Motion analysis of a child with Niemann-Pick disease type C treated with miglustat.

Niemann-Pick disease type C (NPC) is a progressive neurodegenerative disorder for which there is no effective treatment other than supportive therapy. Recently, the oral medication miglustat has been offered as a possible therapy aimed at reducing pathological substrate accumulation. This article describes the use of computerized three-dimensional motion analysis to evaluate a 3-year-old child with NPC treated with miglustat for 12 months.

Childhood behavioral inhibition and maternal symptoms of depression.

Background: The significance of behavioral inhibition in the second year of life for the development of social phobia in later childhood was the incentive to explore whether maternal postnatal psychopathology is a predictor for behavioral inhibition in the offspring.

Method: 101 mother-infant pairs were recruited from local obstetric units and examined for maternal psychopathology by the Symptom Checklist and the Edinburgh Postnatal Depression Scale several times during the first postnatal year. Child behavioral inhibition was assessed at 14 months in a laboratory procedure.

Towards Clinical Application of Methylated DNA Sequences as Cancer Biomarkers: A Joint NCI's EDRN and NIST Workshop on Standards, Methods, Assays, Reagents and Tools.

The workshop report, entitled Towards Clinical Application of Methylated DNA Sequences as Cancer Biomarkers: A Joint National Cancer Institute's Early Detection Research Network and National Institute of Standards and Technology Workshop, presents a summary of the main issues, current challenges, outcomes, and recommendations toward application of methylated DNA sequences as cancer biomarkers.

Phosphoinositide-mediated adaptor recruitment controls Toll-like receptor signaling.

Toll-like receptors (TLRs) play a critical role in the immune system as sensors of microbial infection. Signaling downstream from TLRs is initiated by the recruitment of adaptor proteins, including MyD88 and TIRAP. These adaptors play essential roles in TLR signaling, but the mechanism of their function is currently unknown.

Young burned children: the course of acute stress and physiological and behavioral responses.

Objective: Symptoms of posttraumatic stress disorder (PTSD) are a focus of much research with older children, but little research has been conducted with young children, who account for about 40% of all pediatric burn injuries. This is a longitudinal study of 72 acutely burned children (12-48 months old) that assessed the course of acute posttraumatic symptoms and physiological reactivity.

Method: Parents were interviewed shortly after their child was admitted to the hospital and 1 month after discharge.

Trauma severity influences acute stress in young burned children.

The purpose of this study was to assess the role of trauma severity on subsequent symptoms of posttraumatic stress disorder (PTSD) and physiological reactivity in a total of 70 children, ranging from 12 to 48 months of age, who were acutely burned. Parents were interviewed shortly after the child was admitted to the hospital. PTSD symptoms were measured using the Posttraumatic Stress Disorder Semi-Structured Interview and Observational Record for Infants and Young Children and the Diagnostic Interview for Children and Adolescents.

Infant temperament and anxious symptoms in school age children.

A group of 164 children from different infant temperament categories were seen at 7 years of age for a laboratory battery that included behavioral and physiological measurements. The major results indicated that children who had been classified as high reactive infants at 4 months of age, compared with infants classified as low reactive, (a) were more vulnerable to the development of anxious symptoms at age 7 years, (b) were more subdued in their interactions with a female examiner, (c) made fewer errors on a task requiring inhibition of a reflex, and (d) were more reflective. Further, the high reactives who developed anxious symptoms differed from the high reactives without anxious symptoms with respect to fearful behavior in the second year and, at age 7 years, higher diastolic blood pressure, a narrower facial skeleton, and greater magnitude of cooling of the temperature of the fingertips to cognitive challenge.

Analysis of Rab1 recruitment to vacuoles containing Legionella pneumophila.

Legionella pneumophila is an intracellular bacterial pathogen that utilizes a type IV secretion system to subvert the function of the Rab1 GTPase. Bacterial proteins translocated into host cells mediate the accumulation of the Rab1 protein on vacuoles containing Legionella pneumophila. Assays used to investigate recruitment of Rab1 by L.

