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Biomedical subjects

A M Jones

Publications and source records attributed to A M Jones.

At least 37 records · Page 2Linked to original sources
PubMed2002

Mitochondrial involvement in tracheary element programmed cell death.

The mitochondria pathway is regarded as a central component of some types of programmed cell death (PCD) in animal cells where specific signals cause the release of cytochrome c from mitochondria to trigger a proteolytic cascade involving caspases. However, plant cells lack canonical caspases, therefore a role for the mitochondria in programmed cell death in plant cells is not obvious. Using plant cells which terminally differentiate, we provide evidence supporting the involvement of mitochondria in PCD, however the release of cytochrome c is insufficient to trigger the PCD. Prior to execution of cellular autolysis initiated by the rupture of the large central vacuole to release sequestered hydrolases, mitochondria adopt a definable morphology, the inner membrane depolarizes prior to death, and cytochrome c is released from mitochondria. However, PCD can be blocked despite translocation of cytochrome c. These results suggest a role for the mitochondria in this PCD but do not support the current animal model for a causative role of cytochrome c in triggering PCD.

Apoptosis↗
PubMed2002

Prospective, placebo-controlled trial of 5 vs 10 days of oral prednisolone in acute adult asthma.

BACKGROUND: The optimal duration of oral steroid treatment in the management of acute adult asthma is unclear. We prospectively studied the effect of 5 vs. 10 days of oral prednisolone in patients with acute asthma requiring hospital admission. METHODS: Each patient received 40 mg of enteric-coated prednisolone daily for 5 days, followed by 5 days of 40 mg prednisolone daily (n=24) or placebo (n=20). All were given their usual inhaled asthma therapy including inhaled corticosteroids. Patients kept PEF and symptom diaries for 21 days. RESULTS: For the 5-day treatment group mean (95% CI) early morning PEF was 6 (-47,+36) l/min lower to day 21 (P=0.78). There was no evidence of differences in other PEF measures (morning post-bronchodilator, evening or worst of day). One patient in each group had an exacerbation requiring further oral steroids during the 21-day observation period. Asthma symptom scores were worse in the 5-day group on days 6-21 but the significance of this finding was uncertain, as a difference had emerged by day 5 (prior to trial entry). CONCLUSIONS: It may be possible to reduce the standard steroid course to 5 days in acute adult asthma, provided all patients receive inhaled steroids and a personal asthma management plan.

Acute Disease↗
PubMed2002

Running economy is negatively related to sit-and-reach test performance in international-standard distance runners.

The purpose of this study was to investigate the relationship between running economy (RE) and lower body flexibility. Thirty-four international-standard male distance runners (mean +/- s, age 27 +/- 5 years; body mass 64.9 +/- 4.2 kg; VO(2)max 72.8 +/- 3.7 ml x kg(-1) x min(-1)) gave written consent to participate in this study. The subjects performed an incremental treadmill test for the assessment of RE, lactate threshold and VO(2)max, and the sit-and-reach test was used to assess their general lower body and trunk flexibility. Running speeds below the lactate threshold were used to explore the relationship between running economy and sit-and-reach test performance. At 16.0 km x h(-1), the VO(2) was 50.6 +/- 3.7 ml x kg(-1) x min(-1) (range: 44.2 to 57.1 ml x kg(-1) x min(-1)). Pearson product moment correlation coefficients revealed no significant relationships between aerobic demand at 16.0 km x h(-1) and age (r = - 0.19), height (r = 0.15), body mass (r = - 0.18), or VO(2)max (r = - 0.004). However, there was a highly significant relationship between aerobic demand at 16.0 km x h(-1) and the sit-and-reach test score (r = 0.68; p < 0.0001). These results suggest that the least flexible runners are also the most economical. It is possible that stiffer musculotendinous structures reduce the aerobic demand of submaximal running by facilitating a greater elastic energy return during the shortening phase of the stretch-shortening cycle.

