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Biomedical subjects

D A Jones

Publications and source records attributed to D A Jones.

At least 37 records · Page 2Linked to original sources

The contribution of transfusion to HCV infection in England.

The English HCV lookback programme has identified some individuals with transfusion-transmitted HCV infection. The path from the collection of donations from HCV-infected donors to the identification of infected recipients was constructed. The probability of different outcomes at each branch was derived from data collected during this programme. This path of probabilities was then used to produce a complete estimate of the number of recipients infected by blood transfusions (dead and alive at the end of 1995) by re-entry of blood components that fell out of the lookback at various steps prior to recipient testing, and entry of components from HCV-infected donations that were never identified for lookback. Less than 14,000 recipients were estimated to have been infected with HCV during the decade prior to the start of donation testing. Over 60% of these were expected to have died by the end of 1995. Transfusion has infected a large group of individuals. However, this group constitutes a very small, and declining, proportion of all HCV infections in the population.

Blood Transfusion↗

Effects of inspiratory muscle training upon recovery time during high intensity, repetitive sprint activity.

The present study examined the influence of specific inspiratory muscle training (IMT) upon recovery time during repetitive sprint activity, as well as the physiological and perceptual responses to fixed intensity shuttle running. Using a double-blind placebo-controlled design, 24 male repetitive sprint athletes were assigned randomly to either an IMT (n = 12) or placebo (n = 12) group. The self-selected recovery time during a repetitive sprint test and the physiological response to submaximal endurance exercise were determined. Following completion of baseline and pre-intervention measures, the IMT group performed 30 inspiratory efforts twice daily against a resistance equivalent to 50 % maximum inspiratory mouth pressure (MIP) for 6 wk. The placebo group performed 60 breaths once daily, for 6 wk, at a resistance equivalent to 15 % MIP, a load known to elicit negligible changes in respiratory muscle function. The IMT group improved total recovery time during the repetitive sprint test by 6.2 +/- 1.1 % (mean +/- SEM) above the changes noted for the placebo group (p = 0.006). Blood lactate and perceptual responses to submaximal exercise were also significantly attenuated following IMT (p </= 0.01). These data support existing evidence that specific IMT attenuates the blood lactate and perceptual responses to submaximal endurance exercise. In addition, the present study provides new evidence that IMT improves recovery time during high intensity, intermittent exercise in repetitive sprint athletes.

Adult↗

Developmental control of promoter activity is not responsible for mature onset of Cf-9B-mediated resistance to leaf mold in tomato.

Cf-9 confers resistance to tomato seedlings and mature plants against Cladosporium fulvum races expressing the Avr9 elicitor. It is the central member of a cluster of five paralogous genes in an introgressed segment of chromosome 1 derived from Lycopersicon pimpinellifolium. The other four genes have been named Hcr9-9A, Hcr9-9B, Hcr9-9D, and Hcr9-9E. Hcr9-9B, here designated Cf-9B, encodes weaker resistance than Cf-9, recognizes a different elicitor, and protects only mature plants from infection. The onset of Cf-9B-mediated resistance and the molecular basis for its developmental control were investigated in this study. Fungal inoculation of tomato plants containing reciprocal Cf-9/Cf-9B promoter-coding region swaps, analysis of tomato plants containing promoter-gusA fusions, and a reverse transcriptase-polymerase chain reaction study of Cf-9 and Cf-9B transcripts in tomato plants suggested that transcriptional control of Cf-9B did not account for the late onset of Cf-9B-mediated resistance. Alternative explanations for the onset of Cf-9B-mediated resistance in mature plants are discussed.

Base Sequence↗

Fatigue is not a necessary stimulus for strength gains during resistance training.

