Biomedical subjects

Fiebo J W Ten Kate

Publications and source records attributed to Fiebo J W Ten Kate.

12 recordsLinked to original sources

PubMed2006

Prevention of experimental colitis by parenteral administration of a pathogen-derived immunomodulatory molecule.

BACKGROUND: Filamentous haemagglutinin (FHA) of Bordetella pertussis subverts host immune responses by inhibiting interleukin (IL)12 and enhancing IL10 production by macrophages and dendritic cells, and promoting the induction of regulatory T cells. HYPOTHESIS: Injection of FHA would ameliorate disease in a T cell-dependent model of colitis via the induction of anti-inflammatory cytokines and regulatory T cells. METHODS: Colitis was induced by injection of CD4CD45RB(high) naive T cells into severe combined immunodeficient (SCID) mice. Mice were treated with four subcutaneous injections of FHA or buffer alone. RESULTS: Parenteral injection of FHA stimulated IL10 and/or transforming growth factor beta production in local and mesenteric lymph nodes and Peyer's patches of mice 2-6 h after administration. Compared with phosphate-buffered saline-treated mice, FHA-treated SCID mice had significantly (p<0.01) less weight loss, lower colon weight, less colon shrinkage and reduced inflammatory lesions. The therapeutic effect of FHA was associated with enhanced IL10 and reduced type 1 and type 2 T helper cytokine production by spleen cells. Finally, FHA also attenuated the symptoms of colitis in SCID mice transferred with CD4CD45RB(high) T cells from IL10-deficient mice. CONCLUSIONS: Our finding shows that FHA suppresses type 1 T helper and pro-inflammatory cytokines, and ameliorates disease activity in a chronic T cell-dependent model of colitis, an effect that was not dependent on IL10 production by T cells, but was associated with induction of anti-inflammatory cytokines in vivo. Having already been used as a pertussis vaccine component in children, FHA is a promising candidate for clinical testing in patients with Crohn's disease.

Adhesins, Bacterial↗

PubMed2006

Management of spontaneous haemorrhage and rupture of hepatocellular adenomas. A single centre experience.

BACKGROUND: Hepatocellular adenomas (HCA) may present with spontaneous haemorrhage and rupture. The aim of this study was to assess management in 22 patients treated for haemorrhage and/or rupture of HCA. PATIENTS AND METHODS: Between May 1990 and July 2005, 22 female patients were diagnosed with acute haemorrhage and/or rupture of lesions highly suspicious of HCA. Preoperative imaging diagnostics and pathologic specimens were reviewed. RESULTS: Twelve haemodynamically stable and four unstable patients could be treated conservatively. One patient underwent acute partial liver resection, whereas four patients underwent laparotomy with initial packing of the liver. In one patient, selective embolisation of the left hepatic artery was performed. Fifteen patients eventually underwent resection after a mean time of 8 months after initial treatment. Six patients did not undergo resection and showed no complications or rebleeding after a mean follow-up of 24.6 months. Only in seven patients, histopathological examination showed HCA, and in one patient, HCA with focal nodular hyperplasia. CONCLUSION: HCA with haemorrhage and/or rupture does not necessarily require immediate liver resection. Conservative treatment is justified in stable patients. In case of an instable patient with or without hemoperitoneum, laparotomy with packing or selective embolisation can stop the bleeding.

Adenoma, Liver Cell↗

PubMed2005

Agreement between endoscopic and histological gastric atrophy scores.

BACKGROUND: This study was conducted to investigate the strength of agreement between the endoscopic atrophic border (EAB) and the histological score for atrophy. METHODS: A series of 298 dyspeptic Japanese patients underwent upper endoscopy. The grade of gastric atrophy was estimated according to the EAB. Antral and corpus biopsy specimens were taken and were evaluated semiquantitatively according to the updated Sydney classification system, including the score for atrophy. The StatExact software package was used to calculate the weighted kappa statistics. RESULTS: The strength of agreement between the endoscopic atrophy score (EAB) and the histological atrophy score was good, with a weighted kappa value of 0.51 (95% confidence interval, 0.44-0.59). CONCLUSIONS: The strength of agreement between the endoscopic and histological atrophy scores is not worse than the interobserver histological agreement between two pathologists. It is worthwhile to carry out further research on the use of the EAB to identify and score gastric atrophy.

