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991.
992.
Introcaso CE Leber B Greene K Ubriani R Rook AH Kim EJ 《Journal of the American Academy of Dermatology》2008,58(4):645-649
Cutaneous T-cell lymphomas are a type of indolent non-Hodgkin's lymphoma where patients with limited skin disease can be successfully treated with a variety of skin-directed, systemic, and immunomodulating therapies, whereas durable remissions are difficult to achieve in patients with tumor, erythrodermic, or systemic disease. We describe a patient with cutaneous T-cell lymphoma and malignant cells constituting 99% of her peripheral blood lymphocytes who had a sustained complete response after an HLA-matched sibling allogeneic stem cell transplantation. We also review the current literature regarding both autologous and allogeneic stem cell transplantations for advanced stages of cutaneous T-cell lymphoma, discuss the importance of the graft-versus-tumor immunomodulatory effect in successful transplantations, and suggest that allogeneic stem cell transplantation deserves further consideration and study as a potential treatment for selected patients who are younger and at high risk. 相似文献
993.
Genetic stability of the live attenuated Bordetella pertussis vaccine candidate BPZE1 总被引:1,自引:0,他引:1
Despite the extensive use of efficacious pertussis vaccines, Bordetella pertussis infections are still among the main causes for childhood morbidity and mortality. Severe pertussis occurs mostly in very young children, often too young to be sufficiently protected by current vaccines, which require several administrations in regimens that vary between countries. Since natural infection with B. pertussis is able to induce protection, we have developed the live attenuated B. pertussis vaccine strain BPZE1 that protects mice upon a single intranasal administration. This strain was obtained by genetically inactivating pertussis toxin via two point mutations in the ptx gene, by deleting dnt encoding dermonecrotic toxin, and by replacing the B. pertussis ampG gene by Escherichia coli ampG, resulting in the removal of tracheal cytotoxin. Here, we assessed the genetic stability of BPZE1 after 20 and 27 weeks of continuous passaging in vitro and in vivo, respectively. BPZE1 was passaged 20 times in vitro and 9 times in vivo in Balb/C mice. After these passages, 8 hemolytic colonies were analyzed by PCR for the absence of dnt and B. pertussis ampG and the presence of E. coli ampG, by DNA sequencing for the presence of the two ptx point mutations and by DNA microarrays for the global genomic stability. In addition, the protective capacity of BPZE1 was evaluated after the passages. No genetic or protective difference was detected between the passaged bacteria and non-passaged BPZE1, indicating that stability of the vaccine strain is not a concern for BPZE1 to be considered as an attenuated live vaccine against whooping cough. 相似文献
994.
995.
Zhu Y Ehre C Abdullah LH Sheehan JK Roy M Evans CM Dickey BF Davis CW 《The Journal of physiology》2008,586(7):1977-1992
Since the airways of control mouse lungs contain few alcian blue/periodic acid–Schiff's (AB/PAS)+ staining 'goblet' cells in the absence of an inflammatory stimulus such as allergen sensitization, it was surprising to find that the lungs of mice deficient for the exocytic priming protein Munc13-2 stain prominently with AB/PAS under control conditions. Purinergic agonists (ATP/UTP) stimulated release of accumulated mucins in the Munc13-2-deficient airways, suggesting that the other airway isoform, Munc13-4, supports agonist-regulated secretion. Notably, however, not all of the mucins in Munc13-2-deficient airways were secreted, suggesting a strict Munc13-2 priming requirement for a population of secretory granules. AB/PAS+ staining of Munc13-2-deficient airways was not caused by an inflammatory, metaplastic-like response: bronchial–alveolar lavage leucocyte numbers, Muc5ac and Muc5b mRNA levels, and Clara cell ultrastructure (except for increased secretory granule numbers) were all normal. A Muc5b-specific antibody indicated the presence of this mucin in Clara cells of wildtype (WT) control mice, and increased amounts in Munc13-2-deficient mice. Munc13-2 therefore appears to prime a regulated, baseline secretory pathway, such that Clara cell Muc5b, normally secreted soon after synthesis, accumulates in the gene-deficient animals, making them stain AB/PAS+. The defective priming phenotype is widespread, as goblet cells of several mucosal tissues appear engorged and Clara cells accumulated Clara cell secretory protein (CCSP) in Munc13-2-deficient mice. Additionally, because in the human airways, MUC5AC localizes to the surface epithelium and MUC5B to submucosal glands, the finding that Muc5b is secreted by Clara cells under control conditions may indicate that it is also secreted tonically from human bronchiolar Clara cells. 相似文献
996.
997.
