Search PubMed⌕ Search

Biomedical subjects

P Schofield

Publications and source records attributed to P Schofield.

At least 73 records · Page 4Linked to original sources
PubMed1995

Growth factors and apoptosis in development. The role of insulin like growth factor I and TGFbeta1 in regulating cell growth and cell death in a human teratocarcinoma derived cell line.

The balance between different cell populations in the developing organism is controlled by regulating the rates of multiplication, differentiation or death of its constituent cells. The human teratocarcinoma derived cell line Tera 2, which in several aspects mirrors early embryonic cells, can be induced to undergo programmed cell death (apoptosis) by depriving cell cultures of serum. This study demonstrates that this process can be reversed by replacing serum with physiological concentrations of insulin like growth factor I (IGF I). As a result, IGF I enhances the rate of Tera 2 cell proliferation in serum free medium. In contrast, Transforming Growth Factor beta1 did not exert any effect on growth or apoptosis in Tera 2 cells. The results indicate that one effect of growth factors on pluripotential cells is to regulate the balance between cell proliferation and cell death.

Apoptosis↗
PubMed1994

Exclusion of close linkage of bipolar disorder to the Gs-alpha subunit gene in nine Australian pedigrees.

Growing evidence suggests that guanine nucleotide binding proteins (G proteins) may be involved in both the pathogenesis and treatment of bipolar affective disorder. Both overactive G proteins and increased levels of the alpha subunit of the stimulatory form (Gs-alpha) have been demonstrated in peripheral leucocytes of manic patients while an increase of Gs-alpha subunit levels has also been found in a postmortem study of bipolar disorder. The function of Gs and Gi alpha subunits has now been shown to be affected by lithium. The present study aimed to determine whether bipolar affective disorder was linked to the Gs-alpha subunit gene which has been mapped to chromosomal region 20q13.2. Linkage analysis utilized the PCR amplification of a portion of the Gs-alpha gene that contains a dinucleotide repeat (CA repeat) polymorphism. Linkage of bipolar disorder and recurrent depression to the Gs-alpha subunit gene was tested using a series of autosomal dominant and recessive models with varying penetrance levels. Additionally, linkage was examined using a series of levels of definitions of affective illness. Close linkage to the Gs-alpha subunit gene was strongly excluded using each model and definition. Thus, our study indicates that a genetic defect in the Gs-alpha subunit gene is unlikely to be the cause of bipolar disorder.

Adolescent↗
PubMed1994

A missense mutation in the gene encoding the alpha 1 subunit of the inhibitory glycine receptor in the spasmodic mouse.

Hereditary hyperekplexia, an autosomal dominant neurologic disorder characterized by an exaggerated startle reflex and neonatal hypertonia, can be caused by mutations in the gene encoding the alpha 1 subunit of the inhibitory glycine receptor (GLRA1). Spasmodic (spd), a recessive neurologic mouse mutant, resembles hyperekplexia phenotypically, and the two disease loci map to homologous chromosomal regions. Here we describe a Glra1 missense mutation in spd that results in reduced agonist sensitivity in glycine receptors expressed in vitro. We conclude that spd is a murine homologue of hyperekplexia and that mutations in GLRA1/Glra1 can produce syndromes with different inheritance patterns.

Amino Acid Sequence↗
PubMed1994

Whole body composition and regional bone mass in women with insulin-dependent diabetes mellitus.

OBJECTIVE: Reduced bone mass has been reported in adult patients with insulin-dependent diabetes mellitus but there are few data on bone density in the axial skeleton or on whole body composition in this group. The aim of this study was to determine whether whole body and regional bone mass are normal in middle-aged women with insulin-dependent diabetes mellitus. DESIGN: Total and regional bone mass were measured in 24 post-menopausal women aged 43-69 years (mean 56.3) with insulin-dependent diabetes, recruited during routine clinic attendance. Results were compared with those obtained from 24 age and weight-matched community-based post-menopausal women. MEASUREMENTS: Whole body bone mineral content and bone mass in the lumbar spine and femoral neck were measured by dual energy X-ray absorptiometry on a Lunar DPX. RESULTS: Whole body bone mineral content was significantly lower in the diabetic women than in community-based controls (P = 0.02). There was no significant difference between the two groups in whole body bone density or lumbar spine bone density. Mean bone density in the femur was lower in the patient group at all sites assessed (femoral trochanter P = 0.003, femoral neck, P = 0.057). Values for all regional bone density measurements in the diabetic women were within the Lunar reference range (mean +/- 2 SD) and at all sites the mean value was close to 100% of the sex and age-matched reference value. There was no correlation between duration or control of diabetes and bone mass at any site. CONCLUSIONS: Insulin-dependent diabetes mellitus in middle-aged women is associated with small reductions in total body bone mineral content and in femoral bone density; the clinical significance of these findings in terms of subsequent fracture risk remains to be established. No evidence was found in this study for a reduction in whole body or lumbar spine bone density.

