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Biomedical subjects

C Garcia

Publications and source records attributed to C Garcia.

At least 109 records · Page 6Linked to original sources
PubMed1998

Pseudotumor cerebri: an unusual complication of brachiocephalic vein thrombosis associated with hemodialysis catheters.

We report a case of pseudotumor cerebri (PC) in a maintenance hemodialysis patient that was associated with thrombosis of the right and left brachiocephalic veins caused by repeated subclavian and jugular vein catheterizations. Symptoms and signs of PC appeared when a right forearm Gortex graft was inserted. PC secondary to intracranial venous outflow obstruction is an important diagnostic consideration for hemodialysis patients with headache, visual disturbance, and papilledema.

Aged↗
PubMed1998

Allelic inclusion of T cell receptor alpha genes poses an autoimmune hazard due to low-level expression of autospecific receptors.

Organ-specific autoimmune disease can be caused by alphabeta T cells that have escaped self-tolerance induction. Here we show that one of the causes of escape from self-tolerance is the coexpression of two different T cell receptors by the same cell, which can occur in up to 30% of all T cells in normal mice and can lead to low-level surface expression of an autospecific TCR. We found that double receptor-expressing T cells can escape tolerance even to ubiquitously expressed antigens but can nevertheless induce autoimmune diabetes when the relevant protein is expressed in pancreatic tissue. Such diabetogenic T cells are absent, however, among T cells expressing the autospecific TCR as the sole receptor.

Alleles↗
PubMed1998

Probing immunoglobulin gene hypermutation with microsatellites suggests a nonreplicative short patch DNA synthesis process.

As the rate of Ig gene hypermutation approximates the level of nucleotide discrimination of DNA polymerases (10(-3) to 10(-4)), a local inhibition of proofreading and mismatch repair during semiconservative replication could generate the mutations introduced by the process. To address this question, we have constructed transgenic mice that carry a hypermutation substrate containing a "polymerase slippage trap": an Ig gene with a mono or dinucleotide tract inserted in its V region. The low amount of slippage events as compared to the number of mutations, the absence of transient misalignment mutations at the border of the repeats, and the dissociation between the amount of frameshifts and mutations when the transgene is put on mismatch repair-deficient genetic backgrounds, suggest that Ig gene hypermutation occurs by an error-prone short patch DNA synthesis taking place outside global DNA replication.

Animals↗
PubMed1998

Molecular characterization of the putative T-cell receptor cavity of the superantigen staphylococcal enterotoxin B.

A number of investigators have utilized a variety of methods to identify the structural basis for the interaction of superantigens with the T-cell receptor beta-chain. The previous studies strongly suggest that a region of the toxin near residues N23, Y61, Y91 and D209 is important for this binding activity. Examination of crystal structure data shows that these residues line the rim of one side of a shallow cavity in the toxin. In an attempt further to define the face of the staphylococcal enterotoxin B (SEB) molecule involved in the interaction with the beta-chain, we have employed a polymerase chain reaction (PCR)-based, site-specific mutagenesis method to generate amino acid substitutions of residues on the opposite side of this putative T-cell receptor interaction cavity. Our results show that Y175 and N179 appear to be involved in the function of this superantigen, since each of several substitutions at this position exhibits a significantly reduced ability to induce T-cell proliferation. At the same time, mutation of the proximal Y186 does not alter the superantigen activity of SEB. Binding analysis of these mutants shows that class II binding activity is not significantly altered. Analysis of the responding T cells shows that the mutant toxins maintain T-cell receptor V beta selectivity. However, responses of T cells bearing the V beta 8.1 allele appear to be particularly diminished. When viewed in the context of other results reported in the literature, our results suggest that the T-cell receptor interaction site involves SEB residues which ring both the Y175/N179-side and the N23-side of a cavity on one side of the toxin molecule.

Alleles↗
PubMed1998

Proliferation, migration and differentiation of neuronal progenitor cells in the adult mouse subventricular zone surgically separated from its olfactory bulb.

The subventricular zone of the adult mammalian forebrain contains progenitor cells that, by migrating along a restricted pathway called the 'rostral migratory stream' (RMS), add new neurons to the olfactory bulb throughout life. To determine the influence of the olfactory bulb on the development of these progenitor cells, we performed lesions that interrupt this pathway and separate the olfactory bulb from the rest of the forebrain. By labelling cells born at several survival times after the lesions with the thymidine analogue bromodeoxyuridine (BrdU), we found that disconnection from the bulb influences the rate of BrdU incorporation by the progenitor cells. The number of labelled cells in lesioned mice was almost half that found in control mice. In the disconnected migratory pathway, the number of neurons expressing calretinin was increased indicating that neuronal differentiation was enhanced: newly born neurons occurred within and around the RMS, most of them expressed calretinin and left the pathway starting about 2 weeks after the lesion. Thereafter, these neurons preserving their phenotype, spread for long distances, and accumulated ectopically in dorsal regions of the anterior olfactory nucleus and the frontal cortex. Finally, transplantation of adult subventricular cells into the lesioned pathway showed that the lesion neither prevents neuronal migration nor alters its direction. Thus, although the olfactory bulb appears to regulate the pace of the developmental processes, its disconnection does not prevent the proliferation, migration and phenotypic acquisition of newly generated bulbar interneurons that, since they cannot reach their terminal domains, populate some precise regions of the lesioned adult forebrain.

