[Hypo- and hyperkalemias: causes, symptoms, treatment].
Explore the source record for details and available documents.
Humans↗
Biomedical subjects
H Simon
Publications and source records attributed to H Simon.
[Clinical significance of histologic mastopathy diagnosis using quantitative procedures].
Examinations were applied to 101 patients with simple fibrocystic mastopathy (15 cases), proliferative mastopathy (52 cases), invasive ductal carcinoma in concomitance with mastopathy (21 cases), and normal mammary glands (13 probands) in a prospective clinico-morphological pilot study. The use of Robotron A 6471/AMBA-R, a system for automated microscopic image analysis, together with improved methods, has opened up new possibilities for early detection of precancerous changes of the mammary gland. Significant differences were identified between the two clinically relevant groups, II and III, of proliferative mastopathy by quantitative analysis of ductal epithelial proliferations through reproducible measuring data were obtained together with highly distinctive karyometric and histometric parameters. Multiparametrical analysis also provided suggestions to the effect that cases of proliferative mastopathy III, probably, break down into two groups with presumedly differentiated carcinoma risks. Hence, it may well be possible that the biological importance of atypical ductal epithelial proliferations differs from case to case.
Adult↗
[Grading of urinary bladder tumors by automated microscopic image analysis].
Studies were undertaken on biopsies from urinary bladder papillomas and urothelial carcinomas of different grades (G1-G3) along with normal urinary bladder mucosa from a total of 145 patients. They were performed by use of automated microscopic image analysis (system Robotron A 6471; software AMBA/R) and resulted in making objective the tumor grading and lead to the detection of both papillomas and G1-carcinomas with high proliferating activity. In addition, we were able to separate the G2-carcinomas into two groups which probably show different biological behaviour. They cannot be discriminated by conventional morphological methods but their existence is consistent with clinical observations.
Aged↗
A novel long-lasting dopamine receptor blocker: haloperidol-bovine serum albumin conjugate.
The present study was undertaken in order to develop a long-lasting antagonist of dopamine receptors with a technique applicable to other molecules. Haloperidol was immobilized on a macromolecular backbone (bovine serum albumin) with a coupling ratio of 14 molecules haloperidol per molecule of bovine serum albumin. The long-lasting blockade of dopamine receptor activity was evaluated with the d-amphetamine-induced rotation model in rats. Unilateral intracerebral infusion of the conjugate into the caudate nucleus induced a blockade of dopamine receptors which lasted more than six days. The conjugate was able to trigger a greater amphetamine-induced rotation rate then haloperidol alone. This ipsilateral rotation appeared after doses of conjugate lower than those needed for unilateral haloperidol intracaudate infusion. This compound will enable the reversible blockade of dopaminergic transmission in a restricted area of the brain (diffusion of the conjugate was studied in detail) over a period of time needed for a behavioural study without the drawbacks of chemical or mechanical lesions.
Animals↗
Modulation of dopaminergic activity in the nucleus accumbens following facilitation or blockade of the dopaminergic transmission in the amygdala: a study by in vivo differential pulse voltammetry.
Using in vivo voltammetry, dopaminergic (DAergic) activity in the nucleus accumbens (ACC) was assessed following microinjection of DAergic agonists and antagonists in the amygdala (AMY). It was found that DAergic activity in the ACC was under the inhibitory influence of DAergic transmission in the AMY. Therefore, it can be suggested that there is a functional interdependence between the activity of these two DAergic pathways originating from the ventral mesencephalic region.
Amygdala↗
Behavioral study after local injection of 6-hydroxydopamine into the nucleus accumbens in the rat.
