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Biomedical subjects

S Ferguson

Publications and source records attributed to S Ferguson.

At least 19 recordsLinked to original sources
PubMed2001

Anti-Sm B cell differentiation in Ig transgenic MRL/Mp-lpr/lpr mice: altered differentiation and an accelerated response.

To determine the regulation of B cells specific for the ribonucleoprotein Sm, a target of the immune system in human and mouse lupus, we have generated mice carrying an anti-Sm H chain transgene (2-12H). Anti-Sm B cells in nonautoimmune 2-12H-transgenic (Tg) mice are functional, but, in the absence of immunization, circulating anti-Sm Ab levels are not different from those of non-Tg mice. In this report, we compare the regulation of anti-Sm B cells in nonautoimmune and autoimmune MRL/Mp-lpr/lpr (MRL/lpr) and bcl-2-22-Tg mice. Activation markers are elevated on splenic and peritoneal anti-Sm B cells of both nonautoimmune and autoimmune genetic backgrounds indicating Ag encounter. Although tolerance to Sm is maintained in 2-12H/bcl-2-22-Tg mice, it is lost in 2-12H-Tg MRL/lpr mice, as the transgene accelerates and increases the prevalence of the anti-Sm response. The 2-12H-Tg MRL/lpr mice have transitional anti-Sm B cells in the spleen similar to nonautoimmune mice. However, in contrast to nonautoimmune mice, there are few if any peritoneal anti-Sm B-1 cells. These data suggest that a defect in B-1 differentiation may be a factor in the loss of tolerance to Sm and provide insight into the low prevalence of the anti-Sm response in lupus.

Aging↗
PubMed2001

Cardiac performance in endurance-trained and moderately active young women.

PURPOSE: To compare the cardiac performance of endurance-trained (ET) and moderately active (MA) young women before exercise and throughout incremental work rates to maximum with particular interest in whether their stroke volume (SV) levels off at a submaximal work rate or increases to maximum. METHODS: Blood volume (BV), and exercise cardiac performance were examined in seven ET (VO2max = 64.3 +/- 2.0 mL.kg(-1).min(-1)) and seven MA (VO2max = 42.1 +/- 1.0 mL.kg(-1).min(-1)) women, aged 18-30 yr. Cardiac time intervals were measured at matched heart rates (HR). RESULTS: ET had a significantly larger BV than MA in both mL (ET = 5053 +/- 139, MA = 4327 +/- 202) and mL.kg(-1) (ET = 83.1 +/- 1.4, MA = 72.9 +/- 2.7). The SV of ET was significantly larger than the SV of MA throughout exercise, and the SV of ET increased progressively throughout incremental work rates to maximum. Although the SV of MA initially leveled off at a submaximal work rate, it underwent a secondary increase at very heavy work rates. Both diastolic filling rate (DFR) and left ventricular emptying rate (LVER) were significantly faster in ET compared with MA at HR of 150 bpm, 170 bpm and HRmax, and in both ET and MA, DFR was significantly faster than LVER at 170 bpm and HRmax. CONCLUSIONS: In young women, ET have a larger SV than MA due to an enhanced DFR and LVER, with the primary advantage being DFR (possibly due to their larger BV). In addition, the SV of ET increases progressively throughout incremental work rates to maximum with no plateau, whereas the SV of MA levels off through moderate to heavy work rates then undergoes a secondary increase at very heavy work rates.

Adolescent↗
PubMed2001

Effect of COX-2 inhibitor NS-398 on expression of PGE2 receptor subtypes in M-1 mouse CCD cells.

