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Synthesis of (+/-)-Deplancheine
The indole alkaloid (+)deplancheine (1) has been synthesized utilizing the intermediate
3-acatyl-1,2,6.7,12,12b-hexahydroindolo[2,3-a_kuinolizine (6) prepared in two synthetic steps from
readily available startlng materials
Cooperation between cdlg(leu-llb)+ nk cells and hla-dr+ cells in natural killing of herpesvirus-infected fibroblasts
We reported previously that natural killer (NK)
cell-mediated lysis of cytomegalovirus-infected targets
requires the presenceo f HLA-DR+ nonadherent
peripheral blood mononuclearc ells (NPBMC). In the
present study we determined whether NK cell-mediated
lysis of other herpesvirus-infected targets
also requires HLA-DR+ cells. Depletion of either
cluster designation (CD)16+ NK cells or HLA-DR+
cells from NPBMC significantly reduced their ability
to lyse herpes simplex virus (HSV)- and varicellazoster
virus (VZV)-infected fibroblasts. When CD16-
and HLA-DR- populations were mixedl,y sis of both
HSV- and VZV-infected targets was virtually completely
restored, indicating thaNt K cells and HLADR+
cells were required for lysis to occur. Cell-free
supernatants, obtained by incubating NPBMC or
CD16- cells with HSV- or VZV-infected targets, contained
antiviral activity and stimulated HLA-DRcells
to mediate lysis of corresponding virus-infected
targets. The addition of anti-interferon-a to
supernatants abolished their ability to stimulate
lysis. Thus, secretion of interferon-a by HLA-DR+
cells contributes to NK cell-mediated lysis of herpesvirus-
infected target
In Vitro and In Vivo Effect of Chloropromazine, Imipramine and Lithium Chloride on Monoamine Oxidase Activity in Rat Brain Mitochondria
Chloropromazine (CPZ) and imipramine at a concentration of 1 x 10- 3 M inhibit rat
brain mitochondrial monoamine oxidase activity in vitro by 70 and 55 % respectively,
'while lithium, even at a concentration of 0.05 M, inhibits the activity of this enzyme
'very negligibly (4%). In vivo, these drugs at a dose level of 56 mg CPZ, 76 mg
Jimipramine and 76 mg lithium chloride/Kg body wt., did not cause any observable
'variation from normal in brain mitochondrial monoamine oxidase activity
In Vitro and In Vivo Effect of Organophosphate Pesticides on Monoamine Oxidase Activity in Rat Brain
The effects of some organophosphate pesticides, e.g. lebaycid, metacid and metasystox
on the monoamine oxidase (MAO) activity in rat brain mitochondria have been
studied. These pesticides cause significant inhibition of MAO activity in vitro but have
negligible effects on its activity in vivo
Plant glycosides in a liposomal drug-delivery system
Plant glycosides were incorporated into the liposomal surface to study their sugar-specific uptake by various
tissues. Two steroid glycosides, namely floribundasaponin D, with rhamnose as terminal sugar, and gracillin, with glucose and rhamnose as end sugars, were selected for the purpose. '25I-human IgG encapsulated liposomes composed of egg lecithin (phosphatidylcholine), cholesterol, dicetyl phosphate (optional) and either floribundasaponin D or gracillin, when injected into the tail vein of rat, showed
significantly higher uptake in the rat liver than in appropriate controls. Whereas the uptake of
floribundasaponin D liposomes was observed to be non-specific, the increased uptake of the gracillin
liposomes, as judged from the inhibition studies with asppropriate sugars, was specific for glucose, although
the receptor was unable to distinguish between the a and /, anomers ('anomerically blind'). The liverperfusion
studies showed that the uptake of gracillin liposomes was mostly by non-parenchymal cells
Interleukin 2 enhances natural killing of varicella-zoster virus-infected targets
Preincubation of peripheral blood non-adherent mononuclear cells with purified or
recombinant interleukin 2 (IL-2) significantly enhanced natural killer (NK) activity
against uninfected and varicella-zoster virus (VZV)-infected targets, while antibodydependent
cellular cytotoxicity (ADCC) against VZV-infected targets was not increased.
