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Biomedical subjects

T Kiss

Publications and source records attributed to T Kiss.

At least 37 records · Page 2Linked to original sources

In vivo and in vitro effects of aluminum on the activity of mouse brain acetylcholinesterase.

Cholinesterases are a large family of enzymatic proteins widely distributed throughout both neuronal and non-neuronal tissues. In Alzheimer's disease (AD), analytical as well as epidemiological studies suggest an implication of an abnormal focal accumulation of aluminum in the brain. In this devastating disease, aluminum may interfere with various biochemical processes including acetylcholine metabolism, and can thus act as a possible etiopathogenic cofactor. Acetylcholinesterase (AChE) exists in several molecular forms that differ in solubility and mode of membrane attachment rather than in catalytic activity. Mice were treated orally with aluminum chloride or aluminum lactate (Al(lac)(3)), and AChE activity in their brain homogenates was then assayed. Results showed that this in vivo treatment augmented the activity of the enzyme. An activating effect was also observed in vitro, when the aluminum compounds were added directly to mouse brain homogenates. However, the activating effect observed in vivo was much more marked than that observed in vitro. In addition, the activation produced by Al(lac)(3) was higher than that obtained after aluminum chloride treatment. Kinetics measurements of AChE activity in the absence and presence of treatment with aluminum both in vivo and in vitro are reported. The influence of the metal speciation on enzymatic activity is discussed in relation to a possible implication of aluminum in some neurodegenerative diseases.

Acetylcholine↗

Synthesis and structural and spectroscopic characterization of a complex between Co(II) and imino-bis(methylphosphonic acid): gaining insight into biologically relevant metal-ion phosphonate interactions or looking at a new Co(II)-organophosphonate material?

Cobalt is an essential metal ion involved in key biomolecules, regulating processes in human physiology. As a metal ion, Co(II) assumes forms, which are dictated by the nature of organic binders in biological fluids, and the conditions under which metal ion ligand interactions arise. Among the various low molecular mass metal ion binders in biological fluids are amino acids, organic acids, as well as their variably phosphorylated forms. As a representative metal ion binder, the organophosphonate ligand H(2)O(3)P-CH(2)-NH(2)(+)-CH(2)-PO(3)H(-) was employed in aqueous reactions with Co(II), ultimately leading to the isolation of complex [Co(C(2)H(8)O(6)NP(2))(2)(H(2)O)(2)] (1) at pH 2. The complex was characterized analytically, spectroscopically (FTIR, UV-vis, EPR), and magnetically. Compound 1 crystallizes in the monoclinic space group P2(1)/n, with a = 7.361(3) A, b = 8.133(3) A, c = 14.078(5) A, beta = 104.40(1) degrees, V = 816.3(5) A(3), and Z = 2. X-ray crystallography reveals that 1 is a compound with a molecular type of lattice. In it, there exist mononuclear octahedral sites of Co(II) surrounded by oxygens, belonging to terminal phosphonates and bound water molecules. Both ends of the ligand zwitterionic form are involved in binding to adjacent Co(II) ions, thus creating tetranuclear 32-membered rings, with cavities extending in two dimensions and holes in the third dimension throughout the lattice of 1. Similar structural features were observed in other metal organophosphonate lattices of potential catalytic and chemical reactivity. The magnetic and EPR data on 1 support the presence of a high-spin octahedral Co(II) in an oxygen environment, having a ground state with an effective spin S = (1)/(2). The solution UV-vis and EPR data suggest retention of the high-spin octahedral Co(II) ion, consistent with the magnetization measurements on 1. Collectively, the data reflect the existence of a soluble Co(II)-iminodiphosphonate species not unlike those expected in biological fluids containing the specific ligand or ligands similar to that. Both biologically relevant perspectives and a synthetic outlook into Co(II)-organophosphonate materials are discussed.

Journal Article↗

Membrane effects of toxins isolated from a cyanobacterium, Cylindrospermopsis raciborskii, on identified molluscan neurones.

