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Objective To verify the effects of structured home-based exercises without supervision by a physical therapist in patients with early-stage amyotrophic lateral sclerosis (ALS). Design A historical controlled study that is part of a multicenter collaborative study. Setting Rehabilitation departments at general hospitals and outpatient clinics with a neurology department. Participants Patients (N=21) with ALS were enrolled and designated as the home-based exercise (Home-EX) group, and they performed unsupervised home-based exercises. As a control group, 84 patients with ALS who underwent supervised exercise with a physical therapist for 6 months were extracted from a database of patients with ALS and matched with the Home-EX group in terms of their basic attributes and clinical features. Intervention The Home-EX group was instructed to perform structured home-based exercises without supervision by a physical therapist that consisted of muscle stretching, muscle training, and functional training for 6 months. Main Outcome Measures The primary outcome was the score on the ALS Functional Rating Scale–Revised (ALSFRS-R), which is composed of 3 domains: bulbar function, limb function, and respiratory function. The score ranges from 0 to 48 points, with a higher score indicating better function. Results In the Home-EX group, 15 patients completed the home-based exercises for 6 months, and 6 patients dropped out because of medical reasons or disease progression. No adverse events were reported. The Home-EX group was found to have a significantly higher respiratory function subscore and total score on the ALSFRS-R than the control group at follow-up (P Conclusions Structured home-based exercises without supervision by a physical therapist could be used to alleviate functional deterioration in patients with early-stage ALS.

Isolation and culture of Xenopus laevis neural tubes resulted in differentiation of melanophores and iridophores from neural crest cells; the differentiated melanophores and iridophores were then maintained in culture for more than 6 months. Guanosine has been reported to promote reflecting platelet formation in melanin-producing pigment cells; however, the process of pigment organellogenesis is still unclear. In the present study, unusual light-reflecting pigment cells were observed upon addition of guanosine to the neural tube culture system, which contained melanosomes specific to melanophores, and reflecting platelets specific to iridophores. Ultrastructural studies suggested that irregularly shaped reflecting platelets were formed from stage II melanosomes (the early stage of melanosome formation) in these unusual pigment cells.

Lysine-based amphipathic nonapeptides, including homochiral peptides [Ac-(l-Lys-l-Lys-Xaa)3-NH2 (Xaa=Gly, Ala, Aib, Ac5c, or Ac6c) and Ac-(d-Lys-d-Lys-Aib)3-NH2], a heterochiral peptide [Ac-(l-Lys-d-Lys-Aib)3-NH2], and a racemic mixture of diastereomeric peptides [Ac-(rac-Lys-rac-Lys-Aib)3-NH2] were designed and synthesized to investigate the relationship between their preferred secondary structures and their antimicrobial activity. Peptide 5, [Ac-(l-Lys-l-Lys-Ac6c)3-NH2] formed a stable α-helical structure and exhibited strong activity against Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa).

We reported that cerebellar transcranial magnetic stimulation (TMS) facilitates spinal reflex in healthy humans. The aim of this study was to investigate whether the “cerebellar” spinal facilitation (CSpF) appears in patients with spinocerebellar ataxia (SCA) with atrophy in the cerebellar cortex and dentate nucleus (DN). Two patients with SCA (one was SCA6 and the other was SCA31), participated in this study. Cerebellar inhibition (CBI) was tested using paired-TMS-paradigm with interstimulus intervals (ISI) of 1–8 ms in the right first dorsal interosseous muscle. To measure CSpF, we delivered TMS over the right cerebellum 100–130 ms before right tibial nerve stimulation, and CSpF was calculated with obtained conditioned/unconditioned H-reflex amplitude in the right soleus muscle. Voxel-based morphometry was used to verify the atrophy in cerebellar cortex and the DN. The results showed absence of CBI, but there was a significant facilitation of the H-reflex which occurred in the 120 ms ISI in both patients. These findings indicate that the pathways associated with the induction of CSpF and CBI are different, and that the cerebellar cortex and the DN are not required for inducing CSpF. Possible generator of CSpF could be other deep cerebellar nuclei or the brain stem.

