Effects of Testosterone Replacement on Lower Urinary Tract Functions in Elderly Male Rats

Testosterone has been clinically used to improve hormone deficiency in the aging male; however, investigations how testosterone exerts its effects on lower urinary tract functions are not many. In order to shed light on the efficacy of testosterone on the functions, we replaced teststerone in elderly male Wistar rats aged 19 months. A relevant dose (120 mg) of testosterone was subcutaneously replaced through an implanted silastic tube into 6 rats for 4 weeks (treated group). Another 6 rats received no treatment for 4 weeks (control group). After the end of the 4-week period, we measured plasma testesterone, weight of bladder, prostate and body, bladder muscle content, spontaneous micturition behavior and cystometric parameters, and compared the results between the 2 groups. The daily micturition frequency (18.8 ± 1.5 times/day versus 15.5 ± 1.9 times/day), volume of residual urine at cystometry (0.66 ± 0.10 mL versus 0.24 ± 0.03 mL), bladder capacity (1.03 ± 0.06 mL versus 0.65 ± 0.05 mL), bladder weight (258 ± 9 mg versus 198 ± 19 mg), prostate weight (2.08 ± 0.22 g versus 1.29 ± 0.22 g) and ratio of smooth muscle area/connective tissue area (3.59 ± 0.13 versus 2.59 ± 0.36) were significantly higher in the treated group (P < 0.05). In contrast, the average volume of spontaneous micturition was significantly lower in the treated group (0.84 ± 0.07 mL versus 0.98 ± 0.09 mL). Differences in body weight and volume of 24-h urine were not significant between groups. Daily micturition frequency and volume of residual urine at cystometry were increased in the treated group. Testosterone replacement exerted unfavorable effects on the lower urinary functions of elderly rats, including prostatic hypertrophy

Indigenous utilization of termite mounds and their sustainability in a rice growing village of the central plain of Laos

<p>Abstract</p> <p>Background</p> <p>The objective of this study was to investigate the indigenous utilization of termite mounds and termites in a rain-fed rice growing village in the central plain of Laos, where rice production is low and varies year-to-year, and to assess the possibility of sustainable termite mound utilization in the future. This research was carried out from 2007 to 2009.</p> <p>Methods</p> <p>The termites were collected from their mounds and surrounding areas and identified. Twenty villagers were interviewed on their use of termites and their mounds in the village. Sixty-three mounds were measured to determine their dimensions in early March, early July and middle to late November, 2009.</p> <p>Results</p> <p>Eleven species of Termitidae were recorded during the survey period. It was found that the villagers use termite mounds as fertilizer for growing rice, vegetable beds and charcoal kilns. The villagers collected termites for food and as feed for breeding fish. Over the survey period, 81% of the mounds surveyed increased in volume; however, the volume was estimated to decrease by 0.114 m³mound^-1year^-1on average due to several mounds being completely cut out.</p> <p>Conclusion</p> <p>It was concluded that current mound utilization by villagers is not sustainable. To ensure sustainable termite utilization in the future, studies should be conducted to enhance factors that promote mound restoration by termites. Furthermore, it will be necessary to improve mound conservation methods used by the villagers after changes in the soil mass of mounds in paddy fields and forests has been measured accurately. The socio-economic factors that affect mound utilization should also be studied.</p

