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Biomedical subjects

J Weston

Publications and source records attributed to J Weston.

50 records · Page 3Linked to original sources

Ipsiversive rotation in awake rats following chronic electrical stimulation of one caudate nucleus.

Rats were chronically implanted with stimulating electrodes in one caudate nucleus. Under light anaesthesia they received daily electrical stimulation (100-400 microA/HZ) for 30 min on 4 consecutive days. During this period, and for up to 3 subsequent days, tests for possible circling behaviour in response to administration of apomorphine i.p. were performed daily. Turning occurred towards the treated side and was reversible. The possibility is discussed that high levels of dopamine are released into the striatum during electrical stimulation, inducing transient subsensitivity of striatal dopamine receptors.

Animals↗

A non-cholinergic function for acetylcholinesterase in the substantia nigra: behavioural evidence.

Acetylcholinesterase is released from substantia nigra neurons, independently of cholinergic transmission. In an attempt to discover the functional significance of this phenomenon, the behavioural effects of injecting acetylcholinesterase into one substantia nigra of the rat were investigated. Following a single injection of the enzyme, intraperitoneal amphetamine evoked circling behaviour in a direction away from the side of injection. Purified acetylcholinesterase with a similar electrophoretic mobility to the endogenous secreted form, was far more potent in eliciting circling than much higher activities of commercial enzyme, consisting of several molecular species of acetylcholinesterase. Similar infusions of butyrylcholinesterase did not induce circling. Depending upon the amount of enzyme initially given, the behavioural effects of a single injection of acetylcholinesterase persisted for up to thirty days. During this period apomorphine, administered systemically, induced transient circling towards the acetylcholinesterase-treated side. It is concluded that secreted acetylcholinesterase has a functional significance within the substantia nigra, independent of cholinergic transmission. This released enzyme could exert long-term changes in the activity of the nigrostriatal system, involving modification of dopamine striatal receptors.

Acetylcholine↗

A re-examination of the incidence of circulating immune complexes in normal pregnancy.

Circulating immune complexes were detected in 20% of serum samples from pregnant patients by the liquid-phase C1q-binding assay. Two other immune complex assays yielded negative results with the same samples. A careful case study was also carried out in which serum samples from before, during and after a normal pregnancy were analysed. The results are discussed in relation to the contradictory data previously published in this field.

Antigen-Antibody Complex↗

Possible use of monoclonal antibodies to standardize the production and use of human urokinase.

Urokinase, a plasminogen activator found in urine is used in the treatment of pulmonary embolism, and is supplied commercially by several companies in Europe, U.S.A. and Japan. It exists in two forms, of molecular weights 50-55 000 and 33 000 daltons, which may differ in their therapeutic efficiency. A variety of assay systems exist to measure plasminogen activator activity--clot lysis, casein hydrolysis, amidolytic cleavage of synthetic peptide substrates. These assays are time-consuming, relatively insensitive, and cannot accurately assess the amount of the two molecular species in any preparation of urokinase. Standardization therefore presents a problem to manufacturers, control agencies, and clinicians. We have prepared a variety of monoclonal antibodies to human urokinase and have assessed their value as standardizing different commercial preparations of urokinase and measurement of urokinase for therapeutic monitoring.

Antibodies, Monoclonal↗

Purification and separation of tomato isolectins by chromatofocusing.

Tomato lectin can be rapidly separated from a crude extract of tomato fruit proteins by chromatofocusing. The lectin is recovered from a PBE94 column in two peaks, each with a specific activity comparable to that of lectin purified by affinity chromatography on ovomucoid-Sepharose. Both isolectins consist of a single polypeptide chain (Mr 68,000) and have similar properties.

Chromatography, Affinity↗

Immune abnormalities in diabetic patients not requiring insulin at diagnosis.

Islet cell antibodies (ICA), complement fixing islet cell antibodies, immune complexes and thyro-gastric autoantibodies were studied in newly diagnosed diabetic patients not requiring insulin at diagnosis. Particular attention was focussed on that minority of patients who are initially treated with diet or oral agents but show ICA in their serum. One hundred and six non-insulin-requiring patients were studied at clinical diagnosis. Seventeen who had ICA in their serum were compared with a control group of 89 who did not. The 17 ICA-positive diabetic patients were followed serologically for approximately 1 year from diagnosis. Patients were followed clinically for 3 years. Forty-seven percent of ICA-positive and 19% of ICA-negative patients had immune complexes in their serum. Eleven of the 17 ICA-positive patients also had serum complement fixing islet cell antibodies. Thyro-gastric antibodies were found in 29% of ICA-positive and 18% of ICA-negative diabetic patients. ICA, complement fixing antibody and immune complex positivity declined with time. Ten of the 7 ICA-positive and two of the 89 ICA-negative patients required insulin within 3 years of diagnosis. There was a positive trend for the presence of complement fixing islet cell antibodies at diagnosis to be associated with the early development of insulin dependency. The type of diabetes in ICA-positive patients not requiring insulin at diagnosis has strong immunological and clinical similarities to classical Type 1 (insulin-dependent) diabetes.

