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Biomedical subjects

E R Bleecker

Publications and source records attributed to E R Bleecker.

At least 55 records · Page 3Linked to original sources
PubMed1997

Sequential effects of aerobic exercise training and weight loss on risk factors for coronary disease in healthy, obese middle-aged and older men.

The relative benefits of weight loss (WL) versus aerobic exercise training (AEX) on cardiac risk factors in obese individuals remain controversial. In this study, we examined the effects of the sequential interventions of 9 months of AEX followed by weight loss with continued AEX (AEX + WL) on cardiac risk factors in 21 obese (body fat, 29.5% +/- 0.8%, mean +/- SEM) middle-aged and older men. AEX increased the maximal aerobic capacity ([VO2max] in liters per minute) of these men by 14% (P < .001), with no significant change in weight. AEX did not improve blood pressure (BP) or oral glucose tolerance, and had no significant effect on lipid concentrations. During the AEX + WL intervention, the 21 men lost 8.1 +/- 0.6 kg. Despite continued training, there was no further increase in VO2max during this intervention. Compared with AEX, AEX + WL decreased glucose and insulin responses during the oral glucose tolerance test (OGTT) by 8% (P < .05) and 30% (P < .01), respectively. AEX + WL reduced plasma triglyceride (TG) by 17% (P < .05) and low-density lipoprotein cholesterol (LDL-C) by 8% (P < .01) and increased high-density lipoprotein cholesterol (HDL-C) by 11% (3.7 mg/dL, P < .01). The sequential interventions resulted in a 20% decrease in the LDL-C/HDL-C ratio. The results demonstrate that AEX + WL had a more substantial impact than AEX alone on glucose tolerance and lipoprotein concentrations. Physicians should encourage obese patients to become physically active and lose weight to improve their cardiac risk factor profile.

Aging↗
PubMed1997

Bronchoalveolar macrophage CD14 expression: shift between membrane-associated and soluble pools.

The bacterial endotoxin [lipopolysaccharide (LPS)]-binding protein CD14 modulates the host response to LPS, but membrane-associated and soluble forms of the molecule exert different biological effects. CD14 anchored to the mononuclear phagocyte membrane (mCD14) enhances response to LPS. Soluble CD14 (sCD14) may block LPS stimulation of CD14-bearing cells while supporting LPS presentation to non-CD14-bearing cells. We analyzed cell mCD14 and sCD14 expression in simultaneously collected human bronchoalveolar macrophages (BAM) and peripheral blood monocytes (PBM). Expression of mCD14 in freshly isolated BAM was only 9% as high as in PBM. Levels of sCD14 in 48 h in BAM culture supernatants were 19% as high as in PBM cultures. Interleukin (IL)-6 increased CD14 expression in both BAM and PBM but exerted different effects on CD14 distribution in these cell types. IL-6 increased only sCD14 release (2.5-fold) in BAM while increasing only mCD14 expression (2.5-fold) in PBM. IL-4 reduced both mCD14 (> 40%) and sCD14 (> 60%) expression in both cell types. We speculate that the balance between sCD14 and mCD14 expression influences the response to aspirated or inhaled LPS in the bronchoalveolar compartment. Cytokine expression and monocyte recruitment may influence this process by modulating CD14 expression.

Adult↗
PubMed1997

Adult patients may outgrow their asthma: a 25-year follow-up study.

The present study investigated the outcome of asthma in a population of 181 adult patients 13 to 44 yr of age (median, 24 yr) who were extensively tested between 1962 and 1970 and in whom asthma was diagnosed. When retested 25 yr later, 38 subjects (21%) did not show bronchial hyperresponsiveness (BHR)(PC20 > 16 mg/ml), 45 subjects (25%) showed a FEV1 > 90% predicted, and 72 subjects (40%) did not report pulmonary symptoms. When absence of asthma was defined as no BHR, FEV1 > 90% predicted, and the absence of pulmonary symptoms reported by the patient, 20 subjects (11%) were no longer considered asthmatic when retested. Absence of asthma after 25 yr was associated with a younger age and less severe airway obstruction at first testing, odds ratios (OR) being 0.36 for age/10 yr, and 1.42 for FEV1/height2 (dl/m2). Absence of BHR was associated with a younger age, a higher FEV1, and a shorter untreated period (years between onset of asthma symptoms and specialized treatment of the disease) at first testing, and a lower total serum IgE level (IU/L) at second testing (OR, 0.48 for age/10 yr; OR, 1.37 for FEV1/height2; OR, 0.93 for untreated period; OR, 0.33 for log [IgE]). Neither sex nor atopy (one or more positive skin tests) were significant determinants of the outcome of both asthma and BHR. Our results suggest that in a substantial proportion of symptomatic asthmatics the disease improved, and that subsets may outgrow their asthma, even in adulthood. The data lend indirect support to the hypothesis that milder disease and earlier intervention are important for a beneficial outcome of asthma.

