酸果可促进卵巢癌治疗

一个新的研究提出,喝下一杯酸果汁将大大地推进卵巢癌病人对化学疗法的敏感性。研究人员说,在实验室实验中,用果汁来预处理卵巢癌细胞将把药物的杀伤力骤然提升6倍。研究员强调这个发现还是实验结果也只是初步结果,但它给已经开始抵抗治疗的卵巢肿瘤病人提供了一种新选择。     

Rescue of SV 40 from interferon-treated heterokaryons

Summary Simian virus 40 (SV 40)-transformed nonpermissive cells express only the early products of SV 40. Heterokaryons formed by fusion of these transformed cells with uninfected permissive cells support the activation of the resident viral genome leading to subsequent viral DNA replication, late protein synthesis and release of progeny virus. Pretreatment of heterokaryon cultures with either mouse or monkey interferon (IFN) before fusion with polyethylene glycol (PEG) produced a dose-dependent inhibition in the appearance of free viral DNA as well as production of infectious virus. The decreased yield of SV 40 in these cultures was similar to the inhibition which was observed in mouse or monkey cells incubated with homologous IFN prior to exogenous infection with SV 40. when IFN was added to the cultures at progressively later times after fusion with PEG, there was less inhibition of virus production. Although there was a comparable decrease in the production of virus by pretreatment with either mouse or monkey IFN, monkey IFN exerted the inhibition for a longer period of time when added after heterokaryon formation. These results demonstrate that IFN treatment applied even after initiation of SV 40 replication can still inhibit virus multiplication.With 1 Figure     

The mechanism of stimulation of the antiviral factor (AVF) in Nicotiana leaves. The involvement of phosphorylation and the role of the N-gene.

Crude preparations of a precursor of the antiviral factor (pre-AVF) were made from noninfected Nicotiana leaves, either carrying the N-gene or from which the N-gene is absent. These pre-AVF preparations could be activated to give antiviral activity. Crude enzyme preparations, made only from N-gene-carrying plants, but regardless of TMV-infection, served as activating systems. This activation requires ATP, CAMP and cGMP and is associated with the appearance of a new phosphor ylated material seen by polyactylamide gel electrophoresis. The induced antiviral activity has been purified as AVF but was separated from the phosphorylated material. It is proposed that an activating system, determined by the N-gene, is itself being activated through phosphorylation following TMV infection and processes a “pre-AVF” to make active AVE.     

Analysis of antigen specific T cell helper function in first degree relatives of patients with systemic lupus erythematosus (SLE).

Fourteen families with first degree relatives of patients with systemic lupus erythematosus (SLE) were studied for the ability of their members to respond to the synthetic polypeptide antigen (T,G)-A-L. The family members were also tested for their HLA determinants. All SLE patients tested responded to (T,G)-A-L as measured by the production of (T,G)-A-L specific T cell helper factors by their antigen activated T cells, confirming our previous findings that 100% of SLE donors responded to (T,G)-A-L in contrast to 50% responders in a control population of healthy donors. The general defect in the regulation of immune responses in SLE patients was further indicated by the demonstration that an SLE patient who is a daughter of non-responder parents to (T,G)-A-L, responded to this genetically regulated antigen. In contrast to our observations with SLE patients, the genetic regulation of the ability to respond to (T,G)-A-L was shown not to be impaired in healthy first degree family members of SLE patients and the segregation of the immune response potential in these families was as expected from an inherited dominant trait.     

Monoclonal anti-la antibody derived from a mouse with experimental SLE is similar to human anti-la antibodies

The La antigen is a highly conserved protein, originally defined by sera of patients with Sj?gren's syndrome or systemic lupus erythematosus (SLE). In the present study, we have produced and characterized a monoclonal anti-la antibody derived from mice with experimental SLE. The induction of SLE in these mice was achieved by their immunization with a murine monoclonal anti-idiotypic antibody against a common idiotype (16/6 Id) found in SLE patients. The monoclonal anti-La antibody derived from these mice was found to be virtually identical to the anti-La antibodies found in human autoimmune sera. First, its binding to different nuclear extracts, as well as to protease-digested HeLa nuclear protein extracts, was found to be identical to that of human anti-La antibodies. Second, an inhibition study on blotted proteins demonstrated a very close relationship between the epitopes recognized by the murine monoclonal anti-La antibody and the human anti-La serum. Third, the monoclonal anti-La antibody was found by immunofluorescence to be directed against a nuclear antigen that gave a speckled pattern. Finally, the monoclonal anti-La antibody immunoprecipitated the La-associated small RNAs. This report provides evidence for the similarity of murine anti-La antibody produced in experimental SLE and human anti-La antibodies formed in autoimmunity.     

