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.     

Drift hole mobility in strained and unstrained doped Si1-xGex alloys

Results of the drift hole mobility in strained and unstrained SiGe alloys are reported for Ge fractions varying from 0 to 30% and doping levels of 10¹⁵-10¹⁹ cm^-3. The mobilities are calculated taking into account acoustic, optical, alloy, and ionized-impurity scattering. The mobilities are then compared with experimental results for a boron doping concentration of 2×10¹⁹ cm^-3. Good agreement between experimental and theoretical values is obtained. The results show an increase in the mobility relative to that of silicon     

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.     

The effects of cholecystokinin A and B receptor antagonists, devazepide and L 365260, on citalopram-induced decrease of exploratory behaviour in rat

The present study has been divided into two sets. In the first set, the aim of the experiments was to investigate the dose-response effect of selective serotonin re-uptake inhibitor (SSRI) citalopram on rat exploratory behaviour in the elevated plus-maze. In the second set of experiments, the effect of cholecystokinin (CCK) CCKA and CCKB receptor antagonists, devazepide and L 365260, on citalopram-induced decrease of exploratory behaviour in the elevated plus-maze was studied. Citalopram (5 and 10 mg/kg) decreased the number of open and total arm entries, line crossings on open arms, and percentage of time spent exploring in open arm. Dose 15 mg/kg was without any effect on rat exploratory behaviour. Devazepide (0.01 and 1.0 mg/kg) failed to modify any of the citalopram-induced changes observed. L 365260 (1.0 mg/kg) reversed most of the effects of citalopram: the numbers of open and total arm entries, the number of line crossings, and the percentage of time spent exploring in open arms. L 365260 at dose level 0.01 mg/kg was ineffective. These results support the involvement of the CCKB receptor subtype in SSRI-induced anxiogenic-like effects in rodents.     

Capacity enhancement of cellular CDMA by traffic-based control ofspeech bit rate

Variable rate speech coding is now recognized as an important system component for high-capacity cellular networks because it exploits speech statistics to reduce the average bit rate, which results in reduced interference and increased capacity. Once a variable rate capability is available, an additional capacity enhancement can be achieved by introducing network control of the user bit rate in response to changing traffic levels. We introduce the concept of network control of rate and propose a particular network-control method for code-division multiple access (CDMA) systems. Based on an M/M/∞//M queueing model applied to a cell under heavy traffic conditions and a new performance measure called averaged speech quality, we obtain simulation results to demonstrate how network control of rate can achieve improved speech quality or increased capacity for a given quality objective     

Poly(A) metabolism in Xenopus laevis embryos: substrate-specific and default poly(A) nuclease activities are mediated by two distinct complexes

The metabolism of the poly(A) tail is a process important for the translational regulation of maternal mRNAs in Xenopus laevis oocytes and early embryos. Two poly(A) nuclease (PAN) activities have been described in Xenopus embryo or activated egg extracts (Legagneux et al (1995) RNA 1, 1001-1008). These activities (default PAN and EgPAN) are distinguishable by their deadenylation kinetics and their substrate specificities. In this report, we show that these activities display different sensitivities to biochemical treatments. Urea and, to a lesser extent, spermidine, inhibit EgPAN at concentrations which have no effect on default PAN. Heparin activates default PAN but inhibits EgPAN. When extracts are fractionated by ultracentrifugation, the default activity is recovered in one unique fraction, whereas two fractions must be combined to reconstitute the EgPAN activity. Moreover, these two deadenylation activities are separable by size exclusion chromatography under native conditions. We conclude that these two deadenylation activities are mediated by two protein complexes.     

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.     

Multispectral data compression using bidirectional interbandprediction

The introduction of high spatial and spectral resolution sensors on-board remote-sensing spacecraft has increased, by orders of magnitude, the data rates which need to be sustained on the down-link or cross-link transmission channels. Since these channels are severely limited in capacity, the need arises to perform on-board compression to reduce the volume of data which would need to be down-linked. This paper discusses the development and refinement of a low complexity lossy spectral/spatial compression method which provides high compression ratios at low levels of distortion. The developed techniques uses pixels in adjacent bands to predict the intensity of pixels in the band being compressed via a simple linear prediction model. This prediction method when combined with a low-distortion discrete cosine transform (DCT) block coding method yields performance comparable to block-adaptive Karhunen-Loeve Transform (KLT)-DCT methods without incurring the complexity penalty of the KLT. The methods' performance suffers under misregistration. A fractional-pixel interpolation enhancement to the basic technique significantly improves the performance in the case of misregistered bands