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L Brown

Publications and source records attributed to L Brown.

At least 361 records · Page 20Linked to original sources

Evidence for a serotonergic mechanism of the learned helplessness phenomenon.

The present experiments examined the role of the serotonergic system in the learned helplessness phenomenon. In Experiment 1, a 200 mg/kg dose of 1-tryptophan injected 30 min prior to testing disrupted acquisition of Fixed Ratio 2 shuttle escape behavior. In Experiment 2, a 100 mg/kg dose of 5-HTP produced interference with the acquisition of the escape response. Furthermore, this interference was prevented by treatment with the serotonergic antagonist methysergide. In Experiment 3, animals were pretreated with a subeffective dose of 1-tryptophan in combination with subeffective exposure to inescapable shock. These animals showed a deficit in the acquisition of FR-2 shuttle escape. In Experiment 4, combined exposure to a subeffective dose of 5-HTP and inescapable shock (40 trials) resulted in an acquisition deficit. This deficit was reversed by methysergide. Experiment 5 showed that the detrimental effects of exposure to prolonged (80 trials) of inescapable shock can be prevented by treatment with methysergide. These studies implicate the serotonergic system as a possible mediator of the learned helplessness phenomenon.

Animals↗

Cardenolide analogues. 14. Synthesis and biological activity of glucosides of C17 beta-modified derivatives of digitoxigenin.

An improved method for the synthesis of cardiac glycosides was used to prepare 3 beta-glucosides of digitoxigenin derivatives in which the 17 beta side chain was CH=CHX (X = COOH, CONH2, COCH3, CN, or COOR). We compared the inotropic activity of the compounds with that of digitoxigenin glucoside using guinea pig left atria. All compounds were active except for the acid (7) and the amide (8). The inactivity of the amide, in spite of its favorable shape and high capacity for forming intermolecular hydrogen bonds, is incompatible with some previous structure-activity relationship theories. Of the active genins, glucosidation enhanced activity by a factor of about 2. All glucosides, including those with high potency, showed rapid onset and offset of action. The stepwise fall in potency that occurred when the ester group (CH=CHCOOR) was increased in bulk supported previous suggestions that the portion of the digitalis receptor that interacts with the C17 side chain lies within a cleft.

Animals↗

Antibiotics.

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Anti-Bacterial Agents↗

Recombination occurs mainly between parental genomes and precedes DNA replication in pseudorabies virus-infected cells.

The experiments described in this paper were part of an attempt to determine the mechanisms involved in the isomerization of the pseudorabies virus genome. To this end, [(14)C]thymidine-labeled parental virus DNA that was transferred to progeny virions produced by cells incubated in medium containing bromodeoxy-uridine was analyzed in neutral and alkaline CsCl density gradients. The buoyant density of the (14)C-labeled DNA indicated that the parental DNA strands had retained their integrity and had not undergone breakage and reunion with progeny DNA strands; neither massive intermolecular nor intramolecular recombination had occurred after replication of the DNA. Whereas breakage and reunion between parental and progeny virus DNA strands were not detectable, these processes were observed between differentially density-labeled parental DNAs. Furthermore, the frequency of recombination between progeny DNAs accumulating in the cells was low. These results indicate that in pseudorabies virus-infected rabbit kidney cells recombination occurs mainly between parental genomes and precedes DNA replication. An analysis of the kinetics of appearance of recombinants between pairwise combinations of temperature-sensitive mutants also indicated that recombination is an early event. The ratio between the number of recombinant virions and the number of temperature-sensitive mutant virions produced by the cells remained the same throughout infection. Since the relative amounts of viral DNAs synthesized early and late during the infective process that were integrated into virions were approximately the same, it appears that late viral DNA did not experience an increased number of recombinational events compared with early viral DNA. These results, which reinforce the conclusion reached from the results of the analysis of the behavior of the parental DNA molecules in density shift experiments, indicate that recombination is an early event.

Animals↗

Normal sister chromatid exchange frequency in long-term survivors with acute leukemia.

