Direct Inhibitory Effects of 17β-Estradiol on hCG-Stimulated cAMP and Testosterone Responses of Canine Testis

The direct effects of 17β-estradiol (E2) on testicular function were investigated using in situ perfusion of canine testis. During perfusion of E2 (10^-8-10^-4M), we measured the concentrations of cAMP, testosterone (T), androstenedione and 5α-dihydrotestosterone (DHT) in the spermatic venous effluent after hCG (500 IU) injection into the spermatic artery. The cAMP concentration in the spermatic venous effluent was 122 ± 3. 7 (SE) pmoles/ml, increasing after hCG to a peak level of 259.1 ± 33.0 (SE) pmoles/ml at 45 min and decreasing thereafter. T increased gradually from the pretreated level of 12.2 ± 4.4 (SE) mg/ml to 90.9 ± 30.9 (SE) ng/ml at 90 min after hCG injection. Androstenedione production was also stimulated by hCG. Although the pattern of changes of DHT in the venous effluent was similar to that of T, a statistical significant increase was not observed after hCG injection. Continuous infusion with E2 at the concentrations of 10^-8-^-4 M decreased hCG-induced cAMP increase in a dose-dependent fashion. The peak level of cAMP after hCG was shown to be increasingly depleted (50 and 80%) by the increasing doses of 10^-6 and 10^-4 M of exogenous E2. The responses of T and androstenedione were also suppressed by E2 and at 10^-4 M of E2 no increase was observed, although the response of cAMP to hCG remained. These findings indicate that E2 can directly suppress the hCG-stimulated steroidogenesis and cAMP production in in situ canine testis

Effects of Estrogen Treatment on the Responses of cAMP and Sex Steroids to hCG by the Testes of Patients with Prostatic Cancer

The effects of diethylstilbestrol diphosphate (DESDP) on testicular steroidogenesis were investigated in patients undergoing orchiectomy for prostatic carcinoma. In non-DESDP treated patients the concentration of cAMP in the spermatic venous blood was 17.8 ± 3.1 (SE) pmoles/ml, which increased to 343.3 ± 18.6 (SE) pmoles/ml 30 min after hCG (1,000 IU) injection into the testis. T increased gradually from the pretreated level of 26.5 ± 7.2 (SE) μg/dl at 50 min. A slight increase in DHT was observed after hCG injection. Ten days' injections of DESDP significantly reduced the responses of T and DHT to hCG and 20 days' injections decreased T and DHT responses as well as cAMP response to hCG. These findings indicate that DESDP can directly suppress the hCG stimulated steroidogenesis and cAMP production in human testis in vivo. The inhibitory effects of DESDP on Leydig cell function are probably on T biosynthesis as well as on cAMP formation

Risk factors for severity of colonic diverticular hemorrhage

Background/AimsColonic diverticular hemorrhage (DH) was a rare disease until the 1990s, and its incidence has increased rapidly since 2000 in Japan. In recent years, colonic DH has been the most frequent cause of lower gastrointestinal bleeding (LGIB). Nearly all cases of DH are mild, with the bleeding often stopping spontaneously. Some cases, however, require surgery or arterial embolization. In this study, using a cohort at Fukuoka University Chikushi Hospital, we investigated factors associated with severe colonic DH.MethodsAmong patients with LGIB who underwent colonoscopy at our hospital between 1995 and 2013, DH was identified in 273 patients. Among them, 62 patients (22.7%) were defined as having severe colonic DH according to recurrence of bleeding in a short period, and/or the necessity of transfusion, arterial embolization, or surgery. We then evaluated risk factors for severe DH among DH patients in this retrospective cohort.ResultsAmong the 273 patients with DH, use of non-steroidal anti-inflammatory drugs (NSAIDs) (odds ratio [OR], 2.801; 95% confidence interval [CI], 1.164–6.742), Charlson Risk Index (CRI) ≥2 (OR, 3.336; 95% CI, 1.154–7.353), right-sided colonic DH (OR, 3.873; 95% CI, 1.554–9.653), and symptoms of cerebral hypoperfusion (such as light-headedness, dizziness, or syncope) (OR, 2.926; 95% CI, 1.310–6.535) showed an increased risk of severe DH even after controlling for other factors.ConclusionsSevere DH occurred in 23% of DH patients, and NSAID use, CRI ≥2, right-sided colonic DH, and symptoms of cerebral hypoperfusion are suggested to be predictors of severe DH

Effects of Sub minimal Inhibitory Concentrations of Ampicillin on Hemagglutination of Escherichia coli

The hemagglutination (HA) activity of Escherichia coli was enhanced by subminimal inhibitory concentrations (sub-MICs) of ampicillin. One half of the MIC of ampicillin caused a bacterial filamentation and diminished bacterial piliation (as observed by light and electron microscopies) as well as an increase of HA activity. HA activity, however, decreased after separation of ampicillin-treated bacteria. These results indicate that the increase in HA activity by ampicillin is mainly due to filament formation