Our present study has investigated the effect of cyclooxygenase-2 (COX-2) inhibition on prostaglandin E2 (PGE2) receptor expression in M-1 cortical collecting duct cells and measured their response to PGE2. Using a semiquantitative titration analysis method, we show that following the addition of the COX-2-specific inhibitor NS-398, E-prostanoid receptor subtype (EP3 and EP4) mRNA expression was found to increase threefold each vs. the vehicle-treated control. We also observed that EP1 but not EP2 is expressed in M-1 cells and EP2 levels are not induced by NS-398. To determine the status of the PGE2 response on exposure to NS-398, we measured cAMP levels in cells after stimulation with varying concentrations of PGE2, then pretreated the cells with 10 microM NS-398 before PGE2 exposure and found a significant rise in the stimulatory effect of PGE2 on cAMP production. Finally, Western blot analysis of the levels of the EP4 receptor protein in control vs. NS-398-treated cells revealed an induction in protein levels in these cells, correlating with the induction in EP4 mRNA. We conclude that NS-398 upregulates the expression of EP3 and EP4 mRNA in M-1 cells. Also, EP4 protein levels are increased, resulting in an increased stimulation of cAMP production by PGE2.

Animals↗
PubMed2000

Where is the light field edge: perception of different operators on different surfaces.

On most radiotherapy treatment units, a light field indicates on the patient's skin where the treatment field will irradiate the patient. It was the aim of the present study to investigate the perception of the light field edge by different operators on different surfaces under different lighting conditions. Ten radiation therapists and physicists were asked to mark the light field edge of an 8 x 10-cm2 radiation field from a linear accelerator on prepacked radiographic film. Each operator marked the field 4 times each with the room light turned on and dimmed as usual for patient setup. Two operators marked the field on 5 different surfaces (film envelope, brown solid water, clear plastic used for the manufacturing of immobilization shells, black rubber, and Orfit patient immobilization material). The interoperator reproducibility (+/- 0.39 mm, ISD) was larger than the intraoperator reproducibility (+/- 0.27 mm). The light field was judged consistently to be 0.6 mm smaller in the light room than under dimmed light conditions and the physicists judged the field to be approximately 0.4 mm smaller compared to the radiation therapists' judgement. Compared to the yellow film wrapping, the light field on solid water, black rubber, and the clear plastic were judged to be 0.6 mm smaller by both operators. The same observation was made using a slotted block tray, which also gave the worst reproducibility of perceived field edges. While these systematic errors are relatively small and difficult to correct for, it appears to be important to be at least aware of them, in particular if the light field is used to junction radiation fields with steep penumbras, as commonly done in megavoltage treatments of head & neck and breast cancer.

Humans↗
PubMed2000

Pulmonary sequestration presenting as a prenatally detected suprarenal lesion in a neonate.

An echogenic suprarenal mass was detected antenatally in the fetus by routine ultrasound scan. Resection of the mass after delivery confirmed an extralobar pulmonary sequestration with features of a type II congenital cystic adenomatoid malformation of the lung. The lesion should be considered in all neonates presenting with a suprarenal or upper abdominal mass particularly when the mass has been detected antenatally. Ultrasound-guided needle biopsy if feasible could provide a reasonably confident diagnosis. Congenital anomalies in other organs should be looked for carefully.

Abdominal Neoplasms↗
PubMed2000

Health implications of musculoskeletal fitness.

Although it is well documented that physical activity participation can bring about improvements in musculoskeletal fitness, related health implications have only been substantiated in the elderly. Currently, interpretations of the results of musculoskeletal fitness appraisals for the general population are based largely on an intuitive belief that enhanced musculoskeletal fitness is associated with higher levels of health throughout adulthood. Musculoskeletal fitness was measured in 312 females and 259 males aged 15-69 years. Health levels were determined using two previously validated questionnaires and expressed as composite health scores derived from principal components analysis. Grip strength, push strength, pull strength, push-ups, and trunk forward flexion were significant predictors of health scores after controlling for the potentially confounding effects of gender age, aerobic fitness, waist circumference, and smoking status. These findings indicate that musculoskeletal fitness is related to health in males and females aged 15 to 69 years.

Adolescent↗
PubMed2000

The use of ascorbigen in the treatment of fibromyalgia patients: a preliminary trial.

