Hybrid imaging with PET/MRI: ready for clinical routine?

The introduction of integrated PET/MRI imaging combining full magnetic resonance imaging and positron emission tomography is a new milestone in tissue imaging. As usual innovations in clinical practice generate new dilemmas. The questions it poses are: when to use PET/MRI scanning, what radiopharmaceutical to use and how to optimize examination protocols. A range of new radiopharmaceuticals, in addition to 18F-fluorodeoxyglucose (18F-FDG), are now available for assessing and characterizing tissues.     

HBV适应性杂交细胞株的建立和初步研究

目的方法诱导HepG₂细胞产生HGPRT基因突变,将筛选出的HGPRT阴性的HepG2细胞与携带HBV的人原代肝细胞进行融合得杂交细胞,用HAT培养基筛选出异核体杂交细胞,再利用有限稀释法进行克隆,通过核型分析方法鉴定所得细胞。对所得杂交细胞及培养上清液进行HBV DNA和HBsAg、HBeAg的检测。实验同时,用未杂交的HepG2和人原代肝细胞作对照。结果经筛选后,有一杂交细胞株(HepCHLine3)克隆成功。HepCHLine3在形态学上与HGPRT^-HepG₂细胞相似,能体外传代培养,染色体核型分析示HepCHLine3杂交细胞染色体众数为99条,证明为融合细胞株,含所有来自HepG₂和人原代肝细胞的基因数。传代培养的HepCHLine3和其培养上清液用巢式PCR分别可检测到HBV DNA,培养上清液内检测到HBsAg和HBeAg。对照组的HepG₂和人原代肝细胞相应结果为阴性。提示该细胞携带并分泌HBV DNA。结论该杂交细胞兼具HepG₂细胞体外传代和人原代肝细胞对HBV易感的特性,是一新型杂交细胞系,为进一步建立新型HBV感染细胞模型奠定了基础。     

Slight impairment of Na+,K+-ATPase synergistically aggravates ceramide- and beta-amyloid-induced apoptosis in cortical neurons

Dysfunction of the Na(+),K(+)-ATPase (Na(+),K(+)-pump), due to reduced energy supply or increased endogenous ouabain-like inhibitors, likely occurs under pathological conditions in the central nervous system. In cultured mouse cortical neurons, we examined the hypothesis that a mild non-toxic inhibition of the Na(+),K(+)-ATPase could synergistically sensitize the vulnerability of neurons to normally non-lethal apoptotic signals. Ouabain at a low concentration of 0.1 microM slightly lessened the Na(+),K(+)-pump activity measured as an ouabain-sensitive current, yet did not affect K(+) homeostasis and viability of cortical neurons. Co-exposure to 0.1 microM ouabain plus non-lethal C(2)-ceramide (5 microM) or beta-amyloid 1-42 (5 microM), however, induced marked intracellular K(+) loss, caspase-3 cleavage, DNA laddering, and synergistically triggered neuronal death. The caspase inhibitor Z-Val-Ala-Asp(OMe)-fluoromethyl ketone (Z-VAD-FMK) predominantly blocked the caspase activation and neuronal death. These results suggest that slight impairment of Na(+),K(+)-pump activity may amplify the disruption of K(+) homeostasis in the presence of a non-lethal apoptotic insult, leading to activation of apoptotic cascade and substantial neuronal injury.     

Hybrid MR interventional imaging system: combined MR and angiography suites with single interactive table. Feasibility study in vascular liver tumor procedures

Our objective was to evaluate the feasibility of a hybrid system consisting of a high-field MR and fully equipped digital subtraction angiography (DSA) unit for MR-guided vascular interventions. In a newly built hybrid system, consisting of a high-field MRI and a fully equipped DSA unit, elective interventional hybrid procedures were performed. Between May 2000 and November 2001, 30 patients with liver tumors underwent MR-guided chemoembolization using the hybrid system. During the intervention accurate catheter position was monitored with real-time and dynamic MR imaging. Elective hybrid interventional vascular procedures were performed successfully in 23 patients with liver metastases and hepatocellular carcinoma ( n=7). Patients could be transferred between the MRI and angiographic units on a carbon fiber tabletop within 10 s. Initial clinical trials demonstrated that in the chemoembolization of primary and secondary liver tumors the hybrid approach resulted in a change of catheter position in 40% of procedures. In combining high-field MR system and a fully equipped interventional vascular angiographic unit as backup, this hybrid system improves the therapeutic capabilities of interventional vascular procedures in the liver.     

累及11p15上NUP98基因的急性杂合性白血病的临床遗传学分析

目的运用细胞遗传学和分子遗传学方法，阐明1例与NUP98基因相关的急性杂合性白血病的临床遗传学特点。方法采用骨髓直接法和短期培养法制备染色体，应用R显带技术进行核型分析；采用3号和11号整条染色体涂染探针进行染色体涂染；用地高辛标记的跨越NUP98基因的BACRP11-120E20探针进行间期和中期荧光原位杂交（FISH）检测。结果R显带分析显示47，XX，t（3；11）（q13；p15），＋21；染色体涂抹证实3号和11号染色体之间发生了相互易位；间期和中期FISH均显示该染色体异常累及NUP98基因。结论识别一种累及NUP98基因的新的染色体易位，为下一步研究NUP98基因新的对手基因及其在白血病发病中的作用机制打下基础。     

