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Biomedical subjects

C James

Publications and source records attributed to C James.

At least 73 records · Page 4Linked to original sources
PubMed1998

Fermenting debate: do yeast undergo apoptosis?

Apoptosis is a common feature of multicellular organisms. However, the recent observations of non-metazoan cell deaths displaying morphology reminiscent of apoptosis has suggested the existence of an ancestral cell death machinery. We discuss this possibility and its implications for the use of yeast in the dissection of the metazoan apoptotic process.

Animals↗
PubMed1998

Enhanced detection of malignant lymphoma in cerebrospinal fluid by multiparameter flow cytometry.

Immunophenotyping by flow cytometry has not been widely applied to cerebrospinal fluid (CSF) analysis. We attempted to optimize flow cytometric detection of malignant lymphoma in CSF samples by the routine use of 3- and 4-color flow cytometry, with specific selection of lymphoid cells by fluorescence vs 90 degrees light scatter gating. Thirty-six consecutive CSF samples were immunophenotyped by flow cytometry, and the results were compared with those of standard microscopic examination. Lymphoid events were adequate for analysis in 27 of the 36 samples. Each of the 9 unsuccessful samples was more than 24 hours old at analysis or contained fewer than 1 x 10(4) total cells (< or =1 cell/microL). Lymphoma was detected in 10 of the remaining 27 cases. Six lymphomas were detected by morphology and flow cytometry, 1 only by morphologic examination, and 3 only by flow cytometry. Therefore, the combination of flow cytometry and morphologic examination enhanced the detection by 43% over morphologic examination alone. Flow cytometry permitted the detection of lymphoid clones totaling less than 1% of total cells. Multicolor flow cytometry is a rapid and sensitive technique that enhances detection of lymphoma in paucicellular CSF samples. Given the great sensitivity of flow cytometry, future studies will be necessary to assess the significance of detecting small lymphoid clones in this setting.

Antigens, CD↗
PubMed1998

Cellular pathways of mast cell- and capsaicin-sensitive nerve-evoked ileal submucosal arteriolar dilations.

This study characterized mast cell- and capsaicin-sensitive sensory nerve vasodilator mechanisms regulating submucosal arterioles in the guinea pig ileum. The outside diameter of arterioles in in vitro submucosal preparations from milk-sensitized guinea pigs was monitored using videomicroscopy. Superfusion of the cow's milk protein, beta-lactoglobulin (beta-Lg; 5 microM), evoked large dilations, which became completely desensitized. beta-Lg-evoked dilations were blocked by pyrilamine or NG-monomethyl-L-arginine plus indomethacin but not by TTX. Electron microscopic studies revealed that mast cells, in preparations receiving beta-Lg, demonstrated significant reductions of the dispersed and intact granule areas compared with preparations not exposed to beta-Lg. Paired experiments were conducted to determine if capsaicin-sensitive, nerve-evoked responses involved mast cell degranulation. One preparation received capsaicin (200 nM) followed by beta-Lg (5 microM); the other preparation received the drugs in reverse order. Prior treatment with capsaicin or beta-Lg had no effect on subsequent dilations evoked by the alternate treatment. Electron microscopy showed that nerve-arteriole associations were 10 times closer than nerve-mast cell associations. Mast cell numbers were not increased by milk sensitization. These findings suggest that mast cell- and capsaicin-sensitive nerve-evoked vasodilator mechanisms act independently in a model in which mast cell numbers are not increased.

Alprostadil↗
PubMed1997

CED-4 induces chromatin condensation in Schizosaccharomyces pombe and is inhibited by direct physical association with CED-9.

