Observation of a multimode plasma response and its relationship to density pumpout and edge-localized mode suppression.

Density pumpout and edge-localized mode (ELM) suppression by applied n=2 magnetic fields in low-collisionality DIII-D plasmas are shown to be correlated with the magnitude of the plasma response driven on the high-field side (HFS) of the magnetic axis but not the low-field side (LFS) midplane. These distinct responses are a direct measurement of a multimodal magnetic plasma response, with each structure preferentially excited by a different n=2 applied spectrum and preferentially detected on the LFS or HFS. Ideal and resistive magneto-hydrodynamic (MHD) calculations find that the LFS measurement is primarily sensitive to the excitation of stable kink modes, while the HFS measurement is primarily sensitive to resonant currents (whether fully shielding or partially penetrated). The resonant currents are themselves strongly modified by kink excitation, with the optimal applied field pitch for pumpout and ELM suppression significantly differing from equilibrium field alignment.

Pedestal bifurcation and resonant field penetration at the threshold of edge-localized mode suppression in the DIII-D Tokamak.

Rapid bifurcations in the plasma response to slowly varying n=2 magnetic fields are observed as the plasma transitions into and out of edge-localized mode (ELM) suppression. The rapid transition to ELM suppression is characterized by an increase in the toroidal rotation and a reduction in the electron pressure gradient at the top of the pedestal that reduces the perpendicular electron flow there to near zero. These events occur simultaneously with an increase in the inner-wall magnetic response. These observations are consistent with strong resonant field penetration of n=2 fields at the onset of ELM suppression, based on extended MHD simulations using measured plasma profiles. Spontaneous transitions into (and out of) ELM suppression with a static applied n=2 field indicate competing mechanisms of screening and penetration of resonant fields near threshold conditions. Magnetic measurements reveal evidence for the unlocking and rotation of tearinglike structures as the plasma transitions out of ELM suppression.

Tokamak operation with safety factor q95 < 2 via control of MHD stability.

Magnetic feedback control of the resistive-wall mode has enabled the DIII-D tokamak to access stable operation at safety factor q(95) = 1.9 in divertor plasmas for 150 instability growth times. Magnetohydrodynamic stability sets a hard, disruptive limit on the minimum edge safety factor achievable in a tokamak, or on the maximum plasma current at a given toroidal magnetic field. In tokamaks with a divertor, the limit occurs at q(95) = 2, as confirmed in DIII-D. Since the energy confinement time scales linearly with current, this also bounds the performance of a fusion reactor. DIII-D has overcome this limit, opening a whole new high-current regime not accessible before. This result brings significant possible benefits in terms of fusion performance, but it also extends resistive-wall mode physics and its control to conditions never explored before. In present experiments, the q(95) < 2 operation is eventually halted by voltage limits reached in the feedback power supplies, not by intrinsic physics issues. Improvements to power supplies and to control algorithms have the potential to further extend this regime.

Evidence for the importance of trapped particle resonances for resistive wall mode stability in high beta tokamak plasmas.

Active measurements of the plasma stability in tokamak plasmas reveal the importance of kinetic resonances for resistive wall mode stability. The rotation dependence of the magnetic plasma response to externally applied quasistatic n=1 magnetic fields clearly shows the signatures of an interaction between the resistive wall mode and the precession and bounce motions of trapped thermal ions, as predicted by a perturbative model of plasma stability including kinetic effects. The identification of the stabilization mechanism is an essential step towards quantitative predictions for the prospects of "passive" resistive wall mode stabilization, i.e., without the use of an "active" feedback system, in fusion-alpha heated plasmas.

The effect of Bacillus subtilis mouth rinsing in patients with periodontitis.

