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N Jones

Publications and source records attributed to N Jones.

At least 55 records · Page 3Linked to original sources
PubMed2001

Multiple ErbB-2/Neu Phosphorylation Sites Mediate Transformation through Distinct Effector Proteins.

Amplification of the type I receptor tyrosine kinase ErbB-2 (HER2/Neu) is observed in 20-30% of human mammary carcinomas, correlating with a poor clinical prognosis. We have previously demonstrated that four (Tyr(1144), Tyr(1201), Tyr(1226/1227), or Tyr(1253)) of the five known Neu/ErbB-2 autophosphorylation sites can independently mediate transforming signals. The transforming potential of at least two of these autophosphorylation sites (Tyr(1144) and Tyr(1226/1227)) has been further correlated with their ability to associate with Grb2 and Shc adapter proteins, respectively. To confirm the specificity of these interactions, we have created a series of second site mutants in these phosphorylation sites. The results showed that Grb2 recruitment to site 1144 is absolutely required for transforming signal from this autophosphorylation site, whereas association of Shc-mediated transformation is dependent on conservation of the NPXY motif spanning Tyr(1227). A stretch of amino acid identity around tyrosines 1201 (ENPEYLTP)and 1253 (ENPEYLDL) exists, and mutation of key residues within this motif reveals distinct requirements for an intact protein tyrosine-binding protein (NPXY). We show that DOK-R, a protein tyrosine-binding site-containing protein implicated in Ras signaling, interacts with Neu/ErbB-2 at Tyr(1253) as do two unidentified proteins, p150 and p34, the latter correlating with transformation. Together these data argue that ErbB-2/Neu is capable of mediating transformation through distinct effector pathways.

Amino Acid Motifs↗
PubMed2001

Rickettsia africae, a tick-borne pathogen in travelers to sub-Saharan Africa.

BACKGROUND: African tick-bite fever occurs after contact with ticks that carry Rickettsia africae and that parasitize cattle and game. Sporadic reports suggest that this infection has specific clinical and epidemiologic features. METHODS: We studied patients who were tested for a rickettsial disease after returning from a visit to Africa or Guadeloupe. To assess the value of the microimmunofluorescence assay, Western blotting, and cross-adsorption assays, we compared the results of these tests in 39 patients in whom African tick-bite fever had been confirmed by the polymerase-chain reaction assay, cell culture, or both; 50 patients with documented R. conorii infection; and 50 blood donors. These diagnostic criteria were then applied to 376 additional patients who had returned from southern Africa and 2 who had returned from Guadeloupe and whose serum was being tested for rickettsial disease. RESULTS: In the 39 patients with direct evidence of R. africae infection, the combination of microimmunofluorescence assay, Western blotting, and cross-adsorption assays showing antibodies specific for R. africae had a sensitivity of 0.56; however, each test had a positive predictive value and a specificity of 1.0. An additional 80 patients were found to have an R. africae infection on the basis of these serologic criteria. Infections with R. africae were acquired by visitors to 11 African countries and Guadeloupe. The illness was generally mild and was characterized by a rash in 46 percent of the patients; the rash was usually maculopapular or vesicular and rarely purpuric. Ninety-five percent of patients had an inoculation eschar or eschars, and 54 percent of these patients had multiple eschars, a finding that is unusual in patients with rickettsial infection. CONCLUSIONS: In this series, R. africae was the cause of nearly all cases of tick-bite rickettsiosis in patients who became ill after a trip to sub-Saharan Africa.

Adolescent↗
PubMed2001

Redox control of AP-1-like factors in yeast and beyond.

