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Biomedical subjects

M A Khaled

Publications and source records attributed to M A Khaled.

At least 19 recordsLinked to original sources
PubMed1995

Comparison of the modified relative dose response (MRDR) and the relative dose response (RDR) in the assessment of vitamin A status in malnourished children.

The modified-relative-dose-response (MRDR) test and the relative-dose-response (RDR) test were compared in 49 mildly to moderately malnourished Bangladeshi children. The MRDR test had a significantly lower sensitivity, detecting only 71% of children with very low serum retinol (< or = 0.35 mumol/L) and 33% of children with low serum retinol (0.355-0.70 mumol/L) compared with 100% and 80% for the RDR test, respectively. The MRDR test showed a very strong dependency on retinol-binding protein (RBP) saturation (ie, percent saturation of RBP with retinol) compared with the RDR test. Only 3 (23%) of 13 children with RBP saturation > or = 55% but low vitamin A stores were diagnosed as abnormal by the MRDR test. This suggests that when apo-RBP concentration is limiting, as it is in malnourished children, didehydroretinol, the analog used in the MRDR test cannot effectively compete with retinol for binding to apo-RBP. Under these circumstances, the MRDR test is rendered ineffective. The possibility of increasing the sensitivity of the test by using a high dose of didehydroretinol needs to be investigated.

Child, Preschool↗
PubMed1995

Conjunctival impression cytology fails to detect subclinical vitamin A deficiency in young children.

Thirty-four asymptomatic children, ages 5-35 mo, were studied to compare the conjunctival impression cytology technique with the relative dose response test in detection of subclinical vitamin A deficiency. Conjunctival smears were collected from the infero-temporal-bulbar conjunctiva of each eye with a strip of cellulose acetate filter paper and transferred onto a glass slide. Venous blood was drawn at 0 and 5 h after administration of an oral dose of 1000 micrograms of retinol palmitate (relative dose response test). An increase in serum retinol concentration (> or = 20%) in the 5-h value was considered indicative of an inadequate liver store of vitamin A and hence subclinical vitamin A deficiency. Of the 34 children, 26 (76.5%) had moderate to severe protein-energy malnutrition. Only three children (9%) had abnormal conjunctival impression cytology, whereas 23 (68%) had abnormal relative dose response. Even more striking was the finding that only two of the 23 children with abnormal relative dose response had abnormal conjunctival impression cytology. The results suggest that the conjunctival impression cytology test has poor agreement with the relative dose response test results in assessing vitamin A status in young children. If relative dose response is considered an acceptable reference method for assessing vitamin A status, then the conjunctival impression cytology test cannot be considered a valid measure of subclinical vitamin A deficiency in this population.

Bangladesh↗
PubMed1992

Estimation of computerized tomography derived abdominal fat distribution.

Measurements of intra-abdominal fat (IAF) may be important since it is associated with numerous metabolic disorders. The relationship between computerized tomography (CT) measured fat distribution and densitometry measures was investigated in a sample of 61 male Caucasian subjects, aged 18 to 30 years with varying adiposity. Regression models were developed for estimating CT-derived fat of 40 men to estimate IAF. Two equations were developed to estimate IAF. The first used only anthropometric measures. Waist circumference and log chest ratio entered the equation and accounted for 67% of the variance. The second model included densitometry-measured percentage fat with the centred product of waist and hip circumferences, accounting for 73% of the variance. Regression equations were also developed to estimate subcutaneous fat area so that the ratio of IAF to subcutaneous fat might be estimated. Although subcutaneous fat could be estimated, the ratio between IAF and subcutaneous fat could not be estimated accurately. A validation of all regression equations developed for male subjects who also completed using a separate validation sample (n = 21). Only the studies with sample characteristics similar to those found in the validation sample validated satisfactorily. Results indicate that anthropometric and densitometry measures cannot be used to estimate CT-derived abdominal fat with precision, however they may be of value in health risk screening of individuals with high levels of IAF. Proper selection procedures with regard to age, adiposity, and morbidity must be used.

Adipose Tissue↗
PubMed1987

Determination of total body water by deuterium NMR.

A new deuterium nuclear magnetic resonance (2H NMR) method is described for determining total body water in humans. The method has been validated against a standard infrared absorption (IR) procedure using a tracer dose of deuterium oxide (2H2O) of approximately 10 g for each human subject. The precision and accuracy for the methods have been compared and found to be very similar. The advantages of the 2H NMR method over other presently available techniques that are based on 2H2O dilution are as follows: it is fast, accurate, needs only a small dose of 2H2O, can be done using any body fluid, and, most importantly, does not require any sample preparation.

Adult↗
PubMed1985

Association of folate molecules as determined by proton NMR: implications on enzyme binding.

