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Péter Nagy

Publications and source records attributed to Péter Nagy.

At least 19 recordsLinked to original sources
PubMed2007

Kinetics and mechanism of the comproportionation of hypothiocyanous acid and thiocyanate to give thiocyanogen in acidic aqueous solution.

The kinetics of comproportionation of hypothiocyanous acid (HOSCN) and thiocyanate (SCN-) to give thiocyanogen ((SCN)2) in acidic aqueous solutions have been determined by double-mixing stopped-flow UV spectroscopy. Hypothiocyanite (OSCN-) was generated at pH 13 by oxidation of excess SCN- with hypobromite (OBr-), followed by a pH jump to acidic conditions ([H+] = 0.20-0.46 M). The observed pseudo-first-order rate constants exhibit first-order dependencies on [H+] and [SCN-] with overall third-order kinetics. The corresponding kinetics of hydrolysis of (SCN)2 have also been examined. Under conditions of high (and constant) [H+] and [SCN-], the kinetics exhibit second-order behavior with respect to [(SCN)2] and complex inverse dependences on [H+] and [SCN-]. Under conditions of low [H+] and [SCN-], the kinetics exhibit first-order behavior with respect to [(SCN)2] and independence with respect to [H+] and [SCN-]. We attribute this behavior to a shift in the rate-limiting step from disproportionation of HOSCN (second-order dependency on [(SCN)2]) to rate-limiting hydrolysis (first-order dependency on [(SCN)2]). Thus, we have determined the following equilibrium constant by the kinetic method: (SCN)2 + H2O HOSCN + SCN- + H+; Khyd = [HOSCN][SCN-][H+]/[(SCN)2] = khyd/kcomp = 19.8(+/-0.7) s-1/ 5.14(+/-0.07) x 103 M-2 s-1 = 3.9 x 10-3 M2.

Hydrogen-Ion Concentration↗
PubMed2007

Kinetics and mechanism of the oxidation of the glutathione dimer by hypochlorous Acid and catalytic reduction of the chloroamine product by glutathione reductase.

Oxidized glutathione (GSSG) reacts with two molar equivalents of HOCl/OCl- (a neutrophil-derived oxidant and a common biocide) to form the dichloro (bis-N-chloro-gamma-l-glutamyl) derivative (NDG). The reaction of less than two molar equivalents of HOCl with GSSG does not yield the unsymmetrical monochloro derivative (NCG) but rather a stoichiometric amount of NDG and GSSG. This result is explained by a faster reaction of the second equivalent of HOCl with NCG than that of the first equivalent of HOCl with GSSG. The rates of reaction of GSSG2-, GSSG3-, and GSSG4- (successive deprotonation of the ammonium groups) have been investigated, and it is clear that GSSG2- is unreactive, whereas GSSG4- is about twice as reactive as GSSG3-. Accordingly, the following mechanism is proposed (constants for 5 degrees C): H+ + OCl- = HOCl, pK1 = -7.47; GSSG2- = GSSG3- + H+, pK2 = 8.5; GSSG3- = GSSG4- + H+, pK3 = 9.5; GSSG3- + HOCl --> NCG3- + H2O, k4 = 2.7(2) x 106 M-1 s-1; GSSG4- + HOCl --> NCG4- + H2O, k5 = 3.5(3) x 107 M-1 s-1; NCG3- --> NDG4- + H+, k6 = fast; and NCG4- + HOCl --> NDG4- + H2O, k7 = fast. At physiologic pH, the k4 pathway dominates. NDG decomposes at pH 7.4 in a first-order process with kdec = 4.22(1) x 10-4 s-1 (t1/2 = 27 min). Glutathione reductase (EC 1.6.4.2) is capable of catalyzing the reduction of NDG by NADPH. The only NDG-derived product that is observed (by NMR) after the reduction by NADPH is GSH. Thus, in the presence of the GOR/NADPH system, GSH is capable of redox buffering a 3/2 mol equiv of HOCl rather than a 1/2 mol equiv as previously assumed.

Catalysis↗
PubMed2006

Lactoperoxidase-catalyzed oxidation of thiocyanate by hydrogen peroxide: a reinvestigation of hypothiocyanite by nuclear magnetic resonance and optical spectroscopy.

