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1. Case report: Corneal endothelial degeneration and optic atrophy in dentatorubral-pallidoluysian atrophy quantified by specular micrography and optical coherence tomography

Author

Shunya Takizawa, Hiroto Mitamura, Yuko Ohnuki, Kenji Kawai, Yoichi Ohnuki, Eiichiro Nagata, and Wakoh Takahashi

Subjects
CAG repeat, corneal endothelial degeneration, dentatorubral-pallidoluysian atrophy, optical coherence tomography, specular micrography, Neurology. Diseases of the nervous system, RC346-429
Abstract

IntroductionDentatorubral-pallidoluysian atrophy (DRPLA) is an autosomal dominant neurodegenerative disease with various neurological manifestations. Corneal endothelial degeneration and optic atrophy have been reported separately; however, there are no reports of corneal endothelial degeneration with optic atrophy.CasesHerein, we present four related patients with DRPLA: two patients (69-year-old woman and 80-year-old man) who exhibited both corneal endothelial degeneration and optic atrophy and another two (49- and 51-year-old women, respectively) who exhibited only corneal endothelial degeneration. We quantified the reduction in corneal endothelial cell density (ECD) and hexagonality using specular microscopy and thinning of the circumpapillary retinal nerve fiber layer (RNFL) using optical coherence tomography (OCT).ConclusionThis is the first report of DRPLA accompanied by corneal endothelial degeneration and/or optic atrophy, which were both quantified based on the corneal ECD and the circumpapillary RNFL thickness using specular micrography and OCT, respectively. The pathophysiological mechanism is unclear; however, the involvement of the nuclear receptor TLX interacting with atrophin-1 may be implicated in ophthalmic manifestations of DRPLA. Therefore, we recommend performing specular micrography and/or OCT when patients with DRPLA experience visual disturbances.

Published
2022
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2. Dysregulation of post-transcriptional modification by copy number variable microRNAs in schizophrenia with enhanced glycation stress

Author

Akane Yoshikawa, Itaru Kushima, Mitsuhiro Miyashita, Kazuya Toriumi, Kazuhiro Suzuki, Yasue Horiuchi, Hideya Kawaji, Shunya Takizawa, Norio Ozaki, Masanari Itokawa, and Makoto Arai

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Previously, we identified a subpopulation of schizophrenia (SCZ) showing increased levels of plasma pentosidine, a marker of glycation and oxidative stress. However, its causative genetic factors remain largely unknown. Recently, it has been suggested that dysregulated posttranslational modification by copy number variable microRNAs (CNV-miRNAs) may contribute to the etiology of SCZ. Here, an integrative genome-wide CNV-miRNA analysis was performed to investigate the etiology of SCZ with accumulated plasma pentosidine (PEN-SCZ). The number of CNV-miRNAs and the gene ontology (GO) in the context of miRNAs within CNVs were compared between PEN-SCZ and non-PEN-SCZ groups. Gene set enrichment analysis of miRNA target genes was further performed to evaluate the pathways affected in PEN-SCZ. We show that miRNAs were significantly enriched within CNVs in the PEN-SCZ versus non-PEN-SCZ groups (p = 0.032). Of note, as per GO analysis, the dysregulated neurodevelopmental events in the two groups may have different origins. Additionally, gene set enrichment analysis of miRNA target genes revealed that miRNAs involved in glycation/oxidative stress and synaptic neurotransmission, especially glutamate/GABA receptor signaling, were possibly affected in PEN-SCZ. To the best of our knowledge, this is the first genome-wide CNV-miRNA study suggesting the role of CNV-miRNAs in the etiology of PEN-SCZ, through effects on genes related to glycation/oxidative stress and synaptic function. Our findings provide supportive evidence that glycation/oxidative stress possibly caused by genetic defects related to the posttranscriptional modification may lead to synaptic dysfunction. Therefore, targeting miRNAs may be one of the promising approaches for the treatment of PEN-SCZ.

Published
2021
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3. AKR1A1 Variant Associated With Schizophrenia Causes Exon Skipping, Leading to Loss of Enzymatic Activity

Author

Kyoka Iino, Kazuya Toriumi, Riko Agarie, Mitsuhiro Miyashita, Kazuhiro Suzuki, Yasue Horiuchi, Kazuhiro Niizato, Kenichi Oshima, Atsushi Imai, Yukihiro Nagase, Itaru Kushima, Shinsuke Koike, Tempei Ikegame, Seiichiro Jinde, Eiichiro Nagata, Shinsuke Washizuka, Toshio Miyata, Shunya Takizawa, Ryota Hashimoto, Kiyoto Kasai, Norio Ozaki, Masanari Itokawa, and Makoto Arai

Subjects
aldo-keto reductase family 1 member A1, treatment-resistant schizophrenia, single nucleotide variant (SNV), exon skipping, frameshift mutation, glucuronate, Genetics, QH426-470
Abstract

Schizophrenia is a heterogeneous psychiatric disorder characterized by positive symptoms such as hallucinations and delusions, negative symptoms such as anhedonia and flat affect, and cognitive impairment. Recently, glucuronate (GlucA) levels were reported to be significantly higher in serum of patients with schizophrenia than those in healthy controls. The accumulation of GlucA is known to be related to treatment-resistant schizophrenia, since GlucA is known to promote drug excretion by forming conjugates with drugs. However, the cause of GlucA accumulation remains unclear. Aldo-keto reductase family one member A1 (AKR1A1) is an oxidoreductase that catalyzes the reduction of GlucA. Genetic loss of AKR1A1 function is known to result in the accumulation of GlucA in rodents. Here, we aimed to explore genetic defects in AKR1A1 in patients with schizophrenia, which may result in the accumulation of GlucA. We identified 28 variants of AKR1A1 in patients with schizophrenia and control subjects. In particular, we identified a silent c.753G > A (rs745484618, p. Arg251Arg) variant located at the first position of exon 8 to be associated with schizophrenia. Using a minigene assay, we found that the c.753G > A variant induced exon 8 skipping in AKR1A1, resulting in a frameshift mutation, which in turn led to truncation of the AKR1A1 protein. Using the recombinant protein, we demonstrated that the truncated AKR1A1 completely lost its activity. Furthermore, we showed that AKR1A1 mRNA expression in the whole blood cells of individuals with the c.753G > A variant tended to be lower than that in those without the variants, leading to lower AKR activity. Our findings suggest that AKR1A1 carrying the c.753G > A variant induces exon skipping, leading to a loss of gene expression and enzymatic activity. Thus, GlucA patients with schizophrenia with the c.753G > A variant may show higher GlucA levels, leading to drug-resistant schizophrenia, since drug excretion by GlucA is enhanced.

Published
2021
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4. Effect of early enteral nutrition on critical care outcomes in patients with acute ischemic stroke

Author

Atsushi Mizuma, Shizuka Netsu, Masaki Sakamoto, Sachiko Yutani, Eiichiro Nagata, and Shunya Takizawa

Subjects
Medicine (General), R5-920
Abstract

Objective Stroke-associated pneumonia (SAP) is a comorbidity of ischemic stroke related to clinical outcomes. Early enteral nutrition (EEN; within 48 hours) reduces the incidence of infection and length of intensive care unit (ICU)/hospital stay. The relationship between EEN and critical care outcomes, including SAP, in patients with ischemic stroke has been insufficiently studied. Methods We recruited 499 patients in this retrospective observational study. We evaluated SAP incidence within 14 days from admission. Patients were divided into an EEN group and a late EN group (LEN; start later than EEN). We compared groups regarding background and length of ICU/hospital stay. Results EN was started within 48 hours in 236 patients. SAP was diagnosed in 94 patients (18.8%), with most in the LEN group (28.1% vs. 8.5%). Median [interquartile range] lengths of hospitalization (22 [12–30] days vs. 35 [20–45] days) and ICU stay (4 [2–5] days vs. 6 [3–8] days) were longer in the LEN group. EEN reduced the incidence of SAP. By contrast, consciousness disturbance and worsening consciousness level increased the SAP incidence. Increased age and National Institutes of Health Stroke Scale score were associated with start of prolonged EN. Conclusions We found that EEN may reduce SAP risk.

Published
2021
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5. Advanced glycation end products and cognitive impairment in schizophrenia.

Author

Akiko Kobori, Mitsuhiro Miyashita, Yasuhiro Miyano, Kazuhiro Suzuki, Kazuya Toriumi, Kazuhiro Niizato, Kenichi Oshima, Atsushi Imai, Yukihiro Nagase, Akane Yoshikawa, Yasue Horiuchi, Syudo Yamasaki, Atsushi Nishida, Satoshi Usami, Shunya Takizawa, Masanari Itokawa, Heii Arai, and Makoto Arai

Subjects
Medicine, Science
Abstract

Advanced glycation end products play a key role in the pathophysiology of schizophrenia. Cognitive impairment is one of the central features of schizophrenia; however, the association between advanced glycation end products and cognitive impairment remains unknown. This study investigated whether advanced glycation end products affect the cognitive domain in patients with schizophrenia. A total of 58 patients with chronic schizophrenia were included in this cross-sectional study. Plasma advanced glycation end products were measured using high-performance liquid chromatography (HPLC). Neuropsychological and cognitive functions were assessed using the Wechsler Adult Intelligence Scale, Third Version, and the Wisconsin Card Sorting Test Keio-FS version. Multiple regression analysis adjusted for age, sex, body mass index, educational years, daily dose of antipsychotics, and psychotic symptoms revealed that processing speed was significantly associated with plasma pentosidine, a representative advanced glycation end product (standardized β = -0.425; p = 0.009). Processing speed is the cognitive domain affected by advanced glycation end products. Considering preceding evidence that impaired processing speed is related to poor functional outcome, interventions targeted at reducing advanced glycation end products may contribute to promoting recovery of patients with schizophrenia as well as cognitive function improvement.

