Abnormal body iron distribution and erythropoiesis in a novel mouse model with inducible gain of iron regulatory protein (IRP)-1 function.

Disorders of iron metabolism account for some of the most common human diseases. Cellular iron homeostasis is maintained by iron regulatory proteins (IRP)-1 and 2 through their binding to cis-regulatory iron-responsive elements (IREs) in target mRNAs. Mouse models with IRP deficiency have yielded valuable insights into iron biology, but the physiological consequences of gain of IRP function in mammalian organisms have remained unexplored. Here, we report the generation of a mouse line allowing conditional expression of a constitutively active IRP1 mutant (IRP1) using Cre/Lox technology. Systemic activation of the IRP1 transgene from the Rosa26 locus yields viable animals with gain of IRE-binding activity in all the organs analyzed. IRP1 activation alters the expression of IRP target genes and is accompanied by iron loading in the same organs. Furthermore, mice display macrocytic erythropenia with decreased hematocrit and hemoglobin levels as well as impaired erythroid differentiation. Thus, inappropriately high IRP1 activity causes disturbed body iron distribution and erythropoiesis. This new mouse model further highlights the importance of appropriate IRP regulation in central organs of iron metabolism. Moreover, it opens novel avenues to study diseases associated with abnormally high IRP1 activity, such as Parkinson's disease or Friedreich's ataxia.

Sensitization to house dust mites in Reykjavik, Iceland, in the absence of domestic exposure to mites.

BACKGROUND: House dust mites are common sources of indoor allergens. In Reykjavik, Iceland, 9% of the young adult population had serum-specific IgE to Dermatophagoides pteronyssinus. Sensitization to mites is usually assumed to be due to exposure to house dust mites in the indoor environment. This investigation was carried out to measure the concentrations of house dust mite allergens and to investigate which species of mites were present in beds in Iceland. METHODS: A total of 197 randomly selected adults were visited at home using the European Community Respiratory Health Survey (ECRHS) II Indoor protocol. Dust samples were collected from mattresses for measurement of house dust mite allergen concentrations and to estimate the number and type of house dust mites. Additional samples from mattresses and floors were collected from the homes of 10 patients with positive skin prick tests (SPT) to D. pteronyssinus. House dust mite allergen concentrations were measured using ELISA and examination of mite species was carried out using microscopy. Climatic parameters were assessed using psychrometer readings in the bedrooms and outdoors. RESULTS: We found two single mite specimens, both D. pteronyssinus, in two dust samples. Mite allergen analyses indicated that two other dust samples had Der f 1 results close to the cut-off of 0.1 microg/g of dust. No samples were positive for Der p 1. In an additional collection of dust from the homes of 10 SPT-positive patients no Dermatophagoides spp. were found. CONCLUSIONS: Reykjavik citizens are exposed to extremely low amounts of house dust mite allergens in their homes. Possible alternative sources for sensitization are discussed, such as bird nests, exposure from travelling abroad, or other mites or invertebrates that cross-react with house dust mite allergens. Our findings suggest that exposures other than to house dust mites indoors are possible sources of mite allergen exposure.

House dust mites and their allergens at selected locations in the homes of house dust mite-allergic patients.

BACKGROUND: Knowledge of the occurrence of house dust mites (HDM) and their allergens in domestic locations is important when planning intervention. OBJECTIVE: The aim of this study was to describe the distribution of HDMs and their allergens before intervention in multiple locations in the homes of newly diagnosed HDM-allergic patients with a known high Der 1 concentration in their mattress dust. METHODS: Dust was collected from ten locations in the homes of eight HDM-allergic patients. Dust was analysed for allergen content with ELISAs for Der f 1, Der p 1 and Der m 1; and HDM were counted. Total allergen concentrations ( micro g Der 1/g dust) were expressed as the sum of Der f 1, Der p 1 and Der m 1. RESULTS: On mattresses the median concentration was 86 micro g Der 1/g dust (range 30-288) and 188 mites/g dust (range 12-1910). Der 1 exceeded 10 micro g/g dust in mattresses (8/8), duvets/pillows (3/8), a bedroom carpet (1/1), a living room carpet (1/6), upholstered furniture (2/8) and a curtain (1/5). Uncarpeted floors, upholstered furniture, bookshelves and walls had significantly lower Der 1 concentration than the mattresses. The relative contribution of Der p 1, Der f 1 or Der m 1 to Der 1 was related to homes, rather than to the location. Der m 1 only occurred in minute amounts. CONCLUSION: For HDM intervention, our results indicate that priority should be given to the removal of allergens from mattresses, and in addition from carpets, duvets/pillows and upholstered furniture. Dust from walls, uncarpeted floors, bookshelves and curtains appear to contribute insignificantly to the domestic HDM allergen load.

