Biomedical subjects

L S Jones

Publications and source records attributed to L S Jones.

At least 19 recordsLinked to original sources

PubMed2005

Primary malignant melanoma of the colon in an oculocutaneous albino.

We describe the case of an elderly albino man who presented with the typical features of a caecal malignancy and underwent a right hemi-colectomy. Histological assessment subsequently revealed the tumour to be a primary malignant melanoma of the colon. This unexpected diagnosis raises interesting questions regarding the embryology and aetiology of this rare tumour and the anticipated prognosis. To the best of our knowledge, this is the first reported case of a primary colonic melanoma associated with oculocutaneous albinism.

Aged↗

PubMed2004

Stoma formation for functional bowel disease.

OBJECTIVE: To assess the results of stoma formation for functional bowel disease. METHODS: A retrospective study of the indications for and complications of stoma formation in this group. A quality of life questionnaire was sent to the group. RESULTS: A very small proportion of patients with functional bowel disease have a stoma formed (< 1%). Stoma formation is often associated with problems requiring further operations. Their QOL is reported as poor and is improved upon by stoma formation. Most patients with a temporary stoma elected to keep it rather than suffer their previous problems. CONCLUSION: Some patients with functional bowel disease can be successfully managed by stoma formation. Their treatment is difficult, emotionally demanding and labour-intensive.

Adolescent↗

PubMed2002

Sex differences in hippocampal slice excitability: role of testosterone.

In vivo fluctuations in gonadal hormones alter hippocampal excitability and modulate both physiological and pathological hippocampal processes. To assess hormonal effects on excitability within a functional hippocampal circuit, extracellular CA1 field responses were compared in slices from intact male, intact female, orchidectomized male, and ovariectomized female rats. Secondly, the effects of in vitro applications of 17-beta estradiol, progesterone, or testosterone on baseline excitability of slices from gonadectomized rats were assessed versus pre-hormone baseline measures. Finally, using the in vitro kindling model of slice epileptogenesis, steroid hormone effects on interictal-like activity were also examined. Significant sex differences in excitatory postsynaptic potential amplitude were observed, with slices from males having larger excitatory postsynaptic potential amplitudes than those from females. Gonadectomy significantly decreased excitatory postsynaptic potential amplitude in slices from male rats. Slices from gonadectomized male and female rats also showed a decreased dendritic excitatory postsynaptic potential slope relative to slices from intact male and females rats. In vitro application of testosterone significantly increased excitatory postsynaptic potential amplitudes in slices from both orchidectomized males and ovariectomized females and the population spike amplitude of slices from ovariectomized females. Following in vitro kindling, slices from intact males showed greater spontaneous burst rates than slices from intact females, further suggesting an excitatory effect of testosterone. These results suggest: (1) a sex difference in the level of baseline excitability between slices from intact males and females as measured by excitatory postsynaptic potential amplitudes, (2) testosterone has excitatory effects on baseline physiology and kindled hippocampal responses, and (3) slices from males show a greater level of excitability than those from females in the in vitro kindling model.

Action Potentials↗

PubMed2001

Anti-epileptiform effects of audiogenic seizure priming on in vitro kindling in rat hippocampus.

The effect of priming for audiogenic seizures (AGS) on the development of epileptiform activity in the hippocampus was studied using in vitro kindling (IVK) in Long-Evans rats. AGS priming consists of intense auditory stimulation during a critical period of auditory development, resulting in sound-induced clonic convulsions upon subsequent testing. Between postnatal day (PND) 28 and 50, slices from subjects primed and sham-primed for AGS on PND 18 were used for recording responses in area CA1 of hippocampus following Schaffer collateral stimulation from stratum radiatum of area CA2/CA3. The developmental priming procedure, which enhances auditory brainstem excitability, resulted in fewer afterdischarges in slices from primed subjects across initial IVK stimulation sequences. These results suggest that changes in excitability that occur with acoustic priming can initially diminish selective epileptiform response characteristics in forebrain areas such as the hippocampus.

Acoustic Stimulation↗

PubMed2001

The effects of Tween 20 and sucrose on the stability of anti-L-selectin during lyophilization and reconstitution.