Anatomically, the nucleus accumbens (n.Acc.) has been considered as an interface between limbic and striatal sensorimotor structures. In the light of this hypothesis we have investigated the behavioral effects of destruction of the dopaminergic innervation of the n.Acc. after local injection of 6-hydroxydopamine. The following behavioral deficits were observed: hypoexploration in a 4-hole box and 2-compartment field, failure to inhibit response strategies either with positive reinforcement in a straight alley test or negative reinforcement in a passive avoidance test. These disturbances comprise a syndrome of perseveration, reduced distraction by irrelevant information, decreased behavioral switching and flexibility, and a paradoxical locomotor disinhibition in an emotional context. Very similar behavioral changes are found following lesions of limbic structures. In addition, these lesioned animals exhibit an enhanced latency to initiate motor responses. This deficit of behavioral initiation is classically observed in motor striatal disease. It is suggested that the n.Acc. is a key structure for the integration of limbic and striatal sensorimotor functions.
Animals↗
Profound disturbances of spontaneous and learned behaviors following lesions of the nucleus basalis magnocellularis in the rat.
It has been shown that a marked decline in the cortical activity of the cholinergic synthesizing enzyme choline-acetyltransferase (ChAT), accompanied by a severe neuronal loss in the nucleus basalis magnocellularis of Meynert occurs in the brains of patients with senile dementia of the Alzheimer type. However, the functional role of these neurons is largely unknown. In fact, very few studies have been done in animals. In this paper we report the behavioral effects of the lesion of the nucleus basalis magnocellularis in the rat either by radiofrequency current or by ibotenic acid injection at the level of the cell bodies. The two kinds of lesion lead to a profound disturbance of spontaneous and learned behaviors. There is a complete disorganization of behavior which is evidenced by an enhanced locomotor activity, an alteration in alimentary and hoarding behavior. In addition, we observed a deterioration of spatial memory and an incapacity to reverse a previously learned response. Biochemical assay showed that radiofrequency and ibotenic acid lesions produced a decrease of ChAT activity in the prefrontal and sensorimotor cortices and in amygdala without affecting the hippocampus or striatum. Ibotenic acid lesions seem to specifically destroy the cell bodies of the nucleus basalis magnocellularis since the dopaminergic and noradrenergic fibers of passage remained intact as measured by the unchanged level of endogenous catecholamine concentration in the terminal region in the prefrontal cortex. Presently, it cannot be said that the behavioral syndrome results solely from the lesion of the cholinergic neurons. Also, it is likely that the lesion of the nucleus basalis magnocellularis in the rat does not exactly reproduce the behavioral syndrome observed in Alzheimer's disease in man. However, this experimental approach in leading to a better knowledge of the functioning of these neurones could improve our understanding of this disease.
Animals↗
Effects of D- and L-amphetamine on dopamine metabolism and ascorbic acid levels in nucleus accumbens and olfactory tubercle as studied by in vivo differential pulse voltammetry.
Differential pulse voltammetry used together with electrochemically pretreated carbon fibre microelectrodes allowed us to detect in vivo two well-separated peaks in nucleus accumbens and olfactory tubercle. The two peaks situated at -50 mV (peak 1) and + 100 mV (peak 2) correspond, respectively, to the oxidation current of the ascorbic acid and to the oxidation current of the 3,4-dihydroxyphenylacetic acid (DOPAC). The experiments were carried out on anesthetized rats. Voltammograms were recorded in nucleus accumbens and olfactory tubercle every minute alternately in each structure. In control conditions, peak 1 height was greater in olfactory tubercle than in nucleus accumbens and peak 2 height was greater in nucleus accumbens than in olfactory tubercle. Both isomers of amphetamine induced a decrease of the peak 2 height in the two structures. The decrease was greater in olfactory tubercle. Higher doses of L-amphetamine were required to induce peak 2 height decrease of the same extent. Both isomers induced a marked increase of the peak 1 height in nucleus accumbens whereas peak 1 height in olfactory tubercle was slightly augmented. D-amphetamine was more effective than L-amphetamine in increasing peak 1 height.
3,4-Dihydroxyphenylacetic Acid↗
Chiral products from non-pyridine nucleotide-dependent reductases and methods for NAD(P)H regeneration.
