Association of autoimmune type atrophic corpus gastritis with Helicobacter pylori infection

AIM:To study the association between Helicobacter pylori(H.pylori)infection and autoimmune type atrophic gastritis. METHODS:Twenty-three patients with different grades of atrophic gastritis were analysed using enzyme immunoassay-based serology,immunoblot-based serology,and histology to reveal a past or a present H.pylori infection.In addition,serum markers for gastric atrophy(pepsinogenⅠ,pepsinogenⅠ/Ⅱand gastrin)and autoimmunity[parietal cell antibodies(PCA), and intrinsic factor(IF),antibodies]were determined. RESULTS:Of the 14 patients with severe gastricatrophy,as demonstrated by histology and serum markers,and no evidence for an ongoing H.pylori infection,eight showed H.pylori antibodies by immunoblotting.All eight had elevated PCA and 4/8 also had IF antibodies.Of the six immunoblot-negative patients with severe corpus atrophy,PCA and IF antibodies were detected in four.Among the patients with low to moderate grade atrophic gastritis(all except one with an ongoing H.pylori infection),serum markers for gastric atrophy and autoimmunity were seldom detected.However,one H.pylori negative patient with mild atrophic gastritis had PCA and IF antibodies suggestive of a pre-atrophic autoimmune gastritis. CONCLUSION:Signs of H.pylori infection in autoimmune gastritis,and positive autoimmune serum markers in H.pylori gastritis suggest an etiological role for H.pylori in autoimmune gastritis.

Immunogenetic characteristics of patients with autoimmune gastritis

AIM:To explore whether predisposition to autoimmune gastritis (AIG) is found in human leukocyte antigen (HLA), cytokine or killer cell immunoglobulin-like receptor (KIR) gene variations.METHODS: Twelve Finnish patients with autoimmunetype severe atrophy of the gastric corpus were included. The patients' serum was analyzed for pepsinogen-interleukin (IL)-1 gene cluster, IL-2, IL-4, IL-6, IL-10, IL-12, interferon γ, transforming growth factor β, and tumor necrosis factor α. Variation in KIR genes was also explored. The results were compared with prevalence of the polymorphisms in Finnish or European populations.RESULTS: All patients had pepsinogen-CONCLUSION: As explored with modern DNA-based methods, HLA-DRB1*04 and DQB1*03 alleles, but not HLA-B8-DRB1*03, may predispose to AIG.

High-sensitivity C-reactive protein in paediatric inflammatory bowel disease

AIM:To study whether high-sensitivity C-reactive protein(hs-CRP) measurement can aid the assessment of disease activity and glucocorticoid treatment in paediatric inflammatory bowel disease(IBD).METHODS:CRP levels were measured in 39 children with IBD undergoing colonoscopy [median age 12.8 years,Crohn's disease(CD) n=20],in 22 other children with IBD followed for acute response to glucocorticoids,and in 33 paediatric non-IBD patients.When standard CRP level was below detection limit(<5mg/L),hs-CRP was analyzed.RESULTS:Sixty-four percent(25/39) of the children with IBD undergoing colonoscopy displayed undetectable(<5mg/L) standard CRP levels.Of these,the hs-CRP measurement could not differentiate between active(median,0.2 mg/L,range,0.007-1.37,n=17) or quiescent(0.1 mg/L,0.01-1.89,n=8,P=NS) disease.Patients with ileocolonic CD had higher CRP levels(14mg/L,0.06-45,n=13) than patients with no ileal involvement(0.18 mg/L,0.01-9,n=7,P<0.01) or ulcerative colitis(UC)(0.13 mg/L,0.007-23,P<0.05).In children with active IBD treated with systemic glucocorticoids,the standard CRP was undetectable in 59% of the patients.The hs-CRP levels did not differ between patients that responded to steroid therapy and in non-responders.CONCLUSION:The measurement of hs-CRP did not prove useful in the assessment of disease activity or glucocorticoid treatment in paediatric IBD patients that had undetectable standard CRP.

