Bisphenol a accelerates terminal differentiation of 3T3-L1 cells into adipocytes through the phosphatidylinositol 3-kinase pathway.

In order to identify whether bisphenol A (BPA) acts as an adipogenic agent, following the hormonal induction of differentiation into adipocytes, 3T3-L1 cells were treated for six days with BPA alone. Treatment with BPA increased the triacylglycerol (TG) content of the cultures, increased the percentage of Oil Red O-staining cells in the cultures, and increased the levels of lipoprotein lipase (LPL) and adipocyte-specific fatty acid binding protein (aP2) mRNAs. These findings indicate that BPA was able to accelerate terminal differentiation of 3T3-L1 cells into adipocytes. LY294002, a chemical inhibitor of phosphatidylinositol 3-kinase (PI 3-kinase), blocked completely the increasing effect of BPA on TG accumulation and expression of LPL and aP2 mRNAs. Western blot analysis revealed that BPA increased the level of phosphorylated Akt kinase. Based on these findings, we concluded that BPA acted through the PI 3-kinase and Akt kinase pathway, resulting in increased TG accumulation and expression of adipocyte genes. The structure-activity relationship for BPA-related chemicals was examined. Eight derivatives of BPA (three diphenylalkanes with different substituents at the central carbon atom, three diphenylalkanes with ester bonds on hydroxyl groups in the phenolic rings, one bisphenol consisting of a sulphur atom at the central position, one chemical with cyanic groups, instead of hydroxyl groups, in the phenolic rings) accelerated terminal adipocyte differentiation and their potencies to increase TG accumulation were 73-97% of that of BPA. Two diphenylalkanes with ether bonds on hydroxyl groups and two alkylphenols (4-nonylphenol and 4-tert-octylphenol) did not have the ability to accelerate terminal adipocyte differentiation.     

Two Japanese cases of dermatitis herpetiformis associated each with lung cancer and autoimmune pancreatitis but showing no intestinal symptom or circulating immunoglobulin A antibodies to any known antigens

Dermatitis herpetiformis (DH) is common in some Caucasian populations but extremely rare in Japanese, probably because of different immunogenetic backgrounds. We report two Japanese DH cases with typical clinical, histological and direct immunofluorescence features. However, no symptom of gluten‐sensitive enteropathy was shown. The diagnosis was confirmed by eliminating other autoimmune blistering diseases by indirect immunofluorescence, enzyme‐linked immunosorbent assays and immunoblotting. However, circulating immunoglobulin (Ig)A anti‐endomysium, reticulin and gliadin antibodies were not detected. IgA antibodies to tissue and epidermal transglutaminases were also negative. One case was associated with lung cancer and the other one with autoimmune pancreatitis. On review of 17 cases of DH reported in Japan over the previous 10 years, including our cases, one case was associated with gluten‐sensitive enteropathy, four with malignant neoplasms, two with autoimmune systemic disorders and one with psoriasis. Although our cases were typical of DH in clinical, histopathological and IgA deposit features, they showed different human leukocyte antigen haplotypes, no gluten‐sensitive enteropathy and no DH‐specific IgA antibodies, including those to epidermal and tissue transglutaminases. These results suggest that studies of unique characteristics in Japanese DH patients should facilitate further understanding of pathogenesis in DH.     

Palmoplantar keratosis in oculodentodigital dysplasia with a GJA1 point mutation out of the C‐terminal region of connexin 43

Gap junction proteins are composed of 21 genes of the connexin (Cx) family. They play important roles in cell–cell contact by exchange of small molecules through hemichannels. Hence, mutations of Cx family genes affect various tissues of a body. The mutation of the GJA1 gene, which codes Cx43, causes oculodentodigital dysplasia (ODDD), commonly in an autosomal dominant manner with phenotypic variability. It has been believed that gene mutations causing truncation of the Cx43 C‐terminus is necessary and sufficient for palmoplantar keratosis (PPK) development in ODDD patients. Here, we report a case of an ODDD patient developing PPK with a GJA1 gene mutation (c.412G>A/p.Gly138Ser), which was previously reported in a case of ODDD without PPK and expected not to result in C‐terminal truncation of Cx43. This case suggests not only C‐terminal truncation, but also that a point mutation in the cytoplasmic region of Cx43 can cause PPK in ODDD patients.     

