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Author: Mizuki Watanabe (38)


Feb
2018

The AIM2 inflammasome is activated by DNA, leading to caspase-1 activation and release of pro-inflammatory cytokines interleukin 1β (IL-1β) and IL-18, which are critical mediators in host innate immune responses against various pathogens. Some viruses employ strategies to counteract inflammasome-mediated induction of pro-inflammatory cytokines, but their in vivo relevance is less well understood. Here we show that the herpes simplex virus 1 (HSV-1) tegument protein VP22 inhibits AIM2-dependent inflammasome activation.

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Sep
2017

VP26 is a herpes simplex virus 1 (HSV-1) small capsomere-interacting protein. In this study, we investigated the function of VP26 in HSV-1-infected cells with the following results. (i) The VP26 null mutation significantly impaired incorporation of minor capsid protein UL25 into nucleocapsids (type C capsids) in the nucleus.

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Jul
2017

A series of 8-substituted analogues of cyclic ADP-4-thioribose (cADPtR, 3), which is a stable equivalent of Ca-mobilizing second messenger cyclic ADP-ribose (cADPR, 1), were designed as potential pharmacological tools for studies on cADPR-modulated Casignaling pathways. These 8-amino analogue (8-NH-cADPtR, 4), 8-azido analogue (8-N-cADPtR, 5), and 8-chloro analogue (8-Cl-cADPtR, 6) were efficiently synthesized, where the stereoselective N1-β-thioribosyladenine ring closure reaction via an α/β-equilibrium of the 1-aminothioribose derivative and construction of the characteristic 18-membered pyrophosphate ring by Ag-promoted activation of a phenyl phosphorothioate type substrate were the two key steps. Although 8-NH-cADPR (2) is a well-known potent antagonist against cADPR-inducing Ca-release, the 4-thioribose congener 8-NH-cADPtR turned out unexpectedly to be a full agonist in sea urchin egg homogenate evaluation system.

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Jun
2017

prospective study OBJECTIVE:To evaluate repeatability of residual urine(RU)volume measurement(RUM)in patients with lumbar degenerative disorders.
RUM by abdominal echo is a non-invasive modality to evaluate lower urinary tract disorder(LUTD), repeatability of which is not found in urological disorders. Additionally, its repeatability has not been confirmed in spinal disorders.

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Feb
2017

Sterol regulatory element-binding proteins (SREBPs) are transcription factors that control lipid homeostasis. SREBP activation is regulated by a negative feedback loop in which sterols bind to SREBP cleavage-activating protein (SCAP), an escort protein essential for SREBP activation, or to insulin-induced genes (Insigs) (endoplasmic reticulum [ER] anchor proteins), sequestering the SREBP-SCAP-Insig complex in the ER. We screened a chemical library of endogenous molecules and identified 25-hydroxyvitamin D (25OHD) as an inhibitor of SREBP activation.

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Mar
2017

Detailed conformational analyses of our previously reported cyclopropane-based peptidomimetics and conformational analysis-driven ligand optimization are described. Computational calculations and X-ray crystallography showed that the characteristic features of cyclopropane function effectively to constrain the molecular conformation in a three-dimensionally diverse manner. Subsequent principal component analysis revealed that the diversity covers the broad chemical space filled by peptide secondary structures in terms of both main-chain and side-chain conformations.

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Dec
1969

A high-performance liquid chromatography with electrochemical detection (HPLC-ECD) system was developed for the simultaneous determination of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) in human plasma. In the present HPLC-ECD system, EPA, DHA, and AA were separated using a reverse-phase C30 column and detected based on the voltammetric reduction of 3,5-di-tert-butyl-1,2-benzoquinone (DBBQ). Chromatographic peak areas were proportional to the concentration of EPA, DHA, and AA from 0.

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Aug
2016

Cyclic adenosine diphosphate-carbocyclic-ribose (cADPcR, 2) is a stable equivalent of cyclic adenosine diphosphate-ribose (cADPR, 1), a Ca(2+)-mobilizing second messenger. On the basis of the structure-activity relationship of cADPR-related compounds and three-dimensional structural modeling of cADPcR, we designed and synthesized cyclic-ADP-4″α-azidoethyl carbocyclic-ribose (N3-cADPcR, 3) to demonstrate that it has a highly potent Ca(2+)-mobilizing activity (EC50 = 24 nM). N3-cADPcR will be a useful precursor for the preparation of biological tools effective to investigate cADPR-mediated signaling pathways.

