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A Alonso

Publications and source records attributed to A Alonso.

At least 199 records · Page 11Linked to original sources
PubMed1998

Network analyses of Y-chromosomal types in Europe, northern Africa, and western Asia reveal specific patterns of geographic distribution.

In a study of 908 males from Europe, northern Africa, and western Asia, the variation of four Y-linked dinucleotide microsatellites was analyzed within three "frames" that are defined by mutations that are nonrecurrent, or nearly so. The rapid generation and extinction of new dinucleotide length variants causes the haplotypes within each lineage to diverge from one another. We constructed networks of "adjacent" haplotypes within each frame, by assuming changes of a single dinucleotide unit. Two small and six large networks were obtained, the latter including 94.9% of the sampled Y chromosomes. We show that the phenetic relationships among haplotypes, represented as a network, result largely from common descent and subsequent molecular radiation. The grouping of haplotypes of the same network thus fits an evolutionarily relevant criterion. Notably, this method allows the total diversity within a sample to be partitioned. Networks can be considered optimal markers for population studies, because reliable frequency estimates can be obtained in small samples. We present synthetic maps describing the incidence of different Y-chromosomal lineages in the extant human populations of the surveyed areas. Dinucleotide diversity also was used to infer time intervals for the coalescence of each network.

Africa, Northern↗
PubMed1998

Noise from voltage-gated ion channels may influence neuronal dynamics in the entorhinal cortex.

Neurons of the superficial medial entorhinal cortex (MEC), which deliver neocortical input to the hippocampus, exhibit intrinsic, subthreshold oscillations with slow dynamics. These intrinsic oscillations, driven by a persistent Na+ current and a slow outward current, may help to generate the theta rhythm, a slow rhythm that plays an important role in spatial and declarative learning. Here we show that the number of persistent Na+ channels underlying subthreshold oscillations is relatively small (<10(4)) and use a physiologically based stochastic model to argue that the random behavior of these channels may contribute crucially to cellular-level responses. In acutely isolated MEC neurons under voltage clamp, the mean and variance of the persistent Na+ current were used to estimate the single channel conductance and voltage-dependent probability of opening. A hybrid stochastic-deterministic model was built by using voltage-clamp descriptions of the persistent and fast-inactivating Na+ conductances, along with the fast and slow K+ conductances. All voltage-dependent conductances were represented with nonlinear ordinary differential equations, with the exception of the persistent Na+ conductance, which was represented as a population of stochastic ion channels. The model predicts that the probabilistic nature of Na+ channels increases the cell's repertoire of qualitative behaviors; although deterministic models at a particular point in parameter space can generate either subthreshold oscillations or phase-locked spikes (but rarely both), models with an appropriate level of channel noise can replicate physiological behavior by generating both patterns of electrical activity for a single set of parameters. Channel noise may contribute to higher order interspike interval statistics seen in vitro with DC current stimulation. Models with channel noise show evidence of spike clustering seen in brain slice experiments, although the effect is apparently not as prominent as seen in experimental results. Channel noise may contribute to cellular responses in vivo as well; the stochastic system has enhanced sensitivity to small periodic stimuli in a form of stochastic resonance that is novel (in that the relevant noise source is intrinsic and voltage-dependent) and potentially physiologically relevant. Although based on a simple model that does not include all known membrane mechanisms of MEC stellate cells, these results nevertheless imply that the stochastic nature of small collections of molecules may have important effects at the cellular and network levels.

Animals↗
PubMed1998

Clinical evaluation of a new generation membrane oxygenator: a prospective randomized study.

