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Biomedical subjects

A Ellis

Publications and source records attributed to A Ellis.

At least 37 records · Page 2Linked to original sources
PubMed2000

Differential actions of L-cysteine on responses to nitric oxide, nitroxyl anions and EDRF in the rat aorta.

1. The effects of L-cysteine were tested in rat aortic rings on responses to nitric oxide free radical (NO(*)), nitroxyl (NO(-)) derived from Angeli's salt and endothelium-derived relaxing factor (EDRF) activated by acetylcholine, ATP and the calcium ionophore A23187. Concentrations of 300 microM or less of L-cysteine had no effect on responses. 2. Relaxations produced by exogenous NO(*) (0.25 - 2.5 microM) were markedly prolonged and relaxations produced by sodium nitroprusside (0.001 - 0.3 microM) were enhanced by 1 and 3 mM L-cysteine. The enhancements by L-cysteine of responses to NO(*) and sodium nitroprusside may be attributed to the formation of S-nitrosocysteine. 3. Relaxations mediated by the nitroxyl anion (0.3 microM) donated from Angeli's salt were more prolonged than those produced by NO(*), and nitroxyl-induced relaxations were reduced by L-cysteine (1 and 3 mM). 4. EDRF-mediated relaxations produced by acetylcholine (0.01 - 10 microM), ATP (3 - 100 microM) and the calcium ionophore A23187 (0.1 microM) were significantly reduced by 3 mM L-cysteine. 5. The similarity between the inhibitory effects of L-cystei on responses to EDRF and on those to nitroxyl suggests that a component of the response to EDRF may be mediated by nitroxyl anion.

Acetylcholine↗
PubMed1999

Envoplakin, a possible candidate gene for focal NEPPK/esophageal cancer (TOC): the integration of genetic and physical maps of the TOC region on 17q25.

Focal nonepidermolytic palmoplantar keratoderma (NEPPK), or tylosis, is an autosomal, dominantly inherited disorder of the skin that manifests as focal thickening of the palmar and plantar surfaces. In three families studied, the skin disorder cosegregates with esophageal cancer and oral lesions. New haplotype analysis, presented here, places the tylosis esophageal cancer (TOC) locus between D17S1839 and D17S785. Envoplakin (EVPL) is a protein component of desmosomes and the cornified envelope that is expressed in epidermal and esophageal keratinocytes and has been localized to the TOC region. Mutation analysis of EVPL in the three affected families failed to show tylosis-specific mutations, and haplotype analysis of three intragenic sequence polymorphisms of the EVPL gene placed it proximal to D17S1839. Confirmation of the exclusion of EVPL as the TOC gene by location was obtained by integration of the genetic and physical mapping data using radiation hybrid, YAC, BAC, and PAC clones. This new physical map will allow further identification of candidate genes underlying NEPPK associated with esophageal cancer, which may also be implicated in the development of sporadic squamous cell esophageal carcinoma and Barrett's adenocarcinoma.

Base Sequence↗
PubMed1999

Spuriously elevated plasma calcitonin in a patient with a thyroid nodule not associated with medullary thyroid carcinoma.

An increase in plasma calcitonin concentration is widely regarded as a specific and sensitive indication of underlying medullary thyroid carcinoma (MTC). We present a case in which the association of increased plasma calcitonin concentration and a thyroid nodule was not due to MTC. Subsequent measurement of plasma calcitonin by a variety of methods highlighted the variability that exists in calcitonin measurement and the potential for clinically misleading results. The rationale for investigation and treatment of MTC, including a recommendation to screen all patients with thyroid nodules using plasma calcitonin measurement, is based on the use of specific two-site calcitonin assays which are not universally used in the UK or USA.

Biomarkers↗
PubMed1999

Serum growth hormone measurements in clinical practice: An audit of performance from the UK National External Quality Assessment scheme.

The replacement of growth hormone (GH) radioimmunoassays with a variety of more specific immunometric methods in diagnostic service laboratories has led to a worsening of between-laboratory agreement, reflecting differences in method bias. Incorrect calibration and differences in specificity are important causes of method bias, but the impact of this on interpretation is not clear. In order to maximize the diagnostic reliability of GH testing for small stature, manufacturers should carefully calibrate their methods against the appropriate GH International Standard, and should use antibodies of broadly agreed specificity. Laboratories performing GH tests should participate in a reliable External Quality Assessment (EQA) scheme and guidelines for investigation that incorporate normal GH responses should be agreed.

