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Biomedical subjects

J M Anderson

Publications and source records attributed to J M Anderson.

At least 109 records · Page 6Linked to original sources
PubMed1998

Blood and tissue compatibility of modified polyester: thrombosis, inflammation, and healing.

Poly(ethylene terephthalate) (PET) has been reported in literature to be moderately inflammatory and thrombogenic. To moderate the inflammatory response, PET fabric was surface modified by either Fluoropassiv fluoropolymer (FC), or an RGD-containing peptide (RGD). Samples were subsequently autoclave sterilized and implanted subcutaneously in Sprague Dawley rats for 2 to 4 weeks. Retrieved samples were evaluated histopathologically for indications of material toxicity and healing. Minimal acute or chronic inflammation was associated with the fabrics after 2 and 4 week implant duration. However, fibroblast proliferation into FC modified fabric (PET/FC) was less than that into unmodified (PET) and RGD modified fabric (PET/RGD) after 4 weeks, suggesting that FC modification of PET may inhibit excessive tissue growth. Additional samples of modified and unmodified fabrics were placed in stainless steel mesh cages, which were then implanted subcutaneously for 4 weeks. Cellular exudate was extracted weekly and cell concentrations within the exudate measured. Total leukocyte count (TLC) (reflective of local inflammation) at 1 week for PET/RGD was greater than that for PET/FC and PET. TLCs after 4 week implant decreased for all sample groups. In a separate experiment, PET vascular grafts surface modified by either FC or RGD were contacted 1 h with blood using the baboon arteriovenous (AV) shunt model of thrombosis in both the presence and absence of heparin. Accumulation of 111In labeled platelets (reflective of thrombus accumulation) upon grafts was less in the presence of heparin (effect significant at p = 1.2 x 10(-6), two-way ANOVA). Accumulation (in the presence of heparin) upon PET/RGD was less (p = 0.19), and upon PET/FC significantly less (p = 0.016) than that upon the unmodified PET control, suggesting that FC modification of PET may inhibit thrombus accumulation.

Animals↗
PubMed1998

Subconjunctival biocompatibility of a viscous bioerodable poly(ortho ester).

The biocompatibility of a viscous poly(ortho ester) (POE) intended for prolonged intraocular drug delivery was studied. This hydrophobic and bioerodable carrier was subconjunctivally injected in rabbits and evaluated both clinically and histologically. To assess the cause of the triggered transient acute inflammatory reaction, the two monomers, the intermediate and final degradation products, and the local toxicity of different solvents used during the polymer preparation were tested. Since the two initial monomers and the intermediate degradation products induced only moderate inflammation, the main acute inflammatory reaction is attributed to the formation of an acidic by-product which has been monitored in vitro by measuring the progressive decrease of the environmental pH. The influence of the sterilization procedure on tissue biocompatibility was established by comparing two polymers of similar molecular weight: one after gamma-sterilization, and an aseptically synthesized one. The biocompatibility was significantly improved by avoiding irradiation of the polymer.

Animals↗
PubMed1998

Human monocyte/macrophage adhesion, macrophage motility, and IL-4-induced foreign body giant cell formation on silane-modified surfaces in vitro. Student Research Award in the Master's Degree Candidate Category, 24th Annual Meeting of the Society for Biomaterials, San Diego, CA, April 22-26, 1998.

A cytokine-based, in vitro model of foreign body giant cell (FBGC) formation was utilized to examine the effect of biomaterial surface chemistry on the adhesion, motility, and fusion of monocytes and macrophages. Human monocytes were cultured for 10 days on 14 different silane-modified glass surfaces, during which time the cells assumed the macrophage phenotype. The adhesion of monocytes and macrophages during the culture period decreased by an average of approximately 50%, with the majority of cell loss observed during days 1-3. Most important, the adhesion of monocytes and macrophages was surface independent except for two surfaces containing terminal methyl groups, which decreased adhesion levels. Interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were added to the medium to induce FBGC formation and enhance macrophage adhesion, respectively. Surprisingly, GM-CSF decreased long-term monocyte/macrophage adhesion. IL-4-induced FBGC density was strongly influenced by the surface carbon content, as determined by X-ray photoelectron spectroscopy (XPS). In contrast, contact angle and surface energy displayed no correlation with FBGC formation. The motility of adherent macrophages, as measured by time-lapse confocal microscopy, was not affected significantly by differences in surface chemistry or the addition of cytokines. The surface dependence of FBGC formation is hypothesized to be the result of varying levels of silane-derived surface carbon.

