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Biomedical subjects

J Butler

Publications and source records attributed to J Butler.

At least 163 records · Page 9Linked to original sources
PubMed1984

The repair of oxidized amino acids by antioxidants.

Natural and synthetic antioxidants have been shown to repair tryptophan radicals produced from the one-electron oxidation of the free tryptophan amino acid. It has also been observed that both tryptophan and tyrosine radicals in lysozyme can be repaired by these antioxidants to varying degrees of efficiency. Although SDS-solubilized alpha-tocopherol efficiently repairs free tryptophan radicals, it is very inefficient in repairing the amino acids in lysozyme. The rigidity and immobility of solubilized alpha-tocopherol can explain this lack of efficiency.

Antioxidants↗
PubMed1984

Influence of DNA binding on the formation and reactions of tryptophan and tyrosine radicals in peptides and proteins.

The rate constant of the one-electron oxidation of the tryptophan (Trp) or tyrosine (Tyr) residues by Br- X 2 radical anions is strongly decreased when the peptides are bound to DNA. Oxidation by N X 3 is much less affected by binding. These results can be explained by electrostatic repulsion between the charged polyphosphate backbone and the Br- X 2 radicals. Once oxidized, the interacting aromatic residues react with the DNA in a first order process with a rate constant of the order 10(3) s-1. These results have been extended to the single strand binding protein: the product of gene 32 of phage T4 (gp 32). The pulse radiolysis study suggests that one Trp residue of the protein oxidized by the Br- X 2 radicals reacts with the DNA in the complex while one Tyr residue is buried upon association. It is also shown that the exposure of Trp and Tyr residues to radical attack depends on whether the T4 SSB protein is bound to native or heat-denatured DNA.

DNA↗
PubMed1984

Coughs cause systemic blood flow.

Although it is known that rhythmic coughing can preserve consciousness during ventricular fibrillation, the arterial pressure transients which result have not yet been shown to reflect forward blood flow in man. The effectiveness of cough in causing forward flow in eight normal volunteers with bradycardia was studied. They coughed between cardiac cycles, using an audio and visual display of the electrocardiogram. The force of the cough was varied and measured with an oesophageal balloon. Blood flow was recorded with a Döppler velocity probe over the radial artery and a finger or ear photoplethysmograph. Motion artefact on the Döppler record due to coughing was excluded by transiently obstructing the brachial artery. We compared the areas under 5-10 consecutive Döppler and photoplethysmograph pulse flow tracings due to the cough and heart beat with those due to the immediately preceding heart beat alone. They were significantly increased. This augmentation was greater in those flow pulses accompanied by a more vigorous cough. It is concluded that coughing is associated with an effort dependent forward flow pulse in the arterial circulation.

Adult↗
PubMed1984

Acute increase in anastomotic bronchial blood flow after pulmonary arterial obstruction.

We examined the acute changes in anastomotic bronchial blood flow (Qbr) serially for the 1st h after pulmonary arterial obstruction and subsequent reperfusion. We isolated and perfused the pulmonary circulation of the otherwise intact left lower lobe (LLL) with autologous blood in the widely opened chest of anesthetized dogs. Qbr was measured from the amount of blood overflowing from the closed pulmonary vascular circuit and the changes in the lobe weight. The right lung and the test lobe (LLL) were ventilated independently. The LLL, which was in zone 2 (mean pulmonary arterial pressure = 14.8 cm H2O, pulmonary venous pressure = 0, alveolar pressure = 5-15 cmH2O), was weighed continuously. The systemic blood pressure, gases, and acid-base status were kept constant. In control dogs without pulmonary arterial obstruction, the Qbr did not change for 2 h. Five minutes after pulmonary arterial obstruction, there was already a marked increase in Qbr, which then continued to increase for 1 h. After reperfusion, Qbr decreased. The increase in Qbr was greater after complete lobar than sublobar pulmonary arterial obstruction. It was unaltered when the downstream pulmonary venous pressure was increased to match the preobstruction pulmonary microvascular pressure. Thus, in zone 2, reduction in downstream pressure was not responsible for the increase in Qbr; neither was the decrease in alveolar PCO2, since ventilating the lobe with 10% CO2 instead of air did not change the Qbr. These findings suggest that there is an acute increase in Qbr after pulmonary arterial obstruction and that is not due to downstream pressure or local PCO2 changes.

