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Biomedical subjects

G Jones

Publications and source records attributed to G Jones.

At least 145 records · Page 8Linked to original sources
PubMed2000

Associations between maternal peak bone mass and bone mass in prepubertal male and female children.

The aim of this study was to estimate heritability of bone density in premenopausal women, prepubertal male, and prepubertal female child pairs. We studied 291 pairs (mothers, mean age, 33 years, range 22-45 years; children, mean age, 7.92 years, range 7.32-8.92 years). Bone density and body composition were assessed by dual-energy X-ray absorptiometry. Height and weight were measured in both mother and child. Body size-adjusted heritability estimates for areal bone density (g/cm2) were all statistically significant (femoral neck, 59%; lumbar spine, 38%; total body, 41%) and were consistently and significantly higher in mother-daughter pairs (n = 105) as compared with mother-son pairs (n = 186). Heritability estimates for bone mineral apparent density (BMAD; g/cm3) were marginally lower but remained statistically significant at all sites (femoral neck, 51%; lumbar spine, 32%; total body, 38%). Maternal osteopenia was associated with significant reductions in bone mass at all sites in the children (femoral neck, 0.75 SD and p < 0.0001; lumbar spine, 0.61 SD and p < 0.0001; total body, 0.43 SD and p = 0.012). Mother-child bone areal bone density correlation coefficients and prediction of low bone mass in the child were greater (but this did not reach statistical significance) if the corresponding anatomical site in the mother was used for prediction with the exception of the total body. These data confirm that heritability of bone mass extends to prepubertal children and is gender- and possibly site-specific as well as under separate genetic control to growth. Furthermore, the strength of the mother-child association is such that bone density screening of mothers would make it possible to identify most prepubertal children at higher risk of osteoporosis in later life.

Absorptiometry, Photon↗
PubMed2000

Intensity and direction of competitive state anxiety as interpreted by rugby players and rifle shooters.

This study reports the findings of part of an ongoing research program examining sports performers' interpretations of competitive anxiety prior to competition. The notion of 'directional perceptions' has questioned the limited utility of examining only the intensity of competitive anxiety responses as has Jones. The purpose of this study was to examine intensity and direction, i.e., interpretation of intensity as facilitative or debilitative, of anxiety symptoms as a function of two types of sport. The types of sport were explosive (rugby league) versus fine motor skills (target rifle shooting). The sample comprised 50 male rugby league participants and 50 target rifle shooters who completed a modified version of the Competitive State Anxiety Inventory-2 prior to competition. Contingency analysis yielded a significant difference in the number of rugby players who reported somatic anxiety as facilitative and the number of rifle shooters who reported somatic states as debilitative. No such differences were evident for cognitive anxiety. Analysis of variance indicated no differences between the two groups on the intensity of cognitive and somatic anxiety, but the performers competing in rugby league interpreted both states as being more facilitative to performance; the rugby league players also had higher scores on self-confidence than the shooters. These findings provide continuing support for the measurement of directional perceptions of competitive anxiety and highlight the importance of examining individual sports.

Anxiety↗
PubMed2000

Asthma, inhaled corticosteroid use, and bone mass in prepubertal children.

The aim of this cross-sectional study was to describe the role of asthma, asthma severity, and medication usage in bone mineralization of prepubertal children. Asthma severity, medication usage, and physical activity were assessed by questionnaire and objective measures in 330 children. Bone densitometry and body composition were measured by dual-energy x-ray absorptiometry. Asthma ever was reported by 110 subjects (33%). A diagnosis of asthma was not associated with any deficit in bone mass, whereas usage of inhaled corticosteroids (ICS) in the last year (but not past use) was associated with deficits in bone in the total body (only after adjustment for confounders), particularly for doses of > or =400 microg/day. These observations support current recommendations with regard to ICS usage in children, but require confirmation in longitudinal studies.

Absorptiometry, Photon↗
PubMed2000

Molecular genetics improves the management of hereditary non-polyposis colorectal cancer.

