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Biomedical subjects

G Jones

Publications and source records attributed to G Jones.

At least 163 records · Page 9Linked to original sources
PubMed1999

Scaling of echolocation call parameters in bats.

I investigated the scaling of echolocation call parameters (frequency, duration and repetition rate) in bats in a functional context. Low-duty-cycle bats operate with search phase cycles of usually less than 20 %. They process echoes in the time domain and are therefore intolerant of pulse-echo overlap. High-duty-cycle (>30 %) species use Doppler shift compensation, and they separate pulse and echo in the frequency domain. Call frequency scales negatively with body mass in at least five bat families. Pulse duration scales positively with mass in low-duty-cycle quasi-constant-frequency (QCF) species because the large aerial-hawking species that emit these signals fly fast in open habitats. They therefore detect distant targets and experience pulse-echo overlap later than do smaller bats. Pulse duration also scales positively with mass in the Hipposideridae, which show at least partial Doppler shift compensation. Pulse repetition rate corresponds closely with wingbeat frequency in QCF bat species that fly relatively slowly. Larger, fast-flying species often skip pulses when detecting distant targets. There is probably a trade-off between call intensity and repetition rate because 'whispering' bats (and hipposiderids) produce several calls per predicted wingbeat and because batches of calls are emitted per wingbeat during terminal buzzes. Severe atmospheric attenuation at high frequencies limits the range of high-frequency calls. Low-duty-cycle bats that call at high frequencies must therefore use short pulses to avoid pulse-echo overlap. Rhinolophids escape this constraint by Doppler shift compensation and, importantly, can exploit advantages associated with the emission of both high-frequency and long-duration calls. Low frequencies are unsuited for the detection of small prey, and low repetition rates may limit prey detection rates. Echolocation parameters may therefore constrain maximum body size in aerial-hawking bats.

Animals↗
PubMed1999

Domiciliary midwifery support in high-risk pregnancy incorporating telephonic fetal heart rate monitoring: a health technology randomized assessment.

We conducted a health technology assessment of the care of women with high-risk pregnancies in the South Wales valleys. Women in the control arm were intended to receive conventional care with standard midwifery visits. Women in the intervention arm received additional or longer visits and domiciliary fetal heart rate telemonitoring. Eighty-one mothers were randomized. There were significant differences in midwifery intervention resources between domiciliary and control groups, with the former receiving a mean of 3.7 visits lasting 33.5 min, compared with 1.4 visits lasting 12.8 min for the latter. There were slightly more spontaneous labours and fewer Caesarean sections in the domiciliary group. Maternal satisfaction and anxiety were high in both groups. Domiciliary care increased the service costs by 21.02 Pounds per woman in terms of extra midwife travel and visiting time, and by a further 18.38 Pounds per woman in home monitoring equipment costs. This, however, was more than offset by health service savings from fewer clinic visits (35.60 Pounds) and fewer clinic ultrasound scans (9.01 Pounds). Adding the reductions in lost productivity to women and their partners (34.51 Pounds) suggests that domiciliary care was cheaper than conventional care, even if it did not greatly reduce inpatient days (a reduction nonetheless saving 184.24 Pounds). While clinical processes were similar in both groups, there were useful practical advantages and savings for patients and the health service from the domiciliary intervention.

Anxiety↗
PubMed1999

Metabolic acidosis and coma following a severe acetaminophen overdose.

OBJECTIVE: To report a case of metabolic acidosis and coma in a severe acetaminophen overdose. CASE SUMMARY: A 29-year-old white woman was admitted to the emergency department with a diminished level of consciousness and metabolic acidosis. The toxicology screen revealed a serum acetaminophen concentration of 1072 microg/mL, and she was consequently treated with intravenous acetylcysteine. Despite the elevated concentration, the patient did not manifest signs of hepatotoxicity. DISCUSSION: Metabolic acidosis and coma are rare manifestations in acetaminophen overdoses. In published case reports, severe acetaminophen ingestion independently causes metabolic acidosis and coma in the absence of hepatotoxicity. The mechanism by which metabolic acidosis occurs is not clearly defined. Studies conducted on animals demonstrated that in severe overdoses, acetaminophen may cause lactic acidosis by inhibiting mitochondrial respiration. The mechanism by which acetaminophen can cause coma is still unknown. CONCLUSIONS: Severe acetaminophen overdoses can independently cause metabolic acidosis and coma in the absence of hepatotoxicity.

