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Biomedical subjects

G Muller

Publications and source records attributed to G Muller.

At least 37 records · Page 2Linked to original sources

Signatures of quantum integrability and nonintegrability in the spectral properties of finite hamiltonian matrices

For a two-spin model which is (classically) integrable on a five-dimensional hypersurface in six-dimensional parameter space and for which level degeneracies occur exclusively (with one known exception) on four-dimensional manifolds embedded in the integrability hypersurface, we investigate the relations between symmetry, integrability, and the assignment of quantum numbers to eigenstates. We calculate quantum invariants in the form of expectation values for selected operators and monitor their dependence on the Hamiltonian parameters along loops within, without, and across the integrability hypersurface in parameter space. We find clear-cut signatures of integrability and nonintegrability in the observed traces of quantum invariants evaluated in finite-dimensional invariant Hilbert subspaces. The results support the notion that quantum integrability depends on the existence of action operators as constituent elements of the Hamiltonian.

Journal Article↗

Electroencephalographic characterization of brain dopaminergic stimulation by apomorphine in healthy volunteers.

Apomorphine, a dopamine receptor agonist (given in a dose of 0.75 mg s.c.), was administered to 8 healthy volunteers; electroencephalograph (EEG) and event-related potential (ERP) mapping were performed before dosing and 0.5, 1.5 and 2.5 h after dosing. Apomorphine caused an overall increase in beta activity at time 0.5 h in both absolute and relative energy; P300 and CNV ERPs were not significantly altered, although a tendency towards increased P300 latency was seen. The results confirm that the EEG mapping technique is sufficiently sensitive to monitor dopaminergic neurochemical stimulation by means of apomorphine. This could lead to a new, non-invasive and repeatable method for monitoring central neuronal systems which is more convenient to apply repeatedly than for example positron emission tomography techniques. Furthermore, electrophysiological techniques undoubtedly constitute an alternative to classical neuroendocrinological methods, allowing a more direct assessment of central nervous system neurotransmission. Finally, these EEG approaches could lead to better characterization of drugs acting on dopaminergic pathways, such as antipsychotics.

Adult↗

CC-3052: a water-soluble analog of thalidomide and potent inhibitor of activation-induced TNF-alpha production.

The immunomodulatory drug thalidomide has been shown to be clinically useful in a number of situations due to its ability to inhibit TNF-alpha synthesis. However, its use is restricted by potentially serious side effects, including teratogenicity and neuorotoxicity; furthermore, insolubility may present problems in terms of systemic bioavailability. Recently, structural modifications of thalidomide have been designed enabling greatly enhanced anti-TNF-alpha activity in LPS-treated mice. In contrast to thalidomide (LPS-induced TNF-alpha IC50 approximately 200 microM in DMSO) and other analogs tested, one of these compounds, CC-3052 (IC50 approximately 1 microM in water), is water soluble. Furthermore, this analog exhibits increased stability in human plasma (t(1/2) approximately 17.5 vs 1.5 h for thalidomide) and appears to be nontoxic, nonmutagenic, and nonteratogenic. At pharmacologically active levels, cellular proliferation and LPS-induced IL-6 mRNA and IL-12p40 mRNA (as well as IL-1beta and IL-6 protein levels) in whole blood cultures were not affected; apparent inhibition of NK activity by CC-3052 was reversed upon addition of exogenous rTNF-alpha. In addition, IL-10 mRNA and protein levels were increased. These properties are consistent with results indicating inhibition of phosphodiesterase type IV activity by CC-3052. Furthermore, CC-3052 did not increase the degradation rate of macrophage TNF-alpha transcripts nor inhibit LPS-induced primary macrophage NF-kappaB activation. Taken together, the potency of selective TNF-alpha inhibition, water solubility, and increased plasma stability make CC-3052 an excellent candidate for further development and clinical evaluation for the treatment of TNF-alpha-mediated disease.

Adjuvants, Immunologic↗

Antiangiogenic and antiproliferative activity of suramin analogues.

