Biomedical subjects

L M Mir

Publications and source records attributed to L M Mir.

At least 109 records · Page 6Linked to original sources

PubMed2003

Measurements of the branching fractions and bounds on the charge asymmetries of charmless three-body charged B decays.

We present measurements of branching fractions and charge asymmetries for charmless B-meson decays to three-body final states of charged pions and kaons. The analysis uses 81.8 fb(-1) of data collected at the Upsilon(4S) resonance with the BABAR detector at the SLAC PEP-II asymmetric B Factory. We measure the branching fractions B(B+-->pi(+)pi(-)pi(+))=(10.9+/-3.3+/-1.6)x10(-6), B(B+-->K+pi(-)pi(+))=(59.1+/-3.8+/-3.2)x10(-6), and B(B+-->K+K-K+)=(29.6+/-2.1+/-1.6)x10(-6) and provide 90% C.L. upper limits for other decays. We observe no charge asymmetries for these modes.

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PubMed2003

Observation of the decay B+/--->pi+/-pi0, study of B+/--->K+/-pi0, and search for B0-->pi0pi0.

We present results for the branching fractions and charge asymmetries in B+/--->h(+/-)pi(0) (where h(+/-)=pi(+/-),K+/-) and a search for the decay B0-->pi(0)pi(0) using a sample of approximately 88 x 10(6) BBmacr; pairs collected by the BABAR detector at the PEP-II asymmetric-energy B Factory at SLAC. We measure B(B+/--->pi(+/-)pi(0))=(5.5(+1.0)(-0.9)+/-0.6)x10(-6), where the first error is statistical and the second is systematic. The B+/--->pi(+/-)pi(0) signal has a significance of 7.7sigma including systematic uncertainties. We simultaneously measure the K+/-pi(0) branching fraction to be B(B+/--->K+/-pi(0))=(12.8(+1.2)(-1.1)+/-1.0)x10(-6). The charge asymmetries are Api(+/-)(pi(0))=-0.03(+0.18)(-0.17)+/-0.02 and AK+/-(pi(0))=-0.09+/-0.09+/-0.01. We place a 90% confidence-level upper limit on the branching fraction B(B0-->pi(0)pi(0)) of 3.6 x 10(-6).

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PubMed2003

Observation of a narrow meson state decaying to D(+)(s)pi(0) at a mass of 2.32 GeV/c(2).

We have observed a narrow state near 2.32 GeV/c(2) in the inclusive D(+)(s)pi(0) invariant mass distribution from e(+)e(-) annihilation data at energies near 10.6 GeV. The observed width is consistent with the experimental resolution. The small intrinsic width and the quantum numbers of the final state indicate that the decay violates isospin conservation. The state has natural spin-parity and the low mass suggests a J(P)=0(+) assignment. The data sample corresponds to an integrated luminosity of 91 fb(-1) recorded by the BABAR detector at the SLAC PEP-II asymmetric-energy e(+)e(-) storage ring.

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PubMed2003

Evidence for B+-->J/psip(-)Lambda; and search for B0-->J/psip(-)p.

We have performed a search for the decays B+-->J/psip(-)Lambda; and search for B0-->J/psip(-)p. in a data set of (88.9+/-1.0) x 10(6) Upsilon(4S) decays collected by the BABAR experiment at the PEP-II e(+)e(-) storage ring at the Stanford Linear Accelerator Center. Four charged B candidates have been observed with an expected background of 0.21+/-0.14 events. The corresponding branching fraction is (12(+9)(-6)) x 10(-6), where statistical and systematic uncertainties have been combined. The result can be interpreted as a 90% confidence level (C.L.) upper limit of 26 x 10(-6). We also find one B0 candidate, with an expected background of 0.64+/-0.17 events, implying a 90% C.L. upper limit of 1.9 x 10(-6).

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PubMed2003

Measurement of the branching fraction, and bounds on the CP-violating asymmetries, of neutral B decays to D*+/- D-/+.

We present measurements of the branching fraction and CP-violating asymmetries for neutral B decays to D(*+/-)D-/+. The measurement uses a data sample of approximately 88x10(6) Upsilon(4S)-->BBmacr; decays collected with the BABAR detector at the SLAC PEP-II asymmetric-energy e(+)-e(-) collider. By fully reconstructing the D(*+/-)D-/+ decay products, we measure the branching fraction to be (8.8+/-1.0+/-1.3)x10(-4) and the time-integrated CP-violating asymmetry between the rates to D(*-)D+ and D(*+)D- to be A=-0.03+/-0.11+/-0.05. We also measure the time-dependent CP-violating asymmetry parameters to be S(-+)=-0.24+/-0.69+/-0.12, C(-+)=-0.22+/-0.37+/-0.10 for B-->D(*-)D+ and S(+-)=-0.82+/-0.75+/-0.14, C(+-)=-0.47+/-0.40+/-0.12 for B-->D(*+)D-. In each case, the first error is statistical and the second error is systematic.

