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Biomedical subjects

D Pearson

Publications and source records attributed to D Pearson.

At least 145 records · Page 8Linked to original sources

The stability of 99Tcm-DTPA in an aerosol delivery system.

99Tcm-DTPA is now widely used in aerosol nebulizers for routine ventilation lung scanning. The stability of a commercially available DTPA kit has been measured when used in an aerosol delivery system and compared with the stability when stored in the parent vial according to the manufacturer's instructions. No significant breakdown was measured up to 8 h after reconstitution in the parent vial and up to 3 h when used as an aerosol. Values of the half time of clearance of DTPA aerosols in a group of 23 patients are compared with values given in the literature.

Adolescent↗

Exon-intron boundary sliding in the generation of two mRNAs coding for porcine urokinase-like plasminogen activator.

We have analyzed four full-length cDNA clones to porcine urokinase-like plasminogen activator (uPA) mRNA. DNA sequencing revealed a deletion of 27 nucleotides in one cDNA. The comparison of cDNA and genomic sequences indicated that this length polymorphism was due to an alternative splicing of two potential 5' splice sites to a unique 3' splice site. As the difference was 27 nucleotides (corresponding to 9 amino acids) and there was no termination codon within the same reading frame in this region, the two different mRNAs might be equally biologically active.

Animals↗

Mutations preventing expression of sup3 tRNASer nonsense suppressors of Schizosaccharomyces pombe.

Suppression of nonsense codons in Schizosaccharomyces pombe by sup3-e tRNASerUGA or sup3-i tRNASerUAA is reduced or abolished by mutations within the suppressor locus. Twenty-five suppressor-inactive sup3-e genes and thirteen mutant sup3-i genes were isolated from S. pombe genomic clone banks by colony hybridization. Sequence analysis of these revertant alleles corroborates genetic evidence for mutational hotspots within the sup3 tRNA gene. Fifteen types of point mutations or insertions were found. Many of these replace bases which are highly or completely conserved in eucaryotic tRNA genes. Transcription of the altered sup3 genes in a Saccharomyces cerevisiae extract enabled the identification of mutations which affect the rate of 5'-end maturation or splicing of the tRNA precursors or both. A total of seven mutations were found which alter transcriptional efficiencies. Of these, five are located outside the internal transcription control regions.

Ascomycota↗

cDNA and gene nucleotide sequence of porcine plasminogen activator.

We have isolated cDNA and genomic clones coding for porcine plasminogen activator (urokinase, uPA). The cDNA is 2375 nucleotides long: it consists of a 5'-non-coding region (104 nucleotides), an open reading frame of 1329 nucleotides, and 3'-non-coding region of 942 nucleotides apart from the poly A tail. The genomic segment corresponding to the transcribed sequence is 5.85 kb long; it is composed of 11 exons and 10 introns. The 5'-flanking genomic region contains a number of sequences of potential regulatory significance, including possible hormone receptor binding sites and a sequence which we tentatively propose may be involved in activation of transcription by cAMP. The full sequence of both cDNA and genomic clones, the latter including 1.3 kb of flanking region, is presented and discussed, and the deduced amino acid sequence compared with that of human uPA.

Amino Acid Sequence↗

Effects of adrenaline and alpha adrenergic antagonists on platelet aggregation in whole blood: evaluation of electrical impedance aggregometry.

The effects of adrenaline and alpha adrenergic antagonists on platelet aggregation in whole blood were assessed by electrical impedance. These effects were then compared to those found in platelet rich plasma assessed by both optical and impedance methods. Our data demonstrate a number of difficulties in attempting to measure platelet responsiveness by electrical impedance and re-emphasise the need for caution in interpretation of in vitro platelet aggregation studies in terms of their clinical relevance.

Adrenergic alpha-Antagonists↗

Human platelet alpha 2-adrenoceptors: relationship between radioligand binding studies and adrenaline-induced aggregation in normal individuals.

Using the alpha 2-adrenoceptor selective radioligand [3H]yohimbine maximum binding capacities (Bmax), dissociation constants (KD), and the affinity (KI) of adrenaline for the binding sites were measured in platelets obtained from a group of 42 normal individuals. These results were compared with the efficacy of adrenaline induced aggregation in platelet rich plasma in the same subjects. Wide interindividual variation was found in Bmax values as measured in whole platelets (sites/platelet) or platelet lysates (fmol/mg protein) and in KI values for adrenaline displacement of [3H]yohimbine binding. Adrenaline's ability to induce platelet aggregation measured as the concentration required to achieve half maximal aggregation assessed from dose-response curves showed similar interindividual variation. No correlation was found, however, between alpha 2-adrenoceptor status as assessed by radioligand binding studies and the functional studies. These results suggest that the present understanding of the relationship between alpha 2-adrenoceptor occupation and platelet aggregation may be incorrect.

