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Biomedical subjects

P M Shaw

Publications and source records attributed to P M Shaw.

30 records · Page 2Linked to original sources

Purification and characterization of an anticonvulsant-induced human cytochrome P-450 catalysing cyclosporin metabolism.

A form of human hepatic microsomal cytochrome P-450 (P450hA7) with subunit Mr 50,400 has been purified from an epileptic who had been receiving long-term treatment with anticonvulsant drugs. P450hA7 metabolized the immunosuppressant drug cyclosporin A and the dihydropyridine calcium channel antagonist nifedipine, but did not metabolize a similar dihydropyridine drug, nicardipine, nor a series of alkoxyresorufin model substrates. The hepatic microsomal concentration of P450hA7 was higher in five individuals who had been receiving long-term anticonvulsant treatment than in any of 21 individuals who had not been similarly treated. The mean P450hA7 concentration in the treated individuals was 5-fold higher than the mean concentration in the untreated individuals. It is concluded that P450hA7 is a member of the cytochrome P450III family which is induced by anticonvulsant drugs in man.

Adult↗

Monoclonal antibodies against human cytochrome P-450 recognizing different pregnenolone 16 alpha-carbonitrile-inducible rat cytochromes P-450.

Six murine monoclonal antibodies against human hepatic cytochrome P-450 have been raised, using human liver microsomes (microsomal fractions) or semi-purified human cytochrome P-450 as immunogen. All six antibodies recognized the same highly purified of human liver cytochrome P-450 of molecular mass 53 kDa and gave rise to a single band at 53 kDa on immunoblots of human liver microsomes from 11 individuals. The antibodies also recognized proteins at 52 kDa and 54 kDa on immunoblots of control and induced male-rat liver microsomes, showing four different banding patterns. Antibodies HL4 and HP16 recognized a 52 kDa protein that was only weakly expressed in untreated rats and which was strongly induced by pregnenolone 16 alpha-carbonitrile (PCN) but not by phenobarbitone (PB), 3-methylcholanthrene (3MC), isosafrole (ISF), Aroclor 1254 (ARO), clofibrate or imidazole. HP10 and HL5 recognized a constitutive 52 kDa protein that was weakly induced by PCN but not by the other agents and was suppressed by 3MC and ARO. HP3 recognized a 54 kDa protein that was undetectable in control rats but was strongly induced by PB, PCN, ISF and ARO. HL3 appeared to recognize a combination of the proteins recognized by the other antibodies plus a 54 kDa protein that was weakly expressed in control rats. The constitutive proteins recognized were male-specific.

Animals↗

Social phobia: a comparative clinical study.

Eighty-seven people with the symptom of social phobia were compared with 57 people with the symptom of agoraphobia to determine whether these symptoms were part of distinct syndromes. Comparisons were made on demographic, clinical and questionnaire data. Significant differences were found on important variables. The social phobics were younger and more often male, unmarried, and from social classes I and II. The pattern of phobic situations was different in the two groups and so was the pattern of autonomic symptoms experienced in these situations. Symptoms visible to others were more frequent among social phobics. Fainting was more frequent among the agoraphobics.

Adolescent↗

Imaginal flooding and exposure to real phobic situations: treatment outcome with agoraphobic patients.

Each of thirty-six female agoraphobic out-patients were treated by one of three methods: 8 sessions of imaginal flooding followed by 8 sessions of practice in the real situation; 16 sessions of combined flooding and practice; or 16 sessions of practice alone. Three therapists treated equal numbers of patients in each group, and there was some evidence that patients' response varied according to the therapist seen, irrespective of treatment group. There were no significant differences between treatment groups after 8 sessions, 16 sessions or on six-month follow-up. It is concluded that there are no long-term differences between the effects of treatments involving exposure to either imaginal or real phobic situations or to a combination of both, provided that patients are encouraged to practise between sessions.

Agoraphobia↗

Imaginal flooding and exposure to real phobic situations: changes during treatment.

This paper reports the results of measures taken during treatment in the study of imaginal flooding and exposure to real phobic situations previously described by Mathews, Johnston, Lancashire, Munby, Shaw and Gelder (1976). On weekly measures of change of similar reduction in phobic behaviour in all treatments was found, confirming the previous findings. Differences in therapist effectiveness were also confirmed. On measures of the immediate effects of treatment, exposure to the phobic situation had consistent positive effects, imaginal flooding had little or no detectable effect. It is proposed that the treatments studied differ in their immediate effects on phobic behaviour but also have the common effect of facilitating counterphobic behaviour outside the treatment situation, and that this is the main agent of therapeutic change.

Anxiety↗

Teaching the doctor-patient relation to medical students. Learning experience in a behaviour therapy clinic.

The results of a 2-year trial of teaching medical students in a phobia clinic are described. This has been found a useful experience by the students, particularly as an introduction to the doctor-patient relation. The success rate and attitude of patients justified this experiment, and there might be an indication for extension to other teaching and possibly regional hospitals. The long-term benefits to the medical student are discussed.

Attitude↗

Cytochrome P-450 localization in normal human adult and foetal liver by immunocytochemistry using a monoclonal antibody against human cytochrome P-450.

Immunocytochemical studies with a monoclonal antibody (MAb-HL3), which recognises a major isozyme of human hepatic cytochrome P-450, have demonstrated this cytochrome in both cryostat and formalin-fixed paraffin-embedded sections of normal human adult liver. Prior trypsin digestion of the formalin-fixed sections prevented staining. There was a zonal distribution of immunoreactive cytochrome P-450, with localization predominantly in the hepatocytes of zone 3 of the hepatic acinus (the centrilobular region). Cytochrome P-450 was also demonstrated in foetal liver, but all foetal hepatocytes contained immunoreactive cytochrome P-450 and there was no zonal distribution of the protein. The biliary epithelium of adult liver contained a small amount of immunoreactive cytochrome P-450 whereas there was no immunoreactivity in the epithelium of foetal bile ducts.

Adult↗