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J Meyer

Publications and source records attributed to J Meyer.

At least 379 records · Page 21Linked to original sources

Activation of Gal4p by galactose-dependent interaction of galactokinase and Gal80p.

Yeast galactokinase (Gal1p) is an enzyme and a regulator of transcription. In addition to phosphorylating galactose, Gal1p activates Gal4p, the activator of GAL genes, but the mechanism of this regulation has been unclear. Here, biochemical and genetic evidence is presented to show that Gal1p activates Gal4p by direct interaction with the Gal4p inhibitor Gal80p. Interaction requires galactose, adenosine triphosphate, and the regulatory function of Gal1p. These data indicate that Gal1p-Gal80p complex formation results in the inactivation of Gal80p, thereby transmitting the galactose signal to Gal4p.

Amino Acid Sequence↗

[Long term course over 10 years after balloon dilatation in stable and unstable angina pectoris].

OBJECTIVE: To assess the cardiac status of patients ten years after percutaneous transluminal coronary artery angioplasty (PTCA). PATIENTS AND METHODS: Data of 534 patients (436 men, 98 women; mean age 53.2 +/- 8 years) in whom a PTCA had been performed between 1983 and 1986 were analysed, based on a questionnaire answered 121 +/- 11 months after the initial procedure. At the time of PTCA 184 patients (35%) had unstable angina, 350 (65%) stable angina. RESULTS: 116 patients (63%) with unstable angina and 164 (47%) with stable angina had at least one cardiac event after the initial PTCA (repeat PTCA, bypass operation, myocardial infarction, death). None of these events occurred in 68 patients (37%) with unstable or in 186 (53%) with stable angina (P < 0.001). After 10 years 196 of the 302 surviving patients with stable angina (65%) and 104 of the 153 surviving patients with unstable angina (68%) were symptom-free. CONCLUSIONS: Ten-year follow-up after PTCA has shown that cardiac events are significantly more frequent in patients who had had unstable angina than in those with stable angina. This difference already develops in the first year post-PTCA, with no increase later. Symptoms are lastingly improved after 10 years in both groups of patients.

Angina Pectoris↗

Molecular mechanism of pyruvate-ferredoxin oxidoreductases based on data obtained with the Clostridium pasteurianum enzyme.

Pyruvate-ferredoxin oxidoreductase oxidises pyruvate in many fermentative microorganisms. The enzyme from Clostridium pasteurianum is an air-sensitive homodimer of 2x120000 daltons, for which pyruvate is the best substrate found among several alpha-ketoacids. Each subunit contains eight iron atoms in two [4Fe-4S] clusters. Two distinct EPR signals, possibly associated with two ligand environments, arise from one of these clusters. Binding of pyruvate does not generate a radical. The results reported suggest a scheme for the electron flow in pyruvate ferredoxin oxidoreductases according to which the detailed reaction mechanism depends on the number (even or odd) of [4Fe-4S] clusters present in a given enzyme.

Catalysis↗

Development of ST-segment elevation and Q- and R- wave changes in acute myocardial infarction and the influence of thrombolytic therapy.

Sequential electrocardiograms for admission to 36 hours in 358 patient s with acute myocardial infarction (AMI) from the Pro-urokinase In Myocardial Infarction trial were assessed. The electrocardiogram was also examined at discharge in 69 of 358 patients. Patients underwent acute angiography, after which angioplasty was performed in most patients with impaired flow. The sum of the ST-segment deviation and Q- and R- wave voltages, and the QRS score were calculated and used for further evaluation. Development of Q waves, lost of R waves, and QRS score were completed within the first 9 hours after onset of AMI and remained stable thereafter. Reperfused patients had earlier stabilization and less severe electrocardiographic (ECG) abnormalities than nonreperfused patients. ST-segment elevation had already stabilized after 5 hours, was unchanged at 36 hours, and had significantly decreased at discharge. No significant ECG and clinical outcome differences were found between the Thrombolysis In Myocardial Infarction trial (TIMI) 2 and TIMI 3 patients. A 23.3% gain in ECG-estimated infarct size was found in the reperfusion group compared with a 12.0% gain in the nonreperfused group (p = 0.08). In summary, as early as 9 hours after onset of AMI, QRS changes were already complete. Thereafter, QRS morphology was stable. Thus, a QRS-based estimation of infarct size can be made as early as 9 hours after AMI. A similar ECG outcome for patients with TIMI 2 and 3 flow was found, which was significantly different from patients with TIMI 0 to 1 flow.

