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Biomedical subjects

G W Taylor

Publications and source records attributed to G W Taylor.

At least 19 recordsLinked to original sources
PubMed2005

Reparative properties of a commercial fish protein hydrolysate preparation.

BACKGROUND: A partially hydrolysed and dried product of pacific whiting fish is currently marketed as a health food supplement to support "intestinal health". However, there has been only limited scientific study regarding its true biological activity. AIMS: We therefore tested its efficacy in a variety of models of epithelial injury and repair. METHODS: Effects on proliferation were determined using [(3)H] thymidine incorporation into epithelial rat intestinal RIE-1 and human colonic HT29 cells. Effects on restitution (cell migration) were analysed using wounded HT29 monolayers and its ability to influence gastric injury analysed using a rat indomethacin restraint model. Partial characterisation of bioactive agents was performed using mass spectroscopy, high pressure liquid chromatography, and gas chromatography. RESULTS: Both cell proliferation and cell migration were increased by about threefold when added at 1 mg/ml (p<0.01). Gastric injury was reduced by 59% when gavaged at 25 mg/ml (p<0.05), results similar to using the potent cytoprotective agent epidermal growth factor at 12.5 mug/ml. The vast majority of biological activity was soluble in ethanol, with glutamine in its single, di-, and tripeptide forms probably accounting for approximately 40% of the total bioactivity seen. Fatty acid constituents may also have contributed to cell migratory activity. CONCLUSIONS: Fish protein hydrolysate possesses biological activity when analysed in a variety of models of injury and repair and could provide a novel inexpensive approach for the prevention and treatment of the injurious effects of non-steroidal anti-inflammatory drugs and other ulcerative conditions of the bowel. Further studies appear justified.

Animals↗
PubMed2005

Smokeless tobacco and severe active periodontal disease, NHANES III.

Whereas smoking is a major risk factor for periodontal disease, the role of smokeless tobacco is unclear. The purpose of this US population-based study of 12,932 adults participating in the Third National Health and Nutrition Examination Survey was to evaluate the association between smokeless tobacco use and severe active periodontal disease. Univariable and multivariable logistic regression modeling quantified the associations between tobacco use and severe active periodontal disease. All adults and never-smokers who currently used smokeless tobacco were twice as likely to have severe active periodontal disease at any site [respective odds ratios (OR(Adj)) and 95% confidence intervals: OR(Adj) = 2.1; 1.2-3.7 and OR(Adj) = 2.1; 1.0-4.4] or restricted to any interproximal site [respective OR(Adj) = 2.1; 1.0-4.2 and OR(Adj) = 2.3; 0.9-6.3], simultaneously adjusted for smoking, age, race, gender, diabetes, and having a dental visit in the past year. These results indicate that smokeless tobacco may also be an important risk factor for severe active periodontal disease.

Adolescent↗
PubMed2005

Prevalence and trends in periodontitis in the USA: the [corrected] NHANES, 1988 to 2000.

Trends in periodontal diseases in the USA have been documented for years. However, the results have been mixed, mostly due to different periodontal assessment protocols. This study examined change in the prevalence of periodontitis between the NHANES III and the NHANES 1999-2000, and differences in the prevalence of periodontitis among racial/ethnic groups in the USA. Analysis was limited to non-Hispanic black, non-Hispanic white, and Mexican-American adults aged 18+ yrs in the NHANES III (n=12,088) or the NHANES 1999-2000 (n=3214). The prevalences of periodontitis for the NHANES III and the NHANES 1999-2000 were 7.3% and 4.2%, respectively. In multivariable analyses, blacks were 1.88 times (95%CI: 1.42, 2.50) more likely to have periodontitis than whites surveyed in the NHANES III. However, the odds of periodontitis for blacks and Mexican-Americans did not differ from those for whites surveyed in the NHANES 1999-2000. Our findings indicate that the prevalence of periodontitis has decreased between the NHANES III and the NHANES 1999-2000 for all racial/ethnic groups in the USA.

