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Biomedical subjects

R Wagner

Publications and source records attributed to R Wagner.

At least 415 records · Page 23Linked to original sources

[Sonographic volumetry of the thyroid gland in the control o thyroxin and iodide treatment of non-toxic goiter].

In a prospective study 39 patients with diffuse euthyroid goitre were treated for one year with 100 micrograms levothyroxine (n = 19) or 500 micrograms iodide (n = 20). Efficacy of treatment was assessed by sonographic thyroid volumetry . In both forms of treatment maximum volume decrease was already seen within the first six months. After treatment for one year the mean decrease of thyroid volumes was 27.5% in the thyroxine group and 22% in the iodide group. This difference was statistically not significant. There was no difference in the extent of goitre size reduction within the thyroxine group among patients with complete TSH suppression and with still positive TRH test. Significant increases of T4 and of fT4 values within the normal range were observed already after one month with thyroxine treatment and only after 3 months with iodide treatment. There were no changes of the T3 values. In one female patient iodine-induced hyperthyroidism occurred. However, there were no further side effects in both treatment groups. This randomised study documents for the first time that both 500 micrograms of iodide and 100 micrograms of levothyroxine have a comparable efficacy for reduction of goitres.

Adolescent↗

[Nail dyschromia as the leading symptom in chronic mercury poisoning caused by a cosmetic bleaching preparation].

Prolonged use of a cosmetic cream containing mercury induced a greenish black nail discoloration in a 56-years-old female patient. Electron microscopy as well as energy-dispersive X-ray analysis identified mercury in the cells of the nail plate. The patient showed mild symptoms of a chronic mercury intoxication with high levels of mercury in serum and urine. Treatment with 2,3-dimercaptopropane-1-sulfonate was effective and well tolerated.

Chronic Disease↗

Regional cerebral glucose metabolism in man during wakefulness, sleep, and dreaming.

Regional cerebral glucose metabolism was measured by positron emission tomography in 4 healthy male volunteers, both during wakefulness and sleep, using the 2-deoxy-D-[2-18F]glucose method. While 3 of the subjects did not report dreaming and, during sleep stages I-IV of variable duration, exhibited a non-selective decrease in metabolic rates averaging 12.6 +/- 4.73% (mean +/- S.D.) for the entire brain, the fourth volunteer who experienced an extended nightmare during his sleep examination showed a generalized increase in cerebral glucose utilization ranging from 2.1% in lentiform nucleus to 30.0% in the superior frontal cortex, with a weighted whole brain average of 16.4%. These findings suggest that energy metabolism in the human brain is generally depressed during slow-wave sleep as opposed to a--possibly differential--activation during dreaming.

Adult↗

Quaternary structure of chloroplast F1-ATPase in solution. Conformational changes in spatial arrangement of subunits upon activation.

The hydrodynamic properties of isolated ATPases were studied via their rotational diffusion in buffer solution. Chloroplast F1-ATPase (CF1) and Escherichia coli F1-ATPase (EF1) were covalently labeled with eosinisothiocyanate and then investigated by polarized laser spectroscopy. The rotational correlation time in aqueous buffer of latent (five-subunit) CF1 was 390 ns. Four-subunit (delta-deficient) CF1 showed the same correlation time, however, for three-subunit (delta, epsilon-deficient) CF1 the rotational correlation time was more than eight times larger (3200 ns). The rotational correlation time of activated CF1 was three times larger than the one of latent CF1. These large changes in the rotational correlation times are directly related to changes in the quaternary structure of CF1 upon activation. EF1 was found to behave essentially as activated CF1. Based on the observed rotational correlation times we concluded that the mass distributions of latent CF1 and of delta-deficient CF1 resemble a dimeric arrangement. The structure of delta, epsilon-deficient CF1 more likely resembles a hexagon, the mass centers of the six main subunits lie in one plane. The structure of the activated forms of CF1 can be described best as an intermediate between the dimeric arrangement of latent CF1 and an octahedron. The large changes in the quaternary structure of isolated CF1 are reversed when the activation of the enzyme is reversed.

Chemical Phenomena↗

Are the toxicities of pentobarbital and ethanol mediated by the GABA-benzodiazepine receptor-chloride ionophore complex?

