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Biomedical subjects

A Falek

Publications and source records attributed to A Falek.

At least 19 recordsLinked to original sources
PubMed1992

A comparison study of treated and untreated pregnant and postpartum cocaine-abusing women.

The purpose of this study was to determine whether untreated pregnant and recently post-partum cocaine-abusing women could be differentiated from women who enrolled in drug treatment programs. The experimental sample was selected from women referred to the Georgia Addiction, Pregnancy, and Parenting Project, an intervention program for pregnant and postpartum addicted women, between January 1987 and January 1988 (n = 45). The comparison group was randomly selected from women who were admitted to two (2) day treatment programs during the same time period (n = 50). Groups were compared using the Addiction Severity Index (ASI) and the Psychiatric Symptom Checklist-90 (SCL-90). Results indicated that untreated women were less impaired socially and exhibited fewer symptoms of psychiatric distress. These findings confirm the commonly held belief that the severity of psychosocial distress may be an important motivating factor in the decision to enter drug treatment. Alternatively, the lack of gender-sensitive program components, such as childcare, and the social stigma attached to drug use in pregnancy may also account for the reluctance of pregnant and post-partum mothers to seek drug treatment. Implications for the development of intervention and treatment programs for women are discussed.

Adult↗
PubMed1991

The use of nonneuronal cells as an in vitro model system for studying the genetic component of cellular response to opiates and other drugs of abuse.

Nonneuronal cells, such as the human T lymphocyte, react directly with opiates in vitro causing significant alterations in the metabolism of these cells. Morphine and cocaine, for example, can modulate the repair of DNA damage caused by ultraviolet light (UVC)--morphine in the negative direction and cocaine in the positive. The mechanism by which these drugs cause these metabolic changes is not yet known, but a simple receptor mechanism such as is found in the central nervous system (CNS) can not be demonstrated. Binding studies using lymphocyte membrane preparations or whole cells do not support the premise that T lymphocytes have opiate binding sites with specificities comparable to those identified in the CNS--the mu, delta and kappa receptors. Even without knowing the mechanism for the opiate-induced metabolic changes, the alterations can be used as the basis for a test of the genetics of opiate metabolism. If the interindividual variation in the opiate-induced repair response is greater than the intraindividual variation as assessed by repeated measures on the same subject, it may be possible to utilize this assay in the classic sorts of family or twin studies to determine the genetic component of the response to opiates.

Cell Line↗
PubMed1990

Enhanced assays detect increased chromosome damage and sister-chromatid exchanges in heroin addicts.

To refine previous studies of chromosome damage (CD) and sister-chromatid exchanges (SCE) in heroin addicts, we applied new methods developed in our laboratory to enhance detection of the cytogenetic effects of low-level radiation exposure in hospital workers. For CD analysis, we applied our thymidine-fluorodeoxyuridine-caffeine (TFC) enhancement procedure in which cells at setup receive 1 x 10(-7) M fluorodeoxyuridine to inhibit thymidylate synthetase and 4 X 10(-5) M thymidine to satisfy the induced requirement, and then in G2 receive 2.2 mM caffeine to modulate DNA repair. For SCE enhancement, caffeine treatment was initiated in G1 at 19 h before harvest. Using both standard and enhanced procedures for CD and SCE analysis, blood samples were evaluated from 20 street heroin addicts and 22 controls. Standard 2-day CD and 3-day SCE assays showed small, insignificant genotoxic increases in addicts while the enhanced CD and SCE assays showed highly significant increases. Most CD events were in the form of chromatid and chromosome breaks. There were no rings and only a few dicentrics were observed in the TFC-enhanced cultures. Although quadriradials are rare, 10 were found in addict TFC-cultures and 3 in control TFC-cultures. With the standard CD assay, the mean number of chromosome breaks per 100 cells was 0.727 for controls and 1.056 for addicts (not significant). With the TFC-enhanced assay, the same measure showed 1.483 chromosome breaks for controls and 5.143 for addicts (highly significant, ANOVA: p less than 0.0001). A highly significant difference was also observed for chromatid-type damage with the TFC-enhanced assay (chromatid breaks per 100 cells: 16.793 for controls; 48.191 for addicts). The SCE data also showed significant differences with the enhanced assay. Scoring 25 cells/condition, standard SCE cultures showed 10.892 SCE/cell for controls and 11.732 SCE/cell for addicts (not significant). With CAF enhancement there were 13.08 SCE/cell for controls and 17.05 SCE/cell for addicts (ANOVA: p less than 0.008). These findings indicate that detection of CD and SCE effects can be significantly enhanced by the use of these new procedures. The finding of greatly increased chromatid damage in the addicts with the TFC procedure suggests that at least part of the CD detected occurred in vitro and is not a product of prior in vivo damage. Therefore exposure to this drug and perhaps other environmental agents may not only leave a residue of DNA or chromosome damage but may also induce a sensitivity to further genotoxic damage that is revealed by using the enhanced procedures.

