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Biomedical subjects

M B Murphy

Publications and source records attributed to M B Murphy.

At least 19 recordsLinked to original sources
PubMed2006

Sediment TCDD-EQs and EROD and MROD activities in Ranid frogs from agricultural and nonagricultural sites in Michigan (USA).

In vitro studies have demonstrated atrazine-mediated induction of 7-ethoxyresorufin O-deethylase (EROD) activity. EROD is an enzyme active in the metabolism of many compounds, including many xenobiotics. These studies have suggested that atrazine may affect reproductive function by altering steroid metabolism. The goal of this study was to determine whether relationships could be detected between measured atrazine concentrations in surface waters and the liver-somatic index (LSI) and EROD and 7-methoxyresorufin O-deethylase (MROD) activities in the livers of ranid frogs. In addition, sediment dioxin toxic equivalents (TCDD-EQs) were determined using the H4IIE-luc cell bioassay. Adult and juvenile green frogs (Rana clamitans), bullfrogs (R. catesbeiana), and Northern leopard frogs (R. pipiens) were collected from areas with extensive corn cultivation and areas where there was little agricultural activity in south central Michigan in the summer of 2003. Atrazine concentrations at nonagricultural sites ranged from less than the limit of quantification (0.17 microg atrazine/L) to 0.23 microg atrazine/L and did not exceed 1.2 microg atrazine/L at agricultural sites. Sediment TCDD-EQs were measurable only at one agricultural site. Of the measured parameters, only LSI values in adult male frogs differed significantly between agricultural and nonagricultural sites, with greater values observed at agricultural sites. In green frogs, EROD and MROD activities were measurable in both adult and juvenile frogs and were similar among sites. Median EROD activities ranged from 13 to 21 pmol/min/mg protein in adult male green frogs and from 5 to 13 pmol/min/mg protein in adult female green frogs. Juvenile frogs had greater EROD and MROD activities than adult frogs. Bullfrogs and leopard frogs had greater activities than did green frogs. Atrazine concentrations were significantly and negatively correlated with MROD activity in adult male green frogs (Spearman R = -0.800). LSI and EROD and MROD activities of adult female or juvenile green frogs were not significantly correlated with atrazine concentrations. These results suggest that atrazine does not appear to have a consistent association with EROD or MROD activities in wild-caught green frogs.

Agriculture↗
PubMed2006

Plasma steroid hormone concentrations, aromatase activities and GSI in ranid frogs collected from agricultural and non-agricultural sites in Michigan (USA).

The triazine herbicide atrazine has been hypothesized to disrupt sexual development in frogs by up-regulating aromatase activity, resulting in greater estradiol (E2) concentrations and causing feminization in males. The goal of this study was to collect native ranid frogs from atrazine-exposed ponds and determine whether relationships exist between measured atrazine concentrations and the gonadosomatic index (GSI), plasma concentrations of testosterone (T), E2 or 11-ketotestosterone (KT), or with aromatase activity. In the summer of 2002 and 2003, adult and juvenile green frogs (Rana clamitans), bullfrogs (R. catesbeiana) and Northern leopard frogs (R. pipiens) were collected from areas with extensive corn cultivation and areas where there was little agricultural activity in south-central Michigan. Atrazine concentrations were below the limit of quantification at non-agricultural sites. Atrazine concentrations did not exceed 2 microg/L at most agricultural sites, but a concentration of 250 microg atrazine/L was measured in one sample from one site in 2002. Plasma steroid concentrations varied among locations. Aromatase activity was measurable in less than 11% of testes in adult males, and in less than 4% of testes in juvenile males. Median aromatase activities in ovaries of adult females ranged from 3 to 245 pmol/h/mg protein, and maximum activities were 2.5-fold greater in juveniles than in adults. Atrazine concentrations were not significantly correlated with any of the parameters measured in this study. These results indicate that atrazine does not up-regulate aromatase in green frogs in the wild, and does not appear to affect plasma steroid hormone concentrations.

Animals↗
PubMed2005

Atrazine concentrations, gonadal gross morphology and histology in ranid frogs collected in Michigan agricultural areas.

