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Biomedical subjects

C H Bosken

Publications and source records attributed to C H Bosken.

16 recordsLinked to original sources
PubMed2001

Sensitivity to DNA damage induced by benzo(a)pyrene diol epoxide and risk of lung cancer: a case-control analysis.

Levels of DNA adducts vary greatly in vivo, attributable to individual differences in enzymatic bioactivation of benzo(a)pyrene. We developed an assay to measure the levels of DNA adducts induced in vitro by benzo(a)pyrene diol epoxide (BPDE), a bioactivated form of benzo(a)pyrene. In this large molecular epidemiological study of lung cancer, we tested the hypothesis that the level of in vitro BPDE-induced adducts is associated with risk of lung cancer. This hospital-based case-control study included 221 newly diagnosed lung cancer cases and 229 healthy controls frequency matched on age, sex, ethnicity, and smoking status. Short-term cultured peripheral blood lymphocytes from each subject were exposed in vitro to BPDE (4 microm) for 5 h, and the 32P-postlabeling method was then used to measure BPDE-induced DNA adducts in the host cells. Overall, the patients had significantly higher levels of BPDE-DNA adducts than did the controls (mean +/- SD per 107 nucleotides, 93.2+/-89.3 for cases versus 63.7+/-61.1 for controls; P = 0.001). Univariate and multivariate logistic regression analyses were performed to calculate the crude and adjusted odds ratios and their 95% confidence intervals. When the median adduct level of controls (46/10(7) nucleotides) was used as the cutoff point, 64% of cases had higher levels (odds ratio, 2.15; 95% confidence interval, 1.39-3.33, adjusted for age, sex, ethnicity, body mass index, recent weight loss, pack-years smoked, smoking in the last 24 h, and family history of cancer). Stratified analyses showed consistently higher levels of BPDE-induced adducts in cases than in controls, regardless of subgroup of age, sex, ethnicity, body mass index, recent weight loss, pack-years smoked, smoking in the last 24 h, and family history of cancer. A significant dose-response relationship between the quartile levels of BPDE-induced DNA adducts and the risk of lung cancer was observed (trend test, P < 0.001). The significant association between the level of in vitro BPDE-induced DNA adducts and risk for lung cancer suggests that subjects very sensitive to BPDE-induced DNA damage may have a suboptimal ability to remove the BPDE-DNA adducts and so are susceptible to tobacco carcinogen exposure and, therefore, may be at increased risk of lung cancer.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed2001

Adaptations of linkage and association methods for the study of asthma, a complex trait.

Early studies that found significant linkage between markers on 5q and asthma and IgE have not been reproduced. In an attempt to improve the power of these studies we performed a variance components linkage analysis and transmission-disequilibrium tests (TDT) with haplotypes using markers on 5q, using the Southampton and Perth data sets supplied by GAW. The linkage analysis with covariates revealed a maximum lod of 1.57 in the Perth families. The addition of age and RAST significantly improved the fit of the null models but did not improve the lod scores. The TDT tests showed a marginally significant association with D5S393 and D5S399 and with three markers together (IL9, IL4, D5S393). We conclude that further studies are needed to delineate the environmental contribution to this disease so that the genetic factors can be more easily identified. In addition, haplotype analysis may help to identify specific genetic effects.

Adolescent↗
PubMed2000

A parental history of asthma is a risk factor for wheezing and nonwheezing respiratory illnesses in infants younger than 18 months of age.

The relationship between respiratory infection and allergy as risk factors for the development of wheezing illnesses in infants has been in dispute. We hypothesized that a parental history of allergic diseases would be associated with an increased rate of respiratory infections as well as an increased rate of wheezing during infectious episodes. We prospectively evaluated 1,193 infants from birth to 18 mo of age, using bi-weekly telephone surveillance to document all respiratory events. The overall rate of respiratory illness (all RI) increased to a maximum of 10.6 illnesses/infant/year in the 7- to 9-mo age group and then leveled off in the older infants. Multivariable models adjusting for demographic variables, breast feeding, month of illness, number of siblings, and attendance at day care showed an increase in the rate of all RI in infants older than 7 mo of age who had a parental history of asthma (OR = 1.24, CI = 1.09 to 1.41) or a parental history of atopy (OR = 1.14, CI = 1.03 to 1.26). The rate of lower respiratory illnesses accompanied by wheezing was related only to a parental history of asthma (OR = 2.06, CI = 1.36 to 3.11). We conclude that all RI, most of which represent viral infections, are increased in otherwise normal infants with a parental history of asthma or atopy, whereas wheezing is related only to a parental history of asthma.

Asthma↗
PubMed1993

Small airways dimensions in asthma and in chronic obstructive pulmonary disease.

