Gigantecin: A novel antimitotic and cytotoxic acetogenin,with nonadjacent tetrahydrofuran rings,fromGoniothalamus giganteus (Annonaceae)

Summary Gigantecin (I), a novel tetrahydroxy-di-tetrahydrofuran fatty acid -lactone (acetogenin), was isolated from an ethanolic extract of the stem bark ofGoniothalamus giganteus Hook. f., Thomas (Annonaceae), by means of activity-directed fractionation (brine shrimp lethality test). This new compound is extremely cytotoxic to human tumor cells, inhibits crown gall tumors on potato discs, and is active in an assay designed to detect antimitotic agents (9 ASK).     

Saccadic oscillations facilitate ocular perfusion from the avian pecten

THE evolution of the eye is constrained by two conflicting requirements--good vascular perfusion of the retina, and an optical path through the retina that is unobstructed by blood vessels. Birds are interesting in that they have higher metabolic rates and thicker retinas than mammals, but have no retinal blood vessels. Nutrients and oxygen must thus reach the neurons of the inner retina either from the choroid through 300 micron of metabolically very active retina, or from the pecten, a pleated vascular structure protruding from the head of the optic nerve into the vitreous chamber, and more than a centimetre away from some retinal neurons. Despite the diffusional distance involved, several lines of evidence indicate that the pecten is the primary source of nutrients for the inner retina: the presence of an oxygen gradient from pecten to retina, the large surface area produced by macroscopic folds and by microscopic infoldings of the luminal and external surfaces of the capillary endothelium, extrusion of circulating fluorescein, high content of carbonic anhydrase and alkaline phosphatase, and retinal impairments after pecten ablation. Another peculiarity of birds, their saccadic oscillations, occur with a large cyclotor-sional component during every saccadic eye movement. In different species, saccades, which occur at intervals of 0.5-40 s, have up to 13 oscillations with frequencies of 15-30 Hz and ampliá-tudes of about 10 degrees. Therefore, as much as 12% of some birds' total viewing time may be subject to the image instability caused by the oscillations. Using fluorescein angiography, we show here that during every saccade, the pecten acts as an agitator which propels perfusate towards the central retina much more effectively than is observed during intersaccadic intervals.     

Evidence from carbon isotope measurements for diverse origins of sedimentary hydrocarbons

The organic matter found in sedimentary rocks must derive from many sources; not only from ancient primary producers but also from consumers and secondary producers. In all of these organisms, isotope effects can affect the abundance and distribution of 13C in metabolites. Here, by using an improved form of a previously described technique in which the effluent of a gas chromatograph is continuously analysed isotopically, we report evidence of the diverse origins of sedimentary organic matter. The record of 13C abundances in sedimentary carbonate and total organic carbon can be interpreted in terms of variations in the global carbon cycle. Our results demonstrate, however, that isotope variations within sedimentary organic mixtures substantially exceed those observed between samples of total organic carbon. Resolution of isotope variations at the molecular level offers a new and convenient means of refining views both of localized palaeoenvironments and of control mechanisms within the global carbon cycle.     

Bovine microvascular endothelial cells of separate morphology differ in growth and response to the action of interferon-γ

Five cell types recently isolated from the bovine corpus luteum differed in their epithelioid morphology and their cytoskeleton, but shared common criteria of microvascular endothelial cells^1,2. To give strong evidence for the separate entity, the growth rate of the 5 phenotypically different cells was studied. They were seeded at low density on day 0. Most of these cells were treated with 200 to 1000 U recombinant bovine interferon- (IFN-) for 3 days. The untreated remainder served as controls. Cell counts were made for all cultures on days 4, 7, 10 and 13. morphology: 13 d after treatment with IFN- senescent cells as well as intact cells occurred in cultures of cell types 1 to 4. Cultures of cell type 5 were apparently unchanged and resembled their untreated counterparts. Desminpositive cells in cultures of cell type 2 developed cell processes. Growth rate: In the absence of IFN-, the growth rate was high for cell types 3 and 4, moderate for cell type 1, and low for cell types 2 and 5. The presence of IFN- caused anti-proliferative effects. These were higher for cell types 3 and 4 than for cell types 1 and 2. IFN- could be cytotoxic on cell type 3. In contrast, the cytokine tended to support the cell growth of cell type 5. These findings substantiate the postulate that endothelial cells exhibiting separate morphology in culture also function differently.     

