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Biomedical subjects

N Johnson

Publications and source records attributed to N Johnson.

At least 55 records · Page 3Linked to original sources
PubMed2003

Isolation of a European bat lyssavirus type 2 from a Daubenton's bat in the United Kingdom.

European bat lyssavirus type 2 (EBLV-2) has been isolated once previously from a bat in the UK in June 1996. In September 2002, a Daubenton's bat (Myotis daubentonii) found in Lancashire developed abnormal behaviour, including unprovoked aggression, while it was in captivity. Brain samples from the bat were tested for virus of the Lyssavirus genus, which includes EBLV-2 (genotype 6), and classical rabies virus (genotype 1). A positive fluorescent antibody test confirmed that it was infected with a lyssavirus, and PCR and genomic sequencing identified the virus as an EBLV-2a. Phylogenetic comparisons with all the published sequences from genotype 6 showed that it was closely related to the previous isolate of EBLV-2 in the UK and suggested links to isolates from bats in The Netherlands. The isolation of EBLV-2 from a bat found on the west coast of England provides evidence that this virus may be present within the UK Daubenton's bat population at a low prevalence level.

Amino Acid Sequence↗
PubMed2003

Possible association of the tau H1/H1 genotype with primary progressive aphasia.

The authors screened for tau gene mutations and polymorphisms to determine whether genetic variation at or near the tau locus contributes to the development of primary progressive aphasia (PPA). No mutations were detected in 25 patients with PPA. However, a significant overrepresentation of the tau H1/H1 genotype, also found in progressive supranuclear palsy and corticobasal degeneration, was found in the PPA group. Whether tau haplotypes have a primary causal role or whether they affect the topology of neurodegeneration remains to be determined.

Adult↗
PubMed2003

European bat lyssaviruses: an emerging zoonosis.

In Europe, two bat lyssaviruses referred to as European bat lyssaviruses (EBLVs) types 1 and 2 (genotypes 5 and 6 respectively) which are closely related to classical rabies virus are responsible for an emerging zoonosis. EBLVs are host restricted to bats, and have been known to infect not only their primary hosts but also in rare circumstances, induce spillover infections to terrestrial mammals including domestic livestock, wildlife and man. Although spillover infections have occurred, there has been no evidence that the virus adapted to a new host. Since 1977, four human deaths from EBLVs have been reported. None of them had a record of prophylactic rabies immunization. Only fragmentary data exist about the effectiveness of current vaccines in cross-protection against EBLVs. It is clear that EBLV in bats cannot be eliminated using conventional strategies similar to the control programmes based on vaccine baits used for fox rabies in Europe during the 1980s. Due to the protected status of bats in Europe, our knowledge of EBLV prevalence and epidemiology is limited. It is possible that EBLV is under-reported and that the recorded cases of EBLV represent only a small proportion of the actual number of infected bats. For this reason, any interaction between man and bats in Europe must be considered as a possible exposure. Human exposure through biting incidents, especially unprovoked attacks, should be treated immediately with rabies post-exposure treatment and the bat, where possible, retained for laboratory analysis. Preventative measures include educating all bat handlers of the risks posed by rabies-infected animals and advising them to be immunized. This review provides a brief history of EBLVs, their distribution in host species and the public health risks.

Animals↗
PubMed2003

Generation and analysis of mice with a targeted disruption of the arylamine N-acetyltransferase type 2 gene.

Arylamine N-acetyltransferases (NATs) are polymorphic xenobiotic metabolising enzymes, linked to cancer susceptibility in a variety of tissues. In humans and in mice there are multiple NAT isoforms. To identify whether the different isoforms represent inbuilt redundancy or whether they have unique roles, we have generated mice with a null allele of Nat2 by gene targeting. This mouse line conclusively demonstrates that the different isoforms have distinct functions with no compensatory expression in the Nat2 null animals of the other isoforms. In addition, we have used the transgenic line to show the pattern of Nat2 expression during development. Although Nat2 is not essential for embryonic development, it has a widespread tissue distribution from at least embryonic day 9.5. This mouse line now paves the way for the teratological role of Nat2 to be tested.

Amino Acid Transport System A↗
PubMed2003

Risk factors associated with travel to rabies endemic countries.

