Expression of transcriptional units using transmissible gastroenteritis coronavirus derived minigenomes and full-length cDNA clones.
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Animals↗
Biomedical subjects
S Alonso
Publications and source records attributed to S Alonso.
[Diagnostic utility of hepatic hemodynamics study in hepatoportal sclerosis].
AIM: To evaluate the diagnostic utility of catheterization of the suprahepatic veins in patients with suspected non-cirrhotic portal hypertension as well as to characterize the clinical features and evolution of this process. PATIENTS AND METHODS: Hepatic hemodynamics studies, transjugular biopsy and venography were performed in seven patients with suspected non-cirrhotic portal hypertension. In all patients the combination of the three procedures gave the diagnosis of hepatoportal sclerosis, which was subsequently confirmed by direct portography and percutaneous or laparoscopic liver biopsy. RESULTS: Three patients presented esophageal variceal bleeding at diagnosis. Only one patient required intrahepatic shunting due to refractory bleeding. None of the patients required surgical shunting or presented alterations in liver function. CONCLUSIONS: Hepatic hemodynamics study with transjugular biopsy and venography is an effective procedure in the diagnosis of hepatoportal sclerosis and in most cases invasive confirmatory tests are not required. The course of the disease is relatively benign if variceal bleeding is controlled. The treatment of choice in these patients is pharmacological and endoscopic.
Adult↗
[Predictive factors of the mortality of digestive hemorrhage caused by esophageal varices in elderly patients].
Complications of liver cirrhosis are increasingly frequent in elderly patients due to increased life expectancy and better management of cirrhotic patients. However, the influence of this condition on the evolution of variceal bleeding has not been well established. The aim of the present study was to determine the characteristics of esophagogastric variceal bleeding in elderly patients and the possible influence of advanced age on hemorrhage-related mortality. We analyzed 321 episodes of variceal bleeding in 227 cirrhotic patients. One hundred and thirteen (35.2%) episodes occurred in patients older than 65 years. No differences were found among patients older or younger than this age in terms of bleeding characteristics or Child-Pugh score. Patients older than 65 years more frequently presented serious associated diseases, hepatocellular carcinoma and hepatic encephalopathy during the episode (52.7% vs. 14%, p < 0.001; 19.7% vs. 8.7%, p = 0.01 and 17.4% vs. 10%, p = 0.09 respectively). Although hemorrhage-related mortality was higher in elderly patients (23.2% vs. 13.5%, p = 0.04), only the Child-Pugh score, definitive hemostasis, hepatocellular carcinoma and the development of encephalopathy or bacterial infection were independent predictive factors of mortality. A considerable proportion of the patients with esophagogastric variceal bleeding were older than 65 years. Advanced age does not independently influence mortality due to variceal bleeding.
Aged↗
Dynamic expression patterns of the new protocadherin families CNRs and Pcdh-gamma during mouse odontogenesis: comparison with reelin expression.
Protocadherins are transmembrane glycoproteins belonging to the cadherin superfamily of molecules, which are involved in many biological processes such as cell adhesion, cytoskeletal organization and morphogenesis. Protocadherins generally exhibit only moderate adhesive activity and are highly expressed in the nervous system. Here, we report on the expression pattern of two novel families of protocadherins (CNRs and Pcdh-gamma) during rodent teeth development. Furthermore, we compare their expression with that of reelin, which is the potential ligand of CNRs. Throughout odontogenesis, CNRs, Pcdh-gamma and reelin show dynamic spatiotemporal expression patterns, which relate to both morphogenesis and cell differentiation events.
Animals↗
Randomized controlled trial of aspiration needle versus automated biopsy device for transjugular liver biopsy.
PURPOSE: The efficacy and safety of transjugular liver biopsy used to obtain liver specimens in patients with coagulation disorders have been widely proven. However, histopathologic examination is not always possible because of fragmented samples provided by the aspiration technique. Recently, an automated device with a Tru-Cut-type needle was designed. In this randomized controlled trial, the use of this new device is compared with the traditional method in terms of efficacy and safety. METHOD: Fifty-six patients were included in the study; 28 were randomized to undergo the aspiration technique and 28 were randomized to undergo the automated biopsy technique. RESULTS: Correct positioning of the device was achieved in 93% of patients undergoing the aspiration technique and 96% of patients undergoing the automated biopsy technique (P = NS). Mean duration of the procedure and total number of passes were significantly higher in the aspiration needle group than in the automated device group (22.6 min +/- 12.6 vs 15.5 min +/- 9.4; P = .03, and 3.3 min +/- 1.9 vs 1.5 min +/- 0.63; P < .001, respectively). The number of portal tracts was significantly higher in the automated device group (4.7 +/- 2.5 vs. 2.7 +/- 3.4; P < .05). Adequate specimens for histopathologic evaluation were obtained in 26 patients in the automated device group and 24 patients in the aspiration needle group (92.8% vs 85.7%; P = NS), but a definite histopathologic diagnosis was more frequently obtained with the automated biopsy device (68% vs 43%; P = .05). No significant differences were observed in complication rates (7.14% vs. 10.7%; P = NS). CONCLUSION: The automated biopsy device for transjugular liver biopsy is more effective than an aspiration needle in obtaining good samples for a definite histologic diagnosis.
