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Biomedical subjects

J Fletcher

Publications and source records attributed to J Fletcher.

At least 19 recordsLinked to original sources

The multidisciplinary team meeting improves staging accuracy and treatment selection for gastro-esophageal cancer.

The object of this article is to assess current staging accuracies for individual modalities and to investigate the influence of the multidisciplinary team (MDT) on clinical staging accuracies and treatment selection for patients with gastro-esophageal cancer. Patients newly diagnosed with gastric or esophageal cancer and who were deemed suitable for surgical resection by the MDT were studied. Patients were staged with a combination of computerized tomography (CT), endoscopic ultrasound (EUS) and laparoscopic ultrasound (LUS). Additionally, the MDT determined an overall clinical stage for each patient after discussion at the MDT meeting. Treatments were selected according to this final clinical stage. Final histopathological staging (pTNM) was available for all patients and was used as the gold standard for determining staging accuracy. Suitability of treatment selection was assessed once final pTNM was available. One hundred and eighteen patients were studied. Endoscopic ultrasound was the most accurate individual staging modality for the loco-regional assessment of esophageal tumors (T stage accuracy 78%, N stage accuracy 70%). Laparoscopic ultrasound was the most accurate modality in T staging of gastric cancers (91%). The MDT stage was more accurate than each individual staging modality for T and N staging for both gastric and esophageal cancers (accuracy range: 88-89%) and was better for the assessment of nodal disease than each individual modality (CT P < 0.001, EUS P < 0.01, LUS P < 0.01). Overall staging accuracy as determined at the MDT meeting was increased and resulted in only 2/118 (2%) patients being under-treated. The MDT significantly improves staging accuracy for gastro-esophageal cancer and ensures that correct management decisions are made for the highest number of individual patients.

Adenocarcinoma↗

Plant pathogen forensics: capabilities, needs, and recommendations.

A biological attack on U.S. crops, rangelands, or forests could reduce yield and quality, erode consumer confidence, affect economic health and the environment, and possibly impact human nutrition and international relations. Preparedness for a crop bioterror event requires a strong national security plan that includes steps for microbial forensics and criminal attribution. However, U.S. crop producers, consultants, and agricultural scientists have traditionally focused primarily on strategies for prevention and management of diseases introduced naturally or unintentionally rather than on responding appropriately to an intentional pathogen introduction. We assess currently available information, technologies, and resources that were developed originally to ensure plant health but also could be utilized for postintroduction plant pathogen forensics. Recommendations for prioritization of efforts and resource expenditures needed to enhance our plant pathogen forensics capabilities are presented.

Bioterrorism↗

The influence of small fibre muscle mechanoreceptors on the cardiac vagus in humans.

We have previously shown that activation of muscle receptors by passive stretch (PS) increases heart rate (HR) with little change in blood pressure (BP). We proposed that PS selectively inhibits cardiac vagal activity. We attempted to test this by performing PS during experimental alterations in vagal tone. Large decreases in vagal tone were induced using either glycopyrrolate or mild rhythmic exercise. Milder alterations in vagal tone were achieved by altering carotid baroreceptor input: neck pressure (NP) or neck suction (NS). PS of the triceps surae was tested in 14 healthy human volunteers. BP, ECG and respiration were recorded. PS alone caused a significant decrease (P < 0.05) in R-R interval (962 +/- 76 ms at baseline compared to 846 +/- 151 ms with PS), and showed a reduction in HR variability, which was not significant. The decrease in R-R interval with PS was significantly less (P < 0.05, n = 3) following administration of glycopyrrolate (-8.1 +/- 4.5 ms) compared to PS alone (-54 +/- 11 ms), and also with PS during handgrip (+10 +/- 10 ms) compared with PS alone (-74 +/- 15 ms) (P < 0.05, n = 5). Milder reductions in vagal activity (NP) resulted in a small but insignificant further decrease in R-R interval in response to PS (-107 +/- 17 ms compared to PS alone -96 +/- 13 ms, n = 5). Mild increases in vagal activity (NS) during PS resulted in smaller decreases in R-R interval (-39 +/- 5.5 ms) compared to PS alone (-86 +/- 17 ms) (P < 0.05, n = 8). BP was not significantly changed by stretch in any tests. The results indicate that amongst muscle receptors there is a specific group activated by stretch that selectively inhibit cardiac vagal tone to produce tachycardia.

