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Biomedical subjects

A Moss

Publications and source records attributed to A Moss.

At least 19 recordsLinked to original sources
PubMed2006

Net1 and Myeov: computationally identified mediators of gastric cancer.

Gastric adenocarcinoma (GA) is a significant cause of mortality worldwide. The molecular mechanisms of GA remain poorly characterised. Our aim was to characterise the functional activity of the computationally identified genes, NET 1 and MYEOV in GA. Digital Differential Display was used to identify genes altered expression in GA-derived EST libraries. mRNA levels of a subset of genes were quantitated by qPCR in a panel of cell lines and tumour tissue. The effect of pro- and anti-inflammatory stimuli on gene expression was investigated. Cell proliferation and invasion were measured using in an in-vitro GA model following inhibition of expression using siRNA. In all, 23 genes not previously reported in association with GA were identified. Two genes, Net1 and Myeov, were selected for further analysis and increased expression was detected in GA tissue compared to paired normal tissue using quantitative PCR. siRNA-mediated downregulation of Net1 and Myeov resulted in decreased proliferation and invasion of gastric cancer cells in vitro. These functional studies highlight a putative role for NET1 and Myeov in the development and progression of gastric cancer. These genes may provide important targets for intervention in GA, evidenced by their role in promoting invasion and proliferation, key phenotypic hallmarks of cancer cells.

Adenocarcinoma↗
PubMed2006

The price of adherence: qualitative findings from HIV positive individuals purchasing fixed-dose combination generic HIV antiretroviral therapy in Kampala, Uganda.

Contrary to early expectations, recent studies have shown near-perfect adherence to HIV antiretrovirals in sub-Saharan Africa We conducted qualitative interviews with patients purchasing low-cost, generic antiretroviral therapy to better understand the social dynamics underlying these findings. We found that concerns for family well-being motivate adherence, yet, the financial sacrifices necessary to secure therapy may paradoxically undermine family welfare. We suggest that missed doses may be more due to a failure to access medication rather than a failure to adhere to medications, and that structural rather than behavioral interventions may be most useful to insure optimal treatment response.

Adult↗
PubMed2005

Activation of p38 and p42/44 MAP kinase in neuropathic pain: involvement of VPAC2 and NK2 receptors and mediation by spinal glia.

Activation of intracellular signaling pathways involving p38 and p42/44 MAP kinases may contribute importantly to synaptic plasticity underlying spinal neuronal sensitization. Inhibitors of p38 or p42/44 pathways moderately attenuated responses of dorsal horn neurons evoked by mustard oil but not brush and alleviated the behavioral reflex sensitization seen following nerve injury. Activation of p38 and p42/44 MAP kinases in spinal cord ipsilateral to constriction injury was reduced by antagonists of NMDA, VPAC2 and NK2 (but not related) receptors, the glial inhibitor propentofylline and inhibitors of TNF-alpha. A VPAC2 receptor agonist enhanced p38 phosphorylation and caused behavioral reflex sensitization in naïve animals that could be blocked by co-administration of p38 inhibitor. Conversely, an NK2 receptor agonist activated p42/44 and caused behavioral sensitization that could be prevented by co-administration of p42/44 inhibitor. Thus, spinal p38 and p42/44 MAP kinases are activated in neuropathic pain states by mechanisms involving VPAC2, NK2, NMDA receptors and glial cytokine production.

Animals↗
PubMed2005

Steroid avoidance immunosuppression in low-risk kidney transplant recipients.