Twelve female fibromyalgia syndrome (FMS) patients were given 500 mg per day of a blend containing 100 mg ascorbigen and 400 mg broccoli powder in a preliminary, one-month, open-label trial. This group of patients showed a mean 20.1 percent (p=0.044) decrease in their physical impairment score and a mean 17.8 percent (p=0.016) decrease in their total fibromyalgia impact scores as measured by the Fibromyalgia Impact Questionnaire. The mean physical impairment score two weeks post-treatment showed a significant return to near pre-treatment level (p=0.028). Analysis of ten of the patients' mean threshold pain levels at the 18 possible tender points obtained before and at the end of treatment showed a strong trend toward an increase in the mean threshold pain level (p=0.059). The reduced sensitivity to pain and improvement in quality of life measured in this study appear to be clinically relevant and a larger, double-blind study is warranted.

Ascorbic Acid↗
PubMed2000

Evaluation of a second set of lateral lasers for easier patient positioning in radiotherapy.

On modern linear accelerators patient set-up is often awkward due to the height of the isocentre. A second set of lateral lasers was mounted approximately 20 cm below the isocentre allowing patient positioning at an ergonomical height. A small randomised study involving 16 heavy patients treated for pelvic malignancies demonstrated that using the lower lasers for patient set-up is not only likely to reduce strain on staff but also speed up the set-up process.

Aged↗
PubMed1999

Police officers' detection of breath odors from alcohol ingestion.

Police officers frequently use the presence or absence of an alcohol breath odor for decisions on proceeding further into sobriety testing. Epidemiological studies report many false negative errors. The current study employed 20 experienced officers as observers to detect an alcohol odor from 14 subjects who were at blood alcohol concentrations (BACs) ranging from zero to 0.130 g/dl. Over a 4 h period, each officer had 24 opportunities to place his nose at the terminal end of a 6 in. tube through which subjects blew. Subjects were hidden behind screens with a slit for the tube to prevent any but odor cues. Under these optimum conditions, odor was detected only two-thirds of the time for BACs below 0.08 and 85% of the time for BACs at or above 0.08%. After food consumption, correct detections declined further. Officers were unable to recognize whether the alcohol beverage was beer, wine, bourbon or vodka. Odor strength estimates were unrelated to BAC levels. Estimates of BAC level failed to rise above random guesses. These results demonstrate that even under optimum laboratory conditions, breath odor detection is unreliable, which may account for the low detection rate found in roadside realistic conditions.

Adult↗
PubMed1999

Abuse of guaifenesin-containing medications generates an excess of a carboxylate salt of beta-(2-methoxyphenoxy)-lactic acid, a guaifenesin metabolite, and results in urolithiasis.

OBJECTIVES: Several urinary calculi were submitted to our institution for compositional analysis. The typical techniques of analysis, polarized light microscopy, electron microprobe analysis, and infrared spectroscopy proved inadequate for a definitive identification. As a result, a more detailed organic analysis was conducted to determine the exact chemical structure of the material. METHODS: Infrared spectroscopy and mass spectrometric analysis were carried out on the solid material, providing information concerning the functional groups and the molecular mass of the organic constituent and its components. The stone was solubilized in deuterated solvents and analyzed by nuclear magnetic resonance spectroscopy, which resulted in a definitive chemical structure. RESULTS: The spectroscopic analysis indicated that the stones were composed of a calcium salt of beta-(2-methoxyphenoxy)-lactic acid, a metabolite of the pharmaceutical guaifenesin, which is used as an expectorant. CONCLUSIONS: Guaifenesin, an expectorant common in over-the-counter cold and allergy remedies, can cause urolithiasis if taken in excess. Discussions with physicians and their patients confirmed that most patients admitted to taking large doses of guaifenesin-containing medications.

Adolescent↗
PubMed1999

Urban air particulate inhalation alters pulmonary function and induces pulmonary inflammation in a rodent model of chronic bronchitis.

