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Biomedical subjects

A Taylor

Publications and source records attributed to A Taylor.

At least 433 records · Page 24Linked to original sources
PubMed1994

Findings of an external quality assessment scheme for determining aluminum in dialysis fluids and water.

The analytical performance of laboratories participating in the dialysis fluids and water aluminum program of the Guildford External Quality Assessment Scheme over the period 1986-1993 has been reviewed. For aluminum concentrations > 3.33 mumol/L in dialysis fluids, the between-laboratory CV has fallen from approximately 36% to 23%, whereas for specimens of water the reduction was from 36% to approximately 18%. Improvements at lower concentrations were less impressive. Performance of individual participants varied; only a few consistently provided accurate results. Many of the participants are able to measure serum aluminum well, so lack of expertise is not responsible for poor results. We suggest that matrix effects associated with different specimen types have a significant influence on performance and that due account is not always taken of these factors. Resolution of these problems would be aided by appropriate reference materials.

Aluminum↗
PubMed1994

Reproducibility of thallium-201 exercise SPECT studies.

UNLABELLED: A detailed analysis of intrapatient reproducibility of exercise SPECT thallium studies is presented. METHODS: Twenty patients in stable condition were re-examined with exercise-redistribution SPECT201 Tl within 3-9 days without intervening procedures. At peak stress, 3.5 mCi 201Tl were given intravenously 1 min prior to exercise termination. SPECT imaging started at 5 and 180 min. Acquisition and processing protocols were the same for all studies. Coronary angiography was performed on 19 patients and showed coronary artery disease (CAD) in 18, and no CAD in one; one patient did not have coronary arteriography. RESULTS: For 16 of 20 patients, exercise levels and ECG were comparable for both studies. Ten patients reproduced ST-segment depression; two reproduced angina; one had left bundle branch block (LBBB) on both studies after 1 min of exercise. The remaining seven patients had no ECG changes or symptoms during exercise. Four of 20 (20%) thallium scans differed: three in degree of redistribution and one (5%) in presence of a second stress defect. In three of four patients whose thallium studies showed some nonreproducibility, there were differences in exercise. Thallium results were identical in 15 of 16 patients whose ECG/exercise tests were reproducible (94%). Interobserver agreement was 95%. CONCLUSION: There was excellent reproducibility of 201Tl SPECT scintigraphy in patients who reproduced exercise test performance and symptoms.

Coronary Angiography↗
PubMed1993

Isolation of bovine kidney leucine aminopeptidase cDNA: comparison with the lens enzyme and tissue-specific expression of two mRNAs.

Aminopeptidases catalyze the hydrolysis of amino acid residues from the amino terminus of peptide substrates. Leucine aminopeptidase (LAP) from bovine lens is the best characterized aminopeptidase and the only LAP for which the amino acid sequence was determined by protein sequencing. Using this sequence information, we isolated a bovine kidney LAP cDNA and compared its deduced amino acid sequence to the published amino acid sequence for bovine lens LAP. Overall, the sequences are highly conserved. However, several differences are observed. The kidney LAP cDNA indicates a 26 amino acid extension at the amino terminus which is not found in the mature purified lens LAP. The cDNA also indicates an additional octapeptide in the C-terminal region which was not indicated in the published lens LAP amino acid sequence but which was required for best fit of crystallographic data regarding bovine lens LAP. Several other single amino acid changes were also noted. Levels of LAP transcripts were examined in bovine lens and kidney tissue as well as in cultured lens cells. Lens epithelial tissue showed only one LAP transcript (2.4 kb) whereas two transcripts (2.0 and 2.4 kb) were observed in cultured lens cells derived from epithelial tissue and in kidney tissue. Using Northern blot analysis, we correlated LAP mRNA levels with previously determined changes of LAP activity in aging lens tissue and in progressively passaged lens epithelial cells which were used to simulate aging in vitro. No differences were found in LAP mRNA levels in epithelial tissue from old and young lenses.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Estimating the population prevalence of injection drug use and infection with human immunodeficiency virus among injection drug users in Glasgow, Scotland.

