Acute management of atrial fibrillation with acute haemodynamic instability and in the postoperative setting.
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Acute Disease↗
Biomedical subjects
C J Mann
Publications and source records attributed to C J Mann.
Simplifying thrombolysis decisions in patients with left bundle branch block.
OBJECTIVES: To redesign and simplify an existing decision algorithm for the management of patients who present to the emergency department with chest pain and left bundle branch block (LBBB) based on the Sgarbossa criteria. To compare its reliability with the current algorithm. METHODS: A simplified algorithm was created and tested against the existing algorithm. Electrocardiograms (ECGs) of patients with LBBB were presented to 10 emergency department doctors with both old and new algorithms a week apart. Six ECGs displayed the relevant criteria for thrombolysis and had proven acute myocardial infarction (AMI) based on a gold standard of enzyme measurements. Subjects were asked whether or not they would thrombolyse a patient presenting with the given ECG using each of the algorithms as a guide. RESULTS: The new algorithm has demonstrated improvements in terms of an increase in appropriate thrombolysis and a reduction in inappropriate thrombolysis. Specificity for AMI rose from 0.85 to 0.99 and sensitivity from 0.38 to 0.6. kappa score showed greater agreement with the gold standard. CONCLUSION: Patients with AMI and LBBB have a significantly poorer outcome than those without LBBB. Despite this, thrombolysis is less likely to be given to patients with AMI and LBBB. This study demonstrates that in part this is because of cognitive difficulties using the current algorithm. The proposed proforma addresses these issues and provides a simple tool to aid appropriate treatment in this group of patients.
Algorithms↗
Enhanced in vivo delivery of antisense oligonucleotides to restore dystrophin expression in adult mdx mouse muscle.
The use of antisense oligonucleotides (AOs) to induce exon skipping leading to generation of an in-frame dystrophin protein product could be of benefit in around 70% of Duchenne muscular dystrophy patients. We describe the use of hyaluronidase enhanced electrotransfer to deliver uncomplexed 2'-O-methyl modified phosphorothioate AO to adult dystrophic mouse muscle, resulting in dystrophin expression in 20-30% of fibres in tibialis anterior muscle after a single injection. Although expression was transient, many of the corrected fibres initially showed levels of dystrophin expression well above the 20% of endogenous previously shown to be necessary for phenotypic correction of the dystrophic phenotype.
Animals↗
Observational research methods. Research design II: cohort, cross sectional, and case-control studies.
Cohort, cross sectional, and case-control studies are collectively referred to as observational studies. Often these studies are the only practicable method of studying various problems, for example, studies of aetiology, instances where a randomised controlled trial might be unethical, or if the condition to be studied is rare. Cohort studies are used to study incidence, causes, and prognosis. Because they measure events in chronological order they can be used to distinguish between cause and effect. Cross sectional studies are used to determine prevalence. They are relatively quick and easy but do not permit distinction between cause and effect. Case controlled studies compare groups retrospectively. They seek to identify possible predictors of outcome and are useful for studying rare diseases or outcomes. They are often used to generate hypotheses that can then be studied via prospective cohort or other studies.
Case-Control Studies↗
A retrospective clinical and radiographic review of 173 hydroxyapatite-coated screw cups with 5- to 10-year follow-up, showing low revision rates for fixation failure.
We reviewed the midterm results of 173 hydroxyapatite-coated screw cups. The average follow-up was 6.5 years (range, 5-9 years). The follow-up rate was 93%. Patients were assessed using the Merle D'Aubigne-Postel clinical scoring scale and by radiographic review. Two patients had revision surgery for recurrent dislocation (1.2%), 3 patients were revised for aseptic loosening (1.7%), 1 patient underwent revision surgery because of deep prosthetic infection (0.6%), and 2 patients were revised for polyethylene wear without loosening (1.2%), which gave a total revision rate of 4.7%. The average postoperative Merle D'Aubigne-Postel scores were 5.7 for pain, 5.5 for range of motion, and 5.4 for function.
Aged↗
Choline containing metabolites during cell transfection: an insight into magnetic resonance spectroscopy detectable changes.
