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Biomedical subjects

L Johnson

Publications and source records attributed to L Johnson.

At least 19 recordsLinked to original sources
PubMed2007

Protein kinases and their therapeutic exploitation.

This review focuses on the recognition properties of protein kinases at the molecular level. Phosphorylation of the substrate protein by a protein kinase can result in enzyme activation or inhibition, conformational changes that change recognition properties, or the creation of a surface with distinct binding properties. Protein kinases have become important targets for the development of inhibitors with potential therapeutic application. Various examples are considered in this review, and I discuss our own work on glycogen phosphorylase and phosphorylase kinase, and the structures of proteins involved with the cell cycle, including cyclins and cyclin-dependent kinases.

Animals↗
PubMed2006

The safety and immunogenicity of Bacillus Calmette-Guérin (BCG) vaccine in European badgers (Meles meles).

European badgers (Meles meles) are a wildlife reservoir for Mycobacterium bovis (M. bovis) in Great Britain (GB) and the Republic of Ireland and therefore constitute a potential source of infection for cattle. Reduction of badger densities in the Republic of Ireland has resulted in an associated reduction in the risk of a herd break-down with bovine tuberculosis and a study to determine whether this is also the case in GB has been running since 1997. If badgers are a significant source of M. bovis infection for cattle, vaccinating badgers with Bacillus Calmette-Guérin (BCG) might prove to be a long term, cost-effective strategy for controlling bovine tuberculosis whilst preserving badger populations. As a first step towards BCG vaccination of wild badgers, it was necessary to demonstrate safety of the vaccine in captive badgers. Therefore, captive badgers were vaccinated with a commercial source of BCG that is already licensed for administration to humans in GB-BCG Danish SSI. Using a protocol prescribed by the Veterinary Medicines Directorate (VMD) of GB, badgers were vaccinated with two consecutive doses of BCG via either the subcutaneous (s.c.) or intra-muscular (i.m.) routes. The first dose was high, ranging from 16 to 22 x 10(7) colony-forming units (CFU), and was followed 15 weeks later by a lower dose in the range of 4-7 x 10(5)CFU. Local reaction at the site of injection and general responses (body temperature, haematology and blood serum chemistry), behaviour and excretion of BCG were monitored for 28 weeks from the time of the first vaccination. The only side-effect observed was the occurrence of localised swelling at the site of BCG injection that disappeared 48 days after i.m. vaccination but persisted longer in the group vaccinated by the s.c. route. Immunological responses were measured at regular intervals. Strong cellular responses were observed 13 days after the first vaccination, which persisted for 76 days. The lower dose induced a weaker and shorter-lived response.

Animals↗
PubMed2006

Outpatient angioplasty and stenting facilitated by percutaneous arterial suture closure devices.

AIM: To review our practice of outpatient percutaneous vascular interventions facilitated by an arterial suture device. MATERIALS AND METHODS: A retrospective review of all patients attending this tertiary centre for iliac or femoral intervention was undertaken between February 2001 and December 2004. All patients who underwent angioplasty or stenting had their puncture sites closed using a Perclose suture. Patients were kept flat for 15min and allowed to fully mobilize at 60min. Puncture sites were scored for visible bruising, haematoma and pain at discharge and on outpatient follow-up. Patient preference for future outpatient treatment was assessed. RESULTS: Fifty-seven outpatients underwent 81 punctures. Forty-eight (84%) patients underwent iliac angioplasty; of those 42% underwent stent placement. Six patients (10%) required inpatient admission, five secondary to failed suture deployment. One patient had a non-closer-related puncture site intimal flap occlusion successfully repaired at surgery. Fifty-one (90%) patients discharged with a mean time of 157min (60-280min). Forty-six (92%) patients had no visible bruising or palpable haematoma on discharge. No patient had a haematoma greater than 2.5cm. No discharged patient required readmission. Thirty percent reported a moderate to severe groin pain score (2-5/5) at discharge, increasing to 40% at follow-up. Forty-seven (98%) of the 48 patients, who expressed a preference, would be happy to undergo outpatient treatment again. CONCLUSION: Outpatient treatment is feasible, well tolerated and preferable to patients, but 10% will require inpatient admission. A planned post-procedure analgesia regimen or advice should be considered.

