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A case of Marchiafava-Bignami disease (MBD) is presented using magnetic resonance imaging (MRI). A patient with a long history of alcoholism developed a gait disturbance with involuntary movements at the lower extremities. MRI scans taken at the onset showed no particular abnormalities. He progressed to a coma 10 days later. MRI scans taken 20 days after the onset showed a focal lesion at the genu of the corpus callosum and he was diagnosed as having MBD. In addition, multiple lesions were observed in bilateral frontoparietal subcortical white matter. These lesions demonstrated similar intense MRI signals as the corpus callosum.

The Japanese Rhythm Management Trial for Atrial Fibrillation (J-RHYTHM study) is a randomized comparative evaluation of rate control and rhythm control, both combined with antithrombotic therapy, as therapeutic strategies for the treatment of atrial fibrillation (AF). This study differs from the earlier AFFIRM and RACE studies in that it has a composite primary end-point representing mortality and also physical/psychological disablement (total mortality, symptomatic cerebral infarction, systemic embolism, major bleeding, hospitalization for heart failure requiring intravenous administration of diuretics, and patient disablement). Patients' will to change the therapeutic strategy to the other is also considered as an end-point representing disablement under the assigned strategy. The secondary end-point includes quality of life scores and the efficacy and safety of drugs used in treating AF. The J-RHYTHM study emphasizes patient-reported experience and perception of AF-specific disablement, and the safety of antiarrhythmics available in Japan; it will follow 2600 patients treated at more than 150 sites in Japan for a 3-year period.

In Nepal, we tested 300 males for glucose-6-phosphate dehydrogenase (G6PD) activity. Two subjects were G6PD deficient (0.67%). Compared with normal controls, G6PD activity was 12% and 26%, respectively. The hemoglobin concentration of these two subjects was normal. We extracted genomic DNA from whole blood and read all sequences of G6PD. Both subjects had the same replacement of 563C>T, which was classified as G6PD Mediterranean. The amino acid might change from Ser to Phe at codon 188. These subjects also had a replacement of 1311C>T, which caused no replacement of an amino acid. A similar replacement pattern of G6PD Mediterranean is described from persons living in Mediterranean countries and Middle East countries. However, G6PD Mediterranean found in India and Pakistan has no replacement at nucleotide 1311. Thus, these two subjects in Kathmandu, Nepal, would be closer to people in Middle East countries than people in India. This is the first study of molecular analysis for G6PD deficiency in Nepal.

Background: We have investigated the effects of various vasodilators on smooth muscle relaxation during acute recoil with guinea-pig aorta to find effective therapies to prevent acute recoil at percutaneous transluminal coronary angioplasty (PTCA)., Methods: Muscle strips from guinea-pig aorta without endothelium were placed in a bath filled with modified Krebs solution. The strip was isotonically stretched with a tension of 9 mN for 1 min, and then isometric tension was measured until the tension reached a steady state. Various vasodilators were applied during isometric tension measurement., Results: When no drug was applied (control), isometric tension reached a steady state within 20 min. The steady state was approximately 10% lower (more relaxed) than the stretched level. When isosorbide dinitrate (ISDN, 1 mM) was applied during isometric measurement, 18.7+/-5.3% greater relaxation occurred than in control relaxation (P<0.05, n=5). When nicorandil (1 mM) was applied, the following relaxation was 18.6+/-5.7% greater than control (P<0.05, n=8). The simultaneous application of glibenclamide (1 mM) completely inhibited such additional relaxation by nicorandil. Application of nifedipine (10 microM) caused a 12.9+/-2.5% greater relaxation than control (P=0.066, n=4). The first metabolite of sarpogrelate (BP984, 10 microM) caused much greater relaxation than control (23.7+/-7.9%, P<0.05, n=6). Amlodipine (10 microM), phentolamine (10 microM), and sarpogrelate (10 microM) had no influence on the relaxation of the strip., Conclusions: ISDN, nicorandil and BP984 significantly increase relaxation of the muscle strips after stretching compared to the control. These vasodilators may reduce acute recoil of the smooth muscle after PTCA.

Although aging accompanies specific pathological changes, including thrombosis and organ sclerosis, the underlying mechanisms of these processes remain to be elucidated. In the present study, we analyzed the gene expression of plasminogen activator inhibitor-1 (PAI-1), a key molecule in the development of thrombosis, in a murine model of aging, klotho mutant ( kl/kl) mice. Active PAI-1 antigen in plasma and PAI-1 mRNA in several tissues were strikingly elevated in kl/kl mice as compared with wild-type mice. This increased PAI-1 expression was age dependent and linked to the development of ectopic calcification and glomerular fibrin deposition in the kidneys. In situ hybridization analysis of kl/kl mice demonstrated that strong signals for PAI-1 mRNA were localized in renal tubular epithelial cells, cardiomyocytes, adrenal medullar cells, and smooth muscle and endothelial cells in Mönckeberg's arteriosclerotic vessels. Renal glomerular fibrin deposition, as evaluated immunohistochemically, was occasionally observed only in kl/kl mice, and the number of fibrin-positive glomeruli increased as the kl/kl mice aged. These observations suggest that in the process of aging the PAI-1 gene expression is increased, contributing to the development of thrombosis.

