胆汁刀豆球蛋白A（ConA）结合蛋白在胆固醇性结石早期形成阶段…

为了解胆固醇结石患者汁ＣｏｎＡ结合蛋白量与质的异常，应用产要和层析等方法和胆固醇结石、色素性结石及胆囊胆固醇息肉等患者的胆汁ＣＰｓ进行了定量，并对不同个体的ＣＰｓ与模拟胆汁泡相结合量及成核影响进行了比较。     

发热对豚鼠胆汁成分的影响

目的研究发热对豚鼠胆汁成分及胆石形成的影响．方法将豚鼠６０只分为致石饲料组和普通饲料组，再将每组分为发热组和对照组．皮下注射煮沸脱脂牛奶１ｍｇ／ｋｇ使发热组动物发热，每周１次，共４次．４５ｄ后将６０只豚鼠全部处死，其中发热组在处死前３６ｈ皮下注射松节油１ｍｌ／ｋｇ，使其在处死前处于发热状态．检查胆囊并取胆汁进行分析．结果致石饲料发热组结石发生率最高，为４００％，而致石饲料不发热组为１３３％（Ｐ＜００１）．发热组胆汁总蛋白（２５ｇ／Ｌ±１９ｇ／Ｌｖｓ１０ｇ／Ｌ±０９ｇ／Ｌ，Ａ２ｖｓＡ１）及胆红素浓度（７４３μｍｏｌ／Ｌ±６２６μｍｏｌ／Ｌｖｓ１２３μｍｏｌ／Ｌ±５５μｍｏｌ／Ｌ，Ｐ＜００５）较对照组明显升高．结论发热对豚鼠胆汁成分的影响在胆石形成中具有重要作用．     

急性白血病患者血浆可溶性Fas受体的水平及其意义

目的：了解急性白血病患者血浆可溶性Ｆａｓ（ｓＦａｓ）受体水平及其意义。方法：用酶联免疫吸附试验法（ＥＬＩＳＡ）检测３０例急性白血病患者的血浆ｓＦａｓ含量,并与正常对照组比较。结果：难治复发患者ｓＦａｓ含量（ＡＮＬＬ９．６９±３．５１μｇ／Ｌ; ｎ＝８,ＡＬＬ７．１４±２．１８μｇ／Ｌ; ｎ＝７）显著高于（ Ｐ＜０．０１）正常对照（３．４９±２．３６μｇ／Ｌ）和ＣＲ组（ＡＮＬＬ４．２３±１． ９８μｇ／Ｌ;ｎ＝８,ＡＬＬ ３．７２±０．７２μｇ／Ｌ; ｎ＝７）。 ＡＮＬＬ与 ＡＬＬ患者 ｓＦａｓ水平比较,差异无显著性（ Ｐ ＞０． ０５）。结论：初步提示血浆ｓＦａｓ水平升高与急性白血病预后不良有关。     

周围血单个核细胞抑制胰岛素释放的实验研究

将新发病的ＩＤＤＭ病人周围血单个核细胞（ＰＢＭＣ）同大鼠胰岛共同培养２０个小时后用Ｌ－精氨酸刺激，收集并测定基础和刺激后培养上清中胰岛素的含量，结果显示：ＩＤＤＭ病人ＰＢＭＣ作用下的基础胰岛素释放（１１７．９±１４．０±μＵ·１０ｉｓｌｅｔｓ－１／２０ｈ）（ｎ＝１１）和刺激后胰岛素释放（１４７．５±３２．３μＵ·１０ｉｓｌｅｔｓ－１／３ｈ）（ｎ＝１１），显著低于正常人ＰＢＭＣ作用下的基础胰岛素释放（１８４．８±２９．５μＵ）（ｎ＝１０，Ｐ＜０．０１）和刺激后胰岛素释放（１９５．０±２７．４μＵ）（ｎ＝１０，Ｐ＜０．０１）。结果表明新发病的ＩＤＤＭ病人ＰＢＭＣ能够抑制大鼠胰岛基础和刺激后胰岛素的释放。     