The purpose of this study was to compare the dimensions of the peripheral airways in fatal asthma with those from patients with nonfatal asthma, mild COPD, and normal lung function. Lung specimens from eight individuals who had fatal asthmatic attacks were obtained at postmortem and compared with similar specimens from three asthmatic patients who died of an unrelated cause and four specimens obtained from known asthmatic patients who required lung resection for tumor. These 15 asthmatic lungs were also compared with lungs resected for peripheral neoplasms from 15 patients with normal airway function (FEV1, % of predicted > 85) and 15 patients with mild chronic airflow obstruction (FEV1, % of predicted < 85). All membranous airways with a long-short diameter ratio of 3:1 or less were examined. The smooth muscle and the tissue areas external and internal to the muscle layer were traced using a Bioquant BQ System 4. The same system was used to evaluate the fraction of the submucosa and adventitia taken up by blood vessels. The adventitial, submucosal, and muscle area of the asthmatic airways were greater than those of COPD and control (p < 0.01), and the muscle area was greater in COPD than in control lungs (p < 0.05). These parameters were also greater in the 8 patients with fatal asthma compared with the 7 patients with nonfatal asthma (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Characterization of the inflammatory reaction in the peripheral airways of cigarette smokers using immunocytochemistry.

Lung tissue from 20 patients undergoing resection for a peripheral carcinoma was studied using monoclonal antibodies to identify inflammatory cell types in the peripheral airways and to determine the location of the bronchial-associated lymphoid tissue (BALT). The patients were grouped according to their percent predicted FEV1 (%FEV1) into obstructed (%FEV1 less than 80%) and control (%FEV1 greater than 80%). The resected lungs were filled with dilute cryoembedding media (Tissue-Tek R), frozen over liquid nitrogen, sliced into 2-cm sagittal slices using a band saw, and sampled using a cork bore. Ten serial histologic sections cut from these samples were stained with monoclonal antibodies for specific inflammatory cell types, which were counted and expressed per square millimeter of airway wall area. The results showed that the patients with airway obstruction had more B-lymphocytes in the airway adventitia than did the control subjects (p less than 0.001) and that the number of submucosal polymorphonuclear leukocytes is related to the amount smoked (p less than 0.02). They also show the BALT has a different distribution in human than in rodent lungs in that the lymphoid collections are found in the outer walls of the airway rather than in the submucosa.

Aged↗
PubMed1991

Neutrophil kinetics during active cigarette smoking in rabbits.

Polymorphonuclear leukocyte (PMN) transit through the pulmonary vasculature is slowed during inhalation of cigarette smoke in humans. This study was undertaken to determine the localization of the delayed PMN and whether they release granule-bound enzymes during smoke exposure. Anesthetized New Zealand White rabbits were exposed to cigarette smoke (n = 5) or sham (n = 5) for 10 min while they breathed spontaneously. The cardiac output, pulmonary blood volume and flow, and PMN retention were measured in each of five gravity-defined slices of lung. In three smoke-exposed and three sham animals the lungs were prepared for autoradiography, and the distribution of the radiolabeled PMN was determined. Plasma was assayed for myeloperoxidase in 10 animals. We found that smoke exposure caused increased PMN retention in the top two slices of the lungs without changing hemodynamics. The PMN were randomly distributed in the lobule, and plasma myeloperoxidase was elevated at the beginning of the exposure. We conclude that cigarette smoke may damage the lung by activating PMN in the pulmonary capillary bed.

Animals↗
PubMed1990

Small airway dimensions in smokers with obstruction to airflow.

The obstruction to airflow that develops in some cigarette smokers is thought to be related to inflammation of small airways. However, the mechanism by which inflammation leads to obstruction has not been elucidated. We performed morphometry to determine if the airways of patients with obstruction were thicker than normal. Sixty smokers were selected from those undergoing resectional lung surgery. They were grouped according to their FEV1/FVC ratio (FEV1% control = 77%, FEV1 obstructed = 55%) and matched for age, sex, and height. Wall area (mm2), perimeter (mm), and diameter (mm) were measured by a modification of the technique of James and coworkers (7). The relaxed luminal diameter (mm) and wall thickness (mm) were calculated from these values. A pathology score for inflammation and fibrosis was assigned to each patient, and the percentage of the wall made up of muscle, epithelium, and connective tissue was determined by point counting. Two hundred airways, 90% of which were membranous bronchioles, were measured in each group. The mean-measured luminal diameter in the controls was 0.81 mm and in the obstructed patients 0.70 mm (p less than or equal to 0.05). The regression lines relating wall thickness to calculated luminal diameter showed that the airways of the obstructed patients were thicker throughout the size range measured (p less than or equal to 0.005). The muscle, epithelium, and connective tissue were all increased in the obstructed patients (p less than or equal to 0.001). In addition, the wall thickness correlated with the pathology score (r = 0.6074, p less than or equal to 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Pathologic features of allergic bronchopulmonary aspergillosis.

