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Biomedical subjects

J D Cook

Publications and source records attributed to J D Cook.

At least 55 records · Page 3Linked to original sources
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

Large amount of (apo)ferritin in the pancreatic insulin cell and its stimulation by glucose.

In screening a rat pancreatic islet cDNA library by differential hybridization for transcripts increased by glucose, the H chain of ferritin, an iron storage protein, was identified. An ELISA for rat ferritin showed that the insulin cell contains a surprisingly high amount of ferritin comparable to that of iron storage tissues. Most of the ferritin was located in the beta cell, as judged from colocalization of ferritin and insulin by immunohistochemical staining of the pancreas. Islets maintained for 24 h in culture medium containing 20 mM glucose are capable of releasing insulin in response to stimulation with glucose, but islets maintained at 1 mM glucose are incapacitated in response to glucose (see ref 1). Immunoassayable ferritin was threefold higher in 20 mM glucose islets than in 1 mM glucose islets and the glucose-stimulated increase in H ferritin mRNA was confirmed by probing Northern blots of islet RNA with authentic H and L chain cDNAs. This showed that H ferritin mRNA was four- to eightfold higher in 20 mM-glucose islets than in 1 mM glucose islets, whereas L ferritin mRNA was decreased 75-90% in 20 mM glucose islets relative to 1 mM glucose islets. The physiological reason for the abundance of (apo)ferritin in the beta cell is not readily apparent because the islet contains very little iron. Whether or not ferritin is used to handle another metal such as zinc, which is plentiful in the beta cell, is unknown. Another potential reason for ferritin in the beta cell is that ferritin has antioxidant properties and the beta cell is particularly sensitive to oxygen radicals. Regardless of its physiologic purpose, the high amount of ferritin can explain why iron is preferentially retained in the insulin cell and causes diabetes in diseases of iron overloading.

Animals↗
PubMed1994

Identification of the membrane remnants of transferrin receptor with domain-specific antibodies.

Tissue culture studies with K562 and HL60 cells have demonstrated the production of a soluble form of transferrin receptor identical to that identified in human serum. The present study was undertaken to search for membrane remnants of the truncated receptor with peptide antibodies specific for the extracellular and cytoplasmic domain of transferrin receptor. In cell membranes, a 105K remnant was identified that is consistent with truncation of one extracellular domain monomer of the transferrin receptor. In the exosomal fraction of the culture supernatant, a smaller 20K remnant consistent with truncation of both extracellular domains was also demonstrated. These findings provide evidence that soluble receptor is the product of proteolytic cleavage of intact membrane-bound transferrin receptor. Prior studies showing that the concentration of the extracellular domain in exosomes remained stable during incubation in culture supernatant suggest that this cleavage possibly occurs intracellularly.

Amino Acid Sequence↗
PubMed1993

Serum form of the erythropoietin receptor identified by a sequence-specific peptide antibody.

The present investigation was undertaken to search for soluble forms of the erythropoietin receptor in human serum using polyclonal antibody against an amino terminal peptide sequence in the extracellular domain. This sequence was located adjacent to the amino terminus at residues 25-38. When this antibody was used for Western blots of solubilized membranes from nucleated bone marrow cells, a protein consistent with native erythropoietin receptor was seen. Purified soluble ectodomain of the erythropoietin receptor displayed appropriate reactivity with this antibody. When sera from normal subjects and patients with a range of hematologic disorders were examined by Western blotting, a protein with a molecular mass of 34 Kd was detected in sera from patients with enhanced erythropoiesis including sickle cell anemia, thalassemia, and megaloblastic anemia. This protein was rarely detected in normal serum but appeared when normal subjects were treated with recombinant erythropoietin and disappeared after full treatment of patients with megaloblastic anemia due to vitamin B12 deficiency. The protein was not detected after myeloablation for bone marrow transplantation but appeared with marrow engraftment. Reactivity of this protein with the peptide antibody was competitively inhibited by the amino terminal peptide sequence. An additional 48 Kd protein was detected that showed minimal variation in intensity with differing degrees of erythropoietic activity. Detection of this protein could not be inhibited by the addition of synthetic peptide. Our findings indicate the presence of a soluble form of the erythropoietin receptor related to the extracellular domain that is highly correlated with enhanced erythropoiesis.

