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Biomedical subjects

M Geiger

Publications and source records attributed to M Geiger.

At least 91 records · Page 5Linked to original sources
PubMed1988

Modification of a left-sided accessory atrioventricular pathway by radiofrequency current using a bipolar epicardial-endocardial electrode configuration.

Transcatheter ablation of a left posterolateral free wall accessory atrioventricular pathway using radiofrequency current and a bipolar epicardial-endocardial electrode configuration was attempted in a 19-year-old woman. The patient had suffered from recurrent syncope due to atrial fibrillation with rapid conduction to the ventricles. Following applications of radiofrequency current between one electrode in the coronary sinus and another in the left ventricle placed high against the mitral annulus, the anterograde effective refractory period was increased from less than 205 ms to a lasting value of 460 ms. Radiofrequency application could be performed without general anaesthesia and caused no side-effects.

Adult↗
PubMed1988

Competition of activated protein C and urokinase for a heparin-dependent inhibitor.

Human urine contains a hitherto unrecognized heparin-dependent inhibitor of activated protein C (APC) (Mr approximately 50,000) that coelutes from heparin-Sepharose together with the only observed peak of urokinase inhibitory activity at a position (0.35 M NaCl) similar to that of plasma protein C (PC) inhibitor. Based on functional assays and immunoblot studies, urokinase and APC compete for this crude inhibitor in the absence or presence of heparin. These results suggest that the same heparin-dependent urinary inhibitor that is immunologically different from several known protease inhibitors is responsible for the observed inhibition of APC and urokinase. In the absence of heparin this inhibitor inhibits APC and urokinase with similar rates, and heparin enhances its inhibitory activity toward both enzymes with more pronounced stimulation of its PC inhibitory activity than its urokinase inhibitory activity. Half-maximal stimulation of inhibition of APC occurs at about 2 mU/ml and maximal stimulation (approximately 10-fold increase of the pseudo-first-order rate constant) at greater than or equal to 50 mU/ml of heparin. This is the first demonstration of competition between APC and urokinase for a heparin-dependent inhibitor. These results may therefore represent a new link between the two major antithrombotic pathways, the PC pathway and the fibrinolytic system.

Chromatography, Affinity↗
PubMed1988

Plasminogen activation in diabetes mellitus. Kinetics of plasmin formation with tissue plasminogen activator and plasminogen from individual diabetic donors and with in vitro glucosylated plasminogen.

Functional abnormalities of tissue plasminogen activator (t-PA) (high Km in the presence of fibrin) and plasminogen (Pg) (substrate inhibition in the fibrin-stimulated system) from uncontrolled type I diabetics are reversible upon normalization of metabolic parameters. Therefore the effect of in vitro glucosylation of Pg was studied and similar but less pronounced substrate inhibition as with diabetic Pg was observed. However, the activation of the Pg fraction most likely containing bound cis-OH groups (e.g. glucose) was normal. These data suggest that either glucosylation in vitro is less stable than in vivo or that in diabetics protein modifications other than glucosylation occur. In this respect we can also show that acetone, a representative of ketone bodies and also elevated in poorly controlled diabetics, does not affect Pg activation in vitro.

Diabetes Mellitus, Type 1↗
PubMed1987

Immunological identity of heparin-dependent plasma and urinary protein C inhibitor and plasminogen activator inhibitor-3.