In an effort to reconcile conflicting reports regarding the spectra of the human defense factor hypothiocyanite (OSCN(-)), we have synthesized OSCN(-) by three methods and characterized the product spectroscopically. Method I is lactoperoxidase-catalyzed oxidation of SCN(-) by H(2)O(2) at pH 7. Method II is hydrolysis of (SCN)(2) at pH 13. Method III is oxidation of SCN(-) by OX(-) (X = Cl and Br) at pH 13. All three methods produced essentially the same initial UV, (13)C NMR, and (15)N NMR spectra. The UV spectrum reveals a lambda(max) of 376 nm, which is a previously unreported distinguishing feature. The (13)C NMR spectrum (delta = 127.8 ppm at pH 13 vs dioxane at 66.6 ppm) is comparable to those that have been previously reported for OSCN(-) as prepared by methods I and II (although in some cases different assignments have been made). However, the (15)N NMR spectrum we measure (delta = -80.6 ppm at pH 13 vs NO(3)(-) at 0 ppm) contrasts with previous reports. We conclude that all three methods produce the same species, and the spectra are now self-consistent with the formulation OSCN(-).

Carbon Isotopes↗
PubMed2006

[Hepatocarcinogenesis in human liver].

Due to the development of the imaging techniques and liver surgery, pathologists are encountered more frequently with preneoplastic liver lesions. Well-defined stages of human hepatocarcinogenesis have been distinguished recently. Dysplastic foci represent the earliest stage of this process. Small-cell dysplastic foci are tumor precursors, but the large-cell form of this lesion does not progress further. The next stage is the dysplastic nodule, this larger lesion can be recognized by imaging techniques and gross examination of the specimen. Low- and high-risk forms are distinguished based on the level of cytological and structural atypia. The small hepatocellular carcinomas have a diameter of less than 2 cm by definition. The small HCC of indistinctly nodular type is equivalent of in situ carcinomas in other organs and designated sometimes as early HCC. The small HCC of the distinctly nodular type can be interpreted as advanced cancer despite its small size. The distinction between these lesions can be facilitated by ancillary techniques. The so-called capillarization of the liver sinusoids during the progression is characterized by the increased expression of endothelial markers as CD31 and CD34. Immunostaining for CD44, beta-catenin and p53 has prognostic value. Molecular biological techniques reveal gradual epigenetic and DNA changes during the process of hepatocarcinogenesis. Global gene expression profiling of hepatocellular carcinomas may result in a new classification of this tumor and can reveal new potential therapeutic targets.

Biomarkers, Tumor↗
PubMed2006

Thiocyanate is an efficient endogenous scavenger of the phagocytic killing agent hypobromous acid.

Second-order rate constants for the reaction of HOBr/OBr- (a putative killing agent of eosinophils and a reactive oxygen species that is implicated in mutagenesis and in human inflammatory diseases) with SCN- (an endogenous species in human physiologic fluids) are determined by stopped-flow spectroscopy. The proposed mechanism includes parallel pathways with Br+ transfer to SCN- by general acid catalysis and by direct reaction with HOBr. HOBr reacts with SCN- with a second-order rate constant (2.3 x 10(9) M(-1) s(-1)) that is 2 orders of magnitude larger than that previously measured for the reaction of HOCl with SCN- (2.3 x 10(7) M(-1) s(-1)), and very close to the diffusion limit. In contrast to OCl-, OBr- exhibits a measurable rate of reaction with SCN- (3.8 x 10(4) M(-1) s(-1)). On a molar basis, SCN- is the most effective scavenger of HOBr to be reported to date (200 times more effective than cysteine and 650 times more effective than methionine). Computational models suggest that SCN- is competitive with respect to other scavengers at physiologically relevant concentrations, which leads us to propose it may limit the lifetime of HOBr and its propensity to inflict host tissue damage during inflammatory response, especially during eosinophilia. Furthermore, the product of the nonenzymatic reaction of HOBr and SCN-, hypothiocyanite (OSCN-), is an effective antimicrobial that is relatively innocuous toward mammalian cell lines. Since one of the principal charges of eosinophil cells is to clear extracellular parasites via nonphagocytic mechanisms that involve degranulation of eosinophil peroxidase (EPO, the principal mammalian enzyme that produces HOBr), a larger role for OSCN- is suggested for parasitic infection.

Bromates↗
PubMed2005

Metal-metal bond or isolated metal centers? Interaction of Hg(CN)2 with square planar transition metal cyanides.

