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Biomedical subjects

M Whiteman

Publications and source records attributed to M Whiteman.

At least 37 records · Page 2Linked to original sources
PubMed2001

Raised levels of F(2)-isoprostanes and prostaglandin F(2alpha) in different rheumatic diseases.

OBJECTIVE: To evaluate oxidative injury and inflammatory status in various rheumatic diseases by measuring the levels of isoprostanes and prostaglandins in serum and synovial fluid. METHODS: The concentrations of 8-iso-PGF(2alpha) (F(2)-isoprostane indicating oxidative injury) and 15-keto-dihydro-PGF(2alpha) (a major metabolite of prostaglandin F(2alpha)) were measured in both serum and synovial fluid aspirated from 26 patients with various arthritic diseases, including rheumatoid arthritis (RA), reactive arthritis (ReA), psoriatic arthritis (PsA), and osteoarthritis (OA). These prostaglandin derivatives were also measured in serum samples collected from 42 healthy control subjects. RESULTS: Overall, serum levels of 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha) were much higher in patients with arthritic diseases than in the healthy control subjects. The levels of 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha) in synovial fluid aspirated from knee joints were also high and varied among various types of arthritic patients. Although the synovial fluid level of these prostaglandin derivatives was sometimes higher than in the corresponding serum sample, this was not a consistent finding. Overall, there was no correlation between serum and synovial fluid levels of 8-iso-PGF(2alpha), or between serum and synovial fluid levels of 15-keto-dihydro-PGF(2alpha). However, a strong relation was found between the levels of 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha,) in both serum (r(s)=0.53, p<0.001) and synovial fluid (r(s)=0.62, p<0.001). CONCLUSIONS: These data suggest that both free radical mediated oxidative injury and cyclo-oxygenase dependent inflammatory responses are closely correlated in various types of arthritis.

Adult↗
PubMed2000

A reevaluation of the peroxynitrite scavenging activity of some dietary phenolics.

Peroxynitrite is implicated in many diseases. Hence, there is considerable interest in potential therapeutic peroxynitrite scavengers. Diet-derived phenolics have been claimed to be powerful peroxynitrite scavengers. However, the reactivity of peroxynitrite can be significantly modified by bicarbonate and this has not been considered in evaluations of the scavenging activity of phenols. Bicarbonate (25 mM) significantly decreased the ability of several phenolic compounds (caffeic acid, o- and p-coumaric acid, gallic acid, ferulic acid) but not others (catechin and epicatechin) to inhibit peroxynitrite-mediated tyrosine nitration. Bicarbonate (25 mM) also decreased the ability of catechin, epicatechin, quercetin and ferulic acid but not chlorogenic acid, gallic acid, caffeic acid and o-coumaric acid to inhibit peroxynitrite-mediated alpha(1)-antiproteinase inactivation. These results show that physiological concentrations of bicarbonate substantially modify the ability of dietary phenolics to prevent peroxynitrite-mediated reactions. When assessing compounds for peroxynitrite scavenging, experiments should be conducted in the presence of bicarbonate to avoid misleading results.

Bicarbonates↗
PubMed2000

Nitrite-induced deamination and hypochlorite-induced oxidation of DNA in intact human respiratory tract epithelial cells.

No modification of purine or pyrimidine bases was observed when isolated DNA was incubated with 1 mM nitrite at pH 7.4. However, exposure of human bronchial epithelial cells in culture medium at pH 7.4 to nitrite at concentrations of 100 microM or greater led to deamination of purine bases in cellular DNA. Deamination was more extensive in cells exposed to lower extracellular pH values and higher nitrite concentrations. Significant increases in the levels of xanthine and hypoxanthine, putative deamination products of guanine and adenine, respectively, were observed in DNA from nitrite-treated cells but no rise in any base oxidation products such as 8-hydroxyguanine. This pattern of damage suggests that exposure of cells to nitrite (even at pH 7.4) leads to intracellular generation of "reactive nitrogen species" capable of deaminating purines in DNA. In addition, significant DNA strand breakage occurred in nitrite-treated cells. The time course of base damage suggested that the repair of deaminated purine lesions in these cells is slow. By contrast, DNA isolated from cells exposed to hypochlorous acid (HOCl) has significant oxidation of pyrimidine bases and chlorination of cytosine but little oxidation of purines. Exposure of cells to both species (NO(2)(-) plus HOCl) potentiated the oxidative DNA base damage observed but decreased the extent of deamination. We hypothesize that this is due to the formation of nitryl chloride (NO(2)Cl) from reaction of HOCl with *NO(2)(-). The relevance of our observations to events in the stomach and respiratory tract, at sites of inflammation, and in ischemic tissues is discussed.

