肝细胞癌和肝硬化组织中增殖细胞核抗原及Ki-67抗原的表达及意义

为探讨肝细胞癌 (HCC)和肝硬化组织中增殖细胞核抗原 (PCNA)及 Ki- 67抗原的表达及意义 ,采用免疫组织化学技术检测 PCNA和 Ki- 67抗原在 HCC和肝硬化组织中的标记指数 (L I)。结果显示 , 、 、 级 HCC的 PCNA L I分别为 (2 6.9± 17.4) %、 (3 3 .1± 2 2 .7) %、 (73 .8± 16.3 ) % ,各级之间差异均有显著性(P均 <0 .0 5 ) ;Ki- 67L I分别为 (2 5 .8± 15 .6) %、 (5 8.2± 18.6) %、 (75 .3± 2 0 .2 ) % ,各级之间差异均有显著性 (P均 <0 .0 5 ) ;但各级 HCC中的 PCNA L I和 Ki- 67L I差异均无显著性 (P均 >0 .0 5 )。肝硬化组织中 PCNAL I为 (8.8± 5 .2 ) % ,Ki- 67L I为 (7.9± 4.4) % ,两者之间差异无显著性 (P>0 .0 5 )。提示 HCC及肝硬化组织中 PCNA和 Ki- 67抗原的阳性率基本一致 ,HCC的分化程度与 PCNA或 Ki- 67密切相关 ;原位检测 HCC组织中PCNA或 Ki- 67抗原的表达 ,有助于判断 HCC分化程度及预后     

胶质瘤IDH1基因变异与Ki-67、微血管密度表达的相关性

目的探讨胶质瘤IDH1基因变异对组织中抗原Ki-67及微血管密度(MVD)表达的影响及IDH1基因变异延长患者生存期的机制。方法运用SP法分别进行Ki-67、CD34的免疫组织化学染色检测胶质瘤IDH1变异组及未变异组抗原Ki-67标记指数(LI)及MVD计数。结果变异组Ki-67蛋白表达较未变异组降低(t=2.134,P=0.039),变异组与未变异组Ki-67 LI分别为(14.44%±8.23%)和(21.19%±11.49%);变异组MVD较未变异组减低(t=2.328,P=0.025),其MVD分别为31.11±13.47和40.54±12.11;低级别胶质瘤Ki-67及MVD表达较高级别胶质瘤低(t=9.138,P<0.001;t=-8.369,P<0.001),低级别胶质瘤(WHOⅠ级、Ⅱ级)和高级别胶质瘤(WHOⅢ级、Ⅳ级)Ki-67表达分别是8.36%±2.84%和25.55%±7.53%,其MVD分别为23.94±8.03和45.54±8.19,两者表达随胶质瘤级别增高而增高。结论胶质瘤IDH1基因变异对肿瘤细胞的增殖有影响,IDH1基因变异影响肿瘤的能量代谢,而能量代谢受阻降低细胞的增殖活性,使大量细胞处于休眠期,导致新生血管内皮细胞分裂缓慢,新生肿瘤血管数量减低,恶变和转移受到抑制,为IDH1基因变异延长患者的生存期的机制提供新的理论依据。     

Expression and prognostic role of molecular markers in 99 KIT-positive gastric stromal tumors in Taiwanese

AIM:To elucidate the prognostic role and relationship ofthree molecular markers such as tumor suppressor genep53,proliferating cell nuclear antigen(PCNA)and Ki-67in gastric stromal tumor.METHODS:A total of 108 surgically resected gastricsmooth muscle tumor specimens were collected fromJanuary 1987 to December 1999.Immunohistochemicalstudies were performed on the paraffin sections of 99of 108 CD117-positive tumors with antibodies of p53,PCNA,and Ki-67.Immunoreactivity of three molecularmarkers was recorded by labeling index(LI,%)and wasanalyzed for clinicopathologic and survival correlation.RESULTS:Of the 99 cases,immunostaining revealedthat 52 patients(52.5%)had p53,and 37 patients(37.3%)had Ki-67 immunoreactivity(defined as>10%of LI).All patients(100%)had PCNA immunoreactivityranging from 12% to 93% of LI,divided into high orlow by median.Statistics revealed that LI of threemarkers positively correlate to each other(P<0.01)and to microscopic tumor mitotic counts(P<0.001).By combination,patients with≥2 markers(positiveor high)in tumors had early tumor recurrence(P<0.001)and unfavorable outcome(P<0.001).Univariate analysis indicated that patients with tumorsize>5 cm(P=0.003),tumor mitosis>5/50 HPF(P<0.001),p53 immunoreacUvity(P=0.001),Ki-67 immunoreactivity(P=0.026),high PCNA LI(P=0.015)and male gender(P=0.036)were six predictors for earlydisease recurrence.Subsequent multivariate analysisrevealed that mitotic counts,tumor size,and p53immunoreactivity were three independent prognosticfactors for both disease free and overall survival ofpatients.By combination of three independent prognosticfactors for grouping,we found higher tumor recurrencerate(P<0.001)and shorter survival(P<0.001)existed ingroups with increasing factors.CONCLUSION:We first provide the prognostic valueand linkage of three molecular markers in GISTs.Thecombination of three factors(p53,tumor size,andtumor mitosis)provides a more powerful prediction ofprognosis than any single factor does.     

