Magnetic resonance imaging of acute infarction of the anterior spinal cord.
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Biomedical subjects
Publications and source records attributed to J Alvarez.
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Vegetative and reproductive phases alternate regularly during sympodial growth in tomato. In wild-type 'indeterminate' plants, inflorescences are separated by three vegetative nodes. In 'determinate' plants homozygous for the recessive allele of the SELF-PRUNING (SP) gene, sympodial segments develop progressively fewer nodes until the shoot is terminated by two consecutive inflorescences. We show here that the SP gene is the tomato ortholog of CENTRORADIALIS and TERMINAL FLOWER1, genes which maintain the indeterminate state of inflorescence meristems in Antirrhinum and Arabidopsis respectively. The sp mutation results in a single amino acid change (P76L), and the mutant phenotype is mimicked by overexpressing the SP antisense RNA. Ectopic and overexpression of the SP and CEN transgenes in tomato rescues the 'indeterminate' phenotype, conditions the replacement of flowers by leaves in the inflorescence and suppresses the transition of the vegetative apex to a reproductive shoot. The SELF-PRUNING gene is expressed in shoot apices and leaves from very early stages, and later in inflorescence and floral primordia as well. This expression pattern is similar to that displayed by the tomato ortholog LEAFY and FLORICAULA. Comparison of the sympodial, day-neutral shoot system of tomato and the monopodial, photoperiod-sensitive systems of Arabidopsis and Antirrhinum suggests that flowering genes that are required for the processing of floral induction signals in Arabidopsis and Antirrhinum are required in tomato to regulate the alternation between vegetative and reproductive cycles in sympodial meristems.
A 69-year-old man was admitted to the Intensive Care Recovery Unit after heart surgery, carrying an intra balloon counterpulsation (IABCP) device inserted percutaneously days before surgery to provide hemodynamic support and which was still required after surgery. Fifteen days after insertion, blood was observed in the safety chamber. Surgical removal of the catheter was required when attempts to remove it manually failed. The balloon was seen to be perforated and clotted blood was found inside. We believe that long-term maintenance of IABCP carries high risk of perforation and entry of blood, which will clot, as well as of catheter entrapment unless removal is prompt.
BACKGROUND: Previous studies have shown the diagnostic relevance of the so-called free testosterone/cortisol ratio (FTCR). A condition of overtraining might indeed exist in an athlete when at least one of the two following criteria are observed: a) a FTCR value lower than 0.00035 (FT in nmol x L(-1) and C in micromol x L(-1)); and b) a decrease in the FTCR of 30% or more. On the other hand, no previous research has studied the incidence of overtraining in special military units as a result of their demanding training programs. HYPOTHESIS: A percentage of recruits of the Spanish special military Unit, "Grupo de Operaciones Especiales," (GOES) might be overtrained. It was the purpose of our study to analyze the effects on the FTCR of an intense physical training program performed by recruits of the GOES. METHODS: Before (PRE) and after (POST) an 8-wk training program, respectively, the following measurements were made in 42 recruits of the GOES: hematological and hormonal parameters (FTCR), aerobic and anaerobic tests, and strength and power tests. RESULTS: A high incidence (10 subjects, 23.8% of total) of overtraining existed among conscripts, as determined by the absolute criterium of a decline in the FCTR of 30% or more when comparing PRE and POST values. Additionally, overtraining was associated with a decrease in performance (i.e., isometric strength, vertical jump, Wingate tests). CONCLUSIONS: In addition to some conventional measurements of performance, the FTCR might be used to monitor exercise training in military units, in order to prevent overtraining.
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OBJECTIVE: To study the time course of thyroid function abnormalities and their relation to outcome in patients with septic shock. DESIGN: Prospective study in a cohort of consecutive patients. SETTING: Intensive Care Unit in a University Hospital. PATIENTS AND METHODS: We studied 27 patients (mean age 50 +/- 19 years, Apache II score 18.4 +/- 5.2, 15 survivors) diagnosed of septic shock. Total T4 (T4) and total T3 (T3) (RIA) were determined on days 1 and 5 after admission. We also measured TSH (ultrasensitive RIA) at 08.00, 20.00 and 01.00 hours (on days 1 and 5), and the TSH response to TRH (400 microg intravenous) on days 2 and 6. Data are mean +/- SD. RESULTS: Whereas low thyroid hormones concentrations were present on day 1 in all patients, only survivors presented a significant increase in T3 and T4 on day 5. Basal TSH levels and the area under the curve of the TSH response to TRH on day 2 were significantly higher in survivors than in non survivors (0.89 +/- 0.63 vs. 0.34 +/- 0.42 microIU/ml, and 229 + 157 vs. 101 + 101). The normal nocturnal (01.00 hr) surge of TSH (the difference between TSH concentrations at 8 am and at 1 am) was abolished in both survivors and non survivors on day 1 but it was recovered on day 5 only in survivors. CONCLUSIONS: Our data indicate that patients with septic shock present an altered hypothalamic-pituitary-thyroid axis, and that survivors thyroid function differs from that of non survivors shortly after diagnosis. Survivors are characterised by a greater TSH response to TRH, indicating a less deranged hypothalamic-pituitary-thyroid axis. Thyroid function improves in survivors, but not in non survivors, during the course of their illness.
