Temporal changes in UK birth order and the prevalence of atopy.

BACKGROUND: Many studies have reported an inverse association between birth order and the risk of respiratory allergic disease. In recent decades, the prevalence of atopy has increased alongside reductions in fertility rates. AIMS OF THE STUDY: To quantitate how much of the increased prevalence of atopy, measured by skin prick test or specific IgE, can be attributed to temporal changes in family size in the United Kingdom. METHODS: Through a systematic literature review (MEDLINE, 1965-2009), five studies of UK populations were identified and their data were included in the calculation of a summary odds ratio for the risk of atopy for each birth order. Information on changes in UK family sizes between 1960 and 2001 was obtained from Eurostat. On this basis, expected increases in the prevalence of atopy were calculated by weighting the proportion in each birth order category for 1960 and 2001 by the summary odds ratio for that category and then calculating the relative risk of atopy in 2001 compared with 1960. RESULTS: The pooled summary odds ratios for atopy were 0.90, 0.69 and 0.69 for those born second, third and fourth (or higher), respectively. The expected relative increase in the prevalence of atopy resulting from a change in family size between 1960 and 2001 was 3%. CONCLUSIONS: Despite the strong associations between birth order and atopy, reductions in family size in the last 40 years account for little of the increase in atopy.

Detergent protease exposure and respiratory disease: case-referent analysis of a retrospective cohort.

OBJECTIVES: To examine the relationship between protease exposure and respiratory disease in a cohort of detergent enzyme manufacturers. METHODS: Case-referent analysis of a cohort of employees working in a European detergent factory between 1989 and 2002. Cases with new lower or upper respiratory disease were ascertained by examination of occupational health records and matched to referents on date of first employment. Personal exposures to airborne detergent protease were estimated, using a job exposure matrix, from >12,000 measurements taken in the factory during the period of study. RESULTS: We found clear, monotonic relationships between estimated protease exposure and both lower and upper respiratory disease. After control for age, sex and smoking, the odds ratio of lower respiratory disease was significantly elevated (1.98, 95% CI 1.04 to 3.79) in those employees working in jobs in the highest quartile of protease exposure (geometric mean 7.9 ng x m(-3)). For employees with upper respiratory disease, the risk was significantly elevated at a lower level of estimated protease exposure (geometric mean 2.3 ng x m(-3)). CONCLUSIONS: These findings provide strong evidence of an association between detergent enzyme exposure and the development of respiratory disease in an occupational setting. Using the routinely collected information on specific sensitisation and the close attention to workplace exposures that are characteristic of this industry, it should be possible to derive meaningful occupational exposure standards for most detergent enzymes.

Promoting weight loss in type II diabetes.

OBJECTIVE: To examine strategies-behavioral therapies, exercise, diet, anorectic drugs, surgery, or a combination of strategies-used for promoting weight loss in people with type II diabetes. RESEARCH DESIGN AND METHODS: Meta-analysis was used to synthesize research of promoting weight loss in the population. Literature search strategies involved reviewing bibliographies, conducting computer searches and surveys of relevant master's degree programs, and contacting representatives of the Centers for Disease Control. The final sample consisted of 89 studies involving 1,800 subjects. Data were extracted on 80 variables characterizing the sample of studies/subjects and on 23 outcome variables, including weight, metabolic control, lipids, and other physiological parameters. RESULTS: Diet alone had the largest statistically significant impact on weight loss (-20 lb) and metabolic control (-2.7% in glycosylated hemoglobin). All diets significantly improved fasting blood sugar. Behavioral programs alone had a statistically significant impact on weight loss (-6.4 lb) and metabolic control (-1.5%) but effects were less than for diet alone. Data from the few exercise studies indicated that weighted average effects for exercise on weight loss (-3.4 lb) and metabolic control (-0.8%) were less than diet alone. Behavioral therapy plus diet plus exercise was associated with statistically significant effect size estimates for weight loss (-8.5 lb) and metabolic control (-1.6%). Diet alone achieved better results. Effects of weight promotion strategies, in general, were smaller in experimental studies and for individuals over age 55. CONCLUSIONS: Dietary strategies are most effective for promoting short-term weight loss in type II diabetes. A number of gaps exist in the extant literature- descriptions of subjects, interventions, or longitudinal outcomes beyond 12 months after intervention.

