Biomedical subjects

Francisco Muñoz

Publications and source records attributed to Francisco Muñoz.

At least 19 recordsLinked to original sources

PubMed2006

Molecular cloning of multiple forms of the ovine B7-2 (CD86) costimulatory molecule.

To facilitate analysis of the role of costimulatory molecules in the ovine immune system, we cloned and sequenced eight putative alternatively spliced transcripts of the sheep CD86 (B7-2) costimulatory molecule. Using RT-PCR and rapid amplification of cDNA ends (RACE), we cloned the sheep CD86 (B7-2) molecule that encodes eight forms, which differ in the length of the signal peptide, the presence or absence of a transmembrane region and in their cytoplasmic tails. Comparison of the deduced amino acid sequence of the largest ovine CD86 TM form (CD86-2) with the sequence of cattle, pig, human and mouse CD86 indicated that the deduced protein had a higher degree of similarity to cattle (85% of amino acid identity) than to pig (77%), human (59%), and mouse sequence (45% of identity). Our results indicate that mRNA transcripts encoding different CD86 protein forms are expressed in sheep, like in other mammals, and suggest that the expression of this gene may be regulated at the transcriptional or RNA splicing level, which could give rise to tissue-specific expression of CD86. It is possible that, in the sheep, these CD86 mRNA variants could play different regulatory roles in T cell activation.

Alternative Splicing↗

PubMed2005

Dorsolateral prefrontal cortex contribution to abnormalities of the P300 component of the event-related potential in schizophrenia.

Abnormalities of the P300 component of the event-related potential are a common finding in schizophrenia. It seems possible that the dysfunction in the dorsolateral prefrontal (DLPF) region that has been reported in schizophrenia contributes to this finding. To explore this possibility, we calculated the relationship between, on the one hand, P300 latency and amplitude and, on the other hand, the degree of DLPF atrophy (as measured by magnetic resonance imaging) and metabolic activity during an attentional task (as measured by positron emission tomography). Seventeen schizophrenia patients with a brief duration of illness and minimal exposition to treatment and 25 healthy controls were studied. Patients exhibited significantly lower metabolic activity in the DLPF region, but they did not show cortical atrophy. P300 amplitude was also significantly reduced in the schizophrenia patients compared with the controls. Right DLPF region metabolic activity correlated significantly with P300 amplitude. This pattern remained after partialling out the influence of activity in the hippocampus, superior temporal gyrus and parietal lobe. It is therefore suggested that the prefrontal cortex could be implicated in the P300 amplitude reduction in schizophrenia.

Adult↗

PubMed2005

Molecular modeling and chemical reactivity of sanfetrinem and derivatives.

The indiscriminate use of beta-lactams has considerably diminished their efficiency as a result of bacteria developing effective defense mechanisms against them. Recent pharmaceutical research has led to the synthesis of tricyclic beta-lactam antibiotics known as "tricyclic carbapenems" or "trinems". In this work, we studied the chemical reactivity, an essential property for antibiotic action, of trinems and found it to be similar to that of cephalosporins. Also, we elucidated the interaction pattern for sanfetrinem and 4beta-methoxy trinem and compared it to that for classical beta-lactams. The behavior of both trinems was found to be similar to that of penicillin G toward Staphylococcus aureus PC1, and that of cephalothin and imipenem toward Enterobacter cloacae P99.

Anti-Bacterial Agents↗

PubMed2005

Are semantic and syntactic cues inducing the same processes in the identification of word order?

The purpose of this study was to find a common pattern of event-related potential (ERP) fluctuations regardless of the type of information (either semantic or syntactic) determining the presence of a reversed word order. ERPs were recorded while subjects read Spanish transitive sentences in which either semantic or syntactic information determined the actual word order. On the one hand (semantic condition), the order could be reversed by using an inanimate noun in the first noun phrase (NP), together with a verb representing an action that cannot correspond to an inanimate entity. On the other hand (syntactic condition), word order could be manipulated depending on the presence of a preposition preceding the second NP, which confirms the preferred word order, or a determiner, conveying a reversed word order. Interestingly, the inanimate first noun elicited a frontal negativity, which could be interpreted as the detection of an initial difficulty for using that noun as the subject of the sentence. At the point of disambiguation in either condition, a late posterior positivity was observed. The P600/SPS might, therefore, be an indicator of the syntactic processing costs incurred by the variation of word order, reflecting phrase structure reallocation processes common to this operation regardless of the cue used.

Adult↗

PubMed2005

Syntactic expectancy: an event-related potentials study.

