Effectiveness of attachment based STEEP™ intervention in a German high-risk sample.

STEEP(TM) was one of the first attachment-based early intervention programs. The program applied findings from the Minnesota Longitudinal Study on Risk and Adaptation to the development of a supportive program for young high-risk mothers and their infants. STEEP's effectiveness was evaluated first in a randomized controlled study launched in 1987. The study showed effects of the one-year intervention on important individual and parenting variables, but not on quality of mother-infant attachment. In the current German study with young mothers at risk for abuse and neglect, a two-year adaptation of STEEP was evaluated within a quasi-experimental design. STEEP mother-infant pairs (N = 78) were compared with pairs who received standard services of the German Child Welfare System (GCWS, N = 29). Compared with GCWS pairs, significantly more mother-infant pairs in the intervention group showed secure attachment patterns in Ainsworth´s Strange Situation when the infants were 12 months of age. At the end of the intervention (infant age = 24 month), attachment security scores derived from Waters' Attachment Q-Sort were in the predicted direction and showed a medium effect size, but did not reach criteria of statistical significance. At both time points, the STEEP group showed significantly fewer signs of attachment disorganization than the comparison group.

Foster children's attachment security and behavior problems in the first six months of placement: associations with foster parents' stress and sensitivity.

Both traumatic experiences in their birth families and multiple placement histories lead to increased mental health problems in foster children. The formation of secure attachments to new caregivers could be a protective factor for foster children. The current study focused on the associations between foster parents' sensitivity, parenting stress and foster children's attachment behavior as well as behavior problems. The sample consists of 48 children (aged from 1 to 6 years) and their foster caregivers. Attachment behavior and sensitivity were observed during home visits. Furthermore, caregiver reports were used to assess parenting stress and children's behavior problems. Compared to normative data, foster children showed lower levels of attachment security and more behavior problems. Foster children's attachment security and behavior problems were predicted significantly or marginally by foster parents' stress and supportive presence.

The association of prenatal attachment and perinatal factors with pre- and postpartum depression in first-time mothers.

PURPOSE: This prospective study investigated associations between prenatal attachment of adult first-time mothers to the unborn child, perinatal factors and levels of depression before and up to 18 months after delivery. METHOD: Primiparas (N = 161) without specific risk factors answered the following questionnaires during the last term of pregnancy (t1): Edinburgh Postnatal Depression Scale (EPDS), Maternal Antenatal Attachment Scale (MAAS), questionnaire on the schema of the unborn child, and a questionnaire about the pregnancy. Perinatal data were taken from the patients' files. The EPDS was answered 3 weeks (t2, N = 157), 6 months (t3, N = 159), and 18 months (t4, N = 132) postpartum. RESULTS: During pregnancy, 16.9 % of the women indicated mild depressive symptoms, and 7.5 %, medium to severe symptoms of depression. Mild symptoms of depression were found in 25.5 % at t2, 10.1 % at t3, and 12.2 % at t4; medium to severe symptoms were reported by 7.6, 1.9 and 5.6 %, respectively. Women with low control during delivery (emergency Caesarean) showed a tendency for higher levels (p = 0.067) of depression at t3 than women with elective Caesarean did. The quality of prenatal attachment to the unborn child correlated negatively with depressive symptoms at t1-t4. CONCLUSIONS: The closer the prenatal attachment of a mother to her unborn child, the less symptoms of depression she reports during the last term of pregnancy and postpartum. Therefore, promoting good mother-child attachment during pregnancy might influence the level of postpartum depression.

Child Abuse and Neglect: Screening for Risks During the Perinatal Period.

Purpose: Currently, there is a claim for earlier interventions for families in order to prevent child maltreatment. Here, a screening instrument to assess risk indicators for child abuse and neglect already in the context of maternity clinics is introduced. The present study is the first report on the psychometric properties of this instrument, the "short questionnaire for risk indices around birth" (RIAB). Material and Methods: Data were collected in the context of three different studies conducted at Ulm University Hospital. To examine interrater reliability eight case vignettes were rated by n = 90 study participants (50 students and 40 experts working at a maternity clinic). Criterion validity was examined in two studies applying the German version of the child abuse potential inventory CAPI (n = 96 families at risk and n = 160 additional families). Results: Both laymen and experts were able to understand and use the screening instrument correctly, leading to a high agreement with the sample solutions given. A high concordance was found between parents' and experts' ratings: In case of no reported risk factors applying the screening instrument RIAB, parents themselves reported significantly less stressors and burdens, compared to those parents with an indication for a thorough examination as pointed out in the RIAB. Conclusion: In the context of maternity clinics the RIAB is a useful, broadly applicable instrument, screening for existing risk factors at the earliest and thus allowing for the initiation of specific interventions when needed.