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Aug
2016

Instrumented lumbar fusion can provide immediate stability and assist in satisfactory arthrodesis in patients who have pain or instability of the lumbar spine. Lumbar adjunctive fusion with decompression is often a good procedure for surgical management of degenerative spondylolisthesis (DS). Among various lumbar fusion techniques, lumbar interbody fusion (LIF) has an advantage in that it maintains favorable lumbar alignment and provides successful fusion with the added effect of indirect decompression.

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Dec
1969

The herpes simplex virus 1 (HSV-1) Us8A gene overlaps the gene that encodes glycoprotein E (gE). Previous studies have investigated the roles of Us8A in HSV-1 infection using null mutations in Us8A and gE; therefore, the role of Us8A remains to be elucidated. In this study, we investigated the function of Us8A and its phosphorylation at serine 61 (Ser-61), which we recently identified as a phosphorylation site by mass spectrometry-based phosphoproteomic analysis of HSV-1-infected cells, in HSV-1 pathogenesis.

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Jul
2015

Although intervertebral implants have been advocated for cervical fixation surgery, classic Cloward's method or Smith-Robinson's methods using autologous iliac bone has been performed in our clinic for about 30 years. In most cases, the postoperative clinical course is uneventful with satisfactory result. However, the authors experienced three cases of donor site iliac bone fracture in the patients who performed anterior cervical fixation surgery.

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Mar
2015

A 52-year-old female presented with stroke-like symptoms after high-dose methotrexate (HDMTX) therapy and MTX intrathecal injection (IT-MTX) as central nervous system (CNS) prophylaxis for intravascular large B-cell lymphoma (IVLBCL). She had been diagnosed as having IVLBCL without CNS involvement 5 months earlier and had received 6 courses of R-CHOP and 2 courses of HDMTX combined with IT-MTX. She experienced acute-onset right hemiparesis involving the face and arm, along with dysarthria, 7 days after the second HDMTX infusion.

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Feb
2015

Determination of subcellular localization and dynamics of mRNA is increasingly important to understanding gene expression. A new convenient and versatile method is reported that permits spatiotemporal imaging of specific non-engineered RNAs in living cells. The method uses transfection of a plasmid encoding a gene-specific RNA aptamer, combined with a cell-permeable synthetic small molecule, the fluorescence of which is restored only when the RNA aptamer hybridizes with its cognitive mRNA.

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Jan
2015

The mevalonate pathway is essential for the production of many important molecules in lipid biosynthesis. Inhibition of this pathway is the mechanism of statin cholesterol-lowering drugs, as well as the target of drugs to treat osteoporosis, to combat parasites, and to inhibit tumor cell growth. Unlike the human mevalonate pathway, the bacterial pathway appears to be regulated by diphosphomevalonate (DPM).

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Oct
2014

One of the major problems encountered in cell transplantation is the low level of survival of transplanted cells due to detachment-induced apoptosis, called anoikis. The present study reports on the chemical synthesis and biological evaluation of water-soluble molecules that protect suspended cells from anoikis. The synthetic molecules bind to and induce clusters of integrins and heparan-sulfate-bound syndecans, two classes of receptors that are important for extracellular matrix-mediated cell survival.

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Dec
1969

Transforaminal lumbar interbody fusion (TLIF) is widely accepted for the treatment of lumbar arthrodesis. However, the exact characteristics of TLIF depend on the number, location, shape, or materials of the interbody implants, and the type of posterior instrument. Clinical and biomechanical characteristics of each TLIF procedure are still unclear.

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Mar
2014

A systematic review of the English- and Japanese-language literature related to complications and reoperation rates of spinal surgery for degenerative lumbar disease was undertaken for articles published between 1993 and 2012. From these references, key articles were selected to determine the incidence of clinical perioperative and postoperative adverse events for different types of degenerative lumbar diseases. The mortality rate after lumbar degenerative spinal surgery was 0.

