STUDIES ON ECTOPIC ACTH-PRODUCING TUMOURS.

1976 ◽  
Vol 82 (1) ◽  
pp. 183-192 ◽  
Author(s):  
H. Yamamoto ◽  
Y. Hirata ◽  
S. Matsukura ◽  
H. Imura ◽  
M. Nakamura ◽  
...  
Keyword(s):  
Dose Response ◽  
Arginine Vasopressin ◽  
Response Curve ◽  
Assay Method ◽  
Ectopic Acth ◽  
Ectopic Production ◽  
Releasing Factors ◽  
Incubation Method ◽  
Tumour Extract

ABSTRACT In order to elucidate whether ectopic ACTH-producing tumours elaborate corticotrophin-releasing factors (CRF)-like materials, the CRF-like activity of tumour extracts was measured by the in vitro pituitary incubation method. Seven out of 12 tumour extracts with suspected ACTH-producing tumours showed CRF-like activity. No correlation was found between ACTH and CRF-like activities in tumour extracts in which both activities were present. The dose-response curve of a tumour extract was almost parallel to that of crude CRF (NIAMDD) and clearly different from those of lysine-8-vasopressin and arginine-vasopressin, both of which showed CRF-like activity by this assay method. Trypsin digestion considerably lowered the CRF-like activity of a tumour extract. These results suggest that ectopic production of CRF-like substance(s) occurs more frequently than was supposed previously, especially in ACTH-producing tumours.

ETUDE DE L'ACTION DU FACTEUR HYPOTHALAMIQUE LRF (LH-RELEASING FACTOR) CHEZ LE RAT IN VIVO & IN VITRO

1967 ◽  
Vol 55 (3) ◽  
pp. 481-496 ◽  
Author(s):  
Marian Jutisz ◽  
Annette Bérault ◽  
Marie-Anne Novella ◽  
Geneviève Ribot
Keyword(s):  
Dose Response ◽  
Crude Extract ◽  
Response Curve ◽  
Assay Method ◽  
Hypothalamic Extract ◽  
Rat Pituitary ◽  
Pituitary Glands ◽  
Releasing Effect

ABSTRACT A highly purified ovine LH-releasing factor (LRF) was obtained by a modification of the method previously described. After the fractionation of a crude hypothalamic extract on a Sephadex G-25 column, the LRF fraction was desalted and partially purified by chromatography on a Dowex 50 × 12 column and on an Amberlite CG 4B column. The last step of this method, chromatography on a CMC column, gave a purification of about 1600 times with respect to the crude extract. The action of this highly purified LRF preparation was studied on rat pituitary glands in vivo and in vitro. The method used in vivo was the evaluation of the LH-releasing effect of LRF in chronically ovariectomized, steroid-blocked rats (Ramirez & McCann 1963 b). A procedure was developed which allows a 4-fold concentration of the plasma LH from these rats, so that it can be assayed by a 4-point assay method. In the in vitro method, the pituitary glands of ovariectomized steroidblocked rats (Schally & Bowers 1964 a) were incubated in a Krebs-Ringer buffer with or without LRF, and the LH released into the medium was assayed using the O.A. A.D. method of Parlow. A dose-response curve was established between the log doses of LRF and the amount of LH released. This method can be used as a sensitive and specific assay for LRF. It was shown that a dose of 1.22 μg of LRF releases approximately 5 μg of LH per mg of pituitary tissue. This is about double of the amount of this hormone originally present in the pituitary glands of these rats (2.7 μg/mg). This leads us to the conclusion that the excess of this hormone was probably synthetized during the process of incubation. The amount of steroids injected as a blocking agents, appears to be very important for both in vivo and in vitro tests.

scholarly journals Predicting the in vivo developmental toxicity of benzo[a]pyrene (BaP) in rats by an in vitro–in silico approach

2021 ◽  
Author(s):  
Danlei Wang ◽  
Maartje H. Rietdijk ◽  
Lenny Kamelia ◽  
Peter J. Boogaard ◽  
Ivonne M. C. M. Rietjens
Keyword(s):  
Dose Response ◽  
In Silico ◽  
Response Curve ◽  
Developmental Toxicity ◽  
Toxicity Testing ◽  
Maximal Effect ◽  
Blood Concentrations ◽  
Reverse Dosimetry

