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Biomedical subjects

R L Williams

Publications and source records attributed to R L Williams.

At least 37 records · Page 2Linked to original sources
PubMed2002

Effects of plasma treated PET and PTFE on expression of adhesion molecules by human endothelial cells in vitro.

The aim of this study was to evaluate the expression of adhesion molecules on the surface of human endothelial cells in response to the systematic variation in materials properties by the ammonia plasma modification of polyethylene terephthalate (PET) and polytetrafluorethylene (PTFE). These adhesion molecules act as mediators of cell adhesion, play a role in the modulation of cell adhesion on biomaterials and therefore condition the response of tissues to implants. First and second passage human umbilical vein endothelial cells (HUVECs) were cultured on plasma treated and untreated PET and PTFE. HUVECs grown on polystyrene tissue culture coverslips and HUVECs stimulated with tumour necrosis factor (TNF-alpha) were used as controls. After 1 day and 7 days, the expression of adhesion molecules platelet endothelial cell adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1), Integrin alphavbeta3, vascular cell adhesion molecule-1 (VCAM-1), E-selectin, P-selectin and L-selectin were evaluated using flow cytometry and immunohistochemistry. There was a slight increase in positive cell numbers expressing the adhesion molecules ICAM-1 and VCAM-1 on plasma treated PET and PTFE. A significant increase in E-selectin positive cells on untreated PTFE was demonstrated after 7 days. Stimulation with TNF-alpha demonstrated a significant increase in the proportion of ICAM-1. VCAM-1 and E-selectin positive cells. Almost all cells expressed PECAM-1 and integrin alphavbeta3, on both materials and controls but did not express P- and L-selectin on any surface. When second passage cells were used, the expression of the adhesion molecules ICAM-1 and VCAM-1 was markedly increased on all surfaces but not with TNF-alpha. These significant differences were not observed in other adhesion molecules. These results were supported by immunohistochemical studies. The effects of plasma treated PET and PTFE on cell adhesion and proliferation was also studied. There was a 1.3-fold increase in cell numbers adhered on ammonia plasma treated PET compared to untreated PET and a 5.5-fold increase in cell numbers on treated PTFE compared to untreated PTFE after 1 day. This is significantly different when analysed statistically. After 7 days, cell number increased significantly on all surfaces compared to 1 day, except for untreated PTFE which conversely reduced by 41%. Cell number on the surface of untreated PET was no different to treated PET on days 1 and 7 when second passage cells were used. The study has shown that the plasma treatment of PET and PTFE with ammonia improves the adhesion and growth of endothelial cells and slightly upregulates the expression of adhesion molecules. This surface modification should promote colonisation of an artificial vascular prosthesis by endothelial cells and make it less vulnerable to immune system cells of the recipient. In addition, it should be considered which passage of cells is used due to the different adhesion features of different passages of HUVECs on untreated PET.

Biocompatible Materials↗
PubMed2002

Expression of leukocyte-endothelial cell adhesion molecules on monocyte adhesion to human endothelial cells on plasma treated PET and PTFE in vitro.

