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Biomedical subjects

S Fischer

Publications and source records attributed to S Fischer.

At least 379 records · Page 21Linked to original sources

The half-lives of IgG subclasses and specific antibodies in patients with primary immunodeficiency who are receiving intravenously administered immunoglobulin.

With the increased use of immunoglobulin for intravenous use (IGIV) as replacement therapy for patients with primary immunodeficiencies, a natural concern is whether such preparations demonstrate a normal turnover rate with regard to total IgG, individual IgG subclasses, and specific antibody titers. We have conducted such a pharmacokinetic study on a cohort of eight patients with an IGIV preparation, Gammagard. For total IgG, the half-life found was 25.8 days; for IgG1 it was 29.7 days; for IgG2 it was 26.9 days; and for IgG3 it was 15.7 days. The results are similar to those reported for endogeneous IgG. Half-lives for antibodies to S. minnesota (Re 595 mutant), cytomegalovirus, and S. pneumoniae were of the same order of magnitude as that for total IgG. We conclude that this IGIV preparation is catabolized in patients with primary immunodeficiency at a rate similar to that of native IgG in normal individuals.

Adolescent↗

[Nucleation time and lithogenic index in obese patients and in patients with cholecystolithiasis].

The gallbladder bile of obese patients without gallstones is supersaturated with cholesterol. The cholesterol saturation index (CSI, LI) of 27 obese patients was 1.32 +/- 0.2. The CSI of 24 normal weight gallstone patients was determined with 1.16 +/- 0.37 and is therefore not significantly different from CSI of obese stone free individuals. The supersaturated bile from obese patients does not accelerated the nucleation of cholesterol crystals. The nucleation time of obese persons was statistically significant longer (16.0 +/- 3.0 days) than in gallstones patients (6.0 +/- 0.78 days) (p less than 0.001). In 50% of the patients with gallstones cholesterol monohydratcrystals were present in the native gallbladder bilde, whereas such crystals are found in only 3.7% of the obese group. Liquid crystals occurred more frequently and in larger number in the bile of the obese patients. The stone forming potency of gallbladder bile can be estimated better by the determination of nucleation time and cholesterol crystals occurrence than by the calculation of the saturation index (CSI).

Adult↗

Effects of a bezafibrate sustained release formulation on plasma lipoproteins in patients with hypercholesterolemia. Importance of timing of tablet intake for efficacy.

The therapeutic effect of a single sustained release tablet of bezafibrate (Cedur retard, 400 mg) in primary hypercholesterolemia type IIa and type IIb was investigated in a placebo-controlled randomised study comparing the efficacy of morning vs. evening intake. The decrease in total cholesterol with the morning intake was 18.5% vs. 16.5% for the evening intake (n.s.). HDL-cholesterol increased more in patients taking bezafibrate retard at morning (29.6% vs. 22.4%, p less than 0.05). Bezafibrate was well tolerated. Animal experiments and precursor studies of cholesterol synthesis in man indicate peak activity of HMG-CoA reductase between 1 a.m. and 3 a.m. The data suggest that with normal eating habits during day time other modes of action of bezafibrate besides HMG-CoA reductase inhibition such as reduction of VLDL-synthesis in the liver and an increased fractional catabolic rate, could contribute to the therapeutic effect.

Alkaline Phosphatase↗

More exercise for the hyperlipidaemic patients?

Epidemiological studies have left no doubt that moderate to vigorous physical training (PT) of endurance type decreases atherogenic lipoprotein fractions and increases vasoprotective lipoproteins. Depending on the underlying metabolic abnormality in various dyslipoproteinaemias a different response to endurance training was observed. PT is particularly effective in most forms of primary hypertriglyceridaemias. PT acts on both excessive VLDL production and fractional catabolic rate of TG--rich lipoproteins. However, improved removal seems to be of dominating importance. In primary hypercholesterolaemia LDL--cholesterol levels did not change during a 4 weeks exercise regimen with standardized isocaloric lipid lowering diet. In observational studies with hyperlipidaemic patients with stable body weight and under lipid lowering diet, during the first 4-6 weeks no significant effect on HDL was seen, whereas longterm studies clearly demonstrate an increase in HDL--cholesterol. Further beneficial effects of PT in hyperlipidaemic patients are improved glucose tolerance, down--regulation of hyperinsulinaemia, lowering of blood pressure and correction of hypercoagulability of the blood.

Arteriosclerosis↗

Loss of fat, water, and protein during very low calorie diets and complete starvation.

The magnitude and composition of weight loss obtained in obese women on two forms of very low calorie protein-supplemented diets (Cambridge diet, Dresden drink) as well as by complete starvation has been investigated. With the VLCD, nitrogen equilibrium was reached on the 10th day of fasting, the cumulative nitrogen balance also being compensated. Nearly half of the body weight loss is due to loss of fat. In order to assess the benefit of fasting regimes, we propose to measure at least two parameters which are independent of each other, e.g., nitrogen balance and total body water. Both types of VLCD were equally effective, safe, and acceptable in achieving rapid body weight reduction.

