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Biomedical subjects

J Richardson

Publications and source records attributed to J Richardson.

At least 19 recordsLinked to original sources
PubMed1997

Molecular characterization of two mammalian bHLH-PAS domain proteins selectively expressed in the central nervous system.

Here we describe two mammalian transcription factors selectively expressed in the central nervous system. Both proteins, neuronal PAS domain protein (NPAS) 1 and NPAS2, are members of the basic helix-loop-helix-PAS family of transcription factors. cDNAs encoding mouse and human forms of NPAS1 and NPAS2 have been isolated and sequenced. RNA blotting assays demonstrated the selective presence of NPAS1 and NPAS2 mRNAs in brain and spinal cord tissues of adult mice. NPAS1 mRNA was first detected at embryonic day 15 of mouse development, shortly after early organogenesis of the brain. NPAS2 mRNA was first detected during early postnatal development of the mouse brain. In situ hybridization assays using brain tissue of postnatal mice revealed an exclusively neuronal pattern of expression for NPAS1 and NPAS2 mRNAs. The human NPAS1 gene was mapped to chromosome 19q13.2-q13.3, and the mouse Npas1 gene to chromosome 7 at 2 centimorgans. Similarly, the human NPAS2 gene was assigned to chromosome 2p11.2-2q13, and the mouse Npas2 gene to chromosome 1 at 21-22 centimorgans. The chromosomal regions to which human NPAS1 and NPAS2 map are syntenic with those containing the mouse Npas1 and Npas2 genes, indicating that the mouse and human genes are true homologs.

Amino Acid Sequence↗
PubMed1996

The reliability and validity of work measurement in Australian general practice consultations.

OBJECTIVES: To examine the reliability of relative work value assessment in general practice consultations and to determine whether different methods of assessing work produce consistent rankings. DESIGN: Cross-sectional observational assessment of general practice consulations. SETTING: General practices in Victoria between October 1991 and October 1992. PARTICIPANTS: 686 patients attending one of 58 general practitioners (GPs) drawn from a random, stratified sample. METHODS: Each participating GP had one day of consultations videotaped. They rated the work value of each consultation by using a magnitude estimation scale relative to a reference vignette. Three GP observers independently applied the same scale to the videotaped consultations. After three months, the observers applied a second measurement of work value, a compensation scale (also relative to the reference vignette), to the videotaped consultations. Duration of consultation was the third rating method. MAIN OUTCOME MEASURES: The reliability of work value assessment for each scale. Consultation rank order correlation coefficients among all rating methods. RESULTS: Observer reliability was high for both scales. Practising GPs showed lower levels of reliability in assessing the work value of their consultations. Strong positive correlations were found for consultation rankings among the observer scales and duration of the consultation. The duration of the consultation emerged as an important predictor of consultation work value. CONCLUSIONS: Scaling methods appear to be of little value to the practising GP in reliably assessing the relative work value of their consultations; training in the use of these scales may improve their reliability. However, the duration of consultation may be a reasonable proxy for relative work value assessment in general practice consultations.

Australia↗
PubMed1996

Workplace organizational correlates of lost-time accident rates in manufacturing.

We report the results of a questionnaire survey of manufacturing workplaces related to the lost-time frequency rates (LTFR) for Workers' Compensation claims. Six types of industry were chosen.' metal articles, plastic articles, grain products, textile manufacturing, printing, and automobile manufacturing. LTFR were standardized by type of industry. Stratifying simultaneously by number of employees and LTFR category, we sampled 718 workplaces. A mail questionnaire to labor and management representatives provided at least some information on 58%. Response rates were similar across LTFR categories, and telephone interviews of non-responders showed little difference in their replies from those obtained in completed questionnaires. A large number of variables were examined. Apart from statistical significance, we looked for consistency in trends across LTFR categories and in patterns for similar questions. Significant associations grouped into several areas. Lower LTFR were associated with: concrete demonstration by management of its concern for the workforce; greater involvement of workers in general decision-making; greater willingness of the Joint Health and Safety Committee to solve problems internally; and greater experience of the workforce. Variables that were not significant included profitability and financial performance. A final stepwise multiple regression explained 19% of the variance in LTFR, although this analysis suffered from several limitations.

