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Biomedical subjects

M Butler

Publications and source records attributed to M Butler.

At least 19 recordsLinked to original sources
PubMed1992

Reducing sugars can induce the oxidative inactivation of rhodanese.

The enzyme rhodanese (thiosulfate sulfurtransferase, EC 2.8.1.1) is inactivated on incubation with reducing sugars such as glucose, mannose, or fructose, but is stable with non-reducing sugars or related polyhydroxy compounds. The enzyme is inactivated with (ES) or without (E) the transferable sulfur atom, although E is considerably more sensitive, and inactivation is accentuated by cyanide. Inactivation of E is accompanied by increased proteolytic susceptibility, a decreased sulfhydryl titer, a red-shift and quenching of the protein fluorescence, and the appearance of hydrophobic surfaces. Superoxide dismutase and/or catalase protect rhodanese. Inactive enzyme can be partially reactivated during assay and almost completely reactivated by incubation with thiosulfate, lauryl maltoside, and 2-mercaptoethanol. These results are similar to those observed when rhodanese is inactivated by hydrogen peroxide. These observations, as well as the cyanide-dependent, oxidative inactivation by phenylglyoxal, are explained by invoking the formation of reactive oxygen species such as superoxide or hydrogen peroxide from autooxidation of alpha-hydroxy carbonyl compounds, which can be facilitated by cyanide.

Fructose↗
PubMed1992

Neuropsychological battery choice and theoretical orientation: a multivariate analysis.

In order to investigate the tests selected by neuropsychologists to make up clinical batteries, a large survey of neuropsychological test usage was cluster analyzed. This provided groupings of tests that are endorsed in common. Theoretical orientation within neuropsychology also was included in the analysis to determine which tests and clusters of tests are more and less associated with the reported orientation of the neuropsychologist. Fifteen clusters of tests were found. Strong and appropriate associations with the eclectic, hypothesis testing, process approach, Halstead-Reitan, Luria, and Benton orientations were seen.

Attitude of Health Personnel↗
PubMed1992

Characterization of glutamine metabolism in two related murine hybridomas.

Aspects of glutamine metabolism were examined in two related hybridomas, a high-producing line (PQX B1/2) and a low-producing line (PQX B2/2). The growth and metabolic characteristics of both cell lines were identical or very similar. During batch growth glutamine was completely exhausted from the medium and an examination of the fate of [14C]glutamine highlighted the importance of this amino acid as an energy source. The relative enzyme activities and the amount of ammonia produced during growth indicated that glutamine is oxidized preferentially via the transamination pathway. The overall rate of glutamine utilization from the growth medium was similar to the rate of [14C]glutamine uptake which suggests that transport may regulate glutamine metabolism.

Animals↗
PubMed1992

Endomysial antibody: is it the best screening test for coeliac disease?

The sensitivities and specificities of the IgA and IgG antigliadin antibody and the IgA antireticulin antibody have been compared with the recently described endomysial antibody directed against the basement membrane of smooth muscle in monkey oesophagus. One hundred and seventeen patients with adult coeliac disease (21 untreated), 84 patients with inflammatory bowel disease, systemic lupus erythematosus and rheumatoid arthritis (comprising the disease control group), 47 normal controls and a miscellaneous group of 29 patients, who were selected because of a positive reticulin staining pattern, were investigated. These results were correlated with the degree of abnormality of the intestinal mucosa in patients with adult coeliac disease. Endomysial antibodies were found in all patients with untreated coeliac disease and subtotal villous atrophy and in 47% of patients on a non-strict gluten free diet. One patient on a strict gluten free diet was positive and had partial villous atrophy while all patients in disease control groups were negative. Results were variable with the antireticulin and antigliadin antibodies. Sensitivity and correlation with subtotal villous atrophy in the untreated patients was 100%. It is concluded that the endomysial antibody is superior to other current antibody tests and should be used in preference for the diagnosis of coeliac disease.

Adolescent↗
PubMed1991

A critical analysis of the use of sialic acid determination in the diagnosis of malignancy.

