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D Neumann

Publications and source records attributed to D Neumann.

At least 37 records · Page 2Linked to original sources
PubMed1998

Withdrawal of 2-mercaptoethanol induces apoptosis in a B-cell line via Fas upregulation.

Mouse lymphoid cell cultures are dependent on reducing agents in their culture medium to allow proliferation and survival of the cells. In the case of the mouse CD5+-pre-B cell line SPGM-1, withdrawal of 2-mercaptoethanol (2-ME) resulted in rapid inhibition of proliferation and subsequent cell death by apoptosis. The pathways leading to cell death by withdrawal of 2-ME or by incubation with ionomycin, a known inducer of apoptosis, were compared. Both kinds of stimulation resulted in apoptosis of the whole population, but cell death occurred with different kinetics. Only apoptosis induced by ionomycin was inhibited by coincubation with the phorbol ester PMA, while apoptosis induced by withdrawal of 2-ME was not. Overexpression of the human bcl-2 proto-oncogene in these cells delayed the death process induced by either method. SPGM-1xbcl-2 cells accumulated in the G0/G1 and G2/M cell cycle phases after removal of 2-ME from the medium, whereas treatment with ionomycin resulted in an arrest only in the G0/G1 transition. Interestingly, both stimuli induced the expression of the Fas receptor, but with different kinetics, while the Fas ligand (FasL) was expressed constitutively in SPGM-1 cells. These data demonstrate that withdrawal of 2-ME and incubation with ionomycin both induce rapid cell death by apoptosis, possibly mediated by an autocrine Fas/FasL loop. Although the initial pathways activated by the two forms of treatment must be different, they converge on a common level controlled by the anti-apoptotic gene product Bcl-2.

Animals↗
PubMed1998

[Clearance of liposome-incorporated ciprofloxacin after intravitreal injection in rabbit eyes].

BACKGROUND: Ciprofloxacin (CIP) is a fluoroquinolone-antibiotic with a high antimicrobial activity against all pathogens causing bacterial endophthalmitis. After intravitreal injection, however, elimination half-life of this antibiotic is only 2.2 hours. To prolong intraocular bioavailability this study was performed to incorporate CIP into liposomes and to determine its clearance from the vitreous after intravitreal injection. MATERIALS AND METHODS: CIP was incorporated into multilamellar vesicles by mechanical dispersion. 0.1 ml of this suspension (equiv. 273.6 micrograms CIP) was injected into the midvitreous of pigmented rabbit eyes (Chinchilla-bastards). One day, 3 and 14 days after the injection intravitreal concentration of CIP was determined by means of high-pressure-liquid-chromatography after dissolution of the liposomes by ultrasound. At the same intervals serum concentration of the antibiotic was examined as well. RESULTS: Within 24 hours intravitreal concentration fell to 18.0 micrograms/ml. Three days after the injection the concentration of CIP was 6.9 micrograms/ml. This is still above the minimal inhibitory concentration (MIC90) of the most common ocular pathogens. At 14 days CIP was not detectable in the vitreous any more. The serum concentration was between 0.04 microgram/ml and 0.07 microgram/ml. 3 and 14 days after injection no CIP could be detected. CONCLUSIONS: This study shows that the incorporation of CIP into liposomes can be achieved in sufficient doses by mechanical dispersion method. After intravitreal application the bioavailability of the antibiotic can be markedly improved. Even after 3 days the intravitreal levels were above the MIC90 of the most common endophthalmitis pathogens.

Animals↗
PubMed1998

The paralimbal approach with deferred conjunctival closure for adjustable strabismus surgery.

Interest in the adjustable suture technique was renewed in the mid-1970s. The authors report a new modification of the fornix and limbal conjunctival approaches that combines the advantages of both. A paralimbal conjunctival incision is placed halfway between the limbus and the muscle insertion and directed parallel to the muscle insertion. This approach permits easy access to the rectus muscle. After the adjustable suture is temporarily secured with a bow-tie knot, the conjunctiva is partially closed using a loop suture over the muscle suture. An optional modification is the use of a "sweep suture" to break early adhesions at the time of adjustment. The adjustment procedure is performed at least 6 hours after the surgery. The conjunctiva is retracted as necessary for access to the muscle suture. If a sweep suture is used, this is first withdrawn before attempting any adjustment. After adjustment, the conjunctival loop suture is closed, covering the muscle suture. The sweep suture serves as a safeguard for what may otherwise be a difficult adjustment. This approach increases patient comfort after the surgery.

