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T Shaw

Publications and source records attributed to T Shaw.

85 records · Page 5Linked to original sources
PubMed1975

Observations on the epidemiology of ephemeral fever in Kenya.

Ephemeral fever antibody was found in domestic cattle in Kenya across a wide range of ecological zones, from highland forests and grasslands to desert and semidesert thorn scrub. Antibody was found in several species of game animals, notably waterbuck and buffalo, where over 50% of the samples showed antibody to EF. Evidence was obtained to show that the virus had been cycling in these wild ruminant populations between epizootics in domestic cattle.

Animals↗
PubMedDate not supplied

The role of blood platelets in nucleoside metabolism: regulation of megakaryocyte development and platelet production.

In higher vertebrates, different types of blood cells develop from common precursors. Mammals are unique in possessing two types of blood cells--erythrocytes and platelets--which lack nuclei. Although platelets display consistent and easily-recognisable morphological and ultrastructural characteristics and show extreme metabolic and functional versatility, they are not true cells, being produced by fragmentation of giant polyploid precursors called megakaryocytes. At present, the physiological mechanisms which regulate megakaryocyte development and platelet production are not well understood. Platelets are actively involved in metabolism of purine derivatives and a significant platelet role in pyrimidine metabolism has also been demonstrated (see previous papers). Here an attempt is made to integrate information about platelet involvement in nucleic acid precursor metabolism with current concepts of haematopoiesis, particularly megakaryocyte development and platelet production. It is concluded (i) that megakaryocytic cells are immediate descendents of haematopoietic stem cells which have become polyploid as a result of genetic damage or metabolic imbalances, (ii) megakaryocytes and platelets are the ultimate regulators of stem cell development because they control the availability of thymidine and (iii) that the production of megakaryocytes and platelets is a physiological safety mechanism which prevents fixation of genetic damage and protects other cells from potentially cytotoxic and genotoxic stimuli.

Animals↗
PubMedDate not supplied

The role of blood platelets in nucleoside metabolism: assay, cellular location and significance of thymidine phosphorylase in human blood.

The enzyme thymidine phosphorylase (thymidine: orthophosphate deoxyribosyltransferase, EC 2.4.2.4), which plays a crucial role in nucleic acid metabolism in both prokaryotic and eukaryotic cells by regulating the availability of thymidine, is present in mammalian blood. Here we describe a simple, rapid HPLC-based micromethod for the assay of blood thymidine phosphorylase. We have arbitrarily defined 1 unit of blood thymidine phosphorylase activity as the activity required to produce a 1-nM increment in the plasma concentration of thymine after incubation for 1 h at 37 degrees C with a saturating concentration of exogenous thymidine. In normal adults, whole (peripheral venous) blood thymidine phosphorylase activity with blood cells intact was 64 +/- 11 units (mean +/- S.D., n = 20, range 45-89). The apparent Michaelis constant for thymidine was of the order of 10(-4) M but varied nearly 5-fold between different individuals. Activity increased when blood cells were permeabilised or lysed with non-ionic detergents, implying that thymidine phosphorylase is an intracellular enzyme which may be influenced by exogenous as well as intracellular factors. When blood from normal donors was fractionated, thymidine phosphorylase activity consistently co-isolated with platelets. Whole-blood thymidine phosphorylase activity correlated well with platelet parameters. Although thymidine phosphorylase activity was also detected in plasma and serum, the small size and notorious fragility of platelets suggest its platelet origin. Blood from leukaemic donors showed significantly increased thymidine phosphorylase activity compared to normal controls (mean activity +/- S.D. was 96 +/- 27 units; range 58-140, n = 8). Thymine formation from thymidine was temperature- and pH-dependent in whole blood. 2'-Deoxyuridine and 3 of its 5-halogenated analogues (but not 3'-azido-3'-deoxythymidine (AZT), were catabolised by blood thymidine phosphorylase, even during blood clotting at room temperature. Assumptions about in vivo concentrations of these compounds should therefore be interpreted cautiously. In the presence of high concentrations of thymine and suitable deoxyribose donors, small amounts of thymidine were formed in some blood samples, so it is conceivable that thymidine catabolism may be reversible in vivo under some circumstances.

Blood Platelets↗
PubMedDate not supplied

The role of blood platelets in nucleoside metabolism: regulation of platelet thymidine phosphorylase.

