Molecular mechanisms underlying IFN-{gamma}-mediated tumor growth inhibition induced during tumor growth inhibition induced during tumor immunotherapy with rIL-12

The present studnt Investigates the molecular by which IFN-produced as a result of in vitroIL-12 addministration exertsits anty-tumor,rIL-12 was administered three or five times intomice bearing CDA1M fibrosarcoma, OV-HM ovarian carcinoma orMCH-1-A1 fibosarcoma. This regimen induced complete regressionof CSA1M and OV-HM tumors but only transient growth inhibitionof MCH-1-A1 tumors. The anty-tumor effects of Il-12 were associatatedwith enhanced induction of IFN-becouse these effects were abrogatedby pretreatment of hosts with anti-IFN- antibody.Exposure inin vitro of the three types of tumor cells to rIFN- resultedin moderate to potent inhibition of tumor cell growth.IFNstimulatedthe expression of mRNAs for an inducible type of NO synthasa(INOS)in CSA1M cells and indoleamine 2,3-dioxygenasa (IDO),an enzyme capable of degrading tryptophan, in OV-HM cells ,but induced only marginal levels of these mRNAs in MCH-I-ALcells. In association withiNOS gene expression, INF--stimulatedCSA1M cells produced a large amount of NO which functioned toinhibit their own growth in vitro. Although OV-HM and MCH-1-A1cells did not produce NO, they also exhibited NO susceptibility.Whereasthe tumor masses from IL-12-treated CSA1M-bearing mice inducedhigher levels of INOS (for CSA1M) or IDO and iNOS (for OV-HM)mRNAs,the MCH-1-A1 tumor mass expressed lower levels of iNOS mRNAalone.Moreover, massive infiltration of CD4⁺and CD8⁺ T cellsand Mac-1⁺ cells was seen only in the CSA1M and OV-HM tumors.Thus, these results indicate that IFN- produced after IL-12treatment induces the expression of various genes with potentialto modulate tumor cells and growth by acting directly on tumorecells or stimulating tumor-infiltrating lymphold cells and thatthe effectiveness of IL12 therapy is assoiated with the operation if these mechanisms.     

Distinct roles of type I bone morphogenetic protein receptors in the formation and differentiation of cartilage

The bone morphogenetic proteins (BMPs), TGFβ superfamily members, play diverse roles in embryogenesis, but how the BMPs exert their action is unclear and how different BMP receptors (BMPRs) contribute to this process is not known. Here we demonstrate that the two type I BMPRs, BMPR-IA and BMPR-IB, regulate distinct processes during chick limb development. BmpR-IB expression in the embryonic limb prefigures the future cartilage primordium, and its activity is necessary for the initial steps of chondrogenesis. During later chondrogenesis, BmpR-IA is specifically expressed in prehypertrophic chondrocytes. BMPR-IA regulates chondrocyte differentiation, serving as a downstream mediator of Indian Hedgehog (IHH) function in both a local signaling loop and a longer-range relay system to PTHrP. BMPR-IB also regulates apoptosis: Expression of activated BMPR-IB results in increased cell death, and we showed previously that dominant-negative BMPR-IB inhibits apoptosis. Our studies indicate that in TGFβ signaling systems, different type I receptor isoforms are dedicated to specific functions during embryogenesis.     

Creutzfeldt-Jakob disease (CJD) with a mutation at codon 148 of prion protein gene: relationship with sporadic CJD

Creutzfeldt-Jakob disease (CJD), the most common human prion disease, includes sporadic (s) and familial (f) forms. Regardless of etiology, both forms are thought to share the pathogenic mechanism whereby the cellular prion protein (PrP(C)) converts into its pathogenic isoform (PrP(Sc)). While PrP(C) conversion is thought to be random in sCJD, conversion in fCJD is facilitated by the congenital presence of mutated PrP. Differences in PrP genotype (PRNP) and in conversion circumstances lead to PrP(Sc) with distinct characteristics that elicit different disease phenotypes. Here, we describe a case of fCJD with a substitution of histidine (H) for arginine (R) at codon 148 (R148H) and heterozygosity of the methionine/valine (M/V) polymorphic codon 129, with the 129M allele coupled with the mutation. The disease phenotype and all major characteristics of PrP(Sc) of fCJD(R148H) were virtually indistinguishable from those of sCJDMV2, which has features different from those of any other sCJD. Therefore, despite the differences in etiology, PRNP, and conversion process, the two forms of PrP(Sc) had similar characteristics. Furthermore, comparison of fCJD(R148H) with a recently reported case carrying R148H and homozygosity at codon 129 suggests that codon 129 coupled with the mutation as well as that located on the normal allele can modify major phenotypic and PrP(Sc) features of fCJD(R148H).     

