PubMed Health⌕ Search

Biomedical subjects

J Butler

Publications and source records attributed to J Butler.

At least 145 records · Page 8Linked to original sources
PubMed1989

Apparent inactivation of alpha 1-antiproteinase by sulphur-containing radicals derived from penicillamine.

alpha 1-Antiproteinase is the major inhibitor of proteolytic enzymes, such as elastase, in human plasma. Its elastase-inhibitory capacity can be inactivated by exposure to hydroxyl radicals (.OH) generated either by pulse radiolysis or by an Fe3+-EDTA/H2O2/ascorbic acid system. Inactivation of alpha 1-antiproteinase by radiolytically-generated .OH under anoxic conditions was decreased by adding a range of anti-inflammatory drugs to the reaction mixtures, including the thiol compound penicillamine. However, under conditions favouring formation of oxysulphur radicals, protection by thiols such as penicillamine was much decreased. It is proposed that sulphur-containing radicals resulting from attack of biologically-produced oxidants upon penicillamine in the presence of O2 can themselves inactivate alpha 1-antiproteinase, and that such radicals might contribute to the side-effects produced by penicillamine or gold thiol therapy in rheumatoid arthritis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1989

The alkylation of DNA in vitro by 2,5-bis(2-hydroxyethylamino)-3,6-diaziridinyl-1,4-benzoquinone (BZQ)--I.

Cell toxicity by BZQ could not be explained by free radical formation and thus further work has been undertaken to elucidate a possible mechanism of cell killing. By using radiolabelled BZQ, in vitro DNA-drug binding has been investigated. The effect of salt, buffer and drug concentrations was determined in the pH range 4.0 to 8.0. The influence of in situ oxidation and reduction on BZQ binding was also studied as a function of pH. In an effort to ascertain any base specificity of BZQ binding the homopolymers, Poly[dG]. Poly[dC] and Poly[dA]. Poly[dT] were treated with radiolabelled BZQ in the pH range 4.0 to 8.0. A fluorescence assay was used to demonstrate the possible involvement of DNA cross-linking in cellular activity. From this work, it was concluded that BZQ functions as a bifunctional alkylating agent by an acid-assisted aziridine ring-opening mechanism and that other factors including oxidation or reduction are much less important.

Alkylating Agents↗
PubMed1989

Contextual gating of memory retrieval.

In two experiments, 3-month-old infants learned to move a crib mobile (the cue) in the presence of a distinctive crib bumper (the context) by operant kicking. In Experiment 1A, infants were trained for 2 days and tested either 1, 3, or 5 days later with one of four same/different cue/context combinations. After all delays, infants tested with the original cue and context exhibited excellent retention, and those tested with a different cue and context exhibited none. Changing the context but not the cue disrupted retention after 3 and 5 days but not after 1 day; in contrast, changing the cue but not the context disrupted retention after all delays. In Experiment 1B, the failure of a contextual change to impair retention after 1 day was replicated. In Experiment 2, three same/different cue/context combinations were used as reminders in a reactivation paradigm, and all infants were tested 1 day later with their original training combination. A change in either the context or the cue significantly impaired the effectiveness of the reminder. These results reveal not only that contextual information is incorporated into the memory representations of very immature infants but also that memory retrieval is highly specific to the context in which an event was originally encoded. This specificity buffers against generalized memory retrieval after long retention intervals. The data are consistent with Reeves and Sperling's 1986 model of attention-gating. The context appears to serve as the initial gate for attention to potentially effective retrieval cues.

Analysis of Variance↗
PubMed1989

The antioxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid.

N-acetylcysteine has been widely used as an antioxidant in vivo and in vitro. Its reaction with four oxidant species has therefore been examined. N-acetylcysteine is a powerful scavenger of hypochlorous acid (H--OCl); low concentrations are able to protect alpha 1-antiproteinase against inactivation by HOCl. N-acetylcysteine also reacts with hydroxyl radical with a rate constant of 1.36 X 10(10) M-1s-1, as determined by pulse radiolysis. It also reacts slowly with H2O2, but no reaction of N-acetylcysteine with superoxide (O2-) could be detected within the limits of our assay procedures.