Chemical control of Penthaleus major (Acari: Prostigmata) in hayfields in Iceland.

The plant parasitic mite Penthaleus major (Dugès) occurs as a pest on perennial grasses in hayfields in Iceland, northern Norway, and southern Greenland. In these areas it appears as a summer phenomenon, contrary to more southern locations, where it appears as a pest on winter crops. Up to 500 individuals of P. major were collected per day in pitfall traps. Spring application of 44 ml/ha of permethrin and 5 ml of deltamethrin significantly reduced but did not eliminate the populations of P. major the following weeks. In addition to this immediate effect, spring application also decreased the mite populations in the fall and even the following spring. Additional effects might be obtained by earlier spring application. Despite a significant reduction in mite populations and reduction in visible plant damage, significant differences on dry matter yield were rarely registered. A side effect of application was a small but significant reduction in potassium-content of the yield, and the reduction in mite population was accompanied by a corresponding reduction in the number of spiders.

Pitfalls in evaluating mite exposure from house-dust samples.

Results from vacuum collected samples from a patient's environment may support the diagnosis of mite allergy. High estimates of mites or mite allergens do show that a patient is exposed. Low estimates are harder to interpret. Estimates may be low due to dust dynamics or to the behaviour of the mites, which, according to their biology, can be present or almost absent in the samples. A survey is given of the nature of these obstacles to proportionality between sample results and the exposure which might be experienced by a patient during a period of time. To reduce the problems of false-negative estimates of exposures from single samples, series of samples collected weeks apart may improve the significance of diagnoses.

Peak expiration flow variations may reflect house-dust-mite exposure and patient reactivity.

Peak expiration flow records from patients allergic to house-dust mites (Dermatophagoides spp.) may show a characteristic variation from week to week due to the general life cycle of these mites in dwellings. This was demonstrated from the combined records of 10 patients recorded in their own homes, covering a period of 30 consecutive weeks and comprising 973 peak flows. The levels of house-dust mites were predicted from published data for floor-dust samples from Danish dwellings. Peak flow increased or decreased in accordance with weekly changes in the concentration of mites, rather than as an immediate reaction to the current concentration of live, active mites. A dose-response relation was demonstrated. This suggests that the patients' peak flow variations might be linked to molting in mites. As such, peak flow measurements have a potential as a tool for the specific diagnosis of, monitoring of, and research in asthma caused by domestic mites.

Does guanine concentration in house-dust samples reflect house-dust mite exposure?

Using specific ELISA extracts, we analyzed samples of pure mite cultures and house dust for group I allergens from Dermatophagoides pteronyssinus, D. farinae, and D. microceras. Correspondingly, we measured the concentration of guanine and xanthine by rigorous chemical methods. The pure mite cultures were used to correlate allergen levels with guanine levels. The house-dust samples one-sidedly contained more guanine than expected. This suggests that considerable amounts of guanine originate from non-house-dust mite sources and implies that guanine quantifications are of limited clinical value.

A one-year case study of farmers with storage mite allergy.

Four farmers with a positive bronchial challenge test to either L. destructor or T. putrescentiae had bronchial histamine challenge every second month during a year. In the same year, monthly samples of house dust, grain, straw and hay were analyzed for their content of house dust mites and storage mites. The exposure to house dust mites and storage mites differed between farmers. Significant changes in histamine reactivity were found, but no association with time of year or mite counts was observed.

Mite allergy and exposure to storage mites and house dust mites in farmers.

