Efficacy of Lentivirus-mediated and MUC1 antibody-targeted VP22-TK/GCV suicide gene therapy for ovarian cancer

Transfer of the herpes simplex virus type I thymidine kinase (HSV-TK) gene into tumor cells using virus-based vectors in conjunction with ganciclovir (GCV) exposure provides a potential gene therapy strategy for the treatment of cancer. Effective gene therapy,, depends on the efficient transfer and specific targeting of therapeutic genes and their protein products to target cells. The purpose of this study was to investigate the anti-tumor effect of Lentivirus-mediated and MUC1 antibody-targeted VP22-TK/GCV suicide gene therapy in animal models. Mouse models were generated with intraperitoneal injection of human epithelial ovarian cancer cells 3AO, which are MUC1-positive. HTV-1-based lentiviral vectors carrying VP22-TK or scFv-VP22-TK were prepared. The animals were injected intraperitoneally with lentivirus containing scFv-VP22-TK, VP22-TK followed by GCV treatment. Combined treatment of lentivirus-expressed scFv-VP22-TK or VP22-TK with GCV inhibited the proliferation and prolonged survival times compared with the control vector. The survival time of animals treated with scFv-VP22-TK/GCV was significantly longer than that of animals treated with VP22-TK/GCV (p = 0.006). Conclusion: Our results suggest that MUC1 antibody-targeted VP22-TK/GCV suicide gene therapy can efficiently inhibit ovarian tumor growth and increase survival in a nude mouse model of ovarian carcinoma. These data support the development of this method for human clinical trials.

Effect of honey types and concentration on starch gelatinization

The complex and variable composition of honey, depending on source, season and processing, means different honey samples could cause variation in the characteristics of the finished product. The objective of this study was to determine how the minor components present in honey affect starch gelatinization. A Rapid Visco Analyser was used to measure changes in viscosity when unmodified maize starch was gelatinized in a honey or model sugar solution. When honey was compared to equivalent blends of sugars, there was an increase in starch viscosity with increasing levels of addition. However, at the same level, honey gave a lower viscosity than the blends of sugars. Honeys from different sources (differing in pH and amylase activity) show a varied effect on starch gelatinization, with starch viscosity increasing with addition level for six of the honeys, but decreasing with increasing addition level for two honey samples. Varying the pH also produced variation in starch gelatinization patterns between honey types. Between pH 3.0 and 4.0, starch viscosity was similar for all four honey types studied, while above this pH there were differences between all honey types. As expected, starch viscosity decreased as the solution pH neared the optimum for honey amylase activity (pH 5.3-5.6), though it did not increase as the pH moved away from the honey amylase activity optimum. Differences between honey samples, and between honey and a model sugar mixture, in their effect on starch gelatinization was attributed to honey amylase activity and the composition and concentration of minor organic compounds present. Crown Copyright (C) 2003 Published by Elsevier Ltd. on behalf of Swiss Society of Food Science and Technology

Suppressing the negative effect of devaluation on group identification: The role of intergroup differentiation and intragroup respect

We examined (N = 76) how social creativity strategies such as intergroup differentiation and intragroup respect suppress the negative impact of threat to an ingroup's value on group identification. Threat was manipulated through false feedback concerning how other groups perceived an ingroup. Both intergroup differentiation and intragroup respect were higher when participants learned that the ingroup was devalued compared to when it was valued. Mediational analyses demonstrated that these factors suppressed the direct negative relationship between value threat and group identification. Discussion focused on the consequences of these social creativity strategies for group identification and collective action. (C) 2004 Elsevier Inc. All rights reserved.

An investigation of the anti-pronation effect of two taping methods after application and exercise

This study investigated the effect of two anti-pronation taping techniques on vertical navicular height, an indicator of foot pronation, after its application and 20 min of exercise. The taping techniques were: the low dye (LD) and low dye with the addition of calcaneal slings and reverse sixes (LDCR). A repeated measures study was used. It found that LDCR was superior to LD and control immediately after application and exercise. LD was better than control immediately after application but not after exercise. These findings provide practical directions to clinicians regularly using anti-pronation taping techniques.

