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I Török

Publications and source records attributed to I Török.

At least 19 recordsLinked to original sources

Expression and distribution of carboxypeptidase B in the hippocampal subregions of normal and Alzheimer's disease brain.

Earlier neurochemical studies suggested that human brain carboxypeptidase B may play a significant role in the degradation of amyloid-beta1-42 in the brain. Using an immimohistochemical technique we report here on the neuronal expression and distribution of this enzyme in the segments (CA1a, CA1b and CA1c) of the CA1 subfield and in area CA4 of the hippocampus in normal and Alzheimer's disease brain samples. Its distribution was compared with the appearance of neurofibrillary tangles in the same brain sample. For immunohistochemical localization of carboxypeptidase B, a specific C14-module antibody was applied, together with the Gallyas silver impregnation technique for the demonstration of neurofibrillary tangles. The results revealed that, in the control samples, most of the immunoreactivity appeared in segment CA1a in the pyramidal cells, less in segment CA1b and least in segment CA1c. In the Alzheimer's disease samples, there was no particular immunostaining in the neurons, but, a large number of silver-impregnated degenerated neurons appeared. The results support the suggestion that carboxypeptidase B may play a significant role in elimination of the intracellular accumulation and toxicity of amyloid-beta in the human brain and thereby protect the neurons from degeneration.

Aged↗

Highly efficient phosphodiester hydrolysis promoted by a dinuclear copper(II) complex.

The interaction of Cu(II) with the ligand tdci (1,3,5-trideoxy-1,3,5-tris(dimethylamino)-cis-inositol) was studied both in the solid state and in solution. The complexes that were formed were also tested for phosphoesterase activity. The pentanuclear complex [Cu(5)(tdciH(-2))(tdci)(2)(OH)(2)(NO(3))(2)](NO(3))(4).6H(2)O consists of two dinuclear units and one trinuclear unit, having two shared copper(II) ions. The metal centers within the pentanuclear structure have three distinct coordination environments. All five copper(II) ions are linked by hydroxo/alkoxo bridges forming a Cu(5)O(6) cage. The Cu-Cu separations of the bridged centers are between 2.916 and 3.782 A, while those of the nonbridged metal ions are 5.455-5.712 A. The solution equilibria in the Cu(II)-tdci system proved to be extremely complicated. Depending on the pH and metal-to-ligand ratio, several differently deprotonated mono-, di-, and trinuclear complexes are formed. Their presence in solution was supported by mass, CW, and pulse EPR spectroscopic study, too. In these complexes, the metal ions are presumed to occupy tridentate [O(ax),N(eq),O(ax)] coordination sites and the O-donors of tdci may serve as bridging units between two metal ions. Additionally, deprotonation of the metal-bound water molecules may occur. The dinuclear Cu(2)LH(-3) species, formed around pH 8.5, provides outstanding rate acceleration for the hydrolysis of the activated phosphodiester bis(4-nitrophenyl)phosphate (BNPP). The second-order rate constant of BNPP hydrolysis promoted by the dinuclear complex (T = 298 K) is 0.95 M(-1) s(-1), which is ca. 47600-fold higher than that of the hydroxide ion catalyzed hydrolysis (k(OH)). Its activity is selective for the phosphodiester, and the hydrolysis was proved to be catalytic. The proposed bifunctional mechanism of the hydrolysis includes double Lewis acid activation and intramolecular nucleophilic catalysis.

Catalysis↗

[Doppler evaluation of the fetal arterial circulation: reference values of the Resistance Index and Pulsatility Index between the 28th and 41st weeks of gestation].

The authors established reference ranges for the Resistance Index and the Pulsatility Index of the umbilical artery, the fetal descending aorta and the middle cerebral artery in order to facilitate the uniform evaluation of the Doppler ultrasound examination in obstetrics. 164 patients with uncomplicated pregnancies between the 28th and 41st weeks of gestation were recruited for the longitudinal assessment of Doppler Resistance Indices and Pulsatility Indices in the fetal and umbilical arteries. Data were retrospectively analysed in order to establish the weekly mean values and standard deviations. The mean values of the indices in three periods (I.: 28-31, II.: 32-36, III.: 37-41 weeks) were compared. The normal haemodynamic resistance is reflected by the Doppler indices within the weekly mean +/- 2SD range. The results designate decreasing haemodynamic impedance in the umbilical and in the middle cerebral arteries while the resistance to the blood flow in the abdominal aorta is constant throughout the third trimester of gestation. The introduction and the clinical application of the reference values provides appropriate interpretation of the physiologic fetal blood flow patterns which is the prerequisite of the diagnostic accuracy of the Doppler ultrasound in obstetrics.

Aorta, Abdominal↗

Beta endorphin-like immunoreactivity in human aqueous humor and crystalline lens.

