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Biomedical subjects

A Witkowski

Publications and source records attributed to A Witkowski.

At least 19 recordsLinked to original sources
PubMed2006

Changes in the activity of acid glycosidases during posthatch development and regression after light reduction of Japanese quail testes and epididymides.

In this study specific activities of four acid glycosidases: beta-N-acethylhexosaminidase (beta-HEX), beta-galactosidase (beta-GAL), alpha- and beta-mannosidase (alpha- and beta-MAN) were investigated in Japanese quail testes and epididymides during posthatch development and regression after light reduction. The specific activity of testicular beta-HEX and beta-GAL increased steadily during posthatch development and assumed maximum values for testes weighing 200-400 mg, when numerous spermatocytes appear in the testes of quail, and then decreased slowly. These enzymes showed much higher specific activity after 15 days of light reduction, and decreased to the control level after 30 days. Activity of alpha- and beta-MAN remained rather constant during testicular development and involution. The epididymal activity of the acid glycosidases was very low in immature individuals, whereas in sexually mature birds it was found to increase several-fold. Short photoperiod resulted in a decreased activity of these enzymes after 30 days to the values found in immature birds. A marked increase in the activity of acid glycosidases in the epididymides of sexually mature animals and a decrease in this activity during epididymidal regression indicate that these enzymes take part in reproductive processes. It is concluded that the activities of beta-HEX, beta-GAL, alpha- and beta-MAN in the development and regression of Japanese quail testes and epididymides change similarly as in mammals.

Acids↗
PubMed2006

Changes in the activity of soluble arylsulphatase during the post-hatch development and regression after light reduction of Japanese quail testes and epididymides.

This study demonstrates that specific activity of soluble arylsulphatase (AS) during post-hatch development of Japanese quail testes is the highest for testes weighing from 20 to 200mg, and then decreases as the weight of testes increases, while AS activity per g of wet tissue decreases steadily for testes weighing over 20 to 30 mg. Total AS activity showed a steady increase with the increasing weight of testes. The highest increments in the enzyme activity concerned testes weighing up to 30 mg and those weighing from 30 to 150 mg. Mature animals with testes weighing from 2 to 4 g showed an equal level of total AS activity. Based on this data it is suggested that the changes found in the enzyme activity concern mainly arylsulphatase from Sertoli cells. Specific activity of AS in epididymides remains low until testes reach a weight of approximately 1g and then increases, reaching maximal values for epididymides from the testes of sexually mature animals. Testicular and epididymal regression induced by a short photoperiod (6L:18D) after 30 days of the experiment increases AS activity in the testes and reduces its activity in the epididymides to the values found in the early stages of development. Testes and epididymides in the earliest stage of post-hatch development are characterized by an elution profile of AS in which the form of the enzyme bound to the strong anion exchanger at pH 6.0 is predominant, while in mature animals the form of the enzyme unbound to the anion exchanger predominates in the testes and epididymides. After 30-day regression of the testes and epididymides, the form bound to the anion exchanger did not increase, which suggests that the organs do not return exactly to the stage before sexual maturity.

Animals↗
PubMed2001

Clinical and angiographic performance of a new-generation modular stent design for treatment of de novo coronary lesions.

The objectives of the Race Car study were to assess the safety and efficacy of the Medtronic AVE S670 stent, a new-generation stent with a modular design consisting of interconnected sinusoidal rings allowing improved flexibility with good conformability and scaffolding. A total of 285 stents were implanted in 267 patients with (un)stable angina pectoris who underwent angioplasty of a single de novo lesion in a native coronary artery with a diameter between 3.0 and 4.0 mm. Available stent lengths were 9, 12, and 15 mm. The primary endpoint was the 6-month restenosis rate. Secondary endpoints were device and procedural success and major adverse cardiac event (MACE)-free survival at 1 and 6 months. All patients received the study stents and no other stents were used (angiographic success: 100%). Eight patients experienced a MACE during hospital admission (Q-wave MI in 2, non-Q-wave MI in 4, TLR in 2). A procedural success was obtained in 97% of the patients. There were no additional events at 1 month. The clinical endpoints encountered at 6 months were Q-wave MI in 1, bypass surgery in 3, and repeat angioplasty in 25 (MACE-free survival: 86.5%). Quantitative angiographic results were the minimum lumen diameter increased from 1.05 +/- 0.32 before to 2.73 +/- 0.39 mm after stent implantation. At follow-up, the loss in diameter was 0.74 +/- 0.50 mm. The loss index was 0.45 +/- 0.31 and restenosis rate was 13.4%. This study has demonstrated that the S670 stent in patients with (un)stable angina pectoris requiring intervention of a single lesion has a low acute and 6-month major event rate and a low angiographic restenosis rate.

