Misdiagnosis of hereditary amyloidosis as AL (Primary) amyloidosis

Background: Hereditary, autosomal dominant amyloidosis, caused by mutations in the genes encoding transthyretin, fibrinogen A -chain, lysozyme, or apolipoprotein A-I, is thought to be extremely rare and is not routinely included in the differential diagnosis of systemic amyloidosis unless there is a family history. Methods: We studied 350 patients with systemic amyloidosis, in whom a diagnosis of the light-chain (AL) type of the disorder had been suggested by clinical and laboratory findings and by the absence of a family history, to assess whether they had amyloidogenic mutations. Results: Amyloidogenic mutations were present in 34 of the 350 patients (9.7 percent), most often in the genes encoding fibrinogen A -chain (18 patients) and transthyretin (13 patients). In all 34 of these patients, the diagnosis of hereditary amyloidosis was confirmed by additional investigations. A low-grade monoclonal gammopathy was detected in 8 of the 34 patients (24 percent). Conclusions: A genetic cause should be sought in all patients with amyloidosis that is not the reactive systemic amyloid A type and in whom confirmation of the AL type cannot be obtained

Effect of annealing on glassy dynamics and non-Fermi liquid behavior in UCu_4Pd

Longitudinal-field muon spin relaxation (LF-muSR) experiments have been performed in unannealed and annealed samples of the heavy-fermion compound UCu_4Pd to study the effect of disorder on non-Fermi liquid behavior in this material. The muon spin relaxation functions G(t,H) obey the time-field scaling relation G(t,H) = G(t/H^gamma) previously observed in this compound. The observed scaling exponent gamma = 0.3 pm 0.1, independent of annealing. Fits of the stretched-exponential relaxation function G(t) = exp[-(Lambda t)^K] to the data yielded stretching exponentials K < 1 for all samples. Annealed samples exhibited a reduction of the relaxation rate at low temperatures, indicating that annealing shifts fluctuation noise power to higher frequencies. There was no tendency of the inhomogeneous spread in rates to decrease with annealing, which modifies but does not eliminate the glassy spin dynamics reported previously in this compound. The correlation with residual resistivity previously observed for a number of NFL heavy-electron materials is also found in the present work.Comment: 4 pages, 3 figures, submitted to 10th International Conference on Muon Spin Rotation, Relaxation, and Resonance, Oxford, UK, August 200

Quenched Chiral Perturbation Theory for Heavy-light Mesons

We formulate quenched chiral perturbation theory for heavy-light mesons coupled to pions, and calculate the one-loop chiral logarithmic corrections to $f_B$, $f_{B_{s}}$, $B_B$ and $B_{B_{s}}$. We also calculate these corrections for ``partially quenched'' theories. In both theories, the chiral logarithms diverge in the chiral limit, indicating that (partially) quenched theories should not be used to study this limit. Comparing the chiral logarithms to those in QCD, we estimate the errors caused by (partial) quenching. By forming suitable ratios, we can reduce the uncertainties in our estimates.Comment: 22 pages, revtex format, 5 Postscript figure

Implications of the Top Quark Mass Measurement for the CKM Parameters, xsx_s and CP Asymmetries

