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Biomedical subjects

D Boyd

Publications and source records attributed to D Boyd.

At least 19 recordsLinked to original sources
PubMed2006

An investigation into the structure and reactivity of calcium-zinc-silicate ionomer glasses using MAS-NMR spectroscopy.

The suitability of Glass Polyalkenoate Cements (GPCs) for orthopaedic applications is retarded by the presence in the glass phase of aluminium, a neurotoxin. Unfortunately, the aluminium ion plays an integral role in the setting process of GPCs and its absence is likely to hinder cement formation. However, the authors have previously shown that aluminium-free GPCs may be formulated based on calcium zinc silicate glasses and these novel materials exhibit significant potential as hard tissue biomaterials. However there is no data available on the structure of these glasses. (29)Si MAS-NMR, differential thermal analysis (DTA), X-ray diffraction (XRD), and network crosslink density (CLD) calculations were used to characterize the structure of five calcium zinc silicate glasses and relate glass structure to reactivity. The results indicate that glasses capable of forming Zn-GPCs are predominantly Q(2)/Q(3) in structure with corresponding network crosslink densities greater than 2. The correlation of CLD and MAS-NMR results indicate the primary role of zinc in these simple glass networks is as a network modifier and not an intermediate oxide; this fact will allow for more refined glass compositions, with less reactive structures, to be formulated in the future.

Aluminum↗
PubMed2006

The antibacterial effects of zinc ion migration from zinc-based glass polyalkenoate cements.

Zinc-based glass polyalkenoate cements have been synthesised and their potential use in orthopaedic applications investigated. Zinc ions were released from the materials in a rapid burst over the first 24 h after synthesis, with the release rate falling below detectable levels after 7 days. Cement-implanted bone samples were prepared and the released zinc was shown, using energy dispersive X-ray analysis, to penetrate from the cement into the adjacent bone by up to 40 microm. Finally, the cements exhibited antibacterial activity against Streptococcus mutans and Actinomyces viscosus that reflected the pattern of zinc release, with the inhibition of growth greatest shortly after cement synthesis and little or no inhibition measureable after 30 days.

Actinomyces viscosus↗
PubMed2006

Calcium and zinc ion release from polyalkenoate cements formed from zinc oxide/apatite mixtures.

Calcium and zinc ion release from hydroxyapatite-zinc oxide-poly(acrylic acid) (HAZnO-PAA) composite cements into deionised water was investigated as a function of HA content, PAA concentration, PAA molecular weight and maturation time. At any given maturation time, zinc ion release was constant until the HA content was at the maximum loading (60 wt%) resulting in the cement matrix breaking up, allowing exacerbated ion release. The calcium ion release increased with increased HA content in the composite until the maximum loading where the release drops off. Up to this point, the release of both ionic species was proportional to square root time for the initial 24 hour period, indicating that the release is diffusion controlled. In agreement with related data from conventional Glass Polyalkenoate Cements (GPCs), it is the concentration of the PAA, not the molecular weight, that influences ion release from these materials. However, unlike GPCs, the release of the active ions results in a pH rise in the deionised water, more conventionally seen with Bioglass and related bioactive glasses. It is this pH rise, caused by the ion exchange of Zn(2+) and Ca(2+) for H(+) from the water, leaving an excess of OH(-), that should result in a favourable bioactive response both in vitro and in-vivo.

Apatites↗
PubMed2005

The processing, mechanical properties and bioactivity of zinc based glass ionomer cements.

The suitability of Glass Ionomer Cements (GICs) for use in orthopaedics is retarded by the presence in the glass phase of aluminium, a neurotoxin. Unfortunately, the aluminium ion plays an integral role in the setting process of a GIC and its absence is likely to hinder cement formation. However, zinc oxide, a bacteriocide, can act both as a network modifying oxide and an intermediate oxide in a similar fashion to alumina and so ternary systems based on zinc silicates often have extensive regions of glass formation. The purpose of this research was to produce novel GICs based on calcium zinc silicate glasses and to evaluate their rheological, mechanical and biocompatible properties with the ultimate objective of developing a new range of cements for skeletal applications. The work reported shows that GICs based on two different glasses, A and B (0.05CaO.0.53ZnO.0.42SiO2 and 0.14CaO.0.29ZnO.0.57SiO2, respectively), exhibited handling properties and flexural strengths comparable to conventional GICs. Upon immersion in simulated body fluid of a GIC based on glass B, an amorphous calcium phosphate layer nucleated on the surface of the cement indicating that these cements are bioactive in nature.

