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Find video protocols related to scientific articles indexed in Pubmed.
Attempt of correlative observation of morphological synaptic connectivity by combining confocal laser-scanning microscope and FIB-SEM for immunohistochemical staining technique.
Microscopy (Oxf)
PUBLISHED: 11-01-2014
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Ten years have passed since a serial block-face scanning electron microscopy (SBF-SEM) method was developed [1]. In this innovative method, samples were automatically sectioned with an ultramicrotome placed inside a scanning electron microscope column, and the block surfaces were imaged one after another by SEM to capture back-scattered electrons. The contrast-inverted images obtained by the SBF-SEM were very similar to those acquired using conventional TEM. SFB-SEM has made easy to acquire image stacks of the transmission electron microscopy (TEM) in the mesoscale, which is taken with the confocal laser-scanning microcopy(CF-LSM).Furthermore, serial-section SEM has been combined with the focused ion beam (FIB) milling method [2]. FIB-incorporated SEM (FIB-SEM) has enabled the acquisition of three-dimensional images with a higher z-axis resolution com- pared to ultramicrotome-equipped SEM.We tried immunocytochemistry for FIB-SEM and correlated this immunoreactivity with that in CF-LSM. Dendrites of neurons in the rat neostriatum were visualized using a recombinant viral vector. Moreover, the thalamostriatal afferent terminals were immunolabeled with Cy5 fluorescence for vesicular glutamate transporter 2 (VGluT2). After detection of the sites of terminals apposed to the dendrites by using CF-LSM, GFP and VGluT2 immunoreactivities were further developed for EM by using immunogold/silver enhancement and immunoperoxidase/diaminobenzidine (DAB) methods, respectively.We showed that conventional immuno-cytochemical staining for TEM was applicable to FIB-SEM. Furthermore, several synaptic contacts, which were thought to exist on the basis of CF-LSM findings, were confirmed with FIB-SEM, revealing the usefulness of the combined method of CF-LSM and FIB-SEM.
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Measurement of eNO with portable analyzer might improve the management of persistent cough at primary care practice in Japan.
Clin Respir J
PUBLISHED: 09-29-2014
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There are some controversial reports that investigated the usefulness of exhaled nitric oxide (eNO) to predict the efficacy of inhaled corticosteroids (ICS) in chronic cough patients. Therefore, we retrospectively analyzed the usefulness of eNO measurement with portable analyzer to predict the requirement of ICS therapy in persistent cough (defined as lasting for 3 weeks or more) patients in Japan and investigated whether it might improve the management of persistent cough at primary care practice.
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Minimum Clinically Important Difference in Diffusing Capacity of the Lungs for Carbon Monoxide Among Patients with Severe and Very Severe Chronic Obstructive Pulmonary Disease.
COPD
PUBLISHED: 06-11-2014
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Abstract Background: The minimum clinically important difference (MCID) for diffusing capacity of the lungs for carbon monoxide (DLCO) has not yet been solidly established. Methods: We used the dataset of surgical cohort of National Emphysema Treatment Trial. Briefly, severe and very severe chronic obstructive pulmonary disease (COPD) patients who were candidate for volume reduction surgery and who could provide sufficient data at 12-month follow-up were included. We used two anchor methods using 6-minute walk distance (6MWD. MCID = 40 m) and forced expiratory volume in 1 sec (FEV1. MCID = 100 ml) as anchors, and two distribution methods. We proposed MCID with a median of estimated values. We estimated MCID for DLCO in raw value and % change from the baseline independently. Results: The surgical cohort included 356 patients, whose average age was 66.6 ± 5.5 years, and the average % predicted FEV1 was 27.8 ± 7.3%. The estimated MCID for DLCO in raw value and % change from the baseline were as follows: anchor method (average, 6MWD) 1.2 ml/min/mmHg, 17%; anchor method (average, FEV1) 0.7 ml/min/mmHg, 11%; anchor method (receiver operating characteristic, 6MWD) 1.1 ml/min/mmHg, 10%; anchor method (receiver operating characteristic, FEV1) 1.2 ml/min/mmHg, 3%; distribution method (0.3 units of standard deviation), 0.9 ml/min/mmHg, 11%; distribution method (standard error of measurement), 1.1 ml/min/mmHg. The median of these values was 1.1 ml/min/mmHg and 11%. Conclusion: We estimated the group-level MCID for DLCO for patients with severe and very severe COPD patients as 1.1 ml/min/mmHg and 11% of baseline DLCO.
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Intrapulmonary Schwannoma Diagnosed With Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration: Case Report.
Arch. Bronconeumol.
PUBLISHED: 06-08-2014
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A 47-year-old woman was referred to our hospital for further examination of a lung tumor. CT of the chest revealed a round, well-defined 2.4-cm nodule in S2, adjacent to right superior lobe bronchus. Endobronchial ultrasonography showed a well-defined, hypoechoic tumor with echogenic capsule and posterior acoustic enhancement. Diagnosis of schwannoma was confirmed from the specimen obtained by endobronchial ultrasound-guided transbronchial needle aspiration. She underwent tumorectomy due to the possibility of obstructive pneumonia. Pathology diagnosis from the surgical specimen was also schwannoma. Endobronchial ultrasound-guided transbronchial needle aspiration and findings with endobronchial ultrasonography might be helpful in the diagnosis of intrapulmonary schwannoma.
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Feasibility study of stereotactic body radiotherapy for peripheral lung tumors with a maximum dose of 100 Gy in five fractions and a heterogeneous dose distribution in the planning target volume.
J. Radiat. Res.
PUBLISHED: 05-15-2014
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We evaluated toxicity and outcomes for patients with peripheral lung tumors treated with stereotactic body radiation therapy (SBRT) in a dose-escalation and dose-convergence study. A total of 15 patients were enrolled. SBRT was performed with 60 Gy in 5 fractions (fr.) prescribed to the 60% isodose line of maximum dose, which was 100 Gy in 5 fr., covering the planning target volume (PTV) surface (60 Gy/5 fr. - (60%-isodose)) using dynamic conformal multiple arc therapy (DCMAT). The primary endpoint was radiation pneumonitis (RP) ? Grade 2 within 6 months. Toxicities were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Using dose-volumetric analysis, the trial regimen of 60 Gy/5 fr. - (60%-isodose) was compared with our institutional conventional regimen of 50 Gy/5 fr. - (80%-isodose). The enrolled consecutive patients had either a solitary peripheral tumor or two ipsilateral tumors. The median follow-up duration was 22.0 (12.0-27.0) months. After 6 months post-SBRT, the respective number of RP Grade 0, 1 and 2 cases was 5, 9 and 1. In the Grade 2 RP patient, the image showed an organizing pneumonia pattern at 6.0 months post-SBRT. No other toxicity was found. At last follow-up, there was no evidence of recurrence of the treated tumors. The target volumes of 60 Gy/ 5 fr. - (60%-isodose) were irradiated with a significantly higher dose than those of 50 Gy/5 fr. - (80%-isodose), while the former dosimetric parameters of normal lung were almost equivalent to the latter. SBRT with 60 Gy/5 fr. - (60%-isodose) using DCMAT allowed the delivery of very high and convergent doses to peripheral lung tumors with feasibility in the acute and subacute phases. Further follow-up is required to assess for late toxicity.
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Evidence suggesting that oral corticosteroids increase mortality in stable chronic obstructive pulmonary disease.
Respir. Res.
PUBLISHED: 03-25-2014
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Oral corticosteroids were used to control stable chronic obstructive pulmonary disease (COPD) decades ago. However, recent guidelines do not recommend long-term oral corticosteroids (LTOC) use for stable COPD patients, partly because it causes side-effects such as respiratory muscle deterioration and immunosuppression. Nonetheless, the impact of LTOC on life prognosis for stable COPD patients has not been clarified.
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Statins reduce all-cause mortality in chronic obstructive pulmonary disease: a systematic review and meta-analysis of observational studies.
Respir. Res.
PUBLISHED: 03-19-2014
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Recent observational studies have suggested that use of statins reduces mortality in patients suffering from chronic obstructive pulmonary disease. However, no meta-analysis has reported the pooled hazard ratio of statins to all-cause mortality.
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Dynorphin acts as a neuromodulator to inhibit itch in the dorsal horn of the spinal cord.
Neuron
PUBLISHED: 02-25-2014
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Menthol and other counterstimuli relieve itch, resulting in an antipruritic state that persists for minutes to hours. However, the neural basis for this effect is unclear, and the underlying neuromodulatory mechanisms are unknown. Previous studies revealed that Bhlhb5(-/-) mice, which lack a specific population of spinal inhibitory interneurons (B5-I neurons), develop pathological itch. Here we characterize B5-I neurons and show that they belong to a neurochemically distinct subset. We provide cause-and-effect evidence that B5-I neurons inhibit itch and show that dynorphin, which is released from B5-I neurons, is a key neuromodulator of pruritus. Finally, we show that B5-I neurons are innervated by menthol-, capsaicin-, and mustard oil-responsive sensory neurons and are required for the inhibition of itch by menthol. These findings provide a cellular basis for the inhibition of itch by chemical counterstimuli and suggest that kappa opioids may be a broadly effective therapy for pathological itch.
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Relationship between peri-operative outcomes and hospital surgical volume of total hip arthroplasty in Japan.
Health Policy
PUBLISHED: 02-10-2014
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This study aimed to evaluate the relationship between peri-operative complication of total hip arthroplasty (THA) and hospital surgical volume.
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Unbalanced excitability underlies offline reactivation of behaviorally activated neurons.
Nat. Neurosci.
