BACKGROUND & AIMS: The hazards of using optic nerve (as opposed to optic tract and more distal components of the optic system) to study axonal transport were highlighted by observing the fate of [14C]serine and [3H]glycerol injected into the rabbit eye. Despite prior blockage of axonal transport with colchicine, appreciable radioactivity rapidly appeared in the optic nerve adjacent to the injected eye. Radioactivity decreased exponentially along the entire optic chiasm. Counts were distributed among the lipid, protein, and acid-soluble fractions. Separation of optic nerve lipids revealed appreciable labeling of most lipid classes including those characteristic of myelin; a markedly different labeling pattern was observed for axonally transported lipids. The data are consistent with a mechanism involving extra-axonal diffusion of precursor into the surrounding glia followed by incorporation into lipids and proteins of those cells and ultimately myelin. The phenomenon is discussed in relation to possible errors that were made in interpreting earlier experiments.

背景与目标： 通过观察注射到兔眼中的 [14C] 丝氨酸和 [3H] 甘油的命运，突出了使用视神经 (相对于视神经系统和更多视神经系统的远端成分) 来研究轴突运输的危害。尽管先前用秋水仙碱阻断了轴突运输，明显的放射性迅速出现在与注射的眼睛相邻的视神经中。放射性沿整个视交叉呈指数下降。计数分布在脂质、蛋白质和酸溶性部分中。视神经脂质的分离揭示了大多数脂质类别的明显标记，包括髓磷脂的特征; 对于轴突运输的脂质观察到明显不同的标记模式。数据与涉及前体轴突外扩散到周围神经胶质的机制一致，然后掺入到这些细胞的脂质和蛋白质以及最终髓磷脂中。讨论了与解释早期实验中可能出现的错误有关的现象。

BACKGROUND & AIMS: :End-expiratory occlusion test (EEOT) has been proposed as a preload responsiveness test that overcomes several limitations of pulse pressure (PPV) and stroke volume (SVV) variations. We compared the ability of EEOT versus SVV and PPV to predict fluid responsiveness during the increase of the vasomotor tone in a rabbit model of hemorrhage. Ten rabbits were anesthetized, paralyzed, and mechanically ventilated during basal load (BL), after progressive blood withdrawal (BW), and after volume replacement. Other two sets of data were obtained during vasomotor increase by phenylephrine (PHE) infusion in BL and BW. We estimated the change of stroke volume (∆SVEEOT) and aortic flow (∆AoFEEOT) during the EEOT. PPV and SVV were obtained by the variation of beat-to-beat PP and SV, respectively. Baseline PPV, SVV, ∆SVEEOT, and ∆AoFEEOT increased significantly after BW, with a decrease of aortic flow (P < 0.05). PHE induced a significant decrease of PPV and SVV, but without affecting ∆SVEEOT, and ∆AoFEEOT. We conclude that ∆SV and ∆AoF during EEOT kept the ability to predict fluid responsiveness during PHE infusion in a rabbit hemorrhage model. This result may suggest the advantage of EEOT with respect to SVV and PPV in predicting fluid responsiveness during vasomotor tone increase.

背景与目标： : 呼气末阻塞测试 (EEOT) 已被提议作为一种预载响应性测试，克服了脉压 (PPV) 和中风量 (SVV) 变化的几个限制。我们比较了EEOT与SVV和PPV在兔出血模型中血管舒缩张力增加期间预测液体反应性的能力。在基础负荷 (BL)，进行性抽血 (BW) 和容量置换后，将十只兔子麻醉，瘫痪和机械通气。在BL和BW中输注去氧肾上腺素 (PHE) 增加血管舒缩期间获得了其他两组数据。我们估计了EEOT期间中风量 (∆ sveeot) 和主动脉血流 (∆ aofeeot) 的变化。PPV和SVV分别通过节拍PP和SV的变化获得。基线PPV、SVV、 ∆ sveeot和 ∆ aofeeot在BW后显著增加，主动脉血流减少 (p  <  0.05)。PHE引起PPV和SVV的显着降低，但不影响 ∆ sveeot和 ∆ aofeeot。我们得出的结论是，EEOT期间的 ∆ sv和 ∆ aof在兔出血模型中保持了预测PHE输注期间液体反应性的能力。该结果可能表明EEOT相对于SVV和PPV在预测血管舒缩张力增加期间的液体反应性方面具有优势。

