bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and Structure of the Phosphonocarboxylic Acid H2O3PCH2‐NC5H9‐COOH·2H2O and the Manganese Phosphonocarboxylate Mn[O3PCH2‐N(H)C5H9‐COO]
Authors: Stock Norbert , Karaghiosoff K. , Bein T.
Published: October 2004

The phosphonocarboxylic acid H2O3PCH2‐NC5H9‐COOH·2H2O (1) was synthesized by a Mannich‐type reaction. Recrystallization from hydrochloric acid yields large single crystals (crystal data 1: monoclinic, P21/n, a = 6.4011(3), b = 25.633(2), c = 7.2496(4) Å, β = 95.473(7)°, V = 1184.1(2) Å3, Z = 4). In an aqueous solution two isomers of 1 were unambiguously detected by NMR‐spectroscopy. The reaction of 1 with manganese chloride under hydrothermal conditions at pH 5 yields the new manganese phosphonocarboxylate Mn[O3PCH2‐N(H)C5H9‐COO] (2) that was characterized by single crystal X‐ray diffraction (crystal data 2: monoclinic, P21/a, a = 10.2784(2), b = 9.0649(2), c = 11.0712(2) Å, β = 107.280(1)°, V = 984.97(3) Å3, Z = 4). In 1 zwitter‐ions HO3PCH2‐N(H)C5H9‐COOH and H2O molecules are interconnected by O‐H···O and N‐H···O hydrogen bonds to form a three‐dimensional network. In 2, corner‐linked MnO5 and PO3C polyhedra form four‐ and eight‐rings which are connected to a two‐dimensional net. The coordination of the carboxylate ions, which act as chelating ligands, leads to a pillared structure.
Darstellung und Charakterisierung der nanoskaligen Vb‐Metalloxide M2O5 (M = V, Nb, Ta)
Authors: Feldmann C.
Published: October 2004

Die Darstellung nanoskaliger Vb‐Metalloxide M2O5 (M = V, Nb, Ta) gelingt durch Polyol‐vermittelte Synthese. Diese erfolgt durch kontrollierte Hydrolyse der Alkoholate VO(i‐OC3H7)3, Nb(OC2H5)5 und Ta(OC2H5)5 in Diethylenglykol (DEG) bei 180 °C und liefert die Oxide in einem Größenbereich von etwa 10 bis 200 nm. Der monodisperse Habitus sowie das kolloidale Verhalten der nanoskaligen M2O5‐Partikel in DEG und Wasser belegen die oberflächenaktive Wirkung des Diethylenglykols hinsichtlich Partikelwachstum und Partikelagglomeration. Thermogravimetrische Daten und Untersuchungen zur B.E.T.‐Oberfläche lassen auf eine der Größenordnung nach monomolekulare Belegung der M2O5‐Partikeloberflächen mit DEG‐Molekülen schließen. Gemäß Elektronen‐ und Röntgenbeugungsbildern fallen die nanoskaligen Partikel nach der Synthese zunächst amorph an, durch eine moderate Temperaturbehandlung kann jedoch eine deutliche Erhöhung der Kristallinität erreicht werden.
[Me4N]5[WOS3(CuCl)3Cl]Cl2 ‐ a Cluster Compound with Alternating Anion Packing
Authors: Dilshad R. , Boller H. , Klepp K. O.
Published: October 2004

Orange‐yellow plate‐like crystals of the title compound were obtained from the reaction of [Me4N]2WO2S2 or [Me4N]2WOS3 with CuCl and [Me4N]Cl in MeCN solution. They are hexagonal, space group P63cm (No.185), with unit cell parameters a = 11.638(4) Å, c = 17.970(7) Å, Z = 2. The crystal structure was determined from single crystal X‐ray diffraction data (MoKα‐radiation) and refined to R = 0.049. The structure is characterized as an alternating packing of cubane‐like [WOS3(CuCl)3Cl]3‐ and Cl‐ anions.
Point Defects as Acid—Base Active Particles in Ionic Crystals
Authors: Maier Joachim
Published: October 2004

Point defects such as excess ions or ion vacancies (together with excess electrons and holes as the electronic excitations) enable the solid to react to outer chemical and electrical excitations. They are not only the mobile ionic constituents, they are also the relevantacid‐base activeparticles with respect to reactivity. It is in particular this latter aspect that is not adequately appreciated in the literature. A recently developed concept based on point defects [1] is able to provide an objective, testable and thermodynamically valuable ionotropic acid‐base concept for solids. The concept also allows one to unify bulk and surface acidity/basicity. These points are discussed in conjunction with the important role of point defects in reaction kinetics and catalysis.
Effect of stabilization of crude whale oil with tertiary butylhydroquinone and other antioxidants upon keeping quality of resultant deodorized oil. A feasibility study
Authors: Chahine M. H. , Macneill R. F.
Published: October 2004

Crude whale oil was stored under accelerated conditions for 146 days alone and in the presence of added antioxidants: 0.02% butylated hydroxyanisole, 3,5‐di‐t‐butyl‐4‐hydroxyanisole, propyl gallate, tertiary butylhydroquinone, TBHQ + 0.01% citric acid, and 0.01% citric acid. Inverse relationships were noted between peroxide values and oxidative stabilities and also between secondary oxidation products, measured by anisidine value, and oxidative stabilities at termination of the storage of antoxidant‐treated crudes. Tertiary butylhydroquinone was most effective, followed by butylated hydroxyanisole,3,5‐di‐t‐butyl‐4‐hydroxyanisole, and propyl gallate, in decreasing order, with respect to retardment of oxidative deterioration of stored crude whale oil. All antioxidant‐treated crudes were alkali refined and steam deodorized. Stability times of deodorized oils from crudes treated with butylated hydroxyanisole,3,5‐di‐t‐butyl‐4‐hydroxyanisole, propyl gallate and citric acid ranged from 13.5–18 days at 30 C. Deodorized oils from tertiary butylhydroquinone‐and tertiary butylhydroquinone‐citric acid‐treated crudes gave much longer stability times against oxidative deterioration at 30 C, viz. 49.5 and 56 days, respectively. The major factor that contributed to the improvement in oxidative stability and caused continued effectiveness of tertiary butylhydroquinone even after deodorization was the carry‐through of the antioxidant and its oxidation products from the crude into the deodorized oil. If tertiary butylhydroquinone‐stabilized crude oils are deodorized, the residual antioxidant and its oxidation products should be determined quantitatively by adequate analytical methods and be included as part of the food‐approved antioxidants in processed edible oils.
Linolenic acid artifacts from the deodorization of oils
Authors: Ackman R. G. , Hooper S. N. , Hooper D. L.
Published: October 2004

