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N Williams

Publications and source records attributed to N Williams.

At least 73 records · Page 4Linked to original sources
PubMed2001

Cloning and characterization of the subunits comprising the catalytic core of the Trypanosoma brucei mitochondrial ATP synthase.

The Trypanosoma brucei mitochondrial F(1)-ATPase has been previously isolated and characterized. It is composed of five subunits of molecular weights 55000, 42000, 32000, 22000, and 17000 [1]. We have identified the alpha and beta subunits of the T. brucei F(1)-ATPase by N-terminal sequence determination together with analysis of cDNA and genomic clones. The genes for both subunits are homologous to the same subunits from other organisms. They contain the Walker A and B boxes of homology and a putative mitochondrial import sequence. The isolated T. brucei alpha subunit is unusually small at 42 kDa. The alpha cDNA clone encodes a protein of predicted size 59 kDa with a mitochondrial import presequence at the N-terminus. The predicted size was confirmed by expression of a 59 kDa protein from the cDNA clone in vitro. These results suggest that the alpha subunit may have an unusually large mitochondrial presequence of 159 amino acids. In contrast, the estimated size of the native beta subunit (55 kDa) correlates well with the size predicted from the cDNA clone, 57 kDa, from which a 21 amino acid presequence has been removed in vivo. The size of the beta subunit was confirmed by expression in an in vitro and an Escherichia coli expression system. The purified recombinant beta subunit, like the native F(1)-ATPase, can be labeled by the photoaffinity nucleotide analogue 8-azido ATP. Binding of the 8-azido ATP probe is best competed by the natural substrate ATP, and is significantly reduced by pretreatment with the inhibitor 7-chloro-4-nitrobenzo-2-oxa-1,3-diazide as has been shown with beta subunits of other organisms. The differential binding of this photoaffinity analogue was used to resolve the identities of the alpha and beta subunits of the ATP synthase from T. brucei. These results are in contrast to results previously obtained for a related trypanosomatid Crithidia fasciculata.

Amino Acid Sequence↗
PubMed2001

Localization of the gene for distal hereditary motor neuronopathy VII (dHMN-VII) to chromosome 2q14.

Distal hereditary motor neuronopathy type VII (dHMN-VII) is an autosomal dominant disorder characterized by distal muscular atrophy and vocal cord paralysis. We performed a genomewide linkage search in a large Welsh pedigree with dHMN-VII and established linkage to chromosome 2q14. Analyses of a second family with dHMN-VII confirmed the location of the gene and provided evidence for a founder mutation segregating in both pedigrees. The maximum three-point LOD score in the combined pedigree was 7.49 at D2S274. Expansion of a polyalanine tract in Engrailed-1, a transcription factor strongly expressed in the spinal cord, was excluded as the cause of dHMN-VII.

Chromosome Mapping↗
PubMed2001

Ancient chemistry fuels new biology.

An enormous new greenhouse project in southern Britain aims to heighten awareness of the human relationship with plants and the growing potential of plant-derived compounds to find new uses, reports Nigel Williams

Biological Factors↗
PubMed2001

Mendel's demon.

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Genetics↗
PubMed2001

Lessons from the human embryo debate.

Britain has given the green light for research on stem cells derived from human embryos. Nigel Williams reports on the discussion ahead of this controversial decision.

Embryo, Mammalian↗
PubMed2001

The Trypanosoma brucei mitochondrial ATP synthase is developmentally regulated at the level of transcript stability.

The mitochondrial ATP synthase is developmentally regulated throughout the life cycle of the Trypanosoma brucei. The alpha and beta subunits of the F(1) moiety, and subunit 9 of the F(0) moiety of the T. brucei ATP synthase have been previously cloned and characterized. Here we have determined the chromosomal localization and developmental regulation of these three key subunits of the complex. Southern blot analysis indicates that all three of these genes are present as single copies in the T. brucei genome. Pulsed field gel analysis demonstrates that these genes are encoded in different chromosomes, and are thus not part of the same gene cluster. A comparison between the protein and steady state transcript levels for these subunits suggests that regulation of expression occurs predominantly posttranscriptionally. Comparison of mRNA stability for procyclic and bloodstream forms shows that the half life of the three transcripts is much shorter in bloodstream forms. The differences in transcript stability in the procyclic form for subunit 9 is greater than that for alpha and beta subunits, while the differences at the protein levels are comparable. These results suggest that there may be further posttranscriptional regulation of subunit 9.

Animals↗
PubMed2001

Increased acid-sensing ion channel ASIC-3 in inflamed human intestine.

