Molecular genecology of temperature response in Lolium perenne: 1. preliminary analysis to reduce false positives.

Molecular genecology is the study of geographical clines in frequencies of molecular markers and their relationship to ecological clines in environmental conditions. This study outlines the principles underlying the selection of populations, focusing on avoiding 'false positives'- noncausal correlations between allele frequency and the environment. The principles are illustrated by identifying a set of populations of Lolium perenne for the study of temperature responses.

Skipping in a hybrid polyketide synthase. Evidence for ACP-to-ACP chain transfer.

A tetraketide synthase containing a loading module (LM), the extension modules erythromycin module 1, rapamycin module 2, and erythromycin module 2 (LM-Ery1-Rap2-Ery2-TE), when expressed in Saccharopolyspora erythraea strain JC2, produced as previously reported a mixture of tetraketide lactones (minor products) and triketide lactones (major products). Several alternative plausible mechanisms by which this "skipping" phenomenon might occur may be proposed. Site-directed mutagenesis of the ketosynthase (KS) and acylcarrier protein (ACP) domains in the interpolated module has shown that skipping within the hybrid PKS involves passage of the growing polyketide through the interpolated module, by direct ACP-to-ACP transfer of the polyketide chain.

Development of a distress inventory for cancer: preliminary results.

Context: Advances in cancer treatment have led to cure and prolongation of patients' lives; however associated psychosocial problems, including distress, can detrimentally affect patients' compliance with treatment and ultimately, their outcome. Symptom distress has been well addressed in many studies; however, psychological distress has only been quantified by using depression or anxiety scales/checklists or quality of life scales containing a distress sub scale/component or by the use of scales that are not psychological distress-specific.

Aims: The present study is an attempt to construct a psychological distress inventory for specific use with cancer patients.

An unusual case of haemophilia--a case report.

Haemophilia in a female is very rare. We report a case of haemophilia in a female with a male sex chromosome pattern.

Cutaneous manifestations of systemic cryptococcosis in immunosupressed patients.

Since its discovery 100 years ago, the encapsulated yeast Cryptococcus neoformans has been implicated in systemic infections of many immunocompromised patients and has been a leading cause of morbidity and mortality in AIDS patients. Clinical symptoms are often initially subtle or lacking. Cutaneous involvement often carries a dismal prognosis as it is usually a sign of dissemination.

The use of nucleic acid amplification techniques to increase the viral safety of blood.

Despite recent significant improvements in the viral safety of blood and blood products there remains a small risk of contamination mainly due to the existence of a window period before the appearance of antibodies. Nucleic acid amplification technologies (NAT) permit a direct detection of the viral genome itself with an extreme sensitivity and specificity, without depending anymore on the delayed appearance of antibodies. These technologies can be applied to detect most blood-borne viruses.

BG9719 (CVT-124), an A1 adenosine receptor antagonist, protects against the decline in renal function observed with diuretic therapy.

Background: Adenosine may adversely affect renal function via its effects on renal arterioles and tubuloglomerular feedback, but effects of adenosine blockade in humans receiving furosemide and ACE inhibitors is unknown.

Methods And Results: This was a randomized, double-blind, ascending-dose, crossover study evaluating 3 doses of BG9719 in 63 patients with congestive heart failure. Patients received placebo or 1 of 3 doses of BG9719 on 1 day and the same medication plus furosemide on a separate day.

Dermatoglyphics in 46, XY females.

Dermatoglyphics is known to be one of the best available diagnostic tools in genetic disorders. This paper aims to find out the diagnostic characteristic dermatoglyphic features in cytogenetically confirmed 46, XY female patients. The total number of patients studied (46, XY females) were 31 and the control consisted of 30 males and 30 females.

Deprivation and mortality: the implications of spatial autocorrelation for health resources allocation.

This paper aims at investigating whether the relationship between mortality and socio-economic deprivation is affected by the spatial autocorrelation of ecological data. A simple model is used in which mortality (all-ages and premature) is the dependent variable, and deprivation, morbidity and other socio-economic indicators are the explanatory variables. Deprivation is measured by the Townsend index; the other socio-economic variables are the median income, unequal income distribution (Gini coefficient) and population density.

The impact of low levels of amorphous material (<5%) on the blending characteristics of a direct compression formulation.

During the manufacture of tablets for registration stability studies, it was observed that blends manufactured using milled active frequently failed the blend content uniformity criteria (actual relative standard deviation (RSD) of 4-15%) at the prelubrication stage, whereas unmilled active batches were consistently giving very good blend uniformity results (RSD<3.5%). The addition of magnesium stearate dramatically improved the blending characteristics of the milled batches, suggesting that milling had altered the surface properties.

Alternative energy technologies.

Fossil fuels currently supply most of the world's energy needs, and however unacceptable their long-term consequences, the supplies are likely to remain adequate for the next few generations. Scientists and policy makers must make use of this period of grace to assess alternative sources of energy and determine what is scientifically possible, environmentally acceptable and technologically promising.

CTX-M-type extended-spectrum beta-lactamase that hydrolyzes ceftazidime through a single amino acid substitution in the omega loop.

Escherichia coli ILT-1, Klebsiella pneumoniae ILT-2, and K. pneumoniae ILT-3 were isolated in May 1999 in Paris, France, from a rectal swab of a hospitalized 5-month-old girl. These isolates had a clavulanic acid-inhibited substrate profile that included expanded-spectrum cephalosporins.

