1.Macrophage Paracrine Signalling Differentially Affects Fibroblast-Induced Collagenous Tissue Remodelling
Hannah F. M. BROUWER ; Amal K. MANSOOR ; Sylvia DEKKER ; Carlijn V. C. BOUTEN ; Keita ITO ; Jasper FOOLEN ; Anthal I. P. M. SMITS
Tissue Engineering and Regenerative Medicine 2026;23(1):125-142
BACKGROUND:
Upon injury, tissue repair often leads to a loss in functionality, organisation, and structure. The immune system, particularly macrophages, is crucial during tissue healing. Macrophages polarise into pro-inflammatory M1 and anti-inflammatory M2 subsets, regulating various stages of tissue healing. Macrophages steer fibroblasts in the process of extracellular matrix degradation, synthesis, and rearrangement. However, the direct role of paracrine signalling by different macrophage phenotypes on fibroblast-induced structural tissue remodelling remains elusive. Therefore, this study aimed to explore how paracrine factors from M1, M2a, and M2c macrophages affect fibroblast remodelling abilities in an in vitro model system.
METHODS:
Macrophages were polarised in vitro, and their conditioned medium or cytokine-enriched medium containing specific macrophage-secreted factors was added to fibroblast-populated reconstituted collagen tissues.
RESULTS:
Macrophage-conditioned media led to changes in fibroblast-induced tissue compaction for all macrophage subsets. The presence of macrophage polarising factors in the conditioned medium, particularly LPS/IFNc, and high serum levels directly affected tissue compaction and matrix remodelling gene expression. Without these confounding factors, M1 cytokine-enriched medium led to reduced tissue compaction when compared to M2a/M2c cytokine-enriched media. MMP activity analysis showed that matrix degradation likely contributed to tissue compaction.
CONCLUSION
Factors secreted by M1 macrophages resulted in reduced tissue compaction compared to M2a/M2c macrophages in an in vitro model of tissue remodelling, suggesting a diminished capacity for fibroblasts to remodel the extracellular matrix. Importantly, factors to polarize macrophages and serum are regarded as confounding factors in studying the effect of paracrine signalling by macrophages on tissue remodelling.
2.Initial Experiences of Total Body Irradiation Using Radixact
Keita SAKAI ; Tatsuya HASEGAWA ; Ken SHISHIDO ; Yuta OMI ; Yoshiyuki ITO ; Arisa TAKEUCHI
Journal of the Japanese Association of Rural Medicine 2025;73(5):434-440
A new radiation system known as the TomoTherapy Radixact X9 was introduced at our hospital in June 2021. From August 2021 to March 2022, 6 patients underwent total body irradiation (TBI) with tomotherapy with the Radixact X9. This paper describes the sequence of events from treatment planning computed tomography to irradiation. Results are also reported for measurements made with Gafchromic EBT3 film, the Delta4 Phantom+, and an A1SL ionization chamber dosimeter, set-up error, and time required to enter and exit the room, which were measured during plan verification. The measurement results were as follows: Gafchromic EBT3 film, 91.78±0.96% ; Delta4 Phantom+ head, 100±0% ; chest, 98.93±1.17% ; foot, 98.90±2.28% ; ionization chamber dosimeter A1SL, -0.39±0.70%; Residual error: -0.01±1.91 mm for lateral, 0.29±1.60 mm for longitudinal, 0.36±2.07 mm for vertical, -0.06±0.78° for roll. In addition, the time required to enter and exit the room was 98.50±17.17 min. TBI could be performed within set-up error of 5 mm in all cases. The validation results from the initial 6 cases confirmed that TBI with tomotherapy provided good dose distribution and positional accuracy.
3.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.
4.Relationship between Lower Limb Pain Intensity and Dynamic Lumbopelvic-Hip Alignment in Patients with Degenerative Lumbar Spinal Canal Stenosis: A Cross-Sectional Study
Takuya MIURA ; Ryoji TOMINAGA ; Keita SATO ; Tatsuya ENDO ; Masumi IWABUCHI ; Toshikazu ITO ; Osamu SHIRADO
Asian Spine Journal 2022;16(6):918-926
Methods:
Thirty patients with LSS scheduled for spine surgery participated in this study. Lower limb pain was assessed using the Visual Analog Scale (VAS), and the patients were divided into two groups based on the mean scores (patients with scores above and below the mean were classified as the high-VAS and low-VAS groups, respectively). The kinematics of the spine, pelvis, and hip joints during gait were then measured using a 3D motion analysis system. Student paired t -tests were used to compare the angles of the spine, pelvis, and hip during gait between the two groups.
Results:
Compared to those in the low-VAS group, the spine was significantly extended and bent toward the more painful lower limb side, and the pelvis was significantly anteriorly tilted among individuals in the high-VAS group.