We used a coculture model to evaluate the inflammatory potential of ammonia gas plasma modified PET and PTFE by flow cytometry and immunohistochemistry. In these studies, human endothelial cells from umbilical cord (HUVEC) and promonocytic U937 cells were used. HUVECs grown on polystyrene tissue culture coverslips and HUVECs stimulated with tumour necrosis factor (TNF-alpha) were used as controls. U937 adhesion to endothelium on each surface was evaluated at day 1 and day 7. To further investigate the role of leukocyte-endothelial cell adhesion molecules (CAMs) in cell-to-cell interaction on material surfaces, the expression of the leukocyte-endothelial CAMs: ICAM-1, VCAM-1, PECAM-1, and E-selectin on HUVECs were evaluated after U937 cell adhesion. The results demonstrated that plasma treated PET (T-PET) and treated PTFE (T-PTFE) did not increase U937 cell adhesion compared to the negative control. Maximal adhesion of U937 cells to HUVEC was observed on TNF-alpha stimulated endothelium with significant differences between day 1 and day 7, which is consistent with our prior observation that T-PET and T-PTFE did not cause HUVECs to increase the expression of adhesion molecules. After U937 cell adhesion, the expression of ICAM-1 and VCAM-1 of HUVECs were not different on T-PET and T-PTFE compared with the negative control. However, the expression of E-selectin was reduced on day 1, but not on day 7. The effects of plasma treated PET and PTFE on HUVEC adhesion and proliferation were also studied. On day 1 there were slight increases in the growth of HUVECs on both of T-PET and T-PTFE but this was not statistically significant. On day 7, the cell number increased significantly on the surfaces compared to the negative control. The results demonstrate that the plasma treatment of PET and PTFE with ammonia improves the adhesion and growth of endothelial cells and these surfaces do not exhibit a direct inflammatory effect in terms of monocyte adhesion and expression of leukocyte-endothelial CAMs. The monocyte adhesion to endothelial cells on surfaces can be used as a tool for the evaluation of material surface modification and further to study the mechanisms of cell-to-cell interactions in response to surfaces.

Biocompatible Materials↗
PubMed2001

Tyrosine residues in phospholipase Cgamma 2 essential for the enzyme function in B-cell signaling.

Phospholipase Cgamma (PLCgamma) isoforms are regulated through activation of tyrosine kinase-linked receptors. The importance of growth factor-stimulated phosphorylation of specific tyrosine residues has been documented for PLCgamma1; however, despite the critical importance of PLCgamma2 in B-cell signal transduction, neither the tyrosine kinase(s) that directly phosphorylate PLCgamma2 nor the sites in PLCgamma2 that become phosphorylated after stimulation are known. By measuring the ability of human PLCgamma2 to restore calcium responses to the B-cell receptor stimulation or oxidative stress in a B-cell line (DT40) deficient in PLCgamma2, we have demonstrated that two tyrosine residues, Tyr(753) and Tyr(759), were important for the PLCgamma2 signaling function. Furthermore, the double mutation Y753F/Y759F in PLCgamma2 resulted in a loss of tyrosine phosphorylation in stimulated DT40 cells. Of the two kinases that previously have been proposed to phosphorylate PLCgamma2, Btk, and Syk, purified Btk had much greater ability to phosphorylate recombinant PLCgamma2 in vitro, whereas Syk efficiently phosphorylated adapter protein BLNK. Using purified proteins to analyze the formation of complexes, we suggest that function of Syk is to phosphorylate BLNK, providing binding sites for PLCgamma2. Further analysis of PLCgamma2 tyrosine residues phosphorylated by Btk and several kinases from the Src family has suggested multiple sites of phosphorylation and, in the context of a peptide incorporating residues Tyr(753) and Tyr(759), shown preferential phosphorylation of Tyr(753).

Agammaglobulinaemia Tyrosine Kinase↗
PubMed2001

Biomonitoring of persons exposed to insecticides used in residences.

Pesticides used indoors inevitably result in some unintentional and unavoidable exposures of residents. Measured dosages of residents are well below toxic levels. Exposures (microg/kg-day) are substantially less and occur over a longer time than suggested by unvalidated estimates derived from previous extreme, conservative default assumptions based solely on environmental residues. Human chlorpyrifos exposures were monitored following three different types of applications: fogger, broadcast, and crack-and-crevice. Persistence of total residue on carpet was substantially greater than the persistence of transferable residue (microg/cm(2)). Low-level (microg/kg) exposures of family members persisted for periods of weeks to a month after pesticide use. Although few children who resided with their parents in pest-protected homes have been monitored, they eliminated more biomarker than their parents on a kg body weight-day basis when absorbed dosages (microg/kg-day) were derived from spot urine specimens corrected for volume by an age-specific creatinine correction. Ultimately environmental residues may become useful elements of predictive residential exposure models, but their potential contribution to indirect exposure assessments must include careful determination of residue availability for contact transfer to clothing or skin and biological validation. When environmental data from monitoring studies reported here were used to estimate residential exposure according to Residential Exposure Assessment Standard Operating Procedures (SAP meeting, 1997), measured exposures were substantially less than assessments. Experimental and situational monitoring of exposed persons is essential for meaningful and responsible predictive resident exposure model building.

