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.

Publishing science in the digital age. The case of Neurocirugía.

Neurocirugía publishes a printed edition for subscribers, and also an electronic edition which is available online free of charge. The coexistence of these two formats raises some issues regarding their justification and their future evolution, e.g. why does a subscription- based journal offer free online access? Would it be wise to charge for -or somewhat limit- the electronic access to the Journal? How is the Internet changing the benefits to society that the Journal provides? Will the printed and the electronic edition of the Journal continue to coexist? This paper provides some answers and reflections on these questions. Many of our considerations are based on ideas that have been presented and discussed in a series of editorials in Neurocirugía (see Neurocirugía 17 (2), 2006); in this paper we reconsider, complement, and rearrange previous arguments to address the issues mentioned above. Based on an analysis of economic costs and of all the stakeholders involved (authors, readers, the Journal, the Spanish Society of Neurosurgery, and society as a whole), we justify the present coexistence of the two publishing formats, defend free online access, and provide our view on the expected evolution of the Journal. While we focus primarily on Neurocirugía, most of our reflections can be carried over to other scientific journals.

[Cervical myelopathy: retrospective analysis of surgical results in 53 cases treated by anterior cervical discectomy and interbody fusion]. / Mielopatía cervical: análisis retrospectivo de los resultados quirúrgicos de 54 pacientes tratados mediante descectomía y fusión intersomática por vía anterior.

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.

T-cell intracellular antigens function as tumor suppressor genes.

Knockdown of T-cell intracellular antigens TIA1 and TIAR in transformed cells triggers cell proliferation and tumor growth. Using a tetracycline-inducible system, we report here that an increased expression of TIA1 or TIAR in 293 cells results in reduced rates of cell proliferation. Ectopic expression of these proteins abolish endogenous TIA1 and TIAR levels via the regulation of splicing of their pre-mRNAs, and partially represses global translation in a phospho-eukaryotic initiation factor 2 alpha-dependent manner. This is accompanied by cell cycle arrest at G1/S and cell death through caspase-dependent apoptosis and autophagy. Genome-wide profiling illustrates a selective upregulation of p53 signaling pathway-related genes. Nude mice injected with doxycycline-inducible cells expressing TIA1 or TIAR retard, or even inhibit, growth of xenotumors. Remarkably, low expressions of TIA1 and TIAR correlate with poor prognosis in patients with lung squamous cell carcinoma. These findings strongly support the concept that TIA proteins act as tumor suppressor genes.

Thyroid hormones promote transcriptional activation of the nuclear gene coding for mitochondrial beta-F1-ATPase in rat liver.

Thyroid hormones acutely regulate gene expression of the beta-catalytic subunit of the mitochondrial F1-ATPase complex in the liver of hypothyroid rat neonates at either a transcriptional and/or post-transcriptional level [(1990) J. Biol. Chem. 265, 9090-9097]. Administration at birth of various thyroid hormone doses to hypothyroid newborn rats promote a rapid (1 h) increase in liver steady-state amounts of both beta-F1-ATPase protein and mRNA. Induction of the beta-F1-ATPase mRNA is coincident with an elevation in gene transcription detected using nascent RNA chains synthesized by isolated nuclei. These results suggest that thyroid hormones induction of postnatal mitochondrial differentiation in the liver of hypothyroid rat neonates is mostly triggered by transcriptional regulation of beta-F1-ATPase gene.

Immunological detection of the mitochondrial F1-ATPase alpha subunit in the matrix of rat liver peroxisomes. A protein involved in organelle biogenesis?

Rat liver peroxisomes contain in their matrix the alpha-subunit of the mitochondrial F1-ATPase complex. The identification of this protein in liver peroxisomes has been achieved by immunoelectron microscopy and subcellular fractionation. No beta-subunit of the mitochondrial F1-ATPase complex was detected in the peroxisomal fractions obtained in sucrose gradients or in Nycodenz pelletted peroxisomes. The consensus peroxisomal targeting sequence (Ala-Lys-Leu) is found at the carboxy terminus of the mature alpha-subunit from bovine heart and rat liver mitochondria. Due to the dual subcellular localization of the alpha-subunit and to the structural homologies that exist between this protein and molecular chaperones [(1990) Biol. Chem. 265, 7713-7716] it is suggested that the protein should perform another functional role(s) in both organelles, plus to its characteristic involvement in the regulation of mitochondrial ATPase activity.

Bisalbuminaemia in a Spanish family: characterization of the albumin variant.