The objective of this research is to realize fully robot-operated farming from tillage to harvest in large-scale agriculture such as cultivation of rice, wheat and soybean in Japan. For this purpose, three types of robot have been developed; the first is robot tractor, the second are rice transplanter robots, the third are combine harvester robots. RTK-GPS and inertia measurement unit (IMU), or GPS compass, are used for navigation system. Robots have Controller Area Network (CAN) bus that all sensors and PC can be connected in common among other robots such as tractors, rice transplanters, and combine harvesters. These robots could be done autonomous operation in paddy field. In addition, moving between the fields for effective operations and safe guideline for robot system were discussed.

In this paper, development and standardization of on-vehicle control and communication data network for small size farm machinery is described. There already exist an international standard and many compliant products in the western countries. But, they are too huge and complicated for the average Japanese style of farming, which is represented by the words of small tractors and small paddy fields. In order to achieve an advancement and cost reduction in this field, enough and sufficient low cost simple electronic devices and related software were developed. The communication method adopted basically depends on the ISO 11783 standard technology, and some new features needed for the domestic agricultural conditions are considered. At the same time, a new domestic simple standard for data exchange between ECU's on tractors and attached implements are discussed. From some experiments, it became clear that the developed hardware and software together are strong tools to realize the domestic standardized devices. It can be said that standardization of data communication for lower range of farm machinery just has been started.

We have developed a new Global Positioning System (GPS) guided rice transplanter. We developed GPS and IMU guided rice transplanter in previous researches. Those were guided with GPS position data and inertia measurement unit (IMU) direction data. New one is guided with GPS position data with tilt correction during straight driving and guided with IMU direction data during turning at the headland. The GPS antenna is set to 1.5m height and 0.4m front offset from vehicle front axle. The actuator control command and data communication protocols comply with through the controller area network (CAN) bus. Steering and transmission are controlled by electrical actuators according to the location in a field. We report results of experiment.

Previously, we established a method to produce recombinant proteins (r-proteins) in cocoons of germline transgenic silkworms, and showed that a step(s) in post-transcription processes was rate-limiting in obtaining a high yield of r-proteins. In this study, we examined whether the 5'-untranslated region (5'-UTR) of the polyhedrin gene (pol) of nucleopolyhedrovirus (NPV) has a translational enhancer activity in the r-protein expression by middle silk gland (MSG) cells of silkworm Bombyx mori (Bm). Sericin 1 gene (ser1) promoter-driven transformation vectors were constructed in which pol5'-UTRs of NPVs isolated from four different species, Bm, Spodoptera frugiperda, Ectropis oblique, and Malacosoma neustria, were each placed upstream of a reporter gene. Transient expression assays in MSGs showed that these pol5'-UTRs all enhanced the protein expression of reporter genes, and the pol5'-UTR of Bm NPV (pol5'-UTR/Bm) was the most effective among them. Thus, transgenic silkworms were generated, which bore the ser1 promoter-driven His-tagged secretory EGFP (sEGFP-His) gene under the control of pol5'-UTR/Bm. The synthesis of sEGFP-His proteins in MSGs of the transgenic worms was approximately 1.5-fold higher than that in those bearing null vectors. However, its mRNA expression levels were 67% of the control worms, indicating that the pol5'-UTR/Bm specifically enhanced the translational level. In conclusion, pol5'-UTR/Bm increased the yield of r-protein production in transgenic silkworms by enhancing the translational activity and this 5'-UTR could be useful for the mass production of r-proteins in germline transgenic silkworms.