Recent clinical trials have documented the short-term safety of steroid avoidance (SA) in kidney transplant recipients. Since July 2003, we have used a SA immunosuppression protocol for low-risk kidney transplant recipients. Eligibility criteria are age > or = 18, primary transplant (living or deceased donor), and tacrolimus started by postoperative day 3. Recipients were excluded if peak/current PRA was >50%/20%, or if they had a positive flow crossmatch, or if they had the recent use of corticosteroids (<6 months). All recipients received induction with rabbit anti-thymocyte globulin, total dose 6 mg/kg, or basiliximab. Recipients received 5 daily doses of corticosteroid and mycophenolate mofetil 1 gm twice daily starting on the day of transplantation. Tacrolimus was started when the serum creatinine level decreased by 20%, or by postoperative day 3. The goal for trough tacrolimus levels was 10-15 ng/mL for the first month, 8-12 ng/mL for months 2-3, and 5-10 ng/mL after month 3. Protocol biopsies (bx) were performed at reperfusion, 1 month, 4 months, and 12 months. Ninety-four kidney transplantations were performed during the study period. Sixty-seven recipients (71%) were eligible and enrolled in SA. Characteristics of the 67 SA recipients: mean age, 53 years (range, 26-70); 41% female; 67% Caucasian; 24% Hispanic; 15% African American; and 5% Native American. Also, 77% received a living donor kidney. The mean follow-up was 180 days (range, 10-360). At last follow-up, 91% remained steroid-free. Biopsy-proven acute rejection (BPAR) occurred in 5 recipients (7.5%). Three recipients (4.5%) had clinical BPAR and 2 had subclinical. One recipient died with pneumonia 4 months following transplantation. Posttransplantation diabetes mellitus (PTDM) occurred in 2 (5%) of 38 recipients. In the initial 41 recipients, 27 had protocol bx at 1 month and 13 at 4 months available for analysis. Chronic allograft nephropathy (CAN) was present on protocol bx in 48% at 1 month and 69% at 4 month. Actuarial (Kaplan-Meier method) patient and graft survival rates at 351 days were 97.8% and 96.8%, respectively. SA with anti-thymocyte globulin induction in low-immunologic risk kidney transplant recipients is safe and is associated with a low risk of BPAR. The incidence of PTDM appears to be lower.

Adrenal Cortex Hormones↗
PubMed2004

Water quality condition and trend in North Queensland waterways.

The Queensland Environmental Protection Agency monitored water quality at 133 sites in North Queensland waterways between Cooktown and Bundaburg from 1992 to 2001. Condition of the waterways was rated by comparing recent data with the Queensland Water Quality Guidelines. Long-term trends were analysed using a censored regression technique that incorporates the effects of flow, temperature, seasonality and allows for long-term non-linear trends. Many sites were in good condition; those in poor condition were usually impacted by point source discharges; those in moderate condition were usually impacted by agricultural land use. There were no consistent long-term trends across the whole region. Recommendations for future programs include incorporating pressure indicators, ensuring high standards of quality assurance, including covariates such as rainfall in trend assessment and continuing programs over more than 10 years to allow detection of trends due to changes in land-use.

Agriculture↗
PubMed2004

Radiation peak skin dose to risk stratify electrophysiological procedures for deterministic skin damage.

UNLABELLED: Ionising radiation is has the potential to cause harm both by increasing the probability future malignancy (stochastic mechanisms) and by direct physical injury (deterministic mechanisms). Several measures have been developed to quantify radiation exposure during a procedure and cardiologists usually refer to fluoroscopic screening time (FST). FST, however, has limitations for predicting deterministic injury which is directly dependant on peak skin dose (PSD). We compared FST to PSD for a range of interventional cardiac electrophysiology procedures. METHODS: All patients undergoing electrophysiology procedures during a 2-month period in our institution were studied. Demographic details, nature of procedure, FST and PSD were measured. The FST to PSD ratio was calculated and compared between patient and procedural factors. RESULTS: 67 procedures on patients (23 female) with body mass index (BMI) of 28 (SD 5) Kg/m2 were studied. Screening times ranged from 0.2 to 96.6 min (median 11.2). PSD ranged from <0.1 to 1108 mGy (median 141). There was a positive correlation between PSD to FST ratio and BMI (r = 0.59, p < 0.001). The PSD to FST ratio was higher in cardiac resynchronization therapy (CRT) devices than single or dual chamber ICDs (p = 0.002). CONCLUSION: FST is not a reliable predictor of deterministic skin injury and in high-risk procedures such as CRT devices and those on individuals of high BMI PSD should be measured.

