Publications by authors named "Kozo Yoneda"

92 Publications

Symmetrical Skin Lesions on the Gluteal Region in a Patient with Anti-Laminin-332 Mucous Membrane Pemphigoid.

Acta Dermatovenerol Croat 2021 Jul;29(2):105-107

Nobuki Maki; MD, Department of Dermatology Akita National Hospital, 84-40 Idonosawa, Iwakiuchimichikawa, Yurihonjo, Akita 018-1393 Japan;

Mucous membrane pemphigoid (MMP), previously called cicatricial pemphigoid, is a rare subepidermal immunobullous disorder that primarily affects the mucous membranes (1,2). MMP is divided into two major subtypes, anti-BP180-type MMP and anti-laminin-332 (previously called laminin 5 or epiligrin) MMP. Anti-laminin-332 MMP is known to be associated with malignant tumors (3), which may cause overexpression of autoantibodies and induce autoimmunity to laminin-332 (4). MMP primarily affects the mucous membranes, and widespread skin lesions are rare. In MMP, circumscribed skin lesions have been previously reported as occurring on the head, neck, and upper trunk (5). We report a case of anti-laminin-332 MMP presenting with symmetrical skin lesions characteristic of MMP on the weight-bearing areas of the gluteal region. A 66-year-old Japanese man presented with a month-long history of multiple erosions and blisters on the mucous membranes and skin, with conjunctival hyperemia, nasal obstruction, oral pain, and hoarseness of voice. Three days before the first visit, he was diagnosed with gastric cancer with liver metastasis by gastrointestinal endoscopy and abdominal ultrasound examination for tarry stool. Physical examination demonstrated erosions and tense bullae on the conjunctivae, tongue, and lips (Figure 1, a,b), as well as erosive erythematous skin lesions on the nape, right index finger, both legs, and symmetric lesions on the gluteal region (Figure 1, c). His body weight was 86 kg. Laboratory examinations showed slight liver dysfunction and elevation of C-reactive protein levels. Histopathologic examination of the skin lesions demonstrated subepidermal blisters with lymphocytic and eosinophilic infiltrates (Figure 1, d,e). Direct immunofluorescence (IF) revealed linear deposits of IgG and C3, but not IgA, along the basement membrane zone (BMZ) (Figure 1, f,g). An IgG subclass study showed IgG1 and IgG4 deposits. Indirect IF on normal human skin revealed weak positivity for IgA anti-keratinocyte cell surface antibodies and IgG anti-BMZ antibodies, which were bound to the dermal side of 1 mol/L NaCl-split skin (Figure 1, h). IgG immunoblot analyses of both normal human epidermal and dermal extracts showed negative results (including BP230, BP180, 290 kDa type VII collagen, and 200 kDa laminin-γ1). Immunoprecipitation using radio-labeled cultured keratinocyte lysate demonstrated positive reactivity with laminin-332 (Figure 1, i). We established the diagnosis of anti-laminin-332 MMP. We started treatment with oral minocycline (200 mg/day) and niacinamide (900 mg/day) with topical corticosteroids without any effect after 2 weeks of therapy. Administration of oral prednisolone (40 mg/day) with topical corticosteroids and alprostadil ointment on the skin lesions, as well as beclometasone dipropionate powder on the oral lesions resulted in significant improvement of mucocutaneous lesions within 10 days. Although the gastric cancer and liver metastasis initially responded to chemotherapy with fluorouracil and cisplatin, the patient succumbed to multiple organ failure 9 months after the initial visit. Anti-laminin-332 antibodies were originally detected by immunoprecipitation, as in our case. Immunoblotting of purified human laminin-332 have been subsequently developed, which detects the 165/145 kDa α3, 140 kDa β3, and 105 kDa γ2 subunits of laminin-332 in various patterns (6). Today, the ELISA system uses laminin-332 preparations as adjunct diagnostic tools in MMP (7). Occasionally, a wide spectrum of autoantibodies is detected in MMP, for example, MMP with IgG antibodies to both BP180 and laminin-332, which were considered to be developed via epitope spreading. Detection of circulating IgA autoantibodies against the skin have also been reported in MMP (8). However, the pathogenic significance and mechanisms of coexistence of IgG anti-laminin-332 antibodies and IgA anti-keratinocyte cell surface antibodies found in our case are currently unknown. It is generally considered that IgG1 antibodies activate complements and are pathogenic in MMP, while IgG4 antibodies behave as blocking antibodies and are protective. In our case, direct IF revealed IgG1 and IgG4 deposits; the same was reported in a previous case report (9). The pathogenic roles of autoantibodies with different IgG subclasses need to be analyzed in further studies. Conjunctival mucosal lesions in MMP may occur by rubbing of the eyes due to irritation. Blinking subjects the conjunctivae to repeated friction. Vocal cords vibrate during breathing and speaking. The tongue moves while eating and drinking; in particular, the tip of the tongue gets into frequent contact with the inner sides of the incisor teeth. In the present case, characteristic symmetrical skin lesions were seen on the weight-bearing areas of the gluteal region on bony prominences which receive mechanical stresses in the sitting position. These skin lesions were subjected to repeated stretch and pressure stresses, but no ischemic changes were observed, such as decubitus ulcers. Therefore, the symmetrical skin lesions in the gluteal region as well as the ocular and oral mucosal lesions seen in our patient might have resulted from the same mechanism of pathogenesis. We reported a case of anti-laminin-332 MMP presenting with symmetrical gluteal skin lesions, probably induced by mechanical stress. MMP primarily affects the mucous membranes, and widespread skin lesions are rare. Our case emphasizes that clinicians need to specifically check for the presence of skin lesions on weight-bearing parts of the body during examination of patients with suspected MMP.
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July 2021

