Right prefrontal activation produced by arterial baroreceptor stimulation: a PET study.

This study was performed to test the hypothesis of greater right hemispheric involvement in the processing of baroreceptor stimuli. Carotid sinus baroreceptors were stimulated by rhythmically decreasing air pressure in a neck chamber, and under control conditions the thorax was stimulated in a similar manner. Changes in regional cerebral blood flow (rCBF) were measured by PET. Baroreceptor stimulation resulted in rCBF increase in the right anterior-inferior prefrontal cortex (Brodmann areas (BA) 10/44/47) and bilaterally in BA 6/8. We conclude that in at least some stages of baroreceptor information processing the right hemisphere plays a greater role than the left hemisphere.

Reliability of the services assessment for children and adolescents.

OBJECTIVE: This study examined the test-retest reliability of a new instrument, the Services Assessment for Children and Adolescents (SACA), for children's use of mental health services. METHODS: A cross-sectional survey was undertaken at two sites. The St. Louis site used a volunteer sample recruited from mental health clinics and local schools. The Ventura County, California, site used a double-blind, community-based sample seeded with cases of service-using children. Participating families completed the SACA and were retested within four to 14 days. The reliability of service use items was calculated with use of the kappa statistic. RESULTS: The SACA- Parent Version had excellent test-retest reliability for both lifetime service use and previous 12-month use. The SACA also had good to excellent reliability when administered to children aged 11 and older for lifetime and 12-month use. Reliability figures for children aged nine and ten years were considerably lower for lifetime and 12-month use. The younger children's responses suggested that they were confused about some questions. CONCLUSIONS: This study demonstrates that parents and older children can reliably report use of mental health services by using the SACA. The SACA can be used to collect currently unavailable information about use of mental health services.

Specificity of relations between children's control-related beliefs and internalizing and externalizing psychopathology.

The authors examined the specificity of the relation between 3 types of control-related beliefs and internalizing and externalizing psychopathology in a sample of 290 clinic-referred children aged 7 to 17 years. Self-reported beliefs about control (the capacity to cause an intended outcome), contingency (the degree to which a desired outcome can be controlled by a relevant behavior), and competence (an individual's ability to produce the relevant behavior) across 3 domains (academic, behavioral, and social) showed more specific relations with psychopathology than have been previously reported. Among children with externalizing psychopathology, internalizing psychopathology may be specifically associated with increased self-critical awareness about their conduct; externalizing psychopathology may attenuate the specific negative relation between internalizing psychopathology and control-related beliefs in the social domain.

Control-related beliefs and depressive symptoms in clinic-referred children and adolescents: developmental differences and model specificity.

The contingency-competence-control (CCC) model links contingency and competence beliefs to perceived control and, in turn, to depression. However, a developmental perspective suggests that noncontingency may be too abstract a concept to be directly tied to depression before adolescence. We tested the CCC model and this developmental notion, using structural equation modeling, with 360 clinic-referred 8- to 17-year-olds. The CCC model fit the data well for the full sample accounting for 46% of the variance in depression. Separate analyses by age group placed perceived contingency in the best-fit model for adolescents (ages 12-17 years) but not for children (8-11 years). This suggests that abstract cause-effect concepts may have more direct affective impact after the cognitive changes of adolescence (e.g., formal operations) than before. Finally, the CCC model accounted for much more variance in depression than conduct problems, suggesting diagnostic specificity.

Why are we here at the clinic? Parent-child (dis)agreement on referral problems at outpatient treatment entry.

Do clinic-referred children and their parents agree on the problems for which treatment is undertaken? The authors asked 381 outpatient-clinic-referred children and their parents to list, independently, the child's target problems. Of the parent-child pairs, 63% failed to agree on even a single problem. When problems were grouped into broad categories (e.g., delinquent, withdrawn), more than a third of the pairs still failed to agree on a single broad problem area. Parent-child agreement was higher for externalizing than for internalizing problem categories (though poor for both). Low parent-child agreement may help explain the poor outcomes often reported for clinic-based child therapy.

Child and adolescent psychotherapy in research and practice contexts: review of the evidence and suggestions for improving the field.

The body of evidence on child and adolescent psychotherapy outcomes has now grown to more than 500 studies. Here we summarize key findings, focusing on effectiveness and efficacy research. Research is sparse on the effectiveness of treatment in everyday practice, but available evidence suggests little benefit. By contrast, extensive research on efficacy of structured treatments administered under controlled conditions shows very substantial evidence of benefit. We note several specific treatments for which evidence is encouraging, and we offer suggestions for future research. Particularly important will be research on treatment models most often used in practice settings, tests of outcome mediators and moderators, tests employing a broadened range of treatment delivery models, and research bridging the gap between lab-tested treatments and the conditions of real-world practice.

