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Biomedical subjects

P Taylor

Publications and source records attributed to P Taylor.

At least 109 records · Page 6Linked to original sources
PubMed2000

Common EF-hand motifs in cholinesterases and neuroligins suggest a role for Ca2+ binding in cell surface associations.

Comparisons of protein sequence via cyclic training of Hidden Markov Models (HMMs) in conjunction with alignments of three-dimensional structure, using the Combinatorial Extension (CE) algorithm, reveal two putative EF-hand metal binding domains in acetylcholinesterase. Based on sequence similarity, putative EF-hands are also predicted for the neuroligin family of cell surface proteins. These predictions are supported by experimental evidence. In the acetylcholinesterase crystal structure from Torpedo californica, the first putative EF-hand region binds the Zn2+ found in the heavy metal replacement structure. Further, the interaction of neuroligin 1 with its cognate receptor neurexin depends on Ca2+. Thus, members of the alpha,beta hydrolase fold family of proteins contain potential Ca2+ binding sites, which in some family members may be critical for heterologous cell associations.

Amino Acid Sequence↗
PubMed2000

Evolutionary implications of phenotypic plasticity in the hindlimb of the lizard Anolis sagrei.

Species of Anolis lizards that use broad substrates have long legs, which provide enhanced maximal sprint speed, whereas species that use narrow surfaces have short legs, which permit careful movements. We raised hatchling A. sagrei in terraria provided with only broad or only narrow surfaces. At the end of the experiment, lizards in the broad treatment had relatively longer hindlimbs than lizards in the narrow treatment. These results indicate that not only is hindlimb length a plastic trait in these lizards, but that this plasticity leads to the production of phenotypes appropriate to particular environments. Comparison to hindlimb lengths of other Anolis species indicates that the range of plasticity is limited compared to the diversity shown throughout the anole radiation. Nonetheless, this plasticity potentially could have played an important role in the early stages of the Caribbean anole radiation.

Adaptation, Physiological↗
PubMed2000

Analysis and synthesis of intonation using the Tilt model.

This paper introduces the Tilt intonational model and describes how this model can be used to automatically analyze and synthesize intonation. In the model, intonation is represented as a linear sequence of events, which can be pitch accents or boundary tones. Each event is characterized by continuous parameters representing amplitude, duration, and tilt (a measure of the shape of the event). The paper describes an event detector, in effect an intonational recognition system, which produces a transcription of an utterance's intonation. The features and parameters of the event detector are discussed and performance figures are shown on a variety of read and spontaneous speaker independent conversational speech databases. Given the event locations, algorithms are described which produce an automatic analysis of each event in terms of the Tilt parameters. Synthesis algorithms are also presented which generate F0 contours from Tilt representations. The accuracy of these is shown by comparing synthetic F0 contours to real F0 contours. The paper concludes with an extensive discussion on linguistic representations of intonation and gives evidence that the Tilt model goes a long way to satisfying the desired goals of such a representation in that it has the right number of degrees of freedom to be able to describe and synthesize intonation accurately.

Humans↗
PubMed2000

Diagnostically and experimentally useful panel of strains from the Burkholderia cepacia complex.

Two new species, Burkholderia multivorans and Burkholderia vietnamiensis, and three genomovars (genomovars I, III, and IV) currently constitute the Burkholderia cepacia complex. A panel of 30 well-characterized strains representative of each genomovar and new species was assembled to assist with identification, epidemiological analysis, and virulence studies on this important group of opportunistic pathogens.

Bacterial Typing Techniques↗
PubMed2000

Future prospects for anti-cytokine treatment.

The era of anti-cytokine treatment in rheumatology has just begun. The first generation therapeutic agents, biological agents that block tumour necrosis factor alpha such as monoclonal antibodies or receptor Ig fusion proteins are safe and effective, and so this has generated much interest in how to increase the benefit or deliver it more cost effectively. This article provides a personal view of the coming trends in anti-cytokine treatment. Which of these will be realised in the future will be of interest.

Antirheumatic Agents↗
PubMed2000

Trends in special (high-security) hospitals. 1: Referrals and admissions.

BACKGROUND: Special hospitals in England provide psychiatric care and treatment in high security. Their future is often questioned. AIMS: To test for variation in demand for high-security psychiatric services over one 10-year period. METHOD: This study was from the special hospitals' case registers and hospital records. The main measures were numbers and annual rates for referrals and beds offered; the Mental Health Act 1983 (MHA) classification of mental disorder; adjusted population rates by health region; admission episodes; legal category of detention; admission source and type of offence. RESULTS: Referrals to special hospitals showed no decrease during the 10 years; an apparent increase may reflect underrecording before 1992. Admissions fell by about 16% over the 10 years, but with regional variation. Women, civil cases, admissions under the MHA classifications of psychopathic disorder or mental impairment and directly from a court on a hospital order were most affected. There was an increase in admissions of pre-trial and sentenced male prisoners, and of transferred hospital order patients from other hospitals. CONCLUSIONS: There is continuing demand from all parts of the country for high-security hospital beds. The smaller numbers admitted appear to include more demanding cases.

