Biomedical subjects

J M Alonso

Publications and source records attributed to J M Alonso.

At least 37 records · Page 2Linked to original sources

PubMed2001

Construction of complex receptive fields in cat primary visual cortex.

In primary visual cortex, neurons are classified into simple cells and complex cells based on their response properties. Although the role of these two cell types in vision is still unknown, an attractive hypothesis is that simple cells are necessary to construct complex receptive fields. This hierarchical model puts forward two main predictions. First, simple cells should connect monosynaptically to complex cells. Second, complex cells should become silent when simple cells are inactivated. We have recently provided evidence for the first prediction, and here we do the same for the second. In summary, our results suggest that the receptive fields of most layer 2+3 complex cells are generated by a mechanism that requires simple cell inputs.

Animals↗

PubMed2001

[Meningococcal W135 infection epidemics associated with pilgrimage to Mecca in 2000].

OBJECTIVES: On April 3 and 7, 2000, four cases of Neisseria meningitidis serogroup W135 infection were diagnosed in France in Raj pilgrims and their close relatives. Two cases were fatal. Due to the rarity of this strain in France, a strain belonging to a clonal complex implicated in several epidemics in Europe and North America, and it high mortality observed, The French General Direction of Heal issued recommendations on April 8th for rifampicin chemotherapy for all pilgrims and relatives living in their home. The national disease watch (Institut de Veille Sanitaire, InVS) conducted an investigation to describe the epidemic and follow the diffusion of the strain in the population and assess the impact of preventive measures taken as well as need for other specific measures. METHODS: A case was considered to be confirmed when the strain isolated from usually sterile media after March 22 was found to be identical to the epidemic strain (W135, 2a: P1-2.5--clonal complex ET37). A case was considered probable when a pilgrim or in a person in contact with a pilgrim had clinical meningitis (purulent cerebrospinal fluid or purpura fulminans) or when the identified strain was in the W135 serogroup but could not be further identified. A standardized questionnaire developed in collaboration with the European countries concerned by the epidemic was filled out. RESULTS: By November 20, 2000, 25 confirmed and 2 probable cases were identified; 85% of the cases occurred during the first 7 weeks of the epidemic. Mortality was 18%. Patients aged over 50 years accounted for 66% of the cases (6/9) occurring before April 9, 2000 and 17% of the cases (3/18) observed after this data. Four patients had single-joint arthritis. No cluster cases could be identified. Four cases occurred among 19,100 pilgrims (attack rate 21/100,000), 9 among persons living with pilgrims, 7 among subjects in direct contact with pilgrims but not living with them, and 7 among persons who had no identifiable contact with pilgrims. These last 7 cases occurred after the 3rd week of the epidemic. No cases occurred among persons who had taken rifampicin chemoprophylaxis. Eighteen cases occurred after diffusion of the prophylaxis recommendations including 5 in a population directly concerned by the recommendations. CONCLUSIONS: These data suggest that the epidemic strain is not different from other strains in terms of virulence and transmissibility. Eight months after the Raj, the number of cases related to the epidemic remained limited in France. The characteristics of the most recent cases do however suggest an epidemic clone persists in the general population. The Direction of Health recommends vaccination using the quadrivalent A,C,W135,Y vaccine for the 2001 Raj.

Aged↗

PubMed2001

[Clonal spread of Neisseria meningitidis W135].