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Jan
2014

Patients with spinal degenerative diseases suffer not only neuropathy in the extremities but also lower urinary tract dysfunction(LUTD). Patients with cauda equina syndrome generally need emergency decompression to pelvic visceral function, especially that of the urinary bladder. However, less prominent voiding symptoms can be missed in clinical settings.

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Dec
2013

A preparative method for an optically active bromomethylenecyclopropane unit and its practical conversion to (Z)-cyclopropane-containing chiral compounds via Suzuki-Miyaura coupling were established.

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Dec
1969

We describe 5 cases of osteochondroma (OC) originating from lumbosacral spine which caused radiculopathy. Four cases originated from the lumbar spine; all from L4 inferior articular process and presented L5 radiculopathy, the other one case originated from the sacrum; the case from S1 superior articular process presented L5 radiculopathy. In all cases, definitive diagnosis was made with histopathological findings; typical cartilaginous capping was confirmed.

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Aug
2013

Hiccups are often observed in patients treated with cisplatin(CDDP)-based chemotherapy. It has been reported that gender and specific dosages of CDDP and antiemetic drugs(e.g.

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Apr
2013

Conformationally restricted peptidomimetics comprising eight stereoisomeric scaffolds with three-dimensional structural diversity were designed based on the structural features of cyclopropane, that is, cyclopropylic strain, which mimic wide-ranging tetrapeptide conformations covering β-turns through β-strands. Stereoselective synthesis of the designed peptidomimetics led to the identification of nonpeptidic melanocortin-4 receptor ligands.

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Oct
2012

In the clinical diagnosis of lumbosacral radicular symptoms, dermatome maps are commonly used, by which the segmental location of the affected nerve can be determined. However, the diagnosis is often difficult because the pattern of sensory disturbance does not necessarily match the patterns of classical dermatomes, and there are many dermatome maps made by different methods. The author examined the area of pain and numbness in cases of lumbosacral radiculopathy.

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Dec
1969

A 21-year-old woman presented with cervical myelopathy due to nontraumatic cervical disc herniation associated with cervical canal stenosis. The patient underwent removal of the herniated disc and anterior fusion with an autogenous iliac crest bone graft. After surgery, the patient showed satisfactory improvement.

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Oct
2012

Congerin is a proto-type galectin distributed on the skin and mucosal epithelia of the upper digestive tract of the Japanese conger eel Conger myriaster. It has at least 2 isotypes, namely, congerin I and II, and plays a role in bio-defense at the body surface. In the current study, we identified both isotypes in the peritoneal fluid and peritoneal cells of C.

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Sep
2012

Conger eel has two galectins, termed congerins I and II (Con I and II), that function in mucus as biodefense molecules. Con I and II have acquired a novel protein fold via domain swapping and a new ligand-binding site by accelerated evolution, which enables recognition of some marine bacteria. In this study, we identified a new congerin isotype, congerin P (Con-P), from the peritoneal cells of conger eel.

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Dec
1969

Marine bioresources produce a great variety of specific and potent bioactive molecules including natural organic compounds such as fatty acids, polysaccharides, polyether, peptides, proteins, and enzymes. Lectins are also one of the promising candidates for useful therapeutic agents because they can recognize the specific carbohydrate structures such as proteoglycans, glycoproteins, and glycolipids, resulting in the regulation of various cells via glycoconjugates and their physiological and pathological phenomenon through the host-pathogen interactions and cell-cell communications. Here, we review the multiple lectins from marine resources including fishes and sea invertebrate in terms of their structure-activity relationships and molecular evolution.

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Dec
1969

Transforaminal lumbar interbody fusion (TLIF) procedure is widely used, but the surgical indications for TLIF in elderly patients remain controversial because of potential risks such as inferior bone quality and higher rate of postoperative complications. Clinical efficacy and operative risk of TLIF in elderly patients are unclear. This study investigated the clinical effect and safety of TLIF for lumbar degenerative spondylolisthesis with radiculopathy or neurogenic claudication in patients aged 70 years or older.

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Dec
1969

A 39-year-old man presented with an extremely rare discal cyst at the L3-4 level manifesting as a left L4 radiculopathy. Two months after onset, he suffered right L4 radiculopathy with new lumbar disc protrusion. Five months after medical treatment, the patient's symptoms improved, and the discal cyst showed complete regression on magnetic resonance imaging.

