scholarly journals Total folate binding capacity of normal human plasma, and variations in uremia, cirrhosis, and pregnancy

Blood ◽  
1976 ◽  
Vol 48 (6) ◽  
pp. 911-921 ◽  
Author(s):  
N Colman ◽  
V Herbert
Keyword(s):  
Lactobacillus Casei ◽  
Binding Capacity ◽  
Gel Filtration ◽  
Normal Subjects ◽  
Serum Folate ◽  
Folate Level ◽  
High Affinity ◽  
Serum Folate Level ◽  
Normal Human ◽  
Clinical Conditions

Abstract The current study presents evidence that all human serum contains a class of high-affinity folate binders (KA=2.8 X10(10 liters/mole), which migrate as a single peak on gel filtration. Failure of previous studies to detect this characteristic in all but a minority of subjects is attributable to its variable, often total, saturation. Direct measurement of the total folate binding capacity (TFBC) has been made possible by dissociation of endogenous folate-binder complexes at acid pH, removal of free folate by coated charcoal, and radiofolate tagging. This procedure does not appear to significantly denature the binders, which release and rebind similar quantities of 3H-PGA. In 20 normal subjects, TFBC ranged from 100 to 325 pg/ml (mean+/-SE = 174+/-16), and was always at least 33% saturated. In three clinical conditions, all associated with elevated unsaturated folate binding capacity, three different patterns emerged when TFBC was also measured. Uremic subjects had significantly elevated mean TFBC with normal saturation. In cirrhotic subjects, mean TFBC approximated normal, but saturation was significantly decreased. In pregnancy, two groups were seen: one with increased TFBC and the other with a normal TFBC, some of whom had decreased saturation. Lactobacillus casei serum folate level was about 30 times greater than the TFBC; there was no correlation between the two measurements.

scholarly journals Total folate binding capacity of normal human plasma, and variations in uremia, cirrhosis, and pregnancy

Blood ◽  
1976 ◽  
Vol 48 (6) ◽  
pp. 911-921 ◽  
Author(s):  
N Colman ◽  
V Herbert
Keyword(s):  
Lactobacillus Casei ◽  
Binding Capacity ◽  
Gel Filtration ◽  
Normal Subjects ◽  
Serum Folate ◽  
Folate Level ◽  
High Affinity ◽  
Serum Folate Level ◽  
Normal Human ◽  
Clinical Conditions

The current study presents evidence that all human serum contains a class of high-affinity folate binders (KA=2.8 X10(10 liters/mole), which migrate as a single peak on gel filtration. Failure of previous studies to detect this characteristic in all but a minority of subjects is attributable to its variable, often total, saturation. Direct measurement of the total folate binding capacity (TFBC) has been made possible by dissociation of endogenous folate-binder complexes at acid pH, removal of free folate by coated charcoal, and radiofolate tagging. This procedure does not appear to significantly denature the binders, which release and rebind similar quantities of 3H-PGA. In 20 normal subjects, TFBC ranged from 100 to 325 pg/ml (mean+/-SE = 174+/-16), and was always at least 33% saturated. In three clinical conditions, all associated with elevated unsaturated folate binding capacity, three different patterns emerged when TFBC was also measured. Uremic subjects had significantly elevated mean TFBC with normal saturation. In cirrhotic subjects, mean TFBC approximated normal, but saturation was significantly decreased. In pregnancy, two groups were seen: one with increased TFBC and the other with a normal TFBC, some of whom had decreased saturation. Lactobacillus casei serum folate level was about 30 times greater than the TFBC; there was no correlation between the two measurements.

scholarly journals Clinical and laboratory observations on serum folate-binding protein

Blood ◽  
1975 ◽  
Vol 46 (4) ◽  
pp. 599-609 ◽  
Author(s):  
ER Eichner ◽  
CJ Paine ◽  
VL Dickson ◽  
MD Jr Hargrove
Keyword(s):  
Binding Protein ◽  
Elevated Serum ◽  
Normal Subjects ◽  
Serum Levels ◽  
Serum Folate ◽  
Folate Level ◽  
Folate Binding Protein ◽  
Serum Folate Level ◽  
Relationship Of ◽  
The Relationship

