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2.
Phys Rev Lett ; 109(15): 157006, 2012 Oct 12.
Article in English | MEDLINE | ID: mdl-23102358

ABSTRACT

We report a highly unusual angular variation of the upper critical field (H(c2)) in epitaxial superlattices CeCoIn(5)(n)/YbCoIn(5)(5), formed by alternating layers of n and a 5 unit-cell thick heavy-fermion superconductor CeCoIn(5) with a strong Pauli effect and normal metal YbCoIn(5), respectively. For the n=3 superlattice, H(c2)(θ) changes smoothly as a function of the field angle θ. However, close to the superconducting transition temperature, H(c2)(θ) exhibits a cusp near the parallel field (θ=0°). This cusp behavior disappears for n=4 and 5 superlattices. This sudden disappearance suggests the relative dominance of the orbital depairing effect in the n=3 superlattice, which may be due to the suppression of the Pauli effect in a system with local inversion symmetry breaking. Taking into account the temperature dependence of H(c2)(θ) as well, our results suggest that some exotic superconducting states, including a helical superconducting state, might be realized at high magnetic fields.

5.
Gene Ther ; 18(9): 857-66, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21490680

ABSTRACT

In vitro culture systems of human myogenic cells contribute greatly to elucidation of the molecular mechanisms underlying terminal myogenic differentiation and symptoms of neuromuscular diseases. However, human myogenic cells have limited ability to proliferate in culture. We have established an improved immortalization protocol for human myogenic cells derived from healthy and diseased muscles; constitutive expression of mutated cyclin-dependent kinase 4, cyclin D1 and telomerase immortalized human myogenic cells. Normal diploid chromosomes were preserved after immortalization. The immortalized human myogenic cells divided as rapidly as primary human myogenic cells during the early passages, and underwent myogenic, osteogenic and adipogenic differentiation under appropriate culture conditions. The immortalized cells contributed to muscle differentiation upon xenotransplantation to immunodeficient mice under conditions of regeneration following muscle injury. We also succeeded in immortalizing cryopreserved human myogenic cells derived from Leigh disease patients following primary culture. Forced expression of the three genes shortened their cell cycle to < 30 h, which is similar to the doubling time of primary cultured human myogenic cells during early passages. The immortalization protocol described here allowed human myogenic cells to recapture high proliferation activity without compromising their differentiation potential and normal diploidy.


Subject(s)
Cell Line, Transformed , Cyclin D1/genetics , Cyclin-Dependent Kinase 4/genetics , Satellite Cells, Skeletal Muscle/physiology , Animals , Cell Cycle , Cell Differentiation , Cell Division , Humans , Leigh Disease/genetics , Mice , Mutation , Osteogenesis
7.
Neurology ; 73(15): 1214-7, 2009 Oct 13.
Article in English | MEDLINE | ID: mdl-19822871

ABSTRACT

OBJECTIVE: Mutations of the genes encoding subunits of potassium voltage-gated channel, KCNQ2 and KCNQ3, have been identified in patients with benign familial neonatal seizures (BFNS). This study set out to determine the frequency of microchromosomal deletions of KCNQ2 or KCNQ3 associated with BFNS. METHODS: The study subjects were patients with BFNS (n = 22). Microdeletions were sought by multiplex ligation-dependent probe amplification and then confirmed by fluorescence in situ hybridization and characterized by array-based comparative genomic hybridization. RESULTS: Heterozygous multiple exonic deletions of KCNQ2 were identified in 4 of 22 patients with BFNS. Concomitant deletions of adjacent genes, including nicotinic cholinergic receptor alpha4 (CHRNA4), were detected in 2 of the 4 cases. The clinical courses of patients with deletions of both KCNQ2 and CHRNA4 were those of typical BFNS, and none presented with the phenotype of autosomal dominant nocturnal frontal lobe epilepsy, some of which are caused by mutations of CHRNA4. CONCLUSIONS: Our findings indicate that the clinical courses of patients with deletions of both KCNQ2 and CHRNA4 are indistinguishable from those of patients with deletions of KCNQ2 only.


