Search PubMed⌕ Search

Biomedical subjects

M E Jones

Publications and source records attributed to M E Jones.

At least 163 records · Page 9Linked to original sources
PubMed1992

Climatic temperature and variation in the incidence of sudden infant death syndrome between the Australian states.

OBJECTIVE: To describe the relationship between climatic temperature and the incidence of sudden infant death syndrome (SIDS) for the Australian States and examine the extent to which differences in climatic temperature might explain the regional variation of SIDS in Australia. DESIGN: Case series study. A generalised linear model was used to model the association between monthly average temperature and the incidence of SIDS. SETTING: The report is population based. Data are available from all Australian States. SUBJECTS: Cases of SIDS from birth to less than 12 months of age occurring in Queensland (1981-1987), New South Wales (1981-1987), Victoria (1984-1987), Tasmania (1975-1989), South Australia (1980-1989), and Western Australia (1980-1988). RESULTS: Every one degree Celsius decrease in average monthly temperature within the range 9 degrees C to 25 degrees C is associated with a 10.6% (95% confidence interval, 9.6%-11.7%) increase in the incidence of SIDS. Climatic temperature accounts for 84% of the interstate variation in the rate of SIDS. After controlling for the effect of temperature, a significant overall difference in SIDS incidence remains (P less than 0.0001) for the Australian States. CONCLUSION: Climatic temperature accounts for most but not all of the regional variation of SIDS incidence in the Australian States. The remaining variation may reflect differences in the maternal and infant characteristics of the State populations.

Australia↗
PubMed1992

Sudden infant death syndrome: factors contributing to the difference in incidence between Victoria and Tasmania.

OBJECTIVE: To examine how much of the difference in incidence of sudden infant death syndrome (SIDS) between Tasmania and Victoria could be accounted for by the effect of differing climatic temperature and the effect of the differing prevalence of maternal and infant characteristics in the two State populations. DESIGN: A two population ecological comparison. Two previously published predictive models were applied to quantify the contribution of several factors to the higher incidence of SIDS in Tasmania compared with Victoria. SETTING: A population based study involving the two Australian States of Tasmania and Victoria. PATIENTS: The characteristics of the 1985 to 1987 live birth cohorts of Tasmania and Victoria were examined. Cases were defined as all infants dying in 1985 to 1987 whose cause of death was stated as SIDS. RESULTS: The rate of SIDS for Tasmania and Victoria 1985 to 1987 was 3.76 per 1000 live births and 2.18 per 1000 live births respectively. Adjustment of the Tasmanian rate for the effect of the interstate difference in climatic temperature resulted in a lower Tasmanian rate of 2.92 per 1000 live births. Adjustment for the effect of interstate differences in maternal age, birthweight, infant sex, month of birth and intention to breast-feed at hospital discharge decreased the Tasmanian rate to 2.47 per 1000 live births. CONCLUSION: Approximately 82% of the interstate difference in SIDS incidence between Tasmania and Victoria from 1985 to 1987 can be accounted for by differences in climatic temperature, maternal age, birth-weight, infant sex, month of birth and feeding intention at hospital discharge.

Adult↗
PubMed1992

Thermal environment and sudden infant death syndrome: case-control study.

OBJECTIVE: To compare the thermal environment of infants who died of the sudden infant death syndrome with that of age matched control infants. DESIGN: Case-control study. Infants who died were matched with two controls, one for age and one for age and birth weight. Thermal measurements were conducted at the death scene for cases and at the scene of last sleep for control infants, who were visited unexpectedly within four weeks of the index infant's death on a day of similar climatic conditions. A follow up questionnaire was administered to parents of cases and controls. SETTING: The geographical area served by the professional Tasmanian state ambulance service, which includes 94% of the Tasmanian population. SUBJECTS: 41 infants died of the sudden infant death syndrome at home; thermal observations at death scene were available for 28 (68%), parental questionnaire data were available for 40 (96%). 38 controls matched for age and 41 matched for age and birth weight. RESULTS: Cases had more excess thermal insulation for their given room temperature (2.3 togs) than matched controls (0.6 togs) (p = 0.009). For every excess thermal insulation unit (tog) the relative risk of the sudden infant death syndrome was 1.26 (95% confidence interval 1.05 to 1.52). The average thermal bedding value calculated from parental recall was similar to that observed by attendant ambulance officers (mean difference = 0.4 tog, p = 0.39). Cases were more likely to have been found prone (odds ratio 4.58; 1.48 to 14.11). Prone sleeping position was not a confounder or effect modifier of the relation between excess thermal insulation and the syndrome. CONCLUSIONS: Overheating and the prone sleeping position are independently associated with an increased risk of the sudden infant death syndrome. Further work on infant thermal balance and sudden infant death is required and guidelines for appropriate infant thermal care need to be developed.

