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Biomedical subjects

E Weber

Publications and source records attributed to E Weber.

At least 145 records · Page 8Linked to original sources
PubMed1995

Effects of enteral feedback inhibition on motility, luminal flow, and absorption of nutrients in proximal gut of minipigs.

We wanted to clarify whether the postprandial intestinal feedback control activated by nutrients in the distal gut exerts different effects on motility, transit of digesta, and absorption of nutrients in the proximal gut. Additionally, interrelationships among motility, transit, and absorption were to be elucidated because these relationships have only been investigated in the fasted state. In five minipigs, a 150-cm segment of the proximal jejunum was isolated by two cannulas. Motility of the jejunal segment was recorded by multiple strain gauges and analyzed by computerized methods. Markers (Cr- and Cu-EDTA) were used for the measurement of the flow rate, transit time, and absorption of nutrients. After a meal, the test segment was perfused with 2 kcal/min of an elemental diet over a period of 90 min. A feedback inhibition was activated by infusion of nutrients into the midgut at rates of 1-4 kcal/min. Saline was infused as control. With increasing energy loads infused into the midgut, the motility index and the length of contraction waves decreased, whereas the incidence of stationary contractions increased, ie, the motility changed from a propulsive to a segmenting pattern. These modulations of motility were associated with a linear decrease in the flow rate and a linear increase in transit time. Flow and transit were linearly correlated with each other. Additionally, the reduction in flow rate and the delay in luminal transit were associated with a linear increase in the absorption of nutrients. However, the increase in absorption induced by the feedback mechanism was small (7.3-13.4%) compared to the marked inhibition of the motility parameters (54-64%), the flow rate (59%), and the delay of transit (5.8-fold). Feedback control primarily modulated motor patterns and luminal flow, whereas the small increase in absorption was only a side effect due to the longer contact time of the nutrients with the mucosa.

Animals↗
PubMed1995

[Hyperthyroidism after lithium withdrawal: coincidence or not?].

A 59 year-old manic-depressive woman treated with lithium for 10 years, developed hyperthyroidism three months after lithium withdrawal. The usual side effects on lithium on thyroid function include hypothyroidism and/or development of a goiter. Hyperthyroïdism occurring during lithium therapy is more rarely described. Hyperthyroidism has been exceptionally reported after lithium withdrawal, as in this case (five cases are recorded). The role of lithium in this pathology is controversial. Well-designed prospective studies are needed to clarify this question. Nevertheless, the effects of lithium on the thyroid metabolism are not always harmless and must prompt the clinicians to control the thyroid hormones before, during and after lithium therapy.

Female↗
PubMed1995

HIV prevention beliefs among urban African-American youth.

PURPOSE: This study investigates specific beliefs related to prevention of AIDS and HIV infection among African-American teenagers. METHODS: This study administered valid and reliable measures of HIV/AIDS risk knowledge and prevention beliefs to 150 African-American teenagers. Demographic and psychosocial data were gathered. RESULTS: Black teenagers respond in socially acceptable and undesirable ways and this ambivalence can be explained within the theory of reasoned action. These teens simultaneously believed in the importance of safe sex behaviors while expressing doubt about the viability of some safe sex behaviors. Females demonstrated higher self-efficacy and self-control beliefs while males were more likely to endorse culturally loaded suspicious beliefs about AIDS contraction and transmission. CONCLUSIONS: Those teenagers who perceived themselves as highly knowledgeable scored lower on reliable AIDS Knowledge and Prevention Beliefs measures than those who claimed moderate AIDS knowledge. Some of these "Know It All" teenagers may reflect a subculture of pseudo-confidence that requires special interventions.

Adolescent↗
PubMed1995

In vivo models of cerebral ischemia: effects of parenterally administered NMDA receptor glycine site antagonists.

