S-Tubercidinylhomocysteine (STH) is a structural analog of S-adenosylhomocysteine and a potent inhibitor of S-adenosylmethionine-dependent methyltransferase reactions. We investigated the effects of STH on HeLa cell mRNA metabolism. Dual

No abstract

PROBLEMThis study investigated the performance of hospitalized alcoholics and normals on a measure of time perspective, the Time Reference Inventory2 (TRI). Specifically, the study attempted to answer the question: Do alcoholics differ from normals in their orientation toward the past, present and future?Alcoholics have been described as dominated by the need for immediate gratification(3* ll. 12. 1 4 ) , pessimism toward the future('O* 17), and inability to maintain long-range goals(7. 8. l6. 17. l 9 ) . It was hypothesized, therefore, that alcoholics would differ from normals in being less concerned with long-range aspects of the future. Alcoholics have also been found to exhibit low ego strength('. 4. 16. '81, resistance to introspection(14. 21), and inability to accept frustration or tensionc2' 3. '9, 20, 23). These characteristics led to the hypothesis that alcoholics mould differ from normals in their orientation toward past and present. Although clinical impressions leading to these hypotheses appear to be generally consistent, experimental verification has been lacking. Clarification of the nature of the temporal orientation of the alcoholic would add significantly to the understanding of the condition and would have implications regarding the relative effectiveness of therapeutic approaches. METHODSubjects. Thirty-five patients (31 males and 4 females) hospitalized in a neuropsychiatric state hospital with a psychiatric diagnosis of alcoholism (E group) were compared with 24 psychiatric aide applicants and 3 hospital volunteers who did not manifest symptoms of psychiatric derangement (C group; 5 males and 22 females). The two groups did not differ in intelligence (mean I& for alcoholics was 95.51, for normals 99.37), age (mean age for alcoholics was 48.20, for normals 47.33), and educational level. A previous exploratory study of 77 normals revealed no significant sex differences on pertinent variables of the TRI.Proczdure. The TRI is a 30-item paper-and-pencil questionnaire designed by the senior author to evaluate temporal orientation ( 1 3 ) . The subject indicates for each item whether it most appropriately refers to his past, present, or future. He then estimates his age at the time he feels the item most appropriately applies. For items selected as applying to the present, he lists his chronological age. The first ten statements refer to pleasant or positive events; the second ten refer to unpleasant or negative events, and the last ten refer to affectively neutral events. The following items from the TRI are representative : Item 1.

S-Tubercidinylhomocysteine (STH) is a structural analog of S-adenosylhomocysteine and a potent inhibitor of S-adenosylmethionine-dependent methyltransferase reactions. We investigated the effects of STH on HeLa cell mRNA metabolism. Dual labeling studies reveal that STH dramatically inhibits the methylation of HeLa mRNA in a dose-dependent manner. Analysis of the modified nucleosides and 5'-terminal cap structures in radiolabeled mRNA by high-pressure liquid chromatography indicated that internal N6-methylation of adenosine was reduced by 65% at 50 microM STH and by 83% at 500 microM STH. The N6-methylation of adenosine contained in cap structures was similarly reduced at both concentrations of STH. Substantial amounts of cap structures lacking 2'-O-methylated nucleosides (m7GpppN, cap zero) were detected at the higher level of STH. To test the possibility that methylation affects mRNA stability, cytoplasmic mRNA half-life was measured in a pulse-chase experiment. The half-life of undermethylated mRNA, produced as a consequence of STH treatment, was unchanged compared with the control. To determine whether mRNA methylation is coupled to nuclear processing or transport, the time of cytoplasmic appearance of polyadenylated RNA in STH-treated HeLa cells was compared with untreated cells. STH caused a significant lag in the time of appearance of the polyadenylated RNA, suggesting that mRNA methylation may be required for efficient processing or transport.

The self-association of A-methylacetamide in carbon tetrachloride solution at 25°was found to be described by the relationship = Mi/(1 + 4kc)'^-+ BMxc + ICMxC, where and c are the apparent weight-average molecular weight and solute concentration (grams per milliliter) and the constants Mu k, B, and C, corresponding to the monomer molecular weight, indefinite association constant, and second and third virial coefficients, had values of 73 g/mol, 2.68 ± 0.15 X 104 56789ml/g, 0.0312 ± 0.0036 mol/ml, and 0.0970 ± 0.0201 mol/ml2, respectively. The average aggregation number of a 0.3 m solution was 66, and pure A'-methylacetamide was estimated to contain 0.39 % monomer.It is shown that peptide hydrogen bonds would tend to stabilize polypeptides and helical proteins if an indefinite association is used as a model system.111., Sept 1970.