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W Leitner

Publications and source records attributed to W Leitner.

At least 19 recordsLinked to original sources
PubMed2000

Steel-promoted oxidation of olefins in supercritical carbon dioxide using dioxygen in the presence of aldehydes

Oxidation of olefins occurs effectively in supercritical carbon dioxide as the reaction medium with dioxygen as the primary oxidant and aldehydes as sacrificial co-oxidants. No catalyst is required, but the reaction is promoted by the stainless steel of the reactor walls. Depending on the substrate, vinylic oxidation or epoxidation can be the prevailing pathway. Epoxidation is particularly effective for substrates with internal double bonds and for long-chain terminal olefins.

Journal Article↗
PubMed2000

Mechanistic aspects of dihydrogen activation and transfer during asymmetric hydrogenation in supercritical carbon dioxide.

A new "CO2-philic" chiral rhodium diphosphinite complex was synthesized and applied as catalyst precursor in the asymmetric hydrogenation of dimethyl itaconate in scCO2, scC2H6 and various liquid organic solvents. Deuterium labeling studies and parahydrogen-induced polarization (PHIP) NMR experiments were used to provide the first detailed mechanistic insight into the activation and transfer of the dihydrogen molecule during hydrogenation in scCO2. Chemical interactions between CO2 and reactive intermediates of the catalytic pathway could be excluded as possible explanations for the experimentally verified difference in the catalytic behavior in scCO2 and hexane.

Carbon Dioxide↗
PubMed1998

[Confiscation and delivery of patient records].

In most cases, a physician faces an investigation by a prosecutor the first time when his office is subject of a search or confiscation. Without warning in advance, the police or the prosecutor usually demands the delivery of patients records with or without a search warrant. This paper demonstrates the legal requirements for a search and offers recommendations about behavior.

Confidentiality↗
PubMed1997

The effect of antigen stimulation on splenic transplants.

The present paper deals with the regeneration of splenic tissue after autologous transplantation. Control and transplanted rats (60 days after operation (10(6) cells per injection). The effect of a primary response was studied by a single injection, long-lasting bacteraemia was imitated by 5 injections in weekly intervals. Spleens and transplants were investigated by flow-cytometry and immunohistochemistry. Additionally, the proliferation activity and the specific antibody production against Escherichia coli proteins were tested. Flow-cytometric analysis showed altered behaviour of T-helper cells and B-cells in transplants following a primary response, whereas in the multiple injection group a difference between the splenic and transplant response was restricted to macrophages and MHC II+ cells. The results of the morphometric analysis revealed that the cellular composition of unstimulated transplants was very similar to that of the spleen with some subtle alterations. Only the marginal zone showed more striking differences concerning the homing of several cell classes. Under stimulatory conditions, these subtle alterations became more drastic so that CD5+ cells, B-cells and macrophages responded in an abnormal manner in both groups. The analysis of thymidine kinase disclosed decreased activity in the spleen after weekly antigen stimulation. The stimulation index of all transplant groups was significantly lower than that of the spleen. The specific antibody (IgG) production after a single immunization was highest in the transplant group. All groups responded after the multiple challenge. In conclusion, the results demonstrate that splenic transplants differs in several, but subtle aspects from normal splenic tissue. The main reason for most of these alterations may be a slightly misguided recirculation and/or homing of cells.

Animals↗
PubMed1996

Insulin stimulates mitogen-activated protein kinase by a Ras-independent pathway in 3T3-L1 adipocytes.

To characterize tissue-specific differences in insulin signaling, we compared the mechanisms of mitogen-activated protein (MAP) kinase activation by insulin in the mitogenically active 3T3-L1 fibroblasts with the metabolically active 3T3-L1 adipocytes. In both cell lines, insulin significantly increased p21(ras).GTP loading (1.5-2-fold) and MAP kinase activity (5-8-fold). Inhibition of Ras farnesylation with lovastatin blocked activation of p21(ras) and Raf-1 kinase in both 3T3-L1 fibroblasts and 3T3-L1 adipocytes. In 3T3-L1 fibroblasts, this was accompanied by an inhibition of the stimulatory effect of insulin on MAP kinase. In contrast, in 3T3-L1 adipocytes, despite an inhibition of activation of p21(ras) and Raf-1 by lovastatin, insulin continued to stimulate MAP kinase activity. Fractionation of the cell lysates on the FPLC Mono-Q column revealed that lovastatin inhibited insulin stimulation of ERK2 (and, to a lesser extent, ERK1) in 3T3-L1 fibroblasts and had no effect on the insulin-stimulated ERK2 in 3T3-L1 adipocytes. These results demonstrate an important distinction between the mechanism of insulin signaling in the metabolically and mitogenically active cells. Insulin activates MAP kinase by the Ras-dependent pathway in the 3T3-L1 fibroblasts and by the Ras-independent pathway in the 3T3-L1 adipocytes.