Analysis of Variance↗
PubMed1990

Opiate binding sites on cells of the immune system.

Naloxone binding to T lymphocytes seems to occur both at the outer cell surface and in the interior of the cell. The binding sites on the outer membrane appear from previous work to be of low affinity and to be displaced by morphine only at very high concentrations. Permeable cells seem to express both high and low affinity binding sites in their interiors. Morphine readily displaces naloxone from this high affinity site, suggesting that this site may be the long sought after morphine receptor responsible for morphine's naloxone reversible actions on the human T lymphocyte. Do these results suggest that the opiates need to enter the lymphocyte before finding a receptive binding site to initiate their biological activities? Not necessarily. In isolating the lymphocytes, the surface opiate binding sites may be lost because of the exhaustive washing procedures needed for cell purification. The internal receptors may just represent new receptors on their way to the cell surface or used receptors remaining after endocytosis. Or they may indeed represent the true site of action of the opiates on the lymphocyte. Fractionation experiments are currently underway to distinguish between these possibilities.

Animals↗
PubMed1988

Cytofluorometric analyses of human T cell CD2/CD4 inter-molecular interactions.

Incubation of human T lymphocytes with saturating concentrations of combinations of certain anti-CD2 and -CD4 mAb results in reciprocal down-regulation of the cell surface density expression of the respective CD molecules. Such reciprocal down-regulation occurs at 0 degrees C in the presence of sodium azide and appears selective for CD2 and CD4 molecules because mAb identifying various other CD T cell surface molecules (anti-Leu2a, -OK-CLL, -W6/32, -beta 2-microglobulin, -4B4) do not modulate CD2 or CD4 R density, and because anti-CD2 mAb (anti-OKT11 and -D66 clone-1) do not alter CD8 R density (anti-OKT8, -Leu2a) and vice versa. Down-regulation of CD2 by mAb specific to CD4 is epitope-specific but does not vary on the basis of the antibody isotype used. The anti-CD4 mAb, Leu3a, was the strongest CD2 down-regulator examined followed by OKT4F. mAb specific to other CD4 epitopes (B, C, D, and E) caused only slight down-regulation of CD2 expression whereas anti-OKT4 and -OKT4A mAb had no significant regulatory effect. Also, mAb specific to the 9.6 (anti-OKT11) and D66 (anti-D66 clone 1) epitopes of the CD2 molecule down-regulated CD4 density detectable with Leu3a, OKT4, and OKT4A anti-CD4 mAb. Down-regulation of CD2 by anti-CD4 mAb also occurred with the transformed T cell line, KE-37, which demonstrates that such effects can occur without mononuclear phagocytic accessory cells. From these data it can be concluded that important T cell immunoregulatory signals may be transmitted intramembranally between CD2 and CD4 glycoproteins.

Adult↗
PubMed1988

Comparative effects of morphine on leukocytic antigenic markers of monkeys and humans.

