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Biomedical subjects

D P Skoner

Publications and source records attributed to D P Skoner.

At least 19 recordsLinked to original sources
PubMed1997

Social ties and susceptibility to the common cold.

OBJECTIVE: To examine the hypothesis that diverse ties to friends, family, work, and community are associated with increased host resistance to infection. DESIGN: After reporting the extent of participation in 12 types of social ties (eg, spouse, parent, friend, workmate, member of social group), subjects were given nasal drops containing 1 of 2 rhinoviruses and monitored for the development of a common cold. SETTING: Quarantine. PARTICIPANTS: A total of 276 healthy volunteers, aged 18 to 55 years, neither seropositive for human immunodeficiency virus nor pregnant. OUTCOME MEASURES: Colds (illness in the presence of a verified infection), mucus production, mucociliary clearance function, and amount of viral replication. RESULTS: In response to both viruses, those with more types of social ties were less susceptible to common colds, produced less mucus, were more effective in ciliary clearance of their nasal passages, and shed less virus. These relationships were unaltered by statistical controls for prechallenge virus-specific antibody, virus type, age, sex, season, body mass index, education, and race. Susceptibility to colds decreased in a dose-response manner with increased diversity of the social network. There was an adjusted relative risk of 4.2 comparing persons with fewest (1 to 3) to those with most (6 or more) types of social ties. Although smoking, poor sleep quality, alcohol abstinence, low dietary intake of vitamin C, elevated catecholamine levels, and being introverted were all associated with greater susceptibility to colds, they could only partially account for the relation between social network diversity and incidence of colds. CONCLUSIONS: More diverse social networks were associated with greater resistance to upper respiratory illness.

Adolescent↗
PubMed1997

The relationship between airway hyperreactivity (AHR) and sodium, potassium adenosine triphosphatase (Na+,K+ ATPase) enzyme inhibition.

Previous studies have documented the presence of a sodium, potassium adenosine triphosphatase (Na+,K+ ATPase) enzyme inhibitor on platelet membranes and in the plasma of patients with allergy, many of whom historically had airway hyperreactivity (AHR). The purpose of this study was to investigate the relationship between methacholine AHR and Na+,K+ ATPase enzyme inhibition. In the first experiment, 47 adult subjects (13 allergic, 5 potentially allergic, 12 asthmatic, and 17 control subjects) were tested for platelet membrane Na+,K+ ATPase inhibition and AHR. Area under the methacholine dose-response curve (AUC) was expressed as percent baseline FEV1 x log concentration of methacholine (log [mg/ml]) and plotted as a function of the difference in postfreezing and prefreezing platelet membrane Na+,K+ ATPase activities (reflective of membrane-bound inhibitor), which was expressed as nanomoles per microgram of protein per minute (nmol/microg protein/min). A significant (r = -0.44, p < 0.005) negative correlation between the two was detected, such that high levels of AHR (low AUC) were associated with high levels of membrane-bound inhibitor. To test for a causal relationship between the two, the ability of a Na+,K+ ATPase inhibitor to directly influence the level of AHR was determined in a second experiment. Eight allergic and 10 control subjects were administered AHR tests on 2 different days, immediately after inhalation of either nebulized ouabain (1 mg) or placebo in a double-blind fashion. Ouabain versus placebo inhalation decreased the PC20 in four of the patients with allergy. Additionally, ouabain increased methacholine AHR in patients with allergy, as manifested by a lower AUC in seven of the eight patients. In contrast, the mean AUC for the ouabain versus placebo prechallenges did not change significantly in the control group. Finally, a positive correlation was demonstrated between the levels of platelet membrane Na+,K+ ATPase inhibition and bronchial responsiveness to ouabain (r = 0.49, p < 0.05). These results provide both correlative and mechanistic evidence for a causal relationship between Na+,K+ ATPase enzyme inhibition and AHR.

Adult↗
PubMed1997

Inhibition of the sodium, potassium adenosine triphosphatase enzyme in peripheral blood mononuclear cells of subjects with allergic rhinitis.

