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Biomedical subjects

J Meyer

Publications and source records attributed to J Meyer.

At least 19 recordsLinked to original sources

Classification of morphologic effects of percutaneous transluminal coronary angioplasty assessed by intravascular ultrasound.

The aim of this study was the assessment and classification of the morphologic effects of percutaneous transluminal angioplasty (PTCA) by intravascular ultrasound (IU). Fifty-eight patients were examined immediately after PTCA with a 4.8Fr, 20 MHz rotational tip IU system. In 10 patients (17%), IU images could not be analyzed due to failure of the imaging system or poor image quality. In 48 patients (83%; 40 men and 8 women, aged 55 +/- 9 years), IU images of 48 PTCA segments, as well as 41 distal and 44 proximal sites, were analyzed. The left anterior descending artery was studied in 30 patients, the right coronary artery in 17 and the left main coronary artery in 1. Calcium was present in 32 of 48 PTCA segments (67%). Plaque morphology was concentric in 18 patients (38%) and eccentric in 30 (62%). Seven distinct morphologic patterns were observed. In concentric plaques, plaque compression without significant wall alterations (type 1) was found in 2 patients (4%), superficial tears within the plaque (type 2) in 1 (2%) and deep tears (type 3) in 8 (17%). Deep tearing associated with submedial or subintimal dissection (type 4) was found in 2 patients (4%). Dissection between plaque and vessel wall without noticeable intimal tearing (type 5) was the most common morphology (n = 15; 31%) and occurred in concentric and eccentric plaques. In eccentric plaques, no significant tearing of the plaque (type 6) was found in 6 patients (13%), and tearing of the plaque close to its base with dissection (type 7) in 14 (29%).(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon, Coronary

Comparative binding of etretinate and acitretin to plasma proteins and erythrocytes.

The interactions of etretinate and its main metabolite acitretin with human plasma proteins have been investigated in vitro by an erythrocyte partitioning technique that allows a quantitative estimation of the plasma and erythrocyte binding. Etretinate was extensively lipoprotein-bound (75% of plasma etretinate), with a binding constant for its main low density lipoprotein carrier of 40 x 10(6) M-1, accounting for 48% of the total plasma-bound drug. Acitretin was mainly albumin-bound (91% of plasma acitretin), with a binding constant of 0.7 x 10(6) M-1. The total plasma binding of both drugs was > 99% and, in blood, the fractions associated with erythrocytes were 14.5 and 8.1% of the total amount for etretinate and acitretin, respectively.

Acitretin

[Coronary vascular stent implantation--experiences with the first 100 implants].

Coronary stent implantation was performed for blocking elastin recoil, reducing acute complications and restenosis. In 89 (95%) of 91 patients successful stent implantation was possible. No stent embolization occurred. Coronary luminal diameter measured 1.05 +/- 0.57 before PTCA and 1.9 +/- 0.2 mm post PTCA. After stent implantation mean diameter of the coronary artery measured 3.05 +/- 0.2 mm, with a balloon diameter of 3.0. Thus, elastic recoil is nearly completely blocked. In 28 (31%) of 91 patients stent implantation was performed for acute symptomatic dissection in 27 patients and occlusion in one patient. Stent delivery was successful in all. There was no acute occlusion, one acute thrombosis which could be treated with urokinase, no Q-wave-infarct, 4 (14%) non-Q-wave-infarcts and 14 (20%) CK-elevations without ECG changes. Coronary bypass surgery was necessary in 2 patients on an elective base during follow-up. In 72 (90%) of 80 patients follow-up coronary angiograms after 4 to 6 months were performed. Restenosis rate measured 21% overall, 14% for single stent, 60% for multiple stent implantation, and 14% in bail-out situations. Subacute thrombosis occurred in 10 (12%) of 89 patients, 7 (70%) of 10 events after bail-out stenting. Recanalization by thrombolytic and/or PTCA was possible in 9/10 patients. By improving monitoring of anticoagulation, the subacute thrombosis rate could be reduced to 3% even in bail-out situations. Bleeding complication occurred in 10% of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Cloning, sequencing and expression in Escherichia coli of the rubredoxin gene from Clostridium pasteurianum.