The triazine herbicide atrazine has been suggested to be a potential disruptor of normal sexual development in male frogs. The goals of this study were to collect native ranid frogs from sites in agricultural and non-agricultural areas and determine whether hypothesised atrazine effects on the gonads could be observed at the gross morphological and histological levels. Juvenile and adult green frogs (Rana clamitans), bullfrogs (R. catesbeiana) and leopard frogs (R. pipiens) were collected in the summers of 2002 and 2003. Atrazine concentrations were below the limit of quantification at non-agricultural sites, and concentrations did not exceed 2 microg/L at most agricultural sites. One concentration greater than 200 microg atrazine/L was measured once at one site in 2002. Hermaphroditic individuals with both male and female gonad tissue in either one or both gonads, were found at a low incidence at both non-agricultural and agricultural sites, and in both adults and juveniles. Testicular oocytes (TO) were found in male frogs at most of the sites, with the greatest incidence occurring in juvenile leopard frogs. TO incidence was not significantly different between agricultural and non-agricultural sites with the exception of juveniles collected in 2003. Atrazine concentrations were not significantly correlated with the incidence of hermaphroditism, but maximum atrazine concentrations were correlated with TO incidence in juvenile frogs in 2003. However, given the lack of a consistent relationship between atrazine concentrations and TO incidence, it is more likely the TOs observed in this study result from natural processes in development rather than atrazine exposure.

Agrochemicals↗
PubMed2002

Testing cognitive function in elderly populations: the PROSPER study. PROspective Study of Pravastatin in the Elderly at Risk.

OBJECTIVES: For large scale follow up studies with non-demented patients in which cognition is an endpoint, there is a need for short, inexpensive, sensitive, and reliable neuropsychological tests that are suitable for repeated measurements. The commonly used Mini-Mental-State-Examination fulfils only the first two requirements. METHODS: In the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), 5804 elderly subjects aged 70 to 82 years were examined using a learning test (memory), a coding test (general speed), and a short version of the Stroop test (attention). Data presented here were collected at dual baseline, before randomisation for active treatment. RESULTS: The tests proved to be reliable (with test/retest reliabilities ranging from acceptable (r=0.63) to high (r=0.88) and sensitive to detect small differences in subjects from different age categories. All tests showed significant practice effects: performance increased from the first measurement to the first follow up after two weeks. CONCLUSION: Normative data are provided that can be used for one time neuropsychological testing as well as for assessing individual and group change. Methods for analysing cognitive change are proposed.

Aged↗
PubMed2001

Werner syndrome protein is regulated and phosphorylated by DNA-dependent protein kinase.

DNA double-strand breaks (DSBs) are a highly mutagenic and potentially lethal damage that occurs in all organisms. Mammalian cells repair DSBs by homologous recombination and non-homologous end joining, the latter requiring DNA-dependent protein kinase (DNA-PK). Werner syndrome is a disorder characterized by genomic instability, aging pathologies and defective WRN, a RecQ-like helicase with exonuclease activity. We show that WRN interacts directly with the catalytic subunit of DNA-PK (DNA-PK(CS)), which inhibits both the helicase and exonuclease activities of WRN. In addition we show that WRN forms a stable complex on DNA with DNA-PK(CS) and the DNA binding subunit Ku. This assembly reverses WRN enzymatic inhibition. Finally, we show that WRN is phosphorylated in vitro by DNA-PK and requires DNA-PK for phosphorylation in vivo, and that cells deficient in WRN are mildly sensitive to ionizing radiation. These data suggest that DNA-PK and WRN may function together in DNA metabolism and implicate WRN function in non-homologous end joining.

Androstadienes↗
PubMed2000

The influence of physical activity on the variability of ambulatory blood pressure.

The aim of this study was to assess the contribution of physical activity levels to blood pressure (BP) variability, and to assess the effect age, gender, body mass index, and use of antihypertensive medications on this relationship. We simultaneously monitored 24-h ambulatory BP by automated recorder and activity by actigraphy in 431 patients. Mean activity scores for the 5, 10, 15, and 20 min preceding each BP measurement were calculated, and BP and heart rate were related to these variables using linear mixed model regression. Various patient characteristics were added to the mixed model as covariates. Patients were heterogeneous in age (48 +/- 13 years), sex (49% men), and average 24-h BP (132/81 +/- 15/10 mm Hg). Mean daytime activity level was 44 +/- 15 U. During the daytime, systolic BP (r = 0.33), diastolic BP (r = 0.29), and heart rate (r = 0.42) correlated best with the average activity for the 15 min preceding each measurement (P < .001). Variance was very high, with activity explaining from 0% to 62% of BP variability for different individuals. Men and the obese had a greater reactivity of systolic BP to activity; older patients and those on antihypertensive therapy had a lower reactivity of heart rate. Blood pressure level is significantly associated with physical activity, but the percentage of variance of BP explained by physical activity varies greatly between individuals. Correlation is strongest between BP and average activity integrated over the previous 15 min. Much of the variance in blood pressure remains unexplained.

Adolescent↗
PubMed2000

Nocturnal blood pressure dipping: a consequence of diurnal physical activity blipping?

