Spectral domain optical coherence tomography in mouse models of retinal degeneration.

Purpose: Spectral domain optical coherence tomography (SD-OCT) allows cross-sectional visualization of retinal structures in vivo. Here, the authors report the efficacy of a commercially available SD-OCT device to study mouse models of retinal degeneration.

Methods: C57BL/6 and BALB/c wild-type mice and three different mouse models of hereditary retinal degeneration (Rho(-/-), rd1, RPE65(-/-)) were investigated using confocal scanning laser ophthalmoscopy (cSLO) for en face visualization and SD-OCT for cross-sectional imaging of retinal structures.

Serum C-reactive protein in the differential diagnosis of ovarian masses.

Objective: A number of serum tumor markers have been investigated to aid clinicians in the differential diagnosis of ovarian masses. Serum C-reactive protein (CRP) is a widely used biomarker of inflammation and has been previously shown to be a promising biomarker in patients with ovarian cancer.

Study Design: In a retrospective single-center study, we evaluated serum CRP in 576 patients with benign and in 242 patients with malignant (ovarian tumors of low malignant potential [LMP]: n=44, epithelial ovarian cancer [EOC]: n=198) ovarian masses.

Retinal neuroprotection by hypoxic preconditioning is independent of hypoxia-inducible factor-1 alpha expression in photoreceptors.

Hypoxic preconditioning stabilizes hypoxia-inducible factor (HIF) 1 alpha in the retina and protects photoreceptors against light-induced cell death. HIF-1 alpha is one of the major transcription factors responding to low oxygen tension and can differentially regulate a large number of target genes. To analyse whether photoreceptor-specific expression of HIF-1 alpha is essential to protect photoreceptors by hypoxic preconditioning, we knocked down expression of HIF-1 alpha specifically in photoreceptor cells, using the cyclization recombinase (Cre)-lox system.

Molecular recognition of histone lysine methylation by the Polycomb group repressor dSfmbt.

Polycomb group (PcG) proteins repress transcription by modifying chromatin structure in target genes. dSfmbt is a subunit of the Drosophila melanogaster PcG protein complex PhoRC and contains four malignant brain tumour (MBT) repeats involved in the recognition of various mono- and dimethylated histone peptides. Here, we present the crystal structure of the four-MBT-repeat domain of dSfmbt in complex with a mono-methylated histone H4 peptide.

[Socioeconomic relevance of the idiopathic restless legs syndrome (RLS) in Germany: cost-of-illness study].

Background And Purpose: 1.3% of German adults suffer from clinically relevant restless legs syndrome (RLS). A cost-of-illness study was conducted to evaluate the costs for diagnosis and therapy of the idiopathic RLS.

Cooperative phagocytes: resident microglia and bone marrow immigrants remove dead photoreceptors in retinal lesions.

Phagocytosis is essential for the removal of photoreceptor debris following retinal injury. We used two mouse models, mice injected with green fluorescent protein-labeled bone marrow cells or green fluorescent protein-labeled microglia, to study the origin and activation patterns of phagocytic cells after acute blue light-induced retinal lesions. We show that following injury, blood-borne macrophages enter the eye via the optic nerve and ciliary body and soon migrate into the injured retinal area.

Fibrinogen plasma levels are an independent prognostic parameter in patients with cervical cancer.

Objective: The purpose of this study was to evaluate the association between fibrinogen plasma levels on disease-free patients and overall survival in patients with cervical cancer.

Study Design: Pretherapeutic fibrinogen plasma levels were examined in 313 patients with cervical cancer who were treated at the Department of Obstetrics and Gynecology, Medical University of Vienna. Fibrinogen plasma levels were correlated with clinical-pathologic findings and patient survival.

Life and death of sensory hair cells expressing constitutively active TRPML3.