OBJECTIVES: Efficient surveillance of communicable diseases involves dose collaboration between physicians, epidemiologist and bacteriologists. The characterization of meningococcal infections is a medical emergency due to their lethality and their epidemic behavior. The recent expansion of Neisseria meningitidis of serogroup W135 among pilgrims and their contacts underlines the need of a multidisciplinary procedure of alert. METHODS: Meningococcal strains are usually received by the National Reference Center for Meningococci (CNRM). They are identified and then typed to determine their antigenic formula (serogroup:serotype:serosubtype). For cluster analysis, the CNRM as well as the WHO collaborating center, perform molecular typing of isolated strains. Should an epidemic is suspected, the institut de Veille Sanitaire and the Direction Générale de la Santé are immediately informed. RESULTS: Between the 22th of March and the 20th of November 2000, 27 cases of systemic meningococcal infections due to N. meningitidis of the antigenic formula W135:2a:P1-2.5 were identified. Molecular typing of these strains showed that they were clonal and belonged to the complex ET-37. The dissemination of this clone among pilgrims who were vaccinated against serogroups A and C may suggest the selection of a new variant by an escape alteration in the capsule. However, such strains were detected in France as early as 1994. CONCLUSION: The global spread of N. meningitidis of serogroup W135 belonging to the ET-37 clonal complex should be kept under a close surveillance since epidemics may occur particularly in Africa. New vaccination procedures (quadrivalent vaccines and multivalent conjugate meningococcal vaccines) are therefore needed.

Clone Cells↗

PubMed2001

Rules of connectivity between geniculate cells and simple cells in cat primary visual cortex.

Hundreds of thalamic axons ramify within a column of cat visual cortex; yet each layer 4 neuron receives input from only a fraction of them. We have examined the specificity of these connections by recording simultaneously from layer 4 simple cells and cells in the lateral geniculate nucleus with spatially overlapping receptive fields (n = 221 cell pairs). Because of the precise retinotopic organization of visual cortex, the geniculate axons and simple-cell dendrites of these cell pairs should have overlapped within layer 4. Nevertheless, monosynaptic connections were identified in only 33% of all cases, as estimated by cross-correlation analysis. The visual responses of monosynaptically connected geniculate cells and simple cells were closely related. The probability of connection was greatest when a geniculate center overlapped a strong simple-cell subregion of the same sign (ON or OFF) near the center of the subregion. This probability was further increased when the time courses of the visual responses were similar. In addition, the connections were strongest when the simple-cell subregion and the geniculate center were matched in position, sign, and size. The rules of connectivity between geniculate afferents and simple cells resemble those found for retinal afferents to geniculate cells. The connections along the retinogeniculocortical pathway, therefore, show a precision that goes beyond simple retinotopy to include many other response properties, such as receptive-field sign, timing, subregion strength, and size. This specificity in wiring emphasizes the need for developmental mechanisms (presumably correlation-based) that can select among afferents that differ only slightly in their response properties.

Action Potentials↗

PubMed2001

Phototropin-related NPL1 controls chloroplast relocation induced by blue light.

In photosynthetic cells, chloroplasts migrate towards illuminated sites to optimize photosynthesis and move away from excessively illuminated areas to protect the photosynthetic machinery. Although this movement of chloroplasts in response to light has been known for over a century, the photoreceptor mediating this process has not been identified. The Arabidopsis gene NPL1 (ref. 2) is a paralogue of the NPH1 gene, which encodes phototropin, a photoreceptor for phototropic bending. Here we show that NPL1 is required for chloroplast relocation induced by blue light. A loss-of-function npl1 mutant showed no chloroplast avoidance response in strong blue light, whereas the accumulation of chloroplasts in weak light was normal. These results indicate that NPL1 may function as a photoreceptor mediating chloroplast relocation.

Arabidopsis↗

PubMed2001

An Arabidopsis circadian clock component interacts with both CRY1 and phyB.

Most organisms, from cyanobacteria to mammals, use circadian clocks to coordinate their activities with the natural 24-h light/dark cycle. The clock proteins of Drosophila and mammals exhibit striking homology but do not show similarity with clock proteins found so far from either cyanobacteria or Neurospora. Each of these organisms uses a transcriptionally regulated negative feedback loop in which the messenger RNA levels of the clock components cycle over a 24-h period. Proteins containing PAS domains are invariably found in at least one component of the characterized eukaryotic clocks. Here we describe ADAGIO1 (ADO1), a gene of Arabidopsis thaliana that encodes a protein containing a PAS domain. We found that a loss-of-function ado1 mutant is altered in both gene expression and cotyledon movement in circadian rhythmicity. Under constant white or blue light, the ado1 mutant exhibits a longer period than that of wild-type Arabidopsis seedlings, whereas under red light cotyledon movement and stem elongation are arrhythmic. Both yeast two-hybrid and in vitro binding studies show that there is a physical interaction between ADO1 and the photoreceptors CRY1 and phyB. We propose that ADO1 is an important component of the Arabidopsis circadian system.

