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Biomedical subjects

C Doyle

Publications and source records attributed to C Doyle.

At least 55 records · Page 3Linked to original sources
PubMed1999

Comparative wear under four different tribological conditions of acetylene enhanced cross-linked ultra high molecular weight polyethylene.

In this study, the wear of ultra high molecular weight polyethylene (UHMWPE) (Grade RCH 1000) crosslinked by gamma irradiation in acetylene was compared to virgin (non-irradiated) UHMWPE using four different wear configurations: (i) unidirectional motion with a smooth counterface, (ii) multidirectional motion with a smooth counterface, (iii) unidirectional motion with a rough counterface and (iv) multidirectional motion with a rough counterface.

Journal Article↗
PubMed1999

The effect of route of immunization on mucosal immunity and protection.

In macaques, the route of immunization has a profound effect on the immune response. Augmenting rectal or vaginal immunization with oral or nasal immunization enhanced the secretory IgA, serum IgG, and T cell responses. However, targeted iliac lymph node (TILN) immunization with recombinant simian immunodeficiency virus (SIV) gp120 and p27 elicited the most consistent mucosal antibody responses in the rectum, vagina, urine, seminal fluid, and blood. Both mucosal and TILN immunization induced specific CD4+ T cell proliferative responses in the iliac lymph nodes, which drain these mucosal surfaces, and in the splenic and circulating T cells. Rectal mucosal challenge with cell-free SIV induced total protection in 4 of 7 macaques that were immunized by the TILN route, and, compared with unimmunized macaques or those immunized by the mucosal route (P<.001), it induced a >90% decrease in virus load in 3 of them. Protection from mucosal rectal infection with SIV was significantly associated with an increase in the CD8 suppressor factor (which was generated by the iliac lymph node), RANTES, and MIP-1beta (P<.01).

Animals↗
PubMed1999

An exploration of the sequence of a 2.9-Mb region of the genome of Drosophila melanogaster: the Adh region.

A contiguous sequence of nearly 3 Mb from the genome of Drosophila melanogaster has been sequenced from a series of overlapping P1 and BAC clones. This region covers 69 chromosome polytene bands on chromosome arm 2L, including the genetically well-characterized "Adh region." A computational analysis of the sequence predicts 218 protein-coding genes, 11 tRNAs, and 17 transposable element sequences. At least 38 of the protein-coding genes are arranged in clusters of from 2 to 6 closely related genes, suggesting extensive tandem duplication. The gene density is one protein-coding gene every 13 kb; the transposable element density is one element every 171 kb. Of 73 genes in this region identified by genetic analysis, 49 have been located on the sequence; P-element insertions have been mapped to 43 genes. Ninety-five (44%) of the known and predicted genes match a Drosophila EST, and 144 (66%) have clear similarities to proteins in other organisms. Genes known to have mutant phenotypes are more likely to be represented in cDNA libraries, and far more likely to have products similar to proteins of other organisms, than are genes with no known mutant phenotype. Over 650 chromosome aberration breakpoints map to this chromosome region, and their nonrandom distribution on the genetic map reflects variation in gene spacing on the DNA. This is the first large-scale analysis of the genome of D. melanogaster at the sequence level. In addition to the direct results obtained, this analysis has allowed us to develop and test methods that will be needed to interpret the complete sequence of the genome of this species. Before beginning a Hunt, it is wise to ask someone what you are looking for before you begin looking for it. Milne 1926

Alcohol Dehydrogenase↗
PubMed1999

Hydroxyapatite-coated femoral stems. Histology and histomorphometry around five components retrieved at post mortem.

We performed a histological and histomorphometric examination in five cadaver specimens of the femoral and acetabular components and the associated tissue which had been recovered between 3.3 and 6.2 years after primary total hip arthroplasty (THA) using a proximal hydroxyapatite (HA)-coated titanium alloy implant. All had functioned well during the patients' life. All the stems were fixed in the femur and showed osseointegration of both the proximal and distal parts. The amount of residual HA was greatest in the distal metaphyseal sections, indicating that the rate of bone remodelling may be the main factor causing loss of HA. The level of activity of the patient was the only clinical factor which correlated with loss of coating. The percentage of bone-implant osseointegration was almost constant, regardless of the amount of HA residue, periprosthetic bone density or the time of implantation. HA debris was seldom observed and if present did not cause any adverse or inflammatory reaction. Partial debonding did occur in one case as a result of a polyethylene-induced inflammatory reaction.