Adult↗
PubMed2006

Influence of colostrum deprivation and concurrent Cryptosporidium parvum infection on the colonization and persistence of Escherichia coli O157 : H7 in young lambs.

Escherichia coli O157 : H7 and Cryptosporidium parvum infections of man have been associated with direct contact with small ruminants. Colostrum protects neonates against gastrointestinal pathogens, and orphan lambs, which are common on petting farms, may be deprived of this protection. In a recent study, it was demonstrated that high shedding of E. coli O157 : H7 by an 8-week-old goat kid was associated with coincidental C. parvum infection. Furthermore, both pathogens were co-located in the distal gastrointestinal tract. It was hypothesized that colostrum deprivation and pre-infection with C. parvum predisposed young ruminants to colonization and increased shedding of E. coli O157 : H7. To test this, 21 lambs 5 weeks of age were divided into four groups as follows: (A) colostrum-deprived and inoculated with E. coli O157 : H7, (B) colostrum-deprived and inoculated with C. parvum and then E. coli O157 : H7, (C) conventionally reared and inoculated with E. coli O157 : H7, (D) conventionally reared and inoculated with C. parvum and then E. coli O157 : H7. C. parvum was detected between 8 and 12 days post-inoculation in most of the infected lambs. At 24 h post-inoculation with E. coli O157 : H7, all lambs were shedding between 5 x 10(4) and 5 x 10(7) c.f.u. E. coli O157 : H7 per gram of faeces. E. coli O157 : H7 was shed in higher numbers in the groups pre-inoculated with C. parvum, whether conventionally reared or colostrum-deprived. Interestingly, for the colostrum-deprived lambs on day 3, a significant difference in shedding of E. coli O157 : H7 was observed (P = 0.038), with the lambs inoculated with E. coli alone yielding higher counts than those pre-inoculated with C. parvum. From day 15 onwards, shedding of E. coli O157 : H7 was highest from the colostrum-deprived C. parvum-infected lambs, then (in descending order of shedding) the colostrum-deprived lambs, the conventionally reared lambs infected with C. parvum, and the conventionally reared animals. In total, four animals were euthanized, two at 24 h and two at 96 h post inoculation with E. coli O157 : H7 (two conventionally reared and two colostrum-deprived). All animals euthanized were from groups pre-inoculated with C. parvum prior to challenge with E. coli O157 : H7. On examination of tissues, in three of the four animals examined, multifocal attaching and effacing lesions were observed in the caecum, colon, rectum and at the recto-anal junction, and were confirmed by immunohistochemistry to be associated with E. coli O157 : H7.

Animals↗
PubMed2006

Podcasts--an emerging form of digital publishing.

Podcasting has recently emerged as an important information technology tool for health professionals and consumers around the world. Prestigious journals, international conferences, universities and government agencies among other entities are starting to publish digital informotion via audio and video podcasts. Podcosting is distinguished from other forms of digital audio-video content because it can be subscribed to (using Real Simple Syndication or RSS) and easily accessed from a personal computer. Further, it can be downloaded to a mobile device, such as an iPod where the user is able to listen to or watch it anywhere, anytime. Podcosting is used in new and evolving ways to publish information for healthcare education, patient care, professional continuing education, and in support of healthcare research. In addition to a description of what podcasting is, how podcasts are created, and how they are used, this paper addresses four critical issues that are emerging concerning podcasts. These issues are intellectual property and copyright, podcast preservation, podcast location, and podcast standards. As podcasting matures and new uses are discovered, we will see podcasting incorporated into our education, research and patient care publication paradigm.