Gas liquid chromatography on polar open tubular columns of the methyl esters of fatty acids from vegetable oils shows that the linolenic acid in deodorized oils is accompanied by two major artifacts identified as cis‐9,cis‐12,trans‐15 and trans‐9,cis‐12,cis‐15 isomers. Physicochemical studies, isolation, and partial degradation steps showed two additional isomers with trans‐9,cis‐12,trans‐15 and cis‐9,trans‐12,cis‐15 structures. Gas liquid chromatography also showed that linoleic acid was accompanied by the trans‐9,cis‐12 isomer. These artifacts were not present in unrefined oils or bleached oils but could be induced by deodorization in the laboratory. Proportions of the two major artifacts in total 18:3ω3 are given for some vegetable oils from the retail market.
Expansion of solidifying saturated fats
Authors: Hvolby A.
Published: October 2004

From literature it appears that simple saturated triglycerides and commercial fats contract to a considerable extent when they undergo transformation from liquid to solid state and from an instable to a more stable crystalline form. In spite of these facts, the simple saturated even triglycerides and some fully hydrogenated fats exhibit violent solidification expansion by voluntary cooling. Solidification experiments carried out with several saturated even triglycerides and fats under various solidification conditions have shown that the solidification expansion tendency depends upon the chemical composition of the fat, as well as on the solidification conditions. The solidification expansion tendency is increased by various more or less independent factors, namely decreasing iodine value, increasing fatty acid and triglyceride uniformity, increasing triglyceride symmetry, increasing tendency to rapid formation of the stable β crystals, seeding with β crystals, voluntary cooling, moderate cooling velocity, and increasing bulk amount of fat. All the expanded solidified fats ended up being in the β crystalline form, whereas the nonexpanded fats ended up with the β’ form. The solidification expansion is avoidable by careful control of the cooling procedure.
Gas chromatographic analysis of nonionic surfactants by acid cleavage of ether linkages
Authors: Tsuji Kazuro , Konishi Kazuo
Published: October 2004

The gas chromatographic analysis of various kinds of nonionic surfactants has been carried out after chemical decomposition using the mixed anhydride of acetic and p‐toluene sulfonic acids which acts as a reagent for cleavage of ether linkages. The gas chromatographic peaks of the reaction products show the alkyl distributions of the hydrophobic groups of ethylene oxide adducts. The alkyl compositions closely agree with those of the starting materials. In this way, the hydrophobic groups of polyoxyethylene alkyl ether, polyoxyethylene alkyl phenol ether, polyoxyethylene alkyl amine, and polyoxyethylene alkyl thioether have been analyzed. At the same time, the hydrophilic group, namely polyoxyethylene group, can be identified in the form of ethylene glycol diacetate.
Production, chemistry, and commercial applications of various chemicals from castor oil
Authors: Naughton Frank C.
Published: October 2004

The presence of a hydroxyl group, in addition to an olefinic linkage, in the predominating fatty acid of castor oil gives this vegetable oil many unique and interesting properties. Castor oil consists largely of glycerides of ricinoleic acid or 12‐hydroxy octadecenoic acid. The chemical reactions of castor oil, undecylenic acid, 12‐hydroxylstearic acid, sebacic acid, and nylon 11, depict the uniqueness of this agricultural oil. By dehydration, castor oil is converted to a conjugated acid oil similar to tung or oiticica oil. The catalytic dehydration results in the formation of a new double bond in the fatty acid chain. The dehydrated castor oil imparts good flexibility, rapid dry, excellent color retention, and water resistance to protective coatings. The pyrolysis of castor oil cleaves the molecule to produce undecylenic acid and heptaldehyde. The pyrolysis of the methyl ester at 450–550 C results in the formation of methyl 10‐undecylenate. Hydrolysis of the methyl ester gives 10‐undecylenic acid. Hydrogen bromide is added to form 11‐bromo undecanoic, which is ammoniated and condensed to form a nylon polymer. When castor oil is added slowly to an 80% caustic solution, the sodium ricinoleate formed splits to form sodium sebacate and capryl alcohol. Sebacic acid is condensed with hexamethylene diamine to form nylon 6,10. The commercial application of castor oil derivatives in urethanes, starch gel modifiers, medium chain triglycerides, and thixotropic additives is reviewed briefly.
Feeding encapsulated oils to increase the polyunsaturation in milk and meat fat
Authors: Edmondson L. F. , Yoncoskie R. A. , Rainey N. H. , Douglas F. W. , Bitman Joel
Published: October 2004

