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Biomedical subjects

G Faller

Publications and source records attributed to G Faller.

At least 19 recordsLinked to original sources

[Solitary fibrous tumor in the tongue: case report and review of the literature].

Solitary fibrous tumors (SFT) are rare, mostly fibroblastic tumors usually situated in the pleura. Extrapleural manifestations have been described. However, the oral cavity is an uncommon localisation of this tumor. We report the very unusual case of an SFT affecting the tongue that could be removed completely because of its clear delineation. Intraoperative incisional biopsies were used to exclude malignancy. For definitive classification of the tumor, additional histopathologic examinations had to be carried out. Because SFT exhibit malignant behavior only in exceptional cases and their recurrence after complete removal has never been encountered, surgery can focus on the preservation of undisturbed function of the tongue.

Fibroma↗

Long-term acid suppression by omeprazole in gastro-oesophageal reflux disease patients does not lead to anti-gastric autoantibody production.

BACKGROUND: Helicobacter pylori-associated atrophy of the gastric corpus is associated with the presence of anti-canalicular autoantibodies. Also, long-term profound acid suppression in H. pylori-infected subjects may cause atrophic corpus gastritis. AIM: To investigate whether long-term acid suppression by omeprazole leads to antigastric autoantibodies. METHODS: Fifty patients, of which 34 H. pylori-positive on entry of the study, were treated with omeprazole (20-40 mg once daily) for reflux oesophagitis, and were evaluated for anti-gastric autoantibody responses by immunohistochemistry before and after treatment. H. pylori was not eradicated and patients were followed for an average of 6.6 years (range 3-14.1 years). In addition to immunohistochemistry, anti-H(+), K(+)-ATPase reactivity was assessed by Western blot in paired sera of 41 patients (26 H. pylori-positive and 15 uninfected) and results are critically evaluated. RESULTS: In immunohistochemistry, all patients were negative for anti-canalicular autoantibodies when omeprazole therapy started, except for two patients with corpus-predominant gastritis in the presence of H. pylori. One patient, who was H. pylori-negative, newly developed an anti-canalicular antibody response during therapy. CONCLUSIONS: Our results indicate that, as compared with non-infected patients, long-term profound acid suppression therapy in H. pylori-infected gastro-oesophageal reflux disease patients does not increase or accelerate gastric autoimmunity.

Adult↗

Demographics and presenting clinical features of childhood systemic lupus erythematosus.

OBJECTIVES: To review the presentation and characteristics of children with systemic lupus erythematosus (SLE). METHODS: The records of children with sufficient American College of Rheumatology (ACR) criteria for SLE treated by the renal units of the Johannesburg and Chris Hani Baragwanath hospitals, and the arthritis clinic of the Johannesburg Hospital between January 1974 and March 2000 were reviewed. The clinical presentation, age distribution and race were examined. RESULTS: A total of 36 children met the criteria. There were 26 girls and 10 boys, with a mean age of 11.5 and 10.2 years respectively. The male-to-female ratio was 1:2.6 overall, with a ratio of 1:1.2 under 10 years and 1:4 over 10 years. There were 15 white, 2 Indian and 5 coloured patients. The 14 black patients all presented after 1986. Rashes were found to be the commonest clinical feature present at the time of diagnosis, followed by polyarthritis and renal pathology. Constitutional symptoms were common, as were generalised lymphadenopathy and hepatosplenomegaly, while neurological, pulmonary and cardiac signs and symptoms were less common. Renal disease was present in 58% of patients on presentation. CONCLUSION: There is a diverse array of presenting features in childhood SLE. There has been increased recognition of the disease in young black South Africans since 1986.

Adolescent↗

High molecular weight polysaccharides from black currant seeds inhibit adhesion of Helicobacter pylori to human gastric mucosa.