Survivin蛋白在前列腺癌组织中的表达和相关性研究

目的探讨Survivin蛋白在前列腺癌组织中表达及其与肿瘤增殖、微血管密度计数和肿瘤细胞凋亡的关系和临床意义。方法采用免疫组化SP法和DNA原位未端标记TUNEL法分别测定42例前列腺癌(PCa)组织和10例正常前列腺(NP)组织中Survivin、Ki-67、VEGF、CD34的表达和细胞凋亡情况。结果Survivin蛋白在PCa中的阳性表达为80.59%,与病理分级、临床分期和淋巴结转移密切相关(P<0.05),而正常前列腺组织中无阳性表达。Ki-67标记指数(LI)在PCa及NP中分别为(14.42±8.10)%和(8.10±2.50)%,其差异有统计学意义(P<0.01)。PCa中VEGF的阳性表达为69.05%,与病理分级、临床分期和淋巴结转移密切相关(P<0.05)。PCa中MVD计数(32.54±10.17)显著高于正常前列腺组织(19.68±5.14)(P<0.01)。PCa癌组织及NP组织中细胞凋亡指数(AI)分别为3.03±1.33和1.07±0.77,其差异有统计学意义(P<0.05)。Survivin蛋白的表达与Ki-67LI、VEGF、MVD计数呈正相关(r分别为0.828、0.427和0.386,P<0.05);Survivin蛋白的表达与细胞凋亡指数呈负相关(r=-0.679,P<0.001)。结论Survivin蛋白的异常表达而引起的细胞凋亡抑制或逃避、肿瘤细胞增殖和微血管增生的增加,在前列腺癌的发生、发展中起一定的作用;Survivin蛋白的检测有助于对肿瘤细胞的分化程度、病理分期作出正确评价,以指导临床治疗及估计预后。     

原发性胆囊癌组织中脆性组氨酸三联体基因和Ki-67的表达及临床意义

目的:探讨脆性组氨酸三联体(FHIT)基因和Ki-67抗原在原发性胆囊癌、胆囊腺瘤和慢性胆囊炎组织中的表达情况.方法:应用免疫组织化学S-P法,检测51例原发性胆囊癌、15例胆囊腺瘤和12例慢性胆囊炎组织中FHIT和Ki-67的表达情况,并分析其与胆囊癌临床病理因素的关系.结果:胆囊癌组中FHIT阳性率明显低于胆囊腺瘤和慢性胆囊炎组(47.1%vs66.7%,91.7%,P<0.01),而Ki-67阳性率明显高于胆囊腺瘤和慢性胆囊炎组(82.4%vs20.0%,0,P<0.01).FHIT表达缺失不仅与胆囊癌的高分级(18.8%vs56.5%,66.7%,P=0.02)、淋巴结或远处转移(33.3%vs66.7%,P=0.019)明显相关,而且与术后生存时间减少关系密切(31.2%vs77.8%,P=0.041).Ki-67表达与胆囊癌的高分级(58.3%vs87.0%,93.8%,P=0.039)和淋巴结或远处转移(33.3%vs66.7%,P=0.037)明显相关.FHIT与Ki-67表达呈负相关(r=-0.285,P=0.043).结论:FHIT基因是胆囊癌的一个候选抑癌基因.FHIT和Ki-67在胆囊癌的发生和演化中均起着重要作用,联合检测FHIT和Ki-67的表达情况有助于临床评估胆囊癌的生物学行为和判断预后.     