Although extensive work has been conducted in order to study expectancies about semantic information, little effort has been dedicated to the study of the influence of expectancies in the processing of forthcoming syntactic information. The present study tries to examine the issue by presenting participants with grammatically correct sentences of two types. In the first type the critical word of the sentence belonged to the most expected word category type on the basis of the previous context (an article following a verb). In the second sentence type, the critical word was an unexpected but correct word category (an article following an adjective) when a verb is highly expected. Event-related potentials (ERPs) were measured to critical words in both sentence types. Brain waves evoked by the correct but syntactically unexpected word revealed the presence of a negativity with a central distribution around 300-500 ms after stimuli onset, an N400, that was absent in the case of syntactically expected words. No differences were present in previous time windows. These results support models that differentiate between the processing of expected and unexpected syntactic structures.

Adult↗

PubMed2005

Molecular modeling of Henry-Michaelis and acyl-enzyme complexes between imipenem and Enterobacter cloacae P99 beta-lactamase.

We report a molecular-mechanics (AMBER*) study on the Henry-Michaelis complex and the corresponding acyl-enzyme adduct formed between imipenem (1), a transient inhibitor of beta-lactamases, and Enterobacter cloacae P99, a class C-beta-lactamase. We have examined the influence of the structural configuration of the functional groups in the substrate on their three-dimensional (3D) arrangement at the active site, which was compared with those adopted by typical penicillins and cephalosporins. Our results confirm that the carboxy group of the antibiotic plays a prominent role in the binding of the substrate to the active site, and that it activates Ser64 through interaction with the phenolic OH group of Tyr150. The binding of imipenem to E. cloacae P99 increases the distance between Tyr150 and Ser64 due to the presence of a hydrophobic Me group in the (R)-1-hydroxyethyl substituent at C(6). This, together with the 3D arrangement of its carboxy group, leads to an interaction with the active site in a manner that hinders H+ exchange between the nucleophile in Ser64 and its basic activator, the phenolic group of Tyr150.

Binding Sites↗

PubMed2005

Inhibition of glycosylation processes: the reaction between pyridoxamine and glucose.

Glycosylation of proteins by glucose produces toxic and immunogenic compounds called 'advanced glycosylation end products' (AGEs), which are the origin of pathological symptoms in various chronic diseases. In this work, a kinetic study of the reaction between glucose (2) and pyridoxamine (1)--a potent inhibitor of AGEs formation both in vivo and in vitro--was conducted. The NH2 group of pyridoxamine was found to react with the C=O group of glucose to form the Schiff base 9 (Scheme 2). Subsequently, the Schiff base gives rise to other products, including compound 3, pyridoxal, pyridoxine, and 4-pyridoxic acid. Compound 3 inhibits the Amadori rearrangement, and prevents the formation of other C=O groups capable of triggering glycosylation processes. Pyridoxal and pyridoxine can also inhibit protein glycosylation via other previously reported mechanisms.

Glucose↗

PubMed2005

Higher-order activity beyond the word level: cortical dynamics of simple transitive sentence comprehension.

Slow electrophysiological effects, which fluctuate throughout the course of a sentence, independent of transient responses to individual words, have been reported. However, this type of activity has scarcely been studied, and with only limited use of electrophysiological information, so that the brain areas in which these variations originate have not been clearly identified. To improve this state of affairs, a principal component analysis and a modern source analysis algorithm (LORETA) were applied to the slow activity underlying transitive sentence reading. Four components explained 97.3% of the variance. Of key interest was a slow variation that occurred throughout the entire sentence but peaked with the appearance of the verb. The main solution for this component was localized in prefrontal and temporal regions presumably involved in semantic sentence processing. This constitutes empirical evidence for cortical activity--related to semantic processes thought to be involved in thematic role assignment--developing throughout the sentence but presenting a conspicuous maximum with the appearance of the verb. This finding also highlights the central role of verb information in the understanding of transitive sentences.

Adult↗

PubMed2005

Are the anterior negativities to grammatical violations indexing working memory?

Anterior negativities obtained when a grammatical rule is violated may reflect highly automatic first-pass parsing processes, the detection of a morphosyntactic mismatch, and/or the inability to assign the incoming word to the current phrase structure. However, for some theorists these negativities rather reflect some aspect of working memory processes. Event-related brain potentials (ERPs) obtained for word category and morphosyntactic violations were directly compared with effects obtained when working memory is particularly demanded (embedding subject- or object-relative clauses), yielding a significant dissociation in terms of topography. Even though, the anterior negativities for grammatical violations vanished when relative clauses were embedded, suggesting that the processes reflected by anterior negativities related to grammatical violations and those related to working memory manipulations, even if different, are placing demands on a common pool of limited resources.

