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Biomedical subjects

K Dalziel

Publications and source records attributed to K Dalziel.

At least 19 recordsLinked to original sources
PubMed1995

When is it futile for ambulance personnel to initiate cardiopulmonary resuscitation?

OBJECTIVE: To determine whether patients with unexpected prehospital cardiac arrest could be identified in whom ambulance resuscitation attempts would be futile. DESIGN: Review of ambulance and hospital records; detailed review of automated external defibrillator rhythm strips of patients in whom no shock was advised. SETTING: Scottish Ambulance Service; all cardiopulmonary resuscitation attempts after cardiorespiratory arrest during 1988-94 included in the Heartstart Scotland database. SUBJECT: 414 cardiorespiratory arrest patients with no pulse or breathing on arrival of ambulance personnel, no bystander cardiopulmonary resuscitation performed, and more than 15 minutes from time of arrest to arrival of ambulance. Patients were stratified into those with "shockable" and "non-shockable" rhythms. MAIN OUTCOME MEASURES: Return of spontaneous circulation, or survival to reach hospital alive, or survival to discharge, or all three. RESULTS: No patient with a non-shockable rhythm who met the entry criteria for analysis survived a resuscitation attempt. Review of the defibrillator rhythm strips of these patients failed to find any case in which the tracing was deemed compatible with survival. CONCLUSION: On the basis that it would be inappropriate to initiate vigorous resuscitation in patients who can be identified as "dead" and beyond help an algorithm was prepared to guide ambulance personnel.

Algorithms↗
PubMed1988

NADP-linked malic enzyme. Purification from maize leaves, Mr and subunit composition.

1. The isolation of NADP-linked malic enzyme (EC 1.1.1.40) from maize leaves is described, together with studies of its Mr and subunit composition. 2. The enzyme was purified to apparent homogeneity by affinity chromatography on N6-aminohexyl-2',5'-bisphosphoadenosine-agarose, gel filtration with Sephadex G-100 and ion-exchange chromatography on DEAE-Sephadex A-50. A purification of 140-fold with a 30% yield was obtained. 3. A detailed study of the Mr by several methods revealed the existence of different Mr forms in solution. 4. In the presence of dithiothreitol the enzyme appears to be present in triethanolamine buffer, pH 7.5, as a tetramer with a subunit Mr of 60,000 and an S20,w of 10.75 S. 5. In phosphate buffer, pH 7.0, it seems to be a dimer of Mr 120,000 with an S20,w of 7.95 S. 6. In the absence of dithiothreitol, lower-Mr forms were detected by sedimentation-equilibrium and sedimentation-velocity studies in triethanolamine buffer. 7. Results from gel filtration gave Mr values of about 340,000 in both buffers.

Centrifugation, Density Gradient↗
PubMed1987

The effects of isotretinoin on follicular and sebaceous gland differentiation.

Follicular and sebaceous gland cell differentiation was investigated during treatment of acne patients with isotretinoin. Sebaceous glands were significantly reduced in volume and showed decreased metabolic activity as measured by glucose-6-phosphate dehydrogenase and succinic dehydrogenase enzyme activities. There was no measurable change in the volume of follicular duct epithelium or in its metabolic activity during treatment. Metabolic activity was also unchanged in the interfollicular epidermis, contrasting with the effects of another retinoid, etretinate. These findings provide no support for the proposition that alteration in the process of follicular keratinization forms a substantial part of the mode of action of isotretinoin.

Acne Vulgaris↗
PubMed1987

The effect of tetracycline and erythromycin in a model of acne-type inflammation.

The effects of systemically administered oxytetracycline and erythromycin in a guinea pig model of acne-type inflammation were assessed histologically and by tissue measurement techniques. It was found that oxytetracycline significantly reduced the volume and maximum area of inflammation compared with both control and erythromycin treated groups. Oxytetracycline also altered the morphology of the inflammatory infiltrate significantly reducing the proportion of polymorphonuclear leucocytes present. In this model, erythromycin did not alter the inflammatory response but did seem to reduce the amount of transepidermal elimination of inflammatory debris.

