Comprehensive data on ionising radiation from Fukushima Daiichi nuclear power plant in the town of Miharu, Fukushima Prefecture: The Misho Project.

Data related to radioactivity released from the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident on 15 March 2011 gathered by residents of Miharu, Fukushima Prefecture, and by Tohoku University are presented. These data sets consist of (1) the earliest radiation monitoring by a Geiger counter in the town, (2) ratios of radioactivity between (132)Te and (137)Cs for a wide area between Fukushima and Tokyo, (3) radiation measurement of soil samples collected from 18 school grounds, and (4) external radiation exposure of 1400 students using OSL badges. By combining and analysing these various data sets, a curve for the cumulative total external exposure as a function of time, with 16 : 00 h on 15 March 2011 being time zero, is obtained. The average cumulative external dosage is estimated to be 10 mSv (σ = 4.2 mSv) over 10 years. In addition, the initiative that the residents of Miharu took in response to the FDNPP accident, which became known as The Misho Project (MP), is documented; in particular, the time at which the municipality instructed the immediate ingestion of iodine tablets by those under the age of 40, 13 : 00 h on 15 March 2011, is assessed.

Oncolytic activity of Sindbis virus in human oral squamous carcinoma cells.

BACKGROUND: Sindbis virus (SIN) infection causes no or only mild symptoms (fever, rash, and arthralgia) in humans. However, SIN has a strong cytopathic effect (CPE) on various cancer cells. This study focuses on the oncolytic activity of SIN AR399 on oral cancer cells compared with reovirus, a well-known oncolytic virus that targets cancer cells. METHODS: We analysed the cytotoxicity and growth of SIN in 13 oral squamous cell carcinoma (OSCC) cell lines (HSC-2, HSC-3, HSC-4, Ca9-22, H-1, Sa-3, KON, KOSC-2, OK-92, HO-1-N1, SCC-4, SAT, SKN-3) and normal human oral keratinocytes (NHOKs). RESULTS: Sindbis virus infection induced CPE in 12 OSCC cell lines at a low multiplicity of infection (MOI) of 0.01, but not in the OSCC cell line, HSC-4 or NHOKs. Sindbis viral growth was not observed in NHOKs, whereas high SIN growth was observed in all OSCC cell lines, including HCS-4. The cytotoxicity and growth of SIN was the same as reovirus at an MOI of 20 in 12 OSCC cell lines. The CPE was shown, by terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labelling assays, to be apoptotic cell death. Furthermore, quantitative RT-PCR of mRNA in HSC-3 and HSC-4 cells after SIN infection showed that activation of caspases, cytochrome c, and IkappaBalpha was associated with SIN-induced apoptosis. CONCLUSION: As a replication-competent oncolytic virus, SIN may be a useful therapeutic modality for oral cancers.

Nuclear protein phosphokinases in normal and neoplastic tissues.

Protein phosphokinases were isolated from the nuclei of normal and fetal liver and neoplastic tissues. Chromatography on phosphocellulose columns resolved the normal and fetal liver kinases into five reproducible fractions. Each of the fractions differed in optimal divalent cation and substrate requirements. Hepatic proliferation was accompanied by quantitative changes in the kinase activity profiles (with endogenous phosphoprotein as natural substrate). An additional phosphoprotein kinase activity stimulated by Mn2+ was found in the nuclei of malignant cells. This tumor-specific kinase could not be detected either in tumor cytoplasm or in fetal or regenerating liver nuclei. Mn2+-dependent phosphoprotein kinase from Novikoff hepatoma phosphorylated only one major protein band detectable by polyacrylamide gel electrophoresis. This substrate could not be detected in chromatin of normal tissues.

[Aortic root enlargement in elderly patients].

From January 2003 to June 2005, 12 elderly patients with severe aortic stenosis underwent aortic root enlargement (ARE) by Nicks procedure. Their ages ranged from 74 to 87 with a mean of 79.3. Stented bioprosthesis were used in 11 cases. There was no death. Cardiothoracic ratio on chest X-ray decreased from 59.4 to 53.6% and New York Heart Association (NYHA) functional class improved from 3.4 to 1.3. Echocardiography also showed remarkable improvement, in peak pressure gradient (PG) from 98.3 to 20.7 mmHg, in left ventricular mass index (LVMI) 181 to 137 g/m2. LVM and LVMI regression rates were 25.3 and 22.3%, respectively. Comparative study of those with ARE alone and those with combined operation showed much hazardous effect in the latter, but no significant difference in echocardiographic findings postoperatively. ARE by Nicks procedure, if it could be performed without concomitant procedure, is a safe and effective option also in elderly patients with small aortic annulus.

