PubMed Health⌕ Search

Biomedical subjects

J Chadwick

Publications and source records attributed to J Chadwick.

16 recordsLinked to original sources
PubMed2000

Non-specific antiviral activity of antisense molecules targeted to the E1 region of human papillomavirus.

Antisense phosphorothioate oligonucleotides (ODN1 0x5 OMe) directed against the E1 start region of human papillomavirus 11 (HPV11) can inhibit papillomavirus induced growth of implanted human foreskin in a mouse xenograft model. Administration of a mismatch control oligonucleotide (ODN9 0x5 OMe), in which guanine was replaced with adenine in the same model, had no effect on papilloma induced growth. However, the apparent antiviral activity of ODN1 0x5 OMe was also shown in a lethal mouse cytomegalovirus (CMV) model, in which the oligonucleotides are not expected to have antisense activity. To understand the mechanisms of action of these oligonucleotides, a mismatch oligonucleotide (ODN61 0x5 OMe) was prepared which retained the CpG motifs of ODN1 0x5 OMe. This was tested in the mouse xenograft model and shown to have moderate inhibitory activity. As a definitive experiment, a comparison was made between the efficacy of the active oligonucleotide ODN1 0x5 OMe against two papilloma viruses HPV11 and HPV40. Both these viruses cause benign genital warts, but differ by four bases in their E1 sequence that was the target for ODN1 0x5 OMe. Papillomavirus induced growth in the mouse xenograft model was inhibited by ODN1 0x5 OMe in both cases, suggesting that oligonucleotide molecules have a non-specific antiviral activity that is not directly related to their antisense sequence.

Animals↗
PubMed1999

Epitope mapping of mouse monoclonal antibodies to the ppUL83 lower matrix phosphoprotein of human cytomegalovirus.

Of nine mouse monoclonal antibodies (MAbs) directed against the lower matrix protein (pp65; ppUL83) of human cytomegalovirus (HCMV), all immunoprecipitated the 65-kDa protein. Only five were reactive by Western blotting, however, and four of these mapped to linear antigenic epitopes located between amino acids 184-195 (MAb C6), 343-357 (MAb C11), 448-462 (MAb C5), and 448-459 (MAb C13). The epitope specificity of the fifth antibody (MAb C3) and the four that recognised nonlinear sites could not be determined. Competition binding studies using HCMV antigen extracted from productively infected human embryonic lung fibroblasts (HELF), in an enzyme immunoassay (EIA), showed that three of the antibodies reactive with linear epitopes and two of those reactive with conformational epitopes (MAbs C3, C6, C11, C14, and C18), were unique in their binding specificities. MAb C4 competed with MAb C8 and MAb C5 competed with MAb C13 for binding to ppUL83. One of the linear epitopes identified, corresponding to amino acids SAFVFPTKDVAL (MAb C6), was an epitope described previously for CD8+ cytotoxic T lymphocytes.

Amino Acid Sequence↗
PubMed1997

Case costing means, measuring and managing now! The journey traveled by a community hospital.

Funding for health care in Ontario is moving from global funding to equity funding. In the future, hospitals will be reimbursed for how efficiently they care for their various patient populations. The Ontario Case Costing Project (OCCP) was a joint venture by the Ontario Hospital Association and the Ministry of Health. Incentive for participation in this project was based on the need to assess efficiencies in caring for patient populations in surgical suites and to obtain Canadian data. Case Costing has the potential to forecast budgets, identify variances and highlight areas for cost savings. Case Costing can also determine cost per surgeon, cost per service, cost per procedure. The nurses at Markham Stouffville Hospital are empowered to enhance the focus of their practice to include managing human resources, processes and materials. This enhanced focus in the Operating Room maximizes efficiency and effectiveness of processes, and allows the organization to provide better service. This article documents the journey and growth of perioperative nurses toward the destination of case costing. Key to this journey is not only the destination, but the growth and change that occurred and enabled perioperative nurses to effectively champion initiatives such as case costing. Opportunities and Threats, a One Page Plan and our recommended learnings will be shared.

Case Management↗
PubMed1994

Serotype-specific and canine distemper virus cross-reactive H-2Kk-restricted cytotoxic T lymphocyte epitopes in the measles virus nucleoprotein.

