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Biomedical subjects

J G Walker

Publications and source records attributed to J G Walker.

At least 19 recordsLinked to original sources
PubMed2007

Characterisation of a dendritic cell subset in synovial tissue which strongly expresses Jak/STAT transcription factors from patients with rheumatoid arthritis.

OBJECTIVES: To characterise the phenotype of the putative dendritic cells strongly expressing Jak3 and STAT4, which have been previously identified in the synovial tissue of patients with active rheumatoid arthritis (RA). METHODS: Synovial biopsy specimens were obtained at arthroscopy from 30 patients with active RA (42 synovial biopsies). Immunohistological analysis was performed using monoclonal antibodies to detect dendritic cell subsets, including activation markers and cytokines relevant to dendritic cell function. Co-localisation of cell surface markers and cytokines was assessed primarily using sequential sections, with results confirmed by dual immunohistochemistry and immunofluorescence with confocal microscopy. RESULTS: The dendritic cells identified in RA synovial tissue that strongly express Jak3 also strongly express STAT4 and STAT 6 and are correlated with the presence of serum rheumatoid factor. These cells are not confined to a single dendritic cell subset, with cells having phenotypes consistent with both myeloid- and plasmacytoid-type dendritic cells. The activation status of these dendritic cells suggests that they are maturing or mature dendritic cells. These dendritic cells produce IL12 as well as interferon alpha and gamma. CONCLUSIONS: The close correlation of these dendritic cells with the presence of serum rheumatoid factor, a prognostic factor for worse disease outcome, and the strong expression by these cells of components of the Jak/STAT transcription factor pathway suggest a potential therapeutic target for the treatment of RA.

Adult↗
PubMed2006

Changes in synovial tissue Jak-STAT expression in rheumatoid arthritis in response to successful DMARD treatment.

BACKGROUND: Modulation of Jak-STAT signalling may provide an effective therapeutic strategy in inflammatory arthritis (IA). OBJECTIVE: To examine the effect of successful disease-modifying antirheumatic drug (DMARD) treatment on the expression of Jak-STAT in a cohort of patients with active rheumatoid arthritis. METHODS: Synovial tissue biopsy specimens from 16 patients with active rheumatoid arthritis, taken before and after initiation of DMARD treatment, were examined for the presence of janus kinase (Jak)3, signal transducer and activator of transcription (STAT)1, STAT4 and STAT6 expression using immunohistochemistry. RESULTS: Successful treatment with DMARDs results in reduction in STAT1 expression in the lining, and STAT1 and STAT6 in the sublining of rheumatoid arthritis synovial tissue. Although the overall expression of STAT4 and Jak3 was not significantly altered by DMARD treatment, there was a significant reduction in the expression of the STAT4 and Jak3 bright cells, thought to be an activated dendritic cell subpopulation. CONCLUSION: Results show that Jak3, STAT1, STAT4 expression and STAT6 sublining expression decrease in response to successful treatment of rheumatoid arthritis with standard DMARDs. Therefore, altering the expression of these pathways may represent an alternative treatment option, either through promoting up-regulation of inhibitory pathways, or suppressing inflammatory paths.

Antirheumatic Agents↗
PubMed2006

Scleroderma in South Australia: further epidemiological observations supporting a stochastic explanation.

The aim of this study was to determine the incidence, prevalence, survival and selective demographic characteristics of scleroderma occurring in South Australia over the 10-year period 1993-2002. Analysis of the database of the South Australian Scleroderma Register: a population-based register established in 1993. Patients with scleroderma resident in South Australia (n = 353 at 2002) were ascertained from multiple sources and clinical and demographic data were obtained from mailed questionnaire and from review of computerized hospital databases, case notes or referring letters. Time-space cluster analysis was carried out according to the Knox method. Control data were obtained from the Australian Bureau of Statistics census. The mean prevalence was 21.4 per 10(5) (95% confidence interval 20.2-22.6) and the mean cumulative incidence of 1.5 per 10(5) (95% confidence interval 1.32-1.73) with no significant change in incidence over the study period (P = 0.13). Cumulative survival improved over the study period, with patients with diffuse disease having significantly reduced survival (as compared with limited disease, P < 0.001). The proportion with diffuse disease ( approximately 22%) remained steady. There was a small but significant predisposition in patients with a continental European birthplace (P < 0.001). A family history of scleroderma was noted in 1.6% with lambda1 (familial risk) of 14.3 (95% confidence interval 5.9-34.5). However, a family history of systemic autoimmunity (especially rheumatoid arthritis) was more common (6%). No socioeconomic stratification, temporal clustering nor spatio-temporal clustering was observed either at time of initial symptom or at 10 years before disease onset. Scleroderma occurs relatively infrequently in South Australia with no significant change in incidence observed over the 10-year study period. However, cumulative survival has improved. Identified risk factors include family history of scleroderma (risk approximately 14-fold), female sex (risk approximately 5-fold) and European birthplace (risk approximately 2.5-fold); however, the majority of the disease variance appears unexplained. A stochastic explanation based on genetic instability is favoured to explain this paradox.