Knowing the in vitro effects of morphine on monkey leukocytes would be helpful in extending the utility of a monkey model for psychoneuroimmunological investigations. Morphine effects on T11, Leu2a, and Leu3a antigenic markers on leukocytes from rhesus monkeys and humans were assessed by using single- and two-color cytofluorometric analyses. Kinetics of expression of these markers was determined after modulation of the original complement of T11 markers from the surface of T11(+) cells. Percentages of leukocytes detectable by directly staining these markers before modulation were within the expected range for monkey and human cells. Also, as expected, T11 modulation reduced the percentages of cells expressing T11. This reduction was particularly obvious for T11 in the single-color analyses, with reductions being greater for monkey than human cells. Furthermore, in the single-color analyses, the effects of morphine on kinetics of T11 expression were quite similar for both human and monkey cells. In the two-color analyses, the simultaneous expression of T11 and Leu3a markers was uniform for both monkey and human cells. The effects of morphine on kinetics of expression of these markers varied only slightly between species. On the other hand, the distribution of Leu2a on T11 cells was markedly different for monkey and human T-cells. Whereas all human Leu2a(+) cells expressed similar numbers of T11 receptors, monkey cells with high-density Leu2a expressed fewer T11 markers than those with low-density Leu2a. The effects of morphine on kinetics of Leu2a and T11 expression were at obvious variance between species.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Huntington disease in Georgia: age at onset.

Age at onset of motor symptoms was collected on 611 persons affected with Huntington disease (HD) among 3,201 persons "at risk" in 108 kindreds. Life-table estimates correcting for truncated intervals of observation (censoring) produced a median age at onset 5 years older than the observed mean. Risk estimates of HD onset for persons at risk, as calculated by life-table methods, were significantly higher for older ages than were estimates based on the observed distribution of onsets. Age-specific incidence was found to be highest at age 35-64 years, a considerably older age interval than suggested by previous estimates. The offspring of affected males had significantly younger onset than did offspring of affected females, and a trend suggesting and excess of paternal descent among juvenile-onset cases was present. Life-table analysis is contrasted with analyses of (a) the observed distribution of age at onset and (b) remote cohorts age 63 or older at the time of data collection. The implications for risk prediction, genetic counseling, and genetic analysis of HD are discussed.

Adult↗
PubMed1987

Binding of naloxone to human T lymphocytes.

Purified T lymphocytes have a specific binding site for naloxone, the opiate antagonist. The KD for the site was 50.6 +/- 2.4 nM, while the Hill coefficient (n) was 1.67 +/- 0.16, indicating a degree of positive cooperativity of ligand binding. The bound naloxone was partially displaceable by various opiate agonists including morphine (56%), beta-endorphin (61%), met5- and leu5-enkephalin (40% each), [D-ala2, D-leu5]-enkephalin (78%) and [D-ala2, D-leu5]-enkephalinamide (66%). Virtually all of the binding capacity was recovered in the particulate membrane fraction after sonic lysis of the cells. There was great interindividual variability in Bmax between samples, suggesting a possible mechanistic basis for the variability in drug action seen between different individuals.

Binding, Competitive↗
PubMed1987

Psychological impact of the development of a presymptomatic test for Huntington's disease.

For the first time, a genetic probe can provide individuals at risk for Huntington's disease (HD) with diagnostic information regarding this progressive genetic disorder before symptoms are exhibited. This article investigates the effects of such a technology on the at-risk HD population. At-risk HD individuals were informed about the genetic probe, and their level of anxiety was assessed. A group conference format was an effective means of providing information regarding the HD probe to a large number of at-risk families. Findings from the measure of anxiety demonstrate that the at-risk HD population is no different from a normative population or from an at-risk HD population unfamiliar with the new technology.

Anger↗
PubMed1987

Prenatal alcohol exposure and infant behavior: immediate effects and implications for later development.