We have chosen an anti-L-selectin antibody as a model protein to investigate the effects of sucrose and/or Tween 20 on protein stability during lyophilization and reconstitution. Native anti-L-selectin secondary structure is substantially retained during lyophilization in the presence of sucrose (1 or 0.125%). However, aggregation of the protein during reconstitution of lyophilized protein powders prepared without sucrose is not reduced by the presence of sucrose in the reconstitution medium. Aggregate formation upon reconstitution is completely inhibited by freeze drying the protein with sucrose and reconstituting with a 0.1% Tween 20 solution. Tween 20 (0.1%) also partially inhibits loss of native anti-L-selectin secondary structure during lyophilization. However, upon reconstitution the formulations lyophilized with Tween 20 contain the highest levels of aggregates. The presence of Tween in only the reconstitution solution appears to inhibit the transition from dimers to higher order oligomers. Potential mechanism(s) for the Tween 20 effects were investigated. However, no evidence of thermodynamic stabilization of anti-L-selectin conformation (e.g., by Tween 20 binding) could be detected.

Antibodies, Monoclonal↗

PubMed2001

Anaesthesia for caesarean section in a patient with Ehlers-Danlos syndrome and mitral valve prolapse.

We report the successful use of single-shot spinal anaesthesia for elective caesarean section in a multigravid woman with Ehlers-Danlos syndrome, complicated by mitral valve prolapse. This is a rare inherited collagen disorder that has been reported to have a high pregnancy-related morbidity and mortality, particularly from uterine rupture and uncontrolled bleeding from friable vessels, coagulopathy and major vessel rupture. The literature concerning obstetric anaesthetic management for different types of Ehlers-Danlos syndrome and the management of mitral valve prolapse in pregnancy are reviewed.

Journal Article↗

PubMed2001

Experience with a one-stop colorectal clinic.

BACKGROUND AND OBJECTIVE: Colorectal services have traditionally been arranged for the convenience of hospitals rather than patients. This model is not ideal, particularly for minor interventions and diagnostic procedures. In order to address this a one-stop colorectal clinic was set up. PATIENTS AND METHODS: Weekly clinics ran from 6.00 to 9.30 p.m. on Wednesdays for a period of 6 months. Patients with rectal bleeding, altered bowel habit, anorectal symptoms and those requesting screening advice were seen by a consultant or specialist registrar. Patients were asked to fill in a questionnaire at the end of their clinic attendance. RESULTS: 197 patients were seen in 17 clinics; 134 underwent proctoscopy, 72 had a rigid sigmoidoscopy and 85 had a flexible sigmoidoscopy carried out. Twenty-four patients subsequently had a barium enema and 3 were listed for colonoscopy. The main diagnosis was haemorrhoids (n = 104); 14 colorectal neoplasms were discovered (5 cancers and 9 polyps). During the study period the number of patients waiting for lower gastrointestinal endoscopy fell from 119 to 63; 2 months after ending the pilot scheme, the number had risen to 108. CONCLUSION: The clinic was found to have significantly improved patient care. The majority of patients were satisfied with an evening clinic. Flexible sigmoidoscopy without sedation was well tolerated and the ability to perform this at initial assessment had a marked effect on the number of patients awaiting lower gastrointestinal endoscopy.

Ambulatory Care Facilities↗

PubMed2000

Effect of zinc binding and precipitation on structures of recombinant human growth hormone and nerve growth factor.

Metal-induced precipitation of protein therapeutics is being used and further developed as a processing step in protein formulation and may have utility in protein purification and bulk storage. In such processes, it is imperative that native protein structure is maintained and the metal complexation is reversible. In the current study, we investigated the effects of zinc-induced precipitation on recombinant human growth hormone (rhGH) and recombinant human nerve growth factor (rhNGF). On the addition of ethylenediaminetetraacetic acid (EDTA), the precipitates were dissolved, yielding complete recovery of native protein in both cases. Both proteins have specific metal binding sites and require specific molar ratios of zinc to protein to initiate precipitation (zinc:rhGH > 2:1; zinc:rhNGF > 18:1). Furthermore, the secondary structures of both proteins were unperturbed in soluble zinc complexes and zinc-induced precipitates, as measured by infrared and circular dichroism spectroscopies. The soluble zinc complex of rhGH had minor tertiary structural alterations, whereas zinc binding did not alter the tertiary structure of rhNGF. These studies indicated that metal-induced precipitation provides a method to maintain proteins in their native state in precipitates, which may be useful for purification, storage, and formulation.

Binding Sites↗

PubMed2000

Plastic bag asphyxia in southeast Scotland.