The measurement of serum sialic acid in sera from individuals with leukemia, breast, gastrointestinal, lung and bladder cancers, brucellosis and manic depression is described. The serum sialic acid levels were also examined in mice bearing Landschutz ascites tumours. The presence of sialic acid-enriched glycopeptides in serum was shown. The results indicate that while sialic acid may be significantly elevated in sera of some tumour-bearing individuals, it is not solely tumour-derived. Its application as a tumour marker is limited and requires critical analysis.

Animals↗
PubMed1991

Growth inhibition in animal cell culture. The effect of lactate and ammonia.

Eight independent cell lines accumulated ammonia in culture to concentrations between 1.3 and 2.9 mM. The growth inhibition of such concentrations of ammonium chloride when added to culture medium was variable. The cell lines tested could be divided into 3 groups depending on their growth response to 2 mM added NH4Cl. In the first group (293, HDF, Vero, and PQXB1/2) little (less than 14%) or no growth inhibition occurred. In the second group (McCoy and MDCK) a reduction in final cell yield of 50-60% was observed. The third group (HeLa and BHK) was most sensitive to the effects of NH4Cl with growth inhibition (greater than 75%) compared to controls. The growth inhibitory effect of added lactate up to 20 mM was negligible (less than 10%) for 3 cell lines, although one cell line (PQXB1/2) showed greater sensitivity. The interactive effects of ammonia and lactate were determined in a matrix experiment. At lactate (greater than 12 mM) and ammonia (1-4 mM), the growth inhibitory effects of the two components were synergistic. However, at low concentrations of lactate (less than 12 mM) the toxic effect of ammonia was reduced. A proposed mechanism for the sparing effect of lactate on ammonia toxicity is discussed. This may have importance in developing strategies for the optimal growth of ammonia-sensitive cell lines.

Ammonia↗
PubMed1991

Granisetron, a selective 5-HT3 receptor antagonist, for the prevention of radiation induced emesis during total body irradiation.

The antiemetic efficacy of granisetron was tested in an open trial in patients undergoing highly emetogenic treatment by single fraction total body irradiation. Thirty-two consecutive patients were entered. Results were both patient- and observer-rated. Following a single intravenous dose of granisetron 18 patients (56.3%) experienced total protection and a further 13 (40.6%) had major antiemetic protection with four of these patients experiencing nausea only. One patient experienced an anaphylactic reaction on infusion of monoclonal antibody-treated donor marrow 5 h after administration of the trial drug and vomited on multiple occasions. The reaction was associated with hypotension. A further patient experienced transient hypotension secondary to septicaemia 8 h after receiving granisetron. Three patients required a second dose. Headache was the most frequent side-effect occurring in three patients, but in to of these patients the test drug was not thought to be implicated. In conclusion granisetron is a highly effective agent in controlling radiation induced emesis with a favourable toxicity profile.

Adolescent↗
PubMed1990

(Difluoromethylene)phosphates of guanine nucleosides as probes of DNA polymerases and G proteins.

5'-Polyphosphates of N2-(p-n-butylphenyl)-2'-deoxyguanosine and -guanosine which contain a difluoromethylene group in place of a phosphoanhydride oxygen have been synthesized. 5'-[beta,gamma-(Difluoromethylene)triphosphates], including that of 2'-deoxyguanosine, were prepared by reaction of the corresponding 5'-phosphates, activated by 1,1'-carbonyldiimidazole, with difluoromethanediphosphonate. The 5'-[(difluoromethylene)diphosphate] of N2-(p-n-butylphenyl)guanosine was prepared by treatment of a protected 5'-tosyl nucleoside with difluoromethanediphosphonate, followed by deprotection. Condensation of this nucleotide, activated with 1,1'-carbonyldiimidazole, with orthophosphate gave N2-(p-n-butylphenyl)guanosine 5'-[(alpha,beta-difluoromethylene)triphosphate]. Products were characterized by 31P and 19F NMR spectroscopy. The phosphonates were tested for their ability to displace [3H]GDP from the GTP binding proteins cellular (EC) and oncogenic (Leu-61) Ha-ras p21, and for their ability to inhibit DNA polymerase alpha from Chinese hamster ovary cells. The p21s bound weakly to a triphosphonate when the CF2 group was in the beta,gamma position, but not when it was in the alpha,beta position, and they did not bind to the corresponding (difluoromethylene)diphosphate. In contrast, the CF2 group had no effect on inhibition of DNA polymerase alpha by N2-(p-n-butylphenyl)-2'-deoxyguanosine 5'-[(beta,gamma-difluoromethylene)triphospate]. 2'-Deoxyguanosine 5'-[(beta,gamma-difluoromethylene)triphosphate] was found to be a bona fide substrate for several DNA polymerases and had a lower apparent Km than dGTP with Bacillus subtilis DNA polymerase III.

