Showing papers by "Takashi Saito published in 2010"

Magic gamma-ray telescope observation of the perseus cluster of galaxies : implications for cosmic rays, dark matter, and ngc 1275

Abstract: The Perseus galaxy cluster was observed by the MAGIC Cherenkov telescope for a total effective time of 24.4 hr during 2008 November and December. The resulting upper limits on the gamma-ray emission above 100 GeV are in the range of 4.6-7.5 x 10(-12) cm(-2) s(-1) for spectral indices from -1.5 to -2.5, thereby constraining the emission produced by cosmic rays, dark matter annihilations, and the central radio galaxy NGC 1275. Results are compatible with cosmological cluster simulations for the cosmic-ray-induced gamma-ray emission, constraining the average cosmic ray-to-thermal pressure to < 4% for the cluster core region (< 8% for the entire cluster).

The immunological synapse, TCR microclusters, and T cell activation.

Abstract: T cell activation begins with the interaction between an antigen-specific T cell and an antigen-presenting cell (APC). This interaction results in the formation of the immunological synapse, which had been considered to be responsible for antigen recognition and T cell activation. Recent advances in imaging analysis have provided new insights into T cell activation. The T cell receptor (TCR) microclusters, TCRs, kinases, and adaptors are generated upon antigen recognition at the interfaces between the T cells and the APCs and serve as a fundamental signaling unit for T cell activation. CD28-mediated costimulation is also found to be regulated by the formation of microclusters. Therefore, the dynamic regulations of TCR and CD28 microcluster formation, migration, and interaction are the key events for the initiation of T cell-mediated immune responses. Comprehensive analyses of the composition and characteristics of the TCR microcluster have identified its dynamic features. This review will outline new discoveries of the microclusters and its related concept in T cell activation.

Evidence for superconducting gap nodes in the zone-centered hole bands of KFe2As2 from magnetic penetration-depth measurements

Abstract: Among the iron-based pnictide superconductors the material ${\text{KFe}}_{2}{\text{As}}_{2}$ is unusual in that its Fermi surface does not consist of quasinested electron and hole pockets. Here we report measurements of the temperature dependent London penetration depth of very clean crystals of this compound with residual resistivity ratio $g1200$. We show that the superfluid density at low temperatures exhibits a strong linear-in-temperature dependence which implies that there are line nodes in the energy gap on the large zone-centered hole sheets. The results indicate that ${\text{KFe}}_{2}{\text{As}}_{2}$ is an unconventional superconductor with strong electron correlations.

DETECTION OF VERY HIGH ENERGY γ-RAY EMISSION FROM THE PERSEUS CLUSTER HEAD-TAIL GALAXY IC 310 BY THE MAGIC TELESCOPES

Abstract: We report on the detection with the MAGIC telescopes of very high energy (VHE) gamma-rays from IC 310, a head-tail radio galaxy in the Perseus galaxy cluster, observed during the interval 2008 November to 2010 February. The Fermi satellite has also detected this galaxy. The source is detected by MAGIC at a high statistical significance of 7.6 sigma in 20.6 hr of stereo data. The observed spectral energy distribution is flat with a differential spectral index of -2.00 +/- 0.14. The mean flux above 300 GeV, between 2009 October and 2010 February, (3.1 +/- 0.5) x 10(-12) cm(-2) s(-1), corresponds to (2.5 +/- 0.4)% of Crab Nebula units. Only an upper limit, of 1.9% of Crab Nebula units above 300 GeV, was obtained with the 2008 data. This, together with strong hints (>3 sigma) of flares in the middle of 2009 October and November, implies that the emission is variable. The MAGIC results favor a scenario with the VHE emission originating from the inner jet close to the central engine. More complicated models than a simple one-zone synchrotron self-Compton (SSC) scenario, e. g., multi-zone SSC, external Compton, or hadronic, may be required to explain the very flat spectrum and its extension over more than three orders of magnitude in energy.