Aged↗
PubMed1998

Coreceptor-independent T cell activation in mice expressing MHC class II molecules mutated in the CD4 binding domain.

We have previously reported that efficient selection of the mature CD4+ T cell repertoire requires a functional interaction between the CD4 coreceptor on the developing thymocyte and the MHC class II molecule on the thymic epithelium. Mice expressing a class II protein carrying the EA137/VA142 double mutation in the CD4 binding domain develop fewer than one-third the number of CD4+ T cells found in wild-type mice. In this report we describe the functional characteristics of this population of CD4+ T cells. CD4+ T cells that develop under these conditions are predicted to be a CD4-independent subset of T cells, bearing TCRs of sufficient affinity for the class II ligand to undergo selection despite the absence of accessory class II-CD4 interactions. We show that CD4+ T cells from the class II mutant mice are indeed CD4 independent in their peripheral activation requirements. Surprisingly, we find that CD4+ T cells from the class II mutant mice, having been selected in the absence of a productive class II-CD4 interaction, fail to functionally engage CD4 even when subsequently provided with a wild-type class II ligand. Nevertheless, CD4+ T cells from EA137/VA142 class II mutant mice can respond to T-dependent Ags and support Ig isotype switching.

Animals↗
PubMed1998

A site for CD4 binding in the beta 1 domain of the MHC class II protein HLA-DR1.

Using a lymphocyte binding assay, we have previously demonstrated that the CD4 protein can mediate cell adhesion by direct interaction with MHC class II molecules. In this report, we have used this assay to test whether synthetic peptides, corresponding to DR beta sequences, could inhibit CD4-class II adhesion. A peptide derived from sequences within the beta1 domain (DR beta 41-55), as well as two peptides derived from sequences within the beta 2 domain (DR beta 121-135 and DR beta 141-155), were shown to inhibit CD4-class II adhesion. Inasmuch as a site for CD4 binding in the beta 2 domain had been previously documented, these studies were designed to investigate the role of the beta 1 domain as an additional site of interaction with CD4. Sixteen site-specific mutations were engineered within the beta1 domain of DR beta 1*0101. Several mutations were shown to disrupt CD4-dependent T cell activation. Based on these results, we propose a model for the molecular interaction of CD4 with MHC class II proteins in which both the beta 1 and beta 2 domains of class II interact with the two amino-terminal Ig-like domains of CD4.

Amino Acid Sequence↗
PubMed1998

Generation of CD8 suppressor factor and beta chemokines, induced by xenogeneic immunization, in the prevention of simian immunodeficiency virus infection in macaques.

Previous xenogeneic immunization experiments in rhesus macaques with simian immunodeficiency virus (SIV) grown in human CD4(+) T cells consistently elicited protection from challenge with live SIV. However, the mechanism of protection has not been established. We present evidence that xenogeneic immunization induced significant CD8 suppressor factor, RANTES (regulated upon activation, normal T cell expressed and secreted), macrophage inflammatory protein (MIP) 1alpha, and MIP-1beta (P < 0.001 - P < 0.02). The concentrations of these increased significantly in protected as compared with infected macaques (P < 0.001). Xenogeneic stimulation in vitro also up-regulated CD8 suppressor factors (SF; P < 0.001) and the beta chemokines which were neutralized by antibodies to the 3 beta chemokines. Recombinant human RANTES, MIP-1alpha and MIP-1beta which bind to simian CCR5, suppressed SIV replication in a dose-dependent manner, with RANTES being more effective than the other two chemokines. The results suggest that immunization with SIV grown in human CD4(+) T cells induces CD8-suppressor factor, RANTES, MIP-1alpha and MIP-1beta which may block CCR5 receptors and prevent the virus from binding and fusion to CD4(+) cells.

Animals↗
PubMed1998

Disruption of the CD4-major histocompatibility complex class II interaction blocks the development of CD4(+) T cells in vivo.