Sign of Leser-Trélat Associated with Waldenström's Macroglobulinemia.

Indian J Dermatol 2021 Mar-Apr;66(2):225

Department of Dermatology, Faculty of Medicine, Kagawa University, Kagawa, Japan.

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http://dx.doi.org/10.4103/ijd.IJD_556_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208244PMC
June 2021

Japanese guidelines for the management of palmoplantar keratoderma.

J Dermatol 2021 Aug 13;48(8):e353-e367. Epub 2021 Jun 13.

Department of Dermatology, Osaka City University Graduate School of Medicine, Osaka, Japan.

Palmoplantar keratoderma (PPK) is a collective term for keratinizing disorders in which the main clinical symptom is hyperkeratosis on the palms and soles. To establish the first Japanese guidelines approved by the Japanese Dermatological Association for the management of PPKs, the Committee for the Management of PPKs was founded as part of the Study Group for Rare Intractable Diseases. These guidelines aim to provide current information for the management of PPKs in Japan. Based on evidence, they summarize the clinical manifestations, pathophysiologies, diagnostic criteria, disease severity determination criteria, treatment, and treatment recommendations. Because of the rarity of PPKs, there are only few clinical studies with a high degree of evidence. Therefore, several parts of these guidelines were established based on the opinions of the committee. To further optimize the guidelines, periodic revision in line with new evidence is necessary.
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http://dx.doi.org/10.1111/1346-8138.15850DOI Listing
August 2021

Inhibition of α-adrenoceptor is renoprotective in 5/6 nephrectomy-induced chronic kidney injury rats.

J Pharmacol Sci 2021 Jan 17;145(1):79-87. Epub 2020 Nov 17.

Laboratory of Clinical Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiori-kita, Tondabayashi, Osaka, 584-8540, Japan. Electronic address:

In the present study, we investigated the renoprotective effects of long-term treatment with yohimbine, an α-adrenoceptor inhibitor, in a 5/6 nephrectomy-induced chronic kidney disease (CKD) rat model. Male Sprague-Dawley rats were randomly allocated into the following groups: sham-operated, 5/6-nephrectomized (5/6 Nx), 5/6 Nx + low or high dose of yohimbine (0.3 or 3.0 mg/L in drinking water, respectively), and 5/6 Nx + hydralazine (250 mg/L in drinking water). The 5/6 Nx group presented with renal dysfunction, hypertension, noradrenaline overproduction, and histopathological injuries. Blood pressure decreased in both the yohimbine- and hydralazine-treated groups. Treatment with high dose of yohimbine, but not hydralazine, apparently attenuated urinary protein excretion and noradrenaline concentration of renal venous plasma. Renal fibrosis and upregulated fibrosis-related gene expression were suppressed by high dose of yohimbine. Furthermore, yohimbine, but not hydralazine, treatment ameliorated the urinary concentration ability. These findings suggest that long-term yohimbine treatment can be a useful therapeutic option to prevent the progression of CKD.
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http://dx.doi.org/10.1016/j.jphs.2020.11.001DOI Listing
January 2021

Clinical practice guide for the treatment of perforating dermatosis.

