Biomedical subjects

P Eder

Publications and source records attributed to P Eder.

8 recordsLinked to original sources

PubMed2007

TRPC3: a multifunctional, pore-forming signalling molecule.

TRPC3 represents one of the first identified mammalian relatives of the Drosophila trp gene product. Despite intensive biochemical and biophysical characterization as well as numerous attempts to uncover its physiological role in native cell systems, this channel protein still represents one of the most enigmatic members of the transient receptor potential (TRP) superfamily. TRPC3 is significantly expressed in brain and heart and likely to play a role in both non-excitable as well as excitable cells, being potentially involved in a wide spectrum of Ca2+ signalling mechanisms. Its ability to associate with a variety of partner proteins apparently enables TRPC3 to form different cation channels in native cells. TRPC3 cation channels display unique gating and regulatory properties that allow for recognition and integration of multiple input stimuli including lipid mediators and cellular Ca2+ gradients as well as redox signals. The physiological/pathophysiological functions of this highly versatile cation channel protein are as yet barely delineated. Here we summarize current knowledge on properties and possible signalling functions of TRPC3 and discuss the potential biological relevance of this signalling molecule.

Animals↗

PubMed2006

Phospholipase C-dependent control of cardiac calcium homeostasis involves a TRPC3-NCX1 signaling complex.

OBJECTIVE: Members of the classical transient receptor potential protein (TRPC) family are considered as key components of phospholipase C (PLC)-dependent Ca2+ signaling. Previous results obtained in the HEK 293 expression system suggested a physical and functional coupling of TRPC3 to the cardiac-type Na+/Ca2+ exchanger, NCX1 (sodium calcium exchanger 1). This study was designed to test for expression of TRPC3 (transient receptor potential channel 3) and for the existence of a native TRPC3/NCX1 signaling complex in rat cardiac myocytes. METHODS: Protein expression and cellular distribution were determined by Western blot and immunocytochemistry. Protein-protein interactions were investigated by reciprocal co-immunoprecipitation and glutathione S-transferase (GST)-pulldown experiments. Recruitment of protein complexes into the plasma membrane was assayed by surface biotinylation. The functional role of TRPC3 was investigated by fluorimetric recording of angiotensin II-induced calcium signals employing a dominant negative knockdown strategy. RESULTS: TRPC3 immunoreactivity was observed in surface plasma membrane regions and in an intracellular membrane system. Co-immunolabeling of TRPC3 and NCX1 indicated significant co-localization of the two proteins. Both co-immunoprecipitation and GST-pulldown experiments demonstrated association of TRPC3 with NCX1. PLC stimulation was found to trigger NCX-mediated Ca2+ entry, which was dependent on TRPC3-mediated Na+ loading of myocytes. This NCX-mediated Ca2+ signaling was significantly suppressed by expression of a dominant negative fragment of TRPC3. PLC stimulation was associated with increased membrane presentation of both TRPC3 and NCX1. CONCLUSION: These results suggest a PLC-dependent recruitment of a TRPC3-NCX1 complex into the plasma membrane as a pivotal mechanism for the control of cardiac Ca2+ homeostasis.

Animals↗

PubMed2005

Interobserver variation for ultrasound determination of thyroid nodule volumes.

Thyroid ultrasound is used in the routine clinical assessment and the follow-up of thyroid disorders. The follow- up of patients with thyroid nodules is mostly based on thyroid nodule volume determinations performed by different observers. However, for the judgment of treatment effects there is uncertainty about the interobserver variation of thyroid nodule volume measurements by ultrasound because there are no prospective blinded studies available comparing the interobserver variation in thyroid nodule volume measurement. The aim of our study was therefore to determine the variation of thyroid nodule volume determinations for different observers. We conducted a prospective blinded trial. Our study population consisted of 42 probands (8 men, 34 women) with an uniform distribution of thyroid nodule sizes (25 uninodular and 17 multinodular thyroid glands). We compared the results of 3 ultrasonographers with certified experience in thyroid ultrasound. The interobserver variation for the determination of thyroid nodule volume (n = 38) was 48.96% for the ellipsoid method and 48.64% for the planimetric method. The interobserver variation for determining thyroid volume (n = 40) was 23.69% for the ellipsoid method and 17.82% for the planimetric method. A regression analysis revealed that the probability for the identification of the same nodule in nodular thyroids by all sonographers is 90%, if the nodule is at least 15mm in greatest diameter. Future investigations should not describe changes in nodule volume less than 50% as therapy effects because only volume changes of at least 49% or more can be interpreted as nodule shrinkage or growth. Reporting of nodule volume modification 50% or more and lack of information for ultrasound procedures introduce a bias in studies evaluating the effects of nodule treatments. The clinical interpretation of a shrinking/growing thyroid nodule based on volume determinations by ultrasound is not well established because it is difficult to reproduce a two-dimensional image plane for follow-up studies.

