Biomedical subjects

Michael Palmer

Publications and source records attributed to Michael Palmer.

At least 19 recordsLinked to original sources

PubMed2007

Efficacy and safety of rosuvastatin 40 mg versus atorvastatin 80 mg in high-risk patients with hypercholesterolemia: results of the POLARIS study.

POLARIS investigated the efficacy and safety of rosuvastatin 40 mg and atorvastatin 80 mg in high-risk patients with hypercholesterolemia. Patients (n=871) were randomized to rosuvastatin 40 mg/day or atorvastatin 80 mg/day for 26 weeks. The primary endpoint was percentage change in LDL-C levels at 8 weeks. Secondary assessments included safety and tolerability, NCEP ATP III LDL-C goal achievement, change in other lipids and lipoproteins at 8 and 26 weeks, and health economics. Mean LDL-C levels were reduced significantly more with rosuvastatin 40 mg than with atorvastatin 80 mg at 8 weeks (-56% versus -52%, p<0.001). The proportion of patients achieving the NCEP ATP III LDL-C goal at 8 weeks was significantly higher in the rosuvastatin 40 mg group (80% versus 72%, p<0.01). Significant differences in the change from baseline in high-density lipoprotein cholesterol (HDL-C) (+9.6% versus +4.4%) and apolipoprotein (Apo)A-I levels (+4.2 versus -0.5) were observed between rosuvastatin and atorvastatin (all p<0.05). Both treatments were well tolerated. Based on a US analysis, rosuvastatin used fewer resources and delivered greater efficacy. Intensive lipid-lowering therapy with rosuvastatin 40 mg/day provided greater LDL-C-lowering efficacy than atorvastatin 80 mg/day, enabling more patients to achieve LDL-C goals. Rosuvastatin may therefore improve LDL-C goal achievement in high-risk patients with hypercholesterolemia.

Aged↗

PubMed2007

Acute, late presentation of colo-continent urinary reservoir fistula.

Complications associated with continent urinary reservoirs are well recognised. Fistulae between the pouch and colon are rare but are documented. This uncommon complication is reported in the early post-operative period in patients who have previously received pelvic radiotherapy. Colonic fistulae are normally secondary to malignancy or diverticular disease. We present the first literature report of a late, acutely presenting colo-pouch fistula secondary to neither malignancy nor diverticular disease. We highlight the need for medical staff to be aware that not all stomas are incontinent and the possible dangers to be aware of when an acutely unwell, debilitated patient is unable to convey this fact.

Aged↗

PubMed2006

Streptococcus agalactiae CAMP factor/protein B does not bind to human IgG.

CAMP factor is an extracellular cytolytic protein produced by Streptococcus agalactiae. CAMP factor has been reported to bind the Fc fragments of immunoglobulin G (IgG) and has therefore also been called protein B, in analogy to protein A of Staphylococcus aureus. We attempted to characterize the interaction of protein B with IgG in more detail. In contrast to protein A, CAMP factor does not inhibit the activation of complement by hemolysin antibodies bound to sheep red cell surfaces. IgG also failed to inhibit the co-hemolytic activity of CAMP factor, which is in disagreement with previous findings. After co-incubation, CAMP factor and IgG were cleanly separated by gel filtration, indicating that no binding had occurred.

Bacterial Proteins↗

PubMed2006

Selective labeling of selenomethionine residues in proteins with a fluorescent derivative of benzyl bromide.

Benzyl bromide is used as a reagent for the selective modification of methionine residues in proteins. We here explored the suitability of the bromobenzyl moiety as a reactive group for the targeted fluorescent labeling of methionine and selenomethionine residues in proteins. A novel labeling reagent (N,N',N'-trimethyl-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)- N'-(p-bromomethylbenzyl)-ethylenediamine, NBD-BBr) was synthesized and tested for reactivity with two model proteins containing single methionine or selenomethionine residues. The amounts of reagent and reactions times required for modification of methionine resulted in side reactions with other amino acid residues, a finding which was also confirmed for benzyl bromide itself. However, with selenomethionine, lower concentrations and shorter reaction times were sufficient for NBD-BBr modification. Under these conditions, labeling was confined to selenomethionine residues with one but not the other model protein. Where applicable, the protein labeling strategy characterized here is rapid and efficient. It should be useful in combination with cysteine-specific labeling if dual site-specific modification is desired.

Amino Acid Sequence↗

PubMed2006

Streptococcus agalactiae CAMP factor binds to GPI-anchored proteins.

