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G Fuchs

Publications and source records attributed to G Fuchs.

At least 19 recordsLinked to original sources
PubMed2006

[Total hip arthroplasty in cerebral palsy].

BACKGROUND: The treatment of painful osteoarthritis of the hip in cerebral palsy requires a therapy concept that considers the pathoanatomical features and adapts the treatment to the individual physical and mental abilities. Femoral head resection has been proven be effective in severely dislocated hip joints in completely immobilized patients, whereas no satisfactory outcome is achieved in those patients with sufficient walking ability and moderate expression of spasticity. RESULTS: The following study investigates the results of total hip replacement (THR) in patients with tetraspastic cerebral palsy. Between 1992 and 2004, 19 total hip arthroplasties were performed in 175 patients with an average follow-up of 4,6 years. In all patients the walking ability improved significantly; 84% of the patients were pain free. Aseptic loosening of the femoral component was registered in one patient. A periprosthetic fracture in another patient required the implantation of a modular non-cemented femoral component. CONCLUSION: In this study total hip arthroplasty represents an important expansion of operative treatment options in secondary osteoarthritis of cerebral palsy in selected and cooperative patients. Taking the contradictions into consideration (severe athetosis, absence of adequate weight bearing, severe pelvic obliquity), THR promises to be an effective alternative to femoral head resection with significant pain reduction and improvement of walking abilities.

Adult↗
PubMed2003

The Cologne Carbon Cluster experiment: ro-vibrational spectroscopy on C8 and other small carbon clusters.

We report on our ongoing efforts in obtaining the IR-spectra of the linear carbon cluster molecules Cn with n=8-13. So far C8, C9, C10, and C13 have been recorded at Cologne. With the exception of C8 all assignments have been secured. For C8 a tentative assignment could be derived with the bandcenter of the sigmau antisymmetric stretching mode located at nu0=2067.9779 cm(-1) and a preliminary rotational constant in the vibrational ground state of B"=0.02068 cm(-1). The measured signal to noise ratio of the ro-vibrational band is fairly weak and thus the lower J ro-vibrational transitions can not be assigned with certainty. As a consequence the band center remains uncertain by 4 J or 0.17 cm(-1). For a more reliable assignment the sensitivity of the system has to be increased by at least one order of magnitude. The envisaged sensitivity increase of our experiment will be discussed along with the intention to perform terahertz observations of the low energetic bending ro-vibrational spectra. These sub-mm wave measurements will be carried out simultaneously with the IR measurements.

Carbon↗
PubMed2002

Which factors influence therapeutic decisions in Parkinson's disease?

Development of dyskinesia is a common phenomenon during the long-term course of Parkinson's disease. During the last few years, some but not all pathogenetic mechanisms causing dyskinesias in PD have become better understood. Severity of Parkinson's disease and levodopa dosing are the main clinical risk factors. Most concepts underline the significance of pulsatile D1-receptor stimulation for the development of dyskinesias. The interactions between D1- and D2-mediated STR-Gpi pathways and colocalized neuropeptides are important but not fully understood. Glutamatergic overactivity might also be a significant pathogenetic factor. According to these pathophysiological concepts, therapeutic strategies focus mainly on continuous postsynaptic DA-receptor stimulation by long-acting DA-agonists or highly selective D2-agonists. Another strategy is the use of NMDA antagonists.

Age Factors↗
PubMed2001

Redox centers of 4-hydroxybenzoyl-CoA reductase, a member of the xanthine oxidase family of molybdenum-containing enzymes.

