Determination of cytoplasmic receptors for specific steroid hormones. III) Progestin receptor

A method for determining cytoplasmic progesterone receptor was standardized in normal human endometrium comparing two different tracers, 3H-progesterone (3H-P) and 3H-medroxyprogesterone acetate (3H-MAP), a synthetic progestin which does not bind to Corticosteroid Binding Globulin (CBG). Receptor assays were performed as previously reported for 17beta-estradiol receptor, with slight modifications: incubation lasted 1 hr at 0 degree C, followed by 5 min DCC exposure under the same conditions. When 3H-P was employed as tracer, blanks performed with cold MAP gave similar results as using cortisol in incubation tubes and progesterone and cortisol in blanks. 3H-MAP was a good tracer for progesterone receptor because it neither bound to CBG nor to androgen or cortisol receptors; it had very high affinity and specificity for P-R; it was not metabolized by cytosol at 0 degree C and, finally, it detected receptor amounts quite comparable to those obtained using 3H-P.     

Structural requirements of polynucleotides for the activation of (2'' - 5'')An polymerase and protein kinase.

Two enzymatic pathways are involved in the inhibitory effects of double-stranded (ds)RNA on protein synthesis in cell extracts derived from interferon-treated human fibroblasts or HeLa cells, an oligonucleotide polymerase that synthesizes (2'-5')An from ATP and a protein kinase that phosphorylates the alpha subunit of initiation factor eIF-2 as well as a polypeptide of Mr = 72,000. We have now evaluated the activation of both the (2'-5')An polymerase and protein kinase by a large variety of polynucleotides, triple-stranded and synthetic dsRNAs, homopolymers, alternating copolymers, triple-stranded polymers, purine-purine duplexes and purine-pyrimidine duplexes with modifications at either the pyrimidine or ribose moieties. All these polynucleotides have been the subject of previous interferon induction studies. Some polynucleotides, i.e. (I)n.(C)n and mycophage dsRNA, which have been recognized as excellent interferon inducers, were also potent activators of both (2'-5')An polymerase and protein kinase, whereas non-inducers such as (A)n. (X)n and (A)n. (br5U)n did not activate either the kinase or the polymerase. However, some polymers like (I)n.(br5C)n, (difl)n(C)n and (dIcl)n (C)n, while potent interferon inducers and kinase activators, behaved poorly as activators of the (2'-5')An polymerase. Other polymers, i.e. (dAfl)n (U)n and (A)n.(U)nl (I)n, that do not induce interferon, activated the kinase but not the polymerase. Finally, (I)n (s2c)n, a relatively potent interferon inducer, did not activate either kinase or polymerase. These findings indicate that there is no simple relationship between the interferon-inducing ability of dsRNAs and their stimulating effects on (2'-5')An polymerase and protein kinase activity.     

Sterols from three Lactarius species

The sterol composition of three fungi was determined. Ergosterol is the major sterol, accompanied by other closely related sterols.     

Epidémie de dysentérie bacillaire.

An outbreak of bacillary dysentery in 1978 affecting 928 persons, most of whom were living in the village of St-Jacques, PQ, is described. An epidemiologic study suggested the water supply as the source of the infection, and it was established that the water carried by the municipal aqueduct was contaminated by feces containing the causal agent, Shigella sonnei. This epidemic, the largest mentioned in he Canadian medical literature, demonstrates how contagious this infection is.     

Sister chromatid exchange induced by anti-herpes drugs.

The rate of sister chromatid exchange induced by several anti-herpes agents was measured to assess their potential mutagenicity. The agents--5-iodo-deoxyuridine (IDU), 5-trifluoromethyl-deoxyuridine (TFT), and [E]-5-(2-bromovinyl)-deoxyuridine (BVDU)--were incubated at various concentrations with human lymphocytes and fibroblasts, and that rate of sister chromatid exchanges was measured. In lymphocytes and fibroblasts BVDU and IDU did not induce exchange except at concentrations of 50 mg/l, while TFT increased the rate of exchange at a concentration of 0.5 mg/l. The rate of sister chromatid exchange is a sensitive index of chromosomal damage, and these findings provide information on the safety of some of the antiherpes agents tested. TFT increased the rate of exchange at a concentration that coincides with its minimal antiviral concentration, but BVDU did not induce exchange at therapeutic concentrations.     

Change and permanence: Reflections on the ethical-social contract of science in the public interest

Summary Modern science, dedicated since its 17th Century origins to the mastery and possession of nature for the relief of man's estate, is a source of great social change, affecting our opinions, practices, and ways of life. It thus exists necessarily in tension with law and morality, our institutions of stability and order. This tension between change and permanence, between science and law or morals, was institutionalized by the American Founders who sought to encourage, under law, the progress in science and the useful arts, by means of the copyright and patent laws. American science and technology have flourished under the patent law, an ingenious ethical and social contract between scientists and the polity, through which private right and interest and public good generally coincide. Nevertheless, this contract has its limitations. Some of these limitations are vividly seen through the recent Supreme Court decision (in the Chakrabarty case) to permit the patenting of living microorganisms. Analysis of this case shows why the contract between science and the polity embodied in the Patent Laws may not always serve the public good and may also be harmful to science itself. Also, permitting ownership of living species shows how close we have come in our thinking to overstepping the sensible limits of the project for the mastery and possession of nature.     

The use of Taka-diastase in a[3H]poly(A) hybridization assay of oligo(U) sequences in RNA

A reliable assay of uridylate sequences longer than 10 is described. The procedure is based on the hybridization of [3H]poly(A) with poly(U) or oligo(U) sequences in high ionic conditions and a subsequent degradation of single stranded polynucleotides with purified Taka-diastase. A 1:2 complex between poly(A) and poly(U) is formed on which on poly(U) strand is digested by Taka-diastase. The procedure is especially suitable for the detection and quantitation of Un (n greater than 10) in RNA preparation.     

The molecular weight of Artemia ribosomes, as determined from their refractive-index increment and light-scattering intensity

Cytoplasmic ribosomes were isolated from the cryptobiotic embryos of the brine shrimp Artemia salina. Measurements of their refractive-index increments and light-scattering intensities give a value for their molecular weight of (3.4±0.2)×10⁶.