PubMed Health⌕ Search

Biomedical subjects

C H Blomquist

Publications and source records attributed to C H Blomquist.

At least 37 records · Page 2Linked to original sources
PubMed1986

Fetal lung maturity assessment by a modified A650 determination.

This paper presents an evaluation of a modified absorbance method for estimating fetal lung maturity. Absorbance at 650 nm in combination with a two-step centrifugation procedure was used in an attempt to focus more directly on lamellar bodies and evaluate the contribution of residual absorbance due to non-lamellar body materials. Absorbance values after centrifugation at 250 X g for 5 minutes (A250) and 10,000 X g for 20 minutes (A10,000) were taken as estimates of total absorbance due to lamellar bodies plus non-lamellar body material and that due to non-sedimentable, non-lamellar body material respectively. These values were used to generate two new parameters: delta A (A250-A10,000), to better estimate absorbance due to lamellar bodies, and %A (delta A/A250 X 100), to express lamellar body absorbance in terms of total observable absorbance and thereby minimize effects of dilution. The three parameters (A250, delta A, %A) were used in combination to create a battery (ABatt) of absorbance values for each fluid sample. Absorbance after centrifugation at 2,000 X g for 10 minutes (A2,000), a widely used standard method, was also evaluated for purposes of comparison. A250 was designated as mature if greater than or equal to 0.350, delta A was called mature if greater than or equal to 0.250, and %A was considered mature if greater than or equal to 75%. If any of the parameters was immature, ABatt was called immature. The range of values for A250, A2,000, and A10,000, increased with gestational age in the total population as well as the corrected population (excluding amniotic fluid contaminants, and pregnancies with isoimmunization or diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Amniotic Fluid↗
PubMed1986

Mannitol pharmacokinetics and serum osmolality in dogs and humans.

The relationship between mannitol pharmacokinetics and changes in serum osmolality were studied in dogs and humans. Four human subjects each received between 0.5 and 0.7 g/kg of mannitol as an i.v. infusion given over 15 min. Intravenous bolus doses of 0.5, 1.0 and 1.5 g/kg were given to each of five animals. Serial determinations of serum osmolality and serum mannitol concentrations were then performed. Mannitol disposition was best described using a biexponential equation and assuming a two-compartment, open model with elimination from the central compartment. For human subjects, the mean (+/- S.D.) distribution half-life was 2.11 +/- 2.67 min and the elimination half-life was 71.15 +/- 27.02 min. The volume of distribution was 0.47 +/- 0.50 liters/kg and total body clearance was 7.15 +/- 10.23 ml X min-1 X kg-1. The disposition of mannitol in dogs is similar to that observed in humans. Mannitol clearance was independent of dose whereas the central compartment volume was significantly larger (P less than .005) in animals receiving the 1.5-g/kg dose. The volume change is probably due to a rapid, uncompensated shift of water from intracellular to extracellular space. There was a strong positive correlation (r = 0.90) between mannitol concentration and serum osmolality changes. However, neither maximum serum mannitol concentration nor maximum serum osmolality increased proportionately with dose. Only the 1.5-g/kg dose produced a sustained elevation of serum osmolality, confirming that larger doses are more likely to result in prolonged hypertonic dehydration.

Adult↗
PubMed1985

17 beta-hydroxysteroid and 20 alpha-hydroxysteroid dehydrogenase activities of human placental microsomes: kinetic evidence for two enzymes differing in substrate specificity.

