European-American Children's and Adolescents' Evaluations of Interracial Exclusion.

No research, to date, has investigated the role of ethnic school composition (and intergroup contact) on European-American youth's use of stereotypes to explain interracial discomfort in the context of peer exclusion. In this study European-American 4th, 7th and 10th grade students (N = 414), attending low and high ethnically diverse public schools (with low and high self-reports of cross-race/ethnic friendships, respectively) evaluated three contexts of interracial exclusion (at lunch time, at a school dance, and at a sleepover). In addition to age and context effects, participants enrolled in high diversity schools were less likely to use stereotypes to explain racial discomfort, more likely to view racial exclusion as wrong, and more likely to estimate that racial exclusion occurs, than were participants enrolled in low diversity schools. These findings have implications for the role of social experience on racial attitudes and judgments about exclusion.

Outcome after extended follow-up in a prospective study of operable breast cancer: key factors and a prognostic index.

In 1990, 215 patients with operable breast cancer were entered into a prospective study of the prognostic significance of five biochemical markers and 15 other factors (pathological/chronological/patient). After a median follow-up of 6.6 years, there were 77 recurrences and 77 deaths (59 breast cancer-related). By univariate analysis, patient outcome related significantly to 13 factors. By multivariate analysis, the most important of nine independent factors were: number of nodes involved, steroid receptors (for oestrogen or progestogen), age, clinical or pathological tumour size and grade. Receptors and grade exerted their influence only in the first 3 years. Progestogen receptors (immunohistochemical) and oestrogen receptors (biochemical) were of similar prognostic significance. The two receptors were correlated (r=+0.50, P=0.001) and displaced each other from the analytical model but some evidence for the additivity of their prognostic values was seen when their levels were discordant.

Fairness or stereotypes? Young children's priorities when evaluating group exclusion and inclusion.

Seventy-two children (35 4 1/2-year-olds and 37 5 1/2-year-olds), nearly evenly divided by gender, from European American (71%), Asian American (17%), and African American (12%) middle-class backgrounds, were individually interviewed about straightforward exclusion and inclusion for two gender-stereotypic peer-group contexts: activities (doll and truck play) and role-play (teacher and firefighter). All children evaluated straightforward exclusion based on gender (e.g., girls excluding a boy from doll play) as wrong and used moral reasons. Preliminary inclusion decisions in the activity contexts (choosing a boy or a girl to join the group) were based on stereotypic expectations, particularly for younger children. Given the opportunity to weigh alternative considerations, however, all children gave priority to fairness over stereotypic expectations in both multifaceted inclusion peer-group contexts.

Children's social reasoning about inclusion and exclusion in gender and race peer group contexts.

This study investigated whether children's and adolescents' judgments about exclusion of peers from peer group activities on the basis of their gender and race would differ by both age level and the context in which the exclusion occurred. Individual interviews about exclusion in several different contexts were conducted with 130 middle-class, European American children and adolescents. Younger children were expected to reject exclusion, by using judgments based on moral reasoning, regardless of the potential cost to group functioning, whereas older children were expected to condone exclusion on the basis of group membership in cases in which the inclusion of these children might interrupt effective group functioning. On measures of judgments, justifications for those judgments, and ratings of the appropriateness of exclusion, the vast majority of children used moral reasoning and rejected exclusion in contexts in which only the presence of a stereotype justified it. As expected, however, older children (13 years) were more likely to allow exclusion than younger children (7 and 10 years) when group functioning was threatened, and they justified this exclusion by using appeals to effective group functioning.

Young children's evaluations of exclusion in gender-stereotypic peer contexts.

This study investigated how 50 preschool children (25 girls, 25 boys) evaluated the appropriateness of excluding boys and girls from two types of activities (doll play, truck play) and two types of future roles (playing a teacher, playing a firefighter) across different exclusion contexts. Children judged straight-forward exclusion from activities on the basis of gender as wrong, even if the child's gender was stereotypical of the activity. Furthermore, they justified these decisions on the basis of moral reasons, such as equality and unfairness. Children used a mixture of moral and social conventional reasoning (including stereotypes), however, to evaluate multifaceted situations that called for judgments about both inclusion and exclusion and that included information about the children's past experience with the activity.

The catalytic subunit of telomerase is expressed in developing brain neurons and serves a cell survival-promoting function.

Telomerase, a specialized reverse transcriptase (RT) linked to cell immortalization and cancer, has been thought not to be expressed in postmitotic cells. We now report that telomerase activity and its essential catalytic subunit, telomerase reverse transcriptase (TERT), are expressed in neurons in the brains of rodents during embryonic and early postnatal development, and are subsequently downregulated. Suppression of TERT expression in cultured embryonic hippocampal neurons increases their vulnerability to apoptosis and excitotoxicity. Overexpression of TERT in PC12 cells suppresses apoptosis induced by trophic factor withdrawal. TERT exerts its anti-apoptotic action at an early stage of the cell death process prior to mitochondrial dysfunction and caspase activation. TERT may serve a neuron survival-promoting function in the developing brain, and downregulation of TERT in the adult brain may contribute to increased neuronal vulnerability in various age-related neurodegenerative disorders.

Anti-apoptotic role of telomerase in pheochromocytoma cells.