Adolescent↗
PubMed1997

Evidence for multiple genetic susceptibility loci for asthma.

Genetic susceptibility to asthma is due to multiple genes that interact with each other and the environment. There are many known environmental influences, such as viral and other respiratory infections and exposure to allergens, air pollutants, and active or passive cigarette smoke (1). Genome-wide screens for asthma and atopy have been completed and show statistical evidence for linkage in different racial groups and population samples (4, 5). Some of these linkages have already been replicated in different studies, and most of them are in chromosomal regions containing relevant candidate genes that may regulate inflammatory processes including cytokine synthesis, T-cell responses, or other immune functions. These associations support the relevance of this genetic approach in understanding susceptibility to and expression of asthmatic and allergic phenotypes. Once specific sequence variants are identified, it will become important to test for gene-environment interaction in order to understand the significance and relative effect of each gene on the overall phenotype.

Asthma↗
PubMed1997

Asthma training in third-year medical students.

To assess the educational experiences of physicians-in-training with asthma patients, we had medical students complete asthma surveys at the beginning and end of their internal medicine clerkship (IMC). At the beginning of the IMC, all students received a 1-hr asthma lecture and half of the students received a compilation of pocket cards containing many of the algorithms from the National Heart, Lung, and Blood Institute asthma guidelines. We found that students had relatively few encounters with asthmatic patients during the IMC. Students were good judges of asthma severity but performed poorly on survey questions pertaining to asthma treatment. Confidence in treating and assessing patients improved by the end of the IMC, but remained low. We conclude that the usual 1-hr lecture and limited contact with asthma patients during the IMC may be in adequate to train students to care for patients with asthma.

Adult↗
PubMed1996

Restricted T-cell antigen receptor repertoire in bronchoalveolar T cells from normal humans.

The repertoire of variable alpha (AV) and beta (BV) TCR genes was compared in the peripheral blood and BAL fluid of five healthy individuals. Rearranged TCR transcripts were amplified by a reverse transcription-polymerase chain reaction, using oligonucleotide primers specific for 22 AV and 24 BV gene families. Nearly all AV and BV gene families were expressed in BAL T cells at levels similar to those in blood T cells. The diversity of AV and BV gene repertoire was examined further, testing the distribution of nucleotide lengths of TCR junctional regions. Most V gene families had a normal distribution of junctional region lengths in both blood and BAL T cells. Some gene families, particularly AV21 and BV9 in BAL samples, had a skewed banding pattern, with fewer bands or predominance of several bands. The limited diversity in TCR junctional region lengths was more prominent in CD8+ T cells from BAL fluids than from blood. CD4+ T cells also contributed to the limited diversity in BAL T cells. The oligoclonal expansion of bronchoalveolar CD8+ T cells was confirmed by sequence analysis of AV21-constant alpha (AC) and BV9-BC junctional regions in the blood and BAL cells. The levels of V gene expression and the diversity of junctional region lengths were very similar in T cells obtained from three separate lobes of one donor. In general, skewed patterns of TCR junctional region lengths were not consistent over time two donors, over periods of 3 and 17 months. Together, these data show that the T-cell repertoire is diverse within the lungs of normal humans, except for an oligoclonal predominance of a few V gene families in both CD4+ and CD8+ T cells. The T-cell repertoire in the lungs changes over time, which may reflect environmental exposures.

Adolescent↗
PubMed1996

Asthma and endotoxin: lipopolysaccharide-binding protein and soluble CD14 in bronchoalveolar compartment.