Three adducts have been prepared from Hg(CN)(2) and square planar M(II)(CN)(4)(2)(-) transition metal cyanides (M = Pt, Pd, or Ni, with d(8) electron shell) as solids. The structure of the compounds K(2)PtHg(CN)(6).2H(2)O (1), Na(2)PdHg(CN)(6).2H(2)O (2), and K(2)NiHg(CN)(6).2H(2)O (3) have been studied by single-crystal X-ray diffraction, XPS, Raman spectroscopy, and luminescence spectroscopy in the solid state. The structure of K(2)PtHg(CN)(6).2H(2)O consists of one-dimensional wires. No CN(-) bridges occur between the heterometallic centers. The wires are strictly linear, and the Pt(II) and Hg(II) centers alternate. The distance d(Hg)(-)(Pt) is relatively short, 3.460 A. Time-resolved luminescence spectra indicate that Hg(CN)(2) units incorporated into the structure act as electron traps and shorten the lifetime of both the short-lived and longer-lived exited states in 1 compared to K(2)[Pt(CN)(4)].2H(2)O. The structures of Na(2)PdHg(CN)(6).2H(2)O and K(2)NiHg(CN)(6).2H(2)O can be considered as double salts; the lack of heterometallophilic interaction between the remote Hg(II) and Pd(II) atoms, d(Hg)(-)(Pd) = 4.92 A, and Hg(II) and Ni(II) atoms, d(Hg)(-)(Ni) = 4.61 A, is apparent. Electron binding energy values of the metallic centers measured by XPS show that there is no electron transfer between the metal ions in the three adducts. In solution, experimental findings clearly indicate the lack of metal-metal bond formation in all studied Hg(II)-CN(-)-M(II)(CN)(4)(2)(-) systems (M = Pt, Pd, or Ni).

Journal Article↗
PubMed2005

The role of supramolecular protein complexes and membrane potential in transmembrane signaling processes of lymphocytes.

The formation of protein patterns in lymphocyte plasma membranes is analyzed in the light of past and, also, very recent experiments. The analysis surveys the lateral organization of major histocompatibility complex glycoproteins, intercellular adhesion molecule-1, interleukin-2 and -15 receptors, Kv1.3 K+ ion channels and the T-cell receptor as well as their behavior under different conditions. These molecules form small- and large-scale clusters in the membrane of human lymphocytes. Many of the association motifs occur in other investigated cell types. The conclusions point toward a possible role for ion channel activities, membrane potential changes and alterations of the lateral organization of proteins in transmembrane signaling and cytotoxic interactions. In our outlook new factors that potentially affect membrane protein cluster formation and interactions are discussed. A role for MHC glycoproteins in concentrating membrane proteins and organizing protein patterns is suggested, and the possibility that the membrane potential may modulate protein conformation and, thereby, affect protein-protein interactions is pointed out. A well-defined role for the presence of ion channels in the immune synapse is offered, which could explain the significance of ion channel accumulation in the immune synapse together with the T-cell receptor.

Animals↗
PubMed2005

Associations of ErbB2, beta1-integrin and lipid rafts on Herceptin (Trastuzumab) resistant and sensitive tumor cell lines.

ErbB2-mediated transmembrane signaling is a key target of novel anticancer agents such as Herceptin. Our comparison of Herceptin resistant (JIMT-1, MKN-7) and sensitive (SKBR-3, N-87) cell lines demonstrates the importance of ErbB2 association patterns involving integrins and lipid rafts. Flow cytometric FRET and confocal microscopic measurements revealed colocalization and molecular proximity between beta1-integrins and ErbB2, as well as their association with lipid rafts. A weak functional interaction between ErbB2 and beta1-integrin and the fact that ErbB2 did not co-patch with beta1-integrins upon crosslinking imply that ErbB2 and beta1-integrin define two distinct molecular association clusters from a functional point of view. Although Herceptin-sensitive cell lines expressed more ErbB2 and fewer beta1-integrin molecules on their surface than their resistant counterparts, this finding probably does not explain the Herceptin resistant phenotype due to the weak interaction between beta1-integrins and ErbB2. Our results imply that the true significance of the expression profile of proteins involved in oncogenesis can only be understood after characterizing their molecular interactions.

Antibodies, Monoclonal↗
PubMed2005

Alpha-fetoprotein expression is a potential prognostic marker in hepatocellular carcinoma.

