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T Kirchner

Publications and source records attributed to T Kirchner.

At least 55 records · Page 3Linked to original sources
PubMed2000

Effective isolation of high-quality total RNA from human adult articular cartilage.

The isolation of large quantities of good-quality RNA from human articular cartilage has been a long-standing problem for researchers working with human articular cartilage. In this paper we report a protocol which we have developed based on the Qiagen RNeasy procedure to produce high yields of purified, DNA-free RNA from normal and osteosteoarthritic human articular cartilage. The average yield of RNA was 8.39 microg/g (n = 59) for normal and 6.69 microg/g (n = 58) for osteoarthritic cartilage (average ratio OD 260/280 = 1.8-1.9). Quantitative PCR, cDNA array technology, and Northern blot analysis were used to verify the quality of the RNA.

Adult↗
PubMed2000

Squamous cell carcinoma of the oropharynx: Ki-67 and p53 can identify patients at high risk for local recurrence after surgery and postoperative radiotherapy.

PURPOSE: To assess the prognostic value of biologic (p53, Ki-67) and clinical factors in squamous cell carcinoma of the oropharynx after radical surgery and postoperative radiotherapy (RT). METHODS AND MATERIALS: Between 1985 and 1995, a total of 102 patients with 104 tumor sites were entered onto the study. Fifty-five primary tumors (53%) involved the tonsils, 26 (25%) the soft palate, and 23 (22%) the base of the tongue. Median age was 53 years (range 36-80 years). The clinical T- and N-categories (UICC 1997) were: T1 (30), T2 (47), T3 (22), T4 (5), N0 (33), N1 (28), N2 (42), and N3 (1). Histologically-clear margins were achieved in all patients by initial surgery. Postoperative RT to the primary and regional lymphatics was given, to a total of 60 Gy in 6 weeks, and single daily fractions of 2 Gy. The expression of the nuclear p53- and Ki-67-labeling index (LI) was investigated by immunostaining using the monoclonal antibodies DO-7 and MIB 1. The nuclear p53-intensity (p53-I) was graded into 4 categories (0/+/++/) by densitometry. Median follow-up was 43 months (range 14-132 months). RESULTS: Cancer-specific survival, disease-free survival, and locoregional tumor control rates were 74%, 69%, and 75%, respectively, at 5 years. Significant prognostic factors for disease-free survival were: T-category (T1/2: 77% vs. T3/4: 53%, p = 0.02), tumor site (tonsils: 79% vs. soft palate: 70% vs. base of tongue: 45%, p = 0.05), duration of RT (< or = 46 days: 80% vs. > 46 days: 60%, p = 0.04), Ki-67 LI (< or = 20%: 84% vs. > 20%: 49%, p = 0.006) and p53-I (0/+: 56% vs. ++/ : 79%, p = 0.008). A significant prognostic impact on locoregional control was noted for the duration of RT (< or = 46 days: 86% vs. > 46 days: 68%, p = 0.01), tumor site (tonsils: 88% vs. soft palate: 67% vs. base of tongue: 51%, p = 0.02), Ki-67 LI (< or = 20% LI: 87% vs. > 20% LI: 56%, p = 0.018), and the p53-I (0/+: 58% vs. ++/ : 88%, p = 0.0006). On multivariate analysis, the p53 nuclear intensity (p = 0.002) and the Ki-67 index (p = 0.01) remained the only significant factors for locoregional control. CONCLUSION: Ki-67 labeling index above 20% and a weak p53 nuclear intensity (0/+) are both able to identify patients with squamous cell carcinoma of the oropharynx being at high risk for local recurrence after surgery and postoperative RT. Consequently, in this subgroup an intensification of treatment may be contemplated in prospective trials.

Adult↗
PubMed2000

Herpesvirus saimiri-transformed macaque T cells are tolerated and do not cause lymphoma after autologous reinfusion.