Aluminum↗
PubMed2004

Human papilloma virus testing knowledge and attitudes among women attending colposcopy clinic with ASCUS/LGSIL pap smears.

OBJECTIVE: To study women's knowledge regarding the role of human papilloma virus (HPV) in cervical intraepithelial neoplasia and their attitudes toward the integration of HPV testing as part of routine follow-up of atypical squamous cell of uncertain significance/low-grade squamous intraepithelial lesion (ASCUS/LGSIL) abnormalities. METHODS: Over a 12-month period, all women attending the University of Ottawa colposcopy clinic for evaluation and follow-up of ASCUS/LGSIL Pap smears were recruited. Demographic data included age, nature of the Pap smear abnormality, gravidity, parity, occupation and education level, smoking history, previous history of abnormal smears, colposcopic examination and treatment, and current method of contraception. The women were asked to rate their level of concern over their Pap smear abnormality, from 0 (not concerned) to 10 (very concerned). Women's knowledge regarding the role of HPV in cervical intraepithelial neoplasia and the rationale behind the use of HPV testing was assessed by the clinic nurse as being minimal, moderate, or good, as defined by pre-specified criteria. Upon explanation by the nurses of the results of the recent ALTS (ASCUS/LGSIL Triage Study) trial, the women were asked to state whether they preferred to continue with regular colposcopic surveillance every 6 months, or to use the results of the HPV test, if negative, to reduce the number of colposcopy examinations to one annually. Descriptive statistics and logistic regression analysis were used to identify significant demographic factors associated with the women's preference for incorporation of HPV testing in their follow-up. All P values less than.10 were considered to be statistically significant, due to the exploratory nature of the study. RESULTS: Of the 100 women who participated in the study, 42% presented with ASCUS. The mean age (+/- SD) of the women was 33.63 +/- 11.25 years (range, 18-75 years); 66% were office workers with at least a community college degree, 86% reported previous abnormal Pap smears, and 67% had previously been seen for colposcopy. Fifty-eight percent of the women rated their concern level as being 6 or more, while 15% ranked their concerns as maximal at 10. In terms of knowledge about HPV, 75% of the women had no or very minimal knowledge of the role of HPV in cervical intraepithelial neoplasia. With regard to HPV testing, 84% of the study group had either never heard of the test or had only a minimal knowledge of HPV testing. After being informed of the ALTS results, 64% of the women chose to use HPV testing to help in triaging the needs for frequent colposcopy. Logistic regression modelling showed that a college level education (odds ratio [OR], 2.27; 95% confidence interval [CI], 0.95-;5.45; P =.06) and history of previous treatment for abnormal Pap smears (OR, 3.31; CI, 0.88- 12.46; P =.07) were closely associated with the adoption of HPV testing in clinical management. CONCLUSION: There exists a significant lack of knowledge about HPV and its role in the pathogenesis of cervical intraepithelial neoplasia. Women who have received previous treatments for cervical intraepithelial neoplasia and those with college-level educations were more likely to adopt this new technology as part of their care.

Adolescent↗
PubMed2004

Zinc ion release from novel hard tissue biomaterials.

