Biomedical subjects

T Kirchner

Publications and source records attributed to T Kirchner.

At least 37 records · Page 2Linked to original sources

PubMed2001

Spin-resolved NEXAFS from resonant X-ray scattering (RXS).

Resonantly excited metal K core line spectra of NiO, MnO, CoO and other compounds have been investigated at the beamlines X21 (NSLS/BNL), BW1 and W1.1 (HASYLAB/DESY). From analysis of spectral data we have drawn the following conclusions: -spin conservation is valid in the scattering process, for excitations below the absorption threshold as well as above it, -the absorption thresholds are different for spin-up and spin-down components of resonantly scattered spectra, -quadrupole transitions are very important or even crucial in the excitation process. Provided that these conclusions are true, a novel technique for quantitative resolution of NEXAFS spectra into spin-up and spin-down components has been developed. Since the method employs spin conservation and local spin references, it needs no circularly polarized radiation and no sample magnetization for taking both the RXS and NEXAFS spectra. Hence antiferromagnetic and paramagnetic materials can be investigated as well. Utilizing linear dichroism by angular-dependent measurements on single-crystal samples additional resolution of NEXAFS spectra is possible with respect to the orbital symmetry. Application of the method to paramagnetic MnO, for the first time, provides new and unambiguous experimental results confirming modern (LSDA+U) calculations: The metal K pre-edge XAS of MnO has predominantly 3d(t2g and eg) spin-down character. On the other hand, the delocalized p-like states, arising from the p-d band effect hybridization have spin-up character.

Journal Article↗

PubMed2001

Linear dichroism in 3d transition metal NEXAFS of correlated materials.

Investigations of 3d transition metal (TM) compounds by means of linear dichroism in TM K-NEXAFS will be reported. At this, the decomposition of the angular-dependent NEXAFS into orbital projected components are important problems. A survey is given on methods how to extract information on the geometrical, electronic and magnetic structure from linearly polarized NEXAFS and EXAFS spectra. New results on CuO and CuPc (Copper Phthalocyanine) are reported. A reference is given to the novel method for spin-resolving of NEXAFS by analysis of resonantly scattered X-ray core lines.

Journal Article↗

PubMed2001

Polarized Cu K edge XANES spectra of CuO--theory and experiment.

Polarized Cu K edge x-ray absorption near-edge structure (XANES) spectra of CuO are analyzed. Partial spectral components reflecting both dipole and quadrupole transitions are resolved from the experiment. Theoretical spectra were obtained using the real-space multiple-scattering technique and by calculating the band structure via the pseudopotential method. We demonstrate that the pre-peak is of a quadrupole character and find its decomposition into individual d components. The self consistent pseudopotential calculation, free from any constraints on the form of the potential, improves the agreement between theory and experiment in those areas where real-space calculation, based on non-self-consistent muffin-tin potential, fails. Therefore we argue that the most significant contributions to the Cu K edge XANES come from one-electron processes.

Journal Article↗

PubMed2001

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↗

PubMed2001

Apoptotic cell death is not a widespread phenomenon in normal aging and osteoarthritis human articular knee cartilage: a study of proliferation, programmed cell death (apoptosis), and viability of chondrocytes in normal and osteoarthritic human knee cartilage.

OBJECTIVE: Chondrocytes are crucial for adequate matrix balance and function. Cell proliferation and, recently, extensive apoptotic cell death have been reported in osteoarthritic (OA) cartilage. Apoptotic cell death would be an obvious central factor in the initiation and progression of OA, since there is no potential for replacing articular chondrocytes in the adult. Therefore, we studied the occurrence of apoptotic cell disintegration and cell proliferation in OA and normal articular cartilage obtained from the knees of adult donors of all ages. METHODS: Following immunostaining for cellular proteins as well as staining for nuclear DNA, we performed triple-channel confocal laser scanning microscopy on thick cartilage slices to evaluate lacunar emptying and cell viability. Cell proliferation and apoptotic cell death were evaluated morphologically, by immunodetection of the proliferation-associated Ki-67 antigen, and by the TUNEL reaction. RESULTS: With the exception of the calcified layer, we were not able to detect any major (apoptotic or nonapoptotic) cell disintegration in normal young or aged articular knee cartilage. Single apoptotic cells were detected in OA articular knee cartilage. A significant increase in lacunar emptying was observed in late-stage specimens with higher Mankin scores compared with age-matched normal control cartilage specimens, but not in low-grade lesions. A significant (but lesser) increase in empty lacunae was also observed with age in normal cartilage. Cell proliferation was rarely detected in OA cartilage samples and was not detected at all in normal cartilage samples. CONCLUSION: Our results confirm the findings of previous studies showing that cell proliferation occurs in OA cartilage. They also show that, contrary to previous suggestions, apoptotic cell death is not a widespread phenomenon in aging or OA cartilage.

