Health-related worries, self-image, and life outlooks of long-term survivors of childhood cancer.

This article poses three questions: what do childhood cancer survivors worry about? What characteristics prompt some to worry more and others less? What effect do worries have on survivors' self-image and life outlooks? Data from 303 survivors of childhood cancer demonstrated significant relationships among worries, "objective" factors like physical after-effects or relapse, and survivors' self-images and life outlooks. However, findings also indicated that subjectively experienced worries, perceptions about one's cancer status, age at diagnosis and gender were more strongly associated with self-image and life outlook. Psychosocial interventions andfuture research are suggested.     

Combined diffusion-weighted and perfusion-weighted flow heterogeneity magnetic resonance imaging in acute stroke

BACKGROUND AND PURPOSE: The heterogeneity of microvascular flows is known to be an important determinant of the efficacy of oxygen delivery to tissue. Studies in animals have demonstrated decreased flow heterogeneity (FH) in states of decreased perfusion pressure. The purpose of the present study was to assess microvascular FH changes in acute stroke with use of a novel perfusion-weighted MRI technique and to evaluate the ability of combined diffusion-weighted MRI and FH measurements to predict final infarct size. METHODS: Cerebral blood flow, FH, and plasma mean transit time (MTT) were measured in 11 patients who presented with acute (<12 hours after symptom onset) stroke. Final infarct size was determined with follow-up MRI or CT scanning. RESULTS: In normal brain tissue, the distribution of relative flows was markedly skewed toward high capillary flow velocities. Within regions of decreased cerebral blood flow, plasma MTT was prolonged. Furthermore, subregions were identified with significant loss of the high-flow component of the flow distribution, thereby causing increased homogeneity of flow velocities. In parametric maps that quantify the acute deviation of FH from that of normal tissue, areas of extreme homogenization of capillary flows predicted final infarct size on follow-up scans of 10 of 11 patients. CONCLUSIONS: Flow heterogeneity and MTT can be rapidly assessed as part of a routine clinical MR examination and may provide a tool for planning of individual stroke treatment, as well as in targeting and evaluation of emerging therapeutic strategies.     

Comparison of vasa vasorum after intravascular stent placement with sirolimis drug‐eluting and bare metal stents

The cytostatic drug, sirolimis has shown prevention in neointimal hyperplasia after stent placement. Recent studies have shown persistent inflammation seen with drug‐eluting stents (DES) may result in late stent thrombosis. The aim of this study is to compare effects of bare metal stents (BMS) and sirolimis DES on the neointima and vasa vasorum in stented rabbit aortas. Stents were implanted in eight New Zealand rabbits for 9 weeks. Group I rabbits received BMS. Group II rabbits received sirolimis DES. A balloon‐mounted BMS or DES was placed in the infrarenal aorta. Following euthanasia, aortas were perfused with barium sulfate and sectioned for histology. After 9 weeks the qualitative intrastent luminal diameter was fairly uniform in both the DES and the BMS. The thickness of neointima was similar in both groups. The number of vasa vasorum in the sirolimis DES increased compared with the BMS (P < 0.05). An increased number of vasa vasorum produced by the DES when compared with the BMS shows a difference in response to local vessel injury in rabbits. This result suggests that vasa vasorum may play a role in the persistent inflammation generated by sirolimis‐coated stents.     

Chemotherapy-Induced Apoptosis in a Transgenic Model of Neuroblastoma Proceeds Through p53 Induction

Chemoresistance in neuroblastoma is a significant issue complicating treatment of this common pediatric solid tumor. MYCN-amplified neuroblastomas are infrequently mutated at p53 and are chemosensitive at diagnosis but acquire p53 mutations and chemoresistance with relapse. Paradoxically, Myc-driven transformation is thought to require apoptotic blockade. We used the TH-MYCN transgenic murine model to examine the role of p53-driven apoptosis on neuroblastoma tumorigenesis and the response to chemotherapy. Tumors formed with high penetrance and low latency in p53-haploinsufficient TH-MYCN mice. Cyclophosphamide (CPM) induced a complete remission in p53 wild type TH-MYCN tumors, mirroring the sensitivity of childhood neuroblastoma to this agent. Treated tumors showed a prominent proliferation block, induction of p53 protein, and massive apoptosis proceeding through induction of the Bcl-2 homology domain-3-only proteins PUMA and Bim, leading to the activation of Bax and cleavage of caspase-3 and -9. Apoptosis induced by CPM was reduced in p53-haploinsufficient tumors. Treatment of MYCN-expressing human neuroblastoma cell lines with CPM induced apoptosis that was suppressible by siRNA to p53. Taken together, the results indicate that the p53 pathway plays a significant role in opposing MYCN-driven oncogenesis in a mouse model of neuroblastoma and that basal inactivation of the pathway is achieved in progressing tumors. This, in part, explains the striking sensitivity of such tumors to chemotoxic agents that induce p53-dependent apoptosis and is consistent with clinical observations that therapy-associated mutations in p53 are a likely contributor to the biology of tumors at relapse and secondarily mediate resistance to therapy.     

Trinucleotide repeats in the human genome: size distributions for all possible triplets and detection of expanded disease alleles in a group of Huntington disease individuals by the repeat expansion detection method

Using a modified Repeat Expansion Detection (RED) assay, that was optimized for individual oligonucleotides, unrelated individuals were systematically screened for maximal repeat sizes of each of the ten possible trinucleotide repeats. Cloned trinucleotide repeats were generated and used as standards for the detectability of single copy trinucleotide repeat fragments. When the size distributions of trinucleotide repeats were compared to previously reported data, significant differences were found for the CTT repeat, which corresponds to the expanded GAA repeat in Friedreich ataxia, as well as for ATT, CCT and GTT repeats. Since 30-35% of normal individuals have CTG/CAG trinucleotide repeat sizes of 180 bp or more, we investigated the question whether small-scale CTG/CAG repeat expansions are detectable on a population basis by using the RED technique. We blindly screened 20 HD probands with CAG expansions of the HD gene, ranging in size between 120 and 174 bp, and found that a shift to larger CAG size ranges is clearly detectable when comparing the distribution of maximal repeat sizes in the disease group to a control group. Our study, therefore, demonstrates that the application of the RED assay to a population of probands and a population of controls allows the detection of small-scale CTG/CAG repeat expansions in the size range of the expanded HD gene and present in a single allele. We also provide standards and control data for the detection of other trinucleotide repeat expansions.      

Interleukin-33 Promotes Serotonin Release from Enterochromaffin Cells for Intestinal Homeostasis

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mRNA差异显示法筛选和克隆胎肝中差异表达基因

0　引言　胎肝正处于生长发育阶段 ,其中表达的一些基因在成人肝脏中处于关闭状态 ,当成人肝脏部分切除或肝细胞广泛受损时 ,剩余肝细胞表现出很强的再生能力 ,再生成年肝脏和肝癌细胞中都出现有发育早期基因的表达 [1 ] .克隆这类胎肝中差异表达的基因 ,将有助于了解肝脏的发育过程 ,并为肝脏再生及肝脏相关疾病的研究提供线索 .1　材料和方法1.1　材料　胎肝和成人肝组织分别由西京医院妇产科和肝胆外科提供 .差示 PCR引物为 5′端 10碱基随机引物 I(RPI) :5′- AGCCACCATG- 3′ ;5′端 10碱基随机引物 II(RPII) :5′- TAGCAG…