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R Maron

Publications and source records attributed to R Maron.

12 recordsLinked to original sources
PubMed1979

Solubilization and reconstitution of the catecholamine transporter from bovine chromaffin granules.

The catecholamine transporter from bovine chromaffin granules has been solubilized by using low concentrations of sodium cholate in the presence of phospholipids. The functional solubilized protein has been incorporated into liposomes after removal of the detergent either by gel filtration or by dialysis. Reserpine-sensitive accumulation against a concentration gradient is achieved by artifically imposing a pH gradient across the membrane. In the reconstituted system adenosine 5'-triphosphate (ATP) serves as an energy source only at higher detergent concentrations. The proton-translocating adenosine triphosphatase (ATPase) is solubilized in parallel with the increasing efficiency of ATP as an energy source. Several criteria are proposed to distinguish between carrier-mediated (reserpine sensitive) and unmediated transport in the reconstituted system. The reserpine-sensitive process shows affinity and ss presented in this communication provide further support for the contention that concentrative uptake in biogenic amine storage vesicles is driven by a transmembrane pH gradient, which, in the native system, is generated by a proton-translocating ATPase. Moreover, the assays described provide a tool for the isolation and purification of the transport protein.

Adenosine Triphosphatases↗
PubMed1978

Higher antitumor efficacy of daunomycin when linked to dextran: in vivo and in vitro studies.

Daunomycin was coupled to dextrans of various molecular sizes. The binding to the dextran carriers augmented the therapeutic efficacy of the antitumor agent in a murine lymphoma line (YAC). When the treatment with the drug or its conjugates was given concomitantly with the tumor cells at separate sites, the unbound drug was able, at its optimally effective doses, to prevent tumors in 40% of the mice, whereas the drug-dextran was efficient in 80% of the mice. The advantage of the drug-dextran over the free drug was also manifested when the treatment was given 6 days after tumor transplantation. However, a further delay of the treatment resulted in a decrease in the potency of the drug-dextran. Similar behavior was observed when increasing tumor loads were transplanted (10(5)-10(8) cells) and when the treatment was administered immediately. The most favorable effect of the drug-dextran was obtained with 10(7) cells, but against 10(8) cells neither the free drug nor the bound one was effective.

Animals↗
PubMed1976

Fab dimers of antitumor immunoglobulins as covalent carriers of daunomycin.

Fab dimers were prepared by pepsin digestion from the immunoglobulin fraction of a rabbit antiserum towards the Yac Moloney virus lymphoma cells. Daunomycin was attatched to these (Fab)2 by covalent binding. The resultant conjugates exerted pharmacological toxic activity and specificity towards Yac target cells similar to that observed previously with conjugates of intact anti-Yac IgG. The activity was manifested both in vitro by inhibition of RNA synthesis and by the effect of reduction of the growth of the tumor cells in vivo after short exposure to the conjugates. The potential advantage of using an IgG molecule devoid of its Fc portion is discussed.

Animals↗
PubMed1975

The covalent binding of daunomycin and adriamycin to antibodies, with retention of both drug and antibody activities.

Daunomycin and adriamycin, two potent cancer chemotherapeutic agents, were linked to immunoglobulins, making use of various covalent cross-linking methods. The most suitable method for binding of the drugs to the antibodies, which retained both antibody and drug activity, was periodate oxidation of the drug, followed by the linking of the oxidized drug to the immunoglobulin and subsequent reduction of the product with sodium borohydride. The activity of the drug-antibody conjugates was tested in vitro on tumor and normal cell cultures and was found to be similar to that of the free drug. A significant amount of antibody activity was retained, as found both with anti-bovine serum albumin antibodies, assayed by chemically modified bacteriophage, and with anti-mouse tumor antibodies, assayed by C'-dependent cytotoxicity.

Animals↗
PubMed1975

The specific cytotoxic effects of daunomycin conjugated to antitumor antibodies.

Daunomycin was covalently bound to immunoglobulins by periodate oxidation as described in the preceding paper. Conjugates were prepared with immunoglobulins directed against either of two mouse lymphoid tumors or with nonspecific immunoglobulins. These conjugates were tested for their toxic effects on various tumor target cells as measured either by their inhibition of RNA synthesis or by their reduction of the growth of the tumor cells after transplantation. We found that the drug preferentially affected the target cells that the antibody to which it was attached could recognize. These daunomycin-antibody conjugates are therefore sufficiently toxic and selective in their effects to be potentially useful in in vivo therapeutic studies.

Animals↗
PubMedDate not supplied

The effect of a water soluble adjuvant on the immune response to synthetic polypeptides.

The effect of a water soluble adjuvant (WSA) extracted from mycobacteria on the immune response to synthetic polypeptides has been studied in rabbits and inbred mice. WSA increased the antibody response of rabbits to the synthetic polypeptide poly(Tyr,Glu)-poly(DLAla)--poly(Lys) designated (T,G)-A--L when injected together with either incomplete or complete Freund's adjuvants (FIA or FCA). As compared to the respective controls, the effect of WSA was more pronounced when injected with FIA. No detectable antibody titre was observed in rabbits immunized with (T,G)-A--L and WSA administered in an aqueous medium. WSA had no enhancing adjuvant effect on the antibody response of C3H.SW high responder mice to (T,G)-A--L when given either with FIA or with FCA. However, the antibody titres of C3H/HeJ and SJL low responder mice to (T,G)-A--L were increased by WSA when injected in combination with FIA or FCA. The immune responses of mice to two other synthetic polypeptides poly(Phe,Glu)-poly(DLAla)--poly(Lys), designated (Phe,G)-A--L, and poly-(Tyr,Glu)-poly(Pro)--poly(Lys), designated (T,G)-Pro--L, were not affected by the addition of WSA. Thus, WSA "corrects" selectively the genetic defect of low responder mice to synthetic antigens.

Adjuvants, Immunologic↗