CAMP factor (protein B) is a pore-forming protein secreted by Streptococcus agalactiae. It causes lysis of sheep red blood cells when these have been sensitized with staphylococcal sphingomyelinase. We here show that CAMP factor binds to GPI-anchored proteins, and that this interaction involves the carbohydrate core of the GPI-anchor. Enzymatic cleavage of GPI-anchors with phosphatidylinositol-specific phospholipase C strongly reduces the sensitivity of erythrocytes to CAMP factor. Incorporation of alkaline phosphatase, a model GPI-anchored protein, into liposome membranes renders the latter susceptible to permeabilization by CAMP factor. GPI-anchored proteins therefore function as cellular receptors for CAMP factor.

Bacterial Proteins↗

PubMed2006

CMD: a Cotton Microsatellite Database resource for Gossypium genomics.

BACKGROUND: The Cotton Microsatellite Database (CMD) http://www.cottonssr.org is a curated and integrated web-based relational database providing centralized access to publicly available cotton microsatellites, an invaluable resource for basic and applied research in cotton breeding. DESCRIPTION: At present CMD contains publication, sequence, primer, mapping and homology data for nine major cotton microsatellite projects, collectively representing 5,484 microsatellites. In addition, CMD displays data for three of the microsatellite projects that have been screened against a panel of core germplasm. The standardized panel consists of 12 diverse genotypes including genetic standards, mapping parents, BAC donors, subgenome representatives, unique breeding lines, exotic introgression sources, and contemporary Upland cottons with significant acreage. A suite of online microsatellite data mining tools are accessible at CMD. These include an SSR server which identifies microsatellites, primers, open reading frames, and GC-content of uploaded sequences; BLAST and FASTA servers providing sequence similarity searches against the existing cotton SSR sequences and primers, a CAP3 server to assemble EST sequences into longer transcripts prior to mining for SSRs, and CMap, a viewer for comparing cotton SSR maps. CONCLUSION: The collection of publicly available cotton SSR markers in a centralized, readily accessible and curated web-enabled database provides a more efficient utilization of microsatellite resources and will help accelerate basic and applied research in molecular breeding and genetic mapping in Gossypium spp.

Chromosome Mapping↗

PubMed2006

The management of female urinary retention.

Female acute urinary retention (AUR) is relatively uncommon and often poorly managed. There are several common precipitants though much of the literature refers to female AUR as a psychogenic condition. The underlying abnormality is often detrusor failure, not outlet obstruction. Investigations should focus on identifying serious or reversible causes and should include a detailed history and physical examination, urine dipstick, culture and pelvic ultrasound. Patients should be catheterised and reversible causes should be treated. Women who fail to void after catheter removal should be taught ISC. Alpha-blockers are no better than placebo in the treatment of female AUR. There is no role for urethral dilatation. Patients with apparently idiopathic retention should be referred to a urologist with an interest in bladder dysfunction for consideration of urodynamics.

Female↗

PubMed2005

Assessment of quality of life in MA.17: a randomized, placebo-controlled trial of letrozole after 5 years of tamoxifen in postmenopausal women.

PURPOSE: To evaluate the impact of letrozole compared with placebo after adjuvant tamoxifen on quality of life (QOL) in the MA.17 trial. METHODS: Patients completed the Short Form 36-item Health Survey (SF-36) and the Menopause Specific Quality of Life Questionnaire (MENQOL) at baseline, 6 months, and annually. Mean change scores from baseline were compared between groups for summary measures and domains. A response analysis compared the proportion of patients who demonstrated an important change in QOL. RESULTS: Of 5,187 randomly assigned women in the trial, 3,612 (69.9%) participated in the QOL substudy: 1,799 were allocated to placebo and 1,813 were allocated to letrozole. No differences were seen between groups in mean change scores from baseline for the SF-36 physical and mental component summary scores at 6, 12, 24, and 36 months. Small (< 0.2 standard deviations) but statistically significant differences in mean change scores from baseline were seen for the SF-36 domains of physical functioning (12 months), bodily pain (6 months) and vitality (6 and 12 months), and the MENQOL vasomotor (6, 12, and 24 months) and sexual domains (12 and 24 months). On the response analysis, a significant difference was seen between groups for the bodily pain domain (percentage of patients reporting a worsening of QOL, 47% placebo v 51% letrozole; P = .009) and the vasomotor domain (22% placebo v 29% letrozole; P = .001). CONCLUSION: Letrozole did not have an adverse impact on overall QOL. Small effects were seen in some domains consistent with a minority of patients experiencing changes in QOL compatible with a reduction in estrogen synthesis.

Administration, Oral↗

PubMed2005

Sequence, annotation, and analysis of synteny between rice chromosome 3 and diverged grass species.

