Enolase 1 of Candida albicans binds human CD4+ T cells and modulates naïve and memory responses

To obtain a better understanding of the biology behind life-threatening fungal infections caused by Candida albicans, we recently conducted an in silico screening for fungal and host protein interaction partners. We report here that the extracellular domain of human CD4 binds to the moonlighting protein enolase 1 (Eno1) of C. albicans as predicted bioinformatically. By using different anti-CD4 monoclonal antibodies, we determined that C. albicans Eno1 (CaEno1) primarily binds to the extracellular domain 3 of CD4. Functionally, we observed that CaEno1 binding to CD4 activated lymphocyte-specific protein tyrosine kinase (LCK), which was also the case for anti-CD4 monoclonal antibodies tested in parallel. CaEno1 binding to naïve human CD4⁺ T cells skewed cytokine secretion toward a Th2 profile indicative of poor fungal control. Moreover, CaEno1 inhibited human memory CD4⁺ T-cell recall responses. Therapeutically, CD4⁺ T cells transduced with a p41/Crf1-specific T-cell receptor developed for adoptive T-cell therapy were not inhibited by CaEno1 in vitro. Together, the interaction of human CD4⁺ T cells with CaEno1 modulated host CD4⁺ T-cell responses in favor of the fungus. Thus, CaEno1 mediates not only immune evasion through its interference with complement regulators but also through the direct modulation of CD4⁺ T-cell responses.     

Selective incorporation of111In-labeled PHOTOFRIN™ by glioma tissuein vivo

The use of PHOTOFRIN for photodynamic therapy of human gliomas has been studied by i.v. administration and laser photosensitization. Defining the uptake of PHOTOFRIN in the patient's tumor in comparison with the surrounding normal brain tissue is highly desirable for patient selection and study ofin vivo kinetics. We utilized a non-invasive approach to the detection of PHOTOFRIN uptake in brain tumors with¹¹¹In-oxine radiolabeled PHOTOFRIN and external imaging and quantitation using a gamma camera. Biodistribution of¹¹¹In-labeled PHOTOFRIN in 13 organs was determined in four dogs and 15 mice with gliomas.^99mTc-DTPA was used as a control for nonspecific uptake. The greatest concentration of¹¹¹In-PHOTOFRIN in the brain tumor occurred at 24 hours post i.v. administration. The brain tumor PHOTOFRIN uptake was seven times greater than that of normal brain. The decreased blood background at 72 hours made this the optimum time for imaging. Specific tumor tissue uptake of¹¹¹In-PHOTOFRIN occurred, well beyond that resulting from blood-brain-barrier (BBB) breakdown.     

Reliability of level of care decisions in a Long-Term Care program

This paper addresses the question of the degree of agreement between experienced assessors making level-of-care placement decisions for the same client, given a comparable opportunity to obtain and record client information in a community-based Long-Term Care program.A systematic sample of 246 cases was selected, consisting of 47 preadmission assessments and 199 reviews. The resulting data were subjected to analysis using the statistic Kappa and the degree of agreement categories suggested by Fleiss.¹ It was found that at the level-of-care extremes— Extended Care and Personal Care—the agreement between two nurse assessors for reviews could be considered excellent. In the Intermediate Care range, however, the reliability of the level-of-care decision can only be considered fair. Agreement for initial assessments was less, withK=0.469 indicating, overall, only fair agreement. While there was most often only a one-care-level difference between assessors, the program assessor tended to recommend a higher level than the study or check assessor. This has implications for funding agencies and/or facility planners who must assess the likely care requirements of an increasing number of disabled elderly. From a program management perspective, the preceding analyses allow an objective judgement of the extent of the placement decision problem, if any, and further provide a definition of areas most in need of revision. The value of collaboration between practitioner and researcher is evident in these analyses.Dr. Stark is Director, Division of Health Services Research and Development and Assistant Professor, Department of Health Care and Epidemiology, The University of British Columbia. Dr. Gutman is Director, Gerontology Centre and Associate Professor, Faculty of Interdisciplinary Studies, Simon Fraser University. Dr. Brothers is Research Associate, Division of Health Systems, The University of British Columbia. Address enquiries to Dr. A. Stark, Director, Division of Health Services Research and Development, Office of the Coordinator of Health Sciences, The John F. McCreary Health Sciences Centre, 2194 Health Sciences Mall, The University of British Columbia, Vancouver, B.C., V6T 1Z6.The research described in this paper, as well as the larger study of which it is a part, is supported by a grant from the B.C. Health Care Research Foundation. In addition, the cooperation and support of the Ministry of Health, Province of British Columbia is gratefully acknowledged.     

Oral bioavailability of the antioxidant astaxanthin in humans is enhanced by incorporation of lipid based formulations.

Astaxanthin is a carotenoid with antioxidant properties, synthesised by plants and algae, and distributed in marine seafood. Astaxanthin is also available as a food supplement, but, like other carotenoids, is a very lipophilic compound and has low oral bioavailability. However, bioavailability can be enhanced in the presence of fat. There is not much information in the literature about the pharmacokinetics of oral astaxanthin in humans. In this open parallel study, healthy male volunteers received a single dose of 40 mg astaxanthin, as lipid based formulations or as a commercially available food supplement, followed by blood sampling for further analysis of plasma concentrations. Pharmacokinetic parameters were calculated to evaluate the extent and rate of absorption from each formulation. The elimination half-life was 15.9+/-5.3 h (n=32), and showed a mono-phasic curve. Three lipid based formulations: long-chain triglyceride (palm oil) and polysorbate 80 (formulation A), glycerol mono- and dioleate and polysorbate 80 (formulation B), and glycerol mono- and dioleate, polysorbate 80 and sorbitan monooleate (formulation C), all showed enhanced bioavailability, ranging from 1.7 to 3.7 times that of the reference formulation. The highest bioavailability was observed with formulation B, containing a high content of the hydrophilic synthetic surfactant polysorbate 80.