Enoate reductase (EC 1.3.1.31) from a Clostridium tyrobutyricum strain catalyses the stereospecific reduction of many different alpha, beta-unsaturated carboxylates, aldehydes and even some ketones. The enzyme accepts electrons from NADH and, 1.5 times faster, from reduced methyl viologen (1,1'-dimethyl-4,4'-bipyridinium). Another new type of non-pyridine nucleotide-dependent reductase has an extremely broad substrate specificity for 2-oxo-carboxylates and 2-oxo-dicarboxylates. In crude extracts from Proteus mirabilis and Proteus vulgaris, specific activities of 2-12 mumol product formed per mg protein per min can be found when reduced methyl or benzyl viologen is used as electron donor. The products are (2R)-hydroxy acids. Enoate reductase and 2-oxo-carboxylate reductase are suitable for electro-enzymic reductions in which catalytic amounts of viologens are continuously reduced in an electrochemical cell. This procedure has three advantages: (1) regeneration of NAD(P)H by a second enzyme and substrate is not required, (2) the unstable pyridine nucleotides are not required in the reaction mixture, and (3) the rate of the reaction can be observed continuously by measuring an electric current. Several yeasts, as well as aerobic and anaerobic bacteria, catalyse the reduction of NAD(P)+ by reduced methyl viologen. Such cells can be used for electro-microbial reductions when only pyridine nucleotide-dependent reductases are present. Information about the enzymes which catalyse the reduction of NAD(P)+ at the expense of reduced methyl viologen is given.
Alcohol Oxidoreductases↗
Dopamine-sensitive alternation and collateral behaviour in a Y-maze: effects of d-amphetamine and haloperidol.
The degree of alternation of arm choice in a Y-maze was examined on 15-min tests over 4 days in rats treated (IP) with saline, amphetamine (0.5 or 2.0 mg/kg) or pretreated with haloperidol (0.08 mg/kg) in each condition prior to test. On day 1 amphetamine-treated animals chose arms at random, but from day 2-4 those receiving the higher dose perseverated their choice. Controls maintained alternation. These effects could be prevented by haloperidol pretreatment. Amphetamine treatment increased the frequency of rearing at the middle, choice-point of the maze more than at the end of an arm. The increase at the mid-point was suppressed by haloperidol pretreatment from day 1 and at the end of an arm from day 2. Amphetamine induced an increase in head-turning/"looking" that was suppressed by haloperidol from day 2. The effect of haloperidol in increasing the duration of an item of looking or rearing at the end of an arm also started later in testing. Two effects are postulated to have occurred: (i) a conflict on day 1 between novelty-controlled sensory or attentional effects that leads to an alternation of arm choice and amphetamine-induced dopaminergic activity that facilitates an alternation of behavioural responses. The result was random choice and increased rearing at the choice point. (ii) On days 2-4 the drug-induced effects on switching motor responses came to control behaviour.
Animals↗
The effect of 6-OHDA lesions of the lateral septum on schedule-induced polydipsia.
In this study the relationship between 6-hydroxydopamine lesions of dopaminergic innervation of the lateral septum and schedule-induced polydipsia was examined. Animals with lesions were found to have a significant increase in water intake during a test involving an intermittent schedule of food delivery. Additional experiments with these animals showed that lesions had no effect on: (i) spontaneous drinking, the amount of drinking after 24 h food or water deprivation, water intake following a hypertonic saline challenge; (ii) eating behavior with or without food deprivation; and (iii) spontaneous locomotor activity. This increase in adjunctive behavior is discussed in the light of an enhanced frustrative effect induced by the septal lesions.
Animals↗
Effect of haloperidol and sulpiride on dopamine metabolism in nucleus accumbens and olfactory tubercle: a study by in vivo voltammetry.