Acetylcysteine↗
PubMed1989

The role of sulphur peptide functions in free radical transfer: a pulse radiolysis study.

Cascading transfers of free radical centres, involving sulphur and aromatic protein functions, have been studied in further detail. The disulphide radical anion appears to be an important terminus of both oxidative and reductive radical transfer. In deaerated solutions of cysteine (20 mmol dm-3) the yield of Cys2/SS.- closely resembles the yield of all primary free radicals generated by water radiolysis (.OH, H. and eaq-). The alanyl Ala/C beta., formed by electron addition to cysteine and subsequent SH- elimination, oxidizes cysteine with a rate constant of k8 = 5.0 x 10(6)dm3mol-1s-1 at pH 6 to 7 and 3.6 x 10(6)dm3mol-1s-1 at pH 9 to 10. In the case of glutathione (GSH) the eaq--induced carbon-centred radical oxidizes the parent thiol with rate constants k(G. + GSH) of 7.0 x 10(6) and 1.3 x 10(6)dm3mol-1s-1 at pH 8 and pH 10, respectively; and with dithiothreitol (D(SH)2) the corresponding reaction rate is k(.DSH + D(SH)2) = 5.5 x 10(6)dm3mol-1s-1 at pH 7.0. The decarboxylated methionyl Met/C. alpha, formed by reaction of .OH with methionine, is capable of electron transfer to cystine, indicating a reduction potential for decarboxylated methione more negative than -1.6 V. The ring-closed methionyl radical cation Met/SN.+, formed by reaction of .OH with Met-Gly, oxidizes azide via equilibration, Met/SN.+ + H+ + N3- in equilibrium Met + N3., which enables an estimate to be given for the one-electron reduction potential: E degrees (Met/SN.+ + H+; Met) = +1.42 +/- 0.3 V (pH 6.8). Some further reactions of oxidizing dimeric Met2/SS.+ species in neutral solution have been demonstrated. The direction and nature of the transfers can be expressed by the scheme: (formula; see text).

Chemical Phenomena↗
PubMed1989

Dynamic response of human cervical spine ligaments.

This study was undertaken to investigate the dynamic response of human cervical spine ligaments. Uniaxial tensile failure tests were conducted on anterior longitudinal ligament (AL) and ligamentum flavum (LF) structures. These ligaments were tested under in situ conditions by transecting all the elements except the one (AL or LF) under study. A fixture was designed to properly align the specimen to induce a uniaxial mode of loading. A six-axis load cell was placed at the distal end of the specimen. The proximal end of the specimen was attached to the piston of a specially designed electrohydraulic testing device. The biomechanical properties of the ligaments were determined at four different loading rates of 8.89, 25.0, 250.0 and 2500 mm/sec. The mechanical response indicated nonlinear and sigmoidal characteristics. The ultimate tensile failure load, stiffness, and energy-absorbing capacity at failure were found to increase with increasing loading rates for both the AL and LF. However, the distractions at failure did not indicate this tendency. While the ultimate tensile force and ultimate energy-absorbing capacity varied nonlinearly with the logarithm of the loading rate, the stiffness varied linearly.

Aged↗
PubMed1989

Mechanics of the respiratory system during high frequency ventilation.

No rational approach has evolved for selecting operating conditions for clinical application of high-frequency ventilation (HFV). To this end, we divide our discussion of HFV into considerations of mechanics versus transport, and treat the latter as a constraint. After describing some of the phenomena that influence distending pressure (and its distribution) expressed across pulmonary tissues, we address the pressure costs per unit ventilation and the factors that influence them. This narrowly defined approach leads to some fundamental strategies, compromises, and dilemmas. In particular, consideration of the mechanical interaction of the lung and chest wall leads to a paradox, and points out that the influence of the chest wall upon phasic regional lung distension is not well understood.

Animals↗
PubMed1989

Pulmonary vascular resistance rises with lung volume on exercise in obstructed airflow disease.