Detection of very high energy gamma-ray emission from the Perseus cluster head-tail galaxy IC 310 by the MAGIC telescopes

Abstract: We report on the detection with the MAGIC telescopes of very high energy gamma-rays from IC 310, a head-tail radio galaxy in the Perseus galaxy cluster, observed during the interval November 2008 to February 2010. The Fermi satellite has also detected this galaxy. The source is detected by MAGIC at a high statistical significance of 7.6sigma in 20.6 hr of stereo data. The observed spectral energy distribution is flat with a differential spectral index of -2.00 \pm 0.14. The mean flux above 300 GeV, between October 2009 and February 2010, (3.1 \pm 0.5)x10^{-12} cm^{-2} s^{-1}, corresponds to (2.5 \pm 0.4)% of Crab Nebula units. Only an upper limit, of 1.9% of Crab Nebula units above 300 GeV, was obtained with the 2008 data. This, together with strong hints (>3sigma) of flares in the middle of October and November 2009, implies that the emission is variable. The MAGIC results favour a scenario with the very high energy emission originating from the inner jet close to the central engine. More complicated models than a simple one-zone SSC scenario, e.g. multi-zone SSC, external Compton or hadronic, may be required to explain the very flat spectrum and its extension over more than three orders of magnitude in energy.

Search for an extended VHE gamma-ray emission from Mrk 421 and Mrk 501 with the MAGIC Telescope

Abstract: Context. Part of the very high energy -ray radiation coming from extragalactic sources is absorbed through the pair production process on the extragalactic background light photons. Extragalacti c magnetic fields alter the trajectories of these cascade pai rs and, in turn, convert cosmic background photons to gamma-ray energies by inverse Compton scattering. These secondary photons can form an extended halo around bright VHE sources. Aims. We searched for an extended emission around the bright blazars Mrk 421 and Mrk 501 using the MAGIC telescope data. Methods. If extended emission is present, the angular distribution o f reconstructed gamma-ray arrival directions around the source is broader than for a point-like source. In the analysis of a few tens of hours of observational data taken from Mrk 421 and Mrk 501 we used a newly developed method that provides better angular resolution. This method is based on the usage of multidimensional decision trees. Comparing the measured shapes of angular distributions with those expected from a point-like source one can detect or constrain possible exten ded emission around the source. We also studied the influence of di fferent types of systematic errors on the shape of the distribu tion of reconstructed gamma-ray arrival directions for a point source. Results. We present upper limits for an extended emission calculated for both sources for various source extensions and emission profiles. We obtain upper limits on the extended emission around the Mrk 421 (Mrk 501) on the level of < 5% (< 4% ) of the Crab Nebula flux above the energy threshold of 300 GeV. Using these results we discuss possible constraints on the extragalactic magnetic fields st rength around a few times 10 −15 G.

T-Cell Receptor Microclusters Critical for T-Cell Activation Are Formed Independently of Lipid Raft Clustering

Abstract: We studied the function of lipid rafts in generation and signaling of T-cell receptor microclusters (TCR-MCs) and central supramolecular activation clusters (cSMACs) at immunological synapse (IS). It has been suggested that lipid raft accumulation creates a platform for recruitment of signaling molecules upon T-cell activation. However, several lipid raft probes did not accumulate at TCR-MCs or cSMACs even with costimulation and the fluorescence resonance energy transfer (FRET) between TCR or LAT and lipid raft probes was not induced at TCR-MCs under the condition of positive induction of FRET between CD3ζ and ZAP-70. The analysis of LAT mutants revealed that raft association is essential for the membrane localization but dispensable for TCR-MC formation. Careful analysis of the accumulation of raft probes in the cell interface revealed that their accumulation occurred after cSMAC formation, probably due to membrane ruffling and/or endocytosis. These results suggest that lipid rafts control protein translocation to the membrane but are not involved in the clustering of raft-associated molecules and therefore that the lipid rafts do not serve as a platform for T-cell activation.

