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Biomedical subjects

W Vogt

Publications and source records attributed to W Vogt.

At least 127 records · Page 7Linked to original sources

Is the determination of serum digoxin concentration useful for the diagnosis of digitalis toxicity?

In a prospective symptom-oriented study, patients with (n = 81) or without (n = 206) digoxin toxicity were not discernible on their serum digoxin concentration (SDC) because of a large overlap between toxic and non-toxic groups. There was, however, a significant difference between the mean values of the groups (p < 0,01). Serum creatinine, the presence or absence of ischemic heart disease, and/or chronic pulmonary heart disease were significantly different (both p < 0,025) between toxic and non-toxic groups. It is concluded that a decision on digitalis toxicity should be made by a synopsis of the influencing factors in the individual case. Dosage, serum creatinine and cardiac status seem to be the most important factors to be taken into account. Lack of agreement between SDC and digoxin effects could be demonstrated in differences in "T 1/2" between SDC and the normalisation of prolonged PQ-time after digoxin withdrawal. The inability of the SDC to describe all alterations important for digitalis effects and side effects seems to be that it does neither mirror the glycoside concentration at the receptor site, nor the changes of receptor affinity, nor the changes of (Na+ + K+)-ATPase activity.

Aged↗

Activation of human lymphocyte subpopulations by protein A from Staphylococcus aureus bacteria.

Cowan I strain Staphylococcus aureus bacteria were found to be mitogenic for human peripheral and cord blood lymphocytes. Experiments with lymphocyte supopulations otained by nylon wool filtration and/or E-rosette separation revealed that T-lymphocytes are the main target cells, whereas isolated B cells did not respond significantly. Further experiments suggested that B cells could be activated in the presence of mitomycin-treated T cells. Null cell-enriched lymphocyte suspensions could be stimulated by Con A but not by the bacteria or by PHA.

B-Lymphocytes↗

Incompatibility between complement components C3 and C5 of guinea-pig and man, an indication of their interaction in C5 activation by classical and alternative C5 convertases.

The use of heterologous combinations of guinea-pig and human complement components for titration of C5 with convertases of the alternative and classical pathway has been investigated. In addition to the known unfavourable combination of C2hu with C4gp partial incompatibilities were detected between heterologous C3 and C5 as well as between CZhu and C5gp. The incompatibility between heterologous C3 and C5 is of special interest since it indicates an interaction of these two non-enzymic components. Concomitant binding studies have demonstrated that a reduced efficiency of C5 convertases correlates with decreased binding affinity of surface-fixed C3b for C5 when heterologous components are offered. Hence, the present studies give further evidence that surface-bound C3b has the function of a co-factor which binds C5; this interaction is required for C5 activation via the classical as well as the alternative pathway, i.e. by the C3/C5 convertases C42 and C3bB.

Animals↗

[Determination of thyroxine in serum by a heterogeneous enzyme immunoassay: results of a joint trial].

This paper describes the evaluation of a heterologous enzyme immunoassay for the determination of total thyroxine in serum by a group of seven clinical chemical laboratories. The test follows the principles of the enzyme linked immunosorbent assay (ELISA) and uses peroxidase as a marker. The evaluation of analytical reliability yielded the following results within the analytical range from 39 unto 322 nmol/l: 1. Within-batch precision ranged from 3.1 unto 10.4% (coefficient of variation) with single analyses. 2. Between-batch precision ranged from 3.7 unto 20.4% with single analyses. 3. Between-laboratories precision ranged from 5.4 unto 6.8%. 4. Pure thyroxine, added to serum or thyroxine-free serum, gave recoveries between 93 and 120%. 5. Analysis of control sera gave results essentially comparable to the assigned values based upon radioimmunoassays. 6. Analysis of 288 clinical sera gave slightly higher results by the enzyme immunoassay than by the analogous radioimmunoassay from the same manufacturer. 7. Comparison with other methods of analysis (radioimmunoassays, competitive protein ligand assays, hormonal iodine assay) yielded partly comparable, partly higher results. 8. Comparison with the homogenous enzyme immunoassay (EMIT) led to comparable results. 9. Interference due to hyperlipemia or hemolysis was not observed. 10. There might be an interference in hyperbilirubinaemic sera, due to an as yet unknown factor. With respect to practicability the ELISA-test compares favourably with the analogous solid phase radioimmunoassay. The main differences are the absence of radioactive material and a longer shelf-live of reagents. Following the manual procedure the time taken to perform the enzyme immunoassay is slightly longer than for the analogous radioimmunoassay.

Enzyme-Linked Immunosorbent Assay↗

Multiple effects of a diamidine (propamidine) on complement activation.

