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Sample records for juvenile neuronal ceroid

  1. Neurobehavioral Features and Natural History of Juvenile Neuronal Ceroid Lipofuscinosis (Batten Disease)

    PubMed Central

    Adams, Heather R; Mink, Jonathan W

    2014-01-01

    Juvenile neuronal ceroid lipofuscinosis is a childhood-onset neurodegenerative disease with prominent symptoms comprising a pediatric dementia syndrome: intellectual decline, mood and behavioral impairments, and loss of adaptive skills. We review the history of neurobehavioral features in juvenile neuronal ceroid lipofuscinosis and the work of the University of Rochester Batten Center to characterize the extent and progression of neurobehavioral symptoms over disease course, and discuss the relevance of neurobehavioral studies as an aid to understanding the clinical phenotype of juvenile Batten disease and potential targets for intervention. PMID:24014508

  2. Late onset juvenile neuronal ceroid-lipofuscinosis with granular osmiophilic deposits (GROD)

    SciTech Connect

    Hofman, I.L.; Taschner, P.E.M.

    1995-06-05

    The juvenile-onset subtype of the neuronal ceroid lipofuscinoses (JNCL) is well known and ultra-structurally characterized by fingerprints and/or curvilinear bodies in many cell types. Linkage studies indicated a most likely location for CLN3, the gene involved in JNCL, in the interval between loci D16S297 and D16S57, within close proximity of the loci D16S298 and D16S299. We present two sibs with a late onset progressive disease of mental deterioration, progressive macular degeneration, motor disturbances, and epilepsy. Histological symptoms of neuronal ceroid lipofuscinosis and ultrastructural granular osmiophilic deposits (GROD) in lymphocytes and neurons are found. Individual haplotypes at polymorphic marker loci on chromosome 16 were constructed to determine whether JNCL with GROD is linked to the CLN3 locus. 8 refs., 3 figs.

  3. Standardized assessment of seizures in patients with juvenile neuronal ceroid lipofuscinosis.

    PubMed

    Augustine, Erika F; Adams, Heather R; Beck, Christopher A; Vierhile, Amy; Kwon, Jennifer; Rothberg, Paul G; Marshall, Frederick; Block, Robert; Dolan, James; Mink, Jonathan W

    2015-04-01

    To evaluate seizure phenomenology, treatment, and course in individuals with juvenile neuronal ceroid lipofuscinosis (JNCL). Data from an ongoing natural history study of JNCL were analyzed using cross-sectional and longitudinal methods. Seizures were evaluated with the Unified Batten Disease Rating Scale, a disease-specific quantitative assessment tool. Eighty-six children (44 males, 42 females) with JNCL were assessed at an average of three annual visits (range 1-11). Eighty-six percent (n=74) experienced at least one seizure, most commonly generalized tonic-clonic, with mean age at onset of 9 years 7 months (SD 2y 10mo). Seizures were infrequent, typically occurring less often than once every 3 months, and were managed with one to two medications for most participants. Valproate (49%, n=36) and levetiracetam (41%, n=30) were the most commonly used seizure medications. Myoclonic seizures occurred infrequently (16%, n=14). Seizure severity did not vary by sex or genotype. Seizures showed mild worsening with increasing age. The neuronal ceroid lipofuscinoses (NCLs) represent a group of disorders unified by neurodegeneration and symptoms of blindness, seizures, motor impairment, and dementia. While NCLs are considered in the differential diagnosis of progressive myoclonus epilepsy, we show that myoclonic seizures are infrequent in JNCL. This highlights the NCLs as consisting of genetically distinct disorders with differing natural history. © 2014 Mac Keith Press.

  4. [18F]fluorodopa PET shows striatal dopaminergic dysfunction in juvenile neuronal ceroid lipofuscinosis.

    PubMed Central

    Ruottinen, H M; Rinne, J O; Haaparanta, M; Solin, O; Bergman, J; Oikonen, V J; Järvelä, I; Santavuori, P

    1997-01-01

    OBJECTIVES: To investigate whether nigrostriatal dopaminergic hypofunction is related to the extrapyramidal symptoms in patients with juvenile neuronal ceroid lipofuscinosis (JNCL). METHODS: Nine patients with JNCL and seven healthy controls were studied using [18F]fluorodopa PET. RESULTS: In the patients with JNCL [18F]fluorodopa uptake (K[i][occ]) in the putamen was 60% of the control mean and the corresponding figure in the caudate nucleus was 79%. There was a weak correlation between putamen K(i)(occ) values and extrapyramidal symptoms of the patients evaluated by the motor part of the unified Parkinson's disease rating scale (r = -0.57, P < 0.05). The overall severity of the disease also displayed a negative correlation with the K(i)(occ) values in the putamen (r = -0.71, P < 0.05). CONCLUSION: In patients with JNCL there was reduced striatal [18F]fluorodopa uptake, which had a modest correlation with extrapyramidal symptoms. Dysfunction of nigrostriatal dopaminergic neurons is therefore not the only cause of the patients' extrapyramidal symptoms, but degenerative changes in other brain areas are also contributory. Images PMID:9219750

  5. Cerebellar defects in a mouse model of juvenile neuronal ceroid lipofuscinosis

    PubMed Central

    Weimer, Jill M.; Benedict, Jared W.; Getty, Amanda L.; Pontikis, Charlie C.; Lim, Ming J.; Cooper, Jonathan D.; Pearce, David A.

    2013-01-01

    Juvenile neuronal ceroid lipofuscinosis (JNCL), or Batten disease, is a neurodegenerative disease resulting from a mutation in CLN3, which presents clinically with visual deterioration, seizures, motor impairments, cognitive decline, hallucinations, loss of circadian rhythm, and premature death in the late-twenties to early-thirties. Using a Cln3 null (Cln3−/−) mouse, we report here several deficits in the cerebellum in the absence of Cln3, including cell loss and early onset motor deficits. Surprisingly, early onset glial activation and selective neuronal loss within the mature fastigial pathway of the deep cerebellar nuclei (DCN), a region critical for balance and coordination, are seen in many regions of the Cln3−/− cerebellum. Additionally, there is a loss of Purkinje cells (PC) in regions of robust Bergmann glia activation in Cln3−/− mice and human JNCL post-mortem cerebellum. Moreover, the Cln3−/− cerebellum had a mis-regulation in granule cell proliferation and maintenance of PC dendritic arborization and spine density. Overall, this study defines a novel multi-faceted, early-onset cerebellar disruption in the Cln3 null brain, including glial activation, cell loss, and aberrant cell proliferation and differentiation. These early alterations in the maturation of the cerebellum could underlie some of the motor deficits and pathological changes seen in JNCL patients. PMID:19230832

  6. Localization of juvenile, but not late-infantile, neuronal ceroid lipofuscinosis on chromosome 16

    SciTech Connect

    Wenliang Yan; Ozelius, L.; Breakefield, X.O.; Gusella, J.F. Harvard Medical School, Boston, MA ); Boustany, R.M.N. ); Konradi, C.; Lerner, T.; Trofatter, J.A.; Haines, J.L. ); Julier, C. )

    1993-01-01

    The neuronal ceroid lipofuscinoses (NCL) are a group of progressive neurodegenerative disorders characterized by the deposition of autofluorescent proteinaceous fingerprint or curvilinear bodies. The authors have found that CLN3, the gene underlying the juvenile form of NCL, is very tightly linked to the dinucleotide repeat marker D16S285 on chromosome 16. Integration of D16S285 into the genetic map of chromosome 16 by using the Centre d'Etude du Polymorphisme Humain panel of reference pedigrees yielded a favored marker order in the CLN3 region of qtel-D16S150-.08-D16S285-.04-D16S148-.02-D16S67-ptel. The most likely location of the disease gene, near D16S285 in the D16S150-D16S148 interval, was favored by odds of greater than 10[sup 4]:1 over the adjacent D16S148-D16S67 interval, which was recently reported as the minimum candidate region. Analysis of D16S285 in pedigrees with late-infantile NCL virtually excluded the CLN3 region, suggesting that these two forms of NCL are genetically distinct. 23 refs., 3 figs., 2 tabs.

  7. Splicing variants in sheep CLN3, the gene underlying juvenile neuronal ceroid lipofuscinosis.

    PubMed

    Oswald, M J; Palmer, D N; Damak, S

    1999-06-01

    Mutations in different genes underlie different forms of the neuronal ceroid lipofuscinoses (NCLs, Batten disease). Subunit c of mitochondrial ATP synthase specifically accumulates in most of them, including the juvenile CLN3 form and a sheep form orthologous to CLN6. Products of these genes are likely to be components of a complex or pathway for subunit c turnover, and their expression may be cross-regulated. Different bands, some with different subcellular distributions, were detected by antisera against different regions of CLN3 on Western blots of sheep tissues. Affected liver blots were the same as controls but a specific 50-kDa band was at higher concentration in affected brain homogenates than in controls. Others have also reported bands reacting differently to different CLN3 antibodies. When the 3' end of sheep CLN3 cDNA was amplified by RT-PCR, four mRNA splicing variants were found. Different CLN3 splicing variants at the 5' end of the human cDNA have been reported. These mRNA splicing variants may account the variation of epitope distribution and the different subcellular locations of the CLN3 gene product(s). The predicted size of the unmodified CLN3 protein is 48 kDa. Significantly higher molecular weight bands may correspond to oligomers of a CLN3 isoform or to a CLN3 isoform tightly bound to another protein. Copyright 1999 Academic Press.

  8. Antigen presenting cell abnormalities in the Cln3(-/-) mouse model of juvenile neuronal ceroid lipofuscinosis.

    PubMed

    Hersrud, Samantha L; Kovács, Attila D; Pearce, David A

    2016-07-01

    Mutations of the CLN3 gene lead to juvenile neuronal ceroid lipofuscinosis (JNCL), an autosomal recessive lysosomal storage disorder that causes progressive neurodegeneration in children and adolescents. There is evidence of immune system involvement in pathology that has been only minimally investigated. We characterized bone marrow stem cell-derived antigen presenting cells (APCs), peritoneal macrophages, and leukocytes from spleen and blood, harvested from the Cln3(-/-) mouse model of JNCL. We detected dramatically elevated CD11c surface levels and increased total CD11c protein in Cln3(-/-) cell samples compared to wild type. This phenotype was specific to APCs and also to a loss of CLN3, as surface levels did not differ from wild type in other leukocyte subtypes nor in cells from two other NCL mouse models. Subcellularly, CD11c was localized to lipid rafts, indicating that perturbation of surface levels is attributable to derangement of raft dynamics, which has previously been shown in Cln3 mutant cells. Interrogation of APC function revealed that Cln3(-/-) cells have increased adhesiveness to CD11c ligands as well as an abnormal secretory pattern that closely mimics what has been previously reported for Cln3 mutant microglia. Our results show that CLN3 deficiency alters APCs, which can be a major contributor to the autoimmune response in JNCL. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Evidence for aberrant astrocyte hemichannel activity in Juvenile Neuronal Ceroid Lipofuscinosis (JNCL).

    PubMed

    Burkovetskaya, Maria; Karpuk, Nikolay; Xiong, Juan; Bosch, Megan; Boska, Michael D; Takeuchi, Hideyuki; Suzumura, Akio; Kielian, Tammy

    2014-01-01

    Juvenile Neuronal Ceroid Lipofuscinosis (JNCL) is a lysosomal storage disease caused by an autosomal recessive mutation in CLN3 that leads to vision loss, progressive cognitive and motor decline, and premature death. Morphological evidence of astrocyte activation occurs early in the disease process and coincides with regions where neuronal loss eventually ensues. However, the consequences of CLN3 mutation on astrocyte function remain relatively ill-defined. Astrocytes play a critical role in CNS homeostasis, in part, by their ability to regulate the extracellular milieu via the formation of extensive syncytial networks coupled by gap junction (GJ) channels. In contrast, unopposed hemichannels (HCs) have been implicated in CNS pathology by allowing the non-discriminant passage of molecules between the intracellular and extracellular milieus. Here we examined acute brain slices from CLN3 mutant mice (CLN3Δex7/8) to determine whether CLN3 loss alters the balance of GJ and HC activity. CLN3Δex7/8 mice displayed transient increases in astrocyte HC opening at postnatal day 30 in numerous brain regions, compared to wild type (WT) animals; however, HC activity steadily decreased at postnatal days 60 and 90 in CLN3Δex7/8 astrocytes to reach levels lower than WT cells. This suggested a progressive decline in astrocyte function, which was supported by significant reductions in glutamine synthetase, GLAST, and connexin expression in CLN3Δex7/8 mice compared to WT animals. Based on the early increase in astrocyte HC activity, CLN3Δex7/8 mice were treated with the novel carbenoxolone derivative INI-0602 to inhibit HCs. Administration of INI-0602 for a one month period significantly reduced lysosomal ceroid inclusions in the brains of CLN3Δex7/8 mice compared to WT animals, which coincided with significant increases in astrocyte GJ communication and normalization of astrocyte resting membrane potential to WT levels. Collectively, these findings suggest that alterations in

  10. Equine neuronal ceroid lipofuscinosis.

    PubMed

    Url, A; Bauder, B; Thalhammer, J; Nowotny, N; Kolodziejek, J; Herout, N; Fürst, S; Weissenböck, H

    2001-04-01

    Neuronal ceroid lipofuscinosis (NCL) is an inherited, neurodegenerative disorder with fatal outcome in humans. It has also been described in some animal species; this is the first report of NCL in equines. Three horses showed developmental retardation, slow movements and loss of appetite at the age of six months. Neurological symptoms, as well as visual failure in one case, were noticed at the age of 1 year. Due to slowly progressing deterioration, euthanasia was indicated 1.5 years after onset of conspicuous behavior. At necropsy, slight flattening of the gyri and discoloring of the brain was noticed. Histopathology revealed eosinophilic, autofluorescent material in the perikarya of neurons throughout the brain and spinal cord. Identical material was found in neurons of retina, submucous and myenteric ganglia, as well as in glial cells. Immunohistochemistry, using antiserum against subunit c of mitochondrial ATP synthase, showed positive signals in neurons and glial cells. Electron microscopical studies revealed fingerprint profiles mixed with rectilinear structures in markedly enlarged lysosomes of neurons and renal tubules, and rectilinear structures mixed with curvilinear bodies in macrophages and lymphocytes of lymph nodes. Thus, our study presents the first occurrence of lysosomal storage disease in horses, further characterized by immunohistochemical and electron microscopical investigations as NCL.

  11. Alterations in striatal dopamine catabolism precede loss of substantia nigra neurons in a mouse model of Juvenile Neuronal Ceroid Lipofuscinosis

    PubMed Central

    Weimer, Jill M.; Benedict, Jared W.; Elshatory, Yasser M.; Short, Douglas W.; Ramirez-Montealegre, Denia; Ryan, Deborah A.; Alexander, Noreen A.; Federoff, Howard J.; Cooper, Jonathan D.; Pearce, David A.

    2016-01-01

    Batten disease, or juvenile neuronal ceroid lipofuscinosis (JNCL), results from mutations in the CLN3 gene. This disorder presents clinically around the age of five years with visual deficits progressing to include seizures, cognitive impairment, motor deterioration, hallucinations, and premature death by the third to forth decade of life. The motor deficits include coordination and gait abnormalities, myoclonic jerks, inability to initiate movements, and spasticity. Previous work from our laboratory has identified an early reduction in catechol-O-methyltransferase (COMT), an enzyme responsible for the efficient degradation of dopamine. Alterations in the kinetics of dopamine metabolism could cause the accumulation of undegraded or unsequestered dopamine leading to the formation of toxic dopamine intermediates. We report an imbalance in the catabolism of dopamine in three month Cln3-/- mice persisting through nine months of age that may be causal to oxidative damage within the striatum at nine months of age. Combined with the previously reported inflammatory changes and loss of post-synaptic D1α receptors, this could facilitate cell loss in striatal projection regions and underlie a general locomotion deficit that becomes apparent at twelve months of age in Cln3-/- mice. This study provides evidence for early changes in the kinetics of COMT in the Cln3-/- mouse striatum, affecting the turnover of dopamine, likely leading to neuron loss and motor deficits. These data provide novel insights into the basis of motor deficits in JNCL and how alterations in dopamine catabolism may result in oxidative damage and localized neuronal loss in this disorder. PMID:17617387

  12. The Neuronal Ceroid-Lipofuscinoses

    ERIC Educational Resources Information Center

    Bennett, Michael J.; Rakheja, Dinesh

    2013-01-01

    The neuronal ceroid-lipofuscinoses (NCL's, Batten disease) represent a group of severe neurodegenerative diseases, which mostly present in childhood. The phenotypes are similar and include visual loss, seizures, loss of motor and cognitive function, and early death. At autopsy, there is massive neuronal loss with characteristic storage in…

  13. The Neuronal Ceroid-Lipofuscinoses

    ERIC Educational Resources Information Center

    Bennett, Michael J.; Rakheja, Dinesh

    2013-01-01

    The neuronal ceroid-lipofuscinoses (NCL's, Batten disease) represent a group of severe neurodegenerative diseases, which mostly present in childhood. The phenotypes are similar and include visual loss, seizures, loss of motor and cognitive function, and early death. At autopsy, there is massive neuronal loss with characteristic storage in…

  14. Altered elemental profiles in neuronal ceroid lipofuscinosis.

    PubMed

    Johansson, E; Lindh, U; Westermarck, T; Heiskala, H; Santavuori, P

    1990-09-01

    The elemental profiles of thrombocytes and mononuclear cells were investigated in five patients with Infantile and eight with Juvenile Neuronal Ceroid Lipofuscinosis. The patients with the infantile form had suffered from the disease for a year and those with the juvenile form for some six years. The thrombocytes exhibited increased concentrations of calcium and magnesium, but the same concentrations of iron and zinc as found in healthy subjects. The mononuclear cells exhibited an increased concentration of iron and a reduced concentration of zinc. The elevated concentrations of magnesium, calcium and iron in the thrombocytes and mononuclear cells may represent the end products of ceroid pigmentation. Five patients with Juvenile and one with Infantile Neuronal Ceroid Lipofuscinosis were treated with antioxidants along with vitamins E, B2 and B6, but this treatment did not affect significantly the concentration of iron in the mononuclear cells. However, selenium was detected in some mononuclear cells in all the patients so treated. This was unexpected since iron (III), being antagonistic to selenium in the form of selenite--which was the antioxidant given--forms a stable complex which cannot be broken down biologically.

  15. Self-Complementary AAV9 Gene Delivery Partially Corrects Pathology Associated with Juvenile Neuronal Ceroid Lipofuscinosis (CLN3).

    PubMed

    Bosch, Megan E; Aldrich, Amy; Fallet, Rachel; Odvody, Jessica; Burkovetskaya, Maria; Schuberth, Kaitlyn; Fitzgerald, Julie A; Foust, Kevin D; Kielian, Tammy

    2016-09-14

    Juvenile neuronal ceroid lipofuscinosis (JNCL) is a fatal lysosomal storage disease caused by autosomal-recessive mutations in CLN3 for which no treatment exists. Symptoms appear between 5 and 10 years of age, beginning with blindness and seizures, followed by progressive cognitive and motor decline and premature death (late teens to 20s). We explored a gene delivery approach for JNCL by generating two self-complementary adeno-associated virus 9 (scAAV9) constructs to address CLN3 dosage effects using the methyl-CpG-binding protein 2 (MeCP2) and β-actin promoters to drive low versus high transgene expression, respectively. This approach was based on the expectation that low CLN3 levels are required for cellular homeostasis due to minimal CLN3 expression postnatally, although this had not yet been demonstrated in vivo One-month-old Cln3(Δex7/8) mice received one systemic (intravenous) injection of scAAV9/MeCP2-hCLN3 or scAAV9/β-actin-hCLN3, with green fluorescent protein (GFP)-expressing viruses as controls. A promoter-dosage effect was observed in all brain regions examined, in which hCLN3 levels were elevated 3- to 8-fold in Cln3(Δex7/8) mice receiving scAAV9/β-actin-hCLN3 versus scAAV9/MeCP2-hCLN3. However, a disconnect occurred between CLN3 levels and disease improvement, because only the scAAV9 construct driving low CLN3 expression (scAAV9/MeCP2-hCLN3) corrected motor deficits and attenuated microglial and astrocyte activation and lysosomal pathology. This may have resulted from preferential promoter usage because transgene expression after intravenous scAAV9/MeCP2-GFP injection was primarily detected in NeuN(+) neurons, whereas scAAV9/β-actin-GFP drove transgene expression in GFAP(+) astrocytes. This is the first demonstration of a systemic delivery route to restore CLN3 in vivo using scAAV9 and highlights the importance of promoter selection for disease modification in juvenile animals. Juvenile neuronal ceroid lipofuscinosis (JNCL) is a fatal lysosomal

  16. Antigen presenting cell abnormalities in the Cln3−/− mouse model of juvenile neuronal ceroid lipofuscinosis

    PubMed Central

    Hersrud, Samantha L.; Kovács, Attila D.; Pearce, David A.

    2016-01-01

    Mutations of the CLN3 gene lead to juvenile neuronal ceroid lipofuscinosis (JNCL), an autosomal recessive lysosomal storage disorder that causes progressive neurodegeneration in children and adolescents. There is evidence of immune system involvement in pathology that has been only minimally investigated. We characterized bone marrow stem cell-derived antigen presenting cells (APCs), peritoneal macrophages, and leukocytes from spleen and blood, harvested from the Cln3−/− mouse model of JNCL. We detected dramatically elevated CD11c surface levels and increased total CD11c protein in Cln3−/− cell samples compared to wild type. This phenotype was specific to APCs and also to a loss of CLN3, as surface levels did not differ from wild type in other leukocyte subtypes nor in cells from two other NCL mouse models. Subcellularly, CD11c was localized to lipid rafts, indicating that perturbation of surface levels is attributable to derangement of raft dynamics, which has previously been shown in Cln3 mutant cells. Interrogation of APC function revealed that Cln3−/− cells have increased adhesiveness to CD11c ligands as well as an abnormal secretory pattern that closely mimics what has been previously reported for Cln3 mutant microglia. Our results show that CLN3 deficiency alters APCs, which can be a major contributor to the autoimmune response in JNCL. PMID:27101989

  17. Linkage disequilibrium between the juvenile neuronal ceroid lipofuscinosis gene and marker loci on chromosome 16p12. 1

    SciTech Connect

    Lerner, T.J.; MacCormack, K.; Gleitsman, J.; Schlumpf, K.; Breakefield, X.O.; Gusella, J.F.; Haines, J.L. )

    1994-01-01

    The neuronal ceroid lipofuscinoses (NCL; Batten disease) are a collection of autosomal recessive disorders characterized by the accumulation of autofluorescent lipopigments in the neurons and other cell types. Clinically, these disorders are characterized by progressive encephalopathy, loss of vision, and seizures. CLN3, the gene responsible for juvenile NCL, has been mapped to a 15-cM region flanked by the marker loci D16S148 and D16S150 on human chromosome 16. CLN2, the gene causing the late-infantile form of NCL (LNCL), is not yet mapped. The authors have used highly informative dinucleoide repeat markers mapping between D16S148 and D16S150 to refine the localization of CLN3 and to test for linkage to CLN2. The authors find significant linkage disequilibrium between CLN3 and the dinucleotide repeat marker loci D16S288 (X[sup 2](7) = 46.5, P < .005), D16S298 (X[sup 2](6) = 36.6, P < .005), and D16S299 (X[sup 2](7) = 73.8, P < .005), and also a novel RFLP marker at the D16S272 locus (X[sup 2](1) = 5.7, P = .02). These markers all map to 16p12.1. The D16S298/D16S299 haplotype [open quotes]5/4[close quotes] is highly overrepresented, accounting for 54% of CLN3 chromosomes as compared with 8% of control chromosomes (X[sup 2] = 117, df = 1, P < .001). Examination of the haplotypes suggests that the CLN3 locus can be narrowed to the region immediately surrounding these markers in 16p12.1. Analysis of D16S299 in LNCL pedigrees supports the previous finding that CLN3 and CLN2 are different genetic loci. This study also indicates that dinucleotide repeat markers play a valuable role in disequilibrium studies. 23 refs., 1 fig., 4 tabs.

  18. Neuronal Ceroid Lipofuscinosis (Batten's Disease)

    PubMed Central

    Gordon, N. S.; Marsden, H. B.; Noronha, M. J.

    1972-01-01

    Four patients are described, who on clinical, histological, and biochemical criteria are considered to be suffering from neuronal ceroid lipofuscinosis. It is suggested that this may be the commonest condition included under the term amaurotic family idiocy. A number of gangliosidoses can be classified on a biochemical basis and considerable advances have been made in identifying the enzyme deficiencies. The aetiology of neuronal ceroid lipofuscinosis is unknown, and it is possible that there is more than one cause. Visual symptoms and signs are not always present. Though generalized convulsions occur at the start of the illness, myoclonus tends increasingly to dominate the clinical picture. An abnormal sensitivity to photic stimulation at a very slow frequency is a suggestive finding. Evidence of cerebral atrophy on air-encephalography favours this diagnosis, as the brain tends to be enlarged in the gangliosidoses. A definite diagnosis can only be made in life by examination of a cortical biopsy. Biochemical analysis will show a normal ganglioside pattern, and histological examination by light and electron microscopy will reveal characteristic changes. An age dependent classification of amaurotic family idiocy is no longer justifiable, and if full investigations are carried out, an increasing number of these patients can be diagnosed as suffering from a specific type of disorder. ImagesFIG. 1FIG. 2 PMID:5023478

  19. Plasma Biomarkers for Neuronal Ceroid Lipofuscinosis

    PubMed Central

    Hersrud, Samantha L.; Geraets, Ryan D.; Weber, Krystal L.; Chan, Chun-Hung; Pearce, David A.

    2015-01-01

    The neuronal ceroid lipofuscinoses (NCLs) are a group of neurodegenerative genetic diseases that primarily affect children and have no known cure. A unified clinical rating scale for the juvenile form of NCL (JNCL) has been developed, but it has not been validated in other subtypes and does not give a true measure of the pathophysiological changes that may be occurring during disease progression. In this study, we have identified candidate biomarkers in blood plasma of NCL disease using multiple proteomic approaches, with the aim of developing a panel of biomarkers that could serve as a metric for therapeutic response. Candidate biomarkers were identified as proteins with levels that significantly differed between patients and controls in both sample sets. The seven candidates identified have previously been associated with neurodegenerative and inflammatory diseases. Multiplex immunoassay based testing was the most efficient and effective evaluation technique and could be employed on a broad scale to track patient response to treatment. PMID:26565144

  20. Neuronal ceroid lipofuscinosis (Batten disease) in Newfoundland

    SciTech Connect

    Frecker, M.F.; Jacob, J.C.; Ives, E.J.

    1994-09-01

    The neuronal ceroid lipofuscinoses (NCL) are a group of recessively inherited neurodegenerative disorders. The most common type found in Newfoundland is late infantile NCL; 1 in 63 of the population is estimated to be a carrier. The incidence has decreased over the years with fewer affected siblings born in families and migration away from smaller communities. For the 30 late infantile cases (24 families), most presented with generalized convulsive seizures; all had curvilinear inclusion bodies in several cell types. The mean age at onset was 2.8 {plus_minus} 0.6 yr and they lived a mean of 7.5 {plus_minus} 2.1 yr. Three of these families have been used to exclude linkage to markers on chromosome 1 and 16. There is one typical juvenile NCL family; it has been used to further define the localization of the gene on chromosome 16p. Genetic counseling for carrier status has been offered in this family. A single case of adult NCL (Kufs) has been identified. Reevaluation of the cases indicated that there are many who have clinical and neuropathological features of both late infantile and juvenile NCL. Unusual findings in these 13 cases (11 families) included the coexistence of both types of inclusion bodies. In patients with juvenile fingerprint inclusion bodies, atypical presentations were delayed milestones at age 8 mo, visual loss before 4 yr, psychomotor retardation before loss of vision and an enhanced response to photic stimulation on EEG. Molecular studies will determine the basis for this heterogeneity. Extensive family histories showed only 53% (19/36) of families were consanguinous or interelated indicating that the frequency of the gene is probably quite high.

  1. Photoreceptor phagosome processing defects and disturbed autophagy in retinal pigment epithelium of Cln3Δex1-6 mice modelling juvenile neuronal ceroid lipofuscinosis (Batten disease)

    PubMed Central

    Wavre-Shapton, Silène T.; Calvi, Alessandra A.; Turmaine, Mark; Seabra, Miguel C.; Cutler, Daniel F.; Futter, Clare E.; Mitchison, Hannah M.

    2015-01-01

    Retinal degeneration and visual impairment are the first signs of juvenile neuronal ceroid lipofuscinosis caused by CLN3 mutations, followed by inevitable progression to blindness. We investigated retinal degeneration in Cln3Δex1-6 null mice, revealing classic ‘fingerprint’ lysosomal storage in the retinal pigment epithelium (RPE), replicating the human disease. The lysosomes contain mitochondrial F0-ATP synthase subunit c along with undigested membranes, indicating a reduced degradative capacity. Mature autophagosomes and basal phagolysosomes, the terminal degradative compartments of autophagy and phagocytosis, are also increased in Cln3Δex1-6 RPE, reflecting disruption to these key pathways that underpin the daily phagocytic turnover of photoreceptor outer segments (POS) required for maintenance of vision. The accumulated autophagosomes have post-lysosome fusion morphology, with undigested internal contents visible, while accumulated phagosomes are frequently docked to cathepsin D-positive lysosomes, without mixing of phagosomal and lysosomal contents. This suggests lysosome-processing defects affect both autophagy and phagocytosis, supported by evidence that phagosomes induced in Cln3Δex1-6-derived mouse embryonic fibroblasts have visibly disorganized membranes, unprocessed internal vesicles and membrane contents, in addition to reduced LAMP1 membrane recruitment. We propose that defective lysosomes in Cln3Δex1-6 RPE have a reduced degradative capacity that impairs the final steps of the intimately connected autophagic and phagocytic pathways that are responsible for degradation of POS. A build-up of degradative organellar by-products and decreased recycling of cellular materials is likely to disrupt processes vital to maintenance of vision by the RPE. PMID:26450516

  2. Genetic heterogeneity in neuronal ceroid lipofuscinosis (NCL): Evidence that the late-infantile subtype (Jansky-Bielschowsky disease; CLN2) is not an allelic form of the juvenile or infantile subtypes

    PubMed Central

    Williams, Ruth; Vesa, Jouni; Järvelä, Irma; McKay, Tristan; Mitchison, Hannah; Hellsten, Elina; Thompson, Andrew; Callen, David; Sutherland, Grant; Luna-Battadano, David; Stallings, Ray; Peltonen, Leena; Gardiner, Mark

    1993-01-01

    The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigment in neurons and other cell types. Inheritance is autosomal recessive. Three main childhood subtypes are recognized: infantile (Haltia-Santavuori disease; MIM 256743), late infantile (Jansky-Bielschowsky disease; MIM 204500), and juvenile (Spielmeyer-Sjögren-Vogt, or Batten, disease; MIM 204200). The gene loci for the juvenile (CLN3) and infantile (CLN1) types have been mapped to human chromosomes 16p and 1p, respectively, by linkage analysis. Linkage analysis of 25 families segregating for late-infantile NCL has excluded these regions as the site of this disease locus (CLN2). The three childhood subtypes of NCL therefore arise from mutations at distinct loci. PMID:8213822

  3. Membrane trafficking and mitochondrial abnormalities precede subunit c deposition in a cerebellar cell model of juvenile neuronal ceroid lipofuscinosis

    PubMed Central

    Fossale, Elisa; Wolf, Pavlina; Espinola, Janice A; Lubicz-Nawrocka, Tanya; Teed, Allison M; Gao, Hanlin; Rigamonti, Dorotea; Cattaneo, Elena; MacDonald, Marcy E; Cotman, Susan L

    2004-01-01

    Background JNCL is a recessively inherited, childhood-onset neurodegenerative disease most-commonly caused by a ~1 kb CLN3 mutation. The resulting loss of battenin activity leads to deposition of mitochondrial ATP synthase, subunit c and a specific loss of CNS neurons. We previously generated Cln3Δex7/8 knock-in mice, which replicate the common JNCL mutation, express mutant battenin and display JNCL-like pathology. Results To elucidate the consequences of the common JNCL mutation in neuronal cells, we used P4 knock-in mouse cerebella to establish conditionally immortalized CbCln3 wild-type, heterozygous, and homozygous neuronal precursor cell lines, which can be differentiated into MAP-2 and NeuN-positive, neuron-like cells. Homozygous CbCln3Δex7/8 precursor cells express low levels of mutant battenin and, when aged at confluency, accumulate ATPase subunit c. Recessive phenotypes are also observed at sub-confluent growth; cathepsin D transport and processing are altered, although enzyme activity is not significantly affected, lysosomal size and distribution are altered, and endocytosis is reduced. In addition, mitochondria are abnormally elongated, cellular ATP levels are decreased, and survival following oxidative stress is reduced. Conclusions These findings reveal that battenin is required for intracellular membrane trafficking and mitochondrial function. Moreover, these deficiencies are likely to be early events in the JNCL disease process and may particularly impact neuronal survival. PMID:15588329

  4. Remote Assessment of Cognitive Function in Juvenile Neuronal Ceroid Lipofuscinosis (Batten disease) – a Pilot Study of Feasibility and Reliability

    PubMed Central

    Ragbeer, Shayne N.; Augustine, Erika F.; Mink, Jonathan W.; Thatcher, Alyssa R.; Vierhile, Amy E.; Adams, Heather R.

    2015-01-01

    Remote technology provides an opportunity to extend the reach of clinical care and research for pediatric rare disease. This pilot study evaluated the feasibility and reliability of neuropsychological evaluation, using remote audiovisual technology, in the assessment of children with juvenile Batten disease. Three children with Batten disease and one healthy sibling completed a standardized cognitive assessment. Results indicated high agreement between an in-person and a remote evaluator, when comparing the subjects’ cognitive test scores. This initial test of remote cognitive assessment suggests it is feasible and reliable in children with pediatric neurodegenerative disease, for whom disease burden may limit travel and access to expert care and/or clinical trials. PMID:26336202

  5. So-called neuronal ceroid lipofuscinosis

    PubMed Central

    Pampiglione, G.; Harden, A.

    1977-01-01

    EEG, ERG, and VEP studies were carried out in 60 children with verified neuronal storage of ceroid/lipofuscin-like material. Comparing and contrasting the EEG/ERG/VER features of each child during the symptomatic phase of the disease, three distinct main groups could be recognised: (1) Progressive diminution in amplitude of the EEG and VEP beginning about the age of 2 years was seen in seven children, and all phasic cerebral activity was unrecordable at 3-4 years of age; the clinical onset with regression in skills began at 1-2 years of age; (2) Large amplitude irregular slow activity and polyphasic spikes appeared in 27 children in whom characteristic discharges were elicited at low rates of photic stimulation (grossly enlarged VEP); the clinical onset was around 3 years of age with an occasional seizure and some clumsiness; (3) Runs of slow wave and spike complexes were seen in the EEG of 10 children with a small or absent VEP; the clinical onset with visual failure began around 5-7 years of age. In the remaining 16 children, the EEG and the clinical features fell into much smaller groups, possibly of rarer type. The ERG became unrecordable at an early symptomatic phase in all 60 children. The present findings suggest that such umbrella terms as neuronal ceroid lipofuscinosis or Batten's disease, which imply a single disease entity, are misleading. Neurophysiological investigations can help in early identification of these separate conditions. When the biochemical basis of these disorders becomes fully understood a more rational nomenclature will be possible. PMID:874509

  6. A frame shift mutation in canine TPP1 (the ortholog of human CLN2) in a juvenile Dachshund with neuronal ceroid lipofuscinosis.

    PubMed

    Awano, Tomoyuki; Katz, Martin L; O'Brien, Dennis P; Sohar, Istvan; Lobel, Peter; Coates, Joan R; Khan, Shahnawaz; Johnson, Gayle C; Giger, Urs; Johnson, Gary S

    2006-11-01

    The neuronal ceroid lipofuscinoses (NCLs) are inherited lysosomal storage diseases characterized by progressive neuropathy and the accumulation of autofluorescent cytoplasmic granules. Clinical signs of a new canine NCL began in a 9-month-old male Dachshund with vomiting, mental dullness, and loss of previously learned commands and rapidly progressed to include disorientation, ataxia, visual deficits, generalized myoclonic seizures, and death at 12 months of age. Neurons throughout the CNS contained autofluorescent storage granules that stained with periodic acid-Schiff and Luxol fast blue stains. Electron microscopy revealed that the storage granule contents consisted of curvilinear-appearing material characteristic of human late infantile NCL caused by CLN2 mutations. Nucleotide sequence analysis of canine TPP1, the ortholog of human CLN2, revealed a single nucleotide deletion in exon 4 which predicted a frame shift with a premature stop codon. Brain tissue from the affected dog lacked detectable activity of the tripeptidyl-peptidase enzyme encoded by TPP1, whereas the specific activities of 15 other lysosomal enzymes were higher than those in the brains of three control dogs. The affected Dachshund was homozygous for the mutant c.325delC allele, his sire and dam were heterozygotes, and 181 unrelated dogs, including 77 Dachshunds, were all homozygous for the wild-type allele. A DNA assay that detects the mutant allele will help Dachshund breeders avoid producing affected puppies in future generations. Furthermore, this Dachshund NCL may prove to be a useful model for studying the pathogenesis of neurodegeneration in human late infantile NCL and for evaluating novel therapeutic interventions for this disease.

  7. Linkage analysis of late-infantile neuronal ceroid-lipofuscinosis

    SciTech Connect

    Sharp, J.; Wheeler, R.B.; Jaervelae, I.

    1995-06-05

    The neuronal ceroid-lipofuscinoses (NCL) are a group of neurodegenerative disorders with an autosomal-recessive pattern of inheritance. There are 3 main categories of childhood NCL, namely, infantile, late-infantile, and juvenile NCL. These can be distinguished on the basis of age of onset, clinical course, and histopathology. A number of variant forms of NCL have also been mapped to chromosome areas 1p32 and 16p12, respectively. The gene for late-infantile NCL (LINCL), CLN2, has been excluded from both these loci, but its location is as yet unknown. Recently, CLN5, the gene for the Finnish variant form of LINCL, was mapped to 13q21.1-32. Using the 3 microsatellite markers which were most tightly linked to CLN5, we have excluded CLN2 from this region using a subset of 17 families. Thus, CLN2 represents a fourth distinct genetic locus involved in the pathogenesis of NCL. 6 refs., 1 fig., 1 tab.

  8. Diagnosis of neuronal ceroid lipofuscinosis: mutation detection strategies.

    PubMed

    Getty, Amanda L; Rothberg, Paul G; Pearce, David A

    2007-11-01

    The neuronal ceroid lipofuscinoses (NCL) are a group of rare genetically inherited neurodegenerative disorders in children. These diseases are classified by age of onset (congenital, infantile, late-infantile, juvenile and adult-onset) and by the gene bearing mutations (CLN10/CTSD, CLN1/PPT1, CLN2/TPP1, CLN3, CLN5, CLN6, CLN7/MFSD8 and CLN8). Enzyme activity assays are helpful in identifying several of these disorders; however confirmation of the mutation in the gene causing these diseases is vital for definitive diagnosis. There exists considerable heterogeneity in the NCLs as a whole and within each type of NCL both in phenotype (disease manifestation and progression) and genotype (type of mutation), which complicates NCL diagnosis. In order to streamline the diagnostic process, the age of symptom onset, geography and/or ethnicity, and enzyme activity may be considered together. However, these ultimately serve to guide targeting the correct route to genetic confirmation of an NCL through mutational analysis. Herein, an effective protocol to diagnose NCLs using these criteria is presented.

  9. The neuronal ceroid-lipofuscinoses: a historical introduction.

    PubMed

    Haltia, Matti; Goebel, Hans H

    2013-11-01

    The neuronal ceroid-lipofuscinoses (Batten disease) collectively constitute one of the most common groups of inherited childhood onset neurodegenerative disorders, and have also been identified in many domestic and laboratory animals. The group of human neuronal ceroid-lipofuscinoses currently comprises 14 genetically distinct disorders, mostly characterised by progressive mental, motor and visual deterioration with onset in childhood or adolescence. Abnormal autofluorescent, electron-dense granules accumulate in the cytoplasm of nerve cells, and this storage process is associated with selective destruction and loss of neurons in the brain and retina. The present paper outlines nearly 200 years of clinical, neuropathological, biochemical and molecular genetic research, gradually leading, since 1995, to the identification of 13 different genes and over 360 mutations that underlie these devastating brain disorders and form the basis of a new classification system. These genes are evidently of vital importance for the normal development and maintenance of cerebral neurons. Elucidation of their functions and interactions in health and disease is a prerequisite for the identification of possible therapeutic targets, but may also further our understanding of the basic mechanisms of neurodegeneration and ageing. An account is also given of the development of international cooperation and free access electronic resources facilitating NCL research. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Partial correction of the CNS lysosomal storage defect in a mouse model of juvenile neuronal ceroid lipofuscinosis by neonatal CNS administration of an adeno-associated virus serotype rh.10 vector expressing the human CLN3 gene.

    PubMed

    Sondhi, Dolan; Scott, Emma C; Chen, Alvin; Hackett, Neil R; Wong, Andrew M S; Kubiak, Agnieszka; Nelvagal, Hemanth R; Pearse, Yewande; Cotman, Susan L; Cooper, Jonathan D; Crystal, Ronald G

    2014-03-01

    Juvenile neuronal ceroid lipofuscinosis (JNCL or CLN3 disease) is an autosomal recessive lysosomal storage disease resulting from mutations in the CLN3 gene that encodes a lysosomal membrane protein. The disease primarily affects the brain with widespread intralysosomal accumulation of autofluorescent material and fibrillary gliosis, as well as the loss of specific neuronal populations. As an experimental treatment for the CNS manifestations of JNCL, we have developed a serotype rh.10 adeno-associated virus vector expressing the human CLN3 cDNA (AAVrh.10hCLN3). We hypothesized that administration of AAVrh.10hCLN3 to the Cln3(Δex7/8) knock-in mouse model of JNCL would reverse the lysosomal storage defect, as well as have a therapeutic effect on gliosis and neuron loss. Newborn Cln3(Δex7/8) mice were administered 3 × 10(10) genome copies of AAVrh.10hCLN3 to the brain, with control groups including untreated Cln3(Δex7/8) mice and wild-type littermate mice. After 18 months, CLN3 transgene expression was detected in various locations throughout the brain, particularly in the hippocampus and deep anterior cortical regions. Changes in the CNS neuronal lysosomal accumulation of storage material were assessed by immunodetection of subunit C of ATP synthase, luxol fast blue staining, and periodic acid-Schiff staining. For all parameters, Cln3(Δex7/8) mice exhibited abnormal lysosomal accumulation, but AAVrh.10hCLN3 administration resulted in significant reductions in storage material burden. There was also a significant decrease in gliosis in AAVrh.10hCLN3-treated Cln3(Δex7/8) mice, and a trend toward improved neuron counts, compared with their untreated counterparts. These data demonstrate that AAVrh.10 delivery of a wild-type cDNA to the CNS is not harmful and instead provides a partial correction of the neurological lysosomal storage defect of a disease caused by a lysosomal membrane protein, indicating that this may be an effective therapeutic strategy for JNCL and

  11. Methodology of clinical research in rare diseases: development of a research program in juvenile neuronal ceroid lipofuscinosis (JNCL) via creation of a patient registry and collaboration with patient advocates

    PubMed Central

    de Blieck, Elisabeth A.; Augustine, Erika F.; Marshall, Frederick J.; Adams, Heather; Cialone, Jennifer; Dure, Leon; Kwon, Jennifer M.; Newhouse, Nicole; Rose, Katherine; Rothberg, Paul G.; Vierhile, Amy; Mink, Jonathan W.

