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Biomedical subjects

J Dixon

Publications and source records attributed to J Dixon.

At least 91 records · Page 5Linked to original sources
PubMed1997

Clinical features in four patients with Angelman syndrome resulting from paternal uniparental disomy.

Angelman syndrome (AS) is a complex neurological disorder with different genetic aetiologies. It is not known whether the clinical features vary depending on the genetic mechanism. We report four patients with AS owing to uniparental disomy (UPD). There were two males and two females, with a mean age of 8 years (range 7 to 11 years). All patients had a happy disposition, hyperactive behaviour, and the characteristic facial phenotype of AS, but in three there was a normal head circumference, two had epilepsy, ataxic movements were mild in three, the mean age of onset of walking was 2.4 years, and there was some sign language in all four patients. Our cases add further weight to the previously reported impressions of a milder phenotype in cases of AS resulting from UPD than in deleted AS patients. Patients suspected of having AS, but who are considered atypical, warrant DNA testing.

Abnormalities, Multiple↗
PubMed1996

Genomic organization of the human heparan sulfate-N-deacetylase/N-sulfotransferase gene: exclusion from a causative role in the pathogenesis of Treacher Collins syndrome.

Heparan sulfate-N-deacetylase/N-sulfotransferase (HSST) catalyzes both the N-deacetylation and the N-sulfation of heparan sulfate. Previous studies have resulted in the isolation of the human HSST gene from within the Treacher Collins syndrome locus (TCOF1) critical region on 5q. In the present study, the genomic organization of the HSST gene has been elucidated, and the 14 exons identified have been tested for TCOF1-specific mutations. As a result of these studies, mutations within the coding sequence and adjacent splice junctions of HSST can be excluded from a causative role in the pathogenesis of Treacher Collins syndrome.

Amidohydrolases↗
PubMed1996

Molecular analysis of the Huntington's disease gene in New Zealand.

AIMS: To establish and validate a polymerase chain reaction (PCR)-based diagnostic test in New Zealand, which enables the number of CAG repeats present in the Huntington's disease (HD) gene to be determined with speed and accuracy. To develop procedures for reporting and counselling probands and families. METHODS: The analysis of the CAG repeat region in Huntington's disease and normal chromosomes involved PCR amplification of genomic DNA using either the incorporation of radioactive deoxynucleotides or fluorescent oligonucleotide primers. RESULTS: The molecular analysis of the CAG repeat sequence in the Huntington's disease gene of over 100 New Zealand individuals has been performed. Huntington's disease chromosomes contained 37-70 (median 44) repeats whereas normal chromosomes contained 9-27 (median 18) repeats. Six individuals from three families had an allele in the intermediate range (30-36 repeats). Instability of the CAG repeat upon transmission from generation to generation was also observed. A comparison of the results obtained using radioactive and fluorescent assays indicates that while both methods are reliable, the latter method is more rapid and allows for automation to be incorporated in the scoring of allele sizes. CONCLUSIONS: Our analysis of Huntington's disease alleles has shown a profile of CAG repeat lengths that is consistent with those reported internationally. In addition, reporting and counselling procedures have been established for presymptomatic testing of Huntington's disease in New Zealand.

DNA↗
PubMed1996

Effect of supplementation with selenium on whole blood glutathione peroxidase activities and on plasma and tissue selenium concentrations in lambs.

In recent years the selenium (Se) intake of the human population of the UK has shown a marked decline from 60 micrograms/d in 1978 to around 30 micrograms/d in 1990 owing largely to a significant reduction in the importation of North American wheat for bread-making flour. Other countries (Finland, for example) in similar situations have instituted fertilization programs in order to raise cereal Se concentrations and thus boost dietary intakes. An alternative approach would be to increase the Se concentration of carcass meat by supplementation of meat animals for a limited period prior to slaughter. A trial was set up with store lambs to evaluate this approach. Sixteen Scottish Blackface lambs were stratified according to live weight and then randomly allocated to one of four treatments: unsupplemented, or 3.5, 7, or 10.5 mg Se/head/wk. After 14 wk, the lambs were sacrificed and samples of shoulder and thigh muscle, liver, and kidney were obtained for analysis. All three treatments effected an increase in whole blood glutathione peroxidase (GSH-Px) and plasma Se concentrations over controls. Shoulder, thigh, and liver Se exhibited a dose-response relationship to treatment, but kidney Se concentrations were unaffected by treatment. Muscle and some organ meat Se concentrations can therefore be increased by supplementation and could contribute to increased human dietary intakes of the element.

Animal Feed↗
PubMed1996

Treacher Collins syndrome may result from insertions, deletions or splicing mutations, which introduce a termination codon into the gene.

Treacher Collins syndrome is an autosomal dominant disorder of craniofacial development the features of which include conductive hearing loss and cleft palate. Recently, the Treacher Collins syndrome gene (TCOF1) has been positionally cloned and a series of five mutations within the coding sequence of the gene identified. In the current investigation, seven exons of TCOF1 have been identified which has permitted the identification of additional mutations in the gene. The mutations that have been identified are three distinct deletions and an insertion, which cause a frameshift, and a missense mutation which inactivates a donor splice site with extension of transcription into the intron. To date, all 10 of the mutations which have been reported result in a premature termination codon and are unique to a given family. As these mutations are spread throughout the gene, these observations provide further support for the hypothesis that Treacher Collins syndrome results from haploinsufficiency, although a dominant negative effect cannot, at this stage, be excluded.