Increased travel to exotic destinations around the world is escalating the risk that an emerging virus may be imported into the UK. Rabies should be considered in the differential diagnosis of any encephalitic illness presenting in an appropriate epidemiological context. Molecular diagnostic tests that can rapidly discriminate rabies from other suspected infections will influence the use of anti-rabies prophylaxis for potential contacts with the victim. In 2001, the UK had two confirmed human rabies cases, imported from the Philippines and Nigeria, respectively. In case one, hemi-nested reverse transcriptase polymerase chain reaction (hn-RT-PCR) and automated sequencing confirmed the presence of rabies virus (RABV) within both the saliva and skin specimens within 36 h of sample submission. Subsequent phylogenetic analysis using a partial sequence of the nucleoprotein (N-) gene segment demonstrated that the virus was closely related to that of canine variants currently circulating in the Philippines. In the second case, the fluorescent antibody test and reverse transcriptase polymerase chain reaction (RT-PCR) confirmed the diagnosis on post-mortem tissue. Phylogenetic analysis of two genomic segments of this isolate confirmed that it was a classical RABV (genotype 1) of the Africa 2 subgroup. These cases have highlighted the capability of molecular diagnostic tests for the rapid identification and subsequent genotyping of RABV to host and geographical location. In the first instance, rabies diagnosis often rests on clinical and epidemiological grounds. Negative tests, even late in the illness, do not exclude the diagnosis as these tests are never optimal and are entirely dependent on the nature and quality of the sample supplied. For this reason, rapid molecular detection and virus typing will be essential in considering the appropriate medical treatment regimen for a patient. In addition, an early diagnosis may decrease the number of unnecessary contacts with the patient and reduce the requirement for invasive and costly interventions. Rabies should form part of a differential diagnosis for any patient presenting with a history of travel to a rabies endemic country and displaying an undiagnosed encephalopathy.

Animals↗
PubMed2003

Effects of donepezil on cognitive functioning in Down syndrome.

Our goal in this study was to determine whether donepezil, an acetylcholinesterase inhibitor, would improve cognitive functioning in 19 subjects with Down syndrome and no dementia. They were assigned to either a donepezil or placebo group. Cognitive functioning and caregiver ratings were measured at baseline, 4 weeks, and 12 weeks. With the exception of one area (language), no improvement was noted in any of the cognitive subtests, behavioral scores, or caregiver ratings. Subjects in the donepezil group showed an improvement in language scores compared to subjects in the placebo group. The results suggest that donepezil may improve language performance in subjects with Down syndrome and no dementia, but further studies need to be done on a larger group to confirm this result.

Adolescent↗
PubMed2003

Prenatal diagnosis of cleft lip and palate.

OBJECTIVE: The use of ultrasound for the prenatal diagnosis of cleft lip and palate has aided considerably in the early diagnosis of orofacial clefting. The impact and consequences of this need to be considered as the reliability and validity of ultrasound diagnosis increases. This review article considers a number of these issues as well as up-to-date information on the quality of the technique.

Abortion, Induced↗
PubMed2002

Rabies antibody testing and the UK Pet Travel Scheme.

The Pet Travel Scheme (PETS) commenced on February 28, 2000, allowing pet dogs and cats from named countries to enter the UK without spending six months in quarantine as long as they met specific criteria. Since the start of the scheme to the end of February 2002, more than 45,000 animals have successfully entered the UK under PETS. In this article, Dr Tony Fooks and colleagues consider the results of serological testing under the scheme at the Veterinary Laboratories Agency and look to future developments.

Animals↗
PubMed2002

Cleavage stage versus blastocyst stage embryo transfer in assisted conception.

