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Biomedical subjects

J B Watkins

Publications and source records attributed to J B Watkins.

At least 73 records · Page 4Linked to original sources
PubMed1986

Effect of gestational age upon prealbumin and retinol binding protein in preterm and term infants.

The relationships between maternal and umbilical cord levels of prealbumin and retinol binding protein (RBP) were studied in 68 mothers and in their appropriate-for-gestational-age neonates delivered between 25 and 42 weeks gestation. Arterial and venous concentrations of prealbumin and RBP in cord sera were also studied in a subsample of eight infants. In cord sera, prealbumin and RBP levels increased with gestational age (prealbumin, r = 0.47; RBP, r = 0.40, p less than 0.01), and were significantly different in neonates born at term compared to those born prematurely (mean +/- SD, prealbumin 12.0 +/- 3.9 mg/dl vs. 8.8 +/- 2.3 mg/dl, p less than 0.001; RBP, 2.3 +/- 0.8 vs. 1.8 +/- 0.5 mg/dl, p less than 0.005). No significant differences between arterial and venous concentrations of prealbumin and RBP were observed in cord blood. In maternal blood, serum prealbumin and RBP concentrations did not increase with length of gestation (25-42 weeks). Maternal prealbumin was not correlated significantly with infants' cord serum levels; the correlation coefficient for RBP was 0.29, p less than 0.05. Maternal prealbumin and RBP serum levels were approximately twice the values seen in neonates born both at term and prematurely. Although the difference between premature and full-term cord levels of prealbumin and RBP may reflect an increase in hepatic protein synthesis that occurs with maturation of the fetus and/or a change in placental function after 37 weeks gestation, neither of these factors sufficiently explains the variance in neonatal prealbumin and RBP levels.

Female↗
PubMed1986

Xenobiotic biotransformation in livestock: comparison to other species commonly used in toxicity testing.

Wildlife, domesticated animals and humans are exposed daily to myriad chemicals present in our environment. The risk posed by these chemicals to one species is often determined by extrapolation from data gathered from another species. Several extensive studies have examined the capability of the liver to biotransform xenobiotics in animals commonly used in toxicity testing and in livestock. The present paper is a compilation of these data into a single source to permit comprehensive examination of inter-species variation in rates of hepatic biotransformation. Several substrates were studied for each enzyme system, including cytochrome P-450-dependent monooxygenases, epoxide hydrolases, UDP-glucuronosyltransferases, N-acetyltransferases, glutathione S-transferases and sulfotransferases. The numerous differences in substrate specificity for an individual enzymatic pathway reflect the apparent multiplicity of these enzymes in all 11 species studied. Several hundred- to several thousand-fold differences between species in enzymatic activities for certain substrates under well-defined conditions emphasize the need for caution and the risk of error in extrapolation of xenobiotic metabolism from one species to another. In spite of these uncertainties, knowledge of the rate of biotransformation may help us predict the fate of new chemicals in various species.

Animal Population Groups↗
PubMed1986

Biliary excretion of organic anions in diabetic rats.

Little definitive data are available concerning the effects of insulin deficiency on the hepatic uptake and biliary excretion of endogenous or xenobiotic substances. To expand our understanding of this area, male Sprague-Dawley rats were pretreated with streptozotocin (45 mg/kg i.v.) to induce uncontrolled diabetes. Four to five weeks later, diabetic rats exhibited elevations in serum glucose (640 +/- 13 mg/dl), biliary glucose (307 +/- 35 mg/dl), urine output (166 +/- 11 ml/24 hr), basal bile flow rate (73 +/- 2 microliter/min/kg), liver weight/body weight ratio and bile acid pool size. Polyphagia and generalized muscle atrophy were also evident. Plasma disappearance and biliary excretion of several organic anions were studied after i.v. administration. There were no differences between control and diabetic rats in the plasma elimination and biliary excretion of eosin, phenol-3,6-dibromphthalein disulfonate and sulfobromophthalein. Although hepatic uptake was unchanged, the biliary excretion of amaranth was decreased 30% in diabetic rats. There were no differences in bile flow rate in control or diabetic rats after administration of these four anions. In contrast, administration of indocyanine green, bromcresol green and rose bengal did not depress bile flow in diabetic rats as was observed in control rats. In addition, the rate of maximal biliary excretion was increased by 390, 240 and 151% for rose bengal, indocyanine green and bromcresol green, respectively. Plasma clearance of rose bengal was 65% higher in diabetic rats. Total body clearance and steady-state volume of distribution values for all other anions were not different after induction of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Amaranth Dye↗
PubMed1986

Progression of neurovisceral storage disease with supranuclear ophthalmoplegia following orthotopic liver transplantation.

