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Article ; Online: The role of free fatty acid receptor-1 in gastric contractions in

Huang, Jin / Suzuki, Miu / Endo, Ami / Watanabe, Ayumi / Sakata, Ichiro

2024 Volume 15, Issue 4, Page(s) 2221–2233

Abstract: Motilin is an important hormonal regulator in the migrating motor complex (MMC). Free fatty acid receptor-1 (FFAR1, also known as GPR40) has been reported to stimulate motilin release in human duodenal organoids. However, how FFAR1 regulates gastric ... ...

Abstract	Motilin is an important hormonal regulator in the migrating motor complex (MMC). Free fatty acid receptor-1 (FFAR1, also known as GPR40) has been reported to stimulate motilin release in human duodenal organoids. However, how FFAR1 regulates gastric motility
MeSH term(s)	Humans ; Animals ; Gastrointestinal Motility ; Fatty Acids, Nonesterified/pharmacology ; Motilin/metabolism ; Motilin/pharmacology ; Myoelectric Complex, Migrating/physiology ; Stomach/physiology ; Shrews/metabolism
Chemical Substances	Fatty Acids, Nonesterified ; Motilin (52906-92-0)
Language	English
Publishing date	2024-02-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2612033-1
ISSN	2042-650X ; 2042-6496
ISSN (online)	2042-650X
ISSN	2042-6496
DOI	10.1039/d3fo03565d
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Article ; Online: A highly sensitive PCR method for A1 allele detection in A2 milk samples without DNA isolation.

Watanabe, Ayumi / Munakata, Kyo / Muto, Miyabi / Kuramoto, Takashi

Animal science journal = Nihon chikusan Gakkaiho

2023 Volume 94, Issue 1, Page(s) e13846

Abstract: We previously developed a genotyping method to detect the A1 and A2 alleles of the bovine β-casein gene. This method required DNA extraction from hair samples. Recently, demand for A2 milk (milk from cows homozygous for the A2 allele) has increased, and ... ...

Abstract	We previously developed a genotyping method to detect the A1 and A2 alleles of the bovine β-casein gene. This method required DNA extraction from hair samples. Recently, demand for A2 milk (milk from cows homozygous for the A2 allele) has increased, and dairy farms are required to have certification to produce A2 milk. Here, we describe the development of a new, simple, and sensitive genotyping method for the β-casein gene that does not require DNA extraction. This method uses the CycleavePCR technique and can amplify the β-casein gene directly from raw milk samples. Genotypes obtained from the milk samples (n = 27) were completely coincident with those obtained from genomic DNA. In addition, this method could quantify the A1 allele in the milk samples. The limit of detection for the A1 allele in A2 milk was 2%. The copy numbers of the A1 allele corresponding to the 2% detection limit were estimated to be 30.5 ± 24.3 molecules/μL. These findings indicate that this new genotyping method is simple and fast for detecting the A1 allele in milk samples and can therefore be potentially used to certify A2 milk.
MeSH term(s)	Female ; Animals ; Cattle/genetics ; Alleles ; Caseins/genetics ; Milk ; Polymerase Chain Reaction/veterinary ; Farms
Chemical Substances	Caseins
Language	English
Publishing date	2023-06-24
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2095161-9
ISSN	1740-0929 ; 1344-3941
ISSN (online)	1740-0929
ISSN	1344-3941
DOI	10.1111/asj.13846
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Article ; Online: Phenotypic and functional characterization of posoleucel, a multivirus-specific T cell therapy for the treatment and prevention of viral infections in immunocompromised patients.

Vasileiou, Spyridoula / Kuvalekar, Manik / Velazquez, Yovana / Watanabe, Ayumi / Leen, Ann M / Gilmore, Sarah A

Cytotherapy

2024

Abstract: Background: Deficits in T cell immunity translate into increased risk of severe viral infection in recipients of solid organ and hematopoietic cell transplants. Thus, therapeutic strategies that employ the adoptive transfer of virus-specific T cells are ...

