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P Stafford

Publications and source records attributed to P Stafford.

At least 19 recordsLinked to original sources
PubMed2006

A murine model for cerebral toxocariasis: characterization of host susceptibility and behaviour.

Toxocara canis, the parasitic roundworm of dogs, can infect a number of paratenic hosts, such as mice and humans, due to the widespread dissemination of its ova in the environment. In these paratenic hosts, larvae have been shown to exhibit a predilection for the central nervous system, resulting in an increasing number of parasites migrating to the brain as infection progresses. In an initial experiment, we investigated the differential brain involvement of T. canis in 7 strains of inbred mice, and chose 2 strains, susceptible (BALB/c) and resistant (NIH) to cerebral infection. In a second experiment, both strains were investigated in terms of course of migration, larval accumulation, and behavioural response to T. canis infection. Results revealed that infected BALB/c mice took significantly longer to drink from a water source (following a period of deprivation), compared with control mice, indicating some degree of memory impairment. Cerebral larval recoveries from both strains of mice demonstrated variation between the two experiments, suggesting that larval burdens may not be a reliable indicator of susceptibility or resistance to T. canis infection. The percentage of total recovered larvae in each organ may be a better representation of larval distribution. Our model system may provide insights into the impact of chronic geohelminth infection on cognitive development.

Analysis of Variance↗
PubMed2005

The development of a mouse model to explore resistance and susceptibility to early Ascaris suum infection.

Ascaris suum and Ascaris lumbricoides exhibit an over-dispersed frequency distribution in their host populations in both the adult and larval stages. The impact of host factors on this observed distribution is still poorly understood and difficult to investigate in the natural host populations. The use of a mouse model has been supported by the observations that the larval migratory pattern, in this host, mimics the pattern observed in the pig. We explored the extrinsic factors that might affect the quantitative recovery of larvae during this migration in order to standardize a model system facilitating accurate future assessment of host genetic variation on this phase of the infection. In Exp. 1 larvae accumulated in the livers of both C57BL/6j and BALB/c mice up to and including days 4-5 p.i. and then declined in both strains until day 9. Loss of larvae from the livers corresponded to arrival in the lungs and maximum accumulation on day 7 p.i. but recovery was considerably higher in C57BL/6j mice. It was concluded that day 7 recoveries gave the best indication of relative resistance/susceptibility to this parasite. In Exp. 2 A/J, BALB/c, CBA/Ca, C57BL/6j, C3H/HeN, DBA/2, NIH, SJL, and SWR mice were compared. C57BL/6j mice were identified as the most susceptible strain and CBA/Ca mice as having the most contrasting phenotype, but with a similar kinetic pattern of migration. Finally, in Exp. 3, a strong positive correlation between the size of the inoculum and the mean worm recovery from the lungs was found in CBA/Ca and C57BL/6j mice, but the difference between these strains was highly consistent, 66.6-80%, regardless of the initial dose. These results demonstrate that, using our protocols for infection and recovery, between-experiment variation in A. suum worm burdens is minimal, and that C57BL/6j mice are highly susceptible to infection compared to other strains. The mechanistic basis of this susceptibility in relation to the resistance of other strains is unknown, but the possibilities are reviewed.

Analysis of Variance↗
PubMed2001

The influence of inoculum size and time post-infection on the number and position of Toxocara canis larvae recovered from the brains of outbred CD1 mice.

Outbred CD1 mice were administered doses of 1000 and 3000 Toxocara canis eggs and postmortem took place on days 7, 42 and 120 post-infection. Mice were killed by cervical dislocation and brains were sagitally bisected and fixed in 10% neutral buffered formalin prior to histological preparation and examination. The number of T. canis larvae were counted per brain and per section and the number of larvae cited for the first time per section were also recorded. These observations were compared by dose administered and by day of postmortem. The total number of larvae per brain and per section was higher for the 3000 dose compared to the 1000 dose. A different pattern emerged for the number of larvae observed in the brain over the three postmortem days depending upon the dose received. For the 1000 dose larval numbers increase from day 7 to day 120 whereas for the 3000 dose the opposite trend occurs. Larvae were assigned to one of five regions in the brain - the telencephalon, diencephalon, cerebellum, medulla, pons and brain stem and the olfactory bulb. Larvae did not show a random distribution in the brain. The majority of larvae were recorded from the telencephalon and the cerebellum. The percentage of sections with larvae in them is higher for the 3000 dose compared to the 1000 dose for all regions of the brain. For the majority of regions, the percentage of sections with larvae in them increases between day 7 and 42 and then decreases by day 120 and this is most pronounced for the cerebellum. For the telencephalon and diencephalon only, more larvae were detected on the right hand side of the brain compared to the left hand side. Statistical analysis revealed that dose and brain region are significant factors which influence the number of larvae observed in histological sections of the brain but day post-infection is not.