The development of close relationships in Japan and the United States: paths of symbiotic harmony and generative tension.

Findings from research on parent-child and adult mate relationships suggest that there are different paths of development in Japan and the United States. In Japan, the path is one of symbiotic harmony, as seen in the emphasis on union in infancy, others' expectations in childhood, the stability of relationships with parents and peers in adolescence, and assurance about the mate relationship in adulthood. In the United States, the path is one of generative tension, as seen in the tug between separation and reunion in infancy, the emphasis on personal preferences in childhood, the transfer of closeness from parents to peers in adolescence, and the emphasis on trust-a faith and hope in new relationships-in adulthood. The notion that there are different paths of development challenges Western investigators' presumption that certain processes-separation-individuation, use of the relational partner as a secure base for exploration, and conflict between partners-are central in all relationships. The notion of different paths also challenges the assumption of many cross-cultural investigators that relationships in the United States are less valued or weaker than those in Japan; this article highlights cultural differences in the meaning and dynamics, as opposed to the importance and strength, of relationships. The model suggests a need to investigate the processes underlying, and the adaptive consequences of, these two alternative paths.

Trade-offs in the study of culture and development: theories, methods, and values.

The commentators are unanimous in their support for our general orientation to culture and development, and for the pathways we have identified, and they suggest ways to enrich our approach to theory, methods, and values. We view their main suggestions as relating to trade-offs: between theories that highlight generalizations or exceptions; between methods that rely on one-, two-, or multiculture studies; and between values involving individuation or accommodation. Here, we describe ways to find an optimal balance in each instance.

Deletion analysis defines distinct functional domains for protein-protein and nucleic acid interactions in the ORF1 protein of mouse LINE-1.

LINE-1, or L1, is a non-LTR retrotransposon in mammals. Retrotransposition of L1 requires the action of two element-encoded proteins, ORF1p and ORF2p. ORF2p provides essential enzymatic activities for the reverse transcription and integration of a newly transposed copy of L1, whereas the exact role of ORF1p is less well understood. The 43 kDa ORF1p copurifies as a large complex with L1 RNA in extracts of human and mouse cells. Mouse ORF1p purified from Escherichia coli binds RNA and single-stranded DNA in vitro, exhibits nucleic acid chaperone activity, and is capable of protein-protein interaction. In this study we create a series of deletions in the ORF1 sequence, express the truncated proteins and examine their activities to delineate the region of ORF1p responsible for these different functions. By both yeast two-hybrid analysis and GST pull-down assay, the protein-protein interaction domain is defined as a coiled-coil domain that encompasses about one third of the protein near its N terminus. Based on data obtained with UV-cross-linking, electrophoretic mobility-shift assay and an annealing assay, the C-terminal one third of ORF1p is both necessary and sufficient for nucleic acid binding and to promote annealing of complementary oligonucleotides. Separation of these activities into different domains of ORF1p will facilitate detailed biochemical analyses of the structure and function of this protein and understanding of its role during L1 retrotransposition.

Attachment and culture. Security in the United States and Japan.

Attachment theorists maintain that cultural differences are relatively minor, and they focus on universals. Here the authors highlight evidence of cultural variations and note ways in which attachment theory is laden with Western values and meaning. Comparisons of the United States and Japan highlight the cultural relativity of 3 core hypotheses of attachment theory: that caregiver sensitivity leads to secure attachment, that secure attachment leads to later social competence, and that children who are securely attached use the primary caregiver as a secure base for exploring the external world. Attachment theorists use measures of sensitivity, competence, and secure base that are biased toward Western ways of thinking: The measures emphasize the child's autonomy, individuation, and exploration. In Japan, sensitivity, competence, and secure base are viewed very differently, calling into question the universality of fundamental tenets of attachment theory. The authors call for an indigenous approach to the psychology of attachment.

Estrogen metabolism by conjugation.