J Dermatol 2020 Dec 23;47(12):1374-1382. Epub 2020 Oct 23.

Department of Dermatology, Juntendo University Urayasu Hospital, Urayasu, Japan.

Perforating dermatoses are a heterogeneous skin disease group defined by transepidermal elimination of various skin materials. Four classical forms of primary perforating dermatosis have been described, where the transepidermal elimination mechanism represents the hallmark of the disease: acquired reactive perforating collagenosis, elastosis perforans serpiginosa, Kyrle's disease and perforating folliculitis. Acquired reactive perforating collagenosis presents with transepidermal elimination of collagen fibers. Elastosis perforans serpiginosum presents with the elimination of elastic fibers. Kyrle's disease presents with transepidermal elimination of abnormal keratin. In perforating folliculitis, it is the content of the follicle. We established diagnostic criteria and severity classification. In addition, the Japanese guideline for treatment of perforating dermatoses was updated using the Medical Information Network Distribution Service (MINDS) methodology. The guideline is based on a systematic published work review completed from 1989 to 2019, and on a formal consensus and approval process. Most medical published work on the treatment is limited to individual case reports and small series of patients. The guideline covers treatment options considered relevant by the expert panel and approved in Japan at the time of the consensus conference.
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http://dx.doi.org/10.1111/1346-8138.15647DOI Listing
December 2020

N,N-Dimethylaminopyrene as a fluorescent affinity mass tag for ligand-binding mode analysis.

Sci Rep 2020 04 30;10(1):7311. Epub 2020 Apr 30.

Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa, Nagoya, 464-8601, Japan.

Elucidation of the binding mode of protein-ligand interactions provides insights for the design of new pharmacological tools and drug leads. Specific labeling of target proteins with chemical probes, in which the ligands are conjugated with reacting and detecting groups, can establish the binding positions of ligands. Label-assisted laser desorption/ionization mass spectrometry (LA-LDI MS) is a promising detection method to selectively detect labeled molecules. However, previous LDI MS tags, such as nitrogen-substituted pyrenes, had problems with low sensitivity and stability. Here we show 6-N,N-dimethylaminopyrene (dmpy) as a versatile mass tag, which was detected at an amount of 0.1 fmol by LA-LDI MS and applicable for MS/MS analysis. By using ligand-dissociation-type dmpy probes and affinity purification with a polystyrene gel, we demonstrated that dmpy-labeled peptides were predominantly detected by MALDI MS. Our dmpy-probe-labeling method might be highly useful for determining the target biomacromolecules of various ligands and their binding sites.
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http://dx.doi.org/10.1038/s41598-020-64321-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192892PMC
April 2020

Yohimbine ameliorates lipopolysaccharide-induced acute kidney injury in rats.

Eur J Pharmacol 2020 Mar 11;871:172917. Epub 2020 Jan 11.

Department of Pharmacology, Osaka City University Graduate School of Medicine, Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.