Absenteeism↗
PubMed1996

Resonance assignments for Oncostatin M, a 24-kDa alpha-helical protein.

Oncostatin M (OM) is a cytokine that shares a structural and functional relationship with interleukin-6, leukemia inhibitory factor, and granulocyte-colony stimulating factor, which regulate the proliferation and differentiation of a variety of cell types. A mutant version of human OM in which two N-linked glycosylation sites and an unpaired cysteine have been mutated to alanine (N76A/C81A/N193A) has been expressed and shown to be active. The triple mutant has been doubly isotope-labeled with 13C and 15N in order to utilize heteronuclear multidimensional NMR techniques for structure determination. Approximately 90% of the backbone resonances were assigned from a combination of triple-resonance data (HNCA, HNCO, CBCACONH, HBHACONH, HNHA and HCACO), intraresidue and sequential NOEs (3D 15N-NOESY-HMQC and 13C-HSQC-NOESY) and side-chain information obtained from the CCONH and HCCONH experiments. Preliminary analysis of the NOE pattern in the 15N-NOESY-HMQC spectrum and the 13C alpha secondary chemical shifts predicts a secondary structure for OM consisting of four alpha-helices with three intervening helical regions, consistent with the four-helix-bundle motif found for this cytokine family. As a 203-residue protein with a molecular weight of 24 kDa, Oncostatin M is the largest alpha-helical protein yet assigned.

Amino Acid Sequence↗
PubMed1996

Synthetic peptides entrapped in microparticles can elicit cytotoxic T cell activity.

Peptides from Plasmodium berghei circumsporozoite protein (CS) and influenza A virus nucleoprotein (NP) were entrapped in microparticles prepared from poly (lactide-co-glycolide) polymers, and the microparticles were administered parenterally to mice. After immunization with single or multiple doses, splenocytes were tested for a cytotoxic T cell (CTL) response and high levels of CTL activity were detected. The CTL induced were CD8+, MHC class I restricted, and could recognize virus infected cells. Peptide entrapped in microparticles of mean size < 500 nm were better inducers of CTL than larger microparticles (mean > 2 microns and above). Microparticles could also be used to deliver lipid modified peptides (lipopeptides) and elicited higher levels of cytolytic activity than either free peptide in microparticles or lipopeptide alone. Microparticles provide a novel way of inducing a CTL response using synthetic peptides.

Adjuvants, Immunologic↗
PubMed1996

The measurement of utility in multiphase health states.

To examine the validity of the additive quality-adjusted life year model used to evaluate a multiphase health state, data from a pilot study of mammography were used to determine whether the values assigned to a multiphase postmastectomy health state could be estimated from a combination of the independently rated constituent health state values. The results suggest that they cannot.

Adult↗
PubMed1996

Spatial patterns in the control of human arm movement.

Generalized Procrustes analysis was used to investigate the spatial paths of pointing movements. In Experiment 1, 3 participants produced similar spatial paths of the hand when repeating a pointing movement many times, despite variability in the position and orientation of the movements. The average spatial path indicates a fundamental spatial pattern of the motor system, or motor primitive. This pattern varied across the workspace. Anterioposterior movements were straight, but repeated movements had variable spatial patterns. Lateral movements were curved away from the body but had regular spatial patterns. Experiment 2 extended these results to movements of different amplitudes in 7 participants. The motor primitive seems to be abandoned at the end of the movement in favor of final adjustments to bring the hand to the target position. In Experiment 3, the same participants produced similar motor primitives both with and without vision.

Arm↗
PubMed1996

Neutralization sensitivity and accessibility of continuous B cell epitopes of the feline immunodeficiency virus envelope.

