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Neutrophil extracellular traps (NETs) play important roles in host immunity, as there is increasing evidence of their contribution to the progression of several types of cancers even though their role in colorectal cancers (CRCs) remains unclear. To investigate the clinical relevance of NETs in CRCs, we examined the expression of citrullinated histone H3 using immunohistochemistry and preoperative serum myeloperoxidase–DNA complexes in CRC patients using an enzyme-linked immunosorbent assay. High expression of intratumoral or systemic NETs was found to correlate with poor relapse-free survival (RFS), for which it is an independent prognostic factor. In vitro investigations of CRC cells (HCT116, HT29) revealed that NETs did not affect their proliferation but did promote the migration of CRC cells mediated by neutrophil elastase (NE) released during NETosis to increase extracellular signal-regulated kinase (ERK) activity. In vivo experiments using nude mice (KSN/slc) revealed that NE inhibition suppressed liver metastases in CRC cells, although it did not affect the growth of subcutaneously implanted tumors. Taken together, these results suggest that NET formation correlates with poor prognoses of patients with CRC and that the inhibition of NE could be a potential therapy for CRC metastases.

Atypical ulna fracture (AUF) is relatively rare and is known to be associated with prolonged bisphosphonate (BP) use. The developmental mechanism remains unclear. We report a patient with an AUF associated with BP and severe spinal deformity. The patient was an 85-year-old woman receiving oral alendronate for 8 years without vitamin D supplementation. During regular kitchen work, she needed left upper limb support. She presented with atraumatic pain over the ulna. Radiographs revealed a transverse fracture in the proximal ulna and ulna bowing deformity. Whole-spine standing radiographs showed severe degenerative kyphoscoliosis. The skin induration with pigmentation on her left elbow that suggested prolonged overload and during standing work, coincided exactly with fracture location. This report suggests that ‘direct stress’, with persistent local overload on the proximal ulna, is one of the developmental mechanisms of AUF, in addition to persistent suppression of bone remodelling by prolonged BP use and vitamin D deficiency. Level of Evidence: Level V (Therapeutic)

The use of tension band wiring (TBW) for comminuted olecranon fractures is less recommendable these days. However, some experts preferentially apply TBW to comminuted fractures resulting in favorable outcomes. We here present the surgical technique using TBW with eyelet and absorbable pins for selected comminuted olecranon fractures and review the clinical and radiographic outcomes. Twenty-four surgically treated patients with Colton Group 2C or 2D olecranon fractures in focus on the intermediate fragment (IMF) were enrolled. IMFs were primarily fixed with buried bioabsorbable poly-l-lactic acid pins followed by definitive fixation of the olecranon process with TBW with eyelet. The adequacy of the reconstructed notch was especially estimated by parameters on radiographs using digital imaging software. The average follow-up was 30 months (10 to 86 months). All 24 fractures achieved union, and the maintenance of the articular curvature was confirmed according to statistical analysis on radiographs. The average elbow flexion was 135.1° (range 100° to 145°), and the average elbow extension was − 4.8° (range − 20° to 10°). The mean Mayo Elbow Performance score was 97.3 points (range 80 to 100 points). No cases of pin migration, infection, nerve problem, heterotrophic ossification, or secondary osteoarthritis were observed. For selected comminuted olecranon fractures, TBW with the eyelet pins and biodegradable pins could yield satisfactory clinical and radiographic outcomes.

Mutations of KRAS gene are found in various types of cancer, including colorectal cancer (CRC). Despite intense efforts, no pharmacological approaches are expected to be effective against KRAS-mutant cancers. Macropinocytosis is an evolutionarily conserved actin-dependent endocytic process that internalizes extracellular fluids into large vesicles called macropinosomes. Recent studies have revealed macropinocytosis's important role in metabolic adaptation to nutrient stress in cancer cells harboring KRAS mutations. Here we showed that KRAS-mutant CRC cells enhanced macropinocytosis for tumor growth under nutrient-depleted conditions. We also demonstrated that activation of Rac1 and phosphoinositide 3-kinase were involved in macropinocytosis of KRAS-mutant CRC cells. Furthermore, we found that macropinocytosis was closely correlated with asparagine metabolism. In KRAS-mutant CRC cells engineered with knockdown of asparagine synthetase, macropinocytosis was accelerated under glutamine-depleted condition, and albumin addition could restore the glutamine depletion-induced growth suppression by recovering the intracellular asparagine level. Finally, we discovered that the combination of macropinocytosis inhibition and asparagine depletion dramatically suppressed the tumor growth of KRAS-mutant CRC cells in vivo. These results indicate that dual blockade of macropinocytosis and asparagine bioavailability could be a novel therapeutic strategy for KRAS-mutant cancers.

