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2.
Kevil CG Hicks MJ He X Zhang J Ballantyne CM Raman C Schoeb TR Bullard DC 《The American journal of pathology》2004,165(2):609-616
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune complex-mediated tissue injury. Many different adhesion molecules are thought to participate in the development of SLE; however, few studies have directly examined the contributions of these proteins. Here we demonstrate that LFA-1 plays an essential role in the development of lupus in MRL/MpJ-Fas(lpr) mice. Mice deficient in LFA-1, but not Mac-1, showed significantly increased survival, decreased anti-DNA autoantibody formation, and reduced glomerulonephritis. The phenotype of the LFA-1-deficient mice was similar to that observed in beta(2) integrin-deficient (CD18-null) MRL/MpJ-Fas(lpr) mice, suggesting a lack of redundancy among the beta(2) integrin family members and other adhesion molecules. These studies identify LFA-1 as a key contributor in the pathogenesis of autoimmune disease in this model, and further suggest that therapeutic strategies targeting this adhesion molecule may be beneficial for the treatment of SLE. 相似文献
3.
Hagood JS Prabhakaran P Kumbla P Salazar L MacEwen MW Barker TH Ortiz LA Schoeb T Siegal GP Alexander CB Pardo A Selman M 《The American journal of pathology》2005,167(2):365-379
Fibroblasts consist of heterogeneous subpopulations that have distinct roles in fibrotic responses. Previously we reported enhanced proliferation in response to fibrogenic growth factors and selective activation of latent transforming growth factor (TGF)-beta in fibroblasts lacking cell surface expression of Thy-1 glycoprotein, suggesting that Thy-1 modulates the fibrogenic potential of fibroblasts. Here we report that compared to controls Thy-1-/- C57BL/6 mice displayed more severe histopathological lung fibrosis, greater accumulation of lung collagen, and increased TGF-beta activation in the lungs 14 days after intratracheal bleomycin. The majority of cells demonstrating TGF-beta activation and myofibroblast differentiation in bleomycin-induced lesions were Thy-1-negative. Histological sections from patients with idiopathic pulmonary fibrosis demonstrated absent Thy-1 staining within fibroblastic foci. Normal lung fibroblasts, in both mice and humans, were predominantly Thy-1-positive. The fibrogenic cytokines interleukin-1 and tumor necrosis factor-alpha induced loss of fibroblast Thy-1 surface expression in vitro, which was associated with Thy-1 shedding, Smad phosphorylation, and myofibroblast differentiation. These results suggest that fibrogenic injury promotes loss of lung fibroblast Thy-1 expression, resulting in enhanced fibrogenesis. 相似文献
4.
Mouse hepatitis virus strain UAB infection enhances resistance to Salmonella typhimurium in mice by inducing suppression of bacterial growth. 总被引:2,自引:2,他引:2
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We have previously shown that intranasal infection of mice with mouse hepatitis virus (MHV) strain UAB (MHV-UAB) increases their resistance to Salmonella typhimurium injected intravenously 6 days later. To study how salmonella resistance was induced, BALB/cAnNCr mice were infected with salmonella strains carrying specific genetic alterations. One set of studies compared the effect of MHV infection on subsequent salmonella infections with AroA- (avirulent) and Aro+ (virulent) salmonellae. Unlike its effect on Aro+ salmonellae, MHV failed to reduce the number of AroA- salmonellae recovered from mice. Because AroA- S. typhimurium shows almost no growth in vivo, this failure indicated that the effect of MHV on salmonella resistance required growth of the infecting salmonellae. In other studies, the effect of MHV infection on both growth and killing were monitored simultaneously in mice with growing salmonellae carrying a single copy of the temperature-sensitive pHSG422 plasmid, which is unable to replicate in vivo. MHV infection reduced salmonella growth but caused no increase in salmonella killing. MHV infection of mice given wild-type salmonellae also resulted in no increase in salmonella killing 4 h after salmonella challenge. These studies demonstrate that MHV-UAB infection increases host resistance to salmonellae by enhancing suppression of bacterial growth instead of by increasing the amount of salmonella killing. 相似文献
5.
Modulation of resistance to Salmonella typhimurium infection in mice by mouse hepatitis virus (MHV) 总被引:5,自引:0,他引:5
Prior infection of mice with a field strain of mouse hepatitis virus (MHV) increased the early resistance of euthymic mice to virulent Salmonella typhimurium strain SR-11 infections (as defined by significantly fewer salmonella colony-forming units (cfu) present in spleens and livers 4 days after salmonella infection). This increase in salmonella resistance was observed when the interval between MHV and salmonella infections was 6 days, but not at 3, 10, or 14 day intervals. The mouse Ity locus, which controls the number of intracellular salmonella, had a significant effect on the ability of MHV to induce resistance to salmonella. MHV caused an increase in resistance to salmonella in Itys (salmonella susceptible) mice at all doses of salmonella tested (100 to 10,000 cfu). In the Ityr (salmonella resistant) mice tested the beneficial effect of MHV on salmonella resistance was small and when observed, was only present at salmonella doses of 10,000 cfu or greater. Neither the Lpsd nor Xid mutations affected the ability of MHV to increase resistance to salmonella infection. In contrast to euthymic mice, MHV infection greatly decreased the resistance of athymic (nude) mice to salmonella infection. Since the Nu locus does not affect the resistance of mice to salmonella (at 4 days post salmonella infection), these results indicate that MHV infection and the nude phenotype interact to increase susceptibility to salmonella. These findings re-emphasize the importance of keeping laboratory mice used in research free of MHV and other immunomodulatory pathogens. 相似文献
6.
