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G Köhler

Publications and source records attributed to G Köhler.

At least 145 records · Page 8Linked to original sources
PubMed1990

Non-tolerance and differential susceptibility to diabetes in transgenic mice expressing major histocompatibility class II genes on pancreatic beta cells.

In insulin-dependent diabetes mellitus aberrant expression of major histocompatibility complex (MHC) class II antigens might induce autoimmune destruction of insulin-producing pancreatic beta cells. Here we demonstrate that already the expression of single MHC class II chains (E alpha k and E beta b) is sufficient to cause diabetes without affecting beta cell morphology and cell numbers. Our transgenes interfere at least in two points of insulin production leading to a severely diabetic phenotype. In one case E beta b expression led to a 10-30-fold decrease of mouse insulin mRNA. In another case E alpha k expression reduced insulin secretion to background levels. In addition, we also found a patchy distribution of both insulin and E alpha k expression, indicating heterogeneity of the beta cell population, without the concomitant development of diabetes. Although the transgenic E alpha k E beta b MHC class II molecules were expressed on the surface of pancreatic beta cells, the transgenic mice did not prove to be tolerant for I-E antigen. Autoimmune reactions remained absent showing that aberrant MHC class II expression on pancreatic beta cells alone is not sufficient for the development of autoimmune diabetes in mice.

Animals↗
PubMed1990

[Mucinous cystadenoma of the pancreas--exact endoscopic assessment with pancreoscopy].

Mucinous cystadenomas of the pancreas are rare tumors of the exocrine pancreas with a well-documented risk for malignant degeneration. We present 2 patients with this cystic pancreatic neoplasia who were admitted with signs of obstructive pancreatitis. The exact diagnosis was found preoperatively by a new endoscopic technique: mother-baby duodenoscopy. The small-caliber endoscopy allows the precise description of intraductal tumors. Histological resp. cytological specimens obtained under direct optical control, allow for an exact pathoanatomical classification. This modern endoscopic system is an important addition for diagnosing intraluminal tumors of the hepato-biliary system.

Biopsy↗
PubMed1989

Elimination of CD8+ thymocytes in transgenic mice expressing an anti-Lyt2.2 immunoglobulin heavy chain gene.

Individual T cell populations are characterized by specific surface proteins, namely by the T cell receptor complex (TCR) and by two accessory molecules, CD8 (Lyt2) and CD4 (L3T4). CD8 and CD4 are required for T cell interactions with class I or class II major histocompatibility complex molecules. In the thymus, immature CD8(-4)-TCR- cells differentiate, possibly via a short stage of CD8+4- thymocytes, into CD8+4+ TCR+ T cells and mature further into the main T cell populations, the CD8+4- TCR+ cytotoxic T lymphocytes and the CD4+8- TCR+ T helper cells. In order to analyse the differentiation steps involving CD8, we generated transgenic mice expressing mu heavy chain genes from an anti-Lyt2.2 hybridoma. Transgenic lines expressing either the complete (mu sm) or only the secreted mu protein (mu s) suffer from a severe depletion of their CD8+4+ thymocytes affecting also the mature CD8+4- and CD4+8- populations. The depletion is correlated to the expression of transgenic mu-chain proteins within thymocytes. This intrathymocyte expression of the mu chain prevents CD8-4- thymocytes from further differentiation, most probably via intracellular interactions between mu heavy chain and CD8 proteins. These results show that CD8 plays an important role during thymocyte maturation.

Animals↗
PubMed1989

Immune status of a mu, kappa transgenic mouse line. Deficient response to bacterially related antigens.

We have examined the immune repertoire and immune response of a mouse that carries transgenes for a mu heavy chain and kappa light chain. The expression of these genes is under the regulation of their own controlling elements. The transgenes are expressed early in ontogeny and are easily detectable from day 13 of gestation onwards. The pre-B cells seem to function normally as they generate IgM-secreting colonies at normal frequencies. Colonies show predominantly the transgenic specificity. Expression of the transgenes is not limited to B cells since around 10%-20% of peripheral T cells and 50% of thymocytes express the mu transgene as an intracellular protein. Ectopic expression of kappa was not seen. The spleen size of the transgenic mouse is decreased by around 20%; this reduction is largely caused by a reduction of the B cell pool. Almost all B cells express the transgenes, only 30% co-express endogenous heavy chain genes and all co-express endogenous light chain genes. Serum Ig levels for IgM and IgA were normal, 20% of the IgM consist of the transgenic product. Serum IgG levels were decreased. T cell functions (helper and cytotoxic) were normal. Immune responses to conventional antigens were impaired, especially in the early phases of the immune response, but after boosting they were virtually normal, except for IgG3 which remained low. Primary antibody responses to T cell-independent antigens of the class II type (bacterially related antigens) were absent, although precursor frequencies for these antigens were within the expected range. The significance of this finding, as it relates to allelic exclusion of Ig genes, is discussed.