PUBLISHED: 02-06-2014
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Hippocampal sharp waves (SWs)/ripples represent the reactivation of neurons involved in recently acquired memory and are crucial for memory consolidation. By labeling active cells with fluorescent protein under the control of an immediate-early gene promoter, we found that neurons that had been activated while mice explored a novel environment were preferentially reactivated during spontaneous SWs in hippocampal slices in vitro. During SWs, the reactivated neurons received strong excitatory synaptic inputs as opposed to a globally tuned network balance between excitation and inhibition.
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Psychological stress activates a dorsomedial hypothalamus-medullary raphe circuit driving brown adipose tissue thermogenesis and hyperthermia.
Cell Metab.
PUBLISHED: 01-10-2014
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Psychological stress-induced hyperthermia (PSH) is a fundamental autonomic stress response observed in many mammalian species. Here we show a hypothalamomedullary, glutamatergic neural pathway for psychological stress signaling that drives the sympathetic thermogenesis in brown adipose tissue (BAT) that contributes to PSH. Using in vivo drug nanoinjections into rat brain and thermotelemetry, we demonstrate that the rostral medullary raphe region (rMR) and dorsomedial hypothalamus (DMH) mediate a psychosocial stress-induced thermogenesis in BAT and PSH. Functional neuroanatomy indicates that the DMH functions as a hub for stress signaling, with monosynaptic projections to the rMR for sympathetic outputs and to the paraventricular hypothalamic nucleus for neuroendocrine outputs. Optogenetic experiments showed that the DMH-rMR monosynaptic pathway drives BAT thermogenesis and cardiovascular responses. These findings make an important contribution to our understanding of the central autonomic circuitries linking stress coping with energy homeostasis-potentially underlying the etiology of psychogenic fever, a major psychosomatic symptom.
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Chemotherapy with carboplatin and paclitaxel after failure of primary chemotherapy for advanced thymic carcinoma. A report of three cases and review of the literature.
Tumori
PUBLISHED: 12-12-2013
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For patients with inoperable thymic carcinoma, multidrug chemotherapy containing cisplatin and an anthracycline is often used as first-line chemotherapy. A commonly applied regimen is cisplatin + doxorubicin + vincristine + cyclophosphamide (ADOC). There are relatively few reports on the use of carboplatin and paclitaxel as first-line chemotherapy for thymic carcinoma. In addition, little is known about its efficacy as second-line chemotherapy in patients with advanced thymic carcinoma. We here report on three patients with thymic carcinoma who were treated with carboplatin and paclitaxel as second-line chemotherapy after failure of ADOC. According to the Response Evaluation Criteria in Solid Tumors version 1.1, one patient achieved a partial response and two patients achieved stable disease. The median progression-free survival was 6.7 months and the median overall survival exceeded 3 years. Toxicities were well tolerated. Chemotherapy with carboplatin and paclitaxel appears to be effective as second-line chemotherapy for some persons with thymic carcinoma who fail ADOC.
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Mycobacterium shinjukuense Lung Disease that was Successfully Treated with Antituberculous Drugs.
Intern. Med.
PUBLISHED: 12-03-2013
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An 80-year-old woman was referred to our hospital due to a persistent productive cough. Acid-fast staining and a commercial Mycobacterium tuberculosis identification kit with TRC (TRC kit) were positive. However, a false-positive result on the TRC kit was suspected because Mycobacterium tuberculosis was not detected in the sputum culture. Finally, Mycobacterium shinjukuense was detected in an analysis of the rpoB and hsp65 gene sequences. As the diagnostic criteria proposed by the American Thoracic Society were met, a diagnosis of Mycobacterium shinjukuense lung disease was made. Following treatment with isoniazid, rifampicin and ethambutol with drug susceptibility, the patients acid-fast culture became negative, and the areas of opacity improved.
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Decreased activities of daily living is a strong risk factor for liver injury by anti-tuberculosis drugs.
Respirology
PUBLISHED: 09-26-2013
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We evaluated the association between activities of daily living and drug-induced liver injury by anti-tuberculosis drugs.
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Ventral Medial Nucleus Neurons Send Thalamocortical Afferents More Widely and More Preferentially to Layer 1 than Neurons of the Ventral Anterior-Ventral Lateral Nuclear Complex in the Rat.
Cereb. Cortex
PUBLISHED: 08-24-2013
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Not only inhibitory afferent-dominant zone (IZ) of the ventral anterior-ventral lateral thalamic complex (VA-VL) but also the ventral medial nucleus (VM) is known to receive strong inputs from the basal ganglia and send axons to motor areas. We previously reported differences in axonal arborization between IZ neurons and the other VA-VL neurons in rats by single-neuron tracing with viral vectors. In the present study, the axonal arborization of single VM neurons was visualized by the same method, and compared with that of IZ neurons. VM neurons formed fewer axon collaterals in the striatum, but sent axon fibers more widely and more preferentially (79% of fibers) to layer 1 of cortical areas than IZ neurons. Furthermore, the VM seemed to contain at least 2 types of neurons; a major population of VM neurons sent axon fibers principally to motor-associated areas as VA-VL neurons did, and the other population projected mainly to orbital or cingulate areas. Although both VM and IZ neurons receive strong basal ganglia inputs, these results suggest that VM neurons, at a single neuron level, innervate the apical dendrites of cortical pyramidal neurons more intensely and more widely than IZ neurons.
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A Triruthenium Complex Capped by a Triply Bridging Oxoboryl Ligand.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 07-26-2013
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Building new bridges: A triply bridging oxoboryl ligand was formed by treatment of the ?3 -borylene complex [{Cp*Ru(?-H)}3 (?3 -PhCCH)(?3 -BH)] (Cp*=?(5) -C5 Me5 ) with H2 O. The multiple-bond character of the B?O bond was revealed by X-ray diffraction, spectroscopy, and a DFT calculation. Protonation of the ?3 -BO complex to give a cationic ?3 -hydroxyborylene complex clearly showed the highly polarized nature of the B(+) ?O(-) bond.
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Small, Moderate, and Large Changes, and the Minimum Clinically Important Difference in the University of California, San Diego Shortness of Breath Questionnaire.
COPD
PUBLISHED: 07-25-2013
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Abstract Minimum clinically important change of 5 points in the University of California, San Diego Shortness of Breath Questionnaire (SOBQ) is established, but cutoff values between a small, a moderate, and a large change are still unknown. We used the data set of National Emphysema Treatment Trial consisting of severe and very severe chronic obstructive pulmonary disease patients, whose mean age was 64 years. Changes from baseline to post-surgical 6-month follow-up were evaluated. The St. Georges Respiratory Questionnaire was used as anchor: |?SGRQ| < 4, meaningless change; 4 ? |?SGRQ| < 8, small change; 8 ? |?SGRQ| < 13, moderate change; 13 ? |?SGRQ|, large change. We decided the final cutoff values for the SOBQ as medians of the three anchor methods. We also decided the range of cutoff values as the range of three values. In a cohort of surgically treated patients (N = 484), we propose value of 5 (range 5-6), 11 (range 9-15), and 16 (range 14-20) for the cutoff values between a meaningless and a small change (minimum clinically important difference), a small and a moderate change, and a moderate and a large change, respectively. In a cohort of medically treated patients, numbers of patients categorized according to ?SOBQ scores were similar to those of the patients categorizes according to the ?SGRQ (N = 480) or ?Forced expiratory volume in 1 second (N = 425). We propose group-level cutoff values and range between a small, a moderate, and a large changes.
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Poor performance status is a strong predictor for death in patients with smear-positive pulmonary TB admitted to two Japanese hospitals.
Trans. R. Soc. Trop. Med. Hyg.
PUBLISHED: 06-13-2013
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Estimation of performance status (PS) has been assessed as a tool to determine which patients with newly diagnosed pulmonary TB (PTB) are most at risk of dying. This simple prediction rule has not been validated in patients with PTB with different background characteristics and from different geographic areas.
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Quantitative analysis of axon bouton distribution of subthalamic nucleus neurons in the rat by single neuron visualization with a viral vector.
J. Comp. Neurol.
PUBLISHED: 04-19-2013
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The subthalamic nucleus (STN) of the basal ganglia plays a key role in motor control, and STN efferents are known to mainly target the external segment of the globus pallidus (GPe), entopeduncular nucleus (Ep), and substantia nigra (SN) with some axon collaterals to the other regions. However, it remains to be clarified how each STN neuron projects axon fibers and collaterals to those target nuclei of the STN. Here we visualized the whole axonal arborization of single STN neurons in the rat brain by using a viral vector expressing membrane-targeted green fluorescent protein, and examined the distribution of axon boutons in those target nuclei. The vast majority (8-9) of 10 reconstructed STN neurons projected to the GPe, SN, caudate-putamen (CPu), and Ep, which received, on average ± SD, 457 ± 425, 400 ± 347, 126 ± 143, and 106 ± 100 axon boutons per STN neuron, respectively. Furthermore, the density of axon boutons in the GPe was highest among these nuclei. Although these target nuclei were divided into calbindin-rich and -poor portions, STN projection showed no exclusive preference for those portions. Since STN neurons mainly projected not only to the GPe, SN, and Ep but also to the CPu, the subthalamostriatal projection might serve as a positive feedback path for the striato-GPe-subthalamic disinhibitory pathway, or work as another route of cortical inputs to the striatum through the corticosubthalamostriatal disynaptic excitatory pathway.
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EphA4-dependent axon retraction and midline localization of Ephrin-B3 are disrupted in the spinal cord of mice lacking mDia1 and mDia3 in combination.
