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Biomedical subjects

R M Watson

Publications and source records attributed to R M Watson.

At least 19 recordsLinked to original sources
PubMed2001

Conformational changes in pediocin AcH upon vesicle binding and approximation of the membrane-bound structure in detergent micelles.

Pediocin AcH is a 44-residue antimicrobial peptide with bactericidal potency against Gram-positive bacteria such as Listeria. It belongs to a family of bacteriocins that, when membrane-associated, is predicted to contain beta-sheet and alpha-helical regions. All bacteriocins in this family have a conserved N-terminal disulfide bond. An additional C-terminal disulfide bond in pediocin AcH is thought to confer enhanced potency and broader specificity range against sensitive bacteria. The C-terminal disulfide bond may also affect the conformation of the C-terminus. The secondary structures of pediocin AcH in aqueous solution and vesicles from susceptible cells, as well as the ability of trifluoroethanol (TFE) and detergent systems to induce secondary structures like those induced in vesicles, were studied by circular dichroism (CD) spectroscopy. Like related peptides, pediocin AcH was highly unordered in aqueous solution, 56%. However, it also contained 20% beta-strand and 15% beta-turn structures. Upon complete binding to vesicles, 32% alpha-helical structure formed, the unordered structure decreased to 32%, and the beta-strand and beta-turn structures remained largely unchanged. Thus, a betaalpha domain structure formed in vesicles. The helical structure likely forces the C-terminal tail to loop back on the helix so that the C24-C44 disulfide bond can form. Detergent micelles were superior to TFE in their ability to induce secondary structural fractions in pediocin AcH comparable to those observed in vesicles. This demonstrates the importance of a hydrocarbon-water interface to pediocin AcH structure induction and suggests that it is preferable to use detergent micelles as solvents in NMR studies of pediocin AcH structure.

Amino Acid Sequence↗
PubMed2001

Inhaled leukotriene E(4), but not leukotriene D(4), increased airway inflammatory cells in subjects with atopic asthma.

Allergen-induced late airway responses are associated with increased numbers of airway eosinophils and basophils. The purpose of this study was to compare and contrast the effects of inhaled cysteinyl leukotrienes LTD(4) and LTE(4), which are released during allergen- induced airway responses, and allergen, on airway inflammatory cells. Fifteen subjects with atopic, mild asthma inhaled diluent, LTD(4), LTE(4), and allergen. Spirometry was performed for 7 h, and sputum inflammatory cells were measured before, 7 h, and 24 h after challenges. The maximum early percent fall in FEV(1) was 23.6 +/- 1.4%, 21.6 +/- 2.3%, 29.3 +/- 2.4%, and 4.0 +/- 1.1% after LTD(4), LTE(4), allergen, and diluent, respectively. Only inhaled LTE(4) and allergen significantly increased sputum eosinophils at 7 h and 24 h, and sputum basophils at 7 h. Six additional subjects underwent airway biopsies 4 h after inhalation. There were significantly more eosinophils in the lamina propria after inhalation of LTE(4) compared with LTD(4) and diluent (p < 0.05). These results suggest cysteinyl leukotrienes play a role in eosinophil migration into the airways in allergic asthma, and for the same degree of bronchoconstriction, inhaled LTE(4) causes more tissue and airway eosinophilia than LTD(4).

Administration, Inhalation↗
PubMed2001

Dose-dependent effects of inhaled mometasone furoate on airway function and inflammation after allergen inhalation challenge.

Comparisons of the potency of different inhaled corticosteroids, delivery devices, and treatment regimens in the management of asthma can only be made when outcome measurements display a dose-dependent effect. These outcomes have been difficult to identify. In this study, we compared in a randomized, double-blind, crossover design, the effects of 6 d treatment with placebo and three doses (50, 100, and 400 microg, twice daily) of mometasone furoate delivered by dry powder inhaler (MF-DPI) on responses after allergen inhalation challenge. Twelve mild asthmatic subjects with dual responses after allergen inhalation were studied. Outcome measurements included early and late asthmatic responses, the change in methacholine airway responsiveness 24 h after challenge, and sputum eosinophilia measured 7 and 24 h after challenge. All three doses of MF-DPI demonstrated similar attenuation of early responses and allergen-induced airway hyperresponsiveness relative to placebo (p < 0.05). The late maximal %fall in FEV(1) after placebo treatment was 23.5% and was significantly reduced in a dose-dependent manner to 12.3%, 11.0%, and 5.9% for the 50-, 100-, and 400-microg twice-daily treatments (p = 0.007). The allergen-induced increase in sputum eosinophilia (x10(4) cells/ml) 24 h after challenge during placebo treatment was 60.2 and was significantly reduced to 24.0, 15.3, and 6.2 for the 50-, 100-, and 400-microg twice-daily treatments. MF-DPI is effective at attenuating allergen-induced early and late responses, airway hyperresponsiveness, and sputum eosinophilia, and dose-response effects exist for the attenuation of the late response.

