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D Johnston

Publications and source records attributed to D Johnston.

At least 55 records · Page 3Linked to original sources
PubMed2000

Dendritic potassium channels in hippocampal pyramidal neurons.

Potassium channels located in the dendrites of hippocampal CA1 pyramidal neurons control the shape and amplitude of back-propagating action potentials, the amplitude of excitatory postsynaptic potentials and dendritic excitability. Non-uniform gradients in the distribution of potassium channels in the dendrites make the dendritic electrical properties markedly different from those found in the soma. For example, the influence of a fast, calcium-dependent potassium current on action potential repolarization is progressively reduced in the first 150 micrometer of the apical dendrites, so that action potentials recorded farther than 200 micrometer from the soma have no fast after-hyperpolarization and are wider than those in the soma. The peak amplitude of back-propagating action potentials is also progressively reduced in the dendrites because of the increasing density of a transient potassium channel with distance from the soma. The activation of this channel can be reduced by the activity of a number of protein kinases as well as by prior depolarization. The depolarization from excitatory postsynaptic potentials (EPSPs) can inactivate these A-type K+ channels and thus lead to an increase in the amplitude of dendritic action potentials, provided the EPSP and the action potentials occur within the appropriate time window. This time window could be in the order of 15 ms and may play a role in long-term potentiation induced by pairing EPSPs and back-propagating action potentials.

Action Potentials↗
PubMed2000

Weak Gravitational Lensing by the Nearby Cluster Abell 3667.

We present two weak lensing reconstructions of the nearby (zcl=0.055) merging cluster Abell 3667, based on observations taken approximately 1 yr apart under different seeing conditions. This is the lowest redshift cluster with a weak lensing mass reconstruction to date. The reproducibility of features in the two mass maps demonstrates that weak lensing studies of low-redshift clusters are feasible. These data constitute the first results from an X-ray luminosity-selected weak lensing survey of 19 low-redshift (z<0.1) southern clusters.

Journal Article↗
PubMed2000

Construction and characterization of a Schistosoma mansoni bacterial artificial chromosome library.

A bacterial artificial chromosome (BAC) library has been established from genomic DNA isolated from the trematode parasite of human, Schistosoma mansoni. This library consists of more than 21,000 recombinant clones carrying inserts in the pBeloBAC11 vector. The mean insert size was 100 kb, representing an approximate 7.95-fold genome coverage. Library screening with eight chromosome-specific or single-copy gene probes yielded between 1 and 9 positive clones, and none of those tested was absent from the library. End sequences were obtained for 93 randomly selected clones, and 37 showed sequence identity to S. mansoni sequences (ESTs, genes, or repetitive sequences). A preliminary analysis by fluorescence in situ hybridization localized 8 clones on schistosome chromosomes 1 (2 clones), 2, 3, 5, Z, and W (3 clones). This library provides a new resource for the physical mapping and sequencing of the genome of this important human pathogen.

Animals↗
PubMed2000

Nonsyndromic cleft lip and palate is not associated with cancer or other birth defects.

Nonsyndromic cleft lip with or without cleft palate (NSCLP) is one of the most common human malformations with an average prevalence of 1 in 1,000 live births. The cause(s) of NSCLP remain unclear as the relative roles of genes, of the environment, and/or of chance alone are unknown. The purpose of this study was to evaluate the potential role of environmental factors in the cause of NSCLP, to determine if other birth defects aggregate in families with at least one individual affected with NSCLP, and to investigate the frequency of cancer in the first- and second-degree relatives of NSCLP index-cases. Included in this study were 196 index-cases and their families. Information pertaining to environmental factors and pedigree information was obtained on each family. Analysis showed that no single environmental factor could explain the occurrence of NSCLP in this population. The frequency of other birth defects in these families was 1.2%, which is not increased over that in the general population. One hundred seven cancers were reported in 72 of the 196 families included in the study. The frequency of cancer was not significantly increased in the first- or second-degree relatives of the NSCLP index cases or in those families with a positive family history of NSCLP. No childhood or adult cancers were reported in any of the 196 NSCLP index cases.