The purpose of this study was to test the ability of 70 polyanionic analogues of suramin to inhibit angiogenesis. The ID50, the dose that produced 50% inhibition of angiogenesis, was determined for suramin and each of the analogues by measuring the ability of various amounts to inhibit angiogenesis in vivo in the chick egg chorioallantoic membrane (CAM) assay. Of the 70 analogues, 11 had antiangiogenic activities similar to suramin and an additional 7 were significantly more potent than suramin. All seven of these analogues were from the naphthalenetrisulfonic acid group and contained large urea groups. The benzene sulfonic and disulfonic acid analogues were less active inhibitors of angiogenesis than the naphthalenetrisulfonic acid analogues. Replacement of the naphthalenetrisulfonic acid groups by aliphatic carboxylic acids or benzoic acid gave analogues with very little antiangiogenic activity. In subsequent experiments, the antiproliferative activity of selected analogues on basic FGF (bFGF)-stimulated growth of immortalized human microvascular endothelial cells in vitro was determined. Analogues that inhibited angiogenesis to a greater extent than suramin in the CAM assay generally showed a greater antiproliferative effect on bFGF-induced growth of human microvascular endothelial cells. These results suggest that some of the polyanionic analogues may be potent therapeutic agents for cancers and angiogenesis-dependent diseases.

Animals↗

Thermal denaturation and renaturation of a fermentation broth of xanthan: rheological consequences.

The rheological properties of an unpasteurised and concentrated xanthan fermentation broth (c = 30 g/l 0.02 M in salt) were studied before heat treatment and after a thermal heating/cooling cycle performed at various polymer concentration conditions (10-30 g/l). At concentrations below 10 g/l heat denaturation occurs with dissociation of the native double-stranded structure into two single strands. At higher concentration, no complete dissociation happens. Changes in both viscoelastic properties and molecular weight are observed after heating above the melting order-disorder temperature (Tm). They are related to the order disorder conformational transition of the xanthan molecules. Xanthan renatured in concentrated conditions (above 10 g/l) has a higher viscosity than that of the native sample and displays more gel-like properties. The inhibition of the dissociation in two single strands in the high concentration range is attributed to the presence of nematic phases observed by viscoelastic measurements and apolar microdomains evidenced by the addition of a neutral detergent.

Carbohydrate Conformation↗

Associative behaviour of hydrophobically modified carboxymethylpullulan derivatives.

Hydrophobically modified carboxymethylpullulan (HMCMP) samples were obtained by reaction of small amounts of C16 alkylamine on carboxylic groups of the corresponding polyacid. The molar contents of alkyl chains ranged from 1.3 to 6.8% with respect to the anhydroglucose units (AGU) and the degree of substitution (DS) of carboxylic groups varied from 0.76 to 0.84. Solution properties of the sodium salt of HMCMPs were studied mainly by viscometric and size-exclusion chromatography/light-scattering methods. The low-shear viscosity of modified pullulans in 0.1 M NaCl solutions drastically increases with the hydrophobic content and polymer concentrations and the 6.8% modified sample has a quite pseudoplastic behaviour. These data showed that the polymers aggregated intermolecularly and displayed a compact globular structure in dilute solution. Furthermore, addition of NaCl or ethanol induced a decrease in viscosity although the molecular weights remained approximately constant. These results are consistent with a collapse of the polysaccharide aggregates.

Amines↗

[Flecaine: drug of choice for supraventricular tachycardias with anasarca. A case report].

We report a case of fetal supraventricular tachycardia with intra uterine cardiac failure, treated with oral administration of flecainide acetate (Flecaine) to the mother. This treatment was rapidly effective. The fetus converted to sinus rythm in 5 days and the ascites had completely resolved in 10 days. We believe that flecainide acetate can be used as the "first line agent" for fetal supraventricular tachycardias with cardiac failure.

Anti-Arrhythmia Agents↗

[Fetal supraventricular tachycardia with anasarca complicating benign extrasystole: treatment with flecainide. Apropos of a case].

We report a case of fetal supraventricular tachycardia with intra-uterine cardiac failure, who complicate benign premature beats. It was treated with oral administration of flecainide acetate (Flecaine) to the mother. This treatment was rapidly effective. The fetus converted to sinus rhythm in 5 days and the ascites had completely resolved in 10 days. We conclude, that fetus with premature beats must be observed every 15 days, and we believe that flecainide acetate can be used as the "first line agent" to the fetal supraventricular tachycardias with cardiac failure.

Anti-Arrhythmia Agents↗

[The venous valve: non-invasive imaging of its functioning].

