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1.  Markers of systemic inflammation predict survival in patients with advanced renal cell cancer 
British Journal of Cancer  2013;109(1):147-153.
The host inflammatory response has a vital role in carcinogenesis and tumour progression. We examined the prognostic value of inflammatory markers (albumin, white-cell count and its components, and platelets) in pre-treated patients with advanced renal cell carcinoma (RCC).
Using data from a randomised trial, multivariable proportional hazards models were generated to examine the impact of inflammatory markers and established prognostic factors (performance status, calcium, and haemoglobin) on overall survival (OS). We evaluated a new prognostic classification incorporating additional information from inflammatory markers.
Of the 416 patients, 362 were included in the analysis. Elevated neutrophil counts, elevated platelet counts, and a high neutrophil–lymphocyte ratio were significant independent predictors for shorter OS in a model with established prognostic factors. The addition of inflammatory markers improves the discriminatory value of the prognostic classification as compared with established factors alone (C-statistic 0.673 vs 0.654, P=0.002 for the difference), with 25.8% (P=0.004) of patients more appropriately classified using the new classification.
Markers of systemic inflammation contribute significantly to prognostic classification in addition to established factors for pre-treated patients with advanced RCC. Upon validation of these data in independent studies, stratification of patients using these markers in future clinical trials is recommended.
PMCID: PMC3708579  PMID: 23778526
inflammation; renal cell cancer; survival; prognosis; biomarker
2.  Occurrence of periodontal pathogens among patients with chronic periodontitis 
Brazilian Journal of Microbiology  2012;43(3):909-916.
The aim of the present study was to evaluate the presence of the periodontal pathogens that form the red complex (Tannerella forsythia, Porphyromonas gingivalis and Treponema denticola) and Aggregatibacter actinomycetemcomitans in patients with chronic periodontitis. The sample consisted of 29 patients with a clinical and radiographic diagnosis of chronic periodontitis based on the criteria of the American Academy of Periodontology (3). Samples for microbiological analysis were collected from the four sites of greatest probing depth in each patient, totaling 116 samples. These samples were processed using conventional polymerase chain reaction, which achieved the following positive results: 46.6% for P. gingivalis, 41.4% for T. forsythia, 33.6% for T. denticola and 27.6% for A. actinomycetemcomitans. P. gingivalis and T. forsythia were more prevalent (p < 0.05) in periodontal pockets ≥ 8 mm. The combinations T. forsythia + P. gingivalis (23.2%) and T. forsythia + P. gingivalis + T. denticola (20.0%) were more frequent in sites with a probing depth ≥ 8 mm. Associations with the simultaneous presence of A. actinomycetemcomitans + P. gingivalis, A. actinomycetemcomitans + T. forsythia, P. gingivalis + T. forsythia and T. forsythia + T. denticola were statistically significant (p < 0.05). It was concluded that the red complex pathogens are related to chronic periodontitis, presenting a higher occurrence in deep periodontal pockets. Moreover, the simultaneous presence of these bacteria in deep sites suggests a symbiotic relationship between these virulent species, favoring, in this way, a further progression of periodontal disease.
PMCID: PMC3768898  PMID: 24031906
periodontitis; pathogens; Tannerella forsythia; Porphyromonas gingivalis; Treponema denticola; Aggregatibacter actinomycetemcomitans
3.  Identification of Stylosanthes guianensis varieties using molecular genetic analysis 
AoB Plants  2012;2012:pls001.
Molecular genetic diversity and population structure analysis were used to clarify the controversial botanical classification of Stylosanthes guianensis. The accessions were clustered in nine groups, each of which was mainly composed of only one of the four botanical varieties.
Background and aims
The botanical classification of Stylosanthes guianensis is controversial, and few studies have used molecular markers to analyse this species. We used microsatellite markers to study the genetic diversity and population structure of S. guianensis and compare our results with the current infraspecific botanical classification.
A representative sample from the S. guianensis Brazilian germplasm collection (150 accessions) was analysed using 20 microsatellite loci. A model-based Bayesian approach implemented in the software STRUCTURE was used to assign accessions into clusters. A dendrogram was constructed based on Roger's genetic distances.
Principal results
The number of alleles per locus varied from 2 to 11, with an average of 4.7. The observed (HO) and expected (HE) heterozygosity values varied from 0 to 0.58 (mean of 0.18) and from 0.04 to 0.83 (mean of 0.55), respectively. Nine groups were assembled in STRUCTURE, and these groups were consistent with clusters inferred from the genetic distances and taxonomic varieties described for S. guianensis. The GST among the nine groups was 0.46.
The low HO and the GST values observed are in agreement with the outcrossing rate (26 %) estimated for this species. The data indicate a high genetic diversity among and within the botanical varieties and suggest that microsatellite-based information can be combined with classical taxonomy to elucidate infraspecific levels.