Adult↗
PubMed2004

Plasma pharmacokinetics and metabolism of the histone deacetylase inhibitor trichostatin a after intraperitoneal administration to mice.

Trichostatin A is a potent and specific histone deacetylase inhibitor with promising antitumor activity in preclinical models. Plasma pharmacokinetics of trichostatin A were studied following single-dose intraperitoneal administration of 80 mg/kg (high dose) or 0.5 mg/kg (low dose) to female BALB/c mice. Plasma trichostatin A concentrations were quantified by high performance liquid chromatography (HPLC)-UV assay (high dose) or by HPLC-multiple reaction monitoring assay (low dose). Trichostatin A was rapidly absorbed from the peritoneum and detectable in plasma within 2 min. Cmax of 40 microg/ml and 8 ng/ml occurred within 5 min, followed by rapid exponential decay in plasma trichostatin A concentration with t1/2 of 6.3 min and 9.6 min (high and low doses, respectively). Phase I metabolites at the high dose were identified by simultaneous UV and positive ion electrospray mass spectrometry. Trichostatin A underwent extensive metabolism: primary metabolic pathways were N-demethylation, reduction of the hydroxamic acid to the corresponding trichostatin A amide, and oxidative deamination to trichostatic acid. N-Monomethyl trichostatin A amide was the major plasma metabolite. No didemethylated compounds were identified. Trichostatic acid underwent further biotransformation: reduction and beta-oxidation of the carboxylic acid, with or without N-demethylation, resulted in formation of dihydro trichostatic acid and dinor dihydro trichostatic acids. HPLC fractions corresponding to trichostatin A and N-demethylated trichostatin A exhibited histone deacetylase-inhibitory activity; no other fractions were biologically active. We conclude that trichostatin A is rapidly and extensively metabolized in vivo following intraperitoneal administration to mice, and N-demethylation does not compromise histone deacetylase-inhibitory activity.

Animals↗
PubMed2002

Targeted pharmacological depletion of serum amyloid P component for treatment of human amyloidosis.

The normal plasma protein serum amyloid P component (SAP) binds to fibrils in all types of amyloid deposits, and contributes to the pathogenesis of amyloidosis. In order to intervene in this process we have developed a drug, R-1-[6-[R-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid, that is a competitive inhibitor of SAP binding to amyloid fibrils. This palindromic compound also crosslinks and dimerizes SAP molecules, leading to their very rapid clearance by the liver, and thus produces a marked depletion of circulating human SAP. This mechanism of drug action potently removes SAP from human amyloid deposits in the tissues and may provide a new therapeutic approach to both systemic amyloidosis and diseases associated with local amyloid, including Alzheimer's disease and type 2 diabetes.

Amyloidosis↗
PubMed2001

The transmembrane protein occludin of epithelial tight junctions is a functional target for serine peptidases from faecal pellets of Dermatophagoides pteronyssinus.

There have been only a few studies of how allergens cross the airway epithelium to cause allergic sensitization. House dust mite fecal pellets (HDMFP) contain several proteolytic enzymes. Group 1 allergens are cysteine peptidases, whilst those of groups 3, 6 and 9 have catalytic sites indicative of enzymes that mechanistically behave as serine peptidases. We have previously shown that the group 1 allergen Der p 1 leads to cleavage of tight junctions (TJs), allowing allergen delivery to antigen presenting cells. In this study we determined whether HDMFP serine peptidases similarly compromise the airway epithelium by attacking TJs, desmosomes and adherens junctions. Experiments were performed in monolayers of MDCK, Calu-3 or 16HBE14o-epithelial cells. Cell junction morphology was examined by 2-photon molecular excitation microscopy and digital image analysis. Barrier function was measured as mannitol permeability. Cleavage of cell adhesion proteins was studied by immunoblotting and mass spectrometry. HDMFP serine peptidases led to a progressive cleavage of TJs and increased epithelial permeability. Desmosomal puncta became more concentrated. Cleavage of TJs involved proteolysis of the TJ proteins, occludin and ZO-1. This was associated with activation of intracellular proteolysis of ZO-1. In contrast to occludin, E-cadherin of adherens junctions was cleaved less extensively. Although Calu-3 and 16HBE14o-cells expressed tethered ligand receptors for serine peptidases, these were not responsible for transducing the changes in TJs. HDMFP serine peptidases cause cleavage of TJs. This study identifies a second general class of HDM peptidase capable of increasing epithelial permeability and thereby creating conditions that would favour transepithelial delivery of allergens.

