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Biomedical subjects

T Kiss

Publications and source records attributed to T Kiss.

At least 19 recordsLinked to original sources
PubMed2007

Solution behaviour and biological activity of bisamidine complexes of platinum(II).

A series of platinum(II) amidine complexes were previously prepared with the aim of obtaining a new class of platinum-based antitumour drugs. This series includes compounds of the type cis--[PtCl2{Z-HN=C(NHMe)Me}2] and trans-[PtCl2{Z-HN=C(NHMe)Me}2] (1, 2), cis-[PtCl2{E-HN=C(NMe2)Me}2] and trans-[PtCl2{E-HN=C(NMe2)Me}2] (3, 4), cis-[PtCl2{Z-HN=C(NHMe)Ph}2] and trans-[PtCl2{Z-HN=C(NHMe)Ph}2] (5, 6), and cis-[PtCl2{HN=C(NMe2)Ph}2] and trans-[PtCl2{HN=C(NMe2)Ph}2] (7, 8). The reactions with dimethyl sulfoxide were studied for complexes 5-8; the formation of cationic species containing coordinated dimethyl sulfoxide was demonstrated by NMR experiments and electrospray ionization mass spectrometry. In this work, the amidine platinum(II) complexes were tested for their in vitro cytotoxicity on a panel of various human cancer cell lines. The results indicate that the benzamidine complex 8 was the most effective derivative also circumventing acquired cisplatin resistance as demonstrated by chemosensitivity tests performed on cisplatin-sensitive and cisplatin-resistant cell lines. The studies concerning the cellular DNA damage on both parental chemosensitive and resistant sublines suggest for the new trans-amidine complex a different mechanism of action compared with that exhibited by cisplatin.

Amidines↗
PubMed2006

Solution equilibrium characterization of insulin-mimetic Zn(II) complexes.

Solution speciation (stoichiometry and stability constants) of the insulin mimetic Zn(II) complexes of several bidentate ligands with (O,O), (N,O) or (S,O) coordination modes have been determined by pH-metry at 25 degrees Celsius and I=0.2M (KCl). All ligands were found to coordinate in a bidentate way forming mono, bis and tris complexes, besides a mixed hydroxo bis complex ZnL(2)(OH) detected in the slightly basic pH range together with the tris complex. Relationships between the stability data, lipophilicity of the complexes and earlier biological data are evaluated. The validity of the linear free energy relationships (LFER) between the proton and Zn(II) complexes and also between the VO(IV) and Zn(II) complexes is tested.

Hydrogen-Ion Concentration↗
PubMed2006

Bulk- and surface-sensitive high-resolution photoemission study of two mott-hubbard systems: SrVO3 and CaVO3.

We study the electronic structure of Mott-Hubbard systems SrVO3 and CaVO3 with bulk and surface-sensitive high-resolution photoemission spectroscopy, using a vacuum ultraviolet laser, synchrotron radiation, and a discharge lamp (hv = 7-21 eV). A systematic suppression of the density of states (DOS) within approximately 0.2 eV of the Fermi level (EF) is found on decreasing photon energy, i.e., on increasing bulk sensitivity. The coherent band in SrVO3 and CaVO3 is shown to consist of surface and bulk-derived features, separated in energy. The stronger distortion on surface of CaVO3 compared to SrVO3 leads to a higher surface metallicity in the coherent DOS at EF, consistent with recent theory.

Journal Article↗
PubMed2006

Heavy-fermion-like state in a transition metal oxide LiV2O4 single crystal: indication of Kondo resonance in the photoemission spectrum.

We have performed a vacuum ultraviolet laser excited photoemission spectroscopy on a d-electron heavy-fermion-like material LiV2O4 single crystal. We observed a sharp peak structure in the density of states at approximately 4 meV above the Fermi level (E(F)). The evolution of the peak height corresponds well with the crossover behavior to the heavy-fermion-like state as observed in the thermal and transport properties. The position, shape, and temperature (T) dependence of the peak structure is quite similar to the Kondo resonance observed in conventional f-electron heavy Fermion compounds.

Journal Article↗
PubMed2006

From systems biology to dynamical neuropharmacology: proposal for a new methodology.

