Biomedical subjects
J Bauer
Publications and source records attributed to J Bauer.
[Treatment of acute low cardiac output syndrome after surgery of congenital heart defects: value of enoximone].
Children undergoing cardiac surgery are at additional risk for postoperative low cardiac output syndrome (LCOS). Anticipation of the syndrome from preoperative hemodynamic condition, surgical procedure, and adverse intraoperative events is a key to successful postoperative management. Inotropic support is primarily based on catecholamines. However, uncoupling of human cardiac beta-adrenoceptors during cardiopulmonary bypass with cardioplegic cardiac arrest may be the reason why many patients respond only weakly to beta-adrenoceptor agonists. Phosphodiesterase (PDE) inhibitors act by reducing intracellular breakdown of cAMP, which is elevated independently from beta-receptors. The use of PDE-inhibitors might be advantageous in patients with uncoupled beta-adrenoceptors, as occurs after cardiopulmonary bypass. In addition, PDE-inhibitors can prevent further downregulation of the adrenoceptors due to avoiding prolonged therapy by beta-agonists. In this context, the addition of enoximone, a PDE-inhibitor, to adrenergic agents has been found useful in increasing cardiac output in children with catecholamine-resistant LCO, as well as in children with compensated hemodynamics during catecholamine therapy.
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[Conservative surgical treatment of breast carcinoma in women from the viewpoint of the oncologist-radiotherapist].
The authors draw attention to the changed approach to treatment of initial stages of breast in women--a change from radical mastectomy to less radical operations supplemented by radiotherapy or possibly systemic treatment. They analyze in detail the prerequisites and results of this procedure and demonstrate their conclusions on a group of 27 women.
Defective vasculature in fibronectin-receptor-deficient CHO cell tumors in nude mice.
The level of expression of the alpha 5/beta 1 integrin fibronectin receptor (FnR) strongly affects the growth rate of CHO cell tumors in nude mice. Here we report that alpha 5/beta 1 expression also influences the organization of the tumor vasculature. Tumors formed from CHO clones defective in FnR expression have a leaky vasculature that gives them a hemorrhagic appearance. Tumors from wild-type CHO cells, or from FnR-deficient CHO clones transfected with constructs coding for the alpha 5 integrin subunit, have an intact, non-leaky vasculature. In tumors from FnR-deficient cells, the endothelial lining of blood vessels is sparse, and red cells and plasma proteins can be detected in the tumor parenchyma. In tumors from cells expressing the alpha 5/beta 1 FnR, tumor vessels are circumscribed by a lining of von-Willebrand-factor-positive endothelial cells, and blood cells and proteins are confined to the vessel lumina. Thus, the level of expression of the alpha 5/beta 1 FnR in the tumor parenchymal cells can influence the development of tumor vasculature. Since alpha 5/beta 1 is vital to the organization of the extracellular matrix, one possibility is that altered matrix assembly contributes to the defective vascularization seen in alpha 5/beta 1-deficient tumors.
Expression of low-affinity NGF receptor and trkB mRNA in human SH-SY5Y neuroblastoma cells.
We have used the human neuroblastoma cell line SH-SY5Y as a model system to investigate the expression and regulation of the receptors for brain-derived neurotrophic factor (BDNF), a member of the nerve growth factor (NGF) family of neurotrophins. We demonstrate that SH-SY5Y cells express transcripts encoding the low-affinity NGF receptor (LNGFR) and trkB, the signal transducing receptor unit for BDNF. Interaction of BDNF with SH-SY5Y cells increased the transcription of the c-fos gene, showing that these molecules encode functional BDNF receptors. Our findings that differentiating agents such as retinoids and cAMP analogs increased the expression of LNGFR, but decreased trkB mRNA levels, suggest that LNGFR and trkB have different roles during neuronal differentiation.
Expression of an outwardly rectifying K+ channel in rat microglia cultivated on teflon.
Membrane currents of cultured human monocytes and rat microglia were recorded with the whole-cell patch clamp technique. Freshly isolated monocytes or resting (proliferating) microglia express only inwardly rectifying K+ channels. However, incubation in teflon bags leads to the expression of additional, outwardly rectifying K+ channels. The outward K+ conductance of microglial cells was inhibited by intracellular Cs+ and extracellular 4-aminopyridine or tetraethylammonium. Functional similarities with the microglial outwardly rectifying K+ channel were found in the Kn-channel of lymphocytes which has recently been cloned (RGK5). The polymerase chain reaction (PCR) was used to demonstrate the presence of RGK5-like mRNA in microglia.