广东地区健康人群和哮喘患者外周血嗜酸细胞阳离子蛋白水平的研究

用ＰａｒｍａｃｉａＣＡＰ方法测定了２５９例健康人和１０３例慢性哮喘活动的患者血清嗜酸细胞阳离子蛋白（ＥＣＰ）水平，并分析其与痰嗜酸细胞计数、血清特异性ＩｇＥ之间的关系。结果显示：①正常个体血清ＥＣＰ水平的几何均数是４．７１μｇ／Ｌ，９５％的百分位数是１２．２０μｇ／Ｌ。血清ＥＣＰ水平高于１３μｇ／Ｌ时提示嗜酸细胞活化。②活动性哮喘患者血清ＥＣＰ水平（８．７０±１３．４０）μｇ／Ｌ显著高于健康对照组（５．４１±２．３０）μｇ／Ｌ，（Ｐ＜０．０１），但其中７５％的患者血清ＥＣＰ值＜１３μｇ／Ｌ。哮喘患者血清ＥＣＰ与血清特异性ＩｇＥ（Ｐ＜０．０１）、痰嗜酸细胞计数（ｒ＝０．５１，Ｐ＜０．０５）之间有一定正相关。     

血清层粘蛋白和Ⅳ型胶原鉴别良恶性肝肿瘤的价值

目的研究血清层粘蛋白（ＬＮ）和Ⅳ型胶原（ＣⅣ）在良恶性肝肿瘤鉴别中的价值．方法肝恶性肿瘤患者４６例，良性肝占位患者３１例，其他恶性肿瘤患者３８例和健康献血员４０例．采用放射免疫法分别测定空腹血清ＬＮ和ＣⅣ．用ＳＮ６９５型智能放射测量仪进行测量．结果肝恶性肿瘤组血清ＬＮ水平（２４７μｇ／Ｌ±９２μｇ／Ｌ）显著高于正常对照组（９５μｇ／Ｌ±２１μｇ／Ｌ，Ｐ＜００１）与良性肝肿瘤组（１０６μｇ／Ｌ±５１μｇ／Ｌ，Ｐ＜００１）；肝恶性肿瘤组血清ＣⅣ水平（４１２μｇ／Ｌ±６４μｇ／Ｌ）显著高于良性肝占位组（９０μｇ／Ｌ±２０μｇ／Ｌ，Ｐ＜００１）、其他恶性肿瘤组（９９μｇ／Ｌ±３７μｇ／Ｌ，Ｐ＜００１）和正常对照组（８４μｇ／Ｌ±１７μｇ／Ｌ，Ｐ＜００１）．血清ＬＮ和ＣⅣ对良恶性肝肿瘤鉴别诊断的准确率分别为８１８％和８９６％．对肝癌的敏感性分别为８６９％和９１３％．结论血清ＬＮ和ＣⅣ对良恶性肝肿瘤的鉴别诊断具有一定价值     

血清透明质酸与胃癌生物学的关系

目的研究透明质酸测定与胃癌生物学行为的关系及其临床意义．方法采用ＲＩＡ法测定胃癌（ｎ＝７９）、胃良性疾病（ｎ＝３７）和健康人（ｎ＝３０）血清中透明质酸水平，同时观察了胃癌术后患者血清透明质酸含量的变化．结果胃癌患者术前血清透明质酸水平（１２９５μｇ／Ｌ±８５６μｇ／Ｌ）明显高于正常人（３８７μｇ／Ｌ±２５２μｇ／Ｌ）和良性胃病患者（５０５μｇ／Ｌ±２５４μｇ／Ｌ，Ｐ＜００１），且与肿瘤大小和临床病理分期有关。癌肿切除后则明显降低（Ｐ＜００１）．结论血清透明质酸水平能在一定程度上反映胃癌生物学行为，并用于胃癌的诊断和治疗．     

测定血清脂质结合唾液酸对胃癌诊断的临床意义

临床检测结果：胃癌组血清脂质结合唾液酸（ＬＳＡ）含量（１４８±４７ｍｇ／Ｌ，ｎ＝４８）显著高于胃良性疾病（８８±２４ｍｇ／Ｌ，ｎ＝２９４）和正常值（８６±１２ｍｇ／Ｌ，ｎ＝２１０）（ｐ＜０．００１），测定ＬＳＡ对胃癌诊断敏感度７２．９％，特异度９１．８％，准确度８９．２％，诊断效率６６．９％，有明显应用价值。比较研究显示测定ＬＳＡ对胃癌诊断的价值优于血对癌胚抗原（ＣＥＡ）检测（Ｐ＜０．０１）．血清ＬＳＡ动态监测对胃癌术后复发或转移监视、疗效及预后分析等具有显著临床意义。     

