RESUMEN
This clinical report describes the multidisciplinary treatment of a 16-year-old girl diagnosed with cemento-ossifying fibroma in the mandible. The resection of the lesion and reconstruction with a free osseous fibula flap with microvascular anastomosis was performed. Four months later, interpositional bone grafting of iliac spongy bone was used to gain bone height at the treated site. Twenty-four months later, 5 dental implants were placed. After a 6-month osseointegration period, a partial screw-retained fixed dental prosthesis was fabricated. Prosthodontic planning and treatment considerations are discussed.
Asunto(s)
Injerto de Hueso Alveolar , Implantación Dental Endoósea , Prótesis Dental de Soporte Implantado , Dentadura Parcial Fija , Fibroma Osificante/rehabilitación , Mandíbula/cirugía , Neoplasias Mandibulares/rehabilitación , Adolescente , Placas Óseas , Femenino , Fibroma Osificante/cirugía , Humanos , Neoplasias Mandibulares/cirugía , Colgajos QuirúrgicosRESUMEN
The brain serotonergic system has an essential role in the physiological functions of the central nervous system and dysregulation of serotonin (5-HT) homeostasis has been implicated in many neuropsychiatric disorders. The tryptophan hydroxylase-2 (TPH2) gene is the rate-limiting enzyme in brain 5-HT synthesis, and thus is an ideal candidate gene for understanding the role of dysregulation of brain serotonergic homeostasis. Here, we characterized a common, but functional single-nucleotide polymorphism (SNP rs1386493) in the TPH2 gene, which decreases efficiency of normal RNA splicing, resulting in a truncated TPH2 protein (TPH2-TR) by alternative splicing. TPH2-TR, which lacks TPH2 enzyme activity, dominant-negatively affects full-length TPH2 function, causing reduced 5-HT production. The predicted mRNA for TPH2-TR is present in postmortem brain of rs1386493 carriers. The rs13864923 variant does not appear to be overrepresented in either global or multiplex depression cohorts. However, in combination with other gene variants linked to 5-HT homeostasis, this variant may exhibit important epistatic influences.
Asunto(s)
Empalme Alternativo , Depresión/genética , Predisposición Genética a la Enfermedad/genética , Serotonina/biosíntesis , Triptófano Hidroxilasa/genética , Animales , Tronco Encefálico/metabolismo , Línea Celular Transformada , Femenino , Predisposición Genética a la Enfermedad/psicología , Genotipo , Humanos , Masculino , Células PC12 , Linaje , Polimorfismo de Nucleótido Simple/genética , RatasRESUMEN
Visualization of nuclear architecture is key to the understanding of the association between RNA synthesis and processing. This architecture is obscured by the high density of components in most nuclei. We have developed a method of spreading nuclei and nucleoli that reduces overlap of weakly associated components. Strong interactions among nuclear components are not disrupted by this method. Spread nucleoli remained structurally distinct and functionally competent in ribosomal RNA synthesis. Nascent ribosomal RNA colocalized with RNA polymerase I and fibrillarin, a protein required for processing of ribosomal RNA. Colocalization of nascent transcripts and fibrillarin was seen in nucleoli spread over several microns, suggesting a strong interaction. These data suggest that nucleoli are superassemblies of bipartite domains, each composed of a ribosomal RNA synthesis center tightly associated with areas likely to be involved in ribosomal RNA processing.
