Clinical Trials in Veterinary Medicine: A New Era Brings New Challenges          下载免费PDF全文

M.A. Oyama  S.S. Ellenberg  P.A. Shaw 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2017,31(4):970-978

Randomized clinical trials (RCTs) are among the most rigorous ways to determine the causal relationship between an intervention and important clinical outcome. Their use in veterinary medicine has become increasingly common, and as is often the case, with progress comes new challenges. Randomized clinical trials yield important answers, but results from these studies can be unhelpful or even misleading unless the study design and reporting are carried out with care. Herein, we offer some perspective on several emerging challenges associated with RCTs, including use of composite endpoints, the reporting of different forms of risk, analysis in the presence of missing data, and issues of reporting and safety assessment. These topics are explored in the context of previously reported veterinary internal medicine studies as well as through illustrative examples with hypothetical data sets. Moreover, many insights germane to RCTs in veterinary internal medicine can be drawn from the wealth of experience with RCTs in the human medical field. A better understanding of the issues presented here can help improve the design, interpretation, and reporting of veterinary RCTs.  相似文献   

Genetic relationships between meat quality traits and fatty acid composition in Japanese black cattle          下载免费PDF全文

Keiichi Inoue  Noriaki Shoji  Takeshi Honda  Kenji Oyama 《Animal Science Journal》2017,88(1):11-18

Genetic parameters were estimated to investigate the relationships between meat quality traits and fatty acid composition from 11 855 Japanese Black cattle. The meat quality traits included beef marbling score (BMS), beef color score, firmness of beef (FIR), texture of beef (TEX) and beef fat color score (BFS). The data on fatty acid composition included oleic acid and monounsaturated fatty acids (MUFA) contents, the ratio of MUFA to saturated fatty acids (MUS) and the ratio of elongation. The heritability estimates for meat quality traits ranged from moderate (0.30) to high (0.72). The strong genetic correlations between them were useful for simultaneous genetic improvement. In addition, high heritability estimates of fatty acid composition, ranging from 0.60 to 0.63, indicated that they could also be improved genetically. The genetic correlations of fatty acid composition with BMS, FIR and TEX were weak and negative. In contrast, positive and stronger genetic correlations were found between BFS and fatty acid composition, in particular, related to the level of unsaturation (0.77 and 0.79 for MUFA and MUS, respectively). This implies that improving the level of unsaturation makes fat darker (more yellow) and thus requires balancing with BFS.  相似文献   

More on cultivating veterinarian-scientists     

Hawkins E  Hall J  Cohn L  Buechner-Maxwell V  Oyama M  Barton MH  Olby N  Khanna C  Marks S  McFarlane D  Toll J 《Journal of the American Veterinary Medical Association》2010,237(12):1367

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Nebulin and N-WASP cooperate to cause IGF-1-induced sarcomeric actin filament formation     

Takano K  Watanabe-Takano H  Suetsugu S  Kurita S  Tsujita K  Kimura S  Karatsu T  Takenawa T  Endo T 《Science (New York, N.Y.)》2010,330(6010):1536-1540

Insulin-like growth factor 1 (IGF-1) induces skeletal muscle maturation and enlargement (hypertrophy). These responses require protein synthesis and myofibril formation (myofibrillogenesis). However, the signaling mechanisms of myofibrillogenesis remain obscure. We found that IGF-1-induced phosphatidylinositol 3-kinase-Akt signaling formed a complex of nebulin and N-WASP at the Z bands of myofibrils by interfering with glycogen synthase kinase-3β in mice. Although N-WASP is known to be an activator of the Arp2/3 complex to form branched actin filaments, the nebulin-N-WASP complex caused actin nucleation for unbranched actin filament formation from the Z bands without the Arp2/3 complex. Furthermore, N-WASP was required for IGF-1-induced muscle hypertrophy. These findings present the mechanisms of IGF-1-induced actin filament formation in myofibrillogenesis required for muscle maturation and hypertrophy and a mechanism of actin nucleation.  相似文献   

Molecular mapping of a gene conferring resistance to Aphanomyces root rot (black root) in sugar beet (<Emphasis Type="Italic">Beta vulgaris</Emphasis> L.)     

