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D Levin

Publications and source records attributed to D Levin.

87 records · Page 5Linked to original sources

Regulation of protein synthesis in reticulocyte lysates: phosphorylation of methionyl-tRNAf binding factor by protein kinase activity of translational inhibitor isolated from hemedeficient lysates.

A previous study demonstrated that the translational inhibitor from lysates of heme-deficient rabbit reticulocytes is associated with a protein kinase activity. Chromatography of this inhibitor preparation on phosphocellulose yields two distinct protein kinase activities, PC1 and PC2. PC1, which consitutes about 90% of the activity in the unresolved preparation, does not inhibit protein synthesis in lysates, but actively phosporylates calf thymus histone II in a 3':5'-cyclic AMP-denpendent reaction. PC2 contains the translational inhibitor, phosphorylates histone poorly, and is not cyclic AMP-dependent. While [gamma-32P]ATP as the phosphate donor, the two kinase fractions were analyzed with the putative substrates, salt-washed 40S ribosomal subunits, and the initiation factor that mediates the binding of Met-tRNAf to the 40S subunit. PC1 is inactive with the initiation factor, but phosphorylates 40S subunits at a single major site that migrates as a 31,000-dalton band in sodium dodecyl sulfate-acrylamide gels; phosphorylation requires cyclic AMP. Similar phosphorylation of the reticulocyte 40S site (31,000 daltons) can be demonstrated with other cyclic AMP-dependent kinases from reticulocytes, rat liver, and bovine heart muscle. PC2 phosphorylates the small subunit (38,000 daltons) but not the large subunit(s) of the initiation factor; the reaction does not require cyclic AMP. PC2 does not phosphorylate 40S subunits. In the presence of 40S subunits, the initiation factor appears to be rapidly bound in a manner that effectively blocks phosphorylation of the initiation factor by PC2; under the same conditions phosphorylation of the 40S subunit by PC1 is not affected. The initiation factor has been shown to reverse the inhibitions of protein chain initiation induced in lysates by heme deficiency, double-stranded RNA, oxidized glutathione, or the purified translational inhibitor. The observation that the Met-tRNAf binding factor is phosphorylated by PC2 supports the hypothesis that this initiation factor is a target for the action of the translational inhibitor activated in heme deficiency.

Cyclic AMP↗

The effect of an antimicrobial mouthwash on dental plaque and gingivitis in yound adults.

The effectiveness of an antimicrobial mouthwash (alexidine, 2-ethylhexyl bisbiguanidine dihydrochloride) in preventing plaque and gingivitis was evaluated in 45 young male adults. In a study using a double-blind cross-over design, subjects received a thorough prophylaxis and refrained from all routine oral hygiene for 2 weeks. During this period, subjects rinsed twice daily with either a treatment (alexidine) or placebo mouthwash. Plaque and gingivitis were assessed on selected teeth on days 2, 7 and 14. The characteristics of plaque that were recorded include: surface area score, dry weight and differential counts of microorganisms. After the 14th day, subjects resumed their regular oral hygiene practices for 3 weeks before starting the second experimental period. Aftter a second prophylaxis, the treatment and placebo groups from the first 2 weeks were crossed over and the procedures followed previously were repeated during the sixth and seventh weeks. The alexidine mouthwash was statistically and clinically effective in decreasing plaque scores and plaque weight, and statistically but not clinically effective in decreasing gingivitis scores. No systemic side effects were observed, but an asymptomatic brown tongue stain was observed in about half of the subjects. There was no evidence to suggest that alexidine disturbed the relative composition of the microorganisms in plague, but there was a suggestion that it decreased the number of microorganisms almost 2-fold when compared with the placebo group.

Adult↗

Dose-sensitive excitation and inhibition of spontaneous amygdala activity by propranolol.