Aged↗

Heterogeneity among juvenile antisocial behaviours: findings from the Virginia Twin Study of Adolescent Behavioural Development.

The examination of heterogeneity in antisocial behaviour was accomplished by applying latent class analytic methods to multivariate categorical data on 389 same-sex male twins, aged 11 to 16 from the Virginia Twin Study of Adolescent Behavioural Development (VTSABD). The data included multiple measures of oppositional and conduct disorder, attention deficit disorder, hyperactivity, impulsivity, reading disability and anxiety from mother, teacher, and child report from both questionnaire and interview (child and adult psychiatric assessment; CAPA). A latent four-class model provided a good fit to the data and yielded four phenotypically and aetiologically distinct latent classes: (1) a non-symptomatic class influenced by both additive genetic and shared environmental factors; (2) a hyperactivity-conduct disturbance class accounted for by both additive and non-additive genetic effects; (3) a 'pure' conduct disturbance class with a very strong shared environmental component; and (4) a multisymptomatic class explained entirely by the additive effect of the genes. Further characterization of these four latent classes by age of the child and parental psychiatric history is also shown.

Adolescent↗

Morphine-6-O-beta-D-glucuronide but not morphine-3-O-beta-D-glucuronide binds to mu-, delta- and kappa- specific opioid binding sites in cerebral membranes.

We investigated the nature of interaction of morphine-3-O-beta-D-glucuronide (M3G) and morphine-6-O-beta-D-glucuronide (M6G) with opioid binding sites at the mu-, delta- and kappa-opioid receptors (mu-OR, delta-OR and kappa-OR) in cerebral membranes. Saturation binding experiments revealed a competitive interaction of M6G with all three opioid receptors. Inhibition binding experiments at the mu-OR employing combinations of morphine and M6G resulted in a rightward shift of the IC50 for morphine proportional to the M6G concentration, thus strengthening the finding of competitive interaction of M6G at the mu-opioid binding site. Data in absence and presence of M6G were included in a three-dimensional model. Compared to a model with one binding site a model with two binding sites significantly improved the fits. This might indicate that different mu-OR subtypes are involved. Hydrolysis of M6G to morphine was investigated and did not occur. Therefore the effects of M6G on binding to the mu-OR were due to M6G and not due to morphine. In contrast, M3G at the three opioid receptors was found to inhibit binding being about 300 times weaker than morphine. This effect was well explained by the amount of contaminating morphine (about 0.3%) identified by HPLC. We conclude that M6G binds to mu-, delta- and kappa-OR in a competitive manner. Some of our results on the mu-OR suggest two binding sites for agonists at the mu-OR and that M6G binds to both sites. Our results suggest that the high potency of M6G as an analgesic is mediated through opioid receptors. In contrast, M3G does not interact with the mu-, delta- or kappa-OR. We therefore doubt that any effect of M3G is mediated via opioid receptors.

Animals↗

Importance of calibration for diameter and area determination by intravascular ultrasound.

BACKGROUND: Intravascular ultrasound (IVUS) permits quantitative assessment of the lumen diameter and area of coronary arteries. The experimental study was performed to evaluate the accuracy of diameter and area measurements. METHODS AND RESULTS: Lumen quantitation (lumen diameter D and cross-sectional area A) in lucite tubes (lumen diameter 2.5 to 5.7 mm, Plexiglas) was performed using a mechanical IVUS system (HP console, 3.5 F catheter, Boston Scientific, 30 MHz). The influence of fluid type (blood, water and saline solution), fluid temperature (20 degrees C/37 degrees C), catheter to catheter variation, gain setting and ultrasound frequency (12, 20 and 30 MHz) was determined. In blood at 20 degrees C there was a constant deviation of the measured diameter from the true luminal diameter of -0.29 +/- -0.04 mm (p < 0.06). In water and saline solution at 20 degrees C the mean deviation from true diameter was -0.21 +/- -0.06 mm (p < 0.06). At 37 degrees C, the deviation in blood was greater than at 20 degrees (-0.34 +/- -0.02 mm) which is > 10% in a 3 mm tube (p < 0.06). Three of the ten catheters tested in water at 20 degrees C underestimated true diameter by more than -0.3 mm. The deviation from true diameter (5 mm tube) with varying gain settings was -0.14 mm to -0.23 mm compared to -0.19 mm at standard settings (p > 0.288). At 12 MHz diameter measured was over-estimated. The error in absolute area estimation increased with increasing diameter tested in blood at 37 degrees C (-1.21 to -2.72 mm2), whereas the relative error ([Measured Area-True Area]/True Area x 100 [%]) was more striking at smaller diameters (up to -25% in the 2.5 mm tube). CONCLUSION: Luminal diameters and areas are underestimated by this particular IVUS system. When IVUS imaging and measurements are made during coronary interventions this error should be taken into account with regard to appropriate sizing of the device and the assessment of the postprocedure result. Because systematic errors might also occur in other IVUS system (not tested in this study), it is advisable to ensure that each system is validated prior to clinical use, especially when exact measurements are required.