BACKGROUND: Three principal genes are involved in developmental programmed cell death (PCD) in the nematode worm Caenorhabditis elegans. The ced-3 and ced-4 genes are both required for each PCD, whereas ced-9 acts to prevent the death-promoting actions of these genes in cells that are destined to survive. Vertebrate homologues of both ced-3 and ced-9 have been identified as the genes encoding the caspase cysteine proteases and the Bcl-2 family, respectively. In contrast, no vertebrate homologue of ced-4 is known. The CED-3/caspases are important effectors of apoptosis that are presumed to act by cleaving specific target substrates. However, the molecular functions of the CED-9/Bcl-2 and CED-4 proteins are unknown. The unicellular yeast Schizosaccharomyces pombe shares many general cellular properties with metazoa, but has no identified cell suicide machinery. We have therefore used S. pombe as a naive model cell system in which to examine the biological effects of cell-death proteins. RESULTS: Induction of wild-type ced-4 expression in S. pombe resulted in rapid focal chromatin condensation and lethality. Mutation of the putative nucleotide-binding P-loop motif of CED-4 (K165Q) eliminated the lethal phenotype. Immunolocalization of CED-4 to the condensed chromatin suggested that the phenotype may result from an intrinsic activity of CED-4. Co-expression of ced-9 prevented CED-4-induced chromatin condensation and lethality, and caused the relocalization of CED-4 to endoplasmic reticulum and outer mitochondrial membranes. A direct interaction between CED-4 and CED-9 was confirmed by yeast two-hybrid analysis. CONCLUSIONS: Using S. pombe as a model system in which to assay CED-4 function, we have identified a potential direct role for CED-4 in chromatin condensation. Chromatin condensation is a ubiquitous feature of metazoan apoptosis that has yet to be linked to an effector. The CED-9-mediated rescue of CED-4-induced lethality in this system and the interaction of the two proteins in the yeast two-hybrid analysis suggest that CED-9 inhibits CED-4 action by direct physical association.

Animals↗
PubMed1997

Blood transfusion and chronic lung disease in preterm infants.

UNLABELLED: Frequent blood transfusions may produce changes in iron status which can give rise to oxygen-derived free-radical (ODFR) generation and oxidative injury. Preterm infants developing chronic lung disease (CLD) receive significantly more transfusions. A total of 73 very preterm infants had weekly estimations of serum iron, transferrin, transferrin saturation, ferritin, caeruloplasmin, bleomycin detectable ('free') iron (BDI), and thiobarbituric acid reacting substances (TBARS) made over the first 28 days. Thirty infants remained oxygen dependent at 36 weeks postmenstrual age and were termed as having CLD. They were significantly lighter and less mature at birth and received more than twice as many transfusions during the 1st month. They had significantly lower transferrin levels initially but similar total iron and transferrin saturations as non-CLD infants. Ferritin and caeruloplasmin levels rose to significantly higher levels over the 1st month in CLD infants, and ferritin levels were significantly related to the number of transfusions given. Infants with higher ferritin levels were more likely to show BDI, although this was not associated with increased lipid peroxidation as evidenced by higher TBARS. CONCLUSION: It is unlikely that oxidative injury from ODFRs induced by blood transfusion contributes to the risk of developing CLD in preterm infants.

Bronchopulmonary Dysplasia↗
PubMed1997

Exercise and bone mineral density in mature female athletes.

An understanding of the relationship between weight-bearing activity and bone mineral density (BMD) is important in devising strategies to maximize and maintain skeletal strength in the female population, particularly those entering menopause. Three contrasting groups (N = 20) of mature female athletes (42-50 yr) with long-term (> 20 yr) histories of significant training and performance in their chosen sport were studied cross-sectionally. The groups were: (i) high impact sport (netball/basketball; HIGH), (ii) medium impact sport (running/field hockey; MED) and (iii) a nonimpact sport (swimming; NON) and (iv) a nonsport control group (CON; N = 20). Whole body and regional BMD and body composition (fat and lean mass) were measured by dual-energy x-ray absorptiometry. Isometric strength of dominant arm flexors and leg extensors was measured by a strain tensiometer. With an alpha level of significance of 0.05, HIGH showed significantly greater whole body and regional leg BMD than NON or CON. MED registered higher values than CON for whole body and regional leg BMD. Only HIGH had significantly greater leg strength than CON. Regional arm BMD was significantly greater in all exercising groups compared with CON, but no significant difference in arm strength was found between any groups. The athletic groups all had significantly lower body fat and higher height-corrected lean mass than CON. Height-corrected lean mass, height and leg extensor strength, but not calcium intake, arm flexor strength or body fat, were significant predictors of whole body and regional arm and leg BMD. Using the significant predictors as covariates, the impact groups (HIGH/MED) had significantly higher whole body BMD than CON. HIGH also had significantly higher whole body BMD than NON and both impact groups were greater than NON in regional leg BMD. Results suggest that females who participate regularly in the premenopausal years in high impact physical activity tend to have higher BMD than nonathletic controls.

