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Biomedical subjects

B Schechter

Publications and source records attributed to B Schechter.

At least 37 records · Page 2Linked to original sources

A comparison of motility: autogenous dermis-fat vs synthetic spherical implants.

The socket and prosthesis motility and the forniceal depths in a group of 47 patients who had undergone enucleation and implantation of synthetic spherical implants were compared with those in a group of 34 patients who had undergone enucleation and implantation of autogenous dermis-fat orbital implants. The primary autogenous dermis-fat orbital implants provided greater socket movement and deeper fornices than the synthetic spherical implants. Prosthesis motility, however, was the same in the two groups.

Adipose Tissue↗

Increased therapeutic efficacy of cis-platinum complexes of poly-L-glutamic acid against a murine carcinoma.

Cis-diamminedichloroplatinum(II) (cis-DDP) and cis diamminediaquoplatinum(II) nitrate (cis-aq) were complexed to poly-L-glutamic acid (PG) of Mr 13,000 or 58,000. Soluble complexes were formed by mixing the platinum(II) compounds with the PG preparations in water at a molar ratio of one platinum(II) to 5 glutamyl residues of the PG. Compared to free cis-DDP, the complexes were about 2 to 6 times less cytotoxic to F9 embryonal carcinoma cells in vitro. In vivo studies with this tumor indicated that when administered i.p. one day after the tumor cells, the complexes were somewhat less active than cis-DDP. However, in comparison to the free drug which, due to its toxicity, was effective only within a very narrow dose range, the complexes were much less toxic, manifesting a wide therapeutic range in which no mortality occurred either from the tumor or as a result of the toxic effects of the drug. Cis-DDP and cis-aq complexes of PG Mr-58,000 were somewhat more toxic than the complexes of PG Mr, 13,000. The in vivo anti-tumor activity of most complexes was superior to that of free cis-DDP when tested in mice carrying high tumor loads. Due to their wide therapeutic range, the complexes could be given at high drug doses resulting in increased life span of the tumor-bearing mice. Moreover, 3 repeated injections of these high doses did not cause death from toxicity and resulted in partial or total eradication of advanced tumors.

Animals↗

Selective cytotoxicity against tumor cells by cisplatin complexed to antitumor antibodies via carboxymethyl dextran.

Cis-diamminedichloroplatinum (II) (cis-DDP) and its structural analogue cis-diamminediaquoplatinum(II) nitrate (cis-aq) were complexed via an intermediate dextran carrier to antibodies specifically reactive with B lymphoma cells (38C-13). The potential use of these drugs in site-directed immunotargeting was evaluated. The two platinum(II) compounds were previously shown to form pharmacologically active complexes with carboxymethyl dextran (CM-dex). For the purpose of preparing drug-antibody complexes, CM-dex was first conjugated to idiotypic antibodies that recognize a specific membrane IgM on the B lymphoma cells. The conjugates were prepared by a modified water-soluble carbodiimide method in which N-hydroxysuccinimide was used to enhance the coupling reaction. The conjugation was followed by separation of the CM-dex-IgG conjugates from unconjugated CM-dex or IgG. The platinum(II) compounds were then complexed to the CM-dex-IgG resulting in complexes carrying up to 50 mole drug/mole IgG. Both cis-DDP and cis-aq complexes of CM-dex-antibody conjugates maintained most of the original cell-binding activity of the antibodies. An in vitro assay was used to demonstrate selective binding to tumor cells in which the target cells were treated with specific immune complexes and washed before culture. In this assay the specific complexes showed preferential cytotoxicity for the B lymphoma cells in comparison to the free drugs, drug CM-dex, or nonspecific immune complexes.

Animals↗

Cis-platinum(II) complexes of carboxymethyl-dextran as potential antitumor agents. I. Preparation and characterization.

Cis-diamminedichloro platinum (II) (cis-DDP) and cis-diamminediaquo platinum (II) nitrate (cis-aq) were demonstrated to form complexes with dextran (dex) substituted with carboxymethyl (CM) groups at an average substitution ratio of 1 mole CM per 2 mole glucose units of dextran. The complexes were formed by reacting each of the two platinum (II) derivatives with carboxymethyl-dextran (CM-dex) at room temperature (RT) or at 37 degrees C in an aqueous solution. The complexing rate depended on temperature, ratio of platinum (II) compounds to CM-dex in the reaction mixture, and time of reaction. Experiments were performed with two CM-dex preparations, derived from dex T-10 (Mr-10,000) and from dex T-40 (Mr-40,000). Soluble cis-DDP and cis-aq complexes formed with CM-dex T-10 and CM-dex T-40 could carry up to 15 mole or 60 mole of the platinum (II) compounds per 1 mole CM-dex, respectively but higher complexing ratios resulted in complex precipitation. Reactivity of cis-aq with CM-dex was higher than that of cis-DDP. NaCl interfered with complex formation, but did not cause dissociation of already formed complexes. The binding of cis-DDP and cis-aq to CM-dex is, however, reversible since the drugs could be exchanged by other acceptors of higher affinity to platinum (II) such as O-phyenlenediamine, or DNA.