Cells have evolved complex and efficient strategies for dealing with variable and often-harsh environments. A key aspect of these stress responses is the transcriptional activation of genes encoding defense and repair proteins. In yeast members of the AP-1 family of proteins are required for the transcriptional response to oxidative stress. This sub-family of AP-1 (called yAP-1) proteins are sensors of the redox-state of the cell and are activated directly by oxidative stress conditions. yAP-1 proteins are bZIP-containing factors that share homology to the mammalian AP-1 factor complex and bind to very similar DNA sequence sites. The generation of reactive oxygen species and the resulting potential for oxidative stress is common to all aerobically growing organisms. Furthermore, many of the features of this response appear to be evolutionarily conserved and consequently the study of model organisms, such as yeast, will have widespread utility. The important structural features of these factors, signaling pathways controlling their activity and the nature of the target genes they control will be discussed.

Animals↗
PubMed2001

Biological action of angiopoietin-2 in a fibrin matrix model of angiogenesis is associated with activation of Tie2.

The endothelial cell (EC) specific tyrosine kinase receptor, Tie2, interacts with at least two ligands, angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2). Ang1 stimulates Tie2 receptor autophosphorylation, while Ang2 has been reported to inhibit Ang1-induced Tie2 receptor autophosphorylation. We studied the effects of Ang1 and Ang2 in an in vitro model of angiogenesis. Human ECs (HUVEC), cultured on 3-D fibrin matrices, were treated with conditioned media (CM) from stably transfected cells expressing human Ang1 or Ang2, or with purified recombinant proteins. EC tube formation was measured as a differentiation index (DI), calculated as the ratio of total tube length over residual of EC monolayer. CM from Ang1 overexpressing A10 SMC or HEK293T cells induced profound HUVEC differentiation, resulting in the formation of extensive capillary-like tubes within 48 h (DI: 24.58+/-5.91 and 19.13+/-7.86, respectively) vs. control (DI: 2.73+/-1.68 and 2.15+/-1.45, respectively, both P<0.001). Interestingly, CM from two independent cell lines overexpressing Ang2 also produced a significant increase in EC differentiation (DI: 9.22+/-3.00 and 9.72+/-4.84, both P<0.005 vs. control) although the degree of angiogenesis was significantly less then that seen with Ang1. Addition of Ang1* (a genetically engineered variant of naturally occurring Ang1) or Ang2 also resulted in dose dependent increases in DI, which were blocked by an excess of soluble Tie2 receptor (20 microg/ml). Both Ang1* and Ang2 induced modest increases in [3H]thymidine incorporation into HUVECs (20 and 26%, respectively), which were inhibited by excess soluble Tie2. Although Ang2 was unable to induce significant Tie2 receptor phosphorylation during a 5-min exposure, a 24-h pretreatment with Ang2, followed by brief re-exposure, produced Tie2 phosphorylation in HUVEC comparable to that produced by Ang1*. These results demonstrate for the first time that Ang2 may have a direct role in stimulating Tie2 receptor signaling and inducing in vitro angiogenesis. Our findings suggest that the physiological role of Ang2 is more complex than previously recognized: acting alternately to promote or blunt Tie2 receptor signaling in endothelial cells, depending on local conditions.

Analysis of Variance↗
PubMed2001

Vacuum metal deposition: factors affecting normal and reverse development of latent fingerprints on polyethylene substrates.

