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Biomedical subjects

W Beck

Publications and source records attributed to W Beck.

At least 55 records · Page 3Linked to original sources
PubMed1993

Structural fluctuations between two conformational states of a transmembrane helical peptide are related to its channel-forming properties in planar lipid membranes.

Putative transmembrane helices of membrane proteins in general and channel proteins in particular often contain proline residues which may induce a bend into an otherwise regular helical structure. Here we show by fluorescence-energy-transfer measurements and molecular-dynamics calculations that, in the case of synthetic bilayer-spanning helical polypeptides, a proline-induced bend in a helix acts as a flexible element mediating rigid body motions of the helical segments. Most important, such structural fluctuations in the transmembrane helices seem to play a functional role in the formation of ionic channels in planar lipid bilayers and biological membranes.

Amino Acid Sequence↗
PubMed1993

Ornibactins--a new family of siderophores from Pseudomonas.

Novel linear hydroxamate/hydroxycarboxylate siderophores from strains of Pseudomonas cepacia were isolated and named ornibactins. The ornibactins represent modified tetrapeptide siderophores, possessing the sequence L-Orn1(N delta-OH, N delta-acyl)-D-threo-Asp(beta-OH)-L-Ser-L-Orn4(N delta-OH, N delta-formyl)-1,4-diaminobutane. The N delta-acyl groups of Orn1(N delta-OH, N delta-acyl) may vary and represent the three acids 3-hydroxybutanoic acid, 3-hydroxyhexanoic acid and 3-hydroxyoctanoic acid, leading to a mixture of three different ornibactins, designated according to their acyl chain length as ornibactin-C4, ornibactin-C6 and ornibactin-C8. Each of the siderophores is accompanied by a small amount of a more hydrophilic component with a 16 a.m.u. higher mass. The structure elucidation was based on results from gas chromatography amino acid analysis, electrospray mass spectrometry, and one- and two-dimensional nuclear magnetic resonance techniques.

Amino Acid Sequence↗
PubMed1993

Responsiveness of cardiac Na+ channels to a site-directed antiserum against the cytosolic linker between domains III and IV and their sensitivity to other modifying agents.

Elementary Na+ currents were recorded in inside-out patches from neonatal rat heart cardiocytes to analyze the influence of a site-directed polyclonal anti-serum against the linker region between the domains III and IV (amino acids 1489-1507 of the cardiac Na+ channel protein) on Na+ channel gating and to test whether this part of the alpha-subunit may be considered as a target for modifying agents such as the (-)-enantiomer of DPI 201-106. Anti-SLP 1 serum (directed against amino acids 1490-1507) evoked, usually within 10-15 min after cytosolic administration, modified Na+ channel activity. Antiserum-modified Na+ channels retain a single open state but leave, at -60 mV for example, their conducting configuration consistently with an about threefold lower rate than normal Na+ channels. Another outstanding property of noninactivating Na+ channels, enhanced burst activity, may be quite individually pronounced, a surprising result which is difficult to interpret in terms of structure-function relations. Removal of inactivation led to an increase of reconstructed peak INa (indicating a rise in NPo) and changed INa decay to obey second-order kinetics, i.e., open probability declined slowly but progressively during membrane depolarization. The underlying deactivation process is voltage dependent and responds to a positive voltage shift with a deceleration but may operate even at the same membrane potential with different rates. Iodate-modified Na+ channels exhibit very similar properties including a conserved conductance. They are likewise controlled by an efficient, voltage-dependent deactivation process.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

[Correlation between tyndallometry with the "laser flare cell meter" in vivo and biochemical protein determination in human aqueous humor].

INTRODUCTION: The laser flare-cell meter allows noninvasive measurement of aqueous flare in humans. In vitro studies have shown good correlations between flare values and albumin concentrations. In this study, we compared aqueous flare values and aqueous protein concentrations in living human eyes. PATIENTS AND METHODS: We measured aqueous flare and the total aqueous protein concentration in 52 eyes of 52 patients (age 58.4 +/- 18.8 years) that underwent cataract extraction (22 eyes) or trabeculectomy (30 eyes). Before surgery, aqueous flare was determined with the laser flare-cell meter (Kowa FC-1000). During surgery, 50 microliters of primary aqueous humor was aspired, and total aqueous protein concentration was performed using a modified Pierce-BCA assay. Linear regression analysis was calculated. RESULTS: There was a high correlation between aqueous flare values and total aqueous protein concentration (y = 0.52x + 0.15, r = 0.98, p < 0.00001). This correlation was observed both in eyes with and without cataract. CONCLUSION: Our results indicate that aqueous flare values as determined with the laser flare-cell meter reflect the true aqueous protein concentration quite accurately. Lens opacities appear not to significantly alter the results of aqueous flare measurements. As expected by theoretical assumptions, flare measurements overestimate aqueous protein concentrations in eyes with severely impaired blood-aqueous barriers because, according to Rayleigh's law, larger protein molecules cause more light scattering. However, transformation and expression of flare values as "albumin concentration equivalents" according to in vitro-calibration may still be useful, especially if the results of different instruments are to be compared.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Triple-dose versus standard-dose gadopentetate dimeglumine: a randomized study in 199 patients.

To investigate the safety, patient tolerance, and efficacy with 0.3 mmol/kg gadopentetate dimeglumine in magnetic resonance (MR) imaging of the central nervous system (CNS), a phase 3 trial was conducted in 199 patients with suspected CNS lesions. Patients received either 0.1 or 0.3 mmol/kg gadopentate dimeglumine (injection time, 15 seconds and 45 seconds, respectively). T1- and T2-weighted spin-echo sequences were performed at either 0.5 T or 1.5 T. In 80 patients with enhancing brain lesions, contrast-to-noise ratios (C/Ns) were calculated, and lesion-to-brain contrast was evaluated visually. Six patients (6%) in each dose group reported adverse events. Eight adverse events occurred with 0.1 mmol/kg and seven with 0.3 mmol/kg. Vital signs and laboratory values did not change significantly. C/N (P < .05) and visual assessment ratings were higher with 0.3 mmol/kg than with 0.1 mmol/kg. According to these preliminary results, 0.3 mmol/kg gadopentetate dimeglumine is safe and well tolerated when administered at approximately 1 mL/sec.

