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Cyclic ADP ribose-mediated Ca2+ signaling in mediating endothelial nitric oxide production in bovine coronary arteries.

The present study tested the hypothesis that cyclic ADP ribose (cADPR) serves as a novel second messenger to mediate intracellular Ca2+ mobilization in coronary arterial endothelial cells (CAECs) and thereby contributes to endothelium-dependent vasodilation. In isolated and perfused small bovine coronary arteries, bradykinin (BK)-induced concentration-dependent vasodilation was significantly attenuated by 8-bromo-cADPR (a cell-permeable cADPR antagonist), ryanodine (an antagonist of ryanodine receptors), or nicotinamide (an ADP-ribosyl cyclase inhibitor). By in situ simultaneously fluorescent monitoring, Ca2+ transient and nitric oxide (NO) levels in the intact coronary arterial endothelium preparation, 8-bromo-cADPR (30 microM), ryanodine (50 microM), and nicotinamide (6 mM) substantially attenuated BK (1 microM)-induced increase in intracellular [Ca2+] by 78%, 80%, and 74%, respectively, whereas these compounds significantly blocked BK-induced NO increase by about 80%, and inositol 1,4,5-trisphosphate receptor blockade with 2-aminethoxydiphenyl borate (50 microM) only blunted BK-induced Ca2+-NO signaling by about 30%. With the use of cADPR-cycling assay, it was found that inhibition of ADP-ribosyl cyclase by nicotinamide substantially blocked BK-induced intracellular cADPR production. Furthermore, HPLC analysis showed that the conversion rate of beta-nicotinamide guanine dinucleotide into cyclic GDP ribose dramatically increased by stimulation with BK, which was blockable by nicotinamide. However, U-73122, a phospholipase C inhibitor, had no effect on this BK-induced increase in ADP-ribosyl cyclase activity for cADPR production. In conclusion, these results suggest that cADPR importantly contributes to BK- and A-23187-induced NO production and vasodilator response in coronary arteries through its Ca2+ signaling mechanism in CAECs.

Animals↗

Wavelet transform to quantify heart rate variability and to assess its instantaneous changes.

Heart rate variability is a recognized parameter for assessing autonomous nervous system activity. Fourier transform, the most commonly used method to analyze variability, does not offer an easy assessment of its dynamics because of limitations inherent in its stationary hypothesis. Conversely, wavelet transform allows analysis of nonstationary signals. We compared the respective yields of Fourier and wavelet transforms in analyzing heart rate variability during dynamic changes in autonomous nervous system balance induced by atropine and propranolol. Fourier and wavelet transforms were applied to sequences of heart rate intervals in six subjects receiving increasing doses of atropine and propranolol. At the lowest doses of atropine administered, heart rate variability increased, followed by a progressive decrease with higher doses. With the first dose of propranolol, there was a significant increase in heart rate variability, which progressively disappeared after the last dose. Wavelet transform gave significantly better quantitative analysis of heart rate variability than did Fourier transform during autonomous nervous system adaptations induced by both agents and provided novel temporally localized information.

Adrenergic beta-Antagonists↗

Real-time ultrasonic scan conversion via linear interpolation of oversampled vectors.

Scan conversion is required in order to display conventional B-mode ultrasonic signals, which are acquired along radii at varying angles, on standard Cartesian-coordinate video monitors. For real-time implementations, either nearest-neighbor or bilinear interpolation is usually used in scan conversion. If the sampling rate along each radius is high enough, however, the gray-scale value of a given pixel can be interpolated accurately using the nearest samples on two adjacent vectors. The required interpolation then reduces to linear interpolation. Oversampling by a factor of 2 along with linear interpolation was superior to bilinear interpolation of vectors sampled to match pixel-to-pixel spacing in 6 representative B-mode images. A novel 8-bit linear interpolation algorithm was implemented as a CMOS VLSI circuit using a readily available, high-level synthesis tool. The circuit performed 30 million interpolations per second. Arithmetic results produced by the 8-bit interpolator on 7-bit samples were virtually identical to IEEE-format, single-precision, floating-point results.

Algorithms↗

Crime, prostitution, drugs, and malingered insanity: female offenders' resistant strategies to abuse and domination.

