Liver stem cells and hepatocellular carcinoma.

Although the existence of cancer stem cells (CSCs) was first proposed over 40 years ago, only in the past decade have these cells been identified in hematological malignancies, and more recently in solid tumors that include liver, breast, prostate, brain, and colon. Constant proliferation of stem cells is a vital component in liver tissues. In these renewing tissues, mutations will most likely result in expansion of the altered stem cells, perpetuating and increasing the chances of additional mutations and tumor progression.

A report on the International Transglutaminase Autoantibody Workshop for Celiac Disease.

Objectives: Measurement of transglutaminase autoantibodies (TGAA) is considered to be the most efficient single serologic test for celiac disease (CD) by the American Gastroenterological Association Institute. We hypothesized that a large international collaborative effort toward improving and standardizing TGAA measurement is both feasible and necessary. The primary aim of this workshop is to compare TGAA assays among various research and clinical laboratories to examine assay concordance and improve (and eventually standardize) the TGAA assay.

Lymphocytic duodenosis and the spectrum of celiac disease.

Objectives: Celiac disease (CD) is a chronic inflammatory disease of the small bowel that is characterized by increased intraepithelial lymphocytes (IELs) and villous atrophy of the mucosa. It is unclear how often intraepithelial lymphocytosis in the absence of atrophy is a manifestation of gluten sensitive enteropathy. The objective of this study was to identify factors that discriminate patients with CD from those with lymphocytic duodenosis (LD, intraepithelial lymphocytosis without villous atrophy).

The role of HLA-DQ8 beta57 polymorphism in the anti-gluten T-cell response in coeliac disease.

Major histocompatibility complex (MHC) class II alleles HLA-DQ8 and the mouse homologue I-A(g7) lacking a canonical aspartic acid residue at position beta57 are associated with coeliac disease and type I diabetes. However, the role of this single polymorphism in disease initiation and progression remains poorly understood. The lack of Asp 57 creates a positively charged P9 pocket, which confers a preference for negatively charged peptides.

Clinical staging and survival in refractory celiac disease: a single center experience.

Background & Aims: Refractory celiac disease (RCD) occurs when both symptoms and intestinal damage persist or recur despite strict adherence to a gluten-free diet. In RCD, the immunophenotype of intraepithelial lymphocytes may be normal and polyclonal (RCD I) or abnormal and monoclonal (RCD II). The aim is to describe the clinical characteristics, treatment, and long-term outcome in a large single-center cohort of patients with RCD.

Fiberoptic endoscopic evaluation of swallowing.

Fiberoptic endoscopic evaluation of swallowing is a technique that allows for the assessment of pharyngeal dysphagia and the implementation of rehabilitation interventions with the goal of promoting safe and efficient swallowing. An overview of the equipment needed for the laryngoscopic evaluation, how to conduct the examination, what can be visualized endoscopically, diagnostic parameters, the implementation of therapeutic strategies, and suggestions for future research are discussed herein.

Prevalence of small intestine bacterial overgrowth diagnosed by quantitative culture of intestinal aspirate in celiac disease.

Background And Aim: A recent study using lactulose hydrogen-breath testing suggests that small intestine bacterial overgrowth (SIBO) is a common cause of nonresponsive celiac disease (CD). The prevalence of SIBO in CD diagnosed by quantitative culture of intestinal aspirate is unknown. The aim of this study is to evaluate the prevalence and significance of SIBO in CD based on the results of quantitative culture of intestinal aspirate.

Predictors of family risk for celiac disease: a population-based study.

Background & Aims: There is an elevated prevalence of celiac disease (CD) in family members (FMs) of CD patients, but most prior studies have been done on selected populations. Our aim was to determine the clinical, serologic, and genetic predictors of CD in FMs of a population-based cohort of index cases.

Methods: Index cases from southeast Minnesota provided contact information for their first-degree relatives.

Esophageal lichen planus.

Esophageal lichen planus is an underrecognized condition, with fewer than 50 cases reported to date. Unlike cutaneous lichen planus, esophageal lichen planus occurs almost exclusively in middle-aged or older women who also have oral involvement. It commonly involves the proximal esophagus and manifests as progressive dysphagia and odynophagia.

Celiac disease and autoimmunity in the gut and elsewhere.

This review focuses on the autoimmune connective tissue diseases, endocrine, and dermatologic conditions associated with celiac disease, as well as the related gut inflammatory disorders of refractory celiac disease, autoimmune enteropathy, collagenous enteritis, and collagenous colitis.

Copper deficiency in celiac disease.

Copper deficiency is an uncommonly reported complication of celiac disease that has not received much attention in recent years. Copper deficiency may result in anemia and thrombocytopenia and also irreversible myeloneuropathy if it is not detected and treated appropriately. The prevalence of copper deficiency in patients with celiac disease is unknown.

Celiac disease autoantibodies in severe autoimmune liver disease and the effect of liver transplantation.

