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P Fawcett

Publications and source records attributed to P Fawcett.

At least 19 recordsLinked to original sources
PubMed2001

Genome-wide analysis of the general stress response in Bacillus subtilis.

Bacteria respond to diverse growth-limiting stresses by producing a large set of general stress proteins. In Bacillus subtilis and related Gram-positive pathogens, this response is governed by the sigma(B) transcription factor. To establish the range of cellular functions associated with the general stress response, we compared the transcriptional profiles of wild and mutant strains under conditions that induce sigma(B) activity. Macroarrays representing more than 3900 annotated reading frames of the B. subtilis genome were hybridized to (33)P-labelled cDNA populations derived from (i) wild-type and sigB mutant strains that had been subjected to ethanol stress; and (ii) a strain in which sigma(B) expression was controlled by an inducible promoter. On the basis of their significant sigma(B)-dependent expression in three independent experiments, we identified 127 genes as prime candidates for members of the sigma(B) regulon. Of these genes, 30 were known previously or inferred to be sigma(B) dependent by other means. To assist in the analysis of the 97 new genes, we constructed hidden Markov models (HMM) that identified possible sigma(B) recognition sequences preceding 21 of them. To test the HMM and to provide an independent validation of the hybridization experiments, we mapped the sigma(B)-dependent messages for seven representative genes. For all seven, the 5' end of the message lay near typical sigma(B) recognition sequences, and these had been predicted correctly by the HMM for five of the seven examples. Lastly, all 127 gene products were assigned to functional groups by considering their similarity to known proteins. Notably, products with a direct protective function were in the minority. Instead, the general stress response increased relative message levels for known or predicted regulatory proteins, for transporters controlling solute influx and efflux, including potential drug efflux pumps, and for products implicated in carbon metabolism, envelope function and macromolecular turnover.

Bacillus subtilis↗
PubMed2001

A three-protein inhibitor of polar septation during sporulation in Bacillus subtilis.

We present evidence for a three-protein inhibitor of polar division that locks in asymmetry after the formation of a polar septum during sporulation in Bacillus subtilis. Asymmetric division involves the formation of cytokinetic Z-rings near both poles of the developing cell. Next, a septum is formed at one of the two polar Z-rings, thereby generating a small, forespore cell and a mother cell. Gene expression under the control of the mother-cell transcription factor sigmaE is needed to block cytokinesis at the pole distal to the newly formed septum. We report that this block in polar cytokinesis is mediated partly by sigmaE-directed transcription of spoIID, spoIIM and spoIIP, sporulation genes that were known to be involved in the subsequent process of forespore engulfment. We find that a spoIID, spoIIM and spoIIP triple mutant substantially mimicked the bipolar division phenotype of a sigmaE mutant and that cells engineered to produce SpoIID, SpoIIM and SpoIIP prematurely were inhibited in septum formation at both poles. Consistent with the hypothesis that SpoIID, SpoIIM and SpoIIP function at both poles of the sporangium, a GFP--SpoIIM fusion localized to the membrane that surrounds the engulfed forespore and to the potential division site at the distal pole.

Bacillus subtilis↗
PubMed2001

Carpal tunnel syndrome: the correlation between outcome, symptoms and nerve conduction study findings.

A retrospective study was performed on 62 patients who had undergone carpal tunnel decompression surgery. Each patient was assessed in clinic, their case notes were reviewed and their electrophysiological results were analysed and graded according to severity. The median preoperative duration of symptoms was 2 years. No relationship was found between the nature or duration of pre-operative symptoms and the severity of the electrophysiological impairment. Furthermore, no relationship could be identified between pre-operative nerve conduction impairment and either successful outcome of surgery (defined as complete symptom relief) or time to resolution of symptoms after surgery.

Carpal Tunnel Syndrome↗
PubMed2000

The transcriptional profile of early to middle sporulation in Bacillus subtilis.