AIM: To characterize the alpha-fetoprotein (AFP) positive and negative hepatocellular carcinoma (HCC) samples. METHODS: Thirty-seven paraffin-embedded human HCC samples were analyzed by immunohistochemistry for the following antigens: AFP, beta-catenin, p53, CD44, MSH-2, MLH-1, and HNF-4. The tumors were divided into two groups based on the AFP expression. The immunophenotypic data and important clinical parameters were studied between the two groups. RESULTS: Twenty-one of the thirty-seven examined HCCs were AFP positive. Seven with nuclear p53 staining were AFP positive, while seven tumors with nuclear beta-catenin staining were AFP negative. CD44 staining and high histological tumor grade were more frequent among the AFP-positive HCCs. The other immunophenotypical and clinical parameters did not show statistically significant difference in their distribution between the AFP positive and negative samples. CONCLUSION: AFP expression in HCC correlates with unfavorable prognostic factors, while nuclear beta-catenin positivity is more common among the AFP-negative liver tumors. This observation supports the microarray data on in vivo human tumors.

Biomarkers, Tumor↗
PubMed2005

Development of the vasculature in "pushing-type" liver metastases of an experimental colorectal cancer.

A mechanism for stroma formation (development of vasculature and supportive connective tissue) is suggested in an experimental "pushing-type" colorectal carcinoma liver metastasis model. The key element is the appearance of smooth muscle actin (SMA)-positive cells and the sinusoidal lakes at the border of the metastases. These lakes are the consequence of the disappearance ('stepping back' of hepatocytes from the border zone, resulting in the fusion of partially capillarized sinusoids. The growing tumor incorporates SMA-expressing cells and sinusoidal lakes. SMA-positive cells produce collagenous matrix, whereas the lakes become the central vessels within the connective tissue columns. Formation of these columns within the tumor is a consequence of the compression atrophy of the base of the incorporated liver tissue, leading to partial separation of the innermost part of the invagination containing functional vessel(s) from the surrounding liver.

Actins↗
PubMed2005

Solubility, complex formation, and redox reactions in the Tl2O3-HCN/CN(-)-H2O system. Crystal structures of the cyano compounds Tl(CN)3.H2O, Na[Tl(CN)4].3H2O, K[Tl(CN)4], and Tl(I)[Tl(III)(CN)4] and of Tl(I)2C2O4.

Thallium(III) oxide can be dissolved in water in the presence of strongly complexing cyanide ions. Tl(III) is leached from its oxide both by aqueous solutions of hydrogen cyanide and by alkali-metal cyanides. The dominating cyano complex of thallium(III) obtained by dissolution of Tl2O3 in HCN is [Tl(CN)3(aq)] as shown by 205Tl NMR. The Tl(CN)3 species has been selectively extracted into diethyl ether from aqueous solution with the ratio CN-/Tl(III) = 3. When aqueous solutions of the MCN (M = Na+, K+) salts are used to dissolve thallium(III) oxide, the equilibrium in liquid phase is fully shifted to the [Tl(CN)4]- complex. The Tl(CN)3 and Tl(CN)4- species have for the first time been synthesized in the solid state as Tl(CN)3.H2O (1), M[Tl(CN)4] (M = Tl (2) and K (3)), and Na[Tl(CN)4].3H2O (4) salts, and their structures have been determined by single-crystal X-ray diffraction. In the crystal structure of 1, the thallium(III) ion has a trigonal bipyramidal coordination with three cyanide ions in the equatorial plane, while an oxygen atom of the water molecule and a nitrogen atom from a cyanide ligand, attached to a neighboring thallium complex, form a linear O-Tl-N fragment. In the three compounds of the tetracyano-thallium(III) complex, 2-4, the [Tl(CN)4]- unit has a distorted tetrahedral geometry. Along with the acidic leaching (enhanced by Tl(III)-CN- complex formation), an effective reductive dissolution of the thallium(III) oxide can also take place in the Tl2O3-HCN-H2O system yielding thallium(I), while hydrogen cyanide is oxidized to cyanogen. The latter is hydrolyzed in aqueous solution giving rise to a number of products including (CONH2)2, NCO-, and NH4+ detected by 14N NMR. The crystalline compounds, Tl(I)[Tl(III)(CN)4], Tl(I)2C2O4, and (CONH2)2, have been obtained as products of the redox reactions in the system.