BACKGROUND & AIMS: :Anandamide (AEA) presents the four double bonds in the cis configuration, deriving from the arachidonic acid moiety. In the context of an antisense strategy based on the double bond configuration, all-trans AEA (t-AEA) was synthesized in high yield starting from all-trans methyl arachidonate and ethanolamine in the presence of KCN. t-AEA was assayed on rabbit platelet aggregation, obtaining effect only at high concentrations (>10(-4) M) after an also concentration-dependent lag phase. At lower concentrations it inhibited PAF-induced rabbit platelet aggregation with an IC(50)=4.6 x 10(-6) M. In contrast to anandamide, the activation of platelets was not due to the conversion of t-AEA to trans arachidonic acid, as ascertained by negative results with FAAH inhibitors. However, t-AEA was found to be a substrate for fatty acid amide hydrolase (FAAH), the enzyme that cleaves anandamide and regulates in vivo the magnitude and duration of the signaling induced by this lipid messenger.

背景与目标： : Anandamide (AEA) 在顺式构型中呈现四个双键，源自花生四烯酸部分。在基于双键构型的反义策略的背景下，在KCN存在下，从全反式甲基花生四烯酸和乙醇胺开始，高产率合成了全反式AEA (t-aea)。t-AEA对兔血小板聚集进行了测定，仅在浓度依赖性滞后阶段后才在高浓度 (>10(-4) M) 下获得效果。在较低的浓度下，它以IC(50)= 4.6 × 10(-6) M抑制PAF诱导的兔血小板聚集。与anandamide相反，血小板的活化不是由于t-AEA转化为反式花生四烯酸，这是由FAAH抑制剂的阴性结果确定的。然而，发现t-AEA是脂肪酸酰胺水解酶 (FAAH) 的底物，该酶可裂解anandamide并在体内调节由该脂质信使诱导的信号传导的幅度和持续时间。

BACKGROUND & AIMS: UNLABELLED:Several lines of evidence have demonstrated that C-reactive protein (CRP) is associated with oxidative stress; however, the precise co-localization between CRP and oxidative stress markers in atherosclerotic lesions is not fully established. In this study, we focused on two oxidative stress markers, dityrosine (DY) and N(epsilon)-(hexanoyl)lysine (HEL), which had not previously been investigated in relation to CRP in atherosclerotic lesions. AIM:We investigated the production and localization of DY, HEL, and CRP in early-stage and moderately progressed fatty lesions of cholesterol-fed rabbits by immunohistochemistry using specific monoclonal antibodies to examine the co-localization between CRP and oxidative stress in atherosclerotic lesions. METHODS:Rabbit atherosclerotic specimens were obtained from New Zealand White rabbits fed a diet containing 1.0% cholesterol for 12 weeks. All specimens were fixed in formalin for histological examinations. RESULTS:CRP-positive cells in rabbit early-stage and moderately progressed fatty lesions were detected mostly in the macrophage-derived foam cell-rich areas. Both DY and HEL were also detected in foam cell-rich areas in both lesions, where they were primarily co-localized with CRP-positive cells. CONCLUSION:Our results suggest that the generation of oxidative stress markers, DY and HEL, may be mediated by CRP in atherosclerotic lesions, and that CRP may be associated with oxidative stress in rabbit atherosclerotic lesions.

背景与目标：

BACKGROUND & AIMS: :Cell-based tendon therapies with tenocytes as a cell source need effective tenocyte in vitro expansion before application for tendinopathies and tendon injuries. Supplementation of tenocyte culture with biomolecules that can boost proliferation and matrix synthesis is one viable option for supporting cell expansion. In this in vitro study, the impacts of ascorbic acid or PDGF-BB supplementation on rabbit Achilles tenocyte culture were studied. Namely, cell proliferation, changes in gene expression of several ECM and tendon markers (collagen I, collagen III, fibronectin, aggrecan, biglycan, decorin, ki67, tenascin-C, tenomodulin, Mohawk, α-SMA, MMP-2, MMP-9, TIMP1, and TIMP2) and ECM deposition (collagen I and fibronectin) were assessed. Ascorbic acid and PDGF-BB enhanced tenocyte proliferation, while ascorbic acid significantly accelerated the deposition of collagen I. Both biomolecules led to different changes in the gene expression profile of the cultured tenocytes, where upregulation of collagen I, Mohawk, decorin, MMP-2, and TIMP-2 was observed with ascorbic acid, while these markers were downregulated by PDGF-BB supplementation. Vice versa, there was an upregulation of fibronectin, biglycan and tenascin-C by PDGF-BB supplementation, while ascorbic acid led to a downregulation of these markers. However, both biomolecules are promising candidates for improving and accelerating the in vitro expansion of tenocytes, which is vital for various tendon tissue engineering approaches or cell-based tendon therapy.