Influence of phenytoin on cytoskeletal organization and cell viability of immortalized mouse hippocampal neurons.
Phenytoin (PHT) is a commonly used anticonvulsant drug; several side effects have been described, including morphological changes in brain cortex and cerebellar neurons and teratogenic lesions in infants of epileptic mothers. Evidence of other authors indicate that PHT may exert its action through the modification of phosphorylation patterns of cytoskeletal polypeptides. We have studied the influence of the anticonvulsant drug phenytoin on immortalized mouse hippocampal neurons in culture. This was done by means of MTT-assays, immunocytochemical and immunoblot analyses, measurements of cell metabolism, measurements of the length of neuronal processes, and electron microscopy. A distinct and pronounced effect of PHT could be characterized with regard to the formation of neuronal processes, involving malfunction of an assembly-mechanism of cytoskeletal constituents. These accumulated within appendages (blebs) or cytoplasmic condensations, instead of forming normally organized processes. However, PHT did not interfere with bulk synthesis of cell proteins and specific cytoskeletal components.
Expression of functional trk protooncogene in human monocytes.
There is increasing evidence that neurotrophins, including nerve growth factor (NGF), exert specific effects on cells of the immune system in addition to their neurotrophic actions. This report shows that human monocytes express the trk protooncogene, encoding the signal-transducing receptor unit for NGF. This receptor is functional, since interaction of NGF with monocytes triggered a respiratory burst, the major component of monocyte cytotoxic activity. During in vitro differentiation of human blood monocytes to macrophages trk expression decreased, suggesting a maturation-dependent trk expression decreased, suggesting a maturation-dependent trk regulation. Treatment of monocytes with Staphylococcus aureus Cowan I, a potent activator of monocytes, stimulated trk mRNA synthesis in a time-dependent way, implying a modulatory role for NGF in immune functions. The finding that dibutyryl cAMP elicited a time-dependent trk induction in monocytes as well as in phorbol ester-differentiated promonocytic U937 cells indicates that adenylate cyclase is involved in monocytic trk regulation. These results suggest that NGF, in addition to its neurotrophic function, is an immunoregulatory cytokine acting on monocytes.
Regulation of eicosanoid biosynthesis in the macrophage. Involvement of protein tyrosine phosphorylation and modulation by selective protein tyrosine kinase inhibitors.
The protein tyrosine kinase (PTK) inhibitor genistein has been demonstrated to inhibit platelet-activating factor-stimulated prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-primed P388D1 macrophage-like cells (Glaser et al., J Biol Chem 265: 8658-8664, 1990). Therefore, the role of PTK in eicosanoid biosynthesis was investigated in murine resident peritoneal macrophages using genistein and tyrphostin-25, selective PTK inhibitors. Genistein, a competitive inhibitor of ATP binding on PTK, inhibited PGE2 production (IC50 = 20 microM) in response to zymosan, calcium ionophore A23187, and phorbol myristate acetate stimulation. Genistein also inhibited leukotriene C4 (LTC4) production in response to zymosan and calcium ionophore A23187 (IC50 = 10 and 15 microM, respectively) stimulation. Tyrphostin-25, a competitive inhibitor of substrate binding on PTK, inhibited zymosan-stimulated PGE2 and LTC4 production, IC50 = 20 and 7 microM, respectively. Neither genistein nor tyrophostin-25 had any effect on human synovial fluid phospholipase A2 (PLA2) activity in vitro or on cyclooxygenase activity in the intact macrophage; however, tyrphostin-25 did affect 5-lipoxygenase activity (determined from the metabolism of exogenously applied arachidonic acid). These results suggest PTK-mediated phosphorylation as a common event in the signal transduction mechanisms of different stimuli which activate PLA2 for arachidonic acid release and subsequent eicosanoid biosynthesis. Immunoblot analyses of zymosan-stimulated peritoneal exudate cells with the phosphotyrosine monoclonal antibody clone 4G10 demonstrated an increase in protein phosphotyrosine levels in eight major protein bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis: p59, 71, 76, 90, 100, 112, 125 and 150. Maximal phosphorylation of these protein substrates occurred after 1-2 min stimulation. Zymosan and LPS stimulation of peritoneal exudate cells produced similar patterns of protein tyrosine phosphorylation. Zymosan-stimulated tyrosine phosphorylation was inhibited by tyrphostin-25 in a concentration-dependent manner between 10 and 60 microM, demonstrating a similar concentration response between effects on tyrosine phosphorylation and eicosanoid biosynthesis in the murine peritoneal macrophage. The use of selective PTK inhibitors suggests a common role for PTK and tyrosine phosphorylation in eicosanoid biosynthesis in the murine peritoneal macrophage.