Bacillus subtilis↗
PubMed1990

The effect of pH on the toxicity of ammonia to a murine hybridoma.

The growth inhibition of a murine hybridoma mediated by ammonium chloride was shown to vary with the pH of the culture medium. Values for the initial media concentration causing 50% growth inhibition (IC50) ranged from 4 mM to 7.6 mM as the pH was reduced from 7.8 to 6.8. A significant negative correlation was observed between the IC50 and the NH3 concentration of the medium, suggesting that ammonia and not ammonium may be the toxic species in the culture medium. The optimum initial pH for cell growth was 7.4. However, this optimum shifts to lower pH as ammonia accumulates in culture as a metabolic by-product. This suggests that in order to obtain high cell yields, it may be beneficial to adopt a culture strategy of lowering pH during cell growth to offset the inhibitory effects of accumulated ammonia.

Ammonia↗
PubMed1990

Adaptation to non-ammoniagenic medium and selective substrate feeding lead to enhanced yields in animal cell cultures.

Methods for the adaptation of three animal cell lines to media in which glutamine is replaced with either glutamate or 2-oxoglutarate are described. The cell lines differ in their rate of adaptation. The consequences of the adaptation of the McCoy cell line to a glutamate-based medium was measured in terms of: cell yield (increased by 17%), ammonia accumulation (reduced by 70%), glucose consumption (decreased by greater than 70%) and lactate accumulation (decreased by greater than 75%). The value of such adaptation and concomitant changes in energy metabolism lies in the potential for increased cell yields. Batch feeding of adapted cells in a microcarrier culture with a cocktail of glucose and amino acids resulted in increases in cell yields of 80% compared to unfed controls.

Adaptation, Physiological↗
PubMed1990

A systems model of chronic musculo-skeletal pain.

A comprehensive systems model of chronic musculo-skeletal pain is presented. Physical and mechanical events may impinge directly upon the organism to produce pain. In addition life experience, as interpreted by each individual, may result in unpleasant affect which may lead through three psychosomatic pathways to musculo-skeletal pain. The suggested pathways are conversion, dysponesis and neurotransmitter disturbance. It is suggested that the construing of the self as being "ill", "an invalid" or a "pain person" is a crucial step in the development of the chronic pain syndrome and that therapies which fail to change this self-construct are unlikely to meet with long-term success.

Chronic Disease↗
PubMed1990

The effect of radiation and cytotoxic platinum compounds on the growth of normal and tumour bladder explant cultures.

Using an explant tissue culture model developed by this group for use with human surgical and biopsy specimens, data are presented showing the response of normal and tumor bladder urothelium to radiation in combination with cis- and carboplatin. Cellular response is measured after two weeks in culture as a reduction in the extent of outgrowth from the explant. The outgrowth has been shown to be growing and to be epithelial. Results showed that when either drug or radiation is used singly, the tumour is resistant to treatment while the normal cells are severely affected. However, appropriate combinations of either drug with radiation reverse the unfavourable therapeutic ratio and result in higher tumour cell kill. The model may be useful for investigating mechanisms of radiation/chemotherapy action at the cellular level and, if integrated into appropriate clinical trials, may serve as an easy-to-use in vitro test for optimising single agent or combination therapy regimens.

Carboplatin↗
PubMed1989

A beltless tocodynamometer--a preliminary report.

