The levels of integrin alpha v beta 5 may predict the susceptibility to adenovirus-mediated gene transfer in human lung cancer cells

Adenovirus mediated transfer of growth-inhibiting molecules, such as p53 shows promise as an effective method of suppressing the growth of cancer cells. As the basis for in vivo studies, we examined transfection efficiency using 15 human lung cancer cell lines that differ in their endogenous p53 status. When infected with an adenovirus expressing bacterial beta-galactosidase, the different cell lines showed different levels of beta-galactosidase activity. We found a correlation between the level of integrin alpha v beta 5, which is thought to be an adherence receptor for adenoviruses, and the expression level of the transferred gene, suggesting that gene expression is largely dependent on the infection efficiency. Growth inhibition was induced in all cell lines tested following infection with an adenovirus containing p53, regardless of the genetic status of their endogenous p53 provided a sufficient amount of p53 protein was expressed. Our results (1) confirm that the examination of the susceptibility of target cancer cells to an adenovirus is important when considering performing adenovirus-mediated gene transfer and for evaluating its therapeutic effects; and (2) suggest that the quantification of integrin alpha v beta 5 may be a good way of predicting the susceptibility of cells to adenoviral vectors.     

Effects of pramipexole on contraversive rotation and functional motor impairments in 1-methyl-4-phenyl1,2,3, 6-tetrahydropyridine-induced chronic hemiparkinsonian monkeys

Rotational and functional motor behavioral changes were studied in five MPTP lesioned chronic hemiparkinsonian Macaca nemestrina monkeys after i.m. pramipexole, a predominant D2 subfamily agonist. Pramipexole induced contraversive rotations in a dose-dependent manner with an optimal dose of 56 microg/kg for approximately 2 to 4 hr after injection. Three different rating scales were used to determine drug-induced functional improvement. They included a monkey parkinsonism rating scale, volitional responses to fruit presentations, and number of hand movements that appeared volitional. A dose of 56 microg/kg of pramipexole produced functional improvements on hand disability, and on a parkinsonian rating scale for monkeys in a dose-dependent manner from 32 to 100 microg/kg. These doses produced an increase in significant hand movements in the affected (contralateral) as well as in the normal (ipsilateral) hand to the side of the brain lesion compared with 5% dextrose in water vehicle control. With a dose of 100 microg/kg, the therapeutic effects of pramipexole on hand movements were less than with 56 microg/kg, due to side effects such as scratching.     

Heterogeneity in susceptibility to metronidazole among Helicobacter pylori isolates from patients with gastritis or peptic ulcer disease

Combination therapies that include metronidazole (MTZ) are the most successful therapies used in eradicating Helicobacter pylori. In this study, the prevalence and the relevance of heterogeneity in susceptibility to MTZ among H. pylori populations of 156 patients were evaluated. The results of this study show that 37 patients (24%) were infected with MTZ-resistant H. pylori (MIC > or = 8 micrograms/ml). Furthermore, 33% (52 of 156) of the patients were found to be infected with H. pylori populations heterogeneous for their susceptibility to MTZ. The reassessment of the MICs of MTZ for these 52 H. pylori populations revealed MTZ resistance in 28 of them, increasing the number of MTZ-resistant H. pylori populations among the 156 patients to 65 (42%). Out of 20 isolates, 2 (10%) heterogeneous in their susceptibility to MTZ also appeared to be heterogeneous at the genome level as determined by randomly amplified polymorphic DNA fingerprinting. In conclusion, the results show the limitations and risk of possible misinterpretations when only a single colony, picked from the primary H. pylori populations isolated from patients, is analyzed for its susceptibility to MTZ.     

Model of a miniature pig catheterized for pharmacokinetic and pharmacodynamic studies of anti-infective agents

The purpose of this study was to examine the role of sleep problems in the etiology of nursing caries. Two-hundred mothers of children (104 with nursing caries and 96 caries free) from ages 2 to 4.5 years were surveyed to determine whether difficulty with child sleep and ensuing sleep-associated feeding might be related to the presence of nursing caries. Differences were noted between these two groups regarding: average number of nights the child slept through the night (P < 0.001); total hours of sleep per night (P < 0.05); frequency of night waking episodes (P < 0.01); feeding on demand upon waking (P < 0.01); using a bottle to assist with falling asleep at night (P < 0.001); and feeding in association with nap time (P < 0.001). Differences also were noted in regard to average age of weaning (P < 0.001). Our findings suggest that sleep problems among young children are a behavioral risk factor for night-time bottle use and early childhood caries.     

