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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

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

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

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

The use of continuous quality improvement to achieve proper isolation of patients with suspected tuberculosis.

The infection control staff worked on their first project that used the methods of continuous quality improvement from January through July 1993. The purpose of this initial project was to achieve proper isolation of patients with suspected tuberculosis. Flowcharting revealed that appropriate clinical performance by the charge nurses was crucial, and cause and effect diagraming demonstrated the importance of good policies and procedures. The team hypothesized that the charge nurses' current knowledge of tuberculosis and isolation procedures was low and that fewer exposures would occur if a concerted effort were made to educate this particular group. A self-administered examination to test their knowledge base was completed by 87% of approximately 75 charge nurses. The average score was 48 of a possible score of 100. Eight education programs were given to the charge nurses; these included information about tuberculosis and revised policies and procedures. After the intervention, the test was readministered to a group of 20 charge nurses. Scores of this group improved by 49%. Mistakes were made and lessons were learned in this first continuous quality improvement endeavor. Despite the flaws in this project, its ultimate goal of reducing exposures to tuberculosis was achieved.

Algorithms

ATP synthase subunit C storage in the polymorphonucleocytes of late infantile and juvenile batten patients.

In late infantile and juvenile forms of neuronal ceroid lipofuscinosis, commonly known as Batten disease (BD). ATP synthase subunit c accumulates in the lysosomes of neural cells. By using polyclonal antibodies, raised against bovine liver subunit c and an image analysis system for the quantification of antibody-linked alkaline phosphatase reaction, we have demonstrated that polymorphonucleocytes (PMN) from a late infantile and a juvenile BD patient stored several-fold more subunit c as compared to normal PMN.

Age of Onset

The effect of red and white wines on nonheme-iron absorption in humans.

The effect of the phenolic compounds in wine was examined in this study by performing radioiron-absorption measurements from extrinsically labeled test meals in 33 human subjects. In four separate studies we observed that absorption was 2- to 3-fold higher from white wine containing a low concentration of polyphenols than from two red wines containing a 10-fold higher concentration of polyphenols. The interaction between the polyphenols and alcohol in wine was evaluated by reducing the alcohol content of the wines by approximately 90%. When the alcohol concentration was reduced, there was a significant 28% decrease in nonheme-iron absorption with red wine but no effect with white wine. The inhibitory effect of red wines with reduced alcohol content was about twofold greater when they were consumed with a small bread roll than when taken without food. Our findings indicate that the inhibitory effect of phenolic compounds in red wine is unlikely to affect iron balance significantly.

Adult

Efficacy of weekly compared with daily iron supplementation.

A reduction in the frequency of iron supplement administration to once or twice weekly is being widely examined in developing countries on the assumption that the side effects of oral iron will decrease and that the reduction in administered iron will be offset by a lesser inhibition in absorption from iron taken on the previous day. We examined this premise by measuring iron absorption from 50 mg radiolabeled ferrous sulfate in 23 female volunteer subjects divided into two groups. In the first group, a labeled ferrous sulfate supplement was given with water, and in the second group it was given with a rice-based meal. In both groups, absorption was measured in a randomized fashion twice in each subject, once with daily and once with weekly supplementation. Those tested for daily supplementation were given an iron supplement daily for 6 d before testing whereas those tested for weekly supplementation were given no iron for 6 d before testing. When the labeled iron supplement was given with water only, absorption averaged 8.5% with daily and 9.8% with weekly administration compared with 2.3% and 2.6%, respectively, when given with food. The 13% lower absorption observed with daily administration in both groups was not statistically significant (P > 0.20). These results indicate that there is no significant absorptive advantage in giving iron less often than once daily.

Adult

Interleukin-11 enhances gastrointestinal absorption of iron in rats.

The effect of parenteral administration of IL-11 on gastrointestinal iron absorption was evaluated. A significant increase in the absorption of 59Fe-tagged food iron fed to fasting rats was observed when two subcutaneous injections of IL-11 were given 48 and 24 h prior to testing. Relatively similar increases of 25% were observed with IL-11 doses of 300, 600 and 1000 micrograms/kg for each injection. The increase in absorption did not appear to be related to changes in erythropoiesis. These findings raise the possibility that the enhanced absorption of iron which occurs with ineffective erythropoiesis may in part be mediated by multifunctional haemopoietic growth factors.

Animals

Ferritin excretion and iron balance in humans.