Although data on the prevalence of injection drug use are an essential prerequisite for estimating the number of individuals infected with the human immunodeficiency virus (HIV), there have been few attempts to utilize statistical methods of population estimation based on multiple data sources. Data on 3,670 cases (2,866 individuals) were obtained from the HIV test register, drug treatment agencies, police records, and needle and syringe exchanges in Glasgow, Scotland, in 1990. Log-linear analysis was used to model the number of individuals in each of the sources. The model incorporating dependency among the three health care agencies (HIV test, drug treatment, and needle exchange) and independence of the police sample fitted the data well, with a residual chi 2 value of 2.9 (6 df). The expected value of the missing cell corresponding to absence from all four samples was 5,628, yielding an overall estimate of 8,494 injectors (95% confidence interval (CI) 7,491-9,721), for a prevalence rate of 1.35% for people aged 15-55 years in Glasgow during 1990. The high ratio of known to unknown injectors (1:2) resulted from the extensive coverage of known injectors and the relatively high level of overlap between the combined health care agency sample and the police sample. While further analysis demonstrated that the probability of appearing in the four samples varied by age and sex, heterogeneity in the population did not affect the choice of model or substantially alter the estimates for the total number of unknown injectors. A concurrent study of a community-wide sample of 503 injectors resulted in an HIV prevalence rate of 1.1% (95% CI 0.4-2.5%). The results of these studies were combined to produce a further estimate of 93 HIV-infected current injectors in Glasgow (95% CI 33-214).

Adolescent↗
PubMed1993

Expression of the Rz gene and the overlapping Rz1 reading frame present at the right end of the bacteriophage lambda genome.

The Rz lysis gene of bacteriophage lambda was cloned into the expression vectors, pT7-3 and pT7-7. The recombinant plasmids expressed either a protein of an unexpected 6.5-kDa size (pT7-3H and pSB54) or two proteins of 6.5 and 17.2 kDa (pBH21). The 6.5-kDa protein alone did not complement the lysis defect of the lambda Rz mutant; hence, this protein was not the Rz gene product. Complementation observed as a result of pBH21 expression thus can be ascribed to the 17.2-kDa protein, which agrees with the size based on the nucleotide sequence of Rz. The 6.5 kDa is a product of an open reading frame entirely encompassed within the Rz sequence and denoted by us Rz1. Both proteins were detectable only by autoradiography, which may mean that the genes are expressed at low rates. Polyclonal anti-Rz antibodies (Ab) were obtained by rabbit immunization with a synthetic polypeptide corresponding to an antigenic determinant of Rz defined by a computer program. The Ab reacted with the 17.2-kDa protein resulting from pBH21 expression, as well as with the 17.2-kDa protein present in the induced Escherichia coli W3350(lambda cI857Sam7) lysate.

Amino Acid Sequence↗
PubMed1993

Aminopeptidases: structure and function.

Aminopeptidases catalyze the cleavage of amino acids from the amino terminus of protein or peptide substrates. They are widely distributed throughout the animal and plant kingdoms and are found in many subcellular organelles, in cytoplasm, and as membrane components. Several aminopeptidases perform essential cellular functions. Many, but not all, of these peptidases are zinc metalloenzymes and are inhibited by the transition-state analog bestatin. Some are monomeric, and others are assemblies of relatively high mass (50 kDa) subunits. cDNA sequences are available for several aminopeptidases, and a 3-dimensional structure is available for the bovine lens enzyme. Crystallographic, electron micrographic, NMR, and photoaffinity labeling studies indicate that lens leucine aminopeptidase protomers are bilobal and that bestatin and substrates are bound in an active site, which is found in the larger lobe on each protomer. Zn2+ is involved in substrate liganding in most aminopeptidases. There is no evidence of an acyl-enzyme intermediate in hydrolysis. Amino acid sequences determined directly or deduced from cDNAs indicate some amino acid sequence homologies in organisms as diverse as Escherichia coli and mammals, particularly in catalytically important residues or in residues involved in metal ion binding.

Amino Acid Sequence↗
PubMed1993

Inhibition of bovine lens leucine aminopeptidase by bestatin: number of binding sites and slow binding of this inhibitor.

Aminopeptidases catalyze the hydrolysis of amino acid residues from the amino terminus of peptide substrates. Their activity has been implicated in myriad fundamental biochemical and physiological processes, and alterations in aminopeptidase activity have been correlated with a variety of pathologies. Nevertheless, information about this group of proteases is less well developed. Bovine lens leucine aminopeptidase (blLAP) can be considered prototypical of many enzymes in this family of peptidases. It shows common features of (1) requiring divalent metal ions for activity, (2) having a relatively large size, and (3) having slow, relatively tight binding of bestatin, a transition-state analog of the substrate PheLeu. Bovine lens LAP is the only bestatin-inhibitable aminopeptidase for which structural and mechanistic data are available. However, full exploitation of these data required knowledge of the number of inhibitor molecules bound per subunit. Independent direct binding experiments and kinetic determinations indicate that one bestatin is bound per subunit in blLAP. Ki and Ki* for formation of the initial and final complexes are approximately 1.1 x 10(-7) and 1.3 x 10(-9) M, respectively. The mode of binding is slow and competitive. The t1/2 for formation and deformation of the final enzyme-inhibitor complex is approximately 30 and 22 min, respectively, with 10(-8) M bestatin. To perform these measures, a new assay using physiological peptides (LeuGlyGly) as substrate was adapted. Taken together with prior NMR, photoaffinity labeling, and crystallographic data, these binding data allow us to propose a mechanism of the blLAP-catalyzed hydrolysis of peptides.