Antisense PMO Found in Dystrophic Dog Model Was Effective in Cells from Exon 7-Deleted DMD Patient

Abstract: Background Antisense oligonucleotide-induced exon skipping is a promising approach for treatment of Duchenne muscular dystrophy (DMD). We have systemically administered an antisense phosphorodiamidate morpholino oligomer (PMO) targeting dystrophin exons 6 and 8 to a dog with canine X-linked muscular dystrophy in Japan (CXMDJ) lacking exon 7 and achieved recovery of dystrophin in skeletal muscle. To date, however, antisense chemical compounds used in DMD animal models have not been directly applied to a DMD patient having the same type of exon deletion. We recently identified a DMD patient with an exon 7 deletion and tried direct translation of the antisense PMO used in dog models to the DMD patient's cells. Methodology/Principal Findings We converted fibroblasts of CXMDJ and the DMD patient to myotubes by FACS-aided MyoD transduction. Antisense PMOs targeting identical regions of dog and human dystrophin exons 6 and 8 were designed. These antisense PMOs were mixed and administered as a cocktail to either dog or human cells in vitro. In the CXMDJ and human DMD cells, we observed a similar efficacy of skipping of exons 6 and 8 and a similar extent of dystrophin protein recovery. The accompanying skipping of exon 9, which did not alter the reading frame, was different between cells of these two species. Conclusion/Significance Antisense PMOs, the effectiveness of which has been demonstrated in a dog model, achieved multi-exon skipping of dystrophin gene on the FACS-aided MyoD-transduced fibroblasts from an exon 7-deleted DMD patient, suggesting the feasibility of systemic multi-exon skipping in humans.

MAGIC TeV gamma-ray observations of Markarian 421 during multiwavelength campaigns in 2006

Abstract: Context. Wide-range spectral coverage of blazar-type active galactic nuclei is of paramount importance for understanding the particle acceleration mechanisms assumed to take place in their jets. The Major Atmospheric Gamma Imaging Cerenkov (MAGIC) telescope participated in three multiwavelength (MWL) campaigns, observing the blazar Markarian (Mkn) 421 during the nights of April 28 and 29, 2006, and June 14, 2006. Aims. We analyzed the corresponding MAGIC very-high energy observations during 9 nights from April 22 to 30, 2006 and on June 14, 2006. We inferred light curves with sub-day resolution and night-by-night energy spectra. Methods. MAGIC detects gamma-rays by observing extended air showers in the atmosphere. The obtained air-shower images were analyzed using the standard MAGIC analysis chain. Results. A strong gamma-ray signal was detected from Mkn 421 on all observation nights. The flux (E > 250 GeV) varied on night-by-night basis between (0.92 +/- 0.11) x 10(-10) cm(-2) s(-1) (0.57 Crab units) and (3.21 +/- 0.15) x 10(-10) cm(-2) s(-1) (2.0 Crab units) in April 2006. There is a clear indication for intra-night variability with a doubling time of 36 +/- 10(stat) min on the night of April 29, 2006, establishing once more rapid flux variability for this object. For all individual nights gamma-ray spectra could be inferred, with power-law indices ranging from 1.66 to 2.47. We did not find statistically significant correlations between the spectral index and the flux state for individual nights. During the June 2006 campaign, a flux substantially lower than the one measured by the Whipple 10-m telescope four days later was found. Using a log-parabolic power law fit we deduced for some data sets the location of the spectral peak in the very-high energy regime. Our results confirm the indications of rising peak energy with increasing flux, as expected in leptonic acceleration models.

ON TEMPORAL VARIATIONS OF THE MULTI-TeV COSMIC RAY ANISOTROPY USING THE TIBET III AIR SHOWER ARRAY

Abstract: We analyze the large-scale two-dimensional sidereal anisotropy of multi-TeV cosmic rays (CRs) by the Tibet Air Shower Array, with the data taken from 1999 November to 2008 December. To explore temporal variations of the anisotropy, the data set is divided into nine intervals, each with a time span of about one year. The sidereal anisotropy of magnitude, about 0.1%, appears fairly stable from year to year over the entire observation period of nine years. This indicates that the anisotropy of TeV Galactic CRs remains insensitive to solar activities since the observation period covers more than half of the 23rd solar cycle.

