Search results for "MICE"

Insensitivity to Aβ42-lowering Nonsteroidal Anti-inflammatory Drugs and γ-Secretase Inhibitors Is Common among Aggressive Presenilin-1 Mutations

2007

Abeta42-lowering nonsteroidal anti-inflammatory drugs (NSAIDs) constitute the founding members of a new class of gamma-secretase modulators that avoid side effects of pan-gamma-secretase inhibitors on NOTCH processing and function, holding promise as potential disease-modifying agents for Alzheimer disease (AD). These modulators are active in cell-free gamma-secretase assays indicating that they directly target the gamma-secretase complex. Additional support for this hypothesis was provided by the observation that certain mutations in presenilin-1 (PS1) associated with early-onset familial AD (FAD) change the cellular drug response to Abeta42-lowering NSAIDs. Of particular interest is the P…

Helicobacter pylori gamma-glutamyl transpeptidase and vacuolating cytotoxin promote gastric persistence and immune tolerance

2013

Infection with the gastric bacterial pathogen Helicobacter pylori is typically contracted in early childhood and often persists for decades. The immunomodulatory properties of H. pylori that allow it to colonize humans persistently are believed to also account for H. pylori ’s protective effects against allergic and chronic inflammatory diseases. H. pylori infection efficiently reprograms dendritic cells (DCs) toward a tolerogenic phenotype and induces regulatory T cells (Tregs) with highly suppressive activity in models of allergen-induced asthma. We show here that two H. pylori virulence determinants, the γ-glutamyl transpeptidase GGT and the vacuolating cytotoxin VacA, contribute critic…

PAP/HIP protein is an obesogenic factor

2013

In this article we report the obesogenic role of the acute phase protein PAP/HIP. We found that the transgenic TgPAP/HIP mice develop spontaneous obesity under standard nutritional conditions, with high levels of glucose, leptin, and LDL and low levels of triglycerides and HDL in blood. Accordingly, PAP/HIP-deficient mice are skinny under standard nutritional conditions. We also found that expression of PAP/HIP is induced in intestinal epithelial cells in response to gavage with olive oil and this induction is AG490 sensitive. We demonstrated that incubation of 3T3-L1 preadipocytes with a low concentration as 1ng/ml of recombinant PAP/HIP results in accelerated BrdU incorporation in vitro. …

Interleukin-7 matures suppressive CD127(+) forkhead box P3 (FoxP3)(+) T cells into CD127(-) CD25(high) FoxP3(+) regulatory T cells.

2011

We have identified a novel interleukin (IL)-7-responsive T cell population [forkhead box P3 (FoxP3(+) ) CD4(+) CD25(+) CD127(+) ] that is comparably functionally suppressive to conventional FoxP3(+) CD4(+) CD25(+) regulatory T cells (T(regs) ). Although IL-2 is the most critical cytokine for thymic development of FoxP3(+) T(regs) , in the periphery other cytokines can be compensatory. CD25(+) CD127(+) T cells treated with IL-7 phenotypically 'matured' into the known 'classical' FoxP3(+) CD4(+) CD25(high) CD127(-) FoxP3(+) T(regs) . In freshly isolated splenocytes, the highest level of FoxP3 expression was found in CD127(+) CD25(+) T cells when compared with CD127(-) CD25(+) or CD127(+) CD25…

A Trans-amplifying RNA Vaccine Strategy for Induction of Potent Protective Immunity

2019

Here, we present a potent RNA vaccine approach based on a novel bipartite vector system using trans-amplifying RNA (taRNA). The vector cassette encoding the vaccine antigen originates from an alphaviral self-amplifying RNA (saRNA), from which the replicase was deleted to form a transreplicon. Replicase activity is provided in trans by a second molecule, either by a standard saRNA or an optimized non-replicating mRNA (nrRNA). The latter delivered 10- to 100-fold higher transreplicon expression than the former. Moreover, expression driven by the nrRNA-encoded replicase in the taRNA system was as efficient as in a conventional monopartite saRNA system. We show that the superiority of nrRNA- ov…

Erythropoietin and its lost receptor [8]

2007

Effects of pH and the presence of micelles on the resolution of diuretics by reversed-phase liquid chromatography

2004

A comparative study on the performance of two RPLC modes on the separation of 18 diuretics with diverse acid-base behaviour (acetazolamide, althiazide, amiloride, bendroflumethiazide, benzthiazide, bumetanide, canrenoic acid, chlorothiazide, chlorthalidone, ethacrynic acid, furosemide, hydrochlorothiazide, piretanide, probenecid, spironolactone, triamterene, trichloromethiazide and xipamide) was carried out. A conventional octadecylsilane column and acidic acetonitrile-water mobile phases, in the absence and presence of micelles of the anionic surfactant sodium dodecyl sulphate (SDS), were used. The effects of pH and the modifiers acetonitrile and SDS on peak asymmetry, efficiency, selectiv…

Chromatographic monitoring of diuretics in urine samples using a sodium dodecyl sulphate—propanol micellar eluent

1994

Abstract The effect of a varying pH, in the range 3−7, on the retention of several diuretics eluted with a sodium dodecyl sulphate (SDS) micellar mobile phase and with UV detection was studied. Significant changes in the capacity factors ( K′ of the diuretics bumetanide, ethacrynic acid, furosemide, probenecid and xipamide were observed. The protonation constants of these compounds were calculated from the k′ data. A study was also performed to select the optimum composition of the mobile phase (pH, concentration of SDS and nature and concentration of alcohol) for the separation of the above diuretics and the diuretics amiloride, bendroflumethiazide, chlorthalidone, hydrochlorothiazide, spi…

Chromatographic determination of diuretics in urine samples using hybrid micellar mobile phases with fluorimetric detection

1998

Abstract A rapid and simple chromatographic procedure, that uses hybrid micellar mobile phases of sodium dodecyl sulphate (SDS), propanol and phosphate buffer at pH 3, and fluorimetric detection ( λ exc =270 nm, λ em =430 nm), is reported for the determination of mixtures of seven diuretics of diverse efficacy (amiloride, bendroflumethiazide, bumetanide, furosemide, hydroflumethiazide, piretanide and triamterene), in urine samples. The application of a sequential optimization procedure for the resolution of the mixtures of the diuretics was problematic. However, their separation was achieved through the use of an interpretive optimization procedure based on the accurate description of the r…

African trypanosomes expressing multiple VSGs are rapidly eliminated by the host immune system

2019

Significance Many parasites escape the host immune system by undergoing antigenic variation, a process in which surface antigens are regularly shed and replaced by new ones. Trypanosoma brucei employs multiple sophisticated molecular mechanisms to ensure the expression of a homogeneous VSG coat. We generated a mutant parasite that expresses multiple distinct VSGs and studied the consequences of having a multi-VSG coat during an infection. We showed that expression of multiple VSGs makes the parasites more vulnerable to the immune response, which can now control the trypanosomes from the onset of the infection, allowing most mice to survive. In the future, trypanosome infections may be treat…