Adult↗
PubMed2002

Bioenergetic constraints on tactical decision making in middle distance running.

BACKGROUND: The highest velocity that a runner can sustain during middle distance races is defined by the intersection of the runner's individual velocity-time curve and the distance-time curve. The velocity-time curve is presumably fixed at the onset of a race; however, whereas the race distance is ostensibly fixed, the actual distance-time curve is not. That is, it is possible for a runner to run further than the race distance if he or she runs wide on bends in track races. In this instance, the point of intersection of the individual velocity-time curve and the distance-time curve will move downwards and to the right, reducing the best average velocity that can be sustained for the distance. METHODS: To illustrate this point, the race tactics used by the gold and silver medallists at 800 m and 5000 m in the Sydney Olympics were analysed. The paths taken by the runners were carefully tracked and the total distance they covered during the races and the average velocity they sustained over the distances they actually covered were calculated. RESULTS: In both the Olympic 800 m and 5000 m finals, for example, the winner was not the runner who ran at the highest average velocity in the race. Rather, the winners of these races were able to husband their metabolic resources to better effect by running closer to the actual race distance. CONCLUSIONS: Race results in middle distance running events are dependent not just on the energetic potential of the runners at the start of the race and their strategy for pace allocation, but also on the effect of their tactical approach to positioning on the total distance covered in the race. Middle distance runners should be conscious of minimising the distance covered in races if they wish to optimise their performance.

Decision Making↗
PubMed2002

Increased treatment requirements of patients with cystic fibrosis who harbour a highly transmissible strain of Pseudomonas aeruginosa.

BACKGROUND: A group of patients who harbour the same highly transmissible strain of Pseudomonas aeruginosa were identified at a cystic fibrosis (CF) centre. Isolates of this strain display a number of unusual phenotypic features including resistance to most typical antipseudomonal antibiotics. A study was undertaken to see if there was a difference in treatment requirements between CF patients with chronic infection with their own unique P aeruginosa strains (group 1) and those who harbour a highly transmissible strain (group 2). METHODS: Data on treatment requirements for the year 2000 were collected from the case records of CF patients with chronic P aeruginosa infection who had received inpatient treatment. Patients co-infected with Burkholderia cepacia or other highly transmissible strains of P aeruginosa were excluded. RESULTS: There were 2/56 and 3/22 deaths in groups 1 and 2, respectively; these patients were excluded from the analysis. No difference was found between the two groups for mean age, % predicted forced expiratory volume in 1 second (FEV(1)), % predicted forced vital capacity (FVC), and body mass index. Patients in group 2 had a greater median (range) number of intravenous antibiotic days (60 (17-216) v 33 (4-237) days; p=0.01), inpatient days (39 (7-183) v 16 (1-172) days; p<0.01), and inpatient episodes (3 (1-9) v 2 (1-6); p<0.01), and more respiratory exacerbations (mean (SD) 8.2 (3.4) v 6.1 (3.2); p=0.01). CONCLUSIONS: Patients who harbour the highly transmissible P aeruginosa strain have a greater treatment burden than patients with CF who harbour their own unique strains. These findings support the need for microbiological surveillance for highly transmissible P aeruginosa and the implementation of infection control measures to prevent cross infection.

Adult↗
PubMed2001

Echocardiographic features and outcome of truncus arteriosus diagnosed during fetal life.