Bronchi↗
PubMed2000

The influence of maternal smoking during pregnancy on the toddler's negativity.

OBJECTIVE: To extend previous studies by looking at the effect of the mother's smoking during pregnancy on her toddler's negative behavior. DESIGN: A survey consisting of a structured questionnaire was administered to the mothers of 2-year-old toddlers. SETTING: The subjects were drawn from a community sample, as part of a larger study of mothers and their children. SUBJECTS: The subjects were 99 toddlers and their mothers taken from a community sample. Fifty-two of the mothers smoked throughout pregnancy, while 47 either stopped smoking during pregnancy or started smoking after childbirth. MEASURES: The measures consisted of scales with adequate psychometric properties, which, for the most part, were adapted from the literature. Measures included assessment of smoking behavior, the mother's personality/behavior, perinatal variables, demographic variables, and aspects of the mother-child relationship. RESULTS: Using logistic regression analyses, maternal smoking during pregnancy was found to be related to negativity in the child, controlling for demographic factors, perinatal factors, maternal personality attributes, and the mother-child relationship. CONCLUSIONS: The findings suggest that maternal smoking during pregnancy has an adverse effect on the child's negativity, and that a decrease in maternal smoking during pregnancy might be expected to lead to a decrease in the child's negativity. The relationship of maternal smoking during pregnancy and early childhood negativity to other problem behaviors remains to be explored.

Adult↗
PubMed2000

Individual latent growth curves in the development of marijuana use from childhood to young adulthood.

The present study was designed to examine the relationship between unconventionality and marijuana use over time. The sample for this paper consisted of 532 male and female participants interviewed during early adolescence, late adolescence, their early twenties, and their late twenties. Latent growth modeling was used. The findings indicated that (1) the influence of initial unconventionality (T2) on initial marijuana use (T2) was stronger for males, (2) unconventionality at T2 was not significantly related to overall rate of growth in marijuana use, and (3) change in unconventionality was related to overall growth rate of marijuana use. The implications of the findings for prevention and treatment are discussed.

Adolescent↗
PubMed2000

Longitudinally foretelling drug use in the late twenties: adolescent personality and social-environmental antecedents.

This research focuses on the interrelation of the parent-child attachment, unconventionality, friends' drug use, and the young adult's use of drugs. Data were collected from participants at 4 points in time: early adolescence, late adolescence, early 20s, and late 20s. Data were collected from mothers at the 3 points in time that corresponded with the first 3 collections of data from their children. Both the youths and their mothers were individually interviewed. The findings indicated that the effect of parent-child mutual attachment was mediated through early adolescent personality attributes of greater responsibility, less rebelliousness, and intolerance of deviance. These non-drug-prone personality and behavioral attitudes, in turn, insulated the young adult from affiliating with drug-using peers, and these attitudes were related to less drug use in the early 20s and ultimately in the late 20s. The results suggest that interventions focused on enhancing parent-child mutual attachment should result in a reduction of the risk factors conducive to drug use during the late 20s. The fact that these findings cover a decade and a half, from early adolescence to the late 20s, underscores the significance of placing drug use in a perspective that includes familial and behavioral aspects.

Adolescent↗
PubMed2000

The gastrointestinal tract: a major site of antioxidant action?

Diets rich in fruits and vegetables delay the onset of many age-related diseases, and contain a complex mixture of antioxidants (including ascorbate, carotenoids, vitamin E and other phenolics such as the flavonoids). However, diet also contains pro-oxidants, including iron, copper, H2O2, haem, lipid peroxides and aldehydes. Nitrite is frequently present in diet, leading to generation of reactive nitrogen species in the stomach. In considering the biological importance of dietary antioxidants, attention has usually focussed on those that are absorbed through the gastrointestinal tract into the rest of the body. In the present paper we develop the argument that the high levels of antioxidants present in certain foods (fruits, vegetables, grains) and beverages (e.g. green tea) play an important role in protecting the gastrointestinal tract itself from oxidative damage, and in delaying the development of stomach, colon and rectal cancer. Indeed, carotenoids and flavonoids do not seem to be as well absorbed as vitamins C and E. Hence their concentrations can be much higher in the lumen of the GI tract than are ever achieved in plasma or other body tissues, making an antioxidant action in the GI tract more likely. Additional protective mechanisms of these dietary constituents (e.g. effects on intercellular communication, apoptosis, cyclooxygenases and telomerase) may also be important.

