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Biomedical subjects

J G Oliveira

Publications and source records attributed to J G Oliveira.

16 recordsLinked to original sources

Degree-dependent intervertex separation in complex networks.

We study the mean length (l)(k) of the shortest paths between a vertex of degree k and other vertices in growing networks, where correlations are essential. In a number of deterministic scale-free networks we observe a power-law correction to a logarithmic dependence, (l)(k) = A ln[N/k((gamma-1)/2)]-Ck(gamma-1)/N+ in a wide range of network sizes. Here N is the number of vertices in the network, gamma is the degree distribution exponent, and the coefficients A and C depend on a network. We compare this law with a corresponding (l)(k) dependence obtained for random scale-free networks growing through the preferential attachment mechanism. In stochastic and deterministic growing trees with an exponential degree distribution, we observe a linear dependence on degree, (l)(k)approximately A ln N-Ck. We compare our findings for growing networks with those for uncorrelated graphs.

Journal Article↗

Brd4 is required for e2-mediated transcriptional activation but not genome partitioning of all papillomaviruses.

Bromodomain protein 4 (Brd4) has been identified as the cellular binding target through which the E2 protein of bovine papillomavirus type 1 links the viral genome to mitotic chromosomes. This tethering ensures retention and efficient partitioning of genomes to daughter cells following cell division. E2 is also a regulator of viral gene expression and a replication factor, in association with the viral E1 protein. In this study, we show that E2 proteins from a wide range of papillomaviruses interact with Brd4, albeit with variations in efficiency. Moreover, disruption of the E2-Brd4 interaction abrogates the transactivation function of E2, indicating that Brd4 is required for E2-mediated transactivation of all papillomaviruses. However, the interaction of E2 and Brd4 is not required for genome partitioning of all papillomaviruses since a number of papillomavirus E2 proteins associate with mitotic chromosomes independently of Brd4 binding. Furthermore, mutations in E2 that disrupt the interaction with Brd4 do not affect the ability of these E2s to associate with chromosomes. Thus, while all papillomaviruses attach their genomes to cellular chromosomes to facilitate genome segregation, they target different cellular binding partners. In summary, the E2 proteins from many papillomaviruses, including the clinically important alpha genus human papillomaviruses, interact with Brd4 to mediate transcriptional activation function but not all depend on this interaction to efficiently associate with mitotic chromosomes.

Animals↗

BeWo trophoblasts are unable to control replication of Toxoplasma gondii, even in the presence of exogenous IFN-gamma.

The ability of RH strain of Toxoplasma gondii to invade and grow into BeWo cells was investigated in the present study using IFN-gamma, l-tryptophan, or alpha-methyl-tryptophan treatments. HeLa cells were used in the same conditions for comparison purposes. It was demonstrated that BeWo cells are more permissive to T. gondii infection, making them more susceptible to this pathogen when compared to HeLa cells. Infection rates of BeWo cells do not show any significant alteration in different protocols using IFN-gamma. In addition, BeWo treated with l-tryptophan was unable to significantly increase parasite growth. In contrast, HeLa cells treated with IFN-gamma or IFN-gamma plus l-tryptophan are able to impair or increase, respectively, parasite replication, providing evidence that this indoleamine-2,3-dioxygenase-dependent phenomenon is operant in these cells, whereas it is inactive in BeWo. Therefore, our data support the hypothesis that the immunological mechanisms controlling infection at the maternal-fetal interface are different from those occurring in the periphery. At the same time that operating regulatory mechanisms work inside and outside the cells located at that microenvironment to prevent maternal rejection of the concept, these events might facilitate the progression of infection caused by intracellular pathogens, as T. gondii.

Animals↗

Inhomogeneous evolution of subgraphs and cycles in complex networks.

Subgraphs and cycles are often used to characterize the local properties of complex networks. Here we show that the subgraph structure of real networks is highly time dependent: as the network grows, the density of some subgraphs remains unchanged, while the density of others increase at a rate that is determined by the network's degree distribution and clustering properties. This inhomogeneous evolution process, supported by direct measurements on several real networks, leads to systematic shifts in the overall subgraph spectrum and to an inevitable overrepresentation of some subgraphs and cycles.

