Search PubMed⌕ Search

Biomedical subjects

C MacDonald

Publications and source records attributed to C MacDonald.

At least 91 records · Page 5Linked to original sources
PubMed1988

Immunogenicity of liposome-bound hyaluronate in mice. At least two different antigenic sites on hyaluronate are identified by mouse monoclonal antibodies.

Hyaluronate (HA) was previously demonstrated to be immunogenic in rabbits. The immunogenicity of HA in mice was studied. Hyaluronidase-digested streptococcal HA (IA1) covalently linked to liposomes (IA1-liposomes) were produced for immunization. Mice immunized with IA1-liposomes developed measurable serum antibodies to IA1, while mice immunized with IA1 in Freund's adjuvant did not. mAbs produced by two stable hybridomas (10G6 and 5F11) from mice immunized with IA1-liposomes produced IgG antibody reactive with HA in ELISA. 10G6 had a much higher avidity for liposome-bound IA1 than free IA1, while 5F11 did not, suggesting that the mode of presentation of IA1 is important in HA immunogenicity and antigenicity. Both mAbs recognized terminal HA immunodeterminants exposed by hyaluronidase treatment. Sonication had no effect on HA reactivity for either mAb. However, ascorbic acid treatment significantly reduced the antigenicity of HA for mAb 5F11, but not 10G6. Only 10G6 was inhibited by glucuronic acid. Electrostatic forces appear to play a role in the binding site of 5F11, but not 10G6. 5F11 crossreacts with heparan sulfate and phosphorylcholine, while 10G6 did not crossreact with any glycosaminoglycans or phosphorylated compounds tested. These results confirm that HA is immunogenic. They suggest that the mode of presentation of HA is important for the induction of the immune response, and in HA antigenicity. At least two different antigenic sites on HA were demonstrated. 10G6 recognizes a terminal HA antigenic site expressed on IA1-liposomes that contains glucuronic acid in its immunodominant site. 5F11 recognizes an HA antigenic site in which electrostatic forces appear to play a role, is sensitive to ascorbic acid treatment, and is crossreactive with heparan sulfate. The use of mAbs should facilitate immunologic studies of HA.

Animals↗
PubMed1988

Thyroid function and bipolar affective disorder.

Thyroid function tests and life course of illness were evaluated in 42 patients with bipolar affective disorder who had received at least 3 months of lithium carbonate treatment. Eight of 42 patients (19%) required thyroid replacement or had evidence of subclinical hypothyroidism associated with lithium treatment. Abnormalities of thyroid function were related to female sex and duration of lithium treatment but not to a rapid-cycling course of illness.

Adolescent↗
PubMed1988

Experimental infection of Phlebotomus papatasi with sand fly fever Sicilian virus.

Experimental studies were conducted to evaluate humans as hosts infecting the sand fly Phlebotomus papatasi with sand fly fever Sicilian (SFS) virus. Viral antigen and infectious virus circulated in the blood of infected volunteers on days 4 and 5 after intravenous inoculation with SFS virus. Viremia levels during the latter period were high enough to infect feeding sand flies, but only 13% (9/69) of the flies became infected. One out of every 3 infected sand flies that survived to feed a second time transmitted SFS to a hamster. These results confirm a vertebrate-sand fly-vertebrate transmission cycle for SFS virus, and demonstrate that horizontal transmission may contribute to the maintenance of this virus in nature.

Animals↗
PubMed1988

Lack of differential cognitive effects of lithium and carbamazepine in bipolar affective disorder.

Cognitive functioning was assessed in medication-free as well as carbamazepine- and lithium-treated patients with manic-depressive illness. Across a range of tests measuring attention, concentration, visuomotor function, and memory, no significant differences were observed across the three patient groups as compared with control subjects without manic-depressive illness. The clinical and theoretical implications of these findings are discussed.

Adult↗
PubMed1986

Maintenance of expression of differentiated function of kidney cells following transformation by SV40 early region DNA.

This study describes the isolation and characterization of epithelial cell lines that maintain their differentiated phenotype following the stable integration of SV40 genes. Epithelial cells were derived from a defined location of rabbit kidney, the thick ascending limb of Henle's loop, and were co-transfected with genes from the early region of SV40 together with pSV2-neo DNA (which confers resistance to the antibiotic G418). These cells were shown to be resistant to G418, express SV40 large T-antigen and continued to express differentiated characteristics typical of cells of their origin. Such characteristics include the expression of high levels of activity of both Na,K-ATPase and the functionally important Na,K,Cl-co-transport system, the synthesis of Tamm-Horsfall glycoprotein and the presence of a barium-sensitive K+ channel on the apical membrane surface.

Animals↗
PubMed1986

The effects of some atypical neuroleptics on apomorphine-induced behaviors as a measure of their relative potencies in blocking presynaptic versus postsynaptic dopamine receptors.

The effects of the atypical neuroleptics clozapine, thioridazine and sulpiride on behaviors induced by apomorphine were recorded, using a time-sampling observational paradigm. A low dose of apomorphine (0.1 mg/kg, SC) produced hypomotility. Of the neuroleptics tested, only sulpiride antagonized this hypomotility. Apomorphine in higher doses (0.2-1.0 mg/kg, SC) produced stereotyped behaviors (sniffing down and licking or gnawing). All three atypical neuroleptics antagonized stereotypy. The effects of sulpiride on apomorphine-induced hypomotility and stereotypy are consistent with the notion that this drug has strong presynaptic and weak postsynaptic blocking effects at dopamine receptors. The mechanisms of action of clozapine and thioridazine may be different from that of sulpiride. Perhaps the anticholinergic activities of these drugs mediate some of their behavioral effects. The effects of these atypical neuroleptics on apomorphine-induced stereotypy are opposite in direction to their effects on amphetamine-induced stereotypy, suggesting that these two behavioral patterns are not measures of the same neural process.

