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Biomedical subjects

J Butler

Publications and source records attributed to J Butler.

At least 379 records · Page 21Linked to original sources
PubMed1977

Mechanism of the reaction of hydrated electrons with ferrocytochrome c.

1. The hydrated electron reacts with ferrocytochrome c to form an unstable intermediate. This intermediate decays in a first-order manner to give, in the first instance, a product which has a similar absorption spectrum in the range 400-610 nm as normal ferricytochrome c. 2. At 21 degrees C the rate constant for the reaction of hydrated electrons with ferrocytochrome c at pH 7.4 (2 mM phosphate buffer) is (3.0 +/- 0.3) = 10(10) M-1 - S-1. As the pH is increased above pH 8.0 the rate constant steadily decreases. The dependence of the rate constant on pH can be explained if ferrocytochrome c has a pK of around 9.2. 3. At 21 degrees C and pH 7.4, the rate constant for the decay of the intermediate is (1.40 +/- 0.15) - 10(5) S-1. This reaction shows no pH dependence in the range 6-2-11.0. 4. A mechanism is proposed whereby the central metal atom of the ferrocytochrome c is oxidased and a thioether bond is reduced. The resulting ferricytochrome c species then slowly develops an absorbance at 606 nm due to the attack of the sulfhydryl group on the haem.

Animals↗
PubMed1977

5-oxoprolinuria: biochemical observations and case report.

We have studied a patient with 5-oxoprolinuria who presented with hemolysis and metabolic acidosis as a neonate; he has had normal growth and development to one year of age. Compensated hemolytic anemia persists, and he requires alkalinizing agents for correction of acidosis. Biochemical studies have confirmed that a deficiency of glutathione synthetase is responsible for the 5-oxoprolinuria. Genetic heterogeneity was apparent on comparative study of glutathione synthetase kinetics in cells from two patients with this disorder. The consequences of the deficiency of glutathione synthetase, decreased intracellular glutathione, and overproduction of 5-oxoproline are discussed with reference to the possible cellular roles of these compounds.

Acidosis↗
PubMed1977

Mechanism of change in pulmonary shunt flow with hemorrhage.

In the presence of regional atelectasis, hemorrhage increases the pulmonary shunt fraction (Qs/Qt). We wanted to determine if the increase in Qs/Qt occurs due to inhibition of hypoxic vasoconstriction or due to hydrostatic effects associated with a collapsed lung and decrease in cardiac output. We compared the effects of hemorrhage on flow to a hypoxic lung (Qh) produced in two ways in anesthetized dogs. In six dogs atelectasis of one lung was produced by bronchial occlusion and in a second group of six dogs one lung was ventilated with 100% nitrogen. The other lung in each group was ventilated with 100% nitrogen. The other lung in each group was ventilated with 100% O2. Hemorrhage (20 ml/kg) had no effect on Qh/Qt in dogs with a nitrogen-ventilated lung suggesting that hemorrhage did not inhibit hypoxic vasoconstriction. In contrast, hemorrhage caused a marked increase in Qh/Qt in dogs with a collapsed lung because the flow to the inflated ventilated lung fell, while flow to the collapsed lung did not change. The increase in Qs/Qt in the dogs with atelectasis can be explained solely on the basis of mechanical effects produced by the differences in lung heights and alveolar pressures between ventilated and atelectatic lung.

Animals↗
PubMed1977

Pulmonary arteriovenous fistulas: increase in shunt at high lung volume.

Intrapulmonary shunt measured in the sitting position by the oxygen breathing method increased at total lung capacity in 7 of 8 patients with pulmonary arteriovenous fistulas. This may explain the clinically noted increased murmur over a fistula on inspiration. The finding of an increased intrapulmonary shunt at total lung capacity might suggest the diagnosis in equivocal cases and provide a convenient test for follow-up after surgery.

Arteriovenous Fistula↗
PubMed1976

The kinetics of the reduction of cytochrome c by the superoxide anion radical.