Both barbiturates and ethanol have been reported to interact with the GABA-benzodiazepine receptor-chloride ionophore 'supramolecular complex'. These observations raise the possibility that some of the pharmacologic actions of barbiturates and ethanol may be mediated through this complex. In this study we have administered a series of drugs which bind to various components of the complex in an attempt to antagonize the lethality of sodium pentobarbital, and ethanol-induced loss of righting reflex in mice. It was found that isopropylbicyclophosphate (IPPO), a cage convulsant which binds at or near the chloride ionophore, greatly reduces the overall mortality (and increases latency to death) of animals pretreated with a lethal dose of pentobarbital. Picrotoxin also decreases pentobarbital lethality, but only at doses which were usually lethal when given alone. Picrotoxin shortened, rather than increased, latency to death. Strychnine did not prevent pentobarbital lethality, suggesting that the IPPO effect is not shared by convulsants in general. IPPO did not prevent ketamine-induced deaths, which supports the notion that the protective actions of IPPO are specific for depressant drugs which act at the chloride ionophore. IPPO also significantly reduced the duration of loss of righting reflex induced by ethanol. These observations suggest that the use of compounds which have a high affinity for the chloride ionophore in vitro might be fruitful in developing a clinical treatment for barbiturate or ethanol toxicity.

Animals↗

Effects of the ribosomal subunit association on the chemical modification of the 16S and 23S RNAs from Escherichia coli.

70S ribosomes and 30S and 50S ribosomal subunits from Escherichia coli were modified under non-denaturing conditions with the chemical reagent dimethylsulfate. The ribosomal 23S and 16S RNAs were isolated after the reaction and the last 200 nucleotides from the 3' ends were analyzed for differences in the chemical modification. A number of accessibility changes could be detected for 23S and 16S RNA when 70S ribosomes as opposed to the isolated subunits were modified. In addition to a number of sites which were protected from modification several guanosines showed enhanced reactivities, indicating conformational changes in the ribosomal RNA structures when 30S and 50S subunits associate to a 70S particle. Most of the accessibility changes can be localized in double-helical regions within the secondary structures of the two RNAs. The results confirm the importance of the ribosomal RNAs for ribosomal functions and help to define the RNA domains which constitute the subunit interface of E. coli ribosomes.

Binding Sites↗

Rapid procedure for the preparation of ferredoxin-NADP+ oxidoreductase in molecularly pure form at 36 kDa.

Ferredoxin-NADP+ oxidoreductase (FNR, EC 1.18.1.2) was purified to molecular homogeneous form as judged by regular and sodium dodecyl sulfate (SDS)-electrophoresis using EDTA extraction of spinach thylakoids, followed by anion exchange on DEAE-cellulose, Procion Red HE 3B dye-ligand chromatography, and hydroxyapatite chromatography. By this procedure, within 1 week approx 7.5 mg of pure FNR, starting from 1 kg of spinach leaves, could be routinely obtained. By comparison with commercially available FNR and with aged preparations two different molecular forms of the enzyme were observed in SDS-electrophoresis. FNR prepared according to the described procedure revealed an apparent molecular mass of 36,000 Da, whereas all other tested preparations showed molecular masses of 3000 Da smaller. Migration in regular gel electrophoresis was the same for all preparations and zymogram stain indicated similar diaphorase activity of both the smaller and the larger forms.

Chromatography↗

Separation and characterisation of light scattering transients from rod outer segments of vertebrate photoreceptors: design and performance of a Multi Angle Flash Photolysis Apparatus (MAFPA).

A device was built for the simple computer-controlled routine determination of the angular dependence of light scattering transients obtained from biological material. It was called Multi Angle Flash Photolysis Apparatus (MAFPA). The MAFPA allows the simultaneous registration of rapid, light-induced light scattering transients at eight scattering angles between 0 degree and 28 degrees. In typical applications changes in scattered light intensity as small as delta I/I = 4 X 10(-5) can be resolved at scattering angles less than 24 degrees, while at 28 degrees the resolution drops to delta I/I = 2 X 10(-4). The time resolution is 32 microseconds. The MAFPA was designed for high accuracy, ease of use and ruggedness. It is made from relatively inexpensive parts and can be copied fairly easily by a good machine/electronics shop. In this communication we describe the design of the MAFPA and how it was used for the characterisation of four structurally distinct light-induced light scattering signals from photoreceptor rod outer segments. These signals are known as P (or binding) signal, G- (or dissociation) signal, N (or rhodopsin) signal and as the ATP-dependent signal AL. The signals have been separated by means of their different angular dependence, their different saturation behavior and nucleotide requirement. A great number of detailed studies will have to be carried out before one can fully understand the physical and biochemical origin of these signals. At this point, however, it can be stated that the so-called 'dissociation signal', showing an angular dependence indicative of a change in refractive index or scattering mass, is not merely an inversion of the preceding 'binding signal', the latter clearly reflecting a gross structural change, i.e. a shrinkage of the disks. Moreover, there are conditions where P signals are observed to persist even after the completion of the subsequent dissociation signals. The two remaining signals N and AL show a pronounced angular dependence which is not easily interpreted. The fact that both exhibit a maximal amplitude at relatively small angles seems to indicate the participation of rather large structural domains.