    2013-01-01

    Introduction Juvenile neuronal ceroid lipofuscinosis (JNCL; Batten disease) is a rare, inherited, fatal lysosomal storage childhood disorder. True for many rare diseases, there are no treatments that impact the course of JNCL. The University of Rochester Batten Center’s (URBC) mission is to find treatments to slow, halt, or prevent JNCL. Objectives Our initial objective was to develop clinical research infrastructure preparatory to clinical trials, establish a JNCL research cohort, construct a disease-specific clinical outcome measure, and validate a non-invasive diagnostic sampling method. The long-term objective is to design and implement JNCL clinical trials. Methods The Unified Batten Disease Rating Scale (UBDRS) was developed. The Batten Disease Support and Research Association (BDSRA) referred participants; annual BDSRA meetings provided a mobile research setting for registry enrollment and UBDRS piloting. Neuropsychological examinations were performed, enabling external validation of the UBDRS. Buccal epithelial cell collection for genotyping was introduced. Telemedicine for remote UBDRS assessment was piloted. Results The registry enrolled 198 families representing 237 children with NCL. The UBDRS was piloted, validated and has been used to collect natural history data from 120 subjects. Funding and regulatory approval were obtained for a recently launched phase II clinical trial. Several additional lines of inquiry were reported. Conclusion The registry and BDSRA collaboration have enabled development of a clinical rating scale, natural history and neuropsychological studies, and genetic studies for disease confirmation. This work highlights an approach for preparatory natural history research and infrastructure development needed to facilitate efficient implementation of clinical trials in rare diseases. PMID:23628560

  12. Altered sensitivity of cerebellar granule cells to glutamate receptor overactivation in the Cln3Δex7/8-knock-in mouse model of juvenile neuronal ceroid lipofuscinosis

    PubMed Central

    Finn, Rozzy; Kovács, Attila D.; Pearce, David A.

    2011-01-01

    The juvenile onset form of neuronal ceroid lipofuscinoses (JNCL) is a recessively inherited lysosomal storage disorder characterized by progressive neurodegeneration. JNCL results from mutations in the CLN3 gene that encodes a lysosomal membrane protein with unknown function. Utilizing a Cln3-knock-out mouse model of JNCL that was created on the 129S6/SvEv genetic background, we have previously demonstrated that CLN3-deficient cerebellar granule cells (CGCs) have a selectively increased sensitivity to AMPA-type glutamate receptor-mediated toxicity. Our recent findings that CGCs from 129S6/SvEv and C57BL/6J wild type (WT) mice have significant differences in glutamate receptor expression and in excitotoxic vulnerability indicated that the genetic background possibly have a strong influence on how glutamate receptor function is dysregulated in CLN3-deficient neurons. Indeed, here we show that in the Cln3Δex7/8-knock-in mouse model, that is on the C57BL/6J genetic background, mimics the most frequent mutation observed in JNCL patients and considered a null mutant, the sensitivity of CGCs to both AMPA- and NMDA-type glutamate receptor overactivations is altered. Cultured wild type and Cln3Δex7/8 CGCs were equally sensitive to AMPA toxicity after 2 or 3 weeks in vitro, whereas the subunit-selective AMPA receptor agonist, CPW-399, induced significantly more cell death in mature, 3-week-old Cln3Δex7/8 cultures. NMDA receptor-mediated toxicity changed during in vitro development: Cln3Δex7/8 CGCs were less sensitive to high concentration of NMDA after 2 weeks in culture but became more vulnerable than their WT counterparts after 3 weeks in vitro. Abnormally altered glutamate receptor function in the cerebellum may result in motor deficits, and we confirmed that 7-week-old Cln3Δex7/8 mice, similarly to Cln3-knock-out mice, have a motor coordination deficit as measured by an accelerating rotarod. Our results demonstrate altered glutamate receptor function in Cln3Δex7

  13. MRI Brain Volume Measurements in Infantile Neuronal Ceroid Lipofuscinosis

    PubMed Central

    Baker, Eva H.; Levin, Sondra W.; Zhang, Zhongjian; Mukherjee, Anil B.

    2016-01-01

    Background Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating neurodegenerative storage disease caused by palmitoyl-protein thioesterase-1 (PPT1) deficiency. PPT1 deficiency impairs degradation of palmitoylated proteins (constituents of ceroid) by lysosomal hydrolases. Consequent lysosomal ceroid accumulation leads to neuronal injury, resulting in rapid neurodegeneration and childhood demise. As part of a project studying treatment benefits of a combination of cysteamine bitartrate and N-acetylcysteine, we made serial measurements of patients’ brain volumes using MRI. Methods Ten INCL patients participating in a treatment/follow-up study underwent brain MRI that included high resolution T1-weighted images. After manual placement of a mask delineating the surface of the brain, a maximum-likelihood classifier was applied to determine total brain volume, further subdivided as cerebrum, cerebellum, brainstem, and thalamus. Patients’ brain volumes were compared to those of a normal population. Results Major subdivisions of the brain followed similar trajectories with different timing. The cerebrum demonstrated early, rapid volume loss, and may never have been normal postnatally. The thalamus dropped out of the normal range around age 6 months, cerebellum around age 2 years, and brainstem around age 3 years. Discussion Rapid cerebral volume loss was expected based upon previous qualitative reports. Because our study did not include a non-treatment arm, and because progression of brain volumes in INCL has not previously been quantified, we could not determine whether our intervention had a beneficial effect on brain volumes. However, the level of quantitative detail in this study allows it to serve as a reference for evaluation of future therapeutic interventions. PMID:27765741

  14. A new simple enzyme assay for pre- and postnatal diagnosis of infantile neuronal ceroid lipofuscinosis (INCL) and its variants

    PubMed Central

    Voznyi, Y; Keulemans, J; Mancini, G; Catsman-Berrevoet..., C; Young, E; Winchester, B; Kleijer, W; van Diggelen, O P

    1999-01-01

    Palmitoyl-protein thioesterase (PPT) deficiency was recently shown to be the primary defect in infantile neuronal ceroid lipofuscinosis (INCL). The available enzyme assay is complicated and impractical for diagnostic use and is, in practice, unavailable. We have developed a new fluorimetric assay for PPT based on the sensitive fluorochrome 4-methylumbelliferone. This PPT assay is simple, sensitive, and robust and will facilitate the definition of the full clinical spectrum associated with a deficiency of PPT. PPT activity was readily detectable in fibroblasts, leucocytes, lymphoblasts, amniotic fluid cells, and chorionic villi, but was profoundly deficient in these tissues from INCL patients. Similarly, a deficiency of PPT was shown in patients with the variant juvenile NCL with GROD. These results show that rapid pre- and postnatal diagnosis can be performed with this new enzyme assay for PPT.


Keywords: infantile neuronal ceroid lipofuscinosis; CLN1; palmitoyl-protein thioesterase; enzyme analysis PMID:10874636

  15. Application of chromosome 16 markers in the differential diagnosis of neuronal ceroid-lipofuscinosis

    SciTech Connect

    Taschner, P.E.M.; Vos, N. de; Breuning, M.H.

    1995-06-05

    Accurate diagnosis of neuronal ceroid lipofuscinosis (NCL) is important for a correct prognosis of the disease and for genetic counseling. Up to now, no direct diagnostic test has been available for NCL. The clinical diagnosis is made on the basis of symptoms, neurophysiological, neuroradiological, and specific lipopigment pattern data. Recent advances in the genetics of NCL have enabled us to use polymorphic DNA markers linked to the CLN1 and CLN3 loci as a tool in the differential diagnosis of NCL. We have applied genetic analysis with polymorphic DNA markers flanking the CLN3 gene on chromosome 16 to two consanguineous families in which NCL occurs. In the first family, which is of Turkish extraction, two patients suffering from a protracted form of juvenile NCL previously had been diagnosed with juvenile NCL. Haplotypes from this family indicate that the patients and their healthy sibling are haplo-identical, suggesting that this protracted form of juvenile NCL is not linked to the CLN3 locus. In the second family, which is Moroccan origin, one patient suffers from the early juvenile variant of NCL (Lake-Cavanagh). In this family, the patient and one of the healthy siblings have identical haplotypes, excluding linkage of early juvenile NCL to the CLN3 locus on 16p12.1-11.2. Therefore, these cases from different populations demonstrate that haplotype analysis can be used as an additional method to exclude the diagnosis of juvenile NCL. 21 refs., 4 figs., 1 tab.

  16. Neuronal ceroid-lipofuscinosis and hydrocephalus in a chihuahua.

    PubMed

    Kuwamura, M; Hattori, R; Yamate, J; Kotani, T; Sasai, K

    2003-05-01

    A two-year-old, female chihuahua presented with a six-month history of visual dysfunction. Computed tomography revealed dilation of the lateral ventricles in the central nervous system (CNS). The dog was tentatively diagnosed as having hydrocephalus and a month later was euthanased at the owner's request. The skull was expanded and dome-like in shape and an open fontanelle was observed on postmortem examination. Histologically, swollen neurons possessing yellowish pigment granules in the cytoplasm were observed throughout the CNS. These storage materials stained positively with periodic acid Schiff, Schmorl method for lipofuscin and oil red O for lipid, and showed autofluorescence under fluorescence microscopy. Ultrastructurally, the storage materials consisted of dense lamellar structures. This case was unique in having ceroid-lipofuscinosis in association with hydrocephalus.

  17. Neuronal ceroid lipofuscinosis in a mallard duck (Anas platyrhynchos).

    PubMed

    Evans, Erika E; Jones, Michael P; Crews, Amanda J; Newkirk, Kim

    2012-03-01

    A 3-year-old male, hybrid mallard duck (Anas platyrhynchos) was presented with a 2-year history of progressive, ascending paresis and paralysis. On presentation, the bird was in sternal recumbency and displayed intermittent focal seizures and intention tremors. Proprioceptive deficits and absent withdrawal reflexes were observed in both pelvic limbs, wing extension was limited, and reflexes were diminished bilaterally. Other findings included emaciation and dehydration. Results of a complete blood count and plasma biochemical analysis revealed anemia, hypoproteinemia, hypoglycemia, and hyperuricemia. Radiographs were unremarkable and results of an Aspergillus antibody were weakly positive. The duck went into cardiopulmonary arrest and died approximately 1 hour after initiating treatment with intravenous crystalloid fluids. A postmortem diagnosis of neuronal ceroid lipofuscinosis (NCL) was made based on the presence of neuronal granular cytoplasmic material that was autofluorescent and stained with periodic acid-Schiff and Luxol fast blue. To our knowledge, this is only the second case report of NCL in an avian species and the first in waterfowl.

  18. Diagnosis and misdiagnosis of adult neuronal ceroid lipofuscinosis (Kufs disease)

    PubMed Central

    Staropoli, John F.; Carpenter, Stirling; Oliver, Karen L.; Kmoch, Stanislav; Anderson, Glenn W.; Damiano, John A.; Hildebrand, Michael S.; Sims, Katherine B.; Cotman, Susan L.; Bahlo, Melanie; Smith, Katherine R.; Cadieux-Dion, Maxime; Cossette, Patrick; Jedličková, Ivana; Přistoupilová, Anna; Mole, Sara E.

    2016-01-01

    Objective: To critically re-evaluate cases diagnosed as adult neuronal ceroid lipofuscinosis (ANCL) in order to aid clinicopathologic diagnosis as a route to further gene discovery. Methods: Through establishment of an international consortium we pooled 47 unsolved cases regarded by referring centers as ANCL. Clinical and neuropathologic experts within the Consortium established diagnostic criteria for ANCL based on the literature to assess each case. A panel of 3 neuropathologists independently reviewed source pathologic data. Cases were given a final clinicopathologic classification of definite ANCL, probable ANCL, possible ANCL, or not ANCL. Results: Of the 47 cases, only 16 fulfilled the Consortium's criteria of ANCL (5 definite, 2 probable, 9 possible). Definitive alternate diagnoses were made in 10, including Huntington disease, early-onset Alzheimer disease, Niemann-Pick disease, neuroserpinopathy, prion disease, and neurodegeneration with brain iron accumulation. Six cases had features suggesting an alternate diagnosis, but no specific condition was identified; in 15, the data were inadequate for classification. Misinterpretation of normal lipofuscin as abnormal storage material was the commonest cause of misdiagnosis. Conclusions: Diagnosis of ANCL remains challenging; expert pathologic analysis and recent molecular genetic advances revealed misdiagnoses in >1/3 of cases. We now have a refined group of cases that will facilitate identification of new causative genes. PMID:27412140

  19. Perioperative care of a patient with neuronal ceroid lipofuscinoses

    PubMed Central

    Kako, Hiromi; Martin, David P.; Tobias, Joseph D.

    2013-01-01

    The neuronal ceroid lipofuscinoses (NCL) are a group of inherited, autosomal recessive, and progressive neurodegenerative diseases, which result from an enzymatic defect or the deficiency of a transmembrane protein, leading to the accumulation of lipopigments (lipofuscin) in various tissues. NCL results in the impairment of function in several end-organs including the central nervous system with loss of cognitive and motor function, myoclonus, and intractable seizures. Additional involvement includes the cardiovascular system with arrhythmias and bradycardia as well as impairment of thermoregulation leading to perioperative hypothermia. Given the complexity of the end-organ involvement and the progressive nature of the disorder, the anesthetic care of such patients can be challenging. Till date, there are a limited number of reports regarding the anesthetic management of patients with NCL. We present an 18-year-old patient with NCL who required anesthetic care during replacement of a vagal nerve stimulator. Previous reports of anesthetic care for these patients are reviewed, the end-organ involvement of NCL discussed, and options for anesthetic care presented. PMID:24015141

  20. CLN2 Disease (Classic Late Infantile Neuronal Ceroid Lipofuscinosis).

    PubMed

    Kohlschütter, Alfried; Schulz, Angela

    2016-06-01

    CLN2 disease is an inherited metabolic storage disorder caused by the deficiency of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1). The disease affects mainly the brain and the retina and is characterized by progressive dysfunction of the central nervous system, leading to dementia, epilepsy, loss of motor function and blindness. The classical late infantile type begins at around three years of age with epilepsy and/or a standstill of psychomotor development, followed by a rapid loss of all abilities and death in childhood. A late onset form in a small proportion of patients starts at the age of 4 to 10 years, but also leads to severe neurological deterioration. The deficiency of TPP1 causes the lysosomal accumulation of a material called ceroid lipofuscin. The natural substrate of TPP1 is not known, nor is the connection between storage process and neurodegeneration, which is characterized by loss of neurons. Among various experimental approaches to treatment, enzyme replacement therapy (ERT) and gene therapy have developed remarkably. Enzyme delivery through the cerebrospinal fluid led to wide distribution of enzyme activity in the brain and to attenuated neuropathology and disease progression in a TPP1-deficient mouse model as well as in a natural TPP1-deficient dog model. Safety of the intrathecal delivery, pharmacokinetics, and tissue distribution of the administered enzyme studied in non-human primates were encouraging, and a phase I/II clinical trial for intraventricular ERT in CLN2 patients is ongoing. A second approach uses intracerebral injection of viral vectors containing normal coding segments of the CLN2 gene. In a CLN2 mouse model, this procedure resulted in cerebral enzyme expression, reduced brain pathology and increased survival. A small number of patients have been treated the same way using an AAV2-vector for gene transfer to the brain. Although there were no serious adverse events unequivocally attributable to the vector used, there were

  1. A Homozygous Mutation in KCTD7 Links Neuronal Ceroid Lipofuscinosis to the Ubiquitin-Proteasome System

    PubMed Central

    Staropoli, John F.; Karaa, Amel; Lim, Elaine T.; Kirby, Andrew; Elbalalesy, Naser; Romansky, Stephen G.; Leydiker, Karen B.; Coppel, Scott H.; Barone, Rosemary; Xin, Winnie; MacDonald, Marcy E.; Abdenur, Jose E.; Daly, Mark J.; Sims, Katherine B.; Cotman, Susan L.

    2012-01-01

    Neuronal ceroid lipofuscinosis (NCL) is a genetically heterogeneous group of lysosomal diseases that collectively compose the most common Mendelian form of childhood-onset neurodegeneration. It is estimated that ∼8% of individuals diagnosed with NCL by conservative clinical and histopathologic criteria have been ruled out for mutations in the nine known NCL-associated genes, suggesting that additional genes remain unidentified. To further understand the genetic underpinnings of the NCLs, we performed whole-exome sequencing on DNA samples from a Mexican family affected by a molecularly undefined form of NCL characterized by infantile-onset progressive myoclonic epilepsy (PME), vision loss, cognitive and motor regression, premature death, and prominent NCL-type storage material. Using a recessive model to filter the identified variants, we found a single homozygous variant, c.550C>T in KCTD7, that causes a p.Arg184Cys missense change in potassium channel tetramerization domain-containing protein 7 (KCTD7) in the affected individuals. The mutation was predicted to be deleterious and was absent in over 6,000 controls. The identified variant altered the localization pattern of KCTD7 and abrogated interaction with cullin-3, a ubiquitin-ligase component and known KCTD7 interactor. Intriguingly, murine cerebellar cells derived from a juvenile NCL model (CLN3) showed enrichment of endogenous KCTD7. Whereas KCTD7 mutations have previously been linked to PME without lysosomal storage, this study clearly demonstrates that KCTD7 mutations also cause a rare, infantile-onset NCL subtype designated as CLN14. PMID:22748208

  2. Disruption of PPT1 or PPT2 causes neuronal ceroid lipofuscinosis in knockout mice

    PubMed Central

    Gupta, Praveena; Soyombo, Abigail A.; Atashband, Armita; Wisniewski, Krystyna E.; Shelton, John M.; Richardson, James A.; Hammer, Robert E.; Hofmann, Sandra L.

    2001-01-01

    PPT1 and PPT2 encode two lysosomal thioesterases that catalyze the hydrolysis of long chain fatty acyl CoAs. In addition to this function, PPT1 (palmitoyl-protein thioesterase 1) hydrolyzes fatty acids from modified cysteine residues in proteins that are undergoing degradation in the lysosome. PPT1 deficiency in humans causes a neurodegenerative disorder, infantile neuronal ceroid lipofuscinosis (also known as infantile Batten disease). In the current work, we engineered disruptions in the PPT1 and PPT2 genes to create “knockout” mice that were deficient in either enzyme. Both lines of mice were viable and fertile. However, both lines developed spasticity (a “clasping” phenotype) at a median age of 21 wk and 29 wk, respectively. Motor abnormalities progressed in the PPT1 knockout mice, leading to death by 10 mo of age. In contrast, the majority of PPT2 mice were alive at 12 mo. Myoclonic jerking and seizures were prominent in the PPT1 mice. Autofluorescent storage material was striking throughout the brains of both strains of mice. Neuronal loss and apoptosis were particularly prominent in PPT1-deficient brains. These studies provide a mouse model for infantile neuronal ceroid lipofuscinosis and further suggest that PPT2 serves a role in the brain that is not carried out by PPT1. PMID:11717424

  3. First Japanese variant of late infantile neuronal ceroid lipofuscinosis caused by novel CLN6 mutations.

    PubMed

    Sato, Ryo; Inui, Takehiko; Endo, Wakaba; Okubo, Yukimune; Takezawa, Yusuke; Anzai, Mai; Morita, Hiroyuki; Saitsu, Hirotomo; Matsumoto, Naomichi; Haginoya, Kazuhiro

    2016-10-01

    The clinical phenotypes of neuronal ceroid lipofuscinoses (NCLs) have been determined based on the age of onset and clinical symptoms. NCLs with onset between age 2 and 4years are known as late infantile neuronal ceroid lipofuscinoses (LINCLs). The clinical features of LINCLs include visual loss and progressive myoclonus epilepsy (PME) characterized by myoclonus, seizures, ataxia, and both mental and motor deterioration. There have been reports of several genes associated with LINCLs, with mutations in the CLN6 gene reported to cause variant forms of LINCLs (vLINCLs). Here, we report the first Japanese vLINCL caused by novel CLN6 mutations, found in a patient diagnosed by whole-exome sequencing. Visual acuity in our patient was preserved until the early teens. It remains to be elucidated if preserved visual function is related to the novel mutations of CLN6. Our case reveals the efficacy of whole-exome sequencing for examination of PMEs and highlights the existence of the CLN6 mutation in the Japanese population. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  4. Successive neuron loss in the thalamus and cortex in a mouse model of infantile neuronal ceroid lipofuscinosis

    PubMed Central

    Kielar, Catherine; Maddox, Lucy; Bible, Ellen; Pontikis, Charlie C; Macauley, Shannon L; Griffey, Megan A; Wong, Michael; Sands, Mark S; Cooper, Jonathan D

    2007-01-01

    Infantile neuronal ceroid lipofuscinosis (INCL) is caused by deficiency of the lysosomal enzyme, palmitoyl protein thioesterase 1 (PPT1). We have investigated the onset and progression of pathological changes in Ppt1-deficient mice (Ppt1−/−) and the development of their seizure phenotype. Surprisingly, cortical atrophy and neuron loss occurred only late in disease progression, but were preceded by localized astrocytosis within individual thalamic nuclei and the progressive loss of thalamic neurons that relay different sensory modalities to the cortex. This thalamic neuron loss occurred first within the visual system and only subsequently in auditory and somatosensory relay nuclei or the inhibitory reticular thalamic nucleus. The loss of granule neurons and GABAergic interneurons followed in each corresponding cortical region, before the onset of seizure activity. These findings provide novel evidence for successive neuron loss within the thalamus and cortex in Ppt1−/− mice, revealing the thalamus as an important early focus of INCL pathogenesis. PMID:17046272

  5. Mutational analysis of the defective protease in classic late-infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder.

    PubMed Central

    Sleat, D E; Gin, R M; Sohar, I; Wisniewski, K; Sklower-Brooks, S; Pullarkat, R K; Palmer, D N; Lerner, T J; Boustany, R M; Uldall, P; Siakotos, A N; Donnelly, R J; Lobel, P

    1999-01-01

    The late-infantile form of neuronal ceroid lipofuscinosis (LINCL) is a progressive and ultimately fatal neurodegenerative disease of childhood. The defective gene in this hereditary disorder, CLN2, encodes a recently identified lysosomal pepstatin-insensitive acid protease. To better understand the molecular pathology of LINCL, we conducted a genetic survey of CLN2 in 74 LINCL families. In 14 patients, CLN2 protease activities were normal and no mutations were identified, suggesting other forms of NCL. Both pathogenic alleles were identified in 57 of the other 60 LINCL families studied. In total, 24 mutations were associated with LINCL, comprising six splice-junction mutations, 11 missense mutations, 3 nonsense mutations, 3 small deletions, and 1 single-nucleotide insertion. Two mutations were particularly common: an intronic G-->C transversion in the invariant AG of a 3' splice junction, found in 38 of 115 alleles, and a C-->T transition in 32 of 115 alleles, which prematurely terminates translation at amino acid 208 of 563. An Arg-->His substitution was identified, which was associated with a late age at onset and protracted clinical phenotype, in a number of other patients originally diagnosed with juvenile NCL. PMID:10330339

  6. Palmitoyl protein thioesterase (PPT) localizes into synaptosomes and synaptic vesicles in neurons: implications for infantile neuronal ceroid lipofuscinosis (INCL).

    PubMed

    Lehtovirta, M; Kyttälä, A; Eskelinen, E L; Hess, M; Heinonen, O; Jalanko, A

    2001-01-01

    A deficiency of palmitoyl protein thioesterase (PPT) leads to the neurodegenerative disease infantile neuronal ceroid lipofuscinosis (INCL), which is characterized by an almost complete loss of cortical neurons. PPT expressed in COS-1 cells is recognized by the mannose-6-phosphate receptor (M6PR) and is routed to lysosome, but a substantial fraction of PPT is secreted. We have here determined the neuronal localization of PPT by confocal microscopy, cryoimmunoelectron microscopy and cell fractionation. In mouse primary neurons and brain tissue, PPT is localized in synaptosomes and synaptic vesicles but not in lysosomes. Furthermore, in polarized epithelial Caco-2 cells, PPT is localized exclusively to the basolateral site, in contrast to the classical lysosomal enzyme, aspartylglucosaminidase (AGA), which is localized in the apical site. The current data imply that PPT has a role outside the lysosomes in the brain and may be associated with synaptic functioning. This finding opens a new route to study the neuropathological events associated with INCL.

  7. Progress in the Development of Small Molecule Therapeutics for the Treatment of Neuronal Ceroid Lipofuscinoses (NCLs).

    PubMed

    Kinarivala, Nihar; Trippier, Paul C

    2016-05-26

    The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited and incurable neurodegenerative disorders primarily afflicting the pediatric population. Current treatment regimens offer only symptomatic relief and do not target the underlying cause of the disease. Although the underlying pathophysiology that drives disease progression is unknown, several small molecules have been identified with diverse mechanisms of action that provide promise for the treatment of this devastating disease. This review aims to summarize the current cellular and animal models available for the identification of potential therapeutics and presents the current state of knowledge on small molecule compounds that demonstrate in vitro and/or in vivo efficacy across the NCLs with an emphasis on targets of action.

  8. Seizure Susceptibility, Phenotype, and Resultant Growth Delay in the nclf and mnd Mouse Models of Neuronal Ceroid Lipofuscinoses

    PubMed Central

    Kriscenski-Perry, Elizabeth; Kovács, Attila D.; Pearce, David A.

    2014-01-01

    We examined flurothyl gas-induced seizure latencies and phenotype in 2 mouse models of neuronal ceroid lipofuscinoses: the nclf (Cln6 mutant) variant late-infantile model and the mnd (Cln8 mutant) Northern epilepsy model. Mnd mice on postnatal days 35 to 42 had increased latency to loss of posture compared with wild-type controls. Nclf, mnd, and wild-type mice on postnatal days 21 days to 25 displayed similar latency profiles during repeated seizure induction (kindling) and retesting; seizure phenotypes were different, however. Kindled wild-type mice re-exposed to flurothyl after a 28-day recovery displayed brainstem generalized seizures exclusively. Neuronal ceroid lipofuscinoses mutants demonstrated a lack of brainstem seizures at retesting after 28 days. Repeated induction of generalized seizures delayed weight gain in both nclf and mnd mice compared with wild-type mice. These and our previous results suggest abnormal seizure-related neuronal connectivity and/or plasticity are shared characteristics of the neuronal ceroid lipofuscinoses. PMID:23838029

  9. Neuronal ceroid lipofuscinosis in a 31-year-old woman presenting as biventricular heart failure with restrictive features.

    PubMed

    Fealey, Michael E; Edwards, William D; Grogan, Martha; Orszulak, Thomas A

    2009-01-01

    A 31-year-old woman presented with dyspnea and left-sided chest discomfort and was found to have biventricular heart failure with impaired ventricular filling. Clinically, she was thought to have restrictive cardiomyopathy or constrictive pericarditis. Transmission electron microscopy of myocardial tissue unexpectedly revealed crosshatched, curvilinear, and fingerprint depositions, which were characteristic for neuronal ceroid lipofuscinosis. Cardiac involvement by this inherited disorder is discussed in light of the findings in this patient and in 15 other reported cases.

  10. Homozygous PPT1 Splice Donor Mutation in a Cane Corso Dog With Neuronal Ceroid Lipofuscinosis.

    PubMed

    Kolicheski, A; Barnes Heller, H L; Arnold, S; Schnabel, R D; Taylor, J F; Knox, C A; Mhlanga-Mutangadura, T; O'Brien, D P; Johnson, G S; Dreyfus, J; Katz, M L

    2017-01-01

    A 10-month-old spayed female Cane Corso dog was evaluated after a 2-month history of progressive blindness, ataxia, and lethargy. Neurologic examination abnormalities indicated a multifocal lesion with primarily cerebral and cerebellar signs. Clinical worsening resulted in humane euthanasia. On necropsy, there was marked astrogliosis throughout white matter tracts of the cerebrum, most prominently in the corpus callosum. In the cerebral cortex and midbrain, most neurons contained large amounts of autofluorescent storage material in the perinuclear area of the cells. Cerebellar storage material was present in the Purkinje cells, granular cell layer, and perinuclear regions of neurons in the deep nuclei. Neuronal ceroid lipofuscinosis (NCL) was diagnosed. Whole genome sequencing identified a PPT1c.124 + 1G>A splice donor mutation. This nonreference assembly allele was homozygous in the affected dog, has not previously been reported in dbSNP, and was absent from the whole genome sequences of 45 control dogs and 31 unaffected Cane Corsos. Our findings indicate a novel mutation causing the CLN1 form of NCL in a previously unreported dog breed. A canine model for CLN1 disease could provide an opportunity for therapeutic advancement, benefiting both humans and dogs with this disorder. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  11. Pharmacological Effects on Ceroid Lipofuscin and Neuronal Structure in Cln3 (∆ex7/8) Mouse Brain Cultures.

    PubMed

    Brenneman, Douglas E; Pearce, David A; Kovacs, Attila; DeFrees, Shawn

    2017-08-15

    Juvenile Batten disease (JBD) is an inherited disorder that is characterized by the development of blindness, seizures, and progressive motor, psychiatric, and cognitive impairment. A model of JBD expressing the predominant human mutation (Cln3 (∆ex7/8) ) has been explored. Dissociated brain cultures from Cln3 (∆ex7/8) knock-in mice were compared to wild type (WT) for effects on granules of ceroid lipofuscin (CL) and neuronal structure. Utilizing high content image analysis of CL granules identified with antibodies to mitochondrial ATP synthase subunit c or tripeptidyl peptidase-1, significant increases in the areas for both immunoreactive granules were observed in Cln3 (∆ex7/8) cultures in comparison to WT. CL granules also exhibit autofluorescence at 488 and 560 nm, and the areas of these autofluorescent spots were found to be significantly increased in Cln3 (∆ex7/8) cultures in comparison to WT. Progressive increases in CL granule area in Cln3 (∆ex7/8) cultures were observed during culture development. Because current therapies for JBD provide only symptomatic support, a therapeutic strategy has been explored based on the observations that JBD-related tissues are deficient in β-galactosyl ceramide. Treatment of cultures for 40 h with a potent analog of β-galactosyl ceramide (SNB-4050) produced significant decreases in CL granule area in the Cln3 (∆ex7/8) cultures; whereas identical studies on WT cultures produced no detectible changes. Significant decreases in average neurite length and neurite branch point number were also observed in the Cln3 (∆ex7/8) cultures that were attenuated by treatment with 1 nM SNB-4050. These studies indicate Cln3 (∆ex7/8) brain cultures may be useful to screen therapeutic agents for treatment of JBD.

  12. The Chihuahua dog: A new animal model for neuronal ceroid lipofuscinosis CLN7 disease?

    PubMed

    Faller, Kiterie M E; Bras, Jose; Sharpe, Samuel J; Anderson, Glenn W; Darwent, Lee; Kun-Rodrigues, Celia; Alroy, Joseph; Penderis, Jacques; Mole, Sara E; Gutierrez-Quintana, Rodrigo; Guerreiro, Rita J

    2016-04-01

    Neuronal ceroid lipofuscinoses (NCLs) are a group of incurable lysosomal storage disorders characterized by neurodegeneration and accumulation of lipopigments mainly within the neurons. We studied two littermate Chihuahua dogs presenting with progressive signs of blindness, ataxia, pacing, and cognitive impairment from 1 year of age. Because of worsening of clinical signs, both dogs were euthanized at about 2 years of age. Postmortem examination revealed marked accumulation of autofluorescent intracellular inclusions within the brain, characteristic of NCL. Whole-genome sequencing was performed on one of the affected dogs. After sequence alignment and variant calling against the canine reference genome, variants were identified in the coding region or splicing regions of four previously known NCL genes (CLN6, ARSG, CLN2 [=TPP1], and CLN7 [=MFSD8]). Subsequent segregation analysis within the family (two affected dogs, both parents, and three relatives) identified MFSD8:p.Phe282Leufs13*, which had previously been identified in one Chinese crested dog with no available ancestries, as the causal mutation. Because of the similarities of the clinical signs and histopathological changes with the human form of the disease, we propose that the Chihuahua dog could be a good animal model of CLN7 disease.

  13. Imaging gene delivery in a mouse model of congenital neuronal ceroid lipofuscinosis.

    PubMed

    Pike, L S; Tannous, B A; Deliolanis, N C; Hsich, G; Morse, D; Tung, C-H; Sena-Esteves, M; Breakefield, X O

    2011-12-01

    Adeno-associated virus (AAV)-mediated gene replacement for lysosomal disorders have been spurred by the ability of some serotypes to efficiently transduce neurons in the brain and by the ability of lysosomal enzymes to cross-correct among cells. Here, we explored enzyme replacement therapy in a knock-out mouse model of congenital neuronal ceroid lipofuscinosis (NCL), the most severe of the NCLs in humans. The missing protease in this disorder, cathepsin D (CathD) has high levels in the central nervous system. This enzyme has the potential advantage for assessing experimental therapy in that it can be imaged using a near-infrared fluorescence (NIRF) probe activated by CathD. Injections of an AAV2/rh8 vector-encoding mouse CathD (mCathD) into both cerebral ventricles and peritoneum of newborn knock-out mice resulted in a significant increase in lifespan. Successful delivery of active CathD by the AAV2/rh8-mCathD vector was verified by NIRF imaging of mouse embryonic fibroblasts from knock-out mice in culture, as well as by ex vivo NIRF imaging of the brain and liver after gene transfer. These studies support the potential effectiveness and imaging evaluation of enzyme replacement therapy to the brain and other organs in CathD null mice via AAV-mediated gene delivery in neonatal animals.

  14. Granulin Knock Out Zebrafish Lack Frontotemporal Lobar Degeneration and Neuronal Ceroid Lipofuscinosis Pathology

    PubMed Central

    Solchenberger, Barbara; Russell, Claire; Kremmer, Elisabeth; Haass, Christian; Schmid, Bettina

    2015-01-01

    Loss of function mutations in granulin (GRN) are linked to two distinct neurological disorders, frontotemporal lobar degeneration (FTLD) and neuronal ceroid lipofuscinosis (NCL). It is so far unknown how a complete loss of GRN in NCL and partial loss of GRN in FTLD can result in such distinct diseases. In zebrafish, there are two GRN homologues, Granulin A (Grna) and Granulin B (Grnb). We have generated stable Grna and Grnb loss of function zebrafish mutants by zinc finger nuclease mediated genome editing. Surprisingly, the grna and grnb single and double mutants display neither spinal motor neuron axonopathies nor a reduced number of myogenic progenitor cells as previously reported for Grna and Grnb knock down embryos. Additionally, grna−/−;grnb−/− double mutants have no obvious FTLD- and NCL-related biochemical and neuropathological phenotypes. Taken together, the Grna and Grnb single and double knock out zebrafish lack any obvious morphological, pathological and biochemical phenotypes. Loss of zebrafish Grna and Grnb might therefore either be fully compensated or only become symptomatic upon additional challenge. PMID:25785851

  15. Oral cysteamine bitartrate and N-acetylcysteine for patients with infantile neuronal ceroid lipofuscinosis: a pilot study.

    PubMed

    Levin, Sondra W; Baker, Eva H; Zein, Wadih M; Zhang, Zhongjian; Quezado, Zenaide M N; Miao, Ning; Gropman, Andrea; Griffin, Kurt J; Bianconi, Simona; Chandra, Goutam; Khan, Omar I; Caruso, Rafael C; Liu, Aiyi; Mukherjee, Anil B

    2014-08-01

    Infantile neuronal ceroid lipofuscinosis is a devastating neurodegenerative lysosomal storage disease caused by mutations in the gene (CLN1 or PPT1) encoding palmitoyl-protein thioesterase-1 (PPT1). We have previously reported that phosphocysteamine and N-acetylcysteine mediate ceroid depletion in cultured cells from patients with this disease. We aimed to assess whether combination of oral cysteamine bitartrate and N-acetylcysteine is beneficial for patients with neuronal ceroid lipofuscinosis. Children between 6 months and 3 years of age with infantile neuronal ceroid lipofuscinosis with any two of the seven most lethal PPT1 mutations were eligible for inclusion in this pilot study. All patients were recruited from physician referrals. Patients received oral cysteamine bitartrate (60 mg/kg per day) and N-acetylcysteine (60 mg/kg per day) and were assessed every 6-12 months until they had an isoelectric electroencephalogram (EEG, attesting to a vegetative state) or were too ill to travel. Patients were also assessed by electroretinography, brain MRI and magnetic resonance spectroscopy (MRS), and electron microscopic analyses of leukocytes for granular osmiophilic deposits (GRODs). Children also underwent physical and neurodevelopmental assessments on the Denver scale. Outcomes were compared with the reported natural history of infantile neuronal ceroid lipofuscinosis and that of affected older siblings. This trial is registered with ClinicalTrials.gov, number NCT00028262. Between March 14, 2001, and June 30, 2012, we recruited ten children with infantile neuronal ceroid lipofuscinosis; one child was lost to follow-up after the first visit and nine patients (five girls and four boys) were followed up for 8 to 75 months. MRI showed abnormalities similar to those in previous reports; brain volume and N-acetyl aspartic acid (NAA) decreased steadily, but no published quantitative MRI or MRS studies were available for comparison. None of the children acquired new

  16. Canine neuronal ceroid lipofuscinoses: Promising models for preclinical testing of therapeutic interventions.

    PubMed

    Katz, Martin L; Rustad, Eline; Robinson, Grace O; Whiting, Rebecca E H; Student, Jeffrey T; Coates, Joan R; Narfstrom, Kristina

    2017-08-30

    The neuronal ceroid lipofuscinoses (NCLs) are devastating inherited progressive neurodegenerative diseases, with most forms having a childhood onset of clinical signs. The NCLs are characterized by progressive cognitive and motor decline, vision loss, seizures, respiratory and swallowing impairment, and ultimately premature death. Different forms of NCL result from mutations in at least 13 genes. The clinical signs of some forms overlap significantly, so genetic testing is the only way to definitively determine which form an individual patient suffers from. At present, an effective treatment is available for only one form of NCL. Evidence of NCL has been documented in over 20 canine breeds and in mixed-breed dogs. To date, 12 mutations in 8 different genes orthologous to the human NCL genes have been found to underlie NCL in a variety of dog breeds. A Dachshund model with a null mutation in one of these genes is being utilized to investigate potential therapeutic interventions, including enzyme replacement and gene therapies. Demonstration of the efficacy of enzyme replacement therapy in this model led to successful completion of human clinical trials of this treatment. Further research into the other canine NCLs, with in-depth characterization and understanding of the disease processes, will likely lead to the development of successful therapeutic interventions for additional forms of NCL, for both human patients and animals with these disorders. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. The role of nonsense-mediated decay in neuronal ceroid lipofuscinosis

    PubMed Central

    Miller, Jake N.; Chan, Chun-Hung; Pearce, David A.

    2013-01-01

    Neuronal ceroid lipofuscinosis (NCL), commonly referred to as Batten disease, is a group of autosomal recessive neurodegenerative diseases of childhood characterized by seizures, blindness, motor and cognitive decline and premature death. Currently, there are over 400 known mutations in 14 different genes, leading to five overlapping clinical variants of NCL. A large portion of these mutations lead to premature stop codons (PTCs) and are predicted to predispose mRNA transcripts to nonsense-mediated decay (NMD). Nonsense-mediated decay is associated with a number of other genetic diseases and is an important regulator of disease pathogenesis. We contend that NMD targets PTCs in NCL gene transcripts for degradation. A number of PTC mutations in CLN1, CLN2 and CLN3 lead to a significant decrease in mRNA transcripts and a corresponding decrease in protein levels and function in patient-derived lymphoblast cell lines. Inhibiting NMD leads to an increased transcript level, and where protein function is known, increased activity. Treatment with read-through drugs also leads to increased protein function. Thus, NMD provides a promising therapeutic target that would allow read-through of transcripts to enhance protein function and possibly ameliorate Batten disease pathogenesis. PMID:23539563

  18. A Case-controlled Investigation of Pain Experience and Sensory Function in Neuronal Ceroid Lipofuscinosis

    PubMed Central

    Barney, Chantel C.; Hoch, John; Byiers, Breanne; Dimian, Adele; Symons, Frank J.

    2014-01-01

    Objectives This case-control study explored pain experience and expression among individuals with Neuronal Ceroid Lipofuscinosis (NCL) through parental report, tactile-sensory testing, and infrared thermography (IRT). Methods Individuals with NCL (n=8; M age= 14.8 years) and their unaffected siblings (n=8;M age 23.5 years) were characterized in terms of pain response to a brief tactile sensory test (light touch, Von Frey monofilament). During sensory testing, behavioral expression was measured using the Battens Observational Pain Scale (BOPS) and infrared thermography (IRT) was used to quantify changes in skin/eye temperature. Results Individuals with NCL experienced pain frequently and from multiple sources that negatively impacted their lives. Individuals with NCL were reactive to the sensory testing as indexed by significant increased IRT temperature change (p<.001). Across combined sensory conditions, individuals with NCL were significantly more reactive (BOPS total score) to sensory testing compared to siblings (p< .05). Similarly, IRT difference scores between sensory conditions revealed a significant increase in temperature for individuals with NCL compared to siblings (p<.001). Discussion Ongoing reported pain was a problem for the individuals with NCL in this sample. Increased pain expression during the repeated Von Frey filament suggests that the pathophysiology of the ongoing pain may be centrally mediated. PMID:25569218

  19. Novel mutations in the CLN6 gene causing a variant late infantile neuronal ceroid lipofuscinosis.

    PubMed

    Teixeira, Carla A; Espinola, Janice; Huo, Liang; Kohlschütter, Johannes; Persaud Sawin, Dixie-Ann; Minassian, Berge; Bessa, Carlos J P; Guimarães, A; Stephan, Dietrich A; Sá Miranda, Maria Clara; MacDonald, Marcy E; Ribeiro, Maria Gil; Boustany, Rose-Mary N

    2003-05-01

    The neuronal ceroid lipofuscinoses (NCLs) are a heterogeneous group of autosomal recessive neurodegenerative diseases comprising Batten and other related diseases plus numerous variants. They are characterized by progressive neuronal cell death. The CLN6 gene was recently identified, mutations in which cause one of the variant late infantile forms of NCL (vLINCL). We describe four novel mutations in the CLN6 gene. This brings the total number of CLN6 mutations known to 11 in 38 families. This suggests that the CLN6 gene may be highly mutable. An American patient of Irish/French/Native American origin was heterozygous for a 4-bp insertion (c.267_268insAACG) in exon 3. The other allele had a point mutation (c.898T>C) in exon 7 resulting in a W300R amino acid change. Two Trinidadian siblings of Indian origin were homozygous for a mutation at the 5' donor splice site of exon 4 (IVS4+1G>T), affecting the first base of the invariant GT at the beginning of intron 4. The fourth novel mutation, a double deletion of 4 bp and 1 bp in exon 7 (c.829_832delGTCG;c.837delG), was identified in a Portuguese patient heterozygous for the I154del Portuguese CLN6 mutation. Four of the 11 mutations identified are in exon 4. Three Portuguese patients with clinical profiles similar to CLN6 patients without defects in CLN6 or other known NCL genes are described. We conclude the following: 1) the CLN6 gene may be a highly mutable gene; 2) exon 4 must code for a segment of the protein crucial for function; 3) vLINCL disease in Portugal is genetically heterogeneous; 4) the I154del accounts for 81.25% of affected CLN6 Portuguese alleles; and 5) three vLINCL Portuguese patients may have defects in a new NCL gene.