The varitint-waddler mutation A419P renders TRPML3 constitutively active, resulting in cationic overload, particularly in sustained influx of Ca(2+). TRPML3 is expressed by inner ear sensory hair cells, and we were intrigued by the fact that hair cells are able to cope with expressing the TRPML3(A419P) isoform for weeks before they ultimately die. We hypothesized that the survival of varitint-waddler hair cells is linked to their ability to deal with Ca(2+) loads due to the abundance of plasma membrane calcium ATPases (PMCAs).

The prognostic value of four interleukin-1 gene polymorphisms in Caucasian women with breast cancer: a multicenter study.

Background: The proinflammatory cytokine interleukin-1 (IL-1) is known to play an important role in the carcinogenesis of breast cancer. Although IL-1 gene polymorphisms were reported to be associated with increased risk of breast cancer, their influence on survival of Caucasian breast cancer patients remains to be shown.

Methods: We studied the influence of four common gene polymorphisms (IL1A -889C/T, IL1B -511C/T, IL1B +3953E1/E2, and IL1RN long/2) of the IL-1 family on survival in 262 Caucasian patients with breast cancer by univariate and multivariate survival analysis.

In conditions of limited chromophore supply rods entrap 11-cis-retinal leading to loss of cone function and cell death.

RPE65 is a retinoid isomerase required for the production of 11-cis-retinal, the chromophore of both cone and rod visual pigments. We recently established an R91W knock-in mouse strain as homologous animal model for patients afflicted by this mutation in RPE65. These mice have impaired vision and can only synthesize minute amounts of 11-cis-retinal.

Leukemia inhibitory factor extends the lifespan of injured photoreceptors in vivo.

Survival and death of photoreceptors in degenerative diseases of the retina is controlled by a multitude of genes and endogenous factors. Some genes may be involved in the degenerative process itself whereas others may be part of an endogenous defense system. We show in two models of retinal degeneration that photoreceptor death strongly induces expression of leukemia inhibitory factor (LIF) in a subset of Muller glia cells in the inner nuclear layer of the retina.

Endocervical cytobrush for the detection of cervical dysplasia before large loop excision of the transformation zone (LLETZ).

Background: We aimed to identify the number of histologically verified cervical intraepithelial neoplasia (CIN)/cervical cancer lesions detected by endocervical cytobrush (EC) which have been missed by repeat PAP smear and colposcopy before large loop excision of the transformation zone (LLETZ).

Patients And Methods: A retrospective cohort study of 1,676 consecutive patients in a colposcopy clinic undergoing repeat PAP smear, colposcopy, biopsy, and subsequent LLETZ.

Results: Data were available for 1,421 patients.

Preliminary findings regarding overweight and obesity in pediatric bipolar disorder.

Objective: Overweight/obesity is highly prevalent among adults with bipolar disorder and has been associated with illness severity. Little is known regarding overweight/obesity among youth with bipolar disorder.

Method: Subjects were 348 youths aged 7 to 17 years who met DSM-IV criteria for bipolar I or bipolar II disorder or study-operationalized criteria for bipolar disorder not otherwise specified and were enrolled in the Course and Outcome of Bipolar Illness in Youth study.

Nonessential role of beta3 and beta5 integrin subunits for efficient clearance of cellular debris after light-induced photoreceptor degeneration.

Purpose: During light-induced photoreceptor degeneration, large amounts of cellular debris are formed that must be cleared from the subretinal space. The integrins alphavbeta5 and alphavbeta3 are involved in the normal physiological process of phagocytosis in the retina. This study was conducted to investigate the question of whether the lack of beta5 and/or beta3 integrin subunits might influence the course of retinal degeneration and/or clearance of photoreceptor debris induced by acute exposure to light.

Structural basis for LEAFY floral switch function and similarity with helix-turn-helix proteins.

The LEAFY (LFY) protein is a key regulator of flower development in angiosperms. Its gradually increased expression governs the sharp floral transition, and LFY subsequently controls the patterning of flower meristems by inducing the expression of floral homeotic genes. Despite a wealth of genetic data, how LFY functions at the molecular level is poorly understood.

Regulation of muscle development by DPF3, a novel histone acetylation and methylation reader of the BAF chromatin remodeling complex.

