Leukocyte recruitment in hepatic injury: selectin-mediated leukocyte rolling is a prerequisite for CD18-dependent firm adhesion.

BACKGROUND/AIMS: This study was designed to examine the role of selectins and CD18 in leukocyte recruitment in hepatic injury induced by tumor necrosis factor-alpha (TNF-alpha) and galactosamine (Gal) in vivo. METHODS: Intravital fluorescence microscopy of the hepatic microcirculation was used to quantify leukocyte-endothelium interactions provoked by 24 h of systemic TNF-alpha/Gal challenge in rats. Hepatic injury was evaluated with liver enzymes. RESULTS: When administered after 24 h of TNF-alpha/Gal challenge, fucoidan, a selectin-function inhibitor, reduced leukocyte rolling by 69%, whereas firm adhesion was unaltered. In contrast, passive immunization against CD18 decreased leukocyte adhesion by 60%, whereas rolling remained unchanged. Notably, when administered prior to TNF-alpha/Gal, fucoidan attenuated both leukocyte rolling and adhesion, by 57 and 69%, respectively. Pretreatment with an anti-CD18 antibody decreased TNF-alpha/Gal-induced rolling and firm adhesion by 25 and 90%, respectively. Moreover, pretreatment with fucoidan and the anti-CD18 antibody both protected against TNF-alpha/Gal-induced increases in liver enzymes. For example, the pretreatments reduced alanine aminotransferase by 59 and 87%, respectively. CONCLUSIONS: Our data suggest that TNF-alpha/Gal-induced leukocyte rolling is selectin-mediated and a precondition for CD18-dependent firm adhesion in hepatic venules. Thus, reducing leukocyte recruitment by inhibition of selectins or CD18 may be useful to control TNF-alpha-induced liver injury.     

TβRⅡ,MMP-7,TIMP-2表达及在HNPCC侵袭转移中的作用

目的:通过观察TβRⅡ,MMP-7及TIMP-2在HNPCC和散发性大肠癌中的表达,探讨其在HNPCC侵袭转移的生物学行为中的作用.方法:选取1980-05/2005-06空军总医院收治的HNPCC和散发性大肠癌各30例,应用免疫组化SP染色法检测其肿瘤组织中TβRⅡ,MMP-7,TIMP-2的表达情况.结合其相应临床病理资料进行分析TβRⅡ,MMP-7,TIMP-2表达在HNPCC侵袭转移中的作用.结果:TβRⅡ,MMP-7,TIMP-2在HNPCC组的阳性表达率分别为4 0.0%,46.7%,63.3%;而在散发性大肠癌组的阳性表达率为73.3%,86.7%,20.0%.散发性大肠癌组中MMP-7( ～ )/TIMP-2(-)比例明显高于HNPCC组.而其MMP-7(-)/TIMP-2( ～ )者则明显少于HNPCC组.TβRⅡ,MMP-7,TIMP-2的阳性表达率与肿瘤的大小和部位无关.而与肿瘤的侵犯深度和转移与否密切相关.侵犯浆膜外组织和有转移者的MMP-7的阳性表达率明显增高,而TβRⅡ,TIMP-2的阳性表达率则明显降低(P＜0.05).在两组大肠癌中TβRⅡ与MMP-7呈正相关(r=0.735,P=0.000;r=0.792,P=0.000),TIMP-2与TβRⅡ(r=-0.582,P=0.001;r=-0.394,P=0.031)和MMP-7 (r=-0.473,P=0.008;r=-0.388,P=0.034)的表达均呈负相关.结论:TβRⅡ,MMP-7,TIMP-2在散发性大肠癌和HNPCC中的表达差异显著.TβRⅡ,MMP-7在散发性大肠癌中的表达率和表达强度明显高于HNPCC,而TIMP-2的表达结果则相反.因此,散发性大肠癌中MMP-7/TIMP-2的比例失衡明显高于HNPCC组.     