Adolescent↗

PubMed2005

Chronic rupture of the pectoralis major muscle: report of two cases.

Rupture of the pectoralis major muscle is relatively rare. The authors present two cases of chronic rupture in which direct suturing was not possible; reconstruction was possible using a bone-patellar tendon autograft. They conclude that this surgical technique may be useful in some cases of chronic ruptures of the pectoralis major muscle in which direct tendon suturing is impossible.

Adult↗

PubMed2004

An electrophysiological (ERP) component, the recognition potential, in the assessment of brain semantic networks in patients with schizophrenia.

Abnormal activation of semantic networks may be the underlying basis for thought disorder (ThD) in patients with schizophrenia. However, whether this abnormality consists of increased or decreased activation is unclear. Previous behavioral and electrophysiological (N400) data have failed to yield consistent evidence for clarifying this hypothesis. One of the event-related potentials (ERP) components (the recognition potential, RP), presumably reflecting activation of specific semantic networks involved in ThD, has not been used to studies of schizophrenia, and may add additional information to support or refute this hypothesis. In an initial experiment, RP amplitude was reduced in schizophrenic patients, but particularly in those with ThD. In a second experiment, in addition to reduced overall RP amplitude, concrete words were shown to have higher amplitudes than abstract words in both patients and controls, supporting a relative integrity of the lexicon in ThD patients. RP reduction suggests that a fewer number of networks' elements are activated when an incoming word is processed, thus supporting hypoactivation of the semantic networks as the basis for ThD.

Adult↗

PubMed2004

Photo-induced processes in vitamin B6 compounds.

In this work, we applied multi-wavelength stopped-flow spectroscopy (MSFS) to study the chemical equilibria between tautomeric or hydrated forms of various vitamin B6 compounds and the Schiff base formed by epsilon-aminocaproic acid (= 6-aminohexanoic acid) with pyridoxal 5'-phosphate at 25 degrees and variable pH. Since some of these compounds are photosensitive, we analyzed the possible occurrence of any secondary photo-induced processes under the conditions of irradiation in the MSFS equipment (continuous irradiation with light from a 75-W Xe lamp spanning the wavelength range of 200-700 nm). To determine the tautomeric composition of these compounds, the electronic absorption spectra were analyzed by means of log-normal curves. Continuous irradiation of pyridoxamine and pyridoxal 5'-phosphate over the wavelength range of 200-700 nm displaces the chemical equilibrium between the tautomeric or hydrated forms of these compounds. However, the Schiff base of epsilon-aminocaproic acid with pyridoxal 5'-phosphate is insensitive to the radiation used. The photo-induced processes detected in pyridoxamine and pyridoxal 5'-phosphate should be taken into account in examining vitamers by MSFS. In fact, these additional processes should be considered in studying the mechanism of action of vitamin B6-dependent enzymes by the MSFS technique, whenever some free vitamer may be present in solution.

Light↗

PubMed2004

Electrophysiological evidence of an early effect of sentence context in reading.

Recognition Potential is an electrophysiological response of the brain that is sensitive to semantic aspects of stimuli. According to its peak values (about 250ms), Recognition Potential appears as a good candidate to reflect lexical selection processes. Consequently, Recognition Potential might be sensitive to contextual information during reading a sentence. In present study, the standard procedures to improve the visibility of Recognition Potential (Rapid Stream Stimulation paradigm) were used in a task in which sentence context was crucial. A parieto-occipital Recognition Potential was observed to peak about 264ms after stimulus onset, followed by a centro-parietal N400 peaking at about 450ms. Recognition Potential was affected by contextual information though, contrary to N400, presenting larger amplitude to contextually congruous words. These results support the assumption that Recognition Potential may reflect lexical selection processes, representing also evidence of context effects on ERP around 250ms after stimulus onset during sentence reading.

Adult↗

PubMed2004

The recognition potential during sentence presentation: stimulus probability, background stimuli, and SOA.

Recognition potential (RP) is an electrical brain response that has proved its usefulness for studying semantic processing of isolated words, and appears when subjects view meaningful stimuli embedded in a stream of background images at a high rate of presentation: the rapid stream stimulation paradigm (RSS). The present technical study is aimed at testing the validity of this procedure in the study of words within sentences. For this purpose, we varied word and background probability of appearance, the number of background stimuli preceding each word, and stimulus onset asynchrony. Probability did not have significant effects on RP, but it was found that a minimum number of two background stimuli preceding each word and a high rate (250 ms) of presentation are preferable for enhancing RP amplitude. The RSS paradigm would therefore improve the visibility-and, hence, refine the analysis-of a component that can nevertheless be obtained with more standard paradigms, such as rapid serial visual presentation, devoid of interspersed background stimuli.

