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Biomedical subjects

E R Morris

Publications and source records attributed to E R Morris.

At least 37 records · Page 2Linked to original sources

Importance of the rate of hydration of pharmaceutical preparations of guar gum; a new in vitro monitoring method.

Dietary supplements of guar gum are known to improve blood glucose control in diabetic patients. The efficacy of guar is probably dependent mainly upon its capacity to hydrate rapidly and thus to increase viscosity in the small intestine post-prandially. Measurement of the rate of hydration in vitro might therefore be a useful index of the effectiveness of guar formulations. A simple method for monitoring the hydration rate of guar gum has been developed, which involves measuring the changes in viscosity at discrete time intervals over a period of 5 h using a Brookfield RVT rotoviscometer. Six different samples of guar gum (four pharmaceutical preparations and two food grades of guar flour) were hydrated in sealed glass jars rotated at 6 rev min-1 in order to prevent particle aggregation. Marked differences in hydration rate and ultimate (maximum) viscosity between the different guar samples were observed. Three of the four pharmaceutical preparations were lower in viscosity than the food grades of guar flour during the first 60 min of hydration. Two of the preparations hydrated so slowly that even after 5 h they attained viscosity levels of only 60% of their ultimate viscosity. These results may explain why some guar gum preparations are clinically ineffective.

Dietary Fiber↗

Interpretation of the renaturation kinetics of gelatin solutions.

Renaturation kinetics of dilute gelatin solutions are studied by optical rotation and u.v. absorption. Comparing initial slopes of renaturation curves for concentrations below 10 mg.ml-1, the rate limiting process appears as the sum of a constant rate intramolecular nucleation and a bimolecular nucleation. To fit the whole renaturation curves, a kinetic model using Monte Carlo calculations was tested, consisting of random nucleation, rapid total propagation and slow reversion depending on the size of helical segment. Mismatch on the final renaturation extent indicates that propagation is more limited than proposed.

Gelatin↗

Comparison of in vitro, animal, and clinical determinations of iron bioavailability: International Nutritional Anemia Consultative Group Task Force report on iron bioavailability.

Relative bioavailability of two iron fortificants, electrolytic Fe and ferric orthophosphate, was related to that of the reference ferrous sulfate with in vitro and rat model depletion-repletion methods in four laboratories to compare values directly with those obtained in a parallel human study. In vitro testing was performed on Fe compounds with both solubility and dialysis in a simulated in vitro gastrointestinal digestion system. Two depletion-repletion techniques, hemoglobin-regeneration efficiency (HRE) and an official method of the Association of Official Analytical Chemists (AOAC), were examined. AOAC relative biological values (RBV) of electrolytic Fe were 0.66 and 0.78 and of FePO4 were 0.25 and 0.34. HRE values were 0.78 and 0.58 for electrolytic Fe and FePO4, respectively. When compared with FeSO4 in a radiolabeled farina-based meal fed to humans, the RBV of FePO4 was 0.25 and electrolytic Fe 0.75. Results obtained with the AOAC method serve as the most reliable prediction of Fe bioavailability in the human although in vitro dialysis is a promising screening technique.

Animals↗

Submaxillary mucins. Intermolecular interactions and gel-forming potential of concentrated solutions.

