A radioimmunologic technique to screen for antibodies to alpha-2 interferon

A radioimmunologic technique has been developed to screen sera of persons receiving human alpha-2 interferon for the presence of specific antibodies to alpha-2 interferon. The method is sensitive and easy to perform. It tests the ability of the sera to neutralize alpha-2 interferon and prevent the interferon from being detected by an immunoradiometric assay. The results obtained using this technique are in good agreement with an anti-viral, cytopathic effect assay. Using the immunological technique, the sera from more than 1000 individuals who had received different doses of alpha-2 interferon by one or more of various routes of administration were tested. Twenty-five sera representing 14 individuals gave a positive or possibly positive reaction in the assay. Three of the 14 individuals were positive prior to receipt of alpha-2 interferon. Another 3 had reverted to negative when tested a few months later. Of the remaining 8, only 4 developed titers greater than 100 neutralizing units/ml. Hence approximately 1% of the alpha-2 interferon recipients may have produced neutralizing antibodies.     

柠檬提取物对新城疫及柯萨奇病毒作用的实验研究

目的:测试并比较柠檬提取物0#及3#在不同的实验方法下对新城疫病毒和柯萨奇病毒B3的杀灭作用。方法:直接杀灭作用:将新城疫病毒和柯萨奇病毒B3分别与柠檬提取物0#和3#体外作用1h,然后加入到培养好的Vero细胞中,培养72h。预防作用:将不同浓度的柠檬提取物0#和3#分别加入培养好的Vero细胞中作用24h,然后分别加入新城疫病毒和柯萨奇病毒B3与柠檬提取物0#和3#的混合液,培养72h。治疗作用:将新城疫病毒和柯萨奇病毒B3分别加入培养好的Vero中,作用1h,然后分别加入0#及3#药品,培养72h。3种方法与未加柠檬提取物的病毒液对细胞的作用相比较,通过CPE法观察药品对病毒的作用。结果:在柠檬提取物0#对新城疫病毒的直接杀灭作用中,实验组较对照组有显著性差异(P<0.05);在柠檬提取物3#对柯萨奇病毒B3的预防作用中,实验组较对照组有显著性差异(P<0.05);在柠檬提取物0#及3#对新城疫病毒和柯萨奇病毒B3的治疗作用中,实验组较对照组无显著性差异(P>0.05)。结论:柠檬提取物0#对新城疫病毒具有杀灭作用;柠檬提取物3#对柯萨奇病毒具有预防作用;0#及3#对新城疫病毒和柯萨奇病毒B3均无治疗作用。     

Determination of sibship by PCR-amplified short tandem repeat analysis in Taiwan

BACKGROUND: Sibship determination for any two persons whose parents have died is one of the most fundamental issues of personal identification, second only to those of a parent-child relationship. STUDY DESIGN AND METHODS: By automated fluorescence analysis of a PCR-amplified short tandem repeat (STR) system in conjunction with capillary electrophoresis, a panel of up to 15 polymorphic, autosomal, unlinked STR loci was used to investigate sibship index (SI) values in a cohort of 126 true sibling pairs. These SI values were then compared with those of 126 random pairs. RESULTS: The 15-loci STR panel provides a cumulative power of exclusion of 0. 9999997. Of the 126 random pairs, 124 (98.4%) had cumulative sibship indices (CSIs) of <1.0, and none had a CSI of >3.0 (median, 0.0101; range, 0.0000003-2.5376). In contrast, 107 (85%) of the 126 sibling pairs had a CSI of >100 (median, 5,579.9853; range, 0.0747-9,406,829, 249.8461). However, five pairs (4%) of the sibling group had a CSI of <3.0. True sibship was confirmed for this particular group by additional paternity testing and mitochondrial DNA sequence analysis. Among a total of 1890 observations (15 loci x 126 pairs), two alleles per locus were shared 760 times (40.21%) (mean, 6.03 loci; range, 1-10) in the sibling group, but only 192 times (10.16%) in the random group (mean, 1.52 loci; range, 1-5) (p<0.001). No alleles were shared 696 times (36.83%) in the unrelated pairs, as compared to 176 times (9.31%) in the sibling group (p<0.001). A polarized distribution was not noted in the sharing of single alleles in either the random or the sibling group: 1002 observations (53.02%) and 954 observations (50.48%), respectively. CONCLUSION: Highly polymorphic STR analysis can be discriminative in most sibship determinations, and the sharing of two alleles per locus is most informative in indicating sibship. Complementary mitochondrial DNA sequence analysis is mandatory in a few cases to exclude or establish true sibship when CSIs are equivocal and neither parent is available.     

