Language and executive functioning in young adults with Down syndrome.

BACKGROUND: This study examined the association between executive functioning and language in young adults with Down syndrome (DS). METHOD: Nineteen young adults with DS (aged 19-24 years) completed standardised measures of overall cognition, vocabulary, verbal fluency and executive function skills. RESULTS: Friedman's analysis of variance (χ2 (3) = 28.15, P < .001) and post hoc comparisons indicated that, on average, participants had a significantly lower overall non-verbal than verbal cognitive age equivalent and lower expressive than receptive vocabulary skills. Using Spearman correlations, performance on a verbal measure of cognition inhibition was significantly negatively related to receptive vocabulary (ρ = -.529, adjusted P = .036) and verbal fluency (ρ = -.608, adjusted P = .022). Attention was significantly positively correlated with receptive (ρ = .698, adjusted-p = .005) and expressive (ρ = .542, adjusted P = .027) vocabulary. Verbal working memory was significantly positively associated with receptive vocabulary (ρ = .585, adjusted P = .022) and verbal fluency (ρ = .737, adjusted P = .003). Finally, visuospatial working memory was significantly associated with receptive vocabulary (ρ = .562, adjusted P = .027). CONCLUSIONS: Verbal and non-verbal measures of executive functioning skills had important associations with language ability in young adults with DS. Future translational research is needed to investigate causal pathways underlying these relationships. Research should explore if interventions aimed at increasing executive functioning skills (e.g. attention, inhibition and working memory) have the potential to lead to increases in language for young adults with DS.

A Study of Vitamin D among Patients Presenting in the Psychiatric OPD of Manipal Teaching Hospital, Pokhara.

Background There have been growing interests in the association between vitamin D and depression in recent years. Objective The objective of this study was to find the prevalence of low vitamin D level in the patients suffering from depressive episodes. The next objective was to determine whether there are any statistically significant differences between the mean vitamin D levels of different sociodemographic variables and also to find the sociodemographic variables predicting the vitamin D level. Method The patients diagnosed as depressive episodes were selected from the out-patient unit of Department of Psychiatry of Manipal Teaching Hospital, Pokhara. The proforma was used to collect the sociodemographic profile of the patient. The diagnosis of depressive episode was made according to the International Classification of Disease-10 Classification of Mental and Behavioural Disorders: Diagnostic Criteria for Research. The serum vitamin D level of less than 30 ng/ml was considered as low level in this study. Result The prevalence of low vitamin level was found in 81.8%. The mean difference of vitamin D level was statistically significant in gender and marital status of the patients. The low mean vitamin level was found in the socio-demographic variables like in age above 60 years, Newar caste, female gender, separated from the spouse patients and in the patients living in the urban area as compared to other group of patients. The gender of the patients predicted vitamin D level in the depressed patients. Conclusion There is high prevalence of low vitamin D level in the depressed patients. The correction of low vitamin D level would be helpful in the holistic management of patient with depressive episodes.

The implication of neuroactive steroids in Tourette's syndrome pathogenesis: A role for 5α-reductase?

Tourette's syndrome (TS) is a neurodevelopmental disorder characterised by recurring motor and phonic tics. The pathogenesis of TS is considered to reflect dysregulations in the signalling of dopamine (DA) and other neurotransmitters, which lead to excitation/inhibition imbalances in cortico-striato-thalamocortical circuits. The causes of these deficits may reflect complex gene × environment × sex (G × E × S) interactions; indeed, the disorder is markedly predominant in males, with a male-to-female prevalence ratio of approximately 4 : 1. Converging lines of evidence point to neuroactive steroids as being likely molecular candidates to account for G × E × S interactions in TS. Building on these premises, our group has begun examining the possibility that alterations in the steroid biosynthetic process may be directly implicated in TS pathophysiology; in particular, our research has focused on 5α-reductase (5αR), the enzyme catalysing the key rate-limiting step in the synthesis of pregnane and androstane neurosteroids. In clinical and preclinical studies, we found that 5αR inhibitors exerted marked anti-DAergic and tic-suppressing properties, suggesting a central role for this enzyme in TS pathogenesis. Based on these data, we hypothesise that enhancements in 5αR activity in early developmental stages may lead to an inappropriate activation of the 'backdoor' pathway for androgen synthesis from adrenarche until the end of puberty. We predict that the ensuing imbalances in steroid homeostasis may impair the signalling of DA and other neurotransmitters, ultimately resulting in the facilitation of tics and other behavioural abnormalities in TS.