During storage at 4 degrees C, the 17 beta-hydroxysteroid dehydrogenase activity of human placental microsomes with estradiol-17 beta was more stable than that with testosterone. In order to evaluate the basis for this difference, kinetics with C18-, C19-, and C21- steroids as substrates and/or inhibitors was studied in conjunction with an analysis of the effects of detergents. Both 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) and 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) activities were detected. At pH 9.0, apparent Michaelis constants were 0.8, 1.3, and 2.3 microM for estradiol-17 beta, testosterone, and 20 alpha-dihydroprogesterone, respectively, 17 beta-HSD activity with testosterone was inhibited by estradiol-17 beta, 5 alpha-dihydrotestosterone, 5 beta-dihydrotestosterone, 20 alpha-dihydroprogesterone, and progesterone. In each case 90 to 100% inhibition was observed at 50 to 200 microM steroid. Activity with 20 alpha-dihydroprogesterone was similarly sensitive to inhibition by C19-steroids. By contrast, 25 to 45% of the activity with estradiol-17 beta was not inhibited by high concentrations of C19- or C21-steroids and differed from the 17 beta-HSD activity with testosterone and the major fraction of that with estradiol-17 beta by being insensitive to solubilization by detergent. These results are consistent with an association of two dehydrogenase activities with human placental microsomes. One recognizes C18-, C19-, and C21-steroids as substrates with comparable affinities. The second appears to be highly specific for estradiol-17 beta. The former activity may account for most if not all of the oxidation-reduction at C-17 of C19-steroids and at C-20 of C21-compounds at physiological concentrations by term placental tissue.

17-Hydroxysteroid Dehydrogenases↗
PubMed1985

Inactivation of soluble 17 beta-hydroxysteroid dehydrogenase of human placenta by fatty acids.

The sensitivity of soluble, 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) of human placenta to inactivation by fatty acids was examined. Exposure to the unsaturated fatty acids oleic, arachidonic, linoleic and linolenic acid resulted in the loss of activity. Methyl and ethyl esters of oleic acid, the saturated fatty acid, stearic acid and prostaglandins E2 and F2 alpha were without effect. Inactivation by oleic acid required the fatty acid at levels above its critical micelle concentration, 50 microM, as estimated by light-scattering. Steroid substrates and inhibitors did not protect against inactivation. NAD+, NADH, NADP+ and NADPH did protect. The concentrations of NADP+, 50 microM, and NAD, 1.5 mM, necessary for complete protection were significantly greater than their respective Michaelis constants, 0.16 microM and 15.2 microM. The data suggest that soluble 17 beta-HSD can bind to fatty acid micelles and that the binding site(s) on the enzyme are at or near pyridine nucleotide binding sites.

17-Hydroxysteroid Dehydrogenases↗
PubMed1984

Inhibition of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activities of human placenta by steroids and non-steroidal hormone agonists and antagonists.

Various naturally occurring steroids, synthetic steroid derivatives and non-steroidal hormone agonists and antagonists were assayed as inhibitors of human placental 17 beta-HSD activities. Microsomal 17 beta-HSD was inhibited by C18-, C19- and C21-steroids. Soluble 17 beta-HSD was highly specific for C18-steroids. In contrast to the soluble activity, the microsomal enzyme also had a strong affinity for ethinylestradiol (KI = 0.3 microM) and danazol (KI = 0.6 microM); anabolic steroids and norethisterone were weaker inhibitors. Of the non-steroids tested only diethylstilbestrol and o-demethyl CI-680 were inhibitors and they showed a greater affinity for soluble 17 beta-HSD. KI-values for estradiol-17 beta, (0.8 microM), progesterone (27.0 microM) and 20 alpha-dihydroprogesterone (1.5 microM) were comparable to reported tissue levels of these compounds, consistent with a possible competition in vivo among naturally occurring C18-, C19-, and C21-steroids for the active site of microsomal 17 beta-HSD.

17-Hydroxysteroid Dehydrogenases↗
PubMed1983

Characterization of a nonenzymatic component in the isomerization of 5-pregnene-3,20-dione catalyzed by human placental microsomes in vitro.

