308 research outputs found
Expression of tissue factor in non-small-cell lung cancers and its relationship to metastasis
Tissue factor (TF) is an initiator of the extrinsic cascade of blood coagulation. Although recent studies have revealed a relationship between metastatic properties and TF expression in some neoplastic cells, the significance of TF in lung cancer, especially in non-small-cell lung cancer (NSCLC), is still unclear. In this study, TF was detected in NSCLC cell lines by functional study, Western blot analysis and immunocytochemical staining. TF levels in eight NSCLC cell lines were also quantitated by enzyme-linked immunosorbent assay (ELISA), and TF expression was evaluated in 55 specimens of surgically resected NSCLCs. NSCLC cell lines derived from metastatic lesions produced high levels of TF (48.3 ± 23.5 ng 10â6 cells, mean ± s.e.m.), whereas those derived from primary lesions produced low levels of TF (0.2 ± 0.1 ng 10â6 cells). Immunohistochemical studies disclosed significantly stronger staining for TF in cells from NSCLC patients with metastasis than in those without metastasis. Among the 28 patients with metastasis, ten were strongly positive, 16 were moderately positive and two were negative for TF. In contrast, among the 27 patients without metastasis, only two were strongly positive, 18 were moderately positive and seven were negative for TF. Therefore, malignant cells from patients with lung cancer produce various levels of TF, and TF may play an important role in the metastatic process. © 1999 Cancer Research Campaig
Neutrino masses from new generations
We reconsider the possibility that Majorana masses for the three known
neutrinos are generated radiatively by the presence of a fourth generation and
one right-handed neutrino with Yukawa couplings and a Majorana mass term. We
find that the observed light neutrino mass hierarchy is not compatible with low
energy universality bounds in this minimal scenario, but all present data can
be accommodated with five generations and two right-handed neutrinos. Within
this framework, we explore the parameter space regions which are currently
allowed and could lead to observable effects in neutrinoless double beta decay,
conversion in nuclei and experiments. We
also discuss the detection prospects at LHC.Comment: 28 pages, 4 figures. Version to be published. Some typos corrected.
Improved figures 3 and
Pharmacokinetics and metabolism of 13-cis-retinoic acid (isotretinoin) in children with high-risk neuroblastoma â a study of the United Kingdom Children's Cancer Study Group
The administration of 13-cis-retinoic acid (13-cisRA), following myeloablative therapy improves 3-year event-free survival rates in children with high-risk neuroblastoma. This study aimed to determine the degree of inter-patient pharmacokinetic variation and extent of metabolism in children treated with 13-cisRA. 13-cis-retinoic acid (80âmgâmâ2 b.d.) was administered orally and plasma concentrations of parent drug and metabolites determined on days 1 and 14 of courses 2, 4 and 6 of treatment. Twenty-eight children were studied. The pharmacokinetics of 13-cisRA were best described by a modified one-compartment, zero-order absorption model combined with lag time. Mean population pharmacokinetic parameters included an apparent clearance of 15.9âlâhâ1, apparent volume of distribution of 85âl and absorption lag time of 40âmin with a large inter-individual variability associated with all parameters (coefficients of variation greater than 50%). Day 1 peak 13-cisRA levels and exposure (AUC) were correlated with method of administration (P<0.02), with 2.44- and 1.95-fold higher parameter values respectively, when 13-cisRA capsules were swallowed as opposed to being opened and the contents mixed with food before administration. Extensive accumulation of 4-oxo-13-cisRA occurred during each course of treatment with plasma concentrations (mean±s.d. 4.67±3.17âÎŒM) higher than those of 13-cisRA (2.83±1.44âÎŒM) in 16 out of 23 patients on day 14 of course 2. Extensive metabolism to 4-oxo-13-cisRA may influence pharmacological activity of 13-cisRA
Integrating isotopes and documentary evidence : dietary patterns in a late medieval and early modern mining community, Sweden
We would like to thank the Archaeological Research Laboratory, Stockholm University, Sweden and the Tandem Laboratory (Ă
ngström Laboratory), Uppsala University, Sweden, for undertaking the analyses of stable nitrogen and carbon isotopes in both human and animal collagen samples. Also, thanks to Elin Ahlin Sundman for providing the ÎŽ13C and ÎŽ15N values for animal references from VĂ€sterĂ„s. This research (BĂ€ckströmâs PhD employment at Lund University, Sweden) was supported by the Berit Wallenberg Foundation (BWS 2010.0176) and Jakob and Johan Söderbergâs foundation. The âSala projectâ (excavations and analyses) has been funded by Riksens Clenodium, Jernkontoret, Birgit and Gad Rausingâs Foundation, SAUâs Research Foundation, the Royal Physiographic Society of Lund, Berit Wallenbergs Foundation, Ă
ke Wibergs Foundation, Lars Hiertas Memory, Helge Ax:son Johnsonâs Foundation and The Royal Swedish Academy of Sciences.Peer reviewedPublisher PD
Recommended from our members
Improved Constraints on Sterile Neutrino Mixing from Disappearance Searches in the MINOS, MINOS+, Daya Bay, and Bugey-3 Experiments.
Searches for electron antineutrino, muon neutrino, and muon antineutrino disappearance driven by sterile neutrino mixing have been carried out by the Daya Bay and MINOS+ collaborations. This Letter presents the combined results of these searches, along with exclusion results from the Bugey-3 reactor experiment, framed in a minimally extended four-neutrino scenario. Significantly improved constraints on the Ξ_{ÎŒe} mixing angle are derived that constitute the most constraining limits to date over five orders of magnitude in the mass-squared splitting Îm_{41}^{2}, excluding the 90% C.L. sterile-neutrino parameter space allowed by the LSND and MiniBooNE observations at 90% CL_{s} for Îm_{41}^{2}<13ââeV^{2}. Furthermore, the LSND and MiniBooNE 99% C.L. allowed regions are excluded at 99% CL_{s} for Îm_{41}^{2}<1.6âeV^{2}
Recommended from our members
First measurement of neutrino oscillation parameters using neutrinos and antineutrinos by NOvA.