Kazunori Taguchi  Kazuyuki Okazaki  Hiroyuki Takahashi  Tomohiko Kubo  Tetsuo Mikami 《Euphytica》2010,173(3):409-418

Caused by Aphanomyces cochlioides Drechsler, Aphanomyces root rot is a serious disease of sugar beet (Beta vulgaris L.), for which sources of resistance are scarce. To identify the segregation pattern of the rare resistance trait found in Japanese sugar beet line ‘NK-310mm-O’, F₁ and BC₁F₂ seedings, drawn from a cross between ‘NK-310mm-O’ and susceptible line ‘NK-184mm-O’, were inoculated with zoospores and their survival evaluated in the greenhouse. Resistance segregation followed was that of a single dominant gene, which was designated Acr1 (Aphanomyces cochlioides resistance 1). Molecular markers tightly linked to Acr1 were identified by bulked segregant analysis of two BC₁F₂ populations. Fourteen AFLP markers linked to Acr1 were identified, the closest located within ±3.3 cM. Three F₅ lines and two BC₂F₁ lines, selected on the basis of their Acr1-AFLP markers, were tested for their resistance to Aphanomyces root rot in a highly infested field. Results indicated that Acr1 conferred significant resistance to Aphanomyces root rot at the field level. Based on its linkage with CAPS marker tk, a representative marker for chromosome III, Acr1 was located on this chromosome. The clear linkage between tk and Rhizomania resistance trait Rz1, suggests the clustering of major disease resistance genes on chromosome III.  相似文献   

Monoclonal antibodies preventing invasion of Neospora caninum tachyzoites into host cells   总被引：1，自引：0，他引：1  

Uchida Y  Ike K  Kurotaki T  Ito A  Imai S 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2004,66(11):1355-1358

Twelve monoclonal antibodies (MAbs) against Neospora caninum tachyzoites were produced to specify the antigens related to the invasion of tachyzoites into host cells. In the assay to evaluate the inhibition activity, all these MAbs prevented the cultured Vero cells from the invading by the tachyzoites. These MAbs recognized approximately a 73 kDa antigen in Western blot analysis. Immunofluorescence assay and immune electron microscopy revealed that this 73 kDa antigen is a part of the surface antigens of N. caninum tachyzoite, and that the tachyzoite antigen identified plays an important role for invasion of host cells.  相似文献   

The first record of sucking louse, Neohaematopinus callosciuri, infesting pallas squirrels in Japan     

Shinozaki Y  Yoshizawa K  Murata K  Shiibashi T  Kimura J  Maruyama S  Hayama Y  Yoshida H  Nogami S 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2004,66(3):333-335

A species of sucking louse, Neohaematopinus callosciuri, was found for the first time in Japan. The species was found on an invasive species of squirrel, Pallas squirrel, Callosciurus erythraeus, in the Kamakura district, Kanagawa Prefecture, Japan. A total of 52 lice were obtained from 22 of 104 squirrels captured. The lice were about three times more prevalent in male squirrels than in females and were detected most frequently in the winter. As N. callosciuri has never been reported on wild animals in Japan, this species probably was introduced into Japan along with their host, Pallas squirrels.  相似文献   

Measurements of plasma endothelin immunoreactivity in healthy cats and cats with cardiomyopathy     

Prosek R  Sisson DD  Oyama MA  Biondo AW  Solter PE 《Journal of veterinary internal medicine / American College of Veterinary Internal Medicine》2004,18(6):826-830

