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Biomedical subjects

E Schulze

Publications and source records attributed to E Schulze.

At least 109 records · Page 6Linked to original sources
PubMed1986

Sites of microtubule assembly and disassembly in the mitotic spindle.

We have microinjected biotinylated tubulin into mitotic fibroblast cells to identify the sites in the spindle at which new subunits are incorporated into microtubules (MTs). Labeled subunits were visualized in the electron microscope using an antibody to biotin followed by a secondary antibody coupled to colloidal gold. Astral MTs incorporate labeled subunits very rapidly by elongation of existing MTs and by new nucleation from the centrosome. At a slower rate, kinetochore MTs incorporate subunits at the kinetochore progressively during metaphase, suggesting a slow poleward flux of subunits in the kinetochore fiber. When cells injected in metaphase were examined in anaphase, a significant fraction of kinetochore MTs was unlabeled, suggesting that depolymerization had occurred at the kinetochore concomitant with chromosome to pole movement. The existence of opposite fluxes at the kinetochore during metaphase and anaphase suggests that two separate forces are responsible for chromosome congression and anaphase movement.

Anaphase↗
PubMed1986

Antagonistic effects of bisoprolol on several beta-adrenoceptor-mediated actions in anaesthetized cats.

The beta-adrenoceptor antagonistic activity of i.v. administered bisoprolol ((+/-)-1-[4-(2-isopropoxyethoxymethyl)-phenoxy] -3-isopropylamino-2-propanol, hemifumarate) was studied under two different sets of experimental conditions in anaesthetized cats and compared to the activity of atenolol and propranolol. The responses of several target organs to beta 2-adrenoceptor stimulation were used: inhibition of isoprenaline effects on diastolic blood pressure, hindlimb perfusion pressure, soleus muscle contractility and histamine aerosol-induced bronchoconstriction. The inhibition of isoprenaline-induced tachycardia served as indicator of beta 1-antagonism. The slopes of agonist dose ratio vs. antagonist dose effect were close to unity for propranolol but deviated from unity for atenolol and even more so for bisoprolol. In spite of the ensuing difficulty of comparisons, bisoprolol showed the most pronounced selectivity indices (10-20), followed by atenolol (1-7.5) and propranolol (0.3-1.6). Thus, bisoprolol exhibited a higher degree of beta 1-selectivity in the cat than did atenolol, regardless of the parameter used for measurement of beta 2-antagonism. Propranolol proved to be non-selective or even had a somewhat higher affinity for beta 2- than for beta 1-adrenoceptors.

Anesthesia↗
PubMed1986

Pharmacological profile of tazasubrate, a new cholesterol-lowering agent.

The properties of tazasubrate (2-phenyl-2-[(6-ethoxy-2-benzothiazolyl)thio]propionic acid), a potent hypocholesterolemic agent, were studied in rats. Tazasubrate was found to be a reliable and highly effective hypocholesterolemic agent. There was a marked and reproducible reduction of serum cholesterol in various rat models differing in age, sex and diet, an improvement of the pathological lipoprotein pattern, slight but variable effects on serum triglycerides and phospholipids, no accumulation of intermediates of cholesterol biosynthesis, no inhibition of phospholipid metabolism (i.e. no induction of phospholipidosis), no interaction with the thyroid gland, and in contrast to fibrates, only minimal induction of peroxisomes in hepatocytes.

Animals↗
PubMed1986

Microtubule dynamics in interphase cells.

The sites of microtubule growth and the kinetics of elongation have been studied in vivo by microinjection of biotin-labeled tubulin and subsequent visualization with immunocytochemical probes. Immunofluorescence and immunoelectron microscopy demonstrate that injected biotin-labeled subunits are incorporated into new segments of growth which are contiguous with unlabeled microtubules. Rapid incorporation occurs by elongation of existing microtubules and new nucleation off the centrosome. The growth rate is 3.6 micron/min and is independent of the concentration of injected labeled tubulin. This rate of incorporation together with turnover of existing microtubules leads to approximately 80% exchange in 15 min. The observed kinetics and pattern of microtubule turnover allow for an evaluation of the relevance of several in vitro models for steady-state dynamics to the in vivo situation. We have also observed a substantial population of quasi-stable microtubules that does not exchange subunits as rapidly as the majority of microtubules and may have specialized functions in the cell.

Animals↗
PubMed1986

High beta 1-selectivity and favourable pharmacokinetics as the outstanding properties of bisoprolol.

