Niterói, Brazil
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Matthes T.,University of Geneva | Manfroi B.,Joseph Fourier University | Zeller A.,Medicine Faculty | Dunand-Sauthier I.,Medicine Faculty | And 3 more authors.
Leukemia | Year: 2015

Multiple myeloma (MM) invariably develops in the bone marrow (BM), indicating the strong requirement of this tumor for the peculiar BM microenvironment, rich in cytokine and hematopoietic precursor cells. Interleukin-6 (IL-6) and a proliferation inducing ligand (APRIL) are key cytokines implicated in MM development. Here, we show that MM cells changed the hematopoietic microenvironment early upon BM infiltration by strongly downregulating hematopoietic precursor cells from all lineages except myeloid precursor cells. Myeloid precursor cells constituted a major source of APRIL in MM-infiltrated BM, and their proliferative response to IL-6 upregulation explained their relative resistance to MM infiltration. The osteolytic molecule receptor activator of NF-kB ligand (RANK-L) expressed by MM cells started this myeloid proliferation by inducing in a contact-dependent manner IL-6 production by myeloid precursor cells themselves. Taken together, our data demonstrate that MM cells do not simply displace hematopoietic cells upon BM infiltration, but rather selectively modulate the BM microenvironment to preserve a pool of high APRIL-producing myeloid precursor cells. Our data also identify a positive regulation of APRIL by IL-6 in myeloid precursor cells. © 2015 Macmillan Publishers Limited All rights reserved.


Farage N.E.,Federal University of Fluminense | Stockler-Pinto M.B.,Federal University of Fluminense | Leal V.O.,Federal University of Fluminense | Cardozo L.L.,Federal University of Fluminense | And 3 more authors.
International Urology and Nephrology | Year: 2016

Purpose: This study aimed to evaluate the association among the expressions of pro- and anti-inflammatory nuclear factors (nuclear factor-kappaB, NF-κB and nuclear erythroid 2-related factor 2, Nrf2) and nutritional status in HD patients. Methods: This cross-sectional study included eighty-three HD patients. The peripheral blood mononuclear cells were isolated and processed for the evaluation of NF-κB and Nrf2 RNAm expression by quantitative real-time polymerase chain reaction. Muscle mass was estimated by creatinine index (CI) and percentage of body fat (%BF) by anthropometry. Seven-point subjective global assessment was also used to evaluate the nutritional status. Results: The NF-κB expression was negatively correlated with CI (r = −0.54, p = 0.0001), serum albumin (r = −0.32, p = 0.02) and %BF (r = −0.61, p = 0.001). Multiple linear regression analysis revealed that NF-κB expression was independently associated with CI (β: −0.8, p = 0.013) and %BF (β: −0.42, p = 0.04). There was no correlation among Nrf2 and anthropometric and biochemical variables. Conclusion: The classical NF-κB activation seems to be associated with poor nutritional status in HD patients; however, the exact underlying mechanisms deserve further studies. © 2016 Springer Science+Business Media Dordrecht


PubMed | Federal University of Fluminense, Medicine Faculty and Center Hopitalier Lyon Sud
Type: Journal Article | Journal: International urology and nephrology | Year: 2016

This study aimed to evaluate the association among the expressions of pro- and anti-inflammatory nuclear factors (nuclear factor-kappaB, NF-B and nuclear erythroid 2-related factor 2, Nrf2) and nutritional status in HD patients.This cross-sectional study included eighty-three HD patients. The peripheral blood mononuclear cells were isolated and processed for the evaluation of NF-B and Nrf2 RNAm expression by quantitative real-time polymerase chain reaction. Muscle mass was estimated by creatinine index (CI) and percentage of body fat (%BF) by anthropometry. Seven-point subjective global assessment was also used to evaluate the nutritional status.The NF-B expression was negatively correlated with CI (r=-0.54, p=0.0001), serum albumin (r=-0.32, p=0.02) and %BF (r=-0.61, p=0.001). Multiple linear regression analysis revealed that NF-B expression was independently associated with CI (: -0.8, p=0.013) and %BF (: -0.42, p=0.04). There was no correlation among Nrf2 and anthropometric and biochemical variables.The classical NF-B activation seems to be associated with poor nutritional status in HD patients; however, the exact underlying mechanisms deserve further studies.