MCM5和Ki-67在前列腺癌组织中的表达及意义

目的探讨微小染色体维持蛋白5(MCM5)和细胞增殖核抗原(Ki-67)在前列腺癌发生、发展中的作用。方法选择穿刺及手术切除的前列腺癌组织标本50份(肿瘤组)及良性前列腺增生组织15份(增生组),采用免疫组化技术检测两组MCM5、Ki-67的阳性表达情况[以标记指数(LI)表示],并分析两者间及与前列腺癌临床病理参数的相关性。结果肿瘤组MCM5、Ki-67的LI均明显高于增生组,P均<0.05;MCM5、Ki-67阳性表达与前列腺癌病理分级、临床分期均有相关性;前列腺癌组织中MCM5与Ki-67阳性表达呈正相关。结论 MCM5蛋白是前列腺癌组织的一种新的可靠增殖标志物,其表达水平与前列腺癌的发生、发展密切相关。     

组织芯片技术研究食管胃黏膜病变中Ki-67的表达及其与细胞增殖和凋亡的关系

背景：近20年来食管和食管胃连接处（EGJ）腺癌发生率呈上升趋势,Barrett食管（BE）被认为是其发生的重要危险因素。目的：应用组织芯片技术研究Ki-67在各类食管胃黏膜病变中的表达及其与细胞增殖和凋亡的关系。方法：制作140例各类食管胃黏膜组织的组织芯片,结合免疫组化方法检测Ki-67和增殖细胞核抗原（PCNA）表达。以原位末端标记技术（TUNEL法）检测BE、食管腺癌和贲门癌的细胞凋亡情况。结果：BE、食管腺癌和贲门癌组Ki-67阳性率分别为40.9%、69.6%和61.9%,均显著高于正常贲门组织（0.0%,P〈0.01）和贲门肠化生（IM）组（11.5%,P〈0.05）。BE、贲门IM、胃窦IM、食管腺癌和贲门癌组PCNA阳性率均显著高于正常贲门组织（45.5%、42.3%、39.3%、52.2%和42.9%对10.0%,P〈0.05）。BE、食管腺癌和贲门癌中Ki-67表达弱阳性和阳性者细胞凋亡指数均较表达阴性者显著降低（P〈0.05）,而PCNA仅表达阳性者凋亡指数较表达阴性者显著降低（P〈0.05）。结论：BE和EGJ处肿瘤的发生与Ki-67表达异常有关,Ki-67较PCNA更能反映EGJ处细胞凋亡状态。     

四氯化碳诱发大鼠肝纤维化自发逆转中库普弗细胞与星状细胞的分布

目的:探讨四氯化碳(CCl_4)诱发大鼠肝纤维化自发逆转过程中肝库普弗细胞与星状细胞的分布和意义.方法:500 mL/L CCl_4腹腔注射8 wk诱发大鼠肝纤维化模型,实验第8,12周末检测血清生化指标,观察肝组织的病理变化,采用免疫组化SP法观察单核巨噬细胞抗原(ED1),α-平滑肌动蛋白(α-SMA)阳性表达的肝库普弗细胞(kupffer cell,KC)和肝星状细胞(hepatic stellate cells,HSC)的分布结果:第8周末模型组大鼠与对照组比较,血清ALT和AST活性(568.18±630.46 nkat/L vs 472.26±167.37 nkat/L.P<0.05:5845.84±1353.27 nkat/L vs 1698.51±663.30 nkat/L.P<0.01),肝/体质比(3.90±0.85 vs 2.56±0.24,P<0.001)及胶原纤维面密度(5.87±1.13 vs 0.52±0.30,P<0.001)明显增高;大量ED1和α-SMA阳性的KC和HSC主要分布在汇管区增生的纤维组织及纤维间隔内.第12周末模型组与第8周比较大鼠血清ALT活性(1020.70±306.73 nkat/L vs 376.74±304.06 nkat/L.P<0.05)仍较高外,胶原纤维面密度减少,汇管区增生的纤维组织及纤维间隔内ED1阳性的KC减少,α-SMA阳性的HSC消失.结论:腹腔注射CCl_48 wk后大鼠肝功能明显损伤,形成肝硬化,KCs激活和HSCs活化相关,停止注射CCl_4 4 wk后大鼠肝纤维化发生自发逆转.     

