Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lower concentrations of total serum zinc (540 +/- 111 mug/1, mean +/- SEM), and of albumin-bound serum zinc (295 +/- 113 mug/1) and a higher concentration of alpha2-macroglobulin-bound zinc (245 +/- 69 mug/1) were found in 25 patients with decompensated hepatic cirrhosis, compared to 28 healthy subjects (835 +/- 91; 679 +/- 83; 156 +/- 27 mug/1 respectively). Levels of total and albumin-bound zinc were significantly and positively correlated with serum albumin levels. Higher levels of alpha2-macroglobulin-bound zinc were associated with higher levels of alpha2-macroglobulin in these patients (2.8 +/- 0.8 g/1) compared to normals (2.3 +/- 0.6). Hence, not only do decompensated cirrhotics exhibit a lower serum zinc level but a greater proportion of this zinc is associated with the tightly bound, and presumably metabolically more inert, serum fraction. This situation exaggerates the zinc deficiency state of the severe cirrhotic.
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PMID:Distribution of serum zinc between albumin and alpha2-macroglobulin in patients with decompensated hepatic cirrhosis. 5 58

Surgical samples of human prostate were explanted and submitted to constant-flow organ culture. The medium contained 3H-testosterone 50 nM, and except for controls, increasing concentrations of human serum albumin (HSA) or human sex-steroid-binding plasma protein (SBP). At steady state, the explants were washed and homogenized, and the total radioactivity, radioactive testosterone, androstanolone (17 beta-hydroxyandrostan-3-one), androstane-3 alpha, 17 beta-diol, and androstane-3 beta, 17 beta-diol were determined after the addition of the corresponding internal 14C standards. From these data, testosterone uptake and metabolism were quantitated. The concentration of unbound testosterone in protein-supplemented culture media was measured separately by equilibrium dialysis. In control superfusions without protein, the tissue concentration of total radioactive steroids was equivalent to 182 +/- 18 (mean +/- SEM) pmoles/g of prostate. Androstanolone represented about 2/3, testosterone 1/10, and the two androstanediols together 1/10 of the total radioactivity. No difference was found between "normal" and hyperplastic prostate explants. In experiments with HSA (15-176 muM), is was observed that the uptake of radioactive testosterone in the prostate explants was decreased in direct proportion to the unbound testosterone fraction of the superfusion medium, but the proportions of testosterone metabolities in the superfused explants remained the same. In experiments with SBP (6-135 nM), the concentrations of unbound testosterone in the superfusion medium were reduced to the same levels as in the experiments with HSA. The reduction of tissue radioactivity was somewhat larger than that expected from the reduction of unbound testosterone in the superfusion medium for the concentrations of SBP less than 50 nM, and then remained approximately constant. In addition, SBP altered the metabolism of testosterone: the androstanolone/testosterone ratio in the prostate explants was critically dependent upon the SBP concentration in the superfusion medium. It is therefore suggested that, independent of its effect on the binding of testosterone, SBP has a direct effect on testosterone uptake and metabolism by the human prostate. The underlying mechanism is unknown.
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PMID:Influence of purified plasma proteins on testosterone uptake and metabolism by normal and hyperplastic human prostate in "constant-flow organ culture". 5 32

The transfer and metabolism of cortisol and cortisone and the effect of protein binding on these processes have been investigated in vitro in the perfused human placenta. The clearance of cortisol in buffer, expressed as a fraction of the antipyrine transfer rate (clearance index), was 0.50 +/- 0.05 SEM in either direction. Extensive conversion to cortisone (85%) occurred during transfer. Addition of corticosteroid-binding globulin (CBG) in amounts sufficient to bind 50% of the cortisol reduced the clearance (0.40 +/- .026) insignificantly, whereas human serum albumin (HSA) in amounts sufficient to bind 50% of the cortisol reduced the clearance to 0.28 +/- 0.012 (P less than 0.001) even though the association constant for albumin is approximately 1000-fold less. The percent of conversion to cortisone did not change significantly with protein binding. The clearance index of cortisone from a protein-free perfusate was 0.74. With CBG and albumin in the same concentrations as used in the cortisol experiments, the binding of cortisone to CBG was 23% and its clearance was 0.70; with albumin, the binding was 45% and the clearance index was 0.45. The addition of albumin and CBG to the same perfusate resulted in a cortisol clearance equal to that obtained with perfusate containing only albumin. Binding to albumin may be more significant than binding to CBG in controlling the transfer rate of cortisol to the fetus.
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PMID:Effect of protein binding on transfer and metabolism of cortisol in perfused human placenta. 26 69