  20. The Novel Neuronal Ceroid Lipofuscinosis Gene MFSD8 Encodes a Putative Lysosomal Transporter

    PubMed Central

    Siintola, Eija ; Topcu, Meral ; Aula, Nina ; Lohi, Hannes ; Minassian, Berge A. ; Paterson, Andrew D. ; Liu, Xiao-Qing ; Wilson, Callum ; Lahtinen, Ulla ; Anttonen, Anna-Kaisa ; Lehesjoki, Anna-Elina 

    2007-01-01

    The late-infantile–onset forms are the most genetically heterogeneous group among the autosomal recessively inherited neurodegenerative disorders, the neuronal ceroid lipofuscinoses (NCLs). The Turkish variant was initially considered to be a distinct genetic entity, with clinical presentation similar to that of other forms of late-infantile–onset NCL (LINCL), including age at onset from 2 to 7 years, epileptic seizures, psychomotor deterioration, myoclonus, loss of vision, and premature death. However, Turkish variant LINCL was recently found to be genetically heterogeneous, because mutations in two genes, CLN6 and CLN8, were identified to underlie the disease phenotype in a subset of patients. After a genomewide scan with single-nucleotide–polymorphism markers and homozygosity mapping in nine Turkish families and one Indian family, not linked to any of the known NCL loci, we mapped a novel variant LINCL locus to chromosome 4q28.1-q28.2 in five families. We identified six different mutations in the MFSD8 gene (previously denoted “MGC33302”), which encodes a novel polytopic 518–amino acid membrane protein that belongs to the major facilitator superfamily of transporter proteins. MFSD8 is expressed ubiquitously, with several alternatively spliced variants. Like the majority of the previously identified NCL proteins, MFSD8 localizes mainly to the lysosomal compartment. However, the function of MFSD8 remains to be elucidated. Analysis of the genome-scan data suggests the existence of at least three more genes in the remaining five families, further corroborating the great genetic heterogeneity of LINCLs. PMID:17564970

  1. Autofluorescence and infrared retinal imaging in patients and obligate carriers with neuronal ceroid lipofuscinosis.

    PubMed

    Kelly, John P; Weiss, Avery H; Rowell, Gus; Seigel, Gail M

    2009-12-01

    To measure fundus autofluorescence (FAF) in patients and obligate carriers with Neuronal Ceroid Lipofuscinosis (NCL) and document fundus abnormalities in NCL patients using standard retinal photography and confocal infra-red (IR) imaging. Twenty-seven patients with NCL, 50 obligate carriers of NCL, and 19 controls were imaged in IR and FAF modes by a confocal scanning laser opthalmoscope (HRA II, Heidelberg-Engineering, Inc). FAF intensities were referenced to the mean and standard deviation at the optic disk to remove inter-subject variance and then quantified along the horizontal and vertical meridians. For NCL subjects, FAF images were successfully obtained in 16 eyes (9 of 27 subjects). Of these, 11 eyes had severely reduced or extinguished FAF and 5 eyes (3 subjects) could be analyzed along the meridians. An NCL subject with bilateral bull's eye maculopathy showed overall increased FAF, the remaining 3 eyes had advanced retinal degeneration and showed reduced FAF. Four patterns of macular disease were observed: 1) bull's eye atrophy 2) retinal pigment epithelium (RPE) dropout without pigmentary alterations, 3) RPE dropout with pigmentary alterations, 4) RPE dropout with pigmentary alterations and retinal flecks. Standard photography revealed focal retinal flecks in addition to severe retinal atrophy, RPE dropout, pigmentary clumping, and constricted vessels. Linear striations near the optic disc were highlighted by IR imaging. Topographical comparison of images demonstrated the focal flecks were not hyperfluorescent while the linear striations showed slight increases in FAF. For obligate carriers, FAF profiles were similar to controls with a mild increase in mean FAF intensity. Patients with NCL show increases in retinal fluorophores in early stages and decreases in FAF in late stages of the disease. Obligate carriers of NCL have mildly elevated FAF but this finding is not a specific measure of the carrier state.

  2. Electroclinical spectrum of the neuronal ceroid lipofuscinoses associated with CLN6 mutations

    PubMed Central

    Gilioli, Isabella; Invernizzi, Federica; Sofia, Vito; Fugnanesi, Valeria; Morbin, Michela; Chiapparini, Luisa; Granata, Tiziana; Binelli, Simona; Scaioli, Vidmer; Garavaglia, Barbara; Nardocci, Nardo; Berkovic, Samuel F.; Franceschetti, Silvana

    2015-01-01

    Objectives: To describe the clinical and neurophysiologic patterns of patients with neuronal ceroid lipofuscinoses associated with CLN6 mutations. Methods: We reviewed the features of 11 patients with different ages at onset. Results: Clinical disease onset occurred within the first decade of life in 8 patients and in the second and third decades in 3. All children presented with progressive cognitive regression associated with ataxia and pyramidal and extrapyramidal signs. Recurrent seizures, visual loss, and myoclonus were mostly reported after a delay from onset; 7 children were chairbound and had severe dementia less than 4 years from onset. One child, with onset at 8 years, had a milder course. Three patients with a teenage/adult onset presented with a classic progressive myoclonic epilepsy phenotype that was preceded by learning disability in one. The EEG background was slow close to disease onset in 7 children, and later showed severe attenuation; a photoparoxysmal response (PPR) was present in all. The 3 teenage/adult patients had normal EEG background and an intense PPR. Early attenuation of the electroretinogram was seen only in children with onset younger than 5.5 years. Somatosensory evoked potentials were extremely enlarged in all patients. Conclusions: In all patients, multifocal myoclonic jerks and seizures were a key feature, but myoclonic seizures were an early and prominent sign in the teenage/adult form only. Conversely, the childhood-onset form was characterized by initial and severe cognitive impairment coupled with electroretinogram and EEG attenuation. Cortical hyperexcitability, shown by the PPR and enlarged somatosensory evoked potentials, was a universal feature. PMID:26115733

  3. Mutated CTSF in adult-onset neuronal ceroid lipofuscinosis and FTD

    PubMed Central

    van der Zee, Julie; Mariën, Peter; Crols, Roeland; Van Mossevelde, Sara; Dillen, Lubina; Perrone, Federica; Engelborghs, Sebastiaan; Verhoeven, Jo; D'aes, Tine; Ceuterick-De Groote, Chantal; Sieben, Anne; Versijpt, Jan; Cras, Patrick; Martin, Jean-Jacques

    2016-01-01

    Objective: To investigate the molecular basis of a Belgian family with autosomal recessive adult-onset neuronal ceroid lipofuscinosis (ANCL or Kufs disease [KD]) with pronounced frontal lobe involvement and to expand the findings to a cohort of unrelated Belgian patients with frontotemporal dementia (FTD). Methods: Genetic screening in the ANCL family and FTD cohort (n = 461) was performed using exome sequencing and targeted massive parallel resequencing. Results: We identified a homozygous mutation (p.Ile404Thr) in the Cathepsin F (CTSF) gene cosegregating in the ANCL family. No other mutations were found that could explain the disease in this family. All 4 affected sibs developed motor symptoms and early-onset dementia with prominent frontal features. Two of them evolved to akinetic mutism. Disease presentation showed marked phenotypic variation with the onset ranging from 26 to 50 years. Myoclonic epilepsy in one of the sibs was suggestive for KD type A, while epilepsy was not present in the other sibs who presented with clinical features of KD type B. In a Belgian cohort of unrelated patients with FTD, the same heterozygous p.Arg245His mutation was identified in 2 patients who shared a common haplotype. Conclusions: A homozygous CTSF mutation was identified in a recessive ANCL pedigree. In contrast to the previous associations of CTSF with KD type B, our findings suggest that CTSF genetic testing should also be considered in patients with KD type A as well as in early-onset dementia with prominent frontal lobe and motor symptoms. PMID:27668283

  4. Comparative study of cerebellar degeneration in canine neuroaxonal dystrophy, cerebellar cortical abiotrophy, and neuronal ceroid-lipofuscinosis.

    PubMed

    Nibe, Kazumi; Nakayama, Hiroyuki; Uchida, Kazuyuki

    2010-11-01

    The cerebellar lesions of three dogs with canine neuroaxonal dystrophy (NAD), one dog with cerebellar cortical abiotrophy (CCA), and 4 dogs with neuronal ceroid-lipofuscinosis (NCL) were examined to understand their pathogeneses. Purkinje cell loss was most severe in the vermis of a dog with CCA, and granule cell loss was most prominent in the cerebellar hemisphere of dogs with NCL. Immunohistochemically, CD3-and HLA-DR-positive cells were most frequent in the dogs with NCL, and moderate in dogs with NAD, but not in a dog with CCA. The number of cleaved caspase 3-positive cells was prominent in a dog with CCA, but no significant in the dogs with NAD. The results indicate different pathway of neuronal loss of these canine neuronal disorders.

  5. Photosensitivity is an early marker of neuronal ceroid lipofuscinosis type 2 disease.

    PubMed

    Specchio, Nicola; Bellusci, Marcello; Pietrafusa, Nicola; Trivisano, Marina; de Palma, Luca; Vigevano, Federico

    2017-08-01

    This study aimed to identify early clinical, magnetic resonance imaging (MRI), and electroencephalographic (EEG) characteristics of neuronal ceroid lipofuscinosis type 2 (CLN2) disease to enable early diagnosis, thus providing the key to early treatment, and optimized care and outcomes. Retrospective clinical chart review of a series of patients diagnosed with CLN2 disease from 2005 to 2015 at a single center in Italy. Clinical, MRI, and EEG findings were reviewed. A total of 14 patients were included. For the whole group, median (range) age at disease onset was 3.0 (2.0-3.8) years. Epilepsy was the most commonly reported presenting symptom (in 50% [seven of 14] of patients), occurring at the age of 3.2 (2.6-3.8) years. First seizure was myoclonic in 36% (five of 14) of patients, followed by generalized tonic-clonic in 29% (4 of 14), atonic in 22% (three of 14), and focal with motor signs in 14% (two of 14). All patients walked independently at the age of 12.0 (11.0-18.0) months, but delayed speech or regression of acquired verbal skills was present in 100% of patients at 3 years. EEGs revealed a photoparoxysmal response (PPR) on intermittent photic stimulation in 93% (13 of 14) of patients. PPR was present from the first EEG, which was performed at 3.6 (3.1-4.0) years, in 43% (six of 14) of patients; it was documented at low (1-3 Hz) stimulation frequencies in 69% (nine of 13) and took the form of a flash-per-flash response in 69% (nine of 13). First brain MRI at the age of 3.8 (3.0-5.1) years revealed cerebellar atrophy in 100% (14 of 14) of patients and alteration of the periventricular white matter signal in the posterior hemispheric region in 79% (11 of 14). Early photosensitivity (typically PPR at low stimulation frequencies of 1-3 Hz) is a hallmark of CLN2 disease. This diagnosis should be considered in a child presenting with any type of seizure, and particularly if it is accompanied by delayed speech and/or ataxia or MRI abnormalities (posterior white

  6. First-trimester diagnosis of infantile neuronal ceroid lipofuscinosis (INCL) using PPT enzyme assay and CLN1 mutation analysis.

    PubMed

    de Vries, B B; Kleijer, W J; Keulemans, J L; Voznyi, Y V; Franken, P F; Eurlings, M C; Galjaard, R J; Losekoot, M; Catsman-Berrevoets, C E; Breuning, M H; Taschner, P E; van Diggelen, O P

    1999-06-01

    Infantile neuronal ceroid lipofuscinosis (INCL) is a progressive neurodegenerative disorder in childhood which is caused by the deficiency of the lysosomal palmitoyl-protein thioesterase (PPT) encoded by the CLN1 gene. In a pregnancy at risk for INCL, chorionic villi (CV) were studied using a novel fluorometric PPT enzyme assay in combination with mutation-analysis of the CLN1 gene. The PPT activity in chorionic villi was found to be deficient and homozygosity for the C451T mutation in CLN1 was found. The pregnancy was terminated and the PPT deficiency was confirmed in cultured CV cells as well as in the cultured fetal skin fibroblasts. This report shows the first early prenatal diagnosis of INCL performed by fluorometric enzyme analysis and mutation analysis of the CLN1 gene.

  7. Detection of eight novel palmitoyl protein thioesterase (PPT) mutations underlying infantile neuronal ceroid lipofuscinosis (INCL;CLN1).

    PubMed

    Salonen, T; Järvelä, I; Peltonen, L; Jalanko, A

    2000-01-01

    The infantile form of neuronal ceroid lipofuscinosis (INCL; CLN1) is the earliest onset form of the neuronal ceroid lipofuscinoses (NCL), a group of progressive encephalopathies of children. INCL is caused by mutations in the palmitoyl protein thioesterase (PPT) gene, and we report here eight novel INCL mutations in PPT. Five of the mutations, c.456C>A, c.162-163insA, c.174-175delG, c.774-775insA, and a splice acceptor mutation IVS1-2A>G in intron 1, caused the generation of a premature STOP codon either directly or after a frameshift. One mutation was a three-bp insertion in exon 2 (c. 132-133insTGT) leading to insertion of one extra cysteine (Ser44-insCys-Cys45), and another mutation, a 3-bp deletion in exon 3 (c.249-251delCTT), led to deletion of Phe84 in PPT. A splice acceptor mutation IVS6-1G>T in intron 6 can be predicted to cause skipping of exon 7 in PPT. All of these novel mutations were associated with the classical phenotype of INCL, with the first symptoms starting around 12 months of age. The severe phenotypes could be explained by the nature of the novel mutations: five are predicted to lead to premature translational termination, thus abolishing the active site of PPT, and three will probably cause a misfolding of the nascent polypeptide. Thirty-five percent (7/20) of the disease alleles in these 11 families contained the most prevalent c.451C>T missense mutation outside Finland [Das et al., 1998]. Consequently, 31 different mutations underlying INCL have been found so far, the majority leading to classical INCL. Copyright 2000 Wiley-Liss, Inc.

  8. The novel Cln1(R151X) mouse model of infantile neuronal ceroid lipofuscinosis (INCL) for testing nonsense suppression therapy.

    PubMed

    Miller, Jake N; Kovács, Attila D; Pearce, David A

    2015-01-01

    The neuronal ceroid lipofuscinoses (NCLs), also known as Batten disease, are a group of autosomal recessive neurodegenerative disorders in children characterized by the progressive onset of seizures, blindness, motor and cognitive decline and premature death. Patients with mutations in CLN1 primarily manifest with infantile NCL (INCL or Haltia-Santavuori disease), which is second only to congenital NCL for its age of onset and devastating progression. CLN1 encodes a lysosomal enzyme, palmitoyl-protein thioesterase 1 (PPT1). Nonsense mutations in CLN1 account for 52.3% of all disease causing alleles in infantile NCL, the most common of which worldwide is the p.R151X mutation. Previously, we have shown how nonsense-mediated decay is involved in the degradation of CLN1 mRNA transcripts containing the p.R151X mutation in human lymphoblast cell lines. We have also shown how the read-through drugs gentamicin and ataluren (PTC124) increase CLN1 (PPT1) enzyme activity. Here, we provide the initial characterization of the novel Cln1(R151X) mouse model of infantile neuronal ceroid lipofuscinosis that we have generated. This nonsense mutation model recapitulates the molecular, histological and behavioral phenotypes of the human disease. Cln1(R151X) mice showed a significant decrease in Cln1 mRNA level and PPT1 enzyme activity, accumulation of autofluorescent storage material, astrocytosis and microglial activation in the brain. Behavioral characterization of Cln1(R151X) mice at 3 and 5 months of age revealed significant motor deficits as measured by the vertical pole and rotarod tests. We also show how the read-through compound ataluren (PTC124) increases PPT1 enzyme activity and protein level in Cln1(R151X) mice in a proof-of-principle study. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. The novel Cln1R151X mouse model of infantile neuronal ceroid lipofuscinosis (INCL) for testing nonsense suppression therapy

    PubMed Central

    Miller, Jake N.; Kovács, Attila D.; Pearce, David A.

    2015-01-01

    The neuronal ceroid lipofuscinoses (NCLs), also known as Batten disease, are a group of autosomal recessive neurodegenerative disorders in children characterized by the progressive onset of seizures, blindness, motor and cognitive decline and premature death. Patients with mutations in CLN1 primarily manifest with infantile NCL (INCL or Haltia-Santavuori disease), which is second only to congenital NCL for its age of onset and devastating progression. CLN1 encodes a lysosomal enzyme, palmitoyl-protein thioesterase 1 (PPT1). Nonsense mutations in CLN1 account for 52.3% of all disease causing alleles in infantile NCL, the most common of which worldwide is the p.R151X mutation. Previously, we have shown how nonsense-mediated decay is involved in the degradation of CLN1 mRNA transcripts containing the p.R151X mutation in human lymphoblast cell lines. We have also shown how the read-through drugs gentamicin and ataluren (PTC124) increase CLN1 (PPT1) enzyme activity. Here, we provide the initial characterization of the novel Cln1R151X mouse model of infantile neuronal ceroid lipofuscinosis that we have generated. This nonsense mutation model recapitulates the molecular, histological and behavioral phenotypes of the human disease. Cln1R151X mice showed a significant decrease in Cln1 mRNA level and PPT1 enzyme activity, accumulation of autofluorescent storage material, astrocytosis and microglial activation in the brain. Behavioral characterization of Cln1R151X mice at 3 and 5 months of age revealed significant motor deficits as measured by the vertical pole and rotarod tests. We also show how the read-through compound ataluren (PTC124) increases PPT1 enzyme activity and protein level in Cln1R151X mice in a proof-of-principle study. PMID:25205113

  10. Studies in neuronal ceroid-lipofuscinosis: heterogeneous nature of neuronal autofluorescent lipopigments.

    PubMed

    Garg, H S; Awasthi, Y C; Srivastava, S K

    1981-01-01

    A method has been developed for the complete extraction and fractionation of the autofluorescent lipopigments present in the neuronal tissue of Batten-Spielmeyer-Vogt (BSV) patient and normal subject, respectively. The fluorescent lipopigments that were about three-fold higher in BSV patient's brain as compared with normal subjects were separated into at least 7 fluorometrically and chromatographically distinct fractions by thin layer chromatography (TLC). Although the fluorescent lipopigments of the brain tissue of BSV patient and normal subject showed identical pattern of separation on TLC, the flourescence spectra of the individual lipopigment fractions from BSV patient was different from those of the corresponding fractions from the normal subject. The ultraviolet spectral studies with individual fluorescent lipopigment fractions indicated the presence of highly unsaturated conjugated chromophore.

  11. Protein Product of CLN6 Gene Responsible for Variant Late-Onset Infantile Neuronal Ceroid Lipofuscinosis Interacts with CRMP-2

    PubMed Central

    Benedict, Jared W.; Getty, Amanda L.; Wishart, Thomas M.; Gillingwater, Thomas H.; Pearce, David A.

    2014-01-01

    Mutations in CLN6 cause variant late-onset neuronal ceroid lipofuscinosis (vLINCL), a childhood neurodegenerative disorder resulting from aberrant neuronal cell loss and pathological accumulation of lysosomal auto-fluorescent storage material in the central nervous system. The direct function of the endoplasmic reticulum– resident protein CLN6 and how dysfunction of this protein results in vLINCL are unknown. We report that CLN6 interacts with collapsin response mediator protein-2 (CRMP-2). To further understand the significance and possible contribution to vLINCL of the CLN6–CRMP-2 interaction, we utilized the nclf mouse, which harbors mutations in CLN6. Significantly, CRMP-2 protein level was found to be reduced in the nclf mouse brain, particularly in the thalamus. Because CRMP-2 functions in growth cone collapse and is an effector protein downstream of Sema3A signaling, this pathway was examined via a dorsal root ganglion (DRG) repulsion assay. However, there were no defects in the repulsion of DRGs derived from nclf mice, indicating that the loss of CLN6 does not affect Sema3A signaling. CRMP-2 has also been implicated in controlling axon number and outgrowth, as observed in cultured hippocampal neurons. Therefore, we explored the formation and maturation of hippocampal neurons derived from nclf mice in a glial coculture system. The maturation of these neurons was reduced; by day in vitro (DIV) 8, more than 50% of nclf-derived hippocampal neurons had died. Additionally, beginning around DIV4, nclf neurons were less mature than their WT counterparts, presumably because of an inability to form mature synaptic connections. We concluded that alterations in neurite maturation resulting from a loss of CLN6–CRMP-2 interaction may contribute to neuronal dysfunction and pathology in vLINCL. PMID:19235893

  12. Tandem Mass Spectrometry Assays of Palmitoyl Protein Thioesterase 1 and Tripeptidyl Peptidase Activity in Dried Blood Spots for the Detection of Neuronal Ceroid Lipofuscinoses in Newborns

    PubMed Central

    2015-01-01

    We report new substrates for quantitative enzyme activity measurements of human palmitoyl protein thioesterase (PPT1) and tripeptidyl peptidase (TPP1) in dried blood spots from newborns using tandem mass spectrometry. Deficiencies in these enzyme activities due to inborn errors of metabolism cause neuronal ceroid lipofuscinoses. The assays use synthetic compounds that were designed to mimic the natural substrates. Incubation produces nanomole quantities of enzymatic products per a blood spot that are quantified by tandem mass spectrometry using synthetic internal standards and selected reaction monitoring. The assays utilize a minimum steps for sample workup and can be run in a duplex format for the detection of neuronal ceroid lipofuscinoses or potentially multiplexed with other mass spectrometry-based assays for newborn screening of lysosomal storage disorders. PMID:25019629

  13. Neuronal ceroid lipofuscinosis type CLN2: A new rationale for the construction of phenotypic subgroups based on a survey of 25 cases in South America

    PubMed Central

    Kohan, Romina; Noelia Carabelos, María; Xin, Winnie; Sims, Katherine; Guelbert, Norberto; Adriana Cismondi, Inés; Pons, Patricia; Alonso, Graciela Irene; Troncoso, Mónica; Witting, Scarlet; Pearce, David A.; de Kremer, Raquel Dodelson; Oller-Ramírez, Ana María; de Halac, Inés Noher

    2013-01-01

    Tripeptidyl-peptidase 1 (TPP1) null or residual activity occurs in neuronal ceroid lipofuscinosis (NCL) with underlying TPP1/CLN2 mutations. A survey of 25 South American CLN2 affected individuals enabled the differentiation of two phenotypes: classical late-infantile and variant juvenile, each in approximately 50% of patients, with residual TPP1 activity occurring in approximately 32%. Each individual was assigned to one of three subgroups: (I) n=11, null TPP1 activity in leukocytes; (II) n=8, residual TPP1 activity of 0.60–15.85 nmol/h/mg (nr 110–476); (III) n=6, activity not measured in leukocytes. Curvilinear bodies (CB) appeared in almost all studied CLN2 subjects; the only exceptions occurred in cases of subgroup II: two individuals had combined CBs/fingerprints (FPs), and one case had pure FPs. There were 15 mutations (4 first published in this paper, 3 previously observed in South America by our group, and 8 previously observed by others). In subgroup I, mutations were either missense or nonsense; in subgroups II and III, mutations prevailed at the non-conserved intronic site, c.887-10A>G (intron 7), and to a lesser extent at c.89+5G>C (intron 2), in heterozygous combinations. Grouping phenotypically and genetically known individuals on the basis of TPP1 activity supported the concept that residual enzyme activity underlies a protracted disease course. The prevalence of intronic mutations at nonconserved sites in subgroup II individuals indicates that some alternative splicing might allow some residual TPP1 activity. PMID:23266810

  14. A canine Arylsulfatase G (ARSG) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis.

    PubMed

    Abitbol, Marie; Thibaud, Jean-Laurent; Olby, Natasha J; Hitte, Christophe; Puech, Jean-Philippe; Maurer, Marie; Pilot-Storck, Fanny; Hédan, Benoit; Dréano, Stéphane; Brahimi, Sandra; Delattre, Delphine; André, Catherine; Gray, Françoise; Delisle, Françoise; Caillaud, Catherine; Bernex, Florence; Panthier, Jean-Jacques; Aubin-Houzelstein, Geneviève; Blot, Stéphane; Tiret, Laurent

    2010-08-17

    Neuronal ceroid lipofuscinoses (NCLs) represent the most common group of inherited progressive encephalopathies in children. They are characterized by progressive loss of vision, mental and motor deterioration, epileptic seizures, and premature death. Rare adult forms of NCL with late onset are known as Kufs' disease. Loci underlying these adult forms remain unknown due to the small number of patients and genetic heterogeneity. Here we confirm that a late-onset form of NCL recessively segregates in US and French pedigrees of American Staffordshire Terrier (AST) dogs. Through combined association, linkage, and haplotype analyses, we mapped the disease locus to a single region of canine chromosome 9. We eventually identified a worldwide breed-specific variant in exon 2 of the Arylsulfatase G (ARSG) gene, which causes a p.R99H substitution in the vicinity of the catalytic domain of the enzyme. In transfected cells or leukocytes from affected dogs, the missense change leads to a 75% decrease in sulfatase activity, providing a functional confirmation that the variant might be the NCL-causing mutation. Our results uncover a protein involved in neuronal homeostasis, identify a family of candidate genes to be screened in patients with Kufs' disease, and suggest that a deficiency in sulfatase is part of the NCL pathogenesis.

  15. Homogeneous PCR nucleobase quenching assays to detect four mutations that cause neuronal ceroid lipofuscinosis: T75P and R151X in CLN1, and IVS5-1G>C and R208X in CLN2.

    PubMed

    Leman, Adam R; Polochock, Susan; Mole, Sara E; Pearce, David A; Rothberg, Paul G

    2006-10-15

    The neuronal ceroid lipofuscinoses (NCLs) are a family of autosomal recessive lysosomal storage diseases characterized by progressive epilepsy, dementia and visual loss. The juvenile form of the disease (onset age 4-8 years with visual loss) is usually caused by mutations in the CLN3 gene, but some cases have been shown to be due to specific mutations in the CLN1 or CLN2 genes, which are usually associated with NCL with onset in infancy or late infancy, respectively. The CLN1 mutations T75P and R151X, and the CLN2 mutations R208X and IVS5-1G>C, are found in many NCL patients with a juvenile presentation that is not due to CLN3 mutation. We have developed and validated a set of assays for these mutations using PCR followed by differential melting of a fluorescently labeled oligo probe, on a Roche LightCycler platform. The nucleobase quenching phenomenon was used to detect probe hybridization. The tests were validated using alternate assays: PCR followed by allele specific restriction enzyme digestion for the CLN1 mutations, and PCR followed by sequencing for the CLN2 mutations. The homogeneous PCR method gave 100% concordance of results with the alternate methods. This new assay, combined with a test for the common 1 kbp deletion in the CLN3 gene, provides a set of DNA-based assays suitable for detection of the most common mutations causing NCL with onset in the juvenile age range.

  16. Melatonin ineffective in neuronal ceroid lipofuscinosis patients with fragmented or normal motor activity rhythms recorded by wrist actigraphy.

    PubMed

    Hätönen, T; Kirveskari, E; Heiskala, H; Sainio, K; Laakso, M L; Santavuori, P

    1999-04-01

    Melatonin was tested as a sleeping pill in five patients with neuronal ceroid lipofuscinoses. The single-blind, placebo-controlled study consisted of motor activity recordings, sleep logs, and administration of placebo or melatonin (2.5 or 5 mg). Daily motor activity rhythms were measured by wrist actigraphy during four 7-day periods (baseline, placebo, melatonin 2.5 mg, and melatonin 5 mg). The placebo or melatonin was administered in the evenings for 3 weeks, and the recordings were made during the last week of the 3-week treatment. Sleep logs were kept by the caregivers during the recordings. Based on period analyses, the activity recordings were evaluated to display a normal (24-h) or fragmented rhythm. Three patients had normal motor activity patterns during the baseline recordings, and administration of placebo or melatonin did not affect their rest/activity rhythms. Two patients had abnormally fragmented activity rhythms during the baseline periods, and administration of placebo or melatonin did not induce synchronization. According to the actigraphic data, there were no changes in activity rhythms resulting from administration of melatonin. However, based on the observations, three families reported that melatonin slightly improved the sleep quality of the patients. These controversial findings show the difficulties involved in specifying the role of melatonin in modulating sleep. Thus, we conclude that more evidence is required before the significance of melatonin as a sleeping pill is defined.

  17. Inefficient cleavage of palmitoyl-protein thioesterase (PPT) substrates by aminothiols: implications for treatment of infantile neuronal ceroid lipofuscinosis.

    PubMed

    Lu, J-Y; Hofmann, S L

    2006-02-01

    Infantile neuronal ceroid lipofuscinosis (INCL, also known as infantile Batten disease) is a devastating neurodegenerative disorder caused by deficiency in the lysosomal enzyme palmitoyl-protein thioesterase (PPT, or CLN1), which functions to remove long-chain fatty acids from cysteine residues in proteins. A previous study suggested that the drug cysteamine, a simple aminothiol used in the treatment of cystinosis, may have utility in the treatment of INCL. In the current study, we compared the catalytic rate constants for the conversion of palmitoyl-CoA (a PPT substrate) and cystine (which accumulates in cystinosis) by cysteamine. We found that while cysteamine can react with palmitoyl-CoA, the rate constant is 10(3)-fold less than the reaction with cystine. Structure-activity studies suggested that it is the thiolate ion that is reactive in the cleavage reaction and that the amino group probably facilitates lysosomal entry. A modest effect of cysteamine (and two related aminothiols, WR 1065 and dimethylaminoethanethiol, DMAET) on PPT substrate accumulation in INCL lymphoblasts was observed. However, at optimum concentration a paradoxical increase in saposin immunoreactivity was seen, indicating possible lysosomal dysfunction. Improvements are needed in the design of small molecules for the treatment of INCL disease.

  18. Increased Expression of the Large Conductance, Calcium-Activated K+ (BK) Channel in Adult-Onset Neuronal Ceroid Lipofuscinosis

    PubMed Central

    Donnelier, Julien; Braun, Samuel T.; Dolzhanskaya, Natalia; Ahrendt, Eva; Braun, Andrew P.; Velinov, Milen; Braun, Janice E. A.

    2015-01-01

    Cysteine string protein (CSPα) is a presynaptic J protein co-chaperone that opposes neurodegeneration. Mutations in CSPα (i.e., Leu115 to Arg substitution or deletion (Δ) of Leu116) cause adult neuronal ceroid lipofuscinosis (ANCL), a dominantly inherited neurodegenerative disease. We have previously demonstrated that CSPα limits the expression of large conductance, calcium-activated K+ (BK) channels in neurons, which may impact synaptic excitability and neurotransmission. Here we show by western blot analysis that expression of the pore-forming BKα subunit is elevated ~2.5 fold in the post-mortem cortex of a 36-year-old patient with the Leu116∆ CSPα mutation. Moreover, we find that the increase in BKα subunit level is selective for ANCL and not a general feature of neurodegenerative conditions. While reduced levels of CSPα are found in some postmortem cortex specimens from Alzheimer’s disease patients, we find no concomitant increase in BKα subunit expression in Alzheimer’s specimens. Both CSPα monomer and oligomer expression are reduced in synaptosomes prepared from ANCL cortex compared with control. In a cultured neuronal cell model, CSPα oligomers are short lived. The results of this study indicate that the Leu116∆ mutation leads to elevated BKα subunit levels in human cortex and extend our initial work in rodent models demonstrating the modulation of BKα subunit levels by the same CSPα mutation. While the precise sequence of pathogenic events still remains to be elucidated, our findings suggest that dysregulation of BK channels may contribute to neurodegeneration in ANCL. PMID:25905915

  19. Oral Cysteamine bitartrate and N-acetylcysteine combination for patients with infantile neuronal ceroid lipofuscinosis:a pilot study

    PubMed Central

    Levin, Sondra W.; Baker, Eva H.; Zein, Wadih M.; Zhang, Zhongjian; Quezado, Zenaide M.N.; Miao, Ning; Gropman, Andrea; Griffin, Kurt J.; Bianconi, Simona; Chandra, Goutam; Khan, Omar I.; Caruso, Rafael C.; Liu, Aiyi; Mukherjee, Anil B.

    2014-01-01

    Summary Background Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating neurodegenerative lysosomal storage disease caused by mutations in the CLN1 gene encoding palmitoyl-protein thioesterase-1 (PPT1). PPT1-deficiency causes lysosomal ceroid accumulation leading to INCL pathogenesis. Previously, we reported that phosphocysteamine and N-acetylcysteine mediated ceroid depletion in cultured cells from INCL patients. We conducted a pilot study to determine whether a combination of cysteamine bitartrate and N-acetylcysteine is beneficial for these patients. Methods Patients (6-month to 3-years old) with any combination of 2 of the 7 most lethal PPT1 mutations were admitted. All patients were recruited from physician referrals and the PPT1 mutations were analyzed prior to admission. Patients were evaluated by electroretinography(ERG), brain MRI and MRS, electroencephalography (EEG), and electron microscopic analyses of leukocytes for granular osmiophilic deposits (GRODs). Patients received oral cysteamine bitartrate (60mg/kg/day) and N-acetylcysteine (60mg/kg/day) and were evaluated every 6 to 12 months until they showed isoelectric EEG attesting to a vegetative state or were too sick to travel. Outcomes were compared with the reported INCL natural history. In two cases, the disease progression was compared with that of a sibling who was above the age limit for inclusion into the protocol. Findings Between March, 2001, and June, 2011, we recruited 10 children with INCL but one was lost to follow-up after the first visit. Thus, a total of 9 patients (5 females and 4 males) were studied. At the first follow-up visit, peripheral leukocytes in all 9 patients showed virtually complete depletion of GRODs and 7 of 9 patients manifested less irritability and/or improved alertness based upon parental and physician observations. Evaluation by Denver scale showed acquisition of no new developmental skills and retinal function assessed by ERG progressively declined

  20. Guidelines for incorporating scientific knowledge and practice on rare diseases into higher education: neuronal ceroid lipofuscinoses as a model disorder.

    PubMed

    Cismondi, Inés Adriana; Kohan, Romina; Adams, Heather; Bond, Mike; Brown, Rachel; Cooper, Jonathan D; de Hidalgo, Perla K; Holthaus, Sophia-Martha Kleine; Mole, Sara E; Mugnaini, Julia; de Ramirez, Ana María Oller; Pesaola, Favio; Rautenberg, Gisela; Platt, Frances M; Noher de Halac, Inés

    2015-10-01

    This article addresses the educational issues associated with rare diseases (RD) and in particular the Neuronal Ceroid Lipofuscinoses (NCLs, or CLN diseases) in the curricula of Health Sciences and Professional's Training Programs. Our aim is to develop guidelines for improving scientific knowledge and practice in higher education and continuous learning programs. Rare diseases (RD) are collectively common in the general population with 1 in 17 people affected by a RD in their lifetime. Inherited defects in genes involved in metabolism are the commonest group of RD with over 8000 known inborn errors of metabolism. The majority of these diseases are neurodegenerative including the NCLs. Any professional training program on NCL must take into account the medical, social and economic burdens related to RDs. To address these challenges and find solutions to them it is necessary that individuals in the government and administrative authorities, academia, teaching hospitals and medical schools, the pharmaceutical industry, investment community and patient advocacy groups all work together to achieve these goals. The logistical issues of including RD lectures in university curricula and in continuing medical education should reflect its complex nature. To evaluate the state of education in the RD field, a summary should be periodically up dated in order to assess the progress achieved in each country that signed up to the international conventions addressing RD issues in society. It is anticipated that auditing current practice will lead to higher standards and provide a framework for those educators involved in establishing RD teaching programs world-wide. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Treatment of the Ppt1−/− Mouse Model of Infantile Neuronal Ceroid Lipofuscinosis with the NMDA Receptor Antagonist Memantine

    PubMed Central

    Finn, Rozzy; Kovács, Attila D.; Pearce, David A.

    2014-01-01

    The neuronal ceroid lipofuscinoses, a family of neurodegenerative lysosomal storage disorders, represent the most common cause of pediatric-onset neurodegeneration. The infantile form has a devastatingly early onset and one of the fastest progressing disease courses. Despite decades of research, the molecular mechanisms driving neuronal loss in infantile neuronal ceroid lipofuscinosis remain unknown. We have previously shown that NMDA-type glutamate receptors in the Ppt1−/− mouse model of this disease exhibit a hyperfunctional phenotype and postulate that aberrant glutamatergic activity may contribute to neural pathology in both the mouse model and human patients. To test this hypothesis, we treated Ppt1−/− mice with the NMDA receptor antagonist memantine and assessed their response to the drug using an accelerating rotarod. At 20 mg/kg, memantine treatment induced a delayed but notable improvement in Ppt1−/− mice. Much remains to be assessed before moving to patient trials, but these results suggest memantine has potential as a treatment. PMID:24014511

  2. Refined assignment of the infantile neuronal ceroid lipofuscinosis (INCL, CLN1) locus at 1p32: Incorporation of linkage disequilibrium in multipoint analysis

    SciTech Connect

    Hellsten, E.; Vesa, J.; Peltonen, L.; Jaervela, I. ); Speer, M.C.; Ott, J. New York State Psychiatric Institute, New York ); Maekelae, T.P.; Alitalo, K. )

    1993-06-01

    Infantile neuronal ceroid lipofuscinosis, INCL, CLN1, is an autosomally inherited progressive neuro-generative disorder. The disease results in the massive death of cortical neurons, suggesting an essential role for the CLN1 gene product in the normal neuronal maturation during the first years of life. Identification of new multiallelic markers has now made possible the construction of a refined genetic map encompassing the CLN1 locus at 1p32. Strong allelic association was detected with a new, highly polymorphic HY-TM1 marker. The authors incorporated this observed linkage disequilibrium into multipoint linkage analysis, which significantly increased the informativeness of the limited family material and facilitated refined assignment of the CLN1 locus. 23 refs., 2 figs., 4 tabs.

  3. Neuronal ceroid lipofuscinosis (NCL) is caused by the entire deletion of CLN8 in the Alpenländische Dachsbracke dog.

    PubMed

    Hirz, M; Drögemüller, M; Schänzer, A; Jagannathan, V; Dietschi, E; Goebel, H H; Hecht, W; Laubner, S; Schmidt, M J; Steffen, F; Hilbe, M; Köhler, K; Drögemüller, C; Herden, C

    2017-03-01

    Neuronal ceroid lipofuscinoses (NCLs) are inherited lysosomal storage diseases that have been described in a variety of dog breeds, where they are caused by different mutations in different genes. However, the causative gene defect in the breed Alpenländische Dachsbracke remained unknown so far. Here we present two confirmed cases of NCL in Alpenländische Dachsbracke dogs from different litters of the same sire with a different dam harboring the same underlying novel mutation in the CLN8 gene. Case 1, a 2-year-old male Alpenländische Dachsbracke was presented with neurological signs including disorientation, character changes including anxiety states and aggressiveness, sudden blindness and reduction of food intake. Magnetic resonance imaging (MRI) scans showed cerebral atrophy with dilation of all cerebral ventricles, thinning of the intermediate mass of the thalamus and widening of the cerebral sulci. Postmortem examination of the central nervous system (CNS) showed neuronal loss in the cerebral cortex, cerebellum and spinal cord with massive intracellular deposits of ceroid pigment. Additional ceroid-lipofuscin deposits were observed in the enteric nervous system and in macrophages within spleen, lymph nodes and lung. Ultrastructural analyses confirmed NCL with the presence of osmiophilic membrane bounded lamellar-like structures. Case 2, a 1,5-year old female Alpenländische Dachsbracke was presented with progressive generalized forebrain disease including mental changes such as fearful reactions to various kinds of external stimuli and disorientation. The dog also displayed seizures, absence of menace reactions and negative cotton-ball test with normal pupillary light reactions. The clinical and post mortem examination yielded similar results in the brain as in Case 1. Whole genome sequencing of Case 1 and PCR results of both cases revealed a homozygous deletion encompassing the entire CLN8 gene as the most likely causative mutation for the NCL form

  4. The neuronal ceroid lipofuscinosis Cln8 gene expression is developmentally regulated in mouse brain and up-regulated in the hippocampal kindling model of epilepsy

    PubMed Central

    Lonka, Liina; Aalto, Antti; Kopra, Outi; Kuronen, Mervi; Kokaia, Zaal; Saarma, Mart; Lehesjoki, Anna-Elina

    2005-01-01

    Background The neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders characterized by accumulation of autofluorescent material in many tissues, especially in neurons. Mutations in the CLN8 gene, encoding an endoplasmic reticulum (ER) transmembrane protein of unknown function, underlie NCL phenotypes in humans and mice. The human phenotype is characterized by epilepsy, progressive psychomotor deterioration and visual loss, while motor neuron degeneration (mnd) mice with a Cln8 mutation show progressive motor neuron dysfunction and retinal degeneration. Results We investigated spatial and temporal expression of Cln8 messenger ribonucleic acid (mRNA) using in situ hybridization, reverse transcriptase polymerase chain reaction (RT-PCR) and northern blotting. Cln8 is ubiquitously expressed at low levels in embryonic and adult tissues. In prenatal embryos Cln8 is most prominently expressed in the developing gastrointestinal tract, dorsal root ganglia (DRG) and brain. In postnatal brain the highest expression is in the cortex and hippocampus. Expression of Cln8 mRNA in the central nervous system (CNS) was also analyzed in the hippocampal electrical kindling model of epilepsy, in which Cln8 expression was rapidly up-regulated in hippocampal pyramidal and granular neurons. Conclusion Expression of Cln8 in the developing and mature brain suggests roles for Cln8 in maturation, differentiation and supporting the survival of different neuronal populations. The relevance of Cln8 up-regulation in hippocampal neurons of kindled mice should be further explored. PMID:15826318

  5. Novel rapid genotyping assays for neuronal ceroid lipofuscinosis in Border Collie dogs and high frequency of the mutant allele in Japan.

    PubMed

    Mizukami, Keijiro; Chang, Hye-Sook; Yabuki, Akira; Kawamichi, Takuji; Kawahara, Natsuko; Hayashi, Daisuke; Hossain, Mohammad A; Rahman, Mohammad M; Uddin, Mohammad M; Yamato, Osamu

    2011-11-01

    Neuronal ceroid lipofuscinosis (NCL) constitutes a group of recessively inherited lysosomal storage diseases that primarily affect neuronal cells. Such diseases share certain clinical and pathologic features in human beings and animals. Neuronal ceroid lipofuscinosis in Border Collie dogs was first detected in Australia in the 1980s, and the pathogenic mutation was shown to be a nonsense mutation (c.619C>T) in exon 4 in canine CLN5 gene. In the present study, novel rapid genotyping assays including polymerase chain reaction (PCR)-restriction fragment length polymorphism, PCR primer-induced restriction analysis, mutagenically separated PCR, and real-time PCR with TaqMan minor groove binder probes, were developed. The utility of microchip electrophoresis was also evaluated. Furthermore, a genotyping survey was carried out in a population of Border Collies in Japan using these assays to determine the current allele frequency in Japan, providing information to control and prevent this disease in the next stage. All assays developed in the current study are available to discriminate these genotypes, and microchip electrophoresis showed a timesaving advantage over agarose gel electrophoresis. Of all assays, real-time PCR was the most suitable for large-scale examination because of its high throughput. The genotyping survey demonstrated that the carrier frequency was 8.1%. This finding suggested that the mutant allele frequency of NCL in Border Collies is high enough in Japan that measures to control and prevent the disease would be warranted. The genotyping assays developed in the present study could contribute to the prevention of NCL in Border Collies.

