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E Gilbert

Publications and source records attributed to E Gilbert.

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

Regulation of CD95 (APO-1/Fas) receptor and ligand expression by lipopolysaccharide and dexamethasone in parenchymal and nonparenchymal rat liver cells.

The effect of lipopolysaccharide (LPS) on the expression of CD95 (APO-1/Fas) receptor and ligand (CD95L) was studied in primary cultures of rat liver Kupffer cells (KCs), sinusoidal endothelial cells (SECs), and parenchymal cells (PCs) at the messenger RNA (mRNA) level and by means of immunocytochemistry. LPS treatment of KCs and SECs led to a three- to five-fold increase in CD95L mRNA levels within 6 hours, which declined thereafter. Within 24 hours, the number of KCs and SECs staining positive for CD95L strongly increased. After a lag phase of 12 hours after LPS addition, in both cell types the mRNA levels for the soluble CD95 isoform increased approximately 10-fold; however, the number of KCs and SECs staining positive for transmembrane CD95 remained low and did not significantly increase. Compared with nonparenchymal cells, CD95L mRNA levels in primary hepatocyte cultures were low in the absence and presence of LPS. On the other hand, functionally active CD95 expression markedly increased in response to LPS in these cells. Dexamethasone diminished the LPS-induced stimulation of CD95L expression in nonparenchymal cells but markedly stimulated CD95L expression in PCs. Apoptosis of PCs and thymic lymphocytes was stimulated by the addition of supernatants derived from LPS-treated KC or SEC cultures and was apparently mediated by CD95L as assessed by its sensitivity to inhibitors of the CD95-dependent apoptotic pathway in PCs. The data suggest a complex and timely coordinated interplay between the various liver cell populations with respect to LPS-induced activation of the apoptotic machinery with potential relevance for immunoregulation.

Animals↗
PubMed1998

Pulmonary vascular resistance in dogs and minipigs--effects of hypoxia and inhaled nitric oxide.

The pig has been reported to present with a stronger hypoxic pulmonary vasoconstriction than many other species, including the dog, but it is not known whether this is associated with a different longitudinal partitioning of pulmonary vascular resistance (PVR). We investigated the relationships between cardiac output (Q) and mean pulmonary artery pressure (Ppa) minus occluded Ppa (Ppao), and effective pulmonary capillary pressure (Pc') minus Ppao, in seven minipigs and in seven dogs in hyperoxia (FI(O2) 0.4) and hypoxia (FI(O2) 0.1), first without, then with the inhalation of 80 ppm nitric oxide (NO) to inhibit any reversible component of PVR. Pc' was estimated from the Ppa decay curve following pulmonary artery balloon occlusion. In hyperoxia, minipigs compared to dogs had (Ppa - Ppao)/Q and (Pc' - Ppao)/Q plots shifted to higher pressures. Hypoxia at each level of Q increased Ppa - Ppao in minipigs more than in dogs, and Pc' - Ppao in minipigs only. Inhaled NO reversed hypoxia-induced changes in (Ppa - Ppao)/(Q and (Pc' - Ppao)/Q plots. We conclude that the minipig, compared to the dog, presents with higher PVR and reactivity including vessels downstream to the site of Pc' as determined by the arterial occlusion technique.

Administration, Inhalation↗
PubMed1997

In vivo effects of activated H-ras oncogene expressed in the liver and in urogenital tissues.

Transgenic mouse technology provides a direct genetic approach to in vivo carcinogenesis. In order to determine the oncogenic potential of an activated ras gene in liver, kidney and intestine, we created transgenic mice expressing the human H-ras oncogene under control of the L-type pyruvate-kinase gene. This gene is expressed in hepatocytes, enterocytes, proximal tubular cells of the kidney and endocrine pancreatic cells. Depending on lines, we observed hepatocarcinoma, polycystic kidney disease and an unexpected epididymis hyperplasia. These transgenic mice are an interesting model of polycystic kidney disease, and complete our study of the tissue-specificity of oncogene action.