Conjunctiva↗
PubMed1997

Phosphorylation of erythropoietin receptors in the endoplasmic reticulum by pervanadate-mediated inhibition of tyrosine phosphatases.

Erythropoietin (EPO) is the major hormone regulating the proliferation of erythroid precursors and their differentiation into erythrocytes. Ligand binding to the erythropoietin receptor (EPO-R), a member of the cytokine receptor family, triggers Tyr phosphorylation of the surface form of the receptor, presumably mediated by the Janus kinase (JAK) 2. To study whether non-surface EPO-R can be phosphorylated, Ba/F3 cells stably transfected with EPO-R were treated with pervanadate (PV), which is widely used as a potent tool to inhibit cellular protein Tyr phosphatases, thus resulting in enhanced Tyr phosphorylation of cellular proteins. PV treatment caused the EPO-R to undergo Tyr phosphorylation in a time-dependent and dose-dependent manner. PV-mediated Tyr phosphorylation of EPO-R occurred at several intracellular sites including the endoplasmic reticulum (ER), because both endoglycosidase H (endo H)-resistant EPO-R and the ER-retained EPO-R mutant (DeltaWS1 EPO-R) were Tyr phosphorylated in response to PV. Moreover, in metabolic labelling experiments, endo H-sensitive EPO-R was also phosphorylated. The phosphorylated fraction accounted for only 30-50% of the newly synthesized EPO-R, the fraction that normally exits from the ER. Tyr phosphorylation could not be detected on proteolytic fragments of the EPO-R, suggesting that this is a highly regulated process. Unlike the wild-type (wt) EPO-R, which was phosphorylated both on EPO binding and after inhibition of Tyr phosphatases by PV treatment, an EPO-R mutant (W282R EPO-R) that does not activate JAK2 was phosphorylated after PV treatment but not by EPO binding. Both EPO-R and JAK2 were phosphorylated with similar kinetics by PV treatment, suggesting that JAK2, as well as protein Tyr kinases different from JAK2, might mediate PV-dependent EPO-R phosphorylation. Furthermore the Tyr-phosphorylated ER-retained EPO-R mutant DeltaWS1 co-immunoprecipitated with JAK2 kinase, indicating that the EPO-R might interact with JAK2 while in the ER.

Animals↗
PubMed1997

Ultrasonographically guided injection of corticosteroids for the treatment of retroseptal capillary hemangiomas in infants.

PURPOSE: Injection of corticosteroids is a well-documented and successful mode of treatment for periorbital capillary hemangiomas. Because of the greater potential risk involved with retrobulbar injections, no prior study has described this treatment for tumors located behind the orbital septum. Although retroseptal intraorbital capillary hemangiomas comprise only 7% of all adnexal capillary hemangiomas, complications such as optic nerve compression or astigmatism may necessitate treatment. METHODS: Three patients with deep orbital hemangiomas that caused vision-threatening complications were treated with intralesional injections of triamcinolone and betamethasone. Orbital injection was performed with use of real-time ultrasonographic guidance of the needle. This technique was valuable in providing continuous, accurate, and safe advancement of the needletip in the orbit to avoid the globe and orbital walls. Ultrasonography also permitted precise placement of the needle tip within the tumor and visualization of the injected material. RESULTS: Significant improvement was demonstrated in all cases on the basis of both ultrasonographic measurements and regression of clinical manifestations such as astigmatism, chemosis, proptosis, and optic nerve pallor. No complications were noted. CONCLUSION: Intralesional injection of corticosteroids to treat retroseptal and retrobulbar capillary hemangiomas was found to be a safe and effective treatment modality in our patients. Positioning of the injecting needle was guided by ultrasonography.

Adrenal Cortex Hormones↗
PubMed1997

Kinematic and neuromuscular changes of the gait pattern after Achilles tendon rupture.

After long immobilization periods in equinovalgus with operated Achilles tendon rupture, long-lasting changes of motor patterns in functional movement can be expected. In the present study, possible alterations in gait pattern have been analyzed based on kinematic and neuromuscular parameters. Ten patients 1 year after surgery and a healthy control group performed 10 gait cycles in natural walking cadence. Ankle motion, pressure distribution, and electromyographic data were recorded and analyzed in defined phases. Kinematic and neuromuscular changes are still evident 1 year after surgery with a temporal phase shift and a neuromuscular deficit of the lateral gastrocnemius muscle. The objective of rehabilitation should be the facilitation of the temporal innervation pattern of the lateral gastrocnemius muscle in the functional movement.

