“Unblocking” Serum Activity <Emphasis Type="Italic">in vitro</Emphasis> in the Polyoma System may Correlate with Antitumour Effects of Antiserum <Emphasis Type="Italic">in vivo</Emphasis>

In a variety of tumour systems, individuals carrying progressively growing neoplasms have lymphoid cells with a specific cytotoxic effect on cultured tumour cells from the same individual^1–4. Since the sera of tumour-bearing individuals have been shown to prevent tumour cell destruction by immune lymphocytes in vitro^2,5–8 and since this serum blocking activity appears early in primary and transplant tumour development^5,7, it has been suggested that the appearance of this serum blocking activity might be responsible for the progressive growth of tumours in individuals having cytotoxic lymphocytes. Counteraction of this blocking activity would thus be of primary importance in facilitating the function of an already existing or bolstered cell-mediated immunity. The serum blocking activity might be inhibited in various ways, by preventing the formation of blocking antibody or by interfering with its action (“unblocking”), as demonstrated in Moloney sarcoma regressor sera⁹. This type of serum also has a therapeutic effect on Moloney sarcomas in vivo^10,11, which has been tentatively attributed to its unblocking activity^8,9 or, possibly, to a complement-dependent cytotoxicity¹⁰. Tumour growth in the Moloney sarcoma system, however, might be due in part to continuous recruitment of neoplastic cells by virus-induced transformation and so the therapeutic effect could be due to a virus-neutralizing serum activity^9,10.     

On the mechanism of ATP-induced shape changes in the human erythrocyte membranes: the role of ATP

In the preceding paper (Sheetz, M. and S.J. Singer. 1977. J Cell Biol. 73:638-646) it was shown that erythrocyte ghosts undergo pronounced shape changes in the presence of mg-ATP. The biochemical effects of the action of ATP are herein examined. The biochemical effects of the action of ATP are herein examined. Phosphorylation by ATP of spectrin component 2 of the erythrocyte membrane is known to occur. We have shown that it is only membrane protein that is significantly phosphorylated under the conditions where the shape changes are produced. The extent of this phosphorylation rises with increasing ATP concentration, reaching nearly 1 mol phosphoryle group per mole of component 2 at 8mM ATP. Most of this phosphorylation appears to occur at a single site on the protein molecule, according to cyanogen bromide peptide cleavage experiments. The degree of phosphorylation of component 2 is apparently also regulated by a membrane-bound protein phosphatase. This activity can be demonstrated in erythrocyte ghosts prepared from intact cells prelabeled with [(32)P]phosphate. In addition to the phosphorylation of component 2, some phosphorylation of lipids, mainly of phosphatidylinositol, is also known to occur. The ghost shape changes are, however, shown to be correlated with the degree of phosphorylation of component 2. In such experiment, the incorporation of exogenous phosphatases into ghosts reversed the shape changes produced by ATP, or by the membrane-intercalating drug chlorpromazine. The results obtained in this and the preceding paper are consistent with the proposal that the erythrocyte membrane possesses kinase and phosphates activities which produce phosphorylation and dephosphorylation of a specific site on spectrin component 2 molecules; the steady-state level of this phosphorylation regulates the structural state of the spectrin complex on the cytoplasmic surface of the membrane, which in turn exerts an important control on the shape of the cell.     

Selective inhibition of prostaglandin biosynthesis by gold salts and phenylbutazone

Gold salts and phenylbutazone selectively inhibit the synthesis of PGF_2α and PGE₂ respectively. Lowered production of one prostaglandin species is accompanied by an increased production of the other. Selective inhibition by these drugs was observed in the presence of adrenaline, reduced glutathione and copper sulphate under conditions when most anti-inflammatory compounds inhibited PGE₂ and PGF_2α syntheses equally. It is postulated that selective inhibitors may have a different mode of action and beneficial effects may be related to the endogenous ratio of PGE to PGF required for normal function.     

The discovery of the benzazepine class of histamine H3 receptor antagonists

This Letter describes the discovery of a novel series of H₃ receptor antagonists. The initial medicinal chemistry strategy focused on deconstructing and simplifying an early screening hit which rapidly led to the discovery of a novel series of H₃ receptor antagonists based on the benzazepine core. Employing an H₃ driven pharmacodynamic model, the series was then further optimised through to a lead compound that showed robust in vivo functional activity and possessed overall excellent developability properties.     

A web server to locate periodicities in a sequence

Summary : FT is a tool written in C++, which implements the Fourier analysis method to locate periodicities in aminoacid or DNA sequences. It is provided for free public use on a WWW server with a Java interface. Availability : The server address is http://o2.db. uoa.gr/FT Contact : shamodr@atlas.uoa.gr      

Headwater streams and forest management: Does ecoregional context influence logging effects on benthic communities?

