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Biomedical subjects

A Martinez

Publications and source records attributed to A Martinez.

At least 37 records · Page 2Linked to original sources

Chvostek's sign and hypocalcaemia in children with seizures.

Chvostek's sign (CS) was investigated in 154 patients with seizures (epilepsy, n = 91; non-epileptic event, n = 41; febrile convulsion, n = 19; hypocalcaemic seizure, n = 3). Patients with febrile convulsions or non-epileptic seizures had either negative or mild CS. Marked CS was only found among those with the diagnosis of epilepsy or hypocalcaemia. Normocalcaemic patients had no other signs of neuromuscular hyperexcitability (NMH) while those with hypocalcaemia manifested positive Trousseau's sign (TS) and other signs of NMH. There was no significant correlation between CS and seizure control, epilepsy classification and EEG findings.

Adolescent↗

Analysis of factors affecting PBPC collection in low-weight children with malignant disorders.

BACKGROUND: PBPC collection in children weighing </=25 kg is hampered by technical and clinical problems related to vascular access, low total blood volume, anticoagulation, side effects, and psychological impact. The aim of this study was to analyze several clinical and technical factors, other than pre-apheresis CD34(+) count, that may affect PBPC collection in these low-weight children. METHODS: Data from 88 leukaphereses performed in 45 children were analyzed, including pre-apheresis CD34(+) cell count, COBE Spectra software (version 4.7 versus 6.0), apheresis volume [standard versus large-volume leukapheresis (LVL)] and patient's diagnosis, age, weight and sex. RESULTS: The median number of PBPC collected was 6.68 mononuclear cells (MNC)x10(8)/kg (range 2.36-19.05) and 1.69 CD34(+) cellsx10(6)/kg (range 0.08-13.79). Multivariate analysis showed that factors independently associated with the CD34(+) cell yield per apheresis were pre-apheresis CD34(+) cell count (P<0.001), diagnosis (P=0.008) and apheresis volume (P=0.009). Recruitment of CD34(+) cells was also independently affected by the apheresis volume, being higher in the LVL group (P=0.008). DISCUSSION: We have demonstrated that, apart from the well-known influence of the pre-apheresis CD34(+) cell count, two other factors have a major impact on the CD34(+) cell yield: patient's diagnosis and apheresis volume. In addition, taking into account that side effects were mild and tolerable, we have confirmed that LVL is a safe and effective procedure in children </=25 kg, and that AutoPBSC software could be reliably used in these patients, provided that an experienced team performs the procedure.

Antigens, CD34↗

ACTH and PRL sensitivity of highly differentiated cell lines obtained by adrenocortical targeted oncogenesis.

We established cell lines from adrenal tumors of transgenic mice harboring the large T-antigen of simian virus 40 under the control of the adrenocortical specific promoter of the scavenger aldose reductase-like akr1b7 gene. Mass spectrometry analyses of serum-supplemented or serum-free culture media showed that ATC1 line secreted only corticosterone. These cells, propagated over 25 passages, were characterized with regard to ACTH and PRL responsiveness, as measured by increased corticosterone production, induction of genes involved in the different steps of steroidogenesis (cholesterol delivery, steroid biosynthesis and detoxification of by-products) and expression of transcriptional regulators (SF-1 and DAX1). Corticosterone secretion (RIA) in serum-free medium was stimulated over 12-fold after 6 h treatment with either 10(-9)M ACTH or PRL and both hormones seemed equivalent in promoting this secretion (149 +/- 14 ng and 145 +/- 18 ng/10(6) cells/6 h, respectively). As expected, Northern blots indicate that ATC1 cells expressed mRNAs for the enzymes of corticosterone metabolism CYP11B1 and CYP21A, as well as those for the proteins SIK, SRB1, StAR, CYP11A1, and AKR1B7. Interestingly, these cells have maintained not only the expression of SF-1 but also that of DAX1. No expression of the zona glomeruloza-specific cyp11b2 gene was detected. With the exception of cyp21a and mc2r genes which were constitutively expressed, most of the genes above mentioned were induced in a time- and dose-dependent fashion in response to ACTH or PRL while DAX1 was repressed. Importantly, hormone-mediated repression of DAX1 gene expression was also observed in vivo in mice adrenals. Altogether these data demonstrate that ATC1 line provided an unique model of well differentiated zona fasciculata immortalized cells suitable for the dissection of molecular events leading to ACTH and PRL regulation of adrenal functions.

Adrenal Cortex Neoplasms↗

Glucocorticoid-inducible gene expression vectors for use in Drosophila melanogaster Schneider 2 cells.

