Substituted piperidin-2-one biphenyltetrazoles as angiotensin II antagonists

A novel series of substituted piperidine-2-ones has been identified as antagonists of angiotensin II. These compounds showed high affinity for the receptor in bovine adrenal cortex binding assays with IC₅₀'s as low as 20nM. They are potent inhibitors of angiotensin II induced contractions in rabbit aortic rings, with pA₂ values as high as 9. A number of these compounds are also orally active as antihypertensives in spontaneously hypertensive rat preparations.     

UK-73,093: A non-peptide neurotensin receptor antagonist

UK-73,093 was identified in a screening program as a compound able to displace [³H]-neurotensin from its bovine brain receptor. We describe the discovery of this compound, species differences in receptor affinity and its characterization as a functional neurotensin antogonist in vitro and in vivo.     

Co-distribution of annexin VI and actin in secretory ameloblasts and odontoblasts of rat incisor

Summary Annexin VI and actin were detected by immunoblot analysis in the enamel- and dentin-related portions of dental tissues. Annexin VI was found mainly in the particulate fraction whereas actin was detected in both the soluble and particulate fractions. By immunoelectron microscopy, annexin VI antibodies conjugated with colloidal gold were seen to label the mitochondria, the cytosol and the nucleus of secretory ameloblasts and odontoblasts of rat incisor. In the processes of these cell, the plasmalemmal undercoat was labeled. Antiactin antibodies labeled the desmosome-like junctions, the cytosol, and the mitochondria of the cell bodies. Extensive labeling was seen at the periphery of the Tomes' processes and odontoblast processes. These results suggest that annexin VI may play a role in Ca²⁺-regulation in the cell bodies, especially as a calcium receptor protein in the mitochondria. Moreover, annexin VI and actin seem to be co-distributed in secretory processes. Thus, these proteins might be both involved in exocytotic and endocytotic events.     

Maturation-related changes in mass and elemental contents of secretory granules as measured by electron-microprobe

Summary The relationship between granule density, protein content, and Ca and S contents were studied in two secretory granule fractions, from parotid glands of the rat, previously shown to constitute different stages in granule maturation. The density of the lighter fraction was between 1.133 and 1.142 g/ml, while that of the heavier fraction was greater than 1.142 g/ml. The mean protein content of the denser granules was 12% greater than that of the lighter granules (P<0.03), while the dry-mass elemental concentrations in the two granule fractions were unchanged. These results indicate that protein is added to granules during the maturation process (presumably by vesicular traffic), and that the resulting increase in granule density is not driven simply by decrease in water content and/or increased concentrations of inorganic Ca or S in the granules. The elemental concentration values also indicate that the diffusible elements permeate the granule membrane during the fractionation procedures.     

American anthropologists looking through Taiwanese culture

Conclusion Anthropologists have too often supported — in their words, in their presences, and in their deeds — the paternalistic claims of rulers suppressing the very cultures they want to study. Much anthropological work legitimates substitution of the language of Beijing for Hakka and Holo, justifies ignoring Taiwanese culture, and subordinates consideration of its specific features to writing about Chinese civilization, just as Taiwanese are economically and politically subordinated to the ethnic minority dictatorship which still rules Taiwan under the fiction of being the government of China. The China that Arthur Wolf and others serve in return for support of their research from what purports to be the Republic of China is an egregious, but unfortunately not unique, example.Stephen O. Murray is with El Instituto Obregón, San Francisco, California. Keelung Hong is with the Cancer Research Institute, University of California, San Francisco.As is normal in anthropology, except for Taiwan, native terms are romanized in the native language (in the first author's recording of the second author's Daidiong idiolect, without indication of the extremely intricate tone differentia), not in the official language of the ethnic oligarchy ruling Taiwan (Beijinghua). Mainland place names are rendered in pinyin. We have followed the convention of treating Chinese and Taiwanese personal names as two words, because books are catalogued with such names. If personal names are considered as two words (an imposition of the hoary dogma that words in Sino-Tibetan languages are monosyllabic), it seems to us that both words should be capitalized. For Taiwanese placenames, we have not separated syllables by dashes or by spaces.     