间质性肺疾病支气管肺泡灌洗液中性粒细胞趋化因子和肿瘤坏死因子水平及其临床意义

目的探讨间质性肺疾病（ＩＬＤ）时中性粒细胞趋化因子（ＮＣＦ）和肿瘤坏死因子（ＴＮＦα）与ＩＬＤ活动性的关系。方法用膜滤过和放射免疫法检测１１例结节病、７例特发性肺间质纤维化（ＩＰＦ）患者和８名健康者血清及支气管肺泡灌洗液（ＢＡＬＦ）中ＮＣＦ活性及ＴＮＦα水平。结果７例ＩＰＦ患者ＢＡＬＦ中ＮＣＦ、ＴＮＦα分别为２０３±４４ｃｅｌｓ／１０ＨＰ、１１７±２９ｎｇ／Ｌ，明显高于８名对照组（８３±４５ｃｅｌｓ／１０ＨＰ、６５±１４ｎｇ／Ｌ、Ｐ＜０．０１）；１１例结节病患者ＢＡＬＦ中ＮＣＦ、ＴＮＦα分别为１８６±５０ｃｅｌｓ／１０ＨＰ、１２±３ｎｇ／Ｌ，明显高于８名对照组（Ｐ＜０．０１）。ＩＰＦ组ＢＡＬＦ中ＮＣＦ、ＴＮＦα均与中性粒细胞百分比呈正相关（ＮＣＦ：ｒ＝０．８９，Ｐ＜０．０１，ＴＮＦα：ｒ＝０．８６，Ｐ＜０．０５），结节病组ＢＡＬＦ中ＮＣＦ、ＴＮＦα均与淋巴细胞百分比呈正相关（ＮＣＦ：ｒ＝０．７８，Ｐ＜０．０１；ＴＮＦα：ｒ＝０．７３，Ｐ＜０．０１）。结论ＩＰＦ和结节病患者ＢＡＬＦ中ＮＣＦ、ＴＮＦα水平可做为肺泡炎活动性的标志     

糖尿病患者血清生长激素与肌酐清除率

测定了１６例胰岛素依赖型糖尿病（ＩＤＤＭ）患者，１９例非胰岛素依赖型糖尿病（ＮＩＤＤＭ）患者和２３例对照者的血清生长激素（ＧＨ）水平。在ＩＤＤＭ组，无论是肌酐清除率（Ｃｃｒ）正常或减低，其ＧＨ值均为２．５３±１．７３μｇ／Ｌ，均高于对照组的０．７１±０．５３μｇ／Ｌ（Ｐ＜０．０５），ＧＨ与Ｃｃｒ呈负相关（ｒ＝０．６３，Ｐ＜０．０１），ＮＩＤＤＭ组Ｃｃｒ＜５０ｍｌ／ｍｉｎ者ＧＨ值为１．８３±０．４７μｇ／Ｌ显著高于对照组（Ｐ＜０．０５）和Ｃｃｒ＞８０ｍｌ／ｍｉｎ组（ＧＨ０．８３±０．４９μｇ／Ｌ，Ｐ＜０．０５）。糖尿病（ＤＭ）伴微血管并发症者，ＧＨ值为２．９２±１．７０μｇ／Ｌ，高于无此并发症者ＧＨ１．２４±０．９７μｇ／Ｌ，（Ｐ＜０．０１），认为ＧＨ与ＤＭ微血管并发症有关。     

Comparative study of changing patterns of concanavalin A-binding proteins in early stage of cholesterol gallstone formation

