The amino terminus of receptor activity modifying proteins is a critical determinant of glycosylation state and ligand binding of calcitonin receptor-like receptor.

The calcitonin receptor-like receptor (CRLR) can function as either a receptor for calcitonin gene-related peptide (CGRP) or for adrenomedullin (ADM), depending upon the coexpression of a novel family of single transmembrane proteins, which we have called receptor activity modifying proteins or RAMPs. RAMPs 1, 2, and 3 transport CRLR to the plasma membrane with similar efficiencies, however RAMP1 presents CRLR as a terminally glycosylated, mature glycoprotein and a CGRP receptor, whereas RAMPs 2 and 3 present CRLR as an immature, core glycosylated ADM receptor. Characterization of the RAMP2/CRLR and RAMP3/CRLR receptors in HEK293T cells by radioligand binding (125I-ADM as radioligand), functional assay (cAMP measurement), or biochemical analysis (SDS-polyacrylamide gel electrophoresis) revealed them to be indistinguishable, even though RAMPs 2 and 3 share only 30% identity.

Comparison of tissue harmonic imaging with contrast (sonicated albumin echocardiography and Doppler myocardial imaging for enhancing endocardial border resolution.

Endocardial resolution during 2-dimensional echocardiography is technically limited in at least 10% to 15% of patients. Recently, several ultrasound imaging innovations have been introduced that may improve endocardial resolution and decrease the proportion of technically difficult studies. This study compares tissue harmonic imaging, intravenous sonicated albumin, and Doppler myocardial imaging in patients with technically difficult echocardiograms.

Clinical applications of transpulmonary contrast echocardiography.

Background: The recent development of new fluorocarbon-based echocardiographic contrast agents that are capable of opacification of the left-sided cardiac chambers after intravenous injection is a major new advance in diagnostic cardiac imaging.

Methods And Results: This is a review article focusing on these novel contrast agents, new echocardiographic imaging techniques to optimize their efficacy, and their clinical applications. Specific clinical applications of these agents are (1) enhancement of endocardial border definition to improve assessment of regional and global left ventricular function, (2) myocardial perfusion imaging by intravenous contrast echocardiography, (3) augmentation of spectral and color flow Doppler images, and (4) tissue-specific targeting of microbubbles for delivery of therapeutic agents.

The CGRP receptor can couple via pertussis toxin sensitive and insensitive G proteins.

Swiss 3T3 cell lines were constructed co-expressing receptor activity modifying protein (RAMP) 1 with the calcitonin receptor-like receptor (CRLR), and showed 125I-calcitonin-gene-related peptide (CGRP) 1 binding indicative of a type I CGRP receptor. Application of CGRP1 led to an increase in cAMP, which in 2/5 cell lines was augmented following pertussis toxin (PTX) pre-treatment. In Xenopus oocytes, expression of RAMP1, which potentiates an endogenous CGRP receptor, led to constitutive activation of co-expressed GIRK potassium channels.

Heterodimerization is required for the formation of a functional GABA(B) receptor.

GABA (gamma-aminobutyric acid) is the main inhibitory neurotransmitter in the mammalian central nervous system, where it exerts its effects through ionotropic (GABA(A/C)) receptors to produce fast synaptic inhibition and metabotropic (GABA(B)) receptors to produce slow, prolonged inhibitory signals. The gene encoding a GABA(B) receptor (GABA(B)R1) has been cloned; however, when expressed in mammalian cells this receptor is retained as an immature glycoprotein on intracellular membranes and exhibits low affinity for agonists compared with the endogenous receptor on brain membranes. Here we report the cloning of a complementary DNA encoding a new subtype of the GABAB receptor (GABA(B)R2), which we identified by mining expressed-sequence-tag databases.

Digital echocardiography.

Continued improvement in the computer price-to-performance ratio and the adoption of international standards have enhanced the feasibility of completely digital echocardiographic laboratories that were initially described more than a decade ago. Digital archival has distinct advantages over analog recording, including improved laboratory efficiency, capability of side-by-side comparison of current and historical studies, streamlined image storage, and enhanced interinstitution image transfer. Studies have demonstrated that clinical and electronic image compression allows efficient storage of data, without affecting diagnostic accuracy.

