Platelet-derived growth factor induces p21/WAF1 promoter in vascular smooth muscle cells via activation of an Sp1 site

AbstractMany studies suggested that cyclin-dependent kinase inhibitor (CDKI) p21 acts as a universal inhibitor of cyclin/CDK catalytic activity. This protein has also been shown to be a component of active cyclin/CDK complexes. In addition, it has recently been suggested that p21 serves as an assembly factor in platelet-derived growth factor (PDGF)-stimulated vascular smooth muscle cells (VSMC). However, little is known concerning the molecular mechanisms by which PDGF induces p21 gene expression in VSMC. In this report we demonstrate that PDGF induces the p21 expression at both the mRNA and protein levels. This increase in p21 gene expression was due to activation of the p21 promoter by PDGF. Through both deletion and mutation analysis of the p21 promoter, we defined a 10-bp sequence that is required for the activation of the p21 promoter by PDGF. In addition, gel shift and supershift assays demonstrated that this PDGF-responsive element binds specifically to the transcription factor Sp1. These results demonstrate that Sp1 mediates PDGF-induced p21 gene expression in VSMC. Moreover, immunoblot and immonoprecipitation analysis showed that the level of hyperphosphorylated retinoblastoma protein (Rb) is increased and the protein is physically associated with Sp1 in PDGF-treated cells, indicating that phosphorylated Rb may play a role in regulating Sp1 to activate p21 expression

Dependence of reaction center-type energy-dependent quenching on photosystem II antenna size

AbstractThe effects of photosystem II antenna size on reaction center-type energy-dependent quenching (qE) were examined in rice plants grown under two different light intensities using both wild type and qE-less (OsPsbS knockout) mutant plants. Reaction center-type qE was detected by measuring non-photochemical quenching at 50 μmol photons m−2 s−1 white light intensity. We observed that in low light-grown rice plants, reaction center-type qE was higher than in high light-grown plants, and the amount of reaction center-type qE did not depend on zeaxanthin accumulation. This was confirmed in Arabidopsis npq1–2 mutant plants that lack zeaxanthin due to a mutation in the violaxanthin de-epoxidase enzyme. Although the electron transport rate measured at a light intensity of 50 μmol photons m−2 s−1 was the same in high light- and low light-grown wild type and mutant plants lacking PsbS protein, the generation of energy-dependent quenching was completely impaired only in mutant plants. Analyses of the pigment content, Lhcb proteins and D1 protein of PSII showed that the antenna size was larger in low light-grown plants, and this correlated with the amount of reaction center-type qE. Our results mark the first time that the reaction center-type qE has been shown to depend on photosystem II antenna size and, although it depends on the existence of PsbS protein, the extent of reaction center-type qE does not correlate with the transcript levels of PsbS protein. The presence of reaction center-type energy-dependent quenching, in addition to antenna-type quenching, in higher plants for dissipation of excess light energy demonstrates the complexity and flexibility of the photosynthetic apparatus of higher plants to respond to different environmental conditions

A Spinal Cord Astrocytoma and Its Concurrent Osteoblastic Metastases at the Time of the Initial Diagnosis: a Case Report and Literature Review

Bone metastasis from a spinal cord astrocytoma has been reported only twice in the English medical literature. It is generally known that bone metastasis is found after the initial diagnosis with/without intervening surgery rather than being found at the time of the diagnosis of astrocytoma. The purpose of this article is to report for the first time a case of concurrent bone metastasis from a spinal cord astrocytoma at the time of diagnosing the spinal cord astrocytoma

Identification of the early and late responder genes during the generation of induced pluripotent stem cells from mouse fibroblasts

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Post-traumatic Back Pain Revealed as Tuberculous Spondylitis -A Case Report-

