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Biomedical subjects

J M Izquierdo

Publications and source records attributed to J M Izquierdo.

At least 19 recordsLinked to original sources
PubMed2005

[Cervical myelopathy: retrospective analysis of surgical results in 53 cases treated by anterior cervical discectomy and interbody fusion].

PATIENTS AND METHODS: We perform a retrospective analysis of clinical results in 53 consecutive patients surgically treated for cervical myelopathy or myelo-radiculopathy with anterior cervical discectomy and interbody fusion by means of the Cloward procedure. RESULTS: 64.2% of the patients had good outcome as measured by the improvement in one or more grades in the Nurick's scale. No mortality related to the surgical procedure was noted, although 9.4% of the cases suffered neurological deterioration. Correct fusion was achieved in 92.5% of the patients, with a rate of post-surgical kyphosis of 9.4%. Multivariate analysis identified as factors related to the clinical outcome: age (p = 0.008), vascular risk factors (p = 0.031), duration of symptoms (p = 0.002), pre-surgical neurological status (p < 0.001), neuroradiological diagnosis (p = 0.014), intra-medullary high signal intensity changes in T2-weighted images (p = 0.008), prolongation of the central somato-sensory or motor conduction times (p = 0.004) and neurologic complications (p = 0.012) CONCLUSIONS: Treatment optimisation of the patient suffering cervical spondylotic myelopathy requires individualised evaluation. Prospective randomised studies are needed to answer the questions when and how to operate.

Adult↗
PubMed2002

[Anterior cervical diskectomy and interbody arthrodesis using Cloward technique: retrospective study of complications and radiological results of 167 cases].

PATIENTS AND METHODS: We performed a retrospective analysis of complications and radiological results in 167 patients surgically treated, for discal or spondylotic disease of the cervical spine, with Cloward procedure. Using uni and multivariate analysis, we tried to identify risk factors that might be correlated with surgical complications or radiological results. RESULTS: Surgical treatment was indicated for cervical radiculopathy in 68% of the patients and for myelopathy or radiculomyelopathy in the remaining 32%. The pathologic disease responsible of the symptomatology was soft disk herniation in 59% of the cases and spondylotic changes in 41%. The patients that underwent surgery because of myelopathy were one decade older, had a longer symptomatic period and presented multi-segmentary spondylotic disease with higher frequency than patients affected of radiculopathy. The most common segments operated were CS-C6 (44.3%) and C6-C7 (30.5%). Surgical mortality was 0.6% and morbidity 29.3%. Most of the complications were transient, although 4.8% of the patients developed permanent neurological deterioration. CONCLUSIONS: Complications were most commonly seen in the group of the patients undergoing surgery because of long-lasting myelopathy with multi-segmentary spondylotic disease, in those with vascular risk factors and in those operated of more than one segment. Surgeon anatomic knowledge and experience are critical for diminishing such complications. Non-union rate was 9.6%, and another 9.6% of the patients developed post-surgical kyphosis. Both factors correlated with the need of re-operation.

Adult↗
PubMed2001

BPS states in M theory and twistorial constituents.

We provide a complete algebraic description of Bogomol'nyi-Prasad-Sommerfield (BPS) states in M theory in terms of primary constituents that we call BPS preons. We argue that any BPS state preserving k of the 32 supersymmetries is a composite of (32-k) BPS preons. In particular, the BPS states corresponding to the basic M2 and M5 branes are composed of 16 BPS preons. By extending the M algebra to a generalized D = 11 conformal superalgebra osp(1/64) we relate the BPS preons with its fundamental representation, the D = 11 supertwistors.

Journal Article↗
PubMed2000

3'-untranslated regions of oxidative phosphorylation mRNAs function in vivo as enhancers of translation.

Recent findings have indicated that the 3'-untranslated region (3'-UTR) of the mRNA encoding the beta-catalytic subunit of the mitochondrial H(+)-ATP synthase has an in vitro translation-enhancing activity (TEA) [Izquierdo and Cuezva, Mol. Cell. Biol. (1997) 17, 5255-5268; Izquierdo and Cuezva, Biochem. J. (2000) 346, 849-855]. In the present work, we have expressed chimaeric plasmids that encode mRNA variants of green fluorescent protein in normal rat kidney and liver clone 9 cells to determine whether the 3'-UTRs of nuclear-encoded mRNAs involved in the biogenesis of mitochondria have an intrinsic TEA. TEA is found in the 3'-UTR of the mRNAs encoding the alpha- and beta-subunits of the rat H(+)-ATP synthase complex, as well as in subunit IV of cytochrome c oxidase. No TEA is present in the 3'-UTR of the somatic mRNA encoding rat mitochondrial transcription factor A. Interestingly, the TEA of the 3'-UTR of mRNAs of oxidative phosphorylation is different, depending upon the cell type analysed. These data provide the first in vivo evidence of a novel cell-specific mechanism for the control of the translation of mRNAs required in mitochondrial function.

