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D W Pearson

Publications and source records attributed to D W Pearson.

At least 19 recordsLinked to original sources
PubMed1992

The ranges of insulin response and glucose tolerance in lean, normal, and obese women during pregnancy.

OBJECTIVE: We characterized insulin secretion and glucose disposal in a large unselected group of women, encompassing the full spectrum of glucose tolerance in pregnancy, and related the findings to maternal obesity. STUDY DESIGN: Intravenous glucose tolerance and first-phase insulin response were measured at about 32 weeks' gestation in 690 unselected pregnancies. The women were designated as "lean," "normal," or "obese" on weight-for-height criteria. RESULTS: The distribution of insulin response was bimodal, but there was no corresponding dichotomy in maternal glucose disposal rate. Insulin response was greatest and glucose disposal rate slowest in obese women. In general, "poor" glucose tolerance was associated with relatively low insulin output. It was not possible to identify any cluster of women, obese or otherwise, in whom poor glucose tolerance was specifically associated with an unusually high insulin response. CONCLUSION: The data indicate that the distribution of glucose tolerance in pregnancy is a continuum. Glucose intolerance represents one end of that spectrum and is attributable to insufficient insulin secretion. This relative insufficiency is most frequent with maternal obesity.

Blood Glucose↗
PubMed1991

Synchrotron-produced ultrasoft X-rays: a tool for testing biophysical models of radiation action.

Ultrasoft X-rays are useful for mechanistic studies of ionizing radiation damage in living cells due to the localized nature of their energy depositions. To date radiobiology experiments in this energy region have relied on characteristic X-rays (mainly Alk and Ck) from X-ray tubes. However, limitations in the photon intensity and the available energies from X-ray tube sources prevent a definitive characterization of the relationship between photon energy and biological damage. Synchrotron radiation has the potential to avoid these limitations, since it produces X-rays with high intensity over a continuous spectrum. We have established a synchrotron-based system for radiation biology studies using the ES-0 exposure station of the Center for X-ray Lithography at the University of Wisconsin Synchrotron Radiation Center storage ring, Aladdin. A characterization of the system including spectral and intensity properties of the photon beam is presented. The first mammalian cell survival curve for synchrotron-produced ultrasoft X-rays was generated and is presented. Cell survival curves of C3H/10T 1/2 cells using synchrotron radiation of 1.48 keV agree with previous data using Alk X-rays (1.49 keV). An RBE of 1.47 +/- 0.30 at the 10% survival level was measured with reference to 250 kVp X-rays.

Animals↗
PubMed1991

Neutrophil nicotinamide adenine dinucleotide phosphate oxidase assembly. Translocation of p47-phox and p67-phox requires interaction between p47-phox and cytochrome b558.

Two of the cytosolic NADPH oxidase components, p47-phox and p67-phox, translocate to the plasma membrane in normal neutrophils stimulated with phorbol myristate acetate (PMA). We have now studied the translocation process in neutrophils of patients with chronic granulomatous disease (CGD), an inherited syndrome in which the oxidase system fails to produce superoxide due to lesions affecting any one of its four known components: the gp91-phox and p22-phox subunits of cytochrome b558 (the membrane-bound terminal electron transporter of the oxidase), p47-phox, and p67-phox. In contrast to normal cells, neither p47-phox nor p67-phox translocated to the membrane in PMA-stimulated CGD neutrophils which lack cytochrome b558. In one patient with a rare X-linked form of CGD caused by a Pro----His substitution in gp91-phox, but whose neutrophils have normal levels of this mutant cytochrome b558, translocation was normal. In two patients with p47-phox deficiency, p67-phox failed to translocate, whereas p47-phox was detected in the particulate fraction of PMA-stimulated neutrophils from two patients deficient in p67-phox. Our data suggest that cytochrome b558 or a closely linked factor provides an essential membrane docking site for the cytosolic oxidase components and that it is p47-phox that mediates the assembly of these components on the membrane.

Biological Transport↗
PubMed1991

A simple approach to screening for microalbuminuria in a type 1 (insulin-dependent) diabetic population.

The reproducibility of albumin concentration in first-morning samples of urine was assessed in 334 insulin-dependent diabetic patients aged 18-60 years. The albumin excretion rate was determined immunoturbidimetrically in three sterile, Albustix-negative, first-morning urine samples submitted over a week. An abnormally high mean value, greater than or equal to 2.5 mg albumin per mmol creatinine (Ua/Uc), was found in 33 patients (9.9%). These patients were older (mean 42 vs 34 years, P less than 0.01), had longer disease duration (18 vs 14 years, P less than 0.01) and higher HbA1c values (6.8 vs 6.3%, P less than 0.05) than those without microalbuminuria. Although triplicate samples were collected within 7 days, Ua/Uc showed considerable intraindividual variation, with a mean coefficient of variation of 49%. Despite this it was found that Ua/Uc values greater than 1 mg/mmol on the first specimen had a sensitivity of 97% and a specificity of 82% for detecting those with a three-sample mean value greater than 2.5 mg/mmol. Thus virtually all those with microalbuminuria (32/33) had a single first-morning result greater than 1 mg/mmol, and in those with a lower ratio microalbuminuria was excluded with more than 99% certainty.

