Mutual effect of cerebral amyloid ß and peripheral lymphocytes in cognitively normal older individuals.

OBJECTIVE: We hypothesized that cerebral amyloid accumulation is reflected in the periphery in the pre-dementia stage and used flow cytometry to investigate the peripheral lymphocytes as an easily accessible biomarker to observe neuro-inflammation. We aimed to determine whether peripheral lymphocytes are related to the cortical amyloid burden or vice versa in cognitively normal older subjects. METHODS: We applied [11 C] Pittsburgh compound B (PiB)-positron emission tomography to 36 cognitively normal older individuals, and Aß deposition was quantified by cortical binding potential (PiB-BPND ). Blood samples were obtained, and lymphocyte subsets were evaluated. We examined differences between low and high PiB-BPND groups in the percentage of B cells, T cells, helper T cells, cytotoxic T cells, regulatory T cells, and natural killer cells. RESULTS: Subjects with high PiB-BPND showed significantly higher percentage of cytotoxic T cells (%CD3+ ). Correlation analysis revealed a significant relationship between the percentage of cytotoxic T cells and global cortical mean PiB-BPND . Hierarchical regression analyses showed that cytotoxic T cells were significantly related to the value of global cortical mean PiB-BPND and vice versa. CONCLUSIONS: Our results indicated that a specific peripheral immune response, reflected in the increased ratio of cytotoxic T cells, could be regarded as a preclinical sign of AD and could be attributed to the Aß neuropathological mechanism. Copyright © 2017 John Wiley & Sons, Ltd.

Histochemical localization of neutral proteases released during development of rat periradicular lesion.

OBJECTIVE: The purpose of the present study was to examine the role of various neutral proteases released during the development of periradicular lesion. DESIGN: This lesion produced by pulpal exposure of mandibular first molar in rat. The histological and histometrical changes in periapical tissue examined. The presence of neutrophil elastase, cathepsin G, collagenase 2, gelatinase B, and secretory leukocyte protease inhibitor (SLPI) was immunohistochemically evaluated in the periapical tissue. RESULTS: After pulpal exposure, some inflammatory cells were present in the periapical tissue at 7 days, and periapical inflammation gradually increased. Alveolar bone resorption observed after 14 days and apical abscess found after 21 days. After 14 days, the area of periradicular lesion significantly increased compared from normal one (p<0.05). Neutrophil elastase, cathepsin G, collagenase 2, and gelatinase B were detected around the root apex at 14 days, then these proteases increased gradually and demonstrated in and around the abscess at 21 and 28 days. Morphologically, these protease-expressing cells are almost polymorphic and polynuclear shaped after 14 days. These cells significantly increased after 14 days compared from normal one (p<0.05). However, SLPI detected after 21 days around apical root. It significantly increased after 21 days (p<0.05). CONCLUSIONS: These results suggested that neutrophil elastase, cathepsin G, collagenase 2, and gelatinase B induce the destruction of periapical tissue. We demonstrated that these neutral proteases released play an important role in development of periradicular lesion.

The expression of macrophage and neutrophil elastases in rat periradicular lesions.

Macrophage elastase and neutrophil elastase are involved in tissue destruction in periradicular lesions. The purpose of this study was to examine these elastases immunohistochemically during development of periradicular lesions induced in rat mandibular first molar by pulpal exposure for 7, 14, 21, 28, and 42 days. Histologically, periapical inflammation developed from 7 to 21 days and then subsided after 28 days. The area of these lesions gradually increased from 7 to 28 days and subsequently decreased at 42 days. Macrophage elastase was first detected at 7 days and predominantly shown from 14 to 28 days, whereas neutrophil elastase gradually increased from 14 to 28 days. Macrophage elastase was significantly greater than neutrophil elastase from 7 to 21 days. These results suggest that macrophage elastase was enhanced from an early stage during the development of these lesions and that neutrophil elastase was related to the expansion of periapical tissue destruction including bone resorption.

Increased number of anaerobic bacteria in the infected root canal in type 2 diabetic rats.