Immune-complex-trapping cells in the spleen of the oriental fire-bellied toad, Bombina orientalis.
The spleen of the oriental fire-bellied toad, Bombina orientalis, consists of well-developed white pulp, separated from the lymphocytic marginal zone by the connective tissue boundary layer. Injection of peroxidase-conjugated rabbit anti-peroxidase revealed that these immune complexes were localized on the surface of acid-phosphatase-positive and non-specific-esterase-positive cells in the white pulp. The majority of immune-complex-trapping cells were present around the blood vessels. Cell processes of some of these cells penetrated into the wall of blood vessels. The significance of the present findings is discussed with respect to the evolution of immune-complex-trapping cells in the spleen.
Pharmacological characterization of WAY-121,520: a potent anti-inflammatory indomethacin-based inhibitor of 5-lipoxygenase (5-LO)/phospholipase A2 (PLA2).
WAY-121,520 inhibited human synovial fluid PLA2 (HSF-PLA2) (IC50 = 4 microM) using arachidonic acid-labeled E. coli as substrate. Further biochemical characterization of WAY-121,520 demonstrated potent inhibition of 5-lipoxygenase (5-LO) activity in the murine macrophage (LTC4, IC50 = 4 nM) and rat PMN (LTB4, IC50 = 10 nM) and an ability to antagonize LTD4 binding to isolated guinea-pig trachea (pKB = 6.0). In vivo anti-inflammatory activity was noted in murine TPA-induced (ED50 = 91 micrograms/ear) and arachidonic acid-induced (66% inhibition at 400 micrograms/ear) ear edema and in leukotriene-dependent antigen-induced bronchoconstriction in the guinea pig (73% inhibition at 50 mg/kg, p.o.). WAY-121,520 represents a novel series of indomethacin-based inhibitors of PLA2 with anti-inflammatory activity resulting from a combination of biochemical activities (inhibition of 5-LO and PLA2 and LTD4 antagonism). This agent may provide added therapeutic efficacy over more selective inhibitors.
Demonstration of interleukin-1 beta in Lewis rat brain during experimental allergic encephalomyelitis by immunocytochemistry at the light and ultrastructural level.
Interleukin-1 beta (IL-1) is a cytokine which exerts many biological effects during inflammation. In the present study, experimental allergic encephalomyelitis (EAE) was induced in Lewis rats. During the various stages of EAE, the presence of IL-1 in the brain was investigated using immunocytochemistry at both the light and ultrastructural level. Ten days after immunization, IL-1 immunoreactivity was found in brains of animals which at this time showed mild clinical signs. Outside the blood-brain barrier, IL-1 was localized in the cytoplasm of meningeal macrophages and perivascular cells. Within the brain parenchyma, IL-1 immunoreactivity was distributed in perivascular lesions in the cytoplasm of infiltrated macrophages and activated microglia. On day 13, animals had developed a full blown EAE. At this stage the number of lesions with IL-1-positive cells had increased. In the remission phase (day 25), lesions with IL-1-positive cells could still be detected but were less pronounced as compared to day 13. Other presumptive IL-1-producing cell types like endothelial cells or astrocytes were, at none of the various stages, found to stain for IL-1.
Effects of interleukin-1 and interleukin-6 on metallothionein and amyloid precursor protein expression in human neuroblastoma cells. Evidence that interleukin-6 possibly acts via a receptor different from the 80-kDa interleukin-6 receptor.
Since immunohistochemical studies indicated the presence of interleukin-6 in the cortices of patients with Alzheimer's disease, we were interested in the eventual biological effects of this cytokine on neuronal cells. We found that interleukin-6 and interleukin-1 induced metallothionein expression in a human neuronal (SH-SY5Y neuroblastoma) cell line. In contrast to metallothionein, amyloid precursor protein expression was unaffected by both cytokines. When searching in the same cell line for the expression of the classical 80-kDa interleukin-6 binding protein, which is part of the dimeric interleukin-6 receptor, we were unable to detect the respective mRNA. Our findings either indicate that the interleukin-6 receptor in these cells is expressed in extremely low levels or that interleukin-6 may act upon neuronal cells via a different, yet unknown neuronal receptor.