The involvement of estrogens in carcinogenic processes within estrogen-responsive tissues has been recognized for a number of years. Classically, mitogenicity associated with estrogen receptor-mediated cellular events was believed to be the mechanism by which estrogens contributed to carcinogenesis. Recently, the possibility that estrogens might contribute directly to mutagenesis resulting from DNA damage has been investigated. That damage is apparently a result of the formation of catechol estrogens that can be further oxidized to semiquinones and quinones. Those molecules represent reactive oxygen species and electrophilic molecules that can form depurinating DNA adducts, thus having the potential to result in permanent nucleotide mutation. Conjugation of parent estrogens to sulfate and glucuronide moieties; of catechol estrogens to methyl, sulfate, and glucuronide conjugates; and of catechol estrogen quinones to glutathione conjugates all represent potential "detoxification" reactions that may protect the cell from estrogen-mediated mitogenicity and mutagenesis. In this chapter, the biochemistry and molecular genetics of those conjugative reaction pathways are discussed. When applicable, the involvement of specific enzymatic isoforms is presented. Finally, the activity of many of these conjugative biotransformation reactions is subject to large interindividual variation--often due to the presence of common nucleotide polymorphisms within the genes encoding those enzymes. Functionally significant genetic polymorphisms that might contribute to variable conjugation of estrogens and catechol estrogens are also discussed.

The Service Assessment for Children and Adolescents (SACA): adult and child reports.

OBJECTIVE: To describe differences in parent-child responses to the Service Assessment for Children and Adolescents (SACA). METHOD: Studies were done at UCLA and Washington University based on service-using and community subjects drawn from community households or public school student lists, respectively. Results are presented for 145 adult-youth pairs in which the youth was 11 or older. RESULTS: The SACA adult-youth correspondence for lifetime use of any services, inpatient services, outpatient services, and school services ranged from fair to excellent (kappa = 0.43-0.86, with most at 0.61 or greater). Similarly, the SACA showed a good to excellent correspondence for services that had been used in the preceding year (kappa = 0.45-0.77, with most greater than 0.50). The parent-youth correspondence for use of specific service settings in the above generic categories ranged from poor to excellent (kappa = 0.25-0.83, with half at 0.50 or greater). CONCLUSIONS: The SACA has better adult-youth correspondence than any service use questionnaire with published data, indicating that both adult and youth reports are not needed for all research on mental health services. This is especially encouraging news for researchers working with high-risk youth populations, in which a parent figure is often not available.

Nuclear localization of catechol-O-methyltransferase in neoplastic and nonneoplastic mammary epithelial cells.

Catechol-O-methyltransferase (COMT) plays both a regulatory and protective role in catechol homeostasis. It contributes to the regulation of tissue levels of catecholamines and catecholestrogens (CEs) and, by blocking oxidative metabolism of catechols, prevents endogenous and exogenous catechols from becoming a source of potentially mutagenic electrophiles. Evidence implicating CEs in carcinogenesis, in particular in the hamster kidney model of estrogen-induced cancer, has focused attention on the protective role of COMT in estrogen target tissues. We have previously reported that treating hamsters with estrogens causes translocation of COMT to nuclei of epithelial cells in the renal cortex, the site of CE biosynthesis and where the cancers arise. This finding suggested that nuclear COMT may be a marker of a threat to the genome by catechols, including CEs. It is postulated that CEs play a role in the genesis of breast cancer by contributing to a state of chronic oxidative stress that is presumed to underlie the high incidence of this disease in the United States. Therefore, here we used immunocytochemistry to re-examine human breast parenchyma for nuclear COMT. In addition to confirming previous reports of cytoplasmic COMT in mammary epithelial cells, we identified nuclear COMT in foci of mammary epithelial cells in histologically normal breast tissue of virtually all control (macromastia) and cancer patients and in breast cancer cells. There was no correlation between tissue histology and the numbers of cells with nuclear COMT, the size of foci containing such cells, or intensity of nuclear COMT immunostaining. The focal nature of the phenomenon suggests that nuclear COMT does not serve a housekeeping function but that it reflects a protective response to an increased local catechol load, presumably of CEs and, as such, that it may be a characteristic of the population of women studied who share the same major risk factor for developing breast cancer, that of living in the industrialized West.

Expression of BAX in plasma cell dyscrasias.

