Showing papers by "Hirosaki University published in 2004"
TL;DR: In this article, the authors identify retinoic acid inducible gene I (RIG-I), which encodes a DExD/H box RNA helicase that contains a caspase recruitment domain, as an essential regulator for dsRNA-induced signaling.
Abstract: Intracellular double-stranded RNA (dsRNA) is a chief sign of replication for many viruses. Host mechanisms detect the dsRNA and initiate antiviral responses. In this report, we identify retinoic acid inducible gene I (RIG-I), which encodes a DExD/H box RNA helicase that contains a caspase recruitment domain, as an essential regulator for dsRNA-induced signaling, as assessed by functional screening and assays. A helicase domain with intact ATPase activity was responsible for the dsRNA-mediated signaling. The caspase recruitment domain transmitted 'downstream' signals, resulting in the activation of transcription factors NF-kappaB and IRF-3. Subsequent gene activation by these factors induced antiviral functions, including type I interferon production. Thus, RIG-I is key in the detection and subsequent eradication of the replicating viral genomes.
3,775 citations
TL;DR: A new gene is described in this region, EFHC1, which encodes a protein with an EF-hand motif that is associated with juvenile myoclonic epilepsy and which increased R-type Ca2+ currents that were reversed by the mutations associated with JME.
Abstract: Juvenile myoclonic epilepsy (JME) is the most frequent cause of hereditary grand mal seizures. We previously mapped and narrowed a region associated with JME on chromosome 6p12-p11 (EJM1). Here, we describe a new gene in this region, EFHC1, which encodes a protein with an EF-hand motif. Mutation analyses identified five missense mutations in EFHC1 that cosegregated with epilepsy or EEG polyspike wave in affected members of six unrelated families with JME and did not occur in 382 control individuals. Overexpression of EFHC1 in mouse hippocampal primary culture neurons induced apoptosis that was significantly lowered by the mutations. Apoptosis was specifically suppressed by SNX-482, an antagonist of R-type voltage-dependent Ca(2+) channel (Ca(v)2.3). EFHC1 and Ca(v)2.3 immunomaterials overlapped in mouse brain, and EFHC1 coimmunoprecipitated with the Ca(v)2.3 C terminus. In patch-clamp analysis, EFHC1 specifically increased R-type Ca(2+) currents that were reversed by the mutations associated with JME.
326 citations
TL;DR: Changing lipid profiles that reflect atherosclerotic disease led to activation of skin murine dendritic cells locally, promoted dermal inflammation, and induced lymph node hypertrophy, and paradoxically, DC migration to lymph nodes was impaired, suppressing immunologic priming.
256 citations
TL;DR: A novel mechanism for the MU-mediated inhibition of HA synthesis involving the glucuronidation of MU by endogenous UGT resulting in a depletion of UDP-GlcUA is proposed.
249 citations
TL;DR: The results suggest that AMPK inhibits the activation of NF-kappaB caused by both palmitate and TNF-alpha, and its relevance to the reported anti-atherogenic actions of exercise, metformin, thiazolidinediones, and adiponectin, all of which have been shown to activate AMPK, remains to be determined.
232 citations
TL;DR: The results indicate that switching from GABAergic to glycinergic inputs to the LSO may occur at the level of a single presynaptic terminal, demonstrating a new form of developmental plasticity at a single central synapse.
Abstract: Early in postnatal development, inhibitory inputs to rat lateral superior olive (LSO) neurons change from releasing predominantly GABA to releasing predominantly glycine into the synapse. Here we show that spontaneous miniature inhibitory postsynaptic currents (mIPSCs) also change from GABAergic to glycinergic over the first two postnatal weeks. Many 'mixed' mIPSCs, resulting from co-release of glycine and GABA from the same vesicles, are seen during this transition. Immunohistochemistry showed that a large number of terminals contained both GABA and glycine at postnatal day 8 (P8). By P14, both the content of GABA in these mixed terminals and the contribution of GABA to the mixed mIPSCs had decreased. The content of glycine in terminals increased over the same period. Our results indicate that switching from GABAergic to glycinergic inputs to the LSO may occur at the level of a single presynaptic terminal. This demonstrates a new form of developmental plasticity at the level of a single central synapse.
