bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Urinary Neopterin Excretion in Vaccinated Adults
Authors: Giovannoni Gavin , Bell Joan , Feldmann Marc , Thompson Edward J. 
Published: March 2013

Summary Serial urinary neopterin :creatinine ratios of 58 healthy adult sub jects were measured from 2 days prior to and up to 12 days post vaccination. An increase in the urinary neopterin of at least twice the baseline was detected in 24/ 46 subjects who received either a Mantoux skin test or a live viral vaccine (cell mediated immune group, median average increase above baseline = 206%(interquartile range 150-338% ), and 'in 5/12 who received non-live vaccines known to stimulate mainly humoral immunity (humoral immune group, median average increase above baseline = 165%((interquartile range 142-412%) ). The peaks in the urinary neopterin in the cell mediated group occurred between days 5 and 10 post-vaccination, with the mode on day 5. In contrast the 5 subjects in the humoral immune group all developed their peaks on day 7 or 8 . Three of these subjects received an influenza vaccine, one a typhoid vaccine and one a tetanus toxoid. No association was found between local or systemic side-effects of vaccination and raised urinary neopterin . In conclusion, the monitoring of urinary neopterin excretion in adults is sensitive enough to detect an immunological response to vaccination with immunogens that induce either cell mediated or humoral immune responses.
Pteridines CVIII Reactions of 6, 7-Dichloro-I, 3-dimethyllumazine with Sulfur-Nucleophiles
Authors: Abou-Hadeed Khaled , Pfleiderer Wolfgang 
Published: March 2013

Summary
6,7-Dichloro-1,3-dimethyllumazine (1) and various 6-chloro-7-O-, S- and N-subst.-1,3-dimethyllumazines (2-7) react under relatively mild reaction condiditions with S-nucleophiles to the corresponding 6-mercapto derivatives 8-16. Treatment of 1 with sodium benzylmercaptide at room temperature led to di-( 6- chloro-1,3-dimethyllumazine-7-yl)sulfide (17) whereas thiourea caused transformation to the corresponding 7,7-disulfide 18. 7-Mercapto-1,3-dimethyl-6(5H)lumazinethione (12) can be modified widely by alkylations to open-chain (21-23, 27-29) or cyclic 6,7-bis-alkylthio derivatives (24-26) and acylations with phosgene and thiophosgene, respectivly, gave the derivatives 36 and 37 of the new 1 ,3-dithiolo[ 4,5-g]pteridine ring system. Ribosylation of 12 afforded a 6,7-bis-S-riboside (40) in high yield.
In vitro Mutagenesis of Human Dihydropteridine Reductase at the Active Site and at Altered Sites Found in the Reductases of Deficient Children
Authors: Zhang Hong-Ping , Yang Nan , Armarego Wilfred L. F. 
Published: March 2013

Summary
A general procedure for in vitro site-directed mutagenesis of the wild-type dihydropteridine reductase gene has been used successfully to make eight mutant proteins. Five mutations were at the active site, viz Tyrl50His, Tyrl50Ser, Tyrl50Phe, Tyr150Glu and Tyrl50Lys. The proteins were expressed as glutathione S-transferase fusion proteins from which the unconjugated reductases were obtained by thrombin cleavage. The kinetic parameters of the conjugated and unconjugated reductases were measured using natural quinonoid R-7,8(6H)-dihydrobiopterin and non-natural quinonoid RS-6-methyl-7,8(6H)-dihydropterin and NADH. The kcat (maximum velocity at saturating concentrations of substrates) and kcatl Km (first order rate constant at low concentration of substrates) values show that the phenolic OH of Tyr 150 was the most likely proton source to complete the hydride reduction of the quinonoid pterin cofactor. However in the absence of a proton source at residue 150, measurable enzyme activities were observed indicating that a proton was relayed via a water molecule(s) from some neighbouring acidic amino acid residue. Three mutant dihydropteridine reductases, which were found in defective children, have been similarly attempted, viz GlylSlSer, Gly23Asp and a threonine insertion at position 123. The enzyme activities of the first two mutant reductases were consistent with the severity of the disease. The unconjugated reductase from the third mutation could not be obtained due to proteolysis but the fusion protein was enzymically active.
Varying Folate Pattern in Different Strains of Mice Fed Coconut Oil and Sesame Seed Oil Diet
Authors: Kulkarni Medha V. , Nair C.P. Parameswaran , Viswanathan Gomathy 
Published: March 2013

