RESUMO
We studied a Cuban family with presenile dementia (autosomal dominant) consisting of 281 members within six generations, the proband descended from a Spanish founder. Mean age at onset was 59 years of age. Memory impairment was the main symptom in all patients, additionally, ischemic episodes were described in 4 (n = 18) patients. Neuropathological examination of brain material (1 patient) revealed neuronal loss, amyloid plaques, and neurofibrillary tangles. Thirty DNA samples were genotyped (regions on chromosome 1, 3, 10, 12, 14, 17, 19, 20, and 21). A maximum Lod score of 3.79 at theta = 0 was obtained for marker D14S43, located in a 9-cM interval in which all patients shared the same haplotype. Sequencing of the PSEN1 gene revealed a heterozygous base substitution, C520A (exon 6), which is predicted to cause an amino acid change from leucine to methionine in the TMIII of the presenilin 1 protein. The mutation was found to co-segregate with the disease phenotype and the associated disease haplotype. The C --> A change was not observed in 80 control chromosomes from the Cuban population. Leucine at position 174 is highly conserved among species and is identical in presenilin 1 and presenilin 2 proteins. We propose the L174 M mutation might lead to an abnormal N-terminal and probably C-terminal fragments and malfunction of the protein complex. In conclusion, we found a novel PSEN1 mutation in a large family with clinical and pathological diagnosis of early onset familial Alzheimer disease, which may be relevant for other Hispanic populations.
Assuntos
Doença de Alzheimer/genética , Proteínas de Membrana/genética , Mutação Puntual , Idade de Início , Doença de Alzheimer/patologia , Sequência de Aminoácidos , Apolipoproteínas E/genética , Sequência Conservada , Cuba , Saúde da Família , Feminino , Marcadores Genéticos , Genótipo , Hispânico ou Latino/genética , Humanos , Masculino , Dados de Sequência Molecular , Linhagem , Presenilina-1RESUMO
Due to its short half life and high tryptophan content, prealbumin has been considered a sensitive indicator of protein and/or energy deficiency. In addition, prealbumin diminishes during the acute phase response elicited by either infection or tissue injury. Serum levels of prealbumin were determined in undernourished children with or without associated clinical infection and in their infected or non-infected controls matched for age, sex, race and socioeconomical conditions. Serum levels of prealbumin were significantly lower in undernourished than in control children without overt infections. On the other hand, the concentrations of serum prealbumin diminished significantly and to similar levels both in undernourished and control children with associated clinical infection as compared with those observed in non infected children belonging to the similar nutritional status. A positive correlation was found between prealbumin level and the Z-scores of weight-for-age, height-for-age and weight-for height in children without associated infections, which disappeared in clinically infected patients. Thus, prealbumin is a marker of undernutrition in the absence of infection and could be an earlier and more sensitive indicator of actual undernutrition caused by the metabolic effects of acute phase cytokines, than the anthropometrical measurements used here.
Assuntos
Infecções/sangue , Estado Nutricional , Pré-Albumina/análise , Pré-Escolar , Feminino , Humanos , Lactente , MasculinoRESUMO
The present trial has been conducted in order to determine familia aggregation and the relationship between high blood pressure, inheritance and environmental factors. We studied 108 subjects (36 high blood pressure patients, 36 controls and 36 first degree relatives) ranging in age from 21 to 55 years. This case-control study was undertaken to determine risk factors. Multivariance analysis with logistic regression was carried out. Our results showed hereditary factors in 73.8% of the cases. Being the main gene autosomal recessive. Thus the main factor for high pressure is hereditary predisposition. Others factor are, body mass index and the coefficient waist-hip. We found no correlation with serum lipids.
