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M Stolte

Publications and source records attributed to M Stolte.

At least 73 records · Page 4Linked to original sources
PubMed2001

Down-regulation of Akt/PKB in senescent cardiac fibroblasts impairs PDGF-induced cell proliferation.

OBJECTIVE: Cardiovascular diseases are the leading cause of death in the Western World, especially in the elder population. One pathophysiological component of cardiovascular disease is myocardial fibrosis, primarily derived from cardiac fibroblasts. Here we investigated the regulation of proliferation of fibroblasts from hearts of adult rats by platelet derived growth factor AA (PDGF-AA). METHODS: Cardiac fibroblasts were isolated from adult Wistar rats. PDGF-induced cell proliferation was analysed by FACS. PDGF-receptor numbers were analysed by receptor binding assays. Using differential display, differentially expressed kinases were identified during ageing in vitro and confirmed by Northern and Western blotting. Transient overexpression of IRES-GFP constructs was used to analyse the role of the akt kinase on proliferation by FACS. RESULTS: During in vitro senescence/aging of primary fibroblasts, the growth response to PDGF-AA was greatly reduced without alterations in its receptor number or affinity and without changes in downstream signalling via the MAP-kinase pathway. By using a differential display strategy selective for protein kinases, we identified reduced expression of Akt-1 kinase (PKB-alpha) in senescent rat cardiac fibroblasts. These findings were supported by data showing reduced expression of Akt-1 in heart samples from old humans. Overexpression of activated Akt-1 almost completely reconstituted PDGF-AA dependent cell proliferation in aged fibroblasts. CONCLUSION: These results support an important role for Akt in senescence and regulation of cardiac fibroblast cell proliferation.

Animals↗
PubMed2001

Atrophy-metaplasia-dysplasia-carcinoma sequence in the stomach: a reality or merely an hypothesis?

The results of recent investigations have suggested that the old hypothesis of an atrophy-metaplasia-dysplasia-carcinoma sequence in the stomach needs to be qualified. The most common cause of intestinal metaplasia is Helicobacter pylori gastritis. The consequence of this intestinal metaplasia is focal atrophy. Helicobacter pylori infection may also trigger an autoimmune gastritis of the corpus mucosa, with atrophy and intestinal metaplasia. Most intestinal metaplasias are only 'paracancerous' but not 'precancerous' lesions. Diffuse gastric carcinomas, such as the signet ring cell carcinoma, arise independently of intestinal metaplasia. Histogenetically, numerous carcinomas of the stomach are primarily of the gastric type, and may secondarily change into the intestinal type.High-grade intra-epithelial neoplasias (dysplasias) detected during the biopsy-based diagnostic work-up appear to be a marker for carcinoma and must, therefore, be removed endoscopically. The detection of intestinal metaplasia in routinely obtained biopsy material is subject to sampling error and is, therefore, not a suitable marker for an increased risk of a gastric carcinoma developing. As an alternative, the concept of gastritis of the carcinoma phenotype, which is more frequently found in early gastric carcinomas and in the relatives of gastric carcinoma patients, has been developed. In this concept, the diffuse parameters of grade and activity of the gastritis in the antrum and corpus, which are independent of sampling error, are subjected to a comparative analysis. A risk gastritis of the carcinoma phenotype is diagnosed when the grade and activity of the gastritis in the corpus are at least equally as pronounced as in the antrum. Currently, this concept is being tested in a prospective ongoing study. Future studies must show whether, and if so which, immunohistochemical or molecular-genetically detectable changes can be applied as risk markers in the diagnostic work-up. Helicobacter pylori eradication probably does not lead to complete regression of the intestinal metaplasia and ensuing focal atrophy. However, eradication of H. pylori does lead to the normalization of changes that can lead to mutations of the stem cells of the gastric mucosa (free radicals, nitric oxide, cell proliferation and vitamin C secretion).

Gastric Mucosa↗
PubMed2001

[Study Group of Gastroenterological Pathology of the German Society of Pathology. Recommendations for celiac disease/sprue diagnosis].