Inducible, vector-based, expression systems that allow fine control of transgene expression are gaining more and more use in fundamental research as well as in therapeutic applications. In an effort to develop a tightly regulated heterologous expression system for Drosophila Schneider 2 cells, three different inducible reporter constructs were compared. These comprised six copies of the glucocorticoid response element fused to one of three distinct types of Drosophila gene promoters: (1) a TATA-box containing, (2) a TATA-less and (3) a bidirectional core sequence. These were fused to a luciferase reporter gene. The promoter constructs displayed different basal as well as agonist-induced activities. The implications of the observations made are discussed in the context of promoter properties and of induction of genes that may be studied in Drosophila.

Animals↗

Vascular anomalies in Proteus syndrome.

Proteus syndrome (PS) is a complex hamartomatous disorder defined by local overgrowth (macrodactyly or hemihypertrophy), subcutaneous tumours and various bone, cutaneous and/or vascular anomalies (VA). VA are manifold in PS, but their prevalence is unknown so far. In order to further characterize PS, we studied the prevalence of VA in 22 PS patients presenting to our outpatient clinic and reviewed 100 PS patients previously reported between 1983 and 2001. The diagnosis of vascular abnormalities was made on clinical grounds and supported with imaging studies and/or histology in 12 and seven patients out of 22, respectively. Thirty-five VA were identified in 22/22 (100%) of our patients, and more than one type of VA were present in 10 of them. Vascular tumours, portwine stains (PWS), and venous anomalies (varicosities, prominent veins) were equally common. A total of 118 VA were previously reported in 70/100 (70%) PS patients; vascular hamartomas were more prevalent (56/118 = 47.5%), whilst PWS (21.2%) and venous anomalies (22.9%) were slightly less common than in our series, but there is the possibility of under-reporting. Unlike Klippel-Trenaunay syndrome, where VA are mostly confined to the hypertrophic limb, major arteriovenous anomalies are rare, and - similar to the other hamartomas and naevi observed in PS (pigmentary naevi, epidermal naevi, subcutaneous tumours, exostoses) - VA appear to be distributed at random sites on the body. We conclude that VA are among the most common findings in PS. Their varying type and distribution lend further support to the concept of somatic mosaicism.

Abnormalities, Multiple↗

GSK-3 inhibitors: discoveries and developments.

Glycogen synthase kinase 3 (GSK-3) in the 21(st) century emerged as one of the most attractive therapeutic target for the development of selective inhibitors as new promising drugs for unmet pathologies including Alzheimer's disease, stroke, bipolar disorders, chronic inflammatory processes, cancer and diabetes type II. The full potential of GSK-3 inhibitors is just starting to be realized but the number of candidates in development provided by both academic centres and pharmaceutical companies have increased exponentially in the last two years. This review discloses recent discoveries and developments on peptides and small molecules targeting GSK-3. Focusing attention on this exciting target could thus reap considerable clinical and economic rewards.

Animals↗

Analysis of adiabatic coupling between photonic crystal single-line-defect and coupled-resonator optical waveguides.

A detailed analysis of adiabatic coupling between conventional photonic crystal single-line-defect and coupled-resonator optical waveguides is reported. Adiabatic coupling by progressive variation of the radii of the spacing defects between cavities is investigated. Flat transmission spectra with coupling efficiencies greater than 90% are achieved in a broad frequency range with short coupling lengths. Moreover, we find that flat transmission at low frequencies requires longer coupling lengths partly because the requirements imposed for adiabatic transmission in photonic crystals are violated.

Journal Article↗

Dynamics of feature binding during object-selective attention.

Objects in the environment may be attended selectively and perceived as unified ensembles of their constituent features. To investigate the timing and cortical localization of feature-integration mechanisms in object-based attention, recordings of event-related potentials and magnetic fields were combined with functional MRI while subjects attended to one of two superimposed transparent surfaces formed by arrays of dots moving in opposite directions. A spatiotemporal analysis revealed evidence for a rapid increase in neural activity localized to a color-selective region of the fusiform gyrus when the surface moving in the attended direction displayed an irrelevant color feature. These data provide support for the "integrated-competition" model of object-selective attention and point to a dynamic neural substrate for the rapid binding process that links relevant and irrelevant features to form a unified perceptual object.

Adult↗

Response to different environmental stress conditions of industrial and laboratory Saccharomyces cerevisiae strains.