Adult↗

Cardiac vagal tone, exercise performance and the effect of respiratory training.

Heart rate variability (HRV) at rest and heart rate recovery after exercise reflect cardiac vagal activity. The aim of this study was to determine whether increasing HRV during involuntary respiratory training induced by rebreathing air using a Hepburn heart and lung exerciser (HHALE) could, like exercise, improve vagal tone. Eighteen subjects (36-88 years) underwent a 6-week control period, then a 6-week training period with the HHALE following which half continued training for 6 weeks and half ceased training. Measurements were made of HRV, work at 60% predicted heart rate max for 15 min, heart rate recovery after exercise, resting blood pressure, heart rate, vital capacity and forced expiratory volume. After the first 6-week HHALE training, there was a significant increase of 13.2 +/- 5.7 nu in the high frequency peak of the power spectrum of HRV at rest, whereas, the low frequency peak decreased. Similarly, exercise performance showed a significant improvement of 0.031 +/- 0.012 J per heartbeat from a pre-training 0.128 +/- 0.022. Also, heart rate recovery after exercise significantly faster (drop in the first 20 s improving by 3.3 +/- 1.5 beats from a pre-training 12.9 +/- 1.6). The subgroup that continued training maintained or slightly improved these values. In those that ceased training the speed of heart rate recovery at the end of the exercise test returned to pre-trained levels, whereas, other responses were either maintained or decreased slightly. We conclude that training with the HHALE can, without additional exercise, increase cardiac vagal tone and exercise performance.

Adaptation, Physiological↗

Exsheathment of Ostertagia ostertagi infective larvae following exposure to bovine rumen contents derived from low and high roughage diets.

The objective of this study was to characterize the exsheathment kinetics of Ostertagia ostertagi infective larvae (L3) following in vivo exposure to bovine rumen contents derived from low and high roughage diets. O. ostertagi L3 were placed in disposable dialysis bags and incubated for various time points between 0 and 360 min in the rumen of a fistulated steer maintained on a 71% grain diet or a 100% grass diet. The maximum percentage of exsheathed L3 was observed 120 min post-exposure to grass-derived rumen contents, while maximum exsheathment for L3 exposed to grain-derived rumen contents did not occur until 360 min. This work provides the first report of the in vivo exsheathment kinetics for O. ostertagi in its bovine host. Results of this study also support earlier reports that rumen pH may affect the exsheathment efficiency of abomasal trichostrongylids.

Animals↗

Genomic comparison of plant pathogenic and nonpathogenic Serratia marcescens strains by suppressive subtractive hybridization.

Cucurbit yellow vine disease (CYVD) is caused by disease-associated Serratia marcescens strains that have phenotypes significantly different from those of nonphytopathogenic strains. To identify the genetic differences responsible for pathogenicity-related phenotypes, we used a suppressive subtractive hybridization (SSH) strategy. S. marcescens strain Z01-A, isolated from CYVD-affected zucchini, was used as the tester, whereas rice endophytic S. marcescens strain R02-A (IRBG 502) was used as the driver. SSH revealed 48 sequences, ranging from 200 to 700 bp, that were present in Z01-A but absent in R02-A. Sequence analysis showed that a large proportion of these sequences resembled genes involved in synthesis of surface structures. By construction of a fosmid library, followed by colony hybridization, selection, and DNA sequencing, a phage gene cluster and a genome island containing a fimbrial-gene cluster were identified. Arrayed dot hybridization showed that the conservation of subtracted sequences among CYVD pathogenic and nonpathogenic S. marcescens strains varied. Thirty-four sequences were present only in pathogenic strains. Primers were designed based on one Z01-A-specific sequence, A79, and used in a multiplex PCR to discriminate between S. marcescens strains causing CYVD and those from other ecological niches.

Base Sequence↗

Studies of acid exposure immediately above the gastro-oesophageal squamocolumnar junction: evidence of short segment reflux.

