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Article: Tau PET Imaging.

Higuchi, Makoto

Advances in experimental medicine and biology

2020 Volume 1184, Page(s) 217–230

Abstract: The deposition of fibrillar tau aggregates has been implicated in Alzheimer's disease (AD) and allied neurodegenerative disorders collectively referred to as tauopathies. Growing non-clinical and clinical evidence has supported intimate links between tau ...

Abstract	The deposition of fibrillar tau aggregates has been implicated in Alzheimer's disease (AD) and allied neurodegenerative disorders collectively referred to as tauopathies. Growing non-clinical and clinical evidence has supported intimate links between tau fibrillogenesis and neuronal deteriorations, rationalizing the development of imaging agents for tau fibrils to gain etiological insights into tauopathies and to facilitate diagnostic and therapeutic approaches to these diseases. Radiochemicals derived from three major chemotypes were initially applied to positron emission tomography (PET) studies of human subjects, demonstrating their utility for capturing AD-type tau deposits with reasonably high contrast. Meanwhile, these tracers suffered substantial off-target binding in the brain and did not offer sensitive detection of tau lesions in a large proportion of non-AD tauopathies. To overcome such drawbacks, 'second-generation' tau PET probes have been generated and examined in clinical settings. These tracers have enabled specific assays of AD tau pathologies, and a novel radiocompound developed by our research group has been shown to produce high contrasts for AD and non-AD tau aggregates, potentially allowing diagnostic evaluations of diverse tauopathies on an individual basis.
MeSH term(s)	Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/metabolism ; Brain/metabolism ; Humans ; Positron-Emission Tomography/methods ; Radiopharmaceuticals/metabolism ; Tauopathies/diagnostic imaging ; Tauopathies/metabolism ; tau Proteins/analysis ; tau Proteins/metabolism
Chemical Substances	Radiopharmaceuticals ; tau Proteins
Language	English
Publishing date	2020-02-20
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-981-32-9358-8_18
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Diagnostic and therapeutic targeting of pathological tau proteins in neurodegenerative disorders.

Sahara, Naruhiko / Higuchi, Makoto

FEBS open bio

2023 Volume 14, Issue 2, Page(s) 165–180

Abstract: Tauopathies, characterized by fibrillar tau accumulation in neurons and glial cells, constitute a major neuropathological category of neurodegenerative diseases. Neurofibrillary tau lesions are strongly associated with cognitive deficits in these ... ...

Abstract	Tauopathies, characterized by fibrillar tau accumulation in neurons and glial cells, constitute a major neuropathological category of neurodegenerative diseases. Neurofibrillary tau lesions are strongly associated with cognitive deficits in these diseases, but the causal mechanisms underlying tau-induced neuronal dysfunction remain unresolved. Recent advances in cryo-electron microscopy examination have revealed various core structures of tau filaments from different tauopathy patients, which can be used to classify tauopathies. In vivo visualization of tau pathology is now available using several tau positron emission tomography tracers. Among these radioprobes, PM-PBB3 allows high-contrast imaging of tau deposits in the brains of patients with diverse disorders and tauopathy mouse models. Selective degradation of pathological tau species by the ubiquitin-proteasome system or autophagy machinery is a potential therapeutic strategy. Alternatively, the non-cell-autonomous clearance of pathological tau species through neuron-glia networks could be reinforced as a disease-modifying treatment. In addition, the development of neuroinflammatory biomarkers is required for understanding the contribution of immunocompetent cells in the brain to preventing neurodegeneration. This review provides an overview of the current research and development of diagnostic and therapeutic agents targeting divergent tau pathologies.
MeSH term(s)	Mice ; Animals ; Humans ; tau Proteins/metabolism ; Cryoelectron Microscopy ; Tauopathies/drug therapy ; Tauopathies/metabolism ; Tauopathies/pathology ; Neurodegenerative Diseases/diagnosis ; Neurodegenerative Diseases/metabolism ; Brain/metabolism
Chemical Substances	tau Proteins
Language	English
Publishing date	2023-09-30
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2651702-4
ISSN	2211-5463 ; 2211-5463
ISSN (online)	2211-5463
ISSN	2211-5463
DOI	10.1002/2211-5463.13711
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Article ; Online: Determination of the erythrocyte sedimentation rate using the hematocrit-corrected aggregation index and mean corpuscular volume.

