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J Marshall

Publications and source records attributed to J Marshall.

At least 91 records · Page 5Linked to original sources
PubMed2000

Inhibition of IL-12 production in human monocyte-derived macrophages by TNF.

IL-12 is a pivotal cytokine that links the innate and adaptive immune responses. TNF-alpha also plays a key role in orchestrating inflammation and immunity. The reciprocal influence of these two inflammatory mediators on each other may have significant impact on the cytokine balance that shapes the type and extent of immune responses. To investigate the relationship between TNF-alpha and IL-12 production, we analyzed the effects of exposure of human monocyte-derived macrophages to TNF-alpha on LPS- or Staphylococcus aureus-induced IL-12 production in the presence or absence of IFN-gamma. TNF-alpha is a potent inhibitor of IL-12 p40 and p70 secretion from human macrophages induced by LPS or S. aureus. IL-10 is not responsible for the TNF-alpha-mediated inhibition of IL-12. TNF-alpha selectively inhibits IL-12 p40 steady-state mRNA, but not those of IL-12 p35, IL-1alpha, IL-1beta, or IL-6. Nuclear run-on analysis identified this specific inhibitory effect at the transcriptional level for IL-12 p40 without down-regulation of the IL-12 p35 gene. The major transcriptional factors identified to be involved in the regulation of IL-12 p40 gene expression by LPS and IFN-gamma, i.e., c-Rel, NF-kappaB p50 and p65, IFN regulatory factor-1, and ets-2, were not affected by TNF-alpha when examined by nuclear translocation and DNA binding. These data demonstrate a selective negative regulation on IL-12 by TNF-alpha, identifying a direct negative feedback mechanism for inflammation-induced suppression of IL-12 gene expression.

Biological Transport↗
PubMed2000

Involvement of cytosolic phospholipase A2 and secretory phospholipase A2 in arachidonic acid release from human neutrophils.

The purpose of this study was to define the role of secretory phospholipase A2 (sPLA2), calcium-independent PLA2, and cytosolic PLA2 (cPLA2) in arachidonic acid (AA) release from fMLP-stimulated human neutrophils. While fMLP induced the release of extracellular sPLA2 activity and AA, 70% of sPLA2 activity remained associated with the cell. Treatment with the cell-impermeable sPLA2 inhibitors DTT or LY311-727, or the anti-sPLA2 Ab 3F10 all inactivated extracellular sPLA2 activity, but had minimal effect on neutrophil AA mass release. In contrast, coincubation of streptolysin-O toxin-permeabilized neutrophils with DTT, LY311-727, or 3F10 all decreased [3H8]AA release from [3H8]AA-labeled, fMLP-stimulated cells. Exposure to fMLP resulted in a decrease in the electrophoretic mobility of cPLA2, a finding consistent with cPLA2 phosphorylation, and stimulated the translocation of cPLA2 from cytosolic to microsomal and nuclear compartments. The role of cPLA2 was further evaluated with the cPLA2 inhibitor methyl arachidonyl fluorophosphonate, which attenuated cPLA2 activity in vitro and decreased fMLP-stimulated AA mass release by intact neutrophils, but had no effect on neutrophil sPLA2 activity. Inhibition of calcium-independent PLA2 with haloenol lactone suicide substrate had no effect on neutrophil cPLA2 activity or AA mass release. These results indicate a role for cPLA2 and an intracellular or cell-associated sPLA2 in the release of AA from fMLP-stimulated human neutrophils.

Arachidonic Acid↗
PubMed2000

Papillofoveal traction in macular hole formation: the role of optical coherence tomography.

OBJECTIVES: To determine the validity of the assumption that optical coherence tomographic scans of macular holes have a discrete linear signal (DLS) that represents a detached posterior vitreous face, and to analyze the DLS in macular hole pathogenesis. METHODS: Optical coherence tomographic scans were taken of 3 situations in which the vitreous conditions were known: (1) dissected intact vitreous, (2) clinically evident Weiss rings, and (3) maculae before and after saccades in eyes without a biomicroscopic posterior vitreous detachment. In addition, 70 eyes of 35 patients with macular holes underwent clinical examination and optical coherence tomographic scanning that passed through the optic disc and the fovea or macular hole. RESULTS: Spatial properties of the DLS matched those of the posterior vitreous face in the situations examined. Of the 70 eyes, 16 (23%) had a biomicroscopic posterior vitreous detachment, whereas a DLS was demonstrated in 40 (57%). Of the 54 eyes without a biomicroscopic posterior vitreous detachment, 18 (33%) had a DLS attached focally to the optic disc margin and the fovea or macular hole. All 7 of the "can opener" holes examined had a nasally "hinged" central flap, 6 with a focally attached DLS. CONCLUSIONS: The DLS corresponds to the posterior vitreous face. Anteronasal papillofoveal traction may generate some macular holes.

