Biomedical subjects

J T Boyd

Publications and source records attributed to J T Boyd.

107 records · Page 6Linked to original sources

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).

Journal Article↗

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↗

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↗

PubMed2001

Cloning and characterization of human adenosine 5'-triphosphate-binding cassette, sub-family A, transporter 2 (ABCA2).

We have isolated the full-length cDNA for human ATP-binding cassette, sub-family A, member 2 transporter (ABCA2). The ORF of this cDNA encodes a protein consisting of 2436 amino acids with apparent molecular weight of M(r) 270,000. Accordingly, ABCA2 is the largest known mammalian ABC transporter described thus far. Analysis of mRNA expression levels indicated that ABCA2 is highest in human brain and has a broad expression pattern in a panel of tumor cell lines. Using specific antibodies to ABCA2 and various organelle marker proteins, ABCA2 was found to colocalize with the lysosomal/endosomal marker LAMP1, forming discrete, punctate intracellular vesicles. In ABCA2-transfected cells, the transporter also colocalized with a fluorescently labeled steroid analogue, estramustine. The sequestration of the steroid into the lysosomal/endosomal compartment indicates a potential substrate specificity for ABCA2. Furthermore, the presence of a lipocalin signature motif in the ABCA2 sequence suggests a possible broad role for this protein in the transport of steroids, lipids, and related molecules.

ATP-Binding Cassette Transporters↗

PubMed2001

Chemical agents that promote chromatin compaction radiosensitize tumour cells.

PURPOSE: Previous studies indicated that cells whose chromatin is naturally compacted at the time of radiation are hypersensitive to radiation-induced killing, primarily by single-hit inactivation. Some chemicals that are known to promote chromatin compaction in interphase cells are here investigated for their radiosensitizing potential. MATERIALS AND METHODS: Okadaic acid (OA), a protein phosphatase inhibitor, fostriecin (FC), a topoisomerase II inhibitor and trichostatin A (TSA), a histone deacetylase inhibitor, were reported to promote chromatin compaction in mammalian cells. Asynchronous populations of HT-29 (human colon carcinoma) cells were exposed to various concentrations of OA, FC and TSA for various times before irradiation with various doses of Cs-137 gamma-rays and toxicity and radiosensitization were measured. Induced chromatin compaction was visualized by electron microscopy (EM). Histone 1 (H1) and histone 3 (H3) phosphorylation was measured by Western blotting, whole-cell fluorescence microscopy and confocal microscopy. RESULTS: OA and FC produced significant radiosensitization at 2 Gy after short (2 h) exposures. These chemical treatments also produced increased phosphorylation of H3 and increased chromatin compaction as measured by EM. A 2-h exposure of cells to TSA had no effect on cell radiosensitivity, histone phosphorylation or chromatin condensation. However, a 16-h exposure to TSA produced significant radiosensitization, histone phosphorylation and chromatin condensation, presumably by secondary mechanisms. CONCLUSIONS: These data are consistent with the hypothesis that compacted chromatin is a hypersensitive target for radiation killing. Furthermore, the modulation of chromatin conformation by drugs selectively in tumour cells might radiosensitize tumours whose cells are intrinsically radioresistant.

Alkenes↗

PubMed1999

p21-activated kinase 1 (Pak1) regulates cell motility in mammalian fibroblasts.

The p21 (Cdc42/Rac) activated kinase Pak1 regulates cell morphology and polarity in most, if not all, eukaryotic cells. We and others have established that Pak's effects on these parameters are mediated by changes in the organization of cortical actin. Because cell motility requires polarized rearrangements of the actin/myosin cytoskeleton, we examined the role of Pak1 in regulating cell movement. We established clonal tetracycline-regulated NIH-3T3 cell lines that inducibly express either wild-type Pak1, a kinase-dead, or constitutively-active forms of this enzyme, and examined the morphology, F-actin organization, and motility of these cells. Expression of any of these forms of Pak1 induced dramatic changes in actin organization which were not inhibited by coexpression of a dominant-negative form of Rac1. Cells inducibly expressing wild-type or constitutively-active Pak1 had large, polarized lamellipodia at the leading edge, were more motile than their normal counterparts when plated on a fibronectin-coated surface, and displayed enhanced directional movement in response to an immobilized collagen gradient. In contrast, cells expressing a kinase-dead form of Pak1 projected multiple lamellipodia emerging from different parts of the cell simultaneously. These cells, though highly motile, displayed reduced persistence of movement when plated on a fibronectin-coated surface and had defects in directed motility toward immobilized collagen. Expression of constitutively activated Pak1 was accompanied by increased myosin light chain (MLC) phosphorylation, whereas expression of kinase-dead Pak1 had no effect on MLC. These results suggest that Pak1 affects the phosphorylation state of MLC, thus linking this kinase to a molecule that directly affects cell movement.