BACKGROUND: Previous investigations have documented that a sodium, potassium adenosine triphosphatase (Na+,K+ ATPase) enzyme inhibitor is bound to the platelet membrane, displaced from the platelet membrane by freezing, and present in the plasma of subjects with allergic rhinitis. Others have shown that stimulation of Na+,K+ ATPase is an important early event in mitogen-induced activation of peripheral blood mononuclear cells. OBJECTIVE: The purpose of this study was to determine whether the Na+,K+ ATPase enzyme inhibition observed in the platelets of subjects with allergic rhinitis also extends to peripheral blood mononuclear cells. METHODS: Na+,K+ ATPase activity of a particulate fraction of sonicated peripheral blood mononuclear cells was determined by spectrophotometry in asymptomatic adults with and without allergic rhinitis. RESULTS: The mean Na+,K+ ATPase activity of peripheral blood mononuclear cells expressed as nanomoles per microgram protein per minute (nM/ microgram protein/ min) +/-1 standard deviation of the subjects with allergic rhinitis (n = 14) was 1.04 +/- 1.01, while that of the control subjects (n = 12) was 3.57 +/- 1.60 (P < or = .001). In contrast, when the peripheral blood mononuclear cell membranes were frozen and then thawed prior to assay, the mean Na+,K+ ATPase activity for the subjects with allergic rhinitis (n = 24) was 5.33 +/- 2.62, while that of the control subjects (n = 23) was 1.12 +/- 1.24 (P < or = .001). Samples from a subset of subjects (n = 5) were assayed for both pre-freezing and post-freezing Na+,K+ ATPase activity. The freezing process was associated with a striking increase in Na+,K+ ATPase levels of subjects with allergic rhinitis (4.42 +/- 2.06) but a decrease in those of the control subjects (-3.89 +/- 0.95; P < or = .001). CONCLUSIONS: These data demonstrate that peripheral blood mononuclear cells from subjects with allergic rhinitis, like platelets, possess a membrane-bound Na+,K+ ATPase inhibitor that is displaced from the membrane by freezing. In vivo Na+,K+ ATPase inhibition could have significant effects on the activation and function of peripheral blood mononuclear cells in subjects with allergic rhinitis.

Freezing↗
PubMed1997

Inhibition of peripheral blood mononuclear cell proliferation by cardiac glycosides.

INTRODUCTION: Prior studies have shown that ouabain, a cardiac glycoside that inhibits the sodium, potassium adenosine triphosphatase (Na+,K+ ATPase) enzyme, downregulates phytohemagglutinin (PHA)-induced peripheral blood mononuclear cell (PBMNC) proliferation. OBJECTIVE: This study examined and compared the effects of both ouabain and digoxin, a cardiac glycoside used therapeutically in humans, on PBMNC proliferation. METHODS: Peripheral blood mononuclear cells were isolated from healthy human subjects, incubated for 72 hours with and without PHA (2%) in the presence and absence of ouabain (10(-12) M to 10(-4) M) or digoxin (10(-9) M to 10(-6) M), and pulsed with 3H thymidine. RESULTS: For PHA-stimulated PBMNCs in the ouabain-treated group (n = 10 subjects), the mean (+/-STD) % uptake (% 3H thymidine uptake in absence of ouabain) was 80.5 +/- 6.0 at 10(-12) M ouabain, 73.1 +/- 8.4 at 10(-10) M, 47.89 +/- 13.1 at 10(-8) M, 6.9 +/- 3.2 at 10(-6) M, and 3.4 +/- 1.6 at 10(-4) M. For PHA-stimulated cells in the digoxin-treated group (n = 9 subjects), the mean (+/-STD) % uptake (% 3H thymidine uptake in absence of digoxin) was 89.8 +/- 9.8 at 10(-9) M digoxin, 92.6 +/- 8.2 at 10(-8) M, 54.3 +/- 19.8 at 10(-7) M, and 1.0 +/- 2.4 at 10(-6) M. Repeated measures ANOVA demonstrated a significant effect of concentration of both glycosides on PBMNC proliferation (P < .01). The inhibitory effect was reversible, but was largely abbrogated if ouabain was added after 48 hours of incubation with PHA. Further, the inhibitory effect extended to PBMNCs stimulated with recall antigen (tetanus) and to fractionated PBMNCs (CD4+, CD8+ and CD19+) stimulated with mitogens. Additionally, dose-response inhibitory effects of glycosides on PBMNC Na+,K+ ATPase enzyme activity and interleukin-2 (IL-2) secretion by PHA-stimulated PBMNC were also noted. Neither glycoside had an effect on spontaneous PBMNC proliferation (no PHA) or trypan blue exclusion. CONCLUSIONS: These studies demonstrate that both cardiac glycosides inhibited PHA-induced PBMNC proliferation, possibly via Na+,K+ ATPase inhibition, but not via cell toxicity. The concentration range over which inhibition was observed was similar for both glycosides. The results raise the possibility that therapeutic or toxic doses of digoxin could have an effect on cell-mediated immunity in vivo.