Abstract	Background: Deficits in T cell immunity translate into increased risk of severe viral infection in recipients of solid organ and hematopoietic cell transplants. Thus, therapeutic strategies that employ the adoptive transfer of virus-specific T cells are being clinically investigated to treat and prevent viral diseases in these highly immunocompromised patients. Posoleucel is an off-the-shelf multivirus-specific T cell investigational product for the treatment and prevention of infections due to adenovirus, BK virus, cytomegalovirus, Epstein-Barr virus, human herpesvirus 6 or JC virus. Methods: Herein we perform extensive characterization of the phenotype and functional profile of posoleucel to illustrate the cellular properties that may contribute to its in vivo activity. Results and conclusions: Our results demonstrate that posoleucel is enriched for central and effector memory CD4
Language	English
Publishing date	2024-03-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2039821-9
ISSN	1477-2566 ; 1465-3249
ISSN (online)	1477-2566
ISSN	1465-3249
DOI	10.1016/j.jcyt.2024.03.012
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Article ; Online: Involvement of the autonomic nervous system in colonic contractions in conscious Suncus murinus.

Suzuki, Miu / Watanabe, Ayumi / Huang, Jin / Kobayashi, Yuki / Sakata, Ichiro

Neurogastroenterology and motility

2023 Volume 36, Issue 2, Page(s) e14716

Abstract: Background: Colonic motility is regulated by various factors along the gut-brain axis; however, detailed mechanisms are unknown. This study aimed to examine the involvement of the autonomic nervous system in colonic motility. Suncus murinus (suncus) is ... ...

Abstract	Background: Colonic motility is regulated by various factors along the gut-brain axis; however, detailed mechanisms are unknown. This study aimed to examine the involvement of the autonomic nervous system in colonic motility. Suncus murinus (suncus) is a small laboratory mammal suitable for gastrointestinal motility studies. Methods: Colonic motility and concomitant feeding and defecation behaviors in vagotomized and reserpine-administered suncus were recorded simultaneously for 24 h. Furthermore, we performed immunohistochemistry on tyrosine hydroxylase (TH) and in situ hybridization on corticotropin-releasing hormone (CRH) in suncus brain. Additionally, we examined c-Fos expression in the brain using immunohistochemistry in conscious suncus with colorectal distension. Key results: In vagotomized suncus, clustered giant migrating contractions (GMCs), consisting of strong contractions occurring in a short time, were observed, and the percentage of GMCs without defecation increased. The frequency of GMCs in the reserpine-administered suncus increased during a light period (ZT0-4, 4-8) and decreased during a dark period (ZT16-20, 20-24) compared to a vehicle group. Additionally, the percentage of GMCs without defecation in the reserpine-administered suncus increased. Suncus TH-immunopositive neurons were found in the locus coeruleus (LC), as shown in rodents. In contrast, CRH mRNA-expressing cells were not observed in a region assumed to be the Barrington's nucleus (Bar). Furthermore, colorectal distension in conscious suncus induced c-Fos expression in LC TH neurons. Conclusions & inferences: Our results suggest that the vagus and sympathetic nerves are not required for induction of GMCs in vivo. However, they are likely to exert a modulatory role in control of GMC frequency in Suncus murinus.
MeSH term(s)	Animals ; Reserpine ; Vagus Nerve/physiology ; Gastrointestinal Motility/physiology ; Consciousness ; Corticotropin-Releasing Hormone ; Colorectal Neoplasms ; Mammals
Chemical Substances	Reserpine (8B1QWR724A) ; Corticotropin-Releasing Hormone (9015-71-8)
Language	English
Publishing date	2023-11-29
Publishing country	England
Document type	Journal Article
ZDB-ID	1186328-6
ISSN	1365-2982 ; 1350-1925
ISSN (online)	1365-2982
ISSN	1350-1925
DOI	10.1111/nmo.14716
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Article: Gallium citrate-67 single-photon emission computed tomography/computed tomography for localizing the foci of classic fever and inflammation of unknown origin: A retrospective study of diagnostic yield.

