PubMed Health⌕ Search

Biomedical subjects

J W Sparks

Publications and source records attributed to J W Sparks.

At least 19 recordsLinked to original sources
PubMed1995

Use of extracorporeal membrane oxygenation in the septic neonate.

Extracorporeal membrane oxygenation (ECMO) is widely used for cardiopulmonary support in neonates with cardiopulmonary failure secondary to overwhelming sepsis. The purpose of this study was to examine the effects of culture status on the eventual outcome of septic neonates requiring ECMO support. Data from the Extracorporeal Life Support Organization (ELSO) for the tears 1990 through 1992 inclusive were collected and analyzed for all neonates with a primary diagnosis of sepsis. Records were reviewed for gestational age, birth weight, culture status and isolated organism, last arterial blood gas before beginning ECMO, hemorrhagic complications during bypass, and overall survival. Gram-positive sepsis accounted for 85% of positive cultures. Group B streptococcus (GBS) and Escherichia coli were the most commonly isolated organisms (GBS: 95% of all gram-positive sepsis; E coli: 76% of all gram-negative sepsis) from culture-positive patients. Culture-negative patients were found to have a significantly lower mortality rate compared with culture positive patients (16.6% versus 26.9%, P < .001). The incidence of intracranial hemorrhage (ICH) was greater in culture-positive neonates when compared with culture negative (27.6% versus 20.1%, P < .05). There was no difference in the incidence of ICH or eventual outcome between gram-positive and gram-negative sepsis. The culture-positive, septic neonate who requires ECMO support appears to be at an increased risk for intracranial hemorrhage and death. Intracranial hemorrhage appears to be the primary factor affecting survival in these patients. The etiologic organism does not affect the incidence of ICH or outcome. Frequent head ultrasounds and strict control of coagulation parameters are recommended in this patient population.

Cardiac Output, Low↗
PubMed1995

Identification of a unique form of protein C in the ovine fetus: developmentally linked transition to the adult form.

To investigate fetal development of protein C, a pregnant ovine model was used. Protein C was isolated from ovine plasma, and a polyclonal antibody was raised. Citrated plasma was obtained from undisturbed chronically catheterized fetal lambs. On Western blot, nonreduced adult ovine protein C had a molecular mass of 70 kD. Fetal ovine protein C was determined to have a molecular mass of 4 to 6 kD larger than the adult molecule. Crossed immunoelectrophoresis demonstrated slightly increased anodal migration of the fetal form. Isoelectric focusing demonstrated a decreased pI of the fetal molecule (4.45 versus 4.6). The ovine protein C molecules were deglycosylated with N-glycanase. Deglycosylated fetal protein C migrated more similarly to the adult form, although a portion of the fetal form persisted. These experiments demonstrate the first example of a unique fetal form of a vitamin K-dependent protein and are compatible with increased glycosylation of fetal ovine protein C. It is speculated that altered posttranslational processing may exist as a general process by which certain coagulation proteins are modified during fetal development. mRNA was isolated from maternal and fetal hepatic tissue and analyzed by Northern hybridization. Fetal plasma concentration and hepatic mRNA for protein C were both 40% of normal maternal values from midgestation onward. At term, protein C mRNA increased to adult range (p < 0.025), although plasma protein C concentration decreased slightly (p < 0.001). A transition from fetal to adult protein C form was found beginning 6 d before term birth, with a doubling time of 24 h. These data are compatible with a gestationally determined maturation of ovine protein C.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1992

Renal insufficiency secondary to 2,8-dihydroxyadenine urolithiasis.

A 48-year-old man with a history of recurrent urolithiasis and chronic renal failure underwent a nephrectomy for a renal mass. At surgery the mass proved to be a calculus impacted in a dilated calyx. Gross examination of the kidney revealed chalky white deposits in the deep medulla and papillary tips. Histologic examination revealed chronic interstitial nephritis with brown spicules within some tubular epithelial cells and larger deposits of brown crystals within tubular lumina, the interstitium of the medulla, and papillary tips. Polarization microscopy revealed individual crystals scattered throughout the renal parenchyma. Although the arrangement of the crystals was reminiscent of uric acid, and, in fact, a clinical diagnosis of gouty nephropathy was made, x-ray diffraction analysis demonstrated crystals of 2,8-dihydroxyadenine. Enzymatic studies confirmed the complete absence of adenine phosphoribosyltransferase activity in erythrocyte lysates.

Adenine↗
PubMed1992

Hepatic metabolism of glucose, galactose, and lactate after milk feeding in newborn lambs.