Preincubation of effector cells with IL-2 had no effect on conjugate formation, but lysis of
both targets was increased in single cell assays. IL-2-enhanced NK against VZV-infected
targets was independent of gamma-interferon (y-IFN) production
Requirement for hla-dr + accessory cells in natural killing of cytomegalovirus-infected fibroblasts
NK cells mediate spontaneous killing of tumor-derived cells, virus-infected cells, and certain normal cells (1, 2). This type of cytotoxicity does not require
presensitization of the donor. For example, PBMC of individuals who are seronegative or seropositive for a given virus are equally able to lyse targets
infected with that virus (3). Production of IFN by lymphocytes exposed to virusinfected target cells and subsequent stimulation of NK cells by IFN was originally
proposed as the mechanism by which NK cells preferentially lyse virus-infected cells compared with uninfected ones (4). A primary role for IFN was challenged, however, by several authors who described a lack of correlation between magnitude of lysis and amounts of IFN detected in supernatant fluids (5, 6), an almost normal capacity of effector cells from patients with reduced ability to
produce IFN to lyse virus-infected target cells (7), and the inability of anti-IFN antibodies when present during the NK assay to prevent lysis of virus-infected
cells (5, 6). The cells responsible for NK activity against normal and tumor-derived target cell lines were identified as a leukocyte subset, distinct from B and T cells and from myelomonocytic cells (2). This subset expresses the low-affinity Fc receptor (FcR) 1 for aggregated IgG (CD16 antigen), recognized by a series of mAbs (8). NK cells responsible for lysis of virus-infected target cells have not been fully identified. Fitzgerald et al. (9) reported that the NK cells able to lyse HSVinfected targets differed from those that lysed K562 cells, as treatment of PBMC
with an mAb to HLA-DR plus C reduced their ability to kill HSV-infected fibroblasts, but not K562 cells. These authors concluded that these NK cell subsets could be distinguished on the basis of surface expression of HLA-DR
antigen. However, few if any resting NK (CD16+) cells in healthy donors are HLA-DR + (10, 1 1), raising the possibility that in the experiments of Fitzgerald
et a]. (9), a HLA-DR +, non-NK cell population was depleted
Introduction of Bacterial Components in Postadsorbed Plasma During Adsorption With Staphylococcus aureus
In ritro plasma adsorption over either protein A-positive Staphylococcus aureus Cowan I (SAC) or
protein A-negative S. aureus Wood 46 (SAW) led to leaching of bacterial biomolecules in the
postadsorbed plasma. Presence of bacterial moieties was demonstrated in the postadsorbed plasma by
more than one method: (1) using radiolabeled bacteria for adsorption with plasma and detecting
radioactivity in the postadsorbed plasma, (2) gel filtration of pre- and post-adsorbed plasmas over
Sephadex C-200 column and detecting additional peak(s) in the postadsorbed plasma, and (3)
immunoelectrophoretic analysis of pre- and postadsorbed plasmas and their column fractions against
rabbit anti-SAC antisera and demonstrating new precipitin bands in postadsorbed plasmas. Using an
extracorporeal plasma adsorption procedure in mongrel dogs, with radiolabeled SAC as the adsorbent,
we have demonstrated the presence of radioactivity in both the adsorbed and filtered (0.2 wm) blood
entering into the body, and the adsorbed blood that passed out of the body to reenter into the
extracorporeal circuit. These data suggest that components of S. aureus origin enter into the host
circulation during both in virro and ex vivo plasma adsorption, although the exact nature of those
extracted staphylococcal components remains unknown. This observation is of much significance since
it can possibly help elucidate the mechanism of tumor regression observed following perfusion of
plasma over SAC or SAW, followed by its reinfusion to the host