OBJECTIVE: The purpose of this study was to investigate the relationship between type 2 diabetes mellitus and anaerobic bacteria detected in infected root canals. STUDY DESIGN: Normal Wistar rats (control) received a standard laboratory diet with water (group A), and GK rats (type 2 diabetes mellitus rats) a normal laboratory diet with water (group B) or a 30% sucrose solution (group C). Chemotaxis assay was conducted on polymorphonuclear leukocytes from the 3 groups, and the numbers of anaerobic bacteria in infected root canals were determined. RESULTS: In the chemotaxis assay on the polymorphonuclear leukocytes, the chemotactic response of cells in group C was lower than that for groups A and B (P < .01). As to bacteria detected in the root canal, obligate anaerobic bacteria which stained gram negative, were significantly more numerous in group C (P < .01) than in groups A and B. CONCLUSION: The metabolic condition produced by type 2 diabetes mellitus in rats might lower the general host resistance against bacterial infection.

Role of IL-2 and helper T-lymphocytes in limiting periapical pathosis.

The purpose of this study was to examine the role of IL-2 and helper T-lymphocytes in the development of periradicular lesions in rats. In control animals, periradicular lesions developed within 28 days following pulpal infection. Immunologically, some anti IL-2 and anti CD4-reactive helper T-lymphocytes infiltrated the periapical tissue at 14 days, and their numbers increased at 28 days. In experimental animals, tacrolimus (FK506) was injected every day to inhibit the IL-2 production by helper T-cells. Histologically, the pulpal necrosis and periradicular inflammation in tacrolimus-treated rats were more severe than those in the control rats. Furthermore, the areas of pulpal necrosis and periradicular lesion in the immunosuppressed rat were significantly greater than those in the normal ones. The numbers of IL-2- and CD4-positive cells in the lesion of the experimental rats were statistically lower than those of the control ones. These results show that the decrease in IL-2 might have promoted the development of periradicular lesions.

Adenocarcinoma arising from a mature cystic teratoma of the testis.

A 52-year-old male diagnosed pathologically with metastatic adenocarcinoma of the skin was referred to our department. Physical examination revealed a right scrotal mass the size of child's head and several skin tumors. Right high orchiectomy and resection of skin tumors were performed. Histopathological examination revealed a well-differentiated, mucinous adenocarcinoma originating from the gastrointestinal epithelium in a mature cystic teratoma (dermoid cyst) of the testis and metastatic mucinous adenocarcinoma of the skin. We made a diagnosis of teratoma with malignant transformation (TMT) of the testis. Combination chemotherapy with low-dose cisplatin/5'-deoxy-5-fluorouridine (CDDP/5'-DFUR) was initiated, but the patient died 8 months after orchiectomy. At autopsy, similar mucinous adenocarcinoma of the testis and the skin were observed at the metastatic sites.

Proliferating cell nuclear antigen in testes of infertile men with varicocele--preliminary results of interrelationship with sperm count before and after varicocelectomy.

OBJECTIVE: This study was conducted to assess germ cell kinetics and correlate them with sperm counts before and after varicocelectomy. MATERIAL AND METHODS: Forty-three testicular biopsy specimens were obtained from 47 patients with varicocele during varicocelectomy. Similar specimens were obtained from 8 fertile volunteers. All specimens were immunostained using anti-proliferating cell nuclear antigen (anti-PCNA) antibody. PCNA expression was evaluated by assessing its staining intensity (SI) and labeling index (LI). RESULTS: The varicocele specimens revealed significantly lower SI and LI than the controls. There was a significant correlation between initial sperm concentration and LI but not SI. Coexistence of LI > or = 31 and preoperative sperm count > 1 million/ml correlated with a significant rise in the postoperative sperm count. CONCLUSIONS: PCNA is a useful molecular marker for assessing germ cell kinetics in varicocele patients. The decline in DNA synthesis, as suggested by the lower PCNA SI and LI in varicocele specimens, could be a reason for the disordered spermatogenesis in these patients. PCNA LI may also be considered as a beneficial clinical marker and may help to predict the surgical outcome after varicocele repair.