226 citations
TL;DR: The ConPred II system is a server for the prediction of transmembrane (TM) topology based on a consensus approach by combining the results of several proposed methods and will return the predicted TM topology models and graphical representations of their contents.
Abstract: ConPred II (http://bioinfo.si.hirosaki-u.ac.jp/~ConPred2/) is a server for the prediction of transmembrane (TM) topology [i.e. the number of TM segments (TMSs), TMS positions and N-tail location] based on a consensus approach by combining the results of several proposed methods. The ConPred II system is constructed from ConPred_elite and ConPred_all (previously named ConPred), proposed earlier by our group. The prediction accuracy of ConPred_elite is almost 100%, which is achieved by sacrificing the prediction coverage (20-30%). ConPred_all predicts TM topologies for all the input sequences with accuracies improved by up to 11% over individual proposed methods. In the ConPred II system, the TM topology prediction of input TM protein sequences is executed following a two-step process: (i) input sequences are first run through the ConPred_elite program; (ii) sequences for which ConPred_elite does not give the TM topology are delivered to the ConPred_all program for TM topology prediction. Users can get access to the ConPred II system automatically by submitting sequences to the server. The ConPred II server will return the predicted TM topology models and graphical representations of their contents (hydropathy plots, helical wheel diagrams of predicted TMSs and snake-like diagrams).
207 citations
TL;DR: The aim of this study was to delineate the genetic correlation between core SMEI and SMEB and to estimate the frequency of mutations in both phenotypes.
Abstract: Summary: Purpose: Severe myoclonic epilepsy in infancy (SMEI) is a distinct epilepsy syndrome. Patients with borderline SMEI (SMEB) are a subgroup with clinical features similar to those of core SMEI but are not necessarily consistent with the accepted diagnostic criteria for core SMEI. The aim of this study was to delineate the genetic correlation between core SMEI and SMEB and to estimate the frequency of mutations in both phenotypes.
Methods: We examined 96 healthy volunteers and 58 unrelated individuals whose clinical features were consistent with either core SMEI (n = 31) or SMEB (n = 27). We screened for genetic abnormalities within exons and their flanking introns of the genes encoding major subunits of the Na+ channels (SCN1A, SCN2A, SCN1B, and SCN2B) by using a direct sequencing method.
Results: In both core SMEI and SMEB, various mutations of SCN1A including nonsense and missense mutations were identified, whereas no mutations of SCN2A, SCN1B, and SCN2B were found within the regions examined. All mutations were heterozygous and not found in 192 control chromosomes. Mutations were identified in 26 (44.8%) of the 58 individuals and were more frequent (p < 0.05) in core SMEI (19 of 31) than in SMEB (seven of 27), as assessed by the continuity-adjusted χ2 test. Mutations resulting in a molecular truncation were found only in core SMEI. Among the mutations, two missense mutations were found in both core SMEI and SMEB.
Conclusions: Our findings confirm that SMEB is part of the SMEI spectrum and may expand the recognition of SMEI and suggest other responsible or modifying genes.
195 citations
TL;DR: The results suggest that freeze-drying could be applied to preserve the spermatozoa from most other species, including human, and raises the question of whether rabbit sperm centrosomes survive freeze-Drying or are not essential for embryonic development.
Abstract: To date, the laboratory mouse is the only mammal in which freeze-dried spermatozoa have been shown to support full-term development after microinjection into oocytes. Because spermatozoa in mice, unlike in most other mammals, do not contribute centrosomes to zygotes, it is still unknown whether freeze-dried spermatozoa in other mammals are fertile. Rabbit sperm was selected as a model because of its similarity to human sperm (considering the centrosome inheritance pattern). Freezedrying induces rabbit spermatozoa to undergo dramatic changes, such as immobilization, membrane breaking, and tail fragmentation. Even when considered to be ‘‘dead’’ in the conventional sense, rabbit spermatozoa freeze-dried and stored at ambient temperature for more than 2 yr still have capability comparable to that of fresh spermatozoa to support preimplantation development after injection into oocytes followed by activation. A rabbit kit derived from a freeze-dried spermatozoon was born after transferring 230 sperm-injected oocytes into eight recipients. The results suggest that freeze-drying could be applied to preserve the spermatozoa from most other species, including human. The present study also raises the question of whether rabbit sperm centrosomes survive freeze-drying or are not essential for embryonic development. fertilization, in vitro fertilization, oocyte development, sperm
180 citations
TL;DR: The results of the present study suggest that decreased reproduction ability after general load is not due to the loss of peripheral afferent signals, but to other factors, especially deficiency of central processing of proprioceptive signals.
