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排序方式: 共有1014条查询结果,搜索用时 31 毫秒
1.
Ying Qian Pedram Hamrah Florence Boisgerault Satoru Yamagami Sudhir Vora Gilles Benichou M Reza Dana 《Journal of interferon & cytokine research》2002,22(12):1217-1225
This study aimed to determine the effects of anti-CD154 on T cell cytokine profiles and ocular chemokine gene expression after high-risk corneal transplantation and to specifically determine if CD154 blockade is associated with a switch from a Th1 to a Th2 alloimmune response. Mice were used as recipients of syngeneic or multiple minor H or MHC antigen-mismatched corneal grafts. Recipient beds were neovascularized (high-risk). Hosts were randomized to receive either anti-CD154 antibody or control immunoglobulin (Ig) perioperatively. Two weeks after corneal transplantation, allospecific delayed-type hypersensitivity (DTH) was evaluated. Frequencies of interferon-gamma (IFN-gamma)-, interleukin-2 (IL-2)-, IL-4-, and IL-5-secreting T cells in the hosts were measured by enzyme-linked immunospot (ELISPOT) assay. Ocular chemokine gene expression in anti-CD154-treated and control hamster Ig-treated groups was determined using a multiprobe ribonuclease protection assay (RPA). Leukocyte infiltration of corneal grafts was evaluated microscopically. Anti-CD154-treated mice did not exhibit allospecific DTH. The frequencies of Th1 cytokine-producing but not Th2 cytokine-producing T cells were significantly reduced in anti-CD154-treated hosts. Postoperative mRNA levels of RANTES and macrophage inflammatory protein-1beta (MIP-1beta) in anti-CD154-treated eyes were substantially suppressed compared with hamster Ig-treated controls. Leukocyte infiltration was profoundly suppressed in grafts of anti-CD154-treated hosts. These data demonstrate that blockade of the CD40-CD154 costimulatory pathway after corneal transplantation inhibits Th1-mediated responses but does not induce a switch to a Th2-specific response. In addition, anti-CD154 therapy suppresses ocular chemokine gene expression and leukocytic infiltration into allografts. 相似文献
2.
Swartz MJ Batra SK Varshney GC Hollingsworth MA Yeo CJ Cameron JL Wilentz RE Hruban RH Argani P 《American journal of clinical pathology》2002,117(5):791-796
Pancreatic adenocarcinoma is believed to develop from histologically identifiable intraductal lesions known as pancreatic intraepithelial neoplasias (PanINs) that undergo a series of architectural, cytologic, and genetic changes, a progression model similar to the adenoma-carcinoma sequence in the colon. The apomucin MUC4 has been implicated in invasive pancreatic adenocarcinoma. MUC4 expression is not detectable at the RNA level in normal pancreas but is detectable at high levels in invasive pancreatic adenocarcinoma. We documented the pattern of expression of MUC4 in PanINs by studying a series of 71 PanIN lesions immunohistochemically using a new monoclonal antibody to MUC4. Five (17%) of 30 PanIN-1 lesions, 10 (36%) of 28 PanIN-2 lesions, 11 (85%) of 13 PanIN-3 lesions, and 25 (89%) of 28 invasive adenocarcinomas labeled with the MUC4 antibody used in the study. In addition, afew nonneoplastic lesions labeled with the MUC4 antibody, including reactive ducts in chronic pancreatitis, atrophic ducts filled with inspissated secretions, and ducts showing squamous metaplasia. Our data help establish the patterns of MUC4 expression in neoplastic precursors in the pancreas and add further support to the progression model for pancreatic adenocarcinoma. 相似文献
3.