Both in vitro and in vivo experiments have implicated extracellular glycine in the pathogenesis of ischemic brain damage. Recently, halogenated derivatives of quinoxaline-2,3-dione have been synthesized that possess bioavailability when parenterally administered and minimal psychotomimetic properties. Such compounds have allowed investigation into the efficacy of glycine receptor antagonism as a strategy for protection against cerebral ischemic insults. Rats underwent either 90 min of middle cerebral artery filament occlusion or 10 min of forebrain ischemia with recovery while receiving intraperitoneal injections of either a glycine receptor antagonist (ACEA-1021, ACEA-1031, or ACEA-1011) or vehicle (dimethyl sulfoxide). Both ACEA-1021 and ACEA-1031 reduced cerebral infarct volumes and were associated with a reduced incidence of hemiparesis resulting from MCA occlusion. ACEA-1011, administered in a smaller dose had no effect. In the forebrain ischemia model, glycine receptor antagonism had no effect on delayed neuronal necrosis in the hippocampal CA1 sector, neocortex, or caudoputamen. We conclude that pharmacologic antagonism of glycine at the strychnine-insensitive glycine receptor presents a neuroprotective profile similar to that previously observed for antagonists of glutamate at the N-methyl-D-aspartate complex with a potential for fewer side effects.

Animals↗
PubMed1995

The competitive NMDA antagonist CGP 40116 permanently reduces brain damage after middle cerebral artery occlusion in rats.

In this study we evaluated the effect of the competitive N-methyl-D-aspartate (NMDA) antagonist D-(E)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid (CGP 40116) on both early (2 days) and late (28 days) ischemic brain damage in a rodent model of focal cerebral ischemia by means of magnetic resonance imaging (MRI) and conventional histology. Immediately after occlusion of the left middle cerebral artery (MCA), rats received either CGP 40116 (20 mg/kg i.p.) or isotonic saline. Two MRI scans were performed in each animal 2 and 28 days after MCA occlusion. After the second scan, rats were perfusion fixed for histological evaluation. The volume of lesioned brain tissue as determined by MRI or histology was calculated from the damaged area in single sections and the distance between them. CGP 40116 reduced acute infarct volume as measured by MRI 2 days after MCA occlusion by 44% (p < 0.05, analysis of variance). After 28 days the lesion detected by MRI was still significantly smaller in the drug-treated animals. This finding was confirmed by the histological analysis showing a 64% reduction in the volume of brain atrophy in the CGP 40116 group (p < 0.05, analysis of variance). There was a good correlation between the MRI data and the results of the histological evaluation (r = 0.9). Our results indicate that (a) the competitive NMDA antagonist CGP 40116 permanently protects brain tissue from the consequences of cerebral ischemia in a rat model for human stroke and (b) early and late pathological changes can be accurately measured by MRI.

2-Amino-5-phosphonovalerate↗
PubMed1995

Radiation studies on B cell differentiation marker CD24/SCLC Cluster-4 antigen expressing and non-expressing lung cancer cell lines and mouse fibroblasts.

A correlation between CD24 expression and higher intrinsic radiation sensitivity has been described in B-lineage acute lymphoblastic leukaemia (B-ALL). We recently identified the SCLC surface antigen Cluster-4 (CL-4) to be identical to the B cell differentiation marker CD24, except for one amino acid residue. The CD24/CL-4 antigen is highly expressed on SCLC, but rarely on NSCLC cells. In order to investigate the influence of the expression of CD24/CL-4 on the radiation sensitivity in a non-leukaemic cell system, sublines of the human SCLC H249 cell line transfected with mutated ras oncogene, and differing in their CD24/CL-4 expression, were studied. In addition, we stably transfected the NSCLC A125 cell line and the mouse fibroblast NIH3T3 cell line with the CL-4 cDNA. The differential expression of CD24/CL-4 on the cells had no influence on morphology, proliferation and cloning efficiency. Radiation studies were done with cells in exponential growth phase. In the highly resistant NSCLC A125 cells no difference in radioresponsiveness was observed between CD24/CL-4 expressing and non-expressing cells. In the rather radiosensitive cells, similar responses to radiation were observed between CD24/CL-4 expressing and non-expressing SCLC H249-ras cells, whereas the CL-4 transfected NIH3T3 mouse fibroblasts showed a substantially higher radioresistance than the CD24/CL-4 non-expressing control cells. In conclusion, the correlation between CD24/CL-4 expression and radiation sensitivity is controversial and depends on the cell type.