Antibodies elicited during natural infection of domestic cats by the feline immunodeficiency virus (FIV) recognize continuous epitopes in nine domains of the virus envelope glycoproteins. Whereas antibodies directed against the V3 envelope region can neutralize laboratory-adapted virus, neutralization of FIV has been shown to depend upon cellular substrate, and virus adaptation to laboratory cell lines may alter sensitivity to neutralizing antibodies. We therefore undertook a systematic analysis of the continuous B cell epitopes of the envelope of a primary FIV isolate, Wo. The capacity of feline antisera elicited against nine envelope domains to neutralize primary and laboratory-adapted virus was evaluated in feline peripheral blood mononuclear cells (PBMC). The laboratory-adapted strain Petaluma was used to compare neutralization in PBMC and Crandell feline kidney cells (CrFK). Antibodies specific for the V3 region neutralized both primary and laboratory-adapted virus whether residual infectivity was measured in CrFK or in feline PBMC. However, a large discrepancy in the efficiency of neutralization was observed in these ex vivo models of infection, perhaps reflecting diversity in the interaction between virus and different cellular targets. We also examined the accessibility of epitopes on the functional oligomeric envelope complex of FIV. Most of the epitopes were poorly exposed on native envelope glycoproteins at the surface of live infected cells. The most accessible domain was the only domain sensitive to neutralizing antibodies. These results suggest that inaccessibility on oligomeric envelope glycoproteins may frequently underlie the insensitivity of diverse lentivirus B cell epitopes to neutralization.

Amino Acid Sequence↗
PubMed1996

Thoracic paravertebral space location. A new method using pressure measurement.

The major drawback of paravertebral space location using the traditional method of loss of resistance to air or saline is a failure rate of at least 10%. We investigated whether pressure measurement during needle advancement could improve reliability. Twenty-nine blocks in 14 awake adult patients undergoing treatment for chronically painful neuralgic conditions of the chest or abdominal wall were studied. In erector spinae, the mean inspiratory pressure (29.5 mmHg, SD 14.2), exceeded the expiratory pressure (19.4 mmHg, SD 9.7). However, upon traversing the superior costo-transverse ligament, there was a sudden lowering of pressures and the mean expiratory pressure (7.6 mmHg, SD 3.7) exceeded the inspiratory pressure (3.3 mmHg, SD 2.9). No negative pressures were recorded. Correct needle placement was confirmed by X ray screening and contrast injection. All blocks were successful and uncomplicated. Location of the paravertebral space by this objective method of 'pressure inversion' improves sensitivity and specificity and should lead to an improvement in the success rate of thoracic paravertebral analgesia.

Adult↗
PubMed1996

Knockout of the two ldh genes has a major impact on peptidoglycan precursor synthesis in Lactobacillus plantarum.

Most bacteria synthesize muramyl-pentapeptide peptidoglycan precursors ending with a D-alanyl residue (e.g., UDP-N-acetylmuramyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala). However, it was recently demonstrated that other types of precursors, notably D-lactate-ending molecules, could be synthesized by several lactic acid bacteria. This particular feature leads to vancomycin resistance. Vancomycin is a glycopeptide antibiotic that blocks cell wall synthesis by the formation of a complex with the extremity of peptidoglycan precursors. Substitution of the terminal D-alanine by D-lactate reduces the affinity of the antibiotic for its target. Lactobacillus plantarum is a lactic acid bacterium naturally resistant to vancomycin. It converts most of the glycolytic pyruvate to L- and D-lactate by using stereospecific enzymes designated L- and D-lactate dehydrogenases, respectively. In the present study, we show that L. plantarum actually synthesizes D-lactate-ending peptidoglycan precursors. We also report the construction of a strain which is deficient for both D- and L-lactate dehydrogenase activities and which produces only trace amounts of D- and L-lactate. As a consequence, the peptidoglycan synthesis pathway is drastically affected. The wild-type precursor is still present, but a new type of D-alanine-ending precursor is also synthesized in large quantities, which results in a highly enhanced sensitivity to vancomycin.

Anti-Bacterial Agents↗
PubMed1996

Double jeopardy, the equal value of lives and the veil of ignorance: a rejoinder to Harris.

Harris levels two main criticisms against our original defence of QALYs (Quality Adjusted Life Years). First, he rejects the assumption implicit in the QALY approach that not all lives are of equal value. Second, he rejects our appeal to Rawls's veil of ignorance test in support of the QALY method. In the present article we defend QALYs against Harris's criticisms. We argue that some of the conclusions Harris draws from our view that resources should be allocated on the basis of potential improvements in quality of life and quantity of life are erroneous, and that others lack the moral implications Harris claims for them. On the other hand, we defend our claim that a rational egoist, behind a veil of ignorance, could consistently choose to allocate life-saving resources in accordance with the QALY method, despite Harris's claim that a rational egoist would allocate randomly if there is no better than a 50% chance of being the recipient.

