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Biomedical subjects

J M Turner

Publications and source records attributed to J M Turner.

At least 19 recordsLinked to original sources

Behavioural predictors of subsequent hepatitis C diagnosis in a UK clinic sample of HIV positive men who have sex with men.

OBJECTIVE: To explore the associations between self reported high risk sexual behaviours and subsequent diagnosis with hepatitis C virus (HCV) infection. METHODS: The Sex, Health and Anti-Retrovirals Project (SHARP) was a cross sectional study of sexual behaviour in HIV positive, men who have sex with men (MSM) attending a London outpatient clinic. From July 1999 to August 2000 participants completed a computer assisted self interview questionnaire (CASI) on recent sexual behaviour, recreational drug use, and detailed reporting of the last two sexual episodes involving different partners. Results were combined with routine clinic data and subsequent testing for HCV up to 21 April 2005. A new HCV diagnosis was defined as anti-HCV antibody seroconversion or positive HCV RNA following a previous negative. Incident rate ratios (IRR) were calculated using Poisson regression in Stata (version 9). Men contributed time at risk from interview until either their diagnosis or their last negative test result. RESULTS: Of the 422 men who completed questionnaires, 308 (73%) had sufficient clinical and HCV testing data available for analysis. Incident HCV infection was identified in 11 men. Unprotected anal intercourse, more than 30 sex partners in the past year, higher numbers of new anal sex partners, rimming (oro-anal sex), fisting, use of sex toys, and intranasal recreational drug use were associated with HCV. In multivariate analysis only fisting remained associated with HCV (adjusted IRR 6.27, p = 0.005). CONCLUSIONS: In this study of HIV positive MSM, fisting is strongly associated with HCV infection. Where individuals report high risk sexual behaviours, clinicians should offer appropriate testing for HCV infection.

Adult↗

Endobronchial ultrasound to assess airway wall thickening: validation in vitro and in vivo.

Endobronchial ultrasound (EBUS) allows identification of airway wall structures and could potentially be utilised for in vivo studies of airway thickening in asthma. The present study investigated whether inflation of the fluid-filled balloon sheath over the transducer (necessary to provide sonic coupling with the airway wall) influenced in vitro measurements. In vivo comparability of EBUS with high resolution computed tomography scanning (HRCT), an established method for measuring wall thickness, was determined in control subjects. The airway diameter and wall thickness were studied using EBUS in 24 cartilaginous airways obtained from four sheep, before and after balloon sheath inflation during immersion in saline. To assess EBUS versus HRCT comparability of airway measures in vivo, 12 control subjects underwent imaging of the posterior basal bronchus of the right lower lobe by both techniques. Intra- and interobserver agreement were also assessed. Results with and without the balloon sheath gave comparable measures of airway internal diameter and wall thickness in vitro. Statistical analysis showed agreement between EBUS and HRCT, and intra- and interobserver variability in vivo. The current study concludes that endobronchial ultrasound, which does not present a radiation risk, could be utilised in the in vivo study of cartilaginous airway wall remodelling in respiratory diseases, such as asthma.

Adult↗

Fmoc solid phase synthesis of polyamides containing pyrrole and imidazole amino acids.

[structure: see text]. Polyamides containing N-methylimidazole (Im) and N-methylpyrrole (Py) amino acids are synthetic ligands that have an affinity and specificity for DNA comparable to those of many naturally occurring DNA binding proteins. A machine-assisted Fmoc solid phase synthesis of polyamides has been optimized to afford high stepwise coupling yields (>99%). Two monomer building blocks, Fmoc-Py acid and Fmoc-Im acid, were prepared in multigram scale. Cleavage by aminolysis followed by HPLC purification affords up to 200 mg quantities of polyamide with purities and yields greater than or equal to those reported using Boc chemistry. A broader set of reaction conditions will increase the number and complexity of minor groove binding polyamides which may be prepared and help ensure compatibility with many commercially available peptide synthesizers.

Amino Acids↗

Predictors of low bone density in young adolescent females with anorexia nervosa and other dieting disorders.

OBJECTIVE: To compare the bone density of adolescent patients with anorexia nervosa with adolescent patients with other dieting disorders and to evaluate risk factors for low bone density in these patients. METHOD: Sixty-nine consecutive female patients referred to an adolescent eating disorders clinic were studied by interview, blood sampling, body composition, and lumbar spine bone density measurement using dual energy X-ray absorptiometry. RESULTS: Although patients with anorexia nervosa were more malnourished, their bone density was similar to other dieting patients. Patients were divided into a low and normal bone density group irrespective of psychiatric diagnosis. Patients with low bone density had dieted for longer, had lower lean body mass, more often had not achieved menarche, and had longer duration of secondary amenorrhea and lower estrogen levels. DISCUSSION: Irrespective of clinical diagnosis, adolescents with dieting disorders have increased risk of low bone density when malnutrition commences early in puberty and is associated with reduced lean body mass and impaired ovarian function.