Adult↗

PubMed1999

Amyloidosis--an unusual case of recurrent intestinal bleeding and sigmoid perforation: case report with review of the literature.

We describe a patient with recurrent intestinal bleeding and sigmoid perforation due to amyloidosis. Hartmann's procedure was carried out with resection of the diseased sigmoid colon and by performing a terminal colostomy. The postoperative course was uneventful, but the patient died 3 months later of lobar pneumonia and multiple organ system failure.

Abdominal Pain↗

PubMed1997

Cyclic AMP negatively controls c-myc transcription and G1 cell cycle progression in p210 BCR-ABL transformed cells: inhibitory activity exerted through cyclin D1 and cdk4.

Raised intracellular cyclic AMP (cAMP) has been demonstrated to exert an antiproliferative effect in myeloid cells. How the antiproliferative activity of cAMP is exerted in p210 BCR-ABL transformed myeloid cells was the subject of this investigation. It was hypothesized that cyclin dependent kinase 4, cdk4, might be a critical target enzyme to affect the related events of c-myc transcription and progression through G1 phase of the cell cycle within cells transformed by p210 BCR-ABL, and further, that cdk4 might be downregulated by cAMP to inhibit proliferation. In order to investigate the regulatory role of cdk4, synchronized cells were studied. In p210 BCR-ABL transformed cells transiting early G1 phase, treatment with a cAMP analogue led to inhibition of cyclin D1 synthesis, and marked reduction of cdk4 kinase activity. Within cells in which cdk4 was inhibited by cAMP, there was augmented interaction of E2F1 with the retinoblastoma protein, pRb in a nuclear matrix-associated cell fraction. As a result of E2F1 sequestration, raised intracellular cAMP was found to inhibit c-myc transcription in p210 BCR-ABL transformed myeloid cells synchronously transiting the early G1 phase of the cell cycle. A target of this transcriptional suppression exerted by cAMP was the E2F site of the c-myc P2 promoter. On the other hand, cyclin D1 content was not reduced by cAMP in these cells when it was applied at a later cell cycle stage at the interface between G1 and S. Corresponding to lack of cyclin D1 inhibition in these later G1-to-S phase cells, cdk4 activity was only modestly suppressed, and c-myc mRNA expression was also inhibited to a lesser degree. These studies show that Rb interaction with E2F1 is regulated by cdk4 and cyclin D1 within p210 BCR-ABL transformed leukemia cells in early G1 phase of the cell cycle. In this context, both cyclin D1 and cdk4 are subject to the level of intracellular cAMP. This interaction between Rb and E2F1, which is subject to the level of cAMP, is critical to transcriptional control of c-myc. Further, pRb regulation of E2F activity affects cellular potential for G1-S phase transition in p210 BCR-ABL transformed myeloid cells, in part, via its effect on c-myc transcription.

Animals↗

PubMed1996

Isolation of primitive human bone marrow hematopoietic progenitor cells using Hoechst 33342 and Rhodamine 123.