Validation of the 8th edition of the AJCC/UICC TNM staging system for tongue squamous cell carcinoma

Background: The revised 8th edition of the AJCC/UICC staging system was released in January 2017, and depth of invasion (DOI) was added to the new criteria for T classification in oral cavity cancer. In this study, we evaluated whether the 8th edition presents the prognosis and risk of nodal metastasis in patients with squamous cell carcinoma of tongue more accurately than did the 7th edition. Methods: The data for 112 patients were obtained and reclassified based on the criteria presented in the 8th edition. Results: Seven patients previously staged as T1 based on the criteria in the 7th edition were reclassified as T2 based on the 8th edition, while 19 T2 patients were reclassified as T3, and 9 T4a patients were reclassified as T3. T3 in the 8th edition represents a homogenous population showing the same prognosis, while T2 in the 8th edition represents a heterogenous population. Nodal metastasis was significantly correlated with T classification in both editions and DOI. However, neither the T classification in the 7th or 8th edition, nor DOI could predict the probability of potential nodal metastasis in patients with cN0 disease. Conclusions: The classification on T3 in the 8th edition can be seen as reasonable with regard to prognosis. Nodal metastasis was significantly correlated with T classification and DOI; however, the probability of subsequent nodal metastasis in patients with T2N0 was almost same for the criteria in the 7th and 8th editions, therefore, the same careful management as before is required for patients with N0 disease

Effect of Androgen and Aging on Ornithine Decarboxylase Activity of Rat Ventral Prostate

The age-related alteration of androgen dependency in ornithine decarboxylase (ODC) activity was examined in ventral prostate from: (1) intact rats aged 6, 10, 50 and 100W; (2) castrated rats aged 10 and 100W; (3) 10 and 100W rats castrated for 7 days before injection with testosterone propionate for up to 7 days. Tissue dihydrotestosterone (DHT) contents in ventral prostate from intact rats aged 10 and 100W were also measured. ODC activity of rat ventral prostate declined with aging. Castration resulted in rapid decline in ODC activity of young mature rats (l0W) and the activity was restored to normal value by the injection of testosterone propionate. On the other hand, the changes in ODC activity of old rats (100W) induced by castration and androgen replacement were significantly slower than those of young mature rats. In young mature rats, ODC activity was apparently correlated with prostatic DHT contents. Although prostatic DHT contents of old rats retained a similar level to young mature rats, no such correlation between ODC activity and tissue DHT content was observed. These results showed androgen-sensitive nature of ODC activity. And the sensitivity might be affected by aging at a step by which androgen showed its action

Expression of p53, p16, cyclin D1, EGFR and Notch1 in patients with the temporal bone squamous cell carcinoma

Background: The aim of this study was to investigate the expression of p53, p16, cyclin D1, epidermal growth factor receptor (EGFR) and Notch1 in temporal bone squamous cell carcinoma (TBSCC) tissue samples by immunohistochemistry (IHC), and to evaluate the association between these biomarkers and clinicopathological features. Methods: We performed a retrospective, single-institution review of 30 TBSCC patients treated with curative intent between April 2006 and March 2015. All tissue samples were obtained from pretreatment biopsy specimens or surgical specimens and using IHC staining. Results: Ten patients were categorized as T1, seven as T2, five as T3 and eight as T4. Nine patients had clinically positive lymph node metastasis. The positive expression of p53 and EGFR was significantly associated with T classification (P = 0.042 and P = 0.0039). EGFR expression was significantly more frequent in patients with positive lymph node metastasis compared with patients without node involvement (P = 0.017). In the analysis of the association between protein expression by IHC staining and prognosis, the positive expression of EGFR and Notch1 was significantly correlated with poor survival outcomes in TBSCC (P = 0.015 and P = 0.025) Conclusion: Overexpression of p53 and EGFR may be valuable biomarkers for identifying individuals at high risk of developing tumors in TBSCC. Furthermore, the positive expression of EGFR was significantly associated with poor survival outcome. Anti-EGFR therapy has potential for use as the treatment modality of choice for advanced-stage TBSCC as well as other head and neck squamous cell carcinomas

Genetic mutation analysis of the malignant transformation of sinonasal inverted papilloma by targeted amplicon sequencing

Background: The mechanism underlying the malignant transformation of inverted papilloma (IP) has not yet been elucidated. Methods: To clarify the genes responsible for the malignant transformation, we analyzed 10 cases of IP, 8 of IP with dysplasia, and 11 of squamous cell carcinoma (SCC) by targeted amplicon sequencing. Results: The number of mutant genes increased in the order of IP < dysplasia < SCC. Significant differences were observed in the mutation rates of three genes (KRAS, APC and STK11) in particular. TP53 was altered frequently in each group and might be involved in malignant transformation based on to the site of the mutation. A comparison of the genetic variants by region of IP tissue among patients with IP alone, and those with dysplasia or SCC revealed significant differences in the mutation rate of the KRAS gene. Conclusion: Identification of genetic mutations in KRAS is effective for predicting the malignant transformation of IP