Publications by authors named "Takahiro Suzuki"

533 Publications

Abundant Synthesis of Netrin-1 in Satellite Cell-Derived Myoblasts Isolated from EDL Rather Than Soleus Muscle Regulates Fast-Type Myotube Formation.

Int J Mol Sci 2021 Apr 26;22(9). Epub 2021 Apr 26.

Laboratory of Cell and Tissue Biology, Research Faculty of Agriculture, Graduate School of Agriculture, Hokkaido University, Kita 9, Nishi 9, Kita-ku, Sapporo 060-8589, Japan.

Resident myogenic stem cells (satellite cells) are attracting attention for their novel roles in myofiber type regulation. In the myogenic differentiation phase, satellite cells from soleus muscle (slow fiber-abundant) synthesize and secrete higher levels of semaphorin 3A (Sema3A, a multifunctional modulator) than those derived from extensor digitorum longus (EDL; fast fiber-abundant), suggesting the role of Sema3A in forming slow-twitch myofibers. However, the regulatory mechanisms underlying fast-twitch myotube commitment remain unclear. Herein, we focused on netrin family members (netrin-1, -3, and -4) that compete with Sema3A in neurogenesis and osteogenesis. We examined whether netrins affect fast-twitch myotube generation by evaluating their expression in primary satellite cell cultures. Initially, netrins are upregulated during myogenic differentiation. Next, we compared the expression levels of netrins and their cell membrane receptors between soleus- and EDL-derived satellite cells; only netrin-1 showed higher expression in EDL-derived satellite cells than in soleus-derived satellite cells. We also performed netrin-1 knockdown experiments and additional experiments with recombinant netrin-1 in differentiated satellite cell-derived myoblasts. Netrin-1 knockdown in myoblasts substantially reduced fast-type myosin heavy chain (MyHC) expression; exogenous netrin-1 upregulated fast-type MyHC in satellite cells. Thus, netrin-1 synthesized in EDL-derived satellite cells may promote myofiber type commitment of fast muscles.
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http://dx.doi.org/10.3390/ijms22094499DOI Listing
April 2021

Three-dimensional histological explanation of the dermoscopy patterns in acral melanocytic lesions.

J Dermatol 2021 Apr 27. Epub 2021 Apr 27.

Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Dermoscopic images of pigmented lesions have distinct features on the sole where skin ridges and furrows exist. Pigmentation of benign nevus usually locates on the skin furrow, while the malignant melanoma is pigmented on the skin ridge. Correspondence between dermoscopy and pathology in the pigmented lesions on soles have been studied based on conventional vertical pathological images. However, for the full understanding of the correspondence, observation of horizontal histological images would be required, because the epidermis constructs unique horizontal structures, namely crista profunda limitans, crista profunda intermedia, and transverse ridge. In this study, we analyzed basic dermoscopic images of the representative acral melanocytic lesions (nevus, lentigo, and malignant melanoma) by horizonal histological images. We created serial horizontal pathological images by digital reconstruction of a hundred of serial vertical images. We could show that parallel furrow pattern is created by the pigmentation of crista profunda limitans, parallel ridge pattern by the pigmentation of both of crista profunda limitans and crista profunda intermediate, and lattice-like pattern by the pigmentation of transverse ridge. Our results would be useful for the intuitive histological understanding of dermoscopy.
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http://dx.doi.org/10.1111/1346-8138.15907DOI Listing
April 2021

Switching From Pregabalin to Mirogabalin in Patients with Peripheral Neuropathic Pain: A Multi-Center, Prospective, Single-Arm, Open-Label Study (MIROP Study).

Pain Ther 2021 Apr 15. Epub 2021 Apr 15.

Department of Anesthesiology and Pain Medicine, Juntendo University Faculty of Medicine, 3-1-3 Hongo, Bunkyo-ku, Tokyo, 113-8431, Japan.

Introduction: Mirogabalin, which is a selective ligand of the αδ subunit of voltage-gated Ca channels, was recently approved in Japan for peripheral neuropathic pain. The αδ ligands, including mirogabalin and pregabalin, are associated with significant risk of adverse events (AEs) such as somnolence or dizziness, leading to poor compliance and subsequent inefficacy. Safety and efficacy data for switching patients from pregabalin to mirogabalin are scarce.

Methods: This prospective, single-arm, open-label study involving ten participating centers in Japan recruited patients aged ≥ 20 years with peripheral neuropathic pain [visual analog scale (VAS) score ≥ 40 mm]. Where necessary, patients underwent a 1-week tapering period to reduce their pregabalin dose, after which pregabalin was stopped and mirogabalin dose was increased using a step-wise dose titration. Patients underwent dose increases after the first and second weeks if there were no tolerability issues, followed by the effective doses until the end of the study (4 weeks). The primary endpoint was the incidence of somnolence, dizziness, and peripheral edema; secondary endpoints included changes in VAS score. AEs were monitored for safety.

Results: Of 157 patients who provided informed consent, 152 patients were enrolled; 136 (89.5%) patients completed the study. The overall incidences of somnolence, dizziness, and peripheral edema were 41.4, 15.8, and 2.6%, respectively. Most patients (> 70%) experienced mild AEs, and one patient experienced a severe AE (dizziness). Most patients (> 70%) were able to achieve dose titration to an effective dose. Overall mean VAS score significantly decreased (Δ15.7 mm, p < 0.0001) by the end of the study.

Conclusions: Mirogabalin switching from pregabalin is well tolerated and effective in pain management for peripheral neuropathic pain using a step-wise titration.

Trial Registration: Japan Registry of Clinical Trials (jRCTs031190113).
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http://dx.doi.org/10.1007/s40122-021-00255-yDOI Listing
April 2021

Compliance with a physical activity guideline among junior high school students.