The concepts and methods of systems biology are extended to neuropharmacology in order to test and design drugs for the treatment of neurological and psychiatric disorders. Computational modelling by integrating compartmental neural modelling techniques and detailed kinetic descriptions of pharmacological modulation of transmitter-receptor interaction is offered as a method to test the electrophysiological and behavioural effects of putative drugs. Even more, an inverse method is suggested as a method for controlling a neural system to realise a prescribed temporal pattern. In particular, as an application of the proposed new methodology, a computational platform is offered to analyse the generation and pharmacological modulation of theta rhythm related to anxiety.

Action Potentials↗
PubMed2005

Persistent sodium current is a target for cAMP-induced neuronal plasticity in a state-setting modulatory interneuron.

We have identified a TTX-resistant low-threshold persistent inward sodium current in the cerebral giant cells (CGCs) of Lymnaea, an important state-setting modulatory cell type of molluscan feeding networks. This current has slow voltage-dependent activation and de-activation kinetics, ultra-slow inactivation kinetics and fast de-inactivation kinetics. It activates at approximately -90 mV, peaks at approximately -30 mV, reverses at approximately +35 mV and does not show full voltage-dependent inactivation even at positive voltage steps. Lithium-sodium replacement experiments indicate that the persistent sodium current makes a significant contribution to the CGC membrane potential. Injection of cyclic adenosine monophosphate (cAMP) into the CGC cell body produces a large increase in the persistent sodium current that lasts for several hours. cAMP injection also leads to increased bursting, a significant decrease in the resistance and a significant depolarization of the soma membrane, indicating that cAMP-dependent mechanisms induce prolonged neuronal plasticity in the CGCs. Our observations provide the first link between cAMP-mediated modulation of a TTX-resistant persistent sodium current and prolonged neuronal plasticity in an identified modulatory cell type that plays an important role in behavioral state setting.

Action Potentials↗
PubMed2005

Photoemission spectroscopic evidence of gap anisotropy in an f-electron superconductor.

We used low-temperature ultrahigh-resolution (360 microeV) photoemission spectroscopy with a laser as a photon source (Laser-PES) to study the superconducting (SC) gap of an f-electron superconductor CeRu2. The unique combination of the large escape depth expected from the known universal behavior and extremely high-energy resolution has enabled us to directly measure the bulk SC gap of an f-electron superconductor for the first time. The present study provides direct evidence for an anisotropic SC gap in CeRu2, and also demonstrates the potential of Laser-PES in investigating unconventional superconductivity realized in correlated d- and f-electron superconductors.

Journal Article↗
PubMed2005

Speciation study of an imidazolate-bridged copper(II)-zinc(II) complex in aqueous solution.

The solution equilibrium and the binding mode of the species in the five-component system containing two metal ions (copper(II) and zinc(II)) and three ligands (A=diethylenetriamine, B=imidazole, C=tris(2-aminoethyl)amine) were investigated by pH-potentiometric titration, UV-visible spectrophotometry and EPR (electron paramagnetic resonance) spectroscopic titration in aqueous solution in the 2-11 pH range. An imidazolate-bridged heterobinuclear complex (ACuBH(-1)ZnC) was found to evolve above pH=7 and was stable between pH 7 and 11. The existence of the ACuBH(-1)ZnC complex (by determination of its molecular weight) was proved by mass spectrometry (ESI-MS (electrospray ionization mass spectrometry) and MALDI (matrix-assisted laser desorption/ionization) techniques). The electrochemical behaviour and the superoxide dismutase activity of this complex were also tested by cyclic voltammetry and the Riboflavin/NBT (nitro blue tetrazolium) assay, respectively.

Binding Sites↗
PubMed2005

The relationship between mouthrinse matrix metalloproteinases (MMP-1, 8, 13) and albumin levels with the degree of oral mucositis in allogeneic stem cell transplant patients.