Association of behavioral inhibition with hair pigmentation in a European sample.

Behavioral inhibition, a temperamental trait signalling a predisposition to childhood and adolescent anxiety disorders, is slightly more frequent in America among Caucasian children having blue irises. This paper examines a community sample of 101 German toddlers assessed for behavioral inhibition in a standardized laboratory procedure. Hair pigmentation was found to be significantly associated with behavioral inhibition in the sense that blond children exhibited higher fear scores.

Mitochondria as a target for early detection and diagnosis of cancer.

Mitochondrial dysfunction and mutations in mitochondrial DNA (mtDNA) have been frequently reported in cancer, neurodegenerative diseases, diabetes, and aging syndromes. The mitochondrion genome (16.5 Kb) codes only for a small fraction (estimated to be 1%) of the proteins housed within this organelle.

Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA.

Toll-like receptors (TLRs) sense infection by detecting molecular structures of microbial origin. TLR3, TLR7 and TLR9 recognize nucleic acids and are localized to intracellular compartments where they normally respond to viral nucleic acids. The purpose for this intracellular localization, however, is not clear.

Human morality and temperament.

This chapter has tried to make two points. First, the concept of morality refers to a developmental cascade of phenomena whose essential features are (a) inhibition of punished acts; (b) a representation of prohibited actions; (c) the emotions of uncertainty, empathy, shame, and guilt; (d) the semantic concepts of good and bad; (e) accepting the moral obligations of social categories; and (f) the concepts of fairness and the ideal. The inhibition of prohibited actions and the cognitive representation of prohibited behaviors, as well as the affect states that follow violations, appear by the end of the second year of life.

A time for specificity.

McGrath's (2005/this issue) article, "Conceptual Complexity and Construct Validity," is a happy sign that the serious reform necessary for theoretical progress in the study of human personality and psychopathology may be entering a formative phase.

The human Y chromosome suppresses the tumorigenicity of PC-3, a human prostate cancer cell line, in athymic nude mice.

The loss of the Y chromosome is a frequent numerical chromosomal abnormality observed in human prostate cancer. In cancer, loss of specific genetic material frequently accompanies simultaneous inactivation of tumor suppressor genes. It is not known whether the Y chromosome harbors such genes.

The corticotropin-releasing hormone gene and behavioral inhibition in children at risk for panic disorder.

Background: Behavioral inhibition to the unfamiliar (BI) is a heritable temperamental phenotype involving the tendency to display fearful, avoidant, or shy behavior in novel situations. BI is a familial and developmental risk factor for panic and phobic anxiety disorders. We previously observed an association between BI and a microsatellite marker linked to the corticotropin releasing hormone (CRH) gene in children at risk for panic disorder.

Association of selected phenotypic markers of lymphocyte activation and differentiation with perinatal human immunodeficiency virus transmission and infant infection.

This study of a subset of women and infants participating in National Institutes of Health Pediatric AIDS Clinical Trials Group protocol 185 evaluated lymphocyte phenotypic markers of immune activation and differentiation to determine their association with the likelihood of human immunodeficiency virus (HIV) transmission from the women to their infants and the potential for early identification and/or prognosis of infection in the infants. Lymphocytes from 215 human immunodeficiency virus type 1 (HIV)-infected women and 192 of their infants were analyzed by flow cytometry with an extended three-color panel of monoclonal antibodies. Women who did not transmit to their infants tended to have higher CD4+ T cells.

Serum neopterin, an immune activation marker, independently predicts disease progression in advanced HIV-1 infection.

Background: CD4+ T lymphocyte (CD4) counts and plasma human immunodeficiency virus (HIV) type 1 RNA concentrations predict clinical outcome in HIV-1 infection. Our objective was to assess the independent prognostic value for disease progression of soluble markers of immune system activation.

