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Biomedical subjects

W C Davis

Publications and source records attributed to W C Davis.

At least 235 records · Page 13Linked to original sources
PubMed1982

Immunoselection of tumor variants resistant to antibody-mediated cytotoxicity. Their immunologic and metastatic characterization.

The immunological characteristics of two series of metastatic variants of restricted genetic origin were related to their lung-colony-forming potential. A series of metastatic variants was isolated from a tumor-cell population in which heterogeneity appeared following short-term in vivo passage, while a second series of variants were immunoselected in vitro for resistance to antibody-complement-mediated cell lysis. In the case of the first series, the sensitivity of the individual variants to cell-mediated and antibody-complement-mediated cytotoxicity appeared to be partly determined by the number and rate of loss of antibody-binding sites on the cell surface. These characteristics also correlated with the efficiency of experimental metastasis in the animal. We compared the results reported herein with our previous studies of nonimmune parameters for this series of metastatic variants, and we conclude that immunological differences can be important to the efficiency of lung-colony formation. However, in the case of the second series of variants, despite selection in vitro for resistance to antibody-complement-mediated cell lysis, the behavior of these variants in the lung colony assay could not be predicted by the immunologic parameters examined.

Animals↗
PubMed1982

Detection of early pregnancy factor in swine: A need for dialogue.

The rosette inhibition test, which has been used to detect early pregnancy factor (EPF) and other immunosuppressive factors in the serum of pregnant mice, women, and sheep, was adapted for use in swine. Since the initial methods described for use of the assay were cumbersome and time consuming, our first efforts were to simplify the technique. Substitution of microtiter plates for test tubes and treatment of sheep erythrocytes with AET to increase numbers and stability of the rosettes were successful. Although consistently higher rosette inhibition titers were obtained after incubation of lymphocytes in the serum of pregnant sows compared to controls, the variability in numbers of rosettes obtained on a day to day basis and the cumbersome nature of the test have impeded progress in firmly establishing the presence of EPF in pregnant swine and demonstrating the homology between it and the EPF reported in other species.

Journal Article↗
PubMed1982

Molecular interactions of etazolate with benzodiazepine and picrotoxinin binding sites.

Pyrazolopyridines, such as etazolate (SQ 20009), enhance [3H]diazepam binding to a Lubrol-solubilized fraction that has specific binding sites for 3H benzodiazepines, [alpha-3H]dihydropicrotoxinin (DHP) and [3H]muscimol. Etazolate enhancement of [3H]diazepam binding was inhibited by picrotoxinin. Furthermore, etazolate inhibited the [3H]DHP binding in a Lubrol-solubilized fraction with an IC50 value of 6-8 microM. These results provide evidence that etazolate, like pentobarbital, modulates benzodiazepine binding via the DHP-sensitive site of the benzodiazepine-GABA receptor-ionophore complex.

Animals↗
PubMed1982

Dwarfism in Alaskan malamutes: a disease resembling metaphyseal dysplasia in human beings.

In a study of 300 Alaskan Malamutes, dwarfism was shown to be an autosomal recessive inherited disease with complete penetrance that resulted in disturbed endochondral bone formation. Osseous growth disturbance was manifest at the metaphyses of tubular bones. Clinical and radiographic changes were very similar to those of rickets, although appositional bone formation rates were normal. Serum calcium, phosphorus, and alkaline phosphatase were within normal limits. Urinary excretion of calcium, phosphate, and amino acids were normal. Excess matrix was formed in the zone of cartilage cell proliferation, and the matrix persisted in the growth plate. Normal stresses resulted in microfractures in the metaphyses with subsequent interference of vascular penetration into the zone of degenerated cartilage cells.

Alkaline Phosphatase↗
PubMed1982

Isolation of a retrovirus from cultured equine sarcoid tumor cells.

A virus with the morphologic and biochemical properties of the family Retroviridae has been isolated from cultured cells explanted from a malignant tumor induced by intradermal inoculation of equine sarcoid cells into a combined immunodeficient Arabian foal. By electron microscopy, intracytoplasmic, extracellular, and budding particles measuring 89 to 120 nm with electron-lucent cores were seen. Virus purified from the medium of cultured cells had a buoyant density of 1.15 g/cm3 in isopycnic sucrose-gradient centrifugation, incorporated radiolabeled uridine but not thymidine, and had constitutive RNA-dependent DNA polymerase which required Mn2+ for optimal endogenous activity.

Animals↗
PubMed1981

Pentobarbital enhances [3H]diazepam binding to soluble receptors at the benzodiazepine--GABA-receptor-ionophore complex.

Pentobarbital enhances [3H]diazepam binding to soluble receptors in a dose-dependent and saturable manner. Half-maximal enhancement occurred at 110 micrometers pentobarbital. This enhancement was due to an increase in the affinity of diazepam to its receptor sites. Pentobarbital enhancement was blocked by picrotoxinin and bicuculline. These results are similar to those reported for membranes and suggest that various components of the benzodiazepine--GABA-receptor-ionophore complex are intimately associated.

Animals↗
PubMed1981

Solubilization of the picrotoxinin binding receptor from mammalian brain.