Increases in choline containing metabolites have been associated with a number of disorders, including malignant cell growth. In this study, high resolution magic angle spinning (1)H nuclear magnetic resonance spectroscopy was employed to monitor metabolite changes during cell transfection, and an increase in phosphocholine was detected. This increase appears to be correlated with cell membrane disruption associated with the insertion of plasmid DNA into cells, since the level of phosphocholine in mock transfected cells was comparable to that of control cells. These data suggest choline containing metabolite changes detected in vivo using magnetic resonance spectroscopy relate to cell membrane disruption.
Choline↗
Antisense-induced exon skipping and synthesis of dystrophin in the mdx mouse.
Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease arising from defects in the dystrophin gene, typically nonsense or frameshift mutations, that preclude the synthesis of a functional protein. A milder, allelic version of the disease, Becker muscular dystrophy, generally arises from in-frame deletions that allow synthesis of a shorter but still semifunctional protein. Therapies to introduce functional dystrophin into dystrophic tissue through either cell or gene replacement have not been successful to date. We report an alternative approach where 2'-O-methyl antisense oligoribonucleotides have been used to modify processing of the dystrophin pre-mRNA in the mdx mouse model of DMD. By targeting 2'-O-methyl antisense oligoribonucleotides to block motifs involved in normal dystrophin pre-mRNA splicing, we induced excision of exon 23, and the mdx nonsense mutation, without disrupting the reading frame. Exon 23 skipping was first optimized in vitro in transfected H-2K(b)-tsA58 mdx myoblasts and then induced in vivo. Immunohistochemical staining demonstrated the synthesis and correct subsarcolemmal localization of dystrophin and gamma-sarcoglycan in the mdx mouse after intramuscular delivery of antisense oligoribonucleotide:liposome complexes. This approach should reduce the severity of DMD by allowing a dystrophic gene transcript to be modified, such that it can be translated into a Becker-dystrophin-like protein.
Animals↗
Evaluation of a short interspersed nucleotide element in the 3' untranslated region of the defective dystrophin gene of dogs with muscular dystrophy.
OBJECTIVES: To determine the distribution of a 231-base pair (bp) element in the dystrophin gene 3' untranslated region (UTR) in a colony of Golden Retrievers with muscular dystrophy and other unrelated dogs and to estimate the frequency of recombination for the canine dystrophin gene. ANIMALS: 77 dogs from the Golden Retriever Muscular Dystrophy (GRMD) colony at the Murdoch Veterinary School and 30 unrelated dogs from the Murdoch University Veterinary Clinic. PROCEDURE: Samples of blood or hair from dogs were used for amplification of DNA, using primers to the canine dystrophin 3' UTR. RESULTS: The DNA from affected dogs generated a larger PCR product than that obtained from clinically normal dogs. Products were cloned and sequenced, and the difference in size was found to be attributable to a 231-bp short interspersed nucleotide element (SINE). The SINE was found in all affected dogs in the colony but not in most unaffected puppies in the colony. Eighteen of 19 dogs in the colony were heterozygous for the GRMD mutation, and 7 of 30 unrelated dogs also were heterozygous for the SINE. CONCLUSION AND CLINICAL RELEVANCE: Evidence of recombination between the GRMD mutation and the SINE was observed in only 4 dogs (2 sets of littermates) in the GRMD colony. Incidence of this SINE in a few unrelated dogs suggests that this particular insertion into the dystrophin gene may have been a recent event. The SINE in the dystrophin 3' UTR did not have an apparent influence on dystrophin mRNA concentrations.
3' Untranslated Regions↗
A survey of reading, writing, and oral communication skills in North American veterinary medical colleges.
In the 1989 report by the Pew National Veterinary Education Program (PNVEP), communication skills topped the list of characteristics the veterinary graduate should possess in order to function effectively in the twenty-first century. To determine the reading, writing, and oral communication requirements and opportunities in veterinary curricula in the US and Canada, and to determine the perceived communication tasks that might be commonly required of practicing veterinarians in the next century, we sent a 15-item communications skills questionnaire to the academic deans of the 31 veterinary curricula in the US and Canada. The results reinforce the importance of communication skills in veterinary medicine, as detailed by the PNVEP over 10 years ago. Based on the responses to our questionnaire and on our own experiences with veterinary medical students, we make several recommendations to enhance communication instruction in veterinary medical curricula.