Commitment of Persons with Psychiatric Disorders↗
PubMed2000

Trends in special (high-security) hospitals. 2: Residency and discharge episodes, 1986-1995.

BACKGROUND: It has been argued that many patients in special hospital beds do not need to be there. In the 1990s there were initiatives to discharge women and people with learning difficulties. AIMS: To test for trends in special hospital discharges and to examine annual resident cohorts. METHOD: This study was from case registers and hospital records. The main measures were numbers and annual rates for referrals and beds offered; the Mental Health Act 1983 (MHA) classification of mental disorder; adjusted population rates by region; admission episodes; legal category of detention; admission source and type of offence. RESULTS: The median annual number of residents was 1859 (range 1697-1910), with an 8% fall for the period. This particularly affected people in mental impairment categories. Numbers were sustained in the male mental illness groups. Discharges, mainly to other institutions, increased. There was no overall change over the 10 years in length of stay for treatment, but successive admission cohorts from 1986 did show some reduction, even with solely remand order cases excluded. CONCLUSIONS: Service planners need a longitudinal perspective on service use. Trends over 10 years to both fewer admissions and more discharges have reduced the special hospital population, but despite new treatments for schizophrenia, men under mental illness classification, as well as transfer from other secure settings, have gone against this trend.

Female↗
PubMed2000

An assessment of the potential effect of a teledermatology system.

The potential effect of a commercial teledermatology system was assessed. The system allowed general practitioners to send dermatologists a set of digital images, accompanied by a short patient history. Patients were seen, in the normal way, by consultant dermatologists. The system was then used to capture a set of images. These were viewed by two dermatologists, 13 months later. Reasonably high levels of agreement were found between the dermatologist seeing the patient and the dermatologist using the telemedicine system (77%). The two dermatologists were also asked to indicate whether, had the system been in use, the patient would have been seen urgently or routinely, or whether the general practitioner would have been advised that an outpatient appointment was not required. The results showed that fewer patients would have been called for urgent appointments (32% compared with 64%) and that 31% of cases could have been managed by the general practitioner. Assuming that the introduction of the system would have had no effect on the overall number of referrals, nor on the number of follow-up appointments, these figures suggest that the total number of appointments could be cut by 13%. It took approximately an hour to view 20 cases and it would be necessary to devote one consultant session a week to viewing images. This system would therefore not lead to significant savings, nor reduce the waiting list for outpatient appointments. The idea would have potential if the review of images could be made as easy as the triage of referral letters.

Dermatology↗
PubMed2000

Postoperative evaluation of patients following ophthalmic surgery.

We have used telemedicine to support the postoperative evaluation of patients who have had ophthalmic surgery. Mobile telemedicine workstations connected using three ISDN lines have enabled us to review patients at an outreach clinic on the first postoperative day. Video slit-lamp images of the patient are captured by a trained ophthalmic nurse at the outreach clinic and viewed by surgeons at Moorfields Eye Hospital in central London during live teleconsultations. During the study period, over 80 teleconsultations were carried out on postoperative cataract, trabeculectomy and combined procedures. Preliminary results are very encouraging. Although 8 (33%) of 24 patients were anxious about being involved in the teleconsultation, 20 (83%) had confidence in the system and only one (4%) found the experience unacceptable.

Eye Diseases↗
PubMed2000

An approach to proteomic analysis of human tumors.

A strategy for proteomic analysis of microdissected cells derived from human tumor specimens is described and demonstrated by using esophageal cancer as an example. Normal squamous epithelium and corresponding tumor cells from two patients were procured by laser-capture microdissection and studied by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Fifty thousand cells resolved approximately 675 distinct proteins (or isoforms) with molecular weights ranging between 10 and 200 kDa and isoelectric points of pH 3-10. Comparison of the microdissected protein profiles showed a high degree of similarity between the matched normal-tumor samples (98% identical). However, 17 proteins showed tumor-specific alterations, including 10 that were uniquely present in the tumors and seven that were observed only in the normal epithelium. Two of the altered proteins were characterized by mass spectrometry and immunoblot analysis and were identified as cytokeratin 1 and annexin I. Acquisition of 2D-PAGE protein profiles, visualization of disregulated proteins, and subsequent determination of the identity of selected proteins through high-sensitivity MS-MS microsequencing are possible from microdissected cell populations. These separation and analytical techniques are uniquely capable of detecting tumor-specific alterations. Continued refinement of techniques and methodologies to determine the abundance and status of proteins in vivo holds great promise for future study of normal cells and associated neoplasms. Mol.

Electrophoresis, Gel, Two-Dimensional↗
PubMed2000

Inactivation studies of acetylcholinesterase with phenylmethylsulfonyl fluoride.