21 patients with gastroenterological disease and indication for the use of intravenous nutrition received an elemental diet (ED) for 5-44 days. In 6 out of 8 patients with exacerbation of Crohn's disease remissions were achieved, apart from 3 persistent fistulas. In 5 out of 9 cases with various primary diseases and postoperative intestinal fistulas, spontaneous healing was observed. Furthermore, 2 patients with ulcerative colitis, 1 with radiation enteritis and 1 with pancreatitis were treated with ED. On ED, hemoglobin increased from 11.3 +/- 0.4 (m +/- SEM) to 12.0 +/- 0.5 g% (p less than 0.01) and serum albumin from 2.7 +/- 0.1 to 3.4 +/- 0.1 g% (p less than 0.001). Nitrogen requirements were studied in 11 patients receiving various quantities of ED. Nitrogen balance was found to be in equilibrium or positive in 7 patients, and negative in 4. In one patient with severe ulcerative colitis, fecal nitrogen losses were higher than urinary nitrogen losses. The unpleasant taste of ED resulting from free amino acids limited the ED supply in 3 patients and led to premature ending of ED administration in 3 other patients. In such cases ED may be given by nasogastric tube feeding. From the results presented it appears that ED is indicated in Crohn's disease and intestinal fistulas. However, the results obtained require confirmation by further observations and comparison with an intravenously fed control group.
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PMID:[Elementary diet as an alternative to parenteral feeding in severe gastrointestinal diseases]. 40 20

1 alpha, 25-Dihydroxycholecalciferol (1,25-(OH)2D3) has been measured in human serum by radioimmunoassay. The assay uses a high titre antiserum raised in sheep against 1,25-(OH)2D3-25-hemisuccinate, conjugated to bovine serum albumin. The sensitivity of the assay is 10 pg/tube. Other hydroxylated forms of vitamin D3 cross react with the antiserum and are therefore removed from serum extracts by chromatography on Sephadex LH 20 followed by high pressure liquid chromatography. The mean (+/- SEM) serum 1,25-(OH)2D3 concentration for a group of healthy adult subjects was 41 +/- 2.5 pg/ml. None was detected in anephric patients and the concentration was low or undetectable in patients with chronic renal failure.
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PMID:Measurement of 1,25-dihydroxycholecalciferol in man by radioimmunoassay. 48 20

In a group of 18 inpatients, the catabolism of serum albumin rate, in percentage of intravascular albumin pool, was measured during two successive periods of 7 days. In the first experimental period, we did no intubation, while during the second, a tube was kept in the stomach, with an overnight intragastric perfusion of an isotonic solution of sodium bicarbonate. With the same batches of labelled albumin, we measured the serum albumin catabolism, in a similar way, in a group of 19 normal subjects, for two weeks, without gastric intubation. The difference in the rate of serum albumin catabolism, during the first and second period, is positive and amounts to +0.547 percent +/- 0.214 (mean +/- SEM) in the intubated group, and +0.765 percent +/- 0.207 in the control group. The weaker decrease in catabolism rate during the second period in the intubated group, as compared to the control group, is not statistically significant (t = 0.731). We conclude that continuous intubation of the stomach for 7 days does not increase the catabolism rate of serum albumin. Therefore, it should not significantly increase the loss of albumin in the gastric lumen.
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PMID:Effect of gastric intubation of the gastric loss of serum albumin. 68 47

High titer antibodies to secretin were produced in rabbits by immunization with purified porcine secretin (from GIH) conjugated to bovine serum albumin in complete Freund's adjuvant. Synthetic porcine secretin (from Squibb) was radiolabeled with 125I using chloramine-T and radiosecretin was purified using talc-silica and fibrocellulose powder. Specificity of antibodies to secretin was extensively evaluated in studies examining (1) cross-reactivity with other naturally occurring hormones, (2) parellelism of serum dilutions and secretin standards, (3) quantitative recovery of secretin added to serum samples, and (4) changes in circulating immunoreactive secretin in response to intraduodenal acidification. The mean fasting serum secretin concentration in 10 dogs was 65 +/- 5 (SEM) pg per ml and in 21 healthy human volunteers it was 69 +/- 5 pg per ml. In response to intraduodenal instillation of 10 mEq of HCl, portal venous secretin concentrations increased from a mean fasting value of 52 to 450 pg per ml within 2 min; peripheral venous secretin increased from 66 to 229 pg per ml within 5 min. No significant changes in peripheral serum immunoreactive secretin concentrations were identified in dogs after a protein meal. Intravenously administered secretin in man disappeared from the circulation with mean half-life 4.06 +/- 0.82 (SEM) min.
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PMID:Radioimmunoassay measurement of secretin half-life in man. 83 Feb 38

