The hemodynamic destruction of circulating cancer cells

The blood-stream is the major disseminative route for metastasizing cancer cells, and metastases are generated when the cancer "microemboli" are trapped in the microcirculation. However, most circulating cancer cells are rapidly destroyed shortly before and/or after arrest. Traditionally, destruction is attributed to the cellular or humoral response of the host defense systems. A novel, non-exclusive mechanism for cancer cell destruction has been proposed by Weiss and Dimitrov in which friction or adhesion between circulating cancer cells and capillary walls causes local vascular blockage, and the blood-pressure differentials normally existing over the entire length of a capillary are consequently applied over the length of the cancer cell. In a simple model, this pressure differential is expected to cause expansion of the cancer cell membrane, resulting in increases in tension above a critical level, with consequent membrane rupture and cell death. In vivo and in vitro experimental tests of this hypothesis are outlined.     

Behavioral endocrinology of male rats with periodic sexual contacts with exclusive or varied females

Sexual contact keys a profound series of acute and chronic changes in males that, presumably, are orchestrated by acute pulsatile release of hormones. An experimental paradigm is reported in which male rats were paired periodically with either the same or different estrous females to receive identical amounts of copulatory experiences. Results confirmed the hypothesis that exposure to an unfamiliar female would induce a different endocrine response which would be reflected in various androgen-sensitive systems. The "successively polygynous" males showed more sexual behavior than "monogamous" males, and their respective females solicited the males differently, as well. Circulating levels of testosterone were higher immediately after sexual contact with an unfamiliar than with a familiar female partner. There were no differences in testosterone titers among the groups when the animals were killed at either 2 or 7 weeks after the final copulatory experiences. Yet, necropsies at 2 weeks postcopulation revealed that primary and secondary sex structures from polygynous males clearly were larger. Differences between the two experimental groups were reduced after 7 weeks of sexual rest, yet, polygnous males continued to show a different structural profile than the other groups. Conclusions were that males may experience greater activation of androgen-sensitive behavior and physiology following qualitatively different sexual contacts.     

Effect of selection intensity and population size on percent oil in maize,Zea mays L

Summary The effect of selection intensity and population size on the response to selection for percent oil in the grain of maize (Zea mays L.) was evaluated in a replicated experiment over ten cycles of selection. An open-pollinated variety, Armel's Reid Yellow Dent, was divided into subpopulations of 6,10 and 50 plants. Selection proportions of 17% and 5% were imposed upon each subpopulation. Selection was based on the percentage of oil in individual kernels as determined by wide-line nuclear magnetic resonance spectroscopy. As expected, total response to selection increased with larger population sizes and selection intensities. The concave shape of the response curves suggested that an appreciable part of the genetic variance can be attributed to additive genes at high initial frequencies, dominance genes at low initial frequencies, or to the generation of negative linkage disequilibrium due to selection. The consistently greater loss of vigor experienced by the more intensely selected populations reflects the enhancement of inbreeding due to artificial selection, an effect that increases with the intensity of selection. The results indicate that combined selection, based on kernels and using within- and amongfamily information, will be more efficient than other conventional selection procedures, including the normal combined scheme where selection is based on plants.Deceased     

Allelic variation in HLA-B and HLA-C sequences and the evolution of the HLA-B alleles

Several new HLA-B (B8, B51, Bw62)- and HLA-C (Cw6, Cw7)-specific genes were isolated either as genomic cosmid or cDNA clones to study the diversity of HLA antigens. The allele specificities were identified by sequence analysis in comparison with published HLA-B and -C sequences, by transfection experiments, and Southern and northern blot analysis using oligonucleotide probes. Comparison of the classical HLA-A, -B, and -C sequences reveals that allele-specific substitutions seem to be rare events. HLA-B51 codes only for one allelespecific residue: arginine at position 81 located on the 1 helix, pointing toward the antigen binding site. HLA-B8 contains an acidic substitution in amino acid position 9 on the first central sheet which might affect antigen binding capacity, perhaps in combination with the rare replacement at position 67 (F) on the ul helix. HLA-B8 shows greatest homology to HLA-Bw42, -Bw41, -B7, and-Bw60 antigens, all of which lack the conserved restriction sites Pst I at position 180 and Sac I at position 131. Both sites associated with amino acid replacements seem to be genetic markers of an evolutionary split of the HLA-B alleles, which is also observed in the leader sequences. HLA-Cw7 shows 98% sequence identity to the JY328 gene. In general, the HLA-C alleles display lower levels of variability in the highly polymorphic regions of the 1 and 2 domains, and have more distinct patterns of locus-specific residues in the transmembrane and cytoplasmic domains. Thus we propose a more recent origin for the HLA-C locus.     