PMCID: PMC3292737  PMID: 22479672
4.  A mixed model QTL analysis for sugarcane multiple-harvest-location trial data 
Sugarcane-breeding programs take at least 12 years to develop new commercial cultivars. Molecular markers offer a possibility to study the genetic architecture of quantitative traits in sugarcane, and they may be used in marker-assisted selection to speed up artificial selection. Although the performance of sugarcane progenies in breeding programs are commonly evaluated across a range of locations and harvest years, many of the QTL detection methods ignore two- and three-way interactions between QTL, harvest, and location. In this work, a strategy for QTL detection in multi-harvest-location trial data, based on interval mapping and mixed models, is proposed and applied to map QTL effects on a segregating progeny from a biparental cross of pre-commercial Brazilian cultivars, evaluated at two locations and three consecutive harvest years for cane yield (tonnes per hectare), sugar yield (tonnes per hectare), fiber percent, and sucrose content. In the mixed model, we have included appropriate (co)variance structures for modeling heterogeneity and correlation of genetic effects and non-genetic residual effects. Forty-six QTLs were found: 13 QTLs for cane yield, 14 for sugar yield, 11 for fiber percent, and 8 for sucrose content. In addition, QTL by harvest, QTL by location, and QTL by harvest by location interaction effects were significant for all evaluated traits (30 QTLs showed some interaction, and 16 none). Our results contribute to a better understanding of the genetic architecture of complex traits related to biomass production and sucrose content in sugarcane.
Electronic supplementary material
The online version of this article (doi:10.1007/s00122-011-1748-8) contains supplementary material, which is available to authorized users.
PMCID: PMC3284670  PMID: 22159754
Polyploids; Outcrossing species; Integrated linkage map; QTL × E
5.  Quality of life in patients with advanced renal cell carcinoma treated with temsirolimus or interferon-α 
British Journal of Cancer  2010;102(10):1456-1460.
Temsirolimus was approved in Europe as first-line treatment of poor-prognosis advanced renal cell carcinoma (advRCC) based on significant clinical benefits.
Patients with advRCC and multiple poor-prognostic factors were randomly assigned to receive 25 mg intravenous temsirolimus weekly, interferon-α (titrated to 18 mU) three times weekly, or 15 mg intravenous temsirolimus weekly plus 6 mU of interferon-α three times weekly. EuroQol-5D utility score (EQ-5D index) and the EQ-5D visual analogue scale (EQ-VAS) responses were recorded. For analysis, patients were required to have their EQ-5D data recorded at baseline, week 12, and last visit after week 12. The analysis was conducted using last-visit data and a repeated-measures mixed-effect (RMME) model to evaluate quality-of-life differences between temsirolimus and interferon-α, controlling for baseline covariates.
Average EQ-5D score at the last measure was significantly higher in patients receiving temsirolimus compared with interferon-α: by 0.10 on EQ-5D index (P=0.0279) and by 6.61 on EQ-VAS (P=0.0095). In the RMME model, the least-square mean for on-treatment EQ-5D index score was 0.590 with temsirolimus and 0.492 with interferon-α (P=0.0022).
Temsirolimus is associated with significantly higher EQ-5D scores compared with interferon-α in patients with previously untreated poor-prognosis advRCC.
PMCID: PMC2869160  PMID: 20461090
interferon; quality of life; renal cell carcinoma; temsirolimus
6.  Expression of Xylella fastidiosa Fimbrial and Afimbrial Proteins during Biofilm Formation▿  
Applied and Environmental Microbiology  2010;76(13):4250-4259.
Complete sequencing of the Xylella fastidiosa genome revealed characteristics that have not been described previously for a phytopathogen. One characteristic of this genome was the abundance of genes encoding proteins with adhesion functions related to biofilm formation, an essential step for colonization of a plant host or an insect vector. We examined four of the proteins belonging to this class encoded by genes in the genome of X. fastidiosa: the PilA2 and PilC fimbrial proteins, which are components of the type IV pili, and XadA1 and XadA2, which are afimbrial adhesins. Polyclonal antibodies were raised against these four proteins, and their behavior during biofilm development was assessed by Western blotting and immunofluorescence assays. In addition, immunogold electron microscopy was used to detect these proteins in bacteria present in xylem vessels of three different hosts (citrus, periwinkle, and hibiscus). We verified that these proteins are present in X. fastidiosa biofilms but have differential regulation since the amounts varied temporally during biofilm formation, as well as spatially within the biofilms. The proteins were also detected in bacteria colonizing the xylem vessels of infected plants.
PMCID: PMC2897468  PMID: 20472735
7.  Recruitment of CD8+ T cells expressing granzymeA is associated with lesion progression in human cutaneous leishmaniasis 
Parasite immunology  2009;31(8):432-439.
