Bicarbonate and chloride secretion in Calu-3 human airway epithelial cells.

Serous cells are the predominant site of cystic fibrosis transmembrane conductance regulator expression in the airways, and they make a significant contribution to the volume, composition, and consistency of the submucosal gland secretions. We have employed the human airway serous cell line Calu-3 as a model system to investigate the mechanisms of serous cell anion secretion. Forskolin-stimulated Calu-3 cells secrete HCO-3 by a Cl-offdependent, serosal Na+-dependent, serosal bumetanide-insensitive, and serosal 4,4'-dinitrostilben-2,2'-disulfonic acid (DNDS)-sensitive, electrogenic mechanism as judged by transepithelial currents, isotopic fluxes, and the results of ion substitution, pharmacology, and pH studies. Similar studies revealed that stimulation of Calu-3 cells with 1-ethyl-2-benzimidazolinone (1-EBIO), an activator of basolateral membrane Ca2+-activated K+ channels, reduced HCO-3 secretion and caused the secretion of Cl- by a bumetanide-sensitive, electrogenic mechanism. Nystatin permeabilization of Calu-3 monolayers demonstrated 1-EBIO activated a charybdotoxin- and clotrimazole- inhibited basolateral membrane K+ current. Patch-clamp studies confirmed the presence of an intermediate conductance inwardly rectified K+ channel with this pharmacological profile. We propose that hyperpolarization of the basolateral membrane voltage elicits a switch from HCO-3 secretion to Cl- secretion because the uptake of HCO-3 across the basolateral membrane is mediated by a 4,4 '-dinitrostilben-2,2'-disulfonic acid (DNDS)-sensitive Na+:HCO-3 cotransporter. Since the stoichiometry reported for Na+:HCO-3 cotransport is 1:2 or 1:3, hyperpolarization of the basolateral membrane potential by 1-EBIO would inhibit HCO-3 entry and favor the secretion of Cl-. Therefore, differential regulation of the basolateral membrane K+ conductance by secretory agonists could provide a means of stimulating HCO-3 and Cl- secretion. In this context, cystic fibrosis transmembrane conductance regulator could serve as both a HCO-3 and a Cl- channel, mediating the apical membrane exit of either anion depending on basolateral membrane anion entry mechanisms and the driving forces that prevail. If these results with Calu-3 cells accurately reflect the transport properties of native submucosal gland serous cells, then HCO-3 secretion in the human airways warrants greater attention.

Tuberculous meningitis in the southwest United States: a community-based study.

This community-based study analyzed 54 patients with definite or probable tuberculous meningitis (TBM) in New Mexico from 1970 through 1990. Patients ranged in age from 4 months to 86 years. The highest age-specific incidence occurred in the elderly, but 22% of patients were less than 10 years old. Native American patients were overrepresented. Patients were as likely to live in small towns as in large urban cities. Symptoms were present for a median of 13 days before admission. The majority of patients had fevers, headache, stiff neck, and mental changes, such as confusion or lethargy. No patient was admitted comatose. Focal neurologic signs were present in 33%. Laboratory testing found hyponatremia in 79%, pulmonary infiltrates on chest x-ray in 40%, ventricular dilatation on CT or MRI in 52%, and tuberculomas in 16%. PPD skin tests were positive in 64%. CSF cultures grew Mycobacterium tuberculosis in 50%, but colony counts were always lower than 10(2)/ml. As a consequence, acid-fast stains of CSF sediment were reported as positive in only 4%. Six patients were not diagnosed during the hospitalization and died of complications. Twenty-three percent of patients who were appropriately treated also died of complications during the initial hospitalization. Tuberculous meningitis continues to be an important disease in small communities, and affects all ages and ethnic and socioeconomic backgrounds.

Assessing food selection in a health promotion program: validation of a brief instrument for American Indian children in the southwest United States.

