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Biomedical subjects

N Ng

Publications and source records attributed to N Ng.

9 recordsLinked to original sources

High dose-rate brachytherapy source localization: positional resolution using a diamond detector.

A potential real-time source position verification process for high dose-rate (HDR) brachytherapy treatment is described. This process is intended to provide immediate confirmation that a treatment is proceeding according to plan, so that corrective action can be taken if necessary. We show that three dosimeters are in principle sufficient and demonstrate the feasibility of the process using a diamond detector and an Ir-192 source. An error analysis including all identified sources of error shows that this detector is capable of locating the distance to the source to within 2 mm for distances up to 12 cm. This positional accuracy is less than the diameter of typical HDR catheters indicating that a diamond detector can be used to accurately determine the distance to the source. The uncertainty in the distance is found to increase with distance.

Algorithms↗

A genetic analysis of synaptic development: pre- and postsynaptic dCBP control transmitter release at the Drosophila NMJ.

Postsynaptic dCBP (Drosophila homolog of the CREB binding protein) is required for presynaptic functional development. Viable, hypomorphic dCBP mutations have a approximately 50% reduction in presynaptic transmitter release without altering the Ca2+ cooperativity of release or synaptic ultrastructure (total bouton number is increased by 25%-30%). Exogenous expression of dCBP in muscle rescues impaired presynaptic release in the dCBP mutant background, while presynaptic dCBP expression does not. In addition, overexpression experiments indicate that elevated dCBP can also inhibit presynaptic functional development in a manner distinct from the effects of dCBP loss of function. Pre- or postsynaptic overexpression of dCBP (in wild type) reduces presynaptic release. However, we do not observe an increase in bouton number, and presynaptic overexpression impairs short-term facilitation. These data suggest that dCBP participates in a postsynaptic regulatory system that controls functional synaptic development.

Animals↗

Drosophila Futsch regulates synaptic microtubule organization and is necessary for synaptic growth.

We present evidence that Futsch, a novel protein with MAP1B homology, controls synaptic growth at the Drosophila neuromuscularjunction through the regulation of the synaptic microtubule cytoskeleton. Futsch colocalizes with microtubules and identifies cytoskeletal loops that traverse the lateral margin of select synaptic boutons. An apparent rearrangement of microtubule loop architecture occurs during bouton division, and a genetic analysis indicates that Futsch is necessary for this process. futsch mutations disrupt synaptic microtubule organization, reduce bouton number, and increase bouton size. These deficits can be partially rescued by neuronal overexpression of a futsch MAP1B homology domain. Finally, genetic manipulations that increase nerve-terminal branching correlate with increased synaptic microtubule loop formation, and both processes require normal Futsch function. These data suggest a common microtubule-based growth mechanism at the synapse and growth cone.

Animals↗

A sigma32 mutant with a single amino acid change in the highly conserved region 2.2 exhibits reduced core RNA polymerase affinity.

sigma32, the product of the rpoH gene in Escherichia coli, provides promoter specificity by interacting with core RNAP. Amino acid sequence alignment of sigma32 with other sigma factors in the sigma70 family has revealed regions of sequence homology. We have investigated the function of the most highly conserved region, 2.2, using purified products of various rpoH alleles. Core RNAP binding analysis by glycerol gradient sedimentation has revealed reduced core RNAP affinity for one of the mutant sigma32 proteins, Q80R. This reduced core interaction is exacerbated in the presence of sigma70, which competes with sigma32 for binding of core RNAP. When a different but more conserved amino acid was introduced at this position by site-directed mutagenesis (Q80N), this mutant sigma factor still displayed a significant reduction in its core RNAP affinity. Based on these results, we conclude that at least one specific amino acid in region 2.2 is involved in core RNAP interaction.

Amino Acid Sequence↗

Smoking cessation programme: an ethical analysis.

Many midwives feel it is their moral duty to advise and help pregnant smokers to stop smoking Do midwives have the right to persuade or coerce pregnant smokers to stop smoking? Giving information is not sufficient to help clients to make informed choice Smokers need help to acquire necessary skills to raise self-esteem and assertiveness to make informed decisions Many women use smoking as a coping strategy to ensure their own mental well-being and that of their families The majority of women smokers are among the lower socio-economic groups It is essential for midwives to develop strategies that are sensitive and pertinent to the smokers' psychological and socio-economic needs Is it ethical or practical to enforce a total non-smoking policy in a maternity unit? As individuals, pregnant smokers have a 'right' to smoke Pregnant smokers smoke more on admission to hospital Illicit smoking will subject non-smokers to passive smoking and increase incidence of fire hazards It is essential to provide a well ventilated smoking-room, thereby respecting the rights of both smokers and non-smokers.

Ethics, Nursing↗

A molecular perspective of the genetic relationships of G-protein coupled melatonin receptor subtypes.

