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L Morrison

Publications and source records attributed to L Morrison.

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Role of C3 in the control of monocyte C2 production.

Serum-treated antigen-antibody complexes (IC) and DTSP-polymerized C3b and C3c inhibited the production of the second complement component (C2) by monocytes in culture, whereas monomeric C3, C3b, C3bi, C3c or C3d had no effect. The degree of inhibition of dithiobissuccinimidyl propionate (DTSP)-polymerized C3 was proportional to the degree of polymerization, dimer exhibiting less inhibitory activity than larger molecular weight polymers. The inhibitory effect of serum-treated IC and DTSP-polymerized C3b was abrogated by their pretreatment with Fab fragments of anti-C3, or pretreatment of monocytes with Fab fragments of antiserum to the C3b receptor (CR1). We have concluded that the inhibition of C2 production produced by serum-treated IC is due to bound C3b or C3bi, and is mediated by CR1. Furthermore cross linking of receptors is required for this effect; two or more than two receptors must be cross-linked for a significant effect to be observed.

Antigen-Antibody Complex

Phagocytosis inhibits the production of C2 by human monocytes.

Production of the second complement component by cultured human monocytes was suppressed by the addition of a variety of phagocytosable particles. The degree of suppression was related to the concentration of particles, but was unrelated to particle size, the presence of surface sialic acid, antibody or C3b. The failure to reverse suppression by prostaglandin synthetase inhibitors indicates that it is not mediated by prostaglandins.

Cells, Cultured

Reversal of povidone-iodine-induced suppressor cell activity by sodium borohydride.

We have confirmed the generation of suppressor cells as the result of lymphocyte exposure to Betadine, a topical bacteriocide in common clinical use. Suppressor cell induction is the result of cell surface changes which we found to be completely reversible by the action of the reducing agent, sodium borohydride. These findings are important clinically, particularly as they relate to burn patients who often accumulate iodine concentrations sufficient to depress immune responsiveness. Our results suggest that suppressor cell development resulting from Betadine treatment is reversible. Experimental burn treatment procedures could easily be modified to include procedures to abolish such suppressor cell activity.

Borohydrides

Mechanism of melphalan resistance developed in vitro in human melanoma cells.

Melphalan resistance developed previously in a human melanoma cell line (MM253) could not be further increased. Cross-resistance was found to nitrogen mustard but not to ultraviolet light radiation. A clone of MM253 had the same drug sensitivity and heterogeneous chromosome complements as did the parent culture. The melphalan-resistant cells (MM253-12M) had 2.6-fold the D0, 1.5-fold the size, 1.3-fold the RNA content, 1.4-fold the protein content, and 2.6-fold the DNA content of the sensitive parent line. There was no evidence for activation or detoxification of melphalan by intact melanoma cells or by mouse liver microsomes competent for the activation of other drugs. Melphalan transport was similar in both cell lines, reaching a steady-state level 3 times the concentration in the medium after 2.5 min. Both lines covalently bound the same total amount of [3H]melphalan per cell, but in MM253-12M a 50% decrease in binding to DNA was almost sufficient to account for the increase in resistance. The level of melphalan-induced DNA interstrand cross-links, which were heat labile but not alkali labile, reached a maximum during the 4-hr treatment period and then declined slowly. The degree of cross-linking in MM253-12M was 50% less than that in MM253. Unlike ultraviolet light, methyl methanesulfonate, and nitrogen mustard, melphalan at equitoxic doses did not damage the DNA sufficiently to immediately inhibit DNA synthesis. Although both lines were proficient for repair of ultraviolet light and methyl methane sulfonate damage, melphalan did not induce significant levels of DNA repair synthesis and had little effect on the rate of DNA chain elongation. In MM253 cells, strand breaks were detected only at high melphalan doses; MM253-12M formed breaks more readily. This evidence suggests that the cross-linking events and that developed resistance arises from decreased susceptibility to DNA to this damage.

Biological Transport

Poisoning and enuresis.

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Antidepressive Agents, Tricyclic

Human malignant melanoma cell lines.

A series of 10 cell lines established from human malignant melanomas is described. The morphology varied but, in general, was epithelioid. Five produced visible melanin in culture but others produced melanin precursors. All lines were aneuploid and each had a distinctive human karyotype. One line appeared not to have the same sex as the patient but its karyotype was distinct from that of other lines.

Aneuploidy

Melphalan-induced chromosome damage in sensitive and resistant human melanoma cell lines.

Twelve consecutive treatments of a human melanoma cell line (MM253) with melphalan gave a subline (MM253-12M) which was five times more resistant to melphalan with respect to survival. In contrast to mustard-resistant rodent cells, the MM253-12M line had a higher stemline number than the parent line while growth rate and cell and colony morphology were unchanged. A further melphalan treatment following attempted mutagenesis with UV did not increase resistance. In a comparison of these two lines with two melanoma lines derived from other patients and the rat XC line, resistance was correlated with lower frequency of melphalan-induced chromosome aberrations, determined 48 h after a 4-h exposure to melphalan (3 microgram/ml). In the two cell lines studied, aberration-free metaphase cells from treated culture had fewer chromosomes than untreated cells. DNA synthesis studied in the 4- to 72-h period after treatment was inhibited to the same extent in MM253 and MM253-12M cells at 4 microgram/ml but to a greater extent in the sensitive line at 0.1-1.5 microgram/ml. During the first hour of treatment at 0.1-1.5 microgram/ml, DNA synthesis in MM253 appeared to be enhanced.

Cell Line

Maternal and fetal cellular relationships in the human placental basal plate.

Maternal and fetal cellular relationships in the normal human term placental basal plate were investigated by single and double immunohistochemical labelling techniques. Extravillous fetal trophoblast in the basal plate was uniformly reactive with markers of low-molecular-weight cytokeratins. The predominant maternal leucocyte population in the basal plate consisted of leucocyte-common-antigen-positive, class II MHC-positive macrophages, which exhibited acid phosphatase activity. Double-labelling methods highlighted the close association of these macrophages with extravillous trophoblast: they often extended processes around the fetal cells and were also observed within islands of cytotrophoblast. Other leucocytes were uncommon, although aggregates of T cells were apparent in some tissues.

Antibodies, Monoclonal

Immunohistochemical localization of interferons in human placental tissues in normal, ectopic, and molar pregnancy.

Interferon (IFN)alpha, beta, and gamma have been localized in normal and pathological human pregnancy using both polyclonal and monoclonal antibodies in immunohistochemical techniques. IFN alpha was localized to fetal chorionic villous syncytiotrophoblast throughout normal pregnancy, as well as to extravillous trophoblast in the placental bed and chorion lave. Maternal decidual leukocytes, as well as fetal Hofbauer cells in the villous mesenchyme, also contained IFN alpha, IFN gamma was detected in villous syncytiotrophoblast, while anti-IFN beta showed only patchy weak reactivity with syncytiotrophoblast. Reaction patterns on ectopic pregnancy tissues were similar to those in early intrauterine pregnancy. In molar pregnancy, reactivity for IFN alpha, beta, and gamma was observed in syncytiotrophoblast. Along with their potential anti-viral effects, placental interferons could play a role in local immunomodulation or in regulation of embryonic cell proliferation and differentiation.

Antibodies, Monoclonal