BACKGROUND: The syndrome of hereditary non-polyposis colorectal cancer (HNPCC) can be diagnosed fairly accurately using clinical criteria and a family history. Identifying HNPCC helps to prevent large-bowel cancer, or allows cancer to be treated at an early stage. Once the syndrome has been diagnosed a family member's risk can be judged approximately from a family tree, or it can now be predicted accurately if the causative mutation is known. OBJECTIVE: This study involved attempts to improve the management of a family with HNPCC over a period of 10 years. Clinical diagnostic criteria, colonoscopic surveillance, surgical treatment, genetic counselling, molecular genetic research, and finally predictive genetic testing were applied as they evolved during this time. SUBJECTS AND METHODS: A rural general practitioner first noted inherited large-bowel cancer in the family and began screening subjects as they presented, using rigid sigmoidoscopy at the local hospital. At the time that the disorder was recognised as being HNPCC (1987), screening by means of colonoscopy at our university hospital was aimed primarily at first-degree relatives of affected individuals. After realising how many were at risk, screening was brought closer to the family. A team of clinicians and researchers visited the local hospital to identify and counsel those at risk and to perform screening colonoscopy. Family members were recruited for research to find the gene and its mutation that causes the disease, to develop an accurate predictive test and to reduce the number of subjects undergoing surveillance colonoscopies. RESULTS: There are approximately 500 individuals in this family. In the 10 years of this study the number of subjects who have been counselled for increased genetic risk or who have requested colonoscopic surveillance for HNPCC in this kindred has increased from 20 to 140. After the causative mutation was found in the hMLH1 gene on chromosome 3, a test for it has reduced the number of subjects who need screening colonoscopy by over 70%. A protocol has been devised to inform family members, to acquire material for research in order to provide genetic counselling for (pre-test and post-test) risk, and to test for the mutation. Eventually, identifying those with the mutation should focus surveillance accurately. CONCLUSIONS: The benefits of restricting screening to subjects with the mutation that causes colorectal cancer and of performing operations to prevent cancer are hard to measure accurately. However, it is likely that at least half the family members will be able to avoid colonoscopic screening, some deaths from cancer should be prevented, and the cost of preventing and treating cancer in the family should fall substantially.

Adult↗
PubMed1999

Potent and selective inhibition of varicella-zoster virus (VZV) by nucleoside analogues with an unusual bicyclic base.

We herein report the discovery of an entirely new category of potent antiviral agents based on novel deoxynucleoside analogues with unusual bicyclic base moieties. Target structures, previously known as byproducts in Pd-catalyzed coupling of terminal alkynes with 5-iodo-nucleosides, are recognized herein for the first time to be potent and selective inhibitors of varicella-zoster virus (VZV) in vitro. As an unusual structure-activity relationship we noted the absolute requirement of a long alkyl side chain, with an optimum length of C(8)-C(10), for antiviral activity. We thus report the synthesis and characterization of a series of chain-modified analogues and their extensive in vitro evaluation. The lead compounds have a ca. 300-fold enhancement in anti-VZV activity over the reference compound acyclovir, with no detectable in vitro cytotoxicity. The novel structure of these compounds, coupled with their ease of synthesis, excellent antiviral profile, and promising physical properties, makes them of great interest for possible antiviral drug development.

Antiviral Agents↗
PubMed1999

The PTEN lipid phosphatase domain is not required to inhibit invasion of glioma cells.

The tumor suppressor PTEN negatively controls the phosphoinositide 3-kinase pathway for cell survival by dephosphorylating the phospholipid substrates phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. PTEN has been proposed to dephosphorylate focal adhesion kinase and is implicated in the regulation of cell spreading and motility. We analyzed the role of PTEN in invasion using the two highly infiltrative glioma cell lines U87MG (which lacks functional PTEN) and LN229 (wild-type PTEN). After constitutive overexpression of wild-type and phosphatase-deficient (C124S) PTEN, we found significant inhibition of invasion (50-70%) independent of the PTEN status of the cell and of the catalytic core domain of PTEN. Although wild-type but not mutant (C124S) PTEN decreased PKB/Akt phosphorylation and induced a stellate morphology in U87MG cells, an accompanying reduction of focal adhesion kinase phosphorylation was not seen. We conclude that phosphatase-independent domains of PTEN markedly reduced the invasive potential of glioma cells, defining a structural role for PTEN that regulates cell motility distinct of the PKB/Akt pathway.

Brain Neoplasms↗
PubMed1999

Constitutively active MuSK is clustered in the absence of agrin and induces ectopic postsynaptic-like membranes in skeletal muscle fibers.