Higuchi, Makoto / Watanabe, Nobuo

Journal of clinical laboratory analysis

2023 Volume 37, Issue 6, Page(s) e24877

Abstract: Background: Determination of the erythrocyte sedimentation rate (ESR) by measurement of erythrocyte aggregation is an alternative to the Westergren method and can be performed rapidly. However, its principle is opaque and the ESR values obtained can ... ...

Abstract	Background: Determination of the erythrocyte sedimentation rate (ESR) by measurement of erythrocyte aggregation is an alternative to the Westergren method and can be performed rapidly. However, its principle is opaque and the ESR values obtained can deviate from Westergren method values (WG ESR) due to hematocrit. Furthermore, WG ESR is affected by particle size, but no studies have examined the effect of individual mean corpuscular volumes (MCVs). Methods: Simultaneous measurement of the erythrocyte aggregation index (AI) over a 5-s interval and determination of the complete blood count in 80 μL blood from 203 patients were performed (hematocrit, 21.4%-52.3%; MCV, 62.7-114.1 fL). ESR values were calculated with the hematocrit-corrected AI (HAI) for comparison with WG ESR. We improved the calculation formula by using MCV. Results: The sedimentation velocity of a single erythrocyte in the samples agreed well with an exponential function of HAI. ESR values calculated using HAI showed excellent correlation with WG ESR (r = 0.899, p < 0.001; Bland-Altman analysis: bias 2.76, limits of agreement (LOA) -24.5 to 30.0), but the difference between the calculated ESR and WG ESR increased with decreasing MCV. Calculation of ESR considering both HAI and MCV eliminated the MCV-dependent deviation and improved the correlation with WG ESR (r = 0.920, p < 0.001, bias -2.17, LOA -24.6 to 20.3). Conclusion: Calculation using HAI and MCV can rapidly provide ESR values that are highly correlated with WG ESR in clinical specimens over a wide range of hematocrit and MCV values.
MeSH term(s)	Humans ; Hematocrit ; Erythrocyte Indices ; Blood Sedimentation ; Erythrocytes
Language	English
Publishing date	2023-04-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	645095-7
ISSN	1098-2825 ; 0887-8013
ISSN (online)	1098-2825
ISSN	0887-8013
DOI	10.1002/jcla.24877
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Article ; Online: Primary care physicians working in rural areas provide a broader scope of practice: a cross-sectional study.

Kaneko, Makoto / Higuchi, Tomoya / Ohta, Ryuichi

BMC primary care

2024 Volume 25, Issue 1, Page(s) 9

Abstract: Background: Scope of practice (SoP) is an important factor for primary care physicians (PCPs). One of the strong determinants of SoP is rurality. Although Japan has several rural areas, the SoP in rural areas and the effect of rurality on SoP have not ... ...