Exons↗
PubMed1996

Transcriptional map of the Treacher Collins candidate gene region.

Treacher Collins syndrome (TCOF1) is a dominant disorder of craniofacial development that has been linked previosuly to a region of chromosome 5q31.3-32. Identification of recombination events in affected individuals has reduced the candidate gene region to a 0.5-Mb area between the loci RPS14 (proximal) and ANX6 [distal]. A transcriptional map of this candidate gene region, generated by analysis of exon amplification clones, has identified the genomic location of four genes, heparan sulfate-N-sulfotransferase-N-deacetylase, glutathione peroxidase, as well as two novel, previously uncharacterized genes. Each of these genes, based on their location, must be considered candidates for TCOF1 locus.

Amidohydrolases↗
PubMed1996

Distribution of capsular types and antibiotic susceptibility of invasive Streptococcus pneumoniae isolated from aborigines in central Australia.

Streptococcus pneumoniae strains isolated from 203 episodes of invasive disease in central Australian Aborigines were studied. Capsular types from children aged 0 to 4 years (n = 89) belonged most commonly to types 14, 6B, 9V, 4, 18C, and 19F, which together accounted for 67% of the pediatric strains. In adults (n = 98), types 1, 7F, 3, 4, 12F, and 8 contributed 68% of the isolates. Of 114 pneumococci from patients 5 years and older, 102 (89.5%) were types represented in the 23-valent pneumococcal polysaccharide vaccine. The MICs of five antibiotics were determined for 201 strains by using the E-Test (AB Biodisk). No chloramphenicol or ceftriaxone resistance was found, but 46 strains (22.9%) showed diminished susceptibility to one or more of the drugs penicillin, erythromycin, and trimethoprim-sulfamethoxazole. Penicillin resistance occurred in 15.4% of all isolates tested but only within the intermediate range (0.1 to 1.0 microgram/ml). Resistance to trimethoprimsulfamethoxazole affected 13.9% of the pneumococci tested. All type 23F and most type 19F organisms were resistant to one or more antibiotics. Resistance was significantly more common in pediatric isolates than in those from adults (chi 2(1) = 14.1; P < 0.001).

Adolescent↗
PubMed1996

Clinical features in 27 patients with Angelman syndrome resulting from DNA deletion.

We report the clinical features in 27 Australasian patients with Angelman syndrome (AS), all with a DNA deletion involving chromosome 15(q11-13), spanning markers from D15S9 to D15S12, about 3 center dot 5 Mb of DNA. There were nine males and 18 females. All cases were sporadic. The mean age at last review (end of 1994) was 11 center dot 2 years (range 3 to 34 years). All patients were ataxic, severely retarded, and lacking recognisable speech. In all patients, head circumference (HC) at birth was normal but skewed in distribution, with 62 center dot 5% at the 10th centile. At last review HC was around the 50th centile in three patients (12 center dot 5%) while 15 had poor postnatal head growth. Short stature was not invariable, 5/26 (19%) were on or above the 50th centile. Hypotonia at birth was recorded in 15/24 (63%) and neonatal feeding difficulties were recorded in 20/26 (77%). Epilepsy was present in 26/27 (96%) with onset by the third year of life in 20 patients (83%). Improvement in epilepsy was reported in 11/16 patients (69%) with age. An abnormal EEG was reported in 25/25 patients. Hypopigmentation was present in 19/26 (73%). One patient had oculocutaneous albinism. Five patients could not walk independently. Of the remaining 22 who could walk, age of onset of walking ranged from 2 to 8 years. Disrupted sleep patterns were present in 18/21 patients (86%), with improvement in 9/12 patients (75%) over 10 years of age. The clinical features in this group of deletional AS patients were similar to previous reports, but these have not separated patients into subgroups based on DNA studies. In our group of deletional cases, 100% showed severe mental retardation, ataxic movements, absent language, abnormal EEG, happy disposition (noted in infancy in 95%), normal birth weight and head circumference at birth, and a large, wide mouth. These features occurred with a higher frequency than in AS patients as a whole. Our study also provided information on the evolution of the phenotype. The data can act as a benchmark for comparisons of AS resulting from other genetic mechanisms.

Adolescent↗
PubMed1995

What do we known about fundholding in general practice?

The general practice fundholding scheme was introduced four years ago. So far its impact has not been formally evaluated nationally, but review of published research shows some trends. Fundholding has curbed prescribing costs and given general practitioners greater power to lever improvements in hospital services--for example, reducing waiting times for hospital treatment--but fundholding practices may have received more money than non-fundholding practices. The impact of fundholding on transactions costs, equity, and quality of care (particularly for patients of non-fundholding general practitioners) is unknown. Research into costly reforms such as fundholding needs to be coordinated.

