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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

Post-traumatic stress disorder and coping in veterans who are seeking medical treatment.

The present study examined psychological coping styles and mental health treatment histories in veterans with PTSD. This study also served as a replication and extension of an earlier investigation that assessed the prevalence of PTSD in World War II, Korea, and Vietnam combat veterans who were seeking medical treatment. Thirty-six combat veteran medical patients were compared to 38 war-era controls. Nearly a third of the combat veterans met psychometric criteria for PTSD; none of the controls met these criteria. Both PTSD-positive subjects and mental health treatment seekers showed a significantly greater use of emotion-focused coping. Results also showed that Vietnam combatants were more likely to have received individual mental health treatment. These findings and their treatment implications are discussed.

Adaptation, Psychological

Soy protein, phytate, and iron absorption in humans.

The effect of reducing the phytate in soy-protein isolates on nonheme-iron absorption was examined in 32 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 one of a series of soy-protein isolates with different phytate contents. Iron absorption increased four- to fivefold when phytic acid was reduced from its native amount of 4.9-8.4 to less than 0.01 mg/g of isolate. Even relatively small quantities of residual phytate were strongly inhibitory and phytic acid had to be reduced to less than 0.3 mg/g of isolate (corresponding to less than 10 mg phytic acid/meal) before a meaningful increase in iron absorption was observed. However, even after removal of virtually all the phytic acid, iron absorption from the soy-protein meal was still only half that of the egg white control. It is concluded that phytic acid is a major inhibitory factor of iron absorption in soy-protein isolates but that other factors contribute to the poor bioavailability of iron from these products.

Absorption

Congenital muscular dystrophy with abnormal radiographic myelin pattern.

We report 11 children with a homogeneous clinical syndrome affecting both sexes, characterized by weakness at birth, slowly improving course, weakness of all muscle groups, arreflexia, elevated blood creatine kinase, normal nerve conduction velocity, dystrophic changes on muscle biopsy, and diffuse periventricular cortical white-matter abnormalities with sparing of corpus callosum, internal capsule, and brain stem. We compare them to 48 other previously reported similar cases and designate them as altered myelin radiographic pattern congenital muscular dystrophy (CMD), which is the same as occidental CMD. We compare them to the other presently accepted phenotypes: progressive Fukuyama CMD, Walker-Warburg or cerebral-ocular CMD, and Santavuori or muscle-eye-brain CMD. We suggest that the different phenotypes are alleles of the same gene, which regulates or expresses a structural protein required for muscle integrity, myelination, and formation of the cortex. Such phenotypic diversity has been established for mutations of Xp21 in X-linked muscular dystrophies.

Biopsy

Riyadh chromosome breakage syndrome: mental retardation with depigmentation of the skin and hair.

A 20-month-old infant with "silvery-blond" hair color, widespread confettilike depigmentation of the skin, and mental retardation was found to have, in lymphocytes and fibroblast cultures, increased spontaneous chromosome breaks and breaks induced by both mitomycin and gamma-irradiation. The sister chromatid exchange frequency was normal. This child probably represents a new chromosome breakage syndrome.

Albinism

Effect of enhanced erythropoiesis on iron absorption.

To examine the influence of erythropoiesis on iron absorption, radioiron absorption tests were performed in normal subjects before and after a course of recombinant erythropoietin. The absorption of heme and nonheme iron from a standard meal was measured in nine subjects, and the absorption of a therapeutic dose of ferrous sulfate given with or without food was determined in an additional 11 subjects. The subcutaneous administration of 100 U recombinant human erythropoietin/kg body weight given on 10 successive days over a 2-week period induced a brisk increase in erythropoiesis and a sharp decrease in iron stores. With the standard meal, there was a modest increase in heme iron absorption from 47.0% to 58.6% (p < 0.05) and a dramatic five-fold rise in nonheme iron absorption from 5.9% to 31.8% (p < 0.001). The absorption of 50 mg iron as ferrous sulfate increased from 2.0% to 17.9% when given with food (p < 0.001) and from 7.0% to 24.6% when given with water (p < 0.001). To assess the effect of erythropoiesis independently of the induced changes in iron status, the absorption data were adjusted to a common serum ferritin level. The relative increase in iron absorption was still significant for both dietary nonheme iron (ratio 2.51, p < 0.02) and ferrous sulfate given with food (ratio 2.99, p < 0.01). It is concluded that the striking enhancement of iron absorption following regular erythropoietin administration in normal subjects is related to the combined effect of diminished iron stores and augmented erythropoiesis.

Adult

Serum transferrin receptor distinguishes the anemia of chronic disease from iron deficiency anemia.