The homeobox transcription factor Mtx2 is essential for epiboly, the first morphogenetic movement of gastrulation in zebrafish. Morpholino knockdown of Mtx2 results in stalling of epiboly and lysis due to yolk rupture. However, the mechanism of Mtx2 action is unknown. The role of mtx2 is surprising as most mix/bix family genes are thought to have roles in mesendoderm specification. Using a transgenic sox17-promoter driven EGFP line, we show that Mtx2 is not required for endoderm specification but is required for correct morphogenetic movements of endoderm and axial mesoderm. During normal zebrafish development, mtx2 is expressed at both the blastoderm margin and in the zebrafish equivalent of visceral endoderm, the extra-embryonic yolk syncytial layer (YSL). We show that formation of the YSL is not Mtx2 dependent, but that Mtx2 directs spatial arrangement of YSL nuclei. Furthermore, we demonstrate that Mtx2 knockdown results in loss of the YSL F-actin ring, a microfilament structure previously shown to be necessary for epiboly progression. In summary, we propose that Mtx2 acts within the YSL to regulate morphogenetic movements of both embryonic and extra-embryonic tissues, independently of cell fate specification.

In zebrafish development, Nodal signaling is critical for the induction of endoderm and mesoderm. Three transcription factors downstream of Nodal, Bonnie and Clyde (Bon), Faust (Fau)/Gata5 and Casanova (Cas), are required for endoderm induction. However, it is not yet fully understood how the Nodal signaling pathway regulates the decision process of endoderm and mesoderm induction. In this study, we focused on Fgf signaling, downstream of Nodal signaling, during endoderm induction. We found that activation of Fgf signaling decreases the number of cas-expressing endodermal cells. Conversely, inhibition of this signaling increases the number of endodermal cells without affecting the expression of Nodal, Nodal antagonists, bon or fau/gata5. Inhibition of Fgf signaling in endoderm mutants suggests that this signaling negatively regulates cas expression by a pathway parallel to Bon and Fau/Gata5 in the molecular cascade leading to endoderm. Furthermore, activation of Fgf signaling can overcome Cas-mediated abrogation of mesodermal gene expression. Altogether, these results suggest that Fgf signaling negatively regulates endoderm induction, possibly through repression of cas expression and down-regulation of Cas function.

NCAM in vertebrates and its related molecules, apCAM in Aplysia, fasciclin II in Drosophila, and OCAM in mammals, play key roles in various aspects of brain development and functions. In this study, we have identified and characterized three members of the NCAM gene family in zebrafish, designated as zNCAM, zOCAM, and zPCAM. Three molecules exhibit similar domain organization: an amino-terminal signal peptide, five immunoglobulin-like domains, two fibronectin type III-like domains, a transmembrane segment, and a carboxy-terminal cytoplasmic region. A novel molecule zPCAM is most closely related to zNCAM with 66% amino acid identity. Diversity in the extracellular region of zPCAM is generated by insertion of two different types of variable alternatively spliced exons. In situ hybridization analysis revealed that three molecules were specifically expressed by the central and peripheral nervous systems from early developmental stages in region-specific and cell-type-specific manners. For example, zPCAM showed a neuromere-specific segmental expression pattern, while zOCAM first appeared in specific clusters of secondary neurons in the forebrain. These results suggest that each member of the NCAM gene family plays distinct roles in the formation and maintenance of functional neuronal networks in the zebrafish nervous system.

Zebrafish ten-m3 and ten-m4 encode proteins highly similar to the product of Drosophila pair-rule gene tenm/odd Oz (odz). Their products contain eight epidermal growth factor (EGF)-like repeats that resemble mostly those of the extracellular matrix molecule tenascin. During segmentation period, ten-m3 is expressed in the somites, notochord, pharyngeal arches, and the brain, while expression of ten-m4 is mainly restricted to the brain. In the developing brain, ten-m3 and ten-m4 expression delineates several compartments. Interestingly, ten-m3 and ten-m4 show expression patterns complementary to each other in the developing forebrain and midbrain along both rostrocaudal and dorsoventral axes, depending on developmental stages and locations.