We describe the pathologic features in surgically excised lung tissue specimens from 18 cases of allergic bronchopulmonary aspergillosis (ABPA). The main abnormalities involved bronchi and bronchioles. All cases showed bronchocentric granulomatosis (BCG), mucoid impaction of bronchi (MIB), or both. The impacted mucin of MIB contained large numbers of eosinophils and Charcot-Leyden crystals. A distinctive exudative bronchiolitis was present distal to areas of BCG in 13 cases. This lesion was characterized by filling of bronchiolar lumens with necrotic neutrophils and eosinophils in a basophilic mucinous exudate. A peribronchiolar chronic inflammatory infiltrate was seen in 15 cases; eosinophils were prominent in 10 of these cases. Foci of eosinophilic pneumonia were seen in 13 cases, and noninvasive fungal hyphae were identified in 14. We conclude that the finding of BCG or MIB, or a combination of both, especially in conjunction with tissue eosinophilia, should suggest the diagnosis of ABPA. When noninvasive fungal hyphae are also present, the changes are diagnostic of ABPA or a related allergic fungal reaction.

Adolescent↗
PubMed1987

Effects of hypohydration on lung functions in humans.

We studied lung function tests during euhydration (Days 1 and 2), hypohydration (Days 3 and 4), and rehydration (Days 5, 6, and 7) in 6 normal subjects. Hypohydration was induced by administering chlorthalidone, and this resulted in a 4.5% loss of body weight. During hypohydration, lung volumes increased significantly. Interestingly, ventilatory lung function tests including peak expiratory flow rate, FEV1, maximal voluntary ventilation, and flow rates at low lung volumes also increased significantly and returned to normal upon rehydration. Diffusing capacity for carbon monoxide remained unchanged. The improvement in ventilatory lung function tests during hypohydration was surprising, and it is suggested that this was related to loss of water within and/or around the airways. This mechanism is opposite to that which occurs in pulmonary edema with excess lung water where reduction in flow rates occurs.

Adult↗
PubMed1984

Comparison of gallium-67 scanning, bronchoalveolar lavage, and serum angiotensin-converting enzyme levels in pulmonary sarcoidosis. Predicting response to therapy.

Patients with active pulmonary sarcoidosis underwent bronchoalveolar lavage, gallium scan, and serum angiotensin-converting enzyme (ACE) level determination prior to treatment with corticosteroids. Pulmonary function was tested before and after therapy. Increase in vital capacity after treatment ranged from 40 to 1,030 ml; 12 of the 16 patients studied had an increase of more than 200 ml. There was a close correlation between the percentage uptake of gallium scan and the increase of the vital capacity after therapy (r = 0.95, p less than 0.01). There was no relationship between the percentage of lymphocytes obtained on lavage and the changes in vital capacity with therapy (r = 0.05). There was a positive correlation between the changes in vital capacity and the ratio of T4(+):T8(+)lymphocytes (r = 0.62, p less than 0.05) and number of T4 (+) lymphocytes (r = 0.92, p less than 0.01) in the bronchoalveolar fluid. There was a low correlation between the pretreatment ACE level and the change in vital capacity (r = 0.368, p greater than 0.05).

Acetylcholinesterase↗
PubMed1984

Right and left ventricular function at rest and with exercise in patients with sarcoidosis.

Fourteen patients with restrictive pulmonary disease due to sarcoidosis were studied with radionuclide angiocardiography in order to define the incidence and significance of right and left ventricular dysfunction. Right and left ventricular ejection fractions were determined by an equilibrium technique at both rest and exercise. All patients had a normal left ventricular ejection fraction with rest and 12 of 14 had the normal 5 percent or greater rise in ejection fraction with exercise. The right ventricular ejection fraction was abnormal in three patients at rest and only two patients had a 5 percent or greater rise in ejection fraction with exercise. A correlation was found between the right ventricular ejection fraction with exercise and the total lung capacity (r = 0.73, p less than 0.01) and the arterial PO2 during exercise (r = 0.74, p less than 0.01).

Adult↗
PubMed1983

Quantitation of bronchoalveolar lavage with methylene blue.

Bronchoalveolar lavage yields a return that is composed of lung liquid and lavage liquid in variable and unknown proportions. Concentrations of chemicals and cells in lung liquid have been presented by previous workers in relative terms, sometimes relating them to the albumin content on the assumption that it is comparatively stable. We report here the use of methylene blue in the introduced fluid as an external marker. This allows the dilution, and thus absolute values, to be calculated. We found the concentrations of albumin in lung fluid to be significantly higher in a group of patients with sarcoidosis (0.50 mg/ml +/- 0.40, mean +/- standard deviation) than in a control group (0.15 mg/ml +/- 0.07; p less than 0.02). Absolute cell counts of lymphocytes in lung fluid lavaged from patients with sarcoidosis were higher than those for control patients (154 lymphocytes/ml +/- 98.9 versus 4 +/- 2.6). There was a correlation between the absolute number of lymphocytes and the albumin concentration per milliliter lung liquid (r = 0.71, p less than 0.001).

Adult↗