Effects of formamidoxime on macromolecular synthesis in regenerating liver and hepatomas

Formamidoxime caused an inhibition of [³H]thymidine incorporation into DNA in regenerating liver and transplanted hepatomas of different growth rates when administered by i.p. injection to rats. A dose level of formamidoxime (500 mg/kg body weight) which caused at least a 75% inhibition of DNA synthesis in these tissues had little or no effect on the incorporation of [³H]orotate into total RNA. After administration of formamidoxime there was no significant effect on amino acid nitrogen concentration in the tissues. The incorporation of ³H-labeled amino acids into acid-soluble material, cytoplasmic proteins and acid-insoluble nuclear proteins were either unaffected or showed only small changes after treatment of rats with the drug. In regenerating rat liver and Morris hepatomas 7787 and 7777, formamidoxime caused an inhibition of incorporation of ³H-labeled amino acids into both lysine-rich and arginine-rich histones. In the host livers of rats bearing the transplanted hepatomas, histone synthesis was less affected. The data indicated that formamidoxime causes inhibitory effects which are similar in nature and extent to those previously shown for the structurally related compound, hydroxyurea, in the regenerating rat liver and demonstrated that these effects can also be observed in liver tumors.     

Interactions of an antitumor platinum compound with deoxyribonucleic acid, histones, L-amino acids, poly-L-amino acids, nucleosides and nucleotides

Interaction of cis-dichloro(dipyridine)platinum(II) (cis-PPC) with calf thymus DNA, calf thymus histone, l-amino acids, poly-l-amino acids, nucleosides, and nucleotides has been evaluated by equilibrium dialysis technics. At least a 28 % decrease in the association of cis-PPC with DNA occurs when the platinum compound is pre-incubated with l-amino acids. The greatest decrease in association is seen upon pre-incubation of the platinum compound with the free amino acids. Glut, Asp, Lys, Arg, and CySH, before the addition of a sack containing a solution of DNA. The low level of association between DNA and the amino acids tends to rule out competition between cis-PPC and amino acids for DNA association sites. cis-PPC was repelled from sacks containing positively charged poly-l-Lys, poly-l-Arg, and calf thymus histone; however, in the presence of poly-l-Glut and poly-l-Asp, cis-PPC associated with these negatively charged polymers to a considerable degree. Enhanced chloride dissociation from cis-PPC was observed in the presence of all of the amino acids and the nucleotides GMP, CMP, UMP, and TMP, but not in the presence of AMP or the nucleosides rG and dG. In the presence of calf thymus histone, the association of cis-PPC with calf thymus DNA was reduced by more than 50% at histone/DNA ratios of 0.8–1.0.These data suggest that cis-PPC or cis-Pt(II) may associate with electron-rich areas of not only nucleic acids and proteins but also with body pools of free nucleotides and amino acids. The presence of positively charged histones shielding DNA strands in vivo suggests that the most probable point of platinum-DNA association would be at de-repressed areas of DNA which are undergoing RNA synthesis. The aquated form of the platinum complex may also associate with acidic proteins which appear to be involved in the positive control of RNA synthesis and, as a result, this interaction may be of pharmacological significance.     

The transport and metabolism of 14C-labelled indoleacetic acid in intact pea seedlings

Summary Part of the IAA-I- or IAA-2-¹⁴C applied at low concentrations to the apices of intact, light-grown dwarf pea seedling was transported unchanged to the root system The calculated velocity of transport in the stem was 11 mm per hour. In the root the label accumulated in the developing lateral root primordia.A large proportion of the applied IAA was converted by tissues of the apical bud, stem and root to indole-3-acetyl-aspartic acid (IAAsp). This compound was not transported. In addition evidence was obtained for the formation of IAA-protein complexes in the apex and roots, but not in the fully-expanded internodes.Large quantities of a decarboxylation product of IAA, tentatively indentified as indole-3-aldehyde (IAld), and several minor metabolites of IAA, were detected in extracts of the roots and first internodes, but not in the above-ground organs exposed to light. These compounds were readily transported through stem and root tissues. Together, the decarboxylation of IAA and the formation of IAAsp operated to maintain a relatively constant level of free IAA-¹⁴C in the root system.     

