Clinical and laboratory data on severe acute respiratory syndrome (SARS), particularly on the temporal progression of abnormal laboratory findings, are limited. We conducted a prospective study on the clinical, radiologic, and hematologic findings of SARS patients with pneumonia, who were admitted to National Taiwan University Hospital from March 8 to June 15, 2003. Fever was the most frequent initial symptom, followed by cough, myalgia, dyspnea, and diarrhea. Twenty-four patients had various underlying diseases. Most patients had elevated C-reactive protein (CRP) levels and lymphopenia. Other common abnormal laboratory findings included leukopenia, thrombocytopenia, and elevated levels of aminotransferase, lactate dehydrogenase, and creatine kinase. These clinical and laboratory findings were exacerbated in most patients during the second week of disease. The overall case-fatality rate was 19.7%. By multivariate analysis, underlying disease and initial CRP level were predictive of death.

The potential tumor suppressor protein prohibitin can prevent cell proliferation and this required its binding to the Rb protein. Prohibitin could repress the transcriptional activity of E2F family members and this required a part of the marked box region of E2F. The sub-cellular localization of prohibitin has been variously attributed to the mitochondria as well as the inner cell membrane.Here we show that a subset of prohibitin molecules are present in the nucleus where it co-localizes with the Rb protein. Deletion of a putative amino-terminal membrane-docking domain of prohibitin had no effect on its ability to suppress cell proliferation or inhibit E2F activity. Our experiments show that a 53 amino-acid stretch of E2F1 is sufficient for being targeted by prohibitin; fusion of this region to GAL4 -VP16 construct could make it susceptible to prohibitinmediated, but not Rb-mediated repression. Prohibitin, like Rb, could repress transcription from SV40 and major late promoters when recruited directly to DNA. Prohibitin mediated transcriptional repression required histone-deacetylase activity, but unlike Rb, additional corepressors like N-CoR are also involved. Repression by prohibitin correlates with histone deacetylation on promoters and this was reversed by IgM stimulation of cells; IgM did not affect Rb-mediated repression or deacetylation of the promoters. Prohibitin thus appears to repress E2F-mediated transcription utilizing different molecular mediators and facilitate channeling of specific signaling pathways to the cell cycle machinery.

E2F transcription factors play a major role in controlling mammalian cell cycle progression. We recently reported that a potential tumor suppressor, prohibitin, which interacts with retinoblastoma protein (Rb), regulates E2F function and this activity correlates with its growth-suppressive activity. We show here that prohibitin recruits Brg-1/Brm to E2F-responsive promoters, and that this recruitment is required for the repression of E2F-mediated transcription by prohibitin. Expression of a dominantnegative Brg-1 or Brm releases prohibitin-mediated repression of E2F and relieves prohibitin-mediated growth suppression. Although prohibitin associates with, and recruits, Brg-1 and Brm independently of Rb, prohibitin/Brg-1/Brm-mediated transcriptional repression requires Rb. A viral oncoprotein, SV40 large T antigen, can reverse prohibitin-mediated suppression of E2F-mediated gene transcription, and targets prohibitin through interruption of the association between prohibitin and Brg-1/Brm without affecting the prohibitin±E2F interaction. Keywords: Brg-1/Brm/E2F/prohibitin/SV40 T antigen IntroductionProhibitin is a potential tumor suppressor gene that has been linked to human cancers. The prohibitin gene encodes a protein of 275 amino acids that is highly evolutionarily conserved. The prohibitin gene is located at 17q21, close to the BRCA1 locus, and four mutations have been reported in a screen of 23 sporadic breast cancers, suggesting a role for prohibitin in breast cancer (Sato et al., 1992(Sato et al., , 1993. The prohibitin gene was originally cloned based on its anti-proliferative activity, causing cell cycle arrest at G 1 /S (McClung et al., 1992(McClung et al., , 1995Asamoto and Cohen, 1994;Ikonen et al., 1995;Dell'Orco et al., 1996;Coates et al., 1997). We recently reported that prohibitin physically interacts with E2F and regulates E2F function, and that this interaction is necessary for the growth-suppressive activity of prohibitin (Wang et al., 1999a,b).The E2F family of transcription factors plays a major role in regulating mammalian cell cycle progression and is involved in differentiation, transformation and apoptosis (Chellappan et al., 1991;Nevins, 1992Nevins, , 1998 Kaelin, 1995, 1996;Harbour and Dean, 2000;Muller and Helin, 2000). Many cellular genes required for progression through the S phase contain E2F-binding sites in their promoters, and E2F activity is essential for their expression (Adams and Kaelin, 1995). It has been established that the retinoblastoma protein (Rb) family of tumor suppressors interacts with E2F and regulates their function (Chellappan et al., 1991). Recent studies have shown that Rb represses E2F-mediated transcriptional activation through recruitment of chromatin-remodeling complexes, such as histone deacetylase (HDAC) and Brg-1/Brm (Dunaief et al., 1994;Brehm et al., 1998;.We have found that prohibitin interacts with all members of the Rb family (Wang et al., 1999a) and demonstrated important functional and mechanistic differences between Rb-and prohibitin-mediated ...

