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Biomedical subjects

C Doyle

Publications and source records attributed to C Doyle.

At least 37 records · Page 2Linked to original sources
PubMed2001

Surfactant protein D enhances bacterial antigen presentation by bone marrow-derived dendritic cells.

Surfactant protein (SP) D functions as a soluble pattern recognition molecule to mediate the clearance of pathogens by phagocytes in the innate immune response. We hypothesize that SP-D may also interact with dendritic cells, the most potent antigen presenting cell, to enhance uptake and presentation of bacterial antigens. Using mouse bone marrow-derived dendritic cells, we show that SP-D binds to immature dendritic cells in a dose-, carbohydrate-, and calcium-dependent manner, whereas SP-D binding to mature dendritic cells is reduced. SP-D also binds to Escherichia coli HB101 and enhances its association with dendritic cells. Additionally, SP-D enhances the antigen presentation of an ovalbumin fusion protein expressed in E. coli HB101 to ovalbumin-specific major histocompatibility complex class II T cell hybridomas. The enhancement of antigen presentation by SP-D is dose dependent and is not shared by other collectin-like proteins tested. These studies demonstrate that SP-D augments antigen presentation by dendritic cells and suggest that innate immune molecules such as SP-D may help initiate an adaptive immune response for the purpose of resolving an infection.

Animals↗
PubMed2001

Comparative analysis of two different types of alumina-alumina hip prosthesis retrieved for aseptic loosening.

We compared and quantified the modes of failure and patterns of wear of 11 Mittelmeier and 11 Ceraver-Ostal retrieved alumina-alumina hip prostheses with reference to the corresponding clinical and radiological histories. Macroscopic wear was assessed using a three-dimensional co-ordinate measuring machine. Talysurf contacting profilometry was used to measure surface roughness on a microscopic scale and SEM to determine mechanisms of wear at the submicron level. The components were classified into one of three categories of wear: low (no visible/measurable wear), stripe (elliptical wear stripe on the heads and larger worn areas on the cups) and severe (macroscopic wear, large volumes of material lost). Overall, the volumetric wear of the alumina-alumina prostheses was substantially less than the widely used metal and ceramic-on-polyethylene combinations. By identifying and eliminating the factors which accelerate wear, it is expected that the lifetime of these devices can be further increased.

Adolescent↗
PubMed2001

Hydroxyapatite-coated acetabular components. Histological and histomorphometric analysis of six cups retrieved at autopsy between three and seven years after successful implantation.

BACKGROUND: Important questions remain regarding the use of hydroxyapatite-coated acetabular components in total hip arthroplasty. What is the relation of resorption of the hydroxyapatite coating to enduring fixation? Will unresorbed or dislodged hydroxyapatite particles cause adverse tissue reactions? Retrieval studies of clinically well-functioning acetabular components should help to answer these questions. METHODS: We examined six clinically successful hydroxyapatite-coated cementless acetabular components that were retrieved at autopsy between 3.3 and 6.6 years after implantation. All components were of the same design. The prostheses and the surrounding bone were prepared for qualitative histological and quantitative histomorphometric analysis. The percentage of bone growth onto the implant, the relative bone area around the implant, the extent of residual hydroxyapatite coating, and the coating thickness were measured. RESULTS: All of the cups showed bone ongrowth, with a mean bone-implant contact (and standard deviation) of 36.5% +/- 13.5%. The contact area was the same in all three zones delineated by DeLee and Charnley. The extent and thickness of the hydroxyapatite layer were much reduced in the specimens from older patients and in those associated with a longer duration of implantation. Degradation of the hydroxyapatite coating by osteoclasts was observed. We did not observe loose hydroxyapatite granules far from the coating, nor did we note any adverse tissue reaction to these granules. In contrast, polyethylene debris was noted in approximately half of the empty screw-holes. CONCLUSIONS: Cell-mediated hydroxyapatite resorption seems to be the main reason for loss of hydroxyapatite coating. The area of bone ongrowth was within a certain range (20% to 50%) of the measured surfaces, and it was independent of the amount of hydroxyapatite residue. The hydroxyapatite coating showed a slow rate of resorption with time, without any adverse tissue reactions.

Absorption↗
PubMed2000

Altered intragraft immune responses and improved renal function in MHC class II-deficient mouse kidney allografts.