Death resulting from plastic bag asphyxia has been recognized for >40 years, but relatively little is known about either its epidemiology or its pathophysiology. Over 15 years (1984-1998), 30 deaths were attributed to plastic bag asphyxia among the 14,560 autopsies performed in the Forensic Medicine Unit in Edinburgh. These 30 deaths involved 20 male and 10 female subjects, with an age range of 13 to 81 years. Eleven had some alcohol measurable in the blood, with four having levels >80 mg/dl. Only one individual appeared to have ingested a drug overdose, but inhaled substances within the plastic bag may have contributed to death in five cases. The absence of childhood accidental deaths may reflect successful preventive measures. The 3 accidental deaths involved adults (including 2 who died of autoerotic asphyxia), and the remaining deaths were 27 suicides. Of those who committed suicide, most (59%) had chronic psychiatric illness rather than chronic debilitating or terminal physical illness. In contrast with reports from the United States, publicity associated with "self-deliverance" did not result in an increased number of deaths from plastic bag asphyxia (4 deaths in this series). Analysis of the circumstances of all the deaths revealed them to be difficult to predict and hence prevent.

Accidents↗

PubMed2000

Attitudes of psychologists and psychologists-in-training to homosexual women and men: an Australian study.

Homophobic reactions of Australian psychologists (n = 43), postgraduate psychology students (n = 17) and undergraduate psychology students (n = 44) were compared using Van de Ven's (1994) measures of cognitive, affective and behavioral dimensions of homophobia. Results suggested that undergraduates were significantly more homophobic than psychologists in their thinking, intentional behavior and feelings of fear or discomfort in relation to lesbians and gay men. No other significant group differences were found. Gender differences were found only in relation to one affective dimension of homophobia. Low levels of positive affective response to homosexuals were observed across groups and gender. The study underscores the importance of assessing homophobic response multidimensionally. Implications for the training of Australian psychologists are discussed.

Adult↗

PubMed2000

Fatigue patterns observed in patients receiving chemotherapy and radiotherapy.

The purpose of this study was to describe the patterns of cancer-related fatigue (CRF) and vigor in patients receiving chemotherapy or radiation therapy. Five studies that measured fatigue and vigor with the Profile of Mood States were used to describe the pattern of CRF and vigor during and after both types of treatment. Repeated-measures ANOVA was used to determine differences over time in each study. Results demonstrate different patterns of CRF for patients receiving chemotherapy and radiation therapy. Chemotherapy-related CRF peaks in the days after chemotherapy, whereas radiation therapy-related CRF gradually accumulates over the course of treatment. The CRF associated with both forms of treatment gradually declines over time. The prevalence, intensity, and persistence of CRF during treatment and for months after treatment is complete make this symptom one that cannot be ignored.

Adolescent↗

PubMed1999

Investigation of protein-surfactant interactions by analytical ultracentrifugation and electron paramagnetic resonance: the use of recombinant human tissue factor as an example.

PURPOSE: The purpose of this work is to utilize electron paramagnetic resonance (EPR) spectroscopy in conjunction with analytical ultracentrifugation (AUC) to investigate the binding of surfactants to proteins with a transmembrance domain. As an example these methods have been used to study the interaction of a nonionic surfactant, C12E8, to recombinant human tissue factor (rhTF) in liquid formulations. The complementary nature of the two techniques aids in data interpretation when there is ambiguity using a single technique. In addition to binding stoichiometries, the possibility of identifying the interacting domains by using two forms of rhTF is explored. METHODS: Two recombinant, truncated forms of human tissue factor were formulated in the absence of phospholipids. Neither of the recombinant proteins, produced in E. coli, contains the cytoplasmic domain. Recombinant human tissue factor 243 (rhTF 243) consists of 243 amino acids and includes the transmembrane sequences. Recombinant human tissue factor 220 (rhTF 220), however, contains only the first 221 amino acids of the human tissue factor, lacking those of the transmembrane region. EPR and AUC were used to investigate the interactions between these two forms of rhTF and polyoxyethylene 8 lauryl ether, C12E8. RESULTS: Binding of C12E8 to rhTF 243 is detected by both EPR spectroscopy and AUC. Although a unique binding stoichiometry was not determined, EPR spectroscopy greatly narrowed the range of possible solutions suggested by the AUC data. Neither technique revealed an interaction between rhTF 220 and C12E8. CONCLUSIONS: The complementary nature of EPR spectroscopy and AUC make the combination of the two techniques useful in data interpretation when studying the interactions between rhTF and C12E8. By utilizing these techniques in this study, the binding stoichiometry of rhTF 243 to C12E8 ranges from 1.2:1 to 1.3:0.6 based on an aggregation number of 120. This binding is consistent with previously reported activity data that showed an increase in clotting rate when rhTF 243 is in the presence of C12E8 micelles. From the rhTF 220 data, it can further be concluded that the transmembrane domain of rhTF is necessary for interactions with C12E8.

