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Biomedical subjects

B Fischer

Publications and source records attributed to B Fischer.

At least 217 records · Page 12Linked to original sources

Saccadic eye movements of dyslexic and normal reading children.

Twenty-four children made saccades in five noncognitive tasks. Two standard tasks required saccades to a single target presented randomly 4 deg to the right or left of a fixation point. Three other tasks required sequential saccades from the left to the right. 75 parameters of the eye-movement data were collected for each child. On the basis of their reading, writing, and other cognitive performances, twelve children were considered dyslexic and were divided into two groups (D1 and D2). Group statistical comparisons revealed significant differences between control and dyslexic subjects. In general, in the standard tasks the dyslexic subjects had poorer fixation quality, failed more often to hit the target at once, had smaller primary saccades, and had shorter reaction times to the left as compared with the control group. The control group and group D1 dyslexics showed an asymmetrical distribution of reaction times, but in opposite directions. Group D2 dyslexics made more anticipatory and express saccades, they undershot the target more often in comparison with the control group, and almost never overshot it. In the sequential tasks group D1 subjects made fewer and larger saccades in a shorter time and group D2 subjects had shorter fixation durations than the subjects of the control group.

Child↗

Effects of persistent chlorinated hydrocarbons on fertility and embryonic development in the rabbit.

The commercial polychlorinated biphenyl (PCB) formulation Aroclor 1260 (4 mg/kg body weight), technical grade dichlorodiphenyltrichloroethane (DDT; 3 mg) and Lindane (gamma-hexachlorocyclohexane; 0.8 mg) were administered orally, either separately or in combination, to sexually mature female rabbits three times per week for 12-15 weeks. Oviductal and uterine luminal fluid, cleavage stage embryos (day 1 post coitum), blastocysts (day 6), fetuses, exocoelic fluid and placentae (day 11) were analysed, firstly for chlorinated hydrocarbon residues, and secondly for embryonic and fetal development. The doses applied were well tolerated by the treated animals. PCB and DDT accumulated in uterine secretions (day 6) but not in oviductal luminal fluid (day 1). Both chlorinated hydrocarbons were found in preimplantation blastocysts. Residues in day 11 fetuses were 16- (DDT) or 18-fold (PCB) higher than in day 6 blastocysts. Significant amounts were also detected in placental tissue and in exocoelic fluid. A specific accumulation of the highly chlorinated biphenyl congener no. 180 was noted in fetuses, placentae and exocoelic fluid. The clear accumulation of the chlorinated hydrocarbon compounds in luminal fluid and embryonic tissue is contrasted by rather weak effects on fertility. No statistically significant differences between treated animals and controls were observed for fertilization rate and pre- and post-implantation (up to day 11 post coitum) losses. However, in females exposed to PCB, a 20% higher loss of blastocysts was noticed, as compared with controls (P > 0.05). This effect was shown on day 6 of embryonic development and may be due to the embryotoxic activities of PCB.

Animals↗

Effects of persistent chlorinated hydrocarbons on reproductive tissues in female rabbits.

The female rabbit was used to study (i) accumulation of lipophilic chlorinated hydrocarbons in genital tract tissues and (ii) subsequent morphological and functional effects after long-term low-dose exposure. Polychlorinated biphenyl (PCB), 1,1-di(p-chlorophenyl)-2,2,2-trichloroethane (DDT) and gamma-hexachlorocyclohexane (gamma-HCH) (dosages: 4, 3 and 0.8 mg per kg body weight, respectively) and a combination of these three components (and dosages) were administered to sexually mature rabbits over a period of 12-15 weeks. The animals were killed shortly before and at various times after ovulation. Accumulation of chlorinated hydrocarbons was high in ovarian, oviductal and uterine tissues, in follicular fluid and clearly detectable in uterine secretions. In follicular fluid, the concentration and patterns of congeners and isomers of PCB and DDT were distinctly different from serum. DDT- and gamma-HCH-treated animals showed a significantly reduced ovulation rate (P < 0.002 and 0.05, respectively). During early pregnancy DDT decreased serum progesterone levels and changed the protein pattern of uterine secretion. Functional effects, however, were much less expressed compared with the highly significant accumulation of the persistent organochlorines in the genital tract.

Animals↗

Comparative studies on the affinities of ATP derivatives for P2x-purinoceptors in rat urinary bladder.