We measured the concentration of beta-endorphin (beta-End) in plasma, as well as in aqueous humor and crystalline lens removed during cataract surgery. beta-End was detected both in the aqueous humor and in the crystalline lens. The concentration of beta-End in the aqueous humor corresponded to almost the half of the plasma level (2.18 fmol/l and 4.55 fmol/l). Endogenous beta-End is presumed to enter the intraocular structures by passive diffusion.

Aged↗

Differential expression of two scribble isoforms during Drosophila embryogenesis.

The tumour suppressor gene scribble (scrib) is required for epithelial polarity and growth control in Drosophila. Here, we report the identification and embryonic expression pattern of two Scrib protein isoforms resulting from alternative splicing during scrib transcription. Both proteins are first ubiquitously expressed during early embryogenesis. Then, during morphogenesis each Scrib protein displays a specific pattern of expression in the central and peripheral nervous systems, CNS and PNS, respectively. During germ band extension, the expression of the longer form Scrib1 occurs predominantly in the neuroblasts derived from the neuro-ectoderm and becomes later restricted to CNS neurones as well as to the pole cells in the gonads. By contrast, the shorter form Scrib2 is strongly expressed in the PNS and a subset of CNS neurones.

Alternative Splicing↗

[Quo vadis, Pharmacopoeia Hungarica?].

The authors give an overview on the present role of the 7th Edition of the Hungarian Pharmacopoeia in the assurance of the good quality of medicines in Hungary. The reasons for the more and more limited applicability of the pharmacopoeia conflicting with its legal validity are shown for the most important groups of medicines. The authors, members of the presidium of the Hungarian Pharmacopoeia Commission, outline the future face and the timing of the publication of the 8th edition of the Hungarian Pharmacopoeia, which is intended to consist of the translations of the general chapters and monographs of the 3rd and 4th Editions of European Pharmacopoeia as well as of the so called national volume with monographs not included in the EP but harmonized with its general chapters. The impact of the new pharmacopoeia on the different fields of pharmacy and the necessary measures to be taken to make the switch-over from Ph. Hg. VII to Ph. Hg. VIII as smooth as possible are also summarised in the paper.

Europe↗

[Chromatographic methods in the European Pharmacopoeia].

A brief review is presented on the chromatographic separation techniques used in the European Pharmacopoeia (Ph.Eur.). The corresponding general chapters and the application of each technique in the individual monographs are covered. Special attention is paid to the discussion of the efforts of the Ph.Eur. aiming at the improvement of the reproducibility and reliability of the chromatographic methods in the monographs. In addition to showing the present policy of Ph.Eur. in the application of chromatographic techniques for different analytical purposes the paper also gives an overview on the changes to be expected in the near future.

Chromatography↗

[Does medicine lose its value near the expiration date?].

This is the question raised to the pharmacists by the patients very often. Medicines, being usually not selected by the customers but prescribed for the patients by their physicians are of a special sort of merchandise. As their efficacy is affected even by psychological factors it is necessary to emphasise that the quality and efficacy of medicines are shown to be constant by the date of expiry. In marketing authorization procedure not only the efficacy and safety but also the quality of the medicines are assessed and a special attention is paid to the chemical, physico-chemical and microbiological stability of the products. Detailed documentation on stability together with the good manufacturing practice of the pharmaceutical factories inspected regularly by the authorities and the system of post marketing surveillance assure that medicines do not loose their good quality and consequently their efficacy and safety by the expiry date stated on the label.

Drug Prescriptions↗

[Electroanalytical methods in the European pharmacopoeia].

A brief survey on the electroanalytical test methods applied by the European Pharmacopoeia is presented by the authors. The frequency of the use of electrochemical tests and the main fields of their application in the monographs together with the trends of development are discussed. Paying a special attention to the measures taken by the pharmacopoeia to reduce the systematic and random error in each type of measurements, the authors are analysing the content and characteristics of texts describing the electrochemical methods. System suitability tests included in the different procedures and their efficacy in ensuring the criteria established in the validation studies carried out during elaboration of the test methods are also shown.

Electrochemistry↗

Vitamin D receptor gene BsmI polymorphism correlates with erbB-2/HER-2 expression in human rectal cancer.