Asunto(s)
Núcleo Celular/ultraestructura , ADN Ribosómico/biosíntesis , Animales , Anticuerpos Monoclonales , Western Blotting , Línea Celular , Nucléolo Celular/metabolismo , Nucléolo Celular/ultraestructura , Núcleo Celular/metabolismo , Chlorocebus aethiops , Proteínas Cromosómicas no Histona/análisis , ADN Ribosómico/análisis , Humanos , Sueros Inmunes , Riñón , Ratones , Microscopía Fluorescente , Ribonucleoproteínas/análisis , Ribonucleoproteínas Nucleares Pequeñas/análisis , Transcripción GenéticaRESUMEN
Several human viruses are able to latently infect specific target cell populations in vivo. Analysis of the replication cycles of herpes simplex virus, Epstein-Barr virus, and human immunodeficiency virus suggests that the latent infections established by these human pathogens primarily result from a lack of host factors critical for the expression of viral early gene products. The subsequent activation of specific cellular transcription factors in response to extracellular stimuli can induce the expression of these viral regulatory proteins and lead to a burst of lytic viral replication. Latency in these eukaryotic viruses therefore contrasts with latency in bacteriophage, which is maintained primarily by the expression of virally encoded repressors of lytic replication.
Asunto(s)
Fenómenos Fisiológicos de los Virus , VIH-1/patogenicidad , VIH-1/fisiología , Herpesvirus Humano 4/patogenicidad , Herpesvirus Humano 4/fisiología , Humanos , Modelos Biológicos , Simplexvirus/patogenicidad , Simplexvirus/fisiología , Virus/patogenicidadRESUMEN
OBJECTIVES: To measure the plasma levels of total homocysteine (tHcy) in children with type I diabetes mellitus and their relationship with the control of the disease. MATERIAL AND METHODS: We studied a total of 46 patients with ages between 4 and 19 years. The analyzed variables were: sex, age, puberty stage by Tanner, BMI, years of evolution of the illness, self-monitoring, associated diseases, tHcy, folic acid, vitamin B12, glycosylated haemoglobin (HbA1c), lipid profile and renal function. RESULTS: The mean tHcy was of 5.48 +/- 1,64 microm/l, similar to that in our control population. There was a positive correlation with tHcy when analyzing the puberty stage by the Tanner scale. The years of evolution of diabetes varied between 0.4 and 15, with a mean of 5.77 +/- 3.69, with no correlation with tHcy. The glycosylated haemoglobin mean was 7.35 %, with no correlation with tHcy. The levels of folic acid and vitamin B12 were similar to the control population. The lipid profile of our patients was normal, with no association with tHcy levels. There was no correlation between GFR and tHcy. CONCLUSIONS: A clinically correct control of children with diabetes mellitus type 1, appears to ensure a normal total homocysteinemia, with no significant differences with the healthy individuals of the same age and social environment.
Asunto(s)
Diabetes Mellitus Tipo 1/sangre , Homocisteína/sangre , Adolescente , Niño , Femenino , Humanos , MasculinoRESUMEN
Tat protein strongly activates transcription from the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) by enhancing the elongation efficiency of RNA polymerase II complexes. Tat-mediated transcriptional activation requires cellular cofactors and specific cis-acting elements within the HIV-1 promoter, among them a functional TATA box. Here, we have investigated the mechanism by which one of these cofactors, termed CA150, regulates HIV-1 transcription in vivo. We present a series of functional assays that demonstrate that the regulation of the HIV-1 LTR by CA150 has the same functional requirements as the activation by Tat. We found that CA150 affects elongation of transcription complexes assembled on the HIV-1 promoter in a TATA-box-dependent manner. We discuss the data in terms of the involvement of CA150 in the regulation of Tat-activated HIV-1 gene expression. In addition, we also provide evidence suggesting a role for CA150 in the regulation of cellular transcriptional processes.
