Antibody-mediated delivery of T-cell epitopes to antigen-presenting cells induce strong CD4 and CD8 T-cell responses.

Targeted delivery of antigen to antigen-presenting cells (APCs) enhances antigen presentation and thus, is a potent strategy for making more efficacious vaccines. This can be achieved by use of antibodies with specificity for endocytic surface molecules expressed on the APC. We aimed to compare two different antibody-antigen fusion modes in their ability to induce T-cell responses; first, exchange of immunoglobulin (Ig) constant domain loops with a T-cell epitope (Troybody), and second, fusion of T-cell epitope or whole antigen to the antibody C-terminus.

Observation of the onset of a blue jet into the stratosphere.

Blue jets are lightning-like, atmospheric electric discharges of several hundred millisecond duration that fan into cones as they propagate from the top of thunderclouds into the stratosphere. They are thought to initiate in an electric breakdown between the positively charged upper region of a cloud and a layer of negative charge at the cloud boundary and in the air above. The breakdown forms a leader that transitions into streamers when propagating upwards.

A terrestrial gamma-ray flash and ionospheric ultraviolet emissions powered by lightning.

Terrestrial gamma-ray flashes (TGFs) are transient gamma-ray emissions from thunderstorms, generated by electrons accelerated to relativistic energies in electric fields. Elves are ultraviolet and optical emissions excited in the lower ionosphere by electromagnetic waves radiated from lightning current pulses. We observed a TGF and an associated elve using the Atmosphere-Space Interactions Monitor on the International Space Station.

EPC/HPSG evidence-based guidelines for the management of pediatric pancreatitis.

Background: Pediatric pancreatitis is an underdiagnosed disease with variable etiology. In the past 10-15 years the incidence of pediatric pancreatitis has increased, it is now 3.6-13.

Exploring structure and interactions of the bacterial adaptor protein YjbH by crosslinking mass spectrometry.

Adaptor proteins assist proteases in degrading specific proteins under appropriate conditions. The adaptor protein YjbH promotes the degradation of an important global transcriptional regulator Spx, which controls the expression of hundreds of genes and operons in response to thiol-specific oxidative stress in Bacillus subtilis. Under normal growth conditions, the transcription factor is bound to the adaptor protein and therefore degraded by the AAA+ protease ClpXP.

Gastrointestinal quality-of-life after cholecystectomy: indication predicts gastrointestinal symptoms and abdominal pain.

Background: Despite the fact that cholecystectomy is a common surgical procedure, the impact on long-term gastrointestinal quality of life is not fully known.

Methods: All surgical procedures for gallstone disease performed at Mora County Hospital, Sweden, between 2 January 2002 and 2 January 2005, were registered on a standard database form. In 2007, all patients under the age of 80 years at follow-up were requested to fill in a form containing the Gastrointestinal Quality-of-Life Index (GIQLI) questionnaire and a number of additional questions.

Monitoring dominant strictures in primary sclerosing cholangitis with brush cytology and FDG-PET.

Background & Aims: Despite a high risk of cholangiocellular adenocarcinoma (CCA) it is unclear how surveillance of patients with primary sclerosing cholangitis (PSC) should be performed.

Methods: We evaluated a follow-up algorithm of brush cytology and positron emission tomography/computed tomography with [(18)F] fluorodeoxyglucose ([(18)F]FDG-PET/CT), measured as maximum standardized uptake values, normalized to the liver background (SUVmax/liver) at 180 min, in PSC patients with dominant bile duct strictures.

Results: Brush cytology with high grade dysplasia (HGD) was detected in 12/70 patients (17%), yielding a diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 56%, 89%, 75%, and 88%, respectively.

Biliary microflora in patients undergoing cholecystectomy.

Background: The management of acute cholecystitis requires a sound knowledge of the biliary microflora.

Methods: Bile samples were taken for culture according to a standard routine during all cholecystectomies performed from April 2007 to February 2009 in the Department of Surgery at Enköping Hospital. The use of antibiotics within the 3-mo period before surgery, indication for surgery, prophylactic antibiotics, and post-operative complications were recorded prospectively.

