002, changes over time (slope) were calculated for each functional index in each subject. The slope was the dependent variable at multiple regression analysis with exposure and smoking as predictive variables. Using complete data collected from 2000 to 2002 in fewer subjects, the longitudinal changes were assessed by repeated measures analysis of variance. Both methods provide same results: with respect to unexposed, in exposed workers FVC increased, FEV1/was unchanged and FEV1/FVC decreased; the latter difference was no more significant when FVC slope was added as covariate to the model. In conclusion, the findings seem to support the current TLV for hydrogen peroxide. There were no similar studies in the literature.


Assuntos
Volume Expiratório Forçado , Peróxido de Hidrogênio/toxicidade , Exposição Ocupacional/efeitos adversos , Capacidade Vital , Humanos , Estudos Longitudinais , Níveis Máximos Permitidos
14.
G Ital Med Lav Ergon ; 25 Suppl(3): 79-80, 2003.
Artigo em Italiano | MEDLINE | ID: mdl-14979093

RESUMO

Risk factors of spontaneous abortion were investigated in two matched case-control studies in 1987-88 and 1997-99. An history of previous abortions significantly increased the risk in both studies. Lifestyle (coffee) and occupational (exposure to organic solvents) factors were associated with a significantly increased risk in the first but not in the second calendar period, following a community intervention with advice given to workers, employers, and physicians; the latter also counseled a greater use of medicines against spontaneous abortion.


Assuntos
Aborto Espontâneo/prevenção & controle , Exposição Ambiental/efeitos adversos , Aborto Espontâneo/etiologia , Feminino , Humanos , Itália , Gravidez , Fatores de Risco , Sapatos
15.
Hum Mol Genet ; 10(25): 2907-16, 2001 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-11741834

RESUMO

Several studies have indicated that multiple sclerosis (MS) is associated and linked to the major histocompatibility complex (MHC)/human leukocyte antigen (HLA) region of chromosome 6p21.3, but the exact location and nature of the primarily associated locus within the HLA complex is still controversial and largely presumptive. By linkage disequilibrium mapping, we have systematically investigated this chromosome region in the founder population of Sardinia to determine the relative associations of the various loci with MS. An overall 11.4 Mb region, which encompasses the whole HLA complex, was scanned with 19 microsatellite markers and with single nucleotide polymorphisms within 12 functional candidate genes and assessed for MS association using the extended transmission disequilibrium test (ETDT). A peak of association represented by the three adjacent DRB1, -DQA1 and -DQB1 loci was detected in the class II region. Two additional less significant areas of association were detected, respectively, in the centromeric side of the class II region at the DPB1 locus and, telomeric of the classically defined class I loci, at the D6S1683 microsatellite. Conditional ETDT analysis indicated that these regions of association could be independent of each other. Within the main peak of association, DRB1 and DQB1 contribute to the disease association independently of each other whereas DQA1 had no detectable primary genetic effects. We evaluated the haplotype distribution at the region showing the strongest association and found five DQB1-DRB1 haplotypes positively associated with MS in Sardinia. These consistently included all the haplotypes previously found associated with MS in the various human populations, thus supporting a primary effect of the products of these loci in MS. Overall these results are consistent with a multilocus model of the MHC encoded susceptibility to MS.


Assuntos
Cromossomos Humanos Par 6/genética , Antígenos HLA-DP/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Esclerose Múltipla/genética , Adolescente , Adulto , Idoso , Alelos , Criança , Feminino , Efeito Fundador , Variação Genética , Cadeias beta de HLA-DP , Cadeias beta de HLA-DQ , Cadeias HLA-DRB1 , Humanos , Itália , Desequilíbrio de Ligação , Masculino , Repetições de Microssatélites , Pessoa de Meia-Idade
16.
J Neurol ; 247(9): 677-80, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11081805

RESUMO

An increased amount of the intercellular adhesion molecule (ICAM) 1 molecule has been found in the blood of actively relapsing multiple sclerosis (MS) patients, but is unclear whether this enhanced expression is partially causative of the MS process, or whether it is merely an epiphenomenon of the inflammatory-immunological reaction. Using the transmission disequilibrium test (TDT), we studied exon 4 and exon 6 polymorphism of the ICAM-1 gene from 157 families with both parents, one affected and one healthy sib coming from Sardinia, an Italian island having a high incidence and prevalence of MS. TDT did not show variation in the expected 50:50 frequency in transmission in either healthy or affected sibs, using phenotypic or genotypic analysis. Moreover, independence from the predisposing HLA-DRB1-DQA1-DQB1 haplotype was confirmed by TDT analysis performed on patients stratified according to the presence or absence of the HLA-DRB1, DQA1, DQB1 Sardinian predisposing haplotypes. Our data suggest that the increased expression of the ICAM-1 molecule observed in both blood and periplaque microvessels may be considered a consequence of the inflammatory process rather than the result of a genetic variation.