Calibration↗
PubMed1998

Identification and characterization of a monocarboxylate transporter (MCT1) in pig and human colon: its potential to transport L-lactate as well as butyrate.

1. Oligonucleotide primers based on the human heart monocarboxylate transporter (MCT1) cDNA sequence were used to isolate a 544 bp cDNA product from human colonic RNA by reverse transcription-polymerase chain reaction (RT-PCR). The sequence of the RT-PCR product was identical to that of human heart MCT1. Northern blot analysis using the RT-PCR product indicated the presence of a single transcript of 3.3 kb in mRNA isolated from both human and pig colonic tissues. Western blot analysis using an antibody to human MCT1 identified a specific protein with an apparent molecular mass of 40 kDa in purified and well-characterized human and pig colonic lumenal membrane vesicles (LMV). 2. Properties of the colonic lumenal membrane L-lactate transporter were studied by the uptake of L-[U-14C]lactate into human and pig colonic LMV. L-Lactate uptake was stimulated in the presence of an outward-directed anion gradient at an extravesicular pH of 5.5. Transport of L-lactate into anion-loaded colonic LMV appeared to be via a proton-activated, anion exchange mechanism. 3. L-Lactate uptake was inhibited by pyruvate, butyrate, propionate and acetate, but not by Cl- and SO4(2-). The uptake of L-lactate was inhibited by phloretin, mercurials and alpha-cyano-4-hydroxycinnamic acid (4-CHC), but not by the stilbene anion exchange inhibitors, 4,4'-diisothiocyanostilbene-2, 2'-disulphonic acid (DIDS) and 4-acetamido-4'-isothiocyanostilbene-2, 2'-disulphonic acid (SITS). 4. The results indicate the presence of a MCT1 protein on the lumenal membrane of the colon that is involved in the transport of L-lactate as well as butyrate across the colonic lumenal membrane. Western blot analysis showed that the abundance of this protein decreases in lumenal membrane fractions isolated from colonic carcinomas compared with that detected in the normal healthy colonic tissue.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1998

Effect of xanthine oxidase inhibition on endothelium-dependent and nitrergic relaxations.

The effects of inhibition of xanthine oxidase on responses mediated by nitric oxide (NO) were examined using the selective xanthine oxidase inhibitors allopurinol and 4-amino-6-hydroxypyrazolo[3,4-d]pyrimidine (AHPP). In rat aortic rings precontracted with phenylephrine (1 microM), allopurinol (300 microM) and AHPP (100, 300 microM) significantly reduced tone, an effect not seen after inhibition of NO synthase with Nomega-nitro-L-arginine (NOLA 100 microM). Relaxations produced by acetylcholine (0.01-10 microM) were significantly enhanced by AHPP (100, 300 microM) but not by allopurinol. Nitrergic relaxations in the rat anococcygeus muscle (field stimulation 1 ms pulses; 1 Hz: 10 s) were not affected by either allopurinol or AHPP. However, relaxations produced by exogenous NO (0.25 microM) were significantly enhanced by AHPP, allopurinol (100 microM) and superoxide dismutase (100 U/ml). Xanthine (500 microM) partially, but significantly, reversed the enhancement produced by AHPP. These findings suggest that superoxide generated by xanthine oxidase modulates the activity of basal and stimulated NO derived from the rat aortic endothelium, but does not affect the activity of the nitrergic transmitter in the rat anococcygeus muscle, despite its ability to modulate responses to exogenous NO.

Acetylcholine↗
PubMed1998

The characterization of butyrate transport across pig and human colonic luminal membrane.

