Confocal scanning of genetic microarrays.
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Biomedical subjects
Publications and source records attributed to A E Dixon.
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BACKGROUND: Lung injury occurs frequently after allogeneic bone marrow transplantation in association with graft-versus-host disease, an immune response that involves both cellular and cytokine components. In a murine model, we recently showed that cloned alloreactive T helper (Th)1 cells can cause lung injury associated with increased production of tumor necrosis factor (TNF)-alpha by alveolar macrophages (J Immunol 1998; 161: 1913). METHODS: To evaluate the role of TNF-alpha in this model, we injected in vitro-activated Th1 cells into the following: (1) recipients deficient in receptors for TNF; (2) C57BL/6 control mice; (3) C57BL/6 mice, pretreated with soluble TNFRIIFc (a dimorphic high-affinity TNF antagonist); (4) mice expressing TNFRIIFc transgene under control of the surfactant apoprotein C promoter (SPCTNFRIIFc); and (5) wild-type littermate controls (C57BL/6) (n=3-6 mice/group). RESULTS: At 1 and 3 days after i.v. Th1 cell transfer, recipients were killed for analysis of lung histology, bronchoalveolar lavage (BAL) protein, and BAL cell counts. Control mice (wild type) at day 1 after injection had a mild to moderate mononuclear perivasculitis and increased interstitial cellularity. At day 3, lesions were more severe and perivasculitis also involved larger veins. TNFR-deficient mice had normal lung or minimal lung inflammation at day 1. At day 3, perivasculitis of medium-sized vessels was present, but there was no apparent involvement of larger veins. Results in mice treated with soluble TNFRIIFc and transgenic mice (SPCsTNFRIIFc) were similar to controls. BAL protein and BAL cell counts did not differ between any of the experimental groups. CONCLUSIONS: We conclude that lung inflammation induced by Th1 cells may be only delayed when TNF-alpha action is blocked. The persistence of abnormalities indicates that other proinflammatory pathways are involved in injury caused by these cells.
T helper type 1 (Th1) cells are important effectors in a number of immune-mediated lung diseases. We recently described a murine model of lung injury induced by adoptive transfer of cloned alloreactive Th1 cells. To investigate mechanisms that result in injury to the lung, we studied the in vivo distribution of (51)Cr-labeled Th1 cells. One hour after intravenous administration, >85% of injected radioactivity was left in the lung, and at 24 h, 40% of radioactivity was left in the lung. Adherence of Th1 cells in the lung was significantly inhibited by neutralizing antibody to lymphocyte function-associated antigen-1. Th1 cell adherence also was decreased in lungs of mice deficient in intercellular adhesion molecule-1 (ICAM-1). Th1 cell transfer further induced expression of ICAM-1 and vascular cell adhesion molecule-1 in the lung. Vascular cell adhesion molecule-1-immunoreactive protein was markedly induced in lung endothelium by alloreactive Th1 cells. These findings indicate that Th1 cells localize in normal lung by a mechanism involving lymphocyte function-associated antigen-1 and ICAM-1. Alloreactive cells further induce endothelial adhesion molecules that may facilitate recruitment of inflammatory cells to the lung and amplify Th1 cell-induced lung injury.
Proinflammatory responses generated by T helper type 1 (Th1) cells may contribute significantly to immune-mediated lung injury. We describe a murine model of Th1 cell-induced lung injury in which adoptive transfer of alloreactive Th1 cells produces pulmonary inflammation characterized by mononuclear cell vasculitis, alveolitis, and interstitial pneumonitis. To investigate the link between activation of Th1 cells in the lung and inflammatory cell recruitment, we characterized cytokine and chemokine mRNA expression in Th1 cells activated in vitro and in lung tissue after adoptive transfer of Th1 cells. Activated Th1 cells per se express mRNA for interferon (IFN)-gamma and several members of the tumor necrosis factor family as well as the C-C chemokine receptor-5 ligands regulated on activation normal T cells expressed and secreted and macrophage inflammatory protein-1alpha and -1beta. Additional chemokine genes were induced in the lung after Th1 cell administration, most notably IFN-gamma-inducible protein (IP-10) and monokine induced by IFN-gamma (MIG). Remarkable increases in IP-10- and MIG-immunoreactive proteins were present in inflammatory foci lung and identified in macrophages, endothelium, bronchial epithelium, and alveolar structures. The findings suggest that IFN-gamma-inducible chemokines are an important mechanism for amplifying inflammation initiated by Th1 cells in the lung.
A highly sensitive confocal scanning-beam system for time-resolved imaging of fingerprints is described. Time-resolved imaging is a relatively new forensic procedure for the detection and imaging of latent fingerprints on fluorescent substrates such as paper, cardboard, and fluorescent paint. Ordinary fluorescent imaging of latent fingerprints on these surfaces results in poor contrast. Instead, the specimens are treated with a phosphorescent dye that preferentially adheres to the fingerprint which allows time-resolved discrimination between the fingerprint phosphorescence and the background fluorescence. Time resolved images are obtained by synchronizing the digital sampling of the specimen luminescence with the on-off cycle of the chopped illumination beam. The merit of this technique is illustrated with high contrast images of fingerprints obtained from the fluorescent painted surface of a Coke can.