Bacillus subtilis is an effective probiotic product for prevention of enteric infections both in humans and animals. We hypothesized that a mouth rinse containing Bacillus subtilis should adhere to and colonize part of the oral bacteria on periodontal tissue. The rinsing ability of Extraction 300E (containing Bacillus subtilis: E-300) was compared with that of a mouth wash liquid , Neosteline Green (benzethonium chloride; NG) that is commonly used in Japan. Compared with NG rinsing, E-300 rinsing resulted in a marked change in the BANA-score. The mean BANA values (score +/- SD) over the course of the study from 0 to 30 days were 1.52 +/- 0.51 (p < or = 0.1) and 0.30 +/- 0.47 (p < or = 0.01) for E-300, and 1.56 +/- 0.51 and 0.93 +/- 0.68 for NG, respectively. Gingival Index also had improvement, while probing pocket depth and bleeding on probing showed small improvements. Mouth rinsing with E-300 significantly reduced periodontal pathogens compared with NG. These results suggest that Bacillus subtilis is an appropriate mouth rinse for patients with periodontitis.

Reduced critical rotation for resistive-wall mode stabilization in a near-axisymmetric configuration.

Recent DIII-D experiments with reduced neutral beam torque and minimum nonaxisymmetric perturbations of the magnetic field show a significant reduction of the toroidal plasma rotation required for the stabilization of the resistive-wall mode (RWM) below the threshold values observed in experiments that apply nonaxisymmetric magnetic fields to slow the plasma rotation. A toroidal rotation frequency of less than 10 krad/s at the q=2 surface (measured with charge exchange recombination spectroscopy using C VI) corresponding to 0.3% of the inverse of the toroidal Alfvén time is sufficient to sustain the plasma pressure above the ideal MHD no-wall stability limit. The low-rotation threshold is found to be consistent with predictions by a kinetic model of RWM damping.

Measurement of the resistive-wall-mode stability in a rotating plasma using active MHD spectroscopy.

The stability of the resistive-wall mode (RWM) in DIII-D plasmas above the conventional pressure limit, where toroidal plasma rotation in the order of a few percent of the Alfve n velocity is sufficient to stabilize the n=1 RWM, has been probed using the technique of active MHD spectroscopy at frequencies of a few Hertz. The measured frequency spectrum of the plasma response to externally applied rotating resonant magnetic fields is well described by a single-mode approach and provides an absolute measurement of the damping rate and the natural mode rotation frequency of the stable RWM.

Sustained stabilization of the resistive-wall mode by plasma rotation in the DIII-D tokamak.

Values of the normalized plasma pressure up to twice the free-boundary stability limit predicted by ideal magnetohydrodynamic (MHD) theory have been sustained in the DIII-D tokamak. Long-wavelength modes are stabilized by the resistive wall and rapid plasma toroidal rotation. High rotation speed is maintained by minimization of nonaxisymmetric magnetic fields, overcoming a long-standing impediment [E. J. Strait, Phys. Rev. Lett. 74, 2483 (1995)]]. The ideal-MHD pressure limit calculated with an ideal wall is observed as the operational limit to the normalized plasma pressure.

Infiltration of peroxidase-producing eosinophils into the lamina propria of patients with ulcerative colitis.

Little information is available to explain the pathogenesis of ulcerative colitis (UC). In this study, we focused on eosinophils in the lamina propria of the mucosa of patients with UC in the active phase. Biopsy specimens were taken from 17 patients with UC in the active phase, 17 in the inactive phase, and 20 control patients, and submitted for histochemical staining for peroxidase and chloroacetate esterase for microscopic examination. Both peroxidase-producing and chloroacetate esterase-producing cells in the lamina propria increased markedly in the active phase (8.3 +/- 3.1/0.01 mm2 and 6.6 +/- 2.7/0.01 mm2, respectively), compared with values in the inactive phase (0.8 +/- 0.6/0.01 mm2 and 1.3 +/- 0.6/0.01 mm2) or in the controls (1.3 +/- 0.8/0.01 mm2 and 1.3 +/- 0.4/0.01 mm2). Triple staining for peroxidase, chloroacetate esterase, and nonspecific esterase in the specimens revealed that the peroxidase-producing cells constituted a different population from that of neutrophils, macrophages/monocytes, or basophils. A monoclonal antibody specific for eosinophil peroxidase stained almost all infiltrated peroxidase-producing cells. These results indicated that eosinophils with strong peroxidase activity had infiltrated the lamina propria in UC, suggesting an allergic background and the involvement of released peroxidase in the mucosal damage characteristic of UC.

