In vitro evidence for dose-dependent cytotoxicity as the predominant effect of low dose Ara-C on human leukemic and normal marrow cells

1989 ◽  
Vol 23 (2) ◽  
Author(s):  
ClaraS.P. Chan ◽  
GeraldineP. Schechter
Keyword(s):  
Low Dose ◽  
Dose Dependent ◽  
Predominant Effect ◽  
Marrow Cells

The effect of low dose ARA-C on in-vitro haemopoiesis of marrow cells from myelodysplastic patients

1987 ◽  
Vol 11 (4) ◽  
pp. 379-384 ◽  
Author(s):  
Arnon Nagler ◽  
Irena Riklis ◽  
Ilana Tatarsky ◽  
Ina Fabian
Keyword(s):  
Low Dose ◽  
Marrow Cells

Angiotensin II relaxation of rainbow trout vessels in vitro

1994 ◽  
Vol 266 (6) ◽  
pp. R1856-R1860 ◽  
Author(s):  
D. J. Conklin ◽  
K. R. Olson
Keyword(s):  
Angiotensin Ii ◽  
Effective Concentration ◽  
Partial Recovery ◽  
Ang Ii ◽  
Systemic Arch ◽  
Ventral Aorta ◽  
Dose Dependent ◽  
Large Vessels ◽  
Predominant Effect

The effects of salmonid angiotensin II ([Asn1,Val5]ANG II) were examined in isolated trout arteries [celiacomesenteric (CMA), coronary (COA), 3rd or 4th gill arch epibranchial (EBA), ventral aorta (VA)] and veins [anterior cardinal (ACV) and ductus Cuvier strips (DOC)]. ANG II (10(-10)-10(-6) M) produced modest (< 50% other agonists) transient contractions in otherwise unstimulated COA but was a poor agonist in other vessels. In precontracted vessels, ANG II responses were triphasic; transient contraction (P1), relaxation (P2), and partial recovery (P3) and vessel specific. P1 was similar to uncontracted vessels. With 10(-6) MANG II, %P2 was: EBA, 60.3 +/- 8.3% (n = 22); CMA, 48.8 +/- 8.8% (n = 4); ACV, 38.8 +/- 5.3% (n = 29); VA, 29.4 +/- 4.9% (n = 8); DOC, 25.5 +/- 2.4% (n = 14); COA, 13.2 +/- 6.7% (n = 4). P2 in EBA and ACV was dose dependent [EBA vs. ACV: mean effective concentration (EC50) = 3.6 x 10(-9) +/- 8.1 x 10(-10) M, n = 7 vs. 6.2 x 10(-8) +/- 2.3 x 10(-8) M, n = 8, respectively; P < or = 0.05] and inhibited by indomethacin but unaffected by propranolol, NG-monomethyl-L-arginine, saralasin, PD-123177, or DuP-753. Removal of EBA endothelium also inhibited relaxation. By comparison, ANG II did not relax bullfrog arteries (dorsal aorta, systemic arch, CMA) or femoral veins. These results show that, in large vessels of trout, the predominant effect of ANG II is an endothelium-dependent, prostanoid-mediated relaxation that is unaffected by classical ANG II-receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Dose-Dependent Sorafenib-Induced Immunosuppression Is Associated with Aberrant NFAT Activation and Expression of PD-1 in T Cells

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 681 ◽  
Author(s):  
Renuka V. Iyer ◽  
Orla Maguire ◽  
Minhyung Kim ◽  
Leslie I. Curtin ◽  
Sandra Sexton ◽  
...  
Keyword(s):  
T Cells ◽  
Low Dose ◽  
Growth Delay ◽  
High Dose ◽  
Dependent Manner ◽  
Sorafenib Treatment ◽  
Baseline Activity ◽  
Dose Dependent

The multikinase inhibitor sorafenib is the only standard first-line therapy for hepatocellular carcinoma (HCC). Here, we report the dose-dependent effects of sorafenib on the immune response, which is related to nuclear factor of activated T cells 1 (NFAT1) activity. In vitro and in vivo experiments were performed with low and high doses of sorafenib using human T cells and spontaneous developed woodchuck HCC models. In vitro studies demonstrated that following exposure to a high dose of sorafenib the baseline activity of NFAT1 in T cells was significantly increased. In a parallel event, high dose sorafenib resulted in a significant decrease in T cell proliferation and increased the proportion of PD-1 expressing CD8+ T cells with NFAT1 activation. In the in vivo model, smaller tumors were detected in the low-dose sorafenib treated group compared to the placebo and high-dose treated groups. The low-dose sorafenib group showed a significant tumor growth delay with significantly more CD3+ cells in tumor. This study demonstrates that sorafenib has immunomodulatory effects in a dose- and time-dependent manner. Higher dose of sorafenib treatment was associated with immunosuppressive action. This observed effect of sorafenib should be taken into consideration in the selection of optimum starting dose for future trials.

