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J D Cook

Publications and source records attributed to J D Cook.

At least 37 records · Page 2Linked to original sources
PubMed1990

Serum transferrin receptor is a truncated form of tissue receptor.

Recent studies have provided immunological evidence for the existence of transferrin receptor in human serum and have revealed that its concentration is a sensitive measure of erythropoiesis and iron deficiency. The present study was undertaken to establish the molecular identity of this immunoreactive component. Purification from human serum was accomplished by immunoaffinity chromatography using, as the ligand, monoclonal antitransferrin receptor antibody. The receptor preparation contained two major components with Mr of 75,000 and 85,000, which were identified as transferrin and transferrin receptor, respectively. The physicochemical and immunochemical properties of the 85,000 serum receptor were compared with those established for intact placental transferrin receptor. The serum receptor exhibited an apparent Mr = 85,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under non-reducing conditions, as compared with 190,000 for placental transferrin receptor. Upon reduction, the Mr of serum receptor was unaltered, whereas, the 190,000 placental receptor dimer decreased to the expected monomer value of 95,000. Amino-terminal amino acid sequence analysis revealed that residues 1-19 of serum receptor were identical to residues 101-119 of intact receptor. These findings provide physicochemical evidence for the existence of transferrin receptor in human serum, establish its molecular identity as a truncated form lacking the cytoplasmic and transmembrane domains (residues 1-100) of intact receptor, and demonstrate that it exists as a transferrin-receptor complex in serum.

Amino Acid Sequence↗
PubMed1990

Isolation and characterization of a transferrin binding protein from rat plasma.

A transferrin binding protein was isolated from normal rat placenta and from iron-deficient rat plasma using a human transferrin affinity column. The yield of the isolated pure protein from iron-deficient rat plasma was about 0.5 micrograms/ml plasma. The major protein had a molecular mass of 85 kDa and contained carbohydrate. Reduction with mercaptoethanol did not change the molecular mass of the plasma transferrin binding protein whereas the native placental transferrin receptor of 180 kDa was reduced to 90 kDa. The transferrin binding protein reacted with both monoclonal and polyclonal antibodies raised against rat transferrin receptor. Immunoblotting of both normal and iron deficient rat plasma showed that the transferrin binding protein had a molecular mass of 85 kDa. In vitro digestion of purified rat placental transferrin receptor and red blood cells with trypsin provided an identical peptide profile, suggesting that the transferrin binding protein in rat plasma is derived from proteolysis of the extracellular portion of the transferrin receptor of the erythroid tissues.

Animals↗
PubMed1990

Gastric delivery system for iron supplementation.

A gastric delivery system (GDS) for iron supplementation was evaluated. Radioisotopic studies in 9 volunteers demonstrated a three-fold higher absorption of GDS iron compared with ferrous sulphate elixir. A double-blind placebo controlled trial was done in 200 women to compare the gastrointestinal side-effects associated with 50 mg iron daily given either as GDS or conventional ferrous sulphate. The conventional preparation was associated with a significantly higher frequency of nausea and anorexia, whereas there were no significant differences in reported side-effects between subjects receiving GDS or placebo. A single GDS capsule daily provides the same amount of absorbed iron as conventional ferrous sulphate given three times daily, and does not produce gastrointestinal side-effects.

Administration, Oral↗
PubMed1990

Serum transferrin receptor: a quantitative measure of tissue iron deficiency.

This study was undertaken to evaluate the role of serum transferrin receptor measurements in the assessment of iron status. Repeated phlebotomies were performed in 14 normal volunteer subjects to obtain varying degrees of iron deficiency. Serial measurements of serum iron, total iron-binding capacity, mean cell volume (MCV), free erythrocyte protoporphyrin (FEP), red cell mean index, serum ferritin, and serum transferrin receptor were performed throughout the phlebotomy program. There was no change in receptor levels during the phase of storage iron depletion. When the serum ferritin level reached subnormal values there was an increase in serum receptor levels, which continued throughout the phlebotomy program. Functional iron deficiency was defined as a reduction in body iron beyond the point of depleted iron stores. The serum receptor level was a more sensitive and reliable guide to the degree of functional iron deficiency than either the FEP or MCV. Our studies indicate that the serum receptor measurement is of particular value in identifying mild iron deficiency of recent onset. The iron status of a population can be fully assessed by using serum ferritin as a measure of iron stores, serum receptor as a measure of mild tissue iron deficiency, and hemoglobin concentration as a measure of advanced iron deficiency.

Adult↗
PubMed1990

Adaptation in iron metabolism.