Journal Article↗
PubMed2005

[Second cancers in hematologic malignancies (epidemiologic observations from a 20-year period)].

INTRODUCTION: The incidence of malignant tumours have increased steadily worldwide. Prior reports indicate that patients with some hematologic malignancies (for example chronic lymphocytic leukemia, non-Hodgkin's lymphoma) may be at increased risk of second neoplasms. AIM: The aim of the authors was to explore the possible association between hematologic malignancies and subsequent solid tumours. PATIENTS, METHODS: Between January 1, 1983 and December 31, 2002, in the county of Szabolcs-Szatmár-Bereg 151 cases with both malignant hematologic diseases and cancers were registered by the authors. In their 60 patients (50 with lymphoid and 10 with myeloid malignancies) the first tumour was the hematologic malignancy. Among these cases the number of second cancers was 64. RESULTS: The most common kind of second tumours was lung cancer. There was a significant connection between lymphoid malignancies and second cancers as compared to myeloid malignancies and subsequent cancers (p < 0.05). CONCLUSIONS: Analysing the epidemiologic data the authors established the following conclusions: the association of second cancers with hematologic malignancies in most of the cases is not accidental. The age of patients with second cancers seemed to be not too important, but it was of crucial importance in patients with Hodgkin's disease and non-Hodgkin's lymphoma. The role of immunodeficiency in the development of second cancers may be important in patients with Hodgkin's disease, non-Hodgkin's lymphoma and chronic lymphocytic leukemia (the number of second cancers in their patients with multiple myeloma and hairy cell leukemia was too small do draw a conclusion).

Age Factors↗
PubMed2005

Signal transduction of erbB receptors in trastuzumab (Herceptin) sensitive and resistant cell lines: local stimulation using magnetic microspheres as assessed by quantitative digital microscopy.

BACKGROUND: ErbB2 (HER-2), a member of the epidermal growth factor (EGF) receptor family, is a class I transmembrane receptor tyrosine kinase. Although erbB2 has no known physiologic ligand, it can form complexes with other members of the family and undergo transactivation of its very potent kinase activity, thereby initiating downstream signaling and cell proliferation. ErbB2 is a frequent pathologic marker in ductal invasive breast carcinomas and is targeted by using a specific humanized monoclonal antibody, trastuzumab (Herceptin). The antibody is effective in only 20% to 50% of erbB2-positive tumors, and this resistance, as yet poorly understood, constitutes a major therapeutic challenge. METHODS: Magnetic microspheres coated with ligands or antibodies are widely used for separation of proteins and cells and allow localized, high intensity, and precisely timed stimulation of cells. We used EGF- and trastuzumab-covered paramagnetic microspheres, quantitative confocal laser scanning microscopy, and digital image processing to investigate the (trans)activation of and local signal propagation from erbB1 and erbB2 on trastuzumab sensitive and resistant carcinoma cell lines expressing these receptors at high levels. RESULTS: On A431 cells expressing high levels of endogenous erbB1 and transfected erbB2-mYFP (A4-erbB2-mYFP F4 cell line), EGF-coupled-microspheres activated erbB1 and transactivated erbB2-mYFP. In two other cell lines with comparable erbB2 expression but lower levels of erbB1, EGF microspheres transactivated erbB2 less efficiently. Trastuzumab in solution activated erbB2 on A4-erbB2-mYFP and the trastuzumab sensitive SKBR-3 cells, but only negligibly on the resistant JIMT-1 cells that showed a 10 times higher K(d) for the antibody. Nevertheless, pronounced erbB2 activation and tyrosine phosphorylation could be detected after stimulation with trastuzumab-coupled microspheres in all cell lines, although transactivation of erbB1 was negligible. Receptor phosphorylation was restricted to the immediate proximity of the microspheres, i.e., receptor clusters external to these locations remained inactive. CONCLUSION: ErbB1 ligand and erbB2 specific antibody attached to magnetic microspheres are efficient tools in assessing erbB activation, localized signal propagation, and erbB heterodimer formation. Trastuzumab coupled to microspheres is more efficient at accessing erbB2 and activating it than trastuzumab in solution.

Animals↗
PubMed2005

Reactive sulfur species: kinetics and mechanism of the oxidation of cystine by hypochlorous acid to give N,N'-dichlorocystine.

