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T Stewart

Publications and source records attributed to T Stewart.

At least 37 records · Page 2Linked to original sources
PubMed2000

Phenotypic characterization of immortalized normal and primary tumor-derived human prostate epithelial cell cultures.

BACKGROUND: Cell lines can provide powerful model systems for the study of human tumorigenesis. However, the human prostate cancer cell lines studied most intensively by investigators (PC3, DU145, and LNCaP) were established from metastatic lesions, and it is unlikely that they accurately recapitulate the genetic composition or biological behavior of primary prostate tumors. Cell lines more appropriate for the study of human prostate primary tumors would be those derived from spontaneously immortalized cells; unfortunately, explanted prostate cells survive only short-term in culture, and rarely immortalize spontaneously. Therefore, we examined whether cell lines developed through viral gene-mediated immortalization of human normal or primary tumor prostate epithelium express aspects of the normal or malignant phenotypes, and could serve as appropriate models for normal or transformed human prostatic epithelium. METHODS: To accomplish these goals, we assessed the phenotypic expression of cell cultures established through the immortalization of normal (1532N, 1535N, 1542N, and PrEC-T) or malignant (1532T, 1535T, and 1542T) human prostate epithelium with the E6 and E7 genes of HPV-16, or the large T antigen gene of SV40. RESULTS: Examination of these cell lines for their proliferative rates and their abilities to grow with or without serum or androgen stimulation, to form colonies in soft agar, or to form tumors in vivo, suggests that they may serve as valid, useful tools for the elucidation of prostate tumorigenesis. Moreover, the observation of structural alterations involving chromosome 8, including gain of 8q in 3 of the 4 cell lines expressing aspects of the malignant phenotype, implies that these cell lines accurately recapitulate the genetic composition of primary prostate tumors. CONCLUSIONS: Taken together, these data suggest that cell lines generated from immortalized normal or primary tumor epithelium may be useful for the elucidation of early transforming events in the prostate.

Animals↗
PubMed2000

A phase I trial of solubilized DR2:MBP84-102 (AG284) in multiple sclerosis.

OBJECTIVE: To assess the safety, tolerability, and biologic and clinical activity of a solubilized complex comprised of human leukocyte antigen-DR2 with myelin basic protein84-102 (AG284)in patients with secondary progressive MS. BACKGROUND: Soluble species-specific major histocompatibility complex myelin basic protein91-103 complexes ameliorate disease in a dose-dependent manner when administered to SJL/J mice with chronic relapsing experimental allergic encephalomyelitis. Preincubation with AG284 reduces the proliferative response of a DR2-restricted, myelin basic protein84-102-reactive T cell clone, derived from a MS patient, to myelin basic protein84-102 in the presence of autologous antigen-presenting cells. METHODS: Thirty-three patients with secondary progressive MS were randomly assigned to receive three alternate day IV doses of AG284 or placebo in a double-masked dose escalation study. The primary outcome was safety and tolerability. Secondary outcomes included a comparison of pre- and post-treatment gadolinium-enhanced brain MRI activity, Kurtzke Expanded Disability Status Scale, and Nine Hole Peg Test scores. RESULTS: The frequency of adverse events was similar in the AG284 and placebo recipients. No significant treatment effect was detected by Expanded Disability Status Scale, Nine Hole Peg Test, or number of new gadolinium-enhancing MRI lesions. CONCLUSIONS: AG284 as administered during this study was safe and well tolerated. Further studies are warranted to determine the biologic activity and clinical efficacy of this potential treatment for MS.

Adult↗
PubMed2000

Ergonomics user interface standards: are they more trouble than they are worth?

The purpose of this paper is to review the history, progress and results of one area of international standardization--the ergonomics of human-system interaction. It is a personal perspective based on my experiences as Chairman of ISO/TC159/SC4 over the past 17 years. The paper starts with some historical background and summarizes the main work of the Committee. It then identifies five areas where the results of the standardization work could have been more successful and discusses what went wrong. These problems include the long time-scale for development, how the standards were misunderstood, how political the process can be, how we may have tried to be too clever and how the abundance of help at times may have been a problem. The paper concludes with an explanation of why the activity and the results were not all bad. The five positive areas include the benefits that can come from the slow pace of the work, the benefits of structure and formality, why standards do not have to be restrictive, how the standards themselves are only part of the outcome and how being a truly international experience makes it all worthwhile.