Aged↗
PubMed2001

[Assessment of myocardial function at infarct zone after PTCA infarct-related artery--a study with tissue Doppler echocardiography].

UNLABELLED: Angioplasty of an infarct-related artery (IRA) performed several weeks or months after myocardial infarction (MI) may improve myocardial function. It is still unclear though, how soon wall function is restored following the procedure. This study was designed to assess quantitatively changes of regional left ventricular function after PTCA of IRA by means of tissue Doppler echocardiography (TDE). Thirty nine patients (30 male, mean age 53.4 +/- 8.4 yrs) who had MI 13 +/- 6 weeks earlier were qualified for IRA angioplasty on the basis of dobutamine stress echocardiography (DSE) if a viable myocardium was demonstrated. Regional wall function at infarct zone was assessed by TDE one day before PTCA (exam 1), 1-3 days (exam 2) and 28-30 days (exam 3) after successful angioplasty. Myocardial velocities and time--derived TDE intervals were calculated both in systole (systolic peak velocity--S, pre-ejection period--PEP, contraction time--CT), and diastole (E and A velocity waves, E/A ratio, isovolumic relaxation time--IVRT, rapid filling time--RFT, atrial filling time--AFT). All parameters were measured in longitudinal direction (annulus, basal and medial segments) of posterior (20 pts), anterior (17 pts) and lateral (2 pts) walls. S wave velocity increased between exam 1 and 2 (4.9 +/- 1.2 cm/s vs 5.6 +/- 1.3 cm/s, p < 0.02), whereas E wave decreased between examinations. Pre-PTCA E/A ratio was significantly lower than in exam 2 and 3. PEP decreased between exam 1 and 2 (96 +/- 23 ms vs 84 +/- 16 ms, p < 0.01). Significant correlation was found in IVRT and RFT prior and immediately after PTCA (103 +/- 21 ms vs 87 +/- 20 ms, p < 0.001, 151 +/- 39 ms, vs 170 +/- 30 ms p < 0.01 respectively). CONCLUSIONS: Patients after infarction with persisted viable myocardium may benefit from late angioplasty of IRA. In regional wall function assessment TDE seems to be more sensitive technique than visual wall motion analysis alone. TDE parameters demonstrated a rapid initial improvement. Changes of myocardial velocities (S, E) and time--derived TDE intervals (IVRT, PEP, RFT) are sensitive markers of restored myocardial function.

Adrenergic beta-Agonists↗
PubMed2000

Left ventricular outflow tract gradient decrease with non-surgical myocardial reduction improves exercise capacity in patients with hypertrophic obstructive cardiomyopathy.

OBJECTIVES: This study was undertaken to evaluate mid-term clinical results of non-surgical myocardial reduction in patients with hypertrophic obstructive cardiomyopathy. METHODS: Twenty-five patients with left ventricular outflow tract obstruction (mean gradient of 84. 54+/-31.38 mmHg) and symptoms of dyspnoea, angina and/or syncope were treated with non-surgical myocardial reduction. The patients were followed-up for a mean period of 10.44+/-1.8 months. In all patients clinical examination with echocardiography was repeated after every 3 months of follow-up, and a symptom-limited treadmill test was repeated at the 6 month follow-up. Eighteen patients underwent simultaneous respiratory gas analysis. RESULTS: Clinical follow-up examinations were achieved in all 25 patients. Persistent left ventricular outflow tract gradient reduction was seen in 23 patients. Seventeen patients had a reduction of left ventricular outflow tract gradient >50% of baseline value. Twenty patients showed a clinical improvement from 2.8+/-0.5 up to 1.2+/-0.5 NYHA class (P<0.001). The clinical improvement was matched by an improvement in objective measures of exercise capacity in patients with significant left ventricular outflow tract gradient reduction. Exercise time increased from 571.9+/-192.2 to 703.5+/-175.4 s, P<0. 001, and peak VO(2)increased from 14.6+/-5.2 to 20.5+/-8.6 ml. kg(-1)min(-1), P<0.05. CONCLUSION: Significant left ventricular outflow tract gradient reduction with exercise capacity improvement was achieved in the majority of patients treated with non-surgical myocardial reduction. We recommend this method as an alternative to surgery for symptomatic patients with hypertrophic obstructive cardiomyopathy.

