Biomedical subjects

P Ribeiro

Publications and source records attributed to P Ribeiro.

At least 19 recordsLinked to original sources

PubMed2005

Effects of caffeine on the electrophysiological, cognitive and motor responses of the central nervous system.

Caffeine is the most consumed psychoactive substance in the world. The effects of caffeine have been studied using cognitive and motor measures, quantitative electroencephalography (qEEG) and event-related potentials. However, these methods are not usually employed in combination, a fact that impairs the interpretation of the results. The objective of the present study was to analyze changes in electrophysiological, cognitive and motor variables with the ingestion of caffeine, and to relate central to peripheral responses. For this purpose we recorded event-related potentials and eyes-closed, resting EEG, applied the Stroop test, and measured reaction time. Fifteen volunteers took caffeine (400 mg) or placebo in a randomized, crossover, double-blind design. A significant reduction of alpha absolute power over the entire scalp and of P300 latency at the Fz electrode were observed after caffeine ingestion. These results are consistent with a stimulatory effect of caffeine, although there was no change in the attention (Stroop) test or in reaction time. The qEEG seems to be the most sensitive index of the changes produced by caffeine in the central nervous system since it proved to be capable of detecting changes that were not evident in the tests of cognitive or motor performance.

Adult↗

PubMed2004

Aperiodic quantum random walks.

We generalize the quantum random walk protocol for a particle in a one-dimensional chain, by using several types of biased quantum coins, arranged in aperiodic sequences, in a manner that leads to a rich variety of possible wave-function evolutions. Quasiperiodic sequences, following the Fibonacci prescription, are of particular interest, leading to a sub-ballistic wave-function spreading. In contrast, random sequences lead to diffusive spreading, similar to the classical random walk behavior. We also describe how to experimentally implement these aperiodic sequences.

Journal Article↗

PubMed2003

Clinical performance of non-contact tonometry by Reichert AT550 in glaucomatous patients.

Measuring intraocular pressure (IOP) by non-contact tonometry (NCT) has been demonstrated to be a valid and reliable technique to be used in primary eye care; it is easier to use, it does not transmit infectious diseases, and it is not necessary to use anaesthetic or staining eye drops. Recently, a new NCT device has showed an excellent level of agreement with Goldmann tonometry, but there are no records of its performance in glaucomatous eyes. To rectify this, IOP was measured in twenty-two patients (44 eyes) receiving medical treatment to control elevated IOP, with AT550 and Goldmann tonometry. Mean values of IOP were 18.98 +/- 2.77 and 19.08 +/- 3.02 mmHg using Goldmann and AT550, respectively. Plots of differences against means displayed good agreement (mean difference +/- limits of agreement, -0.09 +/- 3.30); this value was not significantly different from zero (t-test for dependent samples, p = 0.709). In conclusion, IOP values as measured with the AT550 NCT are clinically comparable with those obtained with Goldmann tonometry in glaucomatous patients. This validates this NCT not only for screening of IOP but to follow-up glaucomatous patients with a rapid, non-invasive method.

Exfoliation Syndrome↗

PubMed2001

A Schistosoma mansoni Pad1 homologue stabilizes c-Jun.

We report the cloning and functional analysis of a Pad1 homologue (SmPOH) from Schistosoma mansoni. SmPOH encodes a protein of approximately 35 kDa with high amino acid identities to yeast Pad1 (65%) and its human homologue, POH1 (78%). Members of the Pad1 family are subunits of the 26S proteasome and have been implicated as positive modulators of transcription in yeast. Recombinant SmPOH expressed in COS7 cells exhibited a punctate pattern of distribution throughout the cytoplasm and nucleus, predominantly in the nuclear periphery, a distribution consistent with that of the cellular proteasome. Transient overexpression of SmPOH in COS7 cells caused a dose-dependent stimulation in AP-1 transcriptional activity, as determined by a reporter gene assay. This effect was associated with a pronounced increase in the levels of cellular c-Jun. In vitro degradation assays further demonstrated that SmPOH specifically decreased the rate of c-Jun degradation in a dose dependent manner. Taken together, these results suggest that SmPOH, and possibly other related Pad1 proteins, function as positive modulators of transcription by increasing the stability of cellular c-Jun, making elevated amounts of this protein available for transactivation of AP-1-responsive genes.