Heterogeneity of nuclear estrogen-binding sites in the rat uterus: a simple method for the quantitation of type I and type II sites by [3H]estradiol exchange.

Estrogen administration to mature-ovariectomized rats causes the activation or stimulation of secondary nuclear estrogen-binding sites (type II) in the uterus which can interfere with estrogen receptor (type I) measurement. Earlier reports from our laboratory have shown that quantitation of type I sites in the presence of the type II site is very difficult and can only be achieved by graphic analysis of saturation curves which employ a wide range (0.4-40 NM) of [3H]estradiol concentrations in nuclear exchange assay. The studies presented in this manuscript describe simple methods which can be used to separately quantitate both nuclear estrogen-binding sites using a single concentration of [3H]estradiol. Since the nuclear type II site does not bind [3H]estradiol in the presence of reducing agent, type I sites can be easily quantitated by incubating nuclei (37 C for 30 min) in Tris-EDTA buffer containing 0.1-1.00 mM dithiothreitol using a single saturating concentration of [3H]estradiol. Conversely, a single concentration of [3H]estradiol (40-80 nM) can be used to quantitate the nuclear type II site by incubating nuclei in Tris-EDTA buffer under conditions (4 C for 60 min) which do not measure occupied nuclear estrogen receptor. Therefore, by using the appropriate buffer system, type I and type II sites can be easily separated in mixed binding systems. In addition, we also demonstrate that Nafoxidine does not bind to the nuclear type II site. Therefore, it can be used as a competitive inhibitor of [3H]estradiol binding to type I sites and permit the measurement of type II sites without interference from type I sites. These techniques should be applicable to autoradiographic or fluorescence studies which cannot discriminate between steroid binding to these two classes of nuclear estrogen-binding sites.

Symptom-related self-care of Mexican Americans with type 2 diabetes: preliminary findings of the Starr County Diabetes Education Study.

Starr County, Texas, a Texas-Mexico border community, was the site of a study involving culturally-appropriate education and group support for Mexican Americans with type 2 diabetes. Data were collected from 63 subjects on frequency of diabetes-related symptoms during the previous month and on self-care symptom treatments. On average, subjects were 57-year-old females, diagnosed with diabetes for 10 years, and exhibiting HbA1c levels of 12.5%. Almost 50% experienced excessive urination, excessive thirst, shakiness/nervousness, and numbness and/or tingling in their extremities. More than 50% of those who experienced symptoms did not view them as serious. Only one subject checked blood sugar levels when symptoms occurred. Significantly higher mean glycosylated hemoglobin levels were found for individuals who experienced dizziness and/or chest pain compared with those who did not. A variety of self-care treatments were employed, including over-the-counter medications and home remedies.

Nuclear binding of the estrogen receptor: heterogeneity of sites and uterotropic response.

Two kinds of estradiol binding sites are present in purified nuclei from the rat uterus following estradiol injection. One of these sites (type I) corresponds to the well-known estrogen receptor which undergoes translocation from the cytoplasm to the nucleus. The second site (type II) is not translocated from the cytoplasm to the nucleus, however, estradiol treatment does stimulate an increased number of these sites. Type II sites are observed in purified nuclei and chromatin isolated from the uterus but not from non-target tissues such as the spleen and diaphragm. Thus an elevation in the levels of type II sites appear to be a specific nuclear response of the rat uterus to estradiol. Saturation analysis over a wide range of [3H]-estradiol concentrations produces a binding curve for type II sites which is sigmoidal and hence no accurate estimation of the dissociation constant is possible. The binding of [3H]-estradiol to nuclear type II sites is inhibited by estradiol and diethylstilbestrol but not by progesterone, testosterone, or corticosterone. Extraction of nuclei isolated from estrogen treated rat uteri with KCl provides a complex picture. Direct labeling of nuclear estrogen receptors either by in vivo injection or in vitro incubation of intact uteri with [3H]-estradiol measures only a fraction of the specific estrogen binding sites associated with the nuclear pellet following 0.4 M KCl extraction. These sites are more accurately determined by performing saturation analysis over a wide range of [3H]-estradiol concentrations by exchange which measures specific estrogen binding sites, not [3H]-steroid. Saturation analysis of estradiol binding to KCl extracted nuclei when performed by exchange, with appropriate corrections for type II binding, reveals that approximately 1000--2000 receptors per nucleus are resistant to KCl extraction 1 hr after administration. The same numbers of type I sites display long-term nuclear retention. A single injection of estradiol results in long term (greater than 6 h) retention of type I sites, rapid and sustained elevations (1--72h) in type II sites and true uterine growth (uterine wet weight at 24--43 h). Estriol injections caused a rapid increase in nuclear type I sites which was not accompanied by an increase in type II sites and no true uterine growth occurred. Administration of estriol or estradiol as a pellet implant, which causes continuous occupancy of type I sites, increases the quantity of nuclear type II sites and stimulates true uterine growth. Therefore, we conclude that elevated levels of nuclear type II sites correlate with the long term uterotropic response to estrogenic hormones. Although we do not understand the function of this second class of binding sites it is possible that the type II sites represent a major component in the mechanism by which estrogens stimulate growth of the uterus.