4-Hydroxybenzoyl-CoA reductase (4-HBCR) is a key enzyme in the anaerobic metabolism of phenolic compounds. It catalyzes the reductive removal of the hydroxyl group from the aromatic ring yielding benzoyl-CoA and water. The subunit architecture, amino acid sequence, and the cofactor/metal content indicate that it belongs to the xanthine oxidase (XO) family of molybdenum cofactor-containing enzymes. 4-HBCR is an unusual XO family member as it catalyzes the irreversible reduction of a CoA-thioester substrate. A radical mechanism has been proposed for the enzymatic removal of phenolic hydroxyl groups. In this work we studied the spectroscopic and electrochemical properties of 4-HBCR by EPR and Mössbauer spectroscopy and identified the pterin cofactor as molybdopterin mononucleotide. In addition to two different [2Fe-2S] clusters, one FAD and one molybdenum species per monomer, we also identified a [4Fe-4S] cluster/monomer, which is unique among members of the XO family. The reduced [4Fe-4S] cluster interacted magnetically with the Mo(V) species, suggesting that the centers are in close proximity, (<15 A apart). Additionally, reduction of the [4Fe-4S] cluster resulted in a loss of the EPR signals of the [2Fe-2S] clusters probably because of magnetic interactions between the Fe-S clusters as evidenced in power saturation studies. The Mo(V) EPR signals of 4-HBCR were typical for XO family members. Under steady-state conditions of substrate reduction, in the presence of excess dithionite, the [4Fe-4S] clusters were in the fully oxidized state while the [2Fe-2S] clusters remained reduced. The redox potentials of the redox cofactors were determined to be: [2Fe-2S](+1/+2) I, -205 mV; [2Fe-2S] (+1/+2) II, -255 mV; FAD/FADH( small middle dot)/FADH, -250 mV/-470 mV; [4Fe-4S](+1/+2), -465 mV and Mo(VI)/(V)/(VI), -380 mV/-500 mV. A catalytic cycle is proposed that takes into account the common properties of molybdenum cofactor enzymes and the special one-electron chemistry of dehydroxylation of phenolic compounds.

Catalysis↗
PubMed2001

Single turnover EPR studies of benzoyl-CoA reductase.

Benzoyl-CoA reductase (BCR) catalyzes the ATP-driven transport of two electrons from a reduced 2[4Fe-4S] ferredoxin to the aromatic ring of benzoyl-CoA. A mechanism involving radical species and very low potential electrons similar to the Birch reduction of aromatics has been suggested for this reaction. The redox centers of BCR have previously been identified, by EPR- and Mössbauer spectroscopy, to be three cysteine-ligated [4Fe-4S] clusters [Boll et al. (2000) J. Biol. Chem. 275, 31857-31868] with redox potentials more negative than -500 mV. In this work, the catalytic cycle of BCR was studied by freeze-quench experiments; the dithionite reduced enzyme was rapidly mixed with equimolar amounts of benzoyl-CoA and excess MgATP plus dithionite, and subjected to EPR spectroscopic analysis. The turnover period of the enzyme under the conditions used was 3 s. The total S = (1)/(2) spin concentration increased 3-fold very rapidly (within approximately 25 ms). In the course of a single turnover the extent of enzyme reduction decreased again, finally reaching the starting value. An increased magnetic interaction of [4Fe-4S] clusters and the rise of an S = (7)/(2) high-spin EPR signal occurred as second simultaneous and transient events (at approximately 200 ms). Previous work showed that binding of the nucleotide affects the magnetic interaction of [4Fe-4S] clusters, whereas hydrolysis of MgATP is required for the switch to high-spin EPR signals. Finally, two novel transient EPR signals with an isotropic line-shape developed maximally in the late phase of the catalytic cycle ( approximately 1-2 s). These signals differed from those of typical free radicals by shifted g values at g = 2.015 and g = 2.033 and by an unusually fast relaxation rate, suggesting an interaction of these paramagnetic species with [4Fe-4S](+1) clusters. On the basis of these results, we present a proposal for a catalytic cycle involving radical species.

Acyl Coenzyme A↗
PubMed2001

Biosynthetic controls on the 13C contents of organic components in the photoautotrophic bacterium Chloroflexus aurantiacus.

