bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient Presentation of Naturally Processed HLA Class I Peptides by Artificial Antigen-Presenting Cells for the Generation of Effective Antitumor Responses
Authors: Hirano Naoto , Butler Marcus O. , Xia Zhinan , Berezovskaya Alla , Murray Andrew P. , Ansén Sascha , Nadler Lee M. 
Published: May 2006

AbstractAppropriate presentation of tumor-associated antigens (TAA) by antigen-presenting cells (APC) is required for the development of clinically relevant antitumor T-cell responses. One common approach, which uses APC pulsed with synthetic peptides, can sometimes generate ineffective immune responses. This failure may, in part, be attributed to the formation of HLA/synthetic pulsed peptide complexes that possess different conformations compared with those of endogenously presented peptides. In addition, endogenous peptides may undergo post-translational modifications, which do not occur with synthetic peptides. Because our goal is to induce immunity that can recognize TAA that are endogenously presented by tumors, we designed an APC that would not only express the required immunoaccessory molecules but also naturally process and present target antigenic peptides. In this study, we generated an artificial APC (aAPC) that can endogenously present any chosen HLA-A*0201 (A2)–restricted peptide by processing a fusion protein that contains a unique “LTK” sequence linked to the antigenic peptide. Proteasome-dependent processing is so effective that the presented peptide can be directly eluted from the cell surface and identified by biochemical methods. Furthermore, we found that aAPC, engineered to endogenously present peptide derived from the melanoma antigen MART1, can be used to prime and expand antitumor CTL that target MART1-expressing tumor cells in a HLA-A2-restricted manner. Our engineered aAPC could serve as an “off-the-shelf” APC designed to constitutively express class I–restricted TAA peptides and could be used to generate effective T-cell responses to treat human disease.
Tumor-Targeting Properties of Novel Antibodies Specific to the Large Isoform of Tenascin-C
Authors: Brack Simon S. , Silacci Michela , Birchler Manfred , Neri Dario 
Published: May 2006

Abstract
Background: The targeted delivery of bioactive molecules with antibodies specific to tumor-associated antigens represents a promising strategy for improving the efficacy of tumor therapy. The large isoform of tenascin-C, an abundant glycoprotein of the tumor extracellular matrix, is strongly overexpressed in adult tissue undergoing tissue remodeling, including wound healing and neoplasia, and has been implicated in a variety of different cancers while being virtually undetectable in most normal adult tissues.
Experimental Design: We have used antibody phage technology to generate good-quality human recombinant antibodies (F16 and P12) specific to the alternatively spliced domains A1 and D of the large isoform of tenascin-C. The tumor-targeting properties of F16 and P12 were assessed by biodistribution studies in tumor xenografts using the antibodies in small immunoprotein (SIP) format.
Results: SIP(F16) selectively accumulated at the tumor site with 4.5%ID/g at 24 hours in the U87 glioblastoma model but was rapidly cleared from other organs (tumor-to-organ ratios, ∼10:1). The accumulation of SIP(P12) in the tumor was lower compared with SIP(F16) and persistent levels of radioactivity were observed in the intestine.
Conclusions: These data suggest that the F16 antibody, specific to domain A1 of tenascin-C, is a promising building block for the development of antibody-based pharmaceuticals in view of its excellent tumor-targeting performance and the strong expression of the antigen in a variety of primary and metastatic tumors.
Frequency and Spectrum of Cancers in the Peutz-Jeghers Syndrome
Authors: Hearle Nicholas , Schumacher Valérie , Menko Fred H. , Olschwang Sylviane , Boardman Lisa A. , Gille Johan J.P. , Keller Josbert J. , Westerman Anne Marie , Scott Rodney J. , Lim Wendy , Trimbath Jill D. , Giardiello Francis M. , Gruber Stephen B. , Offerhaus G. Johan A. , de Rooij Felix W.M. , Wilson J.H. Paul , Hansmann Anika , Möslein Gabriela , Royer-Pokora Brigitte , Vogel Tilman , Phillips Robin K.S. , Spigelman Allan D. , Houlston Richard S. 
Published: May 2006