B Mode and TM mode Imaging are useful tools to illustrate directly the venous valve motion. Using B Mode, venous valve are echogenic with a particular kinetic as regards its topography. So it's possible to determine in TM Mode a "pseudo-cardiac" valvular motion (jugular vein) and a "pseudo-diaphragmatic" motion for the lower limbs veins. Valvular motion assures unidirectional venous flow.

Humans↗

Evaluation of virological procedures to detect fetal human cytomegalovirus infection: avidity of IgG antibodies, virus detection in amniotic fluid and maternal serum.

Human cytomegalovirus (HCMV) is the most common cause of viral intrauterine infection and fetal damage largely due to maternal primary infection. Virological procedures which are able to detect HCMV fetal infection were evaluated. HCMV IgG antibodies were detected in 62.5% of the pregnant women and 1.47% had a primary infection. From March, 1992 to August, 1995, 29 seroconversions were observed, and in 64 other cases. HCMV IgM antibodies were detected in the first serological test. The mean IgG antibody avidity test (AI) was 31% for the 11 seroconversions tested and 74% in 32 cases where IgG and IgM HCMV antibodies were detected in the first serum. In the 29 HCMV seroconversions, 19 amniocentesis were carried out and 12 fetuses (41.4%) were infected in utero. In four amniotic fluids positive in culture and PCR, the fetus or newborns were infected and in one out of the two cordocentesis undertaken, hepatitis, anemia, and thrombocytopenia were noted. In four other cases, investigations seeking HCMV in amniotic fluid were negative whereas infants were infected at birth. Among the 64 cases with positive HCMV IgM and IgG antibodies detected in the first serological test, three fetuses were infected in utero, but no amniotic fluid was available in these cases. Amniotic fluids were studied in 39 cases, and HCMV detection by culture and PCR-hybridization was negative. HCMV DNA was detected in the maternal sera of five out of 21 pairs of seroconversions and in two cases on the first negative serum. The assay was also carried out on 50 of the 64 HCMV IgM positive sera. Two had detectable HCMV DNA.

Amniotic Fluid↗

[Tumor cell dissemination in bone marrow and peritoneal cavity. An immunocytochemical study of patients with stomach or colorectal carcinoma].

The tumor spread and the radicality of surgical resection are the most important facts in a patient's prognosis. In spite of curative tumor resection many patients die from metastases or local tumor recurrence. One possible reason is early dissemination of tumor cells which cannot be detected with clinical methods of examination. For this reason the aim of our study was to examine both bone marrow and peritoneal lavage for disseminated tumor cells with an immunocytochemical technique in patients with a gastrointestinal carcinoma. We also wanted to find out whether there was any correlation between the incidence of tumor cell detection and the TNM classification, staging and tumor grading and whether disseminated tumor cells have any prognostic significance. Our study included 54 patients who underwent surgery in our clinic for a carcinoma of the stomach (20 patients) or the colorectum (34 patients) from November 1993 to December 1994. At the beginning of the operation bone marrow had been taken from the iliac spine, and the abdomen was irrigated with 1000 ml saline solution immediately after laparotomy or laparoscopy. After cell separation with Ficoll density centrifugation 5 x 10(5) cells were applied per slide by a cytospin technique. For detection of the tumor cells we used the APAAP technique and the following monoclonal antibodies: KL1, CK2, anti-CEA, 17-1A (bone marrow) and Ber-EP4, B72.3, anti-CEA and 17-1A (peritoneal lavage). Altogether 77% of all patients had tumor cells in the bone marrow and 69% in peritoneal lavage fluid. It was possible to detect tumor cells in bone marrow (67%) and peritoneal lavage fluid (25%) even of patients with T1 tumors. The percentage increased with depth of wall infiltration. There was a marked difference in bone marrow aspirates between patients with lymph-node-negative tumors (N0) and those with lymph-node-positive tumors (N+): 65% had tumor cells in N0 and 85% in N+ stages. This trend was also seen in patients with (M1) and without (M0) metastases, in both bone marrow aspirates and peritoneal lavage fluid. In bone marrow there was a good correlation of tumor cells with staging, but in peritoneal lavage fluid this was not so. Finally, we detected tumor cells more often in bone marrow and peritoneal lavage fluid of patients with poorly differentiated tumors (G3) or diffuse Lauren type than in patients with moderately differentiated tumors (G2) or intestinal Lauren type. After a median follow-up period of 12.5 months patients with disseminated tumor cells had a lower survival rate than patients without tumor cells.