Podofilox-induced regression of Shope papillomas may be independent of host immunity.

We tested the hypothesis that infiltrating leukocytes might contribute to papilloma destruction following podofilox treatment. New Zealand White (NZW) rabbits were inoculated with cottontail rabbit papillomavirus (CRPV) onto abraded areas of the dorsal skin. At 21 d after viral inoculation, 5.0% podofilox solution was applied to some papillomas, whereas others were used as controls. Three rabbits were sacrificed at each of three different periods after treatment initiation (1, 4, and 7 d). Four monoclonal antibodies (MoAbs), RG-16 (for B cells), L11/135 (specific for T cells), 2C4 (specific for class II antigen), and Ki67 (specific for proliferating cells), were used in an immunohistochemical study. All positive cells and total cells in the field were counted with an ocular grid. After 1 d of treatment, proliferation of papilloma cells was strongly suppressed in treated papillomas, but leukocytic infiltration was not altered. At 4 d and 7 d of treatment, there were substantial increases (about two to three times) in the numbers of B and T cells and class II-expressing leukocytes. The upper layers of the papillomas were highly necrotic and cell proliferation was absent in all layers. These data support the view that podofilox has a direct toxic effect on papilloma tissue. Leukocyte infiltration is not strongly associated with papilloma tissue and may not contribute to papilloma destruction.

Eradication of metastatic tumour cells from lymph nodes by local administration of anti-CD3 antibody.

The possibility of in vivo removal of metastatic tumour cells from lymph nodes by local intradermal administration of an anti-CD3 monoclonal antibody (mAb) was examined. Murine tumour cells in the lymph nodes were completely eradicated by intradermal injections of the mAb. This treatment was effective for removal of Lewis lung cancer cells from lymph nodes, but not for removal of subcutaneous tumours of this cell line. This treatment induced in vivo cytotoxicity in the regional lymph nodes against the syngeneic tumour cells. The following in vitro studies suggested that the cytotoxicity was probably mediated mainly by CD4+ T cells, with slight participation of CD8+ T cells. Normal lymph node and spleen cells showed cytotoxicity after in vitro incubation with the mAb for 2 days. Cell sorting with a fluorescein-activated cell sorter showed that CD4+ T cells developed during the incubation to lyse syngeneic tumor cells directly by themselves, macrophages not being involved in this tumour cell lysis. The lytic activity was detected in the cellular fractions, but not in the culture supernatants of these T cells. Furthermore, it was completely blocked by specific antiserum for tumour necrosis factor-alpha (TNF alpha). An immunoprecipitation study revealed that these T cells expressed TNF alpha molecules of 26 kDa, but not of 17 kDa, suggesting that tumour cell lysis was caused by membrane-integrated integrated TNF alpha molecules. These results strongly suggest that local administration of anti-CD3 antibody is a very effective and appropriate procedure for eradication of metastatic tumour cells from regional lymph nodes.

Shope papilloma cell and leukocyte proliferation in regressing and progressing lesions.

