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Biomedical subjects

M A Lang

Publications and source records attributed to M A Lang.

At least 73 records · Page 4Linked to original sources
PubMed1984

Parenteral nutrition compared with transpyloric feeding.

Fifty nine infants of birthweight less than 1500 g were allocated alternately to initial total parenteral nutrition or to transpyloric feeding. Mortality was similar between the two groups. Ten of the 29 infants in the transpyloric group failed to establish full enteral nutrition during the first week of life. No beneficial effects on growth were shown in infants receiving parenteral nutrition. Acquired bacterial infection was higher in the parenteral group and associated with morbidity and mortality. Conjugated hyperbilirubinaemia occurred only in the parenterally fed infants. The incidence of necrotising enterocolitis was higher in the transpyloric group. Parenteral nutrition does not confer any appreciable benefit and because of greater complexity and higher risk of complications should be reserved for those infants in whom enteral feeding is impossible.

Body Weight↗
PubMed1984

Effect of different detergent systems on the molecular size of UDP glucuronosyltransferase and other microsomal drug-metabolizing enzymes.

Mouse liver microsomes were solubilized in various detergent systems, and the resulting aggregate structures associated with cytochrome P-450, cytochrome c reductase, and UDP glucuronosyltransferase were sized by gel filtration chromatography. Cholate or its derivative, CHAPS, in combination with Emulgen 911 or Lubrol 12A9 were necessary to generate a particle of about 140 k daltons, the smallest structure associated with cytochrome P-450. Cholate or CHAPS alone was sufficient to generate a minimally sized aggregate of 200 k daltons associated with NADPH cytochrome c reductase activity. Cholate in combination with Emulgen 911 or Lubrol 12A9 generated particles of about 280 k daltons associated with UDP glucuronosyltransferase activity. CHAPS alone also generated similarly sized particles under conditions in which UDP glucuronosyltransferase activity toward 1-naphthol and morphine was two to about twenty times greater, respectively, than with the combination of detergents. This finding suggests that the zwitterionic CHAPS is superior to other detergent systems for studies concerned with the purification of transferase enzymes, a microsomal system in which investigation of the number of different forms has been hampered by the instability of the enzyme upon solubilization and subsequent manipulation.

Animals↗
PubMed1982

Activation of misonidazole by rat liver microsomes and purified NADPH-cytochrome c reductase.

Rat liver microsomes and purified NADPH-cytochrome c reductase metabolized [14C]misonidazole anaerobically to a reactive intermediate that covalently binds to tissue macromolecules. Air strongly inhibited the binding whereas carbon monoxide had no effect, indicating that misonidazole is activated via reduction and not by cytochrome P-450-dependent oxidation. Both systems showed an absolute requirement for NADPH and were stimulated by flavine (FAD) and paraquat. The apparent Km for misonidazole binding to microsomal protein was 0.74 mM the apparent Vmax was 0.64 nmole 14C bound . mg-1 . min-1. At a single substrate concentration, nitrofurantoin, nitrofurazone and desmethylmisonidazole inhibited the covalent binding of misonidazole to microsomal protein by 47, 26, and 38% respectively. The effect of nitrofurantoin on the kinetics of misonidazole binding gave a complex interaction indicative of uncompetitive inhibition. Glutathione reduced the binding of misonidazole to microsomal protein below the level observed for boiled microsomes while ascorbic acid had no effect. Compared to nitrofurantoin and paraquat, misonidazole was a poor stimulator of superoxide production as measured by adrenochrome formation.

Animals↗
PubMed1981

Structural gene products of the Ah locus. Evidence for many unique P-450-mediated monooxygenase activities reconstituted from 3-methylcholanthrene-treated C57BL/6N mouse liver microsomes.

