用99Tcm-HL91评价鼠心肌缺血模型

目的 探讨乏氧心肌显像剂99Tcm-4,9-二氮-3,3,10,10-四甲基十二烷-2,11-二酮肟(HL91)用于诊断实验性缺血心肌的价值.方法 建立大鼠心肌在体缺血再灌注模型,采用体外放射自显影法检测正常对照组(6只)、缺血再灌注组(8只)及无再灌注组(8只)鼠心肌对99Tcm-HL91的摄取.结果 对照组和无再灌注组心肌未见局灶性放射性浓聚,再灌注组心肌非坏死区有较高放射性浓聚,与正常心肌组织的摄取比值为1.634±0.354.结论 99Tcm-HL91表现出较强的亲乏氧组织特性,能较好区分存活和梗死心肌.     

99Tcm-HL91乏氧显像在甲状腺结节良恶性鉴别诊断中的应用

目的 评价99Tcm4,9-二氮-3,3,10,10-四甲基十二烷-2,11-二酮肟(HL91)对甲状腺结节良恶性鉴别诊断的临床价值.方法 对58例经触诊或超声检查存在甲状腺结节的患者进行99Tcm-HL91甲状腺早期(10 min)及延迟(4 h)平面显像,应用感兴趣区(ROI)技术计算靶/非靶(T/N)比值并进行比较.组间比较采用成组设计两样本均数t检验,率的比较用χ2检验.结果 患者均经手术或细针穿刺病理检查,其中21例为甲状腺癌,37例为甲状腺良性结节.99Tcm-HL91显像诊断甲状腺癌的灵敏度、特异性和准确性分别为85.7%,94.6%和91.4%,不同甲状腺癌病理类型的显像灵敏度差异无统计学意义(χ2=0.778,P＞0.05),但结节越大灵敏度越高.甲状腺癌与甲状腺良性结节组早期及延迟相T/N比值分别为1.07±0.04,1.25±0.03和0.92±0.10,0.91±0.12,组间在10 min时T/N比值差异无统计学意义(t=1.900,P＞0.05),4 h时T/N比值差异有统计学意义(t=3.885,P＜0.001).结论 用99Tcm-HL91乏氧显像判断甲状腺结节的良恶性有一定的临床价值,显像时间以4 h为佳.     

用ROC曲线法分析99Tcm-HL91肺肿瘤阳性显像的诊断效能

目的探讨半定量分析及接受器工作特性(ROC)曲线法在99Tcm-4,9-二氮-3,3,10,10-四甲基十二烷-2,11-二酮肟(HL91)肿瘤阳性显像鉴别肺部良恶性肿块中的价值.方法经CT检查发现肺部肿块的患者50例,均经活组织检查或手术病理检查证实.根据病理检查结果分为恶性组37例和良性组13例.术前行99Tcm-HL91 2 h、4 h平面显像及4 h断层显像,分别使用视觉判断法、半定量分析及ROC曲线法分析显像结果.结果①视觉判断法99Tcm-HL91显像的灵敏度、特异性和准确性分别为97.3%、69.2%和90.0%.②肿瘤/正常肺组织(T/N)比值半定量分析及ROC曲线法恶性组2 h、4 h平面显像及4 h断层显像T/N比值分别为1.52±0.19、1.73±0.28及2.84±0.97;良性组分别为1.20±0.16、1.24±0.20及1.52±0.40.各个时相的曲线下面积分别为0.909±0.056、0.945±0.039、0.953±0.034.从99Tcm-HL91断层显像ROC曲线的界值点找到1个界点(T/N=1.76),以其作为判断良、恶性的诊断阈值,灵敏度、特异性和准确性分别为100%、84.6%和96.0%.③视觉判断法与半定量分析法比较T/N比值半定量分析及ROC曲线法使诊断的灵敏度、特异性和准确性都有提高,尤其特异性.但两种方法间差异无显著性(P均＞0.05).结论半定量分析及ROC曲线法的诊断阈值可进一步提高99Tcm-HL91肺部肿瘤阳性显像的诊断效能.     

The common heat shock protein receptor CD91 is up-regulated on monocytes of advanced melanoma slow progressors

Despite advances in our understanding of tumour immunology there is no therapy of proven survival benefit for advanced melanoma. Nevertheless, disease progression is slow in a small proportion of patients with metastatic melanoma, suggesting a contribution to outcome from host factors. Recent data have indicated the importance of the heat shock protein receptor CD91 in immune responses to, and progression of, infectious disease. Here we investigate the relationship between CD91 expression and outcome in malignancy. Rare melanoma patients were recruited with advanced disease that was progressing unusually slowly. CD91 expression on their monocytes was compared with control patients with more typical rapidly advancing metastatic disease. Th1 and Th2 cytokines, as well as innate and adaptive immune subsets, were also measured in the two groups. A significant increase in median CD91 expression levels was observed in slow progressors (P = 0.006). There were no differences in other immune subset markers or inflammatory cytokines. The ability of CD91 to internalize and cross-present tumour antigens through the major histocompatibility complex class I pathway may maintain CD8-positive cytotoxic T cell responses and contribute to slow progression of advanced melanoma.     