Human T cells are transformed in vitro to stable growth after infection with herpesvirus saimiri subgroup C strain C488, and they retain their antigen-specific reactivity and other important functional features of mature activated T lymphocytes. The virus persists as nonintegrating episomes in human T cells under restricted viral gene expression and without production of virus particles. This study analyzes the behavior of herpesvirus-transformed autologous T cells after reinfusion into the donor under close-to-human experimental conditions. T cells of 5 macaque monkeys were transformed to stable interleukin-2 dependent growth and were intravenously infused into the respective donor. The animals remained healthy, without occurrence of lymphoma or leukemia for an observation period of more than 1 year. Over several months virus genomes were detectable in peripheral blood cells and in cultured T cells by polymerase chain reaction. In naive control animals, a high-dose intravenous infection rapidly induced pleomorphic peripheral T-cell lymphoma. In contrast, monkeys were protected from lymphoma after challenge infection if they had previously received autologous T-cell transfusions. High levels of antibodies against virus antigens were detectable after challenge infection only. Taken together, herpesvirus-transformed T cells are well tolerated after autologous reinfusion. This may allow us to develop a novel concept for adoptive T-cell mediated immunotherapy.

Adoptive Transfer↗
PubMed2000

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↗
PubMed2000

Oculocerebral non-Hodgkin's lymphoma with uveal involvement: development of an epibulbar tumor after vitrectomy.

Primary ocular lymphoma is the ocular manifestation of primary oculocerebral non-Hodgkin's lymphoma. We describe a 79-year-old woman with a 7-year history of bilateral uveitis and subsequent central nervous system lymphomas. Repeated diagnostic vitrectomy during the following 5 years failed to demonstrate intraocular lymphoma cells. Within 9 months after the second vitrectomy, an epibulbar tumor developed in the limbal region of the left eye at the site of the sclerotomy. The eye, blind and painful due to secondary angle-closure glaucoma, was enucleated. Histopathologically, the globe showed a diffuse large B-cell non-Hodgkin's lymphoma extending from the ciliary body outward through the sclerotomy. We conclude that, following vitrectomy, a primary ocular lymphoma may extend through the sclerotomy lesion and present as an epibulbar tumor. Uveal involvement may occur in oculocerebral non-Hodgkin's lymphoma.

Aged↗
PubMed2000

Hodgkin's disease and peripheral T-cell lymphoma: composite lymphoma with evidence of Epstein-Barr virus infection.

This paper reports the case of a patient with a composite lymphoma consisting of nodular sclerosing Hodgkin's disease and peripheral T-cell lymphoma. The Hodgkin and Reed-Sternberg (HRS) cells harboured the Epstein-Barr virus (EBV) and displayed a type II EBV latency (LMP1(+)/EBNA2(-)), whereas the neoplastic T-cells were EBV-negative. Four years later, the patient presented with a relapse of the peripheral T-cell lymphoma. In situ hybridization revealed numerous EBV-carrying lymphocytes, which were shown to be polyclonal B-cells with a latency III pattern of EBV gene expression (LMP1(+)/EBNA2(+)). This observation suggests that impairment of EBV-specific immunity in the micro-environment of T-cell lymphomas may facilitate the outgrowth of EBV-carrying B-lymphocytes and emphasizes the importance of determining the phenotype of EBV-infected cells, particularly when studying T-cell lymphomas. The results further suggest that the HRS cells and neoplastic T-cells were of different clonal origins. The detection of EBV-carrying cell populations admixed with the neoplastic T-cells at primary presentation and at relapse raises the possibility that the growth of the T-cell lymphoma was dependent on the presence of such cells.

Aged↗
PubMed2000

Lack of evidence for an involvement of Epstein-Barr virus infection of synovial membranes in the pathogenesis of rheumatoid arthritis.

OBJECTIVE: To test the hypothesis that Epstein-Barr virus (EBV) infection of cells within the synovial membrane contributes to the pathogenesis of rheumatoid arthritis (RA). METHODS: Biopsy samples of synovial membrane from 37 patients with RA and from 51 patients with other joint diseases were studied for evidence of EBV infection using in situ hybridization specific for the EBV-encoded RNAs (EBERs). Latent membrane protein 1 (LMP1) and the lytic-cycle BZLF1 protein were detected by immunohistochemistry. RESULTS: Rare EBER-positive B lymphocytes were detected in 7 RA biopsy samples. EBV was not detectable in any other cells. Expression of the LMP1 and BZLF1 proteins of EBV was not observed in any of the samples. No EBV infection was detected in synovial membranes from patients with other joint diseases. CONCLUSION: Our data indicate that EBV infection is not directly involved in the pathogenesis of RA. Any contribution of EBV to the pathogenic process leading to RA is likely to be indirect.