Antineoplastic Agents↗

Cis-platinum (II) complexes of carboxymethyl-dextran as potential antitumor agents. II. In vitro and in vivo activity.

Cis-diamminedichloro platinum (II) (cis-DDP) and cis-diamminediaquo platinum (II) nitrate (cis-aq) were complexed to a macromolecular carrier carboxymethyl dextran (CM-dex). Two carriers were used in this study, one derived from dex-T-10 (Mr-10000) and the other from dex-T-40 (Mr-40000). The two platinum (II) drugs formed soluble complexes with both carriers. Uncomplexed and complexed drugs were tested and found to be cytotoxic in vitro against 5 murine and 2 human derived tumor cell lines. The two free platinum (II) drugs were cytotoxic against these cells to a similar extent. In comparison to the free drugs the complexes were somewhat less active, up to 3 fold, against murine 38C-13, L1210, EL-4 and RDM-4 leukemias, as well as against human HeLa and osteogenic sarcoma, and as active as the free drugs against murine F9 embryonal carcinoma. There were no major differences in the in vitro cytotoxic activity between CM-dex T-10 and CM-dex T-40 complexes. Differences due to the molecular size of the carrier were observed in vivo: The CM-dex T-10 complexes were significantly less toxic than the free drugs, whereas the reduction of toxicity by complexing to CM-dex T-40 was less profound. As for the efficacy, when tested in vivo against a cis-DDP sensitive tumor (F9) the T-40 complexes were equally or even more effective than the respective free drugs. The T-10 complexes were less effective than the free drugs at equal drug doses but their effectivity increased at increasing drug levels. These complexes were, however, very effective in inhibiting tumor growth upon repeated injections, leading to 100% survival.

Animals↗

Enrichment of suppressor cell activity by hydrocortisone: suppression of in vitro activation of splenocytes from mice bearing Lewis lung carcinoma.

Suppressor cells in spleens of mice bearing the Lewis lung carcinoma (3LL) suppressed the anti-tumor immune response in vivo but not in vitro. The hydrocortisone (HC)-resistant fraction of spleen cells from tumor-bearing mice (TBM) was, on the other hand, suppressive in vitro, due to enrichment for HC-resistant suppressor cells. This cellular fraction suppressed the tumor-induced differentiation of memory cells as well as the tumor-independent in vitro activation of TBM spleen cells. The in vitro lymphoproliferative response of TBM spleen cells to mitogens was also subjected to suppression: these cells showed a lower response to a mitogen such as Concanavalin A (Con A) and were capable of suppressing the response of normal spleen cells to this mitogen. HC treatment of TBM 2 days prior to spleen harvest enriched the splenic population for suppressor cells that suppressed Con A-induced activation.

Animals↗

Binding of anti-tumor immunoglobulins and their daunomycin conjugates to the tumor and its metastase. In vitro and in vivo studies with Lewis lung carcinoma.

The present study was undertaken in order to evaluate the possibility of using anti-tumor antibodies as specific carriers of chemotherapeutic drugs to tumor metastases. Xenogeneic and syngeneic antisera were prepared against a metastasizing C57BL tumor, the Lewis lung carcinoma (3LL). The binding of absorbed xenogeneic and syngeneic anti-3LL sera or their Ig fractions to 3LL tumor cells was assayed by direct and indirect methods. Antisera prepared against tumor cells from a local growth reacted to a similar extent with those obtained from the lung metastases. Radioiodinated immunoglobulins from syngeneic antisera injected into mice bearing metastases localized preferentially in metastasis-bearing lungs as compared to several other organs tested. No such preferential uptake was observed either in mice bearing metastases injected with iodinated normal Ig or in normal mice injected with iodinated anti-3LL Ig. This relative accumulation in the metastasis-bearing lungs was observed 3-4 days after the inoculation, when the whole Ig fraction was used, whereas a specific antibody-enriched preparation localized as early as 24 h after injection. Daunomycin--anti-3LL-Ig conjugates were effective inhibitors of tumor cells from both local and the metastatic growths. They were more active than either the free drug or drug conjugates of normal Ig, in in vitro assays.

Animals↗

Suppressor cells prevent host resistance to tumor growth.

