High breast milk IL-1ß level is associated with reduced risk of childhood eczema.

BACKGROUND: We recently demonstrated a dual effect of breastfeeding with increased risk of eczema and decreased risk of wheezing in early childhood by increasing breastfeeding length. We hypothesize that immune mediators in breast milk could explain such association either through a direct effect or as a surrogate marker of maternal immune constitution. OBJECTIVE: To investigate the possible association between cytokine and chemokine levels in breast milk and development of eczema and recurrent wheeze during early childhood. METHODS: Levels of 19 pro-inflammatory and immunoregulatory cytokines and chemokines were measured in 223 breast milk samples from mothers in the Copenhagen Prospective Study on Asthma in Childhood2000 (COPSAC) high-risk birth cohort. Eczema and recurrent wheeze at the age of 0-3 years were prospectively diagnosed by COPSAC physicians adherent to predefined validated algorithms. Association analyses were performed by Cox regression adjusting for potential confounding factors and by multivariable principal component analysis. RESULTS: Increased IL-1ß in breast milk (≥ 0.7 pg/mL) was associated with more than a halved risk of eczema before age three (aHR = 0.41; 95% CI = 0.24-0.68; P < 0.001), which remained significant after false discovery rate adjustment (P = 0.008). The principal component analysis confirmed that a mediator pattern dominated by high levels of IL-1ß, IL-17A, and CCL17 and low levels of CXCL1 and TSLP in breast milk protected against eczema (aHR = 0.82; 95% CI = 0.68-0.98; P = 0.03). No associations were observed for recurrent wheeze. CONCLUSIONS AND CLINICAL RELEVANCE: Elevated breast milk IL-1ß level was associated with decreased risk of early childhood eczema suggesting either a direct protective effect of IL-1ß or IL-1b acting as a proxy for a healthy maternal immune system protecting high-risk offspring from eczema.

Enabling sense-making for patients receiving outpatient palliative treatment: A participatory action research driven model for person-centered communication.

OBJECTIVES: In clinical palliative cancer care, the diversity of patient concerns over time makes information provision a critical issue, the demands of information-seeking patients presenting a challenge to both the communicative and organizational skills of the health provider. This study puts forward a practice model for communication between patients, their family members, and professional health providers during ongoing palliative chemotherapy; a model which supports the providers in enabling person-centered communication. METHOD: A constant comparative analysis adapted to participatory action research was applied. The model was developed step-wise in three interrelated cycles, with results from previous studies from palliative cancer care processed in relation to professional health providers' experience-based clinical knowledge. In doing this, focus group discussions were carried out with providers and patients to develop and revise the model. RESULTS: The Enabling Sense Making model for person-centered communication gave rise to three domains (which are also the major communicative actors in palliative care): the patient, the family, and the provider. These actors were placed in the context of a communicative arena. The three respective domains were built up in different layers discriminating between significant aspects of person-centered communication, from the manifest that is most usually explicated in dialogues, to the latent that tends to be implicitly mediated. SIGNIFICANCE OF RESULTS: The model intends to facilitate timely reorientation of care from curative treatment or rehabilitation to palliation, as well as the introduction of appropriate palliative interventions over time during palliative phases. In this way the model is to be regarded a frame for directing the awareness of the professionals, which focuses on how to communicate and how to consider the patient's way of reasoning. The model could be used as a complement to other strategic initiatives for the advancement of palliative care communication. It needs to be further evaluated in regard to practice evidence.

Sulfur dioxide contributions to the atmosphere by volcanoes.

The first extensive measurements by remote-sensing correlation spectrometry of the sulfur dioxide emitted by volcanic plumes indicate that on the order of 10(3) metric tons of sulfur dioxide gas enter the atmosphere daily from Central American volcanoes. Extrapolation gives a minimum estimate of the annual amount of sulfur dioxide emitted from the world's volcanoes of about 10(7) metric tons.

The behavior of subcultivated stratified squamous epithelial cells on reconstituted extracellular matrices: initial interactions.