Induction of hyporesponsiveness and impaired T lymphocyte activation by the CD31 receptor:ligand pathway in T cells.

CD31 is a member of the Ig superfamily expressed on various cell types of the vasculature, including a certain subpopulation of T lymphocytes. Previous reports suggest that interaction of CD31 with its heterophilic ligand on T cells (T cell CD31 ligand) plays a regulatory role in T lymphocyte activation. Here we demonstrate that a soluble rCD31-receptorglobulin (CD31Rg) specifically down-regulated the proliferation of human peripheral blood CD31(-) T lymphocytes stimulated via CD3 and CD28 mAbs. Notably, engagement of the T cell CD31 ligand by CD31Rg during primary stimulation also induced a prolonged unresponsive state in T cells. Retroviral transduction of CD31 into CD31(-) Th clones resulted in a significant inhibition of their proliferative capacity. When cocultured with purified CD31(-) T lymphocytes, irradiated CD31-transduced Th clones counterregulated the CD3/CD28-mediated activation of these cells. Furthermore, primary stimulation in the presence of CD31-transduced Th clones induced a comparable state of hyporesponsiveness in the T cell responders as the soluble CD31Rg. Thus, by counterregulating the activation of cognate T lymphocytes, CD31-expressing T cells might contribute to the establishment and maintenance of peripheral tolerance.

Use of color and responses to computer-based surveys.

Mean answers by 217 students to an affective questionnaire, the Mach IV survey, did not vary with the use of different background and font colors when the survey was presented online in a computer lab. They indicated, however, that background color may be associated with rate and within-condition variability of response.

M6P/IGFII-receptor complexes urokinase receptor and plasminogen for activation of transforming growth factor-beta1.

Transforming growth factor-beta1 (TGF-beta1) is a critical cytokine for cell proliferation and differentiation. It is secreted by many cells in a latent pro-form (LTGF-beta1) from which biologically active TGF-beta1 is released by an in vivo mechanism that is not known. Here we show that the mannose-6-phosphate/insulin-like growth factor II-receptor (M6P/IGFII-R), which binds LTGF-beta1, complexes with urokinase (plasminogen activator)-receptor (uPA-R) on the surface of human monocytes and directly binds plasminogen (Plg). Plasmin generated from Plg in the complex mediates release of TGF-beta1 when M6P/IGFII-R is associated with uPA-R. Thus, this interaction of M6P/IGFII-R and uPA-R suggests a potential mechanism for the generation of TGF-beta1 by cells.

Acquisition of host cell-surface-derived molecules by HIV-1.

OBJECTIVE: To determine the acquisition of host cell-membrane-derived molecules by HIV-1 during the budding process, and to investigate whether the uptake of these molecules is cell-type-specific and selective. DESIGN: Virions, propagated by four different cell types were analysed for the presence of adhesion molecules, glycosylphosphatidylinositol (GPI)-anchored proteins and various cell-surface markers. The pattern was compared with the phenotype of the HIV-1-infected cell. METHODS: For phenotypic analysis of virions a two-step assay was used. In the first step, virus was captured with monoclonal antibodies (in some cases polyclonal sera) against different cell-membrane proteins. In a second step, the presence of virus was measured by determining the concentration of the virus-specific p24 core antigen. The expression of surface molecules on uninfected and HIV-1IIIB-infected cells was analysed by FACS. RESULTS: Depending on the cell type used for virus propagation, different cell-membrane molecules were found on the virus surface reflecting the corresponding cell type. The uptake of these molecules was selective to a certain degree. No CD4 and CD87 molecules were detectable on HIV-1, although both molecules were present on uninfected and HIV-1-infected cells. CR3 and CDw108 could not be seen on uninfected cells, but wre detectable on infected cells and virions. CONCLUSIONS: During the budding process HIV-1 acquires a variety of cell-type-specific cell-surface molecules. Certain cell-membrane molecules become upregulated during HIV-1-infection and are then found on virions, whereas other molecules remain on the cell surface and do not become incorporated.

Alpha L beta 2 integrin/LFA-1 binding to ICAM-1 induced by cytohesin-1, a cytoplasmic regulatory molecule.

