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Effect of Erythropoietin on the Glucose Transport of Rat Etythrocytes and Bone Marrow Cells
Modern studies on the structure of membranes have revealed that chain length
and extent of saturation of fatty acids of phospholipids influence membrane
permeability (1). Differences in permeabilities of glycerol, erythritol, urea, and
anions have been reported to be related to the membrane phospholipids (2).
Erythrocyte membrane permeability increases with a rise in phosphatidylcholine
content of the membrane lipids (3). These results suggest that the lipid environment
of the membrane transport proteins can affect transmembrane fluxes in erythrocytes.
Erythrocytes of different species which differ in lipid composition, particularly
having loosely bound phospholipids, exhibited a marked difference in their
permeability characteristics (4). In short, phospholipids in biological membranes
have been shown to modulate the permeability behavior of the erythrocyte membrane.
The role of erythropoietin (Ep) on the erythrocyte membrane is quite
clear from our recent studies (5-8). We have demonstrated that Ep not only
stimulates [14C]acetate incorporation into membrane lipids (6) but also alters the
fatty acid composition of the erythrocyte membrane as well as the ratio of
saturated to unsaturated fatty acids (7). This hormone also has an influence on
the exchange of cholesterol and phospholipid between erythrocyte and plasma
(8). In view of the above observations we were interested in studying the effect
of this hormone on the permeability of glucose in erythrocytes
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
The Effect of Surface-Coupled Antigen of Liposomes in Immunopotentiation
The effect of surface coupled antigens of liposomes
on the immunological response has been investigated.
Lysozyme was covalently coupled to
neutral and positively charged liposomes using
glutaraldehyde. Subcutaneous administration of
these preparations stimulated a significant antibody
response higher than that elicited by the antigen
entrapped in neutral liposomes. Immunization
by liposomal antigens together with complete
Freund’s adjuvant resulted in strong immune
responses, highest with the antigen coupled to neutral
and positively charged liposomes followed by
the antigen entrapped in neutral liposomes.
Primary and secondary immunization with lysozyme,
both entrapped and coupled to liposomes,
evoked an IgG response
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
Liposome as an Adjuvant for the Production of Estradiol Antibodies
Mice immunized with liposome associated
estradiol-bovine serum albumin conjugate
(E2-BSA) showed a significantly higher estradiolspecific
immune response than did mice injected
with the free conjugate. The conjugation of estradiol
with BSA is imperative, since injection of liposomes
with estradiol in the lipid bilayer was found
to be ineffective in inducing an immune response.
Entrapment of E2-BSA in neutral and positively
charged liposomes was found to be a potent mode
of immunostimulation, even better than emulsification
in complete Freund's adjuvant (CFA). Covalent
liposome surface association of E2-BSA induced
a good immunopotentiation. However, the
response was lower than that observed with the entrapped
conjugate. The affinity and the specificity
of antisera, raised in different ways, were determined
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
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
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