Immunization of C3H mice with a vaccinia virus (VV) recombinant expressing the measles virus (MV) nucleoprotein (NP) induces an H-2Kk-restricted cytotoxic T lymphocyte (CTL) response. With reference to the predicted peptide epitope motifs binding to this MHC class I molecule, we have used synthetic peptides derived from the primary sequence of the MV NP to establish the identity of the Kk-restricted CTL epitopes. Two octameric peptides, LDRLVRLI (aa 52-59) and VESPGQLI (aa 81-88) sensitized P815-Kk cells to lysis by MV NP-induced CTLs. In contrast to LDRLVRLI, the sequence VESPGQLI is also present in the primary sequence of the NP from the closely related canine distemper virus (CDV). In vitro stimulation of spleen cells from VV NP-immunized mice with the peptides showed that peptide VESPGQLI induced CTLs which could also lyse CDV-infected cells, whereas peptide LDRLVRLI could only lyse cells presenting the MV protein. Different concentrations of peptides were used, and the lysis efficiencies for both epitopes were shown to be of the same order. The value of predicative motifs for determining MHC class I CTL epitopes is discussed.

Amino Acid Sequence↗
PubMed1994

Perinatal mortality and antenatal care.

Perinatal mortality rates are higher in lower social classes. In terms of health, there is no evidence of disappearing social class differentials. Antenatal care has followed the same 'routine' for most of this century. Antenatal care does not meet the needs of those already disadvantaged. Effectiveness and efficiency of antenatal care are poorly researched and evaluated.

Female↗
PubMed1993

Antiandrogen action in the development of androgen insensitivity in S115 mouse mammary tumour cells.

Endocrine therapy for steroid-sensitive tumours often involves administration of steroid antagonists which are designed to bind to the steroid receptor and block steroid action. However, the clinical problem remains the temporary nature of the tumour regression. Since in vitro models suggest that steroid ablation itself can result in loss of steroid sensitivity of tumour cells, these studies aimed to investigate the influence of the antiandrogen ICI 141,307 on this progression. This antiandrogen exhibits both agonist and antagonist actions on androgen-regulated cellular and molecular parameters of S115 mouse mammary tumour cells in culture. Its ability to regulate mouse mammary tumour virus (MMTV) RNA production in these cells confirms that the antiandrogen-receptor complex can not only bind to the steroid response element (SRE) in the MMTV DNA sequences but also activate gene transcription. Despite these molecular abilities of this antiandrogen, it was still unable to maintain androgen sensitivity in the long term. It was able to delay progression to insensitivity of the various steroid-regulated parameters, although the different parameters were delayed for different lengths of time, but ultimately the antiandrogen was unable to prevent loss of any parameters. It is thus concluded that the nature of the ligand is critical for maintenance of steroid sensitivity: only androgen and not antiandrogen will maintain long-term response. Previous molecular models for loss of steroid response suggest that it could result from inactivation of SRE in the genome when no receptor complex is bound. However, loss of response occurred in these experiments even in the presence of an activated receptor complex capable of binding to the SRE. Possible molecular mechanisms and the clinical implications are discussed.

Acetamides↗
PubMed1993

The regulatory problems in estimating the toxicity of wood preservatives to bats.

Bat populations in general are in decline and are protected under the UK Wildlife and Countryside Act, 1981. There is great concern about the effects of wood preservative treatments on (UK) bat populations. The ethics of using wild bats in tests have been questioned. Proposals are now being developed to use a mouse model. However, no laboratory test animal is likely to accurately reflect the metabolism and behaviour of bats which can be considered as atypical within the animal kingdom. English Nature has pioneered a Relative Toxicity Index (RTI) in order to predict the risks to bats from new and existing active ingredients in remedial timber treatments in the absence of toxicological testing on bats. This is based on the oral LD50 (rat) and assumes that rats and bats are equally sensitive to the same active ingredient in different formulations. Under the auspices of the UK Health and Safety Executive an expert group is developing and refining test methods in order to develop a realistic and reliable classification and labelling scheme for bats.

Animals↗