The effect of anatoxin (ANTX), the crude extract (AlgTX) and purified fraction (F1) isolated from cyanobacterium C. raciborskii was studied on the neurones of two snail species. ANTX and AlgTX exerted excitatory, inhibitory and biphasic effects on the spontaneous activity of identified neurones. Both ANTX and AlgTX elicited an inward current, which could be decreased by curare or amiloride. On the contrary, F1 had no direct effect on the spontaneous activity; it was not able to induce conductance changes of the neuronal membrane, but it did antagonise the acetylcholine (ACh)-induced inward current. We concluded that ANTX affects the neuronal membrane of neurones acting on ACh receptors. The AlgTX had similar effects, and therefore the extract of C. raciborskii may contain an ANTX-like component. The purified fraction prolonged and decreased the ACh-elicited response, but had no direct membrane effect. We suggest, therefore, that both AlgTX and the purified fraction F1 interact with the ACh receptor, but they have different binding sites on the neuronal ACh receptor-ion channel complex. The possible neurotoxic effects of the C. raciborskii extract and F1 are demonstrated for the first time; the molecular mechanism of their action, however, remains to be elucidated.

Acetylcholine↗

CT densitometry of the brain: a novel method for early detection and assessment of irradiation induced brain edema.

The purpose of the study was to examine if the CT densitometric analysis during radiotherapy (RT) of brain tumors is suitable for the early detection of RT induced brain edema (BE), predicting related neurological progress, and assessing the effects of different edema therapies. Planimetric CT-densitograms were constructed by modifying the "High-Lighting" method. Three theoretical density regions were defined and color-coded on the images of the brain. These were defined as edema (10-20 HU), mild edema, and normal brain (29-38 HU). Corresponding axial CT slices were created at the mid-level of the lesion and that of the periventricular white matter to verify the changes in perifocal and diffuse BE. The monitoring was performed on 50 solitary brain tumor patients treated with RT. During RT courses weekly CT-densitometric examinations were carried out. We experienced that changes in densitograms coincided with clinical symptoms, furthermore, preceded the latter. With the use of preventive edema medication based on diuretics and along with adjunctive edema medication adopted to densitograms, the 5-7 week irradiation was completed without ultimate worsening in performance state in 49 of 50 cases and besides we succeeded in avoiding the routine usage of steroids. Based on our findings the CT-densitometry is suitable for early detection and continuous assessment of BE and preventing patient distress during RT. This simple, reproducible and non-invasive procedure could provide an additional clinical tool for new treatment strategies.

Adult↗

Fermi surface sheet-dependent superconductivity in 2H-NbSe2.

High-resolution angle-resolved photoemission spectroscopy was used to study the superconducting energy gap and changes in the spectral function across the superconducting transition in the quasi-two-dimensional superconductor 2H-NbSe2. The momentum dependence of the superconducting gap was determined on different Fermi surface sheets. The results indicate Fermi surface sheet-dependent superconductivity in this low-transition temperature multiband system and provide a description consistent with thermodynamic measurements and the anomalous de Haas-van Alphen oscillations observed in the superconducting phase. The present data suggest the importance of Fermi surface sheet-dependent superconductivity in explaining exotic superconductivity in other multiband systems with complex Fermi surface topology, such as the borides and f-electron superconductors.

Journal Article↗

7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes.

The transcription of eukaryotic protein-coding genes involves complex regulation of RNA polymerase (Pol) II activity in response to physiological conditions and developmental cues. One element of this regulation involves phosphorylation of the carboxy-terminal domain (CTD) of the largest polymerase subunit by a transcription elongation factor, P-TEFb, which comprises the kinase CDK9 and cyclin T1 or T2 (ref. 1). Here we report that in human HeLa cells more than half of the P-TEFb is sequestered in larger complexes that also contain 7SK RNA, an abundant, small nuclear RNA (snRNA) of hitherto unknown function. P-TEFb and 7SK associate in a specific and reversible manner. In contrast to the smaller P-TEFb complexes, which have a high kinase activity, the larger 7SK/P-TEFb complexes show very weak kinase activity. Inhibition of cellular transcription by chemical agents or ultraviolet irradiation trigger the complete disruption of the P-TEFb/7SK complex, and enhance CDK9 activity. The transcription-dependent interaction of P-TEFb with 7SK may therefore contribute to an important feedback loop modulating the activity of RNA Pol II.

