Allosuppressor and allohelper T cells in acute and chronic graft-vs.-host disease. II. F1 recipients carrying mutations at H-2K and/or I-A.

By induction of a graft-vs.-host reaction (GVHR) in nonirradiated H-2-different F1 mice, one can induce stimulatory pathological symptoms, such as lymphadenopathy and hypergammaglobulinemia, combined with the production of autoantibodies characteristic of systemic lupus erythematosus (SLE). Alternatively, the GVHR can lead to the suppressive pathological symptoms, such as pancytopenia and hypogammaglobulinemia, characteristic of acute GVH disease (GVHD). Whether stimulatory or suppressive symptoms are induced by a GVHR depends, in our view (2-4), on the functional subset of donor T cells activated in the F1 host. The purpose of the present study was to investigate whether class I and/or class II H-2 alloantigens can selectively trigger, out of a pool of unselected donor T cells, those subpopulations of T cells responsible for the stimulatory and suppressive GVH symptoms, respectively. For the induction of the GVHR, 10(8) lymphoid cells from C57BL/6 (B6) donors were injected into three kinds of F1 hybrid mice, which had been bred from H-2 mutant strains on a B6 background. Whereas the I-A-disparate (B6 X bm12)F1 recipients exclusively developed stimulatory GVH symptoms, including SLE-like autoantibodies and immune complex glomerulonephritis, the K locus-disparate (B6 X bm1)F1 recipients showed neither clearly stimulatory nor clearly suppressive GVH symptoms. In marked contrast, the (bm1 X bm12)F1 recipients, which differ from the B6 donor strain by mutations at both K and I-A locus, initially developed stimulatory GVH symptoms, but rapidly thereafter showed the suppressive pathological symptoms of acute GVHD and died. Moreover, spleen cells obtained from (B6 X bm12)F1 mice injected with B6 donor cells helped the primary anti-sheep erythrocyte (SRBC) response of normal (B6 X bm12)F1 spleen cells in vitro, whereas spleen cells (bm1 X bm12)F1 mice injected with B6 donor cells strongly suppressed the primary anti-SRBC response of normal (bm1 X bm12)F1 spleen cells. Spleen cells from the K locus-disparate (B6 X bm1)F1 recipients also suppressed the primary anti-SRBC of normal (B6 X bm1)F1 spleen cells; this suppression, however, was weak when compared with the suppression induced by spleen cells from GVH (bm1 X bm12)F1 mice. Taken together, these findings indicate that a small class II (I-A) antigenic difference suffices to trigger the alloreactive donor T helper cells causing SLE-like GVHD. In contrast, both class I (H-2K) and class II (I-A) differences are required to trigger the subsets of donor T cells responsible for acute GVHD. It appears that alloreactive donor T helper cells induce the alloreactive T suppressor cells, which then act as the suppressor effector cells causing the pancytopenia of acute GVHD. These findings may help to understand the variability of GVH-like diseases caused by a given etiologic agent, their cellular pathogenesis, and association with certain HLA loc

Josephson Current between Triplet and Singlet Superconductors

The Josephson effect between triplet and singlet superconductors is studied. Josephson current can flow between triplet and singlet superconductors due to the spin-orbit coupling in the spin-triplet superconductor but it is finite only when triplet superconductor has $L_z=-S_z=\pm 1$, where $L_z$ and $S_z$ are the perpendicular components of orbital angular momentum and spin angular momentum of the triplet Cooper pairs, respectively. The recently observed temperature and orientational dependence of the critical current through a Josephson junction between UPt$_3$ and Nb is investigated by considering a non-unitary triplet state.Comment: 4 pages, no figure

Expression of oncoproteins and the amount of eosinophilic and lymphocytic infiltrates can be used as prognostic factors in gastric cancer. Dutch Gastric Cancer Group (DGCG).

Preoperative staging of gastric cancer is difficult. Several molecular markers associated with initiation and progression of cancer seem promising for obtaining preoperative prognostic information. To investigate whether these markers are indicative especially for the presence of lymph node metastases in patients with gastric cancer, we have examined primary tumour specimens from 105 patients with primary adenocarcinoma of the stomach entered in a surgical trial. In this trial, lymph node status was determined by strictly quality-controlled lymph node dissection and examination. The selected markers were growth regulators (p53, Rb and myc), metastasis-suppressor gene product (nm23), adhesion molecules (Ep-CAM, E-cadherin, CD44v5 and CD44v6) and urokinase-type plasminogen activator (u-PA). Also, the amount of eosinophilic and lymphocytic infiltrates available post-operatively was analysed with respect to its prognostic value for lymph node status. Moreover, the association of these parameters with survival and disease-free period (DFP) was evaluated. Of all molecular markers investigated, only Rb expression had a significant association with the presence of lymph node metastasis in both univariate and multivariate analysis. For curative resectability, a significant association was found with Rb and E-cadherin expression, while in multivariate analysis Rb and myc were selected as the combination with additional independent prognostic value, and E-cadherin had no additional independent value. For overall survival in univariate analysis, the amount of both eosinophilic and lymphocytic infiltrates and Rb and myc expression were of significant prognostic value. Only the amount of lymphocytic infiltrate had a prognostic significance for DFP. In stepwise multivariate analysis, TNM stage (I + II) and marked lymphocytic infiltrate were associated with better overall survival and longer DFP. We conclude that, if these results are confirmed in a larger series of patients, molecular markers can provide useful prognostic information

