Guest Editor's Introduction

Journal of Signal Processing Systems -     

Plasmalemmal pH-gradients in drug-sensitive and drug-resistant MCF-7 human breast carcinoma xenografts measured by 31P magnetic resonance spectroscopy

31p Magnetic resonance spectroscopy (MRS) was employed to investigate tumor pH in xenografts of drug-sensitive and drug-resistant MCF-7 human breast carcinoma cells. Measured extracellular pH values were found to be lower than the intracellular pH in all three tumor types investigated. The magnitude of this acid-outside plasmalemmal pH gradient increased with increasing tumor size in tumors of two drug-resistant variants of MCF-7 cells, but not in tumors of the parent (drug-sensitive) cells. The partitioning of weak-base or weak-acid drug molecules across the plasma membrane of a tumor cell is dependent upon the acid-dissociation constant (pKa) of the drug as well as the plasmalemmal pH gradient. A large acid-outside pH gradient, such as those seen in MCF-7 xenografts, can exert a protective effect on the cell from weak-base drugs such as anthracyclines and Vinca alkaloids, which have pKa values of 7.5 to 9.5. The possibility of enhancing the therapeutic efficacy of weak-base drugs by dietary or metabolic manipulation of the extracellular pH, in order to reduce or reverse the plasmalemmal pH gradient, deserves investigation.     

Protein inheritance: lambda plasmid replication perpetuated by the heritable replication complex

BACKGROUND: Replication of a plasmid derived from the Escherichia coli phage lambda initiates by binding of the lambda O protein initiator to the origin of lambda DNA replication, ori lambda. The lambda P protein participates in subsequent steps of assembly of the lambda replication complex. A function of lambda P required for replication complex assembly is inactivated at 43 degrees C by the ts1 mutation. RESULTS: We found that the lambda replication complex assembled at 30 degrees C survives the temperature upshift in lambda crotsPts1 plasmid-harbouring bacteria. We present several lines of evidence that in this system (in which the replication complex assembly does not occur), the replication complex assembled prior to the temperature upshift is inherited by one of two daughter plasmid copies at each replication round for more than 30 cell generations. The 'old' replication complex-driven replication is chloramphenicol-resistant and rifampicin-sensitive. This replication is dependent on lambda O and host dnaK, dnaJ and grpE chaperone gene functions. CONCLUSIONS: The lambda O-containing replication complex is inherited together with DNA and bears information how to initiate the next round of replication at ori lambda; thus, we consider that this phenomenon deserves to be called protein inheritance.     

Properties of metal-dielectric codeposited films

Optical, electrical, mechanical and corrosion properties have been investigated in the following codeposited metal-dielectric systems: CrSiO₂, CuSiO₂ and (Cu, Zn)SiO₂. The studies were performed in a compositional range of 9–95% Cr, 17–87% Au, 87–99% Cu and 65–85% brass. The films were codeposited in an NRC triode sputtering unit where a variable target aperture was used to control the composition during a single pumpdown. The composite film thicknesses ranged from 200 to 1500 Å. The scratch and corrosion resistance and hardness of the composite films showed considerable improvement over the metal component alone. Marked changes were observed in the reflectance and transmittance spectra with relatively small compositional changes. The data on the optical properties including solar reflectance factors DW (nm) and P%, sheet resistance, scratch and corrosion resistance are presented as a function of composition and thickness of the codeposited films.     

Influence of titanium oxide and titanium peroxy gel on the breakdown of hyaluronan by reactive oxygen species

The molecular events occurring at the interface between titanium and connective tissue were investigated in order to help explain the unique biocompatible properties of titanium implants and their successful osseointegration into bone tissue. In this study the influence of commercially pure titanium and titanium peroxy gels on the breakdown of the connective tissue component and serum derived factor, hyaluronan, by reactive oxygen species (ROS), produced during the insertion of an implant in vivo, was examined. Hyaluronan breakdown was monitored in vitro in the presence of a hydroxyl radical flux, generated in the presence and absence of titanium powder and discs. Parallel studies examined the breakdown of hyaluronan by hydroxyl radicals in the presence of a titanium peroxy gel, prepared by incubation of the titanium powder or discs in concentrated hydrogen peroxide. The hyaluronan degradation products were separated according to their hydrodynamic size by gel exclusion chromatography. Similarly, experiments were also performed examining the degradation of 2-deoxy-D-ribose by a hydroxyl radical flux in order to demonstrate the detrimental potential of the hydroxyl radicals and to provide a measure of the effectiveness of titanium and titanium peroxy gels as scavengers of ROS. Titanium reduced the harmful effects of the hydroxyl radicals on the breakdown of hyaluronan, presumably acting as a scavenger for the reactive species, possibly by absorbing them into its surface oxide layer, which spontaneously forms on the surface. In contrast, the formation of a titanium peroxy gel from the titanium powder or on the surface of titanium discs enhanced breakdown of both the hyaluronan chains and 2-deoxy-D-ribose. The implications of these findings with regards to the biocompatible nature of the titanium and the ability of these implants to successfully osseointegrate are discussed.     