The intermolecular interactions in concentrated solutions of pig submaxillary mucin (PSM) and sheep submaxillary mucin (SSM) were studied by mechanical spectroscopy. PSM and SSM were purified from detectable protein and nucleic acid by equilibrium centrifugation in a CsCl density gradient. PSM and SSM isolated in the presence of proteinase inhibitors showed distinct differences from preparations isolated in the presence of 0.2 M-NaCl alone, the latter having a carbohydrate and amino acid analysis similar to other preparations isolated by precipitation or ion-exchange techniques. Gel-filtration studies showed that preparations isolated in the presence of 0.2 M-NaCl alone were dissociated into smaller-sized glycoprotein units by 3.5 M-CsCl or 2.0 M-NaCl (SSM), pH 2.0 (PSM) or heating at 100 degrees C for 10 min (PSM and SSM). Preparations isolated in the presence of proteinase inhibitors were not dissociated by these treatments. Proteolysis fragmented all submaxillary mucin preparations into small glycopeptides of Mr 13,700 for PSM and of Mr 14,000 and 15,000 for SSM. PSM preparations when concentrated formed viscoelastic gels, as determined by mechanical spectroscopy. In contrast, SSM showed characteristics of a weak viscoelastic liquid under comparable conditions (coil overlap). PSM glycoprotein isolated in proteinase inhibitors formed weak viscoelastic gels at concentrations between 5 and 15 mg/ml. Preparations of PSM glycoprotein isolated in the presence of 0.2 M-NaCl (concentration 10-97 mg/ml) had the same overall mechanical gel structure as those preparations extracted in the presence of proteinase inhibitors. This gel structure was seen to collapse following proteolysis of both preparations or after acid treatment of the glycoprotein isolated in the presence of 0.2 M-NaCl, consistent with the breakdown in size of the polymeric glycoprotein. Treatment of PSM gel with 0.2 M-2-mercaptoethanol caused a surprising increase in gel strength, which was further markedly increased on removal of the reducing agent by dialysis. An association of reduced subunits of PSM was observed by gel filtration after removal of 0.2 M-2-mercaptoethanol. These results point to intermolecular disulphide exchange occurring on reduction of these PSM glycoprotein preparations. These results demonstrate that gel formation in PSM glycoprotein is similar to that for other gastrointestinal mucus glycoproteins from stomach to colon. Gel formation in PSM, as in other mucins, depends on polymerization of subunits.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Mucus glycoprotein gels. Role of glycoprotein polymeric structure and carbohydrate side-chains in gel-formation.

The structure of mucus glycoprotein gels from the pig gastrointestinal tract was investigated by mechanical spectroscopy. Gastric, duodenal, and colonic mucus had the same mechanical profile, characteristic of a viscoelastic gel. The gel structure collapsed on destruction of the polymeric structure of the component glycoprotein by reduction with 0.2M mercaptoethanol or after proteolysis with papain. The progressive weakening of mechanical properties and the decrease in polymeric glycoprotein content were measured as functions of time of reduction. A linear correlation was obtained between the gel quality [defined by tan delta, the ratio of the loss modulus (G'') to the storage modulus (G')] and the proportion of polymeric to subunit glycoprotein in the mucus. Purified mucus glycoprotein, at the same concentration as that in native mucus, resulted in a gel with mechanical properties no different from those of the respective native secretion, demonstrating that the glycoprotein alone could reproduce the gel-forming properties of mucus. After proteolytic digestion, all native secretions and reconstituted mucus showed an absence of Newtonian behaviour in the frequency dependence of dynamic viscosity at low frequencies. This provided evidence that the noncovalent interactions, characteristic of the native gel matrix, were still present after proteolytic digestion when the nonglycosylated protein core accessible to proteinases had been removed. These results were interpreted to show (a) a common mechanism for gel-formation in gastric, duodenal, and colonic mucus; (b) that the polymeric structure of mucus glycoproteins confers the three-dimensional structure necessary for formation of the gel network; and (c) that noncovalent interactions which arise between the glycoprotein molecules by relatively stable interdigitation of the carbohydrate side-chains are involved in formation of the gel network.

Animals↗

Alteration of multiple cell membrane functions in L-6 myoblasts by T-2 toxin: an important mechanism of action.

Recent studies suggest that T-2 toxin interacts with cell membranes and alters membrane function. This study was done to assess the effect of T-2 toxin on a broad range of cell membrane functions in L-6 myoblasts. The following parameters were assessed after exposure to T-2 toxin for 10 min: (1) the uptake of calcium, rubidium, and glucose; (2) the uptake of leucine and tyrosine and incorporation into protein; (3) the uptake of thymidine and incorporation into DNA; and (4) residual cellular lactate dehydrogenase (LDH) as a measure of cell membrane integrity. The effects of T-2 toxin on these parameters were: (1) The minimal effective concentration (MEC) of T-2 toxin that caused a reduction in the uptake of calcium and glucose was 4 pg/ml. The uptake of rubidium was increased at 0.4 pg/ml and then reduced at 4 pg/ml and higher concentrations. (2) The MEC for reduction of the uptake of leucine and tyrosine and their incorporation into protein was 4 pg/ml. (3) Thymidine uptake and incorporation into DNA showed a biphasic response with an increase at 0.4 pg/ml and a reduction at 4 pg for uptake and 40 pg/ml for incorporation. (4) Intracellular LDH was reduced at 4 ng/ml. (5) Calcium efflux was reduced after 1-, 5-, and 15-min exposures to T-2 toxin in a concentration of 40 ng/ml. All of the changes noted, including protein synthesis inhibition, were present to a significant degree within 10 min of exposure to T-2 toxin. This time interval is too short to attribute all of these effects directly to protein synthesis inhibition since most short-lived proteins have half-lives measured in hours. In conclusion, T-2 toxin appears to have multiple effects on cell membrane function at very low concentrations (0.4 pg/ml to 4 ng/ml), which are independent of protein synthesis inhibition. These likely include effects either direct or indirect on amino acid, nucleotide, and glucose transporters, as well as calcium and potassium (rubidium) channel activities.

