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Biomedical subjects

E J Kuipers

Publications and source records attributed to E J Kuipers.

At least 19 recordsLinked to original sources
PubMed2003

Effect of frequent consumption of a Lactobacillus casei-containing milk drink in Helicobacter pylori-colonized subjects.

BACKGROUND: Several studies have reported inhibitory effects of lactic acid bacteria on bacterial pathogens. AIM: To test whether a drink containing Lactobacillus casei strain Shirota inhibits Helicobacter pylori growth. METHODS: The in vitro growth inhibition of H. pylori was studied when L. casei was added to plates previously inoculated with H. pylori reference strain NCTC 11637. In an intervention study, 14 H. pylori-positive subjects were given Yakult drink (10(8) colony-forming units/mL L. casei) thrice daily during meals for 3 weeks. Six untreated H. pylori-positive subjects served as controls. H. pylori bacterial loads were determined using the 13C-urea breath test, which was performed before and 3 weeks after the start of L. casei supplementation. RESULTS: In vitro, L. casei inhibits H. pylori growth. This effect was stronger with L. casei grown in milk solution than in DeMan-Rogosa-Sharpe medium. No growth inhibition was shown with medium inoculated with lactic acid, Escherichia coli strain DH5alpha or uninoculated medium. Filtration of L. casei culture before incubation with H. pylori completely abolished the inhibitory effect. Urease activity decreased in nine of the 14 (64%) subjects with L. casei supplementation and in two of the six (33%) controls (P = 0.22). CONCLUSIONS: Viable L. casei are required for H. pylori growth inhibition. This does not result from changes in lactic acid concentration. In addition, a slight, but non-significant, trend towards a suppressive effect of L. casei on H. pylori in vivo may exist.

Adult↗
PubMed2003

Increased apoptosis in gastric mucosa adjacent to intestinal metaplasia.

BACKGROUND: The biological processes involved in the development of gastric mucosal atrophy and intestinal metaplasia are still incompletely understood. Reports testing the hypothesis that apoptosis leads to atrophy have yielded conflicting results. The availability of new antibodies for the detection of apoptotic cells in tissue sections has facilitated the analysis of the role of apoptosis in the gastritis-atrophy-intestinal metaplasia sequence. METHODS: Archival material from 40 gastric resection specimens with normal mucosa (n = 5), chronic active gastritis (n = 17), or intestinal metaplasia (n = 18) was studied. Immunohistochemistry was performed using antibodies directed against cleaved cytokeratin 18 and active caspase 3. Slides were scored on a 0-3 scale for the presence of apoptotic cells. RESULTS: Normal gastric mucosa contained low numbers of apoptotic cells at the surface epithelium (mean score, 0.20). This number was significantly increased in cases with chronic gastritis (mean score, 1.06) and in those with intestinal metaplasia (mean score, 2.56). Within the intestinal metaplasia cases, 44 different foci of intestinal metaplasia were identified. In 39 of these 44 areas, concentrations of apoptotic cells were seen immediately adjacent to the foci of intestinal metaplasia, but not in the metaplastic epithelium itself. CONCLUSIONS: Apoptosis is uncommon in normal gastric mucosa. Chronic inflammation and intestinal metaplasia are associated with increased apoptosis, but occur mainly at the mucosal surface and not in the deeper layers. These findings do not support the concept that apoptosis underlies the loss of gastric glands and leads to atrophy, but the observed concentration of apoptotic epithelial cells adjacent to foci of intestinal metaplasia could be related to heterogeneity of epithelial damage, causing apoptosis, to which intestinal metaplasia is a response.

Apoptosis↗
PubMed2003

Comparative genomic hybridisation as a supportive tool in diagnostic pathology.

