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Biomedical subjects

D L Fisher

Publications and source records attributed to D L Fisher.

At least 19 recordsLinked to original sources

Hsp90 is required for c-Mos activation and biphasic MAP kinase activation in Xenopus oocytes.

During Xenopus oocyte maturation, the Mos protein kinase is synthesized and activates the MAP kinase cascade. In this report, we demonstrate that the synthesis and activation of Mos are two separable processes. We find that Hsp90 function is required for activation and phosphorylation of Mos and full activation of the MAP kinase cascade. Once Mos is activated, Hsp90 function is no longer required. We show that Mos interacts with both Hsp90 and Hsp70, and that there is an inverse relationship between association of Mos with these two chaperones. We propose that Mos protein kinase is activated by a novel mechanism involving sequential association with Hsp70 and Hsp90 as well as phosphorylation. We also present evidence for a two-phase activation of MAP kinase in Xenopus oocytes.

Animals↗

Evaluation of graft patency during minimally invasive coronary artery bypass grafting with Doppler flow analysis.

BACKGROUND: An objective method for determining intraoperative graft patency is an essential part of minimally invasive direct coronary artery bypass. This study compares angiography and Doppler methods for graft analysis during minimally invasive direct coronary artery bypass and presents long-term outcome in a cohort of patients. METHODS: Between March and October 1997, 35 patients had elective minimally invasive direct coronary artery bypass procedures in which the left internal mammary artery was anastomosed to the left anterior descending coronary artery. Immediate graft patency was determined with intraoperative angiography using selective injection of the left internal mammary artery from a femoral approach and with Doppler flow analysis using a 1-mm, 20-MHz Doppler probe placed directly on the graft. RESULTS: There was immediate perfect patency with brisk flow in 91% of patients (32 of 35). A normal Doppler study, defined as a diastolic predominant pattern with a diastolic flow velocity of greater than 15 cm/second, was found in all patients with normal angiograms. All patients with abnormal angiograms also had abnormal Doppler flow. Thus, Doppler analysis was 100% accurate for confirming graft patency and for detecting failed grafts. All abnormal grafts were successfully revised, which allowed 100% early patency. Operative mortality was 2.8% (1 of 35) and there have been no late deaths at a follow-up of more than 2 years. One patient required angioplasty of the anastomosis (1 of 34, 2.9%), but none have required subsequent surgical intervention. CONCLUSIONS: Objective analysis of graft flow in the operating room is necessary to achieve 100% early graft patency with minimally invasive direct coronary artery bypass operations. Doppler analysis is the preferred initial method, because it is safe, accurate, and rapid.

Adult↗

The framing of drivers' route choices when travel time information is provided under varying degrees of cognitive load.

In two experiments, participants chose between staying on a main route with a certain travel time and diverting to an alternative route that could take a range of travel times. In the first experiment, travel time information was displayed on a sheet of paper to participants seated at a desk. In the second experiment, the same information was displayed in a virtual environment through which participants drove. Overall, participants were risk-averse when the average travel time along the alternative route was shorter than the certain travel time of the main route but risk-seeking when the average travel time of the alternative route was longer than the certain travel time along the main route. In the second experiment, in which cognitive load was higher, participants simplified their decision-making strategies. A simple probabilistic model describes the risk-taking behavior and the load effects. Actual or potential applications of this research include the development of efficient travel time information systems for drivers.

Adult↗

Dissociation of MAP kinase activation and MPF activation in hormone-stimulated maturation of Xenopus oocytes.

MAP kinase activation occurs during meiotic maturation of oocytes from all animals, but the requirement for MAP kinase activation in reinitiation of meiosis appears to vary between different classes. In particular, it has become accepted that MAP kinase activation is necessary for progesterone-stimulated meiotic maturation of Xenopus oocytes, while this is clearly not the case in other systems. In this paper, we demonstrate that MAP kinase activation in Xenopus oocytes is an early response to progesterone and can be temporally dissociated from MPF activation. We show that MAP kinase activation can be suppressed by treatment with geldanamycin or by overexpression of the MAP kinase phosphatase Pyst1. A transient and low-level early activation of MAP kinase increases the efficiency of cell cycle activation later on, when MAP kinase activity is no longer essential. Many oocytes can still undergo reinitiation of meiosis in the absence of active MAP kinase. Suppression of MAP kinase activation does not affect the formation or activation of Cdc2-cyclin B complexes, but reduces the level of active Cdc2 kinase. We discuss these findings in the context of a universal mechanism for meiotic maturation in oocytes throughout the animal kingdom.

Animals↗

A novel role for glycogen synthase kinase-3 in Xenopus development: maintenance of oocyte cell cycle arrest by a beta-catenin-independent mechanism.