Animals↗

PubMed2001

Rapid and stereocontrolled synthesis of racemic and optically pure highly functionalized pyrrolizidine systems via rearrangement of 1,3-dipolar cycloadducts derived from 2-azetidinone-tethered azomethine ylides.

This work describes a convenient procedure for the straightforward preparation of polyfunctionalized enantiopure pyrrolizidine systems. The methodology capitalizes on a HCl(g)-promoted reaction of the 1,3-dipolar cycloadducts derived from 2-azetidinone-tethered azomethine ylides, smoothly affording different types of highly functionalized bi- and tricyclic systems in racemic and optically pure forms. This process involves a selective bond cleavage of the four-membered ring, followed by a rearrangement under the reaction conditions. The synthetic route employed was shown to be compatible with a variety of 4-oxoazetidine-2-carbaldehydes, alpha-amino esters, or dipolarophiles, offering a versatile entry to pyrrolizidine systems.

Journal Article↗

PubMed2001

The ethylene pathway: a paradigm for plant hormone signaling and interaction.

To dissect the web of signals that control plant growth, it is important to understand how the individual components of the pathway are modulated. Ethylene is a plant hormone involved in a large number of developmental processes. Biochemical and genetic approaches have provided a detailed view of the biosynthetic and signal transduction pathways of this hormone in the reference plant Arabidopsis thaliana. The effects of several hormones and of developmental changes on the regulation of the key enzymes of ethylene biosynthesis, ACC synthase and ACC oxidase, serve as a clear example of interaction between signals in the generation of complex responses. We now have a picture of how ethylene is sensed by the ethylene receptors and how the signal is further transduced to the nucleus. Although some of the ethylene receptors show a tissue-specific pattern of expression, little is known about the regulation of the components of the ethylene transduction cascade by other hormones or developmental factors. Once the ethylene signal reaches the nucleus, it activates a transcriptional cascade that results in changes in the expression of a number of genes. We describe some of the results that suggest an interaction at the transcriptional level between ethylene, other hormones, and stress signals.

Animals↗

PubMed2001

Natural antibodies to nematode biotinyl-enzymes in human sera.

Biotinyl-enzymes are conservative molecules present in helminths, as well as in other animals, bacteria and plants. They have recently been found to be antigenic in mice, and a potential source of cross-reactivity among helminths. This study investigated the presence in human sera of antibodies reactive with biotinyl-enzymes from the nematodes Anisakis simplex, Toxocara canis and Ascaris suum. Biotinyl-enzymes from all these nematodes were recognized by IgG1 antibodies in sera from healthy subjects and from Anisakis-free patients infected with other parasites. Interestingly, IgE antibodies reactive with Anisakis simplex biotinyl-enzymes were present in about one third of the sera from Anisakis-free patients infected with other parasites. Our results also demonstrate that the anti-BE IgG1 and IgE antibodies present in the sera of Anisakis-free subjects are cross-reactive among helminths. We conclude that biotinyl-enzymes from nematodes are recognized by natural human antibodies, although Anisakis biotinyl-enzymes do not seem to be the cause of sensitization. Since sera from the Anisakis-free population also present these antibodies, as-yet unidentified factors (dietary components, intestinal inflammation and/or the presence of parasites) may contribute to the induction of anti-BE antibody background.

Adolescent↗

PubMed2001

A simple and reliable procedure for cord blood banking, processing, and freezing: St Louis and Ohio Cord Blood Bank experiences.