Recent studies have shown that the serum transferrin receptor is a sensitive, quantitative measure of tissue iron deficiency. This study was undertaken to determine the serum transferrin receptor's ability to distinguish iron-deficiency anemia from the anemia of chronic inflammation and to identify iron deficiency in patients with liver disease. The mean transferrin receptor level in 17 normal controls was 5.36 +/- 0.82 mg/L compared with 13.91 +/- 4.63 mg/L in 17 patients with iron-deficiency anemia (p less than 0.001). The mean serum receptor level was normal in all 20 patients with acute infection, including five with acute hepatitis, and was also normal in 8 of 10 anemic patients with chronic liver disease. Receptor levels were in the normal range in all but 4 of 41 patients with anemia of chronic disease. We conclude that unlike serum ferritin levels, which are disproportionately elevated in relation to iron stores in patients with inflammation or liver disease, the serum transferrin receptor level is not affected by these disorders and is therefore a reliable laboratory index of iron deficiency anemia.

Anemia

Ferrous fumarate fortification of a chocolate drink powder.

An evaluation was made into the usefulness of ferrous fumarate as an iron fortificant for an experimental chocolate drink powder targetted to children and adolescents. Organoleptically ferrous furmarate was acceptable when the chocolate drink powder was reconstituted in milk or water that was heated to less than 80 degrees. Unacceptable colour changes occurred, however, when boiling milk or water were used. In human Fe absorption studies when the Fe compounds were added to the chocolate drink immediately before consumption, ferrous fumarate was 3.31% absorbed compared with 2.82% for ferrous sulphate and 2.11% for ferric pyrophosphate. When the Fe compounds were processed during the manufacture of the chocolate drink powder, the absorption of ferrous furmarate was 5.27%, ferrous sulphate 2.62% and ferric pyrophosphate 0.55%. Ascorbic acid had little or no effect on the absorption of ferrous furmarate. It is concluded that food processing can influence the relative absorption of fortification Fe and that, if not reconstituted with boiling milk or water, ferrous fumarate could be a useful compound for the fortification of chocolate drink powders.

Adolescent

Calcium supplementation: effect on iron absorption.

The influence of calcium supplements on the absorption of dietary nonheme iron and of iron supplements was evaluated in 61 normal volunteer subjects by use of a double-radioisotope technique. When taken without food, calcium carbonate did not inhibit the absorption of ferrous sulphate with doses of either 300 mg Ca and 37 mg Fe or 600 mg Ca and 18 mg Fe. However, at the latter levels, calcium citrate and calcium phosphate reduced iron absorption significantly by 49% and 62%, respectively. All calcium supplements inhibited absorption of the iron supplement when taken with food. The absorption of dietary nonheme iron was also inhibited by all three supplements. This inhibition was less pronounced from a meal of high iron availability and low calcium content (28%) than from a breakfast meal of low iron availability and high calcium content (55%). These results suggest that taking regular calcium supplements with meals makes it more difficult for women to meet their daily iron requirement.

Absorption

Assessment of the role of nonheme-iron availability in iron balance.

To assess the nutritional relevance of absorption studies that use extrinsically labeled single meals, we developed a method for measuring nonheme-iron absorption from the diet and compared the results with absorption from single meals. When subjects consumed their usual diet, there was good agreement between dietary absorption (6.4%) and representative single meals fed in the laboratory (6.1%). Nonheme-iron availability, as estimated by a model that incorporated the effect of both enhancers and inhibitors, correlated significantly with absorption from single meals but not with dietary absorption. When the diet was modified to promote iron absorption maximally, dietary absorption increased only slightly (8.0%) and remained significantly lower than it was from single meals (13.5%). With an inhibitory diet, the decrease in absorption from single meals was similarly exaggerated. These results indicate that in the context of a varied Western diet, nonheme-iron bioavailability is less important than absorption studies with single meals would suggest.

Absorption

Assessment of dietary determinants of nonheme-iron absorption in humans and rats.

Prior investigations have shown that rats are less sensitive than humans to dietary factors that influence the absorption of nonheme iron. This investigation was undertaken to determine whether this disparity is due to differences in the methods used to measure absorption in the two species. By use of identical methodology and test meals, absorption studies were performed in rats and humans to compare the effect of known dietary enhancers (ascorbic acid and meat) and inhibitors (tea, bran, and soy protein) on nonheme-iron absorption. Meat and tea had a marked effect on absorption in humans but did not influence absorption in rats. Although the effect of ascorbic acid, soy protein, and bran on absorption was statistically significant in rats, the absorptive response was far less than it was in humans. Our studies indicate that rodents cannot be used to assess the quantitative importance of dietary factors in human iron nutrition.

Absorption

Serum transferrin receptor for the detection of iron deficiency in pregnancy.

