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Biomedical subjects

M G Kelly

Publications and source records attributed to M G Kelly.

At least 19 recordsLinked to original sources
PubMed2001

Use of similarity measures for quality control of benthic diatom samples.

A method for evaluating the similarity of replicate benthic diatom samples based on the Bray-Curtis similarity measure is described. This technique may be useful as part of quality control procedures where objective performance measures are required. Levels of similarity > 60% typically indicate good agreement between the primary analyst and auditor. However, an evaluation of 57 comparisons indicated that achievable levels of similarity were dependent upon the species diversity of the sample, with samples with high species diversity typically having lower levels of similarity than samples with low species diversity. Whilst a threshold value of 60% is adequate for most samples, a stiffer threshold of 70% should be applied to samples with very low levels of diversity.

Diatoms↗
PubMed2000

Directional selection on initial flowering date in Phlox drummondii (Polemoniaceae).

The fitness effects due to initial flowering date in Phlox drummondii were determined for three populations in central Texas (USA) over 3 yr (1990-1992). Mean fitness (seed set) always decreased with the later initiation of flowering. The likelihood of a plant fruiting differed with flowering date in five of the six instances (population by year combinations). Though plants that initiated flowering later tended to have spent more time in the vegetative stage and tended to die later in the year than did earlier flowering plants, this was not sufficient to overcome the reproductive penalties of flowering late. Plants that initiated flowering later in the season spent less time in the adult phase and were smaller. The mean number of flowers, fruits, and seeds per flowering plant always decreased with later flowering. Fruit set was negatively correlated with flowering date in four of the six population by year combinations. Nonparametric fitness functions were used to summarize predicted fitness among different initial flowering dates for each population on a yearly basis. Predicted mean fitness always declined nonlinearly with later flowering; the earliest flowering plants always had the highest predicted fitness. These fitness functions describe directional selection for the early initiation of flowering.

Journal Article↗
PubMed1997

Rapid assessment of onchocerciasis prevalence and a model for selecting communities for ivermectin distribution in West Africa.

Analysis of the prevalence of onchocerciasis in an area of north-east Nigeria indicates that clinical symptoms are generally good predictors of the rate of onchocerciasis infection and of the mean microfilarial density in infected individuals. However, differences between regions and anomalous communities within regions make reliance on a single indicator dubious. Use of multivariate equations was tested, but offered little improvement over bivariate ones and an algorithmic approach, making use of local knowledge of factors which might complicate interpretation, is proposed instead. The framework is suggested as a basis for screening, although a larger database is required to produce definitive equations.

Algorithms↗
PubMed1996

Synthesis of Hexahydrocyclopentimidazol-2-(1H)-one derivatives displaying selective DP-receptor agonist properties.

The rationale for investigating conformationally restricted analogues of BW245C as DP-receptor ligands and the syntheses of three such racemic bicyclic imidazolidinone analogues are described. Compounds 7 (BW587C), 8 (BW480C85), and 9 (BW572C85) were found to be potent inhibitors of human platelet aggregation and selective DP-receptor agonists in washed platelet and jugular vein isolated tissue assays.

Animals↗
PubMed1996

The carboxyl terminus of myosin binding protein C (MyBP-C, C-protein) specifies incorporation into the A-band of striated muscle.

Myosin binding protein-C (MyBP-C), also known as C-protein, is a major constituent of the thick filaments of vertebrate striated muscles. The protein, approximately 130 kDa, consists of a series of 10 globular motifs (numbered I to X) each of approximately 90-100 amino acids, bearing resemblance to the C2-set of immunoglobins (Ig C2) and to the fibronectin type III (FnIII) motifs. Using pure preparations of myosin and MyBP-C, it has been demonstrated that the major myosin binding domain of MyBP-C resides within the C-terminal Ig C2 motif (motif X). However, in the context of the in vivo thick filament, it is uncertain if the latter domain is sufficient to target MyBP-C correctly to the A-band or if other regions of the molecule are required for this process. To answer this question, cultures of skeletal muscle myoblasts were transfected with expression plasmids encoding seven truncation mutants of MyBP-C, and their targeting to the A-band investigated by immunofluorescence microscopy. To distinguish the recombinant proteins from endogenous MyBP-C, a myc epitope was inserted at each amino terminus. Recombinant MyBP-C exhibited an identical distribution in the sarcomere to that of native MyBP-C; i.e. it was found exclusively in the C-zone of the A-band. A mutant encoding the C-terminal 372 amino acids, but lacking motifs I-VI (termed delta 1-6), also targeted correctly to the A-band. This fragment, which is composed of two Ig C2 and two FnIII motifs, was the minimal protein fragment required for correct A-band incorporation. Larger amino-terminal deletions or deletion of motif X, the myosin binding domain, abolished all localization to the A-band. One construct (delta 10) lacking only motif X strongly inhibited myofibril assembly. We conclude that the myosin binding domain of MyBP-C, although essential, is not sufficient for correct incorporation into the A-band and that motifs VII to IX are required for this process. The data suggest a topological model in which MyBP-C is associated with the thick filament through its C terminus.

