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Biomedical subjects

A Witkowski

Publications and source records attributed to A Witkowski.

At least 55 records · Page 3Linked to original sources

Joint Commission on Accreditation of Healthcare Organizations: standards and accreditation for durable medical equipment providers.

The accreditation survey for home medical equipment suppliers, as performed by the Joint Commission on Accreditation of Healthcare Organizations, emphasizes the process of care delivery, which includes equipment management and patient/caregiver instruction. Companies preparing for a survey are advised to perform a self-assessment to determine areas in need of review and improvement.

Accreditation↗

[Complex hemodynamic analysis of left ventricular systole in hypertrophic cardiopathy--clinical implications].

Hypertrophic cardiomyopathy is characterized by hemodynamic disturbances concerning left ventricular systole and diastole. Both of them are probably connected with abnormal structure of myocardium. The aim of the study was to assess left ventricular sufficiency, LV contractility and answer the question: if there is relationship between hemodynamic disturbances and clinical state. Estimation of verapamil influence on evaluated parameters was performed in the second part of the study. 20 patients (13 M, 7 F) aged 16-59 years (mean age 33, 25 yrs) with various type of hypertrophic cardiomyopathy were studied. Catheterization of the right and left heart and coronarography were performed in each patient. The first pressure derivative (d/P/dt) was recorded simultaneously with left ventricular pressure recording. Left ventricular angiography was performed in RAO 30 degrees and LAO 60 degrees projections. Analysis of the angiographic image of the whole heart cycle every 40 ms was performed to evaluate the changes in the left ventricular volume and LV wall thickness. Relationships between left ventricular pressure and volume were defined using computer PDP 11/24. To define verapamil influence, 6 patients received 10 mg of the drug intravenously, 14 patients received verapamil directly into left coronary artery 0.02 mg/kg of 0.5 mg/min. Control blood pressure measurements were performed after 5 and 10 minutes, and ventriculography after 15 min. Obtained results were compared with the control group consisted of 10 patients with normal hemodynamic data. Left ventricular contractility was estimated using V max and power/volume relationship (stress/volume). Both indices showed decreased left ventricular muscle contractility in hypertrophic cardiomyopathy. Verapamil had no significant effect on left ventricular contractility in our patients. Ejection period was studied using few indices. Ejection volume and net work (strokework) of the left ventricle were found to be decreased significantly, what means decreased mechanical preformance. The most significant were differences concerning mechanical performance which did not change after verapamil administration whereas circumferential fibre shortening velocity (VCF) was found to be decreased. If was probably related to increased afterload which could be caused by ventricular kinetics change. Midsystolic stress and the afterload index, significantly lower in cardiomyopathic patients. Preload was similar in both groups. Ejection indices of decreased afterload and normal preload proved decreased contractility. If above changes were primary, hypertrophy might be the compensating mechanism of decreased myocardial sufficiency in patients with hypertrophic cardiomyopathy. Which proved Hiroto's and Furabayashi's. The lack of negative effect verapamil on LV contractility in the group of our patients was very interesting, and could be partially related to beneficial effects in diastole.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

[Complex angioplasty (PTCA) in the treatment of coronary artery stenosis].

56 patients with more than one stenotic coronary artery were treated by complex PTCA with success rate of 96.4%. Complications occurred in 3.6% of pts. Restenoses were found in 9.4% of pts; only one of the dilated arteries were restenosed. 11.3% of pts had repeated PTCA, because of progression of stenosis in other than previously treated artery. Angina occurred earlier in pts with restenoses than in pts with progression of stenoses. Late efficacy (mean 19 months) of complex PTCA was high (90.7%).

Adult↗

Molecular cloning and sequencing of cDNAs encoding the entire rat fatty acid synthase.

Overlapping cloned cDNAs representing the entire sequence of the rat fatty acid synthase mRNA have been isolated from a cDNA library and sequenced. Authenticity of the cDNA clones was supported by hybridization to fatty acid synthase mRNA and by amino-terminal sequencing of 39 fatty acid synthase CNBr fragments. The full-length fatty acid synthase mRNA is 9156 nucleotides long and includes an 84-nucleotide 5' noncoding region, a 7515-nucleotide coding sequence, and a 1537-nucleotide 3' noncoding region; a second mRNA species containing a shortened 3' noncoding sequence is also transcribed in the rat. The encoded fatty acid synthase subunit contains 2505 amino acids and has a molecular weight of 272,340. Active sites and substrate binding sites were located within the sequence, thus establishing the order of domains on the multifunctional animal fatty acid synthase as condensing enzyme-transferase-dehydrase-enoyl reductase-ketoreductase-acyl carrier protein-thioesterase.