背景与目标： : 以肌腱细胞为细胞来源的基于细胞的肌腱疗法在用于肌腱病和肌腱损伤之前需要有效的肌腱细胞体外扩增。用可以促进增殖和基质合成的生物分子补充tenocyte培养物是支持细胞扩增的一种可行选择。在这项体外研究中，研究了抗坏血酸或pdgf-bb补充剂对兔跟腱细胞培养的影响。即细胞增殖，几种ECM和肌腱标记物 (胶原蛋白I，胶原蛋白III，纤连蛋白，聚集蛋白聚糖，双聚糖，decorin，ki67，tenascin-C，tenomodulin，Mohawk，α-SMA，MMP-2，MMP-9，TIMP1，和TIMP2) 和ECM沉积 (胶原蛋白I和纤连蛋白) 进行了评估。抗坏血酸和pdgf-bb增强了腱细胞的增殖，而抗坏血酸则显着加速了胶原蛋白I的沉积。两种生物分子导致培养的肌腱细胞的基因表达谱的不同变化，其中抗坏血酸观察到胶原蛋白I，莫霍克，decorin，MMP-2和TIMP-2的上调，而这些标记物通过补充pdgf-bb下调。反之亦然，通过补充pdgf-bb，纤连蛋白，双聚糖和腱生蛋白C上调，而抗坏血酸导致这些标记物下调。然而，这两种生物分子都是改善和加速肌腱细胞体外扩增的有希望的候选者，这对于各种肌腱组织工程方法或基于细胞的肌腱治疗至关重要。

BACKGROUND & AIMS: :cDNAs for hyaluronic acid synthases (HAS2 and HAS3) were cloned from a cDNA library of cultured rabbit synovial membrane cells. The cDNA encoding the open reading frame of rabbit HAS2 and HAS3 was 1659 nucleotides in length with a predicted molecular mass of about 63 kDa. The amino acid sequence showed that the rabbit HAS2 was 98.7 and 98.4%, and HAS3 was 98.2 and 97.5% identical with human and mouse forms of the proteins, respectively. The predicted sequences for hyaluronic acid (HA) binding motifs and the catalytic domains related to beta 1-4 and beta 1-3 linkages, essential for HA synthesis, were almost conserved in both rabbit HAS2 and HAS3, similarly to human and mouse HASs. RT-PCR analysis and in situ hybridization revealed that the mRNA of HAS2 was highly expressed in the synovial membrane and articular cartilage, whereas the expression of HAS3 mRNA was slightest in these tissues. Thus, it is demonstrated that rabbit HASs are highly conserved in sequence content as compared to the human and mouse homologues described previously, and that HAS2 is predominantly expressed in the synovial membrane and articular cartilage, but HAS3 is not.

背景与目标： : 从培养的兔滑膜细胞的cDNA文库中克隆了透明质酸合酶 (HAS2和HAS3) 的cDNA。编码兔HAS2和HAS3的开放阅读框的cDNA长度为1659个核苷酸，预测分子量约为63 kDa。氨基酸序列显示兔HAS2为98.7和98.4%，HAS3分别与人和小鼠形式的蛋白质98.2和97.5% 相同。透明质酸 (HA) 结合基序的预测序列以及与HA合成必不可少的 β1-4和 β1-3键相关的催化结构域，在兔HAS2和HAS3中几乎都是保守的，类似于人和小鼠HASs。Rt-pcr分析和原位杂交显示，HAS2的mRNA在滑膜和关节软骨中高表达，而HAS3 mRNA在这些组织中的表达最小。因此，已证明与先前描述的人和小鼠同源物相比，兔HASs的序列含量高度保守，并且HAS2主要在滑膜和关节软骨中表达，而HAS3则不表达。

