Search

The article focuses on a case report detailing the rare occurrence of cutaneous intestinal metaplasia in the urostomy area of a patient who underwent a cystectomy with ileal conduit urinary diversion, highlighting the histopathological findings, and differentiation from other skin lesions. It discusses the unique manifestation of cutaneous intestinal metaplasia triggered by continuous urine contact, emphasizing the importance of histological examination for refractory peristomal lesions.

During embryonic development or under certain pathological conditions, viable but suboptimal cells are often eliminated from the cellular society through a process termed cell competition. Cell competition was originally identified in Drosophila where cells with different properties compete for survival; 'loser' cells are eliminated from tissues and consequently 'winner' cells become dominant. Recent studies have shown that cell competition also occurs in mammals. While apoptotic cell death is the major fate for losers in Drosophila, outcompeted cells show more variable phenotypes in mammals, such as cell death-independent apical extrusion and cellular senescence. Molecular mechanisms underlying these processes have been recently revealed. Especially, in epithelial tissues, normal cells sense and actively eliminate the neighbouring transformed cells via cytoskeletal proteins by the process named epithelial defence against cancer (EDAC). Here, we introduce this newly emerging research field: cell competition in mammals. [ABSTRACT FROM AUTHOR]

Attempts to treat congenital protein deficiencies using bone marrow-derived cells have been reported. These efforts have been based on the concepts of stem cell plasticity. However, it is considered more difficult to restore structural proteins than to restore secretory enzymes. This study aims to clarify whether bone marrow trans- plantation (BMT) treatment can rescue epidermolysis bullosa (EB) caused by defects in keratinocyte structural proteins. BMT treatment of adult collagen XVII (Col17) knockout mice induced donor-derived keratinocytes and Col17 expression associated with the recovery of hemidesmosomal structure and better skin manifestations, as well improving the survival rate. Both hematopoietic and mesenchymal stem cells have the potential to produce Col17 in the BMT treatment model. Furthermore, human cord blood CD34+ cells also differentiated into keratinocytes and expressed human skin component proteins in transplanted immunocompromised (NOD/SClD/γcnull) mice. The current conventional BMT techniques have significant potential as a systemic therapeutic approach for the treatment of human EB. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 54-year-old Japanese woman presented with multiple nodules arising within a hairless birthmark on her head. It mentions that past medical history of the patient as unremarkable, with no neurological, skeletal or congenital anomalies. It mentions that scanning view of the surgical specimen revealed multiple dermal nodules within a melanocytic naevus.

The article present a case study of an 82-year-old Japanese woman with a 1-week history of necrolytic ulcers on the lower legs. Physical examination revealed reddish-violaceous ulcers, in size of 15 cm with yellow or black necrolytic tissue surrounded by disseminated blood blisters and purpura on the flexor surfaces of the lower legs; and mentions a chest X-ray showed mild infiltrates in the left lower lung.

An answer is presented to a question on diagnosis in infant girl who presented with asymptomatic papules on her entire body.

The article describes the case of a 16-year-old Japanese boy with a history of ganglion cyst, presented with a subcutaneous nodule on his right palm. Topics discussed include the results of clinical examination on the patient, performance of surgical excision on the patient under the clinical diagnosis of recurrent ganglion cyst, proliferation of atypical cells with vesicular nuclei and mild myxoid areas and diagnosis of myxoinflammatory fibblastic sarcoma (MIES).

The article describes the case of a 55-year-old Japanese female patient with a history of pure red cell aplasia and who developed thymoma-associated multi-organ autoimmunity (TAMA). The diagnosis is confirmed after performing physical examination, immunohistochemical, histopathological and indirect immunofluorescence (IIF) analyses. A discussion on the mechanism responsible for the development of graft-versus-host disease (GVHD)-life reaction in thymoma is offered.

This article describes a case study of tubular Spitz naevus. The patient presented with an asymptomatic reddish nodule, which had been present for two months. Clinicopathological findings revealed tubular Spitz naevus that resembled ependymal rosette in neurogenic neoplasms and partly resembled eccrine spiradenoma. The clinical management of the patient is detailed.