BACKGROUND AND AIMS: Oesophageal pH is conventionally recorded from a point 5 cm above the lower oesophageal sphincter. However, the mucosal changes of reflux oesophagitis and intestinal metaplasia tend to affect the segment of oesophagus distal to this and close to the squamocolumnar junction. This study set out to investigate oesophageal acid exposure of squamous mucosa close to the squamocolumnar junction. METHODS: Dual channel 24 hour pH monitoring was carried out in 11 patients with endoscopy negative dyspepsia and no evidence of gastro-oesophageal reflux by conventional oesophageal pH metry. Oesophageal pH was recorded from electrodes positioned 5 mm and 55 mm proximal to the squamocolumnar junction. A novel technique was developed using metal clips to secure the pH catheter to the oesophageal mucosa and maintain these electrode positions. Oesophageal manometry indicated that the distal electrode was within the high pressure zone of the lower oesophageal sphincter. RESULTS: We found that 24 hour oesophageal acid exposure (per cent time pH <4) was greater 5 mm above the squamocolumnar junction compared with the conventional position 5 cm more proximal (11.7% v 1.8%; p<0.001). The greater acid exposure at the distal versus the conventional site was apparent in both the upright (12.7% v 2.3%) and supine (10.5% v 1.3%) positions, as well as during preprandial (14.2% v 1.6%) and postprandial (21.8% v 2.8%) periods (p<0.001 for each). The number of reflux events recorded close to the squamocolumnar junction was also higher than at the conventional position (168 v 33; p<0.001). There was no correlation between acid exposure at the two sites. CONCLUSIONS: The squamous mucosa of the most distal oesophagus is exposed to substantial acidic reflux, even in patients without evidence of conventional reflux disease. This short segment reflux may explain the high incidence of metaplasia and neoplasia at the gastro-oesophageal junction.

Adult↗

Overwintering squash bugs harbor and transmit the causal agent of cucurbit yellow vine disease.

Since 1988, cucurbit crops, particularly watermelon, cantaloupe, and squash, grown in Oklahoma and Texas have experienced devastating losses from cucurbit yellow vine disease (CYVD), caused by the phloem-limited bacterium Serratia marcescens Bizio. Squash bug, Anasa tristis (De Geer), is a putative vector of the pathogen. In 2000-2001, overwintering populations of squash bug collected from DeLeon, TX, were tested for their ability to harbor and transmit the bacterium. Individual squash bugs (n = 73) were caged serially for periods of up to 7 d on at least four squash seedlings. Two studies were conducted, one with insects collected in November 2000 placed on first true leaf-stage seedlings and the second with insects from an April 2001 collection, placed on 3-5 true leaf-stage squash. Controls consisted of squash seedlings caged without insects. Squash bug transmission rates of the pathogen in studies I and II were 20 and 7.5%, respectively. Overall, 11.0% of the squash bugs harbored and successfully transmitted the bacterium to squash seedlings. All control plants tested negative for S. marcescens and did not exhibit CYVD. Female squash bugs killed a significantly greater proportion of young first leaf-stage seedlings than males. Feeding on 3-5 leaf-stage squash resulted in no plant mortality regardless of squash bug gender. This study demonstrated that the squash bug harbors S. marcescens in its overwintering state. The squash bug-S. marcescens overwintering relationship reported herein greatly elevates the pest status of squash bug and places more importance on development of integrated strategies for reducing potential overwintering and emerging squash bug populations.

Animals↗

Gene content and organization of an 85-kb DNA segment from the genome of the phytopathogenic mollicute Spiroplasma kunkelii.

Spiroplasma kunkelii, the causative agent of corn stunt disease in maize (Zea maysL.), is a helical, cell wall-less prokaryote assigned to the class Mollicutes. As part of a project to sequence the entire S. kunkelii genome, we analyzed an 85-kb DNA segment from the pathogenic strain CR2-3x. This genome segment contains 101 ORFs and two tRNA genes. The majority of the ORFs code for predicted proteins that can be assigned to respective clusters of orthologous groups (COGs). These COGs cover diverse functional categories including genetic information storage and processing, cellular processes, and metabolism. The most notable gene cluster in this genome segment is a super-operon capable of encoding 24 ribosomal proteins. The organization of genes in this operon reflects the unique evolutionary position of the spiroplasma. Gene duplications, domain rearrangements, and frameshift mutations in the segment are interpreted as indicators of phase variation in the spiroplasma. To our knowledge, this is the first analysis of a large genome segment from a plant pathogenic spiroplasma.

