PubMed Health⌕ Search

Biomedical subjects

C Barrett

Publications and source records attributed to C Barrett.

At least 19 recordsLinked to original sources
PubMed1998

Sequence comparisons using multiple sequences detect three times as many remote homologues as pairwise methods.

The sequences of related proteins can diverge beyond the point where their relationship can be recognised by pairwise sequence comparisons. In attempts to overcome this limitation, methods have been developed that use as a query, not a single sequence, but sets of related sequences or a representation of the characteristics shared by related sequences. Here we describe an assessment of three of these methods: the SAM-T98 implementation of a hidden Markov model procedure; PSI-BLAST; and the intermediate sequence search (ISS) procedure. We determined the extent to which these procedures can detect evolutionary relationships between the members of the sequence database PDBD40-J. This database, derived from the structural classification of proteins (SCOP), contains the sequences of proteins of known structure whose sequence identities with each other are 40% or less. The evolutionary relationships that exist between those that have low sequence identities were found by the examination of their structural details and, in many cases, their functional features. For nine false positive predictions out of a possible 432,680, i.e. at a false positive rate of about 1/50,000, SAM-T98 found 35% of the true homologous relationships in PDBD40-J, whilst PSI-BLAST found 30% and ISS found 25%. Overall, this is about twice the number of PDBD40-J relations that can be detected by the pairwise comparison procedures FASTA (17%) and GAP-BLAST (15%). For distantly related sequences in PDBD40-J, those pairs whose sequence identity is less than 30%, SAM-T98 and PSI-BLAST detect three times the number of relationships found by the pairwise methods.

Databases, Factual↗
PubMed1998

Azocarbazole Polymethacrylates as Single-Component Electrooptic Materials.

A series of amorphous azobenzene and carbazole-containing polymers was prepared, which incorporates both electrooptic activity and photoconductivity into a single multifunctional structural unit. The polymers were cast as thin films and were shown to be suitable for photoinducing birefringence reversibly with polarized light, as well as for the inscription of photorefractive diffraction gratings after electric field poling. Since the polymer series encompasses a range of spacer lengths (from 3 to 10 methylene groups) between the multifunctional side chains and the polymer backbone, these materials are suitable for study of the influence of chromophore mobility on these optical phenomena. The extent of orientational order which could be photoinduced in the films was found to decrease with increasing spacer length, as did the photoconductivity and the photorefractive two-beam optical coupling gain. In thin films of polymers with the highest glass transition temperature, a birefringence of 0.065 could be photoinduced, with a time constant of <0.8 s. A two-beam optical gain of 0.024 µm-1 was also demonstrated in films of the polymer with the highest glass transition temperature, although this gain was exceeded by absorption losses.

Journal Article↗
PubMed1998

Monocyte chemoattractant protein 1 is responsible for macrophage recruitment following injury to sciatic nerve.

Following injury to the peripheral nervous system, circulating monocytes/macrophages are recruited to the damaged tissue, where they play vital roles during both nerve degeneration and subsequent regeneration. Monocyte chemoattractant protein-1 (MCP-1), a member of the C-C or beta-chemokine family, is a powerful leukocyte recruitment/activation factor that is relatively specific for monocytes/macrophages. Because these are the predominant leukocyte type recruited by injured nerve, we hypothesized that upregulation of MCP-1 expression is involved in recruitment of these cells. Indeed, assay of steady-state levels of MCP-1 mRNA in rat sciatic nerve during tellurium-induced primary demyelination indicated up-regulation of this chemokine with a peak after 3 days of tellurium exposure, preceding the peak of accumulation of phagocytic macrophages (assayed as lysozyme mRNA levels) by 6 days. Increasing levels of MCP-1 mRNA expression, induced by increasing levels of tellurium exposure, resulted in corresponding increases in subsequent recruitment of macrophages. In situ hybridization suggested that MCP-1 mRNA was localized in Schwann cells. No expression of MIP-2, which is a C-X-C or alpha-chemokine that is specific for recruitment of neutrophils, was detected, consistent with the lack of recruitment of significant numbers of these cells. In addition, we also investigated the response seen following nerve transection (axonal degeneration and secondary demyelination with no subsequent regeneration) and nerve crush (degeneration followed by regeneration). In these latter two nerve injury models, there was also a marked, early up-regulation of MCP-1 mRNA, with a time course that is compatible with a role for this chemokine in macrophage recruitment. We conclude that MCP-1 is involved in recruiting monocytes/macrophages to injured peripheral nerve and that the specificity of leukocyte types recruited results from specificity of chemokine production.