Asunto(s)
Regulación Viral de la Expresión Génica , Duplicado del Terminal Largo de VIH , VIH-1/genética , ARN Polimerasa II/metabolismo , TATA Box , Transactivadores/metabolismo , Línea Celular Transformada , Proteínas de Unión al ADN/genética , Productos del Gen tat/metabolismo , Humanos , Regiones Promotoras Genéticas , Proteína de Unión a TATA-Box , Transactivadores/genética , Factores de Transcripción/genética , Transcripción Genética , Factores de Elongación Transcripcional , Productos del Gen tat del Virus de la Inmunodeficiencia HumanaRESUMEN
A mammalian splicing commitment complex was functionally defined by using a template commitment assay. This complex was partially purified and shown to be a required intermediate for complex A formation. The productive formation of this commitment complex required both splice sites and the polypyrimidine tract. U1 small nuclear ribonucleoprotein (snRNP) was the only spliceosomal U snRNP required for this formation. A protein factor, very likely U2AF, is probably involved in the formation of the splicing commitment complex. From the kinetics of appearance of complex A and complex B, it was previously postulated that complex A represents a functional intermediate in spliceosome assembly. Complex A was partially purified and shown to be a required intermediate for complex B (spliceosome) formation. Thus, a spliceosome pathway is for the first time supported by direct biochemical evidence: RNA+U1 snRNP+?U2 auxiliary factor+?Y----CC+U2 snRNP+Z----A+U4/6,5 snRNPs+ beta----B.
Asunto(s)
Empalme del ARN , Ribonucleoproteínas Nucleares Pequeñas/metabolismo , Secuencia de Bases , Núcleo Celular/metabolismo , Centrifugación por Gradiente de Densidad , ADN , Células HeLa , Humanos , Intrones , Datos de Secuencia Molecular , Proteínas Nucleares/metabolismo , ARNRESUMEN
Alternative splicing of fibroblast growth factor receptor 2 (FGF-R2) transcripts involves the mutually exclusive usage of exons IIIb and IIIc to produce two different receptor isoforms. Appropriate splicing of exon IIIb in rat prostate cancer DT3 cells requires a previously described cis element (ISAR, for "intronic splicing activator and repressor") which represses the splicing of exon IIIc and activates the splicing of exon IIIb. This element is nonfunctional in rat prostate AT3 cells, which repress exon IIIb inclusion and splice to exon IIIc. We have now identified an intronic element upstream of exon IIIb that causes repression of exon IIIb splicing. Deletion of this element abrogates the requirement for ISAR in order for exon IIIb to be spliced in DT3 cells and causes inappropriate inclusion of exon IIIb in AT3 cells. This element consists of two intronic splicing silencer (ISS) sequences, ISS1 and ISS2. The ISS1 sequence is pyrimidine rich, and in vitro cross-linking studies demonstrate binding of polypyrimidine tract binding protein (PTB) to this element. Competition studies demonstrate that mutations within ISS1 that abolish PTB binding in vitro alleviate splicing repression in vivo. Cotransfection of a PTB-1 expression vector with a minigene containing exon IIIb and the intronic splicing silencer element demonstrate PTB-mediated repression of exon IIIb splicing. Furthermore, all described PTB isoforms were equally capable of mediating this effect. Our results support a model of splicing regulation in which exon IIIc splicing does not represent a default splicing pathway but rather one in which active repression of exon IIIb splicing occurs in both cells and in which DT3 cells are able to overcome this repression in order to splice exon IIIb.
