Metastable intermediates in the condensation of semiflexible polymers.

Motivated by results from an earlier Brownian dynamics simulation for the collapse of a single, stiff polymer in a poor solvent [B. Schnurr, F. C. MacKintosh, and D. R. M. Williams, Europhys. Lett. 51, 279 (2000)] we calculate the conformational energies of the intermediate (racquet) states suggested by the simulations. In the absence of thermal fluctuations (at zero temperature) the annealed shapes of these intermediates are well-defined in certain limits, with their major structural elements given by a particular case of Euler's elastica. In appropriate units, a diagram emerges that displays the relative stability of all states, tori, and racquets. We conclude that, in marked contrast to the collapse of flexible polymers, the condensation of semiflexible or stiff polymers generically proceeds via a cascade through metastable intermediates, the racquets, towards a ground state, the torus or ring, as seen in the dynamical simulations.

Structure activity studies on leaving group derivatives of [meso-1,2-bis-(2,6-dichloro-4-hydroxyphenyl)ethylenediamine] platinum(II).

The spatial structures of leaving group derivatives of [meso-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]platinum(II) (meso-1-PtL2; L2 = SO4, Cl2, I2, CBDC (cyclobutane-1,1-dicarboxylate)) were investigated by NMR methods and correlated with their reactivity against nucleophiles, their estrogenic potency, and their activity on the hormone dependent MCF-7 mammary carcinoma cell line. It was demonstrated that beside the non-leaving group meso-1 the PtL2 moiety of meso-PtL2 complexes is important for the estrogen receptor binding. Among the tested complexes meso-1-PtI2 possesses the highest affinity for the estrogen receptor (RBA = 2.6) and represents a strong estrogen on the MCF-7-2a cell line. The use of CBDC as leaving group decreases the effects. Meso-1-PtCBDC shows an RBA of 0.06 and has only half of the estrogenic activity. Both complexes are sufficiently stable under physiological conditions, so a transformation into the dichloroplatinum(II) complex prior to the binding to the estrogen receptor can be excluded. Due to their high stability meso-1-PtI2 and meso-1-PtCBDC were only marginally active on the human estrogen receptor positive MCF-7 cell line, while meso-1-PtSO4 and meso-1-PtCl2 reduced the cell growth to T/Cmax = 45% and 25%, respectively.

Stability and cellular studies of [rac-1,2-bis(4-fluorophenyl)-ethylenediamine][cyclobutane-1,1- dicarboxylato]platinum(II), a novel, highly active carboplatin derivative.

The synthesis of the diastereomeric [1,2-bis(4-fluorophenyl)ethylenediamine][cyclobutane-1, 1-dicarboxylato]platinum(II) complexes, rac- and meso-4F-Pt(CBDC), the evaluation of their structures, their tumor-inhibiting properties and their stability in physiological environment are described (reference complexes: the dichloro- and sulfatoplatinum(II) analogues, carboplatin and cisplatin). The most interesting diastereomer, rac-4F-Pt(CBDC), equals cisplatin and surpasses carboplatin in its effect on human breast cancer cell lines (MCF-7 and MDA-MB-231). Rac-4F-Pt(CBDC) is largely insensitive against attack of nucleophiles e.g. Cl-, a prerequisite for sufficient stability in vivo and for fewer side effects. In accordance with this, in vitro studies on the binding of rac-4F-Pt(CBDC) to albumin, the main plasma protein, show that the free, non-protein-bound fraction is relatively high, coming close to that of carboplatin. These properties are of importance for the transferability of the promising effects found in the cell culture experiments to in vivo conditions. The distinctly better anti-breast cancer activity of rac-4F-Pt(CBDC) than of carboplatin has been attributed to its ability to accumulate in the tumor cells. The human ovarian cancer cell line NIH-OVCAR-3 is also strongly inhibited by rac-4F-Pt(CBDC).

Expression of biologically active isoforms of the tumor angiogenesis factor VEGF in Escherichia coli.

Vascular endothelial growth factor (VEGF) was identified as an endothelial cell specific mitogen that induces angiogenesis and vascular permeability in vivo. VEGF is a homodimeric protein which contains three intramolecular and two intermolecular disulfide bridges. Here, we report on an efficient procedure for recombinant production of VEGF isoforms VEGF121 and VEGF165 in Escherichia coli. The proteins were solubilized from inclusion bodies, refolded, and purified by chromatographic methods. The final protein products were almost completely in the dimeric conformation, bound to VEGF receptor FLT1 with a Kd of 30 pM, stimulated proliferation of human umbilical vein endothelial cells half-maximally at a concentration of 30 pM, and induced in vivo neovascularization and vascular permeability on the chicken chorioallantoic membrane.

Arm function after axillary dissection for breast cancer: a pilot study to provide parameter estimates.

Sixty-three women participated in a study in Calgary, Alberta to assess the rate of arm recovery and factors affecting it up to one year after axillary node dissection for breast cancer. Outcomes included objective measures of swelling, mobility, and strength, and subjective assessments of pain (at rest and with movement) and stiffness. Approximately 42% of women had residual impairment of at least one type one year after surgery, the most common problems being pain (16%) and reduced grip strength (16%). Except for lymphedema, measurements one year after surgery showed little change from measurements at 6 months, suggesting that the shorter follow-up may be appropriate for assessing the long term effects of axillary dissection. Lymphedema was the only sequela which increased over time. The results provide parameter estimates for designing studies to evaluate the role of physiotherapy after axillary dissection.

Similarities and differences between cholinergic systems in the superior colliculus of guinea pig and rat.

We studied the distribution of acetylcholinesterase activity and choline acetyltransferase immunoreactivity in the superior colliculus of the guinea pig and the albino rat, using enzyme histochemical and immunohistochemical methods. Choline acetyltransferase-like immunoreactivity was localized in the neuropil throughout the colliculi, but the density of the immunoreactive neuropil varied among layers as well as between species. In the intermediate collicular layers the pattern of choline acetyltransferase immunoreactivity was closely matched by the distribution of acetylcholinesterase activity in guinea pig and rat, confirming our previous findings in the cat. Furthermore, in the guinea pig, but not in the rat, choline acetyltransferase-like immunoreactivity was localized in a prominent population of perikarya of the superficial gray layer.

Statewide dental auxiliary career mobility: an emerging reality for Kentucky.

The lack of articulation in allied health education has been identified as a significant barrier to career mobility. This paper describes an attempt to improve articulation of dental auxiliary training in Kentucky. Results included the development of a dental auxiliary core curriculum, an articulation model, and the successful negotiation of a systemwide transfer agreement. In addition, the project instilled a commitment on the part of the group members to continue working toward greater articulation for dental auxiliaries.