Vacuum metal deposition (VMD) is an established technique for the development of latent fingerprints on non-porous surfaces. VMD has advantages over cyanoacrylate fuming, especially in circumstances where prints are old, have been exposed to adverse environmental conditions, or are present on semi-porous surfaces. Under normal circumstances, VMD produces 'negative' prints as zinc deposits onto the background substrate and not the print ridges themselves. A phenomenon of 'reverse' development, when zinc deposits onto the print ridges and not the background, has been reported by many authors but its causes have not been conclusively identified. Four plastic substrates were used in this study and these could be easily divided into two groups based on the types of development observed as the amount of deposited gold was increased. On group I plastics, identified as low-density polyethylene (LDPE), normal development then reverse development and finally no development resulted with increasing gold. On group II plastics, identified as high-density polyethylene (HDPE), normal development then over-development and finally poor-quality normal development resulted with increasing gold. Our results suggest that the difference between these plastic types causes variations in the gold film structure which in turn dictates the nature of the zinc deposition. On group I plastics, the structure and thickness of the gold film has been identified as the critical factor in the occurrence of normal or reverse development. Thin gold films on plastic substrates form small 'clusters' (or agglomerates) rather than the atoms being uniformly spread over the surface. The size and shape of these clusters is critical. Once the clusters reach a certain morphology, they no longer act as nucleation sites for zinc, and hence, zinc will not deposit onto the substrate. On group II plastics, results suggest that the gold clusters are smaller and more densely packed. Hence, even though the same amount of gold has been deposited, the gold clusters in this case do not reach the critical morphology and so continue to act as nucleation sites for zinc.Typically, zinc will not deposit onto the fingerprint ridges as the gold nucleation sites are buried within the print residue. However, when more gold is deposited, gold emerges at the surface of the latent print allowing zinc deposition onto the ridges. The rate of gold evaporation was found not to affect the structure of the gold film, although a slower rate of evaporation resulted in more effective deposition.

Dermatoglyphics↗
PubMed2001

Muscle free flaps with full-thickness skin grafting: Improved contour over traditional musculocutaneous free flaps.

Occasionally, the aesthetic contour of a musculocutaneous flap can be improved by using the skin paddle as a full-thickness skin graft to cover the free muscle flap. In three patients, traditional musculocutaneous free flap coverage of wounds would have resulted in excess soft tissue bulk. To optimize final contour, the subcutaneous tissue was excised, and the skin replaced as a full-thickness skin graft. Problems with postoperative flap monitoring and skin graft take were not encountered. This technique offers the microsurgeon a simple method to optimize the aesthetic results of composite free tissue transfer.

Adolescent↗
PubMed2001

Carriage of Neisseria meningitidis among household contacts of patients with meningococcal disease in New Zealand.

The aims of this study were to estimate carriage prevalence, identify factors predictive of carriage, and compare strains of Neisseria meningitidis isolated from patients with meningococcal disease and their household contacts. A total of 954 contacts of 160 patients had a nasopharyngeal swab and an interview relating to factors associated with carriage. The carriage prevalence was 20.4% for Neisseria meningitidis, 11.3% for serogroup B, and 2.6% for serogroup C. Age-standardised carriage was higher in Maori (36.8%) than in Pacific Island (21.5%) or European/other (11.1%) ethnic groups. Factors associated with carriage were smoking, with personal smokers (odds ratio [OR] 2.5) and passive smokers (OR 1.6) having a higher carriage risk than those in smoke-free houses; ethnicity, with Maoris having a higher carriage risk than those of non-Maori or non-Pacific Island ethnicity (OR 2.2); gender, with males at higher risk than females (OR 1.7); and age, with 0-4-year-olds less likely and 15-24-year-olds more likely to be carriers than those over 25 years. Strong patient-contact clustering by meningococcal strain (chi-square1 = 16.7, P=0.00004) suggested an important role for the household setting in transmission. The low carriage prevalence of serogroup B Neisseria meningitidis among household contacts may reflect its low transmissibility but high virulence. No direct relationship was found between prevalence of ethnic-specific carriage and the incidence of meningococcal disease.

Adolescent↗
PubMed2001

A prospective randomised study of laser reshaping of cartilage in vivo.