Community Participation↗
PubMed1995

Cloning of the human heparan sulfate-N-deacetylase/N-sulfotransferase gene from the Treacher Collins syndrome candidate region at 5q32-q33.1.

Treacher Collins syndrome is an autosomal dominant disorder of craniofacial development, the features of which include conductive hearing loss and cleft palate. Previous studies have shown that the Treacher Collins syndrome locus is flanked by D5S519 and SPARC, and a yeast artificial chromosome contig encompassing this "critical region" has been completed. In the current investigation a cosmid containing D5S519 has been used to screen a human placental cDNA library. This has resulted in the cloning of the human heparan sulfate-N-deacetylase/N-sulfotransferase gene. Two different mRNA species that have identical protein coding sequences but that differ in the size and sequence of the 3' untranslated regions (3' UTR) have been identified. The smaller species has a 3' UTR of 1035 bp, whereas that of the larger is 4878 bp.

Amidohydrolases↗
PubMed1995

Invasive pneumococcal disease in central Australia.

OBJECTIVES: To document the incidence, case fatality, clinical and demographic features of invasive pneumococcal disease in central Australia. DESIGN: Invasive isolates from the regional central laboratory were prospectively recorded over five years and case notes retrospectively reviewed. Population denominators were calculated from national Census data from 1986 and 1991. RESULTS: The population estimates for the region were 14,568 for Aboriginals and 28,680 for non-Aboriginals. There were 185 episodes of invasive pneumococcal disease over the five years, 162 (87.5%) in Aboriginals and 23 (12.5%), in non-Aboriginals. The incidence in Aboriginal children under two years of age was 2052.7 per 100,000 and for those 20-59 years was 178.2 per 100,000. The relative risk in Aboriginals compared with non-Aboriginals was 10.8 (95% CI, 5.6-20.7; P < 0.0001) for those aged 0-4 years and 20.4 (95% CI, 9.7-42.5; P < 0.0001) for those 15-59 years. Forty-one Aboriginal adults aged over 14 (62%) had at least one conventional risk factor for pneumococcal disease; alcohol abuse was present in 27 (41%). There were 13 Aboriginal deaths and the case fatality rose from 2% in those under four years to 40% for those over 59 years. CONCLUSIONS: Central Australian Aboriginals have the highest incidence of invasive pneumococcal disease reported. The rate for children under two years is 59 to 80 times the rates for children in the United States and Sweden. These data have implications for improving vaccine use, health service delivery and environmental health in Aboriginal communities.

Adolescent↗
PubMed1995

Renal amino acid transport in adults with oxidative phosphorylation diseases.

The clinical manifestations of mitochondrial DNA (mtDNA) mutations depend on a variety of factors including ratios of normal to abnormal mtDNA and tissue-specific differences in ATP production by oxidative phosphorylation (OXPHOS). In order to investigate the effects of OXPHOS defects on renal tubule function, we characterized sodium-coupled transport processes in six individuals with OXPHOS diseases. Pathogenic mtDNA mutations were identified in five of these individuals. Sodium coupled transport processes were evaluated by determining fractional excretions of amino acids, glucose, lactate, urate, and phosphate in patients and controls. Four of the six individuals had high fractional excretions of neutral amino acids, indicating abnormal renal tubule reabsorbtion of these amino acids. Abnormalities in fractional excretions of lactate, glucose, urate, and phosphate were less pronounced. These results demonstrate that sodium-coupled transport processes in the kidney are sensitive to OXPHOS impairment. When abnormalities in these processes are encountered, an OXPHOS disease should be included in the differential diagnosis.

Adenosine Triphosphate↗
PubMed1995

HIV risk-taking behaviour among injecting drug users currently, previously and never enrolled in methadone treatment.

This study compares the injecting and sexual risk-taking behaviour among injecting drug users (IDUs) currently, previously and never enrolled in methadone maintenance treatment (MMT). All subjects had injected during the 6 months prior to the day of interview. The current MMT group showed significantly lower injecting risk-taking behaviour subscale scores on the HIV Risk-taking Behaviour Scale (HRBS) of the Opiate Treatment Index than the previous MMT and non-MMT groups together. The current MMT group differed from the other two groups in the frequency of injecting and cleaning of injection equipment with bleach. There was no difference between the current MMT group and the other two groups combined in sexual risk-taking behaviour scores on the HRBS. There were no differences between the previous MMT and non-MMT groups in injecting and sexual risk-taking behaviour. HIV seroprevalence was low and there was no difference in seroprevalence between groups. Thus, IDUs currently enrolled in MMT are at reduced risk for HIV infection when compared with IDUs who have previously or never been enrolled in MMT. However, the absence of a difference between the current MMT and other two groups in frequency of sharing behaviours suggests the need for additional strategies among MMT clients to reduce needle-sharing. Possible strategies include the application of relapse prevention interventions and the availability of sterile injecting equipment in MMT clinics. Further research is needed to identify factors which increase attraction and retention of IDUs to MMT.

Acquired Immunodeficiency Syndrome↗