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Biomedical subjects

N Powell

Publications and source records attributed to N Powell.

At least 19 recordsLinked to original sources
PubMed2001

The immunomodulatory drugs cyclosporin A, mycophenolate mofetil, and sirolimus (rapamycin) inhibit allergen-induced proliferation and IL-5 production by PBMCs from atopic asthmatic patients.

We have used an optimized, physiologically relevant in vitro assay system to show that in a concentration-dependent fashion the immunomodulatory drugs cyclosporin A, mycophenolate mofetil, and sirolimus (rapamycin), as well as the glucocorticoid dexamethasone, inhibit allergen-driven T-cell proliferation and IL-5 production in PBMCs from allergen-sensitized atopic asthmatic individuals at physiologic concentrations. This effect of cyclosporin A might at least partially account for its established clinical efficacy in sparing systemic glucocorticoid therapy while improving lung function in chronic, severe, glucocorticoid-dependent asthma. The data are also compatible with the hypothesis that the newer immunomodulatory drugs mycophenolate mofetil and sirolimus exert similar effects, perhaps with a more favorable benefit/risk ratio.

Asthma↗
PubMed2001

The topical glucocorticoids beclomethasone dipropionate and fluticasone propionate inhibit human T-cell allergen-induced production of IL-5, IL-3 and GM-CSF mRNA and protein.

BACKGROUND: T-cell production of eosinophil-active cytokines (IL-5, IL-3, GM-CSF) is thought to be fundamental to asthma pathogenesis. Inhaled aeroallergens may be one important stimulus for T-cell cytokine production in asthma. OBJECTIVE: To compare the potency and efficacy of the topical anti-asthma glucocorticoids beclomethasone dipropionate (BDP) and fluticasone propionate (FP) in inhibiting allergen-driven peripheral blood T-cell proliferation and production of IL-3, IL-5 and GM-CSF mRNA and protein. METHODS: Peripheral blood mononuclear cells from six atopic asthmatics sensitized to house dust mite (HDM) were cultured in the presence of HDM and serial dilutions of BDP or FP in vitro. Cellular proliferation (7 days) and culture supernatant cytokine concentrations (6 days) were measured by uptake of tritiated thymidine and ELISA, respectively. Cytokine mRNA expression (24 h) was measured in three subjects using a quantitative PCR technique. RESULTS: Both BDP and FP inhibited allergen-induced T-cell proliferation, expression of IL-3, IL-5 and GM-CSF mRNA, and secretion of the corresponding proteins in a concentration-dependent fashion. FP was considerably more potent, but not more efficacious, in exerting these actions. CONCLUSIONS: Both BDP and FP have the potential markedly to inhibit allergen-induced T-cell production of asthma-relevant cytokines. This activity is effected at the level of T-cell proliferation and cytokine gene transcription. These properties may be key features of the anti-asthma activity of these drugs. The greater potency of FP in vitro may be responsible for its greater clinical potency.

Administration, Topical↗
PubMed2000

Radiofrequency (pacing and thermic effects) in the treatment of sleep-disordered breathing.

Radiofrequency, whether it is used for pacing or for its thermal liberation properties, has been investigated as a treatment for sleep-disordered breathing. Diaphragmatic pacing has a long history. The problems associated with pacing, which are related to patient selection, equipment failure, disturbances at the electrode/nerve interface, neuromuscular function failure, muscle fatigue, and the physiological consequences of stimulation, will have to be resolved with XIIth nerve stimulation. Radiofrequency thermal ablation has been applied on the tongue of an animal model. In man, turbinates, soft palate tissue and the base of tongue have been treated. These feasibility studies have demonstrated that obstructive sleep apnea syndrome and upper airway resistance syndrome can be completely controlled using radiofrequency thermal ablation in some subjects. These results can be obtained without complications related to speech, taste or swallowing. The treatment can be administered as an outpatient procedure, but many applications are needed, and treatment may span 6 months. Too high a level of radiofrequency will cause pain or otherwise avoidable complications. The determination of which patients will benefit most from these procedures will require further multi-center, placebo-controlled studies.

Ambulatory Care↗
PubMed2000

Upper airway resistance syndrome and its treatment.