Sepsis-induced acute kidney injury (AKI) is frequently observed in the intensive care unit. We previously revealed that yohimbine, an α-adrenoceptor antagonist, has protective effects on renal ischemia/reperfusion injury-induced AKI in rats. This study aimed to investigate the renoprotective effect of yohimbine on lipopolysaccharide (LPS)-induced AKI in rats. Male Sprague Dawley rats were randomly divided into the following groups: Sham-operated group, LPS (10 mg/kg, i.p.) and LPS + yohimbine (0.1 or 0.5 mg/kg, i.p.). Kidney functional parameters of blood urea nitrogen (BUN) and plasma creatinine (Pcr) were aggravated in the LPS group. Administration of LPS decreased blood pressure. In addition, kidney injury molecule-1, inducible nitric oxide synthase (iNOS) and expression of various cytokines such as tumour necrosis factor-α, monocyte chemoattractant protein-1, and interleukin (IL)-6 were increased by LPS administration. Yohimbine treatment clearly ameliorated the damaged kidney function and low blood pressure due to LPS. Moreover, yohimbine suppressed cytokine mRNA and iNOS expression enhanced by LPS. However, anti-inflammatory cytokine IL-10 mRNA levels were augmented by yohimbine. Nuclear localization of nuclear factor-kappa B (NF-κB) in the kidney was observed 1 h after injection of LPS in rats. Yohimbine blocked the nuclear localization of NF-κB. In addition, phosphorylation of extracellular signal-regulated kinase (ERK) and cAMP response element binding protein (CREB) were enhanced with yohimbine. These results suggest that yohimbine can prevent LPS-induced sepsis associated with kidney injury by suppressing inflammatory cytokine and iNOS expression as well as enhancing IL-10 expression via ERK/CREB phosphorylation.
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http://dx.doi.org/10.1016/j.ejphar.2020.172917DOI Listing
March 2020

Post-treatment with JP-1302 protects against renal ischemia/reperfusion-induced acute kidney injury in rats.

J Pharmacol Sci 2019 Mar 31;139(3):137-142. Epub 2018 Dec 31.

Laboratory of Clinical Pharmacology, Faculty of Pharmacy, Osaka Ohtani University, 3-11-1 Nishikiori-kita, Tondabayashi, Osaka, 584-8540, Japan.

Ischemia/reperfusion injury is the most common cause of acute kidney injury. We previously revealed that pre-treatment with yohimbine or JP-1302 attenuated renal ischemia/reperfusion injury by inhibition of α2C-adrenoceptor antagonist. The aim of the present study is to investigate the effects of post-treatment with JP-1302 on renal ischemia/reperfusion injury in rats. Male Sprague Dawley rats were randomly divided into four groups: sham operation, ischemia/reperfusion, pre-treatment with JP-1302 (3.0 mg/kg) and post-treatment with JP-1302 groups. In ischemia/reperfusion injury, renal functional parameters, such as blood urea nitrogen, plasma creatinine and creatinine clearance, deteriorated after reperfusion. Renal venous norepinephrine concentrations, as well as inflammatory molecules in the kidney increased after reperfusion. Both pre- and post-treatment with JP-1302 improved renal dysfunction, tissue damage, renal venous norepinephrine concentrations and inflammatory molecules expression in the kidney. In conclusion, these results suggest that post-treatment with JP-1302 protects on ischemia/reperfusion-induced acute kidney injury by suppressing cytokine upregulation via α2C-adrenoceptors.
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http://dx.doi.org/10.1016/j.jphs.2018.12.008DOI Listing
March 2019

Specific protein-labeling and ligand-binding position analysis with amidopyrene probes as LDI MS tags.

Org Biomol Chem 2018 10;16(42):7883-7890

Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8571, Japan.

To readily analyze the binding mode of protein-ligand interactions, we developed ligand-bound-type and ligand-dissociation-type probes having 6-amidopyrene (apy) as a detecting group. Matrix- and label-assisted laser desorption/ionization mass spectrometry (MALDI and LA-LDI MS) analyses and a covalent docking simulation using these probes precisely determined the binding position of the ligand biotin on the target protein avidin (RMSD = 0.786 and 0.332 Å). Our apy-probe-labeling method may be useful for determining the unknown ligand-binding sites of various target proteins.
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http://dx.doi.org/10.1039/c8ob02222dDOI Listing
October 2018

Localized nodular pemphigoid.

Int J Dermatol 2018 May 10;57(5):587-589. Epub 2018 Jan 10.

Department of Dermatology, Faculty of Medicine, Osaka City University, Osaka, Japan.

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http://dx.doi.org/10.1111/ijd.13889DOI Listing
May 2018

IL-17A induces heterogeneous macrophages, and it does not alter the effects of lipopolysaccharides on macrophage activation in the skin of mice.

