Endoscopic ultrahigh resolution optical coherence tomography (UHR OCT) achieves an axial image resolution of approximately 5 microm, which is 2 - 3 times finer than standard endoscopic OCT imaging. ...This study investigated the capability of endoscopic UHR OCT for imaging patients with Barrett's esophagus.
Fivty volunteers previously diagnosed with Barrett's esophagus underwent UHR OCT. Imaging was performed at 1.3 microm wavelengths with approximately 5 microm axial and approximately 15 microm transverse resolutions using a 1.8 mm/diameter linear-scanning catheter introduced through the accessory channel of a standard endoscope. OCT images were compared with endoscopic diagnosis and pinch biopsy histological appearances.
UHR OCT images of normal esophagus, Barrett's esophagus, high grade dysplasia and esophageal adenocarcinoma were evaluated. UHR OCT images of the normal esophagus exhibited characteristic layered architecture with uniform epithelium, while images of Barrett's esophagus corresponded to crypt-like glandular structures. High grade dysplasia and esophageal adenocarcinoma images exhibited more heterogeneous structures corresponding to irregular, heterogeneous tissue morphology from distorted and cribriform or villiform glandular architecture. Fine features can be discerned more clearly with endoscopic UHR OCT.
This study evaluated new endoscopic OCT technology and demonstrated the feasibility of carrying out UHR OCT imaging in conjunction with standard endoscopy for in vivo real-time imaging of Barrett's esophagus, dysplasia, and esophageal adenocarcinoma. A survey of normal and abnormal upper gastrointestinal tissues was performed using a research prototype OCT system with the highest axial resolution to date, and can serve as a baseline for future investigation.
A distally actuated, rotational-scanning micromotor endoscope catheter probe is demonstrated for ultrahigh-resolution in vivo endoscopic optical coherence tomography (OCT) imaging. The probe permits ...focus adjustment for visualization of tissue morphology at varying depths with improved transverse resolution compared with standard OCT imaging probes. The distal actuation avoids nonuniform scanning motion artifacts that are present with other probe designs and can permit a wider range of imaging speeds. Ultrahigh-resolution endoscopic imaging is demonstrated in a rabbit with <4-microm axial resolution by use of a femtosecond Cr:forsterite laser light source. The micromotor endoscope catheter probe promises to improve OCT imaging performance in future endoscopic imaging applications.
A method for the fabrication of thick films of porous anodic alumina on rigid substrates is described. The anodic alumina film was generated by the anodization of an aluminum film evaporated on the ...substrate. The morphology of the barrier layer between the porous film and the substrate was different from that of anodic films grown on aluminum substrates. The removal of the barrier layer and the electrochemical growth of nanowires within the ordered pores were accomplished without the need to remove the anodic film from the substrate. We fabricated porous anodic alumina samples over large areas (up to 70 cm2), and deposited in them nanowire arrays of various materials. Long nanowires were obtained with lengths of at least 9 μm and aspect ratios as high as 300. Due to their mechanical robustness and the built‐in contact between the conducting substrate and the nanowires, the structures were useful for electrical transport measurements on the arrays. The method was also demonstrated on patterned and non‐planar substrates, further expanding the range of applications of these porous alumina and nanowire assemblies.
Large‐area porous anodic alumina films lacking a barrier layer, and nanowire arrays of high aspect ratio nanowires (∼102) in direct contact with a conductive film, have been formed on rigid substrates. The effect of different substrates on the morphology of the film and the barrier layer was examined, and the ease of manipulation of the structures was demonstrated by patterning the films and by nanowire transport measurements.
In early life, the innate immune system can recognize both viable and nonviable parts of microorganisms. Immune activation may direct the immune response, thus conferring tolerance to allergens such ...as animal dander or tree and grass pollen.
Parents of children who were 6 to 13 years of age and were living in rural areas of Germany, Austria, or Switzerland where there were both farming and nonfarming households completed a standardized questionnaire on asthma and hay fever. Blood samples were obtained from the children and tested for atopic sensitization; peripheral-blood leukocytes were also harvested from the samples for testing. The levels of endotoxin in the bedding used by these children were examined in relation to clinical findings and to the cytokine-production profiles of peripheral-blood leukocytes that had been stimulated with lipopolysaccharide and staphylococcal enterotoxin B. Complete data were available for 812 children.
