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Biomedical subjects

R Bader

Publications and source records attributed to R Bader.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Ceramic acetabular cups for hip endoprostheses. 7: How do position of the center of rotation and the CCD angle of the shaft modify range of motion and impingement?].

The range of motion (ROM) of total hip prostheses is influenced by a number of parameters. An insufficient ROM may cause impingement, which may result in subluxation, dislocation or material failure of the prostheses. In a three-dimensional CAD simulation, the position of the centre of rotation and the CCD angle of the stem were investigated. Displacement of the centre of rotation of the femoral head may be due to wear (PE cups) or to the design of the prosthesis (ceramic cups). Stems of widely differing design have been developed and implanted. The results of the present study demonstrate that the ROM is clearly reduced by increasing penetration of the femoral head. At an inclination angle of 45 degrees, a depth of penetration of 2 mm restricts flexion by about 15 degrees, and a depth of penetration of 3 mm by about 30 degrees. At smaller angles of inclination the ROM is reduced and flexion and abduction are associated with an increased risk of impingement. With steeper acetabular cup inclinations, the risk of impingement decreases, but dislocation, the risk of rim fractures (ceramic cups), and wear and penetration rates (PE cups) increase. The CCD angle of the stem should be oriented to the anatomical situation. At high CCD angles (> 135 degrees), flexion is clearly limited, in particular when there is penetration of the femoral head. For modern total hip arthroplasty, prosthetic systems characterised by precise positioning of components, minimum wear, slightly recessed inserts, and appropriate CCD angles should be used.

Arthroplasty, Replacement, Hip↗
PubMed1999

Dermatologic surgery into the next millennium: Part I.

Dermatologic cosmetic surgery is a subspecialty of dermatology that has recently been developed. In this four-part series, we describe many of the procedures performed in our ambulatory surgery setting. We also highlight the significant changes in the techniques and treatment environments for these procedures over the past three decades. In part one, we focus on liposuction and face lift operations. Patients increasingly expect less invasive procedures, decreased "down time," and superior results. These expectations create a greater demand for the dermatologic surgeon. The trends and prospects for dermatologic cosmetic surgery in the next millennium are illustrated.

Esthetics↗
PubMed1998

Lifelong administration of high doses of ibandronate increases bone mass and maintains bone quality of lumbar vertebrae in rats.

As part of a long-term safety study the bisphosphonate ibandronate was investigated for its effects on bone quality in lumbar vertebrae in rats. Bone area, bone density and mechanical properties were assessed by peripheral quantitative computed tomography (pQCT), dual-energy X-ray absorptiometry (DXA) and compression tests. Female and male groups of Wistar rats received either vehicle or 3, 7 or 15 mg/kg per day of ibandronate over 104 weeks orally by gavage. Compared with the control group, bone mineral density, compressive strength and stiffness were significantly higher in ibandronate-treated animals, whereas no changes occurred in strain or modulus of elasticity. The increase in vertebral body stress was significant in some of the ibandronate-treated groups. The changes in mechanical properties appear to be due mainly to an increase in bone mass. A highly significant correlation was found between bone mineral density measured either by DXA (r = 0.86) or pQCT (r = 0.85) and maximal strength in vertebral bodies (p < 0.0001 each). In conclusion, we demonstrated that lifelong administration of doses of ibandronate far in excess of any therapeutically intended dose not only increases bone mass and apparent density, but also maintains or even slightly improves bone quality. Bone mineral density measured either by pQCT or DXA can be used as a predictor for ultimate strength in rat lumbar vertebral bodies after treatment with ibandronate.

Animals↗
PubMed1998

Inhibitor development and substitution therapy in a developing country: Turkey.