Abnormalities, Multiple↗
PubMed2000

Spectroscopic analysis of neural activity in brain: increased oxygen consumption following activation of barrel cortex.

This research investigates the hemodynamic response to stimulation of the barrel cortex in anaesthetized rats using optical imaging and spectroscopy (Bonhoeffer and Grinvald, 1996; Malonek and Grinvald, 1996; Mayhew et al., 1999). A slit spectrograph was used to collect spectral image data sequences. These were analyzed using an algorithm that corrects for the wavelength dependency in the optical path lengths produced by the light scattering properties of tissue. The analysis produced the changes in the oxy- and deoxygenation of hemoglobin following stimulation. Two methods of stimulation were used. One method mechanically vibrated a single whisker, the other electrically stimulated the whisker pad. The electrical stimulation intensity varied from 0.4 to 1.6 mA. The hemodynamic responses to stimulation increased as a function of intensity. At 0.4 mA they were commensurate with those from the mechanical stimulation; however, the responses at the higher levels were greater by a factor of approximately 10. For both methods of data collection, the results of the spectroscopic analysis showed an early increase in deoxygenated hemoglobin (Hbr) with no evidence for a corresponding decrease in oxygenated hemoglobin (HbO(2)). Evidence for increased oxygen consumption (CMRO(2)) was obtained by converting the fractional changes in blood volume (Hbt) into estimates of changes in blood flow (Grubb et al., 1974) and using the resulting time course to scale the fractional changes in Hbr. The results show an early increase CMRO(2) peaking approximately 2 s after stimulation onset. Using these methods, we find evidence for increased oxygen consumption following increased neural activity even at low levels of stimulation intensity.

Algorithms↗
PubMed2000

The effect of pelvic ileal reservoir volume and antiperistaltic reflux on emptying efficiency.

PURPOSE: The emptying efficiency of four different designs of pelvic ileal reservoir was compared using two different techniques of measurement. METHOD: Thirty-four patients were studied one year after restorative proctocolectomy. In each the ileal reservoir was filled with methyl cellulose paste labeled with 51chromium-chromate and technetium Tc 99m-diethylenetriamine pentaacetic acid. Percentage evacuation was calculated from 1) the difference in 51chromium activity between the recovered effluent and the total paste administered and 2) gamma camera measurements of technetium Tc 99m-diethylenetriamine pentaacetic acid activity within the ileal reservoir before and after evacuation. RESULTS: Median evacuation using the 51chromium method was 84, 90, 70, and 75 percent for the W40, W30, J40, and J30 reservoirs respectively. The results were not significantly different from those obtained using the gamma camera: 83, 87, 67, and 71 percent (P = not significant). Patients with either type of W reservoir evacuate isotope-labeled paste more efficiently than patients with J40 reservoirs (P < 0.05 and P < 0.001, respectively) but not J30 reservoirs (P = not significant). However, if the actual volume of paste evacuated during a visit to the lavatory is measured, it is greatest for J40 reservoirs (median, 300 ml compared with 258 ml for W40, 289 ml for W30, and 268 ml for J30; P = not significant). CONCLUSIONS: Gamma camera measurement of ileal reservoir emptying is as accurate as our previous standard technique and provides a qualitative record of pouch evacuation, which may reveal reasons for inefficient emptying. The gamma camera images reveal that the difference in emptying percentage between W and J pouches is because of reflux of paste into the afferent ileum occurring more frequently in J pouches than in W pouches. The effect of this phenomenon on emptying is more than compensated for by the increase in reservoir capacity created by the reflux.

Adolescent↗
PubMed2000

The prevalence of polycystic ovaries in women with a history of gestational diabetes.

