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Biomedical subjects

G L Watkins

Publications and source records attributed to G L Watkins.

At least 55 records · Page 3Linked to original sources
PubMed1989

PET imaging of human gliomas with ligands for the peripheral benzodiazepine binding site.

Human gliomas were imaged in vivo using ligands for the peripheral-type benzodiazepine binding site (or omega 3 binding site) and positron emission tomography (PET). Although gliomas have a high density of the peripheral-type benzodiazepine binding site, PET scans with a selective ligand for this site, [11C] Ro5-4864, failed to demonstrate higher radioactivity levels in human gliomas than in brain. In vitro studies of surgically removed specimens of human glioma demonstrated little binding of Ro5-4864 but high levels of binding of another selective ligand, PK 11195. Scans with [11C]PK 11195 demonstrated increased radioactivity in glioma compared to brain in 8 of 10 patients. Radioactivity in tumor and the ratios of radioactivity in tumor to that in remote gray and in white matter correlated significantly with the specific activity of [11C]PK 11195, suggesting that accumulation represents saturable high-affinity binding. We conclude that the PK 11195 manifests greater binding than Ro5-4864 to the peripheral-type benzodiazepine binding site on human gliomas and that human gliomas can be successfully imaged using [11C]PK 11195 and PET.

Benzodiazepinones↗
PubMed1988

Heterozygosity and localisation of normal allelic fragments for an alpha 1-antitrypsin homologous sequence.

Approximately 10 kb downstream of the alpha 1-antitrypsin (AAT) gene is a homologous sequence. Two polymorphisms detected with the restriction enzymes BglII and EcoRI have been reported previously. We describe two additional polymorphisms with the restriction endonucleases TaqI and HindIII and, for all four restriction enzymes, we have mapped the fragments corresponding to the normal alleles in a cosmid clone.

Adult↗
PubMed1988

Multiphase extraction: rapid phase-transfer of [18F]fluoride ion for nucleophilic radiolabeling reactions.

In multiphase extraction [18F]fluoride ion for radiolabeling is recovered from target water by passage through a small column of microporous polymer impregnated with a lipophilic cryptand or quaternary ammonium salt. The 18O enriched water can be recovered for reuse. The [18F]fluoride ion-pair is eluted from the column by a small volume of acetonitrile or other organic solvent. Evaporation of the acetonitrile removes traces of water to yield a reactive ion pair for nucleophilic radiofluorination reactions. A wide range of ion-pairs based on K+ or NH+4 cryptands or quaternary ammonium salts can be employed. The method was applied to the synthesis of [18F]FDG.

Deoxyglucose↗
PubMed1988

A captive solvent method for rapid N-[11C]methylation of secondary amides: application to the benzodiazepine, 4'-chlorodiazepam (RO5-4864).

[11C]4'-Chlorodiazepam (RO5-4864), for PET studies of peripheral benzodiazepine receptors, was synthesized by alkylation of 1-desmethyl-4'-chlorodiazepam, in a small volume of acetone adsorbed on acrylic yarn, with [11C]methyl iodide in the injection loop of a liquid chromatograph. The reaction mixture was introduced directly onto a small, disposable alumina chromatographic column. Elution with pentane:ethanol gave a product of high chemical and radiochemical purity. A simple heating and cooling device for the injection loop is described.

Benzodiazepinones↗
PubMed1987

Deoxyribonucleic acid (DNA) polymorphism of the alpha 1-antitrypsin gene in chronic lung disease.

Specific gene probes were used to study restriction fragment length polymorphisms of the human alpha 1-antitrypsin gene. A polymorphism due to loss of a recognition site for the restriction enzyme Taq I was identified in eight of 42 patients with bronchiectasis and nine of 49 patients with pulmonary emphysema, none of whom had alpha 1-antitrypsin deficiency. Among a control group without lung disease the polymorphism was significantly less frequent, being found in only five of 101 apparently healthy blood donors. The deoxyribonucleic acid (DNA) polymorphism was also present in two of 14 unrelated patients with alpha 1-antitrypsin deficiency, indicating a lack of association with any specific alpha 1-antitrypsin protein phenotype. The polymorphism identified in this study may be a new marker for genetic predisposition to chronic lung disease.

Adolescent↗
PubMed1982

Biochemical aids to the staging of breast cancer.

Up to fifteen plasma proteins were measured before treatment in 249 women presenting with lumps in the breast. Concentrations showed considerable overlap between the various clinical stages, and were often normal even in metastatic disease. A discriminant function is proposed, based on measurement of C-reactive protein, beta 2-microglobulin, carcinoembryonic antigen and ferritin and calculation of a score for each subject. High-risk scores resulted for all 18 patients with Stage 4 (i.e., metastatic) disease, and the number of Stage 1 patients attaining high scores was consistent with the reported incidence of development of metastases in such a group. Follow-up studies are in progress.

Blood Proteins↗
PubMed1981

Standardization of immunochemical determinations of serum albumin.

When we compared four commercially available preparations of human serum albumin with the human serum standard IFCC 74/1 by radial immunodiffusion, by immunoprecipitation turbidimetry, by laser nephelometry, and by "rocket" immunoelectrophoresis, three of the preparations gave almost "theoretical" results with the immunoprecipitation turbidimetric method. Results by the other three methods tended inconsistently to be low. Four pools of normal human serum were also analyzed for albumin by these four immunochemical methods, again with IFCC 74/1 as the reference standard. The results were virtually identical with those obtained by fractionation with 1.8 mol/L sodium sulfate and determination of protein nitrogen in the filtrate. We suggest that a combination of (a) fractionation of a pool of normal human serum in this way and (b) critical comparison with selected commercial preparations of human serum albumin will permit standardization of the serum albumin determination.

Humans↗
PubMed1978

Synthesis and gastrointestinal pharmacology of some 15- and 16- modified (+/-)-11-deoxyprostaglandins.

The synthesis and gastrointestinal pharmacology of some 11-deoxyprostaglandin E1 analogues are described with results analysed for selectivity from side effects. 11-Deoxygenation reduced potency relative to PGE2 but, as has been reported for natural PGs, 15- or 16-methyl analogues were more potent than the unsubstituted parent compound in the order 16-methyl greater than 15-methyl greater than 16,16-dimethyl. The results suggest that a complex interaction between C-15 and C-16 in methyl analogues affects their profile of activity, but that none of the modifications studied conferred a substantial potency or selectivity advantage over PGE2.

Animals↗