OBJECTIVES: Acid-sensing ion channels (ASICs) are expressed by rat sensory neurons and may mediate pain associated with tissue acidosis after inflammation or injury. Our aim was to examine the molecular forms and localization of ASICs in human intestine and dorsal root ganglia using immunochemical techniques, and to measure the effects of inflammation and injury. DESIGN AND METHODS: Inflamed Crohn's disease intestine and injured human dorsal root ganglia, with appropriate controls, were studied by Western blotting and immunohistochemistry, using specific affinity-purified ASIC antibodies. RESULTS: In the Western blot, there was a significant three-fold increase in the mean relative optical density of the ASIC-3 55-kDa band (but not ASIC-1 or ASIC-2) in full-thickness inflamed intestine, as well as in separated muscle and mucosal layers. There was a corresponding trend for an increased immunoreactive density and increased number of ASIC-3-positive neurons in the myenteric and sub-mucous plexus of inflamed intestine. In dorsal root ganglia, immunoreactivity for all ASICs was restricted to a sub-population (about 50%) of small-diameter (nociceptor) sensory neurons, and was generally less intense after injury. CONCLUSIONS: Increased ASIC-3 in inflamed intestine suggests a role in pain or dysmotility, for which ASICs represent new therapeutic targets.

Acid Sensing Ion Channels↗
PubMed2001

Sensory defensiveness: a theory of its effect on breastfeeding.

This article describes one type of sensory integrative disorder: sensory defensiveness. An examination of the possible relationship of this disorder to an infant's difficulties with breastfeeding is conducted. A family case study is detailed, followed by treatments implemented by the authors. Possible long-term sequelae, as well as the need for more interdisciplinary research, are discussed.

Adult↗
PubMed2001

Minimally invasive parathyroidectomy without intraoperative localization.

Minimally invasive parathyroidectomy (MIP) is gaining popularity as an alternative to traditional bilateral exploration for patients with primary hyperparathyroidism. The success of MIP relies on the ability of preoperative and intraoperative localization studies to guide a directed exploration for resection of a diseased gland. We hypothesize that excellent results can be achieved with MIP when only technetium-99m sestamibi (MIBI) is used for localization. We conducted a prospective analysis of all patients presenting with a biochemical diagnosis of primary hyperparathyroidism between January 1997 and November 2000. Patients meeting inclusion criteria were given a choice of MIP and directed exploration versus traditional bilateral exploration. Fifty patients chose MIP. Three patients who chose MIP had a negative MIBI, which left 47 patients in the primary study group. The MIBI correctly identified a parathyroid adenoma in 42 patients (89.3%). In two other patients MIBI was inaccurate; however, directed exploration was successfully converted to a bilateral exploration. Overall 44 of 47 (93.6%) patients in the study group were rendered normocalcemic after the initial operation. Three patients experienced persistent hypercalcemia and subsequently underwent successful bilateral exploration. Including those patients choosing a bilateral exploration, a total of 59 positive MIBI scans were evaluated. There were 54 true positives (positive predictive value 91.5%), and if all patients had chosen a MIP 94.9 per cent would have been successfully treated at the initial operation. Mean operative time for MIP was 54.6 minutes, and in 32 patients (68.1%) MIP was performed with local anesthesia and sedation. Twenty-six patients (55.3%) were discharged the same day of the procedure. There were no significant complications in any group analyzed. We conclude that MIP can be successfully performed on the basis of a positive MIBI scan. The present study highlighting many of the advantages of MIP questions the necessity of additional adjuncts such as intraoperative parathyroid hormone measurement and gamma-probe localization.

Adenoma↗
PubMed2001

Outbreak of Salmonella indiana associated with egg mayonnaise sandwiches at an acute NHS hospital.

An outbreak of Salmonella indiana infection in December 2000 affected 17 staff, relatives and patients at an acute NHS Hospital in Swansea. Epidemiological investigation identified egg mayonnaise sandwiches as the vehicle of infection. It was not possible to definitively determine the source of the infection or how the prepared sandwiches became contaminated. The most likely explanation was a pasteurisation failure of a batch of the egg roll used to make these sandwiches. Sandwiches are the most frequently identified vehicle of infection in foodborne outbreaks of salmonella infection in hospitals in England and Wales. The process of sandwich preparation has inherent risks because it involves considerable handling of food, which is consumed without further cooking. Care is required in all stages of preparation including the sourcing of materials used to produce the sandwiches. NHS Trusts should review their Hazard Analysis Critical Control Point plans for sandwich production.

Case-Control Studies↗
PubMed2000

Brain story

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Journal Article↗
PubMed2000

Family-based association mapping provides evidence for a gene for reading disability on chromosome 15q.

Family-based association mapping was used to follow up reports of linkage between reading disability (RD) and a genomic region on chromosome 15q. Using a two-stage approach, we ascertained 101 (stage 1) and 77 (stage 2) parent-proband trios, in which RD was characterized rigorously. In stage 1, a set of eight microsatellite markers spanning the region of putative linkage was used and a highly significant association was detected between RD and a three-marker haplotype (D15S994/D15S214/D15S146: P and empirical P < 0.001). A significant association with the same three-marker haplotype was also observed in the second-stage sample (P = 0.009, empirical P = 0.006). Our data therefore provide strong evidence for one or more genes contributing to RD being located in the vicinity of the region including D15S146 and D15S994. In addition, our results provide support for association analysis being a useful method to map susceptibility loci for complex disorders.

Chromosome Mapping↗