Biomedical subjects

T Kirchner

Publications and source records attributed to T Kirchner.

At least 127 records · Page 7Linked to original sources

PubMed1997

Congenital microvillous atrophy: report of two cases.

2 infants with chronic severe diarrhoea from birth and with lethal outcome have been studied. Small intestinal biopsies were examined by light and electron microscopy. Severe villous atrophy, complete loss of microvilli or rudimentary forms, intracytoplasmic vesicles, and microvillous inclusions are the characteristic features of the disease. The etiology is unknown. A disturbance in the transport of brush-border proteins to the cell surface is assumed to be the reason for congenital microvillous atrophy.

Atrophy↗

PubMed1997

Phenotypic diversity of neoplastic chondrocytes and extracellular matrix gene expression in cartilaginous neoplasms.

Chondrocyte differentiation is characterized by distinct cellular phenotypes, which can be identified by specific extracellular matrix gene expression profiles. By applying in situ analysis on the mRNA and protein level in a series of benign and malignant human chondrogenic neoplasms, we were able to identify for the first time different phenotypes of neoplastic chondrocytes in vivo: 1) mature chondrocytes, which synthesized the characteristic cartilaginous extracellular tumor matrix, 2) cells resembling hypertrophic chondrocytes of the fetal growth plate, 3) cells resembling so-called dedifferentiated chondrocytes, and 4) well differentiated chondrocytic cells, which expressed type I collagen, indicating the presence of post-hypertrophic differentiated neoplastic chondrocytes. Chondrocytes exhibiting a range of phenotypes were found to be present in the same neoplasm. The different observed phenotypes, including the dedifferentiated phenotype, were in contrast to the anaplastic cells of high-grade chondrosarcomas. Comparison of expression data with tumor morphology revealed a relationship between the cellular phenotypes, the tumor matrix composition, and the matrix and cell morphology within the neoplasms. The distinctly different phenotypes of neoplastic chondrocytes are the basis of the characteristic high biochemical and morphological heterogeneity of chondroid neoplasms and shed light on their biological and clinical behavior.

Aggrecans↗

PubMed1997

Evaluation of the antiinflammatory activity of a dual cyclooxygenase-2 selective/5-lipoxygenase inhibitor, RWJ 63556, in a canine model of inflammation.

Sterile perforated polyethylene spheres (wiffle golf balls) were implanted s.c. in beagle dogs. A local inflammatory reaction was elicited within the spheres by injecting carrageenan. Changes in leukocyte count, prostaglandin E2, thromboxane B2 and leukotriene B4 levels were monitored in fluid samples collected over a 24-hr period. Blood samples were also collected at various time points and analyzed for prostaglandin E2 and leukotriene B4 production after ex vivo calcium ionophore treatment. Effects of standard antiinflammatory agents (aspirin, indomethacin, dexamethasone, tenidap and zileuton) and newer cyclooxygenase-2 (COX-2) selective agents (nimesulide, nabumetone and SC-58125) were determined after oral administration. Ex vivo inhibition of cyclooxygenase product synthesis (prostaglandin E2, thromboxane B2) in whole blood was used as an indicator of activity for the constitutive COX-1 isoform, although inhibition of the synthesis of these mediators in the chamber exudate during an inflammatory process is believed to represent COX-2 inhibition. Treatment effects on leukotriene B4 production were also determined both ex vivo in whole blood and in the fluid. All of the compounds tested, except aspirin, inhibited leukocyte infiltration into the fluid exudate. Inhibitors that exert their effects on both isozymes of cyclooxygenase attenuate production of cyclooxygenase metabolites in both the inflammatory exudate and in peripheral blood ex vivo, although COX-2 selective inhibitors only demonstrated activity in the exudate. A 5-lipoxygenase inhibitor (zileuton), a corticosteroid (dexamethasone) and a dual COX-2 selective/5-lipoxygenase inhibitor (RWJ 63556) had similar profiles in that they all inhibited cell infiltration and eicosanoid production in the fluid and also attenuated leukotriene B4 production in both the fluid and blood.

