Strain Localization in Thin Films of Bi(Fe,Mn)O3 Due to the Formation of Stepped Mn(4+)-Rich Antiphase Boundaries.

The atomic structure and chemistry of thin films of Bi(Fe,Mn)O3 (BFMO) films with a target composition of Bi2FeMnO6 on SrTiO3 are studied using scanning transmission electron microscopy imaging and electron energy loss spectroscopy. It is shown that Mn(4+)-rich antiphase boundaries are locally nucleated right at the film substrate and then form stepped structures that are approximately pyramidal in three dimensions. These have the effect of confining the material below the pyramids in a highly strained state with an out-of-plane lattice parameter close to 4.1 Å. Outside the area enclosed by the antiphase boundaries, the out-of-plane lattice parameter is much closer to bulk values for BFMO. This suggests that to improve the crystallographic perfection of the films whilst retaining the strain state through as much of the film as possible, ways need to be found to prevent nucleation of the antiphase boundaries. Since the antiphase boundaries seem to form from the interaction of Mn with the Ti in the substrate, one route to perform this would be to grow a thin buffer layer of pure BiFeO3 on the SrTiO3 substrate to minimise any Mn-Ti interactions.

Free radical activity during development of insulin-dependent diabetes mellitus in the rat.

Free radical-induced lipid peroxidation was quantified by measuring expired pentane from diabetic prone BB Wistar rats of 45-90 d of age. Insulin-dependent diabetes mellitus was manifest at the age of 71 +/- 8 d. Expired pentane increased from 2.1 +/- 0.7 to 5.0 +/- 3.0 pmol/100g/min (p less than 0.01) at manifestation of the disease and remained high throughout the test period. In healthy age-matched control rats it persisted low. In rats made diabetic with streptozotocin, expired pentane remained low. The changes in expired pentane suggest that the development of endogenous insulin-dependent diabetes mellitus in BB rats is associated with increased free radical activity. This is not due to hyperglycemia or ketosis per se, and reflects a fundamental difference in the free radical activity between the spontaneously diabetic BB rats and the disease produced by streptozotocin. Development of spontaneous insulin-dependent diabetes in BB rats is associated with increased free radical activity that persists after the manifestation of the disease.

Correlation of free oxygen radical-induced lipid peroxidation with outcome in very low birth weight infants.

Lipid peroxidation was measured in 19 very low birth weight infants with respiratory distress syndrome by quantitating ethane and pentane in expired air during the first 5 days postnatally. Despite high levels of inspiratory oxygen, the ethane and pentane output was low within the first 24 hours; thereafter it increased up to 100 and 30 fold, respectively. On days 1 to 3 there was no detectable correlation between lipid peroxidation and fractional inspiratory oxygen. However, on days 4 and 5, lipid peroxidation and fractional inspiratory oxygen showed a significant correlation. Maximal amounts of expired ethane and pentane were significantly higher for patients with a poor outcome (five deaths, six cases of bronchopulmonary dysplasia) than for those with good outcome (eight infants surviving intact) (p less than 0.01). The results imply a role for free oxygen radicals in the pathogenesis of life-threatening complications in the very low birth weight infant.

Determination of ethane and pentane in free oxygen radical-induced lipid peroxidation.

It has been proposed that ethane and pentane reflect free oxygen radical-induced lipid peroxidation. However, methodological difficulties limit the use of these gases for assessment of free oxygen radical activity. In the present report we describe an improved method for the accurate analysis of picomole quantities (greater than or equal to 1 pmol) of ethane and pentane. They are first quantitatively trapped into an adsorbent and then heat-desorbed directly into a capillary column for gas chromatographic quantitation. During oxidation of linolenic (n-3) and linoleic (n-6) acid, ethane and pentane were formed, respectively. Nonstimulated granulocytes formed pentane. Upon addition of phorbol 13-myristate 12-acetate, the generation of pentane was increased by 540%. Addition of superoxide dismutase plus catalase inhibited lipid peroxidation in both a cell-free system and in isolated cells. The present method is useful in the evaluation of free oxygen radical induced damage.

Membrane potential generation and calcium transport in plasma membrane enriched fractions from fetal human brain.