Bedding and Linens↗
PubMed1992

Circulating CD34+ cells: an adverse prognostic factor in the myelodysplastic syndromes.

As part of an epidemiological survey of myelodysplastic syndromes (MDS) in southern Tasmania, 62 MDS patients identified over a 2 year period were tested for the presence of CD34, the human progenitor cell antigen (HPCA), in their peripheral blood. The results were correlated with transformation to acute myeloid leukemia (AML) and patient survival, and CD34+ status was compared as a prognostic indicator with Bournemouth score, cytogenetics, and CFU-GM colony growth which were also assessed. Circulating CD34+ cells were found in 23 of the 62 MDS patients; 9 of the 23 patients with circulating CD34+ cells transformed to AML, as compared with none of the 39 CD34 negative patients (P less than 0.0001); and 11 of the 23 patients with circulating CD34+ cells were dead at the end of the 2 year period, as opposed to 6 of the 39 with no CD34+ cells (P less than 0.03). The Bournemouth score was also significantly associated with transformation to AML (P less than 0.0001) and poor survival (P less than 0.04). These were the only significant associations of the possible prognostic factors studied with either transformation or survival. In summary, the presence of circulating CD34+ cells was significantly associated with both progression to AML and poor survival and was found to be a better prognostic indicator than cytogenetics or CFU-GM colony growth.

Adult↗
PubMed1992

Orotidylate decarboxylase of yeast and man.

The mechanism for ODCase appears to involve the formation of a zwitterion of OMP and a ylid on decarboxylation. Thiamin pyrophosphate catalyzes various decarboxylation and transfer reactions involving ketone groups because the thiazolium ring with its positively charged N atom can, on the loss of a proton from the adjacent C-2, generate a ylid which adds to carbonyl groups to produce a substrate ylid. The unusual aspect, then, of the ODCase reaction is that the substrate itself becomes the ylid, presumably by gaining a proton from ODCase, which results in a positive charge on the N-1 atom of the pyrimidine ring. It is a zwitterion in the transition state which momentarily becomes a ylid on decarboxylation of OMP which then yields the product, UMP. There is no known cofactor for the ODCase reaction. It will be of interest to discover the groups on the enzyme that aid in formation of the zwitterion and the ylid. Further work on the crystal structure and on the production of altered enzymes (where specific amino acids suspected to be important for the reaction are changed) should reveal more details about this important and novel reaction.

Amino Acid Sequence↗
PubMed1992

Characteristics of the infant thermal environment in the control population of a case-control study of SIDS.

This report examines the thermal environment during last sleep of a control population to investigate how the thermal environment of the infant's bedroom varies by season, external temperature and by certain maternal and infant characteristics. Two age-matched control infants were chosen for each case, one of which was also matched on birthweight. The home visits were not pre-arranged and were matched on climatic conditions, time of year and time period of day for the index case. The initial response rate for controls (n = 108) was 86%. Although there was a large amount of variation in the infant thermal environment, thermal insulation correlated with room temperature (r = -0.44, P = 0.0001) and external temperature (r = -0.30, P = 0.002). The thermal environment of the infant, as defined by excess thermal insulation for room temperature, did not vary by indoor or outdoor temperature, but higher average values were observed in teenage mothers (mean difference = 2.7 tog [95% Cl = 0.3, 5.2]), infants who slept in an adult bed (mean difference = 2.6 tog [-0.1, 5.4]) and infants with an illness (mean difference = 0.8 tog [-0.3, 1.9]). There was a tendency for the thermal environment of infants to be higher and more variable during winter, supporting previous hypotheses that paradoxical overheating may occur in some infants during winter. Further work is required to provide a set of recommendations on the optimal thermal conditions for post-neonatal infants.

Bedding and Linens↗
PubMed1992

Sudden infant death syndrome: seasonality and a biphasic model of pathogenesis.