BACKGROUND: Despite numerous advances in the field of in vitro fertilisation (IVF), many of the widely applied embryo culture techniques and resulting implantation rates have remained relatively unchanged since the first treatment was performed in the mid 1970's. Recent advances in the understanding of nutrient requirements of embryos, have led to a renaissance of extending their culture from the standard procedure of 2-3 days (early cleavage embryo transfer) to 5-6 days (blastocyst culture). The rationale for blastocyst culture is to improve the synchronicity of uterine and embryonic development and provide a mechanism for self-selection of viable embryos. Numerous reports on the clinical benefits of blastocyst culture have led to the worldwide introduction of this technique, despite a deficiency of conclusive evidence to do so. OBJECTIVES: Primary: To determine if blastocyst stage embryo transfers (ET's) result in higher success rates, than cleavage stage embryo transfers. Secondary: To assess the overall embryo utilisation rate of both techniques. SEARCH STRATEGY: Electronic searches of the Cochrane Menstrual Disorders and Subfertility Group specialised register of controlled trials, CCTR, MEDLINE, EMBASE, and Bio extracts were performed to identify relevant randomised controlled trials (RCTs). Attempts were also made to identify trials from the National Research Register, the Clinical Trial Register and the citation lists of review articles and included trials. The first or corresponding author of each included trial was also contacted for additional information. SELECTION CRITERIA: Trials were included if they were randomised and compared the effectiveness of early cleavage versus blastocyst stage transfers. DATA COLLECTION AND ANALYSIS: Of the 29 trials that were identified, ten trials met the inclusion criteria and were reviewed. Primary outcomes were rates of; live birth, clinical pregnancy and implantation per woman. Secondary outcomes were rates of; miscarriage, monozygotic twinning, embryo freezing, embryo utilisation, cancellation, multiple pregnancy and high order pregnancy and per cycle data. Quality assessment and data extraction were performed independently by two reviewers. Meta analysis was performed using odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. MAIN RESULTS: There was no significant difference between the two treatment groups in live birth rate, although this was reported by only one quasi-random trial (Peto OR 1.59, 95% CI 0.80, 3.15). There was also no evidence of a difference in pregnancy rate (both overall and subgroups) between the two groups for pregnancy rate per couple randomised (4 RCTs: Peto OR 0.86, 95% CI 0.57, 1.29). There was also no suggestion of an overall difference in implantation rates per embryo's transferred although it was impossible to calculate valid confidence intervals from published data (Day 2/3 17.1% vs Day 5/6 18.9%). The subgroup of sequential media trials suggested higher implantation rate for blastocyst transfer (Day 2/3 22.6% vs Day 5/6 32%). The miscarriage rate was no different between the two groups (1 RCT, Peto OR 1.66, 95% CI 0.41, 6.81). The RCTs reporting embryo freezing showed no difference (Peto OR 1.71, 95% CI 1.00, 2.94), however the two quasi-random trials showed a significant difference in favour of the Day 2/3 group (Peto OR 2.99, 95% CI 1.88, 4.75). Embryo transfer cancellation rates were significantly higher in the Day 5/6 group (5 RCTs: Peto OR 0.57, 95% CI 0.40, 0.83). There was no significant difference in the rate of multiple pregnancies or the rate of high order pregnancies (3 RCTs, Peto OR 0.58, 95% CI 0.30, 1.12)(2 RCTs, Peto OR 7.88, 95% CI 0.49, 126.30 respectively). REVIEWER'S CONCLUSIONS: Overall this review of the best available evidence based on data from randomised controlled trials, suggests that to date little difference in the major outcome parameters has been demonstrated between early embryo transfer and blastocyst culture. Collectively, the increase in cancellation and the possible decrease in cryopreservation rates suggest that the routine practice of blastocyst culture should be offered to patients with caution. The subgroup of trials employing sequential media, did however demonstrate a substantial improvement in implantation rates and similar pregnancy rates, despite the transfer of less embryos. Whether this trend will culminate in convincing higher live birth rates per woman, has yet to be validated.

Blastocyst↗
PubMed2002

Tubal flushing for subfertility.

