High Dosage Metolazone in Chronic Renal Failure

Metolazone is a modified quinazolinesulphonamide and in a dose of between 4 and 7·5 mg is an effective diuretic in man with normal renal function. Fourteen patients with non-oedematous stable chronic renal failure (creatinine clearance ranging from 1·2 to 12 ml/min) were given metolazone in doses ranging from 20-150 mg. A noticeable increase in urine flow and sodium excretion occurred, free water clearance increased, and there was a small but significant increase in potassium excretion. No side effects were noted.     

Growth Temperatures and Temperature Characteristics of Aeromonas

Six of the 13 Aeromonas hydrophila, 1 of 10 A. shigelloides, and none of 10 A. salmonicida were found to be psychrophiles. All of the rest of the strains were mesophiles. The mu values (temperature characteristics) could not be used to distinguish psychrophiles from mesophiles.     

Release of Envelope Glycoprotein from Rabies Virions by a Nonionic Detergent

Treatment of rabies virus with the nonionic detergent Nonidet P-40 resulted in solubilization of viral lipids and in a preferential release of the envelope glycoprotein. The other viral proteins and the viral ribonucleic acid remained associated in "core" particles sedimenting at a rate similar to that of intact virions. After fractionation of treated virus by velocity centrifugation in a sucrose density gradient, the amount of residual glycoprotein recovered in the "core" particle fraction and the extent of contamination of the glycoprotein fraction by other viral components were dependent on the ratio of detergent to viral protein used.     

Isolation and Characterization of Temperature-Sensitive Mutants of Vesicular Stomatitis Virus, New Jersey Serotype

Forty-eight temperature-sensitive (ts) mutants have been isolated from a wild-type strain of the New Jersey serotype of vesicular stomatitis virus (VSV) after exposure to the base analogue mutagen 5-fluorouracil. Of these mutants, 47 have been classified into 6 nonoverlapping complementation groups containing 21, 17, 4, 3, 2, and 1 mutant, respectively (1 mutant remaining unallocated). The ribonucleic acid (RNA) phenotype of 23 of these mutants has been established. Four of the six groups contain one or more mutants unable to synthesize detectable amounts of viral RNA under restrictive conditions (39 C). No complementation was observed in mixed infection with ts mutants from the five established complementation groups of the Indiana serotype of VSV.     

The Distribution of Crossovers along Unreplicated Lambda Bacteriophage Chromosomes

The distribution of crossovers along unreplicated chromosomes of bacteriophage lambda has been examined by determining the density distributions and genotypes of particles in the progenies of crosses of density-labeled by ordinary parents in the presence of genetic blocks to replication. The Red and Rec systems combined produce crossovers primarily near the ends (especially the right end) of the chromosome. Removal of the generalized lambda recombination functions by red and gam mutations results in loss of these terminal crossovers; coupled with this loss is a disappearance of the differential dependence of recombination frequencies in terminal and central intervals on DNA synthesis. Removal of the bacterial system by a recA mutation results in severe depression of crossing over among unreplicated phage, with the few recombinants produced by the lambda system occurring near the right end.     

Revertants and Secondary arom-2 Mutants Induced in Non-Complementing Mutants in the arom Gene Cluster of Neurospora Crassa

Extensive genetical and biochemical studies have been performed with revertants and secondary arom-2 mutants induced in two different primary non-complementing mutants which map within the arom gene cluster of Neurospora crassa. These studies indicate that mutant M54 but not M25 can revert by super-suppressor mutations in unlinked genes, thus confirming previous evidence that M54 contains a nonsense codon. At least three new super suppressors of M54 have been detected. All four super suppressors (including one previously detected) when combined with M54 result in high levels of all five of the arom enzymic activities in the form of arom multienzyme complexes very similar to (but not necessarily identical with) that in wild type (WT).-Evidence has also been obtained that the two non-complementing mutants can yield revertants which appear to result from true back mutations and produce arom aggregates essentially indistinguishable from that of WT. In addition, M25, but not M54, when plated on quinic acid yields revertants (secondary mutants) some of which are phenotypically indistinguishable from arom-2 primary mutants and others of which, although also mapping within the arom-2 gene, exhibit unusual properties. Genetic evidence indicates that the M25 secondary mutants are localized within the arom-2 gene, but that they arise from mutational events more complex than ones resulting in single base pair changes in the M25 codon.-The recovery of secondary arom-2 mutants as revertants of non-complementing arom mutants provides strong evidence, independent of earlier recombination data, that non-complementing arom mutants are located within the arom-2 structural gene of the arom gene cluster. In addition, the occurrence and characteristics of these secondary arom-2 mutants provide strong evidence, independent of the results with nonsense suppressors, that the arom gene cluster is transcribed, beginning with the arom-2 gene, as a single polycistronic messenger ribonucleic acid (mRNA) molecule which is subsequently translated into the arom multienzyme complex.     

Stability of sodium and potassium complexes of valinomycin

Stability constants of sodium and potassium complexes of valinomycin in some alcohols and water—organic solvent mixtures have been determined by titration, using circular dichroism to monitor complex formation. Constants range from 10¹ to 10⁶ M⁻¹. Stability of the potassium and sodium complexes increases with decreasing dielectric constant, but the ratio of the constants remains about 10³–10⁴. As others have shown, a similar selectivity for K⁺ is observed in a number of other types of measurements involving valinomycin. These include the permeability and conductance ratios which characterize the selectivity of cation transport through membranes and the ratio of salt extraction equilibrium constants. On the basis of data presented here, and elsewhere, it is suggested that conformational constraints within the depsipeptide part of the complexes aid ion selectivity and that differences in cation solvation and carbonyl ligand binding energies make an important, roughly equal, contribution.     

The role of adenosine 3′:5′-cyclic monophosphate in the division of WI 38 cells. The cellular response to prostaglandin E1 and the effects of an cyclic adenosine 3′:5′-cyclic monophosphate analogue and prostaglandin E1 on cell division

Inhibition of growth and DNA synthesis was observed in WI 38 cells incubated with 8-methylthioadenosine 3':5'-cyclic monophosphate or prostaglandin E(1). The effect of both compounds on cell growth was reversible. On removal of these compounds from culture media the cells initiated DNA synthesis and divided. In addition, prostaglandin E(1) stimulated cyclic AMP formation in these cells to over 40 times the normal basal value. The increase in cyclic AMP concentration in WI 38 cells after addition of prostaglandin E(1) showed a marked variation. Cells that had recently been treated with trypsin and plated at a lower cell density exhibited a smaller response to addition of prostaglandin E(1) than cells that had divided and reached confluence.