The relationship of IL-6 to hormonal mediators, fuel utilization, and systemic hypermetabolism after surgical trauma

OBJECTIVES: To define the relationship between inflammatory cytokines, hormonal mediators, alteration of energy substrate and hypermetabolism during the early phase after surgical trauma. DESIGN: A prospective case-control study of 13 patients underwent elective surgery for carcinoma between November 1993 and January 1995. MATERIALS AND METHODS: They received parenteral supply of adequate glucose and amino acids through central venous catheter after surgery equally. Inflammatory cytokines such as TNF- alpha, IL-1 and IL-6, stress hormones such as norepinephrine, glucagon and insulin, and fuel utilization and hypermetabolism variables such as resting energy expenditure (REE), CRP, free fatty acid, respiratory quotient, the calculated rates of glucose and fat oxidation using indirect calorimetry were measured serially (the day before operation, the end of surgery, and postoperative day (POD) 1, 2 and 5). MEASUREMENTS AND MAIN RESULTS: TNF- alpha and IL-1 were not detected during the study period. Initial elevation and steady decline of IL-6 concentrations were seen after surgical injury, and this response related significantly to post-operative norepinephrine and glucagon levels throughout the study period, and to insulin levels only at the end of surgery. %REE (REE/BEEHB; basal energy expenditure according to the Harris-Benedict equation) on POD 2 and 5, and all CRP levels after surgery were significantly related to IL-6 levels more than hormone levels. Fuel utilization variables on POD 2 were related to both IL-6 and hormone levels. CONCLUSIONS: Initial elevation of IL-6 concentration might induce stress hormones such as norepinephrine and glucagon, but not insulin after surgical trauma. Moreover not only hormonal mediators but also cytokine such as IL-6 are responsible for the development of the stress response of the alteration of energy substrate and hypermetabolism.     

Dynamic contributions to the DNA binding entropy of the EcoRI and EcoRV restriction endonucleases

Molecular Dynamics simulations on DNA-EcoRI and DNA-EcoRV complexes suggest that the DNA within these complexes is significantly more ordered than free DNA. Similarly, both the protein and the DNA are more ordered in the specific (cognate) DNA-EcoRV complex than they are in the non-cognate DNA-protein complex, consistent with recently proposed analogies between protein folding and sequence-specific DNA-protein recognition. Analysis of the trajectories shows that the net entropy gain upon specific binding to be the result of opposing contributions. Solvent release, which increases entropy versus configurational terms (as measured by the magnitude of the atomic fluctuations), and collective terms from tight coupling between the motions of the protein and the DNA.     

Leiomyomatosis peritonealis disseminata. Two case reports

AIM: To study the action of quercetin (Que) on inhibiting platelet aggregation. METHODS: Active oxygen free radicals produced by xanthine/xanthine oxidase (Xan/XO) reaction was used, platelet aggregation was determined by the turbidimetric method, and the Xan/XO oxyradicals generating reaction by luminol-dependent chemiluminescence (Che) method. RESULTS: Active oxygen free radicals enhanced the platelet aggregation induced by ADP 1.6 mumol.L-1. The rate of maximal aggregation increased from 29%-38% for ADP to 59%-70% for ADP + Xan/XO. The enhancement was abolished by the treatment of platelet-rich plasma (PRP) with Que 650 mumol.L-1 or hydrocortisone (Hyd) 900 mg.L-1. Both Que and Hyd scavenged the active oxyradicals in vitro. The Che was decreased by 75.7% (Que 4 mumol.L-1) and 79.0% (Hyd 900 mg.L-1) as compared with control. CONCLUSION: Active oxygen free radicals participated in the platelet aggregation, and scavenging oxyradicals by Que was one of mechanisms of inhibiting platelet aggregation.     

On the ontological expressiveness of information systems analysis and design grammars

Abstract. Information systems analysis and design (ISAD) methodologies provide facilities for describing existing or conceived real-world systems. These facilities are ontologically expressive if they are capable of describing all real-world phenomena completely and clearly. In this paper we formally examine the notion of the ontological expressiveness of a grammar and discuss some of its implications for the design and use of ISAD methodologies. We identify some generic ways in which ontological expressiveness may be undermined in a grammar and some potential consequences of these violations. We also examine ontological expressiveness within the context of some other desirable features that might be considered in the design of ISAD methodologies.     

Growth and characterization of hot-wall epitaxial CdTe on (111) HgCdTe and CdZnTe substrates

Thin CdTe films were deposited by hot-wall epitaxy (HWE) on (111) HgCdTe and CdZnTe substrates at temperatures from about 140 to 335°C. X-ray rocking curves were used to show that crystal quality of the CdTe (111)B films improved as substrate temperature increased from 140 to about 250°C. Rocking curve values for full width at half maximum (FWHM) decreased from 2–4 degrees at 140–150°C to less than 100 arc-s at 250°C, and a FWHM of 59 arc-s was the lowest value observed near 250°C. The FWHM of the HWE CdTe was found to be insensitive to growth rate below about 400Å/min, but increased to four degrees at 1250Å/min. X-ray diffraction confirmed that films grown on the B-face at higher temperatures were epitaxial, but contained a significant volume fraction, 35% to 50%, of rotational in-plane twins. Electron microscopy confirmed a coarse twin density, and photoluminescence spectra showed an absence of excitonic emission in the HWE films. Simultaneous growth on two (111) HgCdTe substrates with different surface polarities between 230°C and 335°C showed that deposition rate on the A-face decreased relative to that on the B-face as temperature increased. Films grown on the B-face exhibited better surface morphologies than those grown on the A-face.     

Introducing computer tools into a first course in electricalengineering

At a school where engineering students have immediate access to a personal computer, it is important that they become familiar with that tool early in their studies. In introductory engineering courses it is also important that the students learn to perceive the computer as a tool and not as an end in itself. Achieving these goals requires a careful integration of computer usage into such courses by the instructors. In this paper we examine this issue in the context of a first course in electrical engineering that has been taught at the US Naval Academy, and we present specific examples of assignments we have used in our effort to accomplish these goals