PubMed Health⌕ Search

Biomedical subjects

P Dieter

Publications and source records attributed to P Dieter.

At least 19 recordsLinked to original sources
PubMed2005

[Teaching methods in anesthesia and intensive care medicine. The new legislation and its possibilities for the specialty].

BACKGROUND: As of October 1, 2003, a new government-initiated legislative basis for undergraduate medical education was initiated in Germany which resulted in substantial changes to the structure of the medical curriculum and in a heightened teaching load. METHODS: The Medical Faculty of the University of Dresden established an interdisciplinary reform curriculum in 1998. Since then a hybrid model of traditional lectures, seminars, practical and problem-based learning courses has been implemented for all courses in undergraduate medical training (Dresdener Integrated Problem-based Learning: DIPOL). RESULTS: Examplarly for all other DIPOL courses, the 2003 evaluation results of the "Emergency medicine-Injuries-Intensive care medicine" are presented and show that the course was very well received by students and tutors, and that 95% of the students passed the exams. CONCLUSIONS: The DIPOL anesthesiology course conforms with the new German federal law. A continuous further evaluation is an essential part of quality control and is necessary for the further development of a new curriculum.

Anesthesiology↗
PubMed2005

Characterization of macrophage subpopulations in colon cancer using tissue microarrays.

AIMS: To determine the pattern of macrophage infiltration in colon cancers and its correlation with clinicopathological characteristics. METHODS AND RESULTS: Colon cancers from 100 patients were arrayed into a tissue microarray (TMA). Four cores per tumour were taken: three from the invasion front (IF) and one from the tumour surface (TS). Macrophages were quantified by immunohistochemistry with antibodies to the PG-M1, KP-1, MRP8, MRP14 and MRP8/14 antigens. The number of macrophages was significantly higher in the TS cores than in the IF cores and both tumour sites showed a higher number of macrophages than the normal mucosa. The number of macrophages decreased in higher stage tumours. The different tumour-associated macrophage (TAM) subpopulations were positively correlated with each other. CONCLUSIONS: The increased number of macrophages in cancers compared with normal colon mucosa indicates that macrophages are attracted to the tumour site. However, decreasing macrophages in higher stage colon cancers suggest that this attraction decreases with tumour progression.

Aged↗
PubMed2000

Functional coupling of cyclooxygenase 1 and 2 to discrete prostanoid synthases in liver macrophages.

The profile of released prostanoids after addition of exogenous arachidonic acid to resident liver macrophages is different from the profile obtained in lipopolysaccharide-pretreated cells. In resident and lipopolysaccharide-pretreated cells, AA leads to a release of thromboxane B(2), prostaglandin F(2alpha), E(2), and D(2). A specifically enhanced formation of prostaglandin E(2) is obtained in lipopolysaccharide-pretreated cells. Resident liver macrophages express cyclooxygenase 1, and thromboxane A(2)-, prostaglandin F(2alpha)-, E(2)-, and D(2)-synthase. Treatment with lipopolysaccharide induces-in addition to cyclooxygenase 2-an enhanced expression of the prostaglandin E(2) synthase. In resident liver macrophages, the formation of prostanoids from exogenous arachidonic acid is completely inhibited by SC560 (a specific inhibitor of cyclooxygenase 1), but remains unchanged with SC236 (a specific inhibitor of cyclooxygenase 2). In lipopolysaccharide-pretreated liver macrophages, the formation of thromboxane B(2), prostaglandin F(2alpha) and D(2) is equally inhibited by SC560 and SC236 by about 50%. In contrast, the formation of prostaglandin E(2) is inhibited to a greater extent by SC560 (75%) compared to SC236 (26%). We conclude from these data, that in lipopolysaccharide-pretreated liver macrophages (i) cyclooxygenase 1 and 2 couple both to discrete prostanoid synthases, (ii) the functional coupling of cyclooxygenase 1 and 2 to the thromboxane A(2)-, prostaglandin F(2alpha)-, and D(2)-synthase is almost identical, and (iii) the enhanced prostaglandin E(2) synthesis is due to an enhanced expression of the prostaglandin E(2) synthase, which is coupled more efficiently to cyclooxygenase 1.

Animals↗
PubMed2000

Protein kinase C-alpha and -beta play antagonistic roles in the differentiation process of THP-1 cells.