Calibration↗

Quantification of mitral valve stenosis by three-dimensional transesophageal echocardiography.

The aim of this study was the evaluation of the diagnostic potentials of transesophageal 3D- echocardiography in the determination of mitral valve stenosis. 54 patients were investigated by transthoracic and multiplane transesophageal echocardiography. In 41 patients cardiac catheterization was performed. 3D- echocardiographic data acquisition was performed by automatic transducer rotation at 2 degree increments over a span of 180 degrees. The transesophageal probe was linked to an ultrasound unit and to a 3D- workstation capable of ECG- and respiration gated data acquisition, postprocessing and 2D/3D image reconstruction. The mitral valve was visualized in sequential cross-sectional planes out of the 3D data set. The spatial position of the planes was indicated in a reference image. In the cross-sectional plane with the narrowest part of the leaflets the orifice area was measured by planimetry. For topographic information a 3D view down from the top of the left atrium was reconstructed. Measurements were compared to conventional transthoracic planimetry, to Doppler-echocardiographic pressure half time and to invasive data. The mean difference to transthoracic planimetry, pressure half time and to invasive measurements were 0.3 +/- 0.1 cm2, 0.2 +/- 0.1 cm2 and 0.1 +/- 0.1 cm2, respectively. Remarkable differences between the 3D- echocardiographic and the 2D- or Doppler- echocardiographic methods were observed in patients with severe calcification or aortic regurgitation. In 22% of the patients the 3D data set was not of diagnostic quality. New diagnostic information from a 3D view of the mitral valve could be obtained in 69% of the patients. Thus, although image quality is limited, 3D- echocardiography provides new topographic information in mitral valve stenosis. It allows the use of a new quantitative method, by which image plane positioning errors and flow-dependent calculation is avoided.

Adult↗

Intravascular ultrasound detected classification of coronary lesions as a predictor of dissections after balloon angioplasty.

Dissection after balloon angioplasty of coronary arteries may give rise to an unfavourable early outcome. Compared with coronary angiography, intravascular ultrasound (IVUS) allows more detailed characterisation of dissections. We investigated the incidence and type of dissections after balloon angioplasty in calcified coronary lesions. IVUS was performed in 43 patients with 48 lesions before and after percutaneous balloon angioplasty. Significant calcification was defined as an arc of more than 90 degrees with typical acoustic shadowing. Dissections were classified as type A when the media was not involved by the dissection and as type B when media involvement had occurred. In the group with significant calcification dissection was observed in 79% of the cases vs 38% in the control group (p < 0.03). Type B dissection was present in 71% of the dissections in the calcified lesions vs. 15% in the control group (p < 0.02). The balloon diameter and the ratio of balloon area to vessel area was not different in both groups but the required pressure for the first complete balloon inflation was significantly greater in the group with calcified lesions (9.46 +/- 3.6 atm vs. 6.65 +/- 2.6 atm; p < 0.001). Thus balloon angioplasty in calcified coronary lesions is more likely to lead to dissection with frequency involve the media.

Adult↗

Translocation breakpoints in three patients with campomelic dysplasia and autosomal sex reversal map more than 130 kb from SOX9.

Campomelic dysplasia (CMPD1) and autosomal XY sex reversal (SRA1) are caused by mutations in the SRY-related gene SOX9 on 17q. Unexpectedly, the 17q breakpoints in four CMPD1 translocation cases previously analyzed by us and others map 50 kb or more from SOX9. Here, we present clinical, cytogenetic, and molecular data from a new CMPD1/SRA1 patient with t(6;17)(q14;q24). Fluorescence in situ hybridization has shown that the 17q breakpoint in this case maps to the same region as the breakpoints in the other translocation cases, at least 130 kb from SOX9. Likewise, the breakpoints in two of the previously described cases also map more than 130 kb and, as shown by pulsed field gel electrophoresis analysis, at most 400 kb or 690 kb from SOX9. By using a SOX9 coding sequence polymorphism, expression of both SOX9 alleles has been demonstrated by the reverse transcriptase polymerase chain reaction in lymphoblastoid cells from one of the translocation cases.

