Enhancement of experimental metastasis by tumor necrosis factor

The influence of endogenous and exogenous tumor necrosis factor (TNF) on metastasis was investigated in an experimental fibrosarcoma metastasis model. A single intraperitoneal injection of recombinant human (rh) TNF or recombinant mouse (rm) TNF into mice 5 h before intravenous inoculation of methylcholanthrene-induced fibrosarcoma cells (CFS1) induced a significant enhancement of the number of metastases in the lung. Dose responses of rmTNF and rhTNF demonstrated a stronger metastasis-augmenting effect by rmTNF compared with rhTNF. This effect was time dependent, as administration of rmTNF 5 h before or 1 h but not 24 h after tumor cell inoculation caused an increase of tumor cell colony formation on the lung surface, suggesting an influence of TNF on the vascular adhesion and diapedesis of tumor cells. Since tumor-bearing mice showed an enhanced ability to produce TNF after endotoxin injection compared to control mice, tumor-bearing mice were treated with anti-mTNF antibodies. Neutralization of endogenous tumor-induced TNF led to a significant decrease of the number of pulmonary metastases. Histological analysis of micrometastases in the lung on day 5 by silver staining of proteins associated with nucleolar organizer regions revealed more metastatic foci and augmented proliferative activity of the tumor cells after rmTNF pretreatment of mice. However, no direct effect of rmTNF on the proliferation rate of tumor cells was seen in vitro. These findings suggest that low doses of endogenous TNF or administered TNF during cytokine therapy might enhance the metastatic potential of circulating tumor cells

Analysis of a c0t-1 library enables the targeted identification of minisatellite and satellite families in Beta vulgaris

Zakrzewski F, Wenke T, Holtgräwe D, Weisshaar B, Schmidt T. Analysis of a c0t-1 library enables the targeted identification of minisatellite and satellite families in Beta vulgaris. BMC Plant Biology. 2010;10(1): 8.BACKGROUND: Repetitive DNA is a major fraction of eukaryotic genomes and occurs particularly often in plants. Currently, the sequencing of the sugar beet (Beta vulgaris) genome is under way and knowledge of repetitive DNA sequences is critical for the genome annotation. We generated a c0t-1 library, representing highly to moderately repetitive sequences, for the characterization of the major B. vulgaris repeat families. While highly abundant satellites are well-described, minisatellites are only poorly investigated in plants. Therefore, we focused on the identification and characterization of these tandemly repeated sequences. RESULTS: Analysis of 1763 c0t-1 DNA fragments, providing 442 kb sequence data, shows that the satellites pBV and pEV are the most abundant repeat families in the B. vulgaris genome while other previously described repeats show lower copy numbers. We isolated 517 novel repetitive sequences and used this fraction for the identification of minisatellite and novel satellite families. Bioinformatic analysis and Southern hybridization revealed that minisatellites are moderately to highly amplified in B. vulgaris. FISH showed a dispersed localization along most chromosomes clustering in arrays of variable size and number with exclusion and depletion in distinct regions. CONCLUSION: The c0t-1 library represents major repeat families of the B. vulgaris genome, and analysis of the c0t-1 DNA was proven to be an efficient method for identification of minisatellites. We established, so far, the broadest analysis of minisatellites in plants and observed their chromosomal localization providing a background for the annotation of the sugar beet genome and for the understanding of the evolution of minisatellites in plant genomes

High survivin expression as a risk factor in patients with anal carcinoma treated with concurrent chemoradiotherapy

Purpose: To investigate the prognostic value of survivin expression in pretreatment specimens from patients with anal cancer treated with concurrent 5-FU and mitomycin C-based chemoradiation (CRT). Material and methods: Immunohistochemical staining for survivin was performed in pretreatment biopsies of 62 patients with anal carcinoma. Survivin expression was correlated with clinical and histopathological characteristics as well as local failure free- (LFFS), distant metastases free- (DMFS), cancer specific- (CSS), and overall survival (OS). Results: Survivin staining intensity was weak in 10%, intermediate in 48% and intense in 42% of the patients. No association between survivin expression and clinicopathologic factors (tumor stage, age and HIV status) could be shown. In univariate analysis, the level of survivin staining was significantly correlated with DMFS (low survivin vs. high survivin: 94% vs. 74%, p=0.04). T-stage, N-stage and the tumor grading were significantly associated with OS and CSS and with DMFS and LFFS, respectively. In multivariate analysis, survivin was confirmed as independent prognostic parameter for DMFS (RR, 0.04; p=0.02) and for OS (RR, 0.27; p=0.04). Conclusion: Our results demonstrated that the level of pretreatment survivin is correlated with the clinical outcome in patients with anal carcinoma treated with concurrent CRT. Further studies are warranted to elucidate the complex role of survivin for the oncologic treatment and to exploit the protein as a therapeutic target in combined modality treatment of anal cancer