Intimal changes associated with arterial spasm induced by periarterial application of calcium chloride

Arterial spasm was induced by application of calcium chloride to the adventitial surface of the rabbit common carotid artery in vivo. Sodium chloride (NaCl) was applied to the contralateral vessel as control. Vessels were fixed in situ by intravascular perfusion after 15 min, 1 hr, or 24 hr and prepared for light and scanning electron microscopy (SEM). With SEM, the luminal surface at the site of calcium application showed severe longitudinal folding accompanied by endothelial desquamation with extensive platelet deposition on exposed subendothelium. The luminal cross-sectional area was reduced by 53 +/- 19.5% after 15 min and by 44 +/- 12% after 1 hr as compared with the contralateral control. Furthermore, the luminal area at the site of calcium application was found to be reduced by 42 +/- 8% after 1 hr when compared with segments of the same vessel distal to the site of calcium application. Blood flow rate, as measured by electromagnetic flow probe, was not reduced. Vessels examined after 24 hr showed a significant increase in luminal cross-sectional area as compared with contralateral control vessels (136 +/- 70%). Control vessels (NaCl) showed no significant change in luminal cross-sectional area and no endothelial desquamation or platelet deposition after 15 min, 1 hr, or 24 hr. Examination of histologic sections showed calcium precipitation within the attached thrombus after 15 min with calcium deposits also adherent to the adjacent luminal aspect of the internal elastic lamina (IEL). By 24 hr, this precipitation extended throughout the media. Marked deposition of leukocytes was seen after 24 hr which showed a preferential attachment for areas of endothelial damage and discontinuity of IEL.     

IFN-γ在沙眼衣原体呼吸道感染中免疫防御机制的探讨

目的:检测与IFN-γ作用相关的酶吲哚胺2,3二氧化酶(IDO)、诱导性一氧化氮合成酶(iNOS)和NADPH氧化酶(ox)gp91在沙眼衣原体呼吸道感染中的表达及与机体防御的关系,探讨衣原体感染中IFN-γ免疫防御作用的机制.方法:用沙眼衣原体小鼠肺炎株(MoPn)通过鼻腔感染C57BL/6(H-2b)小鼠,用过氧化物酶连接的鼠抗衣原体脂多糖单抗染色HeLa 229细胞,检测衣原体在肺组织的生长;用RT-PCR检测衣原体感染后第7及14天小鼠肺组织IFN-γ、IDO、iNOS和gp91NADPH ox mRNA表达.结果:MoPn呼吸道感染后小鼠肺组织匀浆衣原体活性测定,于感染后第2天,HeLa 229细胞内可见有衣原体包涵体生长,IFU值增高,于感染后第7天IFU达最高水平,以后逐渐下降,至感染后21天基本恢复到基线水平.与未感染的对照组比较,Th1细胞因子IFN-γ于感染后第7天表达显著增高,感染后14天有所降低,但仍维持较高水平;同时衣原体感染可显著诱导与IFN-γ作用相关的三种酶IDO、iNOS和gp91 NADPH ox在小鼠肺组织的表达,感染后第7及14天,IDO,iNOS及gp91 NADPH ox的表达与对照组比较均有显著差异,其中IDO和gp91 NADPH ox于感染后第7天mRNA表达增高显著(P＜0.01),14天略有下降(P＜0.05).结论:衣原体呼吸道感染诱导Th1细胞因子IFN-γ mRNA高表达,参与宿主对衣原体的清除及机体免疫防御,此作用可能与其相应的酶IDO、iNOS和gp91 NADPH ox表达增高有关.     

Discriminative stimulus properties of β-carbolines characterized as agonists and inverse agonists at central benzodiazepine receptors

The discriminative stimulus properties of three -carboline derivatives were studied in three groups of rats trained, respectively, to discriminate diazepam (2.5 mg/kg IP), chlordiazepoxide (CDP, 5 mg/kg IP) or pentylenetetrazol (PTZ, 15 mg/kg IP) from saline in standard procedures employing two-lever operant chambers. Two -carbolines, ZK 91296 and ZK 93423, substituted for the benzodiazepines in both CDP- and diazepam-trained rats. The neutral benzodiazepine antagonist Ro 15-1788 blocked the diazepam discriminative stimulus and the ability of ZK 91296 to substitute for diazepam. A third -carboline, FG 7142, was not identified as benzodiazepine-like in generalization tests in either diazepam- or CDP-trained rats, but when administered together with CDP antagonized the benzodiazepine discriminative stimulus. In rats trained to discriminate PTZ from saline (a discrimination which is thought to depend on the anxiogenic properties of PTZ) the PTZ cue was antagonized by diazepam and ZK 93423, and partially antagonized by ZK 91296. The PTZ cue generalized to FG 7142 and this generalization was partially antagonized by Ro 15-1788. These results suggest that the three -carbolines provide more than one kind of discriminative stimulus, consistent with the classification of ZK 93423 as an agonist at central benzodiazepine receptors, with ZK 91 296 as a partial agonist, and with FG 7142 as an inverse agonist. Pharmacologically, ZK 93 423 and ZK 91 296 may exhibit anxiolytic qualities, whereas FG 7142 produces anxiogenic effects.     