Mizrahi female offenders have been described as passive victims propelled into crime, prostitution, and drug abuse as a result of traumatic childhood and life course experiences. This qualitative study adopts a postmodern critical orientation and Foucault's bottom-up microsocial analysis of power to examine the trajectories of resistance of 8 female offenders who break the silence to tell their life story. Analysis of narratives, informal conversations, and more focused, in-depth interviews with these women allow the deconstruction of the stereotype of the passive and helpless female offender. Using the sensitizing concepts of control, agency, and resistant efforts and letting the data speak, this research reconstructs female offending as a hidden script of resistance against intolerable socioeconomic deprivation and extreme forms of abuse.

Adult↗

Preferences need no inferences, once again: germinal elements in the public perceptions of genetically modified foods in Colombia.

This paper explores the public perceptions of genetically modified foods in Colombia in a phase considered germinal: the topic was too novel at the time of research. The analysis covers media, informal conversations, and the word associations made by a sample of residents in the city of Bogotá. The results show that the public capability of associating with the topic, even intuitively, is due to the availability of culture themes, the primary categories that help conceptual elaborations, and the construction of common-sense theories. Three themes are proposed: natural/artificial, tradition/change, and health/disease. It is argued that cultural themes are not only cognitive, but also affectively laden entities, which explains the evaluative force expressed by social beliefs. Acknowledging the relevance of the non-attitude thesis, the author suggests that people associate novel objects with latent cultural meanings, explaining why words, images, and metaphors are readily available in elaborating social knowledge.

Colombia↗

A Christmas without memories: Beliefs about grief and mothering--a clinical case analysis.

In clinical work using the Illness Beliefs Model, therapeutic leverage is focused on challenging constraining beliefs of family members that are contributing to their suffering. This challenge occurs in many ways, including offering alternative facilitating beliefs that may lead to healing rather than suffering. This article describes an exemplar of clinical work with a family who sought services in the Family Nursing Unit at the University of Calgary, with the presenting concern of unresolved grief. This analysis describes the therapeutic conversation that occurred between the family and a team of nurse clinicians, where the young woman's beliefs about grief and mothering were distinguished as beliefs that were contributing to her emotional pain and her belief in her mothering capabilities. The nursing team offered alternative beliefs of which the family rapidly embraced and, subsequently, experienced diminishment of the suffering previously experienced.

Adaptation, Psychological↗

Long-term effects of chemotherapy in patients with testicular cancer.

PURPOSE: Combination chemotherapy regimens that include cisplatin (CDDP) and bleomycin (BLE) result in the cure of the majority of patients with malignant germ cell tumors of the testis. We investigated the long-term damage of such chemotherapy to renal, pulmonary, and hearing function. PATIENTS AND METHODS: Forty-three patients with disseminated testicular carcinoma were studied 1.5 to 9.3 years (median, 4.1 years) after completion of chemotherapy. All 43 patients received CDDP; of these, 39 also received BLE, 27 vinblastine (VLB), and 27 etoposide (VP-16). Mean cumulative doses of individual cytotoxic drugs administered were CDDP 483 mg/m2 (range, 189 to 1,173 mg/m2), BLE 160 mg/m2 (range, 81 to 311 mg/m2), VLB 31 mg/m2 (range, 19 to 158 mg/m2), and VP-16 667 mg/m2 (range, 242 to 1,455 mg/m2). RESULTS: In the majority of cases, values of renal, pulmonary, and hearing function were within the normal range before treatment. An initial decrease in renal, pulmonary, and hearing function was observed, with recovery of pulmonary function at late follow-up. On average, a decrease of 15% in creatinine clearance rates was observed at late follow-up. Long-term effect on audiometric function was considerable, but frequencies affected were outside the range of conversational speech. With multivariate analysis, no overall relation between the cumulative doses of the individual drugs and the loss in organ function was found; the cumulative doses of CDDP and BLE only contributed approximately 30% to the loss in renal function and vital capacity, respectively. CONCLUSION: Chemotherapy-induced pulmonary toxicity is reversible, whereas nephrotoxicity and ototoxicity are not. However, the long-term effects of chemotherapy in testicular cancer patients were minor and not invalidating.