On the monodromy action on Milnor fibers of graphic arrangements

We analyze the monodromy action, over the rationals, on the first homology group of the Milnor fiber, for arbitrary subarrangements of Coxeter arrangements. We propose a combinatorial formula for the monodromy action, involving Aomoto complexes in positive characteristic. We verify the formula, in cases A, B and D.Comment: 23 pages; updated reference

Differential RelA- and RelB-dependent gene transcription in LTβR-stimulated mouse embryonic fibroblasts

<p>Abstract</p> <p>Background</p> <p>Lymphotoxin signaling via the lymphotoxin-β receptor (LTβR) has been implicated in biological processes ranging from development of secondary lymphoid organs, maintenance of spleen architecture, host defense against pathogens, autoimmunity, and lipid homeostasis. The major transcription factor that is activated by LTβR crosslinking is NF-κB. Two signaling pathways have been described, the classical inhibitor of NF-κB α (IκBα)-regulated and the alternative p100-regulated pathway that result in the activation of p50-RelA and p52-RelB NF-κB heterodimers, respectively.</p> <p>Results</p> <p>Using microarray analysis, we investigated the transcriptional response downstream of the LTβR in mouse embryonic fibroblasts (MEFs) and its regulation by the RelA and RelB subunits of NF-κB. We describe novel LTβR-responsive genes that were regulated by RelA and/or RelB. The majority of LTβR-regulated genes required the presence of both RelA and RelB, revealing significant crosstalk between the two NF-κB activation pathways. Gene Ontology (GO) analysis confirmed that LTβR-NF-κB target genes are predominantly involved in the regulation of immune responses. However, other biological processes, such as apoptosis/cell death, cell cycle, angiogenesis, and taxis were also regulated by LTβR signaling. Moreover, LTβR activation inhibited expression of a key adipogenic transcription factor, peroxisome proliferator activated receptor-γ (<it>pparg</it>), suggesting that LTβR signaling may interfere with adipogenic differentiation.</p> <p>Conclusion</p> <p>Microarray analysis of LTβR-stimulated fibroblasts provided comprehensive insight into the transcriptional response of LTβR signaling and its regulation by the NF-κB family members RelA and RelB.</p

Phone vs. Tangible in museums: A comparative study

Despite years of HCI research on digital technology in museums, it is still unclear how different interactions impact on visitors’. A comparative evaluation of smart replicas, phone app and smart cards looked at the personal preferences, behavioural change, and the appeal of mobiles in museums. 76 participants used all three interaction modes and gave their opinions in a questionnaire; participants interaction was also observed. The results show the phone is the most disliked interaction mode while tangible interaction (smart card and replica combined) is the most liked. Preference for the phone favour mobility to the detriment of engagement with the exhibition. Different behaviours when interacting with the phone or the tangibles where observed. The personal visiting style appeared to be only marginally affected by the device. Visitors also expect museums to provide the phones against the current trend of developing apps in a “bring your own device” approach

Implication of bisphosphonate use in the treatment of SAPHO syndrome: Case report and discussion of current literature

AbstractEven though increasing knowledge is emerging about synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome its pathogenesis remains enigmatic. Women are preferentially affected by SAPHO syndrome. Here we present the case of a 39-year-old woman suffering from this syndrome whose bone involvement was first interpreted as diffuse sclerosing osteomyelitis of the mandible. As treatment with clindamycin did not improve the symptoms, the decision was made to administer bisphosphonates intravenously. This treatment led to a rapid improvement in symptoms, which could be explained by the apparent tendency of bisphosphonates to exert a positive effect on the jaw. With this case report we attempt to offer an explanation for the influence of this group of medications on patients suffering from SAPHO syndrome with mandibular involvement

Mapping of subthalamic nucleus using microelectrode recordings during deep brain stimulation