Stratified squamous epithelial cells derived from the ventral surface of the rat tongue interact with matrices composed of hydrated dermal collagens (types I and III) and with a bovine basement membrane in distinctly different ways. When compared with the behavior of the cells on the basement membrane, the attachment and subsequent migration of the cells on the collagens were inefficient and slow. The resultant epithelial colonies did, however, stratify and differentiate more rapidly than those formed on the membrane. The fibrillar meshwork of the type III collagen gel provided better initial support for the cells than did the gel of type I collagen in which the fibrils were arranged as coarse aggregates. The physical characteristics of the type III gel also allowed the cells to condense the surface resulting in even better epithelial support. The basement membrane encouraged rapid epithelial coverage of large areas by promoting cell attachment and migration. This important property indicates that epithelial discontinuities can be rapidly repaired, providing the cells can migrate along a preexistent basement membrane. The use of such defined extracellular matrices in culture can provide important insight into the function and structural organization of subepithelial connective tissues and basement membranes.

Growth of stratified squamous epithelium on reconstituted extracellular matrices: long-term culture.

Oral keratinocytes grown at an air-liquid interface on stabilized matrices of collagen or a basement membrane exhibit a pattern of tissue organization more similar to the parent tissue than the same cells cultured conventionally. An orderly sequence of cell migration and differentiation is maintained, and the full complement of terminally differentiated cells is retained on the surface of the culture for up to 65 days following subculture. The pattern of histodifferentiation of cultured stratified squamous epithelium differs according to the matrix upon which it is grown. Pliant, fine meshed gels of type III collagen are corrugated by the cultured keratinocytes with adjustments occurring in the various suprabasal cell strata that result in the retention of a flat stratum corneum. Such pliant gels can be stabilized by pouring a supporting underlayer of coarse type I guinea pig collagen. Keratinocytes grown directly on the irregular surface of guinea pig type I collagen migrate into spaces between collagen fibrillar bundles and aberrantly keratinize 20-30 days following subculture. Keratinocytes grown on a basement membrane do not aberrantly keratinize, suggesting that contact with a basement membrane may suppress signals for keratinocyte differentiation. Keratinocytes also form hemidesmosomes opposite a basement membrane but not opposite collagen fibrils. The keratin pattern of oral keratinocytes cultured in different configurations does not change; a finding that indicates that a greater degree of tissue organization does not automatically result in the synthesis of keratins more characteristic of upper cell strata or cornified cells in the native tissue.

The growth and structure of human oral keratinocytes in culture.

Human keratinocytes derived from explants of cheek (buccal) mucosa grow vigorously in culture and can be subcultivated twice. The structure of the oral keratinocytes in vitro is the same in primary cultures and subcultures. The cells stratify, are characterized by well-developed tonofibrillar-desmosomal complexes, and rarely exhibit signs of terminal differentiation. Unique features of the culture system that favor keratinocyte growth are: incubation at 34 degrees C, inclusion of 0.5% dimethyl sulfoxide in the culture medium, and initiating subcultures as 5.0 mm colonies containing 100,000/20 microliter of medium. One primary culture can yield 6 first-passage subcultures, which subsequently achieve confluence in 10-12 days. Such cultures are a useful source of human keratinocytes that stratify but generally do not undergo terminal differentiation.

Antagonistic effect of selenite on tumor promoter induced cell proliferation in cultures of rat tongue epithelium.

In cultures of rat tongue epithelial cells, cell proliferation following incubation with different doses of the potent tumor promoter TPA has been studied by using a stathmokinetic method counting colchicine arrested metaphases. It was demonstrated that 24 h incubation with concentrations higher than 5 ng TPA/mL medium caused inhibition, whereas below 5 ng TPA/mL medium caused stimulation of the mitotic activity reaching a maximum around 30 h from the start of the incubation period. Based on the evidence of the anticarcinogenic effect of selenium in several animal models, experiments have been performed elucidating the influence of an atoxic dose (1/1.000.000M) of selenite on the observed TPA-induced cell proliferation. Our results indicate that addition to the culture medium of an atoxic dose of selenite, not affecting the mitotic activity of control cultures, inhibits the TPA-induced stimulation of cell proliferation.

Construction of a multidimensional scale of job satisfaction.

A comprehensive, multidimensional scale measuring job satisfaction was constructed for use in a major project concerned with personnel recruitment and retention of health professionals. 11 dimensions relating to opinions of immediate supervisors, physical working conditions, satisfaction with coworkers and with pay, aspects related to promotion and work motivation, are identified. These dimensions are shown to distinguish among health professionals on sex and between locations and different occupations. The scale also has high internal validity, producing a multiple R of .78 with over-all job satisfaction.

Ambient ground level monitoring: a sensible control system for the industry.