Female↗
PubMed2006

Scleroderma: it has been a long hard journey.

Progress in the understanding of the aetiopathogenesis of scleroderma (systemic sclerosis) has been painfully slow and this has greatly impeded the application of specific disease modifying treatments. This article provides a brief historical overview of scleroderma (including the important Australian contribution of Dr Alfred Barnett and colleagues--see accompanying article in this issue on pages 513-18), highlights some recent pathogenic developments and summarises some exciting new therapies. Cautious optimism can now be offered to scleroderma sufferers.

Animals↗
PubMed2006

Psychological distress and visual functioning in relation to vision-related disability in older individuals with cataracts.

OBJECTIVE: To determine whether demographic, health status and psychological functioning measures, in addition to impaired visual acuity, are related to vision-related disability. METHODS: Participants were 105 individuals (mean age=73.7 years) with cataracts requiring surgery and corrected visual acuity in the better eye of 6/24 to 6/36 were recruited from waiting lists at three public out-patient ophthalmology clinics. Visual disability was measured with the Visual Functioning-14 survey. Visual acuity was assessed using better and worse eye logMAR scores and the Melbourne Edge Test (MET) for edge contrast sensitivity. Data relating to demographic information, depression, anxiety and stress, health care and medication use and numbers of co-morbid conditions were obtained. RESULTS: Principal component analysis revealed four meaningful factors that accounted for 75% of the variance in visual disability: recreational activities, reading and fine work, activities of daily living and driving behaviour. Multiple regression analyses determined that visual acuity variables were the only significant predictors of overall vision-related functioning and difficulties with reading and fine work. For the remaining visual disability domains, non-visual factors were also significant predictors. Difficulties with recreational activities were predicted by stress, as well as worse eye visual acuity, and difficulties with activities of daily living were associated with self-reported health status, age and depression as well as MET contrast scores. Driving behaviour was associated with sex (with fewer women driving), depression, anxiety and stress scores, and MET contrast scores. CONCLUSION: Vision-related disability is common in older individuals with cataracts. In addition to visual acuity, demographic, psychological and health status factors influence the severity of vision-related disability, affecting recreational activities, activities of daily living and driving.

Activities of Daily Living↗
PubMed2005

Expression of Jak3, STAT1, STAT4, and STAT6 in inflammatory arthritis: unique Jak3 and STAT4 expression in dendritic cells in seropositive rheumatoid arthritis.

BACKGROUND: Modulation of Jak-STAT signalling may provide an effective therapeutic strategy in inflammatory arthritis. OBJECTIVE: To document Jak-STAT expression in a cohort of patients with active rheumatoid arthritis (RA), spondyloarthritis (SpA), and osteoarthritis (OA) and compare these subsets with normal synovial tissue. METHODS: Synovial tissue biopsy specimens from patients with RA, OA, and SpA and histologically normal tissue (n = 10 in each arthritis group) were examined for the presence of Jak3, STAT1, STAT4, and STAT6 expression using immunohistochemistry. Phenotyping was performed using immunohistochemistry and immunofluorescence. Clinical and serological characteristics of patients with RA expressing Jak3-STAT4 were assessed. RESULTS: STAT1, STAT4, and Jak3 protein expression was generally increased in inflammatory arthritis. In contrast, STAT6 expression was relatively heterogeneous. A subpopulation of CD1a positive dendritic cells unique to seropositive patients with RA was detected. These cells showed intense protein expression for Jak3, STAT4, and STAT6. CONCLUSION: CD1a positive dendritic cells intensely express Jak3, STAT4, and STAT6 in seropositive RA tissue and may be an alternative marker for dendritic cells in their early stages of activation as well as providing a tool for identifying RA at the level of the synovium. Jak3 inhibition may be a potential therapeutic target to prevent dendritic cell maturation in RA. STAT1 expression is increased in inflammatory arthritis, suggesting that its pro-apoptotic and anti-inflammatory effects cannot effectively counteract inflammation. STAT6 expression is heterogeneous in synovium, suggesting a possible homoeostatic role in addition to any anti-inflammatory effects.