Aged↗

PubMed2005

Endoscopic video autofluorescence imaging may improve the detection of early neoplasia in patients with Barrett's esophagus.

BACKGROUND: The aim of this study was to investigate the feasibility of detecting high-grade dysplasia (HGD) and early cancer (EC) in Barrett's esophagus (BE) with a prototype video autofluorescence endoscope. METHODS: Sixty patients with BE were evaluated with a prototype, high-resolution videoendoscope that has separate charge-coupled devices for white light endoscopy (WLE) and autofluorescence imaging (AFI). Nondysplastic BE appears green on AFI, whereas potentially neoplastic areas appear blue/violet. The BE was first screened with WLE for visible abnormalities and then was examined by AFI to detect additional lesions. Lesions that raised a suspicion of neoplasia and control areas that were normal on AFI were sampled for histopathologic assessment. Finally, random 4-quadrant biopsy specimens were obtained at 2-cm intervals. RESULTS: A diagnosis of HGD/EC was made in 22 patients; one patient had no visible abnormality, and 21 had endoscopically detectable areas with HGD/EC. In 6 of the latter 21 patients, the HGD/EC was detected with AFI alone; in another patient, HGD/EC was detected with AFI and random biopsies. In 14 patients, HGD/EC was detected with both WLE and AFI; in 3 of these 14 patients, additional lesions containing HGD/EC were detected by AFI alone. CONCLUSIONS: The results of this study suggest that video AFI may improve the detection of HGD/EC in patients with BE.

Aged↗

PubMed2005

A randomized crossover study comparing light-induced fluorescence endoscopy with standard videoendoscopy for the detection of early neoplasia in Barrett's esophagus.

BACKGROUND: Light-induced fluorescence endoscopy (LIFE) may improve the detection of high-grade dysplasia (HGD) and early stage cancer (EC) in Barrett's esophagus (BE). The aim of this study was to compare LIFE with standard endoscopy (SE) in a randomized crossover study. METHODS: Fifty patients with BE underwent SE and LIFE in a randomized sequence (4 to 6-week interval between procedures). The two procedures were performed by two different endoscopists who were blinded to the findings of the other examination. Targeted biopsy specimens were taken from detected lesions, followed by random biopsy specimens with a 2-cm interval, 4-quadrant protocol. Biopsy specimens were routinely evaluated and subsequently reviewed by a single, blinded expert GI pathologist. RESULTS: Targeted biopsy specimens had a sensitivity for the diagnosis of HGD/EC of 62% (8/13) for both techniques. The overall sensitivity (all biopsy specimens) was 85% for SE and 69% for LIFE (p = 0.69). All targeted biopsy specimens had a positive predictive value (PPV) for HGD/EC of 41% for SE and 28% for LIFE (p = 0.40); autofluorescence-targeted biopsy specimens had a PPV of 13%. False-positive lesions had a significantly higher rate of acute inflammation than random biopsy specimens. CONCLUSIONS: In this study, LIFE did not improve the detection of HGD or EC in patients with BE compared with SE.

Barrett Esophagus↗

PubMed2005

Endoscopic treatment of high-grade dysplasia and early stage cancer in Barrett's esophagus.