Methods of preparing encapsulated, or protected vegetable oil supplements for feeding ruminant animals to increase the polyunsaturation in milk and meat fat are outlined. The C 18:2 content of milk from cows fed increasing amounts of protected safflower oil during a 6 week dose‐response experiment increased from 3 to 30% of total fat. At high levels of C 18:2 in milk fat, whole milks tended to develop an oxidized flavor, which was slight in fresh raw milk but increased markedly after 24 hr. Addition of an antioxidant to fresh milk suppressed this off‐flavor. Creams containing high levels of C 18:2 required longer aging times than normal cream for satisfactory churning. Butter containing 16% or more of C 18:2 was soft and somewhat sticky but was much more readily spreadable at refrigerator temperatures than normal butter. Veal fat from supplement fed calves had four times as much C 18:2 as fat from controls.
Use of oleic acid derivatives to accelerate drying of thompson seedless grapes
Authors: Petrucci Vincent , Canata Nick , Bolin H. R. , Fuller G. , Stafford A. E.
Published: October 2004

Pilot scale procedures were developed for the use of fatty acid ester emulsions to decrease the time to dry the Thompson seedless grapes to raisins. Both sun and mechanical drying were used in these experiments. Mechanically harvested grapes were dipped in a 1% or 2% fatty acid ester emulsion and dehydrated at drying times less than those required for the soda‐dipped raisins. Spraying grapes on the vine with a commercial ethyl ester mixture, which contained an emulsifier and added potassium carbonate, allowed the grapes to dry faster than the conventional sun drying procedures. These procedures produced light colored raisins of acceptable quality. In addition, these methods show savings by decreasing labor costs.
Fatty acid derivatives and glycolipids in high‐protein bakery products
Authors: Tsen Cho C.
Published: October 2004

High‐protein bakery foods, particularly breads, are ideal for alleviating protein malnutrition in poverty areas of the world. Fortifying wheat flour with a high level of protein‐rich additives like soy flour can, however, induce adverse effects upon dough properties and bread quality. Several fatty acid derivatives, including sucroesters, fatty esters of polyalkoxylated polyoglycosides, sodium or calcium stearoyl‐2 lactylate, and ethoxylated monoglycerides and glycolipids, recently have been shown to improve effectively the baking performance of wheat flour fortified with soy flour. The nutritional benefits of high‐protein breads are reported with results from feeding studies using the breads in diets of experimental rats. The possible mechanisms concerning the improving action of fatty acid derivatives are proposed and discussed.
Industrial applications for animal fatty oils
Authors: Hermann Christopher L. , McGlade Joseph J.
Published: October 2004

Some of the animal fats that are by‐products of the meat packing industry can become a valuable commodity for certain other portions of our nation's economy. This paper reviews the types of raw materials used, as well as the manufacturing techniques employed to manufacture these by‐products into useful animal oils. The industrial uses for these oils include, not only petroleum and metal processing, but also the chemical and pharmaceutical industries. These oils also can be reacted chemically to produce various extreme pressure additives for the petroleum industry. In some areas it is even replacing the oil from the sperm whale whose use has been banned within the U.S.
Pain in pediatric oncology — children's and parents' perspectives
Authors: Zernikow Boris , Meyerhoff Ulrike , Michel Erik , Wiesel Thomas , Hasan Carola , Janssen Gisela , Kuhn Nana , Kontny Udo , Fengler Rüdiger , Görtitz Irene , Andler Werner
Published: October 2004

There is a lack of valid epidemiological data on malignancy‐associated pain in modern pediatric oncology. Pediatric oncology patients (self‐assessment) and their parents from 28 hospitals were questioned using age‐adapted, structured interviews and validated pain assessment tools. Pain intensity was measured by the NRS and Bieri faces scale. We conducted 363 interviews with patients and their parents, and 46 with the parents alone (if patients <2.5 years). Pain was reported at the time of the interview or within the last 24 h, 7 d, or 4 weeks in 15%, 28%, 50% and 58% of cases, respectively. The proportion of patients suffering severe to maximal pain (NRS > 3; Bieri > 2) increased significantly (p = 0.001, χ2 test). The median pain intensity for the most severe pain episode within the last 4 weeks was 6.7 (NRS 0–10). Adverse effects of anti‐tumor therapy were the most frequent cause of pain. Multivariate analyses depicted general physical condition either “severely reduced” (ASA status 3) (OR 4.0, 95% CI 1.1‐14.7, p = 0.037) or “moderately reduced” (ASA status 2) (OR 1.8, 95% CI 1.1‐2.9, p = 0.018), “in‐patient status” (OR 1.8, 95% CI 1.2‐2.9, p = 0.010), and “co‐morbidity present” (OR 3.5, 95% CI 1.1‐10.7, p = 0.030) as risk factors for severe to maximal pain. General anesthesia was the only factor significantly (OR 0.14, 95% CI 0.05‐0.39, p < 0.01) associated with a reduction in the proportion of patients suffering severe to maximal pain during bone marrow aspiration. Our data emphasize both the importance of in‐house acute pain control and the need for general anesthesia during painful procedures in pediatric oncology.
Congenital cardiomyopathy and pulmonary hypertension: Another fatal variant of cytochrome‐c oxidase deficiency
Authors: Venditti C. P. , Harris M. C. , Huff D. , Peterside I. , Munson D. , Weber H. S. , Rome J. , Kaye E. M. , Shanske S. , Sacconi S. , Tay S. , DiMauro S. , Berry G. T.
Published: October 2004

Summary: Biventricular hypertrophy was noted at 24 weeks' gestation in a fetus with isolated cytochrome‐c oxidase (COX) deficiency. Shock, caused by hypertrophic cardiomyopathy and severe pulmonary hypertension, led to the patient's death on day 6. His phenotype defines a new lethal variant of COX deficiency characterized by prenatal‐onset cardiopulmonary pathophysiology.
NPT4, a new microsomal phosphate transporter: Mutation analysis in glycogen storage disease type Ic
Authors: Melis D. , Havelaar A. C. , Verbeek E. , Smit G. P. A. , Benedetti A. , Mancini G. M. S. , Verheijen F.
Published: October 2004