Animals↗
PubMed1998

Job satisfaction in preceptorship and its effect on the clinical performance of the preceptee.

This study was designed to examine the relationship between preceptor/preceptee job satisfaction and preceptee clinical performance. A correlational descriptive design using quantitative data was employed through a mailed survey. Seventy-nine questionnaires were mailed to preceptors, 100 to preceptees. The response rate for preceptors was 49.4% while the response rate for preceptees was 33%. Herzberg's theory served as the conceptual framework. Three baccalaureate schools of nursing in Atlantic Canada comprised the setting. Analysis of data included frequencies, percentages, t-tests, and Pearson's product-moment correlation coefficient. Findings indicate that preceptors and preceptees differ significantly regarding aspects of their job, and their job in general. They also differ significantly in their rating of how often preceptees perform the planning/evaluation components of their care. A positive significant relationship exists between preceptee job satisfaction and clinical performance. No relationship was found to exist between preceptor job satisfaction and preceptee clinical performance. Additionally, in view of the limitations of the study (small sample, low response) limited conclusions can be drawn from the study.

Canada↗
PubMed1998

Hidden Markov models for detecting remote protein homologies.

MOTIVATION: A new hidden Markov model method (SAM-T98) for finding remote homologs of protein sequences is described and evaluated. The method begins with a single target sequence and iteratively builds a hidden Markov model (HMM) from the sequence and homologs found using the HMM for database search. SAM-T98 is also used to construct model libraries automatically from sequences in structural databases. METHODS: We evaluate the SAM-T98 method with four datasets. Three of the test sets are fold-recognition tests, where the correct answers are determined by structural similarity. The fourth uses a curated database. The method is compared against WU-BLASTP and against DOUBLE-BLAST, a two-step method similar to ISS, but using BLAST instead of FASTA. RESULTS: SAM-T98 had the fewest errors in all tests-dramatically so for the fold-recognition tests. At the minimum-error point on the SCOP (Structural Classification of Proteins)-domains test, SAM-T98 got 880 true positives and 68 false positives, DOUBLE-BLAST got 533 true positives with 71 false positives, and WU-BLASTP got 353 true positives with 24 false positives. The method is optimized to recognize superfamilies, and would require parameter adjustment to be used to find family or fold relationships. One key to the performance of the HMM method is a new score-normalization technique that compares the score to the score with a reversed model rather than to a uniform null model. AVAILABILITY: A World Wide Web server, as well as information on obtaining the Sequence Alignment and Modeling (SAM) software suite, can be found at http://www.cse.ucsc.edu/research/compbi o/ CONTACT: karplus@cse.ucsc.edu; http://www.cse.ucsc.edu/karplus

Algorithms↗
PubMed1998

Factors leading to a strike vote and strategies for reestablishing relationships.

An extremely difficult contract negotiation between a collective bargaining unit and a hospital resulted in a vote to strike by the nursing staff before reaching a final agreement. The authors describe the factors that led up to the strike vote. Realistic yet optimistic strategies for developing a working relationship with the bargaining unit leadership and the nursing staff are described.

Boston↗
PubMed1998

Restoring homeostasis in a residential care facility through behaviour modification.

A verbally aggressive, 32-year-old male with a traumatic brain injury was admitted to a unit in an aged care facility for residential care. The homeostasis of the unit was disrupted by the resident's verbal aggression and other inappropriate behaviours. With the guidance of a neuropsychologist, nursing staff were able to use behaviour modification to successfully replace the disruptive behaviours with more socially appropriate ones. A series of positive rewards was implemented in response to socially appropriate behaviour, whilst inappropriate behaviours received a negative reward. Several disruptive behaviours were affected by the single treatment implemented. This interdependence of targeted behaviours was viewed as a clinical advantage, as it served to provide a more rapid restoration of homeostasis to the unit. The use of a single-subject, multiple baseline design in this case study demonstrates that disruptive behaviours may be reversible.

Adult↗
PubMed1998

Cardiovascular, endocrine, and body fluid-electrolyte responses to salt loading in mRen-2 transgenic rats.