Summary
The effect of coconut oil feeding with and without cholesterol on folate metabolism in the two strains of mice, C57BL/6 and AKR have been studied. Liver total folate levels are higher in AKR mice. Coconut oil feeding markedly decreased the ratio of nonmethyl/methyl folates in C57BL/6 strain but not in AKR. Cholesterol supplementation to the coconut oil diet increased the percentage of monoglutamyl folates at the expense of polyglutamyl folates in both strains. Only C57BL/6 strain showed growth retardation on coconut oil feeding. The differences in hepatic folate metabolism between the two strains could possibly have an important role in determining their differences in susceptibility to diet induced atherosclerosis.
5,6,7,8-tetrahydroneopterin (NH4) Acts like an Endogenous Superoxide Dismutase
Authors: Sawada Suguru , Morimoto Takeshi , Kito Tsuyoshi , Taguchi Osamu , Yasumura Mikio , Hirose Hajime 
Published: March 2013

Summary
The protective effect of 5,6,7,8-tetrahydroneopterin (NH.) against radiation injury in mice was studied. (C57BL/6x A/J)F1 mice received whole body irradiation with a single fatal dose of 8.0 Gy X-ray. NH4 was injected intraperitoneally into irradiated mice at various protocols. NH. was significantly effective to prolong the survival of the irradiated mice. The most effective protocol of NH4 administration was 3 times injections (10 minutes before and after irradiation and additional one 12 hours after that.) with a dose of 30 mg/kg body weight for each. Some mice that received such treatment survived more than 30 days after irradiation. In conclusion, these results indicate that NH4 has an inhibitory potential on radiation injury as an endogenous superoxide dismutase like substance.
A Comparison of Sepiapterin and Tetrahydrobiopterin Uptake by BRL2H3 Cells
Authors: Yamamoto Kazumasa , Nagano Mutsumi , Nakanishi Nobuo , Hasegawa Hiroyuki 
Published: March 2013

Summary
Cellular uptake of sepiapterin and tetrahydrobiopterin was compared quantitatively with RBL2H3 cells in culture. RBL2H3 is a mast cell line and has the ability to synthesize serotonin. Sepiapterin was incorporated and converted into tetrahydrobiopterin in the cell. The incorporation of sepiapterin was about 10 times faster than tetrahydrobiopterin. A low concentration of tetrahydrobiopterin was incorporated in a saturable manner up to about 10 μM, and it was superimposed upon a linearly concentration- dependent process. Overnight treatment with DAHP depleted endogenous tetrahydrobiopterin. The DAHP treated cells took up tetrahydrobiopterin faster than untreated cells.
Effects of Neopterin on Focal Cerebral Ischemia In Rats
Authors: Arai Toshiyuki , Ishii Hisanari , Mori Hiroko , Mori Kenjiro , Kojima Shuji 
Published: March 2013

Summary
We examined the effects of neopterin on focal cerebral ischemia induced by transient (2 h) occlusion of the middle cerebral artery (MCA) in rats. Neopterin was administered 10 min before reperfusion (3 mg/kg i.p). The ischemic damage was evaluated one week after the MCA occlusion by magnetic resonance imaging (MRI) and by the immunohistochemical reaction for microtubule-associated protein 2 (MAP2). The ischemic lesion detected by MRI was significantly smaller in the neopterin-treated group than in the non-treated group (n=4 in each group, p<0.05). However, the ischemic neuronal damage determined by MAP2 in the neopterintreated group was not significantly different from that in the non-treated group. Since MRI is thought to reflect the distribution of not only neurons but also glial cells, these results may indicate the effects of neopterin on the glial reaction in focal cerebral ischemia.
Urinary and Serum Pteridines in Liver Diseases
Authors: Mazda Toshio , Iino Teruhiko , Tsusué Motoo 
Published: March 2013

Summary
The aim of this mini-review is to show the usefulness of pteridines as clinical markers. We assayed urinary neopterin and xanthopterin levels in liver disease. Total pterins were oxidized by active carbon to yield xanthopterin. Urinary neopterin levels were elevated in patients with chronic active hepatitis and in those with chronic persistent hepatitis but not in patients with alcohol-induced liver disease or in those with non-alcoholic fatty liver. Urinary xanthopterin levels were elevated in chronic active hepatitis and alcohol- induced liver disease, but not in chronic persistent hepatitis and non-alcoholic fatty liver. Urinary neopterin levels were high in infectious diseases involving activated cell-mediated immunity, and increased urinary xanthopterin reflects liver-cell damage. We also compared plasma neopterin values in anti-hepatits C virus antibody (anti-HCV) -positive or - negative donors with elevated alanine aminotransferase (ALT). Plasma neopterin values of anti-HCV-negative donors with elevated ALT were the same as those of healthy groups. These results show that the ALT elevation in anti-HCV-negative donors is attributable mainly to steatosis due to excess body weight and/or alcohol consumption, rather than viral infection. During the course of these studies, we were also able to identify esophageal carcinoma in the very early stage by measuring urinary pteridine levels. Our results indicate that pteridines are clinically useful indicators. In particular, neopterin may be used as a means of screening for unknown viral infection.
Regioselective Arylation of 1,3-Dimethyllumazine and Its 5-Oxide by Diazonium Salts
Authors: Sugimoto Takashi , Seo Chihiro , Murata Shizuaki , Pfleiderer Wolfgang 
Published: March 2013