Amphetamine↗
PubMed1986

Evidence that thioridazine enhances amphetamine-induced stereotypy via anticholinergic activity.

The hypothesis that the anticholinergic properties of thioridazine can account for its ability to enhance amphetamine-induced stereotyped behaviors was tested. In one experiment, scopolamine-induced repetitive head movements were shown to be potentiated by thioridazine. In another experiment, subthreshold doses of scopolamine and thioridazine interacted to potentiate amphetamine-induced repetitive head movements. The data suggest that thioridazine, in addition to its neuroleptic activity, has significant anticholinergic effects in vivo and these effects may account for its potentiation of amphetamine-induced stereotypy.

Animals↗
PubMed1985

Opposite effects of sulpiride and metoclopramide on amphetamine-induced stereotypy.

The effects of the atypical neuroleptic sulpiride (0-20 mg/kg s.c.) and the classical neuroleptic metoclopramide (0-4 mg/kg s.c.) on behaviours produced by D-amphetamine (0-5 mg/kg i.p.) were measured in a time-sampling observational paradigm in rats. Sulpiride had one clear dose-dependent effect: it enhanced amphetamine-induced stereotyped behaviours (repetitive head movements, sniffing down and some gnawing). In contrast, metoclopramide dose-dependently decreased amphetamine-induced stereotypy, locomotion, rearing, and sniffing up, and concurrently antagonized the suppression of lying down produced by amphetamine. Sulpiride's facilitatory effects on amphetamine-induced stereotypy follow a pattern previously observed for two other atypical neuroleptics: clozapine and thioridazine. This may be a common effect of atypical neuroleptics. Since these neuroleptics are antipsychotic, amphetamine-induced stereotypy appears to be a poor animal model for human psychoses. It is suggested that sulpiride's effects may be mediated through a preferential presynaptic versus postsynaptic action on dopamine neurons in the nigrostriatal bundle.

Amphetamine↗
PubMed1985

Pathologic features of the CHARGE association: support for involvement of the neural crest.

Defects associated with choanal atresia include coloboma, cardiac anomalies (usually involving the conotruncal region), physical or mental retardation, genital hypoplasia, and abnormalities of the ear. This constellation of defects is known as the "CHARGE" association and may be accompanied by other anomalies. Many of these defects seem to result from abnormalities in the development, migration, or interaction of cells of the cephalic neural crest. The range of variation in neural crest development is substantial, as indicated by the rather large number of malformation complexes and syndromes that are related phenotypically to the CHARGE association. The increasingly unwieldy nature of this collection of malformations demonstrates the need for an expanded classification of the "neurocrestopathies."

Abnormalities, Multiple↗
PubMed1985

The immortalization of human lymphocytes by spheroplast fusion.

A method for immortalizing animal cells based on the spheroplast fusion technique of Schaffner is being developed. Human lymphocytes have been fused with E. coli spheroplasts containing the plasmid pTSV3, which represents the entire SV40 genome cloned into the EcoRI restriction enzyme site of the plasmid pAT153. The efficiency of transformation was examined using pTSV3 and derivatives which have deletions in parts of the late gene sequences. Although there was a marked increase in the survival time of the lymphocyte cultures after fusion compared with cells which had been mitogen-stimulated but not fused, the cells did not continue to proliferate indefinitely. Attempts are now being made to extend the survival time by culturing the transformed lymphocytes in the presence of feeder cells.

Cell Division↗
PubMed1984

Atypical neuroleptics clozapine and thioridazine enhance amphetamine-induced stereotypy.

The effects of the atypical neuroleptics clozapine and thioridazine and the typical neuroleptic pimozide on amphetamine-induced behavior were examined. Pimozide, as expected, blocked both amphetamine-induced locomotion and stereotypy. Thioridazine and clozapine antagonized the increases in locomotion produced by amphetamine, but produced increases in amphetamine-induced stereotypy and lowered the threshold dose for stereotypy. It is suggested that the increased stereotypy might partly account for the decreased locomotion, and that this might be a primary effect of these atypical neuroleptics. The data would also suggest that the use of amphetamine-induced stereotypy as a model for psychosis is inappropriate, as clozapine and thioridazine, which enhance stereotypy, are antipsychotic.

Animals↗
PubMed1983

Apparent species restriction in the isolation of proliferating embryonal carcinoma cell hybrids.

Proliferating somatic cell hybrids are readily obtained from the fusion of a metabolic co-operation-defective mouse embryonal carcinoma cell variant (R5/3) to LMTK- (1 fibroblastic mouse line derived from L-M) and to derivatives of the R5/3 parental cell line PC13. However it has not yet proved possible to produce growing hybrids from fusions between R5/3 and any non-mouse cell line. It appears, from both this work and that of others that although polyethylene glycol-induced fusion occurs between embryonal carcinoma cells and other cell types viable hybrids cannot always be isolated.

Animals↗