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Biomedical subjects

P S Jones

Publications and source records attributed to P S Jones.

At least 19 recordsLinked to original sources
PubMed2006

How affected is oxygen metabolism in DWI lesions?: A combined acute stroke PET-MR study.

OBJECTIVE: To use back-to-back diffusion-weighted imaging (DWI) and PET to obtain quantitative measures of the cerebral metabolic rate of oxygen (CMRO(2)) within DWI lesions, and to assess the perfusion-metabolism coupling status by measuring the cerebral blood flow and the oxygen extraction fraction within DWI lesions. METHODS: Six prospectively recruited acute carotid-territory stroke patients completed the imaging protocol, which was commenced 7 to 21 hours from onset and combined DWI derived from state-of-the-art diffusion tensor imaging sequencing using a 3-T magnet and fully quantitative (15)O-PET. The PET variables were obtained in individual DWI lesions in each patient. RESULTS: Across patients, the CMRO(2) was reduced in the DWI lesion relative to mirror (mean reduction 39.5%; p = 0.028). Examining individual DWI lesions, however, revealed considerable variability in the extent of this CMRO(2) reduction. The flow-metabolism coupling pattern underlying the DWI lesion was also variable, including ongoing ischemia, mild oligemia, and partial or complete reperfusion. DISCUSSION: Diffusion-weighted imaging (DWI) lesions generally reflect substantial disruption of energy metabolism. However, the degree of metabolic disruption is variable, indicating DWI lesions may not always represent irreversibly damaged tissue. Finally, because DWI lesions can persist despite reperfusion, assessment of perfusion is necessary for interpretation of DWI changes in acute stroke.

Aged↗
PubMed2006

Does healthy aging affect the hemispheric activation balance during paced index-to-thumb opposition task? An fMRI study.

Normal aging is generally associated with declining performance in cognitive and fine motor tasks. Previous functional imaging studies have been inconsistent regarding the effect of aging on primary motor cortex (M1) activation during finger movement, showing increased, unchanged or decreased activation contralaterally, and more consistently increased activation ipsilaterally. Furthermore, no study has addressed the effect of age on M1 hemispheric activation balance. We studied 18 optimally healthy right-handed subjects, age range 18-79 years (mean +/- SD: 47 +/- 17) using 3 T fMRI and right index finger-thumb tapping auditory-paced at 1.25 Hz. The weighted Laterality Index (wLI) for M1 was obtained according to Fernandez et al. (2001) [Fernandez, G., de Greiff, A., von Oertzen, J., Reuber, M., Lun, S., Klaver, P., et al. 2001. Language mapping in less than 15 min: real-time functional MRI during routine clinical investigation. Neuroimage 14 585-594], with some modifications. The wLI, as well as the total activation on each side, were assessed against age using non-parametric correlation. There was a highly significant negative correlation between age and wLI such that the older the subjects, the lower the wLI. Furthermore, there was a highly significant positive correlation between total activation for ipsilateral M1 and age, and a nearly significant trend for contralateral M1. This study documents that during execution of a simple paced motor task, the older the subject the less lateralized the M1 activation balance as a result of increasing amount of activation on both sides, more significantly so ipsilaterally. Thus, in aging, enhanced M1 recruitment bilaterally is required to produce the same motor performance, suggesting a compensatory process. These findings are in line with cognitive studies indicating a tendency for the aging brain to reduce its functional lateralization, perhaps from less efficient transcallosal connections.

Acoustic Stimulation↗
PubMed2005

Quantification of index tapping regularity after stroke with tri-axial accelerometry.