Pediatr Int 2021 Mar 31. Epub 2021 Mar 31.

Physical Activity for Health Group, School of Psychological, Sciences and Health, University of Strathclyde, 50 George Street, Glasgow, G1 1QE, UK.

Background: There was no nation-wide moderate- to vigorous-intensity physical activity (MVPA) data among Japanese adolescents. This study assessed the compliance with the MVPA guideline in adolescents using a random sampling survey in Japan. The factors associated with meeting the guideline were also examined.

Methods: Participants were 1st to 3rd grade Japanese junior high school students (307 boys and 255 girls). We analyzed data of the National Sports-Life Survey of Teens 2019 which used the Japanese version of PA questions in the WHO Health Behaviour in School-aged Children survey and potential correlates of MVPA.

Results: The compliance with meeting PA guideline by the WHO for Japanese students was 19.0% (95% CI, 15.8 - 22.3). The compliance for boys was significantly higher than that of girls (23.1%; 95% CI, 18.4 - 27.8; vs, 14.1%; 95% CI, 9.8 -18.4). Meeting PA guideline was significantly associated with boys in the second grade than boys in the first grade (OR 1.78; 95% CI, 1.02 - 3.09), liking PA (for all: OR 2.97; 95% CI, 1.32 - 6.69; for girls: OR 2.99; 95% CI, 1.01 - 8.81), and sports participation (for all: OR 4.77; 95% CI, 2.32 - 9.80; for boys: OR 6.00; 95% CI, 1.81 - 19.89; for girls: OR 4.08; 95% CI, 1.63 - 10.21).

Conclusion: The results suggest that more than 80% junior high school students were insufficiently physically active in Japan. Preference for PA and sports participation may be important correlates of sufficient PA.
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http://dx.doi.org/10.1111/ped.14716DOI Listing
March 2021

A cyclic lipopeptide surfactin is a species-selective Hsp90 inhibitor that suppresses cyanobacterial growth.

J Biochem 2021 Mar 26. Epub 2021 Mar 26.

Department of Cell and Developmental Biology, Graduate School of Biostudies, Kyoto University, Kyoto, 606-8502, Japan.

Heat shock protein 90 (Hsp90) is essential for eukaryotic cells, whereas bacterial homologs play a role under stresses and in pathogenesis. Identifying species-specific Hsp90 inhibitors is challenging because Hsp90 is evolutionarily conserved. We found that a cyclic lipopeptide surfactin inhibits the ATPase activity of Hsp90 from the cyanobacterium Synechococcus elongatus (S. elongatus) PCC 7942 but does not inhibit Escherichia coli (E. coli), yeast and human Hsp90s. Molecular docking simulations indicated that surfactin could bind to the N-terminal dimerization interface of the cyanobacterial Hsp90 in the ATP- and ADP-bound states, which provided molecular insights into the species-selective inhibition. The data suggest that surfactin inhibits a rate-limiting conformational change of S. elongatus Hsp90 in the ATP hydrolysis. Surfactin also inhibited the interaction of the cyanobacterial Hsp90 with a model substrate, and suppressed S. elongatus growth under heat stress, but not that of E. coli. Surfactin did not show significant cellular toxicity toward mammalian cells. These results indicate that surfactin inhibits the cellular function of Hsp90 specifically in the cyanobacterium. The present study shows that a cyclic peptide has a great specificity to interact with a specific homolog of a highly conserved protein family.
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http://dx.doi.org/10.1093/jb/mvab037DOI Listing
March 2021

Extravascular leakage of induction doses of rocuronium: four cases in which both depth of neuromuscular block and plasma concentration of rocuronium were assessed.

J Clin Monit Comput 2021 Mar 21. Epub 2021 Mar 21.

Department of Anesthesiology, Nihon University School of Medicine, 30-1, Oyaguchi Kamimachi, Itabashi-Ku, Tokyo, 173-8610, Japan.

The duration of action of extravasated rocuronium varies depending on the patient's comorbidities. In patients who receive high doses of non-depolarizing neuromuscular blocking agents subcutaneously, anesthesiologists should be aware of unexpected prolongation of the progress and recovery of neuromuscular block. In such cases, the depth and recovery of neuromuscular block should be objectively monitored to avoid residual neuromuscular block and recurarization.
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http://dx.doi.org/10.1007/s10877-021-00692-2DOI Listing
March 2021

Epigenetic effects induced by the ectopic expression of Pax7 in 3T3-L1.

J Biochem 2021 Mar 17. Epub 2021 Mar 17.

Alaa Elgaabari, Atsuko Miyawaki-Kuwakado, Kosuke Tomimatsu, Qianmei Wu, Kosuke Tokunaga, Wakana Izumi, Takahiro Suzuki, Ryuichi Tatsumi, Mako Nakamura.

Although skeletal muscle cells and adipocytes are derived from the same mesoderm, they do not transdifferentiate in vivo and are strictly distinct at the level of gene expression. To elucidate some of the regulatory mechanisms underlying this strict distinction, Pax7, a myogenic factor, was ectopically expressed in 3T3-L1 adipose progenitor cells to perturb their adipocyte differentiation potential. Transcriptome analysis showed that ectopic expression of Pax7 repressed the expression of some adipocyte genes and induced expression of some skeletal muscle cell genes. We next profiled the epigenomic state altered by Pax7 expression using H3K27ac, an activating histone mark, and H3K27me3, a repressive histone mark, as indicators. Our results show that ectopic expression of Pax7 did not result in the formation of H3K27ac at loci of skeletal muscle-related genes, but instead resulted in the formation of H3K27me3 at adipocyte-related gene loci. These findings suggest that the primary function of ectopic Pax7 expression is the formation of H3K27me3, and muscle gene expression results from secondary regulation.
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http://dx.doi.org/10.1093/jb/mvab030DOI Listing
March 2021

Anesthetic management for mastectomy and total hysterectomy in a 49-year-old woman with type 1 sialidosis: a case report.

