Physicochemical Properties of Seed Oil Blends and Their Potential for the Creation of Synthetic Oleosomes with Modulated Polarities.

There is an increasing demand within the pharmaceutical and cosmetic industries for biofriendly lipid-based active ingredient delivery systems. Micelles, liposomes, and lipid nanoparticles are currently the most used systems despite their limitations. Oleosomes, also known as lipid droplets, are promising alternatives to the existing strategies.

Small molecules to regulate the GH/IGF1 axis by inhibiting the growth hormone receptor synthesis.

Growth hormone (GH) and insulin-like growth factor-1 (IGF1) play an important role in mammalian development, cell proliferation and lifespan. Especially in cases of tumor growth there is an urgent need to control the GH/IGF1 axis. In this study we screened a 38,480-compound library, and in two consecutive rounds of analogues selection, we identified active lead compounds based on the following criteria: inhibition the GH receptor (GHR) activity and its downstream effectors Jak2 and STAT5, and inhibition of growth of breast and colon cancer cells.

The Identification of Small Molecule Inhibitors That Reduce Invasion and Metastasis of Aggressive Cancers.

Transformed epithelial cells can activate programs of epithelial plasticity and switch from a sessile, epithelial phenotype to a motile, mesenchymal phenotype. This process is linked to the acquisition of an invasive phenotype and the formation of distant metastases. The development of compounds that block the acquisition of an invasive phenotype or revert the invasive mesenchymal phenotype into a more differentiated epithelial phenotype represent a promising anticancer strategy.

Detection of mutant NPM1 mRNA in acute myeloid leukemia using custom gene expression arrays.

Mutations in the gene encoding nucleophosmin (NPM1) carry a prognostic value for patients with acute myeloid leukemia (AML). Various techniques are currently being used to detect these mutations in routine molecular diagnostics. Incorporation of accurate NPM1 mutation detection on a gene expression platform would enable simultaneous detection with various other expression biomarkers.

A standardized microarray assay for the independent gene expression markers in AML: EVI1 and BAALC.

High levels of BAALC, ERG, EVI1 and MN1 expression have been associated with shorter overall survival in AML but standardized and clinically validated assays are lacking. We have therefore developed and optimized an assay for standardized detection of these prognostic genes for patients with intermediate cytogenetic risk AML. In a training set of 147 intermediate cytogenetic risk cases we performed cross validations at 5 percentile steps of expression level and observed a bimodal significance profile for BAALC expression level and unimodal significance profiles for ERG and MN1 levels with no statistically significant cutoff points near the median expression level of BAALC, ERG or MN1.

Detection of CEBPA double mutants in acute myeloid leukemia using a custom gene expression array.

Double (bi-allelic) mutations in the gene encoding the CCAAT/enhancer-binding protein-alpha (CEBPA) transcription factor have a favorable prognostic impact in acute myeloid leukemia (AML). Double mutations in CEBPA can be detected using various techniques, but it is a notoriously difficult gene to sequence due to its high GC-content. Here we developed a two-step gene expression classifier for accurate and standardized detection of CEBPA double mutations.

Transcriptional control of MHC genes in fetal trophoblast cells.

Tight control of MHC expression is essential for the outcome of a successful pregnancy. The lack of MHC class II and class I mediated antigen presentation by fetal trophoblast cells is an important mechanism to evade maternal immune recognition. Interestingly, the deficient expression of MHC class II molecules (HLA-DR, -DQ and -DP) and of the classical MHC class I molecules HLA-A and HLA-B is also noted after IFN-gamma treatment in trophoblast-derived cell lines.

Survival of donor cells 25 years after intrauterine transfusion.

Persistence of donor leukocytes in the circulation of recipients of intrauterine transfusion (IUT) has been observed up to 5 years after birth. The aim of this study was to determine whether transfusions with nonirradiated, nonleukocyte-depleted donor blood during the fetal period resulted in long-term immunomodulation of the recipient. Twenty-four surviving IUT recipients between 1966 and 1976 were tested for autoimmune disease and autoantibodies at follow-up.

Lack of CIITA expression is central to the absence of antigen presentation functions of trophoblast cells and is caused by methylation of the IFN-gamma inducible promoter (PIV) of CIITA.

Lack of MHC-mediated antigen presenting functions of fetal trophoblast cells is an important mechanism to evade maternal immune recognition. In this study we demonstrated that the deficiency in MHC expression and antigen presentation in the trophoblast cell lines JEG-3 and JAR is caused by lack of class II transactivator (CIITA) expression due to hypermethylation of its interferon-gamma (IFN-gamma)-responsive promoter (PIV). Circumvention of this lack of CIITA expression by introduction of exogenous CIITA induced cell surface expression of HLA-DR, -DP, and -DQ, leading to an acquired capacity to present antigen to antigen-specific T cells.

Sweat testing in hypomelanosis of Ito: divergent results reflecting genetic heterogeneity.

Sweat testing using a modified version of the method described by Minor was performed in 5 children affected with hypomelanosis of Ito. In 4 cases the areas of hypopigmentation were arranged in patterns following the lines of Blaschko, whereas in one case a phylloid pattern was observed. In 4 cases the hypomelanotic areas were shown to be anhidrotic.

Immunological tolerance in an HLA non-identical chimeric twin.

Blood group chimeric twins offer a unique opportunity to study immunological tolerance in humans. Although this condition is not as rare as previously considered, detailed immunological studies of blood group chimeras are lacking. We describe here a case of secondary chimerism in a dizygotic twin of opposite gender.

Systemic sclerosis: new insights in autoimmunity.