Summary: Deficiency of a microsomal phosphate transporter in the liver has been suggested in some patients affected by glycogen storage disease type Ic (GSD Ic). Several Na+/phosphate co‐transporters have been characterized as members of the anion‐cation symporter family. Recently, the cDNA sequence of two phosphate transporters, NPT3 and NPT4, expressed in liver, kidney and intestine, has been determined. We studied expression of human NPT4 in COS cells and observed an ER localization of the transporter by immunofluorescence microscopy. We speculated that this transporter could play a role in the regulation of the glucose‐6‐phosphatase (G6‐Pase) complex. We revealed the genomic structure of NPT4 and analysed the gene as a candidate for GSD Ic. DNA was collected from five patients without mutations in G6‐Pase or the G6‐P transporter gene. DNA analysis of NPT4 revealed that one patient was heterozygous for a G>A transition at nucleotide 601 which would result in a G201R substitution. Our results do not confirm the hypothesis that this gene is mutated in GSD Ic patients. However, we cannot exclude that the mutation found reduces the phosphate transport efficiency, possibly modulating the G6‐Pase complex.
Assessing the severity of the small inframe deletion mutation in the α‐subunit of β‐hexosaminidase A found in the Turkish population by reproducing it in the more stable β‐subunit
Authors: Sinici İ. , Tropak M. B. , Mahuran D. J. , Özkara H. A.
Published: October 2004

Summary: GM2 gangliosidoses are a group of panethnic lysosomal storage diseases in which GM2 ganglioside accumulates in the lysosome due to a defect in one of three genes, two of which encode the α‐ or β‐subunits of β‐N‐acetylhexosaminidase (Hex) A. A small inframe deletion mutation in the catalytic domain of the α‐subunit of Hex has been found in five Turkish patients with infantile Tay‐Sachs disease. To date it has not been detected in other populations and is the only mutation to be found in exon 10. It results in detectable levels of inactive α‐protein in its precursor form. Because the α‐ and β‐subunits share 60% sequence identity, the Hex A and Hex B genes are believed to have arisen from a common ancestral gene. Thus the subunits must share very similar three‐dimensional structures with conserved functional domains. Hex B, the β‐subunit homodimer is more stable than the heterodimeric Hex A, and much more stable than Hex S, the α homodimer. Thus, mutations that completely destabilize the α‐subunit can often be partially rescued if expressed in the aligned positions in the β‐subunit. To better understand the severity of the Turkish HEXA mutation, we reproduced the 12 bp deletion mutation (1267‐1278) in the β‐subunit cDNA. Western blot analysis of permanently transfected CHO cells expressing the mutant detected only the pro‐form of the β‐subunit coupled with a total lack of detectable Hex B activity. These data indicate that the deletion of the four amino acids severely affects the folding of even the more stable β‐subunit, causing its retention in the endoplasmic reticulum and ultimate degradation.
Animal models for glutaryl‐CoA dehydrogenase deficiency
Authors: Koeller D. M. , Sauer S. , Wajner M. , de Mello C. F. , Goodman S. I. , Woontner M. , Mühlhausen C. , Okun J. G. , KÖlker S.
Published: October 2004

Summary:In vitro studies suggest that excitotoxic cell damage is an underlying mechanism for the acute striatal damage in glutaryl‐CoA dehydrogenase (GCDH) deficiency. It is believed to result from an imbalance of glutamatergic and GABAergic neurotransmission induced by the accumulating organic acids 3‐hydroxyglutaric acid (3‐OH‐GA) and to a lesser extent glutaric acid (GA). Stereotaxic administration of 3‐OH‐GA and GA into the rat striatum have confirmed these results, but may not truly represent the effect of chronic exposure to these compounds. In an attempt to better understand the pathophysiology of GCDH deficiency in vivo, two animal models have been utilized. A mouse that lacks GCDH activity in all tissues was generated by gene targeting in embryonic stem cells. These animals develop the characteristic biochemical phenotype of the human disease. Pathologically, these mice have a diffuse spongiform myelinopathy similar to that in human patients; however, there is no evidence for acute striatal damage or sensitivity to acute encephalopathy induced by catabolism or inflammatory cytokines. A naturally occurring animal model, the fruit‐eating bat Rousettus aegypticus, lacks hepatic and renal GCDH activity, but retains cerebral enzyme activity. Like the mouse, these bats develop the characteristic biochemical phenotype of glutaryl‐CoA dehydrogenase deficiency, but lack overt neurological symptoms such as dystonia. It is not known whether they also develop the spongiform myelinopathy seen in the Gcdh‐deficient mice. Otherwise, these constellations would suggest that cerebral GCDH deficiency is responsible for the development of neuronal damage. The lack of striatal damage in these two rodent models may also be related to species differences. However, they also highlight our lack of a comprehensive understanding of additional factors that might modulate the susceptibiliy of neurons to accumulating 3‐OH‐GA and GA in GCDH deficiency. Unravelling these mechanisms may be the key to understanding the pathophysiology of this unique disease and to the development of neuroprotective strategies.
Glutaric aciduria type I and kynurenine pathway metabolites: A modified hypothesis
Authors: Varadkar S. , Surtees R.
Published: October 2004

Summary: Glutaric aciduria type I is an inborn error of organic acid metabolism that demonstrates a particular temporal vulnerability (acute encephalopathic episodes in infancy) and a spatial vulnerability (acute striatal necrosis, focused on the putamen). Excitotoxic mechanisms involving 3‐hydroxyglutaric acid as the major neurotoxin have been suggested. This paper proposes a role for metabolites of the kynurenine pathway in the pathogenic process and modifies the hypothesis of Heyes. Deficiency of glutaryl‐CoA dehydrogenase blocking the glutarate pathway and activation of indoleamine 2,3‐dioxygenase in macrophages/monocytes by intercurrent inflammation may increase flux down the kynurenine pathway towards the production of quinolinic acid. Quinolinic acid is neurotoxic and is an endogenous agonist at N‐methyl‐D‐aspartate receptors. Synergistic excitation of these receptors by quinolinic acid and 3‐hydroxyglutaric acid, which alone does not have sufficient potency, may be involved in the pathogenesis of striatal necrosis.
Neonatal screening for glutaryl‐CoA dehydrogenase deficiency
Authors: Lindner M. , KÖlker S. , Schulze A. , Christensen E. , Greenberg C. R. , Hoffmann G. F.
Published: October 2004