The self-association in aqueous solution of folic acid (FA), 7,8-dihydrofolic acid (DHFA) and 5,6,7,8-tetrahydrofolic acid (THFA) has been studied by the use of proton magnetic resonance (1H NMR) spectroscopy. At concentrations below 10 mM, all three folates exist in (monomer)2 in equilibrium dimer equilibria with association constants (Ka) equal to 400, 66 and 14 M-1 for FA, DHFA and THFA respectively. These values decreased markedly to 157, 18 and 3 M-1, for FA, DHFA and THFA respectively, in the presence of 0.8 M KCl. The high extent of dimerization of FA is believed to impede the interaction with the active site of dihydrofolate reductase (DHFR) rendering it a poor substrate. In contrast, the DHFA with a much lower Ka is a better substrate. Conditions that lower the Ka of both FA and DHFA, (i.e., 0.8M KCl) turn them into better substrates. Based on the findings of the present study, it is also predicted that dihydro MTX may be a better inhibitor of DHFR than MTX.

Chemical Phenomena↗
PubMed1984

The case for the anticode.

The present paper will focus on the developments in our lab related to the origin of the code since the Israel meeting (1,2). Principally these items are: (a) a new set of correlations (3) which include ranked hydrophobicities of amino acids and dinucleotides; (b) binding constants (4) of Phe for the four mononucleotides; and (c) binding constants (5) of Phe, Leu, Ile, Val, and Gly for polyadenylic acid (poly A). The data continue to support a model for the origin of the code based on relationships between amino acids and their anticodons.

Amino Acids↗
PubMed1984

Binding constants of phenylalanine for the four mononucleotides.

Earlier work has shown that several properties of amino acids correlate directly with properties of their anticodonic nucleotides. Furthermore, in precipitation studies with thermal proteinoids and homopolyribonucleotides, an anticodonic preference was displayed between Lys-rich, Pro-rich and Gly-rich thermal proteinoids and their anticodonic polyribonucleotides. However, Phe-rich thermal proteinoid displayed a preference for its codonic nucleotide, poly U. This inconsistency seemed to be explained by a folding in of the hydrophobic residues of Phe causing the proteinoid to appear more hydrophilic. The present work used nuclear magnetic resonance techniques to resolve a limited question: To which of the four nucleotides does Phe bind most strongly? The results show quite clearly that Phe binds most strongly to its anticodonic nucleotide, AMP.

Adenosine Monophosphate↗
PubMed1983

Complexes of polyadenylic acid and the methyl esters of amino acids.

This report includes studies of the binding of the methyl esters of a series of amino acids to polyadenylic acid. The principal data were obtained using proton NMR; however, some additional data were obtained through the study of insoluble complexes and through ultraviolet spectroscopy. The binding constants are in the order Phe greater than Ile greater than or equal to Leu greater than Val greater than Gly, and show a direct correlation with the hydrophobicities of the amino acids. In most cases they are essentially double the binding constants found by Reuben and Polk (1980) for monomeric AMP. All of these amino acids, except Gly, have A as the middle letter of their anticodons, and Phe is the only one with XAA as its only anticodon. It has the anticodon richest in A and has the highest binding constant for A. These results, coupled with other data, continue to support a model of the origin of the code which is based on weak, but selective affinities between amino acids and their anticodons.

Amino Acids↗
PubMed1982

Solution and ion-complexed conformations of beauvericin determined by proton magnetic resonance spectroscopy.

The conformational properties of the cyclohexadepsipeptide antibiotic Beauvericin have been investigated by 1H-NMR spectroscopy in polar (C2H3O2H) and non-polar (CCl4, C62H6, C2HCl3) solvents and in two solvent mixtures; one a mixture of a polar and non-polar solvent (C2H3O2H/CCl4) and the other an aromatic solvent in a non-polar environment (C62H6/CCl4). The ion-complexation properties of Beauvericin with alkali metal halides (Li+, Na+, K+, Cs+) have also been studied. It is demonstrated that changes in chemical shifts of Beauvericin with concentration, with polarity of solvent or with added alkali metal ion reflect changes not only in the solvent properties but also changes in backbone conformation and changes due to ion-complexation, where appropriate, and therefore cannot be used, by themselves, to determine the conformation of the molecule, its self-aggregation properties, or the stoichiometry of the metal ion-complex. The backbone conformations of Beauvericin in different environments are determined by methods that are independent of chemical shift analysis; i.e., by measurements of 5J(HH) magnitudes observed between the alpha-CH protons of the L-phenylalanine and D-hydroxyisovaleric acid (DHyIv) residues and by nuclear Overhauser effect measurements observed between alpha-CH(HyIv) and (N)-CH3(Phe) proton signals. In the knowledge of these results the chemical shifts of Beauvericin in different environments can then be rationalised. It is found that the conformation of Beauvericin in a polar solvent is different from that found in a non-polar solvent and from that found for the in the ion-complexed form is similar to that found in non-polar solvents. By taking into account the conformational properties of the L-phenylalanine and DHyIv side-chains, it is possible to assign unambiguously the magnetically non-equivalent beta-CH2(Phe) and gamma Me(HyIv) proton signals and so elucidate the complete conformational behaviour of the uncomplexed forms of Beauvericin in a polar and a non-polar environment, and of the ion-complexed form of Beauvericin in a polar solvent.

