Search PubMed⌕ Search

Biomedical subjects

A Falek

Publications and source records attributed to A Falek.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

Morphine depression of T cell E-rosetting: definition of the process.

Two kinetic assays were developed to assess opiate effects on rates of T cell E-rosetting. The first adopted the thermal conditions of active E-rosetting assays (varying between 37 and 23 C) whereas the second incorporated cooler thermal conditions (varying between 0 and 29 C). In vitro treatment of lymphocytes with morphine depressed E-receptor levels and E-rosetting in both assays. With the 0-29 C procedure early stages of E-rosette formation were characterized by phase transition kinetics indicative of sequential gain and loss of E-rosettes. Assay thermal and erythrocyte (E) to T cell contact conditions, and the inclusion of morphine during E-rosetting, were independent variables that coordinately modulated the expression of phase transitions. Phase transitions were also noted during capping of total T cell E-rosettes at 37 C. The reason for phase transitions appears to be that T cells undergo sequential cycling of E-receptors, increasing because of the new expression of dormant E-receptors as the result of E-receptor microdisplacement and decreasing because E-rosettes are lost owing to patching and capping processes. According to this construction of the E-rosetting process, morphine inhibits E-rosetting and modulates expression of phase transitions by interfering with E-receptor microdisplacement processes. Presumably this interference by morphine is mediated through alteration of membrane fluidity and promotion of E-receptor coupling (and/or inhibition of uncoupling) to a transducer-effector component within the cell membrane. These findings and conclusions are specifically relevant to immunoregulatory processes and are also helpful for understanding the general nature of biological and physiological responses associated with receptor-ligand interactions.

Erythrocytes↗

Use of prenatal diagnosis among parents of infants with spina bifida in Atlanta, Georgia, 1976-1979.

A follow-up was made of the parents of a population-based cohort of 154 infants with spina bifida who were born in Atlanta during 1972-1979. We interviewed the parents of these infants and, for pregnancies after the spina bifida-affected birth, the ratio of use of prenatal diagnosis and the rate of recurrence of spina bifida were ascertained. Among 43 pregnancies which occurred in 1976 or later, and which occurred after a spina bifida-affected birth, prenatal diagnosis was used for 27 pregnancies (63%). For whites, among full siblings born after a spina bifida-affected birth, the recurrence rate for spina bifida was 2% (1/51). For blacks, among seven full siblings born after a spina bifida-affected birth, none was affected. Prenatal diagnosis appears to be well accepted among these parents of infants with spina bifida.

Adult↗

Increased rate of E-rosette formation by T lymphocytes of pregnant women who drink ethanol.

Ethanol use by pregnant women increased, in a dose-dependent manner, the rate of sheep erythrocyte rosette (E-rosette) formation with T lymphocytes. The time curve for E-rosette formation by T cells from nondrinking subjects was biphasic, with a rapid formation of half the E-rosettes within the first 16 min, followed by a much slower rate for E-rosette formation until the maximal T-cell percentage was reached overnight. For pregnant drinkers, greater than 85% of the E-rosettes formed during the initial rate period, with a concomitant smaller number forming during the overnight incubation. Despite the faster initial rate of E-rosette formation in the drinking subjects, the total percentage T cells was the same for both groups. Other demographic factors, like tobacco or marijuana use, or trimester, did not significantly contribute to the observed differences. An increase in the rate of E rosetting was also obtained by incubating lymphocytes from nondrinkers overnight in physiologically attainable concentrations of ethanol (less than or equal to 0.1%). These results demonstrate that drinking by pregnant women, even at relatively moderate levels (2 oz/week absolute ethanol), causes alterations in their cellular immune systems. With the ability of ethanol to cross the placental barrier and persist in utero, it is apparent that these levels of ethanol have the potential to affect the developing fetal immune system.

Alcohol Drinking↗

Neonatal ethanol withdrawal: characteristics in clinically normal, nondysmorphic neonates.