Analysis of Variance↗
PubMed2000

Sequence and phylogenetic analysis of squid myosin-V: a vesicle motor in nerve cells.

We have shown that vesicles in the axoplasm of the squid giant axon move on actin filaments and that movement is inhibited by myosin V-specific antibodies [Tabb et al., 1998]. In the study reported in this article, experiments were performed to clone and sequence the cDNA for squid brain myosin V. Five proteolytic fragments of purified squid brain myosin V were analyzed by direct protein sequencing [Tabb et al., 1998]. Based on this sequence information, degenerate primers were constructed and used to isolate cDNA clones by PCR. Five clones, representing overlapping segments of the gene, were sequenced. The sequence data and the previous biochemical characterization of the molecule support the classification of this vesicle-associated myosin as a member of the class V myosins. Motif analysis of the head, neck, and tail domains revealed that squid MyoV has consensus sequences for all the motifs found in vertebrate members of the myosin V family of motor proteins. A phylogenetic tree was constructed from a sequence alignment by the neighbor-joining method, using Megalign (DNAStar, Madison, WI); the resulting phylogenetic tree showed that squid MyoV is more closely related to vertebrate MyoV (mouse dilute, chicken dilute, rat myr6, and human myo5a) than Drosophila and yeast (myo2, and myo4) myosins V. These new data on the phylogenetic relationships of squid myosin V to vertebrate myosin V strengthens the argument that myosin V functions as a vesicle motor in vertebrate neurons.

Amino Acid Motifs↗
PubMed2000

The effect of screw insertion site and unused drill holes on stability and mode of failure after fixation of basicervical femoral neck fracture.

The intent of this biomechanical study is to characterize the effect of unused drill holes and cannulated screw insertion site on the fixation stability and mode of failure after fixation of basicervical femoral neck fractures. Fourteen matched pairs of embalmed human cadaver femora were sorted into four groups according to the level of screw insertion along the lateral cortex. Screws inserted at higher positions along the lateral cortex afforded higher rigidity, thus decreasing the amount of motion at the fracture site. In addition, higher insertion positions reduced the rate of permanent displacement, thus better maintaining reduction. Although all specimens failed at the neck, post-failure inspection revealed upward translation of the inferior screw head when inserted 20 mm below the lesser trochanter. Unused drill holes and guidepin holes had no observed affect on stability or failure mode.

Biomechanical Phenomena↗
PubMed1999

Rat8p/Dbp5p is a shuttling transport factor that interacts with Rat7p/Nup159p and Gle1p and suppresses the mRNA export defect of xpo1-1 cells.

In a screen for temperature-sensitive mutants of Saccharomyces cerevisiae defective for mRNA export, we previously identified the essential DEAD-box protein Dbp5p/Rat8p and the nucleoporin Rat7p/Nup159p. Both are essential for mRNA export. Here we report that Dbp5p and Rat7p interact through their Nterminal domains. Deletion of this portion of Rat7p (Rat7pDeltaN) results in strong defects in mRNA export and eliminates association of Dbp5p with nuclear pores. Overexpression of Dbp5p completely suppressed the growth and mRNA export defects of rat7DeltaN cells and resulted in weaker suppression in cells carrying rat7-1 or the rss1-37 allele of GLE1. Dbp5p interacts with Gle1p independently of the N-terminus of Dbp5p. Dbp5p shuttles between nucleus and cytoplasm in an Xpo1p-dependent manner. It accumulates in nuclei of xpo1-1 cells and in cells with mutations affecting Mex67p (mex67-5), Gsp1p (Ran) or Ran effectors. Overexpression of Dbp5p prevents nuclear accumulation of mRNA in xpo1-1 cells, but does not restore growth, suggesting that the RNA export defect of xpo1-1 cells may be indirect. In a screen for high-copy suppressors of the rat8-2 allele of DBP5, we identified YMR255w, now called GFD1. Gfd1p is not essential, interacts with Gle1p and Rip1p/Nup42p, and is found in the cytoplasm and at the nuclear rim.