Body Mass Index↗
PubMed2003

Risk of prevalent HIV infection associated with incarceration among injecting drug users in Bangkok, Thailand: case-control study.

OBJECTIVES: To identify risks for HIV infection related to incarceration among injecting drug users in Bangkok, Thailand. DESIGN: Case-control study of sexual and parenteral exposures occurring before, during, and after the most recent incarceration. SETTING: Metropolitan Bangkok. PARTICIPANTS: Non-prison based injecting drug users formerly incarcerated for at least six months in the previous five years, with documented HIV serostatus since their most recent release; 175 HIV positive cases and 172 HIV negative controls from methadone clinics. MAIN OUTCOME MEASURE: Injection of heroin and methamphetamine, sharing of needles, sexual behaviour, and tattooing before, during, and after incarceration. RESULTS: In the month before incarceration cases were more likely than controls to have injected methamphetamine and to have borrowed needles. More cases than controls reported using drugs (60% v 45%; P=0.005) and sharing needles (50% v 31%; P<0.01) in the holding cell before incarceration. Independent risk factors for prevalent HIV infection included injection of methamphetamine before detention (adjusted odds ratio 3.3, 95% confidence interval 1.01 to 10.7), sharing needles in the holding cell (1.9, 1.2 to 3.0), being tattooed while in prison (2.1, 1.3 to 3.4), and borrowing needles after release (2.5, 1.3 to 4.4). CONCLUSIONS: Injecting drug users in Bangkok are at significantly increased risk of HIV infection through sharing needles with multiple partners while in holding cells before incarceration. The time spent in holding cells is an important opportunity to provide risk reduction counselling and intervention to reduce the incidence of HIV.

Adult↗
PubMed2003

Neuropsychometric outcome following aortic arch surgery: a prospective randomized trial of retrograde cerebral perfusion.

BACKGROUND: Aortic surgery requiring hypothermic circulatory arrest is associated with a high incidence of brain injury. However, knowledge of neuropsychometric outcome is limited. Retrograde cerebral perfusion has become a popular adjunctive technique to hypothermic circulatory arrest. The aim of this study was to assess neuropsychometric outcome and compare the 2 techniques. METHODS: In a prospective randomized trial, 38 patients requiring elective aortic arch surgery were allocated to either hypothermic circulatory arrest plus retrograde cerebral perfusion or hypothermic circulatory arrest alone. Neuropsychometric testing was performed preoperatively, and at 6 weeks and 12 to 24 weeks postoperatively. Deficit was defined as a 20% decline in 2 tests or more. Standardized Z scores were calculated for each patient and test. Eighteen patients underwent hypothermic circulatory arrest and 20 patients underwent hypothermic circulatory arrest plus retrograde cerebral perfusion. The mean cardiopulmonary bypass, hypothermic circulatory arrest, and retrograde cerebral perfusion durations were 169, 30, and 25 minutes, respectively. RESULTS: There were 2 deaths and 2 neurological deficits. At 6 weeks postoperatively, 77% of the hypothermic circulatory arrest group and 93% of the hypothermic circulatory arrest plus retrograde cerebral perfusion group had a deficit (P =.22). At 12 weeks this was reduced to 55% and 56%, respectively (P =.93). There was a worse total Z test score in the hypothermic circulatory arrest plus retrograde cerebral perfusion group at 12 weeks (P =.05). Neuropsychometric change did not correlate with hypothermic circulatory arrest duration, presence of aortic atheroma, cannulation technique, or procedure. CONCLUSIONS: Hypothermic circulatory arrest plus/minus retrograde cerebral perfusion is associated with a high incidence of neuropsychometric change despite ostensibly normal clinical outcomes and apparently safe arrest duration. Retrograde cerebral perfusion did not improve outcome in this small study.

Adult↗
PubMed2001

Provider assessment of adherence to HIV antiretroviral therapy.

