Blunted cardiac output response to exercise in adolescents born preterm.

PURPOSE: Premature birth is associated with lasting effects, including lower exercise capacity and pulmonary function, and is acknowledged as a risk factor for cardiovascular disease. The aim was to evaluate factors affecting exercise capacity in adolescents born preterm, including the cardiovascular and pulmonary responses to exercise, activity level and strength. METHODS: 21 preterm-born and 20 term-born adolescents (age 12-14 years) underwent strength and maximal exercise testing with thoracic bioimpedance monitoring. Baseline variables were compared between groups and ANCOVA was used to compare heart rate, cardiac output (Q) and stroke volume (SV) during exercise between groups while adjusting for body surface area. RESULTS: Preterm-borns had lower maximal aerobic capacity than term-borns (2.0 ± 0.5 vs. 2.5 ± 0.5 L/min, p = 0.01) and lower maximal power (124 ± 26 vs. 153 ± 33 watts, p < 0.01), despite similar physical activity scores. Pulmonary function and muscular strength did not differ significantly. Although baseline Q and SV did not differ between groups, preterm adolescents had significantly lower cardiac index (Qi) at 50, 75 and 100% of maximal time to exhaustion, driven by SV volume index (SVi, 50% max time: 53.0 ± 9.0 vs. 61.6 ± 11.4; 75%: 51.7 ± 8.4 vs. 64.3 ± 11.1; 100%: 51.2 ± 9.3 vs. 64.3 ± 11.5 ml/m2, all p < 0.01), with similar heart rates. CONCLUSION: Otherwise healthy and physically active adolescents born very preterm exhibit lower exercise capacity than term-born adolescents. Despite similar baseline cardiovascular values, preterm-born adolescents demonstrate significantly reduced Qi and SVi during incremental and maximal exercise.

A novel HLA-B*44 allele, B*4466, discovered in a potential donor for a hematopoietic stem cell transplant.

This report describes the discovery and characterization of the human leukocyte antigen-B*4466 allele.

Discovery of a novel HLA-Cw*08 allele, Cw*0817.

This report describes the discovery and characterization of the HLA-Cw*0817 allele.

Phenomenology of bibliotherapy in modifying teacher punitiveness.

The authors examined the phenomenology of bibliotherapy and its effects in changing preservice teachers' punitive attitudes toward children. Participants (N = 29) were enrolled in a university course (Introduction to Emotional Disturbance). Five books by Torey Hayden, autobiographical accounts of teaching and building relationships with students with emotional and behavioral disorders, were read and discussed within the framework of group bibliotherapy. Participants completed a self-report rating form measuring their tendency toward punitiveness during the first and last weeks of the 15-week semester. Participants also completed a questionnaire measuring the bibliotherapeutic impact of reading Hayden's texts, and they kept journals about the experience of reading Hayden. Comparison of the group's pre- and post-measures on punitiveness showed a small, albeit significant decrease in punitiveness; decreased punitiveness was associated with the therapeutic impact of reading Hayden. Phenomenological analysis of the participants' journal entries revealed that the structure of the experience of reading Hayden was one of identification with the protagonist, leading to emotional and cognitive learning.

The Borderline Syndrome Index: a validation study using the personality assessment schedule.

BACKGROUND: This study examines the validity and screening properties of the Borderline Syndrome Index--BSI (developed in the USA) for categories of the Personality Assessment Schedule--PAS (developed in the UK). METHOD: Patients were recruited by case control sampling. Chance corrected agreement between instruments and screening properties of the BSI were calculated. RESULTS: The BSI proved a moderately sensitive but non-specific screen. Questionnaire scores were highly correlated with symptom measures. CONCLUSIONS: The results do not support the validity of the BSI or its use as a screening instrument. BSI scores may be distorted by current symptoms.

Biological aspects of personality disorder.

A resurgence of interest in the area of personality disorder has been seen in the past 20 years. Researchers have continued along the biological line of investigation working from diverse theoretical standpoints and using increasingly sophisticated approaches. In this review these aspects are set against the background of current debate in the field and placed in their historical context.

Regulation of glucose transport as well as glucose transporter and immediate early gene expression in 3T3-L1 preadipocytes by 8-bromo-cAMP.