Adult↗

5-HT2 receptors are partially involved in the relationship between renin release and delta relative power.

A strong relationship was previously described between the nocturnal oscillations of plasma renin activity (PRA) and the sleep cycles, with levels of PRA that increase during non rapid eye movement sleep and decrease during rapid eye movement sleep. This study was designed to determine whether ritanserin, a 5-hydroxytryptamine-2 (5-HT2) receptor antagonist known to increase slow wave sleep both in human and in animals and to decrease plasma renin activity response to serotonergic stimulation in the rat, would uncouple this relationship. Eight subjects underwent two randomized night studies after having received either placebo or 5 mg ritanserin administered in the morning. They were subjected to 8 hour polysomnography, including spectral analysis of the electroencephalogram and to continuous blood sampling. Blood was sampled from 2300 to 700h every 10 min and plasma renin activity (PRA) was measured by radioimmunoassay of angiotensin 1. The nocturnal profiles were analysed using the pulse detection program ULTRA. Ritanserin produced the expected increase in slow wave sleep (SWS) duration (132 +/- 10 min under ritanserin vs 72 +/- 9 min under placebo; p < 0.001) and a significant increase in delta relative power (69 +/- 2% under ritanserin vs 60 +/- 2% under placebo; p < 0.01). The mean overnight PRA levels had a tendency to decrease under ritanserin (1.66 +/- 0.34 ngAngl/ml per h under ritanserin vs 1.48 +/- 0.31 ngAngl/ml per h under placebo; p = 0.08). Individual PRA oscillations were preserved and remained strongly associated with delta power oscillations. PRA peak levels were similar in both experimental conditions, but the absolute amplitude of the oscillations was decreased under ritanserin (1.50 +/- 0.36 ngAngl/ml per h vs 1.04 +/- 0.14 ngAngl/ml per h; p < 0.05). These results demonstrate that ritanserin, at a dose that augments delta power, only weakly affects renin release, which suggests that 5-HT2 receptors are only partially involved in the processes coupling renin release and SWS and that other mechanisms probably control the sleep-associated variations in PRA.

Adult↗

Slow wave electroencephalic activity parallels renin oscillations during sleep in humans.

Previous studies have demonstrated that the nocturnal oscillations of plasma renin activity (PRA) exactly reflect rapid eye movement (REM) non-REM (NREM) sleep alternation with levels of PRA that increase during NREM sleep and decrease during REM sleep. These studies were based exclusively on conventional scoring of sleep stages. In the present study, we used spectral analysis of the sleep EEG to determine the variations in the different EEG frequency bands, together with PRA profiles. Eight male volunteers participated in a 1 night study. They were subjected to 8 h polysomnography including spectral analysis of the EEG, and to blood sampling every 10 min. Delta relative power and Sleep Intensity Index and PRA oscillations ran parallel in all individuals. An increase in slow waves was associated with an increase in PRA, whereas a decrease was associated with a decrease in PRA. Cross-correlation coefficients were significant and ranged between 0.34 and 0.74. Conversely, theta, alpha and beta bands and the EEG mean frequency were inversely proportional to PRA, with lower cross-correlation coefficients. These results may give further support to the hypothesis of a common mechanism controlling both SWA and renin release from the kidney.

Adult↗

Assessment of plant tissue feeding by sand flies (Diptera: Psychodidae) and mosquitoes (Diptera: Culicidae).

Plant tissue feeding by Culex pipiens molestus (Forskål) was determined by identification of plant residues, differentially stained with Calcofluor, in dissected mosquito guts. Such residues were found in 42.3% of 286 field-caught mosquitoes. A method for determination of plant tissue feeding from specific sources is described. Before feeding branches were suffused with Calcofluor stain which binds to plant cell walls; stained residues of this tissue in the insect gut are indicative of feeding. Laboratory experiments with Phlebotomus papatasi (Scopoli) and C. p. molestus verified that feeding on labeled and untreated branches was similar. These experiments quantified the frequency of feeding by sand flies on 15 plant species and by the mosquitoes on 6 plant species. Labeled branches of plants that were fed upon frequently in the laboratory were used as baits in field tests. In the laboratory, the percentage of P. papatasi feeding on Prosopis farcta (Macbride) was 75.8% and on Ricinus communis (L.) 67.2%, whereas 29.4 and 17.9% of the sand flies caught in the field near labeled plants were marked, respectively. Similarly, 84.8% of the C. p. molestus fed on Ochradenus baccatus (Delile) in the laboratory and 11.0% of the mosquitoes caught near labeled baits were marked. These experiments show that plant tissue is common in the diet of C. p. molestus in the Jordan Valley, and that the plants tested in the field are natural sources of this diet for either sand flies or mosquitoes.

