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Biomedical subjects

J D Cook

Publications and source records attributed to J D Cook.

At least 145 records · Page 8Linked to original sources
PubMed1983

Low muscle levels of pyridoxine in McArdle's syndrome.

Pyridoxal phosphate is a covalently bound cofactor of glycogen phosphorylase. Phosphorylase is a major muscle protein and therefore represents a significant pool of pyridoxal phosphate. Muscle pyridoxine content was measured in three patients with myophosphorylase deficiency (McArdle's syndrome) in whom there was a marked diminution or absence of phosphorylase protein as determined by acrylamide gel electrophoresis. Total muscle pyridoxine in the patients with McArdle's syndrome (0.55 +/- 0.08 microgram/g wet weight, mean +/- SD) was markedly reduced compared with 11 human control subjects who had normal levels of muscle phosphorylase (total muscle B6 = 2.49 +/- 0.47). Despite such drastically low levels of muscle pyridoxine, these patients had no evidence of pyridoxine "deficiency." These results suggest that low muscle B6 in McArdle's syndrome represents the specific loss of pyridoxal phosphate normally bound to phosphorylase apoenzyme and imply that phosphorylase pyridoxal phosphate accounts for 75 to 80 percent of the total pyridoxine in normal human muscle.

Adolescent↗
PubMed1983

Myofibrillar creatine kinase in Duchenne and avian muscular dystrophy.

The presence and activity of the fraction of creatine kinase (CK) which was associated with myofibrils and located in the M line of the sarcomeres was determined in normal and dystrophic avian muscle and in normal and dystrophic (Duchenne) human muscle. Myofibrils were isolated from homogenates of muscle and washed nine times so as to remove nonmyofibrillar CK. In myofibrils from dystrophic muscle the enzyme CK was localized to the M line using immunofluorescent techniques and was enzymatically active. These results suggest that in both avian and Duchenne muscular dystrophy, there is not a myofibrillar disorder of the phosphocreatine shuttle.

Adult↗
PubMed1983

The use of capillary blood for measurements of circulating ferritin.

The accuracy and reproducibility of using stored capillary blood for measurements of circulating ferritin were evaluated by comparison with simultaneous measurements on venous blood. In an initial study, the between- and within-sample variability of capillary determinations was about three times higher than with venous measurements, but the difference was reduced considerably by using capillary serum rather than plasma. With both serum and plasma, the mean ferritin in capillary specimens was 3 to 5% higher than in venous blood. These minor drawbacks with capillary measurements are outweighed by the benefit of improved compliance in prevalence surveys when finger-stick sampling can be used in place of venipuncture.

Adult↗
PubMed1983

Inhibition of food iron absorption by coffee.

Dual isotope studies were performed in iron replete human subjects to evaluate the effect of coffee on nonheme iron absorption. A cup of coffee reduced iron absorption from a hamburger meal by 39% as compared to a 64% decrease with tea, which is known to be a potent inhibitor of iron absorption. When a cup of drip coffee or instant coffee was ingested with a meal composed of semipurified ingredients, absorption was reduced from 5.88% to 1.64 and 0.97%, respectively, and when the strength of the instant coffee was doubled, percentage iron absorption fell to 0.53%. No decrease in iron absorption occurred when coffee was consumed 1 h before a meal, but the same degree of inhibition as with simultaneous ingestion was seen when coffee was taken 1 h later. In tests containing no food items, iron absorption from NaFeEDTA was diminished to the same extent as that from ferric chloride when each was added to a cup of coffee. These studies demonstrate that coffee inhibits iron absorption in a concentration-dependent fashion.

Adolescent↗
PubMed1983

Iron fortification: an update.

