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Biomedical subjects

R Bascom

Publications and source records attributed to R Bascom.

At least 19 recordsLinked to original sources
PubMed2000

The relationship between particle deposition in the anterior nasal passage and nasal passage characteristics.

The objective of this study was to examine the effects of nasal passage characteristics on anterior particle deposition during cyclical breathing. Forty healthy, nonsmoking, adult subjects participated in this study. Nasal passage characteristics such as nostril length, width, angle, ellipticity, and minimum nasal cross-sectional area were measured. The subjects inhaled a polydisperse radioactively tagged aerosol (mass median aerodynamic diameter = 5.4 microns, geometric standard deviation [GSD] = 1.3) into the nose and exhaled through the mouth. The amount of radioactivity in the nose was measured immediately after inhalation and thereafter for 54 minutes. At 52.5 minutes, subjects wiped the accessible portion of the anterior nose to remove any remaining activity. The difference in activity at 52 and 54 minutes was used as a measure of activity removed during the nose wipe. Percentage of activity in the nasal passage at 52 minutes and percentage of activity removed with the nose wipe were considered surrogates for particles deposited in the anterior nasal passage. A multiple regression analysis showed that the degree of ellipticity of the nostrils was significantly related to particle deposition in the anterior nasal passage. These results suggest that ellipticity of the nostrils may be a determinant of the amount of particle deposition in the anterior nasal passage.

Adult↗
PubMed1999

Bacterial endotoxin is an active component of cigarette smoke.

BACKGROUND: Chronic bronchitis in cigarette smokers shares many clinical and histologic features with environmental lung diseases attributed to bacterial endotoxin (lipopolysaccharide [LPS]) inhalation. Experimental LPS inhalation mimics many of the acute effects of cigarette smoke in the lower airway. Therefore, we reasoned that LPS may be a biologically active component of cigarette smoke. DESIGN: The Limulus amebocyte lysate (LAL) assay was used to measure LPS in the tobacco and filter tip components of unsmoked 1R4F experimental cigarettes and commercially available "light" cigarettes, as well as in mainstream (MS) and sidestream (SS) smoke particles generated with an automated smoking machine and collected on ventilator mainflow filters. SETTING AND PARTICIPANTS: Blood LPS activity and plasma cytokine concentrations were measured in groups of healthy smokers and nonsmokers who reported to the walk-in clinic at the Baltimore VA Medical Center for unrelated complaints. MEASUREMENTS: Blood LPS levels were measured by LAL assay and plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), soluble TNF receptors I and II (sTNFR I and sTNFR II) were measured by enzyme-linked immunosorbent assay. RESULTS: Bioactive LPS was detected in both the tobacco portion (1R4F, 17.8+/-1.0 microg/cigarette; light, 26.8+/-7.3 microg/cigarette [mean+/-SE]) and filter tips (1R4F, 0.67+/-0.55 microg/cigarette; light, 0.70+/-0.39 microg/cigarette) of cigarettes. Bioactive LPS was also detected in both MS (1R4F, 120+/-64 ng/cigarette; light: 45.3+/-16 ng/cigarette) and SS smoke (1R4F, 18+/-1.5 ng/cigarette; light: 75+/-49 ng/cigarette). Although systemic absorption of inhaled LPS may occur, we failed to detect any differences between nonsmokers and smokers in median blood LPS levels (median values, 66.75 and 72.1 pg/mL, respectively; p = 0.55) or plasma concentrations of TNF-alpha (0 vs 0 pg/mL, respectively; p = 0.71), sTNFR I(1,469 vs 1,576 pg/mL, respectively), sTNFR II (2,011 vs 3,110 pg/mL, respectively), or IL-6 (8.8 vs 0 pg/mL, respectively; p = 0.20). CONCLUSIONS: Smoking one pack of cigarettes per day delivers a dose of respirable LPS that is comparable to the levels of LPS associated with adverse health effects in cotton textile workers. Thus, we suggest that the bioactive LPS in cigarette smoke may contribute to the pathogenesis of chronic bronchitis that develops in susceptible cigarette smokers.

