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Biomedical subjects

M Grebe

Publications and source records attributed to M Grebe.

16 recordsLinked to original sources
PubMed2007

Planar polarity of root hair positioning in Arabidopsis.

The co-ordinated polarity of cells within the plane of a single tissue layer (planar polarity) is intensively studied in animal epithelia but has only recently been systematically analysed in plants. The polar positioning of hairs in the root epidermis of Arabidopsis thaliana provides an easily accessible system for the functional dissection of a plant-specific planar polarity. Recently, mutants originally isolated in genetic screens for defects in root hair morphogenesis and changes in the sensitivity to or the production of the plant hormones auxin and ethylene have identified players that contribute to polar root hair placement. Here, we summarize and discuss recent progress in research on polar root hair positioning from studies in Arabidopsis.

Animals↗
PubMed2005

Changes in extracranial arteries in obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is linked with increased cardiovascular morbidity and mortality, possibly through an enhancement of atherosclerotic vascular changes. Up to now, however, only a few studies have tried to evaluate the occurrence of atherosclerosis in patients with OSA. In the present study, ultrasonography of the large extracranial vessels was performed in a group of consecutively admitted OSA patients (n = 35) and a control group of non-OSA patients (n = 35). Common carotid artery-intima media thickness (CCA-IMT) was measured at the far wall of both proximal carotid arteries. Furthermore, the presence of plaques and stenoses of the extracranial vessels was determined. All measurements were carried out blinded to the status of the patients. In the OSA group, CCA-IMT was significantly increased when compared with the non-OSA patients and was related to the degree of nocturnal hypoxia. Additionally, the formation of plaques was more pronounced and extracranial vessel stenosis was more common in the OSA patients. In conclusion, these findings are in favour of an independent influence of obstructive sleep apnoea on atherosclerotic changes of the arterial wall, and represent further strong arguments for obstructive sleep apnoea being a risk factor on its own for the emergence of cardiovascular disease.

Age Distribution↗
PubMed2004

[Persistent angina pectoris in spite of successful myocardial revascularisation].

A 73-year-old obese woman underwent coronary artery-bypass operation in 11/1995 because of a coronary two vessel disease. The left coronary artery was bypassed by the left mammarial internal artery. In 2 and 3/2002, balloon-dilatation of stenoses of the right coronary artery and the circumflex was performed. Angina pectoris relapsed and in 9/2002 the patient was admitted to our hospital with tentative diagnosis of restenosis. Physical investigation showed a blood pressure of the right arm of 160/80 and of the left arm of 120/ 80 mmHg. Coronarography showed the three vessel disease known since 2/2002 with a restenosis of the right coronary artery which was immediately treated by balloon-dilatation and stent-implantation. Colour duplex-sonography of the carotid and subclavian arteries revealed extraordinary plaques and a reduced flow of the left vertebral artery. The left subclavian artery could only be seen distal to the discharge of the vertebral artery and showed a poststenotic flow. The patient had angina pectoris when carrying out personal hygiene already 2 days after balloon-dilatation and stent-implantation. ECG showed new aspects. Coronarography showed no relapse of stenosis, but 70% stenosis of the left subclavian artery with a marked coronary-steal-syndrome. In 10/ 2002, the patient underwent balloon-dilatation and stent-implantation of the subclavian stenosis and became free of complaints. Coronary-steal-syndrome can be the reason for persistent angina pectoris in spite of successful coronary artery-bypass operation with a mammarial internal bypass. It is absolutely necessary to take blood pressure from both arms to recognise a possible stenosis of the subclavian artery which can be the key to all.

Aged↗
PubMed2001

Functional characterization of the KNOLLE-interacting t-SNARE AtSNAP33 and its role in plant cytokinesis.