AIMS: Patients with multiple tumour localisations pose a particular problem to the pathologist when the traditional combination of clinical data, morphology, and immunohistochemistry does not provide conclusive evidence to differentiate between metastasis or second primary, or does not identify the primary location in cases of metastases and two primary tumours. Because this is crucial to decide on further treatment, molecular techniques are increasingly being used as ancillary tools. METHODS: The value of comparative genomic hybridisation (CGH) to differentiate between metastasis and second primary, or to identify the primary location in cases of metastases and two primary tumours was studied in seven patients. CGH is a cytogenetic technique that allows the analysis of genome wide amplifications, gains, and losses (deletions) in a tumour within a single experiment. The patterns of these chromosomal aberrations at the different tumour localisations were compared. RESULTS: In all seven cases, CGH patterns of gains and losses supported the differentiation between metastasis and second primary, or the identification of the primary location in cases of metastases and two primary tumours. CONCLUSION: The results illustrate the diagnostic value of CGH in patients with multiple tumours.

Adenocarcinoma↗
PubMed2002

[The malignant side of chronic inflammatory bowel disease].

Patients with chronic inflammatory bowel disease (IBD) have a higher risk of colorectal carcinoma, and present with this malignancy at a younger age than non-IBD individuals. In three patients, two men aged 20 and 36 years and one woman aged 34 years, colorectal cancer developed at a young age, following a long history of ulcerative colitis. Surveillance for colorectal cancer in IBD patients needs to be performed by regular colonoscopy with extensive biopsy sampling for the detection of dysplasia, regarded by many as predictive for colon carcinoma. Whenever a dysplasia-associated lesion or mass or a highgrade dysplasia is identified, there is a strong indication for colectomy. When low-grade dysplasia is found, the findings should be discussed with the patient and it should be decided whether the patient should resume surveillance or opt for colectomy.

Adenocarcinoma↗
PubMed2002

[From gene to disease; 'frame shift'-mutation in the CARD15-gene and Crohn's disease].

A pericentromeric region on chromosome 16 (IBD1 locus) has been linked with Crohn's disease (CD). Very recently, three genetic variants in the CARD15 gene within the IBD1 locus have been identified which were highly associated with CD. Carriage increases the relative risk of developing CD. One specific mutation (3020insC) leads to a stop codon and truncation of the C-terminal tandem leucine-rich repeats (LRR) of the CARD15 protein. Of all patients with Crohn's disease, 11-19% are heterozygous and 3-7% homozygous for this frameshift mutation. The CARD15 gene is expressed in monocytes. The LRR-domain is thought to be involved in the binding of bacterial lipopolysaccharide and subsequent activation of nuclear factor kappa-B (NF kappa B). NF kappa B plays a central role in the regulation of the expression of other genes involved in the inflammatory response. In vitro, embryonic kidney cells transfected with the CARD15 3020insC mutant showed a reduced activity of NF kappa B after exposure to lipopolysaccharide compared to cells transfected with the wild-type CARD15 gene. How the reduced response to lipopolysaccharide contributes to CD is not yet clear.

Carrier Proteins↗
PubMed2002

Helicobacter pylori does not mediate the formation of carcinogenic N-nitrosamines.

BACKGROUND: Both N-nitroso compounds and colonization with Helicobacter pylori represent known risk-factors for the development of gastric cancer. Endogenous formation of N-nitroso compounds is thought to occur predominantly in acidic environments such as the stomach. At neutral pH, bacteria can catalyze the formation of N-nitroso compounds. Based on experiments with a noncarcinogenic N-nitroso compound as end product, and using only a single H. pylori strain, it was recently reported that H. pylori only displays a low nitrosation capacity. As H. pylori is a highly diverse bacterial species, it is reasonable to question the generality of this finding. In this study, several genetically distinct H. pylori strains are tested for their capacity to form carcinogenic N-nitrosamines. MATERIALS AND METHODS: Bacteria were grown in the presence of 0-1000 microM morpholine and nitrite (in a 1 : 1 molar ratio), at pH 7, 5 and 3. RESULTS: Incubation of Neisseria cinerea (positive control) with 500 microM morpholine and 500 microM nitrite, resulted in a significant increase in formation of N-nitrosomorpholine, but there was no significant induction of N-nitrosomorpholine formation by any of the H. pylori strains, at any of the three pH conditions. CONCLUSION: H. pylori does not induce formation of the carcinogenic N-nitrosomorpholine in vitro. The previously reported weak nitrosation capacity of H. pylori is not sufficient to nitrosate the more difficulty nitrosatable morpholine. This probably also holds true for other secondary amines. These results imply that the increased incidence of gastric cancer formation that is associated with gastric colonization by H. pylori is unlikely to result from the direct induced formation of carcinogenic nitrosamines by H. pylori. However, this has to be further confirmed in in vivo studies.