The binding sites for alpha-dihydropicrotoxinin (DHP), which is a ligand for the picrotoxin-sensitive component at the benzodiazepine-gamma-aminobutyric acid-receptor-ionophore complex, has been solubilized from rat brain, using 1% Lubrol. A new assay, which involves precipitation of the [3H]DHP-soluble protein complex by gamma-globulin and polyethylene glycol (PEG), followed by centrifugation, is described. The solubilized material bound DHP to two sites with apparent affinities of 0.038 and 1.85 microM. The binding of DHP to the solubilized receptors was inhibited by convulsant and depressant drugs with potencies similar to those required for membrane receptors. The ability of barbiturates to inhibit DHP binding to both solubilized and membrane receptors strongly suggests that barbiturates may interact with the picrotoxin binding component. These data suggest that ligand recognition properties of the picrotoxinin binding are not altered by solubilization. The binding was abolished by urea and partially destroyed by heating the soluble extract at 65 degrees C for 30 min. This new method of measuring the binding of ligands to the solubilized receptors by PEG centrifugation might be used successfully in other solubilization studies.

Animals↗
PubMed1981

Picrotoxinin and diazepam bind to two distinct proteins: further evidence that pentobarbital may act at the picrotoxinin site.

alpha-[3H]Dihydropicrotoxinin (DHP) and [3H]diazepam binding proteins were solubilized from rat brain membranes with 1% Lubrol-Px. Gel filtration of the Lubrol-solubilized fraction revealed that [3H]DHP and [3H]diazepam bind to two distinct peaks with apparent molecular weights of 185,000 and 61,000, respectively. The signal-to-noise ratio of [3H]DHP binding to 185,000-dalton fractions was improved significantly. [3H]DHP bound to the 185,000-dalton fraction with two binding constants. Muscimol and pentobarbital, while enhancing [3H]diazepam binding to membrane and crude Lubrol-solubilized fractions, failed to enhance [3H]diazepam binding to the 61,000-dalton fraction. Pentobarbital inhibited the binding of [3H]DHP to the 185,000-dalton fraction with an IC50 value of 60 +/- 12 micro M. The binding of [3H]DHP alos was inhibited by several depressant and convulsant drugs which affect gamma-aminobutyric acid (GABA)-mediated transmission. These results provide strong evidence that picrotoxinin and diazepam bind to two distinct proteins and that pentobarbital may act at the picrotoxinin-sensitive site of the benzodiazepine . GABA receptor . ionophore complex.

Animals↗
PubMed1979

Introduction of metastatic heterogeneity by short-term in vivo passage of a cloned transformed cell line.

An experimental system for the study of metastasis has been developed using an epithelioid cell line of hepatic origin which had previously been chemically transformed in vitro. These metastatic cells were studied in the syngeneic rat strain. The cloned parent cell line metastasizes only to the lungs following intravenous, subcutaneous, or intraperitoneal injection. The metastatic phenotype is stable during in vitro passage, and subclones from the parent clone have a metastatic capacity statistically similar to that of the parent clone. Following ascites passage of the parent cell line, the cell population obtained exhibits the same metastatic ability as the parent clone. However, subclones obtained from the ascites-passaged population exhibit metastatic heterogeneity. This heterogeneity is introduced by the host passage and not by in vitro culture or subcloning. In the case of the two metastatic variants examined, the difference in the metastatic phenotype is found not to be due to differences in arrest or trapping of the cells but appears to be related to long-term survival and proliferation of the tumor cells following their arrest in the lungs. Morphologically the variants are very similar, and growth of the metastatic foci provokes a vigorous inflammatory response by the host.

Animals↗
PubMed1979

Enhancement of heart allograft survival across H-2D differences.

The use of split heart allografts in the study of immunological enhancement was evaluated. The study revealed that, in contrast to the results with skin grafts, it is possible to obtain exceptional increases in the survival of heart grafts across differences at the H-2D end of the H-2 complex. The factors affecting graft survival were the age of the heart tissue used in grafting, the haplotype of the donor and host, the regimen of injections of antibody, and the immune reagent used. The data suggest that a difference exists in the mechanism by which anti-Ia and anti-H-2D antibodies mediate their enhancing effect.

Animals↗
PubMed1979

Canine granulocytopathy syndrome: an inherited disorder of leukocyte function.

A disease closely resembling the human neutrophil dysfunction syndromes has been identified in a colony of dogs. The syndrome, referred to as the canine granulocytopathy syndrome, is characterized by recurrent-life-threatening bacterial infections and a greatly shortened life span. The disease is genetically determined, being transmitted as an autosomal recessive trait. The increased susceptibity to pyogenic infections and shortened life span is related to an impairment of leukocyte function at the cellular level. Preparation of neutrophils from affected animals exhibit impaired in vitro killing of Esherichia coli. The defect in bactericidal activity is associated with reduced glucose oxidation by the hexose monophosphate shunt and an increase capacity to reduce nitroblue tetrazolium dye. The data obtained thus far indicate the canine granulocytopathy syndrome will be of considerable value as a model for study of granulocytypathy sydromes in man.

Animals↗