Adult↗
PubMed2005

Isolated pulmonary hypertension in scleroderma.

BACKGROUND: Isolated pulmonary hypertension (PHT) is now the most frequent cause of disease-related death in limited cutaneous scleroderma, the commonest disease variant of this disabling connective tissue disorder. Endothelin-1 receptor antagonists provide symptomatic benefit but to date have not been shown to prolong survival. AIM: To determine the frequency, disease characteristics and survival of symptomatic patients with isolated PHT in our cohort of scleroderma patients. METHODS: Systematic review of the clinical course of all patients registered on the South Australian Scleroderma Register, a population-based register of 374 living and 234 deceased patients with scleroderma. RESULTS: Thirty-four patients were identified with isolated PHT, the majority with limited scleroderma. From our deceased register, we estimate that >11% of patients with this limited variant will develop this complication. Isolated PHT occurs as a late-stage complication approximately 20 years after the first symptoms of scleroderma. Patients with isolated PHT were characterized by the presence of multiple telangiectasia, reduced nailfold capillary density, digital ulceration, gross reduction of diffusing capacity for carbon monoxide and echocardiographic evidence of elevated pulmonary artery pressure. Survival was significantly shortened as compared with those patients without this complication (P=0.002), with a mean survival of 2.5 years from symptomatic onset of PHT. CONCLUSION: Isolated PHT occurs as a late-stage complication in > or =11% of patients with limited cutaneous scleroderma and leads to rapid death from right heart failure. The early use of endothelin-1 receptor antagonists may change the natural history of this fatal complication.

Aged↗
PubMed2005

Scleroderma in Australian aborigines.

Scleroderma (systemic sclerosis) has not been reported before in Australian Aborigines. We describe in detail a community middle-aged Aboriginal woman whose diffuse scleroderma terminated fatally with a renal crisis. Moreover, we have identified a further five Aboriginal patients on the South Australian Scleroderma Register (two with diffuse, two with limited and one with overlap scleroderma), a number consistent with that expected from the 2001 census data for our state. However, an analysis of all antinuclear antibody (ANA) requests from the Top End of Australia over a 6-year period revealed only two Aborigines with low titre anticentromere antibody (despite frequent occurrence of ANA with other specificities). Neither of these Aborigines had features of scleroderma. In conclusion, scleroderma does occur in indigenous Australians but further studies are needed to confirm the apparent infrequency of centromere-associated limited scleroderma (which is the commonest form of scleroderma in our Caucasian population).

Antibodies, Antinuclear↗
PubMed2002

Analysis of the spatial distribution of polarized light backscattered from layered scattering media.

The scattering of polarized light from a two layer scattering medium is investigated using Monte Carlo simulations. First order and normalized second order moments are used to analyze the spatial properties of the emerging light in different polarization states. Linearly and circularly polarized illumination is used to probe different depths. Absorption and layer thickness are varied and it is demonstrated that the determination of these values is aided by the inclusion of polarization information. The lateral and depth localization of light by polarization subtraction is also quantified. Potential applications of these techniques are burn depth and melanoma thickness measurements.

Biophysical Phenomena↗
PubMed2000

Diurnal stability of refraction after implantation with intracorneal ring segments.