Humans can adapt successfully to a wide range of iron requirements and intakes. The lower limit of the adapted state is best defined by serum ferritin greater than or equal to 12 micrograms/L, because lower values indicate that iron stores are fully depleted. Successful adaptation is achieved by modifying the rate of gastrointestinal absorption according to body iron needs. Several dietary variables, including total intake, content of heme, and bioavailability of nonheme iron, determine the ceiling of the adaptive response when iron demands are high. With lesser demands the nature of the diet has a limited influence on body iron reserves, although there is some evidence that the adaptive response to variations in heme iron intake is less complete than the response to differences in nonheme bioavailability. How the intestinal mucosal cell achieves adaptation is one of the most important unsolved questions in iron metabolism.

Adaptation, Physiological↗
PubMed1990

Serum transferrin receptor as an index of iron absorption.

Recent studies indicate that serum transferrin receptor levels are a quantitative index of tissue receptor mass. To determine whether the latter plays a role in the regulation of iron absorption, we examined the relationship between serum receptor, serum ferritin and iron absorption in healthy subjects. Using radioisotopic techniques we measured absorption of inorganic iron in 174 subjects and dietary nonhaem iron in 60 subjects. With both forms of iron, the correlation with absorption was far lower for serum receptor than for serum ferritin and was no longer significant when subjects with depleted iron stores were excluded. These results indicate that in normal subjects the iron store is the main physiological determinant of iron absorption and that in the absence of iron deficiency, tissue receptor mass, reflected by serum transferrin receptor levels, has no discernible influence.

Adult↗
PubMed1990

Skewed X inactivation in a female MZ twin results in Duchenne muscular dystrophy.

One of female MZ twins presented with muscular dystrophy. Physical examination, creatine phosphokinase levels, and muscle biopsy were consistent with Duchenne muscular dystrophy (DMD). However, because of her sex she was diagnosed as having limb-girdle muscular dystrophy. With cDNA probes to the DMD gene, a gene deletion was detected in the twins and their mother. The de novo mutation which arose in the mother was shown by novel junction fragments generated by HindIII, PstI, or TaqI when probed with cDNA8. Additional evidence of a large gene deletion was given by novel SfiI junction fragments detected by probes p20, J-Bir, and J-66 on pulsed-field gel electrophoresis (PFGE). Immunoblot analysis of muscle from the affected twin showed dystrophin of normal size but of reduced amount. Immunofluorescent visualization of dystrophin revealed foci of dystrophin-positive fibers adjacent to foci of dystrophin-negative fibers. These data indicate that the affected twin is a manifesting carrier of an abnormal DMD gene, her myopathy being a direct result of underexpression of dystrophin. Cytogenetic analysis revealed normal karyotypes, eliminating the possibility of a translocation affecting DMD gene function. Both linkage analysis and DNA fingerprint analysis revealed that each twin has two different X chromosomes, eliminating the possibility of uniparental disomy as a mechanism for DMD expression. On the basis of methylation differences of the paternal and maternal X chromosomes in these MZ twins, we propose uneven lyonization (X chromosome inactivation) as the underlying mechanism for disease expression in the affected female.

Adult↗
PubMed1990

Accuracy and precision of methods for theophylline measurement in physicians' offices.

We tested the accuracy and precision of five theophylline methods intended for use in physicians' offices. The Syntex AccuLevel, Ames Seralyzer, and 3M Diagnostics TheoFAST methods were less reproducible (CVs 6.3% to 9.2%) than the Abbott Vision and Kodak DT-60 (CVs 2.2% to 3.3%). Caffeine interfered with the Vision, Seralyzer, and AccuLevel methods, and theobromine interfered with the Vision, Seralyzer, and TheoFAST methods. Only the DT-60 method was free from interference from any of the 24 compounds tested. Results by all methods correlated well with those by the HPLC comparison method (Clin Chem 1981;27:1931-3) and by the Abbott TDx method for assay of 100 serum (or, when appropriate, paired whole-blood) samples. The frequency of sample results differing from the comparison method by greater than 2.0 mg/L was as follows: TDx, 11%; Vision (serum), 12%; Vision (whole blood), 18%; DT-60, 14%; AccuLevel, 18%; Seralyzer, 25%; and TheoFAST, 31%. The Kodak DT-60 method was the most nearly accurate and precise among these physician's office methods. Some physician's office methods for theophylline analysis are not adequate to guide dosage adjustments.

Humans↗
PubMed1990

Benzalkonium interference with test methods for potassium and sodium.

Six automated instruments that measure sodium and potassium were tested for interference from two compounds used in catheters. Tridodecylmethylammonium heparin did not interfere with any of the methods. However, benzalkonium heparin falsely increased sodium measurement with the Kodak Ektachem, and falsely increased potassium measurements with three instruments (Beckman Astra, Baxter Paramax, and the Instrumentation Laboratory Monarch) in which ion-selective electrodes measure potassium in diluted serum. Three instruments in which ion-selective electrodes measure serum directly--Du Pont Dimension, Abbott Spectrum, and Kodak Ektachem--experienced no interference with potassium measurements. Interference of benzalkonium with potassium measurements may result from its interaction with the electrode membranes, which is accentuated in diluted serum.