Antigens, Bacterial↗
PubMed2002

Alterations in penicillin-binding protein 1A confer resistance to beta-lactam antibiotics in Helicobacter pylori.

Most Helicobacter pylori strains are susceptible to amoxicillin, an important component of combination therapies for H. pylori eradication. The isolation and initial characterization of the first reported stable amoxicillin-resistant clinical H. pylori isolate (the Hardenberg strain) have been published previously, but the underlying resistance mechanism was not described. Here we present evidence that the beta-lactam resistance of the Hardenberg strain results from a single amino acid substitution in HP0597, a penicillin-binding protein 1A (PBP1A) homolog of Escherichia coli. Replacement of the wild-type HP0597 (pbp1A) gene of the amoxicillin-sensitive (Amx(s)) H. pylori strain 1061 by the Hardenberg pbp1A gene resulted in a 100-fold increase in the MIC of amoxicillin. Sequence analysis of pbp1A of the Hardenberg strain, the Amx(s) H. pylori strain 1061, and four amoxicillin-resistant (Amx(r)) 1061 transformants revealed a few amino acid substitutions, of which only a single Ser(414)-->Arg substitution was involved in amoxicillin resistance. Although we cannot exclude that mutations in other genes are required for high-level amoxicillin resistance of the Hardenberg strain, this amino acid substitution in PBP1A resulted in an increased MIC of amoxicillin that was almost identical to that for the original Hardenberg strain.

Amoxicillin↗
PubMed2002

Polymorphisms of Helicobacter pylori HP0638 reflect geographic origin and correlate with cagA status.

Since the associations between Helicobacter pylori genotype and disease differ in Asia and the West, we investigated the correlation between HP0638, encoding an outer membrane protein, and potential markers of virulence (cagA, vacA, and iceA). For 109 strains from nine countries, the status of cagA, vacA, and iceA was determined by PCR and/or a line probe assay. We also studied 18 strains from 8 patients (parents and 6 daughters) from a Dutch family and paired strains collected on average 8 years apart from 11 patients. When the HP0638 signal sequences were amplified by PCR and DNA sequence determinations were performed, 89 (96%) of 93 cagA-positive strains had HP0638 in frame, versus none (0%) of 16 cagA-negative strains (P < 0.001). Among strains in which HP0638 was in frame, a six-CT dinucleotide repeat pattern was dominant in Western countries (23 of 33 strains [70%]), while a pattern of three CT repeats with another CT after four T's (3 + 1-CT-repeat pattern) was dominant in East Asia (31 of 46 strains [67%]); however, specific CT repeat patterns did not correlate with clinical outcome. HP0638 phylogenetic trees also showed geographic characters. The HP0638 frame status and CT dinucleotide repeat patterns were identical for 9 of 11 pairs of strains obtained on average 8 years apart from individuals and the 15 strains obtained from the mother and all six daughters. Thus, HP0638 frame status and cagA status are strongly correlated. The CT dinucleotide repeat pattern in the putative HP0638 signal sequence has geographic characters and appears stable in particular patients and families over a period of years. Analysis of HP0638 CT polymorphisms may serve as a new typing system to discriminate H. pylori isolates for epidemiological purposes.

Adult↗
PubMed2001

The role of Helicobacter pylori virulence factors in interleukin production by monocytic cells.

Helicobacter pylori infection results in chronic gastritis, which is initiated by the release of cytokines like interleukin (IL)-12 and IL-8 from mononuclear cells, and IL-8 from gastric epithelial cells. The severity of gastritis is influenced both by host factors and by bacterial factors such as the Cag proteins and the vacuolating cytotoxin VacA. Amounts of IL-12 and IL-8 produced by monocytic THP-1 cells differed considerably between the eight H. pylori isolates tested, but in contrast to H. pylori-induced IL-8 production by gastric epithelial cells, did not correlate to the Cag and VacA types of the strains. Apparently, in addition to Cag and VacA, other bacterial factors determine the extent in which H. pylori induced IL production in monocytes.