p38丝裂原活化蛋白激酶和乙型肝炎病毒X蛋白在人肝癌发生中对细胞增殖和凋亡的作用

目的 研究人肝癌发生过程中p38MAPK和乙型肝炎病毒X蛋白(HBX)对细胞增殖和凋亡的影响,探讨肝癌发生的机制. 方法 应用免疫组织化学和DNA原位末端标记(TUNEL)法原位检测人肝癌(36例)和相关慢性肝病组织(慢性乙型肝炎、肝硬化和癌周肝硬化分别为20、20、36例)的p38MAPK、HBX、细胞周期G2/M期相关因子(cdc25B,p34cdc2,细胞周期蛋白B1)、细胞增殖因子Ki-67和细胞凋亡情况.根据资料不同分别采用x2检验、One-Way ANOVA或t检验进行统计学处理. 结果 HBX在慢性乙型肝炎(65.0％)和肝癌组(44.4％)阳性率较高,主要表达于胞核; p38MAPK、cdc25B、细胞周期蛋白B1、p34cdc2的阳性率从正常肝组织(40.0％,20.0％,20.0％,30.0％)、慢性乙型肝炎(60.0％,65.0％,40.0％,50.0％)、肝硬化(65.0％,75.0％,70.0％,55.0％)、癌周肝硬化(66.7％,75.0％,75.0％,63.9％)到肝癌组(77.8％,80.6％,80.6％,72.2％)逐渐增高,表达部位发生改变.p38MAPK胞核表达主要见于慢性乙型肝炎组和肝硬化组,胞质表达见于癌周肝硬化组和肝癌组,癌周肝硬化组与肝癌组之间的差异无统计学意义(x2=1.11,P＞0.05).正常肝、慢性乙型肝炎、肝硬化、癌周肝硬化和肝癌组织中的增殖指数(0.0000±0.000,0.0502±0.011,0.0411±0.009,0.0762±0.017,0.1810±0.036)和凋亡指数(0.0351±0.024,0.0607±0.022,0.0562±0.013,0.0716±0.011,0.1200±0.018)比较,除肝硬化外也逐渐增高,增殖指数在肝癌分化差组(0.2285±0.062)高于分化好组(0.1216±0.032,t=2.082,P=0.044),凋亡指数肝癌在分化好组(0.152±0.026)高于分化差组(0.081±0.022,t=2.129,P=0.041).结论 肝癌发生过程中,HBX可能通过p38MAPK通路引起细胞周期、细胞增殖和凋亡的异常改变.细胞增殖基本与凋亡相伴随,肝癌增殖程度高于凋亡程度.癌周肝硬化不同于不伴癌的肝硬化,与肝癌的关系更密切.     

Fibroscan在慢性肝病中的临床应用分析

目的分析瞬时弹性扫描仪(Fibroscan)在慢性乙型肝炎、慢性丙型肝炎、乙型肝炎肝硬化及丙型肝炎肝硬化四种不同慢性肝病中检测的cut-off值对肝纤维化测量的准确性及影响因素。方法我院2009年4月-2010年6月临床诊断的肝病患者共1 458例,其中慢性乙型肝炎398例、慢性丙型肝炎446例、乙型肝炎肝硬化438例、丙型肝炎肝硬化176例,分别行Fibroscan测量cut-off值,分析其在不同肝病符合率及可能影响因素。结果 Fibroscan检查的cut-off值以12.4 KPa为分界线,通过与临床诊断对比,Fibroscan检查在慢性丙型肝炎、慢性乙型肝炎、丙型肝炎肝硬化、乙型肝炎肝硬化诊断符合率分别为94.17%、70.60%、85.80%、85.39%。其中在丙肝和乙肝诊断符合率方面有显著差异(P<0.05);117例慢乙肝患者的Fibroscan检测的cut-off值与临床诊断不符合,其中34例患者BMI﹥25 kg/m2,占29.06%;74例肝功能ALT﹥80 U/L,占63.25%。结论 Fibroscan可协助诊断慢性肝病,尤其在慢性丙肝诊断方面意义重大。肥胖和肝脏炎症活动是影响Fibroscan检测结果的重要因素,合适人群的界定、恰当时机的选择对提高Fibroscan检测准确性具有重大意义。     

Carcinoembryonic antigen

The level of carcinoembryonic antigen (CEA) is often elevated in the serum of patients with cancer. This article reviews the clinical usefulness of this observation. Carcinoembryonic antigen is not useful for detecting asymptomatic cancer; its sensitivity and specificity are not high, particularly for early stages of disease, so in populations with low prevalence of disease there are many false-positive and false-negative results. Similarly, the antigen level cannot, by itself, provide enough diagnostic certainty to confirm or rule out suspected cancer. For some cancers, antigen levels at the time of diagnosis provide more precise prognosis than staging alone, but this information does not lead to more effective treatment. Serial measurement of CEA levels after surgery in patients with colorectal cancer can detect recurrences early, but few lives can be saved by this approach. Thus, CEA assays provide accurate information about some aspects of cancer but rarely lead to better outcomes for patients.     

