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Current progress and challenges in ocular surface reconstruction using cultivated epithelial sheet transplantation

Inatomi T, Nakamura T, Koizumi N, Sotozono C, Kinoshita S

Med J Malaysia, 2008 Jul;63 Suppl A:42.
PMID: 19024975

The cultivated epithelial transplantation is a new surgical modality for treating a variety of severe ocular surface disorders. This type of tissue-engineered epithelial sheet provides a rapid epithelial coverage on the corneal surface that reduces inflammation and postoperative complications. Although cultivated corneal epithelial transplantation is an effective surgical strategy, autologous transplantation is limited to unilateral cases. Autologous cultivated oral mucosal epithelial transplantation (COMET) enables surgeons to reconstruct the ocular surface using autologous, non-ocular surface cells, and has opened a new pathway for treating severe, bilateral ocular surface disorders.
Fulltext Inferior Healing Rate in Isolated Meniscal Repair than that in Meniscal Repair with Concomitant ACL Reconstruction Evaluated with MRI

Isono M, Koga H, Nakagawa Y, Nakamura T, Sekiya I, Katagiri H

Malays Orthop J, 2023 Mar;17(1):61-69.
PMID: 37064625 DOI: 10.5704/MOJ.2303.008

INTRODUCTION: Isolated meniscal repair has been suggested as one of the contributing factors in unhealed meniscal repair. The purpose of this study was to compare the healing rate between isolated meniscal repair and meniscal repair with concomitant anterior cruciate ligament reconstruction (ACLR) using a standardised assessment method after propensity score matching.
MATERIALS AND METHODS: Accuracy of the Crues' grading system for meniscal healing was validated using second-look arthroscopy as the reference standard in 17 patients. Propensity score matching (one-to-one) was performed between 26 patients who underwent isolated meniscal repair and 98 patients who underwent meniscal repair with concomitant ACLR. Patients were matched for sex, age, side and zone of the meniscal repair, and number of sutures. Healing rates at one year which were evaluated with magnetic resonance imaging (MRI) were compared between the two groups.
RESULTS: The sensitivity and specificity of the Crues' grading system on multiple plane MRI for meniscal healing were 100% and 83.3%, respectively. Both the isolated meniscal repair group and the meniscal repair with concomitant ACLR group included 21 patients after propensity score matching. Baseline characteristics did not differ significantly between the two groups. The healing rate was significantly lower in the isolated meniscal repairs group (14.3%) than in the meniscal repair concomitant with ACLR group (47.6%, P=0.04).
CONCLUSION: The healing rate for isolated meniscal repair using a standardised MRI assessment method was inferior to that of meniscal repair with concomitant ACLR after propensity score matching.
The mechanisms of fibroblast-mediated compaction of collagen gels and the mechanical niche around individual fibroblasts

Feng Z, Wagatsuma Y, Kikuchi M, Kosawada T, Nakamura T, Sato D, et al.

Biomaterials, 2014 Sep;35(28):8078-91.
PMID: 24976242 DOI: 10.1016/j.biomaterials.2014.05.072

Fibroblast-mediated compaction of collagen gels attracts extensive attention in studies of wound healing, cellular fate processes, and regenerative medicine. However, the underlying mechanism and the cellular mechanical niche still remain obscure. This study examines the mechanical behaviour of collagen fibrils during the process of compaction from an alternative perspective on the primary mechanical interaction, providing a new viewpoint on the behaviour of populated fibroblasts. We classify the collagen fibrils into three types - bent, stretched, and adherent - and deduce the respective equations governing the mechanical behaviour of each type; in particular, from a putative principle based on the stationary state of the instantaneous Hamiltonian of the mechanotransduction system, we originally quantify the stretching force exerted on each stretched fibrils. Via careful verification of a structural elementary model based on this classification, we demonstrate a clear physical picture of the compaction process, quantitatively elucidate the panorama of the micro mechanical niche and reveal an intrinsic biphasic relationship between cellular traction force and matrix elasticity. Our results also infer the underlying mechanism of tensional homoeostasis and stress shielding of fibroblasts. With this study, and sequel investigations on the putative principle proposed herein, we anticipate a refocus of the research on cellular mechanobiology, in vitro and in vivo.
Apigenin di- and trirhamnoside from Asplenium normale in Malaysia

Iwashina T, Matsumoto S, Kitajima J, Nakamura T, Kokubugata G, Suleiman M, et al.

