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Biomedical subjects

J Meyer

Publications and source records attributed to J Meyer.

At least 343 records · Page 19Linked to original sources

Tissue Doppler echocardiography: a new method of evaluating perfusion-dependent myocardial function during PTCA.

The increasing demand for insight into the relationship between coronary perfusion and myocardial function stimulated the development of tissue Doppler echocardiography. This new technique was applied simultaneously with PTCA of a subtotal LAD lesion (single vessel disease, no collaterals) in a 68-year-old patient suffering from unstable angina pectoris. Prior to the conventional signs of ischaemia a decrease in myocardial tissue velocities and a loss of color-coded heart cycle intervals was observed. A myocardial velocity gradient calculated from the higher subendocardial and lower subepicardial velocity decreased from 3.3 to 1.3. This decrease was prevented by an active autohaemoperfusion device which supplied blood distally to an insufflated balloon (60 ml/min). Thus, contractility and viability might be maintained by preserving myocardial velocity gradients.

Aged↗

Dynamic stress echocardiography for evaluating anti-ischemic drug profiles in post-MI patients.

Exercise ECG is an established method of evaluating the anti-ischemic properties of drugs. However, there are considerable methodologic limitations to this procedure and its use is restricted to patients with exercise-provoked ECG alterations which can be interpreted as ischemia. The principal, earlier onset of wall motion abnormalities according to the ischemic cascade can be detected by stress echocardiography and might be utilized as a pharmacological stress testing modality. Sixteen consecutive patients (15 men, one woman; 53 +/- 9 years old) with angiographically proven coronary artery disease (8 with one-, 5 with two-, and 3 with three-vessel disease) and exercise-induced wall motion abnormalities were examined by dynamic stress echocardiography (50 watt followed by 20-watt increases/min). Anti-ischemic drugs were withdrawn prior to and on day 1; on the following day 2, 0.2 microgram/kg/min nisoldipine was infused intravenously during the test after a 3 micrograms/kg bolus was given. At maximum comparable workload 15/16 patients showed an improved wall motion score on treatment (day 1: 22.9 +/- 4.9 vs day 2: 20.0 +/- 3.9; normal score: 12; one-sided binomial test: p = 0.0003). Eight of 16 patients demonstrated ST-segment deviations on day 1 and day 2. The double product did not differ at any workload stage until the maximum of 130 watt (day 1: 14,101 +/- 3140 vs day 2: 13,365 +/- 2865; n.s.). Dynamic stress echocardiography seems to be a valuable tool in pharmacologic stress testing and in terms of accuracy is supposed to be superior to conventional exercise ECG. Nisoldipine reduces exercise-induced wall motion abnormalities in patients with and without exercise-induced ECG alterations. The data result from a controlled pilot study, and further studies are required to confirm these promising methodological and therapeutic findings.

Adult↗

Age changes in the causes of individual differences in conservatism.

Age-related changes are analyzed in the correlation of 3416 monozygotic and 3780 dizygotic U.S. twin pairs aged between 9 and 75+ years for conservatism scores derived from a 28-item social attitude inventory. The effects of the shared environment are overwhelming in twins aged 20 years or younger. In older twins, genetic effects appear to play a larger role. A more dynamic conception of the interaction between genes and environment in the development of complex human differences is needed.

Adolescent↗

[Spiral CT for the detection of coronary artery calcifications and the prognosis of coronary heart disease--a comparison with fluoroscopy and coronary angiography].

PURPOSE: Evaluation of clinical relevance of coronary calcifications detected by helical CT. Evaluation of congruence with fluoroscopy (FS) and coronary angiography. Comparison with studies reporting on application of ultrafast computed tomography. MATERIALS AND METHODS: 40 patients underwent helical CT (2 mm slice thickness, table-feed 3 mm/s). Coronary angiography and FS were performed in usual technique. Stenosis and calcifications were evaluated semiquantitatively. RESULTS: 28 of 28 stenoses > or = 75% were detected via helical CT by evaluation of calcification (FS: 19). One non-detected solitary stenosis was calculated as 40%. FS did not detect 4 cases with 2-vessel and 3-vessel disease each one case with 1-vessel disease, and one case with a main stem stenosis. Sensitivity of helical CT was 97% (FS: 66%). For the evaluation of stenosis III degree (> or = 75%), sensitivity was 100% (FS: 58%), specificity was 77% (FS: 48%). CONCLUSION: Helical CT is more sensitive for haemodynamically relevant stenoses than FS. Helical CT is suitable as a substantial non-invasive diagnostic procedure in coronary heart disease. In certain cases, e.g. if the patient suffers from additional risks, helical CT should be done prior to coronary angiography. Coronary calcifications found incidentally in symptomatic patients at chest CT warrant further cardiological investigation.