Involvement of T lymphocytes in curative effect of a new immunomodulator OM 163 on rat colon cancer metastases.
In a model of colon cancer in syngeneic rats, a new immunomodulator, OM 163, induced the complete disappearance of peritoneal carcinomatosis (nodules measuring 1-5 mm) in 41 out of 82 rats. Those results were confirmed in a survival experiment in which 3 out of 10 treated rats died free of tumour 10, 18 and 28 months after the tumour cell injection while all the untreated control rats died of their tumours within 3 months. OM 163 had a systemic effect, since injected intraperitoneally it completely inhibited the growth of lung metastases in 13 out of 20 rats. The antitumour effect of OM 163 was also observed in two rat strains on original tumours. Lymphocyte infiltration was observed in the tumours mainly constituted of CD4+ and CD8+ cells. The treatment had no effect in nude rats, confirming the involvement of T lymphocytes. Furthermore, rats cured by OM 163 were protected against a second challenge of tumour cells and in a Winn's assay, splenocytes from cured rats protected normal rats against tumour cells.
Comparative activities of macrolide derivatives on murine listeriosis.
The new macrolide derivatives such as clarithromycin, roxithromycin and azithromycin have only slightly stronger in vitro antibacterial activity on Listeria monocytogenes than the older derivatives such as erythromycin and spiramycin. In vivo, however, the new macrolides exert a much better therapeutic action on murine listeriosis. Among the new derivatives, clarithromycin is the most active. Azithromycin has one characteristic advantage: it is still active several days after cessation of therapy because of its long half-life. This strong therapeutic activity may be due to the known intracellular accumulation of macrolides in macrophages, which is essential for the eradication of intracellular bacteria such as L. monocytogenes. In spite of the strong intracellular accumulation the effector function of the defense system is not impaired, because the course of infection with a macrolide-resistant strain of L. monocytogenes in mice was not enhanced by macrolide treatment.
[Neuropathologic, immunologic and psychobiological aspects of Alzheimer's dementia].
This review attempts a consolidated overview of the results of molecular biological research on amyloid pathology in Alzheimer's disease crosslinked with other aspects of the disease that have not been so much in focus in recent years. The spotlight will be on many pointers to an immunological process as part of the Alzheimer pathology. The problem of the specificity of plaques and of neurofibrillary tangles that both are considered to be classical neuropathological markers of Alzheimer's disease is critically reviewed on the basis of existing findings in neuropathology in non-demented and demented elderly persons. The traditional unidirectional concept that interprets the neuropsychological functions inhibited in Alzheimer's dementia merely as sequels to damaged morphological structures, is questioned. Earlier and more recent experimental findings indicating that dysfunctional and deficient use of neuropsychological functions can inhibit neuronal plasticity and can be the origin of morphological changes, are placed in relation to numerous pointers to non-cognitive mental anomalies prior to the outbreak of Alzheimer's disease. In Alzheimer's dementia, pathology of synapses is preferably correlated with neuropsychological deficits. Findings on this pathology are discussed as a possible expression of a neuronal plasticity decrease that is partly conditioned by psychobiological mechanisms.
[Image quality evaluation and dosage requirements of digital image intensifier radiography].
In the course of a study of the advantages and disadvantages of digital image intensifier radiography, image quality and dose requirements were measured, using a phantom. Spatial resolution was related to exposure parameters, the differentiation of structural details at varying contrast concentrations and the phantom entry doses. Spatial resolution was approximately 1.8-2.0 line pairs/mm (lp/mm) and there was no recognisable effect from increasing the dose or the thickness of the phantom. Additional subsequent edge enhancement led to increased detail recognition up to 2.0 lp/mm. Also, phase inversion of the image (negative image) can improve detail recognition. Radiation dose can be reduced to 15% compared with conventional imaging methods. Digital radiography with image intensifier techniques can therefore be recommended. Optimal spatial and contrast resolution is obtained at 80-90 keV. However, some reduction in perception of the finest structural details must be accepted.