Endotoxin levels in samples of dust from the child's mattress were inversely related to the occurrence of hay fever, atopic asthma, and atopic sensitization. Nonatopic wheeze was not significantly associated with the endotoxin level. Cytokine production by leukocytes (production of tumor necrosis factor alpha, interferon-gamma, interleukin-10, and interleukin-12) was inversely related to the endotoxin level in the bedding, indicating a marked down-regulation of immune responses in exposed children.
A subject's environmental exposure to endotoxin may have a crucial role in the development of tolerance to ubiquitous allergens found in natural environments.
Recent studies in transgenic mice have revealed that expression of a dominant negative form of the transcription factor GATA-3 in T cells can prevent T helper cell type 2 (Th2)-mediated allergic ...airway inflammation in mice. However, it remains unclear whether GATA-3 plays a role in the effector phase of allergic airway inflammation and whether antagonizing the expression and/or function of GATA-3 can be used for the therapy of allergic airway inflammation and hyperresponsiveness. Here, we analyzed the effects of locally antagonizing GATA-3 function in a murine model of asthma. We could suppress GATA-3 expression in interleukin (IL)-4-producing T cells in vitro and in vivo by an antisense phosphorothioate oligonucleotide overlapping the translation start site of GATA-3, whereas nonsense control oligonucleotides were virtually inactive. In a murine model of asthma associated with allergic pulmonary inflammation and hyperresponsiveness in ovalbumin (OVA)-sensitized mice, local intranasal administration of fluorescein isothiocyanate-labeled GATA-3 antisense oligonucleotides led to DNA uptake in lung cells associated with a reduction of intracellular GATA-3 expression. Such intrapulmonary blockade of GATA-3 expression caused an abrogation of signs of lung inflammation including infiltration of eosinophils and Th2 cytokine production. Furthermore, treatment with antisense but not nonsense oligonucleotides induced a significant reduction of airway hyperresponsiveness in OVA-sensitized mice to levels comparable to saline-treated control mice, as assessed by both enhanced pause (PenH) responses and pulmonary resistance determined by body plethysmography. These data indicate a critical role for GATA-3 in the effector phase of a murine asthma model and suggest that local delivery of GATA-3 antisense oligonucleotides may be a novel approach for the treatment of airway hyperresponsiveness such as in asthma. This approach has the potential advantage of suppressing the expression of various proinflammatory Th2 cytokines simultaneously rather than suppressing the activity of a single cytokine.
The introduction of routine vaccination with heptavalent conjugated pneumococcal vaccine has changed the overall incidence of bacteremia in children 3 months-3 years old.
To describe the changing ...incidence and etiology of bacteremia in previously healthy toddlers presenting to outpatient clinical settings.
Retrospective case series of all blood cultures obtained between September 1998 and August 2003 in Kaiser Permanente Northern California outpatient clinics and emergency departments from previously healthy children 3 months-3 years old.
Implementation of routine vaccination with the conjugated pneumococcal vaccine resulted in an 84% reduction of Streptococcus pneumoniae bacteremia (1.3-0.2%) and a 67% reduction in overall bacteremia (1.6-0.7%) in the study population. The rate of blood culture isolation of contaminating organisms remained unchanged at 1.8%; therefore, by the end of the study, >70% of organisms identified in blood cultures were contaminants. During the 5 study years, total blood cultures drawn decreased by 35% in outpatient pediatric clinics but remained unchanged in emergency departments. By 2003, one-third of all pathogenic organisms isolated from blood cultures were Escherichia coli, one-third were non-vaccine serotype S. pneumoniae, the majority of the remaining one-third were Staphylococcus aureus, Salmonella spp., Neisseria meningitidis and Streptococcus pyogenes. In our population of children routinely immunized with the conjugated pneumococcal vaccine, a white blood cell count >15,000 by itself is a poor predictor of bacteremia in the febrile toddler (sensitivity, 74.0%; specificity, 54.5%; positive predictive value, 1.5%; negative predictive value, 99.5%).
In the United States, routine vaccinations with Haemophilus influenzae type b and S. pneumoniae vaccines have made bacteremia in the previously healthy toddler a rare event. As the incidence of pneumococcal bacteremia has decreased, E. coli, Salmonella spp. and Staphylococcus aureus have increased in relative importance. The use of the white blood cell count alone to guide the empiric use of antibiotics is not indicated. New guidelines are needed to approach the previously healthy febrile toddler in the outpatient setting.