Zinc polyalkenoate cements (ZPCs) and glass polyalkenoate cements (GPCs) are used routinely in dentistry, but have potential for orthopaedic applications as they set at body temperature without shrinkage or significant heat evolution. However, the materials have drawbacks; ZPCs are biocompatible in implant studies, but a fibrous collagen capsular layer forms adjacent to the cement. GPCs are bioactive in the bone environment as a result of the release of calcium, phosphate and fluoride ions, as well as the formation of a silicious gel phase, but research has shown that aluminum ions released result in defective bone mineralisation and as a consequence the ability of these cements to chemically bond to bone is lost. Two approaches have been developed to overcome these problems. The ZPC route considers a ZnO : hydroxyapatite (HA) : poly(acrylic acid) (PAA) mixture, the HA incorporated to improve bioactivity. The GPC route employs a calcium zinc silicate glass; the zinc taking the role that aluminum plays in conventional GPCs. This study has shown that cements can be formulated by an acid base reaction between PAA and both calcium zinc silicate glasses (GPCs) and a mixture of hydroxyapatite and zinc oxide (ZPCs). The moduli of these cements are comparable to both bone and conventional acrylic cements, highlighting their potential for biomedical applications. Unfortunately, both materials have previously been shown to be toxic by cell culture methods, as a result of high zinc ion release, and so it is necessary to study ion release profiles of the cements in order to determine the magnitude of this release. Considering the ZPCs, the modulus of the cement has an inversely proportional relationship to the zinc ion release. From the data presented it is clear that increases in polymer concentration results in lower amounts of zinc ions being released, whilst molar mass of the PAA has no influence. Therefore it would appear that polymer concentration has a significant influence over ion release. Generally, the amount of Zn(2+) released decreases with increasing HA content and/or decreasing ZnO content. Considering the GPCs, the materials are all seen to release large amounts of the active ion, when compared to the commercial versions. The extent of this release increases with temperature and agitation. The release could be minimised by an increased P : L mixing ratio, and an increased PAA concentration, which would produce a more cross-linked cement matrix. Minimising the release of the active ion should improve the in vitro bioactivity of both materials. However, for a full understanding of the clinical benefits of such materials, an in vivo study would be required.

Biocompatible Materials↗
PubMed2002

An inhibitor of c-jun aminoterminal kinase (SP600125) represses c-Jun activation, DNA-binding and PMA-inducible 92-kDa type IV collagenase expression.

The 92-kDa type IV collagenase (MMP-9) contributes to tumor invasion and metastases and strategies to down-regulate its expression could ultimately be of clinical utility. Although the expression of this collagenase is regulated by numerous growth factors, the signaling pathways that transduce these signals are fewer in number and therefore represent pharmacological targets. In this regard, we previously reported that MMP-9 expression was regulated by the c-jun amino terminal kinase (JNK) signaling cascade. Therefore, we undertook a study to determine the efficacy of a novel compound (SP600125), which binds to the ATP binding site of all known JNKs, in repressing MMP-9 expression. In OVCAR-3 cells, SP600125 inhibited the PMA-dependent secretion of MMP-9 in a time-dependent manner and over a dose range that blocked c-Jun phosphorylation and AP-1 binding. SP600125 repressed the activity of a PMA-stimulated MMP-9 promoter-driven luciferase reporter, suggesting that diminished secretion of this collagenase reflected reduced transcription. Further, the activity of a GAL4-driven reporter in PMA-treated cells, co-transfected with an expression construct encoding the trans-activation domain of c-Jun fused to the DNA binding domain of GAL4, was repressed by SP600125. These findings indicate the efficacy of SP600125 in inhibiting c-Jun activation, DNA-binding and the PMA-dependent induction of MMP-9 expression.

Anthracenes↗
PubMed2002

A modified hepatitis B virus core particle containing multiple epitopes of the Plasmodium falciparum circumsporozoite protein provides a highly immunogenic malaria vaccine in preclinical analyses in rodent and primate hosts.

