PGA指数和透明质酸在诊断慢性乙肝肝纤维化中的价值

目的：寻找一种简便实用的诊断慢性乙型肝炎纤维化的方法。方法：以78例经肝穿刺病理证实的慢性乙型肝炎为对象，测定并比较了由PT、GGT、ApoA1组成的PGA指数和HA、LN、PⅢP、C－IV与肝内纤维化程度(S)和炎症活动度（G）的关系。结果：（1）LN、PⅢP、C－IV在轻度慢性乙肝时无明显升高，在中度慢性乙肝时明显高于正常，但与轻度慢性乙肝无差异，而PGA指数和HA不仅在轻度慢性乙肝时显著升高，而且在轻中度间差异明显.因重度慢性乙肝和活动性肝硬化时，五项指标均显著增高。（2）在G2－4期，HA、LN、PⅢP、C－IV均明显高升，但在G1期，只有PGA指数高于正常，且各期间差异显著。（3）在S1－2期，只有PGA指数、HA、C－IV明显上升，但C－IV的上升幅度远低于PGA指数和HA。（4）加以PGA＞4．5或HA＞200μg／L作为判断临界值，则两者判断肝纤维化的敏感性均＞94％，精确性＞91％，特异性＞86％，如两者结合，则分别达到98．3％、95．2％和96．4％。结论：PGA指数和HA均是反映慢性乙型肝炎患者肝内纤维化程度的良好指标，两者联合检测则可达到最大的价值效益比。     

Intracellular Ca2+ suppressed a transient potassium current in hippocampal neurons

The effects of intracellular Ca2+ (Ca2+i) on K+ currents in hippocampal cells were examined using acutely isolated cells obtained from adult guinea pigs. Whole-cell voltage-clamp recordings were carried out in a configuration that allowed a continuous perfusion of the intracellular medium. Recording media were made to block inward currents and allowed selective activation of K(+)-dependent outward currents. Voltage-dependent outward currents consisted of an initial rapidly decaying component followed by a sustained component. The time constant of decay of the transient current was about 25 msec, and previous studies (Numann et al., 1987) showed that the kinetic and pharmacological properties of this current closely resembled the A current recorded in invertebrate neurons (Connor and Stevens, 1971; Thompson, 1982). Intracellular perfusion of hippocampal cells with a solution containing elevated Ca2+ (about 4.5 x 10(-4) M) elicited outward currents at the holding potential (-45 to -55 mV) and produced changes in voltage-dependent K+ currents. The transient outward current (IA) activated by depolarization was suppressed with increases in Ca2+i. Delayed, sustained K+ currents were greatly potentiated. Data also showed that, among the 3 effects elicited by Ca2+i, suppression of IA was most sensitive to Ca2+i elevation. Previous results (Numann et al., 1987) showed that IA had a lower threshold (about -45 mV) than sustained currents (about -40 mV). By using low levels of depolarization (-40 mV), IA can be selectively activated, and the suppressive effect of Ca2+i on IA was confirmed on the kinetically isolated IA.(ABSTRACT TRUNCATED AT 250 WORDS)     

异丙酚静脉全麻复合硬膜外腔阻滞麻醉期间CO2气腹对血流动力学和氧耗的影响

OBJECTIVE: To investigate the effects of intraperitoneal CO2 insufflation on the hemodynamics, oxygen consumption (VO2) and carbon dioxide production (VCO2) during intravenous anesthesia with propofol in combination with epidural block. METHODS: Intratracheal intubation was performed after rapid induction of anesthesia and mechanical ventilation was given. Maintenance of anesthesia was achieved using continuous intravenous propofol infusion (2 mg/kg/h) ?N2O inhalation and intermittent epidural administration. Indices of hemodynamics and respiratory function were collected 5 min before induction, 1 min before CO2 insufflation, and 5, 10, 20, 30, 40, 50, 60 min after the start of insufflation and 5 min after the termination of insufflation. RESULTS: The mean arterial pressure (MAP), heart rate (HR), end-tidal PCO2 (P(ET)CO2), VO2 and VCO2 1 min before insufflation were markedly reduced(P<0.01), compared with those recorded before induction. MAP and HR did not undergo any conspicuous changes during CO2 insufflation and 5 min after insufflation termination. Compared with that 1 min before insufflation, PETCO2 was significantly increased 20 min after the start of insufflation (P<0.01), and subsequently carried on the increase though of a lesser scale. VO2 and VCO2 gradually rose after the start of insufflation, and VO2 presented a significantly elevation (P<0.01) 10 min after the insufflation while VCO2 did not show this marked increase(P<0.05) till 20 min after the insufflation in comparison with the levels before insufflation. Subsequently, VO2 continued to rise and VCO2 also retained the increase but of smaller magnitude. CONCLUSION: Intravenous propofol anesthesia combined with epidural block assisted by well-managed excessive ventilation before insufflation can alleviate the adverse effects of CO2 insufflation on respiratory and circulatory systems.     

Gene expression patterns and profile changes pre- and post-erlotinib treatment in patients with metastatic breast cancer.

