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Biomedical subjects

N Jones

Publications and source records attributed to N Jones.

At least 163 records · Page 9Linked to original sources

Meningococcal disease epidemiology and control in New Zealand.

Epidemiology, surveillance and research New Zealand has a high quality surveillance system for meningococcal disease that successfully integrates notification and laboratory data. Since 1991, New Zealand has had elevated incidence rates of meningococcal disease rising to 6.2 per 100,000 population in 1994. This represents a rate that is four times that recorded in 1989/90. Serogroup B infection predominates and international experience suggests that these elevated rates may continue for 5 to 15 years. Rates of meningococcal disease in Maori and Pacific Islands populations were three times higher than in Europeans at 10.0 and 12.3 per 100,000 respectively in 1994. The rates were particularly high for infants with the rate in Maori infants under 1 year reaching 120 per 100,000. The case fatality rate at 5.3% for 1994 would appear to be relatively low by international standards. Case control studies could be used to investigate potentially modifiable primary risk factors for disease. Intensive case review studies to investigate the role of such factors as preadmission antibiotics in reducing severe outcomes may be of benefit. The Ministry of Health or research funding organisations should consider the potential value of such studies in more detail.

Adolescent↗

ATF-2 contains a phosphorylation-dependent transcriptional activation domain.

The ATF-2 transcription factor can mediate adenovirus E1A-inducible transcriptional activation. Deletion analysis has indicated that the N-terminal region of ATF-2 is essential for this response. Furthermore, the N-terminus can activate transcription in the absence of E1A when fused to a heterologous DNA binding domain. However, in the intact protein this activation domain is masked. In this report we show that residues in the N-terminus required for activation are also required for mediating E1A stimulation. In particular two threonine residues at positions 69 and 71 are essential. These residues are phosphorylated in vivo and can be efficiently phosphorylated in vitro by the JNK/SAPK subgroup of the MAPK family. ATF-2 can bind to a UV-inducible kinase through a region in the N-terminus that is distinct from the sites of phosphorylation; this binding region is both necessary for phosphorylation by JNK/SAPK in vitro and for transcriptional activation in vivo. The activity of the N-terminus is stimulated by UV irradiation which stimulates the signalling pathway leading to JNK/SAPK. Finally, although ATF-2 binds to the E1A protein, the N-terminal activation domain is not required for this interaction. The results show that ATF-2, like other members of the ATF/CREB family of DNA binding proteins is regulated by specific signalling pathways.

Activating Transcription Factor 2↗

Role of preoperative and postoperative sensorimotor training on restoration of the equilibrium behavior in adult mice following cerebellectomy.

The equilibrium behavior of cerebellectomized C57/BL6 adult mice was studied on a rota rod rotating at 20 revolutions per minute and the influence of preoperative or/and postoperative training on restoration of equilibrium capabilities investigated. The duration of the preoperative training was either short (1 day) or long (7 days). The postoperative training began either the day after cerebellectomy or was delayed by 7 days. The results demonstrate that postoperative training was efficient in restoring the equilibrium behavior in all cases, except for the animals which were trained for a long period (7 days) before the lesion. Preoperative training was also efficient providing it was long enough (7 days), except for the animals which postoperative training began the day after cerebellectomy. It can be stated that both preoperative and postoperative trainings influence the restoration of the equilibrium following a cerebellectomy and that, in some instances, preoperative training can be as efficient as postoperative.

Animals↗

Experimental infection of human nasal mucosal explants with Neisseria meningitidis.

The interaction of Neisseria meningitidis with rhinopharyngeal epithelium was studied by experimental infection of explants of human nasal turbinate mucosa with two wild strains: a fully capsulate case isolate, and an epidemiologically related non-capsulate nasopharyngeal isolate. After incubation for 4 h, epithelial cells of infected explants changed conformation from tall columnar morphology towards cuboidal, and there was increased discharge of mucus globules from goblet cells. By 24 h there was significant damage to infected epithelia, including projection of cells out of the surface, cytoplasmic blebbing and mitochondrial abnormalities. Meningococci were associated with surface non-ciliated cells by 4 h after infection. By 24 h after infection they were associated extensively with all cell types exhibiting damage. There was little association with secreted mucus. In areas of cell damage, penetration between surface cells was observed. Endocytosis into non-ciliated cells was observed in only a minority of explants studied and only in those infected for 24 h. From this intracellular site there was apparent migration to adjacent cells and to intercellular locations. No organisms were observed within or beneath basement membrane collagen in any explants but internalisation into mononuclear phagocytes was observed occasionally.

Cilia↗

Taped imaginal exposure as a treatment for post-traumatic stress reactions.

The efficacy of taped imaginal exposure as a treatment for Post-Traumatic Stress Reactions (PTSR) was assessed in eighteen consecutive outpatients, including Gulf War veterans. Detailed present-tense scripts of their personal traumatic experiences were prepared and in all but two cases audio-taped and listened to regularly. The severity of PTSR and standard questionnaire scores (including the IES, BDI, GHQ8 and the SCL 90) all showed statistically significant improvements post treatment and at three month follow-up. This case series confirms the potential efficacy of taped imaginal exposure in the treatment of full and partial forms of Post-Traumatic Stress Disorder (PTSD). The simplicity of its administration and acceptability to the individual suggest that it is worthy of more thorough research.