Adult↗

Functional significance of the platelet alpha2-adrenoceptor: studies in patients with myeloproliferative disorders.

Platelet alpha-adrenoceptor status was examined in 35 patients with myeloproliferative disorders (MPD) and 35 normal controls by means of radioligand binding studies with 3H-yohimbine (3H-YOH) and in vitro platelet function tests. A group of 'adrenaline insensitive' MPD patients identified in the functional studies were found to be identical to normal controls and other MPD patients with respect to their alpha 2-adrenoceptor status as assessed by the binding studies. Possible explanations for the dissociation between radioligand binding studies and functional responses in the platelet are discussed.

Adenine Nucleotides↗

The Schizosaccharomyces pombe sup3-i suppressor recognizes ochre, but not amber codons in vitro and in vivo.

The inefficient suppressor sup3-i of the fission yeast Schizosaccharomyces pombe is an ochre suppressor. Sup3-i was derived from the efficient serine inserting UGA suppressor sup3-e. The cloning and sequencing of the sup3-i gene indicate that the suppressor is different from the parent sup3-e by a C----T substitution in the sequence coding for the middle position of the anticodon. In vitro translation assays supplemented with purified sup3-i tRNA and programmed with Xenopus globin mRNAs lead to the accumulation of a readthrough product in response to UAA termination signals, but not in response to UGA termination codons. Transformation of Saccharomyces cerevisiae nonsense mutant strains with plasmid DNA carrying the S. pombe sup3-i gene, led to ochre, but not amber or UGA suppression in vivo.

Alleles↗

Mutations affecting excision of the intron from a eukaryotic dimeric tRNA precursor.

The nucleotide sequences of a Schizosaccharomyces pombe opal suppressor serine tRNA gene (sup9-e) and of 12 in vivo-generated mutant genes, which have lost the ability to suppress UGA mutations, have been determined. Analysis of the expression of these genes in Saccharomyces cerevisiae in vitro and in vivo systems has revealed defects in tRNA gene transcription and precursor tRNA processing. Single base changes in the D-loop, the intron and the extra arm affect the efficiency of splicing of the tRNA precursors while an anti-codon stem mutation may affect the accuracy of this process. Two mutations which occur in the intervening sequence of the sup9-e gene allow an alternate tRNA base pairing configuration. Transcription of the sup9-e gene and of the adjacent tRNAMet gene (located 7 bp downstream) is essentially abolished in vivo by a G----A19 mutation in the tRNASer gene, suggesting that tRNAMet may be derived solely via processing of the tRNASer-tRNAMet dimeric precursor.

Ascomycota↗

Promoting effect of 4-dimethylaminoazobenzene on enzyme altered foci induced in rat liver by N-nitrosodiethanolamine.

Female Wistar rats were treated sequentially with 4-dimethylaminoazobenzene (4-DAB) and N-nitrosodiethanolamine ( NDEOL ) for periods of 6 weeks. One group received first 4-DAB (0.06% in the diet) and NDEOL (2000 p.p.m. in the drinking water) thereafter, while the second group was treated in the reversed sequence; control groups received the single agent alone. The extent of foci negative for adenosine-triphosphatase (ATPase) or positive for gamma-glutamyl-transpeptidase (gamma-GT)-activity was quantitated in liver as a means to assess carcinogenic efficacy. A very low response was obtained in rats treated first with 4-DAB and then with NDEOL whereas a strong increase in number and especially in size of foci was observed when 4-DAB was given after NDEOL . The response in this latter group was clearly over-additive. Treatment of rats with either carcinogen alone resulted in similar pattern of increases in the volumetric fraction of liver occupied by ATPase-deficient foci. A differential behaviour, however, was observed with respect to islet size. NDEOL produced large numbers of small foci whereas with 4-DAB only few foci were obtained which grew rapidly in the presence of the carcinogen. These findings are consistent with the hypothesis that 4-DAB, besides acting as an initiator, has very strong promoting activity as was to be expected from the characteristic relationship between carcinogen dose and time of liver tumour induction.

Adenosine Triphosphatases↗

Estimating total body calcium from peripheral bone measurements.