  6. Apparent loss and hypertrophy of interneurons in a mouse model of neuronal ceroid lipofuscinosis: evidence for partial response to insulin-like growth factor-1 treatment.

    PubMed

    Cooper, J D; Messer, A; Feng, A K; Chua-Couzens, J; Mobley, W C

    1999-04-01

    The neuronal ceroid lipofuscinoses (NCL) are progressive neurodegenerative disorders with onset from infancy to adulthood that are manifested by blindness, seizures, and dementia. In NCL, lysosomes accumulate autofluorescent proteolipid in the brain and other tissues. The mnd/mnd mutant mouse was first characterized as exhibiting adult-onset upper and lower motor neuron degeneration, but closer examination revealed early, widespread pathology similar to that seen in NCL. We used the autofluorescent properties of accumulated storage material to map which CNS neuronal populations in the mnd/mnd mouse show NCL-like pathological changes. Pronounced, early accumulation of autofluorescent lipopigment was found in subpopulations of GABAergic neurons, including interneurons in the cortex and hippocampus. Staining for phenotypic markers normally present in these neurons revealed progressive loss of staining in the cortex and hippocampus of mnd/mnd mice, with pronounced hypertrophy of remaining detectable interneurons. In contrast, even in aged mutant mice, many hippocampal interneurons retained staining for glutamic acid decarboxylase. Treatment with insulin-like growth factor-1 partially restored interneuronal number and reduced hypertrophy in some subregions. These results provide the first evidence for the involvement of interneurons in a mouse model of NCL. Moreover, our findings suggest that at least some populations of these neurons persist in a growth factor-responsive state.

  7. Neuronal ceroid lipofuscinoses (NCL)

    MedlinePlus

    ... NCL include: Abnormally increased muscle tone or spasm Blindness or vision problems Dementia Lack of muscle coordination ... early can have vision problems that progress to blindness and problems with mental function that get worse. ...

  8. Neuronal ceroid lipofuscinosis in Devon cattle is caused by a single base duplication (c.662dupG) in the bovine CLN5 gene.

    PubMed

    Houweling, Peter J; Cavanagh, Julie A L; Palmer, David N; Frugier, Tony; Mitchell, Nadia L; Windsor, Peter A; Raadsma, Herman W; Tammen, Imke

    2006-10-01

    The neuronal ceroid lipofuscinoses (NCLs, Batten disease) are recessively inherited neurodegenerative disorders that affect humans and other animals, characterised by brain atrophy and the accumulation of lysosome derived fluorescent storage bodies in neurons and most other cells. Common clinical signs include blindness, ataxia, dementia, seizures and premature death. The associated genes for six different human forms have been identified (CLN1, CLN2, CLN3, CLN5, CLN6 and CLN8), and three other human forms suggested (CLNs 4, 7 and 9). A form of NCL in Australian Devon cattle is caused by a single base duplication (c.662dupG) in bovine CLN5. This mutation causes a frame-shift and premature termination (p.Arg221GlyfsX6) which is predicted to result in a severely truncated protein, analogous to disease causing mutations in human Finnish late infantile variant NCL (CLN5), and a simple genetic diagnostic test has been developed. The symptoms and disease course in cattle also matches CLN5. Only one initiation site was found in the bovine gene, equivalent to the third of four possible initiation sites in the human gene. As cattle are anatomically and physiologically similar to humans with a human-like central nervous system and easy to maintain and breed, they provide a valuable alternative model for CLN5 studies.

  9. Extraneuronal pathology in a canine model of CLN2 neuronal ceroid lipofuscinosis after intracerebroventricular gene therapy that delays neurological disease progression

    PubMed Central

    Katz, M L; Johnson, G C; Leach, S B; Williamson, B G; Coates, J R; Whiting, R E H; Vansteenkiste, D P; Whitney, M S

    2017-01-01

    CLN2 neuronal ceroid lipofuscinosis is a hereditary lysosomal storage disease with primarily neurological signs that results from mutations in TPP1, which encodes the lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Studies using a canine model for this disorder demonstrated that delivery of TPP1 enzyme to the cerebrospinal fluid (CSF) by intracerebroventricular administration of an AAV-TPP1 vector resulted in substantial delays in the onset and progression of neurological signs and prolongation of life span. We hypothesized that the treatment may not deliver therapeutic levels of this protein to tissues outside the central nervous system that also require TPP1 for normal lysosomal function. To test this hypothesis, dogs treated with CSF administration of AAV-TPP1 were evaluated for the development of non-neuronal pathology. Affected treated dogs exhibited progressive cardiac pathology reflected by elevated plasma cardiac troponin-1, impaired cardiac function and development of histopathological myocardial lesions. Progressive increases in the plasma activity levels of alanine aminotransferase and creatine kinase indicated development of pathology in the liver and muscles. The treatment also did not prevent disease-related accumulation of lysosomal storage bodies in the heart or liver. These studies indicate that optimal treatment outcomes for CLN2 disease may require delivery of TPP1 systemically as well as directly to the central nervous system. PMID:28079862

  10. Extraneuronal pathology in a canine model of CLN2 neuronal ceroid lipofuscinosis after intracerebroventricular gene therapy that delays neurological disease progression.

    PubMed

    Katz, M L; Johnson, G C; Leach, S B; Williamson, B G; Coates, J R; Whiting, R E H; Vansteenkiste, D P; Whitney, M S

    2017-02-02

    CLN2 neuronal ceroid lipofuscinosis is a hereditary lysosomal storage disease with primarily neurological signs that results from mutations in TPP1, which encodes the lysosomal enzyme tripeptidyl peptidase-1 (TPP1). Studies using a canine model for this disorder demonstrated that delivery of TPP1 enzyme to the cerebrospinal fluid (CSF) by intracerebroventricular administration of an AAV-TPP1 vector resulted in substantial delays in the onset and progression of neurological signs and prolongation of life span. We hypothesized that the treatment may not deliver therapeutic levels of this protein to tissues outside the central nervous system that also require TPP1 for normal lysosomal function. To test this hypothesis, dogs treated with CSF administration of AAV-TPP1 were evaluated for the development of non-neuronal pathology. Affected treated dogs exhibited progressive cardiac pathology reflected by elevated plasma cardiac troponin-1, impaired cardiac function and development of histopathological myocardial lesions. Progressive increases in the plasma activity levels of alanine aminotransferase and creatine kinase indicated development of pathology in the liver and muscles. The treatment also did not prevent disease-related accumulation of lysosomal storage bodies in the heart or liver. These studies indicate that optimal treatment outcomes for CLN2 disease may require delivery of TPP1 systemically as well as directly to the central nervous system.Gene Therapy advance online publication, 2 February 2017; doi:10.1038/gt.2017.4.

  11. Altered glutamate receptor function in the cerebellum of the Ppt1−/− mouse, a murine model of infantile neuronal ceroid lipofuscinosis

    PubMed Central

    Finn, Rozzy; Kovács, Attila D.; Pearce, David A.

    2011-01-01

    The neuronal ceroid lipofuscinoses (NCLs) are a family of devastating pediatric neurodegenerative disorders and currently represent the most common form of pediatric-onset neurodegeneration. Infantile NCL (INCL), the most aggressive of these disorders, is caused by mutations in the CLN1 gene that encodes the enzyme palmitoyl protein thioesterase 1 (PPT1). Previous studies have suggested that glutamatergic neurotransmission may be disrupted in INCL, and therefore, the present study investigates glutamate receptor function in the Ppt1−/− mouse model of INCL by comparing the sensitivity of cultured WT and Ppt1−/− cerebellar granule cells to glutamate receptor-mediated toxicity. Ppt1−/− neurons were significantly less sensitive to AMPA receptor-mediated toxicity but markedly more vulnerable to NMDA receptor-mediated cell death. Since glutamate receptor function is primarily regulated by the surface expression level of the receptor, the surface level of AMPA and NMDA receptor subunits in the cerebella of WT and Ppt1−/− mice was also examined. Western blotting of surface cross-linked cerebellar samples showed a significantly lower surface level of the GluR4 AMPA receptor subunit in Ppt1−/− mice, providing a plausible explanation for the decreased vulnerability of Ppt1−/− cerebellar neurons to AMPA receptor-mediated cell death. The surface expression of the NR1, NR2A and NR2B NMDA receptor subunits was similar in the cerebella of WT and Ppt1−/− mice, indicating that there is another mechanism behind the increased sensitivity of Ppt1−/− cerebellar granule cells to NMDA toxicity. Our results indicate an AMPA receptor hypo- and NMDA receptor hyperfunction phenotype in Ppt1−/− neurons and provide new therapeutic targets for INCL. PMID:21971706

  12. Glial fibrillary acidic protein is elevated in the lysosomal storage disease classical late-infantile neuronal ceroid lipofuscinosis, but is not a component of the storage material.

    PubMed

    Xu, Su; Sleat, David E; Jadot, Michel; Lobel, Peter

    2010-05-27

    Classical late-infantile neuronal ceroid lipofuscinosis (LINCL) is a fatal neurodegenerative disease of children caused by mutations in TPP1, the gene encoding the lysosomal protease tripeptidyl peptidase 1. LINCL is characterized by lysosomal accumulation of storage material of which only a single protein component, subunit c of mitochondrial ATP synthase, has been well established to date. Identification of other protein constituents of the storage material could provide useful insights into the pathophysiology of disease and the natural substrates for TPP1. We have therefore initiated a proteomic analysis of storage material in brain from a LINCL mouse model. One protein, GFAP (glial fibrillary acidic protein), was found to be elevated in the LINCL mice compared with normal controls in both isolated storage bodies and a lysosome-enriched subcellular fraction that contains storage material. To determine whether GFAP accumulates within the lysosome in LINCL, we examined its intracellular distribution using subcellular fractionation and morphological methods. These experiments demonstrate that GFAP is not a component of the storage material in LINCL, suggesting that reports of GFAP storage in other NCLs may need to be re-examined. A number of other proteins were elevated in the storage material and/or lysosome-enriched fraction from the LINCL mice, but it remains unclear whether these proteins are true constituents of the storage material or, like GFAP, whether they associate with this material upon purification.

  13. Glial fibrillary acidic protein is elevated in the lysosomal storage disease classical late-infantile neuronal ceroid lipofuscinosis but is not a component of the storage material

    PubMed Central

    XU, Su; SLEAT, David E.; JADOT, Michel; LOBEL, Peter

    2010-01-01

    Classical late neuronal ceroid lipofuscinosis (LINCL) is a fatal neurodegenerative disease of children caused by mutations in TPP1, the gene encoding the lysosomal protease tripeptidyl peptidase 1. LINCL is characterized by lysosomal accumulation of storage material of which only a single protein component, subunit c of mitochondrial ATP synthase, has been well established to date. Identification of other protein constituents of the storage material could provide useful insights into the pathophysiology of disease and the natural substrates for TPP1. We have therefore initiated a proteomic analysis of storage material in brain from a LINCL mouse model. One protein, glial fibrillary acidic protein (GFAP), was found to be elevated in the LINCL mice compared to normal controls in both isolated storage bodies and a lysosome-enriched subcellular fraction that contains storage material. To determine whether GFAP accumulates within the lysosome in LINCL, we examined its intracellular distribution using subcellular fractionation and morphological methods. These experiments demonstrate that GFAP is not a component of the storage material in LINCL, suggesting that reports of GFAP storage in other NCLs may need to be reexamined. A number of other proteins were elevated in the storage material and/or lysosome-enriched fraction from the LINCL mice but it remains unclear whether these proteins are true constituents of the storage material or, like GFAP, if they associate with this material upon purification. PMID:20370715

  14. A genome-side search for CLN2, the gene causing late-infantile neuronal ceroid lipofuscinosis

    SciTech Connect

    Kim, D.; Worster, T.; Boustany, R.M.

    1994-09-01

    The neuronal lipofuscinoses (NCLs) are a group of disorders characterized by cognitive decline, blindness, seizures, and death. Pathologically, it is characterized by accumulation of lipofuscin deposits, generally in easily identifiable `curvilinear bodies`. It is inherited as an autosomal recessive disorder, with the exception of the adult onset form, which may be inherited as an autosomal dominant trait. The loci for the juvenile (CLN3), infantile (CLN1), and very recently, Finnish late-infantile (CLN5) NCLs have been mapped by genetic linkage analysis to chromosome 16p, 1p, and 13q, respectively. The classical late-infantile (LNCL) defect (CLN2) has not yet been mapped. Previous analysis with tightly linked markers excluded CLN2 from the CLN1 and CLN3 regions. We have initiated a genome-wide screen for CLN2, taking advantage of the large collection of highly polymorphic markers that has been developed through the Human Genome Initiative. The high degree of heterozygosity of these markers makes it feasible to carry out successful linkage analysis in small nuclear families, such as found in LNCL. Our current collection of LNCL pedigrees includes 19 U.S. families and 11 Costa Rican families. Simulation studies have shown that we can detect linkage using a subset of 6 LNCL families, a 10 cM sieve, and a lod score criterion of 0.50 for follow-up. A linked region spanned by two markers has over a 95% chance of generating such a lod score, while an unlinked marker has less than a 5% chance of doing so. Follow-up will consist of genotyping the additional families and two additional markers in this region. To date, we have completed typing with 65 markers on chromosomes 1, 2, 9, 13, 16, 18, 19, 20, 21, and 22. The results of this analysis formally exclude about 25% of the human genome as the location of CLN2, including the region of chromosome 13 where CLN5 has been mapped. Updated results will be presented.

  15. Partial genetic suppression of a loss-of-function mutant of the neuronal ceroid lipofuscinosis-associated protease TPP1 in Dictyostelium discoideum.

    PubMed

    Phillips, Jonathan E; Gomer, Richard H

    2015-02-01

    Neuronal ceroid lipofuscinosis (NCL) is the most common childhood-onset neurodegenerative disease. NCL is inevitably fatal, and there is currently no treatment available. Children with NCL show a progressive decline in movement, vision and mental abilities, and an accumulation of autofluorescent deposits in neurons and other cell types. Late-infantile NCL is caused by mutations in the lysosomal protease tripeptidyl peptidase 1 (TPP1). TPP1 cleaves tripeptides from the N-terminus of proteins in vitro, but little is known about the physiological function of TPP1. TPP1 shows wide conservation in vertebrates but it is not found in Drosophila, Caenorhabditis elegans or Saccharomyces cerevisiae. Here, we characterize ddTpp1, a TPP1 ortholog present in the social amoeba Dictyostelium discoideum. Lysates from cells lacking ddTpp1 show a reduced but not abolished ability to cleave a TPP1 substrate, suggesting that other Dictyostelium enzymes can perform this cleavage. ddTpp1 and human TPP1 localize to the lysosome in Dictyostelium, indicating conserved function and trafficking. Cells that lack ddTpp1 show precocious multicellular development and a reduced ability to form spores during development. When cultured in autophagy-stimulating conditions, cells lacking ddTpp1 rapidly decrease in size and are less viable than wild-type cells, suggesting that one function of ddTpp1 could be to limit autophagy. Cells that lack ddTpp1 exhibit strongly impaired development in the presence of the lysosome-perturbing drug chloroquine, and this phenotype can be suppressed through a secondary mutation in the gene that we name suppressor of tpp1(-) A (stpA), which encodes a protein with some similarity to mammalian oxysterol-binding proteins (OSBPs). Taken together, these results suggest that targeting specific proteins could be a viable way to suppress the effects of loss of TPP1 function.

  16. Progressive retinal degeneration and glial activation in the CLN6 (nclf) mouse model of neuronal ceroid lipofuscinosis: a beneficial effect of DHA and curcumin supplementation.

    PubMed

    Mirza, Myriam; Volz, Cornelia; Karlstetter, Marcus; Langiu, Monica; Somogyi, Aleksandra; Ruonala, Mika O; Tamm, Ernst R; Jägle, Herbert; Langmann, Thomas

    2013-01-01

    Neuronal ceroid lipofuscinosis (NCL) is a group of neurodegenerative lysosomal storage disorders characterized by vision loss, mental and motor deficits, and spontaneous seizures. Neuropathological analyses of autopsy material from NCL patients and animal models revealed brain atrophy closely associated with glial activity. Earlier reports also noticed loss of retinal cells and reactive gliosis in some forms of NCL. To study this phenomenon in detail, we analyzed the ocular phenotype of CLN6 (nclf) mice, an established mouse model for variant-late infantile NCL. Retinal morphometry, immunohistochemistry, optokinetic tracking, electroretinography, and mRNA expression were used to characterize retinal morphology and function as well as the responses of Müller cells and microglia. Our histological data showed a severe and progressive degeneration in the CLN6 (nclf) retina co-inciding with reactive Müller glia. Furthermore, a prominent phenotypic transformation of ramified microglia to phagocytic, bloated, and mislocalized microglial cells was identified in CLN6 (nclf) retinas. These events overlapped with a rapid loss of visual perception and retinal function. Based on the strong microglia reactivity we hypothesized that dietary supplementation with immuno-regulatory compounds, curcumin and docosahexaenoic acid (DHA), could ameliorate microgliosis and reduce retinal degeneration. Our analyses showed that treatment of three-week-old CLN6 (nclf) mice with either 5% DHA or 0.6% curcumin for 30 weeks resulted in a reduced number of amoeboid reactive microglia and partially improved retinal function. DHA-treatment also improved the morphology of CLN6 (nclf) retinas with a preserved thickness of the photoreceptor layer in most regions of the retina. Our results suggest that microglial reactivity closely accompanies disease progression in the CLN6 (nclf) retina and both processes can be attenuated with dietary supplemented immuno-modulating compounds.

  17. Progressive Retinal Degeneration and Glial Activation in the CLN6nclf Mouse Model of Neuronal Ceroid Lipofuscinosis: A Beneficial Effect of DHA and Curcumin Supplementation

    PubMed Central

    Mirza, Myriam; Volz, Cornelia; Karlstetter, Marcus; Langiu, Monica; Somogyi, Aleksandra; Ruonala, Mika O.; Tamm, Ernst R.

    2013-01-01

    Neuronal ceroid lipofuscinosis (NCL) is a group of neurodegenerative lysosomal storage disorders characterized by vision loss, mental and motor deficits, and spontaneous seizures. Neuropathological analyses of autopsy material from NCL patients and animal models revealed brain atrophy closely associated with glial activity. Earlier reports also noticed loss of retinal cells and reactive gliosis in some forms of NCL. To study this phenomenon in detail, we analyzed the ocular phenotype of CLN6nclf mice, an established mouse model for variant-late infantile NCL. Retinal morphometry, immunohistochemistry, optokinetic tracking, electroretinography, and mRNA expression were used to characterize retinal morphology and function as well as the responses of Müller cells and microglia. Our histological data showed a severe and progressive degeneration in the CLN6nclf retina co-inciding with reactive Müller glia. Furthermore, a prominent phenotypic transformation of ramified microglia to phagocytic, bloated, and mislocalized microglial cells was identified in CLN6nclf retinas. These events overlapped with a rapid loss of visual perception and retinal function. Based on the strong microglia reactivity we hypothesized that dietary supplementation with immuno-regulatory compounds, curcumin and docosahexaenoic acid (DHA), could ameliorate microgliosis and reduce retinal degeneration. Our analyses showed that treatment of three-week-old CLN6nclf mice with either 5% DHA or 0.6% curcumin for 30 weeks resulted in a reduced number of amoeboid reactive microglia and partially improved retinal function. DHA-treatment also improved the morphology of CLN6nclf retinas with a preserved thickness of the photoreceptor layer in most regions of the retina. Our results suggest that microglial reactivity closely accompanies disease progression in the CLN6nclf retina and both processes can be attenuated with dietary supplemented immuno-modulating compounds. PMID:24124525

  18. A CLN8 nonsense mutation in the whole genome sequence of a mixed breed dog with neuronal ceroid lipofuscinosis and Australian Shepherd ancestry.

    PubMed

    Guo, Juyuan; Johnson, Gary S; Brown, Holly A; Provencher, Michele L; da Costa, Ronaldo C; Mhlanga-Mutangadura, Tendai; Taylor, Jeremy F; Schnabel, Robert D; O'Brien, Dennis P; Katz, Martin L

    2014-08-01

    The neuronal ceroid lipofuscinoses (NCLs) are hereditary neurodegenerative diseases characterized by seizures and progressive cognitive decline, motor impairment, and vision loss accompanied by accumulation of autofluorescent lysosomal storage bodies in the central nervous system and elsewhere in the body. Mutations in at least 14 genes underlie the various forms of NCL. One of these genes, CLN8, encodes an intrinsic membrane protein of unknown function that appears to be localized primarily to the endoplasmic reticulum. Most CLN8 mutations in people result in a form of NCL with a late infantile onset and relatively rapid progression. A mixed breed dog with Australian Shepherd and Blue Heeler ancestry developed neurological signs characteristic of NCL starting at about 8months of age. The signs became progressively worse and the dog was euthanized at 21months of age due to seizures of increasing frequency and severity. Postmortem examination of the brain and retinas identified massive accumulations of intracellular autofluorescent inclusions characteristic of the NCLs. Whole genome sequencing of DNA from this dog identified a CLN8:c.585G>A transition that predicts a CLN8:p.Trp195* nonsense mutation. This mutation appears to be rare in both ancestral breeds. All of our 133 archived DNA samples from Blue Heelers, and 1481 of our 1488 archived Australian Shepherd DNA samples tested homozygous for the reference CLN8:c.585G allele. Four of the Australian Shepherd samples tested heterozygous and 3 tested homozygous for the mutant CLN8:c.585A allele. All 3 dogs homozygous for the A allele exhibited clinical signs of NCL and in 2 of them NCL was confirmed by postmortem evaluation of brain tissue. The occurrence of confirmed NCL in 3 of 4 CLN8:c.585A homozygous dogs, plus the occurrence of clinical signs consistent with NCL in the fourth homozygote strongly suggests that this rare truncating mutation causes NCL. Identification of this NCL-causing mutation provides the

  19. Association between CLN3 (Neuronal Ceroid Lipofuscinosis, CLN3 Type) Gene Expression and Clinical Characteristics of Breast Cancer Patients.

    PubMed

    Makoukji, Joelle; Raad, Mohamad; Genadry, Katia; El-Sitt, Sally; Makhoul, Nadine J; Saad Aldin, Ehab; Nohra, Eden; Jabbour, Mark; Sangaralingam, Ajanthah; Chelala, Claude; Habib, Robert H; Boulos, Fouad; Tfayli, Arafat; Boustany, Rose-Mary

    2015-01-01

    Breast cancer is the most common cancer in women worldwide. Elucidation of underlying biology and molecular pathways is necessary for improving therapeutic options and clinical outcomes. CLN3 protein (CLN3p), deficient in neurodegenerative CLN3 disease is anti-apoptotic, and defects in the CLN3 gene cause accelerated apoptosis of neurons in CLN3 disease and up-regulation of ceramide. Dysregulated apoptotic pathways are often implicated in the development of the oncogenic phenotype. Predictably, CLN3 mRNA expression and CLN3 protein were up-regulated in a number of human and murine breast cancer-cell lines. Here, we determine CLN3 expression in non-tumor vs. tumor samples from fresh and formalin-fixed/paraffin-embedded (FFPE) breast tissue and analyze the association between CLN3 overexpression and different clinicopathological characteristics of breast cancer patients. Additionally, gene expression of 28 enzymes involved in sphingolipid metabolism was determined. CLN3 mRNA is overexpressed in tumor vs. non-tumor breast tissue from FFPE and fresh samples, as well as in mouse MCF7 breast cancer compared to MCF10A normal cells. Of the clinicopathological characteristics of tumor grade, age, menopause status, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), only absence of HER2 expression correlated with CLN3 overexpression. Sphingolipid genes for ceramide synthases 2 and 6 (CerS2; CerS6), delta(4)-desaturase sphingolipid 2 (DEGS2), and acidic sphingomyelinase (SMPD1) displayed higher expression levels in breast cancer vs. control tissue, whereas ceramide galactosyltransferase (UGT8) was underexpressed in breast cancer samples. CLN3 may be a novel molecular target for cancer drug discovery with the goal of modulation of ceramide pathways.

  20. Association between CLN3 (Neuronal Ceroid Lipofuscinosis, CLN3 Type) Gene Expression and Clinical Characteristics of Breast Cancer Patients

    PubMed Central

    Makoukji, Joelle; Raad, Mohamad; Genadry, Katia; El-Sitt, Sally; Makhoul, Nadine J.; Saad Aldin, Ehab; Nohra, Eden; Jabbour, Mark; Sangaralingam, Ajanthah; Chelala, Claude; Habib, Robert H.; Boulos, Fouad; Tfayli, Arafat; Boustany, Rose-Mary

    2015-01-01

    Breast cancer is the most common cancer in women worldwide. Elucidation of underlying biology and molecular pathways is necessary for improving therapeutic options and clinical outcomes. CLN3 protein (CLN3p), deficient in neurodegenerative CLN3 disease is anti-apoptotic, and defects in the CLN3 gene cause accelerated apoptosis of neurons in CLN3 disease and up-regulation of ceramide. Dysregulated apoptotic pathways are often implicated in the development of the oncogenic phenotype. Predictably, CLN3 mRNA expression and CLN3 protein were up-regulated in a number of human and murine breast cancer-cell lines. Here, we determine CLN3 expression in non-tumor vs. tumor samples from fresh and formalin-fixed/paraffin-embedded (FFPE) breast tissue and analyze the association between CLN3 overexpression and different clinicopathological characteristics of breast cancer patients. Additionally, gene expression of 28 enzymes involved in sphingolipid metabolism was determined. CLN3 mRNA is overexpressed in tumor vs. non-tumor breast tissue from FFPE and fresh samples, as well as in mouse MCF7 breast cancer compared to MCF10A normal cells. Of the clinicopathological characteristics of tumor grade, age, menopause status, estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), only absence of HER2 expression correlated with CLN3 overexpression. Sphingolipid genes for ceramide synthases 2 and 6 (CerS2; CerS6), delta(4)-desaturase sphingolipid 2 (DEGS2), and acidic sphingomyelinase (SMPD1) displayed higher expression levels in breast cancer vs. control tissue, whereas ceramide galactosyltransferase (UGT8) was underexpressed in breast cancer samples. CLN3 may be a novel molecular target for cancer drug discovery with the goal of modulation of ceramide pathways. PMID:26528430

  1. Immunosuppression alters disease severity in juvenile Batten disease mice

    PubMed Central

    Seehafer, Sabrina S.; Ramirez-Montealegre, Denia; Wong, Andrew MS; Chan, Chun-Hung; Castaneda, Julian; Horak, Michael; Ahmadi, Sarah M; Lim, Ming J; Cooper, Jonathan D; Pearce, David A

    2011-01-01

    Autoantibodies to brain proteins are present in Juvenile Neuronal Ceroid Lipofuscinosis (Batten disease) patients and the Cln3−/− mouse model of this disease, suggesting an autoimmune component to pathogenesis. Using genetic or pharmaceutical approaches to attenuate this immune response in Cln3−/− mice, we demonstrate decreased neuroinflammation, decreased deposition of Immunoglobulin G in the brain and protection of vulnerable neuron populations. Moreover, immune suppression results in a significant improvement in motor performance providing for the first plausible therapeutic approach for juvenile Batten disease. PMID:20937531

  2. Ceroid in fish

    USGS Publications Warehouse

    Wood, E.M.; Yasutake, W.T.

    1956-01-01

    Since the original description of ceroid in rats, many papers have appeared on the etiology and characteristics of this pigment. It was first seen as a yellow, granular pigment in hematoxylin and eosin sections of the cirrhotic livers of choline deficient rats. The pigment was more fully characterized by Endicott and Lillie, and additional stainging reactions were summarized recently by Lillie. The pigment is sudanophilic in paraffin sections, acid-fast, basophilic, isotropic, iron negative, and highly resistant to solution in water, alcohol, fat solvents, and dilute aqueous acids and alkalis. It is stained by Mallory's hemofuscin stain and Weigert's myelin stain. It reduces osmium tetraoxide and diamine silver carbonate but not ferric ferricyanide. The Gmelin reactions for bile pigments is negative. It has a greenish yellow fluorescence at 3650-3660 Å. It is Schiff positive with or without antecedent diastase digestion after performic or periodic acid oxidation.

  3. Genistein excitation of gonadotrophin-releasing hormone neurones in juvenile female mice.

    PubMed

    Bhattarai, J P; Abrahám, I M; Han, S K

    2013-05-01

    We investigated the effects of the phytoestrogen genistein on gonadotrophin-releasing hormone (GnRH) neurones using single-cell electrophysiology on GnRH-green fluorescent protein (GFP) transgenic juvenile female mice. Perforated patch-clamp recordings from GnRH-GFP neurones showed that approximately 83% of GnRH neurones responded to 30 μm genistein with a markedly prolonged membrane depolarisation. This effect not only persisted in the presence of tetrodotoxin, but also in the presence of amino acid receptor antagonists, indicating the direct site of action on postsynaptic GnRH neurones. Using a voltage clamp technique, we found that 30 μm genistein increased the frequency of synaptic current of GnRH neurones clamped at -60 mV in the presence of glutamate receptor blocker but not GABAA receptor blocker. Pre-incubation of GnRH neurones with 30 μm genistein enhanced kisspeptin-induced membrane depolarisation and firing. GnRH neurones of juvenile mice injected with genistein in vivo showed an enhanced kisspeptin response compared to vehicle-injected controls. The transient receptor potential channel (TRPC) blocker 2-aminoethoxydiphenyl borate (75 μm) blocked the genistein-mediated response on GnRH neurones. These results demonstrate that genistein acts on GnRH neurones in juvenile female mice to induce excitation via GABA neurotransmission and TRPCs to enhance kisspeptin-induced activation. © 2013 British Society for Neuroendocrinology.

  4. Utility of whole exome sequencing in evaluation of juvenile motor neuron disease.

    PubMed

    Agarwal, Sonika; Potocki, Lorraine; Collier, Talia R; Woodbury, Suzanne L; Adesina, Adekunle M; Jones, Jeremy; Lotze, Timothy E

    2016-04-01

    This case report focuses on identifying novel mutations in juvenile motor neuron disease and emphasizes the significance of whole exome sequencing (WES). We report a 13-year-old Hispanic boy with rapidly progressive weakness, muscle atrophy, tremor, and tongue fasciculation, along with upper motor neuron findings of hyperactive gag reflex, hyperreflexia, and cog-wheel rigidity. Electromyography was suggestive of motor neuron disease. After an extensive evaluation, WES was performed. WES identified a heterozygous de novo variant of unknown clinical significance (VUS) in the fused-in-sarcoma gene (FUS) [c.1554_1557del]. Although initially reported as a VUS, the clinical data from our patient and data from the medical literature support that the variant is indeed disease-causing. The genetic etiology of amyotrophic lateral sclerosis (ALS) is heterogeneous and, as clinical sequencing for FUS was not available, WES was the only method by which a diagnosis of juvenile ALS could be made. © 2016 Wiley Periodicals, Inc.

  5. Activation of Strychnine-Sensitive Glycine Receptors by Shilajit on Preoptic Hypothalamic Neurons of Juvenile Mice.

    PubMed

    Bhattarai, Janardhan Prasad; Cho, Dong Hyu; Han, Seong Kyu

    2016-02-29

    Shilajit, a mineral pitch, has been used in Ayurveda and Siddha system of medicine to treat many human ailments, and is reported to contain at least 85 minerals in ionic form. This study examined the possible mechanism of Shilajit action on preoptic hypothalamic neurons using juvenile mice. The hypothalamic neurons are the key regulator of many hormonal systems. In voltage clamp mode at a holding potential of -60 mV, and under a high chloride pipette solution, Shilajit induced dose-dependent inward current. Shilajit-induced inward currents were reproducible and persisted in the presence of 0.5 μM tetrodotoxin (TTX) suggesting a postsynaptic action of Shilajit on hypothalamic neurons. The currents induced by Shilajit were almost completely blocked by 2 μM strychnine (Stry), a glycine receptor antagonist. In addition, Shilajit-induced inward currents were partially blocked by bicuculline. Under a gramicidin-perforated patch clamp mode, Shilajit induced membrane depolarization on juvenile neurons. These results show that Shilajit affects hypothalamic neuronal activities by activating the Stry-sensitive glycine receptor with α₂/α₂β subunit. Taken together, these results suggest that Shilajit contains some ingredients with possible glycine mimetic activities and might influence hypothalamic neurophysiology through activation of Stry-sensitive glycine receptor-mediated responses on hypothalamic neurons postsynaptically.

  6. The equine enteric nervous system--neuron characterization and distribution in adults and juveniles.

    PubMed

    Doxey, D L; Pearson, G T; Milne, E M; Gilmour, J S; Chisholm, H K

    1995-01-01

    A study of myenteric and submucosal plexuses was undertaken in the jejunum and ileum of horses and ponies in which no clinical or pathological evidence of intestinal abnormality was apparent. Complete transverse sections of the intestine, stained by a modified haematoxylin and eosin method, were examined using up to 20 sequential sections per animal. Information was gathered from adult, juvenile and fetal equidae. In adults, the longitudinal muscle layers were thinner than the circular muscle layers and the ileum had thicker layers compared to the jejunum. In adults, the submucosal plexus had more neurons per section than the myenteric plexus by mean ratios of 1:3 in the jejunum and 1:1.9 in the ileum. In juveniles, the ratios were respectively 1:1.8 and 1:1.5 and in the fetus 1:2.5 and 1:1.3. The three-dimensional distribution of neurons in both plexuses varied from animal to animal and no consistent pattern was observed. Groups of neurons contained between one and 42 cells per section examined and their length in a cranio-caudal direction varied from 10 to over 100 microns. There were few statistical differences observed between the cranial, middle and caudal portions of either the jejunum or the ileum when neuron groups or neuron numbers per section were examined in 10 adult animals.

  7. Quantification of Ceroid and Lipofuscin in Skeletal Muscle

    PubMed Central

    Tohma, Hatice; Hepworth, Anna R.; Shavlakadze, Thea; Grounds, Miranda D.; Arthur, Peter G.

    2011-01-01

    Ceroid and lipofuscin are autofluorescent granules thought to be generated as a consequence of chronic oxidative stress. Because ceroid and lipofuscin are persistent in tissue, their measurement can provide a lifetime history of exposure to chronic oxidative stress. Although ceroid and lipofuscin can be measured by quantification of autofluorescent granules, current methods rely on subjective assessment. Furthermore, there has not been any evaluation of variables affecting quantitative measurements. The article describes a simple statistical approach that can be readily applied to quantitate ceroid and lipofuscin. Furthermore, it is shown that several factors, including magnification tissue thickness and tissue level, can affect precision and sensitivity. After optimizing for these factors, the authors show that ceroid and lipofuscin can be measured reproducibly in the skeletal muscle of dystrophic mice (ceroid) and aged mice (lipofuscin). PMID:21804079

  8. Juvenile-onset motor neuron disease caused by novel mutations in β-hexosaminidase

    PubMed Central

    Pierson, Tyler Mark; Torres, Paola A.; Zeng, Bei-Jin; Glanzman, Allan M.; Adams, David; Finkel, Richard S.; Mahuran, Don J.; Pastores, Gregory M.; Tennekoon, Gihan I.; Kolodny, Edwin H.

    2013-01-01

    A 12 year-old female presented with a seven-year history of progressive muscle weakness, atrophy, tremor and fasciculations. Cognition was normal. Rectal biopsy revealed intracellular storage material and biochemical testing indicated low hexosaminidase activity consistent with juvenile-onset GM2-gangliosidosis. Genetic evaluation revealed compound heterozygosity with two novel mutations in the hexosaminidase β-subunit (c.512-3 C>A and c.1613+15_1613+18dup). Protein analysis was consistent with biochemical findings and indicated only a small portion of β-subunits were properly processed. These results provide additional insight into juvenile-onset GM2-gangliosidoses and further expand the number of β-hexosaminidase mutations associated with motor neuron disease. PMID:23158871

  9. Genetic heterogeneity in juvenile NCL

    SciTech Connect

    Hart, Y.M.; Andermann, E.; Mitchison, H.M.

    1994-09-01

    The neuronal ceroid lipofuscinoses (NCL) are a group of related lysosomal storage diseases classified according to the age of onset, clinical syndrome, and pathology. The clinical syndromes include myoclonus, visual failure, progressive dementia, ataxia and generalized tonic clonic seizures in varying combinations depending on the age of onset and pathology. The mode of inheritance is autosomal recessive in most cases, except for several families with the adult form (Kufs` disease) which have autosomal dominant inheritance. Linkage for the infantile (Halatia-Santavuori) form (CLN1), characterized ultrastructurally by lysosomal granular osmiophilic deposits (GROD), has been demonstrated with markers on chromosome lp, while the gene for the typical juvenile (Spielmeyer-Vogt) form (CLN3), characterized by fingerprint-profile inclusions, has been linked to chromosome 16p. The gene locations of the late infantile (Jansky-Bielschowsky) and adult (Kufs` disease) forms are unknown, although it has recently been shown that the late infantile form does not link to chromosome 16p. We describe three siblings, including a pair of monozygotic twins, with juvenile onset NCL with GROD in whom linkage to the CLN3 region of chromsome 16p has been excluded. This would suggest that there is genetic heterogeneity not only among the different clinical syndromes, but also among identical clinical syndromes with different ultrastructural characteristics. Preliminary studies of linkage to chromosome 1p employing the microsatellite marker HY-TM1 have been uninformative. Further studies with other chromosome 1 markers are underway.

  10. Aberrant neuronal avalanches in cortical tissue removed from juvenile epilepsy patients.

    PubMed

    Hobbs, Jon P; Smith, Jodi L; Beggs, John M

    2010-12-01

    Some forms of epilepsy may arise as a result of pathologic interactions among neurons. Many forms of collective activity have been identified, including waves, spirals, oscillations, synchrony, and neuronal avalanches. All these emergent activity patterns have been hypothesized to show pathologic signatures associated with epilepsy. Here, the authors used 60-channel multielectrode arrays to record neuronal avalanches in cortical tissue removed from juvenile epilepsy patients. For comparison, they also recorded activity in rat cortical slices. The authors found that some human tissue removed from epilepsy patients exhibited prolonged periods of hyperactivity not seen in rat slices. In addition, they found a positive correlation between the branching parameter, a measure of network gain, and firing rate in human slices during periods of hyperactivity. This relationship was not present in rat slices. The authors suggest that this positive correlation between the branching parameter and the firing rate is part of a positive feedback loop and may contribute to some forms of epilepsy. These results also indicate that neuronal avalanches are abnormally regulated in slices removed from pediatric epilepsy patients.

  11. Cytoarchitectural impairments in the medium spiny neurons of the Nucleus Accumbens core of hyperactive juvenile rats.

    PubMed

    González-Burgos, I; García-Martínez, S; Velázquez-Zamora, D A; Ponce-Rolón, R

    2010-10-01

    Dopaminergic activity in the Nucleus Accumbens has been strongly implicated in the motor hyperactivity associated with Attention deficit hyperactivity disorder. Dopaminergic and glutamatergic terminals converge on the dendritic spines of medium spiny neurons of the nucleus accumbens core, which modulate the excitatory glutamatergic activity. In this work, a Golgi study was carried out to investigate the effects of dopamine depletion on the cytoarchitecture of dendritic spines of nucleus accumbens core medium spiny neurons. The dopaminergic system of newborn male rats was lesioned intracisternally by using 6-hydroxydopamine, and subsequently, the motor activity, spine density, and the proportion of thin, stubby, mushroom, wide, branched, and double spines was compared to those in control and intact animals. Motor activity was significantly increased in the dopamine-depleted animals and while the spine density was reduced, there was no change in the proportion of the specific types of spines. Larger thin spines were observed in the dopamine-depleted animals. Indeed, dopamine depletion may lead to spine retraction due to the disregulation of spine development, and/or an increase in glutamatergic activity. The enlargement of thin spines may suggest a compensatory mechanism to increase the efficiency of synaptic inputs in response to a decrease in spines number. Together, the present findings suggest an alteration to the excitatory/inhibitory balance on dendritic spines of medium spiny neurons of the nucleus accumbens core in hyperactive juvenile rats following early dopamine depletion.

  12. Intravenous AAV9 efficiently transduces myenteric neurons in neonate and juvenile mice

    PubMed Central

    Gombash, Sara E.; Cowley, Christopher J.; Fitzgerald, Julie A.; Hall, Jodie C. E.; Mueller, Christian; Christofi, Fedias L.; Foust, Kevin D.

    2014-01-01

    Gene therapies for neurological diseases with autonomic or gastrointestinal involvement may require global gene expression. Gastrointestinal complications are often associated with Parkinson's disease and autism. Lewy bodies, a pathological hallmark of Parkinson's brains, are routinely identified in the neurons of the enteric nervous system (ENS) following colon biopsies from patients. The ENS is the intrinsic nervous system of the gut, and is responsible for coordinating the secretory and motor functions of the gastrointestinal tract. ENS dysfunction can cause severe patient discomfort, malnourishment, or even death as in intestinal pseudo-obstruction (Ogilvie syndrome). Importantly, ENS transduction following systemic vector administration has not been thoroughly evaluated. Here we show that systemic injection of AAV9 into neonate or juvenile mice results in transduction of 25–57% of ENS myenteric neurons. Transgene expression was prominent in choline acetyltransferase positive cells, but not within vasoactive intestinal peptide or neuronal nitric oxide synthase cells, suggesting a bias for cells involved in excitatory signaling. AAV9 transduction in enteric glia is very low compared to CNS astrocytes. Enteric glial transduction was enhanced by using a glial specific promoter. Furthermore, we show that AAV8 results in comparable transduction in neonatal mice to AAV9 though AAV1, 5, and 6 are less efficient. These data demonstrate that systemic AAV9 has high affinity for peripheral neural tissue and is useful for future therapeutic development and basic studies of the ENS. PMID:25360081

  13. Intravenous AAV9 efficiently transduces myenteric neurons in neonate and juvenile mice.

    PubMed

    Gombash, Sara E; Cowley, Christopher J; Fitzgerald, Julie A; Hall, Jodie C E; Mueller, Christian; Christofi, Fedias L; Foust, Kevin D

    2014-01-01

    Gene therapies for neurological diseases with autonomic or gastrointestinal involvement may require global gene expression. Gastrointestinal complications are often associated with Parkinson's disease and autism. Lewy bodies, a pathological hallmark of Parkinson's brains, are routinely identified in the neurons of the enteric nervous system (ENS) following colon biopsies from patients. The ENS is the intrinsic nervous system of the gut, and is responsible for coordinating the secretory and motor functions of the gastrointestinal tract. ENS dysfunction can cause severe patient discomfort, malnourishment, or even death as in intestinal pseudo-obstruction (Ogilvie syndrome). Importantly, ENS transduction following systemic vector administration has not been thoroughly evaluated. Here we show that systemic injection of AAV9 into neonate or juvenile mice results in transduction of 25-57% of ENS myenteric neurons. Transgene expression was prominent in choline acetyltransferase positive cells, but not within vasoactive intestinal peptide or neuronal nitric oxide synthase cells, suggesting a bias for cells involved in excitatory signaling. AAV9 transduction in enteric glia is very low compared to CNS astrocytes. Enteric glial transduction was enhanced by using a glial specific promoter. Furthermore, we show that AAV8 results in comparable transduction in neonatal mice to AAV9 though AAV1, 5, and 6 are less efficient. These data demonstrate that systemic AAV9 has high affinity for peripheral neural tissue and is useful for future therapeutic development and basic studies of the ENS.