Journal Article↗

Salt sensitivity of blood pressure in patients with psoriasis on ciclosporin therapy.

BACKGROUND: Hypertension is one of the main side-effects of long-term therapy with ciclosporin. However, the influence of salt intake on the 24-h mean blood pressure of patients with psoriasis treated with ciclosporin is not known. OBJECTIVES: To evaluate, in patients with psoriasis, the sodium sensitivity of the ciclosporin-induced rise in blood pressure. METHODS: The 24-h ambulatory blood pressure was evaluated in 13 patients with psoriasis (age range 20-57 years) in two phases, before (phase I) and after the completion of 4 months of therapy with ciclosporin 3 mg kg(-1) daily (phase II). In both phases, the patients were studied in conditions of low sodium (LS) intake followed by a high sodium (HS) diet. RESULTS: Twenty-four-hour mean +/- SD blood pressure during LS and HS intake was, respectively, 86.3 +/- 1.6 mmHg and 85.5 +/- 1.8 mmHg during phase I, and 88.5 +/- 1.5 mmHg and 91.8 +/- 2.2 mmHg (P < 0.001 vs. phase I, HS; P < 0.05 vs. phase II, LS) during phase II. The median (interquartile range) sodium sensitivity index was greater during phase II than during phase I: - 0.0028 (- 0.0071 to 0.0009) vs. 0.0065 (- 0.0055 to 0.0258) (P < 0.02). The plasma levels and the daily urinary excretion of noradrenaline did not differ between phases I and II. CONCLUSIONS: The ciclosporin-induced rise in blood pressure is sodium sensitive. It is also suggested that sympathetic activation is not involved in the pathogenesis of ciclosporin-induced rise in blood pressure.

Adult↗

Antifungal activity of Ocimum gratissimum towards dermatophytes.

The development of more effective and less toxic antifungal agents is required for the treatment of dermatophytosis. Plants and their preparations have been used as medicines against infectious diseases. Extracts of Ocimum gratissimum leaves were investigated for in vitro antifungal activity, using agar dilution technique against dermatophytes. The extracts (hexane, chloroform fractions, the essential oil and eugenol) produced antifungal activities against Microsporum canis, M. gypseum, Trichophyton rubrum and T. mentagrophytes. Trichophyton rubrum, the most common aetiological agent of dermatophytosis in Goiânia, state of Goiás, Brazil, was also the most susceptible dermatophyte. The hexane fraction and eugenol were the most active. Hexane fraction inhibited the growth of 100% of dermatophytes at a concentration of 125 microg ml(-1), while eugenol inhibited the growth of 80% of dermatophytes at this same concentration. These results show that extracts of O. gratissimum are active in vitro against human pathogenic dermatophytes.

Antifungal Agents↗

Roughness of sandpile surfaces.

We study the surface roughness of prototype models displaying self-organized criticality (SOC) and their noncritical variants in one dimension. For SOC systems, we find that two seemingly equivalent definitions of surface roughness yield different asymptotic scaling exponents. Using approximate analytical arguments and extensive numerical studies we conclude that this ambiguity is due to the special scaling properties of the nonlinear steady state surface. We also find that there is no such ambiguity for non-SOC models, although there may be intermediate crossovers to different roughness values. Such crossovers need to be distinguished from the true asymptotic behavior, as in the case of a noncritical disordered sandpile model studied by Barker and Mehta [Phys. Rev. E 61, 6765 (2000)].

Journal Article↗

sTNFRI and sTNFRII synthesis by fine-needle aspiration biopsy sample cultures is significantly associated with acute rejection in kidney transplantation.