Amino Acid Sequence↗

PubMed2000

Immunophenotypic aberrations, DNA content, and cell cycle analysis of plasma cells in patients with myeloma and monoclonal gammopathies.

We describe the immunophenotypic and gross DNA defects in 55 patients with myeloma and 50 patients with monoclonal gammopathy and review the literature on this subject (MedLine, 1994-2000). Our data confirmed previous reports indicating that in myeloma nearly all marrow plasma cells are abnormal (98.7 +/- 8.1%). In monoclonal gammopathy the fraction of abnormal plasma cells was 35.0 +/- 32.8%. In both myeloma and monoclonal gammopathy, the most frequent aberrant phenotypic features consisted of absence of expression of CD19, strong expression of CD56, and decreased intensity of expression of CD38; aberrant expression of CD10, CD20, CD22, or CD28 was observed in less than one-third of myeloma cases. The vast majority of cases had two or more phenotypic aberrations. In the DNA studies, 7% of myeloma cases were biclonal and 93% of cases were monoclonal. In those studies with only one plasma cell mitotic cycle, 37% had normal DNA content and 63% were aneuploid (hyperploid, 61%; hypoploid, 2%). The mean percentages of plasma cells in S- and G2M phases were 4.9 +/- 8.5 and 4.4 +/- 6.9%, respectively. Thirty-eight percent of cases had more than 3% of plasma cells in S phase. In monoclonal gammopathy, the DNA index of abnormal plasma cells ranged from 0.89 to 1.30 and the percentage of diploid (31%) and aneuploid (69%) cases was not different from the results found in myeloma. The differences in percentage of abnormal plasma cells in S- (7.4 +/- 8.6%) and G2M-phases (2.4 +/- 1.7%) in patients with monoclonal gammopathy were not statistically significant.

Adult↗

PubMed2000

Expression of genes coding for the tumor necrosis factor and lymphotoxin ligand-receptor system in non-Hodgkin's lymphomas.

Excessive production of the tumor necrosis factor (TNF) ligand-receptor system has been found to contribute to the severity of non-Hodgkin's lymphoma (NHL). We therefore investigated the expression of TNF, lymphotoxin alpha (LTalpha), lymphotoxin beta (LTbeta), and their receptor (p55, p75, LTbeta-R) transcripts within the tumor tissue in different NHL histological subtypes. The constitutive expression of genes coding for TNF-related ligands and receptors was found in almost all 31 NHL samples studied. Semi-quantitative reverse transcription/polymerase chain reaction and computed densitometry assays revealed that the amounts of TNF, LTalpha, p55, and LTbeta-R mRNA were higher in follicular NHL than in other histological entities. Therefore tumor cell immunopurification was performed in representative follicular NHL samples and consistent results were obtained. The pattern of LTbeta gene expression was different from that of the other molecules, indicating the existence of distinct mechanisms of gene regulation. These results indicate that the transcription of genes coding for the TNF ligand-receptor system in NHL tumor tissue is more widespread than originally thought and that the heterogeneity of their expressions might be related to histological features. The expression of TNF-related ligands and receptors in tumor tissues is likely to contribute to the clinicopathological features of lymphoid-derived malignancies.

Adult↗

PubMed1999

Characterization of a stable form of tryptophan hydroxylase from the human parasite Schistosoma mansoni.