Nat Prod Commun, 2010 Jan;5(1):39-42.
PMID: 20184017

Two new flavone rhamnosides, apigenin 7-O-alpha-L-rhamnopyranosyl-(1-->4)-O-alpha-L-rhamnopyranoside and apigenin 7-O-alpha-L-rhamnopyranosyl-(1-->4)-O-alpha-L-rhamnopyranoside-4'-O-alpha-L-rhamnopyranoside were isolated from the fronds of Asplenium normale D. Don, together with two known C-glycosylflavones, vicenin-2 and lucenin-2. The chemical structures of the isolated glycosides were established by UV, LC-MS, characterization of acid hydrolysates, and 1H and 13C NMR spectroscopy.
A fibril-based structural constitutive theory reveals the dominant role of network characteristics on the mechanical behavior of fibroblast-compacted collagen gels

Feng Z, Ishiguro Y, Fujita K, Kosawada T, Nakamura T, Sato D, et al.

Biomaterials, 2015 Oct;67:365-81.
PMID: 26247391 DOI: 10.1016/j.biomaterials.2015.07.038

In this paper, we present a general, fibril-based structural constitutive theory which accounts for three material aspects of crosslinked filamentous materials: the single fibrillar force response, the fibrillar network model, and the effects of alterations to the fibrillar network. In the case of the single fibrillar response, we develop a formula that covers the entropic and enthalpic deformation regions, and introduce the relaxation phase to explain the observed force decay after crosslink breakage. For the filamentous network model, we characterize the constituent element of the fibrillar network in terms its end-to-end distance vector and its contour length, then decompose the vector orientation into an isotropic random term and a specific alignment, paving the way for an expanded formalism from principal deformation to general 3D deformation; and, more important, we define a critical core quantity over which macroscale mechanical characteristics can be integrated: the ratio of the initial end-to-end distance to the contour length (and its probability function). For network alterations, we quantitatively treat changes in constituent elements and relate these changes to the alteration of network characteristics. Singular in its physical rigor and clarity, this constitutive theory can reproduce and predict a wide range of nonlinear mechanical behavior in materials composed of a crosslinked filamentous network, including: stress relaxation (with dual relaxation coefficients as typically observed in soft tissues); hysteresis with decreasing maximum stress under serial cyclic loading; strain-stiffening under uniaxial tension; the rupture point of the structure as a whole; various effects of biaxial tensile loading; strain-stiffening under simple shearing; the so-called "negative normal stress" phenomenon; and enthalpic elastic behaviors of the constituent element. Applied to compacted collagen gels, the theory demonstrates that collagen fibrils behave as enthalpic elasticas with linear elasticity within the gels, and that the macroscale nonlinearity of the gels originates from the curved fibrillar network. Meanwhile, the underlying factors that determine the mechanical properties of the gels are clarified. Finally, the implications of this study on the enhancement of the mechanical properties of compacted collagen gels and on the cellular mechanics with this model tissue are discussed.
A novel sponge-derived protein thrombocorticin is a new agonist for thrombopoietin receptor

Watari H, Nakajima H, Atsuumi W, Nakamura T, Nanya T, Ise Y, et al.

Comp Biochem Physiol C Toxicol Pharmacol, 2019 Jul;221:82-88.
PMID: 30978513 DOI: 10.1016/j.cbpc.2019.04.003

We screened 868 marine extracts in search of hematopoietic molecules resulted in findings of several extracts that proliferated Ba/F3-HuMpl cells but not the cells expressed with other hematopoietic cytokine receptors, EPO and G-CSF. Separation of the most potent extract of a Micronesian sponge Corticium sp., guided by the cell proliferation assay using Ba/F3-HuMpl cells resulted in an isolation of thrombocorticin (ThC), a novel 14 kDa protein as an active principal. ThC displayed concentration-dependent proliferation of Ba/F3-HuMpl cells, and had a stronger activity than that of eltrombopag, a small molecule drug used to treat thrombocytopenia. ThC induced phosphorylation of STAT5, suggesting that it activates Jak/STAT pathway as in the case of TPO. These results together indicated that ThC is a specific agonist for c-Mpl, although the size and shape differs largely from TPO. Here we present isolation, characterization and biological activity of ThC.
A new peptaibol, RK-026A, from the soil fungus Trichoderma sp. RK10-F026 by culture condition-dependent screening

Rawa MSA, Nogawa T, Okano A, Futamura Y, Nakamura T, Wahab HA, et al.

