Genetic variation within the histamine pathway among patients with asthma – a pilot study

Objective: Histamine is an important mediator in the pathophysiology of asthma. We have previously reported that HRH1 is differentially expressed among those with asthma compared to those without asthma. Single histamine-related genes have also been associated with asthma. We aimed to evaluate known single nucleotide polymorphisms (SNPs) in genes along the histamine biotransformation and response pathway, and determine their association with asthma and HRH1 mRNA expression. Methods: We enrolled children and adults (n?=?93) with/without asthma who met inclusion/exclusion criteria. Genotyping was performed for nine known SNPs in the HDC, HRH1, HRH4, HNMT and ABP1 genes. HRH1 mRNA expression was determined on RNA from buccal tissue. General linear model, Fisher’s exact test and Chi-square test were used to determine differences in allele, genotype and haplotype frequency between subjects with and without asthma and differential HRH1 mRNA expression relative to genotype. Statistical significance was determined by p?<?0.05. Results: No difference was observed in genotype/allele frequency for the nine SNPs between subjects with and without asthma. The HNMT-1639C/-464C/314C/3′UTRA haplotype was more frequently observed in those without asthma than those with asthma (p?=?0.03). We also observed genetic differences relative to race and gender. HNMT 314 genotype CT was more frequent in males with asthma compared to those without asthma (p?=?0.04). Conclusions: Histamine pathway haplotype was associated with a diagnosis of asthma in our cohort but allele and genotype were not. Subgroup evaluations may also be important. Further studies are needed to determine the potential biological/clinical significance of our findings.     

Detachable cheek plumpers with different attachments for improving esthetics in a conventional complete denture: A clinical report

Aging is associated with loss of teeth, resorption of the alveolar process, and reduced tonicity of the facial muscles, leading to sunken cheeks and an unesthetic appearance. Esthetics in patients in need of complete dentures can be improved with the help of cheek plumpers to support the cheeks. They are noninvasive and straightforward to fabricate. Despite the reported success with the sole use of maxillary cheek plumpers, in certain situations, maxillary cheek plumpers provide inadequate support to the cheeks, evident in the lower third of the face. This clinical report describes a technique for fabricating detachable mandibular and maxillary cheek plumpers with 2 different types of attachment mechanisms.     

NLRP7 variants in spontaneous abortions with multilocus imprinting disturbances from women with recurrent pregnancy loss

Journal of Assisted Reproduction and Genetics - Comparative analysis of multilocus imprinting disturbances (MLIDs) in miscarriages from women with sporadic (SPL) and recurrent pregnancy loss (RPL)...     

First pass of an MR susceptibility contrast agent through normal and ischemic heart: Gradient-recalled echo-planar imaging

Gradient-recalled echo-planar magnetic resonance (MR) imaging was used to monitor the first pass of a magnetic susceptibility contrast agent through the heart of normal rats and rats subjected to 60-minute occlusion of the anterior branch of the left main coronary artery. Each animal (six normal and six ischemic) received four doses (0.05, 0.1, 0.15, and 0.2 mmol/kg) of Dy-DTPA-BMA [diethylenetriaminepentaacetic acid–bis(methylamide)] administered as a bolus volume of 1.0 mL/kg. In both normal and ischemic rats, signal intensity in nonischemic myocardium was reduced by the contrast agent in a dose-dependent manner. Signal intensity in the ischemic zone was reduced much less, so that at a contrast agent dose of 0.1 mmol/kg or greater the ischemic zone was clearly defined as a high-intensity zone on echo-planar images. Plots of the change in the apparent T2* relaxation rate (ΔR2*) during the peak bolus effect versus injected dose were well fit by straight lines for normal, nonischemic, and ischemic myocardium but not for blood in the left ventricle. No difference was seen between myocardial response in normal animals and in nonischemic regions in animals with coronary artery occlusion. These findings suggest that the contrast agent–induced changes in tissue T2* are monoexponential and support the idea that data derived from contrast transit studies may be useful for calculation of myocardial blood flow.     

Target-specific PIP2 signalling: how might it work?

Phosphatidylinositol 4,5-bisphosphate (PIP₂)-mediated signalling is a new and rapidly developing area in the field of cellular signal transduction. With the extensive and growing list of PIP₂-sensitive membrane proteins (many of which are ion channels and transporters) and multiple signals affecting plasma membrane PIP₂ levels, the question arises as to the cellular mechanisms that confer specificity to PIP₂-mediated signalling. In this review we critically consider two major hypotheses for such possible mechanisms: (i) clustering of PIP₂ in membrane microdomains with restricted lateral diffusion, a hypothesis providing a mechanism for spatial segregation of PIP₂ signals and (ii) receptor-specific buffering of the global plasma membrane PIP₂ pool via Ca²⁺-mediated stimulation of PIP₂ synthesis or release, a concept allowing for receptor-specific signalling with free lateral diffusion of PIP₂. We also discuss several other technical and conceptual intricacies of PIP₂-mediated signalling.