Radon progeny as sources of gross-alpha radioactivity anomalies in ground water.

Gross-alpha radiation data from ground water samples are subject to variability introduced as a result of analytical procedure. For example, ground water in the surficial aquifer of central Florida commonly has gross-alpha radioactivity in excess of 555 Bq m-3 (15 pCi L-1). This activity, commonly unsupported by Ra, often results from the 222Rn progeny. The relatively short-lived daughters of 222Rn can give rise to variations in gross-alpha measurements of up to 2 orders of magnitude in replicate samples. Polonium-210, a longer-lived Rn daughter, is also found in concentrations greater than predicted by the Ra content. As a consequence, it is suggested that gross-alpha measurements include Po analyses with Ra and U when standards are exceeded. It should be recognized that, depending on the activity of 210Pb, 210Po activity may vary significantly with holding time. Variations of measured Po activity in replicate samples collected and prepared by present methods indicate that Po analyses may be inconsistent and frequently underestimate total Po activity. Sample preparation methods and measurement techniques are discussed which greatly improve the overall accuracy and consistency of gross-alpha and Po analyses.

Type 2 diabetes in children and adolescents: an emerging disease.

The incidence of type 2 diabetes is increasing in the United States, and minority populations in particular seem to be affected. In the past, it was thought that type 2 diabetes occurred only in adults. However, an alarming epidemic has emerged, and children as young as 8 years of age are now being diagnosed with the disease. The purpose of this article is to present pediatric nurse practitioners with the most recent information about type 2 diabetes in children and adolescents, summarize current understanding about diagnosis, and outline treatment options.

Self-transcendence and activities of daily living. The woman with the pink slippers.

The number of older adults in our population is steadily increasing. Many older adults continue to remain active and care for themselves. However, differences exist in older adults' ability to perform activities of daily living. The purpose of the study was to explore relationships among self-transcendence (ST), health status (SHS), and ability to perform activities of daily living (ADL) in noninstitutionalized older adults. The 88 participants were primarily widowed, White women, 65 years of age and older (M = 73.4), who perceived their health positively, and had 12 years or more of education. Findings included statistically significant relationships between ST and ADL and SHS and ADL. Twenty-two percent of the variance in ability to perform ADL was explained by SHS, and an additional 6% was explained by ST. Nurses are encouraged to explore factors that contribute to older adults' ability to remain independent.

De novo purine synthesis, purine salvage, and DNA synthesis in normal and Lesch-Nyhan fibroblasts infected with Mycoplasma pneumoniae.

The effects of Mycoplasma pneumoniae on host cell metabolism were studied by using two types of host cells, MRC-5 human lung fibroblasts, a normal cell line, and Lesch-Nyhan fibroblasts, a cell line deficient in hypoxanthine-guanine phosphoribosyl transferase (EC 2.4.2.8). The susceptibilities of the two cell types were determined by infecting the cells with M. pneumoniae at different multiplicities of infection (MOI). Our data indicate that the Lesch-Nyhan cells were four times more susceptible to damage by M. pneumoniae than the MRC-5 cells. The effects of different MOIs (10 and 50) on de novo purine synthesis. DNA synthesis, and the development of a cytopathic effect were determined. In both cell types, the higher MOI inhibited de novo purine synthesis to a greater extent than the lower MOI. This correlated closely with the cytopathic effect which developed in the monolayers (i.e., the more the inhibition of de novo purine synthesis, the greater the cytopathic effect which developed). In the Lesch-Nyhan cells, DNA synthesis was completely inhibited by the high MOI, whereas in the MRC-5 cells, DNA synthesis was stimulated by the high MOI. In the MRC-5 cells infected with M. pneumoniae, purine salvage activity increased, as indicated by an increase in adenosine deaminase (EC 3.5.4.4) activity. These data indicate that M. pneumoniae alters host cell metabolism, particularly the nucleic acid metabolic pathways. This may explain in part the mechanism of pathogenesis of M. pneumoniae infection.

