Ventricular arrhythmias during ergonovine-induced episodes of variant angina

Of 95 consecutive patients with active variant angina who underwent ergonovine testing in the coronary care unit while off treatment, 24 (25%) developed serious ventricular arrhythmias: ventricular tachycardia in eight, bigeminy in seven, pairs in five, and frequent ventricular extrasystoles in four. Ergonovine-induced arrhythmias were observed more often in patients with anterior than inferior ST segment elevation (p less than 0.05). ST segment elevation was significantly higher (10.3 +/- 8.1 vs 3.1 +/- 2.1 mm) in patients who developed arrhythmias. All ventricular arrhythmias began within 3 minutes after the onset of ST segment elevation. The intravenous administration of nitroglycerin eliminated arrhythmias in 22 of 24 cases; in only two patients did ventricular arrhythmias develop after the administration of nitroglycerin. Serious ventricular arrhythmias were found during spontaneous variant angina attacks in 14 of 24 patients with ergonovine-induced arrhythmias compared to 16 of 71 patients without ergonovine-induced arrhythmias (p less than 0.001). We conclude that arrhythmias during ergonovine testing are most often caused by ischemia and not reperfusion. Patients with arrhythmias during ergonovine-induced attacks are more likely to have arrhythmias during spontaneous attacks.     

A Random Sample from Wales

S ummary . The serum iron, iron binding capacity and transferrin saturation has been estimated in a random sample of the Welsh population. The results indicate that iron deficient erythropoiesis is not uncommon, being present in 22 per cent of women and 6 per cent of men. Iron deficiency has only a low correlation with haemoglobin concentration and it is commonly found in subjects with a normal haemoglobin concentration by conventional standards.     

HPA-1 typing by PCR amplification with sequence-specific primers (PCR-SSP): a rapid and simple technique

Summary. A DNA-based method was developed to genotype donors for the human platelet antigens HPA-la and -1b. Sequence-specific primers (SSP) were used in the polymerase chain reaction (PCR) which allowed the HPA-la/la. -lb/lb and -la/lb genotypes to be determined by PCR alone, no second analytical stage was required. 10 donors were tested by PCR-SSP and the results were concordant with serological phenotyping and independent DNA analysis.     

Comparative analysis of mammalian Y chromosomes illuminates ancestral structure and lineage-specific evolution