News Article | November 11, 2016
Site: www.eurekalert.org

AURORA, Colo. (Nov. 10, 2016) - - Researchers, led by scientists at the University of Colorado School of Medicine, have found basic molecular processes used by the Zika virus to "hijack" the cells that it infects and potentially how it makes molecules that are directly linked to disease. The discovery, published in the journal Science, shows that a part of the Zika virus's RNA genome folds up into a complex structure and that this structure leads to the production of smaller RNAs that in related viruses are directly linked to disease. Viruses cannot reproduce on their own, they must infect cells and "hijack" the cell's biological machinery in order to make more copies of themselves. To do this, viruses use many molecular strategies. Zika is an example of a virus that does not store its genome in DNA, rather it uses a related molecule called the viral genomic RNA. Viruses related to Zika, such as West Nile and Dengue, are known to produce a set of smaller RNAs during infection (in addition to the long genomic RNA) that have been directly linked to disease. This process had not been explored with Zika virus until this study. The findings of this study show that Zika infection leads to the production of these smaller RNAs in several types of cells. The researchers show that part of the Zika genomic RNA "folds up" into a complex structure that interacts with and blocks a powerful cellular enzyme that normally destroys RNA, and the researchers used an advanced technique called x-ray crystallography to solve the structure of this folded-up RNA segment. By altering the Zika virus genomic RNA, the team was able to disrupt this structure and eliminate the production of the potentially disease-causing small RNAs. Jeffrey Kieft, PhD, professor of biochemistry and molecular genetics, led a team that consisted of scientists at the University of Colorado School of Medicine (Aurora, CO), the Advanced Light Source at the Lawrence Berkeley National Laboratory (Berkeley, CA), and the University of Texas Medical Branch (Galveston, TX). He is the corresponding author of the article, published in the journal Science. Benjamin Akiyama, PhD, a member of Dr. Kieft's Lab, was the lead author on the study. "The first step is stopping any process that causes disease is to understand that process in detail, preferably at the molecular level." said Dr. Kieft, who is also a member of the University of Colorado RNA BioScience Initiative. "Based on what we knew about related viruses, there was reason to suspect that Zika virus infection would result in potentially disease-causing RNAs, but we couldn't be sure. Now, having observed them and the molecular structures involved, we can ask new questions about the fundamental molecular processes Zika uses to take over a cell and cause disease." The findings could also inform ongoing efforts to develop a vaccine or other anti-Zika therapeutics. Also, because Zika is closely related to other dangerous viruses such as Dengue, West Nile, Japanese Encephalitis and Yellow Fever, the discoveries may be broadly applicable to understanding these viruses and may help in efforts to stop them. About the University of Colorado School of Medicine Faculty at the University of Colorado School of Medicine work to advance science and improve care. These faculty members include physicians, educators and scientists at University of Colorado Health, Children's Hospital Colorado, Denver Health, National Jewish Health, and the Denver Veterans Affairs Medical Center. The school is located on the Anschutz Medical Campus, one of four campuses in the University of Colorado system.


Matthes T.,University of Geneva | McKee T.,Medicine Faculty | Dunand-Sauthier I.,Medicine Faculty | Manfroi B.,Joseph Fourier University | And 4 more authors.
Leukemia | Year: 2015

Multiple myeloma (MM) is a non-curable tumor developing in the bone marrow (BM). The BM microenvironment rich in hematopoietic precursors is suspected to have a role in MM development. Here we show that a proliferation-inducing ligand (APRIL) mediated in vivo MM promotion. In MM-infiltrated BM, APRIL originated from differentiating myeloid cells with an expression peak in precursor cells. Notably, APRIL expression stayed stable in BM despite MM infiltration. The pool of APRIL-producing cells changed upon MM infiltration. Although CD16 + mature myeloid cells constituted about half of the APRIL-producing cells in healthy BM, CD16 - Elastase + myeloid precursor cells were predominant in MM-infiltrated BM. Myeloid precursor cells secreted all the APRIL they produced, and binding of secreted APRIL to MM cells, strictly dependent of heparan sulfate carried by CD138, resulted in an in situ internalization by tumor cells. This indicated APRIL consumption by MM in BM. Taken together, our data show that myelopoiesis dysregulation characterized by an increased proportion of precursor cells occurs in MM patients. Such dysregulation correlates with a stable expression of the MM-promoting factor APRIL in infiltrated BM. © 2015 Macmillan Publishers Limited All rights reserved.


PubMed | Medicine Faculty, University Hospital, University of Geneva, Joseph Fourier University and University of Basel
Type: Journal Article | Journal: Leukemia | Year: 2015

Multiple myeloma (MM) is a non-curable tumor developing in the bone marrow (BM). The BM microenvironment rich in hematopoietic precursors is suspected to have a role in MM development. Here we show that a proliferation-inducing ligand (APRIL) mediated in vivo MM promotion. In MM-infiltrated BM, APRIL originated from differentiating myeloid cells with an expression peak in precursor cells. Notably, APRIL expression stayed stable in BM despite MM infiltration. The pool of APRIL-producing cells changed upon MM infiltration. Although CD16(+) mature myeloid cells constituted about half of the APRIL-producing cells in healthy BM, CD16(-) Elastase(+) myeloid precursor cells were predominant in MM-infiltrated BM. Myeloid precursor cells secreted all the APRIL they produced, and binding of secreted APRIL to MM cells, strictly dependent of heparan sulfate carried by CD138, resulted in an in situ internalization by tumor cells. This indicated APRIL consumption by MM in BM. Taken together, our data show that myelopoiesis dysregulation characterized by an increased proportion of precursor cells occurs in MM patients. Such dysregulation correlates with a stable expression of the MM-promoting factor APRIL in infiltrated BM.


