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11.
T cell immunity is the key to protective immune responses against tumors. Traditionally, this function has been ascribed to CD8 T lymphocytes with cytotoxic activity, which are restricted by MHC class I molecules. In recent years the realization that CD4 T cells can also play a relevant role in protective anti-tumor responses has received growing attention. Here we will discuss the role of MHC class II-restricted T cells in response to, and in the regulation of, tumor antigens. Emphasis will be placed on four areas: (1) the role of CD4 T cell immunity in tumor protection in animal models and putative mode of action, (2) tumor antigens recognized by human CD4 T cells, (3) the cooperation between two CD4 T cells of different specificity as a new way to jump start the response against sub-immunogenic determinants of tumor antigens in a tolerant environment, and (4) the negative impact of regulatory CD4 T cells on anti-tumor T cell responses. By drawing attention to these four areas, it is our intention to provide the reader with a comprehensive view of issues of contemporary importance for this field, in the expectation that the information will help a better design of therapeutic cancer vaccines. 相似文献
12.
Pepe C Foley S Shannon J Lemiere C Olivenstein R Ernst P Ludwig MS Martin JG Hamid Q 《The Journal of allergy and clinical immunology》2005,116(3):544-549
BACKGROUND: Airway remodeling in asthma comprises a range of structural changes. Several studies have suggested an association between these changes and disease severity. The relationship between the extent of remodeling and lung function is not well defined. OBJECTIVE: We sought to contrast the structural changes in the airways of well-defined groups of subjects with severe and moderate asthma and to correlate the extent of remodeling with disease severity. METHODS: Endobronchial biopsy specimens were obtained from 15 subjects with severe and 13 subjects with moderate asthma. Epithelial integrity, cell-layer areas, subepithelial fibrosis, and the distance between epithelial and airway smooth muscle (ASM) layers were measured by means of image analysis. Collagen was identified by using Van Giesen stain, and ASM was defined by using smooth muscle alpha-actin immunostaining. Specific immunostains were performed for the evaluation of RANTES, IL-8, and eotaxin expression as markers of ASM phenotype. RESULTS: ASM area was greater in subjects with severe (0.24+/- 0.03 mm(2)) than in subjects with moderate (0.05+/- 0.01 mm(2)) asthma (P<.001). The distance between the epithelial and ASM layers was less in the severe group (0.12+/- 0.01 mm) than in the moderate group (0.24+/- 0.02, P<.001). A trend toward greater subepithelial fibrosis in subjects with severe asthma did not reach statistical significance. IL-8 and eotaxin expression, but not RANTES expression, were increased in the ASM of subjects with severe asthma compared with in subjects with moderate asthma. CONCLUSION: Smooth muscle alteration is the key structural change that distinguishes severe from moderate asthma, and phenotypic change in ASM might contribute to the difficulty in obtaining adequate control in some subjects with severe asthma. 相似文献
13.
Dina Ruano António Macedo Maria Jo?o Soares José Valente Maria Helena Azevedo Carlos Pato Mara Helena Hutz Clarissa S Gama Maria Inês Lobato Paulo Belmonte-de-Abreu Peter Heutink Joana Almeida Palha 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2007,(5):642-646
Several observations point to the involvement of disturbed lipid biology in schizophrenia. Reduced response to niacin flushing test, which involves vasodilatation induced by prostaglandin D2 (PGD2), is among the evidences, together with decreased CSF levels of lipocalin-type prostaglandin D2 synthase (PTGDS), the enzyme responsible for the synthesis of PGD2 in the brain. Since PTGDS is also a carrier for lipophilic molecules such as retinoids and thyroid hormones, altered PTGDS levels might influence both PGD2-mediated signaling, and vitamin A and thyroid hormone availability. To test whether genetic variants of PTGDS are involved in the etiology of schizophrenia, we searched for variants in the coding and regulatory regions of the gene. We identified four previously described polymorphisms. Using two case-control samples from Portugal and Brazil, none of the polymorphisms tested was associated with the disease. In addition, no transmission distortion was observed in an independent parents-offspring sample from the Azorean Islands. Our data do not support the involvement of the PTGDS gene in the etiology of schizophrenia. 相似文献
14.