Our aim was to examine the relationship between mouthrinse matrix metalloproteinases (MMPs) and whole albumin levels (AL) relative to oral mucositis (OM) in allogeneic stem cell transplant (alloSCT) patients. Mouthrinse vertebrate collagenase levels are positively correlated with connective tissue destruction (CTD) in periodontitis and may also be involved in CTD associated with OM. Increases in salivary AL have been noted prior to OM onset and may serve as a predictive tool for OM and as a positive control in this study. A total of 23 alloSCT patients were visited eight times over 4 weeks following the transplant. OM was scored via a previously validated examiner-based ordinal system. Mouthrinse samples were collected and analyzed for MMP-1, 8, 13 (members of the vertebrate collagenase group) and AL. No significant correlation was found for MMP levels relative to OM scores. AL were positively and significantly associated with OM scores (P<0.001). MMP levels may not be an important factor in OM development and severity; however, mouthrinse AL may serve as a more objective measure of OM development and severity.

Adult↗
PubMed2004

Experimental evidence for the p-d hybridization in the Cd-Ca quasicrystal: origin of the pseudogap.

Ca 2p-3d resonant photoemission spectroscopy of a Cd6Ca crystalline approximant unambiguously demonstrates that the low-lying unoccupied 3d levels of calcium are lowered below the Fermi energy by the formation of the approximant, as suggested from electronic structure calculations [Phys. Rev. Lett. 87, 206408 (2001)]]. Moreover, the Ca 3d partial density of states (DOS) obtained near the Fermi energy is in reasonable agreement with theoretical Ca 3d DOS. These results verify the unconventional picture that the origin of the pseudogap in the Cd-based quasicrystals is due to hybridization of the Ca 3d band with the Cd 5p band.

Journal Article↗
PubMed2004

Modulation of septo-hippocampal Theta activity by GABAA receptors: an experimental and computational approach.

Theta frequency oscillation of the septo-hippocampal system has been considered as a prominent activity associated with cognitive function and affective processes. It is well documented that anxiolytic drugs diminish septo-hippocampal oscillatory Theta activity contributing to their either therapeutic or unwanted side effects. In the present experiments we applied a combination of computational and physiological techniques to explore the functional role of GABAA receptors in Theta oscillation. In electrophysiological experiments extracellular single unit recordings were performed from medial septum/diagonal band of Broca with simultaneous hippocampal (CA1) electroencephalogram (EEG) recordings from anesthetized rats. Neurotransmission at GABAA receptors were modulated by means of pharmacological tools: the actions of the GABAA receptor positive allosteric modulator diazepam and inverse agonist/negative allosteric modulator FG-7142 were evaluated on septo-hippocampal activity. Systemic administration of diazepam inhibited, whereas FG-7142 enhanced Theta oscillation of septal neurons and hippocampal EEG Theta activity. In parallel to these experimental observations, a computational model has been constructed by implementing a septal GABA neuron model with a CA1 hippocampal model containing three types of neurons (including oriens and basket interneurons and pyramidal cells; latter modeled by multicompartmental techniques; for detailed model description with network parameters see online addendum: http://geza.kzoo.edu/theta). This connectivity made the network capable of simulating the responses of the septo-hippocampal circuitry to the modulation of GABAA transmission, and the presently described computational model proved suitable to reveal several aspects of pharmacological modulation of GABAA receptors. In addition, computational findings indicated different roles of distinctively located GABAA receptors in theta generation.

Animals↗
PubMed2004

The role of allogeneic bone marrow transplantation in adult patients below the age of 55 years with acute lymphoblastic leukemia in first complete remission: a donor vs no donor comparison.

The role of allogeneic bone marrow transplantation (alloBMT) in adults with acute lymphoblastic leukemia (ALL) in first complete remission (CR1) remains controversial. At our institution, the policy is to offer alloBMT to ALL patients in CR1 up to the age of 55 years if a related donor is available. In addition, unrelated donor transplants are offered to patients with Philadelphia (Ph+) ALL. We report the results on 92 patients with ALL treated according to this policy from September 1992 to October 2001. Of the 87 patients achieving CR1, the comparison of patients with (n=48) or without donors (n=39) was done using an intention-to-treat approach. Of the 48 patients with donors (39 related and nine unrelated), 35 (73%) received alloBMT in CR1. No significant difference in 3-year event-free survival (EFS) (40 vs 39%, P=0.74) or overall survival (OS) (46 vs 58%, P=0.41) was seen in 'donor' vs 'no-donor' groups. For Ph+ patients, 3-year EFS and OS in 'donor' group were 46 and 57%, respectively, none of the patients in 'no-donor' group survived beyond 3 years. With our treatment strategy, 3-year OS of Ph+ patients was equivalent to Ph-negative (Ph-) patients (51 vs 52%, P=0.77). In conclusion, our data show that the policy of performing alloBMT if a sibling donor is available has not resulted in better outcome in Ph- patients.

