Diagnostic Accuracy of Cincinnati Pre-Hospital Stroke Scale

Introduction: Stroke is recognized as the third cause of mortality after cardiovascular and cancer diseases, so that lead to death of about 5 million people, annually. There are several scales to early prediction of at risk patients and decreasing the rate of mortality by transferring them to the stroke center. In the present study, the accuracy of Cincinnati pre-hospital stroke scale was assessed. Methods: This was a retrospective cross-sectional study done to assess accuracy of Cincinnati scale in prediction of stroke probability in patients referred to the emergency department of Poursina Hospital, Rasht, Iran, 2013 with neurologic symptoms. Three criteria of Cincinnati scale including facial droop, dysarthria, and upper extremity weakness as well as the final diagnosis of patients were gathered. Sensitivity, specificity, predictive values, and likelihood ratios of Cincinnati scale were calculated using SPSS version 20. Results: 448 patients were assessed. The agreement rate of Cincinnati scale and final diagnosis was 0.483 ± 0.055 (p<0.0001). The sensitivity of 93.19% (95% Cl: 90.11-95.54), specificity of 51.85% (95% Cl: 40.47-63.10), positive predictive value of 89.76% (95% Cl: 86.27-92.62), negative predictive value of 62.69% (95% Cl: 55.52-72.45), positive likelihood ratio of 1.94% (95% Cl: 1.54-2.43), and negative likelihood ratio of 0.13% (95% Cl: 0.09-0.20) were calculated. Conclusion: It seems that pre-hospital Cincinnati scale can be an appropriate screening tool in prediction of stroke in patients with acute neurologic syndromes

The removal of ρ-chlorophenol in aqueous cultures with free and alginate-immobilized cells of the microalga Tetraselmis suecica

The present study aimed at evaluating the ability of some isolated cyanobacterial and microalgal strains for the removal of ρ-chlorophenol (ρ-CP), an environmentally harmful contaminant. To identify the most efficient species, a screening program was carried out using 15 microalgal and cyanobacterial strains. Among them, Tetraselmis suecica was able to remove 67 % of the ρ-chlorophenol at an initial concentration of 20 mg L−1 from the medium within a 10-day period. The efficacy of the process was dependent on the ρ-chlorophenol concentration. At concentrations above 60 mg L−1 of the pollutant, no removal was observed due to the inhibitory effect of ρ-chlorophenol on the T. suecica cells. The effect of cell immobilization in alginate beads on T. suecica removal capacity was also examined. Using this technique, the removal efficacy for the initial ρ-CP concentration of 20 mg L−1 increased up to 94 %

HIF1 alpha isoforms in benign and malignant prostate tissue and their correlation to neuroendocrine differentiation

Background: Neuroendocrine (NE) differentiation in prostate cancer has been correlated with a poor prognosis and hormone refractory disease. In a previous report, we demonstrated the presence of immunoreactive cytoplasmic hypoxia inducible factor 1 alpha (HIF1 alpha), in both benign and malignant NE prostate cells. HIF1 alpha and HIF1 beta are two subunits of HIF1, a transcription factor important for angiogenesis. The aim of this study was to elucidate whether the cytoplasmic stabilization of HIF1 alpha in androgen independent NE differentiated prostate cancer is due to the presence of certain HIF1 alpha isoforms.Methods: We studied the HIF1 alpha isoforms present in 8 cases of benign prostate hyperplasia (BPH) and 43 cases of prostate cancer with and without NE differentiation using RT-PCR, sequencing analysis, immunohistochemistry and in situ hybridization.Results: We identified multiple isoforms in both benign and malignant prostate tissues. One of these isoforms, HIF1 alpha 1.2, which was previously reported to be testis specific, was found in 86% of NE-differentiated prostate tumors, 92% of HIF1 alpha immunoreactive prostate tumors and 100% of cases of benign prostate hyperplasia. Immunohistochemistry and in situ hybridization results showed that this isoform corresponds to the cytoplasmic HIF1 alpha present in androgen-independent NE cells of benign and malignant prostate tissue and co-localizes with immunoreactive cytoplasmic HIF1 beta.Conclusion: Our results indicate that the cytoplasmic stabilization of HIF1 alpha in NE-differentiated cells in benign and malignant prostate tissue is due to presence of an HIF1 alpha isoform, HIF1 alpha 1.2. Co-localization of this isoform with HIF1 beta indicates that the HIF1 alpha 1.2 isoform might sequester HIF1 beta in the cytoplasm