Adult↗

Heartsink patients: a study of their general practitioners.

BACKGROUND: A number of attempts have been made to investigate the heartsink, difficult, dysphoric or problem patient. Most studies have emphasized the role which the patient plays in evoking despair, anger and frustration in the doctor. However, one doctor's list of difficult patients may not necessarily be the same as another's. AIM: A study was undertaken to determine if the individual characteristics of general practitioners are associated with the number of heartsink patients they report on their patient lists. METHOD: Sixty out of 137 urban general practitioners drawn at random from the Sheffield Family Health Services Authority list were surveyed by structured interview and questionnaires in 1990. Outcome measures were interview data and scores on the 12-item general health questionnaire, Warr-Cook-Wall job satisfaction scale and the Bortner personality profile measure. RESULTS: Sixty per cent of the variance in the number of heartsink patients that general practitioners reported on their lists could be accounted for by the following four explanatory variables: greater perceived workload; lower job satisfaction; lack of training in counselling and/or communication skills; and lack of appropriate postgraduate qualifications. No other variables considered could account for the variance in the number of heartsink patients reported by general practitioners. CONCLUSION: The individual characteristics of doctors are associated with the number of heartsink patients reported by general practitioners. To reduce the number of such patients experienced, it may be necessary for general practitioners to reduce their workload and increase their job satisfaction and their level of relevant postgraduate training.

Attitude of Health Personnel↗

Nitric oxide donors inhibit platelet spreading on surfaces coated with fibrinogen but not with fibronectin.

We have studied the effect of nitric oxide (NO) on the interaction of washed human platelets with fibrinogen or fibronectin adsorbed on glass. Platelet contacts were visualized by interference reflection microscopy at 37 degrees C in Tyrode's solution. The areas of spread platelets were measured, using digital video image processing techniques, at times up to 30 minutes after initial surface platelet contact. On fibrinogen spreading was inhibited by NO donors in the order of potency: S-nitroso-acetylpenicillamine > sodium nitroprusside > S-nitroso-glutathione. The inhibitory action of NO donors was prevented by Oxy-haemoglobin, confirming that this inhibition was due to the release of NO. In contrast, NO donors had virtually no effect on platelet spreading on fibronectin. Platelet adhesion to fibrinogen is mediated by GP IIb IIIa and the vitronectin receptor (VNR), while that to fibronectin is via GP IIb IIIa, VNR, Ic IIa and VLA-6. Our results thus indicate that NO inhibits adhesion mediated by GP IIb IIIa and/or VNR but not by the two other receptors. The mechanism of this receptor-specific inhibition of platelet adhesion remains to be elucidated.

Adsorption↗

Effect of administration of 3-acetylpyridine followed by niacinamide injection on survival, extent of the inferior olivary complex lesion, and response to harmaline in the young rat.

In the 15 day-old DA/HAN strained rat, i.p. injection of 3-acetylpyridine (3-AP) 50, 65 or 95 mg.kg-1 was followed 2 to 4 hours later by administration of niacinamide (300 mg.kg-1). The percentage of survival and the extent of the inferior olivary complex (IOC) lesion, determined histologically, were correlated with both the dose of 3-AP administered and the time delay between 3-AP and niacinamide injections. Moreover, the tremor elicited by harmaline was also correlated with the extent of the IOC lesion. The results show that it is more advantageous to administer 95 mg.kg-1 3-AP and to delay niacinamide injection by 2h30 or less to get the higher percentage of survival (about 90%) and a reasonably high percentage of totally IOC lesioned rats (more than 30%). They also demonstrate that the harmaline test is not sufficient to acutely judge of the extent of the IOC lesion and that, in all cases, histological controls have to be done. The results are discussed in terms of interrelationships of the variable studied.

Animals↗

Phosphorylation of E2F-1 modulates its interaction with the retinoblastoma gene product and the adenoviral E4 19 kDa protein.

The transcription factor E2F is regulated through its cyclical interaction with a spectrum of cellular proteins. One such protein is the product of the retinoblastoma gene (Rb); association of E2F with Rb inhibits its transactivation potential. However, in adenovirus-infected cells, E2F is complexed to the 19 kDa product of the adenovirus E4 gene. We have studied the interaction of E2F-1 with the Rb and adenovirus E4 proteins and show that phosphorylation of E2F-1 on serine residues 332 and 337 prevented its interaction with Rb but was a prerequisite for interaction with E4. These residues were phosphorylated in vivo and by p34cdc2 kinase in vitro. Upon stimulation of serum-starved cells, phosphorylation was induced in the late G1 phase of the cell cycle. These observations suggest that phosphorylation of E2F-1 is important in the regulation of its activity during the cell cycle and during infection of cells by adenovirus.

Adenoviridae Infections↗

pct1+, which encodes a new DNA-binding partner of p85cdc10, is required for meiosis in the fission yeast Schizosaccharomyces pombe.