Base Sequence↗

Report from the Faculty of Family Planning and Reproductive Health Care AGM, May 2003: Medical termination of pregnancy in the late first trimester.

In the UK, mifepristone and gemeprost are licensed for medical termination of pregnancy (TOP) in the first trimester up to 63 days' amenorrhoea. Current practice, however, is to use low-dose (200 mg) mifepristone and misoprostol. We report a large cohort study using these drugs for medical TOP in the first trimester after 63 days amenorrhoea. Of 415 patients undergoing the procedure, 392 (95%) aborted completely and 96% required only two doses of misoprostol. We conclude that the regime is effective with few complications, however certain safeguards may be necessary for its widespread introduction

Abortifacient Agents, Nonsteroidal↗

Cloned mice derived from embryonic stem cell karyoplasts and activated cytoplasts prepared by induced enucleation.

Our objective was to induce enucleation (IE) of activated mouse oocytes to yield cytoplasts capable of supporting development following nuclear transfer. Fluorescence microscopy for microtubules, microfilaments, and DNA was used to evaluate meiotic resumption after ethanol activation and the effect of subsequent transient treatments with 0.4 micro g/ml of demecolcine. Using oocytes from B6D2F1 (C57BL/6 x DBA/2) donors, the success of IE of chromatin into polar bodies (PBs) was dependent on the duration of demecolcine treatment and the time that such treatment was initiated after activation. Similarly, variations in demecolcine treatment altered the proportions of oocytes exhibiting a reversible compartmentalization of chromatin into PBs. Treatment for 15 min begun immediately after activation yielded an optimized IE rate of 21% (n = 80) when oocytes were evaluated after overnight recovery in culture. With this protocol, 30-50% of oocytes were routinely scored as compartmentalized when assessed 90 min postactivation. No oocytes could be scored as such following overnight recovery, with 66% of treated oocytes cleaving to the 2-cell stage (n = 80). Activated cytoplasts were prepared by mechanical removal of PBs from oocytes whose chromatin had undergone IE or compartmentalization. These cytoplasts were compared with mechanically enucleated, metaphase (M) II cytoplasts whose activation was delayed in nuclear transfer experiments using HM-1 embryonic stem cells. Using oocytes from either B6D2F1 or B6CBAF1 (C57BL/6 x CBA) donors, the in vitro development of cloned embryos using activated cytoplasts was consistently inferior to that observed using MII cytoplasts. Live offspring were derived from both oocyte strains using the latter, whereas a single living mouse was cloned from activated B6CBAF1 cytoplasts.

Animals↗

Randomised trial of endoscopy with testing for Helicobacter pylori compared with non-invasive H pylori testing alone in the management of dyspepsia.

OBJECTIVE: To compare the efficacy of non-invasive testing for Helicobacter pylori with that of endoscopy (plus H pylori testing) in the management of patients referred for endoscopic investigation of upper gastrointestinal symptoms. DESIGN: Randomised controlled trial with follow up at 12 months. SETTING: Hospital gastroenterology unit. PARTICIPANTS: 708 patients aged under 55 referred for endoscopic investigation of dyspepsia, randomised to non-invasive breath test for H pylori or endoscopy plus H pylori testing. MAIN OUTCOME MEASURE: Glasgow dyspepsia severity score at one year. Use of medical resources, patient oriented outcomes, and safety were also assessed. RESULTS: In 586 patients followed up at 12 months the mean change in dyspepsia score was 4.8 in the non-invasive H pylori test group and 4.6 in the endoscopy group (95% confidence interval for difference -0.7 to 0.5, P=0.69). Only 8.2% of patients followed up who were randomised to breath test alone were referred for subsequent endoscopy. The use of non-endoscopic resources was similar in the two groups. Reassurance value, concern about missed pathology, overall patient satisfaction, and quality of life were similar in the two groups. The patients found the non-invasive breath test procedure less uncomfortable and distressing than endoscopy with or without sedation. No potentially serious pathology requiring treatment other than eradication of H pylori was missed. CONCLUSION: In this patient group, non-invasive testing for H pylori is as effective and safe as endoscopy and less uncomfortable and distressing for the patient. Non-invasive H pylori testing should be the preferred mode of investigation.

Adolescent↗

Effect of pregnancy and obstructive jaundice on inflammatory diseases: the work of P S Hench revisited.

