PubMed HealthSearch

Biomedical subjects

M Whiteman

Publications and source records attributed to M Whiteman.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

Consequences of adolescent marijuana use: incompatibility with the assumption of adult roles.

This longitudinal study is an examination of the relationship between marijuana use and the assumption of adult roles, as well as the relationship between assuming adult roles and the likelihood of later marijuana use. Data were collected at 5 points in time from childhood through early adulthood (late 20s) by means of a structured questionnaire. Participants' marijuana use and the assumption of adult roles, including employment, marriage, parenthood, and living arrangements, were measured, and the data were analyzed with logistic regression analyses. A history of marijuana use was associated with an increased risk of adopting more unconventional adult roles, such as postponement of marriage, having a child out of wedlock, and unemployment. These results suggest that frequent prior marijuana use may adversely affect one's ability to successfully assume conventional adult roles. Furthermore, controlling for earlier marijuana use, marriage during early adulthood significantly decreased the risk of later marijuana use.

Adolescent

Coping among HIV negative and HIV positive female injection drug users.

The study examined the psychosocial determinants of coping ability in a cohort of 249 HIV positive and HIV negative female injection drug users (IDUs), using a cross-sectional retrospective design. Information collected using a structured questionnaire included data on psychosocial risk and protective factors in the personality, family, and peer domains, HIV status, and coping ability. Coping ability was associated with conventionality, greater control of emotions, less psychopathology, and family cohesion in both HIV positive and HIV negative subjects. The psychosocial factors affected coping in HIV positive and HIV negative IDUs via two different mediational models. The interactional findings supported the influence of risk/protective interactions in both groups. The findings demonstrate the impact of the interplay between personality factors and external support on coping ability in female IDUs.

Adaptation, Psychological

Coping strategies of HIV-positive and HIV-negative female injection drug users: a longitudinal study.

This study longitudinally examined the psychosocial correlates of coping strategies among 165 HIV positive and 179 HIV negative female injection drug users (IDUs). Participants were interviewed twice using a structured questionnaire, with a 6-month interval between interviews. The questionnaire included psychosocial measures as well as measures of general coping and specific HIV-related coping. Data were analyzed using logistic regression analyses. The findings indicated that favorable factors in the psychosocial domains at Time 1 were significantly associated with an increased likelihood at Time 2 of the use of general coping and specific adaptive coping strategies, such as problem solving and seeking social support, and with a decreased likelihood at Time 2 of the use of maladaptive coping strategies, such as aggression and the use of illicit drugs. These findings highlight particular areas of psychosocial functioning that can be targeted by intervention programs to promote adaptive coping and minimize maladaptive coping among HIV positive and HIV negative female IDUs.

Adaptation, Psychological

Older sibling correlates of younger sibling drug use in the context of parent-child relations.

The purpose of this study was to examine older brother correlates of younger brother drug use in the context of parental influences and younger brother personality. The sample consisted of 278 White male college students and their oldest brothers, who volunteered to answer self-administered questionnaires. Results indicated that 3 domains of influence each had an independent impact on younger brother drug use: (a) parent-younger brother relationships and parent drug use, (b) older brother-younger brother relationships and older brother drug use, and (c) younger brother personality. Modeling of nondrug use and a strong attachment relationship in the parent-younger brother and sibling dyads, as well as younger sibling traits of conventionality, had strong links to low younger brother drug use. Our findings highlight the importance of modeling and mutual parent-child attachment relationships as well as sibling relationships as they relate to the possible etiology of drug use.

Adult

Similar and different precursors to drug use and delinquency among African Americans and Puerto Ricans.

Correlational and net regression techniques were used to examine the commonalities and differences in risks for later drug use and delinquency among African American and Puerto Rican adolescents. Eight-eight percent of the risks were significantly related to both problem behaviors. Within the personality, family, peer, ecology, and acculturation domains, many risks independently contributed to the prediction of each problem. Only three risks had a significantly stronger relationship to one of the problem behaviors than to the other. Finding so many common predictors supports a general dimension of problem behavior and highlights the psychosocial risks for drug use and delinquency. The commonalities suggest that interventions targeting these adolescent risks might reduce both problem behaviors.

Acculturation

Progressive multifocal leukoencephalopathy in patients with HIV infection.

Progressive multifocal leukoencephalopathy (PML), a formerly rare disease, is estimated to occur in up to 5% of all patients with AIDS. The high prevalence of PML in AIDS patients currently enables a comprehensive evaluation of this disorder. We evaluated the clinical and radiographic features of PML in a large cohort of AIDS patients identified by retrospective chart review from 1981 to 1994. Two hundred and five patients were diagnosed with PML of which 154 met the inclusion criteria. Seventy-two (47%) were pathologically confirmed and the remaining 82 (53%) met clinical and radiographic criteria. There was a 12-fold increase in the frequency of PML between 1981-1984 and 1991-1994. PML affected 136 men and 18 women with AIDS. Eighty-four percent of cases were 20-50 years old (range 5 to 68 years). The most common AIDS risk factors were homosexuality (57%) among men and heterosexual transmission (28%) and intravenous drug abuse (28%) among women. In 27% of patients, PML heralded AIDS. Common manifestations included weakness, gait abnormalities, speech disturbance, cognitive disorders, headache, and visual impairment. The CD4 lymphocyte counts exceeded 200 cells in 11% at the time of presentation. Involvement of posterior fossa structures was evident in 48% of cranial magnetic resonance imaging (MRI) studies, but in only 11% of computed tomographies (CT) of the brain. Contrast enhancement, typically faint and peripheral, was seen in 10% of CT scans and 15% of MRIs. The median survival was 6 months and survival exceeded 1 year in 9%. PML is no longer a rare disease. It often heralds AIDS and may occur in the absence of significant decline in CD4 lymphocytes. Survival is generally poor, although prolonged survival beyond 1 year is not unusual.

