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Biomedical subjects

M Wilson

Publications and source records attributed to M Wilson.

At least 55 records · Page 3Linked to original sources

The effects of angiopoietin-1 and -2 on tumor growth and angiogenesis in human colon cancer.

Angiopoietin (Ang) 1 and Ang-2 are important regulators of endothelial cell survival. Current models suggest that an increase in Ang-2 expression in endothelial cells leads to initiation of angiogenesis. We stably transfected HT29 colon cancer cells with cDNA constructs for Ang-1 or -2 or with vector alone, injected the cells s.c. into nude mice, and assessed tumor growth. Immunohistochemical analyses confirmed sustained increases of Ang-1 and -2 in the tumors. The tumors produced by the Ang-2-transfected cells were larger than the tumors produced in the other groups; those tumors also had higher vessel counts and proliferative indices than tumors in the other groups. Tumors produced by the Ang-1 transfectants had fewer vessels and lower tumor cell proliferative indices than tumors in the other groups. These data suggest that imbalances between Ang-1 and -2 that result in a net gain of Ang-2 activity lead to enhanced tumor angiogenesis and growth.

Angiopoietin-1↗

Is the oxidation of high-density lipoprotein lipids different than the oxidation of low-density lipoprotein lipids?

This article gives detailed insight into the kinetics of high-density lipoprotein (HDL) oxidation catalyzed by azobis(2-amidinopropane).dihydrochloride (ABAP) or by copper. ABAP initialized oxidation of human HDL 3-4 times faster than non-human primate HDL with a similar composition. The oxidizability of non-human primate HDL was 1000 times lower than the oxidizability calculated from rate constants derived from liposome oxidation, suggesting that there is a slow step in HDL oxidation not present in liposomes. Saturable binding of copper to HDL was a significant feature of copper-catalyzed oxidation. Binding constants (K(m)) for non-human primate HDL were 2-3-fold lower than those for human HDL. Copper-catalyzed oxidation of non-human primate HDL was slower than that of human HDL, but human HDL(2) and HDL(3) oxidized at about the same rate. Overall, the kinetics describing the oxidation of HDL were mechanistically similar to those reported for LDL, suggesting that HDL lipids were as easily oxidized as LDL lipids and that HDL will be easily oxidized in vivo when exposed to agents that oxidize LDL.

Amidines↗

Nocardia asteroides native valve endocarditis.

A 39-year-old man with a history of injection drug abuse was given a diagnosis of Nocardia asteroides native aortic valve endocarditis, and he required valve replacement therapy, despite having received potent antimicrobial therapy. This is the first reported proven case of native valve endocarditis due to Nocardia species.

Adult↗

Analysis of the effect of changing environmental conditions on the expression patterns of exported surface-associated proteins of the oral pathogen Actinobacillus actinomycetemcomitans.

Actinobacillus actinomycetemcomitans has been specifically implicated in the aetiology of one or more of the periodontal diseases, conditions in which inflammation of the gums is associated with destruction of the alveolar bone supporting the teeth. In these diseases there is loss of attachment of the gums (gingivae) to the teeth forming a periodontal pocket. The microenvironment of this pocket is extremely complex and it is likely that there will be substantial variation in the environmental conditions operating in this habitat. The aim of the current investigation was to study the effect of disease-relevant environmental factors on the production and release of secreted surface- associated proteins of A. actinomycetemcomitans. These secreted proteins contain many of the virulence determinants of this organism. A range of environmental conditions were investigated: growth in a CO(2)-enriched aerobic atmosphere vs anaerobic growth, presence of serum or blood, biofilm vs planktonic mode of growth and iron depletion. Differential expression of a number of the secreted surface-associated proteins was observed under different growth conditions and these included the glycolytic enzyme triose phosphate isomerase. An ability to adapt to prevailing environmental conditions may facilitate the survival of the organism in the changing microIenvironment of the periodontal pocket.

Adaptation, Biological↗

Identification of photolabile outer membrane proteins of Porphyromonas gingivalis.

As the prevalence of antibiotic-resistant strains of bacteria increases, novel ways of treating infections need to be developed. This is particularly pertinent with respect to the periodontal diseases--the most common chronic bacterial infections of man. The use of a photosensitizer in combination with red light has been demonstrated to be effective in killing several human pathogens, including the oral bacterium, Porphyromonas gingivalis, a major pathogen in periodontitis. Killing was associated with alterations in the molecular masses of several outer membrane and plasma membrane proteins and these may be therapeutic targets for photodynamic therapy and other antimicrobial approaches. To identify these photolabile proteins, we have used a panel of monoclonal antibodies raised to whole P. gingivalis. A number of the antibodies recognized various photolabile proteins. Using a combination of Western blotting and protein sequencing the predominant photolabile proteins in P. gingivalis have been identified as the major secreted/cell surface proteases--Lys and Arg gingipain.