PURPOSE: To delineate gene expression patterns and profile changes in metastatic tumor biopsies at baseline and 1 month after treatment with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib in patients with metastatic breast cancer. EXPERIMENTAL DESIGN: Patients were treated with 150 mg of oral erlotinib daily. Gene expression profiles were measured with Affymetrix U133A GeneChip and immunohistochemistry was used to validate microarray findings. RESULTS: Estrogen receptor (ER) status by immunohistochemistry is nearly coincided with the two major expression clusters determined by expression of genes using unsupervised hierarchical clustering analysis. One of 10 patients had an EGFR-positive tumor detected by both microarray and immunohistochemistry. In this tumor, tissue inhibitor of metalloproteinases-3 and collagen type 1 alpha 2, which are the EGF-down-regulated growth repressors, were significantly increased by erlotinib. Gene changes in EGFR-negative tumors are those of G-protein-linked and cell surface receptor-linked signaling. Gene ontology comparison analysis pretreatment and posttreatment in EGFR-negative tumors revealed biological process categories that have more genes differentially expressed than expected by chance. Among 495 gene ontology categories, the significant differed gene ontology groups include G-protein-coupled receptor protein signaling (34 genes, P = 0.002) and cell surface receptor-linked signal transduction (74 genes, P = 0.007). CONCLUSIONS: ER status reflects the major difference in gene expression pattern in metastatic breast cancer. Erlotinib had effects on genes of EGFR signaling pathway in the EGFR-positive tumor and on gene ontology biological process categories or genes that have function in signal transduction in EGFR-negative tumors.     

Persistent reversal of diabetes by transplantation of fetal pig proislets into nude mice

Facing the limited availability of human adult and fetal pancreases, fetal pig proislets (pancreatic islet precursors) were investigated in view of several inherent advantages. Six litters of fetuses of mean +/- SE gestational age 75 +/- 3 days were obtained from commercially available farm pigs. Pancreatic tissue was gently digested with collagenase, then a 10-day culture was performed. During culture, fetal proislets showed no insulin response to glucose alone but a significant response to glucose plus theophylline. The insulin content per microgram of DNA in the cultured proislets continuously increased. Histological examination by immunoperoxidase staining showed that, apart from single insulin- and glucagon-positive cells, there were no discrete islets in the pancreatic tissue and the cultured proislets. Diabetes was induced with streptozocin (STZ) in eight nude mice 3-4 wk after proislet transplantation and in another eight nude mice without transplantation. During the initial week, blood glucose levels of mice in both groups increased rapidly. The mean +/- SE peak value of blood glucose levels in the transplanted group was 20.4 +/- 2.0 mM and was 20.1 +/- 1.3 mM in the group without transplantation. Simultaneously, body weight decreased from 29.5 +/- 0.7 to 21.5 +/- 0.9 g and from 27.9 +/- 0.7 to 19 +/- 1 g in the groups, respectively. Afterward, blood glucose levels of mice in the transplanted group gradually decreased, and normoglycemia was achieved in all mice within 50 +/- 13 days after injection of STZ, i.e., 74 +/- 13 days after transplantation. The group without transplantation persistently maintained blood glucose levels greater than 16.7 mM.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential changes of retina dopamine binding sites and adenylyl cyclase responses following 6-hydroxydopamine treatment.

Both dopamine D1 and D2 receptors are present in rat retina. D1 receptors are positively coupled to adenylyl cyclase, while D2 receptors are negatively coupled. After intraocular administration of the neurotoxin 6-hydroxydopamine (6-OHDA) there is depletion of retinal dopamine by about 90%, as well as a decrease of the number of D1 and D2 receptor binding sites. Following the 6-OHDA lesion, there is an enhancement of the D1 receptor-stimulated accumulation of cyclic-AMP and a loss of D2 receptor-inhibited accumulation of cyclic-AMP. Our results suggest that some of the retinal D2 receptors are coupled to adenylyl cyclase and some are not.     

c-myc is required for osteoclast differentiation.

The role of the receptor activator of nuclear factor kappaB (NF-kappaB) ligand (RANKL)-a tumor necrosis factor (TNF)-related cytokine-in osteoclast formation has been established clearly. However, the downstream signaling pathways activated by this cytokine remain largely unknown. To identify genes that play a role in osteoclastogenesis, we used RAW 264.7 mouse monocytes as a model system for the differentiation of multinucleated osteoclasts from mononucleated precursors. RAW 264.7 cells were induced with RANKL to form multinucleated giant osteoclast-like cells (OCLs) that expressed a number of osteoclast-specific markers and were able to form resorption pits on both calcium phosphate films and bone slices. This system was used to identify genes that are regulated by RANKL and may play a role in osteoclast differentiation. The proto-oncogene c-myc was strongly up-regulated in RANKL-induced OCLs but was absent in undifferentiated cells. Expression of Myc partners Max and Mad, on the other hand, was constant during OCL differentiation. We expressed a dominant negative Myc in RAW 264.7 cells and were able to block RANKL-induced OCL formation. Northern Blot analysis revealed a delay and a significant reduction in the level of messenger RNA (mRNA) for tartrate-resistant acid phosphatase (TRAP) and cathepsin K. We conclude that c-myc is a downstream target of RANKL and its expression is required for RANKL-induced osteoclastogenesis.     

成人成骨细胞与珊瑚羟基磷灰石的体外生物相容性

目的：研究成人骨髓成骨细胞与珊瑚羟基磷灰石（carolline hydroxyapatite,CHA)在体外培养条件下的生物相容性。方法：抽取健康成人骨髓组织，置于含体积分数为10％胎牛血清的DMEM培养基中培养，传代后改用含地塞米松、β-甘油磷酸钠和维生素C的条件培养基培养，分为CHA复合细胞组和单纯细胞组，不同时间用倒置相关显微镜，HE染色光镜及扫描电镜观察，MTT法进行细胞增殖测定，并进行细胞微量蛋白含量和碱性磷酸酶的定量检测，结果：成人骨髓成骨细胞体外培养时复合或不复合CHA均生长良好，表现出典型成骨细胞的形态特征和生物学特性，CHA利于细胞的贴附，生长与增殖，并对细胞的功能无不良影响，结论：CHA是较理想的骨组织工程支架材料，成骨细胞复合CHA用于骨缺损的修复，具有广阔的临床应用前景。