Australia↗
PubMed1996

Another peep behind the veil.

Harris argues that if QALYs are used only 50% of the population will be eligible for survival, whereas if random methods of allocation are used 100% will be eligible. We argue that this involves an equivocation in the use of "eligible", and provides no support for the random method. There is no advantage in having a 100% chance of being "eligible" for survival behind a veil of ignorance if you still only have a 50% chance of survival once the veil is lifted. A 100% chance of a 50% chance is still only a 50% chance. We also argue that Harris provides no plausible way of dealing with the criticism that his random method of allocation may result in the squandering of resources.

Australia↗
PubMed1996

Varicella-zoster virus DNA in CSF and arteries in delayed contralateral hemiplegia: evidence for viral invasion of cerebral arteries.

A 78-year-old woman presented with a right basal ganglia infarct 6 weeks after a left herpes zoster ophthalmicus. MR angiography showed focal segmental stenosis of the proximal segments of the anterior, middle, and posterior cerebral arteries. Varicella DNA was detected in the CSF by polymerase chain reaction (PCR). Treated with dexamethasone and acyclovir without improvement, she died 1 month later. There was focal endarteritis in the left anterior, middle, and posterior cerebral arteries at autopsy. Varicella DNA was detected by PCR of extracts from these vessels but not from the arteries on the right side. This study provides further evidence that the vasculopathy after herpes zoster ophthalmicus results from direct viral invasion of the vessel wall.

Aged↗
PubMed1996

Results of surgical treatment of stage I and II lung cancer.

Pulmonary resection remains the most appropriate treatment for localised bronchogenic carcinoma, since prognosis and outcome are currently dependent on surgical resectability. A retrospective analysis of our experience with three hundred and thirteen stage I (n=250) and stage II (n=63) patients treated surgically form the basis of this report. The initial pulmonary resection was lobectomy in 173 patients, bilobectomy in 38, sleeve lobectomy in 12, pneumonectomy in 59, wedge excision or segmentectomy in 31. The overall operative mortality was 3.2%; 4.03% for lobectomy and 1.6% for pneumonectomy. Morbidity was observed in 21 (6.7%) patients. Four out of sixteen small cell carcinoma patients had postoperative adjuvant chemotherapy. Survival in patients with stage I tumours was 71% at 5 years and 61% at 10 years compared with 41% at 5 years and 35% at 10 years for patients with stage II disease. The five year survival after pneumonectomy was significantly (p<0.05) better for both stage I and stage II lung cancer than after lobectomy. Five year survival in stage I carcinoma was not influenced by histological type, while there was statistically significant difference (p<0.05) in survival between adenocarcinoma (0%) and squamous cell carcinoma (46%) in stage II disease. We conclude that an aggressive surgical approach can provide an excellent prognosis for recovery and long term cure in most patients with early stage lung cancer.

Carcinoma, Bronchogenic↗
PubMed1996

Domestic violence: a hidden problem for general practice.

Domestic violence is a common problem that may affect more than a quarter of women. It is a complex area in which to undertake research. Studies often focus on selected populations and exhibit a diversity of design, making comparison difficult. This review focuses on physical violence by men against women partners or ex-partners, and exemplifies important issues for general practitioners. Domestic violence frequently goes undetected. This may be the result of doctor's fears of exploring an area perceived as time-consuming, where knowledge is lacking and where they feel powerless to 'fix' the situation. Women may not reveal that they are experiencing violence, sometimes because doctors are unsympathetic or hostile. Nevertheless, women wish to be asked routinely about physical abuse and want to receive immediate advice and information about their options if necessary. Women experience a range of health and social problems in association with domestic violence, including depression, anxiety, substance abuse and pregnancy complications. However, none of these features is specific enough to be useful as an indicator of violence. Therefore, doctors should routinely ask all women direct questions about abuse. This recommendation can be incorporated into guidelines, which should be implemented widely in the UK, to improve the care of women experiencing domestic violence. In parallel with this, the educational needs of general practitioners should be addressed. Further research is needed to establish the prevalence of domestic violence in women presenting to general practice and to investigate how the problem is currently being addressed. If progress is to be made in tackling domestic violence, action within primary care is just one part of this: a fundamental change in the attitudes of men towards women is required.

Family Practice↗