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Article: [Stem Cell Therapy for Neurological Diseases].

Niizuma, Kuniyasu

Brain and nerve = Shinkei kenkyu no shinpo

2023 Volume 75, Issue 2, Page(s) 167–172

Abstract: Recently, regenerative medicine, a field of medicine which focuses on the repair or replacement of damaged or lost tissues, has been of great interest. Although stem cell therapies for neurological diseases are still controversial, recent studies ... ...

Abstract	Recently, regenerative medicine, a field of medicine which focuses on the repair or replacement of damaged or lost tissues, has been of great interest. Although stem cell therapies for neurological diseases are still controversial, recent studies demonstrated positive treatment effects. In this review, stem cell therapy mechanisms are described focusing on recent findings. Moreover, clinical trial results are also summarized.
MeSH term(s)	Humans ; Regenerative Medicine/methods ; Nervous System Diseases ; Stem Cell Transplantation/methods
Language	Japanese
Publishing date	2023-02-07
Publishing country	Japan
Document type	Review ; English Abstract ; Journal Article
ZDB-ID	390389-8
ISSN	1344-8129 ; 1881-6096 ; 0006-8969
ISSN (online)	1344-8129
ISSN	1881-6096 ; 0006-8969
DOI	10.11477/mf.1416202299
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Article ; Online: Endovascular Treatment of Wide-Neck Bifurcation Aneurysm: Recent Trends in Coil Embolization with Adjunctive Technique.

Haryu, Shinya / Sakata, Hiroyuki / Matsumoto, Yasushi / Niizuma, Kuniyasu / Endo, Hidenori

Journal of neuroendovascular therapy

2024 Volume 18, Issue 3, Page(s) 75–83

Abstract: Wide-neck bifurcation aneurysms (WNBAs) are sometimes challenging to treat. During endovascular treatment, it is important to prevent coil deviation and preserve normal vessels. Adjunctive balloon- and stent-assisted techniques have been developed. A ... ...

Abstract	Wide-neck bifurcation aneurysms (WNBAs) are sometimes challenging to treat. During endovascular treatment, it is important to prevent coil deviation and preserve normal vessels. Adjunctive balloon- and stent-assisted techniques have been developed. A meta-analysis of endovascular treatments of WNBAs revealed that only 40% of patients had complete occlusion. Recently, novel devices have been developed to expand the range of treatment options. Flow-diverter stents and intra-aneurysmal flow disruption devices do not require coils; however, coil embolization remains the standard procedure used by many neurointerventionists. This review describes the recent trends in adjunctive techniques for supporting coil embolization for WNBAs. We referred to literature on balloon-assisted techniques, stent-assisted techniques, Y-stenting, PulseRider, Barrel stents, Comaneci temporary stents, pCONUS, and eCLIPs. These reports showed that adequate embolization rates were generally greater than 80%, and the complete occlusion rate was as high as 94.6%. All devices had a relatively high occlusion rate; however, it may be inaccurate to simply compare each device because of the heterogeneity of the studies. It is important to select the best treatment for each individual case by considering not only literature-based efficacy and safety but also patient background, aneurysm characteristics, and operator experience.
Language	English
Publishing date	2024-01-13
Publishing country	Japan
Document type	Journal Article ; Review
ISSN	2186-2494
ISSN (online)	2186-2494
DOI	10.5797/jnet.ra.2023-0072
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Article ; Online: Cerebral venous sinus thrombosis detected using diffusion-weighted magnetic resonance imaging during maintenance temozolomide chemotherapy in a patient with glioblastoma: illustrative case.

Takeuchi, Youhei / Saito, Ryuta / Kanamori, Masayuki / Niizuma, Kuniyasu / Mugikura, Shunji / Endo, Hidenori

Journal of neurosurgery. Case lessons

2024 Volume 7, Issue 9

Abstract: Background: Cerebral venous sinus thrombosis (CVST) sometimes occurs in the background of hypercoagulopathic disorders, including malignancy, chemotherapy, etc. Glioblastoma (GBM) is a malignancy found in the central nervous system, and reports on cases ...

