Anti-IgM induces transforming growth factor-beta sensitivity in a human B-lymphoma cell line: inhibition of growth is associated with a downregulation of mutant p53

We wished to examine the role of transforming growth factor-beta (TGF- beta) in the regulation of human lymphoma cell growth. The RL cell line is an immunoglobulin M (IgM)+, IgD+ B lymphoma cell line, which does not constitutively express receptors for TGF-beta, and thus has lost the ability to respond to the inhibitory effects of TGF-beta. We demonstrate here that anti-Ig antibodies can efficiently upregulate the expression of TGF-beta receptors and promote sensitivity to growth inhibition by TGF-beta. Furthermore, because TGF-beta has been shown to function in late G1 of the cell cycle, we examined the ability of TGF- beta to modulate two tumor suppressor proteins known to be critical regulators of the G1/S transition, Rb and p53. Rb is a 105- to 110-kD phosphoprotein, which has been shown to maintain its growth suppressive function when it is found in the hypophosphorylated state. Wild-type p53 is a 53-kD phosphoprotein that appears to be important in preventing cell-cycle progression and promoting apoptosis in cells with DNA damage, whereas mutant p53 can overcome those functions. We show here that TGF-beta treatment of phorbol myristate acetate (PMA) or anti- Ig-activated RL cells results in growth inhibition through a dual effect on Rb and mutant p53. After TGF-beta treatment, we observe a predominance of Rb in the hypophosphorylated, growth suppressive form. In addition, we show a decrease in levels of mRNA and protein for mutant p53. We also show that, although these changes are sufficient to halt progression through the cell cycle, the cells do not appear to undergo extensive programmed cell death following 72 hours of TGF-beta treatment. Thus, although these lymphoma cells maintain the capacity to be negatively growth regulated by TGF-beta, the ability of TGF-beta to induce apoptosis must be independently controlled.     

Selective delivery of chemotherapeutic agents with a new catheter system

A new catheter system was used in ten patients (16 infusions) for infusion of chemotherapeutic agents to the sites of malignant gliomas. Thirteen infusions to the supraophthalmic region were successful, as were three infusions to the posterior cerebral region. There were no complications after the infusions. A neurologic complication occurred in one patient in whom two successful supraophthalmic infusions were previously carried out. In this patient the guide wire separated during catheter placement into the posterior cerebral artery.     

Altered functional responsiveness of thymocyte subsets from CD3delta- deficient mice to TCR-CD3 engagement

CD3delta-deficient (delta degrees) mice are defective in alphabeta T cell development. Here we explore the capacity of TCR-CD3 signaling complexes expressed on delta degrees thymocytes to mediate the following functional outcomes in response to antibody cross-linking: (i) the transition from the CD4-CD8- to CD4+CD8+ stage, (ii) the transition from the CD4+CD8+ to CD4+CD8- or CD4-CD8+ stages and (iii) the induction of apoptosis. We provide evidence that CD3deltaepsilon complexes are dispensable for mediating the anti-CD3-mediated CD4-CD8- to CD4+CD8+ transition. On the other hand, CD3delta is critical at the CD4+CD8+ stage. We demonstrate that CD4+CD8+ thymocytes from delta degrees mice, unlike delta degrees CD4-CD8- thymocytes and wild-type CD4+CD8+ thymocytes, require prolonged or consecutive stimuli to elicit functional responses. Depending on the nature of the secondary stimulus, delta degrees thymocytes can be induced to undergo apoptosis or preferential maturation to the CD4-CD8+ stage. Taken together these results indicate that the signaling capacity of the TCR-CD3 complex is noticeably altered in the absence of CD3delta. The essential role of CD3delta at the CD4+CD8+ stage of development correlates with the onset of TCRalpha rearrangement, consistent with a critical structural and/or functional relationship between CD3delta and TCRalpha.      

石杉碱甲类似物的研究Ⅲ．N－甲基吡啶酮石杉碱甲类似物的合成

石杉碱甲（１）是从中草药石杉属植物千层塔（ＬｙｃｏｐｏｄｉｕｍｓｅｒｒａｔｕｍＴｈｕｎｂ．）中分得的一种高效可逆的乙酰胆碱酯酶抑制剂，临床试验证实它对早老性痴呆症有显著疗效。本文报道Ｎ－甲基吡啶酮石杉碱甲类似物２和３的合成。２－甲氧基－５－甲氧羰基－１１－亚甲基－５，９－甲撑环辛－７－烯并吡啶（９）在乙腈中用三甲基氯硅烷和碘化钠选择性脱保护以定量的产率得吡啶酮１０，再用甲醇钠和碘甲烷甲基化得Ｎ－甲基吡啶酮１１，１１经碱性水解，Ｃｕｒｔｉｕｓ重排和氨基的脱保护得Ｎ－甲基吡啶酮石杉碱甲类似物２。通过类似的途径从中间体２－甲氧基－５－甲氧羰基－７－甲基－１１－酮－５，９－甲撑环辛－７－烯并吡啶（１４）合成了类似物３。类似物２和３的乙酰胆碱酯酶抑制活性均低于天然石杉碱甲。     

Mounting and calibration of stairs on piezoelectric force platforms

To calculate the centre of pressure using piezoelectric force plates mounted on pads, no net tensile stresses may be imposed on the surface of the plate. This condition is violated when stairs are attached to the plates, unless the plates are preloaded. Typical shear forces encountered when climbing stairs were used to determine required preloads of approximately 16.4 N/cm step height. Vertical and horizontal loads were applied at known locations on the steps, and points of application were calculated. Deviations were within ± 3 mm. The effect of point of application inaccuracy on calculated joint moments is considerable. A 2 cm medial shift in the point of application resulted in calculated peak knee abduction/adduction moment errors of 35%.