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The school counselor is a logical choice for leadership in making "inclusion" a successful experience for those involved. Counselors' active involvement in networking among students, educational professionals, families, community, and social agencies should work toward the realization of many of the goals of inclusive education and inclusive society. (EMK)

Overactivity of the dopaminergic system in the brain is considered to be a contributing factor to the development and symptomatology of schizophrenia. Therefore, the GABAergic control of dopamine functions was assessed by disrupting the gene encoding the [alpha]3 subunit of the GAB[A.sub.A] receptor. [alpha]3 knockout ([alpha]3KO) mice exhibited neither an obvious developmental defect nor apparent morphological brain abnormalities, and there was no evidence for compensatory up-regulation of other major GAB[A.sub.A]-receptor subunits. Anxiety-related behavior in the elevated-plus-maze test was undisturbed, and the anxiolytic-like effect of diazepam, which is mediated by [alpha]2-containing GAB[A.sub.A] receptors, was preserved. As a result of the loss of [alpha]3 GAB[A.sub.A] receptors, the GABA-induced whole-cell current recorded from midbrain dopamine neurons was significantly reduced. Spontaneous locomotor activity was slightly elevated in [alpha]3KO mice. Most notably, prepulse inhibition of the acoustic startle reflex was markedly attenuated in the [alpha]3KO mice, pointing to a deficit in sensorimotor information processing. This deficit was completely normalized by treatment with the antipsychotic D2-receptor antagonist haloperidol. The amphetamine-induced hyperlocomotion was not altered in [alpha]3KO mice compared with WT mice. These results suggest that the absence of [alpha]3-subunit-containing GAB[A.sub.A] receptors induces a hyperdopaminergic phenotype, including a severe deficit in sensorimotor gating, a common feature among psychiatric conditions, including schizophrenia. Hence, agonists acting at [alpha]3-containing GAB[A.sub.A] receptors may constitute an avenue for an effective treatment of sensorimotor-gating deficits in various psychiatric conditions. haloperidol | sensorimotor gating

Studer, R. K., E. Levicoff, H. Georgescu, L. Miller, D. Jaffurs, and C. H. Evans. Nitric oxide inhibits chondrocyte response to IGF-I: inhibition of IGF-IR[Beta] tyrosine phosphorylation. Am J Physiol Cell Physiol 279: C961-C969, 2000.--Chondrocytes in arthritic cartilage respond poorly to insulin-like growth factor I (IGF-I). Studies with inducible nitric oxide synthase (iNOS) knockout mice suggest that NO is responsible for part of the cartilage insensitivity to IGF-I. These studies characterize the relationship between NO and chondrocyte responses to IGF-I in vitro, and define a mechanism by which NO decreases IGF-I stimulation of chondrocyte proteoglycan synthesis. Lapine cartilage slices, chondrocytes, and cartilage from osteoarthritic (OA) human knees were exposed to NO from the donors S-nitroso-N-acetylpenicillamine (SNAP) or (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl) amino]diazen-1-ium-1,2-diolate] (DETA NONOate), by transduction with adenoviral transfer of iNOS (Ad-iNOS), or by activation with interleukin-1 (IL-1). NO synthesis was estimated from medium nitrite, and proteoglycan synthesis was measured as incorporation of [sup.35][SO.sub.4]. IGF-I receptor phosphorylation was evaluated with Western analysis. SNAP, DETA NONOate, endogenously synthesized NO in Ad-iNOS-transduced cells, or IL-1 activation decreased IGF-I-stimulated proteoglycan synthesis in cartilage and monolayer cultures of chondrocytes. OA cartilage responded poorly to IGF-I; however, the response to IGF-I was restored by culture with [N.sup.G]-monomethyl-L-arginine (L-NMA). IGF-I receptor phosphotyrosine was diminished in chondrocytes exposed to NO. These studies show that NO is responsible for part of arthritic cartilage/chondrocyte insensitivity to anabolic actions of IGF-I; inhibition of receptor autophosphorylation is potentially responsible for this effect. chondrocytes; arthritis; signal transduction; matrix proteoglycan synthesis; cartilage; insulin-like growth factor I; insulin-like growth factor I receptor