The effect of systemically administered propranolol was determined on spontaneous activity of neurons in the central nucleus (CeA) of the amygdala, a brain site implicated in fear-related learning and memory. Extracellular recordings of single units in the CeA were obtained in vivo from rats administered saline or the centrally and peripherally acting beta-adrenergic receptor blocker propranolol (4, 7, 10 mg/kg i.p.). The high dose (10 mg/kg) of propranolol markedly increased spontaneous activity of CeA neurons. In contrast, the low (4 mg/kg) and intermediate (7 mg/kg) doses of propranolol significantly decreased spontaneous CeA activity, with the suppressant effect of propranolol on CeA firing rates weakening as the dosage increased from 4 to 7 mg/kg. These results suggest that (1) spontaneous activity of CeA neurons is tonically influenced by competing excitatory and inhibitory modulatory circuits, and (2) propranolol's effect on the two modulatory circuits is dose dependent: the high dose increasing spontaneous CeA activity by preferentially blocking an inhibitory circuit, the low dose decreasing spontaneous CeA activity by preferentially blocking an excitatory circuit, and the intermediate dose weakly suppressing CeA activity by blocking both the excitatory and inhibitory modulatory circuits. Disinhibition of CeA activity by the high dose of propranolol may explain the enhancement of retention observed in the passive-avoidance task when this dose of the drug is administered systemically, and may have implications for the use of propranolol clinically in treating aversive-memory-related anxiety disorders such as posttraumatic stress syndrome.

Adrenergic beta-Antagonists↗

The passage of granulocyte-macrophage colony-stimulating factor across the human placenta perfused in vitro.

OBJECTIVE: The purpose of this study was to investigate the placental passage of granulocyte-macrophage colony-stimulating factor in a placental perfusion model ex vivo. METHODS: In an open system, 11 placentas were perfused on both the maternal and the fetal side immediately after delivery. Granulocyte-macrophage colony-stimulating factor was added to the maternal perfusion medium in concentrations from 10-55 micrograms/mL. Maternal and fetal samples were taken, and granulocyte-macrophage colony-stimulating factor (GM-CSF) was measured by enzyme-linked immunosorbent assay. RESULTS: Accumulation of granulocyte-macrophage colony-stimulating factor in the fetal circuit averaged 2.42% of the concentration added initially to the arterial portion of the maternal circuit. CONCLUSION: There is only low transfer of GM-CSF across the fetal membranes. This finding is particularly remarkable in view of recently published results suggesting that administration of recombinant granulocyte growth factors to pregnant women with imminent preterm delivery helps prevent neonatal sepsis.

Arteries↗

A public health response to emerging technology: expansion of the Massachusetts newborn screening program.

The development of a new technology, called tandem mass spectrometry (tandem MS), has challenged governments worldwide to consider expanding universal newborn screening for rare metabolic disorders. In 1997 the Massachusetts Department of Public Health developed a public process to meet this challenge. After addressing significant medical, legal, ethical, and logistical issues raised by tandem MS, Massachusetts incorporated one new disorder into the mandatory newborn screen and developed an optional pilot program for 20 additional disorders. The Massachusetts experience has wide relevance for other nations and states. As screening protocols are contemplated for entire populations-for newborns and others- it will remain essential that the public participate in an open process of reviewing the justification for and logistics of screening.

Ethics, Medical↗

The cost-effectiveness of same-day admission surgery.

The move toward outpatient and same-day surgical services has been phenomenal in recent years. In this study comparing same-day and traditional surgery patients in a Midwest tertiary care center, hospital charges and costs were significantly lower for same-day surgery patients. These differences reflected decreased lengths of stay and reduced ancillary services.

Adult↗

Electrophysiological effects of low dose alcohol on human subjects at high altitude.

Low dose alcohol significantly altered auditory evoked potentials in normal human subjects. Effects of alcohol were studied on the P50 evoked potential wave following click stimulation, which was presented in a conditioning-testing paradigm. The conditioning-testing paradigm uses paired stimuli to demonstrate inhibitory sensory gating, measured as suppression of the amplitude of the second or "test" response following the first or "conditioning" response. Alcohol at blood levels under 0.1 g per dl caused significant decrement in the size of the P50 wave in the initial conditioning response and also decreased the suppression normally seen in the conditioning-testing paradigm. These data suggest that low doses of alcohol affect both the excitatory mechanisms responsible for the formation of the P50 wave in the conditioning response and the inhibitory mechanisms responsible for its suppression in the test response. Nine of the 17 subjects studied using this paradigm were recorded both at Denver, Colorado (5,280 feet above sea level) and on Mt. Evans (14,264 feet above sea level). Despite the commonly held belief that alcohol causes more intoxication at high altitudes there was no significant difference in the effects of alcohol on evoked potentials in these subjects at these two attitudes.

Adult↗