Despite extensive public health efforts, there are presently 200 to 400 million malaria infections and 1 to 2 million deaths each year due to the Plasmodium parasite. A prime target for malaria vaccine development is the circumsporozoite (CS) protein, which is expressed on the extracellular sporozoite and the intracellular hepatic stages of the parasite. Previous studies in rodent malaria models have shown that CS repeat B-cell epitopes expressed in a recombinant hepatitis B virus core (HBc) protein can elicit protective immunity. To design a vaccine for human use, a series of recombinant HBc proteins containing epitopes of Plasmodium falciparum CS protein were assayed for immunogenicity in mice [A. Birkett, B. Thornton, D. Milich, G. A. Oliveira, A. Siddique, R. Nussenzweig, J. M. Calvo-Calle, and E. H. Nardin, abstract from the 50th Annual Meeting of the American Society of Tropical Medicine and Hygiene 2001, Am. J. Trop. Med. Hyg. 65(Suppl. 3):258, 2001; D. R. Milich, J. Hughes, J. Jones, M. Sallberg, and T. R. Phillips, Vaccine 20:771-788, 2001]. The present paper summarizes preclinical analyses of the optimal P. falciparum HBc vaccine candidate, termed ICC-1132, which contains T- and B-cell epitopes from the repeat region and a universal T-cell epitope from the C terminus of the CS protein. The vaccine was highly immunogenic in mice and in Macaca fascicularis (cynomolgus) monkeys. When formulated in adjuvants suitable for human use, the vaccine elicited antisporozoite antibody titers that were logs higher than those obtained in previous studies. Human malaria-specific CD4(+)-T-cell clones and T cells of ICC-1132-immunized mice specifically recognized malaria T-cell epitopes contained in the vaccine. In addition to inducing strong malaria-specific immune responses in naïve hosts, ICC-1132 elicited potent anamnestic antibody responses in mice primed with P. falciparum sporozoites, suggesting potential efficacy in enhancing the sporozoite-primed immune responses of individuals living in areas where malaria is endemic.

Amino Acid Sequence↗
PubMed2001

Dynamics of histamine H(3) receptor antagonists on brain histamine metabolism: do all histamine H(3) receptor antagonists act at a single site?

Thioperamide, the prototypical histamine H(3) receptor antagonist, acts at the brain histamine H(3) autoreceptor to promote the release and metabolism of neuronal histamine, resulting in higher brain levels of the metabolite tele-methylhistamine. However, unlike thioperamide, several new histamine H(3) receptor antagonists enter the central nervous system (CNS), block brain histamine H(3) receptors and increase histamine release without increasing brain tele-methylhistamine levels. Experiments were performed presently in an attempt to understand these results. Consistent with previous findings, thioperamide significantly increased the content and synthesis rate of tele-methylhistamine in mouse and rat brain. In contrast, the histamine H(3) receptor antagonists GT-2227 (4-(6-cyclohexylhex-cis-3-enyl)imidazole) and clobenpropit did not affect tele-methylhistamine synthesis rate in mouse whole brain. The histamine H(3) receptor ligand GT-2016 (5-cyclohexyl-1-(4-imidazol-4-ylpiperidyl)pentan-1-one) had no effect on tele-methylhistamine levels in any rat brain region and decreased tele-methylhistamine synthesis rates in the mouse whole brain. To examine the possibility that these histamine H(3) receptor antagonists might prevent the methylation of newly released histamine, they were co-administered with thioperamide to determine their effects on the thioperamide-induced stimulation of tele-methylhistamine synthesis. GT-2016 significantly reduced the thioperamide-induced activation of tele-methylhistamine synthesis in mouse whole brain and in several regions of rat brain. Although further clarification is needed, these results suggest that some histamine H(3) receptor antagonists may promote the release of neuronal histamine, but also act to reduce histamine methylation in vivo by an unknown mechanism.

Analysis of Variance↗
PubMed2001

Genetic selection for and molecular dynamic modeling of a protein transmembrane domain multimerization motif from a random Escherichia coli genomic library.