Adolescent↗

Recombinational DNA double-strand breaks in mice precede synapsis.

In Saccharomyces cerevisiae, meiotic recombination is initiated by Spo11-dependent double-strand breaks (DSBs), a process that precedes homologous synapsis. Here we use an antibody specific for a phosphorylated histone (gamma-H2AX, which marks the sites of DSBs) to investigate the timing, distribution and Spo11-dependence of meiotic DSBs in the mouse. We show that, as in yeast, recombination in the mouse is initiated by Spo11-dependent DSBs that form during leptotene. Loss of gamma-H2AX staining (which in irradiated somatic cells is temporally linked with DSB repair) is temporally and spatially correlated with synapsis, even when this synapsis is 'non-homologous'.

Animals↗

M31 and macroH2A1.2 colocalise at the pseudoautosomal region during mouse meiosis.

Progression through meiotic prophase is associated with dramatic changes in chromosome condensation. Two proteins that have been implicated in effecting these changes are the mammalian HP1-like protein M31 (HP1beta or MOD1) and the unusual core histone macroH2A1.2. Previous analyses of M31 and macroH2A1.2 localisation in mouse testis sections have indicated that both proteins are components of meiotic centromeric heterochromatin and of the sex body, the transcriptionally inactive domain of the X and Y chromosomes. This second observation has raised the possibility that these proteins co-operate in meiotic sex chromosome inactivation. In order to investigate the roles of M31 and macroH2A1.2 in meiosis in greater detail, we have examined their localisation patterns in surface-spread meiocytes from male and female mice. Using this approach, we report that, in addition to their previous described staining patterns, both proteins localise to a focus within the portion of the pseudoautosomal region (PAR) that contains the steroid sulphatase (Sts) gene. In light of the timing of its appearance and of its behaviour in sex-chromosomally variant mice, we suggest a role for this heterochromatin focus in preventing complete desynapsis of the terminally associated X and Y chromosomes prior to anaphase I.

Animals↗

An efficient benchtop system for multigram-scale kinetic resolutions using aldolase antibodies.

The preparative scale kinetic resolution of racemic aldols 1-4 using aldolase antibodies 38C2 (Aldrich no. 47995-0) and 84G3 (Aldrich no. 52785-8) is described. These reactions use a biphasic aqueous/organic solvent system that allows the catalyst to be reused. Reaction scales range from miligrams to grams, with 0.0086 to 0.12 mol% of antibody binding sites. Because antibodies 38C2 and 84G3 have opposite enantioselectivities, both aldol product enantiomers are accessible by kinetic resolution.

Aldehydes↗

Non-heart-beating organ donors: a potential source of islets for transplantation?

BACKGROUND: The shortage of organ donors relative to the number of patients on transplant waiting lists has led to a renewed interest in the use of non-heart-beating (NHB) organ donors in many centers. The lack of donors is also a problem for islet transplantation. The disparity between donor organs and potential recipients is further exacerbated by the requirement to transplant a large number of islets to increase the chance of success and the high level of variability in islet isolation yield. Non-heart-beating (NHB) donors have not previously been assessed as a source of islets for transplantation, and it is unknown what affects the additional factor of warm ischemic injury associated with NHB organs may have on the success of islet isolation. METHODS: This study assesses the yield and function of islets from NHB donors and compares the results with islets obtained from heart-beating brain-dead (HB) donors. RESULTS: There were no differences in the yield of islets per gram of pancreas, 1788 (0-4620) NHB vs. 1580 (26-2544) HB (median, range). The secretory function was also similar in both groups, with stimulation indices of 0.71-3.49 for NHB vs. 0.30-3.57 for HB (overall range). There was no correlation between islet yield and warm ischemia time in the NHB donor group. CONCLUSIONS: In conclusion, the study has demonstrated that it is possible to isolate large numbers of islets from NHB donor pancreata and that, where NHB donor programs exist, these could provide a significant addition to the number of potentially transplantable islets.

Adult↗

Structural effects of DNA sequence on T.A recognition by hydroxypyrrole/pyrrole pairs in the minor groove.

