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Biomedical subjects

G Jones

Publications and source records attributed to G Jones.

At least 127 records · Page 7Linked to original sources
PubMed2000

Birth weight, birth length, and bone density in prepubertal children: evidence for an association that may be mediated by genetic factors.

There is an incomplete understanding of the contribution of early growth to bone accrual in childhood. The aims of this longitudinal study were to examine the association between growth variables at birth, 1 month, and 8 years and bone density in prepubertal children. Weight and length at both birth and 1 month of age were measured in 1988 as part of a prospective study for sudden infant death syndrome. A total of 330 children (47%) and 278 of their mothers were then contacted in 1996 for measurement of anthropometrics and bone density. Birth weight, birth length, and length gain (but not weight gain) in the first month all made significant contributions to areal bone density (BMD, g/cm(2)) at all sites at age 8 even after taking into account subsequent weight and height gain (model R(2) 14-39% depending on variable and site). Adjustment for potential environmental confounders did not alter these findings, however, adjustment for maternal BMD markedly reduced the early life associations (particularly for birth weight). Though early life factors were weakly associated with bone mineral apparent density (BMAD, g/cm(3)) in correlation analysis, subsequent height and weight gain were the only significant independent contributors to BMAD. In conclusion, early life anthropometrics make little contribution to BMAD (other than through their correlation with later growth) but make significant independent contributions to BMD suggesting that the growth trajectory of bone is determined very early in life. In addition, the contribution of body size at birth to bone growth in early life appears to be mediated by genetic factors although it is possible that it may be mediated by poorly measured or as yet unidentified determinants of body size at birth.

Absorptiometry, Photon↗
PubMed2000

Glucose sensor with improved haemocompatibilty.

A new biocompatible copolymer has been synthesised and used in an electrochemical enzyme-based glucose sensor. The copolymer incorporates three segments including a monomer with an electrically neutral phosphorylcholine head group that is able to reject protein adsorption and two segments that increase the affinity to polyurethane substrate. Peel and solution circulation tests showed that this material has high attachment to polyurethane. With the new copolymer as the outermost layer and the polyurethane as the diffusion-limiting membrane, the sensor showed extended linearity up to 50 mM glucose and stable output in bovine serum for 70 h. During in vivo tests, the sensor exhibited a steady current signal and a rapid transient response when the glucose concentration was raised. These results imply that the haemocompatibility of the glucose sensor coated with the new copolymer has been improved, which is crucial for a sensor used for clinical real-time monitoring. The material may also be suitable for application to other implantable devices.

Animals↗
PubMed2000

Maternal diet during pregnancy is associated with bone mineral density in children: a longitudinal study.

OBJECTIVE: To describe the association between maternal diet during the third trimester of pregnancy and bone mass in 8 y-old male and female children. DESIGN: Longitudinal study. SETTING: Southern Tasmania between 1988 and 1996. SUBJECTS: One-hundred and seventy-three 8-y-old male and female children with adequate maternal dietary information taking part in a study of bone mineralization. RESULTS: After adjustment for confounders, femoral neck bone mineral density (BMD) was positively associated with magnesium and phosphorus density of the maternal diet; lumbar spine BMD was positively associated with magnesium, phosphorus and potassium and negatively associated with fat density while total body BMD was positively associated with magnesium, potassium and protein and negatively associated with fat density (all P<0.05). After further adjustment for other significant dietary factors, the only significant remaining associations observed were for phosphorus and fat at the lumbar spine, although the adjusted goodness of fit of the models improved compared to those including one dietary variable. A child in the 'optimal' levels of dietary exposures had significantly higher adjusted BMD at all sites (femoral neck, +5.5%, lumbar spine, +12%, total body, +6.8%). Calcium intake was not associated with BMD at any site, possibly due to a high average intake. CONCLUSIONS: This study reports a substantial association between in utero diet in a well-nourished population and later bone mass in their children. However, it does not allow identification of the dietary components of greatest importance, indicating that these results should be regarded as hypothesis-generating. Further longitudinal studies in other populations are required to confirm that dietary manipulation during pregnancy has a role to play in the early life prevention of osteoporosis.

