Novel Lesional Transcriptional Signature Separates Atherosclerosis With and Without Diabetes in Yorkshire Swine and Humans.

[Figure: see text].

Effects of Serelaxin in Patients with Acute Heart Failure.

Background: Serelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure.

Methods: In this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 μg per kilogram of body weight per day) or placebo, in addition to standard care.

Proton Pump Inhibitors and Preeclampsia Risk Among 157 720 Women.

Preeclampsia is a hypertensive disorder of pregnancy with a high rate of maternal and neonatal morbidity and mortality. The only definite treatment is delivery. Preclinical investigations have identified proton pump inhibitors (PPIs), which are commonly used to treat reflux during pregnancy, as a potential treatment for preeclampsia.

Symptoms, Signs and Long-term Prognosis of Vertically Transmitted Chlamydia trachomatis Infections.

Background: Although Chlamydia trachomatis infection is common in pregnant women, such infections are rarely encountered in infants. To clarify the recognition of C. trachomatis infections in infants, we analyzed symptoms and signs of perinatally acquired chlamydial infection, together with its long-term prognosis in a large population-based patient series.

Probability of vertical transmission of estimated from national registry data.

Objectives: colonisation is common in pregnant women, and it has been claimed that mother-to-child transmission may occur in 10%-70% of deliveries. infections are nevertheless rarely encountered in infants in clinical practice. In order to evaluate the reason for this discrepancy, we designed a nationwide study of the vertical transmission.

Nitric oxide is a potent inhibitor of the cbb(3)-type heme-copper oxidases.

C-type heme-copper oxidases terminate the respiratory chain in many pathogenic bacteria, and will encounter elevated concentrations of NO produced by the immune defense of the host. Thus, a decreased sensitivity to NO in C-type oxidases would increase the survival of these pathogens. Here we have compared the inhibitory effect of NO in C-type oxidases to that in the mitochondrial A-type.

Two C-methyl derivatives of [11C]WAY-100635--effects of an amido alpha-methyl group on metabolism and brain 5-HT1A receptor radioligand behavior in monkey.

Purpose: [carbonyl-11C]N-(2-(1-(4-(2-methoxyphenyl)-piperazinyl)ethyl)-N-pyridinyl)cyclohexanecarboxamide ([carbonyl-11C]WAY-100635) is an effective radioligand for imaging brain 5-HT1A receptors with positron emission tomography (PET). However, this radioligand has some drawbacks for deriving relative regional receptor densities, including rapid metabolism, which acts against accurate definition of an arterial input function for compartmental modeling, and very low nonspecific binding in brain, which detracts from the accuracy of modeling by a simplified reference tissue (cerebellum) approach. Here, in a search for a radioligand that overcomes these limitations, we investigated the effects of introducing a single methyl group at either of the carbon atoms alpha to the amide bond in [11C]WAY-100635.

Optimising the signal peptide for glycosyl phosphatidylinositol modification of human acetylcholinesterase using mutational analysis and peptide-quantitative structure-activity relationships.

Glycosyl phosphatidylinositol (GPI)-modified proteins have a C-terminal signal peptide (GPIsp) that mediates the addition of a GPI-anchor to an amino acid residue at the cleavage and modification site (omega-site). Within the GPIsp, a stretch of hydrophilic amino acid residues are found which constitutes the spacer region that separates the omega-site residue from a hydrophobic C-terminus. Deletions and insertions into the spacer region of human acetylcholinesterase (AChE) show that the length of this spacer region is very important for efficient GPI-modification.

The solution structure of the Leu22-->Val mutant AREA DNA binding domain complexed with a TGATAG core element defines a role for hydrophobic packing in the determination of specificity.

The seemingly innocuous leucine-to-valine mutation at position 22 of the AREA DNA binding domain results in dramatic changes in the in vivo expression profile of genes controlled by this GATA transcription factor. This is associated with a preference of the Leu22-->Val mutant for TGATAG sites over (A/C)GATAG sites. Quantitative gel retardation assays confirm this observation and show that the Leu22-->Val mutant AREA DNA binding domain has a approximately 30-fold lower affinity than the wild-type domain for a 13 base-pair oligonucleotide containing the wild-type CGATAG target.

The required dose of erythropoietin during renal anaemia treatment is related to the degree of impairment in erythrocyte deformability.

Background: Renal anaemia is rapidly corrected by recombinant human erythropoietin (rHuEpo) therapy, but the dose required varies greatly. Since impaired erythrocyte deformability may be one factor contributing to the development of renal anaemia, the interrelationship between that variable and the rHuEpo requirement was examined.

Methods: Twenty-five patients treated with hemodialysis and rHuEpo for at least 6 months were included in the study.

Additional peptidyl diazomethyl ketones, including biotinyl derivatives, which affinity-label calpain and related cysteinyl proteinases.

Calpain, the calcium-activated cysteinyl proteinase, can be irreversibly inactivated by peptidyl diazomethyl ketones in which the peptide portion contains a penultimate leucine residue. Some new derivatives of this type have been synthesized and examined for their rates of inactivation of chicken gizzard and human platelet calpain. Two derivatives containing a C-terminal biotin residue, Biot-Aca-Leu-TyrCHN2 and Biot-Aca-Leu-Leu-TyrCHN2, have also been prepared in the expectation that their application to the study of the function of calpain and related proteases will prove fruitful.

The properties of peptidyl diazoethanes and chloroethanes as protease inactivators.

Earlier work has demonstrated the irreversible inactivation of serine and cysteine proteinases by peptides with a C-terminal chloromethyl ketone group. With a C-terminal diazomethyl ketone, on the other hand, peptides become reagents specific for cysteine proteinases. We have now synthesized and examined the properties of reagents with an additional methyl side chain near the reactive grouping with the goal of diminishing side reactions in a cellular environment.