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V Piguet

Publications and source records attributed to V Piguet.

47 records · Page 3Linked to original sources
PubMed1986

Heterogeneity of the induction of HLA-DR expression by human immune interferon on glioma cell lines and their clones.

The modulation of HLA-DR and HLA-A, -B, and -C by human recombinant immune interferon (IFN-gamma) was studied on 10 malignant glioma cell lines established in our laboratory, on 8 clones or subclones derived from these lines, and on a fetal astrocyte cell line. Comparative studies were performed with recombinant leukocyte interferon (IFN-alpha). The results not only confirmed the selective activity of IFN-gamma on the modulation of HLA-DR expression, as opposed to that of IFN-alpha, but also demonstrated a marked heterogeneity in the response of glioma cell lines and their clones to the two types of IFN tested. For example, all 3 clones of an inducible cell line could be modulated to express HLA-DR, whereas only 2 of 5 clones derived from a noninducible line were modulated. This heterogeneity did not seem to be due to the absence of the receptor for IFN-gamma on the surface of these cells, since almost all of the cell lines or clones tested (17 of 19) responded to IFN-gamma by the induction or enhancement of the expression for either HLA-DR or HLA-A, -B, and -C (or both). The heterogeneity of induction was also demonstrated between clones derived from a glioma line that did not express HLA-DR after IFN-gamma treatment. The production of HLA-DR by one of the clones was abundant enough to be confirmed by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis.

Antibodies, Monoclonal↗
PubMed1976

Myofibrillar ATPase, DNA and hydroxyproline content of human hypertrophied heart.

70 human hearts were studied less than 36 hours after death. The apex, and in some cases other parts of the myocardium were homogenized, DNA, hydroxyproline content, myofibrillar Ca2+ and Mg2+ ATPase were measured. In normal hearts the DNA and collagen content were 372 +/- 9 mg and 36 +/- 7 mg. Ca2+ and Mg2+ ATPase of the myofibrils prepared from these hearts have shown the same specific activity (35 +/- 5 and 34 +/- 6 nmol/min./mg) as those from fresh biopsies taken during open-chest surgery. The heart weight correlates with the DNA content (r= + 0.58 -p less than 0.01) and with the myofibrillar ATPase (r= - 0.33 - p less than 0.02) but not with the DNA concentration nor with the collagen content or concentration. The main result of this study was the presence of a negative correlation between the DNA content of the heart and the Mg2+ or Ca2+ myofibrillar ATPase (r= - 0.31, p less than 0.05 - r= - 0.45, p less than 0.01). This correlation was analysed with reference to the histological and biochemical studies published by several authors in human or experimental heart hypertrophy and it was suggested that in human heart hypertrophy the decrease of the myofibrillar or myosin ATPase is a direct consequence of the high degree of polyploidy of the muscular cells observed in this condition.

Adenosine Triphosphatases↗
PubMedDate not supplied

The Nef protein of primate lentiviruses.

The Nef protein of primate lentiviruses acts as an important virulence factor in vivo both in monkeys and in humans. Among a human cohort of long-term non-progressors, several Nef defective HIV1 viruses have been isolated, indicating that Nef may accelerate HIV progression and disease in humans. Additionally, a Nef-deleted SIV virus has low titres in rhesus monkeys and the animals develop AIDS at a much slower rate. In vitro, Nef can exert at least three kinds of effects: it downregulates CD4 and MHC class I, it stimulates virion infectivity and it alters signal transduction pathways. To accomplish this, Nef interacts with a series of cellular partners including CD4, components of the adaptor complexes AP-1 and AP-2, and several protein kinases, Nef often functioning as a connector between targets and effectors. The high degree of understanding of at least some aspects of Nef action, as well as the importance of this viral gene product for disease induction, identify Nef as a valuable target for the development of novel antiviral therapies. Moreover, the possibility of developing vaccines using attenuated viruses with deletions in nef and other crucial genes raises the possibility that the AIDS epidemic might one day be restrained.

Animals↗
PubMedDate not supplied

Transduction of CD34+ cells with lentiviral vectors enables the production of large quantities of transgene-expressing immature and mature dendritic cells.

BACKGROUND: Genetically engineered dendritic cells (DC) presenting specific antigens to T cells may be of great interest for immunotherapy. For this reason, the production of transgene-expressing DC derived from CD34 + cells transduced either shortly after ex vivo purification or during their differentiation into DC were evaluated. METHODS: CD34+ cells were transduced with lentivectors encoding for GFP before or after 21 days of culture with FLT3-ligand, thrombopoietin and stem cell factor and induction into DC with GM-CSF+IL-4 (G4) or G4+TNF (GT4). GFP and DC-specific marker expression was assessed by flow cytometry, and allostimulatory capacity was evaluated on GFP+ and GFP- sorted cells. RESULTS: Immature (G4-induced) DC obtained from amplified CD34 + cells were transducible by lentiviral vectors while mature (GT4-induced) DC were rather refractory. Moreover, since differentiated DC did not proliferate, large quantities of vectors were required to generate transgene-expressing cells with this protocol. In contrast, greater numbers of both immature and mature GFP- expressing DC were obtained with CD34+ cells exposed to lentivector shortly after purification. By the time of DC induction, GFP+ cells had increased by approximately 170-fold. After DC induction with G4, 32% of CD1a+, HLA-DR+, or CD40+ cells expressed GFP. CD1a+E-cadherin+ GFP+ Langerhans-like DC were also obtained. Incubation with TNF induced mature CD83+GFP+ DC that displayed a higher allostimulatory capacity than cells induced with G4 alone. CONCLUSION: The transduction of a small number of CD34+ cells with minimal doses of lentivector may allow for the production of a large number of DC expressing selected antigens useful for immunotherapy.

Antigens, CD↗
PubMedDate not supplied

Lack of effect of streptogramins on hepatic drug metabolism enzymes in the rat.

Male Sprague-Dawley rats were treated with streptogramin derivatives (RP 7293, RP 54476, RP 57669, and RP 59500) or with the macrolide troleandomycin. Liver cytosol and microsomes were prepared, and the in vitro transformation of several model substrates studied. Furthermore, total and complexed microsomal cytochrome P-450 levels were compared. Hepatic cytochrome P-450 metabolite complexes were detected 4 days after troleandomycin treatment (500 mg/kg/day po), whereas such effects were not observed with po RP 7293 (500 mg/kg/day, 4 days) or with iv RP 54476 (12 mg/kg/day, 7 days), RP 57669 (6 mg/kg/day, 7 days), or RP 59500 (6 and 18 mg/kg/day, 7 days). The administration of troleandomycin resulted in statistically significant increases in liver weight (+20%), microsomal protein (+70%), total cytochrome P-450 (+187%), and cytosolic glutathione S-transferase activity (+32%). The activities of aniline hydroxylase, aminopyrine N-demethylase, and the high and low phases of 7-ethoxyresorufin O-deethylase were markedly decreased by 36% to 56%. In contrast, none of these hepatic parameters was changed significantly after administration of each streptogramin. These results suggest that streptogramins have not, in contrast to many commonly used macrolide antibiotics, had potent or specific effects on hepatic drug metabolizing enzymes in rats.

7-Alkoxycoumarin O-Dealkylase↗