Measurements of circulating transferrin receptor provide a sensitive quantitative index of tissue iron deficiency in otherwise healthy subjects. This investigation was undertaken to examine the diagnostic utility of this new iron index in pregnancy. A battery of iron-related measurements, including serum transferrin receptor concentrations, was performed on 176 women in third-trimester pregnancy who were attending a university prenatal clinic. The mean receptor concentration of 5.96 +/- 2.37 mg/L (+/- 1 SD) did not differ significantly from concentrations in nonpregnant individuals and the frequency distributions were likewise comparable. Elevations in serum receptor greater than 8.5 mg/L occurred only in women with depleted iron stores defined by serum ferritin concentrations. Abnormal concentrations were found in 11 of 13 women with overt iron-deficiency anemia. Our findings indicate that serum receptor concentrations are not influenced by pregnancy per se and are a sensitive index of iron deficiency. By combining serum receptor and serum ferritin measurements, the entire spectrum of iron status in pregnancy can be assessed.

Adolescent

Production of soluble transferrin receptor by K562 erythroleukaemia cells.

The present study was undertaken to examine the production of soluble transferrin receptor by K562 erythroleukaemia cells under controlled experimental conditions. The concentrations of soluble and cellular transferrin receptor were measured by immunoassay employing monoclonal antibodies. Cellular ferritin was also measured as an index of iron supply. With incubation up to 48 h there was a progressive increase in the concentration of soluble transferrin receptor. Manipulating iron supply by adding iron chelators or diferric transferrin to the incubation medium produced marked alterations in cellular receptor and ferritin content. Under all such conditions examined, the relationship between soluble and cellular receptor remained highly constant. These findings support clinical studies of serum receptor suggesting that over a broad spectrum of haematological disorders there is a fixed relationship between serum receptor and tissue receptor mass.

Antibodies, Monoclonal

Stable lyophilized reagents for the serum ferritin assay.

Two monoclonal antibodies to human ferritin, including one that was coupled to horseradish peroxidase, were lyophilized. These reagents show little loss of activity on reconstitution and demonstrate acceptable stability in the accelerated degradation test. When applied in a simple ELISA for the assay of serum ferritin along with the WHO standard for serum ferritin (80/602) they provide a robust assay with standardized reagents which is potentially suitable for use as a reference assay.

Antibodies, Monoclonal

Characterization of transferrin receptor released by K562 erythroleukemia cells.

A soluble form of transferrin receptor has been detected in human serum and has been shown recently to be a truncated form of the intact membrane bound receptor. Mechanisms governing the release of transferrin receptor by cells are poorly understood and could be better defined by tissue culture. The present investigation was undertaken to characterize the transferrin receptor released by K562 erythroleukemic cells. In contrast with maturing sheep reticulocytes, which have been shown to release transferrin receptor in small vesicles termed exosomes, we demonstrated, with a monoclonal enzyme-linked immunoassay, that less than 30% of the transferrin receptor released by K562 cells in log phase growth was in a particulate form. The relative amounts of soluble and particulate receptor released to the supernatant did not change significantly during 48 hr of incubation. Soluble receptor was purified by immunoaffinity chromatography. On polyacrylamide gel electrophoresis, its mobility was the same (85 kDa) as that of the truncated monomeric form recently identified in human serum. Further evidence that serum and soluble receptors released by K562 cells are identical was provided by amino acid sequence analysis, which demonstrated that 16 of the first 19 residues of the N-terminal sequence of soluble K562 receptor are homologous with the serum receptor. The remaining three were not identifiable. K562 cells provide a useful in vitro model for studying the production of membrane-bound and soluble forms of released transferrin receptor.

Amino Acid Sequence

Factors associated with withdrawal bleeding after administration of oral micronized progesterone in women with secondary amenorrhea.

OBJECTIVE: To compare two dosages of oral micronized progesterone (P) and placebo for withdrawal bleeding and side effects. DESIGN: Prospective, randomized, double-blind. SETTING: Academic institution. PARTICIPANTS: Out of 190 screened with oligomenorrhea/amenorrhea, 60 who qualified completed the study. INTERVENTIONS: A 10-day course of (1) oral micronized P 300 mg, (2) oral micronized P 200 mg, or (3) placebo. MAIN OUTCOME MEASURES: Withdrawal bleeding, side effects, and changes in lipids. Endogenous estradiol (E2) concentrations at baseline and P concentrations during treatment were correlated with bleeding response. RESULTS: Withdrawal bleeding occurred in 90% of women taking 300 mg, 58% of women taking 200 mg, and 29% of women taking placebo (P less than 0.0002 for 300 mg versus placebo). Side effects occurred similarly among the groups (P = not significant). Lipid concentrations were unchanged. Endogenous E2 and treatment P concentrations were of limited predictive value for withdrawal bleeding. CONCLUSIONS: Progesterone 300 mg induced significantly more withdrawal bleeding than placebo, with similar side effects. Bleeding response cannot be predicted reliably from E2 and P concentrations.

Administration, Oral

Comparing serum ferritin values from different population surveys.

This report compares serum ferritin data collected in recently conducted Health and Nutrition Examination Surveys by age, sex, and ethnic group. Serum ferritin assays and selected confounding variables are examined to explore the basis of the difference in serum ferritin values obtained from the different surveys.

Confounding Factors, Epidemiologic