Published
2021
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6. A case of recurrent Mikulicz’s disease with mononeuritis multiplex

Author

Atsushi Mizuma, Maiko Kouchi, Chikage Kijima, Sachiko Yutani, Tsuyoshi Uesugi, Eiichiro Nagata, and Shunya Takizawa

Subjects
Mikulicz’s disease, mononeuritis multiplex, IgG4, steroid therapy, Medicine
Abstract

We report an 82-year-old man with recurrence of Mikulicz’s disease accompanied with mononeuritis multiplex. On admission, both upper eyelids, the salivary gland, the dorsum of the left hand and both legs were swollen. Neurological examination showed motor weakness of distal limbs (manual muscle testing 3/5) and decreased touch, pain and vibration sensation of the dorsum of the left hand and both legs. Deep tendon reflex in both legs was also decreased. We diagnosed Mikulicz’s disease based on high serum immunoglobulin (Ig)G4 (630 mg/dl, 26.1% of total IgG) and lacrimal gland biopsy findings. Clinical symptoms and motor conduction study findings improved after steroid therapy. However, tapering of the steroid dose resulted in recurrence two years later. Steroid therapy is usually effective for IgG4-related neuropathy, and we found that an increase of steroid dose was effective to treat the recurrence. But, in general, a suitable maintenance dose of steroid in combination with an immunosuppressant may be necessary to prevent relapse.

Published
2018
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7. A Case of Suspected Breast Cancer Metastasis to Brachial Plexus Detected by Magnetic Resonance Neurography

Author

Atsushi Mizuma, Chikage Kijima, Eiichiro Nagata, and Shunya Takizawa

Subjects
Magnetic resonance neurography, Brachial plexus, Breast cancer, Metastasis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Metastasis of breast cancer is often detected through a long-term course and difficult to diagnose. We report a case of brachial plexopathy suspected to be the initial lesion of breast cancer metastasis, which was only detected by magnetic resonance (MR) neurography. A 61-year-old woman was admitted to our hospital within 2 years after operation for breast cancer because of progressive dysesthesia and motor weakness initially in the upper limb on the affected side and subsequently on the contralateral side. Enhanced computed tomography, axillary lymph node echo, gallium scintigraphy, and short tau inversion recovery MR images showed no abnormalities. MR neurography revealed a swollen region in the left brachial plexus. We suspected neuralgic amyotrophy and initiated treatment with intravenous immunoglobulin therapy and steroid therapy. However, there was no improvement, and the progression of motor weakness in the bilateral lower limbs appeared over 4 years. Concomitant elevation of carbohydrate antigen 15-3 level (58.9 U/ml) led us to suspect breast cancer metastasis, which was associated with the worsening of neurological findings, although gallium scintigraphy and bone scintigraphy showed no inflammatory and metastatic lesions. Swelling of the cauda equina in enhanced lumbar MR imaging and abnormal accumulation at the brachial plexus and cervical spinal cord in positron-emission tomography were newly detected contrary to the normal findings on the gallium scintigraphy, which suggested cerebrospinal fluid seeding. We suspected breast cancer metastasis about the initial brachial plexopathy based on the clinical course. MR neurography may be a helpful tool to detect metastatic lesion, especially in nerve roots.

Published
2016
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8. Prior Anticoagulation and Short‐ or Long‐Term Clinical Outcomes in Ischemic Stroke or Transient Ischemic Attack Patients With Nonvalvular Atrial Fibrillation

Author

Keisuke Tokunaga, Masatoshi Koga, Ryo Itabashi, Hiroshi Yamagami, Kenichi Todo, Sohei Yoshimura, Kazumi Kimura, Shoichiro Sato, Tadashi Terasaki, Manabu Inoue, Yoshiaki Shiokawa, Masahito Takagi, Kenji Kamiyama, Kanta Tanaka, Shunya Takizawa, Masayuki Shiozawa, Satoshi Okuda, Yasushi Okada, Tomoaki Kameda, Yoshinari Nagakane, Yasuhiro Hasegawa, Satoshi Shibuya, Yasuhiro Ito, Hideki Matsuoka, Kazuhiro Takamatsu, Kazutoshi Nishiyama, Kazuomi Kario, Yoshiki Yagita, Kyohei Fujita, Daisuke Ando, Masaya Kumamoto, Shoji Arihiro, and Kazunori Toyoda

Subjects
anticoagulation, atrial fibrillation, ischemic stroke, outcome, transient ischemic attack, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background We aimed to clarify associations between prior anticoagulation and short‐ or long‐term clinical outcomes in ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation. Methods and Results A total of 1189 ischemic stroke or transient ischemic attack patients with nonvalvular atrial fibrillation who were hospitalized within 7 days after onset were analyzed. Of these, 813 patients (68.4%) received no prior anticoagulation, 310 (26.1%) received prior warfarin treatment with an international normalized ratio (INR)

Published
2019
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9. Regeneration-associated cell transplantation contributes to tissue recovery in mice with acute ischemic stroke.

Author

Taira Nakayama, Eiichiro Nagata, Haruchika Masuda, Takayuki Asahara, and Shunya Takizawa

Subjects
Medicine, Science
Abstract

Various cell-based therapeutic strategies have been investigated for vascular and tissue regeneration after ischemic stroke. We have developed a novel cell population, called regeneration-associated cells (RACs), by quality- and quantity-controlled culture of unfractionated mononuclear cells. RACs were trans-arterially injected into 10-week-old syngeneic male mice at 1, 3, 5 or 7 days after permanent middle cerebral artery occlusion (MCAO) to determine the optimal timing for administration in terms of outcome at day 21. Next, we examined the effects of RACs injection at day 1 after MCAO on neurological deficits, infarct volume, and mediators of vascular regeneration and anti-inflammation at days 7 and 21. Infarct volume at day 21 was significantly reduced by transplantation of RACs at day 1 or 3. RACs injected at day 1 reduced the infarct volume at day 7 and 21. Angiogenesis and anti-inflammatory mediators, VEGF and IL-10, were increased at day 7, and VEGF was still upregulated at day 21. We also observed significantly enhanced ink perfusion in vivo, tube formation in vitro, and definitive endothelial progenitor cell colonies in colony assay. These results suggest that RAC transplantation in MCAO models promoted significant recovery of neural tissues through intensified anti-inflammatory and angiogenic effects.

Published
2019
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10. Serum apolipoprotein E may be a novel biomarker of migraine.

Author

Naoki Yuasa, Eiichiro Nagata, Natsuko Fujii, Masatoshi Ito, Hideo Tsukamoto, and Shunya Takizawa

Subjects
Medicine, Science
Abstract

Migraine attacks alter various molecules that might be related to the pathophysiology of migraine, such as serotonin, calcitonin gene-related peptide, and nitric oxide. The underlying pathophysiology of migraine is as yet unclear. We explored key proteins related to the pathogenesis of migraine here. Serum was collected from two patients with migraine with aura (MA) and seven patients with migraine without aura (MO) during attack-free periods and migraine attacks. Samples were analyzed using 2-dimensional gel electrophoresis. Nineteen protein spots were altered between the attack-free versus migraine attack periods. Mass spectrometric analysis was performed to identify the proteins within each of the 19 altered spots. Thirty-six proteins were significantly altered in samples collected during attack-free periods versus migraine attacks. The protein with the statistically most significant MASCOT/Mowse score (268±112) among lipoproteins was apolipoprotein (ApoE). In the MA and MO groups, ApoE protein levels were significantly higher during migraine attack than during the attack-free period (p

Published
2018
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12. Possible association between dysfunction of vitamin D binding protein (GC Globulin) and migraine attacks.

Author

Eiichiro Nagata, Natsuko Fujii, Kazuyoshi Hosomichi, Shigeki Mitsunaga, Yoichi Suzuki, Yoichi Mashimo, Hideo Tsukamoto, Tadayuki Satoh, Motoki Osawa, Ituro Inoue, Akira Hata, and Shunya Takizawa

Subjects
Medicine, Science
Abstract

To identify the genetic causality of migraine and acute, severe melalgia, we performed a linkage analysis and exome sequencing in a family with four affected individuals. We identified a variant (R21L) in exon 2 of the GC globulin gene, which is involved in the transportation of vitamin D metabolites and acts as a chemotaxic factor; this variant was co-segregated within the family. To investigate the relationship between GC globulin and melalgia, we investigated the cytokine levels in serum samples from the patients and control subjects using a cytokine antibody array. GC globulin can bind to both MCP-1 and RANTES in human serum but has a higher affinity to MCP-1. In cell culture systems, MCP-1 was able to bind to overexpressed wild-type GC globulin but not to the GC globulin variant, and the GC globulin binding affinity to MCP-1 was significantly lower in sera from the patients than in sera from control subjects. A higher concentration of MCP-1 was also observed in sera from the patients. Thus, the dysfunctional GC globulin affected cytokine release, especially the release of MCP-1, and MCP-1 might play important roles in melalgia and migraine.

