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Biomedical subjects

J Fischer

Publications and source records attributed to J Fischer.

At least 505 records · Page 28Linked to original sources

Catalytic properties and electrostatic potential of charged immobilized enzyme derivatives. Pyruvate decarboxylase attached to cationic polystyrene beads of different charge densities.

Pyruvate decarboxylase has been covalently attached to positively charged macroporous polystyrene resins. The changes in the functional behaviour of the enzyme resulting from the electrostatic interaction of the cationic carrier polymer and the anionic substrate have been studied as function of the fixed charge concentration of the carrier. The findings confirm the connection of two widely used theoretical expressions relating electrostatic parameters with Michaelis constants.

Carboxy-Lyases↗

Synovial membrane in rheumatoid arthritis: determination of glycosaminoglycans and age-dependent correlations.

From 16 synovial membranes patients with rheumatoid arthritis morphological parameters as well as the GAG distribution pattern have been determined using 2 methods each. The results were checked by discriminant and regression analysis: The total GAG concentration of the synovialis was significantly correlated with the sum of the parameters "fibrin in organization", "granulocytes" "nad "necroses" (acute activity). A highly significant correlation between the age of patients and the severity of chronic morphological alterations (basic activity, especially proliferation) was found. The percentage of CS plus DS was positively correlated with the age of patients as well as with the basic activity of the disease, especially with the proliferation. - Contrary to this, HA was significantly decreased when related to the "chronic" parameters. No correlation could be demonstrated between the GAG components and criteria of the acute activity. The evaluating system of STIEHL and GEILER is to be preferred for obtaining morphologic-biochemical correlations. Furthermore, a diagram is proposed demonstrating the cumulative progression of rheumatoid arthritis in the synovialis as related to the GAG pattern. Its combination with morphological data (scars, proliferation, exudation) may help to describe the development of the disease more acurately.

Adolescent↗

Number of synaptic vesicles in the rat somatosensory cortex after repetitive electrical stimulation prolonging self-sustained after-discharges.

The sensorimotor area of the cerebral cortex of rats was repetitively electrically stimulated (8 Hz for sec) at 10-min intervals, inducing a gradual prolongation of self-sustained after-discharges (SSADs). At 10 min after termination of the third SSAD, the animals were perfused with a fixation solution. The homotopic area of the contralateral hemisphere was examined in the electron microscope. In the II cortical layer, the agranular synaptic vesicles in type I synapses (after Gray) were counted close to the synaptic cleft. The number of synaptic vesicles was significantly increased in the experimental animals.

Animals↗

Changes in the number, size, and shape of synaptic vesicles in an experimental, projected cortical epileptic focus in the rat.

A projected epileptic focus was induced in the brains of experimental rats by applying penicillin G sodium to the contralateral hemisphere. Synapses of type I (after Gray) in the second cortical layer of the mirror area were analyzed morphometrically in the electron microscope 30 min after application of the epileptogenic drug. The number of agranular synaptic vesicles was counted per 0.01 micron2 over the active zone of the presynaptic membrane in an area 0.1 micron wide adjacent to the active zone and in an area of the same width 0.1 micron distant from the active zone. A statistically significant increase in the number of synaptic vesicles was found in the experimental animals as compared with the controls. The number of synaptic vesicles per 0.01 micron2 area was evaluated along the inactive presynaptic membrane, both in the area adjacent to the active zone of the presynaptic membrane and in other areas at successively greater distances from the active zone. The counts in some of these latter areas were statistically significantly higher in the experimental animals. The size and shape of synaptic vesicles were evaluated in three zones, each 0.1 micron wide, parallel to the membrane of the synaptic cleft. Zone I was directly adjacent to the membrane of the synaptic cleft; zone II was 0.1 micron distant; and zone III 0.1 micron distant from the membrane. The results show that the synaptic vesicles of both the experimental and control animals are significantly smaller in zone I than in the more distant zones. This trend is more marked in the controls than in the experimental animals. Histograms of vesical areas of zones II and III in the controls point to two populations of vesicles. The volumes of vesicles are approximately 10% greater in zone I of experimental animals than in the controls. The elongation of the vesicles in the three zones does not differ statistically either in controls or in experimental animals. Experimental animals, however, have statistically more rounded vesicles than the controls. Assuming that the synpatic vesicles contain the transmitters, our results might contribute to a better understanding of the increased excitability of the epileptic focus area.

Animals↗

[Relationship between catalytic properties, fixed charge concentration and electrostatic potential of polyelectrolyte-bound enzymes].