We previously demonstrated that mRen-2 transgenic [Tg(+)] rats are sensitive to chronic high NaCl intake, showing increased arterial pressure and vasopressin (VP) secretion. In this study, we determined the effect of a chronic osmotic challenge, 4 days of drinking 2% NaCl, on direct arterial blood pressure, heart rate, fluid-electrolyte balance, circadian rhythm of mean arterial pressure (MAP), and changes in plasma VP and catecholamines. Under baseline conditions, male Tg(+) rats showed a significant shift in the peak in circadian MAP into the light portion of the day-night cycle. Substitution of 2% NaCl for drinking water caused a rapid increase in MAP, 20 +/- 5 mmHg in Tg(+) rats within 6 h. Whereas the amplitude of circadian MAP fluctuations increased in salt-loaded Tg(+) rats, there was no significant change in the circadian timing of peak MAP with salt loading. Tg(+) rats showed exaggerated osmotic-induced increases in plasma VP, norepinephrine (NE), and epinephrine (Epi) compared with Tg(-) rats. Plasma NE and Epi were increased two- and fourfold, respectively, in the hypertensive rats with no significant change in the Tg(-) rats. Intravenous administration of a VP antagonist did not alter arterial pressure in either Tg(+) or Tg(-) rats. Tg(+) and Tg(-) rats showed a positive sodium balance with no significant difference observed between the groups. Tg(+) rats showed a significant increase in salt consumption, plasma sodium, osmolality, and hematocrit, accompanied by a negative water balance. We conclude that Tg(+) rats are sensitive to acute and chronic osmotic stimuli in terms of blood pressure, fluid-electrolyte balance, and plasma VP and catecholamines. Whereas elevated plasma VP does not contribute to the hypertensive response, increased sympathetic drive may mediate the salt-induced blood pressure changes in this model.

Animals↗
PubMed1997

Predicting protein structure using hidden Markov models.

We discuss how methods based on hidden Markov models performed in the fold-recognition section of the CASP2 experiment. Hidden Markov models were built for a representative set of just over 1,000 structures from the Protein Data Bank (PDB). Each CASP2 target sequence was scored against this library of HMMs. In addition, an HMM was built for each of the target sequences and all of the sequences in PDB were scored against that target model, with a good score on both methods indicating a high probability that the target sequence is homologous to the structure. The method worked well in comparison to other methods used at CASP2 for targets of moderate difficulty, where the closest structure in PDB could be aligned to the target with at least 15% residue identity.

Markov Chains↗
PubMed1997

Alterations in gene expression associated with primary demyelination and remyelination in the peripheral nervous system.

Primary demyelination is an important component of a number of human diseases and toxic neuropathies. Animal models of primary demyelination are useful for isolating processes involved in myelin breakdown and remyelination because the complicating events associated with axonal degeneration and regeneration are not present. The tellurium neuropathy model has proven especially useful in this respect. Tellurium specifically blocks synthesis of cholesterol, a major component of PNS myelin. The resulting cholesterol deficit in myelin-producing Schwann cells rapidly leads to sychronous primary demyelination of the sciatic nerve, which is followed by rapid synchronous remyelination when tellurium exposure is discontinued. Known alterations in gene expression for myelin proteins and for other proteins involved in the sequence of events associated with demyelination and subsequent remyelination in the PNS are reviewed, and new data regarding gene expression changes during tellurium neuropathy are presented and discussed.

Animals↗
PubMed1997

Scoring hidden Markov models.

MOTIVATION: Statistical sequence comparison techniques, such as hidden Markov models and generalized profiles, calculate the probability that a sequence was generated by a given model. Log-odds scoring is a means of evaluating this probability by comparing it to a null hypothesis, usually a simpler statistical model intended to represent the universe of sequences as a whole, rather than the group of interest. Such scoring leads to two immediate questions: what should the null model be, and what threshold of log-odds score should be deemed a match to the model. RESULTS: This paper analyses these two issues experimentally. Within the context of the Sequence Alignment and Modeling software suite (SAM), we consider a variety of null models and suitable thresholds. Additionally, we consider HMMer's log-odds scoring and SAM's original Z-scoring method. Among the null model choices, a simple looping null model that emits characters according to the geometric mean of the character probabilities in the columns modeled by the hidden Markov model (HMM) performs well or best across all four discrimination experiments.

Algorithms↗
PubMed1995

Oxytocin antisense reduces salt intake in the baroreceptor-denervated rat.

Experiments were performed to evaluate the role of central oxytocin (OT) in the inhibition of salt intake produced by sinoartic denervation (SAD). The effect of OT antisense treatment on 24 h intake of 2% NaCl in SAD and sham-operated (SO) rats was determined. PVN injection of unmodified antisense oligodeoxynucleotides (ODNs) to OT mRNA decreased intake of 2% NaCl in SAD, but not SO rats. Salt consumption was 22 +/- 4 ml after the injection of control ODN as compared to 8 +/- 4 ml after the OT antisense injection (P < 0.05). SAD animals also demonstrated an increased plasma OT response to salt loading, an elevation from 3.2 +/- 0.7 to 6.9 +/- 0.8 pg/ml. In contrast, salt ingestion produced no significant change in plasma OT in the SO group. The increased endocrine response in the SADs occurred even though salt intake was lower in this group. There were no group differences in plasma electrolytes or posterior pituitary OT content. Results show that OT antisense specifically inhibits salt intake in the denervated rat, suggesting that the central oxytocinergic axis stimulates sodium drive in this experimental model.