BACKGROUND: During renal allograft rejection, expression of MHC class II antigens is up-regulated on the parenchymal cells of the kidney. This up-regulation of MHC class II proteins may stimulate the intragraft alloimmune response by promoting their recognition by recipient CD4+ T cells. In previous studies, absence of donor MHC class II antigens did not affect skin graft survival, but resulted in prolonged survival of cardiac allografts. METHODS: To further explore the role of MHC class II antigens in kidney graft rejection, we performed vascularized kidney transplants using donor kidneys from A(beta)b-deficient mice that lack MHC class II expression. RESULTS: At 4 weeks after transplant, GFR was substantially depressed in control allografts (2.18+/-0.46 ml/min/kg) compared to nonrejecting isografts (7.98+/-1.62 ml/min/kg; P<0.01), but significantly higher in class II- allografts (4.38+/-0.60 ml/min/kg; P<0.05). Despite the improvement in renal function, class II- allograft demonstrated histologic features of acute rejection, not unlike control allografts. However, morphometric analysis at 1 week after transplantation demonstrated significantly fewer CD4+ T cells infiltrating class II- allografts (12.8+/-1.2 cells/mm2) compared to controls (25.5+/-2.6 cells/mm2; P=0.0007). Finally, the intragraft profile of cytokines was altered in class II- allografts, with significantly reduced expression of Th2 cytokine mRNA compared to controls. CONCLUSIONS: These results support a role of MHC class II antigens in the kidney regulating immune cells within the graft. Further, effector pathways triggered by class II antigens promote renal injury during rejection.

Animals↗
PubMed2000

The duration of antigen receptor signalling determines CD4+ versus CD8+ T-cell lineage fate.

Signals elicited by binding of the T-cell antigen receptor and the CD4/CD8 co-receptor to major histocompatibility complex (MHC) molecules control the generation of CD4+ (helper) or CD8+ (cytotoxic) T cells from thymic precursors that initially express both co-receptor proteins. These precursors have unique, clonally distributed T-cell receptors with unpredictable specificity for the self-MHC molecules involved in this differentiation process. However, the mature T cells that emerge express only the CD4 (MHC class II-binding) or CD8 (MHC class I-binding) co-receptor that complements the MHC class-specificity of the T-cell receptor. How this matching of co-receptor-defined lineage and T-cell-receptor specificity is achieved remains unknown, as does whether signalling by the T-cell receptors, co-receptors and/or general cell-fate regulators such as Notch-1 contributes to initial lineage choice, to subsequent differentiation processes or to both. Here we show that the CD4 versus CD8 lineage fate of immature thymocytes is controlled by the co-receptor-influenced duration of initial T-cell receptor-dependent signalling. Notch-1 does not appear to be essential for this fate determination, but it is selectively required for CD8+ T-cell maturation after commitment directed by T-cell receptors. This indicates that the signals constraining CD4 versus CD8 lineage decisions are distinct from those that support subsequent differentiation events such as silencing of co-receptor loci.

Animals↗
PubMed2000

The genome sequence of Drosophila melanogaster.

The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

Animals↗
PubMed2000

Up-regulation of beta-chemokines and down-modulation of CCR5 co-receptors inhibit simian immunodeficiency virus transmission in non-human primates.

A non-cognate mechanism of protection against human immunodeficiency virus-1 (HIV-1) infection involves up-regulation of beta-chemokines, which bind and may down-modulate the CCR5 co-receptors, thereby preventing transmission of M-tropic HIV-1. The objective of this investigation was to evaluate this mechanism in vivo in non-human primates. Rhesus macaques were immunized by a modified targeted lymph nodes (TLN) route with recombinant simian immunodeficiency virus (SIV) glycoprotein 120 (gp120) and p27 in alum, and adsorbed recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) with either interleukin (IL)-2 or IL-4. Immunization induced significant increases in the concentrations of CD8 cell-derived suppressor factor (CD8-SF), regulated on activation normal T cells expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1alpha and MIP-1beta, and down-modulation of the proportion of cells expressing CCR5 (r = 0.737, P<0.05). The macaques were then challenged with SIVmac 220 by the rectal mucosal route. The plasma SIVmac RNA showed a significant inverse correlation with the CD8-SF or the concentration of the three beta-chemokines (r = 0.831 and 0.824, P<0.01), but a positive correlation between the proportion of CCR5+ cells and SIVmac RNA (r = 0.613, P = 0.05). These results demonstrate for the first time in vivo that immunization up-regulates beta-chemokines, which may down-modulate CCR5 co-receptors, and both functions are significantly correlated with the viral load. Hence, the non-cognate beta-chemokine-CCR5 mechanism should be considered as complementary to specific immunity in vaccination against HIV.

Animals↗
PubMed2000

Wear of alumina-on-alumina total hip arthroplasties at a mean 11-year followup.