A 7-year-old girl with progressive ataxia, spasticity, supranuclear ophthalmoplegia, and sea-blue histiocytes in her bone marrow underwent orthotopic liver transplantation for hepatocellular carcinoma. After an initial period of stabilization, she has shown progression of neurologic symptoms with recurrence of storage material in the transplanted liver.

Carcinoma, Hepatocellular↗
PubMed1986

Sphingomyelin lipidosis variant with cirrhosis in the pediatric age group.

Two children with a variant of sphingomyelin lipidosis had otherwise unexplained cirrhosis that was histologically inactive and appeared to run an indolent course. The primary clinical problems involved the central nervous system, with vertical supranuclear ophthalmoplegia being the most distinctive feature. Biochemical analysis of cultured skin fibroblasts obtained from one of the children revealed that sphingomyelinase activity was 42% of control values. The typical inconspicuous hepatic storage and cirrhosis, coupled with the important morphologic finding of sea-blue histiocytes in the marrow, suggested that in cases of unexplained infantile or childhood cirrhosis the marrow should be closely examined for such histiocytes. Likewise, in cases of sea-blue histiocytes without evident etiology, with or without cirrhosis, this disease should be considered.

Adolescent↗
PubMed1985

Intestinal membrane lipid composition and fluidity during development in the rat.

We have characterized microvillus membrane (MVM) lipid composition and derived estimates of membrane fluidity using fluorescence polarization [with 1,6-diphenyl-1,3,5-hexatriene (DPH) as the probe] in MVM from the jejunum and ileum of suckling (day 14-20) and mature postweaning (day 28-49) rats. The anisotropic values are lower (i.e., increased fluidity) in MVM from jejunum and ileum of suckling rats compared with values from MVM of mature rats, suggesting a more disordered molecular environment in MVMs of suckling animals, although the ileal MVM was relatively less fluid than jejunal membranes in both groups. Anisotropic determinations in protein-free MVM liposomes demonstrate that protein-lipid interactions are major determinants of fluidity estimates. Arrhenius plots of DPH anisotropies in MVM and MVM liposomes indicate a thermotropic lipid-phase transition at 23 degrees C in mature rat jejunum and ileum; however, no clear transition point was observed in 14- to 20-day animals. In addition, both the jejunal and ileal MVM in suckling animals contained greater amounts of total lipid, cholesterol, and phospholipid per milligram protein than did mature MVM preparations. Membrane phospholipid composition changed with age, with a decrease in sphingomyelin and an increase in phosphatidylcholine in the jejunum of the postweaning animal and with similar weight ratios of saturated to unsaturated fatty acids in both age groups. The data demonstrate that the small intestinal MVM manifests both age-dependent and regional proximal-distal differences in lipid composition and biophysical properties.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Toxicological effects of gamma-irradiated sewage solids fed as seven percent of diet to sheep for four years.

Breeding ewes in drylot were fed pelleted complete diets with 3% cottonseed meal (CSM) or 7% dried, gamma-irradiated sewage solids (DGSS) for 4 yr. Cytochrome P-450 (P-450) content and enzyme activities for xenobiotics biotransformations were assayed in livers after 2 yr and in livers, kidneys and ileal tissue after 4 yr. Dietary DGSS caused no increase in P-450 and few changes in activities of oxidative, hydrolative and conjugative biotransformational enzymes. Consumption of DGSS for 4 yr caused slight enlargement of spleens (1.1-fold, P less than .10) and ovaries (1.3-fold, P less than .10), but no change in size of livers, kidneys, hearts, adrenals and thyroids (P greater than .10), nor liver vitamin A levels (P greater than .10). Of 22 refractory lipophilic residues assayed in abdominal adipose tissue, few were detected and of those detected DGSS caused none to exceed normal levels. Dietary DGSS increased (P less than .01) Fe in livers 1.5-fold and in spleens 5.6-fold, and increased Cu in livers 1.3-fold (P less than .01) and in kidneys 1.2-fold (P less than .05). Dietary DGSS increased Cd levels in livers (P less than .01) but not in kidneys or spleens (P greater than .10); yet all Cd levels were within ranges for livestock fed conventional feed. Dietary DGSS caused no increase (P greater than .10) in levels of Ag, Ca, Cr, Hg, K, Mg, Mn, Na, Ni, P, Pb or Zn in livers, kidneys or spleens. There were no histopathological lesions of toxicosis except mild hemosiderosis of spleens. Consumption of a diet with 7% DGSS throughout 4 yr caused no hazardous accumulation of toxic elements and little, if any, evidence of toxicosis.

