Anticancer indole alkaloids of Ervatamia heyneana

The wood and stem bark of Ervatamia heyneana (Apocynaceae) yielded 14 indole alkaloids and 3 triterpenoids. Six of these isolates, camptothecin (2), 9-methoxycamptothecin (3), coronaridine (1), pericalline (25), heyneatine (18) and 10-methoxyeglandine- N-oxide (4) displayed cytotoxic activity. Three of the indole alkaloids 18, 4 and 10-hydroxycoronaridine (8) are new members in the iboga series and their structures were determined by a combination of spectral interpretation and chemical correlation.     

Two classes of spontaneous miniature excitatory junction potentials and one synaptic vesicle class are present in the ray electrocyte

Summary Cross sections (1–2 mm thick) of the ray (Raja) tail were secured to a dish and immersed in elasmobranch saline. Spontaneous miniature excitatory junction potentials (MEJPs) were recorded by advancing a 50 k, KCl filled electrode into the electric organ (20 V peak-to-peak baseline noise). Data were filmed, and/or recorded on magnetic tape for computer analyses. Intracellularly recorded MEJP amplitude histograms showed a peak at 60 V and had a right-hand skew with MEJPs up to 0.5 mV. The small peak amplitude and the skewed amplitude distribution of intracellularly recorded MEJPs result from the relatively low input resistance and the short space constant of the electrocyte coupled with the dispersed synapses on the electrocyte. At 23 °C the intracellularly recorded MEJP frequency ranged from 1–10 MEJPs/s. The MEJPs became larger and became focally recorded as the electrode was advanced against the intracellular surface of the innervated membrane of the electrocyte. Focal extracellular MEJPs (reversed polarity) were also recorded with the electrode positioned against the outside surface of the innervated side of the electrocyte. The frequency of focally recorded intracellular MEJPs was increased (up to 40/s) when the electrode was pushed against the membrane. Focal MEJP frequencies decreased to a few/min within 5–10 min but the mean amplitude of 3–5 mV remained constant. Decreases in amplitude and frequency in focally recorded intracellular MEJPs are attributed to changes in electrode pressure against the membrane. Amplitude histograms were constructed from focally recorded intracellular or extracellular MEJPs which showed the same time characteristics. The focal MEJP amplitude histograms have two distinct classes, each forming a bell-shaped distribution. It is concluded that both classes are generated at the electrode tip. The smaller class of MEJPs has a mean 1/10th that of the larger class and composes about 2% of the MEJPs. The small class is analogous to the sub-MEPP class found in the frog sartorius (Kriebel and Gross 1974) and mouse diaphragm (Kriebel et al. 1976, 1982). Distributions of synaptic vesicle diameters are slightly log normal (right hand skew) such that the mean diameter (57 nm) is slightly larger than the modal value (52 nm). Vesicles touching the membrane were of the same size and diameter distribution as the entire vesicle population. The profiles of the distributions are smooth and suggest only 1 class of synaptic vesicle based on diameter.     

Anticancer sesquiterpene lactones of Michelia compressa (magnoliaceae)

Investigation of the cytotoxic active components of Michelia compressa afforded two new cytotoxic sesquiterpene lactones, michelenolide and micheliolide. Parthenolide, costunolide, santamarine, reynosin and liriodenine were also isolated and exhibited cytotoxic activity. The known sesquiterpene lactones, lanuginolide and dihydroparthenolide, were isolated but were not active. Two other new inactive sesquiterpene lactones, compressanolide and dihydroreynosin, were also obtained. The structures of michelenolide and micheliolide were confirmed by partial synthesis from parthenolide and the structure of compressanolide by partial synthesis from dihydroparthenolide.     

Inhibition of amino acyl tRNA synthetase activity by copper complexes of two metal binding ligands. N-Methyl isatin beta-thiosemicarbazone and 8-hydroxyquinoline.

Copper complexes of N-methyl isatin beta-thiosemicarbazone, 1-formyl isoquinoline thiosemicarbazone and thiosemicarbazide inhibit amino acyl tRNA synthetase activity. Copper complexes of 8-hydroxyquinoline and 8-mercaptoquinoline also inhibit. The 1 : 1 ligand-metal complex is significantly more active than the 2 : 1 complex. The free ligand alone and copper sulfate alone have little, if any, effect. These complexes have no effect on the ATP-PPi exchange reaction and do not cause deacylation of amino acyl tRNAs. This indicates that the process inhibited by these complexes is the amino acylation reaction. This is the first report that these copper binding ligands can inhibit enzymatic processes which involve nucleic acids but which are not viral, bacterial or mammalian cell polymerases.     

Functional changes in human leukemic cell line HL-60. A model for myeloid differentiation

Polar solvents induce terminal differentiation in the human promyelocytic leukemia cell line HL-60. The present studies describe the functional changes that accompany the morphologic progression from promyelocytes to bands and poly-morphonuclear leukocytes (PMN) over 9 d of culture in 1.3 percent dimethylsulfoxide (DMSO). As the HL-60 cells mature, the rate of O(2-) production increase 18-fold, with a progressive shortening of the lag time required for activation. Hexosemonophosphate shunt activity rises concomitantly. Ingestin of paraffin oil droplets opsonized with complement or Ig increases 10-fold over 9 d in DMSO. Latex ingestion per cell by each morphologic type does not change significantly, but total latex ingestion by groups of cells increases with the rise in the proportion of mature cells with greater ingestion capacities. Degranulation, as measured by release of β-glucuronidase, lysozyme, and peroxidase, reaches maximum after 3-6 d in DMSO, then declines. HL-60 cells contain no detectable lactoferrin, suggesting that their secondary granules are absent or defective. However, they kill staphylococci by day 6 in DMSO. Morphologically immature cells (days 1-3 in DMSO) are capable of O(2-) generation, hexosemonophosphate shunt activity, ingestion, degranulation, and bacterial killing. Maximal performance of each function by cells incubated in DMSO for longer periods of time is 50-100 percent that of normal PMN. DMSO- induced differentiation of HL-60 cells is a promising model for myeloid development.     