The purpose of this study was to test the ability of the liver to efficiently clear substrates absorbed from the gastrointestinal tract after a feeding before entry into the systemic circulation. We placed a hepatic vein (HV) catheter in utero at 135-140 days gestation. The lamb was then allowed to deliver spontaneously, and additional catheters were placed in the portal vein (PV) and femoral artery (FA) at 1-3 days postnatal age. After at least 2 days recovery, lambs were fasted overnight at 4-10 days of age and then allowed to nurse ad libitum. There was significant hepatic glucose release during fasting and after 80 min postprandially. No net hepatic uptake of glucose was observed before or after feeding. PV galactose was significantly greater than FA and HV from 40 to 160 min after feeding (P less than 0.005). Hepatic glucose extraction was negligible in the fasted state (1 +/- 3%) and increased after feeding to 75 +/- 2% when PV galactose was less than 1.0 mM. There was a significant hepatic arteriovenous concentration difference of lactate (0.23 +/- 0.03 mM) and of oxygen (0.27 +/- 0.01 mM), which did not change significantly after feeding. The metabolic quotient for galactose increased significantly after feeding, such that galactose was the largest carbon contributor for postprandial hepatic carbon accretion. After a milk feeding, the newborn liver efficiently extracts galactose, lactate, and oxygen, but not glucose.

Animals↗
PubMed1992

Fetal serine fluxes across fetal liver, hindlimb, and placenta in late gestation.

Eleven studies of fetal serine fluxes were performed in chronically catheterized fetal lambs by continuous infusion of [1-13C]- and [U-14C]serine into a fetal brachial vein. At tracer serine steady state, samples were collected from the fetal abdominal aorta, umbilical vein, fetal hepatic vein, and fetal femoral vein and from the maternal femoral artery and uterine vein. Analyses were performed for plasma serine and glycine concentration, for serine and glycine 13C mole percent enrichment, and for whole blood 14CO2 and O2 concentrations. Uterine and umbilical blood flows were also measured. The placenta had a significant net uptake of fetal serine (2.1 +/- 0.5 mumol.min-1.kg-1, P < 0.01). Fetal plasma serine disposal rate (DR) was 42.5 +/- 3.9 mumol.min-1.kg-1.CO2 production from decarboxylation of fetal plasma serine represented 7.9 +/- 0.5% of DR, or 10.1 +/- 1.2 mumol CO2.min-1.kg-1. Fetal plasma glycine enrichment was 59.7 +/- 4.9% of fetal plasma serine enrichment. There was a significant loss of tracer serine from the fetal circulation into the placenta accounting for approximately 45% of infused tracer. Fifteen percent of this was converted to glycine and released into the umbilical circulation. There was a significant uptake of tracer serine by both fetal liver and fetal hindlimb with a significant CO2 production by both sites with serine oxidation predominantly in the carcass. These results indicate a high fetal serine disposal rate in the lamb, with rapid fetoplacental serine exchange, resulting in a net uptake of fetal serine by the placenta.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Glycine turnover and oxidation and hepatic serine synthesis from glycine in fetal lambs.

[1-13C]- and [1-14C]glycine were infused into chronically catheterized fetal lambs via a brachial vein. At tracer glycine steady state, samples were collected from the fetal abdominal aorta, umbilical vein, and fetal hepatic vein and from the maternal femoral artery and uterine vein. The samples were analyzed for plasma glycine and serine, for glycine and serine 13C atom% excess (APE), and for whole blood 14CO2 and O2 concentrations. Fetal plasma glycine disposal rate (DR) was 12.4 +/- 0.8 mumol.min-1.kg fetus-1.CO2 production from decarboxylation of fetal plasma glycine was 1.63 +/- 0.16 mumol.min-1.kg fetus-1 and represented 12.3 +/- 0.7% of DR. Approximately 50% of infused tracer glycine was taken up by the fetal liver with the release of labeled serine and CO2 in the fetal circulation. There was no detectable efflux of tracer glycine from the placenta into the maternal circulation. The tracer production of serine and CO2 accounted for 23 and 17%, respectively, of the hepatic tracer glycine uptake. The labeled CO2 released by the liver was a large fraction (approximately 70%) of the labeled CO2 produced by the fetus. The serine-to-glycine APE ratio in fetal plasma was approximately 5%. These results indicate that the fetal liver is the major site of fetal plasma glycine decarboxylation and of serine synthesis from plasma glycine.

