Determination of the relative and absolute stereochemistry of a potent and α1A-selective adrenoceptor antagonist

The binding affinities and selectivities of antagonists Figure 1 and Scheme 2 for the α_1A-adrenoceptor are dependent on the stereochemical orientation of the groups at the C-4 and C-5 positions of the oxazolidinone ring. The unambiguous assignment of the relative and absolute configurations of the diastereomers of SNAP 7915 (Figure 1 and Scheme 2) is reported.     

Ethnomedicinal plant use by Lepcha tribe of Dzongu valley, bordering Khangchendzonga Biosphere Reserve, in North Sikkim, India

Lepcha is the oldest and the first tribe reported from Sikkim, India; majority of its population inhabiting in Dzongu valley, an officially demarcated reserve for Lepcha community, bordering Khangchendzonga Biosphere Reserve, in north district. Lepchas of Dzongu are known for their retention of rich cultural heritage. In view of the on-going cultural and economic changes brought in by the process of globalization, the immediate need was felt to document in details the under-explored ethnomedicinal practices of Lepchas of Dzongu valley. This paper reports 118 species, belonging to 71 families and 108 genera, under ethnomedicinal utility by the Lepchas for curing approximately 66 ailments, which could be grouped under 14 broad categories. Zingiberaceae appeared as the most used family (8 species and 5 genera). As per use pattern, maximum of 30.50% species are to cure stomach related disorders/ailments, followed by 19.49% for curing cut, wounds, inflammation, sprains and joint pains. Administration of medicine orally is recorded in 75% cases. Root and rhizome harvesting targeted 30 species. The changing scenario over time both at socio-cultural front and passing traditional knowledge interests from older to younger generation and rich ethnomicinal wealth of the oldest tribe of Sikkim are discussed in the light of conservation strategies and techniques to adopt.     

Induction of interleukin-2 receptor by tumor necrosis factor α on cultured ovarian tumor-associated lymphocytes

Summary We have recently reported that autologous tumor-specific cytotoxic T lymphocyte (CTL) lines and clones can be developed from lymphocytes infiltrating ovarian malignant ascites (TAL). In this study, we investigated the biological effects of tumor necrosis factor (TNF) in the induction, expansion, long-term proliferation and lytic function of CD8⁺ TAL. TNF up-regulated the IL-2 receptor (IL-2R) chain (Tac antigen) on the surface of CD3⁺ CD8⁺ CD4^– TAL, enhanced the proliferation of autologous tumor-specific CTL, and potentiated their lytic function in long-term cultures. Furthermore, in the induction and expansion phase of CD8⁺ TAL, the presence of TNF was associated with a selective increase in CD8⁺ IL-2R⁺ (Tac⁺) cells, and subsequent decrease in CD4⁺ IL-2R⁺ (Tac⁺) cells. These results suggest that the observed facilitation of the outgrowth of CD8⁺ cells in TAL cultures may be due, at least in part, to the up-regulation of IL-2R, and indicate the usefulness of TNF in the analysis of signalling in autologous tumor-reactive CTL.     

Inhibition of red light-induced seed germination by indole-3-acetic acid inHygrophila auriculata

Seed germination inHygrophila auriculata (Schumach.) Haines was found to be under phytochrome control. Exogenous indole-3-acetic acid (IAA) application at concentrations greater than 1×10^–6 M inhibited germination in the dark, as well as in the light. Red light-induced radicle growth, prior to radicle protrusion through seed coverings and measured as an angle formed by the radicle with the seed axis, was found to be inhibited by IAA. Delay in application of IAA to red light-irradiated seeds resulted in a gradual increase in percent germination, which probably corresponded to the time-course of Pfr action. It is suggested that exogenously applied IAA probably reimposes dormancy in red light-induced seeds ofHygrophila auriculata.     

