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E Reid

Publications and source records attributed to E Reid.

At least 37 records · Page 2Linked to original sources
PubMed1999

Autosomal dominant spastic paraplegia: refined SPG8 locus and additional genetic heterogeneity.

OBJECTIVE: To map the gene responsible for autosomal dominant pure hereditary spastic paraplegia (ADPHSP) in a large affected family. BACKGROUND: Autosomal dominant pure hereditary spastic paraplegia (ADPHSP) is genetically heterogeneous, and loci have been mapped at chromosomes 2p (SPG4), 14q (SPG3), 15q (SPG6), and recently, in a single family, at chromosome 8q24 (SPG8). METHODS: The authors carried out a genomewide linkage screen on a large family with ADPHSP, for which linkage to the chromosome 2, 14, and 15 loci was excluded. RESULTS: Analysis of markers on chromosome 8q24 gave a peak two-point lod score of 4.49 at marker D8S1799. Analysis of recombination events in this family and in the previously published SPG8-linked family narrowed the SPG8 locus from 6.2 cM to a 3.4-cM region between markers D8S1804 and D8S1179. In another four families, linkage to all four known ADPHSP loci was excluded. The SPG8-linked family had a significantly older mean age at onset of symptoms and had significantly more wheelchair-using patients than the four linkage-excluded families. CONCLUSIONS: These results contain the presence of an autosomal dominant pure hereditary spastic paraplegia (ADPHSP) locus at chromosome 8q24 and strongly suggest that there are at least five ADPHSP loci. The data provide additional evidence for locus-phenotype correlations in ADPHSP.

Adult↗
PubMed1999

The hereditary spastic paraplegias.

The hereditary spastic paraplegias are a complex group of neurodegenerative conditions which are characterised by slowly progressive lower limb spasticity. This article describes the main clinical features of pure and complicated hereditary spastic paraplegias and summarises recent advances in our understanding of the molecular genetics of these conditions.

Diagnosis, Differential↗
PubMed1999

A new locus for autosomal dominant "pure" hereditary spastic paraplegia mapping to chromosome 12q13, and evidence for further genetic heterogeneity.

Autosomal dominant pure hereditary spastic paraplegia (ADPHSP) is clinically characterized by slowly progressive lower-limb spasticity. The condition is genetically heterogeneous, and loci have been mapped at chromosomes 2p, 8q, 14q, and 15q. We have performed a genomewide linkage screen on a large family with ADPHSP, in which linkage to all four previously known loci was excluded. Analysis of markers on chromosome 12q gave a peak pairwise LOD score of 3.61 at D12S1691, allowing us to assign a new locus for ADPHSP (a locus that we have designated "SPG10") to this region. Haplotype construction and analysis of recombination events narrowed the SPG10 locus to a 9.2-cM region between markers D12S368 and D12S83. In addition, our data strongly suggest that there are at least six ADPHSP loci, since we describe a further family in which linkage to all five known ADPHSP loci has been excluded.

Adolescent↗
PubMed1999

Locus-phenotype correlations in autosomal dominant pure hereditary spastic paraplegia. A clinical and molecular genetic study of 28 United Kingdom families.

This study aimed to describe the clinical phenotype of a large collection of families with autosomal dominant pure hereditary spastic paraplegia (ADPHSP), to examine the relative frequency of each of the three known ADPHSP genes within this population, to assess locus-phenotype correlation in ADPHSP and to ascertain whether there are clinical subgroups within genetically defined populations of ADPHSP families. We examined 306 family members, 144 affected, from 28 families with ADPHSP. Linkage analysis at the three known ADPHSP loci allowed us to categorize the families into three groups: (i) those families showing linkage to the chromosome 2 ADPHSP locus (seven families); (ii) those in which linkage to all known loci was excluded (five families); and (iii) those in which linkage results were inconclusive. There was a correlation between linkage group and clinical features, with chromosome 2-linked families having a later age at onset of symptoms (P = 0.001) and later age before commencing walking stick use (P = 0.007) than those families in which linkage to all known ADPHSP loci was excluded. There were no clinical differences between the families showing linkage to the chromosome 2 locus, but there were clinical differences between the families in which linkage to all of the known loci had been excluded (P < 0.0001). We conclude that the chromosome 2 ADPHSP gene is a frequent cause of ADPHSP in UK families, that the responsible gene has not yet been mapped in a significant proportion of families and that certain clinical features of ADPHSP, including age at onset, are at least in part determined by genetic locus.

Adolescent↗
PubMed1999

Activated protein C resistance and the FV:R506Q mutation in a random population sample--associations with cardiovascular risk factors and coagulation variables.

