Biomedical subjects
Publications and source records attributed to R M Phillips.
This article describes a training program that teaches nursing assistants to provide psychosocial care and manage problem behaviors, not just provide basic physical care, for elderly nursing home residents. Addressed are the variety of techniques that can be used to approach nursing assistant students as adult learners in any healthcare setting-long term, acute or home care.
BACKGROUND: The existence of an acidic extracellular pH (pHe) within solid tumours is regarded as a potential target for drug development. The indolequinone EO9 has a complex mechanism of action which includes enhanced potency under acidic pHe conditions in vitro. In order to identify compounds which have a simpler mechanism of action where activation under acidic pHe is the predominant mechanism of toxicity, this study has determined the cytotoxic properties of a series of analogues of EO9 under both physiological and acidic pHe conditions. MATERIALS AND METHODS: H460 human NSCLC cells were exposed to EO compounds under acidic (pH 6.04) and physiological (pH 7.24) pHe conditions for one hour and chemosensitivity assessed 4 days later using the MTT assay. For compounds of interest, DNA damage (both single strand breaks and cross links) in H460 cells was determined using the comet assay. RESULTS: All the compounds tested were more potent under acidic pHe conditions although a broad range of enhancement ratios (defined as the IC50 at pHe 7.24/IC50 at pHe 6.04) were obtained ranging from 3.25 to 116.53. The activity of EO72 was significantly enhanced under acidic conditions and activity was associated with a pH dependent increase in DNA cross linking in H460 cells. As EO72 is a poor substrate for purified human DT-diaphorase, pHe conditions appear to be a major factor determining cell kill. CONCLUSIONS: This study has identified several compounds whose cytotoxic properties in vitro are pHe dependent with EO72 emerging as the lead compound on the basis of the magnitude of the pH dependent chemosensitivity and the fact that it is a poor substrate for DT-diaphorase. Further studies are required to determine whether or not EO72 has suitable pharmacokinetic properties to allow it to reach regions of low pHe within solid tumours.
BACKGROUND: Genes upregulated within the tumour microenvironment represent potential targets for rational drug design. Most studies to date concentrate on the effects of hypoxia, although it is likely many genes are regulated by a more physiological combination of factors. MATERIALS & METHODS: Cells under conditions analogous to the normal and tumour microenvironments were isolated from the plateau-phase system and multicellular spheroids. Gene expression was analysed by differential display and confirmed by Northern blot or semiquantitative RT-PCR. RESULTS: p21-activated kinase (PAK1), a calmodulin-related mRNA, cytochrome oxidase subunit I and an H3.3 histone were upregulated within the in vitro tumour microenvironment, the last 3 within spheroids. CONCLUSIONS: Both models exhibit a range of microenvironmental parameters, although spheroids are more physiological with respect to the presence of extreme hypoxia and the formation of 3-dimensional interactions. We have shown that it is feasible to manipulate the spheroid system by serial trypsinisation to obtain reproducible cell populations for gene expression studies.
An indirect enzyme-linked immunosorbent assay (ELISA) for the detection of antibody to duck hepatitis virus (DHV) is described. The results of ELISA were compared with those of an agar gel diffusion precipitin (AGDP) test and a serum-neutralization (SN) test. The specificity of the ELISA was in accordance with the specificity of the AGDP and SN tests, but there was a difference in sensitivity. The positive detection rates of ELISA, SN test, and AGDP test for 93 clinical samples were 68.8%, 68.8%, and 18.8%, respectively. A positive/negative (P/N) value larger than or equal to 2.1 plus an absorbance value larger than or equal to 0.4 was used as a comprehensive positive standard for the ELISA. This eliminated false-positive reactions. The results showed that the ELISA was a rapid, sensitive, and accurate method for detecting antibody to DHV.
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The relationship between anticentromere antibodies (ACA), antitopoisomerase I or Scleroderma 70 (Scl-70) antibodies, HLA-DR antigens, and clinical manifestations of scleroderma were examined in 51 patients defined by ARA criteria. No association between a given HLA-DR antigen and either ACA or anti-Scl-70 was found. Statistically significant associations were noted for patients with ACA who had a lower frequency of arthritis and longer disease duration; anti-Scl-70 patients were more likely to be males with a higher frequency of pulmonary, cardiac and sicca symptoms.