The specificity of infant emotional expression for emotion perception.

Attachment theory emphasizes the role of negative emotional expression in infancy for establishing proximity to and care of the caregiver. According to Lang's biphasic model of emotions protective reflexes (e.g. startle response) are primed if a defensive motivational set is activated. The aim of the study was to examine whether the perception of an infant emotional expression can prime such defensive behavior. The sample consisted of 48 university students. Startle reflex, corrugator and zygomatic EMG activity and subjective ratings of valence and arousal were assessed as a response to presentation of pictures of different emotional valence. Affective startle modulation was obtained when probes were presented during pictures of the International Affective Pictures System replicating previous findings. By contrast, negative infant emotion pictures did not prompt an augmentation of the startle response, although both the subjective ratings and the mimic EMG activity indicated a clear differentiation between negative and positive infant pictures. This pattern of findings was found only in a between-subject design, but not when the two picture sets were presented in the same session, indicating an interference of contrasting content of pictures.

Attachment representation and emotion regulation in adolescents: a psychobiological perspective on internal working models.

Attachment theory claims that inner working models of attachment substantially control behavioral and emotional regulation. There are different levels of organization of the attachment system following a developmental sequence from basic attachment behaviors at newborn age to a procedural organization in terms of behavioral strategies at the end of the first year to a representational organization later on. Also, the organismic systems underlying emotions and emotional regulation may occur and may be described on different organizational levels. Inner working models are seen as regulatory mechanisms for the interplay between the different organismic systems underlying emotions and emotional regulation. This paper will concentrate on biobehavioral organization. Combining assumptions of attachment theory with assumptions about biobehavioral function may provide the possibility of validating theoretically derived interpretations of the attachment system. Including the physiological processes in addition to the psychological processes enables us to test assumptions about the function of the inner working model with respect to processes that are not accessible by verbal communication and that are not expressed through overt behavior. The paper will provide theoretical and empirical evidence for the contribution of the inner working model of attachment to emotional perception, emotional expression and the coherence of inter-modal organization. The empirical findings suggest that from a developmental perspective the inclusion of different levels of regulation may provide possibilities of studying continuity and stability of individual differences of the attachment system during the life-course both within and across levels.

Epstein-Barr virus in nasal lymphomas contains multiple ongoing mutations in the EBNA-1 gene.

We have described 5 major subtypes of Epstein-Barr virus (EBV) based on variations in EBNA-1 sequences. These include P-ala (identical to the prototype B95.8 virus), P-thr, V-pro, V-leu, and V-val. Normal individuals often carry multiple EBV subtypes, the most common being P-ala, whereas EBV-associated tumors examined to date always contain a single subtype, which only on rare occasion is P-ala. The primary hypotheses that these observations generate are as follows: (1) Each of these EBV subtypes are naturally occurring, and in normal individuals the multiplicity of subtypes results from multiple infections. (2) EBV subtypes in normal individuals are generated in vivo from a single infecting virus subtype by mutations in EBNA-1. The second hypothesis essentially excludes the possibilities that the nonrandom association of certain subtypes with lymphomas is secondary to the geographic distribution of EBV subtypes and, if proven correct, could provide strong support for a direct role of EBV in tumorigenesis. In this report, we provide evidence for the latter hypothesis. We show that the P-ala EBV subtype present in most nasal lymphomas undergoes and accumulates multiple mutations consistent with the generation of variant species of EBNA-1 in vivo. This phenomenon is similar to the generation of quasispecies in RNA viruses and is the first description of in vivo generation of subtypes in DNA viruses. In RNA-based viruses, including human immunodeficiency virus and hepatitis C virus, the emergence of quasispecies is linked to replication infidelity and significantly influences disease processes through its effect on viral tropism, the emergence of viruses resistant to the host defenses or to therapy, and pathogenicity. The present data thus raise important questions relating to the mechanisms whereby these mutations are generated in EBV and their relevance to the pathogenicity of EBV-associated lymphomas.