A case of bisalbuminaemia has been found in Luarca, Asturias. At least two relatives also bear the trait. The variant albumin Luarca (Al Lu, gene notation Al(Lu)), the first to be found on the mainland of Spain, is described in terms of its electrophoretic mobilities and dye-binding properties. It is heat-stable but sensitive to storage, freezing, and thawing and it is the first albumin to show this property.

Learning from noisy information in FasArt and FasBack neuro-fuzzy systems.

Neuro-fuzzy systems have been in the focus of recent research as a solution to jointly exploit the main features of fuzzy logic systems and neural networks. Within the application literature, neuro-fuzzy systems can be found as methods for function identification. This approach is supported by theorems that guarantee the possibility of representing arbitrary functions by fuzzy systems. However, due to the fact that real data are often noisy, generation of accurate identifiers is presented as an important problem. Within the Adaptive Resonance Theory (ART), PROBART architecture has been proposed as a solution to this problem. After a detailed comparison of these architectures based on their design principles, the FasArt and FasBack models are proposed. They are neuro-fuzzy identifiers that offer a dual interpretation, as fuzzy logic systems or neural networks. FasArt and FasBack can be trained on noisy data without need of change in their structure or data preprocessing. In the simulation work, a comparative study is carried out on the performances of Fuzzy ARTMAP, PROBART, FasArt and FasBack, focusing on prediction error and network complexity. Results show that FasArt and FasBack clearly enhance the performance of other models in this important problem.

Emergency embolectomy of middle cerebral artery occlusion due to microcoil migration: case report.

We report a successful emergency embolectomy in a patient presenting a left middle cerebral artery occlusion by an embolizing microcoil that was being used to thrombose an aneurysm of the ophthalmic artery. In selected cases, emergency embolectomy can be considered as the treatment of distal embolization by the materials used in neuroendovascular procedures.

Hydatid cyst: unusual cause of unilateral exophthalmos.

Intraorbital hydatid cysts are encountered unusually on neurosurgical services. Recently, 3 patients with intraorbital hydatid cysts have been studied by the Neurosurgical Service of C. S. "La Paz." In two of them, a computed tomography (CT) scan was performed; we think that these are the first cases of this type to be studied with CT scans. In each case, the CT scan showed a circular mass with a density similar to that of the eye. Frequency, localization, symptomatology, and neuroradiological aspects of intraorbital hydatid cysts are described. The different surgical approaches also are discussed.

muARTMAP: use of mutual information for category reduction in Fuzzy ARTMAP.

A new architecture called muARTMAP is proposed to impact a category proliferation problem present in Fuzzy ARTMAP. Under a probabilistic setting, it seeks a partition of the input space that optimizes the mutual information with the output space, but allowing some training error, thus avoiding overfitting. It implements an inter-ART reset mechanism that permits handling exceptions correctly, thus using few categories, especially in high dimensionality problems. It compares favorably to Fuzzy ARTMAP and Boosted ARTMAP in several synthetic benchmarks, being more robust to noise than Fuzzy ARTMAP and degrading less as dimensionality increases. Evaluated on a real-world task, the recognition of handwritten characters, it performs comparably to Fuzzy ARTMAP, while generating a much more compact rule set.

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.

[Videothoracoscopy in the surgical treatment of pneumothorax: report of 46 cases]. / Videotoracoscopia en el tratamiento quirúrgico del neumotórax: a propósito de 46 casos.

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.

[Tracheobronchial amyloidosis: apropos of 3 cases]. / Amiloidosis traqueobronquial: a propósito de tres casos.

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.

[Lung resection surgery in patients with functional limits]. / Cirugía resectiva pulmonar en pacientes en el límite funcional.