Alleles↗

[Limitations of inhaled vasodilators].

Treatment of pulmonary hypertension is an important issue in intensive care. One therapeutic regimen involves the intravenous administration of prostacyclin (PGI2). This, however, is accompanied by diminished hypoxic pulmonary vasoconstriction, reduced arterial oxygenation, and systemic vasodilation. Thus, its clinical usefulness is limited. However, the inhalation of vasodilators such as nitric oxide (NO) or nebulized PGI2 causes a selective pulmonary vasodilation in ventilated alveoli and improved gas exchange, without any systemic vasodilation. It has therefore gained importance for the treatment of pulmonary failure associated with high shunt fractions. However, the inhalation of vasodilators may have adverse effects: in the case of NO, toxic side effects are predominant (MetHb, NOx), whereas in the case of PGI2, technical problems in terms of dosing and administration safety are of major interest. Furthermore, some patients do not respond to the treatment. In some individuals a reduction in pulmonary hypertension can be seen, while others lack even pulmonary vasodilation. The exact pathophysiological mechanisms remain to be investigated.

Administration, Inhalation↗

Mothers' lay models of the causes and treatment of fever.

Mothers' intuitive models concerning the causes of fever in their children and their beliefs about the effects of different treatments were compared to modern, folk and ancient models of the subject. A questionnaire was devised, presenting statements that were generated from the responses in a preliminary study, and from ancient, folk and modern views about fever. This questionnaire was answered by 147 mothers whose youngest child was up to eight years old. The sample consisted of four groups, who differed in their educational background: less than 10 years, 10-12 years and more than 12 years of schooling, and a group of professional nurses. Results reveal a complex picture. Unlike in physics, naive understanding does not duplicate ancient models. With increasing education, the views held by the ancient and contemporary folk beliefs are rejected. Many results of modern science are known throughout the population, and this is true both for practical recommendations and for their rationale. Even so, the medical model is only partly accepted, and is assimilated in a somewhat distorted form.

Adult↗

Influence of vessel dilatation on restenosis after successful percutaneous transluminal coronary angioplasty.

The aim of this study was to evaluate the influence of vessel dilation on restenosis after successful percutaneous transluminal coronary angioplasty (PTCA) on the basis of quantitative angiographic analysis. To have the best comparison possible, we restrospectively studied a homogenous series of patients from the early 1980s treated according to a standardized PTCA procedure. The study group consisted of 86 patients with stable angina pectoris and single-vessel disease, all of whom underwent successful PTCA for a short concentric lesion in proximal vessel parts. The overall restenosis rate was 27%. Angiographically measured balloon size remained below specifications. The size of the inflated balloon at the site of minimal lumen diameter averaged 2.6 +/- 0.5 mm, and nominal balloon size was 3.3 +/- 0.4 mm (p < 0.001). In 22 patients with an oversized balloon (mean balloon/artery ratio 1.1 +/- 0.16) the restenosis rate was 5% compared with 34% in the corresponding group (p = 0.02). Minimal lumen diameters that were similar after the procedure (2.4 +/- 0.3 vs 2.3 +/- 0.4, NS) were 2.3 +/- 0.4 mm and 1.8 +/- 0.7 mm, respectively, at follow-up (p = 0.002). Multivariate analysis revealed balloon/vessel size ratio (p < 0.001), postprocedure diameter stenosis (p = 0.02), and percentage diameter increase produced by PTCA (p = 0.04) as independent correlates of the late outcome. Postangioplasty minimal lumen diameter was not related to restenosis. The strongest and most significant predictor of late PTCA outcome both by univariate and multivariate analysis was balloon/vessel size ratio, especially when balloon expansion at the site of minimal lumen diameter was regarded. In patients with continued success at follow-up, the ratio was 0.81 +/- 0.15 compared with 0.60 +/- 0.11 in patients with restenosis (p < 0.001). Our results suggest that the late angiographic outcome of PTCA is strongly influenced by procedural factors. It appears that in a selected group of patients, an increased balloon/artery ratio, supposedly associated with increased vessel wall stretch, favorably affects the restenosis process.

Aged↗