In addition to possessing multilineage differentiation and self-renewal capabilities, pluripotent hematopoietic stem cells are believed to be mitotically quiescent and metabolically inactive. Fractions of human bone marrow (BM) CD34+ cells can be further enriched for primitive hematopoietic progenitor cells (HPC) by using a number of cell-surface markers. All of these fractions, however, contain cells that are still heterogeneous as far as their metabolic and mitotic activities are concerned. We therefore used Hoechst 33342 (Hst) to identify quiescent cells and Rhodamine 123 (Rh123) to identify metabolically inactive cells. CD34+HstdimRh123dim (CD34+d/d) and CD34+HstbrightRh123bright (CD34+b/b) cells were isolated by flow cytometry to examine the hematopoietic functions of mitotically and metabolically homogeneous progenitors. Cell-cycle status, progenitor cell content, maintenance of in vitro hematopoiesis, and long-term hematopoietic culture-initiating cell (LTHC-IC) content of CD34+d/d and CD34+b/b cells were compared with CD34+HLA-DR- cells, a well-defined phenotype of primitive HPC. Whereas 99.2 +/- 0.5% of freshly isolated CD34+d/d cells were in G0/G1 phase of the cell cycle, only 74.4 +/- 11.5% of CD34+b/b and 75.6 +/- 1.1% of CD34+HLA-DR- cells were in G0/G1. The number of multipotential progenitors (colony-forming units-granulocyte/erythroid/ macrophage/megakaryocyte [CFU-GEMM]) detected in CD34+d/d cells was twice that observed in CD34+HLA-DR- cells and eight times that in CD34+b/b cells. In stromal cell-free long-term cultures maintained for 10 weeks, production of assayable progenitors in cultures initiated with CD34+d/d cells exceeded that detected in CD34+HLA-DR- cultures by more than three-fold. Only in CD34+d/d cultures were high proliferative potential colony-forming cell (HPP-CFC)-derived colonies detected over a period of 6 weeks. Limiting dilution analysis revealed that the frequency of LTHC-IC was highest among CD34+d/d cells (7.2 +/- 3.3%), followed by a frequency of 4.5 +/- 4.8% for CD34+HLA-DR- cells and 2.2 +/- 3.5% for CD34+b/b cells. The primitive nature of HPC identified by CD34, Hst, and Rh123 was confirmed by the ability of as few as 200 murine marrow cells isolated by this technique to radioprotect and fully reconstitute lethally irradiated recipients. These results indicate that Hst and Rh123 staining can be used in combination with CD34 immunofluorescence to isolate a quiescent subpopulation of human primitive hematopoietic progenitor cells. Cells isolated by this technique appear to have functional properties associated with stem cells, suggesting that they may be ideal candidates for studies requiring primitive HPC, such as ex vivo expansion and somatic gene therapy.

Adult↗

PubMed1989

Bone marrow autotransplantation for solid tumors--prospects.

Autologous bone marrow transplantation (AuBMT) is in clinical trial for patients with metastatic solid tumors, particularly breast cancer. This review deals with the potential of this approach. AuBMT is curative for the leukemias and lymphomas. Curative cancer chemotherapy has, almost without exception, required combinations of agents wherein dose was well maintained. However, curative chemotherapy strategies for the hematologic neoplasms have not proven successful for the common solid tumors. An important exception is that standard adjuvant chemotherapy can "cure" some micrometastatic tumors. Preclinical studies indicate the effectiveness of alkylating agents in terms of maintained dose effect through multiple logs of tumor cell kill; difficulty in developing drug resistance; general lack of cross resistance; and synergy for alkylating agents used in combination. There is an increasingly effective experimental basis for the construct of intensification regimens employing combinations of alkylating agents. Differing nonmyelosuppressive toxicity for alkylating agents provides a basis for maintaining dose when employed in combination in the autologous marrow situation. The aforementioned studies and cytokinetic analyses of combined intensive alkylating agent therapy for breast cancer support the potential of this approach. Clinical trials indicate a high response rate in refractory breast cancer. Trials involving induction chemotherapy followed by combined alkylating agent intensification have produced substantial complete remission rates. The duration of response has, in most studies, been short. This approach is associated with major toxicity, including mortality, and is expensive. Experimental and preliminary clinical evidence as marshalled in this review indicate that this is a promising area for therapeutic research.

Antineoplastic Agents↗

PubMedDate not supplied

Increased density of glutamate receptor subunit 1 due to Cerebrolysin treatment: an immunohistochemical study on aged rats.

Glutamate receptor subunit 1 (GluR1) is one of the four possible subunits of the AMPA-type glutamate receptor. The integrity of this receptor is crucial for learning processes. However, reductions of GluR1 are noticeable in the hippocampal formation of patients suffering from Alzheimer's disease. Such degradations presumably result in an impaired synaptic communication and might be causally linked to the neurodegenerative process in this cognitive disorder. The peptidergic drug Cerebrolysin counteracts cognitive deficits of patients affected by Alzheimer's disease. These findings are supported by experiments revealing neuroprotective and neurotrophic capacities of the drug. In order to examine the effect of the drug on the density of GluR1 in hippocampal formation 24-month-old rats were treated with either Cerebrolysin or its peptide fraction E021, or saline as a control. Spatial navigation of the animals was tested in the Morris water maze. Rat brain slices were stained immunohistochemically with a GluR1-specific antibody. GluR1 immunoreactivity was quantified using light microscopy and a computerised image analysis system. Cerebrolysin and E021 increased GluR1 density in most measured regions of the hippocampal formation in a highly significant way. These results correlate with the behavioural outcome, revealing an improvement in learning and memory of these rats after treatment with Cerebrolysin and E021.

Aging↗