Pathological changes in levels of three small stress proteins, alphaB crystallin, HSP 27 and p20, in the hindlimb muscles of dy mouse.

Using three different analyses, we investigated the levels of the three small stress proteins alphaB crystallin, HSP 27 and p20 in the slow-twitch soleus muscle and fast-twitch tibialis anterior muscle of normal and dy mice. All of these analyses (immunoassay, Western blot and immunohistochemistry) showed markedly increased levels of these stress proteins in fast-twitch type muscle (tibialis anterior muscle) of dy mouse. In contrast, the levels of alphaB crystallin, HSP 27 and p20 of dy mouse were reduced in slow-twitch type muscle (soleus muscle). Manipulation of this protective response may reduce injury and may have potential therapeutic application in congenital muscular dystrophy (CMD), which possesses a deficiency of laminin-alpha2 chain in muscle fiber basement similar to dy mouse.

Differential adaptation of growth and differentiation factor 8/myostatin, fibroblast growth factor 6 and leukemia inhibitory factor in overloaded, regenerating and denervated rat muscles.

Mice genetically deficient in growth and differentiation factor 8 (GDF8/myostatin) had markedly increased muscle fiber numbers and fiber hypertrophy. In the regenerating muscle of mice possessing FGF6 mutation, fiber remodeling was delayed. Although myostatin and FGF6 may be important for the maintenance, regeneration and/or hypertrophy of muscle, little work has been done on the possible role of these proteins in adult muscle in vivo. Using Western blot and immunohistochemical analysis, we investigated, in rats, the distribution of myostatin, FGF6 and LIF proteins between slow- and fast-type muscles, and the adaptive response of these proteins in mechanically overloaded muscles, in regenerating muscles following bupivacaine injection and in denervated muscles after section of the sciatic nerve. The amounts of myostatin and LIF protein were markedly greater in normal slow-type muscles. In the soleus muscle, myostatin and LIF proteins were detected at the site of the myonucleus in both slow-twitch and fast-twitch fibers. In contrast, FGF6 protein was selectively expressed in normal fast-type muscles. Mechanical overloading rapidly enhanced the myostatin and LIF but not FGF6 protein level. In the regenerating muscles, marked diminution of myostatin and FGF6 was observed besides enhancement of LIF. Denervation of fast-type muscles rapidly increased the LIF, but decreased the FGF6 expression. Therefore, the increased expressions of myostatin and LIF play an important role in muscle hypertrophy following mechanical overloading. The marked reduction of FGF6 in the hypertrophied and regenerating muscle would imply that FGF6 regulates muscle differentiation but not proliferation of satellite cells and/or myoblasts.

The adaptive response of MyoD family proteins in overloaded, regenerating and denervated rat muscles.

Using Western blot analysis, we investigated whether the amount of myogenic regulatory factors differs in slow-type and fast-type muscles. In addition, we examined the adaptive response of myogenic regulatory factor protein in the overloaded rat muscles by the ablation of synergists, in the regenerating muscles following bupivacaine injection and in the denervated muscle. The amount of myogenin protein in the slow-type muscle was markedly greater. In contrast, the proteins MyoD and Myf-5 were selectively accumulated in the fast-type muscles. A gradual down-regulation of MyoD and Myf-5 proteins was detected in the denervated fast-type muscles, but not in the myogenin protein content. A rapid down-regulation of myogenic regulatory factor protein was observed both of the mechanically overloaded and in the regenerating muscles. These results indicate that the fast-type-specific gene expression in muscle is modulated by MyoD and Myf-5 proteins and suggest that myogenin protein plays an important role in the reconstruction of damaged neuromuscular connections.

The HDL2/HDL3 ratio in menopause.

