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Chondropsin D (2), a new 37-membered-ring macrolide lactam, was isolated as a minor constituent of an aqueous extract of the marine sponge Chondropsis sp. This sponge sample had previously been the source of chondropsins A (1) and B, two novel polyketide-derived macrolides with potent cytotoxic activity. The structure of 2 was initially deduced from analysis of spectral data. This assignment was supported by the observation that chondropsin A (1), which contains a 35-membered macrocyclic ring, could be converted to chondropsin D (2) by a base-catalyzed intramolecular transesterification reaction. Rearrangement of the methylated derivative of chondropsin A (3) to the corresponding methylated analogue of chondropsin D (4) confirmed the structure of 2.

In an attempt to study the structural dependence of antimycobacterial activity of the guaianolide dehydrocostus lactone and its derivatives, m-chloroperoxybenzoic acid oxidations of dehydrocostus lactone (1a) were performed. Three new monoepoxides, one previously synthesized diepoxide, and two new diepoxides were obtained. Two of the monoepoxides are C-10 epimers (3a, 3b), while the 4(15)-monoepoxide (2) has the 4α-O-configuration. The known diepoxide (4a) contains a C-10 α-epoxide and a β-epoxide at C-4. The diepoxides 4b and 4c, each with a C-4 α-epoxy group, differ in the configuration of the epoxide ring at C-10. Allylic oxidation of dehydrocostus lactone (1a) with selenium dioxide/tert-butyl hydroperoxide afforded the known 3-epizaluzanin C (1b). The relative configurations of compounds 1b−4c were established by 1D and 2D NMR techniques (¹H, ¹³C, COSY, NOESY, HMQC, and HMBC) as well as comparison with literature data. The molecular structures of lactones 1b, 4a, and 4c were determined by single-crystal X-ray diffraction. In radiorespirometric bioassays against Mycobacterium tuberculosis and Mycobacterium avium, dehydrocostus lactone (1a) exhibited minimum inhibitory concentrations of 2 and 16 μg/mL, respectively. In contrast, its monoepoxides (2, 3a, and 3b) and diepoxides (4a−c), as well as its hydrogenated derivatives and other analogues (1b, 1c, 5, and 6), showed significantly lower activities against M. tuberculosis.

For a quantum system in which a continuous or quasi-continuous band of levels is excited by means of several dipole interaction channels, we develop a mathematical theory that simplifies the numerical solution of the Schrödinger equation. The theory allows time-varying electric fields (or electric-field envelopes). It also takes into account the exact shape of the band as well as the fact that different excitation channels see different band shapes. Accuracy of the results can be as high as desired. We show that the dephasing of the quasi-continuum probability amplitudes in the conventional continuum basis corresponds to the propagation of well-defined waves in the new basis that we introduce.

Straightforward discretization of the equations of motion of a quasi-continuum interacting with an electromagnetic field often leads to physical and numerical difficulties. We derive two distinct methods for reducing the number of energy levels that must be treated explicitly in such calculations. One of these applies to bands of quasi-continua with slowly decreasing shoulders; the other, to bands with rapidly decreasing shoulders.

We have investigated the effects of stimulated Brillouin scattering on a transparent, spherical bead with a radius of the order of 25 μm, the wavelength of the incident laser being ~1 μm. We have used a simple approach with intuitive appeal that displays the fundamental physics. We consider two cases: (a) neither the pump field nor the Stokes field is on a Mie resonance of the spherical transparent bead; (b) both the pump field and the Stokes field are resonant. We derive explicit expressions for the electromagnetic differential scattering cross sections, using the Lippman–Schwinger equation for scalar electromagnetic field equations. Mie theory is utilized to estimate the occurrence of Mie resonances as the size parameter x = 2πa/λ is varied. We give quantitative estimates of the fraction of droplets expected to shatter owing to resonant stimulated Brillouin scattering in a polydisperse distribution.

The existence of a cardiac carnitine binding protein was demonstrated using an in vitro binding assay. The binding activity was solubilized with Triton X-100 from the pellet following a 59,000 X g centrifugation of rat ventricular homogenates. Preincubation at temperatures above 40 degrees C or treatment with pronase significantly reduced the binding activity, suggesting that the activity was that of a protein. Cell fractionation studies suggested that the cardiac carnitine binding protein was associated with the plasma membrane fraction and that its activity was distinct from carnitine palmitoyl-transferase, carnitine acetyltransferase, and carnitine translocase. Optimal binding required 60 min of incubation at 25 degrees C. The binding of carnitine to the cardiac carnitine binding protein was saturable, and a dissociation constant of 0.7 microM for DL-carnitine was measured. L-Carnitine competed with DL-[methyl-3H]carnitine for competition by D-carnitine was much less effective. Binding was significantly inhibited when N-ethylmaleimide, iodoacetic acid, or mercuric chloride was present. Once DL-[3H]carnitine was bound to the cardiac carnitine binding protein, radioactivity could be dissociated by a variety of mild treatments including dialysis, overnight incubation at 4 degrees C, and application to a gel filtration column.