Antigens, Bacterial↗
PubMed2001

The dynamics of gastritis.

The dynamics of gastritis remain a topic of intense investigation. The results of these investigations have increased our knowledge concerning the development of preneoplastic lesions and cancer of the stomach and given us insight with regard to the interactions among bacterial colonization, chronic inflammation, and carcinogenesis in other organs. The past year has presented us with further data showing that the progression of chronic gastritis to gland loss and gastric cancer is related to the severity of inflammation, which is influenced by the characteristics of the bacterial strain, host genetics, and hypochlorhydria. In contrast, Helicobacter pylori eradication leads to a rapid disappearance of neutrophils in the gastric mucosa. Chronic inflammation with mononuclear cells also improves upon eradication, but at a much slower rate, usually not leading to normalization within the first year after therapy. Whether H. pylori eradication can thus prevent new development of atrophy and metaplasia as well, or lead to regression of pre-existing lesions, has been the topic of many studies by now. Unfortunately, most of these studies have suffered from their case design, limited sample size, and short follow-up. Therefore, the conflict in outcome of these case studies comes as no surprise. The few prospective, randomized, controlled studies, however, strongly confirm that H. pylori eradication leads to healing of gastritis, which can at least halt further development of atrophy and metaplasia. Whether these lesions can truly regress remains to be proven.

Gastritis↗
PubMed2001

Identification of environmental stress-regulated genes in Helicobacter pylori by a lacZ reporter gene fusion system.

BACKGROUND: Helicobacter pylori persists in the human stomach for decades. This requires an efficient adaptation of H. pylori to the gastric niche and involves the regulation of bacterial genes in response to environmental stress. Efficient molecular tools to identify regulated H. pylori genes are scarce, therefore we developed a genomic lacZ reporter gene fusion system in H. pylori to screen for stress-regulated genes. MATERIALS AND METHODS: The integration vector pBW was constructed and used to generate random genomic lacZ fusions in H. pylori. Two-hundred-and-fifty H. pylori transformants were selected from this library, replica-plated and screened for differential lacZ expression after exposure to two environmental stress conditions: increased temperature (42 degrees C), and iron-limitation. RESULTS: From a library of H. pylori transformants with random genomic transcriptional lacZ fusions, two stress-regulated H. pylori loci were identified. The transcription of a gene of unknown function (designated hsp12) was increased by incubation at 42 degrees C. The transcription of a locus, consisting of the three fumarate reductase subunit genes (frdCAB) and the HP0190 gene from H. pylori strain 26695, was decreased under iron-limitation. CONCLUSIONS: This is the first time that a genomic transcriptional lacZ reporter gene H. pylori library has been used as a tool for the fast and efficient identification of environmental stress-regulated H. pylori genes.

Bacterial Proteins↗
PubMed2001

Helicobacter pylori testing in the primary care setting: which diagnostic test should be used?

AIM: To identify the most accurate and efficient test for diagnosing Helicobacter pylori infection in primary care patients. STUDY DESIGN: A whole blood test, an ELISA, and carbon13 urea breath test (CUBT) were evaluated in a primary care setting and validated against two different gold standards that used gastric biopsies. POPULATION: Primary care patients who had dyspeptic complaints lasting at least 2 weeks and were referred for endoscopy. OUTCOMES MEASURED: Positive and negative predictive values, sensitivity and specificity were determined for all three noninvasive H. pylori tests. RESULTS: Data from the three non-invasive H. pylori tests were available for 136 primary care dyspeptic patients referred for endoscopy. They were compared with data from the gold standards. The positive predictive value of the whole blood test was in the range 71-75%, the ELISA 83-86%, and the CUBT 88-92%, while the negative predictive values were in the ranges 72-77%, 96-100%, and 95-98%, respectively. The sensitivity of the whole blood test was in the range 36-42%, the ELISA 93-100%, and the CUBT 92-97%, while the specificities were in the ranges 92-93%, 90-91% and 93-95%, respectively. The positive predictive value of the ELISA dropped significantly at lower H. pylori infection rates. DISCUSSION: Both the ELISA and CUBT are effective in the primary care setting, while the whole blood tests produces inferior results. ELISA might, however, be less suitable for detecting H. pylori infection in a population with a low rate of infection.