PURPOSE: To investigate diurnal changes in visual acuity and refraction in myopic eyes implanted with intracorneal ring segments (ICRS). SETTING: University of California San Diego Shiley Eye Center, La Jolla, California, and Emory University Vision Correction Center, Atlanta, Georgia, USA. METHODS: This prospective study involved 2 groups of patients who had ICRS (Intacs) implantation and a follow-up of at least 6 months. The first group included 102 eyes of 51 bilaterally treated patients; the second group, 32 eyes of 16 unilaterally treated patients. Examinations including visual acuity, manifest refraction, and videokeratography were done in the morning and evening at least 9 hours apart on a single day. Refractive changes were analyzed by power vectors; multivariate statistics were used to determine the significance of change in any component of the spectacle prescription. RESULTS: In the bilateral treatment group, 97 eyes (95%) were within 1 line of spectacle-corrected visual acuity from morning to evening. The mean change in manifest refraction was -0.14 +0.08 x 4 and in spherical equivalent, -0.10 diopters (D) (sigma = 0.3; range -0.750 to +0.875 D). Ninety-six eyes (94%) had a change in refraction within 0.50 D of spherical equivalent. There was no significant change in corneal power (P =.20). In the unilateral treatment group, there was no significant difference between treated and untreated eyes in changes in spectacle-corrected visual acuity, manifest refraction, or corneal power and toricity (P.05). CONCLUSION: No clinically significant diurnal variation in visual acuity or manifest refraction was observed after ICRS implantation or in untreated paired eyes. Moreover, the data suggest less diurnal change in visual acuity and refraction after ICRS implantation.

Circadian Rhythm↗
PubMed1999

Complications of laser in situ keratomileusis for the correction of myopia.

OBJECTIVE: To determine the incidence and severity of complications from laser in situ keratomileusis (LASIK) for the correction of myopia by experienced and inexperienced surgeons. DESIGN: Prospective, observational clinical study. PARTICIPANTS: Fourteen surgeons and 1062 eyes of 574 myopic patients who desired surgical correction of myopia ranging from -2.00 to -22.50 diopters (D; mean, -7.57 D) and astigmatism no greater than 4.00 D participated in this study. INTERVENTION: Myopia was corrected with LASIK. Astigmatism was corrected with arcuate keratotomy at the same time as the initial procedure or subsequently. MAIN OUTCOME MEASURES: Primary outcome measures were change in best spectacle-corrected visual acuity (BSCVA) and the incidence of complications. RESULTS: Eyes were followed for a mean of 9.5 months after their last surgical procedure (range, 2 weeks-21 months). Three hundred eighty-one eyes (36%) underwent 468 enhancement procedures 3 months or more after the initial treatment. There were 27 (2.1%) intraoperative and 40 (3.1%) postoperative complications. Laser ablation was not performed during the initial treatment of 17 (1.6%) eyes because of intraoperative complications. Seventy-four eyes gained 2 or more lines of BSCVA, while 50 eyes lost 2 or more lines of BSCVA. Only three eyes lost two or more lines of BSCVA to a level worse than 20/40. One eye with a flap buttonhole (BSCVA 20/50) also had an epiretinal membrane. The second eye (BSCVA 20/60) had a flap buttonhole that may have been related to a previous corneal transplant. The third eye (-22.50 D before surgery) had a rhegmatogenous retinal detachment develop, reducing BSCVA from 20/60 to 20/200. The incidence of intraoperative complications decreased from 3.1% during the first 3 months to 0.7% during the last 9 months of the study (P = 0.02). CONCLUSIONS: LASIK is acceptably safe for the correction of myopia. Although complications occur in approximately 5% of cases, these rarely lead to visual loss of more than two Snellen lines and postoperative acuity below 20/40. Flap buttonholes were more likely to cause loss of BSCVA than free or incomplete flaps (P = 0.02); flap buttonholes may be more likely in eyes that have undergone previous surgery. Complication rates can be reduced as the surgical team gains experience.

Astigmatism↗
PubMed1999

Stress system response and rheumatoid arthritis: a multilevel approach.

A growing body of research indicates that the stress system, and its interactions with the immune system, play a pivotal role in the aetiology and progression of rheumatoid arthritis (RA). The stress system has multiple levels and comprises physiological, psychological and environmental components. However, most investigations in RA that involve the stress system tend to focus on the interrelationships between neuroendocrine and immune function, and related disease activity, with little regard for the role of other aspects of stress system activation, including psychological variables. This is despite the fact that psychological stressors, and related psychological variables, are known to influence RA disease activity. This article aims to explore the multiple levels of stress system activation and how they may ultimately influence disease-related outcomes in RA. Some measurement issues of psychological stress will also be examined.

Arthritis, Rheumatoid↗
PubMed1998

Prevalence and distribution of QPX, Quahog Parasite Unknown, in hard clams Mercenaria mercenaria in Virginia, USA.