99m Tc-HL91 "hot spot" imaging of mice bearing human carcinoma by gamma camera and the effects of tumor necrosis on imaging

Objective To evaluate the hypoxia-avid agent ^99m Tc-HL91 (^99m Tc labeled 4, 9-diaza-3, 3, 10, 10-tetramethyldodecan-2, 11-dione dioxime) as the tracer of tumor "hot spot" imaging and the influence of tumor necrosis on the image.
Methods After injection of ^99m Tc-HL91, 6 nude mice bearing human breast cancer MCF-7 and 18 nude mice bearing human pancreatic adenocarcinoma were subjected to gamma camera imaging, postmortem analysis, and autoradiography and imaging of tumor sections.
Results The image of tumor was identified 1 hour after injection of ^99m Tc-HL91.Images demonstrated gradually increased ^99m Tc-HL91 uptake in the tumor 1-12 hours after injection (P<0.05-0.001).Six hours after injection, the radioactivity ratios of tumor to thorax and tumor to head were higher than 2.1.Six hours after injection, the radioactivity ratios of tumor to brain, muscle, blood, heart, lung and kidney in pancreatic adenocarcinoma bearing nude mice were 101.0±114.7, 30.0±30.3, 19.9±21.9, 14.4±15.1, 3.71±2.41 and 0.46±0.26, respectively, and the radioactivity ratios in breast cancer MCF-7 bearing nude mice were close to these figures.The radioactivity of non-necrotic tumor was 3.77 times that of necrotic tumor.However, the radioactivity ratios of tumor to liver, intestine and stomach were lower than 1.3. Autoradiographs and images of tumor sections showed that the radioactivity was higher in the region of solid tumor than in the necrotic region.
Conclusion ^99m Tc-HL91 via gamma camera positively identifies regional tumor in nude mice bearing human cancer.^99m Tc-HL91 retention is lower in necrotic tumor than in non-necrotic tumor.The low radioactivity ratio of tumor to abdominal organs limits the application of ^99m Tc-HL 91 in detecting abdominal tumors.      

99Tcm-HL91 SPECT/CT显像检测高血压脑出血乏氧组织的初步观察

目的探讨乏氧组织显像剂99Tcm-4,9-二氮-2,3,10,10-四甲基十二烷-2,11-二酮肟(HL91)SPECT/CT脑显像检测高血压脑出血出血灶周围乏氧组织的应用价值。方法22例高血压脑出血患者,和6例正常人均进行99Tcm-HL91SPECT脑显像,所有研究对象同时进行同机CT扫描。结果22例患者中18例阳性,阳性率为77.78%。4例阴性者分别是3例出血量<15ml的小量脑出血和1例出血量为23.5ml,起病43d行乏氧检查者。对照组6例均为阴性。乏氧区位于出血区周围,少量出现在血肿内,乏氧体积大小与出血量有正相关关系。结论99Tcm-HL91SPECT显像可较好地显示高血压脑出血病病灶周围的乏氧组织,乏氧体积与出血量有密切关系,可应用于指导临床治疗。     

99mTc-HL91和Tl-201双核素心肌显像在冠心病中的初步临床研究

目的 探索^99mTc-HL9乏氧心肌显像在冠心病中的可行性及临床应用价值。方法3例急性心肌梗塞,1例不稳定性心绞痛连续病例行Tl-201和^99mTc-HL9双核素心肌显像，比较两种核素心肌显像、阳性节段数以及匹配方式。结果 ^99mTc-HL9可以提供较清晰的乏氧心肌图像并用于心肌节段分析；3例急性心肌梗塞，1例不稳定性心绞痛患共68个节段。Tl-201判断为阳性节段23个，占34％；^99mTc-HL9判断为阳性节段36个，占53％；24小时Tl-201延迟显像显示为可逆性分布7个节段，^99mTc-HL91均呈阳性显像；^99mTc-HL9比Tl-201多判断出13个阳性节段，占19％。双核素心肌显像有4种匹配方式：Tl-201正常^99mTc-HL9无显像，25个节段；Tl-201正常^99mTc-HL9显像。20个节段；Tl-201异常^99mTc-HL9显像，16个节段；Tl-201异常／99mTc-HL91无显像，7个节段。即刻Tl-201显像示23个异常节段。其中16个节段呈^99mTc-HL9阳性显像，占70％，24小时Tl-201延迟显像显示有7个(部分)可逆性节段。占30％，^99mTc-HL9检测缺血，存活心肌的能力显高于Tl-201(P=0．008)。结论^99mTc-HL9可以用于冠心病的心肌乏氧成像并用于心肌节段分析．乏氧显像为研究冠心病提供了新的手段。尚需大样本的临床研究。