In allergic asthma, inhalation of antigen provokes an early increase in microvascular permeability with protein extravasation and a delayed recruitment of inflammatory cells. We showed that similar concentrations of lipopolysaccharide (LPS) are present in bronchoalveolar lavage fluid (BALF) in 12 subjects without asthma (86.5 +/- 53.8 pg/ml) and 12 subjects with mild asthma (111 +/- 37.0 pg/ml). These LPS levels are insufficient to stimulate cytokine release without accessory molecules. BALF obtained 24 h after segmental ragweed antigen challenge in 11 asthmatics allergic to ragweed contained increased levels of two LPS accessory molecules compared with preantigen BALF, 158-fold more LPS-binding protein (LBP) 4.83 +/- 2.02 vs. 742 +/- 387 ng/ml; P < 0.03) and 31.6-fold more soluble CD14 (sCD14) (3.45 +/- 1.04 vs. 110 +/- 51.6 ng/ml; P < 0.02). Postantigen BALF enhanced binding of fluorescein-conjugated LPS to CD14-bearing THP-1 cells and supported LPS-induced non-CD14-bearing endothelial cell expression of intercellular adhesion molecule-1 and interleukin-6, indicating functional LBP and sCD14. We suggest that extravasation of LBP and sCD14 into the bronchoalveolar compartment after antigen inhalation may enhance the capacity of inhaled or aspirated LPS to activate an inflammatory cascade that may amplify the inflammatory response to inhaled antigen in some asthmatics.

Acute-Phase Proteins↗
PubMed1996

Inhibition of exercise-induced bronchospasm by zileuton: a 5-lipoxygenase inhibitor.

Recent evidence suggests that leukotrienes may have a causative role in exercise-induced asthma. Twenty-four subjects with exercise-induced asthma received either 600 mg zileuton, a 5-lipoxygenase inhibitor, or a placebo four times daily for 2 d prior to exercise challenge (a total of nine doses). The last dose was administered in the laboratory 2 h before the exercise challenge. There was no bronchodilation after nine doses of the 5-lipoxygenase inhibitor (p=0.95). The administration of zileuton inhibited bronchospasm after exercise challenge by 40.75% as compared with placebo. Five minutes after the completion of exercise, the zileuton group's FEV1 was 85.76% of the preexercise value, compared with 73.92% of the preexercise value in the placebo group (p<0.01). The maximum percent change in baseline FEV1 after zileuton was a 15.58% decrement from the preexercise level, as compared with a 28.1% decrease after placebo (p<0.001). Five minutes after exercise, the FVC after zileuton was 92.76% of the preexercise value, as compared with 86.26% after placebo (p<0.05). This is the first study in which a 5-lipoxygenase inhibitor has been shown to attenuate exercise-induced asthma. These results suggest that leukotrienes are important biochemical mediators in the development of exercise-induced bronchospasm, and that leukotriene inhibit may have a role in the treatment of this disorder.

Adult↗
PubMed1996

Clinical effects of nedocromil sodium on allergen-related mechanisms.

Many studies have demonstrated the ability of nedocromil sodium to block the acute response to allergen in persons who are sensitive to allergen. One study with subjects sensitive to ragweed showed a significant protective effect after a single 4 mg dose of nedocromil sodium, with no further protection achieved at higher doses. Numerous studies have also shown the ability of the drug to reduce or abolish the late asthmatic response in sensitive subjects when it was given before allergen challenge. Nedocromil sodium has also been shown to prevent the subsequent development of bronchial hyperresponsiveness. In addition, nedocromil sodium prevented the late asthmatic response when given after allergen challenge and an intact early response. These findings suggest that nedocromil sodium may be preventing the inflammatory events initiated by mast cell mediator and cytokine release.

Acute-Phase Reaction↗
PubMed1996

Mechanisms of asthma.

In recent years, our understanding of basic mechanisms of asthma has increased significantly. This article reviews three specific areas that have been the focus of current asthma research: the role of nitric oxide in the control of airway tone and inflammation, mechanisms of exercise-induced asthma, and current studies in the genetics of asthma. Recent advances in each of these areas have contributed to a better understanding of the pathophysiologic mechanisms in asthma and are important in the diagnosis and therapy of this disease.