There has been experimental evidence that lung distension produces an increase in pulmonary vascular resistance (PVR). To study this effect in patients, we measured functional residual capacity (FRC) by helium dilution at rest and during low-load supine exercise in 30 patients with chronic obstructive pulmonary disease. Pulmonary haemodynamics were studied in these patients under the same conditions. FRC increased from rest (4.32 +/- 0.21 l) to exercise (4.71 +/- 0.20, P less than 0.001) but the change was smaller in the patients with the highest FRC at rest: there was a significant negative correlation between FRC change and FRC at rest (r = -0.38, P less than 0.01). There were seven patients with a small FRC change (less than 0.2 l) with exercise and 10 patients with a marked increase (greater than 0.5 l). Exercise was of the same load on average. FRC at rest was 5.1 l in the first group and 4 l in the second (P less than 0.05). Blood gases were almost identical at rest, and almost unchanged during exercise. PVR decreased from rest to exercise by 33 dyn.s.cm-5 in the first group and increased by 24 in the second (P less than 0.01). There was a significant correlation (P less than 0.05) between PVR and FRC changes from rest to exercise. These results suggest that lung distension may play a role in the PVR increase seen in some COPD patients with exercise.

Exercise↗
PubMed1989

Hypogonadism and sexual dysfunction in hemochromatosis: the effects of cirrhosis and diabetes.

The contribution of diabetes and cirrhosis to sexual dysfunction and hypogonadism was evaluated by two-way analysis of variance in a group of 30 men with idiopathic hemochromatosis. The prevalence of severe sexual dysfunction was significantly higher in men with hemochromatosis than in a control group matched for prevalence of diabetes and age (P less than 0.001). In both controls and hemochromatosis patients the presence of diabetes was significantly associated with sexual dysfunction (P less than 0.005), but the more severe symptoms in the hemochromatosis patients were related to the additive effects of hypoandrogenism (P less than 0.01). Sexual dysfunction was a common early complaint in hemochromatosis patients, but these symptoms were frequently overlooked, leading to diagnostic delay. Mean testicular volume was a useful measure of gonadal status, being significantly correlated with indices of serum free testosterone (rs = 0.83; P less than 0.01) and LH (rs = 0.71; P less than 0.001). The presence of cirrhosis did not contribute significantly to symptomatology, but had an effect independent of and additive to hypogonadotropic hypogonadism in reducing serum free testosterone (P less than 0.02) and estradiol (P less than 0.002), an effect apparently mediated through central rather than testicular mechanisms. Hypoandrogenism was associated with an increase in serum sex hormone-binding globulin (SHBG) concentrations (P less than 0.005), but cirrhosis also had an independent effect in raising SHBG (P less than 0.005), which could not be accounted for by changes in circulating sex hormone concentrations. Thus, the evaluation of sexual dysfunction or hypogonadism in men with hemochromatosis requires consideration of the effects of both diabetes and cirrhosis. Because of the greater variance in SHBG some estimate of free testosterone rather than total testosterone is preferable.

Adult↗
PubMed1989

Serum prolactin in uraemia: correlations between bioactivity and activity in two immunoassays.

The clinical significance of hyperprolactinaemia in uraemic patients is uncertain and discrepancies between immunoactivity and biological activity of serum hPRL have been reported. We have modified the Nb2 cell bioassay to improve specificity for hPRL and used this assay to measure hPRL bioactivity in sera from 26 uraemic patients and 40 control subjects. Seventeen patients were receiving regular haemodialysis and 9 continuous ambulatory peritoneal dialysis. Levels of hPRL bioactivity were compared with hPRL immunoactivity measured by RIA (PRL-RIA) and by immunoradiometric assay (PRL-IRMA). Serum hPRL levels measured by all three assays were significantly elevated in uraemic patients compared with control subjects (P less than 0.001). The immunoradiometric method gave significantly lower results than RIA in control subjects but not in uraemic patients (P less than 0.05). There was no significant difference in mean ratio of hPRL bioactivity to PRL-RIA between patients and control subjects (1.18 +/- 0.05 vs 1.11 +/- 0.03, mean +/- SEM). The ratio of hPRL bioactivity to PRL-IRMA was slightly decreased in uraemic patients compared with controls (P = 0.05). Serum hPRL bioactivity was closely correlated with immunoactivity in both immunoassays (r greater than or equal to 0.96) in patients and controls. These results confirm that elevated serum hPRL levels in uraemic patients represent biologically active hormone which may contribute to hypogonadism.