Animals↗
PubMed1989

The classification of prostaglandin DP-receptors in platelets and vasculature using BW A868C, a novel, selective and potent competitive antagonist.

1. BW A868C, a novel compound, behaved as a simple competitive antagonist in a human washed platelet aggregation assay. Anti-aggregatory concentration-effect curves to BW 245C were displaced in a parallel manner. The shifts accorded with a Schild plot slope of unity and a pKB of 9.26. 2. Inhibition of platelet aggregation by prostaglandin D2 (PGD2) was antagonized with a similar potency, as were the relaxation effects of BW 245C and PGD2 in the rabbit jugular vein. BW A868C can, therefore, be classified as a DP-receptor antagonist. 3. Actions of BW A868C at other prostaglandin receptors (IP, EP1, EP2, TP and FP) were excluded at concentrations up to 1,000 times higher than the DP-receptor affinity. 4. Analyses of BW 245C- and PGD2-mediated effects were complicated by additional agonist receptor interactions which were revealed by BW A868C. In rabbit jugular vein a resistant phase of agonism was detectable, indicating that both agonists exerted effects through another receptor (possibly EP2). Also, PGD2, in addition to its anti-aggregatory effect on platelets, demonstrated a pro-aggregatory action in the presence of BW A868C. 5. The contractile effects of PGD2 in guinea-pig tracheal strips were resistant to 10 microM BW A868C indicating that they were not mediated through DP-receptors. 6. To our knowledge this is the first account of a well-classified competitive antagonist at the DP-receptor. Its potency and selectivity make it an important new tool in prostanoid receptor classification and identification.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1989

The antagonism by BW A868C of PGD2 and BW245C activation of human platelet adenylate cyclase.

1. In glycerol-lysed human platelets, prostaglandin D2 (PGD2) and the hydantoin BW245C both activate adenylate cyclase in a biphasic manner. These activations are qualitatively different from those of carbacyclin, iloprost and prostaglandin E2 (PGE2) whose E/[A] curves can be adequately described by rectangular hyperbolae. 2. Prostaglandin E1 (PGE1) had E/[A] curves of slope significantly lower than that expected for a rectangular hyperbolae. 2. Prostaglandin E1 (PGE1) had E/[A] curves of slope significantly lower than that expected for a rectangular hyperbola. 3. The selective PGD2 antagonist BW A868C shifts the first phase of the PGD2 and BW245C E/[A] curves but has no effect on the second phase. 4. Applying a two-receptor model enables a pKB to be derived for BW A868C of 9.11. 5. BW A868C has no effect on carbacyclin, iloprost, prostacyclin, PGE1 and PGE2 at a concentration 1,000 fold that of its KB against PGD2 and BW245C. 6. These results indicate that PGD2 and BW245C are capable of activating adenylate cyclase in human platelets through the DP-receptor and by another mechanism as yet uncharacterized.

Adenylyl Cyclases↗
PubMed1988

Development and evaluation of an enzyme inhibition assay for methotrexate.

A method for the measurement of methotrexate based on its inhibition of dihydrofolate reductase (EC 1.5.1.3) is described. The performance of the method is evaluated and a brief assessment of its clinical usefulness made. Reaction time, pH, and the relative concentration of enzyme and inhibitor all have a significant effect on the shape of the standard curve. Pre-incubation of enzyme with methotrexate resulted in increased inhibition, but did not improve the sensitivity or linearity of the assay. Data are presented on the imprecision, specificity and accuracy of the method. The method is simple to perform, rapid and inexpensive. The sensitivity and specificity of the method are such as to allow for effective monitoring of patients on methotrexate therapy.

Animals↗
PubMed1988

Post accident/incident counseling: some exploratory findings.

An examination of the literature, and other sources of information, suggested that there might be prophylactic value in early psychological intervention following crewmember involvement in stressful incidents. An exploratory study, at a small commercial pilot base (c.200 pilots), was undertaken to assess the value of early intervention. Pilots were automatically referred to an independent counseling service if abnormal flight events were judged to have involved sudden, unanticipated, or extreme stress. While some individuals came through their experience relatively unaffected, a surprising proportion did not. Several individuals took the opportunity to voluntarily return for additional counseling while others required anxiolytic drug treatment. The initial findings of this exploratory study strongly suggest that commercial pilots are more frequently subject to a potentially debilitating stress reaction than heretofore suspected. This has obvious implications for intervention and prevention, as well as long-term stress management for commercial pilots.

Accidents, Aviation↗