BACKGROUND & AIMS: :The aim of this study was to examine the different patterns of cerebellar and/or brainstem atrophy in spinocerebellar ataxia (SCA) type 3 and 6. Eighteen patients (SCA3 n=9, SCA6 n=9) and 15 healthy volunteers were studied. Voxel-based morphometry (VBM) was applied to segmented grey matter (GM) and white matter (WM) of high-resolution T1-weighted brain volumes of each group. We found reduction of grey matter in the pons as well as in the vermis in SCA3 as compared to control subjects. In SCA6 significant grey matter loss was found in hemispheric lobules bilaterally as well as in the vermis. White matter analysis revealed significant changes in SCA3, especially in the pons, in the white matter surrounding the dentate nucleus (DN) and in the cerebellar peduncles, whereas no significant white matter reduction was found in SCA6 patients. Our results demonstrate different patterns of grey and white matter affection detected by magnetic resonance imaging (MRI) in SCA3 and SCA6 patients, confirming the pathological concept of cortical cerebellar atrophy in SCA6. In contrast, SCA3 represents a form of ponto-cerebellar atrophy with predominant affection of pontine nuclei and fibre tracts.

背景与目标： ：本研究的目的是检查3型和6型脊髓小脑共济失调（SCA）的小脑和/或脑干萎缩的不同模式。研究了18例患者（SCA3 n = 9，SCA6 n = 9）和15名健康志愿者。将基于体素的形态计量学（VBM）应用于每组高分辨率T1加权脑体积的分段灰质（GM）和白质（WM）。我们发现与对照组相比，SCA3的脑桥和s中的灰质减少。在SCA6中，在双侧的半球小叶以及在mis骨中都发现了明显的灰质损失。白质分析显示，SCA3的显着变化，尤其是在脑桥，齿状核（DN）周围的白质和小脑梗的脑桥中，特别是在脑桥中，而在SCA6患者中未发现显着的白质减少。我们的结果表明，在SCA3和SCA6患者中通过磁共振成像（MRI）检测到不同的灰白色和白色物质影响模式，证实了SCA6皮质小脑萎缩的病理学概念。相反，SCA3代表了一种桥脑小脑萎缩的形式，主要影响桥脑核和纤维束。

BACKGROUND & AIMS: The Dlx homeobox gene family is expressed in a complex pattern within the embryonic craniofacial ectoderm and ectomesenchyme. A previous study established that Dlx-2 is essential for development of proximal regions of the murine first and second branchial arches. Here we describe the craniofacial phenotype of mice with mutations in Dlx-1 and Dlx-1 and -2. The skeletal and soft tissue analyses of mice with Dlx-1 and Dlx-1 and -2 mutations provide additional evidence that the Dlx genes regulate proximodistal patterning of the branchial arches. This analysis also elucidates distinct and overlapping roles for Dlx-1 and Dlx-2 in craniofacial development. Furthermore, mice lacking both Dlx-1 and -2 have unique abnormalities, including the absence of maxillary molars. Dlx-1 and -2 are expressed in the proximal and distal first and second arches, yet only the proximal regions are abnormal. The nested expression patterns of Dlx-1, -2, -3, -5, and -6 provide evidence for a model that predicts the region-specific requirements for each gene. Finally, the Dlx-2 and Dlx-1 and -2 mutants have ectopic skull components that resemble bones and cartilages found in phylogenetically more primitive vertebrates.

背景与目标： Dlx同源盒基因家族以复杂的模式在胚胎颅面外胚层和外间质内表达。先前的研究表明，Dlx-2对于鼠的第一和第二分支弓近端区域的发育至关重要。在这里，我们描述了具有Dlx-1和Dlx-1和-2突变的小鼠的颅面表型。具有Dlx-1和Dlx-1和-2突变的小鼠的骨骼和软组织分析提供了其他证据，证明Dlx基因调节branch弓的近现代模式。该分析还阐明了Dlx-1和Dlx-2在颅面发育中的独特作用和重叠作用。此外，缺乏Dlx-1和-2的小鼠具有独特的异常，包括不存在上颌磨牙。 Dlx-1和-2在近端和远端第一和第二弓形中表达，但仅近端区域异常。 Dlx-1，-2，-3，-5和-6的嵌套表达模式为预测每个基因的区域特定要求的模型提供了证据。最后，Dlx-2，Dlx-1和-2突变体具有异位的头骨成分，类似于在系统发育上较原始的脊椎动物中发现的骨骼和软骨。