Behcet A.L.,University of Gaziantep | Kilic H.,Malatya State Hospital | Zengin S.,University of Gaziantep | Guler M.,University of Gaziantep | And 3 more authors.
Clinical and Applied Thrombosis/Hemostasis | Year: 2014

Purpose: The purpose of this study is to investigate the hispathological, biochemical, and clinical efficiency of Ankaferd Blood Stopper (ABS) in preventing postoperative intraabdominal adhesions. Method: A total of 40 Wistar albino species female rats were randomly separated into 4 groups. For the control group, 1 mL normal saline was administered; and for the second, third, and fourth groups 0.5, 1, and 2 mL, respectively, ABS was administered. Statistical analyses were evaluated with Tukey and analysis of variance test. Findings: Significant increase was observed in fibroblast and vascularization microscopically with increasing amount of ABS used. Degree of adhesion in the group administered with normal saline was lower compared to the other groups. Adhesion thickness and prevalence macroscopically increased with the increasing amount of ABS used in groups. Conclusion: It was determined in our study that ABS is not efficient in preventing intraabdominal adhesions; on the contrary, adhesions were increased with the increased amount of ABS used. © 2013 The Author(s).


Selma W.B.,University of Sousse | Harizi H.,University of Bordeaux Segalen | Bougmiza I.,Medicine Faculty | Hannachi N.,University of Sousse | And 3 more authors.
DNA and Cell Biology | Year: 2011

Interferon gamma (IFN-γ) is a key cytokine involved mainly in the defense against intracellular pathogens such as Mycobacterium tuberculosis. Given its key role in the control of tuberculosis (TB), in the present article we have investigated a possible association between IFN-γ gene single-nucleotide polymorphism linked to high and low producer phenotypes (IFN-γ [+874Thigh→Alow]) (rs2430561) and risk development of active TB in Tunisian patients. Genomic DNA samples were obtained from 223 patients with active TB (168 pulmonary and 55 extrapulmonary cases) and 150 healthy blood donors. Genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism method. The +874 AA genotype (low IFN-γ producer) was significantly associated with increased risk of developing of active pulmonary TB (odds ratio [OR]2.18; 95% confidence intervals [CI], 1.33-3.57; P corrected for the number of genotypes [Pc]0.003). By contrast, the AT genotype was found to be significantly associated with resistance to pulmonary TB (OR0.46; 95% CI, 0.28-0.74; Pc0.0018) and extrapulmonary TB development (OR0.46; 95% CI, 0.23-0.91; Pc0.045). Collectively, our data showed that the IFN-γ +874T/A polymorphism is a determinant in the resistance or susceptibility to the development of active TB in the studied population. © 2011 Mary Ann Liebert, Inc.


PubMed | Medicine Faculty and Federal University of Ceará
Type: Clinical Study | Journal: Acta cirurgica brasileira | Year: 2015

To assess the safety and potential equivalence of the use of hemosiderin compared to the Technetium-99 in sentinel lymph node biopsy in human breast cancer.Non-random sample of 14 volunteer women diagnosed with breast cancer with primary tumors (T1/T2) and clinically tumor-free axilla were submitted to the identification of sentinel lymph node using hemosiderin obtained from autologous blood injected in the periareolar region 24h before surgery on an outpatient basis. Patients received preoperative subareolar intradermal injection of Technetium-99 in the immediate preoperative period. Patients were submitted to sentinel lymph node biopsy, with incision in the axillary fold guided by Gamma-Probe, dissection by planes until the identification of the point of maximum uptake of Technetium-99, identifying the marked nodes and their colors. All surgical specimens were sent for pathological and immunohistochemical study.The results showed no evidence of side effects and/or allergic and non-allergic reactions in patients submitted to SLNB with hemosiderin. The SLN identification rate per patient was 100%. SLNB identification rate per patient with hemosiderin was the same as that of Technetium, with a concordance rate of 100% between the methods.Hemosiderin is a safe dye that is equivalent to Technetium in breast sentinel lymph node biopsy.


PubMed | Medicine Faculty
Type: Case Reports | Journal: Dermatology online journal | Year: 2010

A healthy, 5-year-old boy presented with cutaneous lesions on the right buttock, evident at birth. A physical examination revealed plugged pores in a linear distribution with the appearance of comedones and scar areas. Histopathological exam revealed multiple atrophic cystically dilated hair follicles containing abundant keratinous debris and small projections of epithelial cells extending from the wall of the cyst into the surrounding dermis, compatible with nevus comedonicus.

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