Bronchitis↗
PubMed1998

Acute respiratory response to prolonged, moderate levels of sidestream tobacco smoke.

Environmental tobacco smoke (ETS) is a significant component of indoor air pollution yet the acute upper respiratory response has not been well studied. The goal of this study was to determine the response of healthy subjects to moderate levels of sidestream tobacco smoke (SS). Twenty-three subjects were challenged on 2 separate days to clean air or SS (2 h, 15 ppm carbon monoxide, at rest). Subjects completed symptom questionnaires, posterior rhinomanometry, and body plethysmography. Average total and differential cell counts and albumin concentration were determined on nasal lavage samples. The urinary cotinine: creatinine ratio was used as a biomarker of exposure. Following SS exposure, irritant and rhinitis symptoms increased, nasal resistance rose from 4.9+/-0.4 to 6.3+/-0.6 cm H2O/L/s and specific airway conductance decreased from 0.14+/-0.01 to 0.13+/-0.01 cm H2O(-1) s(-1). Total cell counts, neutrophils, and albumin were unchanged. An increased nasal congestive response did not correlate with an increased cotinine: creatinine ratio. A history of ETS rhinitis did not predict an increased group response to smoke, but individuals with the largest physiologic and inflammatory response were historically ETS sensitive. In summary, healthy normal subjects demonstrate nasal congestion with exposure to moderate levels of SS without evidence of increased nasal vascular permeability.

Adolescent↗
PubMed1997

Glucocorticoids induce beta2-adrenergic receptor function in human nasal mucosa.

Glucocorticoids are hypothesized to induce beta2-adrenergic receptors (beta2-R) and their functions. The ability of dexamethasone (DEX) in vitro and beclomethasone dipropionate (BDP) in vivo to induce beta2-R messenger RNA (mRNA) and function was investigated in human nasal mucosa. In this tissue, albuterol does not stimulate exocytosis either in vivo or in vitro (Mullol and coworkers, 1992). Therefore, induction of beta2-R-mediated glandular exocytosis by glucocorticoids was proposed as an unambiguous outcome measure. Human nasal mucosa was cultured for 3 d with and without 1 microM DEX, then challenged with media or 100 microM albuterol. Culture supernatants were collected for measurement of exocytosed glandular products. Explant mRNA was extracted for reverse transcriptase-polymerase chain reaction (RT-PCR), and in situ hybridization of beta2-R mRNA performed. In vivo, normal subjects received saline or BDP for 3 d before albuterol nasal provocation. Concentrations of exocytosed products were measured in nasal secretions. RNA was extracted from nasal epithelial scrapings for RT-PCR. In vitro, DEX treatment induced albuterol-mediated glandular exocytosis (p < 0.04), and increased the steady-state beta2-R/beta-actin mRNA ratio (p < 0.05), and expression of beta2-R mRNA in glands. In vivo, BDP increased the beta2-R/beta-actin mRNA ratio in epithelial scrapings (p < 0.04), but did not induce albuterol-mediated glandular secretion. We conclude that glucocorticoids increase steady-state beta2-R mRNA levels in vivo and in vitro, and can induce beta2-R function as assessed by submucosal gland exocytosis in vitro. While topical BDP induced epithelial beta2-R mRNA, it did not modulate exocytosis from the deeper submucosal glands.

Administration, Topical↗
PubMed1997

Neurogenic inflammation: with additional discussion of central and perceptual integration of nonneurogenic inflammation.

The Working Group on Neurogenic Inflammation proposed 11 testable hypotheses in the three domains of neurogenic inflammation, perceptual and central integration, and nonneurogenic inflammation. The working group selected the term people reporting chemical sensitivity (PRCS) to identify the primary subject group. In the domain of neurogenic inflammation, testable hypotheses included: PRCS have an increased density of c-fiber neurons in symptomatic tissues; PRCS produce greater quantities of neuropeptides and prostanoids than nonsensitive subjects in response to exposure to low-level capsaicin or irritant chemicals; PRCS have an increased and prolonged response to exogenously administered c-fiber activators such as capsaicin; PRCS demonstrate augmentation of central autonomic reflexes following exposure to agents that produce c-fiber stimulation; PRCS have decreased quantities of neutral endopeptidase in their mucosa; exogenous neuropeptide challenge reproduces symptoms of PRCS. In the domain of perceptual and central integration, testable hypotheses included: PRCS have alterations in adaptation, habituation, cortical representation, perception, cognition, and hedonics compared to controls; the qualitative and quantitative interactions between trigeminal and olfactory systems are altered in PRCS; higher integration of sensory inputs is altered in PRCS. In the domain of nonneurogenic inflammation, testable hypotheses included: increased inflammation is present in PRCS in symptomatic tissues and is associated with a heightened neurosensory response; PRCS show an augmented inflammatory response to chemical exposure. The working group recommended that studies be initiated in these areas.