Spontaneous Rupture of the Spleen Secondary to Metastatic Hepatocellular Carcinoma: A Report of a Case and Review of the Literature

An extremely rare case of splenic rupture at the site of metastasis of hepatocellular carcinoma is reported. A 62-yr-old woman with hepatocellular carcinoma and its suspected metastasis to the spleen died of intraperitoneal hemorrhage. Autopsy disclosed a laceration of the spleen as the definitive cause of the hemorrhage. There were multiple nodules of metastatic hepatocellular carcinoma in the spleen, some of which were exposed at the lacerated portion of the splenic capsule. This may be the first report of a case of spontaneous rupture of the spleen secondary to metastatic hepatocellular carcinoma. Splenic rupture can he one of the causes of hemoperitoneum in patients with hepatocellular carcinoma.     

Progesterone and human chorionic gonadotropin do not stimulate placental proteins 12 and 14 or prolactin production by human decidual tissue in vitro

To investigate the regulation of the synthesis and secretion of placental proteins-12 (PP12) and -14 (PP14) and PRL, explants and enriched preparations of stromal cells and gland cells obtained from 10 human early pregnancy decidua were preincubated in medium for 24 h (baseline), followed by incubation in medium with or without progesterone (0.02-32 mumol/L), hCG (10 and 100 ng/ml), or cAMP (0.25-1 mmol/L) in an atmosphere of 5% CO2-95% air at 37 C for another 96-120 h. Media were changed each 24 h, and PP12, PP14, and PRL levels were determined by RIA. Decidual explants, as well as their isolated cells produced detectable levels of PP12, PP14, and PRL in vitro. The gland cells synthesized and secreted about 30 times more PP14 than did stromal cells. After 96-120 h of incubation, the production of each protein by control cultures was increased 81-167% compared to the baseline (not significant). The secretion of these proteins in medium supplemented with progesterone or hCG was not significantly different from that in the control groups. 8-Bromo-cAMP significantly increased the secretion of PRL and PP12, but not PP14, by stromal cells compared to control values. We conclude that 1) PP14 is mainly produced by decidual gland cells; 2) progesterone at the concentrations used in our study does not stimulate production of PP12, PP14, and PRL in decidualized endometrium in vitro; 3) hCG does not stimulate the production of PP12 and PP14 in decidualized endometrium; and 4) 8-bromo-cAMP stimulates decidual stromal cell secretion of PRL and PP12.     

Influence of gender and diabetes on vascular and myocardial contractile function.

Premenopausal women have a lower cardiovascular risk than men or postmenopausal women. However, this "female advantage" is lost in diabetes, a condition characterized by cardiac and vascular contractile dysfunction. This study was designed to compare the influence of diabetes on vascular and myocardial contractile function between genders. Adult male and female rats were made diabetic with streptozotocin (55 mg/kg) and maintained for 8 weeks. Tension development was examined in thoracic aortic rings and left ventricular papillary muscles. KCl-induced vasoconstriction, acetylcholine (ACh)-induced endothelium dependent or sodium nitroprusside (SNP)-induced endothelium-independent vasorelaxation, duration and maximal velocity of myocardial contraction and relaxation duration (TPT/RT90 and +/- VT) were similar between males and females. Diabetes augmented KCl-induced vasoconstriction at low doses, reduced SNP-induced vasorelaxation and had little effect on ACh-induced vasorelaxation in aortic rings from both genders. Diabetes prolonged TPT and RT90 in both genders, and reduced +/- VT in males but not females. Acute increase in extracellular Ca2+ (2.7 mM to 5.4 mM) shortened TPT in diabetic myocardium from both genders, whereas it had no effect on other myocardial mechanical indices in normal or diabetic groups of either gender. In addition, acute exposure to the Na+/K(+)-ATPase inhibitor ouabain shortened TPT/RT90 and enhanced +/- VT in myocardium from normal female, whereas it had no effect on male or diabetic myocardium. In conclusion, these data suggest that in the vasculature, there is no difference in diabetes-induced contractile dysfunction between genders, however several gender-specific differences are evident in the myocardium.     