1. Radioligand binding assays have been used to determine the affinities of a series of ATP derivatives with modifications of the polyphosphate chain, adenine and ribose moieties of the ATP molecule for [H]-alpha,beta-methylene ATP ([3H]-alpha,beta-MeATP) binding sites in rat urinary bladder. 2. The replacement of the bridging oxygen in the triphosphate chain of ATP (pIC50 = 5.58) with a methylene or imido group markedly increased the affinity (691 fold in IC50 values for beta,gamma-imidoATP, 15 fold for beta,gamma-methylene ATP), and the replacement of an ionized oxygen on the gamma-phosphate with a sulphur (ATP gamma S) also led to increased affinity (5623 fold in IC50 values). 3. Modifications at N6, N1, and C-8 positions on the purine base usually reduced the affinity of ATP (a decrease of 2.8 fold in IC50 values for N6-methylATP and 8.9 fold for 8-bromo ATP), while the attachment of an alkylthio group to the C-2 position greatly increased the affinity for P2x-purinoceptors (from 3.5 to 98 fold increase in IC50 values). 4. Replacement of the 3'-hydroxyl group on the ribose with substituted amino or acylamino groups produced more potent P2x-purinoceptor agonists (an increase of 447 fold in IC50 values for 3'-deoxy-3'-benzylamino ATP and 28 fold for 3'-deoxy-3'-(4-hydroxyphenylpropionyl)amino ATP. 5. Diadenosine polyphosphates (Ap[n]A) were also shown to displace the [3H]-alpha,beta-MeATP binding. The rank order of potency was Ap6A > Ap5A > Ap4A >> Ap3A >> Ap2A. 6. Suramin, PPADS, and reactive blue 2 could competitively displace the binding of [3H]-alpha,beta-MeATP toP2X-purinoceptors, with pIC50 values of 6.26, 5.35, and 6.22, respectively.

Adenosine Triphosphate↗

Successful catheter ablation of atrial fibrillation.

INTRODUCTION: Catheter ablation of a case of incessant atrial fibrillation was attempted using linear right atrial lesions created by sequential applications of radiofrequency energy. METHODS AND RESULTS: A 46-year-old patient had incessant episodes of atrial fibrillation. He had previously undergone successful radiofrequency catheter ablation of a common atrial flutter. Antiarrhythmic drugs including amiodarone and various drug combinations were ineffective. A 7-French specially designed 14-polar catheter with interelectrode distance of 3 mm was used to create linear lesions in the right atrium. Each electrode was 4 mm in length and able to transmit radiofrequency energy. Three linear lesions, two longitudinal and one transverse that connected the two longitudinal lesions, were created using 30 radiofrequency applications of 10 to 40 W. The final application interrupted an atrial fibrillation that had been persistent for 55 minutes. No sustained atrial fibrillation was inducible despite repeated pacing maneuvers. There was no complication. In short-term follow-up of 3 months, the patient has been free of arrhythmias without antiarrhythmic medication. CONCLUSION: Successful catheter ablation of human atrial fibrillation is feasible using linear atrial lesions created by radiofrequency energy delivery. Further studies are mandatory to ascertain the efficacy and safety of this procedure, as well as to assess different catheter techniques.

Atrial Fibrillation↗

Radiofrequency catheter ablation in unusual mechanisms of atrial fibrillation: report of three cases.

INTRODUCTION: The purpose of this study was to test the feasibility of radiofrequency (RF) catheter ablation of localized mechanisms of atrial fibrillation (AF). METHODS AND RESULTS: Three patients underwent RF catheter ablation for drug-resistant atrial arrhythmias. The first two patients had either incessant atrial tachycardia or AF. In the first patient, the ECG pattern of AF was mimicked by a very rapid atrial focus, whereas in the second patient, AF was due to true degeneration of the atrial activity triggered by atrial tachycardia. In both patients, the ablation of atrial focus led to the clinical disappearance of AF. The third patient had frequent episodes of AF, which lasted several days or weeks, and two documented episodes of atrial flutter. Mapping during AF showed an irregular atrial rhythm in the atrial septum, particularly in the region surrounding the coronary sinus, whereas the entire lateral right atrial free wall exhibited a constantly organized rhythm. RF energy was applied between the tricuspid ring and both the inferior vena cava and the coronary sinus, resulting in inability to reinduce atrial flutter or sustained AF. A 6-month follow-up in this patient showed the disappearance of prolonged episodes of AF. CONCLUSION: The observations indicate that AF may be linked to "focal" mechanisms that can be treated by RF catheter ablation.