In the present study we have examined the ability of 8-bromoadenosine cyclic 3',5'-phosphate (8-bromo-cAMP; the membrane permeant analog of cAMP which can activate protein kinase A) to mimic hormone action and stimulate glucose transport and glucose transporter (GLUT-1) gene expression as well as the expression of several growth-related protooncogenes in quiescent 3T3-L1 fibroblasts. 8-Bromo-cAMP induced a rapid and prolonged increase in the rate of hexose transport. Early activation of hexose transport (within 30 min) was associated with increased plasma membrane immunoreactive glucose transporters, which corresponded to a doubling in the number of D-glucose-displaceable, plasma membrane cytochalasin B binding sites. The time course for 8-bromo-cAMP-induced hexose transport preceded the accumulation of GLUT-1 mRNA, which peaked between 4 and 8 h after exposure to the agent, and subsequently declined to approach basal (control) levels. Expression of the immediate-early genes c-fos and jun-B was induced by 8-bromo-cAMP on a rapid, but sustained time course, whereas induction of c-jun expression was delayed. Alterations in specific mRNAs following exposure to 8-bromo-cAMP were due to increased gene transcription (as judged by nuclear transcription run-on assays), although with respect to GLUT-1, an increase in mRNA stability was also observed. Treatment of the cells with forskolin resulted in the induction of GLUT-1 expression as well as expression of the immediate early genes. Exposure of quiescent 3T3-L1 fibroblasts to 8-bromo-cAMP resulted in a substantial increase in rates of total protein and RNA synthesis, but had little effect on DNA synthesis. The results demonstrate that 8-bromo-cAMP initiated a G0/G1 transition, but did not permit progression into S-phase. The results further suggest that increased cytosolic cAMP results in the stimulation of glucose transport by three distinct mechanisms to include translocation of pre-existing transporters, increased transcription of the GLUT-1 gene and increased stability of GLUT-1 mRNA.

Regulation of glucose transport by tumor necrosis factor-alpha in cultured murine 3T3-L1 fibroblasts.

We have examined the ability of tumor necrosis factor-alpha (TNF) to stimulate hexose transport in 3T3-L1 fibroblasts. Activation of transport occurred in a dose- and time-dependent manner, with maximal stimulation (fourfold) occurring approximately 15 hours after exposure to 2.5 nM TNF. The protein synthesis inhibitor, cycloheximide, blunted TNF-induced 2-deoxyglucose uptake, suggesting that new synthesis was in part responsible for the observed increase. Increased hexose transport occurred concomitant with a 50% increase in general protein synthesis which preceded a fivefold stimulation of thymidine incorporation into DNA. Elevated hexose transport preceded an accumulation of glucose transporter (GLUT-1) mRNA. We have further demonstrated that the early accumulation of GLUT-1 mRNA is accompanied by accumulation of mRNA for both the prootooncogene c-fos as well as that for beta-actin. We suggest that these events represent the pleiotrophic growth factor-like properties of TNF-alpha.

The growth factor-like effects of tumor necrosis factor-alpha. Stimulation of glucose transport activity and induction of glucose transporter and immediate early gene expression in 3T3-L1 preadipocytes.

In the present study, the ability of tumor necrosis factor-alpha (TNF) to stimulate hexose transport in quiescent 3T3-L1 fibroblasts has been examined. Activation of transport occurred in a dose- and time-dependent manner, with maximal stimulation (6-8-fold) observed 16 h after exposure to 2.5 nM TNF. Early activation of hexose transport by TNF (2-fold within 30 min) was associated with increased plasma membrane immunoreactive glucose transporters. Prolonged exposure to TNF (16 h) resulted in a 2-fold increase in glucose transporter content of both plasma and inner membrane compartments. The magnitude of increased glucose transport (6-8-fold) was greater than the increased content of plasma membrane glucose transporters (2-fold), suggesting that the TNF-treatment altered the intrinsic activity of the glucose transporters. Increased transcription of the glucose transporter (GLUT-1) gene, as well as several immediate-early genes (c-fos, c-jun, jun-B, and beta-actin) was observed within 15 min of exposure to TNF. Transcriptional activation of immediate-early genes was tightly coupled to subsequent accumulation of their respective mRNAs. However, increased GLUT-1 mRNA (8 h after TNF treatment) was due to an apparent 3-fold increase in the stability of this message and not to increased transcription. The time course of TNF-induced hexose transport occurred concomitant with a 6-fold increase in total RNA synthesis which preceded a 3-fold increase in protein synthesis. Moreover, TNF induced cell-cycle progression through S-phase, as measured by aphidicolin-sensitive thymidine uptake. Phorbol myristate acetate also stimulated hexose transport as well as expression of the GLUT-1 gene and several immediate-early genes in quiescent 3T3-L1 cells. TNF-induced immediate-early gene expression was intact in PMA-pretreated cells (with the exception of GLUT-1 and beta-actin genes where the response was muted), suggesting the involvement of multiple pathways in TNF signal transduction. Our results indicate that TNF initiates mitogenic events in quiescent 3T3-L1 fibroblasts reminiscent of serum-derived growth factors.

The management and treatment of personality-disordered patients. The use of sequential diagrammatic reformulation.

The clinical management of patients with personality disorders is seldom satisfactory. It is suggested that the bewilderment provoked and experienced by these patients can be reduced by a careful analysis of their shifting states of mind. The construction of diagrams tracing such shifts is helpful to both patients and clinicians. Illustrative case histories are presented.

Multiple pathways for the regulation of ornithine decarboxylase in intestinal epithelial cells.