The diagnosis of celiac disease (CD) is based upon histological findings in duodenal or jejunal biopsies. In the past few years it has turned out that the development of CD lesion in the small bowel is a dynamic process which may present in various histological forms. At one end of the spectrum is a mucosa with normal architecture and an increase in intraepithelial lymphocytes (IEL), at the other end is the classical flat mucosa. Histological features supporting the diagnosis of CD are architectural changes of the villi and/or crypts, an increase in lamina propria cell density and an increase in IEL counts. For diagnostic purposes and for monitoring of CD patients an exact histological classification of the histological findings has to be given. This has become possible by using a modified Marsh classification. In the present paper the histological presentation of CD is presented as well as the modified Marsh classification and the most important differential diagnoses.

Biopsy↗
PubMed2001

[Ulcerative esophagitis and colitis as rare manifestations of Adamantiades-Behcet disease].

We report the case of a 39-year-old German women who suffered from chronic inflammatory bowel disease which had not been exactly classified for 6 years. In the course of the disease she developed recurrent iritis, nodular skleritis, oral and genital ulcer, erythema nodosum and axillary folliculitis. For the first time retrosternal pain occurred. Endoscopy of the upper gastrointestinal tract showed mid esophageal ulcer formation. Colonoscopy demonstrated ulcerative colitis with no involvement of rectal mucosa. Histologically a cutaneous vasculitis in the lower limb was seen and diagnosis of Adamantiades-Behçet disease with marked gastrointestinal involvement and rare manifestation in the esophagus was established. A therapy with prednisolone, azathioprine and mesalazine was started. Under this regimen stomatitis, esophagitis and cutaneous vasculitis resolved, while the colitis showed partial remission now for up to one year.

Adult↗
PubMed2001

Improvement in the quality of the endoscopic/bioptic diagnosis of gastric ulcers between 1990 and 1997--an analysis of 1,658 patients.

BACKGROUND: Helicobacter pylori research has greatly improved the diagnosis and treatment of gastric ulcer. The aim of the present study was to investigate the question whether the new perceptions had been incorporated into the daily diagnostic routine of the nineteen-nineties. PATIENTS AND METHODS: Analysis of the biopsy material at the institute of Pathology of the Klinikum Bayreuth obtained from 1,658 patients with gastric ulcers in the months of January and February 1990 (n = 506), 1992 (n = 525), 1994 (n = 532), 1995 (n = 432) and 1997 (n = 400) with the aim of determining the quality of the endoscopic assessment of biological significance, and the number of biopsy specimens obtained from the ulcer, as well as the number of additional biopsies taken from the antrum and corpus. RESULTS: 1,436 (88.9%) of the endoscopically diagnosed ulcers proved to be histologically benign and 222 (11.1%) malignant, of which 192 (86.5%) were carcinomas, 24 (10.8%) MALT lymphomas, 2 (0.9%) sarcomas, and 4 (1.8%) ulcerated metastases. The percentage of false-negative endoscopic assessments of biological significance was 1.8%, that of the false-positive assessments 4.1%, that is, both very low figures. In the case of endoscopically suspicious findings, the histological examination revealed an ulcerated malignant tumor in almost 30% of the cases. The average number of biopsies harvested from the ulcer increased from 5.9 in 1990 to 7.1 in 1997. The frequency of biopsies obtained additionally from antrum and corpus rose statistically significantly from 14.1% of the cases in 1990 to 43.0% in 1997. CONCLUSION: During the course of the nineteen-nineties, the quality of the endoscopic/bioptic diagnosis improved noticeably. In terms of the number of biopsy specimens obtained from the ulcer to identify its biological significance, and the number of additional biopsies from antrum and corpus to identify underlying diseases, there is, however, still room for improvement.

Adolescent↗
PubMed2001

Short-term changes in Helicobacter pylori gastritis and bulbitis during and after 2 weeks of treatment with omeprazole and amoxicillin in duodenal ulcer patients.

