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A Tannapfel

Publications and source records attributed to A Tannapfel.

At least 37 records · Page 2Linked to original sources

A novel model of fibroblast-mediated cartilage destruction.

In rheumatoid arthritis (RA), fibroblasts have been shown to be crucial for disease progression as well as joint destruction. In the model of human/murine SCID arthritis, synovial explants as well as fibroblasts from human rheumatoid synovial membrane induce destructive arthritis in immunodeficient mice. Hereby, the underlying cartilage destruction is accomplished by murine fibroblasts. Therefore, murine destructive fibroblasts represent a promising tool to investigate destruction of articular cartilage and bone. In this context, a novel destructive murine fibroblast line (LS48) was examined for morphological, ultrastructural, immunological and functional cellular parameters. These cells were injected into knees of SCID mice. Subsequently, the animals were monitored for joint swelling and serological parameters of arthritis by radiological methods. Finally, cartilage destruction was assessed morphologically. Cultured LS48 cells exhibit characteristic features that resemble those of activated synovial fibroblasts in human RA. Expression levels of inducible nitric oxide synthase, interleukin-6, tumour necrosis factor-alpha and matrix metalloproteinases were comparable to those detected in invasive human fibroblasts. The instillation of 5 x 10(5) LS48 cells into the knee joints of SCID mice initiated a rapid progressive process, that caused cartilage destruction within 10 days, and morphological examinations revealed that articular cartilage was infiltrated by the fibroblasts injected previously. In summary, the intra-articular application of LS48 cells represents a rapid and highly reproducible model to investigate the initiation and progression of cartilage destruction in connection with RA therapy and represents an easy-to-handle animal model.

Animals↗

Promoter methylation and loss of coding exons of the fragile histidine triad (FHIT) gene in intrahepatic cholangiocarcinomas.

AIMS: About 10-30% of primary liver cancers represent intrahepatic cholangiocarcinomas (IHCC). Since chromosomal losses of 3p are detectable in about 40% of cholangiocarcinomas our study aimed at the identification of mechanisms leading to functional deletion of tumor suppressor genes in this region. Our efforts focussed on genomic losses and epigenetic inactivation of two tumor suppressor genes, the fragile histidine triad (FHIT) and the ras association domain family 1 (RASSF1A) genes, both located on the short arm of chromosome 3. METHODS: Methylation-specific PCR (MSP) and combined bisulfite-dependent restriction analysis (COBRA) were applied to detect epigenetic silencing of gene promoters. Genomic duplex PCR was used to identify exon losses of the FHIT gene. Nineteen paraffin-embedded samples of intrahepatic cholangiocarcinomas were studied. RESULTS: Here we report for the first time that in addition to frequent losses of the exons 5 and 6, hypermethylation of the FHIT promoter occured in a significant portion of IHCC. Methylation specific PCR (MSP) detected epigenetic inactivation of the FHIT/FRA3B locus in 8 of 19 (42%) cases. Combined bisulfite restriction analysis (COBRA) revealed that high levels of methylated FHIT promoter sequences were present in 6 of the 8 methylation positive samples. In agreement with previous reports MSP identified hypermethylation of the RASSF1A gene in 13 of 19 (68%) IHCC specimens examined. CONCLUSIONS: Epigenetic silencing of the FHIT tumor suppressor gene is a novel inactivation mechanism to be considered in the development of intrahepatic cholangiocarcinomas. However, a statistically significant inverse correlation between K-Ras activation and RASSF1A inactivation was not found.

Acid Anhydride Hydrolases↗

Investigation of arthritic joint destruction by a novel fibroblast-based model.

