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P Watts

Publications and source records attributed to P Watts.

At least 19 recordsLinked to original sources
PubMed2001

An algorithm for mapping positively selected members of quasispecies-type viruses.

BACKGROUND: Many RNA viruses do not have a single, representative genome but instead form a set of related variants that has been called a quasispecies. The sequence variability of such viruses presents a significant bioinformatics challenge. In order for the sequence information to be understood, the complete mutational spectrum needs to be distilled to a biologically relevant and analyzable representation. RESULTS: Here, we develop a "selection mapping" algorithm--QUASI--that identifies the positively selected variants of viral proteins. The key to the selection mapping algorithm is the identification of particular replacement mutations that are overabundant relative to silent mutations at each codon (e.g., threonine at hemagglutinin position 262). Selection mapping identifies such replacement mutations as positively selected. Conversely, selection mapping recognizes negatively selected variants as mutational "noise" (e.g., serine at hemagglutinin position 262). CONCLUSION: Selection mapping is a fundamental improvement over earlier methods (e.g., dN/dS) that identify positive selection at codons but do not identify which amino acids at these codons confer selective advantage. Using QUASI's selection maps, we characterize the selected mutational landscapes of influenza A H3 hemagglutinin, HIV-1 reverse transcriptase, and HIV-1 gp120.

Algorithms↗
PubMed2001

Fragmentation and reactions of two isomeric O-alkyl S-(2-dialkylamino)ethyl methylphosphonothiolates studied by electrospray ionization/ion trap mass spectrometry.

An initial investigation into the electrospray ionization ion trap mass spectrometry (ESI/ITMS) of simple organophosphorus compounds [1] demonstrated that detailed structural information could be obtained by sequential fragmentation of the ions using collision induced dissociation (CID). Several novel fragmentations/rearrangements were observed and it was apparent that the full potential of this approach could not be exploited until a more detailed understanding of the ion fragmentations was obtained. Such an understanding will only result from a detailed study of a wide range of compounds. The present paper describes the investigation of two isomeric organophosphates of particular relevance to chemical warfare convention (CWC) considerations.

Chemical Warfare Agents↗
PubMed2001

Potent antiviral potamogetonyde and potamogetonol, new furanoid labdane diterpenes from Potamogeton malaianus.

New furanoid labdane diterpenes, potamogetonyde (3) and potamogetonol (4), together with two known compounds, potamogetonin (1) and 15,16-epoxy-12-oxo-8(17),13(16),14-labdatrien-20,19-olide (2), were isolated from the CH(2)Cl(2) extract of Potamogeton malaianus. The chemical structures of 1-4 were elucidated by the analyses of their spectral data, mainly by 1D and 2D NMR techniques. Potamogetonyde (3) and potamogetonol (4) exhibited potent antiviral (HSV-1) activity with respective IC(50) values of 8 and 3 microg/mL. Compounds 1-4 possessed cytotoxicity toward insect cells (fall armyworm and mosquito larvae, IC(50) of 11-72 microg/mL). Furanoid diterpenes 3 and 4 also exhibited cytotoxicity against the Vero cell line with respective IC(50)'s of 31 and 28 microg/mL, while 1 and 2 were inactive at 50 microg/mL. Compounds 1-4 were inactive (at 20 microg/mL) against KB and BC cell lines and showed only weak antimycobacterial activity against Mycobacterium tuberculosis H37Ra with minimum inhibitory concentrations of 50-100 microg/mL.

Aedes↗
PubMed2001

Carbamazepine: a 'blind' assessment of CVP-associated metabolism and interactions in human liver-derived in vitro systems.

1. The ability of various in vitro systems for CYP enzymes (computer modelling, human liver microsomes, precision-cut liver slices, hepatocytes in culture, recombinant enzymes) to predict various aspects of in vivo metabolism and kinetics of carbamazepine (CBZ) was investigated. 2. The study was part of the EUROCYP project that aimed to evaluate relevant human in vitro systems to study drug metabolism. 3. CBZ was given to the participating laboratories without disclosing its chemical nature. 4. The most important enzyme (CYP3A4) and metabolic route (10,11-epoxidation) were predicted by all the systems studied. 5. Minor enzymes and routes were predicted to a different extent by various systems. 6. Prediction of a clearance class, i.e. slow clearance, was correctly predicted by microsomes, slices, hepatocytes and recombinant enzymes (CYP3A4). 7. The 10,11-epoxidation of CBZ by the recombinant CYP3A4 was enhanced by the addition of exogenous cytochrome-b5, leading to a considerable over-prediction. 8. Induction potency of CBZ was predicted in cultured hepatocytes in which 7-ethoxycoumarin O-deethylase was used as an index activity. 9. It seems that for a principally CYP-metabolized substance such as CBZ, all liver-derived systems provide useful information for prediction of metabolic routes, rates and interactions.