Asunto(s)
Empalme Alternativo/genética , Proteínas de Unión al ADN/fisiología , Exones/genética , Silenciador del Gen , Intrones/genética , Proteínas de Unión al ARN/fisiología , Proteínas Tirosina Quinasas Receptoras/genética , Receptores de Factores de Crecimiento de Fibroblastos/genética , Adenocarcinoma/genética , Adenocarcinoma/patología , Animales , Regulación Neoplásica de la Expresión Génica , Masculino , Mutagénesis Sitio-Dirigida , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/genética , Reacción en Cadena de la Polimerasa , Proteína de Unión al Tracto de Polipirimidina , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Precursores del ARN/metabolismo , ARN Neoplásico/metabolismo , Ratas , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/fisiología , Secuencias Reguladoras de Ácidos Nucleicos , Eliminación de Secuencia , Células Tumorales CultivadasRESUMEN
Alternative splicing of fibroblast growth factor receptor 2 (FGF-R2) is an example of highly regulated alternative splicing in which exons IIIb and IIIc are utilized in a mutually exclusive manner in different cell types. The importance of this splicing choice is highlighted by studies which indicate that deregulation of the FGF-R2 splicing is associated with progression of prostate cancer. Loss of expression of a IIIb exon-containing isoform of FGF-R2 [FGF-R2 (IIIb)] accompanies the transition of a well-differentiated, androgen-dependent rat prostate cancer cell line, DT3, to the more aggressive, androgen-independent AT3 cell line. We have used transfection of rat FGF-R2 minigenes into DT3 and AT3 cancer cell lines to study the mechanisms that control alternative splicing of rat FGF-R2. Our results support a model in which an important cis-acting element located in the intron between these alternative exons mediates activation of splicing using the upstream IIIb exon and repression of the downstream IIIc exon in DT3 cells. This element consists of 57 nucleotides (nt) beginning 917 nt downstream of the IIIb exon. Analysis of mutants further demonstrates that an 18-nt "core sequence" within this element is most crucial for its function. Based on our observations, we have termed this sequence element ISAR (for intronic splicing activator and repressor), and we suggest that factors which bind this sequence are required for maintenance of expression of the FGF-R2 (IIIb) isoform.
Asunto(s)
Empalme Alternativo , Intrones , Precursores del ARN/metabolismo , Empalme del ARN , Proteínas Tirosina Quinasas Receptoras/genética , Receptores de Factores de Crecimiento de Fibroblastos/genética , Secuencias Reguladoras de Ácidos Nucleicos , Animales , Secuencia de Bases , Desoxirribonucleasas de Localización Especificada Tipo II/metabolismo , Exones , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Humanos , Datos de Secuencia Molecular , Ratas , Proteínas Tirosina Quinasas Receptoras/metabolismo , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Eliminación de Secuencia , Homología de Secuencia de Ácido Nucleico , Células Tumorales CultivadasRESUMEN
CA150 represses RNA polymerase II (RNAPII) transcription by inhibiting the elongation of transcripts. The FF repeat domains of CA150 bind directly to the phosphorylated carboxyl-terminal domain of the largest subunit of RNAPII. We determined that this interaction is required for efficient CA150-mediated repression of transcription from the alpha(4)-integrin promoter. Additional functional determinants, namely, the WW1 and WW2 domains of CA150, were also required for efficient repression. A protein that interacted directly with CA150 WW1 and WW2 was identified as the splicing-transcription factor SF1. Previous studies have demonstrated a role for SF1 in transcription repression, and we found that binding of the CA150 WW1 and WW2 domains to SF1 correlated exactly with the functional contribution of these domains for repression. The binding specificity of the CA150 WW domains was found to be unique in comparison to known classes of WW domains. Furthermore, the CA150 binding site, within the carboxyl-terminal half of SF1, contains a novel type of proline-rich motif that may be recognized by the CA150 WW1 and WW2 domains. These results support a model for the recruitment of CA150 to repress transcription elongation. In this model, CA150 binds to the phosphorylated CTD of elongating RNAPII and SF1 targets the nascent transcript.