Animals↗
PubMed1997

Bispecific monoclonal antibody complexes bound to primate erythrocyte complement receptor 1 facilitate virus clearance in a monkey model.

We investigated the feasibility of using bispecific mAb complexes to redirect and improve the efficiency of the primate E complement receptor 1-based clearance reaction to remove a virus from the circulation. As an initial approach, we used bacteriophage phiX174 as an immunologic model for mammalian viruses. Bispecific complexes were prepared by chemically cross-linking a mAb specific for complement receptor 1 with a mAb specific for the bacteriophage phiX174. In a monkey model these complexes facilitate rapid and quantitative binding of the target bacteriophage to E in vitro and in vivo. Moreover, after in vivo binding to E, the complexes containing mAb and prototype virus are rapidly cleared from the circulation of rhesus and cynomolgus monkeys without loss of E. Our findings suggest that bispecific mAb complexes, in concert with primate E complement receptor 1, may have therapeutic utility in the treatment of diseases associated with blood-borne pathogens.

Animals↗
PubMed1997

Site of pulmonary vasodilation by inhaled nitric oxide in microembolic lung injury.

We investigated the site of pulmonary vasodilation and associated effects on gas exchange in response to inhaled NO in acute microembolic lung injury. Pulmonary arterial (Ppa) and effective capillary (Pc') pressures versus cardiac output (Q) plots were generated in anesthetized dogs before and after, successively, (1) embolization with 100 microns glass beads, (2) administration of either a placebo (n = 5) or 80 ppm inhaled NO followed by cyclooxygenase inhibition by aspirin 1 g given intravenously and again 80 ppm inhaled NO (n = 8). Pc' was estimated from the pressure decay curve after pulmonary artery balloon occlusion. Embolism increased pulmonary vascular resistance, with a slight decrease in its precapillary component, from 77 to 66%. NO decreased Ppa at the highest levels of Q, and aspirin increased Ppa at all levels of Q. Neither NO nor aspirin affected Pc'/Q plots or pulmonary shunt. We conclude that pulmonary vascular resistance in microembolic lung injury increases at the periphery of the pulmonary arterial tree, with partial reversibility by inhaled NO and by endogenous products of the cyclooxygenase pathway upstream from the site of effective capillary resistance. Reduced pulmonary vascular tone does not improve gas exchange in this model of acute lung injury.

Animals↗
PubMed1996

Generation and characterisation of stable cell lines expressing recombinant human N-methyl-D-aspartate receptor subtypes.

Transfection of mouse L(tk-) cells with human N-methyl-D-aspartate (NMDA) receptor subunit cDNAs under the control of a dexamethasone-inducible promoter has been used to generate two stable cell lines expressing NR1a/NR2A receptors and a stable cell line expressing NR1a/NR2B receptors. The cell lines have been characterised by northern and western blot analyses, and the pharmacology of the recombinant receptors determined by radioligand binding techniques. Pharmacological differences were identified between the two NMDA receptor subtypes. The glutamate site antagonist D, L-(epsilon)-2-[3H]amino-4-propyl-5-phosphono-3-pentanoic acid ([3H]CGP 39653) had high affinity for NR1a/NR2A receptors (KD = 3.93 nM) but did not bind to NR1a/NR2B receptors. Glycine site agonists showed a 2.6-5.4-fold higher affinity for NR1a/NR2B receptors. Data from radioligand binding studies indicated that one of the cell lines, NR1a/NR2A-I, expressed a stoichiometric excess of the NR1a subunit, which may exist as homomeric assemblies. This observation has implications when interpreting data from pharmacological analysis of recombinant receptors, as well as understanding the assembly and control of expression of native NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed1996

Modulation of 45Ca2+ influx into cells stably expressing recombinant human NMDA receptors by ligands acting at distinct recognition sites.