Abstract We studied the effect of serum folate-binding protein (FBP) on folate radioassays and the relationship of the serum level of unsaturated FBP to the serum folate level in various clinical states. Our modification of a heat-extracted radioassay was compared to a whole serum radioassay. Our results confirmed the existence of elevated serum levels of unsaturated FBP in some normal subjects, in some women taking oral contraceptives, and in most patients with uremia. Elevated levels of unsaturated FBP will produce falsely low results in folate radioassay unless the FBP has been destroyed by heat, as was done in the modified radioassay here presented. In normal and uremic subjects, serum folate and unsaturated FBP levels tended to correlate, whereas in patients taking large doses of folic acid the level of unsaturated FBP fell as the level of serum folate rose.

scholarly journals Clinical and laboratory observations on serum folate-binding protein

Blood ◽  
1975 ◽  
Vol 46 (4) ◽  
pp. 599-609
Author(s):  
ER Eichner ◽  
CJ Paine ◽  
VL Dickson ◽  
MD Jr Hargrove
Keyword(s):  
Binding Protein ◽  
Elevated Serum ◽  
Normal Subjects ◽  
Serum Levels ◽  
Serum Folate ◽  
Folate Level ◽  
Folate Binding Protein ◽  
Serum Folate Level ◽  
Relationship Of ◽  
The Relationship

We studied the effect of serum folate-binding protein (FBP) on folate radioassays and the relationship of the serum level of unsaturated FBP to the serum folate level in various clinical states. Our modification of a heat-extracted radioassay was compared to a whole serum radioassay. Our results confirmed the existence of elevated serum levels of unsaturated FBP in some normal subjects, in some women taking oral contraceptives, and in most patients with uremia. Elevated levels of unsaturated FBP will produce falsely low results in folate radioassay unless the FBP has been destroyed by heat, as was done in the modified radioassay here presented. In normal and uremic subjects, serum folate and unsaturated FBP levels tended to correlate, whereas in patients taking large doses of folic acid the level of unsaturated FBP fell as the level of serum folate rose.

Determination of Unbound Bilirubin in the Serum of Newborns

1974 ◽  
Vol 20 (7) ◽  
pp. 783-789 ◽  
Author(s):  
Jorgen Jacobsen ◽  
Richard P Wennberg
Keyword(s):  
Binding Capacity ◽  
Newborn Infants ◽  
Albumin Binding ◽  
Initial Oxidation ◽  
High Affinity ◽  
Normal Human ◽  
Unbound Bilirubin ◽  
Rate Limiting

Abstract An enzymatic assay is described for non-albuminbound bilirubin in the serum of newborn infants. Unbound bilirubin is oxidized to colorless compounds by ethyl hydroperoxide in the presence of horseradish peroxidase (EC 1.11.1.7), while albumin-bound bilirubin is protected from oxidation. Because the equilibrium between albumin and bilirubin occurs rapidly, the oxidation step is rate limiting, and the initial oxidation velocity of total bilirubin is proportional to the unbound bilirubin concentration. By titrating serum with bilirubin in vitro, the association constant and binding capacity of high-affinity sites for albumin binding can be determined. Normal human serum albumin tightly binds 1 mole of bilirubin per mole of albumin (binding constant, 2-4 x 108 liter/mol). Although weaker secondary binding occurs, the unbound bilirubin fraction increases rapidly after the high-affinity binding sites are saturated. Compromised newborns may have a decreased apparent binding capacity and (or) binding affinity. The method can be used to assess the risk of a jaundiced infant for bilirubin encephalopathy.