Adolescent↗
PubMed1990

Insulin management during labour and delivery in mothers with diabetes.

A standardized intravenous regimen has been assessed, in 25 insulin-treated diabetic women, for insulin and dextrose therapy in labour and delivery. Adjustments to insulin infusion rate are determined by trends in blood glucose as well as by absolute concentration, in order to approach normoglycaemia. Blood glucose was 5.0 (SD 1.7) mmol l-1 on arrival in labour (or at 0800 h before planned delivery) and was maintained at 6.0 (SD 1.8) mmol l-1 with insulin 0-5 U h-1 for up to 29 h before delivery, when it was 6.3 (SD 2.1, range 3.0-9.0) mmol l-1 with insulin infusion rate 0-4 U h-1. Neonatal blood glucose (less than 2.0 mmol l-1 in 11 babies) correlated with both maternal HbA1c (rs = -0.47, p less than 0.02) and maternal blood glucose at delivery (rs = -0.58, p less than 0.01). During 12 months observation on the intravenous regimen, 339 measurements of blood glucose were made; 10 were less than 3.0 mmol l-1, 242 were 3.0-8.0 mmol l-1, and 81 were greater than 8.0 mmol l-1 (mean 6.5, range 2.7-13.5 mmol l-1). Insulin infusion rate ranged from 0 to 5 U h-1, with 139 rate adjustments. Only one mild clinical hypoglycaemic episode, responding to increased dextrose infusion, was recorded. This simple flexible regimen proved clinically reliable for both midwifery and medical staff.

Cesarean Section↗
PubMed1990

A comparison between the diets of pregnant diabetic women and pregnant non-diabetic women.

In order to assess the effect of dietary advice for pregnant diabetic women, the habitual dietary intake of 8 pregnant diabetic women was assessed by 7-day weighed food records. These results were compared with records from 8 non-diabetic women, matched for age and gestation. Despite intense personalized dietetic advice to the diabetic women, there were no statistically significant differences in macro-nutrient intake between the two groups. The diabetic women were encouraged to increase their carbohydrate intake slightly, but failed to achieve current British Diabetic Association dietary recommendations with respect to percent energy from carbohydrate (41 +/- 5 (+/- SE)(range 29-47)%, BDA recommendation greater than 50%) and percentage from fat 43 +/- 6 (33-51)%, BDA recommendation less than 30%). Intake of bread and cereals was increased in the diabetic women, but increases in complex carbohydrates were insufficient to compensate for a reduced intake of high-sugar foods. Intakes of energy from simple sugars were significantly lower (p less than 0.05) in the diabetic group (12 +/- 2 (5-20)%) than in the non-diabetic group (21 +/- 2 (12-28)%). There was no detectable difference in sources of fats in the diet between the two groups.

Adult↗
PubMed1989

Genetic variants of chronic granulomatous disease: prevalence of deficiencies of two cytosolic components of the NADPH oxidase system.

Chronic granulomatous disease, a syndrome of recurrent infections and failure of oxidative microbicidal activity in phagocytes, results from defects in the gene for one of several components of an oxidase system that can undergo activation. To determine the relative prevalence of certain of the genetic variants of this disorder, we used immunoblotting to detect two specific neutrophil cytosolic proteins of 47 and 67 kd recently shown to be required for oxidase activation. Chronic granulomatous disease is usually an X-linked disorder associated with the absence of membrane cytochrome b558. Of our 94 patients with chronic granulomatous disease, however, 36 had a phenotype characterized by autosomal inheritance, normal membrane oxidase components (including cytochrome b558), and functionally defective cytosolic activity in a cell-free oxidase system. We studied 25 of these 36 patients and found that 22 lacked the 47-kd cytosolic protein, and the remaining 3 were missing the 67-kd component. Patients with chronic granulomatous disease whose functional defect was localized to the neutrophil membrane (classic X-linked cytochrome b-negative type and two other rare variants) had normal amounts of both cytosolic components. We estimate that approximately 33 percent of all patients with chronic granulomatous disease are missing the 47-kd cytosolic oxidase component and about 5 percent of patients are missing the 67-kd component. Chronic granulomatous disease caused by a defect in any cytosolic factors other than the 47-kd and 67-kd proteins, if it exists, is apparently rare.