The regulation of ornithine decarboxylase (ODC) was examined in an intestinal epithelial crypt cell line (IEC-6). Addition of fetal bovine serum or growth factors to quiescent preconfluent cells resulted in a 20- to 30-fold increase in the specific activity of ODC, which was maximal at approximately 4 h. In contrast, ODC mRNA levels either did not change or increased only twofold over the time period examined. The increased enzymatic activity was blocked by cycloheximide, putrescine, and the calmodulin antagonist N-(6-aminohexyl)-5-chloro-1-napthalinesulfonamide (W-7). Cycloheximide alone increased mRNA levels and potentiated the induction in response to serum, suggesting that protein synthesis is not required for the increase in mRNA accumulation. In contrast to its effect on ODC activity, W-7 was without effect on the serum-stimulated increase in ODC or c-fos mRNA levels. Putrescine decreased ODC activity, but not mRNA content, in a dose-dependent manner with an IC50 between 0.1 and 1.0 microM. Also, serum stimulation resulted in a threefold increase in the stability of the enzyme in the presence of cycloheximide; this effect was blocked by pretreatment with W-7. Enzymatic activity was paralleled by ODC protein content as determined by [3H] difluoromethylornithine binding. Finally, the induction of enzyme activity was due entirely to an increase in Vmax as no detectable change in Km for ornithine was detected. These results suggest that ODC is regulated at multiple levels by independent signaling pathways in cultured intestinal epithelial cells. Increased levels of active ODC protein and enzymatic activity are sensitive to W-7 and putrescine.(ABSTRACT TRUNCATED AT 250 WORDS)

Monokine regulation of glucose transporter mRNA in L6 myotubes.

Endotoxin-induced macrophage secretory proteins (monokines) have been shown to stimulate hexose uptake in L6 myotubes (1). In those studies a doubling of the Vmax for hexose uptake was observed which correlated with elevated numbers of glucose transporters (GT) in both plasma and microsomal membranes. To determine if these changes in transporter populations were due to increased GT mRNA, we performed Northern blot analysis using L6 cell RNA and a cDNA to the HepG2 glucose transporter. The L6 myotubes contained a single 2.8 kb species of GT mRNA that increased 2.5-fold after an 8h exposure to the monokine preparation. beta-Actin mRNA levels were unaltered by the treatment, indicating specificity of monokine action. Glucose transporter mRNA content appeared to reach a maximum 8 h after exposure to the monokine. Over the next 16 h the levels of this mRNA gradually decreased, approaching control levels. Data obtained from nuclear transcription run-on assays suggest that increased levels of CT mRNA are due to an increased rate of gene transcription. A second transporter, the insulin-sensitive glucose transporter, was also observed to be expressed in the L6 cells. Monokine treatment resulted in a 60% suppression of the mRNA coding for this protein.

Hair minerals and diet of Prader-Willi syndrome youth.

This study investigated the relationships between mineral elements and Prader-Willi syndrome (PWS) and determined which minerals, if any, separated a group of PWS individuals (N = 19) from a non-PWS mentally retarded control group (N = 60). The PWS group had significantly raised hair magnesium levels and significantly lower hair silicon levels than controls. The PWS group was also elevated in hair calcium, magnesium, and copper in relation to laboratory standards, while their hair silicon, chromium, and lithium levels were deficient in relation to laboratory norms. Discriminant function analysis revealed that by using 16 hair minerals subjects could be correctly classified as PWS or non-PWS with 89.5% and 95.0% accuracy, respectively. It is concluded that continuing research is needed to study the relationship between mineral element patterns and PWS.

Hair-aluminum concentrations and children's classroom behavior.

The study investigated the relationship between children's hair-Al concentrations and children's behavioral performance in school. Hair-Al levels of 102 children drawn from a general school population were correlated with teachers' ratings of the children on the Walker Problem Behavior Identification Checklist (WPBIC). Increasing hair-Al values correlated significantly with increased scores on the WPBIC total scale score. A continuing reexamination of Al exposure in the young is needed in order to determine the margin of safety regarding potentially toxic levels of Al.

Main and interaction effects of metal pollutants on visual-motor performance.

This study investigated possible relationships of metal levels and metal combinations with children's visual-motor performance. Hair-metal concentrations of lead, arsenic, methylmercury, cadmium, and aluminum were determined in 69 randomly selected elementary age children. They were also administered the Bender Visual-Motor Gestalt Test. Parents of subjects were interviewed to control for confounding variables that might affect cognitive development. Regression data indicated that increases in aluminum and the interaction of aluminum with lead were significantly related to decreased visual-motor performance. Because metal levels and metal combinations previously thought harmless may be associated with visual-motor deficits, a continuing reexamination of metal poisoning concentrations is needed.

Main and interaction effects of metallic toxins on classroom behavior.

This study investigated the relationships of metal levels and metal combinations to children's classroom behavior. Hair-metal concentrations of lead, arsenic, mercury, cadmium, and aluminum were determined in 80 randomly selected elementary-age children, who were also rated by their classroom teacher on the Walker Problem Behavior Identification Checklist (WPBIC). Parents were interviewed to control for confounding variables that may have affected behavioral development. Regression analysis indicated that the set of metals was significantly related to increased scores on four of the five WPBIC subscales and on the total scale, with lead being a major contributor to four of the six dependent measures. Metal combinations were significantly related to increased scores on the WPBIC subscales measuring acting-out, disturbed peer relations, and immaturity, and on the total scale. A continuing reexamination of metal poisoning concentrations is needed because metal levels and metal combinations previously thought harmless may be associated with nonadaptive classroom behavior.