We have examined the expression of glycogen synthase kinase-3beta in oocytes and early embryos of Xenopus and found that the protein is developmentally regulated. In resting oocytes, GSK-3beta is active and it is inactivated on maturation in response to progesterone. GSK-3beta inactivation is necessary and rate limiting for the cell cycle response to this hormone and the subsequent accumulation of beta-catenin. Overexpression of a dominant negative form of the kinase accelerates maturation, as does inactivation by expression of Xenopus Dishevelled or microinjection of an inactivating antibody. Cell cycle inhibition by GSK-3beta is not mediated by the level of beta-catenin or by a direct effect on either the MAP kinase pathway or translation of mos and cyclin B1. These data indicate a novel role for GSK-3beta in Xenopus development: in addition to controlling specification of the dorsoventral axis in embryos, it mediates cell cycle arrest in oocytes.

Animals↗

Reliability of magnetic resonance imaging in predicting disc material posterior to the posterior longitudinal ligament in the cervical spine. A prospective study.

STUDY DESIGN: This was a prospective study to evaluate the accuracy of magnetic resonance imaging in predicting the presence of disc material posterior to the posterior longitudinal ligament (PLL), compared with the accuracy of intraoperative visual and tactile examination of the PLL. OBJECTIVES: To determine the accuracy of magnetic resonance imaging in predicting the presence of disc material posterior to the PLL. SUMMARY OF BACKGROUND DATA: Whether removal of the disc to the PLL is sufficient when performing an anterior cervical discectomy and fusion or it is necessary to explore the spinal canal by taking down the PLL is controversial. METHODS: Fifty-four cervical levels were examined by magnetic resonance imaging before surgery to determine whether there was disc material posterior to the PLL. During surgery, the PLL was examined and probed for disruption. The ligament was taken down, and free fragments were identified and removed. RESULTS: Of 54 levels, 12 were correctly identified by magnetic resonance imaging as having disc material posterior to the PLL, and 26 were correctly identified as not having disc material posterior to the PLL. Surgery confirmed that at 26 levels there was disc material posterior to the PLL. Of these 26, 23 (88.5%) had visual or palpable disruption of the PLL. Magnetic resonance imaging failed to predict disc material posterior to the PLL in 14 of the cases in which its presence was confirmed during surgery. Magnetic resonance imaging had 46.2% sensitivity and 92.9% specificity rates. CONCLUSIONS: Because of low sensitivity, magnetic resonance imaging should be used cautiously for predicting free disc material posterior to the PLL. Visual or palpable examination of the PLL during surgery is more accurate for this prediction.

Cervical Vertebrae↗

The acute phase response in the Sudan plated lizard, Gerrhosaurus major.

The Sudan plated lizard (Gerrhosaurus major), previously reported to be an afebrile species, was utilized in a series of experiments to test for various aspects of the acute phase response. Treatment of individuals with the antibiotic Baytril resulted in a slight (0.5 degree C) but significant reduction in mean selected body temperature (MSBT), while treatment with saline did not lower MSBT. Nonantibiotic treatment individuals had depressed plasma iron levels (86.6 +/- 22.4 micrograms Fe 100 ml-1 plasma) and treatment with Baytril produced a significant increase in plasma iron concentration (186.8 +/- 19.5 micrograms Fe 100 ml-1 plasma). Necropsy of randomly selected individuals indicated that animals obtained from the commercial supplier had Aeromonas, Arthrobacter, Pseudomonas and Salmonella infections and antibiotic treatment eliminated these infections. The growth rate of Aeromonas sobria is reduced when the bacteria are grown at 32 degrees C and reduced iron concentration compared to 34.5 degrees C and low iron concentration, which suggests that a fever response may not be beneficial in reducing bacterial growth. Saline injected, bacteria injected and antibiotic injected Gerrhosaurus major have high plasma zinc concentrations compared to the previously studied febrile species, Dipsosaurus dorsalis. This difference suggests that zinc concentrations in afebrile species deserve further study.

Acute-Phase Reaction↗

Toward a model of eye movement control in reading.

The authors present several versions of a general model, titled the E-Z Reader model, of eye movement control in reading. The major goal of the modeling is to relate cognitive processing (specifically aspects of lexical access) to eye movements in reading. The earliest and simplest versions of the model (E-Z Readers 1 and 2) merely attempt to explain the total time spent on a word before moving forward (the gaze duration) and the probability of fixating a word; later versions (E-Z Readers 3-5) also attempt to explain the durations of individual fixations on individual words and the number of fixations on individual words. The final version (E-Z Reader 5) appears to be psychologically plausible and gives a good account of many phenomena in reading. It is also a good tool for analyzing eye movement data in reading. Limitations of the model and directions for future research are also discussed.