Indole alkaloids from the leaves of Philippine Alstonia scholaris

The first seco-uleine alkaloids, manilamine (1) (18-hydroxy-19,20-dehydro-7,21-seco-uleine) and N4-methyl angustilobine B (2), were isolated from the (pH 5) alkaloid extract of Philippine Alstonia scholaris leaves together with the known indole alkaloids 19,20-(E)-vallesamine (3), angustilobine B N4-oxide (4), 20(S)-tubotaiwine (5), and 6,7-seco-angustilobine B (6). The structure of the alkaloids was established from MS and NMR experiments.     

Multifactorial inheritance in type 1 diabetes

To date, twelve separate chromosome regions have been implicated in the development of human type 1 (insulin-dependent) diabetes mellitus. The major disease locus, IDDM1 in the major histocompatibility complex (MHC) on chromosome 6p21, accounts for about 35% of the observed familial clustering and its contribution to disease susceptibility is likely to involve polymorphic residues of class II molecules in T-cell-mediated autoimmunity. IDDM2 is encoded by a minisatellite locus embedded in the 5 regulatory region of the insulin gene. Familial clustering of disease can be explained by the sharing of alleles of at least 10 loci. IDDM1 and IDDM2 interact epistatically. For a multifactorial disease, such as type 1 diabetes, important information concerning the pathways and mechanisms involved can be gained from examining such interactions between loci, using methods that simultaneously take account of the joint effects of the various underlying genetic components.     

Quandaries of a decade‐long restoration experiment trying to reduce invasive species: beat them,join them,give up,or start over?

We evaluate the outcomes and consequences of a decade‐long restoration project in a Hawaiian lowland wet forest as they relate to long‐term management actions. Our initial study was designed both to promote native biodiversity and to develop knowledge that would enable land management agencies to restore invaded forests. Our premise of success followed the prevalent perception that short‐term management, such as removal of invasive species, ideally translates into long‐term and sustainable restoration. We were therefore disappointed and perhaps discouraged in our results—little recovery of native biodiversity despite ongoing and labor‐intensive management. Not only did we fail to return the invaded forest to a native‐dominated system but also our efforts lead to recruitment of new non‐native species assemblages. The sobering truth of many restoration projects in Hawaii and elsewhere is that we can never completely walk away and “consider the job finished,” or we have to accept that some ecosystems cannot be returned to an all‐native state. Essentially, costs of restoration may outweigh the accomplishment. This setback gave us an opportunity to reconsider and modify our initial approach. By starting over with a new direction using both native and non‐invasive but non‐native species, we have adopted a new philosophy of “join them.” In our revision, we changed the players in the game by following invasive species removal with outplantings of native and non‐invasive non‐native species that will functionally fill missing roles in the ecosystem. We link social interest in the new experiment to changing attitudes about naturalness.     

Physiological and morphological variation in Metrosideros polymorpha, a dominant Hawaiian tree species, along an altitudinal gradient: the role of phenotypic plasticity

Metrosideros polymorpha, a dominant tree species in Hawaiian ecosystems, occupies a wide range of habitats. Complementary field and common-garden studies of M. polymorpha populations were conducted across an altitudinal gradient at two different substrate ages to ascertain if the large phenotypic variation of this species is determined by genetic differences or by phenotypic modifications resulting from environmental conditions. Several characteristics, including ecophysiological behavior and anatomical features, were largely induced by the environment. However, other characteristics, particularly leaf morphology, appeared to be mainly determined by genetic background. Common garden plants exhibited higher average rates of net assimilation (5.8 μmol CO₂ m⁻² s⁻¹) and higher average stomatal conductance (0.18 mol H₂O m⁻² s⁻¹) than their field counterparts (3.0 μmol CO₂ m⁻² s⁻¹, and 0.13 mol H₂O m⁻² s⁻¹ respectively). Foliar δ¹³C of most common-garden plants was similar among sites of origin with an average value of −26.9‰. In contrast, mean values of foliar δ¹³C in field plants increased substantially from −29.5‰ at low elevation to −24.8‰ at high elevation. Leaf mass per unit area increased significantly as a function of elevation in both field and common garden plants; however, the range of values was much narrower in common garden plants (211–308 g m⁻² for common garden versus 107–407 g m⁻² for field plants). Nitrogen content measured on a leaf area basis in common garden plants ranged from 1.4 g m⁻² to 2.4 g m⁻² and from 0.8 g m⁻² to 2.5 g m⁻² in field plants. Photosynthetic nitrogen use efficiency (PNUE) decreased 50% with increasing elevation in field plants and only 20% in plants from young substrates in the common garden. This was a result of higher rates of net CO₂ assimilation in the common garden plants. Leaf tissue and cell layer thickness, and degree of leaf pubescence increased significantly with elevation in field plants, whereas in common garden plants, variation with elevation of origin was much narrower, or was entirely absent. Morphological characteristics such as leaf size, petiole length, and internode length decreased with increasing elevation in the field and were retained when grown in the common garden, suggesting a potential genetic basis for these traits. The combination of environmentally induced variability in physiological and anatomical characteristics and genetically determined variation in morphological traits allows Hawaiian M. polymorpha to attain and dominate an extremely wide ecological distribution not observed in other tree species. Received: 12 March 1997 / Accepted: 27 August 1997