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Article ; Online: Oxygen-dependent regulation of immune checkpoint mechanisms.

Ohta, Akio

2018 Volume 30, Issue 8, Page(s) 335–343

Abstract: Immunotherapy of cancer has finally materialized following the success of immune checkpoint blockade. Since down-regulation of immune checkpoint mechanisms is beneficial in cancer treatment, it is important to ask why tumors are infamously filled with ... ...

Abstract	Immunotherapy of cancer has finally materialized following the success of immune checkpoint blockade. Since down-regulation of immune checkpoint mechanisms is beneficial in cancer treatment, it is important to ask why tumors are infamously filled with the immunosuppressive mechanisms. Indeed, immune checkpoints are physiological negative feedback mechanisms of immune activities, and the induction of such mechanisms is important in preventing excessive destruction of inflamed normal tissues. A condition commonly found in tumors and inflamed tissues is tissue hypoxia. Oxygen deprivation under hypoxic conditions by itself is immunosuppressive because proper oxygen supply could support bioenergetic demands of immune cells for optimal immune responses. However, importantly, hypoxia has been found to up-regulate a variety of immune checkpoints and to be able to drive a shift toward a more immunosuppressive environment. Moreover, extracellular adenosine, which accumulates due to tissue hypoxia, also contributes to the up-regulation of other immune checkpoints. Taken together, tissue oxygen is a key regulator of the immune response by directly affecting the energy status of immune effectors and by regulating the intensity of immunoregulatory activity in the environment. The regulators of various immune checkpoint mechanisms may represent the next focus to modulate the intensity of immune responses and to improve cancer immunotherapy.
MeSH term(s)	Animals ; Humans ; Immunotherapy ; Neoplasms/immunology ; Neoplasms/pathology ; Neoplasms/therapy ; Oxygen/metabolism
Chemical Substances	Oxygen (S88TT14065)
Language	English
Publishing date	2018-05-30
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1013745-2
ISSN	1460-2377 ; 0953-8178
ISSN (online)	1460-2377
ISSN	0953-8178
DOI	10.1093/intimm/dxy038
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Article ; Online: No Impact of Contact Between the Medial Collar of a Hydroxyapatite-Coated Triple-Tapered Stem and the Femoral Neck on Periprosthetic Bone Mineral Density.

Iwakiri, Kentaro / Ohta, Yoichi / Minoda, Yukihide / Ueno, Shuhei / Kobayashi, Akio / Nakamura, Hiroaki

The Journal of arthroplasty

2024

Abstract: Background: Hydroxyapatite-coated, triple-tapered, shorter-length stems with a medial collar have been reported with good results for a few years. We investigated whether contact between the medial collar and femoral neck affects clinical outcomes and ... ...

Abstract	Background: Hydroxyapatite-coated, triple-tapered, shorter-length stems with a medial collar have been reported with good results for a few years. We investigated whether contact between the medial collar and femoral neck affects clinical outcomes and changes in bone mineral density (BMD) in patients who have this type of stem in their total hip arthroplasty construct. Methods: This was a retrospective, single-center study involving 62 patients scheduled for unilateral total hip arthroplasty using a hydroxyapatite-coated, triple-tapered, shorter-length stem who were followed for at least 1 year postoperatively. All patients had a Dorr type B femoral canal shape. Contact between the medial collar and the femoral neck was evaluated by computed tomography at the third postoperative month, and patients were classified into 2 groups. Postoperative clinical outcomes were investigated by the Western Ontario and McMaster Universities Arthritis Index and the Japanese Orthopaedic Association scores; radiological evaluation included stem fixation, spot welds and cortical hypertrophy, postoperative 3-dimensional stem alignment, and periprosthetic BMD changes. Results: There were 51 patients in the Contact + group (collar and neck contact) and 11 in the Contact-group (no contact). There were no differences between the 2 groups in the improvement of Western Ontario and McMaster Universities Arthritis Index and Japanese Orthopaedic Association scores, stem fixation, occurrence of cortical hypertrophy, or 3-dimensional stem alignment. Radiolucent lines were present in zones 3, 4, and 5 in 6 patients (12%) in the Contact + group only, who had no statistical difference between the 2 groups. Bone mineral density (BMD) decreased most in zone 7 in both groups, with no difference between the 2 groups. Conclusions: The presence or absence of contact between the medial collar and femoral neck did not affect postoperative BMD changes or radiological or clinical results. Level of evidence: Therapeutic Level III.
Language	English
Publishing date	2024-02-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	632770-9
ISSN	1532-8406 ; 0883-5403
ISSN (online)	1532-8406
ISSN	0883-5403
DOI	10.1016/j.arth.2024.02.011
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Article: A Metabolic Immune Checkpoint: Adenosine in Tumor Microenvironment.