Animals↗
PubMed1991

Role of the circulation in measurement of lactate turnover rate.

Previous studies have shown that venous lactate specific activity during arterial tracer lactate infusion differs from arterial lactate specific activity during systemic venous tracer lactate infusion. We performed paired experiments on chronically catheterized rabbits to compare left ventricular (LV) infusion with femoral venous (FV) infusion of L-[U-14C]lactate. Blood was sampled from both the femoral artery (FA) and right ventricle (RV) during both modes of infusion. The mean lactate specific activity measured for each combination (infusion site, sampling site) was (FV,FA) 4,380 +/- 452, (FV,RV) 4,370 +/- 471, (LV,FA) 4,364 +/- 239, and (LV,RV) 3,325 +/- 240 (SE) dpm/mumol. Lactate turnover calculated from the specific activity in the (LV,RV) mode was significantly higher than from the other three modes (P less than 0.001). Models of lactate turnover are discussed demonstrating that the (FV,FA) and analogous modes of infusion sampling measure the turnover rate of lactate molecules that cycle through the circulation. This estimate of turnover is less than the turnover rate by the whole organism to the extent that some produced lactate is metabolized locally without entering the general circulation. The turnover calculated by the (LV,RV) mode overestimates the turnover of circulating lactate and relates to whole body lactate turnover in a complex manner.

Animals↗
PubMed1990

Galactose clearance and carbohydrate metabolism across the gastrointestinal tract in the newborn lamb.

We prepared 16 newborn lambs with chronically indwelling catheters in the portal vein, mesenteric vein, femoral vein, and femoral artery to study galactose clearance, portal venous blood flow, and carbohydrate metabolism across the gastrointestinal (GI) tract. Galactose clearance was measured by infusing galactose into the femoral vein to achieve a steady-state galactose concentration in the femoral artery. We observed a curvilinear relationship between galactose clearance and the steady-state galactose concentration. The relationship could be modeled as an apparent Michaelis-Menten system: Clearance = Vmax/(Km + [Gal]ssa), where Vmax = 17.0 +/- 2.5 mg/min/kg body weight and Km = 11.0 +/- 0.4 mg/dL. Substrate/oxygen quotients across the viscera drained by the portal vein were measured in the fasted state and during systemic galactose infusion. A net uptake of glucose and galactose by the GI tract was found with quotients of 0.19 +/- 0.07 and 0.05 +/- 0.02, respectively. There was a relatively large net efflux of lactate across the portal circulation, with a quotient of -0.13 +/- 0.03. The indicator-dilution technique was used to estimate portal venous blood flow (PVBF) in the neonatal period with a resting, fasted state value of 92.8 +/- 4.4 mL/min/kg body weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Clinical application of a new glucose analyzer in the neonatal intensive care unit: comparison with other methods.

We evaluated the operation of the Yellow Springs Instrument Co. (YSI) glucose analyzer (model 23A) by clinical nurses for the measurement of blood glucose in the intensive care nursery. In vitro performance was determined with the use of aqueous standards; with a 2-point calibration of 0.0 and 200 mg/dl, a precision of better than 1.0% of each standard (25, 50, 100, 200 mg/dl) was achieved, and the linearity was excellent (Y = 0.99X - 0.49, r = 0.99). The YSI correlated well with a manual spectrophotometric glucose oxidase method (r = 0.99) and the Kodak Ektachem analyzer (r = 0.98) using human umbilical cord blood samples. Five trained clinical nurses performed all YSI and glucose reagent strip analyses, including all in vitro and patient samples. Four reagent strip methods were compared with the YSI from 104 neonatal heel-stick blood samples: Glucometer II with memory (r = 0.73), Glucostix (r = 0.74), Dextrostix (r = 0.70), and Chemstrip bG (r = 0.83). We conclude that clinical nurses can and do learn to use the YSI with excellent precision and that the YSI represents an improved method for measuring glucose concentrations in the newborn intensive care nursery.

Blood Chemical Analysis↗
PubMed1989

A comparison of amino acid arteriovenous differences across the liver and placenta of the fetal lamb.

