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Biomedical subjects

C Dobson

Publications and source records attributed to C Dobson.

At least 37 records · Page 2Linked to original sources
PubMed1993

Babesia bovis: in vitro phagocytosis promoted by immune serum and by antibodies produced against protective antigens.

The in vitro phagocytosis of both Babesia bovis-infected red cells and of parasites exposed by lysis of infected red blood cells is demonstrated in a phagocytic mouse model. Twenty-four B. bovis immune sera were tested alone or as a pool as were antibodies (DS antibodies) raised against a B. bovis protective fraction, prepared by dextran sulfate precipitation. All the immune sera failed to promote significant levels of phagocytosis, whereas the other antibodies (DS antibodies) consistently induced phagocytosis of infected cells in all the experiments carried out. This study shows that antibody specificity is critical to the opsonization of infected red cells and parasites during in vitro phagocytosis and suggests that phagocytosis is one of the mechanisms in the in vivo immune response against Babesia species.

Animals↗
PubMed1991

The effect of immune serum and complement on the in vitro phagocytosis of Babesia rodhaini.

The effect of immune serum and complement on the in vitro phagocytosis of Babesia rodhaini was investigated. Infected erythrocytes and parasites released from erythrocytes by lysis were phagocytosed by mouse peritoneal macrophages in vitro when the infected erythrocytes or parasites were exposed to hyperimmune B. rodhaini serum. Complement, in the presence of immune serum, did not reproducibly enhance phagocytosis of infected erythrocytes or parasites alone. When adjusted for its effect on normal erythrocytes and normal serum, complement generally inhibited rather than enhanced phagocytosis. When coupled with other published data, our data suggest that the activation of the immune system in vivo against this species of Babesia involves a series of mechanisms of which phagocytosis is but one.

Animals↗
PubMed1991

Evaluation of HP 029 (velnacrine maleate) in Alzheimer's disease.

HP 029 (1,2,3,4-tetrahydro-9-aminoacridin-1-ol-maleate) is a cholinesterase inhibitor and one of a series of compounds synthesized at Hoechst-Roussel Pharmaceuticals Inc. (HRPI) as a potential therapeutic agent for senile dementia of the Alzheimer type (SDAT). An ongoing clinical development program for HP 029 (velnacrine maleate) reflects a rational, traditional progression from therapeutic concept through clinical evaluation. Prior to the initiation of outpatient studies, sufficient data had been obtained from normal volunteers and hospitalized patients to support the following conclusions: the pharmacokinetic profile of HP 029 in young and elderly normal men is predictable; tolerance and safety data for HP 029 using normal volunteers poorly correlates with experience in patients with SDAT; patients with SDAT exhibit marked intersubject variability in tolerance within a suspected therapeutic dose range; mandatory endpoints for drug discontinuation for outpatients can be reliably established in an inpatient environment. Subsequently, Protocol 201 was initiated as a multicenter, multistage investigation of HP 029 in patients with probable SDAT (NINCDS-ADRDA criteria). A dose-ranging component determined patient eligibility for a subsequent dose-replication phase based upon explicit safety and efficacy criteria defined within protocol. One a priori specified interim analysis was conducted by the sponsor (HRPI) for administrative purposes after completing approximately 50% of the planned sample (September 1989). Results suggested that (1) beneficial effects of HP 029 existed on key and secondary measures for the approximately 30% of enrolled patients; (2) interim results would provide an accurate reflection of the results at the conclusion of the study (1991); (3) HP 029-induced hepatocellular injury appeared to be a reversible, predominantly dose-related event; and (4) cholinergically mediated adverse events are infrequent and clinically inconsequential at dosages less than or equal to 225 mg/day. Post hoc hypotheses based on the interim dataset suggest that: (1) carry-over effects of HP 029 exist within a dose-ranging/dose-replication paradigm that militate against the utility of an "enriched population" design; (2) beneficial effects are more robust on initial exposure to HP 029 with effects discerned on both memory and arousal; (3) patient characteristics associated with toxicity or response are not identified; (4) dosage reduction in subsequent efficacy trials may reduce hepatocellular injury and yield clinically unimportant differences in overall efficacy results.

