scholarly journals High specific activity tritium-labeled N-(2-methoxybenzyl)-2,5-dimethoxy-4-iodophenethylamine (INBMeO): A high-affinity 5-HT2A receptor-selective agonist radioligand

2008 ◽  
Vol 16 (11) ◽  
pp. 6116-6123 ◽  
Author(s):  
David E. Nichols ◽  
Stewart P. Frescas ◽  
Benjamin R. Chemel ◽  
Kenneth S. Rehder ◽  
Desong Zhong ◽  
...  
Keyword(s):  
Specific Activity ◽  
High Specific Activity ◽  
High Affinity ◽  
Selective Agonist

Effects of Heparin Oligosaccharides with High Affinity for Antithrombin III in Experimental Venous Thrombosis

1982 ◽  
Vol 47 (03) ◽  
pp. 244-248 ◽  
Author(s):  
D P Thomas ◽  
Rosemary E Merton ◽  
T W Barrowcliffe ◽  
L Thunberg ◽  
U Lindahl
Keyword(s):  
Antithrombin Iii ◽  
Specific Activity ◽  
High Specific Activity ◽  
Factor Xa ◽  
Blood Levels ◽  
Thrombin Time ◽  
High Affinity ◽  
Very High

SummaryThe in vitro and in vivo characteristics of two oligosaccharide heparin fragments have been compared to those of unfractionated mucosal heparin. A decasaccharide fragment had essentially no activity by APTT or calcium thrombin time assays in vitro, but possessed very high specific activity by anti-Factor Xa assays. When injected into rabbits at doses of up to 80 ¼g/kg, this fragment was relatively ineffective in impairing stasis thrombosis despite producing high blood levels by anti-Xa assays. A 16-18 monosaccharide fragment had even higher specific activity (almost 2000 iu/mg) by chromogenic substrate anti-Xa assay, with minimal activity by APTT. When injected in vivo, this fragment gave low blood levels by APTT, very high anti-Xa levels, and was more effective in preventing thrombosis than the decasaccharide fragment. However, in comparison with unfractionated heparin, the 16-18 monosaccharide fragment was only partially effective in preventing thrombosis, despite producing much higher blood levels by anti-Xa assays.It is concluded that the high-affinity binding of a heparin fragment to antithrombin III does not by itself impair venous thrombogenesis, and that the anti-Factor Xa activity of heparin is only a partial expression of its therapeutic potential.

Measuring thyroxine and thyrotropin simultaneously in a dried blood sample on filter paper, to screen for neonatal hypothyroidism.

1980 ◽  
Vol 26 (6) ◽  
pp. 750-753
Author(s):  
S Nagataki ◽  
K Ishibashi ◽  
R Ohsawa ◽  
S Suwa ◽  
N Tsukamoto ◽  
...  
Keyword(s):  
Filter Paper ◽  
Specific Activity ◽  
High Specific Activity ◽  
High Sensitivity ◽  
Recall Rate ◽  
Neonatal Hypothyroidism ◽  
High Affinity ◽  
Follow Up Study ◽  
Highly Sensitive

Abstract We have developed a highly sensitive radioimmunoassay of thyroxine and thyrotropin for mass screening for neonatal hypothyroidism. This assay involves a single disc (3 mm diameter) of dried blood on filter paper. The minimum detectable concentrations are 15 pg/tube (10 microgram/L) for thyroxine and 15 nano-int. units/tube (10 milli-int. units/L) for thyrotropin; intra- and interassay CV’s are < 15% in both assays. The high sensitivity of this method is due to use of labeled thyroxine with high specific activity (3 kCi/g) and of an anti-thyrotropin serum with high affinity (Keq = 7.8 × 10(11) L/mol). With this method, 11337 newborns were screened; a follow-up study revealed that only newborns with both high thyrotropin and low thyroxine concentrations had permanent hypothyroidism. We conclude that this method is sensitive, simple, and reliable and that the recall rate with this method is much lower than that of tests for measuring thyroxine or thyrotropin alone.

Fragment D Immunoreacivity: The Influence of Iodination and Calcium Environment

1979 ◽  
Author(s):  
B. Kudryk ◽  
M. Blombäck
Keyword(s):  
Conformational Changes ◽  
Binding Sites ◽  
Specific Activity ◽  
High Specific Activity ◽  
Antigenic Determinants ◽  
Affinity Binding ◽  
Compact Structure ◽  
High Affinity Binding ◽  
High Affinity ◽  
Chloramine T