1. Luminal membrane vesicles (LMV) were isolated from human and pig colonic tissues. They were characterized in terms of purity and ability to transport [14C]butyrate. 2. The activity of cysteine-sensitive alkaline phosphatase, and the abundance of villin, NHE2 and NHE3 proteins, markers of the colonic luminal membrane, were significantly enriched in the LMV compared with the original cellular homogenate. The LMV were free from contamination by other cellular organelles and basolateral membranes, as revealed by the negligible presence of either specific marker enzyme activity or characteristic immunogenic protein. 3. The transport of butyrate into the luminal membrane vesicles was enhanced 5-fold at pH 5.5 compared with pH 8.0. Butyrate transport was temperature dependent, and was stimulated in the presence of an outward-directed anion gradient in the order of butyrate > bicarbonate > propionate > chloride. Kinetic analysis of increasing substrate concentration showed saturation kinetics with an apparent Km value of 14.8 +/- 3.6 mM and a Vmax of 54 +/- 14 nmol min-1 (mg protein)-1. 4. Butyrate transport was significantly reduced in the presence of short chain fatty acids (SCFA), acetate, propionate and other monocarboxylates (pyruvate and L-lactate). Butyrate uptake was inhibited by several cysteine group modifying reagents such as p-chloromercuribenzosulphonic acid (pCMBS), p-chloromercuribenzoate (pCMB), mersalyl acid and HgCl2, but not by the stilbene anion exchange inhibitors, 4,4'-diisothiocyanostilbene-2,2'-disulphonate (DIDS) and 4,4'-dinitrostilbene-2,2'-disulphonate (SITS). 5. The described properties of butyrate transport across the luminal pole of the colon suggest the involvement of a carrier protein, in the form of a pH-activated anion exchange process. The transporter is distinct from the erythrocyte band-3 type anion exchanger and may belong to the monocarboxylate-type transport proteins (MCT1).

Animals↗
PubMed1998

Psychological consequences of road traffic accidents in children.

Questionnaire information about possible psychological changes in the months following their accident was obtained for 45 school age children who had attended an Accident and Emergency Department because of their involvement in road traffic accidents. Central nervous system involvement was rare in this group. Short-term psychological consequences were common, but even after 4-7 months 33% were considered by their parents to still have a moderate reaction and a further 11% were considered to be severely affected. The children had high levels of post-traumatic stress symptoms, particularly avoidance in over 50%. Travel anxiety was described in 39%, 23% were depressed and 14% highly anxious--features which were considered by parents to have appeared following the accident, often with increasing disturbance over time. Other apparent repercussions were nightmares and other sleep difficulties in 17%, accident related fears, irritability, anger and emotionally regressed behaviour. As head injury was very uncommon in this series, such psychological consequences were attributable to non-neurological factors. Parents had become more protective of their children and placed greater restrictions on their travel, causing conflict. Younger children, those who had not fully recovered from their accident injuries, and children who also had a parent involved in the same accident, were most at risk. Greater awareness of these psychological consequences of road traffic accidents is required on the part of parents and professionals. Prospective studies are also needed to delineate more precisely those at greatest risk and to assess the effectiveness of treatment approaches.

Accidents, Traffic↗
PubMed1998

A community outbreak of Salmonella berta associated with a soft cheese product.

In September 1994, a complaint was registered at a public health unit concerning a cheese product. In addition, public health laboratories in Ontario reported an increase in the number of isolates of Salmonella berta from patients with diarrhoeal illness. A clinical, environmental and laboratory investigation was initiated to determine the nature of this outbreak. Isolates of Salmonella berta were compared using large fragment genomic fingerprinting by pulsed-field gel electrophoresis (PFGE). By late October, 82 clinical cases had been identified including 35 confirmed, 44 suspected and 3 secondary. The investigation linked illness to consumption of an unpasteurized soft cheese product produced on a farm and sold at farmers' markets. Subtyping results of patient, cheese and chicken isolates were indistinguishable, suggesting that the cheese was contaminated by chicken carcasses during production. The outbreak illustrates the potential role of uninspected home-based food producers and of cross-contamination in the transmission of foodborne bacterial pathogens.

Adolescent↗
PubMed1998

Population-based analysis of 10,766 hospitalizations for mandibular fractures in California, 1991 to 1993.

BACKGROUND: This study describes mandibular fracture incidence, causes, and consequences in a large population. METHODS: California hospital discharge data from 1991 to 1993 were examined to describe causes, lengths of stay, and hospital charges for patients hospitalized for mandibular fractures. Rates were calculated per 100,000 population. RESULTS: There were 10,766 discharges with mandibular fracture as principal diagnosis or as diagnoses two through five on the discharge record (rate=11.5). Of these, 2,694 had mandibular fracture as the only diagnosis (principal diagnosis). For all 10,766 cases, assaults were responsible for more than half (54.0%) of all admissions for mandibular fracture. The highest rates were found among males (18.7), blacks (43.0), and adults aged 16 to 20 (26.5). Charges for the initial hospitalization (excluding physician's fees) for the 2,694 cases with only a diagnosis of mandibular fracture were used to estimate mean charges ($8,740). The total extrapolated 1993 inflation-adjusted hospital charges for mandibular fractures were $34 million per year. Most patients' bills were submitted to government payers, such as Medicaid. CONCLUSION: Treatment of mandibular fractures represents a considerable cost to public-supported programs as well as to patients.