Plasma concentrations of endothelin-1 (ET-1), the most potent endogenous pressor substance discovered to date, are abnormally high in humans with congestive heart failure (CHF), and they correlate with the degree of functional impairment. We sought first to validate a human sandwich ELISA kit that targets that portion of the amino acid sequence that is identical in cats. The assay demonstrated linearity (R2 = .9968) and parallelism (P = .5339), recovery of spiked human ET-1 in cat plasma averaged 98.7%, and intraassay precision had a coefficient of variation <10%. We subsequently determined ET-1 immunoreactivity in healthy cats and in cats with myocardial disease with and without CHF, systemic thromboembolism (STE), or both. Plasma ET-1 immunoreactivity was measured in 12 healthy cats and in 28 cats with primary myocardial disease, including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), or restrictive or unclassified cardiomyopathy (RCM and UCM), respectively. Plasma ET mean (95% CI) concentrations were 0.777 (0.6536-0.924) fmol/mL in the control cats, 1.427 (0.922-2.209) fmol/mL in 12 cats with cardiomyopathy (HCM = 11, RCM/UCM = 1) but without CHF or evidence of STE, and 2.360 (1.666-3.343) fmol/mL in 16 cats with cardiomyopathy (HCM = 8, RCM/UCM = 7, DCM = 1) and CHF (n = 15) or STE (n = 4). Plasma immunoreactivity of ET-1 was significantly higher in cats with myocardial disease without CHF/STE versus normal cats (P < .05) and in cats with myocardial disease with CHF/STE versus normal cats (P < .001).  相似文献   

Carcinogenicity of biphenyl in mice by two years feeding     

Umeda Y  Aiso S  Yamazaki K  Ohnishi M  Arito H  Nagano K  Yamamoto S  Matsushima T 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2005,67(4):417-424

Carcinogenicity and chronic toxicity of biphenyl was examined in the male and female BDF1 mice fed a diet containing biphenyl at 667, 2,000 or 6,000 ppm for 2 years. There was no difference in survival rate between any biphenyl-containing diet-fed group of either sex and the respective control. Body weights of the males and females fed 6,000 ppm diet were significantly lower than the respective control. Incidences of hepatocellular carcinomas and hepatocellular adenomas in the females fed diets containing biphenyl were significantly increased in a dose-related manner, and exceeded a range of the historical control data in the Japan Bioassay Research Center. Incidences of basophilic cell foci in the liver were increased in the females fed 2,000 and 6,000 ppm diets. There was no increase in tumor or tumor-related lesion in the males fed diets containing biphenyl. Chronic toxicity of biphenyl was characterized by increased incidences of urothelial desquamation in the renal pelvis in males and females and mineralization in the inner stripe of renal outer medulla in females, as well as changes in serum levels of BUN, ALP and some electrolytes in males and females. In conclusion, the 2-year oral administration of biphenyl-containing diets induced pre-neoplastic and neoplastic lesions in the liver of females and non-neoplastic lesions in the kidney of males and females. Causative factors for the biphenyl-induced hepatocarcinogenicity were discussed in light of our published finding of peroxisome proliferation.  相似文献   

High susceptibility of Djungarian hamsters (Phodopus sungorus) to the infection with Babesia microti supported by hemodynamics     

Ike K  Komatsu T  Murakami T  Kato Y  Takahashi M  Uchida Y  Imai S 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2005,67(5):515-520

As the comparative study was carried out on the susceptibility by the pursuit of parasitemia among the Djungarian, Syrian, and Chinese hamsters as well as BALB/c mice infected with the Syrian hamster-adapted Babesia microti strain, and Djungarian hamsters showed the highest parasitemia among them. Then, the other hematological parameters were pursued in the Djungarian hamsters infected with the hamster-adapted B. microti strain. Remarkable symptoms observed were hemoglobinuria clinically, anemia hematologically, and splenomegaly macroscopically during all over the observation period for 24 weeks post infection (PI). Parasitemia began to rise at 2 weeks and peaked at 4 weeks PI. After that, parasitemia decreased gradually but was maintained with a level of about 10% on average until 24 weeks PI at the end of the experiment. A decrease in the RBC count, Hb, and PCV, and an increase in the reticulocyte and WBC counts due to the development of immature neutrophils, lymphocytes and monocytes were recognized together with a rise of parasitemia. The hamsters had macrocytic hypochromic anemia due to the increase of MCV and the decrease of MCHC in the growth phase of the parasite. It was considered that the Djungarian hamsters will be useful for the infection examination, isolation, maintenance, and passage of B. microti in laboratory.  相似文献