Background/aims: Celiac disease (CD) is associated with primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. We investigated the following: (i) the prevalence of tissue transglutaminase antibodies (tTGAs) and endomysial antibodies (EMAs) in end-stage autoimmune liver disease (ESALD), (ii) the correlation among auto-antibodies and the human leucocyte antigen (HLA) haplotype, and (iii) the effect of liver transplantation on antibody kinetics.

Methods: Pretransplantation sera from 488 patients (310 with ESALD, and 178 with non-autoimmune disease) were tested for tTGAs.

Comparative usefulness of deamidated gliadin antibodies in the diagnosis of celiac disease.

Background & Aims: Serologic tests are used frequently in celiac disease diagnosis. Gliadin antibodies generally lack the accuracy required for proper diagnosis. We evaluated the value of deamidated gliadin antibody measurements in the diagnosis and follow-up evaluation of celiac disease and compared their potential usefulness with that of gliadin and tissue-transglutaminase antibodies.

Increased expression of the glioma-associated antigen ARF4L after loss of the tumor suppressor PTEN. Laboratory investigation.

Object: Despite recent advances in cancer immunotherapy, cellular mechanisms controlling expression of tumor-associated antigens are poorly understood. Mutations in cancer cells, such as loss of PTEN, may increase expression of tumor-associated antigens. The authors investigated the relationship between PTEN status and the expression of a glioma-associated antigen, adenosine diphosphate-ribosylation factor 4-like (ARF4L) protein.

Parental imprisonment: long-lasting effects on boys' internalizing problems through the life course.

Qualitative studies suggest that children react to parental imprisonment by developing internalizing as well as externalizing behaviors. However, no previous study has examined the effects of parental imprisonment on children's internalizing problems using standardized instruments, appropriate comparison groups, and long-term follow-up. Using prospective longitudinal data from the Cambridge Study in Delinquent Development, we compared boys separated because of parental imprisonment during their first 10 years of life with four control groups: boys who did not experience separation, boys separated because of hospitalization or death, boys separated for other reasons (usually parental disharmony), and boys whose parents were only imprisoned before the boys' births.

Mucosal atrophy in celiac disease: extent of involvement, correlation with clinical presentation, and response to treatment.

Background & Aims: Wireless capsule endoscopy provides an opportunity to study the macroscopic features in celiac disease by providing a magnified view of the intestinal mucosa. In this study, we evaluated the following: (1) the distribution of atrophy in untreated celiac disease, (2) the correlation between extent of changes and clinical manifestations, (3) the accuracy and interobserver agreement of wireless capsule endoscopy assessment, and (4) the effect of gluten withdrawal.

Methods: Thirty-eight consecutive patients with untreated biopsy-proven celiac disease underwent wireless capsule endoscopy.

The liver in celiac disease.

Celiac disease is a common (1% prevalence) chronic immune-mediated disorder of the small intestine induced by dietary wheat, barley, and rye. Several hepatic disorders have been described in association with celiac disease. Isolated hypertransaminasemia with nonspecific histologic changes in a liver biopsy is the commonest hepatic presentation of celiac disease.

Long-term fracture risk in patients with celiac disease: a population-based study in Olmsted County, Minnesota.

Celiac disease is associated with decreased bone density, but there are conflicting data regarding fracture risk. We determined the fracture incidence relative to matched controls in a population-based cohort with celiac disease before and after diagnosis. Olmsted County residents with celiac disease (n = 83) diagnosed between 1950 and 2002 were compared with 166 gender and age matched controls.

HLA DQ gene dosage and risk and severity of celiac disease.

Background & Aims: Celiac disease (CD) is a chronic inflammatory disorder of the small intestine that is strongly associated with certain HLA molecules encoded by DQA and DQB genes. The aim of this study was to examine the role of DQA and DQB alleles in determining the risk for and the age of onset and severity of CD in an American population.

Methods: High-resolution class 2 HLA genotyping was performed in a population-based sample (n = 84) of southeastern Minnesota residents with CD and a comparable control group (n = 102) to determine the contribution of DQA and DQB alleles to disease risk.

Innate immunomodulatory effects of cereal grains through induction of IL-10.

Background: Interactions between the gastrointestinal immune system and the luminal environment play critical roles in maintaining immune homeostasis and in diseases such as inflammatory bowel disease. Although immunomodulation by microbial factors has been studied extensively, little attention has been given to the potential immunomodulatory effects of ingested foods.

Objective: We characterized the effects of cereal grains on the immune response in human subjects and investigated the mechanism.

Heat shock protein 90alpha recruits FLIPS to the death-inducing signaling complex and contributes to TRAIL resistance in human glioma.

Heat shock protein 90 (HSP90) is a molecular chaperone that contributes to the proper folding and stability of target proteins. Because HSP90 has been suggested to interact with FLIP(S), the key regulator of tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in glioma cells, we examined the role HSP90 played in controlling TRAIL response. HSP90alpha was found to associate with FLIP(S) in resting cells in a manner dependent on the ATP-binding NH2-terminal domain of HSP90alpha.