Gene/Protein Disease Symptom Drug Enzyme Compound
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To evaluate a pediatric trace element supplement (Ped-El, Pharmacia) 18 metabolic balance studies were completed in 13 infants (mean birth weight 909 +/- 67 g, x +/- SEM; mean gestational age 27.2 +/- 1 weeks) who received total parenteral nutrition. The supplement supplied 40 micrograms/kg/day of zinc resulting in negative retention of 226 micrograms/kg/day. Copper infused at 20 micrograms/kg/day led to a positive retention of 8 micrograms/kg/day and an increase in serum Cu (p less than 0.05) not related to Cu intakes. Manganese infused at 40 micrograms/kg/day was nearly all retained (88 +/- 16% retention). Iron infused at 120 micrograms/kg/day led to a positive retention of 93 micrograms/kg/day. Although plasma ferritin and percent transferrin saturation were elevated, only plasma Fe values were correlated with Fe intake. This trace element supplement does not appear suitable for very low birth weight preterm infants.
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PMID:Zinc, copper, manganese, and iron balance of parenterally fed very low birth weight preterm infants receiving a trace element supplement. 313 48

Nitrogen metabolism and plasma insulin level were studied postoperatively in 14 patients (six males and eight females) with a disease of the upper gastrointestinal tract and therefore operated on electively. The patients received one of the two isocaloric parenteral nutrition regimens postoperatively: one, on the average, with 1.2 g of amino acids/kg/day and the other with 3.1 g of amino acids/kg/day. During postoperative intravenous alimentation rich in amino acids the cumulative nitrogen balance over 3 days was +13.1 (interval from -1.3 to +21.4) gN but -10.1 (interval from -12.1 to -2.4) gN during parenteral nutrition with a smaller amount of amino acids. The difference was significant (p less than 0.001). During parenteral nutrition rich in amino acids the changes of the serum albumin level, ie, -0.4 (SEM 1.1) g/liter, and of the serum transferrin level, ie; -0.16 (SEM 0.22) g/liter, were statistically insignificant (p greater than 0.05). During intravenous alimentation poor in amino acids serum albumin decreased by 3.8 (SEM 1.2) g/liter (p less than 0.01) and serum transferrin by 0.44 (SEM 0.05) g/liter (p less than 0.001). The differences of the changes between the groups were significant (p less than 0.01 and p less than 0.01, respectively). These various effects of the two parenteral nutrition regimens were not dependent on the different fluid balances during intravenous alimentation or on the different plasma insulin levels. It is concluded that a rich supply of amino acids--more than 1.2 g/kg/day--in postoperative parenteral nutrition better maintains the visceral protein levels in the serum, which possibly depends on the greater protein production in the liver.
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PMID:Maintenance of visceral protein levels in serum during postoperative parenteral nutrition. 314 41

In patients with a nephrotic syndrome administration of prednisolone causes an increase of proteinuria. To elucidate the mechanism of this effect we have studied the acute proteinuric effect of prednisolone, 125 to 150 mg intravenously, in nine patients (7 M, 2F) with a nephrotic syndrome. Mean age (+/- SD) of the patients was 53 +/- 6 years, mean endogenous creatinine clearance 104 +/- 30 ml/min, and mean proteinuria 7.7 +/- 3.0 g/24 hr. After administration of prednisolone, urinary total protein excretion rose in all patients from a mean (+/- SEM) of 4.89 +/- 0.59 mg/min before to 9.09 +/- 0.99 mg/min at five hours after administration (P less than 0.01). Glomerular filtration rate (inulin clearance), effective renal plasma flow (PAH clearance), and filtration fraction did not change significantly. The increases of urinary excretion of albumin (median %: +92%), IgG (median %: +88%), and transferrin (median %: +76%) were comparable and correlated significantly. Urinary excretion of beta 2-microglobulin did not change significantly however. We conclude that intravenous administration of prednisolone to patients with a nephrotic syndrome causes an increase in urinary protein excretion rate which cannot be explained by changes in renal hemodynamics or tubular protein reabsorption, and which therefore must be the result of a change in glomerular permselectivity characteristics.
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PMID:Prednisolone can increase glomerular permeability to proteins in nephrotic syndrome. 340 15

