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Biomedical subjects

M Wojciechowski

Publications and source records attributed to M Wojciechowski.

At least 19 recordsLinked to original sources
PubMed2006

Ca(2+) -dependent plant response to Pb(2+) is regulated by LCT1.

Tobacco plants transformed with TaLCT1 were cultured on Knop's medium with modified calcium concentrations (0.01-3 mM) in the presence of Pb(2+), and in soil contaminated by lead. A 4-5 microM Pb(2+) administered in the presence of 1 mM Ca(2+) inhibited the root growth of transgenic plants to much lesser degree than of control plants, whereas in the presence of 3mM Ca(2+) no differences were found between the studied lines. The reduction of Pb(2+) toxicity in the presence of 1 mM Ca(2+) was not accompanied by a change in the lead tissue concentration. However, when Ca(2+) level in the medium was lowered to 0.01 mM, several fold higher root/shoot Pb ratio in transgenic plants was observed, twofold increase in the total amount of metal accumulated, and lower concentration of Pb in the xylem sap. Results suggest the involvement of TaLCT1 in the regulation of Ca-dependent Pb-detoxification, and under conditions of low calcium in lead uptake and distribution.

Biological Transport↗
PubMed2006

[Minimally invasive unicondylar knee replacement with computer navigation].

METHODS: From January 2003 to July 2005 a total of 50 St Georg medial knee monosleds with metal-backed tibial components in stably seated form and Uniglide prostheses (Alphanorm/Corin) with mobile bearing onlays were implanted in minimally invasive operations. Postoperatively the alignment-especially of the tibial components-was investigated, to check whether we had achieved the dorsal slope we had been aiming at, i.e. 5-7 degrees , in the region of these knee replacements. RESULTS: Before surgery there were initial malalignments of up to 10 degrees varus and 3 degrees valgus. All leg axes were restored to between -3 degrees and +3 degrees . The desired dorsal slope of 5-7 degrees for the knee monosleds relative to the tibial component was realized, the average slope being 5.3 degrees . The a-p alignment of the tibial component and of the femoral component was correct. CONCLUSIONS: Use of the navigation system leads to more accurate and reproducible results in terms of tibial dorsal slope, which is extremely important when these monosleds are used. Overcorrection of the leg axis is generally avoided. The use of too-high medial onlays is also reliably avoided by the navigation system's monitoring of the level of the cut.

Adult↗
PubMed2005

Thermodynamic and electrostatic properties of ternary Oxytricha nova TEBP-DNA complex.

Telomeres constitute the nucleoprotein ends of eukaryotic chromosomes which are essential for their proper function. Telomere end binding protein (TEBP) from Oxytricha nova was among the first telomeric proteins, which were well characterized biologically. TEBP consists of two protein subunits (alpha, beta) and forms a ternary complex with single stranded telomeric DNA containing tandem repeats TTTTGGGG. This work presents the characterization of the thermodynamic and electrostatic properties of this complex by computational chemistry methods (continuum Poisson-Boltzmann and solvent accessible surface calculations). Our calculations give a new insight into molecular properties of studied system. Based on the thermodynamic analysis we provide a rationale for the experimental observation that alpha and ssDNA forms a binary complex and the beta subunit joins alpha:ssDNA complex only after the latter is formed. Calculations of distribution of the molecular electrostatic potential for protein subunits alone and for all possible binary complexes revealed the important role of the "guiding funnel" potential generated by alpha:ssDNA complex. This potential may help the beta subunit to dock to the already formed alpha:DNA intermediate in highly steric and electrostatic favorable manner. Our pK(a) calculations of TEBP are able to explain the experimental mobility shifts of the complex in electrophoretic non-denaturating gels.

Algorithms↗
PubMed2003

Prediction of secondary ionization of the phosphate group in phosphotyrosine peptides.

A computational approach, based on a continuum molecular electrostatics model, for the calculation of the pK(a) values of secondary ionization of the phosphate group in phenyl phosphate derivatives is described. The method uses the ESP atomic charges of the mono-anionic and di-anionic forms of the ionizable phosphate group, computed with the use of the density functional method, and applies a new concept of the model group, being the reference state for the pK(a) calculations. Both conformational flexibility and tautomeric degrees of freedom are taken into account in the calculations. The method was parameterized using experimentally available pK(a) values of four derivatives of phenyl phosphates, and phosphotyrosine. Subsequently this parameterization was used to predict pK(a) of the phosphate group in a short peptide Gly-Gly-Tyr(P)-Ala, and in a longer peptide consisting of 12 residues, the latter in water, and in a complex with a protein-phospholipase. The agreement between the computed and the experimental pK(a) values is better than +/-0.3 pH units for the optimized solute dielectric constant of 11-13. This approach is promising and its extension to other phospho-amino acids is in progress.