Adult↗

Interactions of oxygen radicals with airway epithelium.

Reactive oxygen species (ROS) have been implicated in the pathogenesis of numerous disease processes. Epithelial cells lining the respiratory airways are uniquely vulnerable regarding potential for oxidative damage due to their potential for exposure to both endogenous (e.g., mitochondrial respiration, phagocytic respiratory burst, cellular oxidases) and exogenous (e.g., air pollutants, xenobiotics, catalase negative organisms) oxidants. Airway epithelial cells use several nonenzymatic and enzymatic antioxidant mechanisms to protect against oxidative insult. Nonenzymatic defenses include certain vitamins and low molecular weight compounds such as thiols. The enzymes superoxide dismutase, catalase, and glutatione peroxidase are major sources of antioxidant protection. Other materials associated with airway epithelium such as mucus, epithelial lining fluid, and even the basement membrane/extracellular matrix may have protective actions as well. When the normal balance between oxidants and antioxidants is upset, oxidant stress ensues and subsequent epithelial cell alterations or damage may be a critical component in the pathogenesis of several respiratory diseases. Oxidant stress may profoundly alter lung physiology including pulmonary function (e.g., forced expiratory volumes, flow rates, and maximal inspiratory capacity), mucociliary activity, and airway reactivity. ROS may induce airway inflammation; the inflammatory process may serve as an additional source of ROS in airways and provoke the pathophysiologic responses described. On a more fundamental level, cellular mechanisms in the pathogenesis of ROS may involve activation of intracellular signaling enzymes including phospholipases and protein kinases stimulating the release of inflammatory lipids and cytokines. Respiratory epithelium may be intimately involved in defense against, and pathophysiologic changes invoked by, ROS.

Animals↗

Life-threatening pulmonary embolism with right-sided heart thrombus. Rapid recovery with recombinant tissue plasminogen activator.

We report the case of a woman treated with urokinase for acute pulmonary embolism with a right-sided heart thrombus. She developed life-threatening acute cor pulmonale which dramatically improved within 4 h with recombinant tissue plasminogen activator (rtPA). We emphasize the clinical interest of rtPA for the treatment of life-threatening pulmonary embolism.

Acute Disease↗

[Ablation of the accessory pathways by radiofrequency currents].

The introduction of ablative methods has revolutionised therapeutic strategy in cardiac arrhythmias. Accessory pathways are the most commonly targeted arrhythmogenic substrate. Several parameter may be used to determine the optimal site of ablation: accessory pathway potential, atrioventricular interval, atrial or ventricular pole of the pathway, morphology of the unipolar wave. The localisation of the accessory pathway sometimes requires specific techniques. The success rate reported in the literature is generally over 90%. However, the number of applications of radiofrequency current varies according to the authors from an average of three to eight. A combination of "timing related" criteria and direction of activation and the use of infraliminal stimuli minimise the number of radiofrequency applications. The incidence of complications in multicenter registers is 5% and the relapse rate is 8%. The long-term effects of catheter ablation are unknown, especially when used in childhood. A certain reserve should be maintained in the indications of ablation. Only high-risk, life-threatening arrhythmias, or those resistant to pharmacological intervention, are formal indications. Other (so-called "convenience") indications depend on the express wish of patients clearly informed of the advantages and risks of this method.

Arrhythmias, Cardiac↗

[Computerized tomography of bronchial arteries before and after embolization].

The whole mediastinal course of dilated bronchial arteries can be reliably visualised by spiral CT, as shown by angiography and embolisation. Based on volume acquisition in a breathhold discontinuity artifacts are avoided, thin overlapping sections are reconstructed, and a three-dimensional display of the bronchial arteries is performed. The therapeutic success of bronchial artery embolisation in a patient suffering from a tuberculous destroyed lung and hemoptysis was documented by spiral CT.

Adult↗

Identification of potent, selective P2Y-purinoceptor agonists: structure-activity relationships for 2-thioether derivatives of adenosine 5'-triphosphate.