OBJECTIVE: To evaluate the dynamics of histological changes in the mucosa of the stomach and duodenal bulb during and after completion of a 14-day course of Hp-eradication dual treatment with high-dose omeprazole and amoxicillin. PATIENTS: 12 patients (mean age 53 +/- 16 years SD, 9 male, 3 female) with an acute Hp-positive duodenal ulcer were included in this open, prospective, single-centre study. METHOD: Patients were given omeprazole 40 mg b.i.d. and amoxicillin 1,500 mg b.i.d. for a period of 14 days. Endoscopic biopsies were obtained on days 3, 7, 14, 28, 42 as well as at following endoscopies performed a mean of 17 months after treatment. RESULTS: The Hp-eradication rate achieved 4 weeks after treatment was 82%. On day 14, 88% of the ulcers were healed. Already on day 7 Hp had almost completely disappeared from the antrum, corpus and duodenal bulb, and the activity of gastritis in the antrum and corpus and the activity of bulbitis in the duodenal bulb was almost nonexistent. The decrease in the grade of gastritis was much lower by day 42. CONCLUSIONS: Our study shows for the first time that in all patients signs of primarily successful Hp-eradication treatment during the first days of treatment are consistently demonstrable and complete already after one week of therapy, irrespective of the subsequent cure or persistence of Hp-infection. In the patients with persistence of Hp-infection Hp-colonization and activity of gastritis quickly increased within 2-4 weeks after cessation of treatment. Checks to evaluate complete eradication or recrudescence of Hp-infection should be carried out not earlier than 28 days after cessation of treatment.

Adult↗
PubMed2001

Red streaks in the oesophagus in patients with reflux disease: is there a histomorphological correlate?

BACKGROUND: The Los Angeles classification of reflux oesophagitis includes sharply demarcated areas of erythema without any associated slough within the definition of reflux-induced mucosal breaks, though there is uncertainty as to whether these "red streaks" actually represent such a mucosal lesion. This study evaluates the histopathology of these red streaks. METHODS: Forty patients with one or more red streaks on the tops of the mucosal folds in the distal oesophagus were included in a multinational, multicentre prospective study. All patients were referred for upper gastrointestinal endoscopy to investigate chronic heartburn and acid regurgitation. Biopsies were taken from the red streaks and from control biopsies from more normal appearing mucosa 1 cm lateral to the red streaks. A two-sided probability test using normal approximation assessed differences in the histological findings at the two biopsy locations. RESULTS: Compared to control biopsies, biopsies of red streaks had a significantly thicker basal cell layer (mean +/- s 41% +/- 32% versus 18% +/- 23% of mucosal thickness, P=0.001) and longer papillae (mean +/- s 71% +/- 19% versus 49% +/- 24% of mucosal thickness, P= 0.001). Of the red streak biopsies, 25% had either newly re-epithelized lesions or granulation tissue beneath squamous epithelium. Only 10% of the control biopsies had moderate or more marked regenerative changes (based on elongation of papillae and basal cell hyperplasia), compared to 65.1% of red streak biopsies. Of the biopsies from the red streak itself, 7% showed no abnormality and 27.9% only slight changes. In comparison, 25% of the biopsies from control biopsies showed no regenerative changes and 62.5% only slight change due to gastro-oesophageal reflux disease. CONCLUSION: The histomorphological counterpart to the endoscopically visible red streaks of the distal oesophagus is marked regenerative changes of the squamous epithelium and/or capillary rich granulation tissue beneath the squamous epithelium. Red streaks are validated as being indicative of acid/peptic mucosal injury, but they do not satisfy a strict definition of a mucosal break.

Biopsy↗
PubMed2001

Acute measles gastric infection.

We describe the case of a 44-year-old man who was referred for gastroscopy because of abdominal pain. During endoscopy, inflammatory changes of the antrum and corpus mucosa were clearly visible, and biopsy samples from the antrum and corpus mucosa were taken. At histology, routine hematoxylin and eosin staining showed characteristics indicative of so-called ex-Helicobacter pylori-gastritis that had developed after antibiotic treatment 2 years ago. Additional large, bizarre inclusion bodies and clusters of multinucleated giant cells were located in the surface epithelium and within the lamina propria. These giant cells had an appearance similar to that of Warthin-Finkeldey cells, which can be found during the prodromal phase of measles infection. Anti-measles virus immunochemistry showed a strong positivity for measles virus antigen within the giant cells. Based on these results, the final diagnosis of morbilliform gastritis was made. To our knowledge, no case of measles gastritis has been described in the literature. Our case report confirms the systemic character of measles virus infection and confirms that measles viral replication can involve the gastric mucosa in addition to the conjunctiva, lung, and intestina.

Acute Disease↗
PubMed2001

The AMOR study: a randomized, double-blinded trial of omeprazole versus ranitidine together with amoxycillin and metronidazole for eradication of Helicobacter pylori.

