Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals.

There is growing recognition that mammalian cells produce many thousands of large intergenic transcripts. However, the functional significance of these transcripts has been particularly controversial. Although there are some well-characterized examples, most (>95%) show little evidence of evolutionary conservation and have been suggested to represent transcriptional noise.

Transgenic mice with defined combinations of drug-inducible reprogramming factors.

Proviruses carrying drug-inducible Oct4, Sox2, Klf4 and c-Myc used to derive 'primary' induced pluripotent stem (iPS) cells were segregated through germline transmission, generating mice and cells carrying subsets of the reprogramming factors. Drug treatment produced 'secondary' iPS cells only when the missing factor was introduced. This approach creates a defined system for studying reprogramming mechanisms and allows screening of genetically homogeneous cells for compounds that can replace any transcription factor required for iPS cell derivation.

A comparison of personality disorder characteristics of patients with nonepileptic psychogenic pseudoseizures with those of patients with epilepsy.

We sought to determine the type of personality disorder cluster associated with patients with nonepileptic psychogenic seizures (NES) compared with that of patients with epileptic seizures (ES). Consecutive adult patients admitted for video/EEG monitoring found to have NES were compared with a simultaneously admitted patient with confirmed epilepsy. Personality was assessed using the Structured Clinical Interview for DSM-IV-TR Axis II Personality Disorders.

Reprogramming of murine and human somatic cells using a single polycistronic vector.

Directed reprogramming of somatic cells by defined factors provides a novel method for the generation of patient-specific stem cells with the potential to bypass both the practical and ethical concerns associated with somatic cell nuclear transfer (SCNT) and human embryonic stem (hES) cells. Although the generation of induced pluripotent stem (iPS) cells has proven a robust technology in mouse and human, a major impediment to the use of iPS cells for therapeutic purposes has been the viral-based delivery of the reprogramming factors because multiple proviral integrations pose the danger of insertional mutagenesis. Here we report a novel approach to reduce the number of viruses necessary to reprogram somatic cells by delivering reprogramming factors in a single virus using 2A "self-cleaving" peptides, which support efficient polycistronic expression from a single promoter.

Reprogramming of somatic cell identity.

All mammalian somatic cells originate from a single fertilized cell, the zygote, and share identical genetic information despite the dramatic changes in cell structure and function that accompany organismal development. The genome is subjected to a wide array of epigenetic modifications during lineage specification, a process that contributes to the implementation and maintenance of specific gene expression programs in somatic cells. Nuclear transfer and cell-fusion experiments demonstrate that the epigenetic signature directing a cell identity can be erased and modified into that of another cell type.

Familial pulmonary alveolar proteinosis caused by mutations in CSF2RA.

Primary pulmonary alveolar proteinosis (PAP) is a rare syndrome characterized by accumulation of surfactant in the lungs that is presumed to be mediated by disruption of granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling based on studies in genetically modified mice. The effects of GM-CSF are mediated by heterologous receptors composed of GM-CSF binding (GM-CSF-Ralpha) and nonbinding affinity-enhancing (GM-CSF-Rbeta) subunits. We describe PAP, failure to thrive, and increased GM-CSF levels in two sisters aged 6 and 8 yr with abnormalities of both GM-CSF-Ralpha-encoding alleles (CSF2RA).

Early steps of the virus replication cycle are inhibited in prostate cancer cells resistant to oncolytic vesicular stomatitis virus.

Vesicular stomatitis virus (VSV) is currently being studied as a candidate oncolytic virus for tumor therapies due to its potent tumoricidal activity. Previous studies have demonstrated that VSV selectively infects tumor cells due to defects in their antiviral pathways. These defects make them more susceptible to VSV-induced killing than normal cells.

Dynamics of molecular diffusion of rhodamine 6G in silica nanochannels.

We describe a method to study diffusion of rhodamine 6G dye in single silica nanochannels using arrays of silica nanochannels. Dynamics of the molecules inside single nanochannel is found from the change of the dye concentration in solution with time. A 10(8) decrease in the dye diffusion coefficient relative to water was observed.

Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency.

