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A Burchell

Publications and source records attributed to A Burchell.

162 records · Page 9Linked to original sources
PubMed1982

Practical thoughts on cost-benefit analysis and health services.

Cost-benefit analysis is fast becoming--if it is not already--an essential tool in decision making. It is, however, a complex subject, and one in which few doctors have been trained. This paper offers practical thoughts on the art of cost-benefit analysis, and is written for clinicians and other medical specialists who, though inexpert in the techniques of accountancy, nevertheless wish to carry out their own simple analyses in a manner that will enable them, and others, to take effective decisions.

Cost-Benefit Analysis↗
PubMed1977

Regional properties of dorsal and ventral hippocampus in suppression of intralaminar thalamic unit responses.

In chloralose-anaesthetized, Flaxedil-paralysed cats, the suppression of extra-lemniscal thalamic units by dorsal and ventral hippocampus was investigated. Unitary responses to test somatic stimuli, recorded in centrolateral and neighbouring thalamic nuclei, were interacted with conditioning electric stimulation in different regions around the hippocampal arch, including parahippocampal gyrus (entorhinal and retrosplenial areas). Stimulation of dorsal (dhc) and ventral (VHC) hippocampus suppressed roughly equal proportions of responses. However, within each of DHC and VHC, effectiveness depended on the region stimulated. In DHC, fields CA1 and CA3, subiculum (SUB), and retrosplenial area, but not field CA4 or dentate gyrus, usually suppressed extralemniscal units at currents below 1.0 mA. In VHC, the most effective regions were entorhinal cortex, CA3, and CA4 with dentate gryus (FD), while stimulation of CA1 or subiculum was almost ineffective, at currents below 1.0 mA. In VHC, the regions were ranked for effectiveness: Entorhinal cortex=CA3 is greater than FD is greater than SUB is greater than CA1. No topographic relationship was found between hippocampal region and thalamic loci for unit suppression. Lemniscal-type unit responses in ventrobasal thalamus were unaffected by stimulation of the hippocampus or parahippocampal gryus. Interruption of the fornix-fimbria system prevented suppression elicited from CA1 of DHC, or from CA3 but not FD of VHC. It had no effect on suppression elicited from retrosplenial or entorhinal cortex. Hippocampal regional variation of effectiveness in suppressing extralemniscal pathways may contribute to the differential behavioural involvements reported for different hippocampal structures.

Animals↗
PubMed1977

Human mitochondrial malic enzyme variants: properties of the different polymorphic forms.

1. The human mitochondrial malic enzyme polymorphism was found to exist in the Scottish population with similar allele frequencies to those reported previously for Caucasian populations. 2. The mitochondrial malic enzyme variants MEM1, MEM2-1 and MEM2 which form the polymorphism have been separated from the cytoplasmic malic enzyme and partially purified by DEAE Sephadex chromatography. 3. The properties of the three mitochondrial malic enzyme variants were examined. No differences were found between the variants in Km for NADP, Km for pyruvate, Mn2+ and Mg2+ activation, Ki for dicumarol, heat stability, pH or ionic strength optimum.

Alleles↗
PubMed1976

Distribution of isoenzymes of the glycogenolytic cascade in different types of muscle fibre.

Distinct isoenzyme patterns of the glycogenolytic enzymes exist in different fibre types. Fast twitch glycolytic and slow twitch oxidative fibres differ in the proportion of the two isoenzymes of cyclic AMP dependent protein kinase and in the type of phosphorylase kinase that is present. Slow twitch oxidative fibres and cardiac fibres resemble one another in these two respects, but differ in that the type I phosphorylase of cardiac muscle is absent in slow twitch oxidative fibres. In all examples, the functional differences between the isoenzymes seem to be related to the regulatory rather than the catalytic behavior of the molecules. In the case of cyclic AMP dependent protein kinase and phosphorylase kinase, it is a regulatory subunit that appears to be affected [16,23], while in the case of phosphorylase, the type I isoenzyme is known to have a five to eight-fold Ka for the allosteric activator 5' AMP [6]. However, the precise physiological significance of these differences remains to be elucidated.

Animals↗
PubMed1976

The molecular basis of skeletal muscle phosphorylase kinase deficiency.

