Search PubMedSearch

Biomedical subjects

C Becker

Publications and source records attributed to C Becker.

At least 163 records · Page 9Linked to original sources

Recovery of beta-adrenoceptors and cyclic AMP response after long term treatment of intact heart cells with beta-blockers.

We have studied the recovery of receptor binding and of isoprenaline-stimulated cyclic AMP responses after chronic (2-5 days) exposure of tissue-cultured living rat heart cells to several beta-adrenoceptor antagonists. Most experiments were performed with [3H]- (+/-)-carazolol and [3H]-(+/-)-CGP 12177, as prototypes of high affinity lipophilic and hydrophilic ligands respectively. Chronic antagonist treatment did not alter the total number of receptors nor did it cause intracellular accumulation of the ligands. At the end of the treatment, radiolabelled antagonists were displaced either by 'infinite' dilution of the incubation medium or by competitive displacement with the non-labelled ligand (-)-timolol. In dilution assays dissociation of carazolol from specific sites was biphasic with t 1/2 values of 41 +/- 14 and 219 +/- 15 min. Dissociation of CGP 12177 was monophasic with t 1/2 of 102 +/- 2 min. Timolol enhanced the dissociation rates of both radioligands and suppressed the slow phase of carazolol dissociation. Isoprenaline-stimulated cyclic AMP formation did not recover in parallel with the release of the two antagonists from receptor binding sites. To reach about 80% of control values for receptor availability or cyclic AMP response required 3 h and 24 h washout periods, respectively, after carazolol (0.2 nM) treatment, or 1.5 and 12 h washout periods after CGP 12177 (4 nM) treatment. Such a 'decoupling' effect was not observed during recovery from chronic exposure to the antagonists, timolol and propranolol. We conclude that some antagonists cause a novel form of desensitization that is not linked to their partial agonistic potency. Moreover, carazolol-type drugs seem to induce an additional isomeric form of the beta-receptor that is not recognized by other antagonists. These observations could explain the well known discrepancy between long duration of action and rapid removal from the circulation of several antagonists in current therapeutic use.

Adrenergic beta-Antagonists

In vitro combination effects of cefotetan with four aminoglycosides, piperacillin and mezlocillin on gram-positive and gram-negative nosocomial bacteria.

The in vitro efficacy of cefotetan in combination with gentamicin, tobramycin, amikacin, netilmicin against Staphylococcus aureus, Staphylococcus epidermidis and Enterobacter cloacae and with piperacillin and mezlocillin against Escherichia coli, Klebsiella pneumoniae, Serratia marcescens and Enterobacter cloacae was compared by use of the checkerboard agar dilution technique. On average, 60% of the gram-negative and 46% of the gram-positive strains were inhibited by additive, but only 22% of the gram-negative and 2% of the gram-positive bacteria were inhibited by synergistic cefotetan-aminoglycoside combinations. Netilmicin combinations were least active. On gram-negative bacteria, 63% of the cefotetan-penicillin combinations were additive and 11% synergistic. No antagonism occurred with any of the combinations.

Aminoglycosides

The relationship of airways responsiveness to cold air, cigarette smoking, and atopy to respiratory symptoms and pulmonary function in adults.

The response to eucapnic hyperventilation with subfreezing air was studied in a population based sample of 171 adults, all of whom also completed a respiratory questionnaire, spirometry, and skin testing. A positive response to the cold air challenge was defined as [initial FEV1-post-challenge FEV1)/initial FVC) X 100) greater than or equal to 9%. Cigarette smoking was with a positive cold air response: 12 of 128 current and ex-smokers (9.4%) versus 1 of 43 nonsmokers (2.3%) (p = 0.095). Among current and ex-smokers, a positive response to the cold air challenge was significantly associated with asthma (p = 0.046). Using a logistic regression model, both current smoking and response to cold air were significant predictors of the presence of "persistent wheeze" or asthma. A positive skin test to any of the 4 environmental antigens used (ragweed, housedust, trees, and grasses) was significantly associated with cigarette smoking (p = 0.018) and hay fever (p = 0.003 among current and ex-smokers) but not with wheezing or asthma. Though not statistically significant, cold air responders had a lower percentage of positive skin test reactivity than nonreactors. The findings of this cross-sectional analysis suggest that in adults, both airways responsiveness and cigarette smoking are important predictors of wheezing and asthma. Furthermore, the data suggest that airway hyperresponsiveness and atopy are independent traits. However, in adults, these traits are associated with cigarette smoking, a common environmental exposure.

