A complex with poly(A)-binding protein and EWS facilitates the transcriptional function of oncogenic ETS transcription factors in prostate cells.

The ETS transcription factor ERG is aberrantly expressed in approximately 50% of prostate tumors due to chromosomal rearrangements such as TMPRSS2/ERG. The ability of ERG to drive oncogenesis in prostate epithelial cells requires interaction with distinct coactivators, such as the RNA-binding protein EWS. Here, we find that ERG has both direct and indirect interactions with EWS, and the indirect interaction is mediated by the poly-A RNA-binding protein PABPC1.

Androgen signaling connects short isoform production to breakpoint formation at Ewing sarcoma breakpoint region 1.

Ewing sarcoma breakpoint region 1 () encodes a multifunctional protein that can cooperate with the transcription factor ERG to promote prostate cancer. The EWSR1 gene is also commonly involved in oncogenic gene rearrangements in Ewing sarcoma. Despite the cancer relevance of , its regulation is poorly understood.

Toll-like receptor 4 signaling activates ERG function in prostate cancer and provides a therapeutic target.

The gene fusion and subsequent overexpression of the ERG transcription factor occurs in ∼50% of prostate tumors, making it the most common abnormality of the prostate cancer genome. While ERG has been shown to drive tumor progression and cancer-related phenotypes, as a transcription factor it is difficult to target therapeutically. Using a genetic screen, we identified the toll-like receptor 4 (TLR4) signaling pathway as important for ERG function in prostate cells.

--A high-throughput screen identifies inhibitors of the interaction between the oncogenic transcription factor ERG and the cofactor EWS.

Aberrant expression of the transcription factor ERG is a key driving event in approximately one-half of all of prostate cancers. Lacking an enzymatic pocket and mainly disordered, the structure of ERG is difficult to exploit for therapeutic design. We recently identified EWS as a specific interacting partner of ERG that is required for oncogenic function.

Pedunculated, well differentiated liposarcoma of the oesophagus mimicking giant fibrovascular polyp.

We present a rare case of a big oesophageal liposarcoma causing dysphagia and weight loss in a 75-year-old patient. Endoscopically, a pedunculated lesion with subtotal obstruction of the oesophageal lumen had been detected and thoracoabdominal oesophageal resection with gastric sleeve reconstruction was performed. Surprisingly, a liposarcoma of the oesophagus was revealed on histopathological analysis, showing MDM2 overexpression.

"Trick or treat": the influence of incentives on developmental changes in feedback-based learning.

Developmental researchers have suggested that adolescents are characterized by stronger reward sensitivity than both children and younger adults. However, at this point, little is known about the extent to which developmental differences in incentive processing influence feedback-based learning. In this study, we applied an incentivized reinforcement learning task, in which errors resulted in losing money (loss condition), failure to gain money (gain condition), or neither (no-incentive condition).

Do unsutured second-degree perineal lacerations affect postpartum functional outcomes?

Background: To compare the postpartum pelvic floor function of women with sutured second-degree perineal lacerations, unsutured second-degree perineal lacerations, and intact perineums.

Methods: A prospective cohort of nurse-midwifery patients consented to mapping of genital trauma at birth and an assessment of postpartum pelvic floor outcomes. Women completed validated questionnaires for perineal pain and urinary and anal incontinence at 12 weeks postpartum and underwent physical examination to assess pelvic floor strength and anatomy at 6 weeks postpartum.

The latent phase of labor: diagnosis and management.

The latent phase of labor is complex and not completely understood by modern science. Studies often ignore evaluation of this phase of labor because determination of onset is subjective. In this article, the definition and time parameters of latent phase labor are discussed, and generalized distinctions between prelabor and labor are evaluated.

Body mass index, midwifery intrapartum care, and childbirth lacerations.

Weight status is an important determinant of many health indices. Data from a clinical trial on measures to lower genital tract trauma in vaginal birth were used for a secondary analysis. The goal was to describe the relationship of body mass index and pregnancy weight gain to clinical intrapartum care, infant birthweight, and genital tract trauma with vaginal birth.

Twelve years and more than 30,000 nurse-midwife-attended births: the Los Angeles County + University of Southern California women's hospital birth center experience.

This article describes the setting, policies, practices, and outcomes of the nurse-managed in-hospital birth center at Los Angeles County + University of Southern California Women's Hospital, where women are selected upon admission for birth center care. A retrospective review of available data was made; when compared with hospital records, the primary data source was found to be 96% accurate. Results of the review indicated that from 1981 to 1992, there were 36,410 birth center admissions and 30,311 births, all attended by nurse-midwives; no intrapartum maternal or fetal deaths occurred among all admissions.

Natural course of remission in IDDM during 1st yr after diagnosis.

Objective: To describe the natural course of clinical remission in insulin-dependent diabetes mellitus (IDDM) when insulin dose is minimized without loss of target glycemia and to identify factors that predict clinical remission.

Research Design And Methods: Ninety-five patients, who were placebo-treated control subjects in the Canadian-European multicenter randomized trial of cyclosporin A in recent-onset IDDM, were studied.

Results: The mean insulin dose decreased during the first months after diagnosis, with a nadir at 3 mo, when 27% of the patients did not require insulin to maintain target glycemia.

Analysis of 22 immunomodulatory substances for efficacy in low-dose streptozotocin-induced diabetes.

Of 22 immunomodulatory substances screened 12 were effective in modulating the course of hyperglycemia following low dose streptozotocin treatment. In this animal model diabetes is induced by administration of low doses of streptozotocin (30-40 mg/kg) body weight to male C57BL/6J/Bom, C57BL/KsJ and C3H/He/Bom mice on 5 consecutive days. Conventional immunosuppressants (azathioprine, cyclophosphamide) largely protected from diabetes development.

Suppression of low-dose streptozotocin-induced diabetes by immunomodulatory lectins.

The effect of immunomodulatory lectins on diabetes development following low-dose streptozotocin treatment in inbred mice was studied. All lectins administered had been shown previously to suppress immune reactivity. Among plant lectins concanavalin A but not Lens culinaris or wheat germ agglutinin partially suppressed hyperglycaemia following low-dose streptozotocin.

Cell mediated immunity to islet cells: lessons from animal studies.

As a pathogenic factor of type I (insulin-dependent) diabetes cell mediated immunity to pancreatic islet cells, i.e. lymphocytic insulitis has been studied in mice with spontaneous lupus-like autoimmune disease, in mice with experimentally induced immune dysregulation and in mice treated with multiple low doses of streptozotocin or with alloxan.

Correlation of islet cell antibodies and HLA-DR phenotypes with diabetes mellitus in adults.

In a cross-sectional study, sera of 81 adult diabetic in-patients were tested for the presence of pancreatic islet cell antibodies (ICA), both IgG and complement-fixing. All patients had been well controlled initially with oral hypoglycaemic agents and therefore had been classified as having Type 2 (non-insulin-dependent) diabetes. However, 14 were subsequently classified as Type 1 (insulin-dependent) because they became insulin-dependent within 2 months of diagnosis.

Induction of experimental autoimmune diabetes by low-dose streptozotocin treatment in genetically resistant mice.

We have studied the effect of suppressor cell elimination on the induction of experimental autoimmune diabetes in mouse strains which are normally low or intermediate responders to multiple low-dose streptozotocin treatment. BALB/c (low responder) and C57BL/6J (intermediate responder) mice received 70 mg cyclophosphamide/kg, 1 or 6 days before the onset of streptozotocin injections. Following cyclophosphamide treatment, BALB/c mice become susceptible to the diabetogenic effect of streptozotocin.