Chemoreceptor Cells↗
PubMed1996

Evaluation of acoustic rhinometry and posterior rhinomanometry as tools for inhalation challenge studies.

Objective measures of upper respiratory function are needed to understand the effects of inhaled toxicants on the nasal passages. Acoustic rhinometry (AR) is a simple new technique that determines nasal volume by measuring the cross-sectional area of the upper airway as a function of the distance along the nasal passage. This study compares acoustic rhinometry with the more traditional posterior rhinomanometry (NAR) and correlates these objective measures with the symptom of nasal congestion. Healthy young adults (n = 29) were studied on 4 days, each separated by at least 1 wk, in a climate-controlled environmental chamber for 6 h, with exposure to clean air or sidestream tobacco smoke (SS) (2 h, 1, 5, and 15 ppm CO). The coefficient of variation for single measurements was 8-15% (AR) and 4% (NAR); for across-day measurements it was 15-25% (AR) and 13-15% (NAR); and for between days it was 19-27% AR and 17-21% (NAR). These coefficients were similar in subjects with a history of environmental tobacco smoke sensitivity (ETS-S) and those with no history of ETS sensitivity (ETS-NS). At baseline, the perception of unilateral nasal congestion was significantly correlated with unilateral nasal dimensions or nasal resistance; the symptom of baseline bilateral nasal congestion (estimated for both nasal passages simultaneously) correlated less well with objective measures of nasal patency. Under challenge conditions (SS at 1-15 ppm CO), there were typically significant correlations between changes in unilateral congestion and both unilateral rhinomanometry and acoustic rhinometry, but correlations of bilateral congestion and measurable dimensions were much lower. ETS-S and ETS-NS subjects differed in correlations between bilateral subjective and objective measures: ETS-S subjects showed significant correlation between baseline congestion and NAR; in contrast, ETS-NS subjects showed significant correlation between baseline congestion and acoustic rhinometry. These results indicate that NAR and AR are complementary tests for use in inhalation challenge studies and have different correlations with nasal congestion under baseline and challenge conditions.

Acoustics↗
PubMed1996

Tobacco smoke upper respiratory response relationships in healthy nonsmokers.

This study determined exposure-response relationships to side-stream tobacco smoke (2 hrs; 0, 1, 5, and 15 ppm CO) in 29 healthy nonsmoking young adults. Sixteen subjects had no history of environmental tobacco smoke rhinitis (ETS-NS) while 13 subjects had a history of ETS rhinitis (ETS-S). Eye irritation and odor perception showed a statistically significant exposure response in both groups; headache was significant in ETS-S and nose irritation was significant in ETS-NS subjects. Significant postexposure (P1) symptoms were first reported at 1 ppm CO among both groups, but in 3/9 symptoms were significantly greater at this exposure level in ETS-S subjects. Nasal congestion, rhinorrhea, and cough increased significantly at 15 ppm CO only. In ETS-S subjects, nasal volume decreased and nasal resistance increased in an exposure-response fashion. ETS-NS subjects had a qualitatively different shape to the exposure-response curve; significant dimensional reductions in mid- and posterior nasal volume occurred with exposure at 1 ppm CO but not at 5 ppm CO and reductions in posterior nasal volume occurred at 15 ppm CO exposure. These studies indicate subjective and objective response relationships with exposure to sidestream tobacco smoke at concentrations from 1 to 15 ppm CO. Some differences are noted among the two subject groups in the magnitude of some symptoms at the lowest exposure level and in the qualitative shape of the acoustic rhinometry and nasal resistance exposure-response curves.