The roles of protein kinase C (PKC) isoenzymes in the differentiation process of THP-1 cells are investigated. Inhibition of PKC by RO 31-8220 reduces the phagocytosis of latex particles and the release of superoxide, prostaglandin E(2) (PGE(2)), and tumour necrosis factor (TNF)-alpha. The proliferation of THP-1 cells is slightly enhanced by RO 31-8220. Stable transfection of THP-1 cells with asPKC-alpha, and incubation of THP-1 cells with antisense (as) PKC-alpha oligodeoxynucleotides reduces PKC-alpha levels and PKC activity. asPKC-alpha-transfected THP-1 cells show a decreased phagocytosis and a decreased release of superoxide, PGE(2) and TNF-alpha. The proliferation of asPKC-alpha-transfected THP-1 cells is enhanced. Stable transfection of THP-1 cells with asPKC-beta, and incubation of THP-1 cells with asPKC-beta oligodeoxynucleotides, reduces PKC-beta levels and PKC activity. asPKC-beta-transfected THP-1 cells show a decreased phagocytosis, a decreased TNF-alpha release, and a decreased proliferation. However, no difference is measured in the release of superoxide and PGE(2). These results suggest that: (1) PKC-alpha but not PKC-beta is involved in the release of superoxide and PGE(2); (2) TNF-alpha release and the phagocytosis of latex particles are mediated by PKC-alpha, PKC-beta, and other PKC isoenzymes; and (3) PKC-alpha and PKC-beta play antagonistic roles in the differentiation process of THP-1 cells. PKC-alpha promotes the differentiation process of THP-1 cells, PKC-beta retards the differentiation of THP-1 cells into macrophage-like cells.

Blotting, Western↗
PubMed1999

Prostaglandin E2 affects differently the release of inflammatory mediators from resident macrophages by LPS and muramyl tripeptides.

LPS and MTP-PE (liposome-encapsulated N-acetyl-muramyl-L-alanyl-D-isoglutaminyl-L-alanine-2-:[1',2'dipalmitoyl -sni-glycero-3-(hydroxy-phosphoryl-oxyl)] etylamide) induce in liver macrophages a synthesis and release of TNF-alpha, nitric oxide and prostanoids. Both agents induce an expression of mRNA's encoding TNF-alpha, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, and of corresponding proteins. LPS and MTP-PE induce a rapid activation of the extracellular regulated kinase (ERK) isoenzymes-1 and -2. Inhibition of map kinase isoenzymes leads to a decreased release of TNF-alpha, nitric oxide and prostaglandin (PG) E2 after both agents. The transcription factors NF-kappaB and AP-1 are strongly activated by LPS within 30 minutes. MTP-PE induces a weak activation of both transcription factors only after 5 hours. Inhibition of NF-kappaB inhibits the LPS- but not the MTP-PE-induced release of TNF-alpha, nitric oxide and PGE2. PGE2 release after LPS is higher than after MTP-PE. Exogenously added PGE2 inhibits the activation of map kinase and TNF-alpha release by LPS, but not by MTP-PE. Release of nitric oxide after LPS and MTP-PE is enhanced after prior addition of PGE2. PGD2 is without any effect. MTP-PE, but not LPS, induces a cytotoxicity of Kupffer cells against P815 tumor target cells. The MTP-PE-induced cytotoxicity is reduced by TNF-alpha neutralizing antibodies, indicating the involvement of TNF-alpha. Thus our results suggest that the different potencies of LPS and MTP-PE as immunomodulators probably result from different actions on Kupffer cells, resulting in differences in the amounts and kinetics of released TNF-alpha and PGE2, and that PGE2 plays an important regulatory role in the action of LPS, but not in the actions of MTP-PE.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1998

Nucleophosmin-anaplastic lymphoma kinase of large-cell anaplastic lymphoma is a constitutively active tyrosine kinase that utilizes phospholipase C-gamma to mediate its mitogenicity.