Abstract: Purpose: The purpose of this study was to compare the effects of local and general fatigue loads on knee proprioception Type of Study: Experimental controlled study. Methods: Proprioception of the knee joint was evaluated by measuring absolute angular error (AAE) at matching defined index angles before and after 2 different types of fatigue protocols (local load and general load) in 27 healthy male volunteers. Local load was provided with maximum isokinetic knee flexion-extension on the isokinetic dynamometer, and general load was 5 minutes running on a treadmill. Results: After local load, a significant decrease in peak torque of knee flexors and extensors was found, but no significant change in AAE was seen. In contrast, after general load, a significant increase of AAE was noted without significant muscle weakness. Conclusions: The different results in previous studies evaluating the effect of fatigue on knee proprioception may have been affected by the difference of fatigue protocols, whether local or general load. Although local load was intended to produce local fatigue of the knee, which may cause dysfunction of muscle mechanoreceptors, general load may have produced general fatigue and affected other mechanisms in the proprioceptional pathway. The results of the present study suggest that decreased reproduction ability after general load is not due to the loss of peripheral afferent signals, but to other factors, especially deficiency of central processing of proprioceptive signals. Clinical Relevance: To prevent knee injury caused by fatigue-induced proprioceptional decline, muscle endurance training alone is not enough, and neuromuscular training, including central motor programming, is essential.
178 citations
TL;DR: High-resolution high-energy photoemission spectra together with parameter-free LDA + DMFT (local density approximation + dynamical mean-field theory) results for Sr1-xCaxVO3, a prototype 3d(1) system are reported.
Abstract: We report high-resolution high-energy photoemission spectra together with parameter-free $\mathrm{L}\mathrm{D}\mathrm{A}+\mathrm{D}\mathrm{M}\mathrm{F}\mathrm{T}$ (local density approximation $+$ dynamical mean-field theory) results for ${\mathrm{S}\mathrm{r}}_{1\ensuremath{-}x}{\mathrm{C}\mathrm{a}}_{x}{\mathrm{V}\mathrm{O}}_{3}$, a prototype $3{d}^{1}$ system. In contrast to earlier investigations the bulk spectra are found to be insensitive to $x$. The good agreement between experiment and theory confirms the bulk sensitivity of the high-energy photoemission spectra.
TL;DR: In this paper, the authors investigated the source of the observed deformation as contemporary interplate coupling on the east subducting boundary to the Pacific Plate and the west collision boundary to Amurian Plate.
Abstract: SUMMARY
Temporal change of deformation in northeastern Japan is clarified by continuous Global Positioning System (GPS) observations from 1995 April to 2002 March. The observed GPS velocity is approximately parallel to the direction of plate convergence on east and west plate boundaries of northeastern Japan and shows post-seismic transient deformation around source regions of the Mw 7.8 1993 Hokkaido-Nansei-Oki and the Mw 7.7 1994 Sanriku-Haruka-Oki earthquakes. We interpret the source of the observed deformation as contemporary interplate coupling on the east subducting boundary to the Pacific Plate and the west collision boundary to the Amurian Plate. Using elastic dislocation theory, we inverted horizontal and vertical velocities of 212 GPS stations to estimate interplate coupling on both boundaries. The estimated coupling during 1995–2002 is spatially heterogeneous, however, it is temporally almost constant except for the region around the 1993 and 1994 earthquakes. After-slip of the 1994 earthquake occurred over the coseismic rupture area and its downdip extension on the plate boundary for 0.3–1.3 yr after the earthquake. After-slip continued only in the downdip extension for later periods and decayed with time. Weak coupling was recovered in the eastern part of the coseismic rupture area 3.3 yr after the earthquake. Interplate coupling on the Pacific Plate was strong in two regions, Miyagi-Oki and Tokachi-Oki. The west plate boundary is tightly coupled except for the source areas of three large earthquakes that occurred in 1964, 1983 and 1993. The apparent decoupling of the source areas of these earthquakes implies long-term post-seismic deformation as a result of viscoelastic relaxation in the subseismogenic lithosphere.