Abstract	Background: Cerebral venous sinus thrombosis (CVST) sometimes occurs in the background of hypercoagulopathic disorders, including malignancy, chemotherapy, etc. Glioblastoma (GBM) is a malignancy found in the central nervous system, and reports on cases of GBM complicated by CVST are sparse. The authors herein report a case of GBM complicated by CVST during maintenance temozolomide (TMZ) chemotherapy and describe the utility of diffusion-weighted magnetic resonance imaging (MRI) for the detection of CVST. Observations: A 65-year-old male was treated for left temporal GBM. After surgical removal of the lesion, the patient was treated with chemoradiation therapy, which included 60 Gy local radiation with concomitant TMZ chemotherapy. He was subsequently received TMZ maintenance therapy. Routine MRI performed 7 months after surgery revealed no evidence of tumor recurrence. However, diffusion-weighted imaging (DWI) revealed a high-intensity signal at the posterior portion of the superior sagittal sinus, indicating the presence of a thrombus. In addition to the preexisting symptoms, the patient experienced some disorientation. Angiography revealed an obstruction in the superior sagittal sinus, right transverse sinus, right sigmoid sinus, and straight sinus. His symptoms improved with endovascular and anticoagulant therapy. Lessons: Performing DWI during routine follow-up can help in the early diagnosis of CVST in patients with malignant gliomas.
Language	English
Publishing date	2024-02-26
Publishing country	United States
Document type	Journal Article
ISSN	2694-1902
ISSN (online)	2694-1902
DOI	10.3171/CASE23762
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Article ; Online: Donor Muse Cell Treatment Without HLA-Matching Tests and Immunosuppressant Treatment.

Minatoguchi, Shinya / Fujita, Yasuyuki / Niizuma, Kuniyasu / Tominaga, Teiji / Yamashita, Toru / Abe, Koji / Dezawa, Mari

Stem cells translational medicine

2024

Abstract: The strength of stem cell therapy is the regeneration of tissues by synergistic pleiotropic effects. Among many stem cell types, mesenchymal stem cells (MSCs) that are comprised of heterogenous population are widely used for clinical applications with ... ...

Abstract	The strength of stem cell therapy is the regeneration of tissues by synergistic pleiotropic effects. Among many stem cell types, mesenchymal stem cells (MSCs) that are comprised of heterogenous population are widely used for clinical applications with the expectation of pleiotropic bystander effects. Muse cells are pluripotent-like/macrophage-like stem cells distributed in the bone marrow, peripheral blood, and organ connective tissues as cells positive for the pluripotent surface marker stage-specific-embryonic antigen -3. Muse cells comprise ~1% to several percent of MSCs. While Muse cells and MSCs share several characteristics, such as mesenchymal surface marker expression and their bystander effects, Muse cells exhibit unique characteristics not observed in MSCs. These unique characteristics of Muse cells include selective homing to damaged tissue after intravenous injection rather than being trapped in the lung like MSCs, replacement of a wide range of damaged/apoptotic cells by differentiation through phagocytosis, and long-lasting immunotolerance for donor cell use. In this review, we focus on the basic properties of Muse cells clarified through preclinical studies and clinical trials conducted by intravenous injection of donor-Muse cells without HLA-matching tests or immunosuppressant treatment. MSCs are considered to differentiate into osteogenic, chondrogenic, and adipogenic cells, whereas the range of their differentiation has long been debated. Muse cells may provide clues to the wide-ranging differentiation potential of MSCs that are observed with low frequency. Furthermore, the utilization of Muse cells may provide a novel strategy for clinical treatment.
Language	English
Publishing date	2024-04-01
Publishing country	England
Document type	Journal Article
ZDB-ID	2642270-0
ISSN	2157-6580 ; 2157-6580
ISSN (online)	2157-6580
ISSN	2157-6580
DOI	10.1093/stcltm/szae018
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Article ; Online: Distinguishing IDH mutation status in gliomas using FTIR-ATR spectra of peripheral blood plasma indicating clear traces of protein amyloid aggregation.

Kino, Saiko / Kanamori, Masayuki / Shimoda, Yoshiteru / Niizuma, Kuniyasu / Endo, Hidenori / Matsuura, Yuji

BMC cancer

2024 Volume 24, Issue 1, Page(s) 222

Abstract: Background: Glioma is a primary brain tumor and the assessment of its molecular profile in a minimally invasive manner is important in determining treatment strategies. Among the molecular abnormalities of gliomas, mutations in the isocitrate ... ...