Large-cell anaplastic lymphoma is a subtype of non-Hodgkin's lymphoma characterized by the expression of CD30. More than half of these lymphomas have a chromosomal translocation, t(2;5), that leads to the expression of a hybrid protein comprised of the nucleolar phosphoprotein nucleophosmin (NPM) and the anaplastic lymphoma kinase (ALK). Here we show that transfection of the constitutively active tyrosine kinase NPM-ALK into Ba/F3 and Rat-1 cells leads to a transformed phenotype. Oncogenic tyrosine kinases transform cells by activating the mitogenic signal transduction pathways, e.g., by binding and activating SH2-containing signaling molecules. We found that NPM-ALK binds most specifically to the SH2 domains of phospholipase C-gamma (PLC-gamma) in vitro. Furthermore, we showed complex formation of NPM-ALK and PLC-gamma in vivo by coimmunoprecipitation experiments in large-cell anaplastic lymphoma cells. This complex formation leads to the tyrosine phosphorylation and activation of PLC-gamma, which can be corroborated by enhanced production of inositol phosphates (IPs) in NPM-ALK-expressing cells. By phosphopeptide competition experiments, we were able to identify the tyrosine residue on NPM-ALK responsible for interaction with PLC-gamma as Y664. Using site-directed mutagenesis, we constructed a comprehensive panel of tyrosine-to-phenylalanine NPM-ALK mutants, including NPM-ALK(Y664F). NPM-ALK(Y664F), when transfected into Ba/F3 cells, no longer forms complexes with PLC-gamma or leads to PLC-gamma phosphorylation and activation, as confirmed by low IP levels in these cells. Most interestingly, Ba/F3 and Rat-1 cells expressing NPM-ALK(Y664F) also show a biological phenotype in that they are not stably transformed. Overexpression of PLC-gamma can partially rescue the proliferative response of Ba/F3 cells to the NPM-ALK(Y664F) mutant. Thus, PLC-gamma is an important downstream target of NPM-ALK that contributes to its mitogenic activity and is likely to be important in the molecular pathogenesis of large-cell anaplastic lymphomas.

Animals↗
PubMed1997

Infiltration of lung carcinomas with macrophages of the 27E10-positive phenotype.

In order to gain insight into the role of macrophages in human lung carcinomas, we investigated material from 35 lung carcinomas and 5 healthy lungs with 4 different antibodies (CD68, MRP8, MRP14, 27E10) recognizing different macrophage subtypes. Infiltration with CD68-positive macrophages was highest and comparable in healthy lungs and lung carcinomas. Compared to healthy lungs, the infiltration of MRP8- and MRP14-positive macrophages was reduced in lung carcinomas while the number of 27E10-positive cells was enhanced. No difference in the infiltration of macrophages was observed between the different histological subtypes of carcinomas such as squamous carcinoma, small lung carcinoma, adenocarcinoma and bronchio-alveolar carcinoma. Furthermore, we present a highly suitable technique for the isolation and enrichment of macrophages from human lung carcinomas resulting in a 5-10 fold enrichment and a yield of e.g. 2-3 x 10(6) 27E10-positive macrophages/g tumor biopsy. Together with the recent findings that 27E10-positive macrophages are prevalent in early acute inflammation and release cytotoxic mediators and to inhibit tumor cell proliferation our findings suggest that 27E10-positive macrophages may play a role in antitumor cytotoxicity in human lung carcinomas.

Antibodies, Neoplasm↗
PubMed1996

Differences in the state of differentiation of THP-1 cells induced by phorbol ester and 1,25-dihydroxyvitamin D3.

Human THP-1 leukemia cells differentiate along the monocytic lineage following exposure to phorbol-12-myristate-13-acetate (PMA) or 1,25-dihydroxyvitamin D3 (VD3). In the monocytic cell line THP-1, PMA treatment resulted in a more differentiated phenotype than VD3, according to adherence, loss of proliferation, phagocytosis of latex beads, and expression of CD11b and CD14. Both differentiating substances induced similar effects in the release of superoxide anions (O2-). VD3-differentiated cells did not release prostaglandin E2 (PGE2), in contrast to PMA-differentiated cells, and in PMA-differentiated cells phospholipase A2 (PLA2) activity and expression was increase. Lipopolysaccharide (LPS)-stimulated tumor necrosis factor-alpha (TNF-alpha) release was higher in PMA-treated cells. PMA- but not VD3-differentiation resulted in a translocation of protein kinase C (PKC) isoenzymes to membrane fractions. Both differentiating agents up-regulated the expression of PKC isoenzymes. Whereas VD3 elevated mainly the expression of PKC-beta, PMA caused a strong increase in PKC-delta and a weak increase in PKC-alpha, PKC-epsilon, and PKC-zeta expression. These results indicate that phorbol ester and the active metabolite of vitamin D induce different signal pathways, which might result in different achievement of differentiation.

Blotting, Western↗
PubMed1995

Role of cytosolic phospholipase A2 in arachidonic acid release of rat-liver macrophages: regulation by Ca2+ and phosphorylation.