Animals↗

PubMed1997

[Adrenal gland incidentaloma is not a "time bomb"--arguments for follow-up control].

Adrenal masses are nowadays more and more diagnosed incidentally. In the vast majority of cases these "incidentalomas" are benign adrenocortical adenomas which do not compel operative therapy. In about 12% of patients an endocrine activity is detected. With Increasing tumor size the risk of malignancy increases. This article summarizes recommendations, only to allow patients with endocrine activity or an increased risk of malignancy to be selected for surgery. A small uncertainty will always remain, but may be minimized by an individually tailored follow-up.

Adrenal Gland Neoplasms↗

PubMed1997

[Regional cooperation in molecular biology topics].

Research on rare events, such as the occurrence of port-site metastases, can be speeded up by pooling patients from different hospitals. Multidisciplinary approaches, involving surgeons, pathologists and molecular biologists, allow more detailed experimental results to be obtained. Research costs are kept low by using existing infrastructures over a short period of time.

Cost-Benefit Analysis↗

PubMed1997

[Phenotypic analysis in colorectal carcinoma: an international interdisciplinary project].

An European research network grouping surgeons, pathologists, biochemists and molecular biologists is presented. The aim of this network is to define new diagnostic, prognostic and therapeutic markers at protein and RNA levels in colorectal cancer. The methodology is based on specific sample preparation techniques, allowing the isolation of pure epithelial cells, and on differential-display techniques, such as two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and reverse arbitrarily-primed polymerase chain reaction (RAP-PCR).

Biomarkers, Tumor↗

PubMed1996

[Pathology of Helicobacter infection].

The colonization of gastric mucosa by Helicobacter pylori (H.p.) is a special form of chronic bacterial infection characterized by long term persistence of microbes because cause of an inefficiency of local immune responses. The resulting chronic gastritis causes decisive transformations of gastric mucosa. They comprise the acquisition of an active mucosa-associated lymphoid tissue as well as the development of glandular atrophy and intestinal metaplasia in the stomach. Both transformations change normal gastric functions, and create abnormal microenvironments with an increased risk for gastric cancer and lymphoma. Own recent investigations indicate, that the distribution and severity of chronic gastritis might be decisively influenced by a rise of antigastric autoimmune reactivity during the H.p. infection. The histologic examination of gastric biopsy samples is essential for an exact diagnosis of the complex pathogenic processes in chronic gastritis. In the future special emphasis of histologic analyses has to be put on the subtypes of gastritis, which are prone for complications and on the evaluation of gastritis remission after H.p. eradication.

Autoimmunity↗

PubMed1996

A Herpes saimiri oncogene causing peripheral T-cell lymphoma in transgenic mice.

Herpesvirus saimiri is an oncogenic virus causing rapid T-cell lymphomas in New World primates and rabbits. Deletion analysis of one strain of H saimiri has indicated an open reading frame, StpA, necessary for oncongenicity in monkeys. We have investigated the function of StpA in tumor induction by the generation of transgenic mice. Expression of two different constructs caused the development of peripheral lymphomas. The infiltrating cells were of T-cell origin, expressing mainly the CD4 phenotype and restricted sets of V beta chains. Thus, StpA is not only necessary for the oncogenicity of Herpesvirus saimiri, but is also sufficient for the induction of peripheral pleomorphic T-cell lymphomas.

Animals↗

PubMed1996

Antigastric autoantibodies in Helicobacter pylori gastritis: prevalence, in-situ binding sites and clues for clinical relevance.