A 3.9 kb BglII-HindIII DNA fragment containing the rubredoxin gene from Clostridium pasteurianum has been cloned using oligonucleotide probes designed from the protein sequence. The 2675 bp SspI-HindIII portion of this fragment has been sequenced and found to contain three open reading frames in addition to the rubredoxin gene. The putative product of one of these open reading frames is similar to various thioredoxin reductases. The rubredoxin gene translates into a sequence that differs from the previously published protein sequence in three positions, D-14, D-22 and E-48 being replaced by the corresponding amides. These changes have been confirmed by partial resequencing of the protein. Promoter-like sequences and a transcription termination signal have been found near the sequence of the rubredoxin gene, which may therefore constitute an independent transcriptional unit. Expression of C. pasteurianum rubredoxin in Escherichia coli strain JM109 has been optimized by subcloning a 476 bp SspI-SspI fragment encompassing the rubredoxin gene. Under these conditions, the latter gene was partly under the control of the lac promoter of pUC18, and the level of rubredoxin production could be increased twofold on addition of a lactose analogue, thus reaching 2-3 mg of pure protein/l of culture. Recombinant rubredoxin was produced in E. coli cells as the holoprotein, and displayed a u.v.-visible-absorption spectrum identical with that of the rubredoxin purified from C. pasteurianum. M.s. and N-terminal sequencing showed that C. pasteurianum rubredoxin expressed in E. coli differs from its native counterpart by having an unblocked N-terminal methionine.

Amino Acid Sequence

Percutaneous transluminal coronary rotary ablation with Rotablator (European experience).

This study reports the results from 3 European centers using rotary ablation with Rotablator, a device that is inserted into the coronary artery and removes atheroma by grinding it into millions of tiny fragments. Rotary ablation was performed in 129 patients. Primary success (reduction in percent luminal narrowing greater than 20%, residual stenosis less than 50%, without complications) was achieved by rotary angioplasty alone in 73 patients (57%). An additional 38 patients (29%) had successful adjunctive balloon angioplasty. Thus primary success was achieved in 111 patients (86%) at the end of the procedure. Acute occlusion occurred in 10 patients (7.7%). Recanalization was achieved by balloon angioplasty in 7: urgent bypass grafting was undertaken in 2. Q-wave and non-Q-wave myocardial infarction occurred in 3 and 7 patients, respectively. No deaths occurred. Follow-up angiography was performed in 74 patients (60%). Restenosis, defined as the recurrence of significant luminal narrowing (greater than 50%) occurred in 17 of 37 patients (46%) who underwent rotary ablation alone, and 11 of 37 patients (30%) who had adjunctive balloon angioplasty. The overall angiographic restenosis rate was 37.8%. In conclusion, rotary ablation is technically feasible, and relatively safe in the coronary circulation. The low primary success rate reflects the limited size of the device, which can be introduced through available guiding catheters, and limits the use of rotary ablation as a stand-alone procedure to lesions in small arteries or in distal locations. No reduction in restenosis was seen, but the role of this device combined with balloon angioplasty in larger arteries needs to be further defined.

Adult

Echocardiographic and angiographic evaluation of left ventricular function during percutaneous transluminal aortic valvuloplasty.

Transesophageal echocardiography was used to study the effect of the balloon inflation on left ventricular function in 20 patients with critical aortic stenosis undergoing balloon valvuloplasty. Balloon inflation caused an increase of end-diastolic (15% to 34%) and end-systolic (57% to 72%) left ventricular volume. Left ventricular wall stress increased from 30 +/- 10 x 10(3) dyn/cm2 at diastole and 121 +/- 40 x 10(3) dyn/cm2 at systole to 44 +/- 11 x 10(3) dyn/cm2 and 191 +/- 55 x 10(3) dyn/cm2, respectively, when the balloon was inflated (P less than 0.05). Turbulent regurgitant jet across the mitral valve increased from 15 +/- 2% to 25 +/- 3% during balloon inflation (P less than 0.01). Continued monitoring of left ventricular function after balloon deflation demonstrated prolonged enlargement of left ventricular volumes. Our data show that balloon inflation causes an increase of left ventricular volume and impairment of contraction. Increase of left ventricular wall stress--associated with a reduction of coronary blood flow, due to lower aortic pressure--could result in ischemic myocardial injury.

Aged

High-speed rotational angioplasty-induced echo contrast in vivo and in vitro optical analysis.

