Masato Nakamura

Vascular endothelial growth factor (VEGF) mRNA isoform expression pattern is correlated with liver metastasis and poor prognosis in colon cancer.

Vascular endothelial growth factor (VEGF) is a well known factor that induces angiogenesis. Four isoforms, i.e. VEGF206, 189, 165, and 121, have been identified. We examined the isoform patterns of VEGF mRNA using reverse transcription polymerase chain reaction (RT-PCR) analysis in 61 colon cancers. All the colon cancers examined expressed VEGF121. The isoform patterns were classified into three groups: type 1, VEGF121; type 2, VEGF121 + VEGF165; type 3, VEGF121 + VEGF165 + VEGF189. Three of the 61 colon cancers examined showed type 1 expression, 26 showed type 2 expression and 32 showed the type 3 pattern. The patients with liver metastases showed the type 3 isoform expression pattern at a significantly higher incidence (12 of 16, 75%) than those without liver metastasis (20 of 45, 44%) (P=0.036). The type 3 isoform pattern was significantly associated with M1 stage (P=0.019). The patients with colon cancer and the type 3 isoform pattern showed significantly poor prognosis (P < 0.01, Cox-Mantel). The colon cancers with the type 3 pattern showed a significantly higher involvement of veins (P=0.006). These observations suggest that the aberrant type 3 expression pattern of VEGF189 mRNA isoforms is correlated with liver metastasis, M stage, and poor prognosis in colon cancer.

Storm‐substorm relationship: Contribution of the tail current to Dst

The Dst index has been conventionally used as a measure of the storm intensity, which ideally assumes that the associated ground magnetic disturbance is caused by the ring current. The present study examines the contribution of the tail current to Dst, focusing on the occurrence of geosynchronous dipolarization close to the Dst minimum, in other words, the start of the storm recovery phase. The Sym-H (referred to as Dst(Sym-H) hereafter) index rather than the conventional Dst index is used because of its higher time resolution (1 min). For the June 1998 storm event, dipolarization started at two GOES satellites and the Geotail satellite in the near-Earth tail when Dst(Sym-H) reached its minimum. This result indicates that the source current was located outside of geosynchronous orbit, and therefore the recovery of Dst(Sym-H) can be attributed to the reduction of the tail current rather than the decay of the ring current. A statistical study based on 59 storm events (79 GOES events) confirms the tendency for geosynchronous magnetic field to dipolarize at the Dst(Sym-H) minimum. It is therefore highly likely that the Dst(Sym-H) minimum is misidentified as the start of the ring current (storm) decay at a time when the ring current may actually be intensifying owing to substorm-associated injection. From the magnitude of the Dst(Sym-H) recovery during the interval of geosynchronous dipolarization, the contribution of the tail current to Dst(Sym-H) at the Dst(Sym-H) minimum is estimated to be 20–25%. However, the contribution of the tail current may be even larger because the tail current may not return to preintensification levels and may continue to contribute to Dst(Sym-H) after dipolarization. The trigger of dipolarization (substorm) and the subsequent recovery of Dst(Sym-H) tend to take place in the course of the reduction of the southward interplanetary magnetic field (IMF) BZ. It is therefore suggested that the ring current (storm) recovers after the substorm since the magnetospheric convection weakens because of weaker southward IMF BZ.

Thrombospondin 2 expression is correlated with inhibition of angiogenesis and metastasis of colon cancer

SummaryTwo subtypes of thrombospondin (TSP-1 and TSP-2) have inhibitory roles in angiogenesis in vitro, although the biological significance of these TSP isoforms has not been determined in vivo. We examined TSP-1 and TSP-2 gene expression by reverse transcription polymerase chain reaction (RT-PCR) analysis in 61 colon cancers. Thirty-eight of these 61 colon cancers were positive for TSP-2 expression and showed hepatic metastasis at a significantly lower incidence than those without TSP-2 expression (P = 0.02). TSP-2 expression was significantly associated with M0 stage in these colon cancers (P = 0.03), whereas TSP-1 expression showed no apparent correlation with these factors. The colon cancer patients with TSP-2 expression showed a significantly low frequency of liver metastasis correlated with the cell-associated isoform of vascular endothelial growth factor (VEGF-189) (P = 0.0006). Vascularity was estimated by CD34 staining, and TSP-2(–)/VEGF-189(+) colon cancers showed significantly increased vessel counts and density in the stroma (P < 0.0001). TSP-2(–)/VEGF-189(+) colon cancer patients also showed significantly poorer prognosis compared with those with TSP-2(+) / VEGF-189(–) (P = 0.0014). These results suggest that colon cancer metastasis is critically determined by angiogenesis resulting from the balance between the angioinhibitory factor TSP-2 and angiogenic factor VEGF-189.