Genes Cells
PUBLISHED: 04-11-2013
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mDia is an actin nucleator and polymerization factor regulated by the small GTPase Rho and consists of three isoforms. Here, we found that mice lacking mDia1 and mDia3, two isoforms expressed in the brain, in combination (mDia-DKO mice) show impaired left-right limb coordination during locomotion and aberrant midline crossing of axons of corticospinal neurons and spinal cord interneurons. Given that mice lacking Ephrin-B3-EphA4 signaling show a similar impairment in locomotion, we examined whether mDia is involved in Ephrin-B3-EphA4 signaling for axon repulsion. In primary cultured neurons, mDia deficiency impairs growth cone collapse and axon retraction induced by chemo-repellants including EphA ligands. In mDia-DKO mice, the Ephrin-B3-expressing midline structure in the spinal cord is disrupted, and axons aberrantly cross the spinal cord midline preferentially through the region devoid of Ephrin-B3. Therefore, mDia plays multiple roles in the proper formation of the neural network in vivo.
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Salvage stereotactic ablative irradiation for isolated postsurgical local recurrence of lung cancer.
Ann. Thorac. Surg.
PUBLISHED: 04-09-2013
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For isolated postsurgical local recurrences (IPSLR) of lung cancer, salvage resection is often unfeasible due to a high risk of morbidity and death. Stereotactic ablative body radiotherapy (SABR) provides excellent therapeutic effects, with mild toxicities, for patients with medically inoperable lung cancer. However, the outcomes of SABR for IPSLR have not been reported.
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Sensitivity and specificity of the Streptococcus pneumoniae urinary antigen test for unconcentrated urine from adult patients with pneumonia: a meta-analysis.
Respirology
PUBLISHED: 03-28-2013
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Studies on the sensitivity and specificity of the Binax Now Streptococcus pneumonia urinary antigen test (index test) show considerable variance of results. Those written in English provided sufficient original data to evaluate the sensitivity and specificity of the index test using unconcentrated urine to identify S. pneumoniae infection in adults with pneumonia. Reference tests were conducted with at least one culture and/or smear. We estimated sensitivity and two specificities. One was the specificity evaluated using only patients with pneumonia of identified other aetiologies (specificity (other)). The other was the specificity evaluated based on both patients with pneumonia of unknown aetiology and those with pneumonia of other aetiologies (specificity (unknown and other)) using a fixed model for meta-analysis. We found 10 articles involving 2315 patients. The analysis of 10 studies involving 399 patients yielded a pooled sensitivity of 0.75 (95% confidence interval: 0.71-0.79) without heterogeneity or publication bias. The analysis of six studies involving 258 patients yielded a pooled specificity (other) of 0.95 (95% confidence interval: 0.92-0.98) without no heterogeneity or publication bias. We attempted to conduct a meta-analysis with the 10 studies involving 1916 patients to estimate specificity (unknown and other), but it remained unclear due to moderate heterogeneity and possible publication bias. In our meta-analysis, sensitivity of the index test was moderate and specificity (other) was high; however, the specificity (unknown and other) remained unclear.
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Mammal retinal distribution of ENKergic amacrine cells and their neurochemical features: evidence from the PPE-GFP transgenic mice.
Neurosci. Lett.
PUBLISHED: 02-28-2013
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The neuroactive peptide enkephalin (ENK) has been postulated to play important roles in modulating visual information. The retinal presence of ENKergic cells has been revealed with conventional morphological protocols targeting ENK molecule especially in avian, however, the detailed distribution of ENKergic cells and their specific neurochemical features in the mammal retina remain unclear because of the difficulties in visualizing ENKergic cells efficiently and reliably. To address this question, we took advantage of the preproenkephalin-green fluorescent protein (PPE-GFP) transgenic mice previously generated and identified in our group, and identified the neurochemical characteristics of retinal ENKergic cells. The majority of ENKergic cells occupied the proximal inner nuclear layer with a few displaced in the ganglion cell layer. Further double labeling revealed that most of these ENKergic amacrine cells used inhibitory glycine or gamma-aminobutyric acid as the primary neurotransmitter. However, some of them also utilized excitatory glutamate as the primary neurotransmitter. The present findings suggest that the retinal ENKergic cells fall into a subpopulation of amacrine cells and show predominantly inhibitory as well as less dominantly excitatory neurochemical features. Our findings offered comprehensive morphological evidence for the function of ENKergic amacrine cells of mammal species.
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Preoperative chemotherapy is effective for stage III resectable non--small-cell lung cancer: metaanalysis of 16 trials.
Clin Lung Cancer
PUBLISHED: 02-20-2013
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The benefit of preoperative chemotherapy for resectable non-small-cell lung cancer is still controversial.
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Correlative analysis of immunoreactivity in confocal laser-scanning microscopy and scanning electron microscopy with focused ion beam milling.
Front Neural Circuits
PUBLISHED: 02-05-2013
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Recently, three-dimensional reconstruction of ultrastructure of the brain has been realized with minimal effort by using scanning electron microscopy (SEM) combined with focused ion beam (FIB) milling (FIB-SEM). Application of immunohistochemical staining in electron microscopy (EM) provides a great advantage in that molecules of interest are specifically localized in ultrastructures. Thus, we applied immunocytochemistry for FIB-SEM and correlated this immunoreactivity with that in confocal laser-scanning microcopy (CF-LSM). Dendrites of medium-sized spiny neurons in the rat neostriatum were visualized using a recombinant viral vector, which labeled the infected neurons with membrane-targeted GFP in a Golgi stain-like fashion. Moreover, the thalamostriatal afferent terminals were immunolabeled with Cy5 fluorescence for vesicular glutamate transporter 2 (VGluT2). After detection of the sites of terminals apposed to the dendrites by using CF-LSM, GFP and VGluT2 immunoreactivities were further developed for EM by using immunogold/silver enhancement and immunoperoxidase/diaminobenzidine (DAB) methods, respectively. In contrast-inverted FIB-SEM images, silver precipitations and DAB deposits were observed as fine dark grains and diffuse dense profiles, respectively, indicating that these immunoreactivities were as easily recognizable as those in the transmission electron microscopy (TEM) images. Furthermore, in the sites of interest, some appositions displayed synaptic specializations of an asymmetric type. Thus, the present method was useful in the three-dimensional analysis of immunocytochemically differentiated synaptic connections in the central neural circuit.
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Differential expression of VGLUT1 or VGLUT2 in the trigeminothalamic or trigeminocerebellar projection neurons in the rat.
Brain Struct Funct
PUBLISHED: 02-05-2013
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The vesicular glutamate transporters, VGLUT1 and VGLUT2, reportedly display complementary distribution in the rat brain. However, co-expression of them in single neurons has been reported in some brain areas. We previously found co-expression of VGLUT1 and VGLUT2 mRNAs in a number of single neurons in the principal sensory trigeminal nucleus (Vp) of the adult rat; the majority of these neurons sent their axons to the thalamic regions around the posteromedial ventral nucleus (VPM) and the posterior nuclei (Po). It is well known that trigeminothalamic (T-T) projection fibers arise not only from the Vp but also from the spinal trigeminal nucleus (Vsp), and that trigeminocerebellar (T-C) projection fibers take their origins from both of the Vp and Vsp. Thus, in the present study, we examined the expression of VGLUT1 and VGLUT2 in Vp and Vsp neurons that sent their axons to the VPM/Po regions or the cortical regions of the cerebellum. For this purpose, we combined fluorescence in situ hybridization (FISH) histochemistry with retrograde tract-tracing; immunofluorescence histochemistry was also combined with anterograde tract-tracing. The results indicate that glutamatergic Vsp neurons sending their axons to the cerebellar cortical regions mainly express VGLUT1, whereas glutamatergic Vsp neurons sending their axons to the thalamic regions express VGLUT2. The present data, in combination with those of our previous study, indicate that glutamatergic Vp neurons projecting to the cerebellar cortical regions express mainly VGLUT1, whereas the majority of glutamatergic Vp neurons projecting to the thalamus co-express VGLUT1 and VGLUT2.
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Dynamic live imaging of bone: opening a new era with bone histodynametry.
J. Bone Miner. Metab.
PUBLISHED: 02-01-2013
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Recent advances in optical imaging with two-photon excitation microscopy have enabled visualization of the inside of intact bone tissues in living animals. Using these advanced techniques, the dynamic behaviors of live bone cells and static histological information on bone tissue structures can be elucidated. The migration and positioning of osteoclast precursor monocytes, the bone-resorbing function of mature osteoclasts, and its functional coupling with bone-replenishing osteoblasts have been evaluated, including their dynamic properties in intact live bones. This novel bone histodynametric methodology, combined with conventional histomorphometric analyses, will surely contribute to opening of a new era in bone and mineral research.
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Long-acting beta-agonists reduce mortality of patients with severe and very severe chronic obstructive pulmonary disease: a propensity score matching study.
Respir. Res.
PUBLISHED: 01-31-2013
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Long-acting beta-agonists were one of the first-choice bronchodilator agents for stable chronic obstructive pulmonary disease. But the impact of long-acting beta-agonists on mortality was not well investigated.
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Modeling Alzheimers disease with iPSCs reveals stress phenotypes associated with intracellular A? and differential drug responsiveness.
Cell Stem Cell
PUBLISHED: 01-18-2013
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Oligomeric forms of amyloid-? peptide (A?) are thought to play a pivotal role in the pathogenesis of Alzheimers disease (AD), but the mechanism involved is still unclear. Here, we generated induced pluripotent stem cells (iPSCs) from familial and sporadic AD patients and differentiated them into neural cells. A? oligomers accumulated in iPSC-derived neurons and astrocytes in cells from patients with a familial amyloid precursor protein (APP)-E693? mutation and sporadic AD, leading to endoplasmic reticulum (ER) and oxidative stress. The accumulated A? oligomers were not proteolytically resistant, and docosahexaenoic acid (DHA) treatment alleviated the stress responses in the AD neural cells. Differential manifestation of ER stress and DHA responsiveness may help explain variable clinical results obtained with the use of DHA treatment and suggests that DHA may in fact be effective for a subset of patients. It also illustrates how patient-specific iPSCs can be useful for analyzing AD pathogenesis and evaluating drugs.