Abstract	Background: Scope of practice (SoP) is an important factor for primary care physicians (PCPs). One of the strong determinants of SoP is rurality. Although Japan has several rural areas, the SoP in rural areas and the effect of rurality on SoP have not been investigated. This study aimed to describe SoP in Japanese primary care settings and examine the association between rurality and SoP. Methods: This cross-sectional study included PCPs in Japan. The participants were randomly sampled from the mailing list of the Japan Primary Care Association. The Scope of Practice Inventory (SPI) and Scope of Practice for Primary Care (SP4PC) were used as indicators of SoP. The Rurality Index for Japan (RIJ) was used for rurality. This study compared the number of items of SPI (total score, inpatient care, urgent care and ambulatory care) and SP4PC experienced by > 80% of all PCPs in the most urban (RIJ:1-10) and rural areas (RIJ: 91-100). A multivariable linear regression analysis was also performed to examine the relationship between the RIJ and SPI/SP4PC. Results: Of 1,000 potential participants, 299 physicians responded to the survey (response rate: 29.9%). PCPs in the most rural areas experienced a greater number of items in the inpatientl/urgent care domains of the SPI and SP4PC than those in the most urban areas. The RIJ was the only common factor for a broader SoP in both the SPI and SP4C models. The coefficients of SoP were 0.09 (95% confidence interval: 0.03-0.16) in the SPI model and 0.017 (0.005-0.03) in the SP4PC model. Conclusion: Rurality was considerably associated with SoP. The findings of this study will be helpful in understanding the SoP on rural and urban areas.
MeSH term(s)	Humans ; Cross-Sectional Studies ; Physicians, Primary Care ; Scope of Practice ; Surveys and Questionnaires ; Linear Models
Language	English
Publishing date	2024-01-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2731-4553
ISSN (online)	2731-4553
DOI	10.1186/s12875-023-02250-y
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Article: Validation of a newly developed immunoassay for TDP-43 in human plasma.

Matsuura, Sayo / Tatebe, Harutsugu / Higuchi, Makoto / Tokuda, Takahiko

Heliyon

2024 Volume 10, Issue 2, Page(s) e24672

Abstract: The level of TAR DNA-binding protein 43 (TDP-43) in human blood was reported to have potential for use as a specific fluid biomarker, which represents disease-specific pathologies, for TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS) ...

Abstract	The level of TAR DNA-binding protein 43 (TDP-43) in human blood was reported to have potential for use as a specific fluid biomarker, which represents disease-specific pathologies, for TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), which involves the aggregation and deposition of TDP-43 in the nervous system. However, at present, no reliable immunoassay can precisely quantify TDP-43 in human plasma and detect the difference in plasma TDP-43 levels between patients with ALS and controls. We recently developed a novel ultrasensitive immunoassay to quantify TDP-43 in human plasma, and in this study, we analytically validated this assay for application as a diagnostic biomarker for TDP-43 proteinopathies. The novel TDP-43 assay was assessed for the limit of detection, lower limit of quantification, intra- and interassay variation, linearity, parallelism, and analytical spike recoveries. Additionally, 17 pilot plasma samples obtained from patients with ALS and age-matched controls were analyzed using the assay. Our novel TDP-43 assay showed sufficient analytical performance to quantify TDP-43 in human plasma, with high sensitivity (LOD and LLOQ of 0.109 and 0.759 pg/mL, respectively) and high intra- and interassay precision (%CV) below 15 %. The experimental results for spike recovery, parallelism, and dilution linearity were also acceptable. In addition, despite a small sample size, significant differences in the plasma levels of TDP-43 were found between patients with ALS and controls (ALS, 66.63 ± 20.52 pg/mL; control, 42.70 ± 23.06 pg/mL, p = 0.0330). These results support that our novel TDP-43 assay is a reliable and innovative method for the quantification of TDP-43 in human plasma and can be a potential blood-based biomarker for the diagnosis of TDP-43 proteinopathies. Further large-scale studies are warranted to validate its usefulness.
Language	English
Publishing date	2024-01-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2024.e24672
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Article ; Online: COVID-19 and medical education in Japan: a struggle for fairness and transparency.

Kaneda, Yudai / Higuchi, Yuka / Yoshida, Makoto / Saito, Yoshika

International journal of medical education

2023 Volume 14, Page(s) 145–146

MeSH term(s)	Humans ; Japan ; COVID-19 ; Education, Medical
Language	English
Publishing date	2023-10-06
Publishing country	England
Document type	Letter
ISSN	2042-6372
ISSN (online)	2042-6372
DOI	10.5116/ijme.6512.8cb5
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Article ; Online: Primary care physicians working in rural areas provide a broader scope of practice

Makoto Kaneko / Tomoya Higuchi / Ryuichi Ohta

BMC Primary Care, Vol 25, Iss 1, Pp 1-

a cross-sectional study

2024 Volume 7

Abstract: Abstract Background Scope of practice (SoP) is an important factor for primary care physicians (PCPs). One of the strong determinants of SoP is rurality. Although Japan has several rural areas, the SoP in rural areas and the effect of rurality on SoP ... ...