Anti-Bacterial Agents↗
PubMed1981

Conformation characterization of cyclopentapeptide, L.Val-L.Pro-Gly-L.Val-Gly: a repeating analogue of elastin.

The cyclopentapeptide, L.Val1-L.Pro2-Gly3-L.Val4-Gly5, was synthesized and its conformational characterization was carried out using n.m.r. and theoretical energy calculations. The n.m.r. studies indicated the existence of a cis Val1-Pro2 peptide bond in water and a very strong intramolecular H-bond between the val1 NH and Gly3 C=O groups. This H-bond forms a beta-turn (type II) placing Val4 and Gly5 residues within the turn. Two minimum energy conformations were derived, one of which agrees very well with the solution conformation.

Amino Acid Sequence↗
PubMed1980

15N-NMR of repeat peptides of tropoelastin. The tetrapeptide.

The 15N-NMR data obtained in chloroform and methanol are reported for Boc-L-Val1-L-Pro2-Gly3-Gly4-OMe, a repeat tetrapeptide sequence of tropoelastin. Deuterium substitution for labile peptide protons was carried out to delineate solvent-exposed and solvent-shielded peptide nitrogens. Solvent perturbation of the peptide nitrogen resonances together with the hydrogen-deuterium substitution reaffirms the previously derived conformation of the molecule in chloroform which contains a beta-turn (type II) and a 14-membered hydrogen bond to form a cross-beta structure.

Chloroform↗
PubMed1980

Rate theory calculation of gramicidin single-channel currents using NMR-derived rate constants.

By means of 23Na NMR, two ion binding sites were observed in phospholipid-packaged gramicidin channels and the four associated rate constants were approximated. Limits also were placed on a fifth rate constant for an intrachannel ion translocation. By using Eyring rate theory to introduce voltage dependence, these rate constants were used in steady-state-current equations for calculation of gramicidin single-channel currents for two- and three-site models. Calculated single-channel currents are compared with previously published experimental single-channel currents obtained by electrical measurements on Na+ transport across gramicidin-doped planar lipid bilayers. The calculated results for the two- and three-site models compare favorably with the experimental results. Accordingly, it is demonstrated that NMR-derived rate constants can be coupled with Eyring rate theory to calculate currents through a transmembrane channel and to do so within levels of variation that compare with the differences obtained on planar lipid bilayers formed with different lipids.

Binding Sites↗
PubMed1979

Nuclear magnetic resonance studies on a cyclic dodecapeptide analogue of a repeat hexapeptide of tropoelastin: evaluation of secondary structure.

The cyclododecapeptide, (Ala1-Pro2-Gly3-Val4-Gly5-Val6)2, was synthesized and its secondary structure was evaluated from extensive studies in dimethyl sulphoxide, trifluoroethanol and water using NMR methods. A selective decoupling technique in 13C-NMR has been utilized in order to assign the C=O carbon resonances. Temperature dependence of the peptide NH protons and the solvent perturbation of the peptide NH and C=O resonances show the occurrence in all solvents of a beta-turn (a 10-membered H-bond between the Val4 NH and Ala1 C=O) and a gamma-turn, an 11-membered H-bond between the Gly3 NH and the Gly5 C=O; and a possible 14-membered H-bond between the Ala1 NH and the Val4 C=O in dimethyl sulphoxide and trifluoroethanol. These secondary structural features are compared with the linear polyhexapeptide and found the the beta-turn and the gamma-turn are the common conformational features of these peptide systems.

Amino Acid Sequence↗
PubMed1978

Proton magnetic resonance and conformational energy calculations of repeat peptides of tropoelastin. A permutation of the hexapeptide.

The conformation of a hexapeptide sequence occurring in tropoelastin is discussed from the results obtained using a combined approach of theoretical conformational energy calculations on HCO-Val-Ala-Prb-Gly-OMe and 1h nmr studies on t-Boc-Val-Ala-Pro-Gly-Val-Gly-OMe in a dilute solution of methanol. Both studies have reasonable concurrence with respect to the preferred conformation of the hexapeptide and an analysis of the combined results suggests that the hexapeptide is stabilized by a beta-turn involving the Ala1,iC=O and Val4,iNH groups and a gamma-turn involving Gly5,iC=O and Gly3,iNH groups. A weaker interaction between Gly3,iC=O and Gly5,iNH groups is also found to be possible. Conformational features of the first valyl residue in the sequence Val-Ala-Pro-Gly-Val-Gly and the last valyl residue in Ala-Pro-Gly-Val-Gly-Val are compared and found to have similar torsion angles. The implications of such a similarity are discussed with respect to the conformation of the polyhexapeptide.

Amino Acid Sequence↗