Binding Sites↗

Evidence for a multiple superconducting gap in MgB(2) from high-resolution photoemission spectroscopy.

We study the new binary intermetallic superconductor MgB(2) using high-resolution photoemission spectroscopy. The superconducting-state spectrum measured at 5.4 K shows a coherent peak with a shoulder structure, in sharp contrast to that expected from a simple isotropic-gap opening. The spectrum can be well reproduced using the weighted sum of two Dynes functions with the gap sizes of 1.7 and 5.6 meV. Temperature-dependent study shows that both gaps close at the bulk transition temperature. These results provide spectroscopic evidence for a multiple gap of MgB(2).

Journal Article↗

Serum concentrations of some metals and steroids in patients with chronic fatigue syndrome with reference to neurological and cognitive abnormalities.

Chronic fatigue syndrome is defined by the Atlanta Centers for Disease Control (Atlanta, GA, USA) as debilitating fatigue lasting for longer than 6 months. Symptoms include disturbances of cognition. Certain factors have in the past been shown to influence cognition, including metals such as aluminum, iron, and zinc; and steroids such as dehydroepiandrosterone. In the present study, concentrations of these factors were determined in the serum and plasma of patients and their age- and gender-matched healthy controls (10 women and 5 men in each group). In addition, copper, dehydroepiandrosterone sulphate, cortisol, cholesterol, hemoglobin, ferritin and transferrin concentrations, as well as transferrin genetic subtypes were determined in both groups. The results indicate that patients had significantly increased serum aluminum and decreased iron compared to controls. In the females, serum iron and dehydroepiandrosterone sulphate were significantly decreased and correlated. Total cholesterol was significantly increased, and significantly negatively correlated with dehydroepiandrosterone sulphate. There were no differences in zinc, copper, cortisol, hemoglobin, transferrin and ferritin concentrations, or in transferrin genetic subtypes.

Adult↗

Synthesis, pH-dependent structural characterization, and solution behavior of aqueous aluminum and gallium citrate complexes.

Reactions of Al(III) and Ga(III) with citric acid in aqueous solutions, yielded the complexes (NH(4))(5)[M(C(6)H(4)O(7))(2)].2H(2)O (M(III) = Al (1), Ga (2)) at alkaline pH, and the complexes (Cat)(4)[M(C(6)H(5)O(7))(C(6)H(4)O(7))].nH(2)O (M(III) = Al (3), Ga (4), Cat. = NH(4)(+), n = 3; M(III) = Al (5), Ga (6), Cat. = K(+), n = 4) at acidic pH. All compounds were characterized by spectroscopic (FT-IR, (1)H, (13)C, and (27)Al NMR, (13)C-MAS NMR) and X-ray techniques. Complex 1 crystallizes in space group P1, with a = 9.638(5) A, b = 9.715(5) A, c = 7.237(4) A, alpha = 90.96(1) degrees, beta = 105.72(1) degrees, gamma = 119.74(1) degrees, V = 557.1(3) A(3), and Z = 1. Complex 2 crystallizes in space group P1, with a = 9.659(6) A, b = 9.762(7) A, c = 7.258(5) A, alpha = 90.95(2) degrees, beta = 105.86(2) degrees, gamma = 119.28(1) degrees, V = 564.9(7) A(3), and Z = 1. Complex 3 crystallizes in space group I2/a, with a = 19.347(3) A, b = 9.857(1) A, c = 23.412(4) A, beta = 100.549(5) degrees, V = 4389(1) A(3), and Z = 8. Complex 4 crystallizes in space group I2/a, with a = 19.275(1) A, b = 9.9697(6) A, c = 23.476(1) A, beta = 100.694(2) degrees, V = 4432.8(5) A(3), and Z = 8. Complex 5 crystallizes in space group P1, with a = 7.316(1) A, b = 9.454(2) A, c = 9.569(2) A, alpha = 64.218(4) degrees, beta = 69.872(3) degrees, gamma = 69.985(4) degrees, V = 544.9(2) A(3), and Z = 1. Complex 6 crystallizes in space group P1, with a = 7.3242(2) A, b = 9.4363(5) A, c = 9.6435(5) A, alpha = 63.751(2) degrees, beta = 70.091(2) degrees, gamma = 69.941(2) degrees, V = 547.22(4) A(3), and Z = 1. The crystal structures of 1-6 reveal mononuclear octahedral complexes of Al(III) (or Ga(III)) bound to two citrates. Solution NMR, on both 4- and 5- species, reveals rapid intramolecular exchange of the bound and unbound terminal carboxylates. Upon dissolution in water, the complexes, through a complicated reaction cascade, transform to oligonuclear 1:1 species that, in agreement with previous studies, represent the thermodynamically stable state in solution. The data provide, for the first time, structural details of low MW, mononuclear complexes of Al(III) (or Ga(III)) with citrate that are dictated, among other factors, by pH. The properties of 1-6 may provide clues relevant to their biological association with humans.

