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Biomedical subjects

E Knoll

Publications and source records attributed to E Knoll.

At least 37 records · Page 2Linked to original sources

Selective inhibition of angiotensin II-mediated vasoconstriction by lipoxygenase blockade.

We have previously demonstrated that the lipoxygenase (LO) pathway has a specific role in the effect of angiotensin II (ANG II) on aldosterone secretion. To elucidate whether the LO pathway also participates in the vascular effects of ANG II, the nonselective LO inhibitor phenidone (PHE; 30 mg/kg) was administered to rats 1 h before graded dose ANG II infusion. PHE reduced the LO product 12-hydroxyeicosatetraenoic acid (12-HETE) in deendothelialized aortas by an average of 36% as determined by radiometric detection with high-performance liquid chromatography and radioimmunoassay methods. In parallel, the peak systolic pressor response to ANG II was lowered from 36.2 +/- 3.7 to 16.8 +/- 2.0 mmHg. The peak pressor responses to ANG II were also reduced by two other LO inhibitors, baicalein (30 mg/kg) and esculetin (60 mg/kg) (13.9 +/- 2.4 and 22.1 +/- 4.7 mmHg, respectively; P less than 0.01 compared with control rats for both), but not by the cyclooxygenase inhibitor indomethacin. The LO inhibitors baicalein (7.5 X 10(-5) M) and PHE (10(-4) M) markedly attenuated the in vitro contractile response to ANG II of femoral artery rings. In contrast, neither the in vivo nor in vitro constrictor responses to norepinephrine were affected by baicalein. Thus lipoxygenase blockade induces a direct and selective inhibition of ANG II-induced vasoconstriction. The LO pathway may have an important role in mediating the pressor effect of ANG II.

Angiotensin II↗

Plasma free and conjugated catecholamines in clinical disorders.

Plasma free and sulfoconjugated norepinephrine (NE), epinephrine (E) and dopamine (DA) concentrations measured in patients with thrombocytopenia or thrombocytosis, in newborns and pregnant women were not statistically different from values determined in 41 healthy volunteers. The percentage free to total NE, E and DA was 30 +/- 10%, 35 +/- 11% and 1.5 +/- 1.1% (mean +/- SE) in the controls, resp; not different from the previously described patients or from patients with liver failure who showed significantly higher free and conjugated NE and E levels when compared with controls (p less than 0.01, resp.). Conjugated catecholamine (CA) levels from the femoral artery and from multiple sites in the venous system sampled in patients undergoing intracardiac measurements were identical. The data suggest that sulfation of CA may not be simply ascribed to platelets, to the liver, to vascular beds, or to organs along the vena cava including the adrenal glands. The parallel increase of free and conjugated NE with age in healthy controls, as well as the unchanged degree of conjugation in patients with increased spillover of NE and E caused by a pheochromocytoma or by a heart attack, suggest that there is a balance between free and sulfated CA. A normal ratio of free to conjugated NE and E observed in patients receiving high dosage DA infusion further indicates that there is an adequate sulfate supply and no apparent substrate inhibition of the conjugation process. Because the percentage free of total NE, E and DA were significantly lower in patients in the hypothyroid state when compared with controls (p less than 0.01, resp.), hypothyroidism may affect the balance of free to conjugated CA in a yet unknown way.

Adolescent↗

The science of language and the evolution of mind: Max Müller's quarrel with Darwinism.

For Darwinism to succeed as a general theory of the development of life, it had to account for at least the rudiments of all human characteristics. Thus Darwin and his colleague G. J. Romanes had to make "mental evolution" the basis for scientific psychology. F. Max Müller, Oxford's professor of comparative philology, drew on Kant's work, Romantic Naturphilosophie, and his views on the history of language and the relation of language to thought to maintain that language showed a difference not in degree but in kind between man and the lower primates. In his debate with Romanes, he argued that the study of language, not Darwinist natural history, should be the basis for a science of human psychology. However, the two authors had such different definitions of the key terms in their discussion that their differences were not only unresolved but irresolvable.

Animals↗

Determination of catecholamines in plasma by HPLC and amperometric detection. Comparison with a radioenzymatic method.

The determination of norepinephrine and epinephrine in plasma by HPLC with amperometric detection was modified, giving detection limits of 25 ng/l for norepinephrine and epinephrine, respectively, using 1 ml plasma. In order to achieve this sensitivity, it was necessary to minimize the background noise by modification of instrumentation and specimen handling. Particularly important was the extra purification of the reagents, the application of micro-bore HPLC, the enzymatic cleavage of uric acid and temperature control of the amperometric cell and the amplifier. Comparison of the present method with the radioenzymatic determination of catecholamines resulted in coefficients of correlation of r = 0.924 and 0.919 for norepinephrine and epinephrine, resp. (n = 38). The concentrations of the 38 different samples used for the comparison were in the physiological range.

Catecholamines↗

[Routine clinical chemical analysis with prepared reagent carriers].