Journal Article↗

PubMed2003

In vivo evolution of tumour cells after the generation of double-strand DNA breaks.

In vitro, the ratio of single- to double-strand DNA breaks (DSB) and their absolute values determine the cell death pathway. The consequences of the generation of various numbers of DSB generated in vivo in tumour cells have been analysed in two different experimental tumour models. Synchronisation of DSB generation and control of their number have been achieved using different doses of bleomycin (BLM) and tumour cell permeabilisation by means of locally delivered electric pulses. According to BLM dose, different cell death pathways are observed. At a low therapeutic dose, a mitotic cell death pathway is detected. It is characterised by the appearance of 'atypical mitosis', TUNEL and caspase-3 positive, 24 h after the treatment, and later by the presence of typical apoptotic figures, mainly TUNEL positive but caspase-3 negative. Caspase-3 is thus an early marker of apoptosis. Mitotic cell death is also followed by lymphocytic infiltration reaction. At high doses of BLM, pseudoapoptosis is detected within a few minutes after the treatment. These cell death pathways are discussed as a function of the number of DSB generated, by comparison with previous results obtained in vitro using BLM or ionising radiation.

Animals↗

PubMed2003

Study of the rare decays B0-->D(()+)(s)pi(-) and B0-->D(()-)(s)K+.

We report evidence for the decays B0-->D(+)(s)pi(-) and B0-->D(-)(s)K+ and the results of a search for B0-->D(*+)(s)pi(-) and B0-->D(*-)(s)K+ in a sample of 84 x 10(6) upsilon(4S) decays into BB pairs collected with the BABAR detector at the PEP-II asymmetric-energy e(+)e(-) storage ring. We measure the branching fractions B(B0-->D(+)(s)pi(-))=[3.2+/-0.9(stat)+/-1.0(syst)] x 10(-5) and B(B0-->D(-)(s)K+)=[3.2+/-1.0(stat)+/-1.0(syst)] x 10(-5). We also set 90% C.L. limits B(B0-->D(*+)(s)pi(-))<4.1 x 10(-5) and B(B0-->D(*-)(s)K+)<2.5 x 10(-5).

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PubMed2003

Measurement of the Cabibbo-Kobayashi-Maskawa matrix element V(ub) with B-->rhoenu decays.

We present a measurement of the branching fraction for the rare decays B-->rhoenu and extract a value for the magnitude of V(ub), one of the smallest elements of the Cabibbo-Kobayashi-Maskawa quark-mixing matrix. The results are given for five different calculations of form factors used to para-metrize the hadronic current in semileptonic decays. Using a sample of 55 x 10(6) BB meson pairs recorded with the BABAR detector at the PEP-II e(+)e(-) storage ring, we obtain B(B0-->rho(-)e(+)nu)=(3.29+/-0.42+/-0.47+/-0.55) x 10(-4) and |V(ub)|=(3.64+/-0.22+/-0.25(+0.39)(-0.56)) x 10(-3), where the uncertainties are statistical, systematic, and theoretical, respectively.

Journal Article↗

PubMed2003

Measurement of the B0-->J/psipi+pi- branching fraction.

We present a measurement of the branching fraction for the decay of the neutral B meson into the final state J/psipi(+)pi(-). The data set contains approximately 56 x 10(6) BB pairs produced at the Upsilon(4S) resonance and recorded with the BABAR detector at the PEP-II asymmetric-energy e(+)e(-) storage ring. The result of this analysis is B(B0-->J/psipi(+)pi(-))=(4.6+/-0.7+/-0.6) x 10(-5), where the first error is statistical and the second is systematic. In addition, we measure B(B0-->J/psirho(0))=(1.6+/-0.6+/-0.4) x 10(-5).

Journal Article↗

PubMed2003

Electrochemotherapy: a new treatment of solid tumors.

Electrochemotherapy is a new local treatment of the solid tumors that can be defined as the local potentiation, by means of permeabilizing electric pulses, of the antitumor activity of non-permeant (e.g. bleomycin) or low-permeant (e.g. cisplatin) anticancer drugs. The electric pulses are delivered locally on the solid tumors, after the intravenous or intralesional injection of the chemotherapy agent. In this review, the basis of the electrochemotherapy are recalled. Then, after summarizing clinical data, we present some results of the European project Cliniporator, as well as the new pulse generator, the Cliniporator, that incorporates new features resulting from this research project, and that is fully conceived for a clinical use. Finally, future perspectives are discussed.