Methods: This retrospective marker-validation study utilized previously obtained clinical and laboratory data, including CD4+ cell counts, and made use of stored frozen serum samples to assay for levels of beta2-microglobulin, neopterin, endogenous interferon, triglycerides, interleukin-6, soluble tumor necrosis factor- alpha receptor II, and HIV-1 RNA, and to determine HIV genotypic reverse-transcriptase inhibitor resistance.

Evaluation of serum protein profiling by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry for the detection of prostate cancer: I. Assessment of platform reproducibility.

Background: Protein expression profiling for differences indicative of early cancer has promise for improving diagnostics. This report describes the first stage of a National Cancer Institute/Early Detection Research Network-sponsored multiinstitutional evaluation and validation of this approach for detection of prostate cancer.

Methods: Two sequential experimental phases were conducted to establish interlaboratory calibration and standardization of the surface-enhanced laser desorption (SELDI) instrumental and assay platform output.

A C-terminal translocation signal required for Dot/Icm-dependent delivery of the Legionella RalF protein to host cells.

The Legionella pneumophila Dot/Icm system is a type IV secretion apparatus that transfers bacterial proteins into eukaryotic host cells. The RalF protein is a substrate engaged and translocated into host cells by the Dot/Icm system. In this study, the mechanism of Dot/Icm-mediated translocation of RalF has been investigated.

Human amygdala responsivity to masked fearful eye whites.

The amygdala was more responsive to fearful (larger) eye whites than to happy (smaller) eye whites presented in a masking paradigm that mitigated subjects' awareness of their presence and aberrant nature. These data demonstrate that the amygdala is responsive to elements of.

The early detection research network surface-enhanced laser desorption and ionization prostate cancer detection study: A study in biomarker validation in genitourinary oncology.

Prostate-specific antigen (PSA) screening has led to a dramatic increase in prostate cancer detection with a concurrent stage migration. Although the test has revolutionized prostate cancer detection by identifying disease that is potentially curable in the majority of men, only 25% of men receiving test results of PSA > 4 ng/ml will have prostate cancer and many men receiving a normal PSA will have disease, including high-grade disease. There is a need for improved biomarkers for detecting prostate cancer.

Serum protein expression profiling for cancer detection: validation of a SELDI-based approach for prostate cancer.

Multiple studies have reported that analysis of serum and other bodily fluids using surface enhanced laser desorption/ionization time of flight mass spectroscopy (SELDI-TOF-MS) can identify a "fingerprint" or "signature" of spectral peaks that can separate patients with a specific disease from normal control patients. Ultimately, classification by SELDI-TOF-MS relies on spectral differences in position and amplitude of resolved peaks. Since the reproducibility of quantitation, resolution and mass accuracy of the SELDI-TOF-MS, or any high throughput mass spectrometric technique, has never been determined this method has come under some skepticism as to its clinical usefulness.

Immunophenotypic markers and antiretroviral therapy (IMART): T cell activation and maturation help predict treatment response.

To determine whether markers of T cell activation and maturation are independently predictive of the response to potent antiretroviral therapy, the Immunophenotypic Markers and Antiretroviral Therapy study applied a novel data-sharing strategy across 5 Adult AIDS Clinical Trial Group trials that counted naive and activated CD4(+) and CD8(+) T cells in 324 subjects. Regression models--adjustment for baseline CD4 cell count, human immunodeficiency virus (HIV) RNA, and study--revealed that high pretreatment CD8(+) T cell activation predicted virologic failure (P=.046).

Legionella subvert the functions of Rab1 and Sec22b to create a replicative organelle.

Legionella pneumophila is a bacterial pathogen that infects eukaryotic host cells and replicates inside a specialized organelle that is morphologically similar to the endoplasmic reticulum (ER). To better understand the molecular mechanisms governing transport of the Legionella-containing vacuole (LCV), we have identified host proteins that participate in the conversion of the LCV into a replicative organelle. Our data show that Rab1 is recruited to the LCV within minutes of uptake.