When human placental microsomes were heated in boiling water or exposed to trypsin, 30 to 40% of the 5-ene,3-ketosteroid isomerase activity was stable. Aqueous suspensions of chloroform:methanol extracts of microsomes also catalyzed isomerization of 5-pregnene-3,20-dione, activity being associated with the polar lipid fraction. The trypsin- and heat-stable activities, as well as that of resuspended microsomal lipids, showed a dependence on buffer composition and concentration. Little activity was detected in water at pH 7.0. Relative activities in various buffers were Hepes (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) greater than Pipes (1,4-piperazinediethanesulfonic acid) greater than potassium phosphate greater than Mes(4-morpholineethanesulfonic acid). The data suggest that the occurrence of membrane lipid-dependent nonenzymatic catalysis could contribute to the isotope exchange with solvent observed in previous studies of the mechanism of isomerization catalyzed by placental microsomes. The ability of the membrane lipid phase to catalyze steroid isomerization under certain conditions and the fact that this activity is subject to modifications by exogenous agents may have more general implications for an understanding of possible effects of xenobiotics on steroid hormone formation and action in vivo.

Buffers↗
PubMed1982

Inactivation of microsomal 17 beta-hydroxysteroid dehydrogenase by phospholipase C: rates of phospholipid hydrolysis and enzyme inactivation, and effects of phospholipids.

When guinea-pig liver microsomes were exposed to phospholipase C the rate of phospholipid hydrolysis exceeded the rate of decrease in 17 beta-hydroxysteriod dehydrogenase (17 beta-HSD) activity. The time-course of the decrease in 17 beta-HSD activity was biphasic. An initial more rapid decrease (30-50% of total) was associated with the major extent (85%) of phospholipid hydrolysis. Subsequently, a second, slower phase of 17 beta-HSD inactivation was observed. The addition of purified phospholipids did not reactivate 17 beta-HSD but did protect against the inactivation seen in the second phase. The diacyglycerides produced by phospholipase C action remained associated with the microsomes. It is proposed that the differences in the rates of 17 beta-HSD inactivation reflect variations in the distribution of a single form of 17 beta-HSD among differing membrane fractions rather than the existence of multiple enzyme forms. The stabilizing effects of phospholipids may be due to their ability to prevent changes in lipid-lipid, lipid-protein and protein-protein interactions resulting from diacylglyceride formation. Resuspended microsomal lipids (chloroform-methanol extracts) inactivated 17 beta-HSD suggestive of the presence of endogenous lipid modulators of enzymatic activity.

17-Hydroxysteroid Dehydrogenases↗
PubMed1982

Circadian rhythm in urinary N-acetyl-beta-glucosaminidase (NAG) of clinically healthy subjects. Timing and phase relation to other urinary circadian rhythms.

Urinary N-acetyl-beta-glucosaminidase (NAG), a lysosomal enzyme of renal tubular origin, has been shown to be a sensitive indicator of renal tubular function. This study documents a circadian rhythm in the urinary activity of NAG, statistically validated and quantified by the cosinor method, in 19 female and 15 male human subjects. The acrophase of the circadian rhythm in urinary NAG activity occurs at 09(40) with 95% confidence limits between 08(40) and 12(08) and is similar to the timing of the circadian rhythm in urinary free cortisol. The circadian acrophase of urinary NAG activity lags in timing the circadian rhythms in urine volume, Na and K excretion, and urinary free adrenalin and noradrenalin, by about five to ten hours and the circadian rhythm in creatinine excretion by about 11 hours. These functions with their characteristic phase relations are part of the internal circadian time structure of the human organism, and may provide internal phase references, independent of the "time of day." This study also documents a sex difference in mesor of the circadian rhythms in urinary NAG activity, with female subjects having a higher mesor and amplitude than the male subjects, and in the excretion of creatinine and potassium, with male subjects having a higher mesor and amplitude than the female subjects.

Acetylglucosaminidase↗
PubMed1982

Use of renal enzymes to evaluate nephrotoxicity in lithium treated patients.

N-acetyl-beta-glucosaminadase (NAG) is a renal enzyme which is an early, sensitive and reliable indicator of renal damage. NAG assays of midstream spot urines were not significantly different in a group of controls when compared to patients starting lithium for the first time, or to a group of patients who had been taking lithium for more than one year. However, a small number of lithium-treated patients may have evidence of renal damage, identifiable by NAG assay.

Acetylglucosaminidase↗
PubMed1982

Reduction of cis-diamminedichloroplatinum nephrotoxicity in rats by optimal circadian drug timing.

