Cardiomyocyte-specific deletion of the coxsackievirus and adenovirus receptor results in hyperplasia of the embryonic left ventricle and abnormalities of sinuatrial valves.

The coxsackievirus and adenovirus receptor (CAR), which mediates infection by the viruses most commonly associated with myocarditis, is a transmembrane component of specialized intercellular junctions, including the myocardial intercalated disc; it is known to mediate cell-cell recognition, but its natural function is poorly understood. We used conditional gene targeting to investigate the possible functions of CAR during embryonic development, generating mice with both germline and tissue-specific defects in CAR expression. Homozygous germline deletion of CAR exon 2 or cardiomyocyte-specific gene deletion at embryonic day 10 (E10) mediated by Cre recombinase expressed under the control of the cardiac troponin T promoter resulted in death by E12.

Oral therapy for rosacea.

This article will examine oral therapies utilized in the treatment of rosacea. Important topics include recognizing which types of rosacea can benefit from oral therapy and concerns regarding the emergence of bacterial resistance.

Loss of PECAM-1 function impairs alveolarization.

The final stage of lung development in humans and rodents occurs principally after birth and involves the partitioning of the large primary saccules into smaller air spaces by the inward protrusion of septae derived from the walls of the saccules. Several observations in animal models implicate angiogenesis as critical to this process of alveolarization, but all anti-angiogenic treatments examined to date have resulted in endothelial cell (EC) death. We therefore targeted the function of platelet endothelial cell adhesion molecule, (PECAM-1), an EC surface molecule that promotes EC migration and has been implicated in in vivo angiogenesis.

Bone morphogenetic protein 4 promotes pulmonary vascular remodeling in hypoxic pulmonary hypertension.

We show that 1 of the type II bone morphogenetic protein (BMP) receptor ligands, BMP4, is widely expressed in the adult mouse lung and is upregulated in hypoxia-induced pulmonary hypertension (PH). Furthermore, heterozygous null Bmp4(lacZ/+) mice are protected from the development of hypoxia-induced PH, vascular smooth muscle cell proliferation, and vascular remodeling. This is associated with a reduction in hypoxia-induced Smad1/5/8 phosphorylation and Id1 expression in the pulmonary vasculature.

Open sky Müller muscle-conjunctival resection in phenylephrine test-negative blepharoptosis patients.

Purpose: To assess the efficacy of Müller muscle-conjunctival resection in patients in whom the phenylephrine test was negative.

Methods: A non-randomized, prospective clinical trial was conducted on 20 eyelids of 15 consecutive patients with blepharoptosis who showed no change in the upper eyelid margin-reflex distance (MRD1) following instillation of topical phenylephrine. The technique used was open sky Müller muscle-conjunctival resection.

Congenital heart disease reminiscent of partial trisomy 2p syndrome in mice transgenic for the transcription factor Lbh.

Partial trisomy 2p syndrome includes a spectrum of congenital heart disease (CHD) that is characterized by complex malformations of the outflow and inflow tracts, defects in cardiac septation, heart position, as well as abnormal ventricular development. Lbh (limb-bud and heart) is a novel, highly conserved putative transcriptional regulatory protein, which displays a unique spatiotemporal gene expression pattern during early mouse heart development. Here we show that human LBH maps to chromosome 2p23, a genomic region related to CHD in partial trisomy 2p syndrome.

Characterization of Nfatc1 regulation identifies an enhancer required for gene expression that is specific to pro-valve endocardial cells in the developing heart.

Nfatc1 is an endocardial transcription factor required for development of cardiac valves. Herein, we describe identification and characterization of a tissue-specific enhancer in the first intron of murine Nfatc1 that activates a heterogenic promoter and directs gene expression in a subpopulation of endocardial cells of the developing heart: the pro-valve endocardial cells. This enhancer activity begins on embryonic day (E) 8.

Embryonic heart failure in NFATc1-/- mice: novel mechanistic insights from in utero ultrasound biomicroscopy.

Gene targeting in the mouse has become a standard approach, yielding important new insights into the genetic factors underlying cardiovascular development and disease. However, we still have very limited understanding of how mutations affect developing cardiovascular function, and few studies have been performed to measure altered physiological parameters in mouse mutant embryos. Indeed, although in utero lethality due to embryonic heart failure is one of the most common results of gene targeting experiments in the mouse, the underlying physiological mechanisms responsible for embryonic demise remain elusive.