Adult↗
PubMed2000

p27(kip1) expression in rectal cancer correlates with disease-free survival.

BACKGROUND: The cell-cycle inhibitor p27(kip1) is a potential tumor suppressor and might serve as a prognostic marker in rectal cancer, in particular with regard to patient selection for adjuvant therapy. MATERIALS AND METHODS: Immunohistochemical analysis was performed, using an anti-p27(kip1) monoclonal antibody, on paraffin sections of two matched [age, gender, UICC stage, year of operation (1982-1991)] groups of patients (n = 2 x 82) with rectal carcinoma curatively treated by surgery alone. The groups differed only in subsequent metachronous distant metastatic spread. All patients had to meet the selection criterion "free of local disease," in order to exclude surgical influence. Follow-up was prospective (median of 74 months). The intensity of staining (-, +, ++, ) and rate of positive cells (as a percentage of total tumor volume) were judged separately for cytoplasms and nuclei. RESULTS: On multivariate analysis, cytoplasmic staining intensity proved to be the best prognostic factor of disease-free survival and approached statistical significance (P = 0.0552, Cox regression). On univariate analysis, considering cytoplasmic staining alone, intensely stained ( ) tumors showed significantly poorer disease-free survival (vs ++, +, -; Kaplan-Meier, logrank, P = 0.0185). CONCLUSIONS: The demonstrated correlation between cytoplasmic compartmentalization of p27(kip1) and increased metastatic spread as well as disease-free survival underscores the role of p27(kip1) in rectal cancer. However, since other reports emphasize the importance of nuclear p27(kip1) expression, the mechanisms of steady-state and subcellular distribution of p27(kip1) remain unclear, and further investigation is needed.

Adenocarcinoma↗
PubMed2000

[Effect of different factors on the bone forming properties of recombinant BMPs].

The extent of BMP-induced new bone formation is mainly determined by the number of mesenchymal target cells in the recipient bed as well as by the biological half-life of the BMP molecules within the tissue. While the number of inducible cells is determined by the age and vascularization of the tissue, the retention time of the BMP molecules can be influenced. One possibility is the coupling of BMPs to suitable carriers, which significantly increases the osteoinductive effect. The reason for this is the physical binding of BMPs to the carrier material, which delays the resorption of the proteins. Other factors are the composition of the carrier materials, their structural stability, and possible dislocations of carrier particles. The local tissue concentration of BMPs can also be increased by an enhanced binding of the proteins to the extracellular matrix. A BMP-2 mutant (BMP-2xa) was produced by the specific modification of the amino acid sequence using recombinant technologies. BMP-2xa induces heterotopic bone formation at significantly lower concentrations than natural BMP-2. Furthermore, BMP-2xa-induced bone tissue possesses a higher bone density.

Animals↗
PubMed2000

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↗
PubMed2000

Patterning and nuclear beta-catenin expression in the colonic adenoma-carcinoma sequence. Analogies with embryonic gastrulation.

Patterning is a process by which ordered arrangements of cells and tissue structure are attained. The term derived from developmental biology is also useful for the study of colonic carcinogenesis, in which the patterning of neoplastic tubules is necessary for properties of growth, invasion, and metastasis. Interestingly the nuclear expression and transcriptional activity of beta-catenin, a major oncoprotein in colonic carcinogenesis, is decisive for the first patterning of a tubule in embryogenesis, which creates the primitive gut and is called the gastrulation. Thus, basic patternings of embryogenesis and carcinogenesis might be linked. To test this hypothesis we compared morphological patterns and immunohistochemical beta-catenin stainings in colonic adenomas and adenocarcinomas with the gastrulation steps. Two analogies were found: 1) the patterning of invasion with reconstruction in adenocarcinomas corresponded to the epithelio-mesenchymal transition, ingression, and rearrangement of cells during the first phase of gastrulation; and 2) the patterning of tubular branching in adenomas and adenocarcinomas resembled the endodermal invagination during the second phase. The intratumorous distribution and intensity of nuclear beta-catenin expression was significantly correlated with the two patternings, similar to the findings in gastrulation. The results indicate microenvironmental regulations of nuclear beta-catenin expression and a return of neoplastic cells to embryonic transcriptional susceptibilities during colonic carcinogenesis.