Abstract	Abstract Background Scope of practice (SoP) is an important factor for primary care physicians (PCPs). One of the strong determinants of SoP is rurality. Although Japan has several rural areas, the SoP in rural areas and the effect of rurality on SoP have not been investigated. This study aimed to describe SoP in Japanese primary care settings and examine the association between rurality and SoP. Methods This cross-sectional study included PCPs in Japan. The participants were randomly sampled from the mailing list of the Japan Primary Care Association. The Scope of Practice Inventory (SPI) and Scope of Practice for Primary Care (SP4PC) were used as indicators of SoP. The Rurality Index for Japan (RIJ) was used for rurality. This study compared the number of items of SPI (total score, inpatient care, urgent care and ambulatory care) and SP4PC experienced by > 80% of all PCPs in the most urban (RIJ:1–10) and rural areas (RIJ: 91–100). A multivariable linear regression analysis was also performed to examine the relationship between the RIJ and SPI/SP4PC. Results Of 1,000 potential participants, 299 physicians responded to the survey (response rate: 29.9%). PCPs in the most rural areas experienced a greater number of items in the inpatientl/urgent care domains of the SPI and SP4PC than those in the most urban areas. The RIJ was the only common factor for a broader SoP in both the SPI and SP4C models. The coefficients of SoP were 0.09 (95% confidence interval: 0.03–0.16) in the SPI model and 0.017 (0.005–0.03) in the SP4PC model. Conclusion Rurality was considerably associated with SoP. The findings of this study will be helpful in understanding the SoP on rural and urban areas.
Keywords	Primary care ; Scope of practice ; Rurality ; Japan ; Medicine (General) ; R5-920
Subject code	950
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
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Article ; Online: Validation of a newly developed immunoassay for TDP-43 in human plasma

Sayo Matsuura / Harutsugu Tatebe / Makoto Higuchi / Takahiko Tokuda

Heliyon, Vol 10, Iss 2, Pp e24672- (2024)

2024

Abstract	The level of TAR DNA-binding protein 43 (TDP-43) in human blood was reported to have potential for use as a specific fluid biomarker, which represents disease-specific pathologies, for TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), which involves the aggregation and deposition of TDP-43 in the nervous system. However, at present, no reliable immunoassay can precisely quantify TDP-43 in human plasma and detect the difference in plasma TDP-43 levels between patients with ALS and controls. We recently developed a novel ultrasensitive immunoassay to quantify TDP-43 in human plasma, and in this study, we analytically validated this assay for application as a diagnostic biomarker for TDP-43 proteinopathies. The novel TDP-43 assay was assessed for the limit of detection, lower limit of quantification, intra- and interassay variation, linearity, parallelism, and analytical spike recoveries. Additionally, 17 pilot plasma samples obtained from patients with ALS and age-matched controls were analyzed using the assay. Our novel TDP-43 assay showed sufficient analytical performance to quantify TDP-43 in human plasma, with high sensitivity (LOD and LLOQ of 0.109 and 0.759 pg/mL, respectively) and high intra- and interassay precision (%CV) below 15 %. The experimental results for spike recovery, parallelism, and dilution linearity were also acceptable. In addition, despite a small sample size, significant differences in the plasma levels of TDP-43 were found between patients with ALS and controls (ALS, 66.63 ± 20.52 pg/mL; control, 42.70 ± 23.06 pg/mL, p = 0.0330). These results support that our novel TDP-43 assay is a reliable and innovative method for the quantification of TDP-43 in human plasma and can be a potential blood-based biomarker for the diagnosis of TDP-43 proteinopathies. Further large-scale studies are warranted to validate its usefulness.
Keywords	TDP-43 ; Plasma biomarker ; Immunoassay ; Validation ; Amyotrophic lateral sclerosis ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Subject code	610
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: A rapid and accurate method for estimating the erythrocyte sedimentation rate using a hematocrit-corrected optical aggregation index.

