RESUMO
Gaucher disease (GD) is caused by pathogenic mutations in GBA1, the gene that encodes the lysosomal enzyme ß-glucocerebrosidase. Until now, treatments for GD cannot completely reverse bone problems. The aim of this work was to evaluate the potential of MSCs from GD patients (GD MSCs) to differentiate towards the osteoblast (GD Ob) and adipocyte (GD Ad) lineages, and their role in osteoclastogenesis. We observed that GD Ob exhibited reduced mineralization, collagen deposition and alkaline phosphatase activity (ALP), as well as decreased gene expression of RUNX2, COLA1 and ALP. We also evaluated the process of osteoclastogenesis and observed that conditioned media from GD MSCs supernatants induced an increase in the number of osteoclasts. In this model, osteoclastogenesis was induced by RANKL and IL-1ß. Furthermore, results showed that in GD MSCs there was a promotion in NLRP3 and PPAR-γ gene expression. Adipogenic differentiation revealed that GD Ad had an increase in PPAR-γ and a reduced RUNX2 gene expression, promoting adipocyte differentiation. In conclusion, our results show that GD MSCs exhibited deficient GD Ob differentiation and increased adipogenesis. In addition, we show that GD MSCs promoted increased osteoclastogenesis through RANKL and IL-1ß. These changes in GD MSCs are likely to contribute to skeletal imbalance observed in GD patients.
Assuntos
Adipogenia , Diferenciação Celular , Doença de Gaucher/patologia , Glucosilceramidase/deficiência , Células-Tronco Mesenquimais/patologia , Osteoclastos/patologia , Osteogênese , Apoptose , Ciclo Celular , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Doença de Gaucher/metabolismo , Regulação da Expressão Gênica , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Células-Tronco Mesenquimais/metabolismo , Osteoclastos/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Ligante RANK/genética , Ligante RANK/metabolismoRESUMO
Nucleotide sequences at two mitochondrial genes from 57 individuals representing eight species of deep-sea clams (Vesicomyidae) were examined for variation consistent with the neutral model of molecular evolution. One gene, cytochrome oxidase subunit I (COI), deviated from the expectations of neutrality by containing an excess of intraspecific nonsynonymous polymorphism. Additionally, one species, Calyptogena kilmeri, showed a significant excess of rare polymorphism specifically at the COI locus. In contrast, a second mitochondrial gene, the large-subunit 16S ribosomal RNA gene (16S), showed little deviation from neutrality either between or within species. Together, COI and 16S show no deviation from neutral expectations by the HKA test, produce congruent phylogenetic relationships between species, and show correlated numbers of fixed differences between species and polymorphism within species. These patterns of both neutral and nonneutral evolution within the mitochondrial genome are most consistent with a model where intraspecific nonsynonymous polymorphism at COI is near neutrality. In addition to examining the forces of molecular evolution, we extend hypotheses about interspecific relationships within this family for geographical locations previously unexamined by molecular methods including habitats near the Middle Atlantic, the Aleutian Trench, and Costa Rica.
Assuntos
Bivalves/genética , Variação Genética , Mitocôndrias/genética , Filogenia , Animais , Costa Rica , DNA Ribossômico/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , MéxicoRESUMO
To determine the role of rotavirus, enterotoxigenic Escherichia coli and enteropathogenic E. coli in diarrheal disease of non-hospitalized children and adults living in rural El Salvador, stool specimens were collected from 156 persons with diarrhea and 134 age- and sex-matched controls over a 1-year period. Enterotoxigenic Escherichia coli (ETEC) were isolated as frequently from controls (13.4%) as from diarrhea cases (12.2%). Enteropathogenic E. coli were isolated from 13 cases (8.3%) and 10 (7.7%) controls. Rotavirus was demonstrated in only five of the 129 specimens from cases examined; the five persons infected were less than or equal to 3 years of age. No invasive E. coli were found. Serotyping of ETEC revealed serogroups of ETEC previously associated with enterotoxigenicity but was not helpful in separating infection from disease. The etiology of diarrhea in this rural, non-hospitalized population was complex. Isolation of a known pathogen did not prove etiology. The rotaviruses, which have been isolated frequently from hospitalized persons, were rare. Further laboratory and epidemiologic studies in such populations are needed to identify those factors that determine pathogenicity.