TL;DR: Fractalkine plays an important role in the interaction between leukocytes and endothelial cells and is inhibited by the soluble form of IL-6 receptor-alpha, 15-deoxy-Delta(12,14)-prostaglandin J(2), and hypoxia.
Abstract: CX3CL1/fractalkine is a chemokine with a unique CX3C motif. Fractalkine is synthesized in endothelial cells as a membrane protein, and the N-terminal domain containing a CX3C motif is cleaved and secreted. CX3CR1, the specific receptor for fractalkine, is expressed in monocytes and lymphocytes. Membrane-bound fractalkine works as an adhesion molecule for these leukocytes and the secreted form as a chemotactic factor. Fractalkine is produced by endothelial cells stimulated with tumor necrosis factor-alpha, interleukin-1 (IL-1), lipopolysaccharide and interferon-gamma. Expression of fractalkine in endothelial cells is inhibited by the soluble form of IL-6 receptor-alpha, 15-deoxy-Delta(12,14)-prostaglandin J(2), and hypoxia. The expression of fractalkine is tightly regulated and fractalkine plays an important role in the interaction between leukocytes and endothelial cells.
TL;DR: It is demonstrated that naturally occurring PTGS plays a key role in expression of a distinctive phenotype in plants and is presented as a simple clear example of the elucidation of the molecular mechanism for viral symptom induction.
Abstract: Most commercial Glycine max (soybean) varieties have yellow seeds because of loss of pigmentation in the seed coat. It has been suggested that inhibition of seed coat pigmentation in yellow G. max may be controlled by homology-dependent silencing of chalcone synthase (CHS) genes. Our analysis of CHS mRNA and short-interfering RNAs provide clear evidence that the inhibition of seed coat pigmentation in yellow G. max results from posttranscriptional rather than transcriptional silencing of the CHS genes. Furthermore, we show that mottling symptoms present on the seed coat of G. max plants infected with some viruses can be caused by suppression of CHS posttranscriptional gene silencing (PTGS) by a viral silencing suppressor protein. These results demonstrate that naturally occurring PTGS plays a key role in expression of a distinctive phenotype in plants and present a simple clear example of the elucidation of the molecular mechanism for viral symptom induction.
TL;DR: There was a significant phenotype-genotype relationship in generalized epilepsy with febrile seizures plus and severe myoclonic epilepsy of infancy with SCN1A missense mutations, suggesting more severe sodium channel dysfunctions including abnormal ion selectivity that are caused by mutations in the pore regions may be involved in the pathogenesis of SMEI.
Abstract: Background and Methods: Many missense mutations in the voltage-gated sodium channel subunit gene SCN1A were identified in patients with generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI), although GEFS+ is distinct from SMEI in terms of clinical symptoms, severity, prognosis, and responses to antiepileptic drugs. The authors analyzed the localization of missense mutations in SCN1A identified in patients with GEFS+ and SMEI to clarify the phenotype-genotype relationships. Results: Mutations in SMEI occurred more frequently in the “pore” regions of SCN1A than did those in GEFS+. These SMEI mutations in the “pore” regions were more strongly associated than mutations in other regions with the presence of ataxia and tendency to early onset of disease. The possibility of participation of ion selectivity dysfunction of the channel in the pathogenesis of SMEI was suggested by a mutation in the pore region (R946C) identified in a SMEI patient. Conclusions: There was a significant phenotype-genotype relationship in generalized epilepsy with febrile seizures plus and severe myoclonic epilepsy of infancy with SCN1A missense mutations. More severe sodium channel dysfunctions including abnormal ion selectivity that are caused by mutations in the pore regions may be involved in the pathogenesis of SMEI.
07 Jun 2004
TL;DR: A new control method is introduced, which modified the model-based teleoperation system, to control the real robotic system Engineering Test Satellite VII manipulator and shows that the MS approach is the best control method for contact tasks in which the directions of motion of the slave arm and of the operator's input force are different, as in the surface-tracking task.