OBJECTIVE: Women with a history of gestational diabetes mellitus (GDM) and women with polycystic ovary syndrome (PCOS) both demonstrate abnormalities in insulin action and secretion, and both are at increased risk of developing type 2 diabetes. To determine whether these similarities reflect a common pathophysiological basis, we examined the prevalence of ultrasound-based polycystic ovarian morphology in a large multiethnic group of women with a history of GDM and a group of women who had normal glucose tolerance during pregnancy. PATIENTS AND DESIGN: We studied 91 women with previous GDM (48 European, 20 South Asian, 10 Afro-Caribbean and 13 of other or mixed ethnicity) and 73 normoglycaemic control women (56 European, one South Asian, 14 Afro-Caribbean and two of other or mixed ethnicity), a median (interquartile range) of 20 (11-36) and 29 (17-49) months postpartum, respectively. A detailed history was taken, and the prevalence of PCO morphology on ultrasound scan was assessed. Fasting lipids, insulin, glucose status, gonadotrophins and testosterone were measured. Estimates of beta-cell function (%B) and insulin sensitivity (%S) were derived using the HOMA algorithm. RESULTS: Women with previous GDM had higher fasting glucose (5.4 (4. 8-6.0) vs. 4.7 (4.4-5.0) mmol/l, P<0.0001) and features reminiscent of syndrome X: higher BMI (26.4 (22.8-31.4) vs. 23.8 (21. 0-27.5) kg/m2, P = 0.002), waist/hip ratio (0.82 (0.79-0.88) vs. 0. 77 (0.73-0.81), P<0.0001), fasting insulin (165 (68-299) vs. 54 (24-156) pmol/l, P<0.0001), triglycerides (1.1 (0.8-1.6) vs. 0.8 (0.6-1.1) mmol/l, P<0.0001) and lower insulin sensitivity (%S) (27 (16-62) vs. 86 (34-139)%, P<0.0001) compared to control women. The prevalence of PCO was higher in the previous GDM group than in the control subjects (47/91 (52%) vs. 20/73 (27%), chi2 = 9.86, P = 0. 002 overall, odds ratio 2.7, P = 0.007 by logistic regression allowing for ethnicity). There was no difference in any metabolic parameter between the post-GDM PCO group and the post-GDM normal ovaries group, but irregular cycles were more prevalent in the PCO group (22/47 (47%) vs. 9/44 (21%), chi2 = 7.03, P = 0.008). CONCLUSIONS: We found a higher prevalence of polycystic ovarian morphology in women with a history of gestational diabetes. Among the women with previous gestational diabetes, irregular cycles were more prevalent in the PCO group than in the women with normal ovarian morphology, but no other differences in endocrine or metabolic parameters were detected. These findings confirm an association between PCO and gestational diabetes and suggest that women with gestational diabetes display metabolic abnormalities irrespective of ovarian morphology.

Blood Glucose↗
PubMed2000

Patient satisfaction with a new nurse practitioner service.

In the UK the role of the Nurse Practitioner (NP) has been slower to develop than in the USA (Tye 1997). However, since its inception, studies of the role have found positive results in areas of patient satisfaction (Touche Ross 1994). James and Pyrgos (1989) reported 94% of patients suitable to seen by a NP would use a NP if introduced. A study by Freij et al. (1996) concluded that emergency NPs were as competent at interpreting X-rays as casualty officers. Despite such evidence, Meek et al. (1995) noted opposition to this new advanced practice from other disciplines who wished to maintain the 'status quo'. In light of these findings, a study was undertaken to examine the new NP Service at Antrim Hospital, Northern Ireland. A patient satisfaction survey, a retrospective X-ray audit and a subjective assessment by other disciplines, were carried out in order to evaluate the service.

Clinical Competence↗
PubMed2000

Cooling-rate effects in a model of glasses

Using Monte Carlo simulations we study cooling-rate effects in a three-dimensional Ising model with four-spin interactions. During coarsening, this model develops growing energy barriers, which at low temperature lead to very slow dynamics. We show that the characteristic zero-temperature length increases very slowly with the inverse cooling rate, similarly to the behavior of ordinary glasses. For computationally accessible cooling rates the model undergoes an ideal glassy transition, i.e., the glassy transition for a very small cooling rate coincides with a thermodynamic singularity. We also study the cooling of this model with a certain fraction of spins fixed. Due to such heterogeneous crystallization seeds, the final state strongly depends on the cooling rate. Only for a sufficiently fast cooling rate does the system end up in a glassy state, while slow cooling inevitably leads to a crystal phase.