Administration, Cutaneous↗
PubMed2001

The crystal structure of the PX domain from p40(phox) bound to phosphatidylinositol 3-phosphate.

More than 50 human proteins with a wide range of functions have a 120 residue phosphoinositide binding module known as the PX domain. The 1.7 A X-ray crystal structure of the PX domain from the p40(phox) subunit of NADPH oxidase bound to PtdIns(3)P shows that the PX domain embraces the 3-phosphate on one side of a water-filled, positively charged pocket and reveals how 3-phosphoinositide specificity is achieved. A chronic granulomatous disease (CGD)-associated mutation in the p47(phox) PX domain that abrogates PtdIns(3)P binding maps to a conserved Arg that does not directly interact with the phosphoinositide but instead appears to stabilize a critical lipid binding loop. The SH3 domain present in the full-length protein does not affect soluble PtdIns(3)P binding to the p40(phox) PX domain.

Amino Acid Sequence↗
PubMed2001

Can you do a community assessment without talking to the community?

Conventionally, it has been accepted that an accurate understanding of community views on health topics can only come directly from community members. Yet, even as the need for this data has been increased by managed care, the methods of gathering it from community members remain costly and impractical for most busy practices or communities. This case study was conducted to determine whether well-informed health professionals can accurately and less expensively convey community views on health topics. In a low-income urban community, using a standard set of open-ended questions, focus groups and telephone and mail surveys were used to gather qualitative data from community residents and patients. Extended interviews and key informant surveys were used to gather similar data from health professionals. Data obtained from both sets of respondents were compared for content and logistics of collection. Overall, responses from the two groups had similar content but differing emphases. Community residents tended to emphasize socioeconomic determinants of health and everyday life concerns, while health care workers tended to emphasize the process of care. However, these perspectives were shared across the groups, as was an emphasis on the need for education with regard to community health concerns. The most striking difference between the groups was the community resources each group identified. As expected, costs for the health care worker approaches were less expensive. Findings from this case study suggest limited situations in which health care workers can adequately convey community views. In other situations, the different perspectives of each group can be complementary. Regardless of their role in qualitative data gathering, there remain important roles for community members in planning and decision-making regarding their health care.

Adult↗
PubMed2001

Variability in the bioavailability of phenytoin capsules in males and females.

PURPOSE: To determine inter-lot and intra-subject variability in the bioavailability of the 100 mg extended phenytoin sodium capsules. In addition, to determine the effect of gender and menstrual cycle on phenytoin bioavailability. METHODS: Three different lots of extended phenytoin sodium capsules were given to 12 healthy male and 12 healthy female subjects in a crossover fashion. One of the lots was also given a second time to each subject. Plasma phenytoin was determined, using an HPLC assay, in samples collected over a 73-hr period after each dose. RESULTS: The mean Cmax for the four administrations ranged from 1.71-1.79 microg/ml and mean AUC(0-infinity) values from ranged 53.0-54.1 microg*hr/ml. The elimination half-life was 3 hr shorter, and the AUC(0-infinity) adjusted for the mg/kg dose was 30% lower for females. Average bioequivalence was demonstrated between the three lots for both Cmax and AUC(0-infinity) based on the BE limit of 80-125%. Further, all confidence intervals of AUC(0-infinity) fell within the limit of 90-111%. There were no differences in the confidence limits for Cmax and AUC(0-infinity) determined separately for males and females. Also, there was no difference in the mean Cmax or AUC(0-infinity) for females when analyzed as a function of the week of their menstrual cycle. Individual bioequivalence was demonstrated between three lots of phenytoin using the constant-scaled method, but not the reference-scaled method. CONCLUSIONS: There was very little difference in the bioavailability of the three lots of phenytoin. Females exhibited a lower AUC(0-infinity) than males after adjustment of dose for body weight, but their inclusion in the study did not affect the assessment of bioequivalence. When dose was not adjusted for body weight, no difference in AUC(0-infinity) was seen between males and females.

