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Biomedical subjects

N Jones

Publications and source records attributed to N Jones.

At least 109 records · Page 6Linked to original sources
PubMed1999

After the internal market: public ownership or poisoned chalice?

This article examines the reasons why the internal market failed to gain public acceptance and looks beyond the popular view which argued the non-acceptance was a result of the "two tier" service and increased bureaucracy. It compares the experience of customers in the internal market with those of other public services that have undergone privatization. The article concludes that differences in the range and pattern of the services provided by the NHS led the public to a lower level of understanding regarding improvements and efficiency. The benefits of the market in other once public services were more transparent and there were greater incentives to accept the change. The article recommends that the clinicians involved in the management of primary care groups should learn the lessons of the internal market because users are ill-equipped for the next stage of healthcare reform as they were for the last.

Attitude to Health↗
PubMed1999

Intrusive and withdrawn behaviours of mothers interacting with their infants and boyfriends.

Investigated stability and change in intrusive and withdrawn interaction behaviours of 23 mothers in Study 1 and 31 mothers in Study 2. Comparisons between mother-infant and mother-boyfriend interactions revealed that mothers who had been withdrawn with their infants were quiet, bored-looking, physically distant, and underinvolved with their boyfriends. Mothers who had been intrusive with their infants were verbally sharp and controlling with their boyfriends. These findings suggested stability across social contexts. Comparing maternal responding to instructions to think about themselves (self-focus) or their infants (infant-focus) revealed that infant-focusing attenuated intrusive behavior among intrusive mothers and self-focusing attenuated negative affect among withdrawn mothers. These findings suggested that cognitive focusing ameliorates nonoptimal maternal behaviours and has differential effects on intrusive and withdrawn mothers.

Adult↗
PubMed1999

The significance of an 'insufficient' Pipelle sample in the investigation of post-menopausal bleeding.

BACKGROUND: Out-patient endometrial sampling is a commonly performed procedure in the investigation of post-menopausal bleeding. We hypothesized that an 'insufficient' Pipelle sample reliably reflected the absence of serious endometrial pathology. METHODS AND RESULTS: A review of 141 consecutive cases reported as 'insufficient' for diagnostic purposes revealed 29 (20%) cases to have uterine pathology after secondary investigation. These included two cases of endometrial carcinoma and two other cases of uterine malignancy. CONCLUSION: These results do not support the initial hypothesis and suggest that in women presenting with post-menopausal bleeding, an 'insufficient' sample is an indication for further investigation.

Biopsy↗
PubMed1998

The impact of HIV on Streptococcus pneumoniae bacteraemia in a South African population.

OBJECTIVES: To determine the impact of HIV infection on Streptococcus pneumoniae bacteraemia in adults and children by analysing the prevalence and clinical features of such diseases and determining the prevalent serotypes/serogroups and susceptibility patterns of isolates. DESIGN: Patients were identified prospectively from January to October 1996. SETTING: Chris Hani Baragwanath Hospital, Soweto, a tertiary referral hospital treating adults and children, in an urban district near Johannesburg, South Africa. PATIENTS AND METHODS: All patients with S. pneumoniae isolated from blood culture by the Microbiology Department, Chris Hani Baragwanath Hospital were studied. Clinical and microbiological features were recorded. RESULTS: A total of 178 patients with S. pneumoniae were investigated as part of the study; 49 were aged < 13 years. HIV seroinfection was present in 25 (51%) children and 58 (45%) adults. The incidence of S. pneumoniae bacteraemia was 36.9-fold increased in HIV-seropositive children and 8.2-fold increased in HIV-seropositive adults compared with HIV-seronegative individuals. Both adult and paediatric HIV-seropositive patients with S. pneumoniae bacteraemia were significantly younger than HIV-seronegative patients. Pneumonia was a significantly more common presentation in HIV-seropositive children, otherwise the spectrum of disease and outcome were similar in HIV-seronegative and positive groups. Serotype 1 S. pneumoniae isolates were significantly less common in HIV-infected individuals (both adults and children). Resistance to penicillin was increased in S. pneumoniae isolates from HIV-infected patients (significant in adults). Patients with penicillin-resistant isolates did not have a poorer outcome. The potential coverage of serotypes/serogroups included in the proposed nine-valent conjugate pneumococcal vaccine was 88% in HIV-seronegative children and 83% in HIV-seropositive children. The potential coverage of the currently available 23-valent pneumococcal vaccine for adults was 98.2 and 100)% for HIV-infected and HIV-uninfected adults, respectively. CONCLUSION: The burden of bacteraemia due to S. pneumoniae in HIV-seropositive individuals admitted to our hospital is considerable. Differences in the S. pneumoniae serotypes/serogroups in HIV-infected patients have been demonstrated with resultant differences in antibiotic susceptibility patterns. Excellent potential for vaccine coverage was demonstrated for both HIV-seronegative and HIV-seropositive individuals. Further studies are necessary to test the clinical efficacy of pneumococcal vaccination of HIV-seropositive adults and children as a potential preventative measure against this prevalent disease.