Animals↗
PubMed1989

Analysis of T-cell subpopulations in human IL-2R alpha transgenic mice: expansion of Thy1.2- thymocytes and depletion of double-positive T-cell precursors.

Transgenic mice carrying the human IL-2R alpha/p55 gene under the control of the SV40 enhancer/promoter were used to study the relevance of IL-2R in T-cell development. Serological analysis of the mouse lines obtained indicated transient, regulated expression of the human p55 gene, mainly confined to the early thymus, but which was also detected in lower amounts in the spleen. These mice showed degenerated thymuses, with an increased number of Thy1.2- double-negative precursor cells; they also had specific depletion of double-positive thymocytes. Transgene expression led to an increased number of intermediate-affinity IL-2 receptors (possibly ascribed to deregulated expression of IL-2R beta/p75) in transgenic thymocytes older than 12 weeks. These results suggest the occurrence of strong linkage between the IL-2/IL-2R system elements and thymic differentiation/maturation; they lend support to the idea of functionality of IL-2R expressed transiently in early stages of T-cell development.

Animals↗
PubMed1989

Carbohydrate metabolism during treatment of endometriosis with the progestin dienogest.

Eight otherwise healthy women aged 17 to 38 years with endometriosis were treated with 2 mg of the progestin dienogest daily for 24 weeks. Blood glucose and plasma insulin were measured prior to and during an intravenous glucose tolerance test before and after 1, 3 and 6 months use of the oral progestin. There were no significant changes in fasting glucose and in glucose levels after the glucose load during the therapy though the fasting glucose levels tended to be higher under dienogest. The basal insulin values remained unchanged but the insulin response was slightly insignificantly increased after 10 and 20 minutes following glucose application depending on the duration of therapy. The data suggest that 2 mg dienogest administered daily has no or only a very slight influence on carbohydrate metabolism.

Adolescent↗
PubMed1989

Lipid metabolism during treatment of endometriosis with the progestin dienogest.

The effects of a new progestational compound, dienogest (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4,9-dien-3-one) on lipid metabolism have been studied in 84 otherwise healthy women with laparoscopically proven endometriosis. The women, aged 17 to 45, years were treated with 2 mg dienogest in tablet form daily for 24 weeks. The progestin was highly effective on endometriotic lesions and symptoms, showing an objective endoscopic and a subjective symptomatic improvement in 80% and 83% respectively. Triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol and the LDL-cholesterol/HDL-cholesterol ratio were determined before and after 1, 3 and 6 months use of the progestin. There was a maximum decrease of -5.8% in HDL-cholesterol and of -6.5% in triglycerides after 6 months of therapy vis-à-vis the pretreatment values. The maximum increase in LDL-cholesterol of +5.0% was recorded by the end of the first month of dienogest ingestion. The LDL-cholesterol/HDL-cholesterol ratio rose from 1.6 to 1.8 during the course of therapy. There were no significant changes. The data suggest that 2 mg dienogest has little influence on lipid metabolism and provides also in this respect a suitable approach to the hormonal therapy of endometriosis.

Adolescent↗
PubMed1989

[Endometriosis and laparoscopy].

Endometriosis in an important disease especially for girls and young women. It often causes chronic complaints and infertility, requiring an early endoscopic diagnosis for their prophylaxis and therapy. The characteristics of endometriosis, the indications for laparoscopy, its technique, and the endoscopic picture are described in detail. The knowledge of the special endoscopic features is essential, otherwise there will be a high percentage of false negative diagnostic results. Reducing the failure rate in endometriosis diagnosis is the aid of this survey.