Adenosine Triphosphatases↗
PubMed1995

Frequency analysis of the P wave: comparative techniques.

Frequency domain analysis of the signal-averaged P wave (SAPW) may provide additional information over time domain analysis in patients with paroxysmal atrial fibrillation (PAF), but an optimum method has not yet been defined. We compared two different approaches using SAPW and test signals. We analyzed the frequency spectrum of the entire P wave (method A) or of only its terminal 100 msec (method B) using SAPW from 24 patients with idiopathic PAF and 34 normal controls. Absolute powers in frequency bands above 20, 30, 40, 60, and 80Hz (P20, P30, P40, P60, and P80) and power ratios about these frequencies (PR20, PR30, PR40, PR60, and PR80) were calculated. Patients had greater P30, P60, and P80 using method A (P30: 28.6 [+/- 2.2] vs 22.8 [+/- 1.6] microV2.s; P = 0.04; P60: 4.7 [+/- 0.5] vs 3.4 [+/- 0.3] microV2.s; P = 0.03; P80: 1.9 [+/- 0.2] vs 1.3 [+/- 0.09] microV2.s; P = 0.01) but differences were smaller with method B. Moving the P wave endpoint 10 msec into the P wave had no effect on frequency domain parameters using method A but produced important changes using method B. Both methods were also applied to test signals of different durations but equal powers and power ratios. Method A gave predicted values for power and PR40 at all signal durations, but method B produced variable results. Frequency domain analysis of the SAPW shows significant increases in P wave energy in patients with PAF compared to controls. Analysis of the entire P wave is influenced less by signal duration and variations of the P wave endpoint than analysis of the terminal P wave alone and may define patient and control populations more precisely.

Algorithms↗
PubMed1995

Signal-averaged electrocardiography of the sinus and paced P wave in sinus node disease.

The detection of paroxysmal atrial fibrillation (AF) in patients requiring a permanent pacemaker for sinus node disease may influence the choice of both pacemaker and programmed mode. While signal-averaged ECG of the P wave (SAEP) during sinus rhythm may detect patients with paroxysmal AF, the value of SAEP in the presence of sinus node disease is unknown. We therefore evaluated SAEP in patients with sinus node disease during sinus rhythm and atrial pacing. We investigated 10 patients with sinus node disease alone (SND), 10 with sinus node disease and paroxysmal AF (SND-PAF), and 20 normal controls (NC) using a P wave specific, signal-averaging system. In sinus rhythm, duration and energy were greater in SND-PAF than in SND and NC (mean [SEM] duration: 153 [4] msec, 140 [4] msec, and 134 [2] msec, P < 0.001; energy from 20-150 Hz: 76 [18] muV2.sec, 48 [7] muV2.sec, and 36 [3] muV2.sec, P = 0.006). Atrial pacing in SND-PAF produced an 11% prolongation of atrial activation but little further abnormality in P wave characteristics. In SND, atrial pacing caused a 20% prolongation of the P wave and increased P wave energy to a greater extent than in SND-PAF. We conclude that in patients with SND, atrial activation appears similar to normal controls during sinus rhythm but changes significantly on pacing. In patients with SND-PAF, atrial activation is abnormal during sinus rhythm with little further change when the atrium is paced. SAEP may be useful in detecting a predisposition to paroxysmal AF in the presence of sinus node disease and might help optimize pacemaker prescription.

Adult↗
PubMed1990

Influence of grade, histologic subtype, and timing of radiotherapy on outcome among patients with stage II carcinoma of the endometrium.