BACKGROUND: The aim of this study was to prospectively evaluate endoscopic resection (ER) combined with photodynamic therapy (PDT) for the treatment of selected patients with early neoplasia in Barrett's esophagus. METHODS: Patients with Barrett's esophagus and neoplastic lesions <2 cm in diameter and no sign of submucosal infiltration, positive lymph nodes, or distant metastasis underwent diagnostic ER (cap technique). Patients with a T1sm tumor in the resection specimen were referred for surgery; those with a T1m or a less invasive tumor underwent additional endoscopic therapy (ER, PDT, and/or argon plasma coagulation [APC]), or they were followed. PDT was performed with 5-aminolevulinic acid and a light dose of 100 J/cm 2 at lambda = 632 nm. RESULTS: Thirty-three patients underwent diagnostic ER. Endoscopic treatment was not performed in 5 patients, who underwent surgery (4 T1sm; 1, patient preference). Five patients were immediately entered into a follow-up protocol, and 23 received additional endoscopic treatment (13 additional ER, 19 PDT, 3 APC). Endoscopic treatment was successful in 26/28 patients; no severe complication was observed. During follow-up (median 19 months, range 13-24 months), 5/26 patients had a recurrence of high-grade dysplasia: all were successfully re-treated with ER. At the end of follow-up, 26/33 originally enrolled patients (79%) and 26/28 endoscopically treated patients (93%) were in local remission. CONCLUSIONS: Endoscopic therapy is safe and effective for selected patients with early stage neoplasia in Barrett's esophagus.

Aged↗

PubMed2005

Geographic pathology of Helicobacter pylori gastritis.

BACKGROUND AND AIM: Helicobacter pylori is etiologically associated with gastritis and gastric cancer. There are significant geographical differences between the clinical manifestation of H. pylori infections. The aim of this study was to compare gastric mucosal histology in relation to age among H. pylori-infected patients from different geographical areas using the same grading system. The prevalence of atrophy and intestinal metaplasia were also compared with the respective gastric cancer incidence in the different countries. METHODS: A total of 1906 patients infected with H. pylori from seven countries were evaluated. Entry criteria included H. pylori positive cases with antral and corpus biopsies between the ages of 18 and 75 years. The minimum number of cases required from a country was 100. Hematoxylin-eosin stained biopsies from antrum and corpus were scored semiquantitatively using the parameters suggested by the Sydney Classification System. Statistical evaluation was performed using Kruskal-Wallis test and Spearman's rank correlation test. RESULTS: The severity of gastric atrophy varied among the different groups with the highest scores being present in Japan. The lowest scores were found in four European countries and in Thailand. The scores for intestinal metaplasia were low in general except for Xi-an, Japan, and Shanghai. For all the countries, the presence of atrophy in the antrum correlated well (r = 0.891) with the incidence of gastric cancer. CONCLUSION: Using a standardized grading system in a large study of H. pylori-related geographic pathology, we found major differences in the overall prevalence and severity of H. pylori gastritis in relation to age. These differences mirrored the respective incidences of gastric cancer in those geographical areas.

Adolescent↗

PubMed2004

In vivo evaluation of 111In-labeled T-lymphocyte homing in experimental colitis.

UNLABELLED: Blockade of lymphocyte recruitment to the intestinal mucosa is considered a useful therapy for inflammatory bowel disease (IBD) and anti-alpha4 antibodies have clinical benefit in patients with active Crohn's disease. The aim of this study was to evaluate a scintigraphic technique to assess lymphocyte homing to the colon in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced experimental colitis (TNBS colitis) in vivo. METHODS: TNBS-sensitized and nonsensitized murine total lymphocytes or CD4+ lymphocytes were radiolabeled with 111In-oxinate. Cells were injected into control mice (n = 5) or mice with TNBS colitis (n = 5). Specific abdominal radioactive uptake was determined by SPECT using a dedicated pinhole system 48 h after cell transfer. Radioactive colon uptake was correlated with histology and colon weight as parameters of inflammation. RESULTS: The radioactive colon uptake was most evident in mice with TNBS colitis that received sensitized lymphocytes (uptake ratio [mean +/- SEM], 0.51 +/- 0.03 vs. 0.22 +/- 0.04; P = 0.004). The sensitized 111In-labeled lymphocytes exacerbated colitis compared with nonsensitized lymphocytes. The colon uptake correlated well with both colon weight and histologic score (R2 = 0.836 and 0.933, respectively). The use of purified 111In labeled CD4+ lymphocytes resulted in a similar scintigraphic pattern. Administration of an anti-alpha4 antibody decreased radioactivity colon uptake of the (111)In-labeled cells compared with the control antibody in mice with TNBS colitis (uptake ratio, 0.72 +/- 0.14 to 0.33 +/- 0.03; P = 0.012). CONCLUSION: Animal pinhole SPECT can be applied for temporal and spatial analysis of the lymphocyte homing process in experimental colitis. This technique makes possible the in vivo evaluation of therapeutic efficacy of new drugs that interfere with lymphocyte migration. Moreover, colon uptake of radioactivity can be used as a parameter of disease activity in experimental colitis.