Several crude and purified polysaccharides from black currant seeds (Ribes nigrum L.) have been isolated, analysed and examined on their effects against Helicobacter pylori in in situ adhesion studies on sections of human gastric mucosa. After pre-treatment of Helicobacter pylori with 0.01 to 0.1 % solutions of the isolated raw polysaccharide (RPS), the epithelial binding of the bacteria was considerably reduced in a concentration-dependent manner, as compared with a non-treated control suspension. Preincubation of the mucosal sections with 0.1 % solutions did not result in a reduced binding of non-treated bacteria. An anion-exchange fraction of RPS eluted with 0.1 M phosphate buffer exhibited a comparable, concentration-dependent reduction of adhesion, whereas the water-eluted fraction was ineffective at the respective concentrations. Both subfractions consisted of similar 1,3-linked galactans, decorated with side chains possessing 1,4-galacturonic acid, galactose and arabinose residues. Molecular weight profiling by GPC revealed that the antiadhesive activity of the buffer eluate correlated with high molecular weight components ranging from about 1000 Da to 340 kDa, whereas the ones of the inactive water eluate had molecular weights of about 100 and 25 kDa, respectively. None of the active fractions revealed inhibitory effects on bacterial growth in vitro. We conclude that acidic, high molecular weight galactans are responsible for the antiadhesive qualities of black currant seed extracts and that these polymers are able to block Helicobacter surface receptors, thus inhibiting their interaction with specific binding factors located on human gastric epithelia.

Bacterial Adhesion↗

Histopathological diagnosis of Barrett's mucosa and associated neoplasias: results of a consensus conference of the Working Group for Gastroenterological Pathology of the German Society for Pathology on 22 September 2001 in Erlangen.

There are a number of difficulties regarding the diagnosis of Barrett's mucosa and the varying grades of neoplasia that may be associated with it. It was, therefore, the aim of a consensus conference of the Working Group for Gastroenterological Pathology within the German Society of Pathology to achieve standardisation regarding the following issues: definition and diagnostic criteria for Barrett's mucosa and its discrimination from intestinal metaplasia of the cardia, diagnostic criteria for intraepithelial neoplasia, number of biopsies necessary to establish the diagnosis, significance of additional immunohistochemical and/or molecular methods as well as importance of a second opinion in the diagnosis of intraepithelial neoplasia.

Barrett Esophagus↗

[Histopathological diagnosis of Barrett's mucosa and associated neoplasias. Results of a consensus conference of the Working Group for "Gastroenterological Pathology of the German Society for Pathology" on 22 September 2001].

There are a number of difficulties regarding the diagnosis of Barrett's mucosa and the varying grades of neoplasia that may be associated with it. It was therefore the aim of a consensus conference of the "Working Group for Gastroenterological Pathology within the German Society of Pathology" to achieve standardization regarding the following issues: definition and diagnostic criteria for Barrett's mucosa and its discrimination from intestinal metaplasia of the cardia, diagnostic criteria for intraepithelial neoplasia, number of biopsies necessary to establish the diagnosis, significance of additional immunohistochemical and/or molecular biological methods as well as importance of a second opinion in the diagnosis of intraepithelial neoplasia.

Barrett Esophagus↗

Late pulmonary metastasis in uterine PEComa.

Perivascular epithelioid cell tumours (PEComas) other than angiomyolipoma, clear cell "sugar" tumour of the lung, and lymphangioleiomyomatosis are very rare mesenchymal tumours. The uterus seems to be the most prevalent site of involvement, but only 13 cases of uterine PEComa have been described. Three of these cases exhibited local aggressive behaviour and only one showed metastasis. Because of the extremely small number of cases, PEComas are considered tumours of uncertain malignant potential. This report describes a 68 year old woman, who presented with multiple pulmonary lesions seven years after the initial diagnosis of well differentiated endometrial stromal sarcoma. Histological and immunohistochemical analysis of the pulmonary lesions, in addition to re-evaluation of the primary uterine tumour, led to the final diagnosis of metastatic uterine PEComa. The findings indicate that any PEComa might have malignant potential. Spreading of this tumour to other organs might become evident even several years after primary manifestation.