Amino acid and ammonia concentrations as well as oxygen content were measured in either the right or left hepatic vein, the umbilical vein, and the umbilical artery in 13 fetal lambs in late gestation. There was an uptake of all of the essential and most of the nonessential amino acids by both lobes of the fetal liver. The umbilical venous-hepatic venous amino acid concentration differences were similar in the two hepatic lobes. While glutamine and glycine were taken up by both hepatic lobes, their metabolically related amino acids, glutamate and serine, were released by the fetal liver into the systemic circulation. There was a reciprocal net placental uptake from the umbilical circulation of glutamate and serine and a net fetal of glutamine and glycine, suggestive of interorgan cycling of these amino acids between the placenta and fetal liver. Total fetal umbilical nitrogen uptake was 0.91 g N.kg-1.day-1. The umbilical venous-hepatic venous differences of ammonia were positive and not significantly different in the two lobes. There was a significant umbilical uptake of ammonia (12.8 +/- 1.8 microM; 0.0078 microM NH3/microM O2). However, 0 the ratios of NH3 to O2 were much higher in each lobe (right, 0.060; left, 0.079; each P less than 0.01) than in the umbilical circulation.

Amino Acids↗
PubMed1988

Patterns of serum glucose and galactose concentrations in term newborn infants after milk feeding.

Galactose and glucose concentrations were measured in peripheral blood in relation to ad libitum milk feeding in 11 healthy near-term infants. Galactose and glucose concentrations before feeding averaged 1.06 +/- 0.21 and 60.3 +/- 3.2 mg/dl, respectively. After feedings containing 0.76-2.68 g lactose/kg body weight, both galactose and glucose rose by approximately 35% Galactose concentrations rose by 0.72 +/- 0.10 mg/dl at 30 min after feeding, while glucose concentration rose by 23.3 +/- 2.5 mg/dl at 30 min after feeding. The 25-fold greater absolute increase in the concentration of glucose than galactose is consistent with efficient first-pass clearance of galactose by the neonatal liver.

Analysis of Variance↗
PubMed1988

Uterine metabolism of the pregnant guinea pig as a function of gestational age.

During the last half of pregnancy, the fetal guinea pig grows exponentially at 7.1%/day. In order to define the metabolic requirements of the gravid uterus during this period of rapid growth, catheters were placed in the femoral artery and uterine vein of guinea pigs at gestational ages ranging from 40 days to term (68 days). The animals were studied in the unstressed state after full recovery from surgery and anesthesia. Arterial and venous concentrations of oxygen, glucose, lactate, acetoacetate, beta-hydroxybutyrate, and acetate were measured, and metabolic quotients and coefficients of extraction were calculated. The glucose/oxygen quotient did not change significantly in the last half of pregnancy averaging 1.26, while the lactate/oxygen quotient remained unchanged at -0.42, and the (glucose + lactate)/oxygen quotient remained unchanged at 0.82. Coefficients of extraction of glucose and oxygen increased linearly with gestational age. The increase in supply of substrates for the rapid growth of the conceptus toward the end of gestation is accounted for by increasing extraction of substrate and by greatly increasing blood flow with increasing gestation. While glucose remains the major metabolic fuel of the guinea pig conceptus and acetate is consistently taken up by the uterus, these substrates alone cannot account for the metabolic fate of the oxygen taken up and fall far short of the predicted nutritional requirements of the fetus for both oxidative metabolism and growth.

3-Hydroxybutyric Acid↗
PubMed1988

Galactose, glucose, and lactate concentrations in the portal venous and arterial circulations of newborn lambs after nursing.

We have used the newborn lamb prepared with chronic indwelling catheters to study carbohydrate metabolism in the unstressed, postprandial state. Lambs were fasted 5 h and then allowed to nurse ad libitum from their mothers for 20 min. Serial determinations of whole blood galactose, glucose, and lactate concentration were then made from the portal venous and arterial circulations. Portal venous galactose concentration increased significantly after milk ingestion, but arterial galactose concentration did not increase from baseline unless the portal venous galactose concentration exceeded 10-12 mg/dl suggesting a threshold effect for hepatic galactose clearance. Glucose concentration increased significantly in both circulations with portal venous galactose concentration greater than arterial galactose concentration in all cases. Galactose and glucose were absorbed from the intestine at approximately equal rates. Lactate was not absorbed into the portal venous circulation to any great extent after lactose ingestion.

Animals↗
PubMed1987

Fructose disposal and oxidation rates in the ovine fetus.

