Cytotoxic and antitumor activity of a recombinant tumor necrosis factor-B1(Fv) fusion protein on LeY antigen-expressing human cancer cells

We have constructed a fusion protein composed of tumor necrosis factor alpha (TNF-alpha) fused at its COOH terminus to the scFv region of monoclonal antibody (mAb) B1, an antibody that recognizes LeY antigen present on many human cancer cells. Our rationale for fusing the scFv to the COOH terminus of TNF was to diminish the binding of the fusion protein to TNF receptors because the COOH terminus of TNF is involved in binding, and thus to partially inactivate (detoxify) the molecule. The Fv region should then target and accumulate the fusion protein on cancer cells, which should compensate for the reduced binding affinity of the TNF moiety and lead to selective killing of TNF-sensitive antigen-expressing cancer cells. The fusion protein was expressed in Escherichia coli and found in insoluble inclusion bodies. After refolding and purification by anion exchange, Ni-NTA affinity, and size-exclusion chromatography, we obtained monomeric TNF-B1(Fv). This molecule binds to LeY antigen on cancer cells with the same affinity as B1(scFv) and B1(scFv) immunotoxins but with significantly lower affinity to the TNF receptor compared to the TNF trimer. TNF-B1(Fv) is very toxic to LeY antigen-expressing cancer cells that are sensitive to TNF (e.g., MCF-7 breast or CRL-1739 gastric cancer cells). This cytotoxicity is antibody targeted and TNF mediated because it can be prevented (as shown on MCF-7 cells) by an antibody competing for LeY antigen binding and by an antibody that neutralizes TNF-alpha. TNF-B1(Fv) kills TNF-alpha-sensitive cells that do not express the target antigen only at much higher doses than TNF trimer, and it does not kill LeY-bearing but TNF-alpha-resistant cells. TNF-B1(Fv) can cause significant tumor regression of MCF-7 tumor xenografts in mice at doses that are not toxic to the mice. Thus, the reduced binding of the TNF moiety to TNF receptors, combined with binding of the B1(Fv) portion to LeY antigen, makes TNF-B1(Fv) an agent for selective killing of LeY-expressing TNF-sensitive cancer cells.     

Cortical gray matter volume deficits in schizophrenia: a replication

We sought to replicate an earlier finding of widespread deficit in cortical gray matter in schizophrenia by testing new samples of 22 schizophrenic patients and 27 controls between the ages of 21-46 years. Brain values for both patients and controls were standardized against age and head size norms derived from a larger control group (n = 73) spanning a wider age range (21-70). Compared to the new age-matched controls, the new schizophrenic sample showed a deficit in gray matter volume affecting the cortex as a whole and enlargement of the lateral and third ventricles. Thus, widespread cortical gray matter deficit is a replicable feature of the brain dysmorphology of schizophrenia in young to middle-aged men.     

关于解决供电配电所问题的协调控制战略研究

提出了在主变压器事故、工作计划、过负荷、预防过负荷等问题在供电配电所出现的时候,以电力SCADA系统和配电SCADA的协作控制战略(CCT:Coord ination Control Strategy)为基础,研究运用负荷切换战略来消除事故波及效果的同时提高配电所运营安全性的方法.协调控制战略分为2阶段:第1阶段,通过利用母线重构解决方案(DSBRES:D istribution Substation Bus ReconfigurationExpert System)得出供电配电所的母线重构战略;第2阶段,根据从第1阶段得出的资料和配电系统重构解决方案(DSFRES:D istribution Systsem FeederReconfiguration Expert System)而得出配电系统线路重构.最后,给出了能表示供电、配电所和配电系统特性的代表性供电配电所模式和配电系统的模式.     

Low frequency dynamic viscoelastic properties of human mitral valve tissue

Trypsin incubation was performed on split-skin grafts from rats, pigs, and humans. The separation of dermis and epidermis was best achieved when incubating in 0.5% crude trypsin in Hank's balanced salt solution. Separation occurred at 37 degrees C in 1 1/2 hours for all species. At 4 degrees C, the separation took 2 1/2 hours for pigskin, 3 1/2 to 4 1/2 hours for human skin, and 5 to 6 hours for rat skin. Histological examination showed a cleaner separation of both rat skin and pigskin was obtained at 4 degrees C than at 37 degrees C. Large areas of skin (1600 mm2) could be separated easily as long as adequate amounts of solution were used.