A noncompetitive peptide inhibitor of the nicotinic acetylcholine receptor from Conus purpurascens venom

A paralytic peptide, psi-conotoxin Piiie has been purified and characterized from Conus purpurascens venom. Electrophysiological studies indicate that the peptide inhibits the nicotinic acetylcholine receptor (nAChR). However, the peptide does not block the binding of alpha-bungarotoxin, a competitive nAChR antagonist. Thus, psi-conotoxin Piiie appears to inhibit the receptor at a site other than the acetylcholine-binding site. As ascertained by sequence analysis, mass spectrometry, and chemical synthesis, the peptide has the following covalent structure: HOOCCLYGKCRRYOGCSSASCCQR* (O = 4-trans hydroxyproline; * indicates an amidated C-terminus). The disulfide connectivity of the toxin is unrelated to the alpha- or the alphaA-conotoxins, the Conus peptide families that are competitive inhibitors of the nAChR, but shows homology to the mu-conotoxins (which are Na+ channel blockers).     

Scientific and artistic investigation of multi-dimensional fractals on the AT & T pixel machine

The pipelined architecture and parallel organization of the AT&T Pixel Machine image computer are described and demonstrated with applications for the visualization of multidimensional fractals, particularly linear fractals and quaternion/ stacked Julia sets. Techniques for pushing the Pixel Machine to its peak abilities are described and apply to more recent parallel image computers as well.     

Long-term follow-up of a randomized post-induction therapy trial in acute myelogenous leukemia (a Southeastern Cancer Study Group trial)

A phase III clinical trial was designed to determine if more intensive induction and consolidation therapy for acute myeloblastic leukemia increases the remission rate and prolongs survival. A minor objective was to determine if the use of non-cross resistant drugs was more effective than the same drugs used for induction. Patients with untreated leukemia between the ages of 15 and 50 were given daunorubicin 45 mg/m2 for the first 3 days of a 10-day continuous infusion of cytosine arabinoside, initially at a dose of 2000 mg/m2 but reduced to 100 mg/m2 because of toxicity. Those under 36 achieving a complete remission and with an histocompatible donor were assigned to a transplant arm. The rest were randomized to receive one of three consolidation arms: A, cytosine arabinoside, 200 mg/m2 daily for 7 days and daunorubicin 45 mg/m2 daily for 3 days for three courses; B, one course as in Arm A followed by amsacrine, 120 mg/m2 daily for 5 days followed by a 5-day continuous infusion of azacytidine, 150 mg/m2/day; C, thioguanine and cytosine arabinoside, 100 mg/m2 every 12 h and daunorubicin 10 mg/m2 daily for 5 days for three courses followed by four maintenance courses of cytosine arabinoside, 100 mg/m2 daily for 5 days and daunorubicin, 45 mg/m2 for 2 days every 13 weeks. From 1981 to 1986, 398 eligible patients were enrolled and 219 achieved a complete remission. The initial induction dose of cytosine arabinoside was reduced after five of 29 patients exhibited fatal gastrointestinal toxicity. Only 11 patients were assigned to the transplant arm. There were no significant differences in the consolidation arms. The 5 year disease-free survivals were 38, 31 and 27% in arms A, B, and C respectively. Intensive consolidation therapy with the same or different drugs used in induction was as effective as lower dose consolidation followed by maintenance therapy.     

Dissipation in Mesoscopic Superconductors with Ac Magnetic Fields

The response of mesoscopic superconductors to an ac magnetic field is investigated both experimentally and with numerical simulations. We study small square samples with dimensions of the order of the penetration depth. We obtain the ac susceptibitity χ=χ′+iχ″ at microwave frequencies as a function of the dc magnetic field H _dc. We find that the dissipation, given by x″, has a non monotonous behavior in mesoscopic samples. In the numerical simulations we obtain that the dissipation increases before the penetration of vortices and then it decreases abruptly after vortices have entered, the sample. This is verified experimentally, where we find that χ″ has strong oscillations as a function of H _dc in small squares of Pb.     

Alpha 2 mRNA of Na+K+ ATPase is increased in astroctyes of rat hippocampus after treatment with kainic acid

The Na+K+ ATPase (Na+ pump) plays a central role in regulating cation homeostasis and is thought to have an important role in cell proliferation. The multitude of subunit isoforms comprising the functional Na+K+ ATPase has raised the possibility that specific subunit isoform combinations may be involved in different cellular processes. We have investigated the involvement of the specific isoforms in neurons and glia at the site of a CNS lesion. Intracerebroventricular injection of kainic acid was used to induce neuronal cell loss and reactive gliosis in rat hippocampus and levels of Na+K+ ATPase subunit isoform mRNA levels were determined in cells of rat hippocampus using in situ hybridization. alpha 2 mRNA levels increased 35-40% in CA1 and CA3 astrocytes between 1-3 weeks after KA injection with no significant change in other subunit isoform mRNA levels. In addition alpha 3 mRNA levels in CA1 pyramidal neurons were decreased by approx. 35%. Small neurons in the CA1 and CA3 region showed no changes in mRNA levels for any of the Na+K+ ATPase subunit isoforms. These results may indicate a possible role for alpha 2 subunit isoform in the conversion of glial cells from a normal phenotype to the reactive phenotype characteristic in this model of CNS injury.     

Single axioms for odd exponent groups

With the aid of automated reasoning techniques, we show that all previously known short single axioms for odd exponent groups are special cases of one general schema. We also demonstrate how to convert the proofs generated by an automated reasoning system into proofs understandable by a human.Authors supported by NSF Grant DMS-9100665     

A little less sodium is not without hazard

Surgical thrombectomy is not a rational approach to neonatal renal vein thrombosis since the occlusion mainly involves intrarenal branches rather than the main renal vein, which is even patent in some instances. Conservative management combines supportive therapy for renal failure and systemic hypertension, if needed, and either heparin or thrombolytic agents. Streptokinase has proven difficult to handle in neonates and should not be used. Urokinase has been used in 18 patients but results are difficult to interpret because these cases occurred over an 18-year period. Plasminogen tissue activator, the latest thrombolytic agent developed, has been used in few pediatric patients. An international task force is currently studying whether or not a randomized study is warranted to provide data for standardizing thrombolytic therapy in pediatric renal vein thrombosis.