Conclusions
Patients with LSS experiencing severe pain in their lower limb tend to keep the spine in a more extended position, bend laterally toward the painful side, and have an anteriorly tilted pelvic posture. The dynamic spinal and pelvic alignment was closely related to the intensity of the lower limb pain.
5.Hip Extensor Strength Influences Dynamic Postural Changes during Gait in Patients with Adult Spinal Deformity: A Cross-Sectional Study Using Three-Dimensional Motion Analysis
Keita SATO ; Ryoji TOMINAGA ; Tatsuya ENDO ; Takuya MIURA ; Masumi IWABUCHI ; Toshikazu ITO ; Osamu SHIRADO
Asian Spine Journal 2022;16(5):643-650
Methods:
Thirty patients with ASD aged ≥50 years who were admitted to our hospital between July 2016 and September 2019 were included in this study. X-ray parameters (i.e., sagittal vertical axis, pelvic tilt, and pelvic incidence minus lumbar lordosis) were evaluated from the full-length standing radiographs of the subjects. Trunk and hip extensor strength was evaluated using a hand-held dynamometer. Dynamic postural changes (i.e., sagittal trunk shift during standing, sagittal trunk shift during gait, and delta sagittal trunk shift) were assessed using a three-dimensional motion analysis system. The relationships between dynamic postural change and various X-ray parameters, as well as trunk and hip extensor strength, were examined using multivariable analysis.
Results:
Multivariable analysis showed that hip extensor strength is the factor most strongly associated with dynamic postural change among the X-ray parameters and physical functions assessed in this study (β=−0.41, R2=0.12).
Conclusions
We demonstrated the association between dynamic postural change and hip extensor strength in patients with ASD. Our results may be useful to healthcare providers treating patients with ASD. Interventions for dynamic postural change in patients with ASD should focus on hip extensor strength.
6.Therapeutic Endoscopic Treatment Plus Maintenance Dimethyl Sulfoxide Therapy Prolongs Recurrence-Free Time in Patients With Hunner Type Interstitial Cystitis: A Pilot Study
Atsushi OTSUKA ; Takahisa SUZUKI ; Yuto MATSUSHITA ; Hiromitsu WATANABE ; Keita TAMURA ; Daisuke MOTOYAMA ; Toshiki ITO ; Takayuki SUGIYAMA ; Hideaki MIYAKE
International Neurourology Journal 2019;23(4):327-333
PURPOSE: To evaluate whether hydrodistention with fulguration of Hunner lesions (HD/FUL) plus maintenance dimethyl sulfoxide (DMSO) therapy prolongs the recurrence-free time in patients with Hunner type interstitial cystitis (IC).METHODS: The study enrolled patients with Hunner type IC who required repeat HD/FUL due to recurrence of IC symptoms after the first HD/FUL at our institution. All patients received a second HD/FUL plus maintenance DMSO therapy. The maintenance DMSO therapy was performed every 2 weeks for a total of 8 instillations, and then once every 4 weeks thereafter. The recurrencefree time from HD/FUL to therapeutic failure was estimated using the Kaplan-Meier method. The recurrence-free time between the first HD/FUL and second HD/FUL plus maintenance DMSO therapy was statistically compared using the log-rank test.RESULTS: A total of 21 patients (mean age, 66.3±10.8 years) with Hunner type IC were evaluated. The recurrence-free time for the second HD/FUL plus maintenance DMSO therapy was significantly longer than that for the first HD/FUL (P<0.0001). The median recurrence-free time for the first HD/FUL was 10.1 months, while that for the second HD/FUL plus maintenance DMSO therapy has yet to be reached. The recurrence-free rate for the first HD/FUL was 81.0% at 6 months, 38.1% at 1 year, 9.5% at 2 years, and 4.8% at 3 years. In contrast, the rate for the second HD/FUL plus maintenance DMSO therapy was 100% at 6 months, 94.7% at 1 year, 82.6% at 2 years, and 82.6% at 3 years. There were no significant differences in efficacy between the first and second HD/FUL.CONCLUSIONS: HD/FUL plus maintenance DMSO therapy clearly prolongs the recurrence-free time compared with HD/FUL alone in Hunner type IC.