A new generation hollow-fibre membrane oxygenator (Spiral Gold) has been introduced by Baxter Healthcare (Irvine, CA, USA). The purpose of this study was to evaluate the operational performance of this device under clinical conditions and to compare it to the Univox Gold membrane oxygenator. Following institutional review board approval, and the obtainment of informed consent, 26 patients undergoing coronary artery bypass grafting were randomly assigned to either a Spiral Gold (Spiral) (n = 13) or Univox Gold (Univox) (n = 13) group. Study parameters were grouped into the following categories: haematological, haemodynamic, oxygenator performance and perioperative outcomes. All patients received identical surgical, anaesthesia and postoperative care. There were no statistically significant differences in either preoperative or operative parameters between groups. During cardiopulmonary bypass, the Spiral group had a significantly lower pressure drop (26.9 +/- 8.2 vs 46.7 +/- 16.2 mmHg, p < 0.001). The Spiral group had significantly lower plasma free haemoglobin levels during all time periods of CPB compared to the Univox group. Heat exchange coefficients were higher during the rewarming period in the Spiral patients (0.59 +/- 0.28) compared to the Univox group (0.36 +/- 0.19), p = 0.06. There were no differences in oxygen transfer between groups, but ventilation gas sweep rates and FiO2 levels were statistically lower in the Spiral group at two of the three sampling time periods. The ratio of ventilating gas sweep rate to blood flow rate was lower in the Spiral group (0.56 +/- 0.12) compared to the Univox group (0.74 +/- 0.23), p < 0.03. The Spiral Gold oxygenator had superior oxygen transfer efficiency and lower haemolysis rates than the Univox Gold oxygenator.

Adult↗
PubMed1998

Clinical tests for ankle syndesmosis injury: reliability and prediction of return to function.

Despite the severity of ankle syndesmosis injuries, it has been argued that they are relatively poorly detected. This study investigated the interrater reliability of four orthopaedic tests for ankle syndesmosis injury and assessed their ability to predict the extended recovery times that have been reported as a consequence of this injury. Nine physiotherapists, working in random pairings, examined 53 subjects, all receiving treatment for ankle injury at two private clinics. Each subject was tested by two physiotherapists who independently performed the palpation test, external rotation test, squeeze test, and dorsiflexion-compression test. Kappa coefficient testing indicated that the external rotation test had the best interrater reliability (kappa = 0.75). The squeeze test was found to have moderate reliability (kappa = 0.50), and the palpation and dorsiflexion-compression tests both had only fair reliability (kappa = 0.36). The degree of pair-wise association between the results of the four tests was low (phi < or = 0.30 for all test combinations), suggesting that if all four tests were performed on the same subject, it was not likely that they would achieve similar results. Follow-up interviews were conducted to determine the time taken for subjects to walk 10 m without pain and, for sports injuries, the time taken to return to training and then to competition. For each test, Mann-Whitney U values showed no significant difference between the recovery times of subjects with positive or negative test results, although subjects with recovery times markedly longer than normal were detected by three of the four tests. When an either/or combination of the external rotation and dorsiflexion-compression tests was considered, subjects with a positive test result took significantly longer to return to playing sports.

Adolescent↗
PubMed1998

Mechanisms of cell signaling in immune-mediated inflammation.

Deposition of immune complexes in tissues is the pathogenic mechanism underlying tissue injury in a number of diverse clinical conditions affecting the skin, joints, blood vessels and renal glomeruli. Initial approaches to the understanding of these conditions have stressed the roles of both the activation of the complement system and the accumulation of polymorphonuclear leukocytes as the main molecular and cellular mechanisms explaining the sequence of events leading to tissue damage. Recent findings on (i) the molecular biology of the leukocyte chemoattractants, (ii) the chemical structure and function of receptors for the Fc portion of the antibody molecule and (iii) the signaling events coupled to the engagement of these receptors have led to an understanding of the biochemical events involved in immune-complex injury and have provided a promising avenue for the development of therapeutic approaches. This review will focus on our current understanding of signal transduction events in the effector phase of immune-complex-mediated tissue injury.

Anaphylatoxins↗
PubMed1998

[Intestinal obstruction and necrotizing thyroiditis secondary to Pneumocystis carinii infection in a seropositive hemophiliac patient seropositive for human immunodeficiency virus].