Effectiveness of antibiotic prophylaxis in cholecystectomy: a prospective population-based study of 1171 cholecystectomies.

Background: The aim of this study was to assess the benefit from antibiotic prophylaxis (AP) during cholecystectomy in a population-based cohort study.

Methods: All cholecystectomies performed in Uppsala County, 2003-2005, were registered prospectively according to a standardized protocol. High-risk procedures (HP) were defined as operations for acute cholecystitis and procedures including exploration of the common bile duct.

CD40/APC-specific antibodies with three T-cell epitopes loaded in the constant domains induce CD4+ T-cell responses.

CD4+ T lymphocytes play a central role in the orchestration and maintenance of the adaptive immune response. Targeting of antigen to antigen presenting cells (APCs) increases peptide loading of major histocompatibility complex (MHC) class II molecules and CD4+ T-cell activation. APCs have been targeted by APC-specific recombinant antibodies (rAbs) with single T-cell epitopes integrated in the constant region of the heavy chain (C(H)).

Registration of health-related quality of life in a cohort of patients undergoing cholecystectomy.

Background. Assessment of gallstone surgery's impact on quality of life (QoL) requires a reliable instrument with sufficient responsiveness. The instrument should also enable estimation of each individual's expected condition in an unaffected state.

Are liver function tests, pancreatitis and cholecystitis predictors of common bile duct stones? Results of a prospective, population-based, cohort study of 1171 patients undergoing cholecystectomy.

Objective: The purpose of this study was to explore the accuracy of elevated liver function values, age, gender, pancreatitis and cholecystitis as predictors of common bile duct stones (CBDS).

Methods: All patients operated on for gallstone disease over a period of 3 years in a Swedish county of 302,564 citizens were registered prospectively. Intraoperative cholangiography (IOC) was used to detect CBDS.

Associations between fungal species and water-damaged building materials.

Fungal growth in damp or water-damaged buildings worldwide is an increasing problem, which has adverse effects on both the occupants and the buildings. Air sampling alone in moldy buildings does not reveal the full diversity of fungal species growing on building materials. One aim of this study was to estimate the qualitative and quantitative diversity of fungi growing on damp or water-damaged building materials.

Psychiatric caseness is a marker of major depressive episode in general practice.

Objective: Screening for a major depressive episode (MDE) in high-risk groups of patients within the primary care setting has been suggested by several Central Health Organizations. The objective of this study was to investigate whether patients rated as "psychiatric cases" by their general practitioner (GP) were likely to suffer from MDE and therefore qualified for systematic diagnostic screening.

Design: Cross-sectional survey of primary care patients assessed through depression screening questionnaires and GP consultations.

Validation of Gastrointestinal Quality of Life Index in Swedish for assessing the impact of gallstones on health-related quality of life.

Objective: The aim of the present study was to validate a Swedish translation of the Gastrointestinal Quality of Life Index (GIQLI) questionnaire in patients with gallstone disease.

Methods: Sensitivity to change, internal consistency, and test-retest stability were tested in 187 consecutive patients who underwent planned cholecystectomy. Construct validity was assessed by comparing the GIQLI score with the bodily pain scale of SF-36 and four single-item questions in a separate group of 104 patients.

Primary patency of percutaneously inserted self-expanding metallic stents in patients with malignant biliary obstruction.

Background: Effective bile duct drainage is crucial to the health-related quality of life of patients with jaundice caused by obstruction of the bile duct by inoperable malignant tumours.

Methods: All patients who were treated at Uppsala University Hospital, Sweden with percutaneous stenting between 2000 and 2005 were identified retrospectively. Data on the location of the obstruction and type of stent used, date and cause of death and date of stent failure were abstracted from the patients' notes.

Structural requirements for the interaction of human IgM and IgA with the human Fcalpha/mu receptor.