This study was designed to describe the interaction between physical activity (PA), quantified objectively by electronic activity monitors, and ambulatory blood pressure (ABP), and to test the hypothesis that modifying daily PA can effect significant changes in the diurnal variation in blood pressure and may result in altered dipping/nondipping status of an individual. Initially, 70 individuals underwent simultaneous ABP and electronic activity monitoring (actigraph devices manufactured by Gaewihler Electronics, Switzerland) over a 24-h period. Then, in a prospective study, the dipping/nondipping status of 43 subjects was assessed using ABP recorded over two 24-h periods of differing activity levels. Of the 70 subjects (age 49 +/- 11 years, 42 male) the diurnal variation in systolic blood pressure (20 +/- 12%, step-up from night [120 +/- 12 mm Hg] to day [144 +/- 13 mm Hg]) and diurnal variation in PA score (increment from sleep, 44 +/- 17 units) correlated significantly (R2 = 0.29; P < .05). Of the 43 subjects who underwent ABP monitoring on a more active day, four had a nondipping BP profile; 12 of these same 43 subjects had a nondipping BP profile when monitored on a less active day (chi2 = 4.9; P < .05). These results provide a quantitative description of the contribution of PA, including the sleep/awake status, to blood pressure variation in a group of normotensive and hypertensive individuals. The magnitude of this effect underscores the importance of interpreting 24-h ABP data only in the presence of adequately quantified activity data.

Adult↗
PubMed2000

Dopamine: a role in the pathogenesis and treatment of hypertension.

The catecholamine dopamine (DA), activates two distinct classes of DA-specific receptors in the cardiovascular system and kidney--each capable of influencing systemic blood pressure. D1 receptors on vascular smooth muscle cells mediate vasodilation, while on renal tubular cells they modulate sodium excretion. D2 receptors on pre-synaptic nerve terminals influence noradrenaline release and, consequently, heart rate and vascular resistance. Activation of both, by low dose DA lowers blood pressure. While DA also binds to alpha- and beta-adrenoceptors, selective agonists at both DA receptor classes have been studied in the treatment of hypertension. An unfavourable side-effect profile (largely nausea and orthostasis) have precluded wide use of D2 agonists. In contrast, the D1 selective agonist fenoldopam has been licensed for the parenteral treatment of severe hypertension. Apart from inducing systemic vasodilation it induces a diuresis and natriuresis, enhanced renal blood flow, and a small increment in glomerular filtration rate. Evidence is emerging that abnormalities in DA production, or in signal transduction of the D1 receptor in renal proximal tubules, may result in salt retention and high blood pressure in some humans and in several animal models of hypertension.

Animals↗
PubMed2000

Ambulatory blood pressure monitoring: which arm?

To determine the effects of routinely selecting the nondominant arm for ambulatory blood pressure monitoring (ABPM) on estimates of patients' blood pressure (BP) and to evaluate the practise of using manual BP from one arm and ambulatory BP from the other on the estimation of white coat effect (WCE), an observational study was conducted in 10 volunteers, exhibiting an interarm resting clinic systolic BP (SBP) difference > or =10 mm Hg. The main outcome measures were: (i) average ambulatory SBP measured on right and left arm simultaneously during 24 h, and (ii) estimate of WCE derived, by current practise, as the difference between the referral clinic BP (the higher of the manual readings from both arms) and ambulatory non-dominant arm BP, contrasted with the WCE calculated as the difference between clinic and ambulatory readings from the same arm (the arm with the higher manual readings). The supine referral clinic SBP was 16+/-6 mm Hg higher in the right compared with the left arm. Average 24 h ambulatory SBP was 6+/-7 mm Hg higher in the right arm (range +17 to -3 mm Hg), P = 0.025. Diastolic BP measurements mirrored the systolic findings. One-third of the WCE, estimated by current practise, could be attributed to inconsistency in the choice of arm for BP measurement. Thus, inconsistency in the selection of arms for BP measurement, by different techniques, may confound estimation of patients' cardiovascular morbidity risk.

Arm↗
PubMed2000

Physical activity level is an independent predictor of the diurnal variation in blood pressure.