Bisoprolol, (+/-)1-(4-[(2-isopropoxyethoxy)-methyl]-phenoxy)-3-isopropyl-amino -2- propanol-hemifumarate, is a new, highly selective beta 1-adrenoceptor blocking agent without intrinsic sympathomimetic activity and low to moderate local anaesthetic activity. As demonstrated in binding experiments, and in classical pharmacological studies using rats, guinea pigs, cats, and dogs, bisoprolol markedly differentiated between beta 1-adrenoceptors of the heart, or the renal juxtaglomerular apparatus, and the beta 2-subtype in arterial blood vessels, bronchi, liver, or skeletal muscle. Up to concentrations nearly 100-fold higher than the therapeutic plasma levels in humans, bisoprolol did not affect the functional refractory period of the heart, and was devoid of a direct suppressive effect on myocardial contractility and of calcium antagonistic properties in heart and vascular muscle. The pattern of haemodynamic effects of bisoprolol was typical of beta-blockers and included decreases in blood pressure (BP), heart rate (HR), and cardiac output, concomitant with an increase in calculated total peripheral resistance. In contrast to other beta-blockers, bisoprolol increased renal blood flow in anaesthetized dogs. Bisoprolol lowered BP in hypertensive dogs and rats, attenuated the development of spontaneous hypertension in rats, decreased plasma renin activity and protected the heart from the sequelae of transient ischemia. It did not block presynaptic beta-adrenoceptors in blood vessels. Serum lipids and the serum lipoprotein profile remained unaltered after bisoprolol. Bisoprolol was devoid of affinity for autonomic receptors other than beta-adrenoceptors or for autacoid receptors. This is probably one of the reasons why bisoprolol did not affect the function of the central nervous, respiratory, and gastrointestinal systems in an obvious way. The high beta 1-selectivity of bisoprolol is linked with extremely favourable pharmacokinetic properties. These include nearly complete enteral absorption and virtual absence of liver first-pass metabolism, both resulting in high bioavailability, long plasma half-life, pharmacokinetics that are linear over a wide dose range and independent of age, food intake and hydroxylator status, low plasma protein binding, and a 1:1 ratio of hepatic metabolization to renal elimination of the unaltered substance. This sum of favourable pharmacological and pharmacokinetic properties characterize bisoprolol as an optimized beta-blocker.

Adrenergic beta-Antagonists↗
PubMed1986

Morphogenesis and the control of microtubule dynamics in cells.

Microtubules show unusual dynamic properties at steady state in vitro. While overall the polymer mass remains stable, individual polymers in the population are either growing or shrinking. This phenomenon called dynamic instability is best explained by the known coupling of polymerization to GTP hydrolysis, and the hypothesis that the stability or instability of the whole polymer is determined by whether GTP or GDP is bound to the terminal subunit. Similar unusual dynamics have now also been found in vivo. By visualizing new subunit assembly after injection of tubulin modified with biotin into living fibroblast cells, we can visualize new growth on individual microtubules with antibody to biotin. Microtubules grow in vivo at about 4 microns min-1 and after rapid and precessive depolymerization old microtubules are replaced by new growth from the centrosome. Some microtubules turn over much more slowly and these stable microtubules have a different spatial distribution from the majority of dynamic ones. The existence of both stable and dynamic microtubules in the same cell suggests a model for morphogenesis of the microtubule cytoskeleton. The rapid turnover of microtubules in the cell provides a complex population upon which selective factors can act. Stability can be generated at the end of the polymer and affects the entire microtubule. This model of selective stabilization at the microtubule ends is discussed in terms of recent experiments on the establishment of kinetochore-pole microtubules during mitosis.

Animals↗
PubMed1986

An improved method for adrenalectomy of suckling rats. The influence of thrombin treatment and deoxycorticosterone substitution on survival and on hepatic and renal enzyme activities.

Adrenalectomy of suckling rats is complicated by a high mortality rate, caused by the loss of blood (early mortality) and by the disturbed sodium-potassium balance (late mortality). Treatment of the abdominal cavity with a thrombin solution and a daily administration of deoxycorticosterone glucoside (DOC) decrease the total mortality remarkably. DOC treatment has no influence on renal beta-glucosidase and beta-galactosidase as well as on hepatic tyrosine aminotransferase activity, whereas hepatic serine dehydratase activity exhibits a time- and dosage-dependent response to this hormone. The DOC effect is very likely a consequence of the glucocorticoid-like action of the synthetic hormone, which competes with the endogenous glucocorticoids for the hepatic receptor molecules.