Abstract	Background: Glioma is a primary brain tumor and the assessment of its molecular profile in a minimally invasive manner is important in determining treatment strategies. Among the molecular abnormalities of gliomas, mutations in the isocitrate dehydrogenase (IDH) gene are strong predictors of treatment sensitivity and prognosis. In this study, we attempted to non-invasively diagnose glioma development and the presence of IDH mutations using multivariate analysis of the plasma mid-infrared absorption spectra for a comprehensive and sensitive view of changes in blood components associated with the disease and genetic mutations. These component changes are discussed in terms of absorption wavenumbers that contribute to differentiation. Methods: Plasma samples were collected at our institutes from 84 patients with glioma (13 oligodendrogliomas, 17 IDH-mutant astrocytoma, 7 IDH wild-type diffuse glioma, and 47 glioblastomas) before treatment initiation and 72 healthy participants. FTIR-ATR spectra were obtained for each plasma sample, and PLS discriminant analysis was performed using the absorbance of each wavenumber in the fingerprint region of biomolecules as the explanatory variable. This data was used to distinguish patients with glioma from healthy participants and diagnose the presence of IDH mutations. Results: The derived classification algorithm distinguished the patients with glioma from healthy participants with 83% accuracy (area under the curve (AUC) in receiver operating characteristic (ROC) = 0.908) and diagnosed the presence of IDH mutation with 75% accuracy (AUC = 0.752 in ROC) in cross-validation using 30% of the total test data. The characteristic changes in the absorption spectra suggest an increase in the ratio of β-sheet structures in the conformational composition of blood proteins of patients with glioma. Furthermore, these changes were more pronounced in patients with IDH-mutant gliomas. Conclusions: The plasma infrared absorption spectra could be used to diagnose gliomas and the presence of IDH mutations in gliomas with a high degree of accuracy. The spectral shape of the protein absorption band showed that the ratio of β-sheet structures in blood proteins was significantly higher in patients with glioma than in healthy participants, and protein aggregation was a distinct feature in patients with glioma with IDH mutations.
MeSH term(s)	Humans ; Ataxia Telangiectasia Mutated Proteins/genetics ; Blood Proteins/metabolism ; Brain Neoplasms/diagnosis ; Brain Neoplasms/genetics ; Brain Neoplasms/pathology ; Glioma/diagnosis ; Glioma/genetics ; Glioma/metabolism ; Isocitrate Dehydrogenase/genetics ; Isocitrate Dehydrogenase/metabolism ; Mutation ; Protein Aggregates ; Spectroscopy, Fourier Transform Infrared ; Amyloid/metabolism
Chemical Substances	Ataxia Telangiectasia Mutated Proteins (EC 2.7.11.1) ; ATR protein, human (EC 2.7.11.1) ; Blood Proteins ; Isocitrate Dehydrogenase (EC 1.1.1.41) ; Protein Aggregates ; Amyloid
Language	English
Publishing date	2024-02-16
Publishing country	England
Document type	Journal Article
ZDB-ID	2041352-X
ISSN	1471-2407 ; 1471-2407
ISSN (online)	1471-2407
ISSN	1471-2407
DOI	10.1186/s12885-024-11970-y
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Article ; Online: Intravenous Administration of Human Muse Cells Ameliorates Deficits in a Rat Model of Subacute Spinal Cord Injury.

Takahashi, Yoshiharu / Kajitani, Takumi / Endo, Toshiki / Nakayashiki, Atsushi / Inoue, Tomoo / Niizuma, Kuniyasu / Tominaga, Teiji

International journal of molecular sciences

2023 Volume 24, Issue 19

Abstract: Multilineage-differentiating stress-enduring (Muse) cells are newly established pluripotent stem cells. The aim of the present study was to examine the potential of the systemic administration of Muse cells as an effective treatment for subacute SCI. We ... ...