Enamel structure and composition in the tricho-dento-osseous syndrome.

Tricho-dento-osseous syndrome (TDO) is an autosomal dominant disorder characterized by curly hair, hypoplastic enamel, taurodontism, and dense bone. The purpose of this investigation was to characterize the enamel defects in a TDO population in North Carolina. Twelve TDO teeth and 12 normal teeth were examined. The enamel thickness was decreased in all TDO teeth ranging from having no enamel to about 60% the thickness of normal teeth. Half of the TDO teeth had primarily prismless enamel while the remainder had at least occasional areas of prismatic enamel. TDO enamel crystallites appeared similar to normal crystallites with TEM. The mineral per volume of TDO enamel (n = 9) (68.5%) was significantly less, on average, compared with normal enamel (n = 8) (84.5). The genetic mutation responsible for the TDO phenotype results in alteration of a developmental pathway(s) common to hair, teeth and bone. This further illustrates that these embryologically diverse tissues share common developmental controls at the molecular level.

Psychological and physiological responses during an exam and their relation to personality characteristics.

The aim of the study was to compare emotional and physiological responses to real and control examinations and to assess their relation to personality characteristics. Emotional responses were assessed by state anxiety and perceived stress. The assessment of physiological responses included the activity of the cardiac system (heart periods, vagal tone), the adrenocortical system (cortisol) and the immune system (immune globulin A, sIgA). Emotional and physiological responses of 23 students (12 males, 11 females) were assessed during an oral exam at the end of a basic course in psychology which was a prerequisite for the students' final exams. For the control condition physiological responses were assessed one week before the examination during a memory test. The findings of the study demonstrate different emotional and physiological response patterns to examinations as compared to the control condition. Heightened anxiety was observed only before the exam. Whereas within-situation physiological responses (higher heart periods, cortisol, and sIgA; lower vagal tone) were observed both under the exam and control condition, responses to exam condition indicated pre-exam anticipatory activation and post-exam restricted recovery responses. With regard to personality characteristics subjects with high ego-resiliency showed more flexible adaptation than subjects with low ego-resiliency both on the emotional level (anxiety down-regulation after exam) and on the physiological level (situation-specific responses, quick recovery). Subjects with high ego-control exhibited a lower physiological reactivity under both conditions, i.e. they seemed to maintain longer their control also on a physiological level independent of the type of situation.

Sequence variations in EBNA-1 may dictate restriction of tissue distribution of Epstein-Barr virus in normal and tumour cells.

In seropositive individuals Epstein-Barr virus (EBV) establishes a virus reservoir in peripheral blood lymphocytes (PBLs). Transmission from one individual to another occurs via saliva due to a lytic (virion productive) phase of infection in the oropharynx. EBNA-1 is responsible for maintaining viral episomes in the host cell and could, therefore, also affect the persistence of the virus in different cell lineages. Based on sequence analysis of EBNA-1 we now demonstrate that (i) in addition to the prototype EBNA-1 (identical to the B95.8 virus EBNA-1), EBV in normal individuals encompasses multiple EBNA-1 subtypes, both in PBLs and in oral secretions; (ii) although EBV with prototype EBNA-1 is the predominant virus in normal individuals, it is very rarely associated with either nasopharyngeal carcinoma (NPC) or Burkitt's lymphoma (BL); (iii) EBV with an EBNA-1 subtype (V-val) frequently associated with NPC is also selectively detected in oral secretions and not in PBLs; (iv) EBV with the EBNA-1 subtype V-pro is restricted to PBLs, while a mutated version of this subtype is present in BL, but not in NPC. These findings suggest that the variations in EBNA-1 may be relevant to the ability of EBV to persist in different cell types, and hence relevant to its oncogenic potential.

Variation in the sequence of Epstein Barr virus nuclear antigen 1 in normal peripheral blood lymphocytes and in Burkitt's lymphomas.