Adrenal Glands↗
PubMed1986

Developmental changes of glycosidase activities in rat renal cortex.

The activities of beta-glucosidase as well as of alpha- and beta-galactosidase increase in the renal cortex of the rat during the early postnatal development. However, while the two galactosidases reach adult values around the end of the second week of life, beta-glucosidase activity exhibits a second steep increase after the third post-uterine week. This rise in activity correlates with the functional maturation of kidney and is confined nearly exclusively to the cytosolic isozyme. The effects of taurocholate, Triton X-100, and dexamethasone on beta-glucosidase isozymes were studied. The results suggest that taurocholate should be included in the assay medium for the measurement of the beta-glucocerebrosidase activity in the diagnosis of Gaucher's disease. For the determination of the total beta-glucosidase activity in samples containing mainly the lysosomal isozyme (perinatal kidney, isolated lysosomes) the use of Triton X-100 is recommended.

Aging↗
PubMed1985

[Effect of calcium antagonists (nifedipine) on nephrocalcinosis and calcium excretion in the rat].

An animal model was established to test the effect of a calcium antagonist on nephrocalcinosis, which was induced by an atherogenous diet, and its effect on the excretion of calcium and other parameters relevant for stone formation. With the administration of nifedipine (Adalat), the grade of nephrocalcinosis could be significantly reduced. Furthermore, with nifedipine the excretion of calcium and sodium in the urine was raised, while phosphate and potassium levels were lowered. The excretion of magnesium and citrate, reduced by an atherogenous diet, could be raised significantly with the administration of nifedipine. The pathophysiological mechanisms underlying the effect of nifedipine on nephrocalcinosis and on the excretion of the urine parameters are discussed. Apparently hypercalciuria is the result of a reduced reabsorption of calcium in the tubulus. The inhibitory effect on the genesis of nephrocalcinosis is possibly due to the lower calcium influx into the tubular cells.

Animals↗
PubMed1984

[Course studies in patients with cytologically inconspicuous, decreasingly accumulating struma nodes].

In 100 patients with inconspicuous findings of a thin-needle puncture of the thyroid gland after 2 years a clinical and cytological after-examination was performed. All test persons were primarily recommended a treatment with thyroid hormone. During the control in no case references to malignant process of the thyroid gland were the result, so that the puncture cytology also retrospectively showed a high exactness. Meanwhile 16 test persons had been strumectomized, in which cases the present histological findings always showed only regressive changes. The clinical after-examination confirmed former results so that also in decreasingly and not accumulating struma nodes a conservative approach is not promising a success. In 12 patients by application of hormones of the thyroid gland the struma had completely receded.

Biopsy, Needle↗
PubMed1984

[Incidence of diabetic retinopathy in diabetic manifestation up to the 30th year of life].

Epidemiological studies of retinopathy on the basis of a relatively closed population of the inhabitants of the county of Neubrandenburg. Of the 521 diabetics with manifestational age of diabetes mellitus till the age of 30 years 415 patients were examined (transverse analysis). 34.5% of them had got a diabetic retinopathy. In our county the juvenile diabetes (average age less than or equal to 30 years) appears with a frequency of 0.114% among the population. Nearly 40% of this group of patients fell ill already before the 15th year of age. 70.6% of the patients with retinopathy suffered from a R I, 24.5% from a R II and 4.9% from a R III.

Adolescent↗
PubMed1983

[Risk of leukemia in aplastic anemias].

Nowadays an increased risk of leucaemia in patients with aplastic anaemias (insufficiency of the bone marrow) is regarded as certain. If the literature of the last 10 years is analysed, the data concerning a leucaemic transformation amount to values between 0 and 16%. Among our clinical material of 108 patients, 38 of them living, 10 patients (correspondingly 9%) showed a leukaemic transformation. The temporary latency between diagnosing of the aplastic syndrome and the leucaemic transformation was maximally 20 years. By cytomorphological investigations, particularly of the judgment of anomalies of erythroblasts, no certain prognosis concerning a possible development of leucaemia. Also cultivation methods of myelopoietic stem cells by means of diffusion chamber and agar culture technique do not seem to allow a certain evidence on prognosis.

Anemia, Aplastic↗