Human fragment D (Fg-Ds) has heen iodinated using both the Chloramine-T and lactoperoildaae methods. The specific activity was similar regardless of the method used. However, binding to a specific antibody was different for each preparation. The antigen labeled by the Chloramine-T method bound to a maximum of 40% the other labeled product bound up to 85%. A correlation between the decree of immunoreactivity and avidity for a fihrinmcnomer conjugate vas found also. Fibrinmonomer bound about twice the ajnount of lactoperoxidase iodinated Fg-Da ae it did the Chloramine-T product. The use of these conjugates in the purification of immunoreactive Fg-Ds of high specific activity will be discussed. High affinity binding sites for calcium have recently been demonstrated in fibrinogen. Tha presence of bound calcium is also believed to protect Fg-Ds f m further digestion by plasmin. This is probably due to the formation of a more compact structure. However, conformational changes for calcium bound fibrinogen or Fg-Ds have not been observed. We tested the immunoreactivity of the lactoperoxidase iodinated Fg-Ds in presence and absence of calcium. Differences were found and this data suggests that soma modification of antigenic determinants takes place as a consequence of calcium in the environment.

Measuring thyroxine and thyrotropin simultaneously in a dried blood sample on filter paper, to screen for neonatal hypothyroidism.

1980 ◽  
Vol 26 (6) ◽  
pp. 750-753 ◽  
Author(s):  
S Nagataki ◽  
K Ishibashi ◽  
R Ohsawa ◽  
S Suwa ◽  
N Tsukamoto ◽  
...  
Keyword(s):  
Filter Paper ◽  
Specific Activity ◽  
High Specific Activity ◽  
High Sensitivity ◽  
Recall Rate ◽  
Neonatal Hypothyroidism ◽  
High Affinity ◽  
Follow Up Study ◽  
Highly Sensitive

Abstract We have developed a highly sensitive radioimmunoassay of thyroxine and thyrotropin for mass screening for neonatal hypothyroidism. This assay involves a single disc (3 mm diameter) of dried blood on filter paper. The minimum detectable concentrations are 15 pg/tube (10 microgram/L) for thyroxine and 15 nano-int. units/tube (10 milli-int. units/L) for thyrotropin; intra- and interassay CV’s are < 15% in both assays. The high sensitivity of this method is due to use of labeled thyroxine with high specific activity (3 kCi/g) and of an anti-thyrotropin serum with high affinity (Keq = 7.8 × 10(11) L/mol). With this method, 11337 newborns were screened; a follow-up study revealed that only newborns with both high thyrotropin and low thyroxine concentrations had permanent hypothyroidism. We conclude that this method is sensitive, simple, and reliable and that the recall rate with this method is much lower than that of tests for measuring thyroxine or thyrotropin alone.

High-specific-activity 131iodine-metaiodobenzylguanidine for therapy of unresectable pheochromocytoma and paraganglioma

2021 ◽  
Author(s):  
Joseph S Dillon ◽  
David Bushnell ◽  
Douglas E Laux
Keyword(s):  
Biochemical Markers ◽  
Specific Activity ◽  
Locally Advanced ◽  
High Specific Activity ◽  
Anticancer Therapy ◽  
Biological Behavior ◽  
High Affinity ◽  
The Usa ◽  
Radiological Response ◽  
Mibg Therapy

Pheochromocytomas and paragangliomas (PPG) are rare cancers arising from the adrenal medulla (pheochromocytoma) or autonomic ganglia (paraganglioma). They have highly variable biological behavior. Most PPG express high affinity norepinephrine transporters, allowing active uptake of the norepinephrine analog, 131iodine-metaiodobenzylguanidine (131I-MIBG). Low-specific-activity forms of 131I-MIBG have been used since 1983 for therapy of PPG. High-specific-activity-131I-MIBG therapy improves hypertension management, induces partial radiological response or stable disease, decreases biochemical markers of disease activity and is well tolerated by patients. This drug, approved in the USA in July 2018, is the first approved agent for patients with unresectable, locally advanced or metastatic PPG and imaging evidence of metaiodobenzylguanidine uptake, who require systemic anticancer therapy.

[125I] 3-quinuclidinyl 4-iodobenzilate: A high affinity, high specific activity radioligand for the M1 and M2-acetylcholine receptors

Life Sciences ◽  
1984 ◽  
Vol 34 (23) ◽  
pp. 2287-2296 ◽  
Author(s):  
Raymond E. Gibson ◽  
Waclaw J. Rzeszotarski ◽  
Elaine M. Jagoda ◽  
Barbara E. Francis ◽  
Richard C. Reba ◽  
...  
Keyword(s):  
Acetylcholine Receptors ◽  
Specific Activity ◽  
High Specific Activity ◽  
High Affinity

Validation of a sensitive direct assay for melatonin for investigation of circadian rhythms in different species

