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R Schnabel

Publications and source records attributed to R Schnabel.

At least 37 records · Page 2Linked to original sources
PubMed2001

Spontaneous breathing during partial liquid ventilation in animals with meconium aspiration.

Partial liquid ventilation (PLV) has been shown to improve gas exchange in paralyzed animals and humans with lung disease. The present study tests the hypothesis that PLV improves gas exchange in spontaneously breathing animals with meconium aspiration supported by proportional assist ventilation. Twenty-five adult anesthetized intubated rabbits with experimental meconium aspiration were randomized to gas ventilation (GV) or PLV while being supported by proportional assist ventilation. Minute ventilation, tidal volume, respiratory rate, mean airway pressure, heart rate, and mean arterial and pulmonary arterial pressure were recorded continuously. Every 30 min, arterial blood gases were obtained, and lung compliance, airway resistance, work of breathing, and cardiac output were measured. Animals were sacrificed after 5 h to obtain lung histology. More PLV animals survived until the end of the study period. PaO(2) (14.5 +/- 4.5 versus 25.6 +/- 6.7 kPa; p < 0.01; GV versus PLV) and lung compliance (4.3 +/- 0.4 versus 6.1 +/- 1.2 mL.kPa(-1).kg(-1); p < 0.001) were improved during PLV, resulting in a lower work of breathing (5.3 +/- 2.8 versus 3.5 +/- 1.5 mL.kPa.kg(-1); p < 0.05) and less need for ventilatory support. Minute ventilation and respiratory rate were higher during GV versus PLV, resulting in a slightly lower PaCO(2) (3.9 +/- 0.5 versus 4.5 +/- 0.7 kPa; p < 0.05). Histologic evaluation showed more atelectasis, inflammatory changes, and hemorrhage in GV animals. Other parameters measured were similar. We conclude that PLV improves oxygenation, lung compliance, and survival and results in less lung injury in spontaneously breathing animals with meconium aspiration when supported by proportional assist ventilation.

Animals↗
PubMed2000

CYK-4: A Rho family gtpase activating protein (GAP) required for central spindle formation and cytokinesis.

During cytokinesis of animal cells, the mitotic spindle plays at least two roles. Initially, the spindle positions the contractile ring. Subsequently, the central spindle, which is composed of microtubule bundles that form during anaphase, promotes a late step in cytokinesis. How the central spindle assembles and functions in cytokinesis is poorly understood. The cyk-4 gene has been identified by genetic analysis in Caenorhabditis elegans. Embryos from cyk-4(t1689ts) mutant hermaphrodites initiate, but fail to complete, cytokinesis. These embryos also fail to assemble the central spindle. We show that the cyk-4 gene encodes a GTPase activating protein (GAP) for Rho family GTPases. CYK-4 activates GTP hydrolysis by RhoA, Rac1, and Cdc42 in vitro. RNA-mediated interference of RhoA, Rac1, and Cdc42 indicates that only RhoA is essential for cytokinesis and, thus, RhoA is the likely target of CYK-4 GAP activity for cytokinesis. CYK-4 and a CYK-4:GFP fusion protein localize to the central spindle and persist at cell division remnants. CYK-4 localization is dependent on the kinesin-like protein ZEN-4/CeMKLP1 and vice versa. These data suggest that CYK-4 and ZEN-4/CeMKLP1 cooperate in central spindle assembly. Central spindle localization of CYK-4 could accelerate GTP hydrolysis by RhoA, thereby allowing contractile ring disassembly and completion of cytokinesis.

Animals↗
PubMed2000

Is geomagnetic activity a risk factor for sudden unexplained death in epilepsies?

OBJECTIVE: To test the hypothesis that sudden unexplained death (SUD) in epilepsy is related to geomagnetic activity. BACKGROUND: Prior studies presume that geomagnetic activity (with average amplitudes above 50 nanotesla [nT]) is associated with SUD in epileptic human patients and in epileptic laboratory rats. METHODS: In a retrospective study, 46 epileptic patients with definite SUD were compared with 108 epileptic patients with known cause of death (KCD) who died between 1981 and 1992. A complete postmortem examination was performed in all cases. The time of the day and date of death, as well as two international geomagnetic indices concerning Bartels' planetary 3-hour signs (Kp) and the mean planetary daily amplitudes (Ap) at time of death, were assessed. RESULTS: Among 45 SUD individuals, the local time (37.8%) and the universal time of death (35.6%) peaked within the critical period between 3 to 9 AM. However, the SUD and KCD group did not substantially differ in regard to the distribution of local or universal time of death (p > 0.2, Fisher test). Neither the Kp signs at death and 2 hours before death nor the Ap values showed considerable differences between the SUD and KCD series (p > 0.2, Mann-Whitney test). Merely 4.3% of SUD patients and 3.7% of KCD patients were associated with Ap indices above 50 nT (p > 0.2, Fisher test). CONCLUSION: The results do not support the hypothesis that geomagnetic activity is related to occurrence of sudden unexplained death in epileptic patients.