Spore formation by Bacillus subtilis is governed by global changes in gene transcription. We used nylon-substrate DNA arrays representing approximately 96% of the predicted open reading frames in the B. subtilis chromosome to compare the pattern of transcripts from wild-type cells with the pattern from cells mutant for the sporulation transcription factors Spo0A or final sigma(F). We found 520 genes whose transcript levels were at least 3-fold dependent on Spo0A but not on final sigma(F), and an additional 66 genes whose transcript levels were dependent upon both regulatory proteins. Two strategies were used to help assign genes to the direct control of a particular developmental regulatory protein. In one approach, we analyzed the effects on global gene expression of artificially producing a constitutively active form of Spo0A during growth. In a second approach, Hidden Markov models were used to identify promoters likely to be activated by Spo0A, final sigma(F), or a third sporulation transcription factor, final sigma(E). In addition to detecting known sporulation genes, we identified many genes of unknown function whose patterns of expression and regulation suggest that they could be involved in sporulation. Disruption of two such newly identified genes, yabP and yabQ, blocked sporulation at a late stage.

Amino Acid Sequence↗
PubMed1999

A family of membrane-embedded metalloproteases involved in regulated proteolysis of membrane-associated transcription factors.

We present evidence that the sporulation protein SpoIVFB of Bacillus subtilis is a member of a newly recognized family of metalloproteases that have catalytic centers adjacent to or within the membrane. SpoIVFB is required for converting the membrane-associated precursor protein, pro-sigma(K), to the mature and active transcription factor sigma(K) by proteolytic removal of an N-terminal extension of 20 amino acids. SpoIVFB and other family members share the conserved sequence HEXXH, a hallmark of metalloproteases, as well as a second conserved motif NPDG, which is unique to the family. Both motifs, which are expected to form the catalytic center of the protease, overlap hydrophobic segments that are predicted to be separate transmembrane domains. The only other characterized member of this family of membrane-embedded metalloproteases is the mammalian Site-2 protease (S2P), which is required for the intramembrane cleavage of the eukaryotic transcription factor sterol regulatory element binding protein (SREBP). We report that amino acid substitutions in the two conserved motifs of SpoIVFB impair pro-sigma(K) processing and sigma(K)-directed gene expression during sporulation. These results and those from a similar analysis of S2P support the interpretation that both proteins are founding members of a family of metalloproteases involved in the activation of membrane-associated transcription factors. Thus, the pathways that govern the activation of the prokaryotic transcription factor pro-sigma(K) and the mammalian transcription factor SREBP not only are analogous but also use processing enzymes with strikingly homologous features.

Amino Acid Motifs↗
PubMed1999

A morphological analysis of the macro motor unit potential.

The technique of macro EMG is used to investigate the motor unit architecture in a number of pathological conditions. Amplitude and area are the most commonly used criteria, but these parameters alone are not sufficient to assess the complexity of the macro MUP morphology. In an attempt to examine the morphology of the macro MUP in more detail, additional measures were investigated including, (i) average power, (ii) duration, and (iii) number of phases. Macro MUP duration was defined as the time parameter that contains a particular fraction (90%) of the total power of the potential. The above mentioned parameters were evaluated for normal subjects and for patients suffering with motor neuron disease (MND), spinal muscular atrophy (SMA), and Becker's muscular dystrophy (BMD). It is shown that high amplitude and average power macro MUPs give shorter macro MUP duration than macro MUPs with normal amplitude. In contrast, in low amplitude macro MUPs there is a tendency towards a higher duration measure, as compared with the duration of the normal amplitude macro MUPs. Also, t-test results for the duration measure gave a significant difference between the NOR-MND, and no significant difference between the NOR-BMD and NOR-SMA groups at P<0. 05. Significant difference between the NOR and the three disease groups investigated was obtained for the parameters log amplitude, log area, and log average power. The number of phases was not significantly different between the NOR and the rest of the groups. In conclusion, the average power and duration parameters can possibly be used as additional discriminators to detect abnormalities of the macro motor unit potential in both needle and surface EMG but further investigation is necessary.

Biopsy↗
PubMed1998

Can medical audit change electromyographic practice?

Considerable variation in EMG practice has been described previously. Since 1992, 7 clinical neurophysiologists from 6 European countries prospectively collected electromyographic (EMG) examinations. The aim of this study was to examine whether several years of mutual influence among physicians using medical audit resulted in a more uniform EMG practice. We studied whether there was a change in the number of examinations per patient and the techniques used from the first 12 to the last 12 EMG examinations on patients with polyneuropathy. For F-wave studies and motor nerve studies, there was a clear change towards a more uniform practice. For sensory nerve conduction studies and muscle studies, there were only minor changes. With regard to examination techniques, there was a reduction in the use of more time-consuming examination techniques (near-nerve sensory studies and quantitative muscle studies). It seems possible to change the EMG practice of individual physicians by international collaboration and medical audit. However, until now most changes have been minor and large differences in European EMG practices persist. The diversity of practices suggests a need for studies on the optimal application of existing examination techniques.