High-speed rotational angioplasty is being evaluated as an alternative interventional device for the endovascular treatment of chronic coronary occlusions. It has been postulated that this type of angioplasty device may produce particulate debris or cavitations that induce myocardial ischemia. To determine the clinical presence of myocardial ischemia during rotational angioplasty, echocardiographic monitoring for wall motion abnormalities was performed in 9 patients undergoing rotational atheroablation using the Auth Rotablator for 10-sec intervals at 150,000 and 170,000 rpm. No wall motion abnormalities were detected in 5 patients evaluated with transesophageal echocardiography or in 4 patients monitored transthoracically, although AV block developed in one patient. Video intensitometry of the myocardial contrast effect for rotation times ranging from 3 to 20 sec found transient contrast enhancement of the myocardium supplied by the treated vessel. Intensity varied over time with half-time decay between 5.6 and 40 sec, indicating the likelihood of microcavitation. An in vitro model was constructed to measure the cavitation potential of the Auth Rotablator. A burr of 1.25 mm diameter rotating at 160,000 rpm achieves a velocity in excess of the 14.7 m/sec critical cavitation velocity. Testing the device in fresh human blood and distilled water produced microcavitations responsible for the enhanced echo effect, with the intensity and longevity of cavitation more pronounced in blood and proportional to the rotation time and speed. The mean size of the microcavitation bubbles in water was 90 +/- 33 (52-145) microns measured from photographs taken with a copper vapour laser emitting light pulses of 50 nsec duration as light source. The mean velocity of bubbles was found to be 0.62 +/- 0.30 ranging from 0.23 to 1.04 m/sec. It was measured via the motion of the bubbles during 5 laser pulses within 800 nsec. Clearly, microcavitations are associated with enhanced myocardial echo contrast effect.

Angioplasty, Balloon, Coronary

Recombination of constant and variable modules alters DNA sequence recognition by type IC restriction-modification enzymes.

EcoR124 and EcoDXXI are allelic type I restriction-modification (R-M) systems whose specificity genes consist of common structural elements: two variable regions are separated by a constant, homologous region containing a number of repetitive sequence elements. In vitro recombination of variable and constant elements has led to fully active, hybrid R-M systems exhibiting new and predictable target site specificities. Methylation of synthetic DNA sequences with purified, hybrid modification methylases was used to confirm the proposed recognition sequences. The results clearly demonstrate the correlation between protein domains and target site specificity. Our data suggest that a bacterial population may switch the recognition sequences of its type I R-M system by single recombination events and thus is able to maintain a prokaryotic analogue of the immune system of variable specificity.

Base Sequence

Dietary restriction of calcium, phosphorus, and vitamin D elicits differential regulation of the mRNAs for avian intestinal calbindin-D28k and the 1,25-dihydroxyvitamin D3 receptor.

We investigated the regulation of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-induced calbindin-D28k (CaBP) and of the vitamin D receptor (VDR) by evaluating CaBP protein, CaBP mRNA, and VDR mRNA under conditions of altered intake of vitamin D, calcium, or phosphorus. Chickens were maintained for 10 days on one of four diets: vitamin D-deficient, normal (1.0% Ca and 1.1% P), low calcium (0.1% Ca and 1.2% P), and low phosphorus (1.1% Ca and 0.3% P). CaBP was undetectable in D-deficient duodena and was elevated above normal values by low-calcium (3.1-fold) and low-phosphorus (2.3-fold) intake. Contradictory to published data, we observed a correlation between CaBP protein and mRNA levels in that the CaBP mRNA was absent in D-deficient intestine and augmented threefold and twofold in low-calcium and low-phosphate duodena, respectively. In contrast, VDR mRNA concentrations were identical in vitamin D-deficient and normal duodena, implying that intestinal VDR is not dependent upon 1,25-(OH)2D3 for basal expression. Chickens fed a low-phosphorus diet displayed a twofold increase in VDR mRNA, but those fed a low-calcium diet exhibited a dramatic decrease in VDR mRNA. These data show that CaBP mRNA and protein levels are modulated in a tightly coupled fashion, and they are consistent with previous conclusions that augmented circulating 1,25-(OH)2D3 stimulates CaBP expression when dietary calcium or phosphorus is limiting. However, a more complex regulation of VDR expression occurs in that low-phosphorus restriction enhances VDR mRNA levels, possibly via increased circulating 1,25-(OH)2D3. Conversely, reduced dietary calcium diminishes VDR mRNA despite increased circulating 1,25-(OH)2D3, indicating that another factor, such as parathyroid hormone, is a predominant downregulator of VDR.

Animals

Synergistic platelet inhibitory effect of the phosphodiesterase inhibitor piroximone and iloprost.

Platelet activity is regulated through synthesis and degradation of the intracellular second messengers cAMP or cGMP. The antiplatelet effect of the phosphodiesterase (PDE) III inhibitor Piroximone (PIR) was studied in vitro in platelet rich plasma. ADP induced aggregation was inhibited by PIR with an IC50 of 67 +/- 43 microM. The inhibitory effect was time and dose dependent. The antiaggregatory effects in vivo were studied in anaesthetised rats. Reduction of platelet count following injection of 100 micrograms/kg bw collagen was measured after bolus injection of PIR and vehicle. Piroximone bolus 2 mg/kg bw resulted in a 50% inhibition of platelet aggregation in rats. Cyclic AMP levels in washed platelets rose time and dose dependently after PIR. Coincubation of PDE III inhibitor PIR and adenylate cyclase activator Iloprost (ILO) resulted in a significant synergistic enhancement of the antiaggregatory effect. The PDE III inhibitor PIR exerted an effective inhibition of platelet aggregation in vivo and in vitro. The inhibitory effects in vitro were synergistically augmented by the prostacyclin analog Iloprost. These platelet inhibitory effects might be of clinical importance.