BACKGROUND: High resistance training enhances muscular strength, and recent work has suggested an important role for metabolite accumulation in this process. OBJECTIVE: To investigate the role of fatigue and metabolite accumulation in strength gains by comparing highly fatiguing and non-fatiguing isotonic training protocols. METHODS: Twenty three healthy adults (18-29 years of age; eight women) were assigned to either a high fatigue protocol (HF: four sets of 10 repetitions with 30 seconds rest between sets) to maximise metabolic stress or a low fatigue protocol (LF: 40 repetitions with 30 seconds between each repetition) to minimise changes. Subjects lifted on average 73% of their 1 repetition maximum through the full range of knee extension with both legs, three times a week. Quadriceps isometric strength of each leg was measured at a knee joint angle of 1.57 rad (90 degrees ), and a Cybex 340 isokinetic dynamometer was used to measure the angle-torque and torque-velocity relations of the non-dominant leg. RESULTS: At the mid-point of the training, the HF group had 50% greater gains in isometric strength, although this was not significant (4.5 weeks: HF, 13.3 (4.4)%; LF, 8.9 (3.6)%). This rate of increase was not sustained by the HF group, and after nine weeks of training all the strength measurements showed similar improvements for both groups (isometric strength: HF, 18.2 (3.9)%; LF, 14.5 (4.0)%). The strength gains were limited to the longer muscle lengths despite training over the full range of movement. CONCLUSIONS: Fatigue and metabolite accumulation do not appear to be critical stimuli for strength gain, and resistance training can be effective without the severe discomfort and acute physical effort associated with fatiguing contractions.

Adult↗

Dolichol-phosphate-mannose-3 (DPM3)/prostin-1 is a novel phospholipase C-gamma regulated gene negatively associated with prostate tumor invasion.

The most ominous development in tumor progression is the transition to an invasive and metastatic phenotype. Little is known, however, about the molecular alterations that cause a tumor to become invasive. In view of this, we have used microarray expression analysis to evaluate the expression profiles of a unique panel of human DU145 prostate cancer sublines that vary in their invasive potential. The three DU145 sublines expressed epidermal growth factor (EGF) receptors that differed in their ability to activate phospholipase C-gamma (PLC gamma). Three-way analyses yielded 11 genes out of 4608 genes screened that associated directly or inversely with invasive potential. The gene whose expression correlated most strongly with lack of invasion was identified as a potential invasion suppressor and called prostin-1. Pharmacological inhibition of PLC gamma (U73122) confirmed that PLC gamma signaling suppressed prostin-1 in that U73122 treatment caused induction of prostin-1 in PLC gamma competent cells. The prostin-1 gene, conserved through phylogeny, is induced by androgen in LNCaP cells and encodes a 92 amino acid protein. The protein shares no extensive homologies with other known genes, yet was recently identified as a small stabilizer subunit of the dolichol-phosphate-mannose (DPM) synthase complex. That DPM3/prostin-1 might suppress tumor progression was supported by the finding that exogenous expression in COS cells leads to apoptosis. These findings support the use of model cell lines to identify putative tumor suppressors and promoters.

Base Sequence↗

Assessment of tumor necrosis factor receptor and Fas signaling pathways by transcriptional profiling.

Apoptosis, or programmed cell death, is an important mechanism by which cells are eliminated during immune regulation and embryonic development. Aberrations in the signaling pathways leading to apoptosis may result in cancer, autoimmune diseases, or inflammatory disorders. In view of this, an understanding of the signaling capabilities of apoptosis-inducing or death receptors is essential to understanding their roles in biology and disease. We used cDNA microarrays to examine the downstream transcriptional effects of two members of the tumor necrosis factor (TNF) family of death receptor ligands. We compared the transcriptional responses of a model colon cancer cell line, HT29, to TNF-alpha and anti-Fas activating antibody. Both ligands induced a subset of genes characteristic of activation of the transcription factor nuclear factor-kappaB (NF-kappaB). Follow-up analyses demonstrated that, although TNF-alpha activated NF-kappaB through IkappaB-alpha degradation, alpha-Fas treatment led to NF-kappaB activation through a mechanism distinct from IkappaB-alpha degradation.

Antibodies, Monoclonal↗

Quantifying the 5-HT1A agonist action of buspirone in man.