BACKGROUND: A possible therapeutic effect of diagnostic tubal patency testing has been debated in the literature for half a century. Further debate surrounds whether oil-soluble or water-soluble contrast media might have the bigger fertility-enhancing effect. Historically a variety of agents have been used to 'flush' the fallopian tubes, although tubal flushing does not currently form part of routine practice in the treatment of fertility delay. OBJECTIVES: To evaluate the effect of flushing a woman's fallopian tubes with oil- or water-soluble contrast media on subsequent pregnancy outcomes in couples with infertility. SEARCH STRATEGY: The search strategy of the Menstrual Disorders and Subfertility Group and a recent search of electronic databases completed in December 2001 was used for the identification of relevant randomised controlled trials. SELECTION CRITERIA: All randomised trials where tubal flushing with oil-soluble contrast media or tubal flushing with water-soluble media was compared with one another or with no treatment were considered for inclusion in the review. DATA COLLECTION AND ANALYSIS: Eight randomised controlled trials were identified and included in this review. A further one randomised controlled trial is ongoing. All trials were assessed for quality criteria. The studied outcomes were pregnancy, live birth (and ongoing pregnancy), miscarriage, ectopic pregnancy, treatment complications including pain, intravasation of contrast medium, infection and haemorrhage, and image quality. MAIN RESULTS: Tubal flushing with oil-soluble media versus no intervention was associated with a significant increase in the odds of pregnancy (OR 3.57, 95%CI 1.76-7.23). There were no data from RCTs to assess tubal flushing with water-soluble media versus no intervention. Tubal flushing with oil-soluble media was associated with a significant increase in the odds of live birth versus tubal flushing with water-soluble media (OR 1.49, 95%CI 1.05-2.11) but the odds of pregnancy showed no significant difference (OR 1.23, 95%CI 0.95-1.60) and there was evidence of statistical heterogeneity for these two outcomes. The addition of oil-soluble media to flushing with water-soluble media (water-soluble plus oil-soluble media versus water-soluble media alone) showed no significant difference in the odds of pregnancy (OR 1.16, 95%CI 0.78-1.70) or live birth (OR 1.06, 95%CI 0.64-1.77). REVIEWER'S CONCLUSIONS: There is some evidence of effectiveness of tubal flushing with oil-soluble contrast media in increasing the odds of pregnancy versus no intervention. The limited evidence of an increase in the odds of live birth from tubal flushing with oil-soluble contrast media versus water-soluble contrast media must be interpreted cautiously. Further robust randomised trials, comparing oil-soluble versus water-soluble media and comparing each versus no intervention, are required to provide convincing evidence as to whether the technique should be accepted into widespread clinical practice.

Contrast Media↗
PubMed2002

Phylogenetic comparison of the genus Lyssavirus using distal coding sequences of the glycoprotein and nucleoprotein genes.

The phylogenetic relationships between all seven genotypes within the genus Lyssavirus were compared at the nucleotide level utilising two distal regions of the viral genome. The resulting analysis of each region produced similar, although not identical, phylogenetic results, suggesting that the evolutionary pressures on individual proteins within the genome vary. These differences are in part due to the increased variability observed within the glycoprotein sequence over the nucleoprotein sequence. Pair-wise comparison using the glycoprotein partial sequence between different isolates demonstrate that within genotypes, viruses show between 80 and 100% sequence identity, whilst between genotypes, viruses show between 50 and 75% identity. This provides a consistent guide to assigning new viruses to existing genotypes. Alignment of the amino acid sequence for the truncated glycoprotein sequence to the Pasteur Virus vaccine strain show significant residue variation between positions 139 and 170. However, residue variation tends to vary with genotype implying that these changes have not evolved due to immunological pressure from the host but have occurred following the separation of viruses into discrete groups. Comparison of the phylogenetic analysis for this partial region of the glycoprotein suggest that it gives comparable results to studies that have used larger regions of the Lyssavirus genome.

Genome, Viral↗
PubMed2002

Canine vaccine recipients recognize an immunodominant region of the rabies virus glycoprotein.

To investigate the immune response to anti-rabies vaccination in the principal recipient (the domestic dog), four truncated fragments of the rabies virus glycoprotein were expressed as glutathione S-transferase fusion proteins. Immune sera from vaccinated rabbits and dogs were then used to probe for reactivity with these expressed proteins. In two rabbits and four dogs tested, the dominant antibody response to non-conformational antigenic sites appeared to be directed to a region of the glycoprotein between amino acids 222 and 332. The N-terminal fragment of the glycoprotein was also significantly antigenic. Further studies to assess whether the antibody response to the internal domain could neutralize the rabies Challenge Virus Standard (CVS) strain, using antibody depletion, suggested that this fraction did contribute to the ability of post-vaccination sera to neutralize and therefore protect against infection.

Animals↗
PubMed2002

A feasibility study of remote monitoring of asthmatic patients.

We assessed the feasibility of a remote monitoring system for asthmatic patients to use in their own homes. Eighty-four patients were invited to participate following discharge from hospital after an acute exacerbation of their asthma. We remotely monitored 33 patients from two hospitals for two weeks. Their mean age was 34 years (range 17-50 years). Patient compliance with monitoring was 80% (range 45-231%) and compliance with transmitting the results using a modem was 52% (range 0-100%). The average time spent teaching patients how to perform measurements was 16 min (range 2-55 min) and time spent providing asthma education was 39 min (range 5-135 min). Ninety-six per cent of patients found the equipment easy or very easy to use and 92% said they would use the equipment again in the future. Medical intervention occurred in 48% of patients during the study period, which suggests that the use of remote monitoring could be important in reducing asthma morbidity and improving treatment outcomes.