Apart from the regulation of calcium metabolism, 1, 25-dihydroxyvitamin D(3) plays an essential role in cell proliferation and differentiation in several tissues. The vitamin D receptor (VDR) gene shows polymorphisms in humans that appear to be clinically significant in some pathological conditions. In the present study, the BsmI polymorphism of the VDR gene was studied in 59 Caucasian patients with rectal cancer (mean follow-up: 48 months). The relationship between VDR genotypes and the expression of oncogenes as well as their influence on survival were also investigated. VDR polymorphism was examined in tumor and normal mucosa cells by PCR technique. The expression of erbB-2/HER-2, p53, ras and epidermal growth factor receptor (EGFR) was also detected by immunohistochemistry and protein blotting. The presence of the VDR B allele significantly correlated with the overexpression of the erbB-2 oncogene. There was no difference in the VDR genotype between cancer and normal mucosal cells. Coexpression of erbB-2, pan-ras, p53 and EGFR internal and external domains was significantly higher in cancer cells than in normal mucosa. There was no significant correlation between VDR genotypes and age, gender, tumor infiltration depth, number and site of lymph node metastases and lymphatic or blood vessel infiltration. The VDR genotype alone did not influence survival. Overexpression of erbB-2 and EGFR was associated with a poor prognosis. In patients expressing only one oncogene in cancer cells, the presence of the VDR B allele showed a tendency to a poor prognosis. In conclusion, VDR gene BsmI polymorphism might affect the development and prognosis of rectal cancer by influencing erbB-2 oncogene expression.

Adult↗

Structural and functional characterization of the Drosophila glycogen phosphorylase gene.

We identified a P element insertional mutant of the Drosophila glycogen phosphorylase (DGPH) gene. Glycogen phosphorylase protein concentration and enzyme activity are decreased while glycogen content is increased in flies homozygous for the mutant allele. The DGPH gene has been cloned and sequenced; its open reading frame codes for a protein of 844 amino acids with a predicted molecular mass of 97 kDa. Comparison of the conceptual amino acid sequence of the Drosophila glycogen phosphorylase with glycogen phosphorylase sequences from other organisms shows a high degree of homology to mammalian enzymes. All the residues of the allosteric effector binding sites, the active site, and the site of phosphorylation are exactly conserved, but some of the residues of the glycogen storage site are not.

Amino Acid Sequence↗

Down-regulation of RpS21, a putative translation initiation factor interacting with P40, produces viable minute imagos and larval lethality with overgrown hematopoietic organs and imaginal discs.

Down-regulation of the Drosophila ribosomal protein S21 gene (rpS21) causes a dominant weak Minute phenotype and recessively produces massive hyperplasia of the hematopoietic organs and moderate overgrowth of the imaginal discs during larval development. Here, we show that the S21 protein (RpS21) is bound to native 40S ribosomal subunits in a salt-labile association and is absent from polysomes, indicating that it acts as a translation initiation factor rather than as a core ribosomal protein. RpS21 can interact strongly with P40, a ribosomal peripheral protein encoded by the stubarista (sta) gene. Genetic studies reveal that P40 underexpression drastically enhances imaginal disc overgrowth in rpS21-deficient larvae, whereas viable combinations between rpS21 and sta affect the morphology of bristles, antennae, and aristae. These data demonstrate a strong interaction between components of the translation machinery and showed that their underexpression impairs the control of cell proliferation in both hematopoietic organs and imaginal discs.

Amino Acid Sequence↗

The congested-like tracheae gene of Drosophila melanogaster encodes a member of the mitochondrial carrier family required for gas-filling of the tracheal system and expansion of the wings after eclosion.

A recessive semi-lethal mutation resulting from the insertion of a P-lacW transposon at the cytological position 23A on the polytene chromosomes of Drosophila melanogaster was found to affect the unfolding and expansion of the wings resulting in a loss of venation and a marked decrease in their size. Lethality was polyphasic with numerous animals dying during early larval development and displaying apparently collapsed tracheal trees. The gene was therefore designated as congested-like tracheae, or colt. The colt mutation resulted from the insertion of a P-lacW transposon within the coding region of a 1.4-kb transcript. Wild-type function was restored by inducing a precise excision of the P-lacW transposon, while a deletion of the colt locus, produced by imprecise excision of the P element, showed a phenotype similar to that of the original P insert. The colt gene consists of a single exon and encodes a protein of 306 amino acids made of three tandem repeats, each characterized by two predicted transmembrane segments and a loop domain. The COLT protein shares extensive homology with proteins in the mitochondrial carrier family and particularly with the DIF-1 protein of Caenorhabditis elegans, which has been shown to be maternally required for embryonic tissue differentiation. Our analysis revealed that zygotic colt function is dispensable for normal embryonic morphogenesis but is required for gas-filling of the tracheal system at hatching time of the embryo and for normal epithelial morphogenesis of the wings.

Amino Acid Sequence↗

The DnaJ60 gene of Drosophila melanogaster encodes a new member of the DnaJ family of proteins.

