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Biomedical subjects

M Zieger

Publications and source records attributed to M Zieger.

At least 19 recordsLinked to original sources
PubMed2004

Burn injuries in children with attention-deficit/hyperactivity disorder.

PURPOSE: Children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for traumatic injury than non-ADHD-children. Burn injuries in ADHD-children have not been studied. This study was conducted to determine differences in burn injuries between these groups. METHODS: The charts of all children ages 5-18, admitted over a 7-year period to a single regional pediatric burn center, were reviewed. ADHD-children were compared to non-ADHD-children regarding age and gender, type and extent of burn, and burn injury outcome. FINDINGS: There were 278 children included, 35 (13%) having ADHD. ADHD-children were more likely male but did not differ in age compared to non-ADHD-children. ADHD-children were more likely to experience a thermal rather than flame burn (83% versus 58% thermal, P < 0.01) and had more extensive burn injury (10% versus 5% median TBSA, P = 0.03). The ADHD group had a longer length of stay (11 versus 7 days, P = 0.05) and was less likely to be discharged to home (86% versus 93%, P = 0.17). CONCLUSIONS: ADHD-children do differ from non-ADHD-children in their pattern and extent of burn injury. The impulsivity and vigilance deficits that characterize ADHD may place these children at higher risk for specific types of burn injuries.

Adolescent↗
PubMed2002

The serine proteinase thrombin promotes migration of human renal carcinoma cells by a PKA-dependent mechanism.

In this study, we demonstrated that thrombin activates protein kinase C (PKC), mitogen activated protein kinases (MAP kinases), transcription factor nuclear factor-kappa B (NF-kappa B), and cAMP-dependent protein kinase (PKA) in the human renal carcinoma cell line A-498. In addition, it enhanced the migratory capacity, but had no effect on the proliferation of A-498 cells. The effect of thrombin on migration could be blocked by the PKA inhibitor H-89 but was not influenced by inhibition of PKC, MAP kinases or NF-kappa B. We concluded, that thrombin acts as a regulator on human A-498 renal carcinoma cell migration including PKA.

Cell Division↗
PubMed2001

Evidence for a novel thrombopoietin signalling event: activation of protein kinase A in human megakaryoblastic CMK cells.

Thrombopoietin (TPO) plays a crucial role in megakaryocyte development. TPO signalling, which is mediated by its receptor Mpl, includes Janus kinase, (JAK) signal transducer and activator of transcription (STAT) and Shc/Ras/mitogen-activated protein kinase (MAPK) pathways. The precise nature of these signalling routes has not been clarified in detail up until now. We investigated the effect of TPO on activation of cAMP-dependent protein kinase (PKA) and its involvement in MAPK signalling in human megakaryoblastic leukaemia CMK cells. For estimation of PKA activity, phosphorylation of a PKA-specific peptide substrate was assayed in CMK cell lysates. Since activation of PKA is associated with translocation of its catalytic subunit alpha (C-PKA) into the cell nucleus, Western blot analysis of nuclear fractions with an anti-C-PKA antibody was additionally performed. The activation of TPO-induced MAPK activation and the effect of the PKA inhibitor H-89 was measured using immunoblotting with a monoclonal anti-pERK antibody. TPO enhanced cAMP and induced activation of PKA in CMK cells. In addition, H-89 partly blocked TPO-induced MAPK activation in CMK cells. Our results indicate a novel TPO-triggered signalling event, activation of the cAMP/PKA pathway in human megakaryoblastic CMK cells. This signal transduction route seems to be involved in TPO-induced MAPK signaling.

Cell Nucleus↗
PubMed2001

A novel PAR-1-type thrombin receptor signaling pathway: cyclic AMP-independent activation of PKA in SNB-19 glioblastoma cells.