The strong female predilection of systemic sclerosis, especially in women after their childbearing years, and the clinical and histopathological similarities with chronic graft-versus-host disease make systemic sclerosis an interesting subject of debate. Recent studies concerning the pathogenesis of this disease demonstrated the persistence of fetal cells in the maternal circulation in a majority of female patients. How or whether microchimerism is involved in the pathogenesis of systemic sclerosis remains to be elucidated.

Immunomodulation induced by intrauterine transfusions.

Intrauterine transfusion (IUT) therapy offers a unique model to study the immunological consequences of fetal exposure to donor alloantigens. IUT can result in immediate and short effects. Directly after IUT a relative leukocytosis was observed, which was evenly distributed among the different leukocyte subsets.

Intrauterine transfusions influence fetal leukocyte counts and subsets.

The objective of this study was to determine the effect of intravascular intrauterine transfusion (IUT) on fetal leukocyte counts and subsets. For this purpose, pre- and post-transfusion blood samples of 81 fetuses, receiving a total of 253 IUTs, were compared. Immediately after the IUT procedure an average decrease in fetal leukocyte count of 4 per cent was observed.

Intrauterine transfusions affect fetal T-cell immunity.

Intrauterine transfusion (IUT) therapy is the treatment of choice in severe hemolytic disease of the fetus. This treatment automatically implies the introduction of alloantigens in the fetal circulation, which might potentially influence the unprimed fetal immune system. The present study provides evidence that the fetal immune system is indeed prone to modulations of the T-cell receptor BV (TCRBV) repertoire as a result of IUT treatment.

Skewing of TCR V genes to CD4+ and CD8+ subsets of T lymphocytes is not determined by amino acid composition of CDR3.

TCR V genes show differing expression patterns, termed skewing, in CD4+ and CD8+ subsets of T lymphocytes. To determine which elements of the TCR V regions contribute to these observed TCR V gene skewing patterns, we have performed an in-depth analysis, taking advantage of RT-PCR and DNA sequencing, which was focused on the multi-member TCRBV6 gene family. These studies allowed us to evaluate the contributions of the various elements, that constitute the TCR beta chain variable region, to the observed TCR V gene skewing patterns.

Alterations in cord blood leukocyte subsets of patients with severe hemolytic disease after intrauterine transfusion therapy.

Objectives: The aim of this study was to compare, at delivery, the cord blood mononuclear cells of infants with severe hemolytic disease who received intrauterine transfusion (IUT) therapy with the cord blood mononuclear cells of healthy nonimmunized control neonates.

Study Design: The expression of leukocyte markers on CBMNC of 14 IUT-treated and 18 control neonates was analyzed by means of a panel of well-defined monoclonal antibodies and flow cytometry.

Results: Patients with severe hemolytic disease requiring IUT treatment displayed significant altered expression of some leukocyte markers when compared with control subjects.

Modulation of the T cell compartment by blood transfusion. Effect on cytotoxic and helper T lymphocyte precursor frequencies and T cell receptor Vbeta usage.

Recent data suggest that the favorable effect of pretransplant blood transfusion (BT) on transplant outcome depends on the HLA match. HLA-DR or haplotype shared transfusions lead to transplantation tolerance, and HLA-mismatched BT leads to immunization. The immunological mechanism involved is still unknown.

Antenatal care in pregnancies at risk of alloimmune thrombocytopenia: report of 19 cases in 16 families.

Objective: To assess accuracy of a management program in patients at risk for alloimmune thrombocytopenia (NAITP) and to describe perinatal outcomes.

Study Design: Nineteen fetuses at risk of thrombocytopenia were identified using obstetric history, HLA type of the mother and fetal phenotyping in cases where paternal heterozygozity for the offending antigen was present. Cordocentesis was timed according to obstetric history and performed with safety precautions to prevent haemorrhage.

Induction of additional red cell alloantibodies after intrauterine transfusions.

Background: The aim of this study was to determine the frequency and origin of additional alloantibodies directed against red cells (RBCs) after intrauterine transfusion (IUT).

Study Design And Methods: Between March 1987 and December 1992, fetuses with severe hemolytic disease (n = 91) received a total of 280 ultrasound-guided IUTs of RBCs from unrelated donors. The specificity of alloantibodies to RBCs in maternal serum was determined both before and after each IUT.

Specific recognition of staphylococcal enterotoxin A by human T cells bearing receptors with the V gamma 9 region.

T cells bearing the alpha beta receptor can specifically react with target cells coated with staphylococcal enterotoxin and expressing major histocompatibility complex class II molecules; these responses depend on which variable region (V) of the receptor's beta-subunit is used. We have now examined whether a similar situation exists for human T cells bearing the gamma delta receptor. We found that reactivity to staphylococcal enterotoxin A is strictly dependent on the presence of the V gamma 9 variable region in the gamma delta T-cell receptor (TCR).

Gamma delta T-cell receptor repertoire in human peripheral blood and thymus.

T-cell clones expressing the gamma delta T-cell receptor (Tcr) were generated from peripheral blood lymphocytes (PBLs) and from a thymus sample. In the panel of ten thymus-derived clones, four gamma delta Tcr phenotypes [as defined by the reaction of monoclonal antibodies (mAbs) directed against known V gamma and V delta regions] were identified. All the clones lacked expression of the V delta 3 V region, while seven clones were V delta 1+.

Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. XIV. Carrier requirement for suppressor cell induction.

The carrier requirements for the induction of helper and suppressor T (Ts) cells were compared. Although H-2-linked Ir genes control the development of helper T cells and hapten-specific B cells, they do not influence Ts3 generation. That is, GL phi nonresponder C57BL/6 mice can generate NP-specific Ts3 cells after priming with NP-GL phi.