Abstract
Background: Although an increased cancer risk in Peutz-Jeghers syndrome is established, data on the spectrum of tumors associated with the disease and the influence of germ-line STK11/LKB1 (serine/threonine kinase) mutation status are limited.
Experimental Design: We analyzed the incidence of cancer in 419 individuals with Peutz-Jeghers syndrome, and 297 had documented STK11/LKB1 mutations.
Results: Ninety-six cancers were found among individuals with Peutz-Jeghers syndrome. The risk for developing cancer at ages 20, 30, 40, 50, 60, and 70 years was 2%, 5%, 17%, 31%, 60%, and 85%, respectively. The most common cancers represented in this analysis were gastrointestinal in origin, gastroesophageal, small bowel, colorectal, and pancreatic, and the risk for these cancers at ages 30, 40, 50, and 60 years was 1%, 9%, 15%, and 33%, respectively. In women with Peutz-Jeghers syndrome, the risk of breast cancer was substantially increased, being 8% and 31% at ages 40 and 60 years, respectively. Kaplan-Meier analysis showed that cancer risks were similar in Peutz-Jeghers syndrome patients with identified STK11/LKB1 mutations and those with no detectable mutation (log-rank test of difference χ2 = 0.62; 1 df; P = 0.43). Furthermore, the type or site of STK11/LKB1 mutation did not significantly influence cancer risk.
Conclusions: The results from our study provide quantitative information on the spectrum of cancers and risks of specific cancer types associated with Peutz-Jeghers syndrome.
Utility of a whole blood single platelet counting assay to monitor the effects of tirofiban in patients with acute coronary syndromes scheduled for coronary intervention
Authors: Siotia Anjan , Buckland Robert , Judge Heather , Sastry Padmini , Storey Robert 
Published: May 2006

SummaryThis study aimed to establish the utility of a whole-blood singleplatelet counting (WBSPC) assay, a measure of microaggregation, in monitoring the effects of tirofiban, comparing this with optical aggregometry (OA) and the Ultegra TRAP cartridge system (UTC), measures of macroaggregation. Fifty-nine patients with acute coronary syndrome scheduled for coronary angiography +/angioplasty were studied. WBSPC assay (ADP 0.3-100 µM, Sysmex KX21 analyzer), OA (ADP 20 µM) and UTC were performed: before starting tirofiban; 30 min, 4 and 24 h after starting tirofiban; and 1 and 2h after stopping tirofiban. Thirty minutes after starting tirofiban, there was substantial inhibition of platelet aggregation (40 ± 30%; WBSPC, 2 minutes after addition of ADP 30 µM) and this remained stable at 4 and 24 h. OA (86 ± 17%; inhibition of maximal aggregation,ADP 20 µM) and UTC (93 ± 7%) showed marked inhibition with less inter-individual variation. There was no significant correlation between OA and UTC results (R2 = 0.006), but fair correlation between OA and WBSPC results (R2 = 0.37). Greater inhibition of macroaggregation (OA and UTC) was seen compared to microaggregation (WBSPC) such that WBSPC was more discriminating in the therapeutic range when macroaggregation was often completely inhibited. A WBSPC assay of platelet microaggregation shows promise for monitoring GPIIb/IIIa antagonists.
A novel fibrinogen Bβ chain frameshift mutation in a patient with severe congenital hypofibrinogenaemia
Authors: Zhai Zhimin , Zhou Rongfu , Wang Xuefeng , Wang Hongli , Ding Kaiyang , Sun Zimin , Xu Xiucai , Wu Jingsheng , Ni Heyu 
Published: May 2006

SummaryCongenital afibrinogenemia and severe hypofibrinogenemia are severe bleeding disorders characterized by either undetectable or very low levels of fibrinogen in patients’ plasma and platelets. A majority of the reported cases are caused by mutations in the fibrinogen Aα chain. In this study, we identified a genetic defect in the fibrinogen Bβ-chain (FGB) underlying severe hypofibrinogenemia. The propositus frequently displayed bleeding episodes with a prolonged blood-clotting time (thrombin time > 180 s,activated partial thromboplastin time > 300 s, prothrombin time > 120 s) and had a very low level of plasma fibrinogen (1.7–1.8 mg/dl). His parents had a consanguineous marriage, and their functional and immunological fibrinogen was approximately half of the normal level.The platelet fibrinogen level of the propositus could not be detected by western blotting, and his platelet aggregation was severely impaired. DNA screening of the whole fibrinogen gene revealed a homozygous GGGG→GGG mutation at nucleotide 7969–7972 in his FGB gene. The propositus’ parents are both heterozygous for this mutation. This mutation contributes to Gly419→Val, and the 419–434 codons are frame shifted, and a stop codon is formed at codon 435.The predicted truncated Bβ-chain is 27 amino acids shorter than the normal Bβ-chain and a central β-strand in the globular βC domain is absent,which may lead to destabilization of the entire β-domain. To the best of our knowledge, this is the first report of such a mutation which is associated with severe hypofibrinogenemia.
Increased cardiovascular risk markers in obesity are associated with body adiposity: Role of leptin
Authors: Gómez-Ambrosi Javier , Salvador Javier , Silva Camilo , Pastor Carlos , Rotellar Fernando , Gil María , Cienfuegos Javier , Frühbeck Gema 
Published: May 2006

