腺病毒载体介导的PML生长抑制因子对前列腺癌细胞生长和致瘤能力的抑制效果

为探讨用腺病毒载体携带ＰＭＬ（ＰｒｏｍｙｅｌｏｃｙｔｉｃＬｅｕｋｅｍｉａ）基因作为前列腺癌基因治疗的可能性，应用重组人携带ＰＭＬ基因腺病毒（ＡｄＰＭＬ）感染培养的前列腺癌细胞，观察表达ＰＭＬ蛋白的癌细胞与对照组癌细胞的体外生长和裸鼠体内致瘤能力变化，对荷瘤裸鼠瘤体周围注射ＡｄＰＭＬ，观察治疗组和对照组肿瘤生长的变化。结果显示，感染ＡｄＰＭＬ的前列腺癌细胞体外生长和裸鼠体内致瘤能力明显下降，荷瘤裸鼠瘤体周围注射ＡｄＰＭＬ后肿瘤生长速度明显减慢。证实了ＰＭＬ是一种生长抑制因子，提示其可能被应用于前列腺癌的基因治疗研究     

Evaluation of a Metal Artifacts Reduction Algorithm Applied to Postinterventional Flat Panel Detector CT Imaging

BACKGROUND AND PURPOSE:Flat panel detector CT images are degraded by streak artifacts caused by radiodense implanted materials such as coils or clips. A new metal artifacts reduction prototype algorithm has been used to minimize these artifacts. The application of this new metal artifacts reduction algorithm was evaluated for flat panel detector CT imaging performed in a routine clinical setting.MATERIALS AND METHODS:Flat panel detector CT images were obtained from 59 patients immediately following cerebral endovascular procedures or as surveillance imaging for cerebral endovascular or surgical procedures previously performed. The images were independently evaluated by 7 physicians for metal artifacts reduction on a 3-point scale at 2 locations: immediately adjacent to the metallic implant and 3 cm away from it. The number of visible vessels before and after metal artifacts reduction correction was also evaluated within a 3-cm radius around the metallic implant.RESULTS:The metal artifacts reduction algorithm was applied to the 59 flat panel detector CT datasets without complications. The metal artifacts in the reduction-corrected flat panel detector CT images were significantly reduced in the area immediately adjacent to the implanted metal object (P = .05) and in the area 3 cm away from the metal object (P = .03). The average number of visible vessel segments increased from 4.07 to 5.29 (P = .1235) after application of the metal artifacts reduction algorithm to the flat panel detector CT images.CONCLUSIONS:Metal artifacts reduction is an effective method to improve flat panel detector CT images degraded by metal artifacts. Metal artifacts are significantly decreased by the metal artifacts reduction algorithm, and there was a trend toward increased vessel-segment visualization.

With continued technologic developments, both diagnostic and interventional neuroendovascular applications of flat panel detector CT (FDCT) have increasingly expanded. FDCT offers higher spatial resolution relative to multidetector row CT and improved visualization of clipped aneurysms and endovascular stents.¹ Imaging performed in the endovascular suite also offers rapid visualization of periprocedural complications, thus allowing faster management.² The acquired FDCT images, however, are degraded by artifacts created by radiodense cerebral endovascular and surgical implants including coils, stents, and clips, limiting the use of FDCT as a postprocedural imaging technique.Metal artifacts reduction (MAR) in CT images has been attempted by both interpolation and algebraic methods. Interpolation methods have been quite successful and, most important, require less computational power relative to algebraic methods, resulting in less computing time. One of the first interpolation-based MAR algorithms used a 1D linear interpolation for single-row CT data, which is inadequate for FDCT data.³ The MAR algorithm investigated in this work, developed by Siemens Healthcare Sector, is a modification and extension of a recently published MAR procedure by Prell et al.⁴ We present validation of the FDCT MAR prototype algorithm by using a phantom study and an objective critique by 7 clinicians.     

Generation of CD1+RelB+ dendritic cells and tartrate-resistant acid phosphatase-positive osteoclast-like multinucleated giant cells from human monocytes

We previously showed that granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF) stimulate the differentiation of human monocytes into two phenotypically distinct types of macrophages. However, in vivo, not only CSF but also many other cytokines are produced under various conditions. Those cytokines may modulate the differentiation of monocytes by CSFs. In the present study, we showed that CD14+ adherent human monocytes can differentiate into CD1+relB+ dendritic cells (DC) by the combination of GM-CSF plus interleukin-4 (IL-4) and that they differentiate into tartrate-resistant acid phosphatase (TRAP)-positive osteoclast-like multinucleated giant cells (MGC) by the combination of M-CSF plus IL-4. However, the monocyte-derived DC were not terminally differentiated cells; they could still convert to macrophages in response to M-CSF. Tumor necrosis factor-alpha (TNF-alpha) stimulated the terminal differentiation of the DC by downregulating the expression of the M-CSF receptor, cfms mRNA, and aborting the potential to convert to macrophages. In contrast to IL-4, interferon-gamma (IFN-gamma) had no demonstrable effect on the differentiation of monocytes. Rather, IFN- gamma antagonized the effect of IL-4 and suppressed the DC and MGC formation induced by GM-CSF + IL-4 and M-CSF + IL-4, respectively. Taken together, these results provide a new aspect to our knowledge of monocyte differentiation and provide evidence that human monocytes are flexible in their differentiation potential and are precursors not only of macrophages but also of CD1+relB+DC and TRAP-positive MGC. Such a diverse pathway of monocyte differentiation may constitute one of the basic mechanisms of immune regulation.     