Adult↗

Human 3 beta-hydroxysteroid dehydrogenase/delta 5----4isomerase from placenta: expression in nonsteroidogenic cells of a protein that catalyzes the dehydrogenation/isomerization of C21 and C19 steroids.

The isolation, cloning, and expression of a cDNA insert complementary to mRNA encoding human 3 beta-hydroxysteroid dehydrogenase/delta 5----4isomerase is reported. The insert contains an open reading frame encoding a protein of 372 amino acids, the initial 29 amino acids corresponding to the N-terminal sequence identified from the purified human placental microsomal enzyme. The cDNA was inserted into a modified pCMV vector and expressed in COS-1 monkey kidney tumor cells. The expressed protein was similar in size to human placental microsomal 3 beta-hydroxysteroid dehydrogenase/delta 5----4isomerase, as detected by immunoblot analysis, and catalyzed the conversion of 17 alpha-hydroxypregnenolone to 17 alpha-hydroxyprogesterone, pregnenolone to progesterone, and dehydroepiandrosterone to androstenedione. Transfected COS cell homogenates, supplemented with NAD+, very efficiently oxidized 5 alpha-androstan-3 beta,17 beta-diol to 5 alpha-dihydrotestosterone and, upon addition of NADH, reduced 5 alpha-dihydrotestosterone to 5 alpha-androstan-3 beta,17 beta-diol. Thus, the dehydrogenation/isomerization steps of steroid biosynthesis can be catalyzed by a single polypeptide chain, which can metabolize all of the major physiological substrates.

17-alpha-Hydroxypregnenolone↗

FRL-1, a member of the EGF-CFC family, is essential for neural differentiation in Xenopus early development.

Recent studies indicate an essential role for the EGF-CFC family in vertebrate development, particularly in the regulation of nodal signaling. Biochemical evidence suggests that EGF-CFC genes can also activate certain cellular responses independently of nodal signaling. Here, we show that FRL-1, a Xenopus EGF-CFC gene, suppresses BMP signaling to regulate an early step in neural induction. Overexpression of FRL-1 in animal caps induced the early neural markers zic3, soxD and Xngnr-1, but not the pan-mesodermal marker Xbra or the dorsal mesodermal marker chordin. Furthermore, overexpression of FRL-1 suppressed the expression of the BMP-responsive genes, Xvent-1 and Xmsx-1, which are expressed in animal caps and induced by overexpressed BMP-4. Conversely, loss of function analysis using morpholino-antisense oligonucleotides against FRL-1 (FRL-1MO) showed that FRL-1 is required for neural development. FRL-1MO-injected embryos lacked neural structures but contained mesodermal tissue. It was suggested previously that expression of early neural genes that mark the start of neuralization is activated in the presumptive neuroectoderm of gastrulae. FRL-1MO also inhibited the expression of these genes in dorsal ectoderm, but did not affect the expression of chordin, which acts as a neural inducer from dorsal mesoderm. FRL-1MO also inhibited the expression of neural markers that were induced by chordin in animal caps, suggesting that FRL-1 enables the response to neural inducing signals in ectoderm. Furthermore, we showed that the activation of mitogen-activated protein kinase by FRL-1 is required for neural induction and BMP inhibition. Together, these results suggest that FRL-1 is essential in the establishment of the neural induction response.

Animals↗

Experimental identification of chemical carcinogens, risk evaluation, and animal-to-animal correlations.

Experimental methods for the identification of chemical carcinogens have been extensively developed, including animal bioassay methods, animal models for cancer induction at major organ sites, models for the study of the effects of carcinogens in cells and tissues in culture and methods for the study of molecular events (metabolic activation, binding and detoxification of carcinogens; DNA damage and repair; mutagenicity). Current sources of documentation on carcinogenicity data are reviewed. The number of "known carcinogens" will vary considerably, depending on the criteria adopted for accepting evidence of carcinogenicity. CRITERIA FOR THE EVALUATION OF RISKS, BENEFITS, AND TECHNOLOGICAL ALTERNATIVES FOR PUBLIC POLICY ON ENVIRONMENTAL CARCINOGENS ARE REVIEWED AND THE FOLLOWING STEPS DISCUSSED: registration of environmental chemical carcinogens and their uses; risk evaluation (considering sources, adequacy, quality and limits of the evidence; quantitative dose-response extrapolation within the same biological system; and species and model conversion factors); benefits evaluation; analysis of technological alternatives; comparative judgment and decision; open public documentation. The problem of animal-to-human correlations is considered, particularly for respiratory carcinogenesis. A laboratory approach is reviewed which includes: development and study of whole animal models for carcinogenesis, analysis of animal tissue responses to carcinogens in vivo and through in vitro culture methods for morphological and biochemical studies, and development of in vitro culture methods for human target tissues. This approach is aimed at providing an experimentally controlled and quantifiable method for the correlation of animal and human observations in carcinogenesis.

