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R Vogel

Publications and source records attributed to R Vogel.

243 records · Page 14Linked to original sources
PubMedDate not supplied

Structural requirements and cell-type specificity for ligand activation of peroxisome proliferator-activated receptors.

The mammalian peroxisome proliferator-activated receptor (PPAR) family consists of three different subtypes, PPARalpha, hNUC1/PPARdelta and PPARgamma. Selective agonists have been identified for PPARalpha and PPARgamma but not for hNUC1, and consequently little is known about the genes that are controlled by this receptor. Using ligand-dependent transcription assays in COS-7 cells, we screened a variety of PPAR activating agents to identify a selective activator of hNUC1. We found that the potent peroxisome proliferator, Wy-14643, and the PPARgamma-selective thiazolidinedione, BRL 49653, were poor activators of hNUC1 (EC50s of > 100 microM). Short chain fatty acids (FAs) appeared more selective for PPARalpha than for hNUC1, whereas the very long chain FA, erucic acid (C22:1) was more selective for hNUC1. Using erucic acid as a probe, we conducted a topological similarity search of the Merck Chemical Collection and identified a fatty acid-like compound, L-631,033 4-(2-acetyl-6-hydroxyundecyl) cinnamic acid, that was a selective activator of hNUC1 (EC50 of 2 microM), but was much less selective for PPARalpha or PPARgamma (EC50s of > 100 microM). Structure-function analysis of PPAR activation by L-631,033 structural analogues showed that receptor selectivity depends on the position of the carboxyl group relative to the phenyl ring on the molecule. Transfection experiments in several cell types: an osteoblastic cell line (MB 1.8), a mouse liver cell line (ML-457), rat aortic smooth muscle cells (RSMCs) and COS-7 cells revealed differences in the activation profile of specific ligands. The most notable differences were observed in RSMCs, where transactivation by L-631,033 and Wy-14643, but not by BRL 49653, was markedly reduced, and in MB 1.8 cells, where oleic acid failed to activate PPARs. These findings identify certain structural features in PPAR-activating agents that modulate PPAR activation, and suggest that as with other nuclear receptors, activation is cell-type specific.

Animals↗
PubMedDate not supplied

Percutaneous cardiopulmonary bypass to support angioplasty and valvuloplasty. Technical considerations.

To eliminate problems during percutaneous transluminal coronary angioplasties (PTCAs) or valvuloplasties (PV), percutaneous cardiopulmonary bypass (PCPB) was used in 19 high-risk patients (pts) to perform supported PTCA (12 pts, age 40-68) for low EF and/or a large area of risk (L main), and supported PV (7 pts, age 68-92) for "nonoperative" candidates with severe AS. Our experience promoted a review of the technical aspects of PCPB was needed for a successful outcome in these high-risk patients. All patients were treated with IV amnestics while awake in the catheter laboratory. Early in the experience, 20F arterial and venous cannulas were inserted via a 2 cm cutdown in the right groin; now 17F arterial and 20F venous cannulas are placed via a Seldinger technique using fluoroscopy. Traversement of the iliac vein is enhanced by a roll under the buttocks. If the artery is calcified, a cutdown, vessel loops, and direct repair are employed to assure post-PCPB patency. Total flows of 6L/min are easily achieved with nonreservoir centrifugal pump bypass. If flow or pressures fall, 200 cc of blood or crystalloid rapidly improves venous drainage and flows and unlike during reservoir bypass, alpha agonists are only rarely necessary; CaCl often produces nausea in these patients. PCWP's are brought to 0-5 mm Hg. Due to the 1,500 cc priming volume, on-pump transfusion is often required. Two patients were successfully transported to the OR on PCPB for treatment of catheter failures. With attention to technical details, percutaneous bypass supported PTCA or PV is an important new therapy for high risk patients.

Adult↗
PubMedDate not supplied

Variations on calculating left-ventricular volume with the radionuclide count-based method.

