1,25-Dihydroxyvitamin D3 enhances the growth of tumors in athymic mice inoculated with receptor rich osteosarcoma cells

We tested the influence of daily subcutaneous injections of 12.5 and 25 pmol of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the growth of tumors arising from intracutaneous inoculations of athymic nude mice with rat osteogenic sarcoma cells (ROS) and human melanoma cells. Both doses of 1,25(OH)2D3 increased plasma calcium levels after 3 weeks and produced a striking enhancement in tumor weight when the mice received 1,25(OH)2D3 receptor-rich ROS17/2.8 cells. In contrast, 1,25(OH)2D3 caused no consistent effect on tumor weight in mice given G-361 melanoma cells with low receptor copy number or receptor deficient ROS 24/1 cells. Thus, 1,25(OH)2D3 stimulated tumor growth in a receptor dependent fashion, in vivo, instead of inhibiting it as predicted from the reduction of proliferation of cultured cells in the presence of 1,25(OH)2D3.     

Echolocation sounds and hearing of the greater Japanese horseshoe bat (Rhinolophus ferrumequinum nippon)

Summary The relationship between the orientation sounds and hearing sensitivity in the greater Japanese horseshoe bat,Rhinolophus ferrumequinum nippon was studied.An orientation pulse consisted of a constant frequency (CF) component followed by a short downward frequency-modulated (FM) component. Sometimes, an initial upward FM component preceded the CF component. Duration of pulses was about 30 ms and the CF of resting pulses (RF) averaged 65.5 kHz. The best frequency (BF) at the lowest threshold in audiograms as measured by the pinna reflex averaged 66.1 kHz. Audiograms showed remarkable sharp cut-offs on both sides near the BF. The frequency difference between the BF and the RF was about 0.6 kHz, and the RF was always below the BF. The values of RF and BF were characteristically different from those of the European subspecies,Rhinolophus ferrumequinum ferrumequinum.Abbreviations BF best frequency - CF constant frequency - FM frequency modulated - RF resting frequency     

Quantitative structure-activity relationships of structurally similar odorless and odoriferous benzenoid musks

To reveal the difference of molecular property between structurallysimilar odorless and odoriferous musk compounds, 10 pairs ofbenzenoids (monocyclic-, dicyclic- and tricyclic-) were examined.Molecular structures of all compounds were optimized by MNDO(modified neglect of diatomic differential overlap) consideringconformation. Parameters effective in discriminating two groups,group A of 10 odorless compounds and group B of 10 musk odorcompounds, were searched from 34 candidate parameters by adaptiveleast squares. The best three parameters found were log P value(octanol/water partition coefficient), the longest side lengthof hexahedron circumscribing a molecule, and the parameter whichexpresses structural hindrance to the functional group whena molecule approaches the receptor site. The two groups of compoundswere completely discriminated using these three parameters.     

Induction of metallothionein synthesis in Menkes' and normal lymphoblastoid cells is controlled by the level of intracellular copper

A study was carried out on the uptake of copper, zinc, or cadmium ions and their induction of metallothionein synthesis in Menkes' and normal lymphoblastoid cells. The main difference between Menkes' and normal cells in the uptake of these metal ions was an increased uptake of copper ions in Menkes' cells at a low concentration of CuCl2 (2.1 microM). The CuCl2 concentration necessary to induce metallothionein synthesis in Menkes' cells was 50 microM, whereas that in normal cells was about 200 microM. The levels of zinc or cadmium ions needed to induce metallothionein in Menkes' cells were similar to those in normal cells. At least four isomers of metallothionein were induced by copper, zinc, and cadmium ions in both types of cells. Metallothionein synthesis in Menkes' and normal cells was induced when the amounts of intracellular copper reached a threshold level of approximately 0.2 nmol/10(6) cells, and the rate of metallothionein synthesis in these cells was increased as a function of the amounts of intracellular copper (0.2-1.7 nmol/10(6) cells). These results indicate that the induction of metallothionein synthesis in lymphoblastoid cells is controlled by the level of intracellular copper, suggesting that the major defect in Menkes' cells is not due to the abnormal regulation of metallothionein synthesis but to an alteration of the copper metabolism in cells by which the levels of intracellular copper become larger than those in normal cells and just lower than the threshold level for induction of metallothionein synthesis.     