Abstract	Multilineage-differentiating stress-enduring (Muse) cells are newly established pluripotent stem cells. The aim of the present study was to examine the potential of the systemic administration of Muse cells as an effective treatment for subacute SCI. We intravenously administered the clinical product "CL2020" containing Muse cells to a rat model two weeks after mid-thoracic spinal cord contusion. Eight experimental animals received CL2020, and twelve received the vehicle. Behavioral analyses were conducted over 20 weeks. Histological evaluations were performed. After 20 weeks of observation, diphtheria toxin was administered to three CL2020-treated animals to selectively ablate human cell functions. Hindlimb motor functions significantly improved from 6 to 20 weeks after the administration of CL2020. The cystic cavity was smaller in the CL2020 group. Furthermore, larger numbers of descending 5-HT fibers were preserved in the distal spinal cord. Muse cells in CL2020 were considered to have differentiated into neuronal and neural cells in the injured spinal cord. Neuronal and neural cells were identified in the gray and white matter, respectively. Importantly, these effects were reversed by the selective ablation of human cells by diphtheria toxin. Intravenously administered Muse cells facilitated the therapeutic potential of CL2020 for severe subacute spinal cord injury.
MeSH term(s)	Rats ; Humans ; Animals ; Alprostadil ; Diphtheria Toxin ; Spinal Cord Injuries/therapy ; Cell Differentiation/physiology ; Spinal Cord ; Administration, Intravenous
Chemical Substances	Alprostadil (F5TD010360) ; Diphtheria Toxin
Language	English
Publishing date	2023-09-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241914603
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Article ; Online: Usefulness of the Double-Lumen Super-Compliant Balloon Catheter "Super-Masamune" for Balloon-Assisted Coil Embolization of Carotid-Cavernous Fistulas.

Morita, Takahiro / Niizuma, Kuniyasu / Endo, Hidenori / Tominaga, Teiji

Journal of neuroendovascular therapy

2021 Volume 15, Issue 9, Page(s) 615–620

Abstract: Objective: Transarterial embolization (TAE) of the cavernous sinus (CS) via a fistula formed in the internal carotid artery (ICA) is the standard for carotid-cavernous fistulas (CCFs). Depending on the fistula, an adjunctive technique using a balloon or ...

Abstract	Objective: Transarterial embolization (TAE) of the cavernous sinus (CS) via a fistula formed in the internal carotid artery (ICA) is the standard for carotid-cavernous fistulas (CCFs). Depending on the fistula, an adjunctive technique using a balloon or stent is effective. We report a case in which the balloon-assisted technique using the super-compliant balloon catheter "Super-Masamune" was effective. Case presentation: A 44-year-old woman who sustained head trauma from a traffic accident 1 month prior presented with diplopia, conjunctival chemosis, and proptosis of the left eye. Digital subtraction angiography (DSA) revealed a left CCF with a reflex to the left superior ophthalmic vein (SOV). During TAE with the Super-Masamune assistance, we tightly embolized around the fistula using a small volume of coils and the CCF was obliterated. Conclusion: The balloon of the Super-Masamune is made of a styrene-based elastomer, which has excellent compliance. Therefore, it is possible to reduce the volume of coils because the balloon is in close contact with the ICA or fistula. This may reduce the incidence of postoperative cranial nerve palsy and cost of treatment materials.
Language	English
Publishing date	2021-01-20
Publishing country	Japan
Document type	Case Reports
ISSN	2186-2494
ISSN (online)	2186-2494
DOI	10.5797/jnet.cr.2020-0110
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Article ; Online: RNF213 loss of function reshapes vascular transcriptome and spliceosome leading to disrupted angiogenesis and aggravated vascular inflammatory responses.

Zhang, Liyin / Rashad, Sherif / Zhou, Yuan / Niizuma, Kuniyasu / Tominaga, Teiji

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

2022 Volume 42, Issue 11, Page(s) 2107–2122

Abstract: RNF213 gene mutations are the cause behind Moyamoya disease, a rare cerebrovascular occlusive disease. However, the function of RNF213 in the vascular system and the impact of its loss of function are not yet comprehended. To understand RNF23 function, ... ...