Adult↗
PubMed1996

Suppression of in vivo cell-mediated immunity during experimental influenza A virus infection of adults.

A variety of recent evidence documents that otitis media is a frequent complication of upper respiratory tract viral infections. This relationship has been attributed to the interaction of a number of virus-provoked host responses, including eustachian tube dysfunction, changes in nasopharyngeal bacterial flora and suppressed immune function. The present study examined the effect of experimental influenza A virus infection on immune function as assessed by delayed skin test reactivity to candida, tetanus, and diphtheria/tetanus antigens in healthy adults with (n = 12) and without (n = 15) allergic rhinitis. All subjects became infected with the challenge virus as evidenced by viral shedding into nasal secretions and/or a four-fold rise in convalescent serum antibody titers compared to baseline. Intradermal skin tests were placed at baseline and 2, 4, 17, and 24 days after intranasal influenza A inoculation, the reactions were imaged and recorded 48 h after placement, and response areas were calculated by computerized digitization. The average combined areas for the three antigens (+/- S.T.D.) on each of the 5 study days were 1.4 +/- 1.4, 0.7 +/- 0.7, 0.6 +/- 0.6, 1.4 +/- 1.4, and 1.2 +/- 1.2 cm2, respectively. The responses to candida, but not tetanus and diphtheria/tetanus, returned to baseline levels by day 17. Repeated measures ANOVA documented significant effects of study day and antigen, but not allergy status. These results show that experimental influenza A infection suppressed delayed hypersensitivity skin tests in both allergic and non-allergic subjects, and suggest that alterations in immune function may contribute to otitis media.

Adolescent↗
PubMed1996

Effect of influenza A virus infection on natural and adaptive cellular immunity.

Influenza A virus (FLU) is an important pathogen in humans. Although many features of the antiviral immune response have been elucidated in murine and human models of disease, little is known about the role of NK cells, which provide natural, innate immunity. The effects of experimental intranasal FLU (H1N1) inoculation on NK cells and other immune parameters were studied in 18 healthy, adult volunteers during the acute and convalescent phases of infection. Peripheral blood mononuclear cells (PBMNC) were assayed at baseline and on Postinoculation Days 1, 3, 4, 6, 7, 23, and 44. FLU infection and pathophysiologic upper airway responses were documented in all subjects, and there was no mortality. During both the acute (Days 1-3) and the convalescent (Days 23 and 44) stages of the FLU infection, significant increases in NK activity and decreases in the number of activated NK cells were observed. Reductions in the absolute number of T lymphocytes and in PBMNC proliferation to FLU virus antigen and mitogen were also observed. The current investigation extended those findings to include reductions in the number of CD4+ and CD8+ T lymphocytes and increases in the number of activated T lymphocytes. These results document that FLU infection was accompanied by enhancement of natural immunity and, as expected, suppression of most of the other measured parameters of cellular immunity. The normal response to FLU infection in humans may involve sequential modulation of the different components of the cellular immune system.

Adult↗
PubMed1996

Modulation of histamine release by sodium, potassium adenosine triphosphatase inhibition.