The avidity of integrin adhesion receptors for extracellular ligands is subject to dynamic regulation by intracellular programs that have yet to be elucidated. We describe here a protein, cytohesin-1, which specifically interacts with the intracellular portion of the integrin beta 2 chain (CD18). The molecule shows homology to the yeast SEC7 gene product and bears a pleckstrin homology (PH) domain. Overexpression of either the full-length cytohesin-1 or the SEC7 domain induces beta 2 integrin-dependent binding of Jurkat cells to ICAM-1, whereas expression of the isolated cytohesin-1 PH domain inhibits T cell receptor-stimulated adhesion. Similar inhibition is not exhibited by PH domains taken from other proteins, showing that the interaction is specific and that individual PH domains are capable of discriminating between alternative targets.

A gene (hur) from Streptomyces aureofaciens, conferring resistance to hydroxyurea, is related to genes encoding streptomycin phosphotransferase.

A novel gene (hur) conferring resistance to hydroxyurea (HU) in Escherichia coli has been identified in a Streptomyces aureofaciens genomic library. The expression of hur in E. coli was under the control of the external plasmid tet promoter. Sequence analysis of a minimal fragment revealed an open reading frame (ORF) encoding a protein of 340 amino acids with an M(r) of 36,049 and an average hydropathy index of 1.13. The predicted protein product was similar to streptomycin phosphotransferases from Streptomyces glaucescens and Streptomyces griseus (52.4% and 50.8% identity, respectively), but it did not confer resistance to streptomycin or to any of the other aminoglycoside antibiotics tested. It is inferred that hur encodes a phosphotransferase that inactivates HU by phosphorylation of the hydroxy group in the hydroxylamine moiety.

Focal penicillin seizures--motor activity and cellular physiology and morphology.

Two types of intracellular activity have been found in neurons in the cortical penicillin seizure focus during an interictal spike; a prolonged depolarization (PDS) followed by hyperpolarization or predominantly hyperpolarization. In the present study of a penicillin focus we have correlated the penicillin focus location with motor behavior and the cellular physiology with cellular morphology and location. Penicillin injection at the same location in the anterior sigmoid gyrus invariably resulted in focal seizures involving the contralateral shoulder. From the locations of the myoclonus and the focus, the character of the movements and the route of seizure spread we conclude that the same pathways mediate movement produced by penicillin seizures or by electrically stimulating the same motor cortex. Intracellular recordings and dye-marking of cells in and around the seizure focus revealed that PDS neurons were located within a 3 mm radius from the site of penicillin injection. All PDS neurons either lacked well filled processes or had abnormal dendrites. Inhibited neurons were all pyramidal neurons with normal dendrites. The dendritic abnormalities observed could be important in the genesis of the PDS.

Cholecystokinin in hippocampal pathways.

The distribution of cholecystokininlike (CCK-L) immunoreactive cells and fibers in the rat hippocampal formation and its afferent and efferent connections was studied using the immunoperoxidase technique. In the hippocampal formation CCK-L immunoreactive perikarya were located in the polymorphic zone of the dentate hilus, all layers of Ammon's horn, the subiculum, the presubiculum, and the entorhinal cortex. Cholecystokininlike immunoreactive fibers extended from cell bodies or were located around the cell bodies in the entorhinal cortex, subiculum and stratum pyramidale of Ammon's horn, and among the granule cells and inner molecular layer of the dentate gyrus. The immunoreactive cells in the stratum oriens may be a type of basket cell, since processes from these cells extend into stratum pyramidale and collections of CCK-L immunoreactive fibers are seen around cell bodies in stratum pyramidale. Cholecystokininlike immunoreactive fibers were also observed in the alveus, ventral and lateral fimbria, and ventrolateral lateral septal nucleus. Some of these immunoreactive fibers, therefore, being to either an efferent or afferent hippocampal pathway(s) originating from CCK-L immunoreactive pyramidal cells in the hippocampal formation and/or from the hippocampal subcortical nuclei, the supramammillary nucleus, and the dorsomedial hypothalamic nucleus which contain CCK-L immunoreactive perikarya. The distribution of these immunoreactive fibers in the fimbria and lateral septal nucleus is most consistent with an anteriorly directed efferent hippocampal pathway.