  14. Methylphenidate Causes Behavioral Impairments and Neuron and Astrocyte Loss in the Hippocampus of Juvenile Rats.

    PubMed

    Schmitz, Felipe; Pierozan, Paula; Rodrigues, André F; Biasibetti, Helena; Grunevald, Matheus; Pettenuzzo, Letícia F; Scaini, Giselli; Streck, Emilio L; Netto, Carlos A; Wyse, Angela T S

    2017-08-01

    Although the use, and misuse, of methylphenidate is increasing in childhood and adolescence, there is little information about the consequences of this psychostimulant chronic use on brain and behavior during development. The aim of the present study was to investigate hippocampus biochemical, histochemical, and behavioral effects of chronic methylphenidate treatment to juvenile rats. Wistar rats received intraperitoneal injections of methylphenidate (2.0 mg/kg) or an equivalent volume of 0.9 % saline solution (controls), once a day, from the 15th to the 45th day of age. Results showed that chronic methylphenidate administration caused loss of astrocytes and neurons in the hippocampus of juvenile rats. BDNF and pTrkB immunocontents and NGF levels were decreased, while TNF-α and IL-6 levels, Iba-1 and caspase 3 cleaved immunocontents (microglia marker and active apoptosis marker, respectively) were increased. ERK and PKCaMII signaling pathways, but not Akt and GSK-3β, were decreased. SNAP-25 was decreased after methylphenidate treatment, while GAP-43 and synaptophysin were not altered. Both exploratory activity and object recognition memory were impaired by methylphenidate. These findings provide additional evidence that early-life exposure to methylphenidate can have complex effects, as well as provide new basis for understanding of the biochemical and behavioral consequences associated with chronic use of methylphenidate during central nervous system development.

  15. Hematopoietic cell transplantation in fetal lambs with ceroid-lipofuscinosis.

    PubMed

    Westlake, V J; Jolly, R D; Jones, B R; Mellor, D J; Machon, R; Zanjani, E D; Krivit, W

    1995-06-05

    Hematopoietic cells from the liver of normal 45-48-day-old fetal lambs (Hb type AA) were transplanted intraperitoneally into 58-60-day-old recipient fetuses (Hb type BB). The recipient fetuses resulted from mating homozygous ceroid-lipofuscinosis affected males with heterozygous, phenotypically normal, females. The sex of the donor fetus was also recorded. At age 2 1/2 months the recipient lambs with ceroid-lipofuscinosis were diagnosed by histopathology of brain biopsies. Monitoring of blood and bone marrow cells showed that an average of 9% of blood cells in ceroid-lipofuscinosis affected recipients were of donor origin. No differences were evident in the clinical course of disease, brain weight, or histopathology of organs between transplanted and non-transplanted lambs with ceroid-lipofuscinosis. Under the conditions of this experiment, transplantation of fetal hematopoietic cells was not beneficial.

  16. Neuropeptide and calcium-binding protein gene expression profiles predict neuronal anatomical type in the juvenile rat

    PubMed Central

    Toledo-Rodriguez, Maria; Goodman, Philip; Illic, Milena; Wu, Caizhi; Markram, Henry

    2005-01-01

    Neocortical neurones can be classified according to several independent criteria: morphological, physiological, and molecular expression (neuropeptides (NPs) and/or calcium-binding proteins (CaBPs)). While it has been suggested that particular NPs and CaBPs characterize certain anatomical subtypes of neurones, there is also considerable overlap in their expression, and little is known about simultaneous expression of multiple NPs and CaBPs in morphologically characterized neocortical neurones. Here we determined the gene expression profiles of calbindin (CB), parvalbumin (PV), calretinin (CR), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), somatostatin (SOM) and cholecystokinin (CCK) in 268 morphologically identified neurones located in layers 2–6 in the juvenile rat somatosensory neocortex. We used patch-clamp electrodes to label neurones with biocytin and harvest the cytoplasm to perform single-cell RT-multiplex PCR. Quality threshold clustering, an unsupervised algorithm that clustered neurones according to their entire profile of expressed genes, revealed seven distinct clusters. Surprisingly, each cluster preferentially contained one anatomical class. Artificial neural networks using softmax regression predicted anatomical types at nearly optimal statistical levels. Classification tree-splitting (CART), a simple binary neuropeptide decision tree algorithm, revealed the manner in which expression of the multiple mRNAs relates to different anatomical classes. Pruning the CART tree revealed the key predictors of anatomical class (in order of importance: SOM, PV, VIP, and NPY). We reveal here, for the first time, a strong relationship between specific combinations of NP and CaBP gene expressions and the anatomical class of neocortical neurones. PMID:15946970

  17. Neuronal intranuclear inclusion disease: two cases of dopa-responsive juvenile parkinsonism with drug-induced dyskinesia.

    PubMed

    Lai, Szu-Chia; Jung, Shih-Ming; Grattan-Smith, Padraic; Sugo, Ella; Lin, Yen-Wen; Chen, Rou-Shayn; Chen, Chiung-Chu; Wu-Chou, Yah-Huei; Lang, Anthony E; Lu, Chin-Song

    2010-07-15

    There are very few conditions that present with dopa-responsive juvenile parkinsonism. We present two such children with neuronal intranuclear inclusion disease (NIID) who had an initial good levodopa response that was soon complicated by disabling dopa-induced dyskinesia. One child was diagnosed by rectal biopsy in life, and the other diagnosis was confirmed at postmortem. In this patient, dopamine transporter imaging showed severely decreased binding of the radiotracer in the striatum on both sides. Bilateral subthalamic deep brain stimulation in this patient produced initial improvement, but this was not sustained. Both patients died within 10 years of symptom onset. As well as levodopa responsiveness with rapid onset of dyskinesia, clues to the diagnosis of NIID in patients presenting with parkinsonism include the presence of gaze-evoked nystagmus, early onset dysarthria and dysphagia and oculogyric crises. Differential diagnosis of clinical symptoms and neuropathological findings are discussed including the approach to rectal biopsy for early diagnosis.

  18. Neuronal injury and cytogenesis after simple febrile seizures in the hippocampal dentate gyrus of juvenile rat.

    PubMed

    Nazem, Amir; Jafarian, Amir Hossein; Sadraie, Seyed Homayoon; Gorji, Ali; Kheradmand, Hamed; Radmard, Mahla; Haghir, Hossein

    2012-11-01

    Although simple febrile seizures are frequently described as harmless, there is evidence which suggests that hippocampal damage may occur after simple febrile seizures. This study aimed to investigate possible neuronal damages as well as alterations in cytogenesis in the hippocampal dentate gyrus following simple febrile seizures. Simple febrile seizure was modeled by hyperthermia-induced seizures in 22-day-old male rats. The brains were removed 2 or 15 days after hyperthermia in all rats with (n=20) and without (n=10) occurrence of seizures as well as in control animals (n=10). The sections were stained with hematoxylin and eosin to estimate the surface numerical density of dark neurons. Ki-67 immunohistochemistry was performed to evaluate changes of cytogenesis following simple febrile seizures. Hyperthermia induced behavioral seizure activities in 67 % of the rats. The numerical densities of dark neurons as well as the mean Ki-67 index (the fraction of Ki-67-positive cells) were significantly increased in dentate gyrus after induction of seizures by hyperthermia compared to both controls and rats without seizure after hyperthermia. Both the seizure duration and intensity were correlated significantly with numerical densities of dark neurons (but not with Ki-67 index). The data indicate that simple febrile seizures can cause neuronal damages and enhancement of cytogenesis in the hippocampal dentate gyrus, which were still visible for at least 2 weeks. These findings also suggest the correlation of febrile seizure intensity and duration with neuronal damage.

  19. Ceroid accumulation by murine peritoneal macrophages exposed to artificial lipoproteins: ultrastructural observations.

    PubMed Central

    Ball, R. Y.; Carpenter, K. L.; Mitchinson, M. J.

    1988-01-01

    Murine resident peritoneal macrophages were maintained in cell culture in a medium containing 10% lipoprotein-deficient fetal calf serum to which various artificial lipoprotein particles (coacervates of lipid and bovine serum albumin) had been added. The uptake and intracellular fate of these particles was studied by electron microscopy. The appearance of material accumulating within the cells varied according to the nature of the lipid component of the ingested particles. Lipids which are readily oxidised (cholesteryl linoleate, cholesteryl arachidonate, trilinolein) were associated with the formation of ceroid within membrane-bound structures. Less readily oxidized lipids (cholesteryl oleate, triolein) were not associated with ceroid accumulation but instead the cells contained numerous nonmembrane-bound lipid inclusions. The appearances of the ceroid within the murine peritoneal macrophages are similar to those of ceroid in macrophages in human atherosclerotic lesions. Images Fig. 8 Fig. 9 Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 10 PMID:3348959

  20. Laminar Differences in Dendritic Structure of Pyramidal Neurons in the Juvenile Rat Somatosensory Cortex.

    PubMed

    Rojo, Concepción; Leguey, Ignacio; Kastanauskaite, Asta; Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier; Benavides-Piccione, Ruth

    2016-06-01

    Pyramidal cell structure varies between different cortical areas and species, indicating that the cortical circuits that these cells participate in are likely to be characterized by different functional capabilities. Structural differences between cortical layers have been traditionally reported using either the Golgi method or intracellular labeling, but the structure of pyramidal cells has not previously been systematically analyzed across all cortical layers at a particular age. In the present study, we investigated the dendritic architecture of complete basal arbors of pyramidal neurons in layers II, III, IV, Va, Vb, and VI of the hindlimb somatosensory cortical region of postnatal day 14 rats. We found that the characteristics of basal dendritic morphologies are statistically different in each cortical layer. The variations in size and branching pattern that exist between pyramidal cells of different cortical layers probably reflect the particular functional properties that are characteristic of the cortical circuit in which they participate. This new set of complete basal dendritic arbors of 3D-reconstructed pyramidal cell morphologies across each cortical layer will provide new insights into interlaminar information processing in the cerebral cortex. © The Author 2016. Published by Oxford University Press.

  1. Laminar Differences in Dendritic Structure of Pyramidal Neurons in the Juvenile Rat Somatosensory Cortex

    PubMed Central

    Rojo, Concepción; Leguey, Ignacio; Kastanauskaite, Asta; Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier; Benavides-Piccione, Ruth

    2016-01-01

    Pyramidal cell structure varies between different cortical areas and species, indicating that the cortical circuits that these cells participate in are likely to be characterized by different functional capabilities. Structural differences between cortical layers have been traditionally reported using either the Golgi method or intracellular labeling, but the structure of pyramidal cells has not previously been systematically analyzed across all cortical layers at a particular age. In the present study, we investigated the dendritic architecture of complete basal arbors of pyramidal neurons in layers II, III, IV, Va, Vb, and VI of the hindlimb somatosensory cortical region of postnatal day 14 rats. We found that the characteristics of basal dendritic morphologies are statistically different in each cortical layer. The variations in size and branching pattern that exist between pyramidal cells of different cortical layers probably reflect the particular functional properties that are characteristic of the cortical circuit in which they participate. This new set of complete basal dendritic arbors of 3D-reconstructed pyramidal cell morphologies across each cortical layer will provide new insights into interlaminar information processing in the cerebral cortex. PMID:26762857

  2. Selective regulation of spontaneous activity of neurons of the deep cerebellar nuclei by N-type calcium channels in juvenile rats.

    PubMed

    Alviña, Karina; Khodakhah, Kamran

    2008-05-15

    The cerebellum coordinates movement and maintains body posture. The main output of the cerebellum is formed by three deep nuclei, which receive direct inhibitory inputs from cerebellar Purkinje cells, and excitatory collaterals from mossy and climbing fibres. Neurons of deep cerebellar nuclei (DCN) are spontaneously active, and disrupting their activity results in severe cerebellar ataxia. It is suggested that voltage-gated calcium channels make a significant contribution to the spontaneous activity of DCN neurons, although the exact identity of these channels is not known. We sought to delineate the functional role and identity of calcium channels that contribute to pacemaking in DCN neurons of juvenile rats. We found that in the majority of cells blockade of calcium currents results in avid high-frequency bursting, consistent with the notion that the net calcium-dependent current in DCN neurons is outward. We showed that the bursting seen in these neurons after block of calcium channels is the consequence of reduced activation of small-conductance calcium-activated (SK) potassium channels. With the use of selective pharmacological blockers we showed that L-, P/Q-, R- and T-type calcium channels do not contribute to the spontaneous activity of DCN neurons. In contrast, blockade of high-threshold N-type calcium channels increased the firing rate and caused the cells to burst. Our results thus suggest a selective coupling of N-type voltage-gated calcium channels with calcium-activated potassium channels in DCN neurons. In addition, we demonstrate the presence of a cadmium-sensitive calcium conductance coupled with SK channels, that is pharmacologically distinct from L-, N-, P/Q-, R- and T-type calcium channels.

  3. Efficacy of phosphodiesterase‐4 inhibitors in juvenile Batten disease (CLN3)

    PubMed Central

    Aldrich, Amy; Bosch, Megan E.; Fallet, Rachel; Odvody, Jessica; Burkovetskaya, Maria; Rama Rao, Kakulavarapu V.; Cooper, Jonathan D.; Drack, Arlene V.

    2016-01-01

    Objective Juvenile neuronal ceroid lipofuscinosis (JNCL), or juvenile Batten disease, is a pediatric lysosomal storage disease caused by autosomal recessive mutations in CLN3, typified by blindness, seizures, progressive cognitive and motor decline, and premature death. Currently, there is no treatment for JNCL that slows disease progression, which highlights the need to explore novel strategies to extend the survival and quality of life of afflicted children. Cyclic adenosine monophosphate (cAMP) is a second messenger with pleiotropic effects, including regulating neuroinflammation and neuronal survival. Here we investigated whether 3 phosphodiesterase‐4 (PDE4) inhibitors (rolipram, roflumilast, and PF‐06266047) could mitigate behavioral deficits and cell‐specific pathology in the Cln3Δex7/8 mouse model of JNCL. Methods In a randomized, blinded study, wild‐type (WT) and Cln3Δex7/8 mice received PDE4 inhibitors daily beginning at 1 or 3 months of age and continuing for 6 to 9 months, with motor deficits assessed by accelerating rotarod testing. The effect of PDE4 inhibitors on cAMP levels, astrocyte and microglial activation (glial fibrillary acidic protein and CD68, respectively), lysosomal pathology (lysosomal‐associated membrane protein 1), and astrocyte glutamate transporter expression (glutamate/aspartate transporter) were also examined in WT and Cln3Δex7/8 animals. Results cAMP levels were significantly reduced in the Cln3Δex7/8 brain, and were restored by PF‐06266047. PDE4 inhibitors significantly improved motor function in Cln3Δex7/8 mice, attenuated glial activation and lysosomal pathology, and restored glutamate transporter expression to levels observed in WT animals, with no evidence of toxicity as revealed by blood chemistry analysis. Interpretation These studies reveal neuroprotective effects for PDE4 inhibitors in Cln3Δex7/8 mice and support their therapeutic potential in JNCL patients. Ann Neurol 2016;80:909–923 PMID:27804148

  4. Wolman's Disease: A Microscopic and Biochemical Study Showing Accumulation of Ceroid and Esterified Cholesterol

    PubMed Central

    Lowden, J. A.; Barson, A. J.; Wentworth, P.

    1970-01-01

    A case of Wolman's disease is described in a female infant who died at 7 weeks of age. This rare familial disorder is characterized by bilateral adrenal calcification and the accumulation of esterified cholesterol in many tissues. For the first time large quantities of ceroid have been demonstrated in the liver, spleen, adrenals, lymph nodes and particularly within the lamina propria of the small intestine. It is postulated that there exists in these patients a decreased activity of cholesterol esterases. The accumulated cholesterol esters may then be oxidized to form ceroid. Since ceroid is quite impermeable, intestinal absorption is progressively impaired, leading ultimately to death. ImagesFIG. 1FIG. 2FIG. 3 PMID:5414926

  5. A central role for TOR signalling in a yeast model for juvenile CLN3 disease

    PubMed Central

    Bond, Michael E.; Brown, Rachel; Rallis, Charalampos; Bähler, Jürg; Mole, Sara E.

    2015-01-01

    Yeasts provide an excellent genetically tractable eukaryotic system for investigating the function of genes in their biological context, and are especially relevant for those conserved genes that cause disease. We study the role of btn1, the orthologue of a human gene that underlies an early onset neurodegenerative disease (juvenile CLN3 disease, neuronal ceroid lipofuscinosis (NCLs) or Batten disease) in the fission yeast Schizosaccharomyces pombe. A global screen for genetic interactions with btn1 highlighted a conserved key signalling hub in which multiple components functionally relate to this conserved disease gene. This signalling hub includes two major mitogen-activated protein kinase (MAPK) cascades, and centers on the Tor kinase complexes TORC1 and TORC2. We confirmed that yeast cells modelling CLN3 disease exhibit features consistent with dysfunction in the TORC pathways, and showed that modulating TORC function leads to a comprehensive rescue of defects in this yeast disease model. The same pathways may be novel targets in the development of therapies for the NCLs and related diseases. PMID:28357272

  6. Juvenile angiofibroma

    MedlinePlus

    Nasal tumor; Angiofibroma - juvenile; Benign nasal tumor; Juvenile nasal angiofibroma; JNA ... Juvenile angiofibroma is not very common. It is most often found in adolescent boys. The tumor contains ...

  7. Accumulation of ceroid in smooth muscle indicates severe malabsorption and vitamin E deficiency.

    PubMed Central

    Stamp, G W; Evans, D J

    1987-01-01

    Four patients had accumulation of ceroid in smooth muscle (lipofuscinosis), which indicated severe or uncontrolled malabsorption, with confirmed vitamin E deficiency in three cases. The distribution of the pigment was systematic, and there seemed to be an association between malabsorption syndrome and vitamin E deficiency. Vitamin E supplementation seems to be indicated in such patients, and it is suggested that studies of smooth muscle function should be made in cases of heavy accumulation of ceroid. Images Fig 1 Fig 2 Fig 3 Fig 4 Fig 5 PMID:3624501

  8. Osmotic Edema Rapidly Increases Neuronal Excitability Through Activation of NMDA Receptor-Dependent Slow Inward Currents in Juvenile and Adult Hippocampus

    PubMed Central

    Lauderdale, Kelli; Murphy, Thomas; Tung, Tina; Davila, David; Binder, Devin K.

    2015-01-01

    Cellular edema (cell swelling) is a principal component of numerous brain disorders including ischemia, cortical spreading depression, hyponatremia, and epilepsy. Cellular edema increases seizure-like activity in vitro and in vivo, largely through nonsynaptic mechanisms attributable to reduction of the extracellular space. However, the types of excitability changes occurring in individual neurons during the acute phase of cell volume increase remain unclear. Using whole-cell patch clamp techniques, we report that one of the first effects of osmotic edema on excitability of CA1 pyramidal cells is the generation of slow inward currents (SICs), which initiate after approximately 1 min. Frequency of SICs increased as osmolarity decreased in a dose-dependent manner. Imaging of real-time volume changes in astrocytes revealed that neuronal SICs occurred while astrocytes were still in the process of swelling. SICs evoked by cell swelling were mainly nonsynaptic in origin and NMDA receptor-dependent. To better understand the relationship between SICs and changes in neuronal excitability, recordings were performed in increasingly physiological conditions. In the absence of any added pharmacological reagents or imposed voltage clamp, osmotic edema induced excitatory postsynaptic potentials and burst firing over the same timecourse as SICs. Like SICs, action potentials were blocked by NMDAR antagonists. Effects were more pronounced in adult (8–20 weeks old) compared with juvenile (P15–P21) mice. Together, our results indicate that cell swelling triggered by reduced osmolarity rapidly increases neuronal excitability through activation of NMDA receptors. Our findings have important implications for understanding nonsynaptic mechanisms of epilepsy in relation to cell swelling and reduction of the extracellular space. PMID:26489684

  9. Mechanism of ceroid formation in atherosclerotic plaque: in situ studies using a combination of Raman and fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Haka, Abigail S.; Kramer, John R.; Dasari, Ramachandra R.; Fitzmaurice, Maryann

    2011-01-01

    Accumulation of the lipid-protein complex ceroid is a characteristic of atherosclerotic plaque. The mechanism of ceroid formation has been extensively studied, because the complex is postulated to contribute to plaque irreversibility. Despite intensive research, ceroid deposits are defined through their fluorescence and histochemical staining properties, while their composition remains unknown. Using Raman and fluorescence spectral microscopy, we examine the composition of ceroid in situ in aorta and coronary artery plaque. The synergy of these two types of spectroscopy allows for identification of ceroid via its fluorescence signature and elucidation of its chemical composition through the acquisition of a Raman spectrum. In accordance with in vitro predictions, low density lipoprotein (LDL) appears within the deposits primarily in its peroxidized form. The main forms of modified LDL detected in both coronary artery and aortic plaques are peroxidation products from the Fenton reaction and myeloperoxidase-hypochlorite pathway. These two peroxidation products occur in similar concentrations within the deposits and represent ~40 and 30% of the total LDL (native and peroxidized) in the aorta and coronary artery deposits, respectively. To our knowledge, this study is the first to successfully employ Raman spectroscopy to unravel a metabolic pathway involved in disease pathogenesis: the formation of ceroid in atherosclerotic plaque.

  10. Mechanism of ceroid formation in atherosclerotic plaque: in situ studies using a combination of Raman and fluorescence spectroscopy

    PubMed Central

    Haka, Abigail S.; Kramer, John R.; Dasari, Ramachandra R.; Fitzmaurice, Maryann

    2011-01-01

    Accumulation of the lipid-protein complex ceroid is a characteristic of atherosclerotic plaque. The mechanism of ceroid formation has been extensively studied, because the complex is postulated to contribute to plaque irreversibility. Despite intensive research, ceroid deposits are defined through their fluorescence and histochemical staining properties, while their composition remains unknown. Using Raman and fluorescence spectral microscopy, we examine the composition of ceroid in situ in aorta and coronary artery plaque. The synergy of these two types of spectroscopy allows for identification of ceroid via its fluorescence signature and elucidation of its chemical composition through the acquisition of a Raman spectrum. In accordance with in vitro predictions, low density lipoprotein (LDL) appears within the deposits primarily in its peroxidized form. The main forms of modified LDL detected in both coronary artery and aortic plaques are peroxidation products from the Fenton reaction and myeloperoxidase-hypochlorite pathway. These two peroxidation products occur in similar concentrations within the deposits and represent ∼40 and 30% of the total LDL (native and peroxidized) in the aorta and coronary artery deposits, respectively. To our knowledge, this study is the first to successfully employ Raman spectroscopy to unravel a metabolic pathway involved in disease pathogenesis: the formation of ceroid in atherosclerotic plaque. PMID:21280898

  11. The effects of amphetamine exposure on juvenile rats on the neuronal morphology of the limbic system at prepubertal, pubertal and postpubertal ages.

    PubMed

    Tendilla-Beltrán, Hiram; Arroyo-García, Luis Enrique; Diaz, Alfonso; Camacho-Abrego, Israel; de la Cruz, Fidel; Rodríguez-Moreno, Antonio; Flores, Gonzalo

    2016-11-01

    Amphetamines (AMPH) are psychostimulants widely used for therapy as well as for recreational purposes. Previous results of our group showed that AMPH exposure in pregnant rats induces physiological and behavioral changes in the offspring at prepubertal and postpubertal ages. In addition, several reports have shown that AMPH are capable of modifying the morphology of neurons in some regions of the limbic system. These modifications can cause some psychiatric conditions. However, it is still unclear if there are changes to behavioral and morphological levels when low doses of AMPH are administered at a juvenile age. The aim of this study was to assess the effect of AMPH administration (1mg/kg) in Sprague-Dawley rats (postnatal day, PD21-PD35) on locomotor activity in a novel environment and compare the neuronal morphology of limbic system areas at three different ages: prepubertal (PD 36), pubertal (PD50) and postpubertal (PD 62). We found that AMPH altered locomotor activity in the prepubertal group, but did not have an effect on the other two age groups. The Golgi-Cox staining method was used to describe the neural morphology of five limbic regions: (Layers 3 and 5) the medial prefrontal cortex (mPFC), the dorsal and ventral hippocampus, the nucleus accumbens and the amygdala, showing that AMPH induced changes at pubertal ages in arborization and spine density of these neurons, but interestingly these changes did not persist at postpubertal ages. Our findings suggest that even early-life AMPH exposure does not induce long-term behavioral and morphological changes, however it causes alterations at pubertal ages in the limbic system networks, a stage of life strongly associated with the development of substance abuse behaviors. Copyright © 2016. Published by Elsevier B.V.

  12. Juvenile Arthritis

    MedlinePlus

    ... A Patient / Caregiver Diseases & Conditions Juvenile Arthritis Juvenile Arthritis Fast Facts Arthritis in children is treatable. It ... as fevers or rash. What is juvenile idiopathic arthritis? Several types of arthritis, all involving chronic (long- ...

  13. Shifts in excitatory/inhibitory balance by juvenile stress: A role for neuron-astrocyte interaction in the dentate gyrus.

    PubMed

    Albrecht, Anne; Ivens, Sebastian; Papageorgiou, Ismini E; Çalışkan, Gürsel; Saiepour, Nasrin; Brück, Wolfgang; Richter-Levin, Gal; Heinemann, Uwe; Stork, Oliver

    2016-06-01

    Childhood trauma is a well-described risk factor for the development of stress-related psychopathology such as posttraumatic stress disorder or depression later in life. Childhood adversity can be modeled in rodents by juvenile stress (JS) protocols, resulting in impaired coping with stressful challenges in adulthood. In the current study, we investigated the long-lasting impact of JS on the expression of molecular factors for glutamate and γ-aminobutyric acid (GABA) uptake and turnover in sublayers of the dentate gyrus (DG) using laser microdissection and quantitative real-time polymerase chain reaction. We observed reduced mRNA expression levels after JS for factors mediating astrocytic glutamate and GABA uptake and degradation. These alterations were prominently observed in the dorsal but not ventral DG granule cell layer, indicating a lasting change in astrocytic GABA and glutamate metabolism that may affect dorsal DG network activity. Indeed, we observed increased inhibition and a lack of facilitation in response to paired-pulse stimulation at short interstimulus intervals in the dorsal DG after JS, while no alterations were evident in basal synaptic transmission or forms of long-term plasticity. The shift in paired-pulse response was mimicked by pharmacologically blocking the astrocytic GABA transporter GAT-3 in naïve animals. Accordingly, reduced expression levels of GAT-3 were confirmed at the protein level in the dorsal granule cell layer of rats stressed in juvenility. Together, these data demonstrate a lasting shift in the excitatory/inhibitory balance of dorsal DG network activity by JS that appears to be mediated by decreased GABA uptake into astrocytes.

  14. Genetics Home Reference: CLN3 disease

    MedlinePlus

    ... role in regulating anterograde and retrograde post-Golgi trafficking. Clin Lipidol. 2012 Feb;7(1):79-91. ... D, Hermey G. Revisiting the neuronal localization and trafficking of CLN3 in juvenile neuronal ceroid lipofuscinosis. J ...

  15. Electrophysiological characterization of synaptic connections between layer VI cortical cells and neurons of the nucleus reticularis thalami in juvenile rats.

    PubMed

    Gentet, Luc J; Ulrich, Daniel

    2004-02-01

    Corticothalamic (CT) feedback projections to the thalamus outnumber sensory inputs from the periphery by orders of magnitude. However, their functional role remains elusive. CT projections may directly excite thalamic relay cells or indirectly inhibit them via excitation of the nucleus reticularis thalami (nRT), a nuclear formation composed entirely of gamma-aminobutyric acidergic neurons. The relative strengths of these two pathways will ultimately control the effects of CT projections on the output of thalamic relay cells. However, corticoreticular synapses have not yet been fully physiologically characterized. Here, local stimulation of layer VI cells by focal application of K+ or AMPA elicited excitatory postsynaptic potentials in nRT neurons with a mean peak amplitude of 2.4 +/- 0.1 mV (n = 75, mean +/- SEM), a mean rise time (10-90%) of 0.74 +/- 0.03 ms and a weighted decay time constant of 11 +/- 0.3 ms. A pharmacological profile of responses was drawn in both current-clamp and voltage-clamp modes, showing the presence of a small N-methyl-d-aspartate receptor-dependent component at depolarized potentials. In two pairs of synaptically coupled layer VI cell-nRT neuron, moderate rates of transmission failures were observed while the latencies were above 5 ms in both cases. Our results indicate that the corticoreticular pathway fulfills the criteria for 'modulatory' inputs and is temporally restricted. We suggest that it may be involved in coincidence detection of convergent corticoreticular signals.

  16. Proteomic mapping of differentially vulnerable pre-synaptic populations identifies regulators of neuronal stability in vivo.

    PubMed

    Llavero Hurtado, Maica; Fuller, Heidi R; Wong, Andrew M S; Eaton, Samantha L; Gillingwater, Thomas H; Pennetta, Giuseppa; Cooper, Jonathan D; Wishart, Thomas M

    2017-09-29

    Synapses are an early pathological target in many neurodegenerative diseases ranging from well-known adult onset conditions such as Alzheimer and Parkinson disease to neurodegenerative conditions of childhood such as spinal muscular atrophy (SMA) and neuronal ceroid lipofuscinosis (NCLs). However, the reasons why synapses are particularly vulnerable to such a broad range of neurodegeneration inducing stimuli remains unknown. To identify molecular modulators of synaptic stability and degeneration, we have used the Cln3 (-/-) mouse model of a juvenile form of NCL. We profiled and compared the molecular composition of anatomically-distinct, differentially-affected pre-synaptic populations from the Cln3 (-/-) mouse brain using proteomics followed by bioinformatic analyses. Identified protein candidates were then tested using a Drosophila CLN3 model to study their ability to modify the CLN3-neurodegenerative phenotype in vivo. We identified differential perturbations in a range of molecular cascades correlating with synaptic vulnerability, including valine catabolism and rho signalling pathways. Genetic and pharmacological targeting of key 'hub' proteins in such pathways was sufficient to modulate phenotypic presentation in a Drosophila CLN3 model. We propose that such a workflow provides a target rich method for the identification of novel disease regulators which could be applicable to the study of other conditions where appropriate models exist.

  17. Unbiased Cell-based Screening in a Neuronal Cell Model of Batten Disease Highlights an Interaction between Ca2+ Homeostasis, Autophagy, and CLN3 Protein Function*

    PubMed Central

    Chandrachud, Uma; Walker, Mathew W.; Simas, Alexandra M.; Heetveld, Sasja; Petcherski, Anton; Klein, Madeleine; Oh, Hyejin; Wolf, Pavlina; Zhao, Wen-Ning; Norton, Stephanie; Haggarty, Stephen J.; Lloyd-Evans, Emyr; Cotman, Susan L.

    2015-01-01

    Abnormal accumulation of undigested macromolecules, often disease-specific, is a major feature of lysosomal and neurodegenerative disease and is frequently attributed to defective autophagy. The mechanistic underpinnings of the autophagy defects are the subject of intense research, which is aided by genetic disease models. To gain an improved understanding of the pathways regulating defective autophagy specifically in juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease), a neurodegenerative disease of childhood, we developed and piloted a GFP-microtubule-associated protein 1 light chain 3 (GFP-LC3) screening assay to identify, in an unbiased fashion, genotype-sensitive small molecule autophagy modifiers, employing a JNCL neuronal cell model bearing the most common disease mutation in CLN3. Thapsigargin, a sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) Ca2+ pump inhibitor, reproducibly displayed significantly more activity in the mouse JNCL cells, an effect that was also observed in human-induced pluripotent stem cell-derived JNCL neural progenitor cells. The mechanism of thapsigargin sensitivity was Ca2+-mediated, and autophagosome accumulation in JNCL cells could be reversed by Ca2+ chelation. Interrogation of intracellular Ca2+ handling highlighted alterations in endoplasmic reticulum, mitochondrial, and lysosomal Ca2+ pools and in store-operated Ca2+ uptake in JNCL cells. These results further support an important role for the CLN3 protein in intracellular Ca2+ handling and in autophagic pathway flux and establish a powerful new platform for therapeutic screening. PMID:25878248

  18. Visual deficits in a mouse model of Batten disease are the result of optic nerve degeneration and loss of dorsal lateral geniculate thalamic neurons

    PubMed Central

    Weimer, Jill M.; Custer, Andrew W.; Benedict, Jared W.; Alexander, Noreen A.; Kingsley, Evan; Federoff, Howard J.; Cooper, Jonathan D.; Pearce, David A.

    2013-01-01

    Juvenile neuronal ceroid lipofuscinosis (JNCL) is an autosomal recessive disorder of childhood caused by mutations in CLN3. Although visual deterioration is typically the first clinical sign to manifest in affected children, loss of Cln3 in a mouse model of JNCL does not recapitulate this retinal deterioration. This suggests that either the loss of CLN3 does not directly affect retinal cell survival or that nuclei involved in visual processing are affected prior to retinal degeneration. Having previously demonstrated that Cln3−/− mice have decreased optic nerve axonal density, we now demonstrate a decrease in nerve conduction. Examination of retino-recipient regions revealed a decreased number of neurons within the dorsal lateral geniculate nucleus (LGNd). We demonstrate decreased transport of amino acids from the retina to the LGN, suggesting an impediment in communication between the retina and projection nuclei. This study defines a novel path of degeneration within the LGNd, providing a mechanism for causation of JNCL visual deficits. PMID:16412658

  19. Genetics Home Reference: juvenile primary lateral sclerosis

    MedlinePlus

    ... primary lateral sclerosis juvenile Merck Manual Consumer Version: Amyotrophic Lateral Sclerosis and Other Motor Neuron Diseases Patient Support and ... domains, is mutated in a form of recessive amyotrophic lateral sclerosis. Nat Genet. 2001 Oct;29(2):160-5. ...

  20. Juvenile Arthritis

    MedlinePlus

    Juvenile arthritis (JA) is arthritis that happens in children. It causes joint swelling, pain, stiffness, and loss of motion. It can affect any joint, but ... of JA that children get is juvenile idiopathic arthritis. There are several other forms of arthritis affecting ...

  1. Juvenile Firesetting.

    PubMed

    Peters, Brittany; Freeman, Bradley

    2016-01-01

    Juvenile firesetting is a significant cause of morbidity and mortality in the United States. Male gender, substance use, history of maltreatment, interest in fire, and psychiatric illness are commonly reported risk factors. Interventions that have been shown to be effective in juveniles who set fires include cognitive behavior therapy and educational interventions, whereas satiation has not been shown to be an effective intervention. Forensic assessments can assist the legal community in adjudicating youth with effective interventions. Future studies should focus on consistent assessment and outcome measures to create more evidence for directing evaluation and treatment of juvenile firesetters.

  2. [Anomalies in fatty acids distribution and superoxide dismutase activity in lymphocytes of an adult with atypical ceroid lipofuscinosis].

    PubMed

    Rumbach, L; Warter, J M; Coquillat, G; Marescaux, C; Collard, M; Rohmer, F; Bieth, R; Zawislak, R

    1983-01-01

    A 27-year-old Algerian patient presented a slowly progressive disease clinically characterized by a cerebellar syndrome, absence of deep reflexes, bilateral sign of Babinski, deep sensory disturbances, ophthalmologic disorders and pes cavus. The diagnosis of ceroid lipofuscinosis resulted from the presence of lipofuscin deposits evidenced as autofluorescent bodies, and a particular type of curvilinear, crystalloid ultrastructural inclusion bodies in muscle, lymphocytes and liver. Biochemical tests showed reduction in levels of linoleic and arachidonic acids, and of superoxide dismutase activity in lymphocytes. These findings suggest that the biochemical anomalies result from disturbances in polyunsaturated fatty acids metabolism. These results can be related to pathogenetic hypotheses for ceroid lipofuscinosis suggesting a predominant role for peroxidation of fatty acids.

  3. Dermatomyositis (Juvenile)

    MedlinePlus

    ... of children with JDM may have a more chronic course that is less responsive to therapy. Juvenile ... disease and arthritis. Since the myopathies can be chronic diseases, it is important for patients to have ...

  4. Juvenile Prostitution.

    ERIC Educational Resources Information Center

    Csapo, Marg

    1986-01-01

    Recent research and Canadian government committee reports concerning juvenile prostitution are reviewed. Proposals are made in the realms of law and social policy; and existing programs are described. (DB)

  5. Juvenile Idiopathic Arthritis

    MedlinePlus

    ... Is Juvenile Idiopathic Arthritis the same as Juvenile Rheumatoid Arthritis? Yes, Juvenile Idiopathic Arthritis (JIA) is a new ... of chronic inflammatory diseases that affect children. Juvenile Rheumatoid Arthritis (JRA) is the older term that was used ...

  6. Juvenile Spondyloarthritis

    PubMed Central

    Gmuca, Sabrina; Weiss, Pamela F.

    2015-01-01

    Purpose of review To provide a comprehensive update of the pathogenesis, diagnostic imaging, treatments, and disease activity measurements of juvenile spondyloarthritis (JSpA). Recent findings Genetic and microbiome studies have provided new information regarding possible pathogenesis of JSpA. Recent work suggests that children with JSpA have decreased thresholds for pain in comparison to healthy children. Additionally, pain on physical examination and abnormalities on ultrasound of the entheses are not well correlated. Treatment guidelines for juvenile arthritis, including JSpA, were published by the American College of Rheumatology and are based on active joint count and presence of sacroiliitis. Recent studies have established the efficacy of tumor necrosis factor inhibitors in the symptomatic treatment of axial disease, though their efficacy for halting progression of structural damage is less clear. Newly developed disease activity measures for JSpA include the Juvenile Arthritis Disease Activity Score and the JSpA Disease Activity index. In comparison to other categories of juvenile arthritis, children with JSpA are less likely to attain and sustain inactive disease. Summary Further microbiome and genetic research may help elucidate JSpA pathogenesis. More randomized therapeutic trials are needed and the advent of new composite disease activity measurement tools will hopefully allow for the design of these greatly needed trials. PMID:26002028

  7. Juvenile Justice in Milwaukee

    ERIC Educational Resources Information Center

    Williams, Gary L.; Greer, Lanetta

    2010-01-01

    Historically, there have been several attempts made to address issues surrounding juvenile delinquency. The Wisconsin Legislature outlines the objectives of the juvenile justice system in the Juvenile Justice Code in s. 939.01, ?to promote a juvenile justice system capable of dealing with the problem of juvenile delinquency, a system which will…

  8. Juvenile xanthogranuloma.

    PubMed

    Singh, R; Ghazali, W

    1992-05-01

    Juvenile xanthogranuloma is a benign cutaneous growth presenting as papules or nodules. It is characterized by an intradermal collection of lipid-laden macrophages and varying degrees of fibroblastic proliferation. We have recently observed two patients with xanthogranulomas: one was found to have a papular type and the second patient had multiple nodular growths. We present these cases, which should be considered in the differential diagnosis of skin nodules.

  9. Kupffer cell structure in the juvenile Nile crocodile, Crocodylus niloticus.

    PubMed

    van Wilpe, Erna; Groenewald, Hermanus Bernardus

    2014-01-01

    The morphology of Kupffer cells was examined in the liver of the juvenile Nile crocodile using light microscopy and transmission electron microscopy. Pleomorphic Kupffer cells were located in the sinusoids, in the space of Disse, in the hepatic parenchyma and often connected adjacent sinusoids. The cell surfaces were irregular due to the presence of filopodia and lamelliapodia with phagocytosis of white blood cells, red blood cells and thrombocytes being evident. The cells were in close contact with endothelial cells and pit cells in the sinusoidal lumen and with stellate cells in the space of Disse. The cytoplasm contained large phagosomes comprising a combination of ceroid pigment, melanosomes and siderosomes. The nuclei were often indented and eccentrically placed due to the presence of the phagosomes. Conspicuous clusters of membrane-bound tubular organelles with a filamentous or crystalline interior were observed in the cytoplasm. The clusters were sometimes separated into smaller groups around phagosomes. A clear zone existed between the limiting membrane and the interior of these tubular organelles with the electron-dense interior profiles being, respectively, circular, angular or divided. The tubular organelles have not previously been described in Kupffer cells and possibly represent lysosomes with specialized functions. Mitochondria, microtubules, Golgi profiles, granular and smooth endoplasmic reticulum, and a few cytoplasmic lipid droplets were also present. The presence of the tubular organelles and the occurrence of the Kupffer cells in different locations in the liver of the juvenile Nile crocodile are indicative of particularly active and mobile cells. Copyright © 2013 Wiley Periodicals, Inc.

  10. Juvenile Idiopathic Arthritis

    MedlinePlus

    ... for You Healthy School Lunch Planner Juvenile Idiopathic Arthritis (JIA) KidsHealth > For Teens > Juvenile Idiopathic Arthritis (JIA) ... people under age 17. What Is Juvenile Idiopathic Arthritis? Arthritis doesn't affect young people as much ...

  11. Juvenile rheumatoid arthritis

    MedlinePlus

    ... joints. This form of JIA may turn into rheumatoid arthritis. It may involve five or more large and ... no known prevention for JIA. Alternative Names Juvenile rheumatoid arthritis (JRA); Juvenile chronic polyarthritis; Still disease; Juvenile spondyloarthritis ...

  12. Juvenile Idiopathic Arthritis

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Juvenile Idiopathic Arthritis (JIA) KidsHealth > For Teens > Juvenile Idiopathic ... can affect people under age 17. What Is Juvenile Idiopathic Arthritis? Arthritis doesn't affect young people ...

  13. Fighting Juvenile Gun Violence. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Sheppard, David; Grant, Heath; Rowe, Wendy; Jacobs, Nancy

    This bulletin describes the Office of Juvenile Justice and Delinquency Prevention's efforts to fight juvenile gun violence. The Office awarded four community demonstration grants to implement "Partnerships To Reduce Juvenile Gun Violence." Partnership goals include increasing the effectiveness of existing strategies by enhancing and…

  14. Juvenile Justice & Youth Violence.

    ERIC Educational Resources Information Center

    Howell, James C.

    Youth violence and the juvenile justice system in the United States are explored. Part 1 takes stock of the situation. The first chapter discusses the origins and evaluation of the juvenile justice system, and the second considers the contributions of the Federal Juvenile Justice and Delinquency Prevention Act to the existing juvenile justice…

  15. Juvenile Justice & Youth Violence.

    ERIC Educational Resources Information Center

    Howell, James C.

    Youth violence and the juvenile justice system in the United States are explored. Part 1 takes stock of the situation. The first chapter discusses the origins and evaluation of the juvenile justice system, and the second considers the contributions of the Federal Juvenile Justice and Delinquency Prevention Act to the existing juvenile justice…

  16. Treating Juvenile Crime.

    ERIC Educational Resources Information Center

    Gelber, Seymour

    1983-01-01

    Although juvenile crime rates have not changed significantly in the last five years, the juvenile courts' ability to handle crime has deteriorated. To treat the problem of juvenile crime effectively requires intervention at the earliest sign of delinquency and an assessment of the juvenile courts and school system. (AM)

  17. Lysosomal storage of subunit c of mitochondrial ATP synthase in Batten's disease (ceroid-lipofuscinosis).

    PubMed Central

    Hall, N A; Lake, B D; Dewji, N N; Patrick, A D

    1991-01-01

    Immunochemical studies demonstrate that subunit c of mitochondrial ATP synthase is stored in the late-infantile, juvenile and adult forms of Batten's disease. It does not accumulate in the infantile form, or in other conditions involving lysosomal hypertrophy. These results suggest that the defective metabolism of subunit c is central to the pathogenesis of these three forms of Batten's disease. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:1826833

  18. Juvenile Delinquency: An Introduction

    ERIC Educational Resources Information Center

    Smith, Carolyn A.