JA Clin Rep 2021 Mar 4;7(1):20. Epub 2021 Mar 4.

Department of Anesthesiology, Nihon University School of Medicine, 30-1 Oyaguchi, Kamimachi, Itabashi-ku, Tokyo, 173-8610, Japan.

Background: Sialidosis is an autosomal recessive glycoprotein storage disorder, caused by neuraminidase deficiency which leads to abnormal intracellular accumulation and urinary excretion of sialylated oligosaccharides, resulting in various morphological and functional disorders. Only a few reports have described the anesthetic managements of patients with sialidosis.

Case Presentation: A 49-year-old woman with type 1 sialidosis suffered from all limb contractures, an ocular cherry-red spot, and myoclonic seizures of the limbs. She had been cognitively normal. She was separately scheduled for mastectomy under total intravenous anesthesia and total hysterectomy under combined general and epidural anesthesia uneventfully.

Conclusions: Our patient with type 1 sialidosis received both general and epidural anesthesia uneventfully. Anesthesiologists should carefully assess patients with sialidosis and give careful consideration to individually tailored anesthetic managements.
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http://dx.doi.org/10.1186/s40981-021-00425-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933293PMC
March 2021

Prolonged onset and duration of action of rocuronium after accidental subcutaneous injection in a patient with chronic renal failure-a case report.

JA Clin Rep 2021 Feb 27;7(1):18. Epub 2021 Feb 27.

Department of Anesthesiology, Nihon University, School of Medicine, 30-1, Oyaguchi, Kami-cho, Itabashi-ku, Tokyo, 173-8610, Japan.

Background: Drugs administered subcutaneously have delayed onset and prolonged duration of action versus those given intravenously. Since the duration of action of rocuronium is prolonged in patients with renal dysfunction, subcutaneous administration of rocuronium to such patients might significantly prolong its effect.

Case Presentation: A 51-year-old female with chronic renal failure was accidentally administered 1.04 mg/kg rocuronium subcutaneously. Marked prolongation of onset and duration of action of rocuronium were detected on acceleromyography. Slow development of the neuromuscular block was still observed at 100 min after injection. Administration of 4.5 mg/kg sugammadex at 140 min after rocuronium injection facilitated recovery from a train-of-four (TOF) count of 2 to a TOF ratio of 100% within 5 min. No symptoms of postoperative recurarization and upper airway obstruction were observed.

Conclusion: Neuromuscular monitoring is necessary to evaluate the progress and depth of neuromuscular block, particularly when rocuronium is inadvertently administered subcutaneously.
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http://dx.doi.org/10.1186/s40981-021-00421-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914319PMC
February 2021

Evaluation of the modified Crohn's disease activity index in patients with Crohn disease with enterostomy: A single-center observational study.

Medicine (Baltimore) 2021 Feb;100(6):e24717

First Department of Medicine.

Abstract: Although the Crohn's Disease Activity Index (CDAI) is often used to evaluate the disease activity in Crohn's disease (CD), the number of liquid or soft stools cannot be precisely evaluated, and thus accurate scores cannot be calculated, in patients with enterostomy. Therefore, we created the modified CDAI (mCDAI), without the defecation frequency item from the CDAI, and examined its usefulness.Study participants comprised 9 patients with CD with enterostomy and 20 patients with CD without enterostomy. Correlations between the mCDAI and serum albumin (Alb) levels or C-reactive protein (CRP) levels were examined using regression analysis. Additionally, regression analyses were conducted in patients with CD without enterostomy to determine the Alb and CRP levels corresponding to the CDAI at its cutoff value for remission status (150). The obtained values were applied to the mCDAI regression equations to determine the equivalent mCDAI cutoff value.mCDAI and Alb levels were significantly negatively correlated (P < .0001). The mCDAI had a significant positive correlation with the CRP level and erythrocyte sedimentation rate (P = .0061 and P = .0133, respectively). From the regression analysis of patients with CD without enterostomy, the Alb and CRP levels equivalent to a CDAI of 150 were 3.85 g/dL and 0.62 mg/dL, respectively. When applying these values to the mCDAI regression formulas, the values of 113.8 and 115.2, respectively, were obtained. Thus, the cutoff value of the mCDAI indicating disease activity was estimated as 115.The mCDAI fully reflects the nutritional status and inflammatory response, and is convenient and useful for assessing disease activity over time, in patients with CD with enterostomy. A mCDAI score ≥ 115 indicates disease activity.
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http://dx.doi.org/10.1097/MD.0000000000024717DOI Listing
February 2021

Evaluation of Tibial Tunnel Location with the Femoral Tunnel Created Behind the Resident's Ridge in Transtibial Anterior Cruciate Ligament Reconstruction.

J Knee Surg 2021 Jan 22. Epub 2021 Jan 22.

Department of Orthopaedic Surgery, Jichi Medical University, Shimotsuke, Japan.