The molecular basis of phosphorylase kinase deficiency was investigated in ICR/IAn mice, which show less than 0.2% of normal activity in skeletal muscle (Cohen, P.T.W. and Cohen, P., 1973). The genetics of the deficiency indicate it is a single gene defect on the X-chromosome (Lyon, J.B., 1970). Phosphorylase kinase was purified from skeletal muscle of a control strain, C3H/He-mg, by three different procedures. (a) Ammonium sulphate precipitation and gel filtration on Sepharose 4B. (b) Hydrophobic chromatography and affinity chromatography on Sepharose 4B to which antibody to rabbit muscle phosphorylase kinase has been linked covalently. (c) Precipitation from muscle extracts with anti-phosphorylase kinase antibody. All three procedures showed C3H/He-mg phosphorylase kinases were similar to the rabbit muscle enzymes, the structures of the two isoenzymes being (alphabetagamma)4 and (alpha'betagamma)4 respectively. The proportion of the (alpha'betagamma)4 isoenzyme relative to the (alphabetagamma)4 isoenzyme was however about 1:1 in murine muscle compared to about 1:10 in rabbit muscle. Since the alpha and alpha' subunits appear to be distinct gene products, the defect in ICR/IAn mice cannot be caused by a mutation in the genes coding for either the alpha or alpha'chains, or 50% of normal activity would be observed. All three procedures for C3H/He-mg mice failed to detect any of the four subunits alpha, alpha', beta and gamma in ICR/IAn mice, suggesting that all four chains are absent in the deficiency. An allele for the beta-subunit was identified in rabbits, and the inheritance of the allele showed that it was determined by an autosomal gene. Assuming conservation of X-linkage between mammals, the defect in ICR/IAn mice cannot be caused by a mutation in a beta-subunit gene. It is proposed that ICR/IAn mice are defective in a control gene located on the X-chromosome which is required for the expression of structural genes, at least one of which, the gene for the beta-subunit, is located on an autosome. The results imply that interchromosomal transfer of information takes place during the synthesis of phosphorylase kinase.

Amino Acids↗
PubMedDate not supplied

Perinatal factors influencing hepatic glucose-6-phosphatase enzyme activity.

BACKGROUND: At discharge from neonatal units, many preterm infants are vulnerable to preprandial hypoglycemia due to insufficient liver glucose production. In most preterm infants, hepatic glucose-6-phosphatase activity (the terminal step of liver glucose production) remains abnormally low postnatally. OBJECTIVE: To determine what perinatal factors are associated with changes in hepatic glucose-6-phosphatase enzyme activity. STUDY DESIGN: The maximum velocity (Vmax) of the hepatic microsomal glucose-6-phosphatase enzyme, as the dependent variable, was correlated by stepwise multiple regression analysis with clinical data from a consecutive series of 45 preterm infants from a level 3 neonatal unit. RESULTS: Significant factors (p < or = 0.0005) were the presence of pathogenic bacteria isolated from maternal high vaginal swabs (p < or = 0.0000), hyperkalemia regimen, duration of prenatal exposure to ritodrine, and delivery mode. Further analysis revealed that the highest correlation was with positive early post-delivery infant bacterial cultures. CONCLUSION: Perinatal events and clinical interventions modulate key enzyme systems necessary for human adaptation to extrauterine life.

Bacteria↗
PubMedDate not supplied

Glucose-6-phosphatase proteins of the endoplasmic reticulum.

Hepatic glucose-6-phosphatase (G-6-Pase) catalyses the terminal step of hepatic glucose production and it plays a key role in the maintenance of blood glucose homeostasis. Hepatic G-6-Pase is an integral resident endoplasmic reticulum (ER) protein and it is part of a multicomponent system. Its active site is situated inside the lumen of the ER and transport proteins are needed to allow its substrates, glucose-6-phosphate (G-6-P) (and pyrophosphate), and its products, phosphate and glucose to cross the ER membrane. In addition, a calcium-binding protein is also associated with the G-6-Pase enzyme. Recent immunological studies have shown that G-6-Pase (which has conventionally been thought to be present only in the gluconeogenic organs) is present in minor cell types in a variety of human tissues and that its distribution changes dramatically during human development. In all the tissues, enzymatic analysis, direct transport assays and/or immunological detection of the ER glucose and phosphate transport proteins have been used to demonstrate the presence and activity of the whole G-6-Pase system. The G-6-Pase protein is very hydrophobic and has proved difficult to purify to homogeneity. Four proteins of the system have now been isolated and polyclonal antibodies have been raised against them; two have also been cloned. The available sequences, together with topological studies, have given some information about both the topology of the proteins in the ER and the probable mechanisms by which the proteins are retained in the ER.