Computers, Handheld↗
PubMed2005

Advanced granulomatous lesions in Mycobacterium bovis-infected cattle are associated with increased expression of type I procollagen, gammadelta (WC1+) T cells and CD 68+ cells.

The pathognomonic characteristic of tuberculosis (TB) is the formation of a tuberculous granuloma. The objective of this study was to classify lymph node granulomas from experimentally infected calves into different histopathological stages and characterize them further by studying cell types and markers of fibrosis associated with each of the stages. Four stages of granuloma were identified and mRNA and protein expression for cell markers, cytokines and pro-fibrotic markers were studied by immunohistochemistry (IHC) and in-situ hybridization (ISH). In advanced stage granulomas, there was an increase in the expression of TGF-beta, and of type I procollagen as demonstrated by IHC and ISH. As the granulomas advanced, there were fewer CD3+T cells and they tended to be more prominent towards the periphery of the lesions, with a steady increase in the number of CD68+ cells and gammadelta (WC1+) T cells. Granuloma classification and application of cell cytokine markers will assist in improving understanding of the pathogenesis of bovine TB and may help to identify the immunopathology of active disease versus contained or inactive disease. Such disease correlates may help to inform the development of improved diagnostic methods and support vaccine development programmes.

Animals↗
PubMed2005

Fast recruiting clinical trials--a utopian dream or logistical nightmare?

Randomised clinical trials that exceed anticipated recruitment rates will by definition have the necessary precision to answer the research question within the expected time, thus ensuring the timely release of data that will inform future clinical practice. In addition, the national or international momentum generated brings with it a collective sense of achievement. Such trials, however, may also identify logistical and scientific problems that researchers should be aware of and for which provision needs to be made. The logistical problems relate to the rapid identification of the extra resources required to allow continued excellence in day-to-day management and monitoring of trial governance (both in participating centres and in coordinating trials units). The scientific/clinical problems include managing issues such as unexpected toxicities and suboptimal compliance, and the lack of time available in a rapidly recruiting trial to address them. A related issue concerns the lack of time available to initiate substudies (e.g. biological substudies), the relevance of which may only become apparent as the trial progresses. Many of these challenges were highlighted by recent experience with the Cancer Research UK Taxotere as Adjuvant Chemotherapy trial.

Clinical Trials as Topic↗
PubMed2005

Meta-analysis of five genome-wide linkage studies for body mass index reveals significant evidence for linkage to chromosome 8p.

OBJECTIVE: To perform a meta-analysis of genome-wide linkage scans using body mass index (BMI) to identify genetic loci predisposing to obesity. DATA: A total of 13 published genome scans on obesity have used BMI as their primary end point. Five of these 13 groups agreed to provide detailed results from their scans that were required for a meta-analysis. Collectively, these five studies included a total of 2814 individuals from 505 families. METHODS: The results of the five studies were analysed using the GSMA (genome scans meta-analysis) method. RESULTS: The analysis revealed significant evidence for linkage of the quantitative phenotype BMI to 8p (P<0.0005).

Adult↗
PubMed2005

Colonization of 8-week-old conventionally reared goats by Escherichia coli O157 : H7 after oral inoculation.