An equation for the calculation of the electrostatic potentials of polyelectrolyte-enzyme supports from electrostatic parameters has been derived by relating two different theories which describe the catalytic behaviour of polyelectrolyte-bound enzymes. The electrostatic potentials of polyionic supports have been determined by use of experimental results, on the one hand, from the fixed charge concentration and the ionic strength, on the other hand, from pH- and Km-shifts of immobilized enzymes. The accordance of potentials calculated from electrostatic and kinetic parameters confirms the macroscopic carrier-enzyme model.

Amylases↗

Cortical responses to stimulation of two functionally different thalamic nuclei in rats.

In acute experiments on adult rats we studied cortical responses to stimulation of two thalamic nuclei--a specific somatosensory relay nucleus (the ventral dorsomedial nucleus, VDM) and a nucleus without specific cortical projection (the lateral anterior nucleus, LA). The responses evoked from the two nuclei by various stimuli have the same basic form--an initial positive phase (inconstant in stimulation of the LA) is followed by dominant negativity and a late slow negative wave; the response ends with a rhythmic afterdischarge. Rhythmic stimulation of the thalamic nuclei produces incremental responses in the cortex and both the positive and the negative phase of the evoked potential participate in the amplitude changes. Hippocampocortical responses (which were compared with thalamocortical responses) have neither a late negative wave nor a distinct rhythmic afterdischarge; in rhythmic stimulation the amplitude of the responses seldom waxes and wanes. Study of the given cortical responses failed to explain the basic difference in the ability of the two thalamic nuclei to produce a self-sustained afterdischarge after rhythmic stimulation, when a spike-and wave rhythm was always elicited from the VDM, while in most cases a "hippocampal" type of self-sustained afterdischarge was evoked from the LA.

Animals↗

Changes in some parameters of the presynaptic bag in synapses of the somatosensory cortex of the rat brain after repetitive electrical stimulation prolonging self-sustained after-discharges. An electron microscopic morphometric study.

The sensorimotor area of the rat cerebral cortex was subjected to repeated electrical stimulation at 10 min intervals; this progressively prolonged the duration of self-sustained after-discharges (SSAD). Ten minutes after the third SSAD ended, the animals' brains were perfused with fixing fluid. The homotopic area of the contralateral hemisphere was examined electron microscopically. In type I synapses in the second cortical layer we determined A) the mean areas of sections of the presynaptic bag, B) the length of the active zone of the presynaptic bag, C) the mean total number of agranular synaptic vesicles per 0.01 micron2 area of the presynaptic bag in the experimental and control rats. In the experimental animals value A) rose by 34%, value B) by 14%, value C) by 95% and value D) by 52%. The differences are all statistically significant. Findings A) and B) are most likely evidence of ionic shifts, while findings C) and D) testify to the increase in the number of synaptic vesicles in the whole presynaptic bag and also to their redistribution towards the synaptic cleft. The possibility that findings C) and D) are the morphological correlate of increased synaptic transmission during experimental treatment leading to the kindling phenomenon cannot be ruled out.

Animals↗

Changes in the length and width of the postsynaptic density, the width of the intersynaptic density and the synaptic cleft in the cerebral cortex synapses of rats exposed to prolonged aerogenic hypoxia during early ontogenesis. An electron microscopic morphometric study.

Infant rats, together with the female, were exposed daily from birth to the age of 17 days (except for the 6th, 7th, 13th and 14th day) to a simulated attitude of 7,000 m. On the 18th day, 20 hours after the last exposure to hypoxia, the animals were perfused. In each of 118 synapses from the two control animals and 162 synapses from the two experimental animals (type I synapses, second cortical layer of the somatosensory cortex, impregnated with phosphotungstic acid), we measured A) the maximal thickness of the postsynaptic density and B) the minimal thickness of the postsynaptic density, C) estimated the thickness of the postsynaptic density and measured D) the distance between the pre- and the postsynaptic density, E) the thickness of the intersynaptic density and F) the length of the postsynaptic dense projection. In the experimental animals we found value A) to be 25% lower, value B) 28% lower, value C) 30% lower, value D) 5% lower, value E) 2.5% lower and value F) 17% higher than in the controls. The differences are statistically significant (evaluated by a t-test). It was found that, under our experimental hypobaric conditions, the maturation of synapses is retarded or modified.

Animals↗

[Methods of the selective demonstration of various structural elements of the vascular wall].