OBJECTIVE: Brief dietary assessment instruments are needed to evaluate behavior changes of participants in dietary intervention programs. The purpose of this project was to design and validate an instrument for children participating in Pathways to Health, a culturally appropriate, cancer prevention curriculum. DESIGN: Validation of a brief food selection instrument, Yesterday's Food Choices (YFC), which contained 33 questions about foods eaten the previous day with response choices of yes, no, or not sure. Reference data for validation were 24-hour dietary recalls administered individually to 120 students selected randomly. SUBJECTS: The YFC and 24-hour dietary recalls were administered to American Indian children in fifth- and seventh-grade classes in the Southwest United States. STATISTICAL ANALYSES PERFORMED: Dietary recalls were coded for food items in the YFC and results were compared for each item using percentage agreement and the kappa statistic. RESULTS: Percentage agreement for all items was greater than 60%; for most items it was greater than 70%, and for several items it was greater than 80%. The amount of agreement beyond that explained by chance (kappa statistic) was generally small. Three items showed substantial agreement beyond chance (kappa > or = 0.6); 2 items showed moderate agreement (kappa = 0.40 to 0.59) most items showed fair agreement (kappa = 0.20 to 0.39). The food items showing substantial agreement were hot or cold cereal, low-fat milk, and mutton or chile stew. Fried or scrambled eggs and deep-fried foods showed moderate agreement beyond chances. CONCLUSIONS: Previous development and validation of brief food selection instruments for children participating in health promotion programs has had limited success. In this study, instrument-related factors that apparently contributed to poor agreement between data from the YFC and 24-hour dietary recall were inclusion of categories of foods vs specific foods; food knowledge, preparation, and vocabulary, item length, and overreporting of attractive foods. Collecting and scoring the 24-hour recall data may also have contributed to poor agreement. Further development of brief instruments for evaluating changes in children's behavior in dietary programs is necessary. Factors related to the YFC that need further development may be issues that are also important in the development of effective, brief dietary assessments for children as individual clients or patients.

Body image and weight concerns among Southwestern American Indian preadolescent schoolchildren.

This study was undertaken to determine whether perceptions about body image and size vary by body mass index (BMI) and demographic factors among American Indian children in the Southwestern United States. We surveyed 1,996 American Indian schoolchildren in the fifth grade (mean age 10.5 +/- 0.7 years) at eleven rural elementary schools. Heights and weights were measured using standard protocol. Multiple linear regression models were developed for preferred body shape, desired body shape, and body satisfaction to determine association with demographic and physical factors. Results from multiple linear regression modeling indicated that BMI and gender influence body satisfaction, with heavier children and girls being less satisfied with their bodies (P<.001 and P<.05, respectively). Geographic isolation and lack of amenities in the home did not appear to affect body satisfaction or messages from others about being too fat or thin; however, geographically isolated students were more likely to choose a larger body shape as best looking. Girls of appropriate weight were 2.2 times more likely than boys to have been told they were too fat. Sixty-one percent of all students surveyed had tried to lose weight. These findings, although similar to those for non-Hispanic Whites of the same age, are contrary to prevailing ideas that American Indians value obesity. In fact, we observed a high level of body dissatisfaction among children of appropriate weight, particularly girls, and prevalent dieting across all weight categories and both genders.

Sex steroids, periodontal health, and tooth loss in older men.

Sex steroids have a significant effect on skeletal biology in men, with reduced levels being associated with lower skeletal bone mass and cortical thickness. The purpose of this study was to determine if sex steroids are associated with periodontitis and tooth loss in a cohort of 1210 older dentate men followed for 3 years. Periodontal measures included attachment loss, pocket depth, gingival bleeding, and number of teeth. Baseline serum testosterone and estradiol were measured by radioimmunoassay. Severe periodontitis was common at baseline (38%), and progression occurred in 32% of the cohort. Incident tooth loss occurred in 22% of the cohort. Testosterone, estradiol, and sex hormone binding globulin (SHBG) concentrations were not related to baseline periodontal status or number of teeth. Moreover, there was no relationship between sex steroid levels and periodontitis progression or incident tooth loss. Although periodontitis, progression of periodontitis, and tooth loss are common in older men, they were not associated with sex steroids.

Rate and circumstances of clinical vertebral fractures in older men.

UNLABELLED: We examined the rate of clinical vertebral fractures, and the circumstances associated with the fractures, in a cohort of 5,995 US older men. Fractures were more common in the most elderly men, and were usually associated with falls and other low-energy trauma. INTRODUCTION: Little is known about clinical vertebral fractures in older men. We postulated that clinical vertebral fractures occur with falls, affect men with osteoporosis, and are more common as age increases. METHODS: Five thousand nine hundred and ninety-five men aged > or =65 years were followed prospectively for an average of 4.7 years. Men with incident clinical vertebral fractures were compared to controls. RESULTS: One percent (n = 61) sustained incident clinical vertebral fractures (2.2/1,000 person-years). The rate of fracture rose with age (0.7% in men 65-69 years and 5% > or =85 years). Fractured men were more likely frail (8.2% vs. 2.2%), more often fell (36.1% vs. 21%) and had lower total hip and lumbar spine BMD (all p values < or =0.002). In 73.8% of cases fractures were precipitated by no known trauma or by low-energy trauma, including falls in 57.3% Fractures were thoracic in 33% and lumbar in 56%. Men with an incident vertebral fracture were more likely to be osteoporotic (13% vs. 2%, p < 0.0001), but most men with incident fractures did not have osteoporosis. CONCLUSIONS: Incident clinical vertebral fractures were relatively common in older men and the rate increased after age 80 years. Fractures were usually associated with minimal trauma, most commonly a fall.