基于分形和小波的混合图像压缩

从近年来受人瞩目的分形和小波图像压缩方法出发,分析了两种图像压缩方法的特点及利弊。运用小波域及DCT域下的分形压缩图像方法,提高了编码速度,得到较高的压缩比和信噪比,但重构图像质量还存在块状效应。为此,提出了几种方法结合起来的综合方法,进一步提高图像的质量,在压缩比和信噪比之间取得良好的折衷。     

Alcohol impairs protein synthesis and degradation in cultured skeletal muscle cells

BACKGROUND: Acute and chronic alcohol intoxication decreases skeletal muscle protein synthesis under in vivo conditions. We investigated whether ethanol (EtOH) and its major metabolites, acetaldehyde and acetate, can directly modulate protein balance under in vitro conditions. METHODS: Human myocytes were incubated with different doses of EtOH for varying periods of time (i.e., 4-72 hr). Alternatively, cells were incubated with acetaldehyde, acetate, insulin, insulin-like growth factor-I (IGF-I), or with a combination of EtOH plus insulin or IGF-I. Rates of protein synthesis or degradation were determined by 35S-methionine/cysteine incorporation into or release from cellular protein. RESULTS: A significant, 15% to 20%, decrease in basal protein synthesis was observed after 24 hr, but not at earlier time points, in response to 80 mM EtOH. Incubation of myocytes for 72 hr decreased synthesis in cells incubated with EtOH ranging between 60 and 120 mM. The ability of IGF-I or insulin to stimulate protein synthesis was impaired by 30% and 60%, respectively, in cells incubated with 80 mM EtOH for 72 hr. Exposure of cells to 200 microM acetaldehyde or 5 mM Na-acetate also decreased basal protein synthesis. In contrast, neither EtOH, acetaldehyde, nor acetate altered the basal rate of protein degradation. However, EtOH completely impaired the ability of insulin and IGF-I to inhibit proteolysis. Finally, EtOH did not impair IGF-I receptor autophosphorylation, but inhibited the ability of insulin to phosphorylate its own receptor. EtOH also did not alter the number of insulin or IGF-I receptors or the formation of insulin/IGF-I hybrid receptors. CONCLUSIONS: We have demonstrated that EtOH can directly inhibit muscle protein synthesis under in vitro conditions. Neither EtOH nor its metabolites altered basal protein degradation, although EtOH did compromise the ability of both insulin and IGF-I to slow proteolysis. This impairment seems to be mediated by different defects in signal transduction.     

Therapeutic Effect of Ansamitocin Targeted to Tumor by a Bispecific Monoclonal Antibody

We have constructed a murine hybrid hybridoma that secretes a bispecific monoclonal antibody (mAb) by fusing a hybridoma secreting an anti-ansamitocins mAb with a hybridoma secreting an anti-human transferrin receptor (TfR) mAb that binds to human A431 epidermoid carcinoma cells. The bispecific mAb, reactive to both ansamitocins and TfR, was purified by a combination of hydrophobic column chromatography and hydroxyapatite high-performance liquid chromatography, and evaluated in in vivo experiments using human tumor cell-implanted nude mice. Ansamitocin P-3 targeted through one of the antigen combining sites of the bispecific mAb was potentially more effective in suppressing the growth of established A431 tumor xenografts implanted on nude mice than unconjugated ansamitocin P-3 or the immunoconjugate of ansamitocin P-3 and monospecific anti-ansamitocins antibody, and the targeted ansamitocin P-3 finally eradicated the tumor mass. The bispecific mAb also played an important role in reducing such undesirable side-effects of ansamitocin P-3 as the loss of body weight, the damage to liver functions and the decrease in the number of white blood cells.     

A volume-sensitive Cl conductance in a mouse neuroblastoma × rat dorsal root ganglion cell line (F11)

Whole cell currents were recorded in F11 cells, a mouse neuroblastoma (NG18TG2) × rat DRG hybrid cell line, using pipette and bath solutions intended to isolate any chloride conductance pathways. When recording with a pipette solution which was 40 mmol·kg⁻¹ hypotonic to the bath solution, all cells showed a transient rise in input conductance which peaked 5.3±0.4 min after breaking into the cell and returned to the basal state 11.7±1.2 min later. At the peak of the effect, cell conductance had increased approximately sixfold. The use of short (300 ms) duration voltage steps at the peak of the conductance increase evoked whole-cell currents which were time-independent and had an outwardly rectifying current/voltage relationship. Ion substitution experiments showed that the whole-cell currents were carried by chloride ions and that the anion selectivity sequence of the conductance was I > Br > Cl > F > acetate. The stilbene derivative 4,4′-diisothiocyanostilbene-2,2′-disulphonic acid (DIDS) caused a reversible, 51% inhibition of the chloride currents. In cells which had already undergone this transient rise in conductance, whole-cell currents with identical properties could be activated by changing to a very hypotonic bath solution. Coincident with current activation, this manoeuvre caused a visible swelling of the cell. The increase in conductance and the cell swelling were both reversed by returning to the normal bath solution. In contrast, when a very hypotonic pipette solution was used, little or no increase in cell conductance was observed. These data suggest that the F11 cell line possesses a volume-activated chloride conductance which can be controlled by manipulating the relative osmolarity of the bath and pipette solutions.