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D Pape

Publications and source records attributed to D Pape.

At least 37 records · Page 2Linked to original sources
PubMed1999

An encyclopedia of mouse genes.

The laboratory mouse is the premier model system for studies of mammalian development due to the powerful classical genetic analysis possible (see also the Jackson Laboratory web site, http://www.jax.org/) and the ever-expanding collection of molecular tools. To enhance the utility of the mouse system, we initiated a program to generate a large database of expressed sequence tags (ESTs) that can provide rapid access to genes. Of particular significance was the possibility that cDNA libraries could be prepared from very early stages of development, a situation unrealized in human EST projects. We report here the development of a comprehensive database of ESTs for the mouse. The project, initiated in March 1996, has focused on 5' end sequences from directionally cloned, oligo-dT primed cDNA libraries. As of 23 October 1998, 352,040 sequences had been generated, annotated and deposited in dbEST, where they comprised 93% of the total ESTs available for mouse. EST data are versatile and have been applied to gene identification, comparative sequence analysis, comparative gene mapping and candidate disease gene identification, genome sequence annotation, microarray development and the development of gene-based map resources.

Animals↗
PubMed1999

Endothelin, but not angiotensin II, contributes to the hypoxic contractile response of large isolated pulmonary arteries in the rat.

UNLABELLED: The aims of this study were to investigate whether angiotensin II and/or endothelin could contribute to the hypoxic contractile response of isolated rat pulmonary artery. Experiments were performed for 1 h on noradrenaline precontracted arterial rings in hypoxic conditions (95% N2 and 5% CO2). Nicardipine, lisinopril, losartan, phosphoramidon, FR139317 and bosentan were used to block Ca2+ channels, angiotensin I-converting enzyme, AT1 receptors, endothelin-converting enzyme, ETA receptors, and ETA/ETB receptors, respectively. The profile of the hypoxic contractile response was biphasic, displaying, after a short relaxation, a weak and transient contraction (from 2-4 min) and then, before complete relaxation, a slowly developed but sustained contraction (from 14-60 min). Endothelium removal abolished the transient contraction and reduced (-59%) the sustained contraction. Nicardipine did not modify the transient contraction, but concentration-dependently decreased (from -35% to -100%) the sustained contraction (P = 0.024). Lisinopril and losartan did not affect the response (P = 0.418 and P = 0.973, respectively). Bosentan did not modify the transient contraction, but concentration-dependently decreased (from -14% to -71%) the sustained contraction (P = 0.016), whereas phosphoramidon and FR139317 did not affect the response (P = 0.830 and P = 0.806, respectively). CONCLUSIONS: In rat, (i) both phases of the hypoxic contractile response are endothelium-dependent and independent of angiotensin II; (ii) the transient contraction does not depend on endothelin; (iii) the sustained contraction, which involves calcium influx, appears partly dependent on mature endothelin released from storage granules by stimulating ETB receptors.

Angiotensin I↗
PubMed1997

Hypoxic contractile response in isolated rat thoracic aorta: role of endothelium, extracellular calcium and endothelin.

The effects of hypoxia on isolated arteries remain controversial, depending on the species, vascular beds and protocols. The aims of the study were to characterize the response of rat thoracic aorta to hypoxia and to examine the roles of endothelium, extracellular calcium and endothelin in this response. Hypoxia was induced by bubbling Krebs solution with 95% N2 and 5% CO2 instead of 95% O2 and 5% CO2. Experiments were performed during 1 h in norepinephrine (0.01 microM) precontracted rings. Hypoxia produced a biphasic response consisting of an initial transient partial relaxation (67% at 14 min) followed by a slow but sustained contraction (27% from 40 to 60 min). After endothelium removal, relaxation appeared faster with increased magnitude (82% at 12 min) and was followed by a weak transient contraction (16% at 25 min). In endothelium-intact rings, Ca2+ free medium (EGTA, 0.1 mM) and Ca2+ channel blockers, verapamil (0.05, 0.5 and 5 microM) or nicardipine (0.1, 1 and 10 microM), had no effect on relaxation but inhibited the contraction, the effects of both calcium antagonists being concentration-dependent. Similarly, the ETA/ETB receptor antagonist, bosentan (0.1, 10 and 1,000 nM), induced a concentration-dependent decrease in the contraction. We conclude that 1) the response of rat thoracic aorta during 1 h of hypoxia is biphasic (relaxation followed by contraction); 2) the endothelium is involved in the contraction whereas its role in the relaxation remains to be elucidated; 3) extracellular calcium is involved in the contraction; and 4) endothelin may play a role in the contraction.