Effects of forest management on stream communities have been widely documented, but the role that climate plays in the disturbance outcomes is not understood. In order to determine whether the effect of disturbance from forest management on headwater stream communities varies by climate, we evaluated benthic macroinvertebrate communities in 24 headwater streams that differed in forest management (logged-roaded vs. unlogged-unroaded, hereafter logged and unlogged) within two ecological sub-regions (wet versus dry) within the eastern Cascade Range, Washington, USA. In both ecoregions, total macroinvertebrate density was highest at logged sites (P = 0.001) with gathering-collectors and shredders dominating. Total taxonomic richness and diversity did not differ between ecoregions or forest management types. Shredder densities were positively correlated with total deciduous and Sitka alder (Alnus sinuata) riparian cover. Further, differences in shredder density between logged and unlogged sites were greater in the wet ecoregion (logging × ecoregion interaction; P = 0.006) suggesting that differences in post-logging forest succession between ecoregions were responsible for differences in shredder abundance. Headwater stream benthic community structure was influenced by logging and regional differences in climate. Future development of ecoregional classification models at the subbasin scale, and use of functional metrics in addition to structural metrics, may allow for more accurate assessments of anthropogenic disturbances in mountainous regions where mosaics of localized differences in climate are common.     

Intra-specific competition and the radial development of wood density, microfibril angle and modulus of elasticity in plantation-grown Eucalyptus nitens

In eucalypt plantations managed for solid-wood products, radial trends in wood density, microfibril angle (MFA) and stiffness (modulus of elasticity, MoE) are properties of potential commercial importance that can be affected by competition from neighbouring trees. In this study, wood properties at breast height (1.3?m) were studied on radial strips prepared from 12-mm pith-to-bark wood cores taken from 20 trees in a 22-year-old Eucalyptus nitens (Deane and Maiden) Maiden thinning trial in north-eastern Tasmania, Australia. Thinning treatments were applied at age 6?years. Trees were sampled from each of the 200, 400?stems ha^?1 and unthinned control treatments. Intra-specific competition for each sampled tree was estimated using the basal area growth of surrounding trees. SilviScan? technology was used to produce radial profiles of wood density, MFA and MoE. Results indicate a reduction in intra-specific competition through thinning of E. nitens plantations at an early age leads to a transient increase in MFA but has no significant effect on wood density or the intra-annual cycle of wood density. The correlation between the level of intra-specific competition and initial change in MFA following thinning, and a significant relationship between tree shape and mean MFA at breast height suggests the change in MFA is a post-thinning response to increased exposure and wind sway.     

Sapwood hydraulic conductivity and leaf area – sapwood area relationships following thinning of a Eucalyptus nitens plantation

This study tested the hypothesis that the relationship between leaf area (projected, or one‐sided) and sapwood area in Eucalyptus nitens (Deane and Maiden) Maiden is affected by thinning treatment. However, no difference in the relationship between leaf area and sapwood area was found 8 years after thinning. This result suggests that a single regression equation can be used to predict the leaf area of trees in thinned and unthinned stands. The relationship was non‐linear, implying a causal relationship between growth rate and the ratio of leaf area to sapwood area (A_l : A_s). Sapwood hydraulic conductivity increased by approximately 100% from breast height to crown base, whereas sapwood area decreased by 19%. This implies that the efficiency of water transport through the sapwood increased by 60% along this length. This conclusion is supported by the A_l : A_s relationships which showed that the sapwood area at crown base supported, on average, close to 60% more leaf area than a similar amount of sapwood area at breast height. That large trees in this study had greater hydraulic conductivity and higher A_l : A_s lends support to the argument that resource capture, and hence growth rate, influence sapwood hydraulic conductivity.     

Amiloride does not alter NaCl avoidance in Fischer-344 rats

Fischer-344 (F-344) rats differ from other common rat strains in that they fail to show any preference for NaCl at any concentration in two- bottle preference tests. Because 100 microM amiloride partially blocks the NaCl-evoked chorda tympani (CT) response in electrophysiological studies, we tested NaCl preference (0.068-0.273 M) in F-344 rats with and without 100 microM amiloride solution as the solvent. A third group was tested with unadulterated NaCl solutions following CT transection. Amiloride had no significant effect on the NaCl preference-aversion function, whereas CT transection significantly reduced NaCl avoidance. These results suggest that the amiloride-sensitive component of the NaCl response is not necessary for F-344 rats to display avoidance of NaCl, but the entire CT input is.