We consider a vector c-number Langevin equation describing a single mode of the radiation field under the influence of a quadratic nonlinear interaction. The nonlinearity of the interaction is found to give rise to a nonzero diffusion matrix, which may be non-positive-definite. Using this diffusion matrix, we derive and solve an equation for the variance matrix of the system. An analysis of the solution then yields information about the production and properties of squeezing. In particular, we find that pulsed pumping of the medium, as compared with continuous pumping, can significantly enhance the maximum level of squeezing. Finally, we delineate the role of the non-positive-definite diffusion matrix through a discussion of the physical source of squeezing.

Haemograms were determined for 90 Mystromys, 3-24 months of age, to establish normal values and to evaluate the influence of age and gender. Males over 6 months of age had higher red blood cell counts, packed cell volumes and haemoglobin levels than females of the same age. The haemograms of females 3-5 months old resembled those of males. Age and gender did not cause detectable differences in leucocyte numbers in animals over 6 months old.

The fluorinated pyrimidines 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodouracil (FIAU) and 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-methyluracil (FMAU) are highly effective inhibitors of herpesvirus infections in vitro and in vivo. This report is concerned with an evaluation of their activities in African green monkeys (Cercopithecus aethiops) infected with simian varicella virus, a herpesvirus closely related to human varicella-zoster virus. Oral or intravenous administration of FIAU at 50 mg/kg per day as divided doses beginning 48 h after virus inoculation prevented the development of evidences of clinical infection. Oral treatment with FIAU at 30 mg/kg per day deferred as late as 7 days after virus inoculation modified the course of the disease. When treatment was started 48 h after virus inoculation, daily doses of FIAU as small as 1 mg/kg inhibited development of infections; daily doses of 0.2 mg/kg were ineffective. At the latter dose FMAU prevented development of clinical disease, suggesting that it was more active than FIAU. No signs of FIAU toxicity were observed, with the single exception of an early but transitory elevation in aspartate aminotransferase activity in serum.

The cannabinoid receptor in brain (CB1) specifically binds delta 9-tetrahydrocannabinol, the predominant central nervous system-active component of marijuana. An eicosanoid found in brain, N-(2-hydroxyethyl)arachidonylamide (anandamide), binds to CB1 with similar affinity. This report considers structure-activity requirements for a series of novel amides and rigid hairpin conformations typified by N-(2-hydroxyethyl)prostaglandin amides, assayed with phenylmethylsulfonyl fluoride inactivation of esterases/amidases. Arachidonyl esters were 30-fold less potent than N-(2-hydroxyethyl)arachidonylamide, showing a rank order of potency of methyl = ethyl > propyl = isopropyl. Within the N-(hydroxyalkyl)arachidonylamide series, a one-carbon increase in chain length increased the potency 2-fold, but continued extension decreased affinity. Substituting the amide for the N-(2-hydroxyethyl)amide function produced a 4-fold loss of affinity. The N-(propyl)-, N-(butyl)-, and N-(benzyl)arachidonylamide derivatives exhibited a 3-fold increase, no change, and a 5-fold decrease, respectively, in affinity, compared with N-(2-hydroxyethyl)arachidonylamide. Both the methoxy ether and the formamide derivatives suffered > 20-fold loss of potency, compared with N-(2-hydroxyethyl)arachidonylamide. N-(2-Aminoethyl)arachidonylamide interacted poorly with CB1. At 100 microM, N-(2-hydroxyethyl)amide analogs of prostaglandin E2, A2, B2, and B1 failed to alter [3H]CP55940 binding to CB1. N-(2-Hydroxyethyl)arachidonylamide inhibited adenylate cyclase with lesser potency but with similar efficacy, compared with desacetyllevonantradol. Extending the length of the hydroxyalkyl moiety by one carbon increased the apparent potency by 1 order of magnitude. The N-(propyl) derivative exhibited a 5-fold greater potency than did the N-(2-hydroxyethyl) analog. It appears that the bulk and length of the moiety appended to arachidonic acid are more important determinants of affinity for CB1 than is hydrogen-bonding capability.

In a bioassay-guided search for antimycobacterial compounds from higher plants of the southeastern United States, we have chemically investigated the sea daisy (Borrichia frutescens) from coastal marshes of Louisiana for their active constituents. Bioactive chromatographic fractions provided two new triterpenes, (24R)-24,25-epoxycycloartan-3-one (1) and (23R)-3-oxolanosta-8,24-dien-23-ol (4), and (3αH,24R)-24,25-epoxycycloartan-3-ol (3a). Compound 3a had been previously isolated as a mixture of C-24 epimers. The structures of 1, 3a, and 4 were established by spectroscopic methods and chemical transformations, and the molecular structures of 1 and 4 were determined by single-crystal X-ray diffraction. In a radiorespirometric bioassay against Mycobacterium tuberculosis, the epoxycycloartanes 1 and 3a exhibited minimum inhibitory concentrations of 8 μg/mL. In contrast, the lanostadiene-type triterpene 4 showed no significant inhibition at 128 μg/mL, as did the acetate 3b. Cytotoxicity for Vero cells gave IC50 values of 71.8, 39.8, and 103.6 μg/mL for triterpenes 1, 3a, and 4, respectively.