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Biomedical subjects

J D Cook

Publications and source records attributed to J D Cook.

At least 19 recordsLinked to original sources
PubMed1999

Higher concentrations of serum transferrin receptor in children than in adults.

BACKGROUND: The serum transferrin receptor (TfR) concentration in adults is suggested to provide a sensitive measure of iron depletion and together with the serum ferritin concentration to indicate the entire range of iron status, from iron deficiency to iron overload. However, little is known about TfR concentrations in children. OBJECTIVE: Our objective was to compare serum TfR and ferritin concentrations and their ratios in children and adults and look for correlations between TfR concentrations and other measures of iron status. DESIGN: Our study groups were healthy 1-y-old infants (n = 36), 11-12-y-old prepubertal boys (n = 35), and 20-39-y-old men (n = 40). RESULTS: TfR concentrations were higher in infants (x; 95% reference interval: 7.8 mg/L; 4.5, 11.1) than in prepubertal boys (7.0 mg/L; 4.7, 9.2) and higher in prepubertal boys than in men (5.8 mg/L; 3.1, 8.5). Geometric mean TfR-ferritin ratios were higher in infants (316; 95% reference interval: 94, 1059) than in prepubertal boys (219; 78, 614) and higher in prepubertal boys than in men (72; 23, 223). By multiple linear regression analysis, the best predictors of TfR concentration were serum iron (P = 0.004) and log serum ferritin (P < 0.0001), both being inverse correlations (R2 = 0.32). Mean corpuscular volume, blood hemoglobin, transferrin iron saturation, transferrin, and even age seemed to not have an influence on the TfR concentration and erythropoiesis was not a determinant of TfR concentration. CONCLUSIONS: Low serum ferritin and iron concentrations, even within the normal physiologic range, result in high TfR concentrations. The lower the iron stores, the stronger the influence of ferritin on TfR. A high TfR concentration in children, especially in infants, is a response to physiologically low iron stores. Age-specific reference concentrations for TfR are needed.

Adult↗
PubMed1998

Management of hemochromatosis. Hemochromatosis Management Working Group.

The complications of iron overload in hemochromatosis can be avoided by early diagnosis and appropriate management. Therapeutic phlebotomy is used to remove excess iron and maintain low normal body iron stores, and it should be initiated in men with serum ferritin levels of 300 microg/L or more and in women with serum ferritin levels of 200 microg/L or more, regardless of the presence or absence of symptoms. Typically, therapeutic phlebotomy consists of 1) removal of 1 unit (450 to 500 mL) of blood weekly until the serum ferritin level is 10 to 20 microg/L and 2) maintenance of the serum ferritin level at 50 microg/L or less thereafter by periodic removal of blood. Hyperferritinemia attributable to iron overload is resolved by therapeutic phlebotomy. When applied before iron overload becomes severe, this treatment also prevents complications of iron overload, including hepatic cirrhosis, primary liver cancer, diabetes mellitus, hypogonadotrophic hypogonadism, joint disease, and cardiomyopathy. In patients with established iron overload disease, weakness, fatigue, increased hepatic enzyme concentrations, right upper quadrant pain, and hyperpigmentation are often substantially alleviated by therapeutic phlebotomy. Patients with liver disease, joint disease, diabetes mellitus and other endocrinopathic abnormalities, and cardiac abnormalities often require additional, specific management. Dietary management of hemochromatosis includes avoidance of medicinal iron, mineral supplements, excess vitamin C, and uncooked seafoods. This can reduce the rate of iron reaccumulation; reduce retention of nonferrous metals; and help reduce complications of liver disease, diabetes mellitus, and Vibrio infection. This comprehensive approach to the management of hemochromatosis can decrease the frequency and severity of iron overload, improve quality of life, and increase longevity.

Diet↗
PubMed1998

An assessment of dried blood-spot technology for identifying iron deficiency.

