Two-Site Assays of Bone Gla Protein (Osteocalcin) Demonstrate Immunochemical Heterogeneity of the Intact Molecule

1992 ◽  
Vol 38 (11) ◽  
pp. 2318-2321 ◽  
Author(s):  
L J Deftos ◽  
R L Wolfert ◽  
C S Hill ◽  
D W Burton
Keyword(s):  
Renal Failure ◽  
Monoclonal Antibodies ◽  
Clinical Studies ◽  
Normal Subjects ◽  
Human Bone ◽  
Bone Gla Protein ◽  
Serum Concentrations ◽  
Paget Disease ◽  
Linear Sequence ◽  
Intact Molecule

Abstract We developed a panel of monoclonal antibodies to human bone gla protein (BGP; osteocalcin) peptides that span the linear sequence of the molecule, specifically BGP 1-12 (N-terminal), BGP 15-30 (midregion), and BGP 38-49 (C-terminal). These antibodies were evaluated in various combinations of two-site formats in studies of serum BGP concentrations. For clinical studies, we selected from a panel of antibodies the two most sensitive antibody pairs for the intact molecule (N-C); we also used a polyclonal RIA based on BGP-C. For the two-site format, we used two N-terminal antibodies, 029 and 052, adsorbed to polystyrene beads, and radioiodinated a C-terminal antibody, 663. The standard for each of the assays was purified human BGP. The following BGP serum concentrations (microgram/L, mean +/- SE) were measured with the various assays: by the 029-663 assay, results for normal subjects were 7 +/- 3, for patients with renal failure 25 +/- 8, and for patients with Paget disease 12 +/-4; by the 052-663 assay, the respective results were 22 +/- 4, 44 +/- 12, and 31 +/- 7; by the polyclonal assay, the results were 3 +/- 0.2, 13 +/- 2, and 5 +/- 1. The two intact (N-C) assays were significantly (P < 0.01) correlated (r = 0.94), but their serum values differed by more than twofold in terms of the same BGP standard. The polyclonal assay significantly correlated with each of the intact assays (r = 0.83, 0.77), but it, too, gave different serum values for BGP. These studies demonstrate the immunochemical heterogeneity of circulating BGP, heterogeneity that is manifest even in immunoassays specific for the same region of the molecule.

A radioimmunoassay for bone Gla protein (BGP) in human plasma

1987 ◽  
Vol 114 (3) ◽  
pp. 410-416 ◽  
Author(s):  
Julia S. Johansen ◽  
J. E. Mølholm Hansen ◽  
Claus Christiansen
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Human Plasma ◽  
Biochemical Marker ◽  
Normal Subjects ◽  
Bone Gla Protein ◽  
Low Concentrations ◽  
Metabolic Bone ◽  
The Mean ◽  
Bone Physiology

Abstract. To study the value of bone Gla protein (BGP) as a biochemical marker of normal bone physiology and metabolic bone disorders, we have developed a radioimmunoassay (RIA) for the detection of BGP in human plasma. Antibodies were generated in rabbits immunized with purified calf BGP conjugated to thyroglobulin. Human plasma BGP reacted identically with the calf BGP standard, thus demonstrating the suitability of the assay to measure plasma BGP levels in man. The RIA is sensitive, accurate, and technically simple. Plasma BGP levels were determined in normal subjects (N = 35) and in patients with hypothyroidism (N = 10), hyperthyroidism (N = 22) and chronic renal failure (N = 35). The mean (± 1 sem) concentration of plasma BGP in normal subjects was 1.27 ± 0.07 nmol/l. Plasma BGP was significantly increased in patients with hyperthyroidism, 4.04 ± 0.78 nmol/l (P < 0.001) and chronic renal failure, 10.17 ± 2.47 nmol/l (P < 0.001). Low concentrations were found in patients with hypothyroidism, 0.74 ± 0.11 nmol/l (P <0.01). Our studies indicate that plasma BGP provides a useful technique in the diagnosis of patients with bone disease.

