Automated harvesting and 2-step purification of unclarified mammalian cell-culture broths containing antibodies.

Therapeutic monoclonal antibodies represent one of the fastest growing segments in the pharmaceutical market. The growth of the segment has necessitated development of new efficient and cost saving platforms for the preparation and analysis of early candidates for faster and better antibody selection and characterization. We report on a new integrated platform for automated harvesting of whole unclarified cell-culture broths, followed by in-line tandem affinity-capture, pH neutralization and size-exclusion chromatography of recombinant antibodies expressed transiently in mammalian human embryonic kidney 293T-cells at the 1-L scale.

Antimicrobial peptides in the duodenum at the acute and convalescent stages in patients with diarrhea due to Vibrio cholerae O1 or enterotoxigenic Escherichia coli infection.

Patients with acute watery diarrhea caused by Vibrio cholerae O1 or enterotoxigenic Escherichia coli (ETEC) were analyzed for innate immune factors produced by the epithelium during the disease process. Duodenal biopsies were obtained from study participants at the acute (day 2) and convalescent (day 21) stages of disease. Levels of α-defensin (HD-5 and -6), β-defensin (hBD-1-4), and cathelicidin (LL-37) mRNAs were determined by real-time qRT-PCR.

Health check-ups and family screening allow detection of hereditary hemochromatosis with less advanced liver fibrosis and survival comparable with the general population.

Objective: The information concerning the morbidity and mortality of hereditary hemochromatosis is based primarily on clinical cohorts of symptomatic patients. The major aim of this study was to analyze the long-term prognosis for Swedish patients with this condition, with respect to both clinical features and survival, in relation to the route by which the disease was detected.

Patients And Methods: 373 patients with hemochromatosis detected through routine health check-ups (n = 153), family screening (n = 44), symptoms of arthralgia (n = 23), investigation of other diseases/symptoms (n = 108) or signs of liver disease (n = 45) were monitored for a mean period of 11.

The relationship between the val158met catechol-O-methyltransferase (COMT) polymorphism and irritable bowel syndrome.

Background: The catechol-O-methyltransferase (COMT) enzyme has a key function in the degradation of catecholamines and a functional polymorphism is val158met. The val/val genotype results in a three to fourfold higher enzymatic activity compared with the met/met genotype, with the val/met genotype exhibiting intermediate activity. Since pain syndromes as well as anxiety and depression are associated to low and high COMT activity respectively and these conditions are all associated with irritable bowel syndrome (IBS) we wanted for the first time to explore the relationship between the polymorphism and IBS.

Characteristics and long-term outcome of patients with autoimmune hepatitis related to the initial treatment response.

Objectives: Autoimmune hepatitis (AIH) is a liver disease which, if untreated, may lead to liver cirrhosis and hepatic failure. Limited data exist regarding factors predicting the long-term outcome. The aims of this study were to investigate symptoms at presentation, prognostic features, management and treatment in relation to long-term outcome of AIH.

Transitions between variant forms of primary biliary cirrhosis during long-term follow-up.

Background: Conditions exhibiting features of two different autoimmune liver diseases are designated overlap syndromes. Variant forms display some, but not all, characteristics of a distinct autoimmune liver disease. We describe transitions over time between variant forms of PBC, i.

High prevalence of small duct primary sclerosing cholangitis among patients with overlapping autoimmune hepatitis and primary sclerosing cholangitis.

Background: Overlap syndrome is a term used for overlapping features of autoimmune hepatitis and primary sclerosing cholangitis or primary biliary cirrhosis and for autoimmune cholangitis. We describe a high prevalence of small duct primary sclerosing cholangitis among patients with overlapping autoimmune hepatitis and primary sclerosing cholangitis.

Methods: We sought to retrieve all patients with overlap syndrome between primary sclerosing cholangitis and autoimmune hepatitis in six university hospitals in Sweden.

Hepatic and extrahepatic malignancies in autoimmune hepatitis. A long-term follow-up in 473 Swedish patients.

Background/aims: Autoimmune Hepatitis (AIH) is a liver disease which may lead to liver cirrhosis. Cirrhosis is a well-known risk factor for hepatocellular cancer. Lymphoma is a disease, where immune modulating drugs as well as the autoimmune disease itself may contribute to the elevated risk.

Budd-Chiari syndrome in Sweden: epidemiology, clinical characteristics and survival - an 18-year experience.

Background: The exact incidence and prevalence of Budd-Chiari syndrome (BCS) is unknown in the general population. Published reports differ in terms of the clinical characteristics, effects of therapy and survival.