Adenocarcinoma↗
PubMed2000

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↗
PubMed2000

Cell differentiation and matrix gene expression in mesenchymal chondrosarcomas.

Mesenchymal chondrosarcomas are small-cell malignancies named as chondrosarcomas due to the focal appearance of cartilage islands. In this study, the use of in situ detection techniques on a large series of mesenchymal chondrosarcoma specimens allowed the identification of tumor-cell differentiation pathways in these neoplasms. We were able to trace all steps of chondrogenesis within mesenchymal chondrosarcoma by using characteristic marker genes of chondrocytic development. Starting from undifferentiated cells, which were negative for vimentin and any other mesenchymal marker, a substantial portion of the cellular (undifferentiated) tumor areas showed a chondroprogenitor phenotype with an onset of expression of vimentin and collagen type IIA. Cells in the chondroid areas showed the full expression panel of mature chondrocytes including type X collagen indicating focal hypertrophic differentiation of the neoplastic chondrocytes. Finally, evidence was found for transdifferentiation of the neoplastic chondrocytes to osteoblast-like cells in areas of neoplastic bone formation. These results establish mesenchymal chondrosarcoma as the very neoplasm of differentiating premesenchymal chondroprogenitor cells. The potential of neoplastic bone formation in mesenchymal chondrosarcoma introduces a new concept of neoplastic (chondrocytic) osteogenesis in musculoskeletal malignant neoplasms, which qualifies the old dogma that neoplastic bone/osteoid formation automatically implies the diagnosis of osteosarcoma.

Apoptosis↗
PubMed2000

Sequential occurrence of primary sclerosing cholangitis and autoimmune hepatitis type III in a patient with ulcerative colitis: a follow up study over 14 years.

In 1983, a female patient born in 1963 presented with symptoms of ulcerative colitis and typical clinical and histological signs of primary sclerosing cholangitis (PSC). At this time only pANCA were positive while other marker antibodies for autoimmune liver disorders could not be detected. In summer 1987 the clinical picture changed and was replaced by laboratory and histological signs typical of autoimmune hepatitis (AIH). Thus, IgG levels increased considerably and cholestatic enzymes became normal. For the first time, anti-liver-pancreas antibodies (LP), a diagnostic marker for AIH type III could be detected. In the following years several relapses occurred also induced by repeated discontinuation of immunosuppressive therapy. Symptoms of colitis persisted but signs of cholestasis remained absent for the following ten years. In 1997, colitis exacerbated again and colectomy had to be performed together with liver transplantation. Surprisingly, histology of the explanted liver now showed the typical features of PSC stage III/IV while the significant criteria for AIH were now lacking. Thus, progression to cirrhosis was, probably, mainly induced by the biliary destructive and fibrotic process although biochemical and serological data were clearly indicative of an autoimmune, i.e. AIH-related manifestation.

Adult↗
PubMed2000

Eradication of H. pylori with pantoprazole, clarithromycin, and metronidazole in duodenal ulcer patients: a head-to-head comparison between two regimens of different duration.

BACKGROUND: The study was conducted to compare the efficacy and tolerability of two pantoprazole-based triple therapies of different length in the eradication of H. pylori. METHODS: In this double-blind, multicenter parallel group comparison, H. pylori-positive patients were randomly assigned to either the PCM-7 group (7 days of pantoprazole 40 mg bid, clarithromycin 500 mg bid, metronidazole 500 mg bid) or the PCM-14 m group (modified 14 day therapy of the same regimen with metronidazole only given for 10 days due to labeling reasons). H. pylori status was determined by urease test, histology, culture, and 13C-urea breath test. Treatment outcome was assessed 6 weeks after intake of the last study medication. RESULTS: The following eradication rates were achieved: for PCM-7 in the MITT population 83% (89/107), in the PP population 84% (81/97); for PCM-14 m in MITT 87% (92/106), in PP 88% (91/104). Ulcer healing rates were: for PCM-7 in MITT population 99% (106/107), in the PP population 99% (96/97); for PCM-14 m in MITT 99% (105/106), in PP 99% (103/104). Gastrointestinal symptoms and gastritis scores decreased in both treatment groups. Equivalence of treatment regimens could be proven for all populations. In total, 64 patients reported adverse events. Five serious adverse events occurred, all unrelated to the study medication. CONCLUSION: The two pantoprazole-based triple therapies tested in this study are equally effective in H. pylori eradication, ulcer healing and relief from ulcer pain. It is concluded that 7 days of triple therapy are generally sufficient.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Mucosal production of antigastric autoantibodies in Helicobacter pylori gastritis.

