Role of Mites in Allergy to House Dust

One hundred and thirty-two patients known or suspected of allergy to house dust were skin-tested with pure extracts of four varieties of dust mites. The results show that both Dermatophagoides culinae and D. pteronyssinus probably played important parts in sensitizing susceptible people, as did Glycyphagus destructor and G. domesticus in some cases. In some patients these results enabled successful desensitization against the dust to be carried out, and for corticosteroid therapy to be stopped. Hence the use of mite extracts is considered to be an important advance in the diagnosis of allergy to house dust.     

House Dust Mites,how they affect asthma,eczema and other allergies

Book Review

House Dust Mites, how they affect asthma, eczema and other allergiesDes Whitrow: Elliot Right Way Books, Kingswood, Surrey (UK), 1995. Paperback, 191 pp. £3.99     

Treatment of House Dust Allergy

A controlled trial of the treatment of asthma by injections of a commercially produced extract of house dust is reported on 96 patients. The patients were allocated at random to two groups. One group received extract of house dust in a carbol saline solution, the other a carbol saline solution only. Some patients in both groups were advised on dust control in their houses.Results were available for comparison from 70 patients, 33 treated and 37 controls. Neither the treatment with house dust extract nor advice on dust control was found to give any advantage.     

Groups and Sources of Yeasts in House Dust

House dust contains bacteria, mycelial fungi, microarthropods, and yeasts. House dust samples collected in 25 apartments in Moscow and the Moscow region were found to contain yeasts belonging to the genera Candida, Cryptococcus, Debaryomyces, Rhodotorula, Sporobolomyces, and Trichosporon. The most frequently encountered microorganisms were typical epiphytic yeasts, such as Cryptococcus diffluens and Rhodotorula mucilaginosa, which are capable of long-term preservation in an inactive state. The direct source of epiphytic yeasts occurring in the house dust might be indoor plants, which were contaminated with these yeasts, albeit to a lesser degree than outdoor plants. Along with the typical epiphytic yeasts, the house dust contained the opportunistic yeast pathogens Candida catenulata, C. guillermondii, C. haemulonii, C. rugosa, and C. tropicalis, which are known as the causal agents of candidiases. We failed to reveal any correlation between the abundance of particular yeast species in the house dust, residential characteristics, and the atopic dermatitis of the inhabitants.     

Characterization of Lipopolysaccharides Present in Settled House Dust

The 3-hydroxy fatty acids (3-OHFAs) in lipopolysaccharides (LPS) play an important role in determining endotoxin activity, and childhood exposure to endotoxin has recently been associated with reduced risk of atopic diseases. To characterize the 3-OHFAs in house dust (HD), we used gas chromatography-mass spectrometry to assay 190 HD samples. Dust from beds, bedroom floors, family rooms, and kitchen floors was collected as part of a birth cohort study of childhood asthma (study 1) and a longitudinal study of home allergen and endotoxin (study 2). We also measured endotoxin activity with a Limulus assay and computed specific activity (endotoxin activity per nanomole of LPS). Longer-chain (C_16:0 and C_18:0) 3-OHFAs were predominant in HD compared with short-chain (C_10:0, C_12:0, and C_14:0) acids. Endotoxin activity was positively correlated with short-chain 3-OHFAs in both studies. In study 2, 3-OH C_16:0 was negatively correlated and 3-OH C_18:0 was not correlated with endotoxin activity, consistent with previous findings that the Limulus assay responds preferentially to LPS containing short-chain 3-OHFAs. Kitchen dust contained the highest concentrations of 3-OH C_10:0, the highest endotoxin activities, and the highest specific activities (P < 0.03). Bed dust contained the largest amounts of long-chain 3-OHFAs, the highest concentrations of LPS, and the lowest specific activities. Apartments had significantly different types of LPS (P = 0.03) compared with single-family homes in study 2. These data suggest that the Limulus assay may underestimate exposure to certain types of LPS. Because nontoxic LPS may have immune modulating effects, analysis of 3-OHFAs may be useful in epidemiologic studies.     