Few cases of humeral medial epicondyle nonunion develop to symptomatic condition. We report a pediatric case of distally displaced nonunion. At first, the palliative repair surgery was chosen due to irreduciblity of the epicondyle fragment at 10 years old. After 2 years and 3 months wait for maturation of ossification at the trochlea, the definitive surgery consisting of epicondylectomy and ligament reconstruction was performed. This is the first pediatric case of humeral medial epicondyle nonunion with an unossified trochlea which needed a two-staged surgery. We highlight the surgical plan aimed at anatomical ligament reconstruction focusing an isometric point of MCL.

Axial carpal dislocations and perilunate dislocations are two classifications of carpal disruption. Axial dislocations of the wrist usually occur under dorsopalmar compression force in high-energy trauma [1, 2]. They have been classified into two types: axial-radial and axial-ulnar by Garcia-Elias et al. [1, 2]. On the other hand, with regard to perilunate carpal injuries, Mayfield et al. proposed their mechanism as a 4-stage progressive sequence from radial to ulnar [3]. Both injuries have many variant patterns that are difficult to recognize and diagnose and sometimes these 2 injuries occur in combination [1, 2]. This review article describes that in some cases of axial carpal dislocations, the extreme force which extends to the proximal carpal row can lead to additional perilunate injuries [2]. Recently modification of the classification of perilunate injuries has been proposed to include many complicated variants such as reverse ulnar to radial types [4–6], nondislocation of the capitate from the lunate [7], or translunate carpal injuries [8]. We report here a case of 42-year-old patient who sustained a wrist injury resulting in transtriquetral axial ulnar dislocation associated with scapholunate(SL) dissociation. We highlight the mechanism of the rare pattern in connection with the radiographic information.

Methylcobalamin (MeCbl) is a vitamin B12 analog that has some positive effects on peripheral nervous disorders. Although some previous studies revealed the effects of MeCbl on neurons, its effect on the muscle, which is the final target of motoneuron axons, remains to be elucidated. This study aimed to determine the effect of MeCbl on the muscle. We found that MeCbl promoted the proliferation and migration of C2C12 myoblasts in vitro and that these effects are mediated by the Erk1/2 signaling pathway without affecting the activity of the Akt signaling pathway. We also demonstrated that MeCbl inhibits C2C12 cell apoptosis during differentiation. Our results suggest that MeCbl has beneficial effects on the muscle in vitro. MeCbl administration may provide a novel therapeutic approach for muscle injury or degenerating muscle after denervation.

It has been suggested that interleukin-6 (IL-6) plays a key role in the pathogenesis of rheumatoid arthritis (RA), including osteoporosis not only in inflamed joints but also in the whole body. However, previous in vitro studies regarding the effects of IL-6 on osteoblast differentiation are inconsistent. The aim of this study was to examine the effects and signal transduction of IL-6 on osteoblast differentiation in MC3T3-E1 cells and primary murine calvarial osteoblasts. IL-6 and its soluble receptor significantly reduced alkaline phosphatase (ALP) activity, the expression of osteoblastic genes (Runx2, osterix, and osteocalcin), and mineralization in a dose-dependent manner, which indicates negative effects of IL-6 on osteoblast differentiation. Signal transduction studies demonstrated that IL-6 activated not only two major signaling pathways, SHP2/MEK/ERK and JAK/STAT3, but also the SHP2/PI3K/Akt2 signaling pathway. The negative effect of IL-6 on osteoblast differentiation was restored by inhibition of MEK as well as PI3K, while it was enhanced by inhibition of STAT3. Knockdown of MEK2 and Akt2 transfected with siRNA enhanced ALP activity and gene expression of Runx2. These results indicate that IL-6 negatively regulates osteoblast differentiation through SHP2/MEK2/ERK and SHP2/PI3K/Akt2 pathways, while affecting it positively through JAK/STAT3. Inhibition of MEK2 and Akt2 signaling in osteoblasts might be of potential use in the treatment of osteoporosis in RA.