Synthesis of Proteins Enriched in Li+- Induced Vegetalized Embryos of Sea Urchin during Early Development

Sea urchin embryos were vegetalized by a pulse treatment with 60 mM Li⁺ between 2.5 hr and 6 hr after fertilization at 20°C. Normal and Li⁺ -treated embryos were exposed to [³⁵S]-methionine for 2 hr at various stages and [³⁵S]-labeled proteins were analyzed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). On fluorograph of 2D-PAGE at the pre-hatching blastula stage, significant difference of labeled proteins between normal and vegetalized embryos was not observed in the range from neutral to acidic pH, but pls of several proteins were found to be shifted toward alkaline pH. At the mesechyme blastula stage, five major proteins [M.W. 36 K, 43 K (two species), 71 K and 150 K] were enriched in Li⁺-treated embryos among a few hundreds of synthesized proteins. At the late gastrula stage, the labeling intensities of these proteins except for one of 43 K proteins increased remarkably in Li⁺-treated embryos. Furthermore, two proteins (M.W. 105 K and 135 K) were also enriched in Li⁺-treated embryos at this stage. At the prism stage, these proteins enriched in Li⁺-treated embryos became hardly detectable, and the synthesis of at least four proteins (M.W. about 20 K, 41 K, 43 K and 200 K<) appeared to increase in normal embryos, but not in Li⁺-treated embryos. Synthesis of proteins eniched in Li⁺-treated embryos probably support endodermal cell differentiation.     

Synthesis of Collagen-Like Proteins in Embryonic Organs of the Sea Urchin, Hemicentrotus pulcherrimus

In sea urchin embryos exposed to ¹⁴C-proline at 20°C for 3 hr at the gastrula, prism or pluteus stage, ¹⁴C-radioactivity was found in hot acid-extractable proteins, in which more than 4% of the radioactivity was detectable in hydroxyproline residues. In these embryos, ¹⁴C-radioactivity in collagen-like proteins was found in the archenteron, spicule and embryo-wall cells. The rate of synthesis of collagen-like proteins was highest in the archenteron in the mid-gastrula stage, in the embryo-wall cells in the prism stage and in the spicule in the pluteus stage. The rate of synthesis decreased in the archenteron and increased in embryo-wall cells in the period between the mid- and late-gastrula stages, when the rate of synthesis in the spicule was quite low. Thereafter, the rate decreased slightly in the embryo-wall cells, was maintained in archenteron and increased markedly in the spicule. The rates of synthesis of collagen-like proteins are high in these embryonic organs at stages at which development and growth respectively, occur in embryos. Therefore, synthesis of collagen-like proteins probably supports morphogenesis in these embryonic organs.     

Electrogenic responses elicited by transmembrane depolarizing current in aerated body wall muscles ofDrosophila melanogaster larvae

Summary Electrical excitability of the longitudinal ventrolateral body wall muscle of the third instar larva ofDrosophila melanogaster was demonstrated. This is in contrast to previous papers which have reported that this muscle is electrically inexcitable. It was found that an air supply to the muscle through the tracheoles is essential for maintaining its excitability. In an aerated preparation, the muscle maintained a resting potential of around –80 mV for more than 1.5 h, while a nonaerated muscle depolarized to about –30 mV within 30 min. Muscles with resting potentials larger than –70 mV showed graded regenerative potentials with a double-peaked configuration in response to transmembrane depolarizing current. A tetrodotoxin- (TTX-)sensitive, voltage-dependent inward sodium current, and a tetraethylammonium-(TEA-)sensitive, voltage-dependent outward potassium current were found to be responsible for the first peak of the electrogenic response of this muscle. The rising phase of the second peak was caused by a cobalt/manganese-sensitive, voltage-dependent inward calcium current that had a threshold level near –40 mV. Elimination by TEA or barium of the delayed rectification following the first peak caused the second peak to be triggered at a lower threshold. The second peak was profoundly elongated by barium, and this effect was antagonized by external calcium. Thus, the falling phase of the second peak was most likely driven by a calcium-dependent, outward potassium current.     

UDP-GalNAc : GalNAc-mucin α-N-acetylgalactosamine transferase activity in human intestinal cancerous tissues

GalNAc transferase activities of 6 human intestinal cancerous tissues were examined using bovine submaxillary gland mucin and its desialylated derivative, asialomucin, as acceptors. A Triton X-100 extract of these tissues was used as an enzyme source. All the tissues examined had GalNAc transferase that catalyzes the transfer of GalNAc from UDP-GalNAc to serine or threonine residues of the polypeptide chain. One of 6 specimens showed in addition UDP-GalNAc:GalNAc-mucin α-GalNAc transferase activity, synthesizing a disaccharide unit, GalNAcα→ GalNAc, when asialomucin was used as an acceptor. This carbohydrate structure was deduced on the basis of results of gel filtration, exoglycosidase digestion, and high-voltage paper electrophoresis.GalNAc transferaseHuman intestinal cancerous tissueBovine submaxillary gland mucin O-Glycosidically linked sugar chain