Adult↗
PubMed1998

In vitro and in vivo degradation of poly(propylene fumarate-co-ethylene glycol) hydrogels.

The degradation of poly(propylene fumarate-co-ethylene glycol) hydrogels was examined in vitro in phosphate-buffered saline at pH 7.4 and in vivo in a subcutaneous rat model. These hydrogels have potential application as biodegradable, injectable cardiovascular stents, and, as such, their mass loss, dimensional changes, mechanical properties, morphology, and biocompatibility over a 12-week time course were evaluated. Three formulations were fabricated: one base formulation consisting of 25% (w/w) PEG, molecular weight 4,600; one high weight percent PEG formulation with 50% (w/w) PEG; and one high molecular weight PEG formulation, molecular weight 10,500. All three formulations showed significant weight loss (between 40 and 60%) on the first day due to leaching of the uncrosslinked fraction. Further weight loss was observed only for the low weight percent PEG copolymers in the in vivo case, and a slight increase in volume was observed due to degradative swelling. The mechanical properties of the P(PF-co-EG) hydrogels decreased significantly in the first 3 weeks, showing the biphasic pattern typical of bulk degradation. In vitro, the hydrogels showed at least a 20% retention of their initial ultimate tensile stress after 3 weeks. The dynamic mechanical properties showed similar retention, with the in vivo mechanical properties differing from the in vitro properties only after 6 weeks of degradation. Differences in PEG molecular weight appeared to have little effect, but increasing the weight percent PEG decreased the rate of degradation both in vitro and in vivo. The morphology of the copolymer films, based on scanning electron microscopy observation, was not significantly different either among the three formulations or over the time course of the study, suggesting there were no macroscopic structural changes during this time period. The P(PF-co-EG) hydrogels demonstrated good initial biocompatibility, showing responses characteristic of biomaterial implants.

Animals↗
PubMed1998

Evaluation of expanded polytetrafluoroethylene arteriovenous access grafts onto which microvessel-derived cells were transplanted to "improve" graft performance: preliminary results.

The purpose of this study was to implement and evaluate a clinical protocol for following longitudinally the luminal responses of microvessel cell seeded expanded polytetrafluoroethylene (ePTFE) vascular grafts implanted for hemodialysis access. Half of the patients enrolled in the study were randomized to receive grafts that were "seeded" with transplanted microvessel cells derived from autologous subcutaneous fat; the other half of the patients received nonseeded grafts. The patients agreed to scheduled biopsies of their grafts at three postoperative times. All biopsy samples were evaluated by routine histologic and electron microscopy techniques. Three men and six women were enrolled in the study. All operative procedures were tolerated well. However, only two of the nine patients agreed to 1-year postimplantation biopsies; one of these patients had been randomized to receive a "nonseeded" ePTFE graft and one randomized to receive a "seeded" graft. The "seeded" graft at 3 months showed endothelial cells on the luminal surface as well as some intimal thickening. By 20 months, the same "seeded" graft showed significant concentric intimal thickening and by 24 months, this "seeded" graft thrombosed. The "nonseeded" graft at 16 months had irregular areas of intimal thickening which were quite patchy in nature. The flow contacting surface of the "nonseeded" graft remained thin. The intima of the "seeded" graft was twice as thick as that of the "nonseeded" graft. The methodologies implemented in the study design were appropriate. Biopsy samples were obtained without complication and were easily processed for analysis. Patient compliance with the biopsy protocol was problematic however. The study was terminated because of the development of significant concentric intimal hyperplasia in a "seeded" graft.

Arteriovenous Shunt, Surgical↗
PubMed1998

Speaking of illness: issues of first generation Canadian women--implications for patient education and counseling.