Digital echocardiographic laboratory: where do we stand?

The transition to an all-digital echocardiographic laboratory has been slow despite the advantages of digital echocardiography, the dramatic improvement in computer technology, and the acceptance by all major vendors and professional organizations of the Digital Imaging and Communications in Medicine image-formatting standard. This review article examines some current issues in digital echocardiography, including types of digital output, disk versus network exchange, digital and clinical compression techniques, and the choice of image storage format. Although specific exceptions exist, we conclude that the optimal solution will be one based on a network exchange of formatted images that follow the Digital Imaging and Communications in Medicine standard, now available from several manufacturers.

Regional differences in action potential characteristics and membrane currents of guinea-pig left ventricular myocytes.

Regional differences in action potential characteristics and membrane currents were investigated in subendocardial, midmyocardial and subepicardial myocytes isolated from the left ventricular free wall of guinea-pig hearts. Action potential duration (APD) was dependent on the region of origin of the myocytes (P < 0.01, ANOVA).

Usefulness of isometric hand grip exercise in detecting coronary artery disease during dobutamine atropine stress echocardiography in patients with either stable angina pectoris or another type of positive stress test.

Dobutamine atropine stress echocardiography (DASE) detects coronary artery disease (CAD) by increasing myocardial oxygen demand causing ischemia. The sensitivity of the test for detection of CAD is reduced in patients with submaximal stress. We hypothesized that increasing cardiac work load by adding isometric exercise would improve the detection of ischemia during DASE.

RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor.

Calcitonin-gene-related peptide (CGRP) and adrenomedullin are related peptides with distinct pharmacological profiles. Here we show that a receptor with seven transmembrane domains, the calcitonin-receptor-like receptor (CRLR), can function as either a CGRP receptor or an adrenomedullin receptor, depending on which members of a new family of single-transmembrane-domain proteins, which we have called receptor-activity-modifying proteins or RAMPs, are expressed. RAMPs are required to transport CRLR to the plasma membrane.

Detection of myocardial perfusion defects by contrast echocardiography in the setting of acute myocardial ischemia with residual antegrade flow.

Although myocardial contrast echocardiography accurately demarcates area at risk during total coronary occlusion, the ability of MCE to delineate area at risk in the presence of residual antegrade flow is unknown. We hypothesized that perfusion defects in myocardial segments supplied by severe coronary stenoses with residual antegrade flow could be detected by MCE using intravenous FS069. We studied 13 open-chest dogs using an intravenous injection of FS069 during intermittent harmonic imaging.

Changes in subsarcolemmal sodium concentration measured by Na-Ca exchanger activity during Na-pump inhibition and beta-adrenergic stimulation in guinea-pig ventricular myocytes.

Measurement of Na-Ca exchange activity was used to examine subsarcolemmal sodium levels ([Na+]s) in single, voltage-clamped guinea-pig cardiac myocytes while Na-K pump activity was modulated pharmacologically. Changes in Nas were evaluated from phase-plane analysis of the changes in intracellular calcium, measured using the fluorescent indicators Fura-red and Fluo-3. Activation of beta-adrenoceptors with 1 microM isoprenaline resulted in activation of the cAMP-dependent chloride current, but had no effect on the calcium transient mediated via the Na-Ca exchanger, regardless of whether the Na-K pump was active or inhibited (with strophanthidin).

The determination of magnesium in human blood plasma by 31P magnetic resonance spectroscopy using a macrocyclic reporter ligand.

The ligand 1,4,7-triazacyclononane-1,4,7-tris(methylene methylphosphinic acid), NOTMP, was used to measure free MgII levels in blood plasma by 31P MRS. Separate resonances were observed for the free ligand and the MgII complex and the ratio of their resonance areas was used to evaluate the free, ionized MgII concentration, [Mg]free. The CaII and the ZnII complexes gave rise to separate resonances in the 31P spectrum in an aqueous sample.