Adult↗
PubMed2000

Parental deprivation induces N-methyl-D-aspartate-receptor upregulation in limbic brain areas of Octodon degus: protective role of the maternal call.

An optimal coordination between parents and their offspring involves a sequence of reciprocal behaviors to ensure the adequate care of the young, which is critical for a healthy physical, emotional, and social development. Parental deprivation, particularly an impaired child-mother attachment, induces lasting changes in emotional as well as in cognitive capacities in later life. We assessed in the South American precocial species, Octodon degus, whether alterations of glutamatergic function of the limbic system induced by parental deprivation may be a neural correlate for such behavioral changes. Further, we analyzed whether the mother's voice can protect from separation-induced changes of brain function. Changes of N-methyl-D-aspartate (NMDA) receptor expression were examined in the following three groups of 2-week-old Octodon degus pups: (I) control animals who remained undisturbed with the family; (II) animals who were repeatedly separated from the family and individually placed in an unfamiliar environment for behavioral analysis (open field); and (III) animals who were treated like the group described under (II) but were presented with maternal vocalizations during separation. Relative to those in the control group I, the animals in group II showed an upregulation of NMDA receptor density in the (a) anterior cingulate, prelimbic, infralimbic, and anterior insular cortices; (b) CA1/stratum radiatum; (c) CA1/stratum lacunosum moleculare and CA3/stratum radiatum; and (d) in the basomedial amygdaloid nucleus. Presentation of the maternal call during the separation period (group III) suppressed the separation-induced NMDA receptor upregulation in all regions. The results demonstrate that early life events can influence the expression of transmitter receptors and that maternal behavior, acting to control the pup's socio-emotional environment, is a key factor for regulating such developmental events.

Animals↗
PubMed2000

OOC-3, a novel putative transmembrane protein required for establishment of cortical domains and spindle orientation in the P(1) blastomere of C. elegans embryos.

Asymmetric cell divisions require the establishment of an axis of polarity, which is subsequently communicated to downstream events. During the asymmetric cell division of the P(1) blastomere in C. elegans, establishment of polarity depends on the establishment of anterior and posterior cortical domains, defined by the localization of the PAR proteins, followed by the orientation of the mitotic spindle along the previously established axis of polarity. To identify genes required for these events, we have screened a collection of maternal-effect lethal mutations on chromosome II of C. elegans. We have identified a mutation in one gene, ooc-3, with mis-oriented division axes at the two-cell stage. Here we describe the phenotypic and molecular characterization of ooc-3. ooc-3 is required for the correct localization of PAR-2 and PAR-3 cortical domains after the first cell division. OOC-3 is a novel putative transmembrane protein, which localizes to a reticular membrane compartment, probably the endoplasmic reticulum, that spans the whole cytoplasm and is enriched on the nuclear envelope and cell-cell boundaries. Our results show that ooc-3 is required to form the cortical domains essential for polarity after cell division.

Amino Acid Sequence↗
PubMed1999

Ballistic transformation of Caenorhabditis elegans.

A novel method to transform the nematode Caenorhabditis elegans is described. DNA coprecipitated with gold particles is shot at worms by means of a helium beam. Transformed worms are either identified by a dominant visible marker or selected by a conditional lethal system.

Animals↗
PubMed1999

Dissection of cell division processes in the one cell stage Caenorhabditis elegans embryo by mutational analysis.