3' Untranslated Regions↗
PubMed2000

Internal-ribosome-entry-site functional activity of the 3'-untranslated region of the mRNA for the beta subunit of mitochondrial H+-ATP synthase.

Translation in vitro of the mammalian nucleus-encoded mRNA for the beta subunit of mitochondrial H(+)-ATP synthase (beta-mRNA) of oxidative phosphorylation is promoted by a 150 nt translational enhancer sequence in the 3'-untranslated region (3' UTR). Titration of the eukaryotic initiation factor eIF4E with cap analogue revealed that translation of capped beta-mRNA was pseudo-cap independent. The 3' UTR of beta-mRNA stimulates the translation of heterologous uncapped mRNA species, both when the 3' UTR is placed at the 3' end and at the 5' end of the transcripts. The 3' UTRs of the alpha subunit of mitochondrial H(+)-ATP synthase (alpha-F1-ATPase) and subunit IV of cytochrome c oxidase (COX IV) mRNA species, other nucleus-encoded transcripts of oxidative phosphorylation, do not have the same activity in translation as the 3' UTR of beta-mRNA. On dicistronic RNA species, the 3' UTR of beta-mRNA, and to a smaller extent that of COX IV mRNA, is able to promote the translation of the second cistron to a level comparable to the activity of internal ribosome entry sites (IRESs) described in picornavirus mRNA species. These results indicate that the 3' UTRs of certain mRNA species of oxidative phosphorylation have IRES-like functional activity. Riboprobes of the active 3' UTRs on dicistronic assays formed specific RNA-protein complexes when cross-linked by UV to proteins of the lysate, suggesting that cytoplasmic translation of the mRNA species bearing an active 3' UTR is assisted by specific RNA-protein interactions.

3' Untranslated Regions↗
PubMed2000

A conserved mechanism for controlling the translation of beta-F1-ATPase mRNA between the fetal liver and cancer cells.

To characterize the mechanisms governing the biogenesis of mitochondria in cancer, we studied the mitochondrial phenotype and the mechanisms controlling the expression of the beta subunit of the mitochondrial H(+)-ATP synthase (beta-F1-ATPase) gene in the rat FAO and AS30D hepatomas. When compared with normal adult rat liver, the relative cellular content of the mitochondrial beta-F1-ATPase and glutamate dehydrogenase, as well as of mitochondrial DNA, was severely reduced in both cell lines. A paradoxical increase in the cellular abundance of beta-F1-ATPase mRNA was observed in cancer cells. Run-on transcription assays and the estimation of mRNA half-lives revealed that the increased abundance of beta-F1-ATPase mRNA results from the stabilization of the transcript in cancer. In vitro translation assays revealed a specific inhibition of the synthesis of the beta-precursor when translation reactions were carried out in the presence of extracts derived from cancer cells. The inhibitory effect was recapitulated using an RNA chimera that contained the 3'-untranslated region of beta-F1-ATPase mRNA. Hepatoma extracts also contained an increased activity of the developmentally regulated translation-inhibitory proteins that bind the 3'-untranslated region of beta-F1-ATPase mRNA. The results indicate that the expression of this gene in hepatoma cells is controlled by the same mechanisms that regulate its expression in the liver during fetal development.

3' Untranslated Regions↗
PubMed1997

Subcellular structure containing mRNA for beta subunit of mitochondrial H+-ATP synthase in rat hepatocytes is translationally active.

We have recently reported that the nuclear-encoded mRNA for the beta subunit of mitochondrial H+-ATP synthase (beta-mRNA) is localized in rounded, electron-dense clusters in the cytoplasm of rat hepatocytes. Clusters of beta-mRNA are often found in close proximity to mitochondria. These findings suggested a role for these structures in controlling the cytoplasmic expression and sorting of the encoded mitochondrial precursor. Here we have addressed the question of whether the structures containing beta-mRNA are translationally active. For this purpose a combination of high-resolution in situ hybridization and immunocytochemical procedures was used. Three different co-localization criteria showed that beta-mRNA-containing structures always revealed positive immunoreactive signals for mitochondrial H+-ATP synthase (F1-ATPase), ribosomal and hsc70 proteins. Furthermore, clusters show evidence in situ of developmental changes in the translational efficiency of the beta-mRNA. These findings suggest that structures containing beta-mRNA are translationally active irrespective of their cytoplasmic location. The immunocytochemical quantification of the cytoplasmic presentation of hsc70 in the hepatocyte reveals that approx. 86% of the protein has a dispersed distribution pattern. However, the remaining hsc70 is presented in clusters of which only half reveal positive hybridization for beta-mRNA. The interaction of hsc70 with the beta-F1-ATPase precursor protein is documented by the co-localization of F1-ATPase immunoreactive material within cytoplasmic clusters of hsc70 and by the co-immunoprecipitation of hsc70 with the beta-subunit precursor from liver post-mitochondrial supernatants. Taken together, these results suggest a role for hsc70 in the translation/sorting pathway of the mammalian precursor of the beta-F1-ATPase protein.