Sci Rep 2017 09 29;7(1):12473. Epub 2017 Sep 29.

Department of Dermatology, Kagawa University, Kagawa, Japan.

Macrophages are central to inflammatory response and become polarized towards the M1 or M2 states upon activation by immunostimulants. In this study, we investigated the effects of lipopolysaccharides (LPS) and interleukin (IL)-17A on the activation of macrophages in in vivo mouse skin. We examined whether macrophages are activated in the skin of imiquimod (IMQ)-treated mice, a model for IL-17A-induced psoriasis-like skin inflammation, and flaky-tail (Flg ) mice, a model for IL-17A-induced chronic atopic dermatitis-like skin inflammation. LPS and IL-17A independently increased the expression levels of iNOS, CX3CR1, CD206, phospho-STAT1 and phospho-STAT3 proteins in the skin of B6 mice, and the effects of LPS was not altered by IL-17A. The expression levels of these proteins were increased in the skin of IMQ-treated and Flg mice. IL-17A neutralization increased the expressions of iNOS and phospho-STAT1 in the IMQ-treated skin, but it decreased the expressions of CD206 and phospho-STAT3 proteins in the skin of Flg mice, suggesting that macrophages to change from the M2 to the M1 state in the skin of these mice. These results suggest that IL-17A is involved in the activation of macrophages that are in the process of adopting the heterogeneous profiles of both the M1 and M2 states.
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http://dx.doi.org/10.1038/s41598-017-12756-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5622065PMC
September 2017

Binding position analysis of target proteins with the use of amidopyrene probes as LA-LDI enhancing tags.

Org Biomol Chem 2016 Sep 22;14(36):8564-9. Epub 2016 Aug 22.

Graduate School of Pure and Applied Sciences, University of Tsukuba, Japan.

Amidopyrene-conjugated compounds can be detected by label-assisted laser desorption/ionization mass spectrometry (LA-LDI MS) without matrixes. When actin, a cytoskeletal protein, was labeled with an excess amount of amidopyrene N-hydroxysuccinate (apy-OSu), eight apy-labeled actin peptides were predominantly detected by LA-LDI MS. Then actin was labeled with an amidopyrene NHS ester of the antitumor marine macrolide aplyronine A (ApA-apy-OSu) to form a 1 : 1 conjugate. The sequence of an apy-labeled peptide was established as A(108)PLNPKANR(116) by MS/MS analysis, in which the NHS ester moiety specifically reacted with the ε-amino group of K113. While the fragmentation at the linker part reduces the detection sensitivity of apy-labeled peptides on LA-LDI MS, our chemical probe method is useful for analyzing the binding modes of various ligands and target biomacromolecules that include multiple and weak interactions.
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http://dx.doi.org/10.1039/c6ob01381cDOI Listing
September 2016

Inherited ichthyosis: Syndromic forms.

Authors:
Kozo Yoneda

J Dermatol 2016 Mar;43(3):252-63

Department of Dermatology, Faculty of Medicine, Kagawa University, Kagawa, Japan.

Among diseases that cause ichthyosis as one of the symptoms, there are some diseases that induce abnormalities in organs other than the skin. Of these, diseases with characteristic signs are regarded as syndromes. Although these syndromes are very rare, Netherton syndrome, Sjögren-Larsson syndrome, Conradi-Hünermann-Happle syndrome, Dorfman-Chanarin syndrome, ichthyosis follicularis, atrichia and photophobia (IFAP) syndrome, and Refsum syndrome have been described in texts as representative ones. It is important to know the molecular genetics and pathomechanisms in order to establish an effective therapy and beneficial genetic counseling including a prenatal diagnosis.
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http://dx.doi.org/10.1111/1346-8138.13284DOI Listing
March 2016

Case of a self-inflicted facial ulcer that improved after sepsis.

J Dermatol 2016 May 24;43(5):576-7. Epub 2015 Dec 24.

Department of Dermatology, Faculty of Medicine, Kagawa University, Kagawa, Japan.

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http://dx.doi.org/10.1111/1346-8138.13244DOI Listing
May 2016

6-Amidopyrene as a label-assisted laser desorption/ionization (LA-LDI) enhancing tag: development of photoaffinity pyrene derivative.