Production of acetate by mutant strains of Clostridium thermoaceticum

Summary Mutant strains were derived from Clostridium thermoaceticum ATCC 39 289 by treatment with chemical mutagenic agents and selective enrichment procedures. Some mutant strains exhibited growth when cultured in media containing 20 mabetm (1.75 g l^–1) pyruvate of high-magnesium lime (dolime) above pH 6.0. One strain (G-20) grew and produced acetate when 80 mabetm (7 gl^–1) pyruvate or 50 mabetm (2.3 g l^–1) formate at pH 5.6 was the sole energy source. In a fed-batch process controlled at pH 6.2, this mutant produced 52.5 g l^–1 acetate (equivalent to 72.5 g l^–1 Na acetate) and 67 g l^–1 calcium-magnesium acetate (CMA) in 140 h when dolime was the neutralizing agent, with 93% substrate utilization. This mutant strain holds promise for CMA production due to its better tolerance of dolime and its ability to synthesize high levels of acetic acid. Offprint requests to: S. R. Parekh     

Production of glycerol by hansenula anomala

Production of glycerol by Hansenula anomala in molasses-corn steep liquor based media was studied. The accumulation and yield of glycerol was dependent on the medium composition and aeration rate; pH control did not affect the yield. Intermittent addition of sugar during fermentation resulted in significant increase in production of glycerol.     

SO2-catalysed prehydrolysis of coniferous wood for ethanol production

Summary This paper reports studies of large scale, 1500 kg/h, SO₂-catalysed prehydrolysis of coniferous wood chips, samples then being hydrolyzed by a wood-saccharifying enzyme system followed by fermentation to ethanol in the laboratory. Hemicellulose hydrolysis using SO₂ catalyst (prehydrolysis) was found to be more effective than steam alone (autohydrolysis). Prehydrolysis time was 2 min, with steam pressure at 1.2 to 1.7 MPa (175 to 250 psig), and SO₂ catalyst 2.0 to 2.6% on dry wood. The amount of sugars recovered upon enzyme saccharification of the prehydrolysed wood was about 70% of the weight of the wood. When these combined hemicellulose and cellulose sugars were fermented by a pentose-fermenting strain of yeast,Pichia stipitis R, 372 L ethanol/tonne of (dry) wood was obtained.     

Post-translational modification of proteins and the discovery of new medicine

Post-translational modifications are fundamental to processes controlling behaviour, including cellular signaling, growth and transformation. As the molecular basis of protein modifications in normal and disease processes are becoming better defined, so new strategies for designing therapeutic entities to control complex disease processes are emerging.     

Effect of cell cycle on the regulation of the cell surface and secreted forms of type I and type II human tumor necrosis factor receptors

The cell cycle has been shown to regulate the biological effects of human tumor necrosis factor (TNF), but to what extent that regulation is due to the modulation of TNF receptors is not clear. In the present report we investigated the effect of the cell cycle on the expression of surface and soluble TNF receptors in human histiocytic lymphoma U-937. Exposure to hydroxyurea, thymidine, etoposide, bisbensimide, and democolcine lead to accumulation of cells primarily in G₁/S, S, S/G₂/M, G₂/M, and M stages of the cell cycle, respectively. Whilie no significant change in TNF receptors occurred in cells arrested in G₁/S or S/G₂ stages, about a 50% decrease was observed in cells at M phase of the cycle. Scatchard analysis showed a reduction in receptor number rather than affinity. In contrast, cells arrested at S phase (thymidine) showed an 80% increase in receptor number. The decrease in the TNF receptors was not due to changes in cell size or protein synthesis. The increase in receptors, however, correlated with an increase in total protein synthesis (to 3.8-fold of the control levels). A proportional change was observed in the p60 and p80 forms of the TNF receptors. A decrease in the surface receptors in cells arrested in M phase correlated with an increase in the amount of soluble receptors. The cellular response to TNF increased to 8- and 2-fold in cells arrested in G₁ and S phase, respectively; but cells at G2/M phase showed about 6-fold decrease in response. In conclusion, our results demonstrate that the cell cycle plays an important role in regulation of cell-surface and soluble TNF receptors and also in the modulation of cellular response. © 1995 Wiley-Liss, Inc.