Administration, Inhalation↗
PubMed2001

The contribution of imaging and digitised data to mandibular reconstruction and implant stabilised occlusal rehabilitation: a case report.

Different methods are recommended for the surgical reconstruction of the resected mandible. The advantages for implant stabilised prostheses in restoring the occlusion are recognised but few papers provide adequate data to identify the successful outcome of treatment. The literature is reviewed and the advantages of imaging together with the use of digitised data is highlighted by a case requiring rehabilitation with enhanced planning methods.

Bone Transplantation↗
PubMed2001

The reproducibility and sample size requirements of exercise-induced bronchoconstriction measurements.

Dry air exercise challenges are frequently used to screen medications that have potential utility in the management of exercise-induced bronchoconstriction (EIB). The purpose of this study was to determine the reproducibility of three outcome measurements made using such challenges, and sample size requirements for drug evaluation studies based on these outcomes. Forty adult subjects with asthma, who tested positively on a screening exercise challenge, were subjected to two further identical challenges, separated by 1 to >35 days. Outcome measurements included the maximum per cent fall in forced expiratory volume in one second (FEV1), after exercise (% fallmax), and the area under the per cent fall in FEV1/time curve for 30 min (AUC30) and 60 min (AUC60) after exercise. The reproducibility of these outcomes, as assessed by intraclass correlation coefficients was 0.72, 0.53 and 0.35 for % fallmax, AUC30 and AUC60 measurements, respectively. The sample size requirements to demonstrate an attenuation of EIB equivalent to a 50% reduction in % fallmax was 9, 14 and 19 subjects for the % fallmax, AUC30 and AUC60 responses, respectively (90% power). It is concluded that the maximum percentage fall in forced expiratory volume in one second has greater reproducibility and results in greater power in clinical trials than area under the curve measurements. Sample size calculation curves are provided which may be used in study design and interpretation of published studies.

Adult↗
PubMed2000

Comparison of platelet activation in unstable and stable angina pectoris and correlation with coronary angiographic findings.

We sought to investigate the relation between platelet activation and the angiographic evidence of ruptured plaque in patients presenting with unstable and stable angina pectoris. We prospectively enrolled 25 consecutive patients (5 women and 20 men, mean age 62 +/- 3 years), 17 with unstable angina and 8 with stable angina. Systemic venous blood samples were collected within 4 to 6 hours of admission for flow cytometry analysis. Activation-dependent epitope CD63 and glycoprotein IIb/IIIa on the platelet membrane were assayed. Fibrinogen levels were also measured. All patients with unstable angina underwent cardiac catheterization and had angiographic evidence of ruptured plaque. Of the patients with stable angina, 5 underwent coronary angiography with smooth noncomplex lesions and 3 had negative technetium-99m sestamibi stress tests. Patients with unstable angina were characterized by 39% higher levels of fibrinogen than patients with stable angina (423 +/- 304 vs 304 +/- 51 mg/dl, p = 0.004). The percentage of platelets positive for the activation-dependent epitope CD63 was 5 times higher in patients with unstable than stable angina (14.6 +/- 5.6% vs 2.75 +/- 1.6%, p = 0.0026). They also had a 15% higher expression of their glycoprotein IIb/IIIa (517 +/- 79 vs 449 +/- 50 mean fluorescence intensity, p = 0.038). Thus, this study establishes a direct relation between the morphology of ruptured plaque and platelet activation in patients with unstable angina. This may allow for further risk stratification. Patients with unstable complex lesions had a fivefold higher expression of the platelet activation epitope CD63 than patients with stable angina. Furthermore, they had 15% more glycoprotein IIb/IIIa aggregation sites expressed on their platelet membrane, thus indicating an intense thrombogenic potential.