BACKGROUND: Adherence assessment is an essential component of monitoring HIV antiretroviral therapy. Prior studies suggest that medical providers frequently estimate individual patient adherence inaccurately. OBJECTIVE: We compared provider estimates of nonadherence to antiretroviral therapy with unannounced pill counts and structured patient interviews to determine the accuracy of adherence information obtained by providers and patients. DESIGN, SETTING, AND PARTICIPANTS: Comparison of three adherence measures in homeless or marginally housed persons receiving HIV antiretroviral therapy (n = 45) and their providers (n = 35). MEASUREMENTS: Provider estimate of percentage of pills taken; three successive patient structured reports of number of doses missed in the last 3 days; and three successive unannounced pill counts. RESULTS: 13% (95% confidence interval [CI], 4%-22%) of patients were not following their regimen as directed. Provider-adherence estimate explained only 26% (95% CI, 6%-47%) of the variation in pill count adherence, whereas patient report explained 72% (95% CI, 52%-96%). The sensitivity and specificity of provider estimates of nonadherence, defined as <80% of pills taken by pill count, were 40% and 85%, respectively. The sensitivity and specificity of patient interview were 72% and 95%, respectively. CONCLUSIONS: Provider estimate of adherence was inaccurate whereas structured patient report was more closely related to pill count. Structured assessment over several short intervals may improve accuracy of adherence assessment in clinical practice.

Antiretroviral Therapy, Highly Active↗
PubMed2001

Fanconi anemia proteins localize to chromatin and the nuclear matrix in a DNA damage- and cell cycle-regulated manner.

Fanconi anemia (FA) is a genetic disease characterized by congenital defects, bone marrow failure, and cancer susceptibility. Cells from patients with FA exhibit genomic instability and hypersensitivity to DNA cross linking agents such as mitomycin C. Despite the identification of seven complementation groups and the cloning of six genes, the function of the encoded gene products remains elusive. The FancA (Fanconi anemia complementation group A), FancC, and FancG proteins have been detected within a nuclear complex, but no change in level, binding, or localization has been reported as a result of drug treatment or cell cycle. We show that in immunofluorescence studies, FancA appears as a non-nucleolar nuclear protein that is excluded from condensed, mitotic chromosomes. Biochemical fractionation reveals that the FA proteins are found in nuclear matrix and chromatin and that treatment with mitomycin C results in increase of the FA proteins in nuclear matrix and chromatin fractions. This induction occurs in wild-type cells and mutant FA-D (Fanconi complementation group D) cells but not in mutant FA-A cells. Immunoprecipitation of FancA protein in chromatin demonstrates the coprecipitation of FancA, FancC, and FancG, showing that the FA proteins move together as a complex. Also, fractionation of mitotic cells confirms the lack of FA proteins in chromatin or the nuclear matrix. Furthermore, phosphorylation of FancG was found to be temporally correlated with exit of the FA complex from chromosomes at mitosis. Taken together, these findings suggest a role for FA proteins in chromatin and nuclear matrix.

Cell Cycle↗
PubMed2001

Cooperation, control, and concession in meerkat groups.

"Limited control" models of reproductive skew in cooperative societies suggest that the frequency of breeding by subordinates is determined by the outcome of power struggles with dominants. In contrast, "optimal skew" models suggest that dominants have full control of subordinate reproduction and allow subordinates to breed only when this serves to retain subordinates' assistance with rearing dominants' own litters. The results of our 7-year field study of cooperative meerkats, Suricata suricatta, support the predictions of limited control models and provide no indication that dominant females grant reproductive concessions to subordinates to retain their assistance with future breeding attempts.

Africa, Southern↗
PubMed2001

Tubulin stimulates adenylyl cyclase activity in C6 glioma cells by bypassing the beta-adrenergic receptor: a potential mechanism of G protein activation.

