1.Peripheral blood mitochondrial DNA copy number as a predictor of steatotic liver disease development: insights from epidemiological and experimental studies.
Genki MIZUNO ; Atsushi TESHIGAWARA ; Hiroya YAMADA ; Eiji MUNETSUNA ; Yoshiki TSUBOI ; Yuji HATTORI ; Mirai YAMAZAKI ; Yoshitaka ANDO ; Itsuki KAGEYAMA ; Takuya WAKASUGI ; Naohiro ICHINO ; Keisuke OSAKABE ; Keiko SUGIMOTO ; Ryosuke FUJII ; Hiroaki ISHIKAWA ; Nobutaka OHGAMI ; Koji OHASHI ; Koji SUZUKI
Environmental Health and Preventive Medicine 2025;30():42-42
BACKGROUND:
Mitochondria, which harbor their own genome (mtDNA), have attracted attention due to the potential of mtDNA copy number (mtDNA-CN) as an indicator of mitochondrial dysfunction. Although mtDNA-CN has been proposed as a simple and accessible biomarker for metabolic disorders such as metabolic dysfunction-associated steatotic liver disease, the underlying mechanisms and the causal relationship remain insufficiently elucidated. In this investigation, we combined longitudinal epidemiological data, animal studies, and in vitro assays to elucidate the potential causal relationship between reduced mtDNA-CN and the development of steatotic liver disease (SLD).
METHODS:
We conducted a longitudinal study using data from a health examination cohort initiated in 1981 in Yakumo, Hokkaido, Japan. Data from examinations performed in 2015 and 2022 were analyzed, focusing on 76 subjects without SLD at baseline (2015) to assess the association between baseline mtDNA-CN and subsequent risk of SLD development. In addition, 28-day-old SD rats were fed ad libitum on a 45% high-fat diet and dissected at 2 and 8 weeks of age. Blood and liver mtDNA-CN were measured and compared at each feeding period. Additionally, in vitro experiments were performed using HepG2 cells treated with mitochondrial function inhibitors to induce mtDNA-CN depletion and to examine its impact on intracellular lipid accumulation.
RESULTS:
Epidemiological analysis showed that the subjects with low mtDNA-CN had a significantly higher odds ratio for developing SLD compared to high (odds ratio [95% confidence interval]: 4.93 [1.08-22.50]). Analysis of the animal model showed that 8 weeks of high-fat diet led to the development of fatty liver and a significant decrease in mtDNA-CN. A further 2 weeks of high-fat diet consumption resulted in a significant decrease in hepatic mtDNA-CN, despite the absence of fatty liver development, and a similar trend was observed for blood. Complementary in vitro experiments revealed that pharmacologically induced mitochondrial dysfunction led to a significant reduction in mtDNA-CN and was associated with increases in intracellular lipid accumulation in HepG2 cells.
CONCLUSIONS
Our findings suggest that reduced mtDNA-CN may contribute causally to SLD development and could serve as a convenient, noninvasive biomarker for early detection and risk assessment.