Fovea Centralis↗
PubMed2000

Optical coherence tomography of melanocytoma.

PURPOSE: To evaluate the use of optical coherence tomography in differentiating between melanocytoma and choroidal melanoma. METHODS: Case reports. Three consecutive patients with melanocytoma were scanned using optical coherence tomography. RESULTS: Optical coherence tomography showed lesions with a high reflectance signal anteriorly and optical shadowing behind, corresponding to the melanocytomas. The high signal was continuous with the retinal nerve fiber layer, consistent with known growth patterns of melanocytoma. CONCLUSION: Optical coherence tomography may be useful in differentiating melanocytoma from choroidal melanocytic lesions.

Adult↗
PubMed2000

Comparison between optical coherence tomography and fundus fluorescein angiography for the detection of cystoid macular edema in patients with uveitis.

PURPOSE: To compare optical coherence tomography (OCT) with fundus fluorescein angiography (FFA) for the detection of cystoid macular edema (CME) in patients with uveitis. DESIGN: Prospective comparative observational series. PARTICIPANTS: One hundred twenty-one eyes of 58 patients with uveitis of varied causes (seven patients were studied twice). TESTING: Patients with suspected CME underwent OCT scanning followed by FFA at the same visit. MAIN OUTCOME MEASURES: Detection and distribution of macular edema. RESULTS: One hundred eight eyes had similar results on both OCT and FFA in that 67 eyes had CME and 41 eyes had no CME. In 10 eyes subretinal fluid was detected on OCT but not FFA. Five of these eyes had CME on FFA but not OCT. Three other eyes had CME that was detected by FFA but not by OCT. Compared with FFA, the OCT sensitivity for detecting CME was 96% (including the eyes with subretinal fluid), and the OCT specificity was 100%. CONCLUSIONS: OCT is as effective at detecting CME as is FFA but is superior in demonstrating axial distribution of fluid.

Exudates and Transudates↗
PubMed2000

Effects of BG9719 (CVT-124), an A1-adenosine receptor antagonist, and furosemide on glomerular filtration rate and natriuresis in patients with congestive heart failure.

OBJECTIVES: To determine the effects of furosemide and the selective A1 adenosine receptor BG9719 on renal function in patients with congestive heart failure (CHF). BACKGROUND: Studies suggest that adenosine may affect renal function by various mechanisms, but the effects of blockade of this system in humans is unknown. In addition, the effects of a therapeutic dose of furosemide on glomerular filtration rate (GFR) and renal plasma flow (RPF) in heart failure patients are controversial. METHODS: On different days, 12 patients received placebo, BG9719 and furosemide. Glomerular filtration rate, RPF and sodium and water excretion were assessed immediately following drug administration. RESULTS: Glomerular filtration rate was 84 +/- 23 ml/min/1.73m2 after receiving placebo, 82 +/- 24 following BG9719 administration and a decreased (p < 0.005) 63 +/- 18 following furosemide. Renal plasma flow was unchanged at 293 +/- 124 ml/min/1.73m2 on placebo, 334 +/- 155 after receiving BG9719 and 374 +/- 231 after receiving furosemide. Sodium excretion increased from 8 +/- 8 mEq following placebo administration to 37 +/- 26 mEq following BG9719 administration. In the six patients in whom it was measured, sodium excretion was 104 +/- 78 mEq following furosemide administration. CONCLUSIONS: Natriuresis is effectively induced by both furosemide and the adenosine A1 antagonist BG9719 in patients with CHF. Doses of the two drugs used in this study did not cause equivalent sodium and water excretion but only furosemide decreased GFR. These data suggest that adenosine is an important determinant of renal function in patients with heart failure.

Adult↗
PubMed2000

Hyperopic photorefractive keratectomy with the erodible mask and axicon system: two year follow-up.