Few studies have determined whether a femoral bone tunnel could be created behind the resident's ridge by using a transtibial (TT) technique-single bundle (SB)-anterior cruciate ligament (ACL) reconstruction. The aim of this study was to clarify (1) whether it is possible to create a femoral bone tunnel behind the resident's ridge by using the TT technique with SB ACL reconstruction, (2) to define the mean tibial and femoral tunnel angles during anatomic SB ACL reconstruction, and (3) to clarify the tibial tunnel inlet location when the femoral tunnel is created behind resident's ridge. Arthroscopic TT-SB ACL reconstruction was performed on 36 patients with ACL injuries. The point where 2.4-mm guide pin was inserted was confirmed, via anteromedial portal, to consider a location behind the resident's ridge. Then, an 8-mm diameter femoral tunnel with a 4.5-mm socket was created. Tunnel positions were evaluated by using three-dimensional computed tomography (3D-CT) 1 week postoperatively. Quadrant method and the resident's ridge on 3D-CT were evaluated to determine whether femoral tunnel position was anatomical. Radiological evaluations of tunnel positions yielded mean ( ±  standard deviation) X- and Y-axis values for the tunnel centers: femoral tunnel, 25.2% ± 5.1% and 41.6% ± 10.2%; tibial tunnel, 49.2% ± 3.5%, and 31.5% ± 7.7%. The bone tunnels were anatomically positioned in all cases. The femoral tunnel angle relative to femoral axis was 29.4 ± 5.5 degrees in the coronal view and 43.5 ± 8.0 degrees in the sagittal view. The tibial tunnel angle relative to tibial axis was 25.5 ± 5.3 degrees in the coronal view and 52.3 ± 4.6 degrees in the sagittal view. The created tibial bone tunnel inlet had an average distance of 13.4 ± 2.7 mm from the medial tibial joint line and 9.7 ± 1.7 mm medial from the axis of the tibia. Femoral bone tunnel could be created behind the resident's ridge with TT-SB ACL reconstruction. The tibial bone tunnel inlet averaged 13.4 mm from the medial tibial joint line and 9.7 mm medial from the tibia axis.
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http://dx.doi.org/10.1055/s-0040-1722568DOI Listing
January 2021

Adverse effects of LPS on membrane proteins in lactating bovine mammary epithelial cells.

Cell Tissue Res 2021 Jan 12. Epub 2021 Jan 12.

Laboratory of Cell and Tissue Biology, Research Faculty of Agriculture, Hokkaido University, North 9, West 9, Sapporo, Hokkaido, 060-8589, Japan.

Mastitis causes a decrease in milk yield and abnormalities in milk components from dairy cows. Escherichia coli and the E. coli lipopolysaccharide (LPS) cell wall component directly downregulate milk production in bovine mammary epithelial cells (BMECs). However, the detailed mechanism by which this occurs in BMECs remains unclear. Various membrane proteins, such as immune sensors (Toll-like receptors, TLR), nutrient transporters (glucose transporter and aquaporin), and tight junction proteins (claudin and occludin) are involved in the onset of mastitis or milk production in BMECs. In this study, we investigated the influence of LPS on membrane proteins using an in vitro culture model. This mastitis model demonstrated a loss of glucose transporter-1 and aquaporin-3 at lateral membranes and a decrease in milk production in response to LPS treatment. LPS disrupted the tight junction barrier and caused compositional changes in localization of claudin-3 and claudin-4, although tight junctions were maintained to separate the apical membrane domains and the basolateral membrane domains. LPS did not significantly affect the expression level and subcellular localization of epidermal growth factor receptor in lactating BMECs with no detectable changes in MEK1/2-ERK1/2 signaling. In contrast, NFκB was concurrently activated with temporal translocation of TLR-4 in the apical membranes, whereas TLR-2 was not significantly influenced by LPS treatment. These findings indicate the importance of investigating the subcellular localization of membrane proteins to understand the molecular mechanism of LPS in milk production in mastitis.
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http://dx.doi.org/10.1007/s00441-020-03344-0DOI Listing
January 2021

Relationship between salivary alpha-amylase activity and pain relief scale score after low level laser therapy: a prospective interventional pilot study.

Lasers Med Sci 2021 Jan 7. Epub 2021 Jan 7.

Department of Anesthesiology, Nihon University School of Medicine, 1-6, Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-8309, Japan.

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http://dx.doi.org/10.1007/s10103-020-03217-6DOI Listing
January 2021

Anti-VEGF Therapy and Retinal Photocoagulation to Prevent Recurrence of Central Retinal Vein Occlusion: Two Case Reports of Young Patients.

Tokai J Exp Clin Med 2020 Dec 20;45(4):249-253. Epub 2020 Dec 20.

Department of Ophthalmology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.

Case 1: An 18-year-old man. On initial examination, he was diagnosed with central retinal vein occlusion (CRVO) due to optic papillitis. He had no previous systemic and ocular medical history. His best corrected visual acuity was 20/20 for the right eye, but macular edema accompanied by serous retinal detachment was observed about 2 months after the initial examination. Intravitreal anti-VEGF injection was performed, and the symptoms improved. Then, additional photocoagulation was applied to the retinal nonperfusion area, to maintain its normal state. Case 2: A 36-year-old man. He was diagnosed with neovascular glaucoma associated with CRVO in the right eye by his previous physician. Panretinal photocoagulation and intravitreal anti-VEGF injection were performed under maximum-tolerated medical therapy for the right eye. He had diabetes. On initial examination, his visual acuity was 20/100 and his intraocular pressure was 19mmHg. Macular edema and iris neovascularization recurred half a year later, so intravitreal anti-VEGF injection and additional photocoagulation were applied to nonperfusion area. After that, both macular edema and iris neovascularization have settled down. Conclusions: Intravitreal anti-VEGF injection is effective in young patients with CRVO. Also, photocoagulation to nonperfusion area in addition to the continuous treatment with intravitreal anti-VEGF injection seems effective for preventing recurrence.
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December 2020

Impaired Autophagy in Retinal Pigment Epithelial Cells Induced from iPS Cell of Distal Myopathy with Rimmed Vacuole Patient.

Tokai J Exp Clin Med 2020 Dec 20;45(4):243-248. Epub 2020 Dec 20.

Department of Ophthalmology, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.