Liposomes as immunological adjuvants in eliciting antibodies specific to the synthetic polypeptide poly(LTyr,LGlu)-poly(DLAla)–poly(LLys) with high frequency of site-associated idiotypic determinants

The antibody response to the synthetic polypeptide, poly(LTyr, LGlu)-poly(DLAla)–poly(LLys), [(T, G)-A–L], injected entrapped in liposomes which served as adjuvant, has been analyzed. The liposomes used were composed of phosphatidylcholine, cholesterol, dicetylphosphate and DL α-tocopherol (molar ratios as 4:3:0.1:0.5) and therefore, were negatively charged. Since the (T, G)-A–L is also negatively charged, no free complexes were formed. The (T, G)-A–L was found to be entrapped inside the enclosed volume of the liposomes, and no (T, G)-A–L antigenic determinants could be detected on the liposomal membranes. Injection of high-responder C3H.SW (H-2^b) mice with (T, G)-A–L-bearing liposomes demonstrated that the i.p. and the i.v. routes of immunization were efficient in eliciting (T, G)-A–L-specific antibodies, whereas the i.d. injection led to poor antibody responses. The latter route of immunization is the most effective when (T, G)-A–L is injected in complete Freund's adjuvant (CFA). When low doses (0.1 and 1 μg) of (T, G)-A–L were used for immunization, the liposomes were better adjuvants than CFA. The effectiveness of the liposomes as immunological adjuvants was also shown in their ability to induce high-potential, primed memory cells. The pattern of low (H-2^{k, a}) and high (H-2^b) responsiveness to (T, G)-A–L was retained following immunization with (T, G)-A–L entrapped in liposomes, as tested in two pairs of congenic strains. (T, G)-A–L-specific antibodies induced by injection with 1μ antigen entrapped in liposomes bear the (T, G)-A–L site-related idiotypic markers of C3H.SW (Igh-1^a) mice in a significantly higher frequency than the homologous idiotypes, namely the antibodies elicited in this strain against (T, G)-A–L in CFA. Thus, liposomes may serve as adjuvants for the production of relatively restricted (T, G)-A–L-specific antibodies of high qualitiy.     

Genetically regulated human (T,G)-AL specific helper T cell replacing factors possess HLA-DR and Vh determinants

Human (T,G)-AL specific T cell helper factors secreted by in vitro activated peripheral blood lymphocytes of normal donors were characterized. Factors were passed through columns of Sepharose coupled either to antibodies against human immunoglobulin or antibodies against the variable region of the heavy (V_h) and light (V_l) chains of human immunoglobulin. In addition, the same factors were applied to columns of Sepharose coupled to anti-HLA-DR antibodies or to monoclonal antibodies against human Ia or β₂-microglobulin. The activity of the antigen specific factors was removed by the anti-V_h antibodies and not by anti-V_l or anti-human immunoglobulin antibodies. The factors passed through Sepharose coupled to anti-DR antibodies could be removed and eluted from columns of anti-DR antibodies relevant to the donors' DR antigens. The same factors were also removed by a monoclonal antibody (anti-Ia) which recognizes a monomorphic determinant on HLA-DR, but not by monoclonal anti-β₂-microglobulin. The results suggest that the genetically regulated (T,G)-AL specific helper factors possess HLA-DR as well as V_h determinants in their active moiety.     

Characterization and role in experimental systemic lupus erythematosus of T-cell lines specific to peptides based on complementarity-determining region-1 and complementarity-determining region-3 of a pathogenic anti-DNA monoclonal antibody

Peptides based on the complementarity-determining region 1 (CDR1) and CDR3 of an anti-DNA monoclonal antibody (mAb) carrying the 16/6 idiotype (Id) were shown to induce experimental systemic lupus erythematosus (SLE) in susceptible mouse strains. In the present study, T-cell lines specific to the pCDR1 and pCDR3 peptides were established in BALB/c and in SJL mice, respectively. The T-cell lines were characterized and analysed for their pathogenicity upon administration to syngeneic mouse strains. Both T-cell lines expressed the alphabeta T-cell receptor (TCR) and the CD4+ CD8- phenotype. Additionally, both cell lines secreted interleukin (IL)-4 and IL-10 upon stimulation with their specific peptide, thus belonged to the T helper 2 (Th2) subset. Upon immunization, the pCDR3-specific T-cell line induced experimental SLE in SJL mice. The animals produced high levels of autoimmune anti-DNA and antinuclear protein antibodies, as well as anti-16/6 Id antibodies (Abs). Furthermore, the mice developed clinical manifestations, including leukopenia, proteinuria and accumulation of immune complex deposits in their kidneys. The pCDR1-specific T-cell line failed to induce SLE when injected into BALB/c mice. It is thus suggested that pCDR3 is an immunodominant epitope in experimental SLE and that pCDR3-specific T cells initiate autoimmunity, leading to SLE, probably via epitope spreading.