Animals↗
PubMed1996

[The dynamic hip screw with support plate--a reliable osteosynthesis for highly unstable "reverse" trochanteric fractures?].

ORIF management of unstable trochanteric fractures of type A3 of the A0 classification is difficult because of lateral dislocation of the proximal fractured segments, particularly when only the sliding hip-screw is used for fixation. A connectable butt-press plate was recently developed in order to prevent this type of dislocation. We review the results with this fixation technique in 22 elderly patients with an average age of 76 years who presented with highly unstable trochanteric fracture of the A3 type. Three patients died of diseases unrelated to the trauma or operation before the fractures had healed. The other 19 were followed prospectively until fracture healing had occurred. Complaints, leg shortening and changes in the CCD angle were recorded. Furthermore, the mobility score was determined. Although the patients were able to bear full weight after the operation, no lateral dislocation of fragments was observed. Only 1 patient had a varus dislocation of 5 degrees until the fracture had consolidated. This was due to severe osteopenia and subsequent dislocation of the screw within the femoral head. No pseudarthrosis, osteitis or rotational malalignment was noted. Five of the surviving patients had a lower mobility score after fracture healing as compared to the status before the fracture was sustained. On the basis of this review, we recommend the use of this new connectable buttress plate with sliding hip screws because it provides sufficient fixation of highly unstable fractures of type A3.

Aged↗
PubMed1996

Noninterchangeability of specific radioimmunoassay and monoclonal antibody fluorescent polarization immunoassay in cyclosporine measurements.

This study compares cyclosporine (CsA) concentrations in whole blood from patients receiving bone marrow (n = 10), renal (n = 48), heart (n = 50) or liver (n = 50) transplants, as measured by monoclonal antibody flurorescence polarization immunoassay (FPIA) and specific 125I-radioimmunoassay (RIA). The FPIA overestimated CsA by an average of 25%. Results were higher for all indications: FPIA/RIA ratios were 1.17 for bone marrow, 1.23 for renal and 1.27 for both heart and liver transplants, and these values were significantly different from 1.0. The percentage of overestimation was higher at low CsA concentrations (< or = 100 micrograms/L) than at high CsA concentrations (> or = 400 micrograms/L). In all indications, results by both methods correlated well (r > 0.96) but slopes and intercepts were different from 1.0 and 0.0, respectively, and these parameters varied greatly between the grafted populations. These findings obtained with the two methods could not be attributed to matrix effect because the mean FPIA/RIA ratio for spiked control samples was 1.0. The discrepancy between the FPIA and RIA could be explained by the lower specificity of the monoclonal antibody contained in the FPIA kit. These results suggest that FPIA is not as accurate as RIA and that the two methods are not interchangeable in CsA level measurement.

Antibodies, Monoclonal↗
PubMed1996

Study of the mechanisms involved in adenosine-5'-O-(2-thiodiphosphate) induced relaxation of rat thoracic aorta and pancreatic vascular bed.