Adipocytes↗
PubMed1996

Interactions of protein kinase C with insulin signaling. Influence on GAP and Sos activities.

In this study, we investigated the influence of the protein kinase C (PKC)-dependent system upon the ability of insulin to stimulate p21(ras).GTP loading in 3T3-L1 adipocytes. Activation of PKC by 12-0-tetradecanoylphorbol-13-acetate (TPA) did not affect the basal amount of p21(ras).GTP but significantly reduced insulin-induced increases in p21(ras).GTP. This reduction was due to inhibition of the insulin's ability to stimulate guanine nucleotide exchange activity of Sos in cells incubated with 100 nM TPA for either 30 min or 3 h. TPA had no effect on basal activity of Sos. Depletion of PKC by an 18-h incubation with TPA or inhibition by bisindolylmaleimide resulted in profound inhibition of the insulin-induced p21(ras).GTP loading. In contrast to PKC activation, removal of PKC did not influence Sos activity but resulted in a 2-fold stimulation of GTPase activating protein (GAP). This effect of PKC depletion is unique to 3T3-L1 adipocytes and was not observed in either 3T3-L1 fibroblasts or Rat-1 fibroblasts. Thus, it appears that in 3T3-L1 adipocytes, PKC has a constitutive inhibitory effect on GAP that permits insulin to activate Sos and p21(ras). Removal of this inhibitory influence activates GAP and reduces insulin-stimulated p21(ras).GTP loading.

3T3 Cells↗
PubMed1996

Safety, immunogenicity, and efficacy of Plasmodium falciparum repeatless circumsporozoite protein vaccine encapsulated in liposomes.

Seventeen malaria-naive volunteers received a recombinant Plasmodium falciparum vaccine (RLF) containing the carboxy- and the amino-terminal of the circumsporozoite protein (CSP) antigen without the central tetrapeptide repeats. The vaccine was formulated in liposomes with either a low or high dose of 3-deacylated monophosphoryl lipid A (MPL) and administered with alum by intramuscular injection. Both formulations were well tolerated and immunogenic. MPL increased sporozoite antibody titers measured by ELISA, Western blot, and immunofluorescence assay. One high-dose MPL vaccine formulation recipient developed a CSP-specific cytotoxic T lymphocyte response. After homologous sporozoite challenge, immunized volunteers developed patent malaria. There was no correlation between prepatent period and antibody titers to the amino- or carboxy-terminal. The absence of delay in patency argues against inclusion of the amino-terminal in future vaccines. A significant cytotoxic T lymphocyte response may have been suppressed by the inclusion of alum as an adjuvant.

Adolescent↗
PubMed1995

Signal transduction pathways leading to insulin-induced early gene induction.

We examined the signal transduction pathway leading to insulin stimulation of two immediate early genes, c-fos, and the early growth response gene, Egr-1. In Rat 1 fibroblasts overexpressing normal human insulin receptors (HIRc-B), insulin and IGF-I rapidly and transiently induced the expression of both c-fos and Egr-1 mRNA with maximum accumulation at 30 min, declining to basal levels at 120 min. Insulin (100 ng/mL) increased c-fos and Egr-1 mRNA expression 10-fold (EC50 = 20 ng/mL), whereas IGF-I (100 ng/mL) and serum (20%) led to a 3- and 11.5-fold increase, respectively. Insulin-stimulated c-fos protein expression was maximal at 1 h postinduction and undetectable at 4 h. The effects of insulin and IGF-I on both c-fos mRNA and protein expression were absent in Rat 1 fibroblasts expressing tyrosine kinase-defective human insulin receptors (A/K1018). In cells expressing insulin receptors in which the two C-terminal tyrosines are mutated to phenylalanine (Y/F2 cells), the insulin stimulated increase in Egr-1 and c-fos mRNA was comparable to that of HIRc cells, whereas, in cells expressing C-terminal truncated receptors (delta CT cells), the insulin induced increase in Egr-1 mRNA was normal, but the c-fos mRNA response was severely blunted. As expected, the insulin effect to increase ras GTP formation and MAP kinase activity was negligible in A/K1018 cells but normal, or supernormal, in Y/F2 cells. Importantly, stimulation of ras GTP was increased in delta CT cells, whereas stimulation of MAP kinase activity was almost absent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Regeneration of splenic stromal elements.