OBJECTIVES: The influence of the menopause on the HDL2/HDL3 ratio was assessed in association with hypertriglyceridemia. METHODS: Fasting blood samples were collected from 607 patients. Commercially available enzymatic methods were used for determination of TG, and total HDL-C. HDL2 and HDL3 were measured by ultracentrifugation. RESULTS: The HDL2/HDL3 ratio had a strong negative correlation with TG (r=-0.272, P<0.0001 and r=-0.314, P<0.0001) in both pre- and postmenopausal women. No significant differences were observed in HDL2, HDL3, and HDL2/HDL3 ratio between pre- and postmenopausal women without hypertriglyceridemia. Postmenopausal women had a significantly higher HDL2/HDL3 ratio than premenopausal women with hypertriglyceridemia. CONCLUSIONS: These results indicate that menopausal status not only increases plasma LDL-cholesterol and triglyceride levels, but also increases the HDL2/HDL3 ratio when associated with elevation of plasma triglyceride levels. These changes may increase the risk for CHD due to enlargement of the lipid pool.

Cyclic guanidines. 17. Novel (N-substituted amino)imidazo[2,1-b]quinazolin-2 ones: water-soluble platelet aggregation inhibitors.

A series of novel 1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2-one derivatives substituted with a secondary amino group has been prepared and tested for the activities of inhibiting platelet aggregation in rats in vitro and ex vivo. Most of the compounds were found to be the potent inhibitors of platelet aggregation. Some of the active compounds were soluble in water and effective via iv infusion in rats. Structure-activity relationships have indicated that a lipophilic secondary amino group located at position 6 or 7 contributed to retention of potent activity. Among the compounds studied, 7-piperidino-1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2- one (13 g,DN-9693) was the most favorable compound.

Cyclic guanidines. 14. Imidazo[1,2-a]thienopyrimidin-2-one derivatives as blood platelet aggregation inhibitors.

A series of novel 1,2,3,5-tetrahydroimidazo[1,2-a]thieno[2,3-d]-, -[3,2,-d]-, and -[3,4-d]pyrimidin-2-one derivatives has been prepared and tested for the activity of inhibiting platelet aggregation in rats in vitro and ex vivo. These compounds were synthesized through the following reactions: sodium borohydride reduction of 2,4-dichlorothienopyrimidines, followed by ethoxycarbonylmethylation and successive amination. Most of the compounds were found to be potent inhibitors of blood and platelet aggregation. Structure-activity relationships have indicated the essential contribution of the lactam structure and lipophilic substituents on the thiophene ring to the effective interaction of the compounds with a receptor site on the platelet. Among the compounds studied, 1,2,3,5,6,7,8,9-octahydro-[1]benzothieno[2,3-d]imidazo[1,2-a]pyrimidin-2-one (9m) exhibited the most favorable activity.

High-frequency magnetic oscillations evoked by posterior tibial nerve stimulation.

Magnetocephalographic recordings of the primary somatosensory response (P37m) and high-frequency oscillations (HFOs) evoked by posterior tibial nerve stimulation were obtained in normal subjects. Electrical stimuli were delivered to the posterior tibial nerve and magnetic recordings were taken over the superior aspect of the left hemisphere with a 37-channel biomagnetometer. In order to separate the high-frequency oscillations from the underlying P37m, the wide-band (0.1-1200 Hz) recorded responses were digitally filtered with a 500-800 Hz band-pass filter. The localization of the HFOs were estimated to be in somatosensory area 3b, very close to the P37m source. Our data suggest that the HFOs are somatotopically arranged in the primary somatosensory cortex, and are a ubiquitous phenomenon of the primary somatosensory cortex.

Serial activation of distinct cytoarchitectonic areas of the human S1 cortex after posterior tibial nerve stimulation.

MEG recordings visualized non-invasively a dynamic anterior-posterior activation in the pyramidal cell population of the human primary somatosensory cortex (S1) after posterior tibial nerve stimulation. Somatosensory evoked fields (SEFs) were recorded over the foot area in response to right posterior tibial nerve stimulation at the ankle in six normal subjects. A newly developed MEG vector beamformer technique applied to the SEFs revealed two distinct sources in the mesial wall of the left hemisphere around the primary P37m response typically separated by 1.3 cm. The first source was located in area 3b and oriented toward the contralateral hemisphere. The second source was assumed to be in an area near the marginal sulcus and the source orientation was directed posteriorly. The first source began to be active during the initial slope of the P37m. The second source was active after the P37m peak and the signal intensities of the first and second sources were equal at a mean latency of 2.6 ms after the peak of P37m. Then the first source became inactive and the second source was dominant after about 5 ms post-P37m peak. These findings suggest that a single peaked posterior tibial nerve P37m consists of partially overlapping two subcomponents generated in area 3b and an area near the marginal sulcus.

