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Biomedical subjects

P D Cooper

Publications and source records attributed to P D Cooper.

At least 37 records · Page 2Linked to original sources
PubMed1991

The adjuvanticity of Algammulin, a new vaccine adjuvant.

Algammulin is a suspension of 1-2 microns ovoids of the immune stimulant gamma inulin (g-IN) in which alum is embedded as a carrier for protein or other anionic antigens. Tests for specific IgG and seroconversion responses in mice immunized with keyhole limpet haemocyanin (KLH) show that the presence of g-IN on the alum has increased its adjuvanticity 6- to 17-fold (p less than 0.001), and thus has a synergistic effect. A mixture of alum and g-IN was no more active than alum alone. Low KLH doses at borderline seroconversion levels (0.1-1 microgram/mouse) allow comparison with a vaccine situation. The improved Algammulin responses extended to 58 days after primary doses and to memory recall after boost at 65 days. At 1 mg Algammulin i.p. in primary and secondary doses the anti-KLH IgG responses were equal to those from Freund's complete adjuvant. The g-IN on the alum increased all responses tested (IgG 1, 2a, 2b, 3 and total IgG, IgM, IgA and IgE), but changed the emphasis from that of alum (favouring mostly IgG 2a, IgG 2b and IgA).

Adjuvants, Immunologic↗
PubMed1988

Development and morphology of the sternal foramen.

Bony defects (foramina) in the sternum were found in 6.7% of a large contemporary autopsy population. Usually solitary and located in the body of the sternum, these defects rarely occur multiply and in the manubrium. They have been found in children as young as 8 years as well as in persons of advanced age. Multiple mesosternal foramina and a manubrial foramen are described here for the first time. Sternal foramina form along lines of fusion of multiple centers of ossification and are the result of incomplete fusion. They have been misinterpreted as acquired lesions, usually gunshot wounds.

Autopsy↗
PubMed1986

Anti-complementary action of polymorphic "solubility forms" of particulate inulin.

Inulin crystallizes in a series of polymorphic forms with different solubility rates, ranging from one instantly soluble at 23 degrees C (beta 0(23) inulin) through a form soluble at 37 degrees C with a half-time of 8 min (alpha 8(37) inulin) to a form virtually insoluble at 37 degrees C (gamma inulin). All forms are interconvertible, the more soluble and unstable progressing on standing to less soluble and more stable forms, only reversible by complete solution followed by recrystallization. The end product is the stable gamma inulin, only formed by polymers greater than 8000 mol. wt. A method is given for preparing pure "gamma inulin for injection", comprising insoluble ovoids of less than 1 micron diameter free of soluble inulin and endotoxin. An assay developed for complement action by the alternative pathway showed that gamma inulin was the most potent activator polymorph, more active than killed S. aureus and zymosan. Dissolved inulin and the more soluble polymorphs were inactive and in a mixture hindered alternative pathway activation by the gamma form.

Chromatography, DEAE-Cellulose↗
PubMed1986

The anti-melanoma activity of inulin in mice.

Finely divided, insoluble inulin (gamma polymorph), given intraperitoneally (i.p.) to C57BL mice 1-3 days after i.p. B16 melanoma cells, very significantly increased their mean survival time (MST) in low doses (less than or equal to 40 and less than or equal to 100 micrograms/mouse in 50 and 80% of tests, respectively). The gamma inulin was pure and free of endotoxin and soluble inulin, and was developed as a potent reagent specific for activating the alternative pathway of complement (APC). Its antitumour action paralleled its in vitro APC activation, namely, both activities were sharply dose-dependent up to a threshold dose above which they were dose-independent; dissolved inulin was inactive in vitro and in vivo, decreased the MST of the mice and in a mixture antagonized the in vitro and in vivo activities of gamma inulin; the more soluble (alpha) polymorphs were active in proportion to their gamma content but the effects were blocked at higher doses presumably by dissolved inulin. In addition, depletion of host APC with cobra venom factor or inulin before giving B16 cells increased their malignancy and abrogated the subsequent antitumour action of gamma inulin. The minimum i.p. dose of gamma inulin found to activate serum APC in vivo was 50 micrograms (2.5 mg/kg), i.e. close to the minimum antitumour dose. These close correlations and the specificity of the reagent indicate that activation in vivo of the APC (cellular or humoral) is an important first contact in stimulating host antitumour defences in this mouse model.

Animals↗
PubMed1985

Complement and cancer: activation of the alternative pathway as a theoretical base for immunotherapy.

Activation of the APC is pointed out as the common factor in all sufficiently studied cancer treatments employing nonspecific, active immunotherapy. This chapter outlines the molecular biology of both APC and classical pathway of complement, summarizes the alternative pathway's biologic activities especially in relation to the C3/C5 convertase C3b,Bb, and its implications in the mechanism of host defense against malignancies, particularly relating to the activated macrophage. The many involvements of the APC in the various agents used for nonspecific active immunotherapy are reviewed, and possible clinical implications outlined. It is concluded that activation of the APC can be proposed as the specific theoretical basis so far lacking for this treatment modality and that it is accordingly feasible to attempt to monitor clinical application of this principle by fine-tuning of APC activation in cases of human cancer.