Lesions generated by infection with cottontail rabbit papillomavirus frequently undergo spontaneous regression. The purpose of this immunohistochemical study was to compare leukocyte and papilloma cell proliferation in progressing and regressing papillomas and to test the hypothesis that regression was associated with an inhibition of papilloma cell proliferation. The monoclonal antibodies (MAbs) MAb-019 (specific for DNA/bromodeoxyuridine [BrdU] complexes), Ki-67 (specific for actively proliferating cells), L11/135 (specific for rabbit T cells), and 2C4 (specific for rabbit class II antigen) were used for this purpose. In progressing papillomas, there were few leukocytes (< 1%) in the dermis that stained with MAb-019 and Ki-67, whereas these antibodies stained 4.5% and 6.8% of the intraepidermal leukocytes, respectively. Regressing papillomas contained conspicuous leukocytic infiltrates in the dermis, of which 76.9% were L11/135-positive T cells. However, few intradermal leukocytes (< 3%) stained positively with MAb-019 and Ki-67 MAbs, despite expressing rabbit class II antigen. The epidermis of regressing papillomas contained a higher percentage of MAb-019- and Ki-67-positive leukocytes than the epidermis of progressing papillomas. Intraepidermal leukocytes in progressing and regressing papillomas consisted mainly of T cells stained by L11/135. It appeared that many dermal leukocytes (mainly T cells) form a non-cycling T cell population in both progressing and regressing papillomas, whereas intraepidermal T cells in regressing papillomas were effectively activated and represented a cycling T cell population. MAb-019 and Ki-67 MAbs demonstrated similar staining patterns in papilloma and normal tissues. However, in both progressing and regressing papillomas, the Ki-67 MAb usually stained a larger percentage of cells than the MAb-019 MAb. MAb-019 and Ki-67 MAbs showed a homogeneous distribution of positive cells from basal layer to the upper layer in progressing papillomas. On the other hand, in regressing papillomas, cell staining with the two antibodies was concentrated in the basal and lower layers, but not in the upper layers. This result indicates that cell proliferation in the upper epidermal layers is suppressed in regressing papillomas. Our present data show that intraepidermal T- cell activation and suppression of tumor proliferation might play a crucial role in papilloma regression.

Morphometric analysis and identification of infiltrating leucocytes in regressing and progressing Shope rabbit papillomas.

Spontaneous regressions of papillomavirus lesions frequently occur in both human and animal infections. The mechanism by which this occurs is currently unknown. Mononuclear infiltrates are found in regressing human and rabbit papillomas. To assess the potential functional role of these infiltrates in regression, we have characterized and quantitated the cell types present in regressing rabbit lesions. Forty New Zealand white rabbits were inoculated with cottontail rabbit papillomavirus (CRPV) at 2 sites on the dorsal skin. All tumors on 6 rabbits markedly decreased in volume within 6 to 8 weeks of inoculation. Tumors on 4 of these 6 regressor rabbits were studied by immunohistochemistry. Regressor papillomas had conspicuous leucocytic infiltrates, most concentrated at the epithelial basement membrane, and often obliterating the basal cells of the germinal layer. Infiltrating leucocytes were also concentrated in the subjacent dermis immediately beneath the basement membrane. The infiltrates gradually lessened at increased depths in the dermis. In contrast, progressor papillomas contained fewer leucocytes, which were randomly distributed in the dermis. The phenotype of the infiltrating leucocytes was examined in 4 regressing and 12 progressing papillomas. In regressing papillomas, infiltrating leucocytes were predominantly T cells (68.0%), with relatively few B cells (7.4%). Progressing papilloma dermis contained fewer T cells and B cells than regressing papillomas. Most of the infiltrating T cells in regressing papillomas were labelled with a rabbit MHC-class-II-specific monoclonal antibody (MAb) (2C4), in contrast to only a small number in progressing papillomas. In addition to the leucocytic infiltrates, keratinocytes in regressing, but not in progressing, papillomas, frequently exhibited strong 2C4 staining. These results demonstrate that infiltration with T cells expressing rabbit class II is characteristic of regressing Shope papillomas and strengthens the assertion that cell-mediated immunity is the mechanism of Shope papilloma regression.

Expression of human immunodeficiency virus type 1 (HIV-1) gag antigens on the surface of a cell line persistently infected with HIV-1 that highly expresses HIV-1 antigens.