Summary: Acute encephalopathic crisis in glutaryl‐CoA dehydrogenase deficiency results in an unfavourable disease course and poor outcome, dominated by dystonia, feeding problems, seizures and secondary complications, and quite often leading to early death. The prerequisite for the prevention of irreversible brain damage in this disease is the detection of affected patients and initiation of treatment before the manifestation of such crisis. Apart from macrocephaly there are no signs or symptoms characteristic for this disease in presymptomatic children and, thus, they are usually missed. In some countries, implementation of extended neonatal screening programmes using electrospray ionization tandem mass spectrometry (ESI‐MS/MS) allows detection of affected newborns and start of therapy before onset of neurological complications. This article summarizes recent strategies, pitfalls and shortcomings of a mass screening for glutaryl‐CoA dehydrogenase deficiency using ESI‐MS/MS. Furthermore, an alternative strategy, namely DNA‐based neonatal screening for the Oji‐Cree variant of this disease, is demonstrated. An optimization of diagnostic as well as therapeutic procedures must be achieved before GCDH deficiency unequivocally fullfils the criteria of a reliable and successful newborn screening programme.
Neuroradiological findings in glutaric aciduria type I (glutaryl‐CoA dehydrogenase deficiency)
Authors: Neumaier‐Probst E. , Harting I. , Seitz A. , Ding C. , Kolker S.
Published: October 2004

Summary: This article summarizes the magnetic resonance imaging features of glutaric aciduria type I (GA I) based on the cases presented at the 3rd International Workshop on Glutaryl‐CoA Dehydrogenase Deficiency together with a review of previously reported neuroimaging characteristics of GA I. Previous reports have focused on characteristic findings, such as basal ganglia injury and frontotemporal atrophy or hypoplasia, subdural effusions and white‐matter disease. Most of these findings have been demonstrated in symptomatic children, i.e. after manifestation of acute encephalopathic crises. In contrast, prospective investigations in presymptomatically diagnosed children are rare. Since more recent investigations have highlighted CNS changes in patients without encephalopathic crises, systematic prospective investigations of neuroradiological findings in this disease are indispensable for a better understanding of this disease. Based on these findings a suggestion for a MRI protocol is presented, supporting a standardized evaluation of patients with GA I.
Nuclear magnetic resonance spectroscopy in glutaryl‐CoA dehydrogenase deficiency
Authors: Bodamer O. A. , Gruber S. , StÖckler‐Ipsiroglu S.
Published: October 2004

Summary: Nuclear magnetic resonance (NMR) spectroscopy is a safe, noninvasive method that is the preferred technique for in vivo analysis of specific chemical compounds in localized brain regions. Besides quantification of compounds, NMR spectroscopy allows the detailed analysis of neurotransmitter, glucose and lactate metabolism following peripheral infusions of stable isotopically labelled precursors. The latter has been successfully applied to patients with different neurological disease states not including glutaryl‐CoA dehydrogenase (GCDH) deficiency. In contrast, single patients with GCDH deficiency who were neurologically unremarkable have been studied with conflicting results. One patient was shown to have an increase in intracerebral creatine and phosphocreatine concentrations, while the second studied had unremarkable levels. In a 15‐year‐old patient, we were able to demonstrate elevated levels of intracerebral lactate and elevated choline/N‐acetylaspartate ratios, indicating potentially increased myelin turnover and reduced neuronal integrity in periventricular white matter. Interestingly, spectra in basal ganglia were within normal limits. Systematic studies to address well‐defined questions in GCDH deficiency are urgently needed. In particular, analysis of in vivo neurotransmitter metabolism following administration of isotopically labelled precursors in patients with GCDH deficiency, both when metabolically stable and when unstable, may help to advance our understanding of the pathophysiology of GCDH deficiency.
Emergency treatment in glutaryl‐CoA dehydrogenase deficiency
Authors: KÖlker S. , Greenberg C. R. , Lindner M. , Müller E. , Naughten E. R. , Hoffmann G. F.
Published: October 2004

Summary: The history of glutaryl‐CoA dehydrogenase deficiency is determined by acute encephalopathic crises that are precipitated by common febrile diseases, vaccinations or surgical interventions during infancy and early childhood. Such crises result in an irreversible destruction of the basal ganglia (in particular of the putamina), and consequently dystonia, dyskinesia and choreoathetosis. Secondary complications include feeding and speech problems, failure to thrive, recurrent aspiration, immobilization, severe motor deficits and early death. It is generally accepted that maintenance treatment based on dietary lysine or protein restriction and supplementation with carnitine (and riboflavin) is insufficient to prevent acute crises during intercurrent illnesses or conditions that enhance catabolic state. Consequently, outpatient and inpatient emergency therapies have been implemented. The present review describes a recommended approach to emergency therapy for this disease.
Stability of malonylcarnitine and glutarylcarnitine in stored blood spots
Authors: Johnson D. W. , Trinh> M.‐U.
Published: October 2004

Summary: Malonylcarnitine and glutarylcarnitine are important diagnostic metabolites in the screening of dried blood spots by tandem mass spectrometry. The stability of these compounds in spiked blood spots stored at room temperature was studied. Both showed biphasic curves. The malonylcarnitine concentration dropped to 61% in 38 days and averaged 51%±5% for the next 81 days. Glutarylcarnitine dropped to 60% in 42 days and averaged 56%±5% for the next 124 days.
S‐Acetylglutathione normalizes intracellular glutathione content in cultured fibroblasts from patients with glutathione synthetase deficiency
Authors: Okun J. G. , Sauer S. , Bähr S. , Lenhartz H. , Mayatepek E.
Published: October 2004