Differential cytopathogenicity accompanying Mycoplasma pneumoniae infection of human lung fibroblasts maintained in newborn bovine serum or fetal bovine serum.

MRC-5 human lung fibroblasts maintained in Eagle's basal medium (BME) with either 10% fetal bovine serum (FBS) or 10% newborn bovine serum (NBS) did not respond identically to infection by Mycoplasma pneumoniae. Fibroblasts grown in NBS did not develop any cytopathic effect (CPE) when infected with M. pneumoniae, whereas those maintained in FBS developed a pronounced CPE. There was also a difference in sensitivity to infection for fibroblasts maintained in the two sera before the infection. Fibroblasts maintained in NBS, then transferred to FBS 48 h before infection, were still less sensitive to M. pneumoniae infection than cells maintained constantly in FBS. Mycoplasma pneumoniae attached comparably to the fibroblasts grown in the two sera, so the differences in CPE development could not be attributed to differences in mycoplasma attachment. Measurements of DNA, RNA, and protein syntheses of the fibroblasts grown in NBS and FBS indicate that the cells in NBS were growing more rapidly than those in FBS. A determination of the doubling times shows that the doubling time of cells in NBS was 44 h, whereas that of cells in FBS was 51 h. Polyacrylamide gel electrophoresis of samples of NBS and FBS showed significant differences in serum protein composition. The NBS had several protein bands that were lacking in the FBS. This study demonstrates the importance of serum effects in the study of M. pneumoniae infection.

Alterations in nucleotide content of human lung fibroblasts infected with Mycoplasma pneumoniae.

The nucleotide content of normal MRC-5 human lung fibroblasts and fibroblasts infected with Mycoplasma pneumoniae PI 1428 was determined. Nucleotides from control and infected fibroblasts were extracted with 5% trichloracetic acid. After neutralization of the extracts, the nucleotides in the extracts were separated by anion-exchange chromatography. Significant differences were found between the nucleotide content of the control and infected cells. Nucleotide triphosphate levels were twofold higher in the control fibroblasts than in the infected fibroblasts 4 h after the initiation of infection. At the same time, nucleotide diphosphate and monophosphate levels were higher in the infected fibroblasts than in the control fibroblasts. Determination of the energy charge ratio for each set of nucleotides (adenosine, guanosine, cytidine, and uridine) demonstrated a shift of nucleotide content in the infected fibroblasts. Immediately after infection, the energy charge for each set of nucleotides was higher for the control fibroblasts than it was for the infected fibroblasts. This pattern continued throughout the infection period with only minor exceptions. The work presented here indicates a loss of energy charge in fibroblasts infected with M. pneumoniae and may help to explain some of the metabolic changes and cell damage which accompany infection.

Role of host cell metabolism in the pathogenesis of Mycoplasma pneumoniae infection.

Human lung fibroblasts develop a cytopathic effect (CPE) when infected with Mycoplasma pneumoniae. This study was designed to determine the relationship between host cell metabolism and the formation of the CPE. Human lung fibroblasts were grown in different serum concentrations, plated at different densities, and grown for different periods of time to alter the metabolic activity of the cells. Deoxyribonucleic acid, ribonucleic acid, and protein syntheses were measured by the ability of the cells to incorporate thymidine, uridine, and leucine, respectively. With each treatment, leucine incorporation remained constant. Thymidine and uridine incorporation was higher when the cells were in high serum, at low cell densities, or grown for 2 or 3 days. The appearance of an observable CPE, which was corroborated with a protein synthesis assay, correlated closely with thymidine and uridine incorporation. A more pronounced CPE was seen when thymidine and uridine incorporation was high. In addition, it was found that the first 2 h after infection by M. pneumoniae were the critical hours in determining whether a CPE would develop. This was accomplished by altering the serum concentration of the culture medium at different times postinfection and thereby altering the metabolism of the fibroblasts. These results demonstrate the importance of the metabolic state of the host cells in studying mycoplasma infections and establish a correlation between the nucleic acid metabolism of the cells and the production of a CPE.

