993-40 Characteristics of the Atrial Signal-averaged Electrocardiograms in Patients with Sick Sinus Syndrome – the Presence of “Atrial Early Potential”

In sick sinus syndrome (SSS), pathophysiological abnormalities have been shown not only in the sinus node but also in the atrial muscle, especially of the perinodal portion. To investigate whether the electrophysiological abnormalities of atrial muscle in SSS would induce the characteristic P wavepattern, especially in the initial portion of the P wave, we studied 37 patients with SSS and 67 age-comparable control patients. using the P wave-triggered signal-averaged electrocardiography. Sixteen of 37 SSS patients had paroxysmal atrial fibrillation (Paf). Signal-averaged electrocardiograms were recorded with a band-pass filter of 40–300Hz and signals of 200 beats or more were averaged with the P wave-triggering technique. The P wave complexes of the three bipolar leads were combined into a spatial magnitude, and then the root mean square voltage for the initial 30ms (EP30) and the last 20m (LP20) of filtered P wave were measured. The duration (Ad) and root mean square voltage (RMS) of the total filtered P wave were also measured.ResultsSSS with PafSSS without PatControlEP30 (μV)2.55±1.17*2.16±0.98*3.93±1.23LP20 (μV)1.98±0.40#†2.79±1.043.35±1.76Ad (ms)145.8±16.1*†131.2±14.1123.7±11.7RMS (μV)6.20±0.415.82±0.826.20±1.47*p<0.0001#P<0.005p&lt;0.05 vs. Control†p&lt;0.01 vs SSS Without PatThe amplitude of initial portion of filtered P wave was significantly lower and the duration was longer in SSS patients with/without Paf than the controls, while there was no significant difference in the amplitude of the terminal portion between SSS patients without Paf and controls. The criteria of “EP30≤3.0μV and Ad&gt;130m” as defining “atrial early potential” gave a sensitivity of 76%, a specificity of 83% and a predictive accuracy of 81% for detection of patients with SSS. These results indicate that the low amplitude signals in the initial portion of filtered P wave were characteristic of SSS, so that the recognition of atrial early potential might be promising to identify patients with SSS

Effects of periodic robot rehabilitation using the Hybrid Assistive Limb for a year on gait function in chronic stroke patients

Using a robot for gait training in stroke patients has attracted attention for the last several decades. Previous studies reported positive effects of robot rehabilitation on gait function in the short term. However, the long-term effects of robot rehabilitation for stroke patients are still unclear. The purpose of the present study was to investigate the long-term effects of periodic gait training using the Hybrid Assistive Limb (HAL) on gait function in chronic stroke patients. Seven chronic stroke patients performed 8 gait training sessions using the HAL 3 times every few months. The maximal 10-m walk test and the 2-minute walking distance (2MWD) were measured before the first intervention and after the first, second, and third interventions. Gait speed, stride length, and cadence were calculated from the 10-m walk test. Repeated one-way analysis of variance showed a significant main effect on evaluation time of gait speed (F = 7.69, p < 0.01), 2MWD (F = 7.52, p < 0.01), stride length (F = 5.24, p < 0.01), and cadence (F = 8.43, p < 0.01). The effect sizes after the first, second, and third interventions compared to pre-intervention in gait speed (d = 0.39, 0.52, and 0.59) and 2MWD (d = 0.35, 0.46, and 0.57) showed a gradual improvement of gait function at every intervention. The results of the present study showed that gait function of chronic stroke patients improved over a year with periodic gait training using the HAL every few months

Identification of Tam41 maintaining integrity of the TIM23 protein translocator complex in mitochondria

Newly synthesized mitochondrial proteins are imported into mitochondria with the aid of protein translocator complexes in the outer and inner mitochondrial membranes. We report the identification of yeast Tam41, a new member of mitochondrial protein translocator systems. Tam41 is a peripheral inner mitochondrial membrane protein facing the matrix. Disruption of the TAM41 gene led to temperature-sensitive growth of yeast cells and resulted in defects in protein import via the TIM23 translocator complex at elevated temperature both in vivo and in vitro. Although Tam41 is not a constituent of the TIM23 complex, depletion of Tam41 led to a decreased molecular size of the TIM23 complex and partial aggregation of Pam18 and -16. Import of Pam16 into mitochondria without Tam41 was retarded, and the imported Pam16 formed aggregates in vitro. These results suggest that Tam41 facilitates mitochondrial protein import by maintaining the functional integrity of the TIM23 protein translocator complex from the matrix side of the inner membrane

Human Desmocollin 1 (Dsc1) Is an Autoantigen for the Subcorneal Pustular Dermatosis Type of IgA Pemphigus

IgA pemphigus showing IgA anti-keratinocyte cell surface autoantibodies is divided into subcorneal pustular dermatosis (SPD) and intraepidermal neutrophilic IgA dermatosis (IEN) types. We previously showed by immunoblotting that IgA from some IgA pemphigus patients reacted with bovine desmocollins (Dsc), but not human Dsc. To determine the antigen for IgA pemphigus, we focused on conformation-dependent epitopes of Dsc, because sera of patients with classical pemphigus recognize conformation-sensitive epitopes of desmogleins. We constructed mammalian expression vectors containing the entire coding sequences of human Dsc1, Dsc2, and Dsc3 and transiently transfected them into COS7 cells by lipofection. Immunofluorescence of COS7 cells transfected with single human Dscs showed that IgA antibodies of all six SPD-type IgA pemphigus cases reacted with the surface of cells expressing Dsc1, but not with cells expressing Dsc2 or Dsc3. In contrast, none of seven IEN-type IgA pemphigus cases reacted with cells transfected with any Dscs. These results convincingly indicate that human Dsc1 is an autoantigen for SPD-type IgA pemphigus, suggesting the possibility of an important role for Dsc1 in the pathogenesis of this disease. This study shows that a Dsc can be an autoimmune target in human skin disease

Structural and Expressional Alterations of Episomal and Integrated Human Papillomavirus Type 16 in Precancerous Lesions and Carcinomas of the Cervix.