Adult↗

PubMed2001

[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↗

PubMed2001

[Diagnosis of celiac disease and sprue. Recommendations of the German Society for Pathology Task Force on Gastroenterologic Pathology].

The diagnosis of celiac disease (CD) is based upon histological findings in duodenal or jejunal biopsy specimens. In recent years it has been seen 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; 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 intraepithelial lymphocytes counts. Exact histological classification of the histological findings is required for diagnostic purposes and for monitoring of CD patients. This has become possible by using a modified Marsh classification. We present both the histological presentation of CD and the modified Marsh classification, and the most important differential diagnoses.

Biopsy↗

PubMed2001

Tenascin: a sensitive and specific diagnostic marker of minimal collagenous colitis.

Collagenous colitis is a rare cause of chronic watery diarrhea. In this condition, endoscopic findings are usually normal. Currently, the diagnosis relies on the histological presence of thick subepithelial bands of collagen deposits and an inflammatory infiltrate within the mucosa. However, these subepithelial bands may be developed only focally and may be too subtle to allow a definitive diagnosis upon routine hematoxylin and eosin (HE) and van Gieson's stainings. Recently, we and others were able to show a prominent staining of tenascin and type-VI collagen in the subepithelial band-like structures. In this study, we tested the diagnostic value of tenascin staining and type-VI collagen immunolocalization for the identification of collagenous colitis and compared it with conventional histology and histochemical detection of collagens. The analysis was based on 434 biopsy specimens of collagenous colitis, other forms of colitis, and normal mucosa. We were able to show that the immunohistochemical detection of increased amounts of tenascin, selectively in the subepithelial zone, is a specific test for collagenous colitis, with a sensitivity superior to conventional histological and histochemical detection, especially in minimal collagenous colitis (P<0.001). Of note, tenascin staining also allows the diagnosis of collagenous colitis in biopsies obtained only from the rectum and sigmoid colon, thus avoiding the need for colonoscopic investigations. Tenascin immunostaining is a simple and safe tool to complement conventional histological diagnostics in clinically and histopathologically unclear cases of diarrhea.

Adolescent↗

PubMed2001

Metaplasia, intraepithelial neoplasia and early cancer of the stomach are related to dedifferentiated epithelial cells defined by cytokeratin-7 expression in gastritis.

Cancer presumably arises from stem cells, preserved in an undifferentiated status since fetal development, or from a dedifferentiation of mature cells that return into a fetal phenotype with the potential for proliferation and renewal. Dedifferentiation in this context could represent a transient phase, passed through by cells, before they switch to redifferentiation, metaplasia or neoplasia. Cytokeratin-7 (CK7) is present in fetal, largely absent in normal adult, and transiently neoexpressed in metaplastic and neoplastic epithelial cells of the stomach according to previous observations. CK7 neoexpression in the stomach could, hence, define a fetal-like, dedifferentiated, cellular phenotype during the development of metaplasia and neoplasia. To test this hypothesis, we investigated CK7 expressions in fetal stomachs, non-neoplastic control stomachs, and neoplastic stomachs exhibiting metaplasia, intraepithelial neoplasia, and early cancer. Proliferation and beta-catenin expression of CK7-positive cells were also evaluated. The chronology of CK7 expression was studied during the experimental gastritis-cancer sequence in Mongolian gerbils. Our results show that metaplastic and neoplastic changes in the gastritis-cancer sequence are related to dedifferentiated epithelial cells which are defined by CK7 expression and can phenotypically be linked to fetal cells at the start of gastric pit development. The dedifferentiated cells exhibit a low proliferation and beta-catenin accumulation, similar to stem cells. Thus, the "stem cell" and "dedifferentiation" hypotheses for cancer origin could complement one another, and dedifferentiation-redifferentiation processes might be decisive for carcinogenesis in the stomach.