Cellular effects of thrombin are mediated by members of a new subfamily of G protein-coupled receptors designated proteinase-activated receptors (PARs) with the prototype PAR-1. Investigation of PAR-1-induced signaling has been shown to be very important in clarifying thrombin's role in cell metabolism, differentiation, and growth. We evaluated connection of PAR-1 with the cAMP/PKA pathway in SNB-19 glioblastoma cells. Alpha-thrombin and the synthetic PAR-1 agonist SFLLRN stimulated PKA as shown by increased PKA activity and translocation of the catalytic PKA alpha subunits (PKA(cat)alpha) into the nucleus. However, no effect on cAMP could be observed. PKA(cat)alpha was found to be associated with nuclear factor-kappa B (NF-kappaB) p65 and its inhibitor protein IkappaB in SNB-19 cells. After PAR-1 stimulation, this association was markedly diminished. We conclude that PAR-1 mediates PKA activation without altering cAMP levels but includes NF-kappaB-associated PKA(cat)alpha in SNB-19 glioblastoma cells. This is the first evidence for a cAMP-independent PKA signaling by a G protein-coupled receptor.

Active Transport, Cell Nucleus↗
PubMed2000

Meizothrombin, an intermediate of prothrombin activation, stimulates human glioblastoma cells by interaction with PAR-1-type thrombin receptors.

Thrombin induces well-characterized effects on normal and neoplastic brain cells by interaction with protease-activated receptor (PAR)-type thrombin receptors. However, nothing is known about the function of intermediate enzymes of prothrombin activation recently shown to evoke PAR-1-mediated signaling in smooth muscle cells. Therefore, we investigated the effect of recombinant human meizothrombin (rMT), one of thrombin's catalytically active precursor enzymes in the prothrombin cleavage cascade, on calcium mobilization in human SNB-19 glioblastoma cells. By using reverse-transcription polymerase chain reaction, immunofluorescence studies with a monoclonal anti-PAR-1 antibody and calcium measurements, SNB-19 cells were shown to express functional PAR-1-type thrombin receptors. PAR-1 is not only a receptor for thrombin in SNB-19 cells but was also activated by rMT very effectively. Under the conditions used in our experiments, SNB-19 cells stimulated with thrombin after rMT challenge were unable to elicit a new calcium response and vice versa. In addition, both rMT and thrombin induced no further calcium signal after that observed with the PAR-1-activating peptide SFLLRN. Therefore, rMT and thrombin seem to activate calcium signaling by similar mechanisms including PAR-1. Our results demonstrate rMT as a potent activator of PAR-1-type thrombin receptors in SNB-19 glioblastoma cells, suggesting a function of catalytically active thrombin precursor enzymes in cells of glial origin.

Calcium↗
PubMed2000

The two-receptor system PAR-1/PAR-4 mediates alpha-thrombin-induced [Ca(2+)](i) mobilization in human astrocytoma cells.

The proteinase-activated receptor 1 (PAR-1) was characterized as a functional receptor for thrombin in cells from different brain tumor entities. Whether PAR-1 alone accounts for thrombin-induced effects in human cancer cells, or whether other PAR contribute is unknown. We established primary cultures from two neurosurgically removed human astrocytomas and investigated intracellular signaling roles of PAR-1 and PAR-4 by estimating the effect of alpha-thrombin and PAR-activating peptides on [Ca(2+)](i) mobilization in single astrocytoma cells. alpha-Thrombin or the PAR-1-activating peptide SFLLRN induced a transient calcium mobilization. This suggests the involvement of PAR-1 in alpha-thrombin-induced calcium signaling in human astrocytoma cells. In addition, a second, PAR-4-dependent, mechanism exists. This was deduced from the findings that a further calcium signal could be observed in human astrocytoma cells stimulated with alpha-thrombin after SFLLRN and the PAR-4-activating peptide GYPGQV also induced a calcium response. In addition, the observation that trypsin, known to activate both PAR-2 and PAR-4, but not the specifically PAR-2-activating peptide SLIGRL induced calcium signaling is a further indication of functional PAR-4-type thrombin receptors in human astrocytoma cells. This is the first report demonstrating a signaling role for a dual thrombin receptor system in human tumor cells.

Apoptosis Regulatory Proteins↗
PubMed2000

Cloning, expression, and characterization of DNA polymerase I from the hyperthermophilic archaea Thermococcus fumicolans.