Abstract: In our previous research, we developed space robot teleoperation technology to achieve control from the ground of effective manual manipulations in orbit. To solve the communication time delay in the space robot teleoperation, we propose a mixed force and motion command-based space robot teleoperation system that is a model-based teleoperation. Moreover, we have also developed a compact 6-degree-of-freedom haptic interface as a master device. The important features of our teleoperation system are its robustness against modeling errors and its ability to realize the force exerted by the operator at the remote site. We introduce a new control method, which modified our model-based teleoperation system, to control the real robotic system Engineering Test Satellite VII manipulator. Surface-tracking and peg-in-hole tasks have been performed to confirm the effectiveness of our system. The experimental results obtained with our system including the haptic interface demonstrate its ability to perform these tasks in space without any major problems. We also evaluated different master device approaches for the model-based space teleoperation system. For this purpose, we used two methods, which are a master-slave (MS) approach and a force-joystick approach. Our results show that the MS approach is the best control method for contact tasks in which the directions of motion of the slave arm and of the operator's input force are different, as in the surface-tracking task.
TL;DR: Nicorandil improves cardiac function and clinical outcomes in patients with AMI and suppression of ROS formation may be involved in the mechanism.
TL;DR: The addition of low intensity exercise to the rest period did not adversely affect physiological recovery and had a significantly beneficial effect on psychological recovery by enhancing relaxation.
Abstract: Background: The psychological and physiological condition of athletes affect both their performance in competitions and their health. Rugby is an intense sport which appears to impose psychological and physiological stress on players. However, there have been few studies of the most appropriate resting techniques to deliver effective recovery from a match.
Objectives: To compare the difference in recovery after a match using resting techniques with or without exercise.
Methods: Fifteen Japanese college rugby football players were studied. Seven performed only normal daily activities and eight performed additional low intensity exercise during the post-match rest period. Players were examined just before and immediately after the match and one and two days after the match. Blood biochemistry and two neutrophil functions, phagocytic activity and oxidative burst, were measured to assess physiological condition, and the profile of mood states (POMS) scores were examined to evaluate psychological condition.
Results: Immediately after the match, muscle damage, decreases in neutrophil functions, and mental fatigue were observed in both groups. Muscle damage and neutrophil functions recovered with time almost equally in the two groups, but the POMS scores were significantly decreased only in subjects in the low intensity exercise group.
Conclusions: Rugby matches impose both physiological and psychological stress on players. The addition of low intensity exercise to the rest period did not adversely affect physiological recovery and had a significantly beneficial effect on psychological recovery by enhancing relaxation.
TL;DR: To reduce the overall mortality rate and to prolong life expectancy in Japan, measures must be taken to reduce those mortality rates associated with seasonal differences, especially those causes of death which show a strong correlation with seasonal change: respiratory, heart, cerebrovascular, diabetes and infectious diseases.
Abstract: Background: It is well recognized that the season of the year exerts an influence on some diseases and causes of death such as coronary heart diseases, stroke, infectious diseases and so on. Methods: We evaluated the influence of seasonal changes on diseases and causes of death in Japan using the Japan Vital Statistics from 1970 to 1999 and recorded weather data (mean temperature), by a Fourier decomposition in a log linear regression model.Results: Major influences of seasonal change with the highest rates in winter were seen on the following: the overall causes of death; infectious and parasitic diseases including tuberculosis; respiratory disease, including pneumonia and influenza; heart and cerebrovascular diseases; diabetes; and digestive diseases and accidents. Two peaks were seen in suicides, a large peak in April and a small peak in autumn. Cancer and homicides were little or not at all influenced by seasonality. There was no major difference in changes between the years studied, except for respiratory disease and tuberculosis, which showed a clear reduction in the seasonality effect from 1970 to 1999. Conclusions: To reduce the overall mortality rate and to prolong life expectancy in Japan, measures must be taken to reduce those mortality rates associated with seasonal differences, especially those causes of death which show a strong correlation with seasonal change: respiratory, heart, cerebrovascular, diabetes and infectious diseases.
TL;DR: The widespread accumulation of phosphorylated α-synuclein in both glial and neuronal cells is a pathological feature in patients suffering from MSA.