Observations of the Blazar 3C 66A with the MAGIC Telescopes in Stereoscopic Mode

Abstract: We report new observations of the intermediate-frequency peaked BL Lacertae object 3C 66A with the MAGIC telescopes. The data sample we use were taken in 2009 December and 2010 January, and comprises 2.3 hr of good quality data in stereoscopic mode. In this period, we find a significant signal from the direction of the blazar 3C 66A. The new MAGIC stereoscopic system is shown to play an essential role for the separation between 3C 66A and the nearby radio galaxy 3C 66B, which is at a distance of only $6^\prime$. The derived integral flux above $100\eh{GeV}$ is 8.3% of Crab Nebula flux and the energy spectrum is reproduced by a power law of photon index $3.64 \pm 0.39_{\rm stat} \pm 0.25_{\rm sys}$. Within errors, this is compatible with the one derived by VERITAS in 2009. From the spectra corrected for absorption by the extragalactic background light, we only find small differences between the four models that we applied, and constrain the redshift of the blazar to $z < 0.68$.

MAGIC TeV Gamma-Ray Observations of Markarian 421 during Multiwavelength Campaigns in 2006

Abstract: The Major Atmospheric Gamma Imaging Cerenkov (MAGIC) telescope participated in three multiwavelength (MWL) campaigns, observing the blazar Markarian (Mkn) 421 during the nights of 2006 April 28, 29, and 2006 June 14. We analyzed the corresponding MAGIC very-high energy observations during 9 nights from 2006 April 22 to 30 and on 2006 June 14. We inferred light curves with sub-day resolution and night-by-night energy spectra. A strong gamma-ray signal was detected from Mkn 421 on all observation nights. The flux (E > 250 GeV) varied on night-by-night basis between (0.92+-0.11)10^-10 cm^-2 s^-1 (0.57 Crab units) and (3.21+-0.15)10^-10 cm^-2 s^-1 (2.0 Crab units) in 2006 April. There is a clear indication for intra-night variability with a doubling time of 36+-10(stat) minutes on the night of 2006 April 29, establishing once more rapid flux variability for this object. For all individual nights gamma-ray spectra could be inferred, with power-law indices ranging from 1.66 to 2.47. We did not find statistically significant correlations between the spectral index and the flux state for individual nights. During the June 2006 campaign, a flux substantially lower than the one measured by the Whipple 10-m telescope four days later was found. Using a log-parabolic power law fit we deduced for some data sets the location of the spectral peak in the very-high energy regime. Our results confirm the indications of rising peak energy with increasing flux, as expected in leptonic acceleration models.

On Temporal Variations of the Multi-TeV Cosmic Ray Anisotropy using the Tibet III Air Shower Array

Abstract: We analyze the large-scale two-dimensional sidereal anisotropy of multi-TeV cosmic rays by Tibet Air Shower Array, with the data taken from 1999 November to 2008 December. To explore temporal variations of the anisotropy, the data set is divided into nine intervals, each in a time span of about one year. The sidereal anisotropy of magnitude about 0.1% appears fairly stable from year to year over the entire observation period of nine years. This indicates that the anisotropy of TeV Galactic cosmic rays remains insensitive to solar activities since the observation period covers more than a half of the 23rd solar cycle.

Simultaneous multi-frequency observation of the unknown redshift blazar PG 1553+113 in March-April 2008

Abstract: The blazar PG 1553+113 is a well known TeV -ray emitter. In this paper we determine its spectral energy distribution through simultaneous multi-frequency data to study its emission processes. An extensive campaign was carried out between March and April 2008, where optical, X-ray, high-energy (HE) -ray, and very-high-energy (VHE) -ray data were obtained with the KVA, Abastumani, REM, RossiXTE/ASM, AGILE and MAGIC telescopes, respectively. We combine the data to derive the source’s spectral energy distribution and interpret its double-peaked shape within the framework of a synchrotron self-Compton model.