Although neonatal withdrawal syndrome is often noted in infants of narcotics addicts, ethanol withdrawal has been reported only among neonates with fetal alcohol syndrome. To examine the possibility that ethanol withdrawal occurs more widely and to identify its characteristics, the behavior of eight neonates born to women who drank a mean of 21 ounces of absolute alcohol per week during gestation was compared with that of two contrast groups: 15 infants whose mothers drank an equivalent amount but stopped in the second trimester, and 29 infants whose mothers never drank. None of the 52 infants had fetal alcohol syndrome, and all were in good health. Neurobehavioral evaluation 3 days postnatally compared the groups for the occurrence of characteristic signs of withdrawal from central nervous system depressants. Whereas there was no difference in the frequency of withdrawal symptoms among infants of mothers who never drank (mean 1.4) or of mothers who stopped drinking (mean 1.8), infants of mothers who continued to drink (mean 4.7) had significantly more tremors, hypertonia, restlessness, excessive mouthing movements, unconsolable crying, and reflex abnormalities. By interfering with state control and interactive behaviors, withdrawal could affect mother-infant bonding as well as the conditions that foster cognitive and social development.

Alcohol Drinking↗

Parallel increases in sister-chromatid exchanges at base level and with UV treatment in human opiate users.

The SCE base level frequency and SCE levels induced by far-UV (254 nm) treatment of cells in early G1 and early S phases of the cell cycle were significantly higher in leukocytes from heroin addicts as compared to controls. The increased SCE levels in addicts was greatest at base level and smallest after UV irradiation of cells in S phase. These results corroborate and extend our previous findings of increased chromosome damage and reduced DNA-repair synthesis in heroin users. Since opiates do not directly damage DNA, the elevated cytogenetic effects associated with opiate use probably arise from secondary promotional effects related to opiate-mediated alterations in leukocyte metabolism.

Crossing Over, Genetic↗

Factors related to onset age of Huntington disease.

One prominent feature of Huntington disease (HD) is the variable age at which the characteristic neurological or psychiatric symptoms appear. Ages of manifestation varying from 4 to 65 years are found in a sample of 95 HD pedigrees compiled since 1968 from the Southeastern United States. Significant parent-child correlations of age of onset indicate consistency of onset age within nuclear families. However, an average intrafamily range of 9 years and an average intrapedigree range of 12 years reveal substantial variability of onset age within these groups. Of the nine cases of juvenile-onset HD identified in this sample, seven were of paternal descent. The preponderance of juvenile patients inheriting the HD gene from a father confirms similar findings from other studies. In addition, a trend toward earlier onset in all offspring of paternal transmission suggests that the juvenile-onset phenomenon is only the tail of a shift in the curve of onset ages for this group. A trend toward earlier onset in successive generations was noted. This "anticipation" may reflect the finding that persons of early onset in prior generations are selectively nonreproductive as a result of manifestation of the disorder. By identifying familial factors influencing onset age of HD, it may be possible to more effectively evaluate environmental factors that influence the onset of the disorder.

Adolescent↗

Opiates and human chromosome alterations.

Cytogenetic studies on cultured lymphocytes showed an increase in the frequency of chromosome breaks in heroin addicts (2.6%) compared to controls (0.4%). Within the first year, patients on methadone maintenance had a decline in the frequency of chromosome damage. Investigation of former addicts who had not been exposed to heroin for over one year revealed a remarkably low frequency of cells with damage for both methadone users (0.8%) and for those not using methadone (0.6%). These results indicate that long-term treatment programs reverse the cytogenetic alterations found in heroin users.

Adult↗

Alteration of T and null lymphocyte frequencies in the peripheral blood of human opiate addicts: in vivo evidence for opiate receptor sites on T lymphocytes.

Street opiate addiction produces a significant depression in the absolute number of total T lymphocytes in peripheral blood as measured by the ability of the lymphocytes to rosette sheep red blood cells (SRBC). Associated with the decrease in T cells, there is an increase in the absolute number of null lymphocytes but no significant changes in B lymphocytes or total white blood cell count. The T cell values for 2 different populations of addicts (n = 12 and 32) are 31.8% and 23.1%, whereas the null cell values are 51.1% and 57.6%, respectively. The values for comparable control populations (n = 18 and 10) are: T% = 70.7% and 67.4%, and null % = 9.2% and 14.5%. Self-reported use of marihuana does not significantly alter the distribution of cell populations. A 1- to 3-hr incubation of addicted-derived lymphocytes with 10(-6) to 10(-7) M Naloxone reverses both T cell depression and null cell increase by allowing the null cells to express SRBC receptors. Cyclic AMP and dibutyryl cyclic AMP can also convert the null cells to T cells. The conversion of null to T lymphocytes has additionally been measured by monitoring the increase in PHA-stimulated growth in 72-hr cultures as determined by tritiated thymidine incorporation into DNA. These results support the hypothesis that opiates can alter T lymphocyte number and function in vivo, and that this alteration may produce a significant degeneration in the immune competence of street opiate addicts.

B-Lymphocytes↗