Acne Vulgaris↗
PubMed1986

Kinetic studies of 6-phosphogluconate dehydrogenase from sheep liver.

The steady-state kinetics of the oxidative decarboxylation of 6-phosphogluconate catalysed by 6-phosphogluconate dehydrogenase from sheep liver in triethanolamine and phosphate buffers (pH 7.0) have been reinvestigated. In triethanolamine buffer the enzyme is inhibited by high NADP+ concentrations in the presence of low fixed concentrations of 6-phosphogluconate. Data are consistent with an asymmetric sequential mechanism in which NADP+ and 6-phosphogluconate bind randomly and product release is ordered. The pathway through the enzyme--6-phosphogluconate complex appears to be preferred in triethanolamine buffer. Pre-steady-state studies of the oxidative decarboxylation reaction at pH 6.0-8.0 show that hydride transfer is greater than 900 s-1. After the fast formation of NADPH in amounts equivalent to about half of the enzyme-active-centre concentration, the rate of NADPH formation is equal to the steady-state rate. Two possible interpretations are considered. Rapid fluorescence measurements of the displacement of NADPH from its complex with the enzyme at pH 6.0 and 7.0 indicate that the dissociation of NADPH is fast (greater than 800 s-1) and cannot be the rate-limiting step in oxidative decarboxylation. Coenzyme binding studies at equilibrium have been extended to include the determination of the dissociation constants for the binary complexes of enzyme with NADPH and NADP+ at pH 6.0-8.0 and the dissociation constant for NADPH in the ternary enzyme--6-phosphogluconate--NADPH complex in triethanolamine buffer, pH 7.0.

Animals↗
PubMed1986

The chemical mechanism of sheep liver 6-phosphogluconate dehydrogenase. A Schiff-base intermediate is not involved.

[2-18O]Ribulose 5-phosphate was prepared and shown to be converted enzymically by 6-phosphogluconate dehydrogenase from sheep liver into 6-phosphogluconate with complete retention of the heavy isotope. This finding unequivocally excludes the possibility of a Schiff-base mechanism for the enzyme. The involvement of metal ions has already been excluded, and other possible mechanisms are discussed. The enzyme was purified by an improved large-scale procedure, which is briefly described.

Animals↗
PubMed1986

Chemical modification of sheep-liver 6-phosphogluconate dehydrogenase by diethylpyrocarbonate. Evidence for an essential histidine residue.

Sheep liver 6-phosphogluconate dehydrogenase is shown to be inactivated by diethylpyrocarbonate in a biphasic manner at pH 6.0, 25 degrees C. After allowing for the hydrolysis of the reagent, rate constants of 56 M-1 s-1 and 11.0 M-1 s-1 were estimated for the two processes. The complete reactivation of partially inactivated enzyme by neutral hydroxylamine, the elimination of the possibility that modification of cysteine or tyrosine residues are responsible for inactivation, and the magnitudes of the rate constants for inactivation relative to the experimentally determined value for the reaction of diethylpyrocarbonate with N alpha-acetylhistidine (2.2 M-1 s-1), all suggested that enzyme inactivation occurs solely by modification of histidine residues. Comparison of the experimental plot of residual fractional activity versus the number of modified histidine residues per subunit with simulated plots for three hypothetical models, each predicting biphasic kinetics, indicated that inactivation results from the modification of at most one essential histidine residue per subunit, although it appears that other (non-essential) histidines react independently. This histidine is thought to be His-242 and is present in the active site. Evidence in support of its role in catalysis is briefly discussed. Both 6-phosphogluconate and organic phosphate protect against inactivation, and a kinetic analysis of the protection indicated a dissociation constant of 2.1 X 10(-6) M for the enzyme--6-phosphogluconate complex. NADP+ also protected, but this might be due, at least in part, to a reduction in the effective concentration of diethylpyrocarbonate.