Conservation of Sox4 gene structure and expression during chicken embryogenesis.

While mutations in Sox4, a member of the SRY-like HMG box gene family, have been associated with a variety of human disorders and embryonic defects in the mouse, the structure and developmental expression of Sox4 in the avian embryo has not been described. We have isolated and characterized the chicken Sox4 gene. The chicken Sox4 gene shows a high degree of sequence homology with the mouse and human Sox4 genes, particularly in the HMG-like DNA binding domain and at the carboxy terminus.

Fourier analysis of induced irregular astigmatism. Photorefractive keratectomy versus laser in situ keratomileusis in a bilateral cohort of hyperopic patients.

Purpose: To analyze corneal topographic data by Fourier analysis to determine differences in irregular astigmatism following spherical hyperopic correction by photorefractive keratectomy (PRK) or laser in situ keratomileusis (LASIK).

Setting: Department of Ophthalmology, St. Thomas' Hospital, London, United Kingdom.

An essential role of Bmp4 in the atrioventricular septation of the mouse heart.

Proper septation and valvulogenesis during cardiogenesis depend on interactions between the myocardium and the endocardium. By combining use of a hypomorphic Bone morphogenetic protein 4 (Bmp4) allele with conditional gene inactivation, we here identify Bmp4 as a signal from the myocardium directly mediating atrioventricular septation. Defects in this process cause one of the most common human congenital heart abnormalities, atrioventricular canal defect (AVCD).

Coronary anatomy in congenitally corrected transposition of the great arteries.

Background: The advent of double switch procedures for the treatment of transposition of the great arteries with L-looped ventricles, e.g. typical congenitally corrected transposition of the great arteries, has made delineation of the coronary artery anatomy in these hearts important.

New frontiers in molecular pediatric cardiology.

Numerous advances in understanding the molecular basis of congenital heart disease have been published in the past year. Highlights are reviewed, focusing on two major topics: genetic syndromes and cardiac organogenesis. Genetic syndromes are discussed in the context of complementary data from targeted mutations in animals and genetic mapping studies in humans.

Characterization of Notch receptor expression in the developing mammalian heart and liver.

Alagille syndrome (AGS) is an autosomal dominant disorder characterized by bile duct paucity along with cardiovascular, skeletal, and ophthalmologic defects. The identification of JAG1 as the AGS disease gene revealed the crucial role of the Notch signaling pathway in the development of multiple organ systems in humans. Patients with identical mutations in JAG1 demonstrate extreme clinical variability, suggesting that other factors may influence the severity of the developmental defects in this disorder.

Notch1 and Jagged1 expression by the developing pulmonary vasculature.

The molecular mechanisms of pulmonary vascular development are poorly understood. Cell-specific developmental pathways are influenced by cell-cell signaling. Notch signaling molecules are highly conserved receptors active in many cell-fate determination systems.

The interaction between acne vulgaris and the psyche.

Acne is the most common problem that presents to dermatologists. Because it causes visible disfiguring of the face, it produces a great deal of embarrassment, frustration, anger, and depression in patients. In addition, acne is most common in adolescence and young adulthood, a time when patients are least capable of coping with additional stress.

Congenital blepharoptosis: a literature review of the histology of levator palpebrae superioris muscle.

Purpose: To identify and summarize the available published literature describing histologic features of congenital blepharoptosis and to consider the evidence for its classification as either a dystrophy or a dysgenesis. A brief overview of etiologic factors is included to highlight the controversy surrounding the cause of the condition.

Methods: Online searches of the current medical literature were performed with the use of search engines provided in British University libraries.

Growth factors in corneal wound healing following refractive surgery: A review.

The first part of this review article aims to provide important basic definitions of growth factor terminology, and to put forward a model for understanding the role of growth factors in a wound healing context. In the second part of the paper, we review the literature on growth factors in the cornea, including that on changes associated with wound healing following refractive surgery in the epithelial, stromal, and endothelial layers. The role of growth factors in stromal removal, corneal neovascularization, corneal innervation and wound healing is considered.

Regulation of the murine Nfatc1 gene by NFATc2.

NFAT proteins play a key role in the inducible expression of cytokine genes in T lymphocytes. NFATc1 and NFATc2 are the predominant NFAT family members in the peripheral immune system. NFATc2 is found abundantly in the cytoplasm of resting T cells, whereas Nfatc1 expression is induced during T cell activation.