BACKGROUND: Apart form bacterial virulence factors of Helicobacter pylori, certain host factors influence the pathogenesis of H. pylori gastritis. In particular, antigastric autoantibodies that are detectable in the sera of a substantial proportion of H. pylori were shown to correlate with the development of gastric atrophy. The aim of this study was to analyze the possible antigastric autoimmune response in H. pylori gastritis at the site where the action is, i.e. , in the gastric mucosa. MATERIAL AND METHODS: Gastric biopsy specimens from antrum and corpus mucosa of 24 H. pylori-infected and of 33 noninfected patients were cultured for 3 days, and tissue culture supernatants were analyzed for the amount of locally produced IgA and IgG. Antigastric autoantibodies were screened in the sera and in the supernatants by means of immunohistochemistry. RESULTS: The infected patients had significantly higher concentrations of locally produced IgA, whereas the IgG concentrations were virtually the same in infected and noninfected patients. IgG or IgA antigastric autoantibodies, or both, were detectable only in the sera (38%) and supernatants (17%) of infected patients. Interestingly, the patient with the strongest local autoimmune response showed body-predominant H. pylori gastritis, with destruction of gastric glands and atrophy of the body mucosa. CONCLUSIONS: These results demonstrate that antigastric autoimmune reactions are detectable at the site of the disease and might be relevant for the pathogenesis of gastric mucosa atrophy in H. pylori gastritis.

Adult↗
PubMed2000

[Latent TGF-beta 1 binding protein (LTBP-1); a new marker for intra-and extraocular PEX deposits].

BACKGROUND: Pseudoexfoliation (PEX) syndrome is a generalized process of the extracellular matrix characterized by the accumulation of an abnormal pathognomonic material in various intraocular and extraocular tissues. Whereas the intraocular manifestations can be directly diagnosed by biomicroscopic observations, the extraocular manifestations can presently only be diagnosed by electron microscopic methodology. In order to better evaluate the distribution and precise localization of PEX deposits in the various organ systems, we searched for a relatively specific immunohistochemical marker for PEX material on the light microscopic level. MATERIAL AND METHODS: Eyes and tissue specimens of various organ systems (skin, heart, lungs, liver, kidney, abdominal aorta, cerebral artery, plexus choroideus, meninges) obtained from 4 organ donors with ocular PEX syndrome and age-matched control tissues were investigated by electron microscopy and immunohistochemistry using antibodies against various elastic microfibrillar components. RESULTS: Out of a panel of antibodies tested, the immunolabeling of both intra- and extraocular PEX deposits with antibodies against latent TGF-beta 1 binding protein (LTBP-1) was particularly prominent. In addition to the known intraocular sites of PEX material accumulations, focal plaque-like LTBP-1 positive deposits could be observed in the conjunctival stroma, optic nerve meninges, skin, heart muscle, lungs, kidney as well as in the adventitia of the aorta and cerebral artery from donors with PEX syndrome; such plaque-like deposits positive for LTBP-1 were not present in the control tissues. Transmission electron microscopy confirmed the presence of typical fibrillar PEX aggregates in the respective tissues. CONCLUSIONS: Antibodies against LTBP-1 provide a new and relatively specific marker for PEX deposits both in intraocular and extraocular locations. Systematic screening of PEX accumulations in a larger number of extraocular tissue specimens obtained from PEX patients may help to elucidate the functional implications and consequences of the systemic manifestations.

Aged↗