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Biomedical subjects

C Becker

Publications and source records attributed to C Becker.

At least 145 records · Page 8Linked to original sources
PubMed1987

Differential effects of various secretagogues on quantal transmitter release from mouse motor nerve terminals treated with botulinum A and tetanus toxin.

Electrophysiological and electron microscopic techniques were used to investigate the actions of potassium depolarization, black widow venom (BWSV), Ca2+-ionophore A 23187 and hyperosmotic solution on mouse hemidiaphragms poisoned in vitro with botulinum A toxin (BoTx) and tetanus toxin (TeTx). These neurotoxins reduced the frequency of miniature endplate potentials (m.e.p.ps) from 5/s of the control to 2/min and 21/min, respectively. High potassium (25 mmol/l) increased the m.e.p.p.-frequency at BoTx- and TeTx-poisoned endplates to 30/min and 50/s, respectively. The ultrastructure of endplates showed no obvious changes. BWSV (0.04 glands/ml) was just as effective in promoting transmitter release from BoTx-treated endplates as in control preparations. Electron micrographs revealed depletion of vesicles as well as swollen and disrupted mitochondria. When preparations were pretreated with TeTx, BWSV only moderately increased transmitter release and no alterations of the ultrastructure could be observed. At TeTx- or BoTx-poisoned endplates Ca2+-ionophore A 23187 usually produced an extreme reduction of m.e.p.p.-frequency (0.005/s), sometimes preceded by a short burst-like release. The ultrastructure of these endplates was not obviously affected. Application of hyperosmotic solution to BoTx- or TeTx-poisoned preparations further reduced the already low m.e.p.p.-frequency. These results further demonstrate that TeTx and BoTx act at different sites in the transmitter releasing process.

Animals↗
PubMed1987

Pericardial effusion causes interstitial pulmonary edema in dogs.

The pulmonary effects of pericardial effusion were studied in eight anesthetized dogs, with emphasis on lung mechanics, O2 exchange, and extravascular thermal lung volume (ETV) accumulation, while warm saline was instilled into the pericardium to elevate pericardial pressure. The results were compared with those from four time-controlled and sham-operated dogs. ETV, as measured by a double-indicator technique, increased from 8.1 +/- 0.8 ml/kg at a pericardial pressure of 0 mm Hg to 12.9 +/- 2.1 ml/kg at 11.0 mm Hg (p less than .01). In the control group, ETV increased from 6.5 +/- 0.7 to 8.2 +/- 0.5 ml/kg over an equal time span. This increase in ETV in the experimental dogs was inversely related to pulmonary compliance, which decreased by 29% as ETV increased (p less than .05), whereas in the time-controlled group of animals it decreased by 8.8%. Arterial PO2 did not deteriorate during the protocol in either group. Histologic examination showed increased interstitial fluid, but neither alveolar fluid nor septal edema, and gravimetric measurements of lung liquid were also consistent with interstitial fluid accumulation in experimental but not control animals. These findings are concordant with the clinical observation that alveolar edema is rarely seen in the presence of pericardial tamponade. Conceivably, progression from interstitial to alveolar edema did not occur both because of the low pulmonary blood flow that occurs as part of pericardial tamponade physiology and/or because the hydrostatic pressures were not elevated enough to produce higher rates of fluid transudation.

Animals↗
PubMed1987

Voltage-dependent cooperative interactions of calcium channel ligands in intact cardiac cells.

Voltage-dependent Ca channels were studied in living, tissue cultured rat heart cells using patch clamp analysis of single channels and radioligand binding studies at different membrane potentials. Ca channel activating and blocking dihydropyridines (DHP) show cooperative interaction and, therefore, bind to at least two different binding sites on the channel protein. Cooperative interactions between activating and blocking DHP, between DHP and verapamil and between DHP and diltiazem are all voltage dependent. The type of interaction in polarized cells and hence, the possible effects in vivo cannot be predicted from studies in cell homogenates.

Allosteric Site↗
PubMed1986

Acute effects of routine firefighting on lung function.