BACKGROUND: In UC blood banking, volume and RBC reduction of the collected UC blood allows more efficient long-term storage and decreases infusion-related hemolysis and DMSO toxicity. However, high cell yields are imperative. At the St Louis Cord Blood Bank, we have systematically addressed processing/freezing and have developed a simple processing/freezing procedure. METHOD: The methodology is a modification of the hetastarch sedimentation and volume reduction approach of Rubinstein at the New York Placental Blood Program. Cord blood is mixed with a 1:5 v/v ratio of hetastarch. The product is incubated for 45 min in an inverted position in a refrigerated centrifuge (4 degrees C), and then is spun for 5 min at 50 g. RBC concentrate is drained from the bottom. The volume drained is calculated to remove 80% of RBC. The UC blood unit is then resuspended and spun for 13 min at 420 g. Plasma is expressed from the top. RESULTS: A final product volume of 27 mL (range 16-58 mL) was obtained from an original 50-200 mL of UC blood collected. The average yield of total nucleated cells pre- and post-processing was 90% for the first 4055 UC blood units banked. Pre- and post-processing CFU and CD34 yields were tested in a cohort and were similarly conserved. With a processing time of 3 h for a single cord, this process is time efficient and lends itself well to processing several units at the same time. The technique has been exported to other laboratories with similar yields. DISCUSSION: This simple methodology results in reliable yields and is well suited to larger scale banking.

Blood Banking↗

PubMed2001

Polymorphism of Neisseria meningitidis penA gene associated with reduced susceptibility to penicillin.

We studied polymorphism of penA (which encodes penicillin-binding protein 2) in 13 strains of Neisseria meningitidis susceptible to penicillin (pen(S)) and 12 strains with reduced susceptibility to penicillin (pen(I)). These strains differed in geographical origin. Serological and genetic typing showed that they were highly diverse and belonged to several genetic lineages. Restriction analysis and DNA sequencing of penA showed that all pen(S) strains had the same penA allele regardless of genetic group, whereas pen(I) strains harboured various penA alleles. Transformation with amplicons of penA and genomic DNA from several pen(I) strains conferred the pen(I) phenotype on a pen(S) strain. Thus, reduction in susceptibility to penicillin is directly related to changes in penA and analysis of penA polymorphisms could be used as a reliable tool for characterizing meningococcal strains in terms of their susceptibility to penicillin.

Alleles↗

PubMed2001

Effective combination therapy for invasive pneumococcal pneumonia with ampicillin and intravenous immunoglobulins in a mouse model.

Intranasal immunotherapy for Streptococcus pneumoniae invasive pneumonia with polyvalent immunoglobulins (IVIG) was effective in mice against pneumonia but failed to prevent bacteremia. The combination of subcurative doses of IVIG and of ampicillin was fully protective. Such an approach, successfully applied in the preantibiotic era, offers new perspectives for modern therapies.

Ampicillin↗

PubMed2001

Nonculture prediction of Neisseria meningitidis susceptibility to penicillin.

We developed a nonculture method to predict the susceptibility of Neisseria meningitidis to penicillin G. The penA gene was amplified and submitted to restriction fragment length polymorphism analysis. This approach was first validated with a collection of 75 meningococcal strains of known phenotypes. It was next successfully applied to 29 clinical samples.

Alleles↗

PubMed2001

Circumvention of herd immunity during an outbreak of meningococcal disease could be correlated to escape mutation in the porA gene of Neisseria meningitidis.

Meningococcal strains isolated during an outbreak were shown to belong to the ET-5 complex and to harbor a mutation in the VR2 region of the porA gene. They were less susceptible to the bactericidal effect of normal human serum than was the ET-5 wild-type strain. These results are of concern, as PorA is a potential target in vaccine design.

Disease Outbreaks↗

PubMed2001

Plethysmography for the assessment of pneumococcal pneumonia and passive immunotherapy in a mouse model.