The NOvA experiment has seen a 4.4Ï signal of Îœ[over ÂŻ]_{e} appearance in a 2 GeV Îœ[over ÂŻ]_{ÎŒ} beam at a distance of 810 km. Using 12.33Ă10^{20} protons on target delivered to the Fermilab NuMI neutrino beamline, the experiment recorded 27 Îœ[over ÂŻ]_{ÎŒ}âÎœ[over ÂŻ]_{e} candidates with a background of 10.3 and 102 Îœ[over ÂŻ]_{ÎŒ}âÎœ[over ÂŻ]_{ÎŒ} candidates. This new antineutrino data are combined with neutrino data to measure the parameters |Îm_{32}^{2}|=2.48_{-0.06}^{+0.11}Ă10^{-3}ââeV^{2}/c^{4} and sin^{2}Ξ_{23} in the ranges from (0.53-0.60) and (0.45-0.48) in the normal neutrino mass hierarchy. The data exclude most values near ÎŽ_{CP}=Ï/2 for the inverted mass hierarchy by more than 3Ï and favor the normal neutrino mass hierarchy by 1.9Ï and Ξ_{23} values in the upper octant by 1.6Ï
Search for sterile neutrino mixing in the MINOS long-baseline experiment
A search for depletion of the combined flux of active neutrino species over a 735 km baseline is reported using neutral-current interaction data recorded by the MINOS detectors in the NuMI neutrino beam. Such a depletion is not expected according to conventional interpretations of neutrino oscillation data involving the three known neutrino flavors. A depletion would be a signature of oscillations or decay to postulated noninteracting sterile neutrinos, scenarios not ruled out by existing data. From an exposure of 3.18Ă1020 protons on target in which neutrinos of energies between ~500¿¿MeV and 120 GeV are produced predominantly as ¿”, the visible energy spectrum of candidate neutral-current reactions in the MINOS far detector is reconstructed. Comparison of this spectrum to that inferred from a similarly selected near-detector sample shows that of the portion of the ¿” flux observed to disappear in charged-current interaction data, the fraction that could be converting to a sterile state is less than 52% at 90% confidence level (C.L.). The hypothesis that active neutrinos mix with a single sterile neutrino via oscillations is tested by fitting the data to various models. In the particular four-neutrino models considered, the mixing angles Âż24 and Âż34 are constrained to be less than 11° and 56° at 90% C.L., respectively. The possibility that active neutrinos may decay to sterile neutrinos is also investigated. Pure neutrino decay without oscillations is ruled out at 5.4 standard deviations. For the scenario in which active neutrinos decay into sterile states concurrently with neutrino oscillations, a lower limit is established for the neutrino decay lifetime t3/m3>2.1Ă10-12¿¿s/eV at 90% C.L
Recommended from our members
Observation of seasonal variation of atmospheric multiple-muon events in the NOvA Near Detector
Using two years of data from the NOvA Near Detector at Fermilab, we report a seasonal variation of cosmic ray induced multiple-muon (NÎŒâ„2) event rates which has an opposite phase to the seasonal variation in the atmospheric temperature. The strength of the seasonal multiple-muon variation is shown to increase as a function of the muon multiplicity. However, no significant dependence of the strength of the seasonal variation of the multiple-muon variation is seen as a function of the muon zenith angle, or the spatial or angular separation between the correlated muons
Localization and potential role of matrix metalloproteinase-1 and tissue inhibitors of metalloproteinase-1 and -2 in different phases of bronchopulmonary dysplasia
Bronchopulmonary dysplasia (BPD) can evolve in prematurely born infants
who require mechanical ventilation because of hyaline membrane disease
(HMD). The development of BPD can be divided in an acute, a regenerative,
a transitional, and a chronic phase. During these different phases,
extensive remodeling of the lung parenchyma with re-epithelialization of
the alveoli and formation of fibrosis occurs. Matrix metalloproteinase-1
(MMP-1) is an enzyme that is involved in re-epithelialization processes,
and dysregulation of MMP-1 activity contributes to fibrosis. Localization
of MMP-1 and its inhibitors, tissue inhibitor of metalloproteinase
(TIMP)-1 and TIMP-2, were investigated in lung tissue obtained from
infants who died during different phases of BPD development. In all
studied cases (n = 50) type-II pneumocytes were found to be immunoreactive
for MMP-1, TIMP-1, and TIMP-2. During the acute and regenerative phase of
BPD, type-II pneumocytes re-epithelialize the injured alveoli. This may
suggest that MMP-1 and its inhibitors, expressed by type-II pneumocytes,
play a role in the re-epithelialization process after acute lung injury.
Although MMP-1 staining intensity remained constant in type-II pneumocytes
during BPD development, TIMP-1 increased during the chronic fibrotic
phase. This relative elevation of TIMP-1 compared with MMP-1 is indicative
for reduced collagenolytic activity by type-II pneumocytes in chronic BPD
and may contribute to fibrosis. Fibrotic foci in chronic BPD contained
fibroblasts immunoreactive for MMP-1 and TIMP-1 and -2. This may indicate
that decreased collagen turnover by fibroblasts contributes to fibrosis in
BPD development
- âŠ