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T Kirchner

Publications and source records attributed to T Kirchner.

At least 145 records · Page 8Linked to original sources
PubMed1996

[Molecular mimicry between neurofilaments and titin as the basis for autoimmunity towards skeletal muscle in paraneoplastic myasthenia gravis].

AIMS AND METHODS: Autoantibodies against striated muscle proteins, particularly titin, characteristically distinguish thymoma-associated from non-paraneoplastic myasthenia gravis (MG) patients. However, the stimulus for this autoimmunity remains enigmatic since whole titin is not detectable in these tumors. Since Neurofilaments (NF) contain titin epitopes, MG-associated thymomas were investigated for NF expression using immunohistochemistry and Western blotting. RESULTS: In thymomas with cortical differentiation many of the neoplastic epithelial cells expressed medium molecular weight NF at the protein level. In sharp contrast, in medullary and mixed thymomas and in normal thymuses immunoreactivity with anti-NF antibodies was rare. CONCLUSION: The overexpression of NFs with titin epitopes by neoplastic cells in an inappropriate cortical environment may be the basis for the autosensitization of developing T-cells against titin in MG-associated cortical type thymomas.

Autoantibodies↗
PubMed1996

[Inflammatory cytokine mediated anti-anabolic effects: a potential mechanism in rheumatoid cartilage degeneration].

Increased levels of inflammatory cytokines such as II-1 and TNF-alpha are described in rheumatoid and osteoarthritic synovial fluid. These mediators are also very well established anti-anabolic modulators of chondrocyte synthetic activity in vitro. Our study aimed to investigate, whether chondrocytes in rheumatoid and osteoarthritic cartilage in situ show reaction pattern compatible with the putative effects of these modulatory agents. Immunohistochemical analysis using type II collagen specific antibodies showed considerable loss of staining in many sites of osteoarthritic and rheumatoid articular cartilage. mRNA analysis showed besides an overall activation of synthetic activity in rheumatoid and osteoarthritic cartilage, a decreased expression of cartilage matrix proteins in the upper zone. The cease of the anabolic activity of rheumatoid and osteoarthritic chondrocytes and the increased catabolism of matrix components contributes to the anabolic-catabolic imbalance in rheumatoid and osteoarthritic cartilage and is suggestive to be a crucial event in the progress of the disease. It correlates well to the putative anti-anabolic effect of inflammatory cytokines such as II-1 and TNF-alpha and could indicate a potential role of these mediators in rheumatoid and osteoarthritic cartilage destruction.

Arthritis, Rheumatoid↗
PubMed1995

Potent pituitary-gonadal axis suppression and extremely low anaphylactoid activity of a new gonadotropin releasing hormone (GnRH) receptor antagonist "azaline B".

We report here the biological characterization of azaline B, a new gonadotropin releasing hormone (GnRH) receptor antagonist, with the following amino acid sequence: [Ac-D-Nal1, D-Cpa2, D-Pal3, Aph5(atz), D-Aph6(atz), Ilys8, D-Ala10]-GnRH. Azaline B was shown to suppress several reproductive processes in rats including ovulation, and had very low anaphylactoid activity compared with other GnRH antagonists. Azaline B inhibited histrelin (a GnRH agonist)-mediated follicle stimulating hormone (FSH) and luteinizing hormone (LH) release from cultured rat pituitary cells. Three antagonists ([Nal-Glu]-GnRH, [Nal-Lys]-GnRH ("antide"), and azaline B) inhibited 0.1 nM histrelin-mediated gonadotropin release to baseline levels with EC50 values of approximately 0.6 nM. Azaline B, when injected s.c. into rats on the afternoon of proestrus, was more potent at inhibiting ovulation than either [Nal-Glu]-GnRH or [Nal-Lys]-GnRH. The relative order of antiovulatory potencies of the three antagonists was azaline B > [Nal-Glu]-GnRH > [Nal-Lys]-GnRH. Similar azaline B potency was shown by its ability to suppress gonadotropin levels in castrated rats. The improved selectivity of azaline B was demonstrated when it was compared with other GnRH antagonists in the cutaneous anaphylactoid assay (local wheal response) in rats. Results with azaline B were not significantly different from results with vehicle in this assay. [Nal-Glu]-GnRH was more than twice as potent as [Nal-Lys]-GnRH in stimulating a wheal response. Furthermore, the maximal wheal response produced by azaline B was only 0.6 times that of [Nal-Lys]-GnRH, currently one of the most selective antagonists identified. Finally, both azaline B and [Nal-Lys]-GnRH were much less potent than [Nal-Glu]-GnRH in the guinea pig cardiopulmonary anaphylactoid assay after i.v. administration. These data show that azaline B is a potent and selective GnRH receptor antagonist with little or no anaphylactoid activity in animal models, and therefore has potential for use in the treatment of many reproductive endocrine disorders, as well as for use as a contraceptive.