Animals↗

In vitro and in vivo comparative studies on chelation of aluminum by some polyaminocarboxylic acids.

Since desferrioxamine exhibits toxic effects, the possible use of several other therapeutic agents in acute aluminum intoxication has been investigated in this study. The potential for the chelation of aluminum (Al) by different compounds has been first determined using two in vitro techniques. The formation of stable complexes with Al in an aqueous solution has been evaluated by using pulse polarography. This technique allows the influence of temperature and of calcium (Ca) to be studied for each compound. Certain compounds (HEDTA, DTPA) showed extensive chelation in the presence of Ca2+ at a temperature of 37 +/- 1 degree C. An ultrafiltration technique combined with Al determination by atomic emission spectroscopy (A.E.S.) has allowed the ability of different substances to complex Al that was previously bound to serum proteins, to be estimated. The kinetics of chelation and the minimum efficient concentration have been determined for all of the products studied. The real efficacies of the compounds were studied by in vivo investigations to compare the effectiveness of the best chelating agents (DFO, HEDTA and EDTA) on the distribution and excretion of Al, after repeated i.p. administration to rats. HEDTA shows a chelation potential as widely active as the DFO potential.

Acetates↗

In vitro and in vivo evaluation of potential aluminum chelators.

The potential for aluminium (Al) chelation by different compounds was determined using 2 in vitro techniques. The formation of stable complexes with Al in an aqueous solution was evaluated using pulse polarography. This technique allowed the influence of temperature and calcium (Ca) to be studied for each compound. Certain compounds (EDDHA, HAES, citric acid and HBED) showed great chelation in the absence of Ca2+ at a temperature of 37 +/- 1 C. An ultrafiltration technique combined with Al determination by atomic emission spectroscopy allowed the efficiency of different substances to complex Al that were previously bound to serum proteins to be estimated. The kinetics of chelation and minimum efficient concentration have been determined for all products studied. EDDHA had chelation potential similar to DFO. The real efficacies of the compounds were studied in vivo to compare the effectiveness of repeated administrations of the best chelating agents (EDDHA, DFO, HAES and tartaric acid) on the distribution and excretion of Al after repeated i.p. administrations to rats. Intraperitoneal EDDHA significantly increased urinary metal (Al, Ca, Cu, Fe and Zn) excretion. These excretions may be correlated to a renal toxic potential property.

Aluminum↗

Cyclic RGD peptides ameliorate ischemic acute renal failure in rats.

Renal tubular obstruction is an important contributor to the pathophysiology of acute renal failure. Based on the previous findings of the role played by arginine-glycine-aspartic acid (RGD) recognizing integrins in tubular obstruction, this study examined the effect of RGD peptides on the course of ischemic acute renal failure in rats. For in vivo studies, animals were subjected to 45 minutes of unilateral renal ischemia with contralateral nephrectomy, and cyclic RGD peptides or a linear biotinylated RGD peptide were injected systemically after the release of renal artery clamp. In vitro studies compared the potency of the peptides in inhibiting BS-C-1 cell-matrix and cell-cell adhesion. Two novel cyclic RGD peptides utilized in these studies showed different inhibitory potency in preventing cell-matrix adhesion: cyclic RGDDFV was a highly potent in vitro inhibitor of BS-C-1 cell-matrix adhesion, whereas cyclic RGDDFLG was less potent. In cell-cell adhesion assays, however, both peptides were equipotent. Despite the differences in inhibiting cell-matrix adhesion, a single systemic administration of either peptide improved creatinine clearance postoperatively and accelerated recovery of renal function with a rank order: cyclic RGDDFV > or = RGDDFLG >> RDADFV (inactive control). These findings represent the first in vivo demonstration of the effectiveness of cyclic RGD peptides in ameliorating ischemic acute renal failure, and suggest that in this setting RGD peptides predominantly inhibit cell-cell adhesion, whereas inhibition of cell-matrix adhesion is of lesser significance.

Acute Kidney Injury↗