To assess the effects related to known and proposed biosynthetic pathways on the (13)C content of lipids and storage products of the photoautotrophic bacterium Chloroflexus aurantiacus, the isotopic compositions of bulk cell material, alkyl and isoprenoid lipids, and storage products such as glycogen and polyhydroxyalkanoic acids have been investigated. The bulk cell material was 13 per thousand depleted in (13)C relative to the dissolved inorganic carbon. Evidently, inorganic carbon fixation by the main carboxylating enzymes used by C. aurantiacus, which are assumed to use bicarbonate rather than CO(2), results in a relatively small carbon isotopic fractionation compared with CO(2) fixation by the Calvin cycle. Even carbon numbered fatty acids, odd carbon numbered fatty acids, and isoprenoid lipids were 14, 15, and 17-18 per thousand depleted in (13)C relative to the carbon source, respectively. Based on the (13)C contents of alkyl and isoprenoid lipids, a 40 per thousand difference in (13)C content between the carboxyl and methyl carbon from acetyl-coenzyme A has been calculated. Both sugars and polyhydroxyalkanoic acid were enriched in (13)C relative to the alkyl and isoprenoid lipids. To the best of our knowledge this is the first report in which the stable carbon isotopic composition of a large range of biosynthetic products in a photoautotrophic organism has been investigated and interpreted based on previously proposed inorganic carbon fixation and biosynthetic pathways. Our results indicate that compound-specific stable carbon isotope analysis may provide a rapid screening tool for carbon fixation pathways.

Alkanes↗
PubMed2001

A novel pathway of aerobic benzoate catabolism in the bacteria Azoarcus evansii and Bacillus stearothermophilus.

The aerobic catabolism of benzoate was studied in the Gram-negative proteobacterium Azoarcus evansii and in the Gram-positive bacterium Bacillus stearothermophilus. In contrast to earlier proposals, benzoate was not converted into hydroxybenzoate or gentisate. Rather, benzoyl-CoA was a product of benzoate catabolism in both microbial species under aerobic conditions in vivo. Benzoyl-CoA was converted into various CoA thioesters by cell extracts of both species in oxygen- and NADPH-dependent reactions. Using [ring-(13)C(6)]benzoyl-CoA as substrate, cis-3,4-[2,3,4,5,6-(13)C(5)]dehydroadipyl-CoA, trans-2,3-[2,3,4,5,6-(13)C(5)]dehydroadipyl-CoA, the 3,6-lactone of 3-[2,3,4,5,6-(13)C(5)]hydroxyadipyl-CoA, and 3-[2,3,4,5,6-(13)C(5)]hydroxyadipyl-CoA were identified as products by NMR spectroscopy. A protein mixture of A. evansii transformed [ring-(13)C(6)]benzoyl-CoA in an NADPH- and oxygen-dependent reaction into 6-[2,3,4,5,6-(13)C(5)]hydroxy-3-hexenoyl-CoA. The data suggest a novel aerobic pathway of benzoate catabolism via CoA intermediates leading to beta-ketoadipyl-CoA, an intermediate of the known beta-ketoadipate pathway.

Acyl Coenzyme A↗
PubMed2001

Stable carbon isotope fractionations of the hyperthermophilic crenarchaeon Metallosphaera sedula.

The stable carbon isotopic compositions of the inorganic carbon source, bulk cell material, and isoprenoid lipids of the hyperthermophilic crenarchaeon Metallosphaera sedula, which uses a 3-hydroxypropionate-like pathway for autotrophic carbon fixation, have been measured. Bulk cell material was approximately 3 per thousand enriched in 13C relative to the dissolved inorganic carbon, and 2 per thousand depleted in 13C relative to isoprenoid membrane lipids. The isotope data suggested that M. sedula uses mainly bicarbonate rather than CO(2) as inorganic carbon source, which is in accordance with a 3-hydroxypropionate-like carbon fixation pathway. To the best of our knowledge this is the first report of 13C fractionation effects of such a hyperthermophilic crenarchaeon.

Bicarbonates↗
PubMed2001

Biosynthetic controls on the 13C contents of organic components in the photoautotrophic bacterium Chloroflexus aurantiacus.

To assess the effects related to known and proposed biosynthetic pathways on the (13)C content of lipids and storage products of the photoautotrophic bacterium Chloroflexus aurantiacus, the isotopic compositions of bulk cell material, alkyl and isoprenoid lipids, and storage products such as glycogen and polyhydroxyalkanoic acids have been investigated. The bulk cell material was 13 per thousand depleted in (13)C relative to the dissolved inorganic carbon. Evidently, inorganic carbon fixation by the main carboxylating enzymes used by C. aurantiacus, which are assumed to use bicarbonate rather than CO(2), results in a relatively small carbon isotopic fractionation compared with CO(2) fixation by the Calvin cycle. Even carbon numbered fatty acids, odd carbon numbered fatty acids, and isoprenoid lipids were 14, 15, and 17-18 per thousand depleted in (13)C relative to the carbon source, respectively. Based on the (13)C contents of alkyl and isoprenoid lipids, a 40 per thousand difference in (13)C content between the carboxyl and methyl carbon from acetyl-coenzyme A has been calculated. Both sugars and polyhydroxyalkanoic acid were enriched in (13)C relative to the alkyl and isoprenoid lipids. To the best of our knowledge this is the first report in which the stable carbon isotopic composition of a large range of biosynthetic products in a photoautotrophic organism has been investigated and interpreted based on previously proposed inorganic carbon fixation and biosynthetic pathways. Our results indicate that compound-specific stable carbon isotope analysis may provide a rapid screening tool for carbon fixation pathways.