Achilles Tendon↗
PubMed1997

Analytical electron microscopy as a powerful tool in plant cell biology: examples using electron energy loss spectroscopy and X-ray microanalysis.

Energy filtering transmission electron microscopy in combination with energy dispersive X-ray analysis (EDX) and quantumchemical calculations opens new possibilities for elemental and bone analysis at the ultrastructural level. The possibilities and limitations of these methods, applied to botanical samples, are discussed and some examples are given. Ca-oxalate crystals in plant cell vacuoles show a specific C K-edge in the electron energy loss spectrum (EELS), which allows a more reliable identification than light microscopical or cytochemical methods. In some dicots crystalline inclusions can be observed in different cell compartments, which are identified as silicon dioxide or calcium silicate by the fine structure of the Si L2,3-edge. Their formation is discussed on the basis of EEL-spectra and quantumchemical calculations. Examples concerning heavy metal detoxification are given for some tolerant plants. In Minuartia Zn is bound as Zn-silicate in cell walls; Armeria accumulates Cu in leaf idioblasts by chelation with phenolic compounds and Cd is precipitated as CdS/phytochelatin-complexes in tomato.

Calcium Compounds↗
PubMed1997

Interaction between interleukin-1 and ciliary neurotrophic factor in the regulation of neuroblastoma cell functions.

Human neuroblastoma cells SK-N-SH express significant numbers of IL-1R type I on their surface, as detected by saturation binding and RT-PCR, and are responsive to IL-1beta activation by producing inflammatory cytokines IL-6 and IL-8. IL-1beta can also have an indirect effect on nervous cell functions, since it is able to modulate the stimulus-induced increase of intracellular Ca++ levels, one of the first steps of the cell activation mechanism. In fact, on SK-N-SH neuroblastoma cells, IL-1beta can inhibit the Ca++ increase induced by stimulation of acetylcholine receptors with carbachol. In parallel to IL-1beta, the neurotrophic factor CNTF also shows an inhibitory effect on carbachol-stimulated Ca++ increase in CNTFRalpha-expressing SK-N-SH cells. However, when simultaneously present, the two cytokines cross-inhibit, thus allowing full cell activation in response to the cholinoceptor agonist. The inhibitory effect of CNTF on IL-1beta activities on nervous cells was confirmed in the IL-6 production assay. In fact, while CNTF could not induce IL-6 production, it could strongly inhibit cytokine production in response to IL-1beta in SK-N-SH cells. The down-modulation of IL-1 effects by CNTF could be one of the mechanisms controlling the extent of the inflammatory reaction at the nervous system level.

Ciliary Neurotrophic Factor↗
PubMed1996

A plastid enzyme arrested in the step of precursor translocation in vivo.

The key enzyme of chlorophyll biosynthesis in higher plants, NADPH:protochlorophyllide (Pchlide) oxidoreductase (POR, EC 1.3.1.33), accumulates in its precursor form (pPORA) in barley. pPORA is bound to the chloroplasts and is able to interact with the enzyme's substrate, Pchlide, at both the cytosolic as well as the stromal side of the plastid envelope. The interaction with intraplastidic Pchlide, formed in ATP-containing chloroplasts upon feeding with -aminolevulinic acid, drives vectorial translocation of pPORA across the plastid envelope membranes. In contrast, exogenously applied Pchlide causes the release of the envelope-bound precursor protein to the cytosol. Both processes compete with each other if intra- and extraplastidic Pchlide are applied simultaneously. A cytosolic heat shock cognate protein of Mr 70,000 present in wheat germ and barley leaf protein extracts appears to prevent the release of the pPORA to the cytosol in vivo, however.

Journal Article↗
PubMed1996

Co-expression of mRNA for type I and type II interleukin-1 receptors and the IL-1 receptor accessory protein correlates to IL-1 responsiveness.

Three cell surface molecules participate in Interleukin-1 (IL-1) binding and signal generation, the two distinct types of receptors (type I IL-1R and type II IL-1R) and the IL-1 receptor accessory protein (IL-1RAcP). Low surface expression hampers the detection of all three components on a protein level in most cell types, thus the highly sensitive RT-PCR was used to analyse the mRNA expression in a panel of 18 murine cell types of different hemopoietic lineages and fibroblasts. The transcription of both types of IL-1 receptors was detected in all cell lines tested. In most cell lines the IL-1RAcP was co-expressed with the IL-1 receptors, and only these lines responded to IL-1. However, in three cell lines no mRNA for the IL-1RAcP could be detected, and these cells did not respond to IL-1. These results suggest that the expression of the IL-1RAcP correlates with IL-1 responsiveness and they point to a pivotal role for the IL-1RAcP in IL-1 signal generation.