Acetaminophen↗
PubMed1999

Maternal smoking during pregnancy, growth, and bone mass in prepubertal children.

There have been no studies of smoking during pregnancy and bone mineralization in children. The objective of this population-based longitudinal study was to determine whether maternal smoking during pregnancy is associated with bone mass and other growth variables in prepubertal children. We studied 330 8-year-old male and female children representing 47% of those who originally took part in a study of risk factors for Sudden Infant Death Syndrome in 1988. The main outcome measures were bone mineral density measured by a Hologic QDR2000 densitometer: birth weight, placental weight, height, and weight. Maternal smoking during pregnancy was associated with deficits in growth with these children having lower height (-1.53 cm, 95% confidence interval [CI] -3.03 to -0.03) and a trend to lower weight (-1.35 kg, 95% CI -2.75 to 0.11) at age 8. Furthermore, there was a disproportionate deficit in bone mass such that those children whose mothers smoked during pregnancy had lower size adjusted bone mass at the lumbar spine (-0.019 g/cm2, 95% CI -0.033 to -0.005) and femoral neck (-0.018 g/cm2, 95%CI -0.034 to -0.002) but not total body (-0.005 g/cm2, 95% CI -0.015 to 0.005). This association was only present for children born at term. Mothers who smoked during pregnancy also had lower placental weight (- 56 g, 95% CI -95 to -17), and further adjustment for placental weight led to nonsignificant results for smoking with both growth and bone parameters, suggesting that these associations may be mediated through placental size and function. Maternal smoking habit in 1996 was not significantly associated with bone mass at any site. In conclusion, this study has demonstrated a long-term negative association between maternal smoking during pregnancy and both growth and bone mass in children born at term, and suggests that the timing of exposure rather than the dose or duration is critical. If these associations are present in other populations and they persist until the attainment of peak bone mass, then our findings suggest that osteoporosis prevention programs should start very early in the life cycle.

Birth Weight↗
PubMed1999

A cross-sectional study of smoking and bone mineral density in premenopausal parous women: effect of body mass index, breastfeeding, and sports participation.

The objective of this cross-sectional study was to describe the relationship between cigarette smoking, effect modifiers, and bone density in premenopausal parous women. We studied a sample of 276 women (mean age 33 years) from Southern Tasmania. The study factors were cigarette smoking, body mass index (BMI), sports participation, and breastfeeding history. Bone mineral density was measured utilizing an Hologic QDR 2000 densitometer and converted to Z scores using the group mean and variance. There were 118 current smokers and 158 nonsmokers. Smokers had lower bone mass at all sites (femoral neck, -0.32 SD, 95% confidence interval [CI] -0.60 to -0. 04; lumbar spine, -0.49 SD, 95% CI -0.76 to -0.22; total body, -0.40 SD, 95% CI -0.66 to -0.14). Stratifying by BMI revealed that this association was only present, but greater in magnitude, for those with a BMI <25 kg/m2. Smokers who had breastfed at least one child had an additional deficit in bone mass (femoral neck, -0.48 SD, 95% CI -0.89 to -0.07; lumbar spine, -0.39 SD, 95% CI -0.80 to 0.02; total body, -0.37 SD, 95% CI -0.77 to 0.06) while smokers who took part in competitive sport had significant increments in bone mass (femoral neck, 0.74 SD, 95% CI 0.31 to 1.17; lumbar spine, 0.48 SD, 95% CI 0.03 to 0.93; total body, 0.42 SD, 95% CI 0.00 to 0.84). Neither of these two associations were present in nonsmokers. In conclusion, current smoking was associated with substantial deficits in bone mass in our sample of women, particularly those with a BMI <25 kg/m2. In addition, smoking may prevent the usual postweaning recovery phase of bone after breastfeeding while sports participation may offset the negative effect of smoking on bone mass. These observations need to be confirmed in longitudinal studies but they imply that past studies of smoking in this age group may have missed important associations as they did not consider possible effect modifiers.