Actins↗

Identification of a novel gene on chromosome 13 between BRCA-2 and RB-1.

METHODS AND RESULTS: By differential display we isolated a new cDNA-fragment, named C13, that is downregulated in malignant prostate tissues. Northern hybridization revealed the fragment to be part of 3.0 and 4.4 kb mRNAs. Fluorescence in situ hybridization, Southern blotting and radiation hybrid mapping demonstrated a chromosomal localization of C13 on 13q12-14 closest to the SHGC-34125 marker. In the 5% chromosomal environment of C13 we detected changes of the allelic status in 13 of 21 prostate cancers. A downregulation was detected at the mRNA level in patients with advanced carcinoma. The 3.0 kb full length cDNA clone encodes a protein with an open reading frame of 2,202 bp or 733 amino acids. The corresponding protein contains a putative nuclear localization signal, several glutamine clusters and an alpha-helix-rich domain. By in situ RNA hybridization we could demonstrate the mainly epithelial expression of the C13 mRNA in prostatic tissue. CONCLUSIONS: The localization of C13 between the tumor suppressor genes BRCA-2 and RB-1, the detected allelic imbalances, the downregulation of its mRNA in some prostatic cancer tissues, the epithelial expression and the described protein structure suggest that this gene encodes a protein that may have tumor or metastasis suppressing function in prostate tissue.

BRCA2 Protein↗

Lack of gastritis and of an adaptive immune response in interferon regulatory factor-1-deficient mice infected with Helicobacter pylori.

To study the role of T cell responses in Helicobacter pylori gastritis, C57BL/6 wild-type and interferon regulatory factor-1-deficient (IRF-1(-/-)) mice were infected with the mouse-adapted H. pylori Sydney strain. Mice lacking the transcription factor IRF-1 are defective in Th1 development and are therefore biased to mount a Th2-type response. After 4 months of infection, C57BL/6 mice developed severe gastritis and atrophy and mounted a Th1-type response towards H. pylori. The Th1 response was abrogated in IRF-1(-/-) mice. This defective Th1 response was associated with the total lack of gastritis and atrophy in IRF-1(-/-) mice despite severe colonization with H. pylori. In addition, IRF-1(-/-) mice did also not develop a Th2 reaction, since they failed to generate H. pylori-specific antibodies and to produce IL-4 in response to H. pylori antigens in vitro. Thus, the transcription factor IRF-1 is necessary for the development of gastritis and atrophy in H. pylori-infected wild-type mice, suggesting a role of Th1 cells in the pathogenesis of H. pylori-associated diseases.

Animals↗

[Helicobacter pylori and antigastric autoimmunity].

Recent studies report a significant association between Helicobacter pylori gastritis and autoimmune reaction. Antigastric autoantibodies are detectable in about 30% of H. pylori infected patients. Two major in situ binding sites have been found: first, at the luminal membrane of the foveolar epithelium in antrum and corpus mucosa and, second, at canalicular membranes within parietal cells in the corpus mucosa. The presence of latter type of autoantibodies is correlated with histological and clinical parameters of corpus mucosa atrophy. The gastric H+/K(+)-ATPase, which is already known as an autoantigen in classic autoimmune gastritis, also represents a major target in atrophic H. pylori gastritis. According to recent data molecular mimicry between H. pylori and the host does not play a pathogenic role in the formation these autoantibodies. In conclusion, antigastric autoimmunity represents a relevant host factor which contributes to the final outcome of H. pylori gastritis.

Autoantibodies↗

Association between infection with Helicobacter pylori and Chlamydia pneumoniae and risk of ischemic stroke subtypes: Results from a population-based case-control study.