Prevalence of inhibitor in developing countries, such as Turkey, where fresh frozen plasma (FFP) is still in use due to high cost of concentrates, is unknown. To determine the frequency of inhibitors in Turkish haemophiliacs exposed to blood products, 53 haemophilia A patients (age range 1-20; median: 11 years) and 12 haemophilia B patients (age range 3-20; median: 10 years), were evaluated; 31 haemophilia A patients (23 severe) received plasma-derived concentrates and 22 patients (10 severe) only FFP. No haemophilia B patients developed inhibitor, compared with seven of 53 (13%) haemophilia A patients, all with a severe defect (7/33; 21%) and treated with concentrates (7/23; 30%), whereas severe patients treated with FFP showed a lower risk to develop inhibitors (0/10, P = 0.07). Inhibitors were detected after 8-125 exposure days (median: 52). Intermediate-purity concentrates and pasteurization seemed to be linked with a higher risk of inhibitor compared to high-purity concentrates and solvent-detergent inactivation for seven patients with inhibitor. In four of seven inhibitor patients low-dose concentrate was administered at 25 IU kg-1 twice weekly and inhibitor disappeared in 1-4 months. This regimen might be recommended for immune tolerance in developing countries for its lower cost.

Adolescent↗
PubMed1998

Inducer exclusion by glucose 6-phosphate in Escherichia coli.

The main mechanism causing catabolite repression by glucose and other carbon sources transported by the phosphotransferase system (PTS) in Escherichia coli involves dephosphorylation of enzyme IIA(Glc) as a result of transport and phosphorylation of PTS carbohydrates. Dephosphorylation of enzyme IIA(Glc) leads to 'inducer exclusion': inhibition of transport of a number of non-PTS carbon sources (e.g. lactose, glycerol), and reduced adenylate cyclase activity. In this paper, we show that the non-PTS carbon source glucose 6-phosphate can also cause inducer exclusion. Glucose 6-phosphate was shown to cause inhibition of transport of lactose and the non-metabolizable lactose analogue methyl-beta-D-thiogalactoside (TMG). Inhibition was absent in mutants that lacked enzyme IIA(Glc) or were insensitive to inducer exclusion because enzyme IIA(Glc) could not bind to the lactose carrier. Furthermore, we showed that glucose 6-phosphate caused dephosphorylation of enzyme IIA(Glc). In a mutant insensitive to enzyme IIA(Glc)-mediated inducer exclusion, catabolite repression by glucose 6-phosphate in lactose-induced cells was much weaker than that in the wild-type strain, showing that inducer exclusion is the most important mechanism contributing to catabolite repression in lactose-induced cells. We discuss an expanded model of enzyme IIA(Glc)-mediated catabolite repression which embodies repression by non-PTS carbon sources.

Biological Transport↗
PubMed1998

Limits to inducer exclusion: inhibition of the bacterial phosphotransferase system by glycerol kinase.

The uptake of methyl alpha-D-glucopyranoside by the phosphoenolpyruvate-dependent phosphotransferase system of Salmonella typhimurium could be inhibited by prior incubation of the cells with glycerol. Inhibition was only observed for glycerol preincubation times longer than 45 s and required the preinduction of both the glucose and the glycerol-catabolizing systems. Larger extents of inhibition by glycerol correlated with higher intracellular levels of glycerol kinase when the glp regulon had been induced to different extents. Preincubation with lactate did not inhibit methyl alpha-D-glucopyranoside uptake significantly, although both lactate and glycerol were oxidized by the cells. The cellular free-energy state of the cells (intracellular [ATP]/[ADP] ratio) was virtually identical for lactate and glycerol preincubation, suggesting that the inhibition of phosphotransferase-mediated uptake was not a metabolic effect. In vitro, phosphotransferase activity was inhibited to a maximal extent of 32% upon titrating cell-free extracts with high concentrations of commercial glycerol kinase. The results show that uptake systems that have hitherto been regarded merely as targets of the phosphotransferase system component IIA(Glc) also have the capacity themselves to retroinhibit the phosphotransferase system flux, presumably by sequestration of the available IIA(Glc), provided that these systems are induced to appropriate levels.

Adenosine Diphosphate↗
PubMed1998

Inducer exclusion in Escherichia coli by non-PTS substrates: the role of the PEP to pyruvate ratio in determining the phosphorylation state of enzyme IIAGlc.

