Cross-breed comparisons identified a critical 591-kb region for bovine carcass weight QTL (CW-2) on chromosome 6 and the Ile-442-Met substitution in NCAPG as a positional candidate

<p>Abstract</p> <p>Background</p> <p>Growth-related traits have been mapped on bovine chromosome 6 (BTA 6) in various bovine breed populations. We previously mapped a significant quantitative trait locus (QTL) for carcass and body weight (<it>CW-2</it>) between 38 and 55 cM on BTA 6 using a Japanese Black half-sib family. Additional QTL mapping studies detected four QTL for body or carcass weight that overlapped with <it>CW-2 </it>in Japanese Black and Japanese Brown half-sib families. To map the region in greater detail, we applied cross-breed comparisons of haplotypes that have been shown to be powerful in canine.</p> <p>Results</p> <p>We used 38 microsatellite markers to search for a shared <it>Q </it>(increasing carcass and/or body weight) haplotype within the 17-cM <it>CW-2 </it>region among five sires. Linkage disequilibrium mapping using maternal alleles of the offspring showed that an 815-kb shared <it>Q </it>haplotype was associated with body or carcass weight in both breeds. The addition of 43 single nucleotide polymorphism (SNP) markers narrowed the region to 591 kb containing 4 genes. The SNP changing Ile-442 to Met in <it>NCAPG </it>(chromosome condensation protein G) was significantly associated with carcass weight (<it>p </it>< 1.2 × 10^-11) in a large Japanese Black population as well as in the five families. The <it>Q </it>allele of the SNP was also associated with a larger longissimus muscle area and thinner subcutaneous fat thickness in steers of all five families, indicating that the <it>CW-2 </it>locus is pleiotropic and favorable for marker-assisted selection of beef cattle.</p> <p>Conclusion</p> <p>A 591-kb critical region for <it>CW-2 </it>was identified. The SNP changing Ile-442 to Met in <it>NCAPG </it>(chromosome condensation protein G) can be used as a positional candidate of <it>CW-2 </it>for marker-assisted selection.</p

Safety analysis of EpzicomR (lamivudine/abacavir sulfate) in post-marketing surveillance in Japan

Purpose: To obtain safety and effectiveness data on a combined anti-HIV drug, Epzicom (abacavir 600mg/lamivudine 300mg), a post-marketing surveillance on Epzicom that was required by the Japanese regulatory authority was conducted between January 2005 and December 2010. Methods: A joint survey (HIV-related drug [HRD] survey) has been conducted involving manufacturers of drugs for treatment of HIV infection in Japan. Safety and effectiveness data from total 624 cases (1107.3person-years) registered to the HRD surveys and received Epzicom were obtained. Adverse drug reactions (ADRs) were defined as adverse events (AE) of which association with Epzicom could not be \u27ruled out\u27. Results: It was found that the incidence of ADR was 32.4% (202/624 cases) on the case basis. In addition, the frequently reported ADR included hyperlipidaemia (59 cases), hypertriglyceridaemia (21 cases), blood bilirubin increased (19 cases), gamma-glutamyltransferase increase (14 cases), blood triglyceride increase (14 cases) and rash (14 cases). Serious AEs were seen in 19 patients (30 events), including one death (no evident association with Epzicom). There were four cases (0.6%) of survey-defined \u27hypersensitivity\u27, and the incidence was 0.9% (4/445) among abacavir naive patients; none of which was reported as serious. No case of myocardial infarction was reported. One pregnant case who delivered a normal baby by caesarean section was reported to have experienced aggravation of anaemia and nausea. Conclusions: The post-marketing surveillance indicated that the incidence of both ischaemic heart disease and hypersensitivity associated with Epzicom was considerably low, suggesting that this drug can be safely used in the Japanese population

Safety analysis of ZiagenR (abacavir sulfate) in postmarketing surveillance in Japan

