Human placental cytotrophoblasts produce the immunosuppressive cytokine interleukin 10

The mechanism by which the mammalian mother accepts the implanting fetus as an allograft remains unexplained, but is likely to be the result of a combination of factors. Mononuclear cytotrophoblasts, the specialized fetal cells of the placenta that invade the uterus, play an important role. These cells express HLA-G, an unusual major histocompatibility complex class I-B molecule, and secrete cytokines and pregnancy-specific proteins that can regulate immune function. We investigated whether cytotrophoblasts secrete interleukin 10 (IL-10), a cytokine that potently inhibits alloresponses in mixed lymphocyte reactions. Cytotrophoblasts from all stages of pregnancy produced IL-10 in vitro, but neither placental fibroblasts nor choriocarcinoma (malignant trophoblast) cell lines did so. Spontaneous IL-10 production averaged 650, 853, and 992 pg/10(6) cells in the first, second, and third trimesters of pregnancy, respectively. IL-10 secretion dropped approximately 10-fold after the first 24 h of culture, and was paralleled by a decrease in messenger RNA. IL-10 messenger RNA was detected in biopsies of the placenta and the portion of the uterus that contains invasive cytotrophoblasts, suggesting that this cytokine is also produced in vivo. IL-10 secreted by cytotrophoblasts in vitro is bioactive, as determined by its ability to suppress interferon gamma production in an allogeneic mixed lymphocyte reaction. We conclude that human cytotrophoblast IL-10 may be an important factor that contributes to maternal tolerance of the allogeneic fetus.     

Proton MR spectroscopy after acute central nervous system injury: outcome prediction in neonates, infants, and children

PURPOSE: To evaluate the usefulness of proton magnetic resonance (MR) spectroscopy in predicting 6-12-month neurologic outcome in children after central nervous system injuries. MATERIALS AND METHODS: Localized single-voxel, 20-msec-echo-time MR spectra (including N-acetylaspartate [NAA], choline [Ch], creatine and phosphocreatine [Cr]) were obtained in the occipital gray matter in 82 patients and 24 control patients. Patient age groups were defined as neonates (< or = 1 month [n = 23]), infants (1-18 months [n = 31]), and children (> or = 18 months [n = 28]). Metabolite ratios and the presence of lactate were determined. Linear discriminant analysis-with admission clinical data, proton MR spectroscopy findings, and MR imaging score (three-point scale based on severity of structural neuroimaging changes)-was performed to help predict outcome in each patient. Findings were then compared with the actual 6-12-month outcome assigned by a pediatric neurologist. RESULTS: Outcome on the basis of proton MR spectroscopy findings combined with clinical data and MR imaging score was predicted correctly in 91% of neonates and in 100% of infants and children. Outcome on the basis of clinical data and MR imaging score alone was 83% in neonates, 84% in infants, and 93% in children. The presence of lactate was significantly higher in patients with poor outcome than in patients with good-moderate outcomes in all three age groups (neonates, 38% vs 5%; infants, 87% vs 5%; children, 64% vs 10% [chi 2 test, P < .02]). In children with poor outcomes, NAA/Cr ratios were significantly lower in infants (P = .006) and children (P < .001), and NAA/Ch ratios were significantly lower in infants (P = .001) and neonates (P = .05). CONCLUSION: Findings at proton MR spectroscopy helped predict long-term neurologic outcomes in children after central nervous system injury.     

Latent transforming growth factor-beta binding protein domains involved in activation and transglutaminase-dependent cross-linking of latent transforming growth factor-beta

Transforming growth factor-beta (TGF-beta) is secreted by many cell types as part of a large latent complex composed of three subunits: TGF-beta, the TGF-beta propeptide, and the latent TGF-beta binding protein (LTBP). To interact with its cell surface receptors, TGF-beta must be released from the latent complex by disrupting noncovalent interactions between mature TGF-beta and its propeptide. Previously, we identified LTBP-1 and transglutaminase, a cross-linking enzyme, as reactants involved in the formation of TGF-beta. In this study, we demonstrate that LTBP-1 and large latent complex are substrates for transglutaminase. Furthermore, we show that the covalent association between LTBP-1 and the extracellular matrix is transglutaminase dependent, as little LTBP-1 is recovered from matrix digests prepared from cultures treated with transglutaminase inhibitors. Three polyclonal antisera to glutathione S-transferase fusion proteins containing amino, middle, or carboxyl regions of LTBP-1S were used to identify domains of LTBP-1 involved in cross-linking and formation of TGF-beta by transglutaminase. Antibodies to the amino and carboxyl regions of LTBP-1S abrogate TGF-beta generation by vascular cell cocultures or macrophages. However, only antibodies to the amino-terminal region of LTBP-1 block transglutaminase-dependent cross-linking of large latent complex or LTBP-1. To further identify transglutaminase-reactive domains within the amino-terminal region of LTBP-1S, mutants of LTBP-1S with deletions of either the amino-terminal 293 (deltaN293) or 441 (deltaN441) amino acids were expressed transiently in CHO cells. Analysis of the LTBP-1S content in matrices of transfected CHO cultures revealed that deltaN293 LTBP-1S was matrix associated via a transglutaminase-dependent reaction, whereas deltaN441 LTBP-1S was not. This suggests that residues 294-441 are critical to the transglutaminase reactivity of LTBP-1S.     