Ohta, Akio

Frontiers in immunology

2016 Volume 7, Page(s) 109

Abstract: Within tumors, some areas are less oxygenated than others. Since their home ground is under chronic hypoxia, tumor cells adapt to this condition by activating aerobic glycolysis; however, this hypoxic environment is very harsh for incoming immune cells. ... ...

Abstract	Within tumors, some areas are less oxygenated than others. Since their home ground is under chronic hypoxia, tumor cells adapt to this condition by activating aerobic glycolysis; however, this hypoxic environment is very harsh for incoming immune cells. Deprivation of oxygen limits availability of energy sources and induces accumulation of extracellular adenosine in tumors. Extracellular adenosine, upon binding with adenosine receptors on the surface of various immune cells, suppresses pro-inflammatory activities. In addition, signaling through adenosine receptors upregulates a number of anti-inflammatory molecules and immunoregulatory cells, leading to the establishment of a long-lasting immunosuppressive environment. Thus, due to hypoxia and adenosine, tumors can discourage antitumor immune responses no matter how the response was induced, whether it was spontaneous or artificially introduced with a therapeutic intention. Preclinical studies have shown the significance of adenosine in tumor survival strategy by demonstrating tumor regression after inactivation of adenosine receptors, inhibition of adenosine-producing enzymes, or reversal of tissue hypoxia. These promising results indicate a potential use of the inhibitors of the hypoxia-adenosine pathway for cancer immunotherapy.
Language	English
Publishing date	2016
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2016.00109
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Article: Measurement of spinopelvic sagittal alignment in the relaxed seated position rather than in the straight seated position is suitable for assessing spinopelvic mobility in patients before total hip arthroplasty.

Ohyama, Yohei / Iwakiri, Kentaro / Ohta, Yoichi / Minoda, Yukihide / Kobayashi, Akio / Nakamura, Hiroaki

SICOT-J

2023 Volume 9, Page(s) 2

Abstract: Purpose: The relationship between spinopelvic mobility and dislocation in total hip arthroplasty (THA) has recently attracted attention. This study aimed to investigate the differences in sacral slope (SS) between two types of upright seated positions ... ...

Abstract	Purpose: The relationship between spinopelvic mobility and dislocation in total hip arthroplasty (THA) has recently attracted attention. This study aimed to investigate the differences in sacral slope (SS) between two types of upright seated positions and to determine which seated position was appropriate for assessing spinopelvic mobility (change in SS from standing to sitting) before THA. Materials and methods: This prospective cohort study included 75 hips from 75 patients who had undergone primary THA. Each patient underwent preoperative lateral spinopelvic radiography in standing (st) and two seated positions: relaxed (rs) and straight (ss). The change in SS between each position (Δ) was measured. Results: Differences in all spinopelvic sagittal alignment parameters between the two seated positions were statistically significant (p < 0.001). The range, median, and mean values of ΔSS Conclusion: The change in SS from the straight to the relaxed seated position widely varied in patients before THA. The spinopelvic radiograph in the relaxed seated position is appropriate when evaluating spinopelvic mobility for preoperative planning.
Language	English
Publishing date	2023-01-17
Publishing country	France
Document type	Journal Article
ZDB-ID	2832091-8
ISSN	2426-8887
ISSN	2426-8887
DOI	10.1051/sicotj/2022051
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Article ; Online: Calf extra-Fascial compartment area affects calf muscle pumping action: an air plethysmography and computed tomography study.

Mitsuoka, Hiroki / Ohta, Takashi / Arima, Takahiro / Sugimoto, Ikuo / Orimoto, Yuki / Kodama, Akio / Ishibashi, Hiroyuki

Phlebology

2023 Volume 38, Issue 5, Page(s) 334–340

Abstract: Objectives: We aimed to elucidate whether lower limb extra-fascial compartment and muscle areas affect the calf muscle pumping action on lower limbs.: Method: This study included 90 patients (180 limbs) who underwent preoperative air plethysmography ( ...