The clinical usefulness of a newly developed beltless external tocodynamometer system was evaluated in a group of 56 patients in active, early, premature, or false labor. The uterine activity records so obtained were compared with those made in the same patients using the tocodynamometer with belt (49 patients) and the intrauterine pressure catheter (seven patients). The records were classified as "usable" if the baseline was above zero and the peak of the recorded contraction was at least 15 mmHg above the baseline. Both systems were studied under similar clinical conditions. Overall, of the 7434 minutes of recordings in 49 patients using the beltless system, 7008 minutes (94%) were usable. In contrast, only 2515 out of 5667 minutes (45%) of recordings made with the belted system were usable (P less than .001). Seven additional patients were monitored simultaneously with the beltless tocodynamometer and the intrauterine pressure catheter systems. Of the 1367 minutes' total monitoring time, the recovery rates of usable data for the beltless and intrauterine pressure catheter systems were 85 and 87%, respectively (P = not significant). These preliminary results indicate that the beltless system is a convenient, simple-to-use external tocodynamometric system that assesses uterine activity more efficiently than the belted system.

Adult↗
PubMed1988

The superiority of continuous cold blood cardioplegia in the metabolic protection of the hypertrophied human heart.

The effects of sanguineous and asanguineous cardioplegia on the generation of myocardial acid in the hypertrophied human heart during aortic clamping and reflow were elucidated by continuous intraoperative monitoring of myocardial pH in 42 patients undergoing valve replacement, with or without coronary bypass. The patients were divided into three groups: Group I (n = 14) received intermittent crystalloid cardioplegia; group II (n = 14) received intermittent blood cardioplegia; and group III (n = 14) received continuous blood cardioplegia. The groups were matched according to six previously elucidated determinants of myocardial acidosis. Measurements were made of myocardial pH, hydrogen ion concentration ([H+]), and the difference in pH units between myocardial pH and the pH of neutrality of water at the corresponding temperature (delta pHn). Throughout aortic clamping, myocardial pH in groups I and II fell significantly by 0.46 +/- 0.08 and 0.15 +/- 0.07 units, respectively (p less than 0.001) between the groups). In contrast, myocardial pH remained statistically unchanged throughout aortic clamping in group III (p less than 0.001 compared to groups I and II). Similar relationships were observed in [H+] and delta pHn during aortic clamping. During the early reflow, myocardial acidosis was observed in all three groups and delta pHn in group III increased from -0.26 +/- 0.10 at the end of aortic clamping to -0.57 +/- 0.07 during reperfusion (p less than 0.03). Patients in groups II and III required significantly less inotropic and mechanical cardiac support than patients in group I (p = 0.017). Hence, although continuous blood cardioplegia does not completely prevent acid accumulation during reflow, it provides better metabolic protection of the hypertrophied human heart than either intermittent crystalloid or intermittent blood cardioplegia.

Aged↗
PubMed1988

Light and electron microscope localization of the microtubule-associated tau protein in rat brain.

We have studied the distribution of microtubule-associated tau proteins in rat brain using monoclonal and affinity-purified polyclonal antibodies. Tau staining is prominent in axons in white matter areas of brain, as reported by Binder et al. (1985). In addition, we also find tau protein in neuron cell bodies, especially in the brain stem and basal ganglia and in the cell bodies of interfascicular oligodendroglia. Using electron microscopy, tau antibodies and colloidal gold-labeled second antibodies, gold particles are found associated with microtubules in axons and in the cytoplasm of cell bodies, while the nuclei, mitochondria, and myelin remain unlabeled. In double-staining experiments, tau staining co-localizes with that of tubulin. Our studies indicate that tau proteins are more widely distributed in brain than previously reported and cannot be used as an exclusive marker for axons.

Animals↗
PubMed1987

Ureteral meatotomy by Sachse urethrotome in the management of lower ureteral stones.

From January 1981 to June 1985 inclusive 170 patients were hospitalized for transurethral ureteral stone manipulation. A meatotomy with the Sachse urethrotome was done in 46 of these patients because the stone was impacted in the intramural ureter or the basket containing the stone became impacted. This method resulted in successful endoscopic removal of the stones in 43 patients.

Adult↗