Under normal circumstances, most of the lumenal iron taken into the intestinal mucosal cell is stored within the cell as ferritin and subsequently is lost in the faeces when the cell exfoliates at the end of its lifespan. To evaluate whether faecal iron proteins reflect mucosal cell iron as well as whole body iron and to examine further the kinetics of gastrointestinal iron transport, faecal H-rich and L-rich ferritin were measured in normal subjects and patients with iron deficiency and genetic haemochromatosis. In normal and iron-deficient subjects, the concentration of L-rich but not H-rich faecal ferritin correlated closely with body iron status. In genetic haemochromatosis, the faecal L-rich and H-rich ferritin concentrations were lower than expected for their body iron status. The administration of oral iron to normal subjects led to a rise in L-rich ferritin. Administration of oral or parenteral iron to patients with iron deficiency led to a prompt rise in both forms of faecal ferritin, although the relative increase of L-rich ferritin was greater than that of H-rich ferritin with oral iron administration. Faecal ferritin correlated closely with iron stores in normals and patients with iron deficiency but faecal ferritin levels were lower than expected in genetic haemochromatosis, similar to that previously noted in the duodenal mucosal cells of these patients.

Administration, Oral

Serum transferrin receptor in hereditary hemochromatosis and African siderosis.

The present investigation evaluated the serum transferrin receptor concentration in subjects with nontransfusional iron overload who were identified in two separate studies on the basis of a serum ferritin level above 400 micrograms/L. Subjects with preclinical hereditary hemochromatosis were evaluated in the first study and those with the African form of iron overload in the second. In the first study, hereditary hemochromatosis was identified in 14 white men on the basis of a persistent elevation in transferrin saturation above 55%. The serum receptor concentration was elevated above the upper cut-off of 8.5 mg/L in two of the subjects, but the mean receptor of 6.1 +/- 1.4 mg/L (mean +/- 2 SE) did not differ significantly from the normal mean for this assay of 5.6 +/- 0.3 mg/L. In the same study, 60 control subjects with secondary iron overload were identified on the basis of a serum ferritin persistently above 400 micrograms/L, with a normal serum C-reactive protein concentration but with a transferrin saturation < 55%. Three of these subjects had an elevated serum receptor concentration but the mean value of 5.5 +/- 0.4 mg/L did not differ from normals nor from subjects with hemochromatosis. In the second study, 49 black Africans with iron overload were divided into those with or without an elevated transferrin saturation. The mean serum receptor concentration of 5.0 +/- 0.8 mg/L and 4.5 +/- 0.4 mg/L, respectively, did not differ statistically. It was concluded that there is no evidence of generalized dysregulation of the transferrin receptor in hemochromatosis or African siderosis.

Adult

Transient mutism following posterior fossa surgery in children.

We report 3 patients, ages 5, 9 and 13 years, with mutism following posterior fossa surgery (PFS). All presented with headache of 10-180 days duration, excellent premorbid learning performance and paucity of neurologic signs. Radiographic studies demonstrated large posterior fossa tumor occupying the fourth ventricle, and hydrocephalus, leading to gross total resection of the tumor. Within 24-48 hr, all patients were mute. None had problems with swallowing and coughing. All were able to nod "yes or no," follow commands, point to body parts, and make their wants known by gestures. Jaw, gag, snout and palmomental reflexes were normal. CT scan and MRI Brain showed no cerebral hemispheric lesions. All children regained speech although dysarthric, within 5-12 weeks. Twenty-two previously reported cases are similar to ours. We conclude that this post-surgical mutism syndrome is unique and must be differentiated from aphemia, Broca's aphasia, hysterical mutism and elective mutism. The cerebellum, in a way not yet understood, does play a role in speech production.

Adolescent

Iron deficiency: the global perspective.

The prevelance of IDA in industrialized countries has declined in recent decades, but there has been little change in the worldwide prevalence. IDA is currently estimated to affect more than 500 million people. Recent studies have indicated that anemia per se, the most common manifestation of iron deficiency, is less important from a public health standpoint than liabilities associated with tissue iron deficiency. The most important of the latter are an impairment in psychomotor development and cognitive function in infants and preschoolers, a deficit in work performance in adults, and an increase in the frequency of low birth weight, prematurity, and perinatal mortality in pregnancy. There have been several recent advances in combatting nutritional iron deficiency. One of the major problems has been in distinguishing iron deficiency from other causes of anemia seen epidemiologically such as malaria, HIV infection, chronic inflammation, hemoglobinopathies, and protein energy malnutrition. When combined with serum ferritin and hemoglobin determinations, the serum transferrin receptor assay is a valuable addition in epidemiologic surveys because it provides a quantitative measure of functional iron deficiency and it distinguishes true IDA from the anemia of chronic disease. The most difficult challenge is to develop effective methods of supplying iron to large segments of a population. Supplementation with iron tablets is suitable for only brief periods of need such as during pregnancy. The poor compliance with existing supplementation programs is believed to be due mainly to the gastrointestinal side effects of oral iron which can be eliminated by the use of a gastric delivery system. The most effective long-term strategy is to increase the intake of bioavailable iron in the diet. The customary approach has been to fortify a food staple such as wheat, rice, sugar, or salt, and thereby increase the iron intake of the entire population. However, because of concerns about the risk of cancer and heart disease in individuals with high iron stores, there is an increasing reluctance to supply iron to individuals who do not require it. A more effective strategy is to fortify food vehicles that are targeted to segments of the population at greatest risk of iron deficiency such as infants and school children. Because of the strong inhibitory properties of diets in regions of the world where iron deficiency is most prevalent, the use of NaFeEDTA has important advantages for food fortification.