In 1988, the Federation of International Gynecologic Oncologists (FIGO) adopted a new staging system mandating preradiotherapy surgical staging in endometrial cancer. To evaluate the potential impact of this recommendation on patients with cervical involvement (stage II), an analysis of 184 consecutive patients with clinical or pathologic stage II carcinoma of the endometrium treated with definitive intent at three institutions was performed. Median follow-up time was 5.7 years. Treatment consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy with preoperative radiation therapy (RT) (54%), postoperative RT (37%), or both (1%); definitive RT (7%); or radical hysterectomy (1%). The median total RT dose for combined intracavitary and external beam or either alone was 70.6 Gy with a range of 32.4-105.0 Gy. The overall 5-year survival rate and disease-free survival (DFS) rate at 5 years were 70 and 79%, respectively. Of patients treated with surgery and adjuvant radiation, 13% (22/168) had infield pelvic failure (PF) and 18% (31/168) had distant metastases (DM). Patterns of failure in patients receiving preoperative and postoperative radiotherapy are presented. Univariate analysis of pretreatment and treatment factors, including histology, grade, clinical stage, extent of cervical involvement, and timing of adjuvant radiation, revealed histology and grade to be significant predictors of DFS, PF, and DM. Clinical stage was a significant predictor of DFS only in univariate analysis. Multivariate analysis found only histology (P less than 0.001) and grade (P = 0.002) to be predictors of DFS. From this review, we conclude that histology and grade are independent predictors of DFS, and more aggressive treatment should be directed at patients with stage II endometrial cancer found to have high grade adenocarcinoma or papillary serous/clear cell histologic variants. The timing of radiotherapy was not an independent predictor of outcome; therefore, preradiotherapy surgical staging should not impact on DFS and should provide surgicopathologic information to tailor treatment and predict prognosis. The FIGO clinical staging system used in this analysis was not an independent predictor of outcome, and future multivariate analyses will be necessary to test the predictive value on outcome of the new 1988 FIGO surgical staging.

Female↗
PubMed1989

Microdosimetry of a 42 MeV therapy neutron beam.

Radiation quality of fast neutron therapy beams can change with depth. For a neutron beam generated by p----Be, the primary effect is a "hardening" of the neutron beam produced by the scattering of slow neutron components. A 42 MeV neutron therapy beam was investigated using microdosimetric techniques. We report measurements of dose mean and saturation-corrected lineal energy in water phantom at build-up depth, 5, 15, and 30 cm, and show representative logarithmic dose distributions in lineal energy. RBE is also calculated using assumptions based on the Theory of Dual Radiation Action and presented as a function of dose and depth.

Humans↗
PubMedDate not supplied

Effects of plate location and selection on the stability of midshaft clavicle osteotomies: a biomechanical study.

Operative fixation of midshaft clavicle fractures is controversial with few biomechanical data to assist surgical decision making. The purpose of this 2-phase biomechanical investigation is to report on the effects of plate location and selection on the stability of midshaft clavicle fractures. Thirty matched pairs of human adult formalin-fixed clavicles were used. In the first phase, in which a 3.5-mm reconstruction plate and simulated midshaft transverse clavicle osteotomies were used, we observed the effect of superior plate placement compared with anterior placement on fracture rigidity, construct stiffness, and strength. In the second phase, in which simulated midshaft oblique clavicle osteotomies were repaired on the superior aspect, we compared the fracture rigidity, construct stiffness, and strength of the 3.5-mm reconstruction, 3.5-mm limited contact dynamic compression (LCDC), and 2.7-mm dynamic compression (DC) plates. Intact clavicles were prepared, potted, and tested for axial and torsional stiffness in an Instron test frame equipped with gimbaled fixtures. Clavicles were band-sawed to simulate an osteotomy, repaired, re-mounted on the test frame with shear and opening extensometers placed across the osteotomy site, and then tested to observe axial and torsional fracture rigidity and stiffness. Constructs were then loaded to failure in compression. First-order regressions were used to estimate fracture rigidity (in kilonewtons per millimeter)and retained construct stiffness (in kilonewtons per millimeter), whereas the maximum applied compressive load at collapse or gross deformation determined the failure load. Values for the comparisongroups were tested for significance at the 95% confidence level. In the first phase we found that constructs plated at the superior aspect of the clavicle exhibited significantly greater fracture rigidity and mean retained stiffness than the anterior location (P <.05). In the second phase we found that the torsional fracture rigidity of LCDC-plated constructs significantly exceeded that of the reconstruction and DC plates (P <.05), whereas the axial fracture rigidity of the LCDC-plated constructs significantly exceeded that of the reconstruction plate (P <.05). In retained stiffness the performance of the LCDC-plated constructs significantly exceeded that of the DC plate in torsion (P <.05), whereas in load to failure the LCDC plate withstood significantly more compressive load than the reconstruction plate (P <.05). We concluded that clavicles plated at the superior aspect exhibit significantly greater biomechanical stability than those plated at the anterior aspect. Furthermore, we concluded that the LCDC plate offers significantly greater biomechanical stability than the reconstruction and DC plates.

Aged↗