Purpose: Abacavir is a nucleoside reverse transcriptase inhibitor indicated for human immunodeficiency virus (HIV) infection. In Japan, ZiagenR (300-mg abacavir sulfate) has been marketed since 1999. To obtain safety data on Ziagen, a mandatory postmarketing surveillance was conducted between September 1999 and September 2009. Methods: A joint survey [HIV-related Drug Surveys (HRD)] has been conducted involving manufacturers of drugs for HIV treatment in Japan. Safety data from total 643 cases (1345.7person-years) registered to the HRD surveys and received Ziagen were obtained. Adverse drug reaction (ADR) was defined as adverse event of which association with abacavir could not be "ruled out." Results: It was found that the overall frequency of ADR was 47.6% (306/643); the common ADRs were "hyperlipidemia," "nausea," "increased γ-glutamyltransferase level," "increased blood triglycerides," "abnormal hepatic function," and so on. Serious adverse events were reported in 65 subjects; however, none of the three fatal cases were clearly associated with Ziagen use. The survey-defined hypersensitivity has been infrequently reported in 15 subjects (2.3%). Although some studies had indicated of the association between abacavir and myocardial infarction, no ischemic heart diseases were reported in the present survey. Two of the three pregnant cases delivered normal neonates (one induced abortion). Conclusions: During the mandatory postmarketing survey of Ziagen, there were no cases of ischemic heart diseases, and the incidence of hypersensitivity was considerably low. These indicated that abacavir can be safely used in Japanese HIV+ population. However, the safety profile of Ziagen should be continued to be monitored through pharmacovigilance

トウキョウ イカ シカ ダイガク シガクブ シガッカ ノ リンショウ ジッシュウ シサツ ホウコク

In recent years, dental services are subdivided and complicated, moreover the social circumstances change busily. An important object of the dental education is to bring up the dentist who had rich knowledge and rich human nature adaptable to such a change. The dental students can learn knowledge and skills through lectures and phantom practices. However, it is essential to experience dental examination and treatment in the clinical field to bring up dentists such as the above dentists. In the University of Tokushima faculty of dentistry, clinical clerkship has been performed by patients' cooperation, and university students have learned a communicative competence and behavior to contact with the patients as well as the knowledge and skill of dental treatment, and improved the professional ethics. On the other hand, the patients suffering from underlying disease except dental disease such as hypertension, diabetes mellitus and heart disorder increase. When these diseases are particularly serious, scrupulous attention is necessary in the dental treatment, these patients are unsuitable for clinical clerkship if the patients are cooperative. Moreover it becomes difficult to get the patients' cooperation for clinical clerkship year by year. The improvement of dental clinical education is a matter of great urgency corresponding to such situation. Therefore we inspected a clinical clerkship in faculty of dentistry, Tokyo Medical and Dental University and collected information for improvement of clinical clerkship of the University of Tokushima, faculty of dentistry

Clinical Efficacy and Safety of Sitafloxacin 200 mg Once Daily for Refractory Genitourinary Tract Infections

The aim of this ongoing trial is to evaluate the clinical efficacy and safety of sitafloxacin (STFX) 200 mg once daily (QD) for 7 days in patients with refractory genitourinary tract infections, which include recurrent or complicated cystitis, complicated pyelonephritis, bacterial prostatitis, and epididymitis. The primary endpoint is the microbiological efficacy at 5-9 days after the last administration of STFX. Recruitment began in February 2021, and the target total sample size is 92 participants

Dietary fiber intake and risk of incident disabling dementia: the Circulatory Risk in Communities Study

OBJECTIVES: It has been hypothesized that dietary fiber intake has a beneficial impact on prevention of dementia, but the epidemiological evidence is scant. We sought to examine whether dietary fiber intake is inversely associated with risk of dementia requiring care under the national insurance (disabling dementia). METHODS: The study setting was the Circulatory Risk in Communities Study, involving 3739 Japanese individuals aged 40-64 years at the dietary surveys (1985-99). Dietary fiber intake was estimated using the 24-hour dietary recall method. Incident disabling dementia was followed up from 1999 through 2020. Disabling dementia was further classified into that with or without a history of stroke. Hazard ratios of disabling dementia according to quartiles of total, soluble, and insoluble fiber intake were calculated using the Cox proportional hazards model. RESULTS: During a median 19.7-year follow-up, a total of 670 cases of disabling dementia developed. Dietary fiber intake was inversely associated with risk of dementia: the multivariate hazards ratios (95% confidence intervals) were 0.83 (0.67-1.04), 0.81 (0.65-1.02), and 0.74 (0.57-0.96) for individuals with the second, third, and highest quartiles of dietary fiber intake, respectively, as compared with the lowest quartile (P for trend = 0.03). The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke. As for fiber-containing foods, potatoes, but not vegetables or fruits, showed a similar association. CONCLUSIONS: Dietary fiber intake, especially soluble fiber, was inversely associated with risk of disabling dementia in a general Japanese population