Adipose Tissue↗
PubMed1985

Lipid digestion and absorption.

The importance of nutrient lipids to the developing preterm and term infant has served to focus investigations upon the mechanisms of fat digestion and absorption. The unique physical-chemical properties of the human milk fat globule have been reviewed. Emphasis is placed on the newer understandings that have emerged concerning the intraluminal phase of triglycerides hydrolysis and solubilization of the lipolytic products. The mechanisms of action of the pancreatic lipase, colipase, and phospholipase A2 system, and the importance of intragastric lipolysis for initiating the lipid digestion are explored. Lastly, aspects of bile acid micelle formation and its role on nutrient lipid solubilization and absorption are examined in view of the postnatal adaptations that occur with weaning and the introduction of alternative nutrient sources to the older infant.

Bile Acids and Salts↗
PubMed1984

Long-term assessment of growth, nutritional status, and gastrointestinal function in survivors of necrotizing enterocolitis.

The long-term effect of necrotizing enterocolitis on growth, nutritional status, and gastrointestinal function was assessed in premature infants at the age of 1 year. Of the 22 of 40 infants who developed NEC, 18 were given medical treatment and four required surgical treatment consisting of intestinal resection of less than one fourth of the small bowel. Eighteen infants who did not develop NEC served as controls. At 1 year follow-up, NEC survivors and controls had normal and comparable anthropometric measurements, biochemical values (serum iron, albumin, prealbumin, retinol binding protein, liver function studies) and gastrointestinal tract function (vitamin E absorption, fasting serum bile acids concentration, lactose breath test). This study demonstrates that, in the absence of short bowel syndrome, there is no detectable long-term effect on growth, nutritional status, and gastrointestinal tract function in premature infants who had NEC in the newborn period.

Anthropometry↗
PubMed1984

Oxidative and conjugative metabolism of xenobiotics by livers of cattle, sheep, swine and rats.

Homogenate preparations from fresh livers of cattle, sheep, swine and rats were assayed for microsomal cytochrome P-450 content, for mixed-function oxidase activities and for a wide array of conjugative activities using numerous xenobiotic substrates. Results show that hepatic enzymatic capabilities toward xenobiotics do not parallel phylogenetic classifications, thus strengthening the view that most of the comparative data available at present is more descriptive than predictive of relationships among species. Livestock species differed widely from rats in having lower activities of benzo(alpha)pyrene hydroxylase, glutathione S-transferase and acetyltransferase toward isoniazid and sulfamethazine and UDP-glucuronosyl-transferase toward bilirubin. Acetyltransferase activities toward beta-naphthylamine and 2-aminofluorene were not detected in livers of livestock species studied. Cattle livers were remarkably high in activities of styrene oxide hydrolase, ethoxyresorufin O-deethylase, 2-naphthol sulfotransferase and p-aminobenzoic acid acetyltransferase; but notably low in activity of glutathione-S-transferase toward sulfobromophthalein and 1,2-dichloro-4-nitrobenzene. Swine livers had low activity of glutathione-S-transferase toward four of six substrates and low acetyltransferase activity toward four of five substrates. Sheep livers generally were higher than cattle livers in sulfo- and UDP-glucuronsyltransferase activities and lower in acetyl- and glutathionyl-S-transferase. Findings emphasize the risk of error in extra-polations among species and in extrapolations among substrates.

Acetyltransferases↗
PubMed1984

Effect of diethyl ether on the biliary excretion of acetaminophen.