Interleukin 17 (IL-17) is a Th17 cytokine associated with inflammation, autoimmunity, and defense against some bacteria; it has been implicated in many chronic autoimmune diseases including psoriasis, multiple sclerosis, and systemic sclerosis. However, whether IL-17 plays a role in the pathogenesis of ankylosing spondylitis (AS) remains unclear. To analyze the content of IL-17 and IL-23 in the serum from patients with AS compared with health control subject, 50 patients with AS and 43 healthy volunteers were recruited. Serum IL-17 levels were examined by enzyme linked immunosorbent assay (ELISA). Statistic analyses were performed by SPSS 13.0. Results show that the serum IL-17 and IL-23 levels were significantly elevated in AS patients as compared with normal controls. Nevertheless, no associations of serum IL-17 and IL-23 levels with clinical and laboratory parameters were found; no significant difference regarding serum IL-17 and IL-23 levels was found between less active AS and more active AS. However, there was a strong positive association between the serum levels of IL-17 and IL-23 in the AS patients. Our results indicate increased serum IL-17 and IL-23 levels in AS patients, suggesting that this two cytokine may play critical roles in the pathogenesis of AS. Therefore, further studies are required to confirm this preliminary data.

Estrogen antagonists are universally employed in the breast cancer therapy, although antagonist therapy is limited by the inevitable development of cellular resistance. The molecular mechanisms by which these agents inhibit cellular proliferation in breast cancer cells are not fully defined. Recent studies have shown the involvement of the E2F pathway in tamoxifen-induced growth arrest. We show that an E2F repressor, prohibitin, and the chromatin modifiers Brg1/Brm are required for estrogen antagonist-mediated growth suppression through the estrogen receptor, and that their recruitment to native promoter-bound E2F is induced via a JNK1 pathway. In addition, we demonstrate major mechanistic differences among the signaling pathways initiated by estrogen, estrogen deprivation, and estrogen antagonists. Collectively, these findings suggest that the prohibitin/Brg1/Brm node is a major cellular target for estrogen antagonists, and thereby also implicate prohibitin/Brg1/Brm as potentially important targets for breast cancer therapy.

Upconversion nanoparticles (UCNPs) have been widely employed for tumor imaging using magnetic resonance imaging (MRI) and upconversion luminescence (UCL) imaging.

HIGHLIGHTS• A biomimetic nanoprobe was built with cancer cell membrane-coated and Gd 3+ -doped upconversion nanoparticles.• The nanoprobe could be applied to in vivo UCL/MRI/PET multimodality precise imaging and successfully differentiated MDA-MB-231 tumor models through in vivo tri-modality imaging, which may be used for breast cancer molecular classification.ABSTRACT Triple-negative breast cancer (TNBC) is a subtype of breast cancer in which the estrogen receptor and progesterone receptor are not expressed, and human epidermal growth factor receptor 2 is not amplified or overexpressed either, which make the clinical diagnosis and treatment very challenging. Molecular imaging can provide an effective way to diagnose TNBC. Upconversion nanoparticles (UCNPs), are a promising new generation of molecular imaging probes. However, UCNPs still need to be improved for tumor-targeting ability and biocompatibility.This study describes a novel probe based on cancer cell membrane-coated upconversion nanoparticles (CCm-UCNPs), owing to the low immunogenicity and homologous-targeting ability of cancer cell membranes, and modified multifunctional UCNPs. This probe exhibits excellent performance in breast cancer molecular classification and TNBC diagnosis through UCL/MRI/PET tri-modality imaging in vivo. By using this probe, MDA-MB-231 was successfully differentiated between MCF-7 tumor models in vivo. Based on the tumor imaging and molecular classification results, the probe is also expected to be modified for drug delivery in the future, contributing to the treatment of TNBC. The combination of nanoparticles with biomimetic cell membranes has the potential for multiple clinical applications.

Minimally invasive techniques have revolutionized the management of a variety of spinal disorders. The authors of this study describe a new instrument and a percutaneous technique for anterior odontoid screw fixation, and evaluate its safety and efficacy in the treatment of patients with odontoid fractures. Ten patients (6 males and 4 females) with odontoid fractures were treated by percutaneous anterior odontoid screw fixation under fluoroscopic guidance from March 2000 to May 2002. Their mean age at presentation was 37.2 years (with a range from 21 to 55 years). Six cases were Type II and four were Type III classified by the Anderson and D'Alonzo system. The operation was successfully completed without technical difficulties, and without any soft tissue complications such as esophageal injury. No neurological deterioration occurred. Satisfactory results were achieved in all patients and all of the screws were in good placement. After a mean follow-up of 15.7 months (range 10-25 months), radiographic fusion was documented for 9 of 10 patients (90%). Neither clinical symptoms nor screw loosening or breakage occurred. Our preliminary clinical results suggest that the percutaneous anterior odontoid screw fixation procedure using a new instrument and fluoroscopy is technically feasible, safe, useful, and minimally invasive.