RESUMEN
Probiotics are used in the prophylaxis and treatment of several conditions, including irritable bowel syndrome, diarrhoea, necrotising enterocolitis (NEC) and colic in infants. Despite the long history of probiotic use in humans, there is still significant debate about their efficacy and safety, particularly in HIV-infected and immunocompromised individuals. Here, we reviewed the safety and adverse event (AE) reporting from clinical trials that have tested probiotics in at risk populations, including HIV-infected individuals, the terminally ill and elderly, and neonates. Our analysis suggests that the benefits of probiotic therapy outweigh their potential risks in HIV-infected populations, and in the treatment of colic and NEC in low birth weight or premature neonates. Most case reports of severe AEs were in the elderly and terminally ill, or in those with additional severe medical conditions. We conclude that probiotic use, as adjunctive treatment, is effective and safe in the majority of patients including HIV-infected individuals, although special care should be taken in individuals with extreme immunosuppression and severe medical conditions in all ages.
Asunto(s)
Infecciones por VIH/terapia , Huésped Inmunocomprometido/inmunología , Probióticos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Enterocolitis Necrotizante/terapia , Humanos , Recién Nacido , Enfermedades del Recién Nacido/terapia , Medición de Riesgo , Resultado del TratamientoRESUMEN
The population of the Indian subcontinent represents a very complex social and cultural structure. Occupying a geographically central position for the early modern human migrations, indications are that the founder group that migrated out of East Africa also reached India. In the present study we used the twin strategy of mapping the whole mitochondrial DNA (mtDNA) using the standard 14 restriction enzymes, and sequencing the non-transcribed HVSI region, to derive maximum maternal lineages from a sample of non-tribal Indians. The essential features of the reduced median network of the two datasets were the same. Both showed two demographic expansions of two major haplogroups, 'M' and 'N'. The reduced median network was drawn with inputs from other studies on the Indian population, and correlated with data from other ethnic populations. The coalescence time of expansions and genetic diversity were estimated. A reduced median network was also drawn combining data from studies on Africans, Southeast Asians and West-Eurasians, tracing the migration of 'M' from East Africa to India. A time estimate of the migration of major mtDNA haplogroups from Africa was attempted. The comparison of a set of Indian maternal lineages belonging to different geographical regions of the country, with other populations revealed the in-situ differentiation and antiquity of the Indian population. Our analysis places the 'southern route' migration as the source of haplogroup 'M'. Multiple migrations might have brought the other major haplogroups, 'N' and 'R', found in our sample to India. Archaeological evidence of modern humans in the subcontinent supports this mtDNA study.
Asunto(s)
ADN Mitocondrial/genética , Emigración e Inmigración , Evolución Molecular , Genética de Población , Haplotipos/genética , Análisis por Conglomerados , Cartilla de ADN , Humanos , India , Polimorfismo de Longitud del Fragmento de Restricción , Análisis de Secuencia de ADNRESUMEN
Recent studies on human mtDNA have identified continent-specific restriction enzyme sites and resultant haplo-groups among populations from different regions of the world. Such studies have helped in elaborating the models for human migrations. We have studied Indian mtDNAs to identify the recognized world ethnic elements present in it. The results presented here are based on the study of DdeI 10394 site along with the associated Asian-specific AluI 10397 site in the mtDNA sequences of the Indian samples. On examining all the related haplo-groups, this study suggests that the apparent affinities of Indians and East Asians (comprising Chinese, Japanese, Southeast Asians etc.) could be due to a proto-Asiatic element present in Indians.
Asunto(s)
Pueblo Asiatico/genética , ADN Mitocondrial/genética , Hominidae/genética , Filogenia , Población Blanca/genética , Animales , Asia Sudoriental , China , Etnicidad/genética , Haplotipos , Hominidae/clasificación , Humanos , India , Japón , Eliminación de SecuenciaRESUMEN
The hepatitis B virus X protein (pX) interacts directly with the bZip transactivator CREB and the bZip repressors ICERIIgamma and ATF3, increasing their DNA-binding affinity in vitro and their transcriptional efficacy in vivo. However, the mechanism of bZip-pX interaction and of the pX-mediated increase in the bZip transcriptional efficacy remains to be understood. In this study with deletion mutants of pX, we delineated a 67-amino-acid region spanning residues 49 to 115 required for direct CREB, ATF3, and ICER IIgamma interaction in vitro and in vivo and increased bZip/CRE binding in vitro. Transient transfections of the pX deletion mutants in AML12 hepatocytes demonstrate that pX(49-115) is as effective as the full-length pX in enhancing the ATF3- and ICERIIgamma-mediated transrepression. However, this pX region is inactive in increasing the transactivation efficacy of CREB; additional amino acid residues present in pX(49-140) are required to mediate the increased transactivation efficacy of CREB in vivo. This requirement for different regions of pX in affecting CREB transactivation suggests that amino acid residues 115 to 140 integrate additional events in effecting pX-mediated transactivation, such as concomitant interactions with select components of the basal transcriptional apparatus.