Calcium↗

Vacuum ultraviolet circular dichroism of fibronectin. Dominant tyrosine effects.

The spectroscopic authenticity of a very intense negative band at about 183 nm reported previously from conventional circular dichroism (c.d.) studies of bovine plasma fibronectin has now been confirmed by vacuum ultraviolet c.d. measurements on two prototype spectrometers, one using a conventional light source and the other using synchrotron radiation. Closely similar spectra were obtained from both instruments, and from both solid films and solutions. The spectra show no obvious parentage in the known c.d. of the peptide backbone, but have marked similarities to the c.d. of N-acetyltyrosineamide, both in the strong band at 183 nm and in a characteristic positive band at 230 nm, It is concluded that the c.d. of fibronectin is dominated by contributions from tyrosine side-chains and that, as suggested previously, these may provide a sensitive probe for molecular organization and interactions.

Circular Dichroism↗

Long-term consumption of beef extended with soy protein by children, women and men: III. Iron absorption by adult men.

Forty-nine ostensibly healthy men consumed either patties of all-beef or beef extended with soy-isolate, -concentrate or -flour as the principal protein source in 1 to 2 meals daily for 180 days. Iron status was monitored by absorption of radioiron from a reference dose of ferrous ascorbate and by serum ferritin concentration. In addition, nonheme iron absorption from a test meal of the respective beef pattie consumed for the 180 days was estimated by the extrinsic tag procedure. There was no detrimental effect on iron stores as indexed by reference ferrous ascorbate absorption or serum ferritin concentration. Absorption of nonheme iron from the test meals was low except for individuals having indices of low iron stores. When adjusted for the effect of level of iron stores the relative absorption of nonheme iron from soy-isolate and -flour containing meals was greater than from the all-beef meal, indicating marked differences in the effect on iron absorption by different soy products. Consumption of soy-extended beef should have no detrimental effect on iron status of adult men if consumed in mixed diets at the level used in this study.

Adolescent↗

Mechanical characterization and properties of gastrointestinal mucus gel.

Mechanical spectroscopy has been used to study the structure of mucus gel taken from the surface of the pig gastrointestinal tract. Mucus from stomach, duodenum and colon was insoluble and its mechanical properties, characteristic of a weak viscoelastic gel, were unchanged in saline, acid (pH 2) and denaturants. Small intestinal mucus gel which was of poorer quality, was disrupted following exposure to acid and denaturants. Concentration of purified glycoprotein produced gels that had mechanical spectra with the same profiles as the respective native secretion except for reconstituted small intestinal mucus which was of better quality and similar to the other native and reconstituted gels. Reduction of S-S linkages or proteolysis of all mucus gels caused a collapse of structure to give profiles typical of a viscous solution. This collapse of gel structure was shown to result from a breakdown of the covalent polymeric structure of the component glycoproteins. A linear correlation for mucus gels was observed between gel quality (as defined by tan delta) and the ratio of polymeric glycoprotein to its degraded lower molecular weight subunit. Human gastric mucus from a histologically normal stomach also had the characteristics of a weak viscoelastic gel, although that from patients with peptic ulcer disease has a significantly reduced content of polymeric glycoprotein.

Animals↗

Phytate:zinc and phytate X calcium:zinc millimolar ratios in self-selected diets of Americans, Asian Indians, and Nepalese.