Adult↗

Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations.

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG) domain. They either reduce or abolish the DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense and three frameshift mutations identified, two leave the C-terminal transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or almost completely intact. When tested in cell transfection experiments, the recurrent nonsense mutation Y440X, found in two patients who survived for four and more than 9 years, respectively, exhibits some residual transactivation ability. In contrast, a frameshift mutation extending the protein by 70 residues at codon 507, found in a patient who died shortly after birth, showed no transactivation. This is apparently due to instability of the mutant SOX9 protein as demonstrated by Western blotting. Amino acid substitutions and nonsense mutations are found in patients with and without XY sex reversal, indicating that sex reversal in CD is subject to variable penetrance. Finally, none of 18 female patients with XY gonadal dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP assays, providing evidence that SOX9 mutations do not usually result in XY sex reversal without skeletal malformations.

Child↗

Expression of intercellular adhesion molecule 3 (CDw50) on endothelial cells in cutaneous lymphomas. A comparative study between nodal and cutaneous lymphomas.

Advances in the molecular definition of surface proteins (adhesion molecules) involved in tumor metastasis may help to explain the invasive behavior of malignant tumors, that is, the migration of tumor cells involving reversible adhesive contacts, their release in the circulation, and their extravasation into distant sites. Intercellular adhesion molecule-3 (ICAM-3), the third receptor for the lymphocyte function-associated antigen molecule-1 (LFA-1) was recently characterized. We investigated fresh frozen skin biopsies from 10 patients with mycosis fungoides, four with pleomorphic T-cell lymphoma, six with Sézary syndrome, 10 with primary cutaneous B-cell lymphoma, and 10 with eczematous lesions as controls. The biopsies were compared with lymph node biopsies of five patients with known cutaneous T-cell lymphoma (CTCL), 10 with primary nodal B-cell lymphoma, and 11 with lymph-node specimens showing dermatopathic lymphadenopathy as controls. The specimens were stained with ICAM-3 antibody (Bender Medical Science) using the alkaline phosphatase antialkaline phosphatase method. Using cytomorphologic criteria, neoplastic lymphocytes could be differentiated from smaller reactive cells. Staining intensities were classified semiquantitatively as follows: 4, strong expression in 75 to 100% of the tumor cells; 3, 50 to 75%; 2, 25 to 50%; 1, 5 to 25%; and 0 fewer than 5% of the tumor cells. The endothelial cells in skin biopsies of seven of 30 primary cutaneous lymphomas expressed ICAM-3. In contrast, no expression of ICAM-3 could be demonstrated on endothelial cells in lymph nodes infiltrated with tumor cells of CTCL. Finally, endothelial cells of lymph nodes infiltrated with primary nodal B-cell lymphomas showed expression of ICAM-3 in three of 10 patients. The endothelial cells in the 11 control patients presenting with both eczematous lesions and dermatopathic lymphadenopathy showed no staining for ICAM-3. Every patient who expressed ICAM-3 on endothelial cells showed systemic spread of this disease. The findings suggest that ICAM-3 expression may be induced on endothelial cells in late-stage cutaneous lymphomas, probably by a cytokine-mediated mechanism.

Adult↗

Beta-adrenergic stimulation enhances left ventricular diastolic performance in normal subjects.

To determine the effects of beta-adrenergic stimulation on transmitral Doppler echocardiography flow characteristics of left ventricular diastolic filling, we studied 10 healthy volunteers aged 23-31 years (mean age, 26.6 years) during intravenous infusion of isoprenaline in consecutive steps of 0.1, 0.2, 0.4, 0.75, and 1.5 micrograms/min (each for 15 min). Saline control infusion was given in the same manner in a crossover and blinded protocol. Compared with the infusion of placebo, stepwise increasing doses of isoprenaline caused a dose-related increase in early and late diastolic filling velocities and velocity-time integrals, a lengthening of the acceleration time, and a shortening of the deceleration and filling time. The chosen method proved highly sensitive, as statistically significant changes were detectable at the lowest dose of 0.1 microgram/min for all variables except velocity-time integral of late filling and deceleration time (> or = 0.2 microgram/min). The effects related to dose in a log-linear fashion except for the lengthening of the acceleration time (early ceiling), the increase of peak early filling velocity (increased steepness at higher doses), and the shortening of the filling time. Inclusion of the associated increases in heart rate and systolic blood pressure and the decrease in diastolic blood pressure blunted all treatment contrasts except for the increase of peak early filling velocity. In addition, the hemodynamics with respect to heart rate and loading conditions were not altered at low dosages of drug (< 0.4 microgram/min). Effects of at least the peak early filling velocity must be interpreted as an active adrenergically mediated myocardial relaxation process. These findings have potentially important clinical implications for this noninvasive, readily available, and convenient technique in clinical pharmacology, stress testing, and possibly therapeutic interventions in diastolic dysfunction in humans.