Animals↗
PubMed1986

Hair follicle-like change over histiocytomas.

Epidermal hyperplasia is a common finding overlying histiocytomas. Occasionally, a distinctive type of basaloid hyperplasia occurs, with differentiation into primitive hair follicle tissue. This study attempts to characterize this change and determine whether it is associated with any particular clinical or histological feature. Data from patients with histiocytomas displaying induction of pilar epithelium in the epidermis above the lesions was compared with data from controls who did not show this change. The size, site, and duration of histiocytomas were similar in both groups, as were the predominant cell type and distance of histiocytoma from the epidermis. Serial sectioning of histiocytomas showed that the induction of pilar epithelium was a focal phenomenon, often missed in routine sections. It is suggested that histiocytoma cells may produce a "hair organizing mediator."

Epidermis↗
PubMed1984

Inflammation caused by intracutaneous implantation of stratum corneum.

When an epidermoid cyst ruptures, a granulomatous infiltrate develops around the damaged structure. The same is true when other horn-containing cysts release their content into the epidermis. A similar type of inflammation may be observed in the dermis around disrupted and horn-filled follicles in acne vulgaris. In this paper we describe experiments in which a granulomatous inflammation has been produced in guinea-pig skin by the intracutaneous implantation of stratum corneum and discuss the potential of this system as a model for the inflammation in acne.

Acne Vulgaris↗
PubMed1984

Inflammation due to intra-cutaneous implantation of stratum corneum.

Fragments of sterile heel callus and suspensions of human corneocytes were implanted or injected intra-cutaneously into flank skin of guinea pigs. A mixed cellular type of inflammation was produced characterized by the accumulation of polymorphonuclear leucocytes in the early stages and a more granulomatous picture in the later stages. Epithelial hypertrophy and follicular distortion with transepidermal elimination was a frequent accompaniment. Immunoglobulins and the complement component C3 were found scattered irregularly in the inflammation produced and were not thought to be important in the process. The inflammation produced closely emulated the changes observed in acne inflammation and after rupture of horn containing cysts. It is suggested that inflammation caused by the implantation of horn may be suitable for study of human skin disease in which horny debris is released into the dermis, such as acne.

Acne Vulgaris↗
PubMed1983

Kinetics of dissociation of reduced nicotinamide adenine dinucleotide phosphate from its complexes with malic enzyme in relation to substrate inhibition and half-of-the-sites reactivity.

Malic enzyme of pigeon liver binds NADPH at four equivalent enzyme sites and binds Mn2+ and malate each at two sets of "tight" and "weak" sites with negative cooperativity [Pry, T. A., & Hsu, R. Y. (1980) Biochemistry 19, 951-962]. Stopped-flow studies on the displacement of NADPH from the malate-enzyme complexes E4-NADPH4, E4-Mn2(2+)-NADPH4, E4-Mn2(2+)-NADPH4-dimalate, and E4-Mn2(2+)-NADPH4-tetramalate by large excess NADP+ or its analogue phosphoadenosine(2')diphospho(5')ribose show that NADPH dissociates from the binary complex rapidly with a first-order rate constant of 427 s-1. Dissociation from the ternary E4-Mn2(2+)-NADPH4 complex containing two tightly bound Mn2+ ions can be described by a single first-order process with a rate constant of 135 s-1, or more satisfactorily by two simultaneous first-order processes attributable to the reactions of Mn2+-deficient (k congruent to 427 s-1) and Mn2+-liganded (k = 96 s-1) subunits. The latter equals twice the maximum steady-state turnover rate of 53.2 + 3.0 s-1 assigned to dissociation of the reduced nucleotide from transient E-Mn2+-NADPH, and this 2:1 ratio strongly supports our proposed "half-of-the-sites" model [Hsu, R. Y., & Pry, T. A. (1980) Biochemistry 19, 962-968]. Dissociation from the E4-Mn2(2+)-NADPH4-dimalate complex (k = 100 s-1) follows only the slower process, suggesting that occupancy of malate at two sites tightens enzyme-bound NADPH on the adjacent sites. Binding of malate at two additional weak sites yields E4-Mn2(2+)-NADPH4-tetramalate and a NADPH dissociation rate constant of 2.69 s-1. The 97% decrease in NADPH dissociation parallels the observed 93% maximal inhibition by malate and is the cause of substrate inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗
PubMed1982

On the mechanism of NADP+-linked isocitrate dehydrogenase from heart mitochondria. I. The kinetics of dissociation of NADPH from its enzyme complex.