There are few data on the outcome of truncus arteriosus when this diagnosis is made during fetal life. Such prognostic information is important to assist parental counseling during pregnancy. This study aimed to analyze, retrospectively, the echocardiographic features and outcome of fetuses with truncus arteriosus. A database of those presenting to a tertiary center for fetal cardiology between 1990 and 1999 was reviewed. Cases in which truncus arteriosus was identified as a firm or differential diagnosis were selected. Outcome data were derived from clinical records, and fetal echocardiograms were reviewed retrospectively. At presentation, truncus arteriosus was firmly diagnosed in 16 patients and was a differential diagnosis in 12. Fourteen of 16 (87%) of the firm diagnoses were correct. There were 17 confirmed cases of truncus arteriosus. Pregnancy was terminated in 4 patients (24%) and there were 13 live births. One child was not actively treated, 4 (31%) died preoperatively, and 8 (61%) underwent surgery. Thirty-day surgical mortality was 2 of 8 (25%). There was 1 late death after cardiac catheterization, and overall survival on an intention-to-treat basis was 5 of 12 (42%). Five of 6 patients with a prenatal truncal valve Doppler velocity above the normal aortic range were found to have postnatal truncal valve stenosis. Two fetuses with stenotic valves died preoperatively with sudden cardiovascular collapse. Counseling of parents for fetuses with truncus arteriosus should include the relatively high nonsurgical mortality as well as surgical results. Elevated prenatal truncal valve Doppler velocity predicts postnatal truncal valve stenosis. Fetuses with truncal valve stenosis may be at risk of early sudden death.

Female↗
PubMed2001

Switch junction sequences in PMS2-deficient mice reveal a microhomology-mediated mechanism of Ig class switch recombination.

Isotype switching involves a region-specific, nonhomologous recombinational deletion that has been suggested to occur by nonhomologous joining of broken DNA ends. Here, we find increased donor/acceptor homology at switch junctions from PMS2-deficient mice and propose that class switching can occur by microhomology-mediated end-joining. Interestingly, although isotype switching and somatic hypermutation show many parallels, we confirm that PMS2 deficiency has no major effect on the pattern of nucleotide substitutions generated during somatic hypermutation. This finding is in contrast to MSH2 deficiency. With MSH2, the altered pattern of switch recombination and hypermutation suggests parallels in the mechanics of the two processes, whereas the fact that PMS2 deficiency affects only switch recombination may reflect differences in the pathways of break resolution.

Adenosine Triphosphatases↗
PubMed2001

Activity analysis of English Premiership rugby football union refereeing.

Little is known about the physiological demands placed on officials during sporting activities. The purpose of this study was to ascertain the movement activities of referees during English Premiership rugby football union matches, and to determine the frequency and duration of these activities. Nine referees who were ranked in the top 20 referees in England were videotaped during a total of 19 matches. During playback of the videotapes, a single observer coded the referees' activities into one of six distinct categories (standing, walking forwards, walking backwards, jogging, running and sprinting) using a computerized video editing system (Observer Video-Pro). The referees were timed over a 20 m distance for the modes of locomotory activity, and the average velocity of the referee for each activity was used to calculate the total distance covered in each mode of activity during matches. The total distance covered during a match was (chi +/- SD) 8581 +/- 668 m. The mean percentage of total playing time spent in each activity was: standing still, 37.0 +/- 11.0%; walking forward, 29.5 +/- 7.2%; walking backward, 9.9 +/- 3.2%; jogging, 12.8 +/- 3.2%; running, 9.8 +/- 2.3%; and sprinting, 1.0 +/- 0.4%. There were a total of 672 transitions between modes of activity during a match. The results of this study suggest that refereeing top English rugby football union matches is physically demanding. Although the major physiological load is placed on the oxygen transport system, frequent sprint bouts and the associated requirements for acceleration and deceleration impose additional metabolic demands on referees. This information may be used in the design of physical training programmes to optimize performance in referees.

Adult↗
PubMed2001

Spread of a multiresistant strain of Pseudomonas aeruginosa in an adult cystic fibrosis clinic.

We initiated a prospective surveillance study to investigate possible Pseudomonas aeruginosa cross-infection in our cystic fibrosis centre. We characterised isolates by pyocin typing and pulsed-field gel electrophoresis. 22 (14%) of 154 patients with chronic P aeruginosa had isolates with similar and new pyocin and pulsed-field gel electrophoresis types. The shared isolates showed unusual phenotypic features: they were non-pigmented, non-motile, and resistant to a number of antipseudomonal antibiotics. Cross-infection by a multiresistant P aeruginosa strain has therefore occurred in patients attending our cystic fibrosis centre. We recommend microbiological surveillance in other cystic fibrosis centres.