RATIONALE: Buspirone is used as a neuroendocrine challenge in which the increase of circulating prolactin is taken as a measure of the sensitivity of central serotonergic (5-HT(1A)) pathways. Interpretation of the test is complicated, however, by the fact that buspirone possesses D(2) antagonist and 5-HT(1A) agonist activity, both of which will result in the release of prolactin. To understand the significance of prolactin secretion in response to buspirone, it is important to measure the differential actions of the two controlling pathways. OBJECTIVE: To characterise the dual action of buspirone in stimulating the secretion of prolactin by blocking the 5-HT(1A) action with the 5-HT1A antagonist action of pindolol. METHODS: Healthy male subjects (n=35) received buspirone (0.5 mg x kg bw(-1) orally) with and without pre-treatment with the 5-HT(1A) receptor antagonist pindolol (40 mg over 2 days, 0.5 mg x kg bw(-1) on test day). Nine subjects underwent two additional trials in which they received a placebo with and without pre-treatment with pindolol. RESULTS: Pindolol alone caused a small but significant reduction (18%) in the tonic release of prolactin. Buspirone alone produced a robust prolactin response which was reduced to approximately half by pindolol pre-treatment. Pindolol pre-treatment also, on average, delayed the onset and peak of the prolactin response. There was wide variation among individuals both in the absolute response to buspirone and in the proportion that could be attributed to the non-serotonergic agonist action of buspirone (22-82% IQ range). CONCLUSIONS: Our results indicate that while serotonergic pathways play a minor role in the tonic release of prolactin, the response to a buspirone challenge alone cannot be used as a simple index of central serotonergic activity. However, if two challenges are carried out, one with buspirone and the other with buspirone plus pindolol, quantitative measures can be made of the sensitivity of both the 5-HT(1A) and the putative D(2) pathways controlling prolactin release.

Adolescent↗

Digestion in relation to feeding strategies exhibited by crustacean larvae.

Decapod crustaceans have adopted a full range of reproductive strategies from the release of large numbers of small eggs (Penaeoidea) to the release of relatively low numbers of large advanced larvae (Nephropidae). As larval size determines trophic position in planktonic food webs, all food sources from phyto- to zooplankton are exploited, with many species changing trophic level during ontogenetic development. Comparative studies on digestive enzymes, levels of activity and changes during ontogeny, together with measurements of gastroevacuation rates and food energy values appear to reveal a general pattern. While herbivorous decapod larvae adapt to low food energy values with high enzyme activity levels, rapid food turnover and low assimilation efficiency, carnivorous larvae exhibit low levels of enzyme activity but compensate by extending retention time of high-energy food to maximise assimilation efficiency. New studies on digestive enzyme levels during development in the penaeid Litopenaeus vannamei, the caridean Lysmata debelius and the cirriped Elminius modestus, appear to agree with previous observations.

Animals↗

The pathophysiology of the intervertebral disc.

After a review of disk structure, the pivotal role of disk cells in producing and renewing the extracellular disk matrix is emphasized. Disk cells rely on nutrients that diffuse through the vertebral endplates. Microelectrode methods have been developed to study nutrient diffusion and endplate permeability. Mechanical stimuli modify disk cell activity. Scoliosis is associated with decreased endplate permeability, a factor that may play a role in disk degeneration and scoliosis progression.

Back Pain↗

Non-inflammatory corneal complications of contact lens wear.

Contact lenses can induce changes in the epithelium, stroma and endothelium of the cornea, all of which can be observed clinically using the slit-lamp biomicroscope. These complications include epithelial microcysts, vacuoles and staining, stromal oedema and vascularization, and endothelial polymegethism and blebs. Each complication can be attributed to one or more aetiological factors such as hypoxia, hypercapnia, tissue acidosis, trauma, hypersensitivity and toxicity. This review outlines the way in which these complications manifest clinically, and consideration is given to management strategies and likely prognoses. Early detection of these conditions and appropriate action can usually prevent more serious ocular complications.

Journal Article↗

Preservation of RNA for functional genomic studies: a multidisciplinary tumor bank protocol.