Summary A new method to introduce an aryl group directly into the pteridine nucleus by the action of arene diazonium salt in an aqueous alkaline solution is described. 1,3-Dimethyllumazine and benzene diazonium chloride reacts in an aqueous solution at pH 8-9 to give 7 -phenyl-1 ,3-dimethyllumazine together with a little of 6-phenyi-1 ,3-dimethyllumazine. The analogous reactions of 1,3-dimethyllumazine with 4-methyl-, 4-methm.),-, 4-chloro-, and 3-chlorobenzene diazonium chlorides give the corresponding 7-aryl-1,3-dimethyllumazines as major products together with a little of 6-aryl-1,3-dimethyllumazines. Reactions of 1,3-dimethyllumazine 5-oxide with arene diazonium salts under the same conditions exclusively afford the corresponding 6-aryl-1,3-dimethyllumazine 5-oxides which are easily converted to 6-aryl-1,3-dimethyllumazine by the action of tributylphosphine. Mechanisms concerning regioselectivities are investigated by using molecular orbital calculations.
Influence of Three Different Diet Modes Combined with Exercise Loads on Urinary and Plasma Neopterin Concentrations: A Longitudinal Study
Authors: Lamprecht Manfred , Mlekusch Walter , Vrecko Karoline , Reibnegger Gilbert 
Published: March 2013

Summary During six months, we studied the influence of three extremely different diet modes (normal diet, carbohydrate- rich diet, fat-rich diet) combined with three defined exercise loads (step test, endurance test fo r 30 minutes, endurance test for 90 minutes) on daily urinary neopterin concentrations of one voluntary subject. Furthermore, plasma neopterin was determmed before, during and after each exercist: load. Each diet period lasted for 28 days and was performed twice : once without, and once with extra supplementation of antioxidants. Urinary neopterin concentrations showed a markedly high daily fluctuation, and there were three occasions with infectious complications which were accompanied by significantly raised uiinary neopterin. Howevt:r, when comparing neopterin levels grouped according to diet mode, absolutely no difference was found. Similarly, neither had supplementation an influence on neopterin, nor could coherent effects of the exercise loads on neopterin be detected. While plasma neopterin concentrations were significantly higher during exercise loads than before and after, the increase was small (about I nmol/l) and might have been due to slight alterations of renal function and/or hemodynamics during the physical exercise . Our study supports the robustness of the immune activation marker neopterin since no influences of these truly extreme diet modes on urinary and plasma neopterin could be detected, and exercise loads had no appreciable influence on urinary as well as plasma neopterin concentrations.
Release of Neopterin, PMN Elastase and Terminal Complement Complexes by Orthotopic Liver Transplantation with and without the Use of Veno-venous Bypass
Authors: Tomasdottir H. , Rønholm E. , Bengtson JP , Bengtsson A. 
Published: March 2013

Summary Aim: The aim of the study was to determine whether orthotopic liver transplantation leads to the activation of macrophages, neutrophils and complement. Patients and methods: Twenty-four patients undergoing orthotopic liver transplantation were studied. 12 were operated on with and 12 without the use of a veno-venous bypass. Blood samples for neopterin, PMN elastase and terminal complement complex (SC5b-9) determinations were drawn preoperatively, 1 minute before perfusion of the grafted liver and 2-5 and 30-60 minutes after the start of perfusion of the grafted liver. Comparisons were made between patients with or withour a veno-venous bypass and with or without postreperfusion syndrome (PRS) . PRS was defined as hypotension with ≥30% reduction of systemic mean arterial blood pressure during at least 1 minute after reperfusion of the grafted liver. Results: Release of neopterin was observed 2-5 and 30-60 minutes after the start of perfusion of the grafted liver in patients operated upon with and without the use of a veno-venous bypass. There were no significant differences in neopterin concentration between patients developing PRS and those without circulatory instability. Increased PMN elastase and SC5b-9 concentrations (p<0.05) were found 2-5 and 30-60 minutes after the start of reperfusion in both patients operated upon with and without a veno-venous bypass. The plasma concentrations of neopterin, PMN elastase and SC5b-9 were higher in patients with PRS compared with those without (p<0.05, respectively). Comments: This study indicates that orthotopic liver transplantation leads to the activation of macrophages, neutrophils and the complement cascade. There is no major difference regarding the activation between patients operated upon with and without the use of a veno-venous bypass.
Purification and Characterization of Sepiapterin Deaminase from the Silkworm, Bombyx mori
Authors: Sawada Hiroshi , Kanekatsu Motoki , Nakagoshi Motoko , Dohke Kenjiro , Iino Teruhiko , Takikawa Shin-Ichiro 
Published: March 2013

