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L Stokes

Publications and source records attributed to L Stokes.

16 recordsLinked to original sources
PubMed2006

Characterization of a selective and potent antagonist of human P2X(7) receptors, AZ11645373.

BACKGROUND AND PURPOSE: The ATP-gated P2X(7) receptor has been shown to play a role in several inflammatory processes, making it an attractive target for anti-inflammatory drug discovery. We have recently identified a novel set of cyclic imide compounds that inhibited P2X(7) receptor-mediated dye uptake in human macrophage THP-1 cells. In this study the actions and selectivity of one of these compounds, AZ11645373, were characterized. EXPERIMENTAL APPROACH: We measured membrane currents, calcium influx, and YOPRO-1 uptake from HEK cells expressing individual P2X receptors, and YOPRO1 uptake and interleukin-1beta release from THP-1 cells in response to ATP and the ATP analogue benzoylbenzoyl ATP (BzATP). KEY RESULTS: AZ11645373 up to 10 microM, had no agonist or antagonist actions on membrane currents due to P2X receptor activation at human P2X(1), rat P2X(2), human P2X(3), rat P2X(2/3), human P2X(4), or human P2X(5) receptors expressed in HEK cells. AZ11645373 inhibited human P2X(7) receptor responses in HEK cells in a non-surmountable manner with K (B) values ranging from 5 - 20 nM, with mean values not significantly different between assays. K (B) values were not altered by removing extracellular calcium and magnesium. ATP-evoked IL-1beta release from lipopolysaccharide-activated THP-1 cells was inhibited by AZ11645373, IC(50) = 90 nM. AZ11645373 was > 500-fold less effective at inhibiting rat P2X(7) receptor-mediated currents with less than 50% inhibition occurring at 10 microM. CONCLUSIONS AND IMPLICATIONS: AZ11645373 is a highly selective and potent antagonist at human but not rat P2X(7) receptors and will have much practical value in studies of human cells.

Adenosine Triphosphate↗
PubMed2005

Dinitrogen oxide detection for nitrification failure early warning systems.

Experiments were conducted in order to establish whether N2O could be used to predict nitrification failure (through non-invasive means). Previous research had shown a strong correlation between N2O gas and NH3 in the effluent, giving rise to the possibility N2O can be used as an indicator for failure in the nitrification process. Two pilot-scale activated sludge plants were used, each with two lanes. The smaller consisted of a 601 aeration tank and a 201 clarifier; the larger pilot plant had an aeration tank of 3151 and a clarifier of 1001. The small pilot plant experiments showed that N2O gas was given off almost immediately from O2 deprivation/NH3 shock loads, but did not follow the expected trend of the time lag of NH3 in the effluent. This led to further investigation in the hydrodynamics and mixing characteristics of aeration basins, where a second larger pilot plant was used. Further experiments were conducted of high NH3 loadings and O2 deprivation, showed that work of was reproducible. However, it was also shown that with partial nitrification failure, a different N2O response of a continual rise was observed.

Ammonia↗
PubMed2000

109Cd K x ray fluorescence measurements of tibial lead content in young adults exposed to lead in early childhood.

OBJECTIVES: Tibia lead measurements were performed in a population of 19-29 year old people who had been highly exposed to lead in childhood to find whether lead had persisted in the bone matrix until adulthood. METHODS: (109)Cd K x ray fluorescence was used to measure the tibia lead concentrations of 262 exposed subjects and 268 age and sex matched controls. Questionnaire data allowed a years of residence index to be calculated for exposed subjects. A cumulative blood lead index was calculated from the time weighted integration of available data of blood lead. RESULTS: The mean (SEM) difference between exposed and control men was 4.51 (0.35) micrograms Pb/g bone mineral, and between exposed and control women was 3.94 (0. 61) micrograms Pb/g bone mineral. Grouped mean bone lead concentrations of exposed subjects were predicted best by age. When exposed and control subjects' data were combined, grouped mean bone lead concentrations were predicted best by cumulative blood lead index. The years of residence index was neither a good predictor of bone lead concentrations for exposed subjects nor for exposed and control subjects combined. Finally, exposed subjects had increased current blood lead concentrations that correlated significantly with bone lead values. CONCLUSION: Bone lead concentrations of exposed subjects were significantly increased compared with those of control subjects. Lead from exposure in early childhood had persisted in the bone matrix until adulthood. Exposed subjects had increased blood lead concentrations compared with controls. Some of this exposure could be related to ongoing exposure. However, some of the increase in blood lead concentration in adult exposed subjects seemed to be a result of endogenous exposure from increased bone lead stores. The endogenous exposure relation found for men was consistent with reported data, but the relation found for women was significantly lower. Further research is needed to find whether the observed differences are due to sex, or pregnancy and lactation.

Adult↗
PubMed1999

Factors affecting in vivo measurement precision and accuracy of 109Cd K x-ray fluorescence measurements.

