Dehydroisoandrosterone prevention of autoimmune disease in NZB/W F1 mice: lack of an effect on associated immunological abnormalities.

The effect of dietary dehydroisoandrosterone (DHA) on several immunological abnormalities associated with the development of systemic lupus erythematosus in New Zealand Black/New Zealand White F1 (NZB/W) female mice was examined. Despite the extraordinary benefits in prolonged survival and decreased synthesis of antibodies to double-stranded DNA obtained by adding DHA (0.4% w/v) to the diet fed to these mice (Lucas et al. (1985) J. Clin. Invest. 75, 2091-2093), remarkably small changes in the chemistry and function of the immune system were detected. DHA prevented the increases in spleen mass and in peritoneal cell number which occur with age in NZB/W female mice, but did not prevent the development of hypergammaglobulinemia. DHA did not affect peritoneal macrophage functions as measured by the phagocytosis of opsonized and non-opsonized sheep erythrocytes, or the zymosan-stimulated release of PGE2, 6-ketoPGF1 alpha, TXB2 and LTC4. In spleen, DHA delayed the loss of T-cell mitogenic responses until 5.5 months of age, but did not alter the spleen lymphocyte population.

Liver composition and lipid metabolism in NZB/W F1 female mice fed dehydroisoandrosterone.

The beneficial effects obtained with dehydroisoandrosterone (DHA) feeding in the treatment of murine systemic lupus erythematosus are similar to those obtained with caloric restriction or with dietary manipulation of essential fatty acid availability. In this study, the fatty acid composition of selected tissues was examined in NZB/W F1 mice fed a diet containing 0.4% DHA. The effect of the DHA diet on liver composition and the activity of key hepatic enzymes involved in fatty acid synthesis and glucose metabolism was also investigated. The content of the essential fatty acid, arachidonate, was decreased in plasma cholesteryl esters and liver and kidney phospholipids in mice fed the DHA diet, yet no significant decrease in arachidonate content was observed in plasma phospholipid. The most striking change in both plasma and liver phospholipid was an increase in palmitic acid and a decrease in stearic acid, which could result from a decreased ability for fatty acid elongation. The liver mass was dramatically increased in the mice fed DHA, primarily from parenchymal cell hypertrophy, and contained little lipid. Significant changes in the activities of malic enzyme, glucose-6-phosphate dehydrogenase and pyruvate kinase, similar to those changes which occur with fasting, were observed during the initial adaptation to the DHA diet. The pyruvate kinase activity remained low, suggesting a decrease in liver glycolysis. These results are consistent with the concept that diets containing DHA result in an altered metabolism with a decreased dependence on carbohydrate metabolism and an increased metabolism of lipids.

In vivo effects of lipopolysaccharide on hepatic free-NAD(P)(+)-linked redox states and cytosolic phosphorylation potential in 48-hour-fasted rats.

This study was performed to determine the magnitude and time of onset of in vivo changes in hepatic bioenergetics in response to a sublethal dose of lipopolysaccharide (LPS), a bacterial endotoxin. Male rats (48-hour-fasted) were administered an intraperitoneal injection of LPS (5 mg/kg body weight) or vehicle alone, and the livers were freeze-clamped 5, 30, or 180 minutes or 24 hours later. Liver tissue was extracted with perchloric acid, and the metabolites necessary to calculate NAD(+)- and NADP(+)-linked redox states and the cytosolic phosphorylation potential were measured. There was no significant difference in hepatic cytosolic phosphorylation potential between LPS and control groups at any of the times investigated. This indicated that the ability of the liver to synthesize adenosine triphosphate (ATP) was not compromised under the conditions of the study. No changes in hepatic redox states were observed 5 or 30 minutes after LPS treatment. Three hours after LPS treatment, hepatic cytosolic and mitochondrial free-[NAD+]/[NADH] redox states and the cytosolic free-[NADP+]/[NADPH] redox state were more oxidized. By 24 hours, only NAD(+)-linked redox states were more oxidized than the time-matched controls. Hepatic urea content was elevated at both 3 and 24 hours, compatible with an increased rate of urea synthesis as a consequence of increased amino acid metabolism, whereas hepatic beta-hydroxybutyrate and total ketone bodies were decreased 24 hours after LPS treatment, indicating decreased hepatic ketogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Methionine enkephalin metabolism by murine macrophage ectopeptidase(s).