Aged↗
PubMed1991

Potential clinical use of an adrenergic/cholinergic agent (HP 128) in the treatment of Alzheimer's disease.

A novel compound designated HP 128, which manifests adrenergic and cholinergic properties, was administered for 10 days to patients with Alzheimer's disease in a double-blind, placebo-controlled trial. All patients who entered the trial had previously failed to respond to a structurally related cholinesterase inhibitor without adrenergic properties (HP 029). The primary purpose of the study was to assess the safety and tolerance of HP 128. Efficacy measures were obtained to generate hypotheses for possible future studies. In the dosage range examined, HP 128 was safe and well tolerated. Effects on clinical measures of dementia severity were equivocal.

Aged↗
PubMed1991

Genetic variation and host-parasite relations: Nematospiroides dubius in mice.

Our work deals with aspects of the genetics and immunology of host-parasite relationships as they influence the development of protective immunity and the phenomenon of coevolution. The aim is to understand parasitism through analyses of host specificity. In earlier studies we examined the inheritance of resistances in mice to infections with Nematospiroides dubius (=Heligmosomoides polygyrus) and established the predominant role played by antibodies in protective immunity. Here we report information concerning the selection of lines of N. dubius that differ in their ability to survive antagonistic immunological reactions from mice. Challenge infections with groups of these mice, immunized and protected by previous repeated infections, show that worms selected to survive the immunity that kills other worms do so by inhibiting the effectiveness of the cellular rather than humoral elements of protective immunity.

Animals↗
PubMed1990

In vitro adherence of erythrocytes infected with Babesia bigemina and Babesia rodhaini to thrombospondin.

The adherence of erythrocytes infected with Babesia bigemina and Babesia rodhaini to thrombospondin (TSP) in vitro is demonstrated. Blood with a range of parasitaemias was used and counts of cells which bound to TSP on plastic were significantly different from the controls with both Babesia species. These studies indicated that TSP receptors are present on the surface of red blood cells infected with the two Babesia species, although these parasites do not alter the membranes of infected erythrocytes obviously and do not cause cerebral symptoms in their hosts. Erythrocytes infected with either B. bigemina or B. rodhaini do not adhere to other erythrocytes in vivo, probably because these parasites induce mild infections in their hosts, but they can adhere to TSP in vitro.

Animals↗
PubMed1989

Nematospiroides dubius: influence of adjuvants on immunity in mice vaccinated with antigens isolated by affinity chromatography from adult worms.

Five adjuvants were examined for their ability to potentiate the immune response of mice to soluble antigens from adult Nematospiroides dubius prepared by affinity chromatography against antibodies from repeatedly infected mice as ligands (IMIgAg). Immunized mice were better protected against N. dubius by IMIgAg injected intraperitoneally with either pertussigen (75%) or aluminium hydroxide (Alum) (67%) as adjuvants than with Freud's complete (54%) or incomplete adjuvants (31%). Protection was correlated with elevated specific antibody values and with cellular responses. Quil A was toxic to recipient mice at the concentration used. Alum may be a more practical adjuvant than pertussigen, which may activate protective immunity only in specific recipient genotypes and oil-based adjuvants which appear to be less efficient, to vaccinate mice with soluble parasite antigens.

Adjuvants, Immunologic↗
PubMed1989

Immunity in mice vaccinated with a molecular weight 60,000 glycoprotein secreted by adult Nematospiroides dubius.

A mol. wt 60,000 glycoprotein was purified from adult Nematospiroides dubius excretory-secretory products (ES) by polyacrylamide gel electrophoresis and electroelution and used to vaccinate BCF1 mice. This molecule is also released from the surface of the parasite and can be cleaved by pepsin. Mice immunized twice with ES 60,000 in Alum adjuvant harboured similar numbers of N. dubius as did control mice but voided 40% fewer parasite eggs in their faeces. The mol. wt 60,000 component in ES and from the surface of the parasite appears to influence how the parasite reproduces and may be important to its survival.

Animals↗
PubMed1989

Low molecular weight immunosuppressors secreted by adult Nematospiroides dubius.