Based upon my research with first generation Canadian women who have come from Asia, I discuss the issues in women's lives that influence how they manage a chronic illness. I argue that women's relations with health care providers, the organization of the health care system, and structural constraints, especially for those women in the lower echelons of the labour force, profoundly influence the illness experience. Taking this, as the starting point, I proceed to examine the implications for education and counseling. I propose a model for counseling that begins with a critical examination, by health professionals, of their own 'culture of health', and that acknowledges the knowledge and wisdom of women. I suggest that a pedagogical relationship between health care professionals and women can be a site for the development of transformative knowledge and the empowerment of women.

Asia↗
PubMed1998

Crystal structure of the hCASK PDZ domain reveals the structural basis of class II PDZ domain target recognition.

PDZ domain containing proteins assist formation of cell-cell junctions and localization of membrane protein receptors and ion channels. PDZ domains interact with the C-terminal residues of a particular target membrane protein. Based on their binding specificities and sequence homologies, PDZ domains fall into two classes. The first crystal structure of a class II PDZ domain, that of hCASK, has been solved by multi-wavelength anomalous dispersion phasing. Complex formation with the C-terminus of a neighboring non-crystallographically related PDZ domain reveals interactions between hCASK and its ligand. Class II PDZ domains differ from class I domains by formation of a second hydrophobic binding pocket. The C-terminal carboxylate binding loop of the PDZ domain is structurally conserved in both classes suggesting a generalized carboxylate binding motif (h-Gly-h) where h is a hydrophobic residue.

Amino Acid Sequence↗
PubMed1998

The effect of semantic and emotional context on written recall for verbal language in high functioning adults with autism spectrum disorder.

OBJECTIVE: Several deficits have been proposed to account for cognitive impairment in autism including an inability to comprehend the perspectives of others ("theory of mind"), an inability to process emotional information, and difficulty drawing together diverse information in context ("central coherence"). Because context (central coherence) and emotion can influence memory, a study was designed to show if autism spectrum disorder was associated with impaired utilisation of context and emotion in recall; and if impairments in theory of mind processing would influence recall in autism spectrum disorder. METHODS: Ten high functioning subjects with autism spectrum disorder and 13 age and IQ matched controls were tested using recall tests. In the first coherence memory test, subjects listened to a series of word lists that were in varying degrees of syntactic and semantic (coherent) order and were asked to recall the words. In the second coherence memory test, subjects listened to stories consisting of sentences that were, or were not, in logical (coherent) order. In the emotional memory test, the subjects listened to sentences that were highly emotional or non-emotional. In the theory of mind test, the subjects listened to stories requiring varying levels of understanding of the perspectives of others. RESULTS: There were no significant differences between groups in recall of coherent versus incoherent word lists, nor was there a significant difference between groups in recall of coherent versus incoherent stories. However, the control subjects recalled more of the emotional than non-emotional sentences, whereas the autism spectrum disorder group did not show such a difference. No significant difference existed in recall of stories requiring varying levels of understanding of the perspectives of others among subjects with autism spectrum disorder, and subjects with autism spectrum disorder did not differ from control subjects in the influence of theory of mind content on story recall. CONCLUSION: The study shows that memory in high functioning adults with autism spectrum disorder is facilitated by emotional content to a lesser degree than it is facilitated by coherence. Therefore, impairments in emotional processing cannot be considered as simply an effect of the "weak central coherence" theory in autism spectrum disorder. Whereas the reasons for this emotional deficit are unknown, evidence of abnormalities of the limbic structures in autism spectrum disorder may provide an anatomical explanation.

Adult↗
PubMed1998

Molecular architecture of tight junctions.

The tight junction creates a regulated barrier in the paracellular pathway and, together with the actin-rich adherens junction, forms a functional unit called the apical junction complex. A growing number of tight junction-associated proteins have been identified, but functions are defined for only a few. The intercellular barrier is formed by rows of the transmembrane protein occludin, which is bound on the cytoplasmic surface to ZO-1 and ZO-2. These proteins are members of the membrane-associated guanylate kinase (MAGUK) protein family and are likely to have both structural and signaling roles. Junctional plaque proteins without known functions include cingulin, p130, and 7H6; single reports describe ZA-1TJ and symplekin. Many cellular signaling pathways affect assembly and sealing of junctions. Transducing proteins, which localize within the junction, include both heterotrimeric and rho-related GTP-binding proteins, PKC-zeta and nonreceptor tyrosine kinases. Control of perijunctional actin may be the unifying mechanism for regulating paracellular permeability.