Animals↗
PubMed1997

mRNA encoding the beta-subunit of the mitochondrial F1-ATPase complex is a localized mRNA in rat hepatocytes.

Subcellular mRNA localization has emerged as a mechanism for regulation of gene expression and protein-sorting pathways. Here we describe the different cytoplasmic presentation in rat hepatocytes of two nuclear mRNA species encoding subunits alpha and beta of the mitochondrial F1-ATPase complex. alpha-F1-ATPase mRNA is dispersed and scattered in the cytoplasm. In contrast, beta-F1-ATPase mRNA appears in rounded electron-dense clusters, often in close proximity to mitochondria. Hybridization experiments with beta2-microglobulin and beta-actin cDNA species reveal an expected subcellular distribution pattern of the mRNA species and a non-clustered appearance. Development does not alter the presentation of beta-F1-ATPase mRNA hybrids, although it affects the relative abundance of beta-F1-ATPase mRNA clusters in the cytoplasm of the hepatocyte. These findings illustrate in vivo the existence of two different sorting pathways for the nuclear-encoded mRNA species of mitochondrial proteins. High-resolution immunocytochemistry and immunoprecipitation experiments allowed the identification of the beta-subunit precursor in the cytoplasm of the hepatocyte, also suggesting a post-translational import pathway for this precursor protein. It is suggested that the localization of beta-F1-ATPase mRNA in a subcellular structure of the hepatocyte might have implications for the control of gene expression at post-transcriptional levels during mitochondrial biogenesis in mammals.

Animals↗
PubMed1997

Gene therapy in brain tumours: implications of the size of glioblastoma on its curability.

The authors have used the thymidine kinase/ganciclovir system to block glioblastoma multiforme neoplastic cells in vivo, both in experimental animals and in two patients in which the more conventional therapies had been unsuccessful. In the Wistar rat it was found that the curability potential of the system is correlated with tumoral volume. Tumours smaller than 20 mm3 can be cured with defective retrovirus that do not carry the Herpes simplex thymidine kinase (Hsvtk) gene. While tumours smaller than 150 mm3 can regress totally by the kinase/ganciclovir system, those above that size cannot be cured by this treatment. In humans the situation seems very similar in that the authors have been unable either to reduce the tumour size of recurrent patients with tumour volumes larger than 100 cm2 applying the standard thymidine kinase/ganciclovir gene therapy or to prolong their survival time more than 8 months [7]. When a combination of size reduction by neurosurgery and gene therapy was used the survival time increased considerably. Two patients have been treated by partial surgery and repeated treatment with thymidine kinase/ganciclovir through an Ommaya reservoir connected to a catheter leading into the tumour cavity. The magnetic resonance imaging (MRI) of these patients show only a residual tumoral growth along side the tumoral bed. The procedure may be partially controlling the proliferation of cancerous cells, because, these two patients having recurrent glioblastoma, are alive 11 and 17 months after the beginning of the treatment.

Animals↗
PubMed1997

Mitochondrial biogenesis in the liver during development and oncogenesis.

The analysis of the expression of oxidative phosphorylation genes in the liver during development reveals the existence of two biological programs involved in the biogenesis of mitochondria. Differentiation is a short-term program of biogenesis that is controlled at post-transcriptional levels of gene expression and is responsible for the rapid changes in the bioenergetic phenotype of mitochondria. In contrast, proliferation is a long-term program controlled both at the transcriptional and post-transcriptional levels of gene expression and is responsible for the increase in mitochondrial mass in the hepatocyte. Recently, a specific subcellular structure involved in the localization and control of the translation of the mRNA encoding the beta-catalytic subunit of the H(+)-ATP synthase (beta-mRNA) has been identified. It is suggested that this structure plays a prominent role in the control of mitochondrial biogenesis at post-transcriptional levels. The fetal liver has many phenotypic manifestations in common with highly glycolytic tumor cells. In addition, both have a low mitochondrial content despite a paradoxical increase in the cellular representation of oxidative phosphorylation transcripts. Based on the paradigm provided by the fetal liver we hypothesize that the aberrant mitochondrial phenotype of fast-growing hepatomas represents a reversion to a fetal program of expression of oxidative phosphorylation genes by the activation, or increased expression, of an inhibitor of beta-mRNA translation.

Animals↗
PubMed1997

Control of the translational efficiency of beta-F1-ATPase mRNA depends on the regulation of a protein that binds the 3' untranslated region of the mRNA.

