Common myths of hospice palliative care.
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Analgesia↗
Biomedical subjects
Elizabeth Hill
Publications and source records attributed to Elizabeth Hill.
Gp120-alum boosting of a Gag-Pol-Env DNA/MVA AIDS vaccine: poorer control of a pathogenic viral challenge.
Envelope protein immunogens may improve DNA or live-vectored HIV vaccines by complementing antiviral cellular responses with Env antibodies. We tested this concept by administering two immunizations of alum-adjuvanted HIV-1 89.6 gp120 to macaques being primed at weeks 0 and 8 with SHIV 89.6 Gag-Pol-Env DNA and boosted at week 24 with SHIV-89.6 Gag-Pol-Env recombinant modified vaccinia Ankara (MVA). Three hundred micrograms of gp120 was delivered with the second DNA prime and the MVA booster. Eight months after vaccination, all animals were challenged intrarectally with the related, yet serologically distinct, SHIV-89.6P. The gp120 immunizations raised binding, but not neutralizing antibody for the challenge virus, and allowed testing of whether gp120 vaccines that fail to raise neutralizing antibody can improve protection. Following the second gp120 immunization, the plus-gp120 group showed >10 times higher levels of binding antibody than the minus-gp120 group. These levels fell and were overall similar in both groups at the time of challenge. Following the second challenge, both groups had similar temporal patterns and heights of binding and neutralizing antibodies. However, the plus-gp120 group had less consistent control of viremia and higher levels of plasma viral RNA for the first year postchallenge. Assays for complement-dependent enhancing antibody revealed a trend toward higher levels of activity in the plus-gp120 group. This trend did not reach significance in our animal groups of 8. We conclude that gp120 inoculations that fail to raise neutralizing antibody do not improve the efficacy of Gag-Pol-Env DNA/MVA vaccines.
AIDS Vaccines↗
An encoded particle array tool for multiplex bioassays.
The detection of both gene function at the genomic scale and protein assays at a proteomic scale is developing into an essential tool in the discovery and development of new medicines. A wide variety of techniques have been used that allow the analyst to assess the information gathered from a SNP up to a fully developed immunoassay. Despite these advances, there remains an ongoing drive to keep the cost of research and development down to reduce the cost of bringing a new drug or diagnostic to market. The demand to carry out large-scale bioassay analysis using yet smaller reagent volume and at a very low cost per test is gaining much importance as seen in the growing need to perform multiplex bioassays. In this article, we describe an analytical system that is being developed to address such a need for multiplexing bioassays at a low, affordable cost providing a flexible alternative consumable to the current technologies. This novel system utilizes inexpensive fabricated polymeric material produced by standard MEMS technology, which allows the attachment, through a variety of coupling chemistries, of oligonucleotides, proteins, antibodies, and antigens. These can then be analyzed by simple scanning, with either a flow cytometer or a simple optical reader, providing a robust, sensitive microarray assay system.
Oligonucleotide Array Sequence Analysis↗
Heterogeneity of O(6)-alkylguanine-DNA alkyltransferase activity in colorectal cancer: implications for treatment.
OBJECTIVES: MGMT (O(6)-alkylguanine-DNA alkyltransferase) reverses the carcinogenic, mutagenic and cytotoxic effects of alkylating agents. Measurement of MGMT activity in tumours might thus be of use in selecting those patients with colorectal cancer who may be sensitive to adjuvant alkylating agent therapy. The aim of this study was to assess whether measurement of MGMT activity in a single tumour biopsy is representative of the whole tumour. METHODS: Multiple symmetrically spaced biopsies were taken from colorectal cancers obtained from 9 patients. MGMT activity was then measured in cell-free extracts by quantifying the transfer of [(3)H]methyl group from calf thymus DNA methylated in vitro with N-nitroso-N-[(3)H]-methylurea to the MGMT protein. RESULTS: MGMT activity was detected in all tumour samples with the activity ranging between 3.6 and 36.2 fmol/microg DNA and 202-1,986 fmol/mg protein. Heterogeneity in MGMT activity (ratio of maximum/minimum MGMT levels per tumour) varied between 1.3 and 5.4. CONCLUSIONS: Measurement of MGMT activity in a single biopsy is not necessarily indicative of the level throughout the tumour. The response of colorectal cancers to alkylating agent treatment is likely to be non-uniform both within the tumour and between patients.
Adenocarcinoma↗