The present study was undertaken to assess the feasibility of using ferritin and transferrin receptor measurements on dried capillary blood spots to identify iron deficiency (ID) in public health surveys. Measurements on serum and blood spots prepared from venous blood were performed in 71 healthy subjects, 41 of whom were iron-replete and 30 who had ID, either without (n = 20) or with (n = 10) anemia. Parallel measurements were performed on hemolyzed whole blood and washed hemolyzed red blood cells to assess the erythrocyte contribution of ferritin and transferrin receptor to dried blood samples. The concentration of ferritin in dried blood samples was threefold higher than serum assays due to the release of ferritin from hemolyzed erythrocytes, which diminished the usefulness of ferritin measurements for detecting ID. On the other hand, there was negligible erythrocyte contribution to the measurement of transferrin receptor in dried blood spots. The most sensitive parameter in dried blood spots was the ratio of receptor/ferritin, which was suitable for identifying iron-deficiency anemia (IDA), but less reliable than serum assays for detecting milder ID without anemia. We conclude that tandem measurements of serum ferritin and transferrin receptor in dried blood spots can be used to facilitate the identification of IDA in epidemiologic studies.

Adult↗
PubMed1998

A comparison of iron absorption in adults and infants consuming identical infant formulas.

Fe absorption was estimated in adults and infants from the erythrocyte incorporation of Fe isotopes added to infant formula. Fe absorption was measured in adults using radioisotopes, and in infants with a stable-isotope technique. In adults, the geometric mean Fe absorption from a ready-to-feed soya formula with its native phytic acid content was 2.4%. This increased to 6.0% (P < 0.05) after almost complete dephytinization. In infants, mean Fe absorption values were 3.9 and 8.7% respectively from the same products (P < 0.05). In adults, mean Fe absorption from a spray-dried soya formula containing 110 mg ascorbic acid/l was 4.1%, increasing to 5.3% (P < 0.05) when ascorbic acid was doubled to 220 mg/l. In infants, mean Fe absorption values were 5.7 and 9.5% (P < 0.05) from the same products. Mean Fe absorption from a milk-based formula was 6.5% in adults compared with 6.7% in infants. All meals in the adult and infant studies were fed using an identical meal size of 217 g. Increasing the meal size threefold in adults did not change fractional Fe absorption. Mean Fe absorption values for each meal were lower in adults than in infants but the relative inhibitory effect of phytic acid and the enhancing effect of ascorbic acid were similar. We conclude that Fe absorption studies in adults can be used to assess the influence of enhancers and inhibitors of Fe absorption in infant formulas fed to infants. Further studies, however, are required to extend these findings to weaning foods and complete meals.

Adult↗
PubMed1997

Delivery of liposome-sequestered hydrophobic proteins to lysosomes of normal and Batten disease cells.

We have developed a method to deliver hydrophobic proteins such as ATP synthase subunit c and ubiquitin to lysosomes of PMN (polymorphonucleocytes) and fibroblasts. ATP synthase subunit c is stored in the lysosomes of various tissues in late infantile and juvenile forms of neuronal ceriod lipofuscinosis, also called Batten disease (BD). Whether this protein storage is due to an abbreviation in protein or in the lysosomal hydrolases of BD is still not clear. We have sequestered this protein and ubiquitin in the lipid membrane of liposomes. The liposomes coated with autologous heat-aggregated IgG or apolipoprotein E when presented to the PMN and fibroblasts, respectively, accumulated in the lysosomes. Both normal and BD PMN degraded 125I-ubiquitin; the rate of degradation was, however, slower by Batten PMN. These studies indicate that a hydrophobic molecule such as subunit c can be delivered to PMN and fibroblasts, and the sequestered proteins are accessible to lysosomal hydrolases. Therefore, this technique can be used to study the metabolism of highly hydrophobic proteins by lysosomes, especially the biochemical mechanism(s) of subunit c storage in BD.

Apolipoproteins E↗
PubMed1997

Body iron stores in relation to growth and pubertal maturation in healthy boys.