We report a case of bowel infection by Pneumocystis carinii (PC) that presented as an acute obstruction accompanied by intestinal hemorrhage (melena) in a HIV seropositive hemophilic patient. Laparotomy followed by resection of two plaque-like jejunal tumors was performed, and intravenous therapy with pentamidine was initiated. No other organ was found to be affected by PC (not even the lung), with the exception of the thyroid gland. To our knowledge, this is the first reported case in which acute intestinal obstruction was the presenting symptom of extrapulmonary pneumocystosis.

AIDS-Related Opportunistic Infections↗
PubMed1998

[HCV and HBV prevalence in hemodialyzed pediatric patients. Multicenter study].

Hemodialized pediatric patients are a risk population for the hepatitis B and C virus infection. The aim of this paper was to study the serum prevalence of HBV and HCV infection in hemodialized children. We study 61 pediatric patients at hemodialisis, 12 on renal transplant, range between 2 and 20 years old (mean: 12.9 years), 23 male and 38 female. The specific anti-HCV IgC were measured by enzyme immunoassay (ELISA Abbott) and confirmed by LIA-TEK (Organon). The anti-HBV were measured by ELISA Abbott and transaminases by cinetic method (ASAT: 29 UI/L and ALT: 33 UI/L). The 19.7% of studied children were HCV (+) and 29.5% were HBV (+), 38.9% of them were HbsAg (+) and 50% anti-HBs (+). The HCV and HBV infection was more elevated in relation to the transfusion number and the hemodilisis time. The elevation of ALT/ASAT activity isn't a right infection index for HCV and HBV in this children.

Adolescent↗
PubMed1998

[Amyotrophic neuralgia: review of 37 cases].

INTRODUCTION: Amyotrophic neuralgia is characterized by pain of acute or subacute onset, accompanied by weakness and occasionally by atrophy of the brachial muscles, of unknown origin. We present our experience over the past 20 years. PATIENTS AND METHODS: We made a retrospective review of 37 patients with the above diagnosis, following the criteria of other series of such cases published in the literature. RESULTS: Twenty four of the patients were men and thirteen were women. The average age was 38 (11 to 71). A relevant clinical history was recorded in 9 cases; infection (5), surgery (4), remote trauma (3) and vaccination (1). There was a painful onset of the condition in 32 patients; objective weakness of the superior brachial plexus (30), inferior (5) or both (2). Atrophy was present in 23 and hypoaesthesia in 13. Two patients had fasciculations and 9 had hyperreflexia. In all patients electromyographic studies showed a neurogenic pattern of denervation of the muscles clinically affected. The severity of the condition was divided into mild (18), moderate (16) and intense (3). Prognosis was good in 24 and sequelae remained in 11. There were 2 bilateral cases and 2 relapses but no familial cases. CONCLUSIONS: There was a ratio of men/women of 1.8:1 and onset usually when the patient was in his forties. Mild infection, surgery, remote trauma and vaccination were the commonest clinical factors. Onset was painful in 85%. Muscular weakness was predominantly in the superior brachial plexus (85%), followed by atrophy in 62%. There was hypoaesthesia in a third of the patients. Most cases were mild (50%) and made a complete recovery (70%). Our findings are similar to those described in most series in the literature.

Acute Disease↗
PubMed1997

Enhancement of EGF- and PMA-mediated MAP kinase activation in cells expressing the human papillomavirus type 16 E5 protein.

In this report we demonstrate that cells expressing the human papillomavirus type 16 E5 open reading frame (HPV16-E5) show a greatly enhanced transcription of the immediate early genes after EGF or PMA treatment compared to control cells. This enhancement is due to amplification of the signal transduction pathways in response to growth factors or phorbol esters. Upon short-time EGF treatment of the E5-expressing cells we observed an increase in the activation of EGF receptors, resulting in a stronger activation of MAP kinases ERK1/2 compared to control-transfected cells. We also observed that in E5-expressing cells, treatment with PMA results in an increase in membrane-associated PKC activity, and a superactivation of the ERK1/2 MAP kinases. This superactivation is PKC-dependent, since pretreatment of the cells with the PKC inhibitor Ro 31-8220 inhibits MAP kinase activation and early gene transcription almost completely. Furthermore, treatment with genistein strongly reduces the PMA-mediated superactivation of ERK1/2 kinases, demonstrating a PKC-mediated, tyrosine kinase-dependent pathway in the superinduction of MAP kinase activation. Thus, HPV16-E5 effects superactivation of MAP kinases over at least two different pathways, a PKC-mediated, and another, receptor tyrosine-kinase mediated, PKC-independent one.