Summary: Glutathione synthetase deficiency is an autosomal recessive inherited metabolic defect in the γ‐glutamyl cycle. Decreased intracellular glutathione levels are one of the characteristic biochemical features. In this study we show that addition of S‐acetylglutathione to the medium raised intracellular glutathione content in cultured fibroblasts from patients with glutathione synthetase deficiency. This has implications for the treatment of patients with this inborn error of metabolism.
Hyperhydroxyprolinaemia detected in newborn screening with tandem mass spectrometry
Authors: Baykal T. , Karaaslan I. , Gokcay G. , Demir F. , Laleli Y. , Demirkol M.
Published: October 2004

Summary: Hydroxyproline has the same integer molecular weight as leucine and isoleucine and is quantified with these by tandem mass spectrometry. An infant was diagnosed with hyperhydroxyprolinaemia following further evaluation of an elevated “leucine” level in newborn screening by tandem mass spectrometry.
Two successful pregnancies in pyridoxine‐nonresponsive homocystinuria
Authors: Vilaseca M. A. , Cuartero M. L. , Martinez de Salinas M. , Lambruschini N. , Pintó X. , Urreizti R. , Balcells S. , Grinberg D.
Published: October 2004

Summary: Two successful pregnancies are reported in a pyridoxine‐nonresponsive woman who was also homozygous for the MTHFR 677C>T polymorphism. Two healthy children were delivered, although there had also been an early miscarriage of an apparently normal fetus in another pregnancy. Management of the patient's homocystine and methionine levels was maintained throughout pregnancy and, in view of the increased thromoboembolic risk, anticoagulation therapy was also included in the management.
Mutational analysis of carbamoylphosphate synthetase I deficiency in three Japanese patients
Authors: Wakutani Y. , Nakayasu H. , Takeshima T. , Adachi M. , Kawataki M. , Kihira K. , Sawada H. , Bonno M. , Yamamoto H. , Nakashima K.
Published: October 2004

Summary: We describe the results of mutational analysis of the carbamoylphosphate synthetase I (CPSI) gene in three nonconsanguineous patients with CPSI deficiency. Compound heterozygotes of 3422T/G (V1141G) plus 3784C/T (R1262X), 1528delG (510‐514 ARQLX) plus 2752T/C (S918P), and 2549G/A (R850H) plus 2797delT (L933X) were identified through genomic analysis; however, the 2797delT (L933X) mutation was not detected in cDNA analysis using biopsied liver, suggesting that mRNA expression from this mutant allele is absent or markedly low.
A Poisson regression model approach to predicting tropical cyclogenesis in the Australian/southwest Pacific Ocean region using the SOI and saturated equivalent potential temperature gradient as predictors
Authors: McDonnell Katrina A. , Holbrook Neil J.
Published: October 2004

This paper explores the potential of the Southern Oscillation index (SOI) in combination with the saturated equivalent potential temperature gradient (EPT) as predictors of tropical cyclogenesis in the Australian/southwest Pacific Ocean. This is undertaken using a series of Poisson regression models of tropical cyclogenesis developed on a 2° latitude × 5° longitude and monthly grid. Links between tropical cyclogenesis and the predictors are investigated, with the most significant models cross‐validated, and the skill of their hindcasts evaluated. The September lead SOI‐only Poisson regression model provided skillful predictions of the temporal variability of tropical cyclogenesis across the entire region, with a root‐mean‐square error 22% better than climatology. The combination SOI and EPT model adds spatial skill and further improves temporal skill. Temporal skill is best in the Eastern subregion (western tropical Pacific) (significant correlations with observations at ∼99% level), while spatial skill is best elsewhere.
A general power equation for predicting bed load transport rates in gravel bed rivers
Authors: Barry Jeffrey J. , Buffington John M. , King John G.
Published: October 2004

A variety of formulae has been developed to predict bed load transport in gravel bed rivers, ranging from simple regressions to complex multiparameter formulations. The ability to test these formulae across numerous field sites has, until recently, been hampered by a paucity of bed load transport data for gravel bed rivers. We use 2104 bed load transport observations in 24 gravel bed rivers in Idaho to assess the performance of eight different formulations of four bed load transport equations. Results show substantial differences in performance but no consistent relationship between formula performance and degree of calibration or complexity. However, formulae containing a transport threshold typically exhibit poor performance. Furthermore, we find that the transport data are best described by a simple power function of discharge. From this we propose a new bed load transport equation and identify channel and watershed characteristics that control the exponent and coefficient of the proposed power function. We find that the exponent is principally a factor of supply‐related channel armoring (transport capacity in excess of sediment supply), whereas the coefficient is related to drainage area (a surrogate for absolute sediment supply). We evaluate the accuracy of the proposed power function at 17 independent test sites.
Purified recombinant human prosaposin forms oligomers that bind procathepsin D and affect its autoactivation
Authors: GOPALAKRISHNAN Madanan Madathiparambil , GROSCH Hans-Wilhelm , LOCATELLI-HOOPS Silvia , WERTH Norbert , SMOLENOVÁ Eva , NETTERSHEIM Michael , SANDHOFF Konrad , HASILIK Andrej
Published: October 2004