Cardiac Catheterization↗
PubMed2000

A randomized comparison of elective high-pressure stenting with balloon angioplasty: six-month angiographic and two-year clinical follow-up. On behalf of AS (Angioplasty or Stent) trial investigators.

BACKGROUND: Previous randomized trials have shown beneficial effects of coronary stenting on restenosis and event-free survival rates. However, it has not yet been fully established if routine high-pressure stenting with an antiplatelet regimen can show similar results. METHODS: We compared the 6-month angiographic restenosis rate and 2-year event-free survival rate in 400 patients randomly assigned to stent or angioplasty. Aspirin and ticlopidine were prescribed in both groups. RESULTS: The procedural success rate did not significantly differ between the stent and angioplasty groups (97.92% vs 97.45%, P = not significant). No stent thrombosis was found. The 6-month restenosis rate was lower in the stent group (18. 18% vs 24.87%, P =.055). At 2 years target lesion revascularization rate was 17.19% in the stent group and 25.51% in the angioplasty group (P =.02, 33% reduction). No significant differences with regard to death and myocardial infarction were observed. Event-free survival rate at 6, 12, and 24 months was 86.77% vs 78.84%, 84.13% vs 76.70%, and 83.07% vs 73.54% for stent and angioplasty groups, respectively (P =.0172). CONCLUSIONS: The 6-month angiographic and 2-year clinical outcomes were better in patients who received stent than in those after balloon angioplasty. The difference in 2-year event-free survival rate was explained by a reduction in target lesion revascularization rate in the stent group.

Angioplasty, Balloon, Coronary↗
PubMed1999

Conversion of a beta-ketoacyl synthase to a malonyl decarboxylase by replacement of the active-site cysteine with glutamine.

beta-Ketoacyl synthases involved in the biosynthesis of fatty acids and polyketides exhibit extensive sequence similarity and share a common reaction mechanism, in which the carbanion participating in the condensation reaction is generated by decarboxylation of a malonyl or methylmalonyl moiety; normally, the decarboxylation step does not take place readily unless an acyl moiety is positioned on the active-site cysteine residue in readiness for the ensuing condensation reaction. Replacement of the cysteine nucleophile (Cys-161) with glutamine, in the beta-ketoacyl synthase domain of the multifunctional animal fatty acid synthase, completely inhibits the condensation reaction but increases the uncoupled rate of malonyl decarboxylation by more than 2 orders of magnitude. On the other hand, replacement with Ser, Ala, Asn, Gly, and Thr compromises the condensation reaction without having any marked effect on the decarboxylation reaction. The affinity of the beta-ketoacyl synthase for malonyl moieties, in the absence of acetyl moieties, is significantly increased in the Cys161Gln mutant compared to that in the wild type and is similar to that exhibited by the wild-type beta-ketoacyl synthase in the presence of an acetyl primer. These results, together with modeling studies of the Cys --> Gln mutant from the crystal structure of the Escherichia coli beta-ketoacyl synthase II enzyme, suggest that the side chain carbonyl group of the Gln-161 can mimic the carbonyl of the acyl moiety in the acyl-enzyme intermediate so that the mutant adopts a conformation analogous to that of the acyl-enzyme intermediate. Catalysis of the decarboxylation of malonyl-CoA requires the dimeric form of the Cys161Gln fatty acid synthase and involves prior transfer of the malonyl moiety from the CoA ester to the acyl carrier protein domain and subsequent release of the acetyl product by transfer back to a CoA acceptor. These results suggest that the role of the Cys --> Gln beta-ketoacyl synthases found in the loading domains of some modular polyketide synthases likely is to act as malonyl, or methylmalonyl, decarboxylases that provide a source of primer for the chain extension reactions catalyzed by associated modules containing fully competent beta-ketoacyl synthases.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗
PubMed1999

Dibromopropanone cross-linking of the phosphopantetheine and active-site cysteine thiols of the animal fatty acid synthase can occur both inter- and intrasubunit. Reevaluation of the side-by-side, antiparallel subunit model.

