Teiichi Masuda

Photocured, styrenated gelatin-based microspheres for de novo adipogenesis through corelease of basic fibroblast growth factor, insulin, and insulin-like growth factor I.

De novo adipose tissue formation appears to proceed via two different biological events: neovascularization and spontaneous accumulation of preadipocytes and subsequent differentiation to mature adipocytes. In this article, we perform accelerated de novo adipose tissue engineering using photocured, styrenated, gelatin-based microspheres (SGMs) with different drug release rates of immobilized angiogenic and adipogenic factors. The concept of this system is to induce neovascularization and migration of endogenous preadipocytes by the rapid delivery of the angiogenic factor basic fibroblast growth factor (bFGF), followed by the proliferation and differentiation of preadipocytes into adipocytes by the prolonged delivery of the adipogenic factors, insulin and insulin-like growth factor I (IGF-I). Bioactive substance-immobilized SGMs with different drug release rates were prepared with different gelatin concentrations. An in vitro study showed the prolonged release of an immobilized model protein and the dependence of drug release rate on gelatin concentration. After the subcutaneous injections of SGMs immobilized with these bioactive substances in different combinations, the formation of masses or clusters of adipocytes was observed in rats. Triglyceride content in the injection site for the group that received bFGF-, insulin-, and IGF-I-immobilized SGMs was significantly higher than that for the group that received insulin- and IGF-I-immobilized SGMs 4 weeks after the injection of microspheres. These results suggest that the system developed here is effective for the de novo formation of adipose tissue as it enables the induction of the two-step biological reaction by single injection.

Pilomatricoma-like changes in the epidermoid cysts of Gardner syndrome with an APC gene mutation.

To the Editor: Gardner syndrome is an autosomal dominant disorder characterized by familial adenomatous colonic polyposis with several extra-intestinal manifestations (cutaneous, ophthalmologic, osseous, dental, etc.) including multiple epidermoid cysts. Cooper and Fechner (1) reported pilomatricoma-like changes were observed in the epidermal cysts of Gardner syndrome. We experienced a similar case of Gardner syndrome. We performed immunochemical staining of cells with pilomatricoma-like changes for beta-catenin, and found accumulation of beta-catenin in the cytoplasm and nucleus of the cells, and our results suggested that pilomatricomas might be caused by a mutation of the APC tumor suppressor gene. A 39-year-old female presented with multiple subcutaneous nodules at the Department of Dermatology of our hospital for surgical excision of these nodules (Fig. 1). She was first noted to have multiple subcutaneous nodules at 3 years of age and she had had several operations to remove some of these nodules at a dermatological clinic. At the age of 23 years, since her brother was diagnosed as adenomatous colonic polyposis, she underwent colonic examination at our hospital, and multiple colonic polyps were found. A subtotal colectomy was performed at the age of 28 years. Osteoma in the nasal cavity was detected by computed tomography at the age of 30 years. On the basis of these observations, she was diagnosed as Gardner syndrome. Physical examination revealed numerous subcutaneous nodules of 1 to 5 cm in diameter on her trunk, extremities and scalp. Twenty nodules were excised. On The Journal of Dermatology Vol. 31: 255–257, 2004

Expression of phosphorylated Stat3, cyclin D1 and Bcl-xL in extramammary Paget disease

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).

Basal Cell Carcinomas in Association with Basaloid Follicular Hamartoma

We describe a unique case of various types of basal cell carcinoma (BCC) associated with basaloid follicular hamartoma (BFH) in a 56-year-old female patient. The lesion consisted of a dark brown and elastic soft nodule and papules within the area of a birthmark on the neck. The lesion was surgically excised. Histological examination of the nodular region revealed aggregations of neoplastic basaloid cells. We diagnosed the nodule as BCC with a racemiform or reticular pattern. In addition, a specimen taken from brownish black papules within the birthmark was found to be composed of anastomosing cords of basaloid cells accompanied by infundibular cystic structures. These features were consistent with an infundibulocystic BCC. In contrast, specimens from a hamartomatous plaque showed distinctive branching strands of basaloid cells that are suggestive of BFH. Therefore, our findings indicate that several types of BCC may develop within a BFH.

Expression of insulin-like growth factor-1 receptor, p-AKT and p-ERK1/2 protein in extramammary Paget's disease.

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 Pagets disease (EMPD).