Two sets of Saccharomyces cerevisiae strains were compared for their physiological responses to different stress conditions. One group is composed of three strains adapted to controlled laboratory conditions (CEN.PK, LR88 and RS58), whereas the other consisted of five industrial strains (IND1101, SuperStart, LO24, LO41 and Azteca). Most industrial strains showed higher tolerance to heat shock and to an oxidative environment than laboratory strains. Excluding CEN.PK, a similar behavior was observed regarding ethanol production in high sugar concentrations (180 g/l glucose). Addition of acetate (10 g/l) or furfural (2 g/l), in concentrations similar to those found in sugar cane bagasse hydrolysates, decreased cell mass formation and growth rate in almost all strains. CEN.PK and SuperStart showed the highest sensitivity when grown in furfural-containing medium. Acetic acid treatment severely affected cell mass formation and reduced growth rate in all strains; CEN.PK and LO24 were the most resistant. The specific ethanol production rate was not affected by furfural addition. However, specific ethanol production rates decreased in response to acetic acid in four industrial strains, and increased in all laboratory strains and in LO24. No significant correlation was found between the stress tolerance of the strains tested and the transcript accumulation of genes selected by their involvement in the response to each of the stressful environments applied.

Acetic Acid↗

Relationships between individual sensitivity to CS- and cocaine-induced reinstatement in the rat.

RATIONALE: Maintaining abstinence is highly challenging for cocaine ex-users. Exposure to drug conditioned stimuli (CS) and to low doses of cocaine can provoke craving in humans and reinstate self-administration (SA) behavior in animal models. Whether drug- and CS-induced reinstatement depend on the same biological substrates remains controversial. OBJECTIVES: We investigated the relationships between cocaine- and CS-induced SA reinstatement within the same individuals as a function of the duration of the withdrawal period after cessation of extended cocaine SA. METHODS: Sprague-Dawley rats were trained for cocaine intravenous SA (0.8 mg/kg per infusion) during 74 sessions (2 h daily exposure to cocaine) and submitted to withdrawal. Five and 30 days after the end of SA, cocaine- and CS-induced reinstatement were tested. RESULTS: Both after a short and a long withdrawal, CS- and cocaine-induced reinstatement were not related. Furthermore, cocaine-induced reinstatement measured after a short and a long withdrawal was positively related while CS-induced reinstatement was not. The sensitivity of an individual to cocaine-induced reinstatement is not related to its sensitivity to CS-induced reinstatement. Furthermore, vulnerability to cocaine-induced reinstatement is determined quickly after SA cessation and is a long lasting state, whilst vulnerability to CS-induced reinstatement develops quickly or slowly depending on the individual. CONCLUSIONS: These results support the view that cocaine and CS induce reinstatement through different mechanisms. They imply that reinstatement in drug abuse is a heterogeneous condition with some individuals being more sensitive to one factor than to the other. Research for effective anti-relapse therapies should take these elements into account.

Animals↗

Diffuse large B-cell lymphoma arising from donor lymphoid cells after renal and pancreatic transplantation.

A patient with both a renal and pancreatic transplantation developed a diffuse large B-cell lymphoma, Epstein-Barr virus-related, 14 months after the surgical procedure. Tumor was confined to the transplanted organs: head of the pancreas and hilar lymph node of the transplanted kidney. Chimerism analysis demonstrated the tumor origin from donor lymphoid cells. Immunosuppression was discontinued and chemotherapy with cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone (CHOP) was started. However, no response was observed after three courses of this regimen. Finally, a transplantectomy was carried out, followed by rituximab (anti-CD20 antibody), with the patient achieving a complete response (CR). Two years later the patient remains in CR.

Adult↗

Parametric manipulation of conflict and response competition using rapid mixed-trial event-related fMRI.

In the current study we examined the influence of preceding context on attentional conflict and response competition using a flanker paradigm. Nine healthy right-handed adults participated in a rapid mixed trial event-related functional magnetic resonance imaging (fMRI) study, in which increasing numbers of either compatible or incompatible trials preceded an incompatible trial. Behaviorally, reaction times on incompatible trials increased as a function of the number of preceding compatible trials. Several brain regions showed monotonic changes to the preceding context manipulation. The most common pattern was observed in anterior cingulate, dorsolateral prefrontal, and superior parietal regions. These areas showed an increase in activity for incompatible trials as the number of preceding compatible trials increased and a decrease in activity for incompatible trials as the number of preceding incompatible trials increased. Post hoc analysis showed that while the MR signal in the anterior cingulate and dorsolateral prefrontal regions peaked before the superior parietal region, the dorsolateral prefrontal MR signal peaked early and remained at this level. These findings are consistent with the conflict monitoring theory that postulates that the anterior cingulate cortex detects or monitors conflict, while PFC is involved in control adjustments that may then lead to modulation of superior parietal cortex in top-down biasing of attention.

Adult↗

Genetic polymorphisms in Spanish rheumatoid arthritis patients: an association and linkage study.