A cDNA (Schistosoma mansoni tryptophan hydroxylase; SmTPH) encoding a protein homologous to tryptophan hydroxylase, the enzyme that catalyzes the rate-limiting step in the biosynthesis of serotonin, was cloned from the human parasite Schistosoma mansoni. Bacterial expression of SmTPH as a histidine fusion protein produced soluble active enzyme, which was purified to apparent homogeneity and a final specific activity of 0.17 micromol/min/mg of protein. The purified enzyme was found to be a tetramer of approximately 240 kDa with a subunit size of 58 kDa. Several of the biochemical and kinetic properties of SmTPH were similar to those of mammalian tryptophan hydroxylase. Unlike the mammalian enzyme, however, SmTPH was found to be stable at 37 degrees C, its t((1)/(2)) being nearly 23 times higher than that of a similarly expressed rabbit tryptophan hydroxylase. A semiquantitative reverse transcription polymerase chain reaction showed that the level of SmTPH mRNA in a larval stage of the parasite (cercaria) is 2.5 times higher than in adult S. mansoni, suggesting possible differences in the level of enzyme expression between the two developmental stages. This study demonstrates for the first time the presence of a functional tryptophan hydroxylase in a parasitic helminth and further suggests that the parasites are capable of synthesizing serotonin endogenously.

Amino Acid Sequence↗

PubMed1999

Long term outcome of patients with hairy cell leukemia treated with pentostatin.

BACKGROUND: With the introduction of new drugs such as interferon-alpha (IFN) and purine analogs, the management of hairy cell leukemia (HCL) patients has changed. However, pentostatin has been found to produce higher complete remission rates than IFN. The current study was undertaken to investigate response and long term follow-up in HCL patients treated with pentostatin. METHODS: Between March 1989 and October 1996, 49 patients with HCL and 1 patient with a HCL variant were treated with pentostatin. Eighteen patients had received no prior therapy, 31 patients had received prior treatment with IFN, and 1 patient had received prior treatment with 2'-chlorodeoxyadenosine (2'CdA) and IFN. All patients except 1 were treated with a dose of 4 mg/m2 every 2 weeks. The median number of cycles was 12. RESULTS: The overall response rate was 96% (48 of 50 patients); 22 patients (44%) achieved a complete response, 18 patients (36%) achieved a good partial response (defined as residual bone marrow infiltration < 5%), 8 patients (16%) achieved a partial response, and 2 patients died. For a median follow-up of 33 months off therapy, there were 5 recurrences between 12-66 months; 3 of these patients were treated further with and responded to 2'CdA and 2 died of disease progression at 12 and 40 months, respectively. In addition, 3 patients died of unrelated causes (1 of very early infection, 1 of toxic death and another of cardiac arrest) comprising an overall death rate of 14% (7 of 50 patients). The overall survival rate was 86% for a median follow-up of 38 months (range, 8-105 months). Major side effects were febrile episodes, herpes zoster, nausea/emesis, and pancytopenia. CONCLUSIONS: This analysis confirms both the high remission rate and durable responses that may be achieved with pentostatin treatment in HCL patients. Although pentostatin is active, the risk of cytopenia and immunosuppression must be evaluated carefully.

Adult↗

PubMed1999

Clinical heterogeneity of autosomal recessive spastic paraplegias: analysis of 106 patients in 46 families.

BACKGROUND: Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders characterized by progressive and predominant spasticity of the lower limbs, in which dominant, recessive, and X-linked forms have been described. While autosomal dominant HSP has been extensively studied, autosomal recessive HSP is less well known and is considered a rare condition. OBJECTIVE: To analyze the clinical presentation in a large group of patients with autosomal recessive HSP from Portugal and Algeria to define homogeneous groups that could serve as a guide for future molecular studies. RESULTS: Clinical features in 106 patients belonging to 46 Portuguese and Algerian families with autosomal recessive HSP are presented, as well as the results of molecular studies in 23 of these families. Five phenotypes are defined: (1) pure early-onset families, (2) pure lateonset families, (3) complex families with mental retardation, (4) complex families with mental retardation and peripheral neuropathy, and (5) complex families with cerebellar ataxia. Six additional families have specific complex presentations, each of which is unique in the present series. Pyramidal signs in the upper limbs and pes cavus are frequent findings, while pseudobulbar signs, including dysarthria, dysphagia, and brisk jaw jerks, are more frequent in the complex forms. The complex forms have a poorer prognosis, while pure forms, particularly those with early onset, are more benign. One Algerian pure early-onset kindred was linked to the locus on chromosome 8, previously reported in 4 Tunisian families. Two of the Portuguese kindreds with complex forms (one with mental retardation and the other associated with hypoplasia of the corpus callosum) showed linkage to the locus recently identified on chromosome 16. CONCLUSIONS: Although autosomal recessive HSP represents a heterogeneous group of diseases, some phenotypes can be defined by analyzing a large group of patients. The fact that only one Algerian family was linked to chromosome 8 suggests that this is a rare localization even in kindreds with the same ethnic background. Linkage to chromosome 16 was found in 2 clinically diverse Portuguese kindreds, illustrating that this locus is also rare and may correspond to different phenotypes.