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Cell type-specific inhibitory inputs to dendritic and somatic compartments of parvalbumin-expressing neocortical interneuron.
J. Neurosci.
PUBLISHED: 01-11-2013
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Parvalbumin (PV)-producing fast-spiking neurons are well known to generate gamma oscillation by mutual chemical and electrical connections in the neocortex. Although it was clearly demonstrated that PV neurons form a dense gap junction network with each other not only at the proximal sites but also at the distal dendrites, comprehensive quantitative data on the chemical connections are still lacking. To elucidate the connectivity, we investigated inhibitory inputs to PV neurons in the somatosensory cortex, using the transgenic mice in which the dendrites and cell bodies of PV neurons were clearly visualized. We first examined GABAergic inputs to PV neurons by labeling postsynaptic and presynaptic sites with the immunoreactivities for gephyrin and vesicular GABA transporter. The density of GABAergic inputs was highest on the cell bodies, and almost linearly decreased to the distal dendrites. We then investigated inhibitory inputs from three distinct subgroups of GABAergic interneurons by visualizing the axon terminals immunopositive for PV, somatostatin (SOM), or vasoactive intestinal polypeptide (VIP). PV and SOM inputs were frequently located on the dendrites with the ratio of 2.5:1, but much less on the cell bodies. By contrast, VIP inputs clearly preferred the cell bodies to the dendrites. Consequently, the dendritic and somatic compartments of PV neurons received ?60 and 62% of inhibitory inputs from PV and VIP neurons, respectively. This compartmental organization of inhibitory inputs suggests that PV neurons, together with gap junctions, constitute mutual connections at the dendrites, and that their activities are negatively controlled by the somatic inputs of VIP neurons.
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Stereotactic ablative body radiation therapy for octogenarians with non-small cell lung cancer.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 01-02-2013
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To retrospectively investigate treatment outcomes of stereotactic ablative body radiation therapy (SABR) for octogenarians with non-small cell lung cancer (NSCLC).
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SNP (-617C>A) in ARE-like loci of the NRF2 gene: a new biomarker for prognosis of lung adenocarcinoma in Japanese non-smoking women.
PLoS ONE
PUBLISHED: 01-01-2013
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The transcription factor NRF2 plays a pivotal role in protecting normal cells from external toxic challenges and oxidative stress, whereas it can also endow cancer cells resistance to anticancer drugs. At present little information is available about the genetic polymorphisms of the NRF2 gene and their clinical relevance. We aimed to investigate the single nucleotide polymorphisms in the NRF2 gene as a prognostic biomarker in lung cancer.
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Local connections of excitatory neurons in motor-associated cortical areas of the rat.
Front Neural Circuits
PUBLISHED: 01-01-2013
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In spite of recent progress in brain sciences, the local circuit of the cerebral neocortex, including motor areas, still remains elusive. Morphological works on excitatory cortical circuitry from thalamocortical (TC) afferents to corticospinal neurons (CSNs) in motor-associated areas are reviewed here. First, TC axons of motor thalamic nuclei have been re-examined by the single-neuron labeling method. There are middle layer (ML)-targeting and layer (L) 1-preferring TC axon types in motor-associated areas, being analogous to core and matrix types, respectively, of Jones (1998) in sensory areas. However, the arborization of core-like motor TC axons spreads widely and disregards the columnar structure that is the basis of information processing in sensory areas, suggesting that motor areas adopt a different information-processing framework such as area-wide laminar organization. Second, L5 CSNs receive local excitatory inputs not only from L2/3 pyramidal neurons but also from ML spiny neurons, the latter directly processing cerebellar information of core-like TC neurons (TCNs). In contrast, basal ganglia information is targeted to apical dendrites of L2/3 and L5 pyramidal neurons through matrix TCNs. Third, L6 corticothalamic neurons (CTNs) are most densely innervated by ML spiny neurons located just above CTNs. Since CTNs receive only weak connections from L2/3 and L5 pyramidal neurons, the TC recurrent circuit composed of TCNs, ML spiny neurons and CTNs appears relatively independent of the results of processing in L2/3 and L5. It is proposed that two circuits sharing the same TC projection and ML neurons are embedded in the neocortex: one includes L2/3 and L5 neurons, processes afferent information in a feedforward way and sends the processed information to other cortical areas and subcortical regions; and the other circuit participates in a dynamical system of the TC recurrent circuit and may serve as the basis of autonomous activity of the neocortex.
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[A case of IgG4-related disease with deterioration in pulmonary and pituitary involvements during a 10-year clinical course of inflammatory pseudotumor].
Nihon Kokyuki Gakkai Zasshi
PUBLISHED: 12-23-2011
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A 71-year-old man underwent pleural biopsy due to left pleural effusion and pleural thickening in August, 2001. An inflammatory pseudotumor (IPT) was diagnosed, and therefore systemic oral steroid therapy (prednisolone [PSL] 30 mg/day) was initiated. However, after tapering PSL to 7.5 mg/day, a complication of secondary central diabetes insipidus due to hypophysitis developed in 2008. As his pulmonary condition deteriorated over time and he began to experience exertional dyspnea, he was admitted to our hospital for re-evaluation of the disease in October, 2010. High-resolution CT (HRCT) revealed pulmonary involvements distributed in the interstitium and a high serum IgG4 level (240 mg/dl). Upon re-evaluating the pleural biopsy specimens of the first visit, we found lymphoplasmacytic-type IPT with approximately 10% IgG4-positive plasma cells in the affected areas. After increasing the PSL dose up to 0.6 mg/kg/day, his serum IgG4 levels decreased, his dyspnea improved, and the radiological findings of his pulmonary and pituitary involvements improved. This case was diagnosed as lymphoplasmacytic type IPT which appeared to be highly homologous with IgG4-related disease due to high serum levels of IgG4, pituitary involvements and the observed efficacy of PSL.
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A morphological analysis of thalamocortical axon fibers of rat posterior thalamic nuclei: a single neuron tracing study with viral vectors.
Cereb. Cortex
PUBLISHED: 12-20-2011
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The rostral sector of the posterior thalamic nuclei (POm) is, together with the ventral posterior nuclei (VP), involved in somatosensory information processing in rodents. The POm receives inputs from the spinal cord and trigeminal nuclei and projects to the primary somatosensory (S1) cortex and other cortical areas. Although thalamocortical axons of single VP neurons are well known to innervate layer (L) 4 of the S1 cortex with distinct columnar organization, those of POm neurons have not been elucidated yet. In the present study, we investigated complete axonal and dendritic arborizations of single POm neurons in rats by visualizing the processes with Sindbis viruses expressing membrane-targeted fluorescent protein. When we divided the POm into anterior and posterior parts according to calbindin immunoreactivity, dendrites of posterior POm neurons were wider but less numerous than those of anterior neurons. More interestingly, axon fibers of anterior POm neurons were preferentially distributed in L5 of the S1 cortex, whereas those of posterior neurons were principally spread in L1 with wider and sparser arborization than those of anterior neurons. These results suggest that the POm is functionally segregated into anterior and posterior parts and that the 2 parts may play different roles in somatosensory information processing.
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Local connections of excitatory neurons to corticothalamic neurons in the rat barrel cortex.
J. Neurosci.
PUBLISHED: 12-16-2011
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Corticothalamic projection neurons in the cerebral cortex constitute an important component of the thalamocortical reciprocal circuit, an essential input/output organization for cortical information processing. However, the spatial organization of local excitatory connections to corticothalamic neurons is only partially understood. In the present study, we first developed an adenovirus vector expressing somatodendritic membrane-targeted green fluorescent protein. After injection of the adenovirus vector into the ventrobasal thalamic complex, a band of layer (L) 6 corticothalamic neurons in the rat barrel cortex were retrogradely labeled. In addition to their cell bodies, fine dendritic spines of corticothalamic neurons were well visualized without the labeling of their axon collaterals or thalamocortical axons. In cortical slices containing retrogradely labeled L6 corticothalamic neurons, we intracellularly stained single pyramidal/spiny neurons of L2-6. We examined the spatial distribution of contact sites between the local axon collaterals of each pyramidal neuron and the dendrites of corticothalamic neurons. We found that corticothalamic neurons received strong and focused connections from L4 neurons just above them, and that the most numerous nearby and distant sources of local excitatory connections to corticothalamic neurons were corticothalamic neurons themselves and L6 putative corticocortical neurons, respectively. These results suggest that L4 neurons may serve as an important source of local excitatory inputs in shaping the cortical modulation of thalamic activity.
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[Two cases of juvenile-onset and adult-onset recurrent respiratory papillomatosis].