The literature indicates that phytate:zinc and phytate X calcium:zinc millimolar ratios of a diet may provide useful indexes of the bioavailability of dietary zinc. However, there is little information on the phytate:zinc and phytate X calcium:zinc millimolar ratios for total human diets. We have therefore determined the phytate:zinc and phytate X calcium:zinc millimolar ratios of self-selected diets of 29 American omnivores, 23 American vegetarians, 30 Asian Indian immigrant vegetarians, and 26 Nepalese lactating vegetarians. Criteria for selection of subjects were: good health, no extreme dietary habits, and no intake of nutrient supplements. According to the limited literature, the suggested critical values for phytate:zinc and phytate X calcium:zinc millimolar ratios in animal diets and retrospective calculations from human diets are greater than 10 and greater than 200, respectively. The mean phytate:zinc and phytate X calcium:zinc millimolar ratios of American omnivorous diets in the present study were less than 10 and 200, respectively. Confirmation of the critical molar ratios as indexes of the bioavailability of zinc in human diets has not been established by experimentation. However, if the data from animal studies are applicable to human diets, the present study suggests that phytate has little influence on zinc bioavailability of most American diets. In contrast, the mean phytate:zinc and phytate X calcium:zinc millimolar ratios of all vegetarian diets were above the proposed critical levels. Those data, therefore, suggest that phytate might increase the risk of impaired zinc bioavailability for vegetarians consuming a relatively high level of calcium.

Biological Availability↗

Solid-state 13C NMR and X-ray diffraction of dermatan sulfate.

Dermatan sulfate in the solid state has been studied by 13C CP/MAS nmr and X-ray diffraction in order to establish the ring conformation of the L-iduronate moiety. The solid state nmr spectrum is similar to the solution spectrum obtained previously, indicating that a ring conformation at least approximating to 1C4 predominates in the solid state. X-ray powder diffraction data from the same sample indicate the presence of the 8-fold helix form previously observed by fiber diffraction, and interpreted in terms of a 4C1 ring form. A likely explanation of the results is that a distorted 1C4 L-iduronate ring conformation, not considered in the initial X-ray analysis, may emerge to provide a satisfactory interpretation of all available physical-chemical data.

Animals↗

Properties of gastric and duodenal mucus: effect of proteolysis, disulfide reduction, bile, acid, ethanol, and hypertonicity on mucus gel structure.

Small deformation oscillatory rheologic measurements have been used to investigate the structure of human and pig gastric mucus and pig duodenal mucus. All three secretions had viscoelastic properties characteristic of water-insoluble, viscoelastic gels. Mucus will flow and anneal if damaged, due to the making and breaking of its elastic structure, the measured lifetime of which was 10-120 min. Mucus reconstituted by concentration of the purified glycoprotein (pig gastric and duodenal mucus) had the same viscoelastic properties as the fresh mucus, giving evidence that the glycoprotein alone will reproduce the rheologic characteristics of the mucus. The structure of fresh mucus gel was unaffected by prolonged exposure to the following mucosal damaging agents: undiluted pig bile, 20 mM sodium taurocholate or 20 mM sodium glycocholate (all at pH 2, 6, and 8), HCl at pH 1, 2 M NaCl, and ethanol less than 40% (vol/vol). Higher concentrations of ethanol greater than 40% (vol/vol), caused dehydration and denaturation of mucus. Proteolysis by pepsin and other enzymes resulted in solubilization of the mucus gel with a complete change in the properties from an "elastic" gel to those of a "viscous" liquid. A similar collapse of mucus gel structure was observed after reduction of disulfide bonds in 0.2 M mercaptoethanol, but only after incubation for at least 50 min. This study demonstrates the stability of mucus to several mucosal damaging agents. It is proposed in vivo that although adherent gastroduodenal mucus allows penetration of these agents to the underlying mucosa, it can remain in situ and continue to protect against acid (with HCO3-) and pepsin, thus minimizing mucosal damage and maximizing repair.

Animals↗

Mechanism and dynamics of conformational ordering in xanthan polysaccharide.

The thermally induced order-disorder transition of xanthan (extracellular bacterial polysaccharide from Xanthomonas campestris) has been investigated by optical rotation, differential scanning calorimetry, stopped-flow reaction kinetics and low-angle laser light scattering, and the results have been analysed in terms of Zimm -Bragg helix-coil transition theory. The reciprocal of the transition midpoint temperature (Tm) varies linearly with the logarithm of cation (K+) the salt dependence of Tm, is in agreement with Manning polyelectrolyte theory the ordered structure. The associated increase in cation binding, calculated from the salt dependence of tm, is in agreement with the Manning polyelectrolyte theory for one of the candidate structures from X-ray diffraction, a 5(1) single helix stabilized by packing of side-chains along the polymer backbone, but not for the alternative double-helix structure that has also been proposed. At each salt concentration, the two fundamental parameters of the Zimm -Bragg theory, s and sigma, were calculated. The equilibrium constant for growth of the ordered structure (s) is derived directly from calorimetric measurement of transition enthalpy (delta Hcal ), and sigma, which quantifies the relative instability of the helix nucleus, is derived from the ratio of delta Hcal to the apparent transition enthalpy (delta Happ ) obtained by van't Hoff analysis of the optical rotation data. The temperature course of conformational ordering calculated theoretically is in good quantitative agreement with experimental results from both optical rotation and scanning calorimetry. The calculated average length of stable, ordered chain-sequences increases with decreasing temperature, but equals or exceeds the total chain length from light scattering only at temperatures more than approximately equal to 70 K below Tm, suggesting that ordered and disordered regions may co-exist within the same xanthan molecule. Consistent with this interpretation, the observed rate of conformational ordering increases sharply under conditions where the starting solution for dynamic measurements is partially ordered, suggesting that ordered sequences within each chain may act as helix nuclei for adjacent disordered regions, so that helix growth, rather than the slower nucleation process, becomes rate limiting.