Objective: We generated induced pluripotent stem (iPS) cells from a patient with distal myopathy with rimmed vacuoles (DMRV), in which sialic acids synthesis is reported to be defective. In this study, we examined whether the differentiation to retinal pigment epithelial (RPE) cells and autophagy was affected in the patient derived cells.

Methods: Patient derived iPS cells were established through the transduction of re-programming factors into peripheral mononuclear cells via retrovirus vectors. RPE cells were induced from iPS cells through aggregation culture. Then the autophagy induced by amino acid starvation was estimated by measuring LC3-containing "puncta" structure.

Results: A 3D aggregate culture of patient-derived iPS cells resulted in some irregular shapes, and the aggregate contained large vacuoles filled with lipid droplets and cellular components such as damaged mitochondria. RPE cells induced from patient-derived iPS cells showed impaired autophagy flux under amino acid starvation.

Conclusion: These findings were similar to those of sialidosis patient-derived iPS cells, in which cleavage of terminal sialic acids in oligosaccharide chains is defective. This suggests that the control of both the addition and removal of sialic acids are pivotal for autophagy progression.
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December 2020

Author Correction: Violet LED light enhances the recruitment of a thrip predator in open fields.

Sci Rep 2020 Dec 8;10(1):21822. Epub 2020 Dec 8.

Institute of Agrobiological Sciences, NARO, Ohwashi 1-2, Tsukuba, Ibaraki, 305-8634, Japan.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-78514-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722729PMC
December 2020

Metastatic Renal Cell Carcinoma to the Left Sphenoid Sinus: A Case Report in Light of the Literature.

Yonago Acta Med 2020 Nov 15;63(4):368-371. Epub 2020 Oct 15.

Division of Pathology, Tohoku Medical and Pharmaceutical University, Sendai 981-0905, Japan.

A 79-year-old Japanese woman presented with a rare case of metastatic renal cell carcinoma to the left sphenoid sinus with left nasal bleeding. She had previously had right radical nephrectomy for renal cell carcinoma at the age of 64 years and brain and spinal cord infarction at 74 years. Endoscopic examination revealed no mass in the nasal cavity. CT and MRI revealed a tumor in the left sphenoid sinus. The size of the tumor increased gradually from 12 to 15 years after the radical nephrectomy. Complete resection with endoscopic surgery was performed without preoperative embolization. The tumor cells had clear cytoplasm and were arranged in a trabecular pattern lined by a layer of endothelial cells. These findings were identical to the pathological findings of the surgical specimen of the renal cell carcinoma from 15 years previous. A pathological diagnosis of metastatic renal cell carcinoma of clear cell type (grade 1) was made. PET-CT demonstrated no metastasis. The patient's condition was successfully managed with excision of the tumor, and she remains well with no evidence of recurrence and metastasis 36 months after treatment. Metastatic renal cell carcinoma to the sphenoid sinus is rare, but it might be considered in the differential diagnosis of masses in the paranasal sinus even long after initial treatment of renal cancer.
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http://dx.doi.org/10.33160/yam.2020.11.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683906PMC
November 2020

Time-course microarray transcriptome data of cultured testes and age-matched testes.

Data Brief 2020 Dec 31;33:106482. Epub 2020 Oct 31.

Laboratory for Cellular Function Conversion Technology, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.

spermatogenesis, which produces fertile spermatozoa, has been successfully performed using an organ culture method from murine tissue. Here, we provide a dataset of time-course microarray transcriptome data of cultured neonate murine testes and age-matched -derived testes. The dataset presented here is related to the article titled "Transcriptome analysis reveals inadequate spermatogenesis and immediate radical immune reactions during organ culture in vitro spermatogenesis" published in Biochemical and Biophysical Research Communications in 2020 [1]. The raw data and pre-processed data are publicly available on the GEO repository (accession number GSE147982). Furthermore, the dataset provided here includes additional metadata, detailed explanations of the experiment, results of pre-processing, analysis scripts, and lists of differentially expressed genes from culture testes and testes at each time point.
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http://dx.doi.org/10.1016/j.dib.2020.106482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674299PMC
December 2020

The first evidence for SLFN11 expression as an independent prognostic factor for patients with esophageal cancer after chemoradiotherapy.

BMC Cancer 2020 Nov 20;20(1):1123. Epub 2020 Nov 20.

Center for Clinical Research, Hamamatsu University School of Medicine, Hamamatsu, Japan.

Background: Schlafen 11 (SLFN11) was recently identified as a dominant determinant of sensitivity to DNA-targeting agents including platinum-based drugs. SLFN11 also reportedly enhances cellular radiosensitivity. In this study, we examined the prognostic value of SLFN11 expression in esophageal squamous cell carcinoma (ESCC) patients treated with definitive chemoradiotherapy (dCRT), including the platinum derivative nedaplatin.

Methods: Seventy-three patients with ESCC who received dCRT were examined. SLFN11 expression was analyzed in pre-dCRT biopsies using immunohistochemistry and evaluated using a histo-score (H-score). Correlation between the H-score and overall survival was analyzed. An H-score ≥ 51 was provisionally defined as indicating high SLFN11 expression. Viability assays were performed using previously established isogenic human cell lines differentially expressing SLFN11 to test the usefulness of SLFN11 as marker of response to the dCRT regimen.

Results: High SLFN11 expression was independently associated with better prognosis in ESCC patients (hazard ratio = 0.295, 95% CI = 0.143-0.605, p = 0.001 for multivariate analysis). Kaplan-Meier survival curves showed that the prognostic value of high SLFN11 expression was most evident in patients at clinical stages II and III (p = 0.004). In in vitro study, SLFN11-proficient cells were highly sensitive to platinum derivatives compared to SLFN11-deficient cells.