Aminopeptidases↗
PubMed1993

Bovine lens epithelial cells have a ubiquitin-dependent proteolysis system.

Lens cells must remove obsolete or damaged proteins produced during development, maturation and aging to maintain lens transparency. In reticulocytes removal of abnormal or obsolete proteins is thought to involve a ubiquitin-dependent proteolytic pathway. Two hallmarks of ubiquitin (Ub) dependent proteolysis have previously been demonstrated in lens cell or tissue supernatants: (1) the presence of ubiquitin conjugates, and (2) ATP-dependent proteolysis. Nevertheless, conclusive proof was lacking of a requirement for ubiquitination of substrate proteins for proteolysis. Here we show that in bovine lens epithelial cell (BLEC) supernatant, ATP-dependent proteolysis is also ubiquitin-dependent. Ubiquitin-activating enzyme (E1), the first enzyme in the cascade of ubiquitin ligation, was purified over 3000-fold from a rabbit reticulocyte lysate using Ubiquitin-Sepharose, and showed ATP-PPi exchange activity. Antiserum to E1 was prepared in goats and affinity-purified on Protein G-Sepharose. Western blot analysis revealed that both the goat antiserum and purified antibody (anti-E1(IgG)) recognize specifically E1. Anti-E1(IgG) inhibits 86% of the ATP-dependent degradation of labeled histone H2A in reticulocyte lysate and 75% of the ATP-dependent degradation in BLEC. Upon reconstitution with purified E1, 100% and 80% of proteolysis was restored in reticulocytes and BLEC supernatant, respectively. This confirms that there is a ubiquitin-dependent proteolytic system in lens.

Animals↗
PubMed1993

Molecular-clinical correlations in children and adults with fragile X syndrome.

INTRODUCTION: Fragile X syndrome is the most commonly known inherited form of mental retardation. The intellectual abilities range from a normal IQ with learning disabilities to severe mental retardation. In males, there is a tendency for IQ decline in childhood. The purpose of this study was to correlate variations of the molecular cytosine guanine guanine (CGG) amplification in the fragile X mental retardation-1 (FMR-1) gene with the clinical findings, including IQ and physical features. METHODS: Full-scale IQ and cytogenetic results in 116 individuals with the FMR-1 mutation were studied. The IQ testing was performed with age-appropriate standardized tests. Physical features were summarized in a physical index score for each patient. The FMR-1 results were determined with the OX1.9 probe and the following system was used: P1 indicates premutation; P2, large premutation to small full mutation; P3, full mutation; and P4, mosaic. RESULTS/CONCLUSIONS: The findings showed that those females with a small insert in the P1 range had a significantly higher IQ than other heterozygotes (P2, P3, and P4 categories). P4 males had a significantly higher IQ than P2 or P3 males. In cross-sectional age comparisons, the slope of the IQ decline was greater in P2 males than in P4 or P3 males.

Adolescent↗
PubMed1993

Flanking markers define the X-linked hypophosphatemic rickets gene locus.

X-linked hypophosphatemic rickets (HYP) is an X-linked dominant disorder characterized by decreased renal tubular phosphate reabsorption and consequent hypophosphatemia. The defect in tubular phosphate reabsorption is probably secondary to an unidentified humoral factor. Identification of the humoral factor and a full understanding of the pathophysiology of the disease await the identification of the HYP gene. Previously we demonstrated that DXS257 and DXS41 are flanking markers for the HYP gene. Two markers, DXS365 and DXS274, are tightly linked to the HYP gene, but investigators have been unable to determine whether they are centromeric or telomeric to the disease gene. Since tightly linked flanking markers are necessary prerequisites to obtain the gene by positional cloning techniques, we sought to determine the relative positions of these markers to the HYP gene by expanding our data base for linkage studies. We also investigated a new polymorphic probe for linkage to HYP to construct a more detailed genetic map around the HYP locus. Our data indicate that the markers DXS365, DXS274, and DXS92 are tightly linked to the HYP locus and suggest a locus order of Xtel-(DXS444/DXS315)-DXS43-(DXS257/DXS3 65)-HYP-(DXS274/DXS41/DXS92)-DXS-451- DXS319-Xeen. These results will facilitate attempts further to localize and clone the HYP gene.