Pluripotent cells can be derived from fibroblasts by ectopic expression of defined transcription factors. A fundamental unresolved question is whether terminally differentiated cells can be reprogrammed to pluripotency. We utilized transgenic and inducible expression of four transcription factors (Oct4, Sox2, Klf4, and c-Myc) to reprogram mouse B lymphocytes.

The combined oxacillin resistance and coagulase (CORC) test for rapid identification and prediction of oxacillin resistance in Staphylococcus species directly from blood culture.

The combined oxacillin resistance and coagulase (CORC) protocol for rapid identification and determination of oxacillin-susceptibility in Staphylococcus spp from blood culture is described. It incorporates a modified direct tube coagulase test (TCT) and a novel 4-hour multiplication-induction step, which increases the expression of staphylococcal PBP2a if present, facilitating detection by a commercial PBP2a latex agglutination kit. The protocol shows excellent sensitivity and specificity for determination of coagulase-positivity in staphylococci from patient blood cultures (96.

The value of serum neopterin, interferon-gamma levels and interleukin-12B polymorphisms in predicting acute renal allograft rejection.

Acute rejection remains a poor predictor of graft outcome. In this study, we measured serum levels of interferon (IFN)-gamma and neopterin by enzyme-linked immunosorbent assay and a single nucleotide polymorphism (SNP) within the 3' untranslated region of the interleukin (IL)-12 B gene (1188 A/C) to determine whether either of these factors could predict acute rejection in renal transplantation. Significantly higher early post-transplant neopterin levels (days 5-7; 35.

Effect of stress on basophil function in chronic idiopathic urticaria.

Background: Chronic idiopathic urticaria (CIU) is a distressing skin condition involving recurrent itchy hives lasting 6 weeks or longer. The mechanism involves mast cell and basophil degranulation, which releases inflammatory mediators including histamine. In our clinical practice, we have observed that the onset of CIU is often preceded by a major life event.

A prospective analysis of long-term quality of life after permanent I-125 brachytherapy for localised prostate cancer.

Background And Purpose: To prospectively evaluate long-term urinary, bowel and sexual function after I-125 brachytherapy for localised prostate cancer using patient administered validated Quality of Life (QoL) instruments.

Materials And Methods: Between March 1995 and March 2004, 673 men underwent brachytherapy and recorded urinary symptoms prospectively using the International Prostate Symptom Score (IPSS). In addition, in a subgroup of 116 patients, the Expanded Prostate Cancer Index Composite (EPIC) was used to record QoL information on urinary, bowel and sexual function before treatment and at regular time intervals for at least two years.

BACE1 regulates voltage-gated sodium channels and neuronal activity.

BACE1 activity is significantly increased in the brains of Alzheimer's disease patients, potentially contributing to neurodegeneration. The voltage-gated sodium channel (Na(v)1) beta2-subunit (beta2), a type I membrane protein that covalently binds to Na(v)1 alpha-subunits, is a substrate for BACE1 and gamma-secretase. Here, we find that BACE1-gamma-secretase cleavages release the intracellular domain of beta2, which increases mRNA and protein levels of the pore-forming Na(v)1.

Recto-urethral fistula following brachytherapy for localized prostate cancer.

Objective: The use of prostate brachytherapy (BT) in the management of prostate cancer is increasing. BT is often chosen because of its perceived lower toxicity when compared with other radical therapy options. Rarely however serious complications can occur.

Medicare coverage of PET for cervical cancer.

Positron emission tomography (PET) with 2-[(18)F]fluoro-2-deoxyglucose (FDG) has had a major impact on the initial evaluation and follow-up of patients with cancer. Yet because Medicare coverage standards differ from the US Food and Drug Administration's approval requirements, FDG-PET has not been covered by the Centers for Medicare and Medicaid Service (CMS) for general oncologic indications. Instead, starting in 1995, CMS began to cover FDG-PET for specific cancers and indications after an individualized review of the evidence of benefit in the scientific literature.

The National Oncologic PET Registry: expanded medicare coverage for PET under coverage with evidence development.