BACKGROUND: Previously we reported that cultures of fine-needle aspiration biopsy (FNAB) samples synthesize different cytokine pattern depending on the alloimmune response towards the kidney graft. However, we failed to find a clear picture for growth factors implicated in early T-cell activation (interferon-gamma, interleukin [IL]-4, IL-12), although we observed that interleukin-1 receptor antagonist (IL-1ra) was associated with absence of acute rejection. We have now studied tumor necrosis factor-alpha (TNF-alpha) and its two soluble receptors, sTNFRI and sTNFRII, IL-1beta and soluble IL-1 receptor II (sIL-1RII), and leukemia inhibitory factor (LIF), all potential modulators of T-cell activation. METHODS: Sixty-six cadaver kidney transplants (KTX) were divided into four groups: group 1, day 7 after KTX, stable (n=30); group 2, day 7 after KTX, 8+/-4.5 days before acute rejection (n=12); group 3, first day of acute rejection (n=17); and group 4, day 14 after KTX, stable (n=32). Patients from groups 1 and 4 remained rejection-free for the first 6 months. All rejection episodes were confirmed by core renal biopsy. FNAB samples were cultured according to our published methodology, and culture supernatants were collected at 48 hr and analyzed by ELISA for IL-1beta, sIL-1RII, TNF-alpha, sTNFRI, sTNFRII, and LIF. Serum levels for sIL-1RII, sTNFRI, and sTNFRII were also measured. RESULTS: FNAB cultures from groups 1 and 4 synthesized significantly lower amounts of sTNFRI and sTNFRII than those from either groups 2 or 3. Both sTNFRI and sTNFRII reached high positive and negative predictive values for acute rejection. IL-1beta and sIL-1RII were synthesized by all groups but without differences. No trace of LIF and TNF-alpha was found. sTNFRII was significantly higher in serum from group 3. CONCLUSIONS: Both TNF receptors were positively associated with acute rejection and were good predictors of impending acute rejection. The ratio of sIL-1RII over IL-1 (together with IL-1ra that we previously measured in FNAB cultures) suggests that IL-1 actions may be inhibited with current immunosuppression early after transplantation.

Acute Disease↗

Microemulsion cyclosporin formulation, in contrast to the old formulation, widens the T lymphocyte subsets differences between stable and acute rejection of kidney transplants.

BACKGROUND: The new cyclosporin (CsA) formulation, Neoral, has different pharmacokinetics compared with Sandimmune (SIM). Larger area under the curve (AUC) values with equivalent trough blood values are reached when Neoral is administered at equivalent doses to SIM. Previously, we showed a great diagnostic reliability when using cytofluorometric analysis from fine-needle aspiration biopsy (FNAB) samples. We investigated possible changes brought about by Neoral on lymphocyte subsets and the repercussions on the activation score cut-off for acute rejection, defined under SIM treatment. METHODS: Of 63 patients that received SIM, 40 remained rejection-free and 23 suffered one episode of rejection. Of 52 patients that received Neoral, 38 remained rejection-free. Peripheral blood lymphocytes (PBL) and lymphocytes from FNAB taken on days 7 and 14 post-transplantation and on the first day of acute rejection were analysed by flow cytometry. RESULTS: Trough blood CsA levels were not different between SIM and Neoral treatments. Among rejection-free patients, a significant down-regulation of CD3DR and of CD8DR expression on both graft-infiltrating lymphocytes (GIL) and PBL, and significant up-regulation of naïve T cells on GIL were observed with Neoral. These changes were followed by a significant down-regulation of the activation score with Neoral. Conversely, within the acute rejection group, the activation score was significantly higher with Neoral than with SIM. The activation score performed equally well in Neoral transplants compared with what we had reported with SIM. CONCLUSIONS: Our study indicates that Neoral elicits stronger immunosuppressive effects in stable patients, which eventually should translate into better clinical efficiency. However, when acute rejection supervenes, the treatment breakthrough seems stronger with Neoral. Cytofluorometric studies from FNAB samples showed that diagnostic reliability was maintained at a high level under Neoral therapy.

Antigens, CD↗

Comparison of virus isolation and various polymerase chain reaction methods in the diagnosis of mucocutaneous herpesvirus infection.