MT-4 cells persistently infected with human immunodeficiency virus type 1 (HIV-1) (MT-4/HIV-1) were recently isolated (K. Ikuta, C. Morita, M. Nakai, N. Yamamoto, and S. Kato, Japan. J. Cancer Res. (Gann), 79, 418-423, 1988). Mouse hybridoma cell clones producing monoclonal antibodies (MoAbs) to HIV-1 gag p24 and p18, and pol reverse transcriptase (RT) were isolated by using this MT-4/HIV-1 cell line for the screening of MoAb production by the immunofluorescence (IF) test. By indirect IF tests of acetone-fixed cells with these MoAbs, the IF intensities in MT-4/HIV-1 cells were found to be higher than those in the other HIV-1 infected cells, such as MOLT-4/HIV-1, HL-60/HIV-1, and U937/HIV-1 cells. Cell surface expression of the HIV-1 gag p24 and p18 antigens examined by IF and radioimmune techniques with these MoAbs revealed the p24 and p18 antigens to be expressed strongly on the cell surface of MT-4/HIV-1 cells and faintly on the cell surface of MOLT-4/HIV-1 cells, respectively. However, monoclonal antibody isolated in the present study failed to detect pol RT antigen on the surface of MT-4/HIV-1 cells. These results indicate that the gag p24 and p18 antigens are expressed, at least in part, on the surface of HIV-1-infected cells.

Antitumor efficacy of two kinds of tumor vaccine modified with vaccinia virus.

We compared antitumor effectiveness of two types of tumor vaccine modified with vaccinia virus (VV). One type is UV-inactivated VV (UV-VV) -absorbed tumor cell vaccine (UV-VV TCV) produced by tumor cells that had been absorbed in vitro with UV-VV and subsequently X-irradiated with 10(4) rads. The other type is vaccinia oncolysate vaccine (VOV) from tumor cells that had been infected in vitro with live VV and subsequently sonicated. C3H/HeN mice were inoculated i.p. with UV-VV after whole body X-irradiation with 150 rads. After 3 weeks, the two kinds of vaccine were administered i.p. 3 times at weekly intervals. One week after the last injection, mice were challenged i.p. with syngeneic MH134 or X5563 viable tumor cells at different doses. The fifty percent tumor lethal doses (TLD50) of MH134 in mice treated with UV-VV TCV and VOV were 10(6.6) and 10(5.3), respectively, whereas the TLD50 of MH134 in non-treated mice was 10(0.6). The TLD50 of X5563 in mice treated with UV-VV TCV and VOV were 10(6.5) and 10(4.4), respectively, while the TLD50 of X5563 in non-treated mice was 10(0.5). These results show that UV-VV TCV is more effective than VOV. We suggest that the complete cell structure of the vaccine is more effective for enhancing tumor immunity.

Effect of a histamine H2-receptor antagonist, famotidine, on gastric secretion in healthy subjects.

The effects of 20 mg of famotidine or placebo on secretion of gastric juice and gastric acid were studied in ten healthy subjects in a randomized, crossover study. Gastric juice was aspirated and collected at hourly intervals for 24 hours after oral administration, and acid output was calculated based on gastric juice output and acid concentration. Secretion of gastric juice and acid output were lower after famotidine was administered than after placebo; over the 12-hour post-administration period, the hourly acid concentrations were significantly lower after famotidine than after placebo. During the 12 hours after famotidine or placebo, gastric juice output was 180.7 +/- 32.1 ml (mean +/- SE) in the placebo group and 64.7 +/- 9.1 ml in the famotidine group (P less than 0.01); acid concentrations were 49.3 +/- 3.8 mmol/L in the placebo group and 9.6 +/- 3.1 mmol/L in the famotidine group (P less than 0.01); acid output was 8.89 +/- 1.59 mmol in the placebo group and 0.55 +/- 0.17 mmol in the famotidine group (P less than 0.01). These results support the effectiveness of a 12 hour or possibly a 24-hour dosing interval for famotidine.