The role of micro-ribonucleic acids in normal hematopoiesis and leukemic T-lymphogenesis

Micro-ribonucleic acids (microRNAs) are small molecules containing 20-23 nucleotides. Despite their small size, it is likely that almost every cellular process is regulated by them. Moreover, aberrant microRNA expression has been involved in the development of various diseases, including cancer. Although many data are available about the role of microRNAs in various lymphoproliferative disorders, their impact on the development of acute lymphoblastic leukemia of T-cell progenitors is largely unknown. In this review, we present recent information about how specific microRNAs are expressed and regulated during malignant T-lymphopoiesis and about their role during normal hematopoiesis

Impact of endostatin gene therapy on myeloid-derived suppressor cells from a metastatic renal cell carcinoma

Aim: To evaluate the role of endostatin (ES) gene therapy on myeloid-derived suppressor cells (MDSC) in a metastatic model of renal cell carcinoma (RCC). Materials and Methods: Balb/C mice bearing orthotopic Renca tumors were treated with NIH/3T3LendSN or, as a control, with NIH/3T3-LXSN cells. At the end of in vivo experiment, plasma and tissue lung samples were collected. Plasma ES and granulocyte colony stimulating factor (G-CSF) levels were measured by ELISA and Milliplex, respectively. Quantification of CD11b⁺Gr⁻1⁺ cells and their subsets was performed by flow cytometry. Reactive oxygen species (ROS) production was measured in CD11b⁺Gr⁻1⁺ MDSC using the DCFDA marker by flow cytometry. Results: Metastatic RCC (mRCC) induced expansions of CD11b⁺Gr⁻1⁺ MDSC and promoted accumulation of these cells and their subtypes in lymphoid organ and metastases. ES treatment promoted low G-CSF plasmatic levels which were produced by the tumor microenvironment, reflecting the reduced metastatic accumulation of CD11b⁺Gr⁻1⁺ MDSC in the lungs. However, the therapy was selective for granulocytic cells, thus reducing the production of ROS. Conclusion: These findings confirm the expansion of MDSC during metastatic progression of RCC and indicate the important role of ES in reducing MDSC and possible use of ES therapy in combined anticancer treatment

Immunoparasitological Diagnosis Of Strongyloides Stercoralis In Garbage Collectors In Uberlândia, Mg, Brazil

The objective of this study was to determine the presence of Strongyloides stercoralis in urban garbage collectors through the use of immunological and parasitological methods. A total of 92 individuals were evaluated from August, 1997, to June, 1998. For the parasitological diagnosis Baermann and Lutz' methods were applied. The immunological diagnosis involved the indirect fluorescence antibody test (IFAT) and the enzyme-linked immunosorbent assay (ELISA) to detect specific IgG antibodies. Of the 92 workers examined, six (6.5%) were infected with larvae of S. stercoralis. The IFAT detected 19 (16.3%) and the ELISA 17 (18.5%) positive serum samples. The differences between the results of parasitological and immunological methods were statistically significant (p<0.05). These results demonstrate that there is a need to improve the health conditions of this category of city employees.6203/04/15180182CONCHA, R., HARRINGTON, J.R.W., ROGERS, A.L., Intestinal strongyloidiasis: Recognition, management and determinants of outcome (2005) J Clin Gastroenterol, 39, pp. 203-211SIDDIQUI, A.A., BERK, S.L., Diagnosis of Strongyloides stercoralis infection (2001) Clin Infect Dis, 33, pp. 1040-1047FERREIRA, M., Strongyloidiasis and acquired immunodeficiency syndrome (2003) Enf Emerg, 5, pp. 18-26VADLAMUDI, R.S., CHI, D.S., KRISHANASWAMY, G., Intestinal strongyloidiasis and hyperinfection syndrome (2006) Clin Mol Allergy, 4, pp. 1-13BAERMANN G. Eine Einfache methode zur auffindung von Ankylostomum (Nematoden) larven in Erdproben. Mededeel mit h. Geneesk Lab Weltvreden Feestbundel, Batavia, 1917, p. 41-7LUTZ, A.V., Schistosoma mansoni e a schistosomose, Segundo observações feitas no Brasil. (1919) Mem Inst Oswaldo Cruz, 11, pp. 121-125COSTA-CRUZ, J.M., BULLAMAH, C.B., GONÇALVEZ-PIRES, M.R.F., Cryo-microtome sections of coproculture larvae of Strongyloides stercoralis and Strongyloides ratti as antigen sources for the immunodiagnosis of human strongyloidiasis (1997) Rev Inst Med Trop São Paulo, 39, pp. 313-317MACHADO, E.R., UETA, M.T., GONÇALVES-PIRES, M.R.F., Strongyloides venezuelensis alkaline extract for the diagnosis of human strongyloidiasis by enzyme-linked immunosorbent assay (2003) Mem Inst Oswaldo Cruz, 98, pp. 849-853MACHADO, E.R., COSTA-CRUZ, J.M., Strongyloides stercoralis and other enteroparasites in children at Uberlândia City, state of Minas Gerais, Brazil (1998) Mem Inst Oswaldo Cruz, 93, pp. 161-164PAULA, F.M., CASTRO, E., GONÇALVES-PIRES, M.R.F., Parasitological and immunological diagnoses of strongyloidiasis in immunocompromised and nonimmunocompromised children at Uberlândia City, state of Minas Gerais, Brazil (2000) Rev Inst Med Trop São Paulo, 42, pp. 51-55OLIVEIRA, L.C.M., RIBEIRO, C.T., MENDES, D.M., Frequency of Strongyloides stercoralis in alcoholics (2002) Mem Inst Oswaldo Cruz, 97, pp. 119-121LINDO, J.F., CONWAY, D.J., ATKINS, N.S., Prospective evaluation of enzyme-linked immunosorbent assay and immunoblot methods for the diagnosis of endemic Strongyloides stercoralis infection (1994) Am J Trop Med Hyg, 51, pp. 175-179CLARK, C.S., LINNEMANN Jr, C.C., CLARK, J.G., Enteric parasites in workers occupationally exposed to sewage (1984) J Occup Med, 26, pp. 273-275SCHLOSSER, O., RALL, D., LAURECEAU, M.-N., Intestinal parasite carriage in workers exposed to sewage (1999) Eur J Epidemiol, 15, pp. 261-265GOMES, T.C., ALMEIDA, M.F., MUIRA, L.A., Helmintoses intestinais em população de rua da cidade do Rio de Janeiro. (2002) Rev Soc Bras Med Trop, 35, pp. 531-53