Few human tumors are collected such that RNA is preserved for molecular analysis. Completion of the Human Genome Project will soon result in the identification of more than 100,000 new genes. Consequently, increasing attention is being diverted to identifying the function of these newly described genes. Here we describe a multidisciplinary tumor bank procurement protocol that preserves both the integrity of tissue for pathologic diagnosis, and the RNA for molecular analyses. Freshly excised normal skin was obtained from five patients undergoing wound reconstruction following Mohs micrographic surgery for cutaneous neoplasia. Tissues treated for 24 hours with RNAlater were compared histologically and immunohistochemically to tissues not treated with RNAlater. Immunohistochemical stains studied included: CD45, CEA, cytokeratin AE1/3, vimentin, S-100, and CD34 on formalin-fixed, paraffin embedded tissue and CD45 staining of frozen tissue. Slides were blinded and evaluated independently by three pathologists. The histologic and immunohistochemical parameters of tissue stored in RNAlater were indistinguishable from tissue processed in standard fashion with the exception of S-100 stain which failed to identify melanocytes or Langerhan's cells within the epidermis in any of the RNAlater-treated tissues. Interestingly, nerve trunks within the dermis stained appropriately for S-100. Multiple non-cutaneous autopsy tissues were treated with RNAlater, formalin, liquid nitrogen (LN2), and TRIzol Reagent. The pathologists were unable to distinguish between tissues treated with RNAlater, formalin, or frozen in LN2, but could easily distinguish tissues treated with TRIzol Reagent because of extensive cytolysis. RNA was isolated from a portion of the tissue treated with RNAlater and used for molecular studies including Northern blotting and microarray analysis. RNA was adequate for Northern blot analysis and mRNA purified from RNAlater-treated tissues consistently provided excellent templates for reverse transcription and subsequent microarray analysis. We conclude that tissues treated with RNAlater before routine processing are indistinguishable histologically and immunohistochemically from tissues processed in routine fashion and that the RNA isolated from these tissues is of high quality and can be used for molecular studies. Based on this study, we developed a multidisciplinary tumor bank procurement protocol in which fresh tissue from resection specimens are routinely stored in RNAlater at the time of preliminary dissection. Thus, precious human tissue can be utilized for functional genomic studies without compromising the tissue's diagnostic and prognostic qualities.

Aged↗

The relationship between pedometer-determined ambulatory activity and body composition variables.

OBJECTIVE: To examine the relationship between pedometer-determined ambulatory activity (steps/day) and body composition variables body mass index (BMI) and percentage body fat). DESIGN: : Secondary analysis of a cross-sectional objective activity monitoring study for up to 21 consecutive days. SUBJECTS: A total of 109 apparently healthy adults (eight African American males, 23 African-American females, 33 Caucasian males, 45 Caucasian females), age 44.9+/-15.8 y, BMI=26.9+/-5.1 kg/m2. MEASUREMENTS: Pedometer-assessed ambulatory activity (steps/day), height and weight, and percentage body fat by bioelectrical impedance. RESULTS: Analyzed as both a continuous and a categorical variable (determined using 25th and 75th percentiles for distribution for steps/day), ambulatory activity was consistently related to body composition variables. Steps/day was inversely correlated with BMI and percentage body fat (r=-0.30, and r=-0.27, respectively, both P<0.01). The consistency of the relationship was also evident when examined using accepted BMI cut-off points for normal-weight, overweight, and obese categories. CONCLUSIONS: Individuals in this small sample with values greater than approximately 9000 steps/day are more frequently classified as normal weight for height. Individuals with values less than approximately 5000 steps/day are more frequently classified as obese. These findings require further corroborative investigation but provide preliminary cutoff points for identifying individuals at risk who may benefit from appropriate physical activity intervention.

Adolescent↗

Outcome following surgical closure of secundum atrial septal defect.

OBJECTIVE: To assess the current outcome of surgical closure of secundum atrial septal defects (ASD) in an Australian paediatric population. METHODOLOGY: A retrospective chart review of 87 children, aged 2 months to 15 years, was performed for surgery between August 1995 and March 1999. RESULTS: There were no deaths in the patients studied. Approximately one in four patients (24.1%) experienced complications requiring further management. Complication rates were similar to those published previously. However, one in nine patients (11.5%) required surgical drainage of a pericardial effusion. A total of five of 87 (5.7%) patients developed post-pericardiotomy syndrome (PPS), of whom four required pericardiocentesis. The risk for developing a pericardial effusion requiring drainage or PPS was more than twice in children older than 5 years of age at the time of surgery compared to those aged under 5 years, although there was an insufficient number of subjects in the study to prove this statistically (Odds ratio 2.31). CONCLUSIONS: Most patients have an uncomplicated postoperative course following surgical closure of secundum ASD. However, a significant minority (24.1%) do develop complications requiring further management and have a correspondingly longer period of hospitalization. Patients older than 5 years of age were identified as being potentially at greater risk for the development of PPS or a pericardial effusion requiring drainage. Further research needs to be performed to clarify this.