Laser reshaping using low laser energy levels was performed on the cartilage of ten porcine ears. The ears were examined up to 4 months after laser reshaping and the stability of the reshaping was assessed by photography and casts obtained from alginate impressions of the ears. The cartilage was also studied histologically in three animals at 3 weeks, 8 weeks, and 4 months using haematoxylin and eosin (H&E), periodic-acid-Schiff (PAS) and alcian blue stains as well as Mib-1 antibody stain to detect cells in cycle. These ears were compared with the other control or non-irradiated ear. All the treated ears initially demonstrated a controlled alteration in their shape. Four were exposed to a pulse energy of 2 J/cm2 at 20 Hz with a spot diameter of 1.1 mm for 7 s and retained their shape for up to 14 days. However, the three exposed to the same levels of energy for 9 s showed tissue necrosis whereas the three which were treated for less than 4 s returned to their original shape after 24 h. Histological examination revealed that there was a dramatic eccentric proliferation of perichondrium away from the centre of irradiation with a noticeable absence of any inflammation. In all laser-irradiated areas there was a loss of staining with PAS and a dramatic increase in staining with alcian blue within the cartilage matrix. Viable chondrocytes were absent from the irradiated cartilage. Staining with a Mib-1 antibody that detects cells in cycle showed positive staining in a small fraction of proliferated perichondrial cells where new cartilage had been produced.

Animals↗
PubMed2001

HBP2: a new mammalian protein that complements the fission yeast MBF transcription complex.

The mammalian HBP2 gene has been isolated by functional complementation of cells unable to undergo DNA replication in fission yeast. HBP2 is a protein with a high mobility group (HMG) domain that belongs to the Sox (Sry-related HMG box) family of transcription factors. As in other members of the family, the HMG box in HBP2 is a DNA-binding domain that is essential for its function in Schizosaccharomyces pombe. Expression of HBP2 in fission yeast activates CdclO-dependent transcription at G1/S and allows growth of cdc10-129, resldelta and rep2delta mutant cells at the restrictive temperature. The mammalian HBP2 activates transcription at G1/S in the fission yeast Sch. pombe.

Amino Acid Sequence↗
PubMed2001

Influence of circadian phase and test illumination on pre-clinical models of anxiety.

Pre-clinical models of anxiety, particularly the elevated plus-maze (EPM), have been shown to be sensitive to a variety of methodological variations. Recent research has implicated circadian phase of testing in influencing the behavioural profile of 5-HT(1A) ligands on the EPM. The present study investigated the effects of testing animals during the dark and light phases and in light and subjective dark test conditions on baseline behaviour in animal models of anxiety. Eighty singly housed male Sprague-Dawley rats were exposed to a battery of unconditioned, exploratory tests (EPM, open field arena, holeboard) and a new model of extreme anxiety, the unstable elevated exposed plus-maze (UEEPM). Circadian phase of testing failed to consistently alter behaviour on any model. Level of test illumination had no effect on subjects' response to the open field arena, holeboard or UEEPM. Dark testing increased locomotor activity on the EPM (total arm entries, closed arm entries and distance moved) without decreasing open-arm avoidance. The construct of anxiety as measured by a number of different paradigms withstood major intra-laboratory manipulation of circadian phase of testing and illumination of apparatus. It is suggested that the effects of circadian rhythmicity may be confined to the behavioural profiles of serotonergic, particularly 5-HT(1A), ligands on the EPM.

Animals↗
PubMed2001

Evaluating psychological debriefing: are we measuring the right outcomes?

The efficacy of critical incident stress debriefing (CISD) and psychological debriefing (PD) following potentially traumatising events has recently been challenged after a number of recent randomised controlled trials (RCTs) failed to demonstrate that CISD or PD prevents or reduces the incidence of posttraumatic stress disorder (PTSD). These studies have used measures of PTSD as the principal outcome and have generally not measured comorbid psychopathology, behavioral or social dysfunction. In a recent RCT of group debriefing amongst British soldiers returning from peacekeeping operations in Bosnia, PD had a significant effect in reducing a worrying level of alcohol misuse in the sample. The findings of this study suggest that that it is premature to conclude that debriefing is ineffective and that a broader range of outcome measures should be employed in future trials of debriefing.

Adult↗
PubMed2001

Tie receptors: new modulators of angiogenic and lymphangiogenic responses.

