Reflections on simultaneous radio-polychemotherapy in head-neck carcinomas]

In the tissues of the herpes-infected eye of a rabbit the content of adenosine triphosphoric acid (ATP), glucose and pyroracemic acid decreases and the level of lactic acid rises, i.e. anaerobic glycolysis prevails over the aerobic decomposition of glucose. A sharp decrease in the amount of ATP in the cornea and the iris in herpetic keratitis is due to the increased consumption of ATP for the synthesis of DNA and polypeptides of herpes simplex virus, as well as to disturbances in the oxidation transformations of glucose linked with the increased proportion of anaerobic glycolysis.     

A mutation spectra database for bacterial and mammalian genes: 1998

This database consists of over 24 000 mutations in 18 viral, bacterial, yeast or mammalian genes. The data are grouped as sets of DNA base sequence changes or spectra caused by a particular mutagen under defined conditions. The spectra are available on the World Wide Web at http://info.med.yale.edu/mutbase/ in two formats; in text format that can be browsed on-line or downloaded for use with a text editor and in dBASEIII format for use, after downloading, by relational database programs or by spreadsheets. Researchers are encouraged to submit DNA sequence changes to a suitable mutation database such as ours. A data entry program, MUTSIN, can be retrieved from this site. MUTSIN diagrams each mutation on the computer screen and alerts the user to any discrepancies.     

A Semi‐Batch Process for Nitroxide Mediated Radical Polymerization

Summary: A semi‐batch process using nitroxide mediated polymerization, was explored for the design of low molecular weight solvent‐borne coatings, typical of those used in the automotive industry. While living radical polymerization (LRP) offers many advantages in the control of polymer chain microstructure that may confer important physical and chemical property benefits to coatings, adapting LRP to a semi‐batch process poses significant challenges in the design and operation of the process. Using styrene monomer, various two‐component initiating systems (free radical initiator, 4‐hydroxy‐TEMPO) were studied to understand the effects of different initiators on the course of polymerization. In addition, an alkoxyamine was synthesized and used as the initiating source. The initiators Luperox 7M75 and Luperox 231 give higher polymerization rates and reasonable control over polymerization, while benzoyl peroxide (BPO), Vazo 67, and the alkoxyamine are less effective. The number of polymer chains in the final product is always less than the theoretical value, reflecting poor initiation efficiency, probably resulting from undesirable termination reactions that become important due to the nature of the semi‐batch process. Adding camphorsulfonic acid (CSA) or charging initiator concurrently with monomer during semi‐batch feed, can increase the polymerization rate while maintaining the living character of the polymerization. The copolymerization of styrene and butyl acrylate is also shown to exhibit living character.

Schematic representation of the exchange reaction to produce N‐TEMPO capped polymer chains.     

The effects of thermal history on the density and mechanical properties of poly(methyl methacrylate)

The purpose of this work was to show that physical aging effects in poly(methyl methacrylate) (PMMA) could be correlated with the nonequilibrium state of the glassy polymer, as measured by dilatometry. Specimens were annealed at a series of temperatures within the glass transition region (90, 95 and 100°C) and quenched or slowly cooled to the test temperature (40 or 60°C). Volume recovery was monitored throughout the experiment by accurate dilatometry, and low strain tensile creep compliance measurements were made simultaneously on specimens subjected to identical thermal treatments. At both test temperatures, creep behavior and volume recovery showed a similar dependence on annealing temperature and time. However, the specific volume alone was not sufficient to characterize the aging behavior of glassy PMMA: it was also necessary to define the path by which the state of the glass was reached. This memory effect, which has a direct parallel in volume recovery, is attributed to the presence of a distribution of retardation times, and accounts for, the seemingly paradoxical observation that the creep compliance can initially increase on aging at a temperature below T_g if the specimen has previously been stored for a long period at a lower temperature.     

Polymerization of olefins through heterogeneous catalysis X: Modeling of particle growth and morphology

The development of a detailed model describing particle growth in olefin copolymerization systems is presented. The Multigrain Model considers in detail monomer sorption, mass transfer, and changing porosity within the growing particle, as well as heat and mass transfer across the external film of the particle. The model predicts catalyst performance, including polymerization rates and particle morphology, in different reactor media without parameter adjustment. Internal void fractions are calculated through an examination of the relative growth rates within the growing particle. The model is used to examine the effects of mass transfer limitations, prepolymerization, and nonuniform metal distribution on the particle growth process. Model predictions of morphology show the same trends as observed experimentally.     