The transcriptional activation of genes at late G1 is an important regulatory step in the commitment to a new cell division cycle. In Schizosaccharomyces pombe, this regulation is mediated by MCB elements that serve as binding sites for the MBF/DSC-1 complex. The cdc10(+)-encoded protein is a component of this complex. We report the cloning of a new gene, pct1+, encoding a 73-kD protein that interacts with p85cdc10 to form an MCB-binding heteromer. Pct1+ is related to, but distinct from, the res1+/sct1+ gene that also encodes a p85cdc10 partner. p73pct1 has centrally located ankyrin repeats and a putative amino-terminal DNA-binding domain that has extensive sequence similarity to the DNA-binding domains of the Saccharomyces cerevisiae SWI4 and MBP1 proteins. The p73pct1/p85cdc10 complex binds both in vitro and in vivo to MCB but not SCB or E2F sites. Overexpression of pct1+ is sufficient to rescue the growth of the cdc10-129 temperature-sensitive mutant at the restrictive temperature, although it is unable to rescue a cdc10 null mutation. A deletion of pct1+ is not lethal but does result in a severe meiotic defect. Our results indicate that there are two cdc10-containing heteromeric complexes that bind to MCB elements and play differential roles in mitotic division and meiosis.

Amino Acid Sequence↗

YAP1 dependent activation of TRX2 is essential for the response of Saccharomyces cerevisiae to oxidative stress by hydroperoxides.

The role of the YAP1 transcription factor in the response of Saccharomyces cerevisiae cells to a variety of conditions that induce oxidative stress has been investigated. Cells deficient in YAP1 were found to be hypersensitive to hydroperoxides and thioloxidants, whereas overexpression of YAP1 conferred hyper-resistance to the same conditions. These treatments resulted in an increase in YAP1-specific binding to DNA together with an increase in YAP1 dependent transcription. Our results indicate that this increase is not due to an increase in synthesis of YAP1 protein, but rather results from modification of pre-existing protein. Using a specific genetic screen, the TRX2 gene, one of two genes of S. cerevisiae that encode thioredoxin protein, was identified as being essential for YAP1 dependent resistance to hydroperoxides. Furthermore, efficient expression of TRX2 was dependent on YAP1 and enhanced under conditions of oxidative stress.

Base Sequence↗

Clustering of human T lymphotropic virus type I seropositive in Montserrat, West Indies: evidence for an environmental factor in transmission of the virus.

A community survey of human T cell lymphotropic virus type I (HTLV-I) in Montserrat, West Indies, identified 22 instances in which 2 HTLV-I-seropositive adults lived within 60 m of each other (close pairs), compared with 7.8 expected (P < .001). Five of these close pairs were mother-offspring or husband-wife. The remaining 17 pairs were of unrelated members in separate households. The percentages of male-female (41%), female-female (41%), and male-male (18%) types in these 17 pairs were very similar to those among the 1377 similarly defined pairs in which neither or only 1 member was seropositive, affording no support for extramarital heterosexual activity as an explanation for the clustering observed. Thus, the demography of HTLV-I was not accounted for completely by sexual and mother-to-offspring transmission. The predominance of clustering of unrelated HTLV-I-seropositive individuals in locations with high mosquito infestation raised the possibility of sporadic transmission of HTLV-I by hematophagous insects.

Adolescent↗

Audit of telephone advice in a paediatric accident and emergency department.

This paper audits the telephone requests for advice to a paediatric accident and emergency (A&E) Department over a 4-week period. All calls were answered by senior nurses. Most calls were received in the early evenings when the A&E department was busy. Parents were the most frequent callers and the majority of calls were for children under 5 years of age. The problems presented were wide ranging but advice over the telephone meant that many unnecessary visits to hospital were prevented. The public use the A&E department as a primary source for health advice and very few of the calls resulted in admissions. This telephone advice service is effective and helpful to the public but time consuming for A&E nursing staff at peak workload periods in their own department.

Child↗

Use of local neural tube defect registers to interpret national trends.

To conduct a number of studies into the prevalence of neural tube defects (NTD) in the area covered by the Oxford Record Linkage Study (ORLS), multiple sources were used to build a local register of cases occurring in Oxfordshire and West Berkshire between 1968-1990. One source of potential cases--namely, termination and congenital malformation monitoring data available for the locality from the Office of Population Censuses and Surveys (OPCS) data--were kept separate. Comparison of the local cases recorded by OPCS and those known to the register from 1974-1990, using the method of capture-recapture, suggested that national data are only about two thirds complete, but that this underreporting is likely to be reasonably consistent from year to year. OPCS data can therefore be used to study NTD trends if not absolute risks. The local register seemed, by the same yardstick, to be very complete and is being used in a variety of studies of the occurrence of NTD. Survival to one year in this area, over the period 1968-1990, has only improved in the recent past, if at all. Most NTD pregnancies now end in termination rather than birth, and there has been a true decline in the occurrence of NTDs, and likewise the different subtypes.

Abortion, Legal↗