Purified plasma and urinary protein C inhibitors (PCI) formed heparin-dependent complexes with activated protein C (APC) which were detected by immunoblotting after nondenaturing gel electrophoresis. Bands representing APC.PCI complexes were also seen on immunoblots after incubation of plasma with APC and heparin. The same immunoblot pattern of complexes was detected by three different methods: method A, monoclonal antibody to plasminogen activator inhibitor-3 (PAI-3, urinary urokinase inhibitor) + 125I-labeled anti-mouse IgG; method B, polyclonal antibodies to PCI + 125I-labeled purified plasma PCI; and method C, monoclonal antibody to protein C + 125I-protein C. Plasma depleted of PAI-3 by immunoadsorption with insolubilized monoclonal antibody to PAI-3 showed no detectable antigen or complexes with APC as visualized by methods A or B. This PAI-3-depleted plasma had less than 10% of the heparin-dependent inhibitory activity of normal plasma toward APC. Purified plasma PCI was fully reactive in an enzyme-linked immunoabsorbent assay for PAI-3, and plasma and urinary PCI inhibited urokinase activity in a heparin-dependent manner. These data indicate that heparin-dependent plasma and urinary PCI and PAI-3 are immunologically and functionally very similar if not identical. This observation identifies a new interrelation between the protein C anticoagulant and the fibrinolytic systems. In addition, plasma contains a heparin-independent inhibitor of APC which is not immunologically related to plasma PCI or to PAI-3.

Antibodies, Monoclonal↗
PubMed1987

Tissue-type plasminogen activator and urokinase: differences in the reaction pattern with the active-site titrant 4-methylumbelliferyl-p-guanidinobenzoate hydrochloride.

The applicability of 4-methylumbelliferyl-p-guanidinobenzoate hydrochloride (MUGB) as active-site titrant for tissue-type plasminogen activator (t-PA) was studied in comparison to urokinase. Although t-PA was capable of cleaving MUGB, active-site titration of t-PA (one-chain form as well as two-chain form) with MUGB was not possible, whereas MUGB titration of urokinase could be performed. We therefore studied the kinetics of the interaction of these two plasminogen activators with MUGB. The equilibrium dissociation constant, KS, for the interaction between MUGB and urokinase was 2.9 X 10(-6) M, and for the interaction with t-PA 3.13 X 10(-5) M. However, one main requirement for active-site titration, namely a stable acyl enzyme intermediate (ES'), was only fulfilled for MUGB urokinase but not for MUGB t-PA. Whereas for the reaction of MUGB and urokinase the first-order acylation rate constant k2 was found to be about 10(6)-times higher than the first-order deacylation rate constant k3 (k2 = 3.76 X 10(-1) s-1, k3 = 3.7 X 10(-7) s-1), the k2/k3 ratio for the reaction of MUGB and t-PA (one- and two-chain form) was 0.77 to 3.85. Therefore, urokinase and t-PA differ in their reaction with this fluorogenic substrate and MUGB cannot be used for active-site titration of tPA.

Binding Sites↗
PubMed1987

Programmed electrical stimulation in patients with hypertrophic cardiomyopathy.

Programmed electrical stimulation was performed in 54 consecutive patients with hypertrophic cardiomyopathy. Three patients had a history of cardiac arrest due to ventricular tachyarrhythmias (group A), eight patients had a history of syncope of unknown origin (group B), and 43 patients were "asymptomatic", i.e. they had no documented or suspected symptomatic ventricular arrhythmias (group C). There were no differences among the groups with respect to electrocardiographic, echocardiographic or hemodynamic data. Ventricular arrhythmias were induced by atrial and right and left ventricular stimulation with a maximum of two extrastimuli in 18 patients. Induced arrhythmias were repetitive ventricular response in six patients, nonsustained ventricular tachycardia in four, sustained ventricular tachycardia in five, and ventricular fibrillation in three patients. Ventricular tachycardia was always rapid with a mean cycle length of 194 +/- 20 ms. In one group A patient, rapid ventricular tachycardia was induced during atrial stimulation. The type and incidence of induced ventricular arrhythmias did not differ among the three groups. It is concluded that programmed stimulation with a maximum of two ventricular extrastimuli cannot distinguish between patients with hypertrophic cardiomyopathy who had either cardiac arrest or syncope or were "asymptomatic".

Cardiac Pacing, Artificial↗
PubMed1986

Nonenzymatic glucosylation as a contributing factor to defective fibrinolysis in diabetes mellitus.