Chronic exposure to beta-blockers attenuates inflammation and mucin content in a murine asthma model
Nguyen LP Omoluabi O Parra S Frieske JM Clement C Ammar-Aouchiche Z Ho SB Ehre C Kesimer M Knoll BJ Tuvim MJ Dickey BF Bond RA 《American journal of respiratory cell and molecular biology》2008,38(3):256-262
Single-dose administration of beta-adrenoceptor agonists produces bronchodilation and inhibits airway hyperresponsiveness (AHR), and is the standard treatment for the acute relief of asthma. However, chronic repetitive administration of beta-adrenoceptor agonists may increase AHR, airway inflammation, and risk of death. Based upon the paradigm shift that occurred with the use of beta-blockers in congestive heart failure, we previously determined that chronic administration of beta-blockers decreased AHR in a murine model of asthma. To elucidate the mechanisms for the beneficial effects of beta-blockers, we examined the effects of chronic administration of several beta-adrenoceptor ligands in a murine model of allergic asthma. Administration of beta-blockers resulted in a reduction in total cell counts, eosinophils, and the cytokines IL-13, IL-10, IL-5, and TGF-beta1 in bronchoalveolar lavage, and attenuated epithelial mucin content and morphologic changes. The differences in mucin content also occurred if the beta-blockers were administered only during the ovalbumin challenge phase, but administration of beta-blockers for 7 days was not as effective as administration for 28 days. These results indicate that in a murine model of asthma, chronic administration of beta-blockers reduces inflammation and mucous metaplasia, cardinal features of asthma that may contribute to airflow obstruction and AHR. Similar to heart failure, our results provide a second disease model in which beta-blockers producing an acutely detrimental effect may provide a therapeutically beneficial effect with chronic administration. 相似文献
998.
999.
Blandine de Lauzon‐Guillain Xavier Thierry Corinne Bois Marie Bournez Camille Davisse‐Paturet Marie‐Noëlle Dufourg Claire Kersuzan Ela Ksiazek Sophie Nicklaus Hlne Vicaire Sandra Wagner Sandrine Lioret Marie Aline Charles 《Maternal & child nutrition》2019,15(4)
Previous studies have shown a high level of noncompliance with recommendations on breastfeeding duration, especially in France. The objective was to describe the association between breastfeeding initiation and duration and the statutory duration of postnatal maternity leave, the gap between the end of legal maternity leave and the mother's return to work, and maternal working time during the first year post‐partum. Analyses were based on 8,009 infants from the French nationwide ELFE cohort. We assessed the association with breastfeeding initiation by using logistic regression and, among breastfeeding women, with categories of breastfeeding duration by using multinomial logistic regression. Among primiparous women, both postponing return to work for at least 3 weeks after statutory postnatal maternity leave (as compared with returning to work at the end of the statutory period) and working less than full‐time at 1 year post‐partum (as compared with full‐time) were related to higher prevalence of breastfeeding initiation. Among women giving birth to their first or second child, postponing the return to work until at least 15 weeks was related to a higher prevalence of long breastfeeding duration (at least 6 months) as compared with intermediate duration (3 to <6 months). Working part‐time was also positively related to breastfeeding duration. Among women giving birth to their third child or more, working characteristics were less strongly related to breastfeeding duration. These results support extending maternity leave or working time arrangements to encourage initiation and longer duration of breastfeeding. 相似文献
1000.
John H. Won Sijo J. Parekattil Scott D. Davidson John S. Luddy Muhammad S. Choudhury Camille Mallouh Hiroshi Tazaki Sensuke Konno 《Urological research》1999,27(5):376-381
To test the possibility that urinary ammonia could be a risk factor for benign prostatic hyperplasia (BPH), we explored the
cellular effects of ammonium chloride (NH4Cl) on prostatic cancer cells used as an experimental model. Following treatment of human prostatic cancer DU-145 cells with
the varying concentrations of NH4Cl for 3 days, cell growth was inhibited by approximately 50% at 5 mM NH4Cl and almost completely inhibited at 10 mM NH4Cl. However, the individual cell size in these treated cells became approximately 2-fold larger and cellular protein content
was also up to 2.5-fold greater than in untreated cells. This protein increase appeared to result from the reduced protein
degradation, verified by metabolic labeling with [14C]valine. Western blot analysis further suggested that such reduced protein turnover could in part be due to the inactivation
of a lysosomal acid protease, cathepsin D. Taken together, these studies demonstrate NH4Cl-induced hypertrophy in prostatic cancer cells, as evidenced by the growth inhibition, cell enlargement, and cellular protein
increase. Therefore, ammonia is not an inert metabolic product; instead, its chronic effects on the prostate may ultimately
lead to significant cellular and biochemical alterations of the prostate such as BPH.
Received: 27 June 1998 / Accepted: 25 March 1999 相似文献