Animals↗
PubMed2000

Effects of parent personality, upbringing, and marijuana use on the parent-child attachment relationship.

OBJECTIVE: To examine the predictors of the quality of the parent-child attachment relationship among a sample of 248 young adults with children. METHOD: In this longitudinal study, data were collected during early adulthood in 1992 and in 1996/1997 via a structured questionnaire. Using logistic regression and multiple regression analyses, the authors assessed the extent to which participants' personality attributes, substance use, and relationships with their mothers predicted the quality of the parent-child bond. RESULTS: Logistic regression models showed that participants with certain personality attributes (e.g., high sensitivity), less frequent marijuana use, or a close relationship with their mothers had a greater likelihood of having a close parent-child attachment relationship with their own children at a later time. Regression analysis also showed that the risk of earlier substance use on the parent-child relationship was offset by protective factors in the parents' personality domain. In addition, protective factors in the various parental domains synergistically interacted with a low frequency of marijuana use, relating to a closer parent-child attachment relationship. CONCLUSIONS: The findings suggest that certain parenting styles are transmitted across generations and interventions in the personality and drug use domains can help increase the likelihood that parents will form close attachment relationships with their own children.

Adolescent↗
PubMed2000

Longitudinal pathways to condom use: a psychosocial study of male IDUs.

This longitudinal study examined the psychosocial risk and protective factors involved in condom use among 265 male IDUs. Subjects were individually interviewed at two points in time using a structured questionnaire, which included psychosocial measures and questions about drug use and condom use. Data were analyzed using Pearson correlations and hierarchical regression analyses. T1 condom use was the most powerful predictor of T2 condom use, with or without control on other variables. T1 family support for condom use, friends' support for condom use, adaptive coping with AIDS or the threat of AIDS, and planning to use condoms were significantly related to T2 condom use. Protective father factors enhanced the effects of other protective psychosocial factors, increasing T2 condom use. The results suggest several approaches for changing risk-taking sexual behavior in male IDUs: enhancing coping abilities, selecting peers who take fewer risks, and planning to use condoms.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Loss of 3-nitrotyrosine on exposure to hypochlorous acid: implications for the use of 3-nitrotyrosine as a bio-marker in vivo.

Peroxynitrite (ONOO-) is a reactive nitrogen species which in vivo is often assessed by the measurement of free or protein bound 3-nitrotyrosine. Indeed, 3-nitrotyrosine has been detected in many human diseases. However, at sites of inflammation there is also production of the powerful oxidant hypochlorous acid (HOCl) formed by the enzyme myeloperoxidase. Low concentrations of HOCl (<30 microM) caused significant and rapid loss (<10 minutes) of free and protein bound 3-nitrotyrosine. In contrast, no loss of 3-nitrotyrosine was observed with hydrogen peroxide, hydroxyl radical, or superoxide generating systems. Therefore, under conditions where there is concomitant peroxynitrite and hypochlorous acid formation, such as at sites of chronic inflammation, it is possible that HOCl removes 3-nitrotyrosine. This may have implications when assessing the role of reactive nitrogen species in disease conditions and could account for some of the discrepancies reported between 3-nitrotyrosine levels in tissues.

Biomarkers↗
PubMed1999

Hypochlorous acid-induced DNA base modification: potentiation by nitrite: biomarkers of DNA damage by reactive oxygen species.

Chronic inflammation results in increased nitric oxide formation and nitrite (NO-2) accumulation. Activated phagocytes release myeloperoxidase generating the cytotoxic agent hypochlorous acid (HOCl). Reaction of HOCl with NO-2 results in the formation of nitryl chloride (NO2Cl), a potent oxidising, nitrating and chlorinating species. Exposure of DNA to NO-2 alone (up to 250 microM) at pH 7.4 did not induce oxidative DNA base damage. However, incubation of DNA with NO-2 in the presence of HOCl led to increases in thymine glycol, 5-hydroxyhydantoin, 8-hydroxyadenine and 5-chlorouracil to levels higher than those achieved by HOCl alone. No significant increases in 8-hydroxyguanine, xanthine, hypoxanthine, 2-hydroxyadenine, FAPy guanine, FAPy adenine and 8-chloroadenine were observed. HOCl-induced depletion of FAPy guanine and 8-hydroxyguanine was reduced in the presence of NO-2. Modification of DNA by HOCl/NO-2 (presumably generating NO2Cl) produces a pattern of DNA base damage products in isolated DNA that is similar to the pattern produced by HOCl but not other reactive species.