PURPOSE: To evaluate efficacy and long-term stability of hyperopic photorefractive keratectomy (H-PRK) using the erodible mask and Axicon system. SETTING: Department of Ophthalmology, St. Thomas' Hospital, London, England. METHODS: Forty-three patients (43 eyes), with a mean preoperative refraction (spherical equivalent) of +4.54 diopters (D) (range +1.75 to +7.50 D), were treated using an Apex Plus(R) excimer laser (Summit Technology). This uses an erodible mask to ablate a 6. 50 mm diameter hyperopic correction and an Axicon to fashion a 1.50 mm blend zone around the correction. The overall ablation diameter was 9.50 mm. Follow-up was 2 years. RESULTS: At 2 years, the mean manifest refraction was +0.16 D (range +4.125 to -4.000 D), with the induced correction appearing stable after 9 months. Based on the Munnerlyn algorithm, predictability was acceptable for corrections up to +4.50 D, with 68% of eyes within +/-1.00 D of the predicted correction. It was poorer for +6.00 D corrections, with 33% of eyes within +/-1.00 D of that expected. Patient satisfaction was high. Forty eyes (93%) had an improvement in uncorrected near visual acuity and 37 (86%), an improvement in uncorrected distance acuity. A peripheral ring of haze, 6.5 mm in diameter, appeared in all eyes 1 month postoperatively. Its intensity was maximal at 3 to 9 months and then diminished over time. There were no significant differences in measurements of the central corneal transparency at 12 and 24 months and those preoperatively. Measurements of flicker contrast sensitivity, forward light scatter (glare), and scotopic halos showed no significant differences between preoperative values and those measured after 6 months. CONCLUSIONS: Achieved H-PRK corrections with the erodible mask and Axicon system agreed closely with the Munnerlyn algorithm, with refractive stability after 9 months. Predictability was acceptable for corrections up to +4.50 D. Axial corneal transparency was not compromised and visual performance, in terms of best spectacle-corrected visual acuity, forward light scatter, and night halos, was not impaired.

Adult↗
PubMed2000

Potentiation of neuronal L calcium channels by IGF-1 requires phosphorylation of the alpha1 subunit on a specific tyrosine residue.

Insulin-like growth factor 1 (IGF-1) rapidly potentiates N and L calcium channel currents in cerebellar granule neurons by an unknown mechanism. Here, we show that the L channel alpha1C subunit is tyrosine phosphorylated in response to IGF-1. Moreover, expression of kinase-dead c-Src in neurons or acute block of Src family kinases with a cell-permeable inhibitor specifically blocks L channel potentiation. Purified Src kinase phosphorylates tyrosine residue Y2122 of the C terminus of neuronal alpha1C in vitro, and c- and v-Src directly bind the C terminus. When expressed in neuroblastoma cells, point mutation of Y2122 prevents both tyrosine phosphorylation of alpha1C and IGF-1 potentiation. Our data provide a biochemical mechanism whereby phosphorylation of a single specific tyrosine residue rapidly modifies ion channel physiology.

Animals↗
PubMed2000

Service use and costs of people with dual diagnosis in South London.

OBJECTIVE: To compare the service use and costs of individuals who have a dual diagnosis of psychosis and substance abuse with those who have a diagnosis of psychosis but no substance abuse. METHOD: Patients with psychosis were identified and a representative sample were interviewed. Six-month service use was measured and costs calculated. Regression models were developed to predict costs from background characteristics and dual diagnosis status. RESULTS: A greater proportion of the patients with dual diagnosis used community psychiatric nurses, in-patient care and the emergency clinic. The regression analysis revealed that dual diagnosis patients had significantly higher 'core' psychiatric service costs (a difference of pound sterling 1362) and non-accommodation service costs (pound sterling 1360) than non-dual-diagnosis patients. The difference when all services were analysed was pound sterling 1046, but this was not statistically significant. CONCLUSION: Specific interventions for dual diagnosis patients should be introduced and assessed in terms of individual outcomes, service use and costs.

Adult↗
PubMed2000

Detection of retinal lesions after telemedicine transmission of digital images.

PURPOSE/BACKGROUND: To assess whether loss of image resolution or colour and subsequent telemedicine transmission of digital images affects the accuracy of retinal lesion detection by ophthalmologists when compared with the original transparencies. METHODS: Fifteen ophthalmologists of different experience independently scored 11 retinal images for pathological signs. The images were presented as either transparencies or colour and monochrome digital images, which had been transmitted via telephone lines to a geographically remote location. One patient's eye was also imaged using scanning laser ophthalmosocopy (SLO) which produced a dynamic black and white digital image. ANOVA analysis was performed. RESULTS: Total scores were higher for transparencies than colour (p = 0.0003) or black and white digital images (p = 0.00006). Expert observers (n = 5) considered separately showed no significant difference of accuracy between transparencies and either colour digital (p = 0.09) or monochrome digital images (p = 0.11). Experts were better than trainees at detecting pathology from less familiar images: total score (p = 0.02), colour digital (p = 0.03), monochrome digital (p = 0.02) and SLO images (p = 0.004). CONCLUSION: Experienced observers can identify sight-threatening retinal pathology from poorer-resolution digital images that have been transmitted by telemedicine. They can also adapt to viewing less familiar images such as black and white digital or SLO images.