Journal Article↗
PubMed2000

Slow dynamics of ising models with energy barriers

Using Monte Carlo simulations we study the dynamics of three-dimensional Ising models with nearest-, next-nearest-, and four-spin (plaquette) interactions. During coarsening, such models develop growing energy barriers, which leads to very slow dynamics at low temperature. As already reported, the model with only the plaquette interaction exhibits some of the features characteristic of ordinary glasses: strong metastability of the supercooled liquid, a weak increase of the characteristic length under cooling, stretched-exponential relaxation, and aging. The addition of two-spin interactions, in general, destroys such behavior: the liquid phase loses metastability and the slow-dynamics regime terminates well below the melting transition, which is presumably related with a certain corner-rounding transition. However, for a particular choice of interaction constants, when the ground state is strongly degenerate, our simulations suggest that the slow-dynamics regime extends up to the melting transition. The analysis of these models leads us to the conjecture that in the four-spin Ising model domain walls lose their tension at the glassy transition and that they are basically tensionless in the glassy phase.

Journal Article↗
PubMed2000

Comparison of 21 vs. 25 mm gastrojejunostomy in the gastric bypass procedure--early results.

BACKGROUND: Many bariatric surgeons consider a small gastrojejunostomy stoma critical to the success of gastric bypass. METHODS: We retrospectively compared a 21 vs. 25 mm gastrojejunostomy in 50 patients undergoing gastric bypass for morbid obesity. RESULTS: 31 patients were constructed with a 21 mm EEA, group I, and 19 with a 25 mm, group II. Average percent of excess body weight lost was 61%, 65%, and 64% at 12, 15, and 18 months follow-up in the group I patients, vs. 61%, 67%, and 69% in the group B patients. Differences were not significant. Complaints of nausea, vomiting, and/or dysphagia were similar between the groups. CONCLUSION: The choice of a 21 or 25 mm gastrojejunostomy does not appear to alter the success of gastric bypass surgery and can be based upon surgeon preference.

Body Mass Index↗
PubMed2000

A comparative analysis of sextant and an extended 11-core multisite directed biopsy strategy.

PURPOSE: The 3 tumor locations unsampled by conventional sextant biopsies that have been identified on composite 3-dimensional reconstruction of 180 radical prostatectomy specimens are the anterior transition zone, midline peripheral zone and inferior portions of the anterior horn in the peripheral zone. We evaluated an 11-core multisite directed biopsy scheme incorporating these alternate areas and conventional sextant biopsies in 362 patients from 2 institutions. MATERIALS AND METHODS: Patients without a prior diagnosis of cancer underwent ultrasound guided 11-core biopsies which included conventional sextant and 3 alternate sites. All specimens were separated for specific location identification. Biopsy was performed in 183 patients at MD Anderson Cancer Center (group 1) and in 179 at Toronto General Hospital (group 2). All group 2 and 54% of group 1 patients (98 of 183) had a prior biopsy negative for cancer. RESULTS: Median prostate specific antigen was higher in group 2 than in group 1 patients (11.5 versus 9.5 ng./ml., p = 0.016). Overall a 33% increase (36 of 110 patients) in cancer detection was observed when biopsy technique included the alternate areas (p = 0.0021). The anterior horn was the most frequently positive biopsy site followed by the transition zone and midline sites. The 11-core technique had significantly better cancer detection rates when digital rectal examination and transrectal ultrasound were normal, and in men with serum prostate specific antigen between 4.1 and 10 ng./ml. CONCLUSIONS: Biopsies of the alternate sites suggested by our simulation studies are feasible and reproducible. This new strategy significantly enhanced (p = 0.0075) prostate cancer detection compared to conventional sextant biopsies in men undergoing a repeat procedure.

Adult↗
PubMed2000

Relative expression of type IV collagenase, E-cadherin, and vascular endothelial growth factor/vascular permeability factor in prostatectomy specimens distinguishes organ-confined from pathologically advanced prostate cancers.