Adrenergic beta-Agonists↗

Occurrence of temperate bacteriophages in different Actinobacillus actinomycetemcomitans serotypes isolated from periodontally healthy individuals.

The occurrence of temperate bacteriophages was studied in 34 isolates of Actinobacillus actinomycetemcomitans derived from 27 periodontally healthy Finnish individuals both by lysis/plaque assays and by DNA hybridizations. In addition the serotype, the ribotype and the arbitrarily primed polymerase chain reaction (AP-PCR) profile were determined for each A. actinomycetemcomitans strain. Fourteen isolates showed hybridization patterns very similar to that of a known lysogen when probed with the genome of the previously characterized temperate phage Aa phi 23. Only 6 of these 14 strains had produced lysis or single plaques on suitable indicator strains. Phage Aa phi 247 derived from one of these lysogens was indistinguishable from Aa phi 23 by electron microscopy, and the genomes showed highly related DNA hybridization patterns. The remaining 20 isolates exhibited hybridization patterns very different from that of Aa phi 23 DNA. Seven of these strains also gave lysis or single plaques, suggesting that 21 of the 34 strains were lysogenic. These data indicate that the prophages per se do not represent a virulence factor exclusively associated with periodontal disease. Presence of an Aa phi 23-related prophage correlated with serotype a and AP-PCR type 1 of the bacterial host. This may indicate that Aa phi 23 and related phages have a limited host range.

Adolescent↗

Presence of bacteriophage Aa phi 23 correlates with the population genetic structure of Actinobacillus actinomycetemcomitans.

Several bacteriophages associated with the oral bacterium Actinobacillus actinomycetemcomitans have been identified. Lysogeny might affect the virulence of this bacterium, which has been implicated in the etiology of juvenile and adult periodontitis. We have determined the presence of bacteriophage Aa phi 23-related DNA sequences among 185 A. actinomycetemcomitans strains belonging to 2 well-characterized collections and have related the findings to the population genetic structure of the collections. 2 cloned Aa phi 23-specific DNA probes were used in Southern blot hybridization experiments to detect homologous sequences in whole-cell DNA of the strains. DNA from 65 (35%) of the 185 strains hybridized to either of the DNA probes. The majority (74%) of the hybridizing strains showed an identical hybridization pattern, indicating presence of phage Aa phi 23. Whole-cell DNA from the remaining hybridizing strains hybridized to the probes with different patterns, indicating that DNA sequences related to but different from phage Aa phi 23 occur in these strains. The majority (81%) of the strains which harbored phage Aa phi 23 were of serotype a, whereas serotype d strains appeared to be resistant to infection with this phage. There was a clear correlation between hybridization patterns and genetic subdivisions based on our previous population genetic analyses of A. actinomycetemcomitans. However, there was no significant correlation between occurrence of Aa phi 23 among A. actinomycetemcomitans strains and the periodontal status of the patients from whom the isolates were obtained, suggesting that this bacteriophage does not significantly influence the virulence of A. actinomycetemcomitans.

Abscess↗

The potent enhancer activity of the polycythemic strain of spleen focus-forming virus in hematopoietic cells is governed by a binding site for Sp1 in the upstream control region and by a unique enhancer core motif, creating an exclusive target for PEBP/CBF.