Iron fortification is the optimal approach to reducing the high prevalence of iron deficiency in developing countries. Selection of the iron source entails a compromise between the use of inert compounds which are poorly absorbed and chemically reactive forms with high bioavailability. Although the vehicle and fortification compound must be chosen in tandem because most iron compounds cause discoloration or rancidity, the emphasis in this review is on the food vehicle. Technology for fortifying wheat flour and bread is well established and the use of these vehicles has probably had a significant impact on iron status in Western countries. Recent studies in India indicate that the fortification of common salt is technically feasible and field trials have shown a good hematological response. Similar success has been achieved by fortifying refined sugar with NaFeEDTA in Guatemala. Rice has advantages as a vehicle in those areas where it is the staple food but the technology requires further development. Fish-based condiments have been successfully fortified with NaFeEDTA and show promise as a vehicle in East Asian countries. The fortification of infant foods poses no technical problems and should be encouraged. Additional work is needed to identify other fortification options and to develop targeted fortification programs that will direct iron to those segments of a population in greatest need.

Anemia, Hypochromic↗
PubMed1983

Hyperkinetic circulation during exercise in neuromuscular disease.

Increased oxygen transport by the circulation is normally tightly coupled to increased oxygen uptake (VO2) during exercise; cardiac output (Q) increases 5 to 6 liters for every liter of increased oxygen utilization (delta Q/delta VO2 congruent to 5). We measured cardiac output and oxygen uptake at rest and during bicycle exercise in 7 patients with myalgia without evident muscle disease and 15 patients with myopathies. Resting circulation was normal in all patients, and during exercise the increase in cardiac output relative to oxygen uptake was normal in all myalgia and most myopathy patients. However, in four patients (with dermatomyositis, phosphorylase deficiency, carnitine deficiency, and ocular myopathy with "ragged-red fibers") exercise cardiac output was excessive and delta Q/delta VO2 high, resulting in an abnormally high level of cardiac work for a given level of exercise. This hyperkinetic response may represent aberrant regulation of the circulation by skeletal muscle as a consequence of some myopathies.

Adolescent↗
PubMed1983

Heterogeneity of tropomyosin and actin in normal and diseased muscle.

Actin and tropomyosin in muscle samples from normal humans, from human fetuses between 12 and 17 gestational weeks, and from patients with a variety of neuromuscular disorders were studied with two-dimensional electrophoresis using isoelectric focusing with either a broad pH range (8.6-4.5) or a narrow pH range (5.9-3.8) for the first dimension and either SDS or SDS-urea for the second dimension. With the broad pH range, two brothers with Duchenne muscular dystrophy were noted to have a less acidic variant of alpha-tropomyosin in biceps muscle which was not found in biceps muscle from other patients or controls. Studies of 8 additional biopsy specimens from patients with Duchenne muscular dystrophy and comparison with both fetal and normal human muscle using the narrow pH range revealed multiple forms of actin and tropomyosin which varied from individual to individual. This heterogeneity appeared to be unrelated to the dystrophic state but also obscured the ability to detect a change in actin or tropomyosin which could be related to dystrophy.

Actins↗
PubMed1983

The effect of suboptimal concentrations of mitogens on the immunosuppressive action of azathioprine and prednisolone on human lymphocytes in vitro.

The interaction of two commonly used immunosuppressive agents, azathioprine (AZA) and prednisolone sodium succinate (PSS), with three mitogens, Concanavalin A (Con A), phytohemagglutinin (PHA), and pokeweed mitogen (PWM) was studied. Using the endpoint of 50% inhibition of 3H-thymidine incorporation (ID50) as an indicator of cellular replication, the affect of suboptimal and optimal concentrations of mitogen on the immunosuppressive action of AZA or PSS on human lymphocyte replication in vitro was determined by isobolic analysis. The AZA ID50 for optimal concentrations of Con A (60 mcm/cc) was 242 +/- 21 ngm/cc (mean +/- SEM, n = 8), and at a suboptimal concentration of Con A (20 mcg/cc) it was 233 +/- 42, i.e., the AZA ID50 was independent of the concentration of Con A. This same independent interaction was found for PHA and PWM. However, at the optimal concentration of Con A (60 mcg/cc) the PSS ID50 of 523 +/- 55 ngm/cc was significantly higher (p less than 0.001) than the PSS ID at the suboptimal concentration of Con A (20 mcg/cc) which was 234 +/- 24 ngm/cc. A similar antagonistic interaction was found between PSS and either PHA or PWM. These findings emphasize the importance of accurately defining the testing parameters when assessing a drug's effect on lymphocyte proliferation. The data, along with other studies, support the hypothesis that drugs which directly interfere with DNA synthesis will not be affected by the strength of the signal for cellular replication, whereas those that modulate cellular replication are affected by the strength for lymphocyte replication.