The expression of the nucleus-encoded beta-F1-ATPase gene of oxidative phosphorylation is developmentally regulated in the liver at both the transcriptional and posttranscriptional levels. In this study we have analyzed the potential mechanisms that control the cytoplasmic expression of beta-F1-ATPase mRNA during liver development. Remarkably, a full-length 3' untranslated region (UTR) of the transcript is required for its efficient in vitro translation. When the 3' UTR of beta-F1-ATPase mRNA is placed downstream of a reporter construct, it functions as a translational enhancer. In vitro translation experiments with full-length beta-F1-ATPase mRNA and with a chimeric reporter construct containing the 3' UTR of beta-F1-ATPase mRNA suggested the existence of an inhibitor of beta-F1-ATPase mRNA translation in the fetal liver. Electrophoretic mobility shift assays and UV cross-linking experiments allowed the identification of an acutely regulated protein (3'betaFBP) of the liver that binds at the 3' UTR of beta-F1-ATPase mRNA. The developmental profile of 3'betaFBP parallels the reported changes in the translational efficiency of beta-F1-ATPase mRNA during development. Fractionation of fetal liver extracts revealed that the inhibitory activity of beta-F1-ATPase mRNA translation cofractionates with 3'-UTR band-shifting activity. Compared to other tissues of the adult rat, kidney and spleen extracts showed very high expression levels of 3'betaFBP. Translation of beta-F1-ATPase mRNA in the presence of kidney and spleen extracts further supported a translational inhibitory role for 3'betaFBP. Mapping experiments and a deletion mutant of the 3' UTR revealed that the cis-acting element for binding 3'betaFBP is located within a highly conserved region of the 3' UTR of mammalian beta-F1-ATPase mRNAs. Overall, we have identified a mechanism of translational control that regulates the rapid postnatal differentiation of liver mitochondria.

ADP-Ribosylation Factors↗
PubMed1996

Transient activation of mitochondrial translation regulates the expression of the mitochondrial genome during mammalian mitochondrial differentiation.

Regulation of the expression of the nuclear-encoded beta-subunit of H(+)-ATP synthase (beta-F1-ATPase) gene of oxidative phosphorylation during differentiation of liver mitochondria is mainly exerted at two post-transcriptional levels affecting both the half-life [Izquierdo, Ricart, Ostronoff, Egea and Cuezva (1995) J. Biol. Chem. 270, 10342-10350] and translational efficiency [Luis, Izquierdo, Ostronoff, Salinas, Santarén and Cuezva (1993) J. Biol. Chem. 268, 1868-1875] of the transcript. Herein, we have studied the expression of the mitochondrial (mt) genome during differentiation of rat liver mitochondria in an effort to elucidate the mechanisms of nucleo-mitochondrial cross-talk during biogenesis of the organelle. Estimation of the relative cellular representation of met-DNA in liver reveals a negligible increase in mt-DNA copy number during organelle differentiation. Concurrently, the lack of changes in transcription rates of the mt-DNA "in organello', as well as in steady-state levels of the mt-transcripts, suggests that organelle differentiation is not controlled by an increase in transcription of the mt-genome. However, translation rates in isolated mitochondria revealed a transient 2-fold increase immediately after birth. Interestingly, the transient activation of mitochondrial translation at this stage of liver development is dependent on the synthesis of proteins in cytoplasmic polyribosomes. These findings support the hypothesis that the expression of nuclear and mitochondrial genes during biogenesis of mammalian mitochondria is developmentally regulated by a post-transcriptional mechanism that involves concerted translational control of both genomes.

Aging↗
PubMed1996

[Tracheobronchial amyloidosis: apropos of 3 cases].

We report 3 cases of tracheobronchial amyloidosis starting with post-obstructive pneumonitis, suggesting underlying neoplasm. The diagnosis was by fiberoptic bronchoscopy. We also describe radiological findings and their usefulness, therapeutic options, and course of disease.

Aged↗
PubMed1996

[Videothoracoscopy in the surgical treatment of pneumothorax: report of 46 cases].

We report our 3-years experience with video-thoracoscopy for pneumothorax. Forty-six endoscopies (34 men, 12 women; mean age 27 +/- 9 years) were performed. Patients were under general anesthesia and intubation was selective. The conventional approach was used, with 3 incisions through which the camera and endoscopic instruments were inserted. Results were good in 39 (84.7%) patients. Pneumothorax recurred in 4 (8.7%) patients during the 3 years of follow-up. Thoracotomy was performed in 3 patients, because of lack of lung expansion in 1, persistent leak in another and encapsulated empyema in the third. Mean hospital stay after surgery was 7.3 days. Video-thoracoscopy can be considered a good therapeutic alternative to thoracotomy in the surgical treatment of patients with pneumothorax.

Adult↗