Human infection with Leishmania braziliensis leads to the establishment of cutaneous leishmaniasis (CL), characterized by the appearance of skin lesions that progress from non-ulcerated to ulcerated forms. Our goal was to characterize the immunological kinetics associated with this progression, comparing the cellular composition, cytokines and granzyme expression between lesions of patients with early (E-CL) and late stages (L-CL) of CL. Histopathological analysis showed that lesions from L-CL had more exuberant inflammatory infiltrate as compared to E-CL. Although E-CL and L-CL lesions were predominantly mononuclear, lesions from E-CL patients presented higher neutrophil and eosinophil counts than L-CL. While percentages of CD4+ and of CD68+ cells were slightly higher in L-CL, a five-fold increase of CD8+ cells was observed in L-CL, as compared to E-CL. Moreover, CD8+ T-cells from L-CL expressed significantly higher levels of granzymeA than E-CL. Interestingly, granzymeA expression was positively correlated with intensity of the inflammatory infiltrate in L-CL but not E-CL. Lastly, percentages of IFN-γ+ and IL-10+ cells were higher in L-CL as compared to E-CL, with CD4+ T-cells and CD68+ monocytes as the main sources of these cytokines, respectively. These results suggest that recruitment of CD8+granzymeA+ T-cells is involved in lesion progression in human CL.
PMCID: PMC2764276  PMID: 19646207
leishmaniasis; lesion; progression; CD8+ T cells; granzyme
9.  Enhancement of the activity of phenoxodiol by cisplatin in prostate cancer cells 
British Journal of Cancer  2009;100(4):649-655.
Phenoxodiol is a novel isoflav-3-ene, currently undergoing clinical trials, that has a broad in vitro activity against a number of human cancer cell lines. Phenoxodiol alone inhibited DU145 and PC3 in a dose- and time-dependent manner with IC50 values of 8±1 and 38±9 μM, respectively. The combination of phenoxodiol and cisplatin was synergistic in DU145, and additive in PC3, as assessed by the Chou–Talalay method. Carboplatin was also synergistic in combination with phenoxodiol in DU145 cells. The activity of the phenoxodiol and cisplatin combination was confirmed in vivo using a DU145 xenograft model in nude mice. Pharmacokinetic data from these mice suggest that the mechanism of synergy may occur through a pharmacodynamic mechanism. An intracellular cisplatin accumulation assay showed a 35% (P<0.05) increase in the uptake of cisplatin when it was combined in a ratio of 1 μM: 5 μM phenoxodiol, resulting in a 300% (P<0.05) increase in DNA adducts. Taken together, our results suggest that phenoxodiol has interesting properties that make combination therapy with cisplatin or carboplatin appealing.
PMCID: PMC2653737  PMID: 19209173
isoflavones; prostate; DU145; signal transduction; Akt
13.  A rare case of benign isolated schwannoma in the inferior orbit 
Indian Journal of Ophthalmology  2008;56(6):514-515.
A rare case of unilateral orbital schwannoma arising from the infraorbital nerve is presented. An excision biopsy with complete removal of the mass in the inferior orbit was performed. A definitive diagnosis was made on histopathological examination. The clinical and histological features of schwannoma are discussed. A need for early removal of such tumors is recommended to prevent complications.
PMCID: PMC2612976  PMID: 18974528
Infraorbital; orbital; schwannoma
14.  Platinum(II) and Palladium(II) Complexes of Pyridine-2-Carbaldehyde Thiosemicarbazone as Alternative Antiherpes Simplex Virus Agents 
The cytotoxicity and the antivirus activity of Pd(II) and Pt(II) complexes with pyridine-2-carbaldehyde thiosemicarbazone (HFoTsc) against HSV replication were evaluated on four HSV strains—two wt strains Victoria (HSV-1) and BJA (HSV-2) and two ACVR mutants with different tk gene mutations R-100 (TKA, HSV-1) and PU (TKN, HSV-2). The experiments were performed on continuous MDBK cells and four HSV 1 and HSV 2 strains were used, two sensitive to acyclovir and two resistant mutants. The five complexes of HFoTsc, [Pt(FoTsc)Cl], [Pt(FoTsc)(H2FoTsc)]Cl2, [Pt(FoTsc)2], [Pd(FoTsc)(H2FoTsc)]Cl2, and [Pd(FoTsc)2], were found to be effective inhibitors of HSV replication. The most promising, active, and selective anti-HSV agent was found to be complex [Pt(FoTsc)(H2FoTsc)]Cl2. This complex could be useful in the treatment of HSV infections, since it is resistant to ACV mutants. PCR study of immediate early 300 bp ReIV Us1 region reveals that the complex [Pt(FoTsc)(H2FoTsc)]Cl2 specifically suppressed wt HSV-1 genome 2 hours after the infection, not inducing apoptosis/necrosis on the 8 hours after virus infection. The target was found to be most probably the viral, instead of the host cell DNA.
PMCID: PMC1876625  PMID: 17541481
15.  B Type natriuretic peptide: a good omen in myocardial ischaemia? 
Heart  2003;89(7):707-709.
PMCID: PMC1767724  PMID: 12807835
B type natriuretic peptide; BNP; cardiac remodelling; guanylyl cyclase; infarction; ischaemia; nesiritide
16.  An epidemiological study of sepsis in ICUs: Sepsis Brazil Study 
Critical Care  2006;10(Suppl 1):P111.
PMCID: PMC4092486
24.  Modes of mechanical ventilation in ICUs of Brazil 
Critical Care  2004;8(Suppl 1):P17.
PMCID: PMC4099604

Results 1-25 (31)