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Biomedical subjects

P Ribeiro

Publications and source records attributed to P Ribeiro.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1998

Cloning and sequence analysis of a lysophospholipase homologue from Schistosoma mansoni.

A novel cDNA encoding a lysophospholipase (SmLPLH) homologue has been cloned from the human parasite, Schistosoma mansoni. The predicted primary structure of SmLPLH shares high sequence homology with mammalian lysophospholipases (62%) and also contains aconsensus signature peptide (GXSXG), which is present in all lipases. Two splice variants of SmLPLH that differ by 32 N-terminal amino acids were identified. The shorter truncated species carries a conserved S. mansoni spliced leader (SL) sequence at its 5' end and is believed to be formed by trans-splicing of the SL to an internal exon splice site. The functional significance of these two isoforms of SmLPLH is currently unknown.

Amino Acid Sequence↗
PubMed1998

Plasma levels of tumour necrosis factor and its soluble receptors correlate with clinical features and outcome of Hodgkin's disease patients.

A prospective study was performed to assess the use of plasma measurement of tumour necrosis factor (TNF), lymphotoxin alpha (LT alpha) and their soluble receptors (p55 and p75) for prognostic risk assignment in 61 patients with Hodgkin's disease. Plasma levels of TNF, p55 and p75, but not of LT alpha, were higher in Hodgkin's disease patients than in healthy controls. Plasma levels of TNF, p55 and p75 were associated with several prognostic factors for Hodgkin's disease, including those related to the host (age, performance status) and to the tumour (disease stage, extranodal site involvement, bulky tumour, serum levels of LDH and beta2-microglobulin, histology). Elevated plasma levels of TNF, p55 and p75 were also associated with several parameters reflecting an immune activation, including the presence of B symptoms, elevated serum levels of gammaglobulins, alkaline phosphatase and fibrinogen, as well as peripheral monocytosis, anaemia and low serum albumin levels. Finally, elevated TNF ligand receptor plasma markers were associated with a lower incidence of complete response to therapy and predicted shorter free-from-progression survival and overall survival of the patients. These results indicate that the plasma levels of TNF and its soluble receptors correlate with clinical features and outcome of patients with Hodgkin's disease.

Adolescent↗
PubMed1998

CD40 regulation of death domains containing receptors and their ligands on lymphoma B cells.

Within the tumour necrosis factor (TNF) family the induction of apoptosis is restricted to some ligand-receptors pairs, including TNF-TNF receptor type I (TNFRI/p55), FasL-Fas, TNF-related apoptosis-inducing ligand (TRAIL) and its death-receptors (DR)-4 and -5. The pair CD40L-CD40 belongs to the same family but rescues B cells from apoptosis. To investigate how these opposing actions are cross-linked, purified follicular lymphoma (FL) cells were activated upon a human CD40L-transfected murine fibroblastic layer, then RNA messengers for the above molecules were analysed using RT-PCR. The observed down-modulation of TRAIL and up-regulation of TNF and Fas transcripts might account for CD40-CD40L-mediated FL cell survival.

Antigens, CD↗
PubMed1998

Cloning and characterization of a novel form of tyrosine hydroxylase from the human parasite, Schistosoma mansoni.