Adjuvants, Immunologic↗
PubMed1985

Chloride transport across the integumentary epithelium of Manduca sexta (Lepidoptera: Sphingidae).

Moulting fluid of Manduca sexta contains high concentrations of potassium and bicarbonate (100 mM) and low concentrations of chloride (5 mM). This fluid begins to disappear from the exuvial space approximately 9-10 h before the actual shedding of the integument. During this time, the integument can be isolated in an Ussing cell and electrical properties measured in vitro. In a normal 32 mM KHCO3 saline, potential difference (PD) is around 10 mV, exuvial side positive, and short-circuit current (SCC) is 15-20 microA cm-2. Substitution of chloride slightly reduces both PD and SCC, although resistance does not change significantly. Measurement of chloride transport in the absence of K+ indicates that 100% of the SCC can be accounted for by the net chloride flux (approximately 2 microA cm-2). The Km and Jmax for transepithelial chloride transport are 14 mM and 0.1 microEq cm-2 h-1. Bilateral potassium addition stimulates chloride transport, doubling net chloride flux as potassium concentration increases from 2 to 5 mM. Chloride net flux is not inhibited by the presence of furosemide (1 mM), nor in HCO3- -free saline by thiocyanate (1 or 10 mM) or acetazolamide (0.1 mM), but is inhibited by 100% N2. The pattern of chloride transport in M. sexta is similar to that previously reported for the rectum of locusts. As chloride is normally at low concentrations in the moulting fluid, it is suggested that this transport system acts to maintain low intracellular concentrations which may be necessary for enzymatic functions in the epidermal cells and has little importance in fluid transport.

Animals↗
PubMed1984

Substances that can trigger activation of the alternative pathway of complement have anti-melanoma activity in mice.

Intraperitoneal (i.p.) injection of substances that can ignite the alternative pathway of complement, namely isolated human C3b or C3(H2O), guinea-pig C3(H2O) or cobra venom factor, or conventionally prepared zymosan, will reproducibly and very significantly increase the mean survival time of C57BL mice previously inoculated i.p. with melanoma cells. The effect is greater at higher doses and earlier post-inoculation (p.i.) administration, but the substances are active at low doses (30-100 micrograms/mouse) if given early enough. It is likely that C3b or C3(H2O) was the previously unidentified anti-tumour factor activated in serum by S. aureus treatment or serum fractionation and described elsewhere. Activation of the alternative pathway of complement appears to have potential interest for cancer therapy.

Animals↗
PubMed1983

Protein A treatment of cancer: activation of a serum component with trans-species anti-B16 melanoma activity.

Mice (C57BL) succumbed to cultured B16 melanoma cells i.p. with reproducible kinetics and an MST2 of about 26 days. Serum from tumour-bearing or normal mice was treated at 0 degree C with fixed SAC cells and injected i.p. into fresh tumour-bearing mice. If serum was given 7 days or less after B16 inoculation, the MST of the mice was highly significantly increased by up to 32%. Similar activity has been generated in normal human, rabbit and guinea-pig serum, while untreated sera were ineffective. Apparently the sera contained an inactive native precursor that was activated by the SAC to produce an anti-tumour agent. Precursor and product were both relatively labile at 0 degree C. Anti-tumour activity was eluted at pH 2.5 from SAC or Sepharose-protein-A pretreated with serum, thus implicating the protein A component of SAC. The eluates contained haemolytically active C1, the first component of complement, and five crude C1 preparations made by standard methods showed good anti-tumour activity. However, seven other highly haemolytic C1 preparations had no anti-tumour effect. Similarly, two crude preparations of the subcomponent C1q had good anti-tumour activity, but eight other, more pure and highly haemolytic C1q preparations were inactive in mice. Thus the anti-tumour principle was not C1 or C1q alone, although it had some chemical properties in common with these substances. It remains unidentified, but has potential interest for cancer therapy.

Animals↗
PubMed1982

Rapid induction of foci escaping density-dependent inhibition in baby mouse skin cultures.

Mesenchymal cells from primary BMS (baby mouse skin) cultures formed secondary monolayers subject to density-dependent inhibition. The monolayers remained quiescent but in good condition for 6-8 weeks if given weekly medium changes. Exposure of the primary cultures to fluorescent light and/or oxygen produced "altered" cells that gave rise in the secondary cultures to foci of up to 10(4) cells after 15 days. These foci overgrew the background BMS cells. The rate of growth, morphology, and arrangement of the altered cells varied greatly between foci but much less within a focus, which usually showed one or more characters of neoplastic cells. The initiation of foci was apparently not transmissible by an infectious agent.

Animals↗
PubMed1982

Enhancement of altered-cell foci in baby mouse skin cultures by antitubulin treatment: nuclear mechanisms.