In skeletal muscle fibers, neural agrin can direct the accumulation of acetylcholine receptors (AChR) and transcription of AChR subunit genes from the subsynaptic nuclei. Although the receptor tyrosine kinase MuSK is required for AChR clustering, it is less clear whether MuSK regulates gene transcription. To elucidate the role of MuSK in these processes, we constructed a constitutively active MuSK receptor, MuSKneuTMuSK, taking advantage of the spontaneous homodimerization of the transmembrane domain of neuT, an oncogenic variant of the neu/erbB2 receptor. In the extrasynaptic region of innervated muscle fibers, MuSKneuTMuSK formed highly concentrated aggregates that colocalized with AChR clusters. Associated with MuSK-induced AChR clusters was a normal complement of synaptic proteins. Moreover, transcription of the AChR-epsilon subunit gene was increased, albeit via an indirect mechanism by MuSK-induced aggregation of erbB receptors and neuregulin. Although neural agrin was not required, the activity of MuSKneuTMuSK was nevertheless potentiated by ectopic expression of a muscle agrin isoform inactive in AChR clustering. To define the role of the kinase domain in the formation of a postsynaptic-like membrane, a second fusion receptor, neuneuTMuSK, which included the MuSK kinase but not the MuSK extracellular domain, was expressed. Significantly, neuneuTMuSK induced AChR clusters that colocalized with aggregates of endogenous MuSK. Taken together, it was concluded that the MuSK kinase domain is sufficient to initiate the recruitment of additional MuSK receptors, which then develop into highly concentrated aggregates by means of a positive feedback loop to induce a postsynaptic membrane in the absence of neural agrin.

Agrin↗
PubMed1999

Noctuid moths show neural and behavioural responses to sounds made by some bat-marking rings.

Coloured rings are often used for marking bats so that specific individuals can be recognized. We noticed that the rings of mouse-eared bats, Myotis myotis and Myotis blythii, in a combination of one plastic-split and one metallic ring on the same forearm, emitted sounds that were largely ultrasonic each time the rings met in flight. We recorded the ring sounds and the echolocation calls produced by the bats, and played them back to neural preparations of lesser yellow underwing moths, Noctua comes, while making extracellular recordings from the moths' A1 auditory receptors. The peak energy of the ring sounds occurred much closer in frequency to the moth's best auditory frequency (the frequency at which the moth has the lowest auditory threshold) than the peak energy of the calls, for both bat species, and the ring sounds were detected at a threshold 5-6 dB peSPL lower than the calls. Moths performed evasive manoeuvres to playbacks of ring sounds more frequently than they did to control (tape noise) sequences. These neural and behavioural responses imply that certain bats should not be marked with two rings on one wing, as this may make the bat more apparent to tympanate insects, and may therefore reduce its foraging success. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗
PubMed1999

Meningococcal disease at the University of Southampton: outbreak investigation.

In October 1997, an outbreak of meningococcal disease occurred at the University of Southampton. All six cases were first year students living in halls of residence. Microbiological characterization of case and carrier strains, case interviews, and a meningococcal carriage prevalence survey were used to investigate the outbreak. Five cases were due to serogroup C strains, one case was unconfirmed. Serotyping did not distinguish between the strains but gene sequencing permitted identification of two distinct strains in the outbreak. Although none of the cases was known to each other, three had attended the same nightclub one evening 3-4 days before illness. Meningococcal carriage rates in undergraduates were within the range expected (147/587, 25%), but no carriers of outbreak strains were identified in this sample. The findings suggest that in communities with a high degree of social interaction, the introduction of highly virulent meningococcal strains may result in enhanced transmission with clustering of cases.

Adolescent↗
PubMed1999

Vitamin D levels in prepubertal children in Southern Tasmania: prevalence and determinants.