Although more than thirty mammalian genomes have been sequenced to draft quality, very few of these include the Y chromosome. This has limited our understanding of the evolutionary dynamics of gene persistence and loss, our ability to identify conserved regulatory elements, as well our knowledge of the extent to which different types of selection act to maintain genes within this unique genomic environment. Here, we present the first MSY (male-specific region of the Y chromosome) sequences from two carnivores, the domestic dog and cat. By combining these with other available MSY data, our multiordinal comparison allows for the first accounting of levels of selection constraining the evolution of eutherian Y chromosomes. Despite gene gain and loss across the phylogeny, we show the eutherian ancestor retained a core set of 17 MSY genes, most being constrained by negative selection for nearly 100 million years. The X-degenerate and ampliconic gene classes are partitioned into distinct chromosomal domains in most mammals, but were radically restructured on the human lineage. We identified multiple conserved noncoding elements that potentially regulate eutherian MSY genes. The acquisition of novel ampliconic gene families was accompanied by signatures of positive selection and has differentially impacted the degeneration and expansion of MSY gene repertoires in different species.Y chromosomes have arisen independently in divergent evolutionary lineages across the eukaryotic tree of life (Rice 1996; Marin and Baker 1998; Liu et al. 2004; Graves 2006; Koerich et al. 2008; Carvalho et al. 2009; Kaiser and Bachtrog 2010). While many genes are known to be Y-linked, the actual number of Y chromosomes that have been sequenced is extremely small (Skaletsky et al. 2003; Hughes et al. 2005; Kuroki et al. 2006; Clark et al. 2007; Koerich et al. 2008; Carvalho et al. 2009; Hughes et al. 2010, 2012) in relation to the rapid rate at which whole genomes are presently being sequenced. This reduced emphasis on sequencing Y chromosomes can be primarily attributed to their presumed low gene content and large amounts of repetitive DNA, that is often arrayed into long stretches of nearly identical sequence which precludes the use of shotgun sequencing approaches to assemble Y chromosome sequence into large, contiguous scaffolds. These assembly problems are further exacerbated when applying short-read next-generation sequence methods (Alkan et al. 2011).The most completely sequenced and annotated Y chromosomes are from three recently diverged catarrhine primates: human, chimpanzee, and rhesus macaque (Skaletsky et al. 2003; Hughes et al. 2005, 2010, 2012; Kuroki et al. 2006 ). Comparisons between these species offer an important glimpse into the immense structural variation and complexity that can emerge on the Y within a very short period of evolutionary time. However, these three primate species last shared a common ancestor ∼21 million years ago (Mya) (Meredith et al. 2011) and thus offer limited comparative breadth to discriminate characteristics present across most mammalian Y chromosomes from idiosyncratic features reflective of a small evolutionary sample. This lack of phylogenetic scope has (1) hampered identification of the ancestral properties of eutherian Y chromosomes, (2) obscured broader patterns of evolutionary constraint and selection in a nonrecombining environment, and (3) hidden the frequency with which novel genes arise and/or acquire new functions in species with diverse phenotypes and reproductive strategies.To expand our knowledge of eutherian Y chromosome structure and gene function, we generated the first extensive MSY (male-specific Y chromosome) sequence from two members of the Carnivora: the domestic cat, Felis silvestris catus, and domestic dog, Canis lupus familiaris. These two carnivore genomes provide a phylogenetically distinct vantage point with which to interpret the evolutionary patterns observed in the primate MSY comparisons, diverging from each other ∼55 Mya, and from primates ∼92 Mya (Meredith et al. 2011). Our combined analysis of two carnivore and three primate MSY sequences, together with physical mapping and functional sequence data from the mouse MSY, represent the first multiordinal comparison assessing deeper levels of evolutionary constraint. We also present a complete analysis of patterns of negative and positive selection to assess their effects on MSY degeneration and expansion.     

Development and characterisation of 20 novel microsatellite markers for the little blue penguin (Eudyptula minor) using next-generation sequencing

Conservation Genetics Resources - The world’s smallest penguin, Eudyptula minor, exhibits substantial mtDNA differentiation among populations, suggesting the possibility of multiple taxa. We...     

Contrast agents for MRI

Molecular imaging is a rapidly growing field with the potential to revolutionize cardiovascular medicine by shifting diagnostic focus from functional abnormalities which occur late in a disease process to the biochemical events which precipitate the earliest stages of disease. MRI is a modality well suited to this task as it allows a variety of contrast mechanisms for detection of epitopes of interest, as well as high-resolution anatomical localization and functional information. In this review, we discuss the widerange of available molecular MRI contrast agents and their application to diseases such as atherosclerosis, thrombus imaging, and stem cell tracking, along with opportunities for molecularly targeted drug delivery.     

Comparison of effectiveness of atorvastatin 10 mg versus 80 mg in reducing major cardiovascular events and repeat revascularization in patients with previous percutaneous coronary intervention (post hoc analysis of the Treating to New Targets [TNT] Study)

The Treating to New Targets (TNT) study demonstrated that intensive atorvastatin therapy to achieve low-density lipoprotein cholesterol concentrations well below recommended target levels provides an incremental clinical benefit in patients with stable coronary artery disease. This post hoc analysis of the TNT study was conducted to investigate whether this benefit extends to patients with previous percutaneous coronary intervention (PCI). A total of 10,001 patients with clinically evident coronary artery disease, including 5,407 patients with previous PCI, were randomized to atorvastatin 10 or 80 mg/day and followed for a median of 4.9 years. The primary end point was the occurrence of a first major cardiovascular event. Revascularization, a component of a secondary end point, was also examined. In patients with previous PCI, mean low-density lipoprotein cholesterol levels at study end were 79.5 mg/dl in the 80-mg arm and 100.8 mg/dl in the 10-mg arm. First major cardiovascular events occurred in 230 patients (8.6%) receiving high-dose atorvastatin and 289 patients (10.6%) receiving low-dose atorvastatin (hazard ratio 0.79, 95% confidence interval 0.67 to 0.94, p = 0.008). Repeat revascularization during follow-up (PCI or coronary artery bypass grafting) was performed in 466 patients (17.3%) in the 80-mg arm and 624 patients (22.9%) in the 10-mg arm (hazard ratio 0.73, 95% confidence interval 0.65 to 0.82, p <0.0001). In conclusion, intensive lipid lowering to a mean low-density lipoprotein cholesterol level of 79.5 mg/dl (2.1 mmol/L) with atorvastatin 80 mg/day in patients with previous PCI reduces major cardiovascular events by 21% and repeat revascularizations by 27% compared with a less intensive lipid-lowering regimen.     