Anticonvulsants↗
PubMed2001

An assessment of human liver-derived in vitro systems to predict the in vivo metabolism and clearance of almokalant.

The ability of various human derived in vitro systems to predict various aspects of the in vivo metabolism and kinetics of almokalant have been investigated in a multicenter collaborative study. Although almokalant has been withdrawn from further clinical development, its metabolic and pharmacokinetic properties have been well characterized. Studies with precision-cut liver slices, primary hepatocyte cultures, and hepatic microsomal fractions fortified with UDP-glucuronic acid all suggested that almokalant is mainly glucuronidated to the stereoisomers M18a and M18b, which is in good agreement with the results in vivo. Both in vivo and in vitro studies indicate that the formation of M18b dominates over that of M18a, although the difference is more pronounced with the in vitro systems. Molecular modeling, cDNA-expressed enzyme analysis, correlation analysis, and inhibition studies did not clearly indicate which P450 enzymes catalyze the oxidative pathways, which may indicate a problem in identifying responsible enzymes for minor metabolic routes by in vitro methods. All of the in vitro systems underpredicted the metabolic clearance of almokalant, which has previously been reported to be a general problem for drugs that are cleared by P450-dependent metabolism. Although few studies on in vivo prediction of primarily glucuronidated drugs have appeared, in vitro models may consistently underpredict in vivo metabolic clearance. We conclude that in vitro systems, which monitor phase II metabolism, would be beneficial for prediction of the in vivo metabolism, although all of the candidate liver-derived systems studied here, within their intrinsic limitations, provided useful information for predicting metabolic routes and rates.

Anti-Arrhythmia Agents↗
PubMed2000

Characterization of ricin heterogeneity by electrospray mass spectrometry, capillary electrophoresis, and resonant mirror.

Electrospray mass spectrometry (ES/MS), capillary-zone electrophoresis (CZE), capillary isoelectric focusing (CIEF), and multianalyte resonant mirror are used to evaluate the heterogeneity of samples of ricin toxins extracted from five horticultural varieties of Ricinus communis seeds: R. communis zanzibariensis, carmencita, impala, sanguineus, and gibsonii. The investigation is also extended to the geographical provenance of the beans. Combining mass spectrometry, CE techniques, and resonant mirror results in a powerful analytical tool capable to characterize and differentiate between different varieties of ricin toxins. Each technique complements the others, adding another level of information. This study reveals a large extent of heterogeneity for each cultivar, demonstrating that ricin toxins consist of a series of glycosylated proteins most likely originating from a multigene family. By combining these techniques, it is possible to differentiate between zanzibariensis and the other four varieties, and that variations in the functional characteristics may be observed between the different cultivars. This study demonstrates that knowledge of the variety of R. communis beans used and their geographical provenance is essential before any type of investigation of ricin toxins is carried out. Consequently, any unusual behavior observed can only be attributed to that particular cultivar studied and not automatically extended to include all R. communis varieties.

Biosensing Techniques↗
PubMed2000

Further evidence of autosomal dominant congenital zonular pulverulent cataracts linked to 13q11 (CZP3) and a novel mutation in connexin 46 (GJA3).

We describe a four-generation family with fully penetrant, autosomal dominant, congenital cataracts (ADCC), presenting with morphologically homogeneous "zonular pulverulent" cataracts (CZP) and typical early-onset phenotype. Linkage analysis was performed with a panel of polymorphic markers mapped to all genomic regions of ADCC susceptibility. Contiguous significant two-point lod scores were generated at autosomal region 13q11-q13 and further linkage and haplotype studies confined the disease locus to 13q11, supporting a previous linkage of CZP (specifically CZP3) to 13q11. Mutations in a gap-junction protein, connexin 46 (alphaa3 subunit or GJA3), have recently been reported as being linked to the 13q11 region. Mutational analysis of connexin 46 in our family revealed a C-->T at position 560 (P187L) of the cDNA sequence creating a novel MnlI restriction site that segregated with affected members of the pedigree. This family represents a second report of CZP3 linkage to 13q and is associated with a novel mutation in the connexin 46 (GJA3) gene.

Base Sequence↗
PubMed2000

Vitrectomy and lensectomy in the management of posterior dislocation of lens fragments.