Plasma membrane fractions isolated from fetal human brain of 14-19 weeks of gestation are capable of generating a membrane potential of 30-50 mV as a response to a gradient of K+ ions. Valinomycin, a K+ conducting ionophore, does not affect the membrane potential whereas it is markedly reduced by veratridine which opens Na+ channels in excitable membranes. The membrane fractions concentrate Ca2+ by an ATP-dependent mechanism. The uptake has a high affinity for Ca2+, it is enhanced by oxalate and abolished by the 2H+/Ca2+ exchanger A 23187. Trifluoroperazine (40 microM), a calmodulin antagonist, inhibits Ca2+ uptake by 80%. Addition of Na+ causes efflux of part of the Ca2+ taken up in the presence of ATP, suggesting that a Na+-linked Ca2+ transport is also present in the membranes. The results show that the neuronal membranes of the fetal human brain already in the early second trimester of gestation have properties similar to those of the adult animal brain.

beta-Adrenergic induction of tyrosine aminotransferase organ culture of fetal rat and fetal human liver.

Isoproterenol, phenylephrine, and salbutamol (all 100 microM) induced the activity of tyrosine aminotransferase (TAT; EC 2.6.1.5) by 109%, 72%, and 141%, respectively, in organ culture of fetal human liver. Propranolol (100 microM) inhibited the effects of isoproterenol and phenylephrine. In organ culture of fetal rat liver, the induction of TAT activity by phenylephrine (100 microM) was not significantly affected by phentolamine (100 microM), whereas it was abolished by a combination of phentolamine and propranolol (both 100 microM). Isoproterenol and salbutamol caused significant increases in TAT activity, which were not affected by 100 microM atenolol but were completely inhibited by propranolol (100 microM). The results show that the fetal human liver has developed responsiveness to adrenergic stimuli at the 12th week of gestation. The adrenergic induction of TAT in fetal human liver is mediated solely by beta-adrenergic mechanisms. In the fetal rat liver, the adrenergic induction of TAT is mediated by beta 2-adrenergic receptors.

Purification and properties of human liver tyrosine aminotransferase.

Tyrosine aminotransferase (EC 2.6.1.5) of human liver was purified 2200-fold by successive chromatography on DEAE-cellulose DE-52, Ultrogel AcA-34, CM-Sephadex C-50 and hydroxyapatite to a specific activity of 64 units/mg of protein. The purified enzyme had a molecular mass of 95 500. The Km-values were 1.04 X 10(-3) mol/l, 0.17 X 10(-3) mol/l and 0.69 X 10(-6) mol/l for tyrosine, 2-oxoglutarate and pyridoxal 5'-phosphate, respectively. In the final purification step the enzyme activity was divided into two major fractions and a minor third one. On isoelectric focusing, three distinct fractions of specific tyrosine aminotransferase activity were obtained. The isoelectric points of these fractions were 4.9, 5.1 and 5.3, respectively. These findings imply that the human tyrosine aminotransferase consists of three subforms. No differences in properties studied could be found between the subforms. The coenzyme, pyridoxal 5'-phosphate, could be removed by dialysis.

Development of tyrosine aminotransferase and para-hydroxyphenylpyruvate dioxygenase activities in fetal and neonatal human liver.

In livers of fetuses of 220--340 g body wt, total cytosolic tyrosine aminotransferase activity was 1.0 nmol of product/mg of protein per min, and the corresponding values for autopsy livers of newborns of 740--1,475 g and 2,600--3,650 g were 1.5 and 5.7, respectively, as compared with the adult value of 12.7. On the other hand, para-hydroxyphenylpyruvate dioxygenase activity is at adult level already in fetuses less than 340 g body wt. The Km value for tyrosine of tyrosine aminotransferase (1 mM) was considerably higher than the corresponding value for para-hydroxyphenylpyruvate of para-hydroxyphenylpyruvate dioxygenase (50 micro M). These results suggest that tyrosine aminotransferase is the rate limiting enzyme in the catabolism of tyrosine in premature infants.

Induction of cytosolic tyrosine aminotransferase by dexamethasone in organ culture of fetal human liver.

Total tyrosine aminotransferase activity in organ culture of fetal human liver is increased by 347% after 15 h incubation with 2 micro M of dexamethasone. Isoelectric focusing reveals that the increased activity is due to induction of cytosolic tyrosine aminotransferase (EC 2.6.1.5) while the activity of the nonspecific mitochondrial aspartate aminotransferase (EC 2.6.1.1) remains unchanged.

Metabolic basis of hypertyrosinemia in liver disease.

