University of Medicine and Dentistry of New Jersey

About: University of Medicine and Dentistry of New Jersey is a based out in . It is known for research contribution in the topics: Population & Pregnancy. The organization has 14634 authors who have published 19610 publications receiving 1041794 citations.

1,25-Dihydroxyvitamin D 3 ameliorates Th17 autoimmunity via transcriptional modulation of interleukin-17A

Abstract: A new class of inflammatory CD4(+) T cells that produce interleukin-17 (IL-17) (termed Th17) has been identified, which plays a critical role in numerous inflammatory conditions and autoimmune diseases. The active form of vitamin D, 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], has a direct repressive effect on the expression of IL-17A in both human and mouse T cells. In vivo treatment of mice with ongoing experimental autoimmune encephalomyelitis (EAE; a mouse model of multiple sclerosis) diminishes paralysis and progression of the disease and reduces IL-17A-secreting CD4(+) T cells in the periphery and central nervous system (CNS). The mechanism of 1,25(OH)(2)D(3) repression of IL-17A expression was found to be transcriptional repression, mediated by the vitamin D receptor (VDR). Transcription assays, gel shifting, and chromatin immunoprecipitation (ChIP) assays indicate that the negative effect of 1,25(OH)(2)D(3) on IL-17A involves blocking of nuclear factor for activated T cells (NFAT), recruitment of histone deacetylase (HDAC), sequestration of Runt-related transcription factor 1 (Runx1) by 1,25(OH)(2)D(3)/VDR, and a direct effect of 1,25(OH)(2)D(3) on induction of Foxp3. Our results describe novel mechanisms and new concepts with regard to vitamin D and the immune system and suggest therapeutic targets for the control of autoimmune diseases.

Human general transcription factor IIH phosphorylates the C-terminal domain of RNA polymerase II

Abstract: Phosphorylation of the carboxy-terminal domain of the largest subunit of RNA polymerase II is believed to control the transition from transcription initiation to elongation. The general transcription factor IIH (TFIIH) contains a kinase activity capable of phosphorylating this domain. Factors that promote the association of RNA polymerase II with the preinitiation complex stimulate this activity. The transcription factor HE, which is required for the stable association of TFIIH with the preinitiation complex, affects the processivity of TFIIH kinase.

Sensorimotor training in virtual reality: a review.

Abstract: Recent experimental evidence suggests that rapid advancement of virtual reality (VR) technologies has great potential for the development of novel strategies for sensorimotor training in neurorehabilitation. We discuss what the adaptive and engaging virtual environments can provide for massive and intensive sensorimotor stimulation needed to induce brain reorganization.Second, discrepancies between the veridical and virtual feedback can be introduced in VR to facilitate activation of targeted brain networks, which in turn can potentially speed up the recovery process. Here we review the existing experimental evidence regarding the beneficial effects of training in virtual environments on the recovery of function in the areas of gait,upper extremity function and balance, in various patient populations. We also discuss possible mechanisms underlying these effects. We feel that future research in the area of virtual rehabilitation should follow several important paths. Imaging studies to evaluate the effects of sensory manipulation on brain activation patterns and the effect of various training parameters on long term changes in brain function are needed to guide future clinical inquiry. Larger clinical studies are also needed to establish the efficacy of sensorimotor rehabilitation using VR in various clinical populations and most importantly, to identify VR training parameters that are associated with optimal transfer to real-world functional improvements.

Outcomes of localized prostate cancer following conservative management.

Abstract: Context Most newly diagnosed prostate cancers are clinically localized, and major treatment options include surgery, radiation, or conservative management. Although conservative management can be a reasonable choice, there is little contemporary prostate-specific antigen (PSA)–era data on outcomes with this approach. Objective To evaluate the outcomes of clinically localized prostate cancer managed without initial attempted curative therapy in the PSA era. Design, Setting, and Participants A population-based cohort study of men aged 65 years or older when they were diagnosed (1992-2002) with stage T1 or T2 prostate cancer and whose cases were managed without surgery or radiation for 6 months after diagnosis. Living in areas covered by the Surveillance, Epidemiology, and End Results (SEER) program, the men were followed up for a median of 8.3 years (through December 31, 2007). Competing risk analyses were performed to assess outcomes. Main Outcome Measures Ten-year overall survival, cancer-specific survival, and major cancer related interventions. Results Among men who were a median age of 78 years at cancer diagnosis, 10-year prostate cancer-specific mortality was 8.3% (95% confidence interval [CI], 4.2%-12.8%) for men with well-differentiated tumors; 9.1% (95% CI, 8.3%-10.1%) for those with moderately differentiated tumors, and 25.6% (95% CI, 23.7%-28.3%) for those with poorly differentiated tumors. The corresponding 10-year risks of dying of competing causes were 59.8% (95% CI, 53.2%-67.8%), 57.2% (95% CI, 52.6%-63.9%), and 56.5% (95% CI, 53.6%-58.8%), respectively. Ten-year disease-specific mortality for men aged 66 to 74 years diagnosed with moderately differentiated disease was 60% to 74% lower than earlier studies: 6% (95% CI, 4%-8%) in the contemporary PSA era (1992-2002) compared with results of previous studies (15%-23%) in earlier eras (1949-1992). Improved survival was also observed in poorly differentiated disease. The use of chemotherapy (1.6%) or major interventions for spinal cord compression (0.9%) was uncommon. Conclusions Results following conservative management of clinically localized prostate cancer diagnosed from 1992 through 2002 are better than outcomes among patients diagnosed in the 1970s and 1980s. This may be due, in part, to additional lead time, overdiagnosis related to PSA testing, grade migration, or advances in medical care.

p53 regulates maternal reproduction through LIF

Abstract: The transcription factor p53 has been studied extensively as a tumour suppressor, but little is known about its normal physiological role. A study in mice now links normal p53 function to reproduction and fertility. A p53 deficiency results in poor implantation of embryos in female mice, low pregnancy rates and small litter sizes. In this role p53 acts by regulating LIF (leukaemia inhibitory factor), a cytokine involved in blastocyst implantation. This work raises the possibility that the normal function of p53 is important for the success of implantation particularly in women undergoing in vitro fertilization or embryo transfer, and suggests a potential strategy to improve implantation efficiency in women with recurrent implantation failure. The p53 gene has been extensively studied for its role in tumour prevention but little is known about its normal physiological function. A crucial role of this factor in fecundity and reproduction is now reported. Extensive studies have shown that p53 is important in tumour prevention1. However, little is known about its normal physiological function. Here we show that p53 is important in reproduction, in a gender-specific manner. Significant decreases in embryonic implantation, pregnancy rate and litter size were observed in matings with p53-/- female mice but not with p53-/- male mice. The gene encoding leukaemia inhibitory factor (LIF), a cytokine critical for implantation2, was identified as a p53-regulated gene that functions as the downstream mediator of this effect. p53 can regulate both basal and inducible transcription of LIF. Loss of p53 decreased both the level and function of LIF in uteri. Lower LIF levels were observed in the uteri of p53-/- mice than in those of p53+/+ mice, particularly at day 4 of pregnancy, when transiently induced high levels of LIF were crucial for embryonic implantation. This observation probably accounts for the impaired implantation of embryos in p53-/- female mice. Administration of LIF to pregnant p53-/- mice restored maternal reproduction by improving implantation. These results demonstrate a function for p53 in maternal reproduction through the regulation of LIF. Evidence is accumulating that p53 may have a similar function in humans.