Photodegradation of irinotecan (CPT-11) in aqueous solutions: Identification of fluorescent products and influence of solution composition

The photodegradation of irinotecan (CPT-11), the semisynthetic derivative of the antitumor alkaloid 20(S)-camptothecin, has been investigated. The drug was exposed to laboratory light for up to 5 days in 0.9% saline solution (pH 8.5). Five significant photodegradation products were observed and a high-performance liquid chromatography (HPLC) assay was employed to isolate them from CPT-11 using gradient conditions. The structures were elucidated by nuclear magnetic resonance spectroscopy and tandem mass spectrometry and shown to be the result of extensive modifications of the lactone ring of CPT-11. Three of the compounds were found to belong to the mappicine group of alkaloids. In addition, the effect of light on the stability of CPT-11 in aqueous solutions and biological fluids was also assessed, Potassium phosphate buffers (0.05 M, pH 5.0-8.2) and saline, plasma, urine, and bile solutions containing 20 mu M CPT-11 were equilibrated in the dark for 24 h before being exposed to laboratory light for up to 171 h at ambient temperature. Four of the five identified photodegradation products were observed and quantitated by isocratic HPLC, using a different detection mode (fluorescence) than the one used for gradient elution, In general, CPT-11 was found to be unstable under neutral and alkaline conditions for all solutions investigated, with the exception of bile. We conclude that CPT-11 is photolabile and that care should be taken to protect samples, particularly those intended for the isolation and identification of novel metabolites of CPT-11.

Effect of frother type and concentration on the water recovery and entrainment recovery relationship

A study was undertaken to determine the effects of five industrial frothers on the relationship between entrainment recovery and water recovery. The experiments were conducted using a Batequip rectangular 60-L steel flotation cell that was run in parallel with the first cell in a copper/silver prefloat rougher circuit. The concentration of the frothers ranged from 2.5 to 8.4 g/t. The experiments were repeated at three different froth depths. A power function was found to fit this relationship with no discontinuity in the relationship caused by the changes in frother type and concentration and froth depth.

Effect of power Doppler and digital subtraction techniques on the comparison of myocardial contrast echocardiography with SPECT

Objective-To compare the accuracy and feasibility of harmonic power Doppler and digitally subtracted colour coded grey scale imaging for the assessment of perfusion defect severity by single photon emission computed tomography (SPECT) in an unselected group of patients. Design-Cohort study. Setting-Regional cardiothoracic unit. Patients-49 patients (mean (SD) age 61 (11) years; 27 women, 22 men) with known or suspected coronary artery disease were studied with simultaneous myocardial contrast echo (MCE) and SPECT after standard dipyridamole stress. Main outcome measures-Regional myocardial perfusion by SPECT, performed with Tc-99m tetrafosmin, scored qualitatively and also quantitated as per cent maximum activity. Results-Normal perfusion was identified by SPECT in 225 of 270 segments (83%). Contrast echo images were interpretable in 92% of patients. The proportion of normal MCE by grey scale, subtracted, and power Doppler techniques were respectively 76%, 74%, and 88% (p < 0.05) at > 80% of maximum counts, compared with 65%, 69%, and 61% at < 60% of maximum counts. For each technique, specificity was lowest in the lateral wail, although power Doppler was the least affected. Grey scale and subtraction techniques were least accurate in the septal wall, but power Doppler showed particular problems in the apex. On a per patient analysis, the sensitivity was 67%, 75%, and 83% for detection of coronary artery disease using grey scale, colour coded, and power Doppler, respectively, with a significant difference between power Doppler and grey scale only (p < 0.05). Specificity was also the highest for power Doppler, at 55%, but not significantly different from subtracted colour coded images. Conclusions-Myocardial contrast echo using harmonic power Doppler has greater accuracy than with grey scale imaging and digital subtraction. However, power Doppler appears to be less sensitive for mild perfusion defects.

Effect of hemochromatosis genotype and lifestyle factors on iron and red cell indices in a community population