Although upper airway resistance syndrome (UARS) is being recognized by a growing number of specialists, its prevalence remains unknown. UARS is associated with nocturnal and daytime complaints and oro-naso-maxillo-mandibular signs. Spectrum analysis of the nocturnal sleep EEG from the central leads indicates significant differences in absolute power in the 12-14 Hz and the 7-9 Hz bands of UARS patients compared to controls. The 0.5-2.0 Hz band also appears to be involved when analyses performed on matched controls are compared to results obtained in subjects treated with nasal CPAP. Several treatment avenues--nasal CPAP, dental devices, surgical procedures, and radiofrequency thermal ablation--have been used for the treatment of UARS. The number of subjects treated have been too low and the protocols too limited to arrive at appropriate outcome recommendations, but many of the approaches have shown positive results, suggesting the possibility of several treatment avenues.

Electroencephalography↗
PubMed1999

MRI assessment of the pre-vertebral soft tissues in acute cervical spine trauma.

This pictorial review illustrates the MRI appearances of pre-vertebral haematoma in acute cervical spine trauma. The review is based on 31 patients who underwent MRI within 5 days of injury. MRI showed pre-vertebral haematoma in 24 cases; soft tissue thickening was detected on conventional radiographs in 14 cases. MRI is more sensitive than radiography for the detection of pre-vertebral haematoma.

Cervical Vertebrae↗
PubMed1997

Passive constriction of the upper airway during central apneas: fiberoptic and EMG investigations.

We studied five adult male patients with central sleep apnea syndrome (> 75% of the monitored events being central) during sleep using a fiberoptic scope and EMG monitoring of the superior and middle constrictors of the pharynx and the genioglossus and geniohyoid muscles. The fiberoptic investigation revealed a spontaneous decrease in the size of the airway during central apneas, without negative intrathoracic pressure or activation of the superior and middle pharyngeal constrictor muscles. We found a mean maximum decrease of 71 +/- 7% in the cross-sectional area of the airway and an absence of superior-middle pharyngeal constrictor EMG discharge. We did not observe any complete collapses of the airway.

Adult↗
PubMed1997

Elevated expression of messenger ribonucleic acid encoding IL-13 in the bronchial mucosa of atopic and nonatopic subjects with asthma.

Local secretion of cytokines by T cells within the bronchial mucosa, with consequent selective eosinophil influx, has been implicated in the pathogenesis of bronchial asthma. The cytokine IL-13 exhibits activities (selective eosinophil vascular adhesion by very late antigen-4/vascular cell adhesion molecule-1 interaction and promotion of IgE synthesis and "T112-type" T cell responses) that may be relevant to this process. We hypothesized that, compared with conditions in control subjects, elevated expression of messenger ribonucleic acid (mRNA) encoding IL-13 is a feature of the bronchial mucosa of both atopic (positive skin prick test result to at least one of a range of common aeroallergens) and nonatopic (negative skin prick test results and serum total IgE concentrations within the normal range) subjects with asthma. With use of a semiquantitative reverse transcriptase-polymerase chain reaction technique, we measured the quantities (relative to beta-actin) of IL-13 mRNA in bronchial mucosal biopsy specimens from atopic and nonatopic subjects with asthma and atopic and nonatopic control subjects. Biopsy specimens from the subjects with asthma, whether the subjects were atopic or nonatopic, had statistically equivalent quantities of IL-13 mRNA relative to beta-actin, and these quantities were significantly elevated compared with those in specimens from both the atopic and nonatopic control subjects (p < or = 0.02 in each case), in which the quantities of IL-13 mRNA relative to beta-actin were also statistically equivalent. The quantities of IL-13 mRNA reflected the numbers of EG2+ eosinophils per unit area of submucosa in the biopsy specimens as determined by immunohistochemistry, which were statistically equivalent in the atopic and nonatopic subjects with asthma and significantly elevated as compared with those in both the atopic and nonatopic control subjects without asthma (p < or = 0.007 in each case). Taking the subjects with asthma as a group, no correlations were observed between the quantities of IL-13 mRNA (relative to beta-actin) and several measures of disease severity. These data are consistent with the hypothesis that IL-13 plays a role in the pathogenesis of both atopic and nonatopic asthma, at least partly through promoting recruitment of eosinophils to the bronchial mucosa, although other factors may be more important in regulating the severity of the disease.

