THYROID DYSFUNCTION FOLLOWING ALPHA-INTERFERON TREATMENT FOR CHRONIC HEPATITIS C

In order to evaluate the influnces of IFNα on thyroid function, thyroid-stimulating hormone (TSH), total thyroxine (T4), free T4, tri-iodothyronine (T3), and thyroxine-binding globulin were examined in IFNα-treated 351 patients with chronic hepatitis C before and during therapy. As therapy, either 3 million units (MU) of human lymphoblastoid IFNα or 9MU of recombinant IFNα2a was administrated daily for the initial two weeks followed by three times a week for 22 weeks. There were nine patients showing thyroid dysfunction during IFNα therapy. They consist of one relapse of Graves' disease, one relapse of Hashimoto thyroiditis, one development of apparent thyroid insufficiency from subclinical hypothyroidism, five cases with transient hyperthyroidism and one case with transient hypothyroidism. T4 and T3 levels in most patients who transiently developed thyroid dysfunction were normalized spontaneously after the discontinuation of IFNα. Thyroid-related autoantibodies were positive in 4 patients before IFNα therapy and newly developed in one patient during therapy. Attention should be paid first to the previous histories of autoimmune thyroid diseases and the existence of thyroid-related autoantibodies for the prediction of development of thyroid dysfunction during IFNα therapy. In addition, serial examinations of TSH, T3 and T4 should be also necessary for early detection of transient thyroid dysfunction during IFNα therapy

The degree of microRNA-34b/c methylation in serum-circulating DNA is associated with malignant pleural mesothelioma

Objectives: Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis. microRNA-34b/c (miR-34b/c), which plays an important role in the pathogenesis of MPM, is frequently downregulated by DNA methylation in approximately 90% of MPM cases. In this study, we estimated the degree of miR-34b/c methylation in serum-circulating DNA using a digital methylation specific PCR assay (MSP). Materials and methods: A real-time MSP assay was performed using the SYBR Green method. The melting temperature (Tm) of each PCR product was examined using a melting curve analysis. For a digital MSP assay, 40 wells were analyzed per sample. A total of 110 serum samples from 48 MPM cases, 21 benign asbestos pleurisy (BAP) cases, and 41 healthy volunteers (HVs) were examined. Results: Positive range of Tm value for miR-34b/c methylation was defined as 77.71-78.79 degrees C which was the mean 3 standard deviations of 40 wells of a positive control. The number of miR-34b/c methylated wells was counted per sample according to this criterion. The number of miR-34b/c methylated wells in MPM cases was significantly higher than that in BAP cases (P = 0.03) or HVs (P < 0.001). Advanced MPM cases tended to have higher number of miR-34b/c methylated wells than early MPM cases. Receiver-operating characteristic (ROC) curve analysis revealed that three number of miR-34b/c methylated wells per sample was the best cut-off of positivity of MPM with a 67% of sensitivity and a 77% specificity for prediction. The area under the ROC curve was 0.77. Conclusions: Our digital MSP assay can quantify miR-34b/c methylation in serum-circulating DNA. The degree of miR-34b/c methylation in serum-circulating DNA is associated with MPM, suggesting that this approach might be useful for the establishment of a new detection system for MPM

Phamacogenomics of Clozapine-Induced Agranulocytosis

Background: Clozapine-induced agranulocytosis (CIA)/clozapine-induced granulocytopenia (CIG) (CIAG) is a life-threatening event for schizophrenic subjects treated with clozapine. Methods: To examine the genetic factor for CIAG, a genome-wide pharmacogenomic analysis was conducted using 50 subjects with CIAG and 2905 control subjects. Results: We identified a significant association in the human leukocyte antigen (HLA) region (rs1800625, p = 3.46 × 10−9, odds ratio [OR] = 3.8); therefore, subsequent HLA typing was performed. We detected a significant association of HLA-B*59:01 with CIAG (p = 3.81 × 10−8, OR = 10.7) and confirmed this association by comparing with an independent clozapine-tolerant control group (n = 380, p = 2.97 × 10−5, OR = 6.3). As we observed that the OR of CIA (OR: 9.3~15.8) was approximately double that in CIG (OR: 4.4~7.4), we hypothesized that the CIG subjects were a mixed population of those who potentially would develop CIA and those who would not develop CIA (non-CIA). This hypothesis allowed the proportion of the CIG who were non-CIA to be calculated, enabling us to estimate the positive predictive value of the nonrisk allele on non-CIA in CIG subjects. Assuming this model, we estimated that 1) ~50% of CIG subjects would be non-CIA; and 2) ~60% of the CIG subjects without the risk allele would be non-CIA and therefore not expected to develop CIA. Conclusions: Our results suggest that HLA-B*59:01 is a risk factor for CIAG in the Japanese population. Furthermore, if our model is true, the results suggest that rechallenging certain CIG subjects with clozapine may not be always contraindicated

Ferroquadrupole ordering and Gamma_5 rattling motion in clathrate compound Ce_3Pd_20Ge_6

