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Biomedical subjects

N Williams

Publications and source records attributed to N Williams.

At least 91 records · Page 5Linked to original sources
PubMed2000

Observation of a hybrid spin resonance

A new type of spin depolarization resonance has been observed at the Brookhaven Alternating Gradient Synchrotron (AGS). This spin resonance is identified as a strong closed-orbit sideband around the dominant intrinsic spin resonance. The strength of the resonance was proportional to the 9th harmonic component of the horizontal closed orbit and proportional to the vertical betatron oscillation amplitude. This "hybrid" spin resonance cannot be overcome by the partial snake at the AGS, but it can be corrected by the harmonic orbit correctors.

Journal Article↗
PubMed2000

Cheap, accurate and rapid allele frequency estimation of single nucleotide polymorphisms by primer extension and DHPLC in DNA pools.

At present, the cost of genotyping single nucleotide polymorphisms (SNPs) in large numbers of subjects poses a formidable problem for molecular genetic approaches to complex diseases. We have tested the possibility of using primer extension and denaturing high performance liquid chromatography to estimate allele frequencies of SNPs in pooled DNA samples. Our data show that this method should allow the accurate estimation of absolute allele frequencies in pooled samples of DNA and also of the difference in allele frequency between different pooled DNA samples. This technique therefore offers an efficient and cheap method for genotyping SNPs in large case-control and family-based association samples.

Alleles↗
PubMed2000

Comparative sequencing of the proneurotensin gene and association studies in schizophrenia.

Neurotensin (NT) is an endogenous tridecapetide1 cleaved from a precursor proneurotensin/ proneuromedin protein. NT localises within dopaminergic neurones in the mesocortical, mesolimbic and nigrostriatal systems1-3 and it is now clear that NT can selectively modulate dopaminergic neurotransmission.2-9 These anatomical and functional connections have led to the hypothesis that NT dysfunction might contribute to the pathogenesis of neuropsychiatric disorders in which disordered dopaminergic neurotransmission is suspected, particularly schizophrenia.3 The latter hypothesis has been supported circumstantially by the observation that central administration of NT produces effects similar to those produced by the peripheral administration of atypical antipsychotics,10,11 and more directly by studies showing levels of NT in cerebral spinal fluid (CSF) is lower in schizophrenics than in controls.12,13 To allow such hypotheses to be tested, we used denaturing high performance liquid chromatography (DHPLC)14 to identify three sequence variants in the neurotensin gene (NTS) that might alter NT structure or expression. However, using a case-control study design and a novel genotyping system based upon a primer extension protocol and HPLC detection,15 we found no evidence to support the hypothesis that variation in the proneurotensin gene contributes to susceptibility to schizophrenia.

Alleles↗
PubMed2000

The high affinity neurotensin receptor gene (NTSR1): comparative sequencing and association studies in schizophrenia.

Neurotensin and its high affinity receptor (NTSR1) localise within dopaminergic neurones in the mesocortical, mesolimbic and nigrostriatal systems and it is now clear that neurotensin can selectively modulate dopaminergic neurotransmission. This has led to the hypothesis that altered neurotensin function contributes to the pathogenesis of schizophrenia and other psychoses. This hypothesis has been supported circumstantially by a number of lines of evidence. (1) Central administration of neurotensin produces effects similar to those produced by the peripheral administration of atypical antipsychotics. (2) Observations of low levels of neurotensin in the CSF of schizophrenics. (3) Reduced numbers of neurotensin receptors in the brains of schizophrenics. Given the above link between neurotensin and dopamine, and the evidence implicating altered neurotensin function in psychosis, we have postulated that DNA sequence variation in neurotensin or its receptors might be associated with schizophrenia. In keeping with this hypothesis, an association has recently been reported between schizophrenia and the gene encoding the neurotensin high affinity receptor (NTSR1). However, caution is required because the associated marker, a tetranucleotide repeat, is located 3 kb away from the 3' end of the gene and there is no evidence that it is functional. Therefore, as a follow-up to our earlier work on neurotensin, we have now sought to test the hypothesis that DNA sequence variants that alter the structure or expression of the NTSR1 gene (VAPSEs) are associated with schizophrenia. However, while we found 14 novel sequence variants in 28 probands with psychosis, none resulted in an amino acid change, and neither direct nor indirect association studies suggested these are involved in susceptibility to schizophrenia.

Brain Chemistry↗
PubMed2000

Association analysis of the proneurotensin gene and bipolar disorder.