We have examined sequence variations in the EBNA-1 protein of EBV in normal peripheral blood lymphocytes (PBL) and Burkitt's lymphomas (BL). We find two EBNA-1 strains P (prototype) and V (variant) which differ by 15 amino acids. Each strain has two subtypes defined by the amino acid at position 487 (P-ala, P-thr, V-pro and V-leu). In PBLs from 32 normal individuals, up to three of these subtypes were found in each sample, but the V strain did not occur in the absence of P strain viruses, nor was the V-leu subtype ever observed in normal PBL. In BLs only a single subtype was observed in each tumor. The P-thr and V-leu subtypes were more frequently seen than the P-ala and V-pro subtypes, which occurred in only two and one of the 36 tumor samples respectively. The P-thr was the most commonly observed subtype in peripheral blood of both American and African lymphocytes as well as in African tumors. However, in 11 of 12 American tumors, the EBNA-1 subtype was V-leu. These data indicate that some EBNA-1 subtypes are more likely to lead to oncogenesis, and one subtype, V-leu, appears only to occur in tumors.

Use of Epstein-Barr virus nuclear antigen-1 in targeted therapy of EBV-associated neoplasia.

To target expression of toxic genes to Epstein-Barr virus (EBV)-associated tumor cells, we have developed an EBV-driven enzyme prodrug system (EDEPS) that takes advantage of the trans-activating properties of EBNA1, a latent protein expressed in all EBV-containing cells, to direct expression of cytosine deaminase (CD) at high levels in those cells only. Plasmids were constructed in which the CD gene or a luciferase reporter gene were cloned downstream of the herpes simplex virus thymidine kinase (tk) promoter and the family of repeats (FR) sequence from the oriP region of EBV. Analysis of luciferase activity after transient transfection into a panel of EBV-negative or -positive human cell lines showed that the presence of the FR element enhanced transcription from the tk promoter in all EBV-positive cell lines, whereas transcription from tk was repressed in all EBV-negative cell lines, including B, T, and fibroblast cell lines. In clonogenicity assays following transfection with the CD vector, the presence of 5-fluorocytosine (5-FC) in the culture medium completely abolished cell growth in EBV-positive cell lines, but did not affect the growth of EBV-negative cell lines. This vector system should have wide applicability in that it allows targeted expression of any gene of interest to tumors that carry EBV, irrespective of the role EBV plays in their pathogenesis.

A mutant p21 cyclin-dependent kinase inhibitor isolated from a Burkitt's lymphoma.

The growth arrest mediated by p53 is caused at least in part by the p53 mediated expression of p21 (p21waf1/Cip1). Since only one-third of primary Burkitt's lymphomas (BL) demonstrate mutations in the p53 gene, we examined the structural integrity of the p21 coding region by single-strand conformational polymorphism and DNA sequence analysis to determine the extent to which this gene is mutated in BL. Of 34 BLs analyzed, a frequent change (38%) at codon 31 that replaced Ser with Arg was found in 13 samples, 10 of which were from Africa. This change at codon 31 is also detected in peripheral blood DNA from normal subjects and may thus represent a polymorphism. One BL cell line, DH978, carried a change at codon 63: Phe to Leu. This mutation was heterozygous, and both the wild-type and the mutated p21 mRNA were expressed in the tumor cell line. By transfection experiments, the mutant p21 was less efficient in suppressing clonogenicity than wild-type p21. To our knowledge, this is the only mutation described in p21. The availability of this mutant p21 should further help in functional studies of p21.

Mutations in the coding region of c-myc occur independently of mutations in the regulatory regions and are predominantly associated with myc/Ig translocation.

Constitutive expression of c-myc resulting from a chromosomal translocation, which juxtaposes c-myc to an immunoglobulin gene, is a pivotal lesion in Burkitt's lymphomas. This deregulated expression of c-myc is associated with mutations in the regulatory regions, i.e. the first exon and the first intron of c-myc in tumors where the chromosomal breakpoint is not itself within the regulatory region. Until recently it was widely believed that the c-myc protein in these tumors is wild type. We have demonstrated that in a fraction of Burkitt's lymphomas from Africa and from the continental USA, and in mouse plasmacytomas, the c-myc gene carries mutations in the coding region. We now show that, occasionally, such mutations are also present in multiple myelomas--tumors which do not carry translocations or amplifications of c-myc. We also show that the frequency of the c-myc coding region mutations in BL is independent of the frequency of mutations in the regulatory region. These results suggest that the mechanisms that induce missense mutations involving the coding region of c-myc may be different from those that lead to mutations in the regulatory regions.

Maternal sensitivity as an external organizer for biobehavioral regulation in infancy.