Selective topo-optical and impregnation technique for the demonstration of acid mucopolysaccharides, neutral polysaccharides, collagen, elastic fibres and membranes, smooth muscle cell i.e. structural elements of the vessel wall are described. These techniques are simple and reliable and may be used for the every-day pathohistological diagnostics. Their parallel application provides further possibilities for the study of the structure and various pathological alterations of the vessel wall. It should be stressed, that on the basis of the analysis of optical effects--birefringence, dichroism, metachromasia--these techniques provide opportunity to detect early structural lesions, which by the application of conventional techniques can not be detected.

Arteries↗

[Acute leukemia in multiple myeloma: case histories, a review of the literature and assessment of the incidence].

The results of a follow-up study of 112 patients with multiple myeloma are presented. Three of these patients developed acute leukaemia during the respective period of clinical observation (maximum: 11 years)--one case of acute myeloblastic leukaemia, myelomonocytic leukaemia and erythroleukaemia, respectively. For estimating the incidence of acute leukaemia in the presence of multiple myeloma an extended life table method was applied. On the basis of our data this method gave a probability of 5.9% for a patient to develop acute leukaemia at any time after the diagnosis of multiple myeloma. In a statistical discussion this result is considered to confirm the assumption of a highly increased AL-risk in patients with multiple myeloma. In a survey of the literature some important data of 100 cases with the association acute leukaemia--multiple myeloma are reported.

Acute Disease↗

Studies on the molecular arrangement of RNA in tissues with a selective topo-optical reaction of RNA.

Selective demonstration of RNA in tissues was achieved by treating tissue sections with potassium permanganate followed by bisulfite and toluidine blue at pH 1.0 (PBT reaction). It is suggested that this reaction is due to aldehyde groups which are formed by the oxidative cleavage of the pyrimidine rings of RNA which can be selectively demonstrated using bisulfite-toluidine blue as the aldehyde reagent. The specificity of the reaction was tested after RNAase treatment, after acid hydrolysis, and on pure RNA droplets. The aldehyde nature of the reacting groups was checked, after permanganate oxidation, by Schiff's leucofuchsin reagent, and by aldehyde blocking reactions. Two types of intracellular molecular arrangement of RNA molecules could be distinguished by polarization optics after application of the PBT reaction: 1) The strong birefringence, dichroism and metachromatic staining of membrane-bound RNA in ergastoplasm of pancreas, liver and plasma cells indicate a linear (planar) molecular order of RNA molecules on the surface of the membranes, and 2) the isotropic, basophilic staining of RNA not organized in membrane structures (Nissl substance, nucleoli) suggest a random distribution of their dye binding sites.

Animals↗

Mathematical modelling of ATP, K+ and Na+ interactions with (Na+ + K+)-ATPase occurring under equilibrium conditions.

The controlling effect of ATP, K+ and Na+ on the rate of (Na+ + K+)-ATPase inactivation by 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-C1) is used for the mathematical modelling of the interaction of the effectors with the enzyme under equilibrium conditions. 1. Of a series of conceivable interaction models, designed without conceptual restrictions to describe the effector control of inactivation kinetics, only one fits the experimental data described in a preceding paper. 2. The model is characterized by the coexistence of two binding sites for ATP and the coexistence of two separate binding sites for K+ and Na+ on the enzyme-ATP complex. On the basis of this model, the effector parameters fitting the experimental data most closely are estimated by means of nonlinear least-squares fits. 3. The apparent dissociation constants for ATP fo the enzyme-ATP complex or of the enzyme-(ATP)2 complex are computed to lie near 0.0024 mM and 0.34 mM, respectively, irrespective of whether K+ and Na+ were absent or K+ and K+ plus Na+, respectively, were present in the experiments. 4. The origin of the high and the low affinity site for binding of ATP to the (Na+ + K+)-ATPase molecule is traced back to the coexistence of two catalytic centres which, although primarily equivalent as to the reactivity of their thiol groups with NBD-C1, are induced into anticooperative communication by ATP binding and thus show an induced geometric asymmetry. 5. On the basis of the interaction model outlined under item 2 the apparent dissociation constant for K+ or Na+ in the (K+ + Na+)-liganded enzyme-ATP complex are computed to be 1.7 mM and 3.5 mM, respectively. 6. The conclusions concerning the coexistence of two primarily equivalent but anticooperatively interacting catalytic centres and the coexistence of two separate ionophoric centres for Na+ and K+ correspond to the appropriate basic postulates of the flip-flop concept of (Na+ + K+)-ATPase mechanism.

4-Chloro-7-nitrobenzofurazan↗