Blood platelets are the smallest cellular elements in mammalian blood. Because of their small size, platelets have an unusually large surface area: volume ratio and are exquisitely sensitive to a multitude of physiological and environmental stimuli. Platelets lack nuclei, but most possess functional mitochondria and remain capable of both anaerobic and aerobic energy metabolism, for which they utilise a variety of substrates including many which are cytotoxic and genotoxic for other (nucleated) cells. Nucleic acid precursors are amongst the potentially genotoxic compounds for which platelets have an apparently insatiable appetite. In particular platelets actively scavenge adenine and adenosine, which they convert to nucleotides and use in energy metabolism, but they also rapidly phosphorylase thymidine and liberate thymine into the extracellular medium. In addition, platelets contain non-metabolisable membrane-bound pools of adenine nucleotides which they secrete in response to strong agonists. Taken together, these observations suggest that blood platelets play an important role in nucleic acid precursor metabolism. In the previous paper we have shown that most thymidine phosphorylase activity present in normal human blood resides in the cytoplasm of platelets. Here we demonstrate that this enzyme activity can be modulated in a dose-dependent fashion, not only by substances recognised as platelet agonists and antagonists, but also by some compounds which are considered to be toxic, mutagenic and/or carcinogenic. The data which we present provide additional support for our previous suggestion that platelets regulate thymidine homeostasis and further imply that this is the normal, physiological, platelet function. Preliminary results suggest that assays of blood platelet thymidine metabolism may provide data with a wide variety of applications.

Alcohols↗
PubMedDate not supplied

Critical appraisal of cerebral blood flow measured from brain stem and cerebellar regions after 133 Xe inhalation in humans.

Validity of regional blood flow (rCBF) measurements recorded over the human posterior fossa after 133Xe inhalation was tested. Recording of counts from both brain stem and cerebellum (BSC) was reproducible and contamination by counts derived from surrounding anatomical structures was low and no greater than that found over hemispheres. BSC values were F1 = 99 +/- 19 ml/100g brain/min, F2 = 17 +/- 4 in reasonable agreement with data reported from experimental animals. BSC flow values showed significant correlation with the state of awareness as judged by clinical and EEG evaluation with lowest F1 values in semicoma and step increases in stupor, non-REM sleep, drowsiness, rest, activation, REM sleep and highest values during focal and generalized epileptic seizures.

Adolescent↗
PubMedDate not supplied

Mapping local blood flow of human brain by CT scanning during stable xenon inhalation.

Non-invasive methods are described for estimating local cerebral blood flows (LCBF) and partition coefficients (L lambda) during inhalation of 35% stable xenon gas (Xes) in oxygen during CT scanning. After denitrogenation by 100% oxygen breathing, 35% Xes is breathed for 7-8 minutes to minimize subanesthetic effects. Mean changes in brain Hounsfield units extrapolated to 15 minutes were 7.7 units for white matter and 5.3 units for gray matter. They were measured from volumes 80 cubic mm (10 mm2 area x 8 mm), or larger with an EMI 1010 scanner at 1 minute intervals. These data were used for computing LCBFs and L lambdas. Irradiation measured at the center of brain slices was 1 rad per minute. To calculate L lambdas about 6 exposures are necessary, thereafter, each 1 minute scan provides LCBF measurements for 2 adjacent 8 mm slices. Reproducibility for LCBF was r = 0.85 (P less 0.001). Mean L lambdas were 0.86 +/- 0.08 for gray and 1.34 +/- 0.10 for white matter. Normative mean flows (mls/100 g brain/min) were: basal ganglia = 79.6 +/- 9.3, cortex = 82.3 +/- 8.5, white matter = 29.2 +/- 5.9, midbrain tegmentum = 94.3 +/- 14.8, cerebellar cortex = 80.1 +/- 10.9, dorsal pons = 89.3 +/- 4.7, brachium pontis = 35.0 +/- 4.2. Subject finger exercises produced increases of LCBF in contralateral pre-central and post-central gyri. Eye closure decreased flow values limited to the visual system. Gray matter flow values diffusely decreased in non-REM sleep but increased above normal in REM sleep. Cerebral infarction and hemorrhage resulted in zones of zero flow with borders having reduced lambdas and low flows attributed to edema.

Adult↗
PubMedDate not supplied

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Adult↗