Altered feeding responses in mice with targeted disruption of the dopamine-3 receptor gene

Dopamine signaling has been implicated in the control of food intake and body weight. In particular, dopamine is important in the control of meal size and number and is thought to mediate the response to metabolic deprivation states. In the present experiments, the authors assessed the role of the dopamine-3 receptor (D3R) in the feeding responses to 2-deoxy-D-glucose, mercaptoacetate, and peripheral insulin. All 3 compounds increased food intake in wild-type mice, but the hyperphagic responses were blunted in D3R-/- mice. In other experiments, D3R-/- mice were hyperresponsive to the administration of amylin and leptin relative to wild-type mice. These results support the hypothesis that D3Rs chronically inhibit the effects of adiposity hormones, thereby contributing to a net anabolic state.     

Loss of heterozygosity and mutational analyses of the ACTRII gene locus in human colorectal tumors

The activin type II receptorgene (ACTRII) is mutated in 58.1% of microsatellite-unstable (MSI-H) colorectal cancers and is a close relative of the TGFbeta-1 type II receptor, which is known to be involved in both MSI-H and non-MSI-H colorectal carcinogenesis. We therefore sought to determine whether ACTRII was involved in non-MSI-H colorectal cancers. We evaluated ACTRII inactivation by allelic deletion, loss of mRNA expression, or somatic mutation in 51 non-MSI-H colon cancers. Loss of heterozygosity (LOH) at the ACTRII locus (2q23.1) was found in 9 (17.6%) of 51 primary tumors. Loss of ACTRII mRNA expression was seen in one (14.3%) of the seven LOH-positive primary tumors from which total RNA was available. We also performed DNA sequencing analysis of tumors showing LOH. One LOH-positive primary tumor exhibited a novel germline missense sequence alteration (amino acid substitution, 117 Ile to Phe) that was not found in 23 additional normal individuals, implying that this alteration is not a frequent polymorphism. We conclude that ACTRII is probably involved in both non-MSI-H and MSI-H colorectal carcinogenesis, but more frequently in the latter subgroup.     

Progressive osseous heteroplasia in the face of a child

We describe a rare case of progressive osseous heteroplasia of the face in a child. Biopsy showed osteoma cutis superficially with ectopic bone formation in the deeper tissues including skeletal muscle. Analysis of DNA from peripheral blood leukocytes showed mutations in the gene encoding the alpha subunit of the stimulatory G protein of adenylyl cyclase (GNAS1), confirming the diagnosis of progressive osseous heteroplasia.     

血脂测定结果的临床可接受性分析

目的:通过对不同检测系统血脂测定结果的偏倚评估,分析各系统间结果的可比性和临床可接受性。方法:参照CLSI文件相关要求,以可溯源的检测系统为目标检测系统,测定总胆固醇(TCH)、甘油三酯(TG)、载脂蛋白A1(APOA1)、载脂蛋白B(APOB)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C),对本院3个不同检测系统进行朗道质控物(水平2和水平3)各测定21次和测定新鲜血清标本40份。结果:朗道质控物和新鲜血清标本TCH、TG、APOA1、APOB、HDL-C、LDL-C浓度在系统间的差异均有显著性(P<0.05)。除LDL-C在各检测系统间的相关系数为0.7859~0.9259之间外,其他项目各系统间的相关系数均大于0.975。各检测系统测定TCH、TG的不精密度CV均小于5%,其他项目的不精密度CV均小于10%;以可溯源检测系统1为目标检测系统,临床可接受性能评价:TCH、LDL-C在检测系统2和检测系统3超出临床接受范围,HDL-C在检测系统2超出临床接受范围,其他项目临床均可接受。结论:3个不同检测系统测定TG、APOA1、APOB结果具有可比性;测定HDL-C结果具有部分可比性,TCH、LDL-C结果不具有可比性,需采取整改措施。     

Increased levels of endothelin-1 and differential endothelin type A and B receptor expression in scleroderma-associated fibrotic lung disease.

In addition to their vasoactive action, endothelins are potent peptides in the regulation of both cell proliferation and the turnover of extracellular matrix. Using immunohistochemical, autoradiographic, and molecular analyses, we have studied the localization and expression of endothelin-1 and endothelin A (ETA) and B (ETB) receptors in scleroderma-associated fibrotic lung disease. Increased ET-1 immunoreactivity was found in sclerotic tissue compared with control and was associated with the vasculature, pulmonary interstitium, and bronchial and alveolar epithelium. Microautoradiographic analysis after 125I-labeled ET-1 binding showed a two- to threefold increase in the expression of total ET-1 receptors in scleroderma lung tissue localized to the alveolar epithelium and the pulmonary interstitium which was composed of mainly fibroblastic cells with macrophages and some microvessels. RNAse protection assay revealed significantly reduced ETA receptor and slightly raised ETB message levels in systemic sclerosis lung. Surface expression of functional ET receptors was examined by targeted receptor blocking using mixed and receptor-subtype-selective ligands. A consistent decrease in ETA receptor binding sites was noted primarily within the interstitium and vasculature, in contrast to a slight increase in ETB receptors. Elevated ET-1 and the cell-specific pattern of endothelin receptor expression suggest that the endothelins may represent important mediators that influence the pathology of scleroderma-associated lung disease and other fibrotic conditions.     