BACKGROUND & AIMS: :Separation of fractions enriched in hypertrophic cells and proliferative cells has been achieved by density gradient centrifugation of cells from collagenase digests of rabbit epiphyseal cartilage. Concentrated suspensions of cells are centrifuged on a continuous Percoll density gradient. Hypertrophic cells remain in the upper part of the gradient and proliferative zone cells move to the lower regions. The resultant fractions show differences in mean cell diameter, alkaline phosphatase activity, morphology and synthetic activity in culture. Fractions rich in hypertrophic cells contain larger cells and more alkaline phosphatase activity than those enriched in proliferative cells. In culture the hypertrophic cells flatten as large irregular polygonal cells, whereas proliferative fractions form smaller spindle-shaped cells. In micromass culture hypertrophic fractions incorporate less 35S-sulphate and 14C-proline, and less tritiated thymidine than do proliferative fractions. These results suggest a general reduction in matrix and DNA synthesis with the attainment of the fully differentiated hypertrophic state, coincident with the expression of alkaline phosphatase activity and mineralisation of the cartilage matrix.

背景与目标： : 通过从兔epi骨软骨的胶原酶消化物中分离细胞的密度梯度离心，可以分离富含肥厚细胞和增殖细胞的级分。在连续的Percoll密度梯度上离心细胞的浓缩悬浮液。肥厚细胞保留在梯度的上部，增殖区细胞移动到下部区域。所得组分在培养物中显示出平均细胞直径，碱性磷酸酶活性，形态和合成活性的差异。富含肥厚细胞的组分比富含增殖细胞的组分含有更大的细胞和更多的碱性磷酸酶活性。在培养物中，肥厚细胞变平为大型不规则多边形细胞，而增殖部分形成较小的纺锤形细胞。在微质量培养中，肥厚级分与增殖级分相比，含有更少的35s硫酸盐和14c-脯氨酸，以及更少的tristiate胸苷。这些结果表明，随着完全分化的肥厚状态的实现，基质和DNA合成普遍减少，与碱性磷酸酶活性的表达和软骨基质的矿化相吻合。

BACKGROUND & AIMS: :The migration and spreading of the corneal epithelial cells adjacent to a wound is the first step in successful epithelial resurfacing. To understand the role of actin filaments and microtubules of the cytoskeletal system in the spreading of corneal epithelial cells, we plated rabbit corneal epithelial cells on a fibronectin matrix and studied the effects of cytochalasin B, which inhibits actin filaments assembly, and colchicine, which inhibits microtubules assembly, on the ability of individual cells to spread. Changes in the morphology of actin filaments and microtubules were also studied using immunofluorescent microscopy. The area of spread epithelial cells depended on the concentration of fibronectin used to coat the surface. In spread cells, stress fibers of actin filaments were evenly distributed throughout the cytoplasm, whereas microtubules were observed only at the perinuclear region. The presence of cytochalasin B during the cell attachment and spreading decreased the area of the spread cells more than did colchicine. However, once the epithelial cells were spread on a fibronectin matrix, cytochalasin B and colchicine each decreased the cell area only slightly, and to the same extent. These results indicate that formation of actin filaments is more important than formation of microtubules to the spreading of corneal epithelial cells.

背景与目标： : 与伤口相邻的角膜上皮细胞的迁移和扩散是成功进行上皮表面置换的第一步。为了了解肌动蛋白丝和细胞骨架系统微管在角膜上皮细胞扩散中的作用，我们将兔角膜上皮细胞铺在纤连蛋白基质上，研究了抑制肌动蛋白丝组装的细胞松弛素B和抑制微管组装的秋水仙碱的作用，单个细胞扩散的能力。还使用免疫荧光显微镜研究了肌动蛋白丝和微管形态的变化。扩散的上皮细胞的面积取决于用于覆盖表面的纤连蛋白的浓度。在扩散细胞中，肌动蛋白丝的应力纤维均匀分布在整个细胞质中，而微管仅在核周区域观察到。细胞附着和扩散过程中细胞松弛素B的存在比秋水仙碱减少了扩散细胞的面积。然而，一旦上皮细胞散布在纤连蛋白基质上，细胞松弛素B和秋水仙碱分别仅略微降低细胞面积，并达到相同程度。这些结果表明，肌动蛋白丝的形成比微管的形成对角膜上皮细胞的扩散更为重要。