Essential role of gastric gland mucin in preventing gastric cancer in mice

信州大学博士（医学）・学位論文・平成24年3月31日授与（甲第916号）・唐澤文寿Gastric gland mucin secreted from the lower portion of the gastric mucosa contains unique O-linked oligosaccharides (O-glycans) having terminal alpha 1,4-linked N-acetylglucosamine residues (alpha GlcNAc). Previously, we identified human alpha 1,4-N-acetylglucosaminyltransferase (alpha 4GnT), which is responsible for the O-glycan biosynthesis and characterized alpha GlcNAc function in suppressing Helicobacter pylori in vitro. In the present study, we engineered A4gnt(-/-) mice to better understand its role in vivo. A4gnt(-/-) mice showed complete lack of alpha GlcNAc expression in gastric gland mucin. Surprisingly, all the mutant mice developed gastric adenocarcinoma through a hyperplasia-dysplasia-carcinoma sequence in the absence of H. pylori infection. Microarray and quantitative RT-PCR analysis revealed upregulation of genes encoding inflammatory chemokine ligands, proinflammatory cytokines, and growth factors, such as Ccl2, Il-11, and Hgf in the gastric mucosa of A4gnt(-/-) mice. Further supporting an important role for this O-glycan in cancer progression, we also observed significantly reduced alpha GlcNAc in human gastric adenocarcinoma and adenoma. Our results demonstrate that the absence of alpha GlcNAc triggers gastric tumorigenesis through inflammation-associated pathways in vivo. Thus, alpha GlcNAc-terminated gastric mucin plays dual roles in preventing gastric cancer by inhibiting H. pylori infection and also suppressing tumor-promoting inflammation.ArticleJOURNAL OF CLINICAL INVESTIGATION. 122(3):923-934 (2012)journal articl

Recombinant human FGF-2 for the treatment of early-stage osteonecrosis of the femoral head: TRION, a single-arm, multicenter, Phase II trial

Aim: This study aimed to evaluate the 2-year outcomes from a clinical trial of recombinant human FGF-2 (rhFGF-2) for osteonecrosis of the femoral head (ONFH). Patients & methods: Sixty-four patients with nontraumatic, precollapse and large ONFHs were percutaneously administered with 800 μg rhFGF-2 contained in gelatin hydrogel. Setting the end point of radiological collapse, we analyzed the joint preservation period of the historical control. Changes in two validated clinical scores, bone regeneration and safety were evaluated. Results: Radiological joint preservation time was significantly higher in the rhFGF-2 group than in the control group. The ONFHs tended to improve to smaller ONFHs. The postoperative clinical scores significantly improved. Thirteen serious adverse events showed recovery. Conclusion: rhFGF-2 treatment increases joint preservation time with clinical efficacy, radiological bone regeneration and safety

[23-1]English Summaries of the Papers Contributed to Tonan Ajia Kenkyu (The Southeast Asian Studies) Vol.23, No.3 (Special Issue for Don Daeng : An Integrated Village Study in Northeast Thailand)

Tonan Ajia Kenkyu (The Southeast Asian Studies) = 東南アジア研究 (Japanese Journal of Southeast Asian Studies)[1]EDITOR'S NOTE … Hayao FUKUI[2]A Brief Look at the Village … Yoshihiro Kaida, Masuo Kuchiba[3]Typology of Rice Cultivation … Shuichi MIYAGAWA, Toshiro KURODA, Hiroyuki MATSUFUJI, Tomoo HATTORI[4]Instability of Rice culture … Yoshihiro KAIDA, Kazutoshi HOSHIKAWA, Yasuyuki KOHNO[5]POPULATION (I) … Hayao FUKUI[6]The Process of Emigration in Search of Good Land to Mo Nua Village, Udonthani Province … Yukio HAYASHI[7]An Economic Analysis of Endogenous Rural Economic Evolution and its Policy Implications … Hiroshi Tsujii[8]Kin Relationships and Kin Cooperation for Farming and Consumption … Masuo KUCHIBA, Takahiro TAKEMURA[9]Daily Activity Survey (1) … Satoshi KOIKE, Shinji SUWA, Haruo NOMA[10]Sharing of Merit and the Associated Social Relationships of Funeral Rites … Yukio HAYASHI[11]AN OVERVIEW ON NATURE, AGRICULTURE AND ECONOMY … Hayao FUKU

Collagen adhesion gene is associated with blood stream infections caused by methicillin-resistant Staphylococcus aureus

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) causes hospital- and community-acquired infections. It is not clear whether genetic characteristics of the bacteria contribute to disease pathogenesis in MRSA infection. We hypothesized that whole genome analysis of MRSA strains could reveal the key gene loci and/or the gene mutations that affect clinical manifestations of MRSA infection. Methods: Whole genome sequences (WGS) of MRSA of 154 strains were analyzed with respect to clinical manifestations and data. Further, we evaluated the association between clinical manifestations in MRSA infection and genomic information. Results: WGS revealed gene mutations that correlated with clinical manifestations of MRSA infection. Moreover, 12 mutations were selected as important mutations by Random Forest analysis. Cluster analysis revealed strains associated with a high frequency of bloodstream infection (BSI). Twenty seven out of 34 strains in this cluster caused BSI. These strains were all positive for collagen adhesion gene (cna) and have mutations in the locus, those were selected by Random Forest analysis. Univariate and multivariate analysis revealed that these gene mutations were the predictor for the incidence of BSI. Interestingly, mutant CNA protein showed lower attachment ability to collagen, suggesting that the mutant protein might contribute to the dissemination of bacteria. Conclusions: These findings suggest that the bacterial genotype affects the clinical characteristics of MRSA infection. (c) 2019 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases

Genome-Wide Association Study Confirming Association of HLA-DP with Protection against Chronic Hepatitis B and Viral Clearance in Japanese and Korean

Hepatitis B virus (HBV) infection can lead to serious liver diseases, including liver cirrhosis (LC) and hepatocellular carcinoma (HCC); however, about 85–90% of infected individuals become inactive carriers with sustained biochemical remission and very low risk of LC or HCC. To identify host genetic factors contributing to HBV clearance, we conducted genome-wide association studies (GWAS) and replication analysis using samples from HBV carriers and spontaneously HBV-resolved Japanese and Korean individuals. Association analysis in the Japanese and Korean data identified the HLA-DPA1 and HLA-DPB1 genes with Pmeta = 1.89×10−12 for rs3077 and Pmeta = 9.69×10−10 for rs9277542. We also found that the HLA-DPA1 and HLA-DPB1 genes were significantly associated with protective effects against chronic hepatitis B (CHB) in Japanese, Korean and other Asian populations, including Chinese and Thai individuals (Pmeta = 4.40×10−19 for rs3077 and Pmeta = 1.28×10−15 for rs9277542). These results suggest that the associations between the HLA-DP locus and the protective effects against persistent HBV infection and with clearance of HBV were replicated widely in East Asian populations; however, there are no reports of GWAS in Caucasian or African populations. Based on the GWAS in this study, there were no significant SNPs associated with HCC development. To clarify the pathogenesis of CHB and the mechanisms of HBV clearance, further studies are necessary, including functional analyses of the HLA-DP molecule

Guidelines for the management of biliary tract and ampullary carcinomas: surgical treatment

The only curative treatment in biliary tract cancer is surgical treatment. Therefore, the suitability of curative resection should be investigated in the first place. In the presence of metastasis to the liver, lung, peritoneum, or distant lymph nodes, curative resection is not suitable. No definite consensus has been reached on local extension factors and curability. Measures of hepatic functional reserve in the jaundiced liver include future liver remnant volume and the indocyanine green (ICG) clearance test. Preoperative portal vein embolization may be considered in patients in whom right hepatectomy or more, or hepatectomy with a resection rate exceeding 50%–60% is planned. Postoperative complications and surgery-related mortality may be reduced with the use of portal vein embolization. Although hepatectomy and/or pancreaticoduodenectomy are preferable for the curative resection of bile duct cancer, extrahepatic bile duct resection alone is also considered in patients for whom it is judged that curative resection would be achieved after a strict diagnosis of its local extension. Also, combined caudate lobe resection is recommended for hilar cholangiocarcinoma. Because the prognosis of patients treated with combined portal vein resection is significantly better than that of unresected patients, combined portal vein resection may be carried out. Prognostic factors after resection for bile duct cancer include positive surgical margins, especially in the ductal stump; lymph node metastasis; perineural invasion; and combined vascular resection due to portal vein and/or hepatic artery invasion. For patients with suspected gallbladder cancer, laparoscopic cholecystectomy is not recommended, and open cholecystectomy should be performed as a rule. When gallbladder cancer invading the subserosal layer or deeper has been detected after simple cholecystectomy, additional resection should be considered. Prognostic factors after resection for gallbladder cancer include the depth of mural invasion; lymph node metastasis; extramural extension, especially into the hepatoduodenal ligament; perineural invasion; and the degree of curability. Pancreaticoduodenectomy is indicated for ampullary carcinoma, and limited operation is also indicated for carcinoma in adenoma. The prognostic factors after resection for ampullary carcinoma include lymph node metastasis, pancreatic invasion, and perineural invasion

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target