Frequency representation in the human hand somatosensory cortex: a reappraisal.

Frequency organization in the human primary somatosensory cortex (SI) was re-examined. Somatosensory evoked magnetic fields (SEFs) were measured with a 37 channel first-order axial gradiometer system. Sensory stimuli comprising a 20ms vibration at frequencies of 50, 100, 200 and 400 Hz were delivered to the volar surface of the tip of the right index finger. Using a single dipole model, the sources of the first main peak (M50) of SEFs were estimated. All of the sources were located in the 3b area. There were no statistically significant differences between the locations of the dipoles evoked by different frequency stimulations. These results support our previous study using a 122 channel whole head planar gradiometer system that systematic frequency organization at the hand area of SI cortex may not be present in humans.

Odorant evoked magnetic fields in humans.

We investigated the olfactory evoked magnetic fields (OEFs) in 14 normal subjects. Pulses of odorant air containing amyl acetate or phenethyl alcohol, and odorless air were administered to the subject through a nasal tube. A clear and consistent OEF component, 1M, was identified in all subjects, and a second component, 2M, was detected in seven subjects, but no consistent component was identified in response to the odorless air. The peak latencies of the 1M and 2M components were approximately 320 and 630 ms, respectively. The waveforms produced by the odorless air were subtracted from the waveforms produced by the odorant air to obtain the 'subtraction' waveform, which indicated the 1M and 2M component more clearly. Their equivalent current dipoles (ECDs) were estimated in the regions around the Sylvian fissure symmetrically in both hemispheres. Therefore, these areas are proposed to be involved in olfactory perception in humans.

Looped device for inferior vena cava taping through a right parasternal approach.

In small adults and infants, inferior vena caval taping through the right parasternal approach for minimally invasive cardiac operations is often difficult with conventional methods. We present a new convenient method to simplify this critical step.

A possible role for BDNF, NT-4 and TrkB in the spinal cord and muscle of rat subjected to mechanical overload, bupivacaine injection and axotomy.

Neurotrophins play a crucial role in the regulation of survival and the maintenance of specific functions for various populations of neurons. Neurotrophin-4 (NT-4) is most abundant in skeletal muscle, and is thought to promote sciatic nerve sprouting, inhibit agrin-induced acetylcholine receptor (AChR) clustering, evoke postsynaptic potentiation and induce mitochondrial proliferation. Using Western blot analysis, immunoprecipitation and immunohistochemistry, we investigated the distribution of NT-4 in slow- and fast-type muscles. We also tested the adaptive response of this protein in the mechanically overloaded muscle, in the regenerating muscle following bupivacaine injection and in the denervated muscle. Additionally, we investigated whether TrkB phosphorylation in the spinal cord and in the sciatic nerve occurs through the interaction with BDNF or NT-4 when the innervating muscle is damaged. Markedly more NT-4 was expressed in fast-type muscles compared with the slow types. TrkB protein was more frequently observed around the edge of myofibers (neuromuscular junction) of the soleus muscle compared with the gastrocnemius muscle. TrkB tyrosine phosphorylation occurred in the spinal cord but not in the sciatic nerve 24 h after bupivacaine injection of the innervating muscle. At the same time, the amount of TrkB co-precipitating with BDNF was markedly increased in the spinal cord. A rapid activation of TrkB (1-8 h) was also observed in the spinal cord after axotomy,while the amount of TrkB co-precipitating with NT-4 was markedly lower after axotomy. These results indicate that NT-4 is preferentially distributed in fast-type muscles. Furthermore, by interacting with BDNF and NT-4, the TrkB in the spinal cord may be important for the survival of motoneurons and outgrowth of injured peripheral axons following muscle damage.

Neural source estimation from a time-frequency component of somatic evoked high-frequency magnetic oscillations to posterior tibial nerve stimulation.