Factors involved in multiplication and survival ofEscherichia coli in lake water

The population of a strain ofEscherichia coli that was resistant to nalidixic acid and streptomycin declined rapidly in samples of sterile and nonsterile Cayuga Lake water and reached an undetectable level in nonsterile water at 24 and 72 hours when counted on eosin-methylene blue (EMB) agar and half-strength trypticase soy agar (TSA), respectively. In sterile lake water amended with 10g amino acids per ml or 0.1 M phosphate,E. coli multiplied exponentially for more than 24 hours. The addition ofRhizobium leguminosarum biovarphaseoli to unamended sterile lake water prevented the decline ofE. coli, and its addition to amended sterile lake water preventedE. coli multiplication. The cell density of this strain ofE. coli declined in the first 8 hours after its introduction into an inorganic salts solution, but the bacterium then grew extensively. This increase in abundance was not observed in the presence ofR. phaseoli, andE. coli counts on half-strength TSA remained unchanged between 8 hours and 6 days. When counted on EMB agar, the abundance of the antibiotic-resistant strain ofE. coli and a strain not selected for resistance increased in solutions containing phosphate and amino acids but declined in the presence of high densities ofR. phaseoli. Many of the cells of the antibiotic-resistantE. coli strain failed to grow on antibiotic-amended EMB agar after introduction of the organism into nonsterile or sterile lake water or into an inorganic salts solution containingR. phaseoli, although colonies appeared on TSA. The data suggest thatE. coli cells grown on rich media suffer a shock when introduced into lake water because of low hypotonicity, the indigenous competing flora, or both. This shock is prevented by either phosphate buffer or by amino acids at low concentration. The shocked bacteria formed colonies on half-strength TSA. Depending on environmental conditions, the presence of a second organism either has no effect or results in an increase or decrease inE. coli numbers.     

Oncogene cooperation in lymphocyte transformation: malignant conversion of E mu-myc transgenic pre-B cells in vitro is enhanced by v-H-ras or v-raf but not v-abl.

Although transgenic mice bearing a c-myc gene controlled by the immunoglobulin heavy-chain enhancer (E mu) eventually develop B-lymphoid tumors, B-lineage cells from preneoplastic bone marrow express the transgene but do not grow autonomously or produce tumors in mice. To determine whether other oncogenes can cooperate with myc to transform B-lineage cells, we compared the in vitro growth and tumorigenicity of normal and E mu-myc bone marrow cells infected with retroviruses bearing the v-H-ras, v-raf, or v-abl oncogene. The v-H-ras and v-raf viruses both generated a rapid polyclonal expansion of E mu-myc pre-B bone marrow cells in liquid culture and 10- to 100-fold more pre-B lymphoid colonies than normal in soft agar. The infected transgenic cells were autonomous, cloned efficiently in agar, and grew as tumors in nude mice. While many pre-B cells from normal marrow could also be induced to proliferate by the v-raf virus, these cells required a stromal feeder layer, did not clone in agar, and were not malignant. Most normal cells stimulated to grow by v-H-ras also cloned poorly in agar, and only rare cells were tumorigenic. With the v-abl virus, no more cells were transformed from E mu-myc than normal marrow and the proportion of tumorigenic pre-B clones was not elevated. These results suggest that both v-H-ras and v-raf, but apparently not v-abl, collaborate with constitutive myc expression to promote autonomous proliferation and tumorigenicity of pre-B lymphoid cells.     

Reduced neuroexcitatory effect of domoic acid following mossy fiber denervation of the rat dorsal hippocampus: further evidence that toxicity of domoic acid involves kainate receptor activation

Domoic acid, an excitatory amino acid structurally related to kainic acid, has been shown to be responsible for the severe intoxication presented, in 1987, by more than one hundred and fifty people having eaten mussels grown in Prince Edward Island (Canada). Unitary extracellular recordings were obtained from pyramidal neurons of the CA3 region of the rat dorsal hippocampus. The excitatory effects of microiontophoretic applications of domoic acid and of the agonists of the two other subtypes of glutamatergic receptors, quisqualate and N-methyl-D-aspartate, were compared on intact and colchicine-lesioned sides. Similar to what has been previously found for kainate, the colchicine lesion of the mossy fiber projections induced a 95% decrease of the neuronal responsiveness to domoic acid, whereas the effect of quisqualate was unchanged and that of N-methyl-D-aspartate was only slightly decreased. These results provide further electrophysiological evidence that domoic acid is a potent agonist of kainate receptors and that it may produce its neuroexcitatory and neurotoxic effects, in the hippocampal CA3 region, through activation of kainate receptors located on the mossy fiber terminals.