Expression of p16 and hTERT protein is associated with the presence of high-risk human papillomavirus in Bowenoid papulosis.

Background:  High‐risk human papillomavirus (hrHPV) type E6 and E7 oncoproteins contribute to oncogenesis in multiple ways by modulating the activities of host components in cell‐cycle regulation including the expression of p16 protein (p16) and human telomerase reverse transcriptase (hTERT). The expression of p16 and hTERT protein in Bowenoid papulosis (BP) has not been studied.

The prognostic value of a reverse transcriptase-PCR assay of sentinel lymph node biopsy for patients with cutaneous melanoma: A single-center analysis in Japan

Sentinel lymph node biopsy (SLNB) is the standard of care for staging melanoma. However, limited research has been carried out on the prognostic value of SLNB in patients with primary cutaneous melanoma in Asian countries. The objective is to evaluate the efficacy of SLNB in Japanese patients with primary cutaneous melanoma and to elucidate whether reverse transcriptase (RT)-PCR analysis of sentinel lymph nodes (SLNs) is valuable for predicting patient outcome. A total of 101 patients with primary cutaneous melanoma underwent SLNB at the Department of Dermatology, Kyushu University (Fukuoka, Japan), between May 2001 and December 2009. The removed nodes were stained with hematoxylin–eosin and with immunohistochemical stains for HMB-45, tyrosinase, MART-1, and MITF and multiple-mRNA marker (MART-1, tyrosinase, and GP-100) RT-PCR assays were conducted. The following clinicopathological variables were evaluated: age, sex, histological type, tumor site, Breslow thickness, disease-free survival (DFS), and melanoma-specific survival (MSS). Several parameters were analyzed for DFS and MSS using the Kaplan–Meier method and Cox proportional hazards model. The success rate of identifying SLNs was 98% (99 of 101 cases). Tumor-positive SLNs were significantly correlated with higher Breslow thickness, stage, tumor subtype, and tumor site. Patients with tumor-positive SLNs had a significantly shorter MSS and DFS than those with tumor-negative SLNs (P=0.0153 and 0.0004, respectively). Patients with at least two positive markers in the RT-PCR assay had a significantly shorter DFS than those with less than one marker (P=0.013). SLNB and multimarker RT-PCR analysis are useful for predicting the prognosis of patients with melanoma.

CD1a+, CD3+, CD4+, CD8+, CD68+ and cutaneous lymphocyte-associated antigen-positive cells in Bowen's disease

Background Bowen’s disease (BD) is a squamous cell carcinoma in situ that rarely invades into the underlying dermis. However, little is known about its immunohistology.

Pneumatosis Cystoides Intestinalis with Systemic Sclerosis, Limited Type Resulting in a Poor Prognosis

Pneumatosis cystoides intestinalis (PCI) is a rare disease characterized by the presence of multilocular intramural clusters of gas in the alimentary tract and has been considered to have a favorable response to conservative treatment. We describe the first case of limited type of systemic sclerosis (SSc) with PCI. A 74-year-old Japanese woman presented with a 4-month history of an unhealed cutaneous ulcer on the right third finger, along with sclerodactyly of bilateral hands. Proximal skin sclerosis was absent. The patient reported acute abdominal pain, and a diagnosis of PCI was established on plain radiography. The patient died of multiple organ failure 5 months after the development of PCI. PCI is rarely complicated with SSc, and all cases previously reported were associated with diffuse SSc. Because PCI is one of the poor prognostic factors of SSc, we should recognize the presence of this condition even in patients with limited cutaneous involvement.

Anti‐CXCR3 staining is useful for detecting human cutaneous and mucosal mast cells

Human synovial mast cells (MC) can be immunolabelled with antihuman CXCR3 antibody (Ab) (clone 49801). We have investigated whether cutaneous and mucosal MC are stained with anti‐CXCR3 Ab in paraffin‐embedded sections. Immunohistochemical staining and immunofluorescence double staining assays were performed with anti‐CXCR3, anti‐tryptase, and anti‐chymase Ab using normal skin, psoriatic skin lesions, and normal colon. When compared with tryptase and chymase staining, 100% of the cutaneous and 98% of the mucosal MC were positive for CXCR3. Anti‐CXCR3 staining is a useful marker for human cutaneous and mucosal MC in paraffin‐embedded sections.