OBJECTIVE: Quantifying intrinsic components of movement may help to better understand the nature of motor deficits after stroke. Here we quantify the ability of stroke patients to finger tap in rhythm with auditory cues given at physiological rate. METHODS: Using tri-axial accelerometry, we measured tapping regularity (Regularity Index) during auditory-cued index-to-thumb tapping at 1.25 Hz in 20 prospectively selected right-handed chronic stroke patients (mean age 61 yrs) and 20 right-handed healthy subjects (7 young and 13 age matched; mean age 24 and 58 yrs, respectively). With the aim to validate our method, two measures of clinical deficit, the European Stroke Scale (ESS) and the maximum number of index-thumb taps in 15s (IT-Max) were recorded on the same day. RESULTS: There was no effect of age or hand used on the Regularity Index in the control subjects. In patients, the Regularity Index of their affected hand was significantly worse compared to their unaffected hand and to age-matched controls (p<0.05 and p<0.01, respectively). The Regularity Index significantly correlated with the ESS and IT-Max in the clinically expected direction (p=0.025 and 0.001, respectively). CONCLUSION: These data indicate that our method has validity to quantify finger-tapping regularity. After stroke, there is a deficit in the ability to keep pace with auditory cues that correlates, but does not equate, with other indices of motor function. Quantifying tapping regularity may provide novel insights into the mechanisms underlying recovery of finger dexterity after stroke.

Acoustic Stimulation↗
PubMed2004

Clearing the cervical spine in unconscious adult trauma patients: a survey of practice in specialist centres in the UK.

A postal questionnaire survey of neurosurgery and spinal injury departments in the UK was conducted to determine how they assessed the cervical spine in unconscious, adult trauma patients, and at what point immobilisation was discontinued. Of the 32 units contacted, 27 responded (response rate, 84%). Most centres had no protocols to guide initial imaging or when immobilisation devices should be removed. Most responding centres performed fewer than three plain radiographs, and most did not use computerised tomography routinely. Routine use of magnetic resonance imaging or dynamic flexion-extension fluoroscopy was rare, and few units regarded the latter as safe in unconscious patients. There was no consensus on when immobilisation of the cervical spine should be discontinued. Most centres that terminated immobilisation immediately after imaging did so on the basis of plain radiographs alone. Unconscious adult trauma patients remain at risk of inadequate assessment of potential cervical spine injuries.

Adult↗
PubMed2001

Quantitative measurements of edge-to-face aromatic interactions by using chemical double-mutant cycles.

Synthetic H-bonded zipper complexes have been used to quantify the magnitude of an edge-to-face aromatic interaction between a benzoyl group and an aniline ring. Four chemical double-mutant cycles were constructed by using a matrix of nine closely related complexes in which the aromatic rings were sequentially substituted for alkyl substituents. The stability constants and three-dimensional structures of the complexes were determined by using 1H NMR titrations in deuterochloroform at room temperature. The value of the interaction energy is similar in all cases, the average is -1.4 +/- 0.5 kJ mol(-1). The scope and limitations of the double-mutant approach are explored, and the consequences of conformational equilibria are discussed.

Journal Article↗
PubMed2001

Role integration and perceived health in Asian American women caregivers.

In this study, role involvement, role integration (including role stress and role satisfaction), and perceived health were examined in 50 Asian American women who were caregivers of aging parents in addition to being wives, mothers, and employees. Their mean age was 47.8 years. Twenty-nine of the participants were Chinese and 21 Filipino, with an average length of caregiving for each group of 11 years. All participants were born outside the United States. Instruments used in the study were translated and back-translated into Chinese and Tagalog and tested for validity and reliability. The association of role involvement, role integration, role stress, and role satisfaction with perceived physical and psychological health in the combined and separate groups was examined. Role involvement was not associated with health in the combined group of caregivers but was associated with overall health in the sample of Chinese women. Role integration was positively associated with all three perceived health measures in the Filipino group but not in the Chinese group. Role satisfaction was consistently high in both groups. Role satisfaction and psychological well-being were significantly correlated for the combined group and for the Filipino caregivers. Total role stress was significantly correlated with overall health and current health only in the combined group. Thus, support that helps to decrease role stress and to increase role satisfaction may be more effective than efforts to decrease the extent of role involvement.

Acculturation↗
PubMed2001

Alterations in chromatin structure are implicated in the activation of the steroid hormone response unit of the ovalbumin gene.