BACKGROUND AND PURPOSE: Helicobacter pylori and Chlamydia pneumoniae have been associated epidemiologically and pathogenetically with coronary atherosclerosis. However, population-based data on chronic infection and stroke are lacking. Therefore, we investigated the association of both bacterial pathogens and ischemic stroke subtypes in a population-based case-control study. METHODS: Patients with first ischemic stroke in the population-based Erlangen Stroke Project were collected as cases. Neighborhood controls were drawn from the study population, matched for age, sex, and place of residence. IgG antibodies to H pylori were measured by enzyme immunoassay, and IgG antibodies to C pneumoniae were measured by microimmunofluorescence technique. Conditional logistic regression was used. Analyses were stratified for etiologic stroke subtypes according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. RESULTS: A total of 145 case and 260 control subjects were included. Chronic H pylori infection was associated with a higher risk of stroke caused by small-artery occlusion (adjusted odds ratio, 3.31; 95% CI, 1.15 to 9.56) and a lower risk of cardioembolic stroke (adjusted odds ratio, 0.21; 95% CI, 0.06 to 0.71). Overall, elevated H pylori as well as elevated C pneumoniae antibodies were not associated with ischemic stroke. CONCLUSIONS: Our population-based study does not provide evidence of any strong association between the immune response to C pneumoniae as a marker of prior infection and ischemic stroke. Further studies are required to reveal the role of chronic H pylori infection as an independent risk factor for the subgroup small-artery occlusion.

Aged↗

Role of antigastric autoantibodies in chronic Helicobacter pylori infection.

In recent studies a significant association between H. pylori infection and antigastric autoimmunity has been reported. Antigastric autoantibodies can be found in more than 30% of infected patients. Two distinct binding patterns of these autoantibodies have been described, first at the luminal membrane of the foveolar epithelium, and second at the canaliculi membranes of the parietal cells in the body mucosa. The latter type of autoantibodies correlates with histologic and clinical parameters of gastric mucosa atrophy. The gastric H,K-ATPase, which is known to be the autoimmune target in classical autoimmune gastritis, also represents a major autoantigen in atrophic H. pylori gastritis. Molecular mimicry between H. pylori and the host does not seem to be responsible for the generation of this type of autoreactivity. The development of antigastric autoantibodies may be a relevant host factor which contributes to the final clinical outcome of chronic H. pylori gastritis.

Autoantibodies↗

[Hypereosinophilia with myocardial involvement due to toxocariasis. Diagnosis of regional myocardial perfusion abnormalities by pulsed tissue Doppler echocardiography].

CASE REPORT: The case of a 57-year-old woman is reported who was admitted for peripheral hypereosinophilia. DIAGNOSIS: Detailed investigations revealed first of all a hypereosinophilic syndrome with infiltration of bone marrow and lung. The patient suffered more and more from angina pectoris with signs of heart failure. Coronary angiography was therefore carried out which showed normal coronary arteries. With suspicion of myocardial involvement endomyocardial biopsies were performed which revealed the presence of Löfflers endocarditis parietalis fibroplastica. Finally, serological studies for parasites disclosed a positive ELISA test for Toxocara, confirmed later to be rising. CONCLUSION: Myocardial involvement of hypereosinophilia, caused by Toxocara is not described until now. Further diagnostic by means of pulsed wave tissue Doppler echocardiography provided regional differentiation of a restrictive filling pattern which documented the importance of this new diagnostic tool in myocardial illness.

Animals↗

Significant increase in antigastric autoantibodies in a long-term follow-up study of H. pylori gastritis.