A 45Ca2+ influx assay has been used to investigate the pharmacology of stably expressed recombinant human NR1a/NR2A and NR1a/NR2B N-methyl-D-aspartate (NMDA) receptors. Inhibition of glutamate-stimulated 45Ca2+ influx by six glycine-site antagonists and inhibition of glycine-stimulated 45Ca2+ influx by five glutamate-site antagonists revealed no significant differences between affinity values obtained for NR1a/NR2A and NR1a/NR2B receptors. The polyamine site agonist spermine showed differential modulation of glutamate- and glycine-stimulated 45Ca2+ influx for recombinant NMDA receptors, inhibiting and stimulating 45Ca2+ influx into cells expressing NR1a/NR2A receptors (IC50 = 408 microM) and NR1a/NR2B receptors (EC50 = 37.3 microM), respectively. The antagonist ifenprodil was selective for NR1a/NR2B receptors (IC50 = 0.099 microM) compared with NR1a/NR2A receptors (IC50 = 164 microM). The effects of putative polyamine site antagonists, redox agents, ethanol, and Mg2+ and Zn2+ ions were also compared between NR1a/NR2A and NR1a/NR2B receptors. This study demonstrates the use of 45Ca2+ influx as a method for investigating the pharmacology of the numerous modulatory sites that regulate the function of recombinant human NMDA receptors stably expressed in L(tk-) cells.

Animals↗
PubMed1996

Measuring expectations for participative decision making among graduating nurses.

This paper reports on the initial stage of a research program that examines decisions nurses expect to participate in and the methods by which they expect to participate. This stage of the research focuses on the development of a scale, the Participative Decision Making Scale for Nurses (PDMSN), to measure expectations for participative decision making (PDM) among graduating nurses. It has four subscales that measure expectations for participation in clinical, unit, hospitalwide, and strategic decisions. The PDMSN was administered to two groups of graduating nursing students. Results indicate that the subscales of the PDMSN have high internal consistency; alpha coefficients in Study 1 and Study 2 ranged from .70 to .85 and from .76 to .90, respectively. Patterns of correlations among the subscales and significant correlations with an alternative scale measuring PDM indicate that it is a valid instrument.

Adult↗
PubMed1995

Structure of the promoter for the human macrophage stimulating protein receptor gene.

The macrophage stimulating protein receptor is a receptor protein tyrosine kinase of the met/hepatocyte growth factor receptor family. Binding of the macrophage stimulating protein to its receptor provokes changes in cell morphology and motility. Here we report the structure of the promoter of the gene coding for this receptor. The major transcription start sites have been identified. The 5' flanking region has characteristics of other receptor tyrosine kinase gene promoters, namely several GC boxes but the absence of a TATA box. Deletion analysis shows that multiple elements are needed for full promoter activity.

Amino Acid Sequence↗
PubMed1995

Complications of fat grafting to the penis.

Fat grafting to the penis has recently become popular in some parts of the country. Surgery is commonly performed in the office, where peer review is lacking or nonexistent. A single case is reported documenting a poor cosmetic and functional result after irregular resorption of grafted fat. The external appearance of the penis remained stable for months, even though later biopsy revealed all the grafted fat to be dead. Analogy with pseudolipoma of Glisson's capsule is provided, showing that dead fat cells can survive for years or even a lifetime without absorption by the body. Several complications are examined in this article, and other potential risks are also discussed. The operation, although technically easy to perform, has many serious potential side effects that should be understood.

Adipose Tissue↗
PubMed1994

Derivation of pulmonary capillary pressure from arterial occlusion in intact conditions.