Enterohaemorrhagic Escherichia coli O157 : H7 infections of man have been associated with consumption of unpasteurized goat's milk and direct contact with kid goats on petting farms, yet little is known about colonization of goats with this organism. To assess the contribution of flagella and intimin of E. coli O157 : H7 in colonization of the goat, 8-week-old conventionally reared goats were inoculated orally in separate experiments with 1x10(10) c.f.u. of a non-verotoxigenic strain of E. coli O157 : H7 (strain NCTC 12900 Nal(r)), an aflagellate derivative (DMB1) and an intimin-deficient derivative (DMB2). At 24 h after inoculation, the three E. coli O157 : H7 strains were shed at approximately 5x10(4) c.f.u. (g faeces)(-1) from all animals. Significantly fewer intimin-deficient bacteria were shed only on days 2 (P = 0.003) and 4 (P = 0.014), whereas from day 7 to 29 there were no differences. Tissues from three animals inoculated with wild-type E. coli O157 : H7 strain NCTC 12900 Nal(r) were sampled at 24, 48 and 96 h after inoculation and the organism was cultured from the large intestine of all three animals and from the duodenum and ileum of the animal examined at 96 h. Tissues were examined histologically but attaching-effacing (AE) lesions were not observed at any intestinal site of the animals examined at 24 or 48 h. However, the animal examined at 96 h, which had uniquely shed approximately 1x10(7) E. coli O157 : H7 (g faeces)(-1) for the preceding 3 days, showed a heavy, diffuse infection with cryptosporidia and abundant, multifocal AE lesions in the distal colon, rectum and at the recto-anal junction. These AE lesions were confirmed by immunohistochemistry to be associated with E. coli O157 : H7.

Adhesins, Bacterial↗
PubMed2004

Somatic mutations of KIT in familial testicular germ cell tumours.

Somatic mutations of the KIT gene have been reported in mast cell diseases and gastrointestinal stromal tumours. Recently, they have also been found in mediastinal and testicular germ cell tumours (TGCTs), particularly in cases with bilateral disease. We screened the KIT coding sequence (except exon 1) for germline mutations in 240 pedigrees with two or more cases of TGCT. No germline mutations were found. Exons 10, 11 and 17 of KIT were examined for somatic mutations in 123 TGCT from 93 multiple-case testicular cancer families. Five somatic mutations were identified; four were missense amino-acid substitutions in exon 17 and one was a 12 bp in-frame deletion in exon 11. Two of seven TGCT from cases with bilateral disease carried KIT mutations compared with three out of 116 unilateral cases (P=0.026). The results indicate that somatic KIT mutations are implicated in the development of a minority of familial as well as sporadic TGCT. They also lend support to the hypothesis that KIT mutations primarily take place during embryogenesis such that primordial germ cells with KIT mutations are distributed to both testes.

DNA Mutational Analysis↗
PubMed2004

Molecular flexibility and discontinuous translocation of a non-templated polymerase.

Little is known regarding the translocation of non-templated nucleic acid polymerases with respect to single-stranded primers. VP55, the vaccinia virus poly(A) polymerase, translocates as it processively adds a approximately 3-7 adenylate tail to primers possessing only three ribouridylate residues (as an (rU)(2)-N(15)-rU motif), and a approximately 25-30 adenylate tail to primers that are more U-rich. Here, three models were addressed for the translocation of VP55 with respect to its primer, namely: (a) rigid protein/rigid nucleic acid; (b) flexible protein/rigid nucleic acid; (c) rigid protein/flexible nucleic acid. Analysis of free and covalently VP55-attached primers favored either (b) or a version of (c) incorporating a passive steric block, and suggested two regions of relative motion between polymerase and primer. Inclusion of a 6nt uridylate-rich patch at the primer 3' end switched the polymerase from approximately 3-7 nt to approximately 25-30 nt tail addition without affecting initial binding affinity. By synthesizing this patch as a (rU/dC) pool, discontinuous polymerase movements could be detected.

Polynucleotide Adenylyltransferase↗
PubMed2004

Prevention of percutaneous endoscopic gastrostomy site infections caused by methicillin-resistant Staphylococcus aureus.