Stimulation of luteinizing hormone release by sodium fluoride is independent of protein kinase-C activity and unaffected by desensitization to gonadotropin-releasing hormone

GnRH stimulates secretion of pituitary LH by increasing intracellular calcium. Increased calcium may result from activation of phospholipase-C, since there is an increase in inositol phosphates and diacylglycerol, and a redistribution of protein kinase-C (PKC) from cytosolic to a particulate cell fraction in GnRH-stimulated pituitary cultures. A GTP-binding protein (G-protein) may mediate GnRH actions, since GTP stimulates LH release in permeabilized gonadotropes and decreases receptor affinity for a GnRH analog. In the present study we have used sodium fluoride, an exogenous activator of G-proteins, to investigate the possibility of a G-protein link between GnRH receptor activation, phospholipase-C activity, and LH release. Treatment of primary pituitary cell cultures from immature female rats with sodium fluoride stimulated the release of 20% total cellular LH and increased inositol phosphate accumulation. Sodium fluoride-stimulated LH release was insensitive to cholera toxin and pertussis toxin. Sodium fluoride-stimulated LH release was additive with a maximally effective concentration of phorbol 12-myristate 13-acetate and was not inhibited by depletion of cellular PKC, suggesting that PKC does not mediate sodium fluoride effects. Treatment of cultures with 3 mM EGTA and 10 nM GnRH for 5 and 16 h reduced pituitary responsiveness to subsequent treatment with GnRH, but had no effect on sodium fluoride-stimulated LH release. Although the precise mechanism of sodium fluoride-stimulated LH release remains to be described, our results support a role for a G-protein in regulation of LH release by the releasing hormone.     

Sequence identity in the nick regions of IncP plasmid transfer origins and T-DNA borders of Agrobacterium Ti plasmids.

The IncP antibiotic-resistance plasmids transfer to a broad range of bacterial species. The RK2 origin of DNA transfer (oriT) consists of a 250-base-pair segment including the single-stranded cleavage site (nic) needed to generate the DNA strand believed to be transferred. Deletion derivatives and a bank of hydroxylamine-generated oriT mutants were screened for loss of transferability. DNA regions flanking both sides of nic are required for optimal transfer of the oriT clone. Of the chemically induced mutants, critical base-pair changes that dramatically reduced transfer frequency were found in a 10-base-pair region adjacent to nic. Relaxation (nicking) assays performed with these point mutants using protein-DNA complexes reconstituted in vitro revealed a correlation between DNA nicking and transfer frequency. Base-pair changes within the proximal arm of an inverted repeat upstream from the nick site resulted in reduced binding of the essential transfer protein TraJ and correspondingly reduced transfer frequencies. The results support a model of relaxosome formation involving at least two essential proteins: TraI and TraJ. The nick region defined by the point mutants was located in a segment known to be nearly identical in the related plasmid R751. This sequence was also found to be highly conserved in both border junctions of the transfer DNA (T-DNA) of plant tumor-inducing plasmids of Agrobacterium tumefaciens, indicating a relationship between IncP-mediated broad-host-range bacterial conjugation and T-DNA transfer to plants.     

Successful closure of coronary artery perforation using makeshift stent sandwich.

An elderly woman underwent stenting of mid left anterior descending coronary artery (LAD) 2 days after myocardial infarction. During high-pressure stent dilatation, vessel perforation was noted. We assembled a "stent sandwich" in the cardiac catheterization laboratory and used it successfully to seal the perforation with good angiographic result. Although the long-term patency remains an issue, this case demonstrates the feasibility of using makeshift covered-stent as a bailout for arterial perforation in selected cases where emergency thoracotomy is undesirable.