Ectopeptidases which hydrolyze opioid and other neuropeptides have been identified in brain, kidney and intestine. In this study, identification of the enzymes metabolizing the opioid peptide methionine enkephalin (YGGFM) in murine macrophages was undertaken. Incubation of methionine enkephalin with intact murine peritoneal macrophages results in five products identified as Y, F, FM, GFM and GGFM by amino acid analysis and peptide microsequencing after fractionation by HPLC. The spectrum of metabolites results from at least two distinct aminopeptidase activities. The enzyme hydrolyzing YGGFM to GGFM is identified as the membrane-anchored aminopeptidase N (ApN; EC 3.4.11.2) based on its substrate specificity and inhibitor profile. A distinct bestatin and amastatin sensitive aminopeptidase catalyzes hydrolysis of GGFM to GFM. The macrophage ApN protein has a larger mass and is antigenically distinct from murine kidney ApN, which is suggested to result from glycosylation differences rather than expression of a distinct protein. The ApN catalytic activity and mRNA levels are increased in thioglycollate-elicited as compared to resident peritoneal macrophages. RT-PCR analysis identified a 0.7 kb fragment of the ApN coding sequence which was identical in mouse kidney and thioglycollate-elicited peritoneal macrophages and which has 89% identity with the corresponding rat kidney ApN cDNA sequence.

Adopted adolescents' overrepresentation in mental health counseling: adoptees' problems or parents' lower threshold for referral?

UNLABELLED: A larger proportion of adopted adolescents receive mental health counseling than do their nonadopted peers. Adoptees might have more problems that require counseling, or their adoptive parents might have a lower threshold for referral (or both). OBJECTIVE: To test the hypothesis that both the extent of adolescents' problems and their adoption status would predict whether adolescents received psychological counseling, after controlling for family demographic characteristics. METHOD: Two large data sets collected from 1994 through 1996 by the National Longitudinal Study of Adolescent Health (Add Health) were used. In parallel analyses of the 2 data sets, hierarchical logistic regression models were implemented to assess the incremental effects of problem behaviors, family characteristics, and adoption status on adolescents receiving counseling. RESULTS: Selected adolescents' problems and family demographic characteristics were significant predictors for having received counseling, but, after controlling for these variables, adoptees were still about twice as likely as nonadoptees to have received counseling. CONCLUSIONS: Prevalence of problems, adoptive family characteristics, and adoption status must all be taken into account to understand why adoptees are more likely to receive counseling. Clinicians should be sensitive to issues that are especially salient in adoptive families.

Characteristics of effective day treatment programming for persons with borderline personality disorder.

Day treatment, or partial hospitalization, may have unique advantages for the treatment of patients with borderline personality disorder. Such treatment may offer patients the optimal level of intensiveness and containment, resulting in less regressive dependency and acting-out behavior. To be successful in treatment of patients with borderline personality disorder, a day treatment program should facilitate the patient's need to experience and express affect safely, optimize the program's ability to provide less restrictiveness than inpatient treatment but more sustained and intensive support than outpatient treatment, and use verbal and nonverbal approaches to help patients maintain primary responsibility for their well-being. A length of stay of three weeks allows patients to regain baseline functioning and resume long-term outpatient care. Treatment goals should be clear and resolvable in three weeks.

Changes in reports and incidence of child abuse following natural disasters.

OBJECTIVE: The aim of this research was to investigate if there is a higher incidence of child abuse following major natural disasters. METHODOLOGY: Child abuse reports and substantiations were analyzed, by county, for 1 year before and after Hurricane Hugo, the Loma Prieta Earthquake. and Hurricane Andrew. Counties were included if damage was widespread, the county was part of a presidential disaster declaration, and if there was a stable data collection system in place. RESULTS: Based on analyses of numbers, rates, and proportions, child abuse reports were disproportionately higher in the quarter and half year following two of the three disaster events (Hurricane Hugo and Loma Prieta Earthquake). CONCLUSIONS: Most, but not all, of the evidence presented indicates that child abuse escalates after major disasters. Conceptual and methodological issues need to be resolved to more conclusively answer the question about whether or not child abuse increases in the wake of natural disasters. Replications of this research are needed based on more recent disaster events.

The effects of forced sexual intercourse on white female adolescents.

In the 1987 National Survey of Children the question was asked: "Was there ever a time when you were forced to have sex against your will, or were you raped?" Among White females, aged 18-22, those who answered yes (n = 41) and no (n = 400) were compared on a number of social-psychological and sexual variables that might be thought of as outcomes affected by having had coercive sexual experience(s). Those who reported being forced to have sexual intercourse, compared to those who did not, had more permissive attitudes about 16-17-year-olds having intercourse and a younger age of first voluntary sexual intercourse themselves. They also had lower internal locus of control and higher depression scores, and they needed and received more psychological help than those not reporting forced sexual intercourse. Dividing the forced sexual intercourse group (FSI) into those reporting FSI before versus after their first date, and those whose FSI was before versus after age 12, yielded essentially the same findings. Even in the presence of multivariate control variables. FSI experience remained a significant predictor of age at first voluntary sexual intercourse, locus of control, depression, and perceived need for psychological help. These analyses of national survey data support the clinical perspective that forced sexual intercourse causes or exacerbates various sexual and psychological problems.