AIM: To elucidate the importance and the changing patterns of biliary concanavalin A-binding proteins (CPs) in the early stage of cholesterol gallstone formation.METHODS: CP concentration and nucleation activity were measured by lectin affinity chromatography in bile samples of patients with cholesterol gallstones, pigment gallstones, gallbladder cholesterosis and non-biliary diseases.RESULTS: The concentrations of CPs were much higher in patients with cholesterol gallstones (0.39 ± 0.11 g/L, n = 36, P < 0.01) or gallbladder cholesterosis (0.40 ± 0.09 g/L, n = 9, P < 0.01) than in those with pigment gallstones (0.2 ± 0.12 g/L, n = 7) and/or non-biliary diseases (0.27 ± 0.09 g/L, n = 10). Pronucleating activities were much stronger in patients with cholesterol gallstones (nucleation time ratio: 0.57 ± 0.21, n = 5, P < 0.01 vs pigment gallstones and/or non biliary diseases) and gallbladder cholesterosis (nucleation time ratio: 0.44 ± 0.23, n = 5, P < 0.01 vs pigment gallstones or non-biliary diseases). The binding percentages of CPs to model biliary vesicles were also higher for patients with cholesterol gallstones (n = 6) than those with pigment gallstones (n = 6) (2.4% ± 0.9% vs 0.9% ± 0.5%, P < 0.01).CONCLUSION: Hypersecretion of CPs, especially those in vesicular phase, may be an important change in the early stage of cholesterol gallstone formation.     

High vesicular cholesterol and protein in bile are associated with formation of cholesterol but not pigment gallstones

To examine the differentiating parameters between cholesterol and pigment gallstones, we compared the nucleation times, concentrations of biliary lipid and protein, and the distribution of vesicular cholesterol in gallbladder bile of 16 patients with cholesterol, eight patients with black pigment gallstones, and nine gallstone-free control patients. Cholesterol monohydrate crystals were present in the fresh bile of only the cholesterol gallstone group. The nucleation time was significantly faster in the cholesterol stone group (3.3±3.2 days) than in the other two groups (pigment stone: 15.8±6.6, control: 16.9±5.7). The cholesterol saturation indices and the distribution of vesicular cholesterol were significantly higher in the cholesterol gallstone group than those in the other two groups. The total biliary protein concentration was significantly (P<0.01) higher in the cholesterol gallstone group [2.57±1.91 (sd) mg/ml] than that in the black pigment stone group (1.09±0.59). All parameters in patients with black pigment gallstone were essentially similar to the controls. We conclude that the presence of cholesterol crystals, rapid nucleation time, high vesicular cholesterol distribution, elevated cholesterol saturation index, and high protein concentration are associated with cholesterol gallstones but not with black pigment gallstones.     

Decreased protein concentration and improved metastability of bile induced by ursodeoxycholate

Previous studies demonstrated that higher biliary protein is associated with reduced metastability of bile. This study attempted to examine the induced effect of ursodeoxycholate on metastability of bile by measuring the nucleation time and biliary protein in cholesterol gallstone patients. Thirty-seven patients with functioning gallbladders were studied 10 control patients without gallstones and 27 with cholesterol gallstones. Ten of 27 cholesterol gallstone patients were treated with ursodeoxycholate (600 mg/ day) prior to surgery. Twelve of 17 untreated gallstone patients had cholesterol crystals in gallbladder bile while cholesterol crystals were absent in the ursodeoxycholate-treated gallstone patients and in the controls. Total protein concentration and cholesterol saturation index were significantly greater in the untreated gallstone patients with crystals than in those without crystals in bile. The treatment with ursodeoxycholate significantly decreased biliary protein concentration and cholesterol saturation index associated with the prolonged nucleation time. Cholesterol nucleation time correlated with biliary total protein concentration and cholesterol saturation index but not with total lipid concentration. It is concluded from the present study that ursodeoxycholate decreases biliary protein thereby partly increasing metastability of gallbladder bile.     

Decreased protein concentration and improved metastability of bile induced by ursodeoxycholate.

Previous studies demonstrated that higher biliary protein is associated with reduced metastability of bile. This study attempted to examine the induced effect of ursodeoxycholate on metastability of bile by measuring the nucleation time and biliary protein in cholesterol gallstone patients. Thirty-seven patients with functioning gallbladders were studied 10 control patients without gallstones and 27 with cholesterol gallstones. Ten of 27 cholesterol gallstone patients were treated with ursodeoxycholate (600 mg/day) prior to surgery. Twelve of 17 untreated gallstone patients had cholesterol crystals in gallbladder bile while cholesterol crystals were absent in the ursodeoxycholate-treated gallstone patients and in the controls. Total protein concentration and cholesterol saturation index were significantly greater in the untreated gallstone patients with crystals than in those without crystals in bile. The treatment with ursodeoxycholate significantly decreased biliary protein concentration and cholesterol saturation index associated with the prolonged nucleation time. Cholesterol nucleation time correlated with biliary total protein concentration and cholesterol saturation index but not with total lipid concentration. It is concluded from the present study that ursodeoxycholate decreases biliary protein thereby partly increasing metastability of gallbladder bile.     

