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Biomedical subjects

N Jones

Publications and source records attributed to N Jones.

At least 73 records · Page 4Linked to original sources
PubMed2001

Viral cyclin-cyclin-dependent kinase 6 complexes initiate nuclear DNA replication.

The cyclins encoded by Kaposi sarcoma-associated herpesvirus and herpesvirus saimiri are homologs of human D-type cyclins. However, when complexed to cdk6, they have several activities that distinguish them from D-type cyclin-cdk6 complexes, including resistance to cyclin-dependent kinase inhibitors and an enhanced substrate range. We find that viral cyclins interact with and phosphorylate proteins involved in replication initiation. Using mammalian in vitro replication systems, we show that viral cyclin-cdk6 complexes can directly trigger the initiation of DNA synthesis in isolated late-G(1)-phase nuclei. Viral cyclin-cdk6 complexes share this capacity with cyclin A-cdk2, demonstrating that in addition to functioning as G(1)-phase cyclin-cdk complexes, they function as S-phase cyclin-cdk complexes.

3T3 Cells↗
PubMed2001

Selective expression of electrical correlates of differential appetitive classical conditioning in a feeding network.

Electrical correlates of differential appetitive classical conditioning were recorded in the neural network that underlies feeding in the snail Lymnaea stagnalis. In spaced training (15 trials over 3 days), the lips and the tentacle were used as CS+ (reinforced conditioned stimulus) or CS- (nonreinforced conditioned stimulus) sites for behavioral tactile conditioning. In one group of experimental animals, touch to the lips (the CS+ site) was followed by sucrose (the unconditioned stimulus, US), but touch to the tentacle (the CS- site) was not reinforced. In a second experimental group the CS+/CS- sites were reversed. Semi-intact lip-tentacle-CNS preparations were made from both experimental groups and a naive control group. Intracellular recordings were made from the B3 motor neuron of the feeding network, which allowed the monitoring of activity in the feeding central pattern generator (CPG) interneurons as well as early synaptic inputs evoked by the touch stimulus. Following successful behavioral conditioning, the touch stimulus evoked CPG-driven fictive feeding activity at the CS+ but not the CS- sites in both experimental groups. Naive snails/preparations showed no touch responses. A weak asymmetrical stimulus generalization of conditioned feeding was not retained at the electrophysiological level. An early excitatory postsynaptic potential (EPSP) response to touch was only enhanced following conditioning in the Lip CS+/tentacle CS- group but not in the Tentacle CS+/lip CS- group. The results show that the main features of differential appetitive classical conditioning can be recorded at the electrophysiological level, but some characteristics of the conditioned response are selectively expressed in the reduced preparation.

Animals↗
PubMed2001

Malignant glioma as a secondary malignant neoplasm after radiation therapy for craniopharyngioma: report of a case and review of reported cases.

BACKGROUND: The development of a secondary neoplasm in childhood cancer survivors attains growing importance due to the reported excellent survival and therefore the long exposure to potentially carcinogenic effects of treatment. CASE REPORT: We report a 14-year-old girl in whom a large craniopharyngioma (CP) was diagnosed. After surgery, radiation therapy (RT) was given for residual tumour. Discrete progression necessitated further surgery, resulting in permanent tumour control. Soon after the second surgery hypothalamic-pituitary dysfunction developed together with obesity. Supportive hormone therapy was initiated. Growth hormone (GH) therapy was also given for 15 months. Four years after the diagnosis, a cerebropontine anaplastic astrocytoma WHO grade III was detected, with the main lesion being at the dorsal edge of the irradiated area. The girl died 1 month later from this secondary presumably radiation-induced tumour. Only recently a second child with RT for a CP was diagnosed with malignant glioma in our hospital. CASE REPORTS IN THE LITERATURE: 12 other cases of malignant glioma have been reported after RT for CP. Including our present cases, the mean latency period was 10.7 years (median 9.6 years). However, the shortest latency periods were found in patients who had received GH therapy. In numerous cases, the secondary tumour was seen at the edge of the irradiated volume, and not in the region with the highest absorbed dose. CONCLUSIONS: Therapy-induced secondary gliomas after treatment of CP or other intracranial tumours are rare but dramatic late events with a very poor prognosis. Including our own 2 patients, we reviewed 14 cases of CP with occurrence of a secondary, probably radiation-induced malignant glioma. The short latency periods for patients treated with GH is remarkable. We therefore suspect that GH therapy may accelerate the development of a secondary brain tumour. We are reluctant to recommend GH therapy in conventionally irradiated CP patients. In order to seriously answer the questions about therapy-induced secondary neoplasms, a life-long follow-up is mandatory for all patients who are survivors of childhood cancer.