Adult↗
PubMed1996

Environmental factors and respiratory hypersensitivity: the Americas.

Diverse environmental exposure profiles exist in the Americas because of widely different climates, ambient pollutants, and bioaerosols in these continents. This paper reviews selected studies from the Americas that support the broad hypothesis that environmental factors contribute to respiratory hypersensitivity. Processes influenced by environmental factors include primary immunologic sensitization, the development and exacerbation of specific immunologic diseases and the activation of nonspecific mechanisms with tissue inflammation, injury and remodeling. Endpoints resulting from these processes include respiratory symptoms, diseases such as asthma, with measures of disease severity including medication use and hospitalization rates, and death due to cardiorespiratory disease. Studies associate sensitization rates to specific allergens with environmental factors such as humidity and indices of allergen exposure. Regional variation occurs with exposure to outdoor source pollutants such as ozone, but varies by household to bioaerosols such as dust mite, cat or cockroach allergen. Indoor allergens are associated with asthma while outdoor allergens are associated with allergic rhinitis. In a national survey, the atopic sensitization rate in the USA increased with urban residence (defined as towns of population > 2500) and varied by region. Controlled human challenge studies show that ozone increases the response of allergic subjects to allergen. Increased ambient photochemical pollution concentrations, of which ozone is an important component, are associated with increased emergency room visits for asthma in cities such as Toronto, New York, Atlanta, and Mexico City. In Sao Paolo, Brazil, mortality due to childhood respiratory disease was influenced by the ambient levels of NO2. Epidemiologic studies including the recent meta-analysis of a large, longitudinal study population associate ambient concentrations of particulate matter < 10 microns and respiratory symptoms, disease severity and increased cardiorespiratory deaths. Toxicology studies show that individual variation in responsiveness is important in nonspecific inflammatory responses to irritant pollutants such as ozone and environmental tobacco smoke. These studies indicate that environmental factors influence primary allergen sensitization, secondary allergic responses, the activation of nonspecific inflammatory responses, and the severity of respiratory diseases, including asthma.

Adolescent↗
PubMed1995

Nasal pressure-volume relationships determined with acoustic rhinometry.

Partitioning of ventilation has been hypothesized to be related to nasal pressure-volume relationships, relationships that have been difficult to measure. Regional differences in nasal passage pressure-volume relationships are likely because the nasal valve and anterior turbinate are structurally different, but both are altered by agents that alter vascular tone. This study determined nasal volume-to-pressure ratio (NVPR) on six healthy nonsmoking subjects by measuring nasal volume by using acoustic rhinometry at pressures ranging between -14 and +14 cmH2O on 3 days: baseline, after intranasal decongestion (oxymetazoline), and congestion (histamine). NVPR was lower in the nasal valve (0.07 +/- 0.01 cm3/cmH2O) than in the anterior portion of the turbinates (0.29 +/- 0.05 cm3/cmH2O; P < 0.005). Oxymetazoline decongestion decreased NVPR in the nasal valve by 23% and NVPR in the anterior portion of the turbinates by 47%. Histamine did not alter NVPR at either site. Nasal resistance changes correlated with changes in nasal valve and anterior turbinate volume. In summary, regional differences in nasal pressure-volume relationships exist and changes occur with pharmacologically induced vascular decongestion.

Acoustic Stimulation↗
PubMed1995

Sidestream tobacco smoke exposure acutely alters human nasal mucociliary clearance.

Nasal mucociliary clearance (NMC) is a biomarker of nasal mucosal function. Tobacco smokers have been shown to have abnormal NMC, but the acute effect of environmental tobacco smoke (ETS) on nonsmokers is unknown. This study evaluated acute tobacco smoke-induced alterations in NMC in 12 healthy adults. Subjects were studied on 2 days, separated by at least 1 week. Subjects underwent a 60-min controlled exposure at rest to air or sidestream tobacco smoke (SS) (15 ppm CO) in a controlled environmental chamber. One hour after the exposure, 99mTc-sulfur colloid was aerosolized throughout the nasal passage and counts were measured with a scintillation detector. Six out of 12 subjects showed more rapid clearance after smoke exposure than after air exposure, and 3/12 had rapid clearance on both days. However, substantial decreases in clearance occurred in 3/12 subjects, all of whom had a history of ETS rhinitis. In two subjects, more than 90% of the tracer remained 1 hr after tracer administration (2 hr after smoke exposure). Understanding the basis for biologic variability in the acute effect of tobacco smoke on NMC may advance our understanding of pathogenesis of chronic effects of ETS.