Animals
;
DNA, Mitochondrial/genetics*
;
Humans
;
Male
;
DNA Copy Number Variations
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Female
;
Fatty Liver/blood*
;
Rats
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Middle Aged
;
Longitudinal Studies
;
Rats, Sprague-Dawley
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Adult
;
Japan/epidemiology*
;
Aged
;
Biomarkers/blood*
;
Hep G2 Cells
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Diet, High-Fat/adverse effects*
2.Effect of number of college baseball pitching on movement, performance, physical strength, physiological, and psychological functions of pitchers
Hiroshi YAMADA ; Keita OGAWARA ; Shuichi UCHIYAMA ; Eiji ITO ; Michinori MIYAZAKI ; Seiji MIYAZAKI
Japanese Journal of Physical Fitness and Sports Medicine 2023;72(3):201-213
This study aimed to examine the effects of college baseball pitching on movement, performance, physical strength, and physiological and psychological functions of pitchers. The participants were 10 right-handed male pitchers from the University baseball team. The number of pitches were 15 per inning and 135 per nine innings. Ball speed and accuracy were measured for each pitching. The grip strength, back muscle strength, and standing long jump were measured before and after all pitches. Blood lactate levels were measured before pitching, at the end of the 5th and 7th innings, and at 3rd, 6th, and 9th minutes after pitching. The participant’s heart rate and subjective exercise intensity were measured at the beginning and end of each inning using the Borg scale measurement. Five high-speed cameras were used to capture the pitching motions. The displacement of the center of gravity, lower and upper limb joint angles, and the speed of each segment were calculated. The baseball speed and accuracy did not change with the increased number of pitches. However, the grip strength decreased. Although blood lactate and heart rate were not altered, subjective exercise intensity was increased. The lower limb kinematics remained unchanged; however, elbow height was reduced in the upper limb. These results suggest that highly competitive pitchers experience subjective fatigue with the increased number of pitches, however, they maintain pitch performance, speed, and accuracy without altering whole-body physiology and lower-body function and form.
3.Can Conventional Magnetic Resonance Imaging Substitute Three-Dimensional Magnetic Resonance Imaging in the Diagnosis of Lumbar Foraminal Stenosis?
Maruf Mohammad HASIB ; Kentaro YAMADA ; Masatoshi HOSHINO ; Eiji YAMADA ; Koji TAMAI ; Shinji TAKAHASHI ; Akinobu SUZUKI ; Hiromitsu TOYODA ; Hidetomi TERAI ; Hiroaki NAKAMURA
Asian Spine Journal 2021;15(4):472-480
Methods:
We investigated 154 foramina at L5–S1 in 77 patients. All the patients had degenerative lumbar disorders and had undergone both conventional MRI and 3D-MRI during the same visit. Differences between the FSRs calculated from conventional and 3D-MRI reconstructions and any correlations with the plain radiography findings were assessed.
Results:
In foramina that had a FSR of <50% on conventional MRI, the difference between the FSR obtained using conventional MRI and 3D-MRI was 5.1%, with a correlation coefficient of 0.777. For foramina with a FSR ≥50% on conventional MRI, the difference was 20.2%, with a correlation coefficient of 0.54. FSR obtained using 3D-MRI was significantly greater in patients who required surgery than in those who were successfully treated with conservative methods (88% and 42%, respectively). Segments with spondylolisthesis or lateral wedging showed higher FSRs than those without these conditions on both types of MRI.
Conclusions
FSRs <50% obtained using conventional MRI were sufficiently reliable; however, the results were inaccurate for FSRs ≥50%. Patients with high FSRs on 3D-MRI were more likely to require surgical treatment. Therefore, 3D-MRI is recommended in patients with suspected stenosis detected using conventional MRI or plain radiographs.
4.Can Conventional Magnetic Resonance Imaging Substitute Three-Dimensional Magnetic Resonance Imaging in the Diagnosis of Lumbar Foraminal Stenosis?
Maruf Mohammad HASIB ; Kentaro YAMADA ; Masatoshi HOSHINO ; Eiji YAMADA ; Koji TAMAI ; Shinji TAKAHASHI ; Akinobu SUZUKI ; Hiromitsu TOYODA ; Hidetomi TERAI ; Hiroaki NAKAMURA
Asian Spine Journal 2021;15(4):472-480
Methods:
We investigated 154 foramina at L5–S1 in 77 patients. All the patients had degenerative lumbar disorders and had undergone both conventional MRI and 3D-MRI during the same visit. Differences between the FSRs calculated from conventional and 3D-MRI reconstructions and any correlations with the plain radiography findings were assessed.