BACKGROUND: Previous studies have shown that a sodium, potassium adenosine triphosphatase inhibitor is present in the plasma of allergic subjects in whom enhanced histamine releasability has also been reported. PURPOSE: The purpose of this study was to determine the effect of in vitro sodium, potassium adenosine triphosphatase inhibition on whole blood histamine release. METHODS: Samples obtained from 12 patients with allergic rhinitis and 12 nonallergic subjects were incubated in duplicate for 30 minutes with anti-IgE antibody (100 micrograms/mL) or control buffer following a 0-, 10-, 20-, 30-, 60-, 120- and 180-minute preincubation with ouabain (3.0 mM) or diluent. Cell supernatants were assayed for histamine by radioimmunoassay and results were expressed as a percentage of total histamine release. RESULTS: Mean (+/- 1 SEM) anti-IgE induced release, in the presence and absence of ouabain, respectively, for allergic subjects was 27.5 +/- 5.5 and 21.0 +/- 4.5 (ten minutes, P < 0.05), 30.3 +/- 6.0 and 22.4 +/- 4.8 (20 minutes, P < .025), 28.9 +/- 5.2 and 23.5 +/- 4.1 (30 minutes), 33.8 +/- 7.1 and 26.7 +/- 5.4 (60 minutes, P < .05), 43.2 +/- 7.5 and 24.3 +/- 4.6 (120 minutes, P < .001), and 34.5 +/- 5.0 and 29.8 +/- 5.4% (180 minutes). Spontaneous histamine release in allergic subjects was also significantly increased by ouabain. Mean (+/- SEM) spontaneous release, in the presence and absence of ouabain, respectively, for allergic subjects was 2.0 +/- 0.5 and 0.9 +/- 0.2 (60 minutes, P < .025), 2.8 +/- 0.5 and 1.9 +/- 0.4 (120 minutes, P < .05), and 5.4 +/- 1.5 and 3.9 +/- 0.8% (180 minutes, P < .005). Ouabain did not significantly alter histamine release in non-allergic subjects. CONCLUSIONS: These data show that ouabain induced a significant increase in both spontaneous and induced histamine release in allergic subjects. In vivo, sodium, potassium adenosine triphosphatase inhibition may have an effect on histamine release in allergic subjects.

Adult↗
PubMed1996

Extended-release albuterol in the treatment of 6- to 12-year-old asthmatic children.

BACKGROUND: Albuterol sulfate, in the syrup and tablet form for oral administration, has been an effective treatment for adults and children with bronchial asthma. Extended-release albuterol sulfate tablets (Proventil Repetabs, Schering Corp.) provide a convenient, twice-daily dosing regimen, but are indicated only for patients > or = 12 years of age. OBJECTIVE: This study was undertaken to determine whether patients 6 to 12 years of age could be effectively and safely treated with extended-release albuterol tablets. METHODS: This was a randomized, double-blind, placebo-controlled, parallel group study of 157 patients in five centers. Patients were randomized to 4 weeks' treatment with extended-release albuterol tablets, 4 mg twice daily (q 12h), increasing up to 12 mg q 12h, or placebo. Efficacy was evaluated based on pulmonary function tests (PFTs), physician and patient evaluations, and data collected from patients' diaries on PEFR, asthma symptoms, number of nighttime awakenings, and number of tablets taken. The primary efficacy parameter was area under the curve (AUC) for FEV1, evaluated for 8 to 12 hours post-dosing. Safety was evaluated based on vital signs, electrocardiograms, and adverse events. RESULTS: Mean AUCs for FEV1 were significantly greater in the albuterol group at days 1 and 8 (P < or = .03). The albuterol group showed consistently lower severity scores for asthma symptoms. Physicians' and patients' global evaluations favored the albuterol group over the placebo group. No serious, treatment-related adverse events were reported. There were no clinically meaningful changes from baseline in either treatment group for vital signs or electrocardiograms. CONCLUSIONS: Extended-release albuterol tablets (4 mg), administered to children 6 to 12 years old in divided doses of up to 24 mg/day, improved pulmonary function and asthmatic symptoms and were well tolerated.

Adolescent↗
PubMed1996

Prechallenge antibodies: moderators of infection rate, signs, and symptoms in adults experimentally challenged with rhinovirus type 39.