Sensitization to house dust mites, storage mites and other common inhalation allergens was studied in 144 farmers using SPT and RAST. The study population was selected from a random sample of 808 farmers and consisted of 47 persons who had declared themselves to suffer from asthma, 63 persons who had reported respiratory symptoms, and 34 healthy persons without respiratory symptoms. The most prevalent RAST was towards storage mites and was found in 17% of farmers who suffered from asthma and was estimated to occur in 5% of the random sample of farmers. A positive RAST to house dust mites was found in 17% of farmers who reported to suffer from asthma. Sensitization to pollens, animal dander and grain species was rare. A positive RAST to moulds was not found. There was a strong association between a positive RAST to house dust mites and a positive RAST to storage mites (odds ratio 21.0). A positive RAST to storage mites was significantly associated with living in a dwelling in the past which was recalled as damp (odds ratio 4.9). A high number of house dust mites was found in nearly all dwellings (median count 148 mites/0.1 g dust) and a high number of storage mites was found in some dwellings. This study suggests that in humid and temperate regions of Europe, allergy to storage mites in farmers is not caused exclusively by occupational exposure but damp housing conditions and indoor exposure to storage mites may also be important.

Lung function and bronchial reactivity in farmers.

The purpose of this study was to evaluate the prevalence and type of lung function disorders in Danish farmers. Three samples of farmers were drawn from a group of unselected farmers who had participated in an epidemiological study. Group I (47 persons) was a sample of the 8% of all farmers who had reported that they had asthma; group II (63 persons) was a sample of the 28% of farmers who had had wheezing, shortness of breath, or cough without phlegm; and group III (34 persons) a sample of the farmers (64% of the total) who had no asthma and no respiratory symptoms. The farmers with symptoms (groups I and II) had low mean levels of FEV1 and high values for residual volume, whereas the symptomless farmers had normal lung function and no airways obstruction. The proportion of farmers with an FEV1 below the 95% confidence limit for predicted values was 43% in group I and 23% in group II; there were none in group III. Bronchial hyperreactivity to histamine occurred in 96% of asthmatic farmers, 67% of farmers with wheezing or shortness of breath, and 59% of symptomless farmers. A low level of FEV1 was associated with the number of years in pig farming and bronchial hyperreactivity in group II but not group I or III. Most of the bronchial hyperreactivity was explained in the multiple regression analysis by a low FEV1, though this was significant only for farmers in group II. Thus farmers who reported asthma, wheezing, shortness of breath, or a dry cough in general had airways obstruction with an increased residual volume, whereas symptomless farmers had normal lung function. Severe bronchial hyperreactivity was mostly explained by a diagnosis of asthma and poor lung function, though some farmers with normal lung function and no respiratory symptoms had increased bronchial reactivity.

Respiratory symptoms in Danish farmers: an epidemiological study of risk factors.

An epidemiological study was performed with a self administered questionnaire in a representative sample of 1685 Danish farmers. The purpose of the study was to assess the prevalence of self reported asthma, wheezing during work, and symptoms of chronic bronchitis and to evaluate possible risk factors for the development of these symptoms. A response rate of 73.3% was obtained. The prevalence of asthma was 7.7% and of chronic bronchitis 23.6% in responders. The prevalence of asthma and chronic bronchitis increased from 3.6% and 17.9% in 31-50 year old farmers to 11.8% and 33.0% in 51-70 year old farmers, and from 5.5% and 17.5% in dairy farmers to 10.9% and 32.0% in pig farmers. A logistic regression analysis with correction for age and smoking habits confirmed that pig farming was a risk factor for asthma (odds ratio 2.03), chronic bronchitis (odds ratio 1.53), and wheezing during work (odds ratio 3.33).

Storage mites as a cause of bronchial asthma in Denmark.

From October 1982 to July 1983, 133 consecutive patients complaining of allergic symptoms were prick-tested with three storage mites (Acarus siro, Lepidoglyphus destructor, Tyrophagus putrescentiae) and two housedust mites (Dermatophagoides pteronyssinus and Dermatophagoides farinae). A total of 60 patients (45%) had a positive prick-test for one or more of the storage mites. A mutual positive correlation was found between the prick-test results for the two house-dust mites as well as for the three storage mites. No significant correlation was found between house-dust mites and storage mites. Four cases of allergy to storage mites are presented. The diagnosis of storage mite allergy was based on the clinical history, prick-test, bronchial provocation test and the finding of storage mites in the environment of the patient. Our study suggests that allergies to storage mites could be rather frequent in the Danish population.