Metabolism of Glutamic Acid and N-Acetylglutamic Acid in Leaf Discs and Cell-free Extracts of Higher Plants

Radioactive glutamic acid and N-acetylglutamic acid have been incubated with normal and wilted leaf discs and radioactivity recovered in uncombined proline. The discs which had been placed under moisture stress incorporated considerably more label in uncombined proline than did normal discs.     

Properties of the inactive ribosomal components in rat liver and hepatoma

1. The relative concentrations of the inactive ribosomal components were compared in normal and regenerating rat liver and in two transplantable rat hepatomas (hepatomas 7800 and 5123D). 2. The size of the ribosomal-subunit pools in normal liver was not significantly affected by partial hepatectomy or neoplasia although, as shown previously, significant changes do occur in the monomer pool. 3. Further, the subunit pools in both liver and hepatoma were not significantly influenced by several treatments that caused dramatic changes in the size of the ribosomal monomer (and dimer) pools. 4. The high concentration of inactive monomers and dimers in the hepatomas appears to arise from limitations at the translational level, since they can be incorporated into pre-existing polyribosomes under the influence of cycloheximide.     

Pathogenesis of Lethal Shock After Intravenous Staphylococcal Enterotoxin B in Monkeys

The pathogenesis of shock in the rhesus monkey given intravenous staphylococcal enterotoxin B (SEB) is not understood. Several cardiovascular changes produced by a highly purified preparation of SEB were studied after administration of doses ranging from 50 to 1,000 mug/kg. Irreversible arterial hypotension was found consistently at the higher doses. Arterial blood pressure and cardiac output declined substantially as shock developed. Total peripheral vascular resistance did not rise at any time, but showed a significant fall during the late stages of shock. Portal and central venous pressures remained essentially unchanged. Venous O(2) content and pO(2) declined gradually throughout the period of toxemia, but arterial O(2) content remained constant until just prior to death, when a slight fall was noted in some monkeys. These changes were consistent with a pooling of blood in the peripheral vascular beds and seemed to resemble cardiovascular responses reported to occur in monkeys during shock due to bacterial endotoxin. Epinephrine, administered in the late stages of shock, caused arterial pressure to increase almost immediately and cardiac output to return to normal about 1 min later. Although life could occasionally be prolonged for several hours by continuous or intermittent epinephrine infusions, this therapy never succeeded in reversing the lethal effects of high doses of SEB.     

Observations on the Occurrence, Distribution, and Seasonal Incidence of Blue-green Algal Viruses

Phycovirus populations were found in 11 of the 12 waste stabilization ponds studied. These populations were comprised solely of blue-green algal (BGA) viruses. Two virus types were observed, one of which was related to the previously reported LPP-1 virus. The incidence and magnitude of the LPP group indicated that several of the ponds supported well-established BGA virus populations of this type. Counts as high as 270 plaque-forming units/ml were noted; however, marked differences in the nature and magnitude of these BGA viruses were apparent even in geographically related ponds of similar design. Of the algal strains found dominant in these ponds, none was of the type reported susceptible to the LPP viruses.     

Micromorphology of Cryptococcus neoformans

Fine details of the internal and external morphology of Cryptococcus neoformans as seen in ultrathin sections are described and illustrated with electron micrographs. The capsule characteristic of this species contained microfibrils (30 to 40 A in diameter) that appeared to radiate from the cell wall and to coil and intertwine in various directions. These thin, uniformly structured, electron-dense filaments are believed to represent complex polysaccharide molecules. The internal morphology of C. neoformans was in many ways similar to that of yeasts studied by other authors. The cell was uninucleate with a single nucleolus. The nuclear envelope, a pair of unit membranes interrupted by pores, was typical of that found in eucaryotic organisms. Smooth endoplasmic reticulum, mitochondria, vacuoles, storage granules, and ribosomes were consistent features of the cytoplasm. In addition, C. neoformans presented membranous organelles derived from the plasma membrane and comparable to bacterial mesosomes and mitochondria of an annulate type.