Acquired Immunodeficiency Syndrome

Psychosocial risk and protective factors for condom use among female injection drug users.

The authors examined the influences of domains of psychosocial risk and protective factors on male-partner condom use in a cobort of 209 female HIV-positive (HIV+) and HIV-negative (HIV-) injection drug users (IDUs) by use of a cross-sectional, retrospective design. Information collected from a structured questionnaire included data on psychosocial risk and protective factors in the personality, family, and peer domains; HIV status; and condom use. Among HIV+ IDUs, personality risk factors (e.g., unconventionality), family (e.g., low maternal identification), and peer factors were related to less male-partner condom use. Resources and condom availability were associated with greater male condom use with both HIV+ and HIV- IDUs. The psychosocial domains affected male condom use with both HIV+ and HIV- female IDU patients via two different mediational models. The findings suggest the need to use specific psychosocial interventions for risky sexual behavior among HIV+ and HIV- female IDUs.

Adolescent

Pathways to marijuana use among adolescents: cultural/ecological, family, peer, and personality influences.

OBJECTIVE: To examine the linkages, cultural/ecological factors, and major psychosocial risk factors as they relate to drug use in a sample from Colombia, South America. METHOD: The participants were 1.687 adolescents living in mixed urban-rural communities in Colombia, South America. An individual interview was administered to youths in their homes by Colombian interviewers. The scales used were based on item intercorrelations grouped into the following risk categories: (1) adolescent personality, (2) family traits, (3) peer factors, and (4) cultural/ecological variables. RESULTS: Pearson correlations were computed for each variable and the frequency of marijuana use. Results show that each of the domains was related to adolescent marijuana use, with some notable gender differences. As regards the interrelation of domains, a mediational model was operative. CONCLUSIONS: Findings support a family interactional theory. The domains of family, personality, and peer factors had a direct effect on the adolescents' marijuana use. Implications for prevention are also addressed.

Adolescent

A three-generation study: intergenerational continuities and discontinuities and their impact on the toddler's anger.

One hundred fifteen 2-year-old toddlers, one of the parents of each toddler, and the corresponding grandmother of each toddler were studied to determine the influence of the grandmother and the parent on the toddler's behavior. Findings indicated that the grandmother's parenting skills have an effect on the grandchild's anger via two pathways. More specifically, the grandmother's child-rearing techniques are mediated by the parent's personality traits, which, in turn, are associated with the parent's child-rearing practices and, ultimately, the grandchild's anger. The second pathway through which the grandmother's child-rearing is related to the grandchild's behavior involves the parent's imitation of the grandmother's parenting skills, which, in turn, are correlated with the toddler's behavior.

Anger

Mutual attachment, personality, and drug use: pathways from childhood to young adulthood.

Young adult drug use stemming from childhood aggression, the parent-child mutual attachment relationship, and the effect of unconventionality were studied. Youngsters and their mothers were interviewed when the former were early adolescents, late adolescents, and young adults. Additional data were collected from the mothers when their youngsters were children. The analysis was conducted on youngsters who had complete data at all 4 points in time. The findings were in accord with the family interactional model; that is, the parent-child mutual attachment relationship affects unconventionality in the youngster, which, in turn, affects young adult drug use. The results indicate that the parent-child mutual attachment relationship does so through (a) the stability of the attachment relationship from childhood to young adulthood, (b) the stability of unconventional personality and behavioral attributes from early adolescence to young adulthood, and (c) the stability of drug use from early adolescence to young adulthood. The findings imply that (a) early intervention with respect to aggression, (b) interventions that focus on strengthening the parent-child bond and conventional behavior, and (c) interventions aimed at early drug use should be most effective in reducing young adult drug use.

Adolescent

Thiols and disulphides can aggravate peroxynitrite-dependent inactivation of alpha1-antiproteinase.

Peroxynitrite (ONOO-) is a cytotoxic species formed in vivo. There is considerable interest in the development of ONOO- 'scavengers' as therapeutic agents; several thiols have been suggested to fulfil this role. One protein inactivated by ONOO- is alpha1-antiproteinase (alpha1AP), the major inhibitor of serine proteinases in human body fluids. At low thiol:ONOO- concentration ratios, several thiols (captopril, penicillamine, cysteine, cystine and penicillamine disulphide) aggravated inactivation of alpha1AP by ONOO- , whereas GSH, GSSG, homocysteine, ergothioneine, N-acetylcysteine, lipoate and dihydrolipoate did not. We suggest that sulphur-containing radicals are produced by reaction of certain thiols/disulphides with ONOO- or ONOO- -derived products and could mediate biological damage, including inactivation of alpha1AP. This must be considered in attempts to use thiols as 'peroxynitrite scavengers'.

Disulfides