Nihon Kokyuki Gakkai Zasshi
PUBLISHED: 11-12-2011
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We recently experienced one each of 2 types of recurrent respiratory papillomatosis (RRP). Case 1 (juvenile-onset type): A 30-year-old woman presenting with bloody sputum and large tumors with cavities on her chest Xray film, was referred to our hospital. She had been diagnosed with laryngeal papillomatosis when she was three years old. According to our bronchoscopical examination biopsy, she was diagnosed with squamous cell carcinoma of the lung in addition to papillomatosis of the trachea and bronchus. Although chemotherapy was performed, she died 2 years after the diagnosis of lung cancer without any distinct treatment efficacy. Case 2 (adult-onset type): A 43 year-old woman presenting with fever and dry cough visited our hospital. Chest CT revealed that there was narrowing of bilateral main bronchi and hilar lymphadenopathy. Bronchoscopic examination revealed diffuse papilloma distributed extensively from the trachea to bilateral main bronchi. However, she recovered spontaneously in 6 months and has remained stable without recurrence. Both cases were diagnosed with RRP based on the separation of HPV in case 1 and pathological findings of koilocytosis in case 2. Case 1 was complicated with squamous cell carcinoma of the lung in the clinical course, presumably due to occurrence of malignant conversion of papillomatosis. Since RRP is a rare but refractory disease, novel effective treatment is necessary.
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Local connections of layer 5 GABAergic interneurons to corticospinal neurons.
Front Neural Circuits
PUBLISHED: 07-30-2011
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In the local circuit of the cerebral cortex, GABAergic inhibitory interneurons are considered to work in collaboration with excitatory neurons. Although many interneuron subgroups have been described in the cortex, local inhibitory connections of each interneuron subgroup are only partially understood with respect to the functional neuron groups that receive these inhibitory connections. In the present study, we morphologically examined local inhibitory inputs to corticospinal neurons (CSNs) in motor areas using transgenic rats in which GABAergic neurons expressed fluorescent protein Venus. By analysis of biocytin-filled axons obtained with whole-cell recording/staining in cortical slices, we classified fast-spiking (FS) neurons in layer (L) 5 into two types, FS1 and FS2, by their high and low densities of axonal arborization, respectively. We then investigated the connections of FS1, FS2, somatostatin (SOM)-immunopositive, and other (non-FS/non-SOM) interneurons to CSNs that were retrogradely labeled in motor areas. When close appositions between the axon boutons of the intracellularly labeled interneurons and the somata/dendrites of the retrogradely labeled CSNs were examined electron-microscopically, 74% of these appositions made symmetric synaptic contacts. The axon boutons of single FS1 neurons were two- to fourfold more frequent in appositions to the somata/dendrites of CSNs than those of FS2, SOM, and non-FS/non-SOM neurons. Axosomatic appositions were most frequently formed with axon boutons of FS1 and FS2 neurons (approximately 30%) and least frequently formed with those of SOM neurons (7%). In contrast, SOM neurons most extensively sent axon boutons to the apical dendrites of CSNs. These results might suggest that motor outputs are controlled differentially by the subgroups of L5 GABAergic interneurons in cortical motor areas.
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Dynorphin is expressed primarily by GABAergic neurons that contain galanin in the rat dorsal horn.
Mol Pain
PUBLISHED: 07-26-2011
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The opioid peptide dynorphin is expressed by certain neurons in the superficial dorsal horn of the spinal cord, but little is known about the types of cell that contain dynorphin. In this study, we have used an antibody against the dynorphin precursor preprodynorphin (PPD), to reveal the cell bodies and axons of dynorphin-expressing neurons in the rat spinal cord. The main aims were to estimate the proportion of neurons in each of laminae I-III that express dynorphin and to determine whether they are excitatory or inhibitory neurons.
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Spatial and temporal distribution patterns of enkephalinergic neurons in adult and developing retinas of the preproenkephalin-green fluorescent protein transgenic mouse.
Cells Tissues Organs (Print)
PUBLISHED: 05-26-2011
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Enkephalin (ENK) peptides are present in the retina of several vertebrate species and play a crucial role in establishing specific circuits during retinal development. However, there is no information available concerning the development of ENKergic neurons in the mouse retina. To address this question, we used preproenkephalin-enhanced green fluorescent protein (GFP) transgenic mice, in which ENKergic neurons are revealed by GFP. Our results showed that most GFP-positive cells were located in the proximal part of the inner nuclear layer with a scattering of GFP-immunoreactive cells in the ganglion cell layer (GCL) in the adult retina. Double immunostaining with syntaxin indicates that GFP expression was restricted to a population of amacrine cells. The proportions of glycine transporter-1 and ?-aminobutyric acid-positive cells among ENKergic neurons were 57.3 ± 2.4% and 10.1 ± 1.8%, respectively. We then injected retrograde tracer into the superior colliculus and observed that none of the ENKergic neurons in the GCL were retrogradely labeled with the tracer. GFP-positive cells were first observed at embryonic day (E) 15 in the inner neuroblastic layer at only very low levels, which gradually increased until E18. After birth, there was a steep rise in GFP expression levels, reaching maximal activity by postnatal day (P) 7. The distribution and intensity of GFP-positive cells at P15 were similar to those of adult retina. It was found that immunoreactive processes in the inner plexiform layer formed strongly stained patches. The present results provide detailed morphological evidence of the cell type and spatial and temporal distribution of ENKergic neurons in the retina.
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Anti-A? drug screening platform using human iPS cell-derived neurons for the treatment of Alzheimers disease.
PLoS ONE
PUBLISHED: 05-26-2011
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Alzheimers disease (AD) is a neurodegenerative disorder that causes progressive memory and cognitive decline during middle to late adult life. The AD brain is characterized by deposition of amyloid ? peptide (A?), which is produced from amyloid precursor protein by ?- and ?-secretase (presenilin complex)-mediated sequential cleavage. Induced pluripotent stem (iPS) cells potentially provide an opportunity to generate a human cell-based model of AD that would be crucial for drug discovery as well as for investigating mechanisms of the disease.
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Tangential migration and proliferation of intermediate progenitors of GABAergic neurons in the mouse telencephalon.
Development
PUBLISHED: 05-11-2011
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In the embryonic neocortex, neuronal precursors are generated in the ventricular zone (VZ) and accumulate in the cortical plate. Recently, the subventricular zone (SVZ) of the embryonic neocortex was recognized as an additional neurogenic site for both principal excitatory neurons and GABAergic inhibitory neurons. To gain insight into the neurogenesis of GABAergic neurons in the SVZ, we investigated the characteristics of intermediate progenitors of GABAergic neurons (IPGNs) in mouse neocortex by immunohistochemistry, immunocytochemistry, single-cell RT-PCR and single-cell array analysis. IPGNs were identified by their expression of some neuronal and cell cycle markers. Moreover, we investigated the origins of the neocortical IPGNs by Cre-loxP fate mapping in transgenic mice and the transduction of part of the telencephalic VZ by Cre-reporter plasmids, and found them in the medial and lateral ganglionic eminence. Therefore, they must migrate tangentially within the telencephalon to reach the neocortex. Cell-lineage analysis by simple-retrovirus transduction revealed that the neocortical IPGNs self-renew and give rise to a small number of neocortical GABAergic neurons and to a large number of granule and periglomerular cells in the olfactory bulb. IPGNs are maintained in the neocortex and may act as progenitors for adult neurogenesis.
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[Evaluation of 320-row area detector computed tomography (ADCT) coronary angiography for patients with atrial fibrillation].
Nihon Hoshasen Gijutsu Gakkai Zasshi
PUBLISHED: 05-03-2011
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The aim of this study was to evaluate 320-row area detector CT (ADCT) for patients with atrial fibrillation (Af) based on simulated exposure using electrocardiogram RR intervals and comparison with the findings of coronary CT angiography (CCTA) using 64-row multi slice CT (MSCT). The probability of including RR intervals of 900 ms or more was calculated when the acquisition time was varied from 1 to 4 beats. Overall, 51 patients with Af who underwent CCTA were examined. The exposure time for CCTA, the total dose length product (DLP) for the examination, and the image quality (scored 0 to 3: poor to excellent) were compared between ADCT and MSCT. The probability of including RR intervals of 900 ms or more was highly significantly increased at 3 beats of acquisition time. The exposure time using ADCT was reduced by 75% compared with MSCT (ADCT/MSCT: 2.8/11.3 s), and the total DLP was reduced by 40% (ADCT/MSCT: 1398/2277 mGy·cm). Moreover, ADCT provided diagnosable images in all cases, and the mean image quality score for ADCT was significantly higher than that for MSCT (ADCT/MSCT: 2.8/2.4). Thus, 320-row ADCT at 3 beats of acquisition time can provide CCTA images of acceptable quality for patients with Af.
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Clinical significance of computed tomographic assessment and anatomic features of the inferior alveolar canal as risk factors for injury of the inferior alveolar nerve at third molar surgery.
J. Oral Maxillofac. Surg.
PUBLISHED: 04-29-2011
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To assess the clinical features of the inferior alveolar canal (IAC) using computed tomography (CT) and to analyze the significance of CT examination at third molar surgery.
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Anisotropic distribution of thalamocortical boutons in barrels.
J. Neurosci.
PUBLISHED: 04-29-2011
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A characteristic feature of the somatosensory cortex in rodents is the presence of discrete cellular aggregates in layer 4 (barrels) that process input from the mystacial vibrissae. Just like thalamic cells that relay vibrissal information to the barrels, barrel cells display directional preference to whisker motion. The present study examined whether the projection of single thalamic cells into a barrel is consistent with the existence of an orderly map of direction preference. The direction preference of single thalamic cells was assessed, and axonal projections were visualized after juxtacellular labeling with biotinylated dextran. Results show that the terminal field of individual thalamic neurons in a barrel is markedly anisotropic and that the location of boutons with respect to the somatotopic map is either positively or negatively correlated with the angular tuning of the thalamic neuron. These results indicate that angular tuning is not represented across a systematic map with fixed anteroposterior/mediolateral coordinates in a barrel. The actual significance of the direction-dependent segregation of thalamocortical terminals in barrels may only come to light in the context of active sensing.