Amino Acid Sequence↗
PubMed2001

Aspiration pneumonia: dental and oral risk factors in an older veteran population.

OBJECTIVES: To investigate the importance of medical and dental factors in aspiration pneumonia in an older veteran population. DESIGN: Prospective enrollment of subjects with retrospective analysis of data. SETTING: Department of Veterans Affairs outpatient clinic, inpatient ward, and nursing home. PARTICIPANTS: 358 veterans age 55 and older; 50 subjects with aspiration pneumonia. MEASUREMENTS: Demographic and medical data; functional status; health-related behaviors; dental care utilization; personal oral hygiene; comprehensive dental examination; salivary assays including IgA antibodies; and cultures of saliva, throat, and dental plaques. RESULTS: Two logistic regression models produced estimates of significant risk factors. One model using dentate patients included: requiring help with feeding (odds ratio (OR) = 13.9), chronic obstructive pulmonary disease (COPD) (OR = 4.7), diabetes mellitus (OR = 3.5), number of decayed teeth (OR = 1.2), number of functional dental units (OR = 1.2), presence of important organisms for decay, Streptococcus sobrinus in saliva (OR = 6.2), and periodontal disease, Porphyromonous gingivalis in dental plaque (OR = 4.2), and Staphylococcus aureus presence in saliva (OR = 7.4). The second model, containing both dentate and edentulous patients included: requiring help with feeding (OR = 4.7), COPD (OR = 2.5), diabetes mellitus (OR = 1.7), and presence of S. aureus in saliva (OR = 8.3). CONCLUSION: This study supports the significance of oral and dental factors while controlling for established medical risk factors in aspiration pneumonia incidence.

Activities of Daily Living↗
PubMed2001

A longitudinal analysis of salivary flow in control subjects and older adults with type 2 diabetes.

OBJECTIVE: Many diabetics complain of xerostomia, a condition that can affect oral health, nutritional status, and diet selection. This study's purposes were (1) to investigate the effect on salivary flow of type 2 diabetes and change in glycemic control in a group of older adults over time and (2) to compare flow rates with subjective complaints of xerostomia. STUDY DESIGN: A total of 39 older adults, 24 with type 2 diabetes and 15 who were nondiabetic (controls), aged 54-90 years, participated in a 1-year follow-up study. Diabetic status was determined by means of glycosylated hemoglobin (HbA1c) levels and 2-hour glucose tolerance tests. Poor glycemic control was defined as HbA1c > 9%. Unstimulated whole, unstimulated parotid, and stimulated parotid saliva flow rates were measured for all subjects by a single examiner at baseline and 1 year later. Each subject completed a standardized xerostomia questionnaire at every visit. RESULTS: Age, sex, and duration of diabetes did not adversely affect salivary flow rates. Subjects with poorly controlled diabetes had significantly lower stimulated parotid saliva flow rates at both visits. There were no significant changes in flow rates over time on the basis of diabetic status or glycemic control. Subjects with diabetes reported significantly more complaints of thirst but not of xerostomia at 1 year. CONCLUSIONS: These results suggest that older adults with poorly controlled diabetes may have impaired salivary flow in comparison with subjects with better controlled diabetes and nondiabetic subjects, yet they may not have concomitant xerostomic complaints. There were no significant changes in salivary flow rates or glycemic control over the 1-year period.