SummaryEpidemiological studies have shown that obesity is associated with increased blood concentrations of proinflammatory factors and markers of endothelial dysfunction such as fibrinogen, C-reactive protein (CRP), and von Willebrand factor (vWF). We analyzed the association of these markers with percentage of body fat (BF), and the influence of leptin in a cross-sectional study of 1,089 subjects (366 men) aged 44 (34–53) [median (interquartile range)] years, who were classified as obese or non-obese according to BF estimated by whole-body air displacement plethysmography. Obesity was defined as BF ≥ 25% in men and ≥ 35% in women. Compared with non-obese subjects (mean ± SD), obese patients had higher concentrations of fibrinogen (312± 78 vs. 342 ± 81 mg/dl, P < 0.001), CRP (0.41 ± 0.75 vs. 0.75± 1. 04 mg/l, P = 0.014), vWF (107 ± 29 vs. 123 ± 55%, P < 0.001), and leptin (10.4 ± 6.5 vs. 37.5 ± 26. 1 ng/ml, P < 0.0001). A positive correlation was observed between BF and fibrinogen (r = 0.266; P < 0.0001), logCRP (r = 0.409; P < 0.0001), and vWF (r = 206; P < 0.0001). Leptin was correlated with fibrinogen (r = 0.219, P < 0.0001), logCRP (r = 0.339, P < 0.0001), and vWF (r = 0.124, P = 0.002), but the statistical significance was lost after including BF in adjusted-correlation and multivariate analysis, suggesting that they are not regulated by leptin per se. In conclusion, the obesity-associated increase in the circulating concentrations of fibrinogen, CRP, and vWF is highly associated to BF and apparently not determined by leptin.
Influence of specific alternative diagnoses on the probability of pulmonary embolism
Authors: Testuz Ariane , Le Gal Grégoire , Righini Marc , Bounameaux Henri , Perrier Arnaud 
Published: May 2006

SummaryThe presence and likelihood of an alternative diagnosis to pulmonary embolism is an important variable of the Wells’ prediction rule for establishing clinical probability. We assessed whether evoking specific alternative diagnoses would reduce the probability of pulmonary embolism enough to forego further testing. We retrospectively studieda cohort of 965 consecutive patients admitted for suspicion of pulmonary embolism at three medical centers in Europe in whom the presence of an alternative diagnosis at least as likely as pulmonary embolism was recorded before diagnostic testing. We divided the patients into 15 categories of alternative diagnoses evoked. We then assessed the prevalence of pulmonary embolism in each diagnostic category and compared it to the prevalence of pulmonary embolism ina reference group (patients with no alternative diagnosis or a diagnosis less likely than pulmonary embolism). The prevalence of pulmonary embolism in the reference group was 48%. The presence of an alternative diagnosis as or more likely strongly reduced the probability of pulmonary embolism (OR 0.15, 95% CI: 0.1–0.2, p<0.01). In almost every diagnostic category, the prevalence of pulmonary embolism was much lower than in the reference group whith an odds ratio below or near 0. 2. Bronchopneumonia (OR 0.4, 95% CI 0.2 to 0.7) and cancer (OR 0.6, 95% CI 0. 3 to 1.5) reduced the likelihood of pulmonary embolism toa lower extent. Evoking an alternative diagnosis at least as likely as pulmonary embolism reduces the probability of the disease, but this effect is never large enough to allow ruling it out without further testing, especially when bronchopneumonia or cancer are the alternative diagnoses considered.
Pancha Kanya
Authors: Bhattacharya Pradip 
Published: May 2006