The DNA polymerase I gene of a newly described deep-sea hydrothermal vent Archaea species, Thermococcus fumicolans, from IFREMERS's collection of hyperthermophiles has been cloned in Escherichia coli. As in Thermococcus litoralis, the gene is split by two intervening sequences (IVS) encoding inteins inserted in sites A and C of family B DNA polymerases. The entire DNA polymerase gene, containing both inteins, was expressed at 30 degrees C in E. coli strain BL21(DE3)pLysS using the pARHS2 expression vector. The native polypeptide precursor of 170kDa was obtained, and intein splicing as well as ligation of the three exteins was observed in vitro after heat exposure. The recombinant enzyme was purified and some of its activities were characterized: polymerization, thermostability, exonuclease activities, and fidelity.

Cloning, Molecular↗
PubMed2000

Different signaling pathways are involved in CCK(B) receptor-mediated MAP kinase activation in COS-7 cells.

Recently, the involvement of the MAP kinase ERK in mitogenic signaling of cholecystokininB (CCK(B)) receptors has been shown. However, the intracellular effector systems involved in this signaling pathway are poorly defined. In this study, we used COS-7 cells transiently transfected with the human CCK(B) receptor to investigate cholecystokinin-induced MAP kinase activation. CCK-8 induced activation of ERK2 which is associated with its phosphorylation and localization in the nucleus. The CCK-8-dependent ERK stimulation is sensitive to wortmannin an inhibitor of phosphoinositide 3-kinases (PI3Ks) indicating the involvement of PI3K activity. To identify the PI3K species involved in mitogenic signaling of the CCK(B) receptor several dominant-negative mutants of PI3K regulatory and catalytic subunits were transiently expressed. Surprisingly, different catalytically inactive mutants of the G protein-sensitive PI3Kgamma did not affect ERK stimulation induced by CCK, whereas a dominant-negative mutant of the regulatory p85 subunit induced significant inhibition of CCK-dependent ERK activity. These results indicate an involvement of PI3K class 1A species alpha, beta or/and delta in signal transduction via CCK(B) receptors. In addition, protein kinase C (PKC)-dependent signaling pathways contribute to CCK(B)-mediated MAP kinase signaling as shown by inhibition of CCK-8-induced ERK activation by the PKC inhibitor bisindolylmaleimide.

Animals↗
PubMed1999

Presence of the proteinase-activated receptor-2 (PAR-2) in human brain tumor cells--trypsin- and SLIGRL-induced calcium response in primary cultured meningiomas.

This study focused on proteinase-activated receptor-2 (PAR-2) in primary cultured human meningioma cells. Stimulation of these cells with the serine proteinase trypsin resulted in a dose-dependent transient calcium response. Since the specific PAR-2 agonist peptide SLIGRL also induced [Ca2+]i mobilization in human meningioma cells and successive application of SLIGRL and trypsin elicited no new calcium signal we conclude that trypsin-induced calcium signaling is mediated by PAR-2 in human meningioma cells. To our knowledge, this is the first report describing functional PAR-2-type receptors in human brain tumor cells.

Brain Neoplasms↗
PubMed1999

PAR 1-type thrombin receptors are involved in thrombin-induced calcium signaling in human meningioma cells.

Thrombin is known to play a role as regulator in tumor spreading and tumor growth. Proteinase-activated receptor 1 (PAR 1)-type thrombin receptors were identified in different cancer cells including human glioblastoma cells. Thus a function of PAR 1 in brain tumors may be suggested. In this study, the presence of PAR 1-type thrombin receptors was investigated in primary cell cultures established from operated human meningiomas from two 59- and 79-year-old women. Characterization of PAR 1 on binding level was performed using immunofluorescence studies with the monoclonal anti-PAR 1 antibody Mab 61-1 directed against a domain in the NH2-terminus of PAR 1. These binding sites constitute functional thrombin receptors that are involved in thrombin-induced signaling in human meningioma cells as demonstrated by investigation of alpha-thrombin- and PAR 1-activating hexapeptide (TRAP-6)-induced [Ca2+]i mobilization. To our knowledge, this is the first report demonstrating thrombin-induced intracellular signaling in human meningioma cells mediated by the PAR 1-type thrombin receptor.