Conclusion: SLFN11 expression is an independent prognostic factor for ESCC patients treated with dCRT and a potential biomarker for treatment selection of ESCC. Examination of SLFN11 may be particularly useful for clinical Stage II-III patients who wish to choose dCRT (instead of surgery) to preserve esophageal function.
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http://dx.doi.org/10.1186/s12885-020-07574-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678160PMC
November 2020

Menthol from Mentha piperita Suppresses the Milk Production of Lactating Mammary Epithelial Cells In Vivo and In Vitro.

Mol Nutr Food Res 2020 Nov 14:e2000853. Epub 2020 Nov 14.

Laboratory of Cell and Tissue Biology, Research Faculty of Agriculture, Hokkaido University, North 9, West 9, Sapporo, 060-8589, Japan.

Scope: Peppermint is traditionally used as an antigalactagogue in breastfeeding women. However, the suppressive mechanism remains unclear. The authors investigate whether and how peppermint influences milk production at the cellular and molecular levels.

Methods And Results: A lactating mammary epithelial cell (MEC) culture model that produces major milk components is prepared. Peppermint oil (PMO) suppresses β-casein production in conjunction with the induced enlargement of cytoplasmic lipid droplets (CLDs). PMO also significantly inactivates STAT5 and mTOR in the lactogenic signaling pathway. Menthol treatment, which is a primary PMO component, leads to decreases in β-casein production, enlarged CLDs, the inactivated STAT5 and mTOR. Eucalyptol and menthyl acetate, other components of peppermint, does not show suppressive effects on lactating MECs. The inactivation of STAT5 and mTOR upon menthol administration is also evident in alveolar MECs of lactating mice. Furthermore, lactating MECs expresses TRPM8 and TRPA1, which are menthol receptors known as cold receptors. Agonists of TRPM8 and TRPA1 suppresses β-casein production and inactivation of STAT5 and mTOR in the lactating MECs.

Conclusion: These findings indicate that peppermint has potential as an antigalactagogue. Menthol is suggested to be an active compound in peppermint. TRPM8 and TRPA1 may function as receptors for menthol.
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http://dx.doi.org/10.1002/mnfr.202000853DOI Listing
November 2020

[Treatment of transfusional iron overload].

Authors:
Takahiro Suzuki

Rinsho Ketsueki 2020 ;61(9):1205-1211

Department of Hematology, Kitasato University School of Medicine.

Frequent packed red blood cell (pRBC) transfusion can cause transfusional iron overload. Excess iron generates reactive oxygen species and provokes organ dysfunction. In lower-risk myelodysplastic syndrome (MDS), hyperferritinemia is known as one of the negative prognostic factors. Thus far, iron chelation therapy (ICT) is the only effective treatment for chronic iron overload induced by transfusion. Transfusional iron overload is diagnosed when serum ferritin (SF) levels are ≥500 ng/ml and cumulative volume of pRBC transfusion is ≥20 JPN units. ICT should be initiated when SF levels are ≥1,000 ng/ml and will be further continued until SF levels decline to <500 ng/ml. ICT serves to ameliorate organ dysfunction. A prospective study demonstrated that in patients with lower-risk MDS, ICT can reduce the risk of combined events, including cardiac events, hepatic events, AML transformation, and death of any cause. In some patients, hematological improvement will be observed. However, clinical features underling this hematological phenomenon are not fully understood. Therefore, ICT should not be performed solely for the purpose of hematological recovery.
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http://dx.doi.org/10.11406/rinketsu.61.1205DOI Listing
January 2021

Suppressive effects of curcumin on milk production without inflammatory responses in lactating mammary epithelial cells.

Phytomedicine 2021 Jan 1;80:153360. Epub 2020 Oct 1.

Laboratory of Cell and Tissue Biology, Research Faculty of Agriculture, Hokkaido University, North 9, West 9, 060-8589, Sapporo, Japan.

Background: Curcumin is a naturally occurring polyphenol found in Curcuma longa with multiple therapeutic properties, such as anti-inflammatory, wound healing and anti-cancer effects. Curcuma longa is also used as a galactagogue to improve milk production during lactation.

Purpose: To assess curcumin could have therapeutic potential for breastfeeding mothers, we investigated whether and how curcumin influences milk production in lactating mammary epithelial cells (MECs) at the cellular and molecular levels.

Methods: We prepared a lactating MEC culture model that produced milk components and formed less-permeable tight junctions (TJs) to investigate the molecular mechanism of curcumin on milk production, TJs, and inflammation in vitro.

Results: Curcumin downregulated milk production in lactation MECs concurrently with inactivation of lactogenesis-relating signaling (STAT5 and glucocorticoid receptor). The maintenance of a less-permeable TJ barrier was also confirmed, although the TJ protein claudin-4 increased. Curcumin inactivated NFκB and STAT3 signaling, which are closely involved in inflammatory responses in weaning and mastitis mammary glands. The expression levels of IL-1β and TNF-α were also decreased by curcumin treatment. Furthermore, curcumin blocked activation of inflammatory signaling by lipopolysaccharide treatment in MECs, similar to those in MECs that were treated with diclofenac sodium. The drastic phosphorylation of ERK was induced by curcumin treatment in the absence of EGF. U0126, an inhibitor of ERK phosphorylation, attenuated the adverse effects of curcumin on lactating MECs.

Conclusion: The results of the present study suggests that curcumin downregulates milk production via inactivation of STAT5 and GR signaling with concurrent suppression of inflammatory responses via STAT3 and NFκB signaling in MECs. These findings provide new insights into the role of curcumin as a mild suppressor of milk production without inflammatory damages in breastfeeding mothers.
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http://dx.doi.org/10.1016/j.phymed.2020.153360DOI Listing
January 2021

Role of CC chemokine receptor 9 in the progression of murine and human non-alcoholic steatohepatitis.