Co-expression of X-hapten-like antigen and antigen YH206 on mucin molecules

The asialocarbohydrate antigen YH206 is expressed on adenocarcinoma-associated mucin molecules which lack epitopes of CA19-9 and DU-PAN-2. To further characterize this molecule, the monoclonal antibody BM2 against the affinity-purified antigen YH206 was established. It was demonstrated by an inhibition test that antigen BM2 was an X-hapten-like structure, one of the representative oncodevelopmental antigens. Although the sensitivity of antigen BM2 in sera of stomach and pancreas cancer patients did not appear to be superior to that of antigen YH206, both antigens were complementary to each other resulting in the improvement of sensitivity. Interestingly, double-determinant enzyme immunoassays showed that antigen BM2 and YH206, both having a cryptic nature for neuraminidase, were co-expressed on the same mucin molecule in sera of patients with stomach cancer or liver cirrhosis. These data suggest that mucin molecules in serum might be classified into several groups based on the distribution of tumor-associated epitopes. This work was supported by Grant-in-Aid for Cancer Research from the Ministry of Education, Science and culture (A. Yachi, 01010054). and from the Ministry of Health and Welfare. Japan     

Carcinoembryonic antigen

Recent data would limit indications for serum CEA measurement primarily to follow-up of resected colonic malignancy, yet physician attitude and usage patterns may lag far behind current findings. This discrepancy was investigated at our institution, where more than 1100 CEAs costing $71,000 are ordered each year. Of 45 physicians (all MDs ordering a CEA test during a preselected month), over 50% believed the test to be worthwhile in initial detection of colonic cancer, and 69% thought an elevated CEA to be an adequate reason to begin an aggressive workup to rule out cancer of the colon in a nonsmoking, previously healthy patient. Impressions of cost were $30 (50% of true cost) in nearly half of MDs and 20% of true cost in a tenth of MDs. Analysis of the medical record revealed that indications of questionable validity (initial detection of cancer together with follow-up of noncolonic malignancy) accounted for the majority of requested CEAs and included the attempted detection or monitoring of 12 different tumor types in addition to its use as a general cancer screen. Patient benefit was realized in none in a random sample of 106 cases (=0.11, power =0.89 for an assumed benefit of 2%), while management was altered in only one patient as a direct result of the CEA value. It is important that we continue to inform and educate our colleagues about relatively expensive tests that have only limited and specific application.Supported by U.S. Public Health Service grant AM20201 and a Career Development Award from the National Foundation for Ileitis and Colitis.Presented in part at the American Gastroenterological Association Meeting, May 1980, Salt Lake City, Utah.     

Preparation of Toxoplasma gondii RH strain antigen,antigen analysis and antigen detection in sera: a review

The prevalence of antibodies detected by serology against Toxoplasma gondii in Indonesia is quite high. Therefore further research concerning the antigen used is important to improve the quality of the assay being used with lower cost. An attempt to prepare T. gondii strain RH antigen followed by using it in the ELISA procedure for detecting IgG showed that there was no significant difference between the local ELISA and Toxonostika quantitatively and qualitatively. Analysis of the antigen was done by Western blot, using sera collected from 30 clinically suspected toxoplasmosis cases which contained IgG only (titer ranging from 1:1,600-> or = 1:3,200); from 9 asymptomatic healthy person, from 5 cases consisted of 1 case of lymphadenitis (IgM titer > or = 1:3200 and IgG titer 1:800) and 4 cases of visual disturbances which had IgM with titer ranging from 1:800 to > or = 1:3,200 and IgG with titer ranging from 1:800 to > or = 1:3,200. It was shown that antigen components of 90, 87, 82, 72, 41, 26 and < or = 6 kDa reacted to all sera containing IgG except sera containing both IgG and IgM. Especially bands of 41 and 26 kDa showed strong reaction with all sera containing IgG, except 2 sera which contained both IgG (titer 1:800) and IgM (titer 1:800 and 1:3,200). These sera collected from 2 left eye vision disturbance cases were not reactive to all antigen components. Strong reactions against bands of 41, 26 and < or = 6 kDa were also shown in sera which contained only IgG collected from 9 healthy persons without any toxoplasmosis symptoms whereas bands of 90, 87, 82 and 72 kDa all showed moderate strong reaction. Contrasting to sera containing only IgG, of 5 sera containing both IgG and IgM 3 of them showed only reactions against bands of 41, 26 and < or = 6 kDa which were strong. It seemed that almost all sera containing IgG gave reaction to 90, 87, 82, 72, 41, 26 and < or = 6 kDa, however different pattern of reaction might occur, probably depending on the nature of infection as more antigen components would be recognized by sera containing IgG alone rather than sera containing both IgM in large quantity and IgG. In another study, an attempt to detect T. gondii antigen in 60 samples was done by using ELISA, and it was shown that circulating antigen was found in 27 (90%) from 30 samples which contained both IgG and IgM, whereas only 2 (66%) from 30 samples which contained only IgG showed positive results. Therefore, antigen detection can be used to identify the acute phase of infection.     