Summary Sepiapterin deaminase has been purified approximately 6,000-told from the larval integument of the lemon mutant of the silkworm by several column chromatographic procedures. Sepiapterin and isosepiapterin were active substrates among various pteridines tested. The molecular mass of this enzyme was estimated to be 74 kDa by SDS-PAGE and 70 kDa by gel filtration, suggesting that the native form of the enzyme is monomeric protein . All silkworm strains, to the best of our knowledge, had an activity of the enzyme and the enzyme was widely distributed in the larval tissues. Sepiapterin deaminase may have an important function on the silkworm.
Altered Tryptophan and Neopterin Metabolism In Cancer Patients
Authors: Iwagaki Hiromi , Hizuta Akio , Nitta Yasuki , Tanaka Noriaki 
Published: March 2013

Summary Plasma 5-hydroxytryptamine (serotonin), tryptophan and neopterin levels were measured in patients with depressive cancer cachexia and in healthy controls during the same time period. Patients with advanced cancers had significantly raised neopterin, a marker of endogenous gamma-interferon (IFN-γ) production, but decreased serotonin and tryptophan levels. IFN-γ induces a high level of indoleamine dioxvgenase (IDO), a tryptophan degrading enzyme, which in turn increases metabolism along the tryptophan- nicotinic acid pathway, resulting in decreased synthesis of serotonin. These results suggest that persistent immune activation occur in patients with cancer cachexia, resulting in disorders involving tryptophan metabolism.
Effects of Tetrahydrobiopterin (BH4) on S-Nitroso-N-acetyl-D,Lpenicillamine (SNAP)-Induced HL-60 Cell Death
Authors: Kojima Shuji 
Published: March 2013

Summary First, we examined the effects of various chemical NO-donors on the cell damage in HL-60 cells. The most potent of these was S-nitroso-N-acetyl- penicillamine (SNAP). The effect of 5,6,7,8-tetrahydrobiopterin (BH4) on HL-60 cell damage induced by SNAP was investigated. Analysis of electrophoresis of DNA fragmentation induced by SNAP indicated that the cell damage was caused via apoptosis. This phenomenon was observed as early as 5 hr after the treatment with 500 mM SNAP. Apoptosis observed at an early time, 5 hr post-treatment with SNAP, was inhibited by BH4 . However, BH4 significantly increased cell death observed at a later time, 20 hr after the treatment. These results suggest that BH4 may be involved in modulating the cytotoxicity, including cell death, mediated by NO.
Influences of Catecholamine Contents on Tetrahydrobiopterin Metabolism
Authors: Kuzuya Hiroshi , Sakamoto Hideo , Fujita Ko 
Published: March 2013

Summary The influence of changes in catecholamine metabolism on tetrahydrobiopterin biosynthesis was investigated in cultured rat pheochromocytoma PC12 cells. The increase in the cellular dopamine content after treatment with the MAO-COMT inhibitor or dopamine produced decreases in the GTP-cy-clohydrolase I (GTPCH-I) activity and total biopterin content. On the contrary, the catecholamine increase after treatment with nerve growth factor produced increases in the GTPCH -I activity and total biopterin content. On the other hand, the decrease in the dopamine content after tyrosine hydroxylase (TH) inhibitor treatment produced decreases in the GTPCH-I activity and total biopterin content, but the catecholamine decrease (the DOPA content increased about 3.4-fold) after aromatic L-amino acid decarboxylase inhibitor treatment produced a decrease in the GTPCH-I activity. These results suggest that an increase in dopamine content that is not directly related to the action of TH plays a role in down-regulation of tetrahydrobiopterin biosynthesis and that when the changes in catecholamine metabolism are strongly associated with the action of TH, tetrahydrobiopterin biosynthesis is regulated depending on the necessity for TH.
Neopterin, Serum Amyloid A, and Cytokine Monitoring After Renal Transplantation
Authors: Neumann M. Christine , Sprenger Hans , Grebe Scott O. , Gemsa Dietmar , Reibnegger Gilbert , Lange Harald , Müller Thomas F. 
Published: March 2013