In July 1996, the Virginia Institute of Marine Science initiated a sampling program to examine wild and cultured hard clams Mercenaria mercenaria for QPX, Quahog Parasite Unknown, a protistan parasite associated with severe mortalities of hard clams in localized areas in maritime Canada and Massachusetts, USA. The sampling program set out to seasonally monitor wild clams from one site, James River, Virginia, and cultured clams from 2 sites, Chincoteague Bay and Mattawoman Creek, Virginia. Histological examination of initial samples revealed 8% prevalence of the parasite in 1-2 yr old cultured clams in Chincoteague Bay. This is the first documentation of QPX in Virginia. To ascertain the distribution of the parasite in Virginia, the survey was expanded between August 1996 and July 1997 to include 16 additional sites. A total of 1305 wild and cultured clams was sampled from Chesapeake Bay tributaries and coastal areas where harvest and culture occur. QPX was not found in Chesapeake Bay, but was present in cultured clams from 3 coastal embayments--the original Chincoteague Bay site, Burton Bay and Quinby Inlet. The parasite was found in Chincoteague Bay at each sample period at prevalences ranging from 8 to 48%. Infections were generally light to moderate intensity and were most often observed in mantle and gill tissues. The maximum prevalence was observed in May 1997 and coincided with notable clam mortalities. QPX prevalences at the other sites were low, ranging from 4 to 15%. To date QPX has not had a significant impact on Virginia's hard clam fishery and aquaculture industry; however, the presence of the pathogen in 3 of the state's most productive hard clam growout areas warrants continued monitoring and research.

Animals↗
PubMed1996

Emotionally focused marital intervention for couples with chronically ill children.

Couples with chronically ill children are at risk for experiencing marital stress. The present study was a randomized control trial that assessed the efficacy of emotionally focused therapy (EFT) in decreasing marital distress in this population of couples. Thirty-two couples with chronically ill children seen at a tertiary care pediatric hospital were randomly assigned to EFT or to a waitlist control group. EFT couples demonstrated significant decreases in marital distress at posttreatment and at a 5-month follow-up in comparison to controls. Clinical improvements in marital functioning following EFT were also demonstrated.

Adaptation, Psychological↗
PubMed1992

Measuring marital distress in couples with chronically ill children: the Dyadic Adjustment Scale.

The idea that couples with chronically ill children are particularly at risk for marital distress has been supported by clinical observation and empirical research. Three recent controlled studies, however, did not find evidence for this increased risk. A possible explanation for the discrepant findings is that these three studies employed Spanier's Dyadic Adjustment Scale (DAS) as a unidimensional measure of marital adjustment. To develop a better understanding of the discrepant findings of risk for marital distress in couples with chronically ill children, the present study examined both the appropriateness of the DAS's published norms as well as the criterion validity of the DAS for use in this population of couples. Three hundred and sixteen parents (158 couples) from a large urban pediatric health care setting completed a survey investigating interest and need to participate in an intervention program for marital distress. Results indicated that this instrument can reliably predict marital distress in this population of couples, however, mean DAS scores are higher than those established by Spanier.

Adaptation, Psychological↗
PubMed1989

Differences in the nature and kinetics of the ethanol-related circulating cytotoxic proteins in normal subjects and patients with alcohol-induced cirrhosis.

The kinetics and nature of the nondialyzable cytotoxic activity which appeared in the serum after the consumption of 1.2 g ethyl alcohol per kilogram body weight over 45 min was studied in six healthy volunteers and eight patients with histologically proven alcohol-related cirrhosis of the liver. Whereas the cytotoxic activity in the dialyzed serum showed a single peak with a maximum value 8 hr after the start of ethanol consumption in the healthy volunteers, it showed two peaks with maximum values at 2 and 8 hr in the patients with cirrhosis. Studies of the fractions obtained by Sephacryl-S-300 gel filtration of the 2-hr postalcohol serum samples revealed substantial cytotoxic activity in the fractions containing both the albumin peak and the IgG peak in the patients with cirrhosis and only in the fractions containing the albumin peak in the healthy volunteers. Experiments with pure IgG preparations obtained from prealcohol and 2-hr postalcohol sera by chromatography on Q-Sepharose Fast Flow anion-exchange resin showed considerable cytotoxic activity in the preparations from the patients with cirrhosis and little or no cytotoxic activity in those from the healthy volunteers. Thus, the early peak of the biphasic serum cytotoxicity curve seen after ethanol consumption by patients with cirrhosis appeared to be caused by the development of a substantial cytotoxic activity in the IgG molecules during the first 2 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaldehyde↗