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Artigo em Inglês | MEDLINE | ID: mdl-31818947


Recessive dystrophic epidermolysis bullosa (RDEB) is a severe inherited skin disorder caused by mutations in the COL7A1 gene encoding type VII collagen (C7). The spectrum of severity depends on the type of mutation in the COL7A1 gene. C7 is the major constituent of anchoring fibrils (AFs) at the basement membrane zone (BMZ). Patients with RDEB lack functional C7 and have severely impaired dermal-epidermal stability, resulting in extensive blistering and open wounds on the skin that greatly affect the patient's quality of life. There are currently no therapies approved for the treatment of RDEB. Here, we demonstrated the correction of mutations in exon 19 (c.2470insG) and exon 32 (c.3948insT) in the COL7A1 gene through homology-directed repair (HDR). We used the clustered regulatory interspaced short palindromic repeats (CRISPR) Cas9-gRNAs system to modify induced pluripotent stem cells (iPSCs) derived from patients with RDEB in both the heterozygous and homozygous states. Three-dimensional human skin equivalents (HSEs) were generated from gene-corrected iPSCs, differentiated into keratinocytes (KCs) and fibroblasts (FBs), and grafted onto immunodeficient mice, which showed normal expression of C7 at the BMZ as well as restored AFs 2 mo postgrafting. Safety assessment for potential off-target Cas9 cleavage activity did not reveal any unintended nuclease activity. Our findings represent a crucial advance for clinical applications of innovative autologous stem cell-based therapies for RDEB.

Zootaxa ; 4624(4): zootaxa.4624.4.4, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31716198


Chelonocytherois omutai gen. et sp. nov., is found on the back of female loggerhead sea turtles on the nesting beach of the Yakushima Island, Kagoshima Prefecture, Japan. The present study provides the first species-level identification and description of Ostracoda as sea turtle epibionts. The new genus and species, which belongs to the family Paradoxostomatidae Brady and Norman, 1889, can clearly be distinguished from other genera by the morphology of the carapace and the appendages. Especially, the quite large sieve structure on the pore system of the carapace is characteristic to this genus. Although a similar structure is also found in the commensal ostracod genus Redekea de Vos, 1953, the new genus has distinctive mandibular and maxillular morphologies. From examination of the appendages, C. omutai gen. et sp. nov. seems to be an epibiotic species associated with sea turtles, but not a strictly commensal species. Additionally, the nearly complete 18S rRNA gene sequence is determined for C. omutai gen. et sp. nov. for future molecular phylogenetic studies. Since the sea turtles migrate across the oceans in their ontogenetic stages, they may play a role as a long-distance dispersal vector for C. omutai gen. et sp. nov.

Tartarugas , Animais , Crustáceos , Feminino , Ilhas , Japão , Oceanos e Mares , Filogenia
Zootaxa ; 4695(5): zootaxa.4695.5.7, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31719338


We describe the first occurrence of the widely occurring brittlestar Ophiactis savignyi (Müller Troschel, 1842) as epibionts on Caretta caretta (Linnaeus, 1758), the loggerhead sea turtles. On the sea turtle epibionts, the coronulid barnacles were well studied as listed in Hayashi (2013), and recently some crustaceans were collected from loggerhead sea turtles and described as new species (Tanabe et al. 2017; Tanaka and Hayashi 2019). In contrast, echinoderm epibionts listed from sea turtles are poorly understood (Table 1) and this study represents the novel discovery of an ophiuroid, which was not previously known to occur on the surface of this species.

Thoracica , Tartarugas , Animais , Equinodermos
J Am Acad Dermatol ; 79(6): 1039-1046, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29928911