We compared two polymerase chain reaction (PCR) assays (simple and multiplex) and viral isolation to detect herpes simplex virus 1 (HSV-1) and varicella-zoster virus (VZV) in 15 clinical specimens from 13 patients with mucocutaneous herpetic infections. HSV-1 or VZV DNA was detected in 13 specimens by simple PCRs (HSV-1 or VZV PCR) and in 12 specimens by multiplex PCR. On the other hand, viral isolation was positive for 9 specimens only. The PCR protocols used in this study are not only more sensitive and faster than the traditional viral isolation and conventional PCR protocols but also can distinguish rapidly HSV-1 from VZV. We propose the PCRs described here for rapid and precise identification of etiological agents of mucocutaneous herpetic infections.

Adolescent↗

Analysis of fine-needle aspiration biopsies by flow cytometry in kidney transplant patients.

BACKGROUND: Peripheral blood lymphocyte (PBL) analysis by flow cytometry has been inconsistently reported as an adjunctive method for diagnosing acute kidney transplant rejection. However, there is good evidence that lymphocytes infiltrating renal grafts differ from those found at the peripheral level. We hypothesized that the study of aspiration biopsy samples in conjunction with PBL by flow cytometry would enable us to diagnose acute rejection crisis reliably. METHODS: Lymphocytes from PBL and aspiration biopsies of kidney transplant patients were analyzed. Fifty-one stable patients, rejection-free for the first 6 months, were studied on day 7 and day 30 after transplantation and were compared with 32 patients with 40 acute rejection episodes. RESULTS: Significant differences were observed for several lymphocyte subpopulations on aspiration biopsy samples comparing stable patients with rejection patients. In contrast, PBL analysis was not helpful in differentiating the two groups of patients. By combining the expression of several activation markers inside the graft with CD3DR and CD3CD25 aspiration biopsy to peripheral blood ratios, we obtained very good values for sensitivity and specificity-83.9% and 90.5%, respectively. The positive predictive value for rejection among dysfunctional grafts reached 85.8%. CONCLUSIONS: Flow cytometry study of aspiration biopsy samples of kidney transplant patients is a reliable and powerful method to diagnose acute rejection episodes, although it is needed to consider several lymphocyte phenotypes; cytofluorometric analysis of PBL is important because it provides graft-infiltrating cell to peripheral blood lymphocyte ratios. This safe and rapid test may significantly improve the management of kidney transplant patients.

Adolescent↗

Monocytes-macrophages and cytokines/chemokines in fine-needle aspiration biopsy cultures: enhanced interleukin-1 receptor antagonist synthesis in rejection-free kidney transplant patients.

BACKGROUND: Monocytes-macrophages are found within kidney allografts during the first days after surgery, where they perform "housekeeping" tasks, participate in postreperfusion injury, and act as antigen-presenting cells, as well as become involved in the effector phase of acute rejection. They also seem to play a prominent role in chronic rejection. We quantified their presence in fine-needle aspiration biopsies and studied the growth factors that, we hypothesized, would mark the different implications of the presence of monocytes-macrophages. METHODS: Fine-needle aspiration biopsies were obtained from 56 adult renal transplants and analyzed for CD14+ using the alkaline phosphatase-anti-alkaline phosphatase procedure. Thirty-three patients were studied on the production of interleukin (IL)-1 receptor antagonist (IL-1ra), IL-6, IL-8, macrophage colony-stimulating factor, monocyte chemotactic protein 1, and macrophage inflammatory protein 1alpha by aspiration biopsies cultures using enzyme-linked immunosorbent assay techniques. RESULTS: CD14+ cells were present at significantly higher numbers in steroid-resistant acute rejections but also during the first days after surgery, especially if acute tubular necrosis was present. We found a significantly higher production of IL-1ra by rejection-free patients compared with acutely rejecting patients, and this difference was already established on day 7 after surgery (10+/-10.5 days before rejection). CONCLUSIONS: Monocytes-macrophages are present at higher numbers in aspiration biopsies of kidney transplant patients suffering either acute tubular necrosis or steroid-resistant rejections, but they are present during the first days after transplant in stable patients, too. The production of IL-1ra is significantly up-regulated in stable patients, which suggests that monocytes-macrophages may constitute an early key factor in the down-regulation of the anti-allograft immune response.