Comparison between famciclovir and valacyclovir for acute pain in adult Japanese immunocompetent patients with herpes zoster

Famciclovir is a guanine analog antiviral drug used commonly for herpes zoster. Efficacy of famciclovir treatment has been reported to be comparable to valacyclovir treatment. Both of these medications reduce the time to complete cessation of zoster‐associated pain including post‐herpetic neuralgia, as compared to acyclovir. We conducted a multicenter, randomized, open clinical trial in order to evaluate the extent of pain relief afforded by these two antiviral drugs during the acute disease phase of herpes zoster. The study group comprised 86 immunocompetent adult patients suffering from herpes zoster, who were treated with either famciclovir or valacyclovir for 7 days. Of these, 55 patients enrolled in this study within 72 h of the onset of the rash and 31 patients after 72 h of the onset. There was a significant reduction in acute herpes zoster pain with famciclovir on day 7 and at 2–3 weeks in both of these patient groups, while with valacyclovir, there was not significant reduction in pain on day 7. Of patients aged 50 years or older, there was a significantly earlier reduction in pain with famciclovir than with valacyclovir. In addition, a significant reduction in the number of patients with pain was observed as early as days 3–4 with famciclovir treatment as compared with valacyclovir treatment. We conclude that famciclovir was superior to valacyclovir in the relief of acute pain of herpes zoster. Accordingly, famciclovir is recommended for herpes zoster patients with moderate symptoms and a visual analog scale score of under 50 mm.     

A case of malignant thymoma mimicking thyroid carcinoma: a pitfall in fine-needle aspiration

A case of malignant thymoma presenting as an anterior neck mass is reported. The tumor extended from the thyroid gland to the superior mediastinum. It did not accumulate Tc-99m pertechnetate, but continued to accumulate Tl-201 at the late phase. A fine-needle aspiration cytology from the tumor showed tight clusters of epithelial cells with crowded ovoid nuclei. The tumor was initially diagnosed as thyroid carcinoma, clinically and cytologically. A thymoma with a dominant epithelial component has to be considered in the differential diagnosis of a suspected papillary carcinoma of the thyroid.     

Definitive radiotherapy for primary vaginal cancer: correlation between treatment patterns and recurrence rate

The purpose of this study was to determine the outcomes and optimal practice patterns of definitive radiotherapy for primary vaginal cancer. Between 1993 and 2012, 49 patients were treated with definitive radiotherapy for primary vaginal cancer in three hospitals. Of these, 15 patients (31%) had clinically positive regional lymph node metastasis. A total of 34 patients (70%) received external beam radiotherapy with high-dose-rate brachytherapy (interstitial or intracavitary), and 8 (16%) (with small superficial Stage I tumors) were treated with local radiotherapy. The median follow-up was 33 months (range: 1–169 months). The 3-year overall survival (OS), disease-free survival (DFS), and loco-regional control (LRC) rates were 83%, 59% and 71%, respectively. In multivariate analysis, the histological type (P = 0.044) was significant risk factors for LRC. In Federation of Gynecology and Obstetrics (FIGO) Stage I cases, 3 of 8 patients (38%) who did not undergo prophylactic lymph node irradiation had lymph node recurrence, compared with 2 of 12 patients (17%) who underwent prophylactic pelvic irradiation. For Stage III–IV tumors, the local recurrence rate was 50% and the lymph node recurrence rate was 40%. Patients with FIGO Stage I/II or clinical Stage N1 had a higher recurrence rate with treatment using a single modality compared with the recurrence rate using combined modalities. In conclusion, our treatment outcomes for vaginal cancer were acceptable, but external beam radiotherapy with brachytherapy (interstitial or intracavitary) was needed regardless of FIGO stage. Improvement of treatment outcomes in cases of FIGO Stage III or IV remains a significant challenge.     

CD13/aminopeptidase N in collagen vascular diseases

To determine the significance of CD13/aminopeptidase N in collagen vascular diseases (CVD), we examined its activity and expression in sera and disease sites of patients with CVD. Significantly higher aminopeptidase activity was detected in bronchoalveolar lavage fluid from patients with interstitial lung diseases due to rheumatoid arthritis (RA), polymyositis/dermatomyositis (PM/DM), systemic sclerosis (SSc), and Sjögren's syndrome than from control subjects. Increased aminopeptidase activity and increased expression of CD13/aminopeptidase N protein were found in alveolar macrophages from CVD patients with interstitial lung diseases. Significantly higher aminopeptidase activity was detected in pleural effusions from patients with systemic lupus erythematosus (SLE) than in transudate effusions. The mean aminopeptidase activity in synovial fluids from RA patients was significantly higher than from patients with osteoarthritis. The mean value of serum aminopeptidase activity was significantly higher in patients with SLE, RA, SSc, and PM/DM than in normal subjects. This study suggests that the activity of CD13/aminopeptidase N, locally produced in the disease site, is a useful marker for CVD and that CD13/aminopeptidase N may have an important role in the pathogenesis of CVD.