Aged↗
PubMed2001

Determinants of variable response to statin treatment in patients with refractory familial hypercholesterolemia.

Interindividual variability in low density lipoprotein (LDL) cholesterol (LDL-C) response during treatment with statins is well documented but poorly understood. To investigate potential metabolic and genetic determinants of statin responsiveness, 19 patients with refractory heterozygous familial hypercholesterolemia were sequentially treated with placebo, atorvastatin (10 mg/d), bile acid sequestrant, and the 2 combined, each for 4 weeks. Levels of LDL-C, mevalonic acid (MVA), 7-alpha-OH-4-cholesten-3-one, and leukocyte LDL receptor and hydroxymethylglutaryl coenzyme A reductase mRNA were determined after each treatment period. Atorvastatin (10 mg/d) reduced LDL-C by an overall mean of 32.5%. Above-average responders (LDL-C -39.5%) had higher basal MVA levels (34.4+/-6.1 micromol/L) than did below-average responders (LDL-C -23.6%, P<0.02; basal MVA 26.3+/-6.1 micromol/L, P<0.01). Fewer good responders compared with the poor responders had an apolipoprotein E4 allele (3 of 11 versus 6 of 8, respectively; P<0.05). There were no baseline differences between them in 7-alpha-OH-4-cholesten-3-one, hydroxymethylglutaryl coenzyme A reductase mRNA, or LDL receptor mRNA, but the latter increased in the good responders on combination therapy (P<0.05). Severe mutations were not more common in poor than in good responders. We conclude that poor responders to statins have a low basal rate of cholesterol synthesis that may be secondary to a genetically determined increase in cholesterol absorption, possibly mediated by apolipoprotein E4. If so, statin responsiveness could be enhanced by reducing dietary cholesterol intake or inhibiting absorption.

Anticholesteremic Agents↗
PubMed2001

Bidirectional interrelationships between diabetes and periodontal diseases: an epidemiologic perspective.

This review evaluates evidence for a bidirectional relationship between diabetes and periodontal diseases. A comprehensive Medline search of the post-1960 English language literature was employed to identify primary research reports of relationships between diabetes and periodontal diseases. Reports included in the review on the adverse effects of diabetes on periodontal health (DM-->PD) were restricted to those comparing periodontal health in subjects with and without diabetes. Review of adverse affects of periodontal infection on glycemic control included reports of periodontal treatment studies and follow-up observational studies in which changes in glycemic control could be assessed. Observational studies reporting DM-->PD provided consistent evidence of greater prevalence, severity, extent, or progression of at least one manifestation of periodontal diseases in the large majority of reports (supportive evidence in 44/48 total reviewed; 37/41 cross-sectional and 7/7 cohort). Additionally, there were no studies reviewed with superior design features to refute this association. Treatment studies provided direct evidence to support periodontal infection having an adverse, yet modifiable, effect on glycemic control. However, not all investigations reported an improvement in glycemic control after periodontal treatment. Additional evidence to support the effect of severe periodontitis on increased risk for poorer glycemic control comes from 2 follow-up observational studies. The evidence reviewed supports viewing the relationship between diabetes and periodontal diseases as bidirectional. Further rigorous, systematic study is warranted to establish that treating periodontal infections can be influential in contributing to glycemic control management and possibly to the reduction of the burden of complications of diabetes mellitus.

Age Factors↗
PubMed2001

Exploring interrelationships between diabetes and periodontal disease in African Americans.