Adenosine Diphosphate

Receptor binding properties of the new and specific thromboxane receptor antagonist Bay U 3405.

Human platelet membranes were used to characterize the receptor binding properties of the specific thromboxane receptor antagonist 3H-SQ 29548 and the displacement of 3H-SQ 29548 from its binding site by the new thromboxane receptor antagonist Bay u 3405. The specific binding of 3H-SQ 29548 was saturable with an association rate constant of 1 x 10(-11) mol-1 min-1 and a dissociation rate constant of 0.032 min-1. Nonspecific binding of 3H-SQ 29548 was below 10%. When Scatchard plot analysis was performed on equilibrium saturation binding the kD was 69 nmol/l and the Bmax was calculated as 3.9 pmol/mg membrane protein. 3H-SQ 29548 was dose dependently displaced from its binding site by addition of increasing concentrations of Bay u 3405 yielding an IC50 value of 68 +/- 12 nmol/l, being not significantly different from the IC50 of nonlabelled SQ 29548 (38 +/- 13 nmol/l). The results show that Bay u 3405 is a potent and specific thromboxane receptor antagonist, displacing 3H-SQ 29548 from its binding site on human platelet membranes with IC50 values being not significantly different. These receptor binding properties and the long biological half life reported in vivo make Bay u 3405 a promissing compound for the treatment of human cardiovascular diseases.

Binding, Competitive

Increase in endogenous fibrinolysis and platelet activity during exercise in young volunteers.

The influence of physical exercise and intake of oral contraceptives on endogenous fibrinolytic activity and platelet aggregation behaviour was studied in young healthy women and compared to an age matched group of male volunteers. Physical exercise beyond the anaerobic threshold significantly increased the activity of tissue-plasminogen activator (t-PA) in male and female volunteers from initial values of 1.6 +/- 0.1 and 1.8 +/- 0.2 IU/ml to 5.5 +/- 1.0 and 5.3 +/- 0.9 IU/ml (P less than 0.01), respectively. In women taking low-dose estrogen oral contraceptives t-PA increased from 1.5 +/- 0.2 to 3.8 +/- 0.5 (P less than 0.01). There were no major alterations in plasminogen activator inhibitor - I (PAI-I) plasma activities. Platelet activity during exercise was significantly enhanced in male test persons indicated by a significant decrease in the ED50 values for ADP. In contrast, in women ED50 values were basically unaltered, irrespective of the intake of oral contraceptives.

Adolescent

Effects of ciprostene on restenosis rate during therapeutic transluminal coronary angioplasty.

Ciprostene, a chemically stable prostacyclin analog was studied for its effects on restenosis in patients with coronary artery disease undergoing therapeutic percutaneous transluminal coronary angioplasty (PTCA). In a double-blind, randomized trial 32 patients were randomized to receive either ciprostene or the respective placebo. The infusion started intracoronarily at a rate of 40 ng/kg/min 20 min before introduction of the balloon catheter into the coronary artery. Thereafter infusion was continued intravenously for 36 hours at a rate of 120 ng/kg/min and a tapering off period until 48 hours. The quantitative analyses of the degree of coronary artery stenoses on the angiographic films before PTCA, after PTCA and after 6 month of follow-up was performed in 24 patients available. In patients receiving placebo (n = 12) coronary artery stenoses was 81 +/- 3% before PTCA and was reduced to 34 +/- 3% by angioplasty. At the 6 month follow up angiography stenoses diameter was measured as 63 +/- 8%, being not significantly different from the % stenoses before PTCA. In contrast, coronary artery stenoses in patients receiving ciprostene (n = 12) measured 83 +/- 3% before PTCA, 31 +/- 4% after PTCA and 55 +/- 9% at 6 month, being still significantly different from pre-PTCA value (P less than 0.05). When patients were characterized according to their clinical status, these differences were accounted for by patients with unstable angina receiving ciprostene. Ciprostene seems to reduce restenosis 6 month after coronary angioplasty in patients with unstable angina. The infusion rate of 40 ng/kg/min i.c. followed by 120 ng/kg/min i.v. was tolerated well, although the incidence of catheter associated bleeding was increased.

Adult