Animals↗

PubMed2002

Measurements of branching fractions and CP-violating asymmetries in B0-->pi+pi-, K+pi-, K+K- decays.

We present measurements of branching fractions and CP-violating asymmetries for two-body neutral B meson decays to charged pions and kaons based on a sample of about 88x10(6) Upsilon(4S)-->BB decays. From a time-independent fit we measure the charge-averaged branching fractions B(B0-->pi+pi-)=(4.7+/-0.6+/-0.2)x10(-6), B(B0-->K+pi-)=(17.9+/-0.9+/-0.7)x10(-6), and the direct CP-violating charge asymmetry A(Kpi)=-0.102+/-0.050+/-0.016 [-0.188,-0.016], where the ranges in square brackets indicate the 90% confidence intervals. From a time-dependent fit we measure the B0-->pi+pi- CP-violating parameters S(pipi)=0.02+/-0.34+/-0.05 [-0.54,+0.58] and C(pipi)=-0.30+/-0.25+/-0.04 [-0.72,+0.12].

Journal Article↗

PubMed2002

Measurement of the CP asymmetry amplitude sin2beta with B0 mesons.

We present results on time-dependent CP asymmetries in neutral B decays to several CP eigenstates. The measurements use a data sample of about 88 x 10(6) Upsilon(4S)-->B(-)B decays collected between 1999 and 2002 with the BABAR detector at the PEP-II asymmetric-energy B factory at SLAC. We study events in which one neutral B meson is fully reconstructed in a final state containing a charmonium meson and the other B meson is determined to be either a B(0) or B(-0) from its decay products. The amplitude of the CP asymmetry, which in the standard model is proportional to sin2beta, is derived from the decay-time distributions in such events. We measure sin2beta=0.741+/-0.067(stat)+/-0.034(syst) and |lambda|=0.948+/-0.051(stat)+/-0.030(syst). The magnitude of lambda is consistent with unity, in agreement with the standard model expectation of no direct CP violation in these modes.

Journal Article↗

PubMed2002

Treatment of cancer with cryochemotherapy.

Cryosurgery employs freezing to destroy solid tumours. However, frozen cells can survive and cause cancer recurrence. Bleomycin, an anticancer drug with a huge intrinsic cytotoxicity is normally not very effective because it is nonpermeant. We report that freezing facilitates bleomycin penetration into cells making it toxic to cryosurgery surviving cells at concentrations that are non-toxic systemically.

Animals↗

PubMed2002

The effect of pulse repetition frequency on the uptake into electropermeabilized cells in vitro with possible applications in electrochemotherapy.

Electrochemotherapy is a technique where electric pulses in combination with chemotherapeutic agents are applied to tumor cells. In general, patients find electrochemotherapy tolerable, in spite of unpleasant sensations associated with contraction of muscles located beneath or in the vicinity of the electrodes. These contractions are due to the intensity of the electric pulses required for effective electropermeabilization of tumor cell membranes. Since a train of eight electric pulses with repetition frequency of 1 Hz is usually applied to the tumors, each pulse in the train excites underlying nerves and provokes muscle contractions. Therefore, for patients involved in electrochemotherapy, the use of pulses with repetition frequency higher than the frequency of tetanic contraction would represent reduced number of muscle contractions and associated unpleasant sensations. Our results of the uptake of Lucifer Yellow into electropermeabilized cells in vitro show that with increased repetition frequency the uptake stays at similar levels even at frequencies up to 8.3 kHz. On the basis of these results the possibilities for the clinical use of pulses with high repetition frequency in electrochemotherapy are considered.

Animals↗

PubMed2001

The ratio of single- to double-strand DNA breaks and their absolute values determine cell death pathway.