    2008-01-01

    Juvenile Delinquency is a term which is often inaccurately used. This article clarifies definitions, looks at prevalence, and explores the relationship between juvenile delinquency and mental health. Throughout, differences between males and females are explored. (Contains 1 table.)

  19. Juvenile Delinquency: An Introduction

    ERIC Educational Resources Information Center

    Smith, Carolyn A.

    2008-01-01

    Juvenile Delinquency is a term which is often inaccurately used. This article clarifies definitions, looks at prevalence, and explores the relationship between juvenile delinquency and mental health. Throughout, differences between males and females are explored. (Contains 1 table.)

  20. Juvenile Arrests, 2000. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Snyder, Howard N.

    This bulletin examines the national and state juvenile arrest rate in 2000 using data reported annually by local law enforcement agencies nationwide to the FBI's Uniform Crime Reporting program. Results indicate that the murder rate in 2000 was the lowest since 1965; juvenile arrests for violence in 2000 were the lowest since 1988; few juveniles…

  1. Juvenile Arrests, 2007. Juvenile Justice Bulletin

    ERIC Educational Resources Information Center

    Puzzanchera, Charles

    2009-01-01

    This Bulletin summarizes 2007 juvenile crime and arrest data reported by local law enforcement agencies across the country and cited in the FBI report, "Crime in the United States 2007." The Bulletin describes the extent and nature of juvenile crime that comes to the attention of the justice system. It serves as a baseline for comparison for…

  2. Juvenile Arrests, 1998. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Snyder, Howard N.

    This report provides a summary and analysis of national and state juvenile arrest data in the United States. In 1998, law enforcement agencies made an estimated 2.6 million arrests of persons under age 18. Federal Bureau of Investigations statistics indicate that juveniles account for 18% of all arrests, and 17% of all violent crime arrests in…

  3. Juvenile Arrests, 1999. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Snyder, Howard N.

    This bulletin presents a summary and analysis of national and state juvenile arrest data for 1999. Data come from the FBI's annual "Crime in the United States" report, which offers the estimated number of crimes reported to law enforcement agencies. The 1999 murder rate was the lowest since 1966. Of the nearly 1,800 juveniles murdered in…

  4. Juvenile Arrests 1996. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Snyder, Howard N.

    In 1996, law enforcement agencies in the United States made an estimated 2.9 million arrests of persons under the age of 18. According to Federal Bureau of Investigation (FBI) figures, juveniles accounted for 19% of all arrests and 19% of all violent crime in 1996. The substantial growth in juvenile crime that began in the late 1980s peaked in…

  5. Juvenile Justice Glossary.

    ERIC Educational Resources Information Center

    Update on Law-Related Education, 2000

    2000-01-01

    Provides a list of terms pertaining to the juvenile justice system, such as appeal and due process, that are used throughout this edition of "Update on Law-Related Education," in particular, with the teaching strategies "The Case of Gerry Gault" (SO 532 196) "Today's Juvenile Court" (SO 532 197), and "Using the Juvenile Justice Poster" (SO 532…

  6. Concepts Shaping Juvenile Justice

    ERIC Educational Resources Information Center

    White, Rob

    2008-01-01

    Rob White's paper explores ways in which community building can be integrated into the practices of juvenile justice work. He provides a model of what can be called "restorative social justice", one that builds upon the juvenile conferencing model by attempting to fuse social justice concerns with progressive juvenile justice practices.

  7. Altered Sensory Code Drives Juvenile-to-Adult Behavioral Maturation in Caenorhabditis elegans

    PubMed Central

    Pantazis, Alexandros K.

    2016-01-01

    Abstract Adults perform better than juveniles in food-seeking tasks. Using the nematode Caenorhabditis elegans to probe the neural mechanisms underlying behavioral maturation, we found that adults and juveniles require different combinations of sensory neurons to generate age-specific food-seeking behavior. We first show that adults and juveniles differ in their response to and preference for food-associated odors, and we analyze genetic mutants to map the neuronal circuits required for those behavioral responses. We developed a novel device to trap juveniles and record their neuronal activity. Activity measurements revealed that adult and juvenile AWA sensory neurons respond to the addition of diacetyl stimulus, whereas AWB, ASK, and AWC sensory neurons encode its removal specifically in adults. Further, we show that reducing neurotransmission from the additional AWB, ASK, and AWC sensory neurons transforms odor preferences from an adult to a juvenile-like state. We also show that AWB and ASK neurons drive behavioral changes exclusively in adults, providing more evidence that age-specific circuits drive age-specific behavior. Collectively, our results show that an odor-evoked sensory code is modified during the juvenile-to-adult transition in animal development to drive age-appropriate behavior. We suggest that this altered sensory code specifically enables adults to extract additional stimulus features and generate robust behavior. PMID:28083560

  8. Juvenile polyposis syndrome.

    PubMed

    Brosens, Lodewijk Aa; Langeveld, Danielle; van Hattem, W Arnout; Giardiello, Francis M; Offerhaus, G Johan A

    2011-11-28

    Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer. The cumulative life-time risk of colorectal cancer is 39% and the relative risk is 34. Juvenile polyps have a distinctive histology characterized by an abundance of edematous lamina propria with inflammatory cells and cystically dilated glands lined by cuboidal to columnar epithelium with reactive changes. Clinically, juvenile polyposis syndrome is defined by the presence of 5 or more juvenile polyps in the colorectum, juvenile polyps throughout the gastrointestinal tract or any number of juvenile polyps and a positive family history of juvenile polyposis. In about 50%-60% of patients diagnosed with juvenile polyposis syndrome a germline mutation in the SMAD4 or BMPR1A gene is found. Both genes play a role in the BMP/TGF-beta signalling pathway. It has been suggested that cancer in juvenile polyposis may develop through the so-called "landscaper mechanism" where an abnormal stromal environment leads to neoplastic transformation of the adjacent epithelium and in the end invasive carcinoma. Recognition of this rare disorder is important for patients and their families with regard to treatment, follow-up and screening of at risk individuals. Each clinician confronted with the diagnosis of a juvenile polyp should therefore consider the possibility of juvenile polyposis syndrome. In addition, juvenile polyposis syndrome provides a unique model to study colorectal cancer pathogenesis in general and gives insight in the molecular genetic basis of cancer. This review discusses clinical manifestations, genetics, pathogenesis and management of juvenile polyposis syndrome.

  9. Juvenile polyposis syndrome

    PubMed Central

    Brosens, Lodewijk AA; Langeveld, Danielle; van Hattem, W Arnout; Giardiello, Francis M; Offerhaus, G Johan A

    2011-01-01

    Juvenile polyposis syndrome is a rare autosomal dominant syndrome characterized by multiple distinct juvenile polyps in the gastrointestinal tract and an increased risk of colorectal cancer. The cumulative life-time risk of colorectal cancer is 39% and the relative risk is 34. Juvenile polyps have a distinctive histology characterized by an abundance of edematous lamina propria with inflammatory cells and cystically dilated glands lined by cuboidal to columnar epithelium with reactive changes. Clinically, juvenile polyposis syndrome is defined by the presence of 5 or more juvenile polyps in the colorectum, juvenile polyps throughout the gastrointestinal tract or any number of juvenile polyps and a positive family history of juvenile polyposis. In about 50%-60% of patients diagnosed with juvenile polyposis syndrome a germline mutation in the SMAD4 or BMPR1A gene is found. Both genes play a role in the BMP/TGF-beta signalling pathway. It has been suggested that cancer in juvenile polyposis may develop through the so-called “landscaper mechanism” where an abnormal stromal environment leads to neoplastic transformation of the adjacent epithelium and in the end invasive carcinoma. Recognition of this rare disorder is important for patients and their families with regard to treatment, follow-up and screening of at risk individuals. Each clinician confronted with the diagnosis of a juvenile polyp should therefore consider the possibility of juvenile polyposis syndrome. In addition, juvenile polyposis syndrome provides a unique model to study colorectal cancer pathogenesis in general and gives insight in the molecular genetic basis of cancer. This review discusses clinical manifestations, genetics, pathogenesis and management of juvenile polyposis syndrome. PMID:22171123

  10. X-ray microprobe analysis of the retina and RPE in sheep with ovine ceroid-lipofuscinosis

    SciTech Connect

    Samuelson, D.A.; Armstrong, D.; Jolly, R. )

    1990-11-01

    Ovine ceroid-lipofuscinosis (OCL) is one animal model for the human condition, and because autofluorescent lipopigments are prominent in the brain and eye, it may also prove useful as a model for aging. For example, a progressive decline in electrical recording from brain and retina are observed in both aging and OCL. Samples of retinal and retinal pigment epithelial (RPE) tissues were obtained from a young control. 2 animals with OCL and a normal aged sheep. Specimens were cryo-fractured and examined by scanning electron microscopy/x-ray microanalysis. Measurements made of 6 individual cells in the ganglion layer of OCL specimens, the remainder of the retina, and RPE showed age-related changes in zinc, iron, and copper which were associated with lipopigment accumulation in the RPE. There was marked decrease in phosphate, sulfur, and manganese levels, as photoreceptor cells and their outer segments are lost in the disease process. This is the first report of metal analysis in the retina and RPE in a disease entity, and as a function of normal aging.

  11. Juvenile myoclonic epilepsy.

    PubMed

    Buchanan, N

    1995-08-01

    Juvenile myoclonic epilepsy is a relatively common, though under diagnosed, form of epilepsy that commences in adolescence. The distinguishing symptoms, diagnosis and medical management are discussed.

  12. Glycosylation, transport, and complex formation of palmitoyl protein thioesterase 1 (PPT1) – distinct characteristics in neurons

    PubMed Central

    Lyly, Annina; von Schantz, Carina; Salonen, Tarja; Kopra, Outi; Saarela, Jani; Jauhiainen, Matti; Kyttälä, Aija; Jalanko, Anu

    2007-01-01

    Background Neuronal ceroid lipofuscinoses (NCLs) are collectively the most common type of recessively inherited childhood encephalopathies. The most severe form of NCL, infantile neuronal ceroid lipofuscinosis (INCL), is caused by mutations in the CLN1 gene, resulting in a deficiency of the lysosomal enzyme, palmitoyl protein thioesterase 1 (PPT1). The deficiency of PPT1 causes a specific death of neocortical neurons by a mechanism, which is currently unclear. To understand the function of PPT1 in more detail, we have further analyzed the basic properties of the protein, especially focusing on possible differences in non-neuronal and neuronal cells. Results Our study shows that the N-glycosylation of N197 and N232, but not N212, is essential for PPT1's activity and intracellular transport. Deglycosylation of overexpressed PPT1 produced in neurons and fibroblasts demonstrates differentially modified PPT1 in different cell types. Furthermore, antibody internalization assays showed differences in PPT1 transport when compared with a thoroughly characterized lysosomal enzyme aspartylglucosaminidase (AGA), an important observation potentially influencing therapeutic strategies. PPT1 was also demonstrated to form oligomers by size-exclusion chromatography and co-immunoprecipitation assays. Finally, the consequences of disease mutations were analyzed in the perspective of our new results, suggesting that the mutations increase both the degree of glycosylation of PPT1 and its ability to form complexes. Conclusion Our current study describes novel properties for PPT1. We observe differences in PPT1 processing and trafficking in neuronal and non-neuronal cells, and describe for the first time the ability of PPT1 to form complexes. Understanding the basic characteristics of PPT1 is fundamental in order to clarify the molecular pathogenesis behind neurodegeneration in INCL. PMID:17565660

  13. Renewing Juvenile Justice

    ERIC Educational Resources Information Center

    Macallair, Daniel; Males, Mike; Enty, Dinky Manek; Vinakor, Natasha

    2011-01-01

    The Center on Juvenile and Criminal Justice (CJCJ) was commissioned by Sierra Health Foundation to critically examine California's juvenile justice system and consider the potential role of foundations in promoting systemic reform. The information gathered by CJCJ researchers for this report suggests that foundations can perform a key leadership…

  14. Juvenile Confinement in Context

    ERIC Educational Resources Information Center

    Mendel, Richard A.

    2012-01-01

    For more than a century, the predominant strategy for the treatment and punishment of serious and sometimes not-so-serious juvenile offenders in the United States has been placement into large juvenile corrections institutions, alternatively known as training schools, reformatories, or youth corrections centers. America's heavy reliance on…

  15. Juvenile Delinquency Intervention.

    ERIC Educational Resources Information Center

    Lipsey, Mark W.

    1988-01-01

    Three meta-analyses by C. J. Garrett (1984, 1985), P. Kaufman (1985), and W. S. Davidson and others (1984) of juvenile delinquency interventions are summarized. This systematic literature review indicates that interventions to reduce juvenile delinquency may have small, but meaningful, impacts. Promising avenues for future research are suggested.…

  16. Juvenile generalized pustular psoriasis.

    PubMed

    Xiao, Ting; Li, Bo; He, Chun-Di; Chen, Hong-Duo

    2007-08-01

    Generalized pustular psoriasis (GPP) is an erythrodermic, generalized form of pustular psoriasis. GPP is rare in children. The present study describes a case of juvenile GPP and reviews 12 juvenile GPP inpatients treated at our hospital in the period 1978-2005.

  17. Juvenile Rights. Second Edition.

    ERIC Educational Resources Information Center

    Eaneman, Paulette S.; And Others

    These classroom materials are part of the Project Benchmark series designed to teach secondary students about our legal concepts and systems. This unit focuses on juvenile rights and responsibilities under the law. The materials outline juvenile rights and responsibilities in the areas of parental control, education, free expression, search and…

  18. Distinguishing juvenile homicide from violent juvenile offending.

    PubMed

    DiCataldo, Frank; Everett, Meghan

    2008-04-01

    Juvenile homicide is a social problem that has remained a central focus within juvenile justice research in recent years. The term juvenile murderer describes a legal category, but it is purported to have significant scientific meaning. Research has attempted to conceptualize adolescent murderers as a clinical category that can be reliably distinguished from their nonhomicidal counterparts. This study examined 33 adolescents adjudicated delinquent or awaiting trial for murder and 38 adolescents who committed violent, nonhomicidal offenses to determine whether the two groups differed significantly on family history, early development, delinquency history, mental health, and weapon possession variables. The nonhomicide group proved more problematic on many of these measures. Two key factors did distinguish the homicide group: These adolescents endorsed the greater availability of guns and substance abuse at the time of their commitment offenses. The significance of this finding is discussed, and the implications for risk management and policy are reviewed.

  19. Juvenile Justice in California, 1983.

    ERIC Educational Resources Information Center

    California State Dept. of Justice, Sacramento. Bureau of Criminal Statistics and Special Services.

    This publication provides an overview of the processing of juvenile delinquency cases through the California juvenile justice system; provides information to aid administrators, planners, and researchers in the administration of juvenile justice; and maintains baseline data for further studies of the system. Information on juvenile arrests and…

  20. Juvenile Sex Offenders.

    PubMed

    Ryan, Eileen P; Otonichar, Joseph M

    2016-07-01

    Sexual offending by juveniles accounts for a sizable percentage of sexual offenses, especially against young children. In this article, recent research on female juvenile sex offenders (JSOs), risk factors for offending in juveniles, treatment, and the ways in which these youth may differ from general delinquents will be reviewed. Most JSOs do not go on to develop paraphilic disorders or to commit sex offenses during adulthood, and as a group, they are more similar to nonsexual offending juvenile delinquents than to adult sex offenders. Recent research has elucidated some differences between youth who commit sex offenses and general delinquents in the areas of atypical sexual interests, the use of pornography, and early sexual victimization during childhood.

  1. Juvenile Idiopathic Arthritis

    MedlinePlus

    ... rule out other conditions or infections, such as Lyme disease , that may cause similar symptoms or occur along ... ESR) Bones, Muscles, and Joints Evaluate Your Child's Lyme Disease Risk Word! Arthritis Arthritis Lupus Juvenile Idiopathic Arthritis ( ...

  2. Synaptic connections between layer 4 spiny neurone-layer 2/3 pyramidal cell pairs in juvenile rat barrel cortex: physiology and anatomy of interlaminar signalling within a cortical column.

    PubMed

    Feldmeyer, Dirk; Lübke, Joachim; Silver, R Angus; Sakmann, Bert

    2002-02-01

    Whole-cell voltage recordings were obtained from 64 synaptically coupled excitatory layer 4 (L4) spiny neurones and L2/3 pyramidal cells in acute slices of the somatosensory cortex ('barrel' cortex) of 17- to 23-days-old rats. Single action potentials (APs) in the L4 spiny neurone evoked single unitary EPSPs in the L2/3 pyramidal cell with a peak amplitude of 0.7 +/- 0.6 mV. The average latency was 2.1 +/- 0.6 ms, the rise time was 0.8 +/- 0.3 ms and the decay time constant was 12.7 +/- 3.5 ms. The percentage of failures of an AP in a L4 spiny neurone to evoke a unitary EPSP in the L2/3 pyramidal cell was 4.9 +/- 8.8 % and the coefficient of variation (c.v.) of the unitary EPSP amplitude was 0.27 +/- 0.13. Both c.v. and percentage of failures decreased with increased average EPSP amplitude. Postsynaptic glutamate receptors (GluRs) in L2/3 pyramidal cells were of the N-methyl-D-aspartate (NMDA) receptor (NMDAR) and the non-NMDAR type. At -60 mV in the presence of extracellular Mg2+ (1 mM), 29 +/- 15 % of the EPSP voltage-time integral was blocked by NMDAR antagonists. In 0 Mg2+, the NMDAR/AMPAR ratio of the EPSC was 0.50 +/- 0.29, about half the value obtained for L4 spiny neurone connections. Burst stimulation of L4 spiny neurones showed that EPSPs in L2/3 pyramidal cells depressed over a wide range of frequencies (1-100 s(-1) ). However, at higher frequencies (30 s(-1)) EPSP summation overcame synaptic depression so that the summed EPSP was larger than the first EPSP amplitude in the train. The number of putative synaptic contacts established by the axonal collaterals of the L4 projection neurone with the target neurone in layer 2/3 varied between 4 and 5, with an average of 4.5 +/- 0.5 (n = 13 pairs). Synapses were established on basal dendrites of the pyramidal cell. Their mean geometric distance from the pyramidal cell soma was 67 +/- 34 microm (range, 16-196 microm). The results suggest that each connected L4 spiny neurone produces a weak but reliable EPSP in

  3. Vocational Teachers' Role in Serving Juvenile Offenders.

    ERIC Educational Resources Information Center

    Meers, Gary D.

    1983-01-01

    Educators need to understand the juvenile justice system to understand what juvenile offenders go through while completing their sentences. This article reviews cases and juvenile charge classifications, and presents a model for alternative sentencing options for juveniles. (JOW)

  4. The paediatric rheumatologist and orphan disease - a story without happy ending.

    PubMed

    Roszkiewicz, Justyna; Biernacka-Zielińska, Małgorzata; Smolewska, Elżbieta

    2016-01-01

    Orphan diseases are not a common challenge in the everyday practice of the rheumatologist. Despite their extremely rare occurrence one of the patients under our care developed one of them - neuronal ceroid lipofuscinosis, the most frequent neurodegenerative disease observed in the paediatric population. We report a case of 2-year-old girl diagnosed with oligoarticular form of juvenile idiopathic arthritis treated in our Department with steroids and methotrexate and staying in the stage of disease remission. During routine checkups at Outpatient Clinic we observed progressive deterioration of girls neurological condition resulting in ataxia, gait disturbances with no rheumatological cause behind and speech impairment. The appearance of the symptoms was accompanied by frequent episodes of epileptic seizures, with little clinical improvement on combined antiepileptic treatment. Magnetic resonance imaging that we performed showed a picture highly suggestive of neuronal ceroid lipofuscinosis - atrophy of the patients cerebrum and cerebellum. Genetic testing conducted resulted in the diagnosis of late infantile neuronal ceroid lipofuscinosis (LINCL).

  5. Juvenile Incarceration and Health.

    PubMed

    Barnert, Elizabeth S; Perry, Raymond; Morris, Robert E

    2016-03-01

    Addressing the health status and needs of incarcerated youth represents an issue at the nexus of juvenile justice reform and health care reform. Incarcerated youth face disproportionately higher morbidity and higher mortality compared to the general adolescent population. Dental health, reproductive health, and mental health needs are particularly high, likely as a result of lower access to care, engagement in high-risk behaviors, and underlying health disparities. Violence exposure and injury also contribute to the health disparities seen in this population. Further, juvenile incarceration itself is an important determinant of health. Juvenile incarceration likely correlates with worse health and social functioning across the life course. Correctional health care facilities allow time for providers to address the unmet physical and mental health needs seen in this population. Yet substantial challenges to care delivery in detention facilities exist and quality of care in detention facilities varies widely. Community-based pediatricians can serve a vital role in ensuring continuity of care in the postdetention period and linking youth to services that can potentially prevent juvenile offending. Pediatricians who succeed in understanding and addressing the underlying social contexts of their patients' lives can have tremendous impact in improving the life trajectories of these vulnerable youth. Opportunities exist in clinical care, research, medical education, policy, and advocacy for pediatricians to lead change and improve the health status of youth involved in the juvenile justice system.

  6. Extending juvenility in grasses

    DOEpatents

    Kaeppler, Shawn; de Leon Gatti, Natalia; Foerster, Jillian

    2017-04-11

    The present invention relates to compositions and methods for modulating the juvenile to adult developmental growth transition in plants, such as grasses (e.g. maize). In particular, the invention provides methods for enhancing agronomic properties in plants by modulating expression of GRMZM2G362718, GRMZM2G096016, or homologs thereof. Modulation of expression of one or more additional genes which affect juvenile to adult developmental growth transition such as Glossy15 or Cg1, in conjunction with such modulation of expression is also contemplated. Nucleic acid constructs for down-regulation of GRMZM2G362718 and/or GRMZM2G096016 are also contemplated, as are transgenic plants and products produced there from, that demonstrate altered, such as extended juvenile growth, and display associated phenotypes such as enhanced yield, improved digestibility, and increased disease resistance. Plants described herein may be used, for example, as improved forage or feed crops or in biofuel production.

  7. Juvenile Sex Offenders.

    PubMed

    Ryan, Eileen P

    2016-01-01

    Public policy has tended to treat juvenile sex offenders (JSOs) as adult sex offenders in waiting, despite research that contradicts this notion. Although as a group, JSOs are more similar to general delinquents than to adult sex offenders, atypical sexual interests and sexual victimization during childhood may be a pathway for sexual offending that differentiates some JSOs from their nonsexually delinquent peers. Developmental considerations must be considered in risk assessment evaluations of these youth. This article reviews theories of sexual offending in youth, risk factors for juvenile offending and reoffending, psychopathology in JSOs, risk assessment, and treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Treating the Juvenile Offender

    ERIC Educational Resources Information Center

    Hoge, Robert D., Ed.; Guerra, Nancy G., Ed.; Boxer, Paul, Ed.

    2008-01-01

    This authoritative, highly readable reference and text is grounded in the latest knowledge on how antisocial and criminal behavior develops in youth and how it can effectively be treated. Contributors describe proven ways to reduce juvenile delinquency by targeting specific risk factors and strengthening young people's personal, family, and…

  9. What Is Juvenile Arthritis?

    MedlinePlus

    ... the possible causes of juvenile arthritis. They are studying genetic and environmental factors that they think are involved. They are also trying to improve current treatments and find new medicines that will work better with fewer side effects. Research supported by ...

  10. Juvenile Victimization and Delinquency.

    ERIC Educational Resources Information Center

    Esbensen, Finn-Aage; Huizinga, David

    1991-01-01

    Demographic characteristics of juvenile victims of crime and a potential relationship between victimization and self-reported delinquency are examined for 877 adolescents from a large midwestern city. Lifetime victimization rates (LVRs) are higher for those involved in delinquency, and LVRs rise with age and higher levels of delinquent behavior.…

  11. Treating the Juvenile Offender

    ERIC Educational Resources Information Center

    Hoge, Robert D., Ed.; Guerra, Nancy G., Ed.; Boxer, Paul, Ed.

    2008-01-01

    This authoritative, highly readable reference and text is grounded in the latest knowledge on how antisocial and criminal behavior develops in youth and how it can effectively be treated. Contributors describe proven ways to reduce juvenile delinquency by targeting specific risk factors and strengthening young people's personal, family, and…

  12. Juvenile Battens Disease.

    ERIC Educational Resources Information Center

    Gayton, Romayne

    1987-01-01

    Ten children diagnosed with juvenile Battens disease were tested over a three-year period in general intelligence, memory, listening and speech, motor skills, and general learning. Results showed that the patients followed a predetermined pattern but that the time span for development of memory, communication, and behavior problems varied greatly.…

  13. Silicon Neuron.

    DTIC Science & Technology

    Many researchers have developed neural architectures based on extremely simplified models of neurons . Recently, researchers have developed an analog...electronic model of a neuron that more accurately reproduces its biological counterpart. This electronic neuron was designed to emulate the ionic...currents present in biological neurons . Based on this neural model, we designed and fabricated an eight input neuron on a 2mm by 2mm 40 pin VLSI (very

  14. Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6

    PubMed Central

    Poët, Mallorie; Kornak, Uwe; Schweizer, Michaela; Zdebik, Anselm A.; Scheel, Olaf; Hoelter, Sabine; Wurst, Wolfgang; Schmitt, Anja; Fuhrmann, Jens C.; Planells-Cases, Rosa; Mole, Sara E.; Hübner, Christian A.; Jentsch, Thomas J.

    2006-01-01

    Mammalian CLC proteins function as Cl− channels or as electrogenic Cl−/H+ exchangers and are present in the plasma membrane and intracellular vesicles. We now show that the ClC-6 protein is almost exclusively expressed in neurons of the central and peripheral nervous systems, with a particularly high expression in dorsal root ganglia. ClC-6 colocalized with markers for late endosomes in neuronal cell bodies. The disruption of ClC-6 in mice reduced their pain sensitivity and caused moderate behavioral abnormalities. Neuronal tissues showed autofluorescence at initial axon segments. At these sites, electron microscopy revealed electron-dense storage material that caused a pathological enlargement of proximal axons. These deposits were positive for several lysosomal proteins and other marker proteins typical for neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. However, the lysosomal pH of Clcn6−/− neurons appeared normal. CLCN6 is a candidate gene for mild forms of human NCL. Analysis of 75 NCL patients identified ClC-6 amino acid exchanges in two patients but failed to prove a causative role of CLCN6 in that disease. PMID:16950870

  15. Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6.

    PubMed

    Poët, Mallorie; Kornak, Uwe; Schweizer, Michaela; Zdebik, Anselm A; Scheel, Olaf; Hoelter, Sabine; Wurst, Wolfgang; Schmitt, Anja; Fuhrmann, Jens C; Planells-Cases, Rosa; Mole, Sara E; Hübner, Christian A; Jentsch, Thomas J

    2006-09-12

    Mammalian CLC proteins function as Cl(-) channels or as electrogenic Cl(-)/H(+) exchangers and are present in the plasma membrane and intracellular vesicles. We now show that the ClC-6 protein is almost exclusively expressed in neurons of the central and peripheral nervous systems, with a particularly high expression in dorsal root ganglia. ClC-6 colocalized with markers for late endosomes in neuronal cell bodies. The disruption of ClC-6 in mice reduced their pain sensitivity and caused moderate behavioral abnormalities. Neuronal tissues showed autofluorescence at initial axon segments. At these sites, electron microscopy revealed electron-dense storage material that caused a pathological enlargement of proximal axons. These deposits were positive for several lysosomal proteins and other marker proteins typical for neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. However, the lysosomal pH of Clcn6(-/-) neurons appeared normal. CLCN6 is a candidate gene for mild forms of human NCL. Analysis of 75 NCL patients identified ClC-6 amino acid exchanges in two patients but failed to prove a causative role of CLCN6 in that disease.

  16. Juvenile offenders assessment.

    PubMed

    Folino, Jorge O; Mayer, Elizabeth L

    2011-09-01

    Evaluation of juveniles is an integral process that includes a broad bio-psycho-social clinical perspective together with the use of auxiliary instruments. The aim of this review is to report relevant issues for this process found in recent publications. Several evidences lead to broadening the assessment process of children and youngsters to include family functioning style. Mental health services allow the evaluation of multiple factors associated with antisocial behavior that may lead to devising preventive actions. In the Juvenile Justice System a wide-ranging evaluation must include the exploration of general personality characteristics and psychopathic traits in particular; attention deficit/hyperactivity disorder; intelligence; substance abuse and conduct disorder must be considered. A number of factors that have an impact on juvenile antisocial behavior have been identified and can be assessed using the appropriate methodology. The exploration of these factors at different developmental stages and in their various manifestations provide guidelines for devising preventive and therapeutic actions as well as for supporting judicial decisions. Though enriching the present state of the art is always a challenge, it is imperative to encourage the governments to utilize this knowledge to improve the care system of children and adolescents.

  17. Telepsychiatry in juvenile justice settings.

    PubMed

    Kaliebe, Kristopher E; Heneghan, James; Kim, Thomas J

    2011-01-01

    Telepsychiatry is emerging as a valuable means of providing mental health care in juvenile justice settings. Youth in the juvenile justice system have high levels of psychiatric morbidity. State and local juvenile justice systems frequently struggle to provide specialized psychiatric care, as these systems have limited resources and often operate in remote locations. Case studies in the use of telepsychiatry to provide improved care in juvenile corrections in 4 states are described, along with a review of advantages and disadvantages of telepsychiatry in these settings.

  18. Genetics Home Reference: juvenile idiopathic arthritis

    MedlinePlus

    ... Home Health Conditions juvenile idiopathic arthritis juvenile idiopathic arthritis Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Juvenile idiopathic arthritis refers to a group of conditions involving joint ...

  19. Genetics Home Reference: juvenile primary osteoporosis

    MedlinePlus

    ... Home Health Conditions juvenile primary osteoporosis juvenile primary osteoporosis Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Juvenile primary osteoporosis is a skeletal disorder characterized by thinning of ...

  20. Genetics Home Reference: juvenile myoclonic epilepsy

    MedlinePlus

    ... Home Health Conditions juvenile myoclonic epilepsy juvenile myoclonic epilepsy Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Juvenile myoclonic epilepsy is a condition characterized by recurrent seizures (epilepsy). ...

  1. Improving Literacy Skills of Juvenile Detainees. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Hodges, Jane; And Others

    The Office of Juvenile and Delinquency Prevention funded a model designed to improve the literacy level of youth in juvenile detention and correctional facilities. The model specified training language arts teachers and relevant staff and volunteers in direct instruction methods for rapid improvement of students' comprehension, particularly for…

  2. Juvenile Mentoring Program: A Progress Review. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Novotney, Laurence C.; Mertinko, Elizabeth; Lange, James; Baker, Tara Kelley

    The greatest support offered by the Office of Juvenile Justice and Delinquency Prevention for youth mentoring has been through the Juvenile Mentoring Program (JUMP), which provides one-to-one mentoring for youth at risk of delinquency, gang involvement, educational failure, or dropping out of school. Information on JUMP has been collected through…

  3. Juvenile Firesetting: A Research Overview. Juvenile Justice Bulletin

    ERIC Educational Resources Information Center

    Putnam, Charles T.; Kirkpatrick, John T.

    2005-01-01

    In 2002, the National Association of State Fire Marshals (NASFM) began developing applied research initiatives to help professionals curtail juvenile firesetting. The project included a review of the research literature, a conference of researchers and professionals involved in preventing juvenile firesetting, and a final report, upon which this…

  4. [Familial juvenile hyperuricemic nephropathy].

    PubMed

    Hummel, Aurélie

    2012-04-01

    Familial juvenile hyperuricemic nephropathy is a rare autosomal dominant disease. It is characterized by abnormal handling of urate responsible for hyperuricaemia often complicated of gouty arthritis. Renal failure is due to tubulointerstitial nephritis. Ultrasonography sometimes finds renal cysts of variable size and number. Renal histology, although not specific, shows interstitial fibrosis, atrophic tubules, sometimes enlarged and with irregular membrane thickening. Renal failure progresses to end stage between 30 and 60 years of age. Allopurinol treatment is recommended at the early stages of the disease, its efficacy on slowing down the progression of the disease is however not proven. There is genetic heterogeneity in familial juvenile hyperuricemic nephropathy. Uromodulin encoding Tamm-Horsfall protein is the only gene to date identified, responsible in less than half of the families. The described mutations most often concern a cystein and are clustering in exon 4. These mutations result in abnormal retention of the protein in endoplasmic reticulum of Henle loop cells and in reduction of its urinary excretion. The pathophysiology of the disease is however still dubious. Indeed, Tamm-Horsfall protein functions are not well known (anti-infectious role, cristallisation inhibition, immunomodulating role). Knock-out mice do not develop renal phenotype but are more prone to E. coli urinary infections. Uromodulin gene mutations have also been described in medullary cystic kidney disease, an autosomal dominant tubulointerstitial nephropathy, considered at first as a distinct disorder. Genetic progress allowed us to consider familial juvenile hyperuricemic nephropathy and medullary cystic kidney disease as the two facets of a same disease, we should call uromodulin associated kidney diseases. At least two other genes have been implicated in similar clinical presentation: TCF2 and the gene encoding renin.

  5. Pioneer glutamatergic cells develop into a morpho-functionally distinct population in the juvenile CA3 hippocampus

    PubMed Central

    Marissal, Thomas; Bonifazi, Paolo; Picardo, Michel Aimé; Nardou, Romain; Petit, Ludovic Franck; Baude, Agnès; Fishell, Gordon James; Ben-Ari, Yehezkel; Cossart, Rosa

    2012-01-01

    The developing CA3 hippocampus is comprised by highly connected hub neurons that are particularly effective in achieving network synchronization. Functional hub neurons were shown to be exclusively GABAergic, suggesting that the contribution of glutamatergic neurons to physiological synchronization processes at early postnatal stages is minimal. However, without fast GABAergic transmission, a different situation may prevail. In the adult CA3, blocking fast GABAergic transmission induces the generation of network bursts that can be triggered by the stimulation of single pyramidal neurons. Here we revisit the network function of CA3 glutamatergic neurons from a developmental viewpoint, without fast GABAergic transmission. We uncover a sub-population of early-generated glutamatergic neurons that impacts network dynamics when stimulated in the juvenile hippocampus. Additionally, this population displays characteristic morpho-physiological features in the juvenile and adult hippocampus. Therefore, the apparently homogeneous glutamatergic cell population likely displays a morpho-functional diversity rooted in temporal embryonic origins. PMID:23271650

  6. Pioneer glutamatergic cells develop into a morpho-functionally distinct population in the juvenile CA3 hippocampus.

    PubMed

    Marissal, Thomas; Bonifazi, Paolo; Picardo, Michel Aimé; Nardou, Romain; Petit, Ludovic Franck; Baude, Agnès; Fishell, Gordon James; Ben-Ari, Yehezkel; Cossart, Rosa

    2012-01-01

    The developing CA3 hippocampus is comprised by highly connected hub neurons that are particularly effective in achieving network synchronization. Functional hub neurons were shown to be exclusively GABAergic, suggesting that the contribution of glutamatergic neurons to physiological synchronization processes at early postnatal stages is minimal. However, without fast GABAergic transmission, a different situation may prevail. In the adult CA3, blocking fast GABAergic transmission induces the generation of network bursts that can be triggered by the stimulation of single pyramidal neurons. Here we revisit the network function of CA3 glutamatergic neurons from a developmental viewpoint, without fast GABAergic transmission. We uncover a sub-population of early-generated glutamatergic neurons that impacts network dynamics when stimulated in the juvenile hippocampus. Additionally, this population displays characteristic morpho-physiological features in the juvenile and adult hippocampus. Therefore, the apparently homogeneous glutamatergic cell population likely displays a morpho-functional diversity rooted in temporal embryonic origins.

  7. Juvenile Courts- Terms To Know.

    ERIC Educational Resources Information Center

    Update on Law-Related Education, 2000

    2000-01-01

    Offers a crossword puzzle that focuses on terms learned in this edition of "Update on Law-Related Education." Explains that the letters in the boxes spell the answer to this question: what do juvenile courts try to offer juveniles? Provides the clues and answers to the puzzle. (CMK)

  8. Iatrogenic Effect of Juvenile Justice

    ERIC Educational Resources Information Center

    Gatti, Uberto; Tremblay, Richard E.; Vitaro, Frank

    2009-01-01

    Background: The present study uses data from a community sample of 779 low-SES boys to investigate whether intervention by the juvenile justice system is determined, at least in part, by particular individual, familial and social conditions, and whether intervention by the juvenile courts during adolescence increases involvement in adult crime.…

  9. Juvenile Justice in Rural America.

    ERIC Educational Resources Information Center

    Jankovic, Joanne, Ed.; And Others

    Producing a much-needed organized body of literature about rural juvenile justice, 14 papers (largely from the 1979 National Symposium on Rural Justice) are organized to identify current issues, identify forces causing changes in current systems, review programs responding to rural juvenile justice problems, and provide planning models to aid…

  10. Juvenile Crime. Opposing Viewpoints Series.

    ERIC Educational Resources Information Center

    Sadler, A. E., Ed.

    Books in the Opposing Viewpoints Series present debates about current issues that can be used to teach critical reading and thinking skills. The variety of opinions expressed in this collection of articles and book excerpts explores many aspects of juvenile crime. It is a commonly held view that the number of crimes committed by juveniles is…

  11. Psychopathology in Female Juvenile Offenders

    ERIC Educational Resources Information Center

    Dixon, Angela; Howie, Pauline; Starling, Jean

    2004-01-01

    Background: The aim was to document the spectrum of present and lifetime psychological disorders in female juvenile offenders, and to examine the relations between mental health status and socio-demographic, family and trauma variables. Method: One hundred juvenile offenders were matched with a comparison group of 100 females on age and…

  12. Iatrogenic Effect of Juvenile Justice

    ERIC Educational Resources Information Center

    Gatti, Uberto; Tremblay, Richard E.; Vitaro, Frank

    2009-01-01

    Background: The present study uses data from a community sample of 779 low-SES boys to investigate whether intervention by the juvenile justice system is determined, at least in part, by particular individual, familial and social conditions, and whether intervention by the juvenile courts during adolescence increases involvement in adult crime.…

  13. Suicide Prevention in Juvenile Facilities.

    ERIC Educational Resources Information Center

    Hayes, Lindsay M.

    2000-01-01

    Youth suicide is recognized as a serious public health problem, but suicide within juvenile facilities has not received comparable attention, and the extent and nature of these deaths remain unknown. This article utilizes an example of a young man in a juvenile justice facility who succeeded in committing suicide to illustrate these points.…

  14. Mental Illness and Juvenile Offenders

    PubMed Central

    Underwood, Lee A.; Washington, Aryssa

    2016-01-01

    Within the past decade, reliance on the juvenile justice system to meet the needs of juvenile offenders with mental health concerns has increased. Due to this tendency, research has been conducted on the effectiveness of various intervention and treatment programs/approaches with varied success. Recent literature suggests that because of interrelated problems involved for youth in the juvenile justice system with mental health issues, a dynamic system of care that extends beyond mere treatment within the juvenile justice system is the most promising. The authors provide a brief overview of the extent to which delinquency and mental illness co-occur; why treatment for these individuals requires a system of care; intervention models; and the juvenile justice systems role in providing mental health services to delinquent youth. Current and future advancements and implications for practitioners are provided. PMID:26901213

  15. Mental Illness and Juvenile Offenders.

    PubMed

    Underwood, Lee A; Washington, Aryssa

    2016-02-18

    Within the past decade, reliance on the juvenile justice system to meet the needs of juvenile offenders with mental health concerns has increased. Due to this tendency, research has been conducted on the effectiveness of various intervention and treatment programs/approaches with varied success. Recent literature suggests that because of interrelated problems involved for youth in the juvenile justice system with mental health issues, a dynamic system of care that extends beyond mere treatment within the juvenile justice system is the most promising. The authors provide a brief overview of the extent to which delinquency and mental illness co-occur; why treatment for these individuals requires a system of care; intervention models; and the juvenile justice systems role in providing mental health services to delinquent youth. Current and future advancements and implications for practitioners are provided.

  16. Juvenile 'Perinasal' Angiofibroma.

    PubMed

    Mishra, Anupam; Verma, Veerendra; Mishra, Subhash Chandra

    2017-03-01

    The extranasopharyngeal angiofibroma is a separate clinical entity but those involving infratemporal fossa and cheek resemble juvenile nasopharyngeal angiofibroma (JNA) and hence have been labelled as juvenile perinasal angiofibroma (JPA) in this paper. This paper presents a 7th case of JPA and attempts to review the world literature on JPA, along with a proposal of staging the disease. A 16 year male presented with a painless compressible facial swelling since 7 months without any epistaxis or nasal obstruction. Initially a vascular lesion was suspected but JNA without nasal extension was strongly suspected on imaging. A deep trucut biopsy confirmed the histopathology. The vascular enhancement was significant and the tumour was excised through open approach (Weber Fergusson). JPA that can be regarded as a variant of JNA that fails to extend medially. Imaging demonstrates classical JNA findings with a clear nose/nasopharynx. A deep trucut biopsy under control in inpatient settings may sometimes help. JPA presents most commonly in Stage II where an open facial approach preferably following selective preoperative embolization is indicated. Hence with painless compressible (or non-compressible) cheek swelling suspected to be of a vascular etiology, a high degree of clinical suspicion for JPA needs to maintained in order to prevent a misdiagnosis.

  17. Recruitment and replacement of hippocampal neurons in young and adult chickadees: an addition to the theory of hippocampal learning.

    PubMed Central

    Barnea, A; Nottebohm, F

    1996-01-01

    We used [3H]thymidine to document the birth of neurons and their recruitment into the hippocampal complex (HC) of juvenile (4.5 months old) and adult blackcapped chickadees (Parus atricapillus) living in their natural surroundings. Birds received a single dose of [3H]thymidine in August and were recaptured and killed 6 weeks later, in early October. All brains were stained with Cresyl violet, a Nissl stain. The boundaries of the HC were defined by reference to the ventricular wall, the brain surface, or differences in neuronal packing density. The HC of juveniles was as large as or larger than that of adults and packing density of HC neurons was 31% higher in juveniles than in adults. Almost all of the 3H-labeled HC neurons were found in a 350-m-wide layer of tissue adjacent to the lateral ventricle. Within this layer the fraction of 3H-labeled neurons was 50% higher in juveniles than in adults. We conclude that the HC of juvenile chickadees recruits more neurons and has more neurons than that of adults. We speculate that juveniles encounter greater environmental novelty than adults and that the greater number of HC neurons found in juveniles allows them to learn more than adults. At a more general level, we suggest that (i) long-term learning alters HC neurons irreversibly; (ii) sustained hippocampal learning requires the periodic replacement of HC neurons; (iii) memories coded by hippocampal neurons are transferred elsewhere before the neurons are replaced. Images Fig. 1 Fig. 2 PMID:11607626

  18. Juvenile justice mental health services.

    PubMed

    Thomas, Christopher R; Penn, Joseph V

    2002-10-01

    As the second century of partnership begins, child psychiatry and juvenile justice face continuing challenges in meeting the mental health needs of delinquents. The modern juvenile justice system is marked by a significantly higher volume of cases, with increasingly complicated multiproblem youths and families with comorbid medical, psychiatric, substance abuse disorders, multiple family and psychosocial adversities, and shrinking community resources and alternatives to confinement. The family court is faced with shrinking financial resources to support court-ordered placement and treatment programs in efforts to treat and rehabilitate youths. The recognition of high rates of mental disorders for incarcerated youth has prompted several recommendations for improvement and calls for reform [56,57]. In their 2000 annual report, the Coalition for Juvenile Justice advocated increased access to mental health services that provide a continuum of care tailored to the specific problems of incarcerated youth [58]. The specific recommendations of the report for mental health providers include the need for wraparound services, improved planning and coordination between agencies, and further research. The Department of Justice, Office of Juvenile Justice and Delinquency Prevention has set three priorities in dealing with the mental health needs of delinquents: further research on the prevalence of mental illness among juvenile offenders, development of mental health screening assessment protocols, and improved mental health services [59]. Other programs have called for earlier detection and diversion of troubled youth from juvenile justice to mental health systems [31,56]. Most recently, many juvenile and family courts have developed innovative programs to address specific problems such as truancy or substance use and diversionary or alternative sentencing programs to deal with first-time or nonviolent delinquents. All youths who come in contact with the juvenile justice system

  19. Miranda Rights: Implications for Juveniles with Disabilities

    ERIC Educational Resources Information Center

    Katsiyannis, Antonis; Barrett, David E.; Losinski, Mickey L.