Adolescent↗
PubMed2004

Functional morphology of the salivary gland of the snail, Helix pomatia: a histochemical and immunocytochemical study.

Functional morphology of Helix pomatia salivary gland cells was studied at light microscopic level by using different histochemical methods. Three cell types could be demonstrated in the salivary gland: mucocytes, granular and vacuolated cells. The distribution and the number of the different cell types were different in active and inactive snails. In active feeding animals, dilatated interlobular salivary ducts were observed, which were never present in inactive ones. In active animals an additional cell type, the cystic cell could also be observed. Periodic acid Schiff staining revealed both mucuos and serous elements in the salivary gland. Furthermore, hematoxyline-eosin staining indicated the occurrence of a cell layer with high mitotic activity in the acini. Applying immunohistochemical methods with monoclonal mouse anti-human Ki-67 clone, B56 and polyclonal rabbit anti-human Ki-67 antibodies, we also were able to demonstrate the occurrence of dividing cells in the salivary gland. Analysis of 1-2 microm semi-thin Araldite sections stained with toluidine-blue showed that the saliva can be released, in addition to possible exocytosis, by the lysis of cystic cells. Using an apoptosis kit, we could also establish that this process was due to rather an apoptotic than a necrotic mechanism. In the salivary gland of active snails, where an intensive salivation takes place, significantly more apoptotic cells occurred, if compared to that of inactive animals. It is suggested that programmed cell death may also be involved in the saliva release.

Animals↗
PubMed2003

Correlations of synthetic, spectroscopic, structural, and speciation studies in the biologically relevant cobalt(II)-citrate system: the tale of the first aqueous dinuclear cobalt(II)-citrate complex.

Synthetic efforts targeting soluble species of Co(II) with the low molecular mass physiological ligand citric acid led to the isolation of the first dinuclear complex [Co(2)(C(6)H(5)O(7))(2)(H(2)O)(4)](2-), at pH approximately 5, in the form of its K+ (1) and Na+ (2) salts. Both 1 and 2 were characterized analytically, spectroscopically (FT-IR, UV/visible, EPR), and magnetically. Complex 1 crystallizes in the monoclinic space group P2(1)/n, with a = 10.348(5) A, b = 11.578(6) A, c = 12.138(6) A, beta = 112.62(2) degrees, V = 1342(1) A(3), and Z = 2. Complex 2 crystallizes in the monoclinic space group P2(1)/c, with a = 9.234(4) A, b = 11.913(4) A, c = 11.728(6) A, beta = 99.93(2) degrees, V = 1271(1) A(3), and Z = 2. X-ray crystallography on 1 and 2 reveals the presence of two Co(II) ions, in a dinuclear assembly, octahedrally coordinated by two citrate ligands in a tridentate fashion. The octahedral environment around each Co(II) is complemented by another singly bonded citrate belonging to the adjacent Co(II) unit and two water molecules. Magnetic susceptibility and EPR studies on 1, in the solid state, corroborate the X-ray results, indicating a weak interaction between the two Co(II) ions. Moreover, EPR and UV/visible studies in solution suggest that 1 does not retain its dimeric structure, yielding a mononuclear octahedral Co(II)-citrate species. Detailed speciation studies suggest the presence of a number of species including the mononuclear complex [Co(C(6)H(5)O(7))](-), optimally present around pH approximately 5. In consonance with EPR and UV/visible spectroscopy, [Co(C(6)H(5)O(7))](-) is likely the scaffolding unit on the basis of which the dimer [Co(2)(C(6)H(5)O(7))(2)(H(2)O)(4)](2-) is isolated from aqueous solutions. Collectively, this comprehensive study offers significant structural insight into the Co(II)-citrate speciation and the elucidation of the role of Co(II) in biological fluids.