1. The endothelium-dependent relaxation of blood vessels induced by P2Y-purinoceptor activation has often been shown to involve prostacyclin and/or nitric oxide (NO) release. In this work, we have investigated the mechanisms involved in the relaxant effect of the P2Y agonist, adenosine -5'-O-(2-thiodiphosphate) (ADP beta S) using two complementary preparations: rat pancreatic vascular bed and aortic ring. 2. On the pancreatic vascular bed, ADP beta S (1.5 and 15 microM) infused for 30 min induced a concentration-dependent vasodilatation; it was progressive during the first 10 min (first period) and sustained from 10 to 30 min (second period). Indomethacin (10 microM) delayed ADP beta S-induced vasodilatation (1.5 and 15 microM) by about 6 min. N omega-nitro-L-arginine methyl ester (L-NAME) (200 microM) suppressed the relaxation for about 5 min but thereafter ADP beta S at the two concentrations progressively induced an increase in the flow rate. Even the co-administration of L-NAME and indomethacin did not abolish the ADP beta S-induced vasorelaxation. 3. On 5-hydroxy tryptamine (5-HT) precontracted rings mounted in isometric conditions in organ baths, we observed that ADP beta S induced a concentration-dependent relaxation of rings with a functional endothelium; this effect was stable for 25 min. The ADP beta S relaxant effect was strongly inhibited by Reactive Blue 2 (30 microM) and was suppressed by pretreatment of rings with saponin (0.05 mg ml-1 for 30 min), which also abolished the acetylcholine-induced relaxation. 4. ADP beta S-induced relaxation of 5-HT precontracted rings is largely inhibited by indomethacin (100 or 10 microM) or L-NAME (100 microM). 5. We conclude that: the ADP beta S-induced relaxation is endothelium-dependent, mediated by P2Y-purinoceptors, and at least in part linked to NO and prostacyclin release, depending on the preparation used. Furthermore, on the pancreatic vascular bed, (an)other mechanism(s) than prostacyclin and NO releases may be involved in ADP beta S-induced vasodilatation.

Adenosine Diphosphate↗
PubMed1996

[Multiple organ failure after severe trauma: predictable by the MEGX liver function test?].

The prognostic value of a dynamic liver-function test, based on the hepatic conversion of lidocaine to monoethylglycinexylidide (MEGX), in predicting multiple organ failure (MOF) was prospectively investigated in 28 critically ill patients after multiple trauma. The MEGX test and conventional static liver tests (bilirubin, aspartate aminotransferase, glutamate dehydrogenase and factor V) were performed on days 1, 3, 5, and 7 after trauma and patients were classified by a modified MOF score into a group without (n = 18) and a group with the MOF syndrome (n = 9). All patients who subsequently developed MOF, however, displayed a sharp decrease in their MEGX values between days 1 and 3.

Alanine Transaminase↗
PubMed1995

Monoethylglycinexylidide as an early predictor of posttraumatic multiple organ failure.

The prognostic value of a dynamic liver-function test, based on the hepatic conversion of lidocaine to monoethylglycinexylidide (MEGX), in predicting multiple organ failure (MOF) was prospectively investigated in 28 critically ill patients after multiple trauma. The MEGX test and conventional static liver tests (bilirubin, aspartate aminotransferase, glutamate dehydrogenase, and factor V) were performed on days 1, 3, 5, and 7 after trauma. Patients were classified by a modified MOF score into a group without (n = 18) and a group with the MOF syndrome (n = 10). One patient who developed MOF on the basis of a bacterial septicemia was excluded from the general evaluation. No significant differences were observed in the MEGX values of the two groups on day 1. All patients who subsequently developed MOF, however, displayed a sharp decrease in their MEGX values between days 1 and 3. Analysis of the data using receiver operating characteristic (ROC) curves revealed that the results of the MEGX test on day 3 provided the greatest discriminating power between patients with and without subsequent MOF. A cut-off MEGX value of 30 micrograms/L on day 3 was associated with a prognostic sensitivity of 89% and a prognostic specificity of 94%.

Adult↗
PubMed1994

Induction of circulating soluble tumour necrosis factor receptor and interleukin 1 receptor antagonist following interleukin 1 alpha infusion in humans.