Chromosome Mapping↗
PubMed1993

Fusimotor effects of midbrain stimulation on jaw muscle spindles of the anaesthetized cat.

The effects of electrical stimulation within the midbrain on fusimotor output to the jaw elevator muscles were studied in anaesthetized cats. Muscle spindle afferents recorded in the mesencephalic trigeminal nucleus were categorised as primary or secondary by their responses to succinylcholine during sinusoidal or ramp-and-hold stretches. Changes in their stretch responses during midbrain stimulation were then assessed by changes in bias and in dynamic sensitivity. Problems were encountered in interpreting changes in sine wave stretch responses of primary afferents, in some of which a very small change in firing pattern produced large changes in estimates of the response amplitude. Sine wave testing also sometimes over-estimated static effects and under-estimated dynamic effects relative to ramp responses. On other occasions a small amount of static fusimotor activity caused a marked increase in sine response amplitude, which could be wrongly interpreted as a dynamic effect. Consequently, ramp responses only were used for diagnosing fusimotor changes. The most effective region for producing pure dynamic fusimotor excitation was directly rostral to the red nucleus, extending dorsally and ventrally approximately in the course of the retroflex bundle. Stimulation of regions caudal and dorso-caudal to the red nucleus, previously designated as the mesencephalic area for dynamic fusimotor control of leg muscles, gave static or mixed static and dynamic effects on jaw spindles. The use of midbrain stimulation to identify fusimotor neurones of jaw muscles as static or dynamic would be most reliable with stimulation just rostral to the red nucleus and would require spindle afferent behaviour to be monitored at the same time with ramp stretches.

Anesthesia↗
PubMed1993

Effect of oral aluminium citrate on short-term tissue distribution of aluminium.

Aluminium (Al) concentrations in the plasma, bone, lung, liver, kidney, spleen, duodenum and brain of rats were measured 2, 4 and 24 hr after a single oral dose of 0.46 mmol as Al citrate (1:5 molar ratio). Compared with control animals, very high concentrations were found at 2 hr post-administration in plasma (539 micrograms/litre) and in all tissues except the brain where Al did not change throughout the 24-hr period. The increased levels in the liver (161 ng/g) and lung (89.7 ng/g) at 2 hr were maintained until 4 hr and then decreased. At 24 hr the plasma value decreased to 24.6 micrograms/litre as compared with the peak value of 539 micrograms/litre. In a typical soft tissue such as the kidney the peak at 2 hr of 682 ng/g decreased to 241 ng/g, which was still more than 10-fold greater than the control level. Uniquely, in the case of bone Al increased throughout the period of the experiment. Our results indicate that Al in the citrate form is readily absorbed and that it appears to equilibrate rapidly between plasma and the intracellular compartments of most soft tissues but does not readily permeate the blood-brain barrier. In a group of rats previously given silicic acid in the drinking water and co-administered with the Al dose, the tissue Al distribution pattern at 4 hr post-administration was modified in comparison with the test animals not loaded with silicic acid. Al concentrations in plasma and soft tissues were significantly reduced except for the spleen, in which Al increased, and there was complete inhibition of the very high Al uptake/deposition in bone.

Administration, Oral↗
PubMed1993

Prison experience of injecting drug users in Glasgow.

Five hundred three injecting drug users in Glasgow recruited by a multisite and citywide sampling strategy were questioned regarding their drug-taking behaviour during episodes of custody over the six months prior to interview. Fifty-two percent had been in custody during the past 6 months, 16% of these had injected while in custody. Of these 73% borrowed injecting equipment and 78% handed on used equipment to others. All those who shared, cleaned their injecting sets before use. Over half of those who injected had a source of new sets. While the potential exists for spread of HIV among drug users while in custody there is clear understanding among them of the route by which the virus is spread and also the will to prevent it.

Cross-Sectional Studies↗
PubMed1993

Case report: percutaneous retrieval of a misplaced embolization coil.

We report a case of percutaneous retrieval of a misplaced embolization coil which threatened the segmental arterial supply of a single kidney. The renal artery was steeply angulated due to a spinal scoliosis but retrieval was rapidly performed using an Amplatz gooseneck snare. This device is particularly useful when the arterial anatomy is tortuous.

Aged↗