Ergonomics↗
PubMed2000

Dengue surveillance in the Pacific Islands.

Adequate monitoring of dengue activity can be achieved using a combination of mosquito vector surveillance, fever surveillance, sentinel clinicians and laboratory screening. An apparent increase in fever cases or clinically suspected DF should prompt a careful clinical and laboratory investigation. If an outbreak of dengue is confirmed, health authorities will need to implement emergency community-wide control strategies. Laboratories will quickly feel the burden of clinical monitoring of cases admitted with DHF/DSS. Surveillance can change to clinical case definitions as health workers become familiar with the presenting features of DF and DHF/DSS. Criteria for hospital referral and admission must be well understood. Routine laboratory and sentinel surveillance may resume as the epidemic wanes, and should then continue indefinitely to monitor any resurgence of dengue activity.

Dengue↗
PubMed1999

Serum MMP-9 and TIMP-1 levels are related to MRI activity in relapsing multiple sclerosis.

OBJECTIVE: To 1) compare monthly serum levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP-type 1 (TIMP-1) in patients with relapsing-remitting MS (RRMS) versus healthy controls and 2) determine the relationship among monthly serum levels of MMP-9 and TIMP-1 and MRI activity. BACKGROUND: Activated T-cells and macrophages secrete MMPs that may facilitate their migration across vascular subendothelial basement membranes into the CNS. The serum concentration of MMP-9 is reported to be higher in patients with RRMS than healthy controls. METHODS: Monthly evaluations including gadolinium-enhanced (Gd+) brain MRI and measures of serum MMP-9 and TIMP-1 were performed for up to 15 months in 24 patients with RRMS and for up to 4 months in 10 controls. RESULTS: Serum MMP-9 but not TIMP-1 levels are elevated in RRMS patients compared to healthy controls (p = 0.025, p = 0.61). In a univariate analysis, high MMP-9 and low TIMP-1 levels precede appearance of new Gd+ lesions (respectively; odds ratio = 3.3, p = 0.008; odds ratio = 2.2, p = 0.086). In a multivariate analysis, in comparison to months when MMP-9 is low and TIMP-1 high, MRI scans obtained the month following high MMP-9 and low TIMP-1 serum concentrations are more likely to report new Gd+ lesions (p = 0.0006, odds ratio = 21.5). CONCLUSION: An increase in the activity of matrix metalloproteinase-9 (MMP-9) relative to tissue inhibitor of MMP-type 1 (TIMP-1) may be related to formation of new MS lesions, suggesting that serum levels of MMP-9 and TIMP-1 may be surrogate markers of disease activity in relapsing-remitting MS.

Adolescent↗
PubMed1999

At-birth immunisation against hepatitis B using a novel pre-filled immunisation device stored outside the cold chain.

We evaluated the immunogenicity of hepatitis B (HB) vaccine in UniJect, a pre-filled, non-reusable injection device, stored at tropical temperatures for up to one month and used to give the first dose of HB vaccine to newborns. Infants in Tabanan district, Bali, Indonesia, were given their first dose of HB vaccine with UniJect stored out of the cold chain, UniJect stored in the cold chain; or standard syringe, needle and multidose vial stored in the cold chain. Subsequent doses were given by usual means and blood samples drawn 4-6 weeks after the third dose. No significant differences were found in seroconversion rates or geometric mean titres of HB surface antibody between the three groups.

Cold Temperature↗
PubMed1999

Characterization of T-lymphocytes in the anterior uvea of eyes with chronic equine recurrent uveitis.