Hormone-responsive genes rely on complex regulatory elements known as hormone response units to integrate various regulatory signals. Characterization of the steroid-dependent regulatory element (SDRE) in the check ovalbumin gene (--892 to --796) suggests that it functions as a hormone response unit. Previous studies using gel mobility shift assays and several types of footprinting analyses demonstrated that proteins bind to this entire element in vitro even in the absence of steroid hormones. However, the genomic footprinting experiments described herein indicate that the binding of three different proteins or protein complexes to the SDRE requires estrogen and corticosterone, suggesting that the chromatin structure of this site is restricted in vivo. Transfection experiments using linker scanning and point mutations support the contention that the binding of these three complexes is essential for induction of the ovalbumin gene by steroid hormones. In addition, functional analyses suggest that a fourth complex is also necessary for maximal induction. These and other data suggest that the SDRE functions as a hormone response unit to coordinate signals generated by two steroid hormones.

Animals↗
PubMed2001

Comparisons of the effects of tamoxifen, toremifene and raloxifene on enzyme induction and gene expression in the ovariectomised rat uterus.

This study compares the actions of oestradiol, tamoxifen, toremifene and raloxifene on enzyme and gene expression in uterine tissues of ovariectomised rats over 72 h. The time-course for the induction of ornithine decarboxylase by the compounds showed a rapid biphasic response, while for creatine kinase brain type (BB) there was a continued increase over 72 h. The efficacy of induction showed that, with both markers, oestradiol gave the highest induction level, followed by tamoxifen or toremifene and then raloxifene. RT-PCR demonstrated that all compounds decreased oestrogen receptor (ER) alpha, ERbeta and ERbeta2 gene expression, 8-24 h after the first dose, suggesting that down-regulation of ER is not the primary cause of the difference in efficacy between these compounds. Using cDNA arrays, expression of 512 genes was examined in the uteri of oestradiol- or tamoxifen-treated rats. Both compounds resulted in the up-regulation of heat-shock protein 27, telomerase-associated protein 1 and secretin. However, most surprising was the marked down-regulation of Wilms' tumour and retinoblastoma genes. We speculate that this may result in a loss of regulation of the transition from the G1 to the S phase in the cell cycle and may make cells more vulnerable to the carcinogenic effects of tamoxifen in this tissue.

Animals↗
PubMed2000

Empowerment of nursing as a socially significant profession in Vietnam.

PURPOSE: To describe nursing education and practice in Vietnam, and strategies that support empowerment of nursing as a socially significant profession for that country. DESIGN: The Jones-Meleis health empowerment model was used as a framework to examine barriers and identify strategies that support empowerment. METHODS: Fieldwork, interviews, and participation-observation in collaborative partnerships with the Ministry of Health, the national nurses association, and schools of nursing in Vietnam. FINDINGS: Nurses in Vietnam are eagerly poised to make significant and essential contributions to the well-being of society. CONCLUSIONS: Baccalaureate and master's degree nursing curricula taught by nurses are necessary for professionalization of nursing practice in Vietnam.

Humans↗
PubMed2000

Novel approaches to the treatment of hepatitis C virus infection.

Hepatitis C virus (HCV) has infected millions of people worldwide and emerged as a global health crisis. This review reports approaches currently being taken to combat the virus. Viral targets have received the most attention, particularly the NS3 serine protease where potent inhibitors have been described. Crystal structures of key replicative enzymes, NS3 protease, NS3 helicase, NS5B polymerase and now full-length NS3 protease-helicase, are available. More recently, targeting the host system has become of interest, particularly inhibitors of inosine monophosphate dehydrogenase. Research aimed at novel treatments for HCV disease is gathering pace and very recent developments in cell-based assay systems can only hasten the discovery of improved therapies.

Amino Acid Sequence↗
PubMed1999

Activation of transcription by estrogen receptor alpha and beta is cell type- and promoter-dependent.