Published
2014
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13. Low-Dose Intravenous Alteplase in Wake-Up Stroke

Author

Kazunori Toyoda, Yusuke Yakushiji, Shuichi Igarashi, Yoshiaki Shiokawa, Toshimitsu Hamasaki, Ryosuke Doijiri, Shinichi Yoshimura, Masafumi Ihara, Hideyuki Ohnishi, Kaori Miwa, Yoshikazu Uesaka, Haruko Yamamoto, Yasushi Takagi, Masato Osaki, Ryo Itabashi, Junya Aoki, Rei Kondo, Taizen Nakase, Takao Urabe, Akira Tsujino, Kazumi Kimura, Takanari Kitazono, Yasuhiro Ito, Takao Kanzawa, Sohei Yoshimura, Shunya Takizawa, Kazuo Minematsu, Takeshi Inoue, Yoshinari Nagakane, Akira Oita, Yasuhiro Hasegawa, Kenji Kamiyama, Masafumi Ohtaki, Toru Iwama, Toshihiro Ueda, Makoto Sasaki, Nobuyuki Sakai, Koko Asakura, Masatoshi Koga, Manabu Inoue, Yasushi Okada, and Mayumi Fukuda-Doi

Subjects
control groups, stroke, acute, medicine.medical_treatment, intracranial hemorrhages, law.invention, Randomized controlled trial, law, Modified Rankin Scale, medicine, magnetic resonance imaging, Stroke, tissue-type plasminogen activator, Advanced and Specialized Nursing, medicine.diagnostic_test, business.industry, Standard treatment, informed consent, Magnetic resonance imaging, Thrombolysis, medicine.disease, Hyperintensity, Relative risk, Anesthesia, Neurology (clinical), Cardiology and Cardiovascular Medicine, business
Abstract

Background and Purpose— We assessed whether lower-dose alteplase at 0.6 mg/kg is efficacious and safe for acute fluid-attenuated inversion recovery-negative stroke with unknown time of onset. Methods— This was an investigator-initiated, multicenter, randomized, open-label, blinded-end point trial. Patients met the standard indication criteria for intravenous thrombolysis other than a time last-known-well >4.5 hours (eg, wake-up stroke). Patients were randomly assigned (1:1) to receive alteplase at 0.6 mg/kg or standard medical treatment if magnetic resonance imaging showed acute ischemic lesion on diffusion-weighted imaging and no marked corresponding hyperintensity on fluid-attenuated inversion recovery. The primary outcome was a favorable outcome (90-day modified Rankin Scale score of 0–1). Results— Following the early stop and positive results of the WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke), this trial was prematurely terminated with 131 of the anticipated 300 patients (55 women; mean age, 74.4±12.2 years). Favorable outcome was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk [RR], 0.97 [95% CI, 0.68–1.41]; P =0.892). Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity [95% CI, 0.06 to infinity]; P >0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 [95% CI, 0.06–12.58]; P >0.999), respectively. Conclusions— No difference in favorable outcome was seen between alteplase and control groups among patients with ischemic stroke with unknown time of onset. The safety of alteplase at 0.6 mg/kg was comparable to that of standard treatment. Early study termination precludes any definitive conclusions. Registration— URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02002325.

Published
2020

14. Insufficient production of IL-10 from M2 macrophages impairs in vitro endothelial progenitor cell differentiation in patients with Moyamoya disease

Author

Taira Nakayama, Haruchika Masuda, Shunya Takizawa, Takatoshi Sorimachi, Eiichiro Nagata, Ryoko Imazeki, Takayuki Asahara, Shizuka Netsu, Hiroko Yuzawa, Mitsunori Matsumae, Natsuko Fujii, Saori Kohara, and Takahiro Osada

Subjects
0301 basic medicine, Adult, Male, Cell, Cell Culture Techniques, Down-Regulation, lcsh:Medicine, Peripheral blood mononuclear cell, Endothelial progenitor cell, Article, Flow cytometry, Pathogenesis, Colony-Forming Units Assay, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, medicine, Humans, Author Correction, lcsh:Science, Cells, Cultured, Endothelial Progenitor Cells, Multidisciplinary, medicine.diagnostic_test, business.industry, Macrophages, lcsh:R, Cell Differentiation, Middle Aged, Flow Cytometry, Interleukin-10, Stroke, Interleukin 10, 030104 developmental biology, medicine.anatomical_structure, Cell culture, Case-Control Studies, Cancer research, Leukocytes, Mononuclear, Tetradecanoylphorbol Acetate, Female, lcsh:Q, Moyamoya Disease, business, 030217 neurology & neurosurgery, Cell signalling
Abstract

Moyamoya disease (MMD) is well known to be caused by insufficient cerebral vascular formation. However, the essential pathogenesis has not yet been identified. Using our recently developed technique of generating vasculogenic and anti-inflammatory cultures, we investigated endothelial progenitor cell (EPC) expansion and differentiation under the cytokine milieu generated by the peripheral blood mononuclear cells (PBMNCs) of the operated and non-operated MMD patients. EPC colony forming assay of the cultured PBMNCs disclosed the decline of the definitive EPC colony numbers in the both MMD patients. The level of interleukin-10 (IL-10) was lower in secretory cytokines from the cultured PBMNCs of MMD patients than that in that of controls using a cytometric bead array. The addition of human recombinant IL-10 to PBMNCs cultured from MMD patients restored the EPC colony forming potential of MMD PBMNCs. Following phorbol myristate acetate stimulation of the cultured PBMNCs, flow cytometry revealed a decrease in intracellular IL-10 storage in the main cell populations of the PBMNCs cultured from MMD patients relative to those cultured from controls. The present data provide the expected mechanism of vascular malformation in MMD pathogenesis originated from the insufficient production of IL-10 secreting cells from PBMNCs fostering EPC expansion and differentiation.

Published
2019
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15. Advanced glycation end products and cognitive impairment in schizophrenia

Author

Kazuhiro Suzuki, Satoshi Usami, Yasuhiro Miyano, Makoto Arai, Kenichi Oshima, Akane Yoshikawa, Syudo Yamasaki, Shunya Takizawa, Yukihiro Nagase, Mitsuhiro Miyashita, Atsushi Imai, Akiko Kobori, Atsushi Nishida, Yasue Horiuchi, Masanari Itokawa, Kazuya Toriumi, Kazuhiro Niizato, and Heii Arai

Subjects
Oncology, Central Nervous System, Glycation End Products, Advanced, Male, Physiology, Receptor for Advanced Glycation End Products, Neuropsychological Tests, Biochemistry, Nervous System, Body Mass Index, chemistry.chemical_compound, 0302 clinical medicine, Cognition, Wisconsin Card Sorting Test, Glycation, Medicine and Health Sciences, Medicine, Antipsychotics, Post-Translational Modification, Cognitive Impairment, Liquid Chromatography, Multidisciplinary, Cognitive Neurology, Chromatographic Techniques, Neuropsychology, Wechsler Adult Intelligence Scale, Drugs, Middle Aged, Body Fluids, Blood, Neurology, Physiological Parameters, Schizophrenia, Advanced glycation end-product, Female, Anatomy, Research Article, medicine.medical_specialty, Science, Cognitive Neuroscience, Research and Analysis Methods, Arginine, Blood Plasma, 03 medical and health sciences, Internal medicine, Mental Health and Psychiatry, Humans, Cognitive Dysfunction, Pentosidine, Pharmacology, business.industry, Lysine, Body Weight, Biology and Life Sciences, Proteins, medicine.disease, High Performance Liquid Chromatography, 030227 psychiatry, Cross-Sectional Studies, chemistry, Cognitive Science, business, 030217 neurology & neurosurgery, Neuroscience
Abstract

Advanced glycation end products play a key role in the pathophysiology of schizophrenia. Cognitive impairment is one of the central features of schizophrenia; however, the association between advanced glycation end products and cognitive impairment remains unknown. This study investigated whether advanced glycation end products affect the cognitive domain in patients with schizophrenia. A total of 58 patients with chronic schizophrenia were included in this cross-sectional study. Plasma advanced glycation end products were measured using high-performance liquid chromatography (HPLC). Neuropsychological and cognitive functions were assessed using the Wechsler Adult Intelligence Scale, Third Version, and the Wisconsin Card Sorting Test Keio-FS version. Multiple regression analysis adjusted for age, sex, body mass index, educational years, daily dose of antipsychotics, and psychotic symptoms revealed that processing speed was significantly associated with plasma pentosidine, a representative advanced glycation end product (standardized β = -0.425; p = 0.009). Processing speed is the cognitive domain affected by advanced glycation end products. Considering preceding evidence that impaired processing speed is related to poor functional outcome, interventions targeted at reducing advanced glycation end products may contribute to promoting recovery of patients with schizophrenia as well as cognitive function improvement.