The aim of this study was to investigate circulating levels of tumour necrosis factor soluble receptor p55 (TNFsrp55) and interleukin 1 receptor antagonist (IL-1ra) in cancer patients undergoing treatment with IL-1 alpha. Patients were treated with 0.03 micrograms/kg IL-1 alpha administered intravenously over a 30 min interval daily for five consecutive days. Plasma TNFsrp55 levels rose dramatically and peaked (24.5 +/- 3.6 ng/ml) within 1 h after the first IL-1 alpha infusion. Thereafter, the levels rapidly declined and reached baseline levels within 24 h. The increases observed on days 3 and 5 of treatment were less pronounced but the reductions in peak levels were not statistically significant. IL-1ra levels increased less abruptly after an IL-1 alpha infusion than did TNFsrp55 levels and peaked (25.3 +/- 5.1 ng/ml) within 2 h of the start of the IL-1 alpha infusion. Levels then rapidly declined reaching baseline values within 24 h. As with TNFsrp55 levels, peak IL-1ra levels observed on days 3 and 5 of treatment were less than those measured on day 1. IL-1 alpha and IL-1 beta levels were consistently below the threshold of detection of the RIAs employed in these studies. Likewise, with the exception of a single time point in one of the four patients studied, TNF-alpha was undetectable in all plasma samples assayed.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclophosphamide↗
PubMed1993

A method for the detection of erythrocyte-bound interleukin-8 in humans during interleukin-1 immunotherapy.

Interleukin-8 (IL-8) has been recently shown to bind to human erythrocytes with high affinity and is therefore potentially difficult to detect in serum or plasma. IL-8 is transiently elevated in the serum of baboons after the administration of interleukin-1 alpha (IL-1 alpha). The objective of this study was to investigate whether IL-8 can be detected in the plasma or in detergent-lysed erythrocytes from cancer patients undergoing treatment with IL-1 alpha. Using a specific radioimmunoassay (RIA), plasma IL-8 was detected within 1-2 h after the first IL-1 alpha infusion. Thereafter, the levels declined rapidly and after 4-8 h were undetectable. Erythrocyte-bound IL-8 was detectable 1-2 h after the increase in plasma levels. The erythrocyte-bound IL-8 levels were higher than those measured in plasma and remained elevated long after the plasma levels had become undetectable. Erythrocyte membranes accounted for all of the erythrocyte-associated IL-8, as IL-8 was undetectable in the cytosol after erythrocyte lysis. The assay used in these studies detects IL-8 in erythrocyte lysates when it cannot be measured in plasma and may therefore be useful in monitoring IL-8 production in vivo.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

An experimental investigation of thought suppression.

An experiment investigating the hypothesis that trying to suppress a thought will lead to an immediate and/or delayed increase in its occurrence is reported. Normal subjects listened to a taped story and then verbalized their stream of consciousness during two consecutive time periods. During the first period, one group (suppression) were asked not to think about the tape while two other groups (controls) were asked to think about anything or think about anything including the tape. During the second period, all three groups were instructed to think about anything. Results from the first period failed to support the immediate enhancement hypothesis as the suppression group reported less thoughts about the tape than the controls. However, results from the second period supported the delayed (rebound) hypothesis as subjects who had previously suppressed reported more thoughts about the tape than subjects who had not. The theoretical, methodological, and clinical implications of these results are discussed.

Adult↗
PubMed1991

[Improvement in blood lipids and lipoproteins by simple nutritional modification, exemplified by a high-fiber modified so-called "heart diet" of a West German clinic: the therapeutic gain due to expanding and high fiber foods].

In a clinical study with 40 patients with cardiovascular disease or severe hypercholesterolamia is shown the beneficial cholesterol-lowering effect of a high fibre diet with a high part of soluble plant fibres (pectines, beta-glucanes, psyllium hydrophilic mucilloid). This by fibre content selectet nutrition was integrated in a so called "prudent heart diet" over 3 to 33 weeks. Total cholesterol was lowered from 356 mg/dl (in average) to 246 mg/dl (-20.3%), APO B from 126.3 mg/dl to 103.1 mg/dl (-15.2%) triglycerides from 251 mg/dl to 222 mg/dl (-11.8%) HDL-cholesterol increased from 46 mg/dl to 49 mg/dl (+7.6%), APO A-I from 123 mg/dl to 136 mg/dl (+10.1%).

Adult↗
PubMed1989

Comparative evaluation of scavenger properties of exifone, piracetam and vinburnine.