Adult↗
PubMed2001

Modulation of cell proliferation by heterotrimeric G protein in Arabidopsis.

The alpha subunit of a prototypical heterotrimeric GTP-binding protein (G protein), which is encoded by a single gene (GPA1) in Arabidopsis, is a modulator of plant cell proliferation. gpa1 null mutants have reduced cell division in aerial tissues throughout development. Inducible overexpression of GPA1 in Arabidopsis confers inducible ectopic cell division. GPA1 overexpression in synchronized BY-2 cells causes premature advance of the nuclear cycle and the premature appearance of a division wall. Results from loss of function and ectopic expression and activation of GPA1 indicate that this subunit is a positive modulator of cell division in plants.

2,4-Dichlorophenoxyacetic Acid↗
PubMed2001

G protein regulation of ion channels and abscisic acid signaling in Arabidopsis guard cells.

The phytohormone abscisic acid (ABA) promotes plant water conservation by decreasing the apertures of stomatal pores in the epidermis through which water loss occurs. We found that Arabidopsis thaliana plants harboring transferred DNA insertional mutations in the sole prototypical heterotrimeric GTP-binding (G) protein alpha subunit gene, GPA1, lack both ABA inhibition of guard cell inward K(+) channels and pH-independent ABA activation of anion channels. Stomatal opening in gpa1 plants is insensitive to inhibition by ABA, and the rate of water loss from gpa1 mutants is greater than that from wild-type plants. Manipulation of G protein status in guard cells may provide a mechanism for controlling plant water balance.

Abscisic Acid↗
PubMed2001

ABP1 is required for organized cell elongation and division in Arabidopsis embryogenesis.

To directly address the function of a putative auxin receptor designated ABP1, a reverse genetic approach was taken to identify and characterize ABP1 mutant alleles in Arabidopsis. A homozygous null mutation in ABP1 confers embryo lethality. Null mutant embryos develop normally until the early stages of the globular embryo but are unable to make the transition to a bilaterally symmetrical structure because cells fail to elongate. Cell division was also aberrant both in the suspensor and embryo proper. Antisense suppression of ABP1 in tobacco cells causes slow proliferation and eliminates auxin-induced cell elongation and reduces cell division. The complete lack of auxin-inducible elongation in individual cells confirms the results observed in embryos, indicates a cell autonomous function, and, taken together with biochemical evidence that ABP1 binds auxins, suggests that ABP1 mediates auxin-induced cell elongation and, directly or indirectly, cell division.

Alleles↗
PubMed2001

Comparison of transcranial color Doppler imaging (TCDI) and transcranial Doppler (TCD) in children with sickle-cell anemia.

BACKGROUND: Transcranial Doppler (TCD) has been demonstrated to identify those at highest risk of stroke among children with sickle-cell disease. Based on a randomized clinical trial [Stroke Prevention in Sickle-Cell Anemia Trial (STOP)], which ended in 1997, the National Heart Lung and Blood Division of NIH has recommended TCD screening and chronic blood transfusion based on Nicolet TC 2000 dedicated Doppler (TCD). Studies performed using TCD imaging modalities need to be correlated to that used in the clinical trial to provide information for treatment decisions when screening with TCDI. OBJECTIVE: To correlate transcranial arterial time-averaged mean velocities obtained from an Acuson Transcranial Doppler Imaging to those obtained using the TCD as the gold standard for treatment decisions based on STOP. MATERIALS AND METHODS: A total of 29 children with sickle-cell disease, age 3-16 years, were studied at one of two scanning sessions using both techniques and a scanning protocol based on that used in STOP performed and read independently. The average difference in the measured velocities for each arterial segment was tested to determine difference from zero. Differences were compared before and after modifications to the TCDI technique were made to mimic the STOP protocol more closely. RESULTS: TCDI velocities were generally lower than TCD velocities for the same segment, but the difference was reduced (from 15 % to 10% for the middle cerebral artery) by modifications to the TCDI protocol. CONCLUSIONS: Measurements using the Acuson system are modestly lower than those obtained with dedicated Doppler using the Nicolet TCD.