Membrane Nanowaves in Single and Collective Cell Migration

We report the characterization of three-dimensional membrane waves for migrating single and collective cells and describe their propagation using wide-field optical profiling technique with nanometer resolution. We reveal the existence of small and large membrane waves the amplitudes of which are in the range of ∼3–7 nm to ∼16–25 nm respectively, through the cell. For migrating single-cells, the amplitude of these waves is about 30 nm near the cell edge. Two or more different directions of propagation of the membrane nanowaves inside the same cell can be observed. After increasing the migration velocity by BMP-2 treatment, only one wave direction of propagation exists with an increase in the average amplitude (more than 80 nm near the cell edge). Furthermore for collective-cell migration, these membrane nanowaves are attenuated on the leader cells and poor transmission of these nanowaves to follower cells was observed. After BMP-2 treatment, the membrane nanowaves are transmitted from the leader cell to several rows of follower cells. Surprisingly, the vast majority of the observed membrane nanowaves is shared between the adjacent cells. These results give a new view on how single and collective-cells modulate their motility. This work has significant implications for the therapeutic use of BMPs for the regeneration of skin tissue.     

Protein Collective Motions Coupled to Ligand Migration in Myoglobin

Ligand migration processes inside myoglobin and protein dynamics coupled to the migration were theoretically investigated with molecular dynamics simulations. Based on a linear response theory, we identified protein motions coupled to the transient migration of ligand, carbon monoxide (CO), through channels. The result indicates that the coupled protein motions involve collective motions extended over the entire protein correlated with local gating motions at the channels. Protein motions, coupled to opening of a channel from the distal pocket to a neighboring xenon site, were found to share the collective motion with experimentally observed protein motions coupled to a doming motion of the heme Fe atom upon photodissociation of the ligand. Analysis based on generalized Langevin dynamics elucidated slow and diffusive features of the protein response motions. Remarkably small transmission coefficients for rates of the CO migrations through myoglobin were found, suggesting that the CO migration dynamics are characterized as motions governed by the protein dynamics involving the collective motions, rather than as thermally activated transitions across energy barriers of well-structured channels.     

Association of Cytokines in Individuals Sensitive and Insensitive to Dust Mites in a Brazilian Population

Introduction

Allergic reaction to dust mites is a relatively common condition among children, triggering cutaneous and respiratory responses that have a great impact on the health of this population. Anaphylactic hypersensitivity is characterized by an exacerbated response involving the production of regulatory cytokines responsible for stimulating the production of IgE antibodies.

Objective

To investigate an association of variants in cytokine genes (IL1A ⁻⁸⁸⁹, IL1B ^{−511, +3962}, IL1R ¹⁹⁷⁰, IL1RA ¹¹¹⁰⁰, IL4RA ⁺¹⁹⁰², IL12 ⁻¹¹⁸⁸, IFNG ⁺⁸⁷⁴, TGFB1 ^{codon 10, codon 25}, TNFA ^{−308, −238}, IL2 ^{−330, +166}, IL4 ^{−1098, −590, −33}, IL6 ^{−174, nt565}, and IL10 ^{−1082, −819, −592}) between patients sensitive to dust mites and a control group.

Methods

A total of 254 patients were grouped as atopic and non-atopic according to sensitivity as evaluated by the Prick Test and to cytokine genotyping by the polymerase chain reaction-sequence specific primers (PCR-SSP) method using the Cytokine Genotyping Kit.

Results

A comparison between individuals allergic to Dermatophagoides farinae, Dermatophagoides pteronyssinus, and Blomia tropicalis and a non-atopic control group showed significant differences between allele and genotype frequencies in the regulatory regions of cytokine genes, with important evidence for IL4 ⁻⁵⁹⁰ in T/C (10.2% vs. 43.1%, odd ratio [OR] = 0.15, p = 5.2 10⁻⁸, pc = 0.0000011, and 95% confidence interval [95%CI] = 0.07–0.32) and T/T genotypes (42.9% vs. 13.8%, OR = 4.69, p = 2.5 10⁻⁶, pc = 0.000055, and 95%CI = 2.42–9.09). Other associations were observed in the pro-inflammatory cytokines IL1A ⁻⁸⁸⁹ (T/T, C, and T) and IL2 ⁻³³⁰ (G/T and T/T) and the anti-inflammatory cytokines IL4RA ⁺¹⁹⁰² (A and G), IL4 ⁻⁵⁹⁰ (T/C, T/T, C, and T), and IL10 ⁻⁵⁹² (A/A, C/A, A, and C).

