Detection of adeno-associated virus type 2 genome in cervical carcinoma

Adeno-associated virus (AAV) can impair the replication of other viruses. Adeno-associated virus seroprevalences have been reported to be lower among women with cervical cancer. In-vitro, AAV can interfere with the production of human papillomavirus virions. Adeno-associated virus-2 DNA has also been detected in cervical cancer tissue, although not consistently. To evaluate the role of AAV infection in relation to invasive cervical cancer, we performed a nested case–control study within a retrospectively followed population-based cohort. A total of 104 women who developed invasive cervical cancer on average 5.6 years of follow-up (range: 0.5 months–26.2 years) and 104 matched control-women who did not develop cervical cancer during the same follow-up time were tested for AAV and human papillomavirus by polymerase chain reaction. At baseline, two (2%) case-women and three (3%) control-women were positive for AAV-2 DNA. At the time of cancer diagnosis, 12 (12%) case-women and 3 (3%) matched control-women were positive for AAV-2 DNA. Persisting AAV infection was not evident. In conclusion, AAV-2 DNA was present in a low proportion of cervical cancers and we found no evidence that the presence of AAV in cervical smears of healthy women would be associated with reduced risk of cervical cancer

AAV-mediated human PEDF inhibits tumor growth and metastasis in murine colorectal peritoneal carcinomatosis model

<p>Abstract</p> <p>Background</p> <p>Angiogenesis plays an important role in tumor growth and metastasis, therefore antiangiogenic therapy was widely investigated as a promising approach for cancer therapy. Recently, pigment epithelium-derived factor (PEDF) has been shown to be the most potent inhibitor of angiogenesis. Adeno-associated virus (AAV) vectors have been intensively studied due to their wide tropisms, nonpathogenicity, and long-term transgene expression <it>in vivo</it>. The objective of this work was to evaluate the ability of AAV-mediated human PEDF (hPEDF) as a potent tumor suppressor and a potential candidate for cancer gene therapy.</p> <p>Methods</p> <p>Recombinant AAV₂encoding hPEDF (rAAV₂-hPEDF) was constructed and produced, and then was assigned for <it>in vitro </it>and <it>in vivo </it>experiments. Conditioned medium from cells infected with rAAV₂-hPEDF was used for cell proliferation and tube formation tests of human umbilical vein endothelial cells (HUVECs). Subsequently, colorectal peritoneal carcinomatosis (CRPC) mouse model was established and treated with rAAV₂-hPEDF. Therapeutic efficacy of rAAV₂-hPEDF were investigated, including tumor growth and metastasis, survival time, microvessel density (MVD) and apoptosis index of tumor tissues, and hPEDF levels in serum and ascites.</p> <p>Results</p> <p>rAAV₂-hPEDF was successfully constructed, and transmission electron microscope (TEM) showed that rAAV₂-hPEDF particles were non-enveloped icosahedral shape with a diameter of approximately 20 nm. rAAV₂-hPEDF-infected cells expressed hPEDF protein, and the conditioned medium from infected cells inhibited proliferation and tube-formation of HUVECs <it>in vitro</it>. Furthermore, in CRPC mouse model, rAAV₂-hPEDF significantly suppressed tumor growth and metastasis, and prolonged survival time of treated mice. Immunofluorescence studies indicated that rAAV₂-hPEDF could inhibit angiogenesis and induce apoptosis in tumor tissues. Besides, hPEDF levels in serum and ascites of rAAV₂-hPEDF-treated mice were significant higher than those in rAAV₂-null or normal saline (NS) groups.</p> <p>Conclusions</p> <p>Thus, our results suggest that rAAV₂-hPEDF may be a potential candidate as an antiangiogenic therapy agent.</p

Epstein-Barr Virus Stimulates Torque Teno Virus Replication: A Possible Relationship to Multiple Sclerosis

Viral infections have been implicated in the pathogenesis of multiple sclerosis. Epstein-Barr virus (EBV) has frequently been investigated as a possible candidate and torque teno virus (TTV) has also been discussed in this context. Nevertheless, mechanistic aspects remain unresolved. We report viral replication, as measured by genome amplification, as well as quantitative PCR of two TTV-HD14 isolates isolated from multiple sclerosis brain in a series of EBV-positive and -negative lymphoblastoid and Burkitt's lymphoma cell lines. Our results demonstrate the replication of both transfected TTV genomes up to day 21 post transfection in all the evaluated cell lines. Quantitative amplification indicates statistically significant enhanced TTV replication in the EBV-positive cell lines, including the EBV-converted BJAB line, in comparison to the EBV-negative Burkitt's lymphoma cell line BJAB. This suggests a helper effect of EBV infections in the replication of TTV. The present study provides information on a possible interaction of EBV and TTV in the etiology and progression of multiple sclerosis

Measurement of inclusive π0\pi^{0} production in hadronic Z0Z^{0} decays

An analysis is presented of inclusive \pi^0 production in Z^0 decays measured with the DELPHI detector. At low energies, \pi^0 decays are reconstructed by \linebreak using pairs of converted photons and combinations of converted photons and photons reconstructed in the barrel electromagnetic calorimeter (HPC). At high energies (up to x_p = 2 \cdot p_{\pi}/\sqrt{s} = 0.75) the excellent granularity of the HPC is exploited to search for two-photon substructures in single showers. The inclusive differential cross section is measured as a function of energy for {q\overline q} and {b \bar b} events. The number of \pi^0's per hadronic Z^0 event is N(\pi^0)/ Z_{had}^0 = 9.2 \pm 0.2 \mbox{(stat)} \pm 1.0 \mbox{(syst)} and for {b \bar b}~events the number of \pi^0's is {\mathrm N(\pi^0)/ b \overline b} = 10.1 \pm 0.4 \mbox{(stat)} \pm 1.1 \mbox{(syst)} . The ratio of the number of \pi^0's in b \overline b events to hadronic Z^0 events is less affected by the systematic errors and is found to be 1.09 \pm 0.05 \pm 0.01. The measured \pi^0 cross sections are compared with the predictions of different parton shower models. For hadronic events, the peak position in the \mathrm \xi_p = \ln(1/x_p) distribution is \xi_p^{\star} = 3.90^{+0.24}_{-0.14}. The average number of \pi^0's from the decay of primary \mathrm B hadrons is found to be {\mathrm N} (B \rightarrow \pi^0 \, X)/\mbox{B hadron} = 2.78 \pm 0.15 \mbox{(stat)} \pm 0.60 \mbox{(syst)}

