Paget''s disease of bone

The protein encoded by ras and src protooncogenes are frequently activated in a constitutive state in human colorectal cancer. In this study, we investigated the effect of oncogenic p21ras and Py-MT/pp60c-src on the synthesis of syndecan-1, a membrane anchored proteoglycan playing a role in cell-matrix interaction and neoplastic growth control. To this end, we used Caco-2 cells transfected with an activated (Val-12) human Ha-ras gene or the polyoma middle T (Py-MT) oncogene, a constitutive activator of pp60c-src tyrosine kinase activity. As compared to control vector-transfected Caco-2 cells, both oncogene-transfected cells exhibited: (1) a decrease in syndecan-1 specific activity; (2) a decrease in size and sulfation of syndecan-1 ectodomain glycosaminoglycan side chains; and (3) an active heparanase specifically degrading the heparan sulfate chains. In conclusion, the tumorigenic progression induced by oncogenic p21ras or Py-MT/pp60c-src is associated with marked alterations of syndecan-1 at the post-translational level.     

Automating and improving the data quality of a nursing department quality management program at a university hospital

BACKGROUND: The development and implementation of a relational database program for nursing quality management at a university hospital was stimulated by a lack of consistent data management and analysis tools in the existing noncomputerized program. PROGRAM DEVELOPMENT AND IMPLEMENTATION: An initial software prototype implemented in the critical care service included data collection instruments for five areas: medication errors, patient falls, returns to an intensive care unit within 48 hours, hospital-acquired skin breakdown, and unplanned extubations. Access to the database was limited and paper reports only were disseminated on a scheduled basis. In a second phase, the database is being deployed throughout the nursing department using a local area network. Nurse managers will enter and interact with the quality database online and have access to graphics, reports, and action plan development. POSSIBLE ERRORS: A wide range of potential errors influences decisions on how to collect, store, retrieve, and process quality management data. Each type of error affects the nurse manager's ability to identify significant patterns or trends that are amenable to intervention. There is no right way of constructing and implementing a quality improvement database; only an optimum balance between cost, complexity, and efficacy. SUMMARY AND CONCLUSIONS: Initial feedback from end uses has been positive. A three-year experience with a personal computer database suggests that the personal computer-based information technology is appropriate for small to medium applications and can support departmentwide CQI efforts. A case scenario using simulated data is included to illustrate the use of computerized reports in assessing and taking action on an increase in falls.     

A study into the effects of protein binding on nucleotide conformation

In this study, we examine the effects of binding to protein upon nucleotide conformation, by the comparison of X-ray crystal structures of free and protein-bound nucleotides. A dataset of structurally non-homologous protein-nucleotide complexes was derived from the Brookhaven Protein Data Bank by a novel protocol of dual sequential and structural alignments, and a dataset of native nucleotide structures was obtained from the Cambridge Structural Database. The nucleotide torsion angles and sugar puckers, which describe nucleotide conformation, were analysed in both datasets and compared. Differences between them are described and discussed. Overall, the nucleotides were found to bind in low energy conformations, not significantly different from their 'free' conformations except that they adopted an extended conformation in preference to the 'closed' structure predominantly observed by free nucleotide. The archetypal conformation of a protein-bound nucleotide is derived from these observations.     

Nickel- and copper-coated carbon fibre reinforced tin-lead alloy composites

Nickel and copper were deposited over brominated, surface treated, and pristine P-100 carbon fibres using cementation and electroplating techniques. The fibres were brominated by bromine vapour for 48 h and then desorbed at 200 °C in air for 12 h. The anodic oxidation treatment of the fibres involved electrochemical etching in a dilute sodium hydroxide electrolyte for 3 min. Electroplated coated fibres showed better tensile properties than cementation coated fibres. In addition, nickel coating exhibited better bonding with the carbon fibres compared to copper coating. The effect of bromination and surface treatment was improved adhesion between coating and fibres. Nickel- and copper-coated fibres, which were brominated, anodically oxidized, and pristine, reinforced tin-lead alloy composites were fabricated by squeeze casting. The composites containing coated treated carbon fibres had higher tensile and shear strength than the ones containing coated pristine carbon fibres. Moreover, the composite with coated brominated carbon fibres had better tensile strength and shear strength than the surface treatment. The results also showed the composites containing nickel-coated fibres had higher tensile and shear strength than the ones containing copper-coated fibres.     