Acute hemodynamic effects of conivaptan, a dual V(1A) and V(2) vasopressin receptor antagonist, in patients with advanced heart failure.

Background: Arginine vasopressin may contribute to abnormalities in hemodynamics and fluid balance in heart failure through its actions on V(1A) (vascular and myocardial effects) and V(2) receptors (renal effects). Inhibiting the action of vasopressin may be beneficial in patients with heart failure.

Methods And Results: A total of 142 patients with symptomatic heart failure (New York Heart Association class III and IV) were randomized to double-blind, short-term treatment with conivaptan, a dual V(1a)/V(2) vasopressin receptor antagonist, at a single intravenous dose (10, 20, or 40 mg) or placebo.

In vivo selection of a target/efflux double mutant of Pseudomonas aeruginosa by ciprofloxacin therapy.

We report the emergence after 4 days of ciprofloxacin monotherapy of a double mutant of Pseudomonas aeruginosa overexpressing the multidrug efflux system MexAB-OprM and harbouring a mutation in the gyrB gene. Compared with its initial susceptible counterpart, this mutant exhibited a significant increase in resistance to most of the beta-lactam antibiotics tested (16 x MIC of ticarcillin) and to ciprofloxacin (128 x MIC). Combined ceftazidime and amikacin therapy finally eradicated the resistant isolate and cured the patient of his infection.

Effects of omapatrilat on hemodynamics and safety in patients with heart failure.

Omapatrilat, a novel vasopeptidase inhibitor, is a highly potent and selective inhibitor of neutral endopeptidase and angiotensin-converting enzyme; its therapeutic potential is being investigated for treatment of hypertension and heart failure. In the present study, the safety, tolerability, and hemodynamic effects of single oral doses of omapatrilat (1 to 50 mg) are compared with placebo in patients with heart failure. Patients with heart failure (New York Heart Association functional class II to IV) and a resting left ventricular ejection fraction < or = 40% were enrolled in a double-blind, placebo-controlled, sequential-panel study of single doses of omapatrilat of 1, 2.

Novel propargylamine-linked nucleosides for high throughput SNP genotyping by MALDI-TOF MS.

The synthesis of positively charged and mass tagged nucleosides containing a quaternary ammonium functionality within the penultimate position of a primer is described. Neutralization of the sugar/thiophosphate backbone by alkylation increases the detection sensitivity in the mass spectrometric analysis by a factor of at least 100. The variable introduction of these novel compounds within the extension primers enables flexible design of multiplex genotyping reactions.

Linear IgA bullous dermatosis associated with vancomycin and disseminated varicella-zoster infection.

Linear IgA bullous dermatosis (LABD) is characterized by linear deposits of IgA at the basement membrane zone. Most cases are idiopathic, but medications, infections, autoimmune disorders, and malignancies have been documented as potential inducers. We report a case where both vancomycin and varicella-zoster infection were present as triggers.

Ends versus means: the role of markets in expanding access to contraceptives.

Achieving and sustaining universal access to contraceptives are key policy goals of interventions supplying contraceptive commodities. Donor support for contraceptive supplies is substantial and many public and national programmes rely on donated and subsidized supplies of contraceptives. Sustainability of programme benefits is a concern to both national governments and donor agencies.

Engineering a polyketide with a longer chain by insertion of an extra module into the erythromycin-producing polyketide synthase.

Background: Modular polyketide synthases catalyse the biosynthesis of medically useful natural products by stepwise chain assembly, with each module of enzyme activities catalysing a separate cycle of polyketide chain extension. Domain swapping between polyketide synthases leads to hybrid multienzymes that yield novel polyketides in a more or less predictable way. No experiments have so far been reported which attempt to enlarge a polyketide synthase by interpolating additional modules.

Mechanisms of macrolide resistance in clinical group B streptococci isolated in France.

Macrolide susceptibility was investigated in clinical group B streptococci obtained from neonates or pregnant women in 2000 in France. Of 490 consecutive isolates, 18% were resistant to erythromycin. The erm(B), erm(A) subclass erm(TR), and mef(A) genes were harbored by 47, 45, and 6% of these strains, respectively.

Molecular basis of Celmer's rules: role of the ketosynthase domain in epimerisation and demonstration that ketoreductase domains can have altered product specificity with unnatural substrates.

Background: Polyketides are structurally diverse natural products with a range of medically useful activities. Non-aromatic bacterial polyketides are synthesised on modular polyketide synthase multienzymes (PKSs) in which each cycle of chain extension requires a different 'module' of enzymatic activities. Attempts to design and construct modular PKSs that synthesise specified novel polyketides provide a particularly stringent test of our understanding of PKS structure and function.

Genetic characterization of Puumala hantavirus strains from Belgium: evidence for a distinct phylogenetic lineage.

Puumala hantavirus (PUUV) sequences were recovered from red bank voles (Clethrionomys glareolus) trapped between 1996 and 1998 in four localities of southern Belgium: Thuin, Montbliart, Momignies and Couvin. In addition, three PUUV isolates originating from bank voles trapped in the 1980s in southern (Montbliart) and northern (Turnhout) Belgium were genetically characterized. Analysis of the complete S and partial M segment sequences showed that the Belgian PUUV strains constitute a genetic lineage, distinct from other known PUUV lineages from Europe and Japan.