Aluminum↗

A small nucleolar guide RNA functions both in 2'-O-ribose methylation and pseudouridylation of the U5 spliceosomal RNA.

In eukaryotes, two distinct classes of small nucleolar RNAs (snoRNAs), namely the fibrillarin-associated box C/D snoRNAs and the Gar1p-associated box H/ACA snoRNAs, direct the site-specific 2'-O-ribose methylation and pseudouridylation of ribosomal RNAs (rRNAs), respectively. We have identified a novel evolutionarily conserved snoRNA, called U85, which possesses the box elements of both classes of snoRNAs and associates with both fibrillarin and Gar1p. In vitro and in vivo pseudouridylation and 2'-O-methylation experiments provide evidence that the U85 snoRNA directs 2'-O-methylation of the C45 and pseudouridylation of the U46 residues in the invariant loop 1 of the human U5 spliceosomal RNA. The U85 is the first example of a snoRNA that directs modification of an RNA polymerase II-transcribed spliceosomal RNA and that functions both in RNA pseudouridylation and 2'-O-methylation.

Animals↗

Potentiometric and spectroscopic studies on the dimethyltin(IV) complexes of 2-hydroxyhippuric acid.

Equilibrium and spectroscopic (1H, 13C NMR and 119Sn Mössbauer) studies in aqueous solution are reported for dimethyltin(IV) complexes of 2-hydroxyhippuric acid (Sal-Gly). Below pH 4, oxygen-coordinated complexes MLH and ML are formed. In the pH range 5-8.5, the species MLH(-1), predominates at any metal-to-ligand ratio. The ligand exchange of this species is slow on the NMR time scale, which allows its structural characterization by NMR spectroscopy: the coordination polyhedron around the tin atom is distorted trigonal bipyramidal, with tridentate [O-,N-,COO-] coordination of Sal-Gly, involving two equatorial methyl groups. The NMR results reveal that the main cause of the distortion of the polyhedron is the large CH3-Sn-CH3 angle of 136+/-4 degrees. The presented results supplement the data available on the dimethyltin(IV)-promoted amide deprotonation of peptides, and provide further arguments for the fundamental role of the carboxylate as an anchoring group in this process.

Electrochemistry↗

Beta-galactosidase of Penicillium chrysogenum: production, purification, and characterization of the enzyme.

Intracellular beta-galactosidase from Penicillium chrysogenum NCAIM 00237 was purified by procedures including precipitation with ammonium sulfate, ion-exchange chromatography on DEAE-Sephadex, affinity chromatography, and chromatofocusing. These steps resulted a purification of 66-fold, a yield of about 8%, and a specific activity of 5.84 U mg(-1) protein. Some enzyme characteristics were determined using o-nitrophenyl-beta-d-galactopyranoside as substrate. The pH and temperature optimum of the activity were about 4.0 and 30 degrees C respectively. The K(m) and pI values were 1.81 mM and 4.6. beta-Galactosidase of P. chrysogenum is a multimeric enzyme of about 270 kDa composed of monomers with a molecular mass of 66 kDa.