Safety and efficacy of QW7437, a new fluorocarbon-based echocardiographic contrast agent.

The aim of this study was to evaluate the safety and efficacy of QW7437, a new fluorocarbon-based transpulmonary myocardial echocardiographic contrast agent. QW7437 is an anionically charged 2% dodecafluoropentane emulsion molecule, similar to EchoGen, a contrast agent previously shown to be efficacious in providing myocardial opacification by means of venous injection. This new agent has theoretical potential to provide greater safety and efficacy as a result of (1) reduced adherence to the negatively charged vascular endothelium and (2) reduced microbubble coalescence.

Relation of contractile reserve during low-dose dobutamine echocardiography and angiographic extent and severity of coronary artery disease in the presence of left ventricular dysfunction.

Contractile reserve, during low-dose dobutamine echocardiography, is frequently used for the assessment of myocardial viability in patients with coronary artery disease (CAD) and left ventricular (LV) dysfunction. Whether contractile reserve is affected by the severity of the underlying CAD is presently unknown. Accordingly, we studied 58 patients with stable CAD and LV dysfunction who underwent coronary angiography and low-dose dobutamine echocardiography.

Accuracy of dobutamine echocardiography for detection of myocardial viability in patients with an occluded left anterior descending coronary artery.

Objectives: We studied the accuracy of dobutamine echocardiography for the detection of myocardial viability in patients with an occluded left anterior descending coronary artery and regional ventricular dysfunction.

Background: Contractile reserve during dobutamine echocardiography is an accurate marker of myocardial viability in patients with coronary stenoses and ventricular dysfunction. However, its accuracy in patients with an occluded vessel has not been evaluated.

Introduction to the special section on attachment and psychopathology: 2. Overview of the field of attachment.

J. Bowlby (1969) proposed that the child's insistence on maintainance of proximity to protective (parental) figures was attributable to the activities of an attachment behavioral system which regulates primate safety and survival. M.

Comparison of IgG subclasses in foetal serum, maternal serum at delivery and milk in IgA-deficient and control women.

Immunoglobulin G subclass concentrations were measured in paired foetal (cord) and maternal serum specimens at delivery from 27 IgA-deficient (serum IgA < 0.01 g/l) and 15 control women. IgA-deficient women had significantly higher serum IgG1 and IgG3 concentrations than control women but 2 of the group had concomitant IgG2/IgG4 deficiency and a further 12 had low IgG4 concentrations (serum IgG4 < 0.

Fluspirilene block of N-type calcium current in NGF-differentiated PC12 cells.

1. High voltage-activated calcium currents were recorded in nerve growth factor (NGF)-differentiated PC12 cells with the whole-cell patch clamp technique. After exposure to NGF for 3-10 days the PC12 cells developed neurone-like processes and calcium currents which were pharmacologically separable into L- and N-types (defined by sensitivity to nifedipine and omega-conotoxin GVIA respectively).

Differences in the effects of tachykinin NK1 receptor antagonists: neuronal versus smooth muscle tissues.

The effects of three tachykinin NK1 receptor antagonists (L-668,169, (+/-)-RP 67580, and (+/-)-CP 96.345) were examined for their ability to antagonise responses evoked by substance P O-methyl ester (a selective NK1 receptor agonist) in isolated neuronal tissue (rat superior cervical ganglia and guinea-pig locus coeruleus) and smooth muscle tissues (rat urinary bladder and guinea-pig ileum longitudinal muscle/myenteric plexus). (+/-)-RP 67580 was similarly effective in antagonising responses in both rat superior cervical ganglia and urinary bladder (estimated pKa value = 7.

Information sharing concerning schizophrenia in a family member: adult siblings' perspectives.

Content analysis of 11 in-depth interviews of adult siblings having a brother or sister with schizophrenia shows a variation in families' needs and desire for information about the illness. Families who do not seek information appear to be in denial, whereas those who can be classified as withholding information realize the significance of illness but are reluctant to share information. Information provided by mental health professionals is thought to be scarce and frequently confusing.