PURPOSE: To study the visual results and complications in patients treated by vitrectomy and lensectomy for posterior dislocation of lens fragments during phacoemulsification. SETTING: University Hospital of Wales, Cardiff, United Kingdom. METHODS: This retrospective study was carried out between 1995 and 1998. Eighteen patients had a vitrectomy and lensectomy for posterior dislocation of lens fragments. The referral patterns, the presenting features, and the complications were recorded. The patients were invited for a final review to assess and record the final visual outcome and for a detailed ocular examination. RESULTS: The median age of the patients was 76 years. The youngest patient was 62 years and the oldest, 87 years. The median time of referral was 1 day (range 0 to 67 days). The median timing of the surgery was 6 days (range 2 to 77 days); however, 5 patients had a vitrectomy-lensectomy performed at the time of cataract surgery (day 0). Uveitis was present in 100% of patients, corneal edema in 76.0%, and ocular hypertension in 38.4%. Median follow-up was 12 months (range 6 to 34 months). Visual acuity was 6/12 or better in 83.3% of patients. Two patients were treated for retinal tears, 2 had postoperative uveitis, 2 had macular pucker, and 2 had ocular hypertension. There was no statistically significant association between final visual outcome and grade of the surgeon performing the cataract operation, the presence of an intraocular lens at the time of cataract surgery, the timing of the vitrectomy-lensectomy, or the presence of previtrectomy uveitis or high intraocular pressure (IOP). CONCLUSIONS: Early recognition of dislocated lens fragments and prompt assessment for vitrectomy-lensectomy produced excellent visual results and few complications. The corneal edema, uveitis, and high IOP resolved with the vitrectomy-lensectomy.

Aged↗
PubMed2000

Linkage analysis in an autosomal dominant 'zonular nuclear pulverulent' congenital cataract, mapped to chromosome 13q11-13.

PURPOSE: To determine by linkage analysis the chromosomal locus responsible for autosomal dominant congenital cataract (ADCC) in a four-generation Welsh pedigree. METHODS: The family pedigree was traced through two members of the family attending the hospital for treatment of their cataracts. Twenty-five members of the family were examined ophthalmologically and blood was collected with consent for genetic linkage analysis. RESULTS: Fifteen members of this family were known to have bilateral congenital cataracts, of whom 11 had a cataract extraction prior to examination. The youngest member of the pedigree was 5 years old and the oldest was 78 years old. Four children, unoperated at the time of this study, had a phenotypically identical morphology of their zonular pulverulent congenital cataracts. The known loci for congenital cataract were excluded. Significant lod scores for markers in the 13q11-13 region were detected with a Zmax of 3.59 D13S1236 (theta = 0.00). CONCLUSIONS: We report linkage of an ADCC of the zonular pulverulent type to chromosome 13q11-13 in a four-generation family.

Adolescent↗
PubMed2000

In vitro fertilisation and stage 3 retinopathy of prematurity.

PURPOSE: To re-examine the risk of children born by assisted conception developing stage 3 retinopathy of prematurity (ROP) and to define whether the risk of ROP varies with the method of assisted conception. METHODS: This was a retrospective study carried out between December 1995 and December 1998 of infants in a single neonatal unit serving the Brent and Harrow area of North West Thames requiring screening and treatment of ROP. The infants screened were identified from the ROP screening database. Those conceived by in vitro fertilisation (IVF) and other forms of assisted conception were identified by reviewing the neonatal notes and the maternal obstetric records. Birth weight, gestational age and the type of assisted conception were recorded. The presence or absence of any stage of ROP, its location and severity and the cases requiring treatment were recorded. RESULTS: One hundred and seventy-nine infants fulfilled the screening criteria during this period. Acute ROP was detected in 32.4% (58 infants) and stage 3 ROP developed in 15.6% (28 infants). Twenty-one infants (11.7%) were born after assisted conception, with 12 (6.7%) being conceived by IVF. The others were conceived on clomiphene (8) or after intrauterine insemination (1). Assisted conception accounted for 21.4% of all those reaching stage 3 disease and 28.6% of those infants requiring treatment. Of the 12 infants conceived by IVF, 41.6% (5 infants) developed acute ROP which progressed to threshold ROP in all infants (100%). Of the assisted conception babies requiring treatment for ROP, 83.3% were conceived by IVF. The other child had been conceived on clomiphene. The gestational age and birth weight of the IVF infants reaching stage 3 ROP were 26.6 +/- 0.89 weeks and 937 +/- 170.2 g. The gestational age and birth weight in the rest of the infants reaching stage 3 ROP were lower than in those conceived by assisted conception (25.739 +/- 1.13 weeks and 735.29 +/- 117.70 g); however, this did not approach statistical significance (p = 0.35 and p = 0.13, respectively). CONCLUSIONS: In this study 11.7% of the group requiring screening were conceived by assisted conception. Of all babies requiring treatment for ROP, 28.6% were born after assisted conception. Of the assisted conception group, 83.3% were conceived by IVF. Assisted conception using IVF rather than other techniques appears to be the major risk factor for the development of threshold ROP. We would advise increased vigilance when screening babies conceived by the IVF methods of assisted conception.