Sulfur emission rules are being changed. This action and a proposed EPA Supplementary Control strategy that would allow industrial facilities to continue their operations based on emission measurements and weather conditions is a logical step. Nevertheless, other EPA requirements and limitations are not acceptable to the electric power generating industry. Effective sulfur removal processes and equipment are yet beyond the "state of the art" and thus are not cost effective capital investments while the technology is in development. Field proven ambient monitoring networks are available now to implement fuel switching which is the preferred method of the power industry. This permits remaining within ambient limits, thus fulfilling the basic requirements of the primary SQX stand"... to protect the public health.".

The permeability of a keratinizing squamous epithelium in culture.

Horseradish peroxidase or lanthanum was applied to the surface of keratinized oral epithelium growing in tissue culture and the extent of penetration of these substances examined with the electron microscope. Both tracer substances penetrated between the superficial keratinized squames of the tissue, the lanthanum reaching the basal cell layer and the peroxidase diffusing to within 3--8 cells of the basal layer. The permeability of the keratinized layer in this epithelium is in contrast to the situation in vivo where an intercellular barrier is found in the superficial layer. This difference might be related to the absence of membrane-coating granules from the tissue maintained in culture.

Behavior of in vitro grown normal human mucosal epithelial cells and tumorigenic rat cells inoculated into nude mice.

The present study describes the behavior of in vitro grown normal human oral mucosal epithelial cells and that of a tumorigenic epithelial cell line following subcutaneous inoculation into nude mice. A successful recovery of viable human epithelial cell inocula was seen in 25-90% of mice and there was no improvement in recovery rates after addition of fibroblasts. These inocula resulted in cyst formation lined by a 2-6 cell layer unkeratinized squamous epithelium without rete ridges. There was no increase in recovery rate or size of cysts when coinoculated with fibroblasts. The tumorigenic cell inocula were successfully recovered in all cases. Tumors established from these inocula had a low grade of differentiation and were without signs of metastasis. Inocula of tumorigenic cells showed an increased size after addition of fibroblasts to the inocula. The model may be useful in studies of interactions between inoculations of heterologous normal and pathologic cells as well as in studies of differentiation of carcinogen-treated epithelial cells.

A system for the study of epidermal G1-chalone in cell culture. The rat tongue epithelial cell line RTE2.

A pig-skin preparation enriched in epidermal G1-chalone when administered to cells of the rat tongue epithelial line RTE2 at concentrations of 3-300 micrograms/ml (dry mass) caused a 60% reduction in cell number. Three other cell lines showed essentially no growth inhibition during chalone treatment. The kinetics of chalone inhibition were similar to those observed in mouse epidermis in vivo. Five hours after the addition of chalone preparation in fresh medium a decrease in the rate of DNA synthesis was observed. Maximum inhibition at 12 h was followed by a subsequent increase in DNA synthesis, reaching control values again after 30 h. The inhibitory effect was dose-dependent up to 3 micrograms/ml. At higher concentrations the degree of inhibition remained constant at about 50% of the control up to 300 micrograms/ml. Removal of added chalone by changing the medium at the time of maximum inhibition gave rise to a complete recovery within 9 h. These results indicate a cell-line specific, non-toxic and reversible inhibitory effect of the chalone preparation which resembles that observed in the living animal. The RTE2 cell line may thus be considered to provide a highly sensitive experimental system suitable for more detailed studies on the mechanism of action of epidermal G1-chalone.

Metabolism of benzo[a]pyrene by cultured rat and human buccal mucosa cells.

Primary cultures of epithelial and fibroblast cells derived from human oral mucosa were studied for the ability to activate a tobacco smoke carcinogen, benzo[a]pyrene (BP). The cells were exposed to benzo[a]pyrene for 18 h. The cell-free medium was extracted with ethylacetate/acetone, and high-pressure liquid chromatography analysis of this fraction revealed that BP tetrols and diols were the major metabolites formed by both epithelial and fibroblast cells. However, the epithelial cells had a much higher rate of biotransformation of BP as measured by binding to cellular DNA. The mean binding level to human buccal mucosal DNA was among the highest observed in stratified human epithelia. The major BP-DNA adduct was formed by the reaction of the 'bay-region' BP diolepoxide with the exocyclic 2-amino group in guanine. In contrast to human cells, BP phenols and BP 9,10-diol were the major metabolites produced by primary epithelial and fibroblast cells derived from rat buccal mucosa. The DNA binding levels of BP in the two rat cell types were identical, and the binding level was several-fold lower than in the human epithelial cells. When an established rat tongue epithelial cell line (RTE 2) was treated with polycyclic aromatic hydrocarbons--BP and 7,12-dimethylbenz[a]-anthracene--a slight toxic effect was observed. Our results indicate that primary cultures of oral mucosa are able to metabolize BP into its ultimate carcinogenic form at a rate similar to or higher than other potential target tissues for BP-induced carcinogenesis.

