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Biomedical subjects

U Kohler

Publications and source records attributed to U Kohler.

At least 19 recordsLinked to original sources
PubMed2001

Mutational analysis of the PRL receptor gene in human breast tumors with differential PRL receptor protein expression.

PRL is a major growth and differentiating hormone in the human breast, with activation of the PRL-PRL receptor complex increasingly recognized as an important mechanism in the induction and progression of mammary tumors. Although constitutive activation of various hormone and growth factor receptors is newly recognized as a common cause of tumor development, the PRL receptor gene has not been analyzed for similar aberrations in breast and other tumors. Therefore, using bacterial artificial chromosomes containing the PRL receptor gene and intron-spanning PCR, we determined the exon-surrounding intron sequences providing primers for the first analysis of the entire coding region of the human PRL receptor gene. We examined the presence of PRL receptor in 41 breast tumors by immunohistochemistry and attempted a correlation of its expression to pathological grading of the disease. Then tumor cells were isolated by laser capture microdissection to examine DNA from 30 patients for PRL receptor mutations. The PRL receptor immunoreactive score did not correlate to the tumor size, histopathological grading, age, or family history of patients. PRL receptor immunoreactivity was predominantly found in steroid hormone receptor-positive tumors, but without overall correlation of immunoreactive score. In both PRL receptor-positive and PRL receptor- negative breast cancer cells, direct sequencing of the coding sequence of the PRL receptor gene did not detect any somatic or hereditary gene aberrations. In conclusion, PRL receptor mutations do not appear to be common in human breast cancer, suggesting that constitutive activation of the PRL receptor can be excluded as a major cause of mammary tumor genesis. The molecular structure of the PRL receptor seems to remain intact in tumor tissue, and systemic and local production of PRL may participate in tumor cell growth and proliferation through functional receptors.

Adult↗
PubMed1997

[Ulcus cruris venosum].

The conservative treatment of venous crural ulcer is frustrating, and a recurrency rate of 25% is seen. Even after surgical treatment of the underlying venous disease, long-lasting septic complications and persistent wound infection occur. The combination of ESDP, paratibial fasciotomy and vacuum sealing therapy is a modern concept of varicose vein surgery. For the first time we are able to present a concept of surgery to cure venous crural ulcer definitely within an acceptably short period.

Combined Modality Therapy↗
PubMed1988

Dynamic changes in plasma membrane properties of Semliki Forest virus infected cells related to cell fusion.

The mechanism of the processes leading to membrane fusion is as yet unknown. In this report we demonstrate that changes in membrane potential and potassium fluxes correlate with Semliki Forest virus induced cell-cell fusion at mildly acidic pH. The changes observed occur only at pH's below 6.2 corresponding to values required to trigger the fusion process. A possible role of these alterations of the plasma membrane related to membrane fusion phenomena is discussed.

Adenosine Triphosphate↗
PubMed1988

Exposure of Semliki Forest virus-infected baby hamster kidney cells to low pH leads to a proton influx and a rapid depletion of intracellular ATP which in turn prevents cell-cell fusion. Brief report.

The conditions needed to trigger Semliki Forest virus (SFV) induced cell-cell fusion from within (FFWI) of baby hamster kidney (BHK) cells differs from some other cells (e.g., Aedes albopictus cells). In contrast to such cells it is mandatory for BHK cells to be brought back to a neutral pH after a short exposure to mildly acidic pH for fusion to occur. This phenomenon can be explained by a sudden drop of the intracellular pH observed after clamping the extracellular pH below 6.2--the pH required to trigger fusion--and by the thereby implied increased expenditure of ATP. Since the fusion from within of SFV-infected cells is energy dependent [Kempf et al. (1987) Arch Virol 95: 111-122] the fusion process is blocked due to the ATP depletion.

Adenosine Triphosphate↗
PubMed1987

Can viral envelope proteins act as or induce proton channels?