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Jan
2012

The stereochemical diversity-oriented conformational restriction strategy can be an efficient method for developing specific ligands for drug target proteins. To develop potent histamine H(3) and/or H(4) receptor ligands, a series of conformationally restricted analogs of histamine with a chiral trans- or cis-4-amino-2,3-methano-1-(1H-imidazol-4-yl)butane structure was designed based on this strategy. These stereochemically diverse compounds were synthesized from previously developed versatile chiral cyclopropane units.

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Oct
2011

A series of optically active stereoisomers of 3,4-methanoarginine (1-4 and ent-1-ent-4) with trans/cis, D/L, and syn/anti stereochemical diversity, the side-chains of which were restricted in various special arrangements, was designed as biologically useful arginine mimetics. These conformationally restricted arginine analogues were synthesized effectively by using a series of chiral 3,4-methanoamino acid equivalents (7-10 and ent-7-ent-10) as the key synthetic units. Their biological evaluation with three isoforms of nitric oxide synthase showed that trans-3,4-methano-L-syn-arginine (2) was a good substrate, having close potency to L-arginine, and isoforms selectivities were also similar to those of l-arginine.

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Nov
2011

The authors report on an 81-year-old woman whose condition deteriorated 2 months after undergoing osteoplastic laminoplasty with placement of hydroxyapatite spacers. Magnetic resonance imaging showed postlaminectomy scar formation compressing the cervical spinal cord. The patient underwent laminectomy and removal of remarkably thick epidural scar tissue, which resulted in resolution of her symptoms.

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Aug
2011

Pseudolocalizing signs in lumbar spinal disease seems to be rarely encountered. To our knowledge, only six cases which caused L5 monoradiculopathy due to upper lumbar lesions have been described. We retrospectively reviewed patients with similar signs in our center, and we discussed the pathogenesis of such interesting neurological signs depending on our own and reported cases.

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May
2011

Ancestral structures of fish galectins (congerins) were determined. The extant isoforms I and II of congerin are the components of a fish biological defense system and have rapidly differentiated under natural selection pressure, by which congerin I has experienced a protein-fold evolution. The dimer structure of the ancestral congerin demonstrated intermediate features of the extant isoforms.

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Dec
2011

A case report.
The objective of this article was to report a case of bilateral lumbar discal cysts and discuss the clinical, radiological, and surgical findings.
Discal cysts are rare lesions and to our knowledge there has been no report on multiple discal cysts at one disc level.

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May
2010

We previously identified the highly potent histamine H(3) receptor antagonists (1R,2S)-2-[2-(4-chlorobenzylamino)ethyl]-1-(1H-imidazol-4-yl)cyclopropane (1) and its enantiomer ent-1. Although the conformations of 1 and ent-1 are restricted by the central cyclopropane ring, the 2-(4-chlorobenzylamino)ethyl side chain essential for the H(3) receptor binding may somewhat freely rotate. To investigate the bioactive conformation, the 1'-ethyl-substituted derivatives 2a and 2b and their enantiomers ent-2a and ent-2b were designed as side chain conformation-restricted analogues of 1 and ent-1, based on the cyclopropylic strain.

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Feb
2010

On the basis of the previous results on a histamine H(4) receptor agonist 4-methylhistamine and a cyclopropane-based conformationally restricted analog CEIC (3) with potent H(3)/H(4) receptor antagonistic effect, 4-methylhistamine analogs 4 and 5 of CEIC were designed and synthesized. Compound 4 showed strong affinity (K(i)=38.7 nM) for the H(3) receptor, which was more potent than a well-known H(3) antagonist thioperamide.

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Sep
2006

The stereochemical diversity-oriented conformational restriction strategy can be an efficient method for developing specific ligands for drug target proteins, especially in cases where neither the bioactive conformation nor the pharmacophore is known. To develop potent H3 and H4 receptor antagonists, a series of conformationally restricted analogues of histamine with a chiral cis- or trans-cyclopropane structure were designed on the basis of this strategy. These target compounds with stereochemical diversity were synthesized from the versatile chiral cyclopropane units (1S,2R)- and (1R,2R)-2-(tert-butyldiphenylsilyloxy)methyl-1-formylcyclopropane (6 and 7, respectively) or their enantiomers ent-6 and ent-7.

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