Adolescent↗

PubMed1999

Haemonchus contortus: characterization of a glutamate binding site in unselected and ivermectin-selected larvae and adults.

A specific ivermectin-sensitive, glutamate binding site has been identified in the parasitic nematode Haemonchus contortus. Glutamate binding in H. contortus was saturable and occurred in a single class of high-affinity binding sites which appeared to have pharmacological properties different from those of mammalian glutamate receptors. Adult and larval forms of H. contortus had dramatically different glutamate binding kinetics, the larvae showing nearly up to 200-fold higher Bmax values and up to 9-fold increases in Kd values compared to adults. Treatment of adult H. contortus with the anthelmintic, ivermectin, decreased the Bmax value for glutamate binding in the susceptible strain but not in the resistant parasites. Furthermore, selection for ivermectin resistance was associated with a significant increase in Bmax for glutamate binding in adults and a similarly significant increase in glutamate binding affinity in larvae. These results suggest that the H. contortus glutamate binding site identified in this study may be involved in the phenomenon of ivermectin resistance.

Animals↗

PubMed1999

Haemonchus contortus: effects of glutamate, ivermectin, and moxidectin on inulin uptake activity in unselected and ivermectin-selected adults.

Using [(3)H]inulin uptake as a measure of pharyngeal pumping activity, we have investigated and compared the effects of glutamate, ivermectin, and moxidectin on inulin uptake in susceptible and ivermectin-selected Haemonchus contortus. Inulin uptake is inhibited by glutamate, ivermectin, and moxidectin, at biologically relevant concentrations. Glutamate influences the responses to both ivermectin and moxidectin, suggesting that these three substances share a common mechanism of action. The effects of ivermectin on inulin uptake, but not moxidectin, are significantly altered as a result of selection with ivermectin. These results suggest that ivermectin and moxidectin may differ, to some extent, in their mode of action responses or mechanisms of resistance.

Animals↗

PubMed1999

Characterization of germinal center dendritic cells in follicular lymphoma.

A subset of dendritic cells called germinal center dendritic cells (GCDC) has recently been described inside germinal center from reactive lymphoid organs. We investigated this newly recognized population in follicular lymphoma (FL), which is considered to be the pathologic counterpart of germinal center B cells. Immunohistochemistry analysis with a panel of antibodies demonstrated the presence of a cell population with the peculiar GCDC phenotype in FL biopsies and a similar localization of these cells inside tumoral and reactive follicles. Therefore, we analyzed the relationships between GCDC and the other cell subsets of the tumor follicles. Some of CD4+ and CD8+ T lymphocytes present inside the follicle were found to be in close association with GCDC, suggesting a potential implication of GCDC in their activation. In addition, the distribution of GCDC inside FL and reactive follicles did not appear disrupted, in contrast to follicular dendritic cells, the other follicle dendritic cell type. Finally, we demonstrated that GCDC could be detected from FL lymph node cell suspension by flow cytometry. Taken together, these results indicate that FL development is not associated with a disappearance of GCDC or with a lack of physical interactions between GCDC and T cells inside the follicles. In addition, the fact that GCDC can be observed in FL samples by flow cytometry should allow their purification to further study their putative role in FL development and maintenance.

Adult↗

PubMed1999

Characterization of a novel serotonin receptor from Caenorhabditis elegans: cloning and expression of two splice variants.