Biliary proteins and the nucleation defect in cholesterol cholelithiasis

A study was performed to determine whether differences in gallbladder proteins might be present in patients with rapidly nucleating bile. Gallbladder and hepatic bile protein concentrations were measured using a fluorometric assay. The method was validated by an independent technique, i.e., hydrolysis and amino acid analysis. Persons with cholesterol gallstones had significantly higher gallbladder bile protein concentrations than patients without gallbladder disease or patients with pigment stones. The protein concentration correlated with the in vitro nucleation time in the cholesterol stone group. Gallbladder bile proteins were also purified by chromatography and gradient ultracentrifugation. Proteins from patients with cholesterol gallstones accelerated the nucleation time of control bile, whereas protein from controls had little effect. Hepatic bile protein concentrations were similar in persons with and without cholesterol gallstones. The gallbladder-to-hepatic bile ratios of a variety of solutes were examined. The ratio for protein in the cholesterol gallstone group can be explained straightforwardly by water reabsorption in the gallbladder, whereas the very low ratio in patients without cholesterol gallstones suggests that their gallbladders reduce protein mass by a process such as protein absorption or degradation during water absorption in the gallbladder.     

Increased biliary protein precedes gallstone formation

Although nucleation is critical to the pathogenesis of cholesterol gallstones, the factors responsible for this process are poorly defined. Numerous potential nucleating agents have been identified in the bile of humans and animals with cholelithiasis, including mucus, calcium, and bilirubin. Recent studies have shown that patients with cholesterol crystals and gallstones have increased biliary total protein, suggesting that protein may be a previously unrecognized nucleating factor. We tested the hypothesis that biliary total protein is increased prior to cholesterol gallstone formation. Prairie dogs were maintained on either control (N=22) or 0.4% cholesterol-enriched chow (N=18) for up to 18 weeks. Cholesterol-fed animals were classified as pregallstone (N=12) or gallstone (N=6) based on gross examination of the gallbladder bile. Both hepatic and gallbladder biles were then analyzed for lipid, bile acid, calcium, and protein content. Cholesterol feeding was associated with increased gallbladder concentrations of cholesterol, phospholipids, and calcium in the pregallstone and gallstone groups. Biliary total protein was significantly elevated in the pregallstone (5.8±0.4 mg/ml,P<0.001) and gallstone animals (6.0±0.6 mg/ml,P<0.001) as compared to controls (3.8±0.3 mg/ml). Regression analysis showed positive correlations between gallbladder bile total protein and the gallbladder bile cholesterol saturation index (CSI) (P<0.001), as well as between gallbladder total protein and calcium (P<0.001). Although the hepatic bile CSI was elevated in cholesterol-fed animals, total protein remained unchanged, suggesting that the alteration in biliary protein is a gallbladder phenomenon. The finding that gallbladder bile total protein increases during crystal agglomeration indicates that high concentrations of biliary total protein in combination with elevated levels of calcium may promote cholesterol crystal nucleation and gallstone formation.     

L-型钙通道α-1c亚型mRNA在结石胆囊组织的表达

目的研究不同类别结石胆囊组织L-型钙通道（Car1．2）mRNA的表达,探讨胆囊结石形成的可能分子机制及意义。方法应用RT-PCR半定量法分析胆色素结石、胆固醇结石、胆囊息肉的胆囊组织Car1．2mRNA的表达量。结果Cav1．2mRNA的表达在胆色素结石组和胆囊息肉组明显高于胆固醇结石组（P〈0．05）,但在胆色素结石组和息肉胆囊组之间差异无统计学意义（P〉0．05）。结论Cav1．2mRNA在胆色素结石、胆固醇结石、胆囊息肉三组胆囊组织中均有表达,并且在不同组别中的表达存在明显的差异,这种差异可能是钙离子通道在各类胆囊上分布差异的分子基础,在胆囊结石形成过程中起着重要作用。     