Synthetic polyamides composed of three types of aromatic amino acids, N-methylimidazole (Im), N-methylpyrrole (Py) and N-methyl-3-hydroxypyrrole (Hp) bind specific DNA sequences as antiparallel dimers in the minor groove. The side-by-side pairings of aromatic rings in the dimer afford a general recognition code that allows all four base-pairs to be distinguished. To examine the structural consequences of changing the DNA sequence context on T.A recognition by Hp/Py pairs in the minor groove, crystal structures of polyamide dimers (ImPyHpPy)(2) and the pyrrole counterpart (ImPyPyPy)(2) bound to the six base-pair target site 5'-AGATCT-3' in a ten base-pair oligonucleotide have been determined to a resolution of 2.27 and 2.15 A, respectively. The structures demonstrate that the principles of Hp/Py recognition of T.A are consistent between different sequence contexts. However, a general structural explanation for the non-additive reduction in binding affinity due to introduction of the hydroxyl group is less clear. Comparison with other polyamide-DNA cocrystal structures reveals structural themes and differences that may relate to sequence preference.

Adenine↗

Analysis of male meiotic "sex body" proteins during XY female meiosis provides new insights into their functions.

During male meiosis in mammals the X and Y chromosomes become condensed to form the sex body (XY body), which is the morphological manifestation of the process of meiotic sex chromosome inactivation (MSCI). An increasing number of sex body located proteins are being identified, but their functions in relation to MSCI are unclear. Here we demonstrate that assaying male sex body located proteins during XY female mouse meiosis, where MSCI does not take place, is one way in which to begin to discriminate between potential functions. We show that a newly identified protein, "Asynaptin" (ASY), detected in male meiosis exclusively in association with the X and Y chromatin of the sex body, is also expressed in pachytene oocytes of XY females where it coats the chromatin of the asynapsed X in the absence of MSCI. Furthermore, in pachytene oocytes of females carrying a reciprocal autosomal translocation, ASY associates with asynapsed autosomal chromatin. Thus the location of ASY to the sex body during male meiosis is likely to be a response to the asynapsis of the non-homologous regions [outside the pseudoautosomal region (PAR)] of the heteromorphic X-Y bivalent, rather than being related to MSCI. In contrast to ASY, the previously described sex body protein XY77 proved to be male sex body specific. Potential functions for MSCI and the sex body are discussed together with the possible roles of these two proteins.

Animals↗

Design and fabrication of a half-beam wedge for treatment of breast patients.

PURPOSE: The Radiation Oncology Department of Kansas University Cancer Center on the average treats approximately 60 breast patients per year. Many of them require large field sizes with widths greater than 20 cm. Our purpose is to design a half-beam wedge that is lighter in weight than a standard wedge for larger field sizes. This could replace the compensator and reduce the number of monitor units. We have designed and fabricated half-beam wedges for a Varian linear accelerator, with the angles of 15, 30 and 45 degrees for a 6 MV photon beam. A set of dosimetry data for these wedges was entered into a treatment planning computer. The treatment plans generated using these newly designed wedges were compared with those using standard wedges. METHODS AND MATERIALS: From basic principles, the geometry for the design of the wedges was calculated for three angles, 15, 30 and 45. Using trays provided by Varian, three brass wedges were milled and attached to the trays. Measurements were taken in a water phantom with three wedge angles, 15, 30 and 45, for treatment planning purposes. CONCLUSION: The design and fabrication of a half-beam wedge for the use of treatment with large field sizes could reduce the need for fabrication of a compensator. This would also reduce the time required for treatment and give a better dose distribution.

Breast Neoplasms↗

Why are familiar-only experiences more frequent for voices than for faces?

Hanley, Smith, and Hadfield (1998) showed that when participants were asked to recognize famous people from hearing their voice, there was a relatively large number of trials in which the celebrity's voice was felt to be familiar but biographical information about the person could not be retrieved. When a face was found familiar, however, the celebrity's occupation was significantly more likely to be recalled. This finding is consistent with the view that it is much more difficult to associate biographical information with voices than with faces. Nevertheless, recognition level was much lower for voices than for faces in Hanley et al.'s study, and participants made significantly more false alarms in the voice condition. In the present study, recognition performance in the face condition was brought down to the same level as recognition in the voice condition by presenting the faces out of focus. Under these circumstances, it proved just as difficult to recall the occupations of faces found familiar as it was to recall the occupations of voices found familiar. In other words, there was an equally large number of familiar-only responses when faces were presented out of focus as in the voice condition. It is argued that these results provide no support for the view that it is relatively difficult to associate biographical information with a person's voice. It is suggested instead that associative connections between processing units at different levels in the voice-processing system are much weaker than is the case with the corresponding units in the face-processing system. This will reduce the recall of occupations from voices even when the voice has been found familiar. A simulation was performed using the latest version of the IAC model of person recognition (Burton, Bruce, & Hancock, 1999) which demonstrated that the model can readily accommodate the pattern of results obtained in this study.

Adolescent↗

Chemical approaches to control gene expression.