Asunto(s)
Proteínas de Unión al ADN , ARN Polimerasa II/metabolismo , Precursores del ARN/metabolismo , Empalme del ARN , Proteínas de Unión al ARN/metabolismo , Proteínas Represoras/metabolismo , Transactivadores/metabolismo , Factores de Transcripción , Secuencia de Aminoácidos , Sitios de Unión , Línea Celular Transformada , Regulación de la Expresión Génica , Células HeLa , Humanos , Datos de Secuencia Molecular , Fosforilación , Prolina/metabolismo , Factores de Empalme de ARN , Proteínas de Unión al ARN/genética , Proteínas Represoras/genética , Relación Estructura-Actividad , Transactivadores/genética , Factores de Elongación TranscripcionalRESUMEN
Maximal human immunodeficiency virus type 1 (HIV-1) gene expression requires specific cellular factors in addition to the virus-encoded trans-activator protein Tat and the RNA element TAR. We developed a functional assay, based on transcriptional activation in vitro, to identify these cellular factors. Here, we describe the purification and molecular cloning of CA150, a nuclear protein that is associated with the human RNA polymerase II holoenzyme and is involved in Tat-dependent HIV-1 transcriptional activation. The sequence of CA150 contains an extensive glutamine- and alanine-rich repeat that is found in transcriptional modulators such as GAL11 and SSN6 in Saccharomyces cerevisiae and Zeste in Drosophila melanogaster. Immunodepletion of CA150 abolished Tat trans activation in vitro. Moreover, overexpression of a mutant CA150 protein specifically and dramatically decreased Tat-mediated activation of the HIV-1 promoter in vivo, strongly suggesting a role for CA150 in HIV-1 gene regulation. Immunoprecipitation experiments demonstrated that both CA150 and Tat associate with the RNA polymerase II holoenzyme. Furthermore, we found that functional Tat associates with the holoenzyme whereas activation-deficient Tat mutants do not. Thus, we propose that Tat action is transduced via an RNA polymerase II holoenzyme that contains CA150.
Asunto(s)
VIH-1/genética , Proteínas Nucleares/metabolismo , ARN Polimerasa II/metabolismo , Transactivadores/metabolismo , Activación Transcripcional/fisiología , Alanina , Secuencia de Aminoácidos , Extractos Celulares , Núcleo Celular/química , Clonación Molecular , Coenzimas/metabolismo , Regulación Viral de la Expresión Génica/fisiología , Productos del Gen tat/fisiología , Glutamina , Células HeLa , Humanos , Datos de Secuencia Molecular , Mutación , Proteínas Nucleares/análisis , Proteínas Nucleares/genética , Proteínas Nucleares/aislamiento & purificación , Regiones Promotoras Genéticas/genética , Análisis de Secuencia de ADN , Transactivadores/análisis , Transactivadores/genética , Transactivadores/aislamiento & purificación , Factores de Elongación Transcripcional , Productos del Gen tat del Virus de la Inmunodeficiencia HumanaRESUMEN
Sxl has been proposed to regulate splicing of specific target genes by directly interacting with their pre-mRNAs. We have therefore examined the RNA-binding properties of Sxl protein in vitro and in vivo. Gel shift and UV cross-linking assays with a purified recombinant MBP-Sxl fusion protein demonstrated preferential binding to RNAs containing poly(U) tracts, and the protein footprinted over the poly(U) region. The protein did not appear to recognize either branch point or AG dinucleotide sequences, but an adenosine residue at the 5' end of the poly(U) tract enhanced binding severalfold. MBP-Sxl formed two shifted complexes on a tra regulated acceptor site RNA; the doubly shifted form may have been stabilized by protein-protein interactions. Consistent with its proposed role in pre-mRNA processing, in nuclear extracts Sxl was found in large ribonucleoprotein (RNP) complexes which sedimented significantly faster than bulk heterogeneous nuclear RNP and small nuclear RNPs. Anti-Sxl staining of polytene chromosomes showed Sxl protein at a number of chromosomal locations, among which was the Sxl locus itself. Sxl protein could also be targeted to a new chromosomal site carrying a transgene containing splicing regulatory sequences from the Sxl gene, following transcriptional induction. After prolonged heat shock, all Sxl protein was restricted to the heat-induced puff at the hs93D locus. In contrast, a presumptive small nuclear RNP protein was observed at several heat puffs following shock.