Myofibroblastic cell activation and neovascularization predict native liver survival and development of esophageal varices in biliary atresia

AIM: To study the relation between collagen 1, &#x003b1;-smooth muscle actin (&#x003b1;-SMA) and CD34 expression and the most essential portoenterostomy (PE) outcomes.

Gene mutations in stool from gastric and colorectal neoplasia patients by next-generation sequencing

AIM To study cancer hotspot mutations by next-generation sequencing(NGS) in stool DNA from patients with different gastrointestinal tract(GIT) neoplasms. METHODS Stool samples were collected from 87 Finnish patients diagnosed with various gastric and colorectal neoplasms, including benign tumors, and from 14 healthy controls. DNA was isolated from stools by usingthe PSP~? Spin Stool DNA Plus Kit. For each sample, 20 ng of DNA was used to construct sequencing libraries using the Ion AmpliS eq Cancer Hotspot Panel v2 or Ion AmpliS eq Colon and Lung Cancer panel v2. Sequencing was performed on Ion PGM. Torrent Suite Software v.5.2.2 was used for variant calling and data analysis.RESULTS NGS was successful in assaying 72 GIT samples and 13 healthy controls, with success rates of the assay being78% for stomach neoplasia and 87% for colorectal tumors. In stool specimens from patients with gastric neoplasia, five hotspot mutations were found in APC,CDKN2 A and EGFR genes, in addition to seven novel mutations. From colorectal patients, 20 mutations were detected in AKT1, APC, ERBB2, FBXW7, KIT, KRAS,NRAS, SMARCB1, SMO, STK11 and TP53. Healthy controls did not exhibit any hotspot mutations, except for two novel ones. APC and TP53 were the most frequently mutated genes in colorectal neoplasms, with five mutations, followed by KRAS with two mutations.APC was the most commonly mutated gene in stools of patients with premalignant/benign GIT lesions.CONCLUSION Our results show that in addition to colorectal neoplasms,mutations can also be assayed from stool specimens of patients with gastric neoplasms.

Stool antigen tests in the diagnosis of Helicobacter pylori infection before and after eradication therapy

Aim： To evaluate two enzyme immunoassay-based stool antigen tests, Premier Platinum HpSA and Amplified IDEIA HpStAR, and one rapid test, ImmunoCard SLAT! HpSA, in the primary diagnosis of Helicobacter pylon （H pylori） infection and after eradication therapy. METHODS： Altogether 1 574 adult subjects were screened with a whole-blood H pylori antibody test and positive results were confirmed with locally validated serology and ^13C-urea breath test. All 185 subjects, confirmed to be H pylori positive, and 97 H pylorinegative individuals, randomly selected from the screened study population and with negative results in serology and UBT, were enrolled. After eradication therapy the results of 182 subjects were assessed. RESULTS： At baseline, the sensitivity of HpSA and HpStARwas 91.9% and 96.2%, respectively, and specificity was 95.9% for both tests. ImmunoCard had sensitivity of 93.0% but specificity of only 88.7%. After eradication therapy, HpSA and HpStAR had sensitivity of 81.3% and 100%, and specificity of 97.0% and 97.6%, respectively. ImmunoCard had sensitivity of 93.8% and specificity of 97.0%. HpSA, HpStAR, and ImmunoCard had PPV 77%, 80%, and 75%, and NPV 98%, 100%, and 99%, respectively. CONCLUSION： In primary diagnosis, the EIA-based tests performed well. After eradication therapy, negative results were highly accurate for all the three tests. HpStAR had the best overall performance.