Electromyography↗
PubMed1998

The Bacillus SpoIIGA protein is targeted to sites of spore septum formation in a SpoIIE-independent manner.

The process of bacterial cell division involves the assembly of a complex of proteins at the site of septation that probably provides both the structural and the cytokinetic functions required for elaboration and closure of the septal annulus. During sporulation in Bacillus subtilis, this complex of proteins is modified by the inclusion of a sporulation-specific protein, SpoIIE, which plays a direct role in gene regulation and also has a genetically separable role in determining the gross structural properties of the specialized sporulation septum. We demonstrate by both green fluorescent protein (GFP) fusions and indirect immunofluorescence microscopy that SpoIIGA, a protein required for proteolytic cleavage of pro-sigmaE, is also targeted to the sporulation septum. Septal localization of SpoIIGA-GFP occurred even in the structurally abnormal septum formed by a SpoIIE null mutant. We also report the isolation of a spoIIGA homologue from Bacillus megaterium, a species in which the cells are significantly larger than those of B. subtilis. We have exploited the physical dimensions of the B. megaterium sporangium, in conjunction with wide-field deconvolution microscopy, to construct three-dimensional projections of sporulating cells. These projections indicate that SpoIIGA-GFP is initially localized in an annulus at the septal periphery and is only later localized uniformly throughout the septa. Localization was also detected in a B. subtilis spo0H null strain that fails to construct a spore septum. We propose that SpoIIGA is sequestered in the septum by an interaction with components of the septation machinery and that this interaction begins before the construction of the asymmetric septum.

Amino Acid Sequence↗
PubMed1995

Variation in performance of the EMG examination at six European laboratories.

The quality of the EMG examination might be improved by standardization. However, knowledge about interlaboratory differences in the performance of the EMG examination is a prerequisite for standardization. The aim of this study was to describe differences in EMG techniques used and number of muscles and nerves examined per patient at 6 European EMG laboratories. The EMG results of 595 patients were prospectively sampled. The average number of muscles examined per patient in different disorders varied from laboratory to laboratory, for example from 3.0 to 10.8 muscles in anterior horn cell disorders and from 2.0 to 5.5 muscles in myopathies. The average number of muscles examined by quantitative EMG varied from 0 to 4.3 in anterior horn cell disorders and from 0.0 to 4.5 in myopathies. Also the average number of nerve segments examined per patient varied from laboratory for example from 2.7 to 17.7 for motor segments and from 3.1 to 9.0 for sensory segments in polyneuropathies. The laboratories that used needle electrodes for nerve conduction studies and quantitative analysis of individual motor unit potentials examined a smaller number of muscles and nerves than laboratories using surface electrodes for nerve conduction studies and qualitative EMG studies. The results of this study may have impact on guidelines and examination protocols as well as on quality assurance.

Electromyography↗
PubMed1995

Inter- and intraobserver variation in the interpretation of electromyographic tests.

This study was undertaken with the aim of evaluating inter- and intraobserver variation on the pathophysiological interpretation of individual electromyographic (EMG) tests on muscles and nerve segments. Seven physicians from 6 European EMG laboratories independently interpreted 81 EMG studies comprising 735 muscle tests and 726 tests on nerve segments. Pathophysiological conclusions were inferred from findings of these tests without considering clinical information. For most combinations of findings, both the inter- and intraobserver variations on the interpretation were low, suggesting that common criteria for pathophysiological interpretations were used and that these were used consistently. For some combinations of findings, however, there was disagreement on whether these indicated specific or unspecific pathophysiological changes. In particular disagreement on whether findings indicated demyelination may be of clinical significance. A large part of the intraobserver variation may be explained by a change towards more cautious interpretations during the study for most of the physicians. It is concluded that there is a need to seek for consensus on the pathophysiological interpretation of individual findings and for incentives to ensure consistency in interpretations. The fact that experienced physicians changed their ways to interpret findings during the study suggests that agreement may be improved globally.