Asunto(s)
Proteínas de Drosophila , Drosophila melanogaster/metabolismo , Hormonas de Insectos/metabolismo , Precursores del ARN/metabolismo , Procesamiento Postranscripcional del ARN , Proteínas de Unión al ARN/metabolismo , ARN/metabolismo , Animales , Secuencia de Bases , Sitios de Unión , Unión Competitiva , Línea Celular , Núcleo Celular/metabolismo , Cromosomas/metabolismo , Cromosomas/ultraestructura , Drosophila melanogaster/genética , Ribonucleoproteínas Nucleares Heterogéneas , Hormonas de Insectos/biosíntesis , Cinética , Datos de Secuencia Molecular , Oligorribonucleótidos/metabolismo , Oligorribonucleótidos/farmacología , ARN/biosíntesis , Empalme del ARN , Proteínas Recombinantes de Fusión/metabolismo , Ribonucleoproteínas/metabolismo , Ribonucleoproteínas Nucleares Pequeñas/metabolismoRESUMEN
In murine BALB/c 3T3 cell cultures, either beta interferon or platelet-derived growth factor (PDGF) enhanced expression of the 2',5'-oligoadenylate synthetase mRNA and protein. The time course of induction in response to beta interferon was similar to that in response to PDGF. Of several growth factors known to be present in clotted blood serum (i.e., epidermal growth factor, transforming growth factor beta, and PDGF), only PDGF enhanced expression of 2',5'-oligoadenylate synthetase. The linkage of an interferon response element-containing segment from the 5'-flanking region of a human or murine 2',-5'-oligoadenylate synthetase gene made a heterologous gene responsive to interferon. The expression of such a gene construct in transfected cells was also induced by PDGF. Induction by PDGF was inhibited by mono- or polyclonal antibodies to murine interferon, which suggested that induction by PDGF requires interferon. Both PDGF and interferon induced nuclear factors that bound to this interferon response element-containing segment in vitro.
Asunto(s)
2',5'-Oligoadenilato Sintetasa/genética , Interferón Tipo I/farmacología , Factor de Crecimiento Derivado de Plaquetas/farmacología , 2',5'-Oligoadenilato Sintetasa/biosíntesis , Animales , Células Clonales/efectos de los fármacos , Células Clonales/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Productos del Gen tat , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Factores de Transcripción/metabolismoRESUMEN
We have developed RNA molecules capable of effecting spliceosome-mediated RNA trans-splicing reactions with a target messenger RNA precursor (pre-mRNA). Targeted trans-splicing was demonstrated in a HeLa nuclear extract, cultured human cells, and H1299 human lung cancer tumors in athymic mice. Trans-splicing between a cancer-associated pre-mRNA encoding the beta-subunit of human chorionic gonadotropin gene 6 and pre-trans-splicing molecule (PTM) RNA was accurate both in vitro and in vivo. Comparison of targeted versus nontargeted trans-splicing revealed a moderate level of specificity, which was improved by the addition of an internal inverted repeat encompassing the PTM splice site. Competition between cis- and trans-splicing demonstrated that cis-splicing can be inhibited by trans-splicing. RNA repair in a splicing model of a nonfunctional lacZ transcript was effected in cells by a PTM, which restored significant beta-galactosidase activity. These observations suggest that spliceosome-mediated RNA trans-splicing may represent a general approach for reprogramming the sequence of targeted transcripts, providing a novel approach to gene therapy.
Asunto(s)
Ingeniería Genética , Terapia Genética , Empalme del ARN/fisiología , Empalmosomas/genética , Animales , Gonadotropina Coriónica Humana de Subunidad beta/genética , Cartilla de ADN , Exones , Globinas/genética , Células HeLa , Humanos , Ratones , Ratones Desnudos , Modelos Biológicos , Neoplasias Experimentales , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Análisis de Secuencia de ADN , Factores de Tiempo , Transfección , Células Tumorales Cultivadas , beta-Galactosidasa/metabolismoRESUMEN
The cascade that culminates in macrometastases is thought to be mediated by phenotypic plasticity, including epithelial-mesenchymal and mesenchymal-epithelial transitions (EMT and MET). Although there is substantial support for the role of EMT in driving cancer cell invasion and dissemination, much less is known about the importance of MET in the later steps of metastatic colonization. We created novel reporters, which integrate transcriptional and post-transcriptional regulation, to test whether MET is required for metastasis in multiple in vivo cancer models. In a model of carcinosarcoma, metastasis occurred via an MET-dependent pathway; however, in two prostate carcinoma models, metastatic colonization was MET independent. Our results provide evidence for both MET-dependent and MET-independent metastatic pathways.