Angiogenesis is required for normal embryonic vascular development and aberrant angiogenesis contributes to several diseases, including cancer, diabetes and tissue ischaemia. What are the molecular mechanisms that regulate this important process? The Tie family of receptors and their ligands, the angiopoietins, are beginning to provide insight into how vessels make decisions such as whether to grow or regress--processes that are important not only during development but throughout an organism's life.

Aging↗
PubMed2001

Oxygen or air?

Explore the source record for details and available documents.

Air↗
PubMed2001

Economic assessment of rheolytic thrombectomy versus intracoronary urokinase for treatment of extensive intracoronary thrombus: Results from a randomized clinical trial.

BACKGROUND: Despite advances in mechanical and pharmacologic therapy, thrombus-containing lesions are at high risk for adverse events and remain a challenging subset for percutaneous coronary revascularization. Recently, rheolytic thrombectomy with the AngioJet device has been shown to safely remove intracoronary thrombus, but the overall cost-effectiveness of this technique is unknown. METHODS: We determined in-hospital and 1-year follow-up costs for 349 patients with overt intracoronary thrombus who were randomly assigned to treatment with intracoronary urokinase (6- to 30-hour infusion followed by definitive revascularization; n = 169) or immediate thrombectomy with the AngioJet device (n = 180) as part of the Vein Graft AngioJet Study (VeGAS) 2 trial. Catheterization laboratory costs were based on measured resource utilization and 1998 unit costs, whereas all other costs were estimated from hospital charges and cost center-specific cost-to-charge ratios. RESULTS: Compared with urokinase, rheolytic thrombectomy reduced the incidence of periprocedural myocardial infarction (12.8% vs 30.3%, P <.001) and major hemorrhagic complications (2.8% vs 11.2%, P <.001) and shortened length of stay by nearly 1 day (4.2 vs 4.9 days; P =.02). As a result, AngioJet treatment reduced procedural costs, hospital room/nursing costs, and ancillary costs with resulting hospital cost savings of approximately $3500 per patient during the initial hospitalization ($15,311 vs $18,841, P <.001). These cost savings were maintained at 1 year of follow-up ($24,389 vs $29,109, P <.001). CONCLUSIONS: Compared with standard treatment with intracoronary urokinase, rheolytic thrombectomy both improves clinical outcomes and reduces overall medical care costs for patients with extensive intracoronary thrombus.

Angioplasty, Balloon, Coronary↗
PubMed2001

Prospective randomized, double-blind comparative study of dexamethasone, ondansetron, and ondansetron plus dexamethasone as prophylactic antiemetic therapy in patients undergoing day-case gynaecological surgery.

Dexamethasone alone and in combination with selective 5-hydroxytryptamine receptor antagonists is of benefit in the prophylaxis of post-operative nausea and vomiting. In this study, the effectiveness of such a combination in comparison to either drug alone is investigated in day case gynaecological surgery. A total of 177 patients were randomized to three treatment groups: dexamethasone 8 mg, ondansetron 4 mg, and dexamethasone 8 mg plus ondansetron 4 mg. The only significant difference between groups was seen in the first 3 h when failure of prophylaxis was more frequent in patients who had received dexamethasone alone (P=0.0085; Fisher's exact probability test). Confidence interval analysis indicates a modest treatment effect for the combination and the decision whether to perform a larger study depends upon whether such an effect is clinically relevant.

Adult↗
PubMed2001

Rescue of the early vascular defects in Tek/Tie2 null mice reveals an essential survival function.

Disruption of the signaling pathways mediated by the receptor tyrosine kinase Tek/Tie2 has shown that this receptor plays a pivotal role in vascularization of the developing embryo. In this report, we have utilized the tetracycline-responsive binary transgenic system to overcome the early lethal cardiovascular defects associated with the tekDeltasp null allele in order to investigate the role of Tek in later stages of vessel growth. We show for the first time in vivo that synchronized loss of tek expression correlates with rapid endothelial cell apoptosis in hemorrhagic regions of the embryo, demonstrating an ongoing requirement for Tek-mediated signal transduction in vascular maintenance.

Actins↗