Serotonin [5-hydroxytryptamine (5-HT)] modulates feeding activity, egg-laying, and mating behavior in the free-living nematode, Caenorhabditis elegans. We have cloned a novel receptor cDNA from C. elegans (5-HT2Ce) that has high sequence homology with 5-HT2 receptors from other species. When transiently expressed in COS-7 cells, 5-HT2Ce exhibited 5-HT binding activity and activated Ca2+-mediated signaling in a manner analogous to other 5-HT2 receptors. However, 5-HT2Ce displayed unusual pharmacological properties, which resembled both 5-HT2 and 5-HT1-like receptors but did not correlate well with any of the known 5-HT2 subtypes. Two splice variants of 5-HT2Ce that differ by 48 N-terminal amino acids were identified. The two isoforms were found to have virtually identical binding and signaling properties but differed in their levels of mRNA expression, with the longer variant being four times more abundant than the shorter species in all developmental stages tested. Taken together, the results describe two variants of a novel C. elegans 5-HT receptor, which has some of the properties of the 5-HT2 family but whose pharmacological profile does not conform to any known class of receptor.

Aequorin↗

PubMed1999

Short-term intensive consolidation therapy after all-trans retinoic acid in acute promyelocytic leukemia.

Complete remission induced by all-trans retinoic acid (ATRA) in acute promyelocytic leukemia is short lived, and several consolidation chemotherapy courses usually are given to reduce the relapse rate. To assess the value of short-term intensive consolidation, 38 patients with newly diagnosed acute promyelocytic leukemia entered a prospective study in which induction therapy with ATRA immediately was followed by a single course of mitoxantrone plus high-dose cytarabine (3 g/m2 every 12 hours, days 1-4), with no further treatment. Complete remission was achieved in 31 patients (81.6%) after a median time of 49 days of ATRA (to which chemotherapy was added at entry in 10 patients with leukocytosis). Thirty patients received the planned consolidation course. After a median follow-up of 36 months, four of these patients have relapsed and 24 are still in first complete remission, for an estimated disease-free survival of 75% at 60 months. The authors conclude that this single course consolidation of ATRA-induced remission provides excellent long-term control of acute promyelocytic leukemia.

Adult↗

PubMed1999

Modulation of costimulatory molecules on follicular lymphoma cells by TNF and CD40.

TNF has recently been implicated in the formation of germinal center cells in lymphoid organs. Follicular lymphoma (FL) is thought to represent the pathological counterpart of germinal center B-cell. High levels of TNF and its soluble receptors were found in the plasma of FL patients whereas the transcripts of these molecules were previously found to be present in FL patients lymph nodes. We therefore studied here the effects of TNF on the expression of costimulatory molecules implicated in the cytotoxic T cell response on purified FL cells. In contrast to results described with B-type chronic lymphocytic leukemia, also characterized by high levels of circulating TNF, none of the tested samples showed a regulation of CD80, CD86, CD27 and CD70 in response to TNF. To confirm that the lack of regulation of these molecules was not due to the FL cells inability to modulate their expression, we therefore analyzed costimulatory molecules expression after CD40 pathway stimulation. After culture with human CD40L-transfected L-cells, an up-regulation of CD80, CD86 and CD70 expression was observed, while TNF addition in this model did not influence these changes. In this context, the CD27 molecule was down-regulated except in a single case, where its expression was increased. Taken together, this data demonstrates that in vitro expression of costimulatory molecules such as CD80, CD86, CD27 and CD70, which are implicated in the anti-tumoral response, can be regulated by CD40 ligand but not by TNF.

Aged↗

PubMed1998

Genetic polymorphisms in the tumor necrosis factor locus influence non-Hodgkin's lymphoma outcome.