Differential pulse voltammetry used with electrochemically pretreated carbon fibre microelectrodes enables separation between the two peaks corresponding to the ascorbic acid and catechol oxidation currents. The effects of haloperidol and sulpiride on the 3,4-dihydroxyphenylacetic acid peak recorded in the nucleus accumbens and olfactory tubercle of rats were studied. Chloral hydrate anaesthetized preparations and chronic preparations were used. A microdevice was designed to implant electrodes in freely moving rats. Voltammograms were recorded every minute in each structure in acute preparations and every 2 min in chronic preparations. In acute preparations haloperidol induced a similar dose-dependent increase in the catechol oxidation peak in both structures. Sulpiride at all doses only induced an increase in the olfactory tubercle. In chronic preparations haloperidol and sulpiride had even larger effects on the 3,4-dihydroxyphenylacetic acid peak in both regions. In these preparations sulpiride induced a significant increase in nucleus accumbens. The effects induced by haloperidol in the two regions were greater than those induced by sulpiride. The main conclusions of this study are that the results of voltammetry agree with biochemical results on the effects of haloperidol and sulpiride on dopamine metabolism. An interaction of chloral hydrate with the effects of the two neuroleptics was also observed.
3,4-Dihydroxyphenylacetic Acid↗
Alternation behavior, spatial discrimination, and reversal disturbances following 6-hydroxydopamine lesions in the nucleus accumbens of the rat.
The effects of dopaminergic depletion of the nucleus accumbens was tested in various behavioral tasks such as alternation, spatial discrimination, and reversal learning, and in an extinction paradigm in a T maze. Animals with lesions showed impairment of spontaneous alternation behavior, disturbances in the acquisition of spatial discrimination, and great difficulty in reversing previously learned habits. In the extinction phase, experimental animals are unable to adjust their behavior, and continue to choose the previously reinforced arm of the T maze. It is suggested that the nucleus accumbens plays an important role in the transition of motivation into action, and that dopamine has a facilitatory influence on the mediation of these processes.
Animals↗
Morphology of early stages of ENU-induced brain tumors in rats.
Tumors were induced in experimental animals in order to investigate early tumor growth with conventional histology and gliofibrillary acid protein (GFAP) demonstration with the peroxidase-antiperoxidase (PAP) method. In one experiment, the animals were killed after transplacental ENU administration, when microtumors were suspected; in the second experiment, the animals were followed up to their natural death and microtumors found at random were used for analysis. Conventional histology revealed 3 types of microtumors: growth restricted to the subventricular matrix, growth in the neighbourhood of the ventricles with obvious or probable connection to the ventricular zones and small tumors observed exclusively in the white matter. The latter tumors by conventional staining were composed of small round cells, considered to be oligodendrocytes. They did not contain GFA-protein positive cells within the tumor. The tumor in presumable and visible connection with the ventricular lining did contain GFAP-positive astrocytes. In the very small subventricular tumors, the small round cells (oligodendrocytes) were in continuous contact with the identical interfascicular glial cells, while GFAP positive astrocytes seemed to stem from the subventricular astrocytes (tanycytes, ependymoglia). The ependyma itself was always preserved. A twofold origin of these experimental tumors with probable development into one common cytological glial type is assumed.
Animals↗
Enhanced frustrative nonreward effect following 6-hydroxydopamine lesions of the lateral septum in the rat.
The effect of local injections of 6-hydroxydopamine (6-OHDA) into the lateral septum was tested in a paradigm known to lead to an energizing behavior, through a possible frustrative effect, induced by partial or total omission of reward in hungry rats. Biochemical assays in the septum showed that 6-OHDA reduced endogenous dopamine and, to a lesser extent, noradrenaline concentrations and left intact noncatecholaminergic neurons such as serotoninergic terminals. The first behavioral experiment was conducted in a double straight alley. The animals were submitted to three phases of testing with differing degrees of reinforcement: (a) an acquisition phase, in which the reinforcement was continuously delivered in the goal box of the two alleys, (b) a partial reinforced phase, in which animals received 50% partial reinforcement in the first alley and continuous reinforcement in the second alley, and (c) an extinction phase performed in one alley without any reinforcement. Animals with lesions ran faster for food than controls in the partial reinforcement or extinction situation, although there was no difference between the two groups in the acquisition phase of the continuous schedule of reinforcement or in the 50% reinforced trials of the partial reinforcement phase. The two groups also behaved similarly after the first six trials of the extinction phase. In a second experiment, the animals were tested in a lever-press conditioning task. Animals with lesions and control animals learned this task equally well, both with respect to the number of lever presses and the time to obtain a fixed number of food pellets.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Structure of enoate reductase from a Clostridium tyrobutyricum (C. spec. La1).