Adult↗
Spiral CT diagnosis of isolated systemic supply to normal lung merging from the coeliac trunk.
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Adult↗
Role of ADP-ribosyltransferase activity of pertussis toxin in toxin-adhesin redundancy with filamentous hemagglutinin during Bordetella pertussis infection.
Pertussis toxin (PT) and filamentous hemagglutinin (FHA) are two major virulence factors of Bordetella pertussis. FHA is the main adhesin, whereas PT is a toxin with an A-B structure, in which the A protomer expresses ADP-ribosyltransferase activity and the B moiety is responsible for binding to the target cells. Here, we show redundancy of FHA and PT during infection. Whereas PT-deficient and FHA-deficient mutants colonized the mouse respiratory tract nearly as efficiently as did the isogenic parent strain, a mutant deficient for both factors colonized substantially less well. This was not due to redundant functions of PT and FHA as adhesins, since in vitro studies of epithelial cells and macrophages indicated that FHA, but not PT, acts as an adhesin. An FHA-deficient B. pertussis strain producing enzymatically inactive PT colonized as poorly as did the FHA-deficient, PT-deficient strain, indicating that the ADP-ribosyltransferase activity of PT is required for redundancy with FHA. Only strains producing active PT induced a local transient release of tumor necrosis factor alpha (TNF-alpha), suggesting that the pharmacological effects of PT are the basis of the redundancy with FHA, through the release of TNF-alpha. This may lead to damage of the pulmonary epithelium, allowing the bacteria to colonize even in the absence of FHA.
Adhesins, Bacterial↗
Production of Neisseria meningitidis transferrin-binding protein B by recombinant Bordetella pertussis.
Neisseria meningitidis serogroup B infections are among the major causes of fulminant septicemia and meningitis, especially severe in young children, and no broad vaccine is available yet. Because of poor immunogenicity of the serogroup B capsule, many efforts are now devoted to the identification of protective protein antigens. Among those are PorA and, more recently, transferrin-binding protein B (TbpB). In this study, TbpB of N. meningitidis was genetically fused to the N-terminal domain of the Bordetella pertussis filamentous hemagglutinin (FHA), and the fha-tbpB hybrid gene was expressed in B. pertussis either as a plasmid-borne gene or as a single copy inserted into the chromosome. The hybrid protein was efficiently secreted by the recombinant strains, despite its large size, and was recognized by both anti-FHA and anti-TbpB antibodies. A single intranasal administration of recombinant virulent or pertussis-toxin-deficient, attenuated B. pertussis to mice resulted in the production of antigen-specific systemic immunoglobulin G (IgG), as well as local IgG and IgA. The anti-TbpB serum antibodies were of the IgG1, IgG2a, and IgG2b isotypes and were found to express complement-mediated bactericidal activity against N. meningitidis. These observations indicate that recombinant B. pertussis may be a promising vector for the development of a mucosal vaccine against serogroup B meningococci.
Adhesins, Bacterial↗
External-pH-dependent expression of the maltose regulon and ompF gene in Escherichia coli is affected by the level of glycerol kinase, encoded by glpK.
The expression of the maltose system in Escherichia coli is regulated at both transcriptional and translational levels by the pH of the growth medium (pHo). With glycerol as the carbon source, transcription of malT, encoding the transcriptional activator of the maltose regulon, is weaker in acidic medium than in alkaline medium. malT transcription became high, regardless of the pHo, when glycerol-3-phosphate or succinate was used as the carbon source. Conversely, malT expression was low, regardless of the pHo, when maltose was used as the carbon source. The increase in malT transcription, associated with the pHo, requires the presence of glycerol in the growth medium and the expression of the glycerol kinase (GlpK). Changes in the level of glpK transcription had a great effect on malT transcription. Indeed, a glpFKX promoter-down mutation has been isolated, and in the presence of this mutation, malT expression was increased. When glpK was expressed from a high-copy-number plasmid, the glpK-dependent reduced expression of the maltose system became effective regardless of the pHo. Analysis of this repression showed that a malTp1 malTp10 promoter, which is independent of the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex, was no longer repressed by glpFKX amplification. Thus, GlpK-dependent repression of the maltose system requires the cAMP-CRP complex. We propose that the pHo may affect a complex interplay between GlpK, the phosphotransferase-mediated uptake of glucose, and the adenylate cyclase.