Catecholamines such as dopamine and noradrenaline play important roles as neuromuscular transmitters and modulators in all parasitic helminths, including the human parasite, Schistosoma mansoni. We have cloned a novel S. mansoni tyrosine hydroxylase (SmTH) cDNA that shows high homology to mammalian tyrosine hydroxylase, the enzyme that catalyzes the first and rate-limiting step in the biosynthesis of catecholamines. Two subsets of SmTH transcripts were identified, one of which carries the S. mansoni spliced-leader (SL) sequence at its 5' end, whereas the other does not appear to be trans-spliced to the S. mansoni SL. The two types of SmTH transcripts encode the same protein of 465 amino acids and a predicted size of 54 kDa. Expression of SmTH as an N-terminal histidine fusion protein in Escherichia coli produced an active enzyme that was purified approximately 52-fold to apparent homogeneity and had a final specific activity of 0.78 micromol/min/mg. The purified enzyme was found to have the same absolute requirement for a tetrahydrobiopterin cofactor and the same sensitivity to inhibition by high concentrations of the substrate, tyrosine, as the mammalian enzyme. Purified SmTH also showed characteristic inhibition by catecholamine products, although the sensitivity to product inhibition was lower than that of the mammalian enzyme. This evidence indicates that SmTH encodes a functional tyrosine hydroxylase that has catalytic properties similar to those of the mammalian host's enzyme but may differ in its properties of regulation. This first demonstration of tyrosine hydroxylase in a parasitic helminth further suggests that the parasites have the enzymatic capacity to synthesize catecholamines endogenously.

Amino Acid Sequence↗
PubMed1998

The structure of somatosensory information for human postural control.

The goal of the present study was to determine the properties of the somatosensory stimulus that alter its temporal coupling to body sway. Six standing subjects were tested while touching a metal plate positioned either directly in front of or lateral to the subject. In each condition, the plate moved 4 mm at 0.2 Hz in either the medial-lateral (ML) or anterior-posterior direction (AP). The results showed that coupling between body sway and touch plate movement was strongest when the touch plate moved in a direction along the longitudinal axis of the arm. Coupling strength was weaker when the touch plate moved perpendicular to the longitudinal axis of the arm. The results consistently show that a radial expansion stimulus was more effective than a lamellar-type stimulus at the fingertip. Moreover, somatosensory information from a surface is interpreted in terms of the orientation of the contact limb and the potential degrees of freedom available through its movement.

Adult↗
PubMed1998

Granulocyte-macrophage colony-stimulating factor in post-remission therapy of acute myeloid leukemia.

The impact on occult leukemia of GM-CSF as a sensitizing agent has not been studied. We treated 41 adult patients with de novo acute myeloid leukemia, 25 of whom achieved complete remission and were given 1 to 3 post-remission courses, each course including GM-CSF begun 4 days prior to chemotherapy and given until day 3. After a median follow-up of 32 months, the probability of remaining in continuous complete remission was 17% at 46 months. GM-CSF in this setting was not associated with an improved outcome, arguing against a priming effect.

Acute Disease↗
PubMed1997

Coupling of fingertip somatosensory information to head and body sway.

Light touch contact of a fingertip with a stationary surface can provide orientation information that enhances control of upright stance. Slight changes in contact force at the fingertip provide sensory cues about the direction of body sway, allowing attenuation of sway. In the present study, we asked to which extent somatosensory cues are part of the postural control system, that is, which sensory signal supports this coupling? We investigated postural control not only when the contact surface was stationary, but also when it was moving rhythmically (from 0.1 to 0.5 Hz). In doing so, we brought somatosensory cues from the hand into conflict with other parts of the postural control system. Our focus was the temporal relationship between body sway and the contact surface. Postural sway was highly coherent with contact surface motion. Head and body sway assumed the frequency of the moving contact surface at all test frequencies. To account for these results, a simple model was formulated by approximating the postural control system as a second-order linear dynamical system. The influence of the touch stimulus was captured as the difference between the velocity of the contact surface and the velocity of body sway, multiplied by a coupling constant. Comparison of empirical results (relative phase, coherence, and gain) with model predictions supports the hypothesis of coupling between body sway and touch cues through the velocity of the somatosensory stimulus at the fingertip. One subject, who perceived movement of the touch surface, demonstrated weaker coupling than other subjects, suggesting that cognitive mechanisms introduce flexibility into the postural control scheme.

Adult↗
PubMed1997

Candidemia in acute leukemia patients.

Fungal infections are an important cause of morbidity and mortality in patients with acute leukemia (AL). Candidemia, once rare, is now a common nosocomial infection because of the intensity of chemotherapy, prolonged neutropenia, administration of broad-spectrum antibiotics and use of central venous catheters (CVC). We retrospectively identified patients treated for AL from 6/86 to 6/95 who also had candidemia. We describe 28 patients (incidence 6.3%) with a median age of 39 years, 24 of whom were on remission induction and 4 on postremission chemotherapy. All patients had CVC and empiric antimicrobial therapy, 4 had been given prophylactic antifungal drugs, and 2 had parenteral nutrition. Neutropenia was profound (median leukocyte nadir 200/microliters, median duration 19 days). Candida was isolated in blood cultures 10 days (median) after the start of neutropenia. The clinical presentation included fever (100%), respiratory symptoms (71.4%), skin lesions (39.2%) and septic shock (17.8%). Amphotericin B was given to 17 patients and liposomal amphotericin to 5 patients. Infection resolved in 18 patients (64.2%). 10 of whom were in complete remission. Mortality from candidemia was 17.8% (5/28). In conclusion, fungal infections are responsible for death in a significant number of patients. In our series treatment success was related to its rapid onset and to the recovery of neutropenia.

Acute Disease↗
PubMed1997

[Tuberculosis lymphadenitis in slaughtered swine from the State of São Paulo, Brazil: microscopic histopathology and demonstration of mycobacteria].

INTRODUCTION: As the occurrence of tuberculosis lymphadenitis in swine constitutes a public health risk, especially in immunosuppressed individuals, the distribution of tuberculoid lesions and the presence of microbacteria in lymph nodes and hepatic and muscular tissue in swine for slaughter, in the State of S. Paulo, SP (Brazil), in the period from 1993 to 1994, were studied. MATERIAL E METHOD: Tuberculous lesions in 60 carcasses of swine, slaughtered at abattoirs during the period 1993-1994, were studied. When macroscopic lesions were observed, a representative sampling of lymph nodes, hepatic and muscular tissues (masseter and diaphragm) were examined using histopathological and microbacterial isolation techniques. RESULTS: The macroscopic lesions were found predominantly in mesenteric lymph nodes. The MAI Complex (M.avium-intracellulare) was isolated mainly in the carcass group that showed lesions and was not found in the control group. Microorganisms of the MAI Complex were not isolated from hepatic and muscular tissues. CONCLUSION: No clear relationship between the type of mycobacteria isolated and the macroscopic lesions observed during the carcass inspection was found.

Animals↗
PubMed1997

[Scleredema, acanthosis nigricans and IgA/Kappa multiple myeloma].

BACKGROUND: Scleredema is an uncommon disease of unknown origin. Characteristic thick skin with symmetrical diffuse induration develops. The infiltration begins on the face and neck then extends to the root of the upper limbs and trunk. There are three clinical types of scleredema. The first is preceded by an upper airway infection and progresses rapidly before regressing spontaneously within a few months. The second type is associated with chronic diabetes. The third type is associated with monoclonal gammapathy, rarely of myelomatous type, and develops insidiously. Acanthosis nigricans can be a paraneoplastic syndrome, often associated with a gastrointestinal cancer. Few cases associating scleredema and acanathosis nigricans have been reported. CASE REPORT: A 56-year old woman had developed scleredema over the last 6 years when acanthosis nigricans appeared together with IgA kappa multiple myeloma. Treatment with melphalan and prednisolone was effective against the myeloma as well as the scleredema and acanthosis nigricans. DISCUSSION: Only five cases of associated scleredema and multiple myeloma have been reported, four with kappa IgG myeloma and one with IgA myeloma. An association between acanthosis nigricans and sclerederma could be coincidental although the fact that the different manifestations regressed together after the myeloma treatment would suggest some relationship between these three diseases.

Acanthosis Nigricans↗
PubMed1996

pS2 protein expression in gastric carcinoma. An immunohistochemical and immunoradiometric study.

The aim of this study was to examine the prevalence of pS2 expression in gastric carcinoma and to determine its prognostic significance. We analysed pS2 protein expression in 50 gastric carcinomas and respective adjacent mucosas by immunohistochemistry and immunoradiometric assay (IRMA). pS2 was consistently expressed in superficial and foveolar epithelium of non-neoplastic mucosa and in 66.0% of the carcinomas. pS2 immunoreactivity was significantly higher in diffuse than in intestinal carcinomas, and in those cases with nodal metastases than in those without. No correlation was found between pS2 immunostaining and gender, age, staging, depth of wall penetration, venous invasion, ploidy and S-phase fraction. The mean levels of pS2 (IRMA) were significantly lower in gastric carcinomas than in non-neoplastic mucosas, and were not correlated with any of the aforementioned clinicopathological features. The survival of patients with pS2-positive tumours was not significantly different from that of patients with pS2-negative tumours. We conclude that pS2 expression, which can be used as a marker of gastric-type differentiation, is associated with gastric carcinoma of diffuse type. The lack of correlation between pS2 expression and most features of tumor aggressiveness and patients' survival precludes its use as a prognostic tool in gastric carcinoma.

Adenocarcinoma↗
PubMed1996

Aortic coarctation with two intercostal aneurysms, appearing radiographically as a subclavian aneurysm. A case report.

The authors present a case of adult aortic coarctation with two associated intercostal aneurysms and poor left ventricular function. The intercostal aneurysms appear, radiographically, as a subclavian aneurysm. The case illustrates, in aortic coarctation, the potential difficulty in defining the anatomy of the associated vascular aneurysms. The authors also demonstrate that the left ventricular function markedly improves after resection of the aortic coarctation.

Aneurysm↗
PubMed1995

Immunophenotypic characteristics of acute leukaemia after myelodysplastic syndromes.

PURPOSE: To analyse the immunophenotype of acute leukaemia (AL) after myelodysplastic syndromes (MDS) (MDS-AL) and to compare the immunophenotypic profile of acute myeloblastic leukaemia (AML) secondary to MDS (MDS-AML) with that of "de novo"-AML. PATIENTS AND METHODS: Twenty patients with MDS-AL and 29 patients with "de novo"-AML were studied. Morphocytochemical and flow cytometric studies were done in each case. RESULTS: All the MDS-AL studied displayed a myeloid phenotype (MDS-AML). The main difference between MDS-AML and "de novo"-AML was a significantly higher frequency of CD34 expression in the first group. Differences concerning the expression of other non-lineage related or myeloid-associated markers were not statistically significant, although the percentage of cases CD15(+) was lower in MDS-AML. The overall frequency of expression of lymphoid-associated markers was similar in both groups, T-cell markers being more frequently detected. CONCLUSIONS: Our findings support the usefulness of immunophenotyping studies to characterize MDS-AL and suggest some immunophenotyping differences between MDS-AML and "de novo"-AML which might have biological and prognostic significance.

Adult↗
PubMed1994

Cloning and expression of rabbit and human brain tryptophan hydroxylase cDNA in Escherichia coli.

Rabbit and human brain tryptophan hydroxylase were cloned and expressed in Escherichia coli. Each of the respective cDNAs, including the complete coding sequence of tryptophan hydroxylase, was obtained by reverse transcription of rabbit or human brain mRNA and subcloned into the expression vector pET-3C. The expressed rabbit brain tryptophan hydroxylase activity, measured in the presence of tetrahydrobiopterin, represents approximately a 50-fold enhancement in yield (units/g tissue (wet wt) over that of a rabbit brain extract. Likewise, the level of expressed human brain tryptophan hydroxylase is approximately 57 times the average yield previously reported for a human brain homogenate and approximately 10-times the activity of homogenates of human raphe nucleus. The rabbit brain and pineal-derived tryptophan hydroxylase sequences varied by disparities in six amino acid residues (99% identity). The human carcinoid and brain peptide sequences varied by disparities in 18 amino acid residues (96% identity). Several properties of both expressed enzymes were studied and compared with those of native tryptophan hydroxylases.

Amino Acid Sequence↗