Adolescent↗
PubMed1989

Inactivation of transferrin iron binding capacity by the neutrophil myeloperoxidase system.

Human serum apotransferrin was exposed to the isolated myeloperoxidase-H2O2-halide system or to phorbol ester-activated human neutrophils. Such treatment resulted in a marked loss in transferrin iron binding capacity as well as concomitant iodination of transferrin. Each component of the cell-free system (myeloperoxidase, H2O2, iodide) or neutrophil system (neutrophils, phorbol ester, iodide) was required in order to observe these changes. In the cell-free system, the H2O2 requirement was fulfilled by either reagent H2O2 or the peroxide-generating system glucose oxidase plus glucose. Both loss of iron binding capacity and transferrin iodination by either the myeloperoxidase system or activated neutrophils were blocked by azide or catalase. The isolated peroxidase system had an acidic pH optimum, whereas the intact cell system was more efficient at neutral pH. The kinetics of changes in iron binding capacity and iodination closely paralleled one another, exhibiting t1/2 values of less than 1 min for the myeloperoxidase-H2O2 system, 3-4 min for the myeloperoxidase-glucose oxidase system, and 8 min for the neutrophil system. That the occupied binding site is protected from the myeloperoxidase system was suggested by 1) a failure to mobilize iron from iron-loaded transferrin, 2) an inverse correlation between initial iron saturation and myeloperoxidase-mediated loss of iron binding capacity, and 3) decreased myeloperoxidase-mediated iodination of iron-loaded versus apotransferrin. Since as little as 1 atom of iodide bound per molecule of transferrin was associated with substantial losses in iron binding capacity, there appears to be a high specificity of myeloperoxidase-catalyzed iodination for residues at or near the iron binding sites. Amino acid analysis of iodinated transferrin (approximately 2 atoms/molecule) demonstrated that iodotyrosine was the predominant iodinated species. These observations document the ability of neutrophils to inactivate transferrin iron binding capacity via the secretion of myeloperoxidase, formation of H2O2, and subsequent myeloperoxidase-catalyzed iodination. This sequence of events may help to explain the changes in iron metabolism associated with the in vivo inflammatory response.

Amino Acids↗
PubMed1988

The influence of maternal glucose metabolism on fetal growth, development and morbidity in 917 singleton pregnancies in nondiabetic women.

To study the effects on the fetus of variations in maternal glucose tolerance, a 25 g rapid intravenous glucose tolerance test was performed at or about 32 weeks gestation in 917 randomly selected nondiabetic women with singleton pregnancies. The results were withheld from the patients and their obstetricians and paediatricians, and no treatment or advice was offered. Fasting plasma glucose and indices of glucose disposal (including a new index which we have termed "summed glucose") were distributed unimodally, with no evidence of a separate pathological group towards the diabetic end of the distributions. Significant associations were found between maternal glucose metabolism and various measures of neonatal nutrition and morbidity, including the incidence of congenital malformations and morbidity related to asphyxia, suggesting that variations within the normal range in maternal glucose metabolism can influence growth and development in the fetus. These relationships were continuous throughout the range of maternal glucose tolerance and were not of predictive value in individual cases.

Birth Weight↗
PubMed1988

Management of the pregnant diabetic patient.

The prognosis in diabetic pregnancy has greatly improved as a result of patient education and the availability of home blood glucose monitoring techniques enabling the implementation of good metabolic control pre-pregnancy, antenatal and intrapartum. These in turn have made possible the benefits to the offspring of vaginal delivery at term. Screening for gestational diabetes is important and the prognosis is also good where maternal normoglycaemia is achieved. All diabetic pregnancies should be cared for in specialist units under the supervision of an integrated team comprising an obstetrician, diabetologist and paediatrician, and for optimal results care should start prior to conception.

Female↗
PubMed1987

NADPH oxidase of human neutrophils. Subcellular localization and characterization of an arachidonate-activatable superoxide-generating system.