Differential roles of EPS8 in carcinogenesis:Loss of protein expression in a subset of colorectal carcinoma and adenoma

AIM:To analyze the epidermal growth factor receptor pathway substrate 8(EPS8) expression status and role in colorectal carcinogenesis given that EPS8 has a conserved actin barbed-end capping function that is required for proper maturation in intestinal cells.METHODS:We studied 8 colon cancer cell lines and 58 colorectal tumors(19 adenomas and 39 carcinomas).We performed expression microarray analysis of colon cancer cell lines followed by loss of heterozygosity(LOH)analysis and immunohistochemistry for EPS8 expression in colon tumors.Subsequently,we performed mutation analysis by direct sequencing and methylation analysis by bisulfite sequencing and methylation-specific polymerase chain reaction assays.RESULTS:Expression microarray analysis of colon cancer cell lines showed overexpression of EPS8 transcript in all lines but RKO.Genome wide loss of heterozygosity(LOH) analysis of colon tumors,showed considerable LOH at the EPS8 gene locus.Immunohistochemically,EPS8 was constitutively expressed in normal colonic mucosa with a dot-like supranuclear localization with accentuation at the luminal surface supporting its proposed role in epithelial maturation.Nineteen colon tumors(4 adenoma,15 carcinoma) out of 51(37%) showed strikingly tumor specific EPS8 protein loss.Of the remaining tumors,5/51(2 adenoma,and 3 carcinoma,10%) showed marked overexpression,while 27/51 tumors(53%) showed retained expression.Mutation analysis revealed a missense mutation(c.794C>T,p.R265C) in exon 8 in RKO.The EPS8 promoter was also methylated in RKO,but there was no significant methylation in other cell lines or carcinoma specimens.CONCLUSION:The loss of EPS8 expression in colorectal adenomas and carcinomas suggests that down regulation of this gene contributes to the development of a subset of colorectal cancers,a finding which could have applications in diagnosis and treatment.

Matrix metalloproteinases in the restorative proctocolectomy pouch of pediatric ulcerative colitis

AIM:To investigate matrix metalloproteinases(MMPs) and their tissue inhibitors(TIMPs) in pouch mucosa of pediatric onset ulcerative colitis(UC).METHODS:In this cross-sectional study,28 patients with pediatric onset UC underwent ileal pouch biopsy 13 years(median) after proctocolectomy.Expression of MMPs-3,-7,-8,-9,-12 and-26 and TIMPs-1,-2 and-3 in samples was examined using immunohistochemichal methods,and another biopsy was used to evaluate the grade of histological inflammation.Two investigators independently graded the immunohistochemical specimens in a semiquantitative fashion,using a scale marking staining intensity as follows:0 = less than 20 positive cells;1 = 20-50 positive cells;2 = 50-200 positive cells;3 = over 20 positive cells.Fecal calprotectin and blood inflammatory markers [serum C-reactive protein(CRP) and erythrocyte sedimentation rate] were determined during a follow-up visit to examine correlations between these markers and the expression of MMPs and TIMPs.RESULTS:Of the 28 patients with pediatric onset UC,nine had not experienced pouchitis,whereas thirteen reported a single episode,and six had recurrent pouchitis(≥ 4 episodes).At the time of the study,six patients required metronidazole.In all of the others,the most recent episode of pouchitis had occurred over one month earlier,and none were on antibiotics.Only four samples depicted no sign of inflammation,and these were all from patients who had not had pouchitis.Two samples were too small to determine the grade of inflammation,but both had suffered pouchitis,the other recurrent.No sample depicted signs of colonic metaplasia.Most pouch samples showed expression of epithelial(e) and stromal(s) MMP-3(e,n = 22;s,n = 20),MMP-7(e,n = 28;s,n = 27),MMP-12(e,n = 20;s,n =24),TIMP-2(e,n = 23;s,n = 23) and MMP-3(e,n = 23;s,n = 28) but MMP-8(e,n = 0;s,n = 1),MMP-9(e,n = 0;s,n = 9) and MMP-26(e,n = 0;s,n = 3) and TIMP-1(n = 0,both) were lacking.In samples with low grade of inflammatory activity,the epithelial MMP-3 and MMP-7 expression was increased(r =-0.614 and r =-0.472,respectively,P < 0.05 in both).MMPs and TIMPs did not correlate with the markers of inflammation,fecal calprotectin,erythrocyte sedimentation rate,or CRP,with the exception of patients with low fecal calprotectin(< 100 μg/g) in whom a higher expression of epithelial MMP-7 was found no differences in MMPor TIMP-profiles were seen in patients with a history of pouchitis compared to ones with no such episodes.Anastomosis with either straight ileoanal anastomosis or ileoanal anastomosis with J-pouch did depict differences in MMP-or TIMP-expression.CONCLUSION:The expression of MMPs pediatric UC pouch in the long-term shares characteristics with inflammatory bowel disease,but inflammation cannot be classified as a reactivation of the disease.