Adolescent↗
PubMed1998

The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R.

Tek/Tie2 is an endothelial cell-specific receptor tyrosine kinase that has been shown to play a role in vascular development of the mouse. Targeted mutagenesis of both Tek and its agonistic ligand, Angiopoietin-1, result in embryonic lethality, demonstrating that the signal transduction pathway(s) mediated by this receptor are crucial for normal embryonic development. In an attempt to identify downstream signaling partners of the Tek receptor, we have used the yeast two-hybrid system to identify phosphotyrosine-dependent interactions. Using this approach, we have identified a novel docking molecule called Dok-R, which has sequence and structural homology to p62dok and IRS-3. Mapping of the phosphotyrosine-interaction domain within Dok-R shows that Dok-R interacts with Tek through a PTB domain. Dok-R is coexpressed with Tek in a number of endothelial cell lines. We show that coexpression of Dok-R with activated Tek results in tyrosine phosphorylation of Dok-R and that rasGAP and Nck coimmunoprecipitate with phosphorylated Dok-R. Furthermore, Dok-R is constitutively bound to Crk presumably through the proline rich tail of Dok-R. The cloning of Dok-R represents the first downstream substrate of the activated Tek receptor, and suggests that Tek can signal through a multitude of pathways.

3T3 Cells↗
PubMed1998

Regulation of the fission yeast transcription factor Pap1 by oxidative stress: requirement for the nuclear export factor Crm1 (Exportin) and the stress-activated MAP kinase Sty1/Spc1.

The fission yeast Sty1 stress-activated MAP kinase is crucial for the cellular response to a variety of stress conditions. Accordingly, sty1- cells are defective in their response to nutrient limitation, lose viability in stationary phase, and are hypersensitive to osmotic stress, oxidative stress, and UV treatment. Some of these phenotypes are caused by Sty1-dependent regulation of the Atf1 transcription factor, which controls both meiosis-specific and osmotic stress-responsive genes. However, in this report we demonstrate that the cellular response to oxidative stress and to treatment with a variety of cytotoxic agents is the result of Sty1 regulation of the Pap1 transcription factor, a bZip protein with structural and DNA binding similarities to the mammalian c-Jun protein. We show that both Sty1 and Pap1 are required for the expression of a number of genes involved in the oxidative stress response and for the expression of two genes, hba2+/bfr1+ and pmd1+, which encode energy-dependent transport proteins involved in multidrug resistance. Furthermore, we demonstrate that Pap1 is regulated by stress-dependent changes in subcellular localization. On imposition of oxidative stress, the Pap1 protein relocalizes from the cytoplasm to the nucleus in a process that is dependent on the Sty1 kinase. This relocalization is the result of regulated protein export, rather than import, and involves the Crm1 (exportin) nuclear export factor and the dcd1+/pim1+ gene that encodes an Ran nucleotide exchange factor.

Activating Transcription Factor 1↗
PubMed1998

An ultrahigh-vacuum chamber for surface X-ray diffraction.

An ultrahigh-vacuum environmental chamber for surface X-ray diffraction on Station 9.4 at the Synchrotron Radiation Source, Daresbury Laboratory, is described. Film growth can be monitored by simultaneously recording the Auger signal and the X-ray intensity at a particular point in reciprocal space. Such in situ measurements are essential for understanding the dynamic processes that occur during adsorption. An example is given in which the specularly reflected X-ray signal is correlated with Auger plots, during growth of Tl on Cu(001). In addition, the diffractometer and chamber combination allow large reconstructions to be investigated as shown by the in-plane structural analysis of the c(4x4) InSb surface. A study of the layer structure of Cr on Ag(001), in which an extended out-of-plane detector assembly was used, is also presented.