BACKGROUND & AIMS: :Hepatic steatosis is defined by an increased content of hepatocellular lipids (HCLs) and is frequently observed in insulin-resistant states including type 2 diabetes mellitus. A dietary excess of saturated fat contributes significantly to HCL accumulation. Elevated HCL levels mainly account for hepatic insulin resistance, which is probably mediated by partitioning of free fatty acids to the liver (fat overflow) and by an imbalance of adipocytokines (decreased adiponectin and/or increased proinflammatory cytokines). Both free fatty acids and adipocytokines activate inflammatory pathways that include protein kinase C, the transcription factor nuclear factor kappaB, and c-Jun N-terminal kinase 1 and can thereby accelerate the progression of hepatic steatosis to nonalcoholic steatohepatitis and cirrhosis. Proton magnetic resonance spectroscopy has made it possible to quantify HCL concentrations and to detect even small changes in these concentrations in clinical settings. Moderately hypocaloric, fat-reduced diets can decrease HCL levels by approximately 40-80% in parallel with loss of up to 8% of body weight. Treatment with thiazolidinediones (e.g. pioglitazone and rosiglitazone) reduces HCL levels by 30-50% by modulating insulin sensitivity and endocrine function of adipose tissue in type 2 diabetes. Metformin improves hepatic insulin action without affecting HCL levels, whereas insulin infusion for 67 h increases HCL levels by approximately 18%; furthermore, HCL levels positively correlate with the insulin dosage in insulin-treated type 2 diabetes. In conclusion, liver fat is a critical determinant of metabolic fluxes and inflammatory processes, thereby representing an important therapeutic target in insulin resistance and type 2 diabetes mellitus.

背景与目标： 肝脂肪变性是由肝细胞脂质（HCL）含量增加所定义的，并且经常在包括2型糖尿病在内的胰岛素抵抗状态中观察到。饮食中饱和脂肪过多会大大增加HCL的积累。 HCL水平升高主要是肝脏胰岛素抵抗的原因，这可能是由于游离脂肪酸在肝脏中的分配（脂肪溢出）和脂肪细胞因子的失衡（脂联素减少和/或促炎性细胞因子增加）引起的。游离脂肪酸和脂肪细胞因子均激活包括蛋白激酶C，转录因子核因子kappaB和c-Jun N端激酶1在内的炎症途径，从而可以加速肝脂肪变性发展为非酒精性脂肪性肝炎和肝硬化。质子磁共振波谱使量化HCL浓度和检测临床环境中这些浓度的微小变化成为可能。适度低热量，低脂肪饮食可将HCL水平降低约40-80％，同时最多可减少8％的体重。噻唑烷二酮类药物（例如吡格列酮和罗格列酮）治疗可通过调节2型糖尿病的胰岛素敏感性和脂肪组织的内分泌功能将HCL水平降低30-50％。二甲双胍在不影响HCL水平的情况下改善了肝胰岛素的作用，而胰岛素输注67 h使HCL水平增加了约18％。此外，在用胰岛素治疗的2型糖尿病中，HCL水平与胰岛素剂量呈正相关。总之，肝脏脂肪是代谢通量和炎症过程的关键决定因素，因此代表了胰岛素抵抗和2型糖尿病的重要治疗靶标。

BACKGROUND & AIMS: Pilomatricoma is a distinctive tumor characterized by a dual population of proliferating basophilic cells and diagnostic shadow cells, believed to arise from the hair matrix. The normal hair matrix undergoes defined cycles of growth (anagen), regression (catagen), and resting (telogen) that are regulated by programmed cell death (apoptosis). bcl-2 is a proto-oncogene that helps to suppress apoptosis in both benign and malignant tumors. In addition, both apoptosis and bel-2 are critical factors in normal hair follicle development. In order to clarify the role of bcl-1, we used immunohistochemical means to study 10 cases of histologically proven pilomatricoma for bcl-2 expression. The study design included both positive and negative controls. All of the pilomatricomas in our series were strongly decorated by bcl-2 immunostaining. Based on our findings of increased bcl-2 staining, we concluded that the faulty suppression of apoptosis contributes to the pathogenesis of pilomatricoma.

背景与目标： 口唇瘤是一种独特的肿瘤，其特征是增殖的嗜碱性细胞和诊断性影子细胞由双重人群组成，据信它们是由毛发基质引起的。正常的头发基质会经历特定的生长（生长期），消退（退化期）和静止（休止期）周期，这些周期受程序性细胞死亡（细胞凋亡）的调节。 bcl-2是一种原癌基因，有助于抑制良性和恶性肿瘤中的细胞凋亡。此外，凋亡和bel-2都是正常毛囊发育的关键因素。为了阐明bcl-1的作用，我们使用免疫组化方法研究了10例经组织学证实的pilomatricoma的bcl-2表达。研究设计包括阳性和阴性对照。 bcl-2免疫染色强烈修饰了我们系列中的所有pilomatricomas。根据bcl-2染色增加的发现，我们得出结论，凋亡的错误抑制是导致毛细血管瘤的发病原因。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: The GATA family of vertebrate DNA binding regulatory proteins are expressed in diverse tissues and at different times of development. However, the DNA binding regions of these proteins possess considerable homology and recognize a rather similar range of DNA sequence motifs. DNA binding is mediated through two domains, each containing a zinc finger. Previous results have led to the conclusion that although in some cases the N-terminal finger can contribute to specificity and strength of binding, it does not bind independently, whereas the C-terminal finger is both necessary and sufficient for binding. Here we show that although this is true for the N-terminal finger of GATA-1, those of GATA-2 and GATA-3 are capable of strong independent binding with a preference for the motif GATC. Binding requires the presence of two basic regions located on either side of the N-terminal finger. The absence of one of these near the GATA-1 N-terminal finger probably accounts for its inability to bind. The combination of a single finger and two basic regions is a new variant of a motif that has been previously found in the binding domains of other finger proteins. Our results suggest that the DNA binding properties of the N-terminal finger may help distinguish GATA-2 and GATA-3 from GATA-1 and the other GATA family members in their selective regulatory roles in vivo.