Published
2021

16. Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Author

Götz Thomalla, Florent Boutitie, Henry Ma, Masatoshi Koga, Peter Ringleb, Lee H Schwamm, Ona Wu, Martin Bendszus, Christopher F Bladin, Bruce C V Campbell, Bastian Cheng, Leonid Churilov, Martin Ebinger, Matthias Endres, Jochen B Fiebach, Mayumi Fukuda-Doi, Manabu Inoue, Timothy J Kleinig, Lawrence L Latour, Robin Lemmens, Christopher R Levi, Didier Leys, Kaori Miwa, Carlos A Molina, Keith W Muir, Norbert Nighoghossian, Mark W Parsons, Salvador Pedraza, Peter D Schellinger, Stefan Schwab, Claus Z Simonsen, Shlee S Song, Vincent Thijs, Danilo Toni, Chung Y Hsu, Nils Wahlgren, Haruko Yamamoto, Nawaf Yassi, Sohei Yoshimura, Steven Warach, Werner Hacke, Kazunori Toyoda, Geoffrey A Donnan, Stephen M Davis, Christian Gerloff, Boris Raul Acosta, Karen Aegidius, Christian Albiker, Anna Alegiani, Miriam Almendrote, Angelika Alonso, Katharina Althaus, Pierre Amarenco, Hemasse Amiri, Bettina Anders, Adriana Aniculaesei, Jason Appleton, Juan Arenillas, Christina Back, Christian Bähr, Jürgen Bardutzky, Flore Baronnet-Chauvet, Rouven Bathe-Peters, Anna Bayer-Karpinska, Juan L. Becerra, Christoph Beck, Olga Belchí Guillamon, Amandine Benoit, Nadia Berhoune, Daniela Bindila, Julia Birchenall, Karine Blanc-Lasserre, Miguel Blanco Gonzales, Tobias Bobinger, Ulf Bodechtel, Eric Bodiguel, Urszula Bojaryn, Louise Bonnet, Benjamin Bouamra, Paul Bourgeois, Lorenz Breuer, Ludovic Breynaert, David Broughton, Raf Brouns, Sébastian Brugirard, Bart Bruneel, Florian Buggle, Serkan Cakmak, Ana Calleja, David Calvet, David Carrera, Hsin-Chieh Chen, Bharath Cheripelli, Tae-Hee Cho, Chi-un Choe, Lillian Choy, Hanne Christensen, Mareva Ciatipis, Geoffrey Cloud, Julien Cogez, Elisa Cortijo, Sophie Crozier, Dorte Damgaard, Krishna Dani, Beatrijs De Coene, Isabel De Hollander, Jacques De Keyser, Nina De Klippel, Charlotte De Maeseneire, Ann De Smedt, Maria del Mar Castellanos Rodrigo, Sandrine Deltour, Jelle Demeestere, Laurent Derex, Philippe Desfontaines, Ralf Dittrich, Anand Dixit, Laurens Dobbels, Valérie Domigo, Laura Dorado, Charlotte Druart, Kristina Hougaard Dupont, Anne Dusart, Rainer Dziewas, Matthias Ebner, Myriam Edjali-Goujon, Philipp Eisele, Salwa El Tawil, Ahmed Elhfnawy, Ana Etexberria, Nicholas Evans, Simon Fandler, Franz Fazekas, Sandra Felix, Jochen B. Fiebach, Jens Fiehler, Alexandra Filipov, Katharina Filipski, Robert Fleischmann, Christian Foerch, Ian Ford, Alexandra Gaenslen, Ivana Galinovic, Elena Meseguer Gancedo, Ramanan Ganeshan, Carlos García Esperón, Alicia Garrido, Thomas Gattringer, Olivia Geraghty, Rohat Geran, Stefan Gerner, Sylvie Godon-Hardy, Jos Göhler, Amir Golsari, Meritxell Gomis, David Gorriz, Verena Gramse, Laia Grau, Martin Griebe, Cristina Guerrero, Damla Guerzoglu, Sophie Guettier, Vincent Guiraud, Christoph Gumbinger, Ignaz Gunreben, Florian Haertig, Christian Hametner, Bernard Hanseeuw, Andreas Hansen, Jakob Hansen, Thomas Harbo, Andreas Harloff, Peter Harmel, Karl Georg Häusler, Florian Heinen, Valentin Held, Simon Hellwig, Dimitri Hemelsoet, Michael Hennerici, Juliane Herm, Sylvia Hermans, María Hernández, Jose Hervas Vicente, Niels Hjort, Cristina Hobeanu, Carsten Hobohm, Elmar Höfner, Katharina Hohenbichler, Marc Hommel, Julia Hoppe, Eva Hornberger, Carolin Hoyer, Xuya Huang, Nils Ipsen, Irina Isern, Lourdes Ispierto, Helle Iversen, Lise Jeppesen, Marta Jimenez, Jan Jungehülsing, Eric Jüttler, Dheeraj Kalladka, Bernd Kallmünzer, Arindam Kar, Lars Kellert, André Kemmling, Tobias Kessler, Usman Khan, Matthias Klein, Christoph Kleinschnitz, Matti Klockziem, Michael Knops, Luzie Koehler, Martin Koehrmann, Heinz Kohlfürst, Rainer Kollmar, Peter Kraft, Thomas Krause, Bo Kristensen, Jan M. Kröber, Natalia Kurka, Alexandre Ladoux, Patrice Laloux, Catherine Lamy, Emmanuelle Landrault, Arne Lauer, Claire Lebely, Jonathan Leempoel, Kennedy Lees, Anne Leger, Laurence Legrand, Lin Li, Anna-Mareike Löbbe, Frederic London, Elena Lopez-cancio, Matthias Lorenz, Stephen Louw, Caroline Lovelock, Manuel Lozano Sánchez, Giuseppe Lucente, Janos Lückl, Alain Luna, Kosmas Macha, Alexandre Machet, Daniel Mackenrodt, Dominik Madzar, Charles Majoie, Anika Männer, Vicky Maqueda, Jacob Marstrand, Alicia Martinez, Annika Marzina, Laura Mechthouff, Per Meden, Guy Meersman, Julia Meier, Charles Mellerio, Oliver Menn, Nadja Meyer, Dominik Michalski, Peter Michels, Lene Michelsen, Monica Millán Torne, Jens Minnerup, Boris Modrau, Sebastian Moeller, Anette Møller, Nathalie Morel, Fiona Moreton, Ludovic Morin, Thierry Moulin, Barry Moynihan, Anne K. Mueller, Keith W. Muir, Patricia Mulero, Sibu Mundiyanapurath, Johannes Mutzenbach, Simon Nagel, Oliver Naggara, Arumugam Nallasivan, Irene Navalpotro, Alexander H. Nave, Paul Nederkoorn, Lars Neeb, Hermann Neugebauer, Tobias Neumann-Haefelin, Stefan Oberndorfer, Christian Opherk, Lorenz Oppel, Catherine Oppenheim, Johannes Orthgieß, Leif Ostergaard, Perrine Paindeville, Ernest Palomeras, Verena Panitz, Bhavni Patel, Andre Peeters, Dirk Peeters, Anna Pellisé, Johann Pelz, Anthony Pereira, Natalia Pérez de la Ossa, Richard Perry, Salvador Petraza, Stéphane Peysson, Waltraud Pfeilschifter, Alexander Pichler, Alexandra Pierskalla, Hans-Werner Pledl, Sven Poli, Katrin Pomrehn, Marika Poulsen, Luis Prats, Silvia Presas, Elisabeth Prohaska, Volker Puetz, Josep Puig, Josep Puig Alcántara, Jan Purrucker, Veronique Quenardelle, Sankaranarayanan Ramachandran, Soulliard Raphaelle, Nicolas Raposo, Tilman Reiff, Michel Remmers, Pauline Renou, Martin Ribitsch, Hardy Richter, Martin Ritter, Thomas Ritzenthaler, Gilles Rodier, Christine Rodriguez-Regent, Manuel Rodríguez-Yáñez, Maria Roennefarth, Christine Roffe, Sverre Rosenbaum, Charlotte Rosso, Joachim Röther, Michal Rozanski, Noelia Ruiz de Morales, Francesca Russo, Matthieu Rutgers, Sharmilla Sagnier, Yves Samson, Josep Sánchez, Tamara Sauer, Jan H. Schäfer, Simon Schieber, Josef Schill, Dennis Schlak, Ludwig Schlemm, Sein Schmidt, Wouter Schonewille, Julian Schröder, Andreas Schulz, Johannes Schurig, Sönke Schwarting, Alexander Schwarz, Christopher Schwarzbach, Matthias Seidel, Alexander Seiler, Jochen Sembill, Joaquin Serena Leal, Ashit Shetty, Igor Sibon, Claus Z. Simonsen, Oliver Singer, Aravinth Sivagnanaratham, Ide Smets, Craig Smith, Peter Soors, Nikola Sprigg, Maximilian Spruegel, David Stark, Susanne Steinert, Sebastian Stösser, Markus Stuermlinger, Bart Swinnen, Ruben Tamazyan, Jose Tembl, Mikel Terceno Izaga, Emmanuel Touze, Thomas Truelsen, Guillaume Turc, Gaetane Turine, Serdar Tütüncü, Pippa Tyrell, Xavier Ustrell, Wilfried Vadot, Anne-Evelyne Vallet, Pauline Vallet, Lucie van den Berg, Sophie van den Berg, Cecile van Eendenburg, Robbert-Jan Van Hooff, Isabelle van Sloten, Peter Vanacker, Evelien Vancaester, Patrick Vanderdonckt, Yves Vandermeeren, Frederik Vanhee, Roland Veltkamp, Karsten Vestergaard, Alain Viguier, Dolores Vilas, Kersten Villringer, Dieke Voget, Jörg von Schrader, Paul von Weitzel, Elisabeth Warburton, Claudia Weber, Jörg Weber, Karl Wegscheider, Mirko Wegscheider, Christian Weimar, Karin Weinstich, Christopher Weise, Gesa Weise, Chris Willems, Klemens Winder, Matthias Wittayer, Marc Wolf, Martin Wolf, Valerie Wolff, Christian Wollboldt, Frank Wollenweber, Anke Wouters, Bertrand Yalo, Marion Yger, Nadia Younan, Laetita Yperzeele, Vesna Zegarac, Pia Zeiner, Ulf Ziemann, Thomas Zonneveld, Mathieu Zuber, Tsugio Akutsu, Junya Aoki, Shuji Arakawa, Ryosuke Doijiri, Yusuke Egashira, Yukiko Enomoto, Eisuke Furui, Konosuke Furuta, Seiji Gotoh, Toshimitsu Hamasaki, Yasuhiro Hasegawa, Teryuki Hirano, Kazunari Homma, Masahiko Ichijyo, Toshihiro Ide, Shuichi Igarashi, Yasuyuki Iguchi, Masafumi Ihara, Hajime Ikenouchi, Tsuyoshi Inoue, Ryo Itabashi, Yasuhiro Ito, Toru Iwama, Kenji Kamiyama, Shoko Kamiyoshi, Haruka Kanai, Yasuhisa Kanematsu, Takao Kanzawa, Kazumi Kimura, Jiro Kitayama, Takanari Kitazono, Rei Kondo, Kohsuke Kudo, Masayoshi Kusumi, Ken Kuwahara, Shoji Matsumoto, Hideki Matsuoka, Ban Mihara, Kazuo Minematsu, Ken Miura, Naomi Morita, Wataru Mouri, Kayo Murata, Yoshinari Nagakane, Taizen Nakase, Hiromi Ohara, Nobuyuki Ohara, Hideyuki Ohnishi, Hajime Ohta, Masafumi Ohtaki, Ryo Ohtani, Toshiho Ohtsuki, Hideo Ohyama, Takashi Okada, Yasushi Okada, Masato Osaki, Nobuyuki Sakai, Yoshiki Sanbongi, Naoshi Sasaki, Makoto Sasaki, Shoichiro Sato, Kenta Seki, Wataru Shimizu, Yoshiaki Shiokawa, Takashi Sozu, Junichiro Suzuki, Rieko Suzuki, Yasushi Takagi, Shunya Takizawa, Norio Tanahashi, Eijiro Tanaka, Ryota Tanaka, Yohei Tateishi, Tomoaki Terada, Tadashi Terasaki, Kenichi Todo, Azusa Tokunaga, Akira Tsujino, Toshihiro Ueda, Yoshikazu Uesaka, Mihoko Uotani, Takao Urabe, Masao Watanabe, Yoshiki Yagita, Yusuke Yakushiji, Keizo Yasui, Toshiro Yonehara, Shinichi Yoshimura, K. Aarnio, F. Alemseged, C. Anderson, T. Ang, M.L. Archer, J. Attia, P. Bailey, A. Balabanski, A. Barber, P.A. Barber, J. Bernhardt, A. Bivard, D. Blacker, C.F. Bladin, A. Brodtmann, D. Cadilhac, B.C.V. Campbell, L. Carey, S. Celestino, L. Chan, W.H. Chang, A. ChangI, C.H. Chen, C.-I. Chen, H.F. Chen, T.C. Chen, W.H. Chen, Y.Y. Chen, C.A. Cheng, E. Cheong, Y.W. Chiou, P.M. Choi, H.J. Chu, C.S. Chuang, T.C. Chung, L. Churilov, B. Clissold, A. Connelly, S. Coote, B. Coulton, E. Cowley, J. Cranefield, S. Curtze, C. D'Este, S.M. Davis, S. Day, P.M. Desmond, H.M. Dewey, C. Ding, G.A. Donnan, R. Drew, S. Eirola, D. Field, T. Frost, C. Garcia-Esperon, K. George, R. Gerraty, R. Grimley, Y.C. Guo, G. Hankey, J. Harvey, S.C. Ho, K. Hogan, D. Howells, P.M. Hsiao, C.H. Hsu, C.T. Hsu, C.-S. Hsu, J.P. Hsu, Y.D. Hsu, Y.T. Hsu, C.J. Hu, C.C. Huang, H.Y. Huang, M.Y. Huang, S.C. Huang, W.S. Huang, D. Jackson, J.S. Jeng, S.K. Jiang, L. Kaauwai, O. Kasari, J. King, T.J. Kleinig, M. Koivu, J. Kolbe, M. Krause, C.W. Kuan, W.L. Kung, C. Kyndt, C.L. Lau, A. Lee, C.Y. Lee, J.T. Lee, Y. Lee, Y.C. Lee, C. Levi, C.R. Levi, L.M. Lien, J.C. Lim, C.C. Lin, C.H. Lin, C.M. Lin, D. Lin, C.H. Liu, J. Liu, Y.C. Lo, P.S. Loh, E. Low, C.H. Lu, C.J. Lu, M.K. Lu, J. Ly, H. Ma, L. Macaulay, R. Macdonnell, E. Mackey, M. Macleod, J. Mahadevan, V. Maxwell, R. McCoy, A. McDonald, S. McModie, A. Meretoja, S. Mishra, P.J. Mitchell, F. Miteff, A. Moore, C. Muller, F. Ng, F.C. Ng, J-L. Ng, W. O'Brian, V. O'Collins, T.J. Oxley, M.W. Parsons, S. Patel, G.S. Peng, L. Pesavento, T. Phan, E. Rodrigues, Z. Ross, A. Sabet, M. Sallaberger, P. Salvaris, D. Shah, G. Sharma, G. Sibolt, M. Simpson, S. Singhal, B. Snow, N. Spratt, R. Stark, J. Sturm, M.C. Sun, Y. Sun, P.S. Sung, Y.F. Sung, M. Suzuki, M. Tan, S.C. Tang, T. Tatlisumak, V. Thijs, M. Tiainen, C.H. Tsai, C.K. Tsai, C.L. Tsai, H.T. Tsai, L.K. Tsai, C.H. Tseng, L.T. Tseng, J. Tsoleridis, H. Tu, H.T-H. Tu, W. Vallat, J. Virta, W.C. Wang, Y.T. Wang, M. Waters, L. Weir, T. Wijeratne, C. Williams, W. Wilson, A.A. Wong, K. Wong, T.Y. Wu, Y.H. Wu, B. Yan, F.C. Yang, Y.W. Yang, N. Yassi, H.L. Yeh, J.H. Yeh, S.J. Yeh, C.H. Yen, D. Young, C.L. Ysai, W.W. Zhang, H. Zhao, L. Zhao, Katharina Althaus-Knaurer, Jörg Berrouschot, Erich Bluhmki, Paolo Bovi, Gilles Chatellier, Lynda Cove, Stephen Davis, A. Dixit, Geoffrey Donnan, Christina Ehrenkrona, Christoph Eschenfelder, Marc Fatar, Juan Francisco Arenillas, Franz Gruber, Lalit Kala, Peter Kapeller, Markku Kaste, Christof Kessler, Martin Köhrmann, Rico Laage, Kennedy R. Lees, Alain Luna Rodriguez, Jean-Louis Mas, Robert Mikulik, Carlos Molina, Girish Muddegowda, Keith Muir, Kurt Niederkorn, Xavier Nuñez, Peter Schellinger, Joaquin Serena, Jan Sobesky, Thorsten Steiner, Ann-Sofie Svenson, Rüdiger von Kummer, Joanna Wardlaw, Rebecca A. Betensky, Gregoire Boulouis, Raphael A. Carandang, William A. Copen, Pedro Cougo, Shawna Cutting, Kendra Drake, Andria L. Ford, John Hallenbeck, Gordon J. Harris, Robert Hoesch, Amie Hsia, Carlos Kase, Lawrence Latour, Michael H. Lev, Alona Muzikansky, Nandakumar Nagaraja, Lee H. Schwamm, Eric Searls, Shlee S. Song, Sidney Starkman, Albert J. Yoo, Ramin Zand, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Hospices Civils de Lyon (HCL), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Monash University [Melbourne], National Cerebral and Cardiovascular Center (NCCC - OSAKA), Osaka University [Osaka], University of Heidelberg, Medical Faculty, Massachusetts General Hospital [Boston], University of Melbourne, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Royal Adelaide Hospital [Adelaide Australia], National Institute of Neurological Disorders and Stroke [Bethesda] (NINDS), National Institutes of Health [Bethesda] (NIH), University Hospitals Leuven [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Flanders Make [Leuven], Flanders Make, University of Newcastle [Australia] (UoN), Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Vall d'Hebron University Hospital [Barcelona], University