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A D Bain

Publications and source records attributed to A D Bain.

At least 19 recordsLinked to original sources
PubMed1998

Blurring the distinction between slow and intermediate chemical exchange.

NMR is a vital tool for measuring the dynamics of biological macromolecules in solution. The chemical exchange observed is often divided into slow or intermediate exchange. Slow exchange affects principally the z magnetizations of the system and is observed in modified spin-lattice relaxation experiments. Intermediate exchange gives rise to broadening and coalescence in the spectrum itself. This broadened spectrum is often considered as a whole, but we have shown that it is better to regard it as a sum of transitions, with a generalized picture of the transition probability. In this paper, we give explicit expressions for the lineshape for two sites and review some of the recent applications of chemical exchange in biochemical NMR.

Macromolecular Substances↗
PubMed1993

Conformational studies on calcium binding by tBoc-Leu-Pro-Tyr-Ala-NHCH3, a tyrosine kinase substrate, in a nonpolar solvent.

With a view to understanding the structural requirement for tyrosine phosphorylation, we have examined the free and Ca(2+)-bound conformations of the synthetic peptide tBoc-Leu-Pro-Tyr-Ala-NHCH3, a substrate for a protein tyrosine kinase, using circular dichroism (CD), 1H and 13C nuclear magnetic resonance (NMR) and molecular modeling methods. CD spectrum of the free peptide in water showed a random coil structure, while the spectrum in acetonitrile was indicative of a folded structure containing a type III beta-turn. Dihedral angle data derived from JNH-CH coupling constants, as well as two-dimensional 1H-COSY and NOESY spectral analyses, showed that the peptide adopts a conformation close to the 3(10)-helix. Ca2+ binding by the peptide, as monitored by CD spectral changes, was quite weak in water. However, substantial CD spectral changes were observed in the peptide on addition of Ca2+ in acetonitrile suggestive of major conformational alterations due to Ca2+ binding. Analysis of the binding isotherms at 25 degrees C obtained from CD data in acetonitrile indicated a 2:1 peptide:Ca2+ ("sandwich") complex to be the dominant species with a Kd of about 30 microM. A 1:1 complex was also present and became significant at Ca2+:peptide ratios above 1. By comparison, the peptide formed a predominantly 1:1 complex with Mg2+ with a Kd of about 40 microM. 13C-NMR data showed that a mixture of cis and trans conformers (arising from rotation around the Leu-Pro bond) in the free peptide changes over to the all-trans form on coordination of the peptide carbonyl groups to the Ca2+ ion. 1H-NOESY data of the Ca2+ complex revealed several interactions involving the sidechains of two peptide molecules in the sandwich. Molecular modeling and energy minimization with and without the input of NOESY-derived distance constraints showed the sandwich complex to be an energetically very favourable conformation. Besides its relevance in terms of the possible involvement of divalent cations in substrate-tyrosine kinase interaction, the conformational characterization of tBoc-Leu-Pro-Tyr-Ala-NHCH3 and its Ca2+ complex should help understand the conformational determinants for Ca(2+)-binding by linear peptides.

Amino Acid Sequence↗
PubMed1987

Sudden infant death syndrome in south east Scotland.

Three hundred and fifty eight infants from south east Scotland who died suddenly were classified into four groups. Categories for these groups ranged from where a definite cause of death had been recorded to where no explanation had been provided and no associated disorder was discovered (SIDS). Our results supported the view that there are few differences in the history of cases certified as SIDS and other cases reported as dying suddenly but with an explanation. Groups that most closely matched the SIDS definition employed were reported to be healthier throughout life and freer from illness in the 48 hours before death. From the findings of this study the 'true' SIDS group did not appear as an 'at risk' population. The study group as a whole was not marked by social deprivation, poor mothering, or less privileged families. The importance of intensive investigation, including postmortem examination was emphasised, as misdiagnosis may give a 'falsely' inflated picture of the incidence of the syndrome and could cause unnecessary anxiety.

Birth Order↗
PubMed1985

The human glutathione S-transferases: developmental aspects of the GST1, GST2, and GST3 loci.

The expression of the GST1, GST2, and GST3 loci in fetal, neonatal, and infant tissues has been studied using starch gel electrophoresis and chromatofocusing. Each locus demonstrated developmental changes in expression, some of which were specific to a single tissue while others occurred in several tissues. GST1 was not usually expressed in any of the tissues studied before 30 weeks of gestation but steadily increased thereafter until adult levels were reached in late infancy. In neonates and older infants the frequencies of the GST1*0, GST1*1, and GST1*2 alleles were 0.79, 0.07, and 0.14, respectively. GST2 was always expressed in liver and adrenal but was only weakly expressed in spleen, cardiac muscle, and diaphragm. In kidney this locus was not usually expressed until nearly 1 year after birth. The GST3 isoenzymes were present in all fetal, neonatal, and infant tissues, although their expression in liver decreased after 30 weeks of gestation. Other isoenzymes with fast anodal mobilities were also identified in several tissues; these are believed to be GST3 isoenzymes that have undergone posttranslational modification rather than products of the putative GST4 locus. No specifically fetal isoenzymes were detected.