Cytochrome P-450 from cholate-solubilized liver microsomes prepared from 3-methylcholanthrene-treated genetically "responsive" C57BL/6N mice (Ahb/Ahb) was partially purified by aminooctyl-Sepharose 4B column chromatography with an elution buffer that included Emulgen 911, followed by hydroxylapatite column chromatography. The P-450 was separated into 16 fractions: 15 fractions principally associated with the Ahb allele and induction by 3-methylcholanthrene and 1 fraction not associated with the Ahb allele, i.e. predominantly constitutive form(s) of P-450. The metabolism of benzo[a]pyrene, 7-ethoxycoumarin, biphenyl, ethoxyresorufin, acetanilide, 2-acetylaminofluorene, phenacetin, estradiol-17 beta, and testosterone was investigated. With these nine substrates, we examined the rates of formation of 17 products, i.e. 17 P-450-mediated reconstituted monooxygenase "'activities," in each of the 16 fractions. Differing reductase/cytochrome and lipid/cytochrome requirements were observed for each activity; the reasons for these empirical differences are not known. By two-factor analysis of variance our data for 17 catalytic activities can be explained by a minimum of 19 unique groups of monooxygenase activities: 12 induced by 3-methylcholanthrene and 7 control (endogenous). At least one of these distinctly different 3-methylcholanthrene-induced groups and at least one of these constitutive groups is associated with a marked blue spectral shift (approximately 2.0 nm) in the Soret peak of the reduced hemoprotein.CO complex, suggesting multiple forms of inducible and control "P-448." Almost every reconstituted monooxygenase activity therefore appears to be unique and probably represents the aggregate activity from numerous forms of P-450.

Animals↗
PubMed1981

Effects of antidiuretic hormone on kinetic and energetic determinants of active sodium transport in frog skin.

The effects of antidiuretic hormone (ADH) on the rate of transepithelial active Na transport JaNa and the rate of suprabasal O2 consumption of Jsbr were studied in paired hemiskins of frog. Within some 30 min following administration of ADH both JaNa and Jsbr increased to near-maximal levels and then remained stable for at least an hour. On symmetric perturbation of the transepithelial electrical potential delta psi at 6-min intervals, the dependence of JaNa and Jsbr on delta psi was near-linear, both in control and experimental hemi-skins. The stability and near-linearity of the system permitted systematic analysis of the parameters of linear non-equilibrium thermodynamic (NET) and electrical equivalent circuit (EC) formulations. ADH (100 mU/ml) stimulated two of the three NET phenomenological L coefficients, as well as A, the affinity (negative Gibbs free energy) of a metabolic reaction driving transport. Observations at partially depressed levels of transport indicated that the effects of kinetic and energetic factors are to some extent discrete. EC analysis showed stimulation of the amiloride-sensitive conductance Ka, but not of the apparent electromitive force of Na transport 'ENa'. Similar effects were produced by 10 mU/ml of ADH or by 10 mM dibutyryl cyclic AMP, although less marked effects on the L coefficients were noted with the lower concentration of hormone. It is suggested that, in contrast to EC analysis, the NET formulation distinguishes between kinetic and energetic determinants of transport, supporting a dual mechanism of action of ADH.

Animals↗
PubMed1979

Evaluation of the rate of basal oxygen consumption in the isolated frog skin and toad bladder.

In the study of active transport it is important to distinguish between oxygen consumption sustaining transepithelial transport and that responsible for other tissue functions (basal metabolism). Since amiloride blocks transepithelial active sodium transport and the associated oxygen consumption in the frog skin and toad bladder, we and others have employed this agent to evaluate the rate of basal metabolism. This technique has recently been criticized in a report that amiloride (and ouabain) increased oxygen consumption when no sodium was available for transport. We have been unable to corroborate these observations. With magnesium-Ringer as external bathing solutions, amiloride and ouabain failed to stimulate oxygen consumption. With sodium-Ringer as external bathing solution amiloride reduced oxygen consumption about 30%, to a level indistinguishable from that found on external substitution of magnesium-Ringer for sodium-Ringer. We conclude that the use of amiloride permits evaluation of the rate of basal metabolism with acceptable accuracy; a possible slight depressant effect of ouabain on basal metabolism remains to be investigated.

Amiloride↗
PubMed1979

Measurement of oxygen consumption in voltage-clamped epithelia.

Standard apparatus for in vitro study of anuran epithelia was adapted for the incorporation of Clark oxygen electrodes, permitting the concurrent measurement of electrical current (active sodium transport) and oxygen consumption under voltage-clamp conditions, with independent manipulation of the two bathing solutions. Stability was enhanced by electrical isolation of the O2 electrodes, sensitive temperature control (+/- 0.03 degrees C), and constancy of stirring rate. Mean rate of drift was less than 3.7% of the average rate of basal (i.e., nontransport related) O2 consumption. In the present configuration the response time was less than 15 s. Visual fitting of slopes of O2 tension evaluated rates of O2 consumption with adequate accuracy in the physiological range (basal rates averaged about 20 pmol-s-1-cm-2 toad bladder, corresponding to about 10 pmol-s-1-mg-1 dry wt, or about 5 pmol-s-1-ml-1 chamber volume). Rpresentative slopes were read with a standard deviation of 3.5%.