Colonization of human gastric mucosa with Helicobacter pylori leads to chronic active gastritis and induces the occurrence of an acquired mucosa-associated lymphoid tissue (MALT) in the stomach. This remodelling of the gastric mucosa together with chronic antigen persistence may induce autoimmune reactions. The aim of this study was to investigate humoral autoimmune reactions to human gastric mucosa in H. pylori gastritis and their clinical relevance. Sera from patients with dyspeptic symptoms were tested for presence of IgG immunoglobulins against H. pylori. Gastric infection with H. pylori and alterations of gastric mucosa were demonstrated by histological examination of gastric biopsy specimens. All sera were tested for reactivity against human gastric mucosa by immunohistochemistry. Two different in-situ binding sites of antigastric autoantibodies were observed. Binding to canalicular structures within parietal cells was significantly correlated with antibodies to H. pylori, elevated basal gastrin levels and atrophy of gastric corpus glands. Our data indicate that autoimmune reactions to antigens in the human gastric mucosa occur in H. pylori gastritis and that they may play a role in the pathogenesis of the disease.

Adult↗

PubMed1996

Reactivation by various oximes of human erythrocyte acetylcholinesterase inhibited by different organophosphorus compounds.

The new bispyridinium oximes HI 6 and HLö 7 are promising antidotes against poisoning by highly toxic organophosphorus compounds, i.e. nerve agents. Until now, their ability to reactivate pesticide inhibited human acetylcholinesterase (AChE) has not been elucidated. For this purpose human erythrocyte AChE (EC 3.1.1.7) was inhibited (30 min) by chlorfenvinphos, dichlorvos, dicrotophos, heptenophos, mevinphos, monocrotophos, paraoxon, phosphamidon, trichlorfon, malaoxon, omethoate, oxydemeton-methyl or methamidophos by 85-98% of control. After removal of excess inhibitor, obidoxime, pralidoxime (2-PAM), HI 6 or HLö 7 (10, 30 or 100 mumol/l) were added and the AChE activity was measured spectrophotometrically at various times thereafter (5-60 min). The oximes significantly, but not completely, reactivated organophosphate inhibited AChE. The velocity and extent of reactivation were dependent on the oxime and its concentration. In all cases obidoxime was superior to the three other oximes, followed by HLö 7, 2-PAM and HI 6. In most cases obidoxime and HLö 7 were most effective at 10 or 30 mumol/l while 2-PAM and HI 6 needed 100 mumol/l. These data suggest that 2-PAM HI 6 and HLö 7 are less patent than obidoxime in reactivating human AChE inhibited by organophosphate pesticides.

Acetylcholinesterase↗

PubMed1996

An immuno-electron-microscopic study of human thymic B cells.

Thymic B cells are a constituent of normal human thymic medulla. They are supposed to play a role in T cell maturation. Thymic B cells have been characterized morphologically and immunohistochemically at the light-microscopic level. Their ultrastructural appearance in vivo has not been demonstrated. Six normal infantile thymi were immunolabelled with the pan-B cell marker CD20 using a pre-embedding technique and viewed at the electron-microscopic level. Cells expressing CD20 had long cytoplasmic processes. They were all "asteroid" in shape and in close contact with thymocytes. Also, their long cytoplasmic processes intermingled with cytoplasmic processes of cells that were presumed to be interdigitating reticulum cells (IDC) based on morphological criteria. Thymic B cells may act in concert with IDC during T cell maturation.

Antigens, CD20↗

PubMed1996

Chondrocytic cell differentiation in clear cell chondrosarcoma.

Clear cell chondrosarcoma is a rare mesenchymal neoplasm of unclear differentiation. Besides having a chondrogenic nature, an osteogenic differentiation was also proposed. In this study, expression analysis of extracellular matrix genes, which are specific for different mesenchymal cell differentiation pathways, were used to get a better understanding of origin and differentiation pattern of the clear cell chondrosarcoma tumor cells. Our in situ analysis of two cases shows that (1) chondrocytic cell differentiation as marked by the expression of cartilage collagen type II and proteoglycans is a characteristic feature within the development of the neoplasm, (2) multifocal chondrocyte hypertrophy as shown by the expression of type X collagen does occur, and (3) no significant expression of collagen type I, the main gene product of osteoblastic cells, is found by the neoplastic cells. Thus, our study indicates that clear cell chondrosarcoma shows a chondrogenic, but not osteogenic, differentiation and represents a true chondrosarcoma. The unusual scarcity of its extracellular and the multifocal expression of type X collagen marks clear cell chondrosarcoma as a chondrosarcoma tumor entity of a particular cell differentiation pattern. The expression of cartilage type collagens represents a distinct marker from bone metastases of clear cell neoplasms of other origins.