Bone Density↗
PubMed2000

The high affinity neurotensin receptor gene (NTSR1): comparative sequencing and association studies in schizophrenia.

Neurotensin and its high affinity receptor (NTSR1) localise within dopaminergic neurones in the mesocortical, mesolimbic and nigrostriatal systems and it is now clear that neurotensin can selectively modulate dopaminergic neurotransmission. This has led to the hypothesis that altered neurotensin function contributes to the pathogenesis of schizophrenia and other psychoses. This hypothesis has been supported circumstantially by a number of lines of evidence. (1) Central administration of neurotensin produces effects similar to those produced by the peripheral administration of atypical antipsychotics. (2) Observations of low levels of neurotensin in the CSF of schizophrenics. (3) Reduced numbers of neurotensin receptors in the brains of schizophrenics. Given the above link between neurotensin and dopamine, and the evidence implicating altered neurotensin function in psychosis, we have postulated that DNA sequence variation in neurotensin or its receptors might be associated with schizophrenia. In keeping with this hypothesis, an association has recently been reported between schizophrenia and the gene encoding the neurotensin high affinity receptor (NTSR1). However, caution is required because the associated marker, a tetranucleotide repeat, is located 3 kb away from the 3' end of the gene and there is no evidence that it is functional. Therefore, as a follow-up to our earlier work on neurotensin, we have now sought to test the hypothesis that DNA sequence variants that alter the structure or expression of the NTSR1 gene (VAPSEs) are associated with schizophrenia. However, while we found 14 novel sequence variants in 28 probands with psychosis, none resulted in an amino acid change, and neither direct nor indirect association studies suggested these are involved in susceptibility to schizophrenia.

Brain Chemistry↗
PubMed2000

Genetic variation and population structure in the endangered greater horseshoe bat Rhinolophus ferrumequinum.

Following a dramatic decline last century, the British population of the endangered greater horseshoe bat Rhinolophus ferrumequinum is highly fragmented. To examine the consequences of fragmentation and limited dispersal on patterns of genetic structure and variation, we used microsatellite markers to screen bats from around 50% of the known maternity colonies in Britain, and two areas from continental Europe. Analyses revealed that Welsh and English colonies were genetically isolated. This, and lower variability in Britain than north France, may result from either genetic drift, or the species' colonization history. Gene flow among most neighbouring colonies was not generally restricted, with one exception. These findings have important implications for the ongoing conservation management of this species.

Animals↗
PubMed2000

Vaccines for the control of HIV/AIDS.

This review discusses the feasibility of an HIV vaccine and describes the history, efficacy and potential to succeed of old and new vaccine concepts.

AIDS Vaccines↗
PubMed2000

Inhibition of delayed rectifier K+ conductance in cultured rat cerebellar granule neurons by activation of calcium-permeable AMPA receptors.

Activation of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors in cerebellar granule cells during perforated-patch whole-cell recordings activated an inward current at negative voltages which was followed, after a delay, by the inhibition of an outward potassium current at voltages positive to -20 mV. The activated inward current was inwardly rectifying suggesting that the AMPA receptors were Ca2+-permeable. This was confirmed by direct measurements of intracellular calcium where Ca2+ rises were seen following AMPA receptor activation in Na+-free external solution. Ca2+ rises were equally large in the presence of 100 microM Cd2+ to block voltage-gated Ca2+ channels. Specific voltage-protocols, allowing selective activation of the delayed rectifier potassium current (KV) and the transient A current (KA), showed that kainate inhibited KV, but not to any great extent KA. The inhibition of KV was blocked by the AMPA receptor antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) and was no longer observed when the KV current was abolished with high concentrations of Ba2+. The responses to kainate were not altered by pre-treating the cells with pertussis toxin, suggesting that the AMPA receptor stimulation of the G-protein Gi cannot account for the effects observed. Replacing extracellular Na+ with choline did not alter the inhibition of KV by kainate, however, removing extracellular Ca2+ reduced the kainate response. The inhibition of KV by kainate was unaffected by the presence of 100 microM Cd2+. The guanylyl cyclase inhibitor, ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one), did not alter kainate inhibition of KV. It is concluded that ion influx (particularly Ca2+ ions) through AMPA receptor channels following receptor activation leads to an inhibition of KV currents in cerebellar granule neurons.