    2011-01-01

    Juvenile delinquency in the United States has been a persistent concern for decades. Consequently, because more juveniles have been referred to juvenile court and the arrest rate of preteen offenders has increased to almost three times that of older youth, the persistent and often controversial issue of the capacity of juvenile offenders to waive…

  20. Miranda Rights: Implications for Juveniles with Disabilities

    ERIC Educational Resources Information Center

    Katsiyannis, Antonis; Barrett, David E.; Losinski, Mickey L.

    2011-01-01

    Juvenile delinquency in the United States has been a persistent concern for decades. Consequently, because more juveniles have been referred to juvenile court and the arrest rate of preteen offenders has increased to almost three times that of older youth, the persistent and often controversial issue of the capacity of juvenile offenders to waive…

  1. Juvenile obesity enhances emotional memory and amygdala plasticity through glucocorticoids.

    PubMed

    Boitard, Chloé; Maroun, Mouna; Tantot, Frédéric; Cavaroc, Amandine; Sauvant, Julie; Marchand, Alain; Layé, Sophie; Capuron, Lucile; Darnaudery, Muriel; Castanon, Nathalie; Coutureau, Etienne; Vouimba, Rose-Marie; Ferreira, Guillaume

    2015-03-04

    In addition to metabolic and cardiovascular disorders, obesity is associated with adverse cognitive and emotional outcomes. Its growing prevalence during adolescence is particularly alarming since recent evidence indicates that obesity can affect hippocampal function during this developmental period. Adolescence is a decisive period for maturation of the amygdala and the hypothalamic-pituitary-adrenal (HPA) stress axis, both required for lifelong cognitive and emotional processing. However, little data are available on the impact of obesity during adolescence on amygdala function. Herein, we therefore evaluate in rats whether juvenile high-fat diet (HFD)-induced obesity alters amygdala-dependent emotional memory and whether it depends on HPA axis deregulation. Exposure to HFD from weaning to adulthood, i.e., covering adolescence, enhances long-term emotional memories as assessed by odor-malaise and tone-shock associations. Juvenile HFD also enhances emotion-induced neuronal activation of the basolateral complex of the amygdala (BLA), which correlates with protracted plasma corticosterone release. HFD exposure restricted to adulthood does not modify all these parameters, indicating adolescence is a vulnerable period to the effects of HFD-induced obesity. Finally, exaggerated emotional memory and BLA synaptic plasticity after juvenile HFD are alleviated by a glucocorticoid receptor antagonist. Altogether, our results demonstrate that juvenile HFD alters HPA axis reactivity leading to an enhancement of amygdala-dependent synaptic and memory processes. Adolescence represents a period of increased susceptibility to the effects of diet-induced obesity on amygdala function.

  2. Juvenile onset Huntington's disease--clinical and research perspectives.

    PubMed

    Nance, M A; Myers, R H

    2001-01-01

    Huntington's disease (HD) is an inherited neurodegenerative disorder. The mutation which causes the disease is an expansion in the number of repetitions of three nucleotides, C, A, and G in exon 1 of the huntingtin gene. The gene normally has 15 to 30 repeats and an expansion to 40 or more is associated with HD. HD usually has a mid-life onset, but a juvenile form, defined by onset of symptoms before the age of 21 years, is present in about 7% of HD cases. Juvenile HD is characterized by (1) transmission from an HD affected father, (2) an unusually large repeat size, usually of 60 or more units, and (3) unique clinical features, including rigidity and seizure disorder. Although juvenile onset is associated with a more severe neuropathological involvement, the neuropathological characteristics of juvenile HD are similar to those seen in the adult form in that the striatum bears the brunt of the illness. Clumps of protein, termed inclusion bodies, which stain positive for huntingtin and ubiquitin, are found primarily in the nucleus but also in the cytoplasm and axons in HD neurons. Research suggests that these inclusion bodies sequester a deleterious protein fragment and prolong cell life during the degenerative process of the disease.

  3. Autosomal dominant juvenile recurrent parotitis.

    PubMed Central

    Reid, E; Douglas, F; Crow, Y; Hollman, A; Gibson, J

    1998-01-01

    Juvenile recurrent parotitis is a common cause of inflammatory salivary gland swelling in children. A variety of aetiological factors has been proposed for the condition. Here we present a family where four members had juvenile recurrent parotitis and where two other family members may have had an atypical form of the condition. The segregation pattern in the family is consistent with autosomal dominant inheritance with incomplete penetrance and this suggests that, at least in some cases, genetic factors may be implicated in juvenile recurrent parotitis. PMID:9610807

  4. [JUVENILE DERMATOMYOSITIS AND CALCINOSIS].

    PubMed

    Zhvania, M

    2015-01-01

    Juvenile Dermatomiositis (JD) is autoimmune disease that progresses with time; JD's main differentiated syndromes are rash on the skin, poor function of muscles, and often developing invalidism. If the health practitioners manage to diagnose the JD on an early stage and prescribe the adequate treatment the disease will not progress aggressively. This approach is tangible for practical rheumatology and pediatric. The article aims to present the reasons of the development of the JD and calcinosis. The study based on the description of the patients with JD. There are distinguished the main symptoms of the disease in children: frequent and acute developments of muscles calcinosis, occasionally with diffuse character followed with hypotrophy of the muscles, contractures and invalidism. One of the patient cases that describe the article is the thirteen-year boy with JD indicating repeated sequence of the disease, with diffusive calcinosis, cellulitis followed with secondary infection and impaired vision.

  5. Juvenile nasopharyngeal angiofibroma

    PubMed Central

    Makhasana, Jashika Adil Shroff; Kulkarni, Meena A; Vaze, Suhas; Shroff, Adil Sarosh

    2016-01-01

    Juvenile nasopharyngeal angiofibroma (JNA) is a rare benign tumor arising predominantly in the nasopharynx of adolescent males. It is an aggressive neoplasm and shows a propensity for destructive local spread often extending to the base of the skull and into the cranium. Clinically, however, it is obscure with painless, progressive unilateral nasal obstruction being the common presenting symptom with or without epistaxis and rhinorrhea. Diagnosis of JNA is made by complete history, clinical examination, radiography, nasal endoscopy and by using specialized imaging techniques such as arteriography, computer tomography and magnetic resonance imaging. Histopathology reveals a fibrocellular stroma with spindle cells and haphazard arrangement of collagen interspersed with an irregular vascular pattern. A case report of JNA with rare intra-oral manifestation in a 17-year-old male patient is presented in the article. JNA being an aggressive tumor may recur posttreatment. Thus, early diagnosis, accurate staging, and adequate treatment are essential in the management of this lesion. PMID:27601836

  6. Juvenile idiopathic arthritis.

    PubMed

    Bhatt, Krupa H; Karjodkar, Freny R; Sansare, Kaustubh; Patil, Darshana

    2014-01-01

    Juvenile Idiopathic Arthritis (JIA) is the most chronic musculoskeletal disease of pediatric population. The chronic course of disease has a great impact on oral health. Temporomandibular joint is involved in JIA causing limited mouth opening with progressive open bite, retrognathia, microgenia and bird like appearance. Joints of upper and lower extremities are also involved. Effect on upper limb function leads to difficulty with fine motor movements required for brushing and flossing. This increases incidence of caries and periodontal disease in children. The cause of JIA is still poorly understood and none of the available drugs for JIA can cure the disease. However, prognosis has improved as a result of progress in disease classification and management. The dental practitioner should be familiar with the symptoms and oral manifestations of JIA to help manage as multidisciplinary management is essential.

  7. Juvenile chronic arthritis.

    PubMed

    Southwood, T R; Woo, P

    1995-05-01

    The nomenclature and classification criteria for arthritis in children should be dealt with initially as separate issues, although they are undoubtedly intertwined. The classification criteria should aim to delineate homogeneous patient populations, yet should be flexible enough to incorporate advances in disease knowledge. It should be recognized that arriving at an international consensus for classification criteria will merely provide a set of operational definitions to facilitate research, and not a set of diagnostic criteria. Indeed the only point to obtaining consensus is to begin a process of systematic ongoing review of the criteria. The labels attached to any of these diseases should facilitate accurate communication. In view of the heterogeneous nature of childhood arthritis, consideration should be given to using a broad umbrella term such as juvenile or childhood arthritis only for communicating with the lay public. Medical nomenclature should be formulated to reflect accurately homogeneous subgroups of arthritis, and should not artificially proscribe a relationship between paediatric and adult disease.

  8. [Juvenile idiopathic systemic arthritis].

    PubMed

    Baksiene, Dalia; Kasparaviciene, Jūrate; Zebiene, Migla; Puteliene, Brigita

    2003-01-01

    THE PURPOSE OF THE STUDY was to evaluate the peculiarities of the clinical features, laboratory parameters and tactics of treatment in juvenile idiopatic systematic arthritis. A retrospective data review of 41 children (26 boys and 15 girls) who underwent treatment for systemic arthritis (according to ILAR criteria) in our institution between 1992 and 2002 was performed. The disease started with fever of unknown origin in all cases. In 73% of patients it lasted longer than one month, in 54% fever was with twice daily spikers in the morning and in the evening. The rash during the rise of temperature appeared in 49%, in most cases (70%) there was a maculo-papular rash. Lymphadenopathy and serositis were observed in 32%, hepatomegaly in 29%, and splenomegaly in 24%. Arthritis coincided with the fever in 29% of patients, in majority of cases it was progressing to a severe persistent arthritis after the systematic phase. There was no specific laboratory findings: neutrophilic leucocytosis was found in 73%, anemia - in 80.5%, trombocytosis - in 36.6%, elevated CRP - in 63.4%, dysproteinemia - in 79% of patients. Antinuclear factors were absent in all examined children. For all patients intravenous methylprednisolone pulses have been administered (10-22 mg/kg/infusion). Prednisolone was also continued orally (1-2 mg/kg/day). 24.4% of patients required in addition immunosupressive agents such as methotrexate, azathioprine and cyclophosphamide. Puls-therapy of methylprednisolone is a safe and sufficiently effective method of treatment in most cases of the systematic juvenile arthritis.

  9. Juvenile homosexual homicide.

    PubMed

    Myers, Wade C; Chan, Heng Choon Oliver

    2012-01-01

    Limited information exists on juvenile homosexual homicide (JHH), that is, youths who perpetrate sexual homicides against same-sex victims. Only a handful of cases from the United States and internationally have been described in the literature. This study, the first of its kind, examines the epidemiology, victimology, victim-offender relationship, and weapon-use patterns in JHH offenders using a large U.S. database on homicide spanning three decades. The data for this study were derived from the Federal Bureau of Investigation's Supplementary Homicide Reports (SHRs) for the years 1976 through 2005. A total of 93 cases of JHH were identified. On average, three of these crimes occurred annually in the U.S., and there was a marked decline in its incidence over the study period. Ninety-five percent were male offender-male victim cases and 5% were female offender-female victim cases. JHH offenders were over-represented amongst all juvenile sexual murderers, similar to their adult counterparts. The majority of these boys were aged 16 or 17 and killed adult victims. They were significantly more likely to kill adult victims than other age groups, to be friends or acquaintances of the victims, and to use contact/edged weapons or firearms. Most offenders killed same-race victims, although Black offenders were significantly more likely than White offenders to kill interracially. A case report is provided to illustrate JHH. Further research is needed to promote our understanding of the pathogenesis, etiology, and associated risk factors for this aberrant form of murder by children. Copyright © 2012 John Wiley & Sons, Ltd.

  10. [Neuronal ageing].

    PubMed

    Piechota, Małgorzata; Sunderland, Piotr

    2014-01-01

    Ageing leads to irreversible alterations in the nervous system, which to various extent impair its functions such as capacity to learn and memory. In old neurons and brain, similarly to what may take place in other cells, there is increased oxidative stress, disturbed energetic homeostasis and metabolism, accumulation of damage in proteins and nucleic acids. Characteristic of old neurons are alterations in plasticity, synaptic transmission, sensitivity to neurotrophic factors and cytoskeletal changes. Some markers of senescence, whose one of them is SA-beta-galactosidase were used to show the process of neuronal ageing both in vitro, and in vivo. Some research suggest that, despite the fact that neurons are postmitotic cells, it is cell cycle proteins which play a certain role in their biology, e.g. differentiation. However, their role in neuronal ageing is not known or explained. Ageing is the serious factor of development of neurodegenerative diseases among others Alzheimer disease.

  11. Magnetic resonance findings of the corpus callosum in canine and feline lysosomal storage diseases.

    PubMed

    Hasegawa, Daisuke; Tamura, Shinji; Nakamoto, Yuya; Matsuki, Naoaki; Takahashi, Kimimasa; Fujita, Michio; Uchida, Kazuyuki; Yamato, Osamu

    2013-01-01

    Several reports have described magnetic resonance (MR) findings in canine and feline lysosomal storage diseases such as gangliosidoses and neuronal ceroid lipofuscinosis. Although most of those studies described the signal intensities of white matter in the cerebrum, findings of the corpus callosum were not described in detail. A retrospective study was conducted on MR findings of the corpus callosum as well as the rostral commissure and the fornix in 18 cases of canine and feline lysosomal storage diseases. This included 6 Shiba Inu dogs and 2 domestic shorthair cats with GM1 gangliosidosis; 2 domestic shorthair cats, 2 familial toy poodles, and a golden retriever with GM2 gangliosidosis; and 2 border collies and 3 chihuahuas with neuronal ceroid lipofuscinoses, to determine whether changes of the corpus callosum is an imaging indicator of those diseases. The corpus callosum and the rostral commissure were difficult to recognize in all cases of juvenile-onset gangliosidoses (GM1 gangliosidosis in Shiba Inu dogs and domestic shorthair cats and GM2 gangliosidosis in domestic shorthair cats) and GM2 gangliosidosis in toy poodles with late juvenile-onset. In contrast, the corpus callosum and the rostral commissure were confirmed in cases of GM2 gangliosidosis in a golden retriever and canine neuronal ceroid lipofuscinoses with late juvenile- to early adult-onset, but were extremely thin. Abnormal findings of the corpus callosum on midline sagittal images may be a useful imaging indicator for suspecting lysosomal storage diseases, especially hypoplasia (underdevelopment) of the corpus callosum in juvenile-onset gangliosidoses.

  12. Juvenile onset spondyloarthropathies: therapeutic aspects

    PubMed Central

    Burgos-Vargas, R

    2002-01-01

    Juvenile onset spondyloarthropathy (SpA) is a term that refers to a group of human leucocyte antigen (HLA)-B27 associated inflammatory disorders affecting children under the age of 16 years, producing a continuum of clinical symptoms through adulthood. This disease is characterised by enthesopathy and arthropathy affecting the joints of the lower extremities and seronegativity for IgM rheumatoid factor and antinuclear antibodies. Children usually present with undifferentiated SpA and progress to differentiated forms over time. Except for the prevalence of some clinical features at onset, the pathogenic and clinical aspects of juvenile onset SpAs resemble those of the adult disease. Thus application of the same or similar therapeutic measures for both juvenile and adult onset SpAs seems logical. Current treatments for juvenile onset SpA provide symptomatic improvement, but do not alter disease progression. The increased expression of tumour necrosis factor alpha (TNFα) in synovial tissue of patients with adult and juvenile onset SpA and its correlation with infiltration of inflammatory mediators into the synovia suggest a significant pathogenic role of this cytokine. Clinical trials of anti-TNFα antibody (infliximab) therapy in patients with adult onset SpA have demonstrated significant clinical improvement in inflammatory pain, function, disease activity, and quality of life in correlation with histological and immunohistochemical evidence of modulation of synovial inflammatory processes. These promising findings suggest that anti-TNFα therapy may confer similar benefits in patients with juvenile onset SpA. PMID:12381509

  13. Adaptive plasticity in the auditory thalamus of juvenile barn owls.

    PubMed

    Miller, Greg L; Knudsen, Eric I

    2003-02-01

    Little is known about the capacity of the thalamus for experience-dependent plasticity. Here, we demonstrate adaptive changes in the tuning of auditory thalamic neurons to a major category of sound localization cue, interaural time differences (ITDs), in juvenile barn owls that experience chronic abnormal hearing. Abnormal hearing was caused by a passive acoustic filtering device implanted in one ear that altered the timing and level of sound differently at different frequencies. Experience with this device resulted in adaptive, frequency-dependent shifts in the tuning of thalamic neurons to ITD that mimicked the acoustic effects of the device. Abnormal hearing did not alter ITD tuning in the central nucleus of the inferior colliculus, the primary source of input to the auditory thalamus. Therefore, the thalamus is the earliest stage in the forebrain pathway in which this plasticity is expressed. A visual manipulation, chronic prismatic displacement of the visual field, which causes adaptive changes in ITD tuning at higher levels in the forebrain, had no effect on thalamic ITD tuning. The results demonstrate that, during the juvenile period, auditory experience shapes neuronal response properties in the thalamus in a frequency-specific manner and suggest that this thalamic plasticity is driven by self-organizational forces and not by visual instruction.

  14. Managing juvenile Huntington's disease.

    PubMed

    Quarrell, Oliver W J; Nance, Martha A; Nopoulos, Peggy; Paulsen, Jane S; Smith, Jonathan A; Squitieri, Ferdinando

    2013-06-01

    Huntington's disease (HD) is a well-recognized progressive neurodegenerative disorder that follows an autosomal dominant pattern of inheritance. Onset is insidious and can occur at almost any age, but most commonly the diagnosis is made between the ages of 35 and 55 years. Onset ≤20 years of age is classified as juvenile HD (JHD). This age-based definition is arbitrary but remains convenient. There is overlap between the clinical pathological and genetic features seen in JHD and more traditional adult-onset HD. Nonetheless, the frequent predominance of bradykinesia and dystonia early in the course of the illness, more frequent occurrence of epilepsy and myoclonus, more widespread pathology, and larger genetic lesion means that the distinction is still relevant. In addition, the relative rarity of JHD means that the clinician managing the patient is often doing so for the first time. Management is, at best, symptomatic and supportive with few or no evidence-based guidelines. In this article, the authors will review what is known of the condition and present some suggestions based on their experience.

  15. Encoding of sound envelope transients in the auditory cortex of juvenile rats and adult rats.

    PubMed

    Lu, Qi; Jiang, Cuiping; Zhang, Jiping

    2016-02-01

    Accurate neural processing of time-varying sound amplitude and spectral information is vital for species-specific communication. During postnatal development, cortical processing of sound frequency undergoes progressive refinement; however, it is not clear whether cortical processing of sound envelope transients also undergoes age-related changes. We determined the dependence of neural response strength and first-spike latency on sound rise-fall time across sound levels in the primary auditory cortex (A1) of juvenile (P20-P30) rats and adult (8-10 weeks) rats. A1 neurons were categorized as "all-pass", "short-pass", or "mixed" ("all-pass" at high sound levels to "short-pass" at lower sound levels) based on the normalized response strength vs. rise-fall time functions across sound levels. The proportions of A1 neurons within each of the three categories in juvenile rats were similar to that in adult rats. In general, with increasing rise-fall time, the average response strength decreased and the average first-spike latency increased in A1 neurons of both groups. At a given sound level and rise-fall time, the average normalized neural response strength did not differ significantly between the two age groups. However, the A1 neurons in juvenile rats showed greater absolute response strength, longer first-spike latency compared to those in adult rats. In addition, at a constant sound level, the average first-spike latency of juvenile A1 neurons was more sensitive to changes in rise-fall time. Our results demonstrate the dependence of the responses of rat A1 neurons on sound rise-fall time, and suggest that the response latency exhibit some age-related changes in cortical representation of sound envelope rise time.

  16. Juveniles tried as adults: the age of the juvenile matters.

    PubMed

    Semple, Jaclyn K; Woody, William Douglas

    2011-08-01

    Serious juvenile crimes require evaluation of a child as a criminal defendant in adult court. In such cases, it is crucial to understand jurors' attitudes, biases, and ability to follow legal instructions and maintain fairness. 308 undergraduate psychology students served as mock jurors, were randomly separated into four groups, and each group read the same realistic summary of a trial with the defendant's age presented as 13, 15, 17, or 21 years. Participants were asked to render guilty or not guilty verdicts and, if guilty, to suggest sentences. Chi-squared analysis indicated 13- and 15-year-old defendants were convicted less often than 17- and 21-year-old defendants, showing that jurors distinguished between juvenile defendants of different ages, but not minors and adults as defined by law. Additional analysis showed that age did not affect sentencing recommendations. Decision processes jurors use for juveniles tried as adults are discussed.

  17. Forensic aspects of juvenile violence.

    PubMed

    Haller, L H

    2000-10-01

    The juvenile justice system was created because it was recognized that youthful offenders needed to be managed differently from adults. They were to receive habilitation services instead of punishment. It is now more than a century since the creation of the first juvenile court. After 67 years, the US Supreme Court, in Kent v United States stated that the model was not working because juveniles in the criminal justice system received no treatment and they had no rights. Because the issue that had been appealed was the lack of rights (not lack of treatment), the Court mandated that juveniles, like adults, be given certain rights. The following year, in In re Gault, the Court expanded these rights. Subsequent Supreme Court cases have dealt with these kinds of issues--that is, whether juvenile offenders are entitled to the same rights as adults and subject to the same penalties. The Supreme Court has never heard a "right to treatment" case, which is the other part of the juvenile court system. Cases have been brought in lower courts (e.g., Nelson v. Heyne, 1972) alleging inadequate treatment services, but no national impact has resulted. Thus, in general, children in the juvenile court system do not have an enforceable right to treatment and can obtain only what services are available in their jurisdictions. The services often are woefully inadequate. Sentencing a youth to probation, with the requirement that he or she participate in counseling or mental health treatment, is meaningless if services are not available. Community-based, model programs that provide effective treatment do exist. They are, as yet, the rare exception rather than the norm and, therefore, are not available to most youthful offenders. Incarcerated juveniles, obviously, cannot avail themselves of community programs. Litigation to give these youth the same rights as adults in penal institutions is not the answer because incarcerated adults don't have a right to treatment, only a right to be free

  18. Genetics Home Reference: juvenile polyposis syndrome

    MedlinePlus

    ... and symptoms of the disorder. Juvenile polyposis of infancy is characterized by polyps that occur throughout the gastrointestinal tract during infancy. Juvenile polyposis of infancy is the most severe ...

  19. Recidivism of juvenile homicide offenders.

    PubMed

    Vries, Anne M; Liem, Marieke

    2011-01-01

    Serious offenses against persons perpetrated by juveniles raise fundamental questions about the background, causes, and prevention of future crime. The current study addresses the potential of future crime of all juvenile homicide offenders (JHOs) in the Netherlands in the period 1992-2007. In contrast to former research on recidivism of JHOs, which has been merely descriptive, the present study integrates theoretical perspectives as to why some of these juveniles turn back to crime, while others do not. To this end, relationships are investigated between recidivism behavior and risk factors. Results indicate that male JHOs, and JHOs who maintain relationships with delinquents, run a greater risk of reoffending. Copyright © 2011 John Wiley & Sons, Ltd.

  20. Comparative bacteriology of juvenile periodontitis.

    PubMed Central

    Moore, W E; Holdeman, L V; Cato, E P; Smibert, R M; Burmeister, J A; Palcanis, K G; Ranney, R R

    1985-01-01

    Statistical comparisons of the floras associated with juvenile periodontitis, severe periodontitis, and moderate periodontitis indicated that differences in the bacterial compositions of affected sites in these populations were not statistically significant. The subgingival flora of affected juvenile periodontitis sites was statistically significantly different from the adjacent supragingival flora and from the subgingival floras of people with healthy gingiva and of children with developing (experimental) gingivitis. However, the subgingival flora of affected juvenile periodontitis sites was not significantly different from the flora of sites with gingival index scores of 1 or 2 in adults with developing (experimental) gingivitis. Of 357 bacterial taxa among over 18,000 isolates, 54 non-treponemal species, 2 treponemal species, and mycoplasma were most associated with diseased periodontal sulci. These species comprised an increasing proportion of the flora during developing gingivitis and constituted over half of the cultivable flora of diseased sites. PMID:3988344

  1. Core decompression for juvenile osteonecrosis.

    PubMed

    Herrera-Soto, José A; Price, Charles T

    2011-07-01

    Core decompression may be used as adjunct for treatment in some cases of Legg-Calvé-Perthes disease (LCPD). The primary application is for patients with onset at 12 years of age or older. We recommend classifying these older patients as idiopathic juvenile osteonecrosis and treating them similarly to adults with avascular necrosis. Juvenile osteonecrosis may benefit from core decompression combined with shelf acetabuloplasty during the early stages of necrosis. Younger children with LCPD may benefit from decompression by fenestration of the femoral head. Experience in adult-onset osteonecrosis and our early experience suggest that some patients may benefit from these adjunctive treatments. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Juvenile Myelomonocytic Leukemia (JMML) (For Parents)

    MedlinePlus

    ... TV, Video Games, and the Internet Juvenile Myelomonocytic Leukemia (JMML) KidsHealth > For Parents > Juvenile Myelomonocytic Leukemia (JMML) ... Treatment Coping en español Leucemia mielomonocítica juvenil About Leukemia Leukemia is a type of cancer that affects ...

  3. School-Related Characteristics of Male Juveniles.

    ERIC Educational Resources Information Center

    Sapp, Gary L.; Abbott, Gypsy A.

    School-related characteristics of 256 male juveniles under the jurisdiction of a Family Court system were examined by perusing court records and conducting individual interviews with the juveniles. Results indicated that most juveniles last attended eighth grade, more than 81% had failed at least once, and more than half had fought frequently at…

  4. Do Juveniles Bully More than Young Offenders?

    ERIC Educational Resources Information Center

    Ireland, Jane L.

    2002-01-01

    Study compares bullying behavior among juvenile and young offenders. Ninety-five male juvenile and 196 male young offenders completed two questionnaires, measuring bullying directly and behaviors indicative of "being bullied" or of "bullying others". Juveniles perceived a higher extent of bullying and reported significantly…

  5. Intensive Reading Instruction in Juvenile Correctional Settings

    ERIC Educational Resources Information Center

    Williams, Jacob L.; Wexler, Jade; Roberts, Greg; Carpenter, Clint

    2011-01-01

    Despite 60 years of evidence linking juvenile illiteracy and delinquency, practitioners and policymakers have been painfully slow in the implementation of evidence-based reading interventions for incarcerated juveniles. We will present the Texas Juvenile Justice Tiered Instructional Model, an evidence-based reading program model created…

  6. The Juvenile Court: Changes and Challenges.

    ERIC Educational Resources Information Center

    Feld, Barry C.

    2000-01-01

    Explores the changes in the juvenile court system, in particular, the juvenile waiver and sentencing laws, as it transformed from a social welfare agency into a type of criminal court system for young offenders. Addresses whether states should create an integrated juvenile and criminal justice system. (CMK)

  7. On the Prevention of Juvenile Crime

    ERIC Educational Resources Information Center

    Lelekov, V. A.; Kosheleva, E. V.

    2008-01-01

    Crimes committed by juveniles are among the most urgent social problems. Juvenile crime is as prevalent as crime itself is, and it has not been solved completely in any society and cannot be solved through law enforcement measures alone. In this article, the authors discuss the dynamics and structure of juvenile crime in Russia and present data…

  8. Guidelines for Juvenile Information Sharing. OJJDP Report

    ERIC Educational Resources Information Center

    Mankey, Jennifer; Baca, Patricia; Rondenell, Stephanie; Webb, Marilyn; McHugh, Denise

    2006-01-01

    The juvenile information sharing (JIS) guidelines were prepared by the Center for Network Development (CND) for the Office of Juvenile Justice and Delinquency Prevention (OJJDP). The guidelines suggest a course of action for key agency and organization stakeholders involved in a state or local effort to implement and sustain juvenile information…

  9. On the Prevention of Juvenile Crime

    ERIC Educational Resources Information Center

    Lelekov, V. A.; Kosheleva, E. V.

    2008-01-01

    Crimes committed by juveniles are among the most urgent social problems. Juvenile crime is as prevalent as crime itself is, and it has not been solved completely in any society and cannot be solved through law enforcement measures alone. In this article, the authors discuss the dynamics and structure of juvenile crime in Russia and present data…

  10. Sex Differences in Attributions of Juvenile Delinquency.

    ERIC Educational Resources Information Center

    Sagatun, Inger J.

    This paper is an application of attribution theory to the processing of juvenile delinquents in an attempt to understand the differential treatment of female and male offenders within the juvenile justice system. The paper explores the attributions of juvenile delinquency both by male and female minors, by male and female parents, and by male and…

  11. Intensive Reading Instruction in Juvenile Correctional Settings

    ERIC Educational Resources Information Center

    Williams, Jacob L.; Wexler, Jade; Roberts, Greg; Carpenter, Clint

    2011-01-01

    Despite 60 years of evidence linking juvenile illiteracy and delinquency, practitioners and policymakers have been painfully slow in the implementation of evidence-based reading interventions for incarcerated juveniles. We will present the Texas Juvenile Justice Tiered Instructional Model, an evidence-based reading program model created…

  12. Disability and Juvenile Delinquency: Issues and Trends

    ERIC Educational Resources Information Center

    Morris, Kimberly A.; Morris, Richard J.

    2006-01-01

    The US juvenile justice system has gone through many changes since its inception in the late 1890s. Even with these changes and more than 100 years of empirical research, there is a paucity of literature published on juvenile delinquents with disabilities. The present article focuses on juvenile delinquents with disabilities, addressing…

  13. Reforming Our Expectations about Juvenile Justice

    ERIC Educational Resources Information Center

    Rodriguez, Pamela F.; Baille, Daphne M.

    2010-01-01

    Typing the term "juvenile justice reform" into a Google[TM] search will result in 60 pages of entries. But what is meant by juvenile justice reform? What does it look like? How will one know when it is achieved? This article defines juvenile justice reform, discusses the principles of effective reform, and describes the practice of…

  14. Prevention of Serious and Violent Juvenile Offending. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Wasserman, Gail A.; Miller, Laurie S.; Cothern, Lynn

    This bulletin explores the proximal risk factors for juvenile offending, reviews the early developmental precursors to violent offending, and summarizes approaches to prevention. It also discusses components of intervention programs, limitations of single-focus prevention, examples of multi systemic interventions, and limitations of prevention…

  15. Race as a Factor in Juvenile Arrests. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Pope, Carl E.; Snyder, Howard E.

    This bulletin examines the effect of race on police decisions to take juvenile offenders into custody. Analysis of 1997 and 1998 data on 17 states from the Federal Bureau of Investigation's National Incident-Based Reporting System indicates that there is no evidence to support the hypothesis that police are more likely to arrest nonwhite juvenile…

  16. Mobilizing Communities To Prevent Juvenile Crime. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Bownes, Donna; Ingersoll, Sarah

    Through Title V Incentive Grants for Local Delinquency Prevention Programs (Community Prevention Grants), the Office of Juvenile Justice and Delinquency Prevention (OJJDP) allocated $20 million in fiscal year 1997 to states to complement law enforcement and justice system efforts by helping local communities foster strong families and nurture…

  17. Special Education and the Juvenile Justice System. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Burrell, Sue; Warboys, Loren

    This bulletin summarizes provisions of federal law as they pertain to special education and juvenile justice. It discusses provisions of the Individuals with Disabilities Education Act 1997 including: the definition of disability; free appropriate public education; identification, referral, and evaluation; the individualized education program…

  18. Addictive neurons

    PubMed Central

    Kodirov, Sodikdjon A.

    2017-01-01

    Since the reward center is considered to be the area tegmentalis ventralis of the hypothalamus, logically its neurons could mainly be responsible for addiction. However, the literature asserts that almost any neurons of CNS can respond to one or another addictive compound. Obviously not only addictive nicotine, but also alcohol, amphetamine, cannabis, cocaine, heroin and morphine may influence dopaminergic cells alone in VTA. Moreover, paradoxically some of these drugs ameliorate symptoms, counterbalance syndromes, cure diseases and improve health, not only those related to the CNS and in adults, but also almost all other organs and in children, e.g. epilepsy. PMID:28649663

  19. Transfer of Juvenile Cases to Criminal Court.

    PubMed

    Lee, Soo Jung; Kraus, Louis J

    2016-01-01

    The first juvenile court was founded in 1899 with the focus on rehabilitation of a juvenile offender as opposed to punishment in adult court. Determining culpability and disposition for adolescents has become a source of much discussion. With serious crimes, juvenile delinquents may be transferred from juvenile court to adult criminal court; this practice became more prevalent in the past century. However, growing knowledge of adolescent development has mitigated the culpability of youth offenders and resulted in judicial decisions influential to juvenile dispositions. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Factors affecting attitudes toward juvenile sex offenders.

    PubMed

    Sahlstrom, Kimberly J; Jeglic, Elizabeth L

    2008-01-01

    This study investigated attitudes toward juvenile sex offenders and factors influencing those attitudes. Additionally, the influences of perpetrator characteristics such as age, gender, and ethnicity on societal attitudes towards intervention requirements were also investigated. Overall, attitudes toward juvenile sex offenders and their treatment amenability were negative. No differences in attitudes toward juvenile sex offenders were found between those who had been victims of sexual abuse and those that had not. Sex offenses committed by juvenile female sex offenders were viewed to be more serious and require more intervention than those committed by juvenile male sex offenders.

  1. Juvenile Justice and Substance Use

    ERIC Educational Resources Information Center

    Chassin, Laurie

    2008-01-01

    Laurie Chassin focuses on the elevated prevalence of substance use disorders among young offenders in the juvenile justice system and on efforts by the justice system to provide treatment for these disorders. She emphasizes the importance of diagnosing and treating these disorders, which are linked both with continued offending and with a broad…

  2. Juvenile Diabetes and Rehabilitation Counseling.

    ERIC Educational Resources Information Center

    Stone, J. Blair; Gregg, Charles H.

    1981-01-01

    Severe complications of diabetes are more likely to occur with the juvenile diabetic and problems of psychosocial adjustment are recurring and difficult. Implications for the rehabilitation counselor are discussed in terms of employment considerations, the effects of complications, genetic counseling, and cooperation with other professionals.…

  3. Juvenile Diabetes and Rehabilitation Counseling.

    ERIC Educational Resources Information Center

    Stone, J. Blair; Gregg, Charles H.

    1981-01-01

    Severe complications of diabetes are more likely to occur with the juvenile diabetic and problems of psychosocial adjustment are recurring and difficult. Implications for the rehabilitation counselor are discussed in terms of employment considerations, the effects of complications, genetic counseling, and cooperation with other professionals.…

  4. Types of Juvenile Sex Offenders

    ERIC Educational Resources Information Center

    Bauman, Sheri

    2002-01-01

    Although juvenile sex offenders (JSOs) account for a significant percentage of sex crimes committed in this country, researchers have only recently begun to study this population. One line of inquiry has been to investigate sub-types of offenders, in order to determine whether different types of offenders have different personality profiles and…

  5. Juvenile Criminals: Who Are They?

    ERIC Educational Resources Information Center

    Antonov, A. I.; Lebed, O. L.

    2005-01-01

    Many adolescents who were born in the late 1970s and 1980s in Russia became juvenile criminals due to the change in the social structure, the proclamation of the values of the comfortable way of life, the institution of property ownership and so forth. Many young people have to help relatives who are in need, and this as well often causes them to…

  6. Treatment of juvenile recurrent parotitis.

    PubMed

    Katz, Philippe; Hartl, Dana M; Guerre, Agnès

    2009-12-01

    Juvenile recurrent parotitis (JRP) can be a debilitating illness in children. Knowing how to recognize and diagnose it for early treatment avoids recurrences that could lead to significant destruction of the glandular parenchyma. This article discusses the various therapeutic modalities proposed in the literature (medical treatment or sialendoscopy) and describes the authors' treatment of choice of combining antibiotics and iodinated oil sialography.

  7. Juvenile Court: Today and Tomorrow.

    ERIC Educational Resources Information Center

    Update on Law-Related Education, 2000

    2000-01-01

    Discusses whether juveniles who commit criminal law violations should be tried in the same courts as adults. Addresses the issue of transfers that is a legal mechanism used to move youth to criminal court. Considers alternative proposals for handling youth brought to the judicial system and the role of the federal government. (CMK)

  8. [Sex-linked juvenile retinoschisis].

    PubMed

    François, P; Turut, P; Soltysik, C; Hache, J C

    1976-02-01

    About 13 observations of sexe linked juvenile retinoschisis, the authors describe the ophthalmoscopic, fluorographic and functional aspects of the disease whose caracteristics are:--its sexe linked recessive heredity; --its clinical characterestics associating: a microcystic macular degeneration, peripheral retinal lesions, vitreous body alterations, --an electroretinogram of the negative type.

  9. Juvenile Court: Today and Tomorrow.

    ERIC Educational Resources Information Center

    Update on Law-Related Education, 2000

    2000-01-01

    Discusses whether juveniles who commit criminal law violations should be tried in the same courts as adults. Addresses the issue of transfers that is a legal mechanism used to move youth to criminal court. Considers alternative proposals for handling youth brought to the judicial system and the role of the federal government. (CMK)

  10. Juvenile Justice: A Bibliographic Essay.

    ERIC Educational Resources Information Center

    Kondak, Ann

    1979-01-01

    Provides information on the background and legal framework of the juvenile justice system, the issues that confront it, and the pressures for change, as well as noting some sources of information on the system. Available from American Association of Law Libraries, 53 West Jackson Blvd., Suite 1201, Chicago, Illinois 60604; sc $4.00. (Author/IRT)

  11. Juvenile Criminals: Who Are They?

    ERIC Educational Resources Information Center

    Antonov, A. I.; Lebed, O. L.

    2005-01-01

    Many adolescents who were born in the late 1970s and 1980s in Russia became juvenile criminals due to the change in the social structure, the proclamation of the values of the comfortable way of life, the institution of property ownership and so forth. Many young people have to help relatives who are in need, and this as well often causes them to…

  12. Paleoamygdala: morphogenesis of the posterior cortical nucleus of the rat amygdaloid complex of the brain during the early juvenile period.

    PubMed

    Akhmadeev, A V; Kalimullina, L B

    2014-09-01

    Sex-related differences and the dynamic of formation of the posterior cortical nucleus of the rat amygdaloid complex were revealed in the early juvenile period by planimetric characteristics, numbers of neurons and glial cells, and glial and apoptotic indexes reflecting morphological restructuring on postnatal days 21, 24, 28, and 31.

  13. Juvenile Crime, Juvenile Justice. Panel on Juvenile Crime: Prevention, Treatment, and Control.

    ERIC Educational Resources Information Center

    McCord, Joan, Ed.; Widom, Cathy Spatz, Ed.; Crowell, Nancy A., Ed.

    This book discusses patterns and trends in crimes committed by children and adolescents, analyzing youth crime as a subset of general crime and studying the impact of race and gender. It evaluates different approaches to forecasting future crime rates. Data come from a national panel that examined what is known about juvenile crime and its…

  14. Juvenile Crime, Juvenile Justice. Panel on Juvenile Crime: Prevention, Treatment, and Control.

    ERIC Educational Resources Information Center

    McCord, Joan, Ed.; Widom, Cathy Spatz, Ed.; Crowell, Nancy A., Ed.

    This book discusses patterns and trends in crimes committed by children and adolescents, analyzing youth crime as a subset of general crime and studying the impact of race and gender. It evaluates different approaches to forecasting future crime rates. Data come from a national panel that examined what is known about juvenile crime and its…

  15. Farnesol-Detecting Olfactory Neurons in Drosophila

    PubMed Central

    Ronderos, David S.; Lin, Chun-Chieh; Potter, Christopher J.

    2014-01-01

    We set out to deorphanize a subset of putative Drosophila odorant receptors expressed in trichoid sensilla using a transgenic in vivo misexpression approach. We identified farnesol as a potent and specific activator for the orphan odorant receptor Or83c. Farnesol is an intermediate in juvenile hormone biosynthesis, but is also produced by ripe citrus fruit peels. Here, we show that farnesol stimulates robust activation of Or83c-expressing olfactory neurons, even at high dilutions. The CD36 homolog Snmp1 is required for normal farnesol response kinetics. The neurons expressing Or83c are found in a subset of poorly characterized intermediate sensilla. We show that these neurons mediate attraction behavior to low concentrations of farnesol and that Or83c receptor mutants are defective for this behavior. Or83c neurons innervate the DC3 glomerulus in the antennal lobe and projection neurons relaying information from this glomerulus to higher brain centers target a region of the lateral horn previously implicated in pheromone perception. Our findings identify a sensitive, narrowly tuned receptor that mediates attraction behavior to farnesol and demonstrates an effective approach to deorphanizing odorant receptors expressed in neurons located in intermediate and trichoid sensilla that may not function in the classical “empty basiconic neuron” system. PMID:24623773

  16. A Practical Approach to Juvenile Dermatomyositis and Juvenile Scleroderma.

    PubMed

    McCann, Liza J; Pain, Clare E

    2016-02-01

    Juvenile dermatomyositis and juvenile scleroderma are rare multisystem autoimmune disorders. Although they share some pathognomonic hallmarks with adult onset myositis or scleroderma, there are significant differences in presentation, characteristics and associated features when the diseases present in childhood. In view of this, and the rarity of the conditions, it is important for care to be led by teams with expertise in pediatric rheumatology conditions. Prognosis has improved significantly in the West; likely due to early diagnosis and aggressive treatment with immunosuppressive medications. However, this trend is not replicated in the developing world. Early recognition of these diseases is crucial to achieve rapid and sustained remission and prevent disease or medication associated complications. This article aims to provide a practical overview for recognition, diagnosis and treatment of these conditions.

  17. Regulation of GABA Equilibrium Potential by mGluRs in Rat Hippocampal CA1 Neurons

    PubMed Central

    Yang, Bo; Rajput, Padmesh S.; Kumar, Ujendra; Sastry, Bhagavatula R.