Aged↗
PubMed1998

Protein kinase C is involved in cholecystokinin octapeptide-induced proliferative action in rat glioma C6 cells.

Chotecystoknin octapeptide (CCK-8) has been shown to stimulate DNA synthesis in rat glioma C6 cells by activation of CCKB type receptors. However, the signalling pathways contributing to this proliferative action in C6 cells have not been investigated thus far. This study demonstrated that stimulation of rat glioma C6 cells with CCK-8S resulted in activation of protein kinase C isozymes betaI, betaII, gamma and zeta. The participation of protein kinase C in the CCK-8S-induced effect on C6 cell growth was demonstrated by measurement of [3H]thymidine incorporation and estimation of cell number. The data indicate that CCK-8S stimulates growth in rat glioma C6 cells by a protein kinase C-dependent mechanism.

Animals↗
PubMed1994

[Ultrasound diagnosis of isolated aplasia of the septum pellucidum].

Absence of the septum pellucidum may occur as an isolated malformation. Some of the common paediatric ultrasound and radiology textbooks mention this anomaly. However, only 12 case reports have been published so far. Absent septum pellucidum is also seen in combination with other cerebral malformations like septo-optic pituitary dysplasia (SOPD, de Morsier), agenesis of corpus callosum, holoprosencephaly etc. More often it is seen as a secondary injury due to an increasing internal hydrocephalus. Occurrence of this aplasia and its significance are often underestimated. At a paediatric centre in Germany the anomaly is expected to occur in 1: 1,000 to 1:3,000 cerebral ultrasound examinations. After a review of the literature four cases are presented. All of them were observed by ultrasound during the neonatal period. Using ultrasonography diagnosis of the isolated absence of septum pellucidum can be easily performed by the experienced physician, and will usually be of eminent relevance for the patient.

Diseases in Twins↗
PubMed1992

Tissue expansion in pig skin--a histochemical approach.

In the present study, a porcine model for controlled skin expansion was investigated to improve our understanding of epidermal and vascular responses following stretching. The model is of outstanding importance not only for the clinical use of tissue expansion but provides interesting data for skin physiology and oncology, too. Thirteen out of 15 animals, who underwent silicone tissue expander implantation showed good clinical results. In all of them, skin biopsies were taken at the end of a controlled tissue expansion procedure (final expander volumes 350 or 500 ccm): one tissue specimen was obtained from the centre of the expanded skin area and a second from the neighbouring but nonexpanded skin. The tissue specimens were immediately frozen in liquid nitrogen and processed to 4 microns thick acetone-fixed frozen sections. Lectin histochemistry and immunohistology were performed using the following techniques: direct and indirect immunofluorescence technique (DIFT, IIFT), immunoperoxidase technique (POX) with either 3,3'-diamino-benzidine (DAB) or 3-amino-9-ethyl-carbazole (AEC). The histochemical findings were supplemented by measurements of the number of vital epidermal cell layers, the epidermal thickness (microns), and the papillary vascular count per visual field. There was a significant diminuation of the vascular count (mean +/- S.D. = 55.0% +/- 12.5%; U-test: p less than 5%). By immunohistochemistry, a loss of the basal cell reactivity for the following antibodies was noted: ACAM (against calmodulin), K 8.12 (against keratins 13 +/- 16) and A51-B/H4 (against keratins 8, 14, 18). There was a remarkable increase of filaggrin expression in the uppermost spinal cell layers in expanded skin, which was most pronounced in those specimens with the shortest interval to the last fluid injection into the expander. We gained no evidence for alterations of the expression of suprabasal epidermal keratins, lectin binding sites (UEA I, PNA, ConA, WGA), and vascular lectin- and immunoreactivity due to tissue expansion. The subdermal capsule, which had formed around the silicone expander, was strongly vimentin-reactive. In conclusion, controlled tissue expansion is capable to change the basal cell phenotype--a feature which is shared with a number of conditions with increased proliferative activity and with the epidermis covering different skin tumours. The regular expression of suprabasal keratins and epidermal lectin binding sites provides evidence for a normal epidermal cell differentiation. Furthermore, the porcine skin is a reliable model for studying physiology and pathophysiology of human skin.