1985 ◽  
Vol 106 (3) ◽  
pp. 387-394 ◽  
Author(s):  
G. E. Webley ◽  
H. Mehl ◽  
K. P. Willey
Keyword(s):  
Specific Activity ◽  
Biological Fluids ◽  
High Specific Activity ◽  
Male Rat ◽  
Rat Serum ◽  
Menstrual Cycles ◽  
High Affinity ◽  
Direct Assay ◽  
Wide Range

ABSTRACT The role of melatonin in animals which do not show marked seasonal changes in reproduction is disputed, in part because of the wide variation in reported concentrations. One reason for this may be the difficulties associated with the measurement of low molar concentrations of melatonin and the presence of a wide variety of potentially cross-reacting substances. The availability of a high affinity antiserum has allowed an assay, with low cross-reactivity and good sensitivity, to be established for the direct measurement of melatonin in a wide range of biological fluids, in particular serum, plasma and follicular fluid from man and rat. The high affinity of the antiserum enabled a tritium label of high specific activity to be used, removing the problems associated with the iodination of a small molecular weight compound. Melatonin concentrations in the assay were evaluated by four different methods: UV absorbance, gas chromatography, comparison of the immunoreactive concentrations of the label with the expected concentration by dilution and by comparison with a previously established assay which uses the same antiserum. Melatonin was measured in serum from twelve healthy women over two 24-h periods; eight women with normal menstrual cycles and four taking the contraceptive pill. Concentrations were found to range from 19·8 to 215 pmol/l during the day in both groups. In women with normal menstrual cycles peak concentrations of 513·2 ± 54·1 (s.e.m.) pmol/l were recorded at 04.00 h, whereas higher concentrations were found in women taking the pill, reaching a peak of 849·12 ± 21·8 (s.e.m.) pmol/l at 04.00 h. Similar melatonin concentrations were measured in the two 24-h periods. In the adult male rat, serum melatonin concentrations varied from 92·66 ± 37·9 (s.e.m.) pmol/l at 12.00 h, rising to 526 ± 55·6 (s.e.m.) pmol/l at 04.00 h. This direct assay is more practical and robust than the assays currently available. The careful validation of assay characteristics allows its widespread use in both clinical studies and the investigation of the role of melatonin in different species. J. Endocr. (1985) 106, 387–394

scholarly journals N-acetyl-2-aminofluorene (AAF) processing in adult rat hepatocytes in primary culture occurs by high-affinity low-velocity and low-affinity high-velocity AAF metabolite-forming systems

2017 ◽  
Author(s):  
K.S. Koch ◽  
T. Moran ◽  
W.T. Shier ◽  
H.L. Leffert
Keyword(s):  
High Velocity ◽  
Specific Activity ◽  
Culture Media ◽  
High Specific Activity ◽  
Metabolic Activation ◽  
Growth Cycle ◽  
Low Velocity ◽  
Metabolite Formation ◽  
Adult Rat ◽  
High Affinity

AbstractN-acetyl-2-aminofluorene (AAF) is a procarcinogen used widely in physiological investigations of chemical hepatocarcinogenesis. Its metabolic pathways have been described extensively, yet little is known about its biochemical processing, growth cycle expression and pharmacological properties inside living hepatocytes ‒ the principal cellular targets of this hepatocarcinogen. In this report, primary monolayer adult rat hepatocyte cultures and high specific-activity [ring G-3H]-N-acetyl-2-aminofluorene were used to extend previous observations of metabolic activation of AAF by highly differentiated, proliferation-competent hepatocytes in long-term cultures. AAF metabolism proceeded by zero-order kinetics. Hepatocytes processed significant amounts of procarcinogen (≈12 μg AAF/106cells/day). Five ring-hydroxylated and one deacylated species of AAF were secreted into the culture media. Extracellular metabolite levels varied during the growth cycle (days 0-13), but their rank quantitative order was time invariant: 5-OH-AAF > 7-OH-AAF > 3-OH-AAF > N-OH-AAF > aminofluorene (AF) > 1-OH-AAF. Lineweaver-Burk analyses revealed two principal classes of metabolism: System I (high-affinity and low-velocity), Km[APPARENT]= 1.64 × 10−7M and VMAX[APPARENT]= 0.1 nmols/106cells/day; and, System II (low-affinity and high-velocity), Km[APPARENT]= 3.25 × 10−5M and VMAX[APPARENT]= 1000 nmols/106cells/day. A third system of metabolism of AAF to AF, with Km[APPARENT]and VMAX[APPARENT]constants of 9.6 × 10−5M and 4.7 nmols/106cells/day, was also observed. Evidence provided in this report and its companion paper suggests selective roles and intracellular locations for System I- and System II-mediated AAF metabolite formation during hepatocarcinogenesis, although some of the molecules and mechanisms responsible for multi-system processing remain to be fully defined.

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