Assuntos
Diarreia/microbiologia , Enterotoxinas/análise , Infecções por Escherichia coli/microbiologia , Viroses/microbiologia , Adolescente , Criança , Pré-Escolar , Diarreia Infantil/microbiologia , El Salvador , Escherichia coli/patogenicidade , Humanos , Lactente , Rotavirus/patogenicidade , População Rural , VirulênciaAssuntos
Infecções por Rickettsia/epidemiologia , Costa Rica , Surtos de Doenças , Feminino , Humanos , MasculinoRESUMO
A retrospective hospital chart review of meningococcal meningitis cases in Costa Rica revealed a large number of cases confirmed in the laboratory by Gram-stained smear and/or culture of spinal fluid. A large percentage of the isolates studied were serogroup C and all of these were sulfonamide resistant. The age-specific attack rates were high in the preschool children with the highest attack rate in children 3 to 5 months of age. Case fatality ratios were 14% overall, with the low fatality rates in individuals 10 to 29 years of age. The outbreak of serogroup C meningitis in 1970--1971 was relatively brief, country-wide, and not predominantly a urban outbreak. The few secondary cases observed occurred within the first 2 weeks of the primary case.
Assuntos
Meningite Meningocócica/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Costa Rica , Feminino , Humanos , Lactente , Masculino , Meningite Meningocócica/mortalidade , Pessoa de Meia-IdadeRESUMO
To test the hypothesis that the Duffy blood group negative genotype is a factor in resistance to Plasmodium vivax, we determined the Duffy blood group, the malaria antibodies, and the slide-demonstrated infection rates with P. vivax and P. falciparum of 420 persons living in Nueva Armenia, Honduras. In all, 247 persons were Duffy negative. Demonstrated infections with P. falciparum were almost equally distributed between Duffy-positive (5,8%) and Duffy-negative (4.9%) persons. Similarly, Duffy-positive (25.6%) and Duffy-negative (28.2%) persons had equal proportions of indirect fluorescent antibody test titers suggestive of past or present P. falciparum infection. In contrast, all 14 P. vivax infections were found in Duffy-negative persons. There was no evidence suggesting that Duffy-positive and Duffy-negative persons had different exposures to malaria. The Duffy negative genotype FyFy appears to be a factor in resistance to P. vivax.
Assuntos
Antígenos de Grupos Sanguíneos , Sistema do Grupo Sanguíneo Duffy , Imunidade Inata , Malária/imunologia , Anticorpos/análise , Sistema do Grupo Sanguíneo Duffy/genética , Honduras , Humanos , Malária/genética , Plasmodium falciparum/imunologia , Plasmodium vivax/imunologiaRESUMO
A focal outbreak of highly fatal disease occurred in eastern Costa Rica in 1974. No rickettsial spotted fevers have previously been reported in Costa Rica. Nevertheless, the available evidence points to an unidentified rickettsial pathogen, probably of the spotted fever group, as the agent responsible for this outbreak.
Assuntos
Infecções por Rickettsia/mortalidade , Adolescente , Anticorpos/análise , Antígenos/análise , Vetores Aracnídeos , Criança , Testes de Fixação de Complemento , Costa Rica , Surtos de Doenças , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Rickettsia/imunologia , Rickettsia rickettsii/imunologia , Rickettsia typhi/imunologia , Carrapatos/microbiologiaRESUMO
In the first 3 weeks after the 1976 earthquake in Guatemala a system for collecting, analysing, and disseminating information of medical importance was instituted in the disaster area. Data on cases of selected diseases, number of available hospital beds, and medical supplies were collected, and reported epidemics were investigated. The system functioned well despite the limited numbers of trained personnel. Collection and analysis were quick enough for data to be used immediately in decision-making. No epidemics of communicable diseases were observed in the affected area. The number of dog bites in Guatemala City increased but no cases of rabies were reported. The success of the surveillance system in Guatemala suggests that immediate use of epidemiological methods should be an integral part of disaster relief.