Gamma-ray excess from a stacked sample of high- and intermediate-frequency peaked blazars observed with the MAGIC telescope

Abstract: Between 2004 and 2009 a sample of 28 X-ray selected high- and intermediate-frequency peaked blazars with a X-ray flux larger than 2 uJy at 1 keV in the redshift range from 0.018 to 0.361 was observed with the MAGIC telescope at energies above 100 GeV. Seven among them were detected and the results of these observations are discussed elsewhere. Here we concentrate on the remaining 21 blazars which were not detected during this observation campaign and present the 3 sigma (99.7 %) confidence upper limits on their flux. The individual flux upper limits lie between 1.6 % and 13.6 % of the integral flux from the Crab Nebula. Applying a stacking method to the sample of non-detections with a total of 394.1 hours exposure time, we find evidence for an excess with a cumulative significance of 4.9 standard deviations. It is not dominated by individual objects or flares, but increases linearly with the observation time as for a constant source with an integral flux level of ~1.5 % of that observed from the Crab Nebula above 150 GeV.

OBSERVATION OF TeV GAMMA RAYS FROM THE FERMI BRIGHT GALACTIC SOURCES WITH THE TIBET AIR SHOWER ARRAY

Abstract: Using the Tibet-III air shower array, we search for TeV γ-rays from 27 potential Galactic sources in the early list of bright sources obtained by the Fermi Large Area Telescope at energies above 100 MeV. Among them, we observe seven sources instead of the expected 0.61 sources at a significance of 2σ or more excess. The chance probability from Poisson statistics would be estimated to be 3.8 × 10–6. If the excess distribution observed by the Tibet-III array has a density gradient toward the Galactic plane, the expected number of sources may be enhanced in chance association. Then, the chance probability rises slightly, to 1.2 × 10–5, based on a simple Monte Carlo simulation. These low chance probabilities clearly show that the Fermi bright Galactic sources have statistically significant correlations with TeV γ-ray excesses. We also find that all seven sources are associated with pulsars, and six of them are coincident with sources detected by the Milagro experiment at a significance of 3σ or more at the representative energy of 35 TeV. The significance maps observed by the Tibet-III air shower array around the Fermi sources, which are coincident with the Milagro ≥3σ sources, are consistent with the Milagro observations. This is the first result of the northern sky survey of the Fermi bright Galactic sources in the TeV region.

MAGIC observation of the GRB080430 afterglow

Abstract: Context: Gamma-ray bursts are cosmological sources emitting radiation from the gamma-rays to the radio band. Substantial observational efforts have been devoted to the study of gamma-ray bursts during the prompt phase, i.e. the initial burst of high-energy radiation, and during the long-lasting afterglows. In spite of many successes in interpreting these phenomena, there are still several open key questions about the fundamental emission processes, their energetics and the environment. Aim: Independently of specific gamma-ray burst theoretical recipes, spectra in the GeV/TeV range are predicted to be remarkably simple, being satisfactorily modeled with power-laws, and therefore offer a very valuable tool to probe the extragalactic background light distribution. Furthermore, the simple detection of a component at very-high energies, i.e. at $\sim 100$\,GeV, would solve the ambiguity about the importance of various possible emission processes, which provide barely distinguishable scenarios at lower energies. Methods: We used the results of the MAGIC telescope observation of the moderate resdhift ($z\sim0.76$) \object{GRB\,080430} at energies above about 80\,GeV, to evaluate the perspective for late-afterglow observations with ground based GeV/TeV telescopes. Results: We obtained an upper limit of $F_{\rm 95%\,CL} = 5.5 \times 10^{-11}$\,erg\,cm$^{-2}$\,s$^{-1}$ for the very-high energy emission of \object{GRB\,080430}, which cannot set further constraints on the theoretical scenarios proposed for this object also due to the difficulties in modeling the low-energy afterglow. Nonetheless, our observations show that Cherenkov telescopes have already reached the required sensitivity to detect the GeV/TeV emission of GRBs at moderate redshift ($z \lesssim 0.8$), provided the observations are carried out at early times, close to the onset of their afterglow phase.

