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Biomedical subjects

A Levy

Publications and source records attributed to A Levy.

At least 433 records · Page 24Linked to original sources

Radial arm maze performance of mice: acquisition and atropine effects.

CD-1 mice were successfully trained in a six-arm radial maze in which half of the arms were baited, a procedure which had been used to differentiate between reference and working memory. Stable performance was achieved following eight daily training sessions, as measured by decreasing running time and number of errors. This finding strengthens the foraging hypothesis as a basis for the performance of rodents in the radial maze. Acute subcutaneous administration of the cholinergic antagonist atropine sulfate (1-6 mg/kg) to trained mice produced dose-related increases in running time and working memory errors, with a slight decrease in reference memory errors. This is in agreement with other studies on the role of the cholinergic system in memory processes. The peripheral cholinergic blocker, atropine methyl nitrate (4 mg/kg), somewhat increased running time without decreasing performance accuracy. In contrast to the prolonged pharmacological and physiological effects of atropine, behavioral decrements disappeared within 3 hr. It is concluded that mice trained in the radial arm maze may be used for screening of the effects of drugs on cognitive function.

Animals↗

Studies on bleomycin-DNA and bleomycin-iron interactions.

The bleomycins, a group of antitumor antibiotics (Figure 1), cause the degradation of DNA by a process requiring iron(II) and dioxygen (1,2). DNA degradation appears to involve two steps: association of the drug with the nucleic acid and degradation of the DNA. As part of studies directed toward achieving an understanding of how the bleomycins degrade DNA, we have examined various properties of the drug using a variety of chemical and physico-chemical techniques, including NMR and Mössbauer spectroscopy. We have studied both the interaction of the antibiotic with its target (DNA) as well as its association with its metal ion cofactor. This work has been performed on the intact drug and its derivatives as well as on synthetic models of the parent drug. This paper reviews and updates the recent work from this laboratory on the bleomycins.

Binding Sites↗

Superiority of oral verapamil therapy to digoxin in treatment of chronic atrial fibrillation.

The efficacy and safety of oral verapamil, 240 mg, with or without digoxin were studied in 52 patients with chronic atrial fibrillation at rest, and during mild and maximal exercise. Twenty-four patients were studied during the following therapeutic modalities: no therapy; digoxin, 0.25 mg and 0.5 mg daily; digoxin, 0.25 mg and verapamil; and verapamil alone. Heart rate at rest and during all levels of exercise was decreased significantly (p less than 0.005), either by combining digoxin with verapamil or by verapamil therapy alone. In contrast, the excessive heart rate response to exercise was not prevented by digoxin even with good serum concentrations. The improved control of heart rate with verapamil was associated with a significantly improved exercise capacity. Verapamil is an important and safe modality of treatment, with or without digoxin, in the long-term control of heart rate in chronic atrial fibrillation. It is superior to digoxin in controlling the ventricular rate and in improving exercise capacity.

Administration, Oral↗

[Open study of bromapezan in ambulatory and psychiatric hospital patients (author's transl)].

Psychiatrists working in hospital and in private practice took part in co-operative trial aimed at evaluating the effectiveness and safety of bromazepam. The study was of the open type and involved 10 hospital patients and 20 ambulatory patients. The same protocole was followed for each patient. Twenty-five patients (including 5 in hospital) had anxiety neurosis; the remaining 5 had anxiety following weaning from alcohol. The anxiolytic effects of the drug, determined by means of Hamilton's anxiety scale and overall clinical judgement, were generally found to be satisfactory. The effective doses ranged from 1 to 3 tablets per day in ambulatory patients and from 3 to 5 tablets per day in hospital patients. The main side-effects were related to unwanted sedation; they only occurred with the higher doses and rarely interfered with the beneficial effects of bromazepam.

Adult↗

[Value of neonatal screening for cystic fibrosis. Evaluation of a neonatal screening program including 34,522 neonates (author's transl)].

Screening for cystic fibrosis in 34,522 neonates was done by assaying proteolytic activity in feces samples spread on special filter paper. Infants were considered at high risk for cystic fibrosis if proteolytic activity was significantly decreased and albumin was found in all the fresh stool specimens. Cystic fibrosis was detected in eight infants, most of whom were already hospitalized for respiratory and/or digestive manifestations suggestive of the disease. Six other patients, one of whom was three-and-a-half years-old, were detected after referral by pediatricians. Two false-negative results were recorded, in infants without detectable pancreatic involvement. Given these results, the authors believe that routine neonatal screening for cystic fibrosis is unnecessary. The various etiopathogenetic mechanisms and the possibilities for investigating patients with cystic fibrosis are discussed.

Clinical Enzyme Tests↗

The effect of chronic lithium pretreatment on rat brain muscarinic receptor regulation.