Journal Article↗
PubMed1998

p300 and ATF-2 are components of the DRF complex, which regulates retinoic acid- and E1A-mediated transcription of the c-jun gene in F9 cells.

Transcriptional activation of the c-jun gene is a critical event in the differentiation of F9 cells. In our previous studies we characterized an element [differentiation response element (DRE)] in the c-jun promoter that is both necessary and sufficient to confer the capacity for differentiation-dependent up-regulation. This element binds the differentiation regulatory factor (DRF) complex, of which one component is the adenovirus E1A-associated protein p300. We have now identified activation transcription factor-2 (ATF-2) as a DNA-binding subunit of the DRF complex. p300 and ATF-2 interact with each other in vivo and in vitro. The bromodomain and the C/H2 domain of p300 mediate the binding to ATF-2, which in turn requires a proline-rich region between amino acids 112 and 350 for its interaction with p300. The phosphorylation of the serine residue at position 121 of ATF-2 appears to be induced by protein kinase C alpha (PKC alpha) after treatment of cells with retinoic acid (RA) or induction with E1A. In cotransfection assays, wild-type ATF-2 enhanced the transcription of an E2/tk-luciferase construct, in conjunction with p300-E2. However, a mutant form of ATF-2 with a mutation at position 121 (pCMVATF-2(Ser121-Ala)) did not. These results suggest that ATF-2 and p300 cooperate in the control of transcription by forming a protein complex that is responsive to differentiation-inducing signals, such as RA or E1A, and moreover, that the phosphorylation of ATF-2 by PKC alpha is probably a signaling event in the pathway that leads to the transactivation of the c-jun gene in F9 cells.

Activating Transcription Factor 2↗
PubMed1998

Diffuse neuronal perikaryon amyloid precursor protein immunoreactivity in a focal head impact model.

Amyloid precursor protein (APP) has been shown to accumulate in traumatically injured axons as early as 1 hour after injury. This accumulation may be due to interruption of fast axoplasmic transport and/or upregulation of APP synthesis. The aim of this study was to examine the neuronal cell body response to head impact using APP immunostaining in a focal non-missile head impact model. Ten anaesthetised and ventilated 2 year old Merino ewes were subjected to graded impact in the left temporal region by captive bolt. 2 hours after impact the brain was perfused fixed with formaldehyde. The tissue was mounted in paraffin, sectioned and stained with a monoclonal antibody to APP and standard H&E stain. APP positivity was semi-quantitated using a modification of our previously described sector scoring system [1]. Widespread neuronal APP positivity was found in the cerebral hemispheres and brain stem distant from the site of focal injury in all 10 animals. The most prominent APP positivity was found in the nerve cell bodies of the impacted left cerebral hemisphere. APP positive neurons were also found within regions which were structurally normal when stained with H&E. These results demonstrate diffuse neuronal perikaryon APP immunoreactivity following a focal head impact injury. The expression of APP within the neuronal cell body may be due to upregulation of APP synthesis or alterations in the availability of epitopes of APP. Further studies are in progress to address these hypotheses.

Amyloid beta-Protein Precursor↗
PubMed1998

Lack of correlation between vacuolating cytotoxin activity, cagA gene in Helicobacter pylori, and peptic ulcer disease in children.

To determine the prevalence of the cagA gene and vacuolating cytotoxin in Helicobacter pylori isolates obtained from children and to characterize the relationship between cagA, cytotoxin production, and ulcerogenesis, pediatric Helicobacter pylori isolates were tested for cagA by the polymerase chain reaction and for vacuolating cytotoxin by a cell culture assay. Helicobacter pylori isolates were obtained from 33 children referred for upper gastrointestinal endoscopy. Twenty-six of these isolates were tested for cagA by the polymerase chain reaction; all 26 (100%) were positive. Of the 26 children from whom these isolates were obtained, 26 (100%) had chronic gastritis and 12 (46%) had duodenal ulcers. Nine (30%) of 30 isolates tested showed expression of vacuolating cytotoxin, only three of which came from patients with duodenal ulceration (odds ratio 0.81, 95% confidence interval 0.1-5.3). Of the 23 cagA-positive isolates tested for cytotoxin, only nine (39%) were positive. There was no association between vacuolating cytotoxin and clinical symptoms, nor was cytotoxicity associated with ulcerogenesis. In summary, the findings suggest that cagA is not a marker of duodenal ulceration or of vacuolating cytotoxin production in children referred for endoscopy.