Adult↗
PubMed1988

The antioxidant action of taurine, hypotaurine and their metabolic precursors.

It has been suggested that taurine, hypotaurine and their metabolic precursors (cysteic acid, cysteamine and cysteinesulphinic acid) might act as antioxidants in vivo. The rates of their reactions with the biologically important oxidants hydroxyl radical (.OH), superoxide radical (O2.-), hydrogen peroxide (H2O2) and hypochlorous acid (HOCl) were studied. Their ability to inhibit iron-ion-dependent formation of .OH from H2O2 by chelating iron ions was also tested. Taurine does not react rapidly with O2.-, H2O2 or .OH, and the product of its reaction with HOCl is still sufficiently oxidizing to inactivate alpha 1-antiproteinase. Thus it seems unlikely that taurine functions as an antioxidant in vivo. Cysteic acid is also poorly reactive to the above oxidizing species. By contrast, hypotaurine is an excellent scavenger of .OH and HOCl and can interfere with iron-ion-dependent formation of .OH, although no reaction with O2.- or H2O2 could be detected within the limits of our assay techniques. Cysteamine is an excellent scavenger of .OH and HOCl; it also reacts with H2O2, but no reaction with O2.- could be measured within the limits of our assay techniques. It is concluded that cysteamine and hypotaurine are far more likely to act as antioxidants in vivo than is taurine, provided that they are present in sufficient concentration at sites of oxidant generation.

Antioxidants↗
PubMed1988

The lack of correlation between toxicity and free radical formation of two diaziridinyl benzoquinones.

L1210 and K562 leukaemic cells have been used to study the relationship between cytotoxicity and free radical production by two aziridinyl benzoquinones, 2,5-bis(carboethoxyamino)3,6-diaziridinyl-1,4-benzoquinone (AZQ) and 2,5-bis(2-hydroxyethylamino)-3,6-diaziridinyl-1,4-benzoquinone (BZQ). BZQ showed a high level of toxicity in both cell lines, but no ESR signal was detectable, while AZQ readily produced an ESR signal but much lower cytotoxicity was observed, particularly in L1210 cells. The rate of superoxide formation was measured for each drug. The results demonstrate that cell killing and free radical production do not necessarily concur.

Antineoplastic Agents↗
PubMed1988

Reductive activation of mitomycin C.

Mitomycin C, an antitumor antibiotic, is known to require reductive activation in order to function as an alkylating agent. In this work reduction has been carried out by using radiolytically produced formate radicals that reduce mitomycin C to its semiquinone in a clean rapid one-electron reaction. The ultimate products of the reduction are cis- and trans-2,7-diamino-1-hydroxymitosene (B1 and B2) and 2,7-diaminomitosene (C). The yields of these compounds were found to be the same when the rate of reduction was varied by 11 orders of magnitude. At pH 7, one mitosene molecule is formed for every two formate radicals, while at pH 9.1, about eight mitosene molecules are formed per formate radical. The ratio of (B1 + B2)/C is less than 0.4 at pH 5.7, 1.0 at pH 7, and greater than 3.5 at pH 9.1. Observations have been made of changes in optical absorption due to the formation of the semiquinone and hydroquinone of both mitomycin C itself and 2,7-diamino-1-hydroxymitosene (B). The direct conversion of the semiquinone form of mitomycin C into the semiquinone of B proceeds slowly, if at all. The semiquinone form of B will rapidly reduce mitomycin C (k = 7.2 X 10(8) M-1 s-1). The hydroquinone of mitomycin C undergoes changes resulting in the formation of B and C. The yields of B and C depend on pH.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗
PubMed1988

The chronic effects of desipramine and sertraline on platelet and synaptosomal 5HT uptake in olfactory bulbectomised rats.

1. Depressed patients show a characteristic decrease in the rate of uptake of serotonin into their platelets, which is normalised only by clinically effective antidepressant treatment. 2. We also find a decrease in platelet 5HT uptake rates in the olfactory bulbectomised (OB) rat model of depression, which return to normal following three weeks of treatment with desipramine or sertraline. 3. Synaptosomal 5HT uptake appears to consist of a low affinity, high capacity component and a high affinity, low capacity component, both of which are increased in the OB rat, compared to its sham operated control, and normalised by chronic antidepressant treatment. 4. The low affinity uptake of serotonin is not inhibited by in vitro incubation with sertraline, which suggests that the low affinity system may be associated with a non-specific uptake of 5HT into noradrenergic or dopaminergic nerve endings.