Body Mass Index↗
PubMed1999

Low bone mass in premenopausal parous women: identification and the effect of an information and bone density feedback program.

The aims of this study of premenopausal parous women were to determine whether low bone mass could be accurately identified by clinical risk factors and to describe the effect of an information and bone mineral density (BMD) feedback program on lifestyle behavior. The subjects were a convenience sample of 271 women who took part in a cohort study of cot death in 1988, and in a population-based study of the determinants of bone mass in 1996. These subjects were provided with BMD feedback according to their T-score. Those with a score < -1.0 at either the femoral neck or lumbar spine were sent a letter indicating that their BMD was low (n = 72), whereas those scoring above -1.0 at both sites (n = 199) were told that their BMD was normal. Both groups were given a comprehensive osteoporosis information leaflet. In late 1997 we were able to contact 256 subjects (95%). In logistic regression, the presence or absence of low BMD was correctly classified in 79% of cases (p < 0.0001) by a model containing body mass index, fracture history, smoking, breastfeeding history, and sports participation. The model had poor sensitivity (38%) but high specificity (93%). At follow-up, those with low BMD had similar smoking cessation rates (16 vs 17%, p = 0.93) but higher rates of increased calcium intake (61 vs 9%), calcium supplement use (39 vs 4%), and increased physical activity (41 vs 17%) (all p < 0.001) in comparison with those with normal BMD. We conclude that a feedback program can alter self-reported behavior in young women for at least 12 mo and that the magnitude of effect is greatest in those with low BMD. Identification of these subjects by clinical risk factors is good but suboptimal, suggesting that measurement of BMD may be necessary to target most accurately and effectively those at highest risk.

Adult↗
PubMed1999

Magnetoencephalographic patterns of epileptiform activity in children with regressive autism spectrum disorders.

BACKGROUND: One-third of children diagnosed with autism spectrum disorders (ASDs) are reported to have had normal early development followed by an autistic regression between the ages of 2 and 3 years. This clinical profile partly parallels that seen in Landau-Kleffner syndrome (LKS), an acquired language disorder (aphasia) believed to be caused by epileptiform activity. Given the additional observation that one-third of autistic children experience one or more seizures by adolescence, epileptiform activity may play a causal role in some cases of autism. OBJECTIVE: To compare and contrast patterns of epileptiform activity in children with autistic regressions versus classic LKS to determine if there is neurobiological overlap between these conditions. It was hypothesized that many children with regressive ASDs would show epileptiform activity in a multifocal pattern that includes the same brain regions implicated in LKS. DESIGN: Magnetoencephalography (MEG), a noninvasive method for identifying zones of abnormal brain electrophysiology, was used to evaluate patterns of epileptiform activity during stage III sleep in 6 children with classic LKS and 50 children with regressive ASDs with onset between 20 and 36 months of age (16 with autism and 34 with pervasive developmental disorder-not otherwise specified). Whereas 5 of the 6 children with LKS had been previously diagnosed with complex-partial seizures, a clinical seizure disorder had been diagnosed for only 15 of the 50 ASD children. However, all the children in this study had been reported to occasionally demonstrate unusual behaviors (eg, rapid blinking, holding of the hands to the ears, unprovoked crying episodes, and/or brief staring spells) which, if exhibited by a normal child, might be interpreted as indicative of a subclinical epileptiform condition. MEG data were compared with simultaneously recorded electroencephalography (EEG) data, and with data from previous 1-hour and/or 24-hour clinical EEG, when available. Multiple-dipole, spatiotemporal modeling was used to identify sites of origin and propagation for epileptiform transients. RESULTS: The MEG of all children with LKS showed primary or secondary epileptiform involvement of the left intra/perisylvian region, with all but 1 child showing additional involvement of the right sylvian region. In all cases of LKS, independent epileptiform activity beyond the sylvian region was absent, although propagation of activity to frontal or parietal regions was seen occasionally. MEG identified epileptiform activity in 41 of the 50 (82%) children with ASDs. In contrast, simultaneous EEG revealed epileptiform activity in only 68%. When epileptiform activity was present in the ASDs, the same intra/perisylvian regions seen to be epileptiform in LKS were active in 85% of the cases. Whereas primary activity outside of the sylvian regions was not seen for any of the children with LKS, 75% of the ASD children with epileptiform activity demonstrated additional nonsylvian zones of independent epileptiform activity. Despite the multifocal nature of the epileptiform activity in the ASDs, neurosurgical intervention aimed at control has lead to a reduction of autistic features and improvement in language skills in 12 of 18 cases. CONCLUSIONS: This study demonstrates that there is a subset of children with ASDs who demonstrate clinically relevant epileptiform activity during slow-wave sleep, and that this activity may be present even in the absence of a clinical seizure disorder. MEG showed significantly greater sensitivity to this epileptiform activity than simultaneous EEG, 1-hour clinical EEG, and 24-hour clinical EEG. The multifocal epileptiform pattern identified by MEG in the ASDs typically includes the same perisylvian brain regions identified as abnormal in LKS. When epileptiform activity is present in the ASDs, therapeutic strategies (antiepileptic drugs, steroids, and even neurosurgery) aimed at its control can lead to a significa