BACKGROUND & AIMS: :To define the mechanism of regulation of the protein kinase that is activated in heme deficiency and that inhibits initiation of protein synthesis, we have isolated and purified the heme-reversible form of the protein kinase from rabbit reticulocytes. The inhibitory activity is found in a single band after polyacrylamide gel electrophoresis under nondenaturing conditions. It migrates as a 95,000-dalton polypeptide in 15% sodium dodecyl sulfate/polyacrylamide gels. This purified inhibitor becomes self-phosphorylated in the presence of ATP; the phosphorylated protein and the inhibitory activity copurify. The inhibitor produces characteristic biphasic kinetics of inhibition in reticulocyte lysates and phosphorylates the 38,000-dalton subunit of eukaryotic initiation factor 2 (eIF-2); the inhibition is reversed by added eIF-2. In contrast to the heme-irreversible inhibitor, this heme-reversible inhibitor is no longer inhibitory after incubation with 20 micron hemin. Incubation with hemin also inhibits self-phosphorylation. Preincubation of the heme-reversible inhibitor in the presence of ATP potentiates the inhibition of protein synthesis in the subsequent incubation, as does treatment with N-ethylmaleimide. Phosphorylation of the heme-reversible inhibitor and inhibition of protein synthesis in the lysate due to phosphorylation of eIF-2 appear to be related. These findings suggest that hemin acts directly on the heme-reversible inhibitor.

背景与目标： : 为了确定在血红素缺乏中被激活并抑制蛋白质合成起始的蛋白激酶的调节机制，我们从兔网织红细胞中分离并纯化了血红素可逆形式的蛋白激酶。在非变性条件下，聚丙烯酰胺凝胶电泳后，在单个条带中发现了抑制活性。它作为95,000-道尔顿多肽在15% 十二烷基硫酸钠/聚丙烯酰胺凝胶中迁移。在存在ATP的情况下，这种纯化的抑制剂会自我磷酸化; 磷酸化的蛋白质和抑制活性共聚。抑制剂在网织红细胞裂解物中产生抑制的特征性双相动力学，并使真核起始因子2 (eIF-2) 的38,000-道尔顿亚基磷酸化; 通过添加的eIF-2来逆转抑制。与血红素不可逆抑制剂相反，该血红素可逆抑制剂与20微米血红素孵育后不再具有抑制作用。与血红素一起孵育也抑制自磷酸化。与N-乙基马来酰亚胺处理一样，在ATP存在下对血红素可逆抑制剂的预孵育可增强随后孵育中蛋白质合成的抑制作用。血红素可逆抑制剂的磷酸化和由于eIF-2的磷酸化引起的裂解物中蛋白质合成的抑制似乎是相关的。这些发现表明，血红素直接作用于血红素可逆抑制剂。

BACKGROUND & AIMS: :In cumulative dose-response studies, strips from bladder neck of rabbit were significantly more sensitive to stimulation with noradrenaline, phenylephrine, and methoxamine than were strips from detrusor. There was no difference between the two regions in sensitivity to isoprenaline or carbachol. From the known characteristics of these agents, it seemed unlikely that metabolic destruction or uptake could account for the different sensitivities seen. Also, neither normetanephrine nor desmethylimipramine could alter significantly the potency of noradrenaline in either area of the bladder. It seems likely that the difference in sensitivity to alpha-adrenoceptor stimulation in the bladder neck and detrusor is due to factors at the receptor level.

背景与目标： : 在累积剂量反应研究中，兔膀胱颈条对去甲肾上腺素，去氧肾上腺素和甲氧明的刺激比逼尿肌条的刺激要敏感得多。两个区域对异丙肾上腺素或卡巴胆碱的敏感性没有差异。从这些药物的已知特征来看，代谢破坏或摄取似乎不太可能解释所看到的不同敏感性。而且，去甲肾上腺素和去甲基丙咪嗪都不能显着改变膀胱任一区域中去甲肾上腺素的效力。膀胱颈和逼尿肌对 α-肾上腺素受体刺激的敏感性差异似乎是由于受体水平的因素所致。