The surface topography of 11 alumina-on-alumina hip arthroplasties retrieved for aseptic loosening at a mean 11-year followup was investigated. Macroscopic wear was assessed using a coordinate measuring machine. Microscopic wear features were evaluated by Talysurf analysis. Scanning electron microscopy was used to look at the alumina microstructure. Components were classified into three groups: (1) low wear with no sign of wear and average arithmetic roughness values below 0.05 microm; (2) stripe wear with a visible oblong worn area on the femoral heads and penetration rates below 10 microm/year; and (3) severe wear with a visible loss of material on both components, showing total roughness values as much as 4 microm and maximum penetrations higher than 150 microm. Alumina quality assessed by grain size measurements and porosity percentages improved progressively from 1977 to 1988. This resulted in a correlated decrease of the microscopic wear magnitude. However, on a macroscopic scale, factors responsible for either a load increase (weight, young age, and male gender) or impairment in the load distribution over the component surfaces (large grain size, nonoptimal initial cup inclination, and cup migration and/or tilting) increased the penetration rates.

Adolescent↗
PubMed2000

Gimme 5 fruit, juice, and vegetables for fun and health: outcome evaluation.

A theory-based multicomponent intervention (Gimme 5) was designed and implemented to impact fourth- and fifth-grade children's fruit, juice, and vegetable (FJV) consumption and related psychosocial variables. Gimme 5 was a randomized controlled intervention trial with school (n = 16 elementary) as unit of random assignment and analysis. Participants included the cohort of students who were in the third grade in the winter of 1994 and students who joined them in the fourth and fifth grades. The intervention included a curriculum, newsletters, videotapes, and point-of-purchase education. Evaluation included 7-day food records and psychosocial measures from students, telephone interviews with parents, and observational assessments. Favorable results were observed for consumption of FJV combined, FJV consumed at weekday lunch, eating FJV self-efficacy, social norms, asking behaviors, and knowledge. A theory-based school nutrition education program can help change children's FJV consumption and impact factors at home that predispose to FJV consumption, but changes were small, and their persistence is unknown.

Child↗
PubMed2000

Gimme 5 fruit and vegetables for fun and health: process evaluation.

Gimme 5 (Georgia) was a school-based nutrition education effectiveness trial to help fourth- and fifth-grade students eat more fruit, 100% juice, and vegetables (FJV). Process evaluation assessed fidelity of implementation, reach, and use of intervention materials and environmental mediators: teacher training, curriculum delivery, participation in family activities, attendance at evening point-of-purchase grocery store activities, and availability and accessibility of FJV at home. Approximately half of the curriculum activities were implemented in fourth and fifth grades. The lowest proportion completed were those most pertinent to behavior change. Eighty-seven percent of parents reported participating in homework activities with their fourth grader, 66% with fifth graders. Sixty-five percent of parents reported viewing a video with their child in both grades. Ten percent attended evening point-of-purchase grocery store activities. The low level of implementation and modest level of participation in family activities suggest that higher levels of behavior change may have occurred if exposure to the intervention had been higher.

Adult↗
PubMed1999

The effect of immunization on chemokines and CCR5 and CXCR4 coreceptor functions in SIV binding and chemotaxis.

The replication of simian immunodeficiency virus (SIV) in acutely infected CD4+ cells can be inhibited in vitro by CD8-suppressor factors (SF) and beta-chemokines induced by immunization of macaques with SIV gp120 and p27 in Alum. A comparison between intradermal, naso-rectal-i.m. and targeted iliac lymph node (TILN) routes showed that immunization by the TILN route elicited the most significant increase in CD8-SF and the beta-chemokines RANTES, MIP-1alpha and MIP-1beta. Increased CD8-SF and beta-chemokines were induced not only in PBMC but also in iliac lymph nodes and spleen of the TILN immunized macaques. Furthermore, CD8-SF and the concentrations of RANTES, MIP-1alpha and MIP-1beta increased with secondary immunizations, suggesting that memory CD8+ cells are involved. Treatment of CD8+ cell culture supernatant with antibodies to RANTES, MIP-1alpha and MIP-1beta neutralized the CD8-SF activity, indicating that blocking the CCR5 by these ligands played an important part in the CD8-SF activity elicited by TILN immunization. Indeed, blocking CCR5 with monoclonal antibodies inhibited SIV replications and MIP-1beta mediated chemotaxis. In contrast, SDF-1 or MAb to CXCR4 failed to suppress SIV replication. However, SDF-1 was able to induce simian PBMC chemotaxis and MAb to CXCR4 inhibited SDF-1 mediated chemotaxis. These results suggest that immunization in macaques induces CD8-SF and beta-chemokines which may prevent SIV infection by blocking the CCR5 coreceptors both in circulating cells and in the rectal and genital draining lymph node cells.

Animals↗
PubMed1999

Induction of inhibitory antibodies to the CCR5 chemokine receptor and their complementary role in preventing SIV infection in macaques.