In various epithelial tissues, the epithelial monolayer acts as a barrier. To fulfill its function, the structural integrity of the epithelium is tightly controlled. When normal epithelial cells detach from the basal substratum and delaminate into the apical lumen, the apically extruded cells undergo apoptosis, which is termed anoikis. In contrast, transformed cells often become resistant to anoikis and able to survive and grow in the apical luminal space, leading to the formation of multilayered structures, which can be observed at the early stage of carcinogenesis. However, the underlying molecular mechanisms still remain elusive. In this study, we first demonstrate that S100A10 and ANXA2 (Annexin A2) accumulate in apically extruded, transformed cells in both various cell culture systems and murine epithelial tissues in vivo. ANXA2 acts upstream of S100A10 accumulation. Knockdown of ANXA2 promotes apoptosis of apically extruded RasV12-transformed cells and suppresses the formation of multilayered epithelia. In addition, the intracellular reactive oxygen species (ROS) are elevated in apically extruded RasV12 cells. Treatment with ROS scavenger Trolox reduces the occurrence of apoptosis of apically extruded ANXA2-knockdown RasV12 cells and restores the formation of multilayered epithelia. Furthermore, ROS-mediated p38MAPK activation is observed in apically delaminated RasV12 cells, and ANXA2 knockdown further enhances the p38MAPK activity. Moreover, the p38MAPK inhibitor promotes the formation of multilayered epithelia of ANXA2-knockdown RasV12 cells. These results indicate that accumulated ANXA2 diminishes the ROS-mediated p38MAPK activation in apically extruded transformed cells, thereby blocking the induction of apoptosis. Hence, ANXA2 can be a potential therapeutic target to prevent multilayered, precancerous lesions. [ABSTRACT FROM AUTHOR]

Nail-patella syndrome is an autosomal dominant disorder characterized by nail dysplasia and skeletal anomaly. Some patients have been shown to have ultrastructural abnormalities of the glomerular basement membrane that result in nephrosis. However, little has been reported on the epidermal basement membrane in this condition. This paper reports 2 families with nail-patella syndrome. Direct sequencing analysis of LMX1B revealed that family 1 and family 2 were heterozygous for the mutations c.140-1G>C and c.326+1G>C, respectively. To evaluate the epidermal basement membrane zone, ultrastructural and immunohistochemical analyses were performed using skin specimens obtained from the dorsal thumb. Electron microscopy showed intact hemidesmosomes, lamina lucida, lamina densa, and anchoring fibrils. Immunofluorescence studies with antibodies against components of the epidermal basement membrane zone revealed a normal expression pattern among the components, including type IV collagen. These data suggest that nail dysplasia in patients with nail-patella syndrome is not caused by structural abnormalities of the epidermal basement membrane. [ABSTRACT FROM AUTHOR]

Cell competition is involved in mammalian embryogenesis and tumor elimination and progression. It was previously shown that, whereas NIH3T3 mouse fibroblasts expressing high levels of the yes-associated protein 1(YAP1) target TEA domain family (TEAD) transcription factors become "winners" in cell competitions, Madin-Darby canine kidney cells expressing activated YAP1 become "losers" and are eliminated from culture monolayers. Thus, YAP1's role in cell competitions is clearly context dependent. Here, we show that keratinocytes overexpressing a constitutively activated YAP1 mutant lose in in vitro competitions with control cells conducted in standard tissue culture dishes and undergo apical extrusion. Similarly, cells in which endogenous YAP1 is activated by NF2 knockdown become losers. The YAP1-overexpressing cells exhibit a decrease in cell-matrix adhesion because of defective expression of adhesion molecules such as fibronectin-1. Cell adhesion-mediated proliferation is also impaired. However, because of intrinsic factors, YAP1-expressing cells proliferate faster than control cells when cocultured in dishes impeding cell adhesion. In vivo, Mob1a/b-deficient (YAP1-activated) epidermis, which shows decreased expression of type XVII collagen, cannot be engrafted successfully onto donor mice. YAP1-activated skin grafts shrink away from surrounding control skin, and the epidermis peels off the basement membrane. Our data show that YAP1 activation controls cell competition in part by decreasing cell adhesion. [ABSTRACT FROM AUTHOR]

This article describes a case study of recessive dystrophic epidermolysis bullosa (RDEB) successfully treated with cultured epidermal autograft (CEA). The patient presented with generalized blisters induced by minor trauma since birth. At three days after the CEA procedure, spotted epithelialization was observed on the right knee and at two weeks, almost full re-epithelialization was observed.