A current goal in molecular medicine is the development of new strategies to interfere with gene expression in living cells in the hope that novel therapies for human disease will result from these efforts. This review focuses on small-molecule or chemical approaches to manipulate gene expression by modulating either transcription of messenger RNA-coding genes or protein translation. The molecules under study include natural products, designed ligands, and compounds identified through functional screens of combinatorial libraries. The cellular targets for these molecules include DNA, messenger RNA, and the protein components of the transcription, RNA processing, and translational machinery. Studies with model systems have shown promise in the inhibition of both cellular and viral gene transcription and mRNA utilization. Moreover, strategies for both repression and activation of gene transcription have been described. These studies offer promise for treatment of diseases of pathogenic (viral, bacterial, etc.) and cellular origin (cancer, genetic diseases, etc.).

Animals↗

Influences of age, performance, and item relatedness on verbatim and gist recall of verb-noun pairs.

Age differences in adults' memory for performed actions (e.g., wave hand) are sometimes smaller than age differences in memory for nonperformed phrases. In this study, we examined the conditions under which performance reduces age differences in recall. Younger and older adults performed or read verb-noun phrases that were either related (e.g., actions performed in a kitchen) or unrelated. Performance did not reduce age differences in recall of the exact verbs and nouns used to describe an action, but performance did reduce age differences in memory for the gist of related actions. Older adults especially had difficulty recalling the exact verb used to describe the action. These results suggest that older adults may have better memory for actions than is revealed by tests of verbatim recall. They may remember performing the action but not remember the exact words used to describe the action.

Adolescent↗

A structural basis for recognition of A.T and T.A base pairs in the minor groove of B-DNA.

Polyamide dimers containing three types of aromatic rings-pyrrole, imidazole, and hydroxypyrrole-afford a small-molecule recognition code that discriminates among all four Watson-Crick base pairs in the minor groove. The crystal structure of a specific polyamide dimer-DNA complex establishes the structural basis for distinguishing T.A from A.T base pairs. Specificity for the T.A base pair is achieved by means of distinct hydrogen bonds between pairs of substituted pyrroles on the ligand and the O2 of thymine and N3 of adenine. In addition, shape-selective recognition of an asymmetric cleft between the thymine-O2 and the adenine-C2 was observed. Although hitherto similarities among the base pairs in the minor groove have been emphasized, the structure illustrates differences that allow specific minor groove recognition.

Adenine↗

Recognition of the four Watson-Crick base pairs in the DNA minor groove by synthetic ligands.

The design of synthetic ligands that read the information stored in the DNA double helix has been a long-standing goal at the interface of chemistry and biology. Cell-permeable small molecules that target predetermined DNA sequences offer a potential approach for the regulation of gene expression. Oligodeoxynucleotides that recognize the major groove of double-helical DNA via triple-helix formation bind to a broad range of sequences with high affinity and specificity. Although oligonucleotides and their analogues have been shown to interfere with gene expression, the triple-helix approach is limited to recognition of purines and suffers from poor cellular uptake. The subsequent development of pairing rules for minor-groove binding polyamides containing pyrrole (Py) and imidazole (Im) amino acids offers a second code to control sequence specificity. An Im/Py pair distinguishes G x C from C x G and both of these from A x T/T x A base pairs. A Py/Py pair specifies A,T from G,C but does not distinguish AT from T x A. To break this degeneracy, we have added a new aromatic amino acid, 3-hydroxypyrrole (Hp), to the repertoire to test for pairings that discriminate A x T from T x A. We find that replacement of a single hydrogen atom with a hydroxy group in a Hp/Py pairing regulates affinity and specificity by an order of magnitude. By incorporation of this third amino acid, hydroxypyrrole-imidazole-pyrrole polyamides form four ring-pairings (Im/Py, Py/Im, Hp/Py and Py/Hp) which distinguish all four Watson-Crick base pairs in the minor groove of DNA.

Amino Acids↗

The contingent negative variation in an odor labeling paradigm.

Fifteen subjects participated in an experiment designed to assess the contingent negative variation (CNV) during the labeling of odors and shapes. Odors or shapes were presented (S1) and followed 3 s later by a lexical label (A, B, or C) (S2). In 75% of the trials, the S2 was the correct label for the odor or shape. In the remaining trials, the S2 was an incorrect label. Subjects' olfactory performance was correlated with both the CNV during in the S1/S2 interval and also the P300 following the S2 stimulus. The CNV over the left frontal area was significantly larger in the olfactory phase of the experiment. CNV activity also correlated with olfactory performance such that subjects with the largest odor-related CNVs had the best olfactory performance. Although P300 differed as a function of label matches versus mismatches, no odor-specific effects or correlations were found.

Adolescent↗