Acetylcholinesterase (AChE), a serine hydrolase, is potentially susceptible to inactivation by phenylmethylsulfonyl fluoride (PMSF) and benzenesulfonyl fluoride (BSF). Although BSF inhibits both mouse and Torpedo californica AChE, PMSF does not react measurably with the T. californica enzyme. To understand the residue changes responsible for the change in reactivity, we studied the inactivation of wild-type T. californica and mouse AChE and mutants of both by BSF and PMSF both in the presence and absence of substrate. The enzymes investigated were wild-type mouse AChE, wild-type T. californica AChE, wild-type mouse butyrylcholinesterase, mouse Y330F, Y330A, F288L, and F290I, and the double mutant T. californica F288L/F290V (all mutants given T. californica numbering). Inactivation rate constants for T. californica AChE confirmed previous reports that this enzyme is not inactivated by PMSF. Wild-type mouse AChE and mouse mutants Y330F and Y330A all had similar inactivation rate constants with PMSF, implying that the difference between mouse and T. californica AChE at position 330 is not responsible for their differing PMSF sensitivities. In addition, butyrylcholinesterase and mouse AChE mutants F288L and F290I had increased rate constants ( approximately 14 fold) over those of wild-type mouse AChE, indicating that these residues may be responsible for the increased sensitivity to inactivation by PMSF of butyrylcholinesterase. The double mutant T. californica AChE F288L/F290V had a rate constant nearly identical with the rate constant for the F288L and F290I mouse mutant AChEs, representing an increase of approximately 4000-fold over the T. californica wild-type enzyme. It remains unclear why these two positions have more importance for T. californica AChE than for mouse AChE.

Acetylcholinesterase↗
PubMed2000

Postnatal developmental delay and supersensitivity to organophosphate in gene-targeted mice lacking acetylcholinesterase.

Acetylcholinesterase (AChE; EC 3.1.1.7) is the primary terminator of nerve impulse transmission at cholinergic synapses and is believed to play an important role in neural development. Targeted deletion of four exons of the ACHE gene reduced AChE activity by half in heterozygous mutant mice and totally eliminated AChE activity in nullizygous animals. Butyrylcholinesterase (EC 3.1.1.8) activity was normal in AChE -/- mice. Although nullizygous mice were born alive and lived up to 21 days, physical development was delayed. The neuromuscular junction of 12-day-old nullizygous animals appeared normal in structure. Nullizygous mice were highly sensitive to the toxic effects of the organophosphate diisopropylfluorophosphate and to the butyrylcholinesterase-specific inhibitor bambuterol. These findings indicate that butyrylcholinesterase and possibly other enzymes are capable of compensating for some functions of AChE and that the inhibition of targets other than AChE by organophosphorus agents results in death.

Acetylcholinesterase↗
PubMed2000

Subunit interface selective toxins as probes of nicotinic acetylcholine receptor structure.

The pentametric assembly of the nicotinic acetylcholine receptor with two of the five subunit interfaces serving as a ligand binding sites offers an opportunity to distinguish features on the surfaces of the subunits, and their ligand specificity characteristics. The receptor from mammalian muscle, with its circular order of homologous subunits (alphagamma alphadelta beta), assembles in a unique arrangement. The residues governing assembly can be ascertained through mutagenesis. Selectivity of certain natural toxins is sufficient to distinguish between sites at the alphagamma and alphadelta subunit interfaces. By interchanging residues on the gamma and delta subunits through mutagenesis, and ascertaining how they interact with the alpha subunit, determinants forming the binding sites can be delineated. The alpha-conotoxins show a 10,000-fold preference for the alphadelta over alphagamma subunit interface with alphaepsilon falling in between. The waglerins show a 2,000-fold preference for alphaepsilon over the alphagamma and alphadelta interfaces. Finally, the alpha-neurotoxin from N. mossambica mossambica shows a 10,000-fold preference for the alphagamma and alphadelta interfaces over alphaepsilon. Identification of interactive residues through mutagenesis, when coupled with homology modeling of domains and site-directed residue modification, has revealed important elements of receptor structure.

Animals↗
PubMed2000

CADMIUM II: acquisition and representation of radiological knowledge for computerized decision support in mammography.

CADMIUM II is a system for the interpretation of mammograms. A novel aspect of the system is that it combines symbolic reasoning with image processing, in contrast with most other approaches, which use only image processing and rely on artificial neural networks (ANNs) to classify mammograms. A problem of ANNs is that the advice they give cannot be traced back to communicable diagnostic inferences. Our approach is to provide advice based on explicit knowledge about the diagnostic process. To this end, we have conducted a knowledge elicitation study which looked at the descriptors used by expert radiologists when making diagnostic decisions about mammograms. The analysis of the radiologists' reports yielded a set of salient diagnostic features. These were used to inform the advice provided by the symbolic decision making component of CADMIUM II.

Breast Diseases↗