Background: Heterozygotes for the C282Y mutation of the HFE gene may have altered hematology indices and higher iron stores than wild-type subjects. Methods: We performed a cross-sectional analysis of 1488 females and 1522 males 20-79 years of age drawn from the Busselton (Australia) population study to assess the effects of HFE genotype, age, gender, and lifestyle on serum iron and hematology indices. Results: Male C282Y heterozygotes had increased transferrin saturation compared with the wild-type genotype. Neither male nor female heterozygotes had significantly increased ferritin values compared with the wild-type genotype. Younger (20-29 years) wild-type males, but not heterozygous males, had significantly lower ferritin values than wild-type males in the older age groups. Compound heterozygous subjects had increased means for serum iron, transferrin saturation, corpuscular volume, and corpuscular hemoglobin compared with the wild-type genotype, and the males also had increased ferritin values (medians 323 vs 177 mug/L; P = 0.003). In both male and female wild-type subjects, an increased body mass index was associated with decreased serum iron and transferrin saturation and increased ferritin values. There was a significant increase in ferritin concentrations in both genders with increasing frequency of red meat consumption above a baseline of 1-2 times per week and alcohol intakes >10 g/day. Conclusions: Male C282Y heterozygotes had significantly increased transferrin saturation values. Compound heterozygous (C282Y/H63D) subjects formed a separate category of C282Y heterozygotes in whom both iron and red cell indices were significantly increased compared with the wild-type genotype. (C) 2001 American Association for Clinical Chemistry.

New methods for the assessment of in vitro and in vivo stress cracking in biomedical polyurethanes

This article describes a new test method for the assessment of the severity of environmental stress cracking of biomedical polyurethanes in a manner that minimizes the degree of subjectivity involved. The effect of applied strain and acetone pre-treatment on degradation of Pellethane 2363 80A and Pellethane 2363 55D polyurethanes under in vitro and in vivo conditions is studied. The results are presented using a magnification-weighted image rating system that allows the semi-quantitative rating of degradation based on distribution and severity of surface damage. Devices for applying controlled strain to both flat sheet and tubing samples are described. The new rating system consistently discriminated between. the effects of acetone pre-treatments, strain and exposure times in both in vitro and in vivo experiments. As expected, P80A underwent considerable stress cracking compared with P55D. P80A produced similar stress crack ratings in both in vivo and in vitro experiments, however P55D performed worse under in vitro conditions compared with in vivo. This result indicated that care must be taken when interpreting in vitro results in the absence of in vivo data. (C) 2001 Elsevier Science Ltd. All rights reserved.

The effect of channel geometry and wall boundary conditions on the formation of extrusion surface instabilities for LLDPE

It is believed that surface instabilities can occur during the extrusion of linear low density polyethylene due to high extensional stresses at the exit of the die. Local crack development can occur at a critical stress level when melt rupture is reached. This high extensional stress results from the rearrangement of the flow at the boundary transition between the wall exit and the free surface. The stress is highest at the extrudate surface and decreases into the bulk of the material. The location of the region where the critical level is reached can determine the amplitude of the extrudate surface distortion, This paper studies the effect of wall slip on the numerically simulated extensional stress level at the die exit and correlates this to the experimentally determined amplitude of the surface instability. The effect of die exit radius and die wall roughness on extrusion surface instabilities is also correlated to the exit stress level in the same way. Whereas full slip may completely suppress the surface instability, a reduction in the exit stress level and instability amplitude is also shown for a rounded die exit and a slight increase in instability is shown to result from a rough die wall. A surface instability map demonstrates how the shear rate for onset of extrusion surface instabilities can be predicted on the basis of melt strength measurements and simulated stress peaks at the exit of the die. (C) 2001 Elsevier Science B.V. All rights reserved.

Effect of water temperature and oxygen levels on the diving behavior of two freshwater turtles: Rheodytes leukops and Emydura macquarii

Rheodytes leukops is a bimodally respiring turtle that extracts oxygen from the water chiefly via two enlarged cloacal bursae that are lined with multi-branching papillae. The diving performance of R. leukops was compared to that of Emydura macquarii, a turtle with a limited ability to acquire aquatic oxygen. The diving performance of the turtles was compared under aquatic anoxia (0 mmHg), hypoxia (80 mmHg) and normoxia (155 mmHg) at 15, 23, and 30degreesC. When averaged across all temperatures the dive duration of R. leukops more than doubled from 22.4 +/- 7.65 min under anoxia to 49.8 +/- 19.29 min under normoxic conditions. In contrast, aquatic oxygen level had no effect on the dive duration of E. macquarii. Dive times for both species were significantly longer at the cooler temperature, and the longest dive recorded for each species was 538 min and 166 min for R. leukops and E. macquarii, respectively. Both species displayed a pattern of many short dives punctuated by occasional long dives irrespective of temperature or oxygen regime. Rheodytes leukops, on average, spent significantly less time (42 +/- 2 sec) at the surface per surfacing event than did E. macquarii (106 +/- 20 sec); however, surface times for both species were not related to either water temperature or oxygen level.