Serum tyrosine concentrations in patients with liver cirrhosis and with advanced fatty degeneration of the liver were 143 and 140 mumol/L, respectively, as compared with 65 mumol/l in normal controls. In biopsy samples of histologically normal livers, total tyrosine aminotransferase activity was 10.5 +/- 1.8 nmol p-hydroxyphenylpyruvate formed/mg of protein per min (mean +/- SEM; n = 10) whereas the corresponding figures for 7 cirrhotics were 4.95 +/- 0.85. The enzyme activity was normal in moderate adipose degeneration of the liver, but it was reduced when more than 50% of the hepatocytes were occupied by fat. It is suggested that the hypertyrosinemia of cirrhotics is, at least in part, due to decreased tyrosine aminotransferase activity.

Tyrosine aminotransferase activity in human fetal liver.

There are at least two enzymes in adult human liver that transaminate tyrosine: cytoplasmic tyrosine aminotransferase (EC 2.6.1.5) and mitochondrial aspartate aminotransferase (EC 2.6.1.1). Total tyrosine aminotransferase activity in the supernatant fraction of adult human liver was 19.8 nmol of p-hydroxyphenylpyruvate formed per min/mg of protein as compared to 0.53 in fetuses of 12--22 weeks of gestational age and 2.0 in the newborn. The presence of specific tyrosine aminotransferase (EC 2.6.1.5) could be demonstrated by isoelectric focusing techniques in fetal human liver during the first trimester. No specific tyrosine aminotransferase could be detected in the placenta. Total tyrosine aminotransferase activity was elevated by dexamethasone and tyrosine administration to organ cultures of fetal liver.

Regulation of tyrosine aminotransferase in foetal rat liver.

A specific tyrosine aminotransferase, separate from the aspartate aminotransferases, is present in low concentration in foetal rat liver at the 21st day of gestation. Intraperitoneal injections of tyrosine methyl ester into the foetuses in utero increase the activity 2-fold, whereas glucose injections decrease it. Tyrosine, dexamethasone and dibutyryl cyclic AMP induce the enzyme activity in organ culture to the same extent as in adult rat liver in vivo.

Post-traumatic bone mineral loss in tibial shaft fractures treated with a weight-bearing brace.

The bone mineral content in the upper ends of the tibia and the fibula was measured in 27 patients with tibial shaft fracture. The loss of bone mineral associated with the fracture did not differ between patients who were allowed weight-bearing in a functional below-knee brace and patients treated with a long leg plaster cast without weight-bearing.

Changes in bone mineral content following tibia shaft fractures.

The bone mineral content of the upper ends of the tibia and the fibula was measured in 27 patients with tibia shaft fracture. The bone mineral decreased rapidly after fracture, the loss continuing for about 5 months. Later, towards the end of the first year after the injury, there was a slow restoration of mineral but no return to initial values in most instances. Although the average maximum loss was approximately 45%, only 25% of the initial bone mineral was missing after one year.

Changes in bone mineral content following ligamentous knee injuries.

In 44 patients with clinical signs of ligamentous injuries to the knee-joint without fracture, the bone mineral content was measured by gamma absorptiometry in the proximal end of the tibia and the fibula. The injuries caused a loss of an average 10% in those patients who had no signs of complete tears of knee ligaments and were therefore treated only with an ace-bandage and for a shortime, whereas the loss was 18% in those who were operated on with repair of ligamental injuries followed by plaster immobilization. Repeated injuries did not seem to cause further loss of mineral. There were no signs of restoration within the first year. The pre-injury bone mineral content was in these patients above that of an unselected control population, however, the post-traumatic loss of mineral brought the values down into a normal range.

Partial purification and properties of frog liver tyrosine aminotransferase.

Hepatic tyrosine aminotransferase of the frog Rana temporaria was partially purified by (NH4)2SO4 fractionation and successive chromatography on DEAE-cellulose DE-52, Ultrogel AcA-34, DEAE-cellulose DE-52 again and, finally, hydroxyapatite. During the last step, the enzyme activity separated into two fractions; traces of a third fraction were also found. The major form was purified 6000-fold to a specific activity of 200 units/mg of protein; it was about 50% pure by electrophoretic criteria. It had mol.wt. about 85 000 as determined by gel filtration on a Sephadex G-100 column. It was not activated by added pyridoxal 5'-phosphate. The enzyme was, however, inactivated by the pyridoxal phosphate reactants canaline and amino-oxyacetate. The enzyme was specific for 2-oxoglutarate as the amino group acceptor. Homogentisate inhibited the enzyme and adrenaline was an activator; both effects were seen at low concentrations of the effectors. The relationship between initial rate and tyrosine or 2-oxoglutarate concentration was abnormal and complex. Form-2 enzyme had similar or identical molecular weight, cofactor requirements, oxo acid specificity and kinetics.