Factor VIII-von Willebrand factor requires calcium for facilitation of platelet adherence

The role of divalent cations in platelet adherence to deendothelialized human arteries in flowing blood was investigated in an annular perfusion chamber. Spreading of platelets on the subendothelium was impaired below 30 microM of free Ca2+ ions (Ca2+). When Ca2+ was replaced by Mg2+, adherence was unchanged in perfusates without exogenous factor VIII-von Willebrand factor (FVIII-vWF), but the ability of FVIII-vWF to support platelet adherence was lost. Binding of FVIII-vWF to the vessel wall was independent of divalent cations, but bound FVIII-vWF was only able to mediate adherence after exposure to Ca2+. Pretreatment of FVIII-vWF with the calcium chelator EGTA (10 mM) resulted in loss of the ability to facilitate platelet adherence, while the ristocetin cofactor activity remained intact. Full restoration of the ability to mediate platelet adherence could only be obtained by prolonged dialysis against Ca2+ in the millimolar range. These data indicate that divalent cations have at least two separate roles to play in supporting platelet adherence: (1) platelet spreading on the subendothelium requires Ca2+ or Mg2+; (2) FVIII-vWF should be exposed to Ca2+ to obtain its optimal biologic activity in supporting platelet adherence.     

Effects of positive and negative pressure ventilation on cerebral blood volume of newborn infants

The effects of intermittent positive airway and continuous negative extrathoracic pressure ventilation on cerebral blood volume in preterm infants were studied using near infrared spectroscopy. In 12 infants continuous negative extrathoracic pressure caused a median decrease in cerebral blood volume of 0.14ml/100ml brain (95% confidence intervals (CI) 0.035–0.280) compared with no respiratory support. Oxygenated and deoxygenated haemoglobin also decreased, implying increased venous drainage as the main effect. In 17 infants intermittent positive pressure ventilation also caused a median reduction in cerebral blood volume of 0.06 ml/100 ml brain (95% CI 0.010–0.115) compared with endotracheal positive airway pressure. Deoxygenated haemoglobin increased by 0.07 ml/100 ml brain (95% CI 0.010–0.100) while oxygenated haemoglobin decreased by O.lOml/lOOml brain (95% CI 0.005–0.175). The increase in deoxygenated haemoglobin implies decreased venous drainage and the decrease in oxygenated haemoglobin implies that other factors may also be significant. Heart rate, blood pressure and oxygen saturation were monitored continuously and remained stable.     

Sensitivity of Escherichia coli (MutT) and human (MTH1) 8-oxo-dGTPases to in vitro inhibition by the carcinogenic metals, nickel(II), copper(II), cobalt(II) and cadmium(II)

The toxicity of Ni(II), Co(II) and Cu(II) in animals, and that of Cd(II) in cultured cells, has been associated with generation of the promutagenic lesion 8-oxo-7,8-dihydroguanine (8-oxoguanine) in DNA, among other effects. One possible source of this base may be 8-oxo-7,8- dihydro-2'-deoxyguanosine-5'-triphosphate (8-oxo-dGTP), a product of oxidative damage to the nucleotide pool, from which it is incorporated into DNA. To promote such incorporation, the metals would have to inhibit specific cellular 8-oxo-dGTPases that eliminate 8-oxo-dGTP from the nucleotide pool. The present study was designed to test such inhibition in vitro on 8-oxo-dGTPases from two different species, the human MTH1 protein and Escherichia coli MutT protein. In the presence of Mg(II), the natural activator of 8-oxo-dGTPases, all four metals were found to inhibit both enzymes. For MTH1, the IC50 values (+/- SE; n = 3-4) were 17 +/- 2 microM for Cu(II), 30 +/- 8 microM for Cd(II), 376 +/- 71 microM for Co(II) and 801 +/- 97 microM for Ni(II). For MutT, they were 60 +/- 6 microM for Cd(II), 102 +/- 8 microM for Cu(II), 1461 +/- 96 microM for Ni(II) and 8788 +/- 1003 microM for Co(II). Thus, Cu(II) and Cd(II) emerged as much stronger inhibitors than Ni(II) and Co(II), and MTH1 appeared to be generally more sensitive to metal inhibition than MutT. Interestingly, in the absence of Mg(II), the activity of the enzymes could be restored by Co(II) to 73% of that with Mg(II) alone for MutT, and 34% for MTH1, the other metals being much less or non-effective. The difference in sensitivity to metal inhibition between the two enzymes may reflect the differences in the amino acid ligands, especially the cysteine ligand, outside their evolutionarily conserved Mg(II)-binding active sites, which might indicate predominantly non-competitive or uncompetitive mechanism of the inhibition. The overall results suggest that inhibition of 8-oxo- dGTPases may be involved in the mechanisms of induction of the 8- oxoguanine lesion in DNA by the metal ions studied, especially the non- redox-active Cd(II) cation.      

Localized muscular mucormycosis in a child with acute leukemia

Mucormycosis is a rare fungal infection of childhood, occurring mainly in patients with chronic illnesses such as diabetes and malignancies. The fungus seldom grows in culture and confirmation of the diagnosis depends on histologic examination of infected tissues. To date, the reported natural history of the disease has been rapid progression and a fatal outcome. Therefore, the importance of early diagnosis by tissue biopsy and early treatment with surgical debridement and systemic antifungal therapy cannot be overemphasized. The pulmonary system is the most common site for mucormycosis in patients with leukemia. We report what we believe to be the first successfully treated case of isolated muscular mucormycosis occurring in a child with biphenotypic acute leukemia. The diagnosis was made promptly by tissue examination at the time of surgical debridement. The patient was also given systemic amphotericin-B therapy.