The objective of this study was to test a new model for the homodimeric animal FAS which implies that the condensation reaction can be catalyzed by the amino-terminal beta-ketoacyl synthase domain in cooperation with the penultimate carboxyl-terminal acyl carrier protein domain of either subunit. Treatment of animal fatty acid synthase dimers with dibromopropanone generates three new molecular species with decreased electrophoretic mobilities; none of these species are formed by fatty acid synthase mutant dimers lacking either the active-site cysteine of the beta-ketoacyl synthase domain (C161A) or the phosphopantetheine thiol of the acyl carrier protein domain (S2151A). A double affinity-labeling strategy was used to isolate dimers that carried one or both mutations on one or both subunits; the heterodimers were treated with dibromopropanone and analyzed by a combination of sodium dodecyl sulfate/polyacrylamide gel electrophoresis, Western blotting, gel filtration, and matrix-assisted laser desorption mass spectrometry. Thus the two slowest moving of these species, which accounted for 45 and 15% of the total, were identified as doubly and singly cross-linked dimers, respectively, whereas the fastest moving species, which accounted for 35% of the total, was identified as originating from internally cross-linked subunits. These results show that the two polypeptides of the fatty acid synthase are oriented such that head-to-tail contacts are formed both between and within subunits, and provide the first structural evidence in support of the new model.

Acetone↗
PubMed1999

Light and electron microscopic picture of atherosclerotic plaque in stable and unstable angina.

By presenting this series of 127 cases of coronary atherectomy the authors join the workers who study morphological differences between the atherosclerotic plaques in stable and unstable angina. Routine staining of formalin-fixed, paraffin-embedded material was completed by the detection of T lymphocytes, macrophages, mast cells, smooth myocytes and grown-in capillaries using monoclonal antibodies (DAKO), as well as by the immunofluorescent demonstration of fibrinogen in the plaques. The plaques derived from patients with unstable angina showed a higher incidence of mast cells (significant) and macrophages (insignificant). These cells render the plaque more susceptible to rupture or fissuring. There was also significantly more frequent and quantitatively more abundant permeation of the plaque by fibrinogen that raises the chance of thrombosis. These findings support the view that unstable angina correlates with the phenomena that favour the rupture of the plaque and thrombosis. Electron microscopy has not been used so far to study coronary atherosclerotic plaques. This material includes 15 plaques from stable and 18 plaques from unstable angina. A cover of fibrin and blood platelets is a regular formation on the surface and in the superficial layer of the plaque from unstable angina. It contributes to the "thrombotic proneness" of the coronary artery. These plaques also show abundant elastic fibres. This pattern corresponds to myo-elastic intimal hyperplasia ("intimal thickening") where the production of intimal elastin constitutes an essential phenomenon. Intimal thickening is interpreted as a preatherosclerotic event. The presence of elastin reflects an early stage of the development of the plaque. The plaque from stable angina shows abundant collagen fibres, which aggravate the lesion.

Adult↗
PubMed1999

[Usefulness of dobutamine stress echocardiography in qualification of patients to angioplasty of infarct related artery].

