Electrophysiological analysis of rhythmic jaw movements in the freely moving mouse

Although rhythmic jaw movement in feeding has been studied in mammals, such as rats, rabbits and monkeys, the cellular and molecular mechanisms underlying it are not well understood. Transgenic and gene-targeting technologies enable direct control of the genetic makeup of the mouse, and have led to the development of a new category of reagents that have the potential to elucidate the cellular and molecular mechanisms of neural networks. The present study attempts to characterize rhythmic jaw movements in the mouse and to demonstrate its relevance to rhythmic jaw movements found in higher mammals using newly developed jaw-tracking systems and electromyograms of the masticatory muscles. The masticatory sequence of the mouse during feeding was classified into two stages, incision and chewing. Small and rapid (8 Hz) open-close jaw movements were observed during incision, while large and slow (5 Hz) open-close jaw movements were observed during chewing. Integrated electromyograms of the masseteric and digastric muscles were larger during chewing than those observed during incision. Licking behavior was associated with regular (8 Hz), small open-close jaw movements with smaller masseteric activity than those observed during mastication. Grooming showed variable patterns of jaw movement and electromyograms depending on the grooming site. These results suggest that there are neuronal mechanisms producing different frequencies of rhythmic jaw movements in the mouse, and we conclude that the mouse is useful for understanding rhythmic jaw movements in higher mammals.     

Elevated expression of E-cadherin and α-, β-, and γ-catenins in metastatic lesions compared with primary epithelial ovarian carcinomas

E-cadherin and catenins play key roles in cell adhesion and motility. Little is known about the changes in expression of these molecules in the progression of ovarian carcinomas. In the present study, the immunohistochemical expression of E-cadherin and α-, β-, and γ-catenins was examined in 77 cases of ovarian carcinoma. In addition, the expression of these molecules was evaluated in 26 matched pairs of primary and metastatic lesions of advanced ovarian carcinomas. Of the 77 primary lesions, positive staining for E-cadherin and α-, β-, and γ-catenin was observed in 75 (97%), 63 (82%), 71 (92%) and 57 (74%) cases, respectively. Positivity for E-cadherin and α-, β-, and γ-catenin was significantly decreased in stage III and IV tumors compared with stage I and II tumors, suggesting that expression of the cadherin-catenin complex is reduced with the advancing stages of a tumor. Interestingly, expression of E-cadherin and α-, β-, and γ-catenin in the lesions of peritoneal dissemination was significantly increased compared with the primary lesions. These findings suggest that expression of the cadherin-catenin complex changes markedly and that reexpression may occur during the peritoneal dissemination of ovarian carcinoma cells.     

Adult Still's disease reflects a Th2 rather than a Th1 cytokine profile

Adult Still's disease (ASD) is a chronic multisystemic disease. Extraordinarily high serum levels of IL-18 in ASD patients have been described, whereas the mechanism remains to be clarified. This study aimed to evaluate proinflammatory cytokines and to consider their pathological roles. In patients with rheumatic diseases (n = 151), blood samples were taken at the active phase and the serum levels of IL-18 and other proinflammatory cytokines were measured by ELISA. The extra-high levels of IL-18 were confirmed selectively in ASD patients (n = 10). In the active phase of ASD patients, the levels of IL-6 were elevated accordingly, but IL-1beta and TNF-alpha were undetectable. As to Th1-Th2 cytokines, the levels of IL-4 and IL-13, but not INF-gamma, IL-12, or IL-2, were elevated in all ASD patients examined. Moreover, the serum levels of IL-18 showed a good correlation with those of IL-4, suggesting that ASD reflects a Th2 rather than a Th1 cytokine profile.     

Systemic administration of rIL-12 induces complete tumor regression and protective immunity: response is correlated with a striking reversal of suppressed IFN-{gamma} production by anti-tumor T cells

Unfractionated spleen cells taken from tumor-bearing mice 2weeks after tumor implantation contained tumor-primed T cellswhich produced cytokines including IL-2 and IFN- when culturedin vitro. With progressive tumor growth this initial lymphokine-producingcapacity decreased. Here, we investigated the ability of IL-12to (I) restore suppressed IFN- production, (II) cause tumorregression and (II) induce anti-tumor protective immunity. Additionof rIL-12 to spleen cell cultures from 4- to 10-week-old tumor-bearingmice resulted in a striking enhancement in the production ofIFN- compared with cultures of these cells in the absence ofrIL-12 or of normal spleen cells in the presence of rIL-12.Five I.p. injections of rIL-12 into mice bearing s.c. tumorsinduced complete tumor regression. This was found when rIL-12was given at early (1–2 weeks), intermediate (4–5weeks) or even late (7 weeks) stages of tumor growth. Furthermore,IL-12-treated mice which rejected the primary tumor exhibitedcomplete resistance to a rechallenge with the same tumor butdid not reject a second syngenetic tumor. Immunohistochemicalanalyses following IL-12 treatment revealed that CD4⁺ and CD8⁺T cells infiltrate the tumor. More importantly, IFN- mRNA expressionwas observed in fresh tumor masses from tumor-bearing mice receivingIL-12 treatment The importance of IFN- was further demonstratedby the observation that the systemic administration of anti-IFN-mAb prior to IL-12 treatment completely abrogated the anti-tumoreffect of IL-12. Thus, these results indicate that administrationof modest levels of rIL-12 to tumor-bearing mice results intumor regression through mechanisms involving reversal of suppressedIFN- production by anti-tumor T cells and the establishmentof a tumor-specific protective immune response.     