Infants exposed to alcohol prenatally, even when they do not suffer from fetal alcohol syndrome (FAS), may be at high risk for many of the negative outcomes typically found among children of alcoholics including hyperactivity and other behavioral and learning problems. A series of studies are described designed to investigate the incidence and persistence of central nervous system (CNS) related behavioral alterations in three groups of infants born to low SES black women: (1) those who never drank in pregnancy; (2) those who drank at an average of 12 ounces of absolute alcohol (AA) per week throughout pregnancy; and (3) those who drank an equivalent amount but stopped by the second trimester of pregnancy. Only healthy, full-term infants were examined for the physical dysmorphic features associated with FAS and for behavioral alterations that could be assessed using the Brazelton Neonatal Behavioral Assessment Scale. One hundred and three neonates were examined at three days; those who had been exposed to alcohol were found to be less optimal in neurobehavioral responses. Infants whose mothers continued to drink were significantly lower on their orientation toward auditory and visual stimuli, motor performance, and autonomic regulation than the nonexposed infants. Although a second study found that some of these effects were related to neonatal withdrawal syndrome, a follow-up to 30 days of age in a subsample of the original group found that there were persistent behavioral alterations. Infants in the stopped-drinking group showed more recovery over the first month than did those in the continued-drinking group in reflexive behavior and autonomic control. A reassessment at six months of 60 of the infants who had been tested at three days indicated that differences in orientation, motor performance, reflexive behavior and autonomic control were predictive of mental and motor performance on the Bayley Scales of Infant Development. This series of studies supports the contention that the negative effects on infant behavior of prenatal alcohol exposure are both immediate and persistent.

Alcohol Drinking↗
PubMed1987

Identifying high-risk pregnant drinkers: biological and behavioral correlates of continuous heavy drinking during pregnancy.

To determine whether women who continued to drink during pregnancy could be differentiated from women who discontinued alcohol use during their second trimester of pregnancy based on biological, social and behavioral data collected during a prenatal interview, 267 women receiving prenatal care at Grady Memorial Hospital, a large metropolitan hospital in Atlanta, were interviewed antepartum, assessing current drug and alcohol use as well as other demographic information. Postpartum interviews were conducted during the first 3 days following delivery to determine any changes in drug use or alcohol consumption that occurred after the first interview. Women who continued to drink throughout pregnancy and women who stopped drinking were similar on most demographic variables examined, including age, marital status, ethnic group, income, obstetrical complications risk score, amount of alcohol consumed per week and use of other drugs. Discriminant analysis was used to determine whether drinking-group membership could be predicted from self-reported drinking behaviors or biological and other demographic variables. The best predictors of drinking throughout pregnancy were the length of drinking history, reported tolerance to alcohol, a history of alcohol-related illness and drinking by siblings. In addition, women who continued to drink throughout pregnancy were more likely to report that they drank most often with other family members. Of the subjects who continued to drink, 81% were correctly classified based on this discriminant function. These findings suggest that women who continue to drink during pregnancy may be experiencing more chronic and severe alcohol-related problems than women who discontinue alcohol use and may thus be identified and targeted for intensive prevention effects.

Adult↗
PubMed1986

Coordinate and independent effects of heroin, cocaine, and alcohol abuse on T-cell E-rosette formation and antigenic marker expression.

Simultaneous and independent use of cocaine and alcohol by heroin addicts was shown to variably modulate the ability of their T cells to form E-rosettes with sheep erythrocytes (E). As reported previously, the percentages of E-rosette-forming T cells of both active and total types were depressed in association with heroin addiction. We show here that the kinetic curve of the rate of E-rosette formation is also depressed by heroin use and that the use of cocaine but not alcohol by heroin addicts reverses depression of E-rosette formation by heroin. The percentages of E-rosette-forming T cells from the bloods of heroin addicts who used both alcohol and cocaine, as well as the kinetic rate curves of E-rosette formation, were intermediate between the essentially normal levels found for heroin addicts who used cocaine and the severely depressed levels evident for users of heroin alone or heroin plus alcohol. Modulation of the levels of E-rosette formation by alcohol used in conjunction with cocaine and/or heroin was variably dose dependent. Polydrug effects evident by analyses of E-rosette formation were not seen when the percentages of lymphocytes reactive with LYT-3 (anti-E-receptor, 9.6 epitope) and OKT-3 (anti-total T cell) monoclonal antibodies were assessed cytofluorometrically, although the data suggested that subnormal percentages of LYT-3+ T cells were present when heroin addicts also used cocaine. These findings are relevant to basic understanding of T-cell physiology from a neuroimmunological perspective and also suggest ways that addictive drugs may modulate the immunocompetence of drug addicts.

Adult↗