Neuropsychological functions,sleep, and mental health in adults with Klinefelter syndrome

A few studies have examined neuropsychological functions, sleep, and mental health combined in Klinefelter syndrome (KS; 47,XXY). We investigated neuropsychological functions with standard tests, sleep with actigraphy, and self‐reported mental health in 30 men with KS (Mean age = 36.7 years) compared to 21 controls (Mean age = 36.8 years). Men with KS scored significantly lower on mental speed, attention span, working memory, inhibition, and set‐shifting tests, as well as overall IQ (mean effect size difference Cohen's d = 0.79). Men with KS had significantly longer night wakes, with no differences in other sleep variables (mean d = 0.34). Men with KS reported poorer mental health than controls (mean d = 1.16). Regression analyses showed neuropsychological functions explained variance in some sleep domains for men with KS but not for controls. Neuropsychological functions explained variance in some mental health domains for controls. For men with KS, however, verbal IQ was the only significant predictor of mental health. Altogether, men with KS display problems in neuropsychological functions and mental health but do not appear different from controls on most sleep parameters. Our findings indicate that relations between neuropsychological functions, sleep, and mental health differ between men with KS and controls.     

Presymptomatic diagnosis of SMA III by genotype analysis

Linkage analysis and prenatal prediction in families segregating autosomal recessive spinal muscular atrophy (SMA) has become feasible since the assignment of the locus responsible for type I-III SMA to region 5q12-q13.3. We have performed a segregation study of SMA in Italian families using molecular probes and highly informative PCR-based polymorphic markers. In one family, a 7-year-old boy affected with type III SMA and an 8-year-old apparently healthy brother had identical haplotypes. These findings prompted us to reexamine the apparently unaffected child. His neurological exam was normal. However, the electromyography (EMG) showed a pattern consistent with chronic SMA. To our knowledge this is the first example of presymptomatic diagnosis of SMA based on genotype analysis. © 1993 Wiley-Liss, Inc.     

Lactoferrin gene expression is estrogen responsive in human and rhesus monkey endometrium.

We have previously shown that the estrogen responsiveness of the human lactoferrin gene in a transient transfection system is mediated through an imperfect estrogen response element (ERE) and a steroidogenic factor 1 binding element (SFRE) 26 bp upstream from ERE. Reporter constructs containing SFRE and ERE respond to estrogen stimulation in a dose-dependent manner, whereas mutations at either one of the response elements severely impaired the estrogen responsiveness. In this study, we demonstrated that estrogen receptor (ERalpha) binds to the human lactoferrin gene ERE and forms two complexes in an electrophoresis mobility shift assay (EMSA). These complexes could be supershifted by an antibody to ERalpha. We also showed that in normal cycling women, lactoferrin gene expression in the endometrium increases during the proliferative phase and diminishes during the luteal phase. This in-vivo study thus supported the finding from transient transfection experiments that the human lactoferrin gene expression is elevated in an environment with a high level of estrogen. The estrogen effect on lactoferrin gene expression in the rhesus monkey endometrium was studied by Western blotting and immunohistochemistry. The immunohistochemistry results showed that immunoreactive lactoferrin protein was not detectable in the untreated ovariectomized monkey endometrium, was elevated by estrogen treatment, and was suppressed by sequential, combined estrogen plus progesterone treatment. In conclusion, this study has shown that lactoferrin gene expression is responsive to estrogen in primate endometrium.     

Behavioral Upset in Medical Patients-Revised: Evaluation of a Parent Report Measure of Distress for Pediatric Populations

Examined the utility of a new parent-report measure designedspecifically for pediatric inpatients, the Behavioral Upsetin Medical Patients-Revised (BUMP-R). The BUMP-R was administeredto 151 mothers of hospitalized children ages 4–12 yearsthe day following the child's hospital admission. The BUMP-Rdemonstrated good internal consistency and a factor analysisrevealed four factors identified as negativity/agitation, amiability,dysphoria, and noncom-pliance. Children exhibiting behavioraldistress at home were more likely to experience adjustment problemsupon hospitalization. Demographic and illness-related variableswere not substantial risk factors for hospital adjustment difficulties.     