IMMUNOREACTIVE GROWTH HORMONE IN HUMAN URINE

1972 ◽  
Vol 71 (4) ◽  
pp. 665-676 ◽  
Author(s):  
Kristian F. Hanssen
Keyword(s):  
Molecular Weight ◽  
Growth Hormone ◽  
Linear Relationship ◽  
Human Urine ◽  
Gel Filtration ◽  
Human Growth ◽  
Normal Subjects ◽  
Normal Human ◽  
Radio Immunoassay

ABSTRACT By using a double antibody radio-immunoassay (pre-precipitation technique) for the determination of immunoreactive human growth hormone (IRHGH) in normal human urine concentrated by dialysis and lyophilization, a factor was revealed that displaces 125I-HGH from HGH antibodies. This displacement was neither due to salts nor to glucose; it is suggested that it is due to IRHGH in the urine. A linear relationship between dilution of urine and the measured IRHGH concentration was obtained. Recovery of exogenous HGH was between 70–105%. The recovery of IRHGH from different volumes of urine following dialysis and lyophilization was between 97–110%. Plasma IRHGH and urinary IRHGH was measured simultaneously after HGH injection in a normal subject. A correlation was shown between plasma IRHGH and urinary IRHGH. In 9 normal subjects, the urinary IRHGH ranged from 28–53 ng/24 h. The excretion of urinary IRHGH was increased in acromegaly and was diminished in some, but not in all patients with adult hypopituitarism. The urinary IRHGH was further studied by gel filtration. It was recovered in one peak corresponding to a molecular weight of approximately 20 000 – 30 000. However, in the present work it was not clarified whether the urinary IRHGH represents pituitary HGH excreted in the urine or a metabolite of high molecular weight with retained immunological properties.

scholarly journals Isolation and characterization of membrane proteins responsible for attachment of polyribosomes to rough microsomal fraction of rat liver

1977 ◽  
Vol 164 (1) ◽  
pp. 53-66 ◽  
Author(s):  
S Fujita ◽  
F Ogata ◽  
J Nakamura ◽  
S Omata ◽  
H Sugano
Keyword(s):  
Rat Liver ◽  
Protein Fraction ◽  
Microsomal Fraction ◽  
Binding Capacity ◽  
Gel Filtration ◽  
High Affinity ◽  
Isolation And Characterization ◽  
Microsomal Membranes ◽  
Equilibrium Centrifugation

A protein fraction which has a high affinity for polyribosomes was isolated from rough microsomal membranes of rat liver. The mode of polyribosome binding to this fraction (R-fraction) was studied by using CsCl equilibrium centrifugation and compared with that for stripped rough microsomal membranes. The following were found. (1) The polyribosome-binding cpacity of the R-fraction was heat-labile and sensitive to trypsin, and was suppressed by increasing KCl concentration and addition of 0.1 mM-aurintricarboxylic acid. (2) Of the four subfractions obtained by gel filtration of the R-fraction on a Sephadex G-200, only the R1-fraction, eluted at the void volume, showed a high affinity for polyribosomes. The polyribosome-binding capacity of the R1-fraction decreased with time on storage at 4 degrees C. (3) The R1-fraction contained three major proteins with mol. wts. 108,000, 99,000 and 65,000.

Pre-treatment serum folate levels and toxicity in colorectal cancer patients treated with 5-fluorouracil and folinic acid.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 755-755 ◽  
Author(s):  
Michael Yan ◽  
Mark David Vincent ◽  
Cheryl Ho ◽  
Eric Winquist ◽  
Derek J. Jonker ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Folinic Acid ◽  
Cancer Patients ◽  
Serum Folate ◽  
Folate Level ◽  
Serum Folate Level ◽  
Pre Treatment ◽  
Grade 3 ◽  
Colorectal Cancer Patients ◽  
Schedule Modification