Successful cloning of melatonin receptors from various target tissues in the past few years has increased our understanding of the molecular signal transduction mechanisms of G-protein coupled melatonin receptors, of which three subtypes (MEL-1A, MEL-1B, and MEL-1C) have been reported in different vertebrates. Based upon melatonin receptor sequences available in the Genbank database, we have performed phylogenetic analyses of the nucleotide and encoded amino acid sequences of G-protein-coupled melatonin receptors, and determined the range of amino acid identities between melatonin receptors of the same and different subtypes. Besides the three well-known subtypes, a potential novel subtype of MEL-1D, as exemplified by unique separation of Xenopus X2.0 sequence (Genbank accession No. U31826) from the others in the protein phylogenetic tree, possibly exists. In addition, one of the chicken brain melatonin receptor sequences has been identified as belonging to the MEL-1B subtype. Our analyses showed that melatonin receptors of the same subtype and different subtypes are likely to share > or = 75% and < 65% amino acid identities, respectively. Phylogenetic analysis based on amino acid comparisons will be needed to determine the subtype status of any pair of melatonin receptor sequences that exhibit > or = 65% to < 75% amino acid identity. Despite the usefulness of genetic relatedness in the subtype classification of G-protein-coupled melatonin receptors, functional correlation of molecular structure may ultimately prove the most comprehensive approach in melatonin receptor classification.

Amino Acid Sequence↗

Vectors for the direct selection of cDNA clones corresponding to mammalian cell mRNA of low abundance.

We have constructed two cDNA cloning vectors which (1) carry the intergenic region of phage f1 and (2) permit efficient cloning (by the Okayama-Berg procedure) of full-length copies of mammalian mRNA in either orientation. Infection of cells harboring these vectors with f1 phage results in the encapsidation of single-stranded (ss) plasmid DNA carrying either the sense or the anti-sense sequence of the cDNA inserts. The complementary nature of the cDNA inserts in two such cDNA libraries facilitates preparative hybridization procedures. These vectors have general applicability to any eukaryotic system where changes in the abundance of mRNA transcripts are to be measured and the corresponding cDNA clones isolated.

Cloning, Molecular↗

Antifreeze protein genes of the winter flounder.

A genomic library of the winter flounder in lambda phage Charon 4 was screened with antifreeze protein cDNA. Nine genomic clones were isolated from three haploid genome equivalents of phage and were grouped into three classes on the basis of restriction mapping and heteroduplex analysis. The three chromosomal regions are non-overlapping and each contain two antifreeze protein genes spaced from 3 to 7 kilobase pairs apart. Genomic Southern blots indicate that these six non-allelic genes represent only 10-20% of the complement of this large multigene family. One gene has been identified by sequencing as a variant of the gene encoding the most abundant antifreeze protein. This gene is 1.0 kilobase pair long and contains an intervening sequence of 0.6 kilobase pairs between the coding region for the bulk of the signal sequence and that coding for the proprotein.

Amino Acid Sequence↗

Glucose and the insulin-releasing drug tolbutamide attenuate the effects of morphine and angiotensin on alcohol consumption.

Animals studies have shown that insulin injections reduce alcohol intake, implicating glucoregulatory processes in alcohol consumption. Angiotensin (ANG) II reduces alcohol intake and promotes glycogen breakdown in the liver but no studies have assessed the role of glucoregulatory processes in ANG II's effect. Similarly, glucose injections attenuate the analgesic and cognitive effects of opiates, yet no studies have assessed the effect of glucose on the well-documented ability of opiates to enhance alcohol consumption. The present experiments further examine the role of glucoregulatory processes in alcohol intake by assessing the effect of glucose injections on morphine-enhanced alcohol consumption and by evaluating the effect of the insulin-releasing drug, tolbutamide, on ANG II-reduced alcohol consumption. Adult male Wistar rats acquired alcohol drinking using the limited access procedure that offers daily 40-min access to both 6% w/v alcohol and water and ensures reliable alcohol drinking in bouts large enough to produce pharmacologically relevant intakes. Experiment 1: after intake stabilized, four groups of rats were first pretreated with vehicle injections and in the next phase, three of the four groups received either 50, 100, or 200 mg/kg glucose intraperitoneally (i.p.) prior to access to alcohol. Neither the vehicle injections nor any of the glucose doses had an effect on alcohol intake. In the final phase all groups continued to receive their respective glucose doses or vehicle but were now also treated with 5 mg/kg morphine sulphate i.p. prior to alcohol access. Morphine stimulated alcohol intake to a similar degree in all groups except the 200 mg/kg group, which showed a significant attenuation in morphine-enhanced alcohol intake. Experiment 2: after intake stabilized, different groups of rats were pretreated with vehicle injections and in the next phase received either 5, 25, 50, or 100 mg/kg tolbutamide or vehicle subcutaneously (s.c.) prior to alcohol access. The vehicle injections did not alter alcohol intake, and only the 100 mg/kg dose of tolbutamide produced a reduction in alcohol intake. In the final phase the groups continued to receive their respective doses of tolbutamide or vehicle but were also treated with 400 micrograms/kg ANG II s.c. immediately prior to alcohol access. ANG II reduced alcohol intake a similar extent in the groups pretreated with 5-50 mg/kg tolbutamide. However, the 100 mg/kg dose of tolbutamide significantly attenuated ANG II's ability to reduce alcohol intake. These results demonstrate that manipulations that engage glucoregulatory processes can influence the mechanism(s) by which morphine and angiotensin respectively increase and decrease alcohol drinking.

Alcohol Drinking↗