Adhesins, Bacterial↗

Antibacterial activity of particulate bioglass against supra- and subgingival bacteria.

Particulate Bioglass is a bioactive material used in the repair of periodontal defects. This material undergoes a series of surface reactions in an aqueous environment which lead to osseointegration. The aim of this study was to determine whether these reactions exerted an antibacterial effect on a range of oral bacteria. Streptococcus sanguis, Streptococcus mutans and Actinomyces viscosus were suspended in nutrient broth (NB), artificial saliva (AS) or Dulbecco's modified eagle medium plus 10% foetal calf serum (DMEM + 10%FCS), with or without particulate Bioglass. All bacteria showed reduced viability following exposure to Bioglass in all the media after 1 h. This antibacterial effect increased after 3 h. Porphyromonas gingivalis, Fusobacterium nucleatum, Prevotella intermedia and Actinobacillus actinomycetemcomitans were suspended in either BM broth or 40% horse serum (HS) in RPMI. A considerable reduction in viability was observed with all bacteria tested, in both media, compared to inert glass controls. In further experiments it was found that the viability of S. sanguis was significantly reduced following exposure to NB pre-incubated with Bioglass. Additionally, it was found that neutralisation of this highly alkaline solution eliminated the antibacterial effect. Moreover, a solution of NB and NaOH (of equivalent pH) exerted an antibacterial effect of similar magnitude to that of the solution pre-incubated with Bioglass. Thus, particulate Bioglass exerts an antibacterial effect on certain oral bacteria, possibly by virtue of the alkaline nature of its surface reactions. This may reduce bacterial colonisation of its surface in vivo.

Actinomyces viscosus↗

Genomic organization and differential expression of channel catfish MHC class I genes.

Two clones, designated Icpu-UA/3 and Icpu-UA/26, were isolated from a genomic library prepared from a single homozygous gynogenetic channel catfish. Sequence analysis showed that each clone encoded a gene product containing features conserved among MHC class I molecules. The genomic organization of both clones indicated that each domain, with the exception of the cytoplasmic, was encoded by a separate exon. Moreover, like mammals, catfish cytoplasmic regions were encoded by three exons rather than two as previously described for other teleost MHC class I genes. Analysis of nucleotide sequences upstream of catfish class I genes revealed the presence of several regulatory motifs similar to those seen in mammalian class I genes. These included a TATA box, Enhancer B, Site alpha, ISRE, and GAS elements. To determine the functional significance of these elements, EMSAs and tissue expression assays were performed. EMSAs demonstrated that an Enhancer B element within Icpu-UA/26, and an imperfect Enhancer B element and/or a GC-rich region within Icpu-UA/3 were responsible for formation of specific DNA/protein complexes. Expression studies detected Icpu-UA/26 transcripts in all tissues tested, whereas Icpu-UA/3 encoded messages were seen in a limited number of tissues. These results define the intron/exon organization of catfish MHC class I genes, suggest that Icpu-UA/3 encodes a nonclassical gene, and provide the first functional evidence that upstream sequences, similar to those seen in mammalian class I genes, play important roles in regulating teleost MHC gene expression.

Amino Acid Sequence↗

Staphylococcus aureus accessory regulators: expression within biofilms and effect on adhesion.

Many of the genes encoding the virulence factors for Staphylococcus aureus are controlled by the accessory gene regulator (agr) and staphylococcal accessory regulator (sar). This regulation may be affected by the environment in which the organisms are grown. In the majority of ecosystems, bacteria grow attached to surfaces and form biofilms. We used S. aureus strains containing mutations inactivating agr and sar to determine whether the presence of these genes influences the attachment of the bacterium to a surface. We also used strains harbouring reporter constructs of the agr and sar operons to determine their expression in biofilms. The attachment study results showed that the sarA mutant strain adhered better to glass than did the agrA mutant or the wild type. There was an increased adherence to fibronectin-coated glass for all three strains compared to glass. Thus, these adhesion studies demonstrate that agr and sar have pleiotrophic effects on the surface expression of molecules responsible for binding to different substrata. In the biofilms higher numbers of bacteria and the greatest expression were observed at the base, but there were no observable differences between the reporter constructs. Expression of the agr and sar reporter fusions was significantly higher in the deepest layers of the biofilms where the greatest numbers of bacteria were also observed, perhaps as one might expect for genes that are regulated in a cell density dependent fashion.