Overexpression of human thioredoxin in transgenic mice controls oxidative stress and life span

Transgenic (Tg) mice overexpressing human thioredoxin (TRX), a small redox-active protein, were produced to investigate the role of the protein in a variety of stresses. Bone marrow cells from TRX-Tg mice were more resistant to ultraviolet C-induced cytocide compared with those from wild type (WT) C57BL/6 mice. TRX-Tg mice exhibited extended median and maximum life spans compared with WT mice. Telomerase activity in spleen tissues in TRX-Tg mice was higher than that in WT mice. These results suggest that overexpression of TRX results in resistance against oxidative stress and a possible extension of life span without apparent abnormality in mammals.     

Adjuvant heparinization before manipulation of artery reduces early failure in primary arteriovenous fistula for end-stage renal disease patients

Clinical and Experimental Nephrology - Arteriovenous fistula (AVF) is the most preferred vascular access for hemodialysis patients, and early failure of AVF is one of the most avoidable...     

Therapeutic effects of the combined androgen blockade therapy versus luteinizing hormone-releasing hormone analog monotherapy in patients with hormone naïve metastatic prostate cancer: a multi-institutional comparative analysis

BackgroundThe clinical benefit of the combined androgen blockade (CAB) therapy over luteinizing hormone-releasing hormone analog (LH-RHa) monotherapy for hormone naïve metastatic prostate cancer (mHNPC) is unclear. Therefore, we retrospectively compare the effectiveness of CAB with the LH-RHa monotherapy on the prognosis of Japanese patients with mHNPC.MethodsWe retrospectively evaluated the prognosis of 517 patients diagnosed with mHNPC between August 2001 and May 2017. The patients’ data were obtained from the Michinoku Urological Cancer Research Group database and Hirosaki University-related hospitals. Patients were divided into the CAB and LH-RHa monotherapy groups based on primary androgen deprivation therapy (ADT). Overall survival (OS), cancer-specific survival (CSS), and castrate-resistant prostate cancer-free survival (CRPC-FS) were compared between the two groups using the Kaplan-Meier curve analysis. Inverse probability of treatment weighting (IPTW)-adjusted Cox hazard proportional analyses was performed to investigate the effect of primary ADT on oncological outcomes.ResultsThe median age was 73 years old. The numbers of patients in the CAB and LH-RHa monotherapy groups were 447 and 70, respectively. The Kaplan-Meier curve analysis showed no significant differences in either 5-year OS (56.7% vs. 52.5%, P=0.277), CSS (61.1% vs. 56.4%, P=0.400), and CRPC-FS (33.1% vs. 31.1%, P=0.529) between the groups. IPTW-adjusted multivariate Cox hazard proportional analyses showed no significant differences in OS, CSS, and CRPC-FS between the two groups.ConclusionsNo significant differences in oncological outcomes were observed between the CAB and LH-RHa monotherapy groups in patients with mHNPC.     

Primary anorectal malignant melanoma: Report of a case

(Received for publication on Aug. 18, 1997; accepted on May 15, 1998)     

Evaluation of a new solution containg trehalose for twenty-hour canine lung preservation

We examined the efficacy of two new preservation solutions containing trehalose-an extracellular type (ET-K) of solution and an intracellular type (IT-K) of solution — in relation to that of Euro-Collins (EC) solution in 20-h canine lung preservation. Canine lungs were flushed with one of the three solutions (n=5 for each solution) after pretreatment with PGE₁ (20 g/kg) and were stored for 20 h at 4°C. The left lungs were transplanted and evaluated to 6 h post transplant. In the ET-K group, the arterial oxygen tension after reperfusion was significantly higher than in the IT-K and EC groups. The pulmonary vascular resistance, wet/dry weight ratio, and histological evaluation of each transplanted lung in the ET-K group were also better than in the IT-K and EC groups. This indicates that ET-K solution is useful for 20-h preservation of canine lung grafts.     

Neck node metastasis after successful brachytherapy for early stage tongue carcinoma.

BACKGROUND AND PURPOSE: The accuracy of factors for predicting lymph node metastasis in patients with early-stage (stage I and II) mobile tongue carcinoma and prognostic factors associated with the clinical and pathological findings of lymph node metastasis were examined. MATERIAL AND METHODS: Between 1971 and 1998, 616 patients with early stage mobile tongue carcinoma were treated by brachytherapy with or without external irradiation. Neck lymph node metastasis occurred in a total of 237 cases, and 191 of them were not associated with primary failure. Neck dissection was performed in 169 of these 191 cases, and 16 cases were treated by radiotherapy. A pathological analysis was possible in 159 of the 169 neck dissection cases. RESULTS: There were 88 tongue cancer recurrences, and the incidence of neck metastasis was 38% (191/528) in the cases of primary controlled early tongue carcinoma, and 25% (38/151) and 41% (153/377), in stage-I and -II carcinoma, respectively. Neck metastasis was diagnosed within 12 months in 80% of cases, and within 24 months in 95%. Macroscopic appearance, tumor thickness and tumor length were identified as significant risk factors by a univariate analysis, but macroscopic appearance was the only significant risk factor identified by a multivariate analysis (P<0.001). The incidence of cervical lymph node metastasis was 62% among the invasive/ulcerative type tongue carcinomas, and was lower among the superficial type and exophytic/nodular type (20 and 35%, respectively). Regional and/or distant failure occurred in 75 of the 169 neck dissection cases (44%). The incidence of regional/distant failure was extremely high (49/68=72%) in the extra-nodal invasion group, and extra-nodal invasion was found even in small metastatic node less than 1 cm in length (20%). CONCLUSIONS: The macroscopic appearance of the primary tongue carcinoma has a major impact on the incidence of lymph node metastasis in patients with early tongue cancer, and extra-nodal invasion was the dominant risk factor for regional and distant failure. Treatment policy for clinically negative neck metastasis in early tongue cancer patients should be determined after considering the possibility of neck metastases and the morbidity associated with elective neck dissection.