UNLABELLED: Late angioplasty of an infarct-related artery (IRA) performed weeks or months after myocardial infarction (MI) may restore blood flow in IRA and would result in improvement of regional wall motion. This study was designed to assess dobutamine stress echocardiography (DSE) in predicting the improvement of regional left ventricular (LV) function in patients after late PTCA of IRA. MATERIAL AND METHODS: 44 patients (36 M 8 F, mean age 54 +/- 7 year) who had a MI 15 +/- +/- 8 weeks earlier, were qualified to angioplasty of IRA when DSE showed the change in wall motion at the infarct zone--improved during low dose infusion (5-10 micrograms/kg/min) and/or worsened during a high dose dobutamine (up to 40 micrograms/kg/min). Regional wall motion was assessed by DSE performed at 2-7 days and 6-month after successful angioplasty. Wall motion score index (WMSI) decreased from 1.51 +/- 0.29 at rest to 1.31 +/- 0.28 at low-dose dobutamine infusion (p > 0.001) before angioplasty. Early after PTCA regional wall motion improves and baseline, exercise and rest values of WMSI decreased, compared with values before angioplasty. At baseline echocardiography 248 of segments were dyssynergic (112 hypokinetic, 125 akinetic and 10 dyskinetic). Viability during DSE was more frequent in segments with biphasic reaction during DSE than in segments showed monophasic reaction. In 34 patients control angiography (CA) was performed 6 month after successful PTCA. In this selected group CA showed significant restenosis of IRA in 12 pts (35% =, 9 of them showed positive DSE. Their base WMSI increased from 1.36 +/- 0.28 to 1.47 +/- 0.30 and peak stress WMSI from 1.32 +/- 0.29 to 1.60 +/- 0.30 (p < 0.001), respectively, between the exam just after PTCA comparing with the exam which detected restenosis. CONCLUSIONS: In some patients with infarction and a narrowed or occluded IRA the myocardium remains viable for a prolonged period. Improvement of wall motion during low-dose DSE and/or worsened during high dose DSE at infarct zone is a very useful tool in predicting of viable myocardium at infarct zone. DSE is an excellent method to demonstrate an immediate improvement in regional LV dysfunction after angioplasty of IRA. At 6 months' follow-up restenosis of IRA is often seen.

Angioplasty, Balloon, Coronary↗
PubMed1998

The malonyl/acetyltransferase and beta-ketoacyl synthase domains of the animal fatty acid synthase can cooperate with the acyl carrier protein domain of either subunit.

The active form of the animal fatty acid synthase (FAS) is a dimer of identical multifunctional polypeptides, each containing seven discrete functional domains, that cooperate to form two centers for palmitate synthesis. To assess the importance of domain cooperation across the subunit interface in the reaction mechanism, we have utilized a strategy based on complementation analysis in vitro of modified FASs carrying critical mutations in specific catalytic domains. Homodimeric FASs carrying the same mutation(s) in both subunits are unable to synthesize fatty acids. As predicted by the current head-to-tail model for the animal FAS, heterodimeric FASs formed between the acyl carrier protein (ACP) mutant and either the beta-ketoacyl synthase (KS) or malonyl/acetyltransferase (MAT) are active in palmitate synthesis, confirming that the KS and MAT domains can cooperate with the ACP domain of the opposite subunit. Contrary to this model however, heterodimeric FASs formed between the KS and MAT mutants, between a MAT, ACP double mutant, and a KS mutant, and between a KS, ACP double mutant, and a MAT mutant are also active in palmitate synthesis, indicating that the MAT and KS domains can also cooperate with the ACP domain of the same subunit. The results of this study reveal an unanticipated element of redundancy in the FAS reaction mechanism in that the amino-terminal KS and MAT domains can make functional contact with the penultimate carboxy-terminal ACP domain of either subunit. A revised model for the FAS is proposed in which the substrate loading and condensation reactions can be catalyzed either by one of the two subunits or by cooperation between domains across the subunit interface.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗
PubMed1998

High-Pressure Bail-out Coronary Stenting Without Anticoagulation: Early Outcome and Follow-up Results.