Two recombinant aequorin isoforms with different Ca2+ affinities, specifically targeted to the endoplasmic reticulum (ER), were used in parallel to investigate free Ca2+ homeostasis in the lumen of this organelle. Here we show that, although identically and homogeneously distributed in the ER system, as revealed by both immunocytochemical and functional evidence, the two aequorins measured apparently very different concentrations of divalent cations ([Ca2+]er or [Sr2+]er). Our data demonstrate that this contradiction is due to the heterogeneity of the [Ca2+] of the aequorin-enclosing endomembrane system. Because of the characteristics of the calibration procedure used to convert aequorin luminescence into Ca2+ concentration, the [Ca2+]er values obtained at steady state tend, in fact, to reflect not the average ER values, but those of one or more subcompartments with lower [Ca2+]. These subcompartments are not generated artefactually during the experiments, as revealed by the dynamic analysis of the ER structure in living cells carried out by means of an ER-targeted green fluorescent protein. When the problem of ER heterogeneity was taken into account (and when Sr2+ was used as a Ca2+ surrogate), the bulk of the organelle was shown to accumulate free [cation2+]er up to a steady state in the millimolar range. A theoretical model, based on the existence of multiple ER subcompartments of high and low [Ca2+], that closely mimics the experimental data obtained in HeLa cells during accumulation of either Ca2+ or Sr2+, is presented. Moreover, a few other key problems concerning the ER Ca2+ homeostasis have been addressed with the following conclusions: (a) the changes induced in the ER subcompartments by receptor generation of InsP3 vary depending on their initial [Ca2+]. In the bulk of the system there is a rapid release whereas in the small subcompartments with low [Ca2+] the cation is simultaneously accumulated; (b) stimulation of Ca2+ release by receptor-generated InsP3 is inhibited when the lumenal level is below a threshold, suggesting a regulation by [cation2+]er of the InsP3 receptor activity (such a phenomenon had already been reported, however, but only in subcellular fractions analyzed in vitro); and (c) the maintenance of a relatively constant level of cytosolic [Ca2+], observed when the cells are incubated in Ca2+-free medium, depends on the continuous release of the cation from the ER, with ensuing activation in the plasma membrane of the channels thereby regulated (capacitative influx).
We have measured the [Ca2+] in the endoplasmic reticulum ([Ca2+]er) of intact HeLa cells at both 22 degrees C and 37 degrees C using endoplamsic reticulum-targeted, low Ca2+ affinity aequorin reconstituted with coelenterazine n. Aequorin consumption was much slower at 22 degrees C, and this allowed performing a much longer study of the dynamics of [Ca2+]er. The steady-state [Ca2+]er (500-600 microM) was not modified by the temperature, although both the rates of pumping and leak were decreased at 22 degrees C. The behavior of both [Ca2+]er and cytoplasmic [Ca2+] ([Ca2+]c) after the addition of increasing concentrations of agonists and/or Ca2+-ATPase inhibitors, or following incubation in Ca2+-free medium were compared. We show that agonists induce a fast but relatively small decrease in [Ca2+]er, which is enough to produce a sharp increase in [Ca2+]c. Termination of Ca2+ release is controlled by feedback inhibition of the inositol 1,4,5-trisphosphate receptors by [Ca2+]c, a mechanism that appears to be designed to release the minimum amount of Ca2+ necessary to produced the required [Ca2+]c signal. We also show that Ca2+ release is inhibited progressively when [Ca2+]er decreases below a threshold of about 150 microM, even in the absence of Ca2+ pumping or -Ca2+-c increase. This effect is consistent with a regulation of the inositol 1,4,5-trisphosphate-gated channels by [Ca2+]er.
Previous data have suggested that the large nerve terminals present in the synaptosomal fraction from squid optic lobe are capable of protein synthesis (Crispino et al., 1993a,b). We have further examined this issue by comparing the translation products of synaptosomal and microsomal polysomes. Both preparations programmed an active process of translation, which was completely abolished by their previous treatment with EDTA. After immunoabsorption of the newly synthesized neurofilament (NF) proteins, the labeling ratio of the 60 and 70 kDa NF proteins was found to differ, in agreement with comparable differences obtained with intact synaptosomes. These observations indicate that the set of mRNAs translated by synaptosomes differs from that translated by nerve cell bodies. Hence, because NF proteins are neuron-specific, they support the view that the active synaptosomal polysomes are mostly localized in the large nerve terminals that represent the most abundant neuronal component of the fraction. This hypothesis was confirmed (1) by electron spectroscopic data demonstrating the presence of ribosomes and polysomes within the large nerve endings of the synaptosomal fraction, as well as in the carrot-like nerve endings of the retinal photoreceptors that constitute the only large terminals in the optic lobe, and (2) by light and high resolution autoradiography of synaptosomal samples incubated with [3H]leucine, showing that most labeled proteins are associated with the large nerve endings. This response was abolished by cycloheximide. Taken together, the data provide the first unequivocal demonstration that presynaptic nerve terminals are capable of protein synthesis.