Adult↗
PubMed1994

Kinetics of fiber digestion from in vitro gas production.

In vitro gas production, measured by computer-interfaced pressure sensors, was used to follow the digestion of a crystalline processed cellulose, a bacterial cellulose, and mixtures of these substrates by mixed ruminal bacteria. A first-order, substrate limited model (simple exponential with lag) and two bacterial growth models (logistic, Gompertz) were tested to fit these data. No single pool model gave an optimal fit to all substrates, but dual pool versions of both the logistic and Gompertz models fitted the data extremely well. Derivations of these models in the context of gas production are presented. The dual pool version of the exponential model commonly used to analyze fiber digestion was not able to reproduce the slope variations seen with mixed substrates. A modified dual pool logistic equation, with a single lag value, was selected to model the in vitro digestion of these substrates. The model was able to predict adequately both the input composition and the kinetic parameters for a defined mixture and gave a good fit (r2 > .995) to data from all the single and mixed substrates tested. This model may be useful for interpreting gas accumulation from natural feedstuffs.

Animal Feed↗
PubMed1993

IGF2 is parentally imprinted during human embryogenesis and in the Beckwith-Wiedemann syndrome.

The phenomenon of parental imprinting involves the preferential expression of one parental allele of a subset of chromosomal genes and has so far only been documented in the mouse. We show here, by exploiting sequence polymorphisms in exon nine of the human insulin-like growth factor 2 (IGF2) gene, that only the paternally-inherited allele is active in embryonic and extra-embryonic cells from first trimester pregnancies. In addition, only the paternal allele is expressed in tissues from a patient who suffered from Beckwith-Wiedemann syndrome. Thus the parental imprinting of IGF2 appears to be evolutionarily conserved from mouse to man and has implications for the generation of the Beckwith-Wiedemann syndrome.

Alleles↗
PubMed1993

Computerized monitoring of gas production to measure forage digestion in vitro.

The techniques reported in this paper were developed to facilitate the study of the kinetics of forage digestion in vitro by measuring gas production. Fiber disappearance as a measure of the reaction rate has been replaced by the use of computerized pressure sensors to monitor the gaseous products (CO2, CH4) of microbial metabolism. The recording system described requires a computer, pressure sensors, an interface card, and appropriate software to monitor gas production continuously. Several variables, including sample size, inoculum size, vessel size, and type of pressure sensor, have been investigated to determine ranges within which gas production can be measured accurately, and the reproducibility of the results has been established. Because this technique uses small (100-mg) samples, a modified NDF method has been introduced that allows determination of extent of digestion at the end of an incubation in which gas production has been monitored. A strong linear relationship existed between NDF disappearance and gas production.

Acetates↗
PubMed1992

Coronary flow reserve is impaired early after cardiac transplantation.

The highest mortality rate after cardiac transplantation, at present, occurs within the first year after cardiac transplantation. The state of the coronary microcirculation soon after cardiac transplantation has not been previously assessed. We investigated the hypothesis that coronary flow reserve (CFR) is impaired in the early postoperative period after cardiac transplantation. A 3F intracoronary Doppler flow probe was inserted into the left anterior descending coronary artery and maximal coronary flow was assessed using the non-endothelial-dependent vasodilator papaverine. We compared two groups of patients: group A--13 patients studied 3 months after operation; and group B--25 patients studied at a median of 4 years after operation (range 2-8 years) without coronary occlusive disease (COD). CFR was defined as the quotient of maximum hyperaemic to resting velocity (vel). CFR was markedly impaired in group A patients compared with group B (3.3 SEM 0.3 versus 4.2 SEM 0.2, P < 0.01). No significant differences between mean resting or peak velocities, original diagnosis, age, active rejection, blood pressure, lipid levels, ischaemic time, cyclosporin levels or cytomegalovirus (CMV) status were noted. Responses to papaverine in resistance coronary vessels are impaired in the early postoperative period after cardiac transplantation. This is caused by a combination of higher resting flow and lower peak flow in the early group. This impairment of function in the coronary microcirculation may contribute to early graft dysfunction and reflect changes in vascular smooth muscle function leading to the development of COD.

Adult↗
PubMed1992

Routine determination of [18F]-L-6-fluorodopa and its metabolites in blood plasma is essential for accurate positron emission tomography studies.

