John Hobbs

Intravascular lipoleiomyomatosis: A report of two cases

Two cases of intravascular leiomyomatosis (IVL) with histologic features of a lipoleiomyoma (LPL) are reported. Both tumors arose from preexisting uterine leiomyomata. One tumor was found incidentally in a uterus removed for leiomyomata. The other tumor extended up the inferior vena cava into the right side of the heart and presented as a cardiac mass. Although LPL is considered to be a benign lesion, IVL recurs in approximately 10% of reported cases, and must be distinguished from low-grade endometrial stromal sarcoma and leiomyosarcoma with vascular invasion. The combination of features in these cases lends support to the theory that IVL may arise by intravascular extension of a preexisting leiomyoma.

Poly 2'-deoxy-2'-aminouridylic acid.

Abstract The synthesis of poly 2′-deoxy-2′-aminouridylic acid is described. This analog of poly rU does not seem to form a double stranded complex with the complementary poly rA under normal conditions.

Poly 2'-deoxy-2'-chlorouridylic and -cytidylic acids.

A large number of polynucleotides with modified purine and pyrimidine bases has been prepared and the influence of such modifications on the formation and stability of double helices has been studied [l] . Although it is well documented that the thermal stability of double helices is also determined by the nature of the sugar residue of the nucleotide [2] , so far very few studies have been undertaken to examine this effect by modification of the sugar. The properties of poly 2’-0methyladenylic acid were investigated by Bobst et al. [3] and those of poly 2’-O-methylcytidylic and poly 2’-O-methyluridylic acids respectively by Zmudzka et al. [4,5]. In an attempt to widen our understanding of the factors determining thermal stability of double helices we have investigated some properties of poly 2’-deoxy-2’chlorouridylic acid and poly 2’-deoxy_2’-chlorocytidylic acid.

The antiviral activity of certain thiophosphate and 2'-chloro substituted polynucleotide homopolymer duplexes.

Abstract Poly(rI)·poly(rsC) (polyriboinosinic acid) (polythiophosphate ribocytidylic acid) was found to be a slightly less potent interferon inducer than poly(rI)·poly(rC). The rate of degradation for poly(rI)·poly(rsC) and poly(rI)·poly(rC) by serum nucleases also proved to be very similar. In contrast, substitution of the 2′-hydroxyl by a chlorine atom in poly(rU) (polyribouridylic acid) and poly(rC) greatly increased their resistance to serum nucleases. Poly(rA)·poly(2′-ClU) (polyriboadenylic acid) (poly2′-chlorouridylic acid) and poly(rI)·poly(2′-ClC) were incapable of producing interferon although they possessed as great or greater thermal stability and much greater nucleolytic resistance than the unsubstituted interferon producing duplexes. This lack of interferon production by the 2′-Cl duplexes could not be explained by the failure of human foreskin fibroblasts (HFF) to take up these polymers. In addition, poly(rI)·poly(2′-ClC) did not compete with the interfering activity or the cellular association of poly(rI)·poly(rC). Substitution of the 2′ue5f8OH by a 2′ue5f8NH2 in poly(rU) also produced a polymer incapable of producing interferon.

Anti-complement activity of polynucleotides

Abstract A biologic assay system, based on complement (C′) inhibition, is described to unravel structural differences among polynucleotides. The C′ system appears particularly suitable to distinguish (1) homo- from copoly-ribonucleotides, (2) deoxyribo- from 2′-OH and other 2′-modified polynucleotides, and (3) single homopolynucleotides from double- or triple-stranded complexes. From these studies a number of polynucleotides emerged with potent anti-C′ activities, worthy of further investigation. The most active polymers were (G) n (polyguanylic acid), (dCc1) n [poly(2′-chloro-2′deoxycytidylic acid)] and (dUz) n [poly(2′-azido-2′-deoxyuridylic acid)].

[32] The active site of ribonucleoside diphosphate reductase

Publisher Summary Ribonucleotide reductase of Escherichia coli, which catalyzes the reduction of ribonucleoside 5-diphosphates to 2-deoxynucleoside 5-diphosphates, consists of two nonidentical subunits, proteins B1 and B2. In the presence of Mg 2+, the two subunits form a 1:1 complex of active enzyme. When separated, neither subunit has any known biological activity. Protein B1 that has a molecular weight of 160,000 contains the active dithiols, and is capable of interacting with thioredoxin, and contains binding sites both for the ribonucleoside diphosphate substrates and for the nucleoside triphosphate effectors. Protein B2 has a molecular weight of 78,000 and contains bound nonheme iron and an organic free radical essential for activity. The radical gives rise to a characteristic light absorption at 410 nm. B2 is inactivated by removal of the iron or by destruction of the radical with hydroxylamine. No binding of substrates or effectors to B2 can be demonstrated. The inactivation of ribonucleotide reductase by 2t-deoxy-2 -chlorocytidine and by 2P-deoxy-2 - chlorouridine 5-diphosphate, as well as by 2-deoxy-2-azidocytidine 5-diphosphate, is described in the chapter. The results indicate that both B1 and B2 contribute to the active site of the enzyme and that the radical present in B2 directly participates in the atalytic process together with the redox active dithiols of B1.