Animals↗
PubMed1984

The comparative toxicity of volcanic ash and quartz. Effects on cells derived from the human lung.

To evaluate the effects of volcanic ash and free crystalline silica on cells derived from the air space of the human lung, we compared the effects of these minerals on human alveolar macrophages and A549 cells, which are derived from human type II pneumocytes. The quartz was markedly cytotoxic to alveolar macrophages and A549 cells and stimulated the release of neutrophil chemotactic activity from alveolar macrophages. By contrast, volcanic ash was much less toxic to human alveolar macrophages and A549 cells and did not stimulate the release of neutrophil chemotactic activity from alveolar macrophages. The results with A549 cells were similar to findings with isolated type II pneumocytes recovered from rat lungs. Secretory IgA, IgG, and albumin, which are normally present in the air spaces of the lung, reduced the cytotoxicity of quartz in a dose-dependent manner. These results suggest that in the human lung quartz, but not volcanic ash, may cause direct damage to cells in the alveolar spaces and lead to the recruitment of phagocytes from the bloodstream to the lung.

Adult↗
PubMed1984

A lysosomal storage disorder in the BALB/c mouse: bone marrow transplantation.

The morphological and biochemical consequences of transplanting affected bone marrow from donor BALB/c mice with a lysosomal storage disorder (BALB/c LSD) into normal recipient mice were studied. Bone marrow was removed from normal BALB/c and BALB/c LSD mice and transfused into normal BALB/c recipient mice four hours after the mice received 850 rads of irradiation. Tissues of the recipient mice were examined 240 days later. This study revealed that the defective cells that constituted the visceral lesions of BALB/c LSD could be transplanted to normal BALB/c mice by the use of bone marrow from affected BALB/c LSD homozygote; that the defective cells of BALB/c LSD proliferated and disseminated throughout the mononuclear phagocytic system of the recipient; that there were increases in cholesterol, sphingolipids, and cystine with decreases in sphingomyelinase and glucocerebrosidase activity in tissues of the recipients; and that the recipients survived substantially longer than BALB/c LSD homozygotes and their lifespan was compromised mainly by the secondary effects of irradiation. These lesions, although not as extensive as in homozygous BALB/c LSD, paralleled the lesions which develop in BALB/c LSD. Since the recipient mice were not compromised by the short life span (70 days) of the BALB/c LSD mice, they may be used to study the long-term chronic effects of these metabolic lesions.

Animals↗
PubMed1984

Shortening of the first metatarsal as a complication of metatarsal osteotomies.

There have been few reports of shortening of the first ray of the foot because of damage to the physis of the first metatarsal during the performance of metatarsal osteotomy for residual metatarsus adductus. In a retrospective study of twenty-seven feet in twenty patients who underwent this procedure, eight feet in seven patients were noted to have some degree of residual shortening of the first ray. This is an incidence of 30 per cent. The follow-up period after osteotomy ranged from two years to seven years and four months (average, four years). We could find no clear correlation between the occurrence of shortening and the patient's age at osteotomy, sex, or race, or the etiology of the adduction for which the osteotomy had been done. A clear correlation was found, however, with the surgical technique that had been employed. In two of the eight feet with a short first ray, the osteotomy had been done within the physis of the first metatarsal. In the other feet the procedure had employed an osteotomy site close to the physis or extensive periosteal dissection, or both. The results in our patients implicate subperiosteal dissection of the first metatarsal as an important, previously unreported cause of damage to the physis and of the resultant shortening. We recommend radiographic determination of the relationship of the osteotomy site to the physis before dissection is performed.

Child↗
PubMed1983

Preferred sites for electron transfer between cytochrome c and iron and cobalt complexes.