Newly emerging transformed cells are often eliminated from epithelial tissues. Recent studies have revealed that this cancer-preventive process involves the interaction with the surrounding normal epithelial cells; however, the molecular mechanisms underlying this phenomenon remain largely unknown. In this study, using mammalian cell culture and zebrafish embryo systems, we have elucidated the functional involvement of endocytosis in the elimination of RasV12-transformed cells. First, we show that Rab5, a crucial regulator of endocytosis, is accumulated in RasV12-transformed cells that are surrounded by normal epithelial cells, which is accompanied by upregulation of clathrin-dependent endocytosis. Addition of chlorpromazine or coexpression of a dominant-negative mutant of Rab5 suppresses apical extrusion of RasV12 cells from the epithelium. We also show in zebrafish embryos that Rab5 plays an important role in the elimination of transformed cells from the enveloping layer epithelium. In addition, Rab5-mediated endocytosis of E-cadherin is enhanced at the boundary between normal and RasV12 cells. Rab5 functions upstream of epithelial protein lost in neoplasm (EPLIN), which plays a positive role in apical extrusion of RasV12 cells by regulating protein kinase A. Furthermore, we have revealed that epithelial defense against cancer (EDAC) from normal epithelial cells substantially impacts on Rab5 accumulation in the neighboring transformed cells. This report demonstrates that Rab5-mediated endocytosis is a crucial regulator for the competitive interaction between normal and transformed epithelial cells in mammals. [ABSTRACT FROM AUTHOR]

At the initial stage of carcinogenesis, a mutation occurs in a single cell within a normal epithelial layer. We have previously shown that RasV12-transformed cells are apically extruded from the epithelium when surrounded by normal cells. However, the molecular mechanisms underlying this phenomenon remain elusive. Here, we demonstrate that Cav-1-containing microdomains and EPLIN (also known as LIMA1) are accumulated in RasV12-transformed cells that are surrounded by normal cells. We also show that knockdown of Cav-1 or EPLIN suppresses apical extrusion of RasV12-transformed cells, suggesting their positive role in the elimination of transformed cells from epithelia. EPLIN functions upstream of Cav-1 and affects its enrichment in RasV12-transformed cells that are surrounded by normal cells. Furthermore, EPLIN regulates non-cell-autonomous activation of myosin-II and protein kinase A (PKA) in RasV12- transformed cells. In addition, EPLIN substantially affects the accumulation of filamin A, a vital player in epithelial defense against cancer (EDAC), in the neighboring normal cells, and vice versa. These results indicate that EPLIN is a crucial regulator of the interaction between normal and transformed epithelial cells. [ABSTRACT FROM AUTHOR]

The article describes the case of an 18-year-old Japanese male patient with a history of bilateral, well-defined erythematous hyperkerotic lesions on his extremities and lumbar area, and who developed a Nagashima-type palmoplantar keratosis (NPPK). The diagnosis is confirmed after performing physical examination, histology of lesional skin and mutational analysis. A discussion on the role fo mutation in SERPINB7 gene in the occurrence of NPPK is offered.

The article describes the case of a 24-year-old Japanese woman diagnosed with lymphomatoid papulosis (LyP) type D, a histopathological variant simulating a primary cutaneous aggressive epidermotropic CD8 cytotoxic T-cell lymphoma. Topics discussed include the clinical characteristics of LyP, medical history of the patient, results of several tests performed on the patient including physical and laboratory and positive differential diagnosis of the case.