The tumor grade (Gleason score) in the biopsy and pretherapy prostate-specific antigen level do not accurately predict disease outcome of individual patients' prostate cancer. We used a rapid colorimetric in situ hybridization technique to evaluate the expression level of E-cadherin (which affects cell cohesion); matrix metalloproteinases (MMPs) types 2 and 9 (which affect invasion); and vascular endothelial growth factor/vascular permeability factor (which affects angiogenesis) in archival prostatectomy specimens from 40 patients. Intratumoral heterogeneity for gene expression (edge versus center versus perineural area) was more pronounced in advanced cancers than in those that were organ confined. Regardless of Gleason score, the highest expression level for E-cadherin was found in the center or perineural area of the tumors, whereas the highest expression levels for MMP-2 and MMP-9 were associated with the invasive edge. The relationship between advancing pathological stage and expression of all four metastasis-related genes was highly significant. Decreased expression of E-cadherin and increased expression of MMP-2, MMP-9, and vascular endothelial growth factor/vascular permeability factor were associated with the Gleason score of the tumors. Irrespective of serum prostate-specific antigen level or Gleason score, the ratio between expression of MMPs and E-cadherin at the invasive edge of tumors exhibited the strongest association with nonorgan-confined prostate cancer. These data suggest that the relative expression of metastasis-related genes in radical prostatectomy specimens can distinguish between organ-confined and advanced prostate cancers and provides the rationale for a prospective study correlating gene expression in pretherapy core biopsies with outcome.

Biopsy↗
PubMed2000

Barrett's oesophagus: results from a 13-year surveillance programme.

OBJECTIVES: To review the results of a 13-year surveillance programme of patients with Barrett's oesophagus to determine the incidence of adenocarcinoma. Although the risk of cancer in Barrett's oesophagus is well established, the magnitude of this risk is still controversial. DESIGN: Records of all patients with histologically confirmed Barrett's oesophagus in our 13-year surveillance programme were examined retrospectively. SETTING: Integrated gastroenterology and gastrointestinal surgical service in a large teaching hospital. PARTICIPANTS: During the study period, 597 patients had a diagnosis of Barrett's oesophagus; of these, 357 entered a yearly endoscopy and biopsy surveillance programme. MAIN OUTCOME MEASURES: The development of oesophageal adenocarcinoma. RESULTS: After a mean follow-up of 43 months, 12 patients, all with specialized epithelium, developed adenocarcinoma (11 men), an incidence for men of one cancer per 69 patient-years; and for women, one cancer per 537 patient-years follow-up (P < 0.01). If only patients with specialized mucosa were included the incidence of cancer was one per 95 patient-years of follow-up (men, one per 61 patient-years; women, one per 468 patient-years). CONCLUSIONS: Whilst the role of screening patients with Barrett's oesophagus remains controversial, this study supports the routine surveillance of male patients with specialized epithelium.

Adenocarcinoma↗
PubMed1999

Calcium-activated potassium conductances contribute to action potential repolarization at the soma but not the dendrites of hippocampal CA1 pyramidal neurons.

Evidence is accumulating that voltage-gated channels are distributed nonuniformly throughout neurons and that this nonuniformity underlies regional differences in excitability within the single neuron. Previous reports have shown that Ca2+, Na+, A-type K+, and hyperpolarization-activated, mixed cation conductances have varying distributions in hippocampal CA1 pyramidal neurons, with significantly different densities in the apical dendrites compared with the soma. Another important channel mediates the large-conductance Ca2+-activated K+ current (IC), which is responsible in part for repolarization of the action potential (AP) and generation of the afterhyperpolarization that follows the AP recorded at the soma. We have investigated whether this current is activated by APs retrogradely propagating in the dendrites of hippocampal pyramidal neurons using whole-cell dendritic patch-clamp recording techniques. We found no IC activation by back-propagating APs in distal dendritic recordings. Dendritic APs activated IC only in the proximal dendrites, and this activation decayed within the first 100-150 micrometer of distance from the soma. The decay of IC in the proximal dendrites occurred despite AP amplitude, plus presumably AP-induced Ca2+ influx, that was comparable with that at the soma. Thus we conclude that IC activation by action potentials is nonuniform in the hippocampal pyramidal neuron, which may represent a further example of regional differences in neuronal excitability that are determined by the nonuniform distribution of voltage-gated channels in dendrites.

Action Potentials↗