Objective Low back pain is frequently treated with nonsteroidal anti-inflammatory drugs (NSAIDs), but little is known about intervertebral disc metabolism of the prostaglandins that are diminished by these drugs. Hence, this study aimed at delineating prostaglandin actions in cytokine activated disc cells by comparing the response of nucleus pulposus (NP) cells to the pro-inflammatory cytokine interleukin (IL)-1β with and without cyclooxygenase 2 (COX-2) inhibition. Methods NP cells cultured in alginate beads were activated with IL-1β ± the COX-2 inhibitor Sc-58125. Media harvested from cultured cells were analyzed for prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2α), IL-6, and matrix metalloproteinase (MMP)-3 by enzyme-linked immunosorbent assay and nitric oxide by Griess Reaction. Gene expression along with proteoglycan, collagen, and total protein synthesis were also measured. Results IL-1β increased culture media PGE2 and PGF2α, but decreased proteoglycan and collagen syntheses as well as mRNA expression of the matrix genes aggrecan, versican, collagen I, and collagen II. COX-2 inhibition partially rescued proteoglycan and collagen syntheses and collagen I mRNA, but decreased collagen II mRNA IL-1β activated NP cells. COX-2 inhibition initially enhanced and subsequently reduced IL-1β induced inducible nitric oxide synthase, without altering medium nitrite. IL-1β induction of MMP-3 mRNA was increased by COX-2 inhibition at 24 and 48 hours. Conclusion COX-2 inhibition alters the response of NP cells to IL-1β, suggesting IL-1β action on disc cells is mediated at least in part through COX-2 and its prostaglandins. COX-2 inhibition produces minimal effects on several key catabolic mediators, with the exception of MMP-3. Blocking COX-2 might be beneficial for maintaining disc matrix since it provides an overall rescue of IL-1 induced loss of matrix protein synthesis.

Background: Collembola (springtails) represent a soil-living lineage of hexapods in between insects and crustaceans. Consequently, their genomes may hold key information on the early processes leading to evolution of Hexapoda from a crustacean ancestor. Method: We assembled and annotated transcriptomes of the Collembola Folsomia candida and Orchesella cincta, and performed comparative analysis with protein-coding gene sequences of three crustaceans and three insects to identify adaptive signatures associated with the evolution of hexapods within the pancrustacean clade. Results: Assembly of the springtail transcriptomes resulted in 37,730 transcripts with predicted open reading frames for F. candida and 32,154 for O. cincta, of which 34.2% were functionally annotated for F. candida and 38.4% for O. cincta. Subsequently, we predicted orthologous clusters among eight species and applied the branch-site test to detect episodic positive selection in the Hexapoda and Collembola lineages. A subset of 250 genes showed significant positive selection along the Hexapoda branch and 57 in the Collembola lineage. Gene Ontology categories enriched in these genes include metabolism, stress response (i.e. DNA repair, immune response), ion transport, ATP metabolism, regulation and development-related processes (i.e. eye development, neurological development). Conclusions: We suggest that the identified gene families represent processes that have played a key role in the divergence of hexapods within the pancrustacean clade that eventually evolved into the most species-rich group of all animals, the hexapods. Furthermore, some adaptive signatures in collembolans may provide valuable clues to understand evolution of hexapods on land. [ABSTRACT FROM AUTHOR]

Ultrasound can be valuable in the assessment of salivary gland disease. This examination is simple, non-invasive and cost-effective. Few cases require the need for additional imaging modalities. The use of ultrasound can confirm a diagnosis that has been suggested by case history and findings. Evidence of a mass is an indication for fine-needle aspiration. This does not eliminate the need for histological follow-up. [ABSTRACT FROM AUTHOR]

Ultrasound can be valuable in the assessment of salivary gland disease. This examination is simple, non-invasive and cost-effective. Few cases require the need for additional imaging modalities. The use of ultrasound can confirm a diagnosis that has been suggested by case history and findings. Evidence of a mass is an indication for fine-needle aspiration. This does not eliminate the need for histological follow-up. [ABSTRACT FROM AUTHOR]