Asunto(s)
Proteínas de Unión al ADN/fisiología , Proteínas Represoras/genética , Transactivadores/genética , Factores de Transcripción/fisiología , Activación Transcripcional/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Línea Celular , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Factores de Unión a la G-Box , Hígado/citología , Hígado/metabolismo , Mutación , Eliminación de Secuencia , Activación Transcripcional/fisiología , Proteínas Reguladoras y Accesorias ViralesRESUMEN
The hepatitis B virus (HBV) encodes a 16.5 kDa multifunctional protein termed pX or HBx, required for transcription of the viral genome and implicated in the development of hepatocellular carcinoma (HCC) in chronic HBV-infected patients. However, the mechanism of pX-mediated hepatocarcinogenesis remains unknown. pX is a multifunctional protein exhibiting a number of activities affecting transcription, cell growth, and apoptotic cell death. Although pX does not directly bind DNA, pX is regarded as a promiscuous transactivator, acting via a dual mechanism: in the cytoplasm, pX activates mitogenic signaling cascades; in the nucleus, pX interacts directly with members of the bZip class of transcription factors and with specific components of the basal transcriptional apparatus. The focus of this review is to describe the transactivation function of pX and its role in hepatocarcinogenesis.
Asunto(s)
Carcinoma Hepatocelular/fisiopatología , Neoplasias Hepáticas/fisiopatología , Transactivadores/fisiología , Transcripción Genética , Animales , Metabolismo Basal , Carcinoma Hepatocelular/genética , Genoma Viral , Humanos , Leucina Zippers , Neoplasias Hepáticas/genética , Transducción de Señal/fisiología , Proteínas Reguladoras y Accesorias ViralesRESUMEN
The hepatitis B virus X protein interacts with the basic-region, leucine zipper protein (bZip) domain of cAMP response element-binding protein increasing its affinity for the cAMP response element site in vitro and its transcriptional efficacy in vivo (Williams, J. S., and Andrisani, O. M. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 3819-3823). Here we examine pX interactions with bZip transcription factors ATF3, gadd153/Chop10, ICER IIgamma, and NF-IL6. We demonstrate direct interactions in vitro between pX and the bZip proteins tested. In contrast MyoD and Gal4(1-147) fail to interact with pX. We also demonstrate by the mammalian two-hybrid assay the direct interaction of pX with cAMP response element- binding protein, ICER IIgamma, ATF3, and NF-IL6 in hepatocytes. In addition, pX increases the DNA binding potential of bZip proteins for their cognate DNA-binding site in vitro. In transient transfections in hepatocytes (AML12 cell line), pX increases the transcriptional efficacy of the bZip transcription factors. NF-IL6-mediated transcriptional activation is enhanced 3-fold by pX. Most interestingly, pX augments the repression mediated by bZip repressors ATF3 and ICER IIgamma, by 6- and 7-fold, respectively, demonstrating for the first time the involvement of pX in gene repression. We conclude that pX is an enhancer of the DNA binding potential of bZip transcription factors, thereby increasing the transactivation or repression efficacy of bZip-responsive genes.
Asunto(s)
Proteínas de Unión al ADN/fisiología , ADN/metabolismo , Leucina Zippers , Proteínas Represoras/fisiología , Transactivadores/fisiología , Factores de Transcripción/fisiología , Transcripción Genética , Animales , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Factores de Unión a la G-Box , Proteínas Reguladoras y Accesorias ViralesRESUMEN
Mitochondrial DNA variation was studied in 100 Indians using the same set of six restriction enzymes used in the study of other world ethnic groups in order to compare and discern possible relationships of the Indian populations. Twenty nine mtDNA types were found including the ones from an earlier study (Semino et al. 1991) and unweighted pair-group method (UPGMA) and maximum parsimony trees were constructed using the mtDNA types. The nucleotide diversity values were calculated using the maximum likelihood method. From a study of the shared mitochondrial DNA types and the parsimony tree (Fig. 2) we came to the conclusion that the Indian population is closer to Caucasians and has an admixture with Asians. The North Indian population appears to have a recent admixture of the Caucasian mtDNA types which is absent in the south.
Asunto(s)
ADN Mitocondrial/genética , Filogenia , Polimorfismo Genético , Población Blanca/genética , ADN Mitocondrial/clasificación , Frecuencia de los Genes , Geografía , Humanos , India/etnología , Funciones de Verosimilitud , Análisis por ApareamientoRESUMEN
To test the validity of the maximum parsimony approach to discern protistan interrelationships, we have derived an optimal network of 16S-like rRNA sequences using our parsimony algorithm and compared it with those reported using the distance matrix method. We have also derived an optimal network topology of 50 5S rRNA sequences through an interactive search using our algorithm. In both these networks, the kinetoplastids and euglenoids form a linkage group with Dictyostelium emerging from its neighbourhood. The cryptophytes, dinoflagellates and chromophytes and green algae emerge as independent lines suggesting that plastids arose more than once during protistan evolution. The large 5S rRNA tree further indicates independent origins of mesozoa and metazoa; kinetoplastids and ciliates; and diphyletic origin of fungi. Comparatively close positions of charales and land plants, chytrids and Zygomycetes, Physarum and amoeba, and red algae and green algae are also seen in this network.