Neurotensin (NT) localizes within dopaminergic neurones in the mesocortical, mesolimbic and nigrostriatal systems, and it is now clear that NT can selectively modulate dopaminergic neurotransmission. It has therefore been proposed that altered NT function might contribute to the pathogenesis of neuropsychiatric disorders in which disordered dopaminergic neurotransmission is suspected. We have previously screened the gene encoding NT in a sample of schizophrenic and bipolar subjects, and identified three sequence variants. These have now been tested for association with bipolar disorder using a case-control sample of unrelated bipolar subjects and matched controls. No evidence for association was found, and our data therefore suggest that sequence variation in this gene does not make an important contribution to susceptibility to bipolar disorder.

Adult↗
PubMed2000

Schwannoma of the chorda tympani nerve.

We report a case of schwannoma of the chorda tympani. This is a very rare benign tumour and only five other cases have been found in the literature. This is the first case to mimic a cholesteatoma presenting as a pearly tumour in the postero-superior segment of the drum with aural discharge and conductive deafness. Diagnosis is usually by biopsy and treatment is surgical with preservation of facial and auditory function. A summary of the other presentations of this tumour together with a review of the histopathology of the disease is presented.

Cholesteatoma↗
PubMed2000

Pooled genotyping of microsatellite markers in parent-offspring trios.

We studied the extent to which genotyping of simple sequence repeat polymorphisms (SSRs) in pooled DNA samples can be used to predict differences in allele frequencies between parents and their affected offspring. We also developed a simple method of correction for the effects of stutter and differential amplification on the analysis of SSRs in pooled DNA samples based on widely available software. We genotyped individually eight polymorphic microsatellite markers in 110 parent-offspring trios affected with bipolar affective disorder (BP). Analysis of pooled DNA samples predicted very accurately the differences in individual allele frequency distributions between children and their parents. The mean error was <1% (range 0%-3.2%) when marker-specific corrections for stutter and differential amplification were performed. We show that if an individual allele is significantly preferentially transmitted from parents to affected offspring, the difference in the frequency of that allele would be sufficiently large to be detected with pooling in most situations. We propose recommendations for disequilibrium mapping with pooling in which both case-control samples and trios are used in an initial screen and markers are genotyped individually only if they satisfy very relaxed criteria for statistical significance. The use of case-control samples should reduce the false-negative rate as the differences in allele frequencies between cases and controls are twice as high in the presence of the same genetic effect. The use of trios will confirm or reject any suggested differences, thus reducing the false-positive rate that can be created by hidden population stratification.

Bipolar Disorder↗
PubMed1999

Expression of insulin growth factor-1 splice variants and structural genes in rabbit skeletal muscle induced by stretch and stimulation.

1. Skeletal muscle is a major source of circulating insulin growth factor-1 (IGF-1), particularly during exercise. It expresses two main isoforms. One of the muscle IGF-1 isoforms (muscle L.IGF-1) is similar to the main liver IGF-1 and presumably has an endocrine action. The other muscle isoform as a result of alternative splicing has a different 3' exon sequence and is apparently designed for an autocrine/paracrine action (mechano-growth factor, MGF). Using RNase protection assays with a probe that distinguishes these differently spliced forms of IGF-1, their expression and also the expression of two structural genes was measured in rabbit extensor digitorum longus muscles subjected to different mechanical signals. 2. Within 4 days, stretch using plaster cast immobilization with the limb in the plantar flexed position resulted in marked upregulation of both forms of IGF-1 mRNA. Electrical stimulation at 10 Hz combined with stretch (overload) resulted in an even greater increase of both types of IGF-1 transcript, whereas electrical stimulation alone, i.e. without stretch, resulted in no significant increase over muscle from sham-operated controls. Previously, it was shown that stretch combined with electrical stimulation of the dorsiflexor muscles in the adult rabbit results in a marked increase in muscle mass involving increases in both length and girth, within a few days. The expression of both systemic and autocrine IGF-1 growth factors provides a link between the mechanical signal and the marked increase in the structural gene expression involved in tissue remodelling and repair. 3. The expression of the beta actin gene was seen to be markedly upregulated in the stretched and stretched/stimulated muscles. It was concluded that the increased expression of this cytoskeletal protein gene is an indication that the production of IGF-1 may initially be a response to local damage. 4. Switches in muscle fibre phenotype were studied using a specific gene probe for the 2X myosin heavy chain gene. Type 2X expression was found to decrease markedly with stimulation alone and when electrical stimulation was combined with stretch. Unlike the induction of IGF-1 and beta actin, the decreased expression of the 2X myosin mRNA was less marked in the 'stretch only' muscles. This indicates that the interconversion of fibre type 2X to 2A may in some situations be commensurate with, but not under the control of IGF-1.

Actins↗
PubMed1999

No association between a polymorphic CAG repeat in the human potassium channel gene hKCa3 and bipolar disorder.