Heparan sulfate proteoglycans (HSPG) have been shown to be involved in the activation of tyrosine kinase receptors by basic fibroblasts growth factor (bFGF), a strong inhibitor of skeletal muscle differentiation. Skeletal muscle fibers contact extracellular matrix (ECM) that surrounds individual fibers (endomysium) and bundles of several fibers (perimysium). Perlecan is a HSPG present in the majority of basement membranes. In this study we evaluated the expression and localization of perlecan during differentiation of C2C12 skeletal muscle cells. C2C12 myoblasts incubated with [35S]Na2SO4 synthesize a HSPG that can be specifically immunoprecipitated with antibodies against murine perlecan. The immunoprecipitated HSPG eluted from a Sepharose CL-4B with a Kav of 0.44. Analysis of the core protein of the HSPG immunoprecipitated from [35S]methionine-labeled C2C12 after treatment with heparitinase revealed two polypeptides of 170 and over 300 kDa. The amount of polypeptides immunoprecipitated decreased with muscle differentiation. Immunocytolocalization studies indicate that perlecan is localized on the myoblast surface and by immunogold staining we have demonstrated that it is associated with patches of incipient extracellular matrix. The expression of perlecan mRNA decreased substantially during skeletal muscle differentiation, in contrast to the increase in transcripts for specific skeletal muscle proteins such as myogenin and creatine kinase. By immunofluorescence microscopy almost no perlecan staining associated with the surface of myotubes was observed. All these results suggests that perlecan, a HSPG that binds myogenic inhibitory bFGF, normally associated with basement membranes in adult tissues is present on the surface of myoblasts and its expression is down regulated during skeletal muscle differentiation.
The combination of accurate translation stages with carefully polished slit blades leads to slits that have many advantages as pinholes for coherent X-ray scattering experiments. The size is adjustable and can be made as small as 0.5 mum. Setting up is easy, while the blade thickness (1 mm tungsten) also makes the slits useful for hard X-rays. A relation between the slit-sample distance and the minimum beam size, together with the corresponding slit size, is derived. This shows that a micrometer-sized beam can be achieved with this type of slits.
Measles virus (MV) enters cells by attachment of the viral hemagglutinin to the major cell surface receptor CD46 (membrane cofactor protein). CD46 is a transmembrane glycoprotein whose ectodomain is largely composed of four conserved modules called short consensus repeats (SCRs). We have previously shown that MV interacts with SCR1 and SCR2 of CD46. (M. Manchester et al. (1995) Proc. Natl. Acad. Sci. USA 92, 2303-2307) Here we report mapping the MV interaction with SCR1 and SCR2 of CD46 using a combination of peptide inhibition and mutagenesis studies. By testing a series of overlapping peptides corresponding to the 126 amino acid SCR1-2 region for inhibition of MV infection, two domains were identified that interacted with MV. One domain was found within SCR1 (amino acids 37-56) and another within SCR2 (amino acids 85-104). These results were confirmed by constructing chimeras with complementary regions from structurally similar, but non-MV-binding, SCRs of decay accelerating factor (DAF; CD55). These results indicate that MV contacts at least two distinct sites within SCR1-2.
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A case of herpes simplex virus (HSV) encephalitis with disseminated primary HSV infection in a renal transplant patient is described. The diagnosis of the disease was achieved by nested polymerase chain reaction (PCR)-DNA in cerebrospinal fluid (CSF). Other diagnostic measures (immunoglobulin [Ig] M and virological cultures both in blood and CSF) were negative. Blood IgG gave a false-positive signal. Although ganciclovir is not the drug of choice, its concomitant administration in our patient as a prophylactic measure against CMV infection may have decreased the usual severity normally expected in this kind of primary HSV infection. The subsequent increase in ganciclovir dose to full therapeutic range, which was implemented before the diagnosis was achieved, led to the disappearance of symptoms. The detection of PCR-DNA in CSF will probably become the diagnostic method of choice. One of its great advantages, in addition to its diagnostic reliability, is that it may obviate the performance of many cerebral biopsies.
We describe a case of primary cardiac lymphoma presenting with chest pain, complete AV block, negative T waves, and infiltration of the basal segments and right free ventricular wall on echocardiography, interpreted initially as hypertrophy. One month later the patient was readmitted with systemic disease and cardiac insufficiency. Furthermore multicentric myocardial infiltration with a nodular mass in the right atrium producing severe tricuspid stenosis was demonstrated. Surgical biopsy was performed and a high grade non-Hodgkin's lymphoma diagnosed. The patient died during the immediate post-operative period without receiving specific chemotherapeutic treatment. Reviewing the published cases, we found that primary cardiac lymphomas are fast growing tumors that infiltrate predominantly the right cavities and have limited therapeutic options.