Biomedical subjects

M Whiteman

Publications and source records attributed to M Whiteman.

At least 37 records · Page 2Linked to original sources

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1997

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↗

PubMed1997

Antioxidant action of ergothioneine: assessment of its ability to scavenge peroxynitrite.

The superoxide radical (O.2-) and nitric oxide (NO.) combine very rapidly to form peroxynitrite (ONOO-), a reactive tissue damaging nitrogen species thought to be involved in the pathology of several chronic diseases. The natural product ergothioneine protects against the nitration of tyrosine and the inactivation of alpha 1-antiproteinase by ONOO-. Ergothioneine merits further investigation as a biological and therapeutic antioxidant agent.

Antioxidants↗

PubMed1997

Thiourea and dimethylthiourea inhibit peroxynitrite-dependent damage: nonspecificity as hydroxyl radical scavengers.

Thiourea and, more recently, dimethylthiourea, have been used as hydroxyl radical (OH.) scavengers in experiments both in vitro and in vivo. We show that both compounds can inhibit nitration of the amino acid tyrosine on addition of peroxynitrite, and also the inactivation of alpha1-antiproteinase by peroxynitrite. Hence, protective effects of (dimethyl) thiourea could be due to inhibition of peroxynitrite-dependent damage as well as to OH. scavenging, and these compounds must not be regarded as specific OH. scavengers.

Enzyme Inhibitors↗

PubMed1997

Antioxidant properties of S-adenosyl-L-methionine: a proposed addition to organ storage fluids.

Glutathione (GSH) depletion adversely affects the survival of organ grafts. Supplementation of commercial organ preservation solutions with GSH is complicated by the ease of oxidation of its thiol group and its ability to act as a pro-oxidant under certain conditions. Alternative sulphur-containing compounds such as S-adenosyl-L-methionine (SAM) can reduce ischaemia-reperfusion injury, possibly by acting as glutathione precursors, and are effective when added to preservation solutions. Although the antioxidant properties of GSH are known in some detail, there is little information on the ability of SAM to interact directly with reactive oxygen species (ROS) produced during ischaemia-reperfusion injury. This work compares the interaction of SAM and GSH with several ROS which may be formed during ischaemia-reperfusion. In a variety of lipid peroxidation systems, SAM and GSH had little effect except at high concentrations (5 mM) where they became pro-oxidant. Scavenging of O2.- by both species was slow. SAM was less effective than GSH at preventing damage by peroxynitrite or HOCl. In contrast, SAM was more effective than GSH in scavenging hydroxyl radicals (.OH) and in chelating iron ions to inhibit .OH generation. Unlike GSH, SAM did not stimulate .OH formation at low concentrations. The beneficial effects of SAM in preservation solutions could therefore include direct radical scavenging as well as acting as a precursor for intracellular GSH.

Antioxidants↗

PubMed1997

Hypochlorous acid-induced base modifications in isolated calf thymus DNA.

Exposure of calf thymus DNA to hypochlorous acid/hypochlorite leads to extensive DNA base modification. Large concentration-dependent increases in pyrimidine oxidation products [thymine glycol (cis/trans), 5-hydroxycytosine, 5-hydroxyuracil, 5-hydroxyhydantoin] but not purine oxidation products (8-hydroxyguanine, 2- and 8-hydroxyadenine, FAPy guanine, FAPy adenine) were observed at pH 7.4. In addition, large increases in 5-chlorouracil (probably formed from 5-chlorocytosine during sample preparation), a novel chlorinated base, were observed. Addition of HOCl to DNA already damaged by .OH generated by a mixture of ascorbate, copper(II) chloride, and hydrogen peroxide showed that hypochlorous acid led to a loss of 8-hydroxyguanine, 2- and 8-hydroxyadenine, FAPy guanine, FAPy adenine, and 5-hydroxycytosine in a concentration- and pH-dependent manner. Nevertheless, time course studies suggested that the formation of purine oxidation products in isolated DNA by hypochlorous acid was not a major oxidation pathway. If this pattern of damage, especially the production of 5-chlorocytosine, is unique to hypochlorous acid, it might act as a "fingerprint" of damage to DNA by HOCl.

Animals↗

PubMed1997

Effect of peroxynitrite on plasma extravasation, microvascular blood flow and nociception in the rat.