Activated protein C (APC) resistance, defined as a low APC ratio, is associated with the factor V mutation R506Q (factor V Leiden). APC ratio may also be influenced by other clinical and coagulation variables, which we studied in 460 men and 495 women aged 25-74 years, from a random population sample (Glasgow MONICA Survey). APC ratio correlated positively with APTT; and inversely with factor VIIIc, factor IXc, antithrombin activity, prothrombin F1+2 fragment, and thrombin-antithrombin complexes; but not with other coagulation variables. APC ratio decreased with age, but APTT did not. APC ratio and APTT were significantly lower in women versus men, and were significantly lower in users of oral contraceptives or hormone replacement therapy. The FV:R506Q mutation (prevalence 2.5%) was associated with lower APC ratio and protein C and S activities and with higher factor VIIIc levels; but not with increases in F1+2 fragment or thrombin-antithrombin complexes. APC ratio correlated inversely with total cholesterol and diastolic blood pressure; and in women with triglycerides, systolic blood pressure, and body mass index. Obesity was associated with a significantly lower APC ratio. In contrast, smoking markers correlated positively with APC ratio in men. These associations of APC ratio may be relevant to the increased risks of venous thrombosis with age, female sex, oestrogen use, obesity and high factor VIIIc levels. The association of APC resistance with elevated plasma levels of coagulation markers suggests that this phenotype represents an in vivo hypercoagulable state.

Activated Protein C Resistance↗
PubMed1998

The CcmE protein from Escherichia coli is a haem-binding protein.

We previously reported that a 17.5-kDa haem-binding polypeptide accumulates in Escherichia coli K-12 mutants defective in an essential gene for cytochrome c assembly, ccmF, and speculated that this polypeptide is either CcmE or CcmG. The haem-containing polypeptide, which is associated with the cytoplasmic membrane, has now been identified by N-terminal sequencing to be CcmE. The haem-dependent peroxidase activity of CcmE is clearly visible not only in a ccmF mutant, but also in ccmG and ccmH mutants, implying that CcmE functions either before or in the same step as CcmF, CcmG and CcmH in cytochrome c maturation. A trxA mutant, like the dipZ mutant, was unable to assemble c-type cytochromes or catalyse formate-dependent nitrite reduction: both activities were restored in the trxA and dipZ, but not ccmG, mutants by the reducing agent, 2-mercaptoethanesulphonic acid. Our data suggest that haem transferred across the cytoplasmic membrane by the CcmABCD complex becomes associated with CcmE, possibly by a labile covalent bond, before it is transferred to the cytochrome c apoproteins by the periplasmic haem lyase encoded by ccmF and ccmH. We further propose that CcmG is essential to reduce the disulphide bonds formed in cytochrome c apoproteins by DsbA, before haem is attached by the haem lyase. Electrons for disulphide bond reduction are supplied from thioredoxin in the cytoplasm via DipZ in the membrane, but can be replaced by the chemical reductant, 2-mercaptoethanesulphonic acid. According to this model, CcmG is the last protein in the reducing pathway which interacts stereospecifically with the apoprotein.

Bacterial Outer Membrane Proteins↗
PubMed1998

Transcriptional control and essential roles of the Escherichia coli ccm gene products in formate-dependent nitrite reduction and cytochrome c synthesis.

The eight ccm genes located at minute 47 on the Escherichia coli chromosome, in the order ccmABCDEFGH, encode homologues of proteins which are essential for cytochrome c assembly in other bacteria. The ccm genes are immediately downstream from the napFDAGHBC genes encoding a periplasmic nitrate reductase. CcmH was previously shown to be essential for cytochrome c assembly. Deletion analysis and a two-plasmid strategy have now been used to demonstrate that CcmA, B, D, E, F and G are also essential for cytochrome c assembly, and hence for cytochrome-c-dependent nitrite reduction. The ccm genes are transcribed from a ccmA promoter located within the adjacent gene, napC, which is the structural gene for a 24 kDa membrane-bound c-type cytochrome, NapC. Transcription from this ccmA promoter is induced approximately 5-fold during anaerobic growth, independently of a functional Fnr protein: it is also not regulated by the ArcB-ArcA two-component regulatory system. The ccmA promoter is an example of the 'extended -10 sequence' group of promoters with a TGX motif immediately upstream of the -10 sequence. Mutagenesis of the TG motif to TC, CT or CC resulted in loss of about 50% of the promoter activity. A weak second promoter is suggested to permit transcription of the downstream ccmEFGH genes in the absence of transcription readthrough from the upstream napF and ccmA promoters. The results are consistent with, but do not prove, the current view that CcmA, B, C and D are part of an essential haem transport mechanism, that CcmE, F and H are required for covalent haem attachment to cysteine-histidine motifs in cytochrome c apoproteins in the periplasm, and that CcmG is required for the reduction of cysteine residues on apocytochromes c in preparation for haem ligation.

Anaerobiosis↗
PubMed1998

Autosomal dominant juvenile recurrent parotitis.

Juvenile recurrent parotitis is a common cause of inflammatory salivary gland swelling in children. A variety of aetiological factors has been proposed for the condition. Here we present a family where four members had juvenile recurrent parotitis and where two other family members may have had an atypical form of the condition. The segregation pattern in the family is consistent with autosomal dominant inheritance with incomplete penetrance and this suggests that, at least in some cases, genetic factors may be implicated in juvenile recurrent parotitis.