Asunto(s)
Transición Epitelial-Mesenquimal , Metástasis de la Neoplasia , Animales , Proliferación Celular , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Neoplasias/patologíaRESUMEN
Progression of prostate cancer from an androgen sensitive to androgen insensitive tumor has previously been shown to be accompanied by a change in alternative splicing of fibroblast growth factor receptor 2 (FGF-R2) in a rat model of prostate cancer. This change results in loss of the FGF-R2(IIIb) isoform and predominant expression of the FGF-R2(IIIc) isoform. We sought to determine whether this change in FGF-R2 splicing is also associated with androgen insensitivity in human prostate tumors. We analysed three well characterized human prostate cancer cell lines and three metastatic prostate tumors which have been maintained as xenografts in nude mice. One of the cell lines, LNCaP, and two of the xenografts, DUKAP-1 and DUKAP-2, have been characterized as androgen sensitive, whereas two of the cell lines, DU-145 and PC-3, and one of the xenografts, DU9479, display androgen independent growth. Using an RT-PCR based assay, we demonstrated that progressive loss of the FGF-R2(111b) isoform correlated with androgen insensitivity in these human prostate cancer models. These findings lend support to the hypothesis that that loss of FGF-R2(IIIb) may be one step in a series of events which lead to progression of human prostate cancer.
Asunto(s)
Empalme Alternativo , Factores de Crecimiento de Fibroblastos , Neoplasias Hormono-Dependientes/genética , Neoplasias de la Próstata/genética , Proteínas Tirosina Quinasas Receptoras/genética , Proteínas Tirosina Quinasas Receptoras/metabolismo , Receptores de Factores de Crecimiento de Fibroblastos/genética , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Andrógenos/fisiología , Animales , Progresión de la Enfermedad , Factor 10 de Crecimiento de Fibroblastos , Factor 7 de Crecimiento de Fibroblastos , Sustancias de Crecimiento/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Hormono-Dependientes/metabolismo , Neoplasias de la Próstata/metabolismo , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos , Trasplante HeterólogoRESUMEN
La rehabilitación implanto-protética de maxilares con atrofia severa, presenta un desafío en la odontología actual. La falta de tejido óseo para la colocación de implantes estánda- res, conlleva tener que decidir una alternativa de tratamiento para el paciente. El objetivo de esta publicación es presentar dos casos clínicos del tratamiento de la atrofia de maxi- lar superior a través de implantes cigomáticos. Se presentan dos casos clínicos operados mediante la metodología descrita por Branemark, debatiendo las alternativas quirúrgicas actuales. Una paciente presentó dolor peri-orbitario, que fue resuelto inmediatamente. No se presentaron otras complicaciones post quirúrgicas. Se discuten alternativas pro- téticas de la resolución de estos casos. Transcurridos 12 y 18 meses de la rehabilitación implanto protética, no se presentaron otras complicaciones quirúrgicas ni protéticas en ambos pacientes. Se concluye que la rehabilitación con implantes cigomáticos es una alternativa válida para rehabilitar los maxilares superiores atróficos, de corto tiempo, baja morbilidad, y que presenta tasas de éxito similares a los implantes convencionales.