Abstract	Objectives: We aimed to elucidate whether lower limb extra-fascial compartment and muscle areas affect the calf muscle pumping action on lower limbs. Method: This study included 90 patients (180 limbs) who underwent preoperative air plethysmography (APG) and preoperative non-contrast computed tomography (CT) of the lower limbs for diagnosis of unilateral or bilateral primary varicose veins. A correlation between cross-sectional CT images and preoperative APG was confirmed. Cross-sectional CT was used to measure the extra-fascial compartment and muscle areas of the calf. The lower limbs were divided into two groups: those that were normal and those with primary varicose veins. Results: The extra-fascial compartment area was significantly correlated with the ejection fraction in normal (r = 0.388, Conclusions: In normal and varicose limbs, evaluation of ejection fraction, an indicator of muscle pumping, requires consideration of the extra-fascial compartment area.
MeSH term(s)	Humans ; Venous Insufficiency/diagnosis ; Leg/diagnostic imaging ; Leg/blood supply ; Varicose Veins/diagnosis ; Plethysmography ; Muscle, Skeletal/diagnostic imaging ; Tomography
Language	English
Publishing date	2023-05-03
Publishing country	England
Document type	Journal Article
ZDB-ID	645172-x
ISSN	1758-1125 ; 0268-3555
ISSN (online)	1758-1125
ISSN	0268-3555
DOI	10.1177/02683555231173747
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Zs.A 2538: Show issues

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Article ; Online: Stem alignment with short tapered-wedge cementless stems affects bone mineral density continuously for at least 5 years after primary total hip arthroplasty.

Masuda, Sho / Iwakiri, Kentaro / Ohta, Yoichi / Minoda, Yukihide / Kobayashi, Akio / Nakamura, Hiroaki

Hip international : the journal of clinical and experimental research on hip pathology and therapy

2023 Volume 34, Issue 1, Page(s) 57–65

Abstract: Aim: This study aimed to assess the relationship between the three-dimensional (3D) alignment of short tapered-wedge cementless stems and bone mineral density (BMD) changes in patients followed up for 5 years after total hip arthroplasty (THA).: ... ...

Abstract	Aim: This study aimed to assess the relationship between the three-dimensional (3D) alignment of short tapered-wedge cementless stems and bone mineral density (BMD) changes in patients followed up for 5 years after total hip arthroplasty (THA). Methods: We retrospectively analysed the hips of 52 patients who underwent THA using short tapered-wedge cementless stems at our institution from 2013 to 2016 with complete 5-year follow-up data. We evaluated the relationship between stem alignment, measured using a 3D-templating software, and BMD changes in the 7 Gruen zones. Results: After 1 year, significant negative correlations between varus insertion and a decrease in BMD in zone 7 and between flexed insertion and decreases in BMD in zones 3 and 4 were noted. After 5 years, significant negative correlations between varus insertion and a decrease in BMD in zone 7 and between flexed insertion and decreases in BMD zones 2, 3, and 4 were observed. With increased amounts of varus/flexion stem alignment, the amount of BMD loss decreased. There was no correlation between anteverted stem insertion and changes in BMD levels. Conclusions: Our data showed that stem alignment affects BMD based on 5-year follow-up data after surgery. Careful observation is necessary, especially when using short tapered-wedge cementless stems, as stem alignment may affect changes in BMD levels more than 5 years after surgery.
MeSH term(s)	Humans ; Arthroplasty, Replacement, Hip/adverse effects ; Arthroplasty, Replacement, Hip/methods ; Bone Density ; Hip Prosthesis ; Retrospective Studies ; Prosthesis Design ; Femur/surgery
Language	English
Publishing date	2023-06-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	1162513-2
ISSN	1724-6067 ; 1120-7000
ISSN (online)	1724-6067
ISSN	1120-7000
DOI	10.1177/11207000231178984
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Article ; Online: STAT5 interferes with PD-1 transcriptional activation and affects CD8+ T-cell sensitivity to PD-1-dependent immunoregulation.

Wang, Guanning / Tajima, Masaki / Honjo, Tasuku / Ohta, Akio

International immunology

2021 Volume 33, Issue 11, Page(s) 563–572

Abstract: Programmed cell death-1 (PD-1) is a co-inhibitory receptor that dampens immune responses upon interaction with PD-L1 and PD-L2. Although PD-1 expression on T cells is known to be activation-dependent, how cytokines modify its regulation is not fully ... ...