of Glasgow, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Girona Biomedical Research Institute [Girona, Spain] (IDIBGI), Ruhr-Universität Bochum [Bochum], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Aarhus University Hospital, Cedars-Sinai Medical Center, Florey Institute of Neuroscience and Mental Health [Melbourne, Victoria, Australia], Austin Health, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], China Medical University Hospital [Taichung], Karolinska Institutet [Stockholm], The Walter and Eliza Hall Institute of Medical Research (WEHI), University of Texas at Austin [Austin], Collaborators Evaluation of unknown Onset Stroke thrombolysis trials (EOS) investigators: Boris Raul Acosta, Karen Aegidius, Christian Albiker, Anna Alegiani, Miriam Almendrote, Angelika Alonso, Katharina Althaus, Pierre Amarenco, Hemasse Amiri, Bettina Anders, Adriana Aniculaesei, Jason Appleton, Juan Arenillas, Christina Back, Christian Bähr, Jürgen Bardutzky, Flore Baronnet-Chauvet, Rouven Bathe-Peters, Anna Bayer-Karpinska, Juan L Becerra, Christoph Beck, Olga Belchí Guillamon, Amandine Benoit, Nadia Berhoune, Daniela Bindila, Julia Birchenall, Karine Blanc-Lasserre, Miguel Blanco Gonzales, Tobias Bobinger, Ulf Bodechtel, Eric Bodiguel, Urszula Bojaryn, Louise Bonnet, Benjamin Bouamra, Paul Bourgeois, Florent Boutitie, Lorenz Breuer, Ludovic Breynaert, David Broughton, Raf Brouns, Sébastian Brugirard, Bart Bruneel, Florian Buggle, Serkan Cakmak, Ana Calleja, David Calvet, David Carrera, Hsin-Chieh Chen, Bastian Cheng, Bharath Cheripelli, Tae-Hee Cho, Chi-Un Choe, Lillian Choy, Hanne Christensen, Mareva Ciatipis, Geoffrey Cloud, Julien Cogez, Elisa Cortijo, Sophie Crozier, Dorte Damgaard, Krishna Dani, Beatrijs De Coene, Isabel De Hollander, Jacques De Keyser, Nina De Klippel, Charlotte De Maeseneire, Ann De Smedt, Maria Del Mar Castellanos Rodrigo, Sandrine Deltour, Jelle Demeestere, Laurent Derex, Philippe Desfontaines, Ralf Dittrich, Anand Dixit, Laurens Dobbels, Valérie Domigo, Laura Dorado, Charlotte Druart, Kristina Hougaard Dupont, Anne Dusart, Rainer Dziewas, Martin Ebinger, Matthias Ebner, Myriam Edjali-Goujon, Philipp Eisele, Salwa El Tawil, Ahmed Elhfnawy, Matthias Endres, Ana Etexberria, Nicholas Evans, Simon Fandler, Franz Fazekas, Sandra Felix, Jochen B Fiebach, Jens Fiehler, Alexandra Filipov, Katharina Filipski, Robert Fleischmann, Christian Foerch, Ian Ford, Alexandra Gaenslen, Ivana Galinovic, Elena Meseguer Gancedo, Ramanan Ganeshan, Carlos García Esperón, Alicia Garrido, Thomas Gattringer, Olivia Geraghty, Rohat Geran, Christian Gerloff, Stefan Gerner, Sylvie Godon-Hardy, Jos Göhler, Amir Golsari, Meritxell Gomis, David Gorriz, Verena Gramse, Laia Grau, Martin Griebe, Cristina Guerrero, Damla Guerzoglu, Sophie Guettier, Vincent Guiraud, Christoph Gumbinger, Ignaz Gunreben, Florian Haertig, Christian Hametner, Bernard Hanseeuw, Andreas Hansen, Jakob Hansen, Thomas Harbo, Andreas Harloff, Peter Harmel, Karl Georg Häusler, Florian Heinen, Valentin Held, Simon Hellwig, Dimitri Hemelsoet, Michael Hennerici, Juliane Herm, Sylvia Hermans, María Hernández, Jose Hervas Vicente, Niels Hjort, Cristina Hobeanu, Carsten Hobohm, Elmar Höfner, Katharina Hohenbichler, Marc Hommel, Julia Hoppe, Eva Hornberger, Carolin Hoyer, Xuya Huang, Nils Ipsen, Irina Isern, Lourdes Ispierto, Helle Iversen, Lise Jeppesen, Marta Jimenez, Jan Jungehülsing, Eric Jüttler, Dheeraj Kalladka, Bernd Kallmünzer, Arindam Kar, Lars Kellert, André Kemmling, Tobias Kessler, Usman Khan, Matthias Klein, Christoph Kleinschnitz, Matti Klockziem, Michael Knops, Luzie Koehler, Martin Koehrmann, Heinz Kohlfürst, Rainer Kollmar, Peter Kraft, Thomas Krause, Bo Kristensen, Jan M Kröber, Natalia Kurka, Alexandre Ladoux, Patrice Laloux, Catherine Lamy, Emmanuelle Landrault, Arne Lauer, Claire Lebely, Jonathan Leempoel, Kennedy Lees, Anne Leger, Laurence Legrand, Robin Lemmens, Lin Li, Anna-Mareike Löbbe, Frederic London, Elena Lopez-Cancio, Matthias Lorenz, Stephen Louw, Caroline Lovelock, Manuel Lozano Sánchez, Giuseppe Lucente, Janos Lückl, Alain Luna, Kosmas Macha, Alexandre Machet, Daniel Mackenrodt, Dominik Madzar, Charles Majoie, Anika Männer, Vicky Maqueda, Jacob Marstrand, Alicia Martinez, Annika Marzina, Laura Mechthouff, Per Meden, Guy Meersman, Julia Meier, Charles Mellerio, Oliver Menn, Nadja Meyer, Dominik Michalski, Peter Michels, Lene Michelsen, Monica Millán Torne, Jens Minnerup, Boris Modrau, Sebastian Moeller, Anette Møller, Nathalie Morel, Fiona Moreton, Ludovic Morin, Thierry Moulin, Barry Moynihan, Anne K Mueller, Keith W Muir, Patricia Mulero, Sibu Mundiyanapurath, Johannes Mutzenbach, Simon Nagel, Oliver Naggara, Arumugam Nallasivan, Irene Navalpotro, Alexander H Nave, Paul Nederkoorn, Lars Neeb, Hermann Neugebauer, Tobias Neumann-Haefelin, Norbert Nighoghossian, Stefan Oberndorfer, Christian Opherk, Lorenz Oppel, Catherine Oppenheim, Johannes Orthgieß, Leif Ostergaard, Perrine Paindeville, Ernest Palomeras, Verena Panitz, Bhavni Patel, Andre Peeters, Dirk Peeters, Anna Pellisé, Johann Pelz, Anthony Pereira, Natalia Pérez de la Ossa, Richard Perry, Salvador Petraza, Stéphane Peysson, Waltraud Pfeilschifter, Alexander Pichler, Alexandra Pierskalla, Hans-Werner Pledl, Sven Poli, Katrin Pomrehn, Marika Poulsen, Luis Prats, Silvia Presas, Elisabeth Prohaska, Volker Puetz, Josep Puig, Josep Puig Alcántara, Jan Purrucker, Veronique Quenardelle, Sankaranarayanan Ramachandran, Soulliard Raphaelle, Nicolas Raposo, Tilman Reiff, Michel Remmers, Pauline Renou, Martin Ribitsch, Hardy Richter, Peter Ringleb, Martin Ritter, Thomas Ritzenthaler, Gilles Rodier, Christine Rodriguez-Regent, Manuel Rodríguez-Yáñez, Maria Roennefarth, Christine Roffe, Sverre Rosenbaum, Charlotte Rosso, Joachim Röther, Michal Rozanski, Noelia Ruiz de Morales, Francesca Russo, Matthieu Rutgers, Sharmilla Sagnier, Yves Samson, Josep Sánchez, Tamara Sauer, Jan H Schäfer, Simon Schieber, Josef Schill, Dennis Schlak, Ludwig Schlemm, Sein Schmidt, Wouter Schonewille, Julian Schröder, Andreas Schulz, Johannes Schurig, Sönke Schwarting, Alexander Schwarz, Christopher Schwarzbach, Matthias Seidel, Alexander Seiler, Jochen Sembill, Joaquin Serena Leal, Ashit Shetty, Igor Sibon, Claus Z Simonsen, Oliver Singer, Aravinth Sivagnanaratham, Ide Smets, Craig Smith, Peter Soors, Nikola Sprigg, Maximilian Spruegel, David Stark, Susanne Steinert, Sebastian Stösser, Markus Stuermlinger, Bart Swinnen, Ruben Tamazyan, Jose Tembl, Mikel Terceno Izaga, Vincent Thijs, Götz Thomalla, Emmanuel Touze, Thomas Truelsen, Guillaume Turc, Gaetane Turine, Serdar Tütüncü, Pippa Tyrell, Xavier Ustrell, Wilfried Vadot, Anne-Evelyne Vallet, Pauline Vallet, Lucie van den Berg, Sophie van den Berg, Cecile van Eendenburg, Robbert-Jan Van Hooff, Isabelle van Sloten, Peter Vanacker, Evelien Vancaester, Patrick Vanderdonckt, Yves Vandermeeren, Frederik Vanhee, Roland Veltkamp, Karsten Vestergaard, Alain Viguier, Dolores Vilas, Kersten Villringer, Dieke Voget, Jörg von Schrader, Paul von Weitzel, Elisabeth Warburton, Claudia Weber, Jörg Weber, Karl Wegscheider, Mirko Wegscheider, Christian Weimar, Karin Weinstich, Christopher Weise, Gesa Weise, Chris Willems, Klemens Winder, Matthias Wittayer, Marc Wolf, Martin Wolf, Valerie Wolff, Christian Wollboldt, Frank Wollenweber, Anke Wouters, Bertrand Yalo, Marion Yger, Nadia Younan, Laetita Yperzeele, Vesna Zegarac, Pia Zeiner, Ulf Ziemann, Thomas Zonneveld, Mathieu Zuber, Tsugio Akutsu, Junya Aoki, Junya Aoki, Shuji Arakawa, Ryosuke Doijiri, Yusuke Egashira, Yukiko Enomoto, Mayumi Fukuda-Doi, Eisuke Furui, Konosuke Furuta, Seiji Gotoh, Toshimitsu Hamasaki, Yasuhiro Hasegawa, Teryuki Hirano, Kazunari Homma, Masahiko Ichijyo, Toshihiro Ide, Shuichi Igarashi, Yasuyuki Iguchi, Masafumi Ihara, Hajime Ikenouchi, Manabu Inoue, Tsuyoshi Inoue, Ryo Itabashi, Yasuhiro Ito, Toru Iwama, Kenji Kamiyama, Shoko Kamiyoshi, Haruka Kanai, Yasuhisa Kanematsu, Takao Kanzawa, Kazumi Kimura, Jiro Kitayama, Takanari Kitazono, Masatoshi Koga, Rei Kondo, Kohsuke Kudo, Masayoshi Kusumi, Ken Kuwahara, Shoji Matsumoto, Hideki Matsuoka, Ban Mihara, Kazuo Minematsu, Ken Miura, Kaori Miwa, Naomi Morita, Wataru Mouri, Kayo Murata, Yoshinari Nagakane, Taizen Nakase, Hiromi Ohara, Nobuyuki Ohara, Hideyuki Ohnishi, Hajime Ohta, Masafumi Ohtaki, Ryo Ohtani, Toshiho Ohtsuki, Hideo Ohyama, Takashi Okada, Yasushi Okada, Masato Osaki, Nobuyuki Sakai, Yoshiki Sanbongi, Naoshi Sasaki, Makoto Sasaki, Shoichiro Sato, Kenta Seki, Wataru Shimizu, Yoshiaki Shiokawa, Takashi Sozu, Junichiro Suzuki, Rieko Suzuki, Yasushi Takagi, Shunya Takizawa, Norio Tanahashi, Eijiro Tanaka, Ryota Tanaka, Yohei Tateishi, Tomoaki Terada, Tadashi Terasaki, Kenichi Todo, Azusa Tokunaga, Kazunori Toyoda, Akira Tsujino, Toshihiro Ueda, Yoshikazu Uesaka, Mihoko Uotani, Takao Urabe, Masao Watanabe, Yoshiki Yagita, Yusuke Yakushiji, Haruko Yamamoto, Keizo Yasui, Toshiro Yonehara, Sohei Yoshimura, Shinichi Yoshimura, K Aarnio, F Alemseged, C Anderson, T Ang, M L Archer, J Attia, P Bailey, A Balabanski, A Barber, P A Barber, J Bernhardt, A Bivard, D Blacker, C F Bladin, A Brodtmann, D Cadilhac, B C V Campbell, L Carey, S Celestino, L Chan, W H Chang, A ChangI, C H Chen, C-I Chen, H F Chen, T C Chen, W H Chen, Y Y Chen, C A Cheng, E Cheong, Y W Chiou, P M Choi, H J Chu, C S Chuang, T C Chung, L Churilov, B Clissold, A Connelly, S Coote, B Coulton, E Cowley, J Cranefield, S Curtze, C D'Este, S M Davis, S Day, P M Desmond, H M Dewey, C Ding, G A Donnan, R Drew, S Eirola, D Field, T Frost, C Garcia-Esperon, K George, R Gerraty, R Grimley, Y C Guo, G Hankey, J Harvey, S C Ho, K Hogan, D Howells, P M Hsiao, C H Hsu, C T Hsu, C-S Hsu, J P Hsu, Y D Hsu, Y T Hsu, C J Hu, C C Huang, H Y Huang, M Y Huang, S C Huang, W S Huang, D Jackson, J S Jeng, S K Jiang, L Kaauwai, O Kasari, J King, T J Kleinig, M Koivu, J Kolbe, M Krause, C W Kuan, W L Kung, C Kyndt, C L Lau, A Lee, C Y Lee, J T Lee, Y Lee, Y C Lee, C Levi, C R Levi, L M Lien, J C Lim, C C Lin, C H Lin, C M Lin, D Lin, C H Liu, J Liu, Y C Lo, P S Loh, E Low, C H Lu, C J Lu, M K Lu, J Ly, H Ma, L Macaulay, R Macdonnell, E Mackey, M Macleod, J Mahadevan, V Maxwell, R McCoy, A McDonald, S McModie, A Meretoja, S Mishra, P J Mitchell, F Miteff, A Moore, C Muller, F Ng, F C Ng, J-L Ng, W O'Brian, V O'Collins, T J Oxley, M W Parsons, S Patel, G S Peng, L Pesavento, T Phan, E Rodrigues, Z Ross, A Sabet, M Sallaberger, P Salvaris, D Shah, G Sharma, G Sibolt, M Simpson, S Singhal, B Snow, N Spratt, R Stark, J Sturm, M C Sun, Y Sun, P S Sung, Y F Sung, M Suzuki, M Tan, S C Tang, T Tatlisumak, V Thijs, M Tiainen, C H Tsai, C K Tsai, C L Tsai, H T Tsai, L K Tsai, C H Tseng, L T Tseng, J Tsoleridis, H Tu, H T-H Tu, W Vallat, J Virta, W C Wang, Y T Wang, M Waters, L Weir, T Wijeratne, C Williams, W Wilson, A A Wong, K Wong, T Y Wu, Y H Wu, B Yan, F C Yang, Y W Yang, N Yassi, H L Yeh, J H Yeh, S J Yeh, C H Yen, D Young, C L Ysai, W W Zhang, H Zhao, L Zhao, Katharina Althaus-Knaurer, Martin Bendszus, Jörg Berrouschot, Erich Bluhmki, Paolo Bovi, Gilles Chatellier, Lynda Cove, Stephen Davis, A Dixit, Geoffrey Donnan, Rainer Dziewas, Christina Ehrenkrona, Christoph Eschenfelder, Marc Fatar, Juan Francisco Arenillas, Franz Gruber, Werner Hacke, Lalit Kala, Peter Kapeller, Markku Kaste, Christof Kessler, Martin Köhrmann, Rico Laage, Kennedy R Lees, Didier Leys, Alain Luna Rodriguez, Jean-Louis Mas, Robert Mikulik, Carlos Molina, Girish Muddegowda, Keith Muir, Kurt Niederkorn, Xavier Nuñez, Catherine Oppenheim, Sven Poli, Peter Ringleb, Peter Schellinger, Stefan Schwab, Joaquin Serena, Jan Sobesky, Thorsten Steiner, Ann-Sofie Svenson, Danilo Toni, Roland Veltkamp, Rüdiger von Kummer, Nils Wahlgren, Joanna Wardlaw, Rebecca A Betensky, Gregoire Boulouis, Raphael A Carandang, William A Copen, Pedro Cougo, Shawna Cutting, Kendra Drake, Andria L Ford, John Hallenbeck, Gordon J Harris, Robert Hoesch, Amie Hsia, Carlos Kase, Lawrence Latour, Arne Lauer, Michael H Lev, Alona Muzikansky, Nandakumar Nagaraja, Lee H Schwamm, Eric Searls, Shlee S Song, Sidney Starkman, Steven Warach, Ona Wu, Albert J Yoo, Ramin Zand, University of Newcastle [Callaghan, Australia] (UoN), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CarMeN, laboratoire, Yperzeele, Laetitia, Evaluation of Unknown Onset Stroke Thrombolysis trials (EOS) investigators, UCL - SSS/IONS - Institute of NeuroScience, UCL - (MGD) Service de neurologie, Supporting clinical sciences, UZB Other, Physical Medicine and Rehabilitation, Clinical sciences, Neuroprotection & Neuromodulation, Radiology and Nuclear Medicine, ANS - Neurovascular Disorders, Neurology, ACS - Atherosclerosis & ischemic syndromes, Graduate School, Center of Experimental and Molecular Medicine, ACS - Pulmonary hypertension & thrombosis, and ACS - Microcirculation

