Chemoprevention clinical trials.

As part of a program to develop drugs which will delay or prevent cancer in humans, the Chemoprevention Branch, National Cancer Institute, National Institutes of Health, is sponsoring 12 Phase I and 22 Phase II and III clinical trials. Three agent classes are significantly advanced in the trials. These are the retinoids, including 13-cis-retinoic acid, retinol, and 4-hydroxyphenylretinamide (nine studies), beta-carotene (seven studies), and calcium compounds (three studies). In addition, six promising new compounds are in Phase I or Phase II trials. These are: piroxicam, ibuprofen, oltipraz (a dithiolthione), difluoromethylornithine, glycyrrhetinic acid, and N-acetylcysteine. Key concepts related to the development of cancer chemopreventive agents are (1) the need for long-term administration, (2) the need for oral route of administration, (3) the matching of toxic side effects to degree of cancer risk.     

Cysteine sulfinic acid decarboxylase activity in response to thyroid hormone administration in rats

The modulation of hepatic and renal cysteine sulfinic acid decarboxylase (EC 4.1.1.29) activities by triiodothyronine (T3) was studied in a series of experiments. In a dose--response study, hepatic cysteine sulfinic acid decarboxylase activity (CSAD) was depressed by 65% and renal activity was increased threefold in rats injected with 100 micrograms T3/100 g body wt for 7 days when compared to rats injected with 0.3 micrograms T3/100 g body wt. Western blot analysis indicated that these changes in CSAD activity were due to changes in the quantity of CSAD protein. Changes in hepatic and renal activities were not evident until 24 h after T3 administration. In response to T3 clearance, hepatic and renal CSAD activities approached euthyroid values 4-7 days after cessation of T3 injections although serum T3 concentrations were no different from euthyroid values 48 h after T3 injections were stopped. These data indicate that thyroid hormone effects persist after T3 clearance. The response of CSAD to thyroid status may be related to its role in taurine biosynthesis.     

Marine ecosystem dynamics: Comparison of scales

When marine and terrestrial ecological systems are compared at the same time scales, there are very great differences in their relations with their physical environments. Similarities arise when comparisons are made at different time scales. There are significant consequences for management.     

Distribution of Legionella longbeachae serogroup 1 and other legionellae in potting soils in Australia.

Legionella longbeachae serogroup 1 and other Legionella spp. were isolated from 73% of 45 potting soils made in Australia by 13 manufacturers but were not detected in 19 potting soils made in Greece, Switzerland, and the United Kingdom examined between March 1989 and May 1990. Several Legionella species were isolated from a small number of samples of uncomposted pine sawdusts, but it is not known whether sawdust was the source of some of the legionellae found in potting soils. Legionella spp. persisted for periods ranging from 3 to 10 months in a potting soil held at temperatures between -20 and 35 degrees C. Isolates of L. longbeachae serogroup 1 from soil did not grow at 43 degrees C, a temperature which was also lethal for this species in soil. Most Legionella spp. isolated from potting and natural soils belonged to one distinct group according to analysis of ubiquinones and were serologically related to several known species in this group. A small number of potting soils contained L. pneumophila and L. micdadei.     

Host-Parasite Interaction of Resistant Sugarbeet and Heterodera schachtii

The host-parasite relationships between Heterodera schachtii Schm. and the nematode-resistant diploid Beta vulgaris L. line ''51501'' were examined via serial sections of secondary rootlets. Second-stage larvae penetrated sugarbeet roots and migrated up to 1.95 mm before establishing permanent feeding sites. Most sedentary larvae were oriented parallel to the root axis or in various diagonal or folded positions in the cortex. Nematodes adopted no definite orientation with regard to the root apex. Nematode feeding stimulated formation of multinucleate syncytia in host tissues. Syncytia were 0.3-1.1 mm in length, up to 90 [mu]m × 150 [mu]m in cross section. Root diameters were enlarged close to feeding sites. Usually nematodes deteriorated concomitant with necrosis of syncytia, and dead nematodes frequently appeared macerated or flattened and deformed. Most nematodes did not develop to maturity" in the resistant host tissues, Cavities left by collapse of syncytia were filled by growth of parenchymatous tissue.     

Specificity of Insertion by the Translocatable Tetracycline-Resistance Element Tn10

Genetic analysis of 131 independent transpositions of the tetracycline-resistance element Tn10 from a single site in phage P22 into the histidine operon of Salmonella typhimurium reveals that Tn10 insertions are not randomly distributed along this chromosomal target. The insertions occur in 22 different "clusters"; insertions within each cluster are very tightly linked in recombination tests. Tn10 insertions are not evenly distributed among the identified clusters. The existence of these clusters suggests that this chromosomal target contains particular genetic signals that guide Tn10 to particular preferred positions for insertion. Insertions within each cluster occur in both orientations with roughly equal frequency.--The relationship among different insertions within each cluster has been examined. The resolution of genetic mapping places an upper limit of about 50 basepairs on the distance between different insertions within a cluster. Different insertions within a cluster usually have the same reversion frequency; however, heterogeneity in reversion frequency has been detected in at least two clusters. For most clusters, the available data are consistent with the simple possibility that all insertions within a cluster are at identical positions; however, the data do not exclude other possibilities.     

Absence of cytosine methylation at C-C-G-G and G-C-G-C sites in the rDNA coding regions and intervening sequences of Drosophila and the rDNA of other insects.

Cytosine residues in C-G dinucleotides are frequently methylated in eukaryote DNA. In DNA of the dinoflagellate C. cohnii, the sequence C-MeC-G-G apparently renders Hpa II (C-C-G-G) incapable of digesting whole cell DNA in general, and rDNA in particular. Msp I, which also recognizes C-C-G-G but cleaves irrespective of methylation, degrades C. cohnii DNA and produces rDNA segments of 10.2 to 1.4 kb. We have applied this Hpa II/Msp I test to unfractionated DNA, and to rDNA and the rDNA intervening sequence of Drosophila virilis embryos and adults. There is no evidence of C-MeC-G-G sequences in either developmental stage of this species. Absence of G-MeC-G-C from coding and intervening sequences of rDNA was shown in comparisons of Hha I (G-C-G-C) cleavage patterns of unfractionated DNA and cloned (unmodified) segments of rDNA. Comparisons of Hpa II and Msp I cleavage products of DNA from the house fly, the flesh fly and a bumblebee also revealed no internal cytosine methylation in the sequence C-C-G-G. Because amounts of McC in C-G dinucleotides vary greatly among species, from apparent nonexistence to substantial proportions, no inference may yet be drawn about the role of such base modifications in DNA.     

Peroxide induced chemiluminescence in an in vitro proline hydroxylation system.

This communication describes a hydrogen peroxide (HOOH) induced chemiluminescence (CL) in an in vitro aromatic (proline) hydroxylation system. The reactive components of the system are ascorbic (AA), ethylene diamine tetraacetic disodium salt (EDTA), ferrous sulfate, and HOOH. The CL is (1) nearly dissipated within three minutes, (2) enhanced and/or sustained by proline and polylysine to a greater degree than by alanine, (3) partially inhibited by a,a' dipyridyl, EDTA, and ethanol, (4) most dependent upon the presence of Fe2+, AA, and HOOH. The in vitro proline hydroxylation system is more effective than ground state oxygen in terms of the CL produced and the percent of hydroxyproline formed.