Adult↗
PubMed1994

Refining the locus for Best vitelliform macular dystrophy and mutation analysis of the candidate gene ROM1.

Vitelliform macular dystrophy (Best disease) is an autosomal dominant macular dystrophy which shares important clinical features with age-related macular degeneration, the most common cause of legal blindness in the elderly. Unfortunately, our understanding and treatment for this common age-related disorder is limited. Discovery of the gene which causes Best disease has the potential to increase our understanding of the pathogenesis of all types of macular degeneration, including the common age-related form. Best disease has recently been mapped to chromosome 11q13. The photoreceptor-specific protein ROM1 has also been recently mapped to this location, and the ROM1 gene is a candidate gene for Best disease. Using highly polymorphic markers, we have narrowed the genetic region which contains the Best disease gene to the 10-cM region between markers D11S871 and PYGM. Marker D11S956 demonstrated no recombinants with Best disease in three large families and resulted in a lod score of 18.2. In addition, a polymorphism within the ROM1 gene also demonstrated no recombinants and resulted in a lod score of 10.0 in these same three families. We used a combination of SSCP analysis, denaturing gradient gel electrophoresis, and DNA sequencing to screen the entire coding region of the ROM1 gene in 11 different unrelated patients affected with Best disease. No nucleotide changes were found in the coding sequence of any affected patient, indicating that mutations within the coding sequence are unlikely to cause Best disease.

Base Sequence↗
PubMed1991

Photoreceptor peripherin is the normal product of the gene responsible for retinal degeneration in the rds mouse.

Retinal degeneration slow (rds) is a retinal disorder of an inbred strain of mice in which the outer segment of the photoreceptor cell fails to develop. A candidate gene has recently been described for the rds defect [Travis, G. H., Brennan, M. B., Danielson, P. E., Kozak, C. & Sutcliffe, J. G. (1989) Nature (London) 338, 70-73]. Neither the identity of the normal gene product nor its intracellular localization had been determined. We report here that the amino acid sequence of the bovine photoreceptor-cell protein peripherin, which was previously localized to the rim region of the photoreceptor disk membrane, is 92.5% identical to the sequence of the mouse protein encoded by the normal rds gene. The differences between the two sequences can be attributed to species variation. Monoclonal antibodies were used with Western blot analysis to localize the wild-type mouse peripherin/rds protein to isolated mouse rod outer segments and to show that it, like bovine peripherin, exists as two subunits linked by one or more disulfide bonds. The relative amounts of peripherin/rds protein and rhodopsin in retinal extracts of normal and rds mutant mice were also compared. Identification of peripherin as the protein encoded by the normal rds gene and its localization to membranes of rod outer segments will serve as a basis for studies directed toward defining the role of this protein in the morphogenesis and maintenance of the outer segment and toward understanding the mechanism by which the rds mutation causes retinal degeneration.

Amino Acid Sequence↗
PubMed1991

Upper respiratory tract environmental tobacco smoke sensitivity.