HPV infection has long been implicated in the development of cervical car-cinoma. We have analyzed the HPV 16 genome structure and expression of the viral mRNA in cervical intraepithelial neoplasias (CINs) and cervical car-cinomas by using modified polymerase chain reaction (PCR) methods. Genome structure has been determined by PCR using multi-primer sets which are located in each open reading frames and then these results have been compared with the physical state of the viral DNA determined by two-dimensional electrophoresis. Furthermore, we have analyzed the expression of HPV 16 mRNA and genome structure using DNA and RNA simultaneously extracted from CINs and cervical carcinomas using PCR and reverse transcription (RT-) PCR. Our data showed that the DNA regions from the El to Ll region were delet-ed in two of three CINs containing episomal HPV 16 and three out of seven cervical carcinomas containing integrated HPV 16. However, the E6/E7 region was conserved in all the HPV 16-positive samples. RT-PCR analysis has determined the presence of mRNA species which could encode the E6, E6*I, E6*II, E7, E2, E2 ? C, E1^E4, E1^E2 ? C, E4, E2 ? C-E5 and L2 proteins. The overall results of DNA and mRNA analyses in cervical lesions indicated that the expression patterns of the early and late transcripts studied were not specifically related to the grade of malignancy and the physical state or the deletion of the viral genome. Furthermore, alterations in the splicing pat-terns of HPV 16 transcripts may not be involved in tumor progression

Relevance of the Core 70 and IL-28B polymorphism and response-guided therapy of peginterferon alfa-2a ± ribavirin for chronic hepatitis C of Genotype 1b: a multicenter randomized trial, ReGIT-J study

BACKGROUND: We conducted a multicenter randomized clinical trial to determine the optimal treatment strategy against chronic hepatitis C virus (HCV) with genotype 1b and a high viral load (G1b/high). METHODS: The study subjects included 153 patients with G1b/high. Patients were initially treated with PEG-IFNα-2a alone and then randomly assigned to receive different treatment regimens. Ribavirin (RBV) was administered to all patients with HCV RNA at week 4. Patients negative for HCV RNA at week 4 were randomly assigned to receive PEG-IFNα-2a (group A) or PEG-IFNα-2a/RBV (group B). Patients who showed HCV RNA at week 4 but were negative at week 12 were randomly assigned to receive weekly PEG-IFNα-2a (group C) or biweekly therapy (group D). Patients who showed HCV RNA at week 12 but were negative at week 24 were randomly assigned to receive PEG-IFNα-2a/RBV (group E) or PEG-IFNα-2a/RBV/fluvastatin (group F). RESULTS: Overall, the rate of sustained virological response (SVR) was 46 % (70/153). The total SVR rate in the group (A, D, and F) of response-guided therapy was significantly higher than that in the group (B, C, and E) of conventional therapy [70 % (38/54) versus 52 % (32/61), p = 0.049]. Although IL28-B polymorphism and Core 70 mutation were significantly associated with efficacy, patients with rapid virological response (RVR) and complete early virological response (cEVR) achieved high SVR rates regardless of their status of IL-28B polymorphism and Core 70 mutation. CONCLUSION: In addition to knowing the IL-28B polymorphism and Core 70 mutation status, understanding the likelihood of virological response during treatment is critical in determining the appropriate treatment strategy

Integration of In Vivo Genotoxicity and Short-term Carcinogenicity Assays Using F344 gpt Delta Transgenic Rats: In Vivo Mutagenicity of 2,4-Diaminotoluene and 2,6-Diaminotoluene Structural Isomers

An important trend in current toxicology is the replacement, reduction, and refinement of the use of experimental animals (the 3R principle). We propose a model in which in vivo genotoxicity and short-term carcinogenicity assays are integrated with F344 gpt delta transgenic rats. Using this model, the genotoxicity of chemicals can be identified in target organs using a shuttle vector λ EG10 that carries reporter genes for mutations; short-term carcinogenicity is determined by the formation of glutathione S-transferase placenta form (GST-P) foci in the liver. To begin validating this system, we examined the genotoxicity and hepatotoxicity of structural isomers of 2,4-diaminotoluene (2,4-DAT) and 2,6-diaminotoluene (2,6-DAT). Although both compounds are genotoxic in the Ames/Salmonella assay, only 2,4-DAT induces tumors in rat livers. Male F344 gpt delta rats were fed diet containing 2,4-DAT at doses of 125, 250, or 500 ppm for 13 weeks or 2,6-DAT at a dose of 500 ppm for the same period. The mutation frequencies of base substitutions, mainly at G:C base pairs, were significantly increased in the livers of 2,4-DAT–treated rats at all three doses. In contrast, virtually no induction of genotoxicity was identified in the kidneys of 2,4-DAT–treated rats or in the livers of 2,6-DAT–treated rats. GST-P–positive foci were detected in the livers of rats treated with 2,4-DAT at a dose of 500 ppm but not in those treated with 2,6-DAT. Integrated genotoxicity and short-term carcinogenicity assays may be useful for early identifying genotoxic and nongenotoxic carcinogens in a reduced number of experimental animals

Rare Influenza A (H3N2) Variants with Reduced Sensitivity to Antiviral Drugs

In 2007 and 2008 in Myanmar, we detected influenza viruses A (H3N2) that exhibited reduced sensitivity to both zanamivir and amantadine. These rare and naturally occurring viruses harbored a novel Q136K mutation in neuraminidase and S31N mutation in M2