J Hepatol 2021 Mar 8;74(3):511-521. Epub 2020 Oct 8.

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. Electronic address:

Background & Aims: The number of patients with non-alcoholic steatohepatitis (NASH) is increasing globally. Recently, specific chemokine receptors have garnered interest as therapeutic targets in NASH. This is the first report to examine the role of the C-C chemokine receptor 9 (CCR9)/C-C chemokine receptor ligand 25 (CCL25) axis, and to reveal its therapeutic potential in NASH.

Methods: Patients with biopsy-proven non-alcoholic liver disease (NAFLD) were recruited and their serum and hepatic chemokine expression was examined. Furthermore, wild-type (WT) and Ccr9 mice were fed a high-fat high-cholesterol (HFHC) diet for 24 weeks to establish NASH.

Results: Serum CCL25, and hepatic CCR9 and CCL25 expression levels were increased in patients with NASH compared to healthy volunteers. Furthermore, Ccr9 mice were protected from HFHC diet-induced NASH progression both serologically and histologically. Flow cytometry and immunohistochemistry analysis showed that CCR9CD11b inflammatory macrophages accumulated in the inflamed livers of HFHC diet-fed mice, while the number was reduced in Ccr9 mice. Consistent with human NASH livers, CCR9 was also expressed on hepatic stellate cells (HSCs) in mice with NASH, while CCR9-deficient HSCs showed less fibrogenic potential in vitro. Administration of a CCR9 antagonist hampered further fibrosis progression in mice with NASH, supporting its potential clinical application. Finally, we showed that CCR9 blockade attenuated the development of NAFLD-related hepatocellular carcinoma in HF diet-fed mice injected with diethylnitrosamine.

Conclusions: These results highlight the role of the CCR9/CCL25 axis on macrophage recruitment and fibrosis formation in a murine NASH model, providing new insights into therapeutic strategies for NASH.

Lay Summary: Herein, we show that a specific chemokine axis involving a receptor (CCR9) and its ligand (CCL25) contributes to the progression of non-alcoholic steatohepatitis and carcinogenesis in humans and mice. Furthermore, treatment with a CCR9 antagonist ameliorates the development of steatohepatitis and holds promise for the treatment of patients with non-alcoholic steatohepatitis.
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http://dx.doi.org/10.1016/j.jhep.2020.09.033DOI Listing
March 2021

A Facelift Procedure for Resection of Benign Parapharyngeal Tumors.

Otolaryngol Pol 2020 Jun;74(5):1-5

Department of Otolaryngology, Head and Neck Surgery, Toho University Faculty of Medicine, Tokyo, Japan.

<b>Objective:</b> The feasibility, surgical outcomes and possible risks and complications encountered during a facelift procedure for patients with parapharyngeal space (PPS) tumor were analyzed. <br><b>Method:</b> This retrospective analysis examined 10 patients who underwent surgery for PPS tumor using a facelift incision at our institutes between April 2015 and August 2019. <br><b>Results:</b> This study included four retro-styloid (benign nerve sheath tumor) and six pre-styloid tumors (pleomorphic adenoma). Mean tumor dimensions were 4.1 x 4.2 x 3.8 cm respectively. None of the patients needed conversion to conventional open resection. Transient sensory changes in the auricle occurred in 30% of the patients; however, all recovered within four months. In all the patients, postoperative scars were fully concealed by the auricle and hair. No recurrences were detected during a mean follow-up period of 16.6 months. <br><b>Conclusion: </b>The facelift procedure provides adequate visualization, workspace and excellent cosmetic results in properly selected cases.
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http://dx.doi.org/10.5604/01.3001.0014.1614DOI Listing
June 2020

Distinct Expression Patterns of Fibrillar Collagen Types I, III, and V in Association with Mammary Gland Remodeling during Pregnancy, Lactation and Weaning.

J Mammary Gland Biol Neoplasia 2020 09 11;25(3):219-232. Epub 2020 Sep 11.

Laboratory of Cell and Tissue Biology, Research Faculty of Agriculture, Hokkaido University, North 9, West 9, Sapporo, 060-8589, Japan.

The mammary gland structurally and functionally remodels during pregnancy, during lactation and after weaning. There are three types of fibrillar collagens, types I, III, and V, in mammary stromal tissue. While the importance of the fibrillar structure of collagens for mammary morphogenesis has been suggested, the expression patterns of each type of fibrillar collagen in conjunction with mammary remodeling remain unclear. In this study, we investigated their expression patterns during pregnancy, parturition, lactation and involution. Type I collagen showed a well-developed fibril structure during pregnancy, but the fibrillar structure of type I collagen then became sparse at parturition and during lactation, which was concurrent with the downregulation of its mRNA and protein levels. The well-developed fibrillar structure of type I collagen reappeared after weaning. On the other hand, type V collagen showed a well-developed fibrillar structure and upregulation in the lactation period but not in the periods of pregnancy and involution. Type III collagen transiently developed a dense fibrillar network at the time of parturition and exhibited drastic increases in mRNA expression. These results indicate that each type of fibrillar collagen is distinctly involved in structural and functional remodeling in mammary glands during pregnancy, parturition, lactation, and involution after weaning. Furthermore, in vitro studies of mammary epithelial cells showed regulatory effects of type I collagen on cell adhesion, cell proliferation, ductal branching, and β-casein secretion. Each type of fibrillar collagen may have different roles in defining the cellular microenvironment in conjunction with structural and functional mammary gland remodeling.
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http://dx.doi.org/10.1007/s10911-020-09457-0DOI Listing
September 2020

AMBRA1 controls antigen-driven activation and proliferation of naïve T cells.