Telomere lengths of translocation-associated and nontranslocation-associated sarcomas differ dramatically
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Montgomery E Argani P Hicks JL DeMarzo AM Meeker AK 《The American journal of pathology》2004,164(5):1523-1529
Sarcomas can be divided into those with specific translocations displaying monotonous cytomorphology, and those with complex karyotypes and marked cellular pleomorphism. Telomeres contain terminal DNA sequence repeats that maintain chromosomal stability. Telomeres shorten with cell division and may become dysfunctional leading to chromosomal instability. Using a fluorescence in situ hybridization/immunofluorescence method to assess telomere lengths in archival tissues we analyzed these two types of sarcomas using paraffin-embedded primary tumor specimens. Tissues from nine sarcomas with characteristic translocations (two synovial sarcomas, two alveolar rhabdomyosarcomas, two desmoplastic round cell tumors, and one each of infantile fibrosarcoma, myxoid liposarcoma, cellular congenital mesoblastic nephroma) and nine without (four malignant fibrous histiocytomas, two leiomyosarcomas, one pleomorphic rhabdomyosarcoma, one dedifferentiated chondrosarcoma, and one malignant peripheral nerve sheath tumor) were analyzed. In all (nine of nine) cases with specific translocations, which generally have few karyotypic abnormalities, telomere lengths were similar to or reduced compared to surrounding nonneoplastic tissues. In contrast, telomeres in cases lacking specific translocations, which generally contain complex karyotypes, were often found to be dramatically lengthened and heterogeneous. In addition to markedly elongated telomeres, seven of nine (78%) complex cases exhibited large brightly stained regions corresponding to a specific type of promyelocytic leukemia nuclear body found in immortalized cells that maintain telomeres in a telomerase-independent manner [alternative lengthening of telomeres (ALT) pathway]. This phenotype is unlike that of epithelial neoplasms that typically display complex karyotypes with abnormally short telomeres maintained by the enzyme telomerase. The discovery of heterogeneous telomere lengths and evidence of the ALT pathway in the majority of sarcomas with complex karyotypes supports the existence of a telomere maintenance pathway incapable of full karyotypic stabilization in pleomorphic sarcomas. These findings provide additional molecular-genetic evidence supporting the dichotomous grouping of sarcomas into those with characteristic signature translocations without extensive additional karyotypic abnormalities, and those without such signature translocations that typically display very complex karyotypes, and point to telomere dysfunction as a plausible contributor to the chromosomal aberrations found in complex sarcomas. 相似文献
4.
The V599E BRAF mutation is uncommon in biliary tract cancers. 总被引:1,自引:0,他引:1
David Goldenberg Eli Rosenbaum Pedram Argani Ignacio I Wistuba David Sidransky Paul J Thuluvath Manuel Hidalgo Joseph Califano Anirban Maitra 《Modern pathology》2004,17(11):1386-1391
Activating point mutations of the BRAF oncogene have been identified in several solid tumors, most commonly in cutaneous melanomas and papillary carcinomas of the thyroid. A specific point mutation--V599E--accounts for the overwhelming majority of these mutational events. We explored the frequency of the V599E BRAF mutation in biliary tract cancers. In all, 62 archival biliary tract cancers, including 15 gallbladder cancers, 15 extrahepatic, and 10 intrahepatic cholangiocarcinomas from the United States, and 22 gallbladder carcinomas from Chile were analyzed for the V599E mutation of the BRAF gene using three distinct methods: direct sequencing, a primer extension method (Mutector assay), and the highly sensitive quantitative Gap Ligase Chain Reaction. The common V599E mutation was not identified in any of the 62 biliary cancer samples using these three methods of detection. The V599E somatic mutation of the BRAF gene is absent in biliary tract cancers, at least in the two geographic populations (United States and Chile) examined. Activation of the RAS/RAF/MAP kinase pathway in biliary tract cancers is likely to be secondary to oncogenic RAS mutations, or due to mutations of the BRAF gene at nucleotide positions not explored in the current study. 相似文献
5.
Exposure of neocortical slices to progesterone, without prior treatment with estrogen, augmented forskolin-induced cyclic AMP within 15 min. 30 nM progesterone produced approximately 1/2 the maximal effect but as little as 10 nM progesterone produced a detectable increase in cyclic AMP. When forskolin was replaced by dideoxyforskolin, an analog that does not directly stimulate adenylyl cyclase but shares many of its other actions, progesterone did not augment cyclic AMP. Progesterone also failed to affect increased cyclic AMP that followed exposure to norepinephrine or isoproterenol. The effect of progesterone upon cyclic AMP was also evident when tetrodotoxin was added to block voltage-dependent sodium channels, suggesting that intercellular communication that is dependent upon action potentials was not necessary. The effect of progesterone was at least partially blocked by antagonists of GABAA receptor action, suggesting the involvement of GABAA or GABAA-like receptors. The effect of progesterone was also not homogeneous over the neo cortex. While forskolin-stimulated cyclic AMP was augmented by progesterone in the parietal and occipital regions, it was suppressed in the frontal region. These results are envisioned as a progesterone action upon a small and perhaps compartmentalized component of the cellular cyclic AMP system, an effect that is made detectable in our whole-tissue assay by the well known ability of forskolin to potentiate many hormonal effects upon cyclic AMP. 相似文献
6.
