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Biomedical subjects

J Wilkie

Publications and source records attributed to J Wilkie.

At least 19 recordsLinked to original sources
PubMed2001

NMR studies and semi-empirical energy calculations for cyclic ADP-ribose.

A possible pH-dependent conformational switch was investigated for cyclic ADP-ribose. NMR signals for the exchangeable protons were observed in H2O at low temperature, but there was no direct evidence for the protonation of N-3 at neutral pH that has previously been postulated. MNDO calculations indicated that pH dependent 31P chemical shift changes are attributable to protonation of the phosphate adjacent to the N-1 of adenine, and not due to trans-annular hydrogen bonding with a protonated N-3.

Adenosine Diphosphate Ribose↗
PubMed2000

The 6-OH group of D-inositol 1-phosphate serves as an H-bond donor in the catalytic hydrolysis of the phosphate ester by inositol monophosphatase.

Inositol monophosphatase plays a pivotal role in the biosynthesis of secondary messengers and is believed to be a target for lithium therapy. It is established how a lithium ion works in inhibiting the enzyme but details of the mechanism for the direct magnesium ion activated hydrolysis of the substrate have been elusive. It is known that substrates require a minimal 1,2-diol phosphate structural motif, which in D-myo-inositol 1-phosphate relates to the fragment comprising the 1-phosphate ester and the 6-hydroxy group. Here it is shown that inhibitors that are D-myo-inositol 1-phosphate substrate analogues possessing 6-substituents larger than the 6-hydroxy group of the substrate, for example, the 6-O-methyl analogue, are able to bind to the enzyme in a congruous manner to the substrate. It is demonstrated, however, that such compounds show no substrate activity whatsoever. It is also shown that a 6-amino group is able to fulfil the role of the 6-hydroxy group of the substrate in conferring substrate activity and that a 6-methylamino group is similarly able to support catalysis. The results indicate that a 6-substituent capable of serving as a hydrogen-bond donor is required in the catalytic mechanism for hydrolysis. It has recently been shown that inositol is displaced from phosphorus with inversion of stereochemistry and we expect that the nucleophilic species is associated with Mg(2+)-1. It is proposed here that the role of the 6-hydroxy group of the substrate is to H-bond with a water molecule or hydroxide ion located on Mg(2+)-2. From this analysis, it appears that the water molecule bound to Mg(2+)-2 serves as a proton donor for the inositolate leaving group in a process that stabilises the alkoxide product and retards the back-reaction.

Animals↗
PubMed2000

Positivity preserving non-markovian master equations

A general class of integrodifferential non-Markovian master equations is developed which is representative of the dynamics of small subsystems interacting with open reservoirs with memory. Conditions which guarantee positivity of the subsystem reduced density are established.

Journal Article↗
PubMed1997

The effect of discharge pack formula and breast pumps on breastfeeding duration and choice of infant feeding method.

BACKGROUND: A study of breastfeeding mothers was conducted from October 1993 through July 1994 in the western United States to determine the influence of components of hospital discharge packs on the duration of breastfeeding. METHOD: On discharge from the hospital, over 1600 breastfeeding mothers were given one of four free discharge packs, identical in all ways except that one contained a can of powdered formula, one a manual breast pump, one both formula and pump, and one neither. During the following 6 months, mothers were interviewed by telephone three times by an independent research firm to determine how and what they were feeding their infants. Analysis of the independent and interactive effects of both formula and pump was performed, and the moderating effects of age, ethnicity, marital and insurance status, prebirth feeding plan, and the effect of returning to outside employment or school were examined. RESULTS: Across the entire sample, the contents of the discharge packs had a negligible effect on feeding method and breastfeeding duration. Examination of select subgroups revealed modest discharge pack effects, wherein the presence of discharge pack formula increased the likelihoof2p4 introducing supplementation during the first 6 weeks whereas receipt of pumps prolonged full breastfeeding. Even in these select groups, however, no effect was observed on the overall duration of breastfeeding. CONCLUSION: Relative to other known influences on the choice of feeding method and on breastfeeding duration, discharge pack contents do not merit great concern.

Adult↗
PubMed1995

Results of a prospective randomized trial using DTIC and interferon as adjuvant therapy for stage I malignant melanoma.

This prospective randomized trial evaluated the effect of DTIC and interferon as adjuvant therapy for high risk stage 1 malignant melanoma in 26 patients. Both groups were well matched for depth of disease, site of melanoma and other prognostic criteria. Like other studies the findings of 2.6 times increased relative risk of mortality in the treatment arm do not support a rationale for adjuvant immuno-chemotherapy even in patients at high risk of recurrence.

Adult↗
PubMed1989

The conformations and electrostatic potential maps of phorbol esters, teleocidins and ingenols.

Phorbol esters and the structurally dissimilar teleocidins and ingenols bind to and activate protein kinase C (PKC) during the course of tumour promotion. These compounds are referred to as TPA-like tumour promoters (from 12-O-tetradencanoyl phorbol-13-acetate, the most active of the class) and are amongst the most potent tumour promoters known. Despite their structural dissimilarity, all three groups of molecules have been shown to bind to the diacylglycerol site of PKC with high affinity. It is thought that this binding to and consequent activation of PKC is the crucial step in tumour promotion by these compounds. The aim of this work was to provide a description of the binding site by comparing structural features (in particular the electrostatic potential) with the activity of numerous derivatives of the three classes. Initially the description was obtained by consideration of the phorbol derivatives, and then refined using the teleocidins and ingenols. The activity data were collected from a variety of sources and the structures calculated using the semi-empirical MNDO approximation embodied in the MOPAC program. Where possible, the crystal structure was obtained from the Cambridge Crystallographic Database, and used as a starting point for the calculation. In other cases, a preliminary calculation was carried out using the molecular mechanics program AMBER. Electrostatic potentials were calculated and displayed using an in-house program 3D2, while superpositions of molecules were carried out using CHEM-X.

Diterpenes↗
PubMed1973

Inactivation of Herpesvirus hominis types 1 and 2 by silver nitrate in vitro and in vivo.

Herpes simplex virus (HSV) types 1 and 2 (two strains each) were inactivated at different rates in vitro by 40 muM AgNO(3). The inactivation of HSV type 1 strains was virtually complete in 10 to 15 min, whereas almost half of the infectivity of HSV type 2 strains survived this exposure. One strain of type 1 inoculated into rabbit eyes was almost completely inactivated by 1% AgNO(3) solution dropped into the eye 20 min later, so that there was markedly reduced viral replication and less corneal herpetic disease. One strain of HSV type 2 in the rabbit eye was not effectively inactivated by 1% AgNO(3). From these results, it seems likely that AgNO(3) instillation into the eyes of a newborn who has passed through a birth canal infected with HSV might prevent eye infection with HSV type 1 but not with type 2. The greater resistance of HSV type 2 strains to chemical inactivation in vitro and in vivo may be of medical concern.

Animals↗