Child↗
PubMed1996

Familial Wolf-Hirschhorn syndrome resulting from a cryptic translocation: a clinical and molecular study.

We present three cousins who have normal karyotypes, despite having clinical features of Wolf-Hirschhorn syndrome. Fluorescence in situ hybridisation techniques confirmed that all three relatives were monosomic for the distal short arm of chromosome 4 and that a cryptic translocation involving chromosomes 4 and 11 was segregating within the family. Segregation analysis indicated that the risk of an affected child being born to a parent carrying the translocation was 15%. Molecular analysis showed that loci D4S111 and D4S115 were not deleted in the proband, thus excluding these loci from the "Wolf-Hirschhorn critical region". Surprisingly, DNA studies also suggested that the translocation breakpoint on chromosome 4 was within the region of a preexisting paracentric inversion.

Abnormalities, Multiple↗
PubMed1996

Familial hemiplegic migraine in the west of Scotland: a clinical and genetic study of seven families.

OBJECTIVES: Clinical and genetic characterisation of families in the west of Scotland with familial hemiplegic migraine. METHODS: Families with familial hemiplegic migraine were identified via probands attending the regional paediatric neurology and child development centre. All available family members were assessed clinically and genetic linkage studies for the known familial hemiplegic migraine gene locus on chromosome 19 were carried out on three families. RESULTS: Seven unrelated kindreds with familial hemiplegic migraine were identified. Clinical information was obtained on 138 family members, 27 of whom fulfilled the International Headache Society criteria for familial hemiplegic migraine. Whereas the severity, duration, frequency, and temporal progression of acute hemiplegic migrainous attacks showed pronounced variability within and between families, and even in the same individual over time, no true clinical heterogeneity of the condition was apparent. Genetic linkage analysis gave results consistent with linkage to the familial hemiplegic migraine gene locus on chromosome 19p in one family. In the other two families, evidence against linkage was obtained. There was no significant clinical difference between these three families. CONCLUSIONS: This study provides characterisation of the clinical features of familial hemiplegic migraine in a British population. Significant variability was found in the frequency and character of migraine attacks within and between families, and no true clinical heterogeneity was identified. On the other hand, further evidence for genetic heterogeneity of the condition was found.

Adolescent↗
PubMed1994

Approaching the HIV epidemic: the community's response.

The HIV epidemic comes to people's attention through the language of its texts and its spokespersons. The way it is brought to people's attention will be the critical determinant of how they will respond to it. Currently, the discourse is based on metaphors of epicentres of spread identified as core transmitter groups. These are metaphors of distancing which encourage blame and denial. There are, however, within affected communities, new discourses emerging of inclusion, empowerment and processes and of the complexity of the reality of the epidemic. These discourses are associated with a new way of responding to the epidemic described here as one of community mobilization.

Attitude to Health↗
PubMed1994

Static respiratory compliance in the newborn. I: A clinical and prognostic index for mechanically ventilated infants.

Accurate measures of the severity of respiratory disease are important, both clinically and epidemiologically. The apparent prognostic value of static respiratory system compliance (Crs) on the first day and mean appropriate fractional inspired oxygen (FIO2) in the first 12 hours of life were compared in 48 infants who received mechanical ventilation in a regional neonatal unit. Their median (range) gestation was 30 (25-41) weeks and they were representative of all 140 newborn infants born to residents of a geographically defined area who received mechanical ventilation over a 30 month period. Using the best cut off value (< or = 0.6 ml/cm H2O/m corrected for body length), static Crs predicted hospital death with 98% accuracy, 80% sensitivity, and 100% specificity. Using the best cut off value (> 0.60), mean FIO2 in the first 12 hours predicted hospital death with 81% accuracy, 80% sensitivity, and 81% specificity. Static Crs appeared to be a more accurate measure of respiratory function and disease severity than mean FIO2, perhaps because static Crs is less dependent on ventilator management than routine indices based on blood gases. Static Crs now merits wider evaluation, both as an aid to routine clinical management and as a prognostic index in comparative studies.

Humans↗
PubMed1992

Maturation of functional antibody affinity in animals immunised with synthetic foot-and-mouth disease virus.

A good correlation exists between specific neutralising antibody titre and protection against challenge with foot-and-mouth disease virus (FMDV) in infected or virus-vaccinated cattle, but not in the case of animals immunised with synthetic FMDV peptides. Therefore, mechanisms other than simple neutralisation are likely to be important in vivo. Antibody affinity may influence the protective capacity of sera from immunised animals and experiments were carried out to measure the functional affinity for synthetic FMDV peptide of sera from guinea pigs and cattle given various synthetic vaccines. In guinea pigs given a single dose of synthetic vaccine, antibody affinity increased with time after immunisation. In cattle, however, administration of a second dose of peptide 21 days after the first markedly retarded the process of affinity maturation. For guinea pig sera of equivalent neutralising activity, those of higher functional affinity had higher protective indices than those of lower functional affinity. Knowledge of the importance of antibody affinity in protection against FMD is important for an improved understanding of the mechanisms of protection and for the design of novel vaccines.

Adjuvants, Immunologic↗