This study determined the influence of serum neutralizing antibody titers on infection rate, symptom manifestations, and provoked signs and pathophysiologies in adults experimentally exposed to rhinovirus type 39 (RV-39). Antibody status was determined for 151 healthy volunteers who were then cloistered in a hotel for 6 days. At the end of the first cloister day, the volunteers were challenged with RV-39 in a median tissue culture infective dose of 100. On each of the 6 days, a nasal examination was performed, symptoms were scored, and objective tests of nasal mucociliary function, nasal airway patency, secretion production, and middle ear pressures were completed. Both subjects and investigators were blinded to the prechallenge serum homotypic antibody titers of the subjects. Four subjects presented with a wild virus and were excluded from the analysis. Of the 147 included subjects, prechallenge serum antibody titers to RV-39 were low (under 2) in 56 subjects, intermediate (2 to 8) in 51 subjects, and high (above 16) in 40 subjects. The high-titer group was significantly different from the low-titer group with respect to viral shedding, symptom load, subjective extent of illness, and secretion production, as well as in the frequency of subjects with abnormal nasal mucociliary clearance and positive middle ear pressures. The study results document that for experimental RV-39 exposure, high levels of homotypic serum neutralizing antibody titers are associated with protection from infection and a lessened degree of disease expression, but not with a reduction of otologic complications.

Adolescent↗
PubMed1996

Lower airway responses to influenza A virus in healthy allergic and nonallergic subjects.

Acute asthma is considered a complication of respiratory viral infections. This investigation assessed the effects of influenza A virus infection on both the patency and responsiveness of the lower airways. Subjects with allergic rhinitis (AR; n = 21) and without AR (non-AR; n = 25) were intranasally inoculated with influenza A virus and monitored for 8 d in a cloistered environment for changes in symptoms, signs, and airway physiology (pulmonary function, bronchial methacholine provocation). All subjects were infected after inoculation. Significant increases in nasal symptoms and secretion weights were observed, with peak effects on Days 3 and 4. Cough was a relatively minor symptom, and none of the subjects developed wheezing. Likewise, there were no significant changes in the measured functions of the lower airways. No effects on allergy status were observed. Under these experimental conditions, influenza A virus infection did not produce detectable alterations in lower airway function in health AR and non-AR subjects.

Adult↗
PubMed1996

Lower airway responses to rhinovirus 39 in healthy allergic and nonallergic subjects.

Acute asthma is considered to be a complication of respiratory viral infections. This investigation assessed the effects of rhinovirus 39 (RV-39) infection both on the patency and responsiveness of the lower airways. Subjects with allergic rhinitis (AR; n = 50) and without AR (non-AR; n = 46) were intranasally inoculated with RV-39, and monitored for 8 days in an enclosed environment for changes in symptoms, signs, and airway physiology (pulmonary function, bronchial methacholine provocation). All subjects were infected postinoculation. Significant increases in nasal symptoms and secretion weights were observed, with peak effects on days 2-3. Cough was a relatively minor symptom and none of the subjects developed wheezing. Likewise, there were no significant changes in the measured functions of the lower airways. No allergy status effects were observed. Under these experimental conditions, rhinovirus 39 infection did not produce detectable alterations in lower airway function in healthy subjects with and without allergic rhinitis.

Adult↗
PubMed1996

Pattern of nasal secretions during experimental influenza virus infection.

To define the pattern of secretion production during influenza virus infection, 28 adult subjects were inoculated with influenza-A virus (H1N1) and cloistered for a period of 8 days. On each day, symptoms associated with virus infection were scored, nasal secretions were collected and nasal lavages were performed. Recovered lavage fluids were submitted for virus culture and assayed for proteins, histamine, and bradykinin. Twenty-one subjects were infected with influenza-A virus and had significant increases in daily secretion weights and symptom scores extending from day 2 to 7, post-inoculation. Plasma-derived proteins in the nasal lavage fluids showed an early increase to peak at day 4 and then decreased. Glandular proteins showed a later increase to peak at day 5. Bradykinin but not histamine was significantly elevated and tracked the changes in the glandular proteins. In contrast, a shallow increase in symptoms confined to day 2 post-inoculation, but no increase in daily secretion weights was documented in the seven uninfected subjects. There, an increase in plasma proteins was observed on days 1 and 2, but no change in glandular proteins was obvious. These results support a biphasic secretory response during influenza-virus infection with transudation dominating the early period and glandular secretions contributing later.