Birth Weight↗
PubMed2000

Tarantula keratouveitis.

PURPOSE: To report a case of chronic bilateral keratouveitis, which was initiated after contact with a pet tarantula. METHODS: A 16-year-old male presented with a photophobia and redness of his eyes two days after handling a tarantula. He was found to have a number of linear corneal foreign bodies with subepithelial infiltrates. The infiltrates were found at varying levels of the corneal stroma with deposits on the endothelium. The anterior chamber had a mild cellular reaction. RESULTS: He was treated with topical steroid drops, which made him asymptomatic. However, he continued to have a mild persistent keratitis and iritis four months after the onset. CONCLUSION: Tarantula hairs may be associated with a chronic keratouveitis, which is usually self-limiting and responds well to treatment with topical steroids. Tarantula pet owners should be forewarned of the ocular dangers associated with handling these spiders.

Adolescent↗
PubMed2000

Intraventricular haemorrhage and stage 3 retinopathy of prematurity.

BACKGROUND/AIMS: A recent report has highlighted the decreasing prevalence in recent years of severe intraventricular haemorrhage (IVH) in very low birthweight (VLBW) infants (<1500 g). This study attempted to identify the severity of the grade of IVH in infants with stage 3 retinopathy of prematurity (ROP), and to re-examine the association between threshold ROP and IVH. METHODS: This was a retrospective study carried out over 3 years, between December 1995 and December 1998 of neonates admitted to a single neonatal intensive care unit. 28 infants with stage 3 ROP were identified from the ROP screening database. Cranial ultrasound scans were available on 24 of these infants. The scans were reviewed and the severity of IVH was graded from grade 1 to grade 4. The birth weight, sex, ethnic origin, and gestational age of the babies were recorded. The number of infants progressing to threshold disease and the treatment provided was documented. RESULTS: The 24 infants had a median gestational age of 26 weeks (range 24-28 weeks) and a median birth weight of 762.5 g (range 540-1010 g). 17 infants were treated for threshold disease. 13 infants (54.2%) had IVH, of these eight (61.5%) had grade 1, two (15.4%) had grade 2, one (7.7%) had grade 3, and two (15.4%) had grade 4. 12 of the 13 infants (92.3%) with IVH had treatment with laser or cryotherapy for ROP compared with five of the remaining 11 infants (p = 0.023, Fisher's exact test). These data provide little evidence of any association between IVH and each of ethnic origin (p = 0.856), sex (p = 1), birth weight, or gestational age (p = 0.56 and p = 0.06 respectively) in infants with stage 3 ROP. CONCLUSIONS: These data provide strong evidence (p = 0. 023) of an association between the presence of IVH and treatment of threshold ROP. Although the numbers in this study are small the majority of infants with stage 3 ROP had grade 1 IVH, which heralds a more favourable neurological outcome. An association between the severity of ROP and severity of IVH was not demonstrated. With improvements in neonatal care and a reduction in the prevalence of severe IVH, there appears to be a weakening of the previously reported association between severe IVH and severe ROP. However, the presence of even a minor grade of IVH may be a significant risk factor for threshold ROP once stage 3 disease is encountered.

Birth Weight↗
PubMed1999

Potential of polymeric lamellar substrate particles (PLSP) as adjuvants for vaccines.

In recent years microspheres or microparticles produced from biodegradable polymers such as poly(D,L-lactide) (PLA) and poly(D, L-lactide-co-glycolide) (PLGA) containing encapsulated vaccine antigens have been investigated for administration via parenteral, oral, and intranasal routes. These microparticles allow the controlled release of vaccines with an aim to reduce the number of doses for primary immunisation or to develop single dose vaccines. The polymer materials have been widely regarded as being of minimal toxicity. Evaluation of candidate systems in animal studies have shown antibody levels and cell responses similar to or greater than those observed with adjuvants such as alum. However, there are concerns regarding the integrity and immunogenicity of the antigen during the encapsulation process when the antigen is exposed to organic solvents, high shear stresses and the exposure of antigen to low pH which is caused by polymer degradation. An alternative approach would be to adsorb antigens to the surface of biodegradable polymer particles. Polymeric lamellar substrate particles (PLSP), produced by a simple precipitation of PLA, are suitable for this purpose. The adsorption of antigens onto these particles is a simple procedure. It avoids pH changes due to bulk polymer degradation and the use of solvents and therefore will be less damaging to the vaccine. Moreover, such systems will be much easier to scale up for a clinical study and eventual manufacture. The aim of this article is to discuss the preparation and physical characteristics of PLSP, antigen adsorption, in vivo efficacy of PLSP antigen systems and to consider the potential of PLSP as controlled release adjuvants for protein, peptide or viral vaccines.