Search for very high energy gamma-ray emission from pulsar-pulsar wind nebula systems with the magic telescope

Abstract: The MAGIC collaboration has searched for high-energy gamma-ray emission of some of the most promising pulsar candidates above an energy threshold of 50 GeV, an energy not reachable up to now by other ground-based instruments. Neither pulsed nor steady gamma-ray emission has been observed at energies of 100 GeV from the classical radio pulsars PSR J0205+6449 and PSR J2229+6114 (and their nebulae 3C58 and Boomerang, respectively) and the millisecond pulsar PSR J0218+4232. Here, we present the flux upper limits for these sources and discuss their implications in the context of current model predictions.

Magnetic coupling between A ′ and B sites in the A -site-ordered perovskite BiCu 3 Mn 4 O 12

Abstract: The ionic states of Cu and Mn ions and the magnetic structure in an $A$-site-ordered perovskite ${\text{BiCu}}_{3}{\text{Mn}}_{4}{\text{O}}_{12}$ were investigated by powder neutron diffraction and soft x-ray absorption and magnetic circular dichroism spectroscopy experiments. A substitution by ${\text{Mn}}^{3+}$ was found at the square-planar ${A}^{\ensuremath{'}}$ ${\text{Cu}}^{2+}$ site, leading to a composition $\text{Bi}{(\text{Cu}^{2+}{}_{0.8}\text{Mn}^{3+}{}_{0.2})}_{3}\text{Mn}^{3.6+}{}_{4}{\text{O}}_{12}$. This compound is a ferrimagnet with a collinear spin configuration below ${T}_{\text{C}}=350\text{ }\text{K}$, and the magnetic structure is stabilized by a strong ferromagnetic coupling between the ${A}^{\ensuremath{'}}$ and $B$ site Mn ions and an antiferromagnetic coupling between Cu and Mn ions, leading to a near zero net moment at the ${A}^{\ensuremath{'}}$ site.

Activation-induced accumulation of B and T lymphocyte attenuator at the immunological synapse in CD4+ T cells

Abstract: BTLA, a recently cloned coreceptor expressed on lymphocytes, negatively regulates cell activation by recruiting SHP-1/SHP-2. However, the mechanisms that regulate the intracellular localization of BTLA and its trafficking to the cell surface in T cells are still unknown. To determine the mechanisms that regulate the expression of BTLA on the surface of T cells, we examined the subcellular localization of BTLA in mouse T cells in a steady state, as well as upon activation by using a confocal laser-scanning microscopy. We found that BTLA was localized mainly in the Golgi apparatus and secretory lysosomes in resting CD4(+) T cells. We also found that intracellular BTLA was translocated to the cell surface and accumulated at the immunological synapse upon TCR stimulation. Furthermore, we found that the BTLA-HVEM interaction was required for the association of BTLA with lipid rafts. These results indicate that the surface expression of BTLA and its accumulation at the immunological synapse are tightly regulated by TCR and HVEM stimulation to deliver efficient inhibitory signals in the regulation of CD4(+) T cell activation.

Germ-line elimination of electric charge on pre-T-cell receptor (TCR) impairs autonomous signaling for β-selection and TCR repertoire formation

Abstract: The pre–T-cell receptor (TCR) is crucial for the early T-cell development, but the ligand for pre-TCR remains unidentified. We recently proposed a model that pre-TCR complexes oligomerize spontaneously through interactions of the pre-TCRα chain. To investigate the mechanism underlying this ligand-independent signaling in vivo, we established knock-in mice that express a pre-TCRα mutant lacking charged amino acids (D22R24R102R117 to A22A24A102A117; 4A). CD4+CD8+ thymocyte number was significantly reduced in invariant pre-TCRα (pTα4A/4A) mice, whereas CD4−CD8− thymocytes were unaffected. The percentages of double-negative 3 (DN3) cells and γδ T cells were increased in the pTα4A/4A thymus, indicating that β-selection is impaired in pTα4A/4A mice. Pre-TCR–mediated tyrosine phosphorylation and clonal expansion into double-positive thymocytes were also defective in the knock-in mice. Pre-TCR was expressed at higher levels on pTα4A/4A cell surfaces than on those of the wild type, suggesting that the charged residues in pTα are critical for autonomous engagement and subsequent internalization of pre-TCR. Pre-TCR–mediated allelic exclusion of the TCRβ gene was also inhibited in pTα4A/4A mice, and thereby, dual TCRβs were expressed on pTα4A/4A T cells. Furthermore, the TCRβ chain variable region (Vβ) repertoire of mature T cells was significantly altered in pTα4A/4A mice. These results suggest that charged residues of pTα are critical for β-selection, allelic exclusion, and TCRβ repertoire formation.