Overactivity of the dopaminergic system in the brain is considered to be a contributing factor to the development and symptomatology of schizophrenia. Therefore, the GABAergic control of dopamine functions was assessed by disrupting the gene encoding the α3 subunit of the GABAA receptor. α3 knockout (α3KO) mice exhibited neither an obvious developmental defect nor apparent morphological brain abnormalities, and there was no evidence for compensatory up-regulation of other major GABAA-receptor subunits. Anxiety-related behavior in the elevated-plus-maze test was undisturbed, and the anxiolytic-like effect of diazepam, which is mediated by α2-containing GABAA receptors, was preserved. As a result of the loss of α3 GABAA receptors, the GABA-induced whole-cell current recorded from midbrain dopamine neurons was significantly reduced. Spontaneous locomotor activity was slightly elevated in α3KO mice. Most notably, prepulse inhibition of the acoustic startle reflex was markedly attenuated in the α3KO mice, pointing to a deficit in sensorimotor information processing. This deficit was completely normalized by treatment with the antipsychotic D2-receptor antagonist haloperidol. The amphetamine-induced hyperlocomotion was not altered in α3KO mice compared with WT mice. These results suggest that the absence of α3- subunit-containing GABAA receptors induces a hyperdopaminergic phenotype, including a severe deficit in sensorimotor gating, a common feature among psychiatric conditions, including schizophrenia. Hence, agonists acting at α3-containing GABAA receptors may constitute an avenue for an effective treatment of sensori- motor-gating deficits in various psychiatric conditions. [ABSTRACT FROM AUTHOR]

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The diastolic and systolic dysfunction in the failing heart appear to be related to the altered Ca2+ handling of the cardiac myocyte. Disturbed Ca2+ handling might also affect influx and efflux of other ions, including Na+. In this context, the cardiac sarcolemmal Na+/Ca2+ exchanger represents an important exchange mechanism of Ca2+ versus Na+ transport across the sarcolemma. Expression and function of cardiac Na+/Ca2+ exchanger is highest in newborn rats and declines gradually in postnatal development. In pressure overload-induced hypertrophy, expression of cardiac Na+/Ca2+ exchanger is increased and translated into increased Na+/Ca2+ exchanger activity similar to the early phase of postnatal development in the rat. This suggests a common underlying mechanism in the control of Na+/ Ca2+ exchanger expression in the immature and the hypertrophied myocardium. Similar to experimental-induced hypertrophy, mRNA, protein and activity of Na+/Ca2+ exchanger is increased in the failing human heart suggesting an increase in the number of functional exchanger molecules rather than an enhanced exchange rate by preexisting exchanger molecules. The potential functional implications of an increased cardiac Na+/Ca2+ exchanger activity in human heart failure may be limitation of diastolic intracellular Ca2+ overload. However, this may increase the arrhythmogenic potential of the failing heart, since additional Na+ influx via Na+/Ca2+ exchanger may affect the membrane potential. [ABSTRACT FROM AUTHOR]

The effects of metabolic and respiratory acidosis and alkalosis on cellular calcium metabolism were studied in rat kidney cells dispersed with collagenase. In both types of acidosis, the intracellular pH, total cell calcium, and the cell relative radioactivity after 60 min of labeling are significantly depressed. Kinetic analysis of 45-ca desaturation curves shows that acidosis decreases all three cellular calcium pools and depresses calcium fluxes between the superficial and cytosolic pools and between the cytosolic and mitochondrial pools. In alkalosis the intracellular pH, the total cell calcium, and the cell relative radioactivity are significantly increased. Kinetic studies show that in alkalosis, only the mitochondrial pool is consistently increased. Calcium exchange between the mitochondrial and cytosolic pool is increased in metabolic alkalosis only. These results suggest that hydrogen ion is an important modulator of calcium metabolism, and that the intracellular pH rather than extracellular pH is the critical factor in determining the calcium status of cells during altered acid-base conditions. [ABSTRACT FROM AUTHOR]