Canada↗
Proposal writing for Healthy People 2010: veterinary student authors win Hill's Public Health Awards and DHHS secretary's Awards for Innovations in Health Promotion and Disease Prevention.
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Awards and Prizes↗
Purification and characterization of S-adenosyl-L-methionine:benzoic acid carboxyl methyltransferase, the enzyme responsible for biosynthesis of the volatile ester methyl benzoate in flowers of Antirrhinum majus.
S-Adenosyl-L-methionine:benzoic acid carboxyl methyltransferase (BAMT) catalyzes the transfer of the methyl group of S-adenosyl-L-methionine (SAM) to the carboxyl group of benzoic acid to make the volatile ester methyl benzoate, one of the most abundant scent compounds of snapdragon, Antirrhinum majus. The enzyme was purified from upper and lower petal lobes of 5- to 10-day-old snapdragon flowers using DE53 anion exchange, Phenyl-Sepharose 6FF, and Mono-Q chromatography. The purified protein has a pH optimum of 7.5 and is highly specific for benzoic acid, with no activity toward several other naturally occurring substrates such as salicylic acid, cinnamic acid, and their derivatives. The molecular mass values for native and denatured protein were 100 and 49 kDa, respectively, suggesting that the active enzyme is a homodimer. The addition of monovalent cations K+ and NH4+ stimulates BAMT activity by a factor of 2, whereas the addition of Fe2+ and Cu2+ has a strong inhibitory effect. Plant-purified BAMT has Km values of 28 microM and 1.1 mM for SAM and benzoic acid, respectively (87 microM and 1.6 mM, respectively, for plant BAMT expressed in Escherichia coli). Product inhibition studies showed competitive inhibition between SAM and S-adenosyl-L-homocysteine (SAH), with a Ki of 7 microM, and noncompetitive inhibition between benzoic acid and SAH, with a Ki of 14 microM.
Benzoates↗
Developmental regulation of methyl benzoate biosynthesis and emission in snapdragon flowers.
In snapdragon flowers, the volatile ester methyl benzoate is the most abundant scent compound. It is synthesized by and emitted from only the upper and lower lobes of petals, where pollinators (bumblebees) come in contact with the flower. Emission of methyl benzoate occurs in a rhythmic manner, with maximum emission during the day, which correlates with pollinator activity. A novel S-adenosyl-l-methionine:benzoic acid carboxyl methyl transferase (BAMT), the final enzyme in the biosynthesis of methyl benzoate, and its corresponding cDNA have been isolated and characterized. The complete amino acid sequence of the BAMT protein has only low levels of sequence similarity to other previously characterized proteins, including plant O-methyl transferases. During the life span of the flower, the levels of methyl benzoate emission, BAMT activity, BAMT gene expression, and the amounts of BAMT protein and benzoic acid are developmentally and differentially regulated. Linear regression analysis revealed that production of methyl benzoate is regulated by the amount of benzoic acid and the amount of BAMT protein, which in turn is regulated at the transcriptional level.
Amino Acid Sequence↗
Bacterial reductive dissolution of crystalline Fe(III) oxide in continuous-flow column reactors.
Bacterial reductive dissolution of synthetic crystalline Fe(III) oxide-coated sand was studied in continuous-flow column reactors in comparison with parallel batch cultures. The cumulative amount of aqueous Fe(II) exported from the columns over a 6-month incubation period corresponded to (95.0 +/- 3.7)% (n = 3) of their original Fe(III) content. Wet-chemical analysis revealed that only (6.5 +/- 3.2)% of the initial Fe(III) content remained in the columns at the end of the experiment. The near-quantitative removal of Fe was visibly evidenced by extensive bleaching of color from the sand in the columns. In contrast to the column reactors, Fe(II) production quickly reached an asymptote in batch cultures, and only (13.0 +/- 2.2)% (n = 3) of the Fe(III) oxide content was reduced. Sustained bacterial-cell growth occurred in the column reactors, leading to the production and export of a quantity of cells 100-fold greater than that added during inoculation. Indirect estimates of cell growth, based on the quantity of Fe(III) reduced, suggest that only an approximate doubling of initial cell abundance was likely to have occurred in the batch cultures. Our results indicate that removal of biogenic Fe(II) via aqueous-phase transport in the column reactors decreased the passivating influence of surface-bound Fe(II) on oxide reduction activity, thereby allowing a dramatic increase in the extent of Fe(III) oxide reduction and associated bacterial growth. These findings have important implications for understanding the fate of organic and inorganic contaminants whose geochemical behavior is linked to Fe(III) oxide reduction.