The key pathologic mechanism in rheumatoid arthritis (RA) is the destruction of cartilage by fibroblasts. In a severe combined immunodeficient (SCID) mouse model, this process can be modulated by gene transfer using invasive LS48 fibroblasts. This study aims to investigate the effect of interleukins (IL) -11 and -12 on cartilage destruction when transferred into LS48, and of IL-15 when transfected into non-invasive 3T3 cells; to compare three transduction systems (a lentiviral vector system, a retroviral vector system, and a particle-mediated gene transfer); and to establish an in vitro cartilage destruction system based on LS48 cells. Transduced fibroblasts were injected into SCID mice knee joints, and disease progression assessed microscopically. Distinctive morphologic pattern revealed invasion of fibroblasts into the articular cartilage by transfected, as well as non-transfected, LS48 cells. IL-12 and IL-15 did not alter swelling or cartilage destruction. Animals treated with IL-11-transfected cells showed reduced cartilage damage but no changes in swelling. Efficacy of gene transfer to establish transfected fibroblasts was shown to be >85% for lentiviral transfer, compared to <10% for retroviral transfer and gene gun. Furthermore, cells were co-incubated with porcine cartilage. Transduction of IL-11 led to a reduction of apoptosis in chondrocytes. These findings suggest that cartilage destruction by invasive fibroblasts can be modulated by gene transfer. Lentiviral vector systems offer the most effective approach for gene transduction. In vitro fibroblast/cartilage co-cultures present a convenient system for the assessment of novel therapeutic strategies toward reduction of articular destruction.

3T3 Cells↗

[Gallbladder and bile duct carcinoma. Biology and pathology].

Biliary tract cancers are a consequence of a stepwise malignant transformation of the biliary epithelium. Intrahepatic cholangiocarcinomas arises from any portions of the intrahepatic bile duct epithelium: the segmental or area ducts and their finer branches or intrahepatic small bile ducts. Cholangiocarcinoma arising from the hepatic ducts or near their junction are called hilar cholangiocarcinoma or Klatskin tumour, and are considered as extrahepatic lesion. Cancer of extrahepatic bile ducts may also arise in the Ductus cysticus or choledochus as well as in the gall bladder. For intrahepatic cholangiocarcinoma, the UICC-TNM classification system of malignant liver tumors is applied, differing from the UICC-TNM staging system of extrahepatic bile ducts and gall bladder carcinomas. The cause of carcinomas of the bile ducts remains speculative in most cases. However, chronic inflammation due to sclerosing cholangitis, hepatolithiasis or parasites is associated with carcinogenesis. Histopathologically, the vast majority are adenocarcinomas; mesenchymal tumors and primary melanomas are extremely rare. Different genetic alterations are discussed to be of importance.

Adenocarcinoma↗

[35-year old male with fever and round mass of the liver].

A 35 year old male suffered from fever till 39 degrees C and malaise since 6 months; infectious or neoplastic causes have been ruled out. Ultrasonography revealed a hypoechoic lesion of 75 mm diameter in the liver. The histologic examination of the needle biopsy showed an inflammatory process, and the final diagnosis was inflammatory pseudotumor. EBV specific LMP-1 protein was detected within the tumor immunohistochemically. A liver segment resection was performed, and the patient has been well and without fever since then for 18 months. Inflammatory pseudotumor is a rare but important differential diagnosis in cases of hypoechoic liver lesions associated by fever, if there is no abscess or malignancy. The diagnosis must be confirmed histologically, because imaging techniques cannot reliably classify the lesion.

Adaptor Proteins, Signal Transducing↗

[Unclear liver fibrosis in a 42-year-old patient with polycythemia vera].

A 42-year-old patient was admitted to hospital because of ascites and polyglobulia. Laboratory tests revealed reduced liver function and a significant elevation of all three hematopoietic cell lines. Liver fibrosis and polycythemia vera were diagnosed by histologic examination. The most frequent causes for liver fibrosis were serologically excluded. Ultrasound combined with Doppler imaging revealed an obstruction of the right hepatic vein, which was indicative of Budd-Chiari syndrome. BCS can occur under fulminant and nonfulminant conditions, which can result in progressive damage of the liver. Phlebotomy and combined therapy with low-dose aspirin and anagrelide achieved permanent reduction of the elevated blood parameters. In the follow-up the patient's clinical course was stable without hepatic decompensation.

Adult↗

[Immunohistochemical localization of matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in tuberculous pleuritis].

Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) have been found by ELISA and gelatine zymography in different concentrations in pleural fluid in tuberculous (TB) pleuritis. For further differentiation MMP and TIMP were localized in pleural biopsies by immunhistochemical staining with antibodies directed against MMP-1, MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 using the Labelled-Avidin-Biotin (LAB). Immunohistological reactivity of MMP-1 was found in epitheloidcellular histiocytes, Langhans' giant cells, lymphocytes, macrophages, as well as in fibroblasts of granulomatous reactions. MMP-2 was found in a few epitheloid cellular histiocytes, fibroblasts, and inflammatory cells. MMP-3 was weakly positive in a few lymphocytes only. MMP-9 was found in a few fibroblasts, epitheloid cells, and inflammatory cells, foremost, however, in pleural mesothial cells. A few fibroblasts only showed immunoreactivity of TIMP-1 and TIMP-2. The observed inhomogenous staining pattern could be explained by the different state of activation of individual cellular units. In conclusion, the immunohistochemical demonstration of MMP and TIMP in pleural cells and tissue structures indicates their local involvement in fibrosing reactions in TB-pleuritis.

Female↗

In vivo studies comparing the biocompatibility of various polypropylene meshes and their handling properties during endoscopic total extraperitoneal (TEP) patchplasty: an experimental study in pigs.

BACKGROUND: Polypropylene (PP) meshes are currently being used in millions of operations for hernial repair. We tested several recently modified PP meshes to evaluate them in terms of their biocompatibility and handling characteristics during minimally invasive procedures. METHODS: Four different PP meshes (a heavyweight PP, Atrium; a lightweight PP incorporating absorbable polyglactic acid, Vypro II; a lightweight PP, Parietene; and a titanium-coated lightweight PP, Ti-Mesh Extralight), all implanted using the endoscopic total extrapreperitoneal (TEP) technique, were investigated in groups comprising 11 pigs each. After 94 +/- 5 days, the animals were autopsied and tissue samples were studied histologically, immunohistochemically, and electron-microscopically. RESULTS: Whereas endoscopic handling of the Vypro II mesh proved difficult, the already good properties of the Atrium mesh were significantly improved on by Parietene and the Ti-Mesh. Clear differences were also found in the shrinkage characteristics of the implant materials. In comparison with Atrium (12%), Vypro II mesh shrinkage was significantly greater (28%), whereas Parietene (7%) and Ti-Mesh (5%) incurred less shrinkage. With regard to the chronic inflammatory reaction, the titanium-coated mesh showed a significantly lower inflammatory activity (13.1% partial volume [%PV] vs 34.1%PV and 29.0%PV) than the lightweight meshes Vypro II and Parietene, but-with the exception of the monocytic (0.2 vs 9.1, 5.1, and 7.9) and B-lymphocytic reaction (1.1 vs 18.0, 11.7, and 12.2)-no significant difference was seen in comparison with Atrium. The various mediators in the extracellular matrix (matrix metalloproteinases 1 [MMP-1 transforming growth factor beta [TGF-beta], urokinase plasminogen activator [uPA], and type I collagen) tended to show the highest expression with Vypro II (13.6, 113.2, 132.7, and 139.5, respectively) and the lowest expression with Ti-Mesh (11.9, 68.5, 92.8, and 75.0, respectively). With regard to cell proliferation, Parietene and Ti-Mesh appeared to have slight advantages, but no differences were observed in the apoptotic rate. CONCLUSION: In our opinion, despite a reduction in material, Vipro II, on account of the inflammatory reaction, does not represent a true improvement over the meshes currently used for hernia repair. In comparison, the two lightweight PP patches are characterized by a more favorable foreign body reaction, with the titanium coating of the Ti-Mesh providing an additional advantage in terms of its biocompatibility.

Abdominal Wall↗

[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↗

[Regression grading of colorectal carcinoma after preoperative radiochemotherapy. An inventory].

The treatment of patients with colorectal cancer has changed over the last decades. More and more patients receive combined modality treatments including (preoperative) radiotherapy and chemotherapy. To assess the colorectal cancer specimen after neoadjuvant therapy, the pathologist has to be familiar with the histological features induced by radiochemotherapy. Performing a standardized pathological procedure, different grades of tumour regression can be observed and tumour staging should be standardized using valid and reproducible criteria. These criteria are recommended in the forthcoming TNM classification (6th edition, 2002). In the review, these classification rules will be discussed for rectal cancer.