Assuntos
Molécula 1 de Adesão Intercelular/genética , Esclerose Múltipla/genética , Adulto , Progressão da Doença , Feminino , Humanos , Molécula 1 de Adesão Intercelular/biossíntese , Molécula 1 de Adesão Intercelular/sangue , Itália , Masculino , Microcirculação , Esclerose Múltipla/patologia , Linhagem , Polimorfismo Genético
19.
Eur J Epidemiol ; 16(9): 777-82, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11297217

RESUMO

The aim of the present case-control study was to ascertain whether, in adults, yearly repeated anti-influenza vaccinations (AIV) enhance protection against cutaneous melanoma (CM), as do repeated febrile infections. Ninety-nine new cases of histologically confirmed CM and 104 healthy controls (matched to cases for sex, age, and skin colour) selected from the general population were examined in order to ascertain their skin type, the number of nevi on both arms, and the intensity of freckles on the face and the arms; in these subjects, a structured questionnaire was used to obtain information on age, sex, education, social class, exposure and susceptibility to sunlight, history of febrile infectious diseases, and vaccinations. The odds ratio (OR) and the 95% confidence interval (CI) were estimated by commonly used methods and by fitting models of logistic regression. The risk of CM was reduced in subjects with a history of febrile (temperature above 38.5 degrees C) infections in the 5 years prior to CM surgery (cases) or interview (controls), but was increased in those with voluntary exposure to sunlight in tropical countries. By holding the above factors constant at logistic regression analysis, it was found that a history of repeated AIV (3-5 times in the last 5 years) halved the risk (OR: 0.43; CI: 0.19-1.00; p < 0.05). With the variable 'nevi on arms' included, the protective influence of repeated AIVs was observed in a similar magnitude. The inverse relationship found between melanoma and influenza vaccinations is unlikely to have depended on a bias, even if based on replies in a questionnaire, because neither the interviewers nor the interviewers were informed in advance of the working hypothesis.


Assuntos
Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Melanoma/prevenção & controle , Neoplasias Cutâneas/prevenção & controle , Vacinação , Adulto , Estudos de Casos e Controles , Intervalos de Confiança , Feminino , Febre/imunologia , Humanos , Itália/epidemiologia , Modelos Logísticos , Masculino , Melanoma/epidemiologia , Melanoma/patologia , Razão de Chances , Prevalência , Fatores de Risco , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Fatores Socioeconômicos , Luz Solar/efeitos adversos , Inquéritos e Questionários , Fatores de Tempo
20.
Eur J Epidemiol ; 14(8): 749-54, 1998 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9928868

RESUMO

Two rate ratios indicating the disappearance of infections and the growth of tumours, respectively, were simultaneously plotted against the calendar years of occurrence in a period during which mortality rates were reasonably comparable to incidences. The transformation used gave upward trend time variations for infectious diseases, providing strong evidence that in Italy during the first half of this century variations in infectious diseases preceded variations in cancer. While some bacteria and viruses are known to be cancer agents, sparse studies indicate that a host's immune response to infection may destroy cancer cells. With a decreasing mortality from infectious illnesses, there may have been a reduction in the activation of immunological mechanisms against transformed cells in early phases of carcinogenesis. If cancer growth is a consequence of a lower exposure to chronic sublethal doses of microbial agents, bacterial derivates could be potentially useful in cancer chemoprevention.


Assuntos
Doenças Transmissíveis/epidemiologia , Neoplasias/epidemiologia , Adulto , Algoritmos , Infecções Bacterianas/imunologia , Transformação Celular Neoplásica/imunologia , Quimioprevenção , Controle de Doenças Transmissíveis , Doenças Transmissíveis/etiologia , Doenças Transmissíveis/imunologia , Doenças Transmissíveis/mortalidade , Feminino , Humanos , Incidência , Itália/epidemiologia , Modelos Lineares , Masculino , Neoplasias/etiologia , Neoplasias/imunologia , Neoplasias/mortalidade , Neoplasias/prevenção & controle , Fatores Sexuais , Fumar/epidemiologia
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