Animals↗
PubMed1999

The role of parents in protecting Colombian adolescents from delinquency and marijuana use.

OBJECTIVES: To identify general and differentiating risk and protective factors from domains of culture and ecology, peer, family, and personality, related to adolescent delinquency and marijuana use, and to study the protective role of the parent-child mutual attachment in offsetting cultural and ecological risk factors, leading to less delinquency and marijuana use. DESIGN: Cross-sectional analyses of interview data collected in Colombia. PARTICIPANTS: A total of 2837 Colombian adolescents, 12 to 17 years of age. SETTING: Adolescents were interviewed in their homes. MAIN MEASURES: Independent variables included measures from 4 domains: culture and ecology, peer, family, and personality. The dependent variables were delinquency and marijuana use. RESULTS: Several risk factors, such as tolerance of deviance and sensation seeking, were similarly related to both delinquency and marijuana use, suggesting that a common cause underlies the propensity to engage in different deviant behaviors. Some risk factors were more involved in delinquency and other risk factors were more highly related to the adolescent's marijuana use. Finally, when violence is endemic and illegal drugs are readily available, a close parent-child bond was capable of mitigating these risk factors, leading to less marijuana use and delinquency. CONCLUSIONS: The findings have implications for public health policy related to interventions in countries in which violence and drug use are prevalent. The results point to interventional procedures aimed at adolescents vulnerable to marijuana use and delinquency as well as efforts aimed at specific vulnerabilities in these areas. For example, reducing the risk factors and enhancing the protective factors for marijuana use and delinquency may result in less adolescent marijuana use and delinquency.

Adolescent↗
PubMed1999

Modulation of peroxynitrite- and hypochlorous acid-induced inactivation of alpha1-antiproteinase by mercaptoethylguanidine.

1. Peroxynitrite is a cytotoxic species that can be formed, among other mechanisms, by the rapid reaction of superoxide with nitric oxide. Peroxynitrite formation has been implicated in a wide range of neurodegenerative and chronic inflammatory diseases, as has the formation of hypochlorous acid by myeloperoxidase. 2. There is considerable interest in the development of peroxynitrite scavengers as therapeutic agents. The thiol compound mercaptoethylguanidine has been suggested to fulfil this role since it has recently been shown to be not only a potent inhibitor of inducible nitric oxide synthase but also a scavenger of peroxynitrite. Indeed, it has been shown to be protective in some experimental models of circulatory shock and inflammation at plasma levels in the approximate range 100-300 microM. 3. One protein inactivated by peroxynitrite is the major inhibitor of serine proteinases in human body fluids, alpha1-antiproteinase. At high (250-1000 microM) concentrations, mercaptoethylguanidine was found to be effective in preventing peroxynitrite-mediated tyrosine nitration and alpha1-AP inactivation. 4. By contrast, lower concentrations of mercaptoethylguanidine (1-60 microM) enhanced the inactivation of alpha1-antiproteinase by peroxynitrite. 5. At all concentrations tested (1-1000 microM), mercaptoethylguanidine decreased the inactivation of alpha1-antiproteinase by hypochlorous acid. 6. We suggest that products of reaction of mercaptoethylguanidine with peroxynitrite or peroxynitrite-derived products could cause damage to alpha1-antiproteinase, and possibly other proteins in vivo, whereas scavenging of hypochlorous acid by mercaptoethylguanidine could contribute to its anti-inflammatory action in vivo.

Dose-Response Relationship, Drug↗
PubMed1999

Nitric oxide and peroxynitrite. The ugly, the uglier and the not so good: a personal view of recent controversies.