Subjects
medicine.medical_treatment, [SDV]Life Sciences [q-bio], Ischemic Stroke/*diagnostic imaging/*drug therapy, Tomography, X-Ray Computed/methods, Fibrinolytic Agents/adverse effects/*therapeutic use, 030204 cardiovascular system & hematology, Ischemic Stroke/diagnostic imaging, surgery, 0302 clinical medicine, Modified Rankin Scale, 030212 general & internal medicine, 10. No inequality, Infusions, Intravenous, Stroke, Tomography, Time-to-Treatment, General Medicine, Thrombolysis, X-Ray Computed/methods, Tissue Plasminogen Activator/adverse effects, 3. Good health, [SDV] Life Sciences [q-bio], Diffusion Magnetic Resonance Imaging/methods, Treatment Outcome, Meta-analysis, Tissue Plasminogen Activator, Intravenous, medicine.medical_specialty, Infusions, Intravenous thrombolysis, Neuroimaging, Neuroscience(all), Placebo, Tissue Plasminogen Activator/adverse effects/*therapeutic use, 03 medical and health sciences, Fibrinolytic Agents, Internal medicine, medicine, Humans, ddc:610, Ischemic Stroke, business.industry, neurology, Fibrinolytic Agents/adverse effects, Odds ratio, Recovery of Function, medicine.disease, Clinical research, Diffusion Magnetic Resonance Imaging, Human medicine, business, Tomography, X-Ray Computed, Fibrinolytic agent
Abstract