Adjuvants, Immunologic↗
PubMed1999

Photoscreening for refractive errors in children and young adults with severe learning disabilities using the MTI photoscreener.

PURPOSE: To test the potential ability of the MTI photoscreener to facilitate screening for significant refractive errors in children and young adults with severe learning disabilities. METHODS: Thirty-eight patients with severe learning disabilities from a special school were examined with the photoscreener, and underwent cycloplegic refraction, an ophthalmological and an orthoptic examination. The age at examination, the cause of learning disability, the pupil size, the number of photographs required for accurate interpretation, the co-operation of the subject and the presence or absence of strabismus were recorded. An educational psychologist had performed a psychological assessment on all the children. The results of the cycloplegic retinoscopy were compared with the photorefraction results. RESULTS: A photorefraction was possible in 37 patients and cycloplegic refraction in all the patients. The patients had severe learning difficulties with an intelligence quotient of less than 50. All the patients had behavioural problems, 9 patients had associated cerebral palsy, 8 had chronic epilepsy, 1 patient was brain damaged from a non-accidental injury and 1 from a road traffic accident. The mean age of the patients was 10.0 +/- 4.9 years (range 3-18 years), the average pupil diameter during photoscreening was 6.1 +/- 0.9 mm (range 4-8 mm) and the average number of photographs required for each subject was 2.1 +/- 0.9 (range 1-4). The photoscreener detected 10 patients with a manifest strabismus. There was one false positive and one false negative result giving a sensitivity of 92.8% and a specificity of 90%. CONCLUSION: The examination of children with severe learning disabilities for refractive errors can be extremely difficult. The MTI photoscreener is an effective means of screening such children and young adults for refractive errors and strabismus so that the children with these abnormalities may be targeted for a more detailed evaluation.

Adolescent↗
PubMed1999

Estimation of the retinal nerve fibre layer thickness in the papillomacular area of long standing stage IV macular holes.

AIM: To compare the thickness of the retinal nerve fibre layer (RNFL) in the papillomacular area of patients with long standing stage IV macular holes with age matched controls, using a scanning laser polarimeter. METHODS: The nerve fibre analyser (NFA) was used to measure the mean thickness of the RNFL around the optic nerve head, the thickness values of temporal and nasal 45 degrees sectors and the integral values in 10 patients with macular holes and in 10 age matched controls. RESULTS: The mean RNFL thickness around the optic nerve head was 79.71 (SD 15.06) microm in the macular hole group and 75.1 (10.8) microm in the control group (p = 0.44). The mean thickness in the temporal sector was 63.69 (12.08) microm in the macular hole group and 58.65 (8.9) microm in the control group (p = 0.3). The mean ratio between the temporal and nasal sector thickness values was 0.8441 in the macular hole group and 0.7819 in the controls (p = 0.42). CONCLUSIONS: There was no significant difference in the thickness of the RNFL in the papillomacular area in the two groups. This suggests that there may be no changes in the thickness of the RNFL in patients with long standing macular holes.

Adult↗
PubMed1999

Development of an instrument to measure community acceptance of nurse practitioners and physician assistants.

The purpose of this study was to identify the significant dimensions of the concept of community acceptance of nurse practitioners/physician's assistants and to construct a reliable and valid instrument which would reflect these dimensions. The methodological approach included: conceptualization of categories, development of items for each category, development of the tool, administration of the tool, and psychometric analysis of results. Community input through focus-group interviews and post-administration questions provided qualitative data. The survey tool, consisting of items in four conceptualized categories (knowledge, access, competence, and trust), was administered in five rural communities. The responses of 967 residents were analyzed through factor analysis. The criterion, eigenvalue > or = 1.0, resulted in seven factors. Oblique rotation was applied to the seven factors and marker variables (loadings > .70) facilitated the identification of the underlying dimensions of each factor. Overall, 98% of the items assigned to the original categories were maintained after factor analysis. The identification of these dimensions helped to simplify the description and understanding of community acceptance of nurse practitioners and physicians' assistants. Community acceptance of these advanced health care providers is a necessary precursor to use of services.

Adult↗