Equine recurrent uveitis (ERU), a chronic, recurrent inflammation primarily of the anterior uveal tract, is the most common cause of blindness in horses. Recently, T-lymphocytes have been found to be the most numerous cell type to infiltrate the anterior uveal of horses with ERU. In the present study, we characterized the T-lymphocyte population in the anterior uveal tract of eyes of horses with chronic ERU by evaluating the microscopic appearance (histopathologic features), the T-lymphocyte subsets, and the relative levels and amounts of T-lymphocyte cytokine mRNA in the anterior uvea. Seven inflamed eyes (from six horses with chronic ERU) and 5 normal eyes (from five horses with nonocular problems) were studied. After clinical examination, the eyes were removed, ocular fluids were aspirated, and anterior uveal tissues (iris and ciliary body) were processed for histologic and molecular (RNA isolation) analyses. Histologic examination by hematoxylin and eosin (H and E) staining and immunohistochemistry evaluating T-lymphocyte subsets (anti-CD4, CD8, CD5) were performed for each sample. RNA samples were analyzed for levels of messenger (m) RNA specific for interleukin (IL)-2, 4, and interferon-gamma (IFNgamma) by quantitative reverse transcriptase polymerase chain reaction (QRT-PCR). Eyes with ERU exhibited characteristic clinical signs, including corneal edema, aqueous flare, posterior synechia, corpora nigra degeneration, and cataract formation. Histologically, infiltration of the uveal tract with lymphocytes, plasma cells, and macrophages was most evident in the ciliary body and base of the iris. Loss of tissue structure (destruction) was most evident in the ciliary processes. Infiltrating lymphocytes were predominantly CD4+ T-cells (e.g. 48% CD4+ and 18% CD8+ in the ciliary body stroma), as determined by immunohistochemistry. Few inflammatory cells were observed in the normal eyes. The QRT-PCR results revealed increased transcription of IL-2 and IFNgamma and low IL-4 mRNA expression in eyes with chronic ERU compared to normal eyes, demonstrating a Thelper (Th) 1-like inflammatory response in eyes with ERU.

Animals↗
PubMed1999

Home delivery of heat-stable vaccines in Indonesia: outreach immunization with a prefilled, single-use injection device.

Extending immunization coverage to underserved populations will require innovative immunization strategies. This study evaluated one such strategy: the use of a prefilled, single-use injection device for outreach immunization by village midwives. The device, UniJect, is designed to prevent refilling or reuse. Stored at ambient temperatures for up to 1 month in midwives' homes, vaccine-filled UniJect devices were immediately available for outreach. Between July 1995 and April 1996, 110 midwives on the Indonesia islands of Lombok and Bali visited the homes of newborn infants to deliver hepatitis B vaccine to the infants and tetanus toxoid to their mothers. Observations and interviews showed that the midwives used the device properly and safely to administer approximately 10,000 sterile injections in home settings. There were no problems with excessive heat exposure during the storage or delivery of vaccine. Injection recipients and midwives expressed a strong preference for the UniJect device over a standard syringe. Use of the prefilled device outside the cold chain simplified the logistics and facilitated the speed and efficiency of home visits, while the single-dose format minimized vaccine wastage.

Adult↗
PubMed1998

Facility with the English language and problem-based learning group interaction: findings from an Arabic setting.

The Faculty of Medicine and Health Sciences (FMHS), United Arab Emirates (UAE) University is in a unique position to explore issues related to English language proficiency and medical student performance. All students entering the FMHS have English as a second language. This study focused on the issues of students' proficiency in English as measured by the TOEFL test, student background factors and interaction in problem-based learning (PBL) groups. Using a modification of Bales Interaction Process Analysis, four problem-based learning groups were observed over four thematic units, to measure the degree of student interaction within PBL groups and to compare this to individual TOEFL scores and key background variables. The students' contributions correlated highly with TOEFL test results in the giving of information (range r = 0.67-0.74). The female students adhered to interacting in English during group sessions, whereas the male students were more likely to revert to using Arabic in elaborating unclear phenomena (p < 0.01). The educational level of the student's mother was highly predictive of TOEFL scores for the male students, but not for female students. Multivariate analysis was undertaken to analyse the relative contribution of the TOEFL, parental education and years of studying in English. The best predictor of students' contributions in PBL groups was identified as TOEFL scores. The study demonstrates the importance of facilitating a locally acceptable level of English proficiency prior to admission to the FMHS. However, it also highlights the importance of not focusing only on English proficiency but paying attention to additional factors in facilitating medical students in maximizing benefits from interactions in PBL settings.

Clinical Competence↗
PubMed1998

Analysis of contact mechanics for composite cushion knee joint replacements.