Splenic regeneration represents an interesting phenomenon both in relation to its role as a model system (to study the development of the complex three-dimensional architecture of an immunological organ) and because of the clinical application, namely autotransplantation of spleen. The latter is one of the attempts to restore splenic functions after splenectomy, which is known to increase a life-long risk of fatal sepsis. However, splenic functions of autotransplanted splenic tissue are known to be highly dependent on the recovery of the complex microenvironment and immunoarchitecture of the splenic compartments during the regeneration processes, but the elements inducing splenic reorganization are still unknown. Therefore, the present work investigates whether splenic stroma depleted of cells is able to induce regenerative processes after implantation. In addition, we tried to recombine stromal tissue with selected cell populations to study their influence. Cell-free stromal tissue induced angiogenesis and to a lesser extent also attracted the immigration of lymphocytes during the first 60 days of regeneration. However, after this period of regeneration, the transplants began to degenerate and were resorbed. The recombination of stromal tissue with mitogen-stimulated spleen cells only resulted in intensifying the degenerative processes, and all implants were resorbed after 120 days. Except that in the first 30 days there were some accumulations of lymphocytes that resembled primitive follicles, no splenic compartments such as red pulp, periarteriolar lymphoid sheath, or marginal zone could be detected in any of the transplants. From these results it can be concluded that splenic stroma can induce the primary events of splenic regeneration (like angiogenesis), but is not able to provide an appropriate microenvironment and immunoarchitecture for a correct repopulation and differentiation of cells. Furthermore, the recombination experiments point to a minor role of T-cells and possibly an important role for accessory cells in splenic regeneration.

Animals↗
PubMed1994

Evidence that p21ras mediates the neurotrophic effects of insulin and insulin-like growth factor I in chick forebrain neurons.

Insulin and insulin-like growth factors (IGF-I and IGF-II) support the survival and differentiation of many types of neurons, including those from fetal chick forebrain. The mechanisms by which these peptides exert their neurotrophic actions are poorly understood. The aims of this study were to determine if insulin and IGF-I activate p21ras in fetal chick forebrain neurons and if activation of p21ras mediates the neurotrophic actions of these peptides. Activation of neuronal p21ras was examined by measuring the amount of GTP bound to p21ras before and after growth factor treatment. Insulin and IGF-I increased the ratio of GTP/GTP + GDP by 31 +/- 9.0% and 36 +/- 8.0%, respectively, p21Ras activation by insulin and IGF-I was maximal within 5 min. In the presence of insulin the response was sustained out to 180 min, whereas the response to IGF-I decreased significantly by 180 min. Both peptides stimulated p21ras at low concentrations with a maximal response obtained at 10 ng/ml for each peptide, idicating that insulin and IGF-I activate ras by interacting with their homologous receptor. Pretreatment of neurons with lovastatin (2 micrograms/ml), an inhibitor of ras isoprenylation, completely blocked the activation of p21ras by insulin and IGF-I. Lovastatin also blocked the ability of these growth factors to support the survival and differentiation of fetal chick neurons in culture. We conclude that insulin and IGF-I activate p21ras in fetal chick forebrain neurons by increasing the amount of GTP bound to p21ras. The activation of neuronal p21ras is necessary for insulin and IGF-I to promote survival and differentiation in these neurons.

Animals↗
PubMed1993

GLUT-4 phosphorylation and its intrinsic activity. Mechanism of Ca(2+)-induced inhibition of insulin-stimulated glucose transport.