Adult↗

PubMed1996

Occurrence of multiple lymphoepithelioma-like carcinomas and MALT-type lymphoma in the stomach: detection of EBV in carcinomas but not in lymphoma.

A multifocal lymphoepithelioma-like carcinoma and a low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT-type) were found simultaneously in the stomach of a 65-year-old patient. Carcinoma and lymphoma were intimately associated forming complexes resembling lymphoepithelial lesions at the primary gastric site and in lymph node metastases. The two tumours had developed on a background of severe chronic-atrophic gastritis of the mucosa of antrum and fundus. Autoantibodies to normal gastric glandular tissue could be demonstrated in the patient's sera. Using non-radioactive in situ hybridization (ISH), Epstein-Barr virus (EBV) sequences were detected in virtually all carcinoma cells but neither in the non-neoplastic mucosa nor in the lymphoma. These findings suggest that a focal EBV infection occurred early in the development of the carcinoma followed by a subsequent clonal expansion of the EBV-containing tumour cells. A neoplastic transformation in MALT-type lymphoma is not EBV-related but might be triggered by altered immune mechanisms.

Aged↗

PubMed1996

Characterization of lymphocytic infiltrates in Helicobacter pylori-associated gastritis.

BACKGROUND: This study evaluated the specific subset composition of lymphocytes present in Helicobacter pylori-associated gastritis (HAG), since reports so far have led to inconclusive and conflicting results. METHODS: Endoscopic biopsy specimens from 56 patients were studied by quantitative immunohistochemistry using monoclonal antibodies against the lymphocyte markers CD3, CD22, CD4, CD8, CD45RO, CD1O3, TCR alpha/beta, and TCR gamma/delta. Lamina propria and intraepithelial compartments were evaluated separately. Grade, activity, and density of bacterial colonisation were assessed histologically and with Warthin-Starry stain. RESULTS: Evaluation showed a significant increase in CD4+, CD45RO+, TCR alpha/beta+ activated lamina propria lymphocytes in HAG which correlated with grade and activity of gastritis and degree of bacterial colonisation, whereas subsets of intraepithelial lymphocytes did not change significantly. TCR gamma/delta+ T cells were not found to be increased in HAG. CONCLUSIONS: Selective expansion of CD4+, CD45RO+ memory-type T cells could reflect an antigen-specific and/or chemokine-mediated effect in HAG. Locally produced CC chemokines such as RANTES have been detected in HAG.

Adult↗

PubMed1996

Expression of neurofilaments and of a titin epitope in thymic epithelial tumors. Implications for the pathogenesis of myasthenia gravis.

Autoantibodies against both striated muscle proteins, particularly titin, and the acetylcholine receptor are a hallmark of thymoma-associated myasthenia gravis. However, the stimulus for these responses remains enigmatic as whole titin is not detectable in these tumors. This study reports that in thymomas with cortical differentiation many of the neoplastic epithelial cells expressed low and medium molecular weight neurofilaments detected with several antibodies (on selections and blots) and at the RNA level (by reverse transcriptase polymerase chain reaction). Moreover, higher molecular weight forms sharing at least one epitope with titin were detectable slightly less frequently, as were the more strongly phosphorylated epitopes. In stark contrast, in medullary and mixed thymomas, and especially in the normal thymus, immunoreactivity with anti-neurofilament antibodies was rare. This aberrant overexpression of a titin epitope by epithelial cells with antigen-presenting phenotype in an inappropriate cortical microenvironment suggests that they might autosensitize maturing T cells there and so initiate anti-titin autoimmunity in these patients.