Animals↗
PubMed2000

A role for cytosolic hsp70 in yeast [PSI(+)] prion propagation and [PSI(+)] as a cellular stress.

[PSI(+)] is a prion (infectious protein) of Sup35p, a subunit of the Saccharomyces cerevisiae translation termination factor. We isolated a dominant allele, SSA1-21, of a gene encoding an Hsp70 chaperone that impairs [PSI(+)] mitotic stability and weakens allosuppression caused by [PSI(+)]. While [PSI(+)] stability is normal in strains lacking SSA1, SSA2, or both, SSA1-21 strains with a deletion of SSA2 cannot propagate [PSI(+)]. SSA1-21 [PSI(+)] strains are hypersensitive to curing of [PSI(+)] by guanidine-hydrochloride and partially cured of [PSI(+)] by rapid induction of the heat-shock response but not by growth at 37 degrees. The number of inheritable [PSI(+)] particles is significantly reduced in SSA1-21 cells. SSA1-21 effects on [PSI(+)] appear to be independent of Hsp104, another stress-inducible protein chaperone known to be involved in [PSI(+)] propagation. We propose that cytosolic Hsp70 is important for the formation of Sup35p polymers characteristic of [PSI(+)] from preexisting material and that Ssa1-21p both lacks and interferes with this activity. We further demonstrate that the negative effect of heat stress on [PSI(+)] phenotype directly correlates with solubility of Sup35p and find that in wild-type strains the presence of [PSI(+)] causes a stress that elevates basal expression of Hsp104 and SSA1.

Adenosine Triphosphatases↗
PubMed2000

Measuring blood volume with fluorescent-labeled hydroxyethyl starch.

OBJECTIVES: To develop and evaluate a method for measuring blood volume using the dilution of a fluorescent-labeled hydroxyethyl starch. DESIGN: Laboratory and clinical investigation. SETTING: Biochemistry laboratory at the University of Cardiff. Hematology clinic, surgical ward and intensive care unit of the University Hospital of Wales. PATIENTS: Seventeen patients with suspected polycythemia. Eight patients who had undergone major surgery and/or were receiving intensive postoperative care. INTERVENTIONS: All surgical and postoperative care was provided by clinicians not involved in the study. Patients with suspected polycythemia were referred for blood volume measurement using labeled albumin and red blood cells. MEASUREMENT AND MAIN RESULTS: A proprietary brand of hydroxyethyl starch (Elohaes) was labeled with fluorescein isothiocyanate. Dilution of this compound in vivo was used for measuring blood volume, and the results were compared with those obtained using radiolabeled albumin and the considered criterion, radiolabeled red cells. The elimination of the labeled starch follows the same progress as that of the parent compound, indicating that the fluorescent tag is stable in vivo. The volume of distribution of the labeled starch is 2.5 mL/kg lower than that for labeled albumin (p = .05). Blood volume, measured from the dilution of fluorescent starch, is lower (4.9 mL/kg) than that measured with albumin (p = .048) but higher (6.61 mL/kg) than that measured with red blood cells (p = .0007). This latter difference may be even smaller at marginally higher doses of the fluorescent starch. CONCLUSION: These data support the view that hydroxyethyl starch provides a valid alternative to red cell labels as a means of calculating blood volume in patients. Labeling the starch with a fluorescent marker makes the assay procedure more sensitive and infinitely easier. The dose required is not high enough to affect the hemodynamic status of the patient.

Blood Volume↗
PubMed2000

The effect of sodium citrate in arterial catheters on acid-base and electrolyte measurements.