OBJECTIVE: This study examined whether married individuals have comparable body image disturbance to nonmarried individuals and whether the quality of a marital relationship is significantly related to body image disturbance in a sample of dieters. METHOD: Measures of marital status, marital satisfaction, and body dissatisfaction were administered to a sample of 16,377 subjects who had tried to lose weight at least once within the previous 3 years. RESULTS: Marital status was not associated with increased body dissatisfaction. Marital satisfaction was significantly related to body dissatisfaction when controlling for age, body mass index, self-esteem, and gender. DISCUSSION: Body dissatisfaction occurs at comparable levels among married and single individuals and the study of marital functioning among eating-disordered individuals represents a large gap in the literature.
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A scanning beam laser macroscope has been developed which scans an area of 7.5 x 7.5 cm in 5 s. This new imaging system is examined as a potential tool for scanning electrophoretic gels. A specially-designed telecentric, f* theta laser scan lens is used in the instrument to achieve a linear scan and a flat focal plane. The laser scan lens focuses the incoming beam from a laser to a 10 microns spot inside the gel. A raster scan is performed across the gel and the signal is detected with a photomultiplier, forming a 512 x 512 digital image stored as a computer file. Silver-stained protein polyacrylamide gels have been imaged in transmission and double-transmission, while DNA agarose gels (stained with ethidium bromide) have been imaged in fluorescence with better than 25 pg sensitivity. The macroscope has the advantage that it is not tied to the electrophoresis system as are end-of-line scanners, and the scan is rapid, so that several gels can be scanned in a very short time.
BACKGROUND AND DESIGN: The ability of superficial dermabrasion to improve clinical features of photoaged skin is well known, but the specific biological mechanisms involved are poorly understood. The so-called repair zone, as visualized by routine histologic examination, has been attributed to new collagen formation within the papillary dermis and may be responsible for clinical improvement following dermabrasion. We investigated molecular and histologic events occurring in dermabraded skin and correlated them with clinical improvement. Ten photoaged patients (mean age, 59 years) underwent facial dermabrasion to the level of the papillary dermis. Clinical severity of photoaging was graded in a blinded manner at baseline and 12 weeks after dermabrasion. Biopsy specimens obtained at baseline and 3 and 12 weeks after dermabrasion were analyzed histologically and by in situ hybridization for fibroblast procollagen I mRNA, immunohistologically and by Western blotting with a monoclonal antibody specific for the aminoterminal cleavage site of procollagen I. RESULTS: Masson's trichrome staining demonstrated an increase in collagen from baseline (as an upper dermal band in the dermabrasion "repair zone") at 3 and 12 weeks' postdermabrasion. Immunohistologic examination demonstrated papillary dermal fibroblast staining for procollagen I at baseline that increased by threefold at 3 weeks' postdermabrasion and by 1.5-fold at 12 weeks' postdermabrasion. Western blotting demonstrated an average-fold increase in pN collagen I of 4.2 +/- 1.5 at 3 weeks and of 2.7 +/- 0.7 at 12 weeks. By in situ hybridization, baseline levels of procollagen I mRNA in papillary dermal fibroblasts increased sixfold at weeks 3 and 12 postdermabrasion. Increase in procollagen I mRNA correlated with clinical improvement, ie, reduction in wrinkling. CONCLUSION: Superficial dermabrasion clinically improves photoaged skin, and this improvement correlates strongly with increased collagen I gene expression.
The ability of an animal to cope with new environments arises from its capacity to respond to environmental variables and maintain body equilibrium (homeostasis). Each compensating mechanism depends on, and is a part of, a physiological feedback process. The severity (intensity and duration) of an environmental change relative to the animal's capacity to respond determines the potential disruption to the animal's equilibrium and the resources that must be invested to regain homeostasis. However, an environmental change sufficient to seriously challenge one individual may be insufficient to produce a measurable response in another. The principles behind the responses occurring in animals as a consequence of a change in their physical environment are illustrated in this review by examples drawn from responses of animals to cold stress. Behavioral opportunities sometimes are constrained in farm animals, and internal metabolic responses tend to become more prominent in such situations. Furthermore, as a disturbing factor persists, the immediate defensive responses are replaced by longer-term and adaptive mechanisms that reduce the burden on the animal. As we gain greater understanding of the environment-animal interface and the sensitivity and response of animals to disruption, we will be better able to establish and maintain suitable environments for our farm animals.
Multiple symmetrical lipomatosis is a rare disorder of fat distribution which generally affects middle age men of Mediterranean origin. Hürthle cell carcinoma is an uncommon variety of follicular carcinoma which invades locally and metastasizes hematogenously to bone, lung, and other distant organs. This report describes a patient who developed multiple symmetrical lipomatosis after undergoing total thyroidectomy for Hürthle cell carcinoma of the thyroid. Type IV hyperlipidemia, hyperuricemia, frequent ethanol usage, and macrocytosis were features previously associated with multiple symmetrical lipomatosis which were present in this patient. Fourteen years after the initial surgery, metastatic Hürthle cell carcinoma was detected in the superior mediastinum. The location of the metastasis and the long disease free interval are unusual features of this case. A possible association between Hürthle cell carcinoma and multiple symmetrical lipomatosis is considered.
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