755 Background: 5-fluorouracil (5-FU) chemotherapy is associated with severe and unpredictable toxicity in a significant proportion of patients.We hypothesized that susceptibility to 5-FU toxicity might be related to individual differences in components of reduced folate metabolism affecting intracellular 5,10-MTHF levels, detectable in blood prior to treatment. Methods: A prospective cohort of chemo-naive colorectal cancer patients planned to receive IV 5-FU and folinic acid for five consecutive days every four weeks were studied. Baseline clinical and laboratory data were collected prior to treatment. Biochemical data associated with folate metabolism was also collected and not revealed to treating physicians. The primary endpoint was occurrence of > grade 3 toxicity and/or toxicity mandating dose delay or reduction. Results: Of 78 eligible patients studied, 68% experienced > grade 3 toxicity, 69% had schedule modification, and 81% had either or both. Multivariable analyses identified only a higher pre-treatment serum folate level as an independent predictor of toxicity > grade 3 and/or mandating schedule modification (p = 0.016). An increasing toxicity trend was observed amongst folate-stratified patient cohorts, with an odds ratio of 2.87 (p = 0.09) comparing the highest and lowest quartiles. Concurrently, overall survival and relapse-free rates also increased with pretreatment folate levels in the adjuvant cohort with log rank values of 3.60 (p = 0.06) and 7.20 (p = 0.007) between the highest quartile and the lower quartiles, respectively. Conclusions: The incidence of severe toxicity with this schedule of 5-FU and folinic acid was high and positively correlated with the pretreatment serum folate level. Interestingly, a concurrent increase in overall and relapse free survival is observed with increasing serum folate levels. These results suggest that an optimal pretreatment folate level exists that balances chemotherapy treatment efficacy and toxicity.

FACTORS AFFECTING THE BINDING OF CORTISOL BY TRANSCORTIN

1963 ◽  
Vol 44 (1) ◽  
pp. 107-118 ◽  
Author(s):  
P. De Moor ◽  
O. Steeno ◽  
R. Deckx
Keyword(s):  
Binding Capacity ◽  
Gel Filtration ◽  
Normal Subjects ◽  
Unbound Fraction ◽  
Factors Affecting ◽  
Series Of Experiments ◽  
Normal Males ◽  
Low Cortisol ◽  
Rule Out

ABSTRACT By means of a gel filtration on Sephadex columns the plasma corticoids can be separated into two fractions: namely a fraction bound to a macromolecular agent and an unbound fraction. When plasma is overloaded with cortisol before gel filtration, the binding capacity of the macromolecular agent can be evaluated. The bound corticoids can be measured quantitatively either fluorimetrically or colorimetrically. The macromolecular binding agent behaves like transcortin in a series of experiments. Various exogenous and endogenous steroids are known to influence transcortin activity in vivo. Methylestrenolone and lynestrenol administered orally to normal males or to women with various gynaecological conditions did not significantly increase the cortisol binding capacity. Intravenous administration of Metopirone lowered the cortisol binding capacity in normal subjects but not in a patient with hypophysial insufficiency. Attempts were made to remove steroids from plasma without destroying transcortin, in order to rule out any possible interference with the cortisol binding process by other steroids. Extraction of plasma with organic solvents either at room temperature or at minus 25° C irreversibly destroyed most of the transcortin. Dialysis of plasma against a 1% solution of bovine albumin (40 volumes) for 12 h at 40° C decreased the unconjugated corticoid level by 63%. This procedure did not alter transcortin activity in the plasma of normal adults, in umbilical cord blood, in pregnancy plasma or in the plasma of obese patients with a low cortisol binding capacity. However, the lowering in C.B.C. observed in the plasma of patients treated with Metopirone could be partly abolished by this procedure. Although the extraction experiments at low temperature suggested the existence of a lipid-link in the cortisol binding system of human plasma, this could not be demonstrated.

ORAL CONTRACEPTIVES AND SERUM-FOLATE LEVEL

The Lancet ◽  
1968 ◽  
Vol 291 (7556) ◽  
pp. 1376-1377 ◽  
Author(s):  
A Majid Shojania ◽  
Gloria Hornady ◽  
PhilipH Barnes
Keyword(s):  
Oral Contraceptives ◽  
Serum Folate ◽  
Folate Level ◽  
Serum Folate Level
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