3T3 Cells↗
PubMed1997

Muscarinic induction of synchronous population activity in the entorhinal cortex.

Oscillation and synchronization of neural activity is important in normal brain function but is also relevant to epileptogenesis. One of the most frequent forms of epilepsy originates in temporal lobe circuitry of which the entorhinal cortex (EC) is crucial. Because muscarinic receptor activation promotes oscillatory dynamics in EC neurons, we investigated in a brain slice preparation the effects of carbachol (CCh) on oscillatory population activity in the EC. We found that CCh produced epileptiform activity in EC, which according to field profile and current source density analysis was usually driven by layer V. In addition, localized CCh application and surgical isolation experiments demonstrated that EC layer II, but not layer III, can also independently generate synchronous population activity. Intracellular recordings from EC principal cells during epileptiform activity demonstrated large-amplitude, synaptically driven depolarizing events and bursts of action potentials synchronized to the field spikes. In layer II neurons, the depolarizing events had a multiphasic reversal potential that suggested concurrent glutamatergic and GABAergic synaptic input. Interestingly, although the epileptiform activity required activation of AMPA but not NMDA receptors, small-amplitude field spikes persisted during block of fast excitatory neurotransmission. These field spikes were correlated to large-amplitude IPSPs in layer II neurons, and both activities were abolished by GABAA-receptor antagonism. Thus, in response to muscarinic activation, pools of EC interneurons discharge synchronously by a mechanism not necessarily involving principal cell activation. Given the differential projection pattern of EC layers V and II toward the neocortex and hippocampus, respectively, their robust epileptogenic character may be of major importance in temporal lobe epilepsy.

Animals↗
PubMed1997

Stimulation of Fc gamma receptors in rat peritoneal macrophages induces the expression of nitric oxide synthase and chemokines by mechanisms showing different sensitivities to antioxidants and nitric oxide donors.

The induction of nitric oxide (NO) production and the expression of cytokine-induced neutrophil chemoattractant (CINC-1) were studied in rat peritoneal adherent cells stimulated with insoluble immune complexes containing rabbit IgG Ab and OVA as the cognate Ag (IC). Incubation with IC at concentrations as low as 10 microg/ml induced NO production and the expression of inducible NO synthase (iNOS) protein. This was accompanied by the expression of CINC-1 mRNA and the activation of nuclear factor-kappaB (NF-kappaB). However, the expression of iNOS and CINC-1 mRNA induced by IC showed a different temporal pattern and a different sensitivity to both the antioxidant agent pyrrolidine dithiocarbamate (PDTC) and modulation by NO itself. Whereas iNOS mRNA and protein expression were blunted by PDTC and NO-generating compounds, CINC-1 mRNA expression was either enhanced or not affected by PDTC and NO donors. The time course of NF-kappaB activation was parallel to that of iNOS induction and was influenced in the same sense as iNOS induction by antioxidants, NO donors, the protease inhibitor N-tosyl phenylalanine chloromethyl ketone, and inhibitors of protein tyrosine phosphorylation reactions. These data indicate the existence in rat macrophages of a signaling mechanism triggered by Fc gammaR occupancy that leads to nuclear signaling, is initiated by protein tyrosine phosphorylation reactions, and shows specific sensitivities to antioxidants and NO. Whereas trans-activation of the iNOS gene can be fully explained by the stimulation of NF-kappaB, induction of CINC-1 mRNA expression seems influenced by additional regulatory elements.

Animals↗
PubMed1997

Poly(ethylene glycol)-lipid conjugates inhibit phospholipase C-induced lipid hydrolysis, liposome aggregation and fusion through independent mechanisms.