Rice (Oryza sativa L.) chromosome 3 is evolutionarily conserved across the cultivated cereals and shares large blocks of synteny with maize and sorghum, which diverged from rice more than 50 million years ago. To begin to completely understand this chromosome, we sequenced, finished, and annotated 36.1 Mb ( approximately 97%) from O. sativa subsp. japonica cv Nipponbare. Annotation features of the chromosome include 5915 genes, of which 913 are related to transposable elements. A putative function could be assigned to 3064 genes, with another 757 genes annotated as expressed, leaving 2094 that encode hypothetical proteins. Similarity searches against the proteome of Arabidopsis thaliana revealed putative homologs for 67% of the chromosome 3 proteins. Further searches of a nonredundant amino acid database, the Pfam domain database, plant Expressed Sequence Tags, and genomic assemblies from sorghum and maize revealed only 853 nontransposable element related proteins from chromosome 3 that lacked similarity to other known sequences. Interestingly, 426 of these have a paralog within the rice genome. A comparative physical map of the wild progenitor species, Oryza nivara, with japonica chromosome 3 revealed a high degree of sequence identity and synteny between these two species, which diverged approximately 10,000 years ago. Although no major rearrangements were detected, the deduced size of the O. nivara chromosome 3 was 21% smaller than that of japonica. Synteny between rice and other cereals using an integrated maize physical map and wheat genetic map was strikingly high, further supporting the use of rice and, in particular, chromosome 3, as a model for comparative studies among the cereals.

Arabidopsis↗

PubMed2005

Dual-targeted labeling of proteins using cysteine and selenomethionine residues.

A new strategy for dual site-selective labeling of proteins that uses metabolically incorporated selenomethionine as a target for covalent modification by iodoacetamide derivatives, forming selenonium salts, is described. In the absence of free cysteine, labeling is specific and efficient. Dual-targeted labeling of a protein can be achieved with combinations of unique cysteine and methionine residues, if the cysteine is labeled first with a maleimide or another reagent that does not react with the selenomethionine. The method should be useful in biophysical applications such as fluorescence energy transfer.

Bacterial Proteins↗

PubMed2005

L-lactate measures in brain tissue with ceramic-based multisite microelectrodes.

A newly developed multisite array microelectrode for in vivo measurements of L-lactate is presented. The resulting microelectrode is composed of three functional layers. First, Nafion is used to repel interfering electroactive anions, such as ascorbate. Second, L-lactate oxidase immobilized onto the recording sites is used to convert L-lactate to hydrogen peroxide. The H2O2 produced is proportional to L-lactate concentrations and is quantified at the platinum recording sites. Third, a layer of polyurethane is coated over the L-lactate oxidase to adjust the linear range of the microelectrode to one that is compatible with in vivo measurements. This layer reduces the amount of L-lactate that diffuses to the enzyme while not significantly limiting oxygen diffusion. The resulting L-lactate microelectrodes were linear to 20 mM (R2 = 0.997 +/- 0.001) and beyond in some cases with detection limits of 0.078 +/- 0.013 mM (n = 12). The selectivity and response time of these electrodes make them suitable for in vivo measurements in brain tissue. Self-referencing recordings may be utilized to further improve the selectivity of the recordings. However this is not necessary for most applications in the brain, because the resting and stimulated levels of dopamine (DA), norepinephrine (NE), and other potentially interfering cations are two to three orders of magnitude lower than that of in vivo L-lactate, which is in the millimolar range. Preliminary in vivo measures of L-lactate in the brain of anesthetized rats support that the microelectrodes are capable of measuring rapid endogenous changes in vivo.

Animals↗

PubMed2004

Cholesterol and the activity of bacterial toxins.

Cholesterol may affect the activity of microbial toxins in a direct, specific way, or it may exert indirect effects because of its role in membrane fluidity, membrane line tension, and in the stabilization of rafts in the cytoplasmic membrane. The thiol-activated toxins of gram-positive bacteria, and the cytolysin of Vibrio cholerae are presented as examples of specific toxin-cholesterol interaction. Several mechanisms of indirect effects of cholesterol are discussed using examples such as Staphylococcus aureus alpha-hemolysin, aerolysin, and diphtheria toxin.

Animals↗

PubMed2004

Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body.