Tuberculous spondylitis is a very rare disease, but it can result in bone destruction, kyphotic deformity, spinal instability, and neurologic complications unless early diagnosis and proper management are done. Because the most common symptom of tuberculous spondylitis is back pain, it can often be misdiagnosed. Atypical tuberculous spondylitis can be presented as a metastatic cancer or a primary vertebral tumor. We must make a differential diagnosis through adequate biopsy. A 30-year-old man visited our clinic due to back and chest pain after a recent traffic accident. About 1 year ago, he had successfully recovered from tuberculous pleurisy after taking anti-tuberculosis medication. We performed epidural and intercostal blocks but the pain was not relieved. For the further evaluation, several imaging and laboratory tests were done. Finally, we confirmed tuberculous spondylitis diagnosis with the biopsy results

Triptolide-Mediated Apoptosis by Suppression of Focal Adhesion Kinase through Extrinsic and Intrinsic Pathways in Human Melanoma Cells

Triptolide (TPL) has been shown to inhibit cell proliferation and induce apoptosis in various human cancer cells; however, the precise mechanism of apoptosis induced by TPL in human melanoma cells has not yet been elucidated. In this study, we investigated the precise mechanism underlying cytocidal effects of TPL on human melanoma cells. Treatment of human melanoma cells with TPL significantly inhibited cell growth and induced apoptosis, as evidenced by flow cytometry and annexin V-fluorescein isothiocyanate analyses. TPL increased the levels of Fas and Fas-associated death domain (FADD) and induced cleavage of Bid by activation of caspase-8 and cytochrome c release from mitochondria to the cytosol, which resulted in activation of caspase-9 and caspase-3. Moreover, TPL-induced apoptosis in SK-MEL-2 cells was mediated through dephosphorylation of focal adhesion kinase (FAK) and its cleavage by caspase-8-mediated caspase-3 activation via upregulation of Fas expression. We also found that TPL mediated the dissociation of receptor-interacting protein (RIP) from FAK and enhanced the formation of RIP/Fas complex formation initiating cell death. In conclusion, our data firstly demonstrated that TPL induces apoptosis by both extrinsic and intrinsic apoptosis pathways in human melanoma cells and identified that RIP shuttles between Fas and FAK to mediate apoptosis

Amnesia and Pain Relief after Cardiopulmonary Resuscitation in a Cancer Pain Patient: A Case Report

The mechanism of chronic pain is very complicated. Memory, pain, and opioid dependence appear to share common mechanism, including synaptic plasticity, and anatomical structures. A 48-yr-old woman with severe pain caused by bone metastasis of breast cancer received epidural block. After local anesthetics were injected, she had a seizure and then went into cardiac arrest. Following cardiopulmonary resuscitation, her cardiac rhythm returned to normal, but her memory had disappeared. Also, her excruciating pain and opioid dependence had disappeared. This complication, although uncommon, gives us a lot to think about a role of memory for chronic pain and opioid dependence

Rate of Isolation and Trends of Antimicrobial Resistance of Multidrug Resistant Pseudomonas Aeruginosa from Otorrhea in Chronic Suppurative Otitis Media

ObjectivesTo assess the rate of isolation of Pseudomonas aeruginosa (PA) and multidrug-resistant PA (MDR-PA) from patients with chronic suppurative otitis media (CSOM) otorrhea and the annual trend of antibiotic-resistance.MethodsOtorrhea samples were collected aseptically from 1,598 CSOM patients. The rate of bacterial isolation and the results of antibiotic susceptibility testing were evaluated retrospectively.ResultsThe PA isolation rate from CSOM otorrhea was 24.4%. Of the 398 isolated strains tested for their susceptibilities to 10 antibiotics, 395 strains showed definitive results. Of these, 183 (46.3%) were susceptible to whole antibiotics and 212 (53.7%) was resistant to more than 1 antibiotics, with the frequency of antibiotics-resistance increasing significantly over time. Although strains susceptible to all antibiotics decreased over time, the rate of isolation of MDR-PA did not change significantly. Resistance to aminoglycosides and quinolones was higher than to other antibiotics and significantly increased over time, whereas resistance to other antibiotics showed no trend.ConclusionMDR-PA, assessed using five individual antibiotics and six antibiotic-classes, showed no tendency to increase or decrease over time. This may have been due to increased concern about antibiotic-resistant bacterial strains, leading to improved infection control within hospitals and healthcare centers