Abstract: We immunohistochemically examined the brain and peripheral sympathetic ganglia from eight patients with multiple system atrophy (MSA), using an antibody specific for phosphorylated alpha-synuclein (anti-PSer129). Phosphorylated alpha-synuclein was deposited in five cellular locations: oligodendroglial cytoplasm and nucleus, and neuronal cytoplasm, processes and nucleus. Many neuronal cytoplasmic inclusions (NCIs) were found in the pontine and inferior olivary nuclei and, to a lesser extent, in the substantia nigra, locus ceruleus, and neocortical and hippocampal neurons. NCIs were also found in the sympathetic ganglia in two out of the eight cases. Moreover, anti-PSer129 immunohistochemistry revealed extensive neuropil pathology; swollen neurites were abundant in the pontine nucleus, delicate neurites were observed in the deeper layers of the cerebral cortex and thalamus, and neuropil threads and dot-like structures were distributed in the basal ganglia and brainstem. Diffuse neuronal cytoplasmic staining (pre-NCI) was frequently found in the pontine and inferior olivary nuclei. Thus, the widespread accumulation of phosphorylated alpha-synuclein in both glial and neuronal cells is a pathological feature in patients suffering from MSA.
TL;DR: The registry system in Japan revealed a new clinical situation in FAP patients, and the findings of this study will be useful to improve the prognosis of patients with FAP.
Abstract: The clinical situation of familial adenomatous polyposis (FAP) in Japan has changed in the period since the last analysis of data of the Japanese Polyposis Center. To reevaluate our data and elucidate the changes we analyzed the records of the 1390 FAP patients in 900 families registered with the Polyposis Committee of the Japanese Society for Cancer of the Colon and Rectum. In the 13-year period 1990–2003, clinical differences between men and women with FAP diminished. The postoperative prognosis was substantially better in patients without advanced colorectal cancer (stage ≧ T2) than in those with early cancer or no cancer. Mean age at death improved from 42.5 years in the period before 1990 to 46.0 years, and it was a result of a decreased proportion of deaths from colorectal cancer. The distribution of colorectal cancer in FAP patients was similar to that in the general population. Desmoid tumors accounted for about 10% of deaths in the recent 13 years (1990–2003). The cumulative risk of rectal cancer in the preserved rectum was 12% at 10 years and 23% at 15 years. The registry system in Japan revealed a new clinical situation in FAP patients, and the findings of this study will be useful to improve the prognosis of patients with FAP.
TL;DR: RsgA is a novel GTPase that might provide a new insight into the function of ribosome that was inhibited by several aminoglycosides bound at the A site of the small subunit, but not by a P site-specific antibiotic.
Abstract: The GTPase activity of Escherichia coli YjeQ, here named RsgA (ribosome small subunit-dependent GTPase A), has been shown to be significantly enhanced by ribosome or its small subunit. The enhancement of GTPase activity was inhibited by several aminoglycosides bound at the A site of the small subunit, but not by a P site-specific antibiotic. RsgA stably bound the small subunit in the presence of GDPNP, but not in the presence of GTP or GDP, to dissociate ribosome into subunits. Disruption of the gene for RsgA from the genome affected the growth of the cells, which predominantly contained the dissociated subunits having only a weak activation activity of RsgA. We also found that 17S RNA, a putative precursor of 16S rRNA, was contained in the small subunit of the ribosome from the RsgA-deletion strain. RsgA is a novel GTPase that might provide a new insight into the function of ribosome.
TL;DR: In this article, the effects of N-cadherin expression on invasion and metastasis in vitro and in vivo, were studied in a rat C6 glioma cell line.
Abstract: Cadherins are Ca2+-dependent cell adhesion molecules that play an important role in tissue construction and morphogenesis in multicellular organisms. Over the last few years, reports have emerged in the literature describing the involvement of cadherins in tumor invasion and metastasis. Cadherins typically demonstrate up and down-regulation according to the biological needs of the tissue. Additionally, up-regulation of N-cadherin is thought to be important for tumor formation in early stages of tumor development. We studied N-cadherin in surgical specimens of patients with primary glioblastoma by microarray analysis and found that N-cadherin mRNA expression is up-regulated compared to normal brain. To study the effects of N-cadherin expression on invasion and metastasis in vitro and in vivo, we overexpressed N-cadherin in the rat C6 glioma cell line which normally has low levels of N-cadherin. We found that up-regulation of N-cadherin resulted in a slight decreased adhesion to type IV collagen, fibronectin, and laminin, but statistically significant decreased adhesion to type I collagen. Furthermore, increased expression of N-cadherin correlated with a dramatic decrease in invasive behavior in extracellular matrix invasion assays. We then proceeded to study these cell lines in vivo in a rat intracranial glioma model, and found that N-cadherin expression inversely correlated with invasion into surrounding tissues, irregular margins, and extracranial invasion. In summary, these data collectively demonstrate that N-cadherin levels are important in the malignant behavior of gliomas, and may serve as a prognostic indicator for patients with high-grade gliomas.