Cystine and HOCl (a neutrophil-derived oxidant) react to form an intermediate that has a half-life of ca. 5 min at pH 7.5. The intermediate subsequently decomposes to eventually yield a mixture of cystine, higher oxides of Cys, and other uncharacterized species. Spectral titrations, transitory (1)H NMR and UV-vis spectra, and the reaction properties of the intermediate are consistent with a formulation of N,N'-dichlorocystine {NDC = [-SCH(2)CH(NHCl)(CO(2)H)](2)}. The reaction of equimolar amounts of HOCl with cystine at pH 11.3 does not yield N-chlorocystine [NCC = (-O2C)(H3N+)CHCH(2)SSCH(2)CH(NHCl)(CO(2)H)] but rather a 1:1 mixture of NDC and cystine. This result could be explained by two mechanisms: rapid disproportionation of NCC to produce NDC and cystine or a faster reaction of the second equivalent of HOCl with NCC than the first equivalent of HOCl reacts with cystine. The latter mechanism is favored because of our observation by NMR spectroscopy that NDC decomposes via a species that we have assigned as NCC. Thus, disproportionation of NCC is apparently a relatively slow process. The rates of reaction of cystine(0) = [-SCH(2)CH(NH(3)(+))(CO(2)(-))](2) degrees , cystine(1-) = [((-)O(2)C)(H(2)N)CHCH(2)SSCH(2)CH(NH(3)(+))(CO(2)(-))](-), and cystine(2-) = [-SCH(2)CH(NH2)(CO2)(-))]2(2-) have been investigated, and it is clear that cystine(0) is unreactive, whereas cystine(2-) is about four times more reactive than cystine(1-). Accordingly, the following mechanism is proposed (constants for 5 degrees C): HOCl = H+ + OCl-, pK1 = 7.47; cystine(0) = cystine(1-) + H+, pK2 = 8.15; cystine(1-) = cystine(2-) + H+, pK3 = 9.00; cystine(1-) + HOCl --> NCC(1-) + H2O, k4 = 4.3(2) x 10(6) M(-1) s(-1); cystine(2-) + HOCl --> NCC(2)(-) + H2O, k5 = 1.6(2) x 10(7) M(-1) s(-1); NCC(1-) --> NCC(2-) + H+, k6 = fast; NCC(2-) + HOCl --> NDC(2-) + H2O, k7 = fast. At physiologic pH, the k4 pathway dominates. The generation of long-lived chloramine derivatives of cystine may have physiological consequences, since such compounds are known to react with nucleophiles via mechanisms that are also characteristic of HOCl, electrophilic transfer C+.

Cysteine↗
PubMed2004

[Novel factors playing a role in the pathomechanism of diffuse liver diseases: apoptosis and hepatic stem cells].

Liver diseases can basically be categorised into the forms diffuse and focal. In case of diffuse liver diseases the damages in general affect the whole of the liver, but the alterations are usually present in varying degrees and severity. Relatively stereotypical reactions develop in the liver tissues on the effect of various damaging factors. Some of these reactions and their pathogenic backgrounds are well known, while others have only recently come into focus, like apoptosis and the regeneration-proliferation related hepatic stem cells. The number of damaging effects are naturally much higher than the number of possible response reactions and as a consequence, in many cases the etiological factors can not unambiguously be identified from the tissue alterations. The basic reaction types of the liver can be divided into well defined categories; thus adaptive changes, degeneration and intracellular storage, cell death (necrosis/apoptosis), inflammation, fibrosis and structural reorganisation, as well as regeneration/proliferation. The picture of "classic necrosis" is well known; with the detection of cellular swelling, membrane damage. Apoptosis is characterised by cell shrinkage, nuclear and cytoplasmic disruption, while the cell membrane remains intact. Apoptosis occurs in several liver diseases, with a striking form of appearance being the Councilman-like body seen in viral hepatitis. Apoptosis may have role in the pathogenesis of cholestasis, biliary atresia, the "vanishing bile duct syndrome", and alcoholic liver injury. The regenerative ability of the liver is excellent. The process is influenced by several growth factors and cytokines. In the case of chronic liver damage, however, the regeneration equilibrium becomes upset and irregular. Studies on liver regeneration have led to the recognition of hepatic stem cells. These cells of "oval" morphologic appearance are built up of a primitive structure, making them suitable for this task. Ductular proliferation originating from hepatic stem cells can mostly be recognised in three disease groups: liver regeneration following massive or submassive liver necrosis, ductular proliferation without liver insufficiency, and tumorous liver diseases. At present it is still unclear whether the hepatocyte formation originating from haematopoetic stem cells is a rarely occurring accidental transformation, or rather, under appropriate circumstances, a greatly effective "third" protective system. If the latter is true, this can fundamentally change our view on the pathomechanism of liver diseases, making possible numerous novel therapeutic treatments.