During male puberty, erythropoiesis is exceptionally active. Pubertal development and iron status were followed in 60 healthy boys at 3-month intervals for 24 months to evaluate changes in body iron stores with the serum transferrin receptor-ferritin ratio. The estimated amount of stored iron declined by about 50% over a 2-year period. Remarkable changes in iron stores were found even after as short an interval as 3 months and pubertal development was closely linked with a decrease in stored iron. The annual increments of estimated red blood cell (RBC) iron showed strong positive correlations with velocities in testicular volume and certainly in body height and weight. In contrast, the estimated changes in individual iron stores were not associated with any of those parameters. The lacking associations between iron stores and growth parameters are probably indicative of increasing intestinal absorption. Despite the relatively small quantitative role of iron stores in supplying iron for growth, falling iron stores probably play a more important regulatory role by stimulating iron absorption.

Adolescent↗
PubMed1997

Bovine ferritin iron bioavailability in man.

The bioavailability of ferritin iron was evaluated in human subjects using radiolabelled [55Fe]ferritin isolated from bovine spleen and liver. Preliminary studies with bovine spleen ferritin labelled in vitro demonstrated an inappropriately high absorption compared with ferritin labelled in vivo, and the latter was therefore used in all subsequent absorption studies. In 10 subjects, geometric mean absorption from 5 mg of ferritin iron was 3.8% when taken without and 3.2% when taken with food (P > 0.05). These values were significantly lower than absorption from the same dose of iron given as ferrous sulphate, which averaged 24.1% without and 8.2% with food. When the iron dose was increased 10-fold, absorption of ferritin iron averaged only 0.6-0.7% with or without food as compared with 7.9% without and 2.6% with food when the iron was given as ferrous sulphate. In a further study, mean absorption from bovine spleen ferritin of 4.0% did not differ significantly from the mean of 2.7% observed with bovine liver ferritin. These findings confirm previous studies indicating that ferritin iron is poorly absorbed. Furthermore, its use as a pharmaceutical iron preparation cannot be advocated.

Adult↗
PubMed1997

The influence of different cereal grains on iron absorption from infant cereal foods.

Iron absorption from various cereal grains was evaluated in the present study to identify possible preferences for the preparation of infant weaning foods. In six separate studies, four radioiron absorption tests were performed in each of 57 volunteer subjects by using a sequential double-isotopic method. Serum ferritin concentration was used to adjust for the effect of differences in the iron status of subjects participating in separate studies. Identical commercial processing and test meal composition were used to evaluate iron absorption from 50 g cooked cereal prepared from rice, wheat, maize, oats, millet, and sweet or bitter quinoa. In an initial evaluation of cereals fortified with 2.5 mg Fe as FeSO4, geometric mean absorption values were uniformly < 1% for all cereals and were not significantly different. In subsequent studies, percentage iron absorption was enhanced by either eliminating the fortifying iron or adding 50 mg ascorbic acid to the test meal. The effect was similar for most of the cereals tested with a composite mean increase in absorption of 37% when fortifying iron was removed and 270% when ascorbic acid was added. There was a strong inverse correlation between iron absorption and the phytate content of different cereals. Except for a modestly lower absorption of iron from quinoa and a remarkably higher absorption from one lot of maize, we conclude that the type of cereal grain has little influence on iron bioavailability of infant cereals. On the other hand, modification in the milling and processing methods for cereal grains that reduce their content of phytic acid is likely to improve iron availability significantly.

Absorption↗
PubMed1997

Effect of calcium intake on nonheme-iron absorption from a complete diet.