OBJECTIVE: To describe the prevalence and determinants of 25-hydroxy D3(25(OH)D) in children. DESIGN: Cross-sectional study. SETTING: Southern Tasmania between June and November 1997. SUBJECTS: Two hundred and one 8-y old male and female children taking part in a cohort study whose principal endpoints were blood pressure and high-density lipoprotein (HDL) cholesterol. RESULTS: The mean 25(OH)D level was 79 nmol/l (s.d. 29.5, median 73, range 12-222). Boys had higher levels than girls (82.1 vs 72.8 nmol/l, P=0.02). 25(OH)D was associated with sunlight exposure in winter school holidays (r=0.20, P=0.005) and winter weekends (r=0.16, P=0.02), the month after school holidays (87.5 vs 69.5 nmol, P<0.0001) and body mass index (r=-0.23, P=0.001). Dietary intake of vitamin D was low (mean 40 IU/day, range 5.2-384) and was not associated with 25(OH)D levels (r=0.01, P=0.91). Variation in skin melanin density was weakly associated with 25(OH)D (r=0.09, P=0.19). CONCLUSIONS: Sunlight is the major determinant of vitamin D stores in our population. Neither variation in skin type within Caucasians nor diet modified this association to any significant extent. Extrapolation of these findings to sunlight bone mass associations in a very similar population suggests that a minimum level of around 50 nmol/l in the population is required for optimal bone development in prepubertal children but this needs to be confirmed with further controlled trials of vitamin D supplementation and bone mass. SPONSORSHIP: Arthritis Foundation of Australia, Roche Pharmaceuticals.

Body Mass Index↗
PubMed1999

A randomized outcome evaluation of group exercise programs in long-term care institutions.

BACKGROUND: Physical activity programs in nursing homes typically consist of seated, range of motion (ROM) exercises, regardless of resident abilities. The Functional Fitness for Long-Term Care (FFLTC) Program was designed not only to maintain ROM, but also to improve strength, balance, flexibility, mobility, and function. In addition, it was tailored to meet the needs of both high and low mobility residents. METHODS: The feasibility and efficacy of the FFLTC Program were evaluated with 68 residents (mean age 80) from five institutions. Persons were classified as low or high mobility and randomized into either the FFLTC program or a seated ROM program. Classes were conducted in groups of 4 to 10 residents by trained facility staff for 45 minutes, three times per week. Assessments at baseline and 4 months consisted of mobility, balance, gait, flexibility, functional capacity, and several upper and lower extremity strength measures. RESULTS: Attendance averaged 86% for the FFLTC and 79% for the ROM classes. Four months of exercise led to significant improvements in mobility (16%), balance (9%), flexibility (36%), knee (55%), and hip (12%) strength for the FFLTC group. Shoulder strength was the only improvement found for the ROM group. The ROM group significantly deteriorated in some areas, particularly hip strength, mobility, and functional ability. CONCLUSIONS: Institutionalized seniors, even those who are physically frail, incontinent and/or have mild dementia, can respond positively to a challenging exercise program. The FFLTC program demonstrated clear benefits over typical, seated ROM exercises. Moreover, with minimal training, the program can be safely delivered at low cost by institutional staff and volunteers.

Activities of Daily Living↗
PubMed1999

Water fluoridation, bone mass and fracture: a quantitative overview of the literature.

OBJECTIVE: To use the technique of meta-analysis to address the following research questions: Is water fluoridation associated with altered fracture risk at a population level and are the differences between studies consistent with confounding or chance variation between studies? METHOD: The data sources utilised were Medline 1966-97, reviews and bibliographies. The search terms were fluoridation, bone mass and/or fracture. We included all observational studies published in English relating water fluoridation to bone mass and/or fracture in the initial assessment. RESULTS: Water fluoridation had no evident effect on fracture risk (RR 1.02, 95% CI 0.96-1.09, n = 18 studies). There was marked heterogeneity between studies which could be explained, in part, by the combination of gender, urbanicity and study quality (R2 0.25, p = 0.05, weighted analysis). CONCLUSIONS: Water fluoridation both at levels aimed at preventing dental caries and, possibly, at higher naturally occurring levels appears to have little effect on fracture risk, either protective or deleterious, at a population level. The small effect on bone mass seen in studies performed at the individual level is consistent with this finding. Variation between studies is also likely to be due to differences in the distribution of other recognised fracture risk factors between different populations. Confirmation of these findings is required in large studies performed at the individual level.

Analysis of Variance↗
PubMed1999

The relationship of magnetic source imaging to ictal electrocorticography in a neuronavigational workspace.