Prostate cancer and neuroendocrine differentiation. Molecular aspects in prostate cancer development

Hormone refractory prostate cancer occurs when androgen-deprivation therapy (ADT) fails to stop the growth of prostate cancer for any longer. Recent studies point towards a role for neuroendocrine (NE) differentiation in the development of hormone refractory disease. It has been hypothesized that NE-differentiated malignant tumor cells survive during ADT and promote development of androgen-independent disease through autocrine and paracrine signaling pathways. In vitro studies have shown that androgen depletion, stimulation with growth factors such as IL-6 and cAMP inducing agents cause NE-differentiation in prostate cancer cell lines. In this thesis, we have analyzed the tumorogenic characteristics of NE tumor cells with regard to expression of key transcription factors, stem cell markers and clinical prognostic markers. Hypoxia has been shown to induce increased tumor growth by promoting angiogenic and glycolytic pathways. Tumors overexpressing hypoxia inducible factors (HIF1a and HIF2a), important transcriptional activators of oxygen-regulated genes, are resistant to chemo- and radiotherapy. We found overexpression and cytoplasmic stabilization of HIF1a and HIF2a in androgen receptor negative NE cells in benign and malignant prostate tissue. Furthermore, we showed that stabilization of HIF1a in NE cells in prostate cancer is due to the presence of a HIF1a isoform, HIF1a1.2. This isoform is co-localized with ARNT, a subunit important for the function of HIF1 transcription factor. This finding indicates that the HIF1a1.2 isoform might sequester ARNT in the cytoplasm. We also studied presence of stem cell marker Oct 3/4 in prostate cancer and benign prostate hyperplasia. Transcription of type 1 of Oct 3/4 as well as protein expression with nuclear localization of Oct 3/4 were not detected in any of prostate tumors or benign prostate hyperplasia but we found only the cytoplasmic isoform 2 of Oct3/4 in prostate tumors with NE-differentiation and also in benign prostate hyperplasia. We studied NE-differentiation in hormone-naive high-grade prostate adenocarcinoma with four immunohistochemial NE markers, Chromogranin A (CgA), synaptophysin, serotonin and neuron-specific enolase (NSE). We showed that synaptophysin immunoreactivity detects the highest number of NE-differentiated tumors. In addition, NE-differentiation measured with synaptophysin, serotonin and NSE immunoreactivity, was correlated to Gleason grade 4 rather than Gleason grade 5 cancer. Univariate statistical analysis revealed that the immunoexpression of CgA, serotonin and NSE is correlated to longer patient survival time. In conclusion, NE-differentiation in hormone-naive high-grade prostate adenocarcinoma, measured with three of four NE markers, is correlated to Gleason grade 4 cancer, a better prognosis and longer patient survival time

Characterization of an alternative transcript of the human CREB3L2 gene.

CREB3L2, a member of the CREB3 family of transcription factors, spans >120 kbp and is composed of 12 exons. We characterized a widely expressed transcript of CREB3L2 generated by an intronic polyadenylation site in intron 4 of the gene. It could be translated to a CREB3L2 variant which is localized both in the nucleus and the endoplasmatic reticulum. The protein retains the N-terminal transactivation domain but lacks the DNA-binding domain, the transmembrane domain and the C-terminal part. Experiments using a GAL4 DNA-binding domain fusion model showed that the transcript is a transactivator but it cannot exert its function through the CRE and ATF6 binding sites and has little effect on the GRP78 promoter. Whether this transcript has a cellular function or is targeted for degradation by nonsense-mediated RNA decay system of RNA surveillance is currently unknown

Localization of immunoreactive HIF-1alpha and HIF-2alpha in neuroendocrine cells of both benign and malignant prostate glands.

