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Biomedical subjects

N C Andrews

Publications and source records attributed to N C Andrews.

At least 73 records · Page 4Linked to original sources

Poliovirus replicase stimulation by terminal uridylyl transferase.

In an in vitro poliovirus replication system, purified viral polymerase, plus sense virion RNA, and a host factor have been previously shown to be necessary for the transcription of minus strands. We have found that a partially purified eukaryotic initiation factor-2 (eIF-2) fraction from rabbit reticulocytes can replace HeLa host factor in the replicase reaction. This enzyme preparation contains eIF-2 and two other major proteins. In addition to eIF-2 activity, which does not appear to play a role in the replicase reaction, we find that the fraction contains terminal uridylyl transferase activity. The enzyme adds UMP moieties to the 3' end of primer RNA molecules. The number of UMP residues added depends on the primer. Although long tails of heterogeneous lengths (50 to 100 nucleotides) can be polymerized on the 3' end of oligo(U), a poly(A) primer accepts only four U's. The terminal uridylyl transferase activity requires only UTP, Mg2+, a sulfhydryl reagent, and an RNA primer for activity. It is partially associated with ribosomes. We provide preliminary evidence that it may be responsible for host factor-like activity. We present a model for minus strand synthesis by poliovirus replicase, based on the hypothesis that a terminal uridylyl transferase can participate in initiation.

Base Sequence↗

Two small RNAs encoded by Epstein-Barr virus and complexed with protein are precipitated by antibodies from patients with systemic lupus erythematosus.

Primate cells harboring the Epstein-Barr virus (EBV) genome synthesize large amounts of two small RNAs:EBER 1 and EBER 2 (EBV-encoded RNA). These RNAs are approximately 180 nucleotides long, possess 5' pppA termini, and lack poly(A). They have different T1 and pancreatic RNase digestion fingerprints. They are not found in normal B lymphocytes, in transformed B lymphocytes that lack EBV DNA, in T lymphocytes transformed by Herpesvirus ateles, or in a variety of other nonlymphoid mammalian cells. Hybridization analyses indicate that EBER 1 and EBER 2 are encoded by the EcoRI-J fragment of EBV (B95-8) DNA. In vivo both RNAs are associated with protein(s), allowing their specific precipitation by the systemic lupus erythematosus-associated antibody anti-La. The La antigen in uninfected mammalian cells consists of a heterogeneous class of small ribonucleoprotein particles, some of whose RNA components exhibit sequence homology with a highly repetitive, interspersed class of human DNA designated the Alu family. Possible functions for EBER 1 and EBER 2 in infection and cell transformation by EBV and their potential relationship to the pathogenesis of systemic lupus erythematosus are discussed.

Antibodies↗

Continuing medical education tuition: a survey of charges.

A survey was carried out on the tuition charged for continuing medical education (CME) programs offered by a variety of providers. These included schools of medicine throughout the United States, national organizations and societies, state-wide organizations and societies located in California, and a small group of hospitals in or near Sacramento, California. The fees charged for continuing medical education (expressed in this article as the amount in dollars that a physician must pay for one hour of approved Category I credit) may vary from nothing to more than $20 an hour. The average charge per hour for CME courses sponsored by medical colleges in the United States ranged from none to $11.19 during 1976 and 1977. Recent data indicate that most schools have increased tuition for CME courses because of inflation. Many schools of medicine provide CME through grand rounds, conferences and special lectures at no cost to participants. Similarly, in a small sample of hospitals in California, CME was found to be available at a minimal charge to physicians. Some CME programs are more costly because fees may include the expenses of honored visiting faculty, and costs of food or social activities. There may be further expense if travel is required, although these additional costs may be offset by the benefits of study in a relaxed atmosphere away from practice and office pressures.

California↗

Yoshi 864 (NSC 102627) 1-propanol, 3, 3'-iminodi-dimethanesulfonate (ester) hydrochloride: a phase 1 study.

Yoshi 864 was given i.v. push daily times 5 with 6 weeks' followup. Dose escalation was from 0.25 mg/kg to 2.7 mg/kg. Toxicity and effectiveness were first seen at 1.5 mg/kg. Twenty-five courses were given to 16 patients at or above this level. In 16 of 22 courses, exclusive of CML, thrombopenia and/or leukopenia occurred. Mean platelet and WBC nadirs occurred on day 24 and 29 with recovery taking 1-2 weeks and 2-3 weeks respectively. Hb fell in 11 courses. At 2.7 mg/kg, nausea and vomiting lasting 6-12 days occurred in 3 of 7 courses; during 5 coures patients slept 20 hours a day, and 1 was comatose for 2 days. Two patients with squamous cell carcinoma and 1 with an unknown primary responded. Both patients with CML had clinical remissions. It is recommended that a cooperative Phase II Study in a broad spectrum of human solid tumors including lymphomas and chronic myelocytic leukemia be undertaken at a dose level of 2 mg/kg.

Alkylating Agents↗