scholarly journals Studies on Agranulocytosis. IV. Effects of Chlorpromazine on Nucleic Acid Synthesis of Bone Marrow Cells in Vitro

Blood ◽  
1962 ◽  
Vol 20 (3) ◽  
pp. 364-376 ◽  
Author(s):  
ANTHONY V. PISCIOTTA ◽  
JOYCE KALDAHL
Keyword(s):  
Nucleic Acid ◽  
Bone Marrow Cells ◽  
Leukocyte Count ◽  
Tritiated Thymidine ◽  
Acid Synthesis ◽  
Nucleic Acid Synthesis ◽  
Hospital Patients ◽  
Dose Dependent ◽  
Marrow Cells

Abstract 1. When viable marrow cells were incubated with tritiated thymidine and uridine, the cells became radioactive as nucleic acid synthesis proceeded. 2. Excessive concentrations of chlorpromazine (CPZ) partially inhibited the influx of thymidine and uridine into granulocytes of all patients who had had agranulocytosis due to this drug, and of about 75 per cent of random hospital patients. This drug did not effect nucleic acid synthesis in nine individuals who had been treated with a large amount of CPZ, with no alteration in their leukocyte count. 3. A comparison of the effects of dilution of CPZ upon influx of H3 thymidine into granulocytes showed significant dose-dependent depression of granulocyte labeling in CPZ sensitive persons, and no depression in granulocytes of persons on large doses of CPZ who did not develop leukopenia. Random hospital patients not on CPZ showed a degree of depression between these two groups. 4. The number of radioactive normoblasts in the marrow culture preparations diminished slightly, but not significantly, following incubation with CPZ. 5. Non-myelotoxic drugs, such as Phenergan, aspirin, penicillin, and tetracyclene had no significant effect on the degree of influx of tritated thymidine and uridine. 6. There was no effect of CPZ upon incorporation of H3 DL-leucine into marrow cells.

scholarly journals In VitroToxicity Evaluation of Engineered Cadmium-Coated Silica Nanoparticles on Human Pulmonary Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Uliana De Simone ◽  
Luigi Manzo ◽  
Antonella Profumo ◽  
Teresa Coccini
Keyword(s):  
Silica Nanoparticles ◽  
Low Dose ◽  
Membrane Integrity ◽  
Apoptotic Pathway ◽  
Cytotoxic Effects ◽  
Pulmonary Cells ◽  
Calcein Am ◽  
Dose Dependent

Cytotoxicity of cadmium-containing silica nanoparticles Cd-SiO2NPs (0.05–100 µg/mL) versus SiO2NPs and CdCl2was evaluated by anin vitrotest battery in A549 by assessing (i) mitochondrial function, (ii) membrane integrity/cell morphology, (iii) cell growth/proliferation, (iv) apoptotic pathway, (v) oxidative stress, after short- (24–48 h) and long-term (10 days) exposure. Both Cd-SiO2NPs and CdCl2produced dose-dependent cytotoxic effects: (i)MTT-assay: similar cytotoxicity pattern was observed at both 24 and 48 h, with a more Cd-SiO2NPs pronounced effect than CdCl2. Cd-SiO2NPs induced mortality (about 50%) at 1 μg/mL, CdCl2at 25 μg/mL; (ii)calcein-AM/PI staining: decrease in cell viability, noticeable at 25 μg/mL, enhanced markedly at 50 and 100 μg/mL, after 24 h. Cd-SiO2NPs induced higher mortality than CdCl2(25% versus 4%, resp., at 25 μg/mL) with further exacerbation after 48h; (iii)clonogenic assay: exposure for longer period (10 days) compromised the A549 proliferative capacity at very low dose (0.05 μg/mL); (iv) a progressive activation ofcaspase-3 immunolabellingwas detected already at 1 μg/mL; (v) GSH intracellular level was modified by all compounds. In summary,in vitrodata demonstrated that both Cd-SiO2NPs and CdCl2affected all investigated endpoints, more markedly after Cd-SiO2NPs, while SiO2NPs influenced GSH only.

Increased Protein Synthesis by Human Platelets during Phagocytosis of Latex Particles in Vitro

1976 ◽  
Vol 35 (02) ◽  
pp. 350-357 ◽  
Author(s):  
Hana Bessler ◽  
Galila Agam ◽  
Meir Djaldetti
Keyword(s):  
Protein Synthesis ◽  
Fold Increase ◽  
Human Platelets ◽  
Polystyrene Latex ◽  
Latex Particles ◽  
The Third ◽  
Platelet Protein ◽  
Dose Dependent ◽  
Phagocytotic Activity

SummaryA three-fold increase of protein synthesis by human platelets during in vitro phagocytosis of polystyrene latex particles was detected. During the first two hours of incubation, the percentage of phagocytizing platelets and the number of latex particles per platelet increased; by the end of the third hour, the first parameter remained stable, while the number of latex particles per cell had decreased.Vincristine (20 μg/ml of cell suspension) inhibited platelet protein synthesis. This effect was both time- and dose-dependent. The drug also caused a decrease in the number of phagocytizing cells, as well as in their phagocytotic activity.