109Cd K x-ray fluorescence (XRF) measurement systems from two research centres were used to measure tibia lead content in a population (n = 530) of young adults. The group mean bone lead contents (+/-SEM) determined by McMaster University (n = 214) and the University of Maryland (n = 316) were 2.80 +/- 0.51 and 2.33 +/- 0.50 microg Pb/(g bone mineral) respectively. The mean difference of 0.47 +/- 0.71 microg Pb/(g bone mineral) was not significant. There was no evidence of a systematic difference between measurements from the two systems. Measurement uncertainties for the young adults were poorer overall than uncertainties for a population of occupationally exposed men. This was because obese subjects and women were included in the study. Regressions of precision against body mass index (BMI, defined as weight/height2) determined that uncertainties increased with BMI and were poorer for women than men. Measurement uncertainties (1sigma) were >8 microg Pb/(g bone mineral) for women with a BMI > 0.004 kg cm(-2). Poor-precision data affected population estimates of bone lead content; an inverse correlation was found between precision and bone lead content. A small number (0.4%) of individual measurements with poor uncertainties were inaccurate to within the precision. It is suggested that obese subjects, whose BMI > 0.004 kg cm(-2), should be excluded from 109Cd K XRF studies, as the measurement provides limited information and may be inaccurate.

Adult↗
PubMed1998

Success rate with repeated cycles of in vitro fertilization-embryo transfer.

OBJECTIVE: To analyze data from a large multicenter study to determine whether pregnancy and delivery rates decrease with repeated IVF-ET cycles. DESIGN: Multicenter retrospective study. SETTING: Participating centers from the Society of Assisted Reproductive Technology. PATIENT(S): Fifty-four centers contributed 4,043 cycles of oocyte retrieval for uterine transfer. INTERVENTION(S): Oocyte retrieval for uterine transfer. MAIN OUTCOME MEASURE(S): Pregnancy and delivery rates, analyzed according to age, program success rate, and whether the program was doing assisted hatching. RESULT(S): Pregnancy and delivery rates for cycles 1, 2, 3, 4, and >4 were 33.7% and 27.0%, 33.9% and 27.4%, 28.9% and 23.4%. 25.9% and 16.1%, and 21.0% and 15.4%, respectively. The pregnancy rate decreased significantly for >4 cycle; delivery rate decreased significantly for cycles 4 and >4. Assisted hatching was strongly related to better odds of pregnancy (OR, 1.50) and delivery (OR, 1.44) in women under age 40, and for pregnancy (1.64) in women age 40-42 years. CONCLUSION(S): Success rates do not decrease markedly with repeated IVF attempts, and the decrease did not change with program success rate, suggesting the IVF population is not markedly heterogeneous. Uncontrolled studies of new treatments for cycle repeaters cannot assume that success rate is poor without a treatment change.

Adult↗
PubMed1998

Neurotoxicity in young adults 20 years after childhood exposure to lead: the Bunker Hill experience.

OBJECTIVES: An epidemiological study of young adults was conducted to determine whether environmental exposure to lead during childhood was associated with current adverse neurobehavioural effects. METHODS: The exposed group consisted of 281 young adults who had been exposed environmentally to lead as children and the unexposed referent group consisted of 287 age and sex frequency matched subjects. Information on demographics, past and current health, and past exposures to neurotoxicants, and responses to the Swedish Q16 questionnaire were collected by interview. Standard neurobehavioural and neurophysiological tests were administered by computer or trained technicians. K x ray fluorescence was used to estimate tibial bone lead concentrations among the exposed and unexposed groups. Associations were examined between the exposed group and referents and tibial bone lead concentration and the neurobehavioural and neurophysiological outcomes of interest. RESULTS: Among the measures of peripheral nerve function, after controlling for confounders, sural sensory nerve evoked response amplitude, peroneal motor nerve compound motor action potential amplitude, vibrotactile thresholds of fingers and toes, and standing steadiness were significantly associated with exposure group. Among the neurobehavioural tests, hand-eye coordination, simple reaction time latency, trails B latency, symbol digit latency, serial digit, and learning error score were also significantly associated with exposure group after controlling for confounders. Exposed subjects had significantly more neuropsychiatric symptoms than the referents. Associations between tibial bone lead concentration and scores for vocabulary, vibrotactile thresholds of the fingers, and vibrotactile thresholds of the toes approached significance. CONCLUSIONS: Significant adverse central and peripheral neurological effects were found in a group of young adults 20 years after childhood environmental exposure to lead when compared with non-exposed controls. The absence of a significant association between neurological outcomes and tibial bone lead concentration, and the presence of significant associations between neurological outcomes and exposure group may be due to either the magnitude of measurement uncertainty in K x ray films relative to the actual tibial bone lead concentration in these young non-occupationally exposed subjects, or uncontrolled confounding of the exposure group.

Adult↗
PubMed1995

Neurotoxicity among pesticide applicators exposed to organophosphates.