Adolescent↗
PubMed2001

The relationship between critical velocity, maximal lactate steady-state velocity and lactate turnpoint velocity in runners.

In cycle exercise, it has been suggested that critical power, maximal lactate steady state, and lactate turnpoint all demarcate the transition between the heavy exercise domain (in which blood lactate is elevated above resting values but remains stable over time) and the very heavy exercise domain (in which blood lactate increases continuously throughout constant-intensity exercise). The purpose of the present study was to assess the level of agreement between critical velocity (CV), maximal lactate steady-state velocity (MLSSV), and lactate turnpoint velocity (LTPV) during treadmill running. Eight male subjects [mean (SD) age 28 (5) years, body mass 71.2 (8.0) kg, maximum oxygen uptake 54.9 (3.2) ml.kg(-1).min(-1)) performed an incremental treadmill test for the determination of LTPV (defined as a sudden and sustained increase in blood lactate concentration ([La]) at approximately equals 2.0-5.0 mM). The subjects returned to the laboratory on eight or nine occasions for the determination of CV and MLSSV. The CV was determined from four treadmill runs at velocities that were chosen to result in exhaustion within 2-12 min. The MLSSV was determined from four or five treadmill runs of up to 30 min duration and defined as the highest velocity at which blood [La] increased by no more than 1.0 mM after between 10 and 30 min of exercise. Analysis of variance revealed no significant differences between [mean (SD)] CV [14.4 (1.1) km.h(-1)], MLSSV [13.8 (1.1) km.h(-1)] and LTPV [13.7 (0.6) km.h(-1)]. However, the bias +/-95% limits of agreement for comparisons between CV and MLSSV [0.6 (2.2) km.h(-1)], CV and LTPV [0.7 (2.7) km.h(-1)], and MLSSV and LTPV [0.1 (1.8) km.h(-1)] suggest that the extent of disagreement is too great to allow one variable to be estimated accurately from another in individual subjects. Direct determination of MLSSV is necessary if precision is required in experimental studies.

Adult↗
PubMed2001

Purification and characterisation of a non-plant myrosinase from the cabbage aphid Brevicoryne brassicae (L.).

Plant myrosinases and glucosinolates constitute a defence system in cruciferous plants towards pests and diseases. We have purified for the first time a non-plant myrosinase from the cabbage aphid Brevicoryne brassicae (L.) to homogeneity. The protein was N-terminally blocked and protease (trypsin and lys c) degradation gave peptides of which five were sequenced. The protein is a dimer with subunits of mass 54 kDa+/-500 Da. Western blot analysis with an anti-aphid myrosinase antibody showed a strong cross reaction with a protein extract from the Brassica specialist, B. brassicae. The anti-aphid myrosinase antibody does not cross react with plant myrosinase neither does an anti-plant myrosinase antibody cross react with aphid myrosinase.

Animals↗
PubMed2001

X-linked lymphoproliferative disease: three atypical cases.