Src tyrosine kinase activity is related to luteinizing hormone responsiveness: genetic manipulations using mouse MA10 Leydig cells

The Src family of tyrosine kinases play an important role in various signal transduction pathways in many different cell types, however, the role of these kinases in steroidogenic cells has not been examined. In the present study, genetic approaches were used to directly alter Src tyrosine kinase activity in mouse MA10 Leydig cells in order to determine the effect of changes of Src activity on LH-responsiveness with regard to cAMP and progesterone secretion. MA10 cells expressing a dominant negative Src (MA10(Srck-3)) secreted more cAMP and progesterone in response to LH than control transfected cells. Phosphodiesterase activity was decreased in MA10(Srck-3) cells. Conversely, MA10 cells expressing a temperature sensitive Src (MA10(tsUP)) lost LH-responsiveness with regard to cAMP and progesterone secretion at the Src active temperature (35 degrees C). It is concluded that Src tyrosine kinase has an important role in regulating steroid secretion in MA10 Leydig cells. This regulation may in part be due to Src modulation of phosphodiesterase activity, although other components of the LH-signaling pathway may be involved.     

Clonal evolution of lung tumors

Lung tumors, particularly squamous cell carcinomas, are believed to develop through a series of morphological abnormalities, driven by underlying somatic genetic changes. One way of studying this process is to analyze candidate somatic genetic changes in samples of squamous metaplasia and bronchial dysplasia of varying degrees of severity as well as tumor from the same patient. This assumes a clonal relationship between these lesions. In this article, we provide evidence that adjacent, physically distinct bronchial abnormalities are clonally related. This has been achieved using a plaque assay technique to detect the same p53 mutation, present throughout a tumor specimen, in a small proportion of cells in an adjacent squamous metaplasia. In addition, we have obtained two dysplasia samples from a tumor-free patient over a 9-month interval. The earlier sample had one p53 mutation, whereas the later sample has to p53 mutations on different alleles. Thus, the pattern of clonal evolution detected in the parallel samples mimics the pattern seen in longitudinal samples and supports the analysis of synchronously collected samples for the study of tumor progression.     

Neuronal activity in MST and STPp, but not MT changes systematically with stimulus-independent decisions

Recurrent infection with hepatitis C virus (HCV) is almost universal following orthotopic liver transplantation although clinical severity varies. Data on 135 patients who underwent transplantation for hepatitis C cirrhosis were reviewed. We describe a progressive, severe cholestatic form of hepatitis occurring in a subgroup of patients with recurrent hepatitis C. Ten patients with severe recurrent hepatitis C were identified; 1 has died, 1 awaits retransplantation, and 8 have undergone retransplantation. All 10 developed severe progressive cholestatic hepatitis, with a mean rise in bilirubin to 24.7 mg/dL at the time of retransplantation. Histology at initial recurrence was of mild hepatitis without evidence of rejection. The failed grafts showed either cirrhosis or confluent hepatic necrosis. The onset of cholestasis preceded retransplantation by less than 5 months. Our study suggests that a minority of patients with recurrent hepatitis C after undergoing liver transplantation develop a severe progressive cholestatic hepatitis and liver failure.     

Changes in Specific Heat of Corn Starch Due to Gelatinization

Differential scanning calorimetry (DSC) was used to measure apparent specific heat and heat of gelatinization for corn starch at a 13.4 to 79.1% moisture and 30°C to 100°C. Apparent specific heat of granular and heated starch was determined as a function of moisture content, temperature, and gelatinization. Effect of gelatinization was maximum at 42.3% moisture (wet basis) where the ratio of starch/water caused the largest differences in apparent specific heats. The largest difference corresponded to a degree of gelatinization of 0.429. A model was developed to predict apparent specific heats and provided values with a ±2.57% standard error (compared to experimental values) for heated starch with partial gelatinization over the range from 13.4 to 79.1% moisture.