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Biomedical subjects

G Noll

Publications and source records attributed to G Noll.

At least 109 records · Page 6Linked to original sources
PubMed1991

Different potency of endothelium-derived relaxing factors against thromboxane, endothelin, and potassium chloride in intramyocardial porcine coronary arteries.

Endothelium-derived relaxing factors (EDRFs) and prostacyclin (PGI2) released from endothelial cells are potent vasodilators; endothelin-1 and thromboxane A2 may be their physiological antagonists. Interactions between these vasodilators and vasoconstrictors were studied in isolated intramyocardial porcine coronary arteries suspended in myographs for isometric tension recording. Endothelium-dependent relaxations to bradykinin and serotonin were reduced to a similar extent in arteries contracted with endothelin-1 and KCl as compared to those contracted with the thromboxane analog U 46619 (p less than 0.05; n = 5-6). In contrast, relaxations to the nitric oxide donor SIN-1 were comparable. PGI2 was most potent in arteries exposed to U 46619, while its effects were inhibited in the presence of endothelin-1 or acetylcholine and prevented by KCl (p less than 0.05-0.0001; n = 5). At high concentrations PGI2 evoked contractions in arteries contracted with endothelin-1, acetylcholine, or KCl, but not in those with U 46619, which were prevented by the thromboxane receptor antagonist SQ 30741 (p less than 0.05; n = 5), indicating that PGI2 is a partial agonist for the thromboxane receptor. Thus, in intramyocardial porcine coronary arteries, contractile agonists differently interact with the release and action of EDRFs and PGI2. Both are most effective against contractions induced by thromboxane. In contrast, endothelin-1 and particularly KCl reduce the potency of these endogenous vasodilator systems.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1991

Oxidized low density lipoproteins inhibit relaxations of porcine coronary arteries. Role of scavenger receptor and endothelium-derived nitric oxide.

BACKGROUND: We studied the effects of low density lipoprotein (LDL) on endothelium function. METHODS AND RESULTS: Porcine epicardial and intramyocardial coronary arteries suspended in organ chambers for isometric tension recording were exposed to LDL for 2 hours and were then washed. In epicardial coronary arteries, oxidized LDL (30-300 micrograms/ml) but not native LDL or lysolecithin inhibited endothelium-dependent relaxations to serotonin, thrombin, and aggregating platelets (5,000-75,000/microliter). Endothelium-dependent relaxations to bradykinin and A23187 and endothelium-independent relaxations to SIN-1 were unaffected by oxidized LDL. In intramyocardial coronary arteries, oxidized LDL had no appreciable effect on relaxations to serotonin. The effect of oxidized LDL on the response to serotonin in epicardial coronary arteries was completely prevented by dextran sulfate (10 micrograms/ml). The inhibitory effect of oxidized LDL persisted in the presence of pertussis toxin. Similar to the lipoproteins, L-NG-monomethyl arginine (L-NMMA) reduced relaxations to serotonin but not to bradykinin in epicardial coronary arteries. In the presence of L-NMMA, oxidized LDL further reduced the response to serotonin. In arteries in which relaxations to serotonin were inhibited by oxidized LDL, L-arginine but not D-arginine induced a full relaxation. Pretreatment with L-arginine potentiated relaxations to serotonin in arteries exposed to oxidized LDL. CONCLUSIONS: Thus, oxidized LDL activates the scavenger receptor on endothelial cells and inhibits the receptor-operated nitric oxide formation in epicardial but not in intramyocardial coronary arteries. The mechanism is not related to dysfunction of a Gi protein but is related to a reduced intracellular availability of L-arginine. The reduced nitric oxide formation at sites of early atherosclerotic lesions may favor platelet aggregation and vasospasm, both of which are known clinical events in patients with coronary artery disease.

Animals↗
PubMed1991

Cerebral blood flow is not altered by treatment with nitrendipine in patients with mild to moderate hypertension.

We evaluated the effects of nitrendipine, a calcium antagonist of the dihydropyridine group, on cerebral blood flow (CBF) in nine patients with mild to moderate hypertension. The CBF was determined under placebo, 2 h after the first dose (short term) and after 4 weeks (long term) of regular nitrendipine treatment. The CBF was determined using the xenon-133 method. All patients were on placebo for 2-4 weeks before nitrendipine administration. The mean age was 48 years (range of 35-67 years). Blood pressure fell from 169 +/- 19/110 +/- 16 to 147 +/- 12/94 +/- 11 mm Hg after the first dose and to 140 +/- 12/92 +/- 9 mm Hg after long-term administration (p less than 0.01). The corresponding CBF did not change significantly from 37.5 +/- 4.8 ml/100 g/min before to 38.7 +/- 4.5 ml/100 g/min 2 h after the first dose and 38.1 +/- 6.0 ml/100 g/min after long-term administration of nitrendipine (p = 0.3 and p = 0.8, respectively). In conclusion, nitrendipine did not alter the CBF of mildly to moderately hypertensive patients. Particularly, the CBF was maintained during short-term and long-term administration despite significant blood pressure reduction.