Adult↗
PubMed1996

A role for the sodium, potassium adenosine triphosphatase (Na+,K+ ATPase) enzyme in degranulation of rat basophilic leukaemia cells.

BACKGROUND: A circulating inhibitor of the sodium, potassium adenosine triphosphatase (Na+,K+ ATPase) enzyme has been described in allergic subjects. Recent studies have suggested that the Na+,K+ ATPase, enzyme may be involved in the signal transduction pathways of various cell types and that inhibition of its activity can modulate histamine release from basophils and mast cells. OBJECTIVE: The purpose of this study was to determine if modulation of Na+,K+ ATPase activity alters degranulation in the 2H3 subline of rat basophilic leukaemia cells (RBL-2H3), a mucosal mast cell model bearing high-affinity Fc receptors for IgE. METHODS: Degranulation was measured by the release of both exogenous serotonin and endogenous histamine. Na+,K+ ATPase activity was assessed by ouabain-sensitive [86rubidium] uptake ([86Rb] uptake) and ex situ enzyme activity. RESULTS: Ouabain-sensitive [86Rb] uptake and degranulation increased in parallel and in a dose-response fashion with increasing Fc receptor cross-linking. Additionally, incubation with ouabain, a known inhibitor of Na+,K+ ATPase activity, decreased both anti-IgE and calcium ionophore-induced degranulation, but increased spontaneous degranulation, each in a dose-response manner. Moreover, the effect of ouabain on degranulation was reversed by rinsing and mimicked by other known inhibitors of Na+,K+ ATPase activity. Finally, in the absence of anti-IgE or calcium ionophore, stimulation of ouabain-sensitive [86Rb] uptake by the sodium (Na+) ionophore monensin was associated with a corresponding dose-response increase in ouabain-sensitive degranulation. These experiments demonstrate that ouabain-sensitive [86Rb] uptake increases following IgE receptor cross-linking in RBL-2H3, and that factors which modulate Na+,K+ ATPase activity in these cells may also regulate degranulation. CONCLUSION: The results of this study suggest an important role for Na+,K+ ATPase activation in the signal transduction pathway of stimulated RBL-2H3.

Animals↗
PubMed1995

State and trait negative affect as predictors of objective and subjective symptoms of respiratory viral infections.

State and trait negative affect (NA) were measured in healthy people immediately before an illness was induced through exposure to a respiratory virus. State NA, disease-specific health complaints (e.g., runny nose, congestion, and sneezing), and an associated objective marker of disease severity (mucus secretion weights) were assessed daily during the illness. Baseline trait and state NA were both associated with increased numbers of subsequent complaints. Although greater numbers of complaints among people high in state NA were explicable in terms of greater disease severity, the association of trait NA and symptoms was independent of objective disease. The trait NA complaint association was also independent of state NA and hence not attributable to trait-elicited state affect. Greater trait NA was associated with biases in complaining during but not before illness. This suggested failure to discriminate between symptoms rather than increased sensitivity or hypochondriacal response.

Adolescent↗
PubMed1995

Influenza A virus--induced acute otitis media.

To better understand the significance of viral upper respiratory tract infections in the pathogenesis of acute otitis media (OM), 27 adults underwent intranasal inoculation with influenza A virus. Monitoring consisted of antibody titer determination, tympanometry, and otoscopy. Microbiologic analysis consisted of cultures and polymerase chain reaction (PCR)-based detection for influenza A virus, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. All subjects became infected with the challenge virus. By day 4, 16 (59%) developed middle ear pressures of -100 mm H2O or below and 4 (25%) of them developed OM. One subject (4%) developed purulent OM requiring myringotomy for pain relief. Middle ear effusion cultures were negative. PCR analysis of that subject's middle ear effusion and nasal washes were positive for influenza A virus and S. pneumoniae. These findings support a causal role for viral upper respiratory tract infections in the pathogenesis of OM, possibly mediated by middle ear underpressures and viral and bacterial middle ear infection.

Acute Disease↗