Objective: The purpose of this article is to review the recent expansion of Medicare coverage for 18F-FDG PET for certain cancer indications under the Centers for Medicare & Medicaid Services' new Coverage with Evidence Development (CED) policy and to describe the specific operational mechanics of the National Oncologic PET Registry (NOPR).

Conclusion: The NOPR will make possible a more accurate assessment of the actual influence of PET on patient management across a wide spectrum of cancer indications. By linking access to PET for virtually all Medicare beneficiaries to the collection of clinically valuable evidence, the NOPR represents the cutting edge of the CED approach.

A sequential approach to the management of a massive intracoronary thrombus in ST elevation myocardial infarction: a case report.

Thrombus-laden coronary lesions present a particular challenge to the interventional cardiologist. Despite the development of multiple strategies to attack this problem, lesions with angio-graphically visible thrombus still carry a high risk of complications when coronary intervention is attempted. The authors present a case of acute inferior ST elevation myocardial infarction with a massive thrombus in an ectatic right coronary artery.

The current role of imaging for prostate brachytherapy.

Prostate brachytherapy is a radiotherapy technique for early stage prostate cancer that uses imaging guidance to place radioactive sources directly into the prostate gland. Transrectal ultrasound is used to facilitate a template-guided transperineal approach to the prostate and permits a highly conformal method of prostate radiotherapy with doses far higher than can be achieved with other radiation techniques. Maturing data has validated this technique as an acceptable treatment option with favourable and durable biochemical outcomes.

GM-CSF autoantibodies and neutrophil dysfunction in pulmonary alveolar proteinosis.

Background: Increased mortality from infection in patients with pulmonary alveolar proteinosis occurs in association with high levels of autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF). We tested the hypothesis that neutrophil functions are impaired in patients with pulmonary alveolar proteinosis and that GM-CSF autoantibodies cause the dysfunction.

Methods: We studied 12 subjects with pulmonary alveolar proteinosis, 61 healthy control subjects, and 12 control subjects with either cystic fibrosis or end-stage liver disease.

PU.1 redirects adenovirus to lysosomes in alveolar macrophages, uncoupling internalization from infection.

Adenovirus is endocytosed and efficiently destroyed by human and murine alveolar macrophages (AMs) and rapidly cleared from the lungs of wild-type but not GM-CSF(-/-) mice. We hypothesized that GM-CSF may regulate adenovirus clearance in AMs via the transcription factor PU.1 by redirecting virion trafficking from the nucleus to lysosomes.

Presenilin/gamma-secretase-mediated cleavage regulates association of leukocyte-common antigen-related (LAR) receptor tyrosine phosphatase with beta-catenin.

Leukocyte-common antigen-related (LAR) receptor tyrosine phosphatase regulates cell adhesion and formation of functional synapses and neuronal networks. Here we report that LAR is sequentially cleaved by alpha- and presenilin (PS)/gamma-secretases, which also affect signaling and/or degradation of type-I membrane proteins including the Alzheimer disease-related beta-amyloid precursor protein. Similar to the previously characterized PS/gamma-secretase substrates, inhibition of gamma-secretase activity resulted in elevated LAR C-terminal fragment (LAR-CTF) levels in stably LAR-overexpressing Chinese hamster ovary (CHO) cells, human neuroglioma cells, and mouse cortical neurons endogenously expressing LAR.

Side effects of permanent I125 prostate seed implants in 667 patients treated in Leeds.

Purpose: To report the side effects and complications after I-125 seeds prostate implant after 8.5 years experience.

Methods And Materials: Six hundred and sixty seven (667) patients were treated between March 1995 and December 2001.

Presenilin/gamma-secretase and alpha-secretase-like peptidases cleave human MHC Class I proteins.

HLA (human leucocyte antigen)-A2 is an MHC Class I protein with primary functions in T-cell development and initi-ation of immune cell responses. MHC I proteins also play roles in intercellular adhesion, apoptosis, cell proliferation and neuronal plasticity. By utilizing a sequence comparison analysis, we recently identified HLA-A2 as a potential substrate for the Alzheimer's disease-associated PS1 (presenilin 1)/gamma-secretase.