Conclusion

Our results suggest a possible association between single nucleotide polymorphisms (SNPs) in cytokine genes and hypersensitivity to dust mites.     

Silk Film Topography Directs Collective Epithelial Cell Migration

The following study provides new insight into how surface topography dictates directed collective epithelial cell sheet growth through the guidance of individual cell movement. Collective cell behavior of migrating human corneal limbal-epithelial cell sheets were studied on highly biocompatible flat and micro-patterned silk film surfaces. The silk film edge topography guided the migratory direction of individual cells making up the collective epithelial sheet, which resulted in a 75% increase in total culture elongation. This was due to a 3-fold decrease in cell sheet migration rate efficiency for movement perpendicular to the topography edge. Individual cell migration direction is preferred in the parallel approach to the edge topography where localization of cytoskeletal proteins to the topography’s edge region is reduced, which results in the directed growth of the collective epithelial sheet. Findings indicate customized biomaterial surfaces may be created to direct both the migration rate and direction of tissue epithelialization.     

Collective Epithelial and Mesenchymal Cell Migration During Gastrulation

Gastrulation, the process that puts the three major germlayers, the ectoderm, mesoderm and endoderm in their correct topological position in the developing embryo, is characterised by extensive highly organised collective cell migration of epithelial and mesenchymal cells. We discuss current knowledge and insights in the mechanisms controlling these cell behaviours during gastrulation in the chick embryo. We discuss several ideas that have been proposed to explain the observed large scale vortex movements of epithelial cells in the epiblast during formation of the primitive streak. We review current insights in the control and execution of the epithelial to mesenchymal transition (EMT) underlying the formation of the hypoblast and the ingression of the mesendoderm cells through the streak. We discuss the mechanisms by which the mesendoderm cells move, the nature and dynamics of the signals that guide these movements, as well as the interplay between signalling and movement that result in tissue patterning and morphogenesis. We argue that instructive cell-cell signaling and directed chemotactic movement responses to these signals are instrumental in the execution of all phases of gastrulation.     

Collective Cell Migration in Embryogenesis Follows the Laws of Wetting

Collective cell migration is a fundamental process during embryogenesis and its initial occurrence, called epiboly, is an excellent in vivo model to study the physical processes involved in collective cell movements that are key to understanding organ formation, cancer invasion, and wound healing. In zebrafish, epiboly starts with a cluster of cells at one pole of the spherical embryo. These cells are actively spreading in a continuous movement toward its other pole until they fully cover the yolk. Inspired by the physics of wetting, we determine the contact angle between the cells and the yolk during epiboly. By choosing a wetting approach, the relevant scale for this investigation is the tissue level, which is in contrast to other recent work. Similar to the case of a liquid drop on a surface, one observes three interfaces that carry mechanical tension. Assuming that interfacial force balance holds during the quasi-static spreading process, we employ the physics of wetting to predict the temporal change of the contact angle. Although the experimental values vary dramatically, the model allows us to rescale all measured contact-angle dynamics onto a single master curve explaining the collective cell movement. Thus, we describe the fundamental and complex developmental mechanism at the onset of embryogenesis by only three main parameters: the offset tension strength, α, that gives the strength of interfacial tension compared to other force-generating mechanisms; the tension ratio, δ, between the different interfaces; and the rate of tension variation, λ, which determines the timescale of the whole process.     

Collective Epithelial Migration Drives Kidney Repair after Acute Injury

Acute kidney injury (AKI) is a common and significant medical problem. Despite the kidney’s remarkable regenerative capacity, the mortality rate for the AKI patients is high. Thus, there remains a need to better understand the cellular mechanisms of nephron repair in order to develop new strategies that would enhance the intrinsic ability of kidney tissue to regenerate. Here, using a novel, laser ablation-based, zebrafish model of AKI, we show that collective migration of kidney epithelial cells is a primary early response to acute injury. We also show that cell proliferation is a late response of regenerating kidney epithelia that follows cell migration during kidney repair. We propose a computational model that predicts this temporal relationship and suggests that cell stretch is a mechanical link between migration and proliferation, and present experimental evidence in support of this hypothesis. Overall, this study advances our understanding of kidney repair mechanisms by highlighting a primary role for collective cell migration, laying a foundation for new approaches to treatment of AKI.     