Motivated by the recent determination of the top quark mass by the CDF collaboration, \mt =174 \pm 10 ^{+13}_{-12} GeV, we review and update the constraints on the parameters of the quark flavour mixing matrix $V_{CKM}$ in the standard model. In performing our fits, we use inputs from the measurements of the following quantities: (i) \abseps, the CP-violating parameter in $K$ decays, (ii) \delmd, the mass difference due to the \bdbdbar\ mixing, (iii) the matrix elements \absvcb and \absvub, and (iv) $B$-hadron lifetimes. We find that the allowed region of the unitarity triangle is very large, mostly due to theoretical uncertainties. (This emphasizes the importance of measurements of CP-violating rate asymmetries in the $B$ system.) Nevertheless, the present data do somewhat restrict the allowed values of the coupling constant product $f_{B_d}\sqrt{\hat{B}_{B_d}}$ and the renormalization-scale invariant bag constant $\hat{B}_K$. With the updated CKM matrix we present the currently-allowed range of the ratio $\vert V_{td}/V_{ts} \vert$, as well as the standard model predictions for the \bsbsbar\ mixing parameter \xs and the quantities $\sin 2\alpha$, $\sin 2\beta$ and $\sin^2\gamma$, which characterize the CP-asymmetries in $B$-decays. The ALEPH collaboration has recently reported a significant improvement on the lower limit on the \bs-\bsb mass difference, $\Delta M_s/\Delta M_d > 11.3$ (95\% C.L.). This has interesting consequences for the CKM parameters which are also worked out. NOTE: this is a revised and updated version of our previous paper.Comment: LaTeX, 27 pages, 16 uuencoded figures (enclosed), CERN-TH.7398/94, UdeM-GPP-TH-94-0

Human Salmonella Typhi exposure generates differential multifunctional cross‐reactive T‐cell memory responses against Salmonella Paratyphi and invasive nontyphoidal Salmonella

Objective There are no vaccines for most of the major invasive Salmonella strains causing severe infection in humans. We evaluated the specificity of adaptive T memory cell responses generated after Salmonella Typhi exposure in humans against other major invasive Salmonella strains sharing capacity for dissemination. Methods T memory cells from eleven volunteers who underwent controlled oral challenge with wt S. Typhi were characterised by flow cytometry for cross‐reactive cellular cytokine/chemokine effector responses or evidence of degranulation upon stimulation with autologous B‐lymphoblastoid cells infected with either S. Typhi, Salmonella Paratyphi A (PA), S. Paratyphi B (PB) or an invasive nontyphoidal Salmonella strain of the S. Typhimurium serovar (iNTSTy). Results Blood T‐cell effector memory (TEM) responses after exposure to S. Typhi in humans evolve late, peaking weeks after infection in most volunteers. Induced multifunctional CD4+ Th1 and CD8+ TEM cells elicited after S. Typhi challenge were cross‐reactive with PA, PB and iNTSTy. The magnitude of multifunctional CD4+ TEM cell responses to S. Typhi correlated with induction of cross‐reactive multifunctional CD8+ TEM cells against PA, PB and iNTSTy. Highly multifunctional subsets and T central memory and T effector memory cells that re‐express CD45 (TEMRA) demonstrated less heterologous T‐cell cross‐reactivity, and multifunctional Th17 elicited after S. Typhi challenge was not cross‐reactive against other invasive Salmonella. Conclusion Gaps in cross‐reactive immune effector functions in human T‐cell memory compartments were highly dependent on invasive Salmonella strain, underscoring the importance of strain‐dependent vaccination in the design of T‐cell‐based vaccines for invasive Salmonella

Critical scaling of the a.c. conductivity for a superconductor above Tc

We consider the effects of critical superconducting fluctuations on the scaling of the linear a.c. conductivity, \sigma(\omega), of a bulk superconductor slightly above Tc in zero applied magnetic field. The dynamic renormalization- group method is applied to the relaxational time-dependent Ginzburg-Landau model of superconductivity, with \sigma(\omega) calculated via the Kubo formula to O(\epsilon^{2}) in the \epsilon = 4 - d expansion. The critical dynamics are governed by the relaxational XY-model renormalization-group fixed point. The scaling hypothesis \sigma(\omega) \sim \xi^{2-d+z} S(\omega \xi^{z}) proposed by Fisher, Fisher and Huse is explicitly verified, with the dynamic exponent z \approx 2.015, the value expected for the d=3 relaxational XY-model. The universal scaling function S(y) is computed and shown to deviate only slightly from its Gaussian form, calculated earlier. The present theory is compared with experimental measurements of the a.c. conductivity of YBCO near Tc, and the implications of this theory for such experiments is discussed.Comment: 16 pages, submitted to Phys. Rev.