Data Interpretation, Statistical↗
PubMed1995

Soluble interleukin-2 receptor as a predictor of neonatal sepsis.

We prospectively measured soluble interleukin-2 receptor levels in 56 premature infants with suspected sepsis and demonstrated significant differences between those with positive results on blood, urine, or cerebrospinal fluid cultures, and those with negative results. Soluble interleukin-2 receptor levels can be used to facilitate the diagnosis of sepsis in premature infants with negative blood culture results.

Humans↗
PubMed1995

Recurrent subarachnoid hemorrhage due to endometriosis.

A woman with a long history of menstruation-related headaches, at times associated with papilledema and brief episodes of unresponsiveness, was experiencing recurrent cryptogenic subarachnoid hemorrhage. Although the source of hemorrhage was never identified with certainty, strong circumstantial evidence suggested the presence of ectopic endometrial tissue in the spinal canal. Suppression of estrogen levels has prevented further episodes of hemorrhage.

Adult↗
PubMed1995

Quality assurance in clinical neurophysiology: the ESTEEM project example.

This paper describes the current status of the utilisation of clinical practice guidelines (protocols) in the ESTEEM project as one form of the clinical quality assurance procedures considered in the project. The performance of electrodiagnostic studies, in terms of which types of conclusions need to be inferred during the examination plan, is briefly described. The main focus of the paper is a description of an European multicentre clinical audit in the field of Clinical Neurophysiology, using a common data-entry protocol for prospective EMG case collection and assessment with the ultimate objective of building up a multicentre reference database of EMG cases.

Computer Communication Networks↗
PubMed1995

ESTEEM: a European telematic project for quality assurance within clinical neurophysiology.

From the prospective multi-center evaluation study of the decision support system KANDID, significant variations were revealed in local epidemiology, local examination techniques, local preferred examination protocols, and local diagnostic criteria among seven European EMG laboratories. A clinical network of eight Electromyographic (EMG) centers has, due to this study, harmonized terminology and the interpretation of EMG examinations. The ESTEEM project has, based on these specifications, developed the EMG-Platform for the local data acquisition, storage, interpretation, and telecommunication between the clinical ESTEEM centers. On this basis, a medical audit and consensus process across Europe is being carried out on a daily basis. This process has shown an impact on diagnostic criteria within the clinical group. This study has illustrates informatics as a necessary prerequisite for the quality assurance of clinical EMG practice.

Computer Systems↗
PubMed1994

Differences in the handling of the EMG examination at seven European laboratories.

This study was undertaken to analyse epidemiological and methodological differences in referral pattern, examination techniques and distribution of diagnoses among different European EMG laboratories. Seven European EMG laboratories filled in questionnaires and sampled 700 cases retrospectively. The use of needle or surface electrodes for nerve studies and the selection of quantitative techniques for muscle studies exhibited considerable variation. The pattern of referral varied with respect to the type of referral source and the neurological expertise of the referring physician. The proportion of patients without any neurophysiological abnormality ranged from 16 to 33%. The 3 most common diagnostic groups were mononeuropathies, polyneuropathies and radiculopathies although a great inter-laboratory variation was found. The proportion of patients with multiple diagnoses varied from 0 to 23% and most of these diagnoses were from a few known combinations. The presence of an inter-laboratory variation suggests that the quality of the EMG examination may be improved by focussing on the use of techniques, strategies and diagnostic criteria.

Electromyography↗
PubMed1994

ESTEEM (European Standardised Telematic Tool to Evaluate EMG Knowledge-Based Systems and Methods): AIM Project A2010.

ESTEEM is an AIM project which is primarily concerned with how to develop, integrate and clinically test knowledge-based systems for electromyography (EMG) in order to get them generally acceptable, useful and applicable into disseminated clinical routines. A medical workstation entitled the 'EMG-Platform' on which different kinds of application modules including KBSs can be interfaced to a kernel is being developed. Accordingly, an EMG communication protocol is being developed. The ESTEEM consortium is composed of a technical specialist group and a group of clinical experts in EMG from seven European countries. The last group has, besides extensive data collection for building up a multicentre EMG database, agreed on a common EMG terminology and a subsequent general EMG data set specification which covers the informatic needs for describing an EMG examination of different 'EMG schools'.

Electromyography↗