1. Peroxynitrite (ONOO-) is a cytotoxic species, formed by the reaction between nitric oxide and superoxide free radicals, that may be involved in inflammation. In this study we have investigated the effect of peroxynitrite on plasma extravasation and microvascular blood flow in the dorsal skin and on nociceptive responses in the hind paw of the rat. 2. Male Wistar rats were anaesthetized and their dorsal skin shaved. Plasma extravasation was measured by the extravascular accumulation of 125I-labelled albumin over 0-45 min and 0-240 min. Blood flow was measured by laser-Doppler flowmetry over 0-240 min. Studies in the hind paw were carried out in the conscious rat. Hind paw weight changes were determined by volume displacement and nociception by a mechanical hyperalgesia technique. 3. Intradermal (i.d.) peroxynitrite (100-200 nmol site-1) produced a significant (P < 0.01) dose-dependent increase in plasma extravasation in dorsal skin over 0-45 min which was not increased over 45-240 min. Plasma extravasation was significantly (P < 0.001) decreased in rats pretreated with the anti-inflammatory steroid dexamethasone (1 mg kg-1, i.v.; -180 min), but not modulated by treatment with the hydrogen peroxide deactivator catalase (2200 u site-1), or the superoxide scavenger superoxide dismutase (500 u site-1), effective doses of the tachykinin NK1 antagonist SR140333 (1 nmol site-1), the cyclo-oxygenase inhibitor indomethacin (358 mumol site-1), or combined pretreatment with mepyramine (histamine H1-receptor antagonist; 2.8 nmol site-1) and methysergide (5-HT antagonist; 1.9 nmol site-1). 4. Microvascular blood flow was significantly (P < 0.05) increased 30 and 120 min after i.d. peroxynitrite (100 nmol site-1) in dorsal skin and remained raised until the end of the recording period (240 min). The increase in blood flow was unaffected by dexamethasone (1 mg kg-1, i.v.; -180 min) or indomethacin (10 mg kg-1, s.c.; -30 min). 5. Hind paw volume was significantly (P < 0.001) increased 30 min after intraplantar peroxynitrite (87.5 and 175 nmol paw-1) and remained raised for the duration of the experiment (360 min). By comparison, nociception was not altered by intraplantar peroxynitrite. 6. These data indicate that peroxynitrite can cause an increase in both plasma extravasation and blood flow, suggesting that peroxynitrite could be of biological relevance to microvascular responses. These findings may be of importance in the pathology of inflammatory diseases in which peroxynitrite formation occurs.

Animals↗

PubMed1997

Scavenging of hydroxyl radicals but not of peroxynitrite by inhibitors and substrates of nitric oxide synthases.

1. The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) is widely used to study the role of NO. in physiological and pathological processes, including its role in the generation of the cytotoxic species peroxynitrite (ONOO-) and of reactive oxygen radicals such as hydroxyl (OH.). Often L-NAME is applied to tissues at mM concentrations. At such high concentrations, it might act as a free radical scavenger. A similar possibility might apply to the use of high levels of arginine to study the role of NO. in atherogenesis. 2. We therefore examined the rate of scavenging of OH. by L-NAME and found that L-NAME reacts more quickly with OH. than the established 'OH. scavenger' mannitol and the widely used 'OH. trap' salicylate. However, D-NAME can scavenge OH. at rates equal to L-NAME. Both L- and D-arginine were also good OH. scavengers, comparable in effectiveness to mannitol. 3. Neither L-NAME, D-NAME, L-arginine nor D-arginine was able to inhibit ONOO(-)-dependent nitration of tyrosine, suggesting that they are unlikely to be scavengers of ONOO(-)-derived nitrating species. 4. Neither L-NAME, D-NAME, L-arginine nor D-arginine was able to inhibit the inactivation of alpha 1-antiproteinase by ONOO-, suggesting that they cannot prevent direct oxidations by peroxynitrite. 5. We conclude that L-NAME has sufficient activity as an OH. scavenger to confound certain pharmacological experiments. However, this explanation of its biological effects can be ruled out if control experiments show that D-NAME has no effect and that L-arginine (also a free radical scavenger) antagonizes the action of L-NAME.

Dose-Response Relationship, Drug↗

PubMed1997

Drug use and delinquency: shared and unshared risk factors in African American and Puerto Rican adolescents.