Abstract	RNF213 gene mutations are the cause behind Moyamoya disease, a rare cerebrovascular occlusive disease. However, the function of RNF213 in the vascular system and the impact of its loss of function are not yet comprehended. To understand RNF23 function, we performed gene knockdown (KD) in vascular cells and performed various phenotypical analysis as well as extensive transcriptome and epitranscriptome profiling. Our data revealed that RNF213 KD led to disrupted angiogenesis in HUVEC, in part due to downregulation of DNA replication and proliferation pathways. Furthermore, HUVEC cells became sensitive to LPS induced inflammation after RNF213 KD, leading to retarded cell migration and enhanced macrophage transmigration. This was evident at the level of transcriptome as well. Interestingly, RNF213 led to extensive changes in mRNA splicing that were not previously reported. In vascular smooth muscle cells (vSMCs), RNF213 KD led to alteration in cytoskeletal organization, contractility, and vSMCs function related pathways. Finally, RNF213 KD disrupted endothelial-to-vSMCs communication in co-culture models. Overall, our results indicate that RNF213 KD sensitizes endothelial cells to inflammation, leading to altered angiogenesis. Our results shed the light on the important links between RNF213 mutations and inflammatory/immune inducers of MMD and on the unexplored role of epitranscriptome in MMD.
MeSH term(s)	Adenosine Triphosphatases/genetics ; Human Umbilical Vein Endothelial Cells/metabolism ; Humans ; Inflammation/genetics ; Lipopolysaccharides ; Moyamoya Disease ; Neovascularization, Pathologic/genetics ; RNA, Messenger ; Spliceosomes/metabolism ; Transcription Factors ; Transcriptome ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism
Chemical Substances	Lipopolysaccharides ; RNA, Messenger ; Transcription Factors ; RNF213 protein, human (EC 2.3.2.27) ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Adenosine Triphosphatases (EC 3.6.1.-)
Language	English
Publishing date	2022-06-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604628-9
ISSN	1559-7016 ; 0271-678X
ISSN (online)	1559-7016
ISSN	0271-678X
DOI	10.1177/0271678X221110679
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Article: Erratum to "Carotid computed tomography angiography after cobalt-based alloy carotid artery stenting using ultra-high-resolution computed tomography with model-based iterative reconstruction" [Radiol Case Rep 2021;16:3721-8].

Kayano, Shingo / Ota, Hideki / Sato, Yoshimichi / Endo, Toshiki / Niizuma, Kuniyasu / Suzuki, Ichiro / Kawamura, Tsuyoshi / Takase, Kei

Radiology case reports

2023 Volume 18, Issue 6, Page(s) 2324

Abstract: This corrects the article DOI: 10.1016/j.radcr.2021.09.003.]. ...

Abstract	[This corrects the article DOI: 10.1016/j.radcr.2021.09.003.].
Language	English
Publishing date	2023-03-31
Publishing country	Netherlands
Document type	Published Erratum
ZDB-ID	2406300-9
ISSN	1930-0433
ISSN	1930-0433
DOI	10.1016/j.radcr.2023.03.021
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Article ; Online: Intravenous Administration of Human Muse Cells Ameliorates Deficits in a Rat Model of Subacute Spinal Cord Injury

Yoshiharu Takahashi / Takumi Kajitani / Toshiki Endo / Atsushi Nakayashiki / Tomoo Inoue / Kuniyasu Niizuma / Teiji Tominaga

International Journal of Molecular Sciences, Vol 24, Iss 14603, p

2023 Volume 14603

Abstract	Multilineage-differentiating stress-enduring (Muse) cells are newly established pluripotent stem cells. The aim of the present study was to examine the potential of the systemic administration of Muse cells as an effective treatment for subacute SCI. We intravenously administered the clinical product “CL2020” containing Muse cells to a rat model two weeks after mid-thoracic spinal cord contusion. Eight experimental animals received CL2020, and twelve received the vehicle. Behavioral analyses were conducted over 20 weeks. Histological evaluations were performed. After 20 weeks of observation, diphtheria toxin was administered to three CL2020-treated animals to selectively ablate human cell functions. Hindlimb motor functions significantly improved from 6 to 20 weeks after the administration of CL2020. The cystic cavity was smaller in the CL2020 group. Furthermore, larger numbers of descending 5-HT fibers were preserved in the distal spinal cord. Muse cells in CL2020 were considered to have differentiated into neuronal and neural cells in the injured spinal cord. Neuronal and neural cells were identified in the gray and white matter, respectively. Importantly, these effects were reversed by the selective ablation of human cells by diphtheria toxin. Intravenously administered Muse cells facilitated the therapeutic potential of CL2020 for severe subacute spinal cord injury.
Keywords	muse cell ; intravenous administration ; rat ; spinal cord injury ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2023-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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