Telomerase is a protein-RNA enzyme complex that adds a six-base DNA sequence (TTAGGG) to the ends of chromosomes and thereby prevents their shortening. Reduced telomerase activity is associated with cell differentiation and accelerated cellular senescence, whereas increased telomerase activity is associated with cell transformation and immortalization. Because many types of cancer have been associated with reduced apoptosis, whereas cell differentiation and senescence have been associated with increased apoptosis, we tested the hypothesis that telomerase activity is mechanistically involved in the regulation of apoptosis. Levels of telomerase activity in cultured pheochromocytoma cells decreased prior to cell death in cells undergoing apoptosis. Treatment of cells with the oligodeoxynucleotide TTAGGG or with 3,3'-diethyloxadicarbocyanine, agents that inhibit telomerase activity in a concentration-dependent manner, significantly enhanced mitochondrial dysfunction and apoptosis induced by staurosporine, Fe2+ (an oxidative insult), and amyloid beta-peptide (a cytotoxic peptide linked to neuronal apoptosis in Alzheimer's disease). Overexpression of Bcl-2 and the caspase inhibitor zVAD-fmk protected cells against apoptosis in the presence of telomerase inhibitors, suggesting a site of action of telomerase prior to caspase activation and mitochondrial dysfunction. Telomerase activity decreased in cells during the process of nerve growth factor-induced differentiation, and such differentiated cells exhibited increased sensitivity to apoptosis. Our data establish a role for telomerase in suppressing apoptotic signaling cascades and suggest a mechanism whereby telomerase may suppress cellular senescence and promote tumor formation.

Prospective evaluation of prognostic factors in operable breast cancer.

In 215 patients with operable breast cancer (T1-T3, N0-1, M0) and no other or previous cancer, presenting to a single breast unit, sufficient tumour was available for the prospective determination of four putative biochemical markers of prognosis: oestrogen receptor (ER) activity, cathepsin D (cath D), epidermal growth factor receptor (EGFR) activity and cyclic AMP-binding proteins (c-AMP-b). There were significant inter-relationships between ER and EGFR (r = -0.26), c-AMP-b and cath D (r = +0.32) and ER and c-AMP-b (r = +0.14). After follow-up (median 36.2 months), a total of 55 recurrences (18 locoregional only) and 35 deaths were recorded. By univariate analysis, up to 10 of 18 biochemical, clinical and histopathological variables of potential prognostic value were significantly related to disease-free interval or death, but by multivariate analysis only oestrogen receptor concentration and node status contributed significantly to risk of both distant recurrence/death; in addition, tumour size made a small contribution to the risk for a distant recurrence only. Only two parameters, tumour grade and ER concentration, were significantly related to risk of locoregional recurrence by univariate analysis, but by multivariate analysis, only tumour grade was important. It is concluded that tumour ER concentration, axillary nodal status and tumour grade remain as the most important prognostic factors in the early years after presentation of operable breast cancer, with a minor influence of tumour size. At this time, the prognostic significance of quantitative measurements of ER concentration, carefully controlled for the quality of both assay and tumour specimen, is probably greater than is generally appreciated. We have yet to identify other factors, which add significantly to the short-term prognostic value of these key features.

Children's evaluations of morality in the context of peer, teacher-child, and familial relations.

The purpose of this study was to investigate how children evaluate moral transgressions (rule violations that do not involve conflicts) and conflicts (stories involving peer, teacher-child, and familial relations) and how children weigh different issues and re-evaluate their decisions after hearing new information about the conflict. Results showed that children at all ages supported decisions by authorities (peer and adult) to ignore social order violations to prevent harm or a failure to share. Decisions to give preference to interpersonal relations were made for issues about harm but not about sharing resources. The findings demonstrate that children give priority to the prevention of harm and a failure to share for some, but not all types of moral conflicts, and that the salience of moral consequences influences their overall evaluation.

Granulocyte-macrophage precursor cell and colony-stimulating factor responses of mice infected with Salmonella typhimurium.

The response of granulocyte-macrophage progenitor cells (in vitro colony-forming cells) and of colony-stimulating (CS) factor in serum were studied in mice infected intraperitoneally with 10(3) viable Salmonella typhimurium. Increases in the number of colony-forming cells in marrow and spleen and increases in the serum level of CS factor occurred during the infection. There was no evidence to suggest that progressive infection was associated with failure of macrophage production. Medium rich in CS factor increased the bactericidal activity of macrophages in vitro and it was suggested that CS factor could be involved in macrophage activation.

Suppression of immune and hemopoietic cellular responses by methisazone.

The antiviral drug methisazone (N-methylisatin beta-thiosemicarbazone) was tested for its effect on immune responses to sheep erythrocytes and on hemopoietic colony-forming cell (granulocyte-macrophage progenitor cell) responses to complete Freund's adjuvant in mice. Suppressive activity was demonstrated in both systems, the immune system being more readily and more consistently susceptible. Evidence is presented which suggests that the insoluble particulate form of the drug has both stimulatory and suppressive effects on the colony-forming cell system, whereas the soluble form is only suppressive. Methisazone increased the mortality from ectromelia in adjuvant-treated animals.

Hemopoietic colony-forming cell responses in mice infected with ectromelia virus.

The responses of in vitro colony-forming cells (granulocyte-macrophage progenitor cells) were studied in the bone marrow, spleen, and blood of mice after intraperitoneal injection of 10(3) plaque-forming units of ectromelia virus. This study showed that a colony-forming cell response occurred during infection and was accompanied by an increase in the serum level of colony-stimulating factor and, at a later stage, colony-inhibiting factor. Changes in the proportions of colony-forming cells were not due to relative changes in other cell populations. The relationships between colony-forming cell responses and levels of infection were complex, higher levels of infection being associated with good colony-forming cell responses in bone marrow and apparently poor colony-forming cell responses in blood and spleen.