Assuntos
Saúde Ambiental , Hipertensão/genética , População Urbana , Adulto , Antropometria , Estudos de Casos e Controles , Intervalos de Confiança , Cuba , Saúde Ambiental/estatística & dados numéricos , Feminino , Humanos , Hipertensão/sangue , Hipertensão/etiologia , Lipídeos/sangue , Lipoproteínas/sangue , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Linhagem , Fatores de Risco , População Urbana/estatística & dados numéricosRESUMO
We have studied the influence of the oral administration of excess copper (Cu) on the immune response. With this aim, mice maintained on standard laboratory diet received 50, 100, 200, or 300 ppm of Cu as copper sulfate in the drinking water during 3 to 10 weeks. Inhibition of the proliferative response to concanavalin A was observed in mice exposed to 100 ppm of Cu for 8 weeks and to 200 ppm of Cu for either 3 or 8 weeks. Conversely, a significant increase in the proliferative response to Escherichia coli lipopolysaccharide (LPS) was observed in mice exposed to 50 or 100 ppm of Cu for 3 weeks. However, the response to LPS was also significantly inhibited following prolonged Cu administration. In contrast, mice exposed to low or high Cu doses during short or long periods showed increased production of autoantibodies directed to bromelain-treated mouse erythrocytes. The DTH response to sheep red blood cells was not modified following short-term administration of 100 ppm of Cu, but was depressed after prolonged exposure to this dose of the metal. Significant inhibition of the DTH response was observed in mice exposed to 300 ppm of Cu for 5 or 10 weeks. Thus, oral administration of excess Cu altered the immune response in a fashion related to the dose and duration of treatment.
Assuntos
Cobre/intoxicação , Sistema Imunitário/efeitos dos fármacos , Administração Oral , Animais , Formação de Anticorpos/efeitos dos fármacos , Autoanticorpos/biossíntese , Sulfato de Cobre , Eritrócitos/imunologia , Feminino , Hipersensibilidade Tardia/imunologia , Ativação Linfocitária/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitógenos/farmacologiaRESUMO
To study if treatment with zinc (Zn) was able to restore to normal levels the depressed immune response determined by oral administration of excess copper (Cu), groups of mice receiving 100 ppm or 200 ppm of Cu in the drinking water for 8 weeks, were injected ip once a week with Zn (1.14 mg/kg of body weight), throughout the experimental period. Administration of Zn restored to normal levels the proliferative response to mitogens and the antibody response to sheep red blood cells in the group of mice receiving 100 ppm of Cu in the drinking water. Similarly, the treatment with Zn significantly enhanced the depressed proliferative response to mitogens and the antibody response to sheep red blood cells of mice receiving 200 ppm of Cu in the drinking water. By contrast, increment in Zn supply was not able to modify the high production of auto-antibodies observed in animals receiving excess Cu. The results suggest that the impairment of the immune response observed in animals receiving excess Cu could be in part due to antagonistic interactions between this cation and Zn.
Assuntos
Cobre/toxicidade , Imunidade/efeitos dos fármacos , Zinco/farmacologia , Administração Oral , Animais , Formação de Anticorpos/efeitos dos fármacos , Autoanticorpos/biossíntese , Cobre/administração & dosagem , Feminino , Ativação Linfocitária/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Zinco/deficiênciaRESUMO
We have studied the influence of different degrees of calorie restriction on the induction and the regulation of the delayed type hypersensitivity (DTH) response to trinitrobenzenesulfonic acid (TNBS) and TNBS-modified spleen cells (TNBS-SC), injected by the sc or the iv route. Immediately after weaning, BALB/c mice were placed on restricted diets for either 2 or 4 weeks and then the DTH response was induced. The results showed that a 37.5% restriction in the food supply significantly depressed the level of the DTH response induced by the sc injection of TNBS-SC. In contrast, a 25% restriction in the food supply was insufficient to depress the response. Calorie restriction did not modify the inhibitory influence of an iv injection of TNBS-SC on the DTH response. However, iv presensitization with free hapten or the simultaneous injection of TNBS-SC by the iv and the sc routes did not significantly depress the DTH response in calorie-restricted mice, indicating a defect in the inhibitory regulation of the DTH response in these dietary groups.