Recent research in the area of cushion form bearings for total joint replacements has primarily used thin, soft, elastomeric layers with similar elastic modulus to articular cartilage, bonded to rigid substrates. These are designed to promote the body's natural lubricants to separate the articulating surfaces and prevent wear. Applications to joint replacements have revealed that the abrupt change in stiffness between the soft layer and the rigid substrate and the relatively low strength of the interface resulted in high shear stresses and debonding of the soft layer from the substrate. The approach adopted in this study is to use components with a graded modulus or composite construction. The composite construction consists of a soft compliant layer of polyurethane and a second stiffer polyurethane layer thought to be rigid enough to mechanically interlock to a metallic tibial tray. In this composite structure the deformation of the more rigid polyurethane underlay may generally influence the stress distribution and deformation in the softer upper layer and at the interface between the two materials. A simple analysis technique is presented in the present study where the composite double layer was approximated as an equivalent modulus single layer. Single layer theory, which is readily available in the literature, can then be used to determine the contact parameters, including the maximum contact pressure and the contact radius, for the composite structure. By varying the layer thicknesses and material properties of both the soft surface layer and the stiffer structural support layer, the magnitudes and locations of stresses can be controlled. Results of a parametric stress analysis are presented to assist in the selection of the most appropriate composite layers for cushion knee designs. A 4 mm thick surface layer with an elastic modulus of 20 MPa and a 4 mm thick structural support layer with an elastic modulus of 1000 MPa were considered suitable for this application.

Biomechanical Phenomena↗
PubMed1997

Burst activity of ventral tegmental dopamine neurons is elicited by sensory stimuli in the awake cat.

In light of evidence implicating dopamine in the pathophysiology of attention deficit disorder and schizophrenia, diseases involving attentional or sensory processing abnormalities, it was of interest to determine whether and how dopamine neurons in the ventral tegmental area respond to sensory stimuli. The single-unit responses of ventral tegmental dopamine neurons were recorded in freely-moving cats during the presentation of brief, non-conditioned auditory and visual stimuli. Both auditory and visual stimuli produced neuronal excitation, involving a greater than 5-fold increase in the probability of burst firing followed by a period of burst inhibition. The burst nature of the single-unit response suggests that sensory-induced dopamine release at target sites was disproportionally large relative to the discharge frequency. While characteristics of the dopaminergic sensory response were similar for auditory and visual stimuli, the response latency was longer for visual stimuli. The results demonstrate that dopamine neurons in the ventral tegmental area, the site of origin for mesolimbocortical dopamine neurons, are reliably activated by non-conditioned auditory and visual stimuli.

Acoustic Stimulation↗
PubMed1997

Exposure to hepatitis A virus among blood donors, injecting drug users and prison entrants in Victoria.

To assess prevalence of exposure to hepatitis A virus (HAV) among injecting drug users (IDUs) and prison entrants in Victoria, and to compare this with prevalence of HAV among a reference population of blood donors, sera stored from two previous studies and from randomly selected blood donors were tested for total antibody to HAV. The first study was a longitudinal study of field-recruited IDUs from 1990 to 1992 and the second was a study of all prison entrants in 1991-92 (both studies were carried out in Victoria); blood donors were from the Australian Red Cross Blood Bank Victoria in 1995. Forty-five per cent of 2175 prison entrants and 51% of 293 IDUs were seropositive for HAV, compared with 30% of 2995 blood donors. When standardized for age against the blood donors, HAV seropositivity in IDUs was 44% and in prison entrants 60%. The strongest association of HAV seropositivity among the IDUs on multivariate analysis was a history of imprisonment. There are high rates of exposure to HAV among prison entrants, whether with a history of IDU or not, and among IDUs who have a prison history. The role of sharing contaminated injecting equipment in transmission of HAV seems to be less important than institutionalization per se. With adequate resourcing, both populations are appropriate targets for HAV vaccination, especially in a context of continuing decline of transmission of HAV in the general community.

Adolescent↗
PubMed1997

Friction of composite cushion bearings for total knee joint replacements under adverse lubrication conditions.

