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N Williams

Publications and source records attributed to N Williams.

At least 127 records · Page 7Linked to original sources
PubMed1998

Subunit 9 of the mitochondrial ATP synthase of Trypanosoma brucei is nuclearly encoded and developmentally regulated.

We have previously shown that the mitochondrial ATP synthase is developmentally regulated through the life cycle of Trypanosoma brucei. The mechanism of this regulation is as yet unknown. We are currently examining regulation of expression of several key subunits of the ATP synthase to investigate this mechanism. In the work presented here, we have cloned, sequenced, and confirmed the identity of the ATPase subunit 9 homologue from T. brucei. The ATPase subunit 9 gene that we have identified from T. brucei has between 40 and 600% identity with subunit 9 from a variety of organisms. This gene possesses a putative mitochondrial import sequence at the N terminus of the encoded protein sequence. The protein expressed from this gene by in vitro transcription/translation comigrates with native protein isolated from inner mitochondrial membrane vesicles from T. brucei. We have shown that the cDNA identifies a copy of this gene in the nuclear genome, but does not identify a similar gene in kinetoplast DNA (kDNA) prepared from T. brucei. This gene does not show homology to any published sequence data from maxicircle DNA or edited maxicircle derived sequences. Steady state transcripts of a single size have been identified by Northern analysis and demonstrate significant developmental regulation through the T. brucei life cycle. Northern analysis and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) results show that the transcript is 10-14-fold higher in procyclic form than in early and late bloodstream forms.

Amino Acid Sequence↗
PubMed1998

Developmental regulation of two nuclear RNA binding proteins, p34 and p37, from Trypanosoma brucei.

We have previously reported the purification of two closely related nucleic acid binding proteins, p34 and p37, from Trypanosoma brucei and the cloning and sequencing of the two genes encoding these two proteins. The predicted primary structures of the two proteins are nearly identical with one major and several minor differences. Three sequence motifs have been identified in both proteins: an N-terminal alanine, proline, and lysine rich domain, one and a half internal consensus RNA binding domains, and a C-terminal KKDX repeat region. p34 and p37 bind preferentially to heterogeneous RNA as compared with other nucleic acids. Here, we report the developmental regulation of the expression of these two highly related proteins and their intracellular localization in T. brucei. The results indicate that these two RNA binding proteins are differently regulated through the Trypanosoma brucei life cycle. The steady state level of p34 transcript and protein are highest in the procyclic form. In bloodstream form, however, the p34 message is readily detectable, while the protein is not detectable. The p37 transcript level is nearly as high as that for p34 in procyclic form, while the p37 protein level is low. In bloodstream form p37 protein does correlate with the relative abundance of the steady state mRNA level. The two proteins have been localized to the nucleus by immunofluorescent confocal microscopy and subcellular fractionation.

Amino Acid Sequence↗
PubMed1998

A study of chromosome 4p markers and dopamine D5 receptor gene in schizophrenia and bipolar disorder.

There are several lines of evidence which suggest that chromosome 4p may contain a major susceptibility locus for the functional psychoses. We previously reported a family (family 50) with cases of schizophrenia and schizoaffective disorder which gave maximum lod scores of 1.96 and 1.84 respectively with the markers D4S403 and a microsatellite near to DRD5 (DRD5-M). More recently Blackwood and co-workers described a family segregating bipolar and unipolar affective disorders which gives a maximum lod score of 4.1 with the marker D4S394, which lies 10 cM from D4S403. They obtained a combined maximum lod of 3.3 in their total sample of 12 bipolar families and found significant evidence of heterogeneity (chi 2 = 18.8, df = 2, P = 0.00008). Here we report the results of a linkage study of chromosome 4p markers in a sample of 24 multiply affected families with schizophrenia and related disorders. We obtained an overall maximum lod of 1.12 with D4S403 under both dominant and recessive modes of transmission, with no statistical support for heterogeneity within our sample. Examination of family by family data shows that only family 50 appears to show linkage at this locus. However, a discrepancy exists since our study examined families fulfilling criteria for a linkage study of schizophrenia while Blackwood et al examined families included in a genetic linkage study of bipolar disorder. This may be explained by the clinical features displayed by members of family 50, which show that all the affected members have some affective symptoms. It is therefore possible that a broad phenotype including unipolar depression, bipolar disorder, schizoaffective disorder and schizophrenia when accompanied by significant affective symptoms can result from mutations within a gene in this region. The dopamine D5 receptor gene lies within the region identified by the linkage studies and is therefore a major candidate for the putative disease gene. In family 50 we have looked for mutations of DRD5 by sequence analysis of the coding region and single stranded conformational polymorphism (SSCP) analysis of the promoter. SSCP analysis of the coding and promoter regions have also been carried out in unrelated cases of DSM-IIIR schizophrenia. Finally association studies of the (TC)n repeat in the promoter and schizophrenia, and DRD5-M and bipolar disorder were performed. These studies provided no further evidence supporting the possibility that mutations in DRD5 give rise to the linkage findings or are acting as susceptibility loci in schizophrenia or bipolar disorder.