BACKGROUND & AIMS: PURPOSE:Partial bladder outlet obstruction (PBOO) results in marked biochemical alterations in the bladder. In this study, we focused on comparison of thapsigargin sensitive sarco/endoplasmic reticulum Ca(2+) ATPase activity (SERCA) and Citrate Synthase after short term PBOO in young versus old rabbits. MATERIALS AND METHODS:A total of 20 young and 20 mature male rabbits were divided into 4 sub-groups of 5 rabbits each (4 obstructed and 1 sham-control rabbit). The rabbits in the groups were evaluated after 1, 3, 7, and 14 days of obstruction, respectively. The activities of SERCA and citrate synthase were examined as markers for sarcoplasmic reticular calcium storage and release and mitochondrial function, respectively. RESULTS:The SERCA activity of bladder body smooth muscle in the young animals increased at 7 and 14 days. For the old rabbits, the SERCA activity decreased significantly by 1 day and remained this level throughout the course of obstruction, and was significantly lower than young at all time periods. The citrate synthase activity in the young animals decreased over the 1-7 days, and then returned toward control level by 14 days following obstruction. In the old animals, citrate synthase activity of bladder body smooth muscle progressively decreased over the course of the study, and was significantly lower in the old than the young animals after 14 days obstructed. CONCLUSION:The urinary bladders of the young rabbits have a considerable greater ability to adapt to PBOO than do those of the old rabbits. The deterioration of mitochondrial and SR function may be important mechanisms underlying geriatric voiding dysfunction.

背景与目标：

BACKGROUND & AIMS: :Hereditary tyrosinemia type 1 (HT1) is a severe human autosomal recessive disorder caused by the deficiency of fumarylacetoacetate hydroxylase (FAH), an enzyme catalyzing the last step in the tyrosine degradation pathway. Lack of FAH causes accumulation of toxic metabolites (fumarylacetoacetate and succinylacetone) in blood and tissues, ultimately resulting in severe liver and kidney damage with onset that ranges from infancy to adolescence. This tissue damage is lethal but can be controlled by administration of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), which inhibits tyrosine catabolism upstream of the generation of fumarylacetoacetate and succinylacetone. Notably, in animals lacking FAH, transient withdrawal of NTBC can be used to induce liver damage and a concomitant regenerative response that stimulates the growth of healthy hepatocytes. Among other things, this model has raised tremendous interest for the in vivo expansion of human primary hepatocytes inside these animals and for exploring experimental gene therapy and cell-based therapies. Here, we report the generation of FAH knock-out rabbits via pronuclear stage embryo microinjection of transcription activator-like effector nucleases. FAH-/- rabbits exhibit phenotypic features of HT1 including liver and kidney abnormalities but additionally develop frequent ocular manifestations likely caused by local accumulation of tyrosine upon NTBC administration. We also show that allogeneic transplantation of wild-type rabbit primary hepatocytes into FAH-/- rabbits enables highly efficient liver repopulation and prevents liver insufficiency and death. Because of significant advantages over rodents and their ease of breeding, maintenance, and manipulation compared with larger animals including pigs, FAH-/- rabbits are an attractive alternative for modeling the consequences of HT1.

背景与目标： : 遗传性酪氨酸血症1型 (HT1) 是一种严重的人类常染色体隐性遗传疾病，由延胡索乙酰乙酸羟化酶 (FAH) 缺乏引起，该酶催化酪氨酸降解途径的最后一步。缺乏FAH会导致血液和组织中有毒代谢产物 (富马酰乙酰乙酸酯和琥珀酰丙酮) 的积累，最终导致严重的肝脏和肾脏损害，发病范围从婴儿期到青春期。这种组织损伤是致命的，但可以通过施用2-(2-硝基-4-三氟甲基苯甲酰基)-1,3-环己二酮 (NTBC) 来控制，后者抑制了富马基乙酰乙酸酯和琥珀酰丙酮产生的酪氨酸分解代谢。值得注意的是，在缺乏FAH的动物中，NTBC的短暂戒断可用于诱导肝损伤和伴随的再生反应，从而刺激健康肝细胞的生长。除其他外，该模型对这些动物体内人类原代肝细胞的体内扩增以及探索实验性基因疗法和基于细胞的疗法引起了极大的兴趣。在这里，我们报告了通过原核阶段胚胎显微注射转录激活因子样效应核酸酶产生的FAH敲除兔。FAH-/-兔子表现出HT1的表型特征，包括肝脏和肾脏异常，但另外还出现了频繁的眼部表现，可能是由于NTBC给药后酪氨酸的局部积累所致。我们还显示，将野生型兔原代肝细胞同种异体移植到FAH-/-兔中，可实现高效的肝脏再增殖，并防止肝功能不全和死亡。由于与啮齿动物相比具有显着优势，并且与包括猪在内的大型动物相比，它们易于繁殖，维护和操纵，因此FAH-/-兔子是模拟ht1后果的有吸引力的替代方法。