Colonic Neoplasms↗

[Sporadic acute hepatitis E in Germany: an underdiagnosed phenomenon?].

Hepatitis E virus infection is the leading cause of enterically transmitted hepatitis worldwide. Case reports of hepatitis E in individuals in Germany so far related to travel to endemic areas. A 33-year-old man presented with painless jaundice. By serology and liver biopsy, no cause of hepatitis could be identified. After discharge transaminases were persistently elevated. Serology (IgG and IgM) confirmed acute hepatitis E. The transaminases declined to normal values within six months. Detailed anamnestic questioning revealed no travel to an endemic region or contact with individuals who had visited such areas. In addition to our patient, a total of 34 cases of acute hepatitis E were reported to the Robert-Koch-Institute (German center of disease control) in 2001. In five of them, the disease had obviously been acquired in Germany. These data indicate that community acquired hepatitis E virus infection may occur sporadically in Germany and should be considered as a cause of seronegative (non-A-non-B-non-C) hepatitis.

Acute Disease↗

[MRI-guided pediatric interventions].

AIM: There are only a few diagnostic or therapeutic procedures where MR imaging is applied during pediatric interventions. This study will describe indications, complications as well as the advantages and disadvantages of MRI-guided interventions based on a case study in an open MRI scanner. MATERIALS AND METHODS: 14 procedures were performed in an open MRI scanner (Signa SP/i, GEMS) on 13 children (1 - 16 yr) with bone, soft tissue and brain lesions (1 - 4 cm diameter). Localization of the pathology, targeting and final control of the result were based on images acquired with SE-, 3D-, GE-sequences pre- and post-contrast as well as FSE-sequences. Interactive MRI-guided instrument navigation was performed using a multiplanar T1w GE-sequence. RESULTS: Eight biopsies (incl. 1 rebiopsy), two tumor resections, one removal of a free joint mouse and three tumor-markings were performed without complications. Five biopsies provided appropriate sample quality for a histological diagnosis while two samples were too fragmented requiring a second biopsy (one of them MRI-guided). Surgical progress during tumor resection and marking could be controlled during the intervention without repositioning the patient. DISCUSSION: MR image guided pediatric interventions combine the advantage of an imaging system without ionizing radiation and the high soft-tissue contrast. The low number of these kinds of procedures can be explained by the relatively high costs for the intervention, the increased duration for each procedure and the limited availability of open MRI systems. The integrated localization-system helps during planning of the access path when facing complex anatomical structures and provides safe navigation in sensitive regions like the epiphyseal cartilage. Recent and expected developments of the required MR-compatible biopsy instruments could provide higher efficiency for appropriate sample size and quality. Summarizing, MRI-guided pediatric interventions have shown to be a promising method at the beginning of its development.

Adolescent↗

Histopathological parameters of Helicobacter pylori-associated gastritis in children and adolescents: comparison with findings in adults.

BACKGROUND: The pathohistological features of Helicobacter pylori-associated gastritis in children and adolescents are less well understood than they are in adults. The aim of the study was to compare histological parameters of H. pylori-infected children with those of adults. METHODS: The retrospective study compared histological features of 111 children (mean age 10.8 +/- 3.8). Three paediatric age groups were analysed and the findings were compared with those of 111 adults (mean age 64.2 +/- 12.1). Degree of chronicity and activity of inflammation, mucus depletion and regeneration of foveolar epithelium by regenerating epithelium and H. pylori colonization were scored in antral biopsies. RESULTS: The histological parameters in children, i.e. degree of chronicity, activity of gastritis and the summed gastritis score, were not significantly different compared to those in adults. Replacement of foveolar epithelium by regenerating epithelium was significantly larger in adults compared to that of paediatric patients. The rate of low-grade mucus depletion and of the strongest degree of H. pylori colonization was higher in children than in adults. Children with antral nodularity had significantly higher histological score values. CONCLUSION: The histological differences between paediatric patients and adults are focused on signs of chronic inflammation and regeneration. Our results imply that antral nodularity is an important sign of highest-grade gastritis, especially in young children.

Adolescent↗