Adult↗
PubMed1983

Effect of fiber on nonheme iron absorption.

The effect of fiber on the absorption of food iron was examined by performing multiple radioiron absorption tests in normal male and female subjects. In an initial study, we added bran, pectin, or cellulose to muffins prepared with wheat flour. Because of the low values obtained in this study, another study was done in which apple juice containing 50 mg of ascorbic acid was added to the meal to increase iron absorption averaged 2.26% from plain muffins, 1.07% from bran muffins, 1.89% from pectin muffins, and 2.26% from cellulose muffins. Only the effect of bran was statistically significant. We next designed two complex meals that differed maximally in their content of naturally occurring fiber but that were matched with respect to macronutrient, mineral, iron, and ascorbic acid contents. Mean absorptions from the low- and high-fiber meals were significantly different, averaging 6.07% and 2.96%, respectively. These results demonstrate that inhibition of iron absorption is not a universal property of all fiber sources. Moreover, the relatively modest effect of maximally altering the natural fiber content of a meal suggests that fiber is not a major determinant of food iron availability in humans.

Adolescent↗
PubMed1983

The effect of food consistency on iron absorption.

Iron absorption and the half-time of gastric emptying were measured concurrently in 13 normal volunteer subjects. Each subject ate two test meals of identical composition; one meal was prepared and served in the usual manner while the second was homogenized before serving. No correlation was found between the half-time of gastric emptying and the absorption of either heme or nonheme iron among subjects eating the conventional meal. Homogenization of the meal led to a 31% fall in the mean half-time of gastric emptying and an increase in iron absorption of 22% for nonheme and 42% for heme. These findings indicate that the physical form of a meal has a modest effect on iron absorption.

Adult↗
PubMed1982

HLA and the response of lymphocytes to viral antigens in patients with multiple sclerosis.

Serum antiviral antibody titers, presence of lymphocytotoxic antibodies, and lymphoproliferative responses to viral antigens were determined in 44 multiple sclerosis (MS) patients and 25 healthy subjects. These measurements were correlated with the HLA type and the clinical characteristics of the patients. The Dw2/DR2 phenotype, known to be associated with increased MS susceptibility, was also associated with a later onset of MS and more rapid progression of disease. Within the DW2/DR2 group, the disability status and rate of progression did not correlate with the relative degree of lymphoproliferative response. Patients with the Dw2/DR2 phenotype had similar lymphoproliferative responses to all viral antigens as control subjects possessing or lacking Dw2/DR2. Patients lacking Dw2/DR2 had increased lymphoproliferative responses selectively to measles virus when compared with normal subjects or Dw2/DR2 positive individuals. Absence of the B40 antigen was associated with high antibody titer to measles, and presence of the Dw7/DR7 antigens was associated with high titers against herpes simplex I virus. Both B40 and Dw7/DR7 phenotypes were associated with decreased occurrence of lymphocytotoxic antibodies. The Dw7/DR7 phenotype has been associated in previous studies with a decreased susceptibility to MS. These results, therefore, suggest that both humoral and cellular antiviral immune mechanisms in man are under the influence of HLA-linked genes. Progression of lack of progression in MS cold in turn be somehow related to the differing strength of antiviral immune responses in individuals of the appropriate HLA genotype.

Antibodies, Viral↗
PubMed1982

Absorption of controlled-release iron.