The determination of glucose, uric acid, urea, triglycerides, cholesterol, sodium, and potassium was investigated using an Ektachem DT 60 and the Ektachem DTE-module. The coefficients of variation ranged from 0.5 to 5.3% for within run and from 1.1 to 4.7% for within day precision. The deviations of the measured values from the assigned values (determined by gas chromatography and mass spectrometry, or by interlaboratory surveys were less than 5%. The determination of urea in control samples was influenced by matrix effects, but not the analysis of patients samples. The comparative analysis of patient samples with routine methods and multilayer reagent carriers showed good agreement. The linear coefficients of correlation ranged from 0.9318 (sodium) to 0.9945 (triglycerides). The analyser is easy to use and has been proved to be very reliable. The throughput of 65 substrate and 15 electrolyte determinations per hour is sufficient for the medical practitioner or small laboratories.

Blood Chemical Analysis↗

[Analytical and technical reliability of the ELT-8 laser hematologic counter].

The ELT-8 laser haematological cell counter is a fully mechanized instrument, which measures the forward scatter of light from a helium-neon laser caused by suspended particles. The apparatus has high practicability, and uses a very small sample volume of 100 microliters. The operational procedure is simple and quickly learned. In the second year of operation, down time for the instrument was, on average, 8 hours/month. Depending on the parameter, the precision of the measurements are between 0.5 and 4% in series, and 1-9% day-to-day. The highest scatter of results was shown for thrombocyte counting, but this may be due to instability of the control samples. There was no carry over between samples containing different concentrations of any of the measured parameters. Lipaemia and haemolysis of samples can lead to false results or false interpretation of results. Cold agglutinins, active against erythrocytes and thrombocytes, can cause significant interference, and this influence can be recognized from discrepancies between the erythrocyte count and haemoglobin concentration or mean corpuscular volume (MCV), and from the presence of thrombopenia in the absence of clinical symptoms (pseudothrombopenia). In such cases a histogram is useful. The stability of 72 blood samples was investigated during storage for 4 days at 4 degrees C. The erythrocyte count was very stable, whereas thrombocyte and leukocyte counts sometimes showed irregular variations. The apparatus gives a linear response up to the following limiting values: leukocytes 85 X 10(9)/l, erythrocytes 8 X 10(12)/l, thrombocytes 10(12)/l, haemoglobin 230 g/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Agglutinins↗

Influence of food intake on concentrations of plasma catecholamines and cortisol.

Plasma concentrations of epinephrine, norepinephrine, dopamine and cortisol were determined in four healthy volunteers--resting completely in bed--before and after food intake. Meals were provided at 17.00 h on the first day and at 12.00 h on the second day of the test. Blood samples were drawn every 15 minutes. Epinephrine, norepinephrine, dopamine, and cortisol showed a clear dependence on food intake. After the meals plasma concentrations of the four analytes showed rises, which were more pronounced after lunch at 12.00 h than after dinner at 17.00 h. An increase of epinephrine was observed shortly before meal-times; this could be caused by physiological adaptation to the usual rhythm of food intake and reflex response to expectation of the meal.

Adult↗

Problems in the development of radioimmunoassay of catecholamines.

This review describes experiments to produce antibodies towards the catecholamines and some catecholamine metabolites with the intention of developing radioimmunological methods. First, attempts to produce antibodies to the catecholamines themselves are described. In the course of synthesis of immunogens of catecholamines, it was necessary to exercise special care - e.g. the introduction of protecting groups - owing to the great susceptibility of the catechol structure to oxidation. Despite many efforts, only one working group (Miwa et al.) has reported in a series of papers the successful production of antibodies to catecholamines, but they did not develop a radioimmunoassay. In contrast, antibodies to some metabolites of the catecholamines - such as 3,4-dimethoxyphenylethylamine, the 3-O-methylated catecholamines (normetanephrine, metaneprine, and 3-methoxytyramine) as well as 3-methoxy-4-hydroxyphenylethyleneglycol - have been produced, whose avidity and specificity were high enough to permit the development of sensitive radioimmunoassays.

Antibody Specificity↗

Plasma free and conjugated catecholamines in diagnosis and localisation of pheochromocytoma.

In six patients urinary excretion of vanillylmandelic acid and catecholamines (CA) could establish the diagnosis of pheochromocytoma. Free norepinephrine (NE) in plasma was within the normal range in two patients and plasma free epinephrine (E) was only marginally elevated in one of them. The degree of CA conjugation was not altered and scattered as in controls and was therefore not complementary to the usual determination of plasma free CA. The intermittent nature of CA secretion by the tumour could be demonstrated by multiple blood samplings during a 48-h study period in two patients, e.g. normal plasma values might be associated with pheochromocytoma if measurements are made during a trough. Thus a single peripheral CA determination cannot be of discriminative value in the diagnosis of pheochromocytoma unless it shows marked elevation. Ten patients subjected to intracardial measurements and five patients suspected of having a pheochromocytoma underwent venous catheterisation to determine their free and conjugated plasma CA. In controls CA values near the orifices of adrenal veins differed enormously and partly overlapped with corresponding levels of patients with pheochromocytoma. In one patient with surgically proven left adrenal tumour highest concentrations of CA were measured in the vena cava superior. These high CA concentrations, caused by paroxysmal release of CA by the tumour arouse suspicion of an additional, ectopic tumour. Because venous catheterisation cannot be relied on implicitly we propose computed tomographic scanning as a first step in localisation of a pheochromocytoma.

Adrenal Gland Neoplasms↗