Adenocarcinoma↗

PubMed2001

The invasion front of human colorectal adenocarcinomas shows co-localization of nuclear beta-catenin, cyclin D1, and p16INK4A and is a region of low proliferation.

At the invasion front of well-differentiated colorectal adenocarcinomas, the oncogene beta-catenin is found in the nuclear compartment of tumor cells. Under these conditions, beta-catenin can function as a transcription factor and thus activate target genes. One of these target genes, cyclin D1, is known to induce proliferation. However, invasion front of well-differentiated colorectal adenocarcinomas are known to be zones of low proliferation and express the cell cycle inhibitor p16INK4A. Therefore, we investigated the expression profiles of nuclear beta-catenin, cyclin D1, p16INK4A, and the Ki-67 antigen, a marker for proliferation, in serial sections of well-differentiated colorectal adenocarcinomas. Invasion fronts with nuclear beta-catenin were compared with areas from central parts of the tumors without nuclear beta-catenin, for the expression of cyclin D1, p16INK4A, and Ki-67. It was observed that expression of nuclear beta-catenin, cyclin D1, and p16INK4A at the invasion front are significantly correlated. Such areas exhibit low Ki-67 expression indicating a low rate of proliferation. Thus, in colorectal carcinogenesis the function of beta-catenin and its target gene cyclin D1 does not appear to be the induction of tumor cell proliferation. In particular, the function of cyclin D1 should be reconsidered in view of these observations.

Adenocarcinoma↗

PubMed2001

Matrix gene expression analysis and cellular phenotyping in chordoma reveals focal differentiation pattern of neoplastic cells mimicking nucleus pulposus development.

Chordoma is the fourth most common malignant primary neoplasm of the skeleton and almost the only one showing a real epithelial phenotype. Besides classic chordoma, so-called chondroid chordoma was described as a specific entity showing cartilage-like tissue within chordomatoid structures. However, since its first description, strongly conflicting results have been reported about the existence of chondroid chordoma and several studies suggested chondroid chordomas being in fact low-grade conventional chondrosarcomas. In the present study, we used cytoprotein expression profiling and molecular in situ localization techniques of marker gene products indicative of developmental phenotypes of chondrocytes to elucidate origin and biology of chondroid chordoma. We were able to demonstrate the chondrogenic potential of chordomas irrespectively of the appearance of overt cartilage formation by identifying the multifocal expression of type II collagen, the main marker of chondrocytic differentiation. Additionally, the cartilage-typical large aggregating proteoglycan aggrecan was present throughout all chordomas and, thus, a very characteristic gene product and marker of these neoplasms. Biochemical matrix composition and cell differentiation pattern analysis showed a high resemblance of classic chordomas and in chordoid areas of chondroid chordomas to the fetal chorda dorsalis, whereas chondroid areas of chondroid chordomas showed features similar to adult nucleus pulposus. This demonstrates on the cell function level the chondrocytic differentiation potential of neoplastic chordoid cells as a characteristic facet of chordomas, mimicking fetal vertebral development, ie, the transition of the chorda dorsalis to the nucleus pulposus. Our study firmly establishes a focal real chondrocytic phenotype of neoplastic cells in chordomas. Chondroid chordoma is neither a low-grade chondrosarcoma nor a misnomer as discussed previously.

Aggrecans↗

PubMed2001

Isolation of RNA from small human articular cartilage specimens allows quantification of mRNA expression levels in local articular cartilage defects.