To determine whether there exists in our area concordance between forced expiratory volume in one second (FEV1) estimated before surgery by ventilation/perfusion scintigraphy and real values after surgery in patients undergoing pneumonectomy and lobectomy. Prospective descriptive study. We studied 15 patients undergoing pneumonectomy (M/F 14:1, age 62 +/- 7.5 years) and 11 undergoing lobectomy (M/F 11:0 age 66 +/- 3.5 years) in the thoracic surgery unit of Hospital de Cruces between 1 March 1990 and 1 March 1993. The FEV1 of all patients before surgery was under 2.1 liters. Tumors were malignant in 23 patients and benign in 3. Ventilation/perfusion gammagrams were obtained for all patients before surgery in order to predict the loss of function after resection of the parenchyma. Two months after surgery spirometric testing was done. The FEV1 calculated based on the results of scintigraphy was compared to the real FEV1 after resection by way of graphic concordance and by calculation of a within-group correlation coefficient. A correlation coefficient of 0.82 (p < 0.001) was obtained for FEV1 estimated by ventilation and real FEV1 in patients who underwent pneumonectomy, indicating good concordance. The correlation coefficient was 0.59 (p < 0.001) indicating moderate agreement between FEV1 estimated by perfusion and real FEV1 after resection. Correlation was statistically insignificant in lobectomy patients (0.28 by the method of Ali and 0.35 by Wernly's; p = 0.19 and 0.13, respectively). Ventilation scintigraphy offers an acceptably reliable prediction of FEV1 after lung resection. The reliability of measurements estimated by scintigraphy in lobectomized patients is not acceptable.

Intracranial complications of frontal sinusitis. A report of two cases.

Two cases are reported of intracranial complications of sinusitis, unusual nowadays. They were caused by osteomyelitis of the frontal bone following chronic frontal sinusitis. These cases were distinguished by complete destruction of the posterior wall of the sinus involved: in one of the cases there was an acute central neurological disturbance caused by a cerebral abscess; in the other patient, who came for consultation because of a Pott's Puffy tumour, a sizeable epidural abscess was found.

[Anterior cervical diskectomy and interbody arthrodesis using Cloward technique: retrospective study of complications and radiological results of 167 cases]. / Discectomía cervical y artrodesis intersomática mediante técnica de Cloward: análisis retrospectivo de las complicaciones y los resultados radiológicos en 167 casos.

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.

[Elective cesarean section with epidural anesthesia in a pregnant woman with obstructive hypertrophic myocardiopathy]. / Cesárea electiva con anestesia epidural a una gestante con miocardiopatía hipertrófica obstructiva.

Hypertrophic obstructive myocardiopathy (HOM) is characterised by left ventricular hypertrophy, which causes dynamic obstruction at the exit of the chamber and diastolic dysfunction of the myocardium. The use of epidural anesthesia in patients with HOM is controversial due to the hemodynamic repercussions of reduced preloading and postloading that occur. A 28-year-old woman with HOM was scheduled for cesarean delivery at 36.5 weeks because of delayed intrauterine growth. Satisfactory epidural anesthesia was provided with 0.5% bupivacaine with prior invasive hemodynamic monitoring. Analgesic and anesthetic management of a full-term parturient with HOM is a major challenge for the anesthesiologist. Although elective cesarean under general anesthesia is traditionally suggested for such patients, vaginal delivery with epidural analgesia is currently also being used. However, experience in using epidural anesthesia for cesarean delivery is scarce. For our patient, epidural anesthesia with appropriate hemodynamic monitoring allowed surgery to take place without complications. We therefore believe that the technique might be useful for such patients.

Survival after lung metastasectomy for colorectal cancer: importance of previous liver metastasis as a prognostic factor.

AIMS: To analyse patient survival after the resection of lung metastases from colorectal carcinoma and specifically to verify whether presence of liver metastasis prior to lung metastasectomy affects survival. METHODS: All patients who, between 1998 and 2008, underwent lung metastasectomy due to colorectal cancer were included in the study. Kaplan-Meier survival analysis was performed with the log-rank test and Cox regression multivariate analysis. RESULTS: During this period, 101 metastasectomies were performed on 84 patients. The median age of patients was 65.4 years, and 60% of patients were male. The 30-day mortality rate was 2%, and incidence of complications was 7%. The overall survival was 72 months, with 3-and 5-year survival rates of 70% and 54%, respectively. A total of 17 patients (20%) had previously undergone resection of liver metastasis. No significant differences were found in the distribution of what were supposed to be the main variables between patients with and without previous hepatic metastases. Multivariate analysis identified the following statistically significant factors affecting survival: previous liver metastasectomy (p = 0.03), tumour-infiltrated pulmonary lymph nodes (p = 0.04), disease-free interval ≥ 48 months (p = 0.03), and presence of more than one lung metastasis (p < 0.01). In patients with previous liver metastasis, the shorter the time between primary colorectal surgery and the hepatectomy, the lower the survival rate after pulmonary metastasectomy (p = 0.048). CONCLUSIONS: A previous history of liver metastasis shortens survival after lung metastasectomy. The time between hepatic resection and lung metastasectomy does not affect survival; however, patients with synchronous liver metastasis and colorectal neoplasia have poorer survival rates than those with metachronous disease.