Quasi-Two-Dimensional Fermi Surfaces and Coherent Interlayer Transport in KFe 2 As 2

Abstract: We report the results of the angular-dependent magnetoresistance oscillations (AMROs), which can determine the shape of bulk Fermi surfaces (FSs) in quasi-two-dimensional (Q2D) systems, in a highly hole-doped Fe-based superconductor ${\mathrm{KFe}}_{2}{\mathrm{As}}_{2}$ with ${T}_{c}\ensuremath{\approx}3.7\text{ }\text{ }\mathrm{K}$. From the AMROs, we determined the two Q2D FSs with rounded-square cross sections, correspond to 12% and 17% of the first Brillouin zone. The rounded-squared shape of the FS cross section is also confirmed by the analyses of the interlayer transport under in-plane fields. From the obtained FS shape, we infer the character of the $3d$ orbitals that contribute to the FSs.

Dendritic Cell Differentiation and Tumor Cell Apoptosis Induced by Components of a Poly-phenylpropanoid Polysaccharide Complex

Abstract: Background: As part of the indigenous folk medicine in Japan, aqueous extracts of pine cones have been used for over a century to treat cancer and other illnesses and references to their use can be found in ancient Greek literature. However, the mechanisms by which such extracts work are largely unknown. Materials and Methods: Murine bone marrow (BM)-derived dendritic cells (DCs) and human monocyte U937 cells were treated in vitro with an extract prepared from pine cones (termed poly-phenylpropanoid polysaccharide complex, PPC). Results: The components of the PPC were separated into different molecular weight fractions with distinct biological activities. One fraction, consisting of relatively high molecular weight material, was found to induce the differentiation of murine BM cells into immature DC, as well as the maturation of immature DCs into mature DCs. A second fraction, consisting of low molecular weight material, was found to inhibit the in vitro growth of the U937 cells and two other human cancer cell lines. The inhibition of tumor cell growth was found to be associated with the generation of reactive oxygen species (ROS) and the induction of a mitochondria-dependent apoptotic pathway. Conclusion: The effects on dendritic cells and the inhibition of tumor growth, if they occur to a significant level in vivo, could help explain the apparent usefulness of PPC in the treatment of cancer.

A heat-stable extract from Mucuna stimulates the differentiation of bone marrow cells into dendritic cells and induces apoptosis in cancer cells.

Abstract: Pine cone extract is known to induce differentiation of human mononuclear cells into dendritic cells (DCs) and also to induce apoptosis in human cancer cells. In the present study, we screened edible plants that contain components with biological activities similar to or more potent than those of pine cone extract. We found that Mucuna (Mucuna pruviens var. utilis) contains a DC differentiation/maturation-inducing activity and a component that induces apoptosis in human cancer cell lines. Mucuna extract specifically stimulated differentiation of BM cells to immature DCs. Marked production of IL-6 was observed by sequential treatment with at least 10 μg/mL of Mucuna extract followed by LPS. The sequential treatment with Mucuna extract followed by LPS produced a much higher ratio of IL-12 to IL-6 and a lower ratio of TNF-α to IL-6 than that obtained by sequential treatment with a medicinal mushroom Phellinus linteus extract and then LPS. The DC differentiation/maturation activity and the component inducing apoptosis in cancer cells were separable by column chromatography.