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Germline mutations and copy number changes in DNA damage repair (DDR) genes such as BRCA2 are associated with aggressive forms of prostate cancer (PCa). Although the prevalence of BRCA2 variants in PCa is increasing in Japan, the genomic and biological implications in Japanese patients are unclear. An 81‐year‐old male presented with prostatic adenocarcinoma with neuroendocrine differentiation accompanied by metastatic lung nodule and brain metastases. Platinum‐based doublet chemotherapy combined with etoposide resulted in partial and complete remissions of brain and lung metastases, respectively. Next‐generation sequencing of biopsy and peripheral blood samples demonstrated a somatic BRCA2 mutation at c.7008‐2A>C and a germline mutation at p.E2877*. The patient's son had been diagnosed with breast cancer 2.5 years ago and was found to have the same germline BRCA2 mutation. BRCA2 mutation increases the risks of aggressive PCa and other cancer types in Japanese males. These forms may be highly responsive to platinum‐based chemotherapy. [ABSTRACT FROM AUTHOR]

Abstract: Objective: This study was designed to investigate the mechanism of salivary dysfunction in an experimental periodontitis rat model and to examine the improvements in salivary secretion following treatment of the experimental periodontitis. Methods: In the experimental periodontitis rat model, which included a unilateral ligature for 4 weeks around the second upper molar, several salivary functions were investigated. Changes in the salivary function were evaluated 4 weeks after removal of the ligature in some rats. Results: The periodontitis model showed significant reductions in the weight of the bilateral major salivary glands and pilocarpine-induced salivary secretion. The model also showed an increase in the number of apoptotic cells in bilateral salivary glands. According to Ca2+ imaging and Western blotting, there were no differences in the muscarine-induced intracellular Ca2+ mobilization in acinar cells or in the M3 receptor and AQP5 expression levels in the salivary glands between the sham and the periodontitis model. Following removal of the ligature, differences in the weights of salivary glands and pilocarpine-induced salivary secretion between the sham and the periodontitis model animals were not found. Conclusion: These results suggest that experimental periodontitis leads to hyposalivation and that relief from it improves salivary function. It is likely that lower levels of salivary secretion are caused by the decrease of functional acinar cells in salivary glands in the experimental periodontitis model, and the bilateral gland effects in the unilateral periodontitis model are caused by systemic rather than by local effects. [Copyright &y& Elsevier]

Oral Diseases (2012) 18, 568-574 Objective: To determine whether a link exists between inflammation and aquaporin-5 distribution in submandibular glands from three animal models for Sjögren's syndrome: IQI/JIC, r1ΔT/r2n and non-obese diabetic mice. Methods: Mice of different ages were used. Inflammatory infiltrates were quantified using the focus score. Acinar aquaporin-5 subcellular distribution was determined by immunohistochemistry and quantified using labelling indices. Results: Minor inflammatory infiltrates were present in r1f/r2n mice. Massive inflammatory infiltrates and acinar destruction were observed in 24-week-old non-obese diabetic mice, 10-and 13-month-old IQI/JIC mice and some r1ΔT/r2n mice. Aquaporin-5 immunoreactivity was primarily apical in submandibular glands from 8- and 24-week-old Balb/C mice, 8-week-old non-obese diabetic mice, 2-, 4- and 7-month-old IQI/JIC mice and r1f/r2n mice. In contrast, decreased apical aquaporin-5 labelling index with concomitant increased apical-basolateral, apical-cytoplasmic and/or apical-basolateral-cytoplasmic aquaporin-5 labelling indices was observed in 24-week-old non-obese diabetic, 10- and 13-month-old IQI/JIC and r1ΔT/r2n mice with a focus score ≥ 1. Conclusions: Altered aquaporin-5 distribution in submandibular acinar cells from IQI/JIC, non-obese diabetic and r1ΔT/r2n mice with a focus score ≥ 1 appears to be concomitant to the presence of inflammatory infiltrates and acinar destruction. [ABSTRACT FROM AUTHOR]

Aims: Our aim was to investigate plasma amino acid levels in chronic pancreatitis (CP) patients and examine their relationship with exocrine insufficiency. Methods: Thirty-nine patients with alcoholic CP and 20 healthy controls were examined. CP patients were divided into an exocrine normal group (n = 28) and an exocrine insufficiency group (n = 11). Selected clinical and laboratory values were compared among the three groups, and the effect of an elemental diet was observed in 6 patients of the exocrine insufficiency group. Results: Total amino acid concentration was significantly higher in the control group than in the exocrine normal group and exocrine insufficiency group (p = 0.032, p = 0.020). In the exocrine insufficiency group, significant reductions in the concentrations of serum histidine and methionine were found compared with the control group and exocrine normal group (histidine: p = 0.032, p = 0.045; methionine: p = 0.043, p = 0.049). In the exocrine normal group and exocrine insufficiency group, significant elevation in the concentration of serum glutamate was found compared with the control group (p = 0.036, p = 0.029). Elemental diet improved these amino acid concentrations. Conclusion: Patients with CP exhibit alterations in the levels of several amino acids, such as histidine, methionine, and glutamate. These amino acid deficiencies seem to correlate with exocrine insufficiency and be improved by an elemental diet. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]