In this study we have verified the existence of a cytosolic phospholipase A2 (cPLA2) in rat-liver macrophages. Stimulation of these cells with phorbol 12-myristate 13-acetate (PMA), zymosan and lipopolysaccharide (LPS), but not with the Ca(2+)-ionophore A23187, leads to phosphorylation of cPLA2 and activation of mitogen-activated protein (MAP) kinase, supporting the hypothesis that MAP kinase is involved in cPLA2 phosphorylation. We show furthermore, that the tyrosine kinase inhibitor genistein prevents the LPS- but not the PMA- or zymosan-induced phosphorylation of cPLA2 and activation of MAP kinase, indicating that tyrosine kinases participate in LPS- but not in PMA- and zymosan-induced cPLA2 phosphorylation and MAP kinase activation. Phosphorylation of cPLA2 does not strongly correlate with stimulation of the arachidonic acid (AA) cascade: (1) A23187, a potent stimulator of AA release, fails to induce cPLA2 phosphorylation; (2) withdrawal of extracellular Ca2+, which inhibits PMA-stimulated AA release (Dieter, Schulze-Specking and Decker (1988) Eur. J. Biochem. 177, 61-67), has no effect on PMA-induced phosphorylation of cPLA2; (3) LPS induces cPLA2 phosphorylation within minutes, whereas increased AA release upon treatment with LPS is detectable for the first time after 4 h; and (4) genistein, which prevents LPS-induced cPLA2 phosphorylation, does not inhibit AA release in response to LPS. From these data we suggest that a rise in intracellular Ca2+, but not phosphorylation of cPLA2, is essential for activation of the AA cascade in rat-liver macrophages.

Animals↗
PubMed1995

Comparative studies of cytotoxicity and the release of TNF-alpha, nitric oxide, and eicosanoids of liver macrophages treated with lipopolysaccharide and liposome-encapsulated MTP-PE.

LPS and liposome-encapsulated MTP-PE induce liver macrophages cytotoxicity against tumor target cells and a release of TNF-alpha, nitric oxide, and eicosanoids but not a generation of superoxide anions. Neither agent elicits a formation of inositol phosphates, a change in intracellular free calcium, or a translation of protein kinase C-beta. Inhibition or down-regulation of protein kinase C does not inhibit the release of TNF-alpha and nitric oxide but inhibits the formation of prostanoids. In contrast to LPS, liposome -encapsulated MTP-PE induces an elevation of diacylglycerol mass and an enhanced expression of protein kinase C-delta. LPS, but not liposome-encapsulated MTP-PE, elicits an enhanced expression of cytosolic phospholipase A2 and a predominant formation of PGE2. Both agents elicit different responses when given to cells pretreated with one of the immunomodulators, with dexamethasone, or with PGE2. In contrast, to liposome-encapsulated MTP-PE, LPS induces only cytotoxicity when added to liver macrophages simultaneously or a maximum of 2 h before the addition of tumor target cells. The observed differences might reflect partly differences in the potencies of LPS and some liposome-encapsulated MTP-PE as immunomodulators.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1995

Differential regulation of phospholipase D and phospholipase C by protein kinase C-beta and -delta in liver macrophages.

We have studied activation of phospholipase (PL) C and PLD in liver macrophages labelled with [3H]arachidonic acid. Zymosan, phorbol 12-myristate 13-acetate (PMA), A23187 and fluoride but not arachidonic acid or lipopolysaccharide (LPS) induce an activation of PLD ([3H]phosphatidylethanol (PEt) accumulation). An activation of PLC ([3H]diacylglycerol (DAG) accumulation) is measured with zymosan, PMA and fluoride but not with A23187, LPS or arachidonic acid whereas inositol phosphates are formed with zymosan, only. Removal of extracellular calcium reduces the formation of [3H]PEt and [3H]DAG while pretreatment of the cells with dexamethasone reduces [3H]PEt formation, only. PMA- and zymosan-induced activation of PLD and PMA-induced activation of PLC both seem to be mediated by protein kinase (PK) C-beta whereas zymosan-induced activation of PLC is negatively controlled by PKC-delta. We could furthermore present evidence that the release of [3H]arachidonic acid in these cells occurs independent of an activation of PLD.

Animals↗
PubMed1994

Arachidonic acid and eicosanoid release.

The major techniques for the study and determination of eicosanoid metabolism in eukaryotic cells will be described. These techniques include the determination of free arachidonic acid and its metabolites in biological fluids and cell media by immunochemical techniques (RIA, ELISA) and by HPLC. The different methods will be explained and critically compared.

Animals↗