Kinetics of activation of plasminogen purified from the plasma of 3 uncontrolled diabetic patients by tissue type plasminogen activator revealed substrate inhibition in the fibrin-stimulated system. After improvement of metabolic parameters activation of plasminogen was found to be normal in 1 of these patients and partially improved in another patient. Studies performed to investigate a possible nonenzymatic glucosylation of plasminogen showed that purified control plasminogen incorporates 14C-glucose in a dose- and time-dependent manner and that in vitro glucosylation of control plasminogen results in functional abnormalities of plasminogen, which resemble those observed with plasminogen from diabetic patients as far as substrate inhibition in the fibrin-stimulated system is concerned.

Carbon Radioisotopes↗
PubMed1985

Plasminogen activation in diabetes mellitus: normalization of blood sugar levels improves impaired enzyme kinetics in vitro.

We have demonstrated previously that fibrin enhanced plasmin formation by the vascular plasminogen activator was significantly impaired, when components isolated from the plasma of three uncontrolled diabetic patients (type I) were used to study plasminogen activation in vitro. In the present study it can be demonstrated that functional properties of the vascular plasminogen activators as well as of the plasminogens from the same three diabetic patients are significantly improved after normalization of blood sugar levels and improvement of HbA1c values. Most pronounced the Km of diabetic vascular plasminogen activator in the presence of fibrin returned to normal values, and for diabetic plasminogen the prolonged lag period until maximal plasmin formation occurred was shortened to almost control values. From these data we conclude that the observed abnormalities of in vitro fibrinolysis are not primarily associated with the diabetic disease, but might be secondary to metabolic disorders caused by diabetes.

Adult↗
PubMed1985

Hypertrophic cardiomyopathy: non-invasive assessment of diastolic and systolic functional parameters in relation to heart rate.

Hypertrophic cardiomyopathy (HC) is characterized by reduced left ventricular compliance and subsequent filling abnormalities. To study the pathophysiologic changes in parameters of left ventricular systolic and diastolic performance as a function of increasing heart rate 14 patients with HC (32 +/- 12 yrs; 11 M, 4 F) and 4 normal individuals were subjected to equilibrium radionuclide ventriculography (99mTc-labelled red blood cells) at rest and during incremental right atrial pacing; heart rate was increased in steps of 20 beats per min from basal state to the individual symptom-limited endpoint. Mean symptom-limited heart rate was 141 +/- 28 in HC and 160 in normals (p less than .01.). At each pacing level filling and ejection parameters as well as the left ventricular endsystolic (LVESV) and enddiastolic volume (LVEDV) were determined relative to resting volumes at a heart rate of 78 +/- 8. At the individual maximal pacing rate HC revealed a decline in LVEDV to 61 +/- 4% (p less than .001) and an increase in LVESV to 117 +/- 14% (p less than .001) resulting in decreasing ejection fractions at heart rates above 120. Peak LV filling rates initially increased but subsequently decreased steeply at heart rates above 100; peak LV ejection rates in HC showed a similar pattern with increasing frequency. Time intervals to peak ejection and peak filling rate did not differ from normal. Thus, patients with HC demonstrated combined left ventricular diastolic and systolic abnormalities with increasing heart rate leading into a low-input low-output circulatory state. This probably explains not only the symptoms associated with HC, but also supports the concept of "hemodynamic syncope" in HC.

Adolescent↗
PubMed1984

Plasminogen activation in diabetes mellitus. Kinetic analysis of plasmin formation using components isolated from the plasma of diabetic donors.