Sci Rep 2015 Dec 15;5:17853. Epub 2015 Dec 15.

Graduate School of Pure and Applied Sciences, University of Tsukuba.

Pyrene-conjugated compounds are detected by label-assisted laser desorption/ionization mass spectrometry (LA-LDI MS) without matrixes. We found that 6-amidopyrene derivatives were highly detectable by the LDI MS instrument equipped with a 355 nm laser. In a certain case of a 6-amidopyrene derivative, a molecular ion peak [M](+•) and a characteristic fragment ion peak [M-42](+•) were detected in an amount of only 10 fmol. The latter peak, corresponding to the 6-aminopyrene fragment, might be generated in situ by the removal of ketene (CH2=C=O) from the parent molecule. A photoaffinity amidopyrene derivative of an antitumor macrolide aplyronine A (ApA-PaP) was synthesized, which showed potent cytotoxicity and actin-depolymerizing activity. In an LDI MS analysis of the MeOH- and water-adducts of ApA-PaP, oxime N-O bonds as well as amidopyrene N-acetyl moieties were preferentially cleaved, and their internal structures were confirmed by MS/MS analysis. Amidopyrene moiety might enhance fragmentation and stabilize the cleaved fragments by intramolecular or intermolecular weak interactions including hydrogen bonding. Our chemical probe methods might contribute to a detailed analysis of binding modes between various ligands and target biomacromolecules that include multiple and weak interactions.
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http://dx.doi.org/10.1038/srep17853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678867PMC
December 2015

Comorbidity of dermatofibromas and mucinous nevi.

Int J Dermatol 2016 Jan 16;55(1):e53-5. Epub 2015 Oct 16.

Department of Dermatology, Faculty of Medicine, Kagawa University, Kagawa, Japan.

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http://dx.doi.org/10.1111/ijd.13015DOI Listing
January 2016

Lupus pernio-like skin metastasis of adenocarcinoma.

Int J Dermatol 2015 Dec 4;54(12):e543-5. Epub 2015 Sep 4.

Department of Dermatology, Faculty of Medicine, Kagawa University, Kagawa, Japan.

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http://dx.doi.org/10.1111/ijd.12934DOI Listing
December 2015

βKlotho expression is reduced in human non-melanoma skin cancer.

Int J Dermatol 2015 Oct 31;54(10):e431-3. Epub 2015 Jul 31.

Department of Dermatology, Faculty of Medicine, Kagawa University, Kagawa, Japan.

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http://dx.doi.org/10.1111/ijd.12924DOI Listing
October 2015

Cellulitis-like skin eruption of purulent tenosynovitis caused by Streptococcus dysgalactiae.

Acta Derm Venereol 2015 Apr;95(4):501-2

Department of Dermatology, Faculty of Medicine, Kagawa University, Kagawa, Japan.

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http://dx.doi.org/10.2340/00015555-1991DOI Listing
April 2015

Polycystic kidney disease with steatocystoma multiplex: evidences for a disruptive effect of mutated polycystin-1 on keratin 17 polymerisation.

Acta Derm Venereol 2015 Mar;95(3):353-4

Department of Dermatology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Kita-gun Miki-cho, 761-0793 Kagawa, Japan.

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http://dx.doi.org/10.2340/00015555-1934DOI Listing
March 2015

Transepidermal growth in disseminated Fusarium infection.

J Dermatol 2014 Aug 9;41(8):770-1. Epub 2014 Jul 9.

Department of Dermatology, Kagawa University, Kagawa, Japan.

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http://dx.doi.org/10.1111/1346-8138.12555DOI Listing
August 2014

Case of mucous membrane pemphigoid with autoantibodies solely to the γ2-subunit of laminin-332.

J Dermatol 2014 Aug 2;41(8):766-7. Epub 2014 Jul 2.

Faculty of Medicine, Department of Dermatology, Kagawa University, Kagawa.

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http://dx.doi.org/10.1111/1346-8138.12552DOI Listing
August 2014

Novel ATP2A2 mutation in a patient with Darier's disease.