We undertook a study to determine the acute effects of routine firefighting on lung function and the relationship between these acute effects and nonspecific airway responsiveness. For 29 firefighters from a single fire station, we calculated the concentration of methacholine aerosol that caused a 100% increase in specific airway resistance (Pc100). Over an 8-week period we than measured FEV1 and FVC in each firefighter before and after each 24-hr workshift and after every fire. From 199 individual workshifts without fires, we calculated the mean +/- 2 SD across-workshift change in FEV1 and FVC for each firefighter. Eighteen of 76 measurements obtained within 2 hr after a fire (24%) showed a greater than 2 SD fall in FEV1 and/or FVC compared to two of 199 obtained after routine workshifts without fires (1%; p less than .001). On 13 of 18 occasions when spirometry decreased significantly, we obtained repeat spirometry (postshift) 3-18.5 hr after fires, and on four of these occasions FEV1 and/or FVC were still more than 2 SD below baseline. Decrements in spirometry occurred as often in firefighters with high Pc100s as in those with low Pc100s. In two firefighters in whom FEV1 and FVC fell by more than 10% after fires, we repeated measurements of methacholine sensitivity, and it was increased over the prestudy baseline. These findings suggest that routine firefighting is associated with a high incidence of acute decrements in lung function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Clavines as antitumor agents, 3: Cytostatic activity and structure/activity relationships of 1-alkyl agroclavines and 6-alkyl 6-noragroclavines.

The cytostatic potential of twenty antibiotic agroclavines has been examined in the L5178y mouse lymphoma cell system. Twelve of these compounds are described for the first time. It is shown that the substituent at N-1 of agroclavine is very important whereas the substituent at N-6 is of less influence if it is not hydrogen. Incorporation studies in the presence of 1-propylagroclavine suggest that DNA synthesis in the lymphoma cells is inhibited. The effect on the corresponding [3H]thymidine incorporation in murine spleen lymphocytes is comparably low. Neither a significant change of mRNA efflux nor of DNA polymerase alpha and beta activities was caused. The mechanism of action seems to be a fundamentally new one for ergoline compounds as interactions with alpha-adrenoceptors, dopamine and 5-hydroxytryptamine receptors are not involved.

Animals↗
PubMed1986

Studies on Ca channels in intact cardiac cells: voltage-dependent effects and cooperative interactions of dihydropyridine enantiomers.

We have investigated the effects of two oppositely acting enantiomers of the 1,4-dihydropyridine derivative 202-791 on voltage-dependent Ca channels by combining electrophysiological techniques and binding studies. The (S)-enantiomer of 202-791 promoting prolonged openings of single Ca channels, and thereby increasing transmembrane Ba currents, was classified as channel activator. The (R)-enantiomer favoring a closed state of the channel, and thereby reducing Ba currents, was classified as a channel blocker. Both compounds shifted the steady state current inactivation curve toward more negative potentials. At holding potentials positive to -20 mV, the Ca channel-activating effect of the (S)-enantiomer turned over into a blocking effect. In cells with normal resting potential the combination of the two enantiomers revealed a possible positive cooperative effect resulting in an enhancement of the open state probability of the channels. At depolarized holding potentials the activator enhanced the inhibitory effect of the blocker. Binding studies in intact cells were performed by using the radiolabeled channel-blocking dihydropyridine 3H-(+)-PN 200-110. The results showed a strong increase in binding affinity but no change in binding capacity when the cells were depolarized. Analysis of the interactions of (S)- and (R)-202-791 with this radioligand indicated stimulation of 3H-(+)-PN 200-110 binding by the (S)-enantiomer in polarized cells (membrane potential -38 +/- 4 mV). This effect could be attributed to an increase in binding affinity. The (R)-enantiomer had no such positive cooperative effect, but acted as a purely competitive ligand. Depolarization to 0 mV increased the apparent affinity of both enantiomers by factors of 38 (blocker) and 12 (activator), but abolished the cooperative effect of (S)-202-791 on the binding of the radioligand. Ca ions had little effect on the binding of 3H-(+)-PN 200-110 in polarized cells. However, in the presence of the activating (S)-enantiomer, Ca transformed the usual hyperbolic binding isotherm of the radioligand into a strongly sigmoid curve. Sigmoidicity was minimal with 3-5 microM Ca and maximal with 0.5 mM Ca. Together these data demonstrate homotropic and heterotropic cooperative interactions between channel activator and channel blocker. They indicate that at least two high affinity binding sites for dihydropyridines are associated with voltage-dependent Ca channels. Voltage dependence of both--binding affinity and cooperativity--suggests that these binding sites are located close to a structural component of the channel which is involved in the potential-sensitive gating process.

Aging↗
PubMed1985

Avarol, a cytostatically active compound from the marine sponge Dysidea avara.