Epidemiological studies have reported increased morbidity in human populations following inhalation of elevated levels of urban particulate matter. These responses are especially prevalent in populations with chronic obstructive pulmonary diseases, including chronic bronchitis. Toxicological studies have reported altered pulmonary function and increased pulmonary inflammation following particulate inhalation in the laboratory setting. However, most of these studies have utilized artificial particles that may not accurately mimic outdoor air pollutant conditions. Few studies have utilized actual urban air particle samples in inhalation studies. In the present study, the effects of inhaled concentrated urban air particulates on pulmonary function and pulmonary inflammation are addressed. Normal rats and rats with chronic bronchitis induced by approximately 200 ppm SO(2) for 6 wk were subsequently subjected to filtered air or concentrated air particles (CAPs). Twelve rats per group in 4 groups (48 rats total) were exposed for 5 h/day for 3 consecutive days. The CAPs aerosol levels were 206, 733, and 607 microg/m(3) (MMAD = 0.18 microm, sigma(g) = 2.9) on days 1, 2, and 3, respectively. Following the final day of exposure, pulmonary function parameters, including peak expiratory flow (PEF), tidal volume (TV), respiratory frequency (RF), and minute volume (MV), were measured and compared to preexposure baseline levels. Twenty-four hours following the final day of exposure, bronchoalveolar lavage was performed for total cell counts, differential cell counts, and total lavage protein levels. Pulmonary responses to CAPs in chronic bronchitic animals indicated a significant increase in tidal volume as well as peak expiratory flow. In CAPs-exposed animals without underlying bronchitis, significantly increased tidal volume was observed. Significant pulmonary inflammation was observed in the CAPs-exposed animals, particularly those with chronic bronchitis. Significant increases in neutrophils, lymphocytes, and total lavage protein were observed. These results suggest two distinct mechanistic responses to inhaled particles: a stress-type pulmonary function response marked by increases in flow and volume, that is, deeper breathing; and acute pulmonary inflammation marked by cellular influx, particularly neutrophils. From these data it is concluded that inhaled urban air particles alter pulmonary breathing parameters and increase pulmonary inflammation.

Air Pollutants↗
PubMed1999

Exercise cardiac function in young through elderly endurance trained women.

PURPOSE: To clarify the physiological reasons for the decline in aerobic power of endurance trained (ET) women with aging. METHODS: Blood volume, VO2max, and exercise cardiac function were examined in 23 ET women; six age 20-29 yr, six age 40-45 yr, six age 49-54 yr, and five age 58-63 yr. RESULTS: Blood volume was unchanged with aging. VO2max declined progressively at a rate of 0.51 mL x kg(-1) x min(-1) x yr(-1). During maximal exercise, there was an increase in total peripheral resistance (TPR) and a decrease in heart rate, stroke volume, and cardiac output with increasing age. At all ages, cardiac filling (diastole) was significantly faster than cardiac emptying (systole). Stroke volume did not plateau at a submaximal work rate but increased progressively to maximum. CONCLUSIONS: The decline in VO2max with age in ET women is due to decreases in maximal heart rate, stroke volume and cardiac output, and the primary advantage in the exercise cardiac performance of ET women of all ages is diastolic rather than systolic function.

Adult↗
PubMed1999

NS-398 upregulates constitutive cyclooxygenase-2 expression in the M-1 cortical collecting duct cell line.

The cortical collecting duct (CCD) is a major site of intrarenal prostaglandin E2 (PGE2) synthesis. This study examines the expression and regulation of the prostaglandin synthesizing enzymes cyclooxygenase-1 (COX-1) and -2 in the CCD. By indirect immunofluorescence using isoform-specific antibodies, COX-1 and -2 immunoreactivity was localized to all cell types of the murine M-1 CCD cell line. By immunohistochemistry, both COX-1 and COX-2 were localized to intercalated cells of the CCD on paraffin-embedded mouse kidney sections. When COX enzyme activity was measured in the M-1 cells, both indomethacin (COX-1 and -2 inhibitor) and the specific COX-2 inhibitor NS-398 effectively blocked PGE2 synthesis. These results demonstrate that COX-2 is the major contributor to the pool of PGE2 synthesized by the CCD. By Western blot analysis, COX-2 expression was significantly upregulated by incubation with either indomethacin or NS-398. These drugs did not affect COX-1 protein expression. Evaluation of COX-2 mRNA expression by Northern blot analysis after NS-398 treatment demonstrated that the COX-2 protein upregulation occurred independently of any change in COX-2 mRNA expression. These studies have for the first time localized COX-2 to the CCD and provided evidence that the intercalated cells of the CCD express both COX-1 and COX-2. The results also demonstrate that constitutively expressed COX-2 is the major COX isoform contributing to PGE2 synthesis by the M-1 CCD cell line. Inhibition of COX-2 activity in the M-1 cell line results in an upregulation of COX-2 protein expression.