    2015-01-01

    The equilibrium potential for GABA-A receptor mediated currents (EGABA) in neonatal central neurons is set at a relatively depolarized level, which is suggested to be caused by a low expression of K+/Cl- co-transporter (KCC2) but a relatively high expression of Na+-K+-Cl- cotransporter (NKCC1). Theta-burst stimulation (TBS) in stratum radiatum induces a negative shift in EGABA in juvenile hippocampal CA1 pyramidal neurons. In the current study, the effects of TBS on EGABA in neonatal and juvenile hippocampal CA1 neurons and the underlying mechanisms were examined. Metabotropic glutamate receptors (mGluRs) are suggested to modulate KCC2 and NKCC1 levels in cortical neurons. Therefore, the involvement of mGluRs in the regulation of KCC2 or NKCC1 activity, and thus EGABA, following TBS was also investigated. Whole-cell patch recordings were made from Wistar rat hippocampal CA1 pyramidal neurons, in a slice preparation. In neonates, TBS induces a positive shift in EGABA, which was prevented by NKCC1 antisense but not NKCC1 sense mRNA. (RS)-a-Methyl-4-carboxyphenylglycine (MCPG), a group I and II mGluR antagonist, blocked TBS-induced shifts in both juvenile and neonatal hippocampal neurons. While blockade of mGluR1 or mGluR5 alone could interfere with TBS-induced shifts in EGABA in neonates, only a combined blockade could do the same in juveniles. These results indicate that TBS induces a negative shift in EGABA in juvenile hippocampal neurons but a positive shift in neonatal hippocampal neurons via corresponding changes in KCC2 and NKCC1 expressions, respectively. mGluR activation seems to be necessary for both shifts to occur while the specific receptor subtype involved seems to vary. PMID:26389591

  18. Neurons other than motor neurons in motor neuron disease.

    PubMed

    Ruffoli, Riccardo; Biagioni, Francesca; Busceti, Carla L; Gaglione, Anderson; Ryskalin, Larisa; Gambardella, Stefano; Frati, Alessandro; Fornai, Francesco

    2017-11-01

    Amyotrophic lateral sclerosis (ALS) is typically defined by a loss of motor neurons in the central nervous system. Accordingly, morphological analysis for decades considered motor neurons (in the cortex, brainstem and spinal cord) as the neuronal population selectively involved in ALS. Similarly, this was considered the pathological marker to score disease severity ex vivo both in patients and experimental models. However, the concept of non-autonomous motor neuron death was used recently to indicate the need for additional cell types to produce motor neuron death in ALS. This means that motor neuron loss occurs only when they are connected with other cell types. This concept originally emphasized the need for resident glia as well as non-resident inflammatory cells. Nowadays, the additional role of neurons other than motor neurons emerged in the scenario to induce non-autonomous motor neuron death. In fact, in ALS neurons diverse from motor neurons are involved. These cells play multiple roles in ALS: (i) they participate in the chain of events to produce motor neuron loss; (ii) they may even degenerate more than and before motor neurons. In the present manuscript evidence about multi-neuronal involvement in ALS patients and experimental models is discussed. Specific sub-classes of neurons in the whole spinal cord are reported either to degenerate or to trigger neuronal degeneration, thus portraying ALS as a whole spinal cord disorder rather than a disease affecting motor neurons solely. This is associated with a novel concept in motor neuron disease which recruits abnormal mechanisms of cell to cell communication.

  19. 8 CFR 236.3 - Detention and release of juveniles.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Detention and release of juveniles. 236.3... Aliens Prior to Order of Removal § 236.3 Detention and release of juveniles. (a) Juveniles. A juvenile is defined as an alien under the age of 18 years. (b) Release. Juveniles for whom bond has been posted,...

  20. Juvenile amyotrophic lateral sclerosis: Classical wine glass sign on magnetic resonance imaging

    PubMed Central

    Kumar, Saurabh; Aga, Pallavi; Gupta, Aakansha; Kohli, Neera

    2016-01-01

    Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig disease, is a chronic degenerative neurologic disease and is characterized by the selective involvement of the motor system. Usually, patients present with upper motor neuron (UMN) and lower motor neuron compromise. Degeneration of the UMN in the cerebral cortex is one of the main pathologic changes in ALS. These changes usually affect corticospinal tracts leading to degeneration of the fibers which show characteristic hyperintensities along the tracts leading to the “wine glass sign.” Patients with ALS usually present in the sixth decade of life; presentation in pediatric age in the form of juvenile ALS being rare. PMID:27195035

  1. Methylphenidate and the juvenile brain: enhancement of attention at the expense of cortical plasticity?

    PubMed

    Urban, Kimberly R; Gao, Wen-Jun

    2013-12-01

    Methylphenidate (Ritalin) is the most commonly prescribed psychoactive drug for juveniles and adolescents. Used to treat attention-deficit/hyperactivity disorder (ADHD) and for cognitive enhancement in healthy individuals, it has been regarded as a relatively safe medication for the past several decades. However, a thorough review of the literature reveals that the age-dependent activities of the drug, as well as potential developmental effects, are largely ignored. In addition, the diagnosis of ADHD is subjective, leaving open the possibility of misdiagnosis and excessive prescription of the drug. Recent studies have suggested that early life exposure of healthy rodent models to methylphenidate resulted in altered sleep/wake cycle, heightened stress reactivity, and, in fact, a dosage previously thought of as therapeutic depressed neuronal function in juvenile rats. Furthermore, juvenile rats exposed to low-dose methylphenidate displayed alterations in neural markers of plasticity, indicating that the drug might alter the basic properties of prefrontal cortical circuits. In this review of the current literature, we propose that juvenile exposure to methylphenidate may cause abnormal prefrontal function and impaired plasticity in the healthy brain, strengthening the case for developing a more thorough understanding of methylphenidate's actions on the developing, juvenile brain, as well as better diagnostic measures for ADHD. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Methylphenidate and the Juvenile Brain: Enhancement of Attention at the Expense of Cortical Plasticity?

    PubMed Central

    Urban, Kimberly R.; Gao, Wen-Jun

    2013-01-01

    Methylphenidate (Ritalin) is the most commonly prescribed psychoactive drug for juveniles and adolescents. Used to treat attention-deficit/hyperactivity disorder (ADHD) and for cognitive enhancement in healthy individuals, it has been regarded as a relatively safe medication for the past several decades. However, a thorough review of the literature reveals that the age-dependent activities of the drug, as well as potential developmental effects, are largely ignored. In addition, the diagnosis of ADHD is subjective, leaving open the possibility of misdiagnosis and excessive prescription of the drug. Recent studies have suggested that early life exposure of healthy rodent models to methylphenidate resulted in altered sleep/wake cycle, heightened stress reactivity, and, in fact, a dosage previously thought of as therapeutic depressed neuronal function in juvenile rats. Furthermore, juvenile rats exposed to low-dose methylphenidate displayed alterations in neural markers of plasticity, indicating that the drug might alter the basic properties of prefrontal cortical circuits. In this review of the current literature, we propose that juvenile exposure to methylphenidate may cause abnormal prefrontal function and impaired plasticity in the healthy brain, strengthening the case for developing a more thorough understanding of methylphenidate’s actions on the developing, juvenile brain, as well as better diagnostic measures for ADHD. PMID:24095262

  3. Juvenile morphology in baleen whale phylogeny.

    PubMed

    Tsai, Cheng-Hsiu; Fordyce, R Ewan

    2014-09-01

    Phylogenetic reconstructions are sensitive to the influence of ontogeny on morphology. Here, we use foetal/neonatal specimens of known species of living baleen whales (Cetacea: Mysticeti) to show how juvenile morphology of extant species affects phylogenetic placement of the species. In one clade (sei whale, Balaenopteridae), the juvenile is distant from the usual phylogenetic position of adults, but in the other clade (pygmy right whale, Cetotheriidae), the juvenile is close to the adult. Different heterochronic processes at work in the studied species have different influences on juvenile morphology and on phylogenetic placement. This study helps to understand the relationship between evolutionary processes and phylogenetic patterns in baleen whale evolution and, more in general, between phylogeny and ontogeny; likewise, this study provides a proxy how to interpret the phylogeny when fossils that are immature individuals are included. Juvenile individuals in the peramorphic acceleration clades would produce misleading phylogenies, whereas juvenile individuals in the paedomorphic neoteny clades should still provide reliable phylogenetic signals.

  4. Juvenile morphology in baleen whale phylogeny

    NASA Astrophysics Data System (ADS)

    Tsai, Cheng-Hsiu; Fordyce, R. Ewan

    2014-09-01

    Phylogenetic reconstructions are sensitive to the influence of ontogeny on morphology. Here, we use foetal/neonatal specimens of known species of living baleen whales (Cetacea: Mysticeti) to show how juvenile morphology of extant species affects phylogenetic placement of the species. In one clade (sei whale, Balaenopteridae), the juvenile is distant from the usual phylogenetic position of adults, but in the other clade (pygmy right whale, Cetotheriidae), the juvenile is close to the adult. Different heterochronic processes at work in the studied species have different influences on juvenile morphology and on phylogenetic placement. This study helps to understand the relationship between evolutionary processes and phylogenetic patterns in baleen whale evolution and, more in general, between phylogeny and ontogeny; likewise, this study provides a proxy how to interpret the phylogeny when fossils that are immature individuals are included. Juvenile individuals in the peramorphic acceleration clades would produce misleading phylogenies, whereas juvenile individuals in the paedomorphic neoteny clades should still provide reliable phylogenetic signals.

  5. MAPK Signaling Determines Anxiety in the Juvenile Mouse Brain but Depression-Like Behavior in Adults

    PubMed Central

    Wefers, Benedikt; Hitz, Christiane; Hölter, Sabine M.; Trümbach, Dietrich; Hansen, Jens; Weber, Peter; Pütz, Benno; Deussing, Jan M.; de Angelis, Martin Hrabé; Roenneberg, Till; Zheng, Fang; Alzheimer, Christian; Silva, Alcino; Wurst, Wolfgang; Kühn, Ralf

    2012-01-01

    MAP kinase signaling has been implicated in brain development, long-term memory, and the response to antidepressants. Inducible Braf knockout mice, which exhibit protein depletion in principle forebrain neurons, enabled us to unravel a new role of neuronal MAPK signaling for emotional behavior. Braf mice that were induced during adulthood showed normal anxiety but increased depression-like behavior, in accordance with pharmacological findings. In contrast, the inducible or constitutive inactivation of Braf in the juvenile brain leads to normal depression-like behavior but decreased anxiety in adults. In juvenile, constitutive mutants we found no alteration of GABAergic neurotransmission but reduced neuronal arborization in the dentate gyrus. Analysis of gene expression in the hippocampus revealed nine downregulated MAPK target genes that represent candidates to cause the mutant phenotype. Our results reveal the differential function of MAPK signaling in juvenile and adult life phases and emphasize the early postnatal period as critical for the determination of anxiety in adults. Moreover, these results validate inducible gene inactivation as a new valuable approach, allowing it to discriminate between gene function in the adult and the developing postnatal brain. PMID:22529971

  6. JUVENILE DELINQUENCY AND YOUTH CRIME, TASK FORCE REPORT, REPORT ON JUVENILE JUSTICE AND CONSULTANTS PAPERS.

    ERIC Educational Resources Information Center

    President's Commission on Law Enforcement and Administration of Justice, Washington, DC.

    THIS REPORT CONSISTS OF A DETAILED DISCUSSION OF THE JUVENILE COURT SYSTEM AND THE PREVENTION OF DELINQUENCY. THE COMMISSION'S RECOMMENDATIONS ON JUVENILE DELINQUENCY INCLUDE THE AREAS OF THE JUVENILE JUSTICE SYSTEM, HOUSING AND RECREATION, FAMILIES, INVOLVING YOUTHS IN COMMUNITY LIFE, SCHOOLS, AND EMPLOYMENT. THE APPENDIXES, WHICH CONSTITUTE THE…

  7. Planning for Juvenile Detention Reforms: A Structured Approach. Pathways to Juvenile Detention Reform 1.

    ERIC Educational Resources Information Center

    Steinhart, David

    This report is a guide to juvenile detention planning, based largely on the experiences of Juvenile Detention Alternatives Initiative (JDAI) sites. Its eight chapters include: (1) "Why Is Comprehensive Juvenile Detention Planning Needed?"; (2) "Guiding Principles" (e.g., detention planning must be based on adequate data, must…

  8. Black Juveniles in the Juvenile Justice System: A Cause for Alarm.

    ERIC Educational Resources Information Center

    LeFlore, Larry

    This report examines the representation of black youth in the juvenile justice system, describes changes in juvenile justice philosophy, and discusses policy implications. Black youth are overrepresented at all stages of the juvenile justice system compared to white youth. Positivist theories explain this overrepresentation as the result of…

  9. National Implications in Juvenile Justice: The Influence of Juvenile Mentoring Programs on At Risk Youth.

    ERIC Educational Resources Information Center

    Belshaw, Scott H.; Kritsonis, William Allan

    2007-01-01

    In 1972 the federal government created the Juvenile Justice Delinquency Prevention Act that procured funding for various governmental programs to combat the sudden increase in juvenile crime. A provision of this Act set out the creation of mentoring programs to help decrease the juvenile crime rate and dropout rates in secondary schools. This…

  10. Juvenile Justice: A Century of Change. 1999 National Report Series. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Department of Justice, Washington, DC. Office of Juvenile Justice and Delinquency Prevention.

    This report describes the development of the juvenile justice system in the United States. It uses current data to look at where it is heading, and the recent trend of transferring certain juvenile cases to adult criminal court. Section 1 explains that the juvenile justice system was founded on the concept of rehabilitation through individualized…

  11. JUVENILE DELINQUENCY AND YOUTH CRIME, TASK FORCE REPORT, REPORT ON JUVENILE JUSTICE AND CONSULTANTS PAPERS.

    ERIC Educational Resources Information Center

    President's Commission on Law Enforcement and Administration of Justice, Washington, DC.

    THIS REPORT CONSISTS OF A DETAILED DISCUSSION OF THE JUVENILE COURT SYSTEM AND THE PREVENTION OF DELINQUENCY. THE COMMISSION'S RECOMMENDATIONS ON JUVENILE DELINQUENCY INCLUDE THE AREAS OF THE JUVENILE JUSTICE SYSTEM, HOUSING AND RECREATION, FAMILIES, INVOLVING YOUTHS IN COMMUNITY LIFE, SCHOOLS, AND EMPLOYMENT. THE APPENDIXES, WHICH CONSTITUTE THE…

  12. Juvenile Practice Is Not Child's Play: A Handbook for Attorneys Who Represent Juveniles in Texas.

    ERIC Educational Resources Information Center

    2002

    This handbook is an attempt to summarize the most important aspects of juvenile law for a new practitioner, and to offer some additional ideas and strategies to any juvenile defense attorney. The goal is to help improve representation of juveniles across the state of Texas. References to useful books, cases, and statutes are included. The handbook…

  13. Runaway Juvenile Crime? The Context of Juvenile Arrests in America. Research in Brief.

    ERIC Educational Resources Information Center

    Ziedenberg, Jason; Schiraldi, Vincent

    The Violent and Repeat Juvenile Offender Act of 1997 (S-10) was to be debated in the Senate in spring 1998. This bill would blur the distinction between juvenile and adult criminal systems, making it easier to imprison children as young as 14. Supporters of S-10 were citing statistics to indicate that juvenile crime was on the rise. In fact, the…

  14. A Handbook for Juveniles and Parents on Maine's Juvenile Justice System.

    ERIC Educational Resources Information Center

    Mehnert, Irene

    This guide explains Maine's juvenile justice system so that juveniles and/or their parents can know what to expect or what to do in a situation involving juveniles, public officials and the law. Although it is geographically specific, it could serve as a model to other states. The booklet can serve as a checklist to make sure law enforcement…

  15. Black Juveniles in the Juvenile Justice System: A Cause for Alarm.

    ERIC Educational Resources Information Center

    LeFlore, Larry

    This report examines the representation of black youth in the juvenile justice system, describes changes in juvenile justice philosophy, and discusses policy implications. Black youth are overrepresented at all stages of the juvenile justice system compared to white youth. Positivist theories explain this overrepresentation as the result of…

  16. Juvenile offenders: competence to stand trial.

    PubMed

    Soulier, Matthew

    2012-12-01

    This article details the legal background and assists the reader in the preparation and practical conduct of evaluations regarding juvenile adjudicative competency. The material is presented to be useful as a guide to direct questions of competency and covers aspects of evaluation that include: legal standard for competency to stand trial, developmental immaturity, current practice in juvenile competency to stand trial, forensic evaluation of juvenile competency to stand trial, organizing the evaluation, collateral sources of information, psychiatric evaluation of juvenile adjudicative competency, assessment of mental disorder and intellectual disability, assessment of developmental status, assessment of functional abilities for adjudicative competence, and reaching the forensic opinion.

  17. Diagnosing Juvenile Recurrent Parotitis. Case Reports.

    PubMed

    Schorr, Brittany; Mandel, Louis

    2016-01-01

    Diagnosis of juvenile recurrent parotitis is based upon clinical symptomatology, because no positive serologic signs have been identified. Objective confirmation is best obtained from sialographic or ultrasound studies.

  18. Juvenile justice and substance use.

    PubMed

    Chassin, Laurie

    2008-01-01

    Laurie Chassin focuses on the elevated prevalence of substance use disorders among young offenders in the juvenile justice system and on efforts by the justice system to provide treatment for these disorders. She emphasizes the importance of diagnosing and treating these disorders, which are linked both with continued offending and with a broad range of negative effects, such as smoking, risky sexual behavior, violence, and poor educational, occupational, and psychological outcomes. The high rates of substance use problems among young offenders, says Chassin, suggest a large need for treatment. Although young offenders are usually screened for substance use disorders, Chassin notes the need to improve screening methods and to ensure that screening takes place early enough to allow youths to be diverted out of the justice system into community-based programs when appropriate. Cautioning that no single treatment approach has been proven most effective, Chassin describes current standards of "best practices" in treating substance use disorders, examines the extent to which they are implemented in the juvenile justice system, and describes some promising models of care. She highlights several treatment challenges, including the need for better methods of engaging adolescents and their families in treatment and the need to better address environmental risk factors, such as family substance use and deviant peer networks, and co-occurring conditions, such as learning disabilities and other mental health disorders. Chassin advocates policies that encourage wider use of empirically validated therapies and of documented best practices for treating substance use disorders. High relapse rates among youths successfully treated for substance use disorders also point to a greater need for aftercare services and for managing these disorders as chronic illnesses characterized by relapse and remission. A shortage of aftercare services and a lack of service coordination in the

  19. Juvenile Competency to Stand Trial.

    PubMed

    Stepanyan, Sofia T; Sidhu, Shawn S; Bath, Eraka

    2016-01-01

    Competency to stand trial is interpreted as a protected due process right for all defendants and is defined as a defendant's fundamental knowledge and understanding of the criminal charges being filed, roles and procedures within the courtroom, and a general ability to work with the defense counsel. Questions of competency are most often raised by the judge, defense, or the prosecution, and competency evaluations are most often completed by psychiatrists or psychologists with forensic training or work experience. Mental illness, intellectual disability, developmental disorders, and developmental immaturity are the 4 main factors considered in most juvenile competency evaluations.

  20. [Juvenile monomelic amyotrophy: Hirayama disease].

    PubMed

    Drozdowski, W; Baniukiewicz, E; Lewonowska, M

    1998-01-01

    We present three patients with unilateral upper limb weakness (with muscular atrophy)-two of them with distal and one with proximal localization. The disease onset was between 18th end 35-th year of life; the disease course was biphasic (i.e. progressive within first 1 to 3 years, and stabilized during following 4-24 years). The laboratory investigations permitted to diagnose juvenile monomelic amyotrophy, an entity that is very rare outside Japan. Electromyography revealed neurogenic involvement with spinal features also in clinically unaffected muscles. We suggest that these results may support the hypothesis of this disease being a benign variant of spinal muscular atrophy.

  1. Anaesthesia and juvenile Huntington's disease.

    PubMed

    Gupta, K; Leng, C P

    2000-01-01

    Juvenile Huntington's Disease (JHD) is an involuntary movement disorder that comprises both neurological and psychiatric symptoms. Whilst it has many similarities to Huntington's Disease, it is regarded as a separate clinical entity. The anaesthetic plan should be based on careful assessment of the important issues, including the risk of regurgitation and pulmonary aspiration, possible associated autonomic neuropathy, poor respiratory function and the avoidance of precipitating convulsions and clonic spasms. We describe the management of a 12-year-old girl with JHD scheduled for gastroscopy under general anaesthesia necessitating the use of suxamethonium. We suggest an alternative mechanism for the delayed recovery seen in our patient and in other adult case reports.

  2. Predictors of support for juvenile sex offender registration: educated individuals recognize the flaws of juvenile registration.

    PubMed

    Stevenson, Margaret C; Smith, Amy C; Sekely, Ady; Farnum, Katlyn S

    2013-01-01

    We investigated demographic predictors of support for juvenile sex offender registration policies, including education level, gender, political orientation, and age. Participants were 168 individuals recruited from public places in a Midwest community (45% women; M age = 42). In line with hypotheses, as education level increased, support for juvenile registration decreased, as did the belief that juvenile registration protects the community. In addition, as education level increased, belief that the juvenile understood his actions decreased, as did support for juvenile registration when it is framed as ineffective at reducing sex crime. These beliefs mediated the relationship between education level and diminished support for juvenile registration. Implications of these results for the advancement of effective juvenile sex offender policy are discussed.

  3. Lysosomal membrane permeability stimulates protein aggregate formation in neurons of a lysosomal disease.

    PubMed

    Micsenyi, Matthew C; Sikora, Jakub; Stephney, Gloria; Dobrenis, Kostantin; Walkley, Steven U

    2013-06-26

    Protein aggregates are a common pathological feature of neurodegenerative diseases and several lysosomal diseases, but it is currently unclear what aggregates represent for pathogenesis. Here we report the accumulation of intraneuronal aggregates containing the macroautophagy adapter proteins p62 and NBR1 in the neurodegenerative lysosomal disease late-infantile neuronal ceroid lipofuscinosis (CLN2 disease). CLN2 disease is caused by a deficiency in the lysosomal enzyme tripeptidyl peptidase I, which results in aberrant lysosomal storage of catabolites, including the subunit c of mitochondrial ATP synthase (SCMAS). In an effort to define the role of aggregates in CLN2, we evaluated p62 and NBR1 accumulation in the CNS of Cln2(-/-) mice. Although increases in p62 and NBR1 often suggest compromised degradative mechanisms, we found normal ubiquitin-proteasome system function and only modest inefficiency in macroautophagy late in disease. Importantly, we identified that SCMAS colocalizes with p62 in extra-lysosomal aggregates in Cln2(-/-) neurons in vivo. This finding is consistent with SCMAS being released from lysosomes, an event known as lysosomal membrane permeability (LMP). We predicted that LMP and storage release from lysosomes results in the sequestration of this material as cytosolic aggregates by p62 and NBR1. Notably, LMP induction in primary neuronal cultures generates p62-positive aggregates and promotes p62 localization to lysosomal membranes, supporting our in vivo findings. We conclude that LMP is a previously unrecognized pathogenic event in CLN2 disease that stimulates cytosolic aggregate formation. Furthermore, we offer a novel role for p62 in response to LMP that may be relevant for other diseases exhibiting p62 accumulation.

  4. Families, Juvenile Justice and Children's Mental Health.

    ERIC Educational Resources Information Center

    McManus, Marilyn C., Ed.

    1997-01-01

    The theme issue of this bulletin is a discussion of youth with emotional disturbances who are in the juvenile justice system and how to meet their needs. Articles include: (1) "Responding to the Mental Health Needs of Youth in the Juvenile Justice System" (Susan Rotenberg); (2) "Prevalence of Mental Disorders among Youth in the…

  5. Students with Juvenile Arthritis Participating in Recess

    ERIC Educational Resources Information Center

    Lucas, Matthew D.

    2009-01-01

    The participation of a student with juvenile arthritis in recess can often be both challenging and rewarding for the student and general education teacher. This paper will address common characteristics of students with juvenile arthritis and present basic solutions to improve the education of these students in the recess setting. Initially the…

  6. Juvenile Offenders and Victims: 2006 National Report

    ERIC Educational Resources Information Center

    Snyder, Howard N.; Sickmund, Melissa

    2006-01-01

    This report presents comprehensive information on juvenile crime, violence, and victimization and on the juvenile justice system. This report brings together the latest available statistics from a variety of sources and includes numerous tables, graphs, and maps, accompanied by analyses in clear, nontechnical language. The report offers Congress,…

  7. Intelligence Score Profiles of Female Juvenile Offenders

    ERIC Educational Resources Information Center

    Werner, Shelby Spare; Hart, Kathleen J.; Ficke, Susan L.

    2016-01-01

    Previous studies have found that male juvenile offenders typically obtain low scores on measures of intelligence, often with a pattern of higher scores on measures of nonverbal relative to verbal tasks. The research on the intelligence performance of female juvenile offenders is limited. This study explored the Wechsler Intelligence Scale for…

  8. Thermomechanical pulping of loblolly pine juvenile wood

    Treesearch

    Gary C. Myers

    2002-01-01

    Intensive forest management, with a heavy emphasis on ecosystem management and restoring or maintaining forest health, will result in the removal of smaller diameter materials from the forest. This increases the probability of higher juvenile wood content in the harvested materials. The purpose of this study was to compare the performance of loblolly pine juvenile and...

  9. Changes in Juvenile Justice in China.

    ERIC Educational Resources Information Center

    Wong, Dennis S. W.

    2001-01-01

    Discusses rising juvenile and youth crime in China, highlighting the essence of Chinese Marxist criminological thought and changing conceptions of delinquency from the postrevolutionary period to the present; examining official responses to delinquency and the recent development of juvenile justice; and suggesting that current delinquency control…

  10. Intelligence Score Profiles of Female Juvenile Offenders

    ERIC Educational Resources Information Center

    Werner, Shelby Spare; Hart, Kathleen J.; Ficke, Susan L.

    2016-01-01

    Previous studies have found that male juvenile offenders typically obtain low scores on measures of intelligence, often with a pattern of higher scores on measures of nonverbal relative to verbal tasks. The research on the intelligence performance of female juvenile offenders is limited. This study explored the Wechsler Intelligence Scale for…

  11. Juvenile Obesity, Physical Activity, and Lifestyle Changes.

    ERIC Educational Resources Information Center

    Bar-Or, Oded

    2000-01-01

    Because many obese children become obese adults, the recent rapid increase in juvenile obesity poses a major public health challenge. Enhanced physical activity is a cornerstone in a multidisciplinary approach to preventing and treating juvenile obesity. Giving exercise recommendations focused for obese youth is critical. Cutting down on sedentary…

  12. Wilderness/Adventure Programs for Juvenile Offenders.

    ERIC Educational Resources Information Center

    Kimball, Richard Owen

    Over 80 wilderness/adventure programs have emerged as a valuable alternative to traditional treatment for juvenile offenders, especially in combination with other services. Participants are referred from many points in the juvenile justice system by agents who should have a thorough understanding of wilderness programs so as to prepare the…

  13. Juvenile Offender Comprehensive Reentry Substance Abuse Treatment

    ERIC Educational Resources Information Center

    Watson, Donnie W.

    2004-01-01

    The literature provides ample evidence of the relationship of substance abuse to crime. Research over the last 20 years has established a strong correlation between substance abuse and juvenile delinquency (held, 1998). Currently, there are more than 350,000 juveniles on probation and in continuing care programs in the U.S. who have substance…

  14. Assessing Reoffense Risk with Juvenile Sexual Offenders.

    ERIC Educational Resources Information Center

    Kahn, Timothy J.; Chambers, Heather J.

    1991-01-01

    Summarizes a two-year study of juvenile sexual offenders in Washington. Evaluates both community- and institution-based treatment programs. Offers a demographic profile of the typical juvenile sexual offender and the recidivism data from a mean 20-month follow-up period. Surprisingly few variables were found to have a significant relationship to…

  15. Factors Affecting Attitudes toward Juvenile Sex Offenders

    ERIC Educational Resources Information Center

    Sahlstrom, Kimberly J.; Jeglic, Elizabeth L.

    2008-01-01

    This study investigated attitudes toward juvenile sex offenders and factors influencing those attitudes. Additionally, the influences of perpetrator characteristics such as age, gender, and ethnicity on societal attitudes towards intervention requirements were also investigated. Overall, attitudes toward juvenile sex offenders and their treatment…

  16. Moral Development of Solo Juvenile Sex Offenders

    ERIC Educational Resources Information Center

    Van Vugt, Eveline; Stams, Geert Jan; Dekovic, Maja; Brugman, Daan; Rutten, Esther; Hendriks, Jan

    2008-01-01

    This study compared the moral development of solo juvenile male sex offenders (n = 20) and juvenile male non-offenders (n = 76), aged 13-19 years, from lower socioeconomic and educational backgrounds. The Moral Orientation Measure (MOM) was used to assess punishment- and victim-based moral orientation in sexual and non-sexual situations. Moral…

  17. Juvenile Offenders and Victims: 1999 National Report.

    ERIC Educational Resources Information Center

    Snyder, Howard N.; Sickmund, Melissa

    This report offers the Congress, state legislators, and other state and local policymakers, professors and teachers, juvenile justice professionals, and concerned citizens solid answers to the most frequently asked questions about the nature of juvenile crime and victimization and about the justice system's response. Citing FBI and other data…

  18. Genetic and clinical evaluation of juvenile retinoschisis

    PubMed Central

    Kim, Judy E.; Ruttum, Mark S.; Koeberl, Matthew J.; Hassemer, Eryn L.; Sidjanin, D. J.

    2014-01-01

    Juvenile retinoschisis is a rare retinal dystrophy caused by RS1 gene mutations.1 Clinical examinations and molecular testing definitively diagnosed juvenile retinoschisis in 2 male infants, one of whom had a novel mutation not previously reported in the United States. Genetic testing may be the simplest way to confirm this diagnosis in infants. PMID:19393523

  19. Genetic and clinical evaluation of juvenile retinoschisis.

    PubMed

    Kim, Judy E; Ruttum, Mark S; Koeberl, Matthew J; Hassemer, Eryn L; Sidjanin, D J

    2009-04-01

    Juvenile retinoschisis is a rare retinal dystrophy caused by RS1 gene mutations.(1) Clinical examinations and molecular testing definitively diagnosed juvenile retinoschisis in 2 male infants, one of whom had a novel mutation not previously reported in the United States. Genetic testing may be the simplest way to confirm this diagnosis in infants.

  20. Factors Affecting Attitudes toward Juvenile Sex Offenders

    ERIC Educational Resources Information Center

    Sahlstrom, Kimberly J.; Jeglic, Elizabeth L.

    2008-01-01

    This study investigated attitudes toward juvenile sex offenders and factors influencing those attitudes. Additionally, the influences of perpetrator characteristics such as age, gender, and ethnicity on societal attitudes towards intervention requirements were also investigated. Overall, attitudes toward juvenile sex offenders and their treatment…

  1. Juvenile Obesity, Physical Activity, and Lifestyle Changes.

    ERIC Educational Resources Information Center

    Bar-Or, Oded

    2000-01-01

    Because many obese children become obese adults, the recent rapid increase in juvenile obesity poses a major public health challenge. Enhanced physical activity is a cornerstone in a multidisciplinary approach to preventing and treating juvenile obesity. Giving exercise recommendations focused for obese youth is critical. Cutting down on sedentary…

  2. Moral Development of Solo Juvenile Sex Offenders

    ERIC Educational Resources Information Center

    Van Vugt, Eveline; Stams, Geert Jan; Dekovic, Maja; Brugman, Daan; Rutten, Esther; Hendriks, Jan

    2008-01-01

    This study compared the moral development of solo juvenile male sex offenders (n = 20) and juvenile male non-offenders (n = 76), aged 13-19 years, from lower socioeconomic and educational backgrounds. The Moral Orientation Measure (MOM) was used to assess punishment- and victim-based moral orientation in sexual and non-sexual situations. Moral…

  3. Psychiatric Disorder in a Juvenile Assessment Center

    ERIC Educational Resources Information Center

    McReynolds, Larkin S.; Wasserman, Gail A.; DeComo, Robert E.; John, Reni; Keating, Joseph M.; Nolen, Scott

    2008-01-01

    Juvenile assessment centers (JACs) were developed to address service fragmentation and promote the sharing of information among agencies providing services to youth involved with the juvenile justice system. To date, there are no reports that describe the diagnostic profiles of the youth served by such centers. The authors hypothesize that the…

  4. Juvenile Delinquency: Research, Theory, and Comment.

    ERIC Educational Resources Information Center

    Moore, Bernice Milburn

    While this booklet on juvenile delinquency does not attempt a full review of the literature, it has been designed to further an understanding and appreciation of the social-psychological problems of deviant behavior. The booklet briefly covers the publicity which juvenile delinquency has been given in recent years, as well as the difficulties…

  5. Juveniles' Motivations for Remaining in Prostitution

    ERIC Educational Resources Information Center

    Hwang, Shu-Ling; Bedford, Olwen

    2004-01-01

    Qualitative data from in-depth interviews were collected in 1990-1991, 1992, and 2000 with 49 prostituted juveniles remanded to two rehabilitation centers in Taiwan. These data are analyzed to explore Taiwanese prostituted juveniles' feelings about themselves and their work, their motivations for remaining in prostitution, and their difficulties…

  6. Juvenile Anorexia Nervosa: Family Therapy's Natural Niche

    ERIC Educational Resources Information Center

    Fishman, H. Charles

    2006-01-01

    Juvenile Anorexia Nervosa (AN) is a severe problem both in terms of presenting symptomatology and its tendency toward chronicity. Researchers have consistently shown that family-based approaches are superior to individual approaches for the treatment of juvenile AN. This article addresses the capacity deficit of trained family therapists to treat…

  7. Micropropagation of juvenile and mature american beech

    Treesearch

    Melanie J. Barker; Paula M. Pijut; Michael E. Ostry; David R. Houston

    1997-01-01

    The purpose of this study was to micropropagate juvenile and mature American beech (Fagus grandifolia Ehrh.) resistant to beech bark disease. Shoot tips (from juvenile seedlings and root sprouts of mature trees) and buds from branches of mature trees, were cultured and multiplied on aspen culture medium supplemented with 0.89 ?M 6-benzyladenine, 0.27 ?M a-...

  8. Psychiatric Disorder in a Juvenile Assessment Center

    ERIC Educational Resources Information Center

    McReynolds, Larkin S.; Wasserman, Gail A.; DeComo, Robert E.; John, Reni; Keating, Joseph M.; Nolen, Scott

    2008-01-01

    Juvenile assessment centers (JACs) were developed to address service fragmentation and promote the sharing of information among agencies providing services to youth involved with the juvenile justice system. To date, there are no reports that describe the diagnostic profiles of the youth served by such centers. The authors hypothesize that the…

  9. Juvenile Justice in Indiana: Facing the Issues.

    ERIC Educational Resources Information Center

    Smith, Doreen L.

    The Indiana juvenile justice system is charged with intervening on behalf of youthful offenders for the purposes of providing care, treatment, protection, or rehabilitation. This report provides an overview of the state's juvenile justice system, which has fallen under widespread criticism for many years. The following issues are identified: data…

  10. Juvenile Anorexia Nervosa: Family Therapy's Natural Niche

    ERIC Educational Resources Information Center

    Fishman, H. Charles

    2006-01-01

    Juvenile Anorexia Nervosa (AN) is a severe problem both in terms of presenting symptomatology and its tendency toward chronicity. Researchers have consistently shown that family-based approaches are superior to individual approaches for the treatment of juvenile AN. This article addresses the capacity deficit of trained family therapists to treat…

  11. Systemic juvenile xanthogranuloma with fatal outcome.

    PubMed

    Azorín, Daniel; Torrelo, Antonio; Lassaletta, Alvaro; de Prada, Inmaculada; Colmenero, Isabel; Contra, Trinidad; González-Mediero, Imelda

    2009-01-01

    Juvenile xanthogranuloma is a benign and self-limited disease which usually appears in the skin of children. Visceral involvement has been rarely reported, as has fatal outcome in some affected individuals. We report a case of systemic juvenile xanthogranuloma in a female newborn with mainly skin, bone marrow, and liver involvement, leading to death at the age of 2 months.

  12. Juvenile dispersal in Calomys venustus (Muridae: Sigmodontinae)

    NASA Astrophysics Data System (ADS)

    Priotto, José; Steinmann, Andrea; Provensal, Cecilia; Polop, Jaime

    2004-05-01

    Both spacing behaviour and dispersal movement are viewed as hierarchical processes in which the effects may be expressed at spatial scale. This research was carried out to examine the hypothesis that the presence of parents promotes the dispersal of juveniles from their natal nest and their father or mother home-range, in Calomys venustus.The study was carried out in four 0.25 ha fences (two controls and two experimentals), in a natural pasture. This study had two periods: Father Removal (FR) (August and December 1997; year one) and Mother Removal (MR) (August 1998 and January 1999; year two). For the FR treatment fathers were removed after juveniles were born, but in the MR treatment mothers were removed after the juveniles were weaned. The effect of parents on the dispersal distance of juveniles was analysed with respect to their natal nest and their mother and father home-range. Dispersal distance from the nest of C. venustus was independent of either male or female parent. Juveniles were more dispersing in relation to the centre of activity of their mothers than to that of their fathers, and females were more dispersing than males. Female juveniles overlap their home-range with their parents less than male juveniles do. The differences observed between female and male juveniles would be related to their different sexual maturation times, as well as to the female territoriality.

  13. Utilizing Adventure Education to Rehabilitate Juvenile Delinquents.

    ERIC Educational Resources Information Center

    Golins, Gerald L.

    The use of adventure based education is a new and relatively unresearched but apparently successful practice in the rehabilitation of juvenile delinquents. Courses offered by schools, state social service systems, juvenile courts, youth service bureaus, and other agencies are generally patterned after the standard Outward Bound course and involve…

  14. Juvenile hormone regulation of Drosophila aging

    PubMed Central

    2013-01-01

    Background Juvenile hormone (JH) has been demonstrated to control adult lifespan in a number of non-model insects where surgical removal of the corpora allata eliminates the hormone’s source. In contrast, little is known about how juvenile hormone affects adult Drosophila melanogaster. Previous work suggests that insulin signaling may modulate Drosophila aging in part through its impact on juvenile hormone titer, but no data yet address whether reduction of juvenile hormone is sufficient to control Drosophila life span. Here we adapt a genetic approach to knock out the corpora allata in adult Drosophila melanogaster and characterize adult life history phenotypes produced by reduction of juvenile hormone. With this system we test potential explanations for how juvenile hormone modulates aging. Results A tissue specific driver inducing an inhibitor of a protein phosphatase was used to ablate the corpora allata while permitting normal development of adult flies. Corpora allata knockout adults had greatly reduced fecundity, inhibited oogenesis, impaired adult fat body development and extended lifespan. Treating these adults with the juvenile hormone analog methoprene restored all traits toward wildtype. Knockout females remained relatively long-lived even when crossed into a genotype that blocked all egg production. Dietary restriction further extended the lifespan of knockout females. In an analysis of expression profiles of knockout females in fertile and sterile backgrounds, about 100 genes changed in response to loss of juvenile hormone independent of reproductive state. Conclusions Reduced juvenile hormone alone is sufficient to extend the lifespan of Drosophila melanogaster. Reduced juvenile hormone limits reproduction by inhibiting the production of yolked eggs, and this may arise because juvenile hormone is required for the post-eclosion development of the vitellogenin-producing adult fat body. Our data do not support a mechanism for juvenile hormone control

  15. Bilateral Giant Juvenile Fibroadenoma of Breast.

    PubMed

    Makkar, Nikhil; Singh, Sumitoj; Paul, Surinder; Sandhu, Mandeep Singh; Kumar, Ashok

    2017-06-01

    Fibroadenomas are benign lesions of breast commonly found in young age group. These focal tumours contain both mesenchymal and glandular tissue. Giant juvenile fibroma of breast is rare variant of fibroadenoma found usually in less than 20 years of age. They present with rapid enlargement of single or multiple, discrete, painless large nodule of breast. A 14-years-old premenarche girl presented with large bilateral breast lumps for two months. FNAC showed features of juvenile fibroadenoma. Breast conserving surgical excision of lumps was performed and histopathology confirmed the diagnosis of juvenile fibroadenoma. Giant juvenile fibroadenomas are characterised by rapid enlargement of encapsulated mass. The aetiology is unknown, although end-organ hypersensitivity to normal level of estrogen is postulated. We present a case of bilateral giant juvenile fibroadenoma for its rarity.

  16. Selective suppression of excitatory synapses on GABAergic interneurons by norepinephrine in juvenile rat prefrontal cortical microcircuitry.

    PubMed

    Wang, H-X; Waterhouse, B D; Gao, W-J

    2013-08-29

    The noradrenergic system of the brain is thought to facilitate neuronal processes that promote behavioral activation, alertness, and attention. It is known that norepinephrine (NE) can be significantly elevated in the prefrontal cortex under normal conditions such as arousal and attention, and following the administration of psychostimulants and various other drugs prescribed for psychiatric disorders. However, how NE modulates neuronal activity and synapses in the local prefrontal circuitry remains elusive. In this study, we characterized the actions of NE on individual monosynaptic connections among layer V pyramidal neurons (P) and fast-spiking (FS) GABAergic interneurons in the juvenile (postnatal days 20-23) rat prefrontal local circuitry. We found that NE selectively depresses excitatory synaptic transmission in P-FS connections but has no detectable effect on the excitatory synapses in P-P connections and the inhibitory synapses in FS-P connections. NE apparently exerts distinctly different modulatory actions on identified synapses that target GABAergic interneurons but has no effect on those in the pyramidal neurons in this specific developmental period. These results indicate that, depending on the postsynaptic targets, the effects of NE in prefrontal cortex are synapse-specific, at least in the juvenile animals.

  17. Family transitions and juvenile delinquency.

    PubMed

    Schroeder, Ryan D; Osgood, Aurea K; Oghia, Michael J

    2010-01-01

    There is a large body of research that shows children from non-intact homes show higher rates of juvenile delinquency than children from intact homes, partially due to weaker parental control and supervision in non-intact homes. What has not been adequately addressed in the research is the influence of changes in family structure among individual adolescents over time on delinquent offending. Using the first and third waves of the National Youth Study, we assess the effect of family structure changes on changes in delinquent offending between waves through the intermediate process of changes in family time and parental attachment. Although prior research has documented adolescents in broken homes are more delinquent than youth in intact homes, the process of family dissolution is not associated with concurrent increases in offending. In contrast, family formation through marriage or cohabitation is associated with simultaneous increases in offending. Changes in family time and parental attachment account for a portion of the family formation effect on delinquency, and prior parental attachment and juvenile offending significantly condition the effect of family formation on offending.

  18. Juvenile delinquency and adolescent fatherhood.

    PubMed

    Khurana, Atika; Gavazzi, Stephen M

    2011-08-01

    This study examined ecological risk factors associated with teen paternity in a sample of 2,931 male adolescents coming to the attention of juvenile courts across five midwestern counties. In contrast to previous studies documenting significantly higher rates of teen paternity among African American youth, we found that the European American court-involved youth in our sample were as likely to be teen fathers as their African American counterparts. However, an in-depth examination of the social ecologies of these court-involved youth revealed significant racial differences (regardless of the paternity status), with African American males reporting more prior offenses, delinquent peer associations, traumatic pasts, risky sexual behaviors, and educational risks as compared to European American youth, who reported greater involvement in substance use. Furthermore, logistic regression analyses revealed that after controlling for age and racial background, youth who reported greater exposure to trauma and prior offenses had significantly greater odds of having fathered a child. Surprisingly, youth who were teen fathers reported lower rates of behavioral problems as compared to their nonfathering peers. Given the cross-sectional nature of our data, interpretation of this result is limited. Overall, our findings underscore the need for developing a comprehensive understanding of the ecological risk and protective factors present in the lives of teen fathers coming in contact with the juvenile justice system, as an essential first step in designing effective and relevant intervention programs and services for this at-risk population.

  19. Learning and Memory Deficits in Male Adult Mice Treated with a Benzodiazepine Sleep-Inducing Drug during the Juvenile Period

    PubMed Central

    Furukawa, Yusuke; Tanemura, Kentaro; Igarashi, Katsuhide; Ideta-Otsuka, Maky; Aisaki, Ken-Ichi; Kitajