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R Medeiros

Publications and source records attributed to R Medeiros.

At least 19 recordsLinked to original sources
PubMed2006

Dopamine D2 receptor polymorphisms in inflammatory bowel disease and the refractory response to treatment.

Dopamine and its receptors may be involved in inflammatory reaction. The availability of this molecule depends on its receptors. The DRD2 gene, which codifies for the D2 dopamine receptor, has several polymorphisms. In this study, the DRD2 TaqIA polymorphism, which confers a decreased receptor density, was evaluated in 313 individuals including 220 inflammatory bowel disease patients (143 patients with Crohn's disease and 77 with ulcerative colitis) and in 93 healthy blood donors. The analysis was carried out by PCR-RFLP techniques. The frequencies of A (1) A (1) and A (2) A (2) genotypes were similar among Crohn's disease, ulcerative colitis patients, and health controls. Also, the genotype frequency was similar in different groups of disease localization, behavior, and age of disease onset. However, the Crohn's disease patients carriers of A (2) A (2) genotype showed a lower risk for development refractory Crohn's disease (37 out 65) than A (1) A (1) and A (1) A (2) carriers (28 out of 65) [(OR=0.4, 95% CI 0.21-0.87; p=0.02)]. Our results support an involvement of the dopamine receptor in inflammatory bowel disease and suggest a new potential target for therapy in refractory Crohn's disease patients.

Adolescent↗
PubMed2006

The link between obesity and prostate cancer: the leptin pathway and therapeutic perspectives.

Obesity-associated prostate cancer (PCa) remains controversial, although most studies rely on body mass index evaluation, which is an indirect measure of fatness. Studies using body fat measurement and disease stratification according to PCa stage found stronger associations between obesity and PCa. Leptin is a pleiotrophic hormone mainly synthesized by adipocytes that acts in peripheral organs such as the prostate. This article reviews obesity-associated leptin's pathophysiological role in PCa progression. PCa development results from some known risk factors. Currently, there is enough evidence suggesting that leptin is an additional factor involved in advanced PCa occurrence, and obesity association with high-grade disease. Life-long exposure to genetic and/or environmental susceptibility factors that predispose to obesity and higher leptin levels may increase the risk for advanced PCa.

Chemoprevention↗
PubMed2005

The influence of smoking and other cofactors on the time to onset to cervical cancer in a southern European population.

Cervical cancer is a complex and multifactorial disease. Although there are substantial data supporting the causative role of persistent human papillomavirus (HPV) infection in the development of cervical cancer, the complete course of the disease has never been completely understood. Several risk cofactors have been suggested with controversial results. Portugal has the highest incidence of squamous cell carcinoma (SCC) within western Europe and there are no known studies regarding the role of cofactors in SCC. The aim of our study was to evaluate the role of smoking, sexual behaviour, reproductive and contraceptive history, in the time-to-onset (TTO) of severe cervical lesions (HGSIL/SCC) in the Portuguese population. We verified that age of first sexual intercourse under 18 years (odds ratio (OR) 2.8), pregnancy (OR 2.9), first pregnancy under 21 years (2.6), number of pregnancies (OR 2.3-5.4) and parity (OR 1.9-5.7) are risk factors in the development of cervical neoplasia. Smoke exposure index (SEI) was significantly different (P=0.002) between cases and controls. Our results regarding time-to-onset demonstrate that smoking (P<0.001, log rank test), number of sexual partners (P<0.001, log rank test) and use of oral contraceptives (P<0.001, log rank test) are important determinants in the earlier onset of severe cervical lesions. Using this approach, our findings may help to clarify the role of smoking and other cofactors in the persistence and progression of cervical lesions.

Adolescent↗
PubMed2005

Characterization of HPV genotype profile in squamous cervical lesions in Portugal, a southern European population at high risk of cervical cancer.

A different prevalence of human papillomavirus (HPV) types has been reported in distinct populations. Although Portugal has a relatively high incidence of cervical cancer within the European Union, no studies have been reported in the Portuguese population. Recently, a clinical trial using a vaccine targeted against HPV-16 demonstrated a high efficacy in preventing HPV-16 cervical lesions. The aim of the present study was the characterization of HPV genotype profile in squamous intraepithelial lesions (SIL) and invasive cervical cancer (ICC) from 608 patients using polymerase chain reaction (PCR) methodology. We frequently detected HPV-6/11 and HPV-16 in low-grade SIL (HPV-6/11, 18.9%; HPV-16, 44.2%). In high-grade SIL, HPV-16 was demonstrated in 74.2% of those lesions and in 80.0% of the cases with ICC. HPV-18 was found in 3.1%, 0.8% and in 15.0% of low, high SIL and ICC, respectively. The overall prevalence of multiple infections with high-risk HPV was 7.2%. Other types of HPV were detected in 7.0% of all cases. Our results demonstrate a high prevalence of HPV-16 in SIL and ICC in Portuguese women. Therefore, a prophylactic HPV-16/18 vaccine may be effective in the prevention of cervical cancer in a significant number of women from this southern European population.

Adult↗
PubMed2004

Binding of the hemagglutinin from human or equine influenza H3 viruses to the receptor is altered by substitutions at residue 193.

Interactions of the hemagglutinin (HA) of influenza viruses with sialic acids (SA) are important for host range restriction. Most human H3s have a Ser193, while avian and equine H3s usually have an Asn or a Lys, respectively. To investigate the role of residue 193 in the recognition of SA, substitutions were introduced by mutagenesis within a human H3 and an equine H3. Hemadsorption assays performed on COS-1 cells expressing wt or mutated HAs, showed that a K193S substitution in the context of an equine H3 decreased its ability to bind several animal erythrocytes. Using de- and then alpha2,3 or alpha2,6 re-sialylated chicken erythrocytes we showed that for both human and equine H3s, substitution of a Serine by positively-charged Arginine or Lysine at position 193 increased binding to its preferred receptor, SAalpha2,6Gal and SAalpha2,3Gal, respectively. Moreover, when combined with the L194I substitution, the S193R substitution induced binding of the human H3 to NeuAcalpha2,3Gal.

Amino Acid Substitution↗
PubMed2004

Leptin and prostate: implications for cancer prevention--overview of genetics and molecular interactions.

Leptin's relation with obesity has been clearly demonstrated while its role in oncobiology is still largely unknown. Epidemiological studies on serum leptin provide valuable though controversial data, while in vitro studies consistently show leptin's angiogenic and proliferative potential in cancer. Leptin's activity is mediated by tissue-specific receptors, differentially expressed in organs such as the prostate. The molecular cascades triggered by leptin result in prostatic cell proliferation and angiogenic activity, thus linking the hormone mainly to prostate cancer prognosis. This review also addresses leptin's metabolic interactions with cytokines, growth factors or hormones, establishing perceptive pathways leading to carcinogenesis or prostate cancer progression and metastasis. Better understanding of these mechanisms may help in the development of new and more effective treatments for prostate cancer. The consolidation of leptin molecular genetics profile in prostate cancer patients may help to create susceptibility groups in normal individuals, facilitating a preventive dietary intervention or strategies for chemoprevention. We hypothesize that the balance between androgen and leptin levels may facilitate the increase in the ratio of androgen-independent prostate cancer cells to androgen-dependent cells in the tumour.

Cell Transformation, Neoplastic↗
PubMed2004

HER2 polymorphism and breast cancer risk in Portugal.

Breast cancer is a major public health problem around the world, and its carcinogenesis is not yet well understood. The human epidermal growth factor Receptor 2 (HER2) seems to play an important role in the development of this neoplasia, and genetic alterations in this gene, such as point mutations and polymorphisms have been detected in breast cancer patients. We analysed the frequency of a single nucleotide polymorphism in the HER2 gene in blood samples from 152 breast cancer patients and 146 healthy controls using the polymerase chain reaction methodology, followed by restriction fragment length polymorphism (PCR-RFLP). We found a twofold increase in risk of breast cancer in women who are carriers of a Val allele genotype-Ile/Val and Val/Val genotypes [odds ratio (OR)=2.00; 95% confidence interval (CI) 1.23-3.25; P=0.005]. Our results indicate an association between the presence of the Val allele in the HER2 polymorphism and the risk of breast cancer. Further studies are needed to evaluate the role of this polymorphism in the behaviour of breast cancer.

Breast Neoplasms↗
PubMed2003

Association between CYP2E1 polymorphisms and susceptibility to prostate cancer.

Several genetic alterations have been associated with sporadic prostate cancer (PCa). In this study, the association between RsaI and DraI polymorphisms of CYP2E1 and PCa risk was analysed in a case-control study of 227 individuals using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Regarding DraI polymorphisms, the DD genotype is over-represented in PCa cases when compared with the control group (odds ratio (OR) 2.12; 95% confidence interval (CI) 1.11-4.05; P=0.022). Regarding the RsaI polymorphism, no significant differences were found. The results of this study indicate that DraI polymorphisms of the CYP2E1 gene may be associated with a twofold increased risk for the development of PCa.

Adult↗
PubMed2002

Endothelial nitric oxide synthase gene polymorphisms and genetic susceptibility to prostate cancer.

The endothelial cell-specific form of nitric oxide synthases (ecNOS) is localized at 7q35-q36 and is involved in vascular development and tumour growth in human prostate cancer. We have conducted a case-control study to investigate the prevalence of two polymorphisms at intron 4 (ecNOS4a/b) and exon 7 (Glu-Asp298) of ecNOS gene in 125 prostate cancer (PCa) patients and in 153 controls. We observed that the a-allele (aa or ab genotypes from ecNOS4a/b) was over-presented in the group of PCa with Gleason histological grade >or=7 (P=0.041). With regard to the Glu-Asp298 polymorphism, patients with the T-allele were younger than patients with no T-allele (P=0.037), and a statistically significant difference was noted in the Glu-Asp298 genotype distribution between cases with advanced disease and cases with localized disease (P=0.0013). When comparing cases and controls with logistic regression analysis we observed that the presence of the a-allele is associated with prostate cancer risk (odds ratio (OR) 1.83; 95% confidence interval (CI) 1.06-3.17; P=0.029), to high histological grade (Gleason >or=7) of PCa (OR 2.18; 95% CI 0.95-4.98; P=0.062) and with the risk of progression of the cancer disease (OR 2.85; 95% CI 1.19-6.82; P=0.018). Furthermore, we found that carriers with the combination of the a-allele (aa and ab ecNOS4a/b genotypes) and T-allele (GT and TT from Glu-Asp298) have a threefold increase in prostate cancer risk (OR 3.13; 95% CI 1.41-6.91, P=0.004). In summary, we have identified an NO-related genetic risk factor for prostate cancer that may help in understanding the molecular mechanism involved in the individual susceptibility to prostate cancer.

Adult↗
PubMed2001

Hemagglutinin residues of recent human A(H3N2) influenza viruses that contribute to the inability to agglutinate chicken erythrocytes.

To identify the molecular determinants contributing to the inability of recent human influenza A(H3N2) viruses to agglutinate chicken erythrocytes, phenotypic revertants were selected upon passage in eggs or MDCK cells. The Leu194Ile or Val226Ile substitutions were detected in their hemagglutinin (HA) sequence concomitantly with the phenotypic reversion. Remarkably, as little as 3.5% of variants bearing a Val226Ile substitution was found to confer the ability to agglutinate chicken erythrocytes to the virus population. Hemadsorption assays following transient expression of mutated HA proteins showed that the successive Gln226 --> Leu --> Ile --> Val changes observed on natural isolates resulted in a progressive loss of the ability of the HA to bind chicken erythrocytes. The Val226Ile change maintained the preference of the HA for SAalpha2,6Gal over SAalpha2,3Gal and enhanced binding of the HA to alpha2,6Gal receptors present on chicken erythrocytes. In contrast, simultaneous Ser193Arg and Leu194Ile substitutions that were found to confer the ability to agglutinate sheep erythrocytes increased the affinity of the HA for SAalpha2,3Gal.

Amino Acid Substitution↗
PubMed2001

The "in vivo" and "ex vivo" roles of cylcooxygenase-2, nuclear factor-kappaB and protein kinases pathways in the up-regulation of B1 receptor-mediated contraction of the rabbit aorta.

This study investigates some of the mechanisms involved in the up-regulation of the B1 receptor in the rabbit aorta. Pre-treatment of rabbit aorta with cyclooxygenase (COX) inhibitors 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsuphonyl) phenyl-2 (5H)-furanone (DFU), N-[2-cyclohexyloxy-4-nitrophenyl] methanesulfonamide (NS-398) or with indomethacin, but not with piroxicam, for 6 h, resulted in a significant inhibition of time-dependent contraction to the B1 selective agonist des-Arg9-Bradykinin (des-Arg9-BK), without affecting noradrenaline (NA) response. The kinase inhibitors bisindoylmaleimidine IX (RO 318220), staurosporine, genistein or tyrphostin B42 and the nuclear factor-kappaB (NF-kappaB) inhibitors pyrrolidinedithiocarbamate (PDTC), N(alpha)-p-tosyl-L-lysine chloro-methyl ketone (TLCK) or sulfasalazine, incubated for 6 h each, resulted in similar inhibition of des-Arg9-BK-induced contraction. When these inhibitors were pre-incubated for only 30 min, 6 h after setting up the preparations, sulfasalazine was the only drug tested that inhibited des-Arg9-BK-induced contraction, an effect which was reverted after the washing-out of the preparations. In preparations obtained from animals treated with lipopolysaccharide i.v. (LPS) 12 h prior, the up-regulation of B1 receptor in the aorta was markedly increased. The treatment of rabbits with PDTC, dexamethasone (Dexa), genistein or an association of subliminal doses of Dexa or with PDTC 12 h prior, which alone had no effect, all caused significant inhibition of des-Arg9-BK-induced contraction in the rabbit aorta. These results indicate that the time-dependent up-regulation of des-Arg9-BK-mediated contraction in the rabbit aorta involves the activation of protein kinase C, tyrosine kinase, through participation of COX-2 and the NF-kappaB transcription factor pathways.

Animals↗
PubMed1998

Neuroethologic differences in sleep deprivation induced by the single- and multiple-platform methods.

It has been proposed that the multiple-platform method (MP) for desynchronized sleep (DS) deprivation eliminates the stress induced by social isolation and by the restriction of locomotion in the single-platform (SP) method. MP, however, induces a higher increase in plasma corticosterone and ACTH levels than SP. Since deprivation is of heuristic value to identify the functional role of this state of sleep, the objective of the present study was to determine the behavioral differences exhibited by rats during sleep deprivation induced by these two methods. All behavioral patterns exhibited by a group of 7 albino male Wistar rats submitted to 4 days of sleep deprivation by the MP method (15 platforms, spaced 150 mm apart) and by 7 other rats submitted to sleep deprivation by the SP method were recorded in order to elaborate an ethogram. The behavioral patterns were quantitated in 10 replications by naive observers using other groups of 7 rats each submitted to the same deprivation schedule. Each quantification session lasted 35 min and the behavioral patterns presented by each rat over a period of 5 min were counted. The results obtained were: a) rats submitted to the MP method changed platforms at a mean rate of 2.62 +/- 1.17 platforms h-1 animal-1; b) the number of episodes of noninteractive waking patterns for the MP animals was significantly higher than that for SP animals (1077 vs 768); c) additional episodes of waking patterns (26.9 +/- 18.9 episodes/session) were promoted by social interaction in MP animals; d) the cumulative number of sleep episodes observed in the MP test (311) was significantly lower (chi-square test, 1 d.f., P < 0.05) than that observed in the SP test (534); e) rats submitted to the MP test did not show the well-known increase in ambulatory activity observed after the end of the SP test; f) comparison of 6 MP and 6 SP rats showed a significantly shorter latency to the onset of DS in MP rats (7.8 +/- 4.3 and 29.0 +/- 25.0 min, respectively; Student t-test, P < 0.05). We conclude that the social interaction occurring in the MP test generates additional stress since it increases the time of forced wakefulness and reduces the time of rest promoted by synchronized sleep.