BACKGROUND: Besides antibiotics, additionally effective acid inhibition is necessary for the eradication of Helicobacter pylori. OBJECTIVE: To assess the significance of acid suppression and, in particular, treatment with proton pump inhibitors (PPIs) compared with H2 receptor antagonists (H2 RAs). The primary target parameter for the study was H. pylori eradication. In addition, the ulcer healing rate, speed of pain reduction, score for gastritis in the antrum and gastric body, and rate of side effects were recorded. DESIGN: Randomized, double-blinded, multicentre study. PARTICIPANTS: A total of 456 patients between the ages of 18 and 80 years with H. pylori-positive duodenal ulcers were included in the study. METHODS: Using a randomization list, patients were assigned either to a treatment group receiving omeprazole 40 mg once daily, amoxycillin 750 mg three times a day, and metronidazole 500 mg three times a day (OAM), or to a group receiving ranitidine 300 mg once daily, amoxycillin 750 mg three times a day, and metronidazole 500 mg three times a day (RAM). The treatment period was 7 days in both groups. Long-term acid-suppressant treatment was not given. RESULTS: The eradication rate was 87.1% (169/194, intention to treat [ITT]) in the OAM group and 77% (137/ 178, ITT) in the RAM group. The difference of 10.1% (95% CI 2.5-18%) is statistically significant (P= 0.0104). The ulcer healing rate was 93.3% in the OAM group (181/194, ITT) and 92.1% in the RAM group (164/178, ITT, NS). With regard to the speed and intensity of pain reduction, the OAM group was superior to the RAM group. In patients in whom H. pylori eradication was successful, the reduction in the antral and gastric body gastritis score was significantly greater than in patients without eradication. In the OAM group, 39.1% of the patients (n = 90) reported one or more side effects, compared with 44.7% (n = 101) in the RAM group (P= 1.5449, NS). CONCLUSION: Omeprazole (40 mg once daily in the morning) is significantly more effective than ranitidine (300 mg once daily in the morning) with respect to H. pylori eradication when used together with amoxycillin (750 mg three times a day) and metronidazole (500 mg three times a day) for a 7-day treatment period.

Adolescent↗
PubMed2001

Helicobacter pylori vacA, iceA, and cagA status and pattern of gastritis in patients with malignant and benign gastroduodenal disease.

OBJECTIVE: Both bacterial virulence factors and the pattern of Helicobacter pylori (H. pylori) gastritis may contribute to the development of clinically relevant gastroduodenal disease. The aim of our study was to investigate the frequency of H. pylori vacA alleles, iceA, and cagA, and the pattern of gastritis in patients with gastric cancer (GC), gastric lymphoma (MALT), duodenal ulcer (DU), and functional dyspepsia (FD). METHODS: H. pylori was cultured from 141 patients (34 GC, 26 MALT, 49 DU, 32 FD). Allelic variants of vacA and iceA, and cagA were identified by polymerase chain reaction. Antrum and corpus biopsies were obtained for assessment of gastritis according to the updated Sydney System. RESULTS: The vacA sl,ml genotype was more frequently detected in H. pylori from GC patients (70.6%) than from MALT, DU, and FD patients (p < 0.05). The frequency of iceA1 and cagA did not differ among the groups. The proportion of patients with severe gastritis in the corpus was significantly higher in patients with GC and MALT compared with patients with DU (p < 0.001). CONCLUSIONS: In a German patient population, only the vacA s1,m1 genotype of H. pylori is associated with GC, and therefore may be useful to identify infected patients being at an increased risk for GC.

Aged↗
PubMed2001

Inducible nitric oxide synthase expression before and after eradication of Helicobacter pylori in different forms of gastritis.

An increased expression of inducible nitric oxide synthase (iNOS) has been observed in the inflamed human gastric mucosa as well as in some tumors. This observation suggests a pathobiological role of elevated NO production. The purpose of this study was to compare the immunohistochemical iNOS expression in the different kinds of gastritis before and after the eradication of Helicobacter pylori. We performed iNOS and H. pylori immunohistochemical staining and counted iNOS positive cells. We detected elevated expression of iNOS around sites infected with H. pylori. iNOS expression in chemical gastritis was strongly elevated in mucosal glands. After treatment, we found a significant difference in iNOS expression in patients with classical H. pylori-induced antrum predominant gastritis and in patients with active autoimmune gastritis. In the special case of progressed gastritis with intestinal metaplasia we found persistence of intestinal metaplasia, and we could not find a significant difference in the number of positive iNOS cells before and after treatment. The persistence of IM as a possibly precancerous lesion is probably at least in the antrum a source of continuous iNOS induction even after H. pylori eradication.