A main metabolic product of the sponge Dysidea avara was isolated and purified and subsequently identified as avarol by applying a series of analytical techniques, e.g. [13C]NMR, [1H]NMR and i.r. spectroscopy. This sesquiterpenoid hydroquinone was found to possess strong cytostatic activity. Using the L5178y mouse lymphoma cell system in vitro (roller tube assays) avarol reduced cell growth to 50% at a concentration of 0.9 microM. Avarol treated cells did not show "unbalanced growth". Avarol interfered with mitotic processes, preventing telophase formation. Incorporation studies with precursors for DNA, RNA, protein and glycoprotein syntheses revealed increased incorporation rates in response to avarol treatment. From these results and further autoradiographical experiments it is suggested that inhibition of cell growth is due to changes of the intracellular pools and/or alterations of the permeability properties of the cell membrane for the precursors. Avarol diacetate caused the same cytostatic effect as avarol.

Animals↗
PubMed1985

[Peripheral nerve repair: value of biological glues and epiperineural suture in late interventions. Experimental study in rats].

In order to approximate as close as possible genuine clinical conditions, the sciatic nerve of the rat was divided and then repaired after a delay of one or seven days either by application of a biological glue or by an epiperineural suture technique. The metabolic activity of the sciatic nerve Schwann cells - whether located in the distal or the proximal ends - and that of the (fast acting) white gastrocnemius and (slow acting) red soleus muscle were assessed using 32P-radiolabeled acid-soluble phosphates. Delayed repair, as judged by our biochemical criteria, was equivalent whatever method, biological glue or suture, was used. The frozen and lyophilized forms of the biological glue provided similar results.

Animals↗
PubMed1985

In vitro combination-effect of temocillin with ticarcillin and aminoglycosides on gram-negative and gram-positive bacteria.

The in vitro efficacy of temocillin in combination with ticarcillin and with gentamicin, tobramycin, amikacin and netilmicin against 80 Gram-negative and 20 Gram-positive bacterial strains was compared by use of the checkerboard agar dilution technique. No synergistic or additive effect was seen on the Gram-positive strains. Great variations occurred between the different bacterial species, and the temocillin-ticarcillin combination had only little effect against the Pseudomonas strains tested. On average, only 12% of all strains tested were inhibited synergistically by temocillin-gentamicin combinations, and only 7 to 10% by combinations of temocillin with the other aminoglycosides. However, 25% of Gram-negative strains were inhibited synergistically and 40% of Gram-negative strains were inhibited additively by the combination of temocillin-gentamicin.

Aminoglycosides↗
PubMed1985

Commentary on 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD).

There is deep concern about the long term health effects of exposure to phenoxy herbicides and the contaminant TCDD; however, there is considerable scientific and medical uncertainty regarding the health effects from exposure to these chemicals. There are at least ten ongoing studies on reproduction, morbidity and mortality as well as studies of tissue concentrations of TCDD that are attempting to determine the health effects of these chemicals (see Table 2). Appropriate efforts should be made to prevent human and environmental exposure and to decontaminate the environment while awaiting the results of these investigations. Animal toxicity studies show such wide variations that extrapolations from a different species to humans are tenuous. Human studies on exposed workers and nonoccupational exposures are difficult to interpret because the exposure has not been quantified and because workers were exposed to mixtures of chemicals. Chloracne appears to be an important specific clinical marker of TCDD exposure, however, it can be caused by structurally similar compounds. Many of the past studies on human health effects of 2,4,5-T and TCDD are controversial. Since the scientific data are not firm, no specific statements can be made regarding the long term health effects at this time. Any individual who has had a significant exposure to TCDD should see his/her physician and have appropriate consultation. Long term follow up will be required. Physicians should be instructed regarding the possible manifestations of TCDD exposure to look for chloracne, soft tissue masses, muscle pain, fatigue, peripheral neuropathy, tender hepatic enlargement, enlargement, elevated liver enzymes, elevated lipids, prolonged prothrombin time, hemorrhagic cystitis and hirsutism.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Inhibition of mitosis by avarol, a natural product isolated from the sponge Dysidea avara.

Avarol, a sesquiterpenoid hydroquinone, is a cytostatic agent, isolated from the sponge Dysidea avara. Autoradiographic studies show that in vivo (L5178y mouse lymphoma cells) avarol changes the labelling index in favour of the fraction of unlabelled cells (from 1.24 to 1.04). At concentrations below the 50% inhibition dose, the mitotic index increases from 6.5 +/- 0.5 to 10.4 +/- 0.8; at higher concentrations the formation of mitotic figures is almost completely suppressed. In vitro studies applying the methods of viscosimetry and electron microscopy demonstrate that avarol inhibits assembly of brain microtubule protein at an at least stoichiometric concentration ratio. Moreover, evidence is presented that the new antimitotic agent avarol inhibits protofilament elongation rather than lateral association of tubulin during protofilament formation. The results suggest that avarol interferes with polymerization of tubulin both in interphase and during mitosis.

Animals↗