Results:
In foramina that had a FSR of <50% on conventional MRI, the difference between the FSR obtained using conventional MRI and 3D-MRI was 5.1%, with a correlation coefficient of 0.777. For foramina with a FSR ≥50% on conventional MRI, the difference was 20.2%, with a correlation coefficient of 0.54. FSR obtained using 3D-MRI was significantly greater in patients who required surgery than in those who were successfully treated with conservative methods (88% and 42%, respectively). Segments with spondylolisthesis or lateral wedging showed higher FSRs than those without these conditions on both types of MRI.
Conclusions
FSRs <50% obtained using conventional MRI were sufficiently reliable; however, the results were inaccurate for FSRs ≥50%. Patients with high FSRs on 3D-MRI were more likely to require surgical treatment. Therefore, 3D-MRI is recommended in patients with suspected stenosis detected using conventional MRI or plain radiographs.
5.Long-term Outcomes of One Stage Surgery Using Transanal Colorectal Tube for Acute Colorectal Obstruction of Stage II/III Distal Colon Cancer
Yusuke OKUDA ; Tomonori YAMADA ; Yoshikazu HIRATA ; Takaya SHIMURA ; Ryuzo YAMAGUCHI ; Eiji SAKAMOTO ; Satoshi SOBUE ; Takahiro NAKAZAWA ; Hiromi KATAOKA ; Takashi JOH
Cancer Research and Treatment 2019;51(2):474-482
PURPOSE: Since oncological outcomes of transanal colorectal tube (TCT) placement, an endoscopic treatment for colorectal cancer (CRC) with acute colorectal obstruction (ACO), remain unknown, this study analyzed long-term outcomes of TCT placement for stage II/III CRC with ACO. MATERIALS AND METHODS: Data were retrospectively reviewed from consecutive patients with distal stage II/III CRC who underwent surgery between January 2007 and December 2011 at two Japanese hospitals. One hospital conducted emergency surgery and the other performed TCT placement as the standard treatment for all CRCs with ACO. Propensity score (PS) matching was used to adjust baseline characteristics between two groups. RESULTS: Among 754 patients with distal stage II/III CRC, 680 did not have ACO (non-ACO group) and 74 had ACO (ACO group). The PS matching between both hospitals identified 234 pairs in the non-ACO group and 23 pairs in the ACO group. In the non-ACO group, the surgical quality was equivalent between the two institutions, with no significant differences in overall survival (OS) and disease-free survival (DFS). In the ACO group, the rate of primary resection/anastomosis was higher in the TCT group than in the surgery group (87.0% vs. 26.1%, p < 0.001). No significant differences were noted between the surgery and the TCT groups in OS (5-year OS, 61.9% vs. 51.5%; p=0.490) and DFS (5-year DFS, 45.9% vs. 38.3%; p=0.658). CONCLUSION: TCT placement can achieve similar long-term outcomes to emergency surgery, with a high rate of primary resection/anastomosis for distal stage II/III colon cancer with ACO.
Asian Continental Ancestry Group
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Colon
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Colonic Neoplasms
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Colorectal Neoplasms
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Disease-Free Survival
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Emergencies
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Humans
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Propensity Score
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Retrospective Studies
6.Impact of fatty pancreas and lifestyle on the development of subclinical chronic pancreatitis in healthy people undergoing a medical checkup.
Makoto FUJII ; Yuko OHNO ; Makoto YAMADA ; Yoshihiro KAMADA ; Eiji MIYOSHI
Environmental Health and Preventive Medicine 2019;24(1):10-10
BACKGROUND:
Although fat accumulation in human organs is associated with a variety of diseases, there is little evidence about the effect of a fatty pancreas on the development of subclinical chronic pancreatitis over the clinical course.
METHODS:
We conducted a prospective cohort study from 2008 to 2014 of patients who underwent a medical checkup consultation for fat accumulated in the pancreas. Patients included in the analysis were divided into a non-fatty pancreas group (n = 9710) and fatty pancreas group (n = 223). The primary end point was the odds ratio (OR) for chronic pancreatitis associated with fatty pancreas, which was diagnosed using ultrasonography. We used a multiple logistic regression model to estimate the OR and the corresponding 95% confidence interval (CI).