Chromatography↗
PubMed1984

Chromosome variation in perinatal mortality: a survey of 500 cases.

The results of chromosome analyses on 500 cases of perinatal deaths are reported. It was found that 4.8% were chromosomally abnormal, but 90% of the chromosomally abnormal were either clinically malformed or macerated fetuses. Of the macerated fetuses, 9% were chromosomally abnormal and of these 33% had trisomy 21. The data suggest that the high loss of trisomy 21 fetuses in later stages of pregnancy is of an order sufficient to explain the discrepancy between the higher numbers of trisomy 21 detected during amniotic fluid sampling than found at birth in women of 35 years and over.

Adolescent↗
PubMed1983

Correlation of lysosomal enzyme abnormalities in various forms of adult leukaemia.

Lysosomal enzyme activities were studied in cells derived from the following types of leukaemia: chronic myeloid, acute myeloid, acute myelomonocytic, acute monocytic, non-T, non-B cell acute lymphoblastic, T-cell acute lymphoblastic, B-cell chronic lymphocytic and T-cell chronic lymphocytic. Activities of beta-hexosaminidase and alpha-mannosidase were significantly higher in cells from acute monocytic and acute myelomonocytic leukaemias, and somewhat higher in the other myeloid leukaemias, when compared with control granulocytes. Activities of beta-hexosaminidase, alpha-mannosidase, alpha-fucosidase, beta-glucuronidase and acid phosphatase were markedly lower in B cells of chronic lymphocytic leukaemia when compared with control or other leukaemic lymphoid cells. On isoelectric focusing abnormal patterns of beta-hexosaminidase, alpha-mannosidase and beta-glucuronidase activities were commonly found in myeloid and non-T, non-B cell leukaemias. All patients with acute myeloid leukaemia exhibited a relative decrease in the B form of beta-hexosaminidase activity. The results described show that studies on lysosomal enzymes may assist in the classification of different types of leukaemia.

Adult↗
PubMed1982

Elucidation of an unbalanced chromosome translocation by gene dosage studies.

A chromosome abnormality, 46,XY,1p+, was detected in cultured amniotic fluid cells. The chromosomes of both parents were normal and it was impossible to recognise the extra chromosomal material using current banding techniques. The activity of acid alpha-glucosidase was found to be consistently higher than controls whereas activity of several other lysosomal enzymes, galactokinase and thymidine kinase was not. The results suggest that the extra material is that part of the long arm of chromosome 17 bearing the gene for acid alpha-glucosidase but not the genes for galactokinase and thymidine kinase. This would narrow the assignment of the acid alpha-glucosidase locus to 17q22 leads to 17 qter.

Cells, Cultured↗
PubMed1978

Use of a chromogenic substrate for the diagnosis of Krabbe's disease, with special reference to its application in prenatal diagnosis.

A chromogenic substrate, 2-hexadecanoylamino-4-nitrophenyl-beta-D-galactopyranoside, has recently been described for the diagnosis of Krabbe's disease. Hydrolysis of this substrate by extracts of cultured cells and tissues was compared with the activities of lactocerebrosidase I and non-specific beta-galactosidase. Under appropriate conditions, hydrolysis of the chromogenic analogue was markedly reduced in extracts of cultured amniotic fluid cells and skin fibroblasts derived from cases of Krabbe's disease. Activity was also markedly deficient in extracts of Krabbe's brain, although only a partial reduction was measured in liver extracts. Generally activities were higher in tissues of fetal origion. Unfortunately, the new analogue proved less specific and less sensitive than the natural substrates used to diagnose Krabbe's disease. Consequently, the analogue does not provide a satisfactory alternative substrate for the prenatal diagnosis of Krabbe's disease.

Adolescent↗
PubMed1978

Krabbe's disease in an infant and her fetal sibling. A case report.

Degenerative diseases of the cerebral white matter are rare, but have severe consequences. The diagnosis of one such disorder, Krabbe's disease, may be made by biochemical analysis of cultured fibroblasts. As the disease is inherited as an autosomal recessive trait, there is a high risk of affected children being born to a heterozygote couple. A description is given of an infant with Krabbe's disease and of the monitoring of the mother's second pregnancy in which an affected fetus was found.

Amniotic Fluid↗
PubMed1978

Chromosome studies at the paediatric necropsy.

The results of chromosome studies from 1193 consecutive paediatric necropsies in Edinburgh and 331 in Adelaide are given. In the Edinburgh series 51 major chromosome abnormalities were detected in 780 (6.5%) necropsies where chromosome studies were successful and in Adelaide 16 in 295 (5.4%) were found. It is suggested that chromosome studies should become an integral part of the paediatric necropsy except for deaths due to primary central nervous system lesions and trauma.

Australia↗