OBJECTIVE: To compare the effects of heparin or sodium citrate used to anticoagulate indwelling arterial catheters on acid-base and electrolyte measurements. DESIGN: Randomized controlled trial. SETTING: Medical-surgical university-affiliated intensive care unit. SUBJECTS: Twenty patients with indwelling arterial catheters. INTERVENTIONS: Patients were randomly allocated to have ten 1-mL aliquots of blood sampled serially from an arterial catheter maintained with either heparin or sodium citrate. A sample then obtained by arterial puncture provided true measurement values. Acid-base and electrolyte measurements of whole blood were obtained from each sample by means of a Coming 860 analyzer. MEASUREMENTS AND MAIN RESULTS: Contamination with sodium citrate lowered ionized calcium and pH but increased glucose and Pco2. Heparin produced negligible effects on those measurements. When sodium citrate was used, reliable measurements were not obtained for ionized calcium, pH, and glucose, even after 9 mL of blood had been discarded. However, reliable P(CO2) measurements were obtained after 2 mL of blood was discarded. CONCLUSIONS: Sodium citrate used to maintain arterial catheters can contaminate blood samples. The result of that contamination can mimic severe hypocalcemia, metabolic acidosis, and mild hyperglycemia. Failure to recognize the effects of sodium citrate on acid-base and electrolyte measurements may lead to changes in treatment that could affect patient outcome adversely.

Acid-Base Equilibrium↗
PubMed2000

The use of outcome measures to formulate intervention strategies.

OBJECTIVE: To investigate the relative value of the use of open-ended and structured questionnaires in the determination of the most appropriate management of patients in a busy audiological rehabilitation clinic. DESIGN: An open set questionnaire was sent to 56 consecutive patients before clinic attendance, and they were asked to rate the severity of the problems listed on arrival at the clinic. They subsequently were administered the Hearing Disability and Handicap Scale (HDHS), which was not scored until after management decisions had been made. The implications of the results of both questionnaires separately and together for patient management were compared. RESULTS: The Problem Questionnaire highlighted a number of areas in terms of Activity Limitation (Disability) not covered in the HDHS, some of which, such as employment effects, were considered to be of considerable importance to the patients. However, in the field of more general Participation Restriction (Handicap), the structured questionnaire highlighted a number of important areas not volunteered by the patient. CONCLUSION: Although the open-set Problem Questionnaire approach is valid in the domain of Activity Limitation, it needs to be supplemented by an additional measure of Participation Restriction, either open-set or structured, to ensure optimal patient management.

Adult↗
PubMed2000

Using a cognitive architecture to examine what develops.

Different theories of development propose alternative mechanisms by which development occurs. Cognitive architectures can be used to examine the influence of each proposed mechanism of development while keeping all other mechanisms constant. An ACT-R computational model that matched adult behavior in solving a 21-block pyramid puzzle was created. The model was modified in three ways that corresponded to mechanisms of development proposed by developmental theories. The results showed that all the modifications (two of capacity and one of strategy choice) could approximate the behavior of 7-year-old children on the task. The strategy-choice modification provided the closest match on the two central measures of task behavior (time taken per layer, r = .99, and construction attempts per layer, r = .73). Modifying cognitive architectures is a fruitful way to compare and test potential developmental mechanisms, and can therefore help in specifying "what develops."

Adult↗
PubMed2000

Vitamin D deficiency and secondary hyperparathyroidism: clinical and biochemical associations in older non-institutionalised Southern Tasmanians.

AIM: To determine the prevalence and associations of vitamin D (25-OHD) deficiency in a sample of older Tasmanian subjects. METHODS: A cross-sectional survey of: 109 patients with a mean age of 79 years (range 60-101 years) consecutively admitted to a short stay geriatric rehabilitation ward; 52 community dwelling subjects with a mean age of 75 years (range 64-88 years). Subjects answered a questionnaire, had anthropometric measurements and underwent venepuncture. RESULTS: The main outcome measure was 25 hydroxy vitamin D (25-OHD) level with deficiency defined as <28 nmol/L. Vitamin D deficiency was found in 67% and secondary hyperparathyroidism in 49% of the hospitalised group. Vitamin D deficiency was also found in 17% of the community group, in particular one in three residents of Independent Living Units was deficient. Subjects who were deficient were older (80 years vs 76 years [p<0.001]), had lower body mass index (23.7 kg/m2 vs 25.9 kg/m2 [p<0.001]) and had a lower serum albumin (35 gm/L vs 39 gm/L [p<0.001]). Deficient subjects had poorer physical functional status (p=0.02) and lower activity levels (p<0.001) and reported less habitual sun exposure (p<0.001). Biochemical measures such as parathyroid hormone, alkaline phosphatase and calcium were weakly predictive of vitamin D levels. By stepwise multiple regression analysis, the only significant predictors of vitamin D levels were the Frenchay Activity Index, albumin and calcium. CONCLUSION: Vitamin D deficiency and secondary hyperparathyroidism is common in community living older people who are hospitalised in Southern Tasmania and is associated with increasing age, poor physical function and activity and low reported sun exposure.

