Regulation of mRNA expression encoding chaperone and co-chaperone proteins of the glucocorticoid receptor in peripheral blood: association with depressive symptoms during pregnancy.

BACKGROUND: Major depressive disorder during pregnancy associates with potentially detrimental consequences for mother and child. The current study examined peripheral blood gene expression as a potential biomarker for prenatal depressive symptoms. METHOD: Maternal RNA from whole blood, plasma and the Beck Depression Inventory were collected longitudinally from preconception through the third trimester of pregnancy in 106 women with a lifetime history of mood or anxiety disorders. The expression of 16 genes in whole blood involved in glucorticoid receptor (GR) signaling was assessed using real-time polymerase chain reaction. In parallel, plasma concentrations of progesterone, estradiol and cortisol were measured. Finally, we assessed ex vivo GR sensitivity in peripheral blood cells from a subset of 29 women. RESULTS: mRNA expression of a number of GR-complex regulating genes was up-regulated over pregnancy. Women with depressive symptoms showed significantly smaller increases in mRNA expression of four of these genes - FKBP5, BAG1, NCOA1 and PPID. Ex vivo stimulation assays showed that GR sensitivity diminished with progression of pregnancy and increasing maternal depressive symptoms. Plasma concentrations of gonadal steroids and cortisol did not differ over pregnancy between women with and without clinically relevant depressive symptoms. CONCLUSIONS: The presence of prenatal depressive symptoms appears to be associated with altered regulation of GR sensitivity. Peripheral expression of GR co-chaperone genes may serve as a biomarker for risk of developing depressive symptoms during pregnancy. The presence of such biomarkers, if confirmed, could be utilized in treatment planning for women with a psychiatric history.

Identification of tubulin in Dictyostelium discoideum: characterization of some unique properties.

We used three antitubulin antibodies to localize Dictyostelium tubulin subunits on two-dimensional polyacrylamide gels by Western blotting. All three antibodies, a polyclonal antibody against sea urchin alpha- and beta-tubulin and two monoclonal antibodies against yeast alpha-tubulin, recognize the same set of polypeptides with a molecular weight of 55,000 while focusing at a pH far more basic than all other tubulins. Each antibody specifically stains the microtubule system of slime mold amoebae by indirect immunofluorescence. The microtubule system can be isolated as a major component of the amoeba cytoskeleton, and these preparations are greatly enriched for the presumptive tubulin subunits. The microtubules of these cytoskeletons are resistant to being depolymerized by millimolar concentrations of calcium, while they retain their cold sensitivity. Comparison of peptide maps of slime mold and brain alpha-tubulins indicates that the proteins are related but not identical. Possible explanations for these unusual characteristics are discussed.

Use of Nystatin-Resistant Mutations in Parasexual Genetic Analysis in DICTYOSTELIUM DISCOIDEUM.

Nystatin-resistant mutations exhibit extreme sensitivity to 1.3 mm coumarin. The mutations fall into three complementation groups so it is possible to select for nonallelic mutations conferring sensitivity to coumarin by selection on nystatin-containing nutrient agar plates. Complementation between such coumarin-sensitive mutations allows the selection of diploids on coumarin-containing nutrient agar. Two of the nystatin resistance genes, nysB and nysC, have been mapped tentatively to the previously unmarked linkage group V.

Anticipatory nausea and vomiting in pediatric cancer patients.

The purpose of this study was to determine the prevalence and correlates of anticipatory nausea and vomiting in a sample of pediatric patients with cancer who were receiving outpatient chemotherapy. Forty male and female patients representing a broad range of diagnoses were interviewed with their parents concerning nausea and vomiting before and after chemotherapy. Anticipatory nausea was reported by 28.8% of the sample; anticipatory vomiting was present in 20% of the sample. An additional 9% had experienced anticipatory nausea and vomiting in the past but not currently. Anticipatory nausea and vomiting was positively correlated with the emetic potential of chemotherapeutic regimens and the severity of nausea and vomiting after chemotherapy; anticipatory nausea and vomiting most often developed within the first 4 months of treatment. Onset of anticipatory nausea and vomiting usually occurred two to four hours before treatment and was most severe at the actual time of drug administration. Considerable interpatient variability was observed, with treatment-related factors accounting for only 22% of the variance in the occurrence of anticipatory nausea and vomiting. These findings are considered within a behavioral framework for understanding conditioned aversions in pediatric patients with cancer. Implications for patient education, future research on the prediction of children at risk, and intervention are discussed.