Before delivery to endosomes, portions of proCD (procathepsin D) and proSAP (prosaposin) are assembled into complexes. We demonstrate that such complexes are also present in secretions of cultured cells. To study the formation and properties of the complexes, we purified proCD and proSAP from culture media of Spodoptera frugiperda cells that were infected with baculoviruses bearing the respective cDNAs. The biological activity of proCD was demonstrated by its pH-dependent autoactivation to pseudocathepsin D and that of proSAP was demonstrated by feeding to saposin-deficient cultured cells that corrected the storage of radioactive glycolipids. In gel filtration, proSAP behaved as an oligomer and proCD as a monomer. ProSAP altered the elution of proCD such that the latter was shifted into proSAP-containing fractions. ProSAP did not change the elution of mature cathepsin D. Using surface plasmon resonance and an immobilized biotinylated proCD, binding of proSAP was demonstrated under neutral and weakly acidic conditions. At pH 6.8, specific binding appeared to involve more than one binding site on a proSAP oligomer. The dissociation of the first site was characterized by a KD1 of 5.8±2.9×10−8 M−1 (calculated for the monomer). ProSAP stimulated the autoactivation of proCD and also the activity of pseudocathepsin D. Concomitant with the activation, proSAP behaved as a substrate yielding tri- and disaposins and smaller fragments. Our results demonstrate that proSAP forms oligomers that are capable of binding proCD spontaneously and independent of the mammalian type N-glycosylation but not capable of binding mature cathepsin D. In addition to binding proSAP, proCD behaves as an autoactivable and processing enzyme and its binding partner as an activator and substrate.
Structural organization of mitochondrial human complex I: role of the ND4 and ND5 mitochondria-encoded subunits and interaction with prohibitin
Authors: BOURGES Ingrid , RAMUS Claire , MOUSSON de CAMARET Bénédicte , BEUGNOT Réjane , REMACLE Claire , CARDOL Pierre , HOFHAUS Götz , ISSARTEL Jean-Paul
Published: October 2004

Mitochondria-encoded ND (NADH dehydrogenase) subunits, as components of the hydrophobic part of complex I, are essential for NADH:ubiquinone oxidoreductase activity. Mutations or lack of expression of these subunits have significant pathogenic consequences in humans. However, the way these events affect complex I assembly is poorly documented. To understand the effects of particular mutations in ND subunits on complex I assembly, we studied four human cell lines: ND4 non-expressing cells, ND5 non-expressing cells, and rho° cells that do not express any ND subunits, in comparison with normal complex I control cells. In control cells, all the seven analysed nuclear-encoded complex I subunits were found to be attached to the mitochondrial inner membrane, except for the 24 kDa subunit, which was nearly equally partitioned between the membranes and the matrix. Absence of a single ND subunit, or even all the seven ND subunits, caused no major changes in the nuclear-encoded complex I subunit content of mitochondria. However, in cells lacking ND4 or ND5, very low amounts of 24 kDa subunit were found associated with the membranes, whereas most of the other nuclear-encoded subunits remained attached. In contrast, membrane association of most of the nuclear subunits was significantly reduced in the absence of all seven ND proteins. Immunopurification detected several subcomplexes. One of these, containing the 23, 30 and 49 kDa subunits, also contained prohibitin. This is the first description of prohibitin interaction with complex I subunits and suggests that this protein might play a role in the assembly or degradation of mitochondrial complex I.
The G115S mutation associated with maturity-onset diabetes of the young impairs hepatocyte nuclear factor 4α activities and introduces a PKA phosphorylation site in its DNA-binding domain
Authors: OXOMBRE Bénédicte , KOUACH Mostafa , MOERMAN Ericka , FORMSTECHER Pierre , LAINE Bernard
Published: October 2004

HNF4α (hepatocyte nuclear factor 4α) belongs to a complex transcription factor network that is crucial for the function of hepatocytes and pancreatic β-cells. In these cells, it activates the expression of a very large number of genes, including genes involved in the transport and metabolism of glucose and lipids. Mutations in the HNF4α gene correlate with MODY1 (maturity-onset diabetes of the young 1), a form of type II diabetes characterized by an impaired glucose-induced insulin secretion. The MODY1 G115S (Gly115→Ser) HNF4α mutation is located in the DNA-binding domain of this nuclear receptor. We show here that the G115S mutation failed to affect HNF4α-mediated transcription on apolipoprotein promoters in HepG2 cells. Conversely, in pancreatic β-cell lines, this mutation resulted in strong impairments of HNF4α transcriptional activity on the promoters of LPK (liver pyruvate kinase) and HNF1α, with this transcription factor playing a key role in endocrine pancreas. We show as well that the G115S mutation creates a PKA (protein kinase A) phosphorylation site, and that PKA-mediated phosphorylation results in a decreased transcriptional activity of the mutant. Moreover, the G115E (Gly115→Glu) mutation mimicking phosphorylation reduced HNF4α DNA-binding and transcriptional activities. Our results may account for the 100% penetrance of diabetes in human carriers of this mutation. In addition, they suggest that introduction of a phosphorylation site in the DNA-binding domain may represent a new mechanism by which a MODY1 mutation leads to loss of HNF4α function.
Characterization of a novel low-molecular-mass dual-specificity phosphatase-3 (LDP-3) that enhances activation of JNK and p38
Authors: TAKAGAKI Kentaro , SATOH Takeshi , TANUMA Nobuhiro , MASUDA Kouhei , TAKEKAWA Mutsuhiro , SHIMA Hiroshi , KIKUCHI Kunimi
Published: October 2004