Adult↗
PubMed2001

Advantages and disadvantages of population screening for cancer and surveillance of at-risk groups.

Despite improvements in diagnostic and therapeutic modalities, the prognosis of patients with gastrointestinal malignancies has remained poor. In essence, this poor outcome is related to the majority of patients presenting at an already advanced stage of disease at the time of diagnosis. Unfortunately, however, mass screening and surveillance programmes aimed at early detection and treatment in the population at large are in most countries considered to be cost-ineffective. Moreover, even with regard to established risk groups, there is considerable debate over whether current surveillance strategies are beneficial to these patients in terms of a reduction in cancer-related mortality. This chapter addresses various aspects of screening and surveillance. In the first part, general issues are discussed, whereas the second part focuses particularly on disease entities frequently encountered in gastrointestinal practice.

Adult↗
PubMed2001

Gastric mucosal morphological consequences of acid suppression: a balanced view.

In the chapter, an analysis of the literature on the relationship between Helicobacter pylori, the use of proton pump inhibitors and the development of atrophic gastritis is presented, and the difficulties of classifying gastritis and the new possibilities of quantifying chronic inflammation by morphometric analysis are discussed. The issue surrounding the necessity of eradicating H. pylori in H. pylori-positive patients has still not been solved. Most studies have now accepted that proton pump inhibitors indeed accelerate the onset of atrophic gastritis in H. pylori-positive patients, but evidence against such an association was published in one recent (Scandinavian) study; conclusions from this study have, however, been challenged by several groups. Some data are available on the efficacy of H. pylori eradication with regard to the prevention of atrophy. The limited significance of the development of parietal cell protrusions and fundic gland cysts is better understood, but much less is known of the development and long-term consequence of H. pylori-induced autoimmune gastritis. Finally, recent studies in H. pylori-positive patients indicate that treatment with proton pump inhibitors may promote bacterial N-nitrosation formation. These data taken together suggest that the eradication of H. pylori may be based not only on morphological arguments, but also on bacterial alterations in the gastric milieu.

Anti-Ulcer Agents↗
PubMed2001

Distinct chromosomal aberrations in Epstein-Barr virus-carrying gastric carcinomas tested by comparative genomic hybridization.

BACKGROUND & AIMS: Approximately 10% of gastric adenocarcinomas carry the human pathogenic Epstein-Barr virus (EBV). The role of EBV in the pathogenesis of these carcinomas remains to be established. METHODS: To obtain a comprehensive overview of chromosomal aberrations in EBV-carrying and EBV-negative gastric carcinomas we performed comparative genomic hybridization (CGH) on 44 gastric carcinomas, 10 EBV-positive, and 34 EBV-negative. Additionally, DNA flow cytometry was done. RESULTS: Loss of chromosome 4p (P < 0.001) and of 11p (P < 0.02) was exclusively restricted to EBV-carrying gastric carcinomas. In addition, loss of 18q (P < 0.02) was significantly more frequent in EBV-carrying gastric carcinomas. The latter involves loci, which have already been linked to gastric carcinogenesis such as the DCC and SMAD4 gene. In contrast, the losses on chromosome 4 and 11 do not yet harbor a gene related to gastric carcinogenesis. No significant correlation was found between DNA-ploidy and the EBV-status. A number of chromosomal aberrations were found at comparable frequencies in both groups, i.e., losses of chromosome 17, 12q, and loss of 1p. Interestingly, gains of 13q (10/34) and 3q (5/34) and loss of 1q (5/34) were solely observed in EBV-negative gastric carcinomas. CONCLUSIONS: These data indicate that EBV-carrying and EBV-negative gastric carcinomas have different pathogenetic pathways in which EBV might play a crucial role.

Adenocarcinoma↗