RESUMO
OBJECTIVE: To use the technique of complementation analysis to help define genotype and classify patients with clinical manifestations consistent with those of the disorders of peroxisome assembly, namely the Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and rhizomelic chondrodysplasia punctata (RCDP). STUDY DESIGN: Clinical findings, peroxisomal function, and complementation groups were examined in 173 patients with the clinical manifestations of these disorders. RESULTS: In 37 patients (21%), peroxisome assembly was intact and isolated deficiencies of one of five peroxisomal enzymes involved in the beta-oxidation of fatty acids or plasmalogen biosynthesis were demonstrated. Ten complementation groups were identified among 93 patients (54%) with impaired peroxisome assembly and one of three phenotypes (ZS, NALD, or IRD) without correlation between complementation group and phenotype. Forty-three patients (25%) had impaired peroxisome assembly associated with the RCDP phenotype and belonged to a single complementation group. Of the 173 patients, 10 had unusually mild clinical manifestations, including survival to the fifth decade or deficits limited to congenital cataracts. CONCLUSIONS: At least 16 complementation groups, and hence genotypes, are associated with clinical manifestations of disorders of peroxisome assembly. The range of phenotype is wide, and some patients have mild involvement.
Assuntos
Adrenoleucodistrofia/genética , Microcorpos/genética , Fenótipo , Doença de Refsum/genética , Síndrome de Zellweger/genética , Aciltransferases/deficiência , Adrenoleucodistrofia/sangue , Adrenoleucodistrofia/enzimologia , Adulto , Células Cultivadas , Criança , Ácidos Graxos , Feminino , Teste de Complementação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Refsum/sangue , Doença de Refsum/enzimologia , Síndrome de Zellweger/sangue , Síndrome de Zellweger/enzimologiaRESUMO
This article considers the argument that the North American Free Trade Agreement (NAFTA) would encourage US and Canadian industry to relocate their hazardous manufacturing operations to Mexico. Proponents of this view believe that this industrial flight south would worsen working conditions in Mexico as well as lower occupational health and safety standards in the US and Canada. In evaluating this argument, the article examines working conditions in US-owned factories in the Mexican maquiladora zone, reviews the current occupational health and safety regulatory structure in Mexico, and considers those institutions established by the European Community to protect workers against the flight of hazardous industries. The article concludes that the harmonization of labor norms throughout North American and the establishment of a functional North American regulatory structure following the precedents set by the European Community are necessary steps to ensure that NAFTA does not produce the feared flight of hazardous industries to Mexico nor degrade the health of workers in Mexico, Canada, or the US.
Assuntos
Comércio , Cooperação Internacional , Saúde Ocupacional , Adolescente , Adulto , Poluentes Ocupacionais do Ar/toxicidade , Canadá , Poluição Ambiental/prevenção & controle , União Europeia , Feminino , Substâncias Perigosas , Resíduos Perigosos , Direitos Humanos , Humanos , Masculino , México , Doenças Profissionais/induzido quimicamente , Doenças Profissionais/etiologia , Doenças Profissionais/prevenção & controle , Exposição Ocupacional/legislação & jurisprudência , Saúde Ocupacional/legislação & jurisprudência , Estados Unidos , United States Occupational Safety and Health AdministrationRESUMO
In the testis of the neonatal rat, maturation of germ cells, or gonocytes, lays the foundations for spermatogenesis which will begin later in postnatal development. One of the most critical and yet least understood of the events that occur during the immediate neonatal period is relocation of gonocytes from the more central part of the seminiferous cord, where they are surrounded by Sertoli cells, to its periphery, where they contact the basement membrane. For the current study, we examined this change in gonocyte position by identifying some of the cellular mechanism involved, with the aim of determining whether movement of gonocytes to the basement membrane in vivo and development of cellular processes by these cells in vitro represents a resumption of migratory activity similar to that displayed by their fetal ancestors and by other motile cells. First, we used either thiamine pyrophosphatase cytochemistry or the fluorescent probe nitrobenzoxadiazole ceramide to visualize the Golgi complex in gonocytes and found that (1) this organelle matures and apparently enlarges in vivo with a time course paralleling movement of gonocytes to the basement membrane and undergoes similar changes in vitro that correlate with gonocyte process formation, and (2) the Golgi complex is located in perinuclear cytoplasm facing the apparent direction of gonocyte movement in vivo and in cytoplasm near the cellular process in the great majority of elongated gonocytes in coculture. Next we used two drugs, brefeldin A and monensin, which have in common their ability to disrupt the Golgi complex, and found that both drugs prevent process formation by gonocytes in a manner that is completely reversible. We also tested the involvement of the cytoskeleton in gonocyte elongation by utilizing nocodazole to disrupt and taxol to stabilize microtubules, as verified by alpha-tubulin immunofluorescence. Inclusion of the drug abolished (taxol) or substantially diminished (nocodazole) the ability of gonocytes to elongate in a reversible manner. We also found that the Golgi complex was intact in the presence of taxol and that microtubules were intact in the presence of both Golgi complex-specific drugs. Thus, our findings indicate that (1) both the Golgi complex and microtubules are involved in development of processes by gonocytes and (2) neither structure is sufficient by itself to allow these cells to elongate. Taken together, our data provide new evidence suggesting that the cellular mechanism utilized by postnatal gonocytes in relocating to the basement membrane are those mediating active migration.(ABSTRACT TRUNCATED AT 400 WORDS)