Journal Article↗
PubMed2003

Dopamine and serotonin receptors mediating contractions of the snail, Helix pomatia, salivary duct.

The combination of high performance liquid chromatography, bioassay and immunocytochemistry was applied to study the regulation of the salivary duct muscle of the snail, Helix pomatia. The major function of the duct appears to be to propel the saliva toward the buccal cavity during feeding. It has been established that serotonin and dopamine applied exogenously mimic the effect on the duct exerted by the stimulation of the salivary nerve. Immunohistochemistry revealed the presence of serotonin, but not dopaminergic nerve elements in the nerve and along the duct surface. However, both serotonin (14.9-15.5 pmol/mg) and dopamine (0.38-0.58 pmol/mg), as well as the synthesizing enzymes (tyrozine hydroxylase 0.28 pmol/mg tissue/h and DOPA 0.32 nmol synthesized DA/mg tissue/h) could regularly be assayed in the salivary duct by high performance liquid chromatography. When released following the stimulation of the salivary nerve, both monoamines were shown to interact with distinct membrane receptors. Dopamine elicited a sustained increase of the muscle tone in concentration-dependent manner (K(d)=1.5 microM). Mammalian D(1) receptor antagonist flupenthixol and fluphenazine attenuated, whereas the D(1) receptor agonist SKF-38393 mimicked the effect elicited by exogenous dopamine. Serotonin had a double effect on the salivary duct: a relaxing and a contracting one with different K(d) values 76 nM and 2.4 microM, respectively. 5-HT(2) receptor antagonist ritanserin and ketanserin attenuated the serotonin-induced relaxation. In contrast 5-HT(3) antagonist metoclopramide and MDL2222 decreased and 5-HT(3) receptor agonist 1-(m-chlorophenyl)-biguanide mimicked the serotonin-induced contraction, suggesting that serotonin exerted its action on two different receptor subtypes. The release of radiolabeled serotonin and dopamine upon nerve stimulation was found to be Ca-dependent. Furthermore, the increase in serotonin concentration induced a decrease of the potency of dopamine to elicit sustained contraction. These results provide evidence for the transmitter role of serotonin and dopamine in salivary duct. It is concluded that receptors reveal a pharmacological profile related to vertebrate D(1), 5-HT(2) and 5-HT(3) receptor subtypes. Moreover, it was found that the process of conveying the saliva is modulated by an interaction of dopamine and serotonin.

Animals↗
PubMed2003

Stem cell transplantation for myelofibrosis: a report from two Canadian centers.

We describe the course of 25 patients with myelofibrosis (MF) due to agnogenic myeloid metaplasia (n=19) or essential thrombocytosis (n=6) who underwent allogeneic stem cell transplantation (SCT) at one of two Canadian centers. The median age at transplantation was 48.7 (IQR 45.9-50.4) years and transplantation was carried out at a median of 10.7 (IQR 5.67-26.5) months after diagnosis. Granulocyte engraftment (absolute neutrophil count >0.5 x 109/l) occurred at a median of 20 days after transplantation for splenectomized patients, compared with 27.5 days for nonsplenectomized individuals (P=0.03). Increased risk of grade II-IV acute graft-versus-host disease (P=0.04) was noted in patients transplanted after splenectomy. Patients with MF received 0.264+/-0.189 U of packed red blood cells per day over the first 180 days after transplantation, and remained dependent on red blood cell transfusions for a median of 123 (IQR 48-205) days. Complete remission of MF was documented in 33% of evaluable patients. The 1 year cumulative nonrelapse mortality was 48.3%. Median survival for this group of patients was 393 (IQR 109-1014+) days, with a projected 2-year overall survival of 41%. We conclude that allogeneic SCT offers a reasonable chance for prolonged survival in patients with advanced MF, but this occurs at the cost of considerable toxicity and nonrelapse mortality.

Erythrocyte Transfusion↗