Amino Acid Sequence↗
PubMed1998

Impaired stimulus-driven orienting of attention and preserved goal-directed orienting of attention in unilateral visual neglect.

Neglect patients do not respond to stimuli presented on the side of space contralateral to the side of their brain lesions, indicating deficits to attentional or representational mechanisms. We describe a patient who shows a left neglect in normal reading and line bisection but an intact ability to locate the left end of the stimulus. Further tests showed that his seemingly intact ability to search into the "neglected" side was due to his ability to use local elements of the stimulus as cues in his serial search for the left end. The patient's left neglect was significantly reduced after he located the left end of the stimulus. In contrast, his neglect was not reduced by making the stimulus on the neglected side physically more salient. These results suggest that his neglect is due largely to an impairment of the mechanism mediating automatic, stimulus-driven orienting of attention. In contrast, the controlled goal-directed attentional search is largely preserved and can be used to alleviate neglect.

Apraxias↗
PubMed1997

Leukocyte-biomaterial interactions in the presence of Staphylococcus epidermidis: flow cytometric evaluation of leukocyte activation.

The adhesion of bacteria on a biomaterial surface is believed to be the first step in the development of biomaterial-related infection. The goal of this study was to investigate the mechanisms that permit adherent bacteria to persist on the surface of an implanted cardiovascular biomaterial. We hypothesized that circulating leukocytes are unable to adhere to the biomaterial surface under physiologic shear stress conditions, and this prevents them from interacting with adherent bacteria. To address this hypothesis, we investigated the adhesion profiles of Staphylococcus epidermidis and polymorphonuclear leukocytes (PMN), incubated under controlled shear stress conditions with the test biomaterial. We found that bacteria could adhere on the biomaterial surface, even when their concentration in the test medium was as low as 10(3) cfu/mL. At this concentration, the bacteria did not induce significant complement activation. PMN adhesion on the biomaterial surface was sensitive to shear stress and minimal at shear stress > 10 dynes/cm2. Low concentrations of bacteria could induce a significant increase in the expression of PMN adhesion molecules CD11b and CD11c. We conclude that the presence of bacteria induces PMN activation but does not increase PMN adhesion on biomaterial surfaces under physiologic shear stress conditions. This could be a major mechanism that protects adherent bacteria from PMN antibacterial activity.

Bacterial Adhesion↗
PubMed1997

The effect of strain state on the biostability of a poly(etherurethane urea) elastomer.

The effect of deformation state on degradation of a PEUU without added stabilizers was examined in an oxidative environment that simulates the in vivo biodegradation of the polymer. Polymer tubes were stressed uniaxially and biaxially over glass mandrels and treated in 20% hydrogen peroxide/0.1 M cobalt chloride solution for 12 days at 37 degrees C. The amount of degradation was determined from the ATR-FTIR peak height of the amorphous aliphatic ether absorbance at 1110 cm-1. If a uniaxial stress was applied, degradation was inhibited and the amount of surface ether remaining after treatment increased linearly with strain. If the stress was biaxial, the amount of degradation was not reduced unless the strain was greater than 200%. Decreased degradation correlated with the amount of soft-segment orientation. The decreased degradation rate was attributed to compaction of the polyether phase by orientation, which resulted in lower permeability to oxidative agents, particularly oxygen. Macroscopic damage was confined to a thin peeling surface layer if the stress was uniaxial. In comparison, biaxially stressed PEUU ruptured.

Biocompatible Materials↗
PubMed1997

Interleukin-13 induces human monocyte/macrophage fusion and macrophage mannose receptor expression.