A prominent circadian rhythm in the nephrotoxicity of a therapeutic dose of cis-diamminedichloroplatinum (cisplatin) is demonstrated in female Fischer rats. Rats were randomized to receive two doses of either cisplatin or 0.9% NaCl solution 14 days apart at the times of either high or low values in their circadian rhythm of urinary volume. Toxicity was assessed by measuring changes in body weight and changes in the 24-hr means of urinary volume, blood urea nitrogen, and urinary beta-N-acetylglucosaminidase (NAG) activity. Toxicity was least in rats which received the drug near the circadian maximum of urinary volume. Conversely, rats which received the same dose of drug near the circadian minimum of urinary volume lost more weight and exhibited a 2-fold increase in the 24-hr mean of urinary volume, a 3-fold rise in the 24-hr mean of blood urea nitrogen, and a 5-fold increase in the 24-hr mean of urinary NAG activity. A positive correlation between urinary NAG at the time of cisplatin administration and the extent of cisplatin nephrotoxicity was demonstrated (p less than 0.02). A correlation also was found between tissue NAG concentration and tissue uptake of cisplatin (p less than 0.001). A marked circadian rhythm of NAG activity in proximal tubular cells may contribute to the prominent circadian rhythm in murine renal tolerance for cisplatin.

Acetylglucosaminidase↗
PubMed1981

Improved enzymatic method for determining mannitol and its application to dog serum after mannitol infusion.

An enzymatic method for mannitol quantitation has been developed. Its application mannitol levels in serum samples from dogs after mannitol infusion is illustrated. The method is based on the spectrophotometric measurement of the initial rate of NADH formation in the reaction between mannitol and NAD catalyzed by mannitol dehydrogenase. A linear relationship between initial rates and mannitol concentration is seen between 17 mumol/l and 6.7 mmol/l mannitol. From the extent of dilution of the serum sample in the assay this corresponds to serum levels of 0.5 to 200 mmol/l. Because of the high degree of substrate specificity of mannitol dehydrogenase and the extensive dilution of the serum sample in the assay reaction mixture, serum proteins and glucose do not interfere with the reaction. As a result, pre-treatment of samples to remove glucose and deproteinization are necessary.

Animals↗
PubMed1980

The effects of betamethasone on fetal development in the rabbit.

Pregnant rabbits were injected with either 0.8 mg of betamethasone or with a comparable volume of saline on days 24 and 25 of gestation and delivered by cesarean section on day 26. There was a significant reduction in the weight of fetuses and in the weights of fetal brain, lungs, liver, and placenta in betamethasone-treated animals. With respect to the fetal brain, the concentration of DNA, the average of cell number, cell size, cell weight, and cell phospholipids were unaffected whereas the concentrations of phospholipids and protein were elevated in the treatment group.

Animals↗
PubMed1980

Phospholipase A2 inactivation of microsomal 17 beta-hydroxysteroid oxidoreductase: rates of phospholipid hydrolysis and enzyme inactivation, effects of hydrolysis products and properties of the phospholipase A2-treated enzyme.

Exposure of guinea pig liver microsomes to phospholipase A2 resulted in the nearly complete loss of 17 beta-hydroxysteroid oxidoreductase (17 beta-HSD) activity, the time course of which correlated with phospholipid hydrolysis and lysolecithin formation. Lysolecithin and unsaturated fatty acids added to microsomes also inactivated 17 beta-HSD indicating that they may contribute to the inactivation by phospholipase A2. If exposure to lysolecithin and fatty acids was minimized by including serum albumin in the reaction mixture, phospholipids were rapidly hydrolyzed; but in this case the extent of 17 beta-HSD inactivation was less and the rate of loss was significantly slower. The data suggest that phospholipid hydrolysis per se results in a destabilization of 17 beta-HSD resulting in the subsequent activity loss. The inactivation of 17 beta-HSD by lysolecithin and fatty acids has not been reported previously and is suggestive of a possible control mechanism in vivo.

17-Hydroxysteroid Dehydrogenases↗