At times we come across traditional sayings that pose enigmas. Often, striving to resolve the puzzle turns into a quest, a search for meaning that, quite unexpectedly, throws light on problems facing us today. Such an enigmatic Sanskrit couplet exhorts invoking five females regularly to redeem us of failings, howsoever grievous. Ahalya draupadi kunti tara mandodari tatha/ Panchakanya smarenityam mahapataka nashinim// The choice of the five is itself intriguing, all being epic heroines: Ahalya, Tara and Mandodari from the Ramayana; Kunti and Draupadi from the Mahabharata. Even more so is the celebration of each as kanya, not as nari (woman) or sati (devoted to the husband). If kanya connotes ‘virgin’ (‘daughter’ makes no sense as several of them are not womb-born), the matter becomes more puzzling since each had intimate relationships with more than one man. In analysing what is known about them, we are surprised, for these heroines of ancient myth turn out to be, quite unexpectedly, guides for us in the twenty-first century.
Is tympanic membrane thermometry the best method for recording temperature in children?
Authors: Dew Paula L. 
Published: May 2006

Tympanic membrane thermometry has become increasingly popular for measuring temperature in children. The aim of this review is to ascertain the most appropriate, research-based thermometry method for use with children in acute healthcare settings. The following are considered: • Concerns regarding the accuracy of the tympanic membrane thermometer. • Whether comparison of the tympanic membrane thermometer with temperature measurement at other body sites is appropriate. • How choice of thermometer may be influenced by children's and nurses' preferences, technique, the age of the child, ear size and children with otitis media, perforated eardrums, cerumen (ear wax), ear pain or grommets in-situ. • Children's preferences and rectal thermometry in relation to children's rights, which have not been reviewed so far.
Socio-economic status, smoking during pregnancy and birth outcomes: an analysis of cross-sectional community studies in Liverpool (1993–2001)
Authors: Delpisheh Ali , Kelly Yvonne , Rizwan Shaheen , Brabin Bernard J. 
Published: May 2006

Objective: To assess the influence of socio-economic status on pregnancy outcomes in smoking mothers. Study design: Retrospective analysis. Methods: Parent-completed questionnaires addressing pregnancy smoking patterns and birth outcomes. Were distributed via children aged 5–11 years attending 10 primary schools in Merseyside. Data from three communitybased cross-sectional surveys undertaken in 1993, 1998 and 2001 were analysed. Townsend score was used as an indicator of household socioeconomic status. Results: 82.2 percent ( n = 3730) of respondents were classified as low (disadvantaged) socio-economic status. One-third of mothers smoked during pregnancy and this proportion was significantly higher among disadvantaged than advantaged categories (37.7% versus 14.6%; p < 0.001). The logistic regression analysis showed that only maternal smoking during preg-nancy was a significant risk factor for adverse birth outcomes when socioeconomic variables were controlled. Conclusion: Birth outcomes were worse in babies of smoking mothers during pregnancy independent of household's socio-economic status.
Opposing roles of blood myeloid and plasmacytoid dendritic cells in HIV-1 infection of T cells: transmission facilitation versus replication inhibition
Authors: Groot Fedde , van Capel Toni M. M. , Kapsenberg Martien L. , Berkhout Ben , de Jong Esther C. 
Published: May 2006

AbstractCD11c+ myeloid dendritic cells (MDCs) and CD11c– CD123+ plasmacytoid DCs (PDCs) have been identified as main human DC subsets. MDCs are professional antigen-presenting cells for T cells, and include Langerhans cells, dermal DCs, and interstitial DCs. They have been associated with HIV-1 capture and sexual transmission, whereas PDCs play an important role in the innate immune responses to different types of viruses, including HIV-1. To compare the influence of MDCs and PDCs on HIV-1 infection of T cells, we isolated donor-matched MDCs and PDCs from peripheral blood, activated them by adding different maturation-inducing compounds, and cocultured them with T cells and HIV-1. We found that MDCs enhance HIV-1 infection through capture of the virus and subsequent transmission to T cells, and that differently matured MDC subsets have different HIV-1 transmission efficiencies. These differences were not due to soluble factors, viral capture differences, or the expression of integrins ICAM-1, -2, -3, or LFA-1. In contrast, regardless of their state of maturation, PDCs inhibit HIV-1 replication in T cells through the secretion of IFNα and an additional, unidentified small molecule. This study shows that the 2 main types of DCs have opposing roles in HIV-1 infection of T cells.
Do CD8 effector cells need IL-7R expression to become resting memory cells?
Authors: Buentke Eva , Mathiot Anne , Tolaini Mauro , Di Santo James , Zamoyska Rose , Seddon Benedict 
Published: May 2006