Animals↗

Transgender youth: invisible and vulnerable.

This study used three focus groups to explore factors that affect the experiences of youth (ages 15 to 21) who identify as transgender. The focus groups were designed to probe transgender youths' experiences of vulnerability in the areas of health and mental health. This involved their exposure to risks, discrimination, marginalization, and their access to supportive resources. Three themes emerged from an analysis of the groups' conversations. The themes centered on gender identity and gender presentation, sexuality and sexual orientation, and vulnerability and health issues. Most youth reported feeling they were transgender at puberty, and they experienced negative reactions to their gender atypical behaviors, as well as confusion between their gender identity and sexual orientation. Youth noted four problems related to their vulnerability in health-related areas: the lack of safe environments, poor access to physical health services, inadequate resources to address their mental health concerns, and a lack of continuity of caregiving by their families and communities.

Adolescent↗

Characterization of metabolic pathway of linoleic acid 9-hydroperoxide in cytosolic fraction of potato tubers and identification of reaction products.

Potato tubers are shown to contain a unique lipoxygenase pathway to form 9-hydroperoxy-10,12-octadecadienoic acid (9-HPODE) from linoleic acid. Here, we report the metabolic pathway of 9-HPODE in the cytosolic fraction and the characterization of enzymes involved in the conversion of metabolites. The analysis of enzymatic reaction products at pH 5.5 revealed the formation of 9-keto-10,12-octadecadienoic acid, 9-hydroxy-10,12-octadecadienoic acid, 9,10-epoxy-11-hydroxy-12-octadecenoic acid, 9,10,13-trihydroxy-11-octadecenoic acid, and 9,12,13-trihydroxy-10-octadecenoic acid. The cytosolic enzymes were separated by anion-exchange chromatography into two fractions E1 and E2, having molecular masses of 66 and 54 kDa, respectively. The enzyme fraction E1 only produced 9-keto-10,12-octadecadienoic acid, whereas E2 formed other products. The enzyme E1 showed higher reactivity with 13- and 9-hydroperoxide of alpha-linolenic acid than 9-HPODE, but no reaction with hydroxy fatty acids. In contrast, the enzyme E2 showed the highest reactivity with 9-HPODE, followed by hydroperoxides of alpha-linolenic acid and arachidonic acid. We also evaluated the antibacterial activity of hydroxy fatty acids against Erwinia carotovora T-29, a bacterium infecting potato tubers. Growth of the bacteria was suppressed more potently with 9- or 13-hydroxy fatty acids than dihydroxy or trihydroxy fatty acids, suggesting a role for the metabolites in the resistance of bacterial infection.

Chromatography, Gel↗

Absorption, distribution and elimination of alcohol: highway safety aspects.