This study investigated the potential of salivary bacterial and protein markers for evaluating the disease status in healthy individuals or patients with gingivitis or caries. Saliva samples from ...caries- and gingivitis-free individuals (
= 18), patients with gingivitis (
= 17), or patients with deep caries lesions (
= 38) were collected and analyzed for 44 candidate biomarkers (cytokines, chemokines, growth factors, matrix metalloproteinases, a metallopeptidase inhibitor, proteolytic enzymes, and selected oral bacteria). The resulting data were subjected to principal component analysis and used as a training set for random forest (RF) modeling. This computational analysis revealed four biomarkers (IL-4, IL-13, IL-2-RA, and eotaxin/CCL11) to be of high importance for the correct depiction of caries in 37 of 38 patients. The RF model was then used to classify 10 subjects (five caries-/gingivitis-free and five with caries), who were followed over a period of six months. The results were compared to the clinical assessments of dental specialists, revealing a high correlation between the RF prediction and the clinical classification. Due to the superior sensitivity of the RF model, there was a divergence in the prediction of two caries and four caries-/gingivitis-free subjects. These findings suggest IL-4, IL-13, IL-2-RA, and eotaxin/CCL11 as potential salivary biomarkers for identifying noninvasive caries. Furthermore, we suggest a potential association between JAK/STAT signaling and dental caries onset and progression.
Oral health is maintained by a healthy microbiome, which can be monitored by state-of-the art diagnostics. Therefore, this study evaluated the presence and quantity of ten oral disease-associated ...taxa (P. gingivalis, T. forsythia, T. denticola, F. nucleatum, C. rectus, P. intermedia, A. actinomycetemcomitans, S. mutans, S. sobrinus, oral associated Lactobacilli) in saliva and their clinical status association in 214 individuals. Upon clinical examination, study subjects were grouped into healthy, caries and periodontitis and their saliva was collected. A highly specific point-of-care compatible dual color qPCR assay was developed and used to study the above-mentioned bacteria of interest in the collected saliva. Assay performance was compared to a commercially available microbial reference test. Eight out of ten taxa that were investigated during this study were strong discriminators between the periodontitis and healthy groups: C. rectus, T. forsythia, P. gingivalis, S. mutans, F. nucleatum, T. denticola, P. intermedia and oral Lactobacilli (p < 0.05). Significant differentiation between the periodontitis and caries group microbiome was only shown for S. mutans (p < 0.05). A clear distinction between oral health and disease was enabled by the analysis of quantitative qPCR data of target taxa levels in saliva.
Children of farmers are at decreased risk of developing allergies. Results of epidemiological studies suggest increased exposure to microbial compounds might be responsible for this reduced risk. ...Alterations in adaptive immune response are thought to be the underlying mechanism. We measured expression of receptors for microbial compounds known to trigger the innate immune response. We showed that blood cells from farmers' children express significantly higher amounts of CD14 (0·96 vs 0·43, p=0·0013), and Toll-like receptor 2 (0·11 vs 0·04, p<0·0001) than those from nonfarmers' children. We propose that the innate immune system responds to the microbial burden in the environment and modulates the development of allergic disease.
The cytokine IL-6 acts via a specific receptor complex that consists of the membrane-bound IL-6 receptor (mIL-6R) or the soluble IL-6 receptor (sIL-6R) and glycoprotein 130 (gp130). In this study, we ...investigated the role of IL-6R components in asthma. We observed increased levels of sIL-6R in the airways of patients with allergic asthma as compared to those in controls. In addition, local blockade of the sIL-6R in a murine model of late-phase asthma after OVA sensitization by gp130-fraction constant led to suppression of Th2 cells in the lung. By contrast, blockade of mIL-6R induced local expansion of Foxp3-positive CD4+CD25+ Tregs with increased immunosuppressive capacities. CD4+CD25+ but not CD4+CD25- lung T cells selectively expressed the IL-6R alpha chain and showed IL-6-dependent STAT-3 phosphorylation. Finally, in an in vivo transfer model of asthma in immunodeficient Rag1 mice, CD4+CD25+ T cells isolated from anti-IL-6R antibody-treated mice exhibited marked immunosuppressive and antiinflammatory functions. IL-6 signaling therefore controls the balance between effector cells and Tregs in the lung by means of different receptor components. Furthermore, inhibition of IL-6 signaling emerges as a novel molecular approach for the treatment of allergic asthma.
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