OBJECTIVE: High frequency oscillations (HFOs) evoked by posterior tibial nerve stimulation were recorded using magnetoencephalography (MEG). Time-frequency domain multiple signal classification (TF-MUSIC) algorithm was applied, and the usefulness of this method was demonstrated. METHODS: Ten normal subjects were studied. To localize sources for the HFOs of those somatosensory evoked fields, we applied two kinds of methods: the single moving dipole (SMD) method and the TF-MUSIC method. The SMD method was applied after digitally band-pass filtering the somatosensory response with a bandwidth of 500-800 Hz. To estimate the locations of sources with the TF-MUSIC algorithm, we first set the target region on the spectrogram of the somatosensory responses. Then, the procedure described in Section 2.2 was applied with this target region. RESULTS: A clear, isolated region was detected in 6 out of 10 subjects using a time-frequency spectrogram. The averaged distance of the dipole sources between the HFOs and the underlying P37m using the TF-MUSIC algorithm was smaller than using the SMD method. CONCLUSIONS: The TF-MUSIC algorithm is suitable for extracting a target response whose spectrum changes significantly during the observation.

Reciprocal modulation of somatosensory evoked N20m primary response and high-frequency oscillations by interference stimulation.

OBJECTIVES: We examined whether the inverse relation between somatic evoked N20m primary response and high-frequency oscillations during a wake-sleep cycle (Hashimoto, I., Mashiko, T., Imada, T., Somatic evoked high-frequency magnetic oscillations reflect activity of inhibitory interneurons in the human somatosensory cortex, Electroenceph clin Neurophysiol 1996;100:189-203) holds for interference stimulation. METHODS: Somatosensory evoked fields (SEFs) from 14 subjects were measured following electric median nerve stimulation at the wrist with, and without, concurrent brushing of the palm and fingers. SEFs were recorded with a wide bandpass (0.1-1200 Hz) and then N20m and high-frequency oscillations were separated by subsequent low-pass (< 300 Hz) and high-pass (> 300 Hz) filtering. RESULTS: The N20m decreased dramatically in amplitude during interference stimulation. In contrast, the high-frequency oscillations moderately increased in number of peaks. CONCLUSIONS: These results demonstrate the presence of an inverse relation between N20m and high-frequency oscillations for interference stimulation. We speculate that the high-frequency oscillations represent a localized activity of GABAergic inhibitory interneurons of layer 4, characterized by a high-frequency spike burst (200-1000 Hz) without adaptation, and that the continuous interference stimulation induces tonic excitation of the interneurons, leading to a facilitation of responses to the coherent afferent volley elicited by the median nerve stimulation (bottom-up mechanism). On the other hand, refractoriness of the pyramidal neurons caused directly by interference stimulation along with an enhanced feed-forward inhibition from the interneurons will lead to a decrease of N20m amplitude.

The dynamic processes for word and picture encoding in the human brain as revealed by magnetoencephalography.

Subjects were asked to memorize either the size or the meaning of the first stimulus (encoding) of a stimulus pair, and to match it to the second stimulus. Words and pictures were used as the stimuli in separate tests. Two components named 1M and 2M in both hemispheres for word or picture stimuli could be detected by magnetoencephalography (MEG). The dipole location of 1M in bilateral hemispheres for words is different from that for pictures, but that of 2M is not. It is considered that picture and word are processed in different systems at the initial stage, mainly in the lateral temporal cortex for words and in the parietal cortex for pictures, whereas they are processed in a common semantic system at the late stage.

Dynamic mediolateral activation of the pyramidal cell population in human somatosensory 3b area can be visualized by magnetic recordings.

Dynamic mediolateral activation in the pyramidal cell population of the human somatosensory 3b area was studied non-invasively. Somatosensory evoked fields (SEFs) were recorded over the hand area contralateral to the right median nerve stimulation at the wrist. Localization of an equivalent current dipole (ECD) for N20m primary cortical response was successively calculated for periods of 2.4 ms around N20m peak where the signal-to-noise ratio exceeded 100 and the spatial resolution was approximately 0.3 mm. The ECD moved toward the anterior, lateral and inferior direction for a distance of 8.7 mm at a propagation velocity of 3.6 m/s. This direction was orthogonal to the orientation of apical dendrites of the pyramidal neurons in area 3b and parallel to the surface of the posterior bank of the central sulcus. These findings suggest that the sequential mediolateral activation of the pyramidal cells in the somatosensory cortex is mediated by horizontal connections running parallel to the cortical surface.