Amino Acid Sequence↗
PubMedDate not supplied

Evidence for glucuronide (small molecule) sorting by human hepatic endoplasmic reticulum.

The entry of substrates into, and the export of glururonides from, the lumen of hepatic endoplasmic reticulum (ER) in vitro (sealed microsomes) has been measured using radioactivity-labelled materials and a rapid filtration assay. Analysis of liver microsomes from a jaundiced patient showed the accumulation of bilirubin glucuronides within the lumen of the ER. Further analysis of these hepatic microsomes revealed that newly synthesized 1-naphthol glucuronide could exit from the microsomes whereas bilirubin glucuronide was accumulated within the microsomes. These results suggest the existence of mechanisms for the sorting of small molecules, destined for export through bile canalicular or basolateral plasma membranes, by ER. Furthermore, these sorting processes may be regulated by specific transporters within the ER.

Bilirubin↗
PubMedDate not supplied

Low levels of glucose-6-phosphate hydrolysis in the sarcoplasmic reticulum of skeletal muscle: involvement of glucose-6-phosphatase.

Glucose-6-phosphate hydrolysis was measured in a fraction obtained from rabbit fast-twitch skeletal muscle and corresponding to total sarcoplasmic reticulum, as well as in three subfractions containing longitudinal tubules, terminal cisternae or both structures. In all cases the levels of hydrolysis measured both in native and disrupted membranes were approximately 60-100 times lower than the microsomal glucose-6-phosphatase activity of the corresponding livers. In contrast to liver microsomes, most (up to 80%) of the glucose-6-phosphate hydrolysing activity in muscle sarcoplasmic reticulum membranes was not inactivated by pH 5.0 pre-incubation indicating that it was not catalysed by the specific glucose-6-phosphatase enzyme. Osmotically induced changes in light-scattering intensity of sarcoplasmic reticulum vesicles revealed that, in contrast to liver microsomes, sarcoplasmic reticulum vesicles were not selectively permeable to glucose-6-phosphate as mannose-6-phosphate was also permeable and in addition they were poorly permeable to glucose. Immunoblot experiments using antibodies raised against the glucose-6-phosphatase enzyme, and liver endoplasmic reticulum glucose and Pi translocases, failed to detect the presence of these protein components in sarcoplasmic reticulum membranes. Southern blot analysis of reverse transcriptase-polymerase chain reaction products from rat muscle revealed that glucose-6-phosphatase mRNA is present in muscle. Quantification of Northern blot analysis of liver and muscle mRNA indicated that muscle contains less than 2% of the amount of glucose-6-phosphate mRNA found in corresponding livers. We conclude that very low levels of specific glucose-6-phosphatase (e.g. as in liver; E.C. 3.1.3.9) are present in muscle sarcoplasmic reticulum and that the muscle and liver glucose-6-phosphatase systems have several different properties.

Animals↗
PubMedDate not supplied

Developing effective HIV prevention programs for inmates: results from an Ontario-wide survey.

Many studies of the characteristics, behaviours, and prevalence of HIV among those admitted to Canadian correctional facilities indicate that inmates are at increased risk for HIV infection and that they be targeted for HIV interventions. Yet the development and implementation of these programs has been much too slow and, at times, inappropriate to the prison environment. Further, the effectiveness of current and proposed policies and programs must be evaluated to ensure that the goal of reducing HIV transmission is achieved. To address these issues, a team of University of Toronto researchers undertook a study entitled "The Social and Structural Determinants of HIV-Related Risk Behaviours among Prisoners: Implications for Prevention." This study surveyed adult males and females incarcerated in six provincial correctional centres in Ontario. The following provides a brief overview of the study and its results.

AIDS Serodiagnosis↗