On the effects of the magnetic field and the isotopic substitution upon the infrared absorption of manganites

Employing a variational approach that takes into account electron-phonon and magnetic interactions in $La_{1-x}A_xMnO_3$ perovskites with $0<x<0.5$, the effects of the magnetic field and the oxygen isotope substitution on the phase diagram, the electron-phonon correlation function and the infrared absorption at $x=0.3$ are studied. The lattice displacements show a strong correlation with the conductivity and the magnetic properties of the system. Then the conductivity spectra are characterized by a marked sensitivity to the external parameters near the phase boundary.Comment: 10 figure

B-->pi and B-->K transitions in standard and quenched chiral perturbation theory

We study the effects of chiral logs on the heavy-->light pseudoscalar meson transition form factors by using standard and quenched chiral perturbation theory combined with the static heavy quark limit. The resulting expressions are used to indicate the size of uncertainties due to the use of the quenched approximation in the current lattice studies. They may also be used to assess the size of systematic uncertainties induced by missing chiral log terms in extrapolating toward the physical pion mass. We also provide the coefficient multiplying the quenched chiral log, which may be useful if the quenched lattice studies are performed with very light mesons.Comment: 33 pages, 8 PostScript figures, version to appear in PR

Role of circulating T follicular helper subsets following Ty21a immunization and oral challenge with wild type S. Typhi in humans

Despite decades of intense research, our understanding of the correlates of protection against Salmonella Typhi (S. Typhi) infection and disease remains incomplete. T follicular helper cells (TFH), an important link between cellular and humoral immunity, play an important role in the development and production of high affinity antibodies. While traditional TFH cells reside in germinal centers, circulating TFH (cTFH) (a memory subset of TFH) are present in blood. We used specimens from a typhoid controlled human infection model whereby participants were immunized with Ty21a live attenuated S. Typhi vaccine and then challenged with virulent S. Typhi. Some participants developed typhoid disease (TD) and some did not (NoTD), which allowed us to assess the association of cTFH subsets in the development and prevention of typhoid disease. Of note, the frequencies of cTFH were higher in NoTD than in TD participants, particularly 7 days after challenge. Furthermore, the frequencies of cTFH2 and cTFH17, but not cTFH1 subsets were higher in NoTD than TD participants. However, we observed that ex-vivo expression of activation and homing markers were higher in TD than in NoTD participants, particularly after challenge. Moreover, cTFH subsets produced higher levels of S. Typhi-specific responses (cytokines/chemokines) in both the immunization and challenge phases. Interestingly, unsupervised analysis revealed unique clusters with distinct signatures for each cTFH subset that may play a role in either the development or prevention of typhoid disease. Importantly, we observed associations between frequencies of defined cTFH subsets and anti-S. Typhi antibodies. Taken together, our results suggest that circulating TFH2 and TFH17 subsets might play an important role in the development or prevention of typhoid disease. The contribution of these clusters was found to be distinct in the immunization and/or challenge phases. These results have important implications for vaccines aimed at inducing long-lived protective T cell and antibody responses

Anomalous dimensions and phase transitions in superconductors

The anomalous scaling in the Ginzburg-Landau model for the superconducting phase transition is studied. It is argued that the negative sign of the $\eta$ exponent is a consequence of a special singular behavior in momentum space. The negative sign of $\eta$ comes from the divergence of the critical correlation function at finite distances. This behavior implies the existence of a Lifshitz point in the phase diagram. The anomalous scaling of the vector potential is also discussed. It is shown that the anomalous dimension of the vector potential $\eta_A=4-d$ has important consequences for the critical dynamics in superconductors. The frequency-dependent conductivity is shown to obey the scaling $\sigma(\omega)\sim\xi^{z-2}$. The prediction $z\approx 3.7$ is obtained from existing Monte Carlo data.Comment: RevTex, 20 pages, no figures; small changes; version accepted in PR