In Drosophila melanogaster, ageing is slowed when insulin-like signalling is reduced: life expectancy is extended by more than 50% when the insulin-like receptor (InR) or its receptor substrate (chico) are mutated, or when insulin-producing cells are ablated. But we have yet to resolve when insulin affects ageing, or whether insulin signals regulate ageing directly or indirectly through secondary hormones. Caenorhabditis elegans lifespan is also extended when insulin signalling is inhibited in certain tissues, or when repressed in adult worms, and this requires the forkhead transcription factor (FOXO) encoded by daf-16 (ref. 6). The D. melanogaster insulin-like receptor mediates phosphorylation of dFOXO, the equivalent of nematode daf-16 and mammalian FOXO3a. We demonstrate here that dFOXO regulates D. melanogaster ageing when activated in the adult pericerebral fat body. We further show that this limited activation of dFOXO reduces expression of the Drosophila insulin-like peptide dilp-2 synthesized in neurons, and represses endogenous insulin-dependent signalling in peripheral fat body. These findings suggest that autonomous and non-autonomous roles of insulin signalling combine to control ageing.

Aging↗

PubMed2004

Arthrobacter aurescens TC1 atrazine catabolism genes trzN, atzB, and atzC are linked on a 160-kilobase region and are functional in Escherichia coli.

Arthrobacter aurescens strain TC1 metabolizes atrazine to cyanuric acid via TrzN, AtzB, and AtzC. The complete sequence of a 160-kb bacterial artificial chromosome clone indicated that trzN, atzB, and atzC are linked on the A. aurescens genome. TrzN, AtzB, and AtzC were shown to be functional in Escherichia coli. Hybridization studies localized trzN, atzB, and atzC to a 380-kb plasmid in A. aurescens strain TC1.

Arthrobacter↗

PubMed2003

Differential interaction of the two cholesterol-dependent, membrane-damaging toxins, streptolysin O and Vibrio cholerae cytolysin, with enantiomeric cholesterol.

Membrane cholesterol is essential to the activity of at least two structurally unrelated families of bacterial pore-forming toxins, represented by streptolysin O (SLO) and Vibrio cholerae cytolysin (VCC), respectively. Here, we report that SLO and VCC differ sharply in their interaction with liposome membranes containing enantiomeric cholesterol (ent-cholesterol). VCC had very low activity with ent-cholesterol, which is in line with a stereospecific mode of interaction of this toxin with cholesterol. In contrast, SLO was only slightly less active with ent-cholesterol than with cholesterol, suggesting a rather limited degree of structural specificity in the toxin-cholesterol interaction.

Bacterial Proteins↗

PubMed2003

Characterization of Streptococcus agalactiae CAMP factor as a pore-forming toxin.

A recombinant form of CAMP factor of Streptococcus agalactiae has been expressed as glutathione S-transferase-CAMP fusion protein in Escherichia coli. After thrombin cleavage of the fusion protein, the recombinant CAMP factor exhibited hemolytic activity comparable with that of the native form. Osmotic protection experiments with polyethylene glycols show that CAMP factor forms discrete transmembrane pores with a diameter upward of 1.6 nm on susceptible membranes; electron microscopy reveals circular membrane lesions of heterogeneous size, up to 12-15 nm in diameter. Liposome permeabilization studies show that pore formation is a highly cooperative process, which suggests that it involves the oligomerization of CAMP factor. Chemical cross-linking experiments also support an oligomeric mode of action.

Animals↗

PubMed2003

Client commitment language during motivational interviewing predicts drug use outcomes.

Client language from a motivational interview (MI) and drug use outcome were investigated. Interview videotapes of 84 drug abusers were coded for frequency and strength of utterances expressing commitment, desire, ability, need, readiness, and reasons to change or maintain their habit. Cluster analysis of proportion days abstinent (PDA) revealed 3 groups: high PDA at intake and follow-up (3, 6, 9, 12 months; maintainers); low intake PDA/high follow-up PDA (changers); and low intake PDA/low to moderate follow-up PDA (stragglers). Distinct group patterns emerged for commitment strength (CS) during MI. Clients dishonest in checklist self-report exhibited CS similar to stragglers. CS for client evaluation of a change plan predicted outcome PDA. CS was predicted by strength of desire, ability, need, and reasons, but more strongly predicted outcome PDA, suggesting CS is a pathway for their influence on behavior.

Adult↗

PubMed2003

Efflux of cytoplasmically acting antibiotics from gram-negative bacteria: periplasmic substrate capture by multicomponent efflux pumps inferred from their cooperative action with single-component transporters.

In gram-negative bacteria, coexpression of single- and multicomponent efflux pumps may result in multiplicative enhancement of the level of resistance against cytoplasmically acting antibiotics. Here, a simple model is presented to show that this cooperative effect can be accounted for only if substrate capture by the multicomponent efflux transporter occurs in the periplasm but not the cytosol.

Anti-Bacterial Agents↗