Subject(s)
Chromosome Deletion , Chromosomes, Human, Pair 20/genetics , Epilepsy, Benign Neonatal/genetics , KCNQ2 Potassium Channel/genetics , Receptors, Nicotinic/genetics , Adolescent , Adult , Aged , Child , Female , Humans , KCNQ3 Potassium Channel/genetics , Male , Middle Aged , Models, Genetic , Pedigree
8.
Sex Dev ; 3(4): 225-32, 2009.
Article in English | MEDLINE | ID: mdl-19752602

ABSTRACT

Exogenous factors such as temperature, social behavior, and salinity play a crucial role during the critical sensitive period of sex differentiation in many vertebrates. In fishes, amphibians, and reptiles temperature treatment is known to induce all-male (or female) individuals, and genes related to sex differentiation have been studied. The Japanese pufferfish, Takifugu rubripes, possesses the most compact genome among vertebrates and has immense potential for studies focusing on comparative genome analysis. In this study, we describe gonadal morphology and vasa (germ cell marker) and dmrt1 (Sertoli cell marker) expression on a molecular level in relation to the development of temperature-treated pufferfish. To investigate the relationship between temperature and gonadal development, pufferfish were exposed to high-temperature conditions (32 degrees C) during early gonadal development. Morphological observations showed that this high-temperature treatment did not influence sexual differentiation as determined by ovarian cavity characteristics; however, high-temperature treatment induces gonadal degeneration that is devoid of germ cells. RT-PCR results revealed no vasa expression within germ cell-degenerated gonads. In situ hybridization results showed that dmrt1 was expressed in somatic cells of germ cell-degenerated ovaries. These results suggest that high-temperature treatment during early gonadal development induces germ cell degeneration and masculinization of ovarian somatic cells in pufferfish.


Subject(s)
Germ Cells/cytology , Takifugu/growth & development , Temperature , Animals , Body Weight , Cell Death , DEAD-box RNA Helicases/genetics , DEAD-box RNA Helicases/metabolism , Female , Gene Expression Regulation, Developmental , Germ Cells/enzymology , Gonads/cytology , Gonads/enzymology , Gonads/growth & development , In Situ Hybridization , Male , Transcription Factors/genetics , Transcription Factors/metabolism
10.
Clin Exp Dermatol ; 33(5): 641-3, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18627388

ABSTRACT

Only a few reports have been published of detailed clinical studies of pemphigus in Japan. The aim of this study was to determine the clinical characteristics of patients with pemphigus vulgaris (PV) and pemphigus foliaceous (PF), who were newly diagnosed in the dermatology department of Kurume University Hospital, Japan, over the past 11 years. The primary site of involvement was the oral mucosa in 21 patients (75%) with PV. At the initial visit, most of the patients with PV had moderate to severe disease. With regard to management, systemic corticosteroids were the mainstay of treatment for patients with PV, and plasmapheresis was the most frequently used adjuvant therapy. Dapsone was the mainstay of treatment for the patients with PF. The patients were investigated for any association with an underlying malignancy; in patients with PV, lung, stomach and uterine cancers (one patient each) were seen.


Subject(s)
Pemphigus , Adrenal Cortex Hormones/therapeutic use , Adult , Anti-Infective Agents/therapeutic use , Dapsone/therapeutic use , Diagnosis, Differential , Female , Humans , Japan/epidemiology , Male , Middle Aged , Pemphigus/drug therapy , Pemphigus/epidemiology , Pemphigus/pathology , Retrospective Studies
15.
Br J Dermatol ; 155(3): 586-91, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16911286

ABSTRACT

BACKGROUND: The insulin-like growth factor-1 (IGF-1) receptor (R)-induced phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK)/ERK signal transduction cascade, which have critical roles in prevention of apoptosis and regulation of cell cycle progression, plays an important role in tumorigenesis. The expression of IGF-1R, AKT and ERK1/2 has been described in some human malignancies, but not in extramammary Paget's disease (EMPD). OBJECTIVES: To study the expression of IGF-1R, p-AKT and p-ERK1/2 in EMPD and to evaluate the relationships among them. METHODS: Thirty-six tissue samples of 34 patients with primary EMPD were subjected to immunohistochemical staining for IGF-1R, p-AKT and p-ERK1/2. RESULTS: Of thirty-six EMPD tissue samples, 34, 34 and 28 were positive for IGF-IR, p-AKT and p-ERK1/2 expression, respectively; 27, 23 and 17 of the 36 specimens stained positive for IGF-IR, p-AKT and p-ERK1/2 in more than half of Paget's cells, respectively. There were significant correlations between the IGF-1R and p-AKT expression as well as between IGF-1R and p-ERK1/2 expression. Taken together, these results indicate that IGF-1R is overexpressed, and AKT and ERK1/2 are frequently phosphorylated in EMPD. CONCLUSIONS: Our study shows that the expression of IGF-1R and the induction of p-AKT and the p-ERK1/2 pathway may play an important role in the pathogenesis of EMPD. The IGF-IR system might be a potential therapeutic target in EMPD.