Adult↗
PubMed1990

Carbohydrate structures of a human tissue plasminogen activator variant expressed in recombinant Chinese hamster ovary cells.

The carbohydrate structures of a genetically engineered human tissue plasminogen activator variant bearing a single N-glycosylation site at Asn 448 are reported. After isolation of the tryptic glycopeptide and liberation of the N-linked carbohydrates by polypeptide:N-glycosidase F, 6 major oligosaccharide fractions were separated by HPLC on NH2-bonded phase. Their structures were determined by compositional and methylation analyses combined with fast atom bombardment mass spectrometry. Seventy percent of the carbohydrates were of the biantennary complex type with fucose at the proximal GlcNAc and zero, one or two alpha 2-3 linked NeuAc. The remainder were triantennary structures with one, two or three NeuAc.

Animals↗
PubMed1988

Additional molsidomine in refractory unstable angina pectoris.

In a prospective single-blind study we examined the effects of additional molsidomine in 20 patients (63 +/- 10 years; 15 males, 5 females) with unstable resting angina (greater than or equal to 3 attacks/24 hours) refractory to triple therapy (nitrates, calcium antagonists, and beta blockers) combined with heparin or aspirin. All but one patient had coronary artery disease documented by coronarography (n = 17) or by recent myocardial infarction (n = 3). Two patients had angiographically documented severe coronary spasms. Patients entered the study if coronary bypass surgery or PTCA could not be performed within 3 days after angiography (n = 9) or was not feasible due to anatomical or technical reasons (n = 6), concomitant malignant disease (n = 2), or age greater than 75 years (n = 3). All patients received molsidomine orally 12 to 24 mg/day. In 15 of the 20 patients molsidomine was given i.v. initially, starting with 20 mg i.v., followed by infusion of 1 to 4 mg/hour. Heart rate and blood pressure did not change significantly, and eight patients had a slight decrease of systolic and diastolic blood pressure. Severe adverse effects did not occur, and moderate headaches were reported by five patients. In 13 patients, unstable angina could be stabilized, and they remained free of resting angina; five had a marked reduction of the frequency of anginal attacks. In two patients, molsidomine was without demonstrable beneficial effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Short- and long-term cerebrovascular effects of nitrendipine in hypertensive patients.

The aim of our studies was to evaluate the effect of acute treatment in hypertensive emergencies and of chronic and acute treatment in uncomplicated hypertensives with calcium antagonists on blood pressure (BP) and cerebral blood flow (CBF). Ten patients with high blood pressure requiring emergency reduction were randomized to treatment with oral nifedipine or intravenous clonidine. The effect on CBF was investigated using xenon-133. Twenty-one patients with mild to moderate hypertension were randomly assigned to nitrendipine (n = 10) and to verapamil treatment for 4 weeks. After 14 days of washout, all patients received chlorthalidone for 4 weeks. CBF was measured before calcium antagonists, after 4 weeks, after washout, and after 4 weeks of chlorthalidone. Until now, five patients with mild to moderate hypertension entered in an ongoing study. After 14 days of placebo, CBF and BP reduction were measured 2 h and 6 weeks after nitrendipine. In hypertensive emergencies, nifedipine and clonidine lowered BP significantly, whereas CBF increased after nifedipine and decreased after clonidine. After chronic treatment with nitrendipine and verapamil and after chlorthalidone, the BP-lowering effect was significant whereas CBF remained unchanged. Two hours after nitrendipine, BP decreased and CBF remained unchanged. The reason for increasing CBF in hypertensive emergencies after nifedipine is due to its spasmolytic effect on cerebral vessels. The unchanged CBF after short- and long-term treatment with nitrendipine is due to the fact that in these patients the autoregulatory mechanism is intact.

Adult↗
PubMed1986

Cytotoxic T cell lysis of H-2-negative murine sarcoma cells.

The DOH cell line was established from C3H.OH (H-2Kd,Dk) embryonic fibroblasts transformed with Rous sarcoma virus (RSV) in vitro. When injected into syngeneic mice, DOH cells were very weakly tumorigenic and induced a cytotoxic immune response. Cytotoxic T lymphocytes (CTL) specifically lysed DOH cells but not other RSV-induced sarcoma cells, which shared the H-2Kd or H-2Dk antigen, respectively, with DOH. Serological and immunochemical analysis of H-2 antigens subsequently showed that DOH sarcoma cells did not express syngeneic H-2K and H-2D antigens. Surprisingly, a H-2Kk-specific monoclonal antibody (100-5) bound to DOH cells and was inhibitory for syngeneic CTL specific for DOH. In addition, DOH cells were lysed by alloreactive H-2Kk-specific CTL. The demonstration of immunogenic H-2-negative sarcoma cells suggests that either the H-2K antigens have been extensively altered or that hitherto unidentified major histocompatibility complex class I molecules are expressed on DOH sarcoma cells surfaces, acting as target antigens for tumor-specific CTL.