Aged↗
PubMed2000

Transcript quantitation in total yeast cellular RNA using kinetic PCR.

Kinetically monitored, reverse transcriptase-initiated PCR (kinetic RT-PCR, kRT-PCR) is a novel application of kinetic PCR for high throughput transcript quantitation in total cellular RNA. The assay offers the simplicity and flexibility of an enzyme assay with distinct advantages over DNA microarray hybridization and SAGE technologies for certain applications. The reproducibility, sensitivity and accuracy of the kRT-PCR were assessed for yeast transcripts previously quantitated by a variety of methods including SAGE analysis. Changes in transcript levels between different genetic or physiological cell states were reproducibly quantitated with an accuracy of +/-20%. The assay was sufficiently sensitive to quantitate yeast transcripts over a range of more than five orders of magnitude, including low abundance transcripts encoding cell cycle and transcriptional regulators.

DNA Primers↗
PubMed2000

Healing of spontaneous coronary dissection in the context of glycoprotein IIB/IIIA inhibitor therapy: a case report.

Spontaneous coronary artery dissection is a rare cause of myocardial infarction. It is a condition with greater prevalence in young women, particularly in the peripartum or early postpartum period. It also has been described following intense physical exercise. The pathophysiologic characteristics remain unclear. Unlike atherosclerotic intimal dissection, the dissection plane lies within the media or between the media and adventitia. We describe a case of spontaneous coronary artery dissection in a 44-yr old menstruating woman with mitral valve prolapse, who experienced acute myocardial infarction after twisting and throwing a heavy piece of luggage. Coronary angiography showed coronary artery dissection in a left anterior descending coronary artery at the point of its emergence from its intramural course. An intimal plaque with 90-95% obstruction and reduced (TIMI I) flow was demonstrated. The patient was treated with continued glycoprotein IIb/IIIa inhibitor infusion. Angiographic resolution with return of prompt (TIMI III) flow was noted. Optimal management of spontaneous coronary artery dissection has not been established and may vary, depending upon the presence of intimal versus extramural compromise. Coronary artery bypass, stenting, and thrombolysis have been successful and also have failed, owing to extension of dissection. Our patient is the first reported patient to have received tirofiban therapy in the context of spontaneous coronary artery dissection. Medical therapy has been used most often, and angiographic resolution has been documented at 94 days, 7 mo, and 1 yr. We document the earliest case of spontaneous angiographic resolution-within 20 hr.

Adult↗
PubMed2000

Effects of once daily dosing with inhaled budesonide on airway hyperresponsiveness and airway inflammation following repeated low-dose allergen challenge in atopic asthmatics.

BACKGROUND: Repeated low-dose allergen challenge increases airway hyperresponsiveness and sputum eosinophils in atopic asthmatics. Inhaled corticosteroids attenuate the airway responses to high-dose allergen challenge, but have not been evaluated against repeated low dose challenge. OBJECTIVE: This study evaluates the effects of once daily treatments of two doses of inhaled budesonide on airway responses to repeated low-dose allergen challenge. METHODS: Eight atopic asthmatics with a dual airway responses to inhaled allergen were recruited into a randomized, double-blind crossover, placebo-controlled study. In the mornings of four consecutive days (day 1-day 4), subjects inhaled budesonide 100 microg, 400 microg, or placebo, 30 min before inhaling a concentration of allergen causing a 5% early fall in FEV1. Airway hyperresponsiveness to methacholine and sputum eosinophils were measured at baseline, on the afternoon of day 2, day 4, and 24 h after the last challenge. There was a 1-week washout between each of the three treatment periods. RESULTS: The repeated low-dose allergen challenge induced increases in the percentage sputum eosinophils from 2.0 +/- 0.7% at baseline to 16.6 +/- 7.1% on day 4 (P = 0.002), and this effect was reduced by once daily budesonide 100 microg to 5.6 +/- 1.8% (P = 0. 01) and by once daily budesonide 400 microg to 3.1 +/- 0.9% (P = 0. 004). Also, the allergen-induced methacholine airway hyperresponsiveness which occurred by day 4 (P = 0.03) of the repeated low dose challenge was inhibited by budesonide 400 microg (P = 0.017). CONCLUSION: Both budesonide 100 microg and 400 microg inhaled once daily significantly reduces allergen-induced sputum eosinophilia after repeated low dose challenge; however, only the higher dose also attenuates the allergen-induced airway hyperresponsiveness.