The main mechanism causing catabolite repression in Escherichia coli is the dephosphorylation of enzyme IIAGlc, one of the enzymes of the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS). The PTS is involved in the uptake of a large number of carbohydrates that are phosphorylated during transport, phosphoenolpyruvate (PEP) being the phosphoryl donor. Dephosphorylation of enzyme IIAGlc causes inhibition of uptake of a number of non-PTS carbon sources, a process called inducer exclusion. In this paper, we show that dephosphorylation of enzyme IIAGlc is not only caused by the transport of PTS carbohydrates, as has always been thought, and that an additional mechanism causing dephosphorylation exists. Direct monitoring of the phosphorylation state of enzyme IIAGlc also showed that many carbohydrates that are not transported by the PTS caused dephosphorylation during growth. In the case of glucose 6-phosphate, it was shown that transport and the first metabolic step are not involved in the dephosphorylation of enzyme IIAGlc, but that later steps in the glycolysis are essential. Evidence is provided that the [PEP]-[pyruvate] ratio, the driving force for the phosphorylation of the PTS proteins, determines the phosphorylation state of enzyme IIAGlc. The implications of these new findings for our view on catabolite repression and inducer exclusion are discussed.

Bacterial Proteins↗
PubMed1997

BglF, the sensor of the E. coli bgl system, uses the same site to phosphorylate both a sugar and a regulatory protein.

The Escherichia coli BglF protein is a sugar permease that is a member of the phosphoenolpyruvate-dependent phosphotransferase system (PTS). It catalyses transport and phosphorylation of beta-glucosides. In addition to its ability to phosphorylate its sugar substrate, BglF has the unusual ability to phosphorylate and dephosphorylate the transcriptional regulator BglG according to beta-glucoside availability. By controlling the phosphorylation state of BglG, BglF controls the dimeric state of BglG and thus its ability to bind RNA and antiterminate transcription of the bgl operon. BglF has two phosphorylation sites. The first site accepts a phosphoryl group from the PTS protein HPr; the phosphoryl group is then transferred to the second phosphorylation site, which can deliver it to the sugar. We provide both in vitro and in vivo evidence that the same phosphorylation site on BglF, the second one, is in charge not only of sugar phosphorylation but also of BglG phosphorylation. Possible mechanisms that ensure correct phosphoryl delivery to the right entity, sugar or protein, depending on environmental conditions, are discussed.

Bacterial Proteins↗
PubMed1997

Escherichia coli is unable to produce pyrroloquinoline quinone (PQQ).

Many bacteria can synthesize the cofactor pyrroloquinoline quinone (PQQ), a cofactor of several dehydrogenases, including glucose dehydrogenase (GCD). Among the enteric bacteria, Klebsiella pneumoniae has been shown to contain the genes required for PQQ biosynthesis. Escherichia coli and Salmonella typhimurium were thought to be unable to synthesize PQQ but it has been reported that strain EF260, a derivative of E. coli FB8, can synthesize PQQ after mutation and can oxidize glucose to gluconate via the GCD/PQQ pathway (F. Biville, E. Turlin & F. Gasser, 1991, J Gen Microbiol 137, 1775-1782). We have re-investigated this claim and conclude that it is most likely erroneous. (i) Strain EF260, isolated originally by Biville and coworkers, was unable to synthesize a holo-enzyme GCD unless PQQ was supplied to the growth medium. No GCD activity could be detected in membrane fractions. (ii) The amount of PQQ detected in the growth medium of EF260 was very low and not very different from that found in a medium with its parent strain or in a medium containing no cells. (iii) EF260 cells were unable to produce gluconate from glucose via the PQQ/GCD pathway. (iv) Introduction of a gcd::Cm deletion in EF260, eliminating GCD, did not affect glucose metabolism. This suggested a pathway for glucose metabolism other than the PQQ/GCD pathway. (v) Glucose uptake and metabolism in EF260 involved a low-affinity transport system of unknown identity, followed most likely by phosphorylation via glucokinase. It is concluded that E. coli cannot synthesize PQQ and that it lacks genes required for PQQ biosynthesis.

Apoenzymes↗
PubMed1996

Cloning of the maoA gene that encodes aromatic amine oxidase of Escherichia coli W3350 and characterization of the overexpressed enzyme.