Abstract	Programmed cell death-1 (PD-1) is a co-inhibitory receptor that dampens immune responses upon interaction with PD-L1 and PD-L2. Although PD-1 expression on T cells is known to be activation-dependent, how cytokines modify its regulation is not fully resolved. Using polyclonal T-cell activation to study cytokine-dependent PD-1 regulation, we found that IL-2 inhibited transcriptional up-regulation of PD-1 despite the promotion of T-cell activation. The IL-2-mediated reduction in PD-1 expression augmented CD8+ T-cell activities against PD-L1-expressing target cells. To study the mechanism of PD-1 reduction, we focused on STAT5 activation in the IL-2 signaling pathway. Bioinformatic analysis suggested a novel conserved PD-1 promoter domain where NFAT and STAT5 can potentially compete with each other for binding. NFAT1 interaction with this domain revealed substantial potency in PD-1 transcription compared to STAT5A, and STAT5A overexpression could quench NFAT1-dependent PD-1 up-regulation in a sequence-specific manner. Chromatin immunoprecipitation analysis of activated T cells showed that IL-2 treatment significantly diminished the binding of NFAT1 and NFAT2 in the hypothesized competition site, while STAT5 binding to the same region was increased. These results raise the possibility that the competition of transcriptional factors might be involved in the fine-tuning of PD-1 expression by cytokines such as IL-2.
MeSH term(s)	Animals ; CD8-Positive T-Lymphocytes/immunology ; Cells, Cultured ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Programmed Cell Death 1 Receptor/deficiency ; Programmed Cell Death 1 Receptor/genetics ; Programmed Cell Death 1 Receptor/immunology ; STAT5 Transcription Factor/immunology
Chemical Substances	Pdcd1 protein, mouse ; Programmed Cell Death 1 Receptor ; STAT5 Transcription Factor ; Stat5a protein, mouse
Language	English
Publishing date	2021-09-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1013745-2
ISSN	1460-2377 ; 0953-8178
ISSN (online)	1460-2377
ISSN	0953-8178
DOI	10.1093/intimm/dxab059
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Article ; Online: A Case of Anti-IgLON5 Disease Showing an Improvement in Dysautonomia, Including Vocal Cord Palsy, via Combined Immunotherapy.

Sato, Daisuke / Sato, Hiroyasu / Kondo, Toshiyuki / Igari, Ryosuke / Iseki, Chifumi / Kawahara, Hikaru / Amano, Shintaro / Ono, Yoya / Kimura, Akio / Shimohata, Takayoshi / Ohta, Yasuyuki

Internal medicine (Tokyo, Japan)

2024

Abstract: Anti-IgLON5 disease shows various neurological manifestations, of which dysautonomia is one of the major symptoms and is rarely improved by immunotherapy. We herein report a patient with anti-IgLON5 disease who showed several autonomic failures, ... ...

Abstract	Anti-IgLON5 disease shows various neurological manifestations, of which dysautonomia is one of the major symptoms and is rarely improved by immunotherapy. We herein report a patient with anti-IgLON5 disease who showed several autonomic failures, including vocal cord palsy for four months. The patient presented with cognitive impairments, bulbar symptoms accompanied by myorhythmia in the pharynx and tongue, cerebellar ataxia with tremor, motor neuron symptoms in the limbs, gastrointestinal dysfunction, orthostatic hypotension, non-rapid eye movement sleep disorder on polysomnography, and severe vocal cord palsy. Combined immunotherapy improved his symptoms, including vocal cord palsy, suggesting that combined immunotherapy might improve dysautonomia in anti-IgLON5 disease.
Language	English
Publishing date	2024-01-02
Publishing country	Japan
Document type	Journal Article
ZDB-ID	32371-8
ISSN	1349-7235 ; 0021-5120 ; 0918-2918
ISSN (online)	1349-7235
ISSN	0021-5120 ; 0918-2918
DOI	10.2169/internalmedicine.2865-23
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Article ; Online: Effect of Hydrophobic Chain Length on the Antioxidation Properties of Alanyl Tyrosine Dipeptide-type Surfactants.