Alkanes↗
PubMed2001

Management of severe malnutrition and diarrhea.

Children with severe malnutrition and diarrhea have high mortality rates that have been attributed to faulty case-management. Health workers are often unaware of the unique treatment requirements of severely malnourished children resulting in improper case-management. Moreover, the lack of prescriptive guidelines promotes the exercise of discretion in case-management that is often detrimental. Appropriate feeding from the start of treatment, routine micronutrient supplementation, broad-spectrum antibiotic therapy, less use of intravenous fluids for rehydration, and careful management of complications are factors that can reduce death, morbidity and cost of treating children with severe malnutrition and acute illnesses including diarrhea. In this paper is discussed a standardized protocol based upon the above mentioned factors for the management of severely malnourished children with acute illnesses including diarrhea. Implementation of the protocol resulted in a 47% reduction in mortality in these children.

Acute Disease↗
PubMed2001

Increased nitrite and nitrate concentrations in sera and urine of patients with cholera or shigellosis.

OBJECTIVES: Nitric oxide (NO) is an important regulator of cell function. In the intestine, NO regulates blood flow, peristalsis, secretion, and is associated with inflammation and tissue injury. The objectives of this study were to assess and compare the role of NO in cholera, a noninflammatory enteric infection, and in shigellosis, a bacterial inflammation of the colon. METHODS: We determined serum and urinary concentrations of nitrite and nitrate during acute illness and early convalescence in 45 hospitalized children: 24 with cholera and 21 with shigellosis; 18 healthy children served as controls. Nitrite and nitrate concentrations were determined spectrophotometrically using Greiss reaction-dependent enzyme assay. RESULTS: Serum nitrite and nitrate concentrations were significantly (p < 0.05) increased during acute illness compared to the early convalescence in both cholera and shigellosis. Urinary nitrite and nitrate excretions were significantly (p < 0.01) increased during acute disease in shigellosis, but not in cholera. Nitrite concentrations correlated with stool volume (r2 = 0.851) in cholera and with leukocytosis (r2 = 0.923) in shigellosis. CONCLUSIONS: Both cholera and shigellosis are associated with increased production of NO, suggesting its pathophysiologic roles in these diseases.

Acute Disease↗
PubMed2001

Autotrophic CO(2) fixation by Chloroflexus aurantiacus: study of glyoxylate formation and assimilation via the 3-hydroxypropionate cycle.

In the facultative autotrophic organism Chloroflexus aurantiacus, a phototrophic green nonsulfur bacterium, the Calvin cycle does not appear to be operative in autotrophic carbon assimilation. An alternative cyclic pathway, the 3-hydroxypropionate cycle, has been proposed. In this pathway, acetyl coenzyme A (acetyl-CoA) is assumed to be converted to malate, and two CO(2) molecules are thereby fixed. Malyl-CoA is supposed to be cleaved to acetyl-CoA, the starting molecule, and glyoxylate, the carbon fixation product. Malyl-CoA cleavage is shown here to be catalyzed by malyl-CoA lyase; this enzyme activity is induced severalfold in autotrophically grown cells. Malate is converted to malyl-CoA via an inducible CoA transferase with succinyl-CoA as a CoA donor. Some enzyme activities involved in the conversion of malonyl-CoA via 3-hydroxypropionate to propionyl-CoA are also induced under autotrophic growth conditions. So far, no clue as to the first step in glyoxylate assimilation has been obtained. One possibility for the assimilation of glyoxylate involves the conversion of glyoxylate to glycine and the subsequent assimilation of glycine. However, such a pathway does not occur, as shown by labeling of whole cells with [1,2-(13)C(2)]glycine. Glycine carbon was incorporated only into glycine, serine, and compounds that contained C(1) units derived therefrom and not into other cell compounds.