Bacterial Adhesion↗

Amine and tin fluoride inhibition of Streptococcus sanguis adhesion under continuous flow.

This study evaluated the ability of topically applied amine fluoride (AmF) and AmF-tin fluoride to inhibit the adhesion of Streptococcus sanguis within a parallel plate flow cell system. One of three AmF compounds and two tin fluoride preparations significantly reduced the net bacterial adhesion to conditioned glass over a 1-h period. Tin(IV) fluoride inhibited S. sanguis adhesion to the greatest extent, and this was shown to be dependent on the formation of the conditioning film prior to agent application.

Bacterial Adhesion↗

Capnocytophaga granulosa and Capnocytophaga haemolytica: novel species in subgingival plaque.

BACKGROUND: The oral cavity accommodates one of the most diverse microfloras in the human body. Knowledge of this microflora, and of the periodontal microflora in particular, proves crucial towards an understanding of the bacterial-host interactions which lead to the development of infectious inflammatory periodontal diseases. Capnocytophaga species have been implicated as putative periodontal pathogens. To date, only 3 members of this genus (C. gingivalis, C. ochracea and C. sputigena) have been isolated from subgingival plaque. AIM: This communication reports the isolation of 2 recently-speciated strains, namely C. granulosa and C. haemolytica, from subgingival plaque collected from adult periodontitis patients. MATERIAL AND METHODS: Subgingival plaque was collected from 29 patients with chronic adult periodontitis. Plaque samples were inoculated onto fastidious anaerobe agar and incubated anaerobically for 5 days. Routine identification of clinical isolates was performed by 16S rRNA PCR-RFLP analysis, using Cfo I as restriction enzyme and corroborated by 16S rRNA gene sequencing. RESULTS: 16 of 29 patients (55%) tested positive for either C. granulosa and or C. haemolytica. A total of 70 isolates (63 C. granulosa and 7 C. haemolytica) were cultivated from subgingival plaque. 15 (51%) patients tested positive for C. granulosa, and 3 (10%) patients tested positive for C. haemolytica. CONCLUSION: This is the 1st report which recounts the presence of C. granulosa and C. haemolytica in subgingival plaque. Further research is required to establish the relative proportions of these species subgingivally in health and disease.

Adult↗

Perceiving imitatible stimuli: consequences of isomorphism between input and output.

For more than a century, psychologists have been intrigued by the idea that mental representations of perceived human actions are closely connected with mental representations of performing those same actions. In this article, connections between input and output representations are considered in terms of the potential for imitation. A broad range of evidence suggests that, for imitatible stimuli, input and output representations are isomorphic to one another, allowing mutual influence between perception and motoric planning that is rapid, effortless, and possibly obligatory. Thus, the cognitive consequences of imitatibility may underlie such diverse phenomena as phoneme perception; imitation in neonates; echoic memory; stimulus-response compatibility; conduction aphasia; maintenance rehearsal; and a variety of developmental and social activities such as language acquisition, social learning, empathy, and monitoring one's own behavior.

Cognition↗

Bigger is better: maternal and neonatal predictors of hematopoietic potential of umbilical cord blood units.

Umbilical cord blood (CB) is a useful stem cell source for patients without matched family donors. CB banking is expensive, however, because only a small percentage of the cord units stored are used for transplantation. In this study, we determined whether maternal factors, such as race, age, and smoking status have an effect on laboratory parameters of hematopoietic potential, such as viability, cell counts, CD34+ cell counts, and CFU-GM. We studied the effect of neonatal characteristics such as birth order, birth weight, gestational age, and sex of the baby on the same laboratory parameters. Race and maternal age had no effect on these laboratory parameters. In multivariate analysis, babies of longer gestational age had higher cell counts, but lower CD34+ cell counts and CFU-GM. Bigger babies had higher cell counts, more CD34+ cells, and more CFU-GM. Women with fewer previous live births also produced cord units with higher cell counts, CFU-GM, and CD34+ cell counts. Specifically, each 500 g increase in birth weight contributed to a 28% increase in CD34+ cell counts, each week of gestation contributed to a 9% decrease in CD34+cell counts, and each previous birth contributed to a 17% decrease in CD34+ cell counts (all P < 0.05). These data may be used to select the optimal cord blood donors and allow CB banks efficient resource allocation.