Adult↗
PubMed1992

Isolation and characterization of the three polypeptide components of 4-chlorobenzoate dehalogenase from Pseudomonas sp. strain CBS-3.

The three genes encoding the 4-chlorobenzene dehalogenase polypeptides were excised from a Pseudomonas sp. CBS-3 DNA fragment and separately cloned and expressed in Escherichia coli. The three enzymes were purified from the respective subclones by using an ammonium sulfate precipitation step followed by one or two column chromatographic steps. The 4-chlorobenzoate:coenzyme A ligase was found to be a homodimer (57-kDa subunit size), to require Mg2+ (Co2+ and Mn2+ are also activators) for activity, and to turn over MgATP (Km = 100 microM), coenzyme A (Km = 80 microM), and 4-chlorobenzoate (Km = 9 microM) at a rate of 30 s-1 at pH 7.5 and 25 degrees C. Benzoate, 4-bromobenzoate, 4-iodobenzoate, and 4-methylbenzoate were shown to be alternate substrates while 4-hydroxybenzoate, 4-aminobenzoate, 2-aminobenzoate, 2,3-dihydroxybenzoate, 4-coumarate, palmate, laurate, caproate, butyrate, and phenylacetate were not substrate active. The 4-chlorobenzoate-coenzyme A dehalogenase was found to be a homotetramer (30 kDa subunit size) to have a Km = 15 microM and kcat = 0.3 s-1 at pH 7.5 and 25 degrees C and to be catalytically inactive toward hydration of crotonyl-CoA, alpha-methylcrotonyl-CoA, and beta-methylcrotonyl-CoA. The 4-hydroxybenzoate-coenzyme A thioesterase was shown to be a homotetramer (16 kDa subunit size), to have a Km = 5 microM and kcat = 7 s-1 at pH 7.5 and 25 degrees C, and to also catalyze the hydrolyses of benzoyl-coenzyme A and 4-chlorobenzoate-coenzyme A. Acetyl-coenzyme A, hexanoyl-coenzyme A, and palmitoyl-coenzyme A were not hydrolyzed by the thioesterase.

Bacterial Proteins↗
PubMed1989

[Nedocromil sodium therapy in asthma patients. Therapeutic effect in addition to treatment with oral theophylline and inhaled bronchodilator agents].

131 asthmatics aged 12-65 years, who still had symptoms despite inhaled or oral bronchodilators, were included in this double-blind group comparative study involving nedocromil sodium (2 puffs of 2 mg each twice daily) and placebo (2 puffs twice daily). The study was carried out at 8 centers over six weeks. Under nedocromil sodium, cough, dyspnea and severity of attacks were reduced significantly. Overall patient assessment also clearly favoured the active substance. Nedocromil sodium was also superior to placebo in terms of the improvement of lung function (FEV1, FVC and PEFR). 26 patients complained of unusual symptoms (12 under nedocromil sodium, 14 under placebo). Nedocromil sodium proved to be an effective, safe and well-tolerated drug in the antiinflammatory long-term treatment of reversible obstructive airways disease.

Administration, Inhalation↗
PubMed1989

[A rare case of an epigastric fistula].

The authors report on a 75-year-old man who had been operated on 50 years before because of a gastric perforation. Since then he had had no symptoms. Two weeks before visiting the doctor he had noticed a 2-mm fistula in the epigastric region. Symptomatic therapy prescribed by the general practitioner had no result. On fistulography a complete gastric fistula was diagnosed. X-ray examination of the stomach showed an area highly suggestive of gastric cancer in the antrum region. Surgical examination revealed a 6-cm-long thread with concomitant, enormously extensive granuloma.

Aged↗
PubMed1988

The effect of L-asparaginase on lipid metabolism during induction chemotherapy of childhood lymphoblastic leukaemia.

L-asparaginase is an effective antileukaemic drug and a potent inhibitor of hepatic protein synthesis. Its effect on lipid metabolism was studied in two cohorts of children with ALL, one of whom received L-asparaginase concomitantly with three other drugs (protocol BFM 79). In the second protocol (BFM 83) administration of L-asparaginase was arranged to follow the other three drugs in time sequence. The two major findings of this study were elevated serum levels of total cholesterol and a strong increase in serum triglycerides. The former change was due to an increase in alpha-cholesterol and could not be attributed to L-asparaginase because it was also found following protocol BFM 83 before the administration of the drug. Elevations of total triglycerides were due to high levels of exogenous chylomicron bound triglycerides and were limited in occurrence almost exclusively to the period of L-asparaginase monotherapy. Hypothyroidism was excluded as a possible pathogenetic mechanism. These changes in lipid metabolism induced by L-asparaginase during intensive remission induction chemotherapy are fully reversible.

Adolescent↗
PubMed1987

Value of radiographic evidence of calcification of the aortic valve in adults with basal systolic ejection murmurs.

Severe aortic stenosis is an important, remediable and surgically correctable cause of symptoms and death. Diagnosis in adults and differentiation from minor degrees may be difficult. Aortic valve calcification visible on radiography or fluoroscopy is a sensitive but relatively nonspecific marker for the presence of critical aortic stenosis in patients with angina, dyspnoea or syncope. In 97% of patients with critical aortic stenosis analysed calcification was detected.

Adult↗