Electron Spin Resonance Spectroscopy↗

PubMed1998

Effect of Tween 20 on freeze-thawing- and agitation-induced aggregation of recombinant human factor XIII.

Agitation- and freeze-thawing-induced aggregation of recombinant human factor XIII (rFXIII) is due to interfacial adsorption and denaturation at the air-liquid and ice-liquid interfaces. The aggregation pathway proceeds through soluble aggregates to formation of insoluble aggregates regardless of the denaturing stimuli. A nonionic surfactant, polyoxyethylene sorbitan monolaurate (Tween 20), greatly reduces the rate of formation of insoluble aggregates as a function of surfactant concentration, thereby stabilizing native rFXIII. Maximum protection occurs at concentrations close to the critical micelle concentration (cmc), independent of initial protein concentration. To study the mechanistic aspects of the surfactant-induced stabilization, a series of spectroscopic studies were conducted. Electron paramagnetic resonance spectroscopy indicates that binding is not occurring between Tween 20 and either the native state or a folding intermediate state of rFXIII. Further, circular dichroism spectroscopy suggests that Tween 20 does not prevent the secondary structural changes induced upon guanidinium hydrochloride-induced unfolding. Taken together, these results imply that Tween 20 protects rFXIII against freeze-thawing- and agitation-induced aggregation primarily by competing with stress-induced soluble aggregates for interfaces, inhibiting subsequent transition to insoluble aggregates.

Circular Dichroism↗

PubMed1998

Planning and conducting a multi-institutional project on fatigue.

PURPOSE/OBJECTIVES: To describe the process used in proposal development and study implementation for a complex multisite project on cancer treatment-related fatigue (CRF), identify strategies used to manage the project, and provide recommendations for teams planning multisite research. DATA SOURCES: Information derived from project team meeting records, correspondence, proposals, and personal recollection. DATA SYNTHESIS: The project was built on preexisting relationships among the three site investigators who then built a team including faculty, research coordinators, staff nurses, and students. Study sites had a range of organizational models, and the proposal was designed to capitalize on the organizational and resource strengths of each setting. Three team members drawn from outside oncology nursing provided expertise in measurement and experience with fatigue in other populations. Planning meetings were critical to the success of the project. Conference calls, fax technology, and electronic mail were used for communication. Flexibility was important in managing crises and shifting responsibility for specific components of the work. The team documented and evaluated the process used for multisite research, completed a major instrumentation study, and developed a cognitive-behavioral intervention for CRF. CONCLUSIONS: Accomplishments during the one-year planning grant exceeded initial expectations. The process of conducting multisite research is complex, especially when the starting point is a planning grant with specific research protocols to be developed and implemented over one year. Explicit planning for decision-making processes to be used throughout the project, acknowledging the differences among the study settings and planning the protocols to capitalize upon those differences, and recruiting a strong research team that included a member with planning grant and team-building expertise were essential elements for success. IMPLICATIONS FOR NURSING PRACTICE: Specific recommendations for others planning multisite research are related to team-building, team membership, communication, behavioral norms, role flexibility, resources, feedback, problem management, and shared recognition.

Communication↗

PubMed1997

RGDS tetrapeptide and hippocampal in vitro kindling in rats: evidence for integrin-mediated physiological stability.

We have examined a potential role for integrins in an animal model of epileptogenesis termed in vitro kindling. Integrins mediate cell-cell and cell-matrix interactions, and also participate in the transduction of information from the extracellular environment to the intracellular milieu. As many extracellular matrix (ECM) molecules contain the conserved amino acid sequence arg-gly-asp-ser (RGDS) at the integrin recognition site, integrin-ECM binding can be disrupted using RGDS peptides. Hippocampal slices were washed in either RGDS, gly-gly-gly-gly (GGGG), vehicle or artificial cerebral spinal fluid (ACSF) for 1 h prior to in vitro kindling. Baseline electrophysiological responses were unaltered by RGDS peptide. The RGDS-treated slices displayed a significant decrease in the rate of spontaneous bursts, whereas the period of spontaneous bursting increased dramatically. Our results indicate that the competitive peptide, RGDS, changed hippocampal slice excitability over time, indicating that interference with ECM-integrin binding may alter neuronal signaling through an RGDS binding site.