Effects of salt extraction on the quantitation of nuclear estrogen receptors: interference by secondary estrogen binding sites.

The effects of salt-extraction on type I and type II estrogen binding sites were examined in uterine nuclei. Injection (10 ug) of estradiol or estriol in adult ovariectomized rate induced maximum numbers (80-100%, integral of 1 pmole/uterus) of 0.4 M KCL resistant type I estrogen complexes at 1 hour. Only estradiol, which sustained these levels for long periods of time (4-24 hours) stimulated true uterine growth. Likewise, a single injection of estradiol, but not estriol, also elevated nuclear type II sites throughout the entire uterine growth period (1 - 48 hours). However extraction of these nuclei from estradiol injected rats with 0.4 M KCL increased the numbers of type II sites from integral of 1 pmole/uterus (non-extracted nuclei) to integral of 8 pmoles/uterus (salt resistant plus salt-extractable fractions). Sixty percent of these sites were resistant to salt-extraction. Continuous exposure to either estradiol or estriol by beeswax implants stimulated nuclear type II sites which were highly resistant (80%) to KCL-extraction, and additional sites were not exposed by high salt. Thus chronic treatment with both estrogens "locked in" nuclear type II sites such that they were resistant to KCL-extraction. This resistance of type II sites to salt-extraction correlated with the ability of estradiol and estriol implants to stimulate true uterine growth. The procedures presented here for nuclear preparation and assay have reduced non-specific binding considerably in the uterine system, and may eliminate the need to perform exchange assays on salt-extracted nuclei in other systems.

Isolation and phenotypic characterization of virulence-deficient mutants of Vibrio cholerae.

Mutants of Vibrio cholerae was isolated on the basis of reduced ability to induce diarrhea in orally challenged infant mice. Nitrosoguanidine-treated clones were screened for low fluid accumulation ratios in individual mice, and presumptive mutants were confirmed in additional mouse tests. Mutants were examined for alterations in phage type, motility, toxin production, proteolytic activity, neuraminidase production, amylase production, morphology, growth requirements, carbohydrate fermentations, in vitro growth patterns, and cell surface alterations. The types of mutants found included several with previously recognized virulence-associated markers (rough, nonmotile, toxin deficient, protease deficient); several types with pleiotropic alterations (cell morphology, decreased extracellular products); and several with no previously recognized virulence-deficient phenotype (purine requiring, cell surface altered, rapid death in vitro, no defect found). Dose-response kinetics showed that most mutants could provoke diarrhea if given in 100-fold greater numbers than the dose used for screening. Recovery of viable organisms from the gut late in infection showed reduction of survival and/or multiplication capacity for the mutants, with variation in the degree of reduction for the different classes.

Effects of estradiol-17 alpha on nuclear occupancy of the estrogen receptor, stimulation of nuclear type II sites and uterine growth.

Estriol and estradiol-17 alpha (E2-17 alpha) have classically been described as weak or impeded estrogens since they are incapable of stimulating true uterine growth when administered acutely by single injection. We have demonstrated [16] that estriol is capable of stimulating true uterine growth when the hormone is administered by paraffin implant. The possibility that E2-17 alpha is similar to estriol was examined. A single injection of E2-17 alpha causes a rapid accumulation of the estrogen receptor in uterine nuclei and this is correlated with the stimulation of early uterotropic responses. The nuclear receptor content declines rapidly and no stimulation of nuclear type II sites or true uterine growth is observed. E2-17 alpha does however stimulate the replenishment of cytoplasmic estrogen receptor. This receptor-response profile is typical of a short acting estrogen such as estriol. Chronic exposure (96 h) of mature-ovariectomized rats to estradiol-17 alpha (4 mg) by beeswax implant results in continual nuclear occupancy by estrogen receptors, dramatic stimulation of nuclear type II sites and true uterine growth. It is not possible to determine whether the uterotropic stimulation was due to direct effects of E2-17 alpha since this isomer was partially metabolized to E2-17 beta and both isomers were found in uterine nuclei after an implant of E2-17 alpha. We conclude that E2-17 alpha is capable of acting as an estrogen, either by its inherent estrogenicity or by its conversion to E2-17 beta, and that it may be dangerous to consider this steroid to be an ineffective or inadequate estrogen.