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1.  Nonunion of the First Sternocostal Synchondrosis Accompanied by Sternoclavicular Joint Synovitis 
Case Reports in Orthopedics  2014;2014:798329.
Injury to the sternocostal synchondrosis of the first rib is quite rare. We report one such case in a 50-year-old man with nonunion of the first sternocostal synchondrosis accompanied by synovitis of the sternoclavicular joint. He first underwent arthroscopic surgery of the left sternoclavicular joint. Postoperatively, the patient's symptoms decreased by half, but another pain and crepitus at the inferior lateral portion of the sternoclavicular joint developed. Since MRI and functional CT reexaminations revealed nonunion of the first sternocostal synchondrosis, resection arthroplasty of the first sternocostal joint was performed. This resulted in immediate resolution of the symptoms. At 2-year follow-up, his symptoms disappeared entirely with no limited range of motion of the shoulder.
PMCID: PMC4164510  PMID: 25254128
2.  Complete Genome Sequence of Ureaplasma parvum Serovar 3 Strain SV3F4, Isolated in Japan 
Genome Announcements  2014;2(3):e00256-14.
Here, we present the complete genome sequence of Ureaplasma parvum serovar 3, clinical strain SV3F4, isolated from a Japanese patient with a history of an infectious abortion.
PMCID: PMC4031331  PMID: 24855292
3.  Discoscopic Findings of High Signal Intensity Zones on Magnetic Resonance Imaging of Lumbar Intervertebral Discs 
Case Reports in Orthopedics  2014;2014:245952.
A 32-year-old man underwent radiofrequency thermal annuloplasty (TA) with percutaneous endoscopic discectomy (PED) under local anesthesia for chronic low back pain. His diagnosis was discogenic pain with a high signal intensity zone (HIZ) in the posterior corner of the L4-5 disc. Flexion pain was sporadic, and steroid injection was given twice for severe pain. After the third episode of strong pain, PED and TA were conducted. The discoscope was inserted into the posterior annulus and revealed a migrated white nucleus pulposus which was stained blue. Then, after moving the discoscope to the site of the HIZ, a migrated slightly red nucleus pulposus was found, suggesting inflammation and/or new vessels penetrating the mass. After removing the fragment, the HIZ site was ablated by TA. To our knowledge, this is the first report of the discoscopic findings of HIZ of the lumbar intervertebral disc.
PMCID: PMC4055382  PMID: 24963428
4.  Relevance of nuclear receptor expression in a Tchreg cell line, HOZOT: RXRα and PPARγ negatively regulate IFN-γ production 
Results in Immunology  2012;2:158-165.
Nuclear receptors (NRs) have recently received much attention for their newly discovered roles in T cell development, as exemplified by RARα (Treg cells) and RORγt (Th17 cells). In previous studies, we characterized a new type of T cell subset, designated as Tchreg (cytotoxic, helper, and regulatory T) cells, in terms of its cytokine signature. In this study, we investigated the expression and functional relevance of NRs in Tchreg cells by performing mRNA profiling of HOZOT, a cord blood-derived Tchreg cell line. We identified eleven inducible and eight constitutively expressed NRs in HOZOT. Among these NRs, RXRα and PPARγ showed features of signature NRs of Tchreg cells because they were selectively expressed in HOZOT compared with other T cell subsets. These NRs exhibited contrasting expression patterns, as RXRα was independent of anti-CD3/28 antibody stimulation while PPARγ was stimulated-dependent. Upon agonist treatment, both proteins translocated to the nucleus and inhibited IFN-γ production through binding to the promoter region of the IFN-γ gene. These results provide new insight into the roles of RXRα and PPARγ in T cell biology, especially in their biological relevance in Tchreg cells.
PMCID: PMC3862339  PMID: 24371580
5.  Alternative splicing produces structural and functional changes in CUGBP2 
BMC Biochemistry  2012;13:6.
CELF/Bruno-like proteins play multiple roles, including the regulation of alternative splicing and translation. These RNA-binding proteins contain two RNA recognition motif (RRM) domains at the N-terminus and another RRM at the C-terminus. CUGBP2 is a member of this family of proteins that possesses several alternatively spliced exons.
