Search results for "Trans-Activators"
showing 10 items of 113 documents
Exclusion of the Sonic Hedgehog gene as responsible for Currarino syndrome and anorectal malformations with sacral hypodevelopment.
1999
Anorectal malformations (ARMs) are common congenital anomalies that account for 1:4 digestive malformations. ARM patients show different degrees of sacral hypodevelopment while the hemisacrum is characteristic of the Currarino syndrome (CS). Cases of CS present an association of ARM, hemisacrum and presacral mass. A gene responsible for CS has recently been mapped in 7q36. Among the genes localized in this critical region, sonic hedgehog (SHH) was thought to represent a candidate gene for CS as well as for ARM with different levels of sacral hypodevelopment according to its role in the differentiation of midline mesoderm. By linkage analysis we confirmed the critical region in one large fam…
Free [NADH]/[NAD+] regulates sirtuin expression
2011
Sirtuins are deacetylases involved in metabolic regulation and longevity. Our aim was to test the hypothesis that they are subjected to redox regulation by the [NADH]/[NAD(+)] ratio. We used NIH3T3 fibroblasts in culture, Drosophila fed with or without ethanol and exercising rats. In all three models an increase in [NADH]/[NAD(+)] came up with an increased expression of sirtuin mRNA and protein. PGC-1α (a substrate of sirtuins) protein level was significantly increased in fibroblasts incubated with lactate and pyruvate but this effect was lost in fibroblasts obtained from sirtuin-deficient mice. We conclude that the expression of sirtuins is subject to tight redox regulation by the [NADH]/[…
Clinicopathological and immunohistochemical analysis of 20 cases of Merkel cell carcinoma in search of prognostic markers.
2005
Aims: To evaluate the clinicopathological and immunohistochemical characteristics of Merkel cell carcinoma (MCC) in an attempt to find new, potentially significant, prognostic markers. Methods and results: Clinical data and follow-up, histopathological features (pattern, cell size, thickness, mitoses, vascular invasion, lymphocytic infiltration) and immunohistochemical detection [CK20, thyroid transcription factor (TTF-1), chromogranin A, synaptophysin, p53, Ki67, Fli-1, CD99, c-Kit] were evaluated in 20 cases of MCC. Fli-1 and CD99 were detected in 90% and 55% of cases, respectively. Tumour size > 30 mm, stage II, ‘absent’ lymphocytic infiltration, and the presence of > 50% of Ki67+ tumo…
Transgenic expression and activation of PGC-1α protect dopaminergic neurons in the MPTP mouse model of Parkinson’s disease
2011
Mitochondrial dysfunction and oxidative stress occur in Parkinson’s disease (PD), but little is known about the molecular mechanisms controlling these events. Peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) is a transcriptional coactivator that is a master regulator of oxidative stress and mitochondrial metabolism. We show here that transgenic mice overexpressing PGC-1α in dopaminergic neurons are resistant against cell degeneration induced by the neurotoxin MPTP. The increase in neuronal viability was accompanied by elevated levels of mitochondrial antioxidants SOD2 and Trx2 in the substantia nigra of transgenic mice. PGC-1α overexpression also protected against MP…
IL-6 receptor independent stimulation of human gp130 by viral IL-6.
2000
Abstract The genome of human herpes virus 8, which is associated with Kaposi’s sarcoma, encodes proteins with similarities to cytokines and chemokines including a homologue of IL-6. Although the function of these viral proteins is unclear, they might have the potential to modulate the immune system. For viral IL-6 (vIL-6), it has been demonstrated that it stimulates IL-6-dependent cells, indicating that the IL-6R system is used. IL-6 binds to IL-6R, and the IL-6/IL-6R complex associates with gp130 which dimerizes and initiates intracellular signaling. Cells that only express gp130 but no IL-6R cannot be stimulated by IL-6 unless a soluble form of the IL-6R is present. This type of signaling…
The photoperiod entrains the molecular clock of the rat pineal.
2005
The suprachiasmatic nucleus-pineal system acts as a neuroendocrine transducer of seasonal changes in the photoperiod by regulating melatonin formation. In the present study, we have investigated the extent to which the photoperiod entrains the nonself-cycling oscillator in the Sprague-Dawley rat pineal. For this purpose, the 24-h expression of nine clock genes (bmal1, clock, per1, per2, per3, cry1, cry2, dec1 and dec2) and the aa-nat gene was monitored under light-dark 8 : 16 and light-dark 16 : 8 in the rat pineal by using real-time RT-PCR. The 24-h pattern of the expression of only per1, dec2 and aa-nat genes was affected by photoperiod. In comparison with the short photoperiod, the durat…
Differential expression of suppressors of cytokine signaling-1, -2, and -3 in the rat hippocampus after seizure: implications for neuromodulation by …
2003
Numerous studies have investigated the expression of various cytokine families in the CNS after brain injury. The gp130 or interleukin (IL)-6-type cytokines have received a great deal of focus, and it is clear that they exhibit an acute and robust upregulation in various brain injury models. We are interested to determine, however, whether endogenously expressed cytokines in the CNS act in a direct neuromodulatory manner. In an accompanying study, we examined the expression of five gp130 cytokines and their receptors in the lithium-pilocarpine model of status epilepticus. We follow up that study here by trying to determine if gp130 signal transduction occurs in hippocampal principal neurons…
Functional characterization of Tat protein from human immunodeficiency virus. Evidence that Tat links viral RNAs to nuclear matrix.
1990
The processes of transcription and posttranscription are assumed to proceed in close association with the nuclear matrix. In this study we demonstrated that Tat, the trans-activating protein from human immunodeficiency virus type 1 (HIV-1), binds both to the TAR region of the nascent HIV mRNAs and the nuclear matrix with high affinity. Both North/Western blotting experiments and nitrocellulose binding studies revealed that Tat binds with an association constant (K alpha) of approximately 1 x 10(9) M-1 to the TAR segment of HIV RNA; binding of Tat to this sequence which is present between position 32 and 82 downstream from the TATA box was also confirmed by gel retardation assays. Binding of…
Identification of a novel activating mutation (Y842C) within the activation loop of FLT3 in patients with acute myeloid leukemia (AML).
2004
Fms-like tyrosine kinase 3 (FLT3) receptor mutations as internal tandem duplication (ITD) or within the kinase domain are detected in up to 35% of patients with acute myeloid leukemia (AML). N-benzoyl staurosporine (PKC412), a highly effective inhibitor of mutated FLT3 receptors, has significant antileukemic efficacy in patients with FLT3-mutated AML. Mutation screening of FLT3 exon 20 in AML patients (n = 110) revealed 2 patients with a novel mutation (Y842C) within the highly conserved activation loop of FLT3. FLT3-Y842C-transfected 32D cells showed constitutive FLT3 tyrosine phosphorylation and interleukin 3 (IL-3)-independent growth. Treatment with PKC412 led to inhibition of proliferat…
Control of murine cytomegalovirus in the lungs: Relative but not absolute immunodominance of the immediate-early 1 nonapeptide during the antiviral c…
1998
Effective control by the immune system is a hallmark of cytomegalovirus (CMV) infection. Accordingly, human CMV disease is a medical problem restricted to the immunologically immature or immunocompromised host (for a review, see reference 21). Murine models have implicated natural killer (NK) cells and CD8 T cells in the control of CMV infection. While NK cells mediate early protection in genetically resistant mouse inbred strains (4, 5, 31, 51), CD8 T cells establish enduring protective memory and function as principal antiviral effectors in susceptible strains (31). Specifically, in the BALB/c strain, major histocompatibility complex (MHC) class I-restricted antiviral CD8 T cells resolve …