HLA polymorphism accounts only for approximately one-third of the genetic predisposition to rheumatoid arthritis (RA). To investigate the role of other loci in the susceptibility to RA, we have performed an analysis of several polymorphisms in genes of immune-related function: IL-10 -1082, -819, -592 promoter single nucleotide polymorphisms (SNPs), IL-10G and IL-10R microsatellites, IL-6 -622 promoter SNP, FcgammaRIIIA Val/Phe-158 polymorphism, IL-1 receptor antagonist VNTR, and the IKBL+738 T/C mutation. The analysis has been performed on a case-control study and also on RA trios. IL-10G12 was found to be associated with RA in the case-control study (18% in RA patients vs 9% in controls: P=0.001; pc<0.05). This allele was also more often transmitted than not transmitted (10 vs 5). No other allele in the present study is found to be associated to RA. Our data suggest that most of the loci studied play no major role in the susceptibility to RA, the IL-10 gene being the sole exception.

Arthritis, Rheumatoid↗

Reduced skin thickness: a new minor diagnostic criterion for the classical and hypermobility types of Ehlers-Danlos syndrome.

BACKGROUND: The diagnosis of Ehlers-Danlos syndrome (EDS) is mainly based on clinical criteria, although in some instances a sound molecular diagnosis is available. Clinical signs can be divided into two categories: one with high diagnostic specificity and the other with low specificity. Despite the fact that reduced skin thickness is one of the dermatological features in patients with EDS, this issue has not been analysed in greater detail. OBJECTIVES: To determine skin thickness in patients with the classical and the hypermobility types of EDS. METHODS: In 21 patients with classical type of EDS and in nine patients with hypermobility type of EDS, skin thickness was analysed at different body sites by cross-sectional b-mode scans obtained with a 20-MHz ultrasound system. RESULTS: We found a significant decrease in skin thickness in both types of EDS, which was highest at the chest and at the distal part of the lower leg. CONCLUSIONS: We propose that the reduced thickness of the dermis as determined by high-resolution 20-MHz ultrasound can be used as a new minor criterion in the diagnosis of the classical and the hypermobility types of EDS.

Ehlers-Danlos Syndrome↗

The effect of infusions of adrenaline, noradrenaline and dopamine on cerebral autoregulation under isoflurane anaesthesia in an ovine model.

The effects of infusions of adrenaline, noradrenaline and dopamine on cerebral autoregulation under steady-state isoflurane anaesthesia were compared with the awake state. Six studies each were conducted in two cohorts of adult ewes: awake sheep and those anaesthetized with 2% isoflurane anaesthesia. In random order, each animal received ramped infusions of adrenaline, noradrenaline (0-40 micrograms/min) and dopamine (0-40 micrograms/kg/min). Cerebral blood flow was measured continuously from changes in Doppler velocities in the sagittal sinus. Autoregulation was determined by linear regression analysis between cerebral blood flow and mean arterial pressure. Isoflurane did not significantly alter cerebral blood flow relative to pre-anaesthesia values (P > 0.05). All three catecholamines significantly and equivalently increased MAP from baseline in a dose dependent manner in both the awake and isoflurane cohorts. Although adrenaline significantly increased cerebral blood flow from baseline in the awake cohort (P < 0.01), none of the catecholamines significantly increased cerebral blood flow during isoflurane anaesthesia. No significant differences were demonstrated between the slopes and intercepts of regression lines for adrenaline, noradrenaline and dopamine within either cohort (ANCOVA). Inter-cohort comparisons between the two autoregulation curves demonstrated no significant difference between the slopes of the autoregulation curves for the awake (pooled slope = 0.39) and isoflurane cohorts (pooled slope = 0.28) (P > 0.05). Over a specific dose range, systemic hypertension induced by adrenaline, noradrenaline and dopamine did not significantly increase cerebral blood flow under 2% isoflurane anaesthesia. The concomitant administration of isoflurane and the catecholamines was not associated with altered autoregulatory function compared to the awake state.

Anesthesia, Inhalation↗

Primary follicular lymphoma arising in the ampulla of Vater.

Primary gastrointestinal lymphomas constitute more than one-third of all extranodal lymphomas, but among them follicular lymphomas (FL) are infrequent, accounting for only 1-4%. We report the case of a 55-year-old man diagnosed with a FL of the ampulla of Vater. He complained of dyspepsia. An upper gastroendoscopic study 1 year before showed a slight enlargement of the papilla with the biopsy initially interpreted as atypical follicular hyperplasia. The study performed because of persistence of the symptoms again showed an enlarged papilla, and the histological examination was diagnostic of FL (CD10+, bcl-2+). The full staging study did not show other FL involvement. The patient was treated with six courses of cyclophosphamide, hydroxydaunomycin, vincristine, and prednisone (CHOP), and the endoscopy as well as the biopsies revealed no abnormalities since the third course of chemotherapy. After 2 years of follow-up he remains asymptomatic and the gastroendoscopic study is normal.

Ampulla of Vater↗