J Dermatol 2014 Apr 24;41(4):349-50. Epub 2014 Feb 24.

Department of Dermatology, Faculty of Medicine, Kagawa University, Kagawa.

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http://dx.doi.org/10.1111/1346-8138.12437DOI Listing
April 2014

Multibranched acquired periungual fibrokeratoma.

JAMA Dermatol 2014 Apr;150(4):456-7

Department of Dermatology, Faculty of Medicine, Kagawa University, Kagawa, Japan.

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http://dx.doi.org/10.1001/jamadermatol.2013.6631DOI Listing
April 2014

Pachyonychia congenita in Japan: report of familial cases with a recurrent KRT16 mutation.

Eur J Dermatol 2014 Jan-Feb;24(1):122-3

Department of Dermatology, Kurume University School of Medicine, Fukuoka 830-0011, Japan.

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http://dx.doi.org/10.1684/ejd.2013.2244DOI Listing
February 2015

Two cases of nevus sebaceous accompanying secondary tumors with βKlotho expression.

J Dermatol 2014 Feb 16;41(2):171-2. Epub 2014 Jan 16.

Department of Dermatology, Kagawa University, Kagawa, Japan.

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http://dx.doi.org/10.1111/1346-8138.12371DOI Listing
February 2014

Inhibition of microtubule assembly by a complex of actin and antitumor macrolide aplyronine A.

J Am Chem Soc 2013 Dec 21;135(48):18089-95. Epub 2013 Nov 21.

Graduate School of Pure and Applied Sciences and ‡Graduate School of Life and Environmental Sciences, University of Tsukuba , 1-1-1 Tennodai, Tsukuba 305-8571, Japan.

Aplyronine A (ApA) is a marine natural product that shows potent antitumor activity. While both ApA and ApC, a derivative of ApA that lacks a trimethylserine ester moiety, inhibit actin polymerization in vitro to the same extent, only ApA shows potent cytotoxicity. Therefore, the molecular targets and mechanisms of action of ApA in cells have remained unclear. We report that ApA inhibits tubulin polymerization in a hitherto unprecedented way. ApA forms a 1:1:1 heterotrimeric complex with actin and tubulin, in association with actin synergistically binding to tubulin, and inhibits tubulin polymerization. Tubulin-targeting agents have been widely used in cancer chemotherapy, but there are no previous descriptions of microtubule inhibitors that also bind to actin and affect microtubule assembly. ApA inhibits spindle formation and mitosis in HeLa S3 cells at 100 pM, a much lower concentration than is needed for the disassembly of the actin cytoskeleton. The results of the present study indicate that ApA represents a rare type of natural product, which binds to two different cytoplasmic proteins to exert highly potent biological activities.
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http://dx.doi.org/10.1021/ja406580wDOI Listing
December 2013

Deranged epidermal differentiation in kl/kl mouse and the effects of βKlotho siRNA on the differentiation of HaCaT cells.

Exp Dermatol 2013 Nov;22(11):772-4

Department of Dermatology, Kagawa University, Kita-Gun, Japan.

Mice deficient in the klotho gene (kl/kl mice) display the phenotypes of human ageing. We found that the expression of epidermal differentiation-associated factors (keratin 1, keratin 10, filaggrin and loricrin) was lower in the skin of kl/kl mice than that of wild-type mice. In vitro experiments showed that the expression of βKlotho, a family of klotho gene-encoded protein, was induced concomitantly with the differentiation of an immortalized human epidermal keratinocyte cell line (HaCaT cells) when they were cultured in an air-liquid interface. βKlotho knockdown by small interfering ribonucleic acid suppressed the expression of the above differentiation-associated factors in HaCaT cells. βKlotho small interfering ribonucleic acid increased the expression of keratin 14, which is expressed in mitotically active basal layer cells, and activated p44/p42 mitogen-activated protein kinase in the HaCaT cells grown in the air-liquid interface. These findings suggest that the epidermal differentiation is deranged in kl/kl mice, and βKlotho is required for the differentiation of human epidermal keratinocytes.
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http://dx.doi.org/10.1111/exd.12258DOI Listing
November 2013
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