Inasmuch as we recently demonstrated that IL-4 is a strong inducer of monocyte/macrophage fusion and IL-13 has been observed to mimic many of the biologic effects of IL-4, the ability of IL-13 to promote human macrophage fusion in vitro was tested and compared with IL-4-mediated fusion. IL-13 induced the fusion of monocyte-derived macrophages as potently as IL-4 under identical culture conditions, and resulted in foreign body-type giant cell formation. At optimal concentrations of cytokine added, statistically equal numbers of macrophages participated in IL-13- and IL-4-induced fusion (66.1 +/- 4.6% and 63.9 +/- 4.4%, respectively). However, the effects of IL-13 and IL-4 were not additive or synergistic, and the maximum fusion obtained when both IL-4 and IL-13 were added was 63.8 +/- 3.6%. Only anti-human IL-13 Abs inhibited IL-13-induced foreign body giant cell formation; the fusion-inducing effects of IL-13 continued to be observed in the presence of neutralizing Abs to IL-4 and several other anti-cytokine Abs, including Abs against IFN-gamma, granulocyte-macrophage CSF, IL-3, and TNF-alpha. IL-13 also significantly enhanced the fluorescence intensity detected by anti-human macrophage mannose receptor Abs, indicating that IL-13, like IL-4, up-regulates expression of the receptor that may be an essential participant in macrophage fusion. The results of this study demonstrate that IL-13, like IL-4, is a potent human macrophage fusion factor, and suggest that although IL-13 acts independently of IL-4 to promote foreign body giant cell formation, it may trigger a common mechanism for macrophage fusion.

Cell Fusion↗
PubMed1997

Comparison of two antioxidants for poly(etherurethane urea) in an accelerated in vitro biodegradation system.

Vitamin E (+/-alpha-tocopherol) was recently investigated as an antioxidant for implanted poly(etherurethane urea) (PEUU) elastomers. In that work, vitamin E prevented chemical degradation of biaxially strained PEUU up to 5 weeks implantation, and prevented pitting and cracking of the PEUU surface for the duration of the 10-week cage implant study. The promising results of the in vivo studies motivated a detailed comparison of vitamin E with Santowhite, the standard antioxidant used in PEUU elastomers. To evaluate vitamin E and Santowhite as antioxidants in PEUU, an accelerated in vitro treatment system was used that mimics the in vivo degradation of PEUUs. Vitamin E was even more effective than Santowhite in preventing pitting and cracking to the biaxially strained PEUU elastomers. The inhibition of ether oxidation was greater with vitamin E than with Santowhite when compared by equivalent concentrations and molar concentrations, respectively. It is hypothesized that the increased effectiveness of vitamin E in this system, compared to Santowhite, is due to differences in antioxidant mechanism(s). Vitamin E is more efficient in preventing PEUU oxidation than Santowhite because its phenoxy radical is more stable and it can terminate more than one chain per vitamin E molecule.

Antioxidants↗
PubMed1997

Role of oxygen in biodegradation of poly(etherurethane urea) elastomers.

It is generally accepted that biodegradation of poly(etheruethane urea) (PEUU) involves oxidation of the polyether segments on the surface where leukocytes are adhered. The influence of dissolved oxygen, which is known to control oxidation of polymers in more traditional environments, was explored in this study. Specimens treated in vitro with hydrogen peroxide-cobalt chloride for 12 days exhibited a brittle, degraded surface layer about 10 microm thick. Attenuated total reflectance-Fourier transform infrared spectroscopy of the surface revealed that the ether absorbance at 1110 cm(-1) gradually decreased with in vitro treatment time to 30% of its initial value after 12 days. In contrast, 6 days in vitro followed by 6 days in air produced a decrease to 12% of the initial volume. Therefore, removing a specimen from the in vitro solution after 6 days and exposing it to air for the remainder of the 12 days actually resulted in more oxidation than leaving it in the in vitro solution for the entire 12 days. These results suggest that PEUU degrades by an autooxidation mechanism sustained by oxygen. By successfully modeling the depth of the surface degraded layer with a diffusion-reaction model, it was demonstrated that PEUU biodegradation is controlled by diffusion of oxygen into the polymer.

Biocompatible Materials↗