Adolescent↗
PubMed2001

The benefits of using customized procedure packs.

Discrete item purchasing is the traditional approach for hospitals to obtain consumable supplies for theatre procedures. Although most items are relatively low cost, the management and co-ordination of the supply chain, raising orders, controlling stock, picking and delivering to each operating theatre can be complex and costly. Customized procedure packs provide a solution.

Cost-Benefit Analysis↗
PubMed2001

An infant reciprocal walking orthosis: engineering development.

The growing trend of prescription of reciprocal walking orthoses for children under the age of 5 years has created a requirement for a new design of orthosis in this category. In response to this new demand, a prototype orthosis for infants, incorporating a specially developed hip joint and manufactured as a rehabilitation engineering device within the provisions of the EC Medical Devices Directive, has been produced and tested. A design feature that strongly influences the efficiency of walking is the rigidity of the body brace structure. Monitoring the specific structural performance of the body brace intended for infants showed that it would equal or improve the stiffness achieved in an orthosis for adults. Additionally its strength was comparable with the adult design, which has proven to be safe and reliable in many years of routine prescription. Incorporation of the infant body brace within a complete orthosis provided a structure of more acceptable physical dimensions for these more diminutive patients. The orthosis showed no incipient sign of failure after 100,000 cycles of representative service loading equivalent to that imposed by a 20 kg (5-year-old) patient. The results of structural assessment and cyclic load testing confirm that the design of the orthosis sufficiently satisfies the statutory requirements for devices that are safe and fit for purpose to permit field trials with patients.

Biomechanical Phenomena↗
PubMed2001

Marked tachypnea in siblings with chronic beryllium disease due to copper-beryllium alloy.

Two biological sisters working at the same factory for > 9 years developed chronic beryllium disease (CBD) from a copper-beryllium alloy. Both had marked tachypnea (36 breaths/min and 45 breaths/min at rest, respectively), persisting over 8 years. Ventilation during exercise (assessed in one sibling) was grossly excessive (57 L/min, expected 23 L/min) with a respiratory rate of 64 breaths/min even with normal baseline routine pulmonary function tests. Blood beryllium lymphocyte transformation test and lung biopsies confirmed the diagnosis. No other cases of CBD have been reported from this plant among about 120 workers. These cases support the genetic basis for berylliosis and illustrate the marked tachypnea that may accompany this disease.

Alloys↗
PubMed2001

Achieving reuse of computable guideline systems.

We describe an architecture for reusing computable guidelines and the programs used to interpret them across varied legacy clinical systems. Developed for the PRODIGY 3 project, our architecture aims to support interactive, point of care use of guidelines in primary care. Legacy medical record systems in UK primary care are diverse, using different terminologies, different data models, and varying user-interface philosophies. However, our goal is to provide common guideline knowledge bases and system components, while achieving full integration with the host medical record system, and a user interface tailored to that system. In conjunction with system suppliers, we identified areas of standardization required to achieve this goal. Firstly, standardized interfaces were created for mediation with the legacy system medical record and for act management. Secondly, a standard interface was developed for communication with the User Interface for guideline interaction. Thirdly, a terminology mapping knowledge base and system component was provided. Lastly, we developed a numeric unit conversion knowledge base and system component. The standardization of this architecture was achieved by close collaboration with existing vendors of Primary Care computing systems in the UK. The work has been verified by two suppliers successfully building and deploying systems with User Interfaces which mirror their normal look and feel, communicating fully with existing medical records, while using identical Guideline Interpreter components and knowledge bases. Encouragingly further experiments in other areas of clinical decision support have not required extension of our interfaces.