Adolescent↗
PubMed1998

Variation in biochemical screening for Down's syndrome in the United Kingdom.

A questionnaire survey was undertaken of all 73 laboratories performing Down's syndrome screening in 1995. An estimated 352,000 tests were performed representing 47% of maternities. Three-quarters of these tests have ultrasound dating information at the time of testing. The majority of laboratories (70%) commenced screening at 15 weeks of gestation or later, and there was considerable variation in the upper limit of screening (17 to 24 weeks). Eighty-six percent of laboratories screened all women regardless of age. The reported Down's syndrome risk was based on term in 85% of laboratories. There was an inconsistent approach to determining and reporting high risk for trisomy 18 (Edwards' syndrome): 5% reported risks on report forms and 42% notified the clinicians if the risk was considered to be raised.

Age Factors↗
PubMed1998

Development and evaluation of an information booklet for adult survivors of cancer in childhood. The United Kingdom Children's Cancer Study Group Late Effects Group.

AIMS: To determine the need for information among survivors of childhood cancer, to assess the acceptability of an information booklet, and to investigate the effectiveness of the booklet in increasing knowledge and influencing health related behaviours. SUBJECTS: Fifty survivors of childhood cancer (age range 14-32 years) who were consecutive attendees at a long term follow up clinic. METHODS: The booklet was developed for young people aged 14 years and above by the United Kingdom Children's Cancer Study Group Late Effects Group. Included is information about treatment of cancer, general advice about a healthy lifestyle, the rationale for long term follow up, and information about employment and life insurance problems. Survivors were interviewed at the follow up clinic, offered the booklet, and contacted approximately one week later for a telephone interview. The clinic interview assessed survivor's understanding of their illness and treatment and its impact on their lives, and their preferences for further information. The telephone interview determined survivors' general reaction to the booklet, whether it increased knowledge and influenced health related behaviours. RESULTS: All those interviewed accepted the written information and agreed to a follow up interview. Survivors were enthusiastic about being given more information. Over three quarters learned new information from the booklet. There were no indications that the information was associated with anxiety for any demographic or clinical subgroups. After reading the booklet there was an increased awareness of the risk from sunbathing (p < 0.05), and greater appreciation of the importance of follow up (p < 0.05). CONCLUSIONS: These results suggest that written information is likely to be an acceptable and effective supplement to discussions with medical professionals and may readily be incorporated into long term follow up clinics.

Adolescent↗
PubMed1997

Outbreak of viral gastroenteritis due to a contaminated well. International consequences.

CONTEXT: Small round-structured viruses (SRSVs) are known to cause viral gastroenteritis, but until now have not been confirmed in the implicated vehicle in outbreaks. OBJECTIVE: Investigation of a gastroenteritis outbreak. DESIGN: After applying epidemiologic methods to locate the outbreak source, we conducted environmental and laboratory investigations to elucidate the cause. SETTING: Tourists traveling by bus through Alaska and the Yukon Territory of Canada. PARTICIPANTS: Staff of a restaurant at a business complex implicated as the outbreak source, convenience sample of persons on buses that had stopped there, and bus employees. MAIN OUTCOME MEASURES: Odds ratios (ORs) for illness associated with exposures. Water samples from the restaurant and stool specimens from tourists and restaurant staff were examined by nucleic acid amplification using reverse transcription polymerase chain reaction and sequencing of viral amplification products. RESULTS: The itineraries of groups of tourists manifesting vomiting or diarrhea were traced back to a restaurant where buses had stopped 33 to 36 hours previously. Water consumption was associated with illness (OR, 5.3; 95% confidence interval [CI], 2.3-12.6). Eighteen of 26 employees of the business complex were ill; although not the index case, an employee ill shortly before the outbreak lived in a building connected to a septic pit, which was found to contaminate the well supplying the restaurant's water. Genotype 2/P2B SRSV was identified in stool specimens of 2 tourists and 1 restaurant employee. Stools and water samples yielded identical amplification product sequences. CONCLUSIONS: The investigation documented SRSVs in a vehicle epidemiologically linked to a gastroenteritis outbreak. The findings demonstrate the power of molecular detection and identification and underscore the importance of fundamental public health practices such as restaurant inspection, assurance of a safe water supply, and disease surveillance.

Base Sequence↗