Sastre J Lluch-Bernal M Quirce S Arrieta I Lahoz C Del Amo A Fernández-Caldas E Marañón F 《Allergy》2000,55(6):560-564
BACKGROUND: The third-stage larvae of Anisakis simplex may be a hidden source of allergens in fish. The objective was to determine whether the ingestion of lyophilized A. simplex larvae, or antigen, induces clinical symptoms in a group of A. simplex-sensitized patients. METHODS: Double-blind, placebo-controlled oral challenges were conducted in 11 individuals who had experienced allergic reactions after eating fish. Another patient had chronic urticaria unrelated to the ingestion of fish. All patients had positive skin tests and specific IgE determinations for A. simplex and negative skin tests to a battery of fish species. Conjunctival tests with A. simplex extracts were conducted in all patients and in five controls. The 12 patients received capsules containing either lactose or one, five, or 25 lyophilized larvae of A. simplex at 2-h intervals in a double-blind fashion. The highest single dose was 100 larvae. ECP and tryptase levels in serum were measured before and after the last oral challenge. Lyophilized antigen was also given to five patients. RESULTS: None of the 12 patients experienced a positive reaction after the ingestion of the placebo, the lyophilized larvae, or the antigen. Tryptase and ECP levels before and after challenges did not change significantly. Conjunctival provocation tests were positive in 11 out of the 12 patients and in none of the controls. CONCLUSIONS: The ingestion of 100 lyophilized A. simplex larvae, or its equivalent in antigen, does not induce clinical symptoms in individuals with a clinical history and laboratory findings of hypersensitivity to A. simplex. The data suggest that only the ingestion of live larvae may be capable of inducing allergic manifestations. 相似文献
15.
Maria do Carmo Debur Juliano Bordignon Claudia Nunes Duarte dos Santos Luine Rosele Vidal Meri Bordignon Nogueira Sérgio Monteiro de Almeida Sonia Mara Raboni 《Journal of clinical virology》2007,39(1):59-62
BACKGROUND: Human metapneumovirus (hMPV) has been described as an etiologic agent of acute respiratory infections (ARI), mainly in pediatric patients. Viral isolation is difficult and has low sensitivity, and consequently RT-PCR assays are currently used for detection. OBJECTIVES: Detect hMPV in ARI in hospitalized children in Southern Brazil; standardize a RT-PCR for routine hMPV diagnosis; validate a positive control for molecular tests; and perform phylogenetics analyses. STUDY DESIGN: Nasopharyngeal aspirates (NPA) from 156 hospitalized children were studied. A conserved region of the nucleoprotein gene was cloned, characterized and used to standardize an RT-PCR assay. Phylogenetic analyses were performed. Clinical data were obtained from medical records. RESULTS: hMPV was detected in 6.4% of the samples. Dyspnea and wheezing were frequently reported symptoms and the most common diagnoses were bronchiolitis, acute respiratory insufficiency or laryngotracheobronchitis. Nucleotide sequence alignment revealed 97.7% identity with genotype A1 of hMPV. The detection limit of hMPV genomes by RT-PCR in clinical samples was 180 copies/microL. CONCLUSION: This is the first report of the detection and genetic characterization of hMPV infections in children with lower ARI in Southern Brazil. 相似文献
16.