Propamidine, one of the diamidines used against infections with babesiae has inhibitory and enhancing effects on complement activation as assessed by immune haemolysis of sensitized sheep red cells. Utilization of C1 is powerfully, that of C3 weakly improved by propamidine while activation and/or fixation of C4, C5 and to a lesser degree of C8 and C9 are inhibited. At low concentrations of propamidine (less than 2 mM) the enhancing effects, at higher concentrations the inhibitory effects predominate. Inhibition is produced, in some cases certainly, in others likely, by interference of propamidine with binding properties of complement components. None of the complement enzymes, C1s, C42 or C3bBb was inhibited in its hydrolytic activity. The possible significance of propamidine actions is discussed.

Amidines↗

Interference of propamidine with binding of the fifth component of complement to surface-fixed C3b, and with C5 activation.

The effects of propamidine and their dose dependency, on utilization of the third and fifth complement components in immune haemolysis have been compared. While C3 utilization is not disturbed that of C5 is markedly inhibited by propamidine in concentrations as low as 0.5 mM. Both, binding of C5 to surface-fixed C3b and cleavage of C5 by convertases C42 and C3bBb, are also inhibited in the presence of propamidine. Since neither C3 cleavage by these enzymes nor even C5 cleavage by the cobra venom factor-supported convertase CFVBb is significantly reduced a general convertase-inhibiting effect of propamidine is ruled out. Rather the effect on utilization of C5 is the result of interference with binding of C5 is the result of interference with binding of C5 to C3b and hence impairment of its accessibility to the convertases. These findings thus further support the role of surface fixed C3b in C5 activation proposed earlier.

Amidines↗

Substrate modulation as a control mechanism in the activation of plasma multienzyme systems.

Since plasma is a homogenous fluid its biochemical systems need special control mechanisms to prevent their unlimited and continuous activity. In general, enzymic activity is not preformed but generated by trigger processes. Activation is then enhanced by cascade reactions. It can be controlled by enzyme inhibitors, by enzymes which destroy co-factors, or by spontaneous decay or enzyme complexes involved in the system. In addition, in some reactions of the complement and Hageman factor-dependent systems the necessity of substrate modulation controls the extent of activation. Thus, factor B of the properdin system is activatable by factor D only when bound to the activated third component of complement, and C3b fragment; similarly C2 is activated and forms the C3 converting complex, C42, only when bound to C4b prior to its cleavage by C1; C5 can be activated by either of the two convertases only when bound to surface-fixed C3b; and the mutural activation of Hageman factor and pre-kallikrein on surfaces proceeds efficiently only when HMW-kininogen is present which complexes with pre-kallikrein and possibly with Hageman factor.

Complement C3↗

Quantitation of adrenaline and noradrenaline from human plasma by combined gas chromatography--high-resolution mass fragmentography.

A gas chromatographic--high-resolution mass fragmentographic method for the simultaneous determination of adrenaline and noradrenaline from human plasma is presented. The catecholamines are separted by adsorption on alumina and converted by a selective, two-step procedure to the corresponding N-trifluoroacetyl-N-trimethylsilyl derivatives. The benzylic fragment C16H31O3Si3 (m/e 355.1568) of these derivatives is detected at a mass spectrometric resolving power of 5000. This high resolution detection was necessary to differentiate this fragment from others with the same nominal mass of 355 originating from the biological matrix and/or the bleeding from column and septum.

Epinephrine↗

Performance of various mathematical methods for computer-aided processing of radioimmunoassay results.

Interpolation and regression methods are available for computer aided determination of radioimmunological end results. We compared the performance of 6 algorithms (weighted and unweighted linear logit log regression; quadratic logit log regression, smoothing spline interpolation with a large and small smoothing factor, respectively, and polygonal interpolation and the manual curve fitting on the basis of three radioimmunoassays with different reference curve characteristics (digoxin, estriol, human chorionic somatomammotrophin (HCS)). Great store was set by the accuracy of the approximation at the intermediate points on the curve, i.e. those points that lie midway between two standard concentrations. These concentrations were obtained by weighing and inserted as unknown samples. In the case of digoxin and estriol the polygonal interpolation provided the best results, while the weighted logit log regression proved superior in the case of HCS.

Computers↗

Mass spectrometry of dimethylthiophosphinates of aromatic hydroxy compounds.

The mass spectra of 20 differently substituted dimethylthiophosphinic esters of aromatic hydroxy compounds are presented. Fragmentation routes were investigated using high resolution mass measurements, decoupled metastable determinations and deuterium labelling. All compounds exhibited abundant molecular ions and typical phosphorus-containing ions. Characteristic elimination processes strongly dependent upon the respective type of substitution were observed. Due to their high stability, their great ease of formation and their good gas chromatographic properties these new types of derivatives are of special interest for establishing gas chromatography mass spectrometry profiles of acidic catecholamine metabolites.