Animals↗
PubMed1992

[Experimental studies on tissue expansion in reconstructive surgery].

In the present study, a porcine model for controlled tissue expansion was investigated under the conditions or formation of extreme enlarged randomized flaps. The circulatory disturbances and necrotizing processes to be expected were evaluated immediately after flap formation by intravenous injection of fluorescein dye to predict the surviving area. Lectin histochemistry and immunohistology were performed using either the direct and indirect immunofluorescence technique (DIFT, IIFT) or immunoperoxidase techniques (POX). Over all, the expanded randomized flaps healed without complications in all animals. The acute randomized flaps showed clear necroses already after 10 days. In the thoracic area they averaged 60.3% (SD = 8.17%) and in the pelvic area 47.32% (SD = 14.11%) of the flap. The use of the fluorescein dye test in the present experiment demonstrated that the flap surviving area is significantly greater than the flap staining area. The regular expression of suprabasal keratins and epidermal lectin binding sites provides evidence for a normal epidermal cell differentiation.

Animals↗
PubMed1990

[Circular intrathoracic tracheal replacement by a devitalized artery in the dog].

Prepared artery (origin: human, calf, dog) with external or internal teflon-spiral-supporting was implanted in dogs (n = 10) as a circular intrathoracic tracheal substitute after cross-resection. Human arteries were rejected (n = 2). Calf arteries (n = 5) and dog arteries (n = 3) were incorporated fibrously. Central granulations appeared. The longest survival time was 36 days.

Animals↗
PubMed1990

[Comparative experimental animal studies for testing the usefulness of formalin- and glutaraldehyde-pretreated umbilical cord veins as artery replacements].

Formalin-fixed (F) and glutaraldehyde-pretreated (G) umbilical veins (n = 24) were interposed in the infra-renal aorta of dogs. The follow-up period was 1 year. Early complications with significant differences included 2 occlusions and 3 deaths (41.6%) in group F, 1 occlusion and 1 death (16.6%) in group G. Ten animals of group G and 7 of group F were alive at 1 year, 7 transplants of each of both groups were angiographically and macroscopically patent (25%). Four aneurysms (33.3%) existed angiographically and showed good collateral circulation angiographically (25%). Four aneurysms (33.3%) existed angiographically and macroscopically in group F (statistically significant). Histologically, group G was found to have a delayed resorption and an earlier beginning of connective-tissue proliferation as compared to group F. Considering early and late findings, G-pretreatment is preferable to F-treatment of umbilical veins.

Animals↗
PubMed1989

Restricted cardiovascular and cerebral performance of intra-uterine growth retarded newborn piglets during severe hypoxia.

In 7 term born two-day-old intra-uterine growth retarded (IUGR) piglets cardio- and cerebrovascular, metabolic and EEG reactions were studied at rest and during severe hypoxia in comparison to 17 normal-weight piglets. In IUGR piglets even in control conditions a distinct cerebral blood flow (CBF) elevation, lower cerebrovascular resistance and oxygen consumption in the higher perfused brain regions at diminished arterial blood pressure were observed. Also the arterial glucose concentration was in the borderline hypoglycemic range, however, cerebral glucose delivery was nearly maintained. IUGR piglets survived a 1-h hypoxic period (paO2 = 25-30 mmHg) less frequently. The main reason was the distinctly restricted emergency reaction with a lack of arterial blood pressure increase and blood glucose elevation as well as a reduced (higher perfused brain regions) or absent CBF increase (lower perfused brain regions). Thereby, even in the early stage of hypoxia cerebral oxygen delivery in both brain compartments and oxygen consumption in the latter were decreased followed by a further decrease of the arterial blood pressure. The latter factor was essential for acute cardio-vascular-cerebral insufficiency.

Animals↗