Adult↗

An in vitro evaluation of the antimicrobial efficacy of irrigants on biofilms of root canal isolates.

AIM: The bactericidal effect of four antimicrobial agents was investigated against single-species biofilms derived from a range of root canal isolates. METHODOLOGY: Single-species biofilms of Prevotella intermedia, Peptostreptococcus micros, Streptococcus intermedius, Fusobacterium nucleatum and Enterococcus faecalis were generated on membrane filter discs and subjected to 15 min or 1 h incubation with 5 p.p.m. colloidal silver, 2.25% sodium hypochlorite (NaOCl), 0.2% chlorhexidine, 10% iodine or phosphate buffered saline (PBS) as a control. The antimicrobial activity of the agents was neutralized and the bacterial cells were harvested from the discs by vortexing, serially diluted in reduced transport fluid, plated on fastidious anaerobe agar containing 5% horse blood, incubated anaerobically and colony-forming units calculated. RESULTS: Iodine and NaOCl were more effective than chlorhexidine except against P. micros and P. intermedia where they were all 100% effective. Iodine and NaOCl elicited a 100% kill after 1 h incubation for all strains used. However, after 15 min, they showed differing bactericidal effects depending on the strain. None of the agents were effective against F. nucleatum after 15 min but NaOCl, iodine and chlorhexidine were all effective after 1 h. Colloidal silver was generally ineffective. CONCLUSIONS: The effectiveness of a particular agent was dependent on the nature of the organism in the biofilm and on the contact time. NaOCl was generally the most effective agent tested, followed by iodine. However the clinical efficacy of these agents must be considered in light of the complex root canal anatomy and polymicrobial nature of root canal infections.

Anti-Infective Agents, Local↗

A new in vitro model for the study of microbial microleakage around dental restorations: a preliminary qualitative evaluation.

AIM: The aim of this study was to develop an in vitro model to replicate microbial microleakage at a tooth/ restoration interface using a constant depth film fermentor (CDFF). METHODOLOGY: Amalgam restorations were placed in machined bovine dentine cylinders and sealed externally with varnish, leaving a 1-mm perimeter exposed around the tooth/restoration interface. The dentine cylinders were housed in a CDFF and 300-microm thick microcosm dental plaques were grown over their exposed surfaces. The biofilms were maintained with a mucin-containing artificial saliva for up to 8 weeks. Cylinders were aseptically removed from the CDFF (at 1, 2, 4, & 8 weeks) and surface-decontaminated with validated protocols prior to splitting and sampling of apposing amalgam and dentine surfaces. Scanning electron microscopy (SEM) was used to ascertain the position and structure of the bacterial aggregates. Bacterial viability was determined by vital staining of the bacteria in situ. RESULTS: At all sampling times, SEM showed cocci, rods and filaments on both amalgam and dentine surfaces; some originated as cascades from the surface biofilm and extended into the tooth/restoration microspace. Vital staining showed the majority of bacteria from both dentine and amalgam surfaces to be viable. CONCLUSION: This preliminary investigation showed that the CDFF may be a valuable tool for the in vitro study of the dynamics of microbial microleakage around dental restorations.

Animals↗

The effects of surface roughness and type of denture acrylic on biofilm formation by Streptococcus oralis in a constant depth film fermentor.

AIMS: To investigate the effects of surface roughness and type of denture acrylic on the early development of a Streptococcus oralis biofilm in a constant depth film fermentor (CDFF). METHODS AND RESULTS: Streptococcus oralis was incubated with acrylic of known surface roughness in the CDFF. Adherent Strep. oralis were enumerated by viable counting. Cold-cure acrylic was rougher (P < 0.01) than heat-cure acrylic after polishing with abrasive paper of any given grit-grade. Heat-cure acrylic was colonized by fewer (P < 0.001) bacteria than cold-cure acrylic at any given surface roughness. The number of bacteria adhering to heat-cure and cold-cure acrylic increased linearly with mean surface roughness after 2 h incubation, the increase being greater (P < 0.001) for the cold-cure compared with the heat-cure acrylic. However, after 4 h incubation, surface roughness appeared to have no effect on the number of adherent bacteria. CONCLUSION: The type of acrylic used, and its roughness, affect the early stages of biofilm formation by Strep. oralis. SIGNIFICANCE AND IMPACT OF THE STUDY: Choosing an appropriate type of smooth acrylic could lead to reduced biofilm formation in vivo.

Biofilms↗