To identify novel components required for cell division processes in complex eukaryotes, we have undertaken an extensive mutational analysis in the one cell stage Caenorhabditis elegans embryo. The large size and optical properties of this cell permit observation of cell division processes with great detail in live specimens by simple differential interference contrast (DIC) microscopy. We have screened an extensive collection of maternal-effect embryonic lethal mutations on chromosome III with time-lapse DIC video microscopy. Using this assay, we have identified 48 mutations in 34 loci which are required for specific cell division processes in the one cell stage embryo. We show that mutations fall into distinct phenotypic classes which correspond, among others, to the processes of pronuclear migration, rotation of centrosomes and associated pronuclei, spindle assembly, chromosome segregation, anaphase spindle positioning, and cytokinesis. We have further analyzed pronuclear migration mutants by indirect immunofluorescence microscopy using antibodies against tubulin and ZYG-9, a centrosomal marker. This analysis revealed that two pronuclear migration loci are required for generating normal microtubule arrays and four for centrosome separation. All 34 loci have been mapped by deficiencies to distinct regions of chromosome III, thus paving the way for their rapid molecular characterization. Our work contributes to establishing the one cell stage C. elegans embryo as a powerful metazoan model system for dissecting cell division processes.

Animals↗
PubMed1999

The dorsocaudal neostriatum of the domestic chick: a structure serving higher associative functions.

The dorsocaudal neostriatal (dNC) complex consists of at least three functionally distinct subregions and is part of an 'imprinting' pathway, which interconnects several forebrain regions that are known to be involved in juvenile learning. Based on its anatomical features, at least one subregion of the dNC complex, the neostriatum dorsocaudale (Ndc) may be considered as the equivalent of the mammalian polysensory association cortices. Several lines of evidence point to a role for this forebrain region in learning and memory formation. After auditory or visual imprinting changes of stimulus-evoked metabolic activities and of synaptic densities have been measured in the Ndc. Pharmacological behavioral studies revealed that the activation of NMDA receptors plays a critical role during this learning process and that NMDA receptor activation is required for the associated metabolic and synaptic changes. In addition to glutamatergic afferents, anatomical studies revealed a massive input from monoaminergic and peptidergic pathways into the dNC complex, suggesting a modulatory role for these systems during imprinting. The results presented here together with data from other avian species support the view that the dNc complex, and in particular the Ndc, plays an important role in juvenile and adult learning.

Animals↗
PubMed1999

[Amalgam deposit in a gastric leiomyosarcoma. Case report of an unusual amalgam constellation].

We report an a 57-year-old man with gastric leiomyosarcoma containing depositions of amalgam that possibly originate from a swallowed filling. The significance of this finding remains unclear. This case does not permit any conclusions as to whether this is a coincidence or not. The worldwide use of amalgam without an increase of oral sarcomas/leiomyosarcomas speaks against the supposition that amalgam induces sarcomas.

Dental Amalgam↗
PubMed1999

Reverse relationship between beta-amyloid precursor protein and beta-amyloid peptide plaques in Down's syndrome versus sporadic/familial Alzheimer's disease.

Strong genetic evidence has been accumulated in favor of a central role of beta-amyloid precursor protein (APP) and beta-amyloid peptide (betaA4) in the pathogenesis of Alzheimer's disease (AD). We employed four newly developed APP and betaA4 antibodies and performed a comparative neuropathological study of patients with Down's syndrome (DS), early-onset familial AD and sporadic AD to investigate the distribution of APP and betaA4 plaque densities in the cerebral cortex of these disorders. Quantitative analysis of APP versus betaA4 plaques revealed that brains with early-onset familial AD and sporadic AD showed significantly more betaA4 plaques than brains with DS (P < 0.05). In contrast, APP plaques were more abundant in DS cerebral cortex (P < 0.02). These observations suggest that the development of pathological changes in DS brains does not parallel that observed in AD, which might be attributable to different causes in the pathogenesis of betaA4 formation. A comparison of these disorders may be useful to further complement our knowledge of the mechanisms leading to plaque development.

3T3 Cells↗
PubMed1999

A CaMKII inhibitor, KN-62, facilitates DHPG-induced LTD in the CA1 region of the hippocampus.

We have shown previously that activation of mGlu receptors using a group I specific mGlu receptor agonist, (R,S)-3,5-dihydroxyphenylglycine (DHPG), can induce long-term depression (LTD) in the CA1 region of the hippocampus (Palmer et al., 1997). We now report that DHPG-induced LTD is facilitated by treatment with KN-62, an inhibitor of certain Ca2+/calmodulin-dependent protein kinases (CaMKs), including CaMKII.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1999

An investigation into signal transduction mechanisms involved in DHPG-induced LTD in the CA1 region of the hippocampus.