BACKGROUND & AIMS: :To induce a rabbit model of atherosclerosis at carotid artery, to visualize the lesion evolution with magnetic resonance imaging (MRI), and to characterize the lesion types by histopathology. Atherosclerosis at the right common carotid artery (RCCA) was induced in 23 rabbits by high-lipid diet following balloon catheter injury to the endothelium. The rabbits were examined in vivo with a 1.5-T MRI and randomly divided into three groups of 6 weeks (n=6), 12 weeks (n=8) and 15 weeks (n=9) for postmortem histopathology. The lesions on both MRI and histology were categorized according to the American Heart Association (AHA) classifications of atherosclerosis. Type I and type II of atherosclerotic changes were detected at week 6, i.e., nearly normal signal intensity (SI) of the injured RCCA wall without stenosis on MRI, but with subendothelial inflammatory infiltration and proliferation of smooth muscle cells on histopathology. At week 12, 75.0% and 62.5% of type III changes were encountered on MRI and histopathology respectively with thicker injured RCCA wall of increased SI on T(1)-weighted and proton density (PD)-weighted MRI and microscopically a higher degree of plaque formation. At week 15, carotid atherosclerosis became more advanced, i.e., type IV and type V in 55.6% and 22.2% of the lesions with MRI and 55.6% and 33.3% of the lesions with histopathology, respectively. Statistical analysis revealed a significant agreement (p<0.05) between the MRI and histological findings for lesion classification (r=0.96). A rabbit model of carotid artery atherosclerosis has been successfully induced and noninvasively visualized. The atherosclerotic plaque formation evolved from type I to type V with time, which could be monitored with 1.5-T MRI and confirmed with histomorphology. This experimental setting can be applied in preclinical research on atherosclerosis.

背景与目标： : 在颈动脉处诱导兔动脉粥样硬化模型，通过磁共振成像 (MRI) 可视化病变的演变，并通过组织病理学表征病变类型。在球囊导管损伤内皮后，高脂饮食在23只兔子中诱发了右颈总动脉 (RCCA) 的动脉粥样硬化。用1.5-T MRI在体内检查兔子，并随机分为三组，分别为6周 (n = 6)，12周 (n = 8) 和15周 (n = 9) 进行死后组织病理学检查。MRI和组织学上的病变均根据美国心脏协会 (AHA) 的动脉粥样硬化分类进行分类。第6周检测到I型和II型动脉粥样硬化改变，即损伤RCCA壁的信号强度 (SI) 接近正常，MRI上无狭窄，但组织病理学上有内皮下炎症浸润和平滑肌细胞增殖。在第12周，在MRI和组织病理学上分别遇到III型变化的75.0% 和62.5%，在T(1) 加权和质子密度 (PD) 加权MRI上SI增加的损伤RCCA壁较厚，并且在显微镜下斑块形成程度较高。在第15周时，颈动脉粥样硬化变得更加先进，即分别在MRI和55.6% 的病变55.6% 和22.2% 中的IV型和V型和组织病理学的病变33.3%。统计分析显示，MRI和组织学检查结果对于病变分类有显著的一致性 (p<0.05) (r = 0.96)。已成功诱导并无创可视化了兔颈动脉粥样硬化模型。动脉粥样硬化斑块形成随时间从I型演变为V型，可通过1.5-T MRI监测并通过组织形态学证实。此实验设置可用于动脉粥样硬化的临床前研究。