Here we unravel the structural features of human IgM and IgA that govern their interaction with the human Fcalpha/mu receptor (hFcalpha/muR). Ligand polymerization status was crucial for the interaction, because hFcalpha/muR binding did not occur with monomeric Ab of either class. hFcalpha/muR bound IgM with an affinity in the nanomolar range, whereas the affinity for dimeric IgA (dIgA) was tenfold lower.

Low recurrence rate after laparoscopic (TEP) and open (Lichtenstein) inguinal hernia repair: a randomized, multicenter trial with 5-year follow-up.

Objectives: To compare a laparoscopic (totally extraperitoneal patch (TEP)) and an open technique (Lichtenstein) for inguinal hernia repair regarding recurrence rate and possible risk factors for recurrence.

Summary Background Data: Laparoscopic hernia repair has been introduced as an alternative to open repair. Short-term follow-up suggests benefits for those patients operated with a laparoscopic approach compared with open techniques; ie, less postoperative pain and a shorter convalescence period.

Processing of an antigenic sequence from IgG constant domains for presentation by MHC class II.

Targeting of T cell epitopes to APC enhances T cell responses. We used an APC-specific Ab (anti-IgD) and substituted either of 18 loops connecting beta strands in human IgG constant H (C(H)) domains with a characterized T cell peptide epitope. All Ab-epitope fusion molecules were secreted from producing cells except IgG-loop 2(BC)C(H)1, and comparing levels, a hierarchy appeared with fusions involving C(H)2 > or = C(H)1 > C(H)3.

Identification of residues in the Cmu4 domain of polymeric IgM essential for interaction with Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1).

The binding of nonspecific human IgM to the surface of infected erythrocytes is important in rosetting, a major virulence factor in the pathogenesis of severe malaria due to Plasmodium falciparum, and IgM binding has also been implicated in placental malaria. Herein we have identified the IgM-binding parasite ligand from a virulent P. falciparum strain as PfEMP1 (TM284var1 variant), and localized the region within this PfEMP1 variant that binds IgM (DBL4beta domain).

TPS, CA 19-9, VEGF-A, and CEA as diagnostic and prognostic factors in patients with mass lesions in the pancreatic head.

Introduction: Although numerous tumour markers are available for periampullary tumours, including pancreatic cancer, their specificity and sensitivity have been questioned.

Materials And Methods: To assess the diagnostic and prognostic values of tissue polypeptide specific antigen (TPS), carbohydrate antigen 19-9 (CA 19-9), vascular endothelial growth factor (VEGF-A), and carcinoembryonic antigen (CEA) we took serum samples in 56 patients with mass lesions in the pancreatic head. Among these patients, further investigations revealed pancreatic cancer in 20 patients, other malignant diseases in 12 and benign conditions in 24.

How reliable is intraoperative cholangiography as a method for detecting common bile duct stones? : A prospective population-based study on 1171 patients.

Background: Although intraoperative cholangiography (IOC) is a widely used method for detecting common bile duct stones (CBDS), its accuracy has not been fully evaluated in large nonselected patient samples. The purpose of this study was to assess the sensitivity, specificity and predictive value of dynamic IOC regarding its ability to diagnose CBDS in a population-based setting, and to assess the morbidity associated with the investigation.

Methods: All patients operated on for gallstone disease between 2003 and 2005 in the county of Uppsala in Sweden, a county with a population of 302,000 in December 2004, were registered prospectively.

Recombinant antibodies for delivery of antigen: a single loop between beta-strands in the constant region can accommodate long, complex and tandem T cell epitopes.

Recombinant antibodies are increasingly used for efficient delivery of T cell epitopes to antigen-presenting cells (APCs), both for vaccination purposes and for immune modulation. We have previously shown that recombinant antibodies can accommodate single T cell epitopes inserted into loops between beta-strands in constant (C) domains. Such recombinant antibodies have in addition been equipped with variable regions that target APCs for increased delivery of C region T cell epitopes.