Chromatography, Affinity↗

Hippocampal rhythm generation: gamma-related theta-frequency resonance in CA3 interneurons.

During different behavioral states different population activities are present in the hippocampal formation. These activities are not independent: sharp waves often occur together with high-frequency ripples, and gamma-frequency activity is usually superimposed on theta oscillations. There is both experimental and theoretical evidence supporting the notion that gamma oscillation is generated intrahippocampally, but there is no generally accepted view about the origin of theta waves. Precise timing of population bursts of pyramidal cells may be due to a synchronized external drive. Membrane potential oscillations recorded in the septum are unlikely to fulfill this purpose because they are not coherent enough. We investigated the prospects of an intrahippocampal mechanism supplying pyramidal cells with theta frequency periodic inhibition, by studying a model of a network of hippocampal inhibitory interneurons. As shown previously, interneulrons are capable of generating synchronized gamnma-requency action potential oscillations. Exciting the neurons by periodic current injection, the system could either be entrained in an oscillation with the frequency of the inducing current or exhibit in-phase periodic changes at the frequency of single cell (and network) activity. Simulations that used spatially inhomogeneous stimulus currents showed antiphase frequency changes across cells, which resulted in a periodic decrease in the synchrony of the network. As this periodic change in synchrony occurred in the theta frequency range, our network should be able to exhibit the theta-frequency weakening of inhibition of pyramidal cells, thus offering a possible mechanism for intrahippocampal theta generation.

Action Potentials↗

Complexes of aluminium(III) with glucose-6-phosphate in aqueous solutions.

The interaction of aluminium(III) with glucose-6-phosphate (GP: LH2) in aqueous solutions has been studied from pH 1 to pH 8, by pH-potentiometry and multinuclear (31P, 27Al, 13C) NMR spectroscopy. Various mononuclear species (MLH2, MLH, ML, ML2H, ML2 and MLH(-3)) and dinuclear complexes M2L2H-n (n=1-4) are formed in the system. NMR clearly indicates that GP is already bound to Al(III) at pH 1. The potentiometric speciation results are confirmed and completed by spectroscopic experiments. Many peaks are observed in the 31P NMR spectra suggesting the formation of isomeric species. An attempt to assign the signals to the corresponding complexes is made, allowing a discussion about their structure. Interestingly enough no metal ion-induced deprotonation and coordination of the alcoholic-OH functions have been observed.

Aluminum↗

The system VO2+ +oxidized glutathione: a potentiometric and spectroscopic study.

The equilibria in the system VO2+ +oxidized glutathione in aqueous solution have been studied in the pH range 2-11 by a combination of pH potentiometry and spectroscopy (EPR, visible absorption and circular dichroism). The results of the various methods are self-consistent and the equilibrium model includes the species MLH4, MLH3, MLH2, MLH, ML, MLH(-1), MLH(-2) and several hydrolysis products (where H4L denotes oxidized glutathione); individual formation constants and spectra are given. Plausible structures for each stoichiometry are discussed.

Circular Dichroism↗

Copper(II) and oxovanadium(IV) complexes of D-3-phosphoglyceric acid.

The complexes formed between D-3-phosphoglyceric acid and H(+), Cu(II) and VO(IV) were studied by pH-potentiometric and spectral (UV-Vis, EPR and CD) methods in order to describe the speciation of the metal ions and to determine the most probable binding modes in the complexes formed in these systems. The results show that, in the pH range between 2 and 4, mononuclear 1:1 complexes are formed through bidentate (MAH) or tridentate (MA) coordination of the ligand. At higher pH, when the proton competition for the central alcoholic-OH function decreases, alcoholate-bridged dinuclear species of composition M(2)A(2)H(-n) (n=1-3) become predominant. VO(IV) seems to have a higher tendency than Cu(II) to form such dinuclear complexes.

Copper↗