Human adult cartilage is an inherently difficult tissue from which to isolate RNA. The RNA isolation techniques described so far have generally only been successfully applied to the isolation of RNA from larger amounts of cartilage. However, it is important to be able to analyse focal cartilage lesions in order to understand the local processes in the cartilage degeneration process. Therefore, we have developed a protocol for isolating RNA directly from as little as 10 mg wet weight of cartilage followed by quantitative PCR analysis. We were able to analyse the expression levels of several genes in parallel including aggrecan and type II collagen.

Aggrecans↗

PubMed2001

Transcription of cytokeratins 8, 18, and 19 in bone marrow and limited expression of cytokeratins 7 and 20 by carcinoma cells: inherent limitations for RT-PCR in the detection of isolated tumor cells.

The suitability of "real-time" quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for the detection of isolated carcinoma cells in bone marrow was investigated by evaluating the expression of cytokeratin (CK)7, CK8, CK18, CK19, and CK20 in 17 gastrointestinal cancer cell lines, 64 control bone marrow specimens from noncancer patients, and 30 bone marrow specimens from patients with gastric or colorectal cancer. RT-PCR products for CK8 and CK18 were detected in all cancer cell lines, but only 16, 5, and 11 cell lines provided evidence for CK19, CK7, and CK20 transcription. Variable numbers of bone marrow specimens from noncancer patients demonstrated background transcription of CK8 (78.1%), CK18 (95.3%), CK19 (35.9%), CK20 (29.6%), and CK7 (16.7%). Maximal background transcription for CK8, CK18, and CK19 ranged from 52.2 to 56.1 copies/10(3) copies glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the corresponding values of 0.06 and 0.76 copies for CK7 and CK20 being distinctly lower. When maximal background values were used as a threshold value to define positivity in tumor cell dilution experiments, sensitivity levels of one tumor cell in 10(4) bone marrow cells were determined for CK7 and CK20 RT-PCR assays. Maximal background expression values of the different CKs as obtained in the control series were exceeded once (CK20), twice (CK18 and CK19), and 18 times (CK7) in bone marrow specimens from cancer patients, with none of these specimens exceeding the maximal background expression value of CK8. We conclude that RT-PCR for CK8, CK18, and CK19 cannot be recommended for the detection of isolated tumor cells in bone marrow of cancer patients. On the other side, the limited number of gastric and colorectal cancer cell lines expressing CK7 and CK20 indicates that assay sensitivity for these CKs might be limited because of their selective expression by carcinoma cells.

Animals↗

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

Right-sided shift found in metachronous colorectal adenomas.

BACKGROUND AND STUDY AIMS: Patients who have had a colorectal adenoma are likely to develop a metachronous adenoma, and therefore need to be kept under surveillance. The question is whether metachronous adenomas will be found at the same anatomical site as the preceding adenomas, thus prompting us to focus surveillance examinations on this region, using flexible sigmoidoscopy or total colonoscopy. PATIENTS AND METHODS: Between 1978 and 1996 a long-term follow up of 1091 patients was prospectively documented at the Erlangen Registry of Colorectal Polyps. The anatomical sites--distal (rectosigmoid) and proximal colon--of two subsequent generations of metachronous adenomas were analysed using logistic regression analysis. RESULTS: In 556 (51%) patients metachronous adenomas were found during follow up. In 211 (37.9%) of these patients a right-sided shift in the first generation of metachronous adenomas in comparison with initial lesions (P<0.0001) was found. Some 305 patients underwent further follow up, and 51 (27.1%) out of 188 patients with metachronous lesions demonstrated a right-sided shift in their second generation (vs. first generation) of metachronous adenomas. Proximally located first generation metachronous adenomas would be missed by flexible sigmoidoscopy in 50.8% of patients with only distal adenomas at baseline colonoscopy, and in 58.7% of patients with second-generation lesions. Multivariate analysis revealed that multiplicity (odds ratio 2.64, 95% CI 1.49-4.66) and size of initial adenomas (>5 mm) (odds ratio 3.60, 95% CI 1.96-6.66) were significantly associated with a right-sided shift in metachronous adenomas, while female gender was associated with a significantly lower tendency to manifest a right-sided shift (odds ratio of 0.64. 95% CI 0.43-0.94). CONCLUSIONS: Metachronous adenomas are found significantly more often in the right colon than would be expected assuming clustering at the same anatomical site as the preceding lesions. Total colonoscopy is thus needed for surveillance, regardless of the initial adenoma site.