The biliary and renal excretion of acetaminophen and its metabolites over 8 hr was determined in rats exposed to diethyl ether by inhalation for 1 hr. Additional rats were anesthetized with urethane (1 g/kg ip) while control animals were conscious throughout the experiment (surgery was performed under hexobarbital narcosis: 150 mg/kg ip; 30-min duration). The concentration of UDP-glucuronic acid was decreased 80% in livers from ether-anesthetized rats but was not reduced in urethane-treated animals when compared to that in control rats. The concentration of reduced glutathione was not affected by either urethane or diethyl ether. Basal bile flow was not altered by the anesthetic agents. Bile flow rate after acetaminophen injection (100 mg/kg iv) was increased slightly over basal levels for 2 hr in hexobarbital-treated control rats, was unaltered in urethane-anesthetized animals, and was decreased throughout the 8-hr experiment in rats exposed to diethyl ether for 1 hr. In control and urethane-anesthetized animals, approximately 30-35% of the total acetaminophen dose (100 mg/kg iv) was excreted into bile in 8 hr, while only 16% was excreted in rats anesthetized with diethyl ether. Urinary elimination (60-70% of the dose) was not altered by exposure to ether. Separation of metabolites by reverse-phase high-pressure liquid chromatography showed that ether decreased the biliary elimination of unchanged acetaminophen and its glucuronide, sulfate, and glutathione conjugates by 47, 40, 49, and 73%, respectively, as compared to control rats. Excretion of unchanged acetaminophen and the glutathione conjugate into bile was depressed in urethane-anesthetized animals by 45 and 66%, respectively, whereas elimination of the glucuronide and sulfate conjugates was increased by 27 and 50%, respectively. These results indicate that biliary excretion is influenced by the anesthetic agent and that diethyl ether depresses conjugation with sulfate and glutathione as well as glucuronic acid.

Acetaminophen↗
PubMed1984

Lipid composition and membrane fluidity in the small intestine of the developing rabbit.

Characteristics of small intestinal microvillus membrane lipid composition and associated lipid fluidity were studied throughout postnatal development in the rabbit. Microvillus membranes from jejunal and ileal epithelia were isolated in high purity from 14 days to adulthood. Significant jejunal-ileal differences in microvillus membrane cholesterol to phospholipid molar ratios were observed at all ages. Despite a relatively constant cholesterol content (as percentage of total lipids) both regionally and at all ages, marked increases in the microvillus membrane cholesterol to phospholipid ratio were observed after weaning in both jejunum (14 days = 0.56, adult = 0.83) and ileum (14 days = 0.66, adult = 0.98). Further age-related changes in microvillus membrane lipid composition were characterized by a significant reduction in the weight ratio of saturated to unsaturated fatty acids in jejunum and ileum and by the emergence, in the mature animal, of a jejunal-ileal difference in total lipid content (jejunum = 1.21 mg/mg protein, ileum = 1.01 mg/mg protein). Changes in microvillus membrane lipid fluidity estimated by fluorescence polarization spectrometry directly paralleled changes in the cholesterol to phospholipid molar ratio. Fluorescence anisotropy of jejunal and ileal microvillus membranes increased during the weaning period, suggesting decreased membrane fluidity. At all ages, ileal membranes were relatively less fluid than jejunal microvillus membrane. Studies of protein-free microvillus membrane liposomes, prepared from extracted membrane lipid, confirmed a major lipid-dependent thermotropic transition point at approximately 23 degrees C in adult jejunal and approximately 25 degrees C in adult ileal enterocyte membranes, although no clear transition point was observed in suckling microvillus membrane. These combined data suggested that significant alterations in the microvillus membrane lipid composition and its physical-chemical properties occur during postnatal development in both jejunal and ileal rabbit small intestinal microvillus membrane. It is proposed that membrane lipid-dependent structural characteristics may be directly related to the maturation of enterocyte transport function.

Aging↗
PubMed1983

Hepatic phase I and phase II biotransformations in quail and trout: comparison to other species commonly used in toxicity testing.

The ability of quail and trout to perform a number of representative phase I and phase II biotransformations was examined. To facilitate interspecies comparisons, metabolism of the same substrates was examined simultaneously under uniform conditions for rat, mouse, rabbit, guinea pig, cat, and dog. Both nonmammalian species can metabolize four representative substrates of phase I mixed-function oxidases and one substrate of epoxide hydrolase, though activity tended to be lower than that of the mammals. Important differences in the conjugative pathways were also noted. Among these differences were the quail's relative deficiency in glutathione conjugation and the trout's low ability to conjugate sulfate compounds. Trout liver UDP-glucuronosyltransferase activity was remarkably high toward testosterone and bilirubin, while quail liver formed glucuronides of naphthol, p-nitrophenol, and digitoxigenin-monodigitoxoside. Also noteworthy was the high N-acetyltransferase activity of both quail and trout toward isoniazid, beta-naphthylamine, and 2-aminofluorene. Differences in substrate specificity for a given enzymatic pathway may be an indication that multiple forms of drug metabolizing systems also occur in these nonmammalian species. Observation of several hundred- or even thousand-fold differences between species in their enzyme activities for certain substrates under uniform conditions re-emphasizes the need for caution in extrapolation of xenobiotic metabolism from one species to another.