Artificial Intelligence↗
PubMed2000

Multiple ionization in fast ion-atom collisions: simultaneous measurement of recoil momentum and projectile energy loss

We report on the first experiment that measures simultaneously the full momentum vector of recoil ions and projectile energy loss and scattering angle in ion-atom collisions. We studied multiple ionization in the collisions of 0.83-MeV/u O7+ with Ne. Recoil ions ( Ne(q+), q = 1-8) were detected in coincidence with single capture to O6+. The results give the first experimental evidence for the increase of the average electron energy with increasing recoil charge state q. The average ejection angle shows a dramatic decrease with q. Results are compared with n-electron classical trajectory Monte Carlo calculations.

Journal Article↗
PubMed2000

Crystal structure of a gamma-herpesvirus cyclin-cdk complex.

Several gamma-herpesviruses encode proteins related to the mammalian cyclins, regulatory subunits of cyclin-dependent kinases (cdks) essential for cell cycle progression. We report a 2.5 A crystal structure of a full-length oncogenic viral cyclin from gamma-herpesvirus 68 complexed with cdk2. The viral cyclin binds cdk2 with an orientation different from cyclin A and makes several novel interactions at the interface, yet it activates cdk2 by triggering conformational changes similar to cyclin A. Sequences within the viral cyclin N-terminus lock part of the cdk2 T-loop within the core of the complex. These sequences and others are conserved amongst the viral and cellular D-type cyclins, suggesting that this structure has wider implications for other cyclin-cdk complexes. The observed resistance of this viral cyclin-cdk complex to inhibition by the p27(KIP:) cdk inhibitor is explained by sequence and conformational variation in the cyclin rendering the p27(KIP:)-binding site on the cyclin subunit non-functional.

Amino Acid Sequence↗
PubMed2000

Antimicrobial activity of extracts of eastern North American hardwood trees and relation to traditional medicine.

Wood and bark extracts of 14 eastern North American hardwood tree species which were used traditionally as medicine by First Nation's people were screened for antimicrobial activities with eight strains of bacteria and six strains of fungi. Eighty-six percent of the bark extracts were active against methicillin sensitive Staphylococcus aureus; 71% against Bacillus subtilus and 79% against Mycobacterium phlei. The bark extract of Juglans cinerea was active against Pseudomonas aeruginosa 187, Salmonella typhiumurium, and Klebsiella pneumoniae. The wood extracts were less active: 72% were active against S. aureus (methicillin-sensitive), 36% against B. subtilus and 43% against M. phlei. Results from antifungal tests indicated that 36% of the extracts were active against at least one fungal strain and that bark extracts were more active than wood extracts. The bark extract from Juglans cinerea had the broadest spectrum of activities against Candida albicans, Saccharomyces cerevisiae, Cryptococcus neoformans, Trichophyton mentagrophytes, Microsporum gypseum, and Aspergillus fumigatus. In general, the extracts were more active against gram positive bacteria than gram negative bacteria and against filamentous fungi than yeast-like fungi. The study also demonstrated a correlation between frequency of traditional medicinal use by the First Nations people and antimicrobial activity of extracts indicating that the traditional knowledge encompasses an understanding of aspects of chemical ecology.

Anti-Bacterial Agents↗
PubMed2000

Tek/Tie2 signaling: new and old partners.

A common property amongst angiogenic ligands such as the vascular endothelial growth factors and the angiopoietins is that they can elicit multiple responses depending upon the context of their expression and the presence of other growth factors. Study of the signal transduction pathways initiated by these growth factors provides insight into the molecular and cellular mechanisms that regulate vessel assembly. Key components of signal transduction cascades can then be used as potential targets in angiogenic therapies. This commentary reviews the recent advances into understanding the molecular signaling pathways mediated through the angiopoietin receptor, Tek/Tie2, as well as their effect on the regulation of distinct cellular aspects of angiogenesis.

Animals↗
PubMed2000

The implications of HIV for the anaesthetist and the intensivist.

The acquired immune deficiency syndrome has reached pandemic proportions. Anaesthetists should be aware of the implications of dealing with increasing numbers of both diagnosed and undiagnosed, symptomatic and asymptomatic, human immunodeficiency virus-infected patients in the fields of intensive therapy, operating theatre anaesthesia, obstetrics and pain management. With recent advances, important insights have been gained into the pathogenesis of human immunodeficiency virus. Molecular techniques allow quantification of viral burden, and together with CD4 T-lymphocyte count, prognosis and response to therapy can be evaluated. New drugs and therapeutic regimens have improved prognosis for those who are infected with the virus and vertical transmission of infection from mother to infant can be minimised. Should accidental occupational exposure to the virus occur, a prophylactic regimen of antiretroviral drugs can be administered in an attempt to prevent subsequent human immunodeficiency virus infection.