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Clinical efficacy of carbapenems on hospital-acquired pneumonia in accordance with the Japanese Respiratory Society Guidelines for management of HAP.
J. Infect. Chemother.
PUBLISHED: 04-07-2011
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Hospital-acquired pneumonia (HAP) is the second most common cause of hospital-acquired infection and is the leading cause of death. In 2002, the Japanese Respiratory Society (JRS) published guidelines for the diagnosis and treatment of HAP (JRS GL 2002). In these guidelines, treatment with carbapenems is recommended for all disease types of HAP, excluding cases of mild or moderate pneumonia with no risk factors, and cases with early-onset ventilation-acquired pneumonia. To evaluate the efficacy of carbapenems on HAP in accordance with JRS GL 2002, we conducted a prospective study of HAP patients treated with carbapenems based on JRS GL 2002. The results of this study were also analyzed based on the revised guidelines published in June 2008 (JRS GL 2008), and the validity of the new guidelines was examined. Of the 33 subjects, 19 were judged as responders to the treatment, corresponding to a response rate of 57.6%. There were 3 deaths, corresponding to a mortality rate of 9.1%. The efficacy of carbapenems for the treatment of HAP based on JRS GL 2002 was confirmed. The severity rating system in JRS GL 2002 has a tendency to overestimate the severity of the cases and may lead to overtreatment in some cases. On the other hand, the severity rating system by JRS GL 2008 seemed to be more accurate and closely correlated with the efficacy of the treatment. It is suggested that JRS GL 2008 is more useful in clinical practice for accurately judging the severity of the disease and initiating appropriate subsequent antibiotic therapy.
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Expression of gap junction protein connexin36 in multiple subtypes of GABAergic neurons in adult rat somatosensory cortex.
Cereb. Cortex
PUBLISHED: 04-05-2011
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To characterize connexin36 (Cx36)-expressing neurons of the adult rat somatosensory cortex, we examined fluorescence signals for Cx36 messenger RNA (mRNA) in 3 nonoverlapping subpopulations of ?-aminobutyric acid (GABA)ergic interneurons, which showed immunoreactivity for 1) parvalbumin (PV); 2) somatostatin (SOM); and 3) either calretinin (CR), vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), or choline acetyltransferase (ChAT). About 80% of PV-, 52% of SOM-, 37% of CR/VIP/CCK/ChAT-immunoreactive cells displayed Cx36 signals across all cortical layers, and inversely 64%, 25%, and 9% of Cx36-expressing neurons were positive for PV, SOM, or CR/VIP/CCK/ChAT, respectively. Notably, although almost all Cx36-expressing neurons in layer (L) 4, L5, and L6 were positive for one of these markers, a substantial proportion of those in L1 (91%) and L2/3 (10%) were negative for the markers tested, suggesting that other types of neurons might express Cx36. We further investigated the colocalization of Cx36 mRNA and ?-actinin2 immunoreactivity, as a marker for late-spiking GABAergic neurons, by using mirror-image sections. Surprisingly, more than 77% of ?-actinin2-positive cells displayed Cx36 signals in L1-L3, and about 49% and 13% of Cx36-expressing neurons were positive for ?-actinin2 in L1 and L2/3, respectively. These findings suggest that all the subtypes of GABAergic interneurons might form gap junctions in the neocortex.
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Patterns of axonal collateralization of single layer V cortical projection neurons in the rat presubiculum.
J. Comp. Neurol.
PUBLISHED: 04-01-2011
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The presubiculum is one of the important regions of the parahippocampal area known to be responsible for processing and integrating spatial representation information. To understand better the functional roles played by the presubiculum, it is essential to elucidate how output signals from the presubiculum distribute to its target regions. In the present study, the axonal branching patterns of single pyramidal neurons in layer V of the rat presubiculum were investigated by using in vivo injection of a viral vector expressing membrane-targeted palmitoylation site-attached green fluorescent protein. We found that individual layer V neurons provide axonal branches to one or two cortical areas with one or more recurrent collaterals to the presubiculum. These neurons were classified into six types, based on their axonal collateralization pattern: neurons with axon branches to 1) both the retrosplenial granular cortex and the parasubiculum, 2) both the retrosplenial granular cortex and the subiculum, and 3) both the medial entorhinal area and the subiculum, and neurons with axonal branches terminating only in 4) the retrosplenial granular cortex, 5) the subiculum, and 6) the presubiculum. Types 1-5 also provide recurrent axons to the presubiculum. Our data demonstrate that layer V of the presubiculum consists of at least six types of cortical projection neurons with various patterns of axonal collateralization. These findings suggest that single presubicular layer V neurons may distribute information to one or two cortical areas participating in the neural circuitry of spatial representation and also send such information back to the presubiculum itself.
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Glucose-lowering effect of colestimide is associated with baseline HbA1c in type 2 diabetic patients with hypercholesterolemia.
Endocr. J.
PUBLISHED: 02-22-2011
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We previously reported that colestimide, an anion exchange resin, improved glycemic control in patients with type 2 diabetes. However, the factors associated with the decrease of HbA1c remain unclear. In present study, we retrospectively compared glycemic control between groups receiving colestimide (n=71), atorvastatin (n=99), pravastatin (n=85), and pitavastatin (n=95) until 3 months after the start of treatment. In the colestimide group, fasting plasma glucose decreased significantly from 169 ± 59 to 138 ± 29 mg/dL after 3 months (P<0.01), and glycated hemoglobin (HbA1c) declined from 8.1 ± 1.0% to 7.4 ± 0.8% (an 8% reduction, P<0.01). Fasting plasma glucose and HbA1c did not change in the pravastatin and pitavastatin groups. On the other hand, both parameters increased significantly in the atorvastatin group. Multivariate analysis revealed that baseline HbA1c was the main determinant of the decrease of HbA1c in the colestimide group while age, sex, BMI, and baseline lipid levels were not correlated with the effect of colestimide treatment. The decrease of HbA1c showed a positive correlation with baseline HbA1c (r=0.60, P<0.0001), and patients with a larger change of HbA1c (>8.4%) displayed a better response to colestimide. In conclusion, since patients with type 2 diabetes often have hyperlipidemia as well, colestimide therapy may have a clinically useful dual action in such patients. Baseline HbA1c has the most important independent influence on the glucose-lowering effect of colestimide.
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Exclusive and common targets of neostriatofugal projections of rat striosome neurons: a single neuron-tracing study using a viral vector.
Eur. J. Neurosci.
PUBLISHED: 02-15-2011
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The rat neostriatum has a mosaic organization composed of striosome/patch compartments embedded in a more extensive matrix compartment, which are distinguished from each other by the input-output organization as well as by the expression of many molecular markers. The matrix compartment gives rise to the dual ?-aminobutyric acid (GABA)ergic striatofugal systems, i.e. direct and indirect pathway neurons, whereas the striosome compartment is considered to involve direct pathway neurons alone. Although the whole axonal arborization of matrix striatofugal neurons has been examined in vivo by intracellular staining, that of striosome neurons has never been studied at the single neuron level. In the present study, the axonal arborizations of single striosome projection neurons in rat neostriatum were visualized in their entirety using a viral vector expressing membrane-targeted green fluorescent protein, and compared with that of matrix projection neurons. We found that not only matrix but also striosome compartments contained direct and indirect pathway neurons. Furthermore, only striatonigral neurons in the striosome compartment projected directly to the substantia nigra pars compacta (SNc), although they sent a substantial number of axon collaterals to the globus pallidus, entopeduncular nucleus and/or substantia nigra pars reticulata. These results suggest that striosome neurons play a more important role in the formation of reward-related signals of SNc dopaminergic neurons than do matrix neurons. Together with data from previous studies in the reinforcement learning theory, our results suggest that these direct and indirect striosome-SNc pathways together with nigrostriatal dopaminergic neurons may help striosome neurons to acquire the state-value function.
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Complementary distribution of glutamatergic cerebellar and GABAergic basal ganglia afferents to the rat motor thalamic nuclei.
Eur. J. Neurosci.
PUBLISHED: 11-14-2010
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Motor thalamic nuclei, ventral anterior (VA), ventral lateral (VL) and ventral medial (VM) nuclei, receive massive glutamatergic and GABAergic afferents from the cerebellum and basal ganglia, respectively. In the present study, these afferents were characterized with immunoreactivities for glutamic acid decarboxylase of 67 kDa (GAD67) and vesicular glutamate transporter (VGluT)2, and examined by combining immunocytochemistry with the anterograde axonal labeling and neuronal depletion methods in the rat brain. VGluT2 immunoreactivity was intense in the caudodorsal portion of the VA-VL, whereas GAD67 immunoreactivity was abundant in the VM and rostroventral portion of the VA-VL. The rostroventral VA-VL and VM contained two types of GAD67-immunopositive varicosities (large and small), but the caudodorsal VA-VL comprised small ones alone. VGluT2-immunopositive varicosities were much larger in the caudodorsal VA-VL than those in the rostroventral VA-VL and VM. When anterograde tracers were injected into the basal ganglia output nuclei, the vast majority of labeled axon varicosities were large and distributed in the rostroventral VA-VL and VM, showing immunoreactivity for GAD67, but not for VGluT2. Only the large GAD67-immunopositive varicosities were mostly abolished by kainic acid depletion of substantia nigra neurons. In contrast, large to giant axon varicosities derived from the deep cerebellar nuclei were distributed mostly in the caudodorsal VA-VL, displaying VGluT2 immunoreactivity. The VGluT2-positive varicosities disappeared from the core portion of the caudodorsal VA-VL by depletion of cerebellar nucleus neurons. Thus, complementary distributions of large VGluT2- and GAD67-positive terminals in the motor thalamic nuclei are considered to reflect glutamatergic cerebellar and GABAergic basal ganglia afferents, respectively.