The experiments presented in this report were designed to specifically examine the role of CD4-major histocompatibility complex (MHC) class II interactions during T cell development in vivo. We have generated transgenic mice expressing class II molecules that cannot interact with CD4 but that are otherwise competent to present peptides to the T cell receptor. MHC class II expression was reconstituted in Abeta gene knock-out mice by injection of a transgenic construct encoding either the wild-type I-Abetab protein or a construct encoding a mutation designed to specifically disrupt binding to the CD4 molecule. We demonstrate that the mutation, EA137 and VA142 in the beta2 domain of I-Ab, is sufficient to disrupt CD4-MHC class II interactions in vivo. Furthermore, we show that this interaction is critical for the efficient selection of a complete repertoire of mature CD4(+) T helper cells as evidenced by drastically reduced numbers of conventional CD4(+) T cells in animals expressing the EA137/VA142 mutant I-Ab and by the failure to positively select the transgenic AND T cell receptor on the mutated I-Ab. These results underscore the importance of the CD4-class II interaction in the development of mature peripheral CD4(+) T cells.

Animals↗
PubMed1998

Homing of mononuclear cells from iliac lymph nodes to the genital and rectal mucosa in non-human primates.

The route of immunization may affect the type of immunity that is induced. The objectives of this investigation were to establish in the non-human primate if the internal iliac lymph nodes (LN) function as an inductive site of immunity from which mononuclear cells home to the rectal and cervico-vaginal mucosa. Rhesus macaques were immunized with simian immunodeficiency virus (SIV) core antigen p27 in the proximity of the iliac lymph nodes, and compared with the intramuscular (i.m.) (deltoid or gluteal), and axillary LN routes of immunization. The macaques were then challenged rectally or vaginally by a particulate SIVp27 antigen which was applied to the mucosal surface. The tracking dye PKH26 was injected near the immunizing LN or i.m. site and a week later the mucosal and lymphoid tissues were examined at autopsy. Preferential homing of PKH26-labeled cells from the internal iliac LN to the rectal and vaginal mucosa was demonstrated by flow cytometry after targeted iliac LN (TILN) but not after intramuscular (deltoid) or axillary LN immunization. Homing of the subsets of cells revealed that labeled CD4, CD8 and B cells, as well as monocytes were found in the rectum, colon, vagina or cervix. The results of this investigation shows that the route of immunization may affect regional mucosal immunity. Furthermore, the internal iliac LN may function as an inductive immunological site from which CD4, CD8 and B cells may home preferentially to the rectal, cervical and vaginal mucosa, as well as to the related regional but not the unrelated distal LN.

Animals↗
PubMed1998

Plasma sprayed hydroxyapatite coatings on titanium substrates. Part 1: Mechanical properties and residual stress levels.

Hydroxyapatite (HA) coatings have been sprayed on to substrates of Ti-6Al-4V, using a range of input power levels and plasma gas mixtures. Coatings have also been produced on substrates of mild steel and tungsten, in order to explore certain aspects of the mechanical behaviour of HA without the complication of yielding or creep in the substrate. Studies have been made of the phase constitution, porosity, degree of crystallinity, OH ion content, microstructure and surface roughness of the HA coatings. The Young's moduli in tension and in compression were evaluated by the cantilever beam bend test using a tungsten/HA composite beam. The flexural Young's modulus was determined using a free-standing deposit under the same test. Adhesion was characterised using the single-edge notch-bend test; this is considered superior to the tensile bond strength test in common use. Measured interfacial fracture energies were of the order 1-10 J m(-2). Stress levels were investigated using specimen curvature measurements in conjunction with a numerical process model. The quenching stress for HA was measured to be about 10-25 MPa and the residual stress level in HA coatings at room temperature are predicted to lie in the approximate range of 20-40 MPa (tensile). These residual stresses could be reduced in magnitude by maintaining the substrate at a low temperature (possibly below room temperature) during spraying and it may be worthwhile to explore this. Ideally, the HA coating should have low porosity, high cohesive strength, good adhesion to the substrate, a high degree of crystallinity and high chemical purity and phase stability. In practice, such combinations are rather difficult to achieve by just varying the spraying parameters.

Adhesiveness↗
PubMed1998

Plasma sprayed hydroxyapatite coatings on titanium substrates. Part 2: optimisation of coating properties.

