Antineoplaston A in cancer therapy. (I).

Twenty-one patients with advanced cancer or leukemia were treated with antineoplaston A and followed for up to nine months. Dosage by intravenous, intramuscular, subcutaneous, rectal, intrapleural, intravesical and/or topical administration ranged from 0.6 to 33 U/m2/24 h. Treatment was well tolerated, although side effects included fever of short duration and elevation of platelet and white blood count. In 18 cases some degree of clinical improvement was observed. Complete remission occurred in 4 cases. More than 50% remission occurred in 4 other cases which, along with another 6 cases, are continuing the treatment with high doses of antineoplaston A and show a continuing regression of the tumors although not yet achieving the criteria for complete remission; 2 of these 6 cases seem unlikely to achieve remission. Two patients temporarily discontinued treatment. During treatment, 5 patients expired; in 2 of them, however, was seen significant regression of the neoplastic process. The deaths were not due to cancer or to any toxicity incurred by the treatment.     

A novel J8 domain gene,IbJ8, inIpomoea batatas (L). Lam.

Sweet potato cDNAs that encode IbJ8, the smallest known J-domain protein, were isolated and characterized. This genome has at least two copies ofIbJ8, which is expressed preferentially in the leaves, flowers, petioles, and stems. Spatial and temporal patterns were studied at different developmental stages, and expression was greater in younger leaves than in older ones. Moreover, expression in roots that arose from single-leaf cuttings was lower at 15, 20, and 30 d than at 40 d, and then the signal was undetectable at 60 d after planting. These results suggest thatIbJ8 expression may be related to the organ age or developmental stage.     

Structure of poly d(A).poly d(T).

On the basis of the x-ray data from polycrystalline and well oriented fibers of the sodium salt of poly d(A).poly d(T) (Arnott et al, Nucl. Acids Res. 11, 4141-4155 (1983), a revised B'-DNA model incorporating B-like adenine and thymine strands is shown to give a much better x-ray agreement (R = 0.25) than the previously assigned model consisting of mixed sugar conformations in the two strands. The narrowing of the minor and the widening of the major grooves are promiscuous features of B'-DNA, which are common to all poly d(purine).poly d(pyrimidine) duplexes with two hydrogen bonded base-pairs and are in marked contrast with classical B-DNA. Due to modest propeller (-15 degrees), the cross strand diagonal hydrogen bonds (0.37 nm) in this duplex are not as strong as those in A,T-rich oligonucleotide crystal structures.     

Structure of Poly (U).poly (A).poly (U)

The molecular structure of poly (U).poly (A).poly (U) has been determined and refined using the continuous x-ray intensity data on layer lines in the diffraction pattern obtained from an oriented fiber of the RNA. The final R-value for the preferred structure is 0.24, far lower than that for the plausible alternatives. The polymer forms an 11-fold right-handed triple-helix of pitch 33.5A and each base triplet is stabilized by Crick-Watson-Hoogsteen hydrogen bonds. The ribose rings in the three strands have C3'-endo, C2'-endo and C2'-endo conformations, respectively. The helix derives additional stability through systematic interchain hydrogen bonds involving ribose hydroxyls and uracil bases. The relatively grooveless cylindrical shape of the triple-helix is consistent with the lack of lateral organization.     

Structure of poly (I).poly (A).poly (I)

The molecular structure of poly (I).poly (A).poly (I) has been determined and refined using the continuous intensity data on layer lines in the x-ray diffraction pattern obtained from an oriented fiber of this polymorphic RNA complex. The polymer forms a 12-fold right-handed triple-helix of pitch 39.7A and each base-triplet is stabilized by quasi Crick-Watson-Hoogsteen hydrogen bonds. The ribose rings in all the three strands have C3'-endo conformations. The final R-value for this best structure is 0.24 and the x-ray fit is significantly superior to all the alternative structures where the different chains might have different furanose conformations. This all-purine triple-helix, counter-intuitively, has a diameter roughly 3A shorter than that of DNA and RNA triple-helices containing a homopurine and two complementary homopyrimidine strands. Its compact, grooveless cylindrical shape is consistent with the lack of lateral organization.