1. At neutral pH ferricytochrome c is reduced by the superoxide anion radical (O2-), without loss of enzymatic activity, by a second order process in which no intermediates are observed. The yield of ferrocytochrome c (82-104%), as related to the amount of O2- produced, is slightly dependent on the concentration of sodium formate in the matrix solution. 2. The reaction (k1 equals (1.1+/-0.1) - 10(6) M-1 - s-1 at pH 7.2, I equals 4 mM and 21 degrees C) can be inhibited by superoxide dismutase and trace amounts of copper ions. The inhibition by copper ions is removed by EDTA without interference in the O2- reduction reaction. 3. The second-order rate constant for the reaction of O2- with ferricytochrome c depends on the pH of the matrix solution, decreasing rapidly at pH greater than 8. The dependence of the rate constant on the pH can be explained by assuming that only the neutral form of ferricytochrome c reacts with O2- and that the alkaline form of the hemoprotein is unreactive. From studies at pH 8.9, the rate for the transition from the alkaline to the neutral form of ferricytochrome c can be estimated to be 0.3 s-1 (at 21 degrees C and I equals 4 mM). 4. The second-order rate constant for the reaction of O2- with ferricytochrome c is also dependent on the ionic strength of the medium. From a plot of log k1 versus I1/2-(I + alphaI1/2)-1 we determined the effective charge on the ferricytochrome c molecule as +6.3 and the rate constant at I equals 0 as (3.1+/-0.1) - 10(6) M-1 - s-1 (pH 7.1, 21 degrees C). 5. The possibility that singlet oxygen is formed as a product of the reaction of O2- with ferricytochrome c can be ruled out on thermodynamic grounds.

Animals↗
PubMed1975

The reaction between the superoxide anion radical and cytochrome c.

1. The superoxide anion radical (O2-) reacts with ferricytochrome c to form ferrocytochrome c. No intermediate complexes are observable. No reaction could be detected between O2- and ferrocytochrome c. 2. At 20 degrees C the rate constant for the reaction at pH 4.7 to 6.7 is 1.4-10(6) M-1. S -1 and as the pH increases above 6.7 the rate constant steadily decreases. The dependence on pH is the same for tuna heart and horse heart cytochrome c. No reaction could be demonstrated between O2- and the form of cytochrome c which exists above pH approximately 9.2. The dependence of the rate constant on pH can be explained if cytochrome c has pKs of 7.45 and 9.2, and O2- reacts with the form present below pH 7.45 with k = 1.4-10(6) M-1 - S-1, the form above pH 7.45 with k = 3.0- 10(5) M-1 - S-1, and the form present above pH 9.2 with k = 0. 3. The reaction has an activation energy of 20 kJ mol-1 and an enthalpy of activation at 25 degrees C of 18 kJ mol-1 both above and below pH 7.45. It is suggested that O2- may reduce cytochrome c through a track composed of aromatic amino acids, and that little protein rearrangement is required for the formation of the activated complex. 4. No reduction of ferricytochrome c by HO2 radicals could be demonstrated at pH 1.2-6.2 but at pH 5.3, HO2 radicals oxidize ferrocytochrome c with a rate constant of about 5-10(5)-5-10(6) M-1 - S-1.

Animals↗
PubMed1975

Respiratory function in pregnant obese women.

Lung volumes and other ventilatory variables were measured in 10 women with a mean age of 28 years, a mean height of 163 cm., and weights which were 50 to 140 per cent above the normal. Measurements were made during the last trimester of pregnancy and after the second month postpartum. Mean values of lung volumes in liters during these two time periods were: vital capacity (VC), 3.7 and 3.92; expiratory reserve volume (ERV), 0.79 and 0.94; functional residual capacity (FRC), 2.06 and 2.14; and forced expiratory volume at one second (FEV1) 3.2 and 3.3. Mean blood gas values were as follows: pH, 7.44 during both times; PaCO2, 29.7 and 35 torr; standard bicarbonate, 22 and 28.8 mEq; base excess, -4.2 and 0.03 PaO2 breathing air, 85 and 86 and breathing 100 per cent oxygen, 527 and 515 torr; AaDO2, 162 and 167 torr. We conclude that, with the exception of FRC, pregnant obese women who are 50 to 140 per cent overweight develop respiratory changes similar to those seen in normal-weight gravidas. These findings suggest that obesity of this magnitude does not exaggerate changes in ventilation induced by pregnancy as generally believed. Why in this obese population the decrease in FRC during pregnancy did not occur to the same degree as that seen in normal-weight gravidas cannot be defined from our study. Evidence is presented for a ventilation/perfusion imbalance in obese subjects which is not corrected during pregnancy.

Adult↗
PubMed1975

Variability of routine pulmonary function tests.