Two components of the fibrinolytic system, plasminogen and the vascular plasminogen activator, have been isolated to apparent homogeneity from the post-venous occlusion plasma of three diabetic patients (hemoglobin A1C greater than 7%) and of one nondiabetic control person. Plasminogen activation was studied for each person separately in the absence and presence of CNBr fragments of fibrinogen. Activation of diabetic plasminogen by urokinase was not significantly altered as compared to the activation of control plasminogen. The same was found when diabetic plasminogen was activated by control vascular plasminogen activator in the presence of fibrinogen fragments but only at plasminogen concentrations below 10-30 nM; at higher substrate concentrations, however, plasminogen activation was impaired in a pattern resembling substrate inhibition. Activation of control plasminogen by diabetic vascular plasminogen activator was completely impaired in the absence of fibrinogen fragments. Addition of fibrinogen fragments stimulated plasmin formation by diabetic vascular plasminogen activator resulting in kinetic constants which were similar to the activation of control plasminogen by control vascular plasminogen activator in the absence of fibrinogen fragments (Km = 7.5 microM, kcat = 0.05 S-1). Addition of fibrinogen fragments in controls decreased Km values to less than 0.1 microM. Despite addition of fibrinogen fragments the rate of plasmin formation from diabetic plasminogen by diabetic vascular plasminogen activator isolated from the same diabetic donor was so small that kinetic constants could not be calculated.

Diabetes Mellitus↗
PubMed1982

[Exercise-induced asthma and arterial hypoxemia].

40 young asthmatic patients performed submaximal work on a treadmill ergometer for 6 minutes. In 20 cases the PaO2 was found to be below 77.5 mm Hg (arterial hypoxemia) at the 10th or the 20th minute of post-exercise recovery time. A first subgroup A of 9 asthmatics presented hypoxemia together with a fall of FEV1 below 90% of control at the first to the 20th minute post-exercise recovery phase. A second subgroup B of 11 asthmatics showed hypoxemia with FEV1's higher than 90%, often higher than 100% of the control value. The following features of the recovery period were observed: 1. 10 minutes delay of onset of hypoxemia in relation to the FEV1 drop in group A. 2. Progressive hypoxemia despite a clear return of FEV1 versus the control value during the late recovery phase of group A. 3. Appearance of arterial hypoxemia despite unchanged normal FEV1's in group B. These three observations suggest that there are 2 kinds of post-exercise bronchoconstrictions. The first may be situated in the large bronchi (FEV1-drop), the second in the small peripheral airways (PaO2-drop), from the first to the 20th and from the 20th to the 40th minute respectively after the end of submaximal work load. It is concluded that there must be 2 sequential bronchoconstrictions due to cooling of the airways and these constrictions may guarantee alveolar homeostasis for body temperature and full saturation with water vapour. However, the first barrier in the large airways can be abolished by high blood levels of adrenaline. In such cases the second barrier in the small airways becomes important and may protect the alveoli from cooling and dry air.

Adult↗
PubMed1976

Membrane SH-groups related to adrenaline action in rat adipocytes: a comparative study using sulfhydryl reagents of different molecular size.

The orientation of SH-groups within the fat cell membrane involved in adrenaline (and NaF) action was studied by comparing the effects of uncoupled p-CMB with those of a large derivative of this reagent -- p-CMB-dextran --. Preincubation of intact adipocytes with uncoupled p-CMB caused a dose-dependent inhibition of adrenaline (and NaF) stimulated adenylate cyclase activity as determined in ghosts prepared subsequently. Preincubation with p-CMB-dextran, however, influenced neither the lipolytic response to adrenaline nor the catecholamine (and NaF) activated adenylate cyclase activity. When p-CMB-dextran was present during ghost preparation, a dose-dependent inhibition of adrenaline (and NaF) stimulated adenylate cyclase activity was observed. These results suggest that the binding sites of adrenaline as well as SH-groups essential for activity of adenylate cyclase are not localized near enough to the exterior surface to be accessible for p-CMB-dextran. The polarity in the sensitivity of fat cell adenylate cyclase could not be observed when p-CMB-dextran was added directly to intact or fragmented ghosts. The abbreviations used are: Cyclic AMP, cyclic adenosine 3',5'-monophosphate; p-CMB, p-chloromercuribenzoate.

Adenylyl Cyclases↗