Amino Acid Sequence↗
PubMed1995

Negative transcriptional regulation in anergic T cells.

Anergy is a mechanism of T-lymphocyte tolerance induced by antigen-receptor stimulation in the absence of costimulation, whereby T cells exhibit a defect in antigen-induced transcription of the interleukin 2 (IL-2) gene. Here we present evidence for a mechanism of negative IL-2 gene regulation in anergic T cells. High amounts of binding activity to the negative regulatory element A (NRE-A) of the IL-2 promotor were detected in nuclear extracts from human T cells shortly after induction of anergy. Rapid induction of this nuclear complex is blocked by cyclosporin A and is found to be independent of protein synthesis. Plasmid DNAs, containing either the human phorbol 12-myristate 13-acetate-responsive element (PRE) or both NRE-A and PRE, were used as template for in vitro transcription assays in the presence of T-cell nuclear extracts. Under these conditions nuclear extracts from both anergic and rested T-cell clones, after crosslinking of CD3 and CD28, induced transcription of plasmids containing only PRE. However, when plasmids containing NRE-A and PRE were used, transcription was only induced by nuclear extracts from rested but not anergic T cells. These findings suggest the functional relevance of transcriptional repression of the IL-2 gene in anergic T cells.

Antigens, CD↗
PubMed1995

Effect of atropine and bispyridinium oximes on respiratory and circulatory function in guinea-pigs poisoned by sarin.

During the past decade the oxime HI 6(1-[[[4-(aminocarbonyl)pyridinio]methoxy]methyl]-2- [(hydroxyimino)methyl] pyridinium dichloride) was shown to improve survival in nerve agent poisoning (in combination with atropine). Recent studies indicate, that HLö 7 (1-[[[4-(aminocarbonyl)pyridinio]methoxy]methyl]-2,4-bis [(hydroxyimino)methyl] pyridinium diiodide or dimethanesulfonate) is also an effective antidote in nerve agent poisoning but, with both oximes, data on restoration of respiration and circulation are scarce. The ability of HLö 7 or HI 6 with atropine to improve the respiratory and circulatory function in sarin-poisoned guinea-pigs was therefore investigated. Female Dunkin-Hartley guinea-pigs were anaesthetised with urethane (1.8 g/kg) and the arteria carotis, vena jugularis and trachea were cannulated. After baseline measurements the animals received 100 or 200 micrograms/kg sarin, and 2 min later the antidotes (all i.v.): 10 mg/kg atropine sulfate or a combination of atropine and HLö 7 or HI 6 (30 mumol/kg, each). Respiratory and circulatory parameters were recorded for the whole experimental period of 60 min or until the death of the animal. Brain and diaphragm acetylcholinesterase (AChE) activity was determined in each animal after the experiment. Poisoning by sarin resulted in a rapid respiratory arrest within 5 min. Atropine treatment was only partially effective in improving respiration after 100 micrograms/kg sarin but was ineffective after 200 micrograms/kg sarin. Therapy of sarin-poisoned animals with atropine plus oxime further improved respiration to various extents, restored circulation and increased survival time, HLö 7 being more effective than HI 6. Diaphragm and brain AChE were reactivated by HLö 7 and, to a minor extent, by HI 6. The results of this investigation suggest, that at equimolar doses (30 mumol/kg) the new bispyridinium dioxime HLö 7 has a higher therapeutic efficacy in sarin-poisoned guinea-pigs when compared to HI 6 (both in combination with atropine).