AbstractDevelopmental toxicity testing is an animal-intensive endpoints in toxicity testing and calls for animal-free alternatives. Previous studies showed the applicability of an in vitro–in silico approach for predicting developmental toxicity of a range of compounds, based on data from the mouse embryonic stem cell test (EST) combined with physiologically based kinetic (PBK) modelling facilitated reverse dosimetry. In the current study, the use of this approach for predicting developmental toxicity of polycyclic aromatic hydrocarbons (PAHs) was evaluated, using benzo[a]pyrene (BaP) as a model compound. A rat PBK model of BaP was developed to simulate the kinetics of its main metabolite 3-hydroxybenzo[a]pyrene (3-OHBaP), shown previously to be responsible for the developmental toxicity of BaP. Comparison to in vivo kinetic data showed that the model adequately predicted BaP and 3-OHBaP blood concentrations in the rat. Using this PBK model and reverse dosimetry, a concentration–response curve for 3-OHBaP obtained in the EST was translated into an in vivo dose–response curve for developmental toxicity of BaP in rats upon single or repeated dose exposure. The predicted half maximal effect doses (ED50) amounted to 67 and 45 mg/kg bw being comparable to the ED50 derived from the in vivo dose–response data reported for BaP in the literature, of 29 mg/kg bw. The present study provides a proof of principle of applying this in vitro–in silico approach for evaluating developmental toxicity of BaP and may provide a promising strategy for predicting the developmental toxicity of related PAHs, without the need for extensive animal testing.

EFFECT OF VARIOUS PREPARATIONS OF PITUITARY AND DIENCEPHALON ON THE IN VITRO SECRETION OF ALDOSTERONE AND CORTICOSTERONE BY THE RAT ADRENAL GLAND

1961 ◽  
Vol 39 (5) ◽  
pp. 901-913 ◽  
Author(s):  
O. J. Lucis ◽  
I. Dyrenfurth ◽  
E. H. Venning
Keyword(s):  
Adrenal Gland ◽  
Linear Relationship ◽  
Dose Response ◽  
Response Curve ◽  
Maximum Effect ◽  
Percentage Increase ◽  
Aldosterone Secretion ◽  
Maximal Stimulation ◽  
Stimulation Of

Purified corticotropin and ACTH peptides increased the secretion of aldosterone, corticosterone, and an unidentified compound RT4in incubated rat adrenal tissue. When the response was expressed as a percentage increase above that of the control tissue, the increases in corticosterone and compound RT4followed a sigmoid log dose – response curve. The maximum effect on aldosterone was obtained at a time when the response curve for corticosterone assumed a linear relationship between the response and the logarithm of the dose of ACTH. This dose level was considerably less than that required for maximal stimulation of corticosterone.The capacity of the ACTH peptides α1+α2and δ′ for stimulating aldosterone secretion could be greatly diminished by allowing solutions of these fractions to stand at 5 °C for 1 week. These solutions still retained their ability to stimulate corticosterone secretion.Saline suspensions and extracts of fresh hog diencephalon contained a factor which selectively stimulated aldosterone secretion.

Mechanisms of histamine-induced contraction of canine airway smooth muscle

1983 ◽  
Vol 55 (1) ◽  
pp. 22-26 ◽  
Author(s):  
S. Shore ◽  
C. G. Irvin ◽  
T. Shenkier ◽  
J. G. Martin
Keyword(s):  
Smooth Muscle ◽  
Dose Response ◽  
Response Curve ◽  
Line Tension ◽  
Isometric Tension ◽  
Dose Response Curve ◽  
Base Line ◽  
Histamine Concentration ◽  
Release Of Acetylcholine

We studied the effects of atropine (10(-10) to 10(-6) M), tetrodotoxin (TTX) (10(-6) g/ml), and neostigmine (10(-7) M) on the histamine dose-response curve of canine tracheal smooth muscle (TSM) in vitro. Pretreatment with atropine or TTX reduced base-line tension in some TSM samples, whereas neostigmine invariably caused contraction of TSM. All concentrations of atropine reduced the maximum isometric tension produced by histamine (Tmax). With 10(-6), 10(-8), and 10(-10) M atropine, Tmax was 57, 74, and 88%, respectively, of its value in paired control samples. Atropine, 10(-9) to 10(-6) M, increased the concentration of histamine which produced 20% of Tmax, whereas 10(-6) M also increased the concentration required to produce 50% of Tmax. TTX reduced tension produced by low concentrations of histamine but had no effect at higher concentrations. Neostigmine shifted the histamine dose-response curve and caused greater tension for any given histamine concentration; Tmax increased by 30% (P less than 0.05). Our data are consistent with spontaneous release of acetylcholine from cholinergic nerves in the airway tissue and suggest that histamine either accelerates this release or interacts supra-additively with the acetylcholine at the smooth muscle.

