Polymeric prodrugs of mitomycin C designed for tumour tropism and sustained activation

Prodrugs of mitomycin C (MMC) based on soluble poly-[N-(2-hydroxyethyl)-L-glutamine] (pHEG) polymers have been evaluated as tumour-targeted drugs. These materials are designed to exploit the enhanced permeability of tumour vasculature, combining a passive tumour tropism with decreased systemic liberation of free MMC. A tri- or tetrapeptide linkage (e.g. Gly-Phe-Ala-Leu) between pHEG and the aziridine nitrogen of MMC can combine good hydrolytic stability with rapid cleavage by lysosomal enzymes, releasing free MMC. The conjugates showed decreased systemic toxicity and could be administered to mice at a total MMC dose of 15 mg/kg i.v., compared with just 6 mg/kg for free MMC. Conjugates also showed better activity against animal models of established tumours, achieving up to 77% increased life span (ILS) against solid P388 leukaemia, compared with only 23% for free MMC, and up to 121% ILS against solid C26 colorectal carcinoma, compared with no activity for the free drug. Improving the therapeutic index of anticancer drugs by combining tumour tropism with decreased systemic toxicity is a versatile approach that should produce a new generation of improved anticancer agents.     

Effect of postoperative mydriatics on the iris

PURPOSE: To assess the role postoperative mydriatics play after extracapsular cataract extraction (ECCE) and posterior chamber intraocular lens (IOL) implantation in causing iris modifications and in controlling inflammation. SETTING: Outpatients Department, Ninewells Hospital, Dundee, Scotland. METHODS: The prospective study comprised 136 patients who had standardized ECCE. Half the patients used a mydriatic for 2 weeks postoperatively. Anterior chamber activity, pain, and eye redness were evaluated at 2 weeks postoperatively; pupil shape, peripheral anterior synechias, IOL position, and iris adhesions, at 6 weeks. RESULTS: Iris-lens adhesions were significantly more common in the group using a mydriatic. There was no difference between the two groups in postoperative inflammation. CONCLUSION: Mydriatics should not be used routinely after ECCE with posterior chamber IOL implantation.     

Control of stroma-dependent hematopoiesis by basic fibroblast growth factor: stromal phenotypic plasticity and modified myelopoietic functions

The immunological agglutination reactions of physically absorbed F(ab')2 molecules onto anionic and cationic latex particles have been investigated by means of optical absorbance measurements. These measurements have been conducted under different conditions to determine the most influential factors. Surface F(ab')2 and BSA densities, particle concentration in the reaction medium and polyethylene glycol concentration are some of these factors. Sensitized cationic and anionic latexes differ considerably with respect to their colloidal stability and reactivity. As a general rule, the sensitized cationic latex has a relatively higher colloidal stability and hence, it provides reagents with a better optical response. Less than 0.025 microgram/ml of C-reactive protein has been detected using this particle enhanced optical immunoassay.     

Increasing the service properties of weld joints by electrohydroimpulse treatment

Known examples of the positive influence of electrohydroimpulse treatment on the quality of weld joints of various steels, particularly including an increase in their long-term and cyclic strength and also corrosion resistance, are analyzed. It is shown that in this case there is a reduction in residual macro- and micro-stresses and also a change in the parameters of the dislocation structure of the joint metal in the direction of stabilization of it.Translated from Problemy Prochnosti, No. 4, pp. 119–123, April, 1996.     

The electrostatic problem for the SAW interdigital transducers inan external electric field. II. Periodic structures

For pt.I see ibid., vol.43, no.6, pp.1150-9 (1996). An exact solution of the electrostatic problem for calculating the surface charge and electric field distributions in an arbitrary periodic interdigital transducer (IDT) is given using the results of our companion paper. An arbitrary external electric field may be specified along the electrode structure with the unit cell containing one electrode, or several electrodes, of different widths. The potentials of the electrodes that may be specified are also arbitrary. It is shown that in the case without an external field, the solution includes all the known results as special cases. The case of shorted electrodes in the external electric field is investigated in detail. The surface charge and electric field distributions are calculated for a spatially harmonic external field with an arbitrary wavenumber. The results of the calculations are represented graphically for various ratios between the period of the electrode structure and the wavelength of the external field for the case of a unit cell containing one or two electrodes of different widths     

Thermal expansion of semiconductor materials

The thermal expansion of tellurides of germanium, bismuth, and intermetallic compounds is investigated over the temperature range 293-973 K.Belarusian Agricultural Technical University, Minsk. Translated from Inzhenerno-Fizicheskii Zhurnal, Vol. 66, No. 5, pp. 612–616, May 1994.     

Mental health and support of women treated for breast cancer

This article presents the results of a pilot-study conducted on a small sample of women with breast cancer and the members of their social support system. The purpose was to determine the potential link between the mental health of the breast cancer patient and their support system. Mental health was assessed with the SCL-90-R (Derogatis, 1977), a self-report scale composed of 90 items divided into nine categories, offering three global indicators of distress: the Global Severity Index (GSI); the Positive Symptom Distress Index (PSDI), and the Positive Symptom Total (PST). The SCL-90-R was distributed to a sample of 14 subjects: seven women treated for breast cancer and seven significant others (social support). The results led to the definition of symptoms such as hostility, phobic anxiety and psychosis specific to either the woman or the support system.     

Identification of in vitro phosphorylation sites in the growth cone protein SCG10. Effect Of phosphorylation site mutants on microtubule-destabilizing activity

SCG10 is a neuron-specific, membrane-associated protein that is highly concentrated in growth cones of developing neurons. Previous studies have suggested that it is a regulator of microtubule dynamics and that it may influence microtubule polymerization in growth cones. Here, we demonstrate that in vivo, SCG10 exists in both phosphorylated and unphosphorylated forms. By two-dimensional gel electrophoresis, two phosphoisoforms were detected in neonatal rat brain. Using in vitro phosphorylated recombinant protein, four phosphorylation sites were identified in the SCG10 sequence. Ser-50 and Ser-97 were the target sites for protein kinase A, Ser-62 and Ser-73 for mitogen-activated protein kinase and Ser-73 for cyclin-dependent kinase. We also show that overexpression of SCG10 induces a disruption of the microtubule network in COS-7 cells. By expressing different phosphorylation site mutants, we have dissected the roles of the individual phosphorylation sites in regulating its microtubule-destabilizing activity. We show that nonphosphorylatable mutants have increased activity, whereas mutants in which phosphorylation is mimicked by serine-to-aspartate substitutions have decreased activity. These data suggest that the microtubule-destabilizing activity of SCG10 is regulated by phosphorylation, and that SCG10 may link signal transduction of growth or guidance cues involving serine/threonine protein kinases to alterations of microtubule dynamics in the growth cone.     

On the Possibility of Observing Third Sound on 3He

This paper focuses on the hydrodynamics of third sound on a superfluid ³ He film. We solve the hydrodynamical equations in the limit of thick films with weak interaction with the substrate. The surface tension at the free interface is shown to have a large effect on the third sound velocity and on the attenuation for frequencies larger than 1Hz. In the case of a diffusely scattering substrate a ripplon-like dispersion relation is found for this frequency range.