Tsuzuki, Seiichiro / Watanabe, Ayumi / Iwata, Mitsunaga / Toyama, Hiroshi / Terasawa, Teruhiko

Asia Oceania journal of nuclear medicine & biology

2021 Volume 9, Issue 2, Page(s) 111–122

Abstract: Objectives: Only few studies have assessed the use of gallium citrate-67 single-photon emission computed tomography/computed tomography (: Methods: We retrospectively assessed the medical records of 27 adult patients with FUO/IUO who had an ... ...

Abstract	Objectives: Only few studies have assessed the use of gallium citrate-67 single-photon emission computed tomography/computed tomography ( Methods: We retrospectively assessed the medical records of 27 adult patients with FUO/IUO who had an unsuccessful diagnostic workup and who underwent Results: Almost all patients completed the recommended diagnostic workup, except for urine culture and abdominal ultrasonography. Moreover, prior to Conclusion: 67
Language	English
Publishing date	2021-05-31
Publishing country	Iran
Document type	Journal Article
ZDB-ID	2724313-8
ISSN	2322-5726 ; 2322-5718
ISSN (online)	2322-5726
ISSN	2322-5718
DOI	10.22038/AOJNMB.2020.53188.1364
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Article ; Online: Predictors of Diagnostic Contributions and Spontaneous Remission of Symptoms Associated with Positron Emission Tomography with Fluorine-18-Fluorodeoxy Glucose Combined with Computed Tomography in Classic Fever or Inflammation of Unknown Origin: a Retrospective Study.

Tsuzuki, Seiichiro / Watanabe, Ayumi / Iwata, Mitsunaga / Toyama, Hiroshi / Terasawa, Teruhiko

Journal of Korean medical science

2021 Volume 36, Issue 22, Page(s) e150

Abstract: Background: In patients with fever or inflammation of unknown origin (fever of unknown origin [FUO] or inflammation of unknown origin [IUO], respectively), expert consensus recommends the use of positron emission tomography with fluorine-18-fluorodeoxy ... ...

Abstract	Background: In patients with fever or inflammation of unknown origin (fever of unknown origin [FUO] or inflammation of unknown origin [IUO], respectively), expert consensus recommends the use of positron emission tomography with fluorine-18-fluorodeoxy glucose combined with computed tomography (FDG-PET/CT) when standard work-up fails to identify diagnostic clues. However, the clinical variables associated with successful localization of the cause by FDG-PET/CT remain uncertain. Moreover, the long-term outcomes of patients with unexplained FUO or IUO after negative FDG-PET/CT results are unknown. Therefore, we assessed predictors of successful diagnosis of FUO or IUO caused by FDG-PET/CT and associations of spontaneous remission of symptoms with FDG-PET/CT results. Methods: All patients with FUO or IUO, who underwent FDG-PET/CT from 2013 to 2019 because diagnostic work-up failed to identify a cause, were retrospectively included. We calculated the diagnostic yield and performed multivariable logistic regression to assess characteristics previously proposed to be associated with successful localization of FUO or IUO causes. We also assessed whether the FDG-PET/CT results were associated with spontaneous remissions. Results: In total, 50 patients with diagnostically challenging FUO or IUO (35 with FUO and 15 with IUO) were assessed. Other than one case of infection, all the identified causes were either malignancy or non-infectious inflammatory diseases (each with 18 patients), and FDG-PET/CT correctly localized the cause in 29 patients (diagnostic yield = 58%). None of the proposed variables was associated with successful localization. All 13 patients with sustained unexplained cause remained alive (median follow-up, 190 days). Spontaneous remission was observed in 4 of 5 patients with a negative FDG-PET/CT, and 1 of 8 with a positive result ( Conclusion: In the current cohort, the proposed variables were not predictive for successful localization by FDG-PET/CT. A negative FDG-PET/CT scan may be prognostic for spontaneous remission in patients with sustained FUO or IUO.
MeSH term(s)	Adult ; Fever of Unknown Origin/diagnosis ; Fever of Unknown Origin/diagnostic imaging ; Fever of Unknown Origin/mortality ; Fluorodeoxyglucose F18/administration & dosage ; Humans ; Infections/complications ; Inflammation/diagnosis ; Inflammation/diagnostic imaging ; Inflammation/mortality ; Male ; Middle Aged ; Neoplasms/complications ; Neoplasms/pathology ; Positron Emission Tomography Computed Tomography/adverse effects ; Positron Emission Tomography Computed Tomography/methods ; Remission, Spontaneous ; Retrospective Studies ; Tomography, X-Ray Computed
Chemical Substances	Fluorodeoxyglucose F18 (0Z5B2CJX4D)
Language	English
Publishing date	2021-06-07
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	639262-3
ISSN	1598-6357 ; 1011-8934
ISSN (online)	1598-6357
ISSN	1011-8934
DOI	10.3346/jkms.2021.36.e150
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Article ; Online: T cell immune profiling of respiratory syncytial virus for the development of a targeted immunotherapy.