Adipose Tissue↗

Correlation between phosphorylation and kinase activity of a tyrosine protein kinase: p56lck.

P56lck is the product of a cellular oncogene highly expressed in lymphoid cells. Tyrosine kinase activity was measured by using an exogenous substrate: polyamino acid glutamic acid-tyrosine (4:1) (PGT). Different levels of phosphorylation of p56lck were achieved by the utilisation of SH reagents and different lengths of incubation time. The phosphorylation of PGT was proportional to the level of phosphorylation of p56lck. Identical results were obtained with crude membrane preparations and with p56lck partially purified on immunecomplexes.

Adenosine Triphosphate↗

[Hemoglobinopathies and erythrocyte enzyme deficiencies in Switzerland: laboratory diagnoses of the last 10 years].

In 26,224 blood samples sent to the laboratory in the last 10 years, abnormal haemoglobins were present in 565 samples and 5579 cases of thalassaemia have been diagnosed. With routine testing a red cell enzyme deficiency was found in 722 samples. Laboratory tests for delta beta-thalassaemia, alpha-thalassaemia and glucose-6-phosphate dehydrogenase deficiency had been requested only for a minority of the detected cases. It is obvious that many physicians are not familiar with these disorders.

Erythrocytes↗

The amino terminal region of the p56 lck from LSTRA exerts negative modulation on the tyrosine kinase activity.

High levels of tyrosine kinase activity have been detected in the murine lymphoma LSTRA (p56). The functional domains of this kinase have been studied by the use of antibodies generated against peptides from the amino terminal region and from the tyrosine autophosphorylation site. The amino terminal antibody had higher affinity for the p56 than the antibody directed against the phosphotyrosine site. However, the phosphorylation of exogenous substrate by p56 was lower when the tyrosine kinase was immunocomplexed by the antibody against the amino terminal region than when the kinase was complexed by the phosphorylation site antibody. This suggests that in the N-terminal region exist structures which modulate the tyrosine kinase activity of the p56.

Animals↗

Dietary docosahexaenoic acid is retroconverted in man to eicosapentaenoic acid, which can be quickly transformed to prostaglandin I3.

In a 24 h kinetic study docosahexaenoic acid (DCHA, C22:6n-3) or eicosapentaenoic acid (EPA, C20:5n-3) were given in a single dose to healthy male volunteers. PGI3-M, the main urinary metabolite of prostaglandin I3 was below the detection limit in the control periods, but was excreted already in the first 4 h after ingestion of DCHA or EPA and decreased thereafter. Excretion of PGI2-M did not change significantly. In a second dietary trial DCHA and EPA were given cross-over to 7 healthy male volunteers for 6 days. PGI3-M was formed after DCHA and EPA in amounts of 35 and 20% of PGI2-M and showed a considerable interindividual variation. The structure of PGI3-M was verified by independent biochemical synthesis. Our data indicate that dietary DCHA is retroconverted to EPA in man, which is quickly transformed--like dietary EPA itself--to prostaglandin I3. DCHA may therefore serve as a precursor fatty acid for EPA and its cyclooxygenated and lipoxygenated products.

Animals↗

Alpha-linolenic acid deficiency in man: effect of ethyl linolenate on plasma and erythrocyte fatty acid composition and biosynthesis of prostanoids.

Treatment of human alpha-linolenic acid deficiency (ALAD) with ethyl linolenate is reported. The patient's scaly dermatitis nearly disappeared after 5-d supplementation with 0.1 mL ethyl linolenate. Pretreatment content of various n-3 fatty acids in RBC was 0-15% of healthy controls. After 14 d of supplementation, cholesterol and triglycerides were reduced by 70% of pretreatment values, 22:5n-3 and 22:6n-3 increased three- to fourfold while 18:3n-3 and 20:5n-3 remained low, indicating a rapid elongation and desaturation of 18:3n-3 in ALAD. Urinary excretion of PGI2-M was approximately 10 times higher than in healthy control subjects, while PGI3-M excretion was low. Linolenate supplementation increased PGI2-M excretion twofold, while PGI3-M remained near detection limit. Platelet capacity to synthesize TXA2, and urinary excretion of TXB2+3-M were nearly unaffected by supplementation. The results confirm that the minimal daily requirement of alpha-linolenic acid is 0.2-0.3% of total energy.

Aged↗

Cell-cell interactions in the eicosanoid pathway.

In vitro experiments carried out in several laboratories indicate that cell components of hemostatic plugs, thrombi, and inflammatory lesions are capable of sharing precursors and intermediates of both the lipoxygenase and cyclooxygenase systems. These cells produce new eicosanoids in a stimulus-specific manner. It is therefore important to further elucidate mechanisms by which eicosanoids are formed during cell-cell interactions and the functional implications thereof.

Animals↗

Can automated haematology analysers discriminate thalassaemia from iron deficiency?