Dissecting kinetically coupled quintessence: phenomenology and observational tests

We investigate an interacting dark energy model which allows for the kinetic term of the scalar field to couple to dark matter via a power-law interaction. The model is characterised by scaling solutions at early times, which are of high interest to alleviate the coincidence problem, followed by a period of accelerated expansion. We discuss the phenomenology of the background evolution and of the linear scalar perturbations and we identify measurable signatures of the coupling in the dark sector on the cosmic microwave background, the lensing potential auto-correlation and the matter power spectra. We also perform a parameter estimation analysis using data of cosmic microwave background temperature, polarisation and lensing, baryonic acoustic oscillations and supernovae. We find that the strength of the coupling between the dark sectors, regulated by the parameter α, is constrained to be of order 10-4. A model selection analysis does not reveal a statistical preference between ΛCDM and the Kinetic model

Structure formation in binary colloids

A theoretical study of the structure formation observed very recently [Phys. Rev. Lett. 90, 128303 (2003)] in binary colloids is presented. In our model solely the dipole-dipole interaction of the particles is considered, electrohidrodynamic effects are excluded. Based on molecular dynamics simulations and analytic calculations we show that the total concentration of the particles, the relative concentration and the relative dipole moment of the components determine the structure of the colloid. At low concentrations the kinetic aggregation of particles results in fractal structures which show a crossover behavior when increasing the concentration. At high concentration various lattice structures are obtained in a good agreement with experiments.Comment: revtex, 4 pages, figures available from authors due to size problem

Orientational order in dipolar fluids consisting of nonspherical hard particles

We investigate fluids of dipolar hard particles by a certain variant of density-functional theory. The proper treatment of the long range of the dipolar interactions yields a contribution to the free energy which favors ferromagnetic order. This corrects previous theoretical analyses. We determine phase diagrams for dipolar ellipsoids and spherocylinders as a function of the aspect ratio of the particles and their dipole moment. In the nonpolar limit the results for the phase boundary between the isotropic and nematic phase agree well with simulation data. Adding a longitudinal dipole moment favors the nematic phase. For oblate or slightly elongated particles we find a ferromagnetic liquid phase, which has also been detected in computer simulations of fluids consisting of spherical dipolar particles. The detailed structure of the phase diagram and its evolution upon changing the aspect ratio are discussed in detail.Comment: 35 pages LaTeX with epsf style, 11 figures in eps format, submitted to Phys. Rev.

Inhalation of the prodrug PI3K inhibitor CL27c improves lung function in asthma and fibrosis

PI3K activation plays a central role in the development of pulmonary inflammation and tissue remodeling. PI3K inhibitors may thus offer an improved therapeutic opportunity to treat non-resolving lung inflammation but their action is limited by unwanted on-target systemic toxicity. Here we present CL27c, a prodrug pan-PI3K inhibitor designed for local therapy, and investigate whether inhaled CL27c is effective in asthma and pulmonary fibrosis. Mice inhaling CL27c show reduced insulin-evoked Akt phosphorylation in lungs, but no change in other tissues and no increase in blood glycaemia, in line with a local action. In murine models of acute or glucocorticoid-resistant neutrophilic asthma, inhaled CL27c reduces inflammation and improves lung function. Finally, inhaled CL27c administered in a therapeutic setting protects from bleomycin-induced lung fibrosis, ultimately leading to significantly improved survival. Therefore, local delivery of a pan-PI3K inhibitor prodrug reduces systemic on-target side effects but effectively treats asthma and irreversible pulmonary fibrosis