Adolescent↗

Glycopeptide prescribing in an Australian tertiary paediatric hospital.

OBJECTIVE: To assess the extent and appropriateness of glycopeptide use in a tertiary Australian Paediatric hospital. METHODOLOGY: A retrospective analysis of prescriptions during a six-month period between July 1999 and January 2000. Medical records were examined and prescribing practices compared with the recommendations of the Hospital Infectious Control Practices Advisory Committee (HICPAC) and the Infectious Diseases Society of America (IDSA). RESULTS: Fifty-one patients were identified who received a total of 98 glycopeptide prescriptions. The Haematology/ Oncology unit prescribed 71/98 (72.4%). 68/98 (69.4%) patients received vancomycin, 9/98 (9.2%) received teicoplanin and 21/98 (21.4%) a combination of both. 81/98 (82.7%) had central venous catheters and 69/98 (70.4%) were immunocompromised. 48/98 (49%) prescriptions were for empiric treatment with 38/98 (38.8%) for prophylaxis and 11/98 (12.2%) therapeutic. 19/98 (19.4%) prescriptions were deemed appropriate, 6 (6.1%) by HICPAC criteria, and a further 13 (13.3%) by IDSA or other criteria. Of 19 prescriptions started appropriately, only 7/17 (41.1%) were continued appropriately beyond 48 h. Appropriate cultures were taken before prescription in 93.3% of cases. Dose was appropriate in 91/98 (92.9%) and frequency appropriate in all cases. The cost of inappropriate prescribing was approximately $9500. DISCUSSION: A high rate of inappropriate glycopeptide prescribing was evident in this paediatric population. Inappropriate prescribing existed across all subspecialties. Use was primarily for empiric therapy and prophylaxis in young children with an oncology diagnosis. A number of situations existed where glycopeptide prescription was felt appropriate despite not being included in HICPAC/IDSA guidelines. Areas with high rates of inappropriate prescribing were identified and will be targeted for education and intervention. Audit of practice continues.

Adolescent↗

Anxiety in patients having caesarean section under regional anaesthesia: a questionnaire and pilot study.

The aim of this pilot study was to investigate anxiety levels in patients undergoing elective caesarean section under regional anaesthesia, and to ascertain whether this group of patients considered the administration of anxiolytic premedicant drugs before surgery acceptable. Anxiety was assessed by two means, using a self-reported anxiety score and a physiological evaluation in the form of skin conductance measurements. The patient was given an information sheet explaining the potential advantages and disadvantages associated with the use of temazepam as an anxiolytic premedicant before caesarean section. Having read the information sheet, the patient's opinion regarding the use of anxiolytic premedicant drugs in this context was determined using a questionnaire. Most women reported high preoperative anxiety levels, although the cause of their anxiety was not determined. In our hospital, a significant proportion of such women would accept temazepam as anxiolytic premedication, despite being aware of its potential adverse side effects.

Journal Article↗

The use of neostigmine to treat postoperative ileus in orthopedic spinal patients.

Ileus is a common complication of spinal surgery, affecting 5% to 12% of all patients. Often this ileus is secondary to acute colonic pseudo-obstruction. This study is a prospective clinical trial of neostigmine in seven spinal patients with ileus after surgery to demonstrate its efficacy. All patients had evidence of the Ogilvie syndrome that was unresponsive to 24 hours of conservative therapy. Patients received 2 mg neostigmine, and abdominal circumference, clinical response, and radiographic colonic measurements were recorded. Patients were followed for recurrence of ileus for their remaining time in the hospital. Six patients had prompt colonic decompression, and no patient had recurrence of colonic distension. Side effects were minimal. These results suggest that postoperative spinal patients with ileus secondary to acute colonic pseudo-obstruction that is unresponsive to conservative therapy benefit from treatment with neostigmine, resulting in safe, rapid decompression of the colon.

Adolescent↗