Recent findings from both animal and human research have clearly demonstrated connections between behavioral coping mechanisms and adrenocortical function. The aim of this study was to address the role of maternal sensitivity as an external organizer of psychobiological function in infants during the first year of life. Forty-one infants and their mothers were observed during play at 3, 6, and 9 months of age. Age-specific patterns of relation between maternal sensitivity and infant behavioral organization were found indicating contextual dependence of infant behavior at 3 months and experience-related behavioral function at 9 months. An affect of maternal sensitivity on adrenocortical function during the free play was demonstrated at 3 and 6 months, because an increase in cortisol was most frequently observed in infants of highly insensitive mothers. The findings indicate the importance of maternal behavior for infant biobehavioral organization.

Mutations in the coding region of c-myc occur frequently in acquired immunodeficiency syndrome-associated lymphomas.

We have analyzed 30 cases of high- and intermediate-grade acquired immunodeficiency syndrome-associated non-Hodgkin's lymphoma (AIDS-NHL) for mutations in the c-myc coding region. In addition, in these same tumors, we have sought the presence of mutations in a regulatory region within the first c-myc intron defined by the binding to a factor that inhibits c-myc transcription (MYC intron factor, or mif). Mutations in the c-myc coding region were present in 10 of 16 small noncleaved cell lymphoma (SNCL), but in only 3 of 14 other histologic subtypes tested (0/3 large non-cleaved cell, 2/8 immunoblastic, and 1/3 anaplastic large cell lymphomas). Nineteen of the AIDS-NHLs analyzed contained a c-myc rearrangement and in 10 of these the c-myc gene was mutated in its coding region. In contrast, we could detect a mutation in the coding region in only 2 of 8 AIDS-NHL without a c-myc rearrangement. Mutations in the mif region were detected in 5 of 16 SNCL. Among AIDS-NHL carrying mutations in the c-myc coding region, only 4 carried mutations in the regulatory region. These results suggest that the mutations in the coding region of the c-myc protein may either be a consequence of the translocations involving c-myc, or may be necessary only in tumors where c-myc is deregulated as a result of a c-myc/lg translocation.

Biobehavioral organization in securely and insecurely attached infants.

Attachment research has shown the emergence of individual differences in the security of infant-mother attachment during the first year of life as well as their importance for later social-emotional development. A biobehavioral perspective may help settle disagreements about the validity and interpretation of 12-month-old infants' different behavioral patterns of attachment assessed by Ainsworth's Strange Situation. It was shown that, despite less overt distress in insecure-avoidant infants after short separations from the mother, overall cardiac measures indicate arousal patterns similar to the secure infants during separation. However, differences in cardiac response emerged with regard to object versus person orientation during reunion. Additionally, findings of increased cortisol in both insecure-avoidant and disorganized infants support the theoretical interpretation that these infants, in contrast to secure infants, lack an appropriate coping strategy.

Point mutations in the c-Myc transactivation domain are common in Burkitt's lymphoma and mouse plasmacytomas.

We have screened the entire coding region of c-myc in a panel of Burkitt's lymphomas (BLs) and mouse plasmacytomas (PCTs). Contrary to the belief that c-myc is wild type in these tumours, we found that 65% of 57 BLs and 30% of 10 PCTs tested exhibit at least one amino acid (aa) substitution. These mutations were apparently homozygous in all BL cell lines tested and two tumour biopsies, implying that the mutations often occur before Myc/Ig translocation in BL. In PCTs, only the mutant c-myc allele was expressed indicating a functional homozygosity, but occurrence of mutations after the translocation. Many of the observed mutations are clustered in regions associated with transcriptional activation and apoptosis, and in BLs, they frequently occur at sites of phosphorylation, suggesting that the mutations have a pathogenetic role.

Behavioral organization in newborns and its relation to adrenocortical and cardiac activity.

The aim of this study was to assess relations between behavioral organization and adrenocortical and cardiac activity in newborns. Twice during the neonatal period, the behavioral organization of 42 newborns, in terms of orientation and irritability, was assessed by the Neonatal Behavioral Assessment Scale (NBAS), and the newborns' cortisol response to the NBAS procedure was determined. In addition, cardiac activity was assessed during 1 of the NBAS. Whereas there were only inconsistent correlations between newborn irritability and the adrenocortical response during NBAS, low orientation was associated with a higher increase in cortisol in both of the assessments. In addition, orientation was predicted by basal cortisol level. High heart rates were associated with high irritability and low regulation of state, and, in addition, negative relations were indicated between orientation and heart rate variability. The findings support a coping model of biobehavioral relations in newborns.