OBJECTIVES: Portfolio theory has been suggested as a means to improve the risk-return characteristics of investments in health-care programs through diversification when costs and effects are uncertain. This approach is based on the assumption that the investment proportions are not subject to uncertainty and that the budget can be invested in toto in health-care programs. METHODS: In the present paper we develop an algorithm that accounts for the fact that investment proportions in health-care programs may be uncertain (due to the uncertainty associated with costs) and limited (due to the size of the programs). The initial budget allocation across programs may therefore be revised at the end of the investment period to cover the extra costs of some programs with the leftover budget of other programs in the portfolio. RESULTS: Once the total budget is equivalent to or exceeds the expected costs of the programs in the portfolio, the initial budget allocation policy does not impact the risk-return characteristics of the combined portfolio, i.e., there is no benefit from diversification anymore. CONCLUSION: The applicability of portfolio methods to improve the risk-return characteristics of investments in health care is limited to situations where the available budget is much smaller than the expected costs of the programs to be funded. 相似文献
7.
8.
Hekmat M Rafieyian S Foroughi M Majidi Tehrani MM Beheshti Monfared M Hassantash SA 《Asian cardiovascular & thoracic annals》2005,13(4):307-310
Coronary artery anomalies are common among patients with tetralogy of Fallot. One hundred and thirty-five patients (80 males and 55 females) with tetralogy of Fallot who underwent repair between 1995 and 2002 were studied to determine the incidence of coronary anomalies in Iranian patients. Eight (5.9%) patients (4 males and 4 females) had a surgically relevant coronary artery anomaly: single coronary ostium in 5, origin of the left anterior descending artery from the right coronary artery in 2, and origin of the right coronary artery from the left coronary artery in 1. The surgical technique in 3 of these patients was repair of the ventricular septal defect with a transverse incision on the right ventricle, without damage to the coronary arteries. In another patient, an allograft aortic valve cylinder was inserted. In the other 4 patients with a single coronary ostium, placement of a limited transannular patch was adequate. Consideration of these anomalies during primary repair could decrease the risk of operation in such patients. However, it seems that the presence of anomalous coronary arteries does not affect incremental risk after surgical repair. 相似文献
9.
The concept of food addiction (FA) is a potentially important contributing factor to the development of obesity in the general population; however, little is known about the hormonal and dietary differences between obesity with and without FA. Therefore, the aim of our study was to explore potential biomarkers, including various hormones and neuropeptides, which regulate appetite and metabolism, and dietary components that could potentially differentiate obesity with and without FA. Of the 737 adults recruited from the general Newfoundland population, 58 food-addicted and non-food-addicted overweight/obese individuals (FAO, NFO) matched for age, sex, BMI and physical activity were selected. A total of 34 neuropeptides, gut hormones, pituitary polypeptide hormones and adipokines were measured in fasting serum. We found that the FAO group had lower levels of TSH, TNF-α and amylin, but higher levels of prolactin, as compared to NFO group. The total calorie intake (per kg body weight), the dietary intake of fat (per g/kg body weight, per BMI and per percentage of trunk fat) and the percent calorie intake from fat and carbohydrates (g/kg) was higher in the FAO group compared to the NFO group. The FAO subjects consumed more sugar, minerals (including sodium, potassium, calcium and selenium), fat and its components (such as saturated, monounsaturated and trans fat), omega 3 and 6, vitamin D and gamma-tocopherol compared to the NFO group. To our knowledge, this is the first study indicating possible differences in hormonal levels and micro-nutrient intakes between obese individuals classified with and without food addiction. The findings provide insights into the mechanisms by which FA could contribute to obesity. 相似文献
10.