Antibodies↗

Humoral immunity in type 1 diabetes mellitus: a prospective study.

Cytoplasmic islet cell antibodies, as detected by anti-IgG (ICAb), and circulating immune complexes (AgAb), detected by the solid phase C1q test (C1qSP), were evaluated in 153 insulin dependent diabetics (IDD) at diagnosis and subsequently in 88 of these patients who were studied prospectively at regular intervals for up to 3 yr. AgAb detected by the conglutinin (KgBt) and Raji cell (RAJI) techniques were also studied at diagnosis in 34 and 50 diabetics respectively. Normal controls were included in the AgAb studies. Complement fixing islet cell antibodies (CF-ICAb) were evaluated in 30 randomly selected diabetics both at diagnosis and after 6 months. Viral antibodies (VAb) were measured in 30 IDD at diagnosis and in 30 matched controls. Insulin antibodies (IBC) were measured 9 months after diagnosis in 35 diabetics and HLA studies (B8 and B15) performed in 115 patients. In the prospective study the ICAb positivity declined from 50% at diagnosis to 45, 38, 36, 31, 26, 19 and 17% at 1, 3, 6, 9, 12, 24 and 36 months after diagnosis respectively. CF-ICAb were found in 30% of the diabetics at diagnosis and in 23% at 6 months. All patients with CF-ICAb at diagnosis were ICAb positive whilst only 47% of patients with ICAb also had CF-ICAb in the serum. AgAb were found at diagnosis in 35% of patients by C1qSP (p less than 0.001 vs. normals), in 35% by KgBt (p less than 0.001) and in 54% by RAJI (p less than 0.002). Eighty-four patients were studied at diagnosis by more than one AgAb method and of these 57% had at least one positive AgAb result. AgAb by C1qSP declined to less than 20% within 6 months of diagnosis. AgAb, as measured by C1qSP and RAJI techniques, correlated with ICAb at diagnosis whereas there was no correlation with VAb levels, IBC values, nor with the HLA antigens. There was no correlation between AgAb (C1q) and CF-ICAb. HLA B15 positive patients tended to form higher IBC levels than B15 negative patients. Thus, AgAb presence seems to parallel that of ICAb in the early stages of diabetes and both phenomena may be primarily or secondarily involved in the development of the disease.

Adult↗

Some studies on the polyethylene glycol turbidity method for detecting immune complexes in serum.

A rapid and simple method for detecting circulating immune complexes based on turbidity measurements following polyethylene glycol precipitation was studied with regard to its suitability as a routine assay in clinical laboratories. This method was found to have an acceptable degree of precision provided the temperature was carefully controlled. The mean value obtained with a group for 70 blood donors was 0.09 (SD 0.05) and the 90th percentile value was 0.16. There was no significant difference between values obtained from groups divided on the basis of age or sex. Of 70 diabetic sera assayed by the polyethylene glycol turbidity method, 20% gave positive values although only 10% were strongly positive. The corresponding figures for the solid phase Clq binding method were 15.7% and 14.3%, respectively. Correlation between the two methods was poor. It was concluded that although both methods have a similar likelihood of detecting immune complexes in randomly selected diabetics, it is probable that different immune complexes were being detected.

Antigen-Antibody Complex↗

Intensive plasma exchange in rhesus isoimmunisation.

Intensive plasma exchanges were carried out in a 34-year-old pregnant woman to lower the level of circulating anti-D. The patient proved interesting from a number of serological aspects. The possible protective effect of coexistent ABO incompatibility is discussed. The effect of plasma exchanges on cytotoxic HLA antibodies is also demonstrated.

Adult↗

Application of acetylcholinesterase to the substantia nigra induces stereotypy in rats.

In the substantia nigra, acetylcholinesterase may have a non-cholinergic function. Previous work suggests that release of acetylcholinesterase locally in the substantia nigra leads to a net increase in dopaminergic activity in the ipsilateral striatum. To investigate this hypothesis, acetylcholinesterase was microinjected bilaterally into the substantiae nigrae of awake rats and stereotyped behaviour used as an indication of increased dopaminergic activity in the striatum. Acetylcholinesterase increased stereotypy in rats, while butyrylcholinesterase and the vehicle, distilled water, were ineffective. The functional significance of acetylcholinesterase in the substantiae nigrae of freely moving animals is discussed in the light of its apparent association with dopaminergic rather than cholinergic systems.

Acetylcholinesterase↗