The kinetics of dissociation of NADPH from its complex with isocitrate dehydrogenase, and from the abortive complex of enzyme, Mg2+, isocitrate and NADPH, have been studied in phosphate and triethanolamine buffers by means of rapid fluorescence measurements. The reactions are complex, and it is suggested that a conformational equilibrium of each of the complexes is involved, and that this conformational change is also responsible for a slow approach to the steady-state rate of oxidative decarboxylation observed previously in triethanolamine buffer under certain conditions (K. Dalziel, N. McFerran, B. Matthews & C.H. Reynolds, Biochem. J. 171, 743-750 (1978) ). It is concluded that release of free NADPH product is not the rate-limiting step in oxidative decarboxylation in the steady state. The validity of the ligand displacement method used to measure the dissociation kinetics of the enzyme-NADPH complex has been studied by computer simulation.

Animals↗
PubMed1982

On the mechanism of NADP+-linked isocitrate dehydrogenase from heart mitochondria. II. The transient-state kinetics of the oxidative decarboxylation of isocitrate.

The kinetics of a single turnover of enzyme-catalysed oxidative decarboxylation have been studied by mixing a stoichiometric complex of enzyme, isocitrate and Mg2+ with large concentrations of NADP+ in a stopped-flow apparatus, and monitoring the formation of NADPH by fluorescence measurements. A transient is revealed that exhibits enhanced nucleotide fluorescence and is not detectable by light absorption measurements. The results obtained with the largest NADP+ concentrations, such that the product NADPH is largely displaced from its enzyme complex, show that a step that precedes the release of free NADPH is rate-limiting in the oxidative decarboxylation reaction under conditions of catalytic cycling. The rate constants for this step, tentatively identified as the formation of the complex of enzyme, Mg2+ and NADPH from a precursor NADPH-containing complex, and for the dissociation of NADPH from this complex have been estimated from the integrated rate equation for a simple model for the product phase of the reaction, by methods of nonlinear regression analysis. In line with the conclusions from the preceding paper, it is suggested that formation of an abortive complex of enzyme, Mg2+, isocitrate and NADPH under catalytic cycling conditions serves to by-pass the potentially rate-limiting dissociation of NADPH from the enzyme-Mg2+-NADPH complex.

Animals↗
PubMed1981

Glyceraldehyde-3-phosphate dehydrogenase.

Conflicting experimental evidence of the pathway of catalysis for the enzyme from rabbit, pig and lobster muscle tissues is reviewed. Transient kinetic studies with the enzyme from rabbit muscle are presented. The results are shown to be consistent with the double-displacement mechanism of catalysis originally proposed by Segal & Boyer (1953). The rate constant for combination of the aldehyde form of the substrate with the NAD+ complex of the enzyme is about 3 X 10(7) M-1 S-1, and for all four subunits of the molecule the rate constant for hydride transfer in the ternary complex formed is greater than 10(3) S-1, consistent with their simultaneous participation in catalysis. Recent steady-state kinetic studies with the rabbit muscle enzyme, in contrast to earlier studies, also provide evidence to support the Segal-Boyer pathway if the kinetic effects of the negative cooperativity of NAD+ binding are taken into account. Experimental data for the binding of NAD+ to the enzyme from muscles and from Bacillus stearothermophilus, and their interpretations, are also briefly reviewed. The information currently available from X-ray crystallography regarding the structures of holoenzyme and apoenzyme from B. stearothermophilus and lobster muscle is outlined.

Animals↗