Evidence for an Increased Generation of Prostacyclin in the Microvasculature and an Impairment of the Platelet α-Granule Release in Chronic Renal Failure

1988 ◽  
Vol 60 (02) ◽  
pp. 205-208 ◽  
Author(s):  
Paul A Kyrle ◽  
Felix Stockenhuber ◽  
Brigitte Brenner ◽  
Heinz Gössinger ◽  
Christian Korninger ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Blood Clotting ◽  
Normal Subjects ◽  
Chronic Uraemia ◽  
Wall Interaction ◽  
End Stage ◽  
Granule Release

SummaryThe formation of prostacyclin (PGI2) and thromboxane A2 and the release of beta-thromboglobulin (beta-TG) at the site of platelet-vessel wall interaction, i.e. in blood emerging from a standardized injury of the micro vasculature made to determine bleeding time, was studied in patients with end-stage chronic renal failure undergoing regular haemodialysis and in normal subjects. In the uraemic patients, levels of 6-keto-prostaglandin F1α (6-keto-PGF1α) were 1.3-fold to 6.3-fold higher than the corresponding values in the control subjects indicating an increased PGI2 formation in chronic uraemia. Formation of thromboxane B2 (TxB2) at the site of plug formation in vivo and during whole blood clotting in vitro was similar in the uraemic subjects and in the normals excluding a major defect in platelet prostaglandin metabolism in chronic renal failure. Significantly smaller amounts of beta-TG were found in blood obtained from the site of vascular injury as well as after in vitro blood clotting in patients with chronic renal failure indicating an impairment of the a-granule release in chronic uraemia. We therefore conclude that the haemorrhagic diathesis commonly seen in patients with chronic renal failure is - at least partially - due to an acquired defect of the platelet a-granule release and an increased generation of PGI2 in the micro vasculature.

Plasma D Dimer: A Useful Marker of Fibrin Breakdown in Renal Failure

1989 ◽  
Vol 61 (03) ◽  
pp. 522-525 ◽  
Author(s):  
M P Gordge ◽  
R W Faint ◽  
P B Rylance ◽  
H Ireland ◽  
D A Lane ◽  
...  
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Acute Renal Failure ◽  
Monoclonal Antibodies ◽  
Diabetic Nephropathy ◽  
Renal Disease ◽  
Plasma Concentrations ◽  
Significant Negative Correlation ◽  
Healthy Controls ◽  
D Dimer

SummaryD dimer and other large fragments produced during the breakdown of crosslinked fibrin may be measured by enzyme immunoassay using monoclonal antibodies. In 91 patients with renal disease and varying degrees of renal dysfunction, plasma D dimer showed no correlation with renal function, whereas FgE antigen, a fibrinogen derivative which is known to be cleared in part by the kidney, showed a significant negative correlation with creatinine clearance. Plasma concentrations of D dimer were, however, increased in patients with chronic renal failure (244 ± 3l ng/ml) (mean ± SEM) and diabetic nephropathy (308 ± 74 ng/ml), when compared with healthy controls (96 ± 13 ng/ml), and grossly elevated in patients with acute renal failure (2,451 ± 1,007 ng/ml). The results indicate an increase in fibrin formation and lysis, and not simply reduced elimination of D dimer by the kidneys, and are further evidence of activated coagulation in renal disease. D dimer appears to be a useful marker of fibrin breakdown in renal failure.

Endogenous digoxin-like immunoreactive factors: impact on digoxin measurements and potential physiological implications.

1985 ◽  
Vol 31 (9) ◽  
pp. 1525-1532 ◽  
Author(s):  
R Valdes
Keyword(s):  
Renal Failure ◽  
Liver Failure ◽  
Pregnant Women ◽  
Serum Proteins ◽  
Newborn Infants ◽  
Normal Subjects ◽  
Carrier Proteins ◽  
Third Trimester ◽  
Weakly Bound ◽  
Urine And Serum