Subject(s)
Neoplasm Proteins/metabolism , Paget Disease, Extramammary/metabolism , Skin Neoplasms/metabolism , Aged , Aged, 80 and over , Female , Humans , Immunoenzyme Techniques , Lymphatic Metastasis , Male , Middle Aged , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Neoplasm Invasiveness , Paget Disease, Extramammary/pathology , Paget Disease, Extramammary/secondary , Proto-Oncogene Proteins c-akt/metabolism , Receptor, IGF Type 1/metabolism , Signal Transduction , Skin Neoplasms/pathology
16.
Br J Dermatol ; 154(5): 926-32, 2006 May.
Article in English | MEDLINE | ID: mdl-16634897

ABSTRACT

BACKGROUND: Stat3 (Signal transducer and activator of transcription-3) is an oncogene that plays a critical role in regulating fundamental processes associated with malignant transformation and cell survival. It participates in oncogenesis through upregulation of genes encoding apoptosis inhibitors (Bcl-xL) and cell cycle regulators (cyclin D1). The expression of Stat3, Bcl-xL and cyclin D1 protein has not been investigated in extramammary Paget disease (EMPD). OBJECTIVES: To study the expression of phosphorylated Stat3 (p-Stat3), Bcl-xL and cyclin D1 protein in EMPD and to evaluate the relationships among them. METHODS: Thirty-six tissue samples from 34 patients with primary EMPD were subjected to immunohistochemical staining for p-Stat3, cyclin D1 and Bcl-xL. RESULTS: Thirty-five of 36 specimens were clearly positive for p-Stat3 in EMPD, while 30 of 36 and 32 of 36 were positive for cyclin D1 and Bcl-xL expression, respectively. In all of four invasive EMPD specimens, strong and frequent expression of these three molecules was evident; moreover, two invasive EMPD specimens with lymph nodal metastasis showed very strong nuclear and membranous p-Stat3 staining. Two metastatic lymph node specimens showed very strong nuclear and local membrane p-Stat3 staining. There were significant correlations between p-Stat3 and cyclin D1 expression and between p-Stat3 and Bcl-xL expression. CONCLUSIONS: Our study shows that the expression of p-Stat3, cyclin D1 and Bcl-xL may play a pivotal role in the pathogenesis of EMPD.


Subject(s)
Neoplasm Proteins/metabolism , Paget Disease, Extramammary/metabolism , STAT3 Transcription Factor/metabolism , Adult , Aged , Aged, 80 and over , Cyclin D1/metabolism , Female , Humans , Immunoenzyme Techniques , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Invasiveness , Paget Disease, Extramammary/pathology , Paget Disease, Extramammary/secondary , Phosphorylation , Skin/metabolism , bcl-X Protein/metabolism
18.
Neurology ; 63(2): 329-34, 2004 Jul 27.
Article in English | MEDLINE | ID: mdl-15277629

ABSTRACT

BACKGROUND AND METHODS: Many missense mutations in the voltage-gated sodium channel subunit gene SCN1A were identified in patients with generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI), although GEFS+ is distinct from SMEI in terms of clinical symptoms, severity, prognosis, and responses to antiepileptic drugs. The authors analyzed the localization of missense mutations in SCN1A identified in patients with GEFS+ and SMEI to clarify the phenotype-genotype relationships. RESULTS: Mutations in SMEI occurred more frequently in the "pore" regions of SCN1A than did those in GEFS+. These SMEI mutations in the "pore" regions were more strongly associated than mutations in other regions with the presence of ataxia and tendency to early onset of disease. The possibility of participation of ion selectivity dysfunction of the channel in the pathogenesis of SMEI was suggested by a mutation in the pore region (R946C) identified in a SMEI patient. CONCLUSIONS: There was a significant phenotype-genotype relationship in generalized epilepsy with febrile seizures plus and severe myoclonic epilepsy of infancy with SCN1A missense mutations. More severe sodium channel dysfunctions including abnormal ion selectivity that are caused by mutations in the pore regions may be involved in the pathogenesis of SMEI.


Subject(s)
Epilepsies, Myoclonic/genetics , Epilepsy, Generalized/genetics , Mutation, Missense , Nerve Tissue Proteins/genetics , Seizures, Febrile/genetics , Sodium Channels/genetics , Age of Onset , Amino Acid Sequence , Amino Acid Substitution , Ataxia/genetics , Female , Genetic Predisposition to Disease , Genotype , Humans , Infant , Ion Transport/physiology , Male , Models, Molecular , NAV1.1 Voltage-Gated Sodium Channel , Nerve Tissue Proteins/chemistry , Nerve Tissue Proteins/physiology , Phenotype , Point Mutation , Protein Structure, Tertiary , Sequence Alignment , Sodium Channels/chemistry , Sodium Channels/physiology
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