OBJECTIVES: An epidemiological study of 90 male pesticide applicators licensed in New York was conducted to investigate the effect of exposure to organophosphate pesticides on the peripheral nervous system. METHODS: A cohort of farmers and pesticide applicators from New York State were questioned off season (November 1988-February 1989) and again during the spraying season (April 1989-August 1989) about the presence of several acute signs and symptoms. Short term exposure was validated by measuring the concentration of dimethylthiophosphate (DMTP), a metabolite of guthion, in urine. Chronic signs of subtle peripheral nerve damage were determined by vibration threshold sensitivity of the farmers and applicators tested during November 1988-February 1989 and compared with controls drawn from the general population who were tested during the same time period the next year (November 1989-February 1990). Vibration threshold sensitivity was determined for both the hands and feet. Long term exposure to pesticides was determined by questionnaire. RESULTS: Paired t tests show that mean vibration threshold scores were significantly higher for the dominant (P < 0.00) and non-dominant (P < 0.04) hands among pesticide applicators when compared with scores for population based controls individually matched on age, sex, and county of residence. CONCLUSIONS: A significant increase in mean vibration threshold sensitivity for the dominant and non-dominant hand suggests previous organophosphate exposure among pesticide applicators was associated with a loss of peripheral nerve function.

Adult↗
PubMed1994

The gut-brain peptide cyclo(His-Pro) is secreted in a pulsatile fashion in fasting humans.

Histidyl-proline diketopiperazine (CHP) is a cyclic dipeptide that is found in many animal tissues, most notably brain and gut. It has been found to have a variety of biologic actions and has been postulated to play a role in appetitive behavior and energy metabolism. This study was conducted in order to characterize the secretory pattern of CHP during a 24 h fast. Four subjects (2 obese and 2 lean) were studied during the latter 24 h of a 36 h fast. Blood was sampled every 10-15 min and assayed for CHP concentration using a specific radioimmunoassay. Analysis revealed that circulating CHP oscillates in humans and that diurnal variation occurred but only in the obese subjects.

Adult↗
PubMed1987

Present and future action on federal health care policy.

This article outlines the accomplishments made in health care legislation during 1986. Areas covered are the Consolidated Omnibus Budget Reconciliation Act, the Sixth Omnibus Reconciliation Act, budget increases for AIDS research, and the effect of the new tax law on health care. Also included is an overview of legislative goals for 1987.

Catastrophic Illness↗
PubMed1986

Effect of night and day on preterm infants in a newborn nursery: randomised trial.

The effect of alternating night and day on sleep, feeding, and weight gain in 41 healthy preterm infants was examined in a randomised controlled trial. Twenty infants from a night and day nursery, where the intensity of light and noise was reduced between 7 pm and 7 am, spent longer sleeping and less time feeding and gained more weight than 21 infants from a control nursery, where the intensity of light and noise was not reduced. Differences were significant and became apparent only after discharge home; they were still present three months after the expected date of delivery, when infants from the night and day nursery were an average of 0.5 kg heavier (p less than 0.02). These findings suggest that physical environment has an effect (either direct or indirect) on the subsequent behaviour of preterm infants and that exposure to night and day is beneficial.

Body Weight↗
PubMed1986

A case-control study of twin pairs discordant for Parkinson's disease: a search for environmental risk factors.

A previous study of twins with Parkinson's disease (PD) revealed low concordance, suggesting that genetic factors play a minor role in the etiology of PD. To identify possible environmental determinants of PD while maximally controlling for hereditary factors, 31 monozygotic twin pairs discordant for PD were interviewed by telephone. Information about possible risk factors was obtained from systematic and uniform interviews with cases and controls. The only statistically significant result was less cigarette smoking by PD patients (p less than 0.05). Thirteen dizygotic discordant twin pairs were evaluated with the same techniques, but there were no statistically significant differences between affected and unaffected twins.

Female↗
PubMed1976

Anticonnective tissue and other antitissue 'antibodies' in the sera of patients with coeliac disease compared with the findings in a mixed hospital population.

Serum IgG specificities directed against various components of basement membrane and reticulin have been described, and their incidence in 138 patients with coeliac disease has been compared with that in 110 hospital inpatients, 100 normal blood donors, and 1441 other patients. A wide variety of antitissue specificities were observed but only a few appeared to be of any significance. The 'antireticulin' specificities have been subdivided into different groups according to their distinctive histological staining patterns. Specificity directed primarily against endothelial basement membrane was found most frequently in the sera of patients with hiatus hernia (35%) or coeliac disease (22%). The same specificity was also observed in patients with myasthenia gravis and to a lesser extent in Crohn's disease and in a mixed group of patients with unspecified organic gastrointestinal disease. An epithelial basement membrane reactivity was found in patients with rheumatoid arthritis but only rarely in other conditions. Staining of perivascular connective tissue represented a third type of 'antireticulin' specificity. It was found only rarely, although in coeliac disease this reactivity was found more frequently in combination with other connective tissue specificities.

Adult↗