Various methods for the calculation of left-ventricular volume by the count-based method utilizing red-blood-cell labeling with 99mTc and a parallel-hole collimator are evaluated. Attenuation correction, linked to an additional left posterior oblique view, is utilized for all 26 patients. We examine (1) two methods of calculating depth, (2) the use of a pair of attenuation coefficients, (3) the optimization of attenuation coefficients, and (4) the employment of an automated program for expansion of the region of interest. The standard error of the estimate (SEE) from the correlation of the radionuclide volumes with the contrast-angiography volumes, and the root-mean-square difference between the two volume sets at the minimum SEE are computed. It is found that optimizing a single linear attenuation coefficient assumed for attenuation correction best reduces the value of the SEE. The average of the optimum value from the end-diastolic data and that from the end-systolic data is 0.11 cm-1. This value agrees with the mean minus one standard deviation value determined independently from computed tomography scans (0.13-0.02 cm-1). It is also found that expansion of the region of interest beyond the second-derivative edge with an automated program, in order to correctly include more counts, does not lower the SEE as hoped. This result is in contrast to the results of others with different data and a manual method. Possible causes for the difference are given.

Aortic Valve Insufficiency↗
PubMedDate not supplied

The safety and efficacy of topical norfloxacin compared with placebo in the treatment of acute, bacterial conjunctivitis. The Norfloxacin-Placebo Ocular Study Group.

Two hundred and eighty-four patients with acute conjunctivitis were enrolled in a double-masked study comparing norfloxacin ophthalmic solution with placebo. The proportion of patients who were clinically improved after 5 days treatment was 88.1% in the norfloxacin group and 71.6% in the placebo group (p less than 0.01). The proportion of patients who had all organisms eradicated, including the coagulase-negative staphylococci, after two to three days treatment was 52.7% for norfloxacin and 23.9% for placebo (p less than 0.01) and 64.7% and 26.3% (p less than 0.01) respectively when the coagulase-negative staphylococci were not included. Adverse experiences occurred in 4.2% of the patients receiving norfloxacin compared to 7.1% of the placebo patients. None of the adverse experiences was serious.

Acute Disease↗
PubMedDate not supplied

The hemispheric distribution of Torpedo nicotinic receptors expressed in Xenopus oocytes.

The physical and the functional distribution of Torpedo nicotinic-cholinergic receptors expressed in Xenopus oocytes was assayed. Physical hemispheric receptor distribution was tested by binding of 125[I]-bungarotoxin. The density of the expressed nicotinic receptors was equal on both hemispheres (ratio animal/vegetal = 1.1 +/- 0.2). Functional distribution was tested either by whole hemispheric response assay or by monitoring responses from small areas on the two hemispheres. While the first method yielded results that suggested uniform receptor density distribution, the second method indicated two-fold higher responsiveness on the animal hemisphere, when compared with the vegetal hemisphere. Direct comparison on oocytes of the same donors did not reveal significant differences between the two assays. We did see, however, a high variability among the different donors (animal/vegetal activity ratio range 0.5-4.7). Overall, in 35 experiments in 18 donors, the animal/vegetal ratio of hemispheric responsiveness was 1.4. The possible source of this high variability may have been the large excess of bungarotoxin-binding sites over the number of active channels. We have also tested hemispheric responsiveness ratio with different concentrations of acetylcholine. When acetylcholine concentration was below 10 microM, the animal/ vegetal ratio was significantly lower than 1.0. Similar results were obtained with nicotinic receptors expressed after injection of RNA transcribed in vitro from cloned mouse nicotinic receptor subunits. These results imply that hemispheric membrane heterogeneity may affect receptor and/or channel activities to yield polarized channel activity despite nearly homogeneous receptor distribution.

Animals↗
PubMedDate not supplied

[The relation between suicide and psychiatric disease in advanced age].

This report addresses the relation of suicide to mental illness in the elderly. Our investigation of this relation proceeds from the following two points of view: First we asked whether the fact that the elderly are most at risk from suicide is enhanced by their increased psychiatric morbidity. Secondly, sought to determine to what extent suicides of older mentally ill persons are definitely a result of their mental illness. The sample includes 310 suicides of psychiatric inpatients. These were investigated in the course of a multicenter study of six psychiatric State Hospitals in southern West Germany. The method of analysis involved the motives of the suicidal acts. Results demonstrate that age is an autonomous risk factor and not affected by psychiatric morbidity. Psychiatric morbidity of older persons is not sufficient to explain the suicidal act. Moreover, we found that if mental illness played a part, motives reflecting aspects of chronicity predominated motives reflecting psychopathology (i.e., being presecuted, losing one's mind) of the suicidal patients. Results are discussed with special reference to prevention and management of suicide risk factors in the elderly.

Aged↗