The mao operon of Escherichia coli W3350, which comprises the genes maoC and maoA, was cloned and appeared to be similar to that of Klebsiella aerogenes [Sugino, H., Sasaki, M., Azakami, H., Yamashita, M. & Murooka, Y. (1992) J. Bacteriol. 174, 2485-2492]. The gene that encodes aromatic amine oxidase (maoA) was isolated, sequenced, and expressed in E. coli TG2. The purified enzyme exhibited properties characteristic of a copper/topaquinone(TPQ)-containing amine oxidase with respect to the optical absorption and EPR spectra, the size of the subunits, and the optical absorption spectra obtained upon derivatization with hydrazines. However, high-resolution anion-exchange chromatography revealed that the preparation was heterogeneous. The enzyme preparation appeared to consist of at least four enzyme species with different specific activities, A474nm/A340nm ratios and TPQ/subunit ratios. Since the overall properties of the overexpressed enzyme and the authentic enzyme were similar and the separated enzyme species had identical N-terminal amino acid sequences, the heterogeneity does not seem to be caused by improper expression of the gene in the recombinant strain but by factors that interfere with the processing of the specific tyrosine in the precursor enzyme to functional TPQ. Although other causes cannot be excluded, the spectral data and TPQ/subunit ratios reported in the literature for other amine oxidases suggest that suboptimal synthesis of functional TPQ also occurs in other organisms.

Amino Acid Sequence↗
PubMed1994

Transcatheter oily chemoembolization for hepatocellular carcinoma. A 4-year study of 127 French patients.

BACKGROUND: In Western countries, only a small proportion of patients with hepatocellular carcinoma (HCC) can be treated with surgical resection. For other patients, locoregional management by transcatheter oily chemoembolization seems to be useful and warrants evaluation. METHODS: One hundred and twenty-seven French patients with an inoperable HCC were treated by transcatheter oily chemoembolization. The efficiency of the treatment was assessed by a comparison of this group with a group of 127 untreated patients. Each patient of the treated group was matched closely with an untreated patient for all the main clinical, anatomic, and biologic features that characterize the spontaneous evolution of HCC. RESULTS: The overall probabilities of survival in the treated group were 64%, 38%, 27%, and 27% at 1, 2, 3, and 4 years, respectively; those for the untreated group were 18%, 6%, and 5% at 1, 2 and 3 years, respectively (P < 0.0001). The survival was significantly increased in patients with Okuda Stage I and II disease (P < 0.0001), but not in those with Stage III. Karnofsky and Child-Pugh scores remained stable during the follow-up period and dropped only shortly before patients died. CONCLUSION: Transcatheter oily chemoembolization is an efficient treatment for unresectable HCC for the palliation of symptoms as well as for the prolongation of survival with a good quality of life.

Aged↗
PubMed1994

Microbes, enzymes and genes involved in dichloromethane utilization.

Dichloromethane (DCM) is efficiently utilized as a carbon and energy source by aerobic, Gram-negative, facultative methylotrophic bacteria. It also serves as a sole carbon and energy source for a nitrate-respiring Hyphomicrobium sp. and for a strictly anaerobic co-culture of a DCM-fermenting bacterium and an acetogen. The first step of DCM utilization by methylotrophs is catalyzed by DCM dehalogenase which, in a glutathione-dependent substitution reaction, forms inorganic chloride and S-chloromethyl glutathione. This unstable intermediate decomposes to glutathione, inorganic chloride and formaldehyde, a central metabolite of methylotrophic growth. Genetic studies on DCM utilization are beginning to shed some light on questions pertaining to the evolution of DCM dehalogenases and on the regulation of DCM dehalogenase expression. DCM dehalogenase belongs to the glutathione S-transferase supergene family. Analysis of the amino acid sequences of two bacterial DCM dehalogenases reveals 56% identity, and comparison of these sequences to those of glutathione S-transferases indicates a closer relationship to class Theta eukaryotic glutathione S-transferases than to a number of bacterial glutathione S-transferases whose sequences have recently become available. dcmA, the structural gene of the highly substrate-inducible DCM dehalogenase, is carried in most DCM utilizing methylotrophs on large plasmids. In Methylobacterium sp. DM4 its expression is governed by dcmR, a regulatory gene located upstream of dcmA, dcmR encodes a trans-acting factor which negatively controls DCM dehalogenase formation at the transcriptional level. Our working model thus assumes that the dcmR product is a repressor which, in the absence of DCM, binds to the promoter region of dcmA and thereby inhibits initiation of transcription.

Amino Acid Sequence↗
PubMed1994

Isolation and characterization of the Methylophilus sp. strain DM11 gene encoding dichloromethane dehalogenase/glutathione S-transferase.