Islet-3 is an LIM/homeodomain protein that is expressed specifically in the eyes and the presumptive tectum in the central nervous system of zebrafish (Danio rerio) embryos. Overexpression of the protein (LIMIsl-3) consisting only of the Islet-3 LIM domains in embryos specifically prevented formation of the optic vesicles; caused abnormal termination of the expression of wnt1, engrailed2, and pax2 in the mesencephalic and metencephalic region between 14 hr and 20 hr postfertilization; and severely impaired morphogenetic movement in this region between 20 hr and 26 hr, which should normally lead to formation of the cerebellar primordium. Such defects were all rescued by simultaneous overexpression of Islet-3, suggesting that LIMIsl-3 acted as a specific dominant-negative variant of Islet-3. These data, combined with the results of mosaic analyses, suggest that Islet-3 is activated by putative LIM-binding cofactors and functions to promote evagination of the optic vesicles and to maintain reciprocal interaction between the mesencephalon and the mesencephalic–metencephalic boundary essential for normal development of this region.

A family of short interspersed repetitive elements (SINEs), designated mermaid, is present in the genomes of fish, amphibian and primates, but absent in the mouse genome. We have demonstrated that the sequences of the mermaid family are highly polymorphic in the zebrafish genome as in the human genome. We have also shown that the mermaid sequence can be used to recover zebrafish specific DNA from zebrafish–mouse cell hybrids by using mermaid -specific oligonucleotides as PCR primers. Thus, the mermaid family serves as a valuable genetic tool for the zebrafish genome mapping.

This study was performed to determine the effects of long-term intravenous infusion on the coronary vasodilating actions of continuous intravenous and bolus intracoronary administration of isosorbide dinitrate (ISDN). With quantitative coronary angiography, the coronary diameter and the vasodilating response to intracoronary ISDN (1 mg) at angiographically normal segments were studied before and after intravenous administration of ISDN, 10 to 60 micrograms/min for 1 hour, 2 days, or 5 days. The vasodilating effects of intravenous ISDN were 72% +/- 13%, 65% +/- 21%, and 6% +/- 11% of the response to intracoronary ISDN in the baseline study in each group. Irrespective of the duration of intravenous infusion, subsequent intracoronary ISDN dilated coronary arteries to extent similar to that observed in each baseline study. In conclusion, significant coronary vasodilating effects of intravenous ISDN were observed after a 2-day infusion, whereas tolerance to the vasodilating effects apparently developed within 5 days of infusion. The vasodilating response to bolus intracoronary ISDN was preserved even when the vasodilating effects of intravenous ISDN were no longer present.

The nucleotide sequence of the upstream region of the bphC gene from Pseudomonas sp. strain KKS102 was determined. Four genes were found in this region. Deduced amino acid sequences of the first, second, third and fourth genes showed significant homology with a large subunit of iron-sulfur protein, a small subunit of iron-sulfur protein, ferredoxin and dihydrodiol dehydrogenase, respectively, from other bacteria which degrade biphenyl/polychlorinated biphenyls, toluene and benzene. E. coli, in which the four genes, bphC and the gene for ferredoxin reductase from benzene degrading bacterium were expressed, was able to produce meta-cleavage compounds from chlorinated biphenyls. These results show that these gene products are functional in both biphenyl and polychlorinated biphenyls degradation.

A hybridoma clone producing a monocional antibody (SC78.H81) against scopolamine was established. The monoclonal antibody was an IgG1 (k) antibody with high affinity (1.6 × 101 M−1 for methylscopolamine). The monoclonal antibody was cross-reactive with methylscopolamine and butylscopolamine, and showed weak cross-reactivity with 6β- and 7β-hydroxyhyoscyamine. The cross-reaction with l -hyoscyamine, atropine, scopine and dl -tropic acid was very weak. A competitive enzyme-linked immunosorbent assay using SC78.H81 was established to quantify scopolamine. The sensitivity of the assay allowed detection of 20 pg assay−1 (0.2 ng ml−1) of scopolamine. The assay was applied to the estimation of scopolamine content in hairy root cultures of a Duboisia hybrid.