Cytokinesis requires membrane fusion during cleavage-furrow ingression in animals and cell plate formation in plants. In Arabidopsis, the Sec1 homologue KEULE (KEU) and the cytokinesis-specific syntaxin KNOLLE (KN) cooperate to promote vesicle fusion in the cell division plane. Here, we characterize AtSNAP33, an Arabidopsis homologue of the t-SNARE SNAP25, that was identified as a KN interactor in a yeast two-hybrid screen. AtSNAP33 is a ubiquitously expressed membrane-associated protein that accumulated at the plasma membrane and during cell division colocalized with KN at the forming cell plate. A T-DNA insertion in the AtSNAP33 gene caused loss of AtSNAP33 function, resulting in a lethal dwarf phenotype. atsnap33 plantlets gradually developed large necrotic lesions on cotyledons and rosette leaves, resembling pathogen-induced cellular responses, and eventually died before flowering. In addition, mutant seedlings displayed cytokinetic defects, and atsnap33 in combination with the cytokinesis mutant keu was embryo lethal. Analysis of the Arabidopsis genome revealed two further SNAP25-like proteins that also interacted with KN in the yeast two-hybrid assay. Our results suggest that AtSNAP33, the first SNAP25 homologue characterized in plants, is involved in diverse membrane fusion processes, including cell plate formation, and that AtSNAP33 function in cytokinesis may be replaced partially by other SNAP25 homologues.

Amino Acid Sequence↗
PubMed2001

Tamoxifen sensitivity-testing of glioblastomas: comparison of in vitro and in vivo results.

BACKGROUND: Only less than half of the patients with malignant gliomas respond to a continuous high dose Tamoxifen (TAM) and/or Carboplatin (CP)-treatment. Therefore, a method for predicting the efficacy of TAM-treatment would be desirable. METHODS: Paralleling a clinical study, the predictive value of in vitro-sensitivity testing of TAM and TAM's metabolite 4-OH-TAM in primary cultures of tumour explants from 15 of a total of 50 patients was examined. Additionally, the influence of TAM, 4-OH-TAM, and CP on the proliferation of established glioblastoma cell lines and of those explanted from athymic nude mice and re-established in cell culture was investigated. Human glioblastomas xenotransplanted subcutaneously into athymic nude mice and subsequently treated with TAM and/or CP were examined in a parallel in vivo-study. FINDINGS: TAM-chemosensitivity-testing of glioblastomas failed to predict the clinical response to TAM-treatment in our patients and did not correlate with the in vivo-TAM-response of tumours xenotransplanted into nude mice. TAM's and 4-OH-TAM's ability to inhibit growth of various glioblastoma cell lines in vitro in very similar concentrations was shown to be a consistent phenomenon which seems to be independent of the in vivo response in either patients or mice as previous hosts. However, CP's antiproliferative effect on glioblastomas in vivo was paralleled by respective in vitro results. Whereas TAM showed to mediate its in vitro antiproliferative effect by inducing apoptosis in most cell lines examined, CP-treatment lead to necrosis of cells. INTERPRETATION: Combining the results obtained from our human and mouse studies, it has to be postulated that host factors other than the sensitivity to TAM of the individual cell, determine the efficacy of TAM-treatment in vivo.

Adult↗
PubMed2001

Cell axiality and polarity in plants--adding pieces to the puzzle.

Plant cell polarity is important for cellular function and multicellular development. Classical physiological and cell biological analyses identified cues that orient cell polarity and suggested molecules that translate a cue into intracellular asymmetry. A range of proteins that either mark or are involved in the establishment of a (polar) axis are now available, as are many relevant mutants. These tools are likely to facilitate a dissection of the molecular mechanisms behind cell and organ polarity in the near future.

Cell Differentiation↗
PubMed2000

Characterization of subclones of the epithelial cell line from Chironomus tentans resistant to the insecticide RH 5992, a non-steroidal moulting hormone agonist.

Selection of hormone resistant subclones in the continuous presence of the insecticide and ecdysteroid mimick RH 5992 (tefubenozide) resulted preferentially in clones with defects in ecdysteroid receptor function. RH 5992 is already degraded to polar products in wild-type cells; no increase in metabolism of tefubenozide is observed in resistant clones. According to Western blots, ecdysteroid receptor (EcR) and its heterodimerization partner ultraspiracle (USP) are present in all resistant clones. The concentrations are comparable to wild-type cells, but in three clones the extent of phosphorylation of USP is diminished. With regard to hormone binding several types of hormone resistance are distinguished: (1) The same two high-affinity hormone recognition sites are present as in wild-type cells (K(D1)=0.31+/-0.28 nM, K(D2)=6.5+/-2.4 nM) but the number of binding sites is reduced. (2) The binding site with the lower affinity (K(D2)) is missing. (3) The binding site with the higher affinity (K(D1)) is missing. (4) No specific binding is observed. Ponasterone A binding can be rescued by addition of EcR but not by USP. (5) Ligand specificity is altered. RH 5992 can not compete [(3)H]-ponasterone A as efficient as in wild-type cells.

