Hypothalamic amenorrhea in runners of normal body composition

Three amenorrheic runners of normal body weight, in whom organic disease had been excluded, were found to exhibit: (1) normal body composition, (2) low baseline concentrations of serum LH and normal concentrations of FSH, (3) normal to hyper-responsiveness of LH and FSH to GnRH testing, and (4) normal and possibly increased frequency of LH pulsations. In one of the 3 runners, the administration of naloxone was followed by a pronounced increase in the amplitude of the LH pulsations.     

tRNA-rRNA sequence homologies: evidence for an ancient modular format shared by tRNAs and rRNAs

Homologies between tRNAs and rRNAs are identified in searches using various combinations of Escherichia coli, yeast, Halobacterium volcanii and bovine mitochondrial sequences. As in previously reported comparisons, the homologies are too frequent and long to be attributed to coincidence, and similar frequencies from inter- and intraspecies comparisons preclude evolutionary convergence as an explanation. In contrast to the earlier studies, patterns in the positioning of the homologies are now described. Graphing the positions of the homologies along orthogonal axes that represent numbers of bases in tRNA and rRNA shows recurring patterns in the alignments. Preferred spacings of integral multiples of 9 bases are found, suggesting a periodicity in the ancestral structure from which the tRNAs and rRNAs were derived. The periodicity also suggests persistence of a modular format in both classes of molecules that survived changes in sequence that occurred during evolution. A model is proposed for the generation of the ancestral molecule and the early evolution of the coding mechanism. Elongation by self-priming and self-templating gave a hairpin with a 9 base stem. Two additional cycles gave a 70-80 base tRNA-like structure. Additional cycles yielded a tandem repeat of this unit, roughly equivalent in size to the combined rRNAs of prokaryotes. The larger RNA would contain the information and materials for generating the smaller RNAs. It is proposed that multiple recombination among such molecules gave composite structures, presumed progenitors of today's t- and rRNAs. The distribution of the conserved domains among today's species argues for the existence of the ancestral molecule prior to divergence of lines leading to the various kingdoms. Their presence in the different nucleic acids suggests the existence of a nucleic acid with multiple functions prior to partitioning of these functions among the nucleic acids that exist today. The occurrence of overlaps, overlays and consensus alignments among the homologies provides the means for identifying contiguous and neighboring conserved regions and holds promise for the reconstruction of the sequence of an ancestral molecule.     

Mode of Action of Antirheumatic Drugs

The concentrations of free and protein-bound L-tryptophan were measured in sera from normal subjects, patients with rheumatoid arthritis, pregnant women, and patients with jaundice. In the patients with rheumatoid arthritis receiving treatment with one or more antirheumatic drugs the percentage of the amino-acid bound to the circulating proteins was significantly depressed and in one patient returned to normal when therapy was stopped. Pregnancy and jaundice were also associated with raised free tryptophan and decreased bound tryptophan concentrations and bilirubin displaced the amino-acid from its binding sites on human serum proteins in vitro. It is suggested the behaviour of tryptophan mimics that of certain peptides which protect susceptible tissues against chronic inflammatory insults.     

Sexual specialization and inbreeding avoidance in the evolution of dioecy

Dioecy has evolved independently, many times, among unrelated taxa. It also appears to have evolved along two contrasting pathways: (1) from hermaphroditism via monoecy to dioecy and (2) from hermaphroditism via gynodioecy to dioecy. Most dioecious plants have close cosexual relatives with some means of promoting outcrossing (e.g., herkogamy, dichogamy, self-incompatibility, or monoecy). To the extent that these devices prevent inbreeding, the evolution of dioecy in these species cannot logically be attributed to selection for outcrossing. In these cases, the evolution of dioecy is, we believe, due to selection for sexual specialization. However, in other species, that lack outbreeding close relatives, dioecy may have evolved from gynodioecy (males and hermaphrodites) as an outbreeding device. Subsequent disruptive selection and selection for sexual specialization may have also shaped the evolution of dioecy from gynodioecy in these species, resulting in two genetically determined, constant sex morphs. Both pathways for the evolution of dioecy require the operation of disruptive selection, though the gynodioecy route involves more restrictive disruptive selection and a genetic designation of gender. In contrast, the monoecy route is not dependent on the genetic designation of two sex morphs, but, rather, allows the possibility of sexual intermediates and sexual lability. Both pathways produce one morph in which maleness is suppressed and another in which the female function is negligible or nonexistent—the reproductive mode recognized as dioecy. Evidence is presented here to support the thesis that instances of sexual lability, the presence of an array of sexual intermediates, sex-switching, and sexual niche segregation can be explained in terms of the pathway that was taken in the evolution of a particular dioecious species. In addition, the degree of sexual dimorphism seen in dioecious species is correlated with mode of pollination (insector wind-pollinated) and other ecological factors.     

Sequence requirements for the stimulation of gene amplification by a mammalian genomic element

HSAG-1 is a 3.4-kb genomic element from a human chronic lymphocytic leukemia--Chinese hamster ovary (CHO) hybrid cell line shown to stimulate the amplification of expression vectors in cis when transfected into a variety of cell lines [McArthur and Stanners, J. Biol. Chem. 266 (1991) 6000-6005]. Subfragments of HSAG-1 were tested for amplification activity by insertion into the vector, pSV2DHFR. The results suggest that multiple positive- and negative-acting elements were present that influenced amplification activity. The deletion of regions believed to contain positive-acting elements decreased or abolished the amplification stimulatory activity of the most active 1.45-kb fragment, supporting this hypothesis. The construction of composite sequences containing multiple positive elements and lacking negative elements, however, failed to enhance the activity; maximum activity was obtained only with the original intact configuration of elements. Two of two CHO HSAG-1-like elements tested had an activity equivalent to HSAG-1, while one of 24 random CHO genomic fragments tested had an activity as high as HSAG-1. The combination of sequence and structural features needed to affect the frequency of gene amplification may therefore be quite common in the mammalian genome.