Alongside stereotactic magnetic resonance imaging, microelectrode recording (MER) is frequently used during the deep brain stimulation (DBS) surgery for optimal target localization. The aim of this study is to optimize subthalamic nucleus (STN) mapping using MER analytical patterns. 16 patients underwent bilateral STN-DBS. MER was performed simultaneously for 5 microelectrodes in a setting of Ben's-gun pattern in awake patients. Using spikes and background activity several different parameters and their spectral estimates in various frequency bands including low frequency (2-7 Hz), Alpha (8-12 Hz), Beta (sub-divided as Low_Beta (13-20 Hz) and High_Beta (21-30 Hz)) and Gamma (31 to 49 Hz) were computed. The optimal STN lead placement with the most optimal clinical effect/ side-effect ratio accorded to the maximum spike rate in 85% of the implantation. Mean amplitude of background activity in the low beta frequency range was corresponding to right depth in 85% and right location in 94% of the implantation respectively. MER can be used for STN mapping and intraoperative decisions for the implantation of DBS electrode leads with a high accuracy. Spiking and background activity in the beta range are the most promising independent parameters for the delimitation of the proper anatomical site

Riscurile și beneficiile înregistrării cu microelectrod în chirurgia bolii Parkinson

Background. Microelectrode recording is believed to improve the outcome by enhancing the precision of electrodes used in deep brain stimulation in patients with Parkinson’s Disease. There is a trend that higher number of penetrations correlate with high rate of hemorrhagic complications. Objective of the study. Determine the clinical outcome of patients stimulated decentrally compared to those placed centrally. Additionally, to assess whether a higher number of penetrations correlate with higher rates of intracranial bleeding. Material and Methods. This monocentric study included 556 patients with bilateral STN-DBS and relies on a large prospectively established database. Data were available from 400 patients. The outcome parameter was the stimulation-induced improvement of the UPDRS for PD. We compared patients with both electrodes centrally to that bi-decentrally. Also, we determined the rate of surgical complications. Results. A decentral tract was chosen in 41% of the electrodes based on clinical grounds (central, n = 471 electrodes; decentral, n = 329). Motor symptom improvement was not different between patients with electrodes implanted bilaterally in the central (44.39% ± 22.71) or decentral (43,22% ± 17) trajectory bilaterally (p = 0.5571). Similar results were obtained for the hemibody score and subscores for akinesia, tremor, rigidity, postural instability and gait disorder. The overall bleeding rate was 2,78% and not depending on the number of penetrations. Conclusion. Outcomes between the groups with central or decentral electrode trajectories did not differ and, therefore, the use of mMER is likely to improve outcome quality. Comparison with other cohorts does not disclose a higher rate of bleeding complications in this cohort with mMER. Introducere. În chirurgia bolii Parkinson, înregistrarea cu microelectrod se utilizează pentru determinarea punctului optim pentru stimulare cerebrală profundă. Se consideră că numărul crescut de penetrații corelează cu rata mai mare a complicațiilor hemoragice postoperatorii. Scopul lucrării. De a determina efectul clinic al pacienților stimulați cu electrozi bicentral versus cei implantați decentral bilateral. De asemenea, de a evalua dacă numărul mai mare de penetrații corelează cu rata mai mare a sângerării intracraniene. Material și Metode. Acest studiu monocentric a inclus 556 de pacienți cu boala Parkinson, stimulați bilateral, bază pe o bază de date prospectivă. Datele complete au fost găsite la 400 de pacienți. Parametrul pentru comparație a fost scala UPDRS pentru BP. Studiul nostru a comparat pacienții cu ambii electrozi implantați bilateral central și decentral. De asemenea, s-a studiat rata sângerării postoperatorii. Rezultate. Traiectorie decentrală s-a ales în 41% din electrozi pe baza la rezultatul clinic (central - 471 electrozi, decentral - 329). Ameliorarea simptomelor motorii nu diferă între grupurile de pacienți cu electrozi implantați bilateral central (44.39% ± 22.71) sau decentral (43, 22% ± 17), p = 0.56. Aceleași rezultate s-au obținut pentru scorul hemibody și subscoruri ca: akinezia, tremorul, rigiditatea, tulburările de statică și mers. Incidența hemoragiei a fost de 2.78% și nu corelează cu numărul de penetrații cu microelectroade. Concluzii. Rezultatul clinic al pacienților cu ambii electrozi bilateral central și decentral nu diferă. Astfel, utilizarea MER poate ameliora rezultatul final. Totodată, incidența complicațiilor postoperatorii hemoragice în studiul nostru nu este mai mare decât în alte studii