Absorptiometry, Photon↗
PubMed1997

The purpose of flexible learning in post-registration nurse education.

Post-registration nurse education in England has changed significantly in recent years. One of the most significant changes has been the emergence of flexible learning which is characterized by adaptations in the way programmes are planned, the nature of provision, the ways of enhancing access, the process of teaching and learning, the nature of assessment and the way in which programmes are evaluated. This paper reviews the influences on nurse education at post-registration level which have brought about flexible learning. It analyses the purposes of flexible learning by integrating theoretical considerations and the outcomes of the case study of programmes and modules deemed by providers to be flexible. The over-arching purpose of flexible learning is the improvement of educational quality, specifically in relation to improving access, availability, relevance, and the way in which individual practitioners' needs and importantly the needs of other stakeholders (for example, providers, employers and validating bodies) are met. Flexible learning is also concerned with encouraging self-direction in professional learning. The different purposes and the way in which they interrelate, together with the range of different stakeholders and their potentially conflicting needs, significantly complicates the management of flexible learning.

Curriculum↗
PubMed1997

Human Bak induces cell death in Schizosaccharomyces pombe with morphological changes similar to those with apoptosis in mammalian cells.

Apoptosis as a form of programmed cell death (PCD) in multicellular organisms is a well-established genetically controlled process that leads to elimination of unnecessary or damaged cells. Recently, PCD has also been described for unicellular organisms as a process for the socially advantageous regulation of cell survival. The human Bcl-2 family member Bak induces apoptosis in mammalian cells which is counteracted by the Bcl-x(L) protein. We show that Bak also kills the unicellular fission yeast Schizosaccharomyces pombe and that this is inhibited by coexpression of human Bcl-x(L). Moreover, the same critical BH3 domain of Bak that is required for induction of apoptosis in mammalian cells is also required for inducing death in yeast. This suggests that Bak kills mammalian and yeast cells by similar mechanisms. The phenotype of the Bak-induced death in yeast involves condensation and fragmentation of the chromatin as well as dissolution of the nuclear envelope, all of which are features of mammalian apoptosis. These data suggest that the evolutionarily conserved metazoan PCD pathway is also present in unicellular yeast.

Apoptosis↗
PubMed1997

Clarity of purpose and administrative accountability: an empirical study in long-term residential care.

Experienced social workers in an Australian residential aged care facility mounted a practice research project over three years. Aims included meeting agency accountability requirements and illustrating social work roles. In consultation with a university school of social work lecturer, the staff members devised a tool to document their practice on a per case basis across the care continuum as well as non case-related work associated with resident needs and agency purpose. A three-month pilot indicated that casework comprised 70% of work time, the 405 cases incorporating higher than expected time on preadmission, gatekeeping and admission tasks. Analyses of the most time-consuming cases revealed complex interacting factors inadequately captured by available and physically-driven case classification and costing tools.

Aged↗
PubMed1997

Intervention strategies to enhance anatomical plasticity and recovery of function after spinal cord injury.