Attention↗

Visual search tasks: slowing of strategic and nonstrategic processes in the nonlexical domain.

Some investigators have argued that aging affects the slowing of processes in nonlexical tasks more than it does the slowing of processes in lexical tasks, but that within task domains, the slowing is identical. Other investigators have argued that even within nonlexical tasks there is differential slowing such that aging affects processing speed more in (nonlexical) coordinative tasks than it does in (nonlexical) sequential tasks. Perhaps, more finely still, there is a differential slowing in coordinative nonlexical tasks. Toward this end, latent models of general and process-specific slowing in coordinative nonlexical tasks were formulated for older adults. A visual search task was then used to test the two types of models. It was found that a latent model of process-specific slowing explained significantly more of the variability than a latent model of general slowing, indicating that there is a differential slowing of processes among coordinative tasks within the nonlexical domain. It was also discovered that the coordinative process most greatly affected was that of deciding to terminate the search when no target was present in the display, indicating together with other studies a possible difference in the slowing of strategic processes among both coordinative and sequential tasks within the nonlexical domain, but no difference in the slowing of nonstrategic processes.

Adult↗

Sound localization: information theory analysis.

Sound localization has been studied extensively. Curiously, although much is known about factors that affect errors, little is known about factors that influence response time. Three experiments were performed in an attempt to identify the separate influence of each of several different factors. All trials used a single broadband noise signal emanating from one of a subset of six loudspeakers equally spaced around the participant in the azimuthal plane. Both the size of the subset and the balance of relative probabilities from speaker to speaker were altered to evaluate the relationship between information content and the dependent variable, choice reaction time. Choice reaction time was found to be related to the information content of the sound stimulus in all cases. It was also found to be related to the presence of pairs of speakers that were symmetrically opposed in front of the behind the participant. Models of choice reaction time in a sound localization task have clear implications for practice. For example, they suggest that multiple auditory collision warnings may endanger drivers.

Adult↗

Improving nursing education classroom environments.

This study describes the first use of a classroom environment questionnaire with a class in nursing education. An instructor of nursing students monitored classes using such a questionnaire. The questionnaire used was the College and University Classroom Environment Inventory and it was used to obtain practical and useful information about the learning environment in two different classes. Collaborative changes were made in the classes to improve the classroom environment and consequently the learning situation. Any instructor of nursing students could use this same process with this instrument.

Adult↗

Minimizing fatigue during repetitive jobs: optimal work-rest schedules.

Twenty women were asked to generate forces using a dynamometer that were consistent with one of three different work-rest schedules (a low-, medium-, and high-force schedule). Each work-rest schedule consisted of 6 identical blocks of 10 work-rest cycles. Each of the 10 work-rest cycles lasted 1 min. The first work-rest cycle in each block consisted of a 6-s maximal voluntary contraction and a 54-s rest. The remaining 9 work-rest cycles in each block consisted of a submaximal contraction and a rest period. The desired force of the submaximal contraction, the length of this contraction, and the duration of the rest period remained constant within schedules but varied across schedules. The amount of physiological work was kept constant among schedules. The fatigue that developed in the medium-force schedule was significantly lower than that developed in either the low- or high-force schedule. A model was developed that predicted the amount of fatiguable strength at the beginning and end of each contraction of a work-rest cycle. When fit to the results from the experiment, the model explained 94% of the variance. The model can be used to predict the work-rest schedule that minimizes fatigue in a given repetitive job, thereby potentially increasing productivity and reducing the incidence of cumulative trauma disorders.

Adult↗

A single fission yeast mitotic cyclin B p34cdc2 kinase promotes both S-phase and mitosis in the absence of G1 cyclins.

Deletion of the fission yeast mitotic B-type cyclin gene cdc13 causes cells to undergo successive rounds of DNA replication. We have used a strain which expresses cdc13 conditionally to investigate re-replication. Activity of Start genes cdc2 and cdc10 is necessary and p34cdc2 kinase is active in re-replicating cells. We tested to see whether other cyclins were required for re-replication using cdc13delta. Further deletion of cig1 and puc1 had no effect, but deletion of cig2/cyc17 caused a severe delay in re-replication. Deletion of cig1 and cig2/cyc17 together abolished re-replication completely and cells arrested in G1. This, and analysis of the temperature sensitive cdc13-117 mutant, suggests that cdc13 can effectively substitute for the G1 cyclin activity of cig2/cyc17. We have characterized p56cdc13 activity and find evidence that in the absence of G1 cyclins, S-phase is delayed until the mitotic p34cdc2-p56cdc13 kinase is sufficiently active. These data suggest that a single oscillation of p34cdc2 kinase activity provided by a single B-type cyclin can promote ordered progression into both DNA replication and mitosis, and that the level of cyclin-dependent kinase activity may act as a master regulator dictating whether cells undergo S-phase or mitosis.