Acetylcholinesterase↗
PubMed1995

Growth and symptoms in Silver-Russell syndrome: review on the basis of 386 patients.

UNLABELLED: The spontaneous growth of 386 patients (163 girls and 223 boys) with Silver-Russell syndrome (SRS) was analysed in a mixed longitudinal and cross-sectional manner. One hundred and twenty patients were seen in the two centres between 1970 and 1993, additional definite cases were added from the literature. Mean (+/- SD) length of full-term babies with SRS at birth was 43.1 +/- 3.7 cm (n = 102) in both sexes. Mean weight at birth was 1940 +/- 353 g in boys and 1897 +/- 325 g in girls. During the first 3 years of life there was poor growth with a further loss in height. Between ages 4 and 10 years there was constant growth in parallel to the 3rd percentile with a mean height SDS of -4.3. The pubertal growth spurt was reduced in the whole group. Bone age development paralleled growth, retardation increased during the first years, remained constant during prepubertal time and caught up in early puberty. Mean adult height was 151.2 +/- 7.8 cm in males and 139.9 +/- 9.0 cm in females. Head circumference for age was in the lower normal range (mean SDS for 156 prepubertal boys -1.8; mean SDS for 97 prepubertal girls -2.2). CONCLUSION: Normative data on spontaneous growth of children with Silver-Russell syndrome are described, allowing a better counselling of patients as well as the judgement of the effects of growth promoting therapies.

Abnormalities, Multiple↗
PubMed1995

Reproducibility of a histogenetic classification of thymic epithelial tumours.

A histogenetic classification of thymic epithelial neoplasms proposed by Müller-Hermelink and co-workers has been shown by a number of recent studies to be of clinical and prognostic value. Reproducibility is an important criterion for the acceptance of any new classification for general diagnostic use. The reproducibility of this classification was tested on 51 cases of thymic epithelial neoplasia, by comparing results obtained by pathologists working from published criteria only with those results obtained by the pathologists who developed the classification. In 78% of cases there was complete concordance of results. Analysis of the 22% discordant cases showed that this discordance was due to a degree of subjectivity in determining cut-off points between categories adjacent to each other in the morphological spectrum of thymic epithelial neoplasia (medullary v. mixed, cortical v. well-differentiated thymic carcinoma). In terms of the important clinical distinction between benign (medullary and mixed) thymomas and those with more aggressive biological behaviour (cortical types and well-differentiated thymic carcinoma), the degree of reproducibility was 96%. The high degree of reproducibility of this histogenetic classification of thymic epithelial neoplasms should facilitate its acceptance and use in routine diagnostic pathology.

Adolescent↗
PubMed1995

Inflammatory, preneoplastic, and neoplastic changes of the gastric mucosa. Examinations by the AgNORT-technique.

The gastric surface epithelium of 101 antrum biopsies was examined by the AgNOR-technique. The material included normal mucosa, Helicobacter pylori gastritis, gastric ulcer, intestinal metaplasia type I and type III, dysplasia grades I-III and carcinoma. Starting from normal mucosa, a continuous increase in the number of AgNORs could be observed. At the same time, the size of the individual AgNOR-dots decreased. The entire AgNOR area per cell and the AgNOR quotient were ascertained. Groups of significant differences were found and could be clearly defined by cluster analysis. Intestinal metaplasia type I corresponded to inflammatory changes, whereas intestinal metaplasia type III was related to dysplastic lesions.