Diagnosis, Differential↗
PubMed1989

[Behavior of parameters of liver metabolism in intermediate-term use of the gestagen dienogest in the treatment of endometriosis].

The effects of the progestational compound dienogest (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4,9-dien-3-one) on liver metabolism have been studied in 101 otherwise healthy women with endoscopically proven endometriosis. The women aged 17 to 45 years were treated with 2 mg dienogest in tablet form daily for 24 weeks. Aspartate amino transferase (ASAT), alanine amino transferase (ALAT), gamma glutamate transferase (GGT), alkaline phosphatase (AP), lactate dehydrogenase (LDH), and total bilirubin (BILI) were determined in serum before and after 1, 3 and 6 months use of the progestin. During the therapy period no deviations from the normal ranges were found. There was a slight significant decrease of ASAT and ALAT and a slight significant increase of LDH and BILI (p less than 0.05) remaining within the normal laboratory values. Since no undesirable metabolic side-effects have so far been observed with dienogest, it may be considered an effective new alternative treatment for endometriosis.

Adolescent↗
PubMed1988

[Steroid-refractory amiodarone-induced pulmonary fibrosis. Clinical features and morphology after an amiodarone-free interval of 3 months].

Amiodarone-induced bilateral diffuse pulmonary fibrosis developed in a 47-year-old woman with idiopathic hypertrophic subvalvular aortic stenosis who had been treated with amiodarone (Cordarex), 300 mg daily for about 18 months. Although the drug was discontinued and cortisone treatment begun, the pulmonary fibrosis did not regress. When gentamicin (Refobacin) and cefotaxime (Claforan) were administered for suspected fibrosis-induced right-sided bronchopneumonia, gentamicin-induced acute tubular renal damage occurred, requiring dialysis. The patient died soon after of myocardial electro-mechanical dissociation. At necropsy there was, in addition to the idiopathic hypertrophic subvalvular cardiomyopathy, extensive bilateral pulmonary fibrosis, lamellar bodies in foam-cell intraalveolar macrophages, in hepatocytes and in the epithelium of the proximal and distal tubules. Although amiodarone had been discontinued three months previously, high concentrations of the drug were still present, especially in both lungs, fat tissue and the liver.

Adipose Tissue↗
PubMed1988

Expression, distribution and specificity of Fc receptors for IgM on murine B cells.

Subpopulations of normal adult murine splenic B cells and a panel of murine B cell tumors were examined for their ability to bind murine IgM specifically. By using two-color flow cytometric analyses, we have demonstrated that 90 to 95% of surface (s)IgD+ B cells express surface membrane receptors for IgM (Fc mu R). The binding of pentameric murine IgM to splenocyte Fc mu R was IgM-specific since it was totally inhibited by other polymeric IgM proteins, but not by Ig of other H chain classes or by mAb specific for the murine IgG or IgE FcR. Binding of IgM to splenic cells was saturable. Fc mu R were co-expressed with the Fc gamma R as well as the Fc epsilon R on the majority of splenic B cells. Minor populations of splenic mononuclear cells expressed only an Fc mu R, Fc gamma R or Fc epsilon R. In a survey of B tumor cell lines representing different stages of B cell development, we observed that the Fc mu R was expressed on pre-B cell lines and that Fc mu R detection was maximal on immature B cell lines that expressed sIgM and low amounts of sIgD and Ia. Fc mu R were not detected on cell lines that had switched from sIgM to the expression of another sIg, or on plasmacytomas and hybridomas. The studies with normal splenocytes establish that the majority of sIgD+ B lymphocytes in adult BALB/c mice express surface membrane receptors that specifically bind IgM. The studies with B lineage tumor cells suggest that the expression of Fc mu R on B cells is developmentally regulated and that the pattern of expression exhibited by Fc mu R during B cell ontogeny differs from the patterns that have been previously found for IgG and IgE FcR. These observations raise the possibility that Fc mu R might have a functional significance in some aspect of B cell maturation and activation. By using a family of IgM H chain constant region domain deletional mutants, we have further demonstrated that, like the T cell Fc mu R, the B cell Fc mu R also requires a C mu 3 domain for binding to occur, raising the possibility that the T and B cell Fc mu R in mice may be structurally related molecules.

Animals↗