Analgesia↗
PubMed2000

Percutaneous endoscopic laser discectomy.

BACKGROUND: The aim of the present paper was to systematically review the literature on percutaneous endoscopic laser discectomy (PELD) with respect to the safety and efficacy of the procedure. Where possible the procedure was compared with open discectomy. METHODS: Studies on PELD were identified using MEDLINE (1984 to December 1999), EMBASE (1974 to December 1999) and Current Contents (1993 to Week 1, 2000). A number of search terms were used: PELD; PLDD (percutaneous laser disc decompression); and laser and (spine or lumbar) and (disc* or disk*). The Cochrane Library was searched from 1966 to issue 4, 1999, using the search terms 'discectomy' or 'discotomy'. Live human studies of patients with lumbar disc prolapses for whom surgery was appropriate were included. Cadaver studies were also included. A surgeon and reviewer independently assessed the retrieved articles for their inclusion in the review. RESULTS: Only 12 papers were identified that related to PELD. The level of evidence for safety and efficacy was low; there were no controlled, blinded or randomized studies. The highest level of evidence came from time series studies. No quantitative analysis could be undertaken for the present review. CONCLUSIONS: Given the extremely low level of evidence available for this procedure it was recommended that the procedure be regarded as experimental until results are available from a controlled clinical trial, ideally with random allocation to an intervention and control group.

Cadaver↗
PubMed2000

Nocardial infection as a complication of HIV in South Africa.

OBJECTIVES: To assess the occurrence, clinical and microbiological features of nocardial infections complicating HIV in Soweto, South Africa. METHODS: A prospective study was carried out over a 2-year period. Patients were identified after isolation of Nocardia spp. from a clinical specimen. Clinical details were recorded. The nocardial isolates were identified to species level and susceptibility tests performed. RESULTS: Ten patients were identified as having nocardial disease complicating HIV. Clinical presentations were pulmonary (five patients), pulmonary and cerebral (one patient), cerebral (one patient) and skin and soft tissue infection of the lower limb (three patients). Three infections were fatal. The isolates were Nocardia asteroides (seven patients), N. farcinica (two patients) and Nocardia spp. (one). Isolates of N. farcinica demonstrated opacification of Middlebrook agar. All isolates were sensitive to amikacin and minocycline. Most nocardial isolates were susceptible to cefotaxime, imipenem and coamoxiclav. In vitro resistance to cotrimoxazole was present in five. CONCLUSIONS: Nocardial infection occurs as a complication of HIV infection in the Republic of South Africa. Pulmonary cases may be difficult to distinguish from tuberculosis. Nocardia asteroides is the most common species isolated. Nocardia farcinica has resistance to multiple antibacterial agents and demonstrates opacification of Middlebrook agar, a useful screening test for this species. Agents with good in vitro antinocardial activity were amikacin, minocycline, cefotaxime, imipenem and coamoxiclav. There was a high level of resistance in vitro to cotrimoxazole.

AIDS-Related Opportunistic Infections↗
PubMed2000

Upregulation of amyloid precursor protein and its mRNA in an experimental model of paediatric head injury.

Amyloid precursor protein (APP), a membrane spanning glycoprotein which plays an important role in neuronal growth and synaptic plasticity, is increased after traumatic brain injury (TBI) and has been used as a sensitive marker of neuronal damage in an adult sheep head impact model. We hypothesised that APP expression would similarly be increased in lambs, suggesting that in the immature injured brain APP is also upregulated as an acute phase response to trauma. Ten anaesthetised and ventilated 4-5 week old Merino lambs sustained a left temporal head impact from a humane stunner. At 2 h after impact, there was widespread and intense neuronal cell body APP immunoreactivity which was more widely distributed than axonal APP. APP messenger RNA (mRNA) expression was also markedly increased with a distribution similar to that of APP antigen. These results demonstrate that APP antigen and mRNA are sensitive early indicators of TBI in paediatric cases.

Amyloid beta-Protein Precursor↗