Cystitis, Interstitial
;
Dimethyl Sulfoxide
;
Humans
;
Methods
;
Pilot Projects
;
Recurrence
7.Influence of Helicobacter pylori Infection on Endoscopic Findings of Gastric Adenocarcinoma of the Fundic Gland Type
Fumiaki ISHIBASHI ; Keita FUKUSHIMA ; Takashi ITO ; Konomi KOBAYASHI ; Ryu TANAKA ; Ryoichi ONIZUKA
Journal of Gastric Cancer 2019;19(2):225-233
PURPOSE: Gastric adenocarcinoma of the fundic gland type (chief cell predominant type) (GA-FG-CCP) was first reported as a rare adenocarcinoma found in the normal fundic mucosa. Recent studies have proposed the possibility that GA-FG-CCPs were also generated in the atrophic mucosa after Helicobacter pylori (HP) eradication therapy. However, little is known on the endoscopic findings of GA-FG-CCP generated in the atrophic mucosa due to its extreme rarity. MATERIALS AND METHODS: A total of 8 patients who underwent endoscopic submucosal resection and were diagnosed with GA-FG-CCP generated in the HP-uninfected mucosa (4 cases, HP-uninfected group) or HP-eradicated atrophic mucosa (4 cases, HP-eradicated group) were retrospectively analyzed, and their endoscopic findings, including magnifying endoscopy with narrow band imaging (M-NBI), and pathological features were compared. RESULTS: While GA-FG-CCPs in the 2 groups displayed similar macroscopic appearance, M-NBI demonstrated that characteristic microvessels (tapered microvessels like withered branches) were specifically identified in the HP-eradicated group. Pathological investigation revealed that a decreasing number of fundic glands and thinned foveolar epithelium covering tumor ducts were thought to lower the thickness of the covering layer over tumor ducts in the HP-eradicated group. Moreover, dilation of vessels just under the surface of the lesions contributed to the visualization of microvessels by M-NBI. CONCLUSIONS: The change in background mucosa due to HP infection influenced the thickness of the covering layer over the tumor ducts and M-NBI finding of GA-FG-CCP.
Adenocarcinoma
;
Endoscopy
;
Epithelium
;
Helicobacter pylori
;
Helicobacter
;
Humans
;
Microvessels
;
Mucous Membrane
;
Narrow Band Imaging
;
Retrospective Studies
;
Stomach Neoplasms
8.Simultaneous Three-Dimensional Analysis of Cervical Spine Kinematics in the Axial and Sagittal Views during a Simulated Frontal Impact: Differences between Tensed and Relaxed States.
Keita NAKAYAMA ; Masataka SAKANE ; Susumu EJIMA ; Daisuke ITO ; Tomofumi NISHINO ; Sou KITAJIMA ; Masashi YAMAZAKI
Asian Spine Journal 2015;9(6):876-883
STUDY DESIGN: Prospective experimental study on humans. PURPOSE: To determine whether postural differences during a low-speed impact are observed in the sagittal and axial views, particularly in a relaxed state. OVERVIEW OF LITERATURE:: Three-dimensional motion capture systems have been used to analyze posture and head-neck-torso kinematics in humans during a simulated low-speed impact, yet little research has focused on the axial view. Since a seatbelt asymmetrically stabilizes a drivers right shoulder and left lower waist into the seat, it potentially creates movement in the axial view. METHODS: Three healthy adult men participated in the experimental series, which used a low-speed sled system. The acceleration pulse created a full sine shape with a maximum acceleration of 8.0 m/s2 at 500 ms, during which the kinematics were evaluated in relaxed and tensed states. The three-dimensional motion capture system used eight markers to record and analyze body movement and head-neck-torso kinematics in the sagittal and axial views during the low-speed impact. Head and trunk rotation angles were also calculated. RESULTS: Larger movements were observed in the relaxed than in the tensed state in the sagittal view. The cervical and thoracic spine flexed and extended, respectively, in the relaxed state. In the axial view, larger movements were also observed in the relaxed state than in the tensed state, and the left shoulder rotated. CONCLUSIONS: During simulated frontal impact, the rotation angle between the head and trunk was significantly larger in the relaxed state. Therefore, we recommend also observing movement in the axial view during impact tests.
Acceleration
;
Adult
;
Biomechanical Phenomena*
;
Head
;
Humans
;
Imaging, Three-Dimensional
;
Male
;
Posture
;
Prospective Studies
;
Shoulder
;
Spine*
;
Transcutaneous Electric Nerve Stimulation*
9.An Autopsy Case of Bilateral Tension Pneumothorax after Acupuncture
Kimiharu IWADATE ; Haruo ITO ; Seiko KATSUMURA ; Nagahisa MATSUYAMA ; Keita SATO ; Isamu YONEMURA ; Yohko ITO
Journal of the Japan Society of Acupuncture and Moxibustion 2004;54(2):137-141
Acupuncture is one of the most popular complementary therapies in the world. Pneumothorax due to perforation of the lungs by needle insertion is one of the most common and serious complications of acupuncture treatment. Although there have been several case studies of pneumothorax induced by acupuncture, as far as we know there have been no reports on the pathological findings of autopsy cases.
In this report, we describe the pathological findings of an autopsy case of bilateral tension pneumothorax after acupuncture. The patient suffered dyspnea and chest pain soon the completionof an acupuncture treatment, and died 90 min later. Several ecchymoses were macroscopically observed on the parietal pleura in the left and right thoracic cavity, suggesting that needles were inserted into the thoracic cavity and that the lungs were perforated. The many black spots we observed on the parietal pleura along the vertebral column microscopically consisted of a number of dust-like black pigments and macrophages containing these pigments. These spots seemed to have appeared because of the previous insertion of needles.


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