The present study investigated the expression of exon 14, which is an alternatively spliced exon and encodes the first half of the third RRM of CUGBP2. The ratio of exon 14 skipping product (R3δ) to its inclusion was reduced in neuronal cells induced from P19 cells and in the brain. Although full length CUGBP2 and the CUGBP2 R3δ isoforms showed a similar effect on the inclusion of the smooth muscle (SM) exon of the ACTN1 gene, these isoforms showed an opposite effect on the skipping of exon 11 in the insulin receptor gene. In addition, examination of structural changes in these isoforms by molecular dynamics simulation and NMR spectrometry suggested that the third RRM of R3δ isoform was flexible and did not form an RRM structure.
Our results suggest that CUGBP2 regulates the splicing of ACTN1 and insulin receptor by different mechanisms. Alternative splicing of CUGBP2 exon 14 contributes to the regulation of the splicing of the insulin receptor. The present findings specifically show how alternative splicing events that result in three-dimensional structural changes in CUGBP2 can lead to changes in its biological activity.
PMCID: PMC3368720  PMID: 22433174
6.  miR-155, a Modulator of FOXO3a Protein Expression, Is Underexpressed and Cannot Be Upregulated by Stimulation of HOZOT, a Line of Multifunctional Treg 
PLoS ONE  2011;6(2):e16841.
MicroRNAs (miRNAs) play important roles in regulating post-transcriptional gene repression in a variety of immunological processes. In particular, much attention has been focused on their roles in regulatory T (Treg) cells which are crucial for maintaining peripheral tolerance and controlling T cell responses. Recently, we established a novel type of human Treg cell line, termed HOZOT, multifunctional cells exhibiting a CD4+CD8+ phenotype. In this study, we performed miRNA profiling to identify signature miRNAs of HOZOT, and therein identified miR-155. Although miR-155 has also been characterized as a signature miRNA for FOXP3+ natural Treg (nTreg) cells, it was expressed quite differently in HOZOT cells. Under both stimulatory and non-stimulatory conditions, miR-155 expression remained at low levels in HOZOT, while its expression in nTreg and conventional T cells remarkably increased after stimulation. We next searched candidate target genes of miR-155 through bioinformatics, and identified FOXO3a, a negative regulator of Akt signaling, as a miR-155 target gene. Further studies by gain- and loss-of-function experiments supported a role for miR-155 in the regulation of FOXO3a protein expression in conventional T and HOZOT cells.
PMCID: PMC3033424  PMID: 21304824
7.  Spongipyran Synthetic Studies. Evolution of a Scalable Total Synthesis of (+)-Spongistatin 1 
Tetrahedron  2009;65(33):6489-6509.
Three syntheses of the architecturally complex, cytotoxic marine macrolide (+)-spongistatin 1 (1) are reported. Highlights of the first-generation synthesis include: use of a dithiane multicomponent linchpin coupling tactic for construction of the AB and CD spiroketals, and their union via a highly selective Evans boron-mediated aldol reaction en route to an ABCD aldehyde; introduction of the C(44)–C(51) side chain via a Lewis acid-mediated ring opening of a glucal epoxide with an allylstannane to assemble the EF subunit; and final fragment union via Wittig coupling of the ABCD and EF subunits to form the C(28)–C(29) olefin, followed by regioselective Yamaguchi macrolactonization and global deprotection. The second- and third- generation syntheses, designed with the goal of accessing one gram of (+)-spongistatin 1 (1), maintain both the first-generation strategy for the ABCD aldehyde and final fragment union, while incorporating two more efficient approaches for construction of the EF Wittig salt. The latter combine the original chelation-controlled dithiane union of the E- and F-ring progenitors with application of a highly efficient cyanohydrin alkylation to append the F-ring side chain, in conjunction with two independent tactics to access the F-ring pyran. The first F-ring synthesis showcases a Petasis-Ferrier union/rearrangement protocol to access tetrahydropyrans, permitting the preparation of 750 mgs of the EF Wittig salt, which in turn was converted to 80 mg of (+)-spongistatin 1, while the second F-ring strategy, incorporates an organocatalytic aldol reaction as the key construct, permitting completion of 1.009 g of totally synthetic (+)-spongistatin 1 (1). A brief analysis of the three syntheses alongside our earlier synthesis of (+)-spongistatin 2 is also presented.
PMCID: PMC2902791  PMID: 20640040

Results 1-7 (7)