Hypothesizing that any effect of an increased serum iron and transferrin saturation on the risk of bacterial infection would be particularly important in immunosuppressed patients, we reexamined the effect of hyperferremia on bacterial growth in vitro and studied the pattern and prevalence of hyperferremia in patients receiving treatment for acute nonlymphocytic leukemia (ANLL). Growth of inocula of Escherichia coli and Staphylococcus aureus was significantly greater (1.3- to 5.8-fold) in fresh or heat-inactivated sera obtained from 10 healthy volunteers 3 hours after oral ingestion of ferrous sulfate (mean +/- SEM transferrin saturation 95% +/- 3%) than before (transferrin saturation 34% +/- 10%). Similarly, in heat-inactivated serum samples obtained from six patients with various malignancies, growth of E. coli was significantly greater (2.3- to 5.5-fold) with the elevated transferrin saturation (97% +/- 3%) present 1 to 7 days after receiving chemotherapy than with the normal transferrin saturation (33% +/- 9%) present before. In a prospective evaluation of serial serum iron studies in 12 patients receiving treatment for ANLL, five patients had normal serum iron concentrations initially, but in each patient the transferrin saturation was elevated after receiving chemotherapy, usually to greater than 90% for greater than 15 days in conjunction with prolonged, profound granulocytopenia and fever.
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PMID:Hyperferremia in immunosuppressed patients with acute nonlymphocytic leukemia and the risk of infection. 353 24

We examined the hypothesis that increased pulmonary transvascular protein flux after cardiopulmonary bypass (CPB) is mediated in part by neutrophil-derived, oxygen-free radicals. Measurements of transvascular lung 113mIn-transferrin flux, transpulmonary neutrophil counts, and plasma concentrations of thiobarbituric acid (TBA) reactive substances were made in 8 dogs after CPB and in 6 dogs who underwent thoracotomy alone. The TBA reactivity is indicative of lipid peroxidation and was used as an index of oxygen-free radical release. All 14 dogs had a baseline measurement of lung protein flux 1 wk prior to thoracotomy. In the bypass dogs, lung protein flux was -0.2 +/- 0.3 protein flux units (mean +/- SEM) at baseline and increased significantly after bypass to 3.3 +/- 1.0 (p less than 0.01). The control thoracotomy group had baseline values similar to the baseline studies in the CPB dogs (0.2 +/- 0.3 units), but no significant difference was noted after thoracotomy. The CPB dogs showed initial significant parallel falls in left atrial (LA) and central venous (CV) neutrophil counts during bypass (baseline, 5.3 +/- 0.7 X 10(9) cells/L in both sample sites, falling to 3.0 +/- 0.5 and 2.9 +/- 0.5, respectively, p less than 0.001), but a significant CV-LA transpulmonary gradient existed only when pulmonary perfusion recommenced after a period of total asystole. Concentration of TBA reactive substances increased significantly during the course of bypass (baseline LA, 6.4 +/- 0.5 nmol/L, baseline CV, 6.4 +/- 0.5, increasing to 9.8 +/- 1.0 and 9.4 +/- 1.6 at the end of bypass, respectively, p less than 0.01), but likewise, there was a significant transpulmonary gradient only after reversal of asystole.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased pulmonary transvascular protein flux after canine cardiopulmonary bypass. Association with lung neutrophil sequestration and tissue peroxidation. 377 83

Chronic inflammation in such diseases as rheumatoid arthritis has been associated with the accumulation of iron in mononuclear phagocytes. Cigarette smoking, which also produces chronic pulmonary inflammation, may be associated with iron accumulation in alveolar macrophages (AM). We have examined the total iron content in human AM and found it to be 43.0 +/- 7.7 (mean +/- SEM) and 12.8 +/- 1.3 nmol/1 X 10(6) cells (P less than 0.01) from smokers and nonsmokers, respectively. Because the higher iron content in smokers' macrophages may reflect increased internalization, the binding and uptake of iron-saturated transferrin was examined in cells from smokers and nonsmokers. However, no significant differences were found between the two groups. The smoking-related alteration in iron content may instead reflect differences in the fate of internalized iron. Iron internalized by AM as iron 59 initially bound to transferrin was distributed to a cytoplasmic, largely ferritin-associated, pool more slowly in smokers than in nonsmokers, during a 24-hour incubation in vitro. Significantly less newly internalized iron was returned to the culture medium by AM from smokers, which by 24 hours had released 11.0% +/- 3.7% of the initially internalized 59Fe compared with 36.0% +/- 2.3% for nonsmokers (P less than 0.01). The increased accumulation of iron by AM in the alveolar space of smokers may modulate hydroxyl radical production in the microenvironment of these cells.
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PMID:Iron binding, internalization, and fate in human alveolar macrophages. 378 29

