A C/T polymorphism in the 5' untranslated region of the CD40 gene is associated with later onset of Graves' disease in Japanese

Graves' disease (GD) is an autoimmune disorder with genetic predisposition. CD40, which stimulates lymphocyte proliferation and differentiation, is an important immunomodulator and is expressed in the thyroid follicular cells as well as antigen-presenting cells. A single nucleotide polymorphism (SNP) at position -1 of the Kozak sequence of the CD40 gene has been reported to be associated with the development of GD. The aim of the present study was to investigate whether CD40 gene polymorphism confers susceptibility to GD in Japanese. CD40 gene polymorphisms were studied in Japanese GD patients (n = 324) and healthy control subjects without anti-thyroid autoantibodies or a family history of autoimmune disorders (n = 229). A C/T polymorphism at position -1 of the CD40 gene was measured using the polymerase chain reaction restriction fragment length polymorphism. There was no significant difference in allele or genotype frequency of the CD40 SNP between GD and control subjects. There was a significant decrease in the TT genotype frequency in the GD patients, who developed GD after 40 years old, than those under 40 year of age. These data suggest that the SNP of CD40 gene is associated with susceptibility to later onset of GD in Japanese.     

Effects of tadalafil on storage and voiding function in patients with male lower urinary tract symptoms suggestive of benign prostatic hyperplasia: A urodynamic‐based study

Objective

To investigate the effects of tadalafil on storage and voiding function in treatment‐naïve patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia, based on a urodynamic study.

Methods

This was an open‐labeled, single‐center, prospective study. A total of 80 untreated outpatients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia received tadalafil 5 mg/day for 12 weeks. Subjective symptoms and objective findings on voiding and storage function obtained through urodynamic studies, including cystometry and pressure flow study, were evaluated before and after treatment.

Results

A total of 71 patients with a mean age of 70.2 years and a mean prostate volume of 45.6 mL were included in the analysis. In the International Prostate Symptom Score and Overactive Bladder Symptom Score, mean total scores significantly improved from 18.2 to 13.4 (P < 0.001) and 6.5 to 4.7 (P < 0.001), respectively, after treatment. Mean maximum bladder capacity significantly increased by approximately 35 mL (P < 0.001). Detrusor overactivity disappeared in 15 (39.5%) of 38 patients with detrusor overactivity at baseline (P < 0.001). Mean maximum flow rate on pressure flow study significantly increased from 7.1 to 9.1 mL/s (P < 0.001) and mean bladder outlet obstruction index significantly decreased from 61.3 to 47.1 (P < 0.001).

Conclusions

Treatment with tadalafil 5 mg once daily effectively relieves lower urinary tract symptoms based on objective improvement of storage and voiding function, such as detrusor overactivity and bladder outlet obstruction, in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.     

Mechanical forces induce odontoblastic differentiation of mesenchymal stem cells on three‐dimensional biomimetic scaffolds

The mechanical induction of cell differentiation is well known. However, the effect of mechanical compression on odontoblastic differentiation remains to be elucidated. Thus, we first determined the optimal conditions for the induction of human dental pulp stem cells (hDPSCs) into odontoblastic differentiation in response to mechanical compression of three‐dimensional (3D) scaffolds with dentinal tubule‐like pores. The odontoblastic differentiation was evaluated by gene expression and confocal laser microscopy. The optimal conditions, which were: cell density, 4.0 × 10⁵ cells/cm²; compression magnitude, 19.6 kPa; and loading time, 9 h, significantly increased expression of the odontoblast‐specific markers dentine sialophosphoprotein (DSPP) and enamelysin and enhanced the elongation of cellular processes into the pores of the membrane, a typical morphological feature of odontoblasts. In addition, upregulation of bone morphogenetic protein 7 (BMP7) and wingless‐type MMTV integration site family member 10a (Wnt10a) was observed. Moreover, the phosphorylation levels of mitogen‐activated protein kinases (MAPKs), extracellular signal‐regulated kinase 1/2 (ERK1/2) and p38 were also enhanced by mechanical compression, indicating the involvement of the MAPK signalling pathway. It is noteworthy that human mesenchymal stem cells (MSCs) derived from bone marrow and amnion also differentiated into odontoblasts in response to the optimal mechanical compression, demonstrating the importance of the physical structure of the scaffold in odontoblastic differentiation. Thus, odontoblastic differentiation of hDPSCs is promoted by optimal mechanical compression through the MAPK signalling pathway and expression of the BMP7 and Wnt10a genes. The 3D biomimetic scaffolds with dentinal tubule‐like pores were critical for the odontoblastic differentiation of MSCs induced by mechanical compression. Copyright © 2014 John Wiley & Sons, Ltd.     