Chromatin remodeling and histone modifications facilitate access of transcription factors to DNA by promoting the unwinding and destabilization of histone-DNA interactions. We present DPF3, a new epigenetic key factor for heart and muscle development characterized by a double PHD finger. DPF3 is associated with the BAF chromatin remodeling complex and binds methylated and acetylated lysine residues of histone 3 and 4.

The validity of complex breast cysts after surgery.

Background: Breast cysts are the most common cause of benign breast masses. Simple breast cysts do not need further evaluation, but complex breast cysts require additional assessment due to the potential presence of malignancy. However, these complex cysts have rarely been examined and quantified according to the associated cancer detection rate.

Compensatory increase in P/Q-calcium current-mediated synaptic transmission following chronic block of N-type channels.

Synaptic transmission is triggered by presynaptic calcium influx through voltage-gated calcium channels. Axon terminals of central neurons express a diverse set of homologous calcium channels, giving rise to P/Q-, N-, and R-type calcium currents. The relative contribution of these components to presynaptic calcium signalling is heterogeneous and incompletely understood.

Using hippocampal microRNA expression differences between mouse inbred strains to characterise miRNA function.

Micro-RNAs (miRNAs) are short, single-stranded, noncoding RNAs that are involved in the regulation of protein-coding genes at the level of messenger RNA (mRNA). They are involved in the regulation of numerous traits, including developmental timing, apoptosis, immune function, and neuronal development. To better understand how the expression of the miRNAs themselves is regulated, we looked for miRNA expression differences among four mouse inbred strains, A/J, BALB/cJ, C57BL/6J, and DBA/2J, in one tissue, the hippocampus.

Overexpression of RPGR leads to male infertility in mice due to defects in flagellar assembly.

Male infertility is one possible consequence of a group of disorders arising from dysfunction of cilia. Ciliopathies include primary ciliary dyskinesia, polycystic kidney disease, Usher syndrome, nephronophthisis, Bardet-Biedl syndrome, Alstrom syndrome, and Meckel-Gruber syndrome as well as some forms of retinal degenerations. Mutations in the retinitis pigmentosa GTPase regulator gene (RPGR) are best known for leading to retinal degeneration but have also been associated with ciliary dysfunctions affecting other tissues.

Immunotherapy of murine hepatocellular carcinoma by alpha-fetoprotein DNA vaccination combined with adenovirus-mediated chemokine and cytokine expression.

Most hepatocellular carcinomas (HCCs) express oncofetal alpha-fetoprotein (AFP). We and others have demonstrated efficient tumor control mediated by cellular immune responses in mice bearing subcutaneous tumors derived from the AFP-expressing murine HCC cell line Hepa 1-6 by DNA vaccination against AFP. In the present study, we examined AFP DNA vaccination in the AFP-expressing primary murine HCC model BW7756.

Substance use disorders among adolescents with bipolar spectrum disorders.

Objective: We set out to examine the prevalence and correlates of substance use disorders (SUD) in a large sample of adolescents with bipolar disorder (BP).

Methods: Subjects were 249 adolescents ages 12 to 17 years old who fulfilled DSM-IV criteria for bipolar I disorder [(BPI), n = 154], or bipolar II disorder [(BPII), n = 25], or operationalized criteria for BP not otherwise specified [(BP NOS), n = 70], via the Schedule for Affective Disorders and Schizophrenia for School-Aged Children (K-SADS). As part of the multi-site Course and Outcome of Bipolar Youth study, demographic, clinical, and family history variables were measured via intake clinical interview with the subject and a parent/guardian.

Müller cell response to blue light injury of the rat retina.

Purpose: In addition to photoreceptor degeneration, excessive light causes degenerative alterations in the inner retina and ganglion cell death. A disturbance in osmohomeostasis may be one causative factor for the alterations in the inner retina. Because Müller cells mediate inner retinal osmohomeostasis (mainly through channel-mediated transport of potassium ions and water), the authors investigated whether these cells alter their properties in response to excessive blue light.