Ⅲ型胶原肾小球病的形态学观察

目的了解Ⅲ型胶原肾小球病的形态学改变,并对Ⅲ型胶原可能的细胞来源进行初步探讨。方法对3例肾活检组织进行光镜、免疫荧光、电镜和Ⅰ、Ⅲ、Ⅳ型胶原及d平滑肌肌动蛋白(α-SMA)的免疫组织化学染色(SP法)观察。结果2例患者临床表现为肾病综合征,其中1例伴高血压,第3例表现为肾功能不全和肾性高血压。3例均无肾病家族史。光镜检查可见肾小球基膜内和系膜区弥漫性过碘酸-希夫反应阳性物质沉积,系膜细胞无明显增生。电镜检查在基膜内疏松层和系膜区可见大量胶原纤维沉积,系膜细胞胞膜下平行排列的束状微丝明显增加。免疫组织化学显示这些胶原纤维为Ⅲ型胶原,Ⅰ型和Ⅳ型胶原阴性,同时系膜区多数系膜细胞α-SMA阳性。结论Ⅲ型胶原肾小球病光镜、电镜及免疫组织化学上都有其特殊的病理改变。肾小球内激活的系膜细胞可能是Ⅲ型胶原的来源。     

肿瘤坏死因子与肾小球系膜细胞的关系

目的研究肾小球系膜细胞的肿瘤坏死因子的自分泌功能,肿瘤坏死因子对肾小球系膜细胞作用的机制。方法利用体外培养的人和大鼠的肾小球系膜细胞,通过逆转录－多聚酶链反应、原位杂交和免疫组化方法,探讨它们之间的关系。结果肾小球系膜细胞既可产生肿瘤坏死因子,又有肿瘤坏死因子受体。结论肾小球系膜细胞是肿瘤坏死因子作用的靶细胞,肿瘤坏死因子通过旁分泌和自分泌两种途径作用于肾小球系膜细胞。     

电化学治疗昆明小鼠肉瘤及其机理分析

研究了电化学治疗昆明小鼠肉瘤的疗效,并分析其机理。在体外将S-180细胞用不同参数的电场处理,研究适合电化学治疗的电场条件。通过复制肉瘤模型,将肉瘤小鼠随机分成4组:对照组、电疗组、化疗组、电化疗组。研究了不同处理组的肿瘤抑瘤率、治愈率以及小鼠的自由基代谢水平。结果电化疗组的抑瘤率、治愈率都显著高于化疗组和电疗组(P<0.05),电化疗组小鼠受到氧自由基的攻击显著降低,免疫力提高。分析机理发现,电化学治疗肿瘤的机理可能至少涉及细胞膜通透性提高、细胞的耐药性降低、机体的免疫力提高三个方面。     

电脉冲致离体S-180细胞电穿孔的观察与研究

扫描电镜下我们观察到了一定强度电脉冲致 S- 180细胞电穿孔的现象。同时分别改变电压、电容、脉冲个数 ,对 S- 180离体细胞进行电脉冲作用 ,通过苔盼蓝追踪 ,发现在一定的条件下 ,随着对 S- 180离体细胞电穿孔的电压越大、电容越小、脉冲个数越多 ,其穿孔百分率越大。     

医学信息学的研究领域及人才培养

医学信息学(MedicalInformatics,又称医药信息学)是计算机科学、信息科学与医学科学结合,新近形成的前沿多学科交叉的科学,它以信息论、系统论、计算机科学技术为理论基础,几乎全方位地涉及所有的医药卫生领域,已成为现代和未来生物医学发展的基石。目前,医学信息学应用的领域,面临人才短缺的现象,本文论述了在生物医学工程学科中,建立医学信息本科专业方向,通过相关课程体系的设置,培养符合社会需要的医学信息人才。     

应用PCR-酶切法进行脊肌萎缩症基因诊断

目的探讨脊肌萎缩症(SMA)的基因诊断方法.方法基于运动神经元生存基因(SMN)的两个同源拷贝碱基上的差异,应用PCR-酶切分析法对10例临床和病理诊断为Ⅰ、Ⅱ、Ⅲ型SMA的患者及其直系亲属16人、25例正常对照进行SMN基因检测.结果 10例SMA患者中9例患者缺失SMN第7、8号外显子,1例患者仅缺失第7号外显子;正常对照组及患者亲属均未发现外显子缺失.结论 PCR-酶切检测SMN基因第7号、8号外显子缺失是诊断儿童型脊肌萎缩症可靠的基因诊断方法.