Collective Cell Migration Drives Morphogenesis of the Kidney Nephron

Tissue organization in epithelial organs is achieved during development by the combined processes of cell differentiation and morphogenetic cell movements. In the kidney, the nephron is the functional organ unit. Each nephron is an epithelial tubule that is subdivided into discrete segments with specific transport functions. Little is known about how nephron segments are defined or how segments acquire their distinctive morphology and cell shape. Using live, in vivo cell imaging of the forming zebrafish pronephric nephron, we found that the migration of fully differentiated epithelial cells accounts for both the final position of nephron segment boundaries and the characteristic convolution of the proximal tubule. Pronephric cells maintain adherens junctions and polarized apical brush border membranes while they migrate collectively. Individual tubule cells exhibit basal membrane protrusions in the direction of movement and appear to establish transient, phosphorylated Focal Adhesion Kinase–positive adhesions to the basement membrane. Cell migration continued in the presence of camptothecin, indicating that cell division does not drive migration. Lengthening of the nephron was, however, accompanied by an increase in tubule cell number, specifically in the most distal, ret1-positive nephron segment. The initiation of cell migration coincided with the onset of fluid flow in the pronephros. Complete blockade of pronephric fluid flow prevented cell migration and proximal nephron convolution. Selective blockade of proximal, filtration-driven fluid flow shifted the position of tubule convolution distally and revealed a role for cilia-driven fluid flow in persistent migration of distal nephron cells. We conclude that nephron morphogenesis is driven by fluid flow–dependent, collective epithelial cell migration within the confines of the tubule basement membrane. Our results establish intimate links between nephron function, fluid flow, and morphogenesis.     

Asthma,Airway Symptoms and Rhinitis in Office Workers in Malaysia: Associations with House Dust Mite (HDM) Allergy,Cat Allergy and Levels of House Dust Mite Allergens in Office Dust

A prevalence study was conducted among office workers in Malaysia (N= 695). The aim of this study was to examine associations between asthma, airway symptoms, rhinitis and house dust mites (HDM) and cat allergy and HDM levels in office dust. Medical data was collected by a questionnaire. Skin prick tests were performed for HDM allergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae) and cat allergen Felis domesticus. Indoor temperature and relative air humidity (RH) were measured in the offices and vacuumed dust samples were analyzed for HDM allergens. The prevalence of D. pteronyssinus, D. farinae and cat allergy were 50.3%, 49.0% and 25.5% respectively. Totally 9.6% had doctor-diagnosed asthma, 15.5% had current wheeze and 53.0% had current rhinitis. The Der p 1 (from D. pteronyssinus) and Der f 1 (from D. farinae) allergens levels in dust were 556 ng/g and 658 ng/g respectively. Statistical analysis was conducted by multilevel logistic regression, adjusting for age, gender, current smoking, HDM or cat allergy, home dampness and recent indoor painting at home. Office workers with HDM allergy had more wheeze (p= 0.035), any airway symptoms (p= 0.032), doctor-diagnosed asthma (p= 0.005), current asthma (p= 0.007), current rhinitis (p= 0.021) and rhinoconjuctivitis (p< 0.001). Cat allergy was associated with wheeze (p= 0.021), wheeze when not having a cold (p= 0.033), any airway symptoms (p= 0.034), doctor-diagnosed asthma (p= 0.010), current asthma (p= 0.020) and nasal allergy medication (p= 0.042). Der f 1 level in dust was associated with daytime breathlessness (p= 0.033) especially among those with HDM allergy. Der f 1 levels were correlated with indoor temperature (p< 0.001) and inversely correlated with RH (p< 0.001). In conclusion, HDM and cat allergies were common and independently associated with asthma, airway symptoms and rhinitis. Der f 1 allergen can be a risk factor for daytime breathlessness.