Papayanni, Penelope Georgia / Koukoulias, Kiriakos / Kuvalekar, Manik / Watanabe, Ayumi / Velazquez, Yovana / Ramos, Carlos A / Leen, Ann M / Vasileiou, Spyridoula

British journal of haematology

2023 Volume 202, Issue 4, Page(s) 874–878

Abstract: Respiratory syncytial virus (RSV)-associated viral infections are a major public health problem affecting the immunologically naïve/compromised populations. Given the RSV-associated morbidity and the limited treatment options, we sought to characterize ... ...

Abstract	Respiratory syncytial virus (RSV)-associated viral infections are a major public health problem affecting the immunologically naïve/compromised populations. Given the RSV-associated morbidity and the limited treatment options, we sought to characterize the cellular immune response to RSV to develop a targeted T cell therapy for off-the-shelf administration to immunocompromised individuals. Here we report on the immunological profiling, as well as manufacturing, characterization and antiviral properties of these RSV-targeted T cells. A randomized, phase 1/2 clinical trial evaluating their safety and activity in haematopoietic stem cell transplant recipients as an off-the-shelf multi-respiratory virus-directed product is currently underway (NCT04933968, https://clinicaltrials.gov).
MeSH term(s)	Humans ; Antiviral Agents/therapeutic use ; Immunotherapy ; Respiratory Syncytial Virus Infections/drug therapy ; Respiratory Syncytial Virus, Human ; T-Lymphocytes
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2023-06-15
Publishing country	England
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.18933
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Article ; Online: Targeting IDH2R140Q and other neoantigens in acute myeloid leukemia.

Leung, Wingchi K / Torres Chavez, Alejandro G / French-Kim, Matthew / Shafer, Paul / Mamonkin, Maksim / Hill, LaQuisa C / Kuvalekar, Manik / Velazquez, Yovana / Watanabe, Ayumi / Watanabe, Norihiro / Hoyos, Valentina / Lulla, Premal / Leen, Ann M

Blood

2024 Volume 143, Issue 17, Page(s) 1726–1737

Abstract: Abstract: For patients with high-risk or relapsed/refractory acute myeloid leukemia (AML), allogeneic stem cell transplantation (allo-HSCT) and the graft-versus-leukemia effect mediated by donor T cells, offer the best chance of long-term remission. ... ...