STUDY OBJECTIVE: This paper examines the relationship between season, age, and the sudden infant death syndrome (SIDS). It provides a theoretical model for the pathogenesis of SIDS and uses it as a framework to consider risk factor mechanism. DESIGN: A case series analysis was used to examine season and age in relation to SIDS and seasonal pattern and age at death distribution of perinatal risk factors. SETTING: The source population for the SIDS cases in this study was all live births in the state of Tasmania, Australia, 1975 to 1987 inclusive. SUBJECTS: Cases were all infants born 1975 to 1987 who died of SIDS on whom birth notification information was available (n = 348). The live birth cohort 1980-87 (n = 55,944) was used as the control population for risk factor identification. MEASUREMENTS AND MAIN RESULTS: The median ages of death for spring, summer, autumn, and winter born infants were 115, 103.5, 91 and 78 days. Spring and summer born infants died at a significantly older median age than winter born infants. The month of birth distribution of SIDS cases did not alter significantly from a uniform, nonseasonal distribution (p greater than 0.25) but month of death was seasonally distributed (p less than 0.01). Premature and low birthweight infants died at an older median age (p less than 0.05) than term and non-low-birthweight infants. An excess of male infant deaths and infant deaths to older mothers occurred during winter (p less than 0.05). CONCLUSIONS: The pathogenesis of SIDS can be represented as a biphasic model with three pathways of risk factor operation. In this study, season influenced the age at death of SIDS infants. We propose that risk factors with a strong seasonal distribution are likely to be operating in the postnatal period.

Female↗
PubMed1992

Algebraic least squares estimates of inhibitor constants.

When the data has a constant coefficient of variation, appropriately weighted least squares estimates of the parameters for competitive inhibition in both enzyme and binding experiments can be obtained algebraically. The algorithms are presented and justified.

Algorithms↗
PubMed1991

Purification and characterization of yeast orotidine 5'-monophosphate decarboxylase overexpressed from plasmid PGU2.

Orotidine 5'-monophosphate decarboxylase (ODCase) has been overexpressed in yeast 15C cells transformed with a plasmid carrying the URA3 gene that encodes ODCase. Twenty g of cells having ODCase activity equal to 30 mg of pure enzyme per liter of cell culture were obtained after 9 h of galactose induction. To remove yeast proteases, a 60-90% ammonium sulfate fractionation step plus the addition of EDTA as an inhibitor of metallopeptidases was necessary. The purification protocol yielded ODCase that was protease-free and stable to storage at 4 degrees C for 16 months. The pure enzyme had a specific activity of 40 units/mg in 50 mM phosphate buffer, pH 6, and could be stored at -20 degrees C in 20% glycerol with retention of full activity for more than 2 years. The enzyme had a Km for orotidine 5'-monophosphate of 0.7 microM at pH 6 and 25 degrees C. The molecular weight of the plasmid-derived ODCase monomer determined by electrophoresis on denaturing polyacrylamide gels was 29,500. ODCase sedimented through sucrose density gradients as a monomer of about 30 kDa at low protein concentration and in the absence of ligands that bind at the catalytic site. An increase in the sedimentation rate could be induced by increasing the ODCase concentration or by adding ligands that are competitive inhibitors. ODCase sedimented in a single band typical of a protein of 46 kDa at the highest protein concentration studied or in the presence of 50 mM phosphate or 933 microM substrate (orotidine 5'-monophosphate) or product (UMP). A dimer sedimenting as a protein of about 64 kDa occurred in the presence of 50 microM 6-azauridine 5'-monophosphate or 2 microM 1-(5'-phospho-beta-D-ribofuranosyl) barbituric acid, competitive inhibitors of ODCase. These results resemble the ligand-induced subunit association of the ODCase domain of bifunctional UMP synthase and support the use of yeast ODCase as a model for ODCases from other species.

Binding, Competitive↗
PubMed1991

Investigation of the enzymatic mechanism of yeast orotidine-5'-monophosphate decarboxylase using 13C kinetic isotope effects.