Serum was collected from children with type 1 diabetes mellitus before and 10 days after attending a camp session in which blood glucose concentrations were carefully controlled. Glycosylated and nonglycosylated proteins were separated, and levels of albumin and transferrin were determined on each of these fractions. Glycosylated hemoglobin was also determined and ranged from 4.6% to 14.6% (mean +/- SEM 8.1% +/- 0.2%). Mean initial glycosylated albumin in 73 children was 16.4% +/- 0.6%, which was elevated compared with the mean of levels in 20 nondiabetic controls (8.7% +/- 0.3%) and correlated well with levels of glycosylated hemoglobin (r = 0.71). After 10 days mean glycosylated albumin fell to 14.6% +/- 0.5% (P less than 0.00001), near the predicted final value of 13.4% if control had been ideal. Initial levels of glycosylated transferrin in 44 of these children ranged from 4.5% to 22.3% (11.4 +/- 0.6%) and was significantly higher than the mean of 3.8% +/- 0.3% in 20 nondiabetic controls. Mean final glycosylated transferrin fell to 8.2% +/- 0.3% (P less than 0.00001), near the predicted final mean of 7.0% +/- 0.2%. The mean of each subject's blood glucose determinations performed throughout the study period correlated with final levels of both glycosylated albumin (r = 0.55, P less than 0.001) and glycosylated transferrin (r = 0.54, P less than 0.001). Both glycosylated albumin and glycosylated transferrin appear to be reliable markers of short-term glycemic control; glycosylated transferrin (half-life 8 days) was more sensitive than glycosylated albumin over this 10-day period.
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PMID:Glycosylated albumin and transferrin: short-term markers of blood glucose control. 647 Aug 61

We have examined the secretion and binding of transferrin to rat testicular cells. The only testicular cells found to secrete transferrin were the Sertoli cells (control 549 +/- 6; FSH 1020 +/- 17 ng/day X 10(6) cells, mean +/- SEM). The Sertoli cells also contained specific binding sites for transferrin with a Kd of 2.0 X 10(-9)M. Of the other testicular cells examined only fractions rich in pachytene spermatocytes possessed specific transferrin-binding sites. Late pachytene spermatocytes (97% pure) bound [125I]iodotransferrin with a similar affinity as Sertoli cells (Kd 1.7 X 10(-9)M). Fractions of early and mid pachytene spermatocytes contained transferrin-binding sites with a higher affinity (Kd 0.3 X 10(-9)M). This is the first report of a protein that has specific binding sites on germ cells.
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PMID:Transferrin binds specifically to pachytene spermatocytes. 662 33

Sulfation and thymidine activities were measured in 14 insulin-treated diabetic children aged 4 to 16 years. Mean plasma sulfation activity was 0.86 +/- SEM 0.09 U/ml, values being highly significantly negatively correlated with Hb A1c (r = 0.663, p less than 0.01) and with 24 hours glucosuria (r = 0.764, p less than 0.001). Mean plasma thymidine activity was 1.04 +/- SEM 0.09 U/ml) but not with the other parameters. No relationship was found between sulfation and thymidine activities and insulin concentrations in the same samples. Additionally mean plasma transferrin concentration was 2.732 +/- SEM 0.152 U/ml, not significantly different from normal values. These data demonstrate that, in diabetic children treated by insulin, sulfation factor level is closely correlated to the quality of the control of the metabolic disorder. In contrast, thymidine activity of plasma appears to be unaffected by the level of glycemic regulation.
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PMID:[Plasma sulfation and thymidine activities in diabetic children and adolescents]. 676 76

Serum zinc concentrations and urine zinc excretion have been studied in 10 patients with severe Crohn's disease before and during 59 patient-weeks of intravenous nutrition. Before serum zinc concentrations (9.9 +/- 1.0 mumol/l: mean +/- SEM) and urine zinc excretion (3-3 +/- 0.6 mumol/24h) were less than controls (p less than 0.01). No patients had clinical signs of zinc deficiency before intravenous nutrition and none developed signs during it. There was no overall change in serum zinc concentrations, despite improvements in body weight, skinfold thickness, and mid-arm circumference in all patients, and increased serum albumin and serum transferrin concentrations during all but two periods of intravenous nutrition. Nor was there any relationship between serum zinc concentrations and zinc uptake (up to 220 mumol/day), serum zinc concentrations remaining significantly lower than control levels. Urine zinc excretion during the first week of intravenous nutrition showed a 1.2 to 53-fold increase (mean 11-fold) over pre-intravenous nutrition levels, and a positive relationship was demonstrated between zinc intake and urine zinc excretion. It is suggested that zinc supplied by the intravenous route is inefficiently transported to the tissues, and that some is excreted in the form of small molecular weight chelates into urine. Recommendations are made for the supply of intravenous zinc, based on monitoring urine zinc excretion in individual patients.
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PMID:Clinical experience of zinc supplementation during intravenous nutrition in Crohn's disease: value of serum and urine zinc measurements. 681


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