Base Sequence↗
PubMed1998

Physiological and functional outcome following ultra-low anterior resection with colon pouch-anal anastomosis.

BACKGROUND: Low rectal cancer is usually managed by ultra-low anterior resection (ULAR) with total mesorectal excision and straight coloanal anastomosis. However, following this procedure patients often suffer from frequency, urgency of bowel action and, occasionally, faecal incontinence. To overcome such problems, a colon pouch may be fashioned and a subsequent colon pouch-anal anastomosis performed. The physiological and functional outcome following the use of a colon pouch are appraised. METHODS: All relevant papers identified from a Medline search and papers from cross-referencing were reviewed. RESULTS AND CONCLUSION: Creation of a colon pouch following ULAR results in reduced bowel frequency, and a lower incidence of urgency and faecal incontinence. Although there is a slightly increased incidence of evacuatory disorder and need for enemas or suppositories, this appears to be a minor problem which may possibly be overcome by using a smaller colon pouch. Compared with straight coloanal anastomosis following ULAR, the creation of a colon pouch produced a superior functional outcome.

Anal Canal↗
PubMed1998

A simple method for analyzing microsatellite allele image patterns generated from DNA pools and its application to allelic association studies.

Allelic association studies provide the most powerful method for locating genes of small effect contributing to complex diseases and traits. However, in outbred populations, allelic association is usually maintained only over distances of <=1 cM. Therefore, systematic searches over large regions are costly. Here we present a method involving DNA pooling that can be used as a rapid preliminary screen for allelic association with the most common class of polymorphic markers, single-sequence repeats. Patient and control samples are pooled separately, and markers are typed in the two pools. By use of primers with fluorescent 5' ends, PCR products can be analyzed on an automated sequencing apparatus. Allele image patterns (AIPs) produced for the two groups are overlaid and differences in pattern area between pools computed. From this, a DeltaAIP statistic is calculated from the difference in areas between the two AIPs expressed as a fraction of the total shared and nonshared area. AIPs of a range of different-sized pools were generated by computer simulation for markers with a range of allele sizes and frequencies. DeltaAIPs from pools and chi2 values for individual genotypings were compared, with both simulated and real data from microsatellite markers. The results demonstrated a high correlation between DeltaAIP and chi2 values. DeltaAIP analysis of real microsatellite data indicated the feasibility of using this method in systematic searches for allelic association and generated a small number of false positives but few false negatives. We conclude that DeltaAIP analysis of DNA pools can be used effectively and efficiently as a rapid screen for allelic association in case-control studies.

Alleles↗
PubMed1998

Nasal septal ulceration and perforation in jiggers.

The paper describes two cases of occupational ill-health in individuals working as jiggers in the chromium electroplating industry. Much has been written about the effects of chromic acid on the platers who may work directly over the plating baths, but a literature search failed to identify any reports of ill-health in those who work alongside platers preparing the items to be placed into the baths. One case of nasal ulceration and one of nasal septal perforation are described. Reference is made to the role of the 'responsible person' in health surveillance for such workers to allow early identification of occupationally acquired ill-health and prevention of further cases.

Adolescent↗
PubMed1998

Perforation rate relates to delayed presentation in childhood acute appendicitis.

To determine if perforation rate is a function of delayed diagnosis or delayed presentation in childhood acute appendicitis we performed a retrospective casenote review of 101 consecutive children undergoing emergency appendicectomy over a 12-month period. The perforation rate was 7% in those children presenting with symptoms of 1 day or less and was significantly greater (33%, Chi 2 = 9.45, P < 0.01) in those who had had symptoms for more than 1 day at presentation. There was no difference in in-hospital delay between the groups. A high perforation rate was found to be a feature of delayed presentation.

Acute Disease↗