Autistic Disorder↗
PubMed1999

Tyramide signal amplification (TSA)-FISH applied to mapping PCR-labeled probes less than 1 kb in size.

Tyramide signal amplification (TSA)-FISH was used to map one mouse and two human DNA probes of less than 1 kb in size. The two human probes were 319 and 608 bp, and the mouse probe was 855 bp. Probes, made from PCR products, were labeled by incorporating biotin-11-dUTP (human) and biotin-16-dUTP (mouse) during PCR amplification. Signals were readily observed in both interphase and metaphase cells following TSA-FISH for all three genes, whereas conventional FISH experiments produced no signals. The two human ATP-binding cassette (ABC) genes, EST883227 (GenBank Accession No. AA243820) and EST990006 (GenBank Accession No. AA348546), mapped to human chromosomes 7p21 and 17q25. The mouse gene, cmyc (exon 2) mapped to band D2 of mouse chromosome 15. These findings demonstrate the ability of this technique to map small probes (PCR products and expressed sequence tags) of less than 1 kb through highly increased signal amplification.

Animals↗
PubMed1999

Integration of preoperative and intraoperative functional brain mapping in a frameless stereotactic environment for lesions near eloquent cortex. Technical note.

The authors present a method of incorporating preoperative noninvasive functional brain mapping data into the frameless stereotactic magnetic resonance (MR) imaging dataset used for image-guided resection of brain lesions located near eloquent cortex. They report the use of functional (f)MR imaging and magnetic source (MS) imaging for preoperative mapping of eloquent cortex in difficult cases of brain tumor resection such as those in which there are large expansive masses or in which reoperations are required and the anatomy is distorted from prior treatments. To correlate methods of preoperative and intraoperative mapping localization directly, the authors have developed techniques of importing preoperative MS and fMR imaging data into an image-guided frameless stereotactic computer workstation. The data appear as a seamless overlay on the same preoperative volumetric MR imaging dataset used for stereotactic guidance during the operation. Intraoperatively identified functional locations mapped by cortical stimulation are recorded as digitally registered points. This approach should prove useful in assessing the accuracy and reliability of various preoperative functional brain mapping techniques.

Adult↗
PubMed1999

Dental treatment of patients with neurodegenerative disease.

Neurodegenerative disorders are among the most challenging and devastating illnesses in medicine. A heterogeneous group of chronic and progressive diseases, they include Alzheimer's, Parkinson's, and Huntington's diseases. Dentists faced with patients affected by one of these disorders are confronted with the major problems of cognition, mobility, and behaviour, as well as of dental maintenance. While treatment of patients with progressive neurodegeneration remains daunting, increased knowledge of the aetiology and pathogenesis of these diseases has provided new opportunities and a new understanding of their treatment needs. In this article, we briefly describe the effects of ageing on the brain, and introduce two of the major neurodegenerative disorders, Alzheimer's and Parkinson's diseases. The dental problems associated with these conditions include a decrease in oral hygiene, difficulty in controlling and retaining dentures, and purposeless chewing. Medications can result in xerostomia and consequent root caries and recurrent decay. Where possible, individuals with neurodegenerative disorders should always be treated by the same dentist.