The polycythemic strain of the spleen focus-forming virus (SFFVp) contains the most potent murine retroviral enhancer configuration known so far for gene expression in myeloerythroid hematopoietic cells. In the present study, we mapped two crucial elements responsible for the high activity of the SFFVp enhancer to an altered upstream control region (UCR) containing a GC-rich motif (5'-GGGCGGG-3') and to a unique enhancer core (5'-TGCGGTC-3'). Acquisition of these motifs accounts for half of the activity of the complete retroviral enhancer in hematopoietic cells, irrespective of the developmental stage or lineage. Furthermore, the UCR motif contains the major determinant for the enhancer activity of SFFVp in embryonic stem (ES) cells. Using electrophoretic mobility shift assays, we show that the UCR of SFFVp, but not of Friend murine leukemia virus, is targeted by the ubiquitous transcriptional activator, Sp1. The core motif of SFFVp creates a specific and high-affinity target for polyomavirus enhancer binding protein/core binding factor (PEBP/CBF) and excludes access of CAAT/enhancer binding protein. Cotransfection experiments with ES cells imply that PEBP/CBF cooperates with the neighboring element, LVb (the only conserved Ets consensus in the SFFVp enhancer), and that the Sp1 motif in the UCR stimulates transactivation through the Ets-PEBP interaction. Putative secondary structures of the retroviral enhancers are proposed based on these data.

Animals↗

The human immunodeficiency virus transactivator Tat interacts with the RNA polymerase II holoenzyme.

The human immunodeficiency virus (HIV) encodes a transcriptional transactivator (Tat), which binds to an RNA hairpin called the transactivation response element (TAR) that is located downstream of the site of initiation of viral transcription. Tat stimulates the production of full-length viral transcripts by RNA polymerase II (pol II). In this study, we demonstrate that Tat coimmunoprecipitates with the pol II holoenzyme in cells and that it binds to the purified holoenzyme in vitro. Furthermore, Tat affinity chromatography purifies a holoenzyme from HeLa nuclear extracts which, upon addition of TBP and TFIIB, supports Tat transactivation in vitro, indicating that it contains all the cellular proteins required for the function of Tat. By demonstrating that Tat interacts with the holoenzyme in the absence of TAR, our data suggest a single-step assembly of Tat and the transcription complex on the long terminal repeat of HIV.

Animals↗

Increased serum NG-hydroxy-L-arginine in patients with rheumatoid arthritis and systemic lupus erythematosus as an index of an increased nitric oxide synthase activity.

OBJECTIVES: To determine the feasibility of monitoring the serum concentration of NG-hydroxy-L-arginine (L-NHA) as an index of an increased nitric oxide (NO) synthase activity in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) compared with nitrate (NO3-), the major circulating metabolite of NO whose concentration is influenced by dietary intake. METHODS: The serum concentrations of L-NHA, L-arginine (L-Arg), and NO3- were determined in 33 patients with RA, 25 patients with SLE and, 29 healthy subjects. RESULTS: Serum L-NHA was significantly increased in RA patients with high disease activity (287% of control, p < 0.01), but not with low disease activity (115%), as well as in patients with SLE (173%, p < 0.01). In contrast, serum NO3- did not differ significantly between either group of patients and the respective control group. CONCLUSION: NO synthase activity or expression, or both, is upregulated in RA patients with high disease activity and in patients with SLE. Serum L-NHA seems to be a more specific and reliable index of an increased activity of this enzyme in patients with acute or chronic inflammatory diseases than NO3-.

Acute Disease↗

Intravascular ultrasound in patients with acute pulmonary embolism after treatment with intravenous urokinase and high-dose heparin.

OBJECTIVE: To compare the diagnostic value of intravascular ultrasound (IVUS) with angiography in patients with pulmonary embolism. DESIGN: Open, prospective clinical study. SETTING: Two university hospitals. PATIENTS: Angiography and IVUS were used in 11 patients (5 men) (mean (SD) age 50 (18) years) with acute pulmonary embolism. INTERVENTIONS: At a mean (SD) of 6 (4) hours after thrombolytic therapy with urokinase and full-dose heparin, all patients underwent pulmonary artery angiography. Then 3.5 F mechanical, 20 or 30 MHz IVUS catheters were advanced into the pulmonary circulation. MAIN OUTCOME MEASURES: The pulmonary circulation was studied by both methods to detect the presence of thrombus, and a modified Miller score (assessing perfusion defects only and not velocity of flow) was used to quantify the angiographic images. RESULTS: The modified Miller score was mean (SD) 7.4 (2.3) points. 168 pulmonary artery segments (diameter range 2-14 mm) were studied by angiography and IVUS. On angiography, seven segments showed complete obstruction and 49 partial obstruction; 112 were normal. Two distinct types of thrombus formation were found by IVUS. Type A thrombus only partly adhered to the wall but otherwise was mobile and type B predominantly adhered to the wall. IVUS confirmed all seven angiographically complete obstructions but missed three (6%) of the 49 partial occlusions. Forty (87%) of the remaining 46 segments had type A thrombus and six (13%) type B. IVUS indicated a thrombus in 38 (34%) of the 112 angiographically normal segments; 20 (53%) showed a type A pattern and 18 (47%) a type B pattern (P < 0.001). CONCLUSION: IVUS was more sensitive than angiography in detecting thrombus but the clinical impact of this finding is not clear as yet.

