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1.
Neuroscience ; 310: 12-26, 2015 Dec 03.
Article in English | MEDLINE | ID: mdl-26363150

ABSTRACT

Treatment of Parkinson's disease (PD) with dopamine replacement relieves symptoms of poverty of movement, but often causes drug-induced dyskinesias. Accumulating clinical and pre-clinical evidence suggests that the primary motor cortex (M1) is involved in the pathophysiology of PD and that modulating cortical activity may be a therapeutic target in PD and dyskinesia. However, surprisingly little is known about how M1 neurotransmitter tone or gene expression is altered in PD, dyskinesia or associated animal models. The present study utilized the rat unilateral 6-hydroxydopamine (6-OHDA) model of PD/dyskinesia to characterize structural and functional changes taking place in M1 monoamine innervation and gene expression. 6-OHDA caused dopamine pathology in M1, although the lesion was less severe than in the striatum. Rats with 6-OHDA lesions showed a PD motor impairment and developed dyskinesia when given L-DOPA or the D1 receptor agonist, SKF81297. M1 expression of two immediate-early genes (c-Fos and ARC) was strongly enhanced by either L-DOPA or SKF81297. At the same time, expression of genes specifically involved in glutamate and GABA signaling were either modestly affected or unchanged by lesion and/or treatment. We conclude that M1 neurotransmission and signal transduction in the rat 6-OHDA model of PD/dyskinesia mirror features of human PD, supporting the utility of the model to study M1 dysfunction in PD and the elucidation of novel pathophysiological mechanisms and therapeutic targets.


Subject(s)
AIDS-Related Complex/metabolism , Dyskinesia, Drug-Induced/pathology , Gene Expression/physiology , Motor Cortex/metabolism , Proto-Oncogene Proteins c-fos/metabolism , Synaptic Transmission/physiology , AIDS-Related Complex/genetics , Animals , Benzazepines/adverse effects , Disease Models, Animal , Dopamine Agents/adverse effects , Dyskinesia, Drug-Induced/etiology , Functional Laterality/drug effects , Gene Expression/drug effects , Levodopa/therapeutic use , Male , Medial Forebrain Bundle/injuries , Oxidopamine/toxicity , Parkinsonian Disorders/chemically induced , Parkinsonian Disorders/drug therapy , Proto-Oncogene Proteins c-fos/genetics , Rats , Rats, Sprague-Dawley , Severity of Illness Index , Synaptic Transmission/drug effects
2.
Nature ; 465(7300): 897-900, 2010 Jun 17.
Article in English | MEDLINE | ID: mdl-20559381

ABSTRACT

The Kuiper belt is a collection of small bodies (Kuiper belt objects, KBOs) that lie beyond the orbit of Neptune and which are believed to have formed contemporaneously with the planets. Their small size and great distance make them difficult to study. KBO 55636 (2002 TX(300)) is a member of the water-ice-rich Haumea KBO collisional family. The Haumea family are among the most highly reflective objects in the Solar System. Dynamical calculations indicate that the collision that created KBO 55636 occurred at least 1 Gyr ago. Here we report observations of a multi-chord stellar occultation by KBO 55636, which occurred on 9 October 2009 ut. We find that it has a mean radius of 143 +/- 5 km (assuming a circular solution). Allowing for possible elliptical shapes, we find a geometric albedo of in the V photometric band, which establishes that KBO 55636 is smaller than previously thought and that, like its parent body, it is highly reflective. The dynamical age implies either that KBO 55636 has an active resurfacing mechanism, or that fresh water-ice in the outer Solar System can persist for gigayear timescales.