Key aspects of the pharmacokinetics of alcohol are highly relevant to highway safety. Of particular pertinence are the partition of alcohol between various body tissues and fluids and the resulting alcohol concentration ratios for blood: breath and other body fluids, as well as the irregularity and short-term fluctuations of the blood and breath alcohol curves. Most alcohol pharmacokinetics parameters are subject to wide intersubject variability, as exemplified by peak blood alcohol concentrations reached on ingestion of identical weight-adjusted doses, time to peak after end of drinking and the rate of alcohol elimination from the blood. This great biological intersubject variability, when combined with sex-, age- and time-related differences, makes the blood alcohol information in widely distributed alcohol consumption nomograms and tables based on mean data inappropriate as a guide for the drinking behavior of individuals. Although there is good statistical correlation between the alcohol concentration of different body tissues and fluids in the fully postabsorptive state, wide individual variations from the population mean alcohol partition values exist. It is often impossible to determine whether the postabsorptive state has been reached at any given time. Those factors make it impossible or infeasible to convert the alcohol concentration of breath or urine to the simultaneous blood alcohol concentration with forensically acceptable certainty, especially under per se or absolute alcohol concentration laws. Inclusion of breath alcohol concentrations in drinking-driving statutes, as definitions or per se offense elements, makes unnecessary the conversion of breath alcohol analysis results into equivalent blood alcohol concentrations. Urine alcohol concentrations are inadequately correlated with blood alcohol concentrations or with driver impairment, and analysis of bladder urine is, therefore, inappropriate in traffic law enforcement. Significantly large sex-related differences in pharmacokinetic parameters have been demonstrated (e.g., in peak blood alcohol concentrations for weight-adjusted doses). The effects of age and time of day have been less extensively studies and are less clear. Breath and blood alcohol time curves are subject to short-term fluctuations from the trend line and other irregularities, and often do not follow the typical Widmark pattern. From the existing information on pharmacokinetics of alcohol and the characteristics and variability of blood and breath alcohol versus time curves, the following conclusions can be reached.(ABSTRACT TRUNCATED AT 400 WORDS)

Accident Prevention↗

Granddaughters' accounts of the influence of parental mediation on relational closeness with maternal grandmothers.

This study explores granddaughters' reports of the nature and impact of parental mediation on the development of their feelings of closeness toward their maternal grandmothers. Results from close-ended questions assessing granddaughters' perceptions of parental mediation and relational closeness indicated that closeness was predicted by mediation involving: visits alone with grandmothers, the absence of criticism of grandmothers, communication indicating the grandmothers were important persons, and less influence on conversations or activities. Qualitative analysis of granddaughters' accounts of the influence of parents illustrated what they perceived to be important issues in mediation. Additionally, accounts revealed the role of other family members in the relationship mediation process.

Adolescent↗

Comparison of two algorithms and their associated charges when evaluating adrenal masses in patients with malignancies.

OBJECTIVE: This study was performed to compare two proposed algorithms used when evaluating an adrenal mass discovered during staging evaluation of a patient with a known malignancy. Such evaluation was meant to lead to determination of the relative charges associated with each algorithm. SUBJECTS AND METHODS: Fifty-four patients with known malignancies who required evaluation of an adrenal mass underwent both chemical shift imaging (CSI) and CT-guided for CSI. The hospital charges incurred for each procedure and any associated complications were normalized using national relative-value scale charges and conversion factors. A decision analysis was performed to compare the relative charges that would have been incurred if adrenal MR imaging had been performed in all patients, followed by CT-guided biopsy only in those patients with MR findings not diagnostic of adrenocortical adenoma, and the relative charges incurred if only CT-guided adrenal biopsy had been performed in every patient. RESULTS: Twenty-three (43%) of 54 adrenal masses were shown to be metastases by CT-guided biopsy. The sensitivity and specificity of CSI for the diagnosis of adrenocortical adenoma were 94% and 100%, respectively. The charges incurred by performing MR imaging as the initial examination with subsequent CT-guided biopsy only in those patients with CSI findings not diagnostic of adenoma would have been similar to those incurred by first performing CT-guided adrenal biopsy in every patient. CONCLUSION: CSI is an accurate, noninvasive technique for evaluating adrenal masses in patients with cancer. If CT-guided biopsy is used only when CSI is not diagnostic of adrenocortical adenoma, the associated charges would be virtually the same as when CT-guided biopsy is performed as the first test in every patient. Moreover, biopsies could have been avoided in 54% of these patients.

Adrenal Cortex Neoplasms↗

Biomarker responses in river otters experimentally exposed to oil contamination.