The superoxide-forming NADPH oxidase of human neutrophils was studied in subcellular fractions of unstimulated cells. Purified neutrophils were disrupted by nitrogen cavitation and separated on Percoll density gradients into four fractions: alpha, azurophil granules; beta, mostly specific granules; gamma, plasma membrane, and cytosol. NADPH-dependent O2-. formation by these fractions was quantitated as the rate of superoxide dismutase-inhibitable reduction of ferricytochrome c. In the presence of cytosol, NADPH, and either arachidonic acid (optimum 90 microM) or sodium dodecyl sulfate (optimum 160 microM), 70-75% of the oxidase was in the beta fraction and about 25% was in the gamma fraction. A similar distribution was found for cytochrome b559 and FAD, two putative components of the oxidase. The reaction rates observed with arachidonic acid activation were sufficient to account for 25-75% of the O2-. generated by intact neutrophils. The properties of the beta and gamma enzymes were similar and closely resembled those of the oxidase in intact neutrophils or disrupted prestimulated cells. These included resistance to azide and cyanide, a pH optimum of 7.4, and a preference for NADPH (Km approximately 40-45 microM) rather than NADH (Km approximately 2.5 mM) as the electron donor. The combination of beta and gamma fractions displayed additive activity. The activatable oxidase required Mg2+ but not Ca2+. ATP was required for maximum reaction rates. When beta and gamma membranes were preincubated with cytosol and arachidonic acid in the presence of millimolar Mg2+ and then ultracentrifuged membrane-bound O2-. -forming activity was recovered in the pellet and the enzyme required only NADPH (i.e. no cytosol, arachidonic acid, or Mg2+) for expression of activity. These data suggest that cytosol contains a Mg2+-dependent oxidase-activating factor. Molecular sieve chromatography of cytosol indicated a single peak of activity (i.e. ability to activate O2-. generation by beta and/or gamma fraction) eluting with molecules of about 10,000 daltons.

Arachidonic Acid↗
PubMed1987

An in vivo technique for the measurement of bone blood flow in animals.

A new technique to measure the in vivo clearance of 41Ar from the bone mineral matrix is demonstrated following fast neutron production of 41Ar in bone via the 44Ca(n, alpha) reaction at 14.1 MeV. At the end of irradiation, the 41Ar activity is assayed with a Ge(Li) detector where sequential gamma-ray spectra are taken. Following full-energy peak integration, background and dead time correction, the activity of 41Ar as a function of time is determined. Results indicated that the Ar washout from bone in rats using this technique was approximately 16 ml (100 ml min)-1 and in agreement with other measurement techniques. For sheep the bone perfusion in the tibia was approximately 1.9 +/- 0.2 ml (100 ml min)-1.

Animals↗
PubMed1986

The ability of the serum thyrotrophin receptor antibody (TRAb) index and HLA status to predict long-term remission of thyrotoxicosis following medical therapy for Graves' disease.

In agreement with previous authors we found patients with Graves' disease to have an increased incidence of the DR 3 antigen. We could find no association, however, between the presence of the antigen and relapse after carbimazole treatment. A concordant HLA status and thyrotrophin receptor antibody (TRAb) index, obtained at either 6 or 12 months after the start of treatment could only predict cases of relapse and remission in a minority of patients making this of very limited clinical use. The TRAb index obtained at 12 months after the start of medical therapy could accurately predict cases of relapse and remission for the next 3 years in 24/30 patients studied.

Adult↗
PubMed1985

Selenium deficiency in cultured adrenocortical cells: restoration of glutathione peroxidase and resistance to hydroperoxides on addition of selenium.

Cultured bovine adrenocortical cells were previously shown to be functionally deficient in selenium and vitamin E when grown in medium supplemented with fetal bovine serum. In the present experiments, the lack of significant bioavailable amounts of selenium in the medium was demonstrated by the finding of only low levels of glutathione peroxidase in the cultured cells (0.008 U/mg protein compared with 0.045 U/mg protein in fresh adrenocortical tissue). When 20 nM selenium as selenite was added to the cultured adrenocortical cells, glutathione peroxidase activity increased continuously over 72 h, with a total increase of about eightfold over this period. Over the same time-course, the highest concentration of cumene hydroperoxide tolerated by the cells without cell death increased progressively from 10 microM to 50 microM. Addition of 1 microM alpha-tocopherol also increased the amount of cumene hydroperoxide tolerated to 50 microM. Cell death was measured by cloning efficiency after removal of cumene hydroperoxide. Addition of either selenium or alpha-tocopherol had little effect on the growth rate of the cells over six passages, even when residual vitamin E was removed from the serum by extraction with ether and residual low molecular weight selenium compounds were removed by dialysis. It is concluded that combined deficiency of selenium and vitamin E, at least in the presence of other components of fetal bovine serum, has little effect on the ability of the cells to survive under normal conditions, as evidenced by continued long-term proliferation. However, the low levels of glutathione peroxidase resulting from selenium deficiency cause an increase susceptibility to peroxide-mediated toxicity. The combined deficiency of selenium and vitamin E impairs the ability of cells to survive under adverse conditions, as well as altering mitochondrial functions, as previously demonstrated.

Adrenal Cortex↗