Evaluation of 11C-choline PET/CT for primary diagnosis and staging of urothelial carcinoma of the upper urinary tract: a pilot study

Purpose

We conducted a pilot study to prospectively evaluate the efficacy of PET/CT with ¹¹C-choline (choline PET/CT) for primary diagnosis and staging of urothelial carcinoma of the upper urinary tract (UUT-UC).

Methods

Enrolled in this study were 16 patients (9 men, 7 women; age range 51 – 83 years, mean?±?SD 69?±?10.8 years) with suspected UUT-UC. The patients were examined by choline PET/CT, and 13 underwent laparoscopic nephroureterectomy and partial cystectomy. Lymphadenectomy and chemotherapy were also performed as necessary in some of the patients. Of the 16 patients, 12 were confirmed to have UUT-UC (7 renal pelvis carcinoma and 5 ureteral carcinoma), 1 had malignant lymphoma (ureter), 1 had IgG4-related disease (ureter), and 2 had other benign diseases (ureter).

Results

Of the 16 study patients, 13 showed definite choline uptake in urothelial lesions, and of these, 11 had UUT-UC, 1 had malignant lymphoma, and 1 had IgG4-related disease. Three patients without choline uptake comprised one with UUT-UC and two with benign diseases. Of the 12 patients with UUT-UC, 3 had distant metastases, 2 had metastases only in the regional lymph nodes, and 7 had no metastases. Distant metastases and metastases in the regional lymph nodes showed definite choline uptake. The outcome in patients with UUT-UC, which was evaluated 592 – 1,530 days after surgery, corresponded to the patient classification based on the presence or absence of metastases and locoregional or distant metastases. Choline uptake determined as SUVmax 10 min after administration was significantly higher than at 20 min in metastatic tumours of UUT-UC (p?Conclusion This study suggests that choline PET/CT is a promising tool for the primary diagnosis and staging of UUT-UC.     

The oligodendroglial histological features are not independently predictive of patient prognosis in lower-grade gliomas

Brain Tumor Pathology - The relevance of oligodendroglial histological features to patient prognoses is controversial. 93 LrGGs resected for about 2 decades were re-assessed based on WHO2007 with...     

Increased urethral resistance by periurethral injection of low serum cultured adipose‐derived mesenchymal stromal cells in rats

Objectives: To evaluate the effects of a periurethral injection of low serum cultured adipose tissue‐derived mesenchymal stromal cells (LASC) and to develop a new autologous cell therapy for stress urinary incontinence. Methods: F344 rats were divided into three groups as based on the periurethral injection of LASC, GAX collagen or vehicle (control). At 2 and 4 weeks after injection, leak point pressure (LPP) was measured before and after transection of the pelvic nerves. For cell tracking, LASC of green fluorescent protein transgenic rats were injected into nude rats. Results: At 2 weeks, both the LASC and collagen groups showed significantly higher LPP than the control group. At 4 weeks, the increase in LPP in the LASC group remained, whereas LPP in the collagen group decreased to baseline levels. In the absence of the urethral closure reflex after transection of the pelvic nerves, LPP in the LASC group was significantly higher than that in the other two groups. Histologically, the size of the urethral lumen was smaller in the LASC group than the collagen group. At 4 weeks, most of the LASC were positive for myogenic antigens including α‐smooth muscle actin, desmin and calponin I. Conclusions: Periurethral injection of autologous LASC capable of myogenic differentiation made a greater contribution to the increase in urethral resistance than did the conventional collagen bulk injection. Thus, its use for treatment of stress urinary incontinence can be postulated.     

Case report of malignant sertoli cell tumor

Malignant sertoli cell tumor is a rare disease and only a few cases have been described previously. We report a terminal case of malignant sertoli cell tumor. A 38-year-old male visited a hospital with a complaint of swelling his left testis. He underwent high left orchiectomy. His pathologic diagnosis was suspected seminoma, and all tumor markers (LDH, HCG, AFP) were negative, and CT imaging confirmed clinical stage 1 (pT1N0M0S0). One year later, a CT scan showed a small retroperitoneum lymph node swelling. Four months later, these lesions increased to 55 x 45 x 70 mm in diameter. He received 3 courses of chemotherapy with BEP (bleomycine, etoposide, cisplatin), but, lymph node size did not change. After he underwent a CT guided lymph node biopsy, his pathologic diagnosis was viable embryonal carcinoma. He then came to our hospital. We selected CPT-11 and nedaplatin for his salvage chemotherapy, but lymph node lesions did not change. After he received 3 courses of chemotherapy, we performed retroperitoneal lymphadenectomy. His pathologic diagnosis was viable sertoli cell tumor, malignant type. After 30 days, he had multiple liver metastases ane died 27 months after orchiectomy. All tumor markers were negative in his all clinical courses.