AbstractThe role for IL-7R expression in the differentiation of effector T cells into resting memory remains controversial. Here, using a conditional IL-7R transgenic model, we were able to test directly whether CD8 effector T cells require IL-7R expression for their differentiation into resting memory cells. In the absence of IL-7R expression, effector cells transferred into “full” hosts underwent a protracted and unremitting contraction compared with IL-7R–expressing control cells and were unable to develop into long-term resting memory cells. Surprisingly, when the same effector cells were transferred into empty T-cell–deficient hosts, they could generate long-lived fully functional resting memory cells independently of IL-7R expression. Formation of these latter cells was found to be dependent on IL-15, because the same IL-7R–deficient effector cells were rapidly lost from IL-15–deficient hosts, having a half-life of less than 40 hours. Therefore, our data suggest that, under physiological conditions, both IL-7 and IL-15 synergize to promote the formation of memory cells directly by limiting the contraction of effectors that occurs following an immune response and that reexpression of IL-7R is a key checkpoint in the regulation of this process.
Teenage suicide cluster formation and contagion: implications for primary care
Authors: Johansson Lars , Lindqvist Per , Eriksson Anders 
Published: May 2006

AbstractBackgroundWe have previously studied unintentional as well as intentional injury deaths among teenagers living in the four northernmost counties, forming approximately 55% of Sweden with 908,000 inhabitants in 1991. During this work, we found what we suspected to be a suicide cluster among teenagers and we also suspected contagion since there were links between these cases. In this present study, we investigate the occurrence of suicide clustering among teenagers, analyze cluster definitions, and suggest preventive measures.MethodsA retrospective study of teenager suicides autopsied at the Department of Forensic Medicine in Umeå, Sweden, during 1981 through 2000. Police reports, autopsy protocols, and medical records were studied in all cases, and the police officers that conducted the investigation at the scene were interviewed in all cluster cases. Parents of the suicide victims of the first cluster were also interviewed. Two aggregations of teenager suicides were detected and evaluated as possible suicide clusters using the US Centers for Disease Control definition of a suicide cluster.ResultsTwo clusters including six teenagers were confirmed, and contagion was established within each cluster.ConclusionThe general practitioner is identified as a key person in the aftermath of a teenage suicide since the general practitioner often meet the family, friends of the deceased, and other acquaintances early in the process after a suicide. This makes the general practitioner suitable to initiate contacts with others involved in the well-being of the young, in order to prevent suicide cluster formation and para-suicidal activities.
Prevalence of amyloid deposition in long standing rheumatoid arthritis in Iranian patients by abdominal subcutaneous fat biopsy and assessment of clinical and laboratory characteristics
Authors: Alishiri G Hussein , Salimzadeh Ahmad , Owlia Mohammad Bagher , Forghanizadeh Jafar , Setarehshenas Roya , Shayanfar Nasrin 
Published: May 2006

Abstract

Background
The study was aimed at determining the prevalence of secondary amyloidosis in a group of Iranian patients with Rheumatoid Arthritis (RA), and the assessment of its correlation with the clinical and laboratory findings and data.

Method
A total number of 220 patients (167 female and 53 male) with a minimum five-year history of RA were selected. Congo red staining method was used for staining the specimens obtained by abdominal subcutaneous fat biopsy (ASFB) method. All of the specimens were examined for apple-green birefringence under polarized light microscope. Clinical and laboratory characteristics of the patients were assessed. Chi-square test and unpaired student's t-test were run for intergroup comparisons.

Results
Amyloid deposition test yielded positive results in 15 out of the 220 cases (6.8%) examined by the ASFB technique. Thirteen patients were found to have minimal amyloid deposits. Of all the clinically significant cases, 8 (53%) presented with proteinuria, and 7 cases (46.6%) had severe constipation.

Conclusion
The prevalence of fat amyloid deposits in Iranian patients with RA is low. In up to half of the study group the deposits were subclinical. Follow up studies are required to determine whether this subclinical amyloidosis can develop into full-blown clinically significant amyloidosis.