Tamoxifen acts as a strong estrogen antagonist in human breast but as an estrogen agonist in the uterus. The action of tamoxifen is mediated through estrogen receptors (ERalpha and ERbeta), which bind to a variety of responsive elements, to activate transcription. To examine the role of these varied elements in the response to antiestrogens, we studied the activation of a panel of differing promoters, by these compounds, in human breast, bone, and endometrial derived cell lines. No agonistic activity was observed in breast cells, whereas all antiestrogens, particularly tamoxifen, exhibited agonistic effects in uterine cell lines. All antiestrogens studied were agonistic in co-transfections of a collagenase reporter gene and ERbeta, but tamoxifen alone was agonistic with ERalpha in (uterine) HEC-1-A cells. The ERalpha mediated, agonism of tamoxifen was not observed in primary cultures of human uterine stromal cells, whereas the ERbeta-mediated agonism of all selective estrogen receptor modulators was present. This suggests that the two receptors operate by distinct pathways and that the response of cells to antiestrogens is dependent on the ER subtypes expressed.

Blotting, Western↗
PubMed1999

The design and synthesis of potent inhibitors of hepatitis C virus NS3-4A proteinase.

Hepatitis C virus (HCV) is the cause of the majority of transfusion-associated hepatitis and a significant proportion of community-acquired hepatitis worldwide. Infection by HCV frequently leads to persistent infections that result in a range of clinical conditions including an asymptomatic carrier state, severe chronic active hepatitis, cirrhosis and, in some cases, hepatocellular carcinoma. The HCV genome consists of a single-stranded, positive sense RNA containing an open reading frame of approximately 9060 nucleotides. This is translated into a single polyprotein of approximately 3020 amino acids (C-E1-E2-p7-NS2-NS3-NS4A-NS4B-NS5A-NS5B), which in turn is processed by a series of host and viral proteinases into at least 10 cleavage products. The N-terminal portion of the NS3 protein encodes a serine proteinase that is responsible for the cleavage at the NS3-4A, NS4A-4B, NS4B-5A and NS5A-5B junctions. The 54 amino acid NS4A protein is a cofactor that binds to the NS3 protein and enhances its proteolytic activity. This report describes the expression of a recombinant NS3-4A proteinase fusion protein in Escherichia coli and the in vitro characterization of the enzyme activity using synthetic peptide substrates. It then demonstrates how these results were employed to guide the design of potent inhibitors of this enzyme.

Amino Acid Sequence↗
PubMed1998

Assessment of neuroendocrine dysfunction following traumatic brain injury.

Posttraumatic neuroendocrine pathology may be a clinically significant complication following traumatic brain injury (TBI). Metabolic abnormalities are described after TBI in two cases. A 21 year old male injured in a motor vehicle accident admitted in a minimally responsive condition presented with fluctuating high sodium levels, undetectable serum testosterone, and depressed cortisol and thyroid function. Imaging revealed near complete avulsion of the pituitary stalk leading to panhypopituitarism. A 38 year old male admitted for occipital skull fractures and brain contusions presented with hyponatremia and low serum testosterone. Both patients required hormonal replacement and correction of electrolyte abnormalities. A screening protocol adapted for selected patients at risk for endocrine problems is described. While neuroendocrine screening is not advocated in all TBI patients, physicians should be aware of the importance of neuroendocrine dysfunction following TBI.

Adult↗
PubMed1998

Strategies for antiviral drug discovery.

The need for antiviral drugs is growing rapidly as more viral diseases are recognized. The methods used to discover antiviral drugs have evolved considerably over the past 40 years and the overall process of discovery can be broken down into subprocesses which include lead generation, lead optimization and lead development. Various methods are now employed to ensure these processes are carried out efficiently. For lead generation, screening methodologies have developed to the extent where hundreds of thousands of compounds can be screened against a particular target. An alternative approach is to use the structures of enzyme substrates as a starting point for drug discovery. Much use is now made of X-ray crystallographic data of target-inhibitor complexes for the optimization of lead structures, and methods for preparing libraries of compounds to assist both generation and optimization of leads are well-developed. The methods used to predict and improve the pharmacokinetic properties of compounds are also changing rapidly. Finally, novel approaches to antiviral therapy using oligonucleotide-based compounds or by modulating the host immune response are also being explored. This review discusses these approaches, provides examples of where their application has been successful and sets them against a historical background.

Anti-HIV Agents↗