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Biomedical subjects

J Butler

Publications and source records attributed to J Butler.

At least 109 records · Page 6Linked to original sources
PubMed1990

The proportion of glycosylated prolactin in serum is decreased in hyperprolactinemic states.

The proportion of serum PRL that is glycosylated has been determined, and the effects of physiological and pathological hyperprolactinaemia on this proportion have been examined. Glycosylated and nonglycosylated PRL were immunoprecipitated from serum and subjected to polyacrylamide gel electrophoresis under reducing and dissociating conditions. Separated proteins were then transferred to nitrocellulose paper by electroblotting and detected immunologically with anti-PRL antiserum and 125I-labeled protein-A, followed by autoradiography. The proportion of total monomeric PRL present in the glycosylated form was then estimated by densitometric scanning of autoradiograms. In normal individuals glycosylated PRL was predominant, accounting for about 72% of the circulating monomeric PRL. This proportion was markedly decreased (ranging from undetectable to about 60%) in the serum of women who were pregnant or were lactating postpartum and also in patients with hyperprolactinemia caused by a pituitary tumor. The results suggest that under basal conditions the majority of PRL secreted from the pituitary is glycosylated, but with physiological or pathological hyperprolactinemia the capacity for glycosylation is exceeded.

Adult↗
PubMed1990

Contrasting cytotoxic mechanisms of similar antitumour diaziridinylbenzoquinones.

The mechanisms of cytotoxicity of the antitumour diaziridinylbenzoquinones, AZQ and BZQ, have been investigated. HPLC analysis has been used to study the products as well as the rate of decomposition of acid-assisted ring-opening in aqueous medium as a function of pH. Microconcentrators with a molecular weight cutoff of 30 kDa were utilised to study the covalent binding of both compounds to calf thymus DNA. Radical production of both compounds in K562 cell incubations was followed using ESR and their uptake into K562 cells was monitored using radiolabelled compounds. The results show that these two diaziridinylbenzoquinones, although very similar in structure, have diverse mechanisms of cytotoxicity. The implications of these findings are discussed in the light of antitumor action.

Alkylating Agents↗
PubMed1990

Reflux pulmonary vein flow prevents pulmonary infarction after pulmonary artery obstruction.

Küttner showed in 1874 that simultaneous ligation of the pulmonary veins increased the frequency and severity of lung infarctions after pulmonary artery obstruction. The authors studied the possibility that a tidal pulmonary venous blood flow reflux from the left atrium could nourish the alveolar tissue. This could be driven by left atrial pressure transients and alternate expansion and compression of alveolar and extra alveolar vessels due to tidal lung volume changes. 5 anesthetized, closed chest goats were studied in the prone position after left pulmonary artery ligation and the obstruction of all bronchial blood flow to the left lung, checked by systemic microsphere injection. The inert, insoluble gas SF6 was infused into the left atrium and the exhaled gas from left and right lungs was collected separately. SF6 was found in the gas exhaled from the left lung, showing that left atrial blood had reached the alveolar tissues. The effective reflux blood flow was increased from control levels (no ventilation, normal left atrial pulses) by tidal volume changes, and by increased left atrial pressure transients (balloon induced mitral insufficiency). This venous reflux flow could explain why alveolar tissues do not suffer more severe injury when the pulmonary artery is obstructed.

Animals↗
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↗