Acute Disease↗

Expression, function, and regulation of E-type prostaglandin receptors (EP3) in the nonischemic and ischemic pig heart.

The action of prostacyclin, prostaglandin E1 (PGE1), and their mimetics on myocardial function includes changes in contractility, electrophysiological properties, and protection from injury caused by transient myocardial ischemia. This study was undertaken to investigate the basic properties of myocardial E-type prostaglandin (EP) receptors. Ligand binding studies using an enriched preparation of sarcolemmal membranes prepared from pig hearts revealed a single class of binding sites for [3H]PGE1, with a Kd of 3.7 nmol/L and a Bmax of 92 fmol/mg protein. Competition experiments indicated highest affinity for EPs, suggesting an EP receptor. In addition, the EP receptor subtype-selective agonists sulprostone (EP1 and EP3) and M&B 28.767 (EP3) were active, suggesting the presence of an EP3 receptor subtype. PGE1 stimulated sarcolemmal GTPase and inhibited sarcolemmal adenylyl cyclase activity, indicating EP3 receptor coupling to an inhibitory G protein (Gi). Additional in vivo experiments showed that intracoronary infusion of PGE1 (1 nmol/min) decreased isoprenaline-stimulated left ventricular contractile activity without altering systemic vascular resistance. This inhibition of beta-adrenergic effects is compatible with the known myocardial anti-ischemic action of prostaglandins. Further experiments examined EP3 receptor density and G-protein coupling in sarcolemma from ischemic and reperfused ischemic myocardium. In anesthetized open-chest minipigs, occlusion of the left anterior descending coronary artery for 60 minutes increased EP3 receptor density by 50%, whereas receptor affinity was unchanged. This upregulation was prevented by pretreatment with colchicine (2 mg/kg i.v.), indicating microtubule-dependent receptor externalization. Northern hybridization showed comparable EP3 receptor mRNA expression in control and ischemic myocardium. The increase of receptor protein was reversed during 60 minutes of reperfusion. G-protein coupling proved to be intact in ischemic and reperfused ischemic myocardial tissue, as shown by preserved GTP-gamma-S-induced decrease of [3H]PGE1 binding. These data demonstrate for the first time that myocardial receptors for PGE1 belong to the EP3 subtype. The properties of this receptor include inhibition of adenylyl cyclase and upregulation during regional myocardial ischemia, suggesting an involvement in the anti-ischemic activity of E- and I-type prostaglandins.

Alprostadil↗

Demonstration of a combined filter to improve the field uniformity of a 90 kV superficial X-ray therapy machine for different treatment field sizes.

The field uniformity of a superficial X-ray machine operating at 90 kV, 10 mA and filtered with a 1.1 mm aluminium beam hardening filter was investigated at a depth of 1 cm below the surface. Uniformity measurements were carried out using films and a densitometer to detect the relative absorbed dose across the field. Film dosimetry was assessed by comparison with ionization chamber dosimetry in a water tank. The original flat hardening aluminium filter was replaced by a combined, profiled filter to improve the uniformity across field sizes 20 cm, 5 cm and 2 cm diameter as well as hardening the beam. Flatness of the beam profile was improved for the 20 cm field size from +/-7.5% to +/-1.3% across the anode/cathode direction and from +/-7.9% to +/-4.7% in the anode/cathode direction. For the 5 cm field size the improvement was from +/-4% to +/-3% and from +/-5.3% to +/-3.6% and for 2 cm field size from +/-3.4% to +/-2.8% and from 10.5% to +/-9.7% in the same directions, respectively. Beam quality measurements were made and the original half-value-layer was reduced from 2.21 +/- 0.09 mm to 2.07 +/- 0.09 mm. The project demonstrated that it was possible to build a filter capable of flattening the beam profile for different sized applicators without significantly changing the penetrating ability of the beam.

Film Dosimetry↗