Study of P2-purinoceptor subtypes has been difficult due to the lack of potent and selective ligands. With the goal of developing high affinity P2-purinoceptor-selective agonist, we have synthesized a series of analogues of adenine nucleotides modified on the purine ring as chain-extended 2-thioethers or as N6-methyl-substituted compounds. Chemical functionality incorporated in the thioether moiety included cyanoalkyl, nitroaromatic, amino, thiol, cycloalkyl, n-alkyl, and olefinic groups. Apparent affinity of the compounds for P2Y-purinoceptors was established by measurement of P2Y-purinoceptor-promoted phospholipase C activity in turkey erythrocyte membranes and relaxation of carbachol-contracted smooth muscle in three different preparations (guinea pig taenia coli, rabbit aorta, and rabbit mesenteric artery). Activity at P2X-purinoceptors was established by measurement of contraction of rabbit saphenous artery and of the guinea pig vas deferens and urinary bladder. All 11 of the 2-thioethers of ATP stimulated the production of inositol phosphates with K0.5 values of 1.5-770 nM, with an (aminophenyl)ethyl derivative being most potent. Two adenosine diphosphate analogues were equipotent to the corresponding ATP analogues. Adenosine monophosphate analogues were full agonists, although generally 4 orders of magnitude less potent. ATP 2-thioethers displayed pD2 values in the range of 6-8 in smooth muscle assay systems for activity at P2Y-receptors. There was a significant correlation for the 2-thioether compounds between the pK0.5 values for inositol phosphate production and the pD2 values for relaxation mediated via the P2Y-purinoceptors in the guinea pig taenia coli, but not for the vascular P2Y-receptors or for the P2X-receptors. At P2X-receptors, no activity was observed in the rabbit saphenous artery, but variable degrees of activity were observed in the guinea pig vas deferens and bladder depending on distal substituents of the thioether moiety. N6-Methyl-ATP was inactive at P2X-receptors, and approximately equipotent to ATP at taenia coil P2Y-receptors. This suggested that hybrid N6-methyl and 2-thioether ATP derivatives might be potent and selective for certain P2Y-receptors, as was shown for one such derivative, N6-methyl-2-(5-hexenylthio)-ATP.

Adenine Nucleotides↗

[Attacks of junctional tachycardia: from arrest of crisis to radical cure].

Junctional tachycardias are among the most frequent or paroxysmal supraventricular tachycardias. They are due to a reentry mechanism and include the so-called nodal reentrant tachycardias as well as tachycardias which imply a patent or hidden accessory pathway. The prognosis of these tachycardias is usually benign, but it can be made unfavourable by repeated attacks or by the presence of an accessory pathway with short anterograde refractory period which exposes the patient to severe arrhythmia. Clinicians are now provided with a therapeutic armentarium that enables them to reduce easily any attack of junctional tachycardia, but also to prevent recurrences. The intracavitary ablation technique by application of radiofrequency currents ensures the radical cure of recurrent or threatening arrhythmias by suppressing the indispensable anatomical substrate of tachycardias.

Humans↗

Structure-activity relationships of 8-styrylxanthines as A2-selective adenosine antagonists.

A series of substituted 8-styryl derivatives of 1,3,7-alkylxanthines was synthesized as potential A2-selective adenosine receptor antagonists, and the potency at rat brain A1- and A2-receptors was studied in radioligand binding experiments. At the xanthine 7-position, only small hydrophobic substituents were tolerated in receptor binding. 7-Methyl analogues were roughly 1 order of magnitude more selective for A2 versus A1 receptors than the corresponding 7-H analogues. 1,3-Dimethylxanthine derivatives tended to be more selective for A2-receptors than the corresponding 1,3-diallyl, diethyl, or dipropyl derivatives. Substitutions of the phenyl ring at the 3-(monosubstituted) and 3,5-(disubstituted) positions were favored. 1,3, 7-Trimethyl-8-(3-chlorostyryl)xanthine was a moderately potent (Ki vs [3H]CGS 21680 was 54 nM) and highly A2-selective (520-fold) adenosine antagonist. 1,3,7-Trimethyl-8-[(3-carboxy-1-oxopropyl)amino] styryl]xanthine was highly A2-selective (250-fold) and of enhanced water solubility (max 19 mM). 1,3-Dipropyl-7-methyl-8-(3,5-dimethoxystyryl) xanthine was a potent (Ki = 24 nM) and very A2-selective (110-fold) adenosine antagonist.