The shared and unshared psychosocial risk factors related to stage of drug use and delinquency were examined. The sample consisted of 655 African American and 600 Puerto Rican male and female adolescents. Net regression analysis was used to analyze the data. The results showed that adolescent stage of drug use and delinquency reflect shared and unshared risk factors. The magnitude of the risk factors for adolescent delinquency was greater than for stage of drug use. The findings support a socialization hypothesis (from parent, to personality, to behavior), and the data were congruent with a dispositional model (from child, to parent or peer, to behavior).

Adolescent↗

PubMed1997

Cigarette smoking in young adults: childhood and adolescent personality, familial, and peer antecedents.

Three models (independent, interdependent, and mediational) were hypothesized in this study, to examine the interrelation of personality, family, and peer determinants and their effects on tobacco use by young adults. Mothers were first interviewed about their children when they were between the ages of 1 and 10 years old. Three subsequent interviews were conducted with the children when they reached adolescence and young adulthood. Results show support for the mediational model. In accordance with family interactional framework conceptions, there was a sequence in patterning: from parenting during early adolescence; to personality and peer factors, extending to smoking in late adolescence; and culminating in smoking in adulthood. With a developmental approach, a number of psychosocial measures were related in both younger and older children. Nevertheless, some interesting developmental differences emerged. The findings suggest at least four possible targets for therapeutic or preventive intervention: the parent, the child, the adolescent, and the peer group.

Adolescent↗

PubMed1997

Prevention of peroxynitrite-dependent tyrosine nitration and inactivation of alpha1-antiproteinase by antibiotics.

Peroxynitrite, formed by reaction of superoxide and nitric oxide, appears to be an important tissue damaging species generated at sites of inflammation. In this paper, we compare the abilities of several antibiotics to protect against peroxynitrite-dependent inactivation of alpha1-antiproteinase, and to inhibit tyrosine nitration by peroxynitrite, in vitro. Tetracycline, minocycline, doxycycline, rifamycin and rifampicin were highly protective in both assay systems, whereas several other antibiotics tested were not. The possibility that antibiotics could affect tissue injury at sites of inflammation by scavenging peroxynitrite is discussed.

Anti-Bacterial Agents↗

PubMed1997

Peroxynitrite-dependent aromatic hydroxylation and nitration of salicylate and phenylalanine. Is hydroxyl radical involved?

There is considerable dispute about whether the hydroxylating ability of peroxynitrite (ONOO-)- derived species involves hydroxyl radicals (OH.). This was investigated by using salicylate and phenylalanine, attack of OH. upon which leads to the formation of 2,3- and 2,5-dihydroxybenzoates, and o- m- and p- tyrosines respectively. On addition of ONOO- to salicylate, characteristic products of hydroxylation (and nitration) were observed in decreasing amounts with rise in pH, although added products of hydroxylation of salicylate were not recovered quantitatively at pH 8.5, suggesting further oxidation of these products and underestimating of hydroxylation at alkaline pH. Hydroxylation products decreased in the presence of several OH. scavengers, especially formate, to extents similar to those obtained when hydroxylation was achieved by a mixture of iron salts, H2O2 and ascorbate. However, OH. scavengers also inhibited formation of salicylate nitration products. Ortho, p- and m-tyrosines as well as nitration products were also observed when ONOO- was added to phenylalanine. The amount of these products again decreased at high pH and were decreased by addition of OH. scavengers. We conclude that although comparison with Fenton systems suggests OH. formation, simple homolytic fission of peroxynitrous acid (ONOOH) to OH. and NO2. would not explain why OH. scavengers inhibit formation of nitration products.

Chromatography, High Pressure Liquid↗

PubMed1997

Coping with AIDS. A longitudinal study.

The goals of this longitudinal, prospective study were to 1) examine coping strategies of HIV-positive (HIV+) and HIV-negative (HIV-) injecting drug users; 2) study the relationship of earlier social support to later coping in HIV+ men; and 3) examine the effects of earlier coping strategies on later psychosocial function. The authors studied 287 men given a structured questionnaire at two points in time. HIV+ subjects scored higher than HIV- subjects on measures of AIDS-related adaptive coping (social support) and AIDS-related maladaptive coping (aggression), but not on general coping. General coping was not specifically AIDS-related, but was correlated positively with adaptive coping and negatively with maladaptive coping. These results suggest that earlier general coping is related to the later avoidance of maladaptive coping, and they have specific implications for teaching preventive strategies. AIDS-related adaptive or maladaptive coping techniques may be used simultaneously, and coping behavior may change over time. Earlier social support is related positively to aspects of later coping in HIV+ men.

Acquired Immunodeficiency Syndrome↗