Biopsy↗
PubMed1994

[Immunoproliferative small intestinal disease (IPSID): an unusual form of gastrointestinal lymphoma].

Worsening of long-lasting diarrhea, abdominal discomfort and weight loss were main symptoms in a 27-year-old Moroccan woman who had lived in Germany for 18 years. Pseudomonas, salmonella and lamblia cysts were found in stools. Histological examination of the gastrointestinal tract showed immunoproliferative small intestinal disease (IPSID), characterized by atrophy of the villi and lymphoplasmocytic infiltrates. alpha 1-heavy chains were found immunohistologically in the biopsy specimen, but not in serum, urine or jejunal juice. HLA-typing gave evidence of A9. Antibiotic treatment was successful for almost one year. Clinical, histological and immunological diagnosis of IPSID in an African woman living for nearly 20 years in Europe shows that, besides environmental factors, genetic disposition is an essential factor in the development of IPSID.

Adult↗
PubMed1994

Neurofibromatosis presenting as a severe systemic vasculopathy.

In a boy with neurofibromatosis type 1 (NF-1), hypertension, septic infection of an aneurysm in the deltoid muscle, bowel infarction, multiple arterial aneurysms and venous thrombosis occurred within a period of 6 weeks. Histologically, vascular neurofibromatosis of the small vessels of the gut was found. This unusual occurrence of a multitude of clinical features within a few weeks was caused by vascular neurofibromatosis. Awareness of this condition in patients with NF-1 may help the paediatrician to avoid unnecessary diagnostic procedures and to initiate appropriate symptomatic therapy.

Arteries↗
PubMed1994

Treatment of tabun poisoned guinea-pigs with atropine, HLö 7 or HI 6: effect on respiratory and circulatory function.

The oxime HI 6 (in combination with atropine) is considered to be an effective antidote in soman intoxication but was shown to be less effective in tabun poisoning. In contrast to HI 6, first in vitro studies with HLö 7 demonstrated a reasonable reactivating potency at acetylcholinesterase (AChE) inhibited by soman and tabun. Therefore, the therapeutic efficacy of HLö 7, HI 6 and obidoxime (with and without atropine) was compared in tabun poisoned guinea-pigs. In addition, the therapeutic effect of atropine in guinea-pigs poisoned by various doses of tabun was investigated. Female Pirbright-white guinea-pigs were anaesthetized with urethane (1.8 g/kg) and the carotid artery, jugular vein and trachea were cannulated. After baseline measurements the animals received tabun, 60, 180 or 300 micrograms/kg, and 2 min later the antidotes (all i.v.): obidoxine, HLö 7, or HI 6 (30 or 100 mumol/kg, each) or atropine 10 mg/kg or a combination of atropine and one of the oximes. Respiratory and circulatory parameters were recorded for 60 min or until the death of the animal. Erythrocyte, brain and diaphragm AChE activity was determined in every animal after the experiment. Poisoning by tabun resulted in a rapid deterioration of respiratory function and respiratory arrest within 5 min. Atropine treatment was very effective in improving the respiratory function after tabun 60 micrograms/kg but was ineffective after tabun 300 micrograms/kg. However, circulatory parameters were restored almost completely in all atropine therapy groups. Therapy of tabun 300 microns/kg poisoned animals with atropine plus oxime (30 micromol/kg) improved respiration to a variable extent and restored circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Thyrotropin-producing hypophyseal adenoma in a case with congenital thyroid gland hypoplasia].

