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).     

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.     

2-Methoxybenzoyl phosphate: a new substrate for continuous fluorimetric and spectrophotometric acyl phosphatase assays

A new aromatic acyl phosphate, 2-methoxybenzoyl phosphate, has been synthesized. The compound shows an intrinsic fluorescence; it displays an intense emission band at 390 nm upon excitation in the near UV region. This band practically disappears after hydrolysis of the product. On the other hand, the product displays differences in the near UV absorption spectra measured before and after hydrolysis. The at 301 nm is 2720 M^–1 cm^–1, a value that is 4.3-fold higher than that of benzoyl phosphate (the usual substrate for acylphosphatase assay) at 283 nm. The main kinetic parameters of three different acylphosphatase molecular forms (the muscular isoenzyme and two subtypes of the organ common isoenzyme) were determined using both benzoyl phosphate and 2-methoxybenzoyl phosphate as substrates, and then compared. These kinetic data and the UV absorption and fluorescence properties of 2-methoxybenzoyl phosphate sugest that this compound has better substrate features than benzoyl phosphate, and can be used for both high sensitivity continuous fluorimetric and UV absorption spectrophotometric assays of acylphosphatase.     

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.     

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.