Adult↗
PubMed1996

Antigenicity, cross-reactivity and surface exposure of the Neisseria meningitidis 37 kDa protein (Fbp).

The 37 kDa iron-repressible protein, Fbp, was purified from two Neisseria meningitidis strains by metal-affinity chromatography and used to obtain mouse monospecific polyclonal immune sera. Dot-blot, immunoblotting and whole cell ELISA results demonstrate that the Fbp is present in all 16 N. meningitidis and four commensal Neisseria species tested, is highly antigenic in mouse when injected in pure form, and shows intra- and inter-species antigenic homogeneity, anti-Fbp antibodies being fully cross-reactive using the techniques mentioned. We also found that Fbp molecules (or parts of them) are surface exposed, in disagreement with the proposed exclusively periplasmic localization, although anti-Fbp antibodies seem unable to block iron uptake or to induce complement-mediated killing of the meningococci. Taken along with the high immunogenicity of the purified protein and the complete cross-reactivity of the antibodies elicited, this suggests that the protective effect of the purified Fbp must be further studied to evaluate its inclusion in future vaccine trials.

Animals↗
PubMed1996

A reversible uvulopalatal flap for snoring and sleep apnea syndrome.

Velopharyngeal incompetence (VPI) is a recognized complication of uvulopalatopharyngoplasty (UPPP) for obstructive sleep apnea. A new uvulopalatal flap (UPF) technique that modifies the UPPP and reduces this risk is presented. The technique achieves the same anatomic results as the UPPP but is reversible. To evaluate clinical outcomes of this new procedure, selected variables were compared in patients who underwent UPPP and UPF procedures. Eighty patients were examined (59/80 UPF, 21/80 UPPP) in a prospective and consecutive manner. Subjects underwent polysomnography and extensive airway evaluations. The characteristics of all patients, at baseline, were evaluated. The study variables included age, sex, body mass index (BMI), palatal length (PNS P) in millimeters, respiratory disturbance index (RDI), lowest oxygen saturation during sleep and a subjective snoring scale. Sixty-seven of the 80 patients underwent simultaneous hypopharyngeal surgery. Data were analyzed with a SAS program. No statistical difference existed between groups. The postoperative character of the palate and the change in snoring scores were the same in all patients (p = 0.584). A positive correlation existed between improvement in the snoring score and the amount of tissue removed or repositioned in the patients treated with UPF (correlation coefficient = 0.370, p = 0.004). In contrast, there was a negative correlation in the UPPP group for the same parameters (correlation coefficient = -0.195, P = 0.409). This suggests there was a difference between these two groups despite the fact that the baseline and postoperative lengths, as well as tissue removed or repositioned, were equivalent. This further suggests that the UPF may reduce snoring to a greater extent than the UPPP. No significant complications were seen in either group. There was no evidence of VPI, even in the early postoperative period. The new reported procedure is reversible and conservative and reduces the risk of VPI. Snoring is improved, which is consistent with a decrease in airway resistance or obstruction.

Adult↗
PubMed1996

Increased expression of mRNA encoding RANTES and MCP-3 in the bronchial mucosa in atopic asthma.