AN IN VITRO ASSAY OF CORTICOTROPHIN

1955 ◽  
Vol 33 (2) ◽  
pp. 209-216 ◽  
Author(s):  
K. W. McKerns ◽  
E. Nordstrand
Keyword(s):  
Dose Response ◽  
In Vitro Assay ◽  
Assay Method ◽  
Response Curves ◽  
Vitro Assay ◽  
Rat Adrenals ◽  
Assay Design ◽  
Dose Response Curves ◽  
Gland System

The ability of corticotrophin to increase the corticoid output of rat adrenals in an isolated gland system has been developed as a useful assay method for the measurement of corticotrophin potency. The extra corticoids produced by stimulation are measured in terms of cortisone. Log dose response curves are presented for corticotrophin levels from 0.002 to 0.135 I.U./100 mgm. adrenals. A four point assay design, the precision of corticoid measurements, and the characteristics of the log dose response curves for a number of types of corticotrophin are given. With four measurements of each dose level the average lambda s/b for 20 assays was 0.209 ± 0.085 (S.D.).

Alterations in the functional properties of skinned fibers from denervated rabbit skeletal muscle

1990 ◽  
Vol 259 (3) ◽  
pp. C503-C506 ◽  
Author(s):  
M. M. Trachez ◽  
R. T. Sudo ◽  
G. Suarez-Kurtz
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Functional Properties ◽  
Dose Response ◽  
Response Curve ◽  
Extensor Digitorum Longus ◽  
Isometric Tension ◽  
Skinned Fibers ◽  
Spontaneous Release

Isometric tension was recorded in vitro from chemically skinned fibers obtained from normal and 14-day-denervated extensor digitorum longus muscles of the rabbit. Denervation potentiated the tensions elicited by pCa 6.0 but did not modify the pCa value (5.6) required for maximum tension. Ca2+ transport across the membranes of the sarcoplasmic reticulum (SR) was markedly affected by denervation. Thus the rate of ATP-dependent net Ca2+ uptake increased significantly, and the spontaneous release ("leakage") of the Ca2+ stored in the SR was significantly reduced in denervated fibers. These effects lead to increased accumulation of Ca2+ in the lumen of the SR. The dose-response curve for the halothane-induced contractures of Ca2(+)-loaded skinned fibers was displaced to the left after denervation. Thus 0.7 mM halothane, a concentration that elicited no tension in 10 control fibers, induced contractures in the 10 denervated fibers tested. The potentiation of the halothane-induced tensions is attributed mainly to the larger stores of Ca2+ in the SR of denervated fibers. The possibility that denervation may also affect the interaction of halothane with the SR membranes is discussed.

scholarly journals Cd2 Sets Quantitative Thresholds in T Cell Activation

1999 ◽  
Vol 190 (10) ◽  
pp. 1383-1392 ◽  
Author(s):  
Martin F. Bachmann ◽  
Marijke Barner ◽  
Manfred Kopf
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Dose Response ◽  
Response Curve ◽  
Cell Activation ◽  
Dose Response Curve ◽  
Lymphocyte Function

It has been proposed that CD2, which is highly expressed on T cells, serves to enhance T cell–antigen presenting cell (APC) adhesion and costimulate T cell activation. Here we analyzed the role of CD2 using CD2-deficient mice crossed with transgenic mice expressing a T cell receptor specific for lymphocytic choriomeningitis virus (LCMV)-derived peptide p33. We found that absence of CD2 on T cells shifted the p33-specific dose–response curve in vitro by a factor of 3–10. In comparison, stimulation of T cells in the absence of lymphocyte function–associated antigen (LFA)-1–intercellular adhesion molecule (ICAM)-1 interaction shifted the dose–response curve by a factor of 10, whereas absence of both CD2–CD48 and LFA-1–ICAM-1 interactions shifted the response by a factor of ∼100. This indicates that CD2 and LFA-1 facilitate T cell activation additively. T cell activation at low antigen density was blocked at its very first steps, as T cell APC conjugate formation, TCR triggering, and Ca2+ fluxes were affected by the absence of CD2. In vivo, LCMV-specific, CD2-deficient T cells proliferated normally upon infection with live virus but responded in a reduced fashion upon cross-priming. Thus, CD2 sets quantitative thresholds and fine-tunes T cell activation both in vitro and in vivo.