Previously, we have found that activation of mGlu receptors using a group I-specific mGlu receptor agonist, (RS)-3,5-DHPG, can induce long-term depression (LTD) in the CA1 region of the hippocampus and that, once established, this synaptic depression can be reversed by application of the mGlu receptor antagonist, (S)-MCPG [Palmer et al., 1997. Neuropharmacology 36, 1517-1532]. We have started to investigate the signal transduction mechanisms involved in these effects. Group I mGlu receptors couple to phospholipase C and therefore can activate protein kinase C and mobilise Ca2+ from intracellular stores. However, neither protein kinase C inhibitors (chelerythrine or Ro 31-8220) nor agents which deplete intracellular Ca2+ stores (thapsigargin or cyclopiazonic acid) were able to prevent DHPG-induced LTD. Furthermore, the ability of MCPG to reverse DHPG-induced LTD was not prevented by these compounds. These results suggest that it is unlikely that DHPG-induced LTD, or its reversal by MCPG, is produced via activation of either protein kinase C or by release of Ca2+ from intracellular stores.

Alkaloids↗
PubMed1999

Comparison between premortem and postmortem serum concentrations of phenobarbital, phenytoin, carbamazepine and its 10,11-epoxide metabolite in institutionalized patients with epilepsy.

The last premortem serum concentrations of phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ) and its CBZ-10,11-epoxide metabolite (CE) were compared with the corresponding postmortem serum concentrations in 16 adult patients of an epilepsy centre. Based on complete postmortem examinations, 12 individuals showed a known cause of death (KCD) and four patients succumbed from sudden unexplained death (SUD). The last premortem and the postmortem serum levels of PB (r = 0.991), PHT (r = 0.986), CBZ (r = 0.985) and CE (r = 0.936) were highly correlated. However, the regression analysis indicated that, except for CE, the premortem concentrations were significantly higher than the postmortem concentrations, i.e. 65% for PB, 34% for PHT, and 16% for CBZ. Varying time lapses (4-62 h) between death and serum sampling during autopsy did not significantly influence the ratio of premortem to postmortem serum levels for PB, PHT, CBZ, and CE (p > 0.1). Furthermore we found no significant differences between the premortem and the postmortem serum concentration ratios CE/CBZ. Considering the above variables, the data of SUD and KCD patients were comparable. Postmortem decrease in anticonvulsant serum concentrations, especially for PB and PHT, should be considered in order to avoid misinterpretation in respect to so-called 'subtherapeutic' serum levels and noncompliance in context with SUD or fatal intoxication.

Adult↗
PubMed1999

High-frequency oscillatory ventilation is not superior to conventional mechanical ventilation in surfactant-treated rabbits with lung injury.

The aim of this study was to compare high-frequency oscillatory ventilation (HFOV) with conventional mechanical ventilation (CMV) with and without surfactant in the treatment of surfactant-deficient rabbits. A previously described saline lung lavage model of lung injury in adult rabbits was used. The efficacy of each therapy was assessed by evaluating gas exchange, lung deflation stability and lung histopathology. Arterial oxygenation did not improve in the CMV group without surfactant but increased rapidly to prelavage values in the other three study groups. During deflation stability, arterial oxygenation decreased to postlavage values in the group that received HFOV alone, but not in both surfactant-treated groups (HFOV and CMV). The HFOV group without surfactant showed more cellular infiltration and epithelial damage compared with both surfactant-treated groups. There was no difference in gas exchange, lung deflation stability and lung injury between HFOV and CMV after surfactant therapy. It is concluded that the use of surfactant therapy in combination with high-frequency oscillatory ventilation is not superior to conventional mechanical ventilation in improving gas exchange, lung deflation stability and in the prevention of lung injury, if lungs are kept expanded. This indicates that achieving and maintaining alveolar expansion (i.e. open lung) is of more importance than the type of ventilator.

Administration, Topical↗
PubMed1999

Isolation, characterization and immunolocalization of phosphorylcholine-substituted glycolipids in developmental stages of Caenorhabditis elegans.