Hench considered that cortisone improved inflammatory joint symptoms during pregnancy and obstructive jaundice. However, the improved symptoms are probably due to changes in the proportions of fatty acids in plasma and inflammatory cell phospholipids. These changes decrease the superoxide anions and eicosanoids produced and also reduce tumour necrosis factor alpha production.

Adrenal Cortex Hormones↗

Characterization of Spiroplasma citri adhesion related protein SARP1, which contains a domain of a novel family designated sarpin.

Transmission of the plant pathogen Spiroplasma citri by its leafhopper vector, Circulifer tenellus, involves adherence to and invasion of insect host cells. The S. citri adhesion related protein P89 (SARP1) was purified by immunoprecipitation using anti-SARP1 monoclonal antibodies. The protein's N-terminal amino acid sequence was determined and used to design a degenerate oligonucleotide. The labeled oligonucleotide hybridized to a 3.5 kb MboI fragment from S. citri DNA, which was then cloned and sequenced. Additionally, a 1.9 kb RsaI fragment of S. citri DNA, partially overlapping the MboI fragment, was isolated and characterized. Sequence analysis of the two clones revealed four open reading frames. ORF1 (675 bp) encodes the C-terminal part of a Soj-like protein. ORFs 1 and 2 were separated from ORFs 3 and 4 by a putative transcription termination site, indicated by a hairpin structure. ORF3 encodes an amphiphilic 798 amino acid long protein with a cleavable signal peptide and a predicted transmembrane helix near the C-terminus. The mature protein of 85.96 kDa has a calculated pI value of 5.5 and has an N-terminal amino acid sequence consistent with that determined from the purified SARP1. At the N-terminus of this protein is a region consisting of six repeats, each 39-42 amino acids, a motif belonging to a previously unrecognized family of repeats found in a variety of bacterial proteins. The taxonomically spotty presence of this 'sarpin' domain and the relationship of the repeats to each other suggests a convergent evolution in multiple lineages.

Amino Acid Sequence↗

Assessment of tolerant sunfish populations (Lepomis sp.) inhabiting selenium-laden coal ash effluents. 3. Serum chemistry and fish health indicators.

Sunfish were collected from fly ash discharge-receiving streams to assess the possible effects of exposure to elevated selenium. Concentrations of selenium, copper, and arsenic were statistically higher in fish tissue (liver) samples from effluent-exposed fish than in reference fish. Several biomarkers were indicative of metal exposure and effect. Plasma protein levels and cholesterol levels were significantly lower in exposed fish, indicating nutritional stress. Ion levels (i.e., K) increased with exposure to ash pond metals, indicating possible gill damage. Fish from the receiving streams also had increased serum glucose and osmolality indicating possible acute stress due to sampling. Fish health assessments revealed a lower incidence of fin erosion, kidney discoloration, urolithiasis or nephrocalcinosis, liver discoloration, and parasites in exposed fish and a higher incidence of skin, eye, and gill aberrations. Condition factors of exposed fish were correlated with biomarker response and were the same as or lower than those of reference fish, but not related to selenium levels. Although several serum biochemical indicators differed between the ash pond-receiving stream and reference sites, pollutant exposure was apparently not sufficient to cause functional damage to critical organ systems.

Adaptation, Physiological↗

Social reasoning: a source of influence on aggression.

Aggressive children show deficits and biases in their social information processing. Cognitions based on early experience and social schemas are also related to development and maintenance of aggressive behavior. Social reasoning can be linked to these aspects of social cognition, impacting on the situational cues individuals encode, their interpretations of events, and influencing response decisions. Past experience also influences development of social reasoning and social schema. Despite this, current discussion of the links between cognition and aggression rarely involves consideration of the influence of social reasoning. In this review, domain theory (E. Turiel, 1978, 1983) underpins an examination of links between social reasoning and aggression using empirical evidence drawn from research on the social reasoning of normal and aggressive children. Children as young as 3 appear to use consistent patterns of social reasoning when making judgments about transgressions and other social events, and these patterns are linked to social reasoning domains. We propose that aggressive children access information from the underlying social reasoning domains differently than their prosocial peers. This in turn affects their decision making and subsequent behavior in social situations. Our review explores developmental and clinical implications of the proposal and provides directions for future research.

Aggression↗