Terry?O?Herndon Salvador?Gonzalez TR?Gowrishankar R?Rox?Anderson James?C?WeaverEmail author 《BMC medicine》2004,2(1):12
Background
Painless, rapid, controlled, minimally invasive molecular transport across human skin for drug delivery and analyte acquisition is of widespread interest. Creation of microconduits through the stratum corneum and epidermis is achieved by stochastic scissioning events localized to typically 250 μm diameter areas of human skin in vivo. 相似文献7.
Intracage ammonia promotes growth of Mycoplasma pulmonis in the respiratory tract of rats. 总被引:1,自引:5,他引:1
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Ammonia (NH3) from soiled cage bedding is known to enhance the progression and severity of murine respiratory mycoplasmosis in rats. To test the hypothesis that NH3 directly or indirectly enhances the growth of Mycoplasma pulmonis in vivo, pathogen-free F344 rats were inoculated intranasally with 1 x 10(4) to 4 x 10(4) or 4 x 10(6) to 5 x 10(6) colony-forming units of M. pulmonis and exposed to less than or equal to 1.5 or 76 microgram of NH3 per liter (less than or equal to 2 or 100 ppm, respectively). Nasal passages, larynges, tracheas, and lungs from rats killed at intervals up to 28 days after inoculation were quantitatively cultured. Growth of M. pulmonis was much greater in NH3-exposed rats than in controls, particularly in those inoculated with the lower dose. Increases in M. pulmonis populations were more rapid in proximal airways than in distal airways. Serum immunoglobulin G and M antibody responses to M. pulmonis as measured by an enzyme-linked immunosorbent assay were greater in NH3-exposed rats. In other experiments, the nasal passages absorbed virtually all NH3 when the rats were exposed to less than 380 micrograms of NH3 per liter (500 ppm), indicating that NH3 induced increases in the numbers of organisms in the distal respiratory tract, probably by a secondary, rather than a direct, effect. Also, NH3 exposure did not inhibit pulmonary antibacterial activity as measured by clearance of radiolabeled Staphylococcus epidermidis. The growth of M. pulmonis in vitro was inhibited by 1 mM NH4+ added to the medium as NH4OH but not by NH4+ concentrations of 0.5, 0.1, or 0.01 mM, suggesting that NH3 increases growth indirectly through effects on the host. 相似文献
8.
Eighty four out of 2151 militancy trauma patients sustained severe maxillofacial injury from Jan 1990 to March 1993. The resuscitation, stabilisation and intensive care of these patients was based on management priorities of primary resuscitation, care of airway, management of haemodynamics, oxygenation and monitoring. Anaesthesia was administered in a situation when the airway was likely to be compromised and the patients were critically sick. Initial ventilation and oxygenation was the most difficult and could be achieved with satisfactory seal around the face mask by applying water-soaked guaze pieces around the mouth and nose to “fill-in” the defects. Tracheal intubation could be accomplished with intravenous sedation by an experienced anaesthesiologist. Dental occlusion and wiring necessiated the placement of nasotracheal tube for 48-72 hours after surgery.KEY WORDS: Trauma, Maxillofacial injury, Trauma anesthesia, Anaesthesia and critical care 相似文献
9.
OBJECTIVE: Because survival from admission to discharge does not provide parents and physicians information about future life expectancy in the premature neonate, we characterized the actuarial survival, defined as the future life expectancy from a given postnatal age, in a large inborn population of premature infants < 30 weeks' gestation. STUDY DESIGN: We determined daily actuarial survival of 1925 inborn infants (23 to 29 weeks' gestation) admitted to the Baylor Affiliated Nurseries from July 1986 through December 1994, stratified by 100-g birth weight and by 1-week gestational-age intervals. RESULTS: In the 501- to 600-g birth weight stratum, actuarial survival improved from 31% at birth, to 61% on day of life 7, and then to 75% on day of life 28; in the 901- to 1000-g birth weight stratum, actuarial survival improved from 88%, to 94%, and then to 98% throughout the same times, respectively. Similar trends were obtained when data were stratified by gestational age. CONCLUSIONS: Survival in the smallest infants improves dramatically during the first few days of life, but there is a significant risk for late death in the smallest of these infants. 相似文献
10.
Gonzales AJ; Christensen JG; Preston RJ; Goldsworthy TL; Tlsty TD; Fox TR 《Carcinogenesis》1998,19(7):1173-1183