Calorimetry, Differential Scanning↗

An overview of current information on bioavailability of dietary iron to humans.

Bioavailability factors can greatly modify the absorption of dietary iron consumed in different meals by an individual. A greater percentage is generally absorbed of heme iron from animal tissues than of nonheme iron of either animal or plant food. The amount of meat in a meal is the only bioavailability factor known to influence absorption of heme iron. Absorption of iron from the exchangeable nonheme iron pool of a meal is influenced by both enhancing and inhibiting substances or factors. Ascorbic acid, meat, fish, and poultry enhance absorption of nonheme iron, and meals may be classified according to relative bioavailability depending on the content of meat, fish, poultry, and/or ascorbic acid. Some low-molecular-weight organic acids may also increase the bioavailability of nonheme iron. Synthetic metal-chelating agents added to foods and the beverages tea and coffee will inhibit absorption of nonheme iron in a concentration-dependent manner. Wheat bran, soy products, cow's milk, and egg tend to decrease bioavailability of nonheme iron when included in a meal. However, the effect of compounds thought to be responsible for the inhibition in purified form (phytate, fiber, phosphoproteins) is dependent on chemical form and concentration. In some foods there may be as yet unidentified inhibitors or interaction between compounds to inhibit absorption of nonheme iron. Currently available information permits estimation of relative bioavailable iron in a meal.

Ascorbic Acid↗

Zinc: requirements, bioavailabilities and recommended dietary allowances.

This review has approached zinc requirements, bioavailabilities and recommended dietary allowances from a historical view. For example, a requirement for zinc was first demonstrated for the microorganism Aspergillus niger more than a century ago, although zinc has been recognized as a dietary nutrient for humans only within the last decade. Dietary requirement was defined as that quantity of zinc which must be provided daily in order to meet the metabolic requirement. The degree of bioavailability determines the total dietary zinc which must be consumed by humans to remain in metabolic equilibrium. In regard to recommended dietary allowances (RDA), they are recommended average daily intakes of nutrients that population groups should consume. RDA are not synonymous with requirements. Metabolic requirements (the quantity that must be provided to the circulating blood daily) have been determined previously using radio-isotope studies and have indicated a calculated need of approximately 6 mg for an adult per day. More recently a similar amount (4-6 mg) has been found to be required daily (intravenously) in order to maintain plasma zinc concentrations and daily urinary zinc excretion within normal range in hospitalized subjects. Average zinc intakes of large segments of the U.S. population are receiving levels approaching one-half or less the RDA with no apparent deleterious effects. These subjects include pregnant and lactating women. In addition, the zinc content of breast milk is lower than previous studies indicated. Thus, it appears that the majority of breast-fed infants are receiving no more than 70% of the recommended intake, with a recent study indicating less than 50%. Factors reported to affect bioavailability of zinc from foods are discussed. These include fiber and phytate. It was concluded that no definite conclusion can be reached regarding the overall effect of food fiber on zinc balance. Many of the studies were of short duration, with the longest being 32 days. It is probable that different sources of food fiber may have different effects on zinc balance. The apparent discrepancy in the literature regarding the effect of soy protein on zinc requirement was cited. Lastly, the phytate:zinc molar ratio concept was designed to test it as a predictor of zinc bioavailability to humans. The concept must be expanded to recognize the relevance of the total daily dietary zinc intake. Specifically, impairment of absorption of zinc by phytate would be more critical if the total dietary intake was low since the metabolic requirements might not be met.(ABSTRACT TRUNCATED AT 400 WORDS)

Child↗