Adenoma↗

PubMed2001

Tip60 is a cell-type-specific transcriptional regulator.

Tip60 was originally identified as cellular HIV-Tat interacting protein and has been shown to augment Tat-dependent transcription. It has also been shown to interact with various cellular transcription factors and to belong to the nuclear histone acetyltransferase (HAT) family. To further elucidate the function of Tip60 and its HAT domain in transcription regulation, we compared Tip60 activity in HeLa and Jurkat T lymphoma cells. Here we show that Tip60 augments the HIV-1 Tat activity at the HIV-LTR promoter in HeLa but inhibits it in Jurkat cells. Moreover, we isolated two new variants of the Tip60 protein (Tip60Delta1, Tip60Delta2) from Jurkat cells. The Tip60Delta2 variant lacks the entire HAT domain but modulates HIV-1 Tat activity like full-length Tip60. In addition, Tip60 and the transcriptional repressor ZEB (zinc finger E box binding protein) interact specifically in the yeast two-hybrid system and additively inhibit the CD4 enhancer/promoter activity in Jurkat cells. Thus, Tip60 may function as corepressor of the ZEB protein. In summary, these data show that Tip60 functions as a cell-type-specific transcriptional regulator and that the HAT domain is not required for either transcriptional activation or inhibition. This indicates that Tip60 may function by recruiting additional cell-type-specific cofactors.

Acetyltransferases↗

PubMed2001

Cell biology and matrix biochemistry of chondromyxoid fibroma.

We studied matrix composition and gene expression pattern in chondromyxoid fibromas on the protein and the messenger RNA levels. We could clearly identify focal chondrocytic differentiation within chondromyxoid fibroma by the expression and deposition of type II collagen, which is a marker of chondrocytic cell differentiation. We also were able to show expression of collagen types I, III, and VI in the neoplasm. The major tumor portion was, however, characterized by the presence of hydrated proteoglycans and only minor amounts of collagens, a matrix composition responsible for the myxoid matrix appearance of most parts of these neoplasms. By analyzing cytoprotein expression, we found S-100 protein restricted to cells of the chondroid areas, suggesting S-100 protein staining to be of little help as a positive diagnostic marker for chondromyxoid fibroma. Our data show a specific matrix composition of chondromyxoid fibroma, not previously found in other mesenchymal neoplasms, including chondroblastoma, osteochondroma, enchondroma, and chondrosarcoma. This justifies chondromyxoid fibroma as a specific neoplastic entity, both clinically and biologically.

Adolescent↗

PubMed2001

[A new Approbation Order for teaching medical pathology].

A basic reform and a draft of a new approbation order were developed during the last years to improve medical education in Germany. Aims of this reform are to link the theoretical and practical teaching, to foster the interdisciplinary teaching, to promote case- and problem-based instruction, to reduce written multiple choice examinations, and to promote oral exams. During the discussion about the reform proposals were made to put much more weight on the social and psychological aspects of health care and to reduce the teaching of a science-based understanding of disease, for which pathology stands. In the final draft of the reform, however, pathology was maintained as subject of clinical education. Decisive changes now include, that the traditional distinction between general and special pathology will be abolished, and that a case- and problem-based teaching by interdisciplinary clinical-pathological conferences will be fostered. Thus the education will consist of a systematic lecture and practical sessions in pathology, which have to focus on the basic principles of the etiology, pathogenesis and classification of human diseases. Practical clinical aspects of pathology will then be thought by problem-based and interdisciplinary clinical pathological conferences or demonstrations, which start in the 4th year of the curriculum and have to be continued during the practical year's term until the end of the studies. Presently the new approbation order still requires consent of the Bundesrat. It depends on agreement about the limitation for the maximum number of students, the regulation of admittance to the medical education and the cost effects of the reform. There are some indications that solutions of these problems might be achieved during 2001.

Education, Medical↗