Investigations in Prince William Sound (Alaska, USA) following the Exxon Valdez oil spill (EVOS) revealed that river otters (Lontra canadensis) on oiled shores had lower body mass and elevated values of biomarkers, than did otters living on nonoiled shores. In addition, otters from oiled areas selected different habitats, had larger home ranges, and less diverse diets than animals living in nonoiled areas. These differences between river otters from oiled shores and those from nonoiled areas strongly suggested that oil contamination had an effect on physiological and behavioral responses of otters. In this study, we explored the effects of crude oil contamination on river otters experimentally. We hypothesized that exposure to oil would result in elevated values of biomarkers, indicating induced physiological stress. Fifteen wild-caught male river otters were exposed to two levels of weathered crude oil (i.e., control, 5 ppm/day/kg body mass, and 50 ppm/day/kg body mass) under controlled conditions in captivity at the Alaska Sealife Center in Seward (Alaska, USA). Responses of captive river otters to oil ingestion provided mixed results in relation to our hypotheses. Although hemoglobin (Hb, and associated red blood cells) and white blood cells, and possibly interleukin-6 immunoreactive responded in the expected manner, other parameters did not. Aspartate aminotransferase, alanine aminotransferase, and haptoglobin (Hp), did not increase in response to oiling or decreased during rehabilitation. Conversely, principle-component analysis identified values of alkaline phosphatase as responding to oil ingestion in river otters. Our results suggested that opposing processes were concurring in the oiled otters. Elevated production of Hp in response to tissue damage by hydrocarbons likely occurred at the same time with increased removal of Hp-Hb complex from the serum, producing an undetermined pattern in the secretion of Hp. Thus, the use of individual biomarkers as indicators of exposure to pollutants may lead to erroneous conclusions because interactions in vivo can be complicated and act in opposite directions. Additionally, the biomarkers used in investigating effects of oiling on live animals usually are related to the heme molecule. Because of the opposing processes that may occur within an animal, data from a suite of heme-related biomarkers may produce results that are difficult to interpret. Therefore, we advocate the exploration and development of other biomarkers that will be independent from the heme cycle and provide additional information to the effect of oiling on live mammals.

Alaska↗

Management factors affecting the risk for vesicular stomatitis in livestock operations in the western United States.

OBJECTIVE: To identify management factors affecting the risk of animals developing vesicular stomatitis (VS). DESIGN: Case-control study. ANIMALS: Horses, cattle, and sheep with suspected vesicular stomatitis on 395 premises in Colorado, New Mexico, Utah, and Arizona. PROCEDURE: Data were collected during the VS outbreak of 1997. Diagnosticians interviewed livestock owners and completed a supplemental questionnaire. Cases were defined as those premises that had a completed questionnaire and had > or = 1 animal positive for VS. Control premises were all premises investigated that had a completed questionnaire and on which the animals had been tested but VS was not detected. RESULTS: Animals that had access to a shelter or barn had a reduced risk of developing VS (OR, 0.6; 95% confidence interval [CI], 0.35 to 0.99). This effect was more pronounced for equine premises (OR, 0.5; 95% CI, 0.3 to 0.9). Conversely, during an adjusted analysis on equine premises, risk of developing disease was increased slightly where animals had access to pasture (OR, 2.01; 95% CI, 1.1 to 3.7). On all premises where owners reported insect populations were greater than normal, odds of developing disease were significantly increased (OR, 2.5; 95% CI, 1.47 to 4.47). Premises with animals housed < 0.25 miles from running water were more than twice as likely to have clinical signs of VS (OR, 2.6; 95% CI, 1.32 to 5.0). CONCLUSIONS AND CLINICAL RELEVANCE: These results support reports of others that suggest biting insects are a vector in VS virus transmission. Management practices to reduce exposure to biting insects might reduce the risk of VS.

Animal Husbandry↗

[Analysis criteria's influence on incidence and factors associated tuberculin conversion in health care workers].

BACKGROUND: To know from two different criteria, CDC's and Spanish national consensus (NC), the tuberculin conversion rate and the factors associated to this phenomenon. PATIENTS AND METHODS: A retrospective cohort study was designed over 475 health care workers. Risk factors were identified by using a Cox's proportional hazards model for each criteria. RESULTS: Not being vaccinated with BCG appears to be a risk factor in NC model 5.37 (CI 95%: 2.21-13.00) and does not in CDC. There was a difference of 45% between both incidence density rates. CONCLUSIONS: We did not find a total concordance between the results from the two models.

Adult↗