Animals↗
PubMed1985

Treatment with stanozolol before thrombolysis in patients with arterial occlusions.

The administration of the anabolic steroid stanozolol during 7, 8 days as pretreatment before thrombolytic therapy of acute or subacute arterial occlusions enhances the fibrinolytic potential significantly. On average the plasminogen increased from 101% to 133%, the euglobulin lysis time after venous stasis was shortened and the alpha 2-antiplasmin remained constant. This effect could be favourable to prepare patients undergoing thrombolytic treatment.

Aged↗
PubMed1984

Plasmin inhibitors and fibrinogen breakdown during the initial phase of thrombolytic treatment--the problem of the alpha 2-antiplasmin determination.

During the first 3 hr of thrombolytic treatment with porcine plasmin (p-PL) or streptokinase (SK) a rapid decrease of clottable fibrinogen with generation of large amounts of fibrin(-ogen) degradation products (FDP) are found. alpha 2-antiplasmin (alpha 2AP) is rapidly neutralized. Whereas in patients treated with SK more than half of the original plasminogen was consumed, its level remained unchanged during p-PL infusion. When alpha 2AP reaches values below some 20%, spontaneous amidolytic activity towards S-2251 representing either PL-alpha 2-macroglobulin- or SK-plasminogen-complex activity appears. This activity has to be considered in the alpha 2AP assay in order to avoid underestimation of this inhibitor.

Animals↗
PubMed1984

In vitro effects of the acylated streptokinase-plasminogen activator complex BRL 33 575 incubated with normal human plasma.

Thrombolysis with acylated streptokinase-plasminogen complexes is aimed to achieve fibrinolysis without systemic fibrinogenolysis. The p-aminobenzoyl-streptokinase-(Lys)-plasminogen-complex (BRL 33 575) should be particularly useful due to its slow deacylation rate. Unexpectedly, repeated doses of 10 mg of BRL 33 575 (corresponding to 310'000 streptokinase equivalent units) induced systemic effects in patients though less than streptokinase alone. In vitro incubation of normal human plasma with BRL 33 575 at concentrations used in patients resulted in nearly complete consumption of alpha 2-antiplasmin and plasminogen and significant fibrinogenolysis within 3 hr. This demonstrates that - despite of slow deacylation of BRL 33 575 - the small amounts of activator generated are highly efficacious in activating plasma plasminogen under conditions in which no physiological clearance of the free activator takes place. Simulating the calculated activator release from BRL 33 575 by infusing equivalent amounts of streptokinase into plasma resulted in less pronounced effects. This is probably explained by anti-streptokinase antibodies which will neutralize the initially infused streptokinase but will be bound by BRL 33 575. Our in vitro experiments indicate that further clinical studies should be done with lower doses of BRL 33 575 or prolonged dosage intervals.

Fibrinogen↗
PubMed1984

[A frequent problem in the laboratory control of heparinization: contamination of blood specimens with exogenous heparin].

If blood for monitoring of heparin therapy is collected through indwelling catheters it may be contaminated by exogenous heparin. A prospective study comparing thrombin times in plasma obtained by venipuncture and by collection through heparin perfused catheters showed that 26 out of 77 catheter samples were contaminated. In 16 of these 26 cases, overestimation of the heparin effect would have led to incorrect dosage recommendations. It is concluded that blood for laboratory monitoring of heparin treatment should be collected by venipuncture.

Blood Coagulation Tests↗
PubMed1983

[Systemic thrombolysis of arterial occlusions of the lower extremities. Comparison of various treatment schedules].

From 1971-1982 121 patients with arterial occlusions of the lower limbs underwent systemic thrombolysis treatment at the Kantonsspital Basel. During 4 time-periods, 3 different treatment schedules were evaluated consecutively: a) individually titrated high dose streptokinase (SK), b) individually titrated low dose SK and c) p-plasmin, followed by low dose SK-infusion. Thrombolytic success rates did not differ significantly with the 3 treatment schedules. Nevertheless, the p-plasmin-SK scheme tended to the thrombolytically more effective (68%) than high-dose (58%) or low-dose (50%) SK. The most frequent side effects were bleeding complications. In 6 out of the 121 patients, intracranial bleeding occurred and was lethal in 1 of the patients. The incidence of this most serious complication of 4/47 during the sequential p-plasmin-SK schedule led the authors to abandon this scheme for the treatment of arterial occlusions. The intracranial bleeding complications are much less frequent in patients with deep venous thrombosis undergoing systemic thrombolysis, and hence seem to be due in part to the generalized arteriopathy often present in patients with arterial occlusions. The p-plasmin-SK schedule induced the strongest systemic proteolysis in the light of thromboplastin time and factor V values. Comparison of these data with those of other authors is very difficult because of differences in patient selection, treatment schedules and observance of contraindications. The serious prognosis for patients with acute arterial occlusions, with an overall hospital mortality of 26% (experience at the Kantonsspital Basel, 1978-1982) relativizes the importance of the side effects due to systemic thrombolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