Search results for "SCID"
showing 10 items of 252 documents
Human interleukin-6 facilitates hepatitis B virus infection in vitro and in vivo.
2000
Abstract Background and aim. Research on hepatitis B virus (HBV) infection in vivo has been limited due to the absence of a suitable animal model. We have developed a human–mouse radiation chimera in which normal mice, preconditioned by lethal total body irradiation and radioprotected with SCID mouse bone marrow cells, are permissive for engraftment of human hematopoietic cells and solid tissues. This resulting human–mouse model, which comprises three genetically disparate sources of tissue, is therefore termed Trimera. This study was aimed at assessing the effect of human IL-6 on HBV infection in vivo in Trimera mice. Methods. Trimera mice were transplanted with human liver tissue fragment…
V gamma 9V delta 2 T lymphocytes efficiently recognize and kill zoledronate-sensitized, imatinib-sensitive, and imatinib-resistant chronic myelogenou…
2010
Abstract Imatinib mesylate (imatinib), a competitive inhibitor of the BCR-ABL tyrosine kinase, is highly effective against chronic myelogenous leukemia (CML) cells. However, because 20–30% of patients affected by CML display either primary or secondary resistance to imatinib, intentional activation of Vγ9Vδ2 T cells by phosphoantigens or by agents that cause their accumulation within cells, such as zoledronate, may represent a promising strategy for the design of a novel and highly innovative immunotherapy capable to overcome imatinib resistance. In this study, we show that Vγ9Vδ2 T lymphocytes recognize, trogocytose, and efficiently kill imatinib-sensitive and -resistant CML cell lines pre…
Focusing on Ciona intestinalis (Tunicata) innate immune system. Evolutionary implications
2009
Phylogenetic analyses based on molecular data provide compelling evidence that ascidians are of critical importance for studying chordate immune system evolution. The Ciona intestinalis draft genome sequence allows searches for phylogenetic relationships, gene cloning and expression of immunorelevant molecules. Acidians lack of the pivotal components of the vertebrate recombinatory adaptive immunity, i.e., MHC, TCRs and dimeric immunoglobulins. However, bioinformatic sequence analyses recognized genic elements indicating the essential features of the Ig superfamily and ancestor proto-MHC genes, suggesting a primitive pre-duplication and pre-recombination status. C. intestinalis genes for in…
Mutant HRAS as novel target for MEK and mTOR inhibitors.
2015
HRAS is a frequently mutated oncogene in cancer. However, mutant HRAS as drug target has not been investigated so far. Here, we show that mutant HRAS hyperactivates the RAS and the mTOR pathway in various cancer cell lines including lung, bladder and esophageal cancer. HRAS mutation sensitized toward growth inhibition by the MEK inhibitors AZD6244, MEK162 and PD0325901. Further, we found that MEK inhibitors induce apoptosis in mutant HRAS cell lines but not in cell lines lacking RAS mutations. In addition, knockdown of HRAS by siRNA blocked cell growth in mutant HRAS cell lines. Inhibition of the PI3K pathway alone or in combination with MEK inhibitors did not alter signaling nor had an imp…
A coupled discontinuous Galerkin-Finite Volume framework for solving gas dynamics over embedded geometries
2021
Author(s): Gulizzi, Vincenzo; Almgren, Ann S; Bell, John B | Abstract: We present a computational framework for solving the equations of inviscid gas dynamics using structured grids with embedded geometries. The novelty of the proposed approach is the use of high-order discontinuous Galerkin (dG) schemes and a shock-capturing Finite Volume (FV) scheme coupled via an $hp$ adaptive mesh refinement ($hp$-AMR) strategy that offers high-order accurate resolution of the embedded geometries. The $hp$-AMR strategy is based on a multi-level block-structured domain partition in which each level is represented by block-structured Cartesian grids and the embedded geometry is represented implicitly by a…
Über Carpus und Tarsus vonDeinotherium giganteum Kaup (Mamm., Proboscidea)
1962
Zusammengehorige Teile eines Skelettes vonDeinotherium giganteum Kp., welche im unteren Pliozan (Pontium) am Howenegg (Hegau, SW-Deutschland) ausgegraben worden sind, erlauben Beobachtungen zur Struktur des Hand- und Fusskelettes. Ein Verfahren zur graphischen Darstellung von Gelenkflachen wird geschildert, die Gultigkeit desCuvier’schen Korrelationsprinzips erortert.
Engraftment kinetics of human CD34+ cells from cord blood and mobilized peripheral blood co-transplanted into NOD/SCID mice
2004
We have reported short periods of post transplant neutropenia in human patients co-transplanted with cord blood (CB) and low numbers of haploidentical mobilized peripheral blood (MPB) CD34+ cells. To investigate the effect that the proportion of MPB to CB cells may have on engraftment kinetics, we have co-transplanted fixed numbers of human CB CD34+ cells mixed with different numbers of MPB CD34+ cells into NOD/SCID mice. We periodically quantified the proportion of human cells and the relative contribution of MPB and CB cells to the human engraftment on marrow aspirates. At the lowest MPB/CB ratios (5 : 1, 10 : 1), the contribution of CB cells predominated at all time points analyzed, and …
The effect of L-thyroxine on the metamorphosis of Ascidia malaca
1981
Larvae of Ascidia malaca, both before and after hatching, were treated with L-thyroxine solutions. The effect of the thyroid hormone was to induce the onset of metamorphosis and then to cause the rate at which body reorganization occurred to increase. In treated larvae the resorption of the tail occurred only few hours after hatching, and a beating heart appeared form 10 to 15 h earlier than in the control larvae. These results are discussed in the context of a probable relationship between the occurrence of a hormonal metamorphic factor and the button cells of the trunk.
Differential expression of mRNA encoding interleukin-12 p35 and p40 subunitsin situ
1994
Interleukin-12 (IL-12) is a heterodimeric cytokine that plays an important role in the regulation of the immune response. For biological activity the expression of both subunits of IL-12, p35 and p40, is required. Moreover, in the mouse the p40 chain of IL-12 specifically inhibits the effects of the IL-12 heterodimer. In the present study we have analyzed by in situ hybridization the expression of the p35 and p40 mRNA in the spleens of BALB/c and mutant (SCID, nude, beige) mice, unstimulated and after in vivo stimulation with lipopolysaccharide (LPS) and with staphylococcal enterotoxin B (SEB). In unstimulated spleens of BALB/c mice p35 and p40 mRNA were only detectable in a few strongly st…
Characterization and transcription studies of a phytochelatin synthase gene from the solitary tunicate Ciona intestinalis exposed to cadmium.
2014
The major thiol-containing molecules involved in controlling the level of intracellular ROS in eukaryotes, acting as a nonenzymatic detoxification system, are metallothioneins (MTs), glutathione (GSH) and phytochelatins (PCs). Both MTs and GSH are well-known in the animal kingdom. PC was considered a prerogative of the plant kingdom but, in 2001, a phytochelatin synthase (PCS) gene was described in the nematode Caenorhabditis elegans; additional genes encoding this enzyme were later described in the earthworm Eisenia fetida and in the parasitic nematode Schistosoma mansoni but scanty data are available, up to now, for Deuterostomes. Here, we describe the molecular characteristics and transc…