小白鼠腘淋巴结淋巴窦的超微结构

我们观察了幼年小白鼠腘淋巴结淋巴窦的超微结构,窦壁由腔面向外一般出3层构成:(1)一层连续的内皮;(2)由一薄层细胞间质构成的基膜;(3)一层外膜网状细胞及其扁平的突起。内皮细胞核扁圆,异染色质细小,核仁不明显,胞质极薄,含粗面内质网极少,而有大量的吞饮小泡。细胞邻接处相互重叠或嵌合,有20nm宽的间隙相隔。有的地方可见不发达的细胞连接。当巨噬细胞或淋巴细胞穿越内皮时,可出现临时性间隙,内皮边缘与穿越细胞相贴。基膜由电子透明的无定形基质及细的胶原原纤维构成。外膜网状细胞的核异染色质较多,核仁明显,胞质丰富,含许多粗面内质网而很少吞饮小泡。外膜网状细胞之间常见0.5μm宽的间隙。在窦腔内有巨噬细胞、淋巴细胞及星状的网状细胞等。由于小白鼠腘淋巴结的淋巴窦小,故窦内星形的网状细胞很少,其超微结构特点,与外膜网状细胞及淋巴组织内的网状细胞相似,在突起的切面上,常见包有小束的胶原原纤维。巨噬细胞较多,形态不规则,常贴附于内皮细胞表面,核椭圆,常有凹陷,胞质丰富,含许多溶酶体。在取材前1h,于足垫注射中国墨汁的小鼠,巨噬细胞吞噬了大量粗的墨汁颗粒。本文认为,淋巴窦壁可能具有一定的屏障作用。     

Free electron laser induces specific immobilization of heparin on polysulfone films

Covalent immobilization of heparin has been developed to reduce the amount of heparin administered systematically during long-term dialysis. Recently, it was doubted partially because of the complexion during immobilization process. In this study, we investigated a novel method for specific immobilization of heparin on polysulfone (PSF) via free electron laser (FEL) irradiation. Laser wavelengths of 6.18 or 6.31 microm, the typical absorption bands of carboxyl groups of heparin and aromatic rings in PSF, respectively, were chosen to irradiate the thin heparin membrane formed on PSF surfaces. The amount of heparin immobilized on PSF was measured by the toluidine blue method. The binding of heparin on PSF was analyzed by X-ray photoelectron spectroscopy (XPS). The immobilization of heparin resulted in a hydrophilic surface on which decreased platelet adhesion was observed. The efficiency differences, depending on laser wavelengths, were discussed from the point of view of structural and environmental differences of light-absorbing groups.     

雷公藤多甙对佐剂性关节炎模型大鼠ICAM-1的影响

目的:探讨口服雷公藤多甙对大鼠佐剂性关节炎(adjuvant arthritis AA)的治疗作用,以及对外周淋巴器官中细胞黏附分子ICAM-1水平的影响.方法:制备大鼠AA模型,应用免疫组化法检测口服和未口服雷公藤多甙的大鼠淋巴器官中ICAM-1水平的变化;观察口服雷公藤多甙前后关节的肿胀度.结果:口服雷公藤多甙的AA大鼠的外周淋巴器官中ICAM-1的水平明显低于未口服雷公藤多甙的AA大鼠,关节炎症状明显改善.结论:口服雷公藤多甙可以有效降低ICAM-1水平,从而治疗佐剂性关节炎.     

NR2B反义寡核苷酸对脑缺血海马CA1区NR2BmRNA表达的影响

为研究NMDA受体2B亚单位(NR2B)反义寡核苷酸(antisense oligonucleotide to NR2B,ANR2B)对短暂性脑缺血后海马CA1区NR2B mRNA表达的影响,分别向成年SD大鼠海马CA1区内立体定位注射ANR2B、NR2B正义寡核苷酸(SNR2B)、无菌生理盐水(NS),或者插针不注射(NSNO),24h后行四动脉阻断前脑缺血手术(缺血15min、再灌注24h),经心冲灌固定取脑,连续冰冻切片,原位杂交组织化学方法染色,光镜下观察各组每侧鼠脑NR2B mRNA的表达变化,并用LEICAQWin进行图像分析。结果显示,单纯缺血组海马各区的NR2B mRNA显色强度明显增加;缺血再灌组、假手术组和正常组海马CA1区内ANR2B注射点及其周围的NR2B mRNA显色明显下降;而在注射SNR2B、NS或NSNO的各组海马切片上,NR2B mRNA显色均无明显变化。结果表明ANR2B可以特异性地在体局部防止缺血后NR2B mRNA的高水平表达。