Adult↗
PubMed2000

Increased numbers of both airway basophils and mast cells in sputum after allergen inhalation challenge of atopic asthmatics.

Mast cells and basophils are metachromatic cells that participate in allergic inflammation. Allergen challenge to the airways of atopic asthmatic individuals increases levels of metachromatic cells, which may reflect an increase in mast cells, basophils, or both. We conducted a study to characterize the kinetics of basophil and mast cell recruitment to the airways of atopic asthmatic subjects after allergen inhalation challenge, using monoclonal antibodies specific for each type of cell. Of 19 subjects, 14 developed both early- and late-phase asthmatic responses (dual responders [DRs]), whereas five developed only early asthmatic responses (early responders [ERs]) after allergen inhalation. There was a significant increase in the number of sputum eosinophils (p < 0.002) and basophils (p < 0.002) at 7 h and 24 h after challenge in both ERs and DRs. There was also a significant increase in the number of activated eosinophils (p = 0. 00002) and mast cells (p = 0.009) in sputum at 7 h and 24 h after challenge in DRs, but not in ERs (p > 0.4). DRs had a significantly higher number of allergen-induced sputum basophils than did ERs (p < 0.01), and sputum basophils correlated significantly with airway hyperresponsiveness (AHR) to methacholine at 24 h after challenge (r = 0.66, p = 0.002). DRs tended to have higher allergen-induced basophil levels than did ERs, which may contribute to the observed AHR.

Adult↗
PubMed2000

Exercise-induced bronchoconstriction does not cause eosinophilic airway inflammation or airway hyperresponsiveness in subjects with asthma.

The cysteinyl leukotrienes (LT) C(4), D(4), and E(4) may partially mediate eosinophilic airway inflammation in patients with asthma. High- intensity exercise by patients with asthma can result in exercise- induced bronchoconstriction, partly due to leukotriene production, but it is still debated whether this causes airway inflammation. Ten subjects completed a randomized, controlled study to examine the effects of exercise-induced bronchoconstriction on airway inflammatory cells. Subjects completed exercise challenge and methacholine challenge in random order separated by 1 wk. Spirometry was measured for 2 h after challenges, and airway responsiveness was measured the day before and 24 h after each challenge. Blood and sputum samples were obtained before, and 2, 4, 7, and 24 h after each challenge for measurement of inflammatory cells. Nine of the subjects inhaled allergen at least 3 wk before or 1 wk after the study. Sputum samples were collected before, 7 h, and 24 h after challenge. The maximum percentage fall in FEV(1) was 21.3 +/- 1.5% after exercise, 29.9 +/- 1.5% after methacholine, and 28.9+/-2.7% after allergen. Exercise had no effect on airway responsiveness or inflammatory cells measured in blood or sputum, unlike allergen inhalation, which resulted in significant airway hyperresponsiveness and increases in sputum eosinophils (p < 0.05). This study demonstrates that exercise-induced bronchoconstriction does not cause eosinophilic airway inflammation in subjects with asthma who develop airway inflammation with the same degree of allergen-induced bronchoconstriction. We conclude that exercise-induced bronchoconstriction does not cause airway inflammation or airway hyperresponsiveness.

Adolescent↗
PubMed2000

The effects of inhaled budesonide on circulating eosinophil progenitors and their expression of cytokines after allergen challenge in subjects with atopic asthma.