Bleomycin is a cytotoxic antibiotic that generates DNA double-strand breaks (DSB) and DNA single-strand breaks (SSB). It is possible to introduce known quantities of bleomycin molecules into cells. Low amounts kill the cells by a slow process termed mitotic cell death, while high amounts produce a fast process that has been termed pseudoapoptosis. We previously showed that these types of cell death are a direct consequence of the DSB generated by bleomycin. Here, we use deglyco-bleomycin, a bleomycin derivative lacking the carbohydrate moiety. Although this molecule performs the same nucleophilic attacks on DNA as bleomycin, we show that deglyco-bleomycin is at least 100 times less toxic to Chinese hamster fibroblasts than bleomycin. In fact, deglyco-bleomycin treatment results in apoptosis induction. In contrast, however, deglyco-bleomycin was found to generate almost exclusively SSB. Our results suggest that more than 150 000 SSB per cell are required to trigger apoptosis in Chinese hamster fibroblasts and that SSB are 300 times less toxic than DSB. Taken together with previous studies on bleomycin, our data demonstrates that cells can die by apoptosis, mitotic cell death, or pseudoapoptosis, depending on the number of DNA breaks and on the ratio of SSB to DSB.

Animals↗

PubMed2001

Apoptosis of tumoral and nontumoral lymphoid cells is induced by both mdm2 and p53 antisense oligodeoxynucleotides.

Following stress signals, the p53 tumor suppressor protein plays a critical role in regulation of cell proliferation, mainly through induction of growth arrest or apoptosis. Therefore, this protein needs to be strictly regulated and numerous studies have shown that the MDM2 protein is an essential element for p53 regulation in normal cells and, most importantly, that overexpression of MDM2 is responsible for p53 inactivation in various types of tumors. A previous study showed that this is the case in some Burkitt lymphoma (BL) cell lines, where enhanced translation of mdm2 messenger RNA results in overexpression of the protein that complexes and inactivates wild-type p53. To further investigate the role of the p53/MDM2 complex in these BL cells, as well as in other lymphoid cells that do not overexpress MDM2, this study used antisense oligodeoxynucleotides directed either against mdm2 or against p53. Results show that the mdm2 antisense oligodeoxynucleotide induces apoptosis of cells that express a high or low level of MDM2 protein, only if they contain wild-type p53. Moreover, apoptosis is independent of the accumulation of p53 following mdm2 antisense treatment. Finally, the p53 antisense oligodeoxynucleotide, which inhibits the expression of wild-type p53, also induces a decrease of the MDM2 level in cells, whether or not they overexpress this protein, and causes apoptosis of these cells. These results indicate that decreasing the MDM2 protein level by directly or indirectly targeting its biosynthesis is a potent tool for the induction of apoptosis.

Apoptosis↗

PubMed2001

Slow accumulation of plasmid in muscle cells: supporting evidence for a mechanism of DNA uptake by receptor-mediated endocytosis.

Intramuscular plasmid DNA injection results in long-term but low and variable expression of the injected genes. Optimization is difficult because the mechanism of naked DNA uptake by the cells in vivo is not yet determined. Here we used injections of plasmid DNA encoding luciferase to further characterize this mechanism. We analyzed the kinetics of naked DNA uptake by means of DNase I or heparin injections, using the level of luciferase expression as the indicator of DNA uptake. We demonstrated that in vivo heparin inhibits DNA uptake without affecting the expression of DNA internalized by means of electric pulses. Inhibition by heparin is dose dependent and compatible with the competition for the binding to a receptor. As shown also with DNase I, DNA uptake by muscle cells is slow: a progressive accumulation of the DNA in the myofibers can be found for at least 4 hours after naked DNA injection. Physical presence of DNA molecules during the uptake period, but not later, was confirmed by the facilitation of DNA uptake with appropriate electric pulses. Therefore, uptake proceeds for the entire time during which intact DNA is present in the extracellular compartment. Our results support evidence for a DNA uptake mechanism based on receptor-mediated endocytosis.

Animals↗

PubMed2001

Therapeutic perspectives of in vivo cell electropermeabilization.

Cell electropermeabilization (also termed cell electroporation) is nowadays a routine technique used in biochemical and pharmacological studies for the in vitro introduction of nonpermeant molecules into living cells. But electric pulses can be used as well in vivo for the delivery of drugs or DNA into cells of tissues. This review then gives an updated overview of the therapeutic perspectives of cell electropermeabilization in vivo, in particular of the antitumour electrochemotherapy (i.e., the combination of a cytotoxic nonpermeant drug with permeabilizing electric pulses delivered to the tumours) and of in vivo DNA electrotransfer for gene therapy. After a short summary of the present knowledge on cell electropermeabilization (particularly in vivo), the basis, the present achievements, and the challenges of electrochemotherapy are described and discussed, which includes an overview of still open questions and an update on recent clinical trials. DNA electrotransfer for gene therapy is an emerging field in which results are rapidly accumulating. Present knowledge on DNA electrotransfer mechanisms, as wel as the potentialities of DNA electrotransfer to become an efficient non-viral approach for gene therapy, are reviewed.

Animals↗