A critique of the application of sensory integration therapy to children with learning disabilities

Sensory integration (SI) therapy is a controversial--though popular--treatment for the remediation of motor and academic problems. It has been applied primarily to children with learning disabilities, under the assumption that such children (or at least a subgroup of them) have problems in sensory integration to which some or all of their learning difficulties can be ascribed. The present article critically examines the related issues of whether children with learning disabilities differentially exhibit concomitant problems in sensory integration, and whether such children are helped in any way by means specific to SI therapy. An overview of theoretical contentions and empirical findings pertaining to the first issue is presented, followed by a detailed review of recent studies in the SI therapy research literature, in an effort to resolve the second issue. Results of this critique raise serious doubts as to the validity or utility of SI therapy as an appropriate, indicated treatment for the clinical population in question--and, by extension, for any other groups diagnosed as having "sensory integrative dysfunction." It is concluded that the current fund of research findings may well be sufficient to declare SI therapy not merely an unproven, but a demonstrably ineffective, primary or adjunctive remedial treatment for learning disabilities and other disorders.     

Inhibition of neuronal calcium channels by a novel peptide spider toxin, DW13.3

Peptide toxins have proved to be useful agents, both in discriminating between different components of native calcium channel currents and in the molecular isolation and designation of their cloned channel counterparts. Here, we describe the isolation and characterization of the biochemical and physiological properties of a novel 74-amino acid peptide toxin (DW13.3) extracted from the venom of the spider Filistata hibernalis. The subtype specificity of DW13.3 was investigated using calcium channel currents recorded from two separate expression systems and several different cultured mammalian cell preparations. Overall, DW13.3 potently blocked all native calcium channel currents studied, with the exception of T-type currents recorded from GH3 cells. Examination of transiently expressed calcium channels in oocytes showed that DW13.3 had the highest affinity for alpha1A, followed by alpha1B > alpha1C > alpha1E. The affinity of DW13.3 for alpha1B N-type currents varied by 10-fold between expressed channels and native currents. Although block occurred in a similar 1:1 manner for all subtypes, DW13.3 produced a partial block of both alpha1A currents and P-type currents in cerebellar Purkinje cells. Selective occlusion of the P/Q-type channel ligand omega-conotoxin MVIIC (but not omega-agatoxin IVA) from its binding site in Purkinje neurons suggests that DW13.3 binds to a site close to the pore of the channel. The inhibition of different subtypes of calcium channels by DW13.3 reflects a common "macro" binding site present on all calcium channels except T-type.     

Signaling role of PDE isozymes in pathobiology of glomerular mesangial cells. Studies in vitro and in vivo

Mesangial cells (MC) of renal glomeruli respond to immune-inflammatory injury by accelerated proliferation and generation of reactive oxygen metabolites (ROM). We studied in vivo and in vitro roles of cAMP-protein kinase A (PKA) signaling in modulation of these pathobiologic processes with focus on PDE isozymes. Mitogenic synthesis of DNA in mesangial cells grown in primary culture was blocked by forskolin and dibutyryl cyAMP. Incubation of MC with PDE-3 inhibitors, cilostamide and lixazinone, inhibited (> 50%) mitogenesis, whereas inhibitors of PDE-4, rolipram and denbufylline, caused little or no inhibition. Conversely, inhibitors of PDE-4 suppressed generation of ROM in MC, whereas inhibitors of PDE-3 had no effect. Incubation of mesangial cells with cilostamide or with rolipram increased in situ activity of PKA, and effects of the two inhibitors were additive. PDE inhibitors also decreased activity of mitogen-activated protein kinase. The efficacy of PDE isozyme inhibitors (IC50) to suppress mitogenesis or ROM generation paralleled IC50 for inhibition of cAMP hydrolysis by extracts from mesangial cells. Administration of lixazinone or lixazinone in combination with rolipram to rats with mesangial proliferative glomerulonephritis induced by antithymic serum suppressed proliferation of mesangial cells and also reduced other histopathologic manifestations of the disease. Based on these observations, we propose that in MC, a cAMP pool that is hydrolyzed by PDE-3 inhibits by negative crosstalk via activation of PKA, mitogen-activated protein kinase (MAPK) pathway, and mitogenesis; whereas cAMP pool linked to PDE-4 inhibits, also via activation of PKA, ROM generation in mesangial cells. Results also suggest that PDE isozyme inhibitors, in particular inhibitors of PDE-3, should be investigated for potential use for "signal transduction pharmacotherapy" of glomerulonephritis.