Percutaneous endoscopic gastrostomy (PEG) is widely used to maintain enteral nutrition in patients who are unable to swallow. Peristomal wound infection is the most common complication of this procedure. In a hospital endemic for methicillin-resistant Staphylococcus aureus (MRSA), MRSA can be the most common organism associated with these infections. We have evaluated a strategy consisting of screening, skin decontamination and glycopeptide prophylaxis for preventing PEG-site infections. None of the 34 patients who received the decontamination protocol and glycopeptide prophylaxis (Group A) developed PEG-site infections within one month of surveillance. Two patients were infected with MRSA after that period. One of seven patients who received the decontamination protocol alone (Group B) was infected within the period of surveillance, while another patient was infected after that period. Both were infected with MRSA. None of nine patients who received glycopeptide prophylaxis alone (Group C) were infected. The results suggest that the strategy of screening, decontamination and glycopeptide prophylaxis is effective in the prevention of PEG-site infections with MRSA. Further trials are necessary to confirm these findings.

Aged↗
PubMed2004

Detection and strain differentiation of European bat lyssaviruses using in situ hybridisation.

A protocol suitable for the detection of rabies virus and the related European bat lyssaviruses type 1 and 2 is described. In situ hybridisation, employing digoxigenin labelled riboprobes was used for the detection of lyssavirus RNA in mouse-infected brain tissue. The principal advantage of this technique, compared to routine methods used for histopathology, is that this method is robust, highly sensitive, and specific for assessing the presence of RNA in different tissues. An additional advantage is that there is no longer any requirement for high laboratory bio-containment, once the tissue under investigation has been safely fixed. Using this method, both genomic and messenger RNA were detected. The ability to detect messenger RNA is indicative of the presence of replicating virus and therefore, this technique is a powerful diagnostic tool for the routine detection of strains of rabies virus including the European bat lyssaviruses.

Animals↗
PubMed2004

Pharmacokinetics of ceftiofur in llamas and alpacas.

Pharmacokinetic studies of antibiotics in South American camelids are uncommon, therefore drugs are often administered to llamas and alpacas based on dosages established in other domestic species. The disposition of ceftiofur sodium was studied in llamas following intramuscular administration and in alpacas following intravenous and intramuscular administration. Eleven adult llamas were given ceftiofur sodium by intramuscular injection. Each animal received either a standard dose of 2.2 mg/kg or an allometrically scaled dose ranging from 2.62 to 2.99 mg/kg in a crossover design. Ten adult alpacas were given ceftiofur sodium by intravenous and intramuscular injections. Each animal received a standard dosage of 1 mg/kg or an allometrically scaled dose ranging from 1.27 to 1.44 mg/kg i.v., and 1.31-1.51 mg/kg i.m. Blood samples were collected at 0, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, and 72 h after administration of the ceftiofur. Pharmacokinetic parameters of ceftiofur in llamas and alpacas were similar following i.m. dosing at both dose levels. The only differences noted were in the total AUC between dose levels, but the AUC/dose values were not different. A sequence effect was noted in the alpaca data, which resulted in lower AUCs for the second dose when the i.v. dose was given first, and with higher AUCs for the second dose when the i.m. dose was given first. Overall, ceftiofur pharmacokinetics in llamas and alpacas are similar, and also very similar to reported parameters for sheep and goats.

Animals↗
PubMed2004

A multicentre randomised controlled trial of an intervention to improve the accuracy of linear growth measurement.

AIMS: To evaluate linear growth assessment and the effect of an intervention on measurement accuracy in primary care practices (PCP) within eight US geographical areas. METHODS: In this multicentre randomised controlled intervention study, paediatric endocrine nurses as site coordinators (SC) visited 55 randomly assigned PCP to evaluate growth assessment of staff performing linear measurements. SC observed 127 measurers assessing a total of 878 children: 307 (baseline), 282 (3 months), and 289 (6 months). Accuracy was determined by SC re-measuring each child with correct technique and equipment. State of the art equipment and a standardised growth training session were provided to the intervention group (IG) following the baseline visit. SC repeated data collection at all PCP at 3 and 6 months. RESULTS: There were no baseline differences between IG and CG equipment, technique, or accuracy; only 30% of measurements were accurate (< or =0.5 cm from SC). Post-intervention, significantly more IG measurements were accurate: IG = 55%, CG = 37% at 3 months; IG = 70%, CG = 34% at 6 months. Odds ratio of accuracy for IG versus CG was 2.1 at 3 months and 4.5 at 6 months. At 6 months, mean difference from the SC measurements was 0.5 cm in IG and 1.1 cm in CG. CONCLUSIONS: In PCP, children are measured inaccurately. Our intervention significantly improved measurement accuracy. Improved accuracy could yield more rapid detection and diagnosis of paediatric growth disorders.