In 30% of H. pylori-infected patients a certain type of antigastric autoantibodies, reacting against canalicular structures within human parietal cells, is detectable. Furthermore, it has been shown that these autoantibodies are correlated with atrophy of the mucosa in the corpus. The aim of this study was to analyse the prevalence of these anticanalicular autoantibodies (ACAB) and their significance for development of gastric mucosa atrophy in a 12-year follow-up period. Gastric biopsy specimens from 62 persons in Saaremaa Island, Estonia, were collected in 1997 and assessed independently by two pathologists in accordance with the updated Sydney system. The sera of these persons were immunohistochemically screened for ACAB and for classic parietal cell antibodies (PCA). In addition, for 37 of the 62 persons, gastric biopsies and sera collected 12 years earlier (1985) were investigated in an analogous manner. ACAB increased significantly, from 8 out of 37 in 1985 to 17 out of 37 in 1997 (P=0.004; McNemar test). In 1997 a significant correlation existed between the presence of ACAB and corpus mucosa atrophy (19 out of 30 versus 10 out of 32 without atrophy; P=0.01; odds ratio (OR)=3.8, 95% CI 1.4-10.6). However, no correlation was found between ACAB and development of atrophy in the period from 1985 to 1997. All 37 persons were PCA negative in 1985, whereas in 1997, 2 turned out to be PCA positive. ACAB increased significantly with duration of H. pylori gastritis. The correlation between ACAB and presence of gastric corpus atrophy was confirmed. However, it is possible that ACAB are the consequence of and not a causative factor in gastric mucosa atrophy, insofar as the association of ACAB with progression of corpus atrophy was not significant.

Aged↗

Expression of nuclear beta-catenin and c-myc is correlated with tumor size but not with proliferative activity of colorectal adenomas.

Most colorectal cancers have loss-of-function mutations in the adenomatosis polyposis coli (APC) tumor suppressor gene. This leads to the accumulation of nuclear beta-catenin, which, together with the DNA-binding protein TCF-4, functions as a transcriptional activator. The recently defined target genes c-myc, cyclin D1, and matrilysin are responsible for tumor proliferation or malignant progression and explain the oncogenic potential of nuclear beta-catenin. To investigate its role in early colon carcinogenesis, we analyzed the expression of beta-catenin, its target gene c-myc, and the proliferative activity in 88 colorectal adenomas of varying size and grade of dysplasia. The results revealed i) the most significant correlation of nuclear beta-catenin and c-myc expression was not with the grade of dysplasia but with the size of the colon adenoma; ii) perfect correlation of nuclear beta-catenin and c-myc expression; iii) no significant correlation of adenoma size with the proliferative activity; and iv) no significant correlation of proliferative activity and the nuclear expression of beta-catenin and c-myc. These results imply that APC mutations have additional beta-catenin-independent functions; APC mutations alone are not sufficient for nuclear overexpression of beta-catenin; and nuclear beta-catenin has additional important functions for exceeding a threshold tumor size.

Adenoma↗

Lewis X structures in the O antigen side-chain promote adhesion of Helicobacter pylori to the gastric epithelium.

Helicobacter pylori NCTC11637 expresses a lipopolysaccharide (LPS) that comprises an O antigen side-chain with structural homology to the human blood group antigen Lewis X (Le(x)). The role of this molecule in adhesion of H. pylori to gastric epithelial cells was investigated. Mutants expressing truncated LPS structures were generated through insertional mutagenesis of rfbM and galE; genes encode GDP mannose pyrophosphorylase and galactose epimerase respectively. Compositional and structural analysis revealed that the galE mutant expressed a rough LPS that lacked an O antigen side-chain. In contrast, an O antigen side-chain was still synthesized by the rfbM mutant, but it lacked fucose and no longer reacted with anti-Le(x) monoclonal antibodies (Mabs). The ability of these mutants to bind to paraffin-embedded sections from the antrum region of a human stomach was assessed. Adhesion of the wild type was characterized by tropic binding to the apical surface of mucosal epithelial cells and cells lining gastric pits. In contrast, both the rfbM and galE mutants failed to demonstrate tropic binding and adhered to the tissue surface in a haphazard manner. These results indicate that LPS and, more specifically, Le(x) structures in the O antigen side-chain play an important role in targeting H. pylori to specific cell lineages within the gastric mucosa. The role of Le(x) in this interaction was confirmed by the tropic binding of synthetic Le(x), conjugated to latex beads, to gastric tissue. The observed pattern of adhesion was indistinguishable from that of wild-type H. pylori.

Bacterial Adhesion↗