The mechanism of the process leading to cell-cell fusion induced by enveloped viruses at a mildly acidic pH is as yet unknown. In this report we demonstrate that the fusion events induced by three viruses of different families, namely Semliki Forest (togavirus), vesicular stomatitis (rhabdovirus) and influenza (orthomyxovirus), share common features. In all three systems a sudden drop of the intracellular pH--below the critical extracellular pH required to trigger "fusion from within" (FFWI)--is observed. This influx of protons is specific and not due to a general leakiness of the plasma membrane, and therefore might be caused by the opening of a proton channel.

Aedes↗
PubMed1987

A novel method for the detection of early events in cell-cell fusion of Semliki Forest virus infected cells growing in monolayer cultures.

Semliki Forest virus infected Aedes albopictus cells were used to investigate virus induced cell-cell fusion. It was shown by a novel method that cell-cell fusion was completed within approximately 5 minutes after triggering the fusion event by low pH. This method consists of fixing fusing cells with glutaraldehyde and microinjecting the highly fluorescent and rapidly diffusing dye Lucifer yellow. In contrast, polykaryon formation, the usually used criterion to measure cell-cell fusion occurred only within 30 minutes. Furthermore, it was shown that potassium cyanide, a potent inhibitor of polykaryon formation in the described system, inhibits an early step of membrane-membrane fusion of neighbouring cells.

Aedes↗
PubMed1987

Semliki Forest virus-induced polykaryocyte formation is an ATP-dependent event.

Infection of Aedes albopictus cells with Semliki Forest virus (SFV) leads to polykaryocyte formation below pH 6.2. This syncytium formation is accompanied by a decrease of the cellular ATP level. Addition of inhibitors of oxidative phosphorylation leads to a rapid, total depletion of ATP in infected cells at pH 6 and results in an inhibition of polykaryocyte formation. However, when cells were exposed for only a few minutes to pH 6 in the presence of the inhibitors and then kept at pH 7.2, the ATP level partially recovered to values sufficient for syncytium formation. Similar results were obtained after ATP depletion induced by 2-deoxyglucose. Thus, it can be concluded that SFV-induced syncytium formation is an ATP-dependent event.

Adenosine Triphosphate↗
PubMed1986

Fusion of Semliki Forest virus infected Aedes albopictus cells at low pH is a fusion from within.

Herein, it is shown for the first time that the mechanism of fusion followed in Aedes albopictus cells infected with Semliki Forest virus induced by low pH exposure is a "fusion from within". Several parameters were studied disclosing that the development of the fusion capacity of the cells is directly related to the synthesis of viral specific products. These findings were further substantiated by utilizing various chemicals to inhibit viral specific events during infection, protein synthesis and maturation. Removal of exogenous virions produced at 16 hours post infection by proteinase K digestion clearly revealed that the viral proteins located at the cell surface and not the exogenous virions were responsible for the fusogenic activity. The presence of these viral proteins at the cell surface was disclosed by immunofluorescence employing anti-SFV antibodies elicited in rabbits. Additional evidence for the participation of the viral proteins at the cell surface in the fusion reaction was obtained by Bromelaine digestion which inhibited the fusion and tunicamycin treatment which only partially inhibited the fusion but revealed the inevitable presence of the E1 protein.

Aedes↗
PubMed1985

Conformational changes at pH 6 on the cell surface of Semliki Forest virus-infected Aedes albopictus cells.

The mechanism of Semliki Forest virus-induced fusion from within at low pH was studied in Aedes albopictus cells. The fusion was found to occur in at least two steps, namely, a fast initial step which is pH dependent and temperature independent, and a second slower process which is pH independent and temperature dependent. The initiation step induced by low pH exposure constitutes an irreversible conformational change of a protein probably of viral origin located at the cell surface.

Aedes↗
PubMed1984

Morphologic investigation of coronary arteries subjected to hypertension by experimental supravalvular aortic stenosis in dogs.