Benzalkonium Compounds↗
PubMed1989

Food iron absorption in idiopathic hemochromatosis.

The relationship between iron status and food iron absorption was evaluated in 75 normal volunteers, 15 patients with idiopathic hemochromatosis, and 22 heterozygotes by using double extrinsic radioiron tags to label independently the nonheme and heme iron components of a hamburger meal. In normal subjects, absorption from each of these pools was inversely correlated with storage iron, as measured by the serum ferritin concentration. In patients with hemochromatosis, absorption of both forms of iron was far greater than would be predicted from the relationship between absorption and serum ferritin observed in normal volunteers. Nevertheless, there was still a modest but statistically significant reduction in absorption of nonheme iron with increasing serum ferritin. This relationship could not be demonstrated in the case of heme iron absorption. In heterozygotes, nonheme iron absorption from a hamburger meal containing no supplementary iron did not differ significantly from that observed in normal volunteers. However, when this meal was both modified to promote bioavailability and supplemented with iron, absorption of nonheme iron was significantly elevated. These studies confirm the presence of excessive nonheme iron absorption even from unfortified meals in patients with idiopathic hemochromatosis and suggest in addition that they are particularly susceptible to iron loading from diets containing a high proportion of heme iron. Impaired regulation of nonheme iron absorption was also observed in heterozygous individuals, but a statistically significant abnormality was demonstrable only when the test meal contained a large highly bioavailable iron supplement.

Adult↗
PubMed1989

Gastrostomy and Nissen fundoplication in neurologically impaired children.

We report our experience with 90 neurologically impaired children treated with gastrostomy and Nissen fundoplication. Malnutrition was the main problem, followed by aspiration, recurrent pneumonia, and vomiting. The symptomatology was caused by swallowing incoordination and gastroesophageal reflux. The diagnosis of gastroesophageal reflux was confirmed by upper gastrointestinal series and pH probe. Nissen fundoplication was performed following a standard technique with preservation of the vagus nerves and its branches, repair of the diaphragmatic crura, reconstruction of the angle of His, and a 360 degree wrap. A gastrostomy and pyloroplasty or pyloric dilatation were part of the operative procedure. There were no deaths and few complications related to the surgical procedure. Marked nutritional improvement was seen in most cases with an average weight gain of 3.2 kg/patient 3 months following surgery. There was also improvement in milestones and seizure control. The majority of parents were very satisfied and would recommend the procedure to other parents with similar problems.

Adolescent↗
PubMed1989

Comparison of in vitro, animal, and clinical determinations of iron bioavailability: International Nutritional Anemia Consultative Group Task Force report on iron bioavailability.

Relative bioavailability of two iron fortificants, electrolytic Fe and ferric orthophosphate, was related to that of the reference ferrous sulfate with in vitro and rat model depletion-repletion methods in four laboratories to compare values directly with those obtained in a parallel human study. In vitro testing was performed on Fe compounds with both solubility and dialysis in a simulated in vitro gastrointestinal digestion system. Two depletion-repletion techniques, hemoglobin-regeneration efficiency (HRE) and an official method of the Association of Official Analytical Chemists (AOAC), were examined. AOAC relative biological values (RBV) of electrolytic Fe were 0.66 and 0.78 and of FePO4 were 0.25 and 0.34. HRE values were 0.78 and 0.58 for electrolytic Fe and FePO4, respectively. When compared with FeSO4 in a radiolabeled farina-based meal fed to humans, the RBV of FePO4 was 0.25 and electrolytic Fe 0.75. Results obtained with the AOAC method serve as the most reliable prediction of Fe bioavailability in the human although in vitro dialysis is a promising screening technique.

Animals↗
PubMed1989

Iron absorption in humans as influenced by bovine milk proteins.

The effect of the two major bovine milk protein fractions on the dialyzability of iron in vitro under simulated gastrointestinal conditions and on the absorption of Fe by humans was studied. Liquid-formula meals were prepared from hydrolyzed maize starch, corn oil, and either spray-dried egg white or a milk-protein product. In meals containing egg white, 3.32% of the Fe was dialyzable. The substitution of casein and whey protein products reduced the dialyzable fraction to 0.19-0.56% and 0.86-1.60%, respectively. Percentage Fe absorption was also reduced by the substitution of casein or whey protein for egg white. Mean absorption values fell from 6.67 to 3.65% and 2.53 to 0.98%, respectively. When the intact milk-protein products were replaced by enzyme- or acid-hydrolyzed preparations, the dialyzable fraction increased markedly and in proportion to the extent of hydrolysis. A similar but much smaller effect on absorption was observed. These studies suggest that bovine casein and whey proteins are responsible at least in part for the poor bioavailability of the Fe in some infant formulas.

Adult↗