1-Naphthylamine↗
PubMed1988

The platelet serotonergic system in depression and following sertraline treatment.

This preliminary study examined the effect of 8 weeks' treatment with the serotonin (5HT) uptake inhibitor, sertraline, on the platelet serotonergic system in depression. Patient pre-treatment platelet 5HT uptake rates and 5HT-mediated platelet aggregation responses were significantly reduced compared to the control values. Binding of the tritiated 5HT2 receptor antagonist, 3H-ketanserin, to platelet membranes from the patient group was increased above control levels. All the patients in the study had recovered from the depressive episode, assessed using the Hamilton depression rating scale, following 8 weeks' sertraline treatment. Eight weeks' sertraline treatment also resulted in a normalization of the biochemical parameters examined. Therefore, we conclude that sertraline is an effective antidepressant and these results confirm previous reports of abnormal platelet serotonin transport and aggregation response as putative markers of the depressed state.

1-Naphthylamine↗
PubMed1988

Neuroendocrine-gonadal axis in men: frequent sampling of LH, FSH, and testosterone.

Previous studies of episodic hormone secretion of the hypothalamic-pituitary-gonadal axis in normal men have produced conflicting results due to examinations of small cohorts of subjects or to limited sampling techniques. We evaluated gonadotropin and testosterone (T) secretory patterns in 20 normal men by sampling blood at 10-min intervals for luteinizing hormone (LH) and follicle-stimulating hormone (FSH). T concentrations were also analyzed at 20-min intervals in 10 subjects. A previously unappreciated spectrum of gonadotropin and T secretory patterns was observed in normal men. Both mean LH concentrations and mean LH pulse amplitudes varied fourfold between individuals. LH interpulse intervals varied from 30 to 480 min (mean 119 +/- 32). Results also suggested a relative refractory period at the level of the hypothalamus or pituitary. In three subjects, a striking nighttime accentuation of LH pulsations was noted. Through use of Fourier analysis, a diurnal variation in LH was observed in the population (P less than 0.02). Mean FSH levels showed marked variation between individual subjects, with discrete pulses rarely observed. No diurnal variation in FSH secretion was noted. Serum T concentrations determined at 6-h intervals ranged from 105 to 1,316 ng/dl between subjects. When T was measured at 20-min intervals, marked intermittent declines in the T concentrations to levels well below the normal range were observed in 3 of 10 subjects. T secretion was found to lag behind LH secretion by approximately 40 min (P less than 0.02).

Adult↗
PubMed1988

Cause of the raised wedge pressure on exercise in chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) markedly increase their pulmonary artery wedge pressure on mild exercise even though they have no overt left heart disease and no increase in the esophageal pressure (as a reflection of mean intrathoracic pressure). We wondered if lung distension due to gas trapping during the hyperpnea of exercise might cause the wedge pressure to rise by increasing juxtacardiac pressures above esophageal pressures. If this were so, then (1) tachypnea alone, without exercise, should cause the FRC and intracardiac pressures to increase in patients with COPD, (2) there should be an increase in FRC associated with the rise in wedge pressure on exercise, and (3) these changes should not occur in patients without COPD. We studied 39 patients with COPD (Ppa = 21 +/- 6 mm Hg [mean +/- SD], FEV1 [% predicted] = 39 +/- 16) and 13 control patients with similar pulmonary artery pressures but no airflow obstruction (Ppa = 22 +/- 20 mm Hg, FEV1 [% predicted] = 110 +/- 24). In those with COPD, light exercise raised the FRC by 0.5 +/- 0.5 L. Tachypnea alone, at the rate present during exercise, raised the FRC by 0.6 +/- 0.4 L and there was a 10% increase in left lower lobe area on lateral chest X-ray. Wedge, right atrial, and pulmonary artery pressures rose together during tachypnea with and without exercise. By contrast, in the control patients without COPD, the right atrial pressure change on exercise did not reflect that of the left atrium in extent or direction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