BACKGROUND & AIMS: :Activated H-ras genes are present in a number of skin tumors induced in animals by carcinogen treatment. The involvement of the ras oncogenes in tumorigenesis was investigated in keratoacanthomas, benign and self-regressing tumors, as well as malignant squamous cell carcinomas. Both tumors were induced in rabbit ears by repeated applications of 7,12 dimethylbenz(a)anthracene (DMBA). The rabbit H-ras gene was cloned and sequenced. PCR analysis revealed that approximately 82% of the keratoacanthoma DNAs contained an A:T to T:A transversion in codon 61. The relative levels of H-ras transcript were increased in keratoacanthomas compared to normal skin and the activated allele was expressed in tumors, even during the regressing phase. Although a G:C to A:T mutation in codon 12 of the H-ras and an activated N-ras gene were found in two squamous cell carcinomas, the frequency of H-ras activation in codon 61 was much lower (40%) in the malignant tumours induced by the same carcinogen treatment. Therefore, DMBA induced at least two types of genetic lesions in this system: H-ras activation, present in most regressing keratoacanthomas, and activation of other unidentified oncogenes which may result in the development of malignant tumors. Our observations indicate that expression of an activated H-ras gene, in this system, is neither sufficient to induce a malignant phenotype nor even capable of maintaining the growth of a benign tumor and suggest that it could be involved in tumor regression.

背景与目标： : 活化的H-ras基因存在于通过致癌物治疗在动物中诱导的许多皮肤肿瘤中。在角膜瘤，良性和自我消退的肿瘤以及恶性鳞状细胞癌中研究了ras癌基因在肿瘤发生中的作用。通过重复施用7,12二甲基苯并 (a) 蒽 (DMBA) 在兔耳中诱导了这两种肿瘤。克隆并测序了兔H-ras基因。PCR分析显示大约82% 的角化棘皮瘤dna在密码子61中含有A:T至T:A转换。与正常皮肤相比，角膜acanthomas中H-ras转录本的相对水平增加，并且即使在消退阶段，激活的等位基因也在肿瘤中表达。尽管在两个鳞状细胞癌中发现了H-ras 12密码子中的G:C至a: T突变和激活的N-ras基因，但在由相同致癌物治疗诱导的恶性肿瘤中，密码子61中的H-ras激活频率要低得多 (40%)。因此，DMBA在该系统中诱导了至少两种类型的遗传病变: H-ras激活 (存在于大多数退化的角膜瘤中) 和其他可能导致恶性肿瘤发展的未鉴定癌基因的激活。我们的观察结果表明，在该系统中，活化的H-ras基因的表达既不足以诱导恶性表型，甚至无法维持良性肿瘤的生长，并表明它可能与肿瘤消退有关。

BACKGROUND & AIMS: :Purpose: Recently, intraocular lidocaine anesthesia has been used in cataract surgery. We studied the toxicity of intraocular unpreserved lidocaine for corneal endothelial cell and retina using Japanese white rabbits.Methods: The rabbits were divided into two groups. One group was injected intracamerally and the other was injected intravitreally with 0.2 ml of unpreserved lidocaine of 0%, 0.02%, 0.2%, or 2% concentration. The number of corneal endothelial cells was measured 1 week after the injection. After measurements, the rabbit corneas were studied histologically. The retina was examined by electroretinogram prior to initial injection through 1 week after the injection.Results: There was no significant change in number of corneal endothelial cells after injection of 0.2% lidocaine. However, histological abnormality was seen in corneal endothelial cells after 2% lidocaine injection. There was also significant change in electroretinogram with 2% lidocaine injection. No histological abnormality was seen in the retina 1 week after the injection.Conclusion: The rabbit cornea and retina manifested no serious changes after the injection of lidocaine at less than 0.2% concentration functionally and histologically.

背景与目标： 目的: 最近，眼内利多卡因麻醉已用于白内障手术。我们使用日本大白兔研究了眼内未保存的利多卡因对角膜内皮细胞和视网膜的毒性。方法: 将兔子分为两组。一组在房内注射，另一组在玻璃体内注射未保存的0%，0.02%，0.2% 或2% 浓度的利多卡因0.2毫升。注射后1周测量角膜内皮细胞的数量。测量后，对兔角膜进行了组织学研究。在注射前至注射后1周，通过视网膜电图检查视网膜。结果: 注射0.2% 利多卡因后角膜内皮细胞数量无明显变化。然而，2% 利多卡因注射后角膜内皮细胞的组织学异常。2% 利多卡因注射液的视网膜电图也有显著变化。注射后1周，视网膜未见组织学异常。结论: 在功能和组织学上，注射低于0.2% 浓度的利多卡因后，兔角膜和视网膜无严重变化。