PURPOSE:The purpose of this study is to assess the immediate outcome and long-term results of high pressure bail-out coronary stenting without subsequent anticoagulation. PATIENTS AND METHODS: Between June 1994 and September 1996, 32 consecutive patients (males 24, mean age 55 +/- 9.3 years) underwent bail-out stenting at a mean deployment pressure of 15.5 +/- 2.3 mmHg because of complicated PTCA. A total of 54 stents (Palmaz-Schatz, Micro, Gianturco Roubin and Wiktor) were implanted, from one to four stents into each vessel. After the procedure all patients were treated with ticlopidine 500 mg/day and acetylosalicylic acid 300 mg/day only. RESULTS: Stents were successfully delivered in all patients. In the cath lab procedural success was 96.9%. During the in-hospital phase, there was one (3.1%) acute stent thrombosis followed by urgent bypass surgery (CABG). Four (12.5%) non-Q wave myocardial infarctions occurred. There were no subacute stent thrombosis or hemorrhagic complications. Six month angiographic restudy in 28 patients showed restenosis in 13 (46.4%): 9 patients were treated successfully by rePTCA. At one year 13 (40.6%) major adverse cardiac events occurred: eleven (34.4%) target lesion revascularizations (9 PTCA, 2 CABG), one (3.1%) elective CABG surgery and one (3.1%) late cardiac death. Event-free survival was 93.8% at one month, 65.6% at six months, and 59.4% at one year. CONCLUSIONS: High pressure bail-out coronary stenting with antiplatelet regimen is an effective and safe procedure for treating complicated PTCA. Although the restenosis rate is high, in most cases in-stent restenosis can be treated by rePTCA. In 60% of patients clinical course at one year was uneventful.

Journal Article↗
PubMed1997

Characterization of the interthiol acyltransferase reaction catalyzed by the beta-ketoacyl synthase domain of the animal fatty acid synthase.

The enzyme activity responsible for translocation of saturated acyl chains from the 4'-phosphopantetheine of the acyl carrier protein to the active site cysteine of the beta-ketoacyl synthase in the animal fatty acid synthase has been identified. An enzyme assay was devised that allows uncoupling of the interthiol transfer step from the condensation reaction. Experiments with various fatty acid synthase mutants indicate clearly that catalysis of the transfer of saturated acyl moieties from the 4'-phosphopantetheine thiol to the active site cysteine thiol, Cys-161, is an inherent property of the beta-ketoacyl synthase domain. Catalytic efficiency of the interthiol transferase increases from C2 to C12 and decreases with increasing chain-lengths beyond C12. Malonyl, beta-hydroxybutyryl, and crotonyl thioesters are not substrates for the transferase, whereas the beta-ketobutyryl moiety is a poor substrate. These features of the substrate specificity are exactly as predicted for a transferase that fulfills the proposed role in the fatty acid synthase reaction sequence and indicate that this activity plays an important role in determining the overall specificity of the beta-ketoacyl synthase reaction.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗
PubMed1997

Mapping of functional interactions between domains of the animal fatty acid synthase by mutant complementation in vitro.

Polypeptides of the animal fatty acid synthase (FAS) consist of three amino-terminal catalytic domains, beta-ketoacyl synthase, malonyl/acetyltransacylase, and dehydrase, separated by a 600-residue structural core from four carboxyl-terminal catalytic domains, enoyl reductase, beta-ketoacyl reductase, acyl carrier protein, and thioesterase. In the active dimeric form of the protein the two identical multifunctional polypeptides are oriented head-to-tail such that two sites for palmitate synthesis are formed at the subunit interface. In order to map the functional interactions between domains of the two subunits that contribute to the two sites of synthesis, we have utilized a strategy based on complementation analysis in vitro of modified FASs carrying mutations in specific catalytic domains. Homodimeric mutant FASs lacking functional beta-ketoacyl synthase (KS-), dehydrase (DH-), acyl carrier protein (ACP-), or thioesterase (TE-) domains, as well as heterodimers formed between ACP- and TE- subunits, between ACP- and DH- subunits, and between DH- and TE- subunits, were unable to synthesize fatty acids. However, heterodimers formed between KS- and either DH-, ACP-, or TE- subunits regained partial FAS activity. These data indicate that the dehydrase domain, although located in the amino-terminal half of the polypeptide, should be assigned to the complementation group located in the carboxy-terminal half that includes the acyl carrier protein and thioesterase domains. Thus, the current model for the animal FAS must be revised to reflect the finding that the two constituent polypeptides are not simply positioned side-by-side in a fully extended conformation but are coiled in a manner that allows the dehydrase domain to access the beta-hydroxyacyl-ACP located more than 1100 residues distant on the same subunit.

Animals↗