Geotail observations of substorm onset in the inner magnetotail

On April 26, 1995, while Geotail was in the near-equatorial magnetotail at 13 RE and 2300 LT, a substorm onset occurred that was documented by ground magnetograms, auroral kilometric radiation, and magnetic field and particle data from four spacecraft at and near geosynchronous orbit. Although Geotail was initially outside a greatly thinned current sheet, plasma sheet thickening associated with the substorm dipolarization quickly caused Geotail to move into the plasma sheet where it observed field-aligned earthward moving ions with velocities of 400 km/s. During the subsequent few minutes as the magnetic field became more northward, the velocities increased with particles moving increasingly into the energy range of the energetic particle experiment. These flows culminated with 1-min worth of earthward flow of 2000 km/s that was perpendicular to the northward B field. Such flow, probably the largest ever detected at 13 RE, was confirmed by the observation of an intense dc electric field of 50 mV/m (0.3 megavolts/RE). This large field is probably inductive, caused by reconnection that occurred tailward of the spacecraft, and related to the acceleration processes associated with particle injection at geosynchronous orbit. Energy and magnetic flux conservation arguments suggest that this rapid flow has a small cross-tail dimension of the order of 1 RE. The data appear to support a simulation of Birn and Hesse [1996] which showed rapid earthward flows from a reconnection line at 23 RE that caused a tailward expansion of a region of dipolarized flux. Subsequent to the onset, Geotail observed plasma vortices with typical velocities of 50–100 km/s that occurred in a high-beta plasma sheet with a 15-nT northward magnetic field. The vortices were punctuated by occasional flow bursts with velocities up to 400 km/s, one of which was accompanied by a violently varying magnetic field where north/south field components were as large as 30 nT and as small as −8 nT.

Substorm onset timing: The December 31, 1995, event

The objective of the present study is to examine the timing of various onset-associated signatures and address the cause-and-effect relationship between the formation of a near-Earth neutral line (NENL) and the trigger of tail current disruption. An event selected for this study took place on December 31, 1995. In this event the Geotail satellite was located at X = −30.3 RE in the midnight sector at a local time between the GOES 8 and 9 geosynchronous satellites. The timing of the Geotail observation of a fast (950-km/s) tailward convection flow accompanied with southward Bz (< −10 nT) indicates that the near-Earth reconnection process started at least 4 min before the ground substorm onset, which was identified by various signatures such as an auroral expansion, a Pi2 onset, a positive bay onset, and a negative bay onset. Both GOES satellites observed dipolarization. GOES 9 was located closer to the onset meridian and observed a sudden recovery (dipolarization) of the local magnetic field but with a noticeable (≈1 min) delay from the ground onset. This delay can be interpreted in terms of the earthward expansion of tail current disruption initiated outside of geosynchronous orbit. The timing of all these features is consistent with the idea that dipolarization is a pileup of magnetic flux conveyed from the NENL. However, a sharp decrease in the H component at GOES 9 prior to the local dipolarization onset and the sudden start of a substorm are difficult to explain in terms of this idea. It is asserted that tail current disruption is a unique process rather than a direct consequence of the NENL formation, although it is possible that the reconnection process sets up a favorable condition for triggering tail current disruption. The fast plasma flow in the plasma sheet ceased soon after the substorm onset, suggesting that during the expansion phase, the tail current disruption took over the near-Earth reconnection process as a major role in the substorm dynamics.

Electrophoretic mobility of colloidal particles coated with a layer of adsorbed polymers

A general expression is given for the electrophoretic mobility of a large charged colloidal particle coated with a layer of adsorbed charged polymers. A liquid flow within the polymer layer is taken into account. The potential distribution is calculated on the basis of the non-linear Poisson Boltzmann equation. Simple approximate analytic expressions for the electrophoretic mobility are derived for various cases.