A 56 year old mentally disabled woman of short stature was admitted to our hospital because of severe chest pain and dyspnoea. An extended myocardial infarction in the anterior wall was clinically found and confirmed by autopsy. On admission cretinism with massive myxedema was diagnosed, which was confirmed by subsequent laboratory findings. Only at the base of the tongue thyroid tissue 3 mm in diameter was found. In the anterior lobe of the pituitary gland areas with nodular hyperplasia and microadenomas of TSH-producing cells were detected. Thyrotroph adenomas in long standing hypothyroidism are rare. There are only few reports on congenital hypothyroidism as primary underlying disease.

Adenoma↗
PubMed1994

Synergistic effects of trans-4-acetylaminostilbene and 2-acetylaminofluorene at the level of tumor initiation.

The synergism of two carcinogenic aromatic amines with different tissue specificities was studied at the level of initiation in Wistar rats. Gamma-glutamyl transpeptidase and glutathione S-transferase P were used as markers for preneoplastic foci in liver. 2-Acetylaminofluorene (AAF) is a complete rat liver carcinogen, whereas trans-4-acetylaminostilbene (AAS) produces ear duct tumors quite selectively, but also acts as a strong initiator in rat liver. When these carcinogens were administered sequentially as two doses of each or simultaneously as four doses of a mixture to neonate animals, which then were treated with phenobarbital in the drinking water for promotion, the initiating activity was additive. When these chemicals were given to young adult animals within 4 weeks in two series of four doses, followed by partial hepatectomy and phenobarbital in the drinking water, the number of preneoplastic foci was greater in groups which had received AAS in both series or in the second series after AAF than in those groups which had received only AAF or AAF in the second series. The average size of foci depended clearly on the sequence in which the two carcinogens were administered. The foci were larger when AAF was given after AAS. The results support the notion that AAS is a strong initiator in rat liver, and that AAF, which is a complete liver carcinogen, has promoting properties under certain circumstances in addition to its initiating properties. The two carcinogens seem to produce the initiating lesions independently but the extent of initiation is additive in this model situation. The simplified neonatal rat liver model appears to be particularly suitable for investigating initiating properties and is proposed for studies of synergistic effects of genotoxic chemicals on the initiation stage, independent of organotropism. It avoids a number of complicating factors related to treatment schedule, forced proliferation rate and toxicity in other models.

2-Acetylaminofluorene↗
PubMed1994

IgG monoclonal antibodies that inhibit osteoinductivity of human bone matrix-derived proteins (hBMP/NCP).

Monoclonal hBMP/NCP (human bone morphogenetic protein and associated noncollagenous proteins) antibodies of the IgG class were produced. In vitro, 12 of 19 hBMP/NCP antibodies showed functional inhibition of hBMP/NCP-induced chondroneogenesis in a neonatal muscle tissue assay. Inducing factors were characterized by their inhibiting antibodies with immunoblotting. Several peptide factors seem to be involved in the cascade of induced chondro- and osteogenesis.

Animals↗
PubMed1994

Monoclonal Epstein-Barr virus genomes but lack of EBV-related protein expression in different types of gastric carcinoma.

Thirty-nine resection specimens of gastric carcinomas have been investigated for the presence of EBV RNA sequences using a highly sensitive non-radioactive in situ hybridization technique. Transcribed EBER sequences were found in seven (18%), including four cases of undifferentiated carcinoma with prominent lymphoid infiltration and three gastric adenocarcinomas. In the positive tumours all, or nearly all, tumour nuclei were distinctly labelled. No positive signals could be detected in the non-dysplastic epithelial cells or the reactive inflammatory infiltrate. Clonality analysis using specific probes to the variable tandem repeat region of the EBV yielded single episomal bands in all four cases tested, two of which were undifferentiated carcinomas and two adenocarcinomas. By means of immunohistology, no expression of the EBV-related proteins LMP or EBNA-2 was present in tumour cells of positive cases in in situ or blotting attempts. Our results suggest that infection of gastric carcinomas by the EB virus occurs early in tumourigenesis but, in contrast to nasopharyngeal carcinomas, does not result in the expression of EBV-specific proteins.

Adenocarcinoma↗