In a heterogeneous group of 12 male and 30 female patients, total body calcium (TBCa) was measured by neutron activation analysis, and bone mineral content of the distal femur and six regions of the distal radius and ulna were measured by photon absorptiometry. TBCa was an average of 71 g (9%) lower than normal in the females and 119 g (11%) lower than normal in the males. Of the forearm measurements, those of the radial shaft provided the best estimate of TBCa with a standard error of estimation (SEE) of 88 g (14% of the mean value) for female patients alone, and 113 g (16%) for the whole group. The measurement on the femur provided a better estimate with SEE 80 g (13%) for female patients and 90 g (13%) for the whole group. These SEE are comparable with the variability in TBCa between normal subjects, which has a coefficient of variation of the order of 20% in both sexes. A slightly better estimate of TBCa can be obtained by using a multiple regression equation involving both the femur and radial shaft measurements with a SEE of 74 g (12%) for female patients and 81 g (11%) for the whole group. The correlation between the estimated deficit of TBCa and the estimated deficit of bone mineral from the forearm and the femur has been calculated.

Adolescent↗

Multi-element analysis of the human body using neutron activation.

The calibration described is of the Leeds in vivo neutron activation facility for the simultaneous measurement of total body Na, Cl, P, Ca, N and K. The effects of body size and shape have been incorporated into the calibration using a variable anthropomorphic phantom. The main interfering reactions are considered, and the method by which the results are corrected for these interferences described. The accuracy and precision of the technique have been determined. The procedure is suitable for measuring the critically ill since both irradiation and counting are performed with the patient lying supine. For a whole body dose equivalent of 0.5 mSv nitrogen was measured with a coefficient of variation (CV) of 2.2%; potassium was measured in the same counting period with a CV of 1.6%. Using a dose equivalent of 5 mSv sodium (2.2%), chlorine (1.6%) and phosphorus (2.9%) were also determined; for a 10 mSv dose equivalent calcium was measured with a CV of 3%.

Body Composition↗

Memory symptoms and memory performance of neurological patients.

The spontaneous memory symptoms of 100 brain-damaged patients suffering from a variety of conditions were elicited. The most frequent types of symptom related to memory for people's names, memory for recent events occurring a few days or weeks ago, memory for a spoken message and remembering to do something. The spontaneous symptoms from 50 non-brain-damaged patients were also elicited. There was a considerable degree of overlap between the type and incidence of symptoms in brain-damaged and control patients. Some symptoms (e.g. remembering people's names) were reported by a similar proportion of control as brain-damaged patients. A few symptoms (e.g. spatial disorientation, temporal disorientation) were reported by brain-damaged patients but not by any control patients. One symptom (remembering to do something) occurred more frequently in the control group of patients than in the brain-damaged group. The relationship between memory symptoms and memory performance was examined in a group of head-injured patients. A short questionnaire on memory symptoms was completed by each patient and by a close observer, and the head-injured subjects also performed tests of immediate and delayed recall. Although there was a highly significant correlation between degree of memory impairment as perceived by the patient and as perceived by an observer, there was generally a low correlation between subjective or observed memory impairment and scores on commonly used clinical memory tests.

Adolescent↗

Human chorionic gonadotrophin secreting pineal germinoma and precocious puberty.

A 10 1/2 year old boy presented with raised intracranial pressure and precocious puberty caused by a human chorionic gonadotrophin (HCG) secreting pineal germinoma. After craniospinal irradiation he improved clinically and his HCG concentration fell to an undetectable value. Two years later he remains well. Pineal germinomas are highly radiosensitive obviating the need for difficult surgery associated with high mortality.

Brain Neoplasms↗

Altered behavioral response to a D2 agonist, LY141865, in spontaneously hypertensive rats exhibiting biochemical and endocrine responses similar to those in normotensive rats.

LY141865, a dopamine agonist selective for D2 dopamine receptors, caused hypomotility at low doses (0.01 and 0.1 mg/kg) and hypermotility at high doses (1 and 10 mg/kg) after i.p. injection into normotensive rats (WKY). In age-matched hypertensive rats (SHR), LY141865 caused hypomotility (not hypermotility) at all of these doses. The basal locomotor activity was higher in SHR than in WKY, but striatal concentrations of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, and of serotonin and its metabolite, 5-hydroxyindoleacetic acid, were not different between the two groups of rats. The specific binding of a dopamine receptor radioligand, tritiated pergolide, in striatum and mesolimbic regions, did not differ in SHR compared with WKY. In contrast to the lack of locomotor stimulation in SHR, other dopaminergic responses to LY141865 occurred in SHR as well as WKY. For instance, LY141865 decreased striatal and mesolimbic concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid, increased striatal and mesolimbic concentrations of acetylcholine, decreased hypothalamic concentrations of epinephrine, increased serum corticosterone concentration and decreased serum prolactin concentration in SHR as in WKY. Because radioligand-labeled dopamine receptors and several LY141865 responses mediated by dopamine receptors did not differ appreciably in SHR compared with WKY, the lack of behavioral hypermotility in response to LY141865 in SHR may be due to abnormalities in some synaptic mechanisms beyond dopamine receptor activation that are involved in the expression of increased locomotion in response to the dopamine agonist.

Animals↗