Asthma↗
PubMed1995

Effects of weight loss vs aerobic exercise training on risk factors for coronary disease in healthy, obese, middle-aged and older men. A randomized controlled trial.

OBJECTIVE: To compare the effects of weight loss vs aerobic exercise training on coronary artery disease risk factors in healthy sedentary, obese, middle-aged and older men. DESIGN: Randomized controlled trial. SUBJECTS: A total of 170 obese (body mass index, 30 +/- 1 kg/m2 [mean +/- SEM]), middle-aged and older (61 +/- 1 years) men. INTERVENTIONS: A 9-month diet-induced weight loss interventions, 9-month aerobic exercise training program, and a weight-maintenance control group. MAIN OUTCOME MEASURES: Change in body composition, maximal aerobic capacity (V02 max), blood pressure, lipoprotein concentrations, and glucose tolerance. RESULTS: Forty-four of 73 men randomized to weight loss completed the intervention and had a 10% mean reduction in weight (- 9.5 +/- 0.7 kg; P < .001), with no 22 change in VO2 max. Forty-nine of 71 men randomized to aerobic exercise completed the intervention, increased their VO2 max by a mean of 17% (P < .001), and did not change their weight, whereas the 18 men who completed in the control group had no significant changes in body composition or VO2 max. Weight loss decreased fasting glucose concentrations by 2%, insulin by 18%, and glucose and insulin areas during the oral glucose tolerance test (OGTT) by 8% and 26%, respectively (P < .01). By contrast, aerobic exercise did not improve fasting glucose or insulin concentrations or glucose responses during the OGTT but decreased insulin areas by 17% (P < .001). In analysis of variance, the decrement in fasting glucose and insulin levels and glucose areas with intervention differed between weight loss and aerobic exercise when compared with the control group (P < .05). Similarly, weight loss but not aerobic exercise increased high-density lipoprotein cholesterol levels (+ 13%) and decreased blood pressure compared with the control group. In multiple regression analyses, the improvement in lipoprotein and glucose metabolism was related primarily to the reduction in obesity. CONCLUSIONS: These results suggest that weight loss is the preferred treatment to improve coronary artery disease risk factors in overweight, middle-aged and older men.

Aged↗
PubMed1995

Genetic susceptibility to asthma--bronchial hyperresponsiveness coinherited with a major gene for atopy.

BACKGROUND: Bronchial hyperresponsiveness, a risk factor for asthma, consists of a heightened bronchoconstrictor response to a variety of stimuli. The condition has a heritable component and is closely related to serum IgE levels and airway inflammation. The basis for these relations is unknown, as is the mechanism of genetic susceptibility to bronchial hyperresponsiveness. We attempted to define the interrelation between atopy and bronchial hyperresponsiveness and to investigate the chromosomal location of this component of asthma. METHODS: We studied 303 children and grandchildren of 84 probands with asthma selected from a homogeneous population in the Netherlands. Ventilatory function, bronchial responsiveness to histamine, and serum total IgE were measured. The association between the last two variables was evaluated. Using analyses involving pairs of siblings, we tested for linkage between bronchial hyperresponsiveness and genetic markers on chromosome 5q31-q33, previously shown to be linked to a genetic locus regulating serum total IgE levels. RESULTS: Serum total IgE levels were strongly correlated (r = 0.65, P < 0.01) in pairs of siblings concordant for bronchial hyperresponsiveness (defined as a > or = 20 percent decrease in the forced expiratory volume in one second produced by histamine [threshold dose, < or = 16 mg per milliliter]), suggesting that these traits are coinherited. However, bronchial hyperresponsiveness was not correlated with serum IgE levels (r = 0.04, P > 0.10). Analyses of pairs of siblings showed linkage of bronchial hyperresponsiveness with several genetic markers on chromosome 5q, including D5S436 (P < 0.001 for a histamine threshold value of < or = 16 mg per milliliter). CONCLUSIONS: This study demonstrates that a trait for an elevated level of serum total IgE is coinherited with a trait for bronchial hyperresponsiveness and that a gene governing bronchial hyperresponsiveness is located near a major locus that regulates serum IgE levels on chromosome 5q. These findings are consistent with the existence of one or more genes on chromosome 5q31-q33 causing susceptibility to asthma.

Adolescent↗