In this study, we examined the influence of high levels of cytosolic calcium on phosphorylation status and function of GLUT-4 in isolated rat adipocytes. Intracellular calcium was elevated by exposing adipocytes to either extracellular ATP (1.6 mM) or thapsigargin (100 nM). Both agents increased cytosolic calcium 2-3 fold. While basal glucose uptake was unaffected, both ATP and thapsigargin reduced insulin-stimulated glucose transport by 40-70% (p < 0.05). Neither ATP nor thapsigargin affected GLUT-4 content or its translocation from the low density microsomes to the plasma membrane (PM). In contrast, GLUT-4 immunoprecipitated from the PM of adipocytes exposed to either ATP or thapsigargin was phosphorylated to a greater extent than the GLUT-4 isolated from control cells. ATP and thapsigargin also abolished insulin-stimulated dephosphorylation of GLUT-4. At the same time, GLUT-4 intrinsic activity was significantly reduced in adipocytes with high levels of cytosolic calcium (p < 0.05). Preincubation of adipocytes with cAMP antagonist, RpcAMP (10(-4) M), and calcium channel blocker, nitrendipine (30 microM), improved the ability of insulin to dephosphorylate GLUT-4 and restored insulin-stimulated GLUT-4 intrinsic activity. We conclude that elevated levels of cytosolic calcium interfere with insulin's ability to dephosphorylate GLUT-4, thus reducing its intrinsic activity.

Adenosine Triphosphate↗
PubMed1992

Regeneration of autotransplanted splenic tissue at different implantation sites.

Inbred animals (Lewis rats) were used to investigate the regeneration of autologously implanted splenic tissue at intra-omental and subcutaneous sites. Quantitative immunohistology with monoclonal antibodies against lymphocytes and macrophages was performed to analyse the cell density of red pulp (RP), periarteriolar lymphoid sheath (PALS), marginal zone (MZ) and follicle, 7-180 days after transplantation. Antigenic, allogeneic and mitogenic stimulation and Northern blotting were also performed. Transplant groups differed from spleen only in the reduced size of PALS; however, quantitative analysis demonstrated subtle differences between spleen and transplants. The cell density of B-cells and ED-1+ macrophages was reduced in the RP, Tsupp/cyt-cells were decreased and B-cells increased in PALS, and B-cells and Thelper-cells reduced in the MZ. No differences could be detected between the transplant groups. Flow-cytometric analysis of cell suspensions from spleen and transplants revealed a reduction of T-cells (OX-19+), MHC-I and transferrin-receptor-bearing cells in both transplant groups, and a decrease in the number of Thelper-cells and ED-3+ macrophages in subcutaneous transplants. Both transplant groups were defective regarding the allogeneic and pokeweed mitogen response. Aberration of the lipopolysaccharide response was restricted to subcutaneous transplants, which additionally showed abnormal expression of interferon-gamma, interleukin-5 and interleukin-6 mRNA. Thus, subtle alterations of the newly developed microenvironment and/or lymphocyte-homing may influence the regeneration of splenic tissue; the implantation site may represent an important parameter in functional reorganisation.

Animals↗
PubMed1992

Immunoarchitecture and specific functions of splenic autotransplants at different implantation sites.

The present study deals with the morphological and functional development of intraomentally and subcutaneously implanted splenic tissue. Spleens and splenic transplants from 138 Lewis rats were investigated with immunohistological, immunological and molecular biological methods at different times after operation (up to 200 days postoperatively). The analysis of the development revealed a nonsignificant reduction concerning the weight of subcutaneous replants and a nonsignificant decrease of the weight of female transplants of both groups at different phases after operation. The cell composition of cell suspensions from spleen and both transplant types showed a deficiency of T, B, MHC-I+ cells and a certain macrophage subset (ED-3+ cells) in transplants. In a quantitative immunohistological analysis of compartments (red pulp, periarteriolar lymphoid sheaths, marginal zone and follicles) the T cell reduction was related to the Tsupp/cyt cells and T cell receptor bearing cells in the periarteriolar lymphoid sheaths, whereas the density of T helper cells was normal. In addition, a different homing of kappa-light chain positive and leukocyte common antigen (B cell type)-positive B cells in follicles and marginal zone was detected. The amount of two macrophage subsets (ED-1+ and ED-2+ cells) was increased in the red pulp. Only minor differences in the immunoarchitecture of transplants at different implantation sites were measured. A functional analysis of spleen compared to both transplant groups elicited a B cell defect after LPS stimulation in subcutaneous transplants and a reduced allogeneic response of both transplant types but a normal proliferation of T cells after ConA stimulation and a correct IgM antibody response against sheep red blood cells. The in vivo mRNA expression and the expression kinetics of interferon-gamma and granulocyte-macrophage colony-stimulating factor after antigen stimulation differed in both transplant groups with a remarkable permanent expression of both mediators in subcutaneous transplants. It can be summarized that the results clearly indicate a development of spleen-like immunoarchitecture of intraomental replants with subtle cellular, functional and molecular alterations. In contrast, despite a comparable development, some severe functional defects occurred in subcutaneous implants pointing out the important role of interactions between the regenerating splenic tissue and the target tissue on a functional and molecular level.