Adolescent↗
PubMed2004

Using verbal autopsy to identify and proportionally assign cause of death in Ibadan, southwest Nigeria.

Reliable and accurate data remain scarce on the cause and rates of mortality among adults in sub-Saharan Africa. The Idikan Adult Mortality Study, a prospective community-based study was initiated in order to obtain the overall as well as cause-specific mortality data for a community of adults (15 years and above). Standardised verbal autopsy questionnaire was used to investigate and assign the mode and cause of death. There were 232 reported deaths in the baseline population of 4127 adults over 5 years, giving an unadjusted death rate of 11.2 per 1000 per year. Thirty-nine (16.8% ) of these death occurred suddenly. The commonest known cause of death was due to cardiovascular disease, which was responsible for 43 (18.5% ) of all deaths. It was also the commonest known cause of sudden death accounting for 30.8% of such deaths. Infection was responsible for 28 (12.1% ) deaths while injury accounted for 7 (2.6% ) deaths. Subjects, 50 years and above were more likely to die and also die suddenly than were the younger subject (p<0.0001, p<0.0001) and significantly more death occurred in males than females (6.9% versus 4.7% ) (P<0.01). Deaths were also more likely to have occurred at home and outside the hospital, increasing the probability of these deaths being underreported. Following multivariate logistic regression analysis, respondents between the age of 20 -49 years had significantly reduced risk of dying (p=0.029), while cigarette smoking significantly increased the risk of dying (p=0.012). In the absence of the urgently needed vital statistics, use of verbal autopsies is a potentially useful investigative method for identifying and assigning cause of adult deaths in a community.

Adolescent↗
PubMed2003

Nasal bone hypoplasia in trisomy 21 at 15-22 weeks' gestation.

OBJECTIVE: To investigate the potential value of ultrasound examination of the fetal profile for present/hypoplastic fetal nasal bone at 15-22 weeks' gestation as a marker for trisomy 21. METHODS: This was an observational ultrasound study in 1046 singleton pregnancies undergoing amniocentesis for fetal karyotyping at 15-22 (median, 17) weeks' gestation. Immediately before amniocentesis the fetal profile was examined to determine if the nasal bone was present or hypoplastic (absent or shorter than 2.5 mm). The incidence of nasal hypoplasia in the trisomy 21 and the chromosomally normal fetuses was determined and the likelihood ratio for trisomy 21 for nasal hypoplasia was calculated. RESULTS: All fetuses were successfully examined for the presence of the nasal bone. The nasal bone was hypoplastic in 21/34 (61.8%) fetuses with trisomy 21, in 12/982 (1.2%) chromosomally normal fetuses and in 1/30 (3.3%) fetuses with other chromosomal defects. In 3/21 (14.3%) trisomy 21 fetuses with nasal hypoplasia there were no other abnormal ultrasound findings. In the chromosomally normal group hypoplastic nasal bone was found in 0.5% of Caucasians and in 8.8% of Afro-Caribbeans. The likelihood ratio for trisomy 21 for hypoplastic nasal bone was 50.5 (95% CI 27.1-92.7) and for present nasal bone it was 0.38 (95% CI 0.24-0.56). CONCLUSION: Nasal bone hypoplasia at the 15-22-week scan is associated with a high risk for trisomy 21 and it is a highly sensitive and specific marker for this chromosomal abnormality.

Abnormalities, Multiple↗