Adult↗
PubMed2001

Neural network analysis of the prediction of cancer recurrence following debulking laparotomy and chemotherapy in stages III and IV ovarian cancer.

An artificial neural network (ANN) has been developed to predict the presence or absence of cancer following debulking laparotomy and chemotherapy in patients with stages III and IV ovarian cancer. The presence or absence of a residual gross tumor or microscopic disease was determined by a second-look laparotomy. The ANN was trained and tested using detailed operative findings and related surgical procedures associated with the debulking surgery. The ANN predictive results were compared with linear and logistic regression. The ANN significantly outperformed both logistic and linear regression analyses, but additional cases are needed to validate the network.

Female↗
PubMed2001

The influence of bracket type on the force delivery of Ni-Ti archwires.

This study investigated the force delivery of an 0.014 inch nickel-titanium (Ni-Ti) archwire used in combination with a range of commercially available bracket systems, and using a model based on an 'ideal' mandibular archform. The model aimed to replicate the clinical interbracket span. The force delivery was measured at four different sites on an archwire for one batch of 10 nickel titanium archwires from one manufacturer, using one bracket/archwire combination. The four sites represented the lateral incisor, canine, second premolar and first molar positions. Force delivery was also measured for a further four different bracket designs at four different sites on the archwire using five fresh wires of the same archwire type. The wires were loaded with an M5 Nene Universal testing machine. The results demonstrate that the peak and plateau force, both of which are clinically important, are dependent on several factors of the archwire/bracket combination. The results showed that 20 per cent of the batch of 10 wires behaved differently by delivering a higher peak force. There was a statistically significant difference (P < 0.05) between the four bracket/archwire combinations for the peak forces delivered, but there was very little difference between the four bracket/archwire unloading force delivery values. The wires delivered a predictable force on the unloading curves, but self-ligating brackets may not develop sufficient strain within the wire to take full advantage of the superelastic effect of Ni-Ti wires.

Dental Stress Analysis↗
PubMed2001

Race and preventive services delivery among black patients and white patients seen in primary care.

BACKGROUND: Numerous studies have documented racial disparities in delivery of health care treatment services, but there is little information to determine whether similar disparities exist in the delivery of preventive services. OBJECTIVE: To determine if disparities exist in preventive service delivery to non-Hispanic white patients and black patients in primary care. RESEARCH DESIGN: Multimethod study using direct observation of patient encounters, medical record review, and patient exit questionnaire. SUBJECTS: Four thousand three hundred thirteen outpatients presenting to 138 family physicians. MEASURES: Delivery of 15 screening, 24 health-habit counseling and 11 immunization services recommended by the US Preventive Services Task Force. RESULTS: Using multilevel linear regression analysis, no significant racial differences were found in rates of delivery of screening services or immunizations. However, black patients were more likely to receive preventive health-habit counseling (mean percent of patients up-to-date on all recommended counseling services, adjusted for covariates: 11.6% for black patients, 9.5% for whites, P = 0.003). CONCLUSIONS: Black patients able to access primary care receive preventive services at rates equal to or greater than white patients. This suggests that efforts to increase delivery of preventive care in black patients need to focus on access to primary care.

Adolescent↗
PubMed2001

Relationship of deep white matter hyperintensities and apolipoprotein E genotype to depressive symptoms in older adults without clinical depression.

OBJECTIVE: This study examined whether evidence of cerebrovascular disease in the form of magnetic resonance imaging (MRI) signal hyperintensities in white matter was associated with depressive symptoms in a high-functioning group of normal elderly volunteers. METHOD: Ninety-two community-dwelling elderly individuals participating in a study of white matter hyperintensities (WMHs) in normal aging whose apolipoprotein E (APOE) genotype had been determined completed the Geriatric Depression Scale and received an MRI scan. Univariate analyses of variance were used to examine the relationship between depressive symptoms and the location of WMHs (in deep white matter versus in periventricular white matter) and to determine whether WMHs were more likely to be associated with symptoms of impaired motivation and concentration or with mood symptoms. The effect on depressive symptoms of the interaction between severity of cerebrovascular disease as evidenced by WMHs and APOE genotype was also examined. RESULTS: Hyperintensities in the deep white matter, but not in the periventricular white matter, were associated with depressive symptoms, especially symptoms of impaired motivation, concentration, and decision making. The relationship between deep WMHs and depressive symptoms was especially strong in individuals carrying the APOE-4 allele. CONCLUSIONS: The pattern of depressive symptoms associated with WMHs in this study was similar to the pattern described in the literature as characterizing "vascular" depression in older persons with major depression. The results suggest that cerebrovascular disease may also underlie the depressive symptoms often found in older individuals who are not clinically depressed.