Higuchi, Makoto / Watanabe, Nobuo

PloS one

2022 Volume 17, Issue 7, Page(s) e0270977

Abstract: Although both the erythrocyte sedimentation rate (ESR) and optically measured erythrocyte aggregation parameters are affected by the hematocrit, this interaction is not considered by the method used to estimate ESR that considers aggregation parameters. ... ...

Abstract	Although both the erythrocyte sedimentation rate (ESR) and optically measured erythrocyte aggregation parameters are affected by the hematocrit, this interaction is not considered by the method used to estimate ESR that considers aggregation parameters. In this study, we investigated the relationship between the ESR obtained by the Westergren method and that obtained with an aggregation parameter, namely, the aggregation index (AI) of multiple hematocrit values and fibrinogen-spiked samples with an analysis time of 5-60 s, and attempted to develop a rapid and accurate ESR estimation method. The AIs obtained from 5- and 10-s optical measurements with a fixed hematocrit were highly correlated with the erythrocyte sedimentation velocity. Furthermore, the rate of the AI increase with an increasing hematocrit was not significantly affected by the fibrinogen concentration at these measurement times. On the basis of these results, we defined the hematocrit-corrected aggregation index (HAI). The exponential function of the HAI obtained from the 5-s measurement agreed well with the sedimentation velocity calculated to eliminate the effect of hindered settling, and the HAI and hematocrit could be used to calculate the time constant of the sedimentation curve with a linear regression equation. The ESR value at 1 h was calculated based on the modified Stokes' law and the HAI obtained from the 5-s measurement and showed an excellent correlation (R = 0.966) with the ESR value obtained by the Westergren method over a wide range of hematocrit and fibrinogen concentrations.
MeSH term(s)	Blood Sedimentation ; Erythrocyte Aggregation ; Erythrocytes ; Fibrinogen ; Hematocrit
Chemical Substances	Fibrinogen (9001-32-5)
Language	English
Publishing date	2022-07-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0270977
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Article ; Online: Rhododendrol, a reductive metabolite of raspberry ketone, suppresses the differentiation of 3T3‑L1 cells into adipocytes.

Uramaru, Naoto / Kawashima, Azusa / Osabe, Makoto / Higuchi, Toshiyuki

Molecular medicine reports

2023 Volume 27, Issue 2

Abstract: Obesity is a serious medical condition worldwide, and a major risk factor for type 2 diabetes, metabolic syndrome, cancer and cardiovascular disease. In addition to changes in dietary habits and physical activity, consuming supplements to maintain good ... ...

Abstract	Obesity is a serious medical condition worldwide, and a major risk factor for type 2 diabetes, metabolic syndrome, cancer and cardiovascular disease. In addition to changes in dietary habits and physical activity, consuming supplements to maintain good health and prevent obesity is important in modern society. Raspberry ketone (RK) is a natural phenolic ketone found in the European red raspberry (
MeSH term(s)	Animals ; Humans ; Mice ; 3T3-L1 Cells ; Adipocytes/cytology ; Adipocytes/metabolism ; Adipogenesis/drug effects ; Butanols/pharmacology ; CCAAT-Enhancer-Binding Protein-alpha/metabolism ; Obesity/prevention & control ; PPAR gamma/genetics ; PPAR gamma/metabolism ; Anti-Obesity Agents/pharmacology
Chemical Substances	Butanols ; CCAAT-Enhancer-Binding Protein-alpha ; PPAR gamma ; raspberry ketone (7QY1MH15BG) ; rhododendrol (12QWN45UL0) ; Anti-Obesity Agents
Language	English
Publishing date	2023-01-12
Publishing country	Greece
Document type	Journal Article
ZDB-ID	2469505-1
ISSN	1791-3004 ; 1791-2997
ISSN (online)	1791-3004
ISSN	1791-2997
DOI	10.3892/mmr.2023.12938
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