When primary baby mouse skin (BMS) cultures were subcultured for 48 hours into media containing 10(-6) to 10(-7) M colchicine or demecolcine, the number of altered cell foci appearing after 3-4 weeks' maintenance at 36 degrees C was substantially enhanced over drug-free controls. This applied whether or not the primary cultures had been irradiated with white fluorescent light. The additional presence of cytochalasin D and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) sometimes improved and sometimes partly suppressed the enhancing effect of the antitubulin drugs, and these drugs were omitted for reproducible focus enhancement. The enhancement depended on passage through DNA synthesis in presence of colchicine, which did not prevent concurrent or subsequent DNA synthesis but induced a substantial proportion (greater than 33%) to replicate in the tetraploid (4n to 8n) chromosome configuration. Another effect was to induce widespread asymmetric nuclear division, allowing the potential for chromosome loss. All these effects occurred within the first one or few cell cycles after removal of the antitubulin drugs. The results suggest that the generation of tetraploidy perhaps followed by chromosome loss may be an important factor in the rapid induction of altered cell foci. Pre-existing DNA damage is another important factor.

Animals↗
PubMed1982

Properties of cell lines derived from altered-cell foci in baby mouse skin cultures.

Long-term cell lines were readily developed from a proportion of either baby mouse skin (BMS) cultures passing through colchicine-induced crisis or altered-cell foci selected from BMS cultures exposed to light and/or oxygen followed by colchicine. The developing cell lines behaved as though they passed through a continuing, profound genetic reshuffling process, which was usually lethal but which in some cases eventually yielded a gene set that favored long-term survival. Some cell lines have passed 120 cell doublings, and none has shown a second crisis or signs of senescence. As soon after isolation as measurement was possible (19-50 days) the cell lines were predominantly or entirely tetraploid or subtetraploid. Although BMS cells and all of the cell lines were density inhibited, the BMS, C14, C21 and C23 cells overgrew (formed colonies on) monolayers of the same cells in most combinations. The cell lines retained a variety of neoplastic morphological characters, although their morphology was more normal than in the original focus. No cell line, however, showed anchorage-independent growth or formed tumors in syngeneic hosts. The cell lines may all, therefore, be regarded as preneoplastic.

Animals↗
PubMed1980

Synthesis of virus DNA and polypeptides by temperature-sensitive mutants of rabbitpox virus.

Eighteen temperature-sensitive (ts) mutants of rabbitpox virus were examined for defects in synthesis of DNA and protein. Two mutants (ts-3 and ts-16) were defective in DNA synthesis (DNA-), since both incorporated significantly less than wild-type amounts of labelled thymidine into acid-precipitable material when infected cells were incubated at the restrictive temperature. Both these mutants gave only the 'early' class of virus polypeptides when infected cell extracts were examined by SDS--polyacrylamide slab gel electrophoresis following incubation at 40 degrees C. Nine of the remaining sixteen DNA+ ts mutants (ts-1, ts-2, ts-6, ts-12, ts-15, ts-17, ts-31, ts-32 and ts-33) synthesized wild-type levels of most virus polypeptides at 40 degrees C; six DNA+ ts mutants (ts-7, ts-8, ts-9, ts-11, ts-23 and ts-24) were defective in the post-translational cleavage of the polypeptides involved in membrane stabilization and particle assembly; one DNA+ ts mutant (ts-14) synthesized only the 'early' class of virus polypeptides, implying that either replicated DNA was not fully functional or that a specific early function was required for late transcription.

DNA, Viral↗
PubMed1980

Deletions of the terminal sequences in the genomes of the white pock (u) and host-restricted (p) mutants of rabbitpox virus.

The DNAs of wild-type rabbitpox virus (u+.p+), and selected u (white pock, u.p+) and p (white pock, PK-15 cell non-permissive, u.p) mutants were compared by restriction enzyme analysis. The cleavage fragments produced by digestion with HindIII or EcoRI endonucleases were separated by agarose gel electrophoresis. Deletions of approx. 10 x 10(6) were recognized at the right-hand terminus of each u mutant (three isolates), whereas deletions of 5 x 10(6) to 20 x 10(6) were detected at the left-hand terminus of each p mutant (nine isolates), Rapidly renaturing terminal restriction fragments, indicative of the covalent cross-links, were only found at the terminus unaffected by deleted sequences. Recombinant viruses that were wild-type in both genetic characters and in restriction pattern were recovered from mixed infections involving u and p mutants, but no genetic interaction was detected between crosses involving only u or p mutants. The p mutants were divided into two non-permissive classes dependent on their biochemical expression in PK-15 cells: the 'early' class which failed to replicate virus DNA and synthesized only the 'early' polypeptides and the 'late' class which appeared to be normal both in virus DNA and polypeptide synthesis. There was no correlation between the extent of the left-hand terminal deletion and the extent of permissiveness of the p mutants in PK-15 cells.

Animals↗