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Expression pattern of enkephalinergic neurons in the developing spinal cord revealed by preproenkephalin-green fluorescent protein transgenic mouse and its colocalization with GABA immunoreactivity.
Cells Tissues Organs (Print)
PUBLISHED: 09-20-2010
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To gain better insight into the ontogenic function of enkephalin (ENK) in the spinal cord, it is necessary to have a clear picture of the developing pattern of the ENKergic neurons. To address this question, we used transgenic mice which reveal ENKergic neurons easily by expressing enhanced green fluorescent protein (GFP) under the specific transcriptional control of the preproenkephalin (PPE) gene. GFP-positive neurons first appeared at embryonic day (E) 11.5 in the ventromedial part of the cervical ventral gray matter. At E13, they were mainly present in the intermediate zone. Thereafter, GFP-positive neurons increased progressively in number and extended from ventral to dorsal regions. Quantitative analysis showed that GFP-positive neurons peaked in number at postnatal day (P) 7 at the cervical level. The number of GFP-positive neurons reached a peak at P3 at the lumbar level. At P21, the distribution pattern of GFP immunoreactivity was similar to that in the adult spinal cord. Double-labeling results showed that about one-third of the total ?-aminobutyric acid cell population colocalized with GFP: 34.9 ± 3.5% at E16 and 32.4 ± 3.7% at P3. Double-labeled neurons accounted for nearly half of the GFP-positive neurons: 42.4 ± 2.4% at E16 and 44.1 ± 2.9% at P3. Taken together, the present results suggest that ENKergic neurons develop according to a rostrocaudal and ventrodorsal gradient. These results have broad implications for understanding the functional roles of ENKergic neurotransmission in the developing spinal cord.
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The cellular expression of GABA(A) receptor alpha1 subunit during spermatogenesis in the mouse testis.
Histol. Histopathol.
PUBLISHED: 08-17-2010
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GABA(A) receptors are pentamers in structure and are mainly composed of alpha, beta and gamma subunits. These receptors are known to function as chloride channels. We observed alpha5, beta1 and gamma3 subunit immunoreactivity in the mouse testes, specifically in the cytoplasm surrounding the nucleus in the spermatocytes and spermatids. In the current study, alpha1 subunit immunoreactivity was located in the nucleus of spermatogonia, spermatocytes and round spermatids. Immunoelectron microscopy revealed that the alpha1 subunit was localized within the nucleus of pachytene and diplotene spermatocytes in the area of condensed chromatin rather than extended chromatin. Protein sequence analysis revealed that the alpha1 subunit included DM DNA binding domains that were related to transcription factors involved in testicular differentiation in adult mice. These findings suggest that the alpha1 subunit may undertake a gene transcription function during the maturation of germ cells. a1 immunoreactivity was also detected within the mitochondria of spermatocytes and in the acrosome of round and elongated spermatids. Although the precise physiological role of the GABA(A) receptor alpha1 subunit in mitochondria remains unknown, we hypothesize that its function in the acrosome may be related to the acrosome reaction during fertilization or during spermatogenesis.
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Dependence of beam broadening on detection angle in scanning transmission electron microtomography.
J Electron Microsc (Tokyo)
PUBLISHED: 06-29-2010
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It has been shown that scanning transmission electron microtomography (STEMT) is quite effective for observing specimens with thicknesses on the order of micrometers in three dimensions (3D). In STEMT, the specimen is scanned using a focused electron beam, and the electrons from the convergence point are detected at the detector placed at a certain detection angle. Until recently, a wide detection angle corresponding to the mode often called the dark-field (DF) mode was mainly used. Although the detection angle can vary and is one of the crucial experimental factors in STEMT, its effect on 3D reconstruction has never been discussed from either an experimental or a theoretical viewpoint. Moreover, the effectiveness of another mode of electron tomography, transmission electron microtomography (TEMT), is not clear. In the present study, a polymeric specimen, an acrylonitrile butadiene styrene resin, with a thickness of ~1 mum and a fixed volume was observed using three different modes, namely, TEMT, small detection-angle STEMT referred to as bright-field STEMT, and DF-STEMT, in order to examine their advantages and disadvantages by observing multiple scattering of electrons inside the specimen.
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Coexpression of VGLUT1 and VGLUT2 in trigeminothalamic projection neurons in the principal sensory trigeminal nucleus of the rat.
J. Comp. Neurol.
PUBLISHED: 06-10-2010
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VGLUT1 and VGLUT2 have been reported to show complementary distributions in most brain regions and have been assumed to define distinct functional elements. In the present study, we first investigated the expression of VGLUT1 and VGLUT2 in the trigeminal sensory nuclear complex of the rat by dual-fluorescence in situ hybridization. Although VGLUT1 and/or VGLUT2 mRNA signals were detected in all the nuclei, colocalization was found only in the principal sensory trigeminal nucleus (Vp). About 64% of glutamatergic Vp neurons coexpressed VGLUT1 and VGLUT2, and the others expressed either VGLUT1 or VGLUT2, indicating that Vp neurons might be divided into three groups. We then injected retrograde tracer into the thalamic regions, including the posteromedial ventral nucleus (VPM) and posterior nuclei (Po), and observed that the majority of both VGLUT1- and VGLUT2-expressing Vp neurons were retrogradely labeled with the tracer. We further performed anterograde labeling of Vp neurons and observed immunoreactivies for anterograde tracer, VGLUT1, and VGLUT2 in the VPM and Po. Most anterogradely labeled axon terminals showed immunoreactivities for both VGLUT1 and VGLUT2 in the VPM and made asymmetric synapses with dendritic profiles of VPM neurons. On the other hand, in the Po, only a few axon terminals were labeled with anterograde tracer, and they were positive only for VGLUT2. The results indicated that Vp neurons expressing VGLUT1 and VGLUT2 project to the VPM, but not to the Po, although the functional differences of three distinct populations of Vp neurons, VGLUT1-, VGLUT2-, and VGLUT1/VGLUT2-expressing ones, remain unsettled.
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Neurochemical features of enkephalinergic neurons in the mouse trigeminal subnucleus caudalis.
Neurochem. Int.
PUBLISHED: 04-25-2010
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Enkephalinergic (ENKergic) neurons have been proposed to play crucial roles in pain modulation in the trigeminal subnucleus caudalis (Vc). To assist an advance in the research of ENKergic neurons, here we used preproenkephalin-green fluorescent protein (PPE-GFP) transgenic mice, in which all ENKergic neurons were fluorescent. We first performed fluorescent in situ hybridization combined with immunofluorescent histochemistry to confirm the specificity of this transgenic mouse and its advantages in showing ENKergic neurons in the Vc. Then based on this useful transgenic mouse, we examined the phenotypic diversity of PPE-GFP neurons by immunostaining for several markers that characterize ENKergic neuron subtypes. About 25.9±1.9% of GFP-positive neurons were regarded as immunoreactive for glutamic acid decarboxylase (GAD)(67) mRNA and 14.7±1.4% of GFP-positive neurons were positive for ?-aminobutyric acid. The proportions of calbindin-, calretinin-positive cells among the ENKergic neurons were 8.4±1.2% and 7.3±1.7%, respectively. Only 1.1±0.1% of GFP-positive neurons colocalized with parvalbumin and no GFP-positive neurons were found to co-express neuronal nitric oxide synthase. We then injected retrograde tracer into the thalamic regions and observed that a small number of ENKergic neurons in the Vc were retrogradely labeled with the tracer. The present results provide a detailed morphological evidence of the neurochemical features of ENKergic neurons. These results have broad implications for understanding the functional roles of ENKergic neurotransmission in the Vc.
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Protein kinase G dynamically modulates TASK1-mediated leak K+ currents in cholinergic neurons of the basal forebrain.
J. Neurosci.
PUBLISHED: 04-23-2010
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Leak K(+) conductance generated by TASK1/3 channels is crucial for neuronal excitability. However, endogenous modulators activating TASK channels in neurons remained unknown. We previously reported that in the presumed cholinergic neurons of the basal forebrain (BF), activation of NO-cGMP-PKG (protein kinase G) pathway enhanced the TASK1-like leak K(+) current (I-K(leak)). As 8-Br-cGMP enhanced the I-K(leak) mainly at pH 7.3 as if changing the I-K(leak) from TASK1-like to TASK3-like current, such an enhancement of the I-K(leak) would result either from an enhancement of hidden TASK3 component or from an acidic shift in the pH sensitivity profile of TASK1 component. In view of the report that protonation of TASK channel decreases its open probability, the present study was designed to examine whether the activation of PKG increases the conductance of TASK1 channels by reducing their binding affinity for H(+), i.e., by increasing K(d) for protonation, or not. We here demonstrate that PKG activation and inhibition respectively upregulate and downregulate TASK1 channels heterologously expressed in PKG-loaded HEK293 cells at physiological pH, by causing shifts in the K(d) in the acidic and basic directions, respectively. Such PKG modulations of TASK1 channels were largely abolished by mutating pH sensor H98. In the BF neurons that were identified to express ChAT and TASK1 channels, similar dynamic modulations of TASK1-like pH sensitivity of I-K(leak) were caused by PKG. It is strongly suggested that PKG activation and inhibition dynamically modulate TASK1 currents at physiological pH by bidirectionally changing K(d) values for protonation of the extracellular pH sensors of TASK1 channels in cholinergic BF neurons.
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Choroidal metastasis with adenocarcinoma of the lung treated with gefitinib.