Dating age and stage as correlates of adolescent sexual attitudes and behavior.

Dating experiences, especially the type or stage of dating, have consistently been found to be related to premarital sexual behavior. Findings regarding the age at 1st date and sexual behavior have been less consistent. This paper examined the age at which dating began and the type of dating relationship as correlates of premarital sexual attitudes and behavior among mid-teen adolescents. The analyses were based on a sample of high school students (n=836), most of whom were between the ages of 15 and 18 when the surveys were conducted. Early dating, especially early steady dating, was related to permissive attitudes and to premarital sexual experience among both males and females. The relationship between early dating and intercourse experience was particulary strong among Mormons, a religious group which has institutionalized age 16 as the legitimate age to begin dating.

Correlates of age at first sexual intercourse in a national sample of young women.

A subsample of 814 sexually experienced adolescent females from the 1979 U.S. National Survey of Young Women was analyzed to assess the correlates of age at 1st sexual intercourse. Multiple regression procedures were used to examine sets of variables sequentially. In the hierarchical regression model, the control variables (respondent's age, race, religion, and age at menarche), along with 3 independent variables (household income, ideal age at 1st marriage, and ideal age for 1st birth), predicted age at 1st intercourse. The control variables accounted for a major portion of the variance in the model. Of the controls, chronological age and age at menarche were highly significant across all models tested.

Academic goals, achievement, and age at first sexual intercourse: longitudinal, bidirectional influences.

This study examined bidirectional relationships between age at first sexual intercourse and academic goals and achievement. It was hypothesized that lower educational goals and achievement would be associated with initiating sexual intercourse at a younger age, and that initiating sexual activity early would be associated with a decrease in subsequent academic achievement and goals. In longitudinal data spanning 11 years, evidence was found for bidirectional effects. One interpretation of these results is that adolescents with high educational goals and achievement delay having intercourse because of the perceived risks (e.g., pregnancy and sexually transmitted diseases may jeopardize their plans for the future). Conversely, adolescents who engage in sexual intercourse at young ages might undergo a change in attitudes, including reduced interest in academic achievement and goals. The specific educational variables most strongly related to adolescent sexual intercourse in this study differed substantially by race and gender.

Adolescent fertility-related behavior in the 1990s: risking the future continued.

PIP: Sexual intercourse and contraceptive use are fertility-related behaviors. Such behavior affects the risks of adolescent pregnancy, abortion, birth, adoption, and parenthood. The issue of adolescent sexuality gained prominence during the 1980s. This paper introduces and briefly reviews a group of five empirical studies which focus upon the fertility-related behavior of adolescents in the 1990s. Synopses of each study are provided. The authors find that these articles shed considerable light upon the many issues involved in adolescent sexual behavior. They are based upon some of the richest and most recent data sets available. As the 1990s begin, there is no indication that adolescents will decrease their level of sexual activity, and it is too soon to tell whether the apparent recent increase in condom use will result in lower pregnancy rates.^ieng

Adolescent parenthood, economic issues, and social policies.

PIP: Economic disadvantage and limited opportunities have been viewed as fundamental causes of adolescent pregnancy and childbearing. Adolescents who become pregnant and bear children, however, often suffer adverse social and economic consequences. Much of the economic burden of raising these children falls upon extended family members and the public sector. Socioeconomic disadvantage is thus a cause and a consequence of adolescent pregnancy and childbearing, with women who become mothers as teenagers at greater risk of social and economic disadvantage throughout their lives than those who delay childbearing until their twenties. They are less likely to complete their education, to be employed, to earn high wages, and to be happily married. These women are also more likely to have larger families and to receive welfare. The author reviews and summarizes recent research and revisionist debates on these issues, and considers the implications for social policy. Emphasis is given to prevention approaches which build upon postponing adolescent sexual intercourse and helping sexually active teens avoid pregnancy.^ieng

Hormonal regulation of L-type pyruvate kinase in rat liver cells in culture.

An immortalized rat liver cell line (RLC) expresses two isozymes of pyruvate kinase, the adult liver or L-type isozyme and an M-type isozyme presumed to be the M2-type. In RLC cells incubated in serum-free medium, the addition of 0.1 microM insulin maintained the initial level of L-type pyruvate kinase when it was high and induced the L-type isozyme when it was low. The addition of 1.0 mM dibutyryl cAMP and 0.5 mM theophylline decreased the L-type isozyme, even in the presence of insulin. The amount of M2-type isozyme was relatively constant under the conditions used. Regulation of the amount of L-type pyruvate kinase by both insulin and cAMP occurred primarily through changes in the rate of L-pyruvate kinase protein synthesis and translatable mRNA levels. These results are consistent with the in vivo observations that both insulin and glucagon regulate the rate of L-pyruvate kinase gene transcription and that cAMP is the dominant regulator of L-pyruvate kinase gene expression.