AN IN VITRO ASSAY OF CORTICOTROPHIN

1955 ◽  
Vol 33 (1) ◽  
pp. 209-216
Author(s):  
K. W. McKerns ◽  
E. Nordstrand
Keyword(s):  
Dose Response ◽  
In Vitro Assay ◽  
Assay Method ◽  
Response Curves ◽  
Vitro Assay ◽  
Rat Adrenals ◽  
Assay Design ◽  
Dose Response Curves ◽  
Gland System

The ability of corticotrophin to increase the corticoid output of rat adrenals in an isolated gland system has been developed as a useful assay method for the measurement of corticotrophin potency. The extra corticoids produced by stimulation are measured in terms of cortisone. Log dose response curves are presented for corticotrophin levels from 0.002 to 0.135 I.U./100 mgm. adrenals. A four point assay design, the precision of corticoid measurements, and the characteristics of the log dose response curves for a number of types of corticotrophin are given. With four measurements of each dose level the average lambda s/b for 20 assays was 0.209 ± 0.085 (S.D.).

Comparison of Activated Partial Thromboplastin Time Ratios with Ecarin Clotting Time Ratios for Monitoring Direct Thrombin Inhibitor Therapy: In-Vitro Study and Case Study of Lepirudin Therapy.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4149-4149
Author(s):  
Harry L. Messmore ◽  
Nancy J. Fabbrini ◽  
Ketty Badrinath ◽  
Richard Harriman ◽  
Omar Iqbal ◽  
...  
Keyword(s):  
Dose Response ◽  
Partial Thromboplastin Time ◽  
Response Curve ◽  
Activated Partial Thromboplastin Time ◽  
Dose Response Curve ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Blood Levels ◽  
Clotting Time

Abstract The direct thrombin inhibitors lepirudin and argatroban are widely used to treat heparin induced thrombocytopenia (HIT). It has been suggested that the Ecarin™ (Echis carinatus venom) clotting time may be superior to the activated partial thromboplastin time (APTT) for monioring purposes. We have prepared standard curves for lepirudin (Refludan™) and Argatroban covering therapeutic drug levels and corresponding APTT ratios (clotting time/control clotting time). Ecarin™ clotting time ratios were performed to demonstrate the practical application of these curves in the clinical care of patients. We report the case of an 80 year old man with HIT/HITT syndrome that occurred during therapy for deep vein thrombosis (DVT) with a low molecular weight heparin (LMWH). His initial coagulation studies were abnormal due to warfarin and LMWH therapy. The patient had a moderate impairment of renal function. Lepirudin therapy in a bolus dose of 14 mg (patient weight: 103.0 kg) resulted in supratherapeutic blood levels of drug and hematuria (Platelet count: 〉200 x 103). Dosage adjustment to maintain an APTT ratio of 1.5 for five days caused no hematuria, but thromboembolic complications occurred at that ratio. The in-vitro dose response curve for Lepirudin was compared with the Ecarin™ clotting time (ECT) ratio at those same concentration ranges in the same plasma. For comparison, Argatroban dose response curves in-vitro were made as well. ECT ratios were very similar to the APTT ratios in the patient’s samples. Representative ratios after the initial bolus, during the infusion period of five days and at the termination of that period are shown in the following table: Comparison of APTT and ECT Ratios APTT Ratio ECT Ratio 1.43 1.07 3.98 3.08 2.91 1.95 2.74 1.95 2.79 1.90 2.58 1.78 2.44 2.42 3.83 4.78 Conclusion: The ECT ratios reflect a steeper dose response curve than that observed with the APTT ratios. This may permit more accurate measurement of blood levels using ECT ratios.

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