We hypothesized that the sister chromatid exchanges assay in acute leukemia long-term survivors may detect: (a) long-term effects of combined chemo- and radiotherapy; and possibly (b) those individuals with inherently deficient DNA repair. Accordingly, we determined the sister chromatid exchanges frequency in 26 blood specimens from 24 acute leukemia long-term survivors (patients) and 14 blood specimens from 13 control subjects (controls). The patients consisted of 23 children with acute lymphocytic and one child with acute myelocytic leukemia. The median length of chemotherapy was 5 years. Eighteen of the 24 patients also received prophylactic fractional central nervous system irradiation for the first 3 years of treatment, and one patient received therapeutic irradiation to the central nervous system. The median off-therapy period at the time of study was 2.5 years with a range of 0 to 7.5 years. The controls consisted of the parents of the patients and laboratory personnel. A mean exchange score per cell was established for each specimen (25 to 30 cells/specimen were scored), and it ranged from 3.0 to 9.7 in the patients and from 3.0 to 11.5 in the controls. A mean +/- S.D. calculated from those means was 6.0 +/- 1.8 for the patients and 6.9 +/- 2.8 for the controls. They were not significantly different. We conclude that chemo- and radiotherapy produced no persistent DNA alterations detectable by this method.

Child↗

Localized duodenal lymphoma masquerading as a duodenal ulcer.

A 64-year-old woman presented with atypical abdominal pain, weight loss, melena and hematemesis. Reactivation of a peptic ulcer was diagnosed and she was treated with antacids and cimetidine. When her symptoms recurred 4 months later, a perforated duodenal ulcer was noted on roentgenograms. At laparotomy this proved to be a perforated, localized lymphoma of the duodenum. This case highlights an important consideration in the management of duodenal ulcers. Patients who present with a previously diagnosed peptic ulcer, who demonstrate atypical symptoms and remain refractory to treatment should undergo endoscopic examination and biopsy to rule out an occult localized duodenal lymphoma.

Biopsy↗

Cardenolide analogues. 11. Improved method for the use of Fétizon's reagent in the synthesis of cardiac glycosides.

An improved procedure has been developed for preparing glycosides of cardenolide genins. The method uses specially prepared Fétizon's reagent as catalyst, combined, in most cases, with mercuric cyanide and mercuric bromide. In the presence of this catalyst, genins react readily, at room temperature, with per-acetylated 1-bromo-sugars to give the acetylated glycosides in high yield with little or no side reaction. The reaction proceeds almost to completion in 30 to 60 min. The free glycoside is obtained by mild deacetylation using triethylamine/methanol/water (20:20:1) at room temperature for 72 h. Proof of structure was obtained using chemical ionization mass spectrometry, NMR spectroscopy and comparison of physical constants with published data. The compounds were tested for inotropic activity using the isolated guinea pig atrium.

Animals↗

A murine C4 molecule with reduced hemolytic efficiency.

C4 functional activity and antigenic levels were determined in H-2-congenic mouse strains. In strains with the H-2w7 haplotype, the C4 hemolytic activity per unit of residual Ss antigenic activity, after depletion of the nonfunctional Slp-positive molecules was 25-33% that found with other H-2 haplotypes. This reduced hemolytic efficiency was not the result of either a more labile C4 molecule or of the presence of inhibitors. Moreover, other strains with comparable antigenic concentrations of Ss (C4) and Slp has three- to fourfold higher levels of C4 hemolytic activity. Based on these data and previously reported structural differences between C4 molecules from the H-2w7 haplotype compared with other standard H-2 haplotypes, the reduced hemolytic efficiency of this molecule is probably secondary to alterations in the structure of its alpha-chain.

Animals↗

The inhibition of high and low molecular weight urokinase in plasma.

The rates of inhibition of high molecular weight (HMW) and low molecular weight (LMW) urokinase (UK) incubated in plasma or with purified antithrombin III (AT-III) were compared. Using a fibrinolytic assay system to determine residual biologic activity, polyacrylamide gel electrophoresis to demonstrate the formation of complexes, and selective immunoprecipitation techniques to identify the plasma inhibitors participating in the neutralization process, it was established that: (A) HMW-UK is inhibited more rapidly than LMW-UK, both in plasma and with purified AT-III; (B) heparin (3--10 U/ml accelerates the neutralization process in both systems, but only slightly; and (C) in plasma, several inhibitors, alpha 2-macroglobulin, alpha 1-antitrypsin, and antithrombin III, neutralize the activity of HMW-UK and LMW-UK.

Animals↗