Animals↗
PubMed2000

A conserved domain of the arabidopsis GNOM protein mediates subunit interaction and cyclophilin 5 binding.

The Arabidopsis GNOM protein, a guanine nucleotide exchange factor (GEF) that acts on ADP ribosylation factor (ARF)-type G proteins, is required for coordination of cell polarity along the apical-basal embryo axis. Interallelic complementation of gnom mutants suggested that dimerization is involved in GNOM function. Here, direct interaction between GNOM molecules is demonstrated in vitro and by using a yeast two-hybrid system. Interaction was confined to an N-terminal domain conserved within a subgroup of large ARF GEFs. The same domain mediated in vitro binding to cyclophilin 5 (Cyp5), which was identified as a GNOM interactor in two-hybrid screening. Cyp5 displayed peptidylprolyl cis/trans-isomerase and protein refolding activities that were sensitive to cyclosporin A. Cyp5 protein accumulated in several plant organs and, like GNOM, was partitioned between cytosolic and membrane fractions. Cyp5 protein was also expressed in the developing embryo. Our results suggest that Cyp5 may regulate the ARF GEF function of the GNOM protein during embryogenesis.

ADP-Ribosylation Factors↗
PubMed1999

Coordinated polar localization of auxin efflux carrier PIN1 by GNOM ARF GEF.

The plant hormone auxin is transported in a polar manner along the shoot-root axis, which requires efflux carriers such as PIN1. Asymmetric localization of PIN1 develops from a random distribution in Arabidopsis early embryogenesis. Coordinated polar localization of PIN1 is defective in gnom embryos. GNOM is a membrane-associated guanine-nucleotide exchange factor on ADP-ribosylation factor G protein (ARF GEF). Thus, GNOM-dependent vesicle trafficking may establish cell polarity, resulting in polar auxin transport.

ADP-Ribosylation Factors↗
PubMed1998

Ecdysteroid receptor and ultraspiracle from Chironomus tentans (Insecta) are phosphoproteins and are regulated differently by molting hormone.

Three different isotypes of the ecdysteroid receptor (cEcR) (66, 68 and 70 kDa) and several molecular variants of the dimerization partner "ultraspiracle" (cUSP) (58-77 kDa) can be separated electrophoretically in homogenates of the epithelial cell line from Chironomus tentans. After phosphatase treatment the bands with the lowest electrophoretic mobility disappear in both cases. Phosphorylation occurs exclusively at ser/thr in EcR and USP. Binding studies with 3H-ponasterone A using 0.4 M NaCl extracts revealed two classes of high-affinity binding (KD1 = 0.47 and KD2 = 7.2 nM) competable either with 20-OH-ecdysone or muristerone A. At least KD2 and Bmax2 are unchanged after dephosphorylation. In hormonally naive cells a considerable part of EcR and USP is already present in nuclei. The phosphorylation pattern of both transcription factors is the same in cytosol and nuclear fractions. Incubation with 20-OH-ecdysone (1 microM, up to 4 days) does not alter the extent and mode of phosphorylation of EcR, although EcR concentration increases. In contrast USP concentration remains constant but phosphorylation is enhanced.

Animal Structures↗
PubMed1997

Establishment of cell polarity during early plant development.

Cellular asymmetries have been proposed to play a role in plant embryogenesis. Genetic studies of Arabidopsis and other experimental approaches in several plant species have addressed the origins of cellular asymmetry in specific cases. Although zygote polarity, which precedes the formation of the apical-basal axis of the embryo, is normally aligned with that of the surrounding maternal tissue, isolated single somatic cells that give rise to embryos in culture appear to become polar in the absence of maternal factors. Gene expression patterns reveal the developmental consequences of cellular asymmetries occurring at later stages of embryogenesis. Genetic evidence suggests that these cellular asymmetries are established in response to as yet unidentified signals from adjacent cells.

Cell Communication↗
PubMed1995

Patterns of cytokine gene expression in peripheral T-cell lymphoma of angioimmunoblastic lymphadenopathy type.