Animals↗
PubMed1977

Thermodynamic analysis of active sodium transport and oxidative metabolism in toad urinary bladder.

Measurements of electrical current and oxygen consumption were carried out concurrently under voltage clamp conditions in 11 toad hemibladders. Inhibition of active transport with amiloride then permitted evaluation of the passive conductance and the rate of basal oxygen consumption Jbr, allowing the simultaneous determination of the rates of active sodium transport JaNa and suprabasal oxygen consumption Jsbr-JaNa and Jabr were linear functions of the electrical potential difference over a range of +/- 80 mV. This allowed the comprehensive application of a linear nonequilibrium thermodynamic formalism, leading to the evaluation of the affinity A (negative free energy) of the metabolic reaction driving transport, all phenomenological coefficients, and the degree of coupling q relating transport to metabolism. Values of A determined by two techniques were A1=56.0 +/- 5.8 and A2=58.2 +/- 6.5 kcal per mole. Values of q determined by two techniques agreed well and were less than 1, indicating incompleteness of coupling, and hence lack of fixed stoichiometry between Na transort and O2 consumption. The affinity and the electromotive force of sodium transport ENa are not closely correlated, reflecting the fact that ENa comprises both kinetic and energetic factors.

Animals↗
PubMed1977

Sodium transport and oxygen consumption in toad bladder. A thermodynamic approach.

The relationship between active sodium transport and oxygen consumption was investigated in toad urinary bladder exposed to identical sodium-Ringer's solution at each surface, while controlling the transepithelial electrical potential difference delta phi. Rates of sodium transport and oxygen consumption were measured simultaneously, both in the short-circuited state (delta phi = 0) and when delta phi was varied. Under short-circuit conditions, when the rates of active sodium transport changed spontaneously or were depressed with amiloride, the ratio of active sodium transport to the estimated suprabasal oxygen consumption Na/O2 was constant for each tissue, but varied among different tissues. Only when delta phi was varied did the ratio Na+/O2 change with the rate of active sodium transport; under these circumstances dNa+/dO2 was constant but exceeded the ratio measured at short-circuit [(Na+/O2)delta phi = 0[. This suggests that coupling between transport and metabolism is incomplete. The results are analyzed according to the principles of nonequilibrium thermodynamics, and intepreted in terms of a simple model of the transepithelial sodium transport system.

Animals↗
PubMed1975

Action of aldosterone on frog skin in the presence and absence of in vitro molting effects.

The molting which occurs in frog skin following exposure to high concentrations of aldosterone interferes with the interpretation of physiological measurements. Exposure of skins from frogs maintained in standard smooth tanks to 5 - 10(-7) M aldosterone caused within a few hours erratic responses in short-circuit current Io and conductance K followed by sustained stimulation of Io and K; 10(-8) M aldosterone caused only stimulation of Io and K. Storage of frogs in "rojgh tanks" eliminated in vitro molting on exposure to 5 - 10(-7) M aldosterone. IO and K were then superimposable for 3 h, after which Io increased far more rapidly than K. These results are consistent with an early effect on permeability of the active pathway and later effects on metabolism, either a direct effect on the pump or enhanced interaction between transport and metabolism.

Aldosterone↗
PubMed1969

Volume control by muscle fibers of the blue crab. Volume readjustment in hypotonic salines.

Single isolated muscle fibers from the walking legs of the blue crab, Callinectes sapidus act as Boyle-van't Hoff osmometers with an osmotically inactive volume of 33 %. Fibers in hypotonic salines undergo a spontaneous volume readjustment toward the initial volumes of the cells found in isotonic salines. The volume readjustment is initiated by the increase in cell volume in hypotonic salines and appears to be dependent on the duration of exposure of the fiber to external sodium, the sodium concentration, and the pH of the external medium. The volume-readjusted cells continue to behave as osmometers, but with an increased relative osmotically inactive volume and a decreased internal resistivity. The decreases in cell volumes appear to be, in large part, due to losses of osmotically active nonelectrolytes from the cells.

Animals↗