The kinetics of oxidation of eight different singly substituted 4-carboxy-2,6-dinitrophenyl (CDNP) horse ferrocytochromes c, modified at lysine 7, 13, 25, 27, 60, 72, 86, or 87, and of one trinitrophenyl horse ferrocytochrome c, modified at lysine 13, by the 3- and 3+ inorganic complexes hexacyanoferrate(III) (Fe(CN)6(3-) ) and tris(1,10-phenanthroline)cobalt(III) (Co(phen)3(3+) ) have been characterized. The influence of the modified residues on the bimolecular rate constants for these reactions define the protein molecular surface involved. The site of electron exchange for both oxidants appears to be the solvent accessible edge of the heme prosthetic group or a closely related structure on the "front" surface of the molecule. The reaction with Fe(CN)6(3-) is most strongly influenced by modification of lysine 72, a residue to the left of the exposed heme edge. (CDNP lysine 72 cytochrome c yields a 3.6-fold decrease in the bimolecular rate constant, as compared to that for the native protein.) However, it is the region around lysine 27, to the right of the heme edge, that is most influential in the reaction with Co(phen)3(3+). (CDNP-lysine 27 cytochrome c exhibits a 7.3-fold increase in the rate constant, as compared to that for the native protein.) The kinetics of reaction of the CDNP-lysine 13, 60, 72, and 87 modified cytochromes c with Fe(CN)5(4-aminopyridine)2- as oxidant and Fe(CN)5(4-aminopyridine)3- and Fe(CN)5-(imidazole)3- as reductants have also been determined and further illustrate the influence of electrostatics on the kinetics of such protein-small molecule electron exchanges.

Chemical Phenomena↗
PubMed1983

Preoperative chemotherapy followed by mastectomy for locally advanced breast cancer.

Six patients with advanced local-regional breast cancer were reviewed. Five out of the six patients previously had had radiation therapy as part of the initial therapy. All patients had preoperative cycles of combination chemotherapy, either CMF or CAF. The two stage III patients had greater than 75% reduction in measurable tumor mass, which allowed a conventional modified radical or radical mastectomy to be performed. Both of these patients are now disease free at 26 and 27 months. The four stage IV patients had lesser operations following the chemotherapy (two simple mastectomies, one simple mastectomy plus axillary resection, and one axillary debulking). Reconstruction utilized advancement flaps in three patients and split-thickness skin grafts in the other. None of the patients had postoperative wound problems, and none of the patients had further problems with local cancer control. All patients had combination chemotherapy starting two to six weeks following surgery. Preoperative chemotherapy followed by surgery plays an important role in management of locally advanced stage III and stage IV breast cancer.

Adenocarcinoma↗
PubMed1983

Thermodynamic parameters associated with the binding of adrenalin and norephedrine to heparin.

Pulse radiolysis has been used to determine the thermodynamic parameters (delta G', delta H' and delta S') governing the binding of adrenalin and norephedrine to heparin. These complexes were completely dissociated by increasing concentrations of inorganic salts. Lower concentrations of divalent cations (e.g. Ca2+) than of monovalent cations (e.g. Na+) were necessary to effect dissociation of the complex. For each interaction an increase in drug binding occurred as the temperature was increased from ambient. However, a transition temperature was observed (48 degrees C) above which the drug was progressively released as the temperature was increased. These observations are discussed in terms of conformational changes induced in the polymer below and above its melting temperature.

Epinephrine↗
PubMed1983

A pulse radiolysis study of the interaction of ephedrine with carrageenans.

Pulse radiolysis has been used to determine the thermodynamic parameters (delta G', delta H' and delta S') governing the binding of ephedrine to three carrageenans. For each interaction an increase in drug binding occurred as the temperature was increased from ambient. However, a transition temperature was observed (49 degrees C) above which the drug was progressively released as the temperature was increased. These observations are discussed in terms of conformational changes induced in the polymers below and above their melting temperatures.

Carrageenan↗
PubMed1983

Phenol coupling initiated by one-electron oxidation of tyrosine units in peptides and histone.

Phenoxyl radicals generated pulse radiolytically by the reaction of N.3 with Gly-Tyr decay biomolecularly (2k = 4.7 X 10(8)M-1 s-1) with efficient formation of 2,2'-dimers, which enolize rapidly (k = 2.7 X 10(4) s-1) to produce the 2,2'-biphenolic product. The build-up of the characteristic 2,2'-biphenol fluorescence (400 nm) and absorption also indicated a delayed (k = 80 s-1) process, probably involving the phenoxyl <-> phenoxy-quinol equilibrium. About 60 per cent of the Gly-Tyr phenoxyls were found to dimerize to the 2,2'-biphenol, and a similarly efficient 2,2'-coupling seems to occur with other tyrosyls, such as Lys-Tyr-Lys and histone. gamma-Radiolysis was applied to estimate relative yields of formation of 2,2'-biphenols under various conditions. Dimerization is almost completely inhibited by cysteine or oxygen, consistent with phenoxyl 'repair' by cysteine or O-.2; disproportionation of O-.2 with SOD prevents repair. The phenol 2,2'-coupling is less efficient for .OH- and inefficient for e-aq-initiation.