Adrenocorticotropic Hormone↗
PubMed1997

Unrelated peripheral blood stem cell transplantation for Fanconi anemia.

The Brazilian unrelated bone marrow donor program began in 1993 and an unrelated matched donor was found for a Fanconi anemia patient without a sibling match. An 11-year-old female recipient received FTBI (6.0 Gy) and cyclophosphamide (40 mg/kg) as conditioning. The 41-year-old female unrelated donor received G-CSF at 5 micrograms/kg x 5 days, and on day 6 and 7 postmobilization, peripheral blood stem cells were harvested. Engraftment was seen on day 19 post-BMT and she remains alive and well on day 191+. This case supports the potential role of harvesting G-CSF-stimulated PBSC for unrelated bone marrow transplantation.

Child↗
PubMed1989

[Pulmonary arteriovenous fistula. A case report and review of the literature].

The aim of this paper is to review clinical and laboratory features of this unusual pathology and its complications, indicating transcatheter embolization as a first choice for its management. Our case report is of a seven year-old child, with complex pulmonary arteriovenous fistula of the anterior segment of right superior lobe, which was diagnosed mainly by cintilography and pulmonary angiogram. Clinically she had cyanosis, fatigue with exertion, clubbing of the fingers and polycythemia with low partial pressure of oxygen (PAO2: 68.1 mmHg; Sat O2: 92.4%; Hct: 47.5%; Hb: 16 gr%). She did not have Rendu-Osler-Weber disease. The anatomic structure and localization of the complex fistula was showed by cineangiographic study. We preferred to manage this fistula with transcatheter embolization with a 02 gauge stainless steel coil occluding device (Gianturco-Wallace), as it was single and the patient was too young for sustain surgical trauma and the outcome would be positively satisfactory. After the embolization cyanosis was relieved and we could see normal pulmonary circulation following the point of the pre-existing fistula. We concluded that a judicious assessment by cineangiography could help select the transcatheter embolization procedure as an attractive therapeutic approach instead of surgery.

Arteriovenous Fistula↗
PubMedDate not supplied

[Cryopreservation of bone marrow and peripheral blood stem cells using a controlled rate freezing system: experience with 86 procedures].

UNLABELLED: The cryopreservation of hematopoietic stem cells can be used for rescuing the hematopoiesis after high dose chemotherapy. PURPOSE: The ice crystal formation during the freezing procedure is the key point that can be harmful to the cells. The cryopreservation of hematopoietic stem cells in a controlled-rate freezer could decrease the cell damage. METHODS: Twenty-three patients with a median age of 26 years (range 03-57) had bone marrow and/or peripheral blood stem cells harvested from March 1993 through October 1994, ending up to 86 freezing procedures. The patient's diagnoses are as follows: Non-Hodgkin's Lymphoma (n = 5); Acute Myelogenous Leukemia (n = 8); Acute Lymphocytic Leukemia (n = 6); Hodgkin's disease (n = 3); Multiple Myeloma (n = 1). The cells were frozen away in a controlled-rate freezer chamber at the following rate: -1 degree C/min from room temperature to -45 degrees C and then, at -10 degrees C/min down to -80 degrees C. After freezing, the cells were kept into mechanical freezers until the marrow infusion. To mobilize PBSC (peripheral blood stem cells), G-CSF (granulocyte colony stimulating factor) was given. RESULTS: A median of 3.16 x 10(8) cells/kg (range 0.86-24.22) of PBSC and 2.03 x 10(8) cells/kg (0.19-12.21) of bone marrow cells were frozen. The median time to reach granulocytes greater than 500/microL and platelets greater than 20,000/microL was 12 days (range 8-40) and 31 days (range 8-80), respectively. All patients had marrow engraftment after infusion of hematopoietic stem cells. CONCLUSION: The cryopreservation procedure using a controlled-rate freezer can store hematopoietic stem cells and potentially, cause less damage to the cells.

Adolescent↗