Behavioral distress in pediatric patients with cancer receiving chemotherapy.

The purpose of this study was to assess prospectively the behavioral effects of chemotherapy in children and adolescents with cancer. A total of 94 patients, with a range of malignancies and chemotherapy protocols, were evaluated 1, 4, and 7 months after treatment initiation. Assessments focused on behavioral distress symptoms and nausea/vomiting experienced in anticipation of chemotherapy and following its administration. Significant disturbances were described in a variety of domains, with adolescents exhibiting consistently higher levels of behavioral symptoms and nausea/vomiting than younger children. Behavioral distress tended to decrease and stabilize throughout time for children and to increase throughout time for adolescents. Age differences in behavioral distress were independent of the emetogenicity of therapy given to younger and older patients. The interaction of biologic and psychosocial factors in determining treatment-related distress is discussed, along with implications for future predictive and intervention studies.

Ruptured mycotic aortic aneurysm.

A right flank mass, in a patient with fever of unknown origin, pain, and superiorly displaced right kidney on excretory urogram, was explored through a subcostal incision. Finding of a retroperitoneal abscess was anticipated; instead of a ruptured mycotic aortic aneurysm was encountered. An awareness that entities such as this may exist is imperative in the differential diagnosis of flank masses. Treatment through a flank incision presents an elusive if not impossible feat. Because of the gravity of the underlying disease, misdiagnosis almost always results in death.

Alteration of memory in the reduction of children's distress during repeated aversive medical procedures.

The present study sought to reduce children's distress during aversive medical procedures using a brief, cost-effective intervention aimed at reframing memory. Fifty children diagnosed with leukemia (25 treatment, 25 attention control, aged 3-18) were observed as they underwent 3 consecutive lumbar punctures (LPs; baseline, postintervention, and follow-up). Self-report, physiological, and observable distress measures were collected before and after each LP. At posttreatment, children in the intervention group showed reductions in anticipatory physiological and self-report ratings relative to the control group. At follow-up, these effects generalized to reductions in procedural distress. These results suggest that (a) a simple memory-based intervention is efficacious at reducing children's distress and (b) benefits from this intervention are maintained over 1 week even without continued intervention.

Conditioned aversions in pediatric cancer patients receiving chemotherapy.

Pediatric cancer patients experiencing nausea/vomiting in anticipation of chemotherapy were studied in comparison to a matched group of patients with no history of anticipatory nausea/vomiting (ANV). Patients with ANV were characteristically more anxious and tended to screen sensory information less selectively than patients without ANV. Parents of patients with ANV relied more heavily on threat of punishment and less on modeling and reassurance when managing their children in fearful situations than did parents of patients with no ANV. ANV was related to an increased incidence of experimentally conditioned taste aversions. The contribution of patient variables to the prediction of ANV and implications for research are discussed.

Perceived social support and adjustment of children with newly diagnosed cancer.

The negative impact on psychologic adjustment from the stress of living with newly diagnosed cancer is hypothesized to be affected by perceived social support. Thirty children with newly diagnosed cancer completed standardized assessment instruments measuring depressive symptoms, state anxiety, trait anxiety, social anxiety, general self-esteem, and perceived social support from classmates, parents, teachers, and friends. Their parents completed a standardized assessment instrument measuring internalizing and externalizing behavior problems. Perceived classmate, parent, and teacher social support were variously correlated with the psychologic adjustment parameters in the hypothesized direction of greater support predicting lower psychologic distress and higher self-esteem. Hierarchical multiple regression analyses identified perceived classmate social support as the most consistent predictor of adaptation, providing further evidence of the essential function of the social environment of the school setting in affecting the adjustment of children with newly diagnosed cancer.

Cognitive functioning in long-term survivors of childhood leukemia: a prospective analysis.