Adolescent↗
PubMed2001

Secondary necrosis is a source of proteolytically modified forms of specific intracellular autoantigens: implications for systemic autoimmunity.

OBJECTIVE: Specific autoantigens targeted in systemic autoimmunity undergo posttranslational modifications, such as cleavage, during cell death that could potentially enhance their immunogenicity. In light of the increasing interest in the immunologic consequences of defective clearance of apoptotic cells, we sought to determine whether autoantigens cleaved during apoptosis undergo an additional wave of proteolysis as apoptosis progresses to secondary necrosis in the absence of phagocytosis. METHODS: Apoptosis was induced in Jurkat cells with etoposide, anti-Fas antibody, or staurosporine (STS), and in HeLa cells with STS. Progression to secondary necrosis was assessed morphologically and quantified by trypan blue uptake. Autoantigen proteolysis during cell death was examined by immunoblotting of cell lysates using highly specific human autoantibodies as detecting probes. RESULTS: Cells treated with the different apoptosis inducers underwent a rapid apoptosis that gradually progressed to secondary necrosis. During the initial apoptotic stages, several autoantigens, including poly(ADP-ribose) polymerase, topoisomerase I (or Scl-70), SSB/La, and U1-70 kd, were cleaved into their signature apoptotic fragments. Progression of apoptosis to secondary necrosis was associated with additional proteolysis of these and other autoantigens in a caspase-independent manner. Some autoantigens (e.g., ribosomal RNP, Ku, and SSA/Ro) appeared to be resistant to proteolysis during cell death. CONCLUSION: In the absence of phagocytosis, apoptotic cells may undergo secondary necrosis, a process associated with additional proteolytic degradation of specific autoantigens. Secondary necrosis may occur in vivo in autoimmune disorders associated with impaired clearance of apoptotic cells and serve as a source of modified forms of specific autoantigens that might stimulate autoantibody responses under proinflammatory conditions.

Amino Acid Chloromethyl Ketones↗
PubMed2001

Genetic counseling impacts decision for prophylactic surgery for patients perceived to be at high risk for breast cancer.

BACKGROUND: This study addresses the impact a comprehensive genetic counseling program had on women considering prophylactic mastectomy or oophorectomy. METHODS: Sixty patients underwent detailed family evaluation and risk was estimated. Recommendations were made regarding testing. Ramifications of testing were discussed in detail. RESULTS: Thirty-one women (37%) were considering prophylactic surgery believing themselves to be at high risk. Of these, 23 had testing recommended. Seven patients proceeded with prophylactic surgery based solely on high-risk assessment. Ten women were tested; five were positive. Three patients proceeded with prophylactic surgery despite a negative test. One decided against surgery despite a positive test. After counseling, prophylactic surgery was performed in just over half the initial candidates. CONCLUSIONS: Breast cancer risk estimation and genetic evaluation can be complex. Comprehensive genetic risk assessment programs can play a significant role in the management of patients considering prophylactic surgery for perceived high risk.

Adolescent↗
PubMed2001

Arylamine N-acetyltransferases - of mice, men and microorganisms.

Arylamine N-acetyltransferases (NATs) catalyse the transfer of an acetyl group from acetyl CoA to the terminal nitrogen of hydrazine and arylamine drugs and carcinogens. These enzymes are polymorphic and have an important place in the history of pharmacogenetics, being first identified as responsible for the polymorphic inactivation of the anti-tubercular drug isoniazid. NAT has recently been identified within Mycobacterium tuberculosis itself and is an important candidate for modulating the response of mycobacteria to isoniazid. The first three-dimensional structure of the unique NAT family shows the active-site cysteine to be aligned with conserved histidine and aspartate residues to form a catalytic triad, thus providing an activation mechanism for transfer of the acetyl group from acetyl CoA to cysteine. The unique fold could allow different members of the NAT family to play a variety of roles in endogenous and xenobiotic metabolism.

Alleles↗