International audience; BACKGROUND: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. METHODS: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. FINDINGS: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I(2)=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [\textless1%], adjusted OR 5·58 [1·22-25·50]; p=0·024). INTERPRETATION: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. FUNDING: None.

Published
2020
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17. A case of recurrent Mikulicz’s disease with mononeuritis multiplex

Author

Eiichiro Nagata, Maiko Kouchi, Shunya Takizawa, Sachiko Yutani, Tsuyoshi Uesugi, Chikage Kijima, and Atsushi Mizuma

Subjects
medicine.medical_specialty, Weakness, Immunology, lcsh:Medicine, Case Report, Neurological examination, Mikulicz's disease, mononeuritis multiplex, 03 medical and health sciences, 0302 clinical medicine, Immunology and Allergy, Medicine, 030212 general & internal medicine, steroid therapy, 030203 arthritis & rheumatology, Mikulicz’s disease, IgG4, medicine.diagnostic_test, Salivary gland, Mononeuritis Multiplex, business.industry, Maintenance dose, lcsh:R, Deep Tendon Reflex, Surgery, Steroid therapy, medicine.anatomical_structure, medicine.symptom, business
Abstract

We report an 82-year-old man with recurrence of Mikulicz’s disease accompanied with mononeuritis multiplex. On admission, both upper eyelids, the salivary gland, the dorsum of the left hand and both legs were swollen. Neurological examination showed motor weakness of distal limbs (manual muscle testing 3/5) and decreased touch, pain and vibration sensation of the dorsum of the left hand and both legs. Deep tendon reflex in both legs was also decreased. We diagnosed Mikulicz’s disease based on high serum immunoglobulin (Ig)G4 (630 mg/dl, 26.1% of total IgG) and lacrimal gland biopsy findings. Clinical symptoms and motor conduction study findings improved after steroid therapy. However, tapering of the steroid dose resulted in recurrence two years later. Steroid therapy is usually effective for IgG4-related neuropathy, and we found that an increase of steroid dose was effective to treat the recurrence. But, in general, a suitable maintenance dose of steroid in combination with an immunosuppressant may be necessary to prevent relapse.

Published
2018

18. Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome) Complicated by Perforation of the Small Intestine and Cholecystitis

Author

Yoichi Ohnuki, Taira Nakayama, Shunya Takizawa, Sachiko Yutani, Naoya Nakamura, Chie Inomoto, Yusuke Moriya, Soichiro Yamamoto, Yuko Ohnuki, Shuji Uda, and Atsushi Mizuma

Subjects
Male, medicine.medical_specialty, Prednisolone, Perforation (oil well), Churg-Strauss syndrome, Case Report, Gastroenterology, Hypesthesia, 03 medical and health sciences, Necrosis, 0302 clinical medicine, Maintenance therapy, cholecystitis, Adrenal Cortex Hormones, Internal medicine, hemic and lymphatic diseases, Eosinophilic, Intestine, Small, Internal Medicine, Medicine, Eosinophilia, Humans, perforation of small intestine, Aged, 030203 arthritis & rheumatology, Muscle Weakness, business.industry, Mononeuritis Multiplex, Mononeuropathies, Granulomatosis with Polyangiitis, Immunoglobulins, Intravenous, General Medicine, medicine.disease, Asthma, eosinophilic granulomatosis with polyangiitis, Intestinal Perforation, Cholecystitis, 030211 gastroenterology & hepatology, medicine.symptom, business, Complication, Granulomatosis with polyangiitis, Immunosuppressive Agents
Abstract

We report a case of eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss syndrome) complicated by perforation of the small intestine and necrotizing cholecystitis. A 69-year-old man with a history of bronchial asthma was admitted with mononeuritis multiplex. The laboratory findings included remarkable eosinophilia. He was treated with corticosteroids and his laboratory indices showed improvement; however, his functional deficits remained. His neuropathy gradually improved after the addition of intravenous immunoglobulin (IVIG). He was subsequently treated with oral prednisolone (40 mg/day) as maintenance therapy. Within a month after finishing IVIG, he developed perforation of the small intestine and necrotizing cholecystitis. Intestinal perforation has often been reported as a gastrointestinal complication of EGPA. In contrast, cholecystitis is a rare complication. We report this case because the manifestation of more than one complication is extremely rare. Gastrointestinal symptoms may be a complication of EGPA itself and/or immunosuppressive treatment.