Analysis of Variance↗
PubMed2000

Characterization of the oligosaccharide structures associated with the cystic fibrosis transmembrane conductance regulator.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a plasma membrane-associated glycoprotein. The protein can exist in three different molecular weight forms of approximately 127, 131, and 160 kDa, representing either nonglycosylated, core glycosylated, or fully mature, complex glycosylated CFTR, respectively. The most common mutation in cystic fibrosis (CF) results in the synthesis of a variant (DeltaF508-CFTR) that is incompletely glycosylated and defective in its trafficking to the cell surface. In this study, we have analyzed the oligosaccharide structures associated with the different forms of recombinant CFTR, by expressing and purifying the channel protein from either mammalian Chinese hamster ovary (CHO) or insect Sf9 cells. Using glycosidases and FACE analysis (fluorophore-assisted carbohydrate electrophoresis) we determined that purified CHO-CFTR contained polylactosaminoglycan (PL) sequences, while Sf9-CFTR had only oligomannosidic saccharides with fucosylation on the innermost GlcNAc. The presence of PL sequences on the recombinant CHO-CFTR is consistent with a normal feature of mammalian processing, since endogenous CFTR isolated from T84 cells displayed a similar pattern of glycosylation. The present study also reports on the use of FACE for the qualitative analysis of small amounts of glycoprotein oligosaccharides released enzymatically.

Amidohydrolases↗
PubMed2000

Use of a screen log to audit patient recruitment into multiple randomized trials in the intensive care unit. Canadian Critical Care Trials Group.

OBJECTIVE: To develop and evaluate a screen log for monitoring enrollment in multiple randomized clinical trials conducted in a single center. SETTING: University-affiliated 20-bed tertiary care medical-surgical intensive care unit (ICU). PATIENTS: Consecutive ICU patients admitted between April 1995 and March 1997. METHODS: We developed a screen log for multicentered studies conducted in our ICU. Using a multiple-project, unicenter perspective, we evaluated the screen log as a tool for monitoring eligibility and enrollment of patients in four multicentered randomized trials focused on stress ulcer prophylaxis, blood transfusion thresholds, immunotherapy for sepsis and mechanical ventilation strategies. RESULTS: The screen log was used as an instrument to monitor trial execution. We recorded all aspects of study enrollment and created a taxonomy of reasons for nonenrollment into each trial. We calculated enrollment efficiency rates and used these data to develop strategies to maximize accrual. The screen log became a communication tool that fostered research-oriented continuous quality improvement initiatives for the management of concurrently conducted randomized trials in our ICU. CONCLUSIONS: Intensivists participating in several clinical trials may be interested in monitoring and maximizing enrollment when conducting multiple studies and understanding the influence of each trial on enrollment into the others. The unicenter, multiple-project screen log is one tool that may help to achieve these goals.

Canada↗
PubMed2000

Crystallization and preliminary X-ray analysis of the auxin receptor ABP1.

Auxin-binding protein (ABP1) is an important receptor for the plant hormone auxin that is involved with many growth and developmental responses in plants. The maize ABP1 gene has been expressed in insect cells, purified and crystallized. Type II crystals are monoclinic, with two glycosylated homodimers in the asymmetric unit, and diffract to 1.9 A using synchrotron radiation.

Crystallization↗
PubMed2000

Mechanism related to reduction of intraocular pressure by melanocortins in rabbits.