Population-based data on interrelationships between diabetes and periodontal diseases among African Americans are limited. This article is an overview of our knowledge regarding the bidirectional relationship between diabetes and periodontal diseases and a descriptive analysis of data from the Third National Health and Nutrition Examination Survey (NHANES III), focusing on the diabetes-periodontal diseases interrelationship in African Americans. Results of the analysis are consistent with the current body of evidence supporting a bidirectional relationship between diabetes and periodontal diseases and indicate generally poorer periodontal health and glycemic control among African Americans. The results also indicate significantly lower dental care use in dentate African Americans with diabetes than in the US non-Hispanic white population with diabetes.

Adolescent↗
PubMed2000

Pathological effects of extensive radiofrequency energy applications in the pulmonary veins in dogs.

INTRODUCTION: The long-term complications of catheter ablation within the pulmonary veins are unknown. The development of pulmonary vein stenosis has recently been described after catheter ablation to treat either chronic or paroxysmal atrial fibrillation. The purpose of this study was to examine the pathological and hemodynamic effects of radiofrequency (RF) energy application within the pulmonary veins. METHODS AND RESULTS: Right heart and transseptal catheterization were performed in 9 anesthetized mongrel dogs. The pulmonary vein ostia were cannulated and pulmonary venous pressure was measured before RF energy application in up to 4 separate pulmonary veins. Animals were euthanized at intervals of 2 to 4 weeks (n=3), 6 to 8 weeks (n=3), or 10 to 14 weeks (n=3) after ablation. Repeat catheterization before euthanasia demonstrated statistically significant differences in pulmonary capillary wedge pressure, cardiac output, pulmonary vascular resistance, and systemic vascular resistance (P<0.05) compared with the baseline. Luminal narrowing was observed in 22 of 33 pulmonary veins to which RF energy was applied. Of these, 7 were totally occluded, 7 had severe stenosis, and 8 were only minimally narrowed. Histological examination revealed intimal proliferation with organizing thrombus, necrotic myocardium in various stages of collagen replacement, endovascular contraction, and a proliferation of elastic lamina. CONCLUSIONS: Applications of RF current within the pulmonary veins may result in pulmonary vein narrowing or complete occlusion. These observations should be considered in treatment of arrhythmias originating within the pulmonary veins.

Animals↗
PubMed2000

Recognition and management of Kawasaki disease.

Kawasaki disease is the leading cause of acquired heart disease in children in the developed world, with coronary artery aneurysms occurring in up to 25% of untreated cases. The mean annual incidence of Kawasaki disease across Canada is about 13 per 100,000 children less than 5 years of age, based on hospital discharge data from 1990 to 1995. The cause remains unknown, and the diagnosis is based on the same clinical criteria used to describe the disease over 30 years ago. However, nonspecific clinical features, evolving presentations and atypical or incomplete presentations make early diagnosis and timely treatment difficult. Delays in diagnosis and treatment, which occur more frequently in older children, are associated with an increased risk of coronary artery aneurysms. Hence, high diagnostic suspicion and prompt referral are required to reduce the rate of cardiac complications.

Adolescent↗
PubMed2000

Analysis of N(alpha)-methylhistamine by gas chromatography-mass spectrometry.

A gas chromatography-electron capture mass spectrometry assay has been developed for the histamine H3 receptor agonist, N(alpha)-methylhistamine (N(alpha)-MH). The assay is linear from 50 pg-10 ng, with a limit of detection of 50 pg/ml for gastric juice and plasma, and 50 pg/sample for bacteria (10(7)-10(8) CFU) and gastric tissue (5-10 mg wet weight). The limits of quantification are 100 pg/ml for gastric juice (%RSD=1.4) and plasma (%RSD=9.4), and 100 pg/sample for bacteria (%RSD=3.9) and tissue (%RSD=5.8). N(alpha)-MH was not present in human plasma, but low levels (1.4 ng/ml and 0.4 ng/ml) were detected in two samples of human gastric juice obtained from patients infected with Helicobacter pylori.

Gas Chromatography-Mass Spectrometry↗
PubMed2000

CGS 21680, dibutyryl cyclic AMP and rolipram attenuate the pro-inflammatory interactions of the Pseudomonas aeruginosa -derived pigment, 1-hydroxyphenazine, with human neutrophils.