A monoclonal antibody selected for probing the folding of staphylococcal nuclease and its N-terminal fragments

PURPOSE: Nitric oxide (NO) is generated in mammalian tissue by the conversion of L-arginine to L-citrulline. The reaction is catalyzed by nitric oxide synthase (NOS). NO has been suggested to have a dual role in tumor biology with both antitumor and tumor promoter activity. Furthermore, it has been proposed that NO contributes to interleukin-2-induced antitumor activity. Since interleukin-2 is used in the treatment of renal cell carcinoma (RCC) it was of interest to study the NOS activity in the human kidney and in RCC and its correlation to tumor grade. Furthermore, the effect of cytokine treatment on NOS activity and the effect of NO donor application was studied in cultured cells. MATERIALS AND METHODS: The effect of cytokine treatment on NOS activity and the effect of NO donor application on cell proliferation was studied in cultured human proximal tubular cells and in RCC cell lines HN4 and HN51. NOS activity was measured by the L-arginine to L-citrulline conversion assay. RESULTS: Calcium-dependent NOS activity was found in all non-malignant kidney tissues (486+/-63 pmol. min(-1) g(-1) tissue). The activity was significantly lower in RCC (24+/-6 pmol. min(-1) g(-1) tissue) and correlated with tumor grade; thus high grade tumors showed lower activity than low grade tumors. Calcium-independent NOS activity was not detected in non-malignant kidney tissue or in RCC tissue. In cultured proximal tubular cells and RCC cell lines HN4 and HN51, cytokine treatment induced a marked increase in NOS activity and NO exerted cytostatic effects on these cell lines. Conclusions: The NOS activity was higher in non-malignant kidney tissue than in RCC tissue and was inversely correlated with tumor grade. Furthermore, cytokine treatment induced a marked increase in NOS activity and NO exerted cytostatic effects on cultured proximal tubular cells and RCC cell lines.     

TraceLink: a model of amnesia and consolidation of memory

This investigation examined the feasibility of applying the conductance catheter technique for measurement of absolute aortic segmental volume. Aortic segment volume was estimated simultaneously in vitro by using the conductance catheter technique and sonomicrometer crystals. Experiments were performed in five isolated canine aortas. Vessel diameter and pressure were altered, as were the conductive properties of the surrounding medium. In addition, a three-dimensional finite-element model of the vessel and apparatus was developed to examine the electric field and parallel conductance volume under different experimental conditions. The results indicated that in the absence of parallel conductance volume, the conductance catheter technique predicted absolute changes in segmental volumes and segmental pressure-volume relationships that agreed closely with those determined by sonomicrometry. The introduction of parallel conductance volume added a significant offset error to measurements of volume made with the conductance catheter that were nonlinearly related to the conductive properties of the surrounding medium. The finite-element model was able to predict measured resistance and parallel conductance volume, which correlated strongly with those measured in vitro. The results imply that absolute segmental volume and distensibility may be determined only if the parallel conductance volume is known. If the offset volume is not known precisely, the conductance catheter technique may still be applied to measure absolute changes in aortic segmental volume and compliance.     

Resistance to atracurium in rats with experimental inflammation: role of protein binding

The influence of altered protein binding on the neuromuscular effect of atracurium has been studied in rats with experimental inflammation induced by subcutaneous injection of turpentine oil. Doses of atracurium ranging from 0.45 to 1.5 mg.kg-1 were administered to control (n = 30) and to experimental inflammation induced rats (n = 30). Neuromuscular transmission was monitored by recording the twitch tension of the tibialis-anterior muscle elicited by stimulation of the sciatic nerve. Three effect parameters were recorded: (i) intensity of the effect, measured as percentage depression of baseline twitch tension, (ii) duration of drug action (min) and (iii) recovery time (min). The dose-intensity of the effect relationship was modelled using a sigmoid Emax model. The ED50 (effective dose eliciting 50% of the maximum effect) was significantly increased (P < 0.01) in the inflammation group as compared to the control group (0.94 vs. 0.68 mg.kg-1). This change was reflected in a shift of the dose-response curve to the right in the pretreated rats. For equipotent doses ED95 (defined as the effective dose eliciting 95% of maximum effect), no differences were found in recovery time and duration of action between the two groups of rats. Mucoproteins levels (index of alpha 1-acid glycoprotein (AAG) and protein binding were significantly increased in rats with experimental inflammation as compared to control rats. Based on these results, altered serum protein binding of atracurium appears to be responsible, at least in part, for the resistance to atracurium.