scholarly journals The Influence of Human Interindividual Variability on the Low-Dose Region of Dose-Response Curve Induced by 2,3,7,8-Tetrachlorodibenzo-p-Dioxin in Primary B Cells

2016 ◽  
Vol 153 (2) ◽  
pp. 352-360 ◽  
Author(s):  
Peter Dornbos ◽  
Robert B. Crawford ◽  
Norbert E. Kaminski ◽  
Sarah L. Hession ◽  
John J. LaPres
Keyword(s):  
B Cells ◽  
Dose Response ◽  
Response Curve ◽  
Low Dose ◽  
Interindividual Variability ◽  
Dose Response Curve ◽  
Tetrachlorodibenzo P Dioxin

scholarly journals Mitogen-induced phosphorylation of human B-lymphocyte proteins. Relationship to protein kinase C activation

1989 ◽  
Vol 263 (1) ◽  
pp. 57-64 ◽  
Author(s):  
G R Guy ◽  
M Finney ◽  
R H Michell ◽  
J Gordon
Keyword(s):  
Protein Kinase C ◽  
B Cells ◽  
Protein Kinase ◽  
B Lymphocytes ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Beta Form ◽  
Kinase C ◽  
Hydrolysis Of

We have investigated the rapid phosphorylation of proteins in B-lymphocytes incubated with the tumour-promoting phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), anti-Ig and combinations of TPA and the Ca2+ ionophore ionomycin. Two-dimensional electrophoretic analysis was used to identify the proteins phosphorylated in cells preincubated with [32P]Pi. TPA induced a characteristic pattern of labelled proteins, four of which (pp85, pp76, pp66 and pp63) showed a dose-dependent incorporation of 32P on serine residues. The phosphorylation of pp63 and pp66, in particular, correlated with the mitogenic dose-response curve. Addition of the Ca2+ ionophore ionomycin to B-cells also stimulated a characteristic incorporation of 32P into proteins, which included pp63 and pp66. With combined doses of TPA and ionomycin, these two proteins show an enhanced phosphorylation, which correlated well with the synergistic enhancement of proliferation shown by this combination of agents. Protein kinase C (PKC) was partially purified from B-cells and separated into alpha and beta subtypes. The activation of both PKCs was assessed with increasing doses of TPA and concentrations of Ca2+ of 0.1 microM and 2 microM. For both forms of PKC, in particular the beta form, higher concentrations of Ca2+ shifted the dose-response curve for TPA to the left and increased the maximum activation. Anti-Ig, which stimulated B-cells by cross-linking surface immunoglobulin and causing hydrolysis of PtdIns(4,5)P2, also caused increased phosphorylation of several proteins, which again included pp63 and pp66. These data suggest that PKC, particularly the beta form, is involved in the early part of the proliferation cascade for human B-lymphocytes. It is most probably activated in a synergistic manner by the increased Ca2+ and diacylglycerol levels which result from the earlier hydrolysis of PtdIns(4,5)P2.

Relevance of Non-Targeted Effects for Radiotherapy and Diagnostic Radiology

2019 ◽  
Author(s):  
Carmel Mothersill ◽  
Andrej Rusin ◽  
Colin Seymour
Keyword(s):  
Nuclear Medicine ◽  
Genomic Instability ◽  
Dose Response ◽  
Response Curve ◽  
Low Dose ◽  
Dose Response Curve ◽  
Diagnostic Radiology ◽  
Second Cancer ◽  
Cancer Induction ◽  
Medical Diagnostic

Non-targeted effects (NTE) such as bystander effects or genomic instability have been known for many years but their significance for radiotherapy or medical diagnostic radiology are far from clear. Central to the issue are reported differences in response of normal and tumour tissues to signals from directly irradiated cells. This review will discuss possible mechanisms and implications of these different responses and will then discuss possible new therapeutic avenues suggested by the analysis. Finally, the importance of NTE for diagnostic radiology and nuclear medicine which stems from the dominance of NTE in the low dose region of the dose response curve will be presented. Areas such as second cancer induction and microenvironment plasticity will be discussed.

scholarly journals Effect of adding oat bran to instant oatmeal on glycaemic response in humans – a study to establish the minimum effective dose of oat β-glucan

2018 ◽  
Vol 9 (3) ◽  
pp. 1692-1700 ◽  
Author(s):  
Thomas M. S. Wolever ◽  
Alexandra L. Jenkins ◽  
Kevin Prudence ◽  
Jodee Johnson ◽  
Ruedi Duss ◽  
...  
Keyword(s):  
Effective Dose ◽  
Dose Response ◽  
Response Curve ◽  
Low Dose ◽  
Dose Response Curve ◽  
Minimum Effective Dose ◽  
Glycaemic Response ◽  
Oat Bran ◽  
High Doses

The slope of the present dose–response curve for low-dose oat β-glucan (g/g available-carbohydrate) is equivalent to that for high doses.