BACKGROUND. Hypoxia induces increased tumor growth by promoting angiogenic and glycolytic pathways. Tumors expressing hypoxia-inducible factor-la (HIF-1 alpha), an important transcriptional activator of oxygen-regulated genes, are resistant to chemotherapy and radiotherapy. The major challenge in prostate cancer therapy today is to gain a better understanding of the development of hormone-refractory tumors, which is often characterized by neuroendocrine differentiation. Here we studied the expression of HIF-1 alpha and HIF-2 alpha in neuroendocrine cells of the benign prostate and in prostate cancer. METHODS. Tissue sections from 30 patients who underwent radical prostatectomy and from 21 patients operated by transurethral resection of the prostate were selected for immunohistochemical analysis for expression of HIF-l a, HIF-2a, androgen receptor (AR), neuroendocrine markers (chromogranin A, synaptophysin), and two gene products downstream of HIF-1a: VEGF and GAPDH. RESULTS. Immunoreactive HIF-1 alpha was detected in a subpopulation of AR-negative neuroendocrine cells in benign and malignant prostate tissue. Analysis of serial sections showed that the levels of expression of GAPDH and VEGF proteins are increased in AR-negative malignant neuroendocrine cells expressing HIF-1 alpha. in situ-hybridization indicated that HIF-1 alpha mRNA levels are not higher in neuroendocrine prostate cancer cells relative to corresponding non-neuroendocrine tumor cells. We also demonstrated induced stabilization of nuclear HIF-1 alpha in LNCaP cells by hypoxia and long-term stimulation with interleukin-6. Focal HIF-2 expression was detected in benign neuroendocrine-like cells and in malignant prostatic cells. CONCLUSIONS. The expression of HIF-1 alpha and HIF-2a in prostate cancer has been confirmed, but we also identified immunoreactive HIF-1 alpha and downstream gene products in benign and malignant prostate neuroendocrine cells. Prostate 67:1219-1229, 2007, (c) 2007 Wiley-Liss, Inc

Immunohistochemical Evaluation of Cell Cycle Regulators : Impact on Predicting Prognosis in Stage T1 Urinary Bladder Cancer

Background and Objective. The cell cycle is regulated by proteins at different checkpoints, and dysregulation of this cycle plays a role in carcinogenesis. Matrix metalloproteinases (MMPs) are enzymes that degrade collagen and promote tumour infiltration. The aim of this study was to evaluate the expression of various cell cycle regulators and MMPs, and to correlate such expression with progression and recurrence in patients with stage T1 urothelial carcinoma of the bladder (UCB). Patients and Methods. This population-based cohort study comprised 201 well-characterized patients with primary stage T1 urothelial carcinoma of the bladder. Immunohistochemistry was performed on formalin-fixed material to quantify expression of cell cycle regulators and two MMPs. Results. Normal expression of p53 and abnormal expression of MMP9 were associated with greater risk of tumour recurrence. Also, normal p16 expression was related to a lower risk of tumour progression. MMP2, p21, cyclin D1, and pRb showed no significant results that could estimate progression or recurrence. Conclusions. Normal p16 expression is associated with a lower risk of tumour progression, but immunohistochemistry on cell cycle regulators and MMPs has little value in predicting the prognosis in stage T1 UCB.On the day of the defence day the status of this article was:Manuscript</p

Immunohistochemical Evaluation of Cell Cycle Regulators : Impact on Predicting Prognosis in Stage T1 Urinary Bladder Cancer

Background and Objective. The cell cycle is regulated by proteins at different checkpoints, and dysregulation of this cycle plays a role in carcinogenesis. Matrix metalloproteinases (MMPs) are enzymes that degrade collagen and promote tumour infiltration. The aim of this study was to evaluate the expression of various cell cycle regulators and MMPs, and to correlate such expression with progression and recurrence in patients with stage T1 urothelial carcinoma of the bladder (UCB). Patients and Methods. This population-based cohort study comprised 201 well-characterized patients with primary stage T1 urothelial carcinoma of the bladder. Immunohistochemistry was performed on formalin-fixed material to quantify expression of cell cycle regulators and two MMPs. Results. Normal expression of p53 and abnormal expression of MMP9 were associated with greater risk of tumour recurrence. Also, normal p16 expression was related to a lower risk of tumour progression. MMP2, p21, cyclin D1, and pRb showed no significant results that could estimate progression or recurrence. Conclusions. Normal p16 expression is associated with a lower risk of tumour progression, but immunohistochemistry on cell cycle regulators and MMPs has little value in predicting the prognosis in stage T1 UCB.On the day of the defence day the status of this article was:Manuscript</p