万古霉素等十种抗生素对耐苯唑西林葡萄球菌的体外活性比较

为了比较万古霉素等１０种抗生素对１９９５年分离的９５株耐苯唑西林的金黄色葡萄球菌和７２株凝固酶阴性葡萄球菌的体外活性，用ＮＣＣＬＳ颁布的琼脂稀释法测ＭＩＣ。结果受检的１０种抗生素中万古霉素的活性最好，其ＭＩＣ５０及ＭＩＣ９０分别为１ｍｇ／Ｌ及２ｍｇ／Ｌ，平均值为１２４ｍｇ／Ｌ；耐药率为０％。其次为壁霉素，其ＭＩＣ５０及ＭＩＣ９０分别为２ｍｇ／Ｌ及８ｍｇ／Ｌ，平均值为２５１ｍｇ／Ｌ；耐药率为２％。利福平ＭＩＣ５０及ＭＩＣ９０分别为０１２５ｍｇ／Ｌ及３２ｍｇ／Ｌ，平均值为０２２ｍｇ／Ｌ；耐药率为１４％。其它依ＭＩＣ９０的大小排序，为氧氟沙星，甲氧苄啶，红霉素，庆大霉素，磷霉素，磺胺甲恶唑等。用柱状图显示了前三种药的ＭＩＣ值的分离，万古霉素具有良好的分散性，全部落在敏感区，且为单峰。结果表明万古霉素对ＭＲＳＡ和ＭＲＳＣｏＮ有良好的抗菌活性。     

Potent and nontoxic antisense oligonucleotides containing locked nucleic acids

Insufficient efficacy and/or specificity of antisense oligonucleotides limit their in vivo usefulness. We demonstrate here that a high-affinity DNA analog, locked nucleic acid (LNA), confers several desired properties to antisense agents. Unlike DNA, LNA/DNA copolymers were not degraded readily in blood serum and cell extracts. However, like DNA, the LNA/DNA copolymers were capable of activating RNase H, an important antisense mechanism of action. In contrast to phosphorothioate-containing oligonucleotides, isosequential LNA analogs did not cause detectable toxic reactions in rat brain. LNA/DNA copolymers exhibited potent antisense activity on assay systems as disparate as a G-protein-coupled receptor in living rat brain and an Escherichia coli reporter gene. LNA-containing oligonucleotides will likely be useful for many antisense applications.     

糖尿病患者心率变异性的临床观察及评价

用心率变异性（ＨＲＶ）分析技术，观察糖尿病患者ＨＲＶ时域的六项指标变化：①ａｖｇＲＲ：ＲＲ间期平均值；②ＳＤＡＮＮ：４分钟ＲＲ平均值的标准差；③ＣＶ：变异系数；④ＳＤ：每４分钟ＲＲ间期标准差的平均值；⑤ＳＤＳＤ：ＳＤ的标准差；⑥ｒｍＳＡＳＤ：每４分钟内相邻ＲＲ间期差值作均方根后的平均值。Ⅱ型糖尿病患者２５例，正常对照组１８例，两组年龄相似。结果表明，糖尿病组的ＳＤ，ＳＤＡＮＮ及ｒｍＳＡＳＤ显著低于对照组，而ａｖｇＲＲ无显著变化。为分析记录时间上的差异性，选择８１例正常人，分成上午组（４５例）与下午组（３６例），除ＳＤＡＮＮ外，其余五项指标在上午组与下午组之间无显著差别。结论认为糖尿病患者的ＨＲＶ显著减小，说明ＨＲＶ对糖尿病有一定的临床应用价值。     

每周化疗合并局部放疗治疗晚期肺癌的临床研究

目的　对比每周化疗加局部放疗与单纯化疗对晚期非小细胞肺癌的疗效。方法　对初次化疗失败的非小细胞肺癌患者行每周化疗合并局部放疗 ,对初次化疗有效的病例继续行同一方案化疗。结果　放化疗组有效率为 6 6 .6 % ,单纯化疗组有效率为 70 .2 % ,二者之间无显著性差异 (P>0 .0 5 )。二者副作用 - 级白细胞减少的发生率 ,放化疗组较单纯化疗组明显下降 (P<0 .0 5 )。结论　每周化疗结合局部放疗是改善晚期肺癌初次化疗失败的一种有效方法