3T3 Cells↗
PubMed1995

Mandatory toxicology testing and chemical dependence consultation follow-up in a level-one trauma center.

OBJECTIVE: There is a growing body of evidence indicating an association between intoxication and major trauma. This study assessed the prevalence of alcohol or drug intoxication in major trauma admissions to an urban trauma center. DESIGN: Sequential case series. METHODS: Toxicology testing and structural clinical interview assessment. MAIN RESULTS: Seventy-eight percent of patients tested had positive toxicology results. Chemical dependence assessments performed on patients who tested positive revealed that 94% met the criteria for a substance dependence or abuse disorder. CONCLUSIONS: The implications of this data for admission toxicology testing policies and chemical dependence consultation support services to trauma units are discussed.

Alcohol Drinking↗
PubMed1995

Abdominal pain: do not forget Thorotrast!

The use of Thorotrast (25% thorium dioxide), a radiologic contrast agent used up until the mid-1950s, was associated with a wide range of malignancies, mainly of hepatic origin. We report a case of Thorotrast-induced hepatocarcinoma in an 82-year-old woman.

Aged↗
PubMed1995

The small cell lung cancer antigen cluster-4 and the leukocyte antigen CD24 are allelic isoforms of the same gene (CD24) on chromosome band 6q21.

Cluster-4 and CD24 cDNA's have recently been cloned from the small cell lung carcinoma (SCLC) cell line SW2 and from the erythroleukemia cell line K562, respectively. The only difference in the coding sequence, between cluster-4 and CD24 antigens is the substitution of a single base pair leading to a substitution of Val by Ala near the putative glycosylphosphatidylinositol (GPI) anchorage sites of the mature protein. Here we demonstrate that the nucleotide substitution which distinguishes the cluster-4 and CD24 antigen genes is due to an allelic polymorphism on chromosome band 6q21. In addition, we identified by Southern blotting and PCR of DNA from somatic human x hamster hybrid cell lines homologues of cluster-4/CD24 on the Y chromosome and chromosome 15. We suggest, however, that the gene on 6q21 is the active locus since the mRNA of cell lines always represents the allelic variants found on chromosome 6. The distribution pattern of this allelic polymorphism in SCLC cell lines and leukocytes of healthy donors did not reveal any obvious relationship with disease. However, it is noteworthy that homozygosity for cluster-4 was found in only one case whereas heterozygosity and homozygosity for CD24 both contribute up to 50% of the samples examined.

Alleles↗
PubMed1995

Nonstructural protein 2 (NS2) of respiratory syncytial virus (RSV) detected by an antipeptide serum.

The human respiratory syncytial virus (RSV) is often associated with airway obstruction and is suspected to induce bronchial hyperreactivity. Interactions of viral proteins with cellular components may be responsible for epithelial damage leading to bronchial hyperreactivity. In this study, we describe the localization of the 14.7-kD nonstructural protein 2 (NS2) in RSV-infected cells. The detection of NS2 was performed using antipeptide antibodies elicited against amino acids 109-123 of the predicted sequence of the NS2 protein. By using recombinant NS2, we could clearly demonstrate the specificity of the antipeptide antibodies. With this defined tool, NS2 could be first detected in infected HEp-2 cells at 10 h p.i. subsequently to the detection of N protein. In double-staining experiments, colocalization of NS2, P protein and N protein was demonstrated. The antipeptide antibodies recognized the NS2 protein in the sediment of RSV-infected HEp-2 cells lysed with RIPA buffer at 48 h p.i. The results agree with the reported interaction of RSV with cytoskeletal intermediate filaments. These interactions may implicate essential cellular functions suspected to induce bronchial hyperreactivity.