Animals↗
PubMed1996

Blocking intracellular degradation of the erythropoietin and asialoglycoprotein receptors by calpain inhibitors does not result in the same increase in the levels of their membrane and secreted forms.

The erythropoietin receptor (EPO-R), a type 1 membrane glycoprotein, is degraded mainly in the lysosomes or endosomes, whereas the asialoglycoprotein receptor (ASGP-R) H2a subunit, a type 2 membrane glycoprotein, is degraded exclusively in the endoplasmic reticulum. The present study describes compounds that inhibit the intracellular degradation of these receptors in an efficient manner. However, the levels of cell-surface expression and secretion of their soluble exoplasmic domains were not enhanced to the same extent. The calpain inhibitors N-acetyl-leucyl-leucyl-norleucinal (ALLN) and N-acetyl-leucyl-leucyl-methional (ALLM) inhibited EPO-R degradation profoundly. After 3 h of chase using Ba/F3 cells and NIH 3T3 fibroblasts expressing the EPO-R, virtually all of the receptor molecules were degraded, whereas 80% of the pulse-labelled receptor remained intact in the presence of the inhibitor. EPO-R cell-surface expression was elevated 1.5-fold after 1 h of incubation with ALLN. In the absence of protein synthesis, ALLN caused the accumulation of non-degraded EPO-R molecules in endosomes and lysosomes, as determined by double immunofluorescence labelling of NIH 3T3 cells expressing EPO-Rs. In Ba/F3 cells expressing a soluble EPO-R, ALLN treatment increased secretion of the soluble exoplasmic domain of the EPO-R 2-5-fold. Similarly, in NIH 3T3 cells singly transfected with the ASGP-R H2a subunit cDNA, ALLN inhibited degradation of the ASGP-R H2a subunit precursor, as well as the degradation of the 35 kDa proteolytic fragment corresponding to the receptor ectodomain, by 3-6-fold. However, accumulation of secreted proteolytic fragment in the medium was augmented in the presence of ALLN by only 1.75-fold. In cells expressing the G78R mutant of the ASGP-R H2a subunit, which is not cleaved to the 35 kDa fragment [Yuk and Lodish (1993) J. Cell Biol. 123, 1735-1749], degradation of the precursor was inhibited. Overall, our data suggest the involvement of cysteine proteinases located in the endoplasmic reticulum, as well as in post-Golgi compartments, in degradation of the EPO-R and the ASGP-R H2a subunit. The much lower effect of the inhibitory compounds on cell-surface and secreted forms of the EPO-R and ASGP-R H2a subunit illustrates the complexity and the tight regulation of the cellular localization and stability of membrane proteins.

3T3 Cells↗
PubMed1996

[Not Available].

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Austria↗
PubMed1996

Erythropoietin stimulates atrial natriuretic peptide secretion from adult rat cardiac atrium.

Hypoxia is a powerful stimulus for erythropoietin (EPO) secretion from the kidney and for atrial natriuretic peptide (ANP) secretion from atrial myocytes. EPO is involved in the long term defense mechanism against hypoxia via stimulation of erythropoiesis. ANP is involved in the short-term defense mechanism against hypoxia via improved pulmonary and heart functions. We investigated a possible interaction between these two hormones. We tested the hypothesis that EPO may stimulate ANP secretion from the cardiac atrium. This hypothesis was tested in two in vitro models; isolated rate atrium and cultured adult atria rat myocytes. Recombinant human EPO (5-10 units/ml) enhanced ANP secretion from the isolated atrium (by approximately 2-fold) within 10 min in a concentration-dependent manner. To define whether the action of EPO on ANP secretion is direct, we examined the effect of EPO on ANP release from adult rat cultured atrial myocytes. EPO failed to stimulate ANP secretion from cultured atrial myocytes, suggesting that EPO-induced ANP secretion is an indirect effect. Cyclooxygenase products (e.g.,prostaglandins) and endothelin 1 were shown to be potent secretagogues of ANP from cardiac atrium. To test whether EPO-induced ANP secretion from isolated perfused atrium is mediated by cyclooxygenase products and/or endothelin, we used inhibitors of the enzyme cyclooxygenase (indomethacin or aspirin) and the endothelin receptor ETA subtype antagonist BQ123. EPO-stimulated ANP secretion was not affected by indomethacin (10(-4) M) or aspirin (10(-4) M), whereas BQ123 (10(-6) M) completely abolished EPO-stimulated ANP secretion from cardiac atrium. Our results expand our knowledge on the interaction between EPO and ANP hormonal systems and the possible role in the acute defense mechanism against hypoxia.