In order to identify new transmembrane helix packing motifs in naturally occurring proteins, we have selected transmembrane domains from a library of random Escherichia coli genomic DNA fragments and screened them for homomultimerization via their abilities to dimerize the bacteriophage lambda cI repressor DNA-binding domain. Sequences were isolated using a modified lambda cI headpiece dimerization assay system, which was shown previously to measure transmembrane helix-helix association in the E. coli inner membrane. Screening resulted in the identification of several novel sequences that appear to mediate helix-helix interactions. One sequence, representing the predicted sixth transmembrane domain (TM6) of the E. coli protein YjiO, was chosen for further analysis. Using site-directed mutagenesis and molecular dynamics, a small set of models for YjiO TM6 multimerization interface interactions were generated. This work demonstrates the utility of combining in vivo genetic tools with computational systems for understanding membrane protein structure and assembly.

Amino Acid Motifs↗
PubMed2001

Heregulin regulation of urokinase plasminogen activator and its receptor: human breast epithelial cell invasion.

Heregulin-beta1, which binds human epidermal growth factor receptors 3 and 4, promotes motility and invasiveness of breast cancer cells. Considering the established role of urokinase plasminogen activator (uPA) and its receptor (uPAR) in invasion, this study was undertaken to explore the role of heregulin-beta1 in regulating uPA and uPAR in breast cancer invasion. The stimulation by heregulin-beta1 of noninvasive human breast cancer MCF-7 cells induced the expression of uPA mRNA, protein, and its plasminogenic activity. This uPA mRNA expression was blocked by a transcriptional inhibitor, actinomycin D, and does require de novo protein synthesis for its optimal induction in MCF-7 cells, but not in mouse mammary epithelial HC11 cells. Heregulin-beta1 also induced the expression of uPAR mRNA and protein in an actinomycin D-sensitive manner and cycloheximide superinduced the uPAR mRNA. Heregulin-beta1-stimulated signaling initiated the transcription from uPA- and uPAR-promoters. These results suggest that heregulin-beta1 regulation of breast cancer cell invasion may be mediated in part through the up-regulation of uPA and uPAR.

Breast Neoplasms↗
PubMed2001

Adapting the HCUP QIs for hospital use: the experience in New York State.

BACKGROUND: The Agency for Healthcare Research and Quality developed the Healthcare Cost and Utilization Project (HCUP) quality indicators (QIs) in 1994. The Healthcare Association of New York State (HANYS; Albany), which represents more than 500 nonprofit and public hospitals, long-term care facilities, and home health care agencies, has adapted the HCUP QIs since 1997 to produce annual comparative reports for its member hospitals. Specifically designed for internal use, the reports have been well received and have drawn interest from other hospital associations and state health departments. METHODS: The HCUP QIs were applied to the New York State hospital discharge abstract. A risk adjustment model was constructed for each complication measure. Measures of utilization and access to care were adjusted for differences in patient demographics and payer status by indirect standardization. Data are presented in graphic format. Each hospital receives its own report (in both paper copy and CD-ROM) with comparisons to statewide norms, regional averages, and peer group averages. Report prepared for hospital systems include data for each affiliated hospital. CONCLUSIONS: When used appropriately, the HCUP QIs provide valuable information for individual hospitals to assess quality of care and target potential areas for improvement. The HCUP QIs also give hospitals a broad perspective to look beyond their own institutions and develop community-based quality improvement initiatives. Nevertheless, given the limitations that commonly exist with administrative databases and the lack of standard risk adjustment systems, the HCUP QIs are best used for internal purposes and not for public reporting.

Benchmarking↗
PubMed2001

Complete nucleotide sequence of a 43-kilobase genomic island associated with the multidrug resistance region of Salmonella enterica serovar Typhimurium DT104 and its identification in phage type DT120 and serovar Agona.

This study describes the characterization of the recently described Salmonella genomic island 1 (SGI1) (D. A. Boyd, G. A. Peters, L.-K. Ng, and M. R. Mulvey, FEMS Microbiol. Lett. 189:285-291, 2000), which harbors the genes associated with the ACSSuT phenotype in a Canadian isolate of Salmonella enterica serovar Typhimurium DT104. A 43-kb region has been completely sequenced and found to contain 44 predicted open reading frames (ORFs) which comprised approximately 87% of the total sequence. Fifteen ORFs did not show any significant homology to known gene sequences. A number of ORFs show significant homology to plasmid-related genes, suggesting, at least in part, a plasmid origin for the SGI1, although some with homology to phage-related genes were identified. The SGI1 was identified in a number of multidrug-resistant DT120 and S. enterica serovar Agona strains with similar antibiotic-resistant phenotypes. The G+C content suggests a potential mosaic structure for the SGI1. Emergence of the SGI1 in serovar Agona strains is discussed.