We have isolated a mouse cDNA for a novel dual-specificity phosphatase designated LDP-3 (low-molecular-mass dual-specificity phosphatase 3). The 450 bp open reading frame encodes a protein of 150 amino acids with a predicted molecular mass of 16 kDa. Northern blot and reverse transcription–PCR analyses show that LDP-3 transcripts are expressed in almost all mouse tissues examined. In vitro analyses using several substrates and inhibitors indicate that LDP-3 possesses intrinsic dual-specificity phosphatase activity. When expressed in mammalian cells, LDP-3 protein is localized mainly to the apical submembrane area. Forced expression of LDP-3 does not alter activation of ERK (extracellular-signal-regulated kinase), but rather enhances activation of JNK (c-Jun N-terminal kinase) and p38 and their respective upstream kinases MKK4 (mitogen-activated protein kinase kinase 4) and MKK6 in cells treated with 0.4 M sorbitol. By screening with a variety of stimuli, we found that LDP-3 specifically enhances the osmotic stress-induced activation of JNK and p38.
Brassica juncea 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase 1: expression and characterization of recombinant wild-type and mutant enzymes
Authors: NAGEGOWDA Dinesh A. , BACH Thomas J. , CHYE Mee-Len
Published: October 2004

3-Hydroxy-3-methylglutaryl (HMG)-CoA synthase (HMGS; EC 2.3.3.10) is the second enzyme in the cytoplasmic mevalonate pathway of isoprenoid biosynthesis, and catalyses the condensation of acetyl-CoA with acetoacetyl-CoA (AcAc-CoA) to yield S-HMG-CoA. In this study, we have first characterized in detail a plant HMGS, Brassica juncea HMGS1 (BjHMGS1), as a His6-tagged protein from Escherichia coli. Native gel electrophoresis analysis showed that the enzyme behaves as a homodimer with a calculated mass of 105.8 kDa. It is activated by 5 mM dithioerythreitol and is inhibited by F-244 which is specific for HMGS enzymes. It has a pH optimum of 8.5 and a temperature optimum of 35 °C, with an energy of activation of 62.5 J·mol−1. Unlike cytosolic HMGS from chicken and cockroach, cations like Mg2+, Mn2+, Zn2+ and Co2+ did not stimulate His6–BjHMGS1 activity in vitro; instead all except Mg2+ were inhibitory. His6–BjHMGS1 has an apparent Km-acetyl-CoA of 43 μM and a Vmax of 0.47 μmol·mg−1·min−1, and was inhibited by one of the substrates (AcAc-CoA) and by both products (HMG-CoA and HS-CoA). Site-directed mutagenesis of conserved amino acid residues in BjHMGS1 revealed that substitutions R157A, H188N and C212S resulted in a decreased Vmax, indicating some involvement of these residues in catalytic capacity. Unlike His6–BjHMGS1 and its soluble purified mutant derivatives, the H188N mutant did not display substrate inhibition by AcAc-CoA. Substitution S359A resulted in a 10-fold increased specific activity. Based on these kinetic analyses, we generated a novel double mutation H188N/S359A, which resulted in a 10-fold increased specific activity, but still lacking inhibition by AcAc-CoA, strongly suggesting that His-188 is involved in conferring substrate inhibition on His6–BjHMGS1. Substitution of an aminoacyl residue resulting in loss of substrate inhibition has never been previously reported for any HMGS.
Two new FUT2 (fucosyltransferase 2 gene) missense polymorphisms, 739G→A and 839T→C, are partly responsible for non-secretor status in a Caucasian population from Northern Portugal
Authors: SERPA Jacinta , MENDES Nuno , REIS Celso A. , SANTOS SILVA Luis F. , ALMEIDA Raquel , LE PENDU Jacques , DAVID Leonor
Published: October 2004

Secretor status is defined by the expression of H type 1 antigen on gastric surface epithelium and external secretions. The H type 1 structure, and other fucosylated carbohydrates (Lea, sialyl-Lea, Leb, Lex, sialyl-Lex and Ley), can serve as ligands for several pathogens, including Helicobacter pylori, and are cancer-associated antigens. Secretor individuals are more susceptible to some bacterial and viral infections of the genito-urinary and digestive tracts. The aim of the present study was to examine FUT2 (fucosyltransferase 2 gene) polymorphisms in a Caucasian population of non-secretor individuals (n=36) from northern Portugal and to evaluate the activity of the mutant FUT2 enzymes. The secretor status was determined by UEAI [Ulex europaeus (gorse) lectin] histochemistry in gastric mucosa, and FUT2 polymorphisms were studied by restriction-fragment-length polymorphism and direct sequencing. The majority of non-secretors (88.9%) were homozygous for 428G→A polymorphism; 5.6% were homozygous for 571C→T and 5.6% were homozygous for two new missense polymorphisms, 739G→A (2.8%) and 839T→C (2.8%). By kinetic studies it was demonstrated that the two new FUT2 mutants (739G→A and 839T→C) are almost inactive and are responsible for some non-secretor cases.
Matrix metalloproteinase-2 cleavage of adrenomedullin produces a vasoconstrictor out of a vasodilator
Authors: MARTÍNEZ Alfredo , OH Hae-Ryong , UNSWORTH Edward J. , BREGONZIO Claudia , SAAVEDRA Juan M. , STETLER-STEVENSON William G. , CUTTITTA Frank
Published: October 2004

MMPs (matrix metalloproteinases) play a major role in the pathogenesis of hypertension by altering the extracellular matrix during cardiovascular remodelling. In the present study we show that MMP-2, but not MMP-9, cleaves the vasodilator peptide AM (adrenomedullin). Addition of the AM-binding protein, complement factor H, prevents this cleavage, providing a hitherto unknown mechanism of action for this binding protein. We identified the signature cleavage fragments and found some of them in human urine, suggesting that MMP-2 processing of AM may occur in vivo. Synthetic AM fragments regulated blood pressure in rats. The larger peptides are vasodilators, as is intact AM, whereas intermediate fragments did not affect blood pressure. In contrast, AM(11–22) elicited vasoconstriction. Studies of AM receptor activation in Rat2 cells confirm that the larger AM cleavage peptides activated this receptor, whereas AM(11–22) did not. The present study defines a new mechanism through which MMP-2 may regulate blood pressure by simultaneously eliminating a vasodilator and generating a vasoconstrictor.