Bacteria↗
Combined Galeazzi and Monteggia forearm fracture.
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Adult↗
Veterinary students lead the way to a healthier nation in 2010.
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Animals↗
Baculovirus expression and biochemical characterization of the human microsomal triglyceride transfer protein.
The microsomal triglyceride transfer protein (MTP) complexed to protein disulphide isomerase (PDI) is obligatory for the assembly of chylomicrons and very-low-density lipoproteins. The determination of the atomic structure of the MTP-PDI heterodimer has important implications for the treatment of those forms of hyperlipidaemia associated with the overproduction of very-low-density lipoproteins, which predispose to premature coronary heart disease. To perform structural studies of the human MTP-PDI complex it was necessary to produce milligram quantities of pure protein. We chose the baculovirus expression system for this purpose. Insects cells were co-infected with recombinant viruses encoding FLAG-tagged MTP and His-tagged PDI; the resulting heterodimer was purified by affinity chromatography. From 5 litres of insect cells, 4-6 mg of more than 95% pure recombinant protein was obtained. CD and attenuated total reflection Fourier-transform infrared spectroscopy indicate that the purified protein has around 34% alpha-helical and 33% beta-structure content. The recombinant protein had a comparable triglyceride transfer activity to that of bovine MTP-PDI. The production of polyclonal antibodies raised against the MTP and PDI subunits of the purified protein is described. The present study demonstrates the feasibility of expressing two proteins at high levels in insect cells and describes a transferable methodology for the purification of the resulting protein complex.
Amino Acid Sequence↗
A common binding site on the microsomal triglyceride transfer protein for apolipoprotein B and protein disulfide isomerase.
The assembly of triglyceride-rich lipoproteins requires the formation in the endoplasmic reticulum of a complex between apolipoprotein B (apoB), a microsomal triglyceride transfer protein (MTP), and protein disulfide isomerase (PDI). In the MTP complex, the amino-terminal region of MTP (residues 22-303) interacts with the amino-terminal region of apoB (residues 1-264). Here, we report the identification and characterization of a site on apoB between residues 512 and 721, which interacts with residues 517-603 of MTP. PDI binds in close proximity to this apoB binding site on MTP. The proximity of these binding sites on MTP for PDI and amino acids 512-721 of apoB was evident from studies carried out in a yeast two-hybrid system and by co-immunoprecipitation. The expression of PDI with MTP and apoB16 (residues 1-721) in the baculovirus expression system reduced the amount of MTP co-immunoprecipitated with apoB by 73%. The interaction of residues 512-721 of apoB with MTP facilitates lipoprotein production. Mutations of apoB that markedly reduced this interaction also reduced the level of apoB-containing lipoprotein secretion.
Amino Acid Sequence↗
The structure of vitellogenin provides a molecular model for the assembly and secretion of atherogenic lipoproteins.
The assembly of atherogenic lipoproteins requires the formation in the endoplasmic reticulum of a complex between apolipoprotein (apo)B, a microsomal triglyceride transfer protein (MTP) and protein disulphide isomerase (PDI). Here we show by molecular modelling and mutagenesis that the globular amino-terminal regions of apoB and MTP are closely related in structure to the ancient egg yolk storage protein, vitellogenin (VTG). In the MTP complex, conserved structural motifs that form the reciprocal homodimerization interfaces in VTG are re-utilized by MTP to form a stable heterodimer with PDI, which anchors MTP at the site of apoB translocation, and to associate with apoB and initiate lipid transfer. The structural and functional evolution of the VTGs provides a unifying scheme for the invertebrate origins of the major vertebrate lipid transport system.
Amino Acid Sequence↗