Alternatives to estrogen for the treatment of hot flashes.

Postmenopausal women experiencing hot flashes in whom estrogen replacement is contraindicated have alternatives available to them; however, there is no clearly defined treatment modality. The literature addressing many of these alternatives has serious limitations, which include the small number of women enrolled and lack of comparative studies between agents. Each patient needs to be assessed in terms of her current medical status, concomitant medications, and the degree to which vasomotor instability interferes with everyday activities. The literature suggests that megestrol acetate 20 mg bid may provide significant relief. Women who opt to use megestrol acetate must be told in advance that the effects will not be felt immediately particularly if tamoxifen is used concomitantly. Clonidine and medroxyprogesterone may constitute potential alternatives, but patients may not be able to tolerate the adverse effects. Because of the lack of literature supporting their clinical use, options such as vitamin E and ginseng need to be approached cautiously. Exercise has a role in alleviating some of the complications associated with menopause, such as heart disease and osteoporosis, but its effect on neurotransmitters and hormone concentrations, and how this relates to the treatment of hot flashes have not been characterized. Patients should be told that regular physical activity, a balanced diet, avoidance of alcohol and caffeine, and stress reduction may be of additional help in decreasing vasomotor flushing.

Interaction of DNA-binding proteins with the tissue-specific human apolipoprotein-AII enhancer.

The identification of the binding sites for liver nuclear proteins present in the enhancer that control the cell specific transcription of the human apolipoprotein AII gene is reported. Five adjacent binding sites (motifs I to V) were identified. The motifs III, IV and V can be occupied differently by liver or HeLa nuclear proteins. Two hypersensitive zones (between motifs II-III and IV-V) are present only when liver nuclear extracts were tested. A first characterization of the factors reveal that motif IV interacts with the hepatic transcription factors Tf-LF1 (29) and LF-A1 (28, 30). A CCAAT binding protein, different from CTF/NF1, appears to bind to the motif II. The different binding sites share specific DNA sequences principally with 5' regulatory regions of other apolipoprotein genes.

Molecular structure and early events in the replication of Tacaribe arenavirus S RNA.

Tacaribe arenavirus S RNA was cloned and analysis of its nucleotide sequence revealed two open reading frames of significant size, one in the virus-sense strand, the other in the virus-complementary strand. The predicted amino acid sequences of the two reading frames were compared with the predicted primary structures of the nucleoprotein (N) and glycoprotein precursor (GPC) of LCM, Pichinde and Lassa viruses. The results indicated a high degree of homology between the proteins of similar properties. It was also found that in Tacaribe virus-infected cells a subgenomic viral-sense GPC RNA and a subgenomic viral-complementary N RNA are synthesized in addition to the full length viral (v) RNA and viral complementary (vc) RNAs. These results support the conclusion that in Tacaribe virus--as in Pichinde and lymphocytic choriomeningitis arenavirus-S RNA encodes the viral N and GPC proteins and has an 'ambisense' coding strategy. Analysis of the S-derived RNA species at early times post-infection in cells incubated with or without inhibitors of protein synthesis indicated that for primary transcription of the N mRNA, protein synthesis is not required; whereas synthesis of the vc RNA, GPC mRNA and v RNA does require protein synthesis to take place.

Complete structure of the human transferrin gene. Comparison with analogous chicken gene and human pseudogene.

The complete structure of the human transferrin gene is presented. This gene has a total size of about 33.5 kb and is organized in 17 exons separated by 16 introns. The chicken ovotransferrin gene has a size of 10.5 kb and is also organized in 17 exons and 16 introns. The analysis of the structure of the two genes confirm, at the gene level, that transferrins originated by a gene duplication phenomenon. Finally, the existence of a new member of the transferrin family, a human transferrin non-processed pseudogene is demonstrated.

Human apolipoproteins AI, AII, CII and CIII. cDNA sequences and mRNA abundance.

The structure and function of the genes encoding the polypeptide components of plasma lipoproteins are of interest because of the central role they play in the regulation of lipid metabolism. We have now completed our previous studies on the human apoAI gene and furthermore isolated and sequenced cDNA clones for apoAII , CII and CIII. The nucleotide sequences show the signal peptides of apoAII , CII and CIII to be 18, 22 and 20 amino acids in length, respectively, and in addition that prepro apoAII bears a classical propeptide structure of 5 amino acids. The amino acid homology detected between apoCII and pro- apoAI is discussed, as is the gene arrangement of the 5' non-coding region of apoAI mRNA. The relative liver mRNA levels of the 4 apolipoproteins analysed in this study have been estimated and compared with their corresponding plasma products. The data reported here provide an essential basis for further studies of structural and functional alleles of apo AI, AII, CII and CIII genes.

The Alu family repeat promoter has a tRNA-like bipartite structure.

The essential sequences needed for Alu repeat transcription by RNA polymerase III were mapped. Experimental evidence is presented showing that the Alu repeat promoters are organised in a bipartite structure similar to the split tRNA promoters as suggested by DNA sequence homology. Furthermore, by combining fragments from efficiently and inefficiently transcribed natural Alu repeats in several recombinant clones, it was possible to investigate the regions responsible for their differences. It is clear that, apart from the short stretches of homology with the tRNA consensus sequence, there is very little constraint in the promoter sequences. However, our studies indicate that some influence on the efficiency of transcription may be exerted by regions outside the accepted promoter components.

Comparison of effects of leukocyte and fibroblast interferon on immunological parameters in cancer patients.

Patients with metastatic cancer were given single intramuscular injections of 10(7) units of partially purified preparations of either leukocyte or fibroblast IFN. Serum levels of inteferon, of beta 2-microglobulin and of carcino-embryonic antigen (CEA), as well as NK activity of circulating lymphocyte, were followed over a period of 96 hr post injection. In confirmation of previous studies, levels of circulating IFN were lower after injection of fibroblast IFN than after injection of leukocyte IFN. Despite this difference in pharmacokinetics, the natural killer activity of circulating lymphocytes was enhanced with both IFNs. Levels of DEA were not influenced by the IFN injections. Leukocyte but not fibroblast IFN caused an increase in serum levels of beta 2-microglobulin in the circulation. A similar difference between leukocyte and fibroblast IFN in their ability to influence the beta 2-microglubulin system was observed in experiments on cell cultures. Only leukocyte IFN was able to cause release of beta 2-microglobulin by either leukocytes or fibroblasts.

Effect of various interferons on the spontaneous cytotoxicity exerted by lymphocytes from normal and tumor-bearing patients.

Natural killer cell activity, which represents the spontaneous cytotoxicity of lymphocytes toward tumor cells, has been measured in 173 tumor-bearing patients and 25 healthy volunteers; no significant difference was found in mean natural killer cell activity between the two groups. The parameters of interferon-induced activation of natural killer cells were studied in order to provide a suitable test for monitoring the effect of interferon in clinical trials. The three interferons tested (leukocyte, lymphoblastoid, and fibroblast) were equally active in inducing spontaneous cytotoxicity of lymphocytes from all healthy individuals and tumor-bearing patients studied. Incubation for one hr with 100 units of interferon was sufficient to increase spontaneous cytotoxicity activity, the maximum effect being obtained when lymphocytes were incubated with 1000 units of any of the interferons used. This effect was blocked with the appropriate antiinterferon sera. The target cells for interferon seem to be positive Fc gamma receptor lymphocytes.