Adolescent↗

Assessment of renal dopaminergic system activity during the recovery of renal function in human kidney transplant recipients.

BACKGROUND: The urinary excretion of free dopamine has been used as an index of the renal synthesis of amine. However, it is now well recognized that in the kidney, newly-formed dopamine is significantly inactivated through deamination to 3,4-dihydroxyphenylacetic acid (DOPAC) by monoamine oxidase (MAO). The aim of the present study was to assess the renal dopaminergic system activity during the recovery of renal function in kidney transplant recipients and to assess which parameters are appropriate for the evaluation of renal amine synthesis under these conditions. METHODS: Twenty-four-hour urinary excretion of L-DOPA, dopamine and its metabolites (DOPAC; 3-MT; HVA) were continuously monitored in 19 renal transplant recipients from the first day of surgery until the twelfth day post-transplantation. RESULTS: In 11 patients (Group 1), renal function consistently recovered throughout the study (plasma creatinine levels decreased from 6.2 +/- 0.4 to 2.1 +/- 0.1 mg/dl). Eight patients presented with acute tubular necrosis (Group 2) and minimal renal function was maintained until the twelfth post-operative day. The urinary excretion of L-DOPA did not differ throughout the study between the two groups of patients. In contrast, the 24-h urinary levels of dopamine, DOPAC and HVA were significantly higher throughout the study in patients of Group 1: dopamine (Group 1, 179 +/- 26 to 422 +/- 51 nmol/24 h; Group 2, 25 +/- 3 to 57 +/- 13 nmol/ 24 h), DOPAC (Group 1, 698 +/- 57 to 3487 +/- 414 nmol/ 24 h; Group 2, 158 +/- 22 to 1014 +/- 193 nmol/24 h) and HVA (Group 1, 13,058 +/- 1199 to 20,387 +/- 1559 nmol/ 24 h; Group 2, 4140 +/- 848 to 15,219 +/- 1037 nmol/24 h). CONCLUSIONS: The recovery of renal function in renal transplant recipients is accompanied by an enhanced ability to synthesize dopamine and inactivate it to DOPAC and HVA. It is suggested that the urinary levels of DOPAC may be a useful parameter for the assessment of dopamine formation in renal tissues.

3,4-Dihydroxyphenylacetic Acid↗

The low proliferation rates of human amniotic cells are neither associated to deregulated proto-oncogenes' expression nor to the effect of IFN alpha 2.

Primary cultures of human amniotic membrane (PCHAM) cells display very low proliferation rates while their doubling times vary between 150 h and 210 h even after mitogenic stimuli. However, the pattern of proto-oncogenes (c-fos, c-myc and c-jun) expression in these cells, upon serum restimulation, resembled that of cell lines that display shorter population doubling times. Serum stimulation of quiescent PCHAM cells promoted a rapid and transient c-fos mRNA expression, which was detected within 10 min, reached maximal levels at 30 min and decreased to undetectable levels 2-3 h later. The levels of c-myc or c-jun mRNA increased within 10 min after serum restimulation, peaked at 3 h and decreased to intermediate levels thereafter. We also present evidence showing that IFN alpha 2 treatment of PCHAM cells had no effect on their population doubling times nor in c-fas, c-myc, or c-jun mRNA expression, under conditions in which induction of IFN-stimulated genes, such as 2'-5' oligo-adenylate synthetase (OAS) and 6-16 was observed. We conclude that the growth constraints observed with this cells are not directly associated with a negative cellular growth regulation exerted by IFN alpha 2, nor due to a deregulated proto-oncogenes' expression.

Amnion↗