Activities of Daily Living↗
PubMed2000

Anti-varicella-zoster virus bicyclic nucleosides: replacement of furo by pyrro base reduces antiviral potency.

We have recently reported the discovery of an entirely new category of potent antiviral agents based on novel deoxynucleoside analogues with unusual fluorescent bicyclic furo base moieties. To probe structure-activity relationships and to seek to optimize the properties of the lead compounds, we prepared pyrro analogues of the furo systems. We herein report the synthesis, characterization and antiviral evaluation of these novel compounds.

Antiviral Agents↗
PubMed2000

Acoustic identification of twelve species of echolocating bat by discriminant function analysis and artificial neural networks.

We recorded echolocation calls from 14 sympatric species of bat in Britain. Once digitised, one temporal and four spectral features were measured from each call. The frequency-time course of each call was approximated by fitting eight mathematical functions, and the goodness of fit, represented by the mean-squared error, was calculated. Measurements were taken using an automated process that extracted a single call from background noise and measured all variables without intervention. Two species of Rhinolophus were easily identified from call duration and spectral measurements. For the remaining 12 species, discriminant function analysis and multilayer back-propagation perceptrons were used to classify calls to species level. Analyses were carried out with and without the inclusion of curve-fitting data to evaluate its usefulness in distinguishing among species. Discriminant function analysis achieved an overall correct classification rate of 79% with curve-fitting data included, while an artificial neural network achieved 87%. The removal of curve-fitting data improved the performance of the discriminant function analysis by 2 %, while the performance of a perceptron decreased by 2 %. However, an increase in correct identification rates when curve-fitting information was included was not found for all species. The use of a hierarchical classification system, whereby calls were first classified to genus level and then to species level, had little effect on correct classification rates by discriminant function analysis but did improve rates achieved by perceptrons. This is the first published study to use artificial neural networks to classify the echolocation calls of bats to species level. Our findings are discussed in terms of recent advances in recording and analysis technologies, and are related to factors causing convergence and divergence of echolocation call design in bats.

Acoustics↗
PubMed2000

Characterization of 3-epi-1alpha,25-dihydroxyvitamin D3 involved in 1alpha,25-dihydroxyvitamin D3 metabolic pathway in cultured cell lines.

Using six different cultured cell models representing osteoblast, intestine, kidney and keratinocyte, we have demonstrated that 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) is metabolized into 3-epi-1alpha,25(OH)2D3 in vitamin D-target cells. Although differences existed in the amount of 3-epi-1alpha,25(OH)2D3 formed with different cell types, it was apparent that 1alpha,25(OH)2D3 was subjected to metabolism both through the C24-oxidation and 3-epimerization pathways. Time course and dose response studies showed that the production of 3-epi-1alpha,25(OH)2D3 was enzymatic. It is interesting to note that this epimerization proceeded from 3beta towards 3alpha unidirectionally, and this conversion was not inhibited by ketoconazole. These data suggest that cytochrome P450 related enzymes including the 24-hydroxylase would not affect this reaction. The biological activity of 3-epi-1alpha,25(OH)2D3 was found to be lower than the native 1alpha,25(OH)2D3 in suppressing of proliferation of HL-60 cells, while the affinity of 3-epi-1alpha,25(OH)2D3 for vitamin D-binding protein was 2.5-fold higher than that of 1alpha,25(OH)2D3. The results indicate that 3-epimerization may change the pharmacokinetics and catabolism of 1alpha,25(OH)2D3 in vitamin D-target cells.

Animals↗