Adenosine Triphosphate↗

Estimation of local cerebral glucose utilization by positron emission tomography of [18F]2-fluoro-2-deoxy-D-glucose: a critical appraisal of optimization procedures.

Various approaches estimating local cerebral glucose utilization by positron emission tomography of labeled deoxyglucose are compared. Autoradiographic methods that predict the glucose utilization rate from a single scan are unreliable in pathologic tissue because of abnormal values of the model rate constants. A normalization procedure using the ratio of measured tissue activity to activity calculated with standard rate constants is proposed to readjust the values of the rate constants. Reliable estimates of metabolic rates can be obtained from dynamic recordings of tracer uptake. In the graphic approach, metabolic rate can be derived from the slope of a segment of a transformed uptake curve, which becomes linear at 15-20 min after intravenous tracer injection, with an accuracy comparable with that in complete dynamic studies. However, by recording and analyzing full-length uptake curves, in addition to metabolic rate, the model rate constants can be determined regionally. The physiological significance of those parameters is demonstrated in crossed cerebellar deactivation in 30 patients with supratentorial infarcts. Mild hypometabolism both within the ischemic lesion and in the morphologically intact cerebellum is accompanied by a reduction of the phosphorylation rate only. Severe metabolic depression, by contrast, affects both cerebellar transport and phosphorylation processes, whereas in the cerebrum, only the rate constant k1 is significantly correlated with the degree of metabolic disturbance.

Autoradiography↗

Repair of defined single base-pair mismatches in Escherichia coli.

Heteroduplexes with single base-pair mismatches of known sequence were prepared by annealing separated strands of bacteriophage lambda DNA and used to transfect Escherichia coli. Each of the eight possible single base-pair mismatches was constructed. Genetic analysis of the progeny phages obtained from transfected bacteria indicates that the E. coli mismatch repair system does not recognize (or does not repair) all single base-pair mismatches with equal efficiency. In particular, the A.G, C.T, and C.C mismatches appear to be less repaired than any others. The mutator character of mismatch repair-deficient mutants suggests that such unrepaired mismatches should occur infrequently during E. coli DNA replication.

Journal Article↗

In vivo and in vitro inhibition of B16 melanoma growth by vitamin B6.

The effect of vitamin B6 on the growth of B16 melanoma cells in vivo and in vitro was studied. B16 melanoma cells grown for three days in medium supplemented with 5.0 mM pyridoxine or 0.5 mM pyridoxal showed an 80% reduction in cell proliferation compared with control culture. Cells cultured for six hours in medium supplemented with 0.5 mM pyridoxal took up and incorporated 13 and 32% less [3H]thymidine, respectively, than did control cultures. A 17% reduction in [3H]glucose uptake was observed at this time point. When the incubation time was decreased to three hours, an inhibition of cellular uptake of [3H]thymidine (22%), [3H]uridine (14%), and [3H]glucose (15%) was observed; however, little or no inhibition in incorporation was detected. In in vivo studies, mice pretreated with pyridoxal for two weeks and then injected with B16 melanoma cells had a 62% reduction in tumor weight compared with controls at the end of a three-week period. If tumors were first established in mice and then treated with pyridoxal for six days, a 39% reduction in tumor growth was observed. There were no differences observed in body weights or liver weights in any of the animal groups. These results indicate that supraphysiological doses of vitamin B6 can inhibit the growth of B16 melanoma cells both in vitro and in vivo. The exact mechanism by which pyridoxal exerts its inhibitory effect was not ascertained, but experiments suggest that the vitamer may be acting on the plasma membrane to reduce precursor transport into the cell.

Adenosine Triphosphate↗

[In-vitro induced histamine liberation from mucous membrane of the stomach and duodenum before and following vagotomy].