Dipeptides↗
PubMed1983

Investigation of a possible role for superoxide anion production in tumour promotion.

The effect of the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) on superoxide (O-.2) production and superoxide dismutase (SOD) levels has been investigated in human leukocytes and human and rodent fibroblast cell lines. Both O-.2 production and a lowering of the SOD levels were observed in the human leukocytes, but these changes could not be correlated with the induction of gross chromosomal aberrations by TPA. Similarly the use of an O-.2-generating system failed to induce chromosome aberrations. However, a small percentage increase in chromosome aberrations was observed in human fibroblasts after repeated and prolonged exposure to TPA. TPA was shown to reduce the SOD levels in these cells. Overall however, the data suggest that the chromosomes are not the primary site of action for the superoxide anions produced by TPA.

Animals↗
PubMed1983

Beta-adrenoceptor adaptation to acute exercise.

The effects of strenuous exercise on lymphocyte beta-adrenoceptor density and responsiveness in nine men were biphasic. There was an initial increase in receptor density, seen immediately after exercise, with a subsequent decline to below pre-exercise values. In parallel, maximum isoprenaline-stimulated cyclic AMP production by lymphocytes was greatly increased at the end of exercise and decreased thereafter. The increases seen at the end of exercise may be of functional significance and may represent a response of the tissue to the demands placed upon it. After a time, however, a desensitization process takes over, possibly with a protective role.

Adaptation, Physiological↗
PubMed1983

Extra-alveolar vessel contribution to hydrostatic pulmonary edema in in situ dog lungs.

We determined the relative contribution of larger extra-alveolar arteries and veins to hydrostatic edema in in situ dog lungs. Left lower lobe alveolar and vascular pressures were controlled in 24 open-chest, anesthetized, heparinized dogs. Zero pressure was at the lobe base. Normal blood gases were maintained by ventilating the right lung. The left lower lobe was inflated with 5% CO2 and air to an alveolar pressure of 10 or 25 cmH2O and suspended from a strain gauge, which allowed continual weight recording. Vascular pressures were raised to alveolar pressure plus lung height (zone III) before and after pulmonary arterial or venous embolization with 37- to 74-microns polystyrene beads, which isolated the larger extra-alveolar arteries or veins from alveolar vessels. The weight change occurring during the last 3 min of the 5-min hydrostatic stress was taken to represent transvascular fluid flux. At an alveolar pressure of 25 cmH2O (estimated transmural pressure 40 cmH2O), leakage from the larger extra-alveolar arteries and veins accounted for 41 and 32%, respectively, of the total transvascular fluid flux occurring after embolization. At an alveolar pressure of 10 cmH2O (estimated transmural pressure 22 cmH2O), no extra-alveolar vessel leakage occurred. However, when vascular pressures were raised to provide a transmural pressure similar to that present at the higher alveolar pressure, the same contribution from larger extra-alveolar vessels was observed.

Animals↗
PubMed1983

Citric acid airway constriction in dogs with hyperreactive airways.

To understand the mechanisms underlying the bronchoconstrictor response to 10% citric acid administered for 5 min in Basenji-Greyhound (BG) dogs, we evaluated the protection afforded by atropine (0.2 and 0.4 mg/kg iv) and by aerosols of isoproterenol (1 mg/ml) and cromolyn sodium (20 mg/ml). In untreated dogs, citric acid increased pulmonary resistance by 4.6- to 11.5-fold and decreased dynamic compliance (Cdyn) to 45-55% of the control response. Isoproterenol and cromolyn sodium significantly reduced the response, whereas atropine did not. Moreover we have demonstrated in the arterial plasma of these dogs a slow-reacting substance (SRS) after, but not before, citric acid challenge. This SRS exhibits both pharmacologic properties and chemical characteristics similar to leukotrienes. We conclude that mediators of immediate-type hypersensitivity rather than reflex mechanisms play a dominant role in the production of airway constriction during citric acid (5-min) challenge in BG dogs.

Airway Resistance↗