OBJECTIVE: The aim of this study was to define the relationship between physical activity and the magnitude of the percentage fall in blood pressure at night (nocturnal dip). METHODS: We simultaneously monitored 24-h ambulatory blood pressure and measured physical activity by actigraphy in 434 patients. Blood pressure was measured every 20 min; the actigraph integrated an activity score every 10 s. Mean daytime and night-time activity were calculated from mean scores for the 15 min preceding each blood pressure measurement. Nocturnal dip in systolic and diastolic blood pressure (SBP and DBP) were regressed on mean (log-transformed) daytime activity. Mean night-time activity, age, gender, smoking status, body mass index (BMI) and clinic blood pressure were added into a multiple linear regression. RESULTS: The patient group was heterogeneous in age, gender and mean 24-h blood pressure. Mean daytime activity level was significantly and positively associated with the magnitude of the nocturnal dip in both SBP and DBP. Increased night-time activity was significantly associated with a smaller nocturnal dip. Older patients had a smaller nocturnal dip per log unit daytime activity. Nocturnal dip in SBP was greater in males, and smaller in those taking antihypertensive medications. Smoking, BMI and clinical blood pressure level were not associated with the extent of the nocturnal dip after adjustment for other factors. CONCLUSIONS: Daytime and night-time physical activity levels are independently and significantly predictive of the magnitude of the nocturnal dip in blood pressure. Variation in activity may confound interpretation of 24-h ambulatory blood pressure monitoring, and contribute to the poor reproducibility of dipper status.

Adult↗
PubMed2000

Electronic activity-monitor-derived sleeping and awake times and diurnal variation of blood pressure.

BACKGROUND: Results of a number of studies have indicated that target-organ damage is more pronounced in non-dippers, those in whom the blood pressure falls by less than 10% with the onset of sleep, than it is in dippers with comparable clinic blood pressures. However, the standard use of arbitrarily defined daytime and night-time periods, rather than precise estimates of sleeping time and awake time, could limit the accuracy of estimates of diurnal variation of blood pressure and hence of dipping status. DESIGN AND METHODS: In this study of 102 consecutive patients undergoing ambulatory blood pressure monitoring we compared activity-derived estimates of sleeping and awake blood pressures using electronic activity monitoring and diary records with estimates determined using pre-defined day and night-time periods. The dipping/non-dipping status of each subject was assessed using these three different techniques for defining the awake/asleep time periods. RESULTS: The sleeping/awake times based on the activity monitor, diary and default data were 2356 h+/-55 min/0754 h+/-50 min, 2326 h+/-61 min/0722 h+/-72 min and 2300 h and 0700 h respectively. The percentage systolic/diastolic falls in blood pressure were 18+/-6/18+/-7% with six non-dippers (activity-monitor-derived data), 16+/-6/17+/-8% and 12 non-dippers (diary data) and 13+/-7/15+/-7% and 21 non-dippers (using the pre-set daytime and night-time periods). DISCUSSION: Results of this study demonstrate that the extent of the diurnal variation in blood pressure (and hence dipping status) can differ depending on the technique used to define periods of wakefulness and sleep.

Adolescent↗
PubMed1999

The design of a prospective study of Pravastatin in the Elderly at Risk (PROSPER). PROSPER Study Group. PROspective Study of Pravastatin in the Elderly at Risk.

The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) is a randomized, double-blind, placebo-controlled trial designed to test the hypothesis that treatment with pravastatin will diminish risk of subsequent major vascular events in a cohort of men and women (70 to 82 years old) with preexisting vascular disease or significant risk of developing this condition. Five thousand eight hundred four men and women in addition to receiving advice on diet and smoking, have been randomized equally to treatment with 40 mg pravastatin/day or matching placebo in 3 centers (Cork, Ireland, Glasgow, Scotland, and Leiden, The Netherlands). Following an average 3.5-year intervention period, a primary assessment will be made of the influence of this therapy on major vascular events (a combination of coronary heart disease, death, nonfatal myocardial infarction, and fatal and nonfatal stroke). A number of additional analyses will also be conducted on the individual components of the primary end point, on men, on women, and on subjects with and without previous evidence of vascular disease. Finally, an assessment will be made of the effects of treatment on cognitive function, disability, hospitalization or institutionalization, vascular mortality, and all-cause mortality.

Aged↗
PubMed1999

Molecular characterization and immunolocalization of Dictyostelium discoideum protein phosphatase 2A.

Protein phosphatase 2A (PP2A) was previously purified from Dictyostelium and biochemically characterized. The purified PP2A holoenzyme was composed of a 37 kDa catalytic 'C-subunit', a 65 kDa 'A-subunit' and a 55 kDa 'B-subunit'. We report here the characterization of the genes encoding the Dictyostelium PP2A subunits as well as the immunolocalization of the PP2A subunits in Dictyostelium. The cDNAs encoding the B- and C-subunits were isolated from a Dictyostelium library and the deduced amino acid sequences reveal strong conservation with the mammalian PP2A homologues. Southern blot analysis suggests that each of the PP2A subunit genes is present in a single copy. The PP2A subunits were localized mainly to the cytosol in Dictyostelium cells. However, immunofluorescence confocal microscopy demonstrates that the B-subunit of PP2A is highly enriched in centrosomes, suggesting a potential role for this PP2A regulatory subunit in the centrosomal function.

Amino Acid Sequence↗