Enoate reductase from Clostridium tyrobutyricum was purified by a rapid novel procedure. Chromatography on DEAE-Sepharose and on hydroxyapatite resulted in a high yield of about 90% pure enzyme in less than 10 h. A purity greater than 98% could be obtained by additional chromatography on Sephacryl S-300. The enzyme sediments in the analytical ultracentrifuge as a single, symmetrical boundary with a velocity of S(0)20,w = 24.9 S. Equilibrium ultracentrifugation yielded a molecular mass of 940 000 +/- 20 000 Da. The enzyme contains one type of subunit as shown by dodecyl sulfate electrophoresis and partial sequence determination. A subunit molecular mass of about 73 000 Da was established by dodecyl sulfate electrophoresis and by sedimentation equilibrium analysis in guanidine hydrochloride. In addition to FAD, iron and labile sulfur, the enzyme purified by the new method showed approximately 0.7 mol of FMN per mol of subunit. A dissociation product sedimenting at a velocity of S(0)20,w = 9.8 S can be obtained by various experimental protocols. The fragment was obtained in pure form by gel permeation chromatography. The molecular mass was 230 000 +/- 10 000 Da as shown by sedimentation equilibrium analysis. Thus it appears that the dissociation product is a trimer of the 73 000-Da subunit. The formation of the 10-S fragment by dissociation of the native enzyme is accompanied by the loss of most of the FMN, whereas the FAD content is not changed. The fragment catalysed the reduction of acetylpyridine adenine dinucleotide by NADH. However, enoate reductase activity with NADH or methylviologen as cosubstrate was low. Electron micrographs of negatively stained enoate reductase show trigonal symmetry. The data suggest that enoate reductase is a dodecamer (tetramer of trimers) with tetrahedral symmetry.
Clostridium↗
Observations on the elimination of water from 2-hydroxy acids in the metabolism of amino acids by Clostridium sporogenes.
Cell-free extracts of Clostridium sporogenes catalyse the water elimination from (2R)-phenyllactate in the presence of one of the energy-rich compounds acetyl-CoA, acetylphosphate or ATP and coenzyme A. Water is eliminated from (2R)-phenyllactoyl-CoA without any of the aforementioned additions. Cinnamoyl-CoA also acts catalytically. One molecule of cinnamoyl-CoA causes the elimination of water from more than 8 molecules phenyllactate. This is important from an energetic point of view since less than 2 mol ATP are formed per 2-3 mol metabolized amino acids. An activation of the hydroxy group of the alpha-hydroxy acid in form of a phosphate ester can also be excluded for energetic reasons.
Adenosine Triphosphate↗
Purification and some properties of an acryloyl-CoA reductase of Clostridium kluyveri.
Acryloyl-CoA reductase, a presumably previously unknown soluble enzyme, is present in Clostridium kluyveri. It catalyses the reduction of the carbon-carbon double bond of acryloyl-CoA or ethyl vinyl ketone and other alpha, beta-unsaturated carbonyl compounds at the expense of reduced methylviologen. On the basis of a Vmax/Km ratio, which is at least 18 times higher than that for the next best substrate (E)-2-butenoyl-CoA, the enzyme is called acryloyl-CoA reductase. A purity of over 90% was achieved. The apparent molecular mass, as determined by gel chromatography, is 28.4 kDa. Dodecyl sulfate gel electrophoresis shows subunits with a molecular mass of 14.2 kDa. Based on a molecular mass of 28.4 kDa about 1.5 mol FMN have been observed. Less than 0.2 g-atom iron per mol protein were determined. Ferredoxin or flavodoxin seem to be able to carry electrons from hydrogenase to the acryloyl-CoA reductase. The addition of hydrogen to the alpha-carbon of ethyl vinyl ketone occurs from the re-side.
Chromatography, DEAE-Cellulose↗