RESULTS:
Ninety-two people were diagnosed with chronic pancreatitis, including both presumptive and definitive diagnoses. Twelve people were diagnosed with chronic pancreatitis by ultrasonography among the 223 patients with fatty pancreas, and 80 patients among 9710 were diagnosed with non-fatty pancreas. The crude OR was 6.85 (95% CI 3.68, 12.75), and the multiple adjusted OR was 3.96 (95% CI 2.04, 7.66).
CONCLUSIONS
Fat accumulation in the pancreas could be a risk factor for developing subclinical chronic pancreatitis.
Adipose Tissue
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diagnostic imaging
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pathology
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Adult
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Alcohol Drinking
;
epidemiology
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Female
;
Humans
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Japan
;
epidemiology
;
Life Style
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Logistic Models
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Male
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Middle Aged
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Pancreas
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diagnostic imaging
;
pathology
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Pancreatitis, Chronic
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diagnosis
;
epidemiology
;
etiology
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Physical Examination
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Prospective Studies
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Risk Factors
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Smoking
;
epidemiology
7.Clinical Effects of Steam Rock Bathing in Saiboku Hot Spring for Allergic Rhinitis
Shizuo SASAZAKI ; Eiji YAMADA ; Hitoshi KURABAYASHI ; Akiko HISHINUMA ; Jun’ichi TAMURA ; Kazuo KUBOTA
The Journal of The Japanese Society of Balneology, Climatology and Physical Medicine 2017;80(2):73-79
Background: Hot spring inhalation and rock bathing are widely practiced in Europe, and immersion in water up to the shoulders is popular in Japanese balneotherapy. We designed a combination therapy of steam rock bathing and immersion in an open-air hot spring pool for allergic rhinitis.Methods: Data were obtained by anonymous questionnaires from 19 participants with perennial allergic rhinitis who underwent the combination therapy for several days during the spring-pollen season. The participants immersed themselves in a sitting position in Saiboku hot spring water (sodium salt hot spring) at 41°C up to the shoulder level for 10 min in the open-air and then lay on a floor paved with small rocks in a supine position for 20 min in a room filled with the steam from hot springs, then immersed themselves again in the hot spring water for 10 min, and finally rested and sat on a chair for 20 min in a comfortable room. The hot spring water circulated through tubes with small holes that were embedded under the floor, which was paved with small rocks consisting of tourmaline and lime stones. Steam from the hot spring water penetrated through the floor and vaporized in the room. The rock bathing room was 40°C in temperature and 75% in humidity.Results: Clinical symptoms were alleviated in 17 of 19 participants. Watery rhinorrhea, eye itching, sneeze, and sore throat were improved in 100%, 75%, 40%, and 100% of the participants, respectively, compared with symptoms during the previous several years. No adverse effects were observed in any participants. Conclusion: Steam rock bathing, combined with immersion in an open-air hot spring pool, is useful in ameliorating the focal and systemic symptoms of allergic rhinitis.
9.Early Effect of Single-dose Sitagliptin Administration on Gastric Emptying: Crossover Study Using the 13C Breath Test.