Treatment-related cognitive impairments have been reported for survivors of childhood leukemia following prophylactic central nervous system (CNS) treatment with 2400 cGy craniospinal irradiation and intrathecal chemotherapy. The present study was designed to prospectively evaluate cognitive functioning of 24 children prior to CNS prophylaxis of 1800 cGy of craniospinal irradiation and intrathecal drugs, and at intervals of 1 and 4-5 years. At diagnosis, prior to CNS treatment, all 24 subjects performed in the average range of intelligence, as measured by the Wechsler Intelligence Scales. Subjects continued to perform in the average range with no significant declines at the 1-year follow-up. Significant declines in cognitive functioning, however, were found at the 4- to 5-year follow-up period, with five subjects (21%) performing in the low average or borderline levels of intelligence. Of the 19 subjects performing in the average range, five showed significant discrepancies between Verbal and Performance IQ scores. Nine subjects exhibited poor performance on a subtest cluster assessing perceptual and attentional processes. With regard to school experiences, 50% of the subjects had received some type of special education services. The findings indicate the need for annual evaluations of cognitive functioning in long-term survivors of childhood leukemia who received 1800 cGy craniospinal irradiation, to identify potential cognitive late effects of treatment requiring appropriate special education services.

Memory for spatial location in retarded and nonretarded persons.

Item memory and memory for spatial location were examined in college students, mildly retarded persons and moderately retarded persons. They performed under semantic or nonsemantic encoding instructions to remember pictures presented in a large book. Recall and relocation (unexpected) tests followed immediately after studying the pictures and, again, 24 h later. Mildly retarded persons were deficient in memory for items (effortful processing), but not in memory for location (automatic processing). Moderately retarded persons were deficient in both types of memory. Additionally, there were IQ-related differences in the long-term memory of location information, as well as item information. Location memory, as opposed to item memory, was shown to be (1) sensitive to encoding instruction, (2) insensitive to differences in intelligence, and (3) more sensitive to long-term forgetfulness.

Social support and social cognitive problem-solving in children with newly diagnosed cancer.

Children newly diagnosed with cancer have been documented to be at increased risk for difficulties in their return to school and ongoing positive social experiences. This article reviews the critical role of social support in helping children adjust to their illness and treatment. Social skills training for newly diagnosed children is presented as an important intervention strategy for increasing positive social interactions and overall psychosocial adjustment. A randomized, clinical research trial currently in progress that will evaluate the impact of social skills training on newly diagnosed children 5-13 years of age is delineated. The potentially positive impact of social skills training on the prevention of emotional problems and increased biologic survival are discussed.

Altered prestarvation response in a nystatin resistant Dictyostelium discoideum mutant.

Wild-type Dictyostelium amoebae secrete an autocrine, prestarvation factor (PSF) that allows them to measure the amount of food bacteria compared to their cell density. When the ratio of PSF to bacteria reaches a threshold, the cells are signaled to prepare for eventual starvation. This prestarvation response (PSR) usually starts three to four generations before the end of exponential growth, leading to the accumulation of several aggregation specific genes during growth. We characterize a nystatin-resistant mutant, HK19, that expresses the PSR genes three generations earlier than wild type but has an otherwise wild-type PSR. Although HK19 has a full PSR during growth, HK19 continues to grow at the wild-type rate and reaches normal cell densities. Because HK19 temporally separates the PSR from starvation, it became possible to test whether starvation is required for development. Since HK19 growing at low density can be induced to clump with either cAMP or folate, it appears that the PSR and an external signal are sufficient for entry into development. These data suggest that the PSR is a complex genetic pathway that induces genes involved in the exit from growth and the entry into development.

Parasexual recombination in Dictyostelium discoideum: selection of stable diploid heterozygotes and stable haploid segregants (clones-temperature sensitive-ploidy-fruiting bodies-spore-slime mold).

Haploid strains of Dictyostelium discoideum bearing temperature-sensitive mutations have been used to select stable diploid, heterozygotic clones, which arise at low frequency (about 10(-5)). Segregants arise from such diploids at low frequency (about 10(-3)). The diploids were heterozygous for resistance to cycloheximide and were phenotypically sensitive to the drug. Growth of the diploid cells in the presence of cycloheximide automatically selected those segregants bearing the resistant allele, and facilitated examination of the assortment of unselected markers. The combination of the two selective methods provides a workable system of genetic analysis in this species. We have used this method to locate six markers on three different linkage groups.