In 13 patients suffering from duodenal ulcer and undergoing vagotomy biopsies were taken from mucosa of the gastric fundus and of the duodenum. Histamine release from the samples upon challenge to different food was assayed before and after vagotomy. Generally, more histamine was set free from gastric mucosa than from the duodenal one. However, in 11 of 13 subjects there was an alternative shift in the fundus and in the duodenum after vagotomy.

Adult↗

[Familial occurrence of cardiac myxomas].

A report is given on the occurrence of left atrial myxoma in both mother and daughter. A successful operation for a local recurrence was performed on the mother 4 years later. Sudden death of unknown cause occurred at young age in other siblings and was accompanied in one by arterial embolism, suggesting an even higher incidence. The potential accumulation of cardiac myxomas in a family was confirmed by a literature survey of 8 "myxoma families". Observation of these cases calls for the following Careful surgical excision because of the danger of a local recurrence. Echocardiographic follow-up for at least 5 years. Investigation of relatives.

Adolescent↗

Comparison of the effects of 15 and 60 micrograms/kg fentanyl used for induction of anesthesia in patients with coronary artery disease.

We compared the effects of 15 and 60 micrograms/kg fentanyl used for induction in 40 patients, 50-72 yr old, with coronary artery disease and mildly impaired ventricular contractility. Morphine (0.1 mg/kg) and scopolamine (0.4 mg) were used for premedication. Crystalloid (500 ml) was administered before induction, and nitroglycerin (0.3 micrograms X kg-1 X min-1) was infused during the study. Fentanyl, 15 or 60 micrograms/kg, was administered at a rate of 1.2 micrograms X kg-1 X sec-1. Pancuronium (0.04 mg/kg) and metocurine (0.16 mg/kg) were used for muscle relaxation. Data were collected 2 min before induction (baseline), before intubation (3 min), at 6 min, and at 13 min. Responses to 15 and 60 micrograms/kg were similar. At 3 min the heart rate (HR) in patients given 15 micrograms/kg increased by 6; whereas the HR in those given 60 micrograms/kg increased by 14 (P less than 0.01). Subsequent differences in HR were not significant. There were no dose-related differences in mean arterial pressure, cardiac index, central venous pressure, or pulmonary capillary wedge pressure. The EEG showed high-voltage low-frequency activity within 2 min in all patients. Arterial plasma fentanyl concentrations at 3 min averaged 25.9 +/- 3.8 ng/ml with 15 micrograms/kg and 89.9 +/- 15.2 ng/ml with 60 micrograms/kg. At 4 hr, plasma concentrations averaged 0.4 +/- 0.2 ng/ml and 3.6 +/- 0.7 ng/ml, respectively. We conclude that anesthesia for induction and intubation is achieved by the rapid administration of 15 micrograms/kg fentanyl and that 60 micrograms/kg has no substantially different effect on cardiovascular responses.

Aged↗

[Dose-dependent effect of amrinone on hemodynamics, myocardial circulation and myocardial energy requirement. An experimental study].

This study was designed to assess the dose-dependent effects of amrinone (1, 2 and 4 mg/kg i.v.) on hemodynamics, myocardial blood flow and myocardial oxygen consumption in anesthetised closed chest dogs (n = 8). Heart rate (HR), cardiac output, mean aortic pressure (MAP), left ventricular end-diastolic pressure (LVEDP), maximum dp/dt (dp/dtmax), myocardial blood flow (MBF) and aorto-coronary sinus oxygen difference (AVDO2 cor) were measured. Cardiac index (CI), stroke volume index (SVI), ejection fraction (EF), total peripheral resistance (TPR), coronary vascular resistance (CVR) and myocardial oxygen consumption (MVO2) were calculated from standard formulas. Amrinone improved myocardial pump function by a direct positive inotropic effect on the myocardium. EF and SVI increased to a maximal degree with 1 mg/kg amrinone (28% resp. 30%). dp/dtmax increased dose dependent (46, 64, 71%). Following a systemic vasodilation due to amrinone, left ventricular filling pressure and TPR decreased significantly. With 1 and 2 mg/kg amrinone MAP remained unchanged. 4 mg/kg produced a distinct fall in MAP accompanied by an increase in HR. The improvement in myocardial contractility did not cause a comparable increase of myocardial oxygen consumption. Due to an unloading of the heart 1 and 2 mg/kg amrinone induced no significant and prolonged augmentation of the myocardial oxygen demand. In the coronary circulation a non energy dependent vasodilation occurred followed by a marked decrease of AVDO2 cor (10, 18, 28%).

Aminopyridines↗