Age Factors↗
PubMed1998

Effects of psychosocial support during labour and childbirth on breastfeeding, medical interventions, and mothers' wellbeing in a Mexican public hospital: a randomised clinical trial.

OBJECT: To evaluate the effects of psychosocial support during labour, delivery and the immediate postpartum period provided by a female companion (doula). DESIGN: The effects of the intervention were assessed by means of a randomised clinical trial. Social support by a doula was provided to women in the intervention group, while women in the control arm received routine care. SETTING: A large social security hospital in Mexico City. PARTICIPANTS: Seven hundred and twenty-four women with a single fetus, no previous vaginal delivery, < 6 cm of cervical dilatation, and no indications for an elective caesarean section were randomly assigned to be accompanied by a doula, or to receive routine care. OUTCOME MEASURES: Breastfeeding practices, duration of labour, medical interventions, mother's emotional conditions, and newborn's health. METHODS: Blinded interviewers obtained data from the clinical records, during encounters with women in the immediate postpartum period, and at their homes 40 days after birth. Relative risks and confidence intervals were estimated for all relevant outcomes. RESULTS: The frequency of exclusive breastfeeding one month after birth was significantly higher in the intervention group (RR 1.64; I-C: 1.01-2.64), as were the behaviours that promote breastfeeding. However, the programme did not achieve a significant effect on full breastfeeding. More women in the intervention group perceived a high degree of control over the delivery experience, and the duration of labour was shorter than in the control group (4.56 hours vs 5.58 hours; RR 1.07 CI (95%) = 1.52 to -0.51). There were no effects either on medical interventions, mothers' anxiety, self-esteem, perception of pain and satisfaction, or in newborns' conditions. CONCLUSIONS: Psychosocial support by doulas had a positive effect on breastfeeding and duration of labour. It had a more limited impact on medical interventions, perhaps because of the strict routine in hospital procedures, the cultural background of the women, the short duration of the intervention, and the profile of the doulas. It is important to include psychosocial support as a component of breastfeeding promotion strategies.

Anxiety↗
PubMed1998

Crucial function of the pre-T-cell receptor (TCR) in TCR beta selection, TCR beta allelic exclusion and alpha beta versus gamma delta lineage commitment.

The analysis of T-cell receptor (TCR) beta selection, TCR beta allelic exclusion and TCR beta rearrangement in gamma delta T cells from normal and pre-TCR-deficient mice has shown that the pre-TCR has a crucial role in T-lymphocyte development: The pre-TCR is by far the most effective receptor that generates large numbers of CD4+8+ T cells with productive TCR beta rearrangements. In the absence of the pre-TCR, TCR beta rearrangement proceeds in developing cells irrespective of whether they already contain a productive TCR beta gene. The pre-TCR directs developing T cells to the alpha beta lineage because gamma delta T cells from pT alpha-/- mice proceed much further in TCR beta rearrangement than gamma delta T cells from wild-type mice. It is argued that the pre-TCR commits developing T cells to the alpha beta lineage by an instructive mechanism, which has largely replaced an evolutionarily more ancient mechanism that involves stochastic alpha beta lineage commitment.

Alleles↗
PubMed1998

Integrating the patient's perspective: patient pathway development across the enterprise.

Two academic medical centers in a newly integrated structure joined to understand better their patients' experience with care processes and to promote increased patient involvement in the plan of care. Through a team approach, a patient pathway was developed using graphic and text elements to illustrate the normal sequence of critical activities and care processes for established clinical pathways at these medical centers. A focus group was held to achieve a higher level of patient input into care coordination issues. Through the integration of the patient's voice into the plan of care, priorities for improvement can be identified.

Academic Medical Centers↗
PubMed1998

Marginal microleakage around enamel and cementum surfaces of two compomers.

The purpose of this study was to evaluate the marginal microleakage of two compomers, placed in enamel and cementum. The buccal and lingual surfaces of twenty human premolar teeth were used. Materials used were Dyract and Compoglass. Teeth were randomly divided into 4 groups of 5 teeth each. Materials were handled according to the instructions of the manufacturer. Class V cavities were prepared with enamel and cementum margins. The groups with etched surfaces was done using 37% phosphoric acid. Two percent fuchsin was used for microleakage study. Results were evaluated using an analysis of ANOVA. These showed that microleakage in enamel was significantly less than in cementum. No significant differences in microleakage were seen between the two materials or between etched and unetched surfaces.

Acid Etching, Dental↗
PubMed1998

Photoaddition to DNA by nonintercalated chlorpromazine molecules.

