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.     

Rapid resolution of phenylthiohydantoin amino acids by thin-layer chromatography on silica gel plates impregnated with transition metal ions

The resolution of a 15-component mixture of phenylthiohydantoin (PTH) amino acids using metal ion impregnated silica gel plates is reported. The spots are located by exposing the chromatograms to an iodine chamber. The method provides a rapid, simple, and less expensive chromatographic system, provides resolution for certain difficult combinations, and leaves the PTH amino acids unaltered chemically.     

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.     

Characterization of rat brain microsomal acyl-coenzyme A ligases: different enzymes for the synthesis of palmitoyl-coenzyme A and lignoceroyl-coenzyme A

Palmitic acid solubilized with Triton WR-1339 was converted to palmitoyl-CoA by microsomal membranes but lignoceric acid solubilized with Triton WR-1339 was not an effective substrate even though the detergent dispersed the same amount of these fatty acids and was also not inhibitory to the enzyme [I. Singh, R. P. Singh, A. Bhushan, and A. K. Singh (1985) Arch. Biochem. Biophys. 236, 418-426]. This observation suggested that palmitoyl-CoA and lignoceroyl-CoA may be synthesized by two different enzymes. We have solubilized the acyl-CoA ligase activities for palmitic and lignoceric acid of rat brain microsomal membranes with Triton X-100 and resolved them into three separate peaks (fractions) by hydroxylapatite chromatography. Fraction A (palmitoyl-CoA ligase) had high specific activity for palmitic acid and Fraction C (lignoceroyl-CoA ligase) for lignoceric acid. Specific activity of palmitoyl-CoA ligase for palmitic acid was six times higher than in Fraction C and specific activity of lignoceroyl-CoA ligase for lignoceric acid was four times higher than in Fraction A. At higher concentrations of Triton X-100 (0.5%), lignoceroyl-CoA ligase loses activity whereas palmitoyl-CoA ligase does not. Lignoceroyl-CoA ligase lost 60% of activity at 0.6% Triton X-100. Palmitoyl-CoA ligase (T1/2 of 4.5 min) is more stable at 40 degrees C than lignoceroyl-CoA ligase (T1/2 of 1.5 min). The pH optimum of palmitoyl-CoA ligase was 7.7 and that of lignoceroyl-CoA ligase was 8.4. Similar to our results with intact membranes, palmitic acid solubilized with Triton WR-1339 was converted to palmitoyl-CoA by palmitoyl-CoA ligase whereas lignoceric acid when solubilized with Triton WR-1339 was not able to act as substrate for lignoceroyl-CoA ligase. Since solubilized enzyme activities for synthesis of palmitoyl-CoA and lignoceroyl-CoA from microsomal membranes can be resolved into different fractions by column chromatography and demonstrate different properties, we suggest that in microsomal membranes palmitoyl-CoA and lignoceroyl-CoA are synthesized by two different enzymes.     

The transforming growth factor beta type II receptor can replace the activin type II receptor in inducing mesoderm.

The type II receptors for the polypeptide growth factors transforming growth factor beta (TGF-beta) and activin belong to a new family of predicted serine/threonine protein kinases. In Xenopus embryos, the biological effects of activin and TGF-beta 1 are strikingly different; activin induces a full range of mesodermal cell types in the animal cap assay, while TGF-beta 1 has no effects, presumably because of the lack of functional TGF-beta receptors. In order to assess the biological activities of exogenously added TGF-beta 1, RNA encoding the TGF-beta type II receptor was introduced into Xenopus embryos. In animal caps from these embryos, TGF-beta 1 and activin show similar potencies for induction of mesoderm-specific mRNAs, and both elicit the same types of mesodermal tissues. In addition, the response of animal caps to TGF-beta 1, as well as to activin, is blocked by a dominant inhibitory ras mutant, p21(Asn-17)Ha-ras. These results indicate that the activin and TGF-beta type II receptors can couple to similar signalling pathways and that the biological specificities of these growth factors lie in their different ligand-binding domains and in different competences of the responding cells.     

Correlation of phospholipid structure with functional effects on the nicotinic acetylcholine receptor. A modulatory role for phosphatidic acid.

Fourier transform infrared spectroscopy is used to characterize specific interactions between negatively charged lipids, such as phosphatidic acid, and the purified nicotinic acetylcholine receptor from Torpedo californica. The specific interaction of phosphatidic acid with acetylcholine receptor is demonstrated by the receptor-induced perturbation of the lipid ionization state, which is monitored using Fourier transform infrared bands arising from the phosphate head group. The acetylcholine receptor shifts the pKa of phosphatidic acid molecules adjacent to the receptor to a lower value by almost 2 pH units from 8.5 to 6.6. Decreased pH also leads to changes in ion channel function and to changes in the secondary structure of the acetylcholine receptor in membranes containing ionizable phospholipids. Phospholipase D restores functional activity of acetylcholine receptor reconstituted in an unfavorable environment containing phosphatidylcholine by generating phosphatidic acid. Lipids such as phosphatidic acid may serve as allosteric effectors for membrane protein function and the lipid-protein interface could be a site for activity-dependent changes that lead to modulation of synaptic efficacy.