Effects of a concanavalin A-binding biliary glycoprotein on nucleation time of gallbladder bile

A study was performed to determine quantitative differences in the total protein concentration of gallbladder bile from gallstone patients and to isolate nucleation-promoting factors from the bile. Total protein concentrations in cholesterol gallstone bile (3.6±0.6 mg/ml, mean±SD, n=10), calcium bilirubinate gallstone bile (4.2±1.1 mg/ml, n=10), black pigment gallstone bile (1.9±0.6 mg/ml, n=4) and control gallbladder bile (2.3±0.5 mg/ml, n=9) were not significantly different. Also no statistically significant differences in cholesterol saturation index were found among these groups. Gallbladder bile from cholesterol gallstone patients showed significantly faster nucleation than that of contorls, calcium bilirubinate gallstone, or black pigment gallstone patients. We partially purified biliary glycoproteins from cholesterol gallstone bile or calcium bilirubinate gallstone bile by chromatography on concanavalin A Sepharose. Nucleation time was measured following the addition of these proteins to control bile in vitro. The glycoproteins obtained from cholesterol gallstone bile had significant nucleation-promoting activity, but nucleation time was not changed following the addition of biliary glycoproteins from calcium bilirubinate gallstone patients. These results suggest that qualitative differences in individual proteins of gallbladder bile are responsible for nucleation-promoting activity in vitro.     

Effects of a concanavalin A-binding biliary glycoprotein on nucleation time of gallbladder bile

A study was performed to determine quantitative differences in the total protein concentration of gallbladder bile from gallstone patients and to isolate nucleation-promoting factors from the bile. Total protein concentrations in cholesterol gallstone bile (3.6 +/- 0.6 mg/ml, mean +/- SD, n = 10), calcium bilirubinate gallstone bile (4.2 +/- 1.1 mg/ml, n = 10), black pigment gallstone bile (1.9 +/- 0.6 mg/ml, n = 4) and control gallbladder bile (2.3 +/- 0.5 mg/ml, n = 9) were not significantly different. Also no statistically significant differences in cholesterol saturation index were found among these groups. Gallbladder bile from cholesterol gallstone patients showed significantly faster nucleation than that of controls, calcium bilirubinate gallstone, or black pigment gallstone patients. We partially purified biliary glycoproteins proteins from cholesterol gallstone bile or calcium bilirubinate gallstone bile by chromatography on concanavalin A Sepharose. Nucleation time was measured following the addition of these proteins to control bile in vitro. The glycoproteins obtained from cholesterol gallstone bile had significant nucleation-promoting activity, but nucleation time was not changed following the addition of biliary glycoproteins from calcium bilirubinate gallstone patients. These results suggest that qualitative differences in individual proteins of gallbladder bile are responsible for nucleation-promoting activity in vitro.     

Cholesterol and pigment gallstone disease: comparison of the reliability of three bile tests for differentiation between the two stone types

Gallbladder biles and stones were obtained at 116 cholecystectomies for symptomatic gallstone disease. All 33 patients younger than 50 years had cholesterol stones, whereas 40% of the older patients had pigment stones. We compared the reliability of three different bile tests for the differentiation between cholesterol and pigment stone patients. Whereas both the presence of cholesterol monohydrate crystals in fresh gallbladder bile and a nucleation time less than or equal to 20 days in ultrafiltered gallbladder bile had a specificity of 100% for cholesterol gallstone disease, biliary supersaturation with cholesterol (cholesterol saturation index greater than 1.0) had a low specificity. The sensitivity of nucleation time less than or equal to 20 days for cholesterol gallstone disease was 78% in concentrated gallbladder biles (biliary total lipid concentration greater than or equal to 5 g/dl) but only 21% in dilute biles (biliary total lipid concentration less than 5 g/dl). In contrast, examination for the presence of cholesterol crystals in fresh bile was reasonably sensitive both in concentrated and dilute gallbladder biles (sensitivity, 84% and 72%, respectively). In addition, duodenal bile obtained from 16 patients (10 cholesterol, 6 pigment) before cholecystectomy showed cholesterol crystals in 7 of the cholesterol but in none of the pigment stone patients. We conclude that examination of fresh bile for cholesterol crystals is a specific and reasonably sensitive test for cholesterol gallstone disease.