CDC2 Protein Kinase↗

Further validation of a quadruplex STR DNA typing system: a collaborative effort to identify victims of a mass disaster.

The relatively new, PCR-based technique of Short Tandem Repeat (STR) profiling has been used in the identification of the victims of a mass disaster. The analysis relied upon a recently developed multiplex reaction and the use of automated fluorescence technology to simulataneously analyse four tetrameric STR loci. The performance of the 'quadruplex' test was assessed by use of a collaborative study incorporating a blind trial and was demonstrated to be accurate, reliable and robust. Furthermore, the system proved to be highly successful despite the fact that many of the samples from the mass disaster scene were extremely degraded. The high success rate coupled with the discrimination power of the system enabled many severely decomposed human remains to be positively identified.

DNA↗

Improved expression of a hybrid Streptomyces clavuligerus cefE gene in Penicillium chrysogenum.

A hybrid cefE gene, encoding penicillin N expandase, was constructed by fusing the promoter sequences, Pcp, and terminator sequences, Pct from the Penicillium chrysogenum pcbC gene to the open reading frame (orf), cefEorf, from the Streptomyces clavuligerus cefE gene. The resulting hybrid gene, Pcp/cefE'orf/Pct, differed from a previously reported hybrid cefE gene contained on plasmid pPS65. The latter gene, Pcp/cefE'orf/Sct, contained the Pcp sequences fused to the S. clavuligerus cefE orf still attached to the S. clavuligerus terminator sequences, Sct. The new hybrid gene was transformed into P. chrysogenum on plasmid vector pRH6. Transformants were selected by phleomycin resistance conferred by a hybrid ble gene present on plasmid pRH6. The hybrid ble gene was formed by attaching Pcp sequences to the ble orf. Among transformants obtained with pRH6, one exhibited a 70-fold higher level of activity of penicillin N expandase than the best transformant previously obtained from a 10-fold larger population of pPS65 transformants. The penicillin N expandase activity in pRH6 transformant, 9EN-5-1, was fourfold higher than the activity in the S. clavuligerus strain used as the source of the cefE orf and 75% of the activity observed in an industrial strain of Cephalosporium acremonium. Sequencing of the junctions of the heterologous DNA in Pcp/cefEorf/Pct uncovered a modification of the cefE open reading frame introduced during construction of the hybrid gene; the modified open reading frame is designated cefE'orf.

Base Sequence↗

Brinley plots and theories of aging: the explicit, muddled, and implicit debates.

We evaluated the debates concerning Brinley plots and the associated theories of age-related slowing. We concluded that an explicit debate regarding a single-factor, general slowing model was no longer a debate as most, if not all, agree to the disconfirmation of that model. We address sources of confusion in the debates that have muddled the areas of genuine disagreement. When the confusion is lifted, the remaining debate centers, rightly, on evaluation of theories of aging. We show that Brinley plot analyses can lead to both falsely accepting and falsely rejecting theories of age-related slowing. Although plotting data most certainly can assist with the evaluation of cognitive theory, we argue that models of performance and learning must play a more central role in advancing theories of cognitive aging.

Adolescent↗

Short tandem repeat loci: application to forensic and human remains identification.

The short tandem repeat (STR) locus ACTBP2 (common name SE33) was analyzed for its potential use in forensic and human remains identification. PCR amplification conditions were determined, and an allele-specific ladder was generated so that discrete alleles could be scored. The allele frequency distributions were determined for both Caucasian and Black populations. The frequency data meets Hardy-Weinberg expectations, and the allele distributions were similar from one racial group to another and between ethnic groups. SE33 analysis was subsequently used to confirm the identification of human remains for the Office of the Armed Forces Medical Examiners.

Alleles↗

Repetitive motion disorders: the design of optimal rate-rest profiles.

Repetitive motion disorders of the upper extremities are the primary cause of lost time in hand-intensive industries. Typical remedies include the introduction of job aids and the redesign of the job. An alternative approach is considered here. Procedures are developed that can be used to determine the parameters of a job (e.g., the rate of work and the number and duration of the rest breaks) that minimize repetitive motion disorders and maximize productivity. It is shown that in theory the job parameters can be set so that one can achieve not only a decrease in repetitive motion disorders but also an increase in productivity. The application of the procedures to an actual manufacturing job requiring high-repetitive, high-force hand motions is discussed in detail.

Cumulative Trauma Disorders↗