RESUMO
BACKGROUND: Recurrent fetal loss (RFL) is a prevalent problem affecting approximately 1% of all women of childbearing age. Many factors can lead to RFL; however, recent studies have indicated the important role of the maternal immune system in this process. The human leukocyte antigens (HLA), HLA-linked genes and regulatory factors play an important role in fetal loss and in fetal development. The current retrospective study was preformed to examine the HLA alleles shared between couples with RFL in Saudi Arabia, using a large cohort of women (having three or more RFL). Specific HLA alleles that could influence this condition, or the number of miscarriages experienced, were expected to be highlighted in this way. METHODS: A total of 253 consecutive patients who visited the RFL clinic at the King AbdulAziz Medical City, National Guard Hospital in Riyadh were included in this study. They included 54 consanguineous couples, 132 non-consanguineous couples and another 67 couples shared only their tribal origin. Clinical examinations as well as laboratory investigations were carried out on each patient. Class I HLA, HLA-A, HLA-B and HLA-C, and Class II HLA, HLA-DR and HLA-DQ, were typed for each patient and their partner. RESULTS: No relationship was seen between sharing of HLA alleles and the number of RFL experienced by the couples, among neither consanguineous nor non-consanguineous couples. CONCLUSIONS: Although the results of this study suggest that HLA sharing is not an indicative factor in RFL, definitive conclusions on this topic must be based on large case-control studies.
Assuntos
Aborto Habitual/genética , Antígenos HLA/genética , Aborto Habitual/epidemiologia , Aborto Habitual/imunologia , Alelos , Consanguinidade , Feminino , Predisposição Genética para Doença , Antígenos HLA/imunologia , Humanos , Masculino , Estudos Retrospectivos , Arábia Saudita/epidemiologiaRESUMO
The structural maintenance of chromosomes (SMC) protein encoded by the fission yeast rad18 gene is involved in several DNA repair processes and has an essential function in DNA replication and mitotic control. It has a heterodimeric partner SMC protein, Spr18, with which it forms the core of a multiprotein complex. We have now isolated the human orthologues of rad18 and spr18 and designated them hSMC6 and hSMC5. Both proteins are about 1100 amino acids in length and are 27-28% identical to their fission yeast orthologues, with much greater identity within their N- and C-terminal globular domains. The hSMC6 and hSMC5 proteins interact to form a tight complex analogous to the yeast Rad18/Spr18 heterodimer. In proliferating human cells the proteins are bound to both chromatin and the nucleoskeleton. In addition, we have detected a phosphorylated form of hSMC6 that localizes to interchromatin granule clusters. Both the total level of hSMC6 and its phosphorylated form remain constant through the cell cycle. Both hSMC5 and hSMC6 proteins are expressed at extremely high levels in the testis and associate with the sex chromosomes in the late stages of meiotic prophase, suggesting a possible role for these proteins in meiosis.
Assuntos
Proteínas de Ciclo Celular/química , Proteínas Cromossômicas não Histona/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas Fúngicas/química , Proteínas de Saccharomyces cerevisiae , Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces/química , Sequência de Aminoácidos , Animais , Northern Blotting , Western Blotting , Proteínas de Ciclo Celular/metabolismo , Divisão Celular , Linhagem Celular , Linhagem Celular Transformada , Núcleo Celular/metabolismo , Células Cultivadas , Cromatina/metabolismo , Proteínas Cromossômicas não Histona/química , Clonagem Molecular , DNA Complementar/metabolismo , Proteínas de Ligação a DNA/química , Dimerização , Fibroblastos/metabolismo , Humanos , Meiose , Camundongos , Microscopia de Fluorescência , Dados de Sequência Molecular , Monoéster Fosfórico Hidrolases/metabolismo , Fosforilação , Ligação Proteica , Estrutura Terciária de Proteína , Homologia de Sequência de Aminoácidos , Distribuição Tecidual , Ubiquitina-Proteína LigasesRESUMO
Weak organic acid food preservatives exert pronounced culture pH-dependent effects on both the heat-shock response and the thermotolerance of Saccharomyces cerevisiae. In low-pH cultures, they inhibit this stress response and cause strong induction of respiratory-deficient petites amongst the survivors of lethal heat treatment. In higher pH cultures, 25 degrees C sorbic acid treatment causes a strong induction of thermotolerance without inducing the heat-shock response. In this study we show that trehalose, a major stress protectant, accumulates rapidly in S. cerevisiae exposed to sorbate at low pH. In pH 3.5 cultures, a 25 degrees C sorbate treatment is as effective as a 39 degrees C heat shock in inducing trehalose. This weak-acid-induced trehalose accumulation is enhanced in the pfk1 S. cerevisiae mutant, indicating that it arises through inhibition of glycolysis at the phosphofructokinase step. The more preservative-resistant food spoilage yeast Zygosaccharomyces bailii differs from S. cerevisiae in that: (1) its basal thermotolerance is not strongly affected by culture pH; (2) it does not display trehalose accumulation in response to 25 degrees C sorbate treatment at low pH; and (3) there is no induction of respiratory-deficient petites during lethal heating with sorbate. This probably reflects Z. bailii being both petite-negative and better equipped for maintenance of homeostasis during weak-acid, pH or high-temperature stress.