Abstract	Abstract: For patients with high-risk or relapsed/refractory acute myeloid leukemia (AML), allogeneic stem cell transplantation (allo-HSCT) and the graft-versus-leukemia effect mediated by donor T cells, offer the best chance of long-term remission. However, the concurrent transfer of alloreactive T cells can lead to graft-versus-host disease that is associated with transplant-related morbidity and mortality. Furthermore, ∼60% of patients will ultimately relapse after allo-HSCT, thus, underscoring the need for novel therapeutic strategies that are safe and effective. In this study, we explored the feasibility of immunotherapeutically targeting neoantigens, which arise from recurrent nonsynonymous mutations in AML and thus represent attractive targets because they are exclusively present on the tumor. Focusing on 14 recurrent driver mutations across 8 genes found in AML, we investigated their immunogenicity in 23 individuals with diverse HLA profiles. We demonstrate the immunogenicity of AML neoantigens, with 17 of 23 (74%) reactive donors screened mounting a response. The most immunodominant neoantigens were IDH2R140Q (n = 11 of 17 responders), IDH1R132H (n = 7 of 17), and FLT3D835Y (n = 6 of 17). In-depth studies of IDH2R140Q-specific T cells revealed the presence of reactive CD4+ and CD8+ T cells capable of recognizing distinct mutant-specific epitopes restricted to different HLA alleles. These neo-T cells could selectively recognize and kill HLA-matched AML targets endogenously expressing IDH2R140Q both in vitro and in vivo. Overall, our findings support the clinical translation of neoantigen-specific T cells to treat relapsed/refractory AML.
MeSH term(s)	Humans ; Antigens, Neoplasm/immunology ; Antigens, Neoplasm/genetics ; Hematopoietic Stem Cell Transplantation ; Immunotherapy/methods ; Isocitrate Dehydrogenase/genetics ; Isocitrate Dehydrogenase/immunology ; Leukemia, Myeloid, Acute/immunology ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/therapy ; Mutation
Chemical Substances	Antigens, Neoplasm ; IDH1 protein, human (EC 1.1.1.42.) ; IDH2 protein, human (EC 1.1.1.41) ; Isocitrate Dehydrogenase (EC 1.1.1.41)
Language	English
Publishing date	2024-01-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2023021979
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Article ; Online: Assessment of the cytolytic potential of a multivirus-targeted T cell therapy using a vital dye-based, flow cytometric assay.

Koukoulias, Kiriakos / Papayanni, Penelope G / Jones, Julia / Kuvalekar, Manik / Watanabe, Ayumi / Velazquez, Yovana / Gilmore, Sarah / Papadopoulou, Anastasia / Leen, Ann M / Vasileiou, Spyridoula

Frontiers in immunology

2023 Volume 14, Page(s) 1299512

Abstract: Reliable and sensitive characterization assays are important determinants of the successful clinical translation of immunotherapies. For the assessment of cytolytic potential, the chromium 51 ( ...

Abstract	Reliable and sensitive characterization assays are important determinants of the successful clinical translation of immunotherapies. For the assessment of cytolytic potential, the chromium 51 (
MeSH term(s)	Humans ; Epstein-Barr Virus Infections ; Herpesvirus 4, Human ; Adenoviridae ; BK Virus ; Cell- and Tissue-Based Therapy
Language	English
Publishing date	2023-12-22
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1299512
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Article ; Online: Longitudinal analysis of the evolution of cellular immunity to SARS-CoV-2 induced by infection and vaccination.

Vasileiou, Spyridoula / Kuvalekar, Manik / Velazquez, Yovana / Watanabe, Ayumi / Narula, Mansi / Workineh, Aster G / French-Kim, Matthew / Chavez, Alejandro Torres / Gilmore, Sarah / Rooney, Cliona M / Leen, Ann M

Haematologica

2023 Volume 108, Issue 7, Page(s) 1934–1939

MeSH term(s)	Humans ; SARS-CoV-2 ; COVID-19/prevention & control ; Immunity, Cellular ; Vaccination ; Antibodies, Viral
Chemical Substances	Antibodies, Viral
Language	English
Publishing date	2023-07-01
Publishing country	Italy
Document type	Letter
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2022.281947
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