Anemia, Iron-Deficiency

The physiological significance of circulating transferrin receptors.

A soluble truncated form of the tissue transferrin receptor has been recently identified in human serum. The concentration of this serum receptor appears to reflect the total mass of tissue receptor and is consequently elevated with tissue iron deficiency and enhanced red cell production. When coupled with the serum ferritin, the serum transferrin receptor concentration provides a sensitive, quantitative index of iron status over a wide spectrum. While the physiological significance of the circulating receptor is still unknown, this new laboratory measurement will play an important role in the clinical and epidemiological detection of iron deficiency anemia.

Erythropoiesis

Iron-deficiency anaemia.

Iron-deficiency anaemia (IDA) is a common clinical problem throughout the world and an enormous public health problem in developing countries. The cornerstone of the laboratory identification of IDA is a low haemoglobin and serum ferritin concentration although a normal serum ferritin does exclude IDA. When the serum ferritin is normal in an anaemic patient with iron-deficient erythropoiesis, it is common practise to perform a bone marrow examination to diagnose IDA. The recent introduction of serum transferrin receptor measurements is a useful alternative for distinguishing IDA from the anaemia of chronic disease because the serum receptor concentration is usually elevated in patients with IDA but normal in patients with anaemia due to inflammation or neoplasia. It is helpful for the clinican to be aware of the causes of physiological IDA. The most important are increased rate of body growth, excessive menstrual blood loss, pregnancy, regular blood donation, intensive endurance training, chronic aspirin use and a vegetarian diet. Without these, a careful search for unsuspected gastrointestinal blood loss must be made and even when the suspicion of physiological IDA is high, it is prudent to screen for fecal occult blood. In most patients, IDA responds promptly to oral iron therapy. Patients who experience troublesome side-effects with oral iron might benefit from a gastric delivery system for oral iron which eliminates nausea and vomiting and improves iron absorption when given with food.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Inhibitory effect of a soybean-protein--related moiety on iron absorption in humans.

The inhibitory effect of soybean protein isolates on nonheme-iron absorption was studied in 34 human subjects. Iron absorption was measured by using an extrinsic radioiron label in liquid-formula meals containing hydrolyzed corn starch, corn oil, and either egg white or a series of soybean-protein derivatives. The unmodified soybean-protein isolate markedly inhibited iron absorption. Percentage absorption was 19-fold higher when an extensively enzyme-hydrolyzed preparation with very little phytate was used as the protein source. Both the glycinin (11S) and conglycinin (7S) fractions of soybean protein were inhibitory to iron absorption. Dephytinization removed the inhibitory effect of the glycinin but not of the conglycinin fraction. We conclude that there are two major inhibitors of iron absorption in soybean-protein isolates, phytic acid and a protein-related moiety contained in the conglycinin (7S) fraction.

Absorption

Absorption of nonheme iron in ascorbic acid-deficient rats.

Prior studies have shown that the absorption of dietary nonheme iron in rats is much higher and less responsive to dietary variables than in human subjects. The aim of the present study was to determine whether this dissimilarity is explained by species differences in ascorbic acid status or metabolism. Iron absorption studies were performed with normal rats and with a genetic strain that lacks the ability to synthesize the vitamin. Ascorbic acid deficiency was produced in these animals by removing supplemental vitamin C from the diet for a brief period before the study. Iron absorption was measured from meals tagged extrinsically with 59Fe and measured by whole-body counting. We studied the effect on iron absorption of adding meat, ascorbic acid, soybean, tea, or bran to the test meal. A significant but modest effect of bran on iron absorption was observed in normal rats and of ascorbic acid and tea in ascorbate-depleted animals. However, the overall sensitivity of rats to dietary facilitators or inhibitors of nonheme iron absorption was not altered dramatically by ascorbic acid depletion. The relative insensitivity of rats to dietary factors affecting nonheme iron absorption in humans is not explained by differences in ascorbic acid metabolism between rats and humans.

Administration, Oral