Anti-Bacterial Agents↗
PubMed2001

The association between Porphyromonas gingivalis-specific maternal serum IgG and low birth weight.

BACKGROUND: In Alabama, low birth weight (LBW) infants are about 20 times more likely to die before their first birthday compared to normal birth weight infants. While the rate of LBW has been consistently higher among African Americans compared to whites, there has been a gradual increase in LBW for both African Americans and whites over the last 15 years. In an attempt to identify modifiable risk factors for LBW, we have previously reported that a pregnant woman's poor periodontal health may be an independent risk factor for low birth weight. METHODS: A predominantly African American and socioeconomically homogeneous group of 448 women was followed from the second trimester of their first pregnancy. Thirty-nine LBW cases were observed at the end of follow-up. Using 17 preterm LBW cases and 63 randomly selected controls from the above cohort, the periodontal pathogen-specific maternal serum IgG levels during the second trimester of pregnancy were evaluated in relation to birth weight of the infant, while controlling for known risk factors for LBW. RESULTS: Porphyromonas gingivalis (P.g.)-specific maternal serum IgG levels were higher in the LBW group (mean 58.05, SE = 20.00 microg/ml) compared to the normal birth weight (NBW) group (mean 13.45, SE = 3.92 microg/ml; P= 0.004). Women with higher levels of P.g.-specific IgG had higher odds of giving birth to LBW infants (odds ratio [OR] = 4.1; 95% confidence interval [CI] for odds ratio = 1.3 to 12.8). This association remained significant after controlling for smoking, age, IgG levels against other selected periodontal pathogens, and race. CONCLUSIONS: Low birth weight deliveries were associated with a higher maternal serum antibody level against P. gingivalis at mid-trimester.

Adult↗
PubMed2001

Regulation of the uPA gene in various grades of human glioma cells.

Urokinase-type plasminogen (uPA) activator regulates a variety of processes, including morphogenesis, cell differentiation, migration, and invasion. In previous studies, we demonstrated that uPA levels are significantly higher in anaplastic astrocytoma and glioblastoma than in low-grade glioma and normal brain tissue. In the present study, our goal was to determine whether the increase in uPA production in higher-grade gliomas is caused by an increase in mRNA stability or increased transcription of the gene in three human glioma cell lines of various grades (H4, SW1783, UWR3). The half-life of uPA mRNA was about 14 h in UWR3 and 8 h in SW1783 cells. In transient transfection studies of the wild-type -2109-bp human uPA promoter in the different grades of cell lines, the uPA promoter activity was increased two-fold in SW1783, anaplastic astrocytoma cells and six-fold in UWR3 glioblastoma cells, as compared with the uPA promoter activity in low-grade H4 cells. Using human uPA promoter chloramphenicol acetyl transferase (CAT) constructs with mutations of the AP-1 element at -1967 or the PEA-3 cis element at -1973, the activity of the uPA promoter was decreased 4-fold to 10-fold in all three human glioma cell lines. In transient transfection assays, the uPA promoter was stimulated 2.2-fold in UWR3 and SW1783 cells and 3.7-fold in H4 cells in response to phorbol-12-myristat-13-acetate. We further studied the activation and inhibition of uPA promoter by co-expression of a transactivation domain lacking c-jun: a dominant negative ERK1 and ERK2 mutant and a dominant negative c-raf in glioblastoma cell line showed repressed uPA promoter activity compared with the effect of the empty expression vector. We conclude from our findings that increased transcription is the more likely mechanism underlying the increase in uPA production in high-grade gliomas.

Gene Deletion↗