Possible Correlation between INR and Serum Calcium

Experimental and clinical studies have shown that long term anticoagulation therapy with warfarin can induce vascular calcification which is preventable by vitamin K. Osteoporosis has been shown to be associated with vascular calcification. In the present study, we wanted to see, whether INR (International Normalized Ratio), a measure of prothrombin time, and serum calcium (corrected by albumin) correlate in laboratory data of 94 anticoagulation patients on warfarin therapy. When adjusted on age and sex, there was an inverse correlation between the two variables. Clinical relevance of this observation and explanation of lowered calcium levels in blood parallel to increase in INR-values remain to be studied further.

Do multiparous women need to work or exercise extra hard to control gestational diabetes?

In the current issue of the Journal of Sport and Health Science,Wang et al.^(1)describe their prospective study,where they analyzed whether or not multiple pregnancies would influence glycemia and the glycemic response to physical exercise in gestational diabetes mellitus(GDM).2 Multiparous women are known to be at a higher risk for GDM than primiparas.GDM carries an increased risk for adverse perinatal outcomes,not only for the mothers but also for the newborn babies.Due to a contemporary environment that is conducive to a sedentary lifestyle and obesity,the incidence of GDM among pregnant women is increasing.

Discontinuation of Statin Treatment in Relation to Chronic Diseases and Laboratory Findings

Purpose: The aim was to study discontinuation of statin treatment, especially with respect to clinical characteristics and adverse effect measured by clinical laboratory tests indicating muscle damage (plasma creatine kinase, CK) and liver AEs (plasma alanine aminotransferase, ALAT). Methods: The initial study population included 60,488 individuals who had purchased first time statin prescription in Helsinki-Uusimaa region between 01-01-2007 and 31-12-2009. The follow-up started when first statin prescription was purchased and ended 31-12-2009 or death, which ever occurred first. From this population 54,172 individuals were defined to eligible to study population of this study. Clinical laboratory measurements were obtained from Helsinki-Uusimaa University Hospital (HUSLAB) that which provides the laboratory tests for the Helsinki-Uusimaa region serving about a population of 1.5 million. Results: In this fairly large real-life study the occurrence of ALAT-AE and mild CK-elevations after initiation of first statin treatments were relatively low. Increasing age and the presence of co-morbidities increased the risk of these AEs. Further, the ALAT-AEs implied increased risk of discontinuation of treatment. Diabetic patients discontinued treatment more often than non-diabetics, whereas the presence of other chronic conditions implied higher persistence of statin treatment. Conclusions: It is essential that those who would benefit from statin therapy actually are treated and by far in most patients treatment seems to be safe and well tolerated. For those who cannot tolerate statins new therapeutic options are needed.

Physiology of gangliosides and the role of antiganglioside antibodies in human diseases

Gangliosides are structurally and functionally polymorphic sialic acid containing glycosphingolipids that are widely distributed in the human body.They play important roles in protecting us against immune attacks,yet they can become targets for autoimmunity and act as receptors for microbes,like the influenza viruses,and toxins,such as the cholera toxin.The expression patterns of gangliosides vary in different tissues,during different life periods,as well as in different animals.Antibodies against gangliosides(AGA)can target immune attack e.g.,against neuronal cells and neutralize their complement inhibitory activity.AGAs are important especially in acquired demyelinating immune-mediated neuropathies,like Guillain–Barrésyndrome(GBS)and its variant,the Miller–Fisher syndrome(MFS).They can emerge in response to different microbial agents and immunological insults.Thereby,they can be involved in a variety of diseases.In addition,antibodies against GM3 were found in the sera of patients vaccinated with Pandemrix®,who developed secondary narcolepsy,strongly supporting the autoimmune etiology of the disease.