Child

Action of botulinum A toxin and tetanus toxin on synaptic transmission.

Intracellular recordings of the spontaneous activity from mammalian spinal cord neurons in culture demonstrated different sensitivities of excitatory and inhibitory synaptic transmission for the action of tetanus toxin (Tetx) and botulinum toxin type A (Botx). The effects of Tetx and Botx on spontaneous and nerve-evoked transmitter release were compared under identical experimental conditions in experiments on in vitro poisoned mouse diaphragms. At 37 degrees C completely paralyzed endplates are characterized by a very low frequency of spontaneous miniature endplate potentials (m.e.p.p.s) and by a 100% failure to evoke endplate potentials (e.p.p.s) in response to single nerve stimuli. Striking differences in the action of both toxins have been observed when the very low transmitter release probabilities of paralyzed nerve-muscle preparations were increased by tetanic nerve stimulation and/or application of potent K+-channel blockers and/or by reduction of temperature to 25 degrees C. While Botx did not change the short latency between nerve impulse and postsynaptic response, Tetx produced a temporal dispersion of the quantal release suggesting that the toxins act at different sites in the chain of events that result in transmitter release. To find further evidence to support the different actions of the toxins the spontaneous transmitter release was studied in more detail. Tetx blocked preferentially the release of so-called large mode m.e.p.p.s without affecting the frequency of the small mode ones. In contrast, Botx strongly inhibited both the small and large mode m.e.p.p.s.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials

An assessment of the potential testicular toxicity of 10 pesticides using the mouse-sperm morphology assay.

Dinitrobutylphenol, chlorbenzilate, atrazine, Ordram, Telone (dichloropropene), pentachlorophenol (technical and reagent grades), Benomyl, DBCP (dibromochloropropane), and carbaryl were tested over a range of 7 doses in the mouse to assess their testicular toxicity. Measures of potential toxicity were sperm morphology, sperm counts and testicular weights. Each pesticide was injected intra-peritoneally in a single dose on each of 5 days. Testicular toxicity was assessed at 35 days. None of the pesticides tested, including the known human male testicular toxin, DBCP, produced statistically significant differences in the parameters from vehicle-injected controls.

Animals

Competitive and non-competitive interactions between specific ligands and beta-adrenoceptors in living cardiac cells.

We have used primary cultures of hearts from newborn rats to study beta-adrenoceptor properties in living myocardial cells. Receptors were labelled with the lipophilic antagonists 3H-(+/-)-carazolol and 125I-(+/-)-cyanopindolol (CYP) or with the hydrophilic antagonist 3H-(+/-)-CGP 12177. Under equilibrium conditions all ligands bound to a saturable homogeneous class of specific sites with a maximal binding capacity of approximately 100 fmol/mg protein (corresponding to approximately 5000 sites/cell). After 90-180 min preincubation of intact cells with 3H-carazolol or 3H-CGP 12177 only 80% of these antagonists could be displaced from specific binding sites by competing ligands. In the simultaneous presence of the antagonist (-) timolol 100% of specifically bound radiolabelled ligand remained displaceable. In competitive displacement experiments the radioligands did not affect the apparent affinity of the displacing nonlabelled antagonists timolol and CGP 12177, but agonist affinity was markedly changed. The apparent KD values for (-)-isoprenaline were 1560 and 2720 nmol/l in the presence of carazolol and CYP, but only 32 nmol/l in the presence of CGP 12177. This antagonist-dependent difference in agonist KD values was observed only in intact cells but not in membrane particles prepared from heart homogenates of newborn rats, where high agonist affinity was seen during displacement of all radioligands. The KA value for isoprenaline-stimulated cAMP accumulation in living cells was 30 nmol/l in 5-day cultures. A direct proportionality existed between agonist receptor occupation and cAMP accumulation in the presence of CGP 12177 as estimated by the KA/KD ratio. In the presence of carazolol the KA/KD ratio decreased from 1 to 0.02 suggesting that low affinity receptors were not coupled functionally to adenylate cyclase. These results indicate that some lipophilic antagonists which appear to be inert competitive ligands in fragmented membranes, alter receptor binding properties in intact cells. These antagonists seem to promote the transformation of receptor sites into a new "inactivated" state where competitive interactions between different ligands are inhibited.