背景与目标： GATA家族的脊椎动物DNA结合调节蛋白在不同的组织中以及在不同的发育时期表达。但是，这些蛋白质的DNA结合区具有相当的同源性，可以识别相当相似范围的DNA序列基序。 DNA结合是通过两个结构域介导的，每个结构域都包含一个锌指。先前的结果得出的结论是，尽管在某些情况下N末端指可以有助于结合的特异性和强度，但它不能独立地结合，而C末端指对于结合既是必需的又是足够的。在这里，我们表明，尽管对于GATA-1的N端手指来说确实如此，但GATA-2和GATA-3的手指却能够强烈独立地结合，并优先选择基序GATC。结合需要在N末端指形物的两侧都存在两个基本区域。在GATA-1 N端手指附近缺少这些手指之一可能是其无法结合的原因。单个手指和两个基本区域的组合是一个基序的新变体，该变体先前已在其他手指蛋白的结合域中发现。我们的结果表明，N末端手指的DNA结合特性可能有助于区分GATA-2和GATA-3与GATA-1和其他GATA家族成员在体内的选择性调节作用。

BACKGROUND & AIMS: :Our objective was to follow the course of a dysmyelinating disease followed by partial recovery in transgenic mice using non-invasive high-resolution (117 x 117 x 70 microm) magnetic resonance (microMRI) and evoked potential of the visual system (VEP) techniques. We used JOE (for J37 golli overexpressing) transgenic mice engineered to overexpress golli J37, a product of the Golli-mbp gene complex, specifically in oligodendrocytes. Individual JOE transgenics and their unaffected siblings were followed from 21 until 75-days-old using non-invasive in vivo VEPs and 3D T2-weighted microMRI on an 11.7 T scanner, performing what we believe is the first longitudinal study of its kind. The microMRI data indicated clear, global hypomyelination during the period of peak myelination (21-42 days), which was partially corrected at later ages (>60 days) in the JOE mice compared to controls. These microMRI data correlated well with [Campagnoni AT (1995) "Molecular biology of myelination". In: Ransom B, Kettenmann H (eds) Neuroglia--a Treatise. Oxford University Press, London, pp 555-570] myelin staining, [Campagnoni AT, Macklin WB (1988) Cellular and molecular aspects of myelin protein gene-expression. Mol Neurobiol 2:41-89] a transient intention tremor during the peak period of myelination, which abated at later ages, and [Lees MB, Brostoff SW (1984) Proteins in myelin. In: Morell (ed) Myelin. Plenum Press, New York and London, pp 197-224] VEPs which all indicated a significant delay of CNS myelin development and persistent hypomyelination in JOE mice. Overall these non-invasive techniques are capable of spatially resolving the increase in myelination in the normally developing and developmentally delayed mouse brain.

背景与目标： ：我们的目标是通过非侵入性高分辨率（117 x 117 x 70 microm）磁共振（microMRI）和诱发视觉系统（VEP）技术追踪转基因小鼠的运动异常，然后部分恢复。我们使用经工程改造过表达Golli-mbp基因复合物产物Golli J37（特别是在少突胶质细胞中）的JOE（用于J​​37 golli过表达）转基因小鼠。从21岁到75天大，使用11.7 T扫描仪上的非侵入性体内VEP和3D T2加权显微MRI对个体JOE转基因及其未受影响的兄弟姐妹进行跟踪研究，我们认为这是同类研究中的首次纵向研究。显微MRI数据表明，在峰值髓鞘形成期（21-42天）期间出现了明显的整体性低髓鞘形成，与对照组相比，JOE小鼠在以后的年龄（> 60天）中得到了部分纠正。这些显微MRI数据与[Campagnoni AT（1995）“髓鞘形成的分子生物学”）有很好的相关性。在：Ransom B，Kettenmann H（eds）Neuroglia-专着中。牛津大学出版社，伦敦，第555-570页]髓磷脂染色，[Campagnoni AT，Macklin WB（1988）髓磷脂蛋白基因表达的细胞和分子方面。 [Mol Neurobiol 2：41-89]在髓鞘形成高峰期发生短暂的意向性震颤，此现象在以后的年龄有所减轻，[Lees MB，Brostoff SW（1984）Proteins in髓磷脂。在：莫雷尔（编辑）髓磷脂。 [Plenum Press，纽约和伦敦，第197-224页] VEP均表明JOE小鼠的CNS髓磷脂发育显着延迟和持续性髓鞘减少。总体而言，这些非侵入性技术能够在空间上解决正常发育和发育迟缓的小鼠大脑中髓鞘形成的增加。