Neuropathic pain caused by nerve damage in the central and/or peripheral nervous systems is a refractory disorder and the management of such chronic pain has become a major issue. Neurotropin is a drug widely used in Japan and China to treat chronic pain. Although Neurotropin has been demonstrated to suppress chronic pain through the descending pain inhibitory system, the mechanism of analgesic action in the peripheral nervous system remains to be elucidated. In this study, we investigated the local effects of Neurotropin on peripheral nerve damage in a chronic constriction injury (CCI) model. Neurotropin reduced mRNA expressions of IL-1β, IL-6, and TNF-α in the sciatic nerve 1 day after the injury. Activation of Erk was also inhibited locally in the Neurotropin treatment group. Since Erk activation results in demyelination along with dedifferentiation of Schwann cells, we investigated the expression level of myelin basic protein. Five days after the injury, Neurotropin attenuated the downregulation of myelin basic protein in the sciatic nerve in the CCI model. Local effects of Neurotropin around the injury site may result in discovery of new treatments for not only neuropathic pain but also demyelinating diseases and peripheral nervous system injury.

Information technology has developed considerably, and this development has resulted in striking changes in the library environment. We should adopt the newly developed electronic networks and make good use of the changes to increase customer satisfaction. We can no longer maintain customer satisfaction at the present level without the support of outsourcing. The feedback system from customers is the most important factor in improving library work.

We newly designed super-elastic biodegradable scaffolds with longitudinally oriented microchannels for repair and regeneration of peripheral nerve defects. Four-armed poly(e-caprolactone-co-D,L-lactide)s (P(CL-co-DLLA)s) were synthesized by ring-opening copolymerization of CL and DLLA from terminal hydroxyl groups of pentaerythritol, and acryloyl chloride was then reacted with the ends of the chains. The end-functionalized P(CL-co-DLLA) was crosslinked in a cylindrical mold in the presence of longitudinally oriented silica fibers as the templates, which were later dissolved by hydrofluoric acid. The elastic moduli of the crosslinked P(CL-co-DLLA)s were controlled between 10−1 and 102 MPa at 37 °C, depending on the composition. The scaffolds could be elongated to 700% of their original size without fracture or damage (‘super-elasticity’). Scanning electron microscopy images revealed that well-defined and highly aligned multiple channels consistent with the mold design were produced in the scaffolds. Owing to their elastic nature, the microchannels in the scaffolds did not collapse when they were bent to 90°. To evaluate the effect of the channel diameter on Schwann cell migration, microchannels were also fabricated in transparent poly(dimethylsiloxane), allowing observation of cell migration. The migration speed increased with channel size, but the Young's modulus of the scaffold decreased as the channel diameter increased. These findings may serve as the basis for designing tissue-engineering scaffolds for nerve regeneration and investigating the effects of the geometrical and dimensional properties on axonal outgrowth.

Methylcobalamin (MeCbl), a vitamin B12 analog, promotes neurite outgrowth by activating Akt in neurons. However, Akt is involved in many cellular functions, and the downstream signal of Akt that promotes neurite outgrowth in neurons in the presence of MeCbl remains obscure. Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that regulates multiple cellular functions including neurite outgrowth. mTOR is regarded as important for the regeneration of injured nerves. In this study, we examined the relationship between MeCbl and mTOR activity and found that MeCbl increases mTOR activity via the activation of Akt and promotes neurite outgrowth in cerebellar granule neurons via the activation of mTOR.

Fur den Prozes der Reform des Bildungswesens ist es unerlaslich, folgende Punkte sorgfaltig zu uberdenken: 1. Erkennen des Status quo und seiner Probleme 2. grundsatzliche Prufung der Probleme 3. Festlegung der Richtung der Reform und ihrer Wertvorstellungen 4. Formulierung konkreter Masnahmen.

Chapitre 1. Le sentiment de la nature et les consequences ethiques, legales et culturellesJe me suis permis de discuter du sujet qui m’a ete donne, a savoir, le sentiment de l’environnement qui nous entoure, ainsi que ses consequences ethiques, juridiques et culturelles.Dans ce contexte, l’environnement est compose du monde naturel, ou la « premiere nature », et la civilisation moderne, nourrie par la science et la technologie et l’economie moderne, que j’appelle la « deuxieme nature ».La discussion au Japon concernant la relation entre nature et etres humains est mentionnee dans la theorie du « Klima » presentee par le Dr Watsuji, professeur de philosophie a l’universite de Kyoto et le Dr Tereda, professeur de physique a l’universite de Tokyo.Les effets de la civilisation moderne et les difficultes qu’elle presente pour les etres humains constituent les problemes les plus graves rencontres par les nations hautement industrialisees d’aujourd’hui.Afin de surmonter les problemes auxquels nous sommes confrontes, j’aimerais recommander que l’on ecoute les opinions des fondateurs de la civilisation moderne.Heureusement, au Japon, nous avons le theâtre traditionnel appele « Noh » par lequel nous pouvons communiquer avec les morts.Ecoutons les opinions du Dr Rene Descartes sur le developpement remarquable de la science et de la technologie ces dernieres annees; du Dr Adam Smith sur la veritable signification de son interet personnel dans son livre, « The Wealth of Nations » et sur l’economie moderne; de Mr Yukichi Fukuzawa au sujet de l’esprit eclaire des japonais qui ont accepte « Yosai », ou la connaissance occidentale, au cours de la Restauration Meiji.