Aging↗
PubMed1998

Transcription of the juvenile hormone esterase gene under the control of both an initiator and AT-rich motif.

The binding of transcription factors to the core promoter of the juvenile hormone esterase gene was functionally characterized using both a cell-free in vitro transcription functional assay and a cell transfection assay. A core JHE promoter (-61 to +28 bp relative to transcription start site) supported faithful transcription from the in vivo transcription start site. The nuclear extracts from the Sf9 insect cell line that provided transcription from that template also bound to that template as a probe in gel-mobility shift assays. Deletion or transversion of the initiator-binding motif (-1 to +4 bp) abolished detectable transcription either in vitro or in transfected cells. An AT-rich motif (ATATAT; -28 to -23 bp) serves another transcription factor-binding site. Mutation of the AT-rich motif to a canonical TATA-box preserved transcription, while either its deletion or complete transversion abolished or significantly reduced detectable transcriptional activity. These results indicate that, under these conditions, the functional operation of this core promoter approaches that of a composite promoter in which both the TATA- and initiator-binding protein complexes are necessary, even for basal transcription. On the other hand, these debilitating mutations to either the TATA box or initiator motif did not prevent the ability of the corresponding gel-shift competitive probes to compete with the wild-type promoter for binding by the transcription factors. Even a double transversion of both the AT-rich motif and the initiator-binding motif was able to competitively displace the protein complex that bound to the labelled wild-type probe. These data strongly indicate the presence of (an) additional core-promoter-associated transcription factor(s) (that is not the 'downstream element') that contact(s) the AT-binding complex and/or initiator-binding factor with sufficient avidity to remove them from binding to the competing wild-type promoter sequence.

Animals↗
PubMed1998

Agrin can mediate acetylcholine receptor gene expression in muscle by aggregation of muscle-derived neuregulins.

The neural isoforms of agrin can stimulate transcription of the acetylcholine receptor (AChR) epsilon subunit gene in electrically active muscle fibers, as does the motor neuron upon the formation of a neuromuscular junction. It is not clear, however, whether this induction involves neuregulins (NRGs), which stimulate AChR subunit gene transcription in vitro by activating ErbB receptors. In this study, we show that agrin- induced induction of AChR epsilon subunit gene transcription is inhibited in cultured myotubes overexpressing an inactive mutant of the ErbB2 receptor, demonstrating involvement of the NRG/ErbB pathway in agrin- induced AChR expression. Furthermore, salt extracts from the surface of cultured myotubes induce tyrosine phosphorylation of ErbB2 receptors, indicating that muscle cells express biological NRG-like activity on their surface. We further demonstrate by RT-PCR analysis that muscle NRGs have Ig-like domains required for their immobilization at heparan sulfate proteoglycans (HSPGs) of the extracellular matrix. In extrasynaptic regions of innervated muscle fibers in vivo, ectopically expressed neural agrin induces the colocalized accumulation of AChRs, muscle-derived NRGs, and HSPGs. By using overlay and radioligand-binding assays we show that the Ig domain of NRGs bind to the HSPGs agrin and perlecan. These findings show that neural agrin can induce AChR subunit gene transcription by aggregating muscle HSPGs on the muscle fiber surface that then serve as a local sink for focal binding of muscle-derived NRGs to regulate AChR gene expression at the neuromuscular junction.

Agrin↗
PubMed1998

Information technology. The bug stops here.

The millennium bug arises because up to the 1980s computers were programmed to represent years by the last two digits only. So, when the millennium arrives, programmes which represent the year 2000 as 00 will be unable to make the transition from 1999 into the 21st century. Such programs have been written into microchips, hardware and software. The problem is not restricted to computers, but extends to systems that rely on embedded chips, such as air conditioning, lifts, lighting, security and electro-medical equipment. The potential catastrophic consequences for patient care and administration are clear, and raise liability issues of which NHS managers need to be aware.

Chronology as Topic↗
PubMed1998

Mouse P450RAI (CYP26) expression and retinoic acid-inducible retinoic acid metabolism in F9 cells are regulated by retinoic acid receptor gamma and retinoid X receptor alpha.