Common variable immunodeficiency (CVID) is the most frequently occurring primary immunodeficiency in both children and adults. The molecular basis of CVID has not been defined, and diagnosis involves exclusion of other molecularly defined disorders. X-linked lymphoproliferative disease (XLP) is a rare disorder in which severe immunodysregulatory phenomena typically follow Epstein-Barr virus (EBV) infection. Boys who survive initial EBV infection have a high incidence of severe complications, including progressive immunodeficiency, aplastic anaemia, lymphoproliferative disease and lymphoma. Survival beyond the second decade is unusual, although bone marrow transplantation can be curative. Until recently reliable diagnostic testing for XLP has not been available, but the identification of the XLP gene, known as SH2D1A, and coding for a protein known as SAP, means that molecular diagnosis is now possible, both by protein expression assays, and mutation detection, although the mutation detection rate in several series is only 55-60%. We describe three male patients initially diagnosed as affected by CVID, one of whom developed fatal complications suggestive of XLP, and all of whom lack expression of SAP. Two out of three have disease-causing mutations in the SAP gene, consistent with published data for XLP. These findings raise the possibility that a subgroup of patients with CVID may be phenotypic variants of XLP. Further studies are necessary to investigate this possibility, and also to clarify the prognostic significance of SAP abnormalities in such patients in the absence of typical features of XLP.

Adolescent↗
PubMed2001

Increased levels of insulin-like growth factor binding protein-2 in sera and tumours from patients with colonic neoplasia with and without acromegaly.

OBJECTIVE: Patients with acromegaly are at increased risk of developing colorectal carcinoma and premalignant tubulovillous adenoma. The pathogenesis of these neoplasms could involve a stimulatory effect of serum growth factors on colonic epithelial cell proliferation. The aim of this study was to evaluate changes in (1) serum IGF-I, IGF-II, IGFBP-3 and IGFBP-2 and (2) changes in local expression of IGFBPs and p53 in colonic epithelium in patients with colonic neoplasia with and without acromegaly. DESIGN: A cross-sectional retrospective study was performed. Fasting serum samples were obtained at the time of colonoscopy for patients with acromegaly and at the time of surgery for patients with colonic neoplasia without acromegaly. MEASUREMENTS: Serum IGF-I, IGF-II, IGFBP-2 and IGFBP-3 were measured using specific immunoassays. Tissue expression of IGFBP-2, IGFBP-3 and p53 status were determined by immunohistochemistry. PATIENTS: Group 1: 26 age- and sex-matched control subjects (range 40-69 years); group 2: 18 patients with acromegaly without colonic neoplasia (range 39-68 years); group 3: 18 patients with acromegaly and colonic neoplasia (range 41-74 years, 11 = adenoma, seven = carcinoma); group 4: 19 patients with colonic neoplasia without endocrine disease (range 43-91 years, four = adenoma, 15 = carcinoma). Immunohistochemical staining of colonic biopsies was performed for IGFBP-2, IGFBP-3 and p53 in groups 3 and 4. RESULTS: Mean serum IGF-I and IGFBP-3 levels were significantly elevated in group 2 (371 +/- 131 microg/l and 6.5 +/- 1.8 mg/l, respectively) and group 3 (379 +/- 174 microg/l and 5.8 +/- 1.6 mg/l, respectively), and significantly reduced in group 4 (103 +/- 36 microg/l and 2.4 +/- 1 mg/l) compared to controls (165 +/- 40 microg/l and 4.7 +/- 1 mg/l; P < 0.0001, P < 0.001, respectively). However, median serum IGFBP-2 levels were significantly elevated in group 3 (P < 0.01) and group 4 (P < 0.0001). Immunostaining for IGFBP-2 showed strong areas of immunoreactivity in the cytoplasm of malignant colonic epithelium compared to benign epithelium. IGFBP-3 immunostaining showed strong areas of immunoreactivity in the cytoplasm and in the nucleus of malignant and benign colonic epithelium compared to the normal epithelium. Nuclear staining for p53 was observed in three patients from group 3 (two carcinoma, one adenoma) and four patients from group 4 (all carcinoma). CONCLUSION: Our results describe changes in IGFBP-2 expression in colonic neoplasia in patients with and without acromegaly, which suggest that this binding protein may regulate local bioavailability of IGF, which in turn could modulate colonic cell proliferation and/or differentiation.

Acromegaly↗