Ligand-receptor internalization has been traditionally regarded as part of the cellular desensitization system. Low-density lipoprotein receptor-related protein (LRP) is a large endocytosis receptor with a diverse array of ligands. We recently showed that LRP binds heparin-binding growth factor midkine. Here we demonstrate that LRP mediates nuclear targeting by midkine and that the nuclear targeting is biologically important. Exogenous midkine reached the nucleus, where intact midkine was detected, within 20 min. Midkine was not internalized in LRP-deficient cells, whereas transfection of an LRP expression vector restored midkine internalization and subsequent nuclear translocation. Internalized midkine in the cytoplasm bound to nucleolin, a nucleocytoplasmic shuttle protein. The midkine-binding sites were mapped to acidic stretches in the N-terminal domain of nucleolin. When the nuclear localization signal located next to the acidic stretches was deleted, we found that the mutant nucleolin not only accumulated in the cytoplasm but also suppressed the nuclear translocation of midkine. By using cells that overexpressed the mutant nucleolin, we further demonstrated that the nuclear targeting was necessary for the full activity of midkine in the promotion of cell survival. This study therefore reveals a novel role of LRP in intracellular signaling by its ligand and the importance of nucleolin in this process.

KaiA KaiB and KaiC are essential circadian clock proteins in the unicellular cyanobacterium Synechococcus elongatus PCC 7942. KaiA protein activates transcription of the kaiBC operon, which is believed to be a crucial step in the oscillating feedback loop of cyanobacteria. In this study, approximately approximately 400 mutations were introduced into kaiA by PCR-based mutagenesis, and rhythmic phenotypes of these mutants were studied by a bioluminescence reporter. In contrast to mutations in KaiB or KaiC, the vast majority of KaiA mutations extended the period and only rarely shortened it. The period could be extended to 35 h without lowering the mean or peak levels of kaiBC expression. However, several mutations resulted in low-amplitude oscillations or arrhythmia, which were accompanied by lowered kaiBC transcription. These results imply that the KaiA protein can change the period length of the circadian rhythm directly (through an unknown biochemical mechanism) or indirectly (by lowering kaiBC expression). Specific mutations of KaiA were identified in 34 mutants. While mutations mapped to various locations of the KaiA sequence, two clusters of period-altering mutations were found. This suggested that these regions are important domains of the KaiA protein for defining the period length. On the other hand, different sequences within KaiA to which arrhythmic mutations were mapped are important to enhance kaiBC expression.

To assess the validity of accelerometry in measuring daily physical activity, the energy consumption calculated by accelerometry, with respiratory gas analysis as a reference, was evaluated in 45 non-athletes during various exercise tests. Subjects were required to (1) walk on a treadmill ergometer at various speeds, (2) walk on a treadmill ergometer at a fixed speed and with a stride of 20% more or 20% less than that when walking freely, (3) walk on a treadmill ergometer at a fixed speed wearing either sneakers or leather-soled shoes, and (4) cycle on a bicycle ergometer. There were strong linear relationships between the measurements during the progressively graded treadmill test, with an overall Pearson correlation coefficient of 0.97. The mean estimated difference ranged from -0.77 to 0.27 kcal/min and the coefficients of variation from 13.2% to 22.2%. However, the difference between the methods was not negligible for individual subjects. Accelerometry overestimated energy expenditure during short-step walking, and underestimated it during long-step walking. No significant difference in energy expenditure was found according to the type of shoes worn. Cycling activity was not recorded by accelerometry. Accelerometry is a reasonably accurate and feasible method for evaluating the physical activities of non-athletes, and could be a common tool for epidemiological research and health promotion despite its limitations.

This article aims to clarify the clinical significance of changes in electrocardiographic (ECG) R-wave voltage on chest leads from 1 to 4 weeks in patients with acute anterior myocardial infarction (MI) in combination with echocardiographic findings and dual scintigraphic findings. Seventy-one patients with acute anterior MI who underwent emergency revascularization were subjected to ECG and echocardiography, at both 1 and 4 weeks, and to thallium-201 (TI) and iodine-123-beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) about 1 week after the onset of MI. The total sum of ECG R-wave voltage on each chest lead was calculated. The mean defect ratio on TI and that on BMIPP derived from circumferential profile curve analysis were calculated. The percentage defect-discordant ratio of both SPECT images [(%) discordance on TI/BMIPP] was obtained. The percentage increase ratio of ECG R-wave voltage on chest leads [(%) increase of R wave] and the increase of left ventricular ejection fraction (DeltaEF) from 1 to 4 weeks were obtained. There were significant correlations between the (%) increase of R wave and the DeltaEF as well as between the (%) increase of R wave and the (%) discordance on TI/BMIPP (r =.63, P <.001; r =.74, P <.001). The reversibility of ECG R-wave voltage was related to cardiac functional improvement in addition to the discordance on the 2 images. Monitoring of changes in ECG R-wave voltage on chest leads is useful to detect the presence of myocardial viability and to evaluate functional evolution in patients with acute anterior MI.