A sustained and gradual development of hypertension in coronary arteries of 16 foxhounds was induced by afterload stress with supravalvular aortic stenosis. Dogs were perfusion fixed after 4 months and 1 year of stenosis for morphologic analysis of coronary arteries with scanning electron microscopy, transmission electron microscopy, and light microscopy. Mean prestenotic pressures and SD standard deviations in millimeters of mercury for perfusion-fixed foxhounds after 4 months were systolic 141 +/- 14, mean arterial 101 +/- 8, and diastolic 81 +/- 7, and after 1 year systolic 182 +/- 31, mean arterial 128 +/- 22, and diastolic 101 +/- 16. Scanning electron microscopy results of coronary arteries subjected to 4 months of hypertension show little change from normal coronary arteries. Only isolated cases of desquamating endothelial cells were seen directly proximal to ostia of coronary arteries. Transmission electron microscopy showed no ultrastructural changes in this banding group. In four of six foxhounds subjected to 1 year of hypertension, scanning electron microscopy observations of coronary arteries revealed one to five areas of endothelial denudation, typically oriented parallel to the longitudinal axis of the artery, a few cell diameters wide and 100 to 300 microns in length. These lesions were often seen to form narrow channels between two or more branching points, either in a continuous or in series fashion. Platelets, lymphocytes, granulocytes, and monocytes adhered to the subendothelial surface. Occasional denudations were oriented transversely to the longitudinal axis. Denudations were restricted to arteries greater than 1.2 mm in diameter. In the vicinity of denudation lesions, lymphocytes and monocytes adhered to endothelium showing alterations in cell size and shape. Transmission electron and light microscopy of this banding group showed breaks and duplication of the internal elastic lamina and smooth muscle proliferation in the intima. Focal areas of intimal inflammatory reactions, sometimes superimposed upon intimal proliferative changes, were noted in those areas exhibiting luminal cell adherence to endothelium. The results indicate that the morphologic equivalent of hypertension varies depending on the manner in which it is experimentally produced. The findings of intimal proliferation and late endothelial denudation give support to the response-to-injury hypothesis for the pathogenesis of atherosclerosis and suggest a mechanism for the role of hypertension as a risk factor.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1979

Increase of interferon antiviral activity by exogenous cyclic adenosine-3':5'-monophosphate (cAMP).

Some effects of cAMP on replication of Semliki Forest Virus in chick embryo fibroblast cell cultures are described. Depending on concentration, the incorporation of [3H]-uridine into viral RNA or the formation of plaque-forming units is inhibited; the highest concentration tested was 8 mM. Cyclic AMP has an effect of its own and increases the Interferon action in the lower concentration ranges of Interferon (up to 1 unit/ml). The effect of cyclic AMP is fast, needs no induction and is also visible in late phases of viral replication. However, these experiments do not establish a causal relation between cAMP and Interferon.

Cyclic AMP↗
PubMed1979

Altered or increased transfer-RNA methylation in the course of Interferon action on cells in culture?

The induction of the antiviral state by Interferon might reflect the decrease of the rate of biosynthesis, the degradation or the alteration of one or several tRNAs. This could result in rate-limiting concentrations for codons common in viral RNA but rare in host mRNA. Altered methylation of tRNA could be the basis of such a phenomenon. However, we could not find an altered extent of methylation of total tRNA or an altered pattern of methylation, if mixed tRNAs were chromatographed on MAK- or BD-cellulose columns, despite a large range of conditions of pretreatment of chick embryo fibroblast cultures with interferon.

Animals↗
PubMed1978

Kinetics of interferon action.

A kinetic analysis of the action of interferon with different preparations in chick embryo fibroblast cell culture gives additional evidence for interaction of interferon with the cell surface, compatible with the idea that interferon is not taken up by the cells. With certain assumptions the binding constant is in the range of 10(13) [l/Mol].

Cell Membrane↗
PubMed1976

EOG: light test and dark test.

The EOG test is divided into two parts: a light and a dark test. The adaptation period is extended to 30 min. During this adaptation period the luminance in the cabin decreases (or increases) slowly to the starting value of the light or dark step. In a model, we studied the influence of this ramplike luminance course on the results. Standard values for the test were calculated with 30 test persons. Our test results show a lower relative standard deviation (V = 10%) compared with earlier published results.

Adaptation, Ocular↗