ATP-Binding Cassette Transporters↗
[Fasciola hepatica infestation: infrequent cause of cholestasis].
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Cholestasis↗
Rigid multilamellar bilayer cooperativity is modified by non covalently linked neuraminic-5-acid: a spectrophotometric determination.
By means of recording a simple serie of merocyanine 540 spectra, we present a method to calculate the value proportional to co-operative unit size of membranes (n). Our calculations, applied to different liposomal samples processed in the presence or absence of sugars, in high or low ionic strength showed two main results. First, that any temperature cycling in high ionic strength of rigid DPPC bilayers will modify the membrane cooperativity. Second, the presence of polysaccharide Neu-5-ac in solution will always produce a strong drop in co-operativity of a rigid membrane of DPPC, whenever the negative charge is fully exposed. This last result indicates a differential ability of charged Neu-5-ac to disrupt a rigid membrane structure, even in the absence of a covalent linkage and--remarkably-in fully hydrated media.
1,2-Dipalmitoylphosphatidylcholine↗
Integrated analysis of sequence evolution and population history using hypervariable compound haplotypes.
We have examined compound haplotypes from a highly informative region of human chromosome 16, in which information from the rapid evolution of a highly unstable minisatellite is integrated with data on the longer-term evolution of this segment from 10 flanking substitutional polymorphisms. Combined with sequence data from non-human primates, analysis of relationships between these compound haplotypes allows the reconstruction of a rooted network of the evolutionary pathways between them. Most relationships can be explained via simple substitutional mutations, although the origins of some haplotypes involve recurrent events at a hotspot for substitutional mutation and/or gene conversion. For compound haplotypes including the minisatellite array, the network found in a range of world-wide populations constitutes a highly informative data set for the analysis of population history (437 different compound haplotypes were discriminated among 658 studied). Since the mutation rates and processes of the minisatellite array are known from direct studies, ages for individual lineages have been estimated using associated minisatellite diversity. These analyses suggest that the higher information content and sampling depth of these compound haplotypes may allow more precise calibration of lineage ages than is possible using coalescent analysis of DNA sequence. Using this method we have dated the oldest Eurasian lineage as 52,000-66,000 years and the oldest European specific lineage as 37,600-56,200 years.
Africa↗
Brownian motion of spiral waves driven by spatiotemporal structured noise
Spiral chemical waves subjected to a spatiotemporal random excitability are experimentally and numerically investigated in relation to the light-sensitive Belousov-Zhabotinsky reaction. Brownian motion is identified and characterized by an effective diffusion coefficient which shows a rather complex dependence on the time and length scales of the noise relative to those of the spiral. A kinematically based model is proposed whose results are in good qualitative agreement with experiments and numerics.
Journal Article↗
Zinc burns: a rare burn injury.
A patient was presented with significant burns resulting from a workplace accident in a zinc production unit. This occurred as a result of the spontaneous combustion of zinc bleed under high pressure. The patient sustained burns to the face, body, and hands and suffered significant injury to the left cornea. Computed imaging revealed solid particles in the ethmoid sinus and also in the right nasal fossa, dissecting the right lacrimal duct. Photographic documentation is presented. This injury was potentially preventable and resulted from poor observance of safety procedures.
Accidents, Occupational↗
New virulence-activated and virulence-repressed genes identified by systematic gene inactivation and generation of transcriptional fusions in Bordetella pertussis.
An in silico scan of the partially completed genome sequence of Bordetella pertussis and analyses of transcriptional fusions generated with a new integrational vector were used to identify new potential virulence genes. The genes encoding a putative siderophore receptor, adhesins, and an autotransporter protein appeared to be regulated in a manner similar to Bordetella virulence genes by the global virulence regulator BvgAS. In contrast, the gene encoding a putative intimin-like protein appeared to be repressed under conditions of virulence.
Amino Acid Sequence↗
Paclitaxel/gemcitabine administered every two weeks in advanced breast cancer: preliminary results of a phase II trial.