Several studies demonstrate that the BCL-2 and BCL-XL antiapoptotic genes are variably expressed in plasma cells of patients with multiple myeloma (MM). However, the plasma cell expression of BAX protein, their major proapoptotic partner, has not been investigated. Our initial Western blot analysis of myeloma cell extracts also suggested patient variability in the expression of BAX, which was not altered by exposure to interleukin 6. To further investigate the significance of BAX expression, we performed immunohistochemistry on archival bone marrow biopsies and compared BAX staining to BCL-2 immunostaining. Expression was first evaluated in 104 patients with reactive plasmacytosis, monoclonal gammopathy of undetermined significance/smoldering MM, or active MM. An increase (P < 0.05) in expression of both BAX and BCL-2 was detected in MM patients compared with patients with reactive plasmacytosis. Patients with monoclonal gammopathy of undetermined significance/smoldering MM had intermediate values. For correlations with outcome, expression was assessed in 43 patients at diagnosis who were treated with melphalan and prednisone; 30 at diagnosis who were treated with vincristine, Adriamycin, and dexamethasone; and 29 at relapse who were treated with second-line therapy. There was no correlation between BAX or BCL-2 expression and response to chemotherapy or duration of response or between BCL-2 expression and survival. However, patients who demonstrated extremely low plasma cell BAX expression had significantly increased survival. This was true for patients initially treated with melphalan and prednisone or vincristine, Adriamycin, and dexamethasone, as well as patients studied at relapse. BAX expression did not correlate with expression of proliferating cell nuclear antigen used as a marker of proliferation. These data indicate a myeloma-specific increase in BAX expression in plasma cells and suggest that low BAX expression identifies a cohort of patients with long survival, which is not specifically associated with low proliferating cell nuclear antigen expression.

GMx33: a novel family of trans-Golgi proteins identified by proteomics.

The known functions of the Golgi complex include the sorting, packaging, post-translational modification, and transport of secretory proteins, membrane proteins, and lipids. Other functions still remain elusive to cell biologists. With the goal of identifying novel Golgi proteins, a proteomics project was undertaken to map the major proteins of the organelle using two-dimensional gels, to identify the unknowns using tandem mass spectrometry, and to screen for Golgi residents using GFP-fusion constructs. Multiple unknowns were identified, and the initial characterization of one of these proteins is reported here. GMx33 alpha is a member of a conserved family of cytosolic Golgi-associated proteins with no known homology to any known functional domain or protein. Biochemical analyses show that GMx33 alpha differentially partitions into all phases of multiple detergent extractions, and two-dimensional immunoblots reveal that there are multiple differentially modified forms of GMx33 alpha associated with the Golgi, several of which are phosphorylated. Evidence suggests that these post-translational modifications regulate its association with the Golgi. GMx33 alpha was not found on Golgi budded vesicles, and immuno-electron microscopy co-localizes GMx33 alpha to the trans-face on the same three cisternae as TGN38 in normal rat kidney cells. This work represents the preliminary characterization of a novel family of trans-Golgi-associated proteins.

Can we trust parent reports in research on cultural and ethnic differences in child psychopathology? Using the bicultural family design to test parental culture effects.

Research comparing cultural and ethnic groups on child psychopathology has relied heavily on parent reports. But don't parents' own cultural backgrounds bias their reports, undermining valid assessment of actual child behavior? The question is hard to address because parent and child culture tend to be confounded. To solve this problem, we assembled an unusual but heuristically valuable sample: 50 bicultural families, each with an ethnic Thai parent reared in Thailand and a Caucasian parent reared in the U.S. Parents in each pair independently completed standardized problem checklists on the same child in their family. Across all 10 empirically derived problem syndromes, no parental culture effect was either significant or larger than "small," by Cohen's (1988) standards; across all 140 specific problems, the mean percent of variance accounted for by parent culture was less than 1%. Results do not point to a biasing effect of parental culture.

Allogenic fetal retinal pigment epithelial cell transplant in a patient with geographic atrophy.

PURPOSE: To test the hypothesis that healthy fetal retinal pigment epithelium (RPE) can rescue the remaining viable RPE and choriocapillaries and thereby the photoreceptors in non-neovascular age-related macular degeneration (ARMD) (geographic atrophy [GA]). METHODS: A 65-year-old legally blind woman with non-neovascular ARMD underwent fetal RPE transplantation. Best-corrected visual acuity testing, detailed fundus examination, fundus photography, fluorescein angiography, scanning laser ophthalmoscope macular perimetry, and humoral and cellular immune response testing were performed. A suspension of RPE was infused into the subretinal space through a retinotomy along the superotemporal arcade at the edge of the area of GA. The patient did not take systemic immunosuppressants. RESULTS: The patient's vision remained unchanged for 5 months after the surgery. Fluorescein angiography after transplantation showed leakage and staining at the level of the outer retina. There was progressive subretinal fibrosis in the area of the transplant. Immune response studies showed a weakly positive mixed lymphocyte response against phosducin and rhodopsin. CONCLUSION: Although it is surgically feasible to transplant fetal RPE to the subretinal space of patients with GA, such an allogenic RPE transplant without immunosuppression leads to leakage on fluorescein angiography and eventual fibrosis. A very weak immune response against proteins associated with photoreceptors is also of concern.