Introduction: Transient T wave changes after cessation of preexcitation have been attributed to cardiac memory. However, there have been no reports on the effects of long-term cardiac memory on repolarization dispersion before and after catheter ablation in patients with Wolff-Parkinson-White (WPW) syndrome., Methods and Results: We investigated 47 patients with an accessory pathway (AP; 24 manifest left-sided, 14 manifest right-sided, and 9 concealed left-sided). Repolarization dispersion was analyzed by two methods, recovery time (RT) dispersion and newly proposed T wave width (WT), from 87-lead body surface maps before, 1 day after, and 7 days after catheter ablation. RT dispersion and WT were significantly correlated before, 1 day after, and 7 days after catheter ablation (r = 0.78). In patients with preexcitation, RT dispersion and WT increased significantly (P < 0.05) 1 day after catheter ablation (178 +/- 32 msec and 172 +/- 30 msec) compared with those before (154 +/- 24 msec and 156 +/- 18 msec) and 7 days after catheter ablation (147 +/- 19 msec and 156 +/- 16 msec), respectively. However, there were no significant changes in RT dispersion and WT before and after catheter ablation in concealed WPW syndrome., Conclusion: The findings suggest that the abrupt changes in activation sequence increase repolarization dispersion in the presence of previous cardiac memory, and that the dispersion decreases days or weeks after alteration of activation sequence by catheter ablation, with development of new cardiac memory in patients with manifest WPW syndrome.

We have identified a novel member of the nuclear receptor superfamily from the silkworm Bombyx mori, and named it as BmHR78, the B. mori hormone receptor. The DNA binding domain of BmHR78 shows high similarities to those of Tenebrio molitor hormone receptor 78, Drosophila hormone receptor 78, and mammalian testicular receptor 2, whereas the ligand binding domain is not well conserved. Northern blot analysis showed that BmHR78 gene was most abundantly expressed in the testis. From the fourth to fifth instar, BmHR78 gene was constantly expressed in the testis. In the anterior silk gland, the level of BmHR78 gene expression was developmentally changed. From day 10.0 to 11.0 in the fifth instar, another BmHR78 transcript with the smaller size appeared. Ultraspiracle (USP) isoform also appeared at the same stages in this tissue. BmHR78 forms not only a homodimer, but also a heterodimer with USP in a yeast two hybrid assay. The direct interaction between BmHR78 and USP was confirmed by pull down assay. Deletion mutant analysis showed that BmHR78 interacts with USP via the ninth heptad repeat in helix ten of the E region. This repeat is well conserved in RXR and its heterodimer partners, and shown to be an interface for their dimerization. In insect, only the ecdysone receptor and hormone receptor 38 are known thus far to dimerize with USP. Thus, BmHR78 is a third dimerization partner for USP and may modulate the molecular action of USP, including the ecdysone signal cascades.

We investigated the relationships among Factor VII coagulant activity (FVIIc), genetic polymorphisms of Factor VII (FVII) and coronary artery disease (CAD) in 380 unrelated Japanese individuals (mean 64 years) who underwent coronary angiography and whose cholesterol levels were within normal range. CAD subjects were defined as those in whom one of the three major coronary arteries showed >50% narrowing after nitroglycerin administration. FVIIc was measured and the following polymorphisms of FVII were determined: R353Q polymorphism (M1, M2 alleles), -323 0/10 bp polymorphism (0, 10 alleles), hypervariable region 4 of intron 7 (HVR4; H5, H6, H7 alleles). FVIIc was slightly lower in M1M2/M2M2 than M1M1 (89.5+/-8.9%, 93.4+/-17.8%). Those with M2 and/or 10 allele have less chance of developing CAD (M2: OR 0.36, 95% CI 0.18-0.69, 10: OR 0.50, 95% CI 0.26-0.97). However, both alleles did not associate with myocardial infarction (MI). HVR4 was unrelated with CAD, nor with MI. In conclusion, M2 and/or 10 allele has protective effects on the developing CAD in individuals with a normal cholesterol level.

We found that infection of a rodent malaria, Plasmodium berghei, occurred when the sporozoites were injected into the skin, the muscle, the peritoneal cavity and the tail end. Mice, which were injected with sporozoites in the tail end and had the site cut 5 min later, did not develop malaria. We also found that mice developed malaria when malaria infective mosquitoes, Anopheles stephensi, were forced not to take blood but only to probe into the skin. Moreover, the mice probed by the infective mosquitoes were protected from malaria infection if the site was treated with Kyu (heat treatment) after the mosquitoes had probed. These findings indicate that malaria infection occurs not only by blood feeding of the infective mosquito but also by probing of the mosquito. Sporozoites injected into the skin remain at the injected site for at least 5 min, then migrate to the blood vessels and invade into the blood stream. At present, the mechanism is not clear, although we propose here the existence of the skin stage of malaria parasites before the liver stage and the blood stage.