北方汉族人群维生素D受体基因Bsm I位点多态性与前列腺癌易感性的相关性分析

目的 :研究低发病的中国汉族人群维生素D受体基因 (VDRG)BsmⅠ 位点单核苷酸多态性 (SNP)与前列腺癌的关系 ,探讨不同种族前列腺癌发病的基因差异。　方法 :收集中国北方地区汉族人群 10 3例前列腺癌病人及10 6例健康对照者外周血标本 ,应用变性高效液相色谱 (DHPLC)检测VDRG第 8内含子BsmⅠ多态位点 ,并对该位点SNP分布进行分析。　结果 :BsmⅠ 多态位点bb、Bb、BB基因型和等位基因在北方地区汉族前列腺癌病人及对照者中的分布频率差异无显著性 (P >0 .0 5 ) ,基因型分布频率分别为 92 .2 3%、7.77%、0和 94.34 %、5 .6 6 %、0 ;等位基因B、b分别为 3.88%、96 .12 %和 2 .91%、97.0 9%,而与高发病人群的分布相比有显著不同。　结论 :VDRGBsmⅠ多态性在低发病的中国汉族人群与前列腺癌无相关 ,其分布与高发病人群有明显差异 ,提示VDRGBsmⅠ多态性可能是前列腺癌发病种族差异的原因之一。     

Postnatal dendritic development of Y-like geniculocortical relay neurons.

We describe the dendritic development of neurons in the dorsal lateral geniculate nucleus (LGNd) projecting to cortical area 18 in the postnatal cat. LGN neurons were identified by retrograde labeling from area 18 with fluorescent latex microspheres and injected in the fixed slice with Lucifer yellow (LY) and horseradish peroxidase (HRP) to visualize their dendritic arborizations. Both topological (measures of the patterns of dendritic branching and their territorial coverage) and metric parameters (measures of the quantitative parameters describing the size, length, extent and diameter of the dendritic arbors) were measured in three-dimensions for 25 LGN neurons in cats between 1 and 18 postnatal weeks. In addition, dendritic growth was compared to the changing dimensions of the LGNd. At all ages, neurons projecting to area 18 have large somata and radiate dendrites. From 1 to 18 weeks neurons increase in size--both soma area and the length of all dendritic segments double during this period. Intermediate and terminal dendritic segments show comparable growth until 5 weeks. However, only terminal segments continue to grow significantly from 5 until 18 weeks. Dendrites become straighter during development, the angle between daughter branches decreases and dendritic segment diameter increases, with terminal segments showing a greater increase relative to intermediate segments. The density of dendritic appendages increases transiently at 5 weeks and a differential redistribution occurs, so that by 18 weeks dendrites further from the soma have a greater density of appendages than those near the soma. Some dendritic relationships remain invariant during development--intermediate segments are always shorter, thicker and straighter than terminal segments. During these changes however, area 18 projecting neurons maintain a constant number of primary dendrites and have, on average, a constant branching pattern. The relative volume of the LGNd occupied by an area 18 projecting neuron increases 2.4-fold between 1 and 18 weeks as the dendrites grow with the result that the coverage of a given point of the LGNd by dendrites of area 18 projecting nearly doubles from 24 to 45 neurons per unit volume. This increased net dendritic overlap provides a substrate for enhanced numerical synaptic divergence of the Y-cell pathway from a point source in the retina to the visual cortex.     

Initial results of a phase I trial of continuous infusion SR 2508 (etanidazole): a radiation therapy oncology group study

To exploit both the oxygen-mimetic and "pre-incubation" or continuous exposure effects of the 2-nitroimidazole radiosensitizers, we are conducting a Phase I trial of continuous infusion SR 2508 for patients receiving brachytherapy. Following the administration of a loading dose of 2 g/m2, SR 2508 is administered by continuous infusion for 48 hr. Twenty-one patients have completed treatment. The initial total dose was 8 g/m2 with patients currently receiving 15 g/m2. No toxicity has been observed. At the higher doses the steady-state plasma concentrations have been between 50 and 70 micrograms/ml. It is not yet known whether or not hypoxic sensitizers will be of benefit clinically, and if so, when during a course of treatment is the optimal time to use them. Given the lack of toxicity and plasma concentrations achievable with continuous infusion, future studies will be conducted using SR 2508 during both the external beam and brachytherapy aspects of treatment.     

Evaluation of the differentiation potential of WB-F344 rat liver epithelial stem-like cells in vivo. Differentiation to hepatocytes after transplantation into dipeptidylpeptidase-IV-deficient rat liver.

After intrahepatic transplantation into livers of adult syngeneic German-strain Fischer 344 rats that are deficient for the bile canalicular enzyme dipeptidyl peptidase IV (DPP-IV), cultured WB-F344 rat liver epithelial cells (without exogenous marker genes) integrate into hepatic plates and differentiate into hepatocyte-like cells that are morphologically and functionally indistinguishable from mature hepatocytes. In this model system, the differentiated progeny of transplanted WB-F344 cells are identified among the DPP-IV-negative host hepatocytes by their expression of bile canalicular DPP-IV enzyme activity. DPP-IV-positive hepatocyte-like cells also expressed other markers of hepatocytic differentiation, including albumin, transferrin, and alpha-1-antitrypsin, suggesting that the progeny of transplanted WB-F344 cells express a complete hepatocyte differentiation program. These results complement our previous studies indicating WB-F344 cells can serve as stem-like precursor cells for differentiated hepatocytes and strengthen the suggestion that WB-F344 rat liver epithelial cells represent the cultured counterpart of liver stem-like hepatocyte progenitor cells present in the normal adult rat liver.     

Hemin-binding surface protein from Bartonella quintana

Bartonella quintana, the agent of trench fever and a cause of endocarditis and bacillary angiomatosis in humans, has the highest reported in vitro hemin requirement for any bacterium. We determined that eight membrane-associated proteins from B. quintana bind hemin and that a approximately 25-kDa protein (HbpA) was the dominant hemin-binding protein. Like many outer membrane proteins, HbpA partitions to the detergent phase of a Triton X-114 extract of the cell and is heat modifiable, displaying an apparent molecular mass shift from approximately 25 to 30 kDa when solubilized at 100 degrees C. Immunoblots of purified outer and inner membranes and immunoelectron microscopy with whole cells show that HbpA is strictly located in the outer membrane and surface exposed, respectively. The N-terminal sequence of mature HbpA was determined and used to clone the HbpA-encoding gene (hbpA) from a lambda genomic library. The hbpA gene is 816 bp in length, encoding a predicted immature protein of approximately 29.3 kDa and a mature protein of 27.1 kDa. A Fur box homolog with 53% identity to the Escherichia coli Fur consensus is located upstream of hbpA and may be involved in regulating expression. BLAST searches indicate that the closest homologs to HbpA include the Bartonella henselae phage-associated membrane protein, Pap31 (58.4% identity), and the OMP31 porin from Brucella melitensis (31.7% identity). High-stringency Southern blots indicate that all five pathogenic Bartonella spp. possess hbpA homologs. Recombinant HbpA can bind hemin in vitro; however, it does not confer a hemin-binding phenotype upon E. coli. Intact B. quintana treated with purified anti-HbpA Fab fragments show a significant (P < 0.004) dose-dependent decrease in hemin binding relative to controls, suggesting that HbpA plays an active role in hemin acquisition and therefore pathogenesis. HbpA is the first potential virulence determinant characterized from B. quintana.