Poly(ethylene glycol)-phosphatidylethanolamine (PEG-PE) conjugates have been introduced in liposomal compositions. The resulting large unilamellar vesicles were subjected to the action of phospholipase C. Enzyme-promoted vesicle aggregation and fusion were assayed in liposomes containing various proportions of PEG-PE. At PEG-PE concentrations above 1 mol% the rate of phospholipid hydrolysis decreases, perhaps because the PEG moiety hinders the enzyme from reaching the membrane surface. At concentrations above 0.1 mol% vesicle aggregation occurs at a slower rate, presumably because of the repulsive barrier properties or surface-grafted PEG. Lipid mixing decreases in parallel with vesicle aggregation. Finally, liposomal fusion rates measured as mixing of vesicle aqueous contents are decreased at or even below 0.1 mol%. The latter inhibition is due, apart from the reduced rates of lipid hydrolysis, vesicle aggregation and lipid mixing, to a PEG-PE-based stabilization of the lipid bilayer structure. Thus the observed low rates of contents mixing arise from three combined and independent inhibitory effects of PEG-PE.

Hydrolysis↗
PubMed1997

Cytosolic phospholipase A2 is coupled to muscarinic receptors in the human astrocytoma cell line 1321N1: characterization of the transducing mechanism.

The cholinergic agonist carbachol induced the release of arachidonic acid in the 1321N1 astrocytoma cell line, and this was blocked by atropine, suggesting the involvement of muscarinic receptors. To assess the mechanisms of signalling involved in the response to carbachol, a set of compounds characterized by eliciting responses through different mechanisms was tested. A combination of 4beta-phorbol 12beta-myristate 13alpha-acetate and thapsigargin, an inhibitor of endomembrane Ca2+-ATPase that induces a prolonged elevation of cytosolic Ca2+ concentration, induced an optimal response, suggesting at first glance that both protein kinase C (PKC) and Ca2+ mobilization were involved in the response. This was consistent with the observation that carbachol elicited Ca2+ mobilization and PKC-dependent phosphorylation of cytosolic phospholipase A2 (cPLA2; phosphatide sn-2-acylhydrolase, EC 3.1.1.4) as measured by a decrease in electrophoretic mobility. Nevertheless, the release of arachidonate induced by carbachol was unaltered in media containing decreased concentrations of Ca2+ or in the presence of neomycin, a potent inhibitor of phospholipase C which blocks phosphoinositide turnover and Ca2+ mobilization. Guanosine 5'-[gamma-thio]triphosphate added to the cell-free homogenate induced both [3H]arachidonate release and cPLA2 translocation to the cell membrane fraction in the absence of Ca2+, thus suggesting the existence of an alternative mechanism of cPLA2 translocation dependent on G-proteins and independent of Ca2+ mobilization. From the combination of experiments utilizing biochemical and immunological tools the involvement of cPLA2 was ascertained. In summary, these data indicate the existence in the astrocytoma cell line 1321N1 of a pathway involving the cPLA2 which couples the release of arachidonate to the occupancy of receptors for a neurotransmitter, requires PKC activity and G-proteins and might operate in the absence of Ca2+ mobilization.

Arachidonic Acid↗
PubMed1997

Delineation of a duplication map of chromosome 3q: a new case confirms the exclusion of 3q25-q26.2 from the duplication 3q syndrome critical region.

We report on the clinical, cytogenetic, and molecular characterization of a propositus and his mother with a duplication of 3q25-q26, minor anomalies, and mental retardation. The duplication, detected by cytogenetic analysis, was confirmed and delineated by comparative genomic hybridization and fluorescence in situ hybridization using probes previously mapped to the region. Comparison of the mapping data obtained in these patients and those obtained in patients that present with a typical dup(3q) syndrome phenotype shows that the segment duplicated in these patients lies proximally to the reported dup(3q) syndrome critical region, thus explaining the absence in our patients of the characteristic phenotype of dup(3q) syndrome patients. Accumulation of mapping data in patients with segmental duplications of 3q will eventually allow us to build a duplication map of the region and a genotype-phenotype correlation.

Adolescent↗