Orotidine-5'-monophosphate decarboxylase (ODCase) from Saccharomyces cerevisiae displays an observed 13C kinetic isotope effect of 1.0247 +/- 0.0008 at 25 degrees C, pH 6.8. The observed isotope effect is sensitive to changes in the reaction medium, such as pH, temperature, or glycerol content. The value of 1.0494 +/- 0.0006 measured at pH 4.0, 25 degrees C, is not altered significantly by temperature or glycerol, and thus the intrinsic isotope effect for the reaction is apparently being observed under these conditions and decarboxylation is almost entirely rate-determining. These data require a catalytic mechanism with freely reversible binding and one in which a very limited contribution to the overall rate is made by chemical steps preceding decarboxylation; the zwitterion mechanism of Beak and Siegel [Beak, P. & Siegel, B. (1976) J. Am. Chem. Soc. 98, 3601-3606], which involves only protonation of the pyrimidine ring, is such a mechanism. With use of an intrinsic isotope effect of 1.05, a partitioning factor of less than unity is calculated for ODCase at pH 6.0, 25 degrees C. A quantitative kinetic analysis using this result excludes the possibility of an enzymatic mechanism involving covalent attachment of an enzyme nucleophile to C-5 of the pyrimidine ring. The observed isotope effect does not rise to the intrinsic value above pH 8.5; instead, the observed isotope effects at 25 degrees C plotted against pH yield an asymmetric curve that at high pH plateaus at about 1.035. These data, in conjunction with the pH profile of Vmax/km, fit a kinetic model in which an enzyme proton necessary for catalysis is titrated at high pH, thus providing evidence for the catalytic mechanism of Beak and Siegel (1976).

Carbon Isotopes↗
PubMed1991

Iron uptake by human reticulocytes at physiologic and sub-physiologic concentrations of iron transferrin: the effect of interaction with aluminum transferrin.

We have studied the interaction, in vitro, between diferric transferrin (FeTr), aluminum transferrin (AlTr), and human reticulocytes harvested from human placental blood. In particular, we aimed to determine the extent to which the kinetics of AlTr and FeTr differed. Using transferrin labeled with either 59Fe or 125I, the association of radiotracer with reticulocytes, as a function both of time and of transferrin concentration, was examined. Under the conditions of the experiments, the data are consistent with a mechanism involving at least three processes. Two early processes acting in parallel behave as a high-affinity saturable receptor and a low-affinity non-saturable receptor, neither of which distinguish between AlTr and FeTr. In a subsequent process, AlTr and FeTr exhibit different kinetics. This third process may be saturated by FeTr but not by AlTr. Interpreted in terms of a current conventional view of metallo-transferrin uptake, we conjecture that the early parallel processes involve cell surface phenomena including classical transferrin-receptor binding, and that the subsequent process represents events, possibly intracellular, involved in metallo-transferrin dissociation or further iron transport. The extent to which AlTr influences the interaction of FeTr with reticulocytes offers insight into both the normal physiology of iron uptake and the potential for toxicity by aluminum.

Binding, Competitive↗
PubMed1991

Crystallization of yeast orotidine 5'-monophosphate decarboxylase complexed with 1-(5'-phospho-beta-D-ribofuranosyl) barbituric acid.

Using an incomplete factorial experimental design, we have identified conditions for crystallization of yeast orotidine 5'-monophosphate decarboxylase (ODCase) in an unliganded state and complexed separately to two inhibitors: 6-azauridine 5'-monophosphate (aza-UMP) and 1-(5'-phospho-beta-D-ribofuranosyl) barbituric acid (BMP). Crystals of X-ray diffraction quality have been obtained of yeast ODCase complexed with BMP, a putative transition state analog inhibitor (Ki = 8.8 x 10(-12) M). ODCase:BMP complex crystals with a hexagonal rod habit were grown from a solution initially containing 12 mg/ml ODCase (205 microM dimer) plus 450 microM BMP by microdialysis at 4 degrees C against a mother liquor which consisted of 0.1 M Na-PIPES-acetate (pH 6.4), 37.5 microM BMP, 5 mM mercaptoethanol, 1% polyethylene glycol 400, and 2.3 M ammonium sulfate. Crystals were analyzed using precession photography and were assigned to trigonal space group R32 with unit cell dimensions a = b = 115 A, c = 385 A. The crystal density is 1.245 g/cm3 indicating the presence of two ODCase: BMP complex dimers (118 kDa each) per asymmetric unit with a packing density of 2.08 A3/Da and 41% solvent content. The morphological habit of crystals of the ODCase:BMP complex changed when the initial ammonium sulfate concentration was increased in 0.05 M steps from 2.3 to 2.45 M. All of these crystals diffracted to at least 3.0 A resolution over a period of several weeks at room temperature and are isomorphous.