Amino Acid Sequence↗

[Angioplasty in acute and chronic occlusion of the coronary arteries].

An attempt of mechanical restoration of coronary artery patency and its angioplasty was carried out in 37 patients including 9 with acute myocardial infarction within 5 hours after the onset of an angina pain. The procedure was effective in 17 patients (45.9%), including 6 with acute myocardial infarction (66.7%). Mean time of a coronary artery occlusion was 5.1 weeks in the group with a good result in comparison with 17.2 weeks in the group with the unsuccessful procedure. In patients in whom restoration of a coronary artery patency was carried out within up to 3 months after its occlusion the procedure was effective in 64 per cent of them. Effectiveness of restoration of a coronary artery patency and its dilatation depends on the time from its occlusion to the procedure. The early attempt of the restoration of a coronary artery patency is effective in the majority of patients. In cases of the unsuccessful recanalization of a coronary artery occluded for a short time the main limitation of the procedure effectiveness was the vessel anatomy. The follow-up of 17 patients after a successful procedure showed restenosis or reocclussion in 6 of them (35%). It was referred in 1 case to the patient in whom restoration of a vessel patency was carried out during acute myocardial infarction (17%), and in 5 others to patients with a chronic occlusion of a coronary artery (45.5%).

Acute Disease↗

[Indices of left ventricular diastole in patients with unstable angina and angiographically documented collateral circulation].

23 patients (20 males, 3 females) aged 26-62 (mean 45.9 +/- 9.9) with unstable angina underwent the study to evaluate the effect of collateral circulation vessels (CCV) on left ventricular diastole. There was no evidence of myocardial infarction in the past and ejection fraction was normal (EF greater than 60%). At least one branch of left coronary artery was significantly stenosed (more than 75% of a vessel lumen). Patients were divided into two groups: group I -- with CCV, group II -- without CCV. Obtained data were compared between these groups and with the control group (K) consisted of 10 persons. CCV were only observed if a coronary artery was occluded or subtotally stenosed. When a coronary artery was occluded, CCV could prevent myocardial infarction. Time constant (T) prolongation (43.6 +/- 10.8 vs 32 58 +/- 7.9 ms, p less than 0.05 for groups I and K and 49.31 +/- 18.8 vs 32.58 +/- 7.9 ms, p less than 0.02 for groups II and K) testifies to relaxation slowing down in patients with unstable angina, which indicates left ventricular myocardial ischemia. Lack of CCV influence on time constant T (43.6 +/- 10.8 vs 49.31 +/- 18.8 ms, p less than 0.5) as well as remaining left ventricular diastolic parameters (EDVI, EDP) seems that CCV were an insufficient source of a blood flow to myocardium supplied by a stenosed artery.

Adult↗

Molecular cloning and sequencing of a cDNA encoding the thioesterase domain of the rat fatty acid synthetase.

A cloned cDNA containing the entire coding sequence for the long-chain S-acyl fatty acid synthetase thioester hydrolase (thioesterase I) component as well as the 3'-noncoding region of the fatty acid synthetase has been isolated using an expression vector and domain-specific antibodies. The coding region was assigned to the thioesterase I domain by identification of sequences coding for characterized peptide fragments, amino-terminal analysis of the isolated thioesterase I domain and the presence of the serine esterase active-site sequence motif. The thioesterase I domain is 306 amino acids long with a calculated molecular mass of 33,476 daltons; its DNA is flanked at the 5'-end by a region coding for the acyl carrier protein domain and at the 3'-end by a 1,537-base pairs-long noncoding sequence with a poly(A) tail. The thioesterase I domain exhibits a low, albeit discernible, homology with the discrete medium-chain S-acyl fatty acid synthetase thioester hydrolases (thioesterase II) from rat mammary gland and duck uropygial gland, suggesting a distant but common evolutionary ancestry for these proteins.

Amino Acid Sequence↗

Molecular cloning and sequencing of a cDNA encoding the acyl carrier protein and its flanking domains in the mammalian fatty acid synthetase.