Endogenous sex steroids, weight change and rates of hip bone loss in older men: the MrOS study.

INTRODUCTION: Lower levels of endogenous sex steroids or declines in these hormones may contribute to the increased rates of bone loss observed in older adults experiencing weight loss. We hypothesized that among older men with weight loss, higher rates of bone loss at the hip would be observed in men with lower baseline bioavailable sex steroids or those with greater declines in these hormones. METHODS: To test this hypothesis, body weight, hip bone mineral density (BMD) using dual energy x-ray absorptiometry and endogenous sex steroids in paired serum samples by sensitive immunoassays were measured at a baseline and at a second examination that was held an average of 1.8 years later in 1267 older men enrolled in the Osteoporotic Fractures in Men (MrOS) study. RESULTS: Men experiencing weight loss had higher rates of hip bone loss than those with stable weight or weight gain within each quartile of baseline sex steroid level [p values for test of trend across weight change categories <0.010 within each quartile of bioavailable estradiol and testosterone and <0.060 within each quartile of sex hormone-binding globulin (SHBG)]. Results were similar when a change in sex steroids was substituted for baseline sex steroids in the analyses. Among men with weight loss, the rate of decline in total hip BMD showed a stepwise increase in magnitude with decreasing baseline bioavailable estradiol (p value for trend <0.040), with increasing baseline SHBG (p value for trend<0.030) and with greater decreases in bioavailable testosterone from baseline (p value for trend <0.001). CONCLUSIONS: These findings support the hypothesis that the impact of weight loss in older men on rates of hip bone loss may be increased by the presence of a sex steroid insufficiency.

Tobacco use: baseline results from pathways to health, a school-based project for southwestern American Indian youth.

BACKGROUND: This paper describes a school-based cancer prevention project for fifth- and seventh-grade Navajo and Pueblo Indian children living in the Southwest. Baseline data are presented from 714 students who completed questionnaires on smoking and smokeless tobacco. METHODS: Questionnaires were administered in the fifth- and seventh-grade classrooms prior to students receiving the Pathways to Health cancer prevention curriculum. RESULTS: In our sample there were increases from fifth to seventh grade in self-reported current cigarette use and intention to use. Also, boys were more likely to use and intend to use cigarettes than girls. The use of smokeless tobacco also increased with increasing grade level, though this trend was less pronounced for girls. A significant gender difference was found in the use of smokeless tobacco with boys reporting higher use. However, reported use by girls was higher than is typically noted for non-Hispanic white girls. CONCLUSIONS: There is evidence of experimentation and regular use of tobacco products by both Navajo and Pueblo boys and girls. Even more students indicate intention to use tobacco products in the future. These data confirm the need for primary prevention programs designed for this population of American Indians.

Mycoplasma pulmonis inhibits electrogenic ion transport across murine tracheal epithelial cell monolayers.

Murine chronic respiratory disease is characterized by persistent colonization of tracheal and bronchial epithelial cell surfaces by Mycoplasma pulmonis, submucosal and intraluminal immune and inflammatory cells, and altered airway activity. To determine the direct effect of M. pulmonis upon transepithelial ion transport in the absence of immune and inflammatory cell responses, primary mouse tracheal epithelial cell monolayers (MTEs) were apically infected and assayed in Ussing chambers. M. pulmonis-infected MTEs, but not those infected with a nonmurine mycoplasma, demonstrated reductions in amiloride-sensitive Na+ absorption, cyclic AMP, and cholinergic-stimulated Cl- secretion and transepithelial resistance. These effects were shown to require interaction of viable organisms with the apical surface of the monolayer and to be dependent upon organism number and duration of infection. Altered transport due to M. pulmonis was not merely a result of epithelial cell death as evidenced by the following: (i) active transport of Na+ and Cl-, albeit at reduced rates; (ii) normal cell morphology, including intact tight junctions, as demonstrated by electron microscopy; (iii) maintenance of a mean transepithelial resistance of 440 omega/cm2; and (iv) lack of leakage of fluid from the basolateral to the apical surface of the monolayer. Alteration in epithelial ion transport in vitro is consistent with impaired pulmonary clearance and altered airway function in M. pulmonis-infected animals. Furthermore, the ability of M. pulmonis to alter transport without killing the host cell may explain its successful parasitism and long-term persistence in the host. Further study of the MTE-M. pulmonis model should elucidate the molecular mechanisms which mediate this reduction in transepithelial ion transport.