The increasing prevalence of resistance to antibiotics of Streptococcus pneumoniae, the main causative agent of community-acquired bacterial pneumonia, necessitates the development of both new therapeutic strategies and noninvasive methods in order to evaluate their efficacy. The efficacy of passive immunotherapy with human intravenous immunoglobulin (IVIG) or solvent alone, administered intranasally or intravenously, was evaluated in a mouse model of acute pneumonia. Lung bacterial load was also evaluated, using a classical but invasive method, as was respiratory function (minute ventilation, respiratory frequency and tidal volume) using plethysmography, a simple noninvasive method commonly used in inhalation toxicology, but not previously used to assess respiratory infection. Forty-eight hours after infectious challenge, the lung bacterial load was significantly lower in IVIG-treated mice than in untreated mice. At the same time, minute ventilation was significantly lower than reference values for untreated mice (36+/-3 versus 57+/-8 mL.min(-1), p<0.01, and 31+/-2 versus 50+/-5 mL.min(-1), p<0.01 for intranasal and intravenous administration of solvent, respectively) but not in mice treated with IVIG by either route of administration. Plethysmography therefore appears to be a simple and reliable test for the follow-up of acute respiratory infection.

Acute Disease↗

PubMed2001

Contamination of soils with eggs of Toxocara in a subtropical city in Argentina.

A total of 475 soil samples were collected from five public park playgrounds, 17 kindergarten sandpits and 124 housing estates in Resistencia, a medium-sized subtropical-region city in Argentina, and processed by the centrifugal flotation method. Eggs of Toxocara spp. were present in five (3.4%) of the 146 habitats surveyed and in six (1.3%) of the 475 samples examined. Twenty per cent of public parks, 5.9% of kindergarten sandpits and 2.4% of housing estates were contaminated with Toxocara eggs. Depending on the number of samples examined from the three types of habitat, contamination by Toxocara was 0.7% in public park playgrounds, 1.2% in kindergarten sandpits and 1.6% in the housing estates. High prevalences of Ancylostomidae eggs were also found especially in public park playgrounds with a value of 100%, compared with 19.4% found in housing estates and 11.8% in kindergarten samples. These results suggest that in Resistencia, human infections with Toxocara are likely to occur within the limits of housing estates more so than in public parks or open spaces.

Ancylostoma↗

PubMed2000

Synaptic interactions between thalamic inputs to simple cells in cat visual cortex.

We performed experiments in the cat geniculocortical pathway, in vivo, to examine how presynaptic spikes interact to influence the firing of postsynaptic targets. In particular, we asked (1) how do multiple spikes from a single presynaptic neuron interact to influence the firing of a postsynaptic target (homosynaptic interactions), (2) how do spikes from two different presynaptic neurons interact (heterosynaptic interactions), and (3) what is the time course of homosynaptic and heterosynaptic interactions? We found that both homosynaptic and heterosynaptic interactions increase the likelihood of driving a postsynaptic spike, although with different time courses. For two spikes traveling down a single geniculate axon, the second spike is more effective than the first for approximately 15 msec. For two spikes on separate axons, the interaction is faster ( approximately 7 msec duration, approximately 2.5 msec time constant). Thus changes in firing rate are perhaps best relayed by homosynaptic interactions, whereas heterosynaptic interactions may help detect coincident spikes from different thalamic inputs.

Action Potentials↗

PubMed2000

Noise in neurons is message dependent.

Neuronal responses are conspicuously variable. We focus on one particular aspect of that variability: the precision of action potential timing. We show that for common models of noisy spike generation, elementary considerations imply that such variability is a function of the input, and can be made arbitrarily large or small by a suitable choice of inputs. Our considerations are expected to extend to virtually any mechanism of spike generation, and we illustrate them with data from the visual pathway. Thus, a simplification usually made in the application of information theory to neural processing is violated: noise is not independent of the message. However, we also show the existence of error-correcting topologies, which can achieve better timing reliability than their components.

Brain↗