Fructose disposal and oxidation rates were measured in fetal lambs receiving a constant intravenous infusion of D-[U-14C]fructose. Approximately 60% of the infused tracer entered the placenta, but loss of fructose into the maternal circulation was negligible. Fructose was metabolized to lactate and CO2 in both the placenta and fetus, whereas there was no detectable conversion to glucose. In well-fed ewes the fetal disposal and utilization rates of fructose were 2.4 +/- 0.17 and 0.97 +/- 0.09 mg/min. kg, respectively. The umbilical excretion rate of CO2 originating from the oxidation of fetal fructose was 18.1 +/- 1.3 mumol/min. kg or 5.3% of total fetal CO2 production. This excretion rate is one-fifth of the CO2 excretion rate from fetal glucose carbon. In four ewes comparison of fructose metabolism in the fed and fasted states showed a significant decrease of fructose production and oxidation with fasting. Although fructose is present in high concentrations in the fetal blood of ungulates, its contribution to fetal oxidative metabolism is relatively small in comparison to glucose.

Animals↗
PubMed1986

Molecular basis for substrate specificity of protein kinases and phosphatases.

Regulation of various metabolic processes occurs by the phosphorylation/dephosphorylation of enzymes. Both the protein kinases that catalyze the phosphorylations and the protein phosphatases that catalyze the dephosphorylations display relatively broad specificity, reacting with a number of distinct sites in target enzymes. In this way changes in the activity of a particular kinase or phosphatase can cause coordinated and pleiotropic responses. However, the kinases and phosphatases do not exhibit a one-to-one correspondence in their reactions. Residues at different positions may be phosphorylated by a single kinase, yet dephosphorylated by different individual phosphatases. Conversely, sites which are substrates for different individual kinases may be dephosphorylated by a single phosphatase. In exploring the molecular basis for these differences this article shows that whereas kinases react with specific primary structures that often times appear as beta bends, the phosphatases recognize higher order structure, less strictly ruled by amino acid sequence surrounding the phosphorylated site. The differences, seen in the ability of these enzymes to utilize synthetic peptide substrates, might be rationalized in terms of function. Kinases need protruding segments of structure that can be enwrapped to exclude water, thereby minimizing ATP hydrolysis and enhancing phosphotransferase activity. On the other hand phosphatases are hydrolytic enzymes that may operate especially well on protein interfaces. Hydrolytic action often measured with p-nitrophenylphosphate is not necessarily indicative of a protein phosphatase and consideration of the mechanism reveals why this substrate can be misleading.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Nitrophenylphosphatase↗
PubMed1986

Factors affecting radioactive microsphere measurement of blood flow in pregnant guinea pigs.

Comparative blood flow studies were performed in pregnant guinea pigs using radioactive microspheres to test the effects of different sphere sizes on blood flow measurements and the relationship between flows obtained intraoperatively and those performed after 5 days of recovery from anesthesia and surgery. We observed that 1.5% of the cardiac output was shunted through the microcirculation of the carcass, gut, skin and endomyometrium when 15 mu microspheres were used. Intraoperative measurements of heart rate, cardiac output and placental blood flow are significantly lower than measurements made after 5 days recovery. These reductions were ameliorated with the addition of a continuous infusion of isoproterenol and the deletion of atropine from the anesthetic.

Animals↗
PubMed1985

Specificity of protein phosphotyrosine phosphatases. Comparison with mammalian alkaline phosphatase using polypeptide substrates.

The specificity of cytosolic protein phosphotyrosine (PPT) phosphatases was investigated using different peptides and proteins that were phosphorylated on tyrosine residues by the EGF receptor kinase. The acidic phosphoproteins, serum albumin, casein, and myosin light chains, were dephosphorylated by the PPT phosphatases with apparent Km values of 1.2 to 12.5 microM and apparent velocities of 0.2 to 18 mumol/min/mg. In contrast, [Tyr(32P)]histone and the phosphotyrosine peptides [Val5]angiotensin and RR-src, a peptide with sequence Arg-Arg-Leu-Ile-Glu-Asp-Ala-Glu-Tyr-Ala-Ala-Arg-Gly, were unreactive with the PPT phosphatases. However, each of these unreactive phosphopolypeptides was dephosphorylated under the same conditions by calf-intestine alkaline phosphatase. The data reveal how PPT phosphatase activity has been ascribed to different cellular enzymes. When acidic phosphotyrosine proteins were used as substrates in assays for PPT phosphatase activity the cytosolic enzymes were isolated, whereas when phosphotyrosine histones were used as substrates only the membrane-bound alkaline phosphatase was detected. Apparently the protein tyrosine kinase and the protein tyrosine phosphatases do not have the same specificity, so substrates such as histone, angiotensin, or RR-src are phosphorylated but not hydrolyzed. Therefore, these polypeptides would be ideal for the characterization of protein tyrosine kinases in cellular extracts.

Alkaline Phosphatase↗