Adenosine↗

Tissue-type plasminogen activator mutants imitating urokinase in the peptide link between kringle and protease domains and at selected sites within the protease domain.

Tissue-type plasminogen activator (tPA) mutants which, at selected amino acid positions, mimic urokinase-type plasminogen activator (uPA) were expressed in Chinese hamster ovary cells and examined for their catalytic properties. In one series of mutants, the dipeptide Ser262 Thr263 between kringle 2 and the protease domain of tPA was (a) replaced by an Ala residue, (b) lengthened by additional Ser and Ala residues, (c) exchanged for the 16-amino-acid link between kringle and protease domains of uPA and an additional Ala residue. The activities of the latter two mutants toward plasminogen were, in the absence of fibrin, 3-5-fold higher and, in the presence of fibrin, comparable to or lower than the activity of tPA. The kinetic data suggest a short interdomain peptide in tPA as most favorable for high fibrin stimulation of tPA activity. In a second series of mutant, selected amino acid residues of the tPA protease domain were replaced by residues of the homologous uPA domain. Positions chosen for exchange are either close to the active site or are part of a tPA-specific insertion in the variable region preceding the active-site Ser residue. Compared to authentic tPA, protease-domain mutants exhibited 7.3-424-fold lower activities toward plasminogen, mainly due to lower kcat values. Km values differed only moderately. A mutant containing an additional hydroxyl group at the S1 site, tPA A473S, had lost the preference of tPA for Arg over Lys as the P1 residue in peptide substrates.

Amino Acid Sequence↗

High frequency of DNA ploidy abnormalities in preimplantation embryos of the rabbit.

The DNA ploidy of Feulgen-stained cell nuclei of in vivo preimplantation rabbit embryos was assayed by cytophotometry. DNA ploidy abnormalities were detected in single-cell nuclei readings by the criterion of > or = 5C DNA. These hypermodal DNA contents are referred as to DNA aneuploidy. Two, 4 and 6 days old rabbit embryos, all of normal gross morphology, were investigated. The incidence of embryos with DNA ploidy abnormalities increased from 17% in 2-day-old cleavage stages to 51% in 6-day-old expanded blastocysts. All these embryos were mosaics and the percentage of DNA aneuploid nuclei per embryo did not usually exceed 9%. Fifteen percent of the expanded blastocysts, however, contained up to 23% abnormal nuclei. Throughout the embryonic stages studied, the DNA content of abnormal nuclei was remarkably constant and averaged 5.8C. DNA aneuploid and euploid blastocysts did not differ in size. A maternal FSH treatment did not influence the DNA ploidy. This is the first report on the DNA ploidy pattern in preimplantation rabbit embryos. Our results indicate that DNA aneuploidy of single blastomeres is common in this species and occurs more often than generally assumed. The embryonic viability does not seem to be affected by the presence of DNA aneuploid blastomeres supporting earlier findings that a limited number of abnormal blastomeres is compatible with normal preimplantation development.

Aneuploidy↗

Renaturation of lysozyme--temperature dependence of renaturation rate, renaturation yield, and aggregation: identification of hydrophobic folding intermediates.

Renaturation of denatured-reduced hen egg white lysozyme was analyzed at temperatures between 4 and 70 degrees C using the reduced/oxidized glutathione renaturation system. With an increase in temperature to 50 degrees C both renaturation rate constant and renaturation yield increased while formation of aggregates decreased. Denatured-reduced lysozyme and early folding intermediates were less stable against heat than native lysozyme at temperatures above 60 degrees C. Renaturation at 70 degrees C resulted in no reconstitution of lysozyme activity but the highest level of aggregation. Renaturation of denatured-reduced hen egg white lysozyme was further analyzed in the presence of the hydrophobicity-indicating fluorescence dye 1-anilinonaphalene-8-sulfonate at temperatures between 10 and 40 degrees C. The change in fluorescence intensity, the generation of enzyme activity, renaturation yield, and the formation of aggregates were studied. The results showed that early folding intermediates possess a strong hydrophobic nature. With an increase in temperature both the renaturation rate and the decay rate of hydrophobicity-mediated fluorescence increased. Consequently, with increasing temperature, accumulation of hydrophobic folding intermediates and formation of insoluble aggregates decreased, leading to an increase in the renaturation yield.

Animals↗