A multiple-dose double radioiron technic was used to compare absorption of iron administered as a controlled release (CR) capsule and as an elixir; both formulations contained 50 mg elemental iron as ferrous sulfate. When taken by normal subjects in the fasting state, mean absorption from the elixir and CR capsule averaged 4.92% and 4.38%, which gave a CR capsule:elixir ratio of 0.89. This difference was not significant, but when taken with meals that inhibit absorption of dietary iron by different degrees, absorption of the CR formulation was superior. CR capsule:elixir absorption ratios averaged 1.70 from a meal that is mildly inhibitory and 3.13 from a meal that causes more marked inhibition. It is concluded that CR iron formulations may offer a therapeutic advantage to patients who take oral iron with meals to avoid gastrointestinal side effects.

Adult↗
PubMed1982

Reduction of the soy-induced inhibition of nonheme iron absorption.

Recent studies in normal men have demonstrated that soy products have a pronounced inhibitory effect on the absorption of nonheme dietary iron. The purpose of the present investigation was to explore approaches to overcoming this inhibition. A modest but significant increase in iron absorption was observed when test meals containing either isolated soy protein or whole soybeans were baked at 200 degrees C. The addition of 100 mg ascorbic acid to a meal containing isolated soy protein had a more dramatic effect, increasing mean absorption from 0.6 to 3.2%. A similar but less pronounced increase was observed when meat was added to the isolated soy protein meal. These results indicate that the inhibitory effect of soy can be reversed to some extent by substances known to enhance nonheme iron absorption.

Adolescent↗
PubMed1982

Iron status of elderly Americans.

Studies of iron nutriture in the elderly are limited and very few include observations on individuals over the age of 75. The two Health and Nutrition Examination Surveys carried out by the United States Department of Health, Education and Welfare demonstrate that the mean iron intake of Americans is adequate until the age of 75. However, with changes in the major food sources there is a decrease in iron derived from meat and a concomitant rise in the proportion supplied by breakfast cereals. Alterations in dietary iron bioavailability++ that may result from this have not been studied. Physiological data suggest that the elderly do not represent a target population for iron deficiency since iron requirements are no greater than those of adult men and lower than those of children and menstruating women. Furthermore, there is little direct evidence of a high prevalence of iron deficiency in the elderly, but the laboratory measurements that have proved useful in defining iron status in younger people have not been standardized for or extensively used in older people. Anemia is still the most important known consequence of significant iron deficiency. However, the application of Hb or hematocrit standards used in younger people to the elderly as well as the assumption that anemia can be equated with iron deficiency invalidates the conclusions of many surveys. Hb and hematocrit measurements are not suitable screening tests for iron deficiency in the elderly and there is an urgent need for a clearer understanding of the physiological and nutritional factors responsible for lower Hb values in older people, particularly older Blacks.

Adolescent↗
PubMed1982

Clinical evaluation of iron deficiency.

While the prevalence of iron deficiency has remained relatively constant, there has been continuing refinement in its laboratory recognition, especially with the recent introduction of serum ferritin and FEP measurements. It is helpful to classify iron deficiency into three stages. Storage iron depletion is identified by marrow examination or serum ferritin, iron deficient erythropoiesis by TS, FEP, or MCV, and iron deficiency anemia by hemoglobin concentration or therapeutic iron trial. Combinations of these measurements have been used in prevalence studies to obtain a quantitative measure of body iron stores. The optimal laboratory approach to diagnosing iron deficiency depends on the clinical setting. In the office or outpatient clinic, iron depletion is best recognized by the serum ferritin, although the TS, FEP, and MCV are helpful in gauging its severity. In hospitalized patients with overt anemia, the TS, FEP, and MCV are much less helpful because similar changes are seen in the anemia of chronic disease. Examination of marrow iron remains the method of choice, especially in patients with infection, chronic disease, malignancy, or liver disease, although in many clinical situations the same information can be obtained from a serum ferritin. Serial measurements of serum ferritin have been particularly useful in monitoring patients at high risk of iron deficiency such as those with rheumatoid arthritis, chronic inflammatory bowel disease, or chronic renal failure.

Adult↗