The seven-transmembrane G-protein-linked CCR5 molecule functions as a major coreceptor for HIV or simian immunodeficiency virus (SIV) infection. Antibodies to CCR5 were studied in rhesus macaques immunized with SIV grown in human CD4(+) T cells. These macaques were completely protected against i.v. challenge with live SIV. Sera from the protected macaques showed significantly greater inhibition of SIV replication (p < 0.001) and macrophage inflammatory protein-1beta-generated CCR5-dependent chemotaxis (p < 0.01) than sera from unprotected macaques, in the absence of significant neutralizing antibodies to SIV. These two functional assays demonstrate serum antibodies to the CCR5 receptors which were specifically inhibited by CCR5-transfected HEK-293 cells. We postulate that anti-CCR5 antibodies may be complementary to beta-chemokines in blocking CCR5 coreceptors to HIV or SIV binding and fusion of CD4(+) cells.

Animals↗
PubMed1999

Direct morphological comparison of vacuum plasma sprayed and detonation gun sprayed hydroxyapatite coatings for orthopaedic applications.

Hydroxyapatite coatings on titanium substrates were produced using two thermal spray techniques vacuum plasma spraying and detonation gun spraying. X-ray diffraction was used to compare crystallinity and residual stresses in the coatings. Porosity was measured using optical microscopy in conjunction with an image analysis system. Scanning electron microscopy and surface roughness measurements were used to characterise the surface morphologies of the coatings. The vacuum plasma sprayed coatings were found to have a lower residual stress, a higher crystallinity and a higher level of porosity than the detonation gun coatings. It is concluded that consideration needs to be given to the significance of such variations within the clinical context.

Aerosols↗
PubMed1999

Analysis of retrieved alumina ceramic components from Mittelmeier total hip prostheses.

This study analyses explanted prostheses from a single surgeon's 16-yr series of Mittelmeier cementless total hip replacements. The patient group was young (patients aged 15-60, average 40) and active. Revision was related to various factors. All components were measured using a Kemco 3D coordinate measurement machine. Wear surfaces and linear wear penetrations of 11 retrieved Mittelmeier Autophor ceramic hip components (average implantation time 8.6 yr, range 1-13 yr) were analysed and the different types of wear identified. Surface analysis was then performed using Talysurf contacting profilometry and scanning electron microscopy. Three types of wear were identified: low wear (1 case), stripe wear (6 cases) and severe wear (4 cases). Stripe wear was characterised as a stripe of worn area on the head up to 150 microns deep whilst the rest of the head showed very low wear. The cups in the stripe wear cases were worn over about 40-50% of the surface. Severe wear cases had very large areas of heavy wear and visible volume loss on both heads and cups. The four cases of severe wear were associated with abnormal clinical histories.

Adolescent↗
PubMed1999

CD8-suppressor factor and beta-chemokine function as a complementary mechanism to cognate immunity.

Protection against SIV or HIV infection requires specific antibodies and T-cell immune responses. However, a complementary mechanism may be involved, in which CD8-suppressor factors (CD8-SF) and the constitutive beta-chemokines may prevent the virus binding and replicating. Indeed, there is evidence that targeted iliac lymph node (TILN) immunisation with SIVgp120 and p27 or xenoimmunisation with SIV grown in human T-cells generates CD8-SF, RANTES, MIP-1alpha and MIP-1beta which are significantly correlated with protection from SIV infection by the rectal mucosal or intravenous route, respectively. Inhibition of SIV replication in vitro is dependent on the concentration of beta-chemokines generated by immunisation. The critical level for inhibition of SIV replication appears to be higher for rectal mucosal than intravenous challenge by SIV. The mechanism of protection in vivo has not been elucidated but it is likely that the beta-chemokines bind to CCR5 coreceptors which are internalised. Thus, CCR5 coreceptors are either blocked or not expressed on the cell surface for SIV to bind and infect.

Animals↗
PubMed1999

An empirical test of language-relevant interventions for dementia.

The focus of this report is the treatment of persons with dementia who are of a non-English-speaking background (NESB). Noisemaking is one behavioral manifestation associated with severe dementia. It can have devastating effects on persons with dementia by limiting their access to activity programs and social interaction, and is also very distressing for professionals and family carers. It can be especially difficult for carers when they do not speak the first (non-English) language of the person with the noisemaking problem, when the person has lost his or her ability to speak English as the dementia progresses. Behavioral interventions have been found to be successful in decreasing the occurrence of noisemaking in some people with severe dementia. This article reports on a study of an elderly Italian woman with dementia. The study used a randomized, alternating-treatments design in order to determine whether an Italian-language intervention would be more effective in reducing her noisemaking than the same intervention given in English. The main result of the study was that the Italian intervention was found to be significantly more effective in reducing noisemaking than the English intervention. Therefore, this exploratory study provides empirical evidence for the increased effectiveness of an intervention program in the patient's original language. The study also demonstrates the need for individualized intervention programs, particularly for NESB patients living in predominantly English-speaking institutions.

Aged↗