Magnetic source imaging (MSI) registers magnetoencephalographic (MEG) activity to a three-dimensional MRI volume. State-of-the-art MSI allows concurrent whole head coverage, but is practically restricted to interictal recording. However, the purpose of the presurgical evaluation of epileptic patients, in which MSI is playing an increasing role, is the elucidation of the ictal epileptogenic focus. The manner in which interictal MSI activity relates to the ictal focus has not yet been adequately examined. To facilitate this analysis, we are developing techniques to precisely coregister MSI to the ictal onset zone as defined by extraoperative intracranial grid/strip monitoring. The neuronavigational workspace is a convenient area in which to precisely coregister these (and other) imaging and physiological data sets.

Cerebral Cortex↗
PubMed1999

Expression and activity of vitamin D-metabolizing cytochrome P450s (CYP1alpha and CYP24) in human nonsmall cell lung carcinomas.

Extrarenal 25-hydroxyvitamin D3-1alpha-hydroxylase is believed to play a major role in the pathogenesis of hypercalcemia associated with various types of granulomatous and lymphoproliferative diseases and certain solid tumors. In this paper, we describe the cloning of the cytochrome P450 component of the extrarenal enzyme from a human nonsmall cell lung carcinoma, SW 900. The cytochrome P450 for the extrarenal 1alpha-hydroxylase has an amino acid sequence identical to that of the cytochrome P450 component of the CYP1alpha, the renal form of the enzyme, and appears to be a product of the same gene. CYP1alpha messenger RNA (mRNA) and 1alpha-hydroxylase enzyme activity were detected in two (SW 900, SK-Luci-6) of a series of five nonsmall cell lung carcinoma cell lines. All five lung cell lines were cultured with the same medium under the same conditions, but only two of the five expressed 1alpha-hydroxylase enzyme; two others (WT-E, Calu-1) expressed high levels of the reciprocally regulated enzyme, 25-hydroxyvitamin D3-24-hydroxylase, with its specific cytochrome P450 component, CYP24. Although under basal conditions the lung cell line SW 900 expressed only CYP1alpha and showed 1alpha-hydroxylase enzyme activity, when treated with small concentrations of 1alpha,25-dihydroxyvitamin D3 or high concentrations of 25-hydroxyvitamin D3, it began to express CYP24 and exhibit 24-hydroxylase enzyme activity. Somewhat surprisingly, SW 900 cells still had detectable CYP1alpha mRNA some 24 h after vitamin D treatment despite the fact that 1alpha-hydroxylase enzyme activity was unmeasurable. These data are consistent with the emerging hypothesis that vitamin D through its active form does not directly turn off CYP1alpha mRNA production but, rather, strongly stimulates CYP24, thereby masking CYP1alpha activity. The factor(s) responsible for the basal expression of CYP1alpha in SW 900 and SK-Luci-6 is currently unknown.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1999

Echolocation behaviour and prey-capture success in foraging bats: laboratory and field experiments on Myotis daubentonii.

During prey-capture attempts, many echolocating bats emit a 'terminal buzz', when pulse repetition rate is increased and pulse duration and interpulse interval are shortened. The buzz is followed by a silent interval (the post-buzz pause). We investigated whether variation in the structure of the terminal buzz, and the calls and silent periods following it, may provide information about whether the capture attempt was successful and about the size of prey detected - detail that is valuable in studies of habitat use and energetics. We studied the trawling bat Myotis daubentonii. The time between the first call of the approach phase and the end of the terminal phase was not related to prey size in the laboratory. The last portion of the terminal buzz (buzz II) was shortened or omitted during aborted capture attempts. Both in the laboratory and in the field, the mean interpulse interval immediately after the terminal buzz (post-buzz interpulse interval) was longer in successful captures than in unsuccessful attempts. In the laboratory, the post-buzz pause was longer after successful captures than for unsuccessful attempts, and the minimum frequency of the first search-phase call emitted after the buzz (Fmin) was higher than that of the last such call prior to the buzz. These effects were not apparent in field data. Both in the laboratory (85%) and in the field (74%), significant discrimination between successful and unsuccessful capture attempts was possible when the duration of the post-buzz pause, post-buzz interpulse interval and Fmin were entered into a discriminant analysis. Thus, variation in the echolocation calls of bats during prey-capture attempts can reveal substantial information about capture success and prey size.

Animals↗