OBJECTIVE: To investigate the reliability of the pulmonary capillary pressure measurement with the arterial occlusion technique. DESIGN: Prospective, randomized, controlled study on anesthetized animals. SETTING: A cardiopulmonary research laboratory. SUBJECTS: Seven healthy, mongrel dogs. INTERVENTIONS: The animals were anesthetized, and left thoracotomy was performed. A 7-Fr pulmonary artery flotation catheter was inserted to monitor the pulmonary arterial pressure. Arterial flow to the left lower lobe was monitored with a cuff-type flow probe. A laser Doppler flow probe was placed on the surface of the left lower lobe to monitor flow in the microcirculation. MEASUREMENTS AND MAIN RESULTS: Arterial occlusions were performed by inflating the flotation balloon located in the left pulmonary artery. A monoexponential curve was fitted to a stretch of data between 0.2 to 2 secs post-occlusion and extrapolated back toward time zero. Time zero was defined as the instant when a change in the arterial pressure was first observed. When the balloon was inflated, pulmonary arterial flow and pressure decreased simultaneously; flow reached zero after 72 +/- 5 msecs, while pressure decreased rapidly and thereafter continued to decline more slowly. A change of flow in the main artery was followed by a change in microvascular flow with an 80 +/- 20 msec lag. Thus, if flow in the large arteries was at a peak or a nadir, a peak or a nadir flow in the microcirculation would occur 80 msecs later. Therefore, as a first approximation, we estimated that flow in the arterioles stopped 80 msecs after it had reached zero in the main artery. At this instant of time when flow in the arterioles stopped, the pressure across the arterial tree would have equilibrated. We calculated the arterial occlusion pressure at time zero (when pressure or flow began to change), at the time when pressure and flow had fully equilibrated across the arterial tree, and two other selected instants in between. The extrapolated pressure at these four instants were all < 1.1 mm Hg apart. CONCLUSIONS: Back extrapolation of the postarterial occlusion data to 80 msecs after flow in the main artery reached zero, provided a physiologically correct estimate of capillary pressure. This approach would be equivalent to extrapolating to 152 msecs after the initial change in pressure was noted. Thus, precapillary pressure can be accurately estimated by identifying time zero as described above, fitting the data between 0.2 to approximately 2.0 secs to a -single exponential, and calculating the pressure on the curve at 152 msecs. However, under clinical conditions, only time zero is identifiable from the pressure tracings. Our results show that back extrapolation to any point between zero and 152 msecs is acceptable. The breakpoint on the arterial pressure tracing (if discernible) is perhaps most practical because it falls between zero and 152 msecs. In humans, wave transmission time generally would be in the same range, and thus, the same criteria may be applied.

Analysis of Variance↗
PubMed1994

Blood flow, volume, and transit time in the pulmonary microvasculature using laser-Doppler.

Capillary transit time is determined by the ratio of capillary volume to flow rate. Exercise-induced hypoxemia is thought to occur because of the short transit time of erythrocytes in capillaries. The effect of flow rate on capillary volume (recruitment vs. distension) is controversial. In a perfused left lower lobe preparation in canine lungs, we used laser-Doppler flowmetry (model ALF21R) to monitor changes in blood flow, volume, and transit time in the microvasculature near the subpleural surface. Changes in total flow, blood volume, and total transit time (tt) were also measured. The results showed that microvascular volume approached maximum when flow rate was at resting value (0.4 l/min) and pressure in the pulmonary artery was > 6 mmHg relative to the level of the capillaries. In contrast, the total blood volume increased gradually over a wide range of flow rates. When flow increased 4.2 times (from 155 to 650 ml/min), tt decreased from 7.32 to 3.53 s; meanwhile, microvascular flow increased from 6.0 to 12.7 units and microvascular transit time decreased from 3.14 to 1.81 units. The changes in microvascular volume and transit time were essentially independent of whether the venous pressure was higher or lower than alveolar pressure. At very high flow (6-10 times resting value), tt fell gradually to approximately 1 s. Direct monitoring of transit time with the laser-Doppler also revealed a gradual decline in microvascular transit time as flow rate increased from 2 to 10 times the normal flow. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Positive end-expiratory pressure increases capillary pressure relative to wedge pressure in the closed and open chest.