Some patients report rhinitis symptoms after exposure to environmental tobacco smoke (ETS), but objective assessments of this response have been lacking. Furthermore, the mechanism of this response is unknown. We assessed the frequency of ETS-related symptoms by administering a questionnaire to 77 healthy nonsmoking young adults who were participating in an unrelated study. Of the subjects 34% (26 of 77) reported one or more rhinitis symptoms (congestion, rhinorrhea, or sneezing) following ETS exposure. We then exposed 10 historically ETS-sensitive (ETS-S) and 11 historically ETS-nonsensitive (ETS-NS) subjects to 15 min of clean air followed by 15 min of sidestream tobacco smoke (CO concentration of 45 parts per million). At selected time points during these procedures we recorded symptoms, posterior nasal resistance, and spirometry and performed nasal lavages. ETS-S but not ETS-NS subjects reported significant (p less than 0.01) increases in nasal congestion, headache, chest discomfort or tightness, and cough following exposure to sidestream tobacco smoke. Rhinorrhea symptoms were greater and more prolonged in ETS-S subjects compared to ETS-NS subjects. Significant (p less than 0.01) increases in perception of odor and in eye, nose, and throat irritation occurred in both study groups, but ETS-S subjects reported significantly more nose and throat irritation. No significant changes in posterior nasal resistance occurred in the ETS-NS group but a significant increase occurred in the ETS-S subjects, with the resistance rising from 3.8 +/- 0.5 cm H2O/L/s (mean +/- SE) preexposure to a peak of 8.0 +/- 2.7 cm H2O/L/s 20 min after completion of the smoke exposure (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

The upper respiratory tract: mucous membrane irritation.

Despite the widespread recognition that mucosal irritation is a cardinal feature of "sick-building syndrome," few data exist on the cause, natural history, or pathophysiology of upper respiratory mucous membrane irritation. The baseline prevalence of nasal symptoms among building occupants is often 20%, but in some studies it is as high as 50 to 60%. New techniques of nasal challenge and analysis of cells and mediators in nasal lavage fluid have proved useful in the assessment of rhinitis caused by antigens, cold air, and viruses, and these techniques are now being applied to the study the response to irritants. Human inhalation challenge studies have recently demonstrated a spectrum of sensitivity to environmental tobacco smoke, but the basis for this difference requires additional investigation. Animal and in vitro studies indicate that the chemosensitive neurons and airway epithelium may be critical targets for irritants that participate in the induction of inflammation. New research methods are needed, particularly to evaluate complaints of nasal congestion, drying, and irritation. Techniques should be developed that may be useful for field studies, where the health effects of a complex mixture are being assessed in a specific indoor environment. There exists a group of individuals who report a variety of symptoms on exposure to low levels of common volatile organic mixtures such as perfume, cigarette smoke, and cleaning agents. Some of these individuals report having occupied "sick buildings" during the time their symptoms began. Research is needed to understand the basis of their complaints, their etiology, and treatment.

Acrolein↗
PubMed1991

Effect of intranasal capsaicin on symptoms and mediator release.

Differential nasal responsiveness to environmental tobacco smoke (ETS) has been documented in humans and we hypothesized that this reflects differential responsiveness to c-fiber stimulation. We compared the response to intranasal capsaicin in subjects with and without a history of ETS-rhinitis. We challenged 10 ETS-sensitive and 11 ETS-nonsensitive subjects intranasally with 25 mg of lactose powder followed by 25 pg to 25 ng of capsaicin in 25 mg of lactose. Subjects rated nasal symptoms and underwent nasal lavage. In each lavage, the concentrations of albumin (an index of vascular permeability), kinins and histamine (a marker of mast cell activation) were measured. Nasal lavage tosyl-L-arginine methyl ester (TAME)-esterase activity, which can be a reflection of mast cell activation, increased vascular permeability or glandular secretion, was also determined. Subjects with a history of ETS-rhinitis reported more rhinorrhea than subjects without a history of ETS-rhinitis (P less than .01). No significant increase occurred in nasal lavage histamine, albumin or kinins in either subject group. TAME-esterase activity (presumably a reflection of increased glandular secretion) increased greater than 1000 cpm in 12/21 subjects (designated "TAME-producers"), but this was unrelated to ETS-sensitivity. TAME producers showed a dose-dependent increase in TAME-esterase activity, whereas TAME nonproducers showed no change at any capsaicin dose. We conclude that capsaicin causes nasal symptoms and glandular stimulation without evidence of increased vascular permeability or mast cell activation. ETS-rhinorrhea symptoms in humans appear related to c-fiber stimulation. The absence of c-fiber-induced glandular secretion, although not related to ETS-sensitivity, was associated with decreased sneezing and increased symptoms of capsaicin-induced nasal burning.

Administration, Intranasal↗