Adolescent↗
PubMed1998

Early development of synchronized walking on the rotorod in rats. Effects of training and handling.

There is considerable improvement of motor coordination on the rotorod during the first 3 weeks of development in rats. The purpose of the present study was to determine some factors implicated in this improvement. From days 15-22 of age, rats were: (1) extensively trained on the rotorod; (2) minimally trained on the rotorod; (3) handled daily but not trained on the rotorod; and (4) neither handled nor trained. All animals were tested on the rotorod on day 23, with separate groups of the naive rats also being tested on days, 19, 20, 21 or 22. Latencies before falling and the percentage of time spent walking in time to the movement of the rotating rod were recorded. There was a close correspondence between these two scores during ontogeny. The percentage of time spent walking was similar among extensively trained, minimally trained, and handled rats and significantly higher than that measured in rats tested only on 1 day. These results indicate that the emergence of this postural sensorimotor skill is more dependent on the maturation of sensorimotor brain region than on previous training on the apparatus.

Aging↗
PubMed1998

Stress-activated signalling pathways in yeast.

Eukaryotic cells have developed response mechanisms to combat the harmful effects of a variety of stress conditions. In the majority of cases, such responses involve changes in the gene expression pattern of the cell, leading to increased levels and activities of proteins that have stress-protective functions. Over the last few years, considerable progress has been made in understanding how stress-dependent transcriptional changes are brought about, and it transpires that the underlying mechanisms are highly conserved, being similar in organisms ranging from yeast to man. Many of the stress signals derive from the extracellular environment and accordingly these signals require transduction from the cell surface to the nucleus. This is accomplished through stress-activated signalling pathways, key amongst which are the highly conserved stress-activated MAP kinase pathways. Stimulation of these pathways leads to the increased activity of specific transcription factors and consequently the increased expression of certain stress-related genes. In this review, we focus on the progress that has been made in understanding these stress responses in yeast.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1998

Facial growth in Cercocebus torquatus: an application of three-dimensional geometric morphometric techniques to the study of morphological variation.

This paper presents a study of 3-dimensional growth in the facial skeleton of the mangabey, Cercocebus torquatus. The pattern of facial cortical remodelling in this species is already well mapped from an earlier study. In this paper we consider the extent to which these remodelling maps relate to ontogenetic changes in size and shape of the face. This study is based on 31 facial landmarks taken from 49 adult and subadult faces. Our analysis draws on some of the tools of geometric morphometrics and we take this opportunity to describe our implementation of these tools for 3D data. The geometric analysis permits the known remodelling maps to be interpreted in the context of the general pattern of facial growth in this species. We are also able to examine sexual dimorphism in the face of this species and consider the extent to which males and females share similar ontogenetic allometries. Our findings indicate that the general pattern of size-related shape variation during facial growth is more or less identical for males and females up to eruption of the third permanent maxillary molar (M3). After this, ontogenetic allometries appear to diverge. The finding of a common growth allometry that is well approximated for younger specimens by a simple linear model is consistent with the earlier findings of a consistent pattern of facial remodelling up to M3 eruption. We consider the implications of these findings in terms of the potential for these approaches in the study of comparative growth in related species.

Animals↗
PubMed1998

Widespread axonal injury in gunshot wounds to the head using amyloid precursor protein as a marker.

In order to determine whether axonal injury (AI) is a factor in cases of penetrating head injury, the brains of 14 patients who died shortly after sustaining a fatal gunshot wound (GSW) to the head were examined, and the presence of AI determined using immunohistochemical staining for amyloid precursor protein (APP). The distribution of AI was mapped throughout the cerebral hemispheres and brain stem. AI was present in all cases in a diffuse distribution distant to the missle track with severe involvement of the brain stem in all cases. There was no axonal APP immunoreactivity in the direct region of the missle track at the point of primary axotomy. The APP-positive AI in these cases is likely to be a mixture of primary and secondary AI as APP immunostaining is unable to distinguish primary AI due to mechanical deformation from AI secondary to hypoxic-ischemic damage.

Adolescent↗