Computer Simulation↗
PubMed2000

N3-oxoacyl derivatives of L-2,3-diaminopropanoic acid and their peptides; novel inhibitors of glucosamine-6-phosphate synthase.

Novel inhibitors 1-4 of glucosamine-6-phosphate synthase from Candida albicans have been designed based on acylation of the N3 amino group of L-2,3-diaminopropanoic acid with the corresponding ketoacids. These inhibitors have been shown to alkylate the fungal enzyme in a time-dependent manner. Compound 3 containing trans-beta-benzoyl acrylic acid as an acyl residue was found to be the most potent inhibitor in the series. Dipeptides composed of the active inhibitors and norvaline demonstrated potent antifungal activity against selected strains of Candida spp. and Saccharomyces cerevisiae. Their activity was reversed upon addition of N-acetylglucosamine to the medium.

Alkylation↗
PubMed1999

Modelling of insulin receptor tyrosine kinase in its active form: a case study for validation of theoretical methods.

An active form of an insulin receptor tyrosine kinase (IRK) catalytic core was modelled based on its experimentally known inactive form and the active form of a serine/threonine kinase, protein kinase A (PKA). This theoretical model was compared with the crystallographic structure of the active form of IRK reported later. The structures are very similar, which shows that all the most important features and interactions have been taken into account in the modelling procedure. The elaborated procedure can be applied to other tyrosine kinases. This would allow designing of a wide class of tyrosine kinase inhibitors, very important potential anti-cancer and/or anti-viral drugs.

Amino Acid Sequence↗
PubMed1997

Modelling of active forms of protein kinases: p38--a case study.

An active form of p38 protein kinase, belonging to the mitogen-activated protein kinases subfamily, has been designed based on crystallographically known structures of two other kinases, an active form of protein kinase A (PKA) and an inactive form of extracellular signal-regulated kinase 2 (ERK2). The modelling procedure is described. Its general scheme can also be applied to other kinases. The structure of the active forms of p38 and PKA is very similar in the region which binds the substrate. The ATP-binding mode is very similar in the active forms of all the three studied kinases. Models of the active forms allow for further studies on transphosphorylation processes at the molecular level, and modelling of inhibitors competitive with ATP and/or substrates.

Adenosine Triphosphate↗
PubMed1996

Constrained search of conformational hyperspace of inactivators of glucosamine-6-phosphate synthase.

Glucosamine-6-phosphate (GlcN-6-P) synthase (EC 2.6.1.16) is a key enzyme in amino sugar metabolism in micro-organisms and its selective and irreversible inhibitors can become valuable antifungal drugs. We performed a constrained search of the conformational hyperspace of glutamine and of the set of specific inactivators of the enzyme, as well as of some non-specific inhibitors of many cysteine containing enzymes. From these calculations we obtained spatial relationships of functional groups, the presence and specific orientation of which in the active site of the enzyme is important for effective and selective action of the inhibitor. Subsequent quantum chemical calculations confirmed the correctness of the pharmacophore conformation we obtained. Pharmacophore conformation of FMDP molecule, the most potent inhibitor in the selective inhibitors group, is placed close to the energy minimum on the conformational energy map.

Antifungal Agents↗
PubMed1995

Aerosolized furosemide in wheezy infants: a negative report.

We investigated the effects of 10 mg aerosolized furosemide on clinical score in 28 acutely wheezing infants (Part A) and in a second group of 20 intermittently wheezing babies on airway resistance and functional residual capacity during a symptomfree period (Part B), using a double-blind, placebo-controlled design. In both parts of the study no therapeutic effects were observed during and following aerosol inhalation of 10 mg furosemide.

Administration, Inhalation↗
PubMed1993

Assessment of metals in reconstituted metallothioneins by electrospray mass spectrometry.

A method has been developed that combines electrospray ionization mass spectrometry with pH control to provide analysis of metals in native or reconstituted metallothioneins. These metalloproteins cooperatively bind seven divalent metal ions, most commonly Zn2+ and Cd2+. Since the protein is denatured and metal ions are lost below pH3, the pH of the electrospray solution is critical to successful results. The metal-free apoprotein was detected with its most abundant ions in a charge state of 6+, while the folded metallothionein-metal complexes were observed with lower charge states. The retention of seven metals in the molecular ions detected is consistent with the hypothesis that metallothionein retains its conformation in the gas phase. This mass spectrometric technique can be used to determine rapidly and accurately how many and what cations are incorporated per molecule of protein. Information about molar distributions and estimates of relative abundances of various complexes in the sample can be acquired in a single measurement.

Amino Acid Sequence↗
PubMed1992

[The occurrence of hyena disease in young cattle].

