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Biomedical subjects

J D Sutherland

Publications and source records attributed to J D Sutherland.

50 records · Page 3Linked to original sources
PubMed1982

The enzymic and chemical synthesis of ursodeoxycholic and chenodeoxycholic acid from cholic acid.

Three approaches to the synthesis of ursodeoxycholic acid (UDC) from cholic acid have been investigated: (i) oxidation of cholic acid to 3 alpha, 7 alpha-dihydroxy-12 keto-5 beta-cholanoic acid (12K-CDC) with Clostridium group P 12 alpha-hydroxysteroid dehydrogenase (HSDH), isomerization of 12K-CDC to 3 alpha, 7 beta-dihydroxy-12 keto-5 beta-cholanoic acid (12K-UDC) with Clostridium absonum 7 alpha- and 7 beta-HSDH and reduction of 12K-UDC by Wolff-Kishner to UDC; (ii) isomerization of cholic acid to ursocholic acid (UC) by C. absonum 7 alpha- and 7 beta-HSDH, oxidation of UC to 12K-UDC with Clostridium group P 12 alpha-HSDH and Wolff-Kishner reduction of 12K-UDC to UDC; (iii) oxidation of cholic acid to 12K-CDC by Clostridium group P 12 alpha-HSDH, Wolff-Kishner reduction of 12K-CDC to chenodeoxycholic acid (CDC) and isomerization of CDC to UDC using whole cell cultures of C. absonum. In the first two approaches (using cell free systems) the yields of desired product were relatively low primarily due to the formation of various side products. The third method proved the most successful giving an overall yield of 37% (UDC) whose structure was verified by mass spectroscopy of the methyl ester.

Cells, Cultured↗
PubMed1982

The metabolism of primary, 7-oxo, and 7 beta-hydroxy bile acids by Clostridium absonum.

Clostridium absonum was shown to metabolize primary bile acids to give rise to both 7-oxo bile acids and 7 beta-hydroxy (urso) bile acids. At relatively low redox potential (Eh) values, high yields of urso bile acids were achieved (60-75%). If, however, the Eh value of the culture was allowed to rise above approximately -100 mv, the 7-oxo bile acid would tend to predominate (more than 75%) and the "death phase" was accelerated. Growth of C. absonum in sterile graduated cylinders instead of in conventional Erlenmeyer flasks was effective in delaying the rise in Eh value with time (which appears largely due to diffusion of atmospheric oxygen into the medium) and in preserving a higher viable count of organisms. It is proposed that the formation of excess amounts of 7-oxo bile acid is a manifestation of oxygen toxicity and that it could be mediated by an increasing intracellular NADP:NADPH ratio. Additionally, the reaction: primary bile acid in equilibrium oxo bile acid in equilibrium urso bile acid was shown to be partially reversible. When the organisms were grown with [24-(14)C]chenodeoxycholic, -cholic, or -7-keto-lithocholic acid, this reaction could be clearly demonstrated. The addition of an equimolar concentration of deoxycholic acid (which itself is not metabolized) effectively enhanced the rate of bioconversion of cholate and 7-keto-lithocholic, but not chenodeoxycholate (whose rate of bioconversion was the fastest of the three). When the organisms were grown with urso bile acids (ursocholic or ursodeoxycholic) or with 7-keto-deoxycholic acid, very little metabolism occurred unless deoxycholic acid was added which induced formation of primary and keto bile acids. In all cases, formation of oxo bile acid from primary or urso bile acid occurred as the Eh value of the medium rose with time and could thus be delayed by the use of a cylinder instead of a flask for growing the culture. These results were rationalized by demonstrating that induction of 7 alpha- and 7 beta-hydroxysteroid dehydrogenase is strongly mediated by chenodeoxycholic and deoxycholic acids, weakly mediated by cholic and 7-keto-lithocholic acids, and ineffective with 7-keto-deoxycholic, ursocholic, and ursodeoxycholic acids.

Bile Acids and Salts↗
PubMed1980

The British object relations theorists: Balint, Winnicott, Fairbairn, Guntrip.

What I believe to be the essential contribution of this group of analysts may be summarized as follows. The role of object relations has always been a prominent theme in analytic thought and has become much more so in recent years. Instead of grafting the implications of relations onto a theory that started from a different standpoint, what the British group has done is to show that the development of the person has to be conceived as the progressive differentiation of a structure from a unitary matrix that itself interacts at a holistic personal level from the start. While Balint noted clinical data that required this step, he did not put forward a theoretical scheme. Winnicott, who suggested more specifically how the infant's relationships at the earliest stages patterned its whole subsequent personal development, also refrained from following through the theoretical logic of his observations. Fairbairn was the first analyst to expose the questionable logic of a developmental scheme based upon the energic concepts that Freud retained as his theoretical base. Fairbairn's scheme, however, did not account adequately for the earliest developmental stages as these were inferred from the study of regressive states. Guntrip, making full use of Winnicott's views, has sought to make good this limitation. The British group does not presume to have made anything like an adequate conceptual map for the development of the psyche. The theoretical problems are far too complex for that. They have, however, shown a fruitful direction and have influenced many areas of contemporary psychoanalytic thought.

Ego↗
PubMedDate not supplied

Do diabetics remember all they have been taught? A survey of knowledge of insulin-dependent diabetics.

A questionnaire survey of 182 insulin-dependent diabetics aged 12-73 years attending a District General Hospital outpatient clinic revealed limitations in the understanding of their disease, with gaps in their knowledge on most aspects of diabetic management, including simple metabolic details, use of insulin, hypoglycaemic reactions, effects of exercise and illness, urine testing, and diet. Only 4 patients (2%) answered all 34 questions correctly and only 27 (15%) answered 11 key questions accurately. The total number of 'knowledgeable' patients who achieved a score of at least 28 in all, including 9 or more key questions correct, was 96 (53%). The degree of knowledge of our patients was unrelated to age, duration of diabetes, place of original diabetic education or degree of diabetic control as measured by blood glucose or HbA1 levels.

Adolescent↗