Abstract Various laboratories have reported endogenous digoxin-like immunoreactive factor(s) (DLIF) in blood from patients in renal failure or liver failure, from newborn infants, and from third-trimester pregnant women. Similar immunoreactivity has been detected in amniotic fluid, in cord blood, and in urine and serum from normal subjects. The factor(s) giving rise to this immunoreactivity cross react with antibodies used in many currently available immunoassays for digoxin, sometimes causing apparent digoxin concentrations exceeding the therapeutic range obtained for exogenous digoxin, with consequent errors in measurement and in subsequent clinical interpretation of digoxin results. Here, I summarize findings in our laboratory and those of others. DLIF evidently exist in three states in serum: tightly protein-bound, weakly protein-bound, and unbound (free). In normal subjects, greater than 90% of the total DLIF in serum is tightly but reversibly bound to serum proteins and is not readily detectable by direct measurement of digoxin in serum with conventional immunoassays. However, there seems to be a redistribution of the more weakly bound and unbound components in patients with renal failure, pregnant women, and newborns. The increased values detected in these groups are ascribable to increased amounts of weakly bound and unbound DLIF rather than to increased total DLIF. Carrier proteins may play a prominent role in the transport of these factors in blood. I discuss the potential physiological and pharmacological implications of detecting endogenous immunoreactive factors that cross react with antibodies to drugs.

Pharmacokinetics and effect on blood pressure of doxazosin in normal subjects and patients with renal failure

1986 ◽  
Vol 40 (5) ◽  
pp. 561-566 ◽  
Author(s):  
Robert V Carlson ◽  
Ross R Bailey ◽  
Evan J Begg ◽  
Marion G Cowlishaw ◽  
John R Sharman
Keyword(s):  
Blood Pressure ◽  
Renal Failure ◽  
Normal Subjects

A Study on the Distribution of Body Fluids after Rapid Saline Expansion in Normal Subjects and in Patients with Renal Insufficiency: Preferential Intravascular Deposition in Renal Failure

1983 ◽  
Vol 64 (2) ◽  
pp. 153-160 ◽  
Author(s):  
Hendrik A. Koomans ◽  
Anton B. Geers ◽  
Peter Boer ◽  
Jan C. Roos ◽  
Evert J. Dorhout Mees
Keyword(s):  
Renal Failure ◽  
Blood Volume ◽  
Plasma Volume ◽  
Extracellular Fluid ◽  
Normal Subjects ◽  
Distribution Volume ◽  
Fluid Distribution ◽  
Severe Renal Failure ◽  
Control Value ◽  
Stage Renal Disease

1. The effect of rapid intravenous infusion of 25 ml of isotonic sodium chloride solution (saline)/kg body weight on extracellular fluid volume (ECFV, 82Br distribution volume), plasma volume (131I-labelled albumin distribution volume) and blood volume (from plasma volume and packed cell volume) was studied in nine normal subjects and a group of 11 patients with end-stage renal disease (ESRD). 2. Immediately after the infusion, the increases in ECFV were equal in the two groups but the increases in plasma and blood volumes were significantly larger in the patients with ESRD. .3. Ninety minutes after the end of the infusion, the blood volume/ECFV ratio was significantly decreased from the control value in the normal subjects, but slightly increased in the patients with ESRD. 4. It is concluded that in severe renal failure the control of fluid distribution is changed in a way which leads to a preferential distribution of rapidly infused saline into the intravascular compartment.

Elotuzumab in the treatment of relapsed and refractory multiple myeloma

2021 ◽  
Author(s):  
Sebastian Grosicki ◽  
Martyna Bednarczyk ◽  
Agnieszka Barchnicka ◽  
Olga Grosicka
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Natural Killer Cells ◽  
Natural Killer ◽  
Clinical Studies ◽  
Mechanisms Of Action ◽  
Incurable Disease ◽  
The Us ◽  
Us Fda ◽  
Humanized Monoclonal Antibodies

Multiple myeloma (MM) is still considered an incurable disease. However, drugs with different mechanisms of action that can improve the efficiency of treatment offer hope. Still, there are concerns about an unacceptable increase in toxicity with such regimens. The results of recently published clinical studies of elotuzumab in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone confirm previous hopes to improve the effect of that treatment. Humanized monoclonal antibodies aimed at SLAMF7 stimulate natural killer cells to fight against MM cells. Elotuzumab used in combination with lenalidomide/dexamethasone or with pomalidomide/dexamethasone is approved by the US FDA to treat patients with relapsed and/or refractory MM. The article is a summary of the recent knowledge about the possibility of using elotuzumab in the treatment of relapsed and/or refractory MM and shows its potential uses in the future.

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