Takashi NONAKA ; Yusuke SEKINO ; Hiroshi IIDA ; Eiji YAMADA ; Hidenori OHKUBO ; Eiji SAKAI ; Takuma HIGURASHI ; Kunihiro HOSONO ; Hiroki ENDO ; Tomoko KOIDE ; Hirokazu TAKAHASHI ; Koji FUJITA ; Masato YONEDA ; Ayumu GOTO ; Akihiko KUSAKABE ; Noritoshi KOBAYASHI ; Eiji GOTOH ; Shin MAEDA ; Atsushi NAKAJIMA ; Chihiro NOSAKA ; Masahiko INAMORI
Journal of Neurogastroenterology and Motility 2013;19(2):227-232
BACKGROUND/AIMS: The gastrointestinal motility effects of endogenous incretin hormones enhanced by dipeptidyl peptidase-IV (DPP-IV) inhibitors have not yet been sufficiently investigated. The aim of this study was to determine whether single pre-prandial sitagliptin, the DPP-IV inhibitor, administration might have an effect on the rate of liquid gastric emptying using the 13C-acetic acid breath test. METHODS: Ten healthy male volunteers participated in this randomized, two-way crossover study. The subjects fasted for overnight and were randomly assigned to receive 50 mg sitagliptin 2 hours before ingestion of the liquid test meal (200 kcal per 200 mL, containing 100 mg 13C-acetate) or the test meal alone. Under both conditions, breath samples were collected for 150 minutes following the meal. Liquid gastric emptying was estimated by the values of the following parameters: the time required for 50% emptying of the labeled meal (T1/2), the analog to the scintigraphy lag time for 10% emptying of the labeled meal (Tlag), the gastric emptying coefficient and the regression-estimated constants (beta and kappa), calculated by using the 13CO2 breath excretion curve using the conventional formulae. The parameters between the 2 test conditions were compared statistically. RESULTS: No significant differences in the calculated parameters, including T1/2, Tlag, gastric emptying coefficient or beta and kappa, were observed between the 2 test conditions. CONCLUSIONS: The present study revealed that single-dose sitagliptin intake had no significant influence on the rate of liquid gastric emptying in asymptomatic volunteers.
Breath Tests
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Cross-Over Studies
;
Eating
;
Gastric Emptying
;
Gastrointestinal Motility
;
Humans
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Incretins
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Male
;
Meals
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Pyrazines
;
Triazoles
;
Sitagliptin Phosphate
10.Visceral Obesity as a Risk Factor for Left-Sided Diverticulitis in Japan: A Multicenter Retrospective Study.
Eiji YAMADA ; Hidenori OHKUBO ; Takuma HIGURASHI ; Eiji SAKAI ; Hiroki ENDO ; Hirokazu TAKAHASHI ; Eri UCHIDA ; Emi TANIDA ; Nobuyoshi IZUMI ; Akira KANESAKI ; Yasuo HATA ; Tetsuya MATSUURA ; Nobutaka FUJISAWA ; Kazuto KOMATSU ; Shin MAEDA ; Atsushi NAKAJIMA
Gut and Liver 2013;7(5):532-538
BACKGROUND/AIMS: Left-sided diverticulitis is increasing in Japan, and many studies report that left-sided diverticulitis is more likely to be severe. Therefore, it is important to identify the features and risk factors for left-sided diverticulitis. We hypothesized that left-sided diverticulitis in Japan is related to obesity and conducted a study of the features and risk factors for this disorder in Japan. METHODS: Right-sided diverticulitis and left-sided diverticulitis patients (total of 215) were compared with respect to background, particularly obesity-related factors to identify risk factors for diverticulitis. RESULTS: There were 166 (77.2%) right-sided diverticulitis patients and 49 (22.8%) left-sided diverticulitis patients. The proportions of obese patients (body mass index > or =25 kg/m2, p=0.0349), viscerally obese patients (visceral fat area > or =100 cm2, p=0.0019), patients of mean age (p=0.0003), and elderly patients (age > or =65 years, p=0.0177) were significantly higher in the left-sided-diverticulitis group than in the right-sided-diverticulitis group. The proportion of viscerally obese patients was significantly higher in the left-sided-diverticulitis group than in the left-sided-diverticulosis group (p=0.0390). CONCLUSIONS: This study showed that obesity, particularly visceral obesity, was a risk factor for left-sided diverticulitis in Japan.
Aged
;
Diverticulitis
;
Humans
;
Japan
;
Obesity
;
Obesity, Abdominal
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Retrospective Studies
;
Risk Factors


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