Habitat selection and subsequent reproductive success in the beaugregory damselfish

Synopsis Male beaugregory damselfish,Stegastes leucostictus, were provided with three types of artificial breeding structures to determine if they change habitats based on past or future reproductive payoffs. All three site types quickly lured males away from their natural sites. In comparison to those living on natural sites, those using artificial sites were less likely to move to different areas and had a higher reproductive success. When given no choice, male reproductive success was correlated to structural type. A second experiment provided males with an additional structure after using the intermediate quality type for 2 months. Males would often initially use both sites but would eventually shift their spawning activity to the new site if it was of the same quality or better than the old one. However, males would not move if the new site was of inferior quality. When given a new site identical to the initial one, approximately half of the males shifted to the new site. There was no evidence that reproductive performance influenced a male's decision to use a new site.     

Characterization of the morphological, growth, and steroidogenic effect of TPA on mouse Y-1 adrenal cortical tumor cells in culture

The tumor-promoting agent 12-0-tetradecanoyl-phorbol-13-acetate (TPA) caused a time- and dose-dependent morphological change in Y-1 adrenocortical tumor cells. The morphological alteration was apparent 2 hr following addition of 1 microgram/ml TPA to cell cultures and became more striking with longer treatment times. Smaller doses of TPA took a longer time to produce an effect. Cultures grown in the presence of TPA exhibited more rounding and piling up of cells than similar cultures maintained in medium lacking TPA. These TPA-stimulated morphological changes were reversible, and after 24 hr in TPA-free media, the cultured cells began to flatten. After 96 hr in TPA-free media they resembled the control cultures. The reversibility of the morphological change was also dose dependent: cells treated with 1 microgram/ml TPA took a longer time to resume the typical control morphology than did cultures treated with 0.01 microgram/ml TPA. In addition, TPA treatment resulted in a decrease in cell growth rate, an increase in steroid production, and an increase in the localization of free catalytic units of cAMP-dependent protein kinase in the cytoplasm. The steroidogenic effect of ACTH on the cell population was inhibited in cultures maintained in TPA. The results of this study indicate that TPA induces morphological changes in the Y-1 adrenocortical tumor cell population while increasing steroidogenesis and the activation of cAMP-dependent protein kinase and decreasing cell growth rate.     

Structure of an S layer on a pathogenic strain of Aeromonas hydrophila.

Negative staining revealed a tetragonal surface array (S layer) on all the members of a serogroup of Aeromonas hydrophila which possess high virulence for fish. The S layers were similar on all the strains examined, with unit cell dimensions of approximately 12 nm. A single representative strain, strain TF7, was selected for further analysis. Freeze-cleaved and etched preparations and sections for electron microscopy showed that the S layer was the outermost component of the cell envelope. This was confirmed by observation of thin sections. Computer-generated enhancements of the negatively stained micrographs showed the subunit organization to a resolution of less than 4 nm. Two structural units of identical lattice constants alternated in the array in both axes, and one of them was apparently dominant as the center of mass. The lesser unit was rotated 20 degrees from the dominant axes of symmetry and was formed by the junction of linker projections from a corner of the four components of the dominant unit. This interpretation was supported by finding that the array consists of a single polypeptide (molecular weight, 52,000). The unit cell as defined showed p4 symmetry, and a = b = 12.2 nm.     

Plasmid profile analysis of a salmonellosis outbreak and identification of a restriction and modification system.

After an outbreak of salmonellosis in humans caused by Salmonella typhimurium bacteriophage type 135, 62 isolates from human, animal, and water sources were retained for further analysis. Most of the isolates (92%) could be placed in one of five plasmid pattern groups, with a majority containing a common 60-kilobase plasmid and a smaller 3.8-kilobase-pair plasmid. This small plasmid, pIMVS1, was labeled with [32P]phosphate and used as a probe in subsequent colony and Southern hybridization studies. We concluded that pIMVS1 from isolates obtained from humans was genetically different from plasmids of a similar size found in isolates from chickens. Studies to characterize pIMVS1 were undertaken to determine if it codes for known virulence factors. It did not appear to be associated with the formation of attachment pili or major outer membrane proteins. By using transposon mutagenesis techniques, Tn3(Apr) was inserted into pIMVS1, and the existence of a restriction and modification system was deduced.