Amino Acid Sequence↗
PubMed1995

[Evaluation of laxity, rigidity and compliance of the normal and pathological knee. Application to survival curves of ligamentoplasties].

PURPOSE OF THE STUDY: The aim of this prospective study was to measure the stiffness of the ACL in normal knees, ACL deficient knees and after ACL reconstructions or meniscectomies. Stiffness is a physical quantity which expresses objectively the mechanical efficiency of the ACL. MATERIAL AND METHODS: 1502 tests were performed on: 480 normal control knees, 191 acute tears and 171 chronic instabilities pre and post-operatively, 60 extra-articular plasties, 30 meniscectomies and 64 arthritic knees before and after a cruciate sparing arthroplasty. The force displacement measurements were made on radiograms of the medial and lateral compartment of each knee at 20 degrees flexion by applying a postero anterior force from 0 to 300 N with increments of 50 N. The stiffness is the slope of the F/dl curve. RESULTS: In the normal knee the medial compartment is fixed. Its stiffness is 13.8 x 10(4) N/m and does not depend on age and sex. The diagnosis of ACL rupture is made when the right/left difference on the medial compartment is at least 4 mm at 250 N. The lowest level for an accurate diagnostic is 180 N. The positive predictive value is 99 per cent. In acute tears the stiffness is 2.5 x 10(4) N/m. It is 3.4 x 10(4) N/m in chronic instability (p = 0.0001). When a meniscectomy was performed in chronic instability the stiffness decreases significantly (M+: 3.7 x 10(4) N/m; M-: 2.1 x 10(4) N/m) (p = 0.03). After a bone-patellar tendon-bone plasty (BPTB) the stiffness was 6.0 x 10(4) N/m and did not decrease with the passage of time but after the extra-articular plasty (EAP) the stiffness was 4.7 x 10(4) N/m after 24 months and 3.0 x 10(4) N/m after 60 months. Meniscectomy decreases the stiffness in both procedures, however it remains stable after BPTB, but decreases with the passage of time after EAP. DISCUSSION: Stiffness is a biomechanical parameter of knee ligaments. It is highly correlated with the clinical symptoms of instability (p = 0.0001). It is more accurate than laxity which is a numerical value without mechanical significance. CONCLUSION: This method gives functional information on the ACL deficient knee. It is the more precise method for the diagnostic of ACL rupture with an efficiency of 98.5 per cent. It has a high prognostic value after ACL surgery and can be considered as the mechanical survival of the plasty.

Adolescent↗
PubMed1995

In vitro pharmacology of ACEA-1021 and ACEA-1031: systemically active quinoxalinediones with high affinity and selectivity for N-methyl-D-aspartate receptor glycine sites.