Caenorhabditis elegans displays three neutral glycosphingolipids with structural homology to glycosphingolipids from the porcine nematode parasite, Ascaris suum. The present findings extend the degree of structural conservation between the two nematode species to glycosphingolipids with a phosphodiester substitution. Using a combination of hydrofluoric acid pretreatment, immunochemical characterization and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, three zwitterionic, phosphorylcholine-substituted glycosphingolipids could be identified in the neutral glycolipid fraction of C. elegans. The components were isolated as their zwitterionic, phosphorylcholine-substituted, pyridylaminated oligosaccharides by HPLC. Structural analysis was performed using hydrofluoric acid treatment, partial acid hydrolysis, methylation analysis, gas chromatography-mass spectrometry, cleavage with exoglycosidases and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Their chemical structures are proposed as: component Nz1, GalNAc(beta1-4)[phosphorylcholine]GlcNAc(beta1-3)Man(beta1-4)Glc-cera mide; component Nz2, Gal(alpha1-3)GalNAc(beta1-4)[phosphorylcholine]-GlcNAc(beta1-3)Man(be ta1-4)Glc-ceramide; and component Nz3, Gal(beta1-3)- Gal(alpha1-3)GalNAc(beta1-4)[phosphorylcholine]GlcNAc(beta1-3)Man(bet a1-4)Glc-ceramide. The oligosaccharide core is characteristic of the biosynthetic arthro-carbohydrate series of protostomial glycosphingolipids. The ceramide moiety was specified by a d17 : 1 sphingoid-base with iso-branching and anteiso-branching, and 2-hydroxy, saturated fatty acids as represented by docosanoic and tetracosanoic acids. Analysis of the spatial and temporal expression of the phosphorylcholine epitope, during embryonic and postembryonic development, showed it to be localized predominantly in seam cells and basement membranes, respectively. In early embryonic ontogenesis the phosphorylcholine epitope was only lipid bound, while in late embryonic and postembryonic development this epitope was both lipid bound and protein bound.

Animals↗
PubMed1999

Effect of social experience on dopamine-stimulated adenylyl cyclase activity and G protein composition in chick forebrain.

The stimulation of adenylyl cyclase (AC) by dopamine was investigated in membrane fractions of the forebrain areas mediorostral neostriatum/hyperstriatum ventrale (MNH) and lobus parolfactorius (LPO) of 8-day-old domestic chicks that had been raised under different social conditions: group A, socially isolated; group B, imprinted on an acoustic stimulus; group C, trained but nonimprinted; and group D, reared in small groups. Only in the brain of the socially experienced groups could cyclic AMP (cAMP) synthesis be stimulated by dopamine, but not in the socially isolated animals (group A). Ligand binding studies of dopamine D1- and D2-type receptors in membrane fractions did not reveal differences between socially experienced and isolated animals. Forskolin stimulation of total AC in MNH and LPO membrane fractions revealed a significantly enhanced AC stimulation in the socially reared but not in the imprinted group compared with isolated controls. Stimulation of AC by the G protein activator guanylylimidodiphosphate was significantly increased in the MNH and the LPO of socially reared chicks compared with isolated control animals. These results suggest that early postnatal social experience modulates the rate of cAMP synthesis and that these lasting changes are not due to changes of dopamine receptors but are related to increased AC activities and to increased sensitivity of Gs protein.

Adenylyl Cyclases↗
PubMed1999

Comparison of exogenous surfactant therapy, mechanical ventilation with high end-expiratory pressure and partial liquid ventilation in a model of acute lung injury.

We have compared three treatment strategies, that aim to prevent repetitive alveolar collapse, for their effect on gas exchange, lung mechanics, lung injury, protein transfer into the alveoli and surfactant system, in a model of acute lung injury. In adult rats, the lungs were ventilated mechanically with 100% oxygen and a PEEP of 6 cm H2O, and acute lung injury was induced by repeated lung lavage to obtain a PaO2 value < 13 kPa. Animals were then allocated randomly (n = 12 in each group) to receive exogenous surfactant therapy, ventilation with high PEEP (18 cm H2O), partial liquid ventilation or ventilation with low PEEP (8 cm H2O) (ventilated controls). Blood-gas values were measured hourly. At the end of the 4-h study, in six animals per group, pressure-volume curves were constructed and bronchoalveolar lavage (BAL) was performed, whereas in the remaining animals lung injury was assessed. In the ventilated control group, arterial oxygenation did not improve and protein concentration of BAL and conversion of active to non-active surfactant components increased significantly. In the three treatment groups, PaO2 increased rapidly to > 50 kPa and remained stable over the next 4 h. The protein concentration of BAL fluid increased significantly only in the partial liquid ventilation group. Conversion of active to non-active surfactant components increased significantly in the partial liquid ventilation group and in the group ventilated with high PEEP. In the surfactant group and partial liquid ventilation groups, less lung injury was found compared with the ventilated control group and the group ventilated with high PEEP. We conclude that although all three strategies improved PaO2 to > 50 kPa, the impact on protein transfer into the alveoli, surfactant system and lung injury differed markedly.

Animals↗