Aged↗
PubMed2001

Selective lengthening of the proximal flexor tendon in the management of acquired claw toes.

We report the management of the acquired claw-toe deformity in ten adults. Each patient developed a varying number of claw toes at a mean interval of six months after the time of injury. There was clinical evidence of an acute compartment syndrome in one case. The clawing occurred at the start of heel-rise in the stance phase of gait. At this stage the patients complained of increasing pain and pressure on the tips of the toes. The deformities were corrected by lengthening flexor hallucis longus and flexor digitorum longus alone or in combination. The presence of variable intertendinous digitations between the tendons of flexor hallucis longus and flexor digitorum longus means that in some cases release of flexor hallucis longus alone may correct clawing of lesser toes.

Adult↗
PubMed2001

Measures of exposure versus measures of rate and extent of absorption.

Regulatory assessment of bioavailability and bioequivalence in the US frequently relies on measures of rate and extent of absorption. Rate of absorption is not only difficult to measure but also bears little clinical relevance. This paper proposes that measures of bioavailability and bioequivalence for drugs that achieve their therapeutic effects after entry into the systemic circulation are best expressed in terms of early [partial area under the concentration-time curve (AUC)], peak plasma or serum drug concentration and total AUC exposure for a plasma or serum concentration-time profile. With suitable documentation, these systemic exposure measures can be related to efficacy and tolerability outcomes. The early measure is recommended for an immediate release drug product where a better control of drug absorption is needed, for example to ensure rapid onset of a therapeutic effect or to avoid an adverse reaction from a fast input rate. The 3 systemic exposure measures for bioavailability and bioequivalence studies can provide critical links between product quality and clinical outcome and thereby reduce the current emphasis on rate of absorption.

Absorption↗
PubMed2001

Use of capillary electrophoresis to quantitate carbamylated hemoglobin concentrations in dogs with renal failure.

OBJECTIVE: To evaluate quantification of the amount of carbamylated hemoglobin (CarbHb), using capillary electrophoresis (CE) and a new dynamic capillary coating system to separate hemoglobin derivatives, and to assess the use of CarbHb amounts to evaluate long-term urea exposure and differential diagnoses of azotemia in dogs. ANIMALS: 8 dogs with renal failure, 2 dogs with diabetes mellitus, and 7 control dogs. PROCEDURE: Optimal analytic conditions for separation of CarbHb and other hemoglobin derivatives in blood samples obtained from dogs were determined, using a commercial analysis system developed for the detection of glycohemoglobin Hb A1c (GlycHb) in human blood samples. Relative content of hemoglobin derivatives in blood from 10 dogs with renal failure or endocrine diseases were compared with values for 7 dogs without renal or endocrine diseases. RESULTS: Satisfactory resolution of hemoglobin derivatives was obtained, which permitted identification and quantitation of the amount of CarbHb as a percentage of the total amount of hemoglobin. Normal or increased amounts of GlycHb did not interfere with CarbHb analysis. Dogs with chronic renal failure had considerably higher peak amounts of CarbHb than dogs with acute renal failure, a dog with chronic renal failure that was treated by use of hemodialysis, or dogs without renal disease. CONCLUSIONS AND CLINICAL RELEVANCE: Amounts of CarbHb in blood samples obtained from dogs can be readily quantified by use of capillary electrophoresis. Assessment of the amount of CarbHb can be used to facilitate evaluation of the cause of azotemia in dogs.

Animals↗