Conventional joint replacements consist of a polished metallic or ceramic component articulating against a layer of polyethylene. Although the friction in the contact between these articulating surfaces is low, polyethylene wear is produced as a result of a boundary/mixed lubrication regime. Wear debris is generated by direct asperity contact, abrasion, adhesion and fatigue, and has been shown to cause adverse tissue reactions which can lead to joint failure. The introduction of soft compliant materials, similar in stiffness to articular cartilage, has shown that with cyclic loading and relative motion between the articulating surfaces typical of normal walking, a fluid film can be maintained through combined entraining and squeeze-film actions, and hence wear can be minimized. For 95 per cent of the time, however, we are not walking but standing still or moving slowly. A pendulum simulator has been used in the present study to investigate the effect of adverse tribological conditions which may lead to fluid film breakdown, such as severe cyclic loading, particularly in the swing phase, reduced sliding velocity, reduced stroke length and start-up after a period of constant loading. Friction of a model composite cushion knee bearing, manufactured from a graded modulus (20-1000 MPa) layer of polyurethane, sliding against a polished metal cylinder has been measured for various lubricants and the results have been analysed using a Stribeck assessment. Severe cyclic loading, decreased sliding velocity and decreased stroke length have been found to limit the degree of fluid entrainment previously allowed during the swing phase of normal walking, thus allowing breakdown of fluid films and elevated levels of friction and surface damage. Soft layer joint replacements must therefore be designed to operate with thick elastohydrodynamic fluid films to provide some degree of protection when tribological conditions become severe, or alternatively incorporate alternative boundary or mixed lubrication mechanisms. This study quantifies a potential limitation of the cushion bearing concept.

Elasticity↗
PubMed1997

Why do older workers have problems with technology?

Why do older workers seem to have problems with technology? In this paper, I will review several possible reasons and illustrate them with evidence, often anecdotal, from our work as ergonomics practitioners. We find that older workers have more to "unlearn" from their accumulated experience. They may suffer from gradual or not so gradual ailing faculties of sight, hearing, dexterity, stamina, memory, and reaction time. They may exhibit a fear of making mistakes, and they may have strongly established preferences and pessimism about technological gimmicks. But the real problem is often that the designers have failed to anticipate the requirements of their users; they have failed to design for a range of abilities broader than their own; they have failed to test their designs with real people; and they have failed to learn from the experience of the market. Getting design right for older users is really only a continuation of getting design right for all.

Activities of Daily Living↗
PubMed1997

Reduced incidence of rectal cancer, compared to gastric and colonic cancer, in a population of 73,076 men and women chronically immunosuppressed.

The incidence of gastric, colonic, and rectal cancers was determined in a cohort of 73,076 men and women chronically immunosuppressed after heart or renal transplantation, to test the hypothesis that there would be a reduced incidence of gastric cancer by dampening chronic gastritis secondary to infection caused by Helicobacter pylori. Follow-up was from 1-13 years. No change in the incidence of gastric cancer was found (32 cases observed, 32.86 expected). An increase in colon cancer was found (75 cases observed, 62.27 expected). A significant reduction in the incidence of rectal cancer was found (15 cases observed, 41.5 expected). This led to a chi2 of 16.92 with 1 degree of freedom, significant at the 0.1% level. The effect was greater in men than women and more marked in heart recipients than in those receiving renal transplants. This unexpected finding led to a review of experiments in mice and rats that present evidence for immune promotion of large-bowel cancers induced by carcinogens by gut-associated lymphoid tissue. We conclude that an analysis of immune function in gut-associated lymphoid tissue in the stomach, colon, and rectum in healthy and immunosuppressed patients may lead to a better understanding of immunosurveillance in the colon and immune promotion of rectal cancers.

Animals↗
PubMed1996

A further application of the Fishbein and Ajzen model to therapy for adult stammerers.

This paper attempts to address the continuing problem of long term maintenance of fluency-controlling techniques in adults who stammer by applying a number of aspects of the Fishbein and Ajzen model of belief, attitude, intention and behaviour. A group of 15 adult stammerers involved in group therapy were monitored, in terms of speech and attitude change, throughout the programme and followed up two years later. Links between successful maintenance of a fluency-enhancing technique and change in stammerers' attitudes to fluent speech are made.

Adolescent↗
PubMed1996

Acquired stammering in Great Britain.

There are a growing number of reports of late onset of stammering from clinicians but a lack of data concerning the nature, aetiology and outcomes of therapy. This research attempts to replicate in Great Britain a survey of clinicians carried out in America. Clinicians completed a questionnaire on their clients with acquired stammering. Details on possible cause, speech and language characteristics, and therapeutic outcomes were compared with the American study. Results were similar in terms of aetiology and outcome measures despite reported differences in characteristics and treatment regimes offered.

Adolescent↗