Abdominal Muscles↗
PubMed1992

[Autotransplantation of the spleen in rats: development, function and cytokine expression in intra-omental and subcutaneous regeneration].

The implantation of splenic tissue at different implantation sites (intraomental and subcutaneous) into one animal (Lewis rats) results in the development of splenic nodules at both sites. In a quantitative immunohistological analysis of splenic compartments such as red pulp (RP), periarteriolar lymphoid sheaths (PALS), marginal zone (MZ) and follicles (F) the T-cell reduction was related to the T(helper) cells in the MZ and T(supp/cyt) cells in the PALS. In contrast, the cell density of B cells and ED-1+ macrophages in the PALS and T(supp/cyt) cells in the MZ was increased. Significant differences between the implantation sites were restricted to CD5+ cells (thymocytes and T cells) in the MZ and OX-33+ cells (B cells with LCAB antigen) in the PALS. The reorganisation of the compartments of subcutaneous implants showed a delay of one week as compared with omental ones. Functional assays like haemolytic plaque assay, mitogen stimulation and mixed lymphocyte assay elicited an analogous delay of the functional maturation of IgM-positive B cells, a reduced proliferation of both transplant groups after pokeweed mitogen (PWM) stimulation, a decreased response after lipopolysaccharide (LPS) stimulation in solely subcutaneous replants and no differences concerning the mitogens concanavalin A (ConA) and phytohaemagglutinin (PHA). Both transplant groups showed a significantly reduced allogeneic response. The results of the functional analysis and the abnormal mRNA expression of Il-5, Il-6 (Interleukin 5 and 6), GMCSF (Granulocyte-Macrophage-Colony-Stimulation-Factor) and IFN-gamma (Interferon gamma) in subcutaneous replants indicate subtle molecular alterations (independent of a spleen-like immunoarchitecture) at this site.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Gene expression of type I phospholipase A2 in pancreatic beta cells. Regulation of mRNA levels by starvation or glucose excess.

Messenger RNA from intact rat pancreatic islets, or from transformed hamster beta (HIT) cells, hybridized with the cDNA probe for type I (but not type II) phospholipase A2. The levels of phospholipase A2 mRNA increased in islets from fasted rats; they decreased in islets cultured in a high glucose concentration (control values at 5.5 mM glucose = 150 +/- 6% of those at 22 mM) which impaired subsequent insulin secretion (reduction in second-phase release = 70 +/- 11%). These studies uniquely demonstrate that type I phospholipase A2 is expressed specifically in beta cells and that nutrient availability modulates transcript levels, an effect which could that nutrient availability modulates transcript levels, an effect which could contribute to the detrimental influence of prolonged hyperglycemia on islet function.

Animals↗
PubMed1981

Influence of an antiarrhythmic premedication on the development of premature ventricular contractions during fiberoptic gastroduodenoscopy.

Heart rate, blood pressure and ECG changes during fiberoptic gastroscopy were examined in 128 patients, 60 of whom had been orally premedicated with Mexiletine. 55% of the non-premedicated patients developed occasional, and 22% of this group developed accumulated or frequent, premature ventricular contractions. In the patient group with antiarrhythmic premedication, the respective figures were 25% and 8%, and in this group patients with a normal ECG developed premature ventricular contractions less frequently than patients with pathological changes in the ST segment. The antiarrhythmic premedication had no influence on pulse or blood pressure.

Arrhythmias, Cardiac↗