Acetyl Coenzyme A↗
PubMed2001

Two similar gene clusters coding for enzymes of a new type of aerobic 2-aminobenzoate (anthranilate) metabolism in the bacterium Azoarcus evansii.

In the beta-proteobacterium Azoarcus evansii, the aerobic metabolism of 2-aminobenzoate (anthranilate), phenylacetate, and benzoate proceeds via three unprecedented pathways. The pathways have in common that all three substrates are initially activated to coenzyme A (CoA) thioesters and further processed in this form. The two initial steps of 2-aminobenzoate metabolism are catalyzed by a 2-aminobenzoate-CoA ligase forming 2-aminobenzoyl-CoA and by a 2-aminobenzoyl-CoA monooxygenase/reductase (ACMR) forming 2-amino-5-oxo-cyclohex-1-ene-1-carbonyl-CoA. Eight genes possibly involved in this pathway, including the genes encoding 2-aminobenzoate-CoA ligase and ACMR, were detected, cloned, and sequenced. The sequence of the ACMR gene showed that this enzyme is an 87-kDa fusion protein of two flavoproteins, a monooxygenase (similar to salicylate monooxygenase) and a reductase (similar to old yellow enzyme). Besides the genes for the initial two enzymes, genes for three enzymes of a beta-oxidation pathway were found. A substrate binding protein of an ABC transport system, a MarR-like regulator, and a putative translation inhibitor protein were also encoded by the gene cluster. The data suggest that, after monooxygenation/reduction of 2-aminobenzoyl-CoA, the nonaromatic CoA thioester intermediate is metabolized further by beta-oxidation. This implies that all subsequent intermediates are CoA thioesters and that the alicyclic carbon ring is not cleaved oxygenolytically. Surprisingly, the cluster of eight genes, which form an operon, is duplicated. The two copies differ only marginally within the coding regions but differ substantially in the respective intergenic regions. Both copies of the genes are coordinately expressed in cells grown aerobically on 2-aminobenzoate.

Aerobiosis↗
PubMed2001

Anaerobic metabolism of 3-hydroxybenzoate by the denitrifying bacterium Thauera aromatica.

The anaerobic metabolism of 3-hydroxybenzoate was studied in the denitrifying bacterium Thauera aromatica. Cells grown with this substrate were adapted to grow with benzoate but not with 4-hydroxybenzoate. Vice versa, 4-hydroxybenzoate-grown cells did not utilize 3-hydroxybenzoate. The first step in 3-hydroxybenzoate metabolism is a coenzyme A (CoA) thioester formation, which is catalyzed by an inducible 3-hydroxybenzoate-CoA ligase. The enzyme was purified and characterized. Further metabolism of 3-hydroxybenzoyl-CoA by cell extract required MgATP and was coupled to the oxidation of 2 mol of reduced viologen dyes per mol of substrate added. Purification of the 3-hydroxybenzoyl-CoA reducing enzyme revealed that this activity was due to benzoyl-CoA reductase, which reduced the 3-hydroxy analogue almost as efficiently as benzoyl-CoA. The further metabolism of the alicyclic dienoyl-CoA product containing the hydroxyl substitution obviously required additional specific enzymes. Comparison of the protein pattern of 3-hydroxybenzoate-grown cells with benzoate-grown cells revealed several 3-hydroxybenzoate-induced proteins; the N-terminal amino acid sequences of four induced proteins were determined and the corresponding genes were identified and sequenced. A cluster of six adjacent genes contained the genes for substrate-induced proteins 1 to 3; this cluster may not yet be complete. Protein 1 is a short-chain alcohol dehydrogenase. Protein 2 is a member of enoyl-CoA hydratase enzymes. Protein 3 was identified as 3-hydroxybenzoate-CoA ligase. Protein 4 is another member of the enoyl-CoA hydratases. In addition, three genes coding for enzymes of beta-oxidation were present. The anaerobic 3-hydroxybenzoate metabolism here obviously combines an enzyme (benzoyl-CoA reductase) and electron carrier (ferredoxin) of the general benzoyl-CoA pathway with enzymes specific for the 3-hydroxybenzoate pathway. This raises some questions concerning the regulation of both pathways.