Nitric oxide, a gaseous free radical, is poorly reactive with most biomolecules but highly reactive with other free radicals. Its ability to scavenge peroxyl and other damaging radicals may make it an important antioxidant in vivo, particularly in the cardiovascular system, although this ability has been somewhat eclipsed in the literature by a focus on the toxicity of peroxynitrite, generated by reaction of O2*- with NO* (or of NO- with O2). On balance, experimental and theoretical data support the view that ONOO- can lead to hydroxyl radical (OH*) generation at pH 7.4, but it seems unlikely that OH* contributes much to the cytotoxicity of ONOO-. The cytotoxicity of ONOO- may have been over-emphasized: its formation and rapid reaction with antioxidants may provide a mechanism of using NO* to dispose of excess O2*-, or even of using O2*- to dispose of excess NO*, in order to maintain the correct balance between these radicals in vivo. Injection or instillation of "bolus" ONOO- into animals has produced tissue injury, however, although more experiments generating ONOO- at steady rates in vivo are required. The presence of 3-nitrotyrosine in tissues is still frequently taken as evidence of ONOO- generation in vivo, but abundant evidence now exists to support the view that it is a biomarker of several "reactive nitrogen species". Another under-addressed problem is the reliability of assays used to detect and measure 3-nitrotyrosine in tissues and body fluids: immunostaining results vary between laboratories and simple HPLC methods are susceptible to artefacts. Exposure of biological material to low pH (e.g. during acidic hydrolysis to liberate nitrotyrosine from proteins) or to H2O2 might cause artefactual generation of nitrotyrosine from NO2- in the samples. This may be the origin of some of the very large values for tissue nitrotyrosine levels quoted in the literature. Nitrous acid causes not only tyrosine nitration but also DNA base deamination at low pH: these events are relevant to the human stomach since saliva and many foods are rich in nitrite. Several plant phenolics inhibit nitration and deamination in vitro, an effect that could conceivably contribute to their protective effects against gastric cancer development.

Animals↗
PubMed1999

The risks for late adolescence of early adolescent marijuana use.

OBJECTIVES: The purpose of this study was to assess the relation of early adolescent marijuana use to late adolescent problem behaviors, drug-related attitudes, drug problems, and sibling and peer problem behavior. METHODS: African American (n = 627) and Puerto Rican (n = 555) youths completed questionnaires in their classrooms initially and were individually interviewed 5 years later. Logistic regression analysis estimated increases in the risk of behaviors or attitudes in late adolescence associated with more frequent marijuana use in early adolescence. RESULTS: Early adolescent marijuana use increased the risk in late adolescence of not graduating from high school; delinquency; having multiple sexual partners; not always using condoms; perceiving drugs as not harmful; having problems with cigarettes, alcohol, and marijuana; and having more friends who exhibit deviant behavior. These relations were maintained with controls for age, sex, ethnicity, and, when available, earlier psychosocial measures. CONCLUSIONS: Early adolescent marijuana use is related to later adolescent problems that limit the acquisition of skills necessary for employment and heighten the risks of contracting HIV and abusing legal and illegal substances. Hence, assessments of and treatments for adolescent marijuana use need to be incorporated in clinical practice.

Adolescent↗
PubMed1999

Transmission of risk factors across three generations.

The present study examined the association between the parent-grandmother relationship, the parenting of toddlers, and toddlers' anger. Parent-grandmother relations were assessed when the parents were adolescents. Patient-toddler relations were examined when the toddlers were two years of age. The sample consists of 185 2-yr-old toddlers, one of the parents of each toddler, and the corresponding grandmother of each toddler. The findings support our hypothesis that there would be an indirect effect of the grandmothers' personalities and child-rearing practices on their grandchildren through the influence of the grandmothers on the parents. The influence of both the grandmothers' and the parents' smoking behaviors on the toddlers' anger was mediated by their child-rearing practices. The significance of the findings from a multigenerational study are discussed with reference to incorporating them into prevention programs. The findings are consistent with the notion of the intergenerational transmission of risk factors--from grandparents to parents to toddlers.

Adolescent↗
PubMed1999

Giant lipoma of the larynx: a case report and literature review.

Fewer than 15% of lipomas occur in the head and neck. To date, fewer than 100 cases of laryngeal lipoma have been reported in the literature. Typical clinical manifestations include dysphagia, dyspnea and hoarseness, as well as the presence of a smooth or pedunculated mass seen endoscopically and a low attenuation mass on computed tomography scan. Pathologic sections commonly reveal a tumor consisting of mature adipocytes, which is often encapsulated. Treatment of laryngeal lipoma varies from conservative total endoscopic removal to external surgical approaches. The following is a report of a single case of laryngeal lipoma, including pathologic and radiologic findings, as well as a review of the literature.

Humans↗