3T3 Cells↗

PubMed1998

Amplification of the ATP-binding cassette 2 transporter gene is functionally linked with enhanced efflux of estramustine in ovarian carcinoma cells.

An estramustine-resistant human ovarian carcinoma cell line, SKEM, was generated to explore resistance mechanisms associated with this agent. Cytogenetic analysis revealed that SKEM cells have a homogeneously staining region (hsr) at chromosome 9q34. Microdissection of the hsr, followed by fluorescence in situ hybridization to SKEM and normal metaphase spreads, confirmed that the amplified region was derived from sequences from 9q34. In situ hybridization with a probe specific for ABC2, a gene located at 9q34 that encodes an ATP-binding cassette 2 (ABC2) transporter, indicated that this gene is amplified approximately 6-fold in the estramustine-resistant cells. Southern analysis confirmed that ABC2 was amplified in SKEM, and Northern analysis indicated that the ABC2 transcript was overexpressed approximately 5-fold. The ABC1 gene located at 9q22-31 was not amplified in the resistant cells, and mRNA levels of several other ABC transporter genes were unaltered. Consistent with the concept that increased ABC2 expression contributes to the resistant phenotype, we observed that the rate of efflux of dansylated estramustine was increased in SKEM compared with control cells. In addition, antisense treatment directed toward ABC2 mRNA sensitized the resistant cells to estramustine. Together, these results suggest that amplification and overexpression of ABC2 contributes to estramustine resistance and provides the first indication of a potential cellular function for this product.

ATP-Binding Cassette Transporters↗

PubMed1997

Determinants of nitric oxide in exhaled gas in the isolated rabbit lung.

Nitric oxide concentrations in the exhaled gas (NOe) increases during various inflammatory conditions in humans and animals. Little is known about the sources and factors that influence NOe. NOe at end expiration was measured by chemiluminescence in an isolated, blood-perfused rabbit lung. The average end-expiratory concentration over 10 breaths was used. The effect of positive end-expiratory pressure (PEEP), flow rate, pH, hypoxia, venous pressure, and flow pulsatility on NOe were determined. At constant blood flow, increasing PEEP from 1 to 5 cm H2O elicited a reproducible increase in NOe from 49 +/- 7 to 53 +/- 8 parts per billion (ppb) (p < 0.05). When blood pH was increased from 7.40 to 7.74 by breathing low CO2 gas, NOe rose from 45 +/- 7 to 55 +/- 7 ppb (p < 0.001). Hypoxia caused a dose-dependent decrease in NOe from 37 +/- 3 during baseline to 23 +/- 2 during ventilation with 0% O2 (p < 0.01). Venous pressure elevation from 0 to 5 and 10 mm Hg decreased NOe from 32 +/- 5, to 26 +/- 5 and 24 +/- 5 ppb, respectively (p < 0.05). Switching from steady to pulsatile flow (same man flow) resulted in a small, albeit significant reduction in NOe; 30 +/- 4 to 28 +/- 4 ppb (p < 0.05). Changes in flow rate between 200 and 20 ml/min were associated with small changes in NOe; however, when flow was stopped, NOe rose substantially to 56 +/- 6 ppb (p < 0.05). The changes in NOe were rapid (1 to 2 min) and reversible. The results suggest that NOe is influenced by ventilatory and hemodynamic variables, pH, and hypoxia. We suggest that caution must be taken when interpreting changes in exhaled NO in humans or experimental animals. Changes in total and regional blood flow, capillary blood volume, ventilation, hypoxia, and pH should not be overlooked.

Animals↗

PubMed1973