Published
2017

19. On-Ground Calibration of the Hitomi Hard X-ray Telescopes

Author

Naoki Ishida, Satoshi Sugita, Sasagu Tachibana, Kenji Tachibana, Housei Nagano, Keiji Ogi, Daichi Kurihara, Yuzuru Tawara, Toshihiro Iwase, Shunya Takizawa, Naotsugu Shima, Kentaro Uesugi, Yasushi Ogasaka, Masayuki Itoh, Tadatsugu Demoto, Yuuji Kuroda, Toshiki Sato, Yoshifumi Meshino, Y. Miyata, Yoshito Haba, Ayako Bandai, Ryo Iizuka, Hideyuki Mori, Ikuyuki Mitsuishi, Keisuke Tamura, Yoshio Suzuki, Hironori Matsumoto, Hiroaki Kobayashi, Tatsuro Kosaka, Manabu Ishida, Takayuki Hayashi, Shigetaka Saji, Takashi Okajima, Takuya Miyazawa, Yoshiharu Namba, Kazuki Tomikawa, Akihiro Furuzawa, Fumiya Shimasaki, Takuro Sato, Hiroyoshi Kato, Shou Kurashima, Hideyo Kunieda, Yoshitomo Maeda, Hisamitsu Awaki, Yasunori Babazaki, Koujun Yamashita, Kazunori Ishibashi, Shigeo Yamauchi, and Tatsuharu Torii

Subjects
Physics::Instrumentation and Detectors, Astrophysics::High Energy Astrophysical Phenomena, X-ray telescope, Field of view, 01 natural sciences, 010309 optics, Optics, Hitomi (ASTRO-H), 0103 physical sciences, Angular resolution, 010303 astronomy & astrophysics, Instrumentation, Image resolution, x-ray mirrors, Physics, Vignetting, business.industry, Mechanical Engineering, Antenna aperture, Astronomy and Astrophysics, multilayer mirrors, Electronic, Optical and Magnetic Materials, astronomical optics, Beamline, Space and Planetary Science, Control and Systems Engineering, Reflection (physics), business
Abstract

著者人数: 49名, Accepted: 2017-12-18, 資料番号: SA1170329000

Published
2018

20. A novel inhibitor of plasminogen activator inhibitor-1 provides antithrombotic benefits devoid of bleeding effect in nonhuman primates

Author

Nagahisa Yamaoka, Takashi Dan, Kanji Meguro, Hidehiko Kodama, Shunya Takizawa, Noriaki Hirayama, Charles van Ypersele de Strihou, Yuko Izuhara, Toshio Miyata, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, and UCL - (SLuc) Service de néphrologie

Subjects
Models, Molecular, Male, Protein Conformation, Piperazines, Rats, Sprague-Dawley, chemistry.chemical_compound, Mice, Antithrombotic, para-Aminobenzoates, tissue plasminogen activator, medicine.diagnostic_test, Molecular Structure, PAI-1 inhibitor, Clopidogrel, Neurology, Tissue Plasminogen Activator, Plasminogen activator inhibitor-1, Original Article, Female, Cardiology and Cardiovascular Medicine, 4-Aminobenzoic Acid, Partial thromboplastin time, medicine.drug, medicine.medical_specialty, Ticlopidine, Serine Proteinase Inhibitors, Hemorrhage, Structure-Activity Relationship, Fibrinolytic Agents, Bleeding time, Internal medicine, Plasminogen Activator Inhibitor 1, medicine, Humans, Animals, Platelet activation, Rats, Wistar, thrombosis, business.industry, T-plasminogen activator, Thrombosis, bleeding, Rats, Macaca fascicularis, Disease Models, Animal, Endocrinology, chemistry, Drug Design, cynomolgus monkey, Neurology (clinical), business, Plasminogen activator
Abstract

Inhibition of plasminogen activator inhibitor (PAI)-1 is useful to treat several disorders including thrombosis. An inhibitor of PAI-1 (TM5275) was newly identified by an extensive study of structure-activity relationship based on a lead compound (TM5007) which was obtained through virtual screening by docking simulations. Its antithrombotic efficacy and adverse effects were tested in vivo in rats and nonhuman primates (cynomolgus monkey). TM5275, administered orally in rats (1 to 10 mg/kg), has an antithrombotic effect equivalent to that of ticlopidine (500 mg/kg) in an arterialvenous shunt thrombosis model and to that of clopidogrel (3 mg/kg) in a ferric chloride-treated carotid artery thrombosis model. TM5275 does not modify activated partial thromboplastin time and prothrombin time or platelet activity and does not prolong bleeding time. Combined with tissue plasminogen activator, TM5275 improves the latter's therapeutic efficacy and reduces its adverse effect. Administered to a monkey model of photochemical induced arterial thrombosis, TM5275 (10 mg/kg) has the same antithrombotic effect as clopidogrel (10 mg/kg), without enhanced bleeding. This study documents the antithrombotic benefits of a novel, more powerful, PAI-1 inhibitor in rats and, for the first time, in nonhuman primates. These effects are obtained without adverse effect on bleeding time. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 904-912; doi: 10.1038/jcbfm.2009.272; published online 20 January 2010

Published
2010

21. Higher Risk of Ischemic Events in Secondary Prevention for Patients With Persistent Than Those With Paroxysmal Atrial Fibrillation.

Author

Masatoshi Koga, Sohei Yoshimura, Yasuhiro Hasegawa, Satoshi Shibuya, Yasuhiro Ito, Hideki Matsuoka, Kazuhiro Takamatsu, Kazutoshi Nishiyama, Kenichi Todo, Kazumi Kimura, Eisuke Furui, Tadashi Terasaki, Yoshiaki Shiokawa, Kenji Kamiyama, Shunya Takizawa, Satoshi Okuda, Yasushi Okada, Tomoaki Kameda, Yoshinari Nagakane, and Yoshiki Yagita

Published
2016
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24. Cobalt ameliorates renal injury in an obese, hypertensive type 2 diabetes rat model.

Author

Shuichi Ohtomo, Masaomi Nangaku, Yuko Izuhara, Shunya Takizawa, Charles van Ypersele de Strihou, and Toshio Miyata

Subjects
TYPE 2 diabetes, GROWTH factors, CEREBRAL anoxia, KIDNEY diseases
Abstract

Background. Chronic renal hypoxia is suspected to play a pathogenic role in the genesis of diabetic nephropathy (DN). Cobalt enhances the activity of the hypoxia-inducible factor (HIF), a key factor in the defence against hypoxia. Its long-term effect on DN is evaluated. Methods. Cobalt chloride was given to hypertensive, type 2 diabetic rats with nephropathy (SHR/NDmcr-cp). Treatment was initiated at the age of 13 weeks and continued for 26 weeks. Results. Cobalt did not correct hypertension and metabolic abnormalities (obesity, hyperglycaemia and hyperlipidaemia) but reduced proteinuria as well as histological kidney injury. Cobalt upregulated renal HIF-1alpha and HIF-2alpha expression and increased the expression of HIF-regulated genes, including erythropoietin, vascular endothelial growth factor and heme oxygenase-1. The renal expression of transforming growth factor (TGF)-beta and connective tissue growth factor (CTGF) was significantly reduced by cobalt. The renal expression of NADPH oxidase, a marker of oxidative stress, and the renal content of pentosidine, a marker of advanced glycation, were also significantly reduced by cobalt. Conclusions. Cobalt achieved renal protection independently of metabolic status and blood pressure. Its effect was attributed to the upregulation of HIF and HIF-regulated genes and to a mitigated advanced glycation and oxidative stress. [ABSTRACT FROM AUTHOR]

Published
2008

25. A novel class of advanced glycation inhibitors ameliorates renal and cardiovascular damage in experimental rat models.

Author

Yuko Izuhara, Masaomi Nangaku, Shunya Takizawa, Satoru Takahashi, Jing Shao, Hisashi Oishi, Hiroyuki Kobayashi, Charles van Ypersele de Strihou, and Toshio Miyata

Subjects
ANGIOTENSINS, TYROSINE, BLOOD pressure, ISCHEMIA
Abstract

Background. The reno- and cardiovascular-protective effects of angiotensin II receptor blockers (ARBs), have been ascribed, at least in part, to their ability to inhibit the formation of advanced glycation end products (AGEs), independently of their effect on blood pressure. They act through decreased oxidative stress, unlike previously reported AGE inhibitors which entrap reactive carbonyl (RCOs) precursors of AGEs. The hypotensive effects of ARBs’, however, may limit their use. In the present study, we report the synthesis of a new AGE inhibitor, TM2002, and its effects in vitro and in vivo. Methods. We screened a large chemical library (∼1300 compounds) including edaravone, a drug used to treat cerebral infarction, for in vitro AGE inhibitory activity. Based upon the structure-function analysis of edaravone derivatives, we synthesized a novel AGE inhibitor, 1-(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)-6-methyl-1,3-dihydro-furo[3,4-c]pyridine-7-ol (TM2002). We delineate in vitro the biological characteristics of TM22002, evaluate in vivo its toxico-pharmacokinetics and document in animal models of rat, their renal and cardiovascular protective effectiveness. Results. Screening of a large chemical library disclosed that edaravone inhibits in vitro AGE formation efficiently. Unfortunately, like most AGE inhibitors, it also traps pyridoxal, limiting its clinical usefulness. We therefore synthesized a novel AGE inhibitor, TM2002, that does not trap pyridoxal. In vitro, TM2002 shows powerful AGE inhibitory activity. Markers of oxidation, i.e. o-tyrosine formation and transition metal chelation, are efficiently inhibited by TM2002-like ARBs. TM2002 does not bind to the angiotensin II type 1 receptor. It is readily bioavailable and non-toxic. In vivo, TM2002, given acutely or for 8 weeks, has no adverse effects. In four different rat models of renal injury (anti-Thy1 and ischaemia-reperfusion) and cardiovascular injury (carotid artery balloon injury and angiotensin II-induced cardiac fibrosis), TM2002 improves renal and cardiovascular lesions without modification of blood pressure. Conclusions. TM2002 is a novel, non-toxic AGE inhibitor acting through ARB-like mechanisms, able to prevent renal and cardiovascular diseases independently of blood pressure lowering. [ABSTRACT FROM AUTHOR]

Published
2008

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