Ammonium Sulfate↗
PubMed1991

Least-squares estimation of enzyme parameters.

The estimation of the enzyme parameters Km and Vmax from initial velocity data, or of analogous parameters in binding or transport experiments may be accomplished by transformation of the data, or by a direct weighted least-squares fit. Although the latter makes better use of the data, the method is complex and may be sensitive to initial parameter estimates. We develop a method which reduces the problem to finding the zero of a continuous function of a single variable.

Computer Simulation↗
PubMed1991

Behavioral correlates of male mating success in a multisire flock as determined by DNA fingerprinting.

The fertility of an individual rooster within a multi-sire flock may be influenced by a number of behavioral considerations, including frequency and timing of matings and the male's position in the social dominance hierarchy. The relationship between behavior and fertility has proven difficult to assess, however, because there are a limited number of heritable morphological traits that can be used to determine paternity. The objectives of the present study were to use DNA fingerprinting to determine paternity in domestic fowl and to assess some behavioral and physiological correlates of mating success. Sixty day-old chicks from each of two commercial breeds, DeKalb White Leghorn (L) and Warren Color-Sexed (W), were reared in either same-breed or mixed-breed groups. At 43 wk of age, all females and six randomly selected males were mixed into one large pen. Male aggressive and mating behaviors were recorded over a 4-mo period. Fertility of individual sires was determined by DNA fingerprinting and pedigree analysis of chicks. Dominance rank and the frequencies of both completed matings and mating attempts were positively correlated with fertility (P less than .01). In addition, wing flapping was correlated with both dominance (P less than .001) and fertility (P less than .05). There was no correlation between fertility and plasma testosterone. There were breed effects on dominance status, with W dominating L. Multiple paternity was demonstrated in 4 out of 10 families by DNA fingerprinting. The present study is the first one to demonstrate a correlation between dominance and fertility in a flock containing several males of the same breed and morphology.

Animals↗
PubMed1991

Evaluation of right ventricular regional perfusion with technetium-99m-sestamibi SPECT.

To evaluate technetium-99m-sestamibi as a right ventricular perfusion imaging agent, 25 normal volunteers and 25 patients with suspected coronary disease were studied with both sestamibi and thallium-201 SPECT. All patients underwent cardiac characterization. Compared to thallium-201 images, visualization of the right ventricle was superior for sestamibi in all cases. After computer masking of the left ventricle, count profiles for each 6-mm right ventricular short-axis slice were extracted and plotted in a bull's-eye type polar map with images normalized to maximal right ventricular counts. On sestamibi right ventricular polar maps, 7 of 11 patients (64%) with right coronary stenosis had fixed or reversible inferior right ventricular defects. None of the 25 volunteers or patients without right coronary stenosis had right ventricular defects (true-negative rate = 100%). We conclude that sestamibi SPECT provides an accurate means to assess right ventricular regional perfusion, with data presentation and interpretation facilitated by the polar map display.

Adult↗
PubMed1990

Pyrroline 5-carboxylate dehydrogenase of the mitochondrial matrix of rat liver. Purification, physical and kinetic characteristics.

The oxidation of proline to glutamate in mitochondria requires two enzymes, proline oxidase and pyrroline 5-carboxylate (P5C) dehydrogenase. In this paper we report an 800-fold purification P5C dehydrogenase from rat liver mitochondria to yield an essentially homogenous protein. The protein, whose Mr is 59,000, is an alpha 2 dimer (Mr = 115,000) in solution with an isoionic point at pH 5.7. The substrates P5C and NAD+ have apparent dissociation constants of 0.16 and 1.0 mM, respectively. Studies have been conducted to see if the conversion of glutamate and NADH to P5C and NAD+ is catalyzed by this enzyme. These studies have established that if the reverse reaction occurs the rate is 1/15,000th of the rate at which P5C is oxidized to glutamate. The concentration of the substrates needed in the assay results in a high background that interferes with accurate spectrophotometric analysis of the rate of NADH production; therefore a radiochemical (2) or a new colorimetric (3) assay was used here. A number of aldehydes were tested as substrates. It was found that the rat and human enzymes (4) have similar requirements for an aldehyde to be a substrate. Both of these proteins interacted with a polyclonal rabbit anti-rat P5C dehydrogenase serum.

1-Pyrroline-5-Carboxylate Dehydrogenase↗