Allergen inhalation by dual responder subjects with atopic asthma is associated with an increase in circulating eosinophil/basophil colony-forming units (Eo/B CFU) and granulocyte-macrophage colony- stimulating factor (GM-CSF) immunolocalization in Eo/B colony cells grown in vitro. The current study examined the effect of the inhaled corticosteroid, budesonide, on the number of allergen- induced circulating eosinophils and Eo/B CFU, and immunolocalization of GM-CSF and interleukin-5 (IL-5) in Eo/B colony cells grown in vitro. Sixteen subjects with mild atopic asthma were treated for either 7 or 8 d with 200 microg inhaled budesonide or placebo twice a day. Peripheral blood was collected before and 24 h after allergen inhalation challenge and nonadherent mononuclear cells (NAMC) were grown in methylcellulose culture. Eo/B CFU were enumerated after 14 d in culture, and prepared on slides for immunocytochemistry. Budesonide attenuated the allergen-induced increase in circulating eosinophils (4.0 +/- 0.4 x 10(5)/ml versus 6.5 +/- 0.7 x 10(5)/ml, p = 0.0001), circulating Eo/B CFU (12.4 +/- 2.3/10(6) NAMC versus 18.8 +/- 4.6/10(6) NAMC, p = 0.05), and immunolocalization of GM-CSF in Eo/B colony cells (11.8 +/- 1.9% positive versus 18.0 +/- 2.2%, p = 0.01) but not immunolocalization of IL-5 (7.9 +/- 1.4% versus 4.5 +/- 0.6%, p > 0.05). Inhaled budesonide attenuated the number of allergen-induced circulating eosinophils and their progenitors grown in the presence of GM-CSF, which may partially be a result of regulating eosinophil progenitor expression of the autocrine growth factor GM-CSF.

Administration, Inhalation↗
PubMed2000

The occlusal management of maxillary anterior single-unit implant-supported restorations.

This paper, with the aid of clinical examples, highlights some of the common occlusal problems that can be associated with maxillary anterior single-unit implant-supported restorations. The authors stress the importance of thorough pre-operative planning to identify any likely occlusal problems. This allows patients to be fully informed of the impact of any necessary clinical compromise and of the need for and nature of modifications to the natural dentition.

Adult↗
PubMed2000

Laser scanning of the ear identifying the shape and position in subjects with normal facial symmetry.

The objective of the present study was to discover if dimensional measurements of the ear could be determined with a laser scanning technique and whether or not the location of landmarks of the ear could be reliably measured with respect to those on the midline of the face. Computer-generated images were created from laser scans of 20 subjects. Dimensional measurements were made between landmarks on the ear and face. Differences between repeated dimensional measurements of the ear were very small, as were those measurements made between landmarks on the ear to the midline of the face. Differences between dimensions of the left and right ears were observed, but were of a small magnitude. The results suggest that the dimensions of the ear and its position with respect to landmarks in the midline of the face can be reliably measured on normal subjects and that laser scanning is a useful technique for planning and monitoring facial reconstruction of the ear.

Adolescent↗
PubMed2000

A comparison of the early postoperative care required by patients treated with single and two stage surgical techniques for the provision of Brånemark implant supported mandibular overdentures.

Patients who underwent a single stage surgical procedure to place two Brånemark implants to stabilise complete mandibular overdentures with bar attachments, required no more postoperative follow-up visits before definitive prosthesis construction than patients who had their implants placed at two separate surgical stages. However, the visits of the single stage group, occurred over a shorter time-scale and more attention was required to tighten or replace their healing abutments.

Aged↗
PubMed1999

Repeatability of allergen-induced airway inflammation.

BACKGROUND: Allergen inhalation challenge is a useful clinical model to investigate the effects of asthma therapies on allergen-induced airway responses; however, the repeatability of allergen-induced airway inflammation is not known. OBJECTIVE: The purpose of this study was to investigate the repeatability of allergen-induced increases in sputum eosinophils. This information will allow the prediction of the number of subjects required in studies evaluating asthma therapies. METHODS: Seventeen subjects completed 2 allergen challenges using the same dose of allergen, at least 3 weeks apart. Allergen-induced airway responses were measured for 7 hours after challenge. Differential cell counts from induced sputum were determined the day before and 7 and 24 hours after challenge; methacholine PC20 was measured the day before and 24 hours after challenge. RESULTS: The intraclass correlation coefficient for maximum percent late fall in FEV1 was 0.32 and for the area of the late response was 0.61. The sample size predicted to be necessary to observe 50% attenuation of the maximum percent late fall in FEV1 and the late area under the curve with a power of 0.95 was 9 subjects. The intraclass correlation coefficient for percent of allergen-induced sputum eosinophils was 0.60 at 7 hours and 0.53 at 24 hours after challenge. With a randomized cross-over study design, the sample size predicted to be necessary to observe 50% attenuation of allergen-induced percent of eosinophils with a power of 0.95 was 5 subjects. CONCLUSION: Allergen inhalation challenge with measurements of sputum eosinophils is a noninvasive and reliable method for evaluating the anti-inflammatory effects of asthma therapies.

Adult↗