Implant-prosthetic rehabilitation of severe atrophic maxilla is a challenge for clinicians. Decision making when patients lack of bone density or quantity is usually difficult. The aim of this study is to report two cases of severe atrophic maxilla treated through zygo- matic implants. Two clinical reports using the Branemark methodology are presented, in which surgical alternatives are discussed. One patient had post-surgical pain in the peri orbital area and could be solved immediately. No other surgical complications were observed. Prosthetic alternatives are also discussed. After 12 and 18 months of functional loading, neither surgical nor prosthetic problems occurred. In conclusion, zygomatic implants are a viable, short time, low morbidity treatment in patients with an atrophic maxilla and present success rates similar to conventional implants.
RESUMEN
Nascent transcripts are the true substrates for many splicing events in mammalian cells. In this review we discuss transcription, splicing, and alternative splicing in the context of co-transcriptional processing of pre-mRNA. The realization that splicing occurs co-transcriptionally requires two important considerations: First, the cis-acting elements in the splicing substrate are synthesized at different times in a 5' to 3' direction. This dynamic view of the substrate implies that in a 100 kb intron the 5' splice site will be synthesized as much as an hour before the 3' splice site. Second, the transcription machinery and the splicing machinery, which are both complex and very large, are working in close proximity to each other. It is therefore likely that these two macromolecular machines interact, and recent data supporting this notion is discussed. We propose a model for co-transcriptional pre-mRNA processing that incorporates the concepts of splice site-tethering and dynamic exon definition. Also, we present a dynamic view of the alternative splicing of FGF-R2 and suggest that this view could be generally applicable to many regulated splicing events.
Asunto(s)
Empalme Alternativo , Precursores del ARN/genética , Transcripción Genética/genética , Animales , Humanos , Modelos Biológicos , ARN Polimerasa II/metabolismo , Precursores del ARN/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
We studied yellow fever virus infection in two species of monkey: Saimiri sciureus (squirrel monkeys) and Macaca mulatta (rhesus monkeys). Human gamma interferon was administered intravenously in five equal doses, one was given 24 hr before infection followed by four doses 24 hr apart. Interferon reduced the levels and duration of viremia and the severity of hepatitis in squirrel monkeys. Interferon prolonged survival time and delayed the appearance of viremia and hepatitis in infected rhesus monkeys, but it did not change overall mortality.
Asunto(s)
Interferón gamma/uso terapéutico , Viremia/terapia , Fiebre Amarilla/terapia , Alanina Transaminasa/sangre , Animales , Modelos Animales de Enfermedad , Femenino , Inyecciones Intravenosas , Interferón gamma/administración & dosificación , Macaca mulatta , Distribución Aleatoria , SaimiriRESUMEN
INTRODUCTION: Citrullinemia is an autosomal recessive disease, which is caused by a deficiency of the argininosuccinate synthetase. The neonatal forms are serious and many times are associated with a high level of mortality. CASE REPORT: A newborn that came in again on her third day of life due to a apneic episodes which required mechanical ventilation. Previously, she rejected feeding, had poor suction, lethargy and remarkable hypoactivity. During the following hours, she showed serious neurologycal deterioration with multifocal convulsions and coma, passing away 20 hours after admission due to endocraneal hypertension. The metabolic evaluation confirmed very significant hyperammonemia, with important increase of citrullin and glutamin, and arginine in the low limits of normality. She was treated with sodium benzoate and arginine and she also needed exanguinotransfusion. It was not possible to put her on hemodyalisis. The findings of the autopsy confirmed massive cerebral edema and characteristic hystological changes in the liver. The determination of the enzymatical activity in liver tissue showed a partial deficiency, with a residual activity of 25% of the average control. CONCLUSIONS: This is a case of fulminant neonatal citrullinemia that we considered of interest in order to draw the attention of the clinical on this type of diseases. The prognosis depends on early diagnosis, witch is based on clinical suspicion and analytical determination of ammonia in every newborn with unexplained vomiting, lethargy or other symptoms of encephalopathy.