Adenovirus-mediated anti-K-ras ribozyme induces apoptosis and growth suppression of human pancreatic carcinoma.

Human pancreatic cancer is a lethal malignancy, and the lesions show a very high incidence of point mutations of the K-ras oncogene. These alterations can be used as potential targets for specific ribozyme (Rz)-mediated growth suppression of the cancer cells. We designed an anti-K-ras Rz against mutant K-ras gene transcripts (codon 12, GGT to GTT) and generated a recombinant adenovirus (rAd) to express the Rz (rAd/anti-K-ras Rz). More than 95% of Capan-1 human pancreatic cells were infected with rAd/anti-K-ras Rz when treated with the virus at 200 plaque-forming units/cell. The virus, rAd/anti-K-ras Rz, significantly suppressed mutant K-ras gene expression and inhibited the growth of Capan-1 cells. At 3 days postinfection, we observed maximum growth suppression of the cells, characteristic morphological changes of apoptosis such as nuclear condensation and oligonucleosomal DNA fragmentation, and suppression of bcl-2 oncoprotein. These changes were not found in control virus-infected cells. Our results indicated that the virus rAd/anti-K-ras Rz specifically down-regulated the K-ras/bcl-2 pathway and induced apoptotic changes in Capan-1 pancreatic carcinoma cells. High-efficiency adenovirus-mediated delivery of anti-K-ras Rz could become a significant gene therapy strategy against human pancreatic cancer.

Acceleration and heating of cold ion beams in the plasma sheet boundary layer observed with GEOTAIL

The GEOTAIL/Low Energy Particle (LEP) observations have revealed detailed features of acceleration and heating of cold ion beams in the plasma sheet boundary layer (PSBL). In the lobe region, the cold ion beams are flowing tailward nearly along magnetic field lines with small perpendicular drift toward the plasma sheet. Upon entering the plasma sheet, these cold ion beams are heated and accelerated up to several keV/q in the PSBL where a high-speed ion flow is observed separately and simultaneously, and finally assimilated into the hot component of the plasma sheet proper. It should be noted that the acceleration of the cold ion beams in the PSBL is observed in the direction perpendicular to the magnetic field, and the perpendicular velocities of the cold ion beams during the acceleration coincide well with those of the high-speed ion beams. This fact suggests that the perpendicular acceleration is due to an increase of the E×B drift speed in the PSBL as particles move from the lobe to the central plasma sheet. The electric field intensity for the observed E×B drift motion is estimated as 2–5 mV/m. The direction of the electric field inferred from the ion motion in the PSBL is mainly in the south-to-north direction rather than the dawn-to-dusk direction which is generally thought to be typical in the tail lobe. The direction of the acceleration is at times observed to change drastically, which suggests that the electric field direction fluctuates significantly as well.

Neutron and proton energy spectra from the non-mesonic weak decays of HeΛ5 and CΛ12

We have simultaneously measured the energy spectra of neutrons and protons emitted in the non-mesonic weak decays of 5_Lambda-He and 12_Lambda-C hypernuclei produced via the (pi^+,k^+) reaction with much higher statistics over those of previous experiments. The neutron-to-proton yield ratios for both hypernuclei at a high energy threshold (60 MeV) were approximately equal to two, which suggests that the ratio of the neutron- and proton-induced decay channels, Gn(Lambda n ->nn)/Gp(Lambda p ->np), is about 0.5. In the neutron energy spectra, we found that the yield of the low-energy component is unexpectedly large, even for 5_Lambda-He.

Magnetopause characteristics during a four-hour interval of multiple crossings observed with GEOTAIL

This paper presents multiple magnetopause crossings observed with Geotail on October 17, 1992. On this day Geotail skimmed the magnetopause in the dawn flank sector (the spacecraft had a speed of ∼0.7 km/s normal to the nominal magnetopause) and crossed the magnetopause more than 45 times in four hours. When the magnetopause crossings were observed, the interplanetary magnetic field was southerly directed. For the large number of crossings we have examined the magnetopause normal directions by using the minimum variance analysis technique, and as a result we have confirmed in a statistical sense a clear inbound/outbound dependence of the magnetopause orientation consistent with the tailward-moving recurrent bumps in the magnetopause. In addition, there is an implication that the northward (southward) flow along the magnetopause occured for the inward (outward) directed magnetic field component normal to the magnetopause.