Taken together, our studies indicate that (a) transplants mediate recovery of skilled forelimb movement as well as locomotor activity, (b) combinations of interventions may be required to restore reflex, sensory, and locomotor function to more normal levels after SCI, and (c) that remodeling of particular pathways may contribute to recovery of rather specific aspects of motor function. In conclusion, we suggest that it seems unlikely that any single intervention strategy will be sufficient to ensure regeneration of damaged pathways and recovery of function after SCI. Clearly, work from a number of laboratories indicates that the dogma that mature CNS neurons are inherently incapable of regeneration of axons after injury is no longer tenable. The issue, rather, is to identify and reverse the conditions that limit regeneration after SCI. After SCI, a hierarchy of "intervention-strategies" may be required to restore suprasegmental control leading to recovery of function. The hierarchy may be both temporal and absolute. For example, early interventions (such as the administration of methylprednisolone within hours of the injury) may be required to interrupt the secondary injury cascade and restrict the extent of damage after SCI. At the injury site itself, interventions to minimize the secondary injury effects may be followed by interventions to alter the environment at the site of injury to provide a terrain conducive to axonal elongation. For example, one might envision strategies to downregulate the expression of molecules that limit growth and upregulate the expression of those that support growth. Early after the injury, axotomized neurons may require neurotrophic support either for their survival or to initiate and maintain a cell body response supporting axonal elongation. There may be an absolute hierarchy as well. Particular populations of neurons may have very specific requirements for regenerative growth. For example, the conditions that enhance the regenerative growth of descending motor pathways may differ from those required by ascending sensory systems. One may also want to design strategies to restrict the plasticity of some pathways (e.g., nociceptive) and enhance the growth in other pathways. The demands on the CNS for anatomic reorganization after SCI may be far less formidable than one might at first imagine. If one assumes that recovery of function will require regenerative growth of large numbers of axons over long distances in a point-to-point topographically specific fashion, the idea of recovery of function becomes daunting. On the other hand, it has been shown in many studies and in many areas of the CNS that as little as 10% of a particular pathway can often subserve substantial function. Furthermore, regrowth over relatively short distances can have major functional consequences. For example, relatively modest changes in the level of SCI can have relatively profound effects on the functional consequences of injury. This is particularly true in cervical SCI: an individual with a C5/6 SCI is dramatically more impaired than one with C7/8 injury. One might envision relatively short distance growth across the injury site to re-establish suprasegmental control. Coupled with strategies to enhance the anatomic and functional reorganization of spinal cord circuitry caudal to the level of the injury, even modest long distance growth may have sufficient functional impact. One might imagine the ability to learn to "use" even modest quantities of novel inputs in functionally useful, appropriate ways.

Animals↗
PubMed1997

Speech perception in noise with implant and hearing aid.

OBJECTIVE: To compare the perception of speech in quiet and in noise by adults using a cochlear implant on its own or a cochlear implant and hearing aid together. STUDY DESIGN: Repeated measures. SETTING: Laboratory study using subjects' own speech processors. PATIENTS: Two groups of cochlear implant users (Australian and American) with some residual hearing in the non-implanted ear (pure tone average thresholds at 500 Hz, 1 kHz, and 2 kHz of 75-112 dB HL). INTERVENTION(S): Conventional hearing aid and cochlear implant in opposite ears. MAIN OUTCOME MEASURES: Speech perception was evaluated using recorded lists of CUNY sentences and lists of CNC words in quiet and in background noise. RESULTS: Speech scores were significantly higher with implant and hearing aid together compared to implant alone. The binaural advantage was greater in background noise than it was in quiet for CUNY sentences in the American listeners. CONCLUSION: Severely-to-profoundly hearing impaired adults may benefit from combined fitting of implants and conventional hearing aids in opposite ears.

Adult↗
PubMed1996

Betulinic acid derivatives: a new class of human immunodeficiency virus type 1 specific inhibitors with a new mode of action.

A series of omega-undecanoic amides of lup-20(29)-en-28-oic acid derivatives were synthesized and evaluated for activity in CEM 4 and MT-4 cell cultures against human immunodeficiency virus type 1 (HIV-1) strain IIIB/LAI. The potent HIV inhibitors which emerged, compounds 5a, 16a, and 17b, were all derivatives of betulinic acid (3beta-hydroxylup-20(29)-en-28-oic acid). No activity was found against HIV-2 strain ROD. Compound 5a showed no inhibition of HIV-1 reverse transcriptase activity with poly(C).oligo(dG) as template/primer, nor did it inhibit HIV-1 protease. Additional mechanistic studies revealed that this class of compounds interfere with HIV-1 entry in the cells at a postbinding step.

Antiviral Agents↗
PubMed1996

Reflective practice: reviewing the issues and refocusing the debate.

Reflective practice has emerged in the U.K. and beyond as an important issue not just in nursing but in many other professions. However, it remains problematic; it is difficult to conceptualize and many aspects of it are open to debate. Reflective practice is also contentious because, at a fundamental level, it raises a number of important issues for professional practitioners and the way they view their practice. The intention of this paper is to: explore some of the issues that have emerged as the profession of nursing and other professions have gained a better understanding of reflective practice; broaden the scope of the debate and refocus it; raise issues which are in need of further research.

Holistic Nursing↗