Herpes simplex virus-induced changes of the keratin type intermediate filament in rat epithelial cells.

Herpes simplex virus type 1 (HSV-1) infection of human fibroblast cells grown in culture induces reorganization of the cytoskeleton fibrillar structures. Normal transport and insertion of HSV glycoproteins into the plasma membrane of the cells depend on the integrity of the microtubules. The natural host cells for HSV are epithelial cells, and an epithelial cell line established from rat palate was used in the present study. The effect of virus on the structure of the intermediate filaments and especially on the keratin proteins was studied. Two-dimensional gel electrophoresis of total cell extracts identified in uninfected cells two major acidic keratin proteins with apparent molecular weights of 44,000 (44K) and 48K (pI 5.45 to 5.30, 5.50 to 5.35). A new keratin protein of 46K (pI 5.40 to 5.25) appeared in infected cells between 8 h and 12 h post-infection. Pulse-chase experiments identified the 46K protein as a processed form of the 48K keratin component, which was also cleaved in uninfected cells grown in the presence of cycloheximide. Partial proteolysis of the 46K and 48K keratins with Staphylococcus aureus V8 protease showed that the 48K and the 46K proteins differed in only one oligopeptide. The significance of the changed keratin composition of HSV-infected cells is discussed.

Chemically unrelated tumor promoters induce identical morphological changes in cultured rat oral epithelium.

By use of phase contrast microscopy, transmission and scanning electron microscopy the cytomorphological effects of different known tumor promoters (TPA, teleocidin, mezerein and anthralin) were studied and compared to the cytomorphological effects of a variety of non- or weak promoting irritants (ethylphenylpropiolate (EPP), phorbol, acetone, ethanol and dimethyl sulfoxide (DMSO]. The studies were conducted in cultures of stratifying rat tongue epithelial cells. It was demonstrated that the tumor promoters induce characteristic cytomorphological alterations, the most striking changes being elongation of the cells and formation of long cytoplasmic extensions together with induction of so-called "dark cells". The non-promoting irritants exerted well-known cytotoxic reactions like cell rounding and cell sloughing. It is suggested that the characteristic tumor promotor induced cytomorphological effects partly reflects a block of the intercellular communication and thus should be paid more attention as an important characteristic event among the pleiotropic effects exerted by tumor promoters.

Effect of folic acid on human oral epithelium in vitro.

The cytomorphological effects of folic acid were studied using in vitro established human oral epithelium. It was demonstrated that a concentration twice that used clinically (200 micrograms/ml) did not induce marked cytotoxic reaction in the cultured cells. The most pronounced changes were observed in cultures exposed to 200 micrograms/ml folic acid both in primary culture and subculture. The cultures displayed areas of degenerating cells showing oedema and increased translucency of the cytoplasm, flattened cells with distinct tonofilaments and atypical mitotic figures. Identical changes were found in cultures exposed to 50 and 100 micrograms/ml folic acid but to a lesser extent than in 200 micrograms/ml. These changes indicated that folic acid increased the number of cells undergoing terminal differentiation. From this study we suggested that folic acid when applied topically may play a role in local stimulation of epithelial cell differentiation leading to enhanced healing of oral ulcers.

Effect of subharmonics on two-wave gain in Bi(12)SiO(20) under alternating electric fields.

It is demonstrated that the emergence of subharmonics during two-wave mixing in a Bi(12)SiO(20) photorefractive crystal under applied alternating electric fields will markedly reduce two-wave gain. The repetition frequency at which the observed drop in two-wave gain appears is correlated with threshold conditions for the subharmonic instability for a wide range of experimental parameters.

Convolution-kernel-based optimal trade-off filters for optical pattern recognition.

An architecture for the implementation of optical pattern recognition is proposed that makes use of convolution-kernel-based optimal trade-off filters to allow for an increased speed of operation and filter storage capability. The derivation of these new convolution-kernel-based optimal trade-off filters is presented, and their noise robustness and discrimination capabilities are discussed.