Pancreatic RECK inactivation promotes cancer formation, epithelial-mesenchymal transition, and metastasis

膵癌悪性化の分子機構解明 --RECK発現の低下が膵癌の浸潤・転移を引き起こす--. 京都大学プレスリリース. 2023-09-19.RECK is downregulated in various human cancers; however, how RECK inactivation affects carcinogenesis remains unclear. We addressed this issue in a pancreatic ductal adenocarcinoma (PDAC) mouse model and found that pancreatic Reck deletion dramatically augmented the spontaneous development of PDAC with a mesenchymal phenotype, which was accompanied by increased liver metastases and decreased survival. Lineage tracing revealed that pancreatic Reck deletion induced epithelial-mesenchymal transition (EMT) in PDAC cells, giving rise to inflammatory cancer-associated fibroblast–like cells in mice. Splenic transplantation of Reck-null PDAC cells resulted in numerous liver metastases with a mesenchymal phenotype, whereas reexpression of RECK markedly reduced metastases and changed the PDAC tumor phenotype into an epithelial one. Consistently, low RECK expression correlated with low E-cadherin expression, poor differentiation, metastasis, and poor prognosis in human PDAC. RECK reexpression in the PDAC cells was found to downregulate MMP2 and MMP3, with a concomitant increase in E-cadherin and decrease in EMT-promoting transcription factors. An MMP inhibitor recapitulated the effects of RECK on the expression of E-cadherin and EMT-promoting transcription factors and invasive activity. These results establish the authenticity of RECK as a pancreatic tumor suppressor, provide insights into its underlying mechanisms, and support the idea that RECK could be an important therapeutic effector against human PDAC

マウスリンパ組織におけるレプチンレセプターの発現

The mammalian thymus involutes with age. Both the decrease of lymphocyte-accumulated region and the replacement by fat tissue begin at puberty and continue throughout life. In the mouse thymus, though no typical fat cells are found at birth, fat cells appeared at the latest 3 weeks old preceding to the atrophy of cortical and medullary regions. Physiological functions of fat cells proliferated and differentiated in the thymus after birth are unknown. As fat cells appeared in the 3-week-old mouse thymus have shown to express leptin mRNA, we examined whether leptin receptor type b (OBRL) is expressed or not in the thymus and, in comparison, in the secondary lymphoid tissues, spleen, mesenteric lymph node and Peyer' s patch. OBRL mRNA was detected in both thymus and all secondary lymphoid tissues examined by RTPCR method. Furthermore, OBRL mRNA was also detected in the isolated cells with mouse-lymphocyte separation medium from both thymus and spleen free cells washed out in saline from dissected tissues. It is suggested that fat cells differenciated as early as 3 weeks old in the thymus produce leptin and affect other thymus cells, lymphocytes probably, through OBRL. It remains to be clarified whether the leptin-OBRL interaction influences age involution in the thymus

Drug efficacy against aortic dissection

Objective: Aortic dissection is a life-threatening disease. At present, the only therapeutic strategies available are surgery and antihypertensive drugs. Moreover, the molecular mechanisms underlying the onset of aortic dissection are still unclear. We established a novel aortic dissection model in mice using pharmacologically induced endothelial dysfunction. We then used the Japanese Adverse Drug Event Report database to investigate the role of pitavastatin in preventing the onset of aortic dissection. Methods and results: To induce endothelial dysfunction, Nω-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, was administered to C57BL/6 mice. Three weeks later, angiotensin II (Ang II) and β-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, were administered with osmotic mini-pumps. False lumen formation was used as the pathological determinant of aortic dissection. The incidences of aortic dissection and death from aneurysmal rupture were significantly higher in the Nω-nitro-L-arginine methyl ester, Ang II, and BAPN (LAB) group than they were in the Ang II and BAPN (AB) group. Pitavastatin was administered orally to LAB mice. It significantly lowered the incidences of dissection and rupture. It also decreased inflammation and medial degradation, both of which were exacerbated in the LAB group. The Japanese Adverse Drug Event Report database analysis indicated that there were 113 cases of aortic dissection out of 95 090 patients (0.12%) not receiving statins but only six cases out of 16 668 patients receiving statins (0.04%) (odds ratio: 0.30; P=0.0043). Conclusion: Our results suggest that endothelial dysfunction is associated with the onset of aortic dissection and pitavastatin can help prevent this condition