Mara L. Leimanis-Laurens Karen Ferguson Emily Wolfrum Brian Boville Dominic Sanfilippo Todd A. Lydic Jeremy W. Prokop Surender Rajasekaran 《Nutrients》2021,13(3)
Lipids are molecules involved in metabolism and inflammation. This study investigates the plasma lipidome for markers of severity and nutritional status in critically ill children. Children with multi-organ dysfunction syndrome (MODS) (n = 24) are analyzed at three time-points and cross-referenced to sedation controls (n = 4) for a total of N = 28. Eight of the patients with MODS, needed veno-arterial extracorporeal membrane oxygenation (VA ECMO) support to survive. Blood plasma lipid profiles are quantified by nano-electrospray (nESI), direct infusion high resolution/accurate mass spectrometry (MS), and tandem mass spectrometry (MS/MS), and compared to nutritional profiles and pediatric logistic organ dysfunction (PELOD) scores. Our results show that PELOD scores were not significantly different between MODS and ECMO cases across time-points (p = 0.66). Lipid profiling provides stratification between sedation controls and all MODS patients for total lysophosphatidylserine (lysoPS) (p-value = 0.004), total phosphatidylserine (PS) (p-value = 0.015), and total ether-linked phosphatidylethanolamine (ether-PE) (p-value = 0.03) after adjusting for sex and age. Nutrition intake over time did not correlate with changes in lipid profiles, as measured by caloric and protein intake. Lipid measurement in the intensive care environment shows dynamic changes over an 8-day pediatric intensive care unit (PICU) course, suggesting novel metabolic indicators for defining critically ill children. 相似文献
17.
Neves Lia Mara Grosso Tim Carla Roberta Floriano Elaine Medeiros da Silva de Avó Lucimar Retto Fernandes João Batista Parizotto Nivaldo Antonio Cominetti Marcia Regina 《Lasers in medical science》2021,36(4):863-870
Lasers in Medical Science - Ultraviolet radiation (UVR) is the major etiologic agent of cutaneous photoaging, and different strategies are used to prevent and treat this condition. The... 相似文献
18.
Di Rienzo Alessandro Colasanti Roberto Gladi Maurizio Dobran Mauro Della Costanza Martina Capece Mara Veccia Salvatore Iacoangeli Maurizio 《Neurosurgical review》2021,44(3):1523-1532
Neurosurgical Review - The optimal management of cranioplasty infections remains a matter of debate. Most authors have suggested that the infected bone/implant removal is mandatory, combined with... 相似文献
19.
Joshua R. Harmer Cody C. Wyles Kristin C. Mara Nafisseh S. Warner Robert T. Trousdale 《The Journal of arthroplasty》2021,36(2):532-536
BackgroundInadequate pain control following total knee arthroplasty (TKA) has been postulated to negatively impact knee range of motion (ROM). We sought to determine the association between perioperative pain levels and knee ROM at 3-month follow-up or need for manipulation under anesthesia (MUA).MethodsWe retrospectively reviewed 2243 primary TKAs performed from 2002 to 2019 at a single academic center using an institutional total joint registry. Mean age was 68, mean body mass index was 32.8, and 59% were female. Knee ROM was measured preoperatively and 3 months postoperatively. Change in knee ROM, rates of soft tissue contracture, and MUA were assessed in relation to in-hospital 10-point pain visual analog scale (VAS) measurements.ResultsOverall, 44% had improved ROM at 3-month follow-up, 29% had no change in ROM, and 27% had worsened ROM. There was no significant difference in mean VAS scores of patients with improved, unchanged, or worsened ROM postoperatively (3.0 vs 2.8 vs 3.0; P = .068). There was no significant difference in mean VAS scores of patients who developed a soft tissue contracture or required MUA vs those who did not develop these complications (2.7 vs 2.9; P = .24). Similarly, no significant relationship with these outcomes was identified when maximum and discharge VAS scores were analyzed.ConclusionComparable ROM and rates of MUA based on in-hospital pain levels were observed in this large series of primary TKA patients. While significant early pain may limit participation in ROM exercises initially, this does not appear to have a marked impact on ROM-related complications for most patients.Level of EvidenceIII, Therapeutic. 相似文献