The toughening mechanism of rubber-modified nylon is discussed in terms of elastic-plastic analysis of the tensile deformation of a two-dimensional model having five octahedral disc inclusions of rubber, facing each other with the disc-to-disc ligament thickness being kept constant. The rubber inclusion induces yielding of the matrix around it not only in the equatorial direction (perpendicular to the stretching direction), as expected from linear mechanics, but also in the ± 45° and ± 135° directions. At larger strains, the yielded zones expand further and eventually pervade over the whole matrix (strain ≈ 0.3). The massive yielding of the matrix is expected to result in a large amount of energy dissipation, and hence the material would be toughened. By similar analysis on a nylon/void system, the void is shown to play the same role for the toughening; however, it is less effective than rubber. The results suggest that a tougher material will be prepared when the interface between nylon and rubber is more strongly designed so that it is preserved from debonding (which corresponds to a transformation of the nylon/rubber system to the nylon/void system).

The effects of oral diltiazem (90-180 mg/day for four weeks) on ventricular premature contractions (VPCs) were studied in 16 patients with frequent VPCs using 24-hour ambulatory ECG recordings. VPC frequency was evaluated as a function of underlying heart rate. Plots of VPC frequency vs. heart rate were made at 1-beat/min intervals for all heart rates recorded for at least five minutes during 24 hours. Patterns of correlation between VPC frequency and heart rate observed before diltiazem therapy included: 1) a relatively linear increase in VPCs with heart rate (positive correlation) in ten patients, 2) a linear decrease (negative correlation) in one patient, and 3) an increase at low heart rates and a decrease at high heart rates (bidirectional correlation) in five patients. Diltiazem significantly reduced the mean VPC frequency per 24 hours for patients with a positive correlation, but induced no significant change for patients with a negative or a bidirectional correlation. At the 65% level of VPC reduction, diltiazem was effective in eight of ten patients with a positive correlation but was not effective in the six patients with other correlations (p less than 0.01). These results suggest that an evaluation of VPC frequency as a function of heart rate predicts the response of VPCs to diltiazem.

The interaction between the effects of an arterial stenosis and postocclusion hyperemia was studied in a model of the capillaron system. A capillaron is a module consisting of soft-walled permeable vessels (capillaries) in a compliant capsule. Stenosis reduced flow in accord with arterial cross-sectional area. Addition of a capillaron reduced flow to a basal level. In this basal state, autoregulation and postocclusion hyperemia could be studied. Basal flow and autoregulation give no indication of the severity of the stenosis. The magnitude of the postocclusion hyperemia varied with the arterial pressure and, inversely, with the stenotic orifice area. In the absence of arterial pressure changes, the magnitude of the postocclusion hyperemia indicates the severity of the stenosis.

To determine the factors influencing the prognosis of variant angina, the clinical characteristics and long-term prognosis of 158 consecutive Japanese patients were examined and compared with those in previous major western studies (Pisa, Montreal, and Duke studies). The Japanese patients were characterized by relatively low prevalences of coronary risk factors, significant coronary stenoses and previous myocardial infarction. Survival and survival without myocardial infarction for the entire group or for the subpopulation with significant coronary artery disease were significantly better in the Japanese population than in the western populations; however, in the subpopulation without significant coronary artery disease, the prognosis was excellent in all four studies. If the prevalence of coronary artery disease was corrected for the Japanese population, there would be no difference in the prognosis between the Japanese and the western populations. It is concluded: (1) the overall prognosis of variant angina may be better in Japanese patients, and (2) coronary artery disease appears to be the strongest prognostic factor for assessing the differences in the prognosis between the Japanese and the western populations.

To elucidate possible genetic links in the pathogenesis of coronary artery spasm, we investigated the frequencies of human leucocyte antigen in 37 patients with variant angina and 236 unrelated healthy controls. We found no significant differences in human leucocyte antigen frequencies between the patients and the controls. These results may suggest that genetic factors in linkage disequilibrium with human leucocyte antigen may not be involved in the pathogenesis of coronary artery spasm.