On the various manifestations of spontaneous autoimmune diabetes in rodent models

Autoimmune (type 1) diabetes mellitus in mouse, rat, and humans shares several features, including T lymphocyte infiltration into pancreatic islets and a dependence on permissive class II major histocompatibility complex (MHC) alleles. We report here on an experimental model involving mice that express influenza hemagglutinin (HA) under the control of the insulin promoter and, at the same time, a transgenic class II MHC-restricted T cell receptor (TcR) specific for an HA peptide. These mice spontaneously develop islet infiltrates resembling those found in NOD mice and most animals become diabetic within 8 weeks of age. Because of the availability of a clonotypic TcR antibody, we can be confident that the Ins-HA transgene does not induce any measurable alterations in the vast majority of T cells with the transgenic TcR in primary and secondary lymphoid organs. Continuous export of large numbers of HA-specific lymphocytes from the thymus was not required for the manifestation of the disease since mice thymectomized at 3 days after birth still developed the disease albeit with smaller infiltrates.     

Peptide-based approaches to treat asthma, arthritis, other autoimmune diseases and pathologies of the central nervous system

In this review we focus on peptide- and peptidomimetic-based approaches that target autoimmune diseases and some pathologies of the central nervous system. Special attention is given to asthma, allergic rhinitis, osteoarthritis, and Alzheimer's disease, but other related pathologies are also reviewed, although to a lesser degree. Among others, drugs like Diacerhein and its active form Rhein, Pralnacasan, Anakinra (Kineret), Omalizumab, an antibody "BION-1", directed against the common beta-chain of cytokine receptors, are described below as well as attempts to target beta-amyloid peptide aggregation. Parts of the review are also dedicated to targeting of pathologic conditions in the brain and in other tissues with peptides as well as methods to deliver larger molecules through the "blood--brain barrier" by exploring receptor-mediated transport, or elsewhere in the body by using peptides as carriers through cellular membranes. In addition to highlighting current developments in the field, we also propose, for future drug targets, the components of the inflammasome protein complex, which is believed to initiate the activation of caspase- 1 dependent signaling events, as well as other pathways that signal inflammation. Thus we discuss the possibility of targeting inflammasome components for negative or positive modulation of an inflammatory response.     

Regulation of ST2L expression on T helper (Th) type 2 cells

T1/ST2L, an IL-1 receptor homologue, is selectively expressed on murine Th2 cells and specific anti-ST2L antibodies can profoundly modulate the Th1/Th2 balance in vivo. Naive CD4+ T cells do not express ST2L but do so on activation with specific antigen in the presence of IL-4 or when stimulated with low doses of antigen in the absence of exogenously added IL-4. Similarly enhanced ST2L expression occurred after stimulation of Th2 cells with antigen or the mitogen ConA in the presence of APC. Restimulation of Th2 cells in the presence of IFN-gamma led to a decreased expression of ST2L to below basal levels. Conversely, Th2 cells cultured with IL-4 led to increased ST2L expression. The reduced expression of ST2L in response to high doses of antigen is also reversed by the neutralization of IFN-gamma. Using an ST2L promoter/luciferase reporter gene construct, we show that the distal but not proximal ST2L promoter is responsible for specific gene expression in Th2 cells. IL-4 enhances, whereas IFN-gamma suppresses ST2L expression via direct modulation of the distal promoter of the ST2L gene. These data provide a mechanistic explanation for the selective expression of ST2L on Th2 cells.     

An adjective list for assessing emotional expressivity in psychotherapy research

Background: Several forms of psychotherapy aim at improving their patients' emotional expressivity, which is considered to contribute to mental health. Studies on the success of such attempts are virtually absent. Aim: To develop a measure for assessing changes of emotional expressivity in the course of psychotherapy. Method: In study 1 (N = 321), we generated a pool of German adjectives referring to emotional expressivity and reduced the number of those adjectives by means of factor‐analysis. In study 2 (N = 103), we determined how emotional expressivity is related to the Big Five personality factors. Results: An expressivity scale of 12 items with highly satisfactory psychometric properties was construed. Emotional expressivity is substantially related to Extraversion and moderately related to Agreeableness and Openness. Conclusion: The scale is ideally suited for repeated assessments in the course of psychotherapy in multi‐agent (e.g., inpatient) settings. Copyright © 2007 John Wiley & Sons, Ltd.