Recent studies based on radioiron measurements from single meals have suggested that calcium has a strongly inhibitory influence on nonheme-iron absorption. In view of evidence that the importance of various dietary enhancers and inhibitors of absorption is greatly diminished when assessed by labeling a complete diet, the present study evaluated the effect of variations in calcium intake on total dietary nonheme-iron absorption. Nonheme-iron absorption was measured in 14 healthy volunteers during three periods in which the diet was freely chosen or modified to decrease or increase dietary calcium intake maximally. The diet was labeled during each 5-d period by including with each of the two main meals of the day a small bread roll tagged extrinsically with radioiron. Carefully maintained dietary records indicated that 69-78% of the daily iron intake was labeled by this method. The basal calcium intake of 684 mg/d varied from 280 to 1281 mg/d when calcium intake was reduced or increased, respectively. Geometric mean iron-absorption values of 5.01%, 4.71%, and 5.83% for the three dietary periods were not significantly different from one another. No significant relation was observed between nonheme-iron absorption and dietary factors known to influence iron absorption. We conclude that calcium intake had no significant influence on nonheme-iron absorption from a varied diet.

Absorption↗
PubMed1997

Iron status of children with short stature during accelerated growth due to growth hormone treatment.

We determined the influence of human growth hormone (hGH) treatment on blood soluble transferrin receptor (sTfR) in 35 children with short stature. Whereas the serum concentration of ferritin decreased from 29.6 micrograms/l to 19.7 micrograms/l, and that of transferrin increased from 2.9 g/l to 3.2 g/l during 6 months (p < 0.001), only a minimum rise in the sTfR concentration was observed (7.12 +/- 0.20 mg/l vs 7.51 +/- 0.19 mg/l, p = 0.025). The prevalence of anaemia or microcytosis did not increase. Most of the changes in serum ferritin and transferrin concentrations occurred during the first week. The study demonstrates that rapid body growth per se does not affect the sTfR concentration, but it may affect the serum transferrin and ferritin concentrations. Alternatively, GH may have a specific effect on serum ferritin and transferrin concentrations.

Body Constitution↗
PubMed1997

Body iron stores decrease in boys during pubertal development: the transferrin receptor-ferritin ratio as an indicator of iron status.

The transferrin receptor in serum provides a useful measure of tissue iron deficiency and the rate of erythropoiesis, whereas serum ferritin reflects the amount of storage iron in normal subjects. We studied the serum transferrin receptor and the transferrin receptor-ferritin ratio in 57 healthy prepubertal or early pubertal boys and followed them at 3-mo intervals for 24 mo to evaluate their iron status during puberty. The mean laboratory parameters changed as follows: Hb from 13.0 to 13.3 g/dL (p = 0.01), mean corpuscular volume from 85 to 84 fL (p = 0.0001), transferrin receptor from 6900 to 7200 micrograms/L (p = 0.03) ferritin from 36 to 23 micrograms/L (p = 0.0001), and transferrin receptor-ferritin ratio from 230 to 400 (p = 0.0001). At the start of the investigation, the serum transferrin receptor was elevated (> 9000 micrograms/l) or ferritin low (< = or 12 micrograms/L) in fewer than 2% of the boys. During the subsequent 2 y the proportion of boys with an elevated transferrin receptor or low ferritin value increased. The two parameters were simultaneously abnormal in none of the boys initially, but in about 3% of the boys 2 y later. The change in transferrin receptor-ferritin ratio was closely correlated with genital development. The proportion of elevated transferrin receptor-ferritin ratios increased 4.5-fold during the 2 y, indicating the high responsiveness of the ratio. At the end of the study, iron therapy was started to eliminate any iron deficiency. In response to the therapy, the mean transferrin receptor-ferritin ratio fell to 210 +/- 19, i.e. close to the level at the beginning of the study. The marked responses of the transferrin receptor and the receptor-ferritin ratio to iron therapy reflect the dependence of these parameters on iron status rather than on physiologic differences in the rate of erythropoiesis.

Adolescent↗
PubMed1997

International collaborative study to evaluate a recombinant L ferritin preparation as an International Standard.