Heat treatment and the introduction of a Ti bond coat have been applied to hydroxyapatite (HA) coatings sprayed using different plasma powers and gas mixtures. Attempts were made in this way to achieve optimal coating properties for orthopaedic implants. In particular, the effects on the degree of crystallinity, the adhesion, the OH ion content and the purity were evaluated. Heat treatment at 700 C for 1 h in air proved to be effective in increasing the crystallinity, regaining the OH- ion and removing other non-HA compounds, although it caused a significant decrease in the degree of adhesion (interfacial fracture toughness) for those specimens sprayed at high powers. This heat treatment was found to induce significant transformation of amorphous HA to the crystalline form, while not detrimentally changing the properties of the underlying Ti-6Al-4V substrates. Precoating with a 100 microm Ti layer increased the adhesion of the HA coatings on Ti-6Al-4V substrates, primarily by providing a rougher surface and promoting better mechanical interlocking. Changes in coating properties during immersion in biological fluids were also studied and were found to depend critically on the chemical composition of the fluids. Small precipitates formed on the coating surfaces when immersed in Ringers solution. These might account for the apparent drop in the degree of crystallinity when measured using X-ray diffraction. A significant drop in the interfacial adhesion was found for those coatings sprayed at high powers. This could be offset by prior precoating with a titanium bond coat and suitable heat treatment. In summary, the following processing sequence is suggested in order to achieve optimum coating properties: precoating the substrate with a layer of Ti (approximately 100 microm), spraying HA at a sufficiently high-power level (depending on particle size and gas mixture) and heat treatment at 700 degrees C for 1 h in air.

Adhesiveness↗
PubMed1998

How best to measure implementation of school health curricula: a comparison of three measures.

The impact of school health education programs is often attenuated by inadequate teacher implementation. Using data from a school-based nutrition education program delivered in a sample of fifth graders, this study examines the discriminant and predictive validity of three measures of curriculum implementation: class-room observation of fidelity, and two measures of completeness, teacher self-report questionnaire and post-implementation interview. A fourth measure, obtained during teacher observations, that assessed student and teacher interaction and student receptivity to the curriculum (labeled Rapport) was also obtained. Predictive validity was determined by examining the association of implementation measures with three study outcomes; health knowledge, asking behaviors related to fruit and vegetables, and fruit and vegetable intake, assessed by 7-day diary. Of the 37 teachers observed, 21 were observed for two sessions and 16 were observed once. Implementation measures were moderately correlated, an indication of discriminant validity. Predictive validity analyses indicated that the observed fidelity, Rapport and interview measures were significantly correlated with post-test student knowledge. The association between health knowledge and observed fidelity (based on dual observation only), Rapport and interview measures remained significant after adjustment for pre-test knowledge values. None of the implementation variables were significantly associated with student fruit and vegetable intake or asking behaviors controlling for pre-test values. These results indicate that the teacher self-report questionnaire was not a valid measure of implementation completeness in this study. Post-implementation completeness interviews and dual observations of fidelity and Rapport appear to be more valid, and largely independent methods of implementation assessment.

Child↗
PubMed1998

Palliative therapy in advanced ovarian cancer: balancing patient expectations, quality of life and cost.

The goals of chemotherapy for recurrent/refractory ovarian cancer are the palliation of disease-related symptoms, and improvement of quality and quantity of life. Previous studies of palliative therapy in advanced ovarian cancer have focused on surrogate measures of patient benefit rather than evaluating palliative end-points such as quality of life and clinical benefit. The impact of palliative chemotherapy on survival, quality of life and cost in advanced ovarian cancer are unknown as there have been no studies comparing palliative treatment with best supportive care. Although there is insufficient information from existing studies to determine whether palliative therapy in advanced ovarian cancer is cost-effective, there is some evidence to suggest that chemotherapy has a role in palliation of symptoms with an apparent improvement in quality of life. We relate the results of two studies. (i) A prospective study evaluating the cost of second/third-line chemotherapy as well as its effectiveness, which found the mean total cost per patient for the study period (one line of chemotherapy) was Canadian $12500. In addition, half of patients seemed to derive some palliative benefit and a quarter of patients had an objective response in their disease. (ii) A retrospective study evaluating all costs from the initiation of palliative chemotherapy until death which demonstrated a cost of Canadian $53000 per patient. Our studies demonstrate that patient expectations of palliative therapy in ovarian cancer are high and patients are willing to put up with significant toxicity for modest benefit. Although palliative therapy may be associated with high costs, even modest prolongation of survival can render such treatment cost-effective. The major cost saving associated with palliative therapy is from the reduced need for hospitalization towards the end of life. Future studies in recurrent/refractory ovarian cancer should focus on palliative end-points and include a comparison with best supportive care.