The effect of two weeks of lithium (Li) pretreatment on up and down regulation of muscarinic receptors in rat brain was measured in two groups of rats. After two weeks of feeding 0.2% LiCL in ground pellets, one group of rats was injected with atropine (3 mg/kg daily for 5 days) and another group with diisopropyl fluorophosphate, a cholinesterase inhibitor (1.2 mg/kg). Li pretreatment completely abolishes the significant 23% rise in QNB binding induced by atropine but does not prevent the significant 16% decline in QNB binding induced by DFP. These results suggest that chronic Li pretreatment prevents supersensitivity but does not prevent subsensitivity of rat brain muscarinic receptors.

Animals↗

Chromosomal instability in NZB/BL mice. A dominant trait.

The descendance of 2 lines from NZB/bl mice which differ by the frequency of chromosome breaks has been studied. The analysis of reciprocal crosses and of "back cross" shows that the character of the chromosome breaks is perhaps dominant. This result is correlated with the observation that the autoimmunity (17) and viral expression (1, 13, 17) are also dominant.

Animals↗

Changes in chromatin structure at the replication fork. II The DNPs containing nascent DNA and a transient chromatin modification detected by DNAase I.

Discrete deoxyribonucleoproteins (DNPs) containing nascent and/or bulk DNA, were obtained by fractionating micrococcal nuclease digests of nuclei form 3H-thymidine pulse (15-20 sec) and 14C-thymidine long (16 h) labeled sea urchin embryos in polyacrylamide gels. One of these DNPs was shown to contain the micrococcal nuclease resistant 300 bp "large nascent DNA" described in Cell 14, 259-267, 1978. The bulk and nascent mononucleosome fractions provided evidence for the preferential digestion by micrococcal nuclease of nascent over bulk linker regions to yield mononucleosome cores with nascent DNA. DNAase I was used to probe whether any nascent DNA is in nucleosomes. Nascent as well as bulk single-stranded DNA fragments occurred in multiples of 10.4 bases with higher than random frequencies of certain fragment sizes (for instance 83 bases) as expected from a nucleosome structure. However, a striking background of nascent DNA between nascent DNA peaks was observed. This was eliminated by a pulse-chase treatment or by digestion of pulse-labeled nuclei with micrococcal nuclease together with DNAase I. One of several possible interpretations of these results suggests that a transient change in nucleosome structure may have created additional sites for the nicking of nascent DNA by DNAase I; the micrococcal nuclease sensitivity of the interpeak radioactivity suggest its origin from the linker region. Endogenous nuclease of sea urchin embryos cleaves chromatin DNA in a manner similar to that of DNAase I.

Animals↗

Chromatin fine structure of active and repressed genes.

Study of the structural organization of chromatin during transcription and replication may reveal important aspects of these processes. At the lowest level of organization, chromatin consists of a repeating subunit, the nucleosome (for reviews see refs 1-3). Electron microscopy indicates that the nucleosomes are arranged helically or form discrete superbeads, generating the familiar 250 A-300-A fibre. It has been suggested that this fibre is further folded into loops containing up to several hundred nucleosomes. Despite extensive study, the significance and fate of these nucleosomes remain obscure. We have used here micrococcal nuclease digestion to compare the structures of actively transcribing and inert chromatin of the genes coding for the major heat-shock protein of Drosophila melanogaster. The repressed hsp 70 genes were considerably more resistant to cleavage by micrococcal nuclease than their flanking regions and the bulk of chromatin. The active genes, previously shown to be more sensitive than the repressed genes, are also more susceptible to the nuclease than their 3'-flanking regions and bulk chromatin.

Animals↗

Benzene in blood and phenol in urine in monitoring benzene exposure in industry.

Determinations of benzene concentration in blood and of phenol in urine were made by head-space gas chromatography techniques on samples taken near the end of the work day from two groups of workers potentially exposed to low levels of benzene in the work-place atmosphere. Preliminary results suggest that benzene in blood is more reliable than phenol tests for assessing both exposure and uptake of benzene. Normal values of phenol in urine (10 mg/liter or less) were found in nearly all those cases in which benzene was detected in the blood.

Benzene↗

Isolation and partial characterization of secreted hamster pituitary prolactin.

PRL secreted by hamster anterior pituitaries was purified by gel filtration on Sephadex G-100 and ion exchange chromatography on DEAE-cellulose. Hamster PRL eluted from Sephadex G-100 with an elution volume to void volume ratio of 1.85 and at a salt concentration of 0.13 M NaCl on DEAE-cellulose. Electrophoretic homogeneity of the hormone was demonstrated in several gel systems, and electrophoresis in the presence of sodium dodecyl sulfate indicated a molecular weight of 22,000 +/- 2,000. Hamster PRL did not cross-react with antiserum to mouse PRL. Hamster PRL displayed lactogenic activity in an in vitro mouse mammary gland assay. Hamster PRL displaced [125I]iodo-PRL from lactating rabbit mammary gland receptors. Thus, with respect to its exclusion properties on SEphadex G-100, its molecular weight, and its biological activity, hamster PRL closely resembles other mammalian PRLs.

Animals↗