Adolescent↗

PubMed1996

Three siblings with Walker-Warburg Syndrome.

The Walker-Warburg syndrome (WWS) is an autosomal recessive disease entity within the framework of "cerebro-ocular-muscular syndromes". The gene locus is still undetected. Its diagnostic criteria have been firmly established in the literature on newborns or infants affected with the disease. However, a diagnosis of severe pathologic conditions must often be made on the basis of ultrasound examination at a fetal age. It is therefore necessary to examined whether the diagnostic criteria are sufficient to warrant a diagnosis at the fetal stage. We here report on a new family affected with WWS. Two elder siblings had presented with epileptic seizures, eye abnormalities as well as multiple skeletal dysplasias (the latter finding in the first child only) in the neonatal period, and died in their first years. Postmortem examination of the second child revealed type II lissencephaly, buphthalmos, and undifferentiated retina with rigid retinal folds. Skeletal muscle tissue was not examined. In a sibling fetus, bilateral cataract was detected in the 17th gestational week by ultrasonographic examination. Postmortem examination in the 23rd gestational week revealed type II lissencephaly and bilateral cataract. Skeletal muscle was normal. Taken together, all siblings were diagnosed as Walker-Warburg syndrome. In the fetal case, prenatal diagnosis could only be made with confidence against a background of a positive family history.

Abnormalities, Multiple↗

PubMed1996

[Relevance of antigastric autoantibodies in Helicobacter pylori gastritis].

We have recently shown that antigastric autoantibodies occur in a considerable number of Helicobacter pylori (H. pylori) infected patients. Particularly, autoantibodies to canaliculi within parietal cells of human gastric body mucosa are strongly associated with H. pylori gastritis. In this study we analyzed the implications of this type of autoantibody for histological and for clinical parameters of the disease. 126 patients with upper abdominal complaints were included in our study. Several histological and clinical parameters were evaluated. Presence of anticanalicular autoantibodies is significantly correlated with a higher degree of gastritis in the body mucosa, with atrophic changes in the gastric mucosa, with elevated fasting gastrin levels and a decreased pepsinogen I/pepsinogen II ratio. These data indicate, that the host's autoimmune response to canaliculi of parietal cells is of relevance for the pathogenesis and outcome of H. pylori gastritis.

Atrophy↗

PubMed1996

[Apoptosis in chronic gastritis: correlation of glandular apoptosis with antigastric autoantibodies].

In the course of time, chronic gastritis results in gastric atrophy. A typical example is type A-gastritis. Parietal cell antibodies lead to a loss of glands in the corpus mucosa. Atrophy is preceded by a preatrophic state (active type A-gastritis). Recently, gastric autoantibodies could also be detected in Helicobacter pylori induced type B-gastritis and could be specified as canalicular and luminal antibodies. The question of this study was whether apoptosis is responsible for the loss of gastric epithelium. Gastric biopsies from normal mucosa, type B-gastritis and active type A-gastritis were analysed for the presence of apoptosis using the TUNEL-method. Type B-gastritis was subdivided in cases without autoantibodies, with canalicular and luminal autoantibodies and with both types. In each case antrum- and corpus-mucosa was available and 200 cells of the foveolar as well as of the glands were counted. Normal mucosa showed only few apoptotic cells. The number of apoptosis was significantly elevated in all cases of type B-gastritis in the whole antrum and in the foveolar epithelium of the corpus. Active type A-gastritis revealed the highest number of apoptosis in the gastric glands of corpus mucosa. Subdividing type B-gastritis the most interesting result was the cases with canalicular antibodies had a similar high number of apoptosis in the corpus glands as active type A-gastritis. These cases were in this regard significantly different from cases of type B-gastritis without autoantibodies. The findings suggest that gastric atrophy might be the result of apoptosis in the gastric epithelium and that, possibly, different types of type B-gastritis lead to atrophy in different regions of the stomach.

Adolescent↗