Gas Chromatography-Mass Spectrometry↗

Chemotactic effects of the complement-derived peptides C3a, C3ai and C5a (classical anaphylatoxin) on rabbit and guinea-pig polymorphonuclear leukocytes.

The complement-derived peptides C3a, C3ai and C5a (= classical anaphylatoxin) were purified from hog serum and examined for chemotactic activity on rabbit and guinea-pig polymorphonuclear leukocytes (PMN) with the Boyden chamber technique (with filters of 3,0 micrometer pore size). When media containing albumin or serum were used all peptides induced chemotaxis of both cell species. Only C3a showed a pronounced species dependence in that it was much more active on rabbit than on guinea-pig PMN. No gross differences were found between the influence of 0.5% BSA and 10% heated (56 degree, 30 min) homologous serum added to the medium. In the absence of protein chemotaxis did not occur.

Anaphylatoxins↗

Indomethacin treatment of acute experimental pancreatitis in the rat.

Indomethacin given orally or intramuscularly before or shortly after induction of acute sodium-taurocholate or olive-oil-induced pancreatitis in rats reduced the lethality. Neither the enzyme content of serum, ascites, and pancreatic tissue nor the damage to the organ itself were changed under the influence of indomethacin. Thus a modification of systemic effects of acute pancreatitis may be responsible for the beneficial effect of indomethacin.

Acute Disease↗

Activation of lymphocyte subpopulations in patients with chronic lymphocytic leukemia.

T lymphocytes from the peripheral blood of normal donors and patients with CLL were isolated by nylon wool filtration or E-rosette separation and tested for functional activities. Unseparated CLL lymphocytes showed a poor response to phytomitogens and to allogeneic cells. Subpopulations enriched in E-RFC showed an increased PHA- and a normal MLC-reactivity; the Con A responses, however, were markedly reduced in all experiments. Subpopulations which were T cell depleted showed no reactivity to all mitogens. Purified T cells from normal donors showed a decreased reactivity to PHA, Con A and PWM. The Con A responses were completely abolished in almost all experiments. These diminished responses could be restored by unseparated cells or by small numbers of syngeneic, mitomycin-treated monocytes. The data suggest that mitogen-induced T lymphocyte stimulation in vitro in general depends on the presence of monocytes.

Antibody-Producing Cells↗

[Cardiac effects of antikaliuretic diuretics-clinical and biochemical investigation (author's transl)].

Recently direct myocardial effects of antikaliuretic diuretics with respect to contractility parameters and prevention of digitalis-induced arrhythmias were published. In order to test the value of these reports we measured the effect of potassium-canrenoate and triamterene on cardiac output and on digitalis-induced arrhythmias in patients during diagnostic and the therapeutic flow directed right heart catheterization (Swan-Ganz) in our intensive care unit. In addition the influence of these drugs on (Na+ + K+)-ATPase and on (3H)g-strophanthin binding to human cardiac cell membranes was investigated to gain information on the mechanism of their action. Triamterene (100-200 mg p.o.) was without any effect on cardiac output, the same was found true for potassium-canrenoate given in a single dose (200-1000 mg intravenously). However, when applied in two doses (200 mg i.v. and 60 min later 400 mg i.v.), potassium-canrenoate increased cardiac output by 11 percent (p less than 0.05). Only in 2 out of 14 patients potassium-canrenoate (200-400 mg i.v.) suppressed digitalis-induced ventricular ectopic beats. Canrenone, the active metabolite of potassium-canrenoate displaces [(3H)]g-strophanthin from its binding sites in human cardiac cell membranes and inhibits (Na+ + K+)-ATPase activity. These in vitro effects were measured at the same concentrations as found in vivo after "therapeutical" doses. The effects of triamterene in this respect were found only in extremely high concentrations. Our results imply that canrenone has cardiac glycoside-like effects in human cardiac cell membranes.

Adenosine Triphosphatases↗

[Effect of total fasting on serum protein concentrations (author's transl)].

During a period of total fasting restricted to three weeks, haptoglobin, transferrin and beta1A-globin showed a marked, continuous decline. The complement was finally distinctly below the reference range. Macroglobulins and coeruloplasmin rised until the tenth day and decreased thereafter. IgG globulin remained essentially unchanged while immunoglobulins gammaA and gammaM showed an increase. On account of the considerable fluctuations observed in the protein fractions fasting in this form at least beyond a period of 21 days does not seem justified.

Blood Proteins↗