Adult Nematospiroides dubius excretory-secretory products (ES) were collected from worms cultured in vitro, separated by sodium dodecyl sulphate--polyacrylamide gel electrophoresis (SDS-PAGE) into four fractions (FI-IV), electroeluted and assessed for their ability to inhibit the proliferation of mouse lymphocytes stimulated by mitogens in vitro. The proliferation of mitogen- and ES-stimulated mouse spleen lymphocytes from normal and infected mice was inhibited by low mol. wt ES F-IV (less than 26,000).

Animals↗
PubMed1989

Proteolytic enzymes in excretory-secretory products from adult Nematospiroides dubius.

Excretory-secretory products (ES), collected from in vitro cultures of adult Nematospiroides dubius, were examined for proteolytic enzyme activity. ES enzymes had a pH optimum of 8.0 and their activity was sensitive to serine-proteinase inhibitors. Three SDS-resistant proteases were identified in ES at molecular weight (mol. wt) 200,000, 105,000 and 48,000 by incorporating substrates into the matrices of sodium dodecyl sulfate-polyacrylamide electrophoresis (SDS-PAGE) gels.

Animals↗
PubMed1989

In vitro adherence of bovine erythrocytes infected with Babesia bovis to thrombospondin and laminin.

This study was undertaken to examine how eight putative adhesive agents bound to plastic surfaces affected the capacity of bovine erythrocytes, infected with either virulent or avirulent strains of Babesia bovis, to adhere in vitro. Thrombospondin (TSP) induced B. bovis-infected bovine erythrocytes to adhere and adherence was augmented when the infected blood was cultured for 24 h before the assay. Moreover, TSP also caused erythrocytes infected with avirulent strains of B. bovis to adhere to plastic in vitro. Laminin promoted the adherence of infected, and to a lesser extent, of uninfected erythrocytes.

Animals↗
PubMed1989

Excretory-secretory antigens from adult Nematospiroides dubius.

Adult Nematospiroides dubius excretory-secretory (ES) products were collected from worms cultured in vitro, radiolabelled and separated by sodium dodecyl polyacrylamide gel electrophoresis (SDS-PAGE). The components were characterized and assessed for molecular weight (MW) after autoradiography and gel staining, for antigenicity in immunoblots, for sensitivity to protease enzymes, and for carbohydrate content. ES contained at least 18 denatured components from MW less than 20,000 to greater than 200,000. At least one of the surface proteins of adults was found with the ES antigens recovered when adults were cultured in vitro. Molecules with MW 200,000, 78,000 and 60,000 were glycoproteins and reacted with immune mouse serum in Western blots. The dominant ES, MW 60,000 component stained with periodic acid-Schiff (PAS), bound lectins with affinity for D-mannose, and was resistant to peptic and tryptic but not V8 protease digestion.

Animals↗
PubMed1989

Hereford cattle protected against Boophilus microplus with antigens purified by immunoaffinity chromatography from larval and adult ticks.

Tick larvae (Boophilus microplus) were extracted, fractionated by gel filtration and ion-exchange chromatography, and the fractions assayed by enzyme-linked immunosorbent assay (ELISA) against sera from cattle immunized and protected by antigens from the mid-gut of adult ticks. Unfractionated, whole larval extracts and selected reactive components were used to vaccinate cattle; they decreased the number of ticks dropped after challenge, but the effect of treatment was not significant. Antigens purified from crude larval extracts by affinity chromatography, using immunoglobulin ligands from an immune steer vaccinated with tick mid-gut antigens, also failed to protect cattle. However, tick extracts from both larval and adult ticks, which were first separated into membrane-associated and soluble fractions and then purified by exposure to the affinity ligands, protected cattle greater than 80% against subsequent challenge with ticks.

Animals↗
PubMed1988

Hereford cattle immunized and protected against Boophilus microplus with soluble and membrane-associated antigens from the midgut of ticks.

Hereford cattle were immunized with membranes and soluble components extracted from the midgut of Boophilus microplus. Membrane vaccines protected cattle (91%) against challenge with 3 x 20,000 larval ticks administered at intervals of 7 days. Vaccines made from soluble antigens did not protect cattle. Antibody levels measured by enzyme-linked immunosorbent assay (ELISA) related to the levels of protection induced by vaccination.

Animals↗