The pulmonary arterial wedge pressure is used as a measure of left atrial pressure and frequently as an estimate of pulmonary capillary pressure. The arterial occlusion concept has recently been used to derive a pressure that is thought to be more representative of capillary pressure (Pcap) than wedge pressure (Pw). The object of this study was to measure the arterial occlusion Pcap at different positive end-expiratory pressure (PEEP) levels and to compare it with Pw. Anesthetized, paralyzed, supine, and mechanically ventilated dogs were instrumented with a Swan-Ganz balloon tip catheter (7F) for monitoring pulmonary arterial pressure (Pa), for measuring cardiac output (CO; thermodilution technique), and for performing the arterial occlusions. The postocclusion tracings were analyzed for Pcap in a conventional manner: exponential fitting of the data during the 2 seconds immediately postocclusion and back extrapolating to the instant of occlusion. Instant of occlusion was defined as the time when the Pa tracing began to deviate from the normal tracing. Pw was averaged from the data between 8 to 10 seconds after the occlusion. Increasing PEEP between 0 to 15 mm Hg caused a gradual decline in cardiac output in the closed and open chest conditions. Despite this decline, all three pressures (Pa, Pcap, and Pw) rose gradually in the closed chest. However, in the open chest, increasing PEEP from 0 to 4.7 mm Hg had no effect on the pressures, but between 4.7 and 13.4 mm Hg of PEEP, Pa and Pcap increased markedly with minimal change in Pw.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Control of BEK and K-SAM splice sites in alternative splicing of the fibroblast growth factor receptor 2 pre-mRNA.

The fibroblast growth factor receptor 2 gene pre-mRNA can be spliced by using either the K-SAM exon or the BEK exon. The exon chosen has a profound influence on the ligand-binding specificity of the receptor obtained. Cells make a choice between the two alternative exons by controlling use of both exons. Using fibroblast growth factor receptor 2 minigenes, we have shown that in cells normally using the K-SAM exon, the BEK exon is not used efficiently even in the absence of the K-SAM exon. This is because these cells apparently express a titratable repressor of BEK exon use. In cells normally using the BEK exon, the K-SAM exon is not used efficiently even in the absence of a functional BEK exon. Three purines in the K-SAM polypyrimidine tract are at least in part responsible for this, as their mutation to pyrimidines leads to efficient use of the K-SAM exon, while mutating the BEK polypyrimidine tract to include these purines stops BEK exon use.

Alternative Splicing↗
PubMed1993

Is nitric oxide released in oleic acid lung injury?

Inhibitors of endothelium-derived nitric oxide synthesis or activity have been reported to enhance hypoxic vasoconstriction in isolated lung preparations. We hypothesized that methylene blue, a guanylate cyclase inhibitor, and N omega-nitro-L-arginine, a nitric oxide synthase inhibitor, would increase pulmonary vascular tone and improve gas exchange in anesthetized and ventilated (inspired O2 fraction 0.4) dogs with oleic acid (OA) lung injury. Mean pulmonary arterial pressure-(Ppa) flow (Q) relationships (generated by a manipulation of venous return, which was increased by opening a femoral arteriovenous bypass or decreased by inflating an inferior vena cava balloon) and gas exchange (evaluated by arterial blood gases and SF6 intrapulmonary shunt determinations) were investigated before and after OA (0.06 ml/kg i.v.) and again after solvent (n = 8), methylene blue (8 mg/kg i.v., n = 10), or N omega-nitro-L-arginine (40 mg/kg i.v., n = 8) in a randomized order. OA administration induced pulmonary hypertension, decreased arterial PO2, and increased intrapulmonary shunt. After OA, solvent had no effect on pulmonary hemodynamics and gas exchange. Both methylene blue and N omega-nitro-L-arginine further increased Ppa at all levels of Q. Only methylene blue, however, improved gas exchange after OA (arterial PO2 from 71 +/- 6 to 89 +/- 12 Torr and intrapulmonary shunt from 44 +/- 6 to 34 +/- 6%, both P < 0.02). These results suggest that nitric oxide is released during OA lung injury and modulates pulmonary hypertension. Whether nitric oxide impairs the regulation of gas exchange in OA lung injury remains uncertain, however.

Amino Acid Oxidoreductases↗
PubMed1992

To find a soul.

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Aged↗