Measurement of Flow velocity distribution around a marine propeller was carried out by Laser Doppler Velocimeter in a cavitation tunnel. The LDV measurement system which can supply both velocity data and measuring position data relative to blade position was developed, and the information about instantaneous velocity distribution around propeller blades was obtained. Authors succeeded in revealing the vortex system around propellre blades. The effects of strong vortex extending from blade tip was found in the measured velocity data. Accelerated and contracted vortex extending from blade tip was found in the measured velocity data. Accelerated and contracted Flow behind blades was also appeared. Thrust and torque estimated from velocity distribution in slip stream ware compared with direct measurement results. Comparison between experimental results and ligting surface theory shows that the existence of strong tip vortex shown by the experiment can not be followed by the theory. It is necessary to investigate the separated Flow in the region near the blade tip, in order to improve the theoretical method.

Recent years have witnessed an wide application of integrated circuits for radio receivers, with use including audio amplifiers, FM/AM IF amplifiers, FM/AM detectors, AM/RF amplifiers, mixers and FM stereo-demodulators. Moreover, a paper (1) describes a single chip AM/FM IC radio in which several of the above-mentioned functions have been integrated into a single chip.

Functions required for the FM radio receiving system including antenna are mainly interference rejection and sensitivity, and are now demanded to be more improved in the face of an increase of FM broadcasting stations.

In the course of study on the dynamic morphology of astrocytes grown in vitro, special attention was paid to the acclimatizing features of processes of astrocytes, to the astrocytes with highly flattened cytoplasm and to the pinocytotic process of unusually large droplets observed in these astrocytes.In the series of mulifarious features observed in the processes of cultured astrocytes, there can be recognized two morphological ‘extremes’; 1. a wide, thin, membrane-like ‘flattened process’, and 2. a fibrous, slender, wire-like ‘condensed process’. Both seem to be highly acclimatized expressions of usual protoplasmic processes to enviromental conditions.The acclimatizing astrocytes with highly flattened processes were named ‘flattened astrocytes’.In the flattened astrocyte, pinocytic granules of unusual size (5-10μ) are occasionally found. These large granules are contacted by several minute phase-dense granules (0.3-1.5μ) with acid phosphatase activity. They may possibly correspond to the microkinetoshere (ROSE 1957a, b) or the lysosome (de DUVE et al. 1955).As a result of interplay between a large pinocytic granule and the minute phasedense granules, there is produced a medium-sized phase-dense granule (2.0-3.5μ). The possible relation of the medium-sized granules to the segresome (TANAKA 1960) or the cytolysome (NOVIKOFF 1959) was discussed.From the information at hand, the pinocytosis in cultured astrocytes per se can not be considered a degenerative process, although it is not an indispensable activity of the cell.

The area of the reticular formation of the brain stem of several newborn and young manmals was cultivated in vitro. Neurons were observed for a period up to 54 days. At the end of this period in many preparations they still exhibited signs of chromatolysis as judged by the eccentric position of the nuclei and the peripheral location of the Nissl material. It has been impossible thus far to identify particular neurons as belonging to a particular nucleus of the reticular formation, probably due to slight morphological and structural changes of these cells in vitro. Although the oldest neurons observed were kept only 54 days in vitro it seems likely that they could have been maintained for a longer time since their appearance indicated more regenerative rather than degenerative features.

Conventional stretch method for elongation test of knitted fabrics does not give accurate data at some points. We have developed new method for it, namely the method by inflation.The tester for new method consists principally of cylinder, thin rubber on upper end of cylinder, pressure gauge, and elongation measure divice. Knitted fabrics are cramped on said rubber and compressed air is sent from compressor to cylinder. Fabrics then are inflated together with rubber by air pressure.This gives similar effect to that of free inflation of knitted fabrics. Therefore, this is proper method for the study of structure of knitted fabrics.The results obtained.1. Elongation of warp knitted fabrics by inflation is given by βk = Ewx Ec, where βk, Ew, Ec are constant, elongation of wale and elongation of course respectively.2. The shape of inflated warp knit fabrics is that of ellipsoid of rotation just as rotated around major axis of wale.3. The shape of inflated weft knit fabrics is that of convex body made by rotating convex curve around longitudinal axis : which curve is drawn when one ellipsoid is put on the other ellipsoid symmetrically : each ellipsoids takes wale and course in major axis.