To determine the effects of diltiazem, a new calcium antagonist, on myocardial ischemia, two experiments were performed. The results showed 1) the intravenous bolus injection of large doses of diltiazem reduced ST segment elevation in open-chest dogs with acute coronary occlusion. The regional myocardial blood flow in the control area, as well as moderately and mildly ischemic areas increased significantly after diltiazem. However, the myocardial Mood flow of the severely ischemic area did not increase; 2) the continuous infusion of small doses of diltiazem after coronary occlusion for 24 hours caused a significant increase of myocardial blood flow to the circumscribed region at the ischemic center, and induced a tendency to a slight reduction in size of the myocardial infarction.

1. (1) The cerebral arteries of 374 Japanese subjects were estimated for total lipids, free and ester cholesterol, lipid phosphorus, triglycerides and various types of glycosaminoglycans. The cerebral arteries were divided into normal and diseased. The samples were pooled for each decade, in an endeavour to dissociate age changes from those related to atherosclerosis. 2. (2) In general, lipid concentration increased with age and atherosclerosis. The ratio, ester/total cholesterol, in normal tissue was approximately 25–30%, in contrast with 45–50% in the lesions. Atherosclerotic lesions contained approximately 13 to 35 times as much esterified cholesterol as young normal tissue. The rise with age in total and esterified cholesterol in the Japanese cerebral arteries was much the same or just slightly steeper than that reported in South African and American Caucasians. 3. (3) Total glycosaminoglycans increased in both normal tissue and lesions. The proportion and concentration of heparan sulphate decreased in atherosclerosic lesions compared with grossly normal tissue; yet those of chondroitin-4- or -6-sulphate and dermatan sulphate increased. The relative proportions of glycosaminoglycans in normal tissues did not alter with age. 4. (4) Quantitative chemical analysis confirmed the low proportion of both hyaluronic acid and chondroitin sulphates in the total glycosaminoglycans of Japanese cerebral arteries.

We report herein a case with multiple coronary arterioventricular fistulas, in which exercise-induced myocardial ischemia was demonstrated by stress thallium scintigraphy, illustrating the coronary “steal” phenomenon. A 52-year-old Japanese man complained of exertional chest pain for 1 year. The chest pain was relieved by rest but not by sublingual nitroglycerin or oral isosorbide dinitrate. His past medical history and family history were not contributory. Physical examination revealed blood pressure or 100/60 mm Hg and regular heart rate of 80lmin. There was no heart murmur. The chest x-ray examination showed slight cardiac dilation with cardiothoracic ratio of 52 % . The ECG showed T wave inversion in leads II, III, aVr, and V,.,. He complained of chest pain at peak treadmill exercise, along with pseudonormalization of T waves in leads II, III, aVr, and V,.,. Thallium-201 emission computed myocardial tomography at rest showed a mild perfusion defect of the inferoposterior to lateral wall of the left ventricle (LV) and posterior half of the septum, where severe perfusion defect was induced by peak ergometer exercise, with chest pain and pseudonormalization of T waves in leads II, III, aVr, and V,, (Fig. 1). Cardiac catheterization showed normal right and left heart pressures and no evidence of an intracardiac shunt. Left ventriculography revealed normal cavity size and no wall motion abnormality. Selective coronary arteriography showed no stenotic lesions and multiple fistulas from all three major coronary arteries (Fig. 2). The coronary venous drainage was normal. Propranolol therapy was started at oral doses of 90 mg/day and the frequency of exertional angina decreased. Although coronary artery fistula is an unusual congenital anomaly, clinical experiences have accumulated along with the evidence of selective coronary arteriography. However, the majority of coronary artery fistulas drain into the right heart chamber from a single coronary artery. Multiple coronary artery fistulas communicating with the LV involving all three major coronary arteries are extremely rare, and only five cases have been reported in the world literature.‘-5