Aims: To investigate the epidemiology, clinical presentation and survival in patients with BCS.

Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis.

Background & Aims: The importance of genetic factors for the development of primary sclerosing cholangitis (PSC) is incompletely understood. This study assessed the risk of PSC and inflammatory bowel disease (IBD) among first-degree relatives of patients with PSC, compared with the first-degree relatives of a cohort without PSC.

Methods: Subjects from the national Swedish cohort of PSC patients (n = 678) were matched for date of birth, sex, and region to up to 10 subjects without a diagnosis of PSC (n = 6347).

Epidemiology and the initial presentation of autoimmune hepatitis in Sweden: a nationwide study.

Objective: Autoimmune hepatitis (AIH) is a chronic liver disease, which if untreated can lead to cirrhosis and hepatic failure. The aim of the study was to investigate the incidence, prevalence, diagnostic tradition and clinical initial presentation of AIH.

Material And Methods: Analyses were performed in 473 patients identified as having probable or definite AIH.

Diet in the aetiology of ulcerative colitis: a European prospective cohort study.

Background/aims: The causes of ulcerative colitis are unknown, although it is plausible that dietary factors are involved. Case-control studies of diet and ulcerative colitis are subject to recall biases. The aim of this study was to examine the prospective relationship between the intake of nutrients and the development of ulcerative colitis in a cohort study.

Gastrointestinal symptoms are associated with hypothalamic-pituitary-adrenal axis suppression in healthy individuals.

Objective: The brain-gut axis has been proposed to influence symptoms in irritable bowel syndrome (IBS). In animal studies corticotropin-releasing hormone (CRH) challenge has been associated with decreased upper gastrointestinal motility and increased colonic motility. The purpose of this study was to investigate the association between gastrointestinal symptoms and the effect of CRH on the hypothalamic-pituitary-adrenal (HPA) axis using a weight-adjusted low-dose dexamethasone test in a group of healthy individuals (n = 157).

Autoimmune hepatitis among fertile women: strategies during pregnancy and breastfeeding?

Objective: In published studies there is a lack of data about the risks, management and how women with autoimmune hepatitis (AIH) decide on and are advised about pregnancy. The aim of this study was to investigate how women with AIH consider pregnancies, are advised and pharmacologically treated, as well as the outcome.

Material And Methods: A questionnaire was mailed to 128 women with AIH diagnosed during their fertile period and data from the Swedish National Birth Register was also used for matched controls.

Beta-defensin production by human colonic plasma cells: a new look at plasma cells in ulcerative colitis.

Background: Previously, we showed that colonic epithelium of ulcerative colitis (UC) patients expresses increased levels of mRNA for 3 antimicrobial peptides, human beta-defensin 2 (hBD-2), hBD-3, and hBD-4 compared to controls.

Methods: Human colon mucosa was analyzed using double immunofluorescence staining, in situ hybridization, immunoelectron microscopy, and quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) with specific antibodies and probes in the respective assays.

Results: We demonstrate that lamina propria in colon from UC patients, Crohn's colitis patients, and controls contain cells that express hBD-2.

High-dose ursodeoxycholic acid in primary sclerosing cholangitis: a 5-year multicenter, randomized, controlled study.

Background & Aims: There is no medical treatment of proven benefit for primary sclerosing cholangitis. This study aimed at studying the effect of a higher dose of ursodeoxycholic acid than previously used on survival, symptoms, biochemistry, and quality of life in this disease.

Methods: A randomized placebo-controlled study was performed in tertiary and secondary gastroenterology units.

Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study.

Background & Aims: Despite treatment with corticosteroids, severe to moderately severe attacks of ulcerative colitis have a high colectomy rate. We intended to find a rescue therapy other than cyclosporin A, which imposes a high risk of side effects and cyclosporine-related mortality.

Methods: This was a randomized double-blind trial of infliximab or placebo in severe to moderately severe ulcerative colitis not responding to conventional treatment.

Reduced susceptibility to dextran sulphate sodium-induced colitis in the interleukin-2 heterozygous (IL-2) mouse.

Summary Mice homozygous for an inactivation of the interleukin-2 (IL-2) gene develop a T-cell dependent colitis. Heterozygous (IL-2+/-) mice are clinically healthy but have been shown to express reduced levels of IL-2 in the colon. Splenocytes from the IL-2+/- mice had a poorer proliferative response to polyclonal T-cell activation and these mice have reduced numbers of intestinal regulatory T cells (CD4+ CD25+ cells) when compared to wild type mice.