Cloned cDNAs containing coding sequences for domains proximal to the carboxy terminus of the rat fatty acid synthetase have been isolated using an expression vector and domain-specific antibodies. The coding regions were assigned to specific domains of the multifunctional complex by identification of sequences coding for characterized peptide fragments and by recognition of sequences homologous to other monofunctional enzymes. Two clones contain the entire coding region for the acyl carrier protein domain. The sequence is flanked at the 3'-end by a region coding for the thioesterase domain and at the 5'-end by a sequence coding for a reductase, most likely the ketoreductase domain. Thus the ordering of these domain-coding regions in the fatty acid synthetase mRNA is established. The acyl carrier protein domain exhibits about 25% homology with that of the discrete monofunctional acyl carrier proteins of Escherichia coli, spinach and barley, the ketoreductase domain exhibits about 25% homology with bacterial dihydrofolate reductases and the active site of the thioesterase domain exhibits both primary and secondary structural features common to the serine proteases. These findings lend support to the hypothesis that the polyfunctional fatty acid synthetase probably arose by a complex evolutionary process involving fusion of genes coding for seven individual enzymes.

Acyl Carrier Protein↗

Interaction of rat mammary gland thioesterase II with fatty acid synthetase is dependent on the presence of acyl chains on the synthetase.

The interaction between rat mammary gland thioesterase II and fatty acid synthetase has been studied by a variety of physicochemical techniques. Pyrene-labeled thioesterase II does not exhibit increased fluorescence anisotropy when mixed with fatty acid synthetase, suggesting that the enzymes do not readily form a complex. Nevertheless, the functional interaction between the enzymes can be easily demonstrated by observing the hydrolysis, by unmodified thioesterase II, of acyl chains from their thioester linkage to the 4-phosphopantetheine of the fatty acid synthetase. This hydrolytic reaction is not inhibited even in the presence of a large excess of fatty acid synthetase with vacant 4'-phosphopantetheine thiols, indicating that interaction occurs only between thioesterase and fatty acid synthetase species which carry acyl chains on the 4'-phosphopantetheine thiols. A novel model system was devised which allowed us to explore the nature of the physical interaction between the two enzymes under conditions where the synthetase was actively engaged in acyl chain assembly. Fatty acid synthetase was treated with phenylmethanesulfonyl fluoride to inhibit its resident thioesterase activity, immobilized via a specific antibody to a column of Sepharose 4B, and exposed to the substrates required for acyl-enzyme assembly. When thioesterase II was introduced to the column, it passed through unretarded even though it efficiently catalyzed hydrolysis of the immobilized S-acyl synthetase en route. These results indicate that the two enzymes associate when an acyl chain is present on the synthetase and that they dissociate rapidly following completion of the catalytic process. Thus, the mammary system differs from that of the avian uropygial gland in which the two enzymes associate to form a stable complex even in the absence of substrates.

Animals↗

Pleiotropic effect of anticapsin on HeLa S3 cells.

Anticapsin, the terminal epoxyaminoacid moiety of tetaine, inhibits irreversibly growth of HeLa S3 cells. The antibiotic decreases to a similar extent incorporation of 3H-labelled precursors into nucleic acids and protein in intact cells: inhibition of protein synthesis prevails on prolonged incubation. Also incorporation of [3H]dTTP and [3H]UTP is inhibited in the presence of anticapsin into permeabilized cells. These effects, however, are not due to the interference with DNA or RNA polymerases since anticapsin only slightly suppresses RNA polymerase activity and has no effect on DNA polymerase in the cell-free systems. The results indicate that the mechanism of antiproliferative action of anticapsin in HeLa S3 cells differs from that of tetaine and imply that inhibition of protein synthesis might be the primary effect of anticapsin.

Alanine↗

Differential inhibition of DNA and RNA biosynthesis in HeLa S3 cells by tetaine, a dipeptide antibiotic.

A dipeptide antibiotic, tetaine, was found to diminish the rate of incorporation of 3H-labelled precursors into nucleic acids of intact and permeabilized HeLa S3 cells with concomitant negligible effect on protein synthesis. Comparison of the inhibitory effects of tetaine indicates that the antibiotic at 0.03-0.1 mM is a selective inhibitor of cellular DNA biosynthesis and, at higher concentration, of DNA and RNA biosynthesis. Tetaine is also an inhibitor of DNA and RNA polymerase reactions in a cell-free system, as determined using partially purified extracts from HeLa S3 cells that served as a source of the enzymes. The pretreatment experiments showed that tetaine inactivated the polymerases without affecting DNA template function. The tetaine effect on biosynthesis of nucleic acids in HeLa S3 cells can be attributed rather to the intact antibiotic than to the product of its enzymatic cleavage, anticapsin.

Alanine↗