Antineoplastic Agents↗
PubMed1998

Education and training in residential dementia care in Australia: needs, provision and directions.

This paper summarises existing education and training in dementia for aged care workers in Australia. The majority of aged care workers have no formal qualifications, while those with formal qualifications are mostly from a nursing background. Only half of nursing staff have attended any dementia care training. Existing training is either service based and provided in-house or by private consultants, or tertiary institution based and provided by academics and professional educators. There is considerable in-service and one-off service-based training being provided around Australia, but few of these training exercises are linked to competency standards or staff appraisal. While there are some formal courses addressing training in dementia care available in every state of Australia, the emphasis on dementia care within generalist tertiary institution courses for aged care workers varies considerably.

Australia↗
PubMed1998

Results of the TeachWell worksite wellness program.

OBJECTIVE: This study examined whether providing a school-based teacher wellness program enhances the impact of a health curriculum on student outcomes and improves cognitive, behavioral, and physiological outcomes among participating teachers. METHODS: Thirty-two elementary schools were randomly assigned to experimental or comparison conditions. Comparison group schools received the Gimme-5 program, a curriculum designed to increase fourth and fifty graders' consumption of fruits and vegetables. Experimental schools received Gimme-5 and the teacher wellness program, which included 54 workshops over 2 years, along with several schoolwide health activities. Physiological, behavioral, and cognitive outcomes were assessed in teachers and students. RESULTS: There was no evidence that the intervention favorably modified any student or teacher end points; nor did intervention teachers deliver the Gimme-5 program with greater fidelity than comparison teachers. CONCLUSION: Confidence in the null results is bolstered by the randomized design, baseline sample equivalence, appropriate mixed-model analyses, and lack of selective or differential attrition. Insufficient participation in the wellness program appears a likely explanation for the lack of teacher and student effects. Factors specific to the school setting and intervention may have diminished participation and, thus, intervention effects.

Adult↗
PubMed1998

Protective mucosal immunity elicited by targeted lymph node immunization with a subunit SIV envelope and core vaccine in macaques.

Prevention of sexually transmitted HIV infection was first investigated in non-human primates by mucosal immunization via the rectal, vaginal or male urethral route. This was compared with subcutaneous targeted iliac lymph node (TILN) and systemic intramuscular immunization in non-human primates. TILN immunization elicited the most consistent mucosal sIgA and IgG antibody response in the rectum, vagina, urine and seminal fluid, as well as in blood. Both mucosal and TILN immunization induced a specific CD4+ T cell proliferative response in the iliac lymph nodes which drain these mucosal surfaces, and in the splenic and circulating T cells. In the next experiment macaques were immunized by the TILN route with SIV gp120 and p27 in alum. Rectal mucosal challenge with SIVmac 32H J5 molecular clone (or cell-free virus) induced total protection in four out of seven macaques, compared with infection in 13 of 14 unimmunized macaques or immunized by other routes (p = 0.025). The remaining three macaques immunized by the TILN route showed either decrease in viral load (> 90%) or transient viraemia, indicating that all seven TILN immunized macaques showed total or partial protection of rectal transmission by SIV (p = 0.001). Protection was associated with significant increase in the iliac lymph nodes IgA antibody secreting cells to p27 (p < 0.02), CD8-suppressor factor inhibiting replication of SIV in CD4+ T cells (p < 0.01) and the chemokines RANTES and MIP-1 beta (p < 0.01). We suggest that administration of gp120 and p27 by the TILN route may elicit protective B and T cell immunity which can significantly prevent rectal transmission of SIV or HIV.

Animals↗
PubMed1998

Psychiatric problems in chronic facial pain.

Facial pain patients have been known to describe their life as "a living hell." By employing a biopsychosocial approach, the dental surgeon can often markedly reduce suffering and diminish the negative impact of chronic pain on the patient's day-to-day life, and enhance his or her capacity to deal long-term with this often complex clinical presentation.

Adult↗