While the cytoskeleton is known to play several roles in the biology of the cell, one role, which has been revealed only recently, is that of a participant in the signal transduction process. Tubulin binds specifically to the alpha subunits of Gs (stimulatory GTP-binding regulatory protein of adenylyl cyclase), Gi1 (inhibitory protein of adenylyl cyclase), and Gq and transactivates those molecules through direct transfer of GTP. The relevance of this transactivation process to G proteins which are normally activated by a neurotransmitter-occupied receptor is the subject of this study. C6 glioma cells, made permeable with saponin, retained tight coupling between Gs and the beta-adrenergic receptor. Although 5-guanylylimidodiphosphate (GppNHp) was incapable of activating Gs (and subsequently, adenylyl cyclase) in the absence of agonist, tubulin with GppNHp bound (tubulin-GppNHp) activated adenylyl cyclase with an EC(50) of 30 nM. Desensitization of beta-adrenergic receptors by isoproterenol exposure had no effect on the ability of tubulin-GppNHp to activate Gs and adenylyl cyclase. When the photoaffinity GTP analog, azidoanilido GTP (AAGTP; P3(4-azidoanilido)-P1-5'-GTP), was added to C6 membranes or permeable C6 cells, it was only weakly incorporated by G alpha s in the absence of isoproterenol. When the same concentration of dimeric tubulin with AAGTP bound was introduced, AAGTP was transferred from tubulin to G alpha s, activating the latter species. Similar 'preferential' activation of G alpha s by tubulin-AAGTP versus the free nucleotide was seen using purified components. Thus, membrane-associated tubulin may serve to activate G alpha s, independent of signals not normally coupled to that protein. Tubulin may act as an agent to link a variety of membrane-associated signalling systems.

Adenylyl Cyclases↗
PubMed2001

Serological survey for Ehrlichia canis in urban dogs from the major population centres of northern Australia.

OBJECTIVE: To detect evidence of Ehrlichia canis infection of dogs from the major population centres of northern Australia, if present. DESIGN: Serological investigation for E. canis. PROCEDURE: The sera of 316 domestic dogs, collected from the northern Australian population centres of Townsville, Cairns, Darwin, Kununurra and Broome from May 1997 to August 1999, were investigated for evidence of infection with E. canis. Samples were tested for antibodies to E. canis using an indirect fluorescent antibody (IFA) test. The buffy coats from blood of dogs whose serum reacted in the IFA test were subsequently tested with a nested PCR to detect E. canis DNA. When available, blood from these dogs was injected into suckling mice, which were then examined for clinical disease and tested for the presence of E. canis antibodies. RESULTS: Of the 316 samples tested seven reacted in the IFA test for E. canis. None of the dogs from which these samples were obtained exhibited clinical signs of acute or chronic ehrlichiosis. The six positive samples available for testing were negative when tested with the nested PCR. Suckling mice inoculated with blood from three of the dogs whose serum was positive by IFA test showed no signs of clinical disease nor did their give positive reactions in the IFA test. CONCLUSIONS: No evidence of E. canis infection was confirmed in any of the dogs examined. Northern Australia would appear to remain free of this obligate parasite.

Animals↗
PubMed2001

From coping with life to coping with death: problematic integration for the seriously ill elderly.

Decisions made by and for elderly patients nearing death frequently perpetuate unwanted suffering and dependence. This article extends the argument that Babrow's (1992, 1995) problematic integration theory can provide insights into why communication fails to produce desired outcomes for such patients. Open-ended responses obtained in face-to-face interviews with 142 elderly dialysis patients and mailed surveys of 393 dialysis unit nurses were examined to better understand how patients and nurses reconciled incompatible probabilistic and evaluativejudgments. Results indicate that patients seek information that will enable them to cope with debilitating dialysis treatments rather than information nurses believe is necessary for them to make informed choices about whether to undergo such treatments. The tension between the information patients want to successfully cope with life and the information they need to decide intelligently about treatments that forestall death constitutes a key reason why communication about end-of-life issues is frequently flawed. Our analysis of these communication flaws leads to specific recommendations for how this tension can be eased, which in turn may better prepare patients to make the transition from coping with life to coping with death.

Adaptation, Psychological↗