The effects of Fab fragments of high-affinity specific antibodies have been studied in a canine experimental model of lethal digitoxin toxicity. Selected antiserum from sheep immunized and boosted with a digoxin-serum albumin conjugate contained antibodies that cross-reacted with digitoxin with an average intrinsic association constant of 1.4 x 10(10) M(-1) as determined by equilibrium dialysis. Rapid second-order association kinetics (k(f) = 3.7 x 10(6) M(-1) per s) and slow dissociation kinetics (k(r) = 1.9 x 10(-4) per s) were documented for the antibody-digitoxin complex. Eight dogs given 0.5 mg/kg digitoxin intravenously developed ventricular tachycardia after 23+/-4 (SEM) min. Control nonspecific Fab fragments were then given. All animals died an average of 101+/-36 min after digitoxin administration. Another eight dogs given the same digitoxin dose similarly developed ventricular tachycardia after 28+/-3 min. This group then received a molar equivalent dose of specific Fab fragments intravenously over 3 min, followed by a 30-min infusion of one-third of the initial dose. All dogs survived. Conducted sinus beats reappeared 18+/-4 min after initial Fab infusion, and stable normal sinus rhythm was present at 54+/-16 min. Plasma total digitoxin concentrations increased threefold during the hour after initial Fab infusion, while plasma free digitoxin concentration decreased to less than 0.1 ng/ml. Effects on digitoxin pharmacokinetics of these Fab fragments and the antibody population from which they were derived were further investigated in a primate species. Unlike common laboratory animals previously studied, the rhesus monkey was found to have a prolonged elimination half-life, estimated at 135 and 118 h by radioimmunoassay and [(3)H]digitoxin measurements, respectively, similar to man and thus providing a clinically relevant experimental model. Intravenous administration of 2 mol of specific Fab fragments per mole of digitoxin 6 h after 0.2 mg of digitoxin produced a rapid 4.3-fold increase in plasma total digitoxin concentration followed by a rapid fall (t((1/2)) 4 h) accompanied by a 14-fold enhancement of urinary digitoxin excretion over control values during the 6-h period after Fab was given. Analytical studies were consistent with increased excretion of native digitoxin rather than metabolites, and the glycoside was found in equilibrium dialysis studies to be excreted in the urine in Fab-bound form. Administration of 2 mol of specific antibody binding sites per mole of digitoxin as intact IgG caused a greater and more prolonged increase in plasma total digitoxin concentration, peaking 13-fold above control levels. In contrast to the effects of Fab, however, specific IgG reduced the rate of urinary digitoxin excretion substantially below control values. We conclude that Fab fragments of antibodies with high affinity for digitoxin are capable of rapid reversal of advanced, otherwise lethal digitoxin toxicity, and are capable of reducing the plasma half-life and accelerating urinary excretion of digitoxin.
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PMID:Reversal of advanced digitoxin toxicity and modification of pharmacokinetics by specific antibodies and Fab fragments. 91 99

The blood levels of 25-hydroxyvitamin D (25-HCC) in 26 patients with nephrotic syndrome (proteinuria of 6.5 g/24 h +/- 0.8 SEM) ranged between 1 and 18.6 ng/ml (8.6 +/- 1.0 SEM). This value was significantly lower (P less than 0.01) than that in normal subjects (21.8 +/- 2.3 ng/ml) and patients with chronic renal failure (24.8 +/- 2.3 ng/ml). There was inverse correlation (P less than 0.01) between levels of 25-HCC and magnitude of proteinuria and a direct relation (P less than 0.01) with serum albumin. Reduction in proteinuria was rapidly followed by a rise in blood 25-HCC toward normal. Ionized calcium levels were low in 16 of 26 nephrotic patients irrespective of degree of renal failure. In four of seven nephrotic patients with normal renal function, ionized calcium levels were low and showed an inverse relation with levels of parathyroid hormone. These data show that patients with nephrotic syndrome have low blood levels of 25-HCC probably due to its loss in urine. This derangement is probably responsible for the disorders of calcium metabolism in nephrosis.
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PMID:Blood levels of 25-hydroxyvitamin D in nephrotic syndrome. Studies in 26 patients. 93 Dec 2

The EEG response and drug kinetics after intravenous infusion of diazepam at 1-0 mg/min until nystagmus, dysarthria, and moderate sedation developed, has been investigated in five normal subjects and 17 patients with chronic liver disease. Diazepam induced adequate premedication with a similar clinical response in all subjects with no adverse reactions. Maximal response was during or within five minutes of infusion. The dose of diazepam required in liver chronic disease was 17-9 +/- 1-4 mg (M +/- SEM) compared with 27 +/- 5-4 mg in controls (p less than 0-01). Dose correlated significantly with serum albumin (p less than 0-05). Baseline mean dominant frequency (MDF) and slow wave index (SWI) significantly correlated with albumin (p less than 0-01). After diazepam, the MDF decreased and SWI increased. The change was greatest at the time of maximal clinical response. It was greater in liverdisease and was greatest in patients with previous hepaticencephalopathy. In spite of reduced dose requirements in liver disease, there was no significant difference in plasma concentration at the end of drug infusion...
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PMID:Intravenous administration of diazepam in patients with chronic liver disease. 101 18


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