Adult↗
PubMed2001

Comparison of CXC chemokines ENA-78 and interleukin-8 expression in Helicobacter pylori-associated gastritis.

Colonization of the gastric mucosa with Helicobacter pylori is associated with a dense infiltration of granulocytes into the lamina propria in the active phase of gastritis. In this study, we investigated the involvement of epithelial cell-derived neutrophil-activating protein 78 (ENA-78) in development of H. pylori-associated gastritis. Antral biopsies from 27 patients with H. pylori-associated gastritis and 25 from H. pylori-negative individuals were first analyzed for ENA-78 and interleukin-8 (IL-8) mRNA by semiquantitative reverse transcription (RT)-PCR. In H. pylori-positive patients, significantly elevated levels were found for both chemokines (P<0.05). Only IL-8 mRNA levels differed significantly (P<0.05) in H. pylori-infected individuals who had serum antibodies for cytotoxin-associated protein CagA versus H. pylori-infected CagA-negative persons. Quantification of ENA-78 transcript levels by competitive RT-PCR yielded a significant 45-fold upregulation for ENA-78 transcripts in biopsies of H. pylori-positive versus H. pylori-negative patients (P<0.05). In contrast to earlier findings with IL-8, the degree of ENA-78 mRNA upregulation was independent of the grade of activity of gastritis. Immunofluorescence studies on tissues of antral biopsies localized ENA-78 protein expression mainly to the gastric epithelium of H. pylori-positive patients, while control tissues were negative. Upregulation of ENA-78 and IL-8 mRNA and protein expression was also observed in an in vitro system using a gastric adenocarcinoma cell line. Only viable H. pylori yielded a strong ENA-78 and IL-8 induction, while H. pylori outer membrane proteins or water-soluble proteins had no significant effect. These data provide evidence for the importance of both IL-8 and ENA-78 in the development and perpetuation of H. pylori-associated gastritis.

Antigens, Bacterial↗
PubMed2001

Specific detection and prevalence of Helicobacter heilmannii-like organisms in the human gastric mucosa by fluorescent in situ hybridization and partial 16S ribosomal DNA sequencing.

Gastric infection with Helicobacter heilmannii (previously known as Gastrospirillum hominis) is invariably linked with the presence of chronic gastritis and the risk of developing low-grade mucosa-associated lymphoid tissue lymphoma in humans. In contrast to Helicobacter pylori, various H. heilmannii species colonize the stomachs of domestic animals, which might be a reservoir for transmission to humans (zoonosis). To identify the number and prevalence of different H. heilmanni types in humans, we analyzed 89 gastric biopsy samples histologically identified as H. heilmannii positive by fluorescence in situ hybridization. Of these gastric specimens, 84 (94.4%) contained a single H. heilmannii type. In five samples, however, two different H. heilmannii types were detected. The most prevalent species in monoinfected samples is H. heilmannii type 1, found in 78.5% (66 of 84) of the specimens, followed by a novel H. heilmannii-like organism (HHLO), HHLO type 4, identified in 9.6% (8 of 84) of tissue sections. H. heilmannii type 2 and a further HHLO type not described before, type 3, were found in 8.3% (7 of 84) and 1.2% (1 of 84) of the monoinfected samples, respectively. Additionally, HHLO type 5 with a 16S ribosomal DNA sequence identical to that of Helicobacter salomonis was found with a prevalence of 2.4% (2 of 89). Thirteen of these biopsy samples were also investigated by a PCR approach developed for this study that allows a Helicobacter-specific amplification of a variable portion of the 16S rRNA gene and subsequent sequencing. In total, five different types of HHLOs could be identified within these samples. We conclude that humans can be infected by at least five different HHLO types, which presumably have their origin in animal species like dogs, cats, and pigs.

Biopsy↗