Lattice effects in a cerium based clathrate compound Ce_3Pd_20Ge_6 with a cubic Cr_23C_6-type structure have been investigated by ultrasonic and thermal expansion measurements. Elastic softenings of (C_11-C_12)/2 and C_44 proportional to the reciprocal temperature 1/T above T_Q1 = 1.25 K are well described in terms of the quadrupole susceptibility for the ground state Gamma_8 quartet. A huge softening of 50 % in (C_11-C_12)/2 and a spontaneous expansion DL/L = 1.9x10^-4 along the [001] direction in particular indicate the ferroquadrupole ordering of O_2^0 below T_Q1. The elastic anomalies associated with the antiferromagnetic ordering at T_N2 = 0.75 K and the incommensurate antiferromagnetic ordering are also found. Notable frequency dependence of C_44 around 10 K is accounted for by the Debye-type dispersion indicating a Gamma_5 rattling motion of an off-center Ce ion along the [111] direction with eight fractionally occupied positions around the 4a site in a cage. The thermally activated Gamma_5 rattling motion obeying a relaxation time t = t_0exp(E/k_BT) with an attempt time t_0 = 3.1x10^-11 sec and an activation energy E = 70 K dies out with decreasing temperature, and then the off-center tunneling state of Ce ion in the 4a-site cage will appear at low temperatures.Comment: 11 pages, 15 figures, to be published on Phys. Rev.

Anisotropic magnetic phase diagram of the Kondo-lattice compound Ce3Pd20Ge6 : Observation of antiferromagnetic and quadrupolar ordering

From the measurement of the specific heat of single crystalline samples of Ce3Pd20Ge6, we have constructed magnetic phase diagrams for a magnetic field up to 4 T, which disclose a pronounced anisotropy along the three principal directions of [100], [110], and [111]. We have found that both the quadrupolar and antiterromagnetic ordering temperatures exhibit distinct directional dependences on the external magnetic field and that new phase transitions evolve in the antiferromagnetic phase as well as in the ordered quadrupolar phase. These facts strongly suggest the existence of a complicated form of anisotropic interaction between the electric quadrupolar moment and the magnetic dipolar moment. The present result is briefly discussed in comparison with the reported one for CeB6

Speech Misperception: Speaking and Seeing Interfere Differently with Hearing

<div><p>Speech perception is thought to be linked to speech motor production. This linkage is considered to mediate multimodal aspects of speech perception, such as audio-visual and audio-tactile integration. However, direct coupling between articulatory movement and auditory perception has been little studied. The present study reveals a clear dissociation between the effects of a listener’s own speech action and the effects of viewing another’s speech movements on the perception of auditory phonemes. We assessed the intelligibility of the syllables [pa], [ta], and [ka] when listeners silently and simultaneously articulated syllables that were congruent/incongruent with the syllables they heard. The intelligibility was compared with a condition where the listeners simultaneously watched another’s mouth producing congruent/incongruent syllables, but did not articulate. The intelligibility of [ta] and [ka] were degraded by <i>articulating</i> [ka] and [ta] respectively, which are associated with the same primary articulator (tongue) as the heard syllables. But they were not affected by <i>articulating</i> [pa], which is associated with a different primary articulator (lips) from the heard syllables. In contrast, the intelligibility of [ta] and [ka] was degraded by <i>watching</i> the production of [pa]. These results indicate that the articulatory-induced distortion of speech perception occurs in an articulator-specific manner while visually induced distortion does not. The articulator-specific nature of the auditory-motor interaction in speech perception suggests that speech motor processing directly contributes to our ability to hear speech.</p> </div

Effects of incongruent subtasks on syllable intelligibility.

<p>The mean and standard error (N = 10) of the correct response rates for auditory stimuli [pa], [ta], and [ka] when silently articulating (motor) and watching (visual) incongruent syllables, subtracted from their corresponding control levels, are shown.</p

Auditory stimulus and subtask.

<p>The auditory stimulus was embedded in white noise to exclude the possibility of participants hearing their own speech under the motor condition, where the signal-to-noise ratio was set at 5 dB. The noise was faded in and out linearly over 0.5 s. The stimulus was preceded by four clicks at 0.67 s intervals, which provided the participants with a cue to silently articulate a syllable under the motor condition. Under the motor condition, the syllables to be articulated by the participants were first presented visually in Japanese characters, which then disappeared at the second click. The participants silently articulated syllables three times in time with the third and fourth clicks and the onset of the stimulus. Under the visual condition, videos of a speaker’s face producing syllables were presented, which were synchronized with the auditory stimulus. The initial frame of each video was presented from the noise onset to the stimulus onset.</p

Syllable intelligibility.

<p>The mean and standard error (N = 10) of the correct response rates for auditory stimuli [pa], [ta], and [ka] (from top to bottom panels) are shown. Each color indicates a subtask syllable ([pa], [ta], and [k]) under motor (silently articulating) and visual (watching mouth) conditions. The open bars represent the control (auditory-only) condition.</p