Bistability in the Tunnelling Current through a Ring of NN Coupled Quantum Dots

We study bistability in the electron transport through a ring of N coupled quantum dots with two orbitals in each dot. One orbital is localized (called b orbital) and coupling of the b orbitals in any two dots is negligible; the other is delocalized in the plane of the ring (called d orbital), due to coupling of the d orbitals in the neighboring dots, as described by a tight-binding model. The d orbitals thereby form a band with finite width. The b and d orbitals are connected to the source and drain electrodes with a voltage bias V, allowing the electron tunnelling. Tunnelling current is calculated by using a nonequilibrium Green function method recently developed to treat nanostructures with multiple energy levels. We find a bistable effect in the tunnelling current as a function of bias V, when the size N>50; this effect scales with the size N and becomes sizable at N~100. The temperature effect on bistability is also discussed. In comparison, mean-field treatment tends to overestimate the bistable effect.Comment: Published in JPSJ; minor typos correcte

Higher-Order Results for the Relation between Channel Conductance and the Coulomb Blockade for Two Tunnel-Coupled Quantum Dots

We extend earlier results on the relation between the dimensionless tunneling channel conductance $g$ and the fractional Coulomb blockade peak splitting $f$ for two electrostatically equivalent dots connected by an arbitrary number $N_{\text{ch}}$ of tunneling channels with bandwidths $W$ much larger than the two-dot differential charging energy $U_{2}$. By calculating $f$ through second order in $g$ in the limit of weak coupling ($g \rightarrow 0$), we illuminate the difference in behavior of the large-$N_{\text{ch}}$ and small-$N_{\text{ch}}$ regimes and make more plausible extrapolation to the strong-coupling ($g \rightarrow 1$) limit. For the special case of $N_{\text{ch}}=2$ and strong coupling, we eliminate an apparent ultraviolet divergence and obtain the next leading term of an expansion in $(1-g)$. We show that the results we calculate are independent of such band structure details as the fraction of occupied fermionic single-particle states in the weak-coupling theory and the nature of the cut-off in the bosonized strong-coupling theory. The results agree with calculations for metallic junctions in the $N_{\text{ch}} \rightarrow \infty$ limit and improve the previous good agreement with recent two-channel experiments.Comment: 27 pages, 1 RevTeX file with 4 embedded Postscript figures. Uses eps

Fine structure in the off-resonance conductance of small Coulomb blockade systems

We show how a fine, multiple-peak structure can arise in the off-resonance, zero-bias conductance of Coulomb blockade systems. In order to understand how this effect comes about one must abandon the orthodox, mean-field understanding of the Coulomb blockade phenomenon and consider quantum fluctuations in the occupation of the single-particle electronic levels. We illustrate such an effect with a spinless Anderson-like model for multi-level systems and an equation-of-motion method for calculating Green's functions that combines two simple decoupling schemes.Comment: 5 pages, 3 figures, postscript file also available at http://www.pa.uky.edu/~palacios/papers/eom.ps One figure added. Discussion of results extende

Josephson current in s-wave superconductor / Sr_2RuO_4 junctions

The Josephson current between an s-wave and a spin-triplet superconductor Sr$_2$RuO$_4$ (SRO) is studied theoretically. In spin-singlet / spin-triplet superconductor junctions, there is no Josephson current proportional to $\sin \phi$ in the absence of the spin-flip scattering near junction interfaces, where $\phi$ is a phase-difference across junctions. Thus a dominant term of the Josephson current is proportional to $\sin 2\phi$ . The spin-orbit scattering at the interfaces gives rise to the Josephson current proportional to $\cos\phi$, which is a direct consequence of the chiral paring symmetry in SRO

Dietary Mannan Oligosaccharides Modulate Gut Microbiota, Increase Fecal Bile Acid Excretion, and Decrease Plasma Cholesterol and Atherosclerosis Development

Functional Genomics of Systemic Disorder