The role of immunosuppressor cells in preventing host immune rejection of tumor cells is described. The growth of Lewis lung carcinoma (3LL) in syngeneic C57BL mice is accompanied by a weak and transient anti-tumor cytotoxic response that is later on replaced by tumor-enhancing activity. This enhancing activity is correlated with the generation of suppressor cells in 3LL-bearing mice. Such suppressors were demonstrated in two ways: (a) Elimination of the hydrocortisone(HC)-sensitive lymphoid population from tumor-bearing mice (TBM) resulted in a significant increase in the anti-tumor cytotoxic response and in a marked delay in tumor development. It is assumed that HC inactivates precursors of suppressor lymphocytes whereas the mature suppressor cells themselves are HC-resistant. (b) The increased resistance against the tumor could be partially re-suppressed by restoring the HC-treated TBM with spleen or thymus cells from normal C57BL. Suppression, however, was more pronounced if the resistant mice were restored with spleen or thymus cells from TBM. HC-resistant spleen cells from TBM that appear to be enriched for mature suppressor cells were capable of suppressing in vitro the secondary sensitization of spleen cells from TBM against tumor cells.

Animals↗

Generation of suppressor lymphocytes during sensitization in culture against a syngeneic tumor: affinity chromatography on insolubilized histamine.

We investigated the effect of depletion of histamine-binding lymphoid cells on immunological properties of lymphocytes sensitized in culture against tumor cells. C57BL/6 spleen cells that were sensitized in vitro on monolayers of the syngeneic Lewis lung carcinoma (3LL) became cytotoxic to the tumor cells in vitro after 3 to 5 days of sensitization. Sensitized cells harvested after 4 days of sensitization occasionally enhanced tumor growth in vivo. Fractionation of the sensitized lymphocytes over insolubilized histamine-rabbit serum albumin-Sepharose (HRS) columns decreased or abolished the enhancing activity in vivo and specifically increased the in vitro cytotoxic activity of the depleted lymphocytes. A similar increase in the cytotoxic activity of HRS-fractionated cells was observed in an allogeneic combination of C57BL spleen cells sensitized against C3H fibroblasts. The effect of HRS chromatography on the in vitro cytotoxic activity increased with prolonged incubation of the depleted effector cells with the target cells.

Animals↗

Enhancing lymphocytes in spleens of tumor-bearing mice: affinity chromatography on insolubilized histamine.

Spleen cells from C57BL mice carrying the metastatic Lewis lung carcinoma (3LL) developed a transient cytotoxic response towards the tumor shortly after tumor transplantation. Later on, the cytotoxic activity was lost and enhancing lymphocytes could be demonstrated in the spleens of the tumor-bearing mice (TBM). Spleen cells that were transferred together with tumor cells into syngeneic recipients enhanced tumor growth. The enhancing activity could be eliminated by the removal of a cell population that bound to histamine/rabbit serum albumin/Sepharose (HRS). The adherent population was enriched for enhancing lymphocytes, since it enhanced tumor growth more than the unfractionated population. The non-adherent cells, on the other hand, lost their enhancing activity in vivo and were sometimes protective against tumor growth. In addition, these cells manifested in vitro cytotoxicity against tumor cells. Hence the suppression of the cytotoxic expression in TBM is, at least in part, due to suppressor lymphocytes that bind to unsolubilized histamine. These cells seem to enhance tumor growth by suppressing host reactivity. Thus the enhancing lymphocyte populations can be separated into two subpopulations, of which one is enriched while the other is depleted of suppressor cells.

Animals↗

Cellular immunity in newborn infants and children: stimulation of lymphocyte protein synthesis as a measure of immune competence.

An assay based on the early stimulation of protein synthesis in lymphocytes has been used as an in vitro measure of cellular immune competence. 3H-labelled leucine incorporation into human peripheral lymphocytes (PBL) stimulated by the mitogens phytohaemagglutinin (PHA), wax bean agglutinin (WBA) and Concanavalin A (Con A) was measured after one day in culture. This assay offers a technical advantage over the analogous 3H-labelled thymidine incorporation assay, because of the short incubation time required and the absence of homologous serum in the assay system. Newborn infants and patients with Down's syndrome as a group had normal responses, whereas those suffering from recurrent infections demonstrated normal or hyper-reactive responses. Patients with lymphoproliferative disorders, ataxia telangiectasia, and some patients under steroid therapy had diminished immune proliferative reactions. These results are in agreement with most previously reported studies using other assay systems.

Adolescent↗

A pre-formed methyl methacrylate cranioplasty.

The use of a pre-formed methyl methacrylate cranioplasty prosthesis reinforced with stainless steel wire is described. The prosthesis is non-reactive, virtually unbreakable, and undentable. Pre-forming of the prosthesis in the dental laboratory using a mold of the patient's bony defect as a model saves considerable operating time, and when employed for a large cranial defect the three dimensional cosmetic effect is superior to intra-operatively fashioned prostheses.

Biocompatible Materials↗