Animals↗

PubMed2002

Prevention of colitis by interleukin 10-transduced T lymphocytes in the SCID mice transfer model.

BACKGROUND & AIMS: Regulatory CD4(+) cells secreting the anti-inflammatory cytokine interleukin (IL)-10 play a key role in maintaining the immune balance in the intestinal mucosa. In this study we engineered primary CD4(+) cells to express IL-10 and investigated the efficacy of this approach in offering protection against experimental colitis. METHODS: Spleen-derived CD4(+) cells were transduced by using a retroviral vector to simultaneously express IL-10 and green fluorescent protein (GFP). The therapeutic benefit of CD4(+) cells transduced with IL-10 GFP was studied in experimental colitis, induced by transfer of CD45RB(high) CD4(+) cells to severe combined immunodeficient mice, and in acute trinitrobenzene sulfonic acid (TNBS)-induced colitis. RESULTS: Transferred engineered GFP fluorescent cells were detected for at least 15 weeks in peripheral blood, spleens, colon, and lymph nodes draining the intestine of recipient SCID mice. IL-10-GFP CD4(+) cells prevented CD45RB(high)-induced transfer colitis effectively, whereas no effect was observed after transfer of nontransduced CD4(+) cells. IL-10-GFP CD45RB(high) CD4(+) cells lost the capacity to induce colitis. By contrast, no therapeutic benefit was observed in TNBS-induced colitis. CONCLUSIONS: Primary murine CD4(+) cells that were engineered to express IL-10 by retroviral transduction act as regulatory cells in CD45RB(high)-induced transfer colitis. This approach may induce long-term maintenance of mucosal immune homeostasis in Crohn's disease.

Animals↗

PubMed2002

Interleukin-1 receptor type I gene-deficient bile duct-ligated mice are partially protected against endotoxin.

Cholestatic liver injury is associated with an increased susceptibility toward endotoxin-induced toxicity. To determine the role of interleukin 1 (IL-1) herein, extrahepatic cholestasis was induced by bile duct ligation (bdl) in IL-1 receptor type I gene-deficient (IL-1R(-/-)) mice, which are unresponsive to IL-1alpha and IL-1beta, and normal IL-1R(+/+) mice. Bdl elicited increases in hepatic IL-1alpha and IL-1beta messenger RNA (mRNA) and protein. Hepatocellular injury at 2 weeks after bdl was similar in IL-1R(-/-) and IL-1R(+/+) mice as shown by clinical chemistry and histopathology. Administration of endotoxin to cholestatic mice at 2 weeks after bdl was associated with enhanced cytokine release, more severe liver damage, and occurrence of death when compared with sham-operated mice. Endotoxin effects in sham-operated IL-1R(-/-) and IL-1R(+/+) mice were largely similar, but cholestatic IL-1R(-/-) mice were better protected against toxic effects of endotoxin, as reflected by lowered cytokine release, less profound liver injury, and reduced mortality. These data indicate that IL-1alpha and IL-1beta are produced in the liver after bdl, but that these cytokines do not play a significant role in cholestatic liver damage; however, endogenous IL-1 activity is an important denominator of enhanced endotoxin sensitivity that is observed during cholestasis induced by bdl.

Animals↗

PubMed2002

Endogenous interferon gamma protects against cholestatic liver injury in mice.