Animals↗
PubMed1994

Selecting clinical preceptors for basic baccalaureate nursing students: a critical issue in clinical teaching.

The concept of preceptorship in baccalaureate nursing education continues to be endorsed as a viable alternative clinical teaching strategy. However there remains a dearth of research to substantiate many of those benefits vis-à-vis preceptor, preceptee and ultimately the health care consumer. Moreover, there are minimal substantive data regarding the criteria which are required for the actual selection of the clinical preceptor. Not infrequently, preceptors are selected primarily for their availability during the clinical placement of students. As a result, baccalaureate nursing students are being preceptored by staff nurses with little or no preparation for assuming a role in which they are expected to promote the principles and ideology of baccalaureate nursing education. Is this fair to the preceptor, preceptee and the client? Can it be said that the nursing faculty, in promoting such a process, are in fact promoting the status quo?

Clinical Competence↗
PubMed1993

Site-specific effects of intracerebral injections of three neurokinins (neurokinin A, neurokinin K, and neurokinin gamma) on the expression of male rat sexual behavior.

Accumulating evidence indicates that neurokinins play a role in the neural regulation of male rat copulatory behavior. We have previously reported that injections of the neurokinin substance P into the medial preoptic nucleus facilitated male rat copulatory behavior. Recently, a number of other neurokinins, neurokinin K (neuropeptide K), neurokinin A (substance K), and neurokinin gamma (derived from the same gene as substance P), have been identified in the mammalian CNS. Therefore, in a series of experiments we examined the effects on male copulatory behavior following bilateral injections of different doses of neurokinin K (NkK), neurokinin A (NkA), or neurokinin gamma (Nk gamma) into the medial preoptic area (MPOA), bed nucleus of the stria terminalis (BnST), or the caudate/putamen. Bilateral injections of NkK into the MPOA or BnST inhibited the expression of male copulatory behavior. The most marked effect was seen following bilateral injections of 0.25 and 0.52 nmol of NkK into the MPOA and the BnST. These injections produced a dramatic suppression of copulatory behavior in previously sexually vigorous male rats when compared to control injections. In contrast, bilateral injections of three different doses of NkA into the MPOA failed to affect any parameter of male copulatory behavior. Bilateral injections of 0.431 nmol of Nk gamma into the MPOA failed to affect the expression of copulatory behavior, but significantly delayed its initiation when compared to controls. Bilateral injections of 0.251 nmol of NkK into the caudate/putamen had no significant effect on copulatory behavior in sexually vigorous male rats when compared to control injections. The results of the present study provide further support for a role of neurokinins in the regulation of copulatory behavior in male rat. Taken together, these results suggest that the effects of neurokinins upon the expression of male copulatory behavior are site specific for brain regions in the sexually dimorphic vomeronasal pathway which includes the MeA, BnST, and MPOA.

Amygdala↗
PubMed1993

Hospital response to psychosocial needs of AIDS inpatients.

Compassionate care for HIV-infected persons requires response to psychosocial needs. With no new external funding, Women's College Hospital, a 270-bed urban teaching hospital, provided effective psychosocial services for HIV-infected inpatients by developing a comprehensive policy, educating staff, organizing existing services into a psychosocial support team to provide crisis intervention, and developing liaisons with community AIDS organizations. A retrospective chart review of epidemiologic and psychosocial patient data was carried out for 59 HIV inpatients (58 men, 1 woman) admitted 1987-89. Of the cohort, 91% indicated homosexual contact as the only risk factor. A psychosocial support team contacted 90% of these inpatients. One third (36%) of the patients designated as next of kin individuals who were not legally or biologically related. Approximately 25%-30% made active arrangements for impending death, e.g. wills and funeral plans. Thirteen patients, 22%, died in hospital, and three, 5%, on first admission. Experience showed that psychosocial interventions that focus on human dignity and quality of life, normally seen as elements of palliative care, are critically important from the earliest stages of HIV disease and should not be reserved only for those who are terminally ill.

Acquired Immunodeficiency Syndrome↗