The involvement of radical reactions in the ageing process, physiological as well as pathological, is well demonstrated. It is accepted that alloxan cyto-toxicity is linked to a production of hydroxylated free radicals and that a substance preventing the development of alloxanic diabetes possesses scavenger properties. The objective of this work was to demonstrate, in this model, the anti-radical effect of 3 molecules recommended in the treatment of cerebral insufficiency and a reference substance (+)-catechin. We observed a protective action with catechin (P less than 0.05) at the highest dose (100 mg/kg). PEG alone was moderately active but comparison of PEG-alloxan and PEG-exifone-alloxan showed a highly significant difference (P less than 0.001) at the two highest doses (60 and 120 mg/kg). Piracetam (200 and 400 mg/kg) and vinburnine (7.5 and 15 mg/kg) were inactive. Under these experimental conditions, exifone demonstrated remarkable anti-radical properties.

Animals↗
PubMed1988

Randomized, double-blind trial of exifone versus cognitive problems in Parkinson's disease.

Exifone is a novel substance of the benzophenone group that possesses potent scavenging properties. Initial findings demonstrate beneficial effects on age-related cognitive disorders. In this double-blind clinical trial versus placebo, the efficacy of 2 dosages (600 and 1200 mg/d) was evaluated with regard to Parkinson's disease (PD)-related cognitive disorders, for which there is increasing suspicion of a free-radicals origin. Despite disparities between the treatment groups as assessed by validated scales and subtests, and a considerable placebo effect on main parameters, both dose levels of exifone produced statistically significant improvement of the cognitive items most commonly impaired by PD: immediate recall, naming of objects presented, spatiotemporal orientation, and calculation. These properties suggest a new slot for exifone in the range of therapeutics available.

Aged↗
PubMed1985

Comparison of the influence of dihydroergotoxine on cerebral oxygenation in the normoxic and hypercapnic hypoxic dog.

50 bastard dogs are anesthetized by chloralose (100 mg/kg) and mebubarbital (5 mg/kg) and then perfused by three-different dosages of dihydroergotoxine (DHET) (1.25; 2.5; 5 micrograms/kg/min). The effect of DHET on cerebral oxygenation is analyzed under two conditions: normoxia and hypercapnic hypoxia. The following biochemical and physiological parameters are studied: mean vertebral flow (MVF), aortic arterial pressure (AP), heart rate (HR); pO2, pCO2, total CO2, pH, haemoglobin saturation ratio, both in arteries and veins. Other parameters are calculated: O2 arterio-venous difference, CMRO2, O2 extraction coefficient, cerebral O2 supply, vertebral resistance. Under normoxia, DHET, whatever the dosage, induces a decrease of the MVF associated with an inconstant decrease of oxygen supply. At 2.5 micrograms/kg/min, a permanent and significant increase of CMRO2 is obtained. At 5 micrograms/kg/min, similar results are obtained although the decrease of HR and AP is more pronounced. Under hypoxia, the arterio-venous oxygen content difference and the CMRO2 are increased by DHET (2.5 micrograms/kg/min) without any repercussions on AP and MVF (hypothetical role of the blood pH decrease). In conclusion, DHET doubles the CMRO2, as a consequence of an increase of the oxygen extraction ratio. A 2.5 micrograms/kg/min dosage is by itself able to give this maximum effect without any major consequences on HR, AP and MVF. This effect is still obtained in hypoxia without any peripheral vascular effect.

Animals↗
PubMed1984

Impairment of acquired temporal response regulation of rats under normobaric hypoxia.

Effects of hypoxia on learning involving temporal regulation of behaviour was investigated. Under 10% hypoxia there was a decrease in the number of conditioned responses, and the 'efficiency' of reinforcement, but no modification of temporal discrimination. Normobaric hypoxia may be a useful model for studying certain behavioural and pharmacological effects of cerebral circulatory insufficiency, and their implications at the level of the central nervous system, but it would be incorrect to use such a model to study factors that might prevent the loss of acquired knowledge.

Animals↗