Animals↗

PubMed1997

IFN-gamma-deficient mice develop experimental autoimmune uveitis in the context of a deviant effector response.

Experimental autoimmune uveitis (EAU) is a T cell-mediated disease that targets the neural retina and serves as a model of human uveitis. Uveitogenic effector T cells have a Th1-like phenotype (high IFN-gamma, low IL-4), and genetic susceptibility to EAU is associated with an elevated Th1 response. Here we investigate whether the ability to produce IFN-gamma is necessary for the development of EAU by immunizing IFN-gamma-deficient (GKO) mice with the uveitogenic protein interphotoreceptor retinoid binding protein (IRBP) and characterize the associated immunologic responses. GKO mice developed EAU comparable in severity and incidence to that of their wild-type littermates. However, the cytokine profile in their uveitic eyes as well as the cytokines produced by primed lymph node cells in response to IRBP showed a distinct profile: undiminished TNF-alpha and elevated IL-5, IL-6, IL-10, and lymphotoxin (but not IL-4) responses. The inflammatory infiltrate in GKO eyes contained an excess of granulocytes and IL-5- and IL-6-producing cells, but uveitic GKO mice did not up-regulate inducible nitric oxide synthase. GKOs had enhanced lymphocyte proliferation and delayed-type hypersensitivity responses to IRBP. Histology of the delayed-type hypersensitivity lesion in GKO had superimposed elements of an allergic-like response. Anti-IRBP Ab isotypes of GKO mice showed a reduction of IgG2a, but no enhancement of IgG1. Comparison of responses in +/+ and +/- wild-type mice revealed some limited evidence of a gene-dose effect. We conclude that IFN-gamma is not required for priming of pathogenic T cells or for effecting the retinal damage and photoreceptor loss typical of EAU. However, what appears to be a grossly similar disease is caused in the GKO by a deviant type of effector response.

Animals↗

PubMed1997

Inhibition of LTB4 biosynthesis in situ by CGS 23885, a potent 5-lipoxygenase inhibitor, correlates with its pleural fluid concentrations in an experimentally induced rat pleurisy model.

An intrapleural injection of carrageenan in rats induced LTB4 and LTC4/D4/E4 biosynthesis, exudate formation, and cellular influx in the pleural cavity. An injection of calcium ionophore (A23187, 100 nmol) 16-18 h after carrageenan injection augmented leukotriene biosynthesis and exudate formation, but not cellular influx. The carrageenan-induced pleurisy model modifid by A23187 administration was used to study the oral effect of CGS 23885 (N-hydroxy-N-[(6-phenoxy-2H-1-benzopyran-3-yl)-methyl]urea), a potent 5-lipoxygenase (5-LO) inhibitor, on inflammatory parameters. CGS 23885 dose-dependently (1 to 30 mg/kg) inhibited the enhanced LTB4 and LTC4/D4/E4 (1 to 10 mg/kg) biosynthesis, but had no effect on enhanced exudate formation. An inhibitory effect of CGS 23885 of small magnitude on cellular influx due to carrageenan stimulation was seen at 30 mg/kg. The concentrations of CGS 23885 in the pleural fluid were dose-related, and a positive correlation (r2=0.989) between pleural fluid concentration of LTB4 and CGS 23885 was observed. The results confirm that CGS 23885 is a specific, orally active 5-LO inhibitor which can achieve concentrations in the pleural cavity sufficient to inhibit production of LTB4 and LTC4/D4/E4 in an ongoing inflammatory response.

Animals↗

PubMed1997

Normal and aberrant functions of integrins in the adult central nervous system.

Integrins are heterodimeric proteins mediating cell-cell and cell-extracellular matrix adhesive connections (Springer T.A., 1990, Nature 346, 425-434) and signal transduction across the plasma membrane. The important roles of integrins in neural development and cancer, where they subserve process outgrowth and cell migration, are well documented, but information on integrins in the adult central nervous system has been slower to arrive. Now that strong evidence, both molecular biological and immunocytochemical, has been collected, it is useful to speculate on what these interesting proteins may be doing in the adult central nervous system. Suggestive data now points to roles in functions characterized in part by morphological rearrangements, such as learning and memory, and injury responses.

Animals↗