The Effect of Adrenaline Infusions on Blood Coagulation in Normal and Haemophilia B Dogs

1966 ◽  
Vol 15 (03/04) ◽  
pp. 349-364 ◽  
Author(s):  
A.H Özge ◽  
H.C Rowsell ◽  
H.G Downie ◽  
J.F Mustard
Keyword(s):  
Body Weight ◽  
Factor Viii ◽  
Factor Ix ◽  
Clotting Factor ◽  
Blood Ph ◽  
Order Of Magnitude ◽  
Dose Dependent ◽  
Generation Test ◽  
Plasma Activity

SummaryThe addition of trace amounts of adrenaline to whole blood in plasma in vitro increased factor VIII, factor IX and whole plasma activity in the thromboplastin generation test. This was dose dependent.Adrenaline infusions less than 22 (μg/kg body weight in normal dogs accelerated clotting, increased factor IX, factor VIII and whole plasma activity in the thromboplastin generation test and caused a fall in blood pH. In a factor IX deficient dog, there was no increase in factor IX activity. After adrenaline infusions, however, the other changes occurred and were of the same order of magnitude as in the normal. Adrenaline in doses greater than 22 μg/kg body weight did not produce as great an effect on clotting in normal or factor IX deficient dogs. The platelet count in the peripheral blood was increased following the infusion of all doses of adrenaline. These observations suggest that the accelerating effect of adrenaline on clotting is not mediated through increase in activity of a specific clotting factor.

Soluble Thrombomodulin Purified from Human Urine Exhibits a Potent Anticoagulant Effect In Vitro and In Vivo

1995 ◽  
Vol 73 (05) ◽  
pp. 805-811 ◽  
Author(s):  
Yasuo Takahashi ◽  
Yoshitaka Hosaka ◽  
Hiromi Niina ◽  
Katsuaki Nagasawa ◽  
Masaaki Naotsuka ◽  
...  
Keyword(s):  
Human Urine ◽  
Specific Activity ◽  
Anticoagulant Activity ◽  
Rabbit Lung ◽  
Soluble Thrombomodulin ◽  
Molecular Weights ◽  
Dose Dependent Fashion ◽  
Dose Dependent

SummaryWe examined the anticoagulant activity of two major molecules of soluble thrombomodulin purified from human urine. The apparent molecular weights of these urinary thrombomodulins (UTMs) were 72,000 and 79,000, respectively. Both UTMs showed more potent cofactor activity for protein C activation [specific activity >5,000 thrombomodulin units (TMU)/mg] than human placental thrombomodulin (2,180 TMU/mg) and rabbit lung thrombomodulin (1,980 TMU/mg). The UTMs prolonged thrombin-induced fibrinogen clotting time (>1 TMU/ml), APTT (>5 TMU/ml), TT (>5 TMU/ml) and PT (>40 TMU/ml) in a dose-dependent fashion. These effects appeared in the concentration range of soluble thrombomodulins present in human plasma and urine. In the rat DIC model induced by thromboplastin, administration of UTMs by infusion (300-3,000 TMU/kg) restored the hematological abnormalities derived from DIC in a dose-dependent fashion. These results demonstrate that UTMs exhibit potent anticoagulant and antithrombotic activities, and could play a physiologically important role in microcirculation.

Oxygenation of 18-hydroxycorticosterone as the final reaction for aldosterone biosynthesis

1984 ◽  
Vol 107 (3) ◽  
pp. 395-400 ◽  
Author(s):  
Itaru Kojima ◽  
Etsuro Ogata ◽  
Hiroshi Inano ◽  
Bun-ichi Tamaoki
Keyword(s):  
Carbon Monoxide ◽  
Hydroxysteroid Dehydrogenase ◽  
Dependent Manner ◽  
In Vitro Production ◽  
Mitochondrial Preparation ◽  
Final Reaction ◽  
Vitro Production ◽  
Dose Dependent ◽  
Cytochrome P 450

Abstract. Incubation of 18-hydroxycorticosterone with the sonicated mitochondrial preparation of bovine adrenal glomerulosa tissue leads to the production of aldosterone, as measured by radioimmunoassay. The in vitro production of aldosterone from 18-hydroxycorticosterone requires both molecular oxygen and NADPH, and is inhibited by carbon monoxide. Cytochrome P-450 inhibitors such as metyrapone, SU 8000. SU 10603, SKF 525A, amphenone B and spironolactone decrease the biosynthesis of aldosterone from 18-hydroxycorticosterone. These results support the conclusion that the final reaction in aldosterone synthesis from 18-hydroxycorticosterone is catalyzed by an oxygenase, but not by 18-hydroxysteroid dehydrogenase. By the same preparation, the production of [3H]aldosterone but not [3H]18-hydroxycorticosterone from [1,2-3H ]corticosterone is decreased in a dose-dependent manner by addition of non-radioactive 18-hydroxycorticosterone.

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