Biosci Biotechnol Biochem, 2021 Jan 07;85(1):69-76.
PMID: 33577647 DOI: 10.1093/bbb/zbaa051

A new peptaibol, RK-026A (1) was isolated from a fungus, Trichoderma sp. RK10-F026, along with atroviridin B (2), alamethicin II (3), and polysporin B (4) as a cytotoxic compound, which was selected by principal component analysis of the MS data from 5 different culture conditions. The structure of 1 was determined as a new atroviridin B derivative containing Glu at the 18th residue instead of Gln by NMR and HR-MS analyses including the investigation of detailed MS/MS fragmentations. 1 showed cytotoxicity toward K562 leukemia cells at an IC50 value of 4.1 µm.
RK-1355A and B, novel quinomycin derivatives isolated from a microbial metabolites fraction library based on NPPlot screening

Lim CL, Nogawa T, Uramoto M, Okano A, Hongo Y, Nakamura T, et al.

J Antibiot (Tokyo), 2014 Apr;67(4):323-9.
PMID: 24496142 DOI: 10.1038/ja.2013.144

Two novel quinomycin derivatives, RK-1355A (1) and B (2), and one known quinomycin derivative, UK-63,598 (3), were isolated from a microbial metabolites fraction library of Streptomyces sp. RK88-1355 based on Natural Products Plot screening. The structural elucidation of 1 and 2 was established through two-dimensional NMR and mass spectrometric measurements. They belong to a class of quinomycin antibiotics family having 3-hydroxyquinaldic acid and a sulfoxide moiety. They are the first examples for natural products as a quinoline type quinomycin having a sulfoxide on the intramolecular cross-linkage. They showed potent antiproliferative activities against various cancer cell lines and they were also found to exhibit moderate antibacterial activity.
Fiber-specific white matter analysis reflects upper motor neuron impairment in amyotrophic lateral sclerosis

Ogura A, Kawabata K, Watanabe H, Choy SW, Bagarinao E, Kato T, et al.

Eur J Neurol, 2022 Feb;29(2):432-440.
PMID: 34632672 DOI: 10.1111/ene.15136

BACKGROUND AND PURPOSE: To clarify the relationship between fiber-specific white matter changes in amyotrophic lateral sclerosis (ALS) and clinical signs of upper motor neuron (UMN) involvement, we performed a fixel-based analysis (FBA), a novel framework for diffusion-weighted imaging analysis.
METHODS: We enrolled 96 participants, including 48 nonfamilial ALS patients and 48 age- and sex-matched healthy controls (HCs), in this study and conducted whole-brain FBA and voxel-based morphometry analysis. We compared the fiber density (FD), fiber morphology (fiber cross-section [FC]), and a combined index of FD and FC (FDC) between the ALS and HC groups. We performed a tract-of-interest analysis to extract FD values across the significant regions in the whole-brain analysis. Then, we evaluated the associations between FD values and clinical variables.
RESULTS: The bilateral corticospinal tracts (CSTs) and the corpus callosum (CC) showed reduced FD and FDC in ALS patients compared with HCs (p
Fulltext Report on the international Primary Neurosurgical Life Support course in the eighth Asian Congress of Neurological Surgeons in Kuala Lumpur, Malaysia

Nakamura T, Ajimi Y, Okudera H, Yamada M, Toyoda I, Itoh K, et al.

Asian J Neurosurg, 2011 Jan;6(1):2-5.
PMID: 22059097 DOI: 10.4103/1793-5482.85625

On November 22, 2010, a simulation-based hands-on education course for medical staff in the neurosurgical fields was held in 8(th) Asian Congress of Neurological Surgeons (ACNS) in Kuala Lumpur, Malaysia. The present education course called Primary Neurosurgical Life Support (PNLS) course had been started by the Japan Society of Neurosurgical Emergency since 2008. This report summarizes the international version of PNLS course in 8(th) ACNS.