N-methyl-D-aspartate (NMDA) receptor antagonists show therapeutic potential as neuroprotectants, analgesics, and anticonvulsants. In this context, we used electrical recording techniques to study the in vitro pharmacology of two novel quinoxalinediones, i.e., ACEA-1021 and ACEA-1031 (5-nitro-6,7- dichloro- and 5-nitro-6,7-dibromo-1,4-dihydro-2,3-quinoxalinedione, respectively). Assays with NMDA receptors expressed by rat brain poly(A)+ RNA in Xenopus oocytes and with NMDA receptors in cultured rat cortical neurons indicated that ACEA-1021 and ACEA-1031 are potent competitive antagonists at NMDA receptor glycine sites. Apparent dissociation constants (Kb values) for ACEA-1021 and ACEA-1031 ranged between 6 and 8 nM for oocyte assays and between 5 and 7 nM for neuronal assays. Cloned NMDA receptors expressed in oocytes showed up to 50-fold variation in sensitivity, depending upon subunit composition. For example, using fixed agonist concentrations (10 microM glycine and 100 microM glutamate) IC50 values for ACEA-1021 with four binary combinations were as follows: NMDA receptor (NR)1A/2A, 29 nM; NR1A/2B, 300 nM; NR1A/2C, 120 nM; NR1A/2D, 1500 nM. Measurement of EC50 for glycine and calculation of Kb for the inhibitors indicated that differences in IC50 values are due to subunit-dependent variations in glycine affinity (EC50 ranged between approximately 0.1 and 1 microM) combined with variations in affinity of the antagonists themselves (Kb of approximately 2-13 nM). In addition to the strong antagonism of NMDA receptors, ACEA-1021 and ACEA-1031 were also moderately potent competitive inhibitors of non-NMDA receptors activated either by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid or by kainate. Antagonist affinities were similar whether measured with receptors expressed by rat brain poly(A)+ RNA in oocytes (Kb of 1-2 microM) or with cultured neurons (Kb of 1.5-3.3 microM). Our results suggest that the in vivo neuro-protective actions of ACEA-1021 and ACEA-1031 are predominantly due to inhibition at NMDA receptor glycine sites, although additional inhibition at non-NMDA receptors may play an ancillary role.

Animals↗
PubMed1995

Pharmacology of 5-chloro-7-trifluoromethyl-1,4-dihydro-2,3-quinoxalinedione: a novel systemically active ionotropic glutamate receptor antagonist.

5-Chloro-7-trifluoromethyl-1,4-dihydro-2,3-quinoxalinedione (ACEA-1011) has analgesic properties in animal models of tonic pain. To investigate the mechanisms underlying this effect we used electrical recording techniques to characterize the in vitro pharmacology of ACEA-1011 at mammalian glutamate receptors. Two preparations were used: Xenopus oocytes expressing rat brain receptors and cultured rat cortical neurons. Results showed that ACEA-1011 is a competitive antagonist at NMDA receptor glycine sites. Apparent antagonist affinities (Kb values) were 0.4 to 0.8 microM in oocytes and approximately 0.6 microM in neurons. IC50 values for ACEA-1011 against four binary subunit combinations of cloned rat NMDA receptors (NR1A/NR2A, 2B, 2C or 2D) ranged from 0.4 to 8 microM (1 microM glycine). The 20-fold variation in sensitivity was due to a combination of subunit-dependent differences in glycine and antagonist affinities; EC50 values for glycine ranged between 0.08 to 0.8 microM and Kb values for ACEA-1011 between 0.2 to 0.8 microM. In addition, ACEA-1011 inhibited AMPA-preferring non-NMDA receptors by competitive antagonism at glutamate binding sites. Kb values were 4 to 9 microM in oocytes and 9 to 10 microM in neurons. The ED50 for ACEA-1011 in a mouse maximum electroshock-induced seizure model was approximately 12 mg/kg i.v.. Our results indicate that ACEA-1011 is a systemically active broad selectivity ionotropic glutamate receptor antagonist.

Analgesics↗
PubMed1994

Morphine analgesia and tolerance in mice selectively bred for divergent swim stress-induced analgesia.

Morphine-induced analgesia and tolerance were examined in Swiss Webster mice selectively bred for high and low swim stress-induced analgesia. Morphine produced a dose-dependent analgesia in both lines; it was 4-fold more potent in the high analgesia line than in the low analgesia line. Despite the differences in morphine-induced analgesia, the degree of tolerance was the same in both lines. Together, these data suggest that selective breeding of mice for high and low swim stress-induced analgesia produced a striking difference in morphine-induced analgesia without affecting the degree of tolerance. Thus, while there is a common genetic determination in swim stress-induced and morphine-induced analgesia, the development of tolerance to morphine possibly relies on a different genetic background.

Analgesia↗