Acetylation↗
PubMed1983

Minimal role of metallothionein in decreased chelator efficacy for cadmium.

Chelator efficacy in Cd poisoning drops precipitously if therapy is not commenced almost immediately after exposure. Metallothionein (MT), a low-molecular-weight metal-binding protein with high affinity for Cd, may be important for this phenomenon. To more fully assess this role of MT in the acute drop in chelator efficacy following Cd poisoning, rats were injected iv with radioisotopic Cd (1mg/kg as CdCl2; 50 muCi/kg) followed by diethylenetriaminepentaacetic acid (DTPA; 90 mg/kg ip) at various times (0, 15, 30, 60, and 120 min) after Cd. Ther percentage of the Cd dose remaining in major organs 24 hr following Cd was determined. Although DTPA reduced Cd content in the various organs when given immediately after Cd, the chelator was ineffective at all later times. Increases in hepatic and renal MT did not occur until 2 hr after Cd, and did not coincide with the earlier drop in chelator efficacy. Blockade of MT synthesis by actinomycin D treatment (1.25 mg/kg, 1 hr before Cd) failed to prolong the chelators effectiveness. Furthermore, newborn rats have high levels of hepatic MT which had no effect on the time course of chelator effectiveness since DTPA still decreased Cd organ contents if given immediately following Cd but had no effect if given 2 hr after Cd. Therefore, if appears that MT does not have an important role in the acute decrease in efficacy of chelation therapy for Cd poisoning. The quick onset of chelator ineffectiveness may be due to the rapid uptake of Cd into tissues which makes it relatively unavailable of chelation.

Animals↗
PubMed1983

Prealbumin as a biochemical marker of nutritional adequacy in premature infants.

To determine whether serum prealbumin would be useful in identifying adequacy of protein and calorie intake in premature infants, 17 infants between 26 and 33 weeks gestational age were studied throughout hospitalization. Serial anthropometric measurements, nutritional intake, and serum prealbumin concentrations were correlated. When mean intake of calories and protein was lower than 100 kcal/kg/day and less than 2 gm/kg/day, respectively, there was a significant difference in mean prealbumin values, compared with those in infants with a higher intake (P much less than 0.001). For infants with birth weights of 1000 gm or less, prealbumin correlated with protein intake (r = 0.66) and calorie intake (r = 0.64). In these infants, when protein intake exceeded 2 gm/kg/day, prealbumin concentrations increased to values reported for full-term infants in the first months of life. There was no significant correlation between intake of calories or protein and prealbumin values for infants born weighing greater than 1000 gm. Anthropometric measurements did not correlate with protein or calorie intake. We conclude that prealbumin is a sensitive measure of protein and calorie intake in premature infants, and that the definition of adequate nutrition may be different for premature infants of different birth weights and at various postconceptional ages.

Body Weight↗
PubMed1983

D-Lactic acidosis in children: an unusual metabolic complication of small bowel resection.

Acidosis caused by intestinal bacterial D-lactate production occurs in ruminants engorged with carbohydrate. A similar phenomenon was identified in two children who developed recurrent episodes of metabolic acidosis and peculiar neurologic symptoms in response to increased dietary carbohydrate after major small bowel resections. Both children were found to have elevated plasma concentrations of D-lactic acid at the time of each episode. Acid base and neurologic abnormalities responded immediately to neomycin therapy. Among a number of microorganisms isolated from stool cultures of these patients, one anaerobic Lactobacillus acidophilus species produced large amounts of D-lactate in vitro. Reduction in carbohydrate intake in one patient tested led to a fall in D-lactate generation. We believe that excessive D-lactate production by intestinal bacteria, from malabsorbed carbohydrate, may produce metabolic acidosis and neurologic symptoms in children with small bowel resections.

Acidosis↗