The restricted facultative methylotroph Methylophilus sp. strain DM11 utilizes dichloromethane as the sole carbon and energy source. It differs from other dichloromethane-utilizing methylotrophs by faster growth on this substrate and by possession of a group B dichloromethane dehalogenase catalyzing dechlorination at a fivefold-higher rate than the group A enzymes of slow-growing strains. We isolated dcmA, the structural gene of the strain DM11 dichloromethane dehalogenase, to elucidate its relationship to the previously characterized dcmA gene of Methylobacterium sp. strain DM4, which encodes a group A enzyme. Nucleotide sequence determination of dcmA from strain DM11 predicts a protein of 267 amino acids, corresponding to a molecular mass of 31,197 Da. The 5' terminus of in vivo dcmA transcripts was determined by primer extension to be 70 bp upstream of the translation initiation codon. It was preceded by a putative promoter sequence with high resemblance to the Escherichia coli sigma 70 consensus promoter sequence. dcmA and 130 bp of its upstream sequence were brought under control of the tac promoter and expressed in E. coli to approximately 20% of the total cellular protein by induction with isopropylthiogalactopyranoside (IPTG) and growth at 25 degrees C. Expression at 37 degrees C led to massive formation of inclusion bodies. Comparison of the strain DM11 and strain DM4 dichloromethane dehalogenase sequences revealed 59% identity at the DNA level and 56% identity at the protein level, thus indicating an ancient divergence of the two enzymes. Both dehalogenases are more closely related to eukaryotic class theta glutathione S-transferases than to a number of bacterial glutathione S-transferases.

Amino Acid Sequence↗
PubMed1994

Multicentric evaluation of a new PT reagent based on recombinant human tissue factor and synthetic phospholipids.

A new PT reagent based on recombinant human tissue factor and synthetic phospholipids (phosphatidyl choline and phosphatidyl serine) with defined fatty acid side chains was calibrated against BCT/253 and CRM 149R. A small but consistent bias in the International Sensitivity Index (ISI) value was obtained using either the human or rabbit brain reference material. ISI values were around 1.0 or slightly lower depending on the respective instrument. Mixing studies with factor deficient plasmas showed a high factor sensitivity especially for factor VII as compared to commercial rabbit brain or human placenta thromboplastin. In an international field trial the reagent was tested using fully or semi automated Electra coagulometers in 4 different laboratories. Results with normal samples were in excellent agreement among the different laboratories. Mean values were 10.9, 10.9, 11.0, 11.2 s with a range of 9.5 to 12.5 s. Results of males and females were not different. In patients with liver disease very similar PT activities were found as compared to sensitive rabbit brain or human placental thromboplastins. In normals and patients with oral anticoagulation INR values correlated very well against BCT (r = 0.98, regression line y = -0.07 + 0.9 x). The distribution of samples was linear over the whole range. In the comparison against sensitive rabbit brain thromboplastin or human placental thromboplastin similar correlations were found. In a few cases higher INR values were observed for the recombinant reagent especially in patients with intensive treatment. Factor assays in those patients showed at least the strong reduction of one vitamin K-dependent coagulation factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Stimulation of bone marrow by administration of excessive doses of recombinant human erythropoietin.

Recombinant human erythropoietin (rhEPO) was administered intravenously to Beagle dogs in daily doses of 100, 500 and 3000 units/kg/day for 3 months. The high dose was more than 200-fold the therapeutic human maintenance dose. Such excessive rhEPO doses elicited extreme erythropoiesis. There was a dose-dependent stimulation of bone marrow fibroblasts, leading to bone marrow fibrosis in some of the high dose animals. The extent of myelofibrosis was intra- and interindividually different in various bones. Sternebrae proved to be practical for morphometric studies. The point-counting method was used for measurement. The portion of fatty tissue, sinusoids and fibrous tissue in the medullary space as well as the number of blood vessels and megakaryocytes were calculated. Such experimental conditions are not of relevance in human patients whose rhEPO therapy is interrupted as soon as their PCV reaches 35 vol%. Experimentally induced myelofibrosis should therefore not be considered as a risk in patients receiving therapeutic doses of rhEPO.

Adipose Tissue↗