TL;DR: Findings suggest that NCI formation is accelerated by the progression of the disease process, and that in MSA, NNI formation is an earlier phenomenon thanNCI formation.
Abstract: Multiple system atrophy (MSA) is a sporadic neurodegenerative disease characterized by the presence of neuronal and oligodendroglial alpha-synuclein aggregates. To investigate the relationship between the occurrence of neuronal cytoplasmic and intranuclear inclusions (NCIs and NNIs, respectively) and the progression of neuronal degeneration, we performed a quantitative analysis of the pontine and inferior olivary nuclei based on 14 cases of MSA. alpha-Synuclein immunohistochemistry revealed that NCIs and NNIs were present in both brain nuclei in all the cases. The average incidence of NCIs in the pontine and inferior olivary nuclei was 9.1% and 25.8%, respectively, and that of NNIs was 9.2% and 9.0%, respectively. The number of NNIs was strongly correlated with that of neurones in the pontine and inferior olivary nuclei. Although the number of NCIs was not correlated with the neuronal population in both nuclei, the NCI count in patients with moderate MSA was higher than in patients with mild MSA. The NNI count was much higher than the NCI count in the pontine nucleus in four patients, and was the same in the olivary nucleus in three of the four patients. Moreover, the neuronal population in the NNI-predominant cases was significantly higher than in the NCI-predominant cases. These findings suggest that NCI formation is accelerated by the progression of the disease process, and that in MSA, NNI formation is an earlier phenomenon than NCI formation.
TL;DR: Biochemical studies demonstrated the impairment of γ-aminobutyric acid (GABA) release because of the reduction of vesicular GABA transporter in μ3B−/− mice, which facilitated the induction of long-term potentiation in the hippocampus and the abnormal propagation of neuronal excitability via the temporoammonic pathway.
Abstract: AP-3 is a member of the adaptor protein (AP) complex family that regulates the vesicular transport of cargo proteins in the secretory and endocytic pathways. There are two isoforms of AP-3: the ubiquitously expressed AP-3A and the neuron-specific AP-3B. Although the physiological role of AP-3A has recently been elucidated, that of AP-3B remains unsolved. To address this question, we generated mice lacking μ3B, a subunit of AP-3B. μ3B−/− mice suffered from spontaneous epileptic seizures. Morphological abnormalities were observed at synapses in these mice. Biochemical studies demonstrated the impairment of γ-aminobutyric acid (GABA) release because of, at least in part, the reduction of vesicular GABA transporter in μ3B−/− mice. This facilitated the induction of long-term potentiation in the hippocampus and the abnormal propagation of neuronal excitability via the temporoammonic pathway. Thus, AP-3B plays a critical role in the normal formation and function of a subset of synaptic vesicles. This work adds a new aspect to the pathogenesis of epilepsy.
TL;DR: The use of an arthroscope during treatment of malleolar fractures enables diagnosis and treatment of the lesions within the ankle joint, producing a satisfactory surgical outcome.