Eight juvenile cattle with symptoms of hyena disease are described. This represents the first occurrence of the condition in the Republic of Poland. The growth of the affected animals was retarded, with a marked difference in longitudinal growth of the femoral, humeral, tibial and metatarsal bones. The animals showed altered nickel, manganese and inorganic phosphate concentrations, which may be related to the disease. The genetic studies did not reveal any aetiological factors.

Animals↗
PubMed1990

Aerosolized budesonide in asthmatic infants: a double blind study.

The efficacy of nebulized budesonide (0.5 mg b.i.d.) against placebo was evaluated in the management of asthma in 23 infants, aged 3 to 17 months, using a double blind crossover design. After an initial treatment period of 2 weeks placebo and budesonide were randomly administered during two consecutive treatment periods of 1 month. The progress of the patients was monitored using diary score cards, the number of salbutamol doses needed during the treatment periods, clinical examinations using standardized scoring cards, and registration of parents' preference period. Although there was a tendency toward fewer wheezing periods during budesonide, the results of the diary score cards were not significantly different between the budesonide period and the placebo period. The number of salbutamol doses used was also the same during both periods. Clinical examination after budesonide revealed less rhinitis and a less pathological lung auscultation, but the difference between the two periods was also not significant. Furthermore, the parents' preference could not distinguish between budesonide and placebo. We conclude that the trends in favor of nebulized budesonide are not significant and do not suggest that the suspension is effective in severe infantile asthma.

Administration, Intranasal↗
PubMed1986

Carotid artery disease: new criteria for evaluation by sonographic duplex scanning.

Use of established criteria in duplex sonographic screening for internal carotid artery disease resulted in low sensitivity (52%) and efficiency (82%). Analysis of duplex velocity data in 51 patients (102 vessels) led to the development of two new criteria for significantly diseased vessels: the ratio of the right to left peak systolic average velocities in the common carotid arteries (Vrcca/Vlcca) of less than 0.7 or greater than 1.3, and a peak systolic average velocity in the common carotid artery (Vcca) of less than 25 cm/sec. Addition of these criteria improved our sensitivity and efficiency to 95% and 94%, respectively.

Blood Flow Velocity↗
PubMed1986

[Börjeson-Forssman-Lehmann syndrome: report of a case].

We present a case of Börjeson-Forssman-Lehmann syndrome characterized by the presence of hypogonadism, grotesque facies, microcephaly, large ears, obesity and convulsions. In addition to these findings, which were detected also in the other patients described in the literature, the present patient showed hyperglycemia and aminoaciduria. In our opinion, the presence of these alterations and the poor evolution of the patient, with death occurring during the first year of life, may contribute to the amplification of the phenotypic spectrum of the Börjeson-Forssman-Lehmann syndrome.

Ear↗
PubMed1985

Prescribing: the power to set limits.

This paper discusses drawing up a restricted list of 245 drugs for use in an inner London group practice, based on a review of prescribing patterns in November 1982. The likely impact of the recent proposals by the Department of Health and Social Security to limit drugs available for prescription under the National Health Service on this project and on patient care is considered. We conclude that generic prescribing and a limited list of drugs may improve the quality of prescribing and be the only way to curb prescribing costs but that a limited list should be flexible, responsive to patients' needs, and applied to all prescribing. There should also be a mechanism for consumer feedback and regular revision of the list.

Attitude to Health↗
PubMed1984

Abnormal abdominal computerized tomography with amiodarone therapy and clinical significance.

Although the antiarrhythmic agent, amiodarone, is known to cause elevation of liver function tests, the effect of this drug on abdominal computerized tomography (CT) scans in patients on amiodarone therapy is unknown. Since iodine is in its molecular structure, the presence of amiodarone or its metabolites might be expected to produce higher CT numbers similar to the effect of contrast agents. To test this hypothesis, CT scans were performed in a series of 25 patients receiving amiodarone, 14 receiving short-term (mean 2.5 +/- 1.3 days) and 19 receiving long-term therapy (mean 130 +/- 75 days), as well as in a control group not receiving amiodarone. Gastrointestinal symptoms (if any) and liver function tests (LFT) prior to instituting amiodarone therapy and at the time of CT scan were also documented. CT scans showed a modestly increased density in multiple organs in the short-term group, but a markedly increased hepatic density in all but one patient in the long-term group. Presence of gastrointestinal symptoms or abnormal LFT did not appear to correlate with the CT number. Such findings would suggest that increased hepatic density on CT scan is to be expected in patients receiving long-term amiodarone therapy, and although the exact biologic pathways of amiodarone metabolism are uncertain, the liver appears to be a major site of drug storage and/or metabolism.

Adult↗