Animals↗
PubMed1995

Lineage switch of a mouse pre-B cell line (SPGM-1) to macrophage-like cells after incubation with phorbol ester and calcium ionophore.

The mouse CD5 positive pre-B cell line SPGM-1 can be induced to switch its lineage commitment towards macrophage differentiation by treatment with a combination of phorbol ester and a calcium ionophore. When cultured with these reagents the pre-B cells ceased to proliferate and rapidly became adherent to plastic surfaces. This morphological change was accompanied by the loss of pre-B cell-specific surface markers, such as PB76 and most prominently the mu heavy chain of the immunoglobulin receptor complex. In addition, the mRNA of the surrogate light chain lambda 5 disappeared while the induction of lysozyme mRNA could be detected. Differentiated SPGM-1 cells phagocytosed latex beads and showed nonspecific esterase activity. The high efficiency and speed of differentiation in this cellular system makes SPGM-1 a highly suitable model for studying the phenomenon of lineage switching during hemopoesis.

Animals↗
PubMed1995

The effect of povidone-iodine solution applied at the conclusion of ophthalmic surgery.

PURPOSE: Povidone-iodine 5% solution decreases the incidence of postoperative endophthalmitis when used on the eye for preoperative preparation. We sought to determine whether it also minimized conjunctival bacterial flora immediately after surgery by preventing bacteria present on the surface of the eye from entering surgical wounds. METHODS: In 42 eyes of 40 patients, at the conclusion of surgery, on an alternating basis, each patient received either a drop of a broad-spectrum antibiotic solution (polymyxin B sulfate-neomycin sulfate-gramicidin) or a 5% povidone-iodine solution in the operated-on eye. Bacterial cultures were taken before and after surgery and 24 hours later. The 38 unoperated-on eyes in the unilateral cases served as control eyes. RESULTS: Relative to the control group, povidone-iodine was effective in preventing an increase in the number of colony-forming units (P = .035), while the antibiotic was not. At 24 hours after surgery, the species count was lower in the eyes receiving povidone-iodine than in the antibiotic-treated eyes (P = .034) and was increased in the antibiotic group since the completion of surgery (P = .013), but was lower in the povidone-iodine and antibiotic groups than in the control eyes for both groups (P < .01). CONCLUSIONS: Povidone-iodine 5% solution applied to the eye at the conclusion of surgery was more effective at minimizing the number of colony-forming units and species for the first postoperative day than was a broad-spectrum antibiotic. While not true for the antibiotic, the antimicrobial effect of povidone-iodine lasted for at least 24 hours after the completion of surgery.

Bacteria↗
PubMed1995

Growth of the internal and external eye in term and preterm infants.

BACKGROUND: Better knowledge of the growth patterns of the external and internal eyes of neonates would permit more accurate diagnosis of disorders that affect ocular size such as infantile glaucoma and microphthalmos. Such disorders preferentially may affect certain parts of the internal eye but not other parts. No previous study statistically has evaluated internal ocular growth in preterm newborns. METHODS: A-scan ultrasonography was applied directly to the corneas of 101 healthy preterm and term newborns to determine axial length, anterior chamber depth, lens thickness, and vitreous chamber depth. The growth of these structures was evaluated by correlation and regression analyses. RESULTS: At term, the mean measurements were axial length, 16.2 mm; anterior chamber depth, 2.0 mm; lens thickness, 3.8 mm; and vitreous chamber depth, 10.5 mm. Postconceptional age correlated to axial length (P < 0.001), anterior chamber depth (P = 0.032), and vitreous chamber depth (P < 0.001), but not to lens thickness (P = 0.48). By regression analysis, the eyes of males grew faster than those of females (P < 0.001) mainly due to the vitreous chamber. CONCLUSION: In the last trimester and first 2 postnatal months, lens thickness remains constant, while the anterior chamber and, especially, the vitreous chamber deepen.

Anterior Chamber↗