BACKGROUND: Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. Early-stage MF patches or plaques often resemble inflammatory skin disorders (ISDs), including psoriasis and atopic dermatitis. Cell adhesion molecule 1 gene (CADM1), which was initially identified as a tumor suppressor gene in human non-small cell lung cancer, has been reported as a diagnostic marker for adult T-cell leukemia/lymphoma. OBJECTIVE: We investigated CADM1 expression in MF neoplastic cells, especially during early stages, and evaluated its usefulness as a diagnostic marker for MF. METHODS: We conducted a retrospective study by using immunohistochemical staining and confirmed the expression of CADM1 in MF. In addition, we compared CADM1 messenger RNA expression in microdissected MF samples and ISD samples. RESULTS: In the overall study period, 55 of 58 MF samples (94.8 %) stained positive for CADM1. None of the 50 ISD samples showed positive reactivity (P < .0001). We found CADM1 messenger RNA expression in the intradermal lymphocytes of patients with MF but not in those of patients with an ISD. LIMITATIONS: We did not conduct a validation study for MF cases in other institutions. CONCLUSIONS: CADM1-positive cells can be identified in early stages with fewer infiltrating cells and may be useful as a diagnostic marker for early-stage MF.

Biomarcadores Tumorais/análise , Molécula 1 de Adesão Celular/análise , Micose Fungoide/química , Proteínas de Neoplasias/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Molécula 1 de Adesão Celular/biossíntese , Molécula 1 de Adesão Celular/genética , Dermatite/metabolismo , Diagnóstico Precoce , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Japão/epidemiologia , Linfócitos/metabolismo , Linfócitos/patologia , Pessoa de Meia-Idade , Micose Fungoide/diagnóstico , Micose Fungoide/genética , Micose Fungoide/patologia , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Estadiamento de Neoplasias , RNA Mensageiro/biossíntese , RNA Neoplásico/biossíntese , Estudos Retrospectivos
J Dermatol ; 45(5): 613-617, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29464811


Autosomal recessive woolly hair is a relatively rare hereditary hair disorder characterized by sparse, short, curly hair. This condition is known to be caused by mutations in the LIPH gene, LPAR6 gene or KRT25 gene. In the Japanese population, most patients with autosomal recessive woolly hair carry one of two founder mutations in the LIPH gene, c.736T>A (p.Cys246Ser) or c.742C>A (p.His248Asn). However, occasionally, individuals with this condition carry compound heterozygous mutations, typically one founder mutation and another mutation. In this study, we describe a patient with a compound heterozygous mutation in the LIPH gene at c.736T>A and c.1095-3C>G. The latter mutation created a novel splice site. This was the fourth splice site mutation to be described in the LIPH gene. Furthermore, we performed an in vitro transcription assay in cultured cells, and demonstrated that the c.1095-3C>G mutation led to a frame-shift, which created a premature termination codon at the protein level (p.Glu366Ilefs*7). Finally, we summarized the mutations previously reported for the LIPH gene. Our findings provide further clues as to the molecular basis of autosomal recessive woolly hair.

Doenças do Cabelo/genética , Cabelo/anormalidades , Hipotricose/genética , Lipase/genética , Sítios de Splice de RNA/genética , Pré-Escolar , Códon sem Sentido , Análise Mutacional de DNA , Mutação da Fase de Leitura , Heterozigoto , Humanos , Masculino
Zootaxa ; 4353(1): 146-160, 2017 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-29245529


We describe Hexapleomera urashima sp. nov. from the carapaces of loggerhead sea turtles (Caretta caretta) on Yakushi-ma Island, southwestern Japan, the primary nesting site for the North Pacific population of this turtle. Hexapleomera urashima closely resembles H. edgari Bamber collected from Australian loggerheads (South Pacific population), sharing a uropod with four articles and maxillipedal endites with distal spiniform setae, but differs in having the maxillipedal coxa with two simple setae, the maxillipedal endite with two tiny dorsosubdistal and two distal spiniform setae, the labial palp fused to the outer lobe of the labium, and the basal article of pleopod 3 without inner setae. Several characters (e.g., size or presence/absence of a dorsal triangular process on the male fixed finger; number of inner setae on the pleopodal endopod), assumed to be diagnostic for species in Hexapleomera, actually vary within H. urashima, indicating that reassessment of species diagnoses is warranted. Hexapleomera urashima showed two COI haplotypes differing by one substitution, but separated from representatives of four other genera by 32.2-48.4% K2P distance. Indices of saturation substitution indicated that COI is not useful for phylogeny reconstruction within Tanaididae.

Tartarugas , Animais , Austrália , Crustáceos , Ilhas , Japão , Masculino