Generally speaking, the knitted fabrics are deformed by a small force, so the expansive properties of fabrics show properties more precisely than the tensile strength of the knitted fabrics. In order to test them, fabrics are made by different construction and different tensions of warp yarns of warp knitting machine. These specimens are tested by expanding method to obtain the elongation percentage and stresses.The results obtained may be shown by the following equation. αP=Ew2 or αP=Ec2 where Ew: elongation in wale direction Ec: elongation in course direction P: pressure α: factorThe multiplied value of elongation in wale by course direction is constant. The following equation is obtained. Ew•Ec=βK where Ew and Ec are same as given above β:area elongation factor K: orientation factor in specimensThese results show that the properties of fabrics depend more on the properties of the loop rather than on the construction of fabrics and the tension of warp threads.

1. The fate of the embryonal granule cells have been the object of the strenuous study and opinion is still divided. In order to pursue this problem by means of tissue culture, identification was attempted as the first step in this present report.2. The most striking feature of the tissue culture of the cerebellar cortex of the kitten and pnppy younger than 3 weeks after birth is the tremendous migration of the small cells. Among the small cells in the cerebellar cortex of the animals in this stage, the internal granule cells, glial cells and the small cells of the cortex are considered besides the embryonal granule cells.But from the facts as follows the majority of the small cells are considered to belong to the embryonal granular layer.a) The embryonal granule cells which are observed in the cerebellar cortex pressed between the cover glass and slide glass look very much like the small cells migrated in the tissue culture of cerebellar cortex of young animals.b) These small cells do not appear in the tissue culture of the cerebellar cortex of the animals mature enough to lose the embryonal granular layer.c) The small cells which appear in the tissue culture of parts of the brain other than the cerebellar cortex can be identified with the oligodendroglia, immature oligodendroglia and indifferentiated cells. Some of them remain difficult to differentiate from the embryonal granule cells, but this is rather natural considering the entity of the embryonal granule cells.d) The embryonal granule cells seen in the tissue culture correspond well to the cells which have been reported so far by several authors in silver impregnated preparations.3. Discussion was made about the differentiation of the small cells from the oligodendroglia and other indifferentiated cells. Mention was made also on the internal granule cells cultivated in vitro.

Test results on a free running model of a gigantic ore-carrier are described, in which the hydrodynamic pressures on the hull in oblique waves together with the ship behaviors were measured in order to present the useful materials for the method of wave loads estimation. The behavior of the gigantic ore-carrier in rough seas, namely speed loss, ship motions and relative water elevations are shown. The distributions of hydrodynamic pressure amplitudes are shown for various wave length and heading angle. In addition to amplitude distributions, phase relations of the hydrodynamic pressures are also shown. Characteristics of the hydrodynamic pressures are explained in connection with the relative water elevations. Comparison between the experimental data and the calculated results obtained by the strip method are made and the usefulness of the strip method for the estimation of the hydrodynamic pressures is discussed.

Based on the normal histological findings and the organization of the spinal afferents revealed by the Nauta and the Marchi methods, a cell group corresponding to the lateral cervical nucleus (NCL) of the cat was identified in the first and the second cervical segments of the spinal cord of the Japanese monkey (Macaca fuscata). The nucleus begins to appear at the level of the caudal end of the gracile nucleus and gradually disappears within the caudal half of the second cervical segment of the cord. The nucleus consists of medium-sized and small-sized nerve cells and receives spinal afferents ascending through the lateral funiculus, probably chiefly through the posterior spino-cerebellar tract, from lower levels of the spinal cord. The spinal afferents seem to take origin entirely, or at least chiefly, from the ipsilateral spinal gray and to terminate in the nucleus without any localization. Some problems concerning the lateral cervical nucleus as the site of the spino-thalamic tract have also been discussed from the point of view of comparative anatomy.

This paper describes the results of a model test on the impulsive water pressures acting on the hull surface of a gigantic ore-carrier in waves. In order to generate impulsive water pressures on the free running model, especially on the ship side, the regular waves from two directions were adopted as the wave environment of the experiment. From analysis of the test results, it is discussed what parameters affect occurrence of impulsive water pressures and on what part of the hull surface impulsive water pressures will appear. A new measuring system including a special pressure transducer and recording apparatus was prepared. The system worked well to catch impulsive water pressures even in detail of the peak.