Eur J Ophthalmol
PUBLISHED: 04-13-2010
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To report a case of bilateral regression of choroidal metastasis with adenocarcinoma of the lung treated with gefitinib.
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Neurochemical properties of enkephalinergic neurons in lumbar spinal dorsal horn revealed by preproenkephalin-green fluorescent protein transgenic mice.
J. Neurochem.
PUBLISHED: 03-29-2010
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Enkephalin (ENK) has been implicated in nociceptive transmission in the spinal cord while its functional role is not clear because of difficulties in ideally visualizing ENKergic neurons. We thus developed preproenkephalin-green fluorescent protein transgenic mice to better identify ENKergic neurons. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) together with immunohistochemistry and in situ hybridization were first employed to confirm the successful transgenic manipulation and its application in showing spinal ENKergic neurons. The proportions of ENKergic neurons in the spinal cord laminae I, II, III and IV-VI among dorsal horn neurons were 15.8 +/- 3.1%, 39.5 +/- 3.3%, 11.8 +/- 1.9% and 10.7 +/- 2.1%, respectively. Double labeling with other molecules was then performed to further clarify the neurochemical properties of spinal ENKergic neurons. GABA was found to exist in 42.9 +/- 2.8% of ENKergic neurons that were mainly located in lamina I-III. The proportions of parvalbumin-, calretinin-, calbindin- and neuronal nitric oxide synthase-positive cells among the ENKergic neurons were 5.2 +/- 0.7%, 42.6 +/- 2.3%, 25.8 +/- 2.2% and 11.1 +/- 1.6%, respectively. Compared with previously findings obtained with ENK antibody labeling, this line of newly generated mice can be a reliable tool for the study of specific spinal ENKergic neuronal population.
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[Novel method for the single-cell structural analysis of neuronal processes--labeling with viral vectors].
Brain Nerve
PUBLISHED: 03-20-2010
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Novel methods for Golgi-stain-like labeling of neurons have been developed by applying molecular biological techniques. Using replication-deficient adenovirus and Sindbis viral vectors expressing membrane-targeted green fluorescent protein (GFP), we visualized the neuronal processes of the infected neurons completely. Furthermore, when sufficiently diluted Sindbis virus solution was injected into the brain, the entire axonal arborization of infected neurons was recovered at a single cell level, giving new insights into neuronal networks. We have also developed the dendritic membrane-targeted GFP by using lentiviral vectors with a neuron-specific promoter. When the dendritic membrane-targeted GFP was applied to the transgenic animal production, the information input site, i.e., the dendrites, of a specific neuron group was visualized perfectly. Since neuronal processes, axons and dendrites, are key structures of neuronal information processing, the molecular biological techniques introduced here are useful for the morphological analysis of neuronal networks and thus helpful for understanding the functional design of the nervous system.
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Hydroxyurea as an inhibitor of hepatitis C virus RNA replication.
Arch. Virol.
PUBLISHED: 03-05-2010
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Hepatitis C virus (HCV) is the main causative agent of chronic liver disease, which may develop into liver cirrhosis and hepatocellular carcinoma. By using a recently developed reporter assay system in which genome-length HCV RNA replicates efficiently, we found that hydroxyurea (HU), a DNA synthesis inhibitor, inhibited HCV RNA replication. Moreover, we demonstrated that the anti-HCV activity of the combination of IFN-alpha and HU was higher than that of IFN-alpha alone. These results suggest that HU may be an effective anti-HCV reagent that can be used not only singly but also in combination with IFN-alpha to treat chronic hepatitis C.
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Reduced expression of claudin-7 is associated with poor outcome in non-small cell lung cancer.
Oncol Lett
PUBLISHED: 03-02-2010
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Claudin-7 is a tight junction protein that plays an important role in tumorigenesis, tumor invasion and metastasis. We examined the clinical significance of claudin-7 expression in 75 postsurgical non-small cell lung cancer (NSCLC) patients. Claudin-7 expression was measured immunohistochemically and was found to be high in 25 patients (33.3%) and low in 50 (66.7%). Survival was significantly poorer in patients with claudin-7-low than in those with claudin-7-high NSCLCs (P=0.024). In particular, survival was significantly poorer in patients with claudin-7-low than in those with claudin-7-high squamous cell carcinomas (P=0.011). A reduced expression of claudin-7 was associated with poor outcome in NSCLCs. Claudin-7 may thus be a useful biomarker and a potential therapeutic target in patients with NSCLC.
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Corticofugal control of vibrissa-sensitive neurons in the interpolaris nucleus of the trigeminal complex.
J. Neurosci.
PUBLISHED: 02-05-2010
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Trigeminal sensory nuclei that give rise to ascending pathways of vibrissal information are heavily linked by intersubnuclear connections. This is the case, for instance, of the principal trigeminal nucleus, which receives strong inhibitory input from the caudal sector of the interpolaris subnucleus. Because this inhibitory input can gate the relay of sensory messages through the lemniscal pathway, a central issue in vibrissal physiology is how brain regions that project to the interpolaris control the activity of inhibitory cells. In the present study, we examined how corticotrigeminal neurons of the primary and second somatosensory cortical areas control the excitability of interpolaris cells. Results show that these two cortical areas exert a differential control over the excitability of projection cells and intersubnuclear interneurons, and that this control also involves the recruitment of inhibitory cells in the caudalis subnucleus. These results provide a basic circuitry for a mechanism of disinhibition through which the cerebral cortex can control the relay of sensory messages in the lemniscal pathway. It is proposed that top-down control of brainstem circuits is prompted by motor strategies, expectations, and motivational states of the animal.
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High frequency of ?-lactamase-negative, ampicillin-resistant strains of Haemophilus influenzae in patients with chronic bronchitis in Japan.
J. Infect. Chemother.
PUBLISHED: 01-16-2010
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In Japan, the increasing incidence of ?-lactum-resistant Haemophilus influenzae infections is of growing concern. We retrospectively studied whether the prevalence of ?-lactamase-negative ampicillin-resistant strains of H. influenzae was influenced by chronic lung diseases. H. influenzae isolates, obtained from patients who were diagnosed with acute or chronic bronchitis, or acute exacerbation of chronic bronchitis in 2005, were studied. In addition to susceptibility testing, polymerase chain reaction (PCR) was performed for the detection of TEM-1 ?-lactamase, and Asn526-Lys and Ser385-Thr amino acid substitutions in the ftsI gene encoding penicillin-binding protein-3 (PBP-3). The minimum inhibitory concentration values of ?-lactams were found to be increased in isolates from patients with chronic bronchitis who had been repeatedly administered antibiotics. Genetic analysis using PCR suggested that this might be associated with a high frequency of ?-lactamase-negative strains with mutations in PBP-3. The presence of ?-lactum-resistant strains needs to be considered for patients with chronic bronchitis in whom H. influenzae is isolated as a causative pathogen.
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Armadillo Repeat Containing 8alpha Binds to HRS and Promotes HRS Interaction with Ubiquitinated Proteins.
Open Biochem J
PUBLISHED: 01-13-2010
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Recently, we reported that a complex with an essential role in the degradation of Fructose-1,6-bisphosphatase in yeast is well conserved in mammalian cells; we named this mammalian complex C-terminal to the Lissencephaly type-1-like homology (CTLH) complex. Although the function of the CTLH complex remains unclear, here we used yeast two-hybrid screening to isolate Hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) as a protein binding to a key component of CTLH complex, Armadillo repeat containing 8 (ARMc8) alpha. The association was confirmed by a yeast two-hybrid assay and a co-immunoprecipitation assay. The proline-rich domain of HRS was essential for the association. As demonstrated through immunofluorescence microscopy, ARMc8alpha co-localized with HRS. ARMc8alpha promoted the interaction of HRS with various ubiquitinated proteins through the ubiquitin-interacting motif. These findings suggest that HRS mediates protein endosomal trafficking partly through its interaction with ARMc8alpha.
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A case of Poncets disease (tuberculous rheumatism).
Rheumatol. Int.
PUBLISHED: 09-25-2009
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We describe a 37-year-old woman with recurrent polyarthritis, and recurrent erythema nodosum on the flexible side of her left forearm. On an X-ray of the chest, infiltration of the right upper lobe was observed. Transcription-reverse transcription concerted reaction in sputum samples revealed Mycobacterium tuberculosis (M. tuberculosis). Resolution of the polyarthritis with anti-tuberculosis (TB) drugs occurred in 3 days. We diagnosed her with Poncets disease (PD). PD is considered to be a reactive arthritis, which is a different entity from tuberculous arthritis. Although PD is a rare disease, we should be aware of it as one of the differential diagnoses, even in patients without typical symptoms of TB.
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Ischemia-induced neurogenesis of neocortical layer 1 progenitor cells.
Nat. Neurosci.
PUBLISHED: 08-26-2009
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Adult mammalian neurogenesis occurs in the hippocampus and the olfactory bulb, whereas neocortical adult neurogenesis remains controversial. Several occurrences of neocortical adult neurogenesis in injured neocortex were recently reported, suggesting that neural stem cells (NSCs) or neuronal progenitor cells (NPCs) that can be activated by injury are maintained in the adult brain. However, it is not clear whether or where neocortical NSCs/NPCs exist in the brain. We found NPCs in the neocortical layer 1 of adult rats and observed that their proliferation was highly activated by global forebrain ischemia. Using retrovirus-mediated labeling of layer 1 proliferating cells with membrane-targeted green fluorescent protein, we found that the newly generated neurons were GABAergic and that the neurons were functionally integrated into the neuronal circuitry. Our results suggest that layer 1 NPCs are a source of adult neurogenesis under ischemic conditions.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.