A recent case-control study suggested that modest enlargements of a CAG repeat in the hKCa3 potassium channel may be associated with bipolar disorder. We tried to replicate this result in a UK Caucasian sample of 203 DSM-IV bipolar I disorder patients and 206 controls group-matched for age and sex. Using the same model of analysis as the earlier study, bipolar probands did not have a higher frequency of alleles with greater than 19 repeats than controls (chi2 = 1.44, 1 df, P = 0.23). Similarly, comparison of the distributions of repeat sizes between probands and controls did not approach statistical significance (Mann-Whitney U test, P = 0.35). We conclude that our data provide no support for the hypothesis that variation at the hKCa3 gene contributes to susceptibility to bipolar disorder.

Adult↗
PubMed1999

Soybean isoflavones trigger a calcium influx in Phytophthora sojae.

Both the motile zoospores and the hyphal germ tubes of Phytophthora sojae respond chemotropically to the soybean isoflavones daidzein and genistein. The role of Ca(2+) in the cellular response to these host signals was investigated by using X-ray microanalysis of cells to monitor net changes in cellular levels of Ca(2+) and by quantifying the effects of exogenous Ca(2+) and daidzein on the developmental fate of encysted zoospores. Confirmation that isoflavones trigger a net influx of Ca(2+) into the cell was demonstrated by X-ray microanalysis of individual encysted zoospores. Zoospores exposed to 10 mM Ca(2+) and 1 microM daidzein at the time of encystment formed cysts that contained more Ca(2+) than zoospores exposed to Ca(2+) alone. The magnitude of internal Ca(2+) stores appears to be a determining factor affecting the developmental fate of P. sojae cysts.

Calcium↗
PubMed1999

Genotyping single nucleotide polymorphisms by primer extension and high performance liquid chromatography.

We have investigated the possibility of genotyping single nucleotide polymorphisms (SNPs) by primer extension and high performance liquid chromatography (HPLC). Using three polymorphisms of current interest to our group (an A/G polymorphism in the proneurotensin gene and A/G and T/C polymorphisms in the 5HT2a receptor gene), we show that robust signal is obtained using this simple analytic method which has the added advantages that sample loading and analysis are essentially automated, analytic time is brief, and no further purification step after primer extension is required. We also show that all stages of the HPLC-primer extension genotyping can be multiplexed which, together with automation, suggests that this system may be suitable for linkage studies based upon emerging SNP maps.

Base Sequence↗
PubMed1999

Analysis of the 60 S ribosomal protein L27a (L29) gene of Trypanosoma brucei.

The Trypanosoma brucei gene encoding the 60 S ribosomal protein L27a (L29) homologue has been cloned and characterised. The complete open reading frame encodes a small basic protein of 145 amino acids with a predicted molecular weight of 15,950. The L27a amino acid sequence shares 45-58% identity with other L27a (L29) homologues. Southern blot hybridisation suggests that the gene is present in multiple copies. Northern blot analysis of RNA from three T. brucei life cycle stages show that mRNA levels are two-fold higher in procyclic than in early or late bloodstream stages. This infers that this highly conserved ribosomal protein may play an important role in translational regulation through the life cycle of trypanosomes.

Amino Acid Sequence↗
PubMed1999

An objective scoring system for laparoscopic cholecystectomy.

BACKGROUND: Direct observation with structured criteria for performance is the most reliable and valid method of assessing technical skill during operative procedures. We developed such a system to evaluate technical performance during a laparoscopic cholecystectomy. The reliability and validity of the system were tested by analyzing the correlation among three observers in a multicenter study and comparing performance with years of surgical experience. STUDY DESIGN: Thirty consecutive cases of laparoscopic cholecystectomy were recorded on videotape, 10 from each of 3 institutions. Independent scores were generated by three observers examining each of the videotapes, providing a total of 90 scores. Points were awarded for successful completion of each of 23 different steps required to perform a laparoscopic cholecystectomy. Error points were tabulated based on the frequency and relative severity of each of 21 potential technical mistakes during the operation. The final score was assumed to be a relative measure of technical skill and was derived by subtracting error points from points awarded for completion of each step of the procedure. Pearson correlation coefficients were used to assess agreement among examiners and correlation with year of surgical experience. RESULTS: Agreement in final scores among the three observers was excellent (r = 0.74-0.96) despite the fact that one observer assigned significantly fewer error points. Correlation between year of experience and two-handed technique scoring was good (r = 0.5, p = 0.057), but the correlation between experience and one-handed technique scores was poor (r = 0.02). CONCLUSIONS: The technical skills required to perform laparoscopic cholecystectomy can reliably be measured using this tool. This method can be used to track the learning curve of surgeons in training, evaluate the efficacy of alternative training tools, and provide a means of self-assessment for the trainee.

Cholecystectomy, Laparoscopic↗