Animals↗
PubMed2004

Kinetics and mechanism of platinum-thallium bond formation: the binuclear [(CN)5Pt-Tl(CN)](-) and the trinuclear [(CN)5Pt-Tl-Pt(CN)5](3-) complex.

Formation kinetics of the metal-metal bonded binuclear [(CN)(5)Pt-Tl(CN)](-) (1) and the trinuclear [(CN)(5)Pt-Tl-Pt(CN)(5)](3-) (2) complexes is studied, using the standard mix-and-measure spectrophotometric method. The overall reactions are Pt(CN)(4)(2-) + Tl(CN)(2)(+) <==> 1 and Pt(CN)(4)(2-) + [(CN)(5)Pt-Tl(CN)](-) <==> 2. The corresponding expressions for the pseudo-first-order rate constants are k(obs) = (k(1)[Tl(CN)(2)(+)] + k(-1))[Tl(CN)(2)(+)] (at Tl(CN)(2)(+) excess) and k(obs) = (k(2b)[Pt(CN)(4)(2-)] + k(-2b))[HCN] (at Pt(CN)(4)(2-) excess), and the computed parameters are k(1) = 1.04 +/- 0.02 M(-2) s(-1), k(-1) = k(1)/K(1) = 7 x 10(-5) M(-1) s(-1) and k(2b) = 0.45 +/- 0.04 M(-2) s(-1), K(2b) = 26 +/- 6 M(-1), k(-2b) = k(2b)/K(2b) = 0.017 M(-1) s(-1), respectively. Detailed kinetic models are proposed to rationalize the rate laws. Two important steps need to occur during the complex formation in both cases: (i) metal-metal bond formation and (ii) the coordination of the fifth cyanide to the platinum site in a nucleophilic addition. The main difference in the formation kinetics of the complexes is the nature of the cyanide donor in step ii. In the formation of [(CN)(5)Pt-Tl(CN)](-), Tl(CN)(2)(+) is the source of the cyanide ligand, while HCN is the cyanide donating agent in the formation of the trinuclear species. The combination of the results with previous data predict the following reactivity order for the nucleophilic agents: CN(-) > Tl(CN)(2)(+) > HCN.

Journal Article↗
PubMed2004

Effects of microelements on soil nematode assemblages seven years after contaminating an agricultural field.

Long-term effects of Cd, Cr, Cu, Se and Zn were studied 7 years after artificially contaminating plots of an agricultural field on a calcareous chernozem soil. Effects of three to four different contamination levels (originally 10, 30, 90 and 270 mg kg(-1)) were studied. Nematode density was significantly reduced by 90 and 270 mg kg(-1) Se as well as by 270 mg kg(-1) Cr, while 90 and 270 mg kg(-1) Se also reduced nematode generic richness. Maturity Index values (calculated for c-p 2-5 nematodes) consistently decreased with increasing Cr and Se concentration and to a lesser extent in Zn plots as well. Structure Index showed decreasing trends in increasing Cr, Se and (to a lesser extent) in Zn treatments, while in Cd it shows a moderate increase. Distribution of c-p groups was negatively affected by the increasing Cr and Se concentration, while in Zn plots, this decrease was not significant. Response of feeding groups to pollutions was similar to other parameters: Cr and Se caused significant changes toward the loss of variability. The proportion of the most sensitive omnivorous and predatory nematodes decreased clearly as a consequence of Cr and Se treatments. Zn pollution also resulted in a slight decrease in this group, while Cd caused an increase. Nematode diversity profiles showed a significant decrease in the plots of increased Cr and Se concentrations, while increased concentrations of Cu and Zn resulted in ambiguous effects. Besides providing evidence on the harmful effects of Cr and Se on a soil nematode assemblage, our results suggest that simultaneous analysis of Maturity Index, Structure Index and diversity profiles provide a promising tool in nematological indication of soil pollution.

Agriculture↗