Amino Acid Sequence↗
PubMed1993

Characterization and quantitation of the circulating forms of serum transferrin receptor using domain-specific antibodies.

To characterize the nature of the immunoreactive transferrin receptor in human serum, antisera were developed to peptide sequences of the extracellular domain of human transferrin receptor between amino acids 107 and 120 and the intracellular domain between amino acids 40 and 54. Antisera against the extracellular domain exhibited reactivity against both purified intact receptor and immunopurified circulating receptor, whereas antisera against the intracellular domain reacted only with intact receptor. Using competitive binding enzyme-linked immunosorbent assays, transferrin receptor in ultracentrifuged sera from normal subjects and patients with sickle cell anemia could be detected with antisera against the extracellular but not the intracellular domain. When the pellet obtained by ultracentrifugation of these sera was assayed after solubilization in 1% teric (polyoxyethylene-9-lauryl ether), only 0.6% of total serum receptor was detected in normal subjects and 3.8% in subjects with sickle cell disease. Roughly equal amounts of this pelleted immunoactivity were detected with antibodies against the extracellular and intracellular domains. These results indicate that less than 1% of transferrin receptor in normal human sera is intact receptor consistent with an exosomal origin and that virtually all circulating transferrin receptor is in the form of a truncated extracellular domain.

Amino Acid Sequence↗
PubMed1993

Evaluation of a gastric delivery system for iron supplementation in pregnancy.

The present investigation was undertaken to assess the efficacy of oral iron supplementation during pregnancy by using a gastric delivery system (GDS). Three hundred seventy-six pregnant women between 16 and 35 y of age and 14 and 22 wk gestation were selected if mild anemia was present (hemoglobin concentration 80-110 g/L). The participants were randomly assigned to one of three study groups given no iron, two FeSO4 tablets (100 mg Fe) daily, or one GDS capsule (50 mg Fe) daily. Blood was obtained initially and after 6 and 12 wk for measurement of red blood cell and iron indexes, including serum transferrin receptor. There was a significant and comparable improvement in hematologic and iron-status measurements in the two groups of women given iron whereas iron deficiency evolved in women given no iron supplement. We conclude that by eliminating gastrointestinal side effects and reducing the administration frequency of an iron supplement to once daily, a GDS offers significant advantages for iron supplementation of pregnant women.

Administration, Oral↗
PubMed1993

The clinical significance of serum transferrin receptor levels in sickle cell disease.

Serum transferrin receptor (TfR) levels were measured in 182 children with homozygous sickle cell (SS) disease, 47 with sickle cell-haemoglobin C (SC) disease and 41 normal (AA) controls on their eighth birthday. Highly significant elevations occurred in SS compared to SC disease and in SC disease compared to AA controls. Females had higher levels than males in controls but lower levels than males in SS and SC disease. In SS disease, serum TfR levels tended to rise with age from 2 to 8 years, the change within individuals correlating with a change in reticulocyte count (r = 0.38, P = 0.017) and fall in fetal haemoglobin levels (r = -0.51, P = 0.004). Serum TfR levels did not change with infection or painful crisis but were markedly elevated in hypersplenism and fell following splenectomy in these subjects. In the aplastic crisis, serum TfR levels tended to rise following clinical presentation and then fall, reflecting the reticulocyte counts. These observations are consistent with serum TfR levels being a useful indicator of the degree of erythropoietic expansion in sickle cell disease.

Age Factors↗
PubMed1993

Serum transferrin receptor.

The transferrin receptor plays a critical role in iron metabolism by precisely controlling the flow of transferrin iron into body cells. A soluble truncated form of the receptor can be detected in human serum using sensitive immunoassays, and the initial clinical experience with this new measurement indicates that it reflects the total body mass of tissue receptor. Serum receptor levels rise significantly with tissue iron deficiency and the heightened demand for iron associated with expansion of the erythroid marrow. The serum receptor provides a quantitative measure of functional iron deficiency and distinguishes the associated anemia from that of chronic disease. If iron deficiency is excluded, the serum receptor provides a quantitative measure of total erythropoiesis that is more sensitive and less invasive than bone marrow examination currently used to assess red cell precursor mass. Performed in conjunction with serum ferritin measurements, the serum receptor will be useful in establishing the true prevalence of iron deficiency anemia in population studies.

Anemia↗