scholarly journals STUDIES ON THE INDUCTION OF IMMUNOLOGICAL UNRESPONSIVENESS TO PNEUMOCOCCAL POLYSACCHARIDE IN MICE

1966 ◽  
Vol 124 (3) ◽  
pp. 417-429 ◽  
Author(s):  
Gregory W. Siskind ◽  
James G. Howard
Keyword(s):  
Immune Response ◽  
Dose Response ◽  
Response Curve ◽  
Low Dose ◽  
Dose Response Curve ◽  
Transient Phase ◽  
Protein Antigens ◽  
Response Curves ◽  
Corynebacterium Parvum ◽  
Competent Cells

1. Comparison of dose-response curves indicated that preimmunized animals were slightly more susceptible to the induction of immunological paralysis with pneumococcal polysaccharide than were normal mice. The results also indicated that the paralysis threshold was unaltered by preimmunization. 2. Transient desensitization of immunized mice could be achieved by an amount of polysaccharide far less than that required to induce paralysis. 3. A transient phase of weak immunity was detected prior to the onset of paralysis when induced by relatively low paralyzing doses of polysaccharide. 4. No "low dose" zone of paralysis (analogous to that obtainable with certain protein antigens) could be elicited with pneumococcal polysaccharide. 5. Massive proliferation of lymphoreticular tissues induced by Corynebacterium parvum failed to raise the threshold for paralysis induction, but amplified the immune response over the entire dose-response curve. Similarly, C. parvum failed to abrogate an established state of paralysis. The results suggest that the induction of polysaccharide paralysis is related to the concentration of antigen in the animal and is not modified by the number of immunologically competent cells.

Insulin secretion and clearance during low-dose graded glucose infusion

1995 ◽  
Vol 268 (1) ◽  
pp. E21-E27 ◽  
Author(s):  
M. M. Byrne ◽  
J. Sturis ◽  
K. S. Polonsky
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Dose Response ◽  
Response Curve ◽  
Low Dose ◽  
Compartment Model ◽  
Glucose Infusion ◽  
Dose Response Curve ◽  
Intravenous Glucose ◽  
Normal Volunteers

The present study was undertaken in normal volunteers to define the alterations in beta-cell responsiveness to glucose associated with different physiological states, including fasting and refeeding, and after prolonged intravenous glucose infusion. A low-dose graded glucose infusion protocol was used to explore the dose-response relationship between glucose and insulin secretion. Studies were performed in 10 normal volunteers, and insulin secretion rates (ISR) were calculated by deconvolution of peripheral C-peptide levels using a two-compartment model utilizing individual kinetic parameters. From 5 to 9 mmol/l glucose, the relationship between glucose and ISR was linear. After a 42-h glucose infusion at a rate of 4 mg.kg-1.min-1, the ISR increased by 53% over the same glucose concentration range (P < 0.002), resulting in a shift of the dose-response curve to the left. Insulin clearance rates decreased 27% after the 42-h glucose infusion (P < 0.001). After a 72-h fast, ISR decreased by 32% from baseline over the 5-8 mmol/l glucose range (P = 0.056), resulting in a shift of the dose-response curve to the right. This shift was reversed by a 42-h period of refeeding, after which ISR was increased by 77% compared with the fasting study (P < 0.02). Refeeding enhanced the beta-cell responsiveness, and ISR increased by 31% after refeeding compared with the baseline study (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-Response Curve for Chromosome Translocations Induced by Low Dose Rate 137Cs Gamma Rays

1997 ◽  
Vol 71 (4) ◽  
pp. 279-282 ◽  
Author(s):  
J.N. Lucas ◽  
F.S. Hill ◽  
C.E. Burk ◽  
A.D. Lewis ◽  
A.K. Lucas ◽  
...  
Keyword(s):  
Dose Rate ◽  
Gamma Rays ◽  
Dose Response ◽  
Response Curve ◽  
Low Dose ◽  
Dose Response Curve ◽  
Chromosome Translocations ◽  
Low Dose Rate

OVARIAN ASCORBIC ACID DEPLETION TEST FOR LUTEINIZING HORMONE

1967 ◽  
Vol 56 (4) ◽  
pp. 619-625 ◽  
Author(s):  
Hans Jacob Koed ◽  
Christian Hamburger
Keyword(s):  
Ascorbic Acid ◽  
Luteinizing Hormone ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Human Origin ◽  
Response Curves ◽  
Significant Difference ◽  
The Mean ◽  
Different Levels

ABSTRACT Comparison of the dose-response curves for LH of ovine origin (NIH-LH-S8) and of human origin (IRP-HMG-2) using the OAAD test showed a small, though statistically significant difference, the dose-response curve for LH of human origin being a little flatter. Two standard curves for ovine LH obtained with 14 months' interval, were parallel but at different levels of ovarian ascorbic acid. When the mean ascorbic acid depletions were calculated as percentages of the control levels, the two curves for NIH-LH-S8 were identical. The use of standards of human origin in the OAAD test for LH activity of human preparations is recommended.

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