A batch-contact alumina-extraction method has been used to separate [18F]-L-6-fluorodopa (FD) from its principal metabolite, 3-O-methyl-[18F]-6-fluorodopa (3-OMe-FD), in arterial blood plasma samples collected from subjects pretreated with carbidopa during positron emission tomography (PET) scans. The time course of the metabolite-corrected blood plasma activity is then used as an input function for kinetic analysis of striatal FD uptake. Results obtained from using the batch-contact alumina-extraction method were compared with those from high performance liquid chromatography, and also with those from a chromatographic alumina cartridge technique developed in this laboratory. In 60 human subjects including normal healthy volunteers and patients diagnosed as having a movement disorder, arterial blood plasma samples were collected after FD injection during a two-hour PET scan and analyzed by the batch-contact alumina-extraction method. The activity ratio (metabolites/FD) increased linearly with time for all subjects. However, there was a wide variation in the slope of the plot of the activity ratio (metabolites/FD) versus time among the subjects. No significant linear or curved relationship was observed between the slope and the age of the subject. Separation of FD from its metabolites is therefore necessary for each PET-FD study conducted.

Adsorption↗
PubMed1992

[L-18F-dopa-PET in Parkinson-plus syndromes for the detection of a disordered presynaptic dopaminergic function].

PET examinations using L-18F-DOPA were performed on 14 patients with Parkinsonism-plus syndromes (PPLUS). A rate constant Ki was calculated by a graphical method using an arterial input function. Sequential PET images were obtained and no specific activity was measured both in cortical and cerebellar background regions. These results were compared with those in 20 normal controls and tested for intra- and interobserver variability. All patients with PPLUS showed reduced Ki values with a mean of 0.154 (ml/striatum/min), whereas controls exhibited Ki values with a mean of 0.690 (ml/striatum/min) using cortical background regions. The correlation coefficient was calculated to be r = 0.973 for the intraobserver variability and r = 0.879 for the interobserver variability in controls, and r = 0.989 or = 0.973 in PPLUS, resp. There was no significant difference in the Ki values for cortical and cerebellar background regions (p = 0.1). PET examinations using L-18F-DOPA can reliably assess the extent of nigrostriatal degeneration in vivo. Since this radiotracer binds irreversibly within the striatum PET examinations allow the quantification of a disturbed dopaminergic function which is observer-independent.

Aged↗
PubMed1991

Ultrasonic propagation in slurries.

Experimental measurements have been made of the ultrasonic velocity and attenuation in some simple suspensions of, mainly, silicon carbide in water and in ethylene glycol. These are compared with theoretical predictions based on a novel hydrodynamic model. Predicted ultrasonic velocities are in excellent agreement with the measured values. Predicted and measured ultrasonic attenuations do not agree as well. However, the suspensions give rise to excess attenuations rising to a few hundred nepers per metre and special experimental techniques were needed to measure ultrasonic properties. To predict attenuations to within, say, 20% for mixtures such as these is a major achievement.

Carbon↗
PubMed1991

Development and validation of an instrument to measure satisfaction of participants at breast screening programmes.

A reliable and valid questionnaire has been developed to measure the satisfaction of participants with service offered at mammography screening programmes. The questionnaire measures five specific aspects: convenience and accessibility, staffs' interpersonal skills, information transfer between staff and client, physical surroundings and perceived technical competence of staff. A general satisfaction dimension was also included. Systematic procedures were followed to ensure that the initial pool of items met the criteria for satisfactory content validity. These procedures included extensive literature review and interviews with participants and service providers. Discriminant validity was assessed by a modified Q-sort procedure, where eight expert judges sorted items into relevant dimensions. The sample for other validity and reliability testing consisted of 584 women who were participants at a breast X-ray programme in Melbourne, Australia. Concurrent validity was demonstrated by considering the correlation of the sum of the subscale scores for each respondent with their score on the general subscale (r = 0.76; P less than 0.001). Multiple regression was used to provide further evidence for the discriminant validity of the proposed subscales and support for the multidimensional conceptualism of satisfaction. Scores on the general satisfaction subscale were used as an outcome variable and other subscale scores were predictor variables. All subscale scores significantly contributed to the prediction of satisfaction, over and above that of other subscales (R2 = 0.59). This indicates that these subscales are measuring distinct dimensions of satisfaction. Cronbach's alpha of each subscale was over 0.50, indicating that the subscales are reliable. The instrument is a potentially useful tool for assessing the quality of care at mammographic screening services and could be used routinely by such services to monitor satisfaction.

Australia↗