Pulmonary function tests sometimes indicate a progressive deterioration and at other times a 'stepwise' worsening which may be followed by improvement. Interpretation depends on the extent of random or diurnal variations in function. Routing pulmonary function tests (VC, FEV1, FRC, and airway resistance (Raw)) were repeatedly measured in normal subjects, patients with stable irreversible airways obstruction, and patients with stable restrictive disease. In all groups there was a significant (P less than 0.001) diurnal variation in Raw, with high values in the morning, low values at noon, and rising values in the evening. The midday Raw values were about 80% of the highest daily values. The considerable random and diurnal variability seen in all tests is reflected in the range of high and low values (% of mean individual response) in individuals. The largest variation in an individual between measurements taken at two different times was 81% in Raw (range: 40% above to 41% below the mean). There was less variation in FEV1 (29%), FRC (62%), and VC (30%). Thus the finding of a stepwise change in function could reflect its natrual variability. When repeated studies are done to assess progress or the effects of therapy on disease, there are many factors, including the time of day at which the tests are performed, which should be standardized as far as possible.

Air Pollution↗
PubMed1975

Pulmonary venous waterfall and perivenous pressure in the living dog.

Evidence has been obtained that a waterfall effect occurs in the pulmonary veins of the living dog. Anesthetized open-chest dogs were used. Small catheters were passed from the left atrium retrogradely up the pulmonary veins and venous tributaries until they finally pierced the venous walls. They were then pulled out through the surface of the lung until their bellshaped inner ends wedged in small side branches of the vein. They were used to measure upstream venous pressures via the occluded tributary without occlusion of the vein. The pulmonary lymphatics and bronchial circulation were untouched. Alveolar pressure (transpulmonary pressure, Ptp) was held constant during the periods of measurement. We found that intrapulmonary (upstream) venous pressures did not rise with elevation of left atrial (downstream) pressures at any Ptp until a pressure of at least 7 cmH2O above the base of the lung was exceeded. This left atrial pressure (below which a venous waterfall or flow-limiting segment effect was present) increased with Ptp when Ptp exceeded about 15 cmH2O. The waterfall occurs in the larger veins at the lung surface. Its presence and location suggest that intrapulmonary veins in the living animal are held open by the surrounding lung tissue and that neither the flow through them nor their contained volume is influenced by left atrial pressure when this is low.

Animals↗
PubMed1975

Cardiac limitation to maximal oxygen transport and changes in components after jogging across the US.

Observations were made before and 3-5 days after prolonged endurance jogging an average of 42 miles/day, 6 days/wk for 2.5 mo by a young male adult who voluntarily initiated a run across the United States. Both arterial PO2 and lactic acid increased. In each instance, the first limitation in circulatory delivery of oxygen was a plateau in stroke volume and cardiac output. Afterward, pulse deficit and systemic arterial pressure fell with exercise and heart rate accelerated. Although there was no change in oxygen transport (Q X CAO2), a reduction in stroke volume was exactly balanced by a rise in arterial oxygen content. Vital capacity, residual volume, and total lung capacity and diffusion capacity for carbon monoxide, hematocrit, and red cell mass increased, while plasma volume diminished and heart size and total blood volume were unchanged.

Adult↗
PubMed1975

Effects of pattern of ventilation on pulmonary metabolism and mechanics.

Effects of three patterns of mechanical ventilation on pulmonary mechanics, lung phospholipid and surface activity were studied in the normal closed-chest dog. The patterns were continuous mechanical ventilation with: 1) tidal volume (VT)=15 ml/kg; 2) VT=15 ml/kg with 10 cm H2O positive end-expiratory pressure (PEEP); 3) VT=50 ml/kg. THE DOGS IN EACH GROUP WERE VENTILATED FOR 24 HOURS, WITH CAREFUL ATTENTION PAID TO MAINTENANCE OF NORMAL BLOOD GASES, FLUID BALANCE, AND CARDIAC OUTPUT. The animals were sacrificed and the lungs studied to determine pressure-volume curves, dry lung weight/wet lung weight ratios, phospholpid contents and surface activities. The results were compared with control values in acutely sacrificed unventilated dogs. No significant change from controls was found with any pattern of ventilation employed with the exception of the tendency for lungs ventilated with PEEP to retain fluid (decreased dry lung weight/wet lung weight ratio).

Animals↗
PubMed1975

Diagnosis of neuroblastoma by electron microscopy of bone marrow aspirates.

Three patients are reported in whom the diagnosis of neuroblastoma was made following electron microscopy of a bone marrow aspirate. The ultrastructure of neuroblastoma cells is distinctive, and they can be distinguished by electron microscopy from cells of the other tumors with which neuroblastoma is often confused by light microscopy. The rapidity with which the diagnosis can be obtained through use of this procedure argues for its adoption in any patient in whom the diagnosis is suspected and who has tumor cells in bone marrow. Early initiation of appropriate therapy is made possible, and elaborate diagnostic procedures may be avoided.

Abdominal Neoplasms↗