Int Immunol 2020 Sep 10. Epub 2020 Sep 10.

Department of Immunology, Tokai University School of Medicine, Isehara, Kanagawa, Japan.

AMBRA1 is a member of the BECN1 (BECLIN1) complex protein, and it plays a role in autophagy, cell death, tumorigenesis, and proliferation. We recently reported that on TCR stimulation, AMBRA1 controlled both autophagy and the cell cycle with metabolic regulation. Accumulating evidence has shown that autophagy and metabolic control are pivotal for T cell activation, clonal expansion, and effector/memory cell fate decision. However, it is unknown whether AMBRA1 is involved in T cell function under physiological conditions. We found that T cells in Ambra1-conditional knockout (cKO) mice induced exacerbated graft versus host response when they were transplanted into allogeneic BALB/c mice. Furthermore, Ambra1-deficient T cells showed increased proliferation and cytotoxic capability towards specific antigens in response to in vivo stimulation using allogeneic spleen cells. This enhanced immune response mainly contributed to naïve T cell hyperactivity. The T cell hyperactivity observed in this study were similar to those in some metabolic factor-deficient mice, but not those in other pro-autophagic factor-deficient mice. Under the static condition, however, naïve T cells were reduced in Ambra1-cKO mice, as same as in pro-autophagic factor-deficient mice. Collectively, these results suggested that AMBRA1 was involved in regulating T cell-mediated immune responses through autophagy-dependent and -independent mechanisms.
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http://dx.doi.org/10.1093/intimm/dxaa063DOI Listing
September 2020

[Acute leukemia developing in the second trimester of pregnancy].

Rinsho Ketsueki 2020 ;61(8):865-869

Department of Hematology, Kitasato University School of Medicine.

Acute leukemia (AL) during pregnancy poses a substantial risk to both mothers and fetuses. Treatment for leukemia should be initiated promptly; however, the management of AL in pregnant women and fetuses is usually challenging, especially during the second trimester. Here, we report two cases of AL that developed during the second trimester of pregnancy. In one case, chemotherapy was initiated while continuing the pregnancy; in the second case, a cesarean section was performed prior to chemotherapy initiation. As per current medical records, both infants are thriving without any medical problems. The optimal strategy for the treatment of AL during pregnancy typically includes chemotherapy after delivery. However, if fetal development is not sufficient for ex utero survival, the only alternatives available are the initiation of treatment while continuing the pregnancy or treatment after therapeutic abortion (if it is legally allowed). According to previous studies and as per the results from our first case, the initiation of chemotherapy while sustaining the pregnancy may be an acceptable option if it is conducted with appropriate informed consent. The treatment of AL in the second trimester of pregnancy should be carefully decided, while taking into account the medical, legal, and social aspects, such as gestational weeks, maternal and fetal status, and wishes of the patients and their families.
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http://dx.doi.org/10.11406/rinketsu.61.865DOI Listing
October 2020

Retained Products of Conception Fed by the Inferior Mesenteric Artery: A Case Report.

Tokai J Exp Clin Med 2020 Sep 20;45(3):131-135. Epub 2020 Sep 20.

Department of Clinical Genetics Tokai University Hospital, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.

Retained products of conception (RPOC) refer to the persistence of placental or fetal tissue in the uterus following delivery or miscarriage. RPOC may cause massive postpartum or post-abortion hemorrhage. Arterial embolization (AE) is an effective choice of management for postpartum hemorrhage including RPOC. We report a case of hemorrhagic RPOC, in which uterine artery embolization with transcervical resection did not achieve hemostasis, and laparotomy with uterine compression sutures was subsequently required. The RPOC was apparently fed by an aberrant branch derived from the inferior mesenteric artery (IMA). AE of IMA was not performed because of possible necrosis of the descending colon and rectum. A physician should be aware that AE is not an all-encompassing hemostatic technique for postpartum bleeding, such as with RPOC, and should keep alternatives in mind.
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September 2020

Comparing the efficacy and safety of Q-switched and picosecond lasers in the treatment of nevus of Ota: a systematic review and meta-analysis.

Lasers Med Sci 2020 Aug 24. Epub 2020 Aug 24.

Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, 1150 NW 14th Street, Miami, FL, 33136, USA.

Nevus of Ota is cosmetically burdensome and often prompts patients to seek treatment. Lasers are commonly used in removing these lesions; however, no systemic analysis has been conducted to support a gold standard laser. To conduct a meta-analysis of the efficacy and safety of Q-switched Nd:YAG lasers (QSNL), Q-switched ruby lasers (QSRL), Q-switched alexandrite lasers (QSAL), and picosecond alexandrite lasers (PSAL) in removing nevus of Ota. Inclusion criteria were nevus of Ota patients treated with QSNL, QSRL, QSAL, or PSAL and documentation of percent clearance and the rate of at least one adverse event. Articles in English, Chinese, or Japanese were included. The prespecified outcome measures were efficacy (percent clearance) and safety (rates of hyperpigmentation, hypopigmentation, scarring, and recurrence). The review included 57 studies and 13,417 patients. The pooled success rate was 64% for QSNL (95% CI 52-76%), 54% for QSRL (95% CI 39-69%), 58% for QSAL (95% CI 44-72%), and 100% for PSAL (95% CI 98-102%). The pooled adverse event rate was 5% for QSNL (95% CI 4-6%), 14% for QSRL (95% CI 9-19%), 9% for QSAL (95% CI 6-12%), and 44% (95% CI 31-57%) for PSAL. QSNL has the most evidence for effectively and safely treating nevus of Ota. PSAL potentially has a superior efficacy; however, further studies are needed to elucidate its side effect profile when treating nevus of Ota.
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http://dx.doi.org/10.1007/s10103-020-03125-9DOI Listing
August 2020