Cost effectiveness of inpatient initiation of antiarrhythmic therapy for supraventricular tachycardias

This study assessed the cost effectiveness of inpatient antiarrhythmic therapy initiation for supraventricular tachycardias using a metaanalysis of proarrhythmic risk and a decision analysis that compared inpatient to outpatient therapy initiation. A MEDLINE search of trials of antiarrhythmic therapy for supraventricular tachycardias was performed, and episodes of cardiac arrest, sudden or unexplained death, syncope, and sustained or unstable ventricular arrhythmias were recorded. A weighted average event rate, by sample size, was calculated and applied to a clinical decision model of therapy initiation in which patients were either hospitalized for 72 hours or treated as outpatients. Fifty-seven drug trials involving 2,822 patients met study criteria. Based on a 72-hour weighted average event rate of 0.63% (95% confidence interval, 0.2% to 1.2%), inpatient therapy initiation cost $19,231 per year of life saved for a 60-year-old patient with a normal life expectancy. Hospitalization remained cost effective when event rates and life expectancies were varied to model hypothetical clinical scenarios. For example, cost-effectiveness ratios for a 40-year-old without structural heart disease and a 60-year-old with structural heart disease were $37,510 and $33,310, respectively, per year of life saved. Thus, a 72-hour hospitalization for antiarrhythmic therapy initiation is cost effective for most patients with supraventricular tachycardias.     

Extracardiac conduit Fontan procedure without cardiopulmonary bypass

There are a number of potential advantages of extracardiac conduit cavopulmonary anastomosis for palliation of functional single ventricle heart disease, including the ability to perform the operation with no aortic cross-clamping and with minimal duration of extracorporeal circulation. In many patients, it may be possible to perform the procedure without cardiopulmonary bypass altogether. In this report, we present our technique for performing the extracardiac conduit Fontan operation without cardiopulmonary bypass.     

From Boys Town to Oliver Twist: Separating fact from fiction in welfare reform and out-of-home placement of children and youth.

Recent debate following the suggestion to place children of "welfare mothers" in "orphanages" illustrates the need to evaluate the relative goodness of residential care and to examine many of the basic assumptions underlying current welfare reform proposals. Nearly half a million children and youth are currently in government-funded out-of-home care in the United States. As custodians of this challenging population, child and youth care workers are neither parents nor therapists, but appear to perform both of these roles as "therapeutic parents." Two comprehensive and mature literatures—common factors of therapist efficacy and parental correlates of offspring psychopathology—provide theoretical and empirical support for this model of child and youth care. Current welfare reform proposals are evaluated in the context of the therapeutic parent model; assumptions about welfare mothers are also examined. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Age, education, and the internal consistency of personality scales.

Investigated whether the internal consistencies of personality scales increase with age and education and, if so, what causes these increases. Between 96 and 106 respondents in each of the age groups 13–24 yrs, 15–26 yrs, 17–28 yrs, and 19–20 yrs and 198 adults (aged 21–25 yrs) with varying amounts of formal education completed the Taylor Manifest Anxiety Scale, the California F-Scale, the Marlowe-Crowne Social Desirability Scale, a dogmatism scale, the Extraversion subscale of the Eysenck Personality Inventory, a self-monitoring scale, and a private self-conscious scale. Results show that age and education were both linearly related to the internal consistency with which Ss responded to all 8 personality scales. The relations were stronger for education than for age, the correlations between individuals' consistency scores across scales revealed a strong consistency response set. Stepwise regression showed that this internal consistency was related to age, education, the failure to understand items, and private self-consciousness. These last 2 contributions suggest that lower consistencies are partly a measurement problem and partly due to real lower personality consistencies on trait constructs. It is suggested that, because most personality research has used nonadults, the lower internal consistency of the younger Ss has contributed to the limited predictive power of personality scales. (35 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)