AIM: To investigate whether the ocular hypotensive effect of alpha melanocyte stimulating hormone (MSH) is related to eicosanoids or cyclic AMP (cAMP). METHODS: Intraocular pressure (IOP) readings were taken at a similar time on the day before and after a single dose of topical MSH. Changes in the levels of prostaglandin E(2) (PGE(2)) and prostacyclin in incubated iris ciliary body (ICB) explants were measured by specific radioimmunoassay (RIA). Incubated ICB explants were exposed to MSH or adrenaline (epinephrine) for a week. In addition, cAMP levels in the medium were determined following short term incubation using RIA. RESULTS: A significant dose related reduction in IOP was noted with topical MSH (mean (SD) maximal effect 4.5 (0.1) mm Hg (21%); p<0.001 v appropriate baseline) which persisted up to 6 hours (p=0.05). MSH treated ICB explants showed a 1.5-fold increase in PGE(2) and prostacyclin levels (p<0.001 for each parameter) while cAMP levels were increased twofold (p<0.001). CONCLUSIONS: A single application of MSH caused a sustained dose related ocular hypotensive effect with no side effects. An increase in eicosanoid and cAMP levels following ICB exposure to MSH indicated their involvement in MSH induced ocular hypotension. MSH and its analogues might have clinical relevance as antiglaucoma drugs with fewer side effects because of their antiallergic and anti-inflammatory properties.

6-Ketoprostaglandin F1 alpha↗
PubMed2000

Firearm safety counseling in primary care pediatrics: a randomized, controlled trial.

CONTEXT: Physicians have been encouraged to counsel families about risks associated with gun ownership, but the effectiveness of physician counseling regarding gun safety is unknown. OBJECTIVE: To determine the effectiveness of gun safety counseling during well-child care visits. DESIGN: Group randomized, controlled trial. Physicians, nurse practitioners, and physician assistants were randomized to either the intervention group or a control group. SETTING: Group Health Cooperative, a staff-model health maintenance organization. Patients. Consecutive sample of families (n = 1295) seen for a scheduled appointment for well-child care for a child <18 years of age. Of the families originally scheduled for a visit, 80. 3% were seen and completed the outcomes surveys. INTERVENTION: Each family in the intervention group was given a 60-second message by their practitioner that depended on the presence of guns in the home. Families without guns were informed of the health risks associated with gun ownership and given a standard information pamphlet. Families with guns were given the same information about risks and were told that if they chose to keep a gun, they should store it locked and unloaded. They were given instructions on storage and a folder with material, including the same pamphlet, a letter from the police department, written storage guidelines, and discount coupons for gun storage devices. MAIN OUTCOME MEASURE: Changes in the following self-reported events: 1) acquisition of a safe storage device; 2) removal of firearms from the home; and 3) acquisition of firearms. Results. There were no important differences between intervention and control groups in the rate of acquisition of new guns (intervention: 1.3% vs control:.9%) after the intervention. Among households with guns at baseline, there were also no differences between groups in the removal of guns (intervention: 6.7% vs control: 5.7%), but there was a fairly large nonsignificant difference in the proportion who purchased trigger locks (intervention: 8.0% vs control: 2.5%). CONCLUSIONS: A single firearm safety-counseling session during well-child care, combined with economic incentives to purchase safe storage devices, did not lead to changes in household gun ownership and did not lead to statistically significant overall changes in storage patterns.

Adolescent↗
PubMed2000

Cationic lipid structure and formulation considerations for optimal gene transfection of the lung.

Enhanced gene transduction to the lung using cationic lipids could be attained through optimization of the structure of the lipids and the formulation of the cationic lipid:plasmid DNA (pDNA) complexes. We have expanded on our earlier observation of the importance of the structural orientation of the cationic lipid headgroup. Through the synthesis of a number of matched pairs of cationic lipids differing only in the configuration of their headgroup, we confirmed that those harboring a T-shape headgroup are more active than their linear counterparts, at least when tested in the lungs of BALB/c mice. Additionally, we demonstrated that not only are the structural considerations of these cationic lipids important, but also their protonation state, the free base being invariably more active than its salt counterpart. The salt forms of cationic lipids bound pDNA with greater avidity, which may have affected their subsequent intracellular dissolution and transit of the pDNA to the nucleus. Inclusion of a number of frequently used solutes in the vehicle severely inhibited the gene transfection activity of the cationic lipids. The selection of neutral co-lipids was also an important factor for overall transfection activity of the formulation, with significant gains in transfection activity realized when diphytanoylphosphatidylethanolamine or dilinoleoylphosphatidylethanolamine were used in lieu of dioleoylphosphatidylethanolamine. Finally, we showed that a transacylation reaction could occur between the cationic lipid and neutral co-lipid which reduced the transfection activity of the complexes. It is the hope that as our understanding of the many factors that influence the activity of these cationic lipid:pDNA complexes improves, formulations with much greater potency can be realized for use in the treatment of pulmonary diseases.

Animals↗