Animals

[Clinically asymptomatic congenital macrofistular AV-aneurysm of the kidney].

Congenital arteriovenous aneurysms of the kidney are rare. The case of a now 65-year-old female patient is explained, in whom in 1971 during a renovasography on account of renal cyst at the left side of congenital arteriovenous aneurysm of the right kidney was established. Today - almost 10 years after the diagnosis and near her eight decennium of life - the patient is clinically symptom-free as to the untreated arteriovenous aneurysm of the right kidney. The observation shows that in arteriovenous aneurysms of the kidney cases with clinical relevancy and clinically asymptomatic cases must be differed.

Aged

Aspartylglycosaminuria in an Italian family: clinical and biochemical characteristics.

Two members of a consanguineous Italian family are described with symptoms of aspartylglycosaminuria. Both patients exhibit mental retardation, some facial dysmorphism and discrete radiological abnormalities affecting the skull and vertebrae. Peripheral blood smears revealed multi-vacuolated lymphocytes. Enzyme studies in leukocytes showed an absence of aspartylglucosaminidase activity. Urine analysis demonstrated abnormal oligosacchariduria. Angiokeratoma corporis diffusum was observed in one patient. The disease is seen as not being limited to Scandinavia or to patients of Scandinavian descent.

Acetylglucosamine

Disclosure of information to patients in medical care.

It is generally agreed that patients have a right to be adequately informed. However, little is known about the extent to which doctors and patients agree about information that should be disclosed. We studied what patients want to know, as contrasted with what physicians report actually disclosing, in a population of physicians who treat seizures and patients or parents of patients who have this disorder. In general, it was found that patients or parents of patients who have this disorder. In general, it was found that patients prefer far more detailed disclosures than physicians routinely offer and that the two groups have widely different beliefs about the consequences of detailed disclosures. Patients and parents preferred extensive disclosures, particularly regarding risks and alternative therapy. Physicians were likely to disclose only risks with a relatively high probability of occurrence and they provided little information about alternative therapies. Patients and parents were also much more likely than physicians to believe that the final decision concerning therapy should rest with the patient. The data suggest that a better empirical understanding of the consequences of detailed disclosures may help resolve differences of opinion regarding how much information should be provided to patients.

Adolescent

Disclosure standards and informed consent.

There is currently substantial disagreement about the kind of information that must be disclosed in obtaining an informed consent. This study examined physicians' interpretations of the demands of two alternative legal standards for disclosure, as well as a third standard intended to capture their normative sense of what should be disclosed to patients. Other factors which might affect disclosure practices of physicians were also studied. The findings raise questions about the extent to which a legal standard for disclosure can have an impact on medical practice; the data suggest that doctors currently disclose what they think patients want to be told. However, it appears that physicians substantially underestimate the amount of information patients wish to receive.

Disclosure

Clinical and biochemical delineation of aspartyl-glycosaminuria as observed in two members of an Italian family.

Two members of a consanguineous Italian family are described with the symptoms of aspartylglycosaminuria. Both patients exhibit mental retardation, some facial dysmorphism and discrete radiological abnormalities affecting the skull and vertebrae. Peripheral blood smears revealed multivacuolated lymphocytes. Enzyme studies in leucocytes and cultured fibroblasts showed an absence of aspartylglucosaminidase activity. Urinary analysis demonstrated abnormal oligosacchariduria and aspartylglycosamine excretion. Angiokeratoma corporis diffusum was observed in one patient.

Abnormalities, Multiple