Summary A reliable and early diagnosis of viral infections and rejection episodes is a major goal of immunologic monitoring in transplantation. Soluble markers like the cytokines, neopterin or serum amyloid A are frequently recommended as diagnostic parameters. However they are not often used routinely in transplant medicine. The study investigates the diagnostic value of plasma (P), serum (S), and urine (U) levels of neopterin (S-/U-NEOP), serum amyloid A (SAA), tumor necrosis factor-α, (P-/U-TNF-α), soluble interleukin-2 receptor (P-/U -sIL-2R), and interleukin-6 (U -IL-6) in transplant monitoring and describes an approach for their use in the clinical routine decision making. In 29 renal transplant patients blood and urine samples were collected daily during the posttransplant course on ward. The cytokines were measured by ELISAs, neopterin by RIA, and SAA by immunonephelometry. Descriptive statistics, sensitivity and specificity, day of first significant parameter increase/decrease, receiver operating characteristic curves, and post-test probabilities were calculated for each parameter. 12 acute rejection episodes were diagnosed. As rejection markers, S-NEOP and P-TNF-α had the highest sensitivity, U-IL-6 the highest specificity. 8 viral infections occurred. U-NEOP showed values higher than 1000 μmol/moICrea. It did not exceed this threshold in case of rejection episodes. SAA and U-IL-6 showed peak. levels during rejections but not during episodes of viral infections. Using the calculated likelihood ratio formulas the probability for the occurrence of an acute rejection could be estimated for the individual, daily parameter measurement. Adding the physician IS rating for rejection posttest probabilities were computed. Immunologic monitoring is possible in transplant medicine. Using daily measurements of serum amyloid A and neopterin facilitates the differential diagnosis of acute rejection episodes and viral infections. The likelihood ratio approach permits an application of the parameter monitoring in the clinical routine.
Pteridines CIX
Authors: Abou-Hadeed Khaled , Pfleiderer Wolfgang 
Published: March 2013

Summary A simple direct method for the synthesis of lumazine-6,7-diamines (9, 25-27) from uracil-5,6-diamines (10-13) and methyl cyanoformimidate (24) was found. Various nucleophilic displacement reactions were performed with 7-chloro-1,3-dimethyllumazine-6-amine (17) leading to new 6,7-disubstituted 1,3- dimethyllumazine derivatives (18-23).
Inhibition of Mycelial Growth by Methotrexate in Neurospora crassa Wild Type and Mutants Deficient in Folylpolyglutamate Synthase
Authors: Wrishko Rebecca E. , Cossins Edwin A. 
Published: March 2013

Summary In mammalian cells, folylpolyglutamate synthase (FPGS) catalyzes the polyglutamylation of methotrexate (MTX), a reaction that significantly enhances the cellular retention and cytotoxicity of this antifolate. In contrast, MTX is a poor substrate for the cytosolic FPGS of Neurospora crassa. The present study has therefore examined the effect of MTX on growth of N. crassa wild type (FGSC 853 ) and two mutants (met-6, FGSC 1330 and mac, FGSC 3609) that have lesions affecting FPGS expression. Mycelial dry weights after growth in MTX-supplemented media, suggested that met-6 and mac were more sensitive to the antifolate than the wild type (WT). MTX concentrations resulting in 50% inhibition of growth (ICso values) were 5.5 11M, 6.0 11M and 87.5 11M for met-6, mac, and WT, respectively. When MTX treatment was followed by transfer to 50 11M folinic acid-supplemented media, growth of both mutants was enhanced by ca. 20% while that of WT increased by ca. 8%. [3H]-MTX pulse-chase experiments demonstrated that all three strains had limited or no ability to form polyglutamates (MTXGlun ) of the antifolate. In WT cultures, supplied with 1 I-tM [3H]-MTX for 24 hr and then grown in MTX-free media for another 24 hr, over 95% of the recovered label was in MTX; MTXGlu2 and MTXGlu3 accounting for only 2% and 1% respectively. MTXGlun derivatives were not detected in mac but low levels of MTXGlu2 were generated by met-6. In all three strains, the level of expression of dihydrofolate reductase (DHFR) was similar. DHFR was purified to apparent homogeneity (21.6 kDa) from extracts of each strain using a protocol of ammonium sulfate fractionation, gel filtration and Matrex Green A chromatography. It is concluded that in Neurospora, MTX polyglutamylation is not a major factor in the cytotoxicity of this antifolate.