In eukaryotes the DnaJ homolog constitute a family of proteins with diverse functions which all appear to involve the chaperone activity of Hsp70. Here, we report the molecular characterization of DnaJ60, a gene located at 60C on the right arm of the second chromosome of Drosophila melanogaster and encoding a putative protein of 217 amino acids with a molecular mass of 27.7-kDa and a pl of 10.5. The N-terminal region of the DnaJ60 protein displays a significant sequence similarity with the J domain of DnaJ proteins and contains a centrally located hydrophobic segment suggesting the occurrence of a membrane spanning domain. Northern blot analysis detected a 0.75-kb transcript which is weakly expressed in embryos, larvae and females but intensively expressed in adult males. In situ localization revealed that the DnaJ60 transcript is highly expressed in male testes and the ejaculary bulb but at an undetectable level in ovaries suggesting that the DnaJ60 protein may play an important function during spermatogenesis and/or in the male genital tract.

Amino Acid Sequence↗

[Chromatographic determination of novamidazofen in pharmaceutical preparations].

Novamidazofen (metamizol) has been used again as antipyretic and antirheumatic also in abroad recently. In aqueous solutions, such as injections, hydrolysis takes place in its formaldehyde sulfoxylate side chain resulting in an equilibrium mixture of novamidazofen and nor-amidazofen. A high-performance liquid chromatographic method was developed to study the hydrolysis and for the selective and accurate determination of the two components. UV detection at 242 nm wavelength, where the absorbance of novamidazofen and nor-amidazofen were identical, was applied. The rate constants k1 and k3 of the opposite direction reactions as well as K = k1 k3(-1), the hydrolytic equilibrium constant were determined. In aqueous solution, at I-->0 ionic strength and 25 degrees C pK = 3.52 +/- 0.12; 10(4) k1 = 1.74 (+/- 0.25) min-1, P = 0.95. Addition of methanol to the system decreased both the rate and equilibrium constants of the hydrolysis. For the quantitation of novamidazofen Nucleosil C18 column and 20 mmol dm-3 natrium sulphate in methanol-water 40 + 60 V + V eluent were used. The calibration curve was linear in the 20 to 1000 ng range. This method is suitable also for the detection of other, mostly oxidised impurities. A thin-layer chromatographic procedure was also developed on silica GF254 applying acetone-water-ether 30 + 40 + 5 V + V + V eluent. After extraction with chloroform, the oxidised decomposition products can be detected also in injections allowed to stand for a few minutes in an open vessel. The densitometric version of the TLC method was also developed but its precision was lower than that of the HPLC.

Anti-Inflammatory Agents, Non-Steroidal↗

[Stability of rifampicin in eyedrops].

The best composition of rifampicin eye-drops for extemporaneous preparation in pharmacies was developed by the authors. The stability of the eye-drops has been studied and storage condition and shelf-life were determined. The preparation, may be stored at minus 12 degrees C for one month and may be subsequently used when stored between 2 and 8 degrees C after the first opening for five days. Rifampicin and its degradation products have been separated by TLC using silicagel layer and chloroform-methanol (42 : 58) eluent. After separation of rifampicin and its degradation products their quantity have been determined by densitometry at 475 wavelength (540 nm for rifampicin quinone). This rifampicin eye-drops have been recommended for inclusion into the 7th Edition of the Official Model Prescriptions (Formulae Normales).

Chromatography, Thin Layer↗

The overgrown hematopoietic organs-31 tumor suppressor gene of Drosophila encodes an Importin-like protein accumulating in the nucleus at the onset of mitosis.

The tumor suppressor gene overgrown hematopoietic organs-31 (oho31) of Drosophila encodes a protein with extensive homology to the Importin protein of Xenopus (50% identity), the related yeast SRP1 protein, and the mammalian hSRP1 and RCH1 proteins. A strong reduction in the expression of oho31 by a P element inserted in the 5' untranslated region of the oho31 transcript or a complete inactivation of oho31 by imprecise P element excision leads to malignant development of the hematopoietic organs and the genital disc, as shown by their growth autonomy in transplantation assays. We have cloned the oho31 gene of Drosophila melanogaster and determined its nucleotide sequence. The gene encodes a phosphoprotein of 522 amino acids made of three domains: a central hydrophobic domain of eight repeats of 42-44 amino acids each, displaying similarity to the arm motif found in junctional and nucleopore complex proteins, and flanked by two hydrophilic NH2- and COOH-terminal domains. Immunostaining revealed that the OHO31 protein is supplied maternally and rapidly degraded during the first 13 nuclear divisions. Thereafter, the OHO31 protein is predominantly expressed, albeit at reduced levels, in proliferating tissues. During the interphase of early embryonic cell cycles, the OHO31 protein is present in the cytoplasm and massively accumulates in the nucleus at the onset of mitosis in late interphase and prophase. The nuclear import of OHO31 is, however, less pronounced during later developmental stages. These results suggest that, similar to Importin, OHO31 may act as a cytosolic factor in nuclear transport. Moreover, the cell cycle-dependent accumulation of OHO31 in the nucleus indicates that this protein may be required for critical nuclear reactions occurring at the onset of mitosis.

Amino Acid Sequence↗