Ohta, Akio / Tauchi, Yuka / Hossain, Faisal / Sawada, Yuta / Asakawa, Hitoshi / Asakawa, Tsuyoshi

Journal of oleo science

2022 Volume 71, Issue 2, Page(s) 215–222

Abstract: The antioxidant (AOX) activities of alanyl tyrosine dipeptide-type surfactants with several chain lengths were investigated. The critical micelle concentration decreased exponentially with the carbon number of the hydrophobic chain of the surfactant. The ...

Abstract	The antioxidant (AOX) activities of alanyl tyrosine dipeptide-type surfactants with several chain lengths were investigated. The critical micelle concentration decreased exponentially with the carbon number of the hydrophobic chain of the surfactant. The antioxidative property was investigated using the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid ammonium salt) (ABTS) assay and the oxygen radical absorbance capacity (ORAC) assay. The AOX activity was found to be strongly dependent on the chain length in the monomer solution. Therefore, an increase in the molecular size negatively influenced the AOX ability of the tyrosine residue. However, it was almost independent of the chain length of the surfactant in the micellar solution. The micelle particles acted as a catalyst for the reduction of the radicals in the ORAC assay.
MeSH term(s)	Antioxidants ; Carbon/chemistry ; Dipeptides/chemistry ; Dipeptides/pharmacology ; Hydrophobic and Hydrophilic Interactions ; Micelles ; Solutions ; Structure-Activity Relationship ; Surface-Active Agents/chemistry ; Surface-Active Agents/pharmacology ; Tyrosine/chemistry ; Tyrosine/pharmacology
Chemical Substances	Antioxidants ; Dipeptides ; Micelles ; Solutions ; Surface-Active Agents ; Tyrosine (42HK56048U) ; Carbon (7440-44-0)
Language	English
Publishing date	2022-02-02
Publishing country	Japan
Document type	Journal Article
ZDB-ID	2218264-0
ISSN	1347-3352 ; 1345-8957
ISSN (online)	1347-3352
ISSN	1345-8957
DOI	10.5650/jos.ess21250
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Article ; Online: A comparison of accuracy and safety between stem-first and cup-first total hip arthroplasty: a prospective randomised controlled trial.

Iwakiri, Kentaro / Ohta, Yoichi / Minoda, Yukihide / Kobayashi, Akio / Nakamura, Hiroaki

Hip international : the journal of clinical and experimental research on hip pathology and therapy

2021 Volume 33, Issue 2, Page(s) 231–240

Abstract: Background: The combined anteversion theory to prevent impingement in total hip arthroplasty (THA) has been proposed. However, because stem-anteversion is influenced by the native femoral anteversion and the stem flexion/extension angle, it is often ... ...

Abstract	Background: The combined anteversion theory to prevent impingement in total hip arthroplasty (THA) has been proposed. However, because stem-anteversion is influenced by the native femoral anteversion and the stem flexion/extension angle, it is often difficult to adjust stem anteversion during surgery. Therefore, the stem-first (combined anteversion) technique may be useful to adjust and achieve appropriate cup anteversion during surgery with respect to the implanted stem anteversion angle. However, the technique may adversely affect cup or stem angle accuracy and result in intra-operative bleeding, post-operative adverse events, and prolonged operative time. It is inconclusive whether either the stem-first or cup-first technique is safe or accurate. Therefore, this study assessed the accuracy and safety of stem-first THA compared to those of cup-first THA. Materials and methods: This prospective randomised controlled trial analysed 114 patients who were randomly divided into 2 groups (stem-first group: Results: There were no significant differences in age, gender, BMI or in the primary and secondary outcomes between the 2 groups. Conclusions: Performing stem-first in THA did not adversely affect cup and stem angle accuracy, or result in intraoperative bleeding, prolongation of operative time, or postoperative adverse events. Thus, performing stem-first may be advantageous for achieving combined anteversion theory. Trial registration: University Hospital Medical Information Network (UMIN) registration number UMIN000025189.
MeSH term(s)	Humans ; Arthroplasty, Replacement, Hip/adverse effects ; Arthroplasty, Replacement, Hip/methods ; Hip Prosthesis/adverse effects ; Prospective Studies ; Femur/surgery ; Operative Time
Language	English
Publishing date	2021-08-16
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	1162513-2
ISSN	1724-6067 ; 1120-7000
ISSN (online)	1724-6067
ISSN	1120-7000
DOI	10.1177/11207000211039767
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