The effects of the intracellular adenosine 3':5' cyclic monophosphate (cAMP)-elevating agents, CGS 21680 (0.01- 1 microM) and rolipram (0.01-1 microM), as well as those of dibutyryl cAMP (0. 05-4 mM) on the pro-inflammatory interactions of the P. aeruginosa -derived pigment, 1-hydroxyphenazine (1-hp, 3.1 and 12.5 microM), with human neutrophils have been investigated in vitro. Ca(2+)fluxes in FMLP-activated neutrophils were measured using a fura-2/AM spectrofluorimetric procedure, while a colourimetric method was used to measure release of the primary granule enzyme, elastase, from the cells. Treatment with 1-hp resulted in delayed clearance of Ca(2+)from the cytosol of N -formyl- L -methionyl- L -leucyl- L -phenylalanine (FMLP, 1 microM)-activated neutrophils and increased release of elastase. All 3 test agents caused dose-related antagonism of 1-hp-mediated potentiation of elastase release from activated neutrophils, which was associated with restoration of Ca(2+)homeostasis. These observations demonstrate the potential of cAMP-elevating agents, acting on Ca(2+)clearance mechanisms in activated neutrophils, to attenuate the potentially harmful pro-inflammatory effects of 1-hp.

Adenosine↗
PubMed2000

N alpha-methylhistamine: association with Helicobacter pylori infection in humans and effects on gastric acid secretion.

Infection with the bacterium Helicobacter pylori is associated with altered gastric acid secretion and gastrointestinal disease. Recent work has suggested that N alpha-methylhistamine, produced by the bacterium and acting on histamine receptors in gastric tissue, might be involved. Gastric juice and tissue biopsies from infected patients have been analysed for the presence of N alpha-methylhistamine using a specific and sensitive assay based on gas chromatography mass spectrometry. N alpha-Methylhistamine was detected in five of seven samples of gastric juice from infected patients (5-180 pmol/ml) but was absent in nine uninfected subjects. The compound was not found in fundic and antral biopsies from both subject groups. Helicobacter pylori, cultured on agar and in broth with and without added histamine, was found not to produce detectable levels of N alpha-methylhistamine. Instillation of this compound at 10(-5) mol/l into the gastric lumen produced a significant increase in acid secretion in vivo while plasma gastrin concentration remained unchanged. N alpha-Methylhistamine in gastric juice appears therefore to be associated with infection, although this product is not generated directly by the bacterium. The concentrations found are below those required to affect acid secretion or gastrin production in vivo, although higher local concentrations may exist around a site of infection.

Gas Chromatography-Mass Spectrometry↗
PubMed2000

Salivary function and glycemic control in older persons with diabetes.

OBJECTIVE: There is no consensus on the possible association between diabetes and salivary dysfunction in older persons with diabetes. This study's purpose was to investigate the effect of diabetes and glycemic control on salivary function in an older population. STUDY DESIGN: Twenty nine persons with type 2 diabetes and 23 nondiabetic control subjects participated (age range, 54-90 years). Diabetic status was determined by a glycosylated hemoglobin (HbA(1c)) test and a 2-hour glucose tolerance test. Poor glycemic control was defined as HbA(1c) >9%. Unstimulated whole saliva, unstimulated parotid, and stimulated parotid flow rates were measured, and subjects completed a standardized xerostomia questionnaire. RESULTS: Persons with poorly controlled diabetes had lower (P =.01) stimulated parotid flow rates than persons with well-controlled diabetes and nondiabetic control subjects. There were no significant differences in xerostomic complaints based on diabetic or glycemic control status or salivary flow rates. CONCLUSIONS: These results provide some evidence that poorly controlled diabetes may be associated with salivary dysfunction in older adults who have no concomitant complaints of xerostomia.

Aged↗