Adult↗

PubMed2004

Electrophysiological evidence of automatic early semantic processing.

This study investigates the automatic-controlled nature of early semantic processing by means of the Recognition Potential (RP), an event-related potential response that reflects lexical selection processes. For this purpose tasks differing in their processing requirements were used. Half of the participants performed a physical task involving a lower-upper case discrimination judgement (shallow processing requirements), whereas the other half carried out a semantic task, consisting in detecting animal names (deep processing requirements). Stimuli were identical in the two tasks. Reaction time measures revealed that the physical task was easier to perform than the semantic task. However, RP effects elicited by the physical and semantic tasks did not differ in either latency, amplitude, or topographic distribution. Thus, the results from the present study suggest that early semantic processing is automatically triggered whenever a linguistic stimulus enters the language processor.

Adolescent↗

PubMed2004

Long-term olanzapine treatment and p300 parameters in schizophrenia.

The well-known amplitude reduction of the P300 appears to be unaffected by the treatment with classical antipsychotics in schizophrenia, whereas the effects of atypical neuroleptics on this event-related potential are less understood. The study of these changes could help in deciding whether the P300 amplitude reduction in schizophrenia is a trait or state marker of that illness and in better describing the effect of atypical antipsychotics on altered cognitive functions. We present a prospective longitudinal study of P300 amplitude and latency before and after 6 months' treatment with olanzapine in 11 patients with schizophrenia. A healthy control group (n = 30) was also studied. Overall, no significant changes, either in amplitude or in latency as measured at Pz and Fz electrodes, were found when comparing the pre- and postolanzapine conditions, despite the overall improvement in positive and negative symptoms. Nevertheless a direct specific association was observed between a P300 amplitude increase with olanzapine and the improvement in negative symptoms. These data would suggest that P300 amplitude reduction in schizophrenia may be relatively independent from clinical state and treatment, thus constituting a trait marker of schizophrenia. Our data also suggest that, in addition to this, some further changes in P300 amplitude might depend on the clinical state of the patients.

Adult↗

PubMed2003

Role of beta-lactam carboxyl group on binding of penicillins and cephalosporins to class C beta-lactamases.

Molecular models for the Henry Michaelis complexes of Enterobacter cloacae, a class C beta-lactamase, with penicillin G and cephalotin have been constructed by using molecular mechanic calculations, based on the AMBER force field, to examine the molecular differentiation mechanisms between cephalosporins and penicillins in beta-lactamases. Ser318Ala and Thr316Ala mutations in both complexes and Asn346Ala and Thr316Ala/Asn346Ala double mutation in penicillin G complex have also been studied. Results confirm that Thr316, Ser318, and Asn346 play a crucial role in the substrate recognition, via their interactions with one of the oxygens of the antibiotic carboxyl group. Both mutation Ser318Ala and Thr316Ala strongly affect the correct binding of cephalotin to P99, the first mainly by precluding the discriminating salt bridge between carboxyl and serine OH groups, and the second one by the Ser318, Lys315, and Tyr150 spatial rearrangements. On the other hand, Ser318Ala mutation has little effect on penicillin G binding, but the Thr316Ala/Asn346Ala double mutation causes the departure of the antibiotic from the oxyanion hole. Molecular dynamic simulations allow us to interpret the experimental results of some class C and A beta-lactamases.

Amino Acid Substitution↗

PubMed2002

The recognition potential and repetition effects.

The recognition potential (RP) is an electrical brain response peaking at 250 ms that appears when subjects view meaningful stimuli. Previous RP research was conducted in experimental conditions in which repetition effects could not be totally ruled out as influencing the generation of the RP response. The present study aims to elucidate whether repetition effects affect the topography and waveform of this component. For this purpose semantically correct, orthographically correct, strings of random letters, control and background stimuli were presented to 20 subjects following the rapid stream stimulation procedure and without repetition of any test stimulus. As previously, the RP showed its maximal amplitude at the PO7 electrode. It showed sensitivity to all levels of lexical processing, its response being maximal for semantically correct stimuli, and its topographical distribution was similar for all types of stimulus. Direct statistical comparisons with the data of a previous study where repetition effects could not be disregarded were performed, confirming the similarity between the results obtained in both experiments. The neural generators of the RP were placed again, as in previous studies, within the lingual gyrus. Although repetition effects have been reported to affect other semantic-related components such as the N400, they do not seem to affect either the topography or the waveform of the RP.

Adult↗