溶瘤病毒dl1520体外对肝癌细胞杀伤作用的研究

目的:探讨E1B缺陷溶瘤腺病毒dl1520体外对肝癌细胞Hep3B的杀伤作用。方法:通过细胞病变效应(CPE)观察d l1520对肝癌细胞株的杀伤作用;MTT法测定对肝癌细胞生长抑制作用,并通过空斑法测定病毒增殖,探讨其杀伤机理。结果:d l1520在肝癌细胞株Hep3B中可复制增殖并导致明显细胞病变效应,显著抑制癌细胞的生长。结论:d l1520体外可在肝癌细胞Hep3B中复制并裂解杀伤肿瘤细胞。     

羧基肽酶E (CPE)在人乳腺腺癌中的表达和功能

 【摘要】目的 观察乳腺腺癌中羧基肽酶E(carboxypeptidase E,CPE)介导的神经内分泌肽加工和表达。方法 使用RT PCR、免疫组化、ELISA和Western blot等方法,比较CPE和生长激素释放激素(growth hormone releasing hormone,GHRH)基因和蛋白质水平在42例乳腺癌和21例癌旁正常组织中的表达。结果 乳腺癌组织中的CPE基因表达水平为1 024±237,而癌旁正常组织中CPE基因表达水平为805±83 (P<0.01)。与乳腺癌旁正常组织比较,癌组织中CPE蛋白质显示了较高的表达 (P<0.01)。乳腺癌组织中的GHRH基因表达水平为1 522±457,而癌旁正常组织中为1 067±437,差异有统计学意义(P<0.01)。与乳腺癌旁正常组织比较,癌组织中GHRH蛋白表达被上调 (P<0.01)。结论 癌组织中CPE和GHRH高表达提示癌细胞中存在较强的由CPE酶介导的神经内分肽转录后加工能力。     

Isolation, identification and antiviral activities of metabolites of calycosin-7-O-β-D-glucopyranoside

In vivo and in vitro metabolites of calycosin-7-O-β-d-glucopyranoside in rats were identified using a specific and sensitive high performance liquid chromatography-tandem mass spectrometry (HPLC-MSⁿ) method. The parent compound and twelve metabolites were found in rat urine after oral administration of calycosin-7-O-β-d-glucopyranoside. The parent compound and six metabolites were detected in rat plasma. In heart, liver, spleen, lung and kidney samples, respectively, six, eight, seven, nine and nine metabolites were identified, in addition to the parent compound. Three metabolites, but no trace of parent drug, were found in the rat intestinal flora incubation mixture and feces, which demonstrated cleavage of the glycosidic bond of the parent compound in intestines. The main phase I metabolic pathways of calycosin-7-O-β-d-glucopyranoside in rats were deglycosylation, dehydroxylation and demethylation reactions; phase II metabolism included sulfation, methylation, glucuronidation and glycosylation (probably). Furthermore, two metabolites commonly found in rat urine, plasma and tissues were isolated from feces and characterized by NMR. The antiviral activities of the metabolite calycosin against coxsackie virus B₃ (CVB₃) and human immunodeficiency virus (HIV) were remarkably stronger than those of calycosin-7-O-β-d-glucopyranoside.     

Anti-tumor efficacy and pre-clinical immunogenicity of IFNα2a-NGR

Previously studies have shown that tumor-homing peptide NGR enhances the therapeutic efficacy of human interferon α2a (IFNα2a) against tumors. Here we investigated in vivo anti-tumor effect of recombinant human IFNα2a-NGR (rhIFNα2a-NGR) against human lung adenocarcinoma cell line SPC-A-1, A549 and murine Lewis lung carcinoma (LLC) subcutaneously xenografted tumors and further assessed the immunogenicity of rhIFNα2a-NGR in Sprague Dawley (SD) rats and rhesus monkeys. We found that rhIFNα2a-NGR significantly inhibited the growth of SPC-A-1, A549 and LLC cells-xenografted tumors in a dose-dependent manner. Although the antibodies to rhIFNα were detected in the serum of SD rats and rhesus monkeys treated with rhIFNα2a-NGR, these antibodies did not cause obvious pathological consequence. Taken together, these data demonstrate that rhIFNα2a-NGR has obvious anti-tumor efficacy in vivo, perhaps due to the tumor-homing peptide NGR. Thus rhIFNα2a-NGR represents a promising novel drug for effective treatment of cancer.     

Deregulated mTOR-mediated translation in intellectual disability

Local translation of dendritic mRNAs is a key aspect of dendrite and spine morphogenesis and synaptic plasticity, two phenomena generally compromised in intellectual disability disorders. Mammalian target of rapamycin (mTOR) is a protein kinase involved in a plethora of functions including dendritogenesis, plasticity and the regulation of local translation. Hence, this kinase may well be implicated in intellectual disability. Hyperactivation of mTOR has been recently reported in mouse models of Fragile X and tuberous sclerosis, two important causes of intellectual disability. Moreover, local dendritic translation seems to be increased in Fragile X syndrome. Recent findings show that the mTOR pathway is also deregulated in murine models of Rett's syndrome and Down's syndrome. As in Fragile X, local dendritic translation seems to be abnormally active in Down's syndrome mice, while rapamycin, a Food and Drug Administration-approved mTOR inhibitor, restores normal rates of translation. Rapamycin administration in tuberous sclerosis mice rescues deficits in behavior and synaptic plasticity. Indeed, mTOR-dependent deregulation of local translation may be a common trait in different intellectual deficiencies, suggesting that mTOR inhibitors may have significant therapeutic potential for the treatment of diverse forms of cognitive impairment.