Abstract: Purpose Malleolar fractures have been reported to be associated with a poor prognosis even when the anatomic reduction is complete. Soft tissue injuries such as damage to the cartilage and ligaments, soft tissue impingement, and the existence of free bodies within the intra-articular space account for this poor outcome. In treating fresh malleolar fractures, an arthroscope is used at our institution to confirm anatomic reduction on the articular surface and treat intra-articular injuries. This study evaluated the arthroscopic findings and surgical outcome for fresh malleolar fractures. Type of study Prospective case study. Methods The subjects were 105 patients (105 joints) who had experienced malleolar fractures and had undergone surgical fixation between January 1996 and May 1999. Arthroscopy was used to confirm the fracture line, cartilaginous damage, presence of detached cartilaginous fragments in the articular space, ligament damage, and diastasis of the distal tibiofibular joint. The cartilaginous damage was treated using shaving, and the free cartilaginous fragments were excised. Diastasis of the distal tibiofibular joint was treated using distal tibiofibular joint fixation, using a screw. Fracture fixation was conducted after anatomic reduction had been confirmed using fluoroscopy and arthroscopy. Results Cartilaginous damage was noted in 21 patients, among whom 13 were treated by shaving and 8 underwent cartilaginous fragment removal. Fixation of the distal tibiofibular joint was conducted in 8 patients. From a postoperative radiographic evaluation, a good result in 100 cases and a fair outcome in 5 were confirmed. The clinical results were good in all, and no postoperative complications or pseudoarthrosis were noted. Conclusions The use of an arthroscope during treatment of malleolar fractures enables diagnosis and treatment of the lesions within the ankle joint, producing a satisfactory surgical outcome. Level of evidence Level IV, therapeutic study, case series (no control group).
TL;DR: The series of events elicited by AGE-2 and -3 may be responsible for some of the aspects of pathogenetic mechanisms in patients with diabetic neuropathy.
TL;DR: It is demonstrated that treadmill exercise stimulates bone formation and suppresses bone resorption, increases the serum 1,25-dihydroxyvitamin D3 level, and decreases the serum parathyroid hormone level, resulting in an increase in bone mass with stimulation of longitudinal bone growth, especially at weight-bearing sites, in young growing rats.
Abstract: The aim of the present study was to examine the effects of exercise on bone mass, bone metabolism, and calciotropic hormones in young growing rats. Twenty 6-week-old female Wistar rats were randomized into the following four groups with 5 animals each: 7 weeks of exercise, 7 weeks of sedentary control, 11 weeks of exercise, and 11 weeks of sedentary control. The exercise regimen consisted of running on a treadmill at 25 m/min for 1 h each day on 5 days a week. After each period of exercise, the bone mineral content (BMC) of the tibia and fifth lumbar spine was measured by dual-energy X-ray absorptiometry, using a Lunar DPX-L instrument. The femoral length and levels of bone markers and calciotropic hormones were also assessed. Seven and 11 weeks of exercise increased the serum osteocalcin and 1,25-dihydroxyvitamin D(3) levels, and decreased the serum parathyroid level. Seven weeks of exercise decreased the urinary deoxypyridinoline level, and 11 weeks of exercise increased the serum alkaline phosphatase level and decreased the serum tartrate-resistant acid phosphatase level. As a result, 7 and 11 weeks of exercise increased the femoral length and tibial BMC, but did not alter the lumbar BMC. The present study demonstrates that treadmill exercise stimulates bone formation and suppresses bone resorption, increases the serum 1,25-dihydroxyvitamin D(3) level, and decreases the serum parathyroid hormone level, resulting in an increase in bone mass with stimulation of longitudinal bone growth, especially at weight-bearing sites, in young growing rats. Further studies with long-term exercise may be needed to obtain a positive effect on the lumbar BMC.
TL;DR: A look over the series of peptides included in this family of stress peptides, especially in terms of the versatility of biological actions, along with the various characters of the receptors.
TL;DR: In this article, inheritance of the 1aminocyclopropane-1-carboxylic acid synthase (ACS) gene was determined for 50 apple cultivars/advanced selections and 101 F1 seedlings from five populations.
Abstract: The 1-aminocyclopropane-1-carboxylic acid synthase (ACS) gene is a member of the ACS gene family that is involved in apple (Malus × domestica Borkh.) fruit ripening. Presence of an allele (Md-ACS1-2) of this gene is associated with low internal ethylene concentration in some apple cultivars. In this study, inheritance of Md-ACS1 was determined for 50 apple cultivars/advanced selections and 101 F1 seedlings from five populations. Following this, the softening pattern of apples stored at 20°C for up to 40 days was examined using 35 fruiting cultivars/selections of defined Md-ACS1 status. Md-ACS1 is inherited in a Mendelian fashion and was found to be linked to fruit softening. Maturity season of genotypes also significantly affected fruit softening. Late-season genotypes in the Md-ACS1-2/2 class had the slowest rate of softening, while early-season Md-ACS1-1/1 genotypes had the most rapid softening rate. The implications of these results are discussed in relation to parental selection and breeding for storage ability in apple.