We have cloned a mouse cDNA homolog of P450RAI, a cytochrome P450 belonging to a new family (CYP26), which has previously been isolated from zebrafish and human cDNAs and found to encode a retinoic acid-inducible retinoic acid hydroxylase activity. The cross-species conservation of the amino acid sequence is high, particularly between the mouse and the human enzymes, in which it is over 90%. Like its human and zibrafish counterparts, the mouse P450RAI cDNA catalyzes metabolism of retinoic acid into 4-OH-retinoic acid, 4-oxo-retinoic acid, 18-OH-retinoic acid, and unidentified water-soluble metabolites when transfected into COS-1 cells. Retinoic acid-inducible retinoic acid metabolism has previously been observed in F9 murine embryonal carcinoma cells and some derivatives lacking retinoid receptors. We were interested in determining whether P450RAI could be responsible for retinoic acid metabolism in F9 cells and in studying the effect of retinoid receptor ablation on P450RAI expression. In wild-type F9 cells and derivatives lacking RAR gamma, RAR alpha, and/or RXR alpha, we observed a direct relationship between the level of retinoic acid metabolic activity and retinoic acid-induced P450RAI mRNA. These experiments, as well as others using synthetic receptor subtype-specific retinoids, suggest that the RAR gamma and RXR alpha receptors mediate the effects of retinoic acid on the expression of the P450RAI gene.

Amino Acid Sequence↗
PubMed1998

Dorset and Thule divergence from East Central Asian roots.

The history of the immigration of East Asians to America during the last glacial period remains controversial. In an attempt to add critical data to this problem, a large sample of whole teeth derived from Southeast Asian, Mongolian, Thule, Western Inuit, and pre-Inca (Huari) people was quantified (N = 4,507 teeth from 495 individuals; approximately 30 variables per tooth). Multivariate analysis helped establish that all Native Americans were likely derived from one ancient, extinct population that resided in the region of Mongolia (east Central Asia), and that Mongolians and Southeast Asians are two independent groups. A controversial and enigmatic Central Canadian Arctic "Thule culture Inuit" group on Southampton Island that survived until 1902 was identified as a relic, mainly Paleoeskimo Dorset community. Surprisingly, there was little, or no, indication of Dorset-to-Thule gene flow. Cumulatively, the data suggest that a small population of Paleoindian founders remained resident in Beringia, may have blocked further immigration, and were the antecedents to the Thule/Inuit. With the confluence of the Arctic and Pacific oceans at the breakup of Beringia, the resulting increased availability of marine animal food sources allowed this population to increase in size and expand throughout the eastern Arctic.

Arctic Regions↗
PubMed1998

MRI of hyperpolarized 3He gas in human paranasal sinuses.

In this study, MRI of hyperpolarized 3He gas in human paranasal sinuses is presented. Helium images were obtained at 1.5 T, using a surface coil and a 2D, fast gradient-echo sequence with a nominal constant flip angle of 12 degrees. Coronal images of 20-mm thick slices were generated and compared with proton images of the corresponding sections. The images enable visualization of the paranasal sinuses and the nasal cavity, suggesting a potential use of this method not only in identifying the anatomical configuration of these pneumatic spaces, but also in assessing sinus ventilation.

Adult↗
PubMed1998

GENFOLD: a genetic algorithm for folding protein structures using NMR restraints.

We report the development and validation of the program GENFOLD, a genetic algorithm that calculates protein structures using restraints obtained from NMR, such as distances derived from nuclear Overhauser effects, and dihedral angles derived from coupling constants. The program has been tested on three proteins: the POU domain (a small three-helix DNA-binding protein), bovine pancreatic trypsin inhibitor (BPTI), and the starch-binding domain from Aspergillus niger glucoamylase I, a 108-residue beta-sheet protein. Structures were calculated for each protein using published NMR restraints. In addition, structures were calculated for BPTI using artificial restraints generated from a high-resolution crystal structure. In all cases the fittest calculated structures were close to the target structure, and could be refined to structures indistinguishable from the target structures by means of a low-temperature simulated annealing refinement. The effectiveness of the program is similar to that of distance geometry and simulated annealing methods, and it is capable of using a very wide range of restraints as input. It can thus be readily extended to the calculation of structures of large proteins, for which few NOE restraints may be available.

Algorithms↗