The purpose of this study was to evaluate the toxicity and efficacy of paclitaxel/gemcitabine administered every 2 weeks in the first-line treatment of advanced breast cancer. Forty-three chemonaive patients with histologically confirmed metastatic breast carcinoma were enrolled. Patients received paclitaxel 150 mg/m2 followed by gemcitabine 2,500 mg/m2, both on day I of a 14-day cycle, for a maximum of eight cycles. Thirty-four patients were evaluable for toxicity; 38 were evaluable for efficacy. The median age at the time of diagnosis was 54 years, the median performance status was 90, and the median number of lesions was three. Most patients (71%) had received prior adjuvant therapy. Grade 3 and 4 toxicity was limited to leukocytes (14% and 18%, respectively). Grade 3 toxicities (5% each) were thrombocytopenia, nausea and vomiting, elevation of aspartate transaminase, neurosensory, and constipation. One patient had neutropenia and fever. The objective response rate was 68% (21% complete response and 47% partial response); 18% had stable disease and 13% had partial disease. The preliminary evaluation of paclitaxel/gemcitabine given as a 2-week schedule to patients with untreated advanced breast carcinoma shows encouraging activity and a favorable toxicity profile.
Adult↗
Interference with virus and bacteria replication by the tissue specific expression of antibodies and interfering molecules.
Historically, protection against virus infections has relied on the use of vaccines, but the induction of an immune response requires several days and in certain situations, like in newborn animals that may be infected at birth and die in a few days, there is not sufficient time to elicit a protective immune response. Immediate protection in new born could be provided either by vectors that express virus-interfering molecules in a tissue specific form, or by the production of animals expressing resistance to virus replication. The mucosal surface is the largest body surface susceptible to virus infection that can serve for virus entry. Then, it is of high interest to develop strategies to prevent infections of these areas. Virus growth can be interfered intracellularly, extracellularly or both. The antibodies neutralize virus intra- and extracellularly and their molecular biology is well known. In addition, antibodies efficiently neutralize viruses in the mucosal areas. The autonomy of antibody molecules in virus neutralization makes them functional in cells different from those that produce the antibodies and in the extracellular medium. These properties have identified antibodies as very useful molecules to be expressed by vectors or in transgenic animals to provide resistance to virus infection. A similar role could be played by antimicrobial peptides in the case of bacteria. Intracellular interference with virus growth (intracellular immunity) can be mediated by molecules of very different nature: (i) full length or single chain antibodies; (ii) mutant viral proteins that strongly interfere with the replication of the wild type virus (dominant-negative mutants); (iii) antisense RNA and ribozyme sequences; and (iv) the product of antiviral genes such as the Mx proteins. All these molecules inhibiting virus replication may be used to obtain transgenic animals with resistance to viral infection built in their genomes. We have developed two strategies to target into mucosal areas either antibodies to provide immediate protection, or antigens to elicit immune responses in the enteric or respiratory surfaces in order to prevent virus infection. One strategy is based on the development of expression vectors using coronavirus derived defective RNA minigenomes, and the other relies on the development of transgenic animals providing virus neutralizing antibodies in the milk during lactation. Two types of expression vectors are being engineered based on transmissible gastroenteritis coronavirus (TGEV) defective minigenomes. The first one is a helper virus dependent expression system and the second is based on self-replicating RNAs including the information required to encode the TGEV replicase. The minigenomes expressing the heterologous gene have been improved by using a two-step amplification system based on cytomegalovirus (CMV) and viral promoters. Expression levels around 5 micrograms per 10(6) cells were obtained. The engineered minigenomes will be useful to understand the mechanism of coronavirus replication and for the tissue specific expression of antigen, antibody or virus interfering molecules. To protect from viral infections of the enteric tract, transgenic animals secreting virus neutralizing recombinant antibodies in the milk during lactation have been developed. Neutralizing antibodies with isotypes IgG1 or IgA were produced in the milk with titers of 10(6) in RIA that reduced virus infectivity by one million-fold. The recombinant antibodies recognized a conserved epitope apparently essential for virus replication. Antibody expression levels were transgene transgene copy number independent and were related to the transgene integration site. This strategy may be of general use since it could be applied to protect newborn animals against infections of the enteric tract by viruses or bacteria for which a protective MAb has been identified. Alternatively, the same strategy could be used to target the expression of antibio
Animals↗
Doppler duplex color localization of osteoid osteomas.
We present two cases of osteoid osteoma in adolescent boys. The lesions were located in the proximal metaphysis of the right tibia and left femoral diaphysis respectively. Doppler duplex color study demonstrated clearly the highly vascular nidus and its feeding artery in one case and only the feeding artery in the second. We believe these are the first descriptions of osteoid osteomas assessed with Doppler duplex color, which was also used as guidance for the percutaneous localization and biopsy.
Adolescent↗