Peripheral T-cell lymphoma of angioimmunoblastic lymph-adenopathy type (AILD-TCL) is histologically characterized by a mixed infiltrate of atypical T cells, B cells including B immunoblasts, and plasma cells, as well as eosinophilic granulocytes accompanied by proliferated high endothelial venules, while, clinically, fever and weight loss are often observed. These morphologic and clinical pecularities are widely believed to reflect abnormal patterns of cytokine expression. To evaluate this hypothesis, 11 lymph nodes with AILD-TCL were studied for the presence of tumor necrosis factor-alpha (TNF), lymphotoxin (LT), interleukin-6 (IL-6), and IL-1 beta transcripts by in situ hybridization (ISH) using [35S]-labeled cytokine-specific RNA probes in seven cases subsequent to immunohistology for cell type characteristic antigens. Expression of all four cytokines was strongly enhanced in AILD-TCL when compared with the control groups of lymphoblastic lymphomas and peripheral T-cell lymphomas, other than AILD-TCL. TNF and LT transcripts were present in atypical T cells and in a variable proportion of B immunoblasts in all AILD-TCL cases, whereas IL-6 and IL-1 beta specific transcripts were mainly found in nonlymphoid cells. To verify a possible cytokine expression by Epstein-Barr virus (EBV)-infected cells, which are frequently present in AILD-TCL, the detection of EBV-encoded nuclear RNAs (EBER) was combined with ISH for cytokine transcripts. It became evident that expression of LT and TNF by EBV-infected cells was largely restricted to B immunoblasts, which were only infrequently present in most AILD-TCL cases, whereas the expression of IL-6 was very rare, and IL-1 beta was not found in EBV-infected cells. These data suggest that expression of TNF and LT genes may contribute to the characteristic histologic and clinical features of AILD-TCL and that cytokine expression by EBV-infected cells does not, in most cases, contribute significantly to the overall cytokine expression. Because it has been shown that LT is an autocrine growth factor for EBV-infected B cells, expression of this cytokine could contribute to the proliferation of EBV-infected B cells in AILD-TCL and, in the setting of immunosuppression, may ultimately play a role in the development of B-immunoblastic lymphomas.

Cytokines↗
PubMed1993

Lymphotoxin, tumour necrosis factor and interleukin-6 gene transcripts are present in Hodgkin and Reed-Sternberg cells of most Hodgkin's disease cases.

Tissue specimens from 26 cases of Hodgkin's disease (HD) and six HD-derived cell lines were analysed for tumour necrosis factor (TNF), lymphotoxin (LT), and interleukin (IL)-6 RNA transcripts by in situ hybridization, in some cases subsequent to immunohistology for CD30 antigen. LT and TNF transcripts were found in tumour cells of all cases; IL-6 gene transcripts were detectable in 19/23 cases. Presence of RNA specific for these cytokines was not correlated with any of the following parameters: sex, symptoms and histotype, as well as immunophenotype and association of the tumour cells with Epstein-Barr virus. Rather, the presence of LT, TNF and IL-6 transcripts appeared to characterize Hodgkin and Reed-Sternberg cells in general, supporting concepts which suggest that HD represents a malignancy of cytokine secreting activated cells, and that many of the features distinguishing HD from other malignant lymphomas may ultimately be due to expression of cytokines. LT and TNF RNA transcripts were also found in five HD-derived cell lines, whereas supernatants of these cell lines contained high levels of LT, but low or undetectable levels of TNF activity. This suggests that, although not detectable at the level of RNA transcripts, differences between HD cases may exist on the level of cytokine gene transcript processing, translation and polypeptide secretion.

Adolescent↗
PubMed1989

Value of thyroid hormone determination.

Free thyroid hormone assays have broadened the repertoire in thyroid diagnosis. At elevated binding protein levels they provide more reliable information on the metabolic state than do total hormone determinations; yet under estrogen contraception free T4 may yield test specifically falsely too high data. As a rule, there is accordance between free hormone concentrations and the indices, being equivalent in establishing the free thyroid hormone fraction. In this light the Thyroid Section of the German Endocrinologic Society recommended in 1986 to consider determinations of free or total hormone concentrations with calculation of the indices as being of equal value. In borderline situations the TRH test, the hypersensitivity TSH assay as well as checkups establishing the course of development of the disorder are substantiated.

Adolescent↗