The selective recruitment of eosinophils into the mucosal lining of the airways is a prominent feature of atopic asthma, and is believed to be an important component in the disease pathogenesis. The precise stimuli responsible for the influx of eosinophils remain unclear. Using a semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) technique, the numbers of copies (relative to the "housekeeping" gene beta-actin) of messenger ribonucleic acid (mRNA) encoding the eosinophil-active chemotactic cytokines, the factor regulated upon activation in normal T-cells expressed and secreted (RANTES) and monocyte chemotactic protein-3 (MCP-3), was measured in bronchial biopsies from atopic asthmatic patients (n = 9), and compared with atopic nonasthmatic (n = 8) and nonatopic nonasthmatic (n = 8) control subjects. In addition, further biopsies from each subject were prepared for immunohistochemistry and the numbers of activated (EG2+) eosinophils measured. The expression of RANTES mRNA was significantly elevated in the atopic asthmatic group as compared to the atopic nonasthmatic controls (p = 0.013) and the nonatopic nonasthmatic controls (p = 0.007). Similarly, the expression of mRNA encoding MCP-3 was significantly elevated in the atopic asthmatic group, relative to the atopic nonasthmatic controls (p = 0.014) and the nonatopic nonasthmatic control group (p = 0.011). Elevated RANTES and MCP-3 mRNA expression was associated with significantly increased numbers of bronchial mucosal eosinophils in the atopic asthmatic patients as compared to the atopic nonasthmatic (p = 0.03) and nonatopic nonasthmatic (p = 0.006) control subjects. In conclusion, we have identified elevated expression of messenger ribonucleic acid encoding RANTES and monocyte chemotactic protein-3 in the bronchial mucosa of atopic asthmatic patients relative to controls. These findings are compatible with the hypothesis that eosinophil-active beta-chemokines play a role in the mechanism of eosinophil recruitment to the asthmatic bronchial mucosa.

Actins↗
PubMed1996

Evidence that guanylate cyclase is involved in modulating the resting tension and neurally-induced contraction of the guinea pig tracheal muscle.

Electrical field stimulation of guinea-pig tracheal muscle strips produced a frequency-dependent biphasic response consisting of an initial cholinergic contraction followed by relaxation. Both phases of the response were of neural origin. In the presence of methylene blue, a guanylate cyclase inhibitor, the resting tension and the contraction were increased, but the accompanying relaxation was inhibited. However, in the presence of sodium nitroprusside, a guanylate cyclase activator, the resting tension was reduced and the contraction was inhibited, but the relaxation was prolonged and increased. Similarly, in the presence of either 3-isobutyl-1-methylxanthine, which promotes cyclic guanosine monophosphate (cGMP) accumulation, or 8-bromo-cGMP, an analogue of cGMP, the resting tension was reduced and the contraction was inhibited but the relaxation was prolonged and increased. From these results, it is concluded that guanylate cyclase is involved in modulating the resting tension and the neurally-induced contraction of guinea-pig tracheal muscle.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Buoyant density of Escherichia coli is determined solely by the osmolarity of the culture medium.

In previous studies, we had shown that the buoyant density of Escherichia coli is determined by the osmolarity of the growth medium by varying the osmolarity of the medium with NaCl or sucrose. However, the buoyant density of the cells always exceeded that of the growth medium. Here we determined the effect of medium with a buoyant density greater than the expected buoyant density of cells by adding Nycodenz to Luria broth. Percoll gradients of cells were analyzed by laser light scattering. The buoyant density for 125- and 375-mOsM-grown cells was 0.002 g/ml and 0.003 g/ml more, respectively, for cells grown in the presence of Nycodenz than those grown without Nycodenz, while the buoyant density of 250-mOsM-grown cells was 0.005 g/ml less for cells grown in the presence of Nycodenz than those grown without Nycodenz. Cells grown in 500-mOsM medium with or without Nycodenz had the same buoyant density. The buoyant density of cultures grown in defined medium was the same as those grown in rich medium, with only the medium osmolarity correlating to buoyant density. We conclude from these experiments that neither buoyant density nor chemical make-up of the medium determines the buoyant density of cells grown in that medium. Only the medium osmolarity determines cell buoyant density, suggesting that E. coli has no mechanisms to sense buoyant density.

Centrifugation, Density Gradient↗
PubMed1995

The effect of electrical stimulation on obstructive sleep apnea syndrome.

Patients with severe obstructive sleep apnea polygraphically documented underwent electrical stimulation treatment trials. Submental and intraoral stimulations were applied during waking and during nocturnal sleep. The stimulation was applied using a custom-designed neuromuscular electrical stimulator (EdenTec Corp) providing symmetric biphasic constant voltage pulses. Pulse duration of each phase was set to 80 microseconds based on a subjective evaluation of pulse durations from 80 to 300 microseconds to minimize sensation while generating equivalent motor responses. Pulse repetition rate was set to 50 pulses per second. Cephalometric radiographs and endoscopies were obtained with and without stimulations during waking. Most commonly, stimulations induced alpha EEG arousals. Submental subcutaneous stimulation induced good contractions of platysmal muscles but had no impact on the upper airway. Intraoral stimulation induced clear tongue muscle movements but with change of shape of the upper airway and posterior movements of the tongue. Each time a breakage of apnea was noted, it was associated with a time-linked alpha EEG arousal. The results obtained by us and others do not, at this time, give convincing support for the use of electrical stimulation using submental surface or intraoral electrodes as a viable approach for effective control of obstructive sleep apnea syndrome symptoms.