Acyl Coenzyme A↗
PubMed2001

Reinvestigation of a new type of aerobic benzoate metabolism in the proteobacterium Azoarcus evansii.

The aerobic metabolism of benzoate in the proteobacterium Azoarcus evansii was reinvestigated. The known pathways leading to catechol or protocatechuate do not operate in this bacterium. The presumed degradation via 3-hydroxybenzoyl-coenzyme A (CoA) and gentisate could not be confirmed. The first committed step is the activation of benzoate to benzoyl-CoA by a specifically induced benzoate-CoA ligase (AMP forming). This enzyme was purified and shown to differ from an isoenzyme catalyzing the same reaction under anaerobic conditions. The second step postulated involves the hydroxylation of benzoyl-CoA to a so far unknown product by a novel benzoyl-CoA oxygenase, presumably a multicomponent enzyme system. An iron-sulfur flavoprotein, which may be a component of this system, was purified and characterized. The homodimeric enzyme had a native molecular mass of 98 kDa as determined by gel filtration and contained 0.72 mol flavin adenine dinucleotide (FAD), 10.4 to 18.4 mol of Fe, and 13.3 to 17.9 mol of acid-labile sulfur per mol of native protein, depending on the method of protein determination. This benzoate-induced enzyme catalyzed a benzoyl-CoA-, FAD-, and O2-dependent NADPH oxidation surprisingly without hydroxylation of the aromatic ring; however, H2O2 was formed. The gene (boxA, for benzoate oxidation) coding for this protein was cloned and sequenced. It coded for a protein of 46 kDa with two amino acid consensus sequences for two [4Fe-4S] centers at the N terminus. The deduced amino acid sequence showed homology with subunits of ferredoxin-NADP reductase, nitric oxide synthase, NADPH-cytochrome P450 reductase, and phenol hydroxylase. Upstream of the boxA gene, another gene, boxB, encoding a protein of 55 kDa was found. The boxB gene exhibited homology to open reading frames in various other bacteria which code for components of a putative aerobic phenylacetyl-CoA oxidizing system. The boxB gene product was one of at least five proteins induced when A. evansii was grown on benzoate.

Aerobiosis↗
PubMed2001

A randomized controlled clinical trial of zinc, vitamin A or both in undernourished children with persistent diarrhea in Bangladesh.

UNLABELLED: In a double-blind randomized controlled clinical trial, moderately malnourished Bangladeshi children (61-75% of the median weight/age) were studied for the effect of zinc and/or vitamin A supplementation on the clinical outcome of persistent diarrhea. Children 6 mo to 2 y of age with diarrhea for more than 14 d were randomly allocated into 4 groups of 24 receiving a multivitamin syrup and (i) zinc (20 mg elemental), (ii) vitamin A, (iii) both zinc and vitamin A, or (iv) neither, in 2 doses daily for 7 d. Clinical data on recovery and on stool output, consistency and frequency were recorded for 7 d, and weight change from day 1 to day 7 was assessed. The baseline characteristics of the four study groups were comparable. The mean daily stool outputs from days 2 to 7 of therapy were significantly less in the zinc and zinc plus vitamin A groups, but not in the vitamin A group, in comparison with the control group. In children receiving zinc, the cumulative stool weight in the 7 d was 39% less than in the control group (p < 0.001) and 32% less than in the vitamin A group (p = 0.006). The cumulative stool weight in the zinc plus vitamin A group was 24% less than in the control group (p < 0.001), but the 14% lower output than in the vitamin A group was not statistically different. The change in body weight over the 7 d study period was significantly different between the group receiving zinc and the control group (+111 g vs -90 g, p = 0.045). The rate of clinical recovery of children within 7 d was significantly greater in the zinc group (88%) compared with the control group (46%, p = 0.002) or vitamin A group (50%, p = 0.005), but not statistically different from the zinc plus vitamin A group (67%, p = 0.086). CONCLUSION: The results indicate that zinc, but not vitamin A, supplementation in persistent diarrhea reduces stool output, prevents weight loss and promotes earlier recovery.

Bangladesh↗