A recombinant L ferritin preparation, lyophilized in ampoules and designated 94/572, was evaluated by 18 laboratories in 9 countries for its suitability as an International Standard (IS). The preparation was assayed in a wide range of in-house and commercial immunoassays against the 2nd IS for ferritin (of spleen origin; 80/578). The immunological reactivity of the recombinant material was similar to that of the 2nd IS for ferritin in the majority of assays and demonstrated adequate stability in accelerated degradation studies. On the basis of the results presented here, the WHO Expert Committee on Biological Standardization established 94/572 as the 3rd IS for ferritin, recombinant.

Automation↗
PubMed1996

The influence of different protein sources on phytate inhibition of nonheme-iron absorption in humans.

The inhibiting effect of phytate on nonheme-iron absorption from different protein sources was examined in human subjects using extrinsic radioiron labeling. A drink containing maltodextrose and corn oil was used as a control meal to which was added sufficient sodium phytate to provide 300 mg phytic acid and/or various protein sources. The proteins were selected to cover a broad range of effects on bioavailability and included egg white, meat, and phytate-free soy protein. When sodium phytate alone was added, there was a pronounced 83-90% reduction in mean absorption in separate studies with a composite average decline of 86%. Despite a wide range in absorption from meals containing the three protein sources, a remarkably similar relative inhibition was observed when sodium phytate was added. No significant difference in the inhibiting effect of phytate could be detected with additions ranging from the equivalent of 50-300 mg phytic acid to a meal containing egg white as the protein source. Our studies found no evidence that the inhibiting effect of phytate depends on the protein composition of the meal.

Absorption↗
PubMed1996

The Caco-2 cell culture system can be used as a model to study food iron availability.

To assess the usefulness of the Caco-2 cell culture system as a model to study the availability of dietary iron, preliminary experiments were performed to determine the optimal conditions for iron uptake and transport. Iron uptake of radioactive ferrous sulfate was optimal at pH 5.5 using a 2:1 molar ratio of ascorbic acid to iron and a 1-h incubation time. Under these experimental conditions, we studied the effect on iron uptake of adding supernatants from homogenates of different meat sources, soybean protein isolates, egg albumen and bovine serum albumin. Iron uptake was 6.3 +/- 1.7% from meat, which was significantly greater (P < 0.001) than the values of 1.2 +/- 0.3% from soybean protein, 1.3 +/- 0.3% from egg albumen and 0.8 +/- 0.1% from bovine serum albumin. Iron uptake was also significantly higher from digested meat samples than from undigested meat when the protein concentration was equalized. Measurements of iron uptake and protein concentration from fractions obtained after preparative isoelectric focusing of meat and soybean protein extracts showed two peaks of higher protein concentration and iron uptake in meat, apparently not found in soybean protein, that contained the factor(s) responsible for the higher iron uptake by the cells. In view of these observed similarities with iron absorption studies in humans, we conclude that the Caco-2 cell culture system is a useful in vitro model to study food iron availability.

Ascorbic Acid↗
PubMed1996

Current issues in iron deficiency.

This brief review of developments relating to iron deficiency during the past year covers three main areas: iron supplementation, the regulation of iron absorption, and the use of the serum transferrin receptor for the assessment of iron status. The intermittent administration of iron supplement once or twice weekly rather than daily has been advocated by international health agencies in recent years, but radioiron absorption studies in human subjects have failed to demonstrate any absorptive advantage of the intermittent schedule. The value of prophylactic iron supplementation in elderly blood donors was evaluated and shown to offer limited benefit in maintaining donation frequency. A recent model of the regulation of iron absorption involving erythropoietic and store regulators is discussed and a recent article indicating a potential non-hematopoietic effect of hematopoietic growth factors on iron absorption by the gastrointestinal mucosal cell is reviewed. A new measure of functional iron deficiency, namely the serum transferrin receptor, is discussed, with particular reference to its mechanism of production and its great value in distinguishing iron deficiency anemia from the anemia of chronic disease.

Anemia, Iron-Deficiency↗