Chlorpromazine (CPZ) forms photoadducts with DNA and photosensitizes DNA strand breaks. These reactions may be responsible for the reported photomutagenicity of CPZ and for the well-known cutaneous and ocular phototoxicity associated with this drug. We have investigated whether CPZ molecules that are intercalated between base pairs in double-stranded (ds) DNA are the absorbing species for the photoaddition reaction. Quenching of CPZ fluorescence by ds-DNA gave nonlinear Stern-Volmer plots, indicating that more than one type of complex is formed. Linear dichroism spectra of CPZ in the presence of ds-DNA showed a minimum at 345 nm, indicating that the absorption maxima of intercalation complex(es) are red-shifted compared to the absorption maximum of free CPZ at 307 nm. The sum of the absorption of all CPZ complexes with ds-DNA, obtained from dialysis experiments, was broadened and maximized at about 315 nm, indicating that complexes not involving intercalation dominate the absorption spectrum at lambda < 350 nm. The wavelength dependence for covalent binding of CPZ to DNA was determined by irradiating 3H-CPZ in the presence of ds-DNA at 310, 322, 334, 346, 358 and 370 nm. The resulting spectrum correlated closely with the absorption spectrum of nonintercalated CPZ rather than with the spectrum of intercalated CPZ, indicating that the latter species is not the chromophore for the photoaddition reaction.

Chlorpromazine↗
PubMed1997

Heteronuclear NMR studies of E. coli translation initiation factor IF3. Evidence that the inter-domain region is disordered in solution.

Initiation factor IF3 from Escherichia coli plays a critical role in the selection of the correct initiation codon. This protein is composed of two domains, connected by a lysin-rich hydrophilic linker. The conformation of native IF3 was investigated by heteronuclear NMR spectroscopy. The two domains are independent and show little or no interaction. Heteronuclear relaxation studies of a sample selectively labelled on lysine residues demonstrates that the inter-domain linker is highly flexible, exhibiting increased 15N T2 values and negative 1H[15N] nuclear Overhause effects over a length of at least eight residues. Analysis of the rotational correlation times further shows that the motions of the two domains are most likely uncorrelated. The inter-domain linker thus displays almost totally unrestricted motions. Accordingly, the amide protons in the central region are shown to be in fast exchange with water. Such a high degree of flexibility of the inter-domain linker might be required for IF3 domains to interact with distant regions of the ribosome.

Bacterial Proteins↗
PubMed1997

Comparison of aceclofenac with piroxicam in the treatment of osteoarthritis.

A multicentre, double-blind, randomised, parallel group study was undertaken to investigate the efficacy and safety of aceclofenac (123 patients, 100 mg twice daily) in comparison to piroxicam (117 patients, 20 mg once daily and placebo once daily) in patients with osteoarthritis of the knee. The treatment period of two months was preceded by a washout period of one week duration. On completion of the study, patients in both aceclofenac and piroxicam-treated groups exhibited significant improvement in pain intensity and functional capacity of the affected knee, as represented by the Osteoarthritis Severity Index (OSI) (p < 0.0001 and p < 0.001 respectively). This was further substantiated following the patient's assessment of pain intensity using the Visual Analogue Scale (VAS), in which significant improvements were demonstrated at all time points for each treatment group (p < 0.001). Although both treatment groups showed a significant improvement in all investigator's clinical assessments (functional exploration of the knee, knee flexion and extension (EXT)), there were no significant differences between the groups. There was, however, a more rapid improvement in knee flexion in the aceclofenac group after 15 days of treatment. Both aceclofenac and piroxicam were well tolerated by patients, the most commonly reported adverse events being gastrointestinal, although their incidence was low. Only 24 patients on aceclofenac, as opposed to 33 on piroxicam complained of dyspepsia, epigastralgia and pyrosis. While 7 patients in each group were withdrawn because of adverse events, only one patient with piroxicam was withdrawn because of severe upper gastrointestinal bleeding. Twice as many reports of fecal blood loss were made in the piroxicam group in comparison to the aceclofenac group. In summary, this study confirms the therapeutic efficacy of aceclofenac and suggests that it is a well-tolerated alternative NSAID to piroxicam in the treatment of osteoarthritis.

Adult↗
PubMed1997

Magnetic stimulation in Alzheimer's disease.

Alzheimer's disease (AD) is a common cause of dementia in which some clinical motor abnormalities have been described. We used transcranial magnetic stimulation in order to test the hypothesis that the change in the motor cortex might cause modifications in motor excitability. Fourteen mildly to moderately affected AD patients were compared with 11 controls matched for age, height and sex. The motor evoked potential threshold value for the relaxed abductor digiti minimi was lower in the AD patients than in the control group for both left and right hemispheres (P < 0.05). No statistically significant difference was found comparing the left and the right hemispheres thresholds in each population. The mean interside threshold differences were small and not significantly different between patients and controls. The spinal motor neuron excitability, as evaluated by F/M and H/M waves amplitude ratios, showed no difference between the groups, reinforcing the motor cortex increased excitability hypothesis to explain this difference. Degeneration of inhibitory gabaergic terminals might be the basis for the increased cortical excitability in the motor cortex of the Alzheimer patients; postsynaptic changes in the GABAA receptors might also affect inhibitory gabaergic transmission. The increased excitability found by transcranial magnetic stimulation in the motor cortex is important for understanding the emergence of seizures and myoclonus in this disease.

Aged↗