Search for new phenomena using single photon events in the DELPHI detector at LEP

Data are presented on the reaction \epem~\into~\gamma + no other detected particle at center-of-mass energies, \sqs = 89.48 GeV, 91.26 GeV and 93.08 GeV. The cross section for this reaction is related directly to the number of light neutrino generations which couple to the \zz boson, and to several other phenomena such as excited neutrinos, the production of an invisible `X' particle, a possible magnetic moment of the tau neutrino, and neutral monojets. Based on the observed number of single photon events, the number of light neutrinos which couple to the \zz is measured to be N_\nu = 3.15 \pm 0.34. No evidence is found for anomalous production of energetic single photons, and upper limits at the 95\% confidence level are determined for excited neutrino production (BR < 4-9 \times 10^{-6}), production of an invisible `X' particle (\sigma < 0.1 pb), and the magnetic moment of the tau neutrino (< 5.2 \times 10^{-6} \mu_B). No event with the topology of a neutral monojet is found, and this corresponds to the limit \sigma < 0.044/\epsilon pb at the 95\% confidence level, where \epsilon is the unknown overall monojet detection efficiency

Measurement of the Bd0^{0}_{d} oscillation frequency using kaons, leptons and jet charge

A measurement of the mass difference, \Delta m_d, between the two physical \mbox{B}^0_d states has been obtained from the analysis of the impact parameter distribution of a lepton emitted at large transverse momentum (p_t) relative to the jet axis and from the analysis of the flight distance distribution of secondary vertices tagged by either a high p_t lepton or an identified kaon. In the opposite hemisphere of the event, the charge of the initial quark has been evaluated using a high p_t lepton, a charged kaon or the mean jet charge. With 1.7 million hadronic Z^0 decays recorded by DELPHI between 1991 and 1993, \Delta m_d is found to be: \Delta m_d = 0.531^{+0.050}_{-0.046} ~(stat.) \pm 0.078 ~(syst.) ~ {\mathrm{ps}}^{-1} \,

Energy dependence of the differences between the quark and gluon jet fragmentation

Three jet events arising from decays of the Z boson, collected by the DELPHI detector, were used to measure differences in quark and gluon fragmentation. Gluon jets were anti-tagged by identifying b quark jets. Unbiased quark jets came from events with two jets plus one photon. Quark and gluon jet properties in different energy ranges were compared for the first time within the same detector. Quark and gluon jets of nearly the same energy in symmetric three jet event topologies were also compared. Using three independent methods, the average value of the ratio of the mean charged multiplicities of gluon and quark jets is $$=1.241\pm 0.015\ (stat.) \pm 0.025\ (syst.).$$ Gluon jets are broader and produce fragments with a softer energy spectrum than quark jets of equivalent energy. The string effect has been observed in fully symmetric three jet events. The measured ratio R_{\gamma} of the charged particle flow in the q\overline{q} inter-jet region of the q\bar{q}g and q\bar{q}\gamma samples agrees with the perturbative QCD expectation. The dependence of the mean charged multiplicity on the hadronic center-of-mass energy was analysed in photon plus n-jet events. The value for \alpha_s(M_Z) determined from these data using a QCD prediction with corrections at leading and next-to-leading order is \[ \alpha_s(M_Z)=0.116 \pm 0.003\ (stat.) \pm 0.009\ (syst.). \

Search for Neutral Heavy Leptons Produced in Z Decays

Weak isosinglet Neutral Heavy Leptons ($\nu_m$) have been searched for using data collected by the DELPHI detector corresponding to $3.3\times 10^{6}$ hadronic~Z$^{0}$ decays at LEP1. Four separate searches have been performed, for short-lived $\nu_m$ production giving monojet or acollinear jet topologies, and for long-lived $\nu_m$ giving detectable secondary vertices or calorimeter clusters. No indication of the existence of these particles has been found, leading to an upper limit for the branching ratio $BR($Z$^0\rightarrow \nu_m \overline{\nu})$ of about $1.3\times10^{-6}$ at 95\% confidence level for $\nu_m$ masses between 3.5 and 50 GeV/$c^2$. Outside this range the limit weakens rapidly with the $\nu_m$ mass. %Special emphasis has been given to the search for monojet--like topologies. One event %has passed the selection, in agreement with the expectation from the reaction: %$e^+e^- \rightarrow\ell \bar\ell \nu\bar\nu$. The results are also interpreted in terms of limits for the single production of excited neutrinos

Search for Lepton Flavour Number violating Z0Z^0-Decays

A search for lepton flavour number violating $Z^0$ decays in the channels \begin{center} $Z^0\rightarrow \mu\tau$,\\ $Z^0\rightarrow e\tau$, \\ $Z^0\rightarrow e\mu$, \\ \end{center} using the DELPHI detector with data collected during the 1991--94 LEP runs, is described. No signal was found. Upper limits at 95\% confidence level for the respective branching fractions of $1.2\times 10^{-5}$, $2.2\times 10^{-5}$, and $0.25\times 10^{-5}$, were obtained