Electric Stimulation Therapy↗
PubMed1995

Familial aggregates in obstructive sleep apnea syndrome.

Obstructive sleep apnea syndrome (OSAS) was diagnosed in157 subjects based on clinical symptoms, physical evaluation, cephalometric x-ray films, and polysomnography. These index cases identified 844 living first-degree relatives. Mailings were sent to 792 (94%). The mailing consisted of two identical questionnaires, one for the family member of the index case and one to be given to a friend (not a relative) of approximately the same age. In response, we received 531 (63%) questionnaires from relatives and 198 (25%) questionnaires from age-matched nonrelated friends, which were used as a control group. A more extensive investigation was performed on first-degree relatives of the index group living in the San Francisco Bay Area or vicinity. Two hundred seventy-nine relatives (100%) were identified. One hundred sixty-six subjects (59%) as well as 69 age-matched friends (ie, 41% of the 166 relatives and 25% of the potential total group) agreed to participate in further studies. These subjects had interviews, clinical investigations, and nonattended ambulatory monitoring. Cephalometric x-ray films could be obtained on only 22 of 166 participating relatives and 6 of 69 friends. Body mass index was not a differentiating measure between relatives and friends. Odds ratios (ORs) were calculated from the questionnaiare data. The report of tiredness, fatigue, and sleepiness did not distinguish family members from friends. The OR, however, progressively increases when there is a positive history of near nightly loud snoring (OR = 1.78; 95% confidence interval [CI] 1.25-2.54) or a positive history of daytime sleepiness in conjunction with near nightly loud snoring (OR = 3.11; 95% CI = 1.94-4.99). The investigation in the Bay Area indicated that, when first-degree relatives were compared with friends, the complaint of daytime tiredness, sleepiness, or both with the presence of a high and narrow(ogival) hard palate sharply differentiated between friends and relatives (OR = 10.9, 95, CI = 5.31-22.5). An Epworth Sleepiness Scale score of 9 or greater with the presence of another symptom associated with OSAS, and a respiratory disturbance index greater than 5 (number of apneas and hypopneas per hour of sleep > 5) gave an OR of 45.6 (95% CI = 18.8-11.0). Disproportionate craniofacial anatomy was common in familial groups with OSAS. Craniofacial familial features can be a strong indicator of risk for the development of OSAS.

Adolescent↗
PubMed1994

A framework for IS200, 16S rRNA gene and plasmid-profile analysis in Salmonella serogroup D1.

Chromosomal fingerprinting of the type strains of serotypes of Salmonella O-serogroup D1 with the DNA insertion sequence IS200 generated patterns which were either serotype-specific (e.g., Typhi), or conserved among groups of related serotypes (e.g., Dublin, Rostock and certain phage types of Enteritidis). The number of IS200 copies varied considerably, and the IS200 patterns of type strains of serotypes associated with systemic infections in man were specific and suitable for identifying strains within those serotypes. Polymorphism at 16S rRNA gene loci was examined among type strains and 11 16S rRNA gene profiles were characterised. The most prevalent of these was conserved among type strains of 11 serotypes, and the next most prevalent among type strains of nine serotypes; together, they encompassed 15 unique IS200 profiles. The distribution and mol. wts of plasmids carrying spvBC (virulence) genes could be directly related to certain chromosomal genotypes defined by IS200 patterns. The presence of virulence plasmids in serotypes Lomalinda, Antarctica and Wangata is reported for the first time. Comparison of 16S rRNA gene profiles and IS200 patterns provides a definition of genotype that is applicable to epidemiological studies of various group D1 serotypes and should prove particularly useful for those lacking plasmid DNA.

Blotting, Southern↗