Cholestatic patients suffer from high perioperative morbidity and mortality, but the pathophysiology is still unknown. Interferon gamma (IFN-gamma) may play a role during cholestasis. Therefore, bile duct ligation (BDL) was induced in IFN-gamma alpha-chain receptor-deficient (IFN-gammaR(1)-/-) and wild-type (IFN-gammaR(1)+/+) mice. BDL elicited increased IFN-gamma messenger RNA and protein levels in the liver. One week after BDL, IFN-gammaR(1)+/+ mice showed less severe jaundice and liver injury than IFN-gammaR(1)-/- mice, as reflected by lower bilirubin and liver enzyme levels. In accordance, livers of IFN-gammaR(1)+/+ mice displayed smaller areas of necrosis by two-thirds than IFN-gammaR(1)-/- mice on histopathologic examination (P <.05), whereas mitotic activity and proliferating cell nuclear antigen (PCNA) labeling index was more than twice as high in IFN-gammaR(1)+/+ mice (P <.05). Livers of IFN-gammaR(1)+/+ mice displayed higher rates of apoptosis as indicated by DNA fragmentation rate, the number of apoptotic bodies, and poly ADP-ribose polymerase (PARP) immunostaining. BDL was not associated with lethality in IFN-gammaR(1)+/+ mice; IFN-gammaR(1)-/- mice, however, died from 10 days onward and survival after 2 weeks was 62% (10 of 16). In conclusion, these data suggest that IFN-gamma protects against liver injury during extrahepatic cholestasis by stimulation of apoptosis and subsequent proliferation of hepatocytes, leading to elegant removal of damaged hepatocytes, thus preventing necrosis and concomitant inflammatory responses.

Alanine Transaminase↗

PubMed2002

A survey of infectious agents as risk factors for primary sclerosing cholangitis: are Chlamydia species involved?

OBJECTIVES: The aetiology of primary sclerosing cholangitis (PSC) is unknown, and the role of micro-organisms has been studied only to a limited extent. We tested the hypothesis that past or persisting infection with common viruses or atypical bacteria might play a role in genetically susceptible hosts. DESIGN: Case-control study. METHODS: Serological screening for antibodies against 22 viruses as well as Chlamydia spp. and Mycoplasma pneumoniae was carried out in 41 well-established PSC patients. All 5110 sera tested in 1997 for these micro-organisms at our laboratory served as a background reference group. Subsequently, Chlamydia anti-lipopolysaccharide (LPS) antibodies were determined by enzyme-linked immunosorbent assay (ELISA) in the PSC group and in three race-matched control groups (inflammatory bowel disease (IBD) group, n = 35; non-IBD patients group, n = 39; healthy blood donor group, n = 40). Subtyping in Chlamydia trachomatis and C. pneumoniae serotypes by specific anti-major outer membrane protein (MOMP) assays was carried out in the four groups. Immunohistochemical staining using specific markers for chlamydiae was carried out on liver biopsies of 14 PSC patients. RESULTS: There was a markedly elevated seroprevalence of Chlamydia-LPS antibodies compared with the 1997 reference group. The odds ratios (ORs) for the presence of immunoglobulin G, immunoglobulin M and immunoglobulin A antibodies for the PSC patients versus the control group were 2.4 (95% confidence interval (CI) 1.1 to 5.4), 1.9 (95% CI 0.9 to 4.0) and 6.7 (95% CI 3.0 to 17.0), respectively. All other micro-organisms tested showed normal antibody profiles that did not differ from the 1997 reference group. The seroprevalence of Chlamydia-anti-LPS antibodies was elevated markedly in the PSC patients compared with the IBD, non-IBD and blood donor groups. The outcomes in the C. trachomatis and C. pneumoniae anti-MOMP assays did not correlate with the anti-LPS-positive PSC sera. The actual presence of Chlamydia bodies in liver tissue could not be demonstrated. CONCLUSION: Our findings suggest an association between PSC and (previous) infection with Chlamydia.

Adult↗