The use of automated analysers in population screening for beta-thalassaemia has been a matter of controversy. The new fully automated haematology analyser Sysmex E-5000 (Toa Medical Electronics Co. Ltd) facilitates the discrimination of heterozygous thalassaemia from iron deficiency anaemia. In addition to haemoglobin, mean corpuscular haemoglobin and mean corpuscular volume, the red cell size-distribution width is measured. In patients with hypochromic microcytic red cells, the Sysmex data have been evaluated and compared with the indices described by England and Fraser [Lancet i, pp. 449-452, 1973], Mentzer [Lancet i, p. 882, 1973] and by Shine and Lal [Lancet i, pp. 692-694, 1977]. For the detection of beta-thalassaemia trait, the size-distribution width is superior to the previously described indices. The sensitivity is 79%, the specificity 95% and the predictive value for a positive test 94%.

Diagnosis, Differential↗

The cholinergic system in aging.

A morphometric analysis of neuronal loss during normal aging was performed in the nucleus basalis Meynert complex of the basal forebrain (Nbm) (nucleus septi medialis, nucleus of Broca's diagonal band, nucleus basalis) and the ciliary ganglion, a peripheral cholinergic structure, in patients free of neurological and psychiatric illness. As a basis for morphometric evaluation of the Nbm complex, a three-dimensional reconstruction of this complex structure was made. Neuronal counts in the Nbm complex and the ciliary ganglion remained stable up to the age of 60 or 50 years, respectively. After this age the number of neurons declined moderately in ciliary ganglion in all cases studied as well as in the Nbm complex in some cases (-20 and -25%, respectively, at about 90 years of age). In 3 out of 8 cases older than 60 years, neuronal counts in the Nbm complex were not reduced, so that no significant decline in neuronal number is apparent from the mean values of the 17 cases studied. No age-related changes were found in the neuronal distribution amongst the different subgroups of Nbm neurons using the alternative nomenclature of Mesulam et al. [J. comp. Neurol. 214: 170-197, 1983]. Our results provide no evidence that the cortical cholinergic projection system and peripheral cholinergic neurons might be especially vulnerable during normal aging. The severe degeneration of the cholinergic cortical projection system in SDAT is probably caused by mechanisms different from those acting during normal aging.

Adult↗

Nonexocytotic release of endogenous noradrenaline in the ischemic and anoxic rat heart: mechanism and metabolic requirements.

The release of endogenous noradrenaline and its deaminated metabolite dihydroxyphenylglycol in the myocardium have been studied in the isolated perfused heart of the rat subjected to three models of energy depletion: ischemia, anoxia, and cyanide intoxication. Anoxia and cyanide intoxication were combined with substrate deficiency at constant perfusion flow. All three energy-depleting procedures caused a similar overflow of noradrenaline which, following a constant delay of 10 minutes without increased release, amounted to more than 25% of total heart content within 40 minutes. This noradrenaline overflow was not diminished in the absence of extracellular calcium and was inhibited by the uptake1 blocker desipramine in all three experimental models, indicating a common and nonexocytotic release mechanism. In the presence of glucose, neither anoxia nor cyanide intoxication resulted in a measurable noradrenaline overflow. Conversely, blockade of glycolysis or glucose depletion prior to ischemia or cyanide poisoning accelerated the noradrenaline overflow, demonstrating a key role of the sympathetic nerve cells' energy status in causing nonexocytotic catecholamine release. Blockade of energy metabolism in the presence of oxygen (cyanide model) resulted in the overflow of high amounts of dihydroxyphenylglycol that was not inhibited by uptake1 blockade. The release of the lipophilic dihydroxyphenylglycol by diffusion reflects deamination of axoplasmic noradrenaline by monoamine oxidase. Since saturation of the enzyme could be excluded in this model dihydroxyphenylglycol release can be taken as a mirror of cytoplasmic noradrenaline concentration. The results obtained by these studies indicate that nonexocytotic catecholamine release is a two-step process induced by energy deficiency in the sympathetic varicosity. In a first step, noradrenaline is lost from storage vesicles, resulting in increasing axoplasmic concentrations. The second step is the rate-limiting transport of intracellular noradrenaline across the cell membrane by the uptake1 carrier that has reversed its normal net transport direction.

Animals↗

Sympathetic modulation of the pressure-dependent renin release in conscious dogs.

The relationship between mean renal artery pressure and renal venous-arterial plasma renin activity-difference (renin stimulus-response curve; RSRC) was studied in 15 conscious dogs by a stepwise reduction of renal artery pressure down to the lower limit of renal blood flow (RBF)-autoregulation. The RSRC has a flat section above threshold and a steep slope - indicating a 100% increase of renin release per 2.5 mmHg - below a well defined threshold pressure (Pth). Pth may remain unchanged for 4 weeks. A reflex activation of the renal sympathetic nerves by common carotid occlusion increased Pth by 16.5 +/- 3.2 mmHg (P less than 0.01); this effect was abolished by intrarenal alpha-blockade (prazosin). A low dose intrarenal infusion of methoxamine, which did not change RBF, increased Pth by 8.5 +/- 0.7 mmHg (P less than 0.001). We conclude that in the resting conscious dog renal perfusion pressure is a powerful factor in the control of renin release. The renal sympathetic nerves modulate the pressure-dependent mechanism within the autoregulatory range of renal blood flow by an alpha-adrenergic adjustment of threshold pressure.

Animals↗