3.
Neuroscience ; 156(1): 30-41, 2008 Sep 22.
Article in English | MEDLINE | ID: mdl-18687386

ABSTRACT

While the etiology of Parkinson's disease (PD) remains unknown, there is overwhelming evidence that neuroinflammation plays a critical role in the progressive loss of dopamine (DA) neurons. Because nearly all persons suffering from PD receive l-DOPA, it is surprising that inflammation has not been examined as a potential contributor to the abnormal involuntary movements (AIMs) that occur as a consequence of chronic l-DOPA treatment. As an initial test of this hypothesis, we examined the effects of exogenously administered corticosterone (CORT), an endogenous anti-inflammatory agent, on the expression and development of l-DOPA-induced dyskinesia (LID) in unilateral DA-depleted rats. To do this, male Sprague-Dawley rats received unilateral medial forebrain bundle 6-hydroxydopamine lesions. Three weeks later, l-DOPA primed rats received acute injections of CORT (0-3.75 mg/kg) prior to l-DOPA to assess the expression of LID. A second group of rats was used to examine the development of LID in l-DOPA naïve rats co-treated with CORT and l-DOPA for 2 weeks. AIMs and rotations were recorded. Exogenous CORT dose-dependently attenuated both the expression and development of AIMs without affecting rotations. Real-time reverse-transcription polymerase chain reaction of striatal tissue implicated a role for interleukin-1 (IL-1) beta in these effects as its expression was increased on the lesioned side in rats treated with l-DOPA (within the DA-depleted striatum) and attenuated with CORT. In the final experiment, interleukin-1 receptor antagonist (IL-1ra) was microinjected into the striatum of l-DOPA-primed rats to assess the impact of IL-1 signaling on LID. Intrastriatal IL-1ra reduced the expression of LID without affecting rotations. These findings indicate a novel role for neuroinflammation in the expression of LID, and may implicate the use of anti-inflammatory agents as a potential adjunctive therapy for the treatment of LID.


Subject(s)
Corticosterone/pharmacology , Dyskinesia, Drug-Induced/drug therapy , Encephalitis/drug therapy , Interleukin-1beta/immunology , Levodopa/adverse effects , Parkinsonian Disorders/drug therapy , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Corpus Striatum/drug effects , Corpus Striatum/immunology , Corpus Striatum/physiopathology , Corticosterone/therapeutic use , Disease Models, Animal , Dose-Response Relationship, Drug , Dyskinesia, Drug-Induced/immunology , Dyskinesia, Drug-Induced/physiopathology , Encephalitis/complications , Encephalitis/immunology , Interleukin 1 Receptor Antagonist Protein/pharmacology , Male , Medial Forebrain Bundle/drug effects , Medial Forebrain Bundle/physiopathology , Neural Pathways/drug effects , Neural Pathways/immunology , Neural Pathways/physiopathology , Oxidopamine , Parkinsonian Disorders/immunology , Parkinsonian Disorders/physiopathology , RNA, Messenger/analysis , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Substantia Nigra/drug effects , Substantia Nigra/immunology , Substantia Nigra/physiopathology , Sympatholytics , Up-Regulation/drug effects
4.
J Appl Psychol ; 83(1): 112-8, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9494443

ABSTRACT

The authors hypothesized that children's perceptions of their parents' job insecurity mediate the effects of parental job insecurity and layoffs on children's work beliefs and work attitudes. Male and female undergraduate students (N = 134; M age = 18.9 years), as well as their mothers (M age = 47.0 years) and fathers (M age = 49.1 years), participated voluntarily. With structural equation modeling as implemented by LISREL VIII, support for the proposed model was obtained, whereas no support was obtained for a competing model. Moreover, identification with fathers moderated the influence of perceived paternal job insecurity on children's humanistic work beliefs, but no comparable effect emerged for mothers.


Subject(s)
Attitude , Employment , Job Satisfaction , Parent-Child Relations , Parents/psychology , Adult , Female , Humans , Male
8.
J Am Acad Dermatol ; 15(1): 1-10, 1986 Jul.
Article in English | MEDLINE | ID: mdl-2941461

ABSTRACT

A general review is given of airborne-induced contact dermatoses, particularly of the irritant and allergenic types. Because the reports in the literature often omit the term airborne, 12 volumes of Contact Dermatitis (January 1975-July 1985) were screened, and the cases cited were classified in function of the anamnesis, lesion locations, causative irritants and allergens, and other factors. The present article also discusses differential diagnoses, in particular with regard to contact dermatitis of the face, ears, and neck. Finally, seven case reports of occupational and nonoccupational contact dermatitis problems caused by airborne agents are presented. In some of the cases the allergens have not been mentioned in published literature previously.


Subject(s)
Air Pollutants/adverse effects , Dermatitis, Contact/etiology , Adult , Aged , Captan/adverse effects , Cobalt/adverse effects , Dermatitis, Contact/diagnosis , Dermatitis, Contact/pathology , Dermatitis, Occupational/etiology , Detergents/adverse effects , Eczema/etiology , Erythema/etiology , Female , Humans , Male , Middle Aged , Perfume/adverse effects , Pyrithioxin/adverse effects , Quinolines/adverse effects , Thiram/adverse effects , Turpentine/adverse effects
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