Systemic release of tumor necrosis factor (TNF) and lymphotoxin-alpha (LTalpha) has been found to contribute to the severity of non-Hodgkin's lymphoma (NHL). We investigated whether genetic polymorphisms in the TNF locus, previously shown to influence TNF and LTalpha genes expression, might contribute to these cytokines production and to the clinical course of NHL. Genomic DNA from 273 lymphoma patients was typed for TNF (-308) polymorphism using an allele-specific polymerase chain reaction (PCR) and for LTalpha (+252) polymorphism with a PCR-based restriction fragment length polymorphism. The presence of the TNF allele involved in increased TNF gene transcription was associated with higher plasma levels of this cytokine at the time of lymphoma diagnosis (chi2 test, P = .013). An extended haplotype analysis showed that the presence of at least two TNF or LTalpha high-producer alleles constituted a risk factor for first-line treatment failure (chi2 test, P = .021), shorter progression-free survival (log-rank test, P = .0007), and overall survival (log-rank test, P = .012). In the subgroup of 126 patients with diffuse large-cell lymphoma, the presence of two or more TNF/LTalpha high producing alleles contributed significantly to a higher rate of relapse and progression (log-rank test, P = .045 and P = .027). In multivariate Cox regression models including the variables of the International Prognostic Index, the TNF/LTalpha haplotype status was found to be an independent risk factor for progression-free survival (relative risk 2.33, 95% confidence interval [1.17 to 4.64], P = . 0053) and overall survival (relative risk 1.92, 95% confidence interval [0.63 to 5.80], P = .081) of large-cell lymphoma patients. These results indicate that genetic polymorphism leading to increased TNF production influences the outcome of NHL and suggest a pathophysiological role for the genetic control of the immune response in lymphoid malignancies.

Adult↗

PubMed1998

Ivermectin resistance in nematodes may be caused by alteration of P-glycoprotein homolog.

Resistance to ivermectin and related drugs is an increasing problem for parasite control. The mechanism of ivermectin resistance in nematode parasites is currently unknown. Some P-glycoproteins and multidrug resistance proteins have been found to act as membrane transporters which pump drugs from the cell. A disruption of the mdrla gene, which encodes a P-glycoprotein in mice, results in hypersensitivity to ivermectin. Genes encoding members of the P-glycoprotein family are known to exist in nematodes but the involvement of P-glycoprotein in nematode ivermectin-resistance has not been described. Our data suggest that a P-glycoprotein may play a role in ivermectin resistance in the sheep nematode parasite Haemonchus contortus. A full length P-glycoprotein cDNA from H. contortus has been cloned and sequenced. Analysis of the sequence showed 61-65% homology to other P-glycoprotein/multidrug resistant protein sequences, such as mice, human and Caenorhabditis elegans. Expression of P-glycoprotein mRNA was higher in ivermectin-selected than unselected strains of H. contortus. An alteration in the restriction pattern was also found for the genomic locus of P-glycoprotein derived from ivermectin-selected strains of H. contortus compared with unselected strains. P-glycoprotein gene structure and/or its transcription are altered in ivermectin-selected H. contortus. The multidrug resistance reversing agent, verapamil, increased the efficacy of ivermectin and moxidectin against a moxidectin-selected strain of this nematode in jirds (Meriones unguiculatus). These data indicate that a P-glycoprotein may be involved in resistance to ivermectin and other macrocyclic lactones in H. contortus.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1998

A new death receptor 3 isoform: expression in human lymphoid cell lines and non-Hodgkin's lymphomas.

Two isoforms encoding the full-length transmembrane death receptor 3 (DR3) were isolated from mRNAs of a panel of human cell lines and tumor tissues obtained from patients with follicular non-Hodgkin's lymphoma. A new DR3 variant (DR3 beta) was characterized by 2 insertions of respectively 20- and 7-base pairs (bp) which result in a predictive translated polypeptide differing from the described DR3 molecule by a 28 amino-acid stretch in the extracellular domain. DR3 was shown to be expressed in all cell lines and lymphoma samples tested, whereas DR3 beta expression was restricted to lymphoid T-cell and immature B-cell lines and to selected cases with follicular lymphoma. These data provide new insight into the molecular heterogeneity of DR3, suggesting the presence of several receptor isoforms that can participate in lymphoid cell homeostasis.

Base Sequence↗