Presence of hsp65 in bacterial extracts (OM-89): A possible mediator of orally-induced tolerance?

Heat shock proteins (HSP) have been implicated in rodent models of autoimmunity, particularly arthritis, and there is suggestive though inconclusive evidence that they may also play a role in human autoimmune disease. The simplest hypothesis is based on molecular mimicry due to the amino-acid sequence homology between mammalian and microbial HSP. Recently OM-89, an extract of several strains ofEscherichia coli, has shown some efficacy in the treatment of rheumatoid arthritis (RA) when taken orally. Using species-specific antibodies, we show here that OM-89 contains the 65 kDa HSP (hsp65), while hsp65 was not detected in another bacterial extract containing other microorganisms, includingStaphylococcus aureus (OM-85). We suggest that if the human homologue of hsp65 is a relevant target antigen in the human disease, the efficacy of the preparation could be due to induction of oral tolerance or to switching the Th1 response towards Th2. Alternatively, even if the human hsp65 is not a target molecule in RA joints, OM-89 may evoke bystander suppression of joint inflammation via induction of TGF-secreting effector cells. These hypotheses should be tested in further studies.     

Occurrence of 3-epi-22-deoxy-20-hydroxyecdysone and its phosphoric ester in diapause eggs of the silkworm,Bombyx mori

Ecdysteroids in diapause eggs of the silkworm,Bombyx mori, were analyzed using high-performance liquid chromatography (HPLC) combined with radioimmunoassay (RIA). A relatively large amount of an unidentified free ecdysteroid and its phosphoric ester (conjugated form) were detected. These two compounds were isolated by a combination of column chromatography on silicic acid, thin-layer chromatography (TLC), and HPLC using a reverse-phase (RP) column. The purified compounds were identified as 3-epi-22-deoxy-20-hydroxyecdysone (22d20E) and 3-epi-22-deoxy-20-hydroxyecdysone 2-phosphate (22d20E2P) by means of mass spectrometry and nuclear magnetic resonance spectroscopy. to our knowledge, this is the first report of 22d20E and 22d20E2P.     

Sex pheromone of the pine sawflyDiprion pini (Hymenoptera: Diprionidae): Chemical identification,synthesis and biological activity

The main component of the sex pheromone secretion of femaleDiprion pini L. (Hymenoptera: Diprionidae) from insects collected both in Finland and in France has been identified as athreo-3,7-dimethyl-2-tridecanol (8 ng per female) stereoisomer by GC-MS and synthesis. The secretion also contains lower and higher homologues in small amounts (1–4% of the main component). Combined gas chromatographic-electroantennographic detection showed activity in both natural and esterified extracts (acetates and propionates); the esters of the main component gave the largest responses. The acetates and propionates of the eight stereoisomers of 3,7-dimethyl-2-tridecanol were synthesized from enantiomerically highly enriched (>99% ee) building blocks. The stereochemistry of the main component was established to be (2S,3R,7R)-3,7-dimethyl-2-tridecanol by GC analysis of the natural material. It was purified by liquid chromatography prior to the GC analysis of both its pentafluorobenzoates and its isopropylcarbamates on a non-chiral polar column (ECD) and a chiral column (NPD), respectively. Field tests demonstrated that both the acetate and propionate of the main component (100 g of each applied on cotton roll dispensers) were active in attracting males, with or without the presence of several of the minor compounds. Experiments with smaller amounts of the acetate and the propionate (1 g in France and 50 g in Finland) demonstrated that the propionate was more active than the acetate, and that it also caught more males than a blend of the two compounds.     

The first known use of vermillion

Vermillion has been shown to be useful in preserving human bones from 5000 years ago. Remarkably well-preserved human bones have been found in the dolmenic burial La Velilla in Osorno (Palencia, Spain), carefully covered by pulverized cinnabar (vermillion) which ensured their preservation even in non-favorable climatic conditions. We believe the red powder was deliberately deposited for preservative use because no cinnabar mine is to be found within 160 km, because of the large amount (hundreds of kilograms) used, and because its composition, red mercuric sulphide, is similar to that of preparations used in technical embalming. This finding pushes back the data of the use of mercury ore for preservation by four millennia in South America, and by at least one millennium in the Old World. Chemical and thermal analyses of vermillion in La Velilla have demonstrated its great purity and shown that the cinnabar was pulverized and washed (but not heated), producing a bright red-orange tone.