Subspecificities of Australia antigen

Subtyping of HBAg was carried out in 100 subjects at the Gastroenterology Laboratory of the All-India Institute of Medical Sciences using agar-gel diffusion and counterelectrophoresis techniques. All sera were positive for thea determinant. Of the total, 67 subjects were positive for they determinant and 33 for thed determinant. Similar relative distribution of subtypes was found in cases of hepatitis and carriers. However, on evaluating the hepatitis group alone, a significant predominance of subtypeay was found in cases of acute hepatitis and subtypead in cases of chronic hepatitis. This implies that infection with hepatitis B virus of subtypead is more likely to lead to the sequelae of chronic hepatitis.     

弓形虫排泄-分泌抗原和可溶性速殖子抗原免疫原性的观察

目的观察弓形虫速殖子排泄-分泌抗原（excreted/secreted antigen,ESA）和可溶性速殖子抗原（soluble tachyzoite antigen,STAg）鼻内免疫小鼠的免疫原性。方法BALB/c小鼠随机分为4组,分别用PBS 20μl/只、体外排泄-分泌抗原（excreted/secreted antigenin vitro,ESAv）、腹腔排泄-分泌抗原（excreted/secreted antigen in mice,ESAm）和STAg各20μg/只鼻内免疫2次,间隔14 d。分别于末次免疫后14 d和44 d每组处死8只小鼠,计数肠上皮内淋巴细胞（intestinal intraepithelial lymphocytes,iIEL）和脾淋巴细胞,ELISA法检测血清IgG和小肠冲洗液sIgA抗体水平。结果实验期间,ESAm组小鼠于二次免疫后状态欠佳,其他各组小鼠健康状况良好。末次免疫后14 d,各抗原组脾淋巴细胞及iIEL均增殖活跃,细胞数与PBS组比较,差异具统计学意义（P〈0.05或P〈0.01）;至免疫后44 d,两种ESA组脾淋巴细胞及iIEL数与PBS组比较差异具统计学意义（P〈0.05）。各抗原组血清IgG水平在免疫后14 d和44 d均明显增高,与PBS组比较差异有统计学意义（P〈0.05或P〈0.01）。免疫后14 d肠液sIgA水平ESAv、ES-Am和STAg组与PBS组比较差异有统计学意义（P〈0.05或P〈0.01）,ESAm和STAg组与ESAv组比较差异有统计学意义（P〈0.05或P〈0.01）,两种ESA组在免疫后44 d与PBS组比较差异仍具统计学意义（P〈0.05）。结论ESAv、ESAm和STAg鼻内免疫均可诱导粘膜及系统的细胞和体液免疫应答,有较强的免疫原性。但ESAm可能对机体有毒副作用,不适宜直接鼻内免疫。     

Assessment of Dharmendra antigen. III. Comparative study with Mitsuda antigen

Four fractions each from Dharmendra and Mitsuda antigen have been obtained by step-wise centrifugation and sonication of the antigen. These fractions have been assessed for their capacity of inducing skin delayed hypersensitivity response. While, it has been noted that all fractions of both types of antigens can induce a good early reaction, the late skin reaction is only mounted by intact bacilli of both types of antigen. When compared at a constant bacillary concentration, Dharmendra antigen has produced better early skin reaction than Mitsuda antigen, whereas the intensity of late skin reaction is almost equal with both the antigens. The hypothesis has been put forward that the early, as well as the late reaction are produced by the same antigen and this antigen is located in the protoplasm of M. leprae.