Animals↗
PubMed1998

Do inflammatory processes contribute to radiation induced erythema observed in the skin of humans?

BACKGROUND: Two prospective trials were designed to determine whether there may be a role for inflammatory mediators in human skin erythema at both high and low doses per fraction and for 'out of field' effects. METHODS: Trial 1. Effects of topical indomethacin (1%) and hydrocortisone (1%) applied before and during radiotherapy were compared for erythema induced by 20 Gy in four fractions (n = 26, 6 MV). Trial 2. Effects of topical hydrocortisone (1 %) applied before and during radiotherapy and no medication were compared for erythema induced by 1, 3, 5 and 7 Gy in five fractions (n = 21, 120 kV). Erythema was measured using reflectance spectrophotometry (RFS) and laser Doppler (LD) on a weekly basis. RESULTS: Trial 1. A bi-phasic reaction time course was suggested in two-thirds of the cases. The first phase did not appear to be influenced by hydrocortisone cream but the second was significantly attenuated. Indomethacin had no effect on either reaction phase. Erythema measured several centimetres outside of the field was reduced by hydrocortisone but not by indomethacin. Trial 2. Trial 2 confirmed the presence of measurable erythema, invisible to the eye, that coincided in its time course to the first phase of erythema noted in trial 1. This reaction was more intense than predicted by the LQ formula and was non-significantly attenuated by topical hydrocortisone. RFS readings proved to be less subject to inter- and intra-patient variations than the LD unit used. CONCLUSION: Inflammatory responses may play a role in the mediation of the erythematous response to radiation in human skin. Further studies are warranted.

Aged↗
PubMed1998

Exercise cardiac function in endurance-trained males versus females.

OBJECTIVE: To examine and compare the exercise cardiac function of endurance-trained (ET) women and men. PARTICIPANTS: Six ET women aged 20 to 29 years (mean VO2max = 64 ml.kg-1.min-1) and 9 ET men aged 20 to 29 years (mean VO2max = 69 ml.kg-1.min-1) were included in the study. MAIN OUTCOME MEASURES: Cardiac output (Q), stroke volume (SV), diastolic filling rate (DFR), and left ventricular ejection rate (LVER) were compared at rest and during exercise at heart rates (HRs) of 110, 130, 150, 170 bpm, and max. Resting blood volume (BV) and hemoglobin concentration ([Hb]) were also compared. RESULTS: Compared to women, men had a higher BV and [Hb]. At HRmax, men had a higher Q (31.0 +/- 0.6 versus 24.1 +/- 0.9 l.min-1), SV, DFR, and LVER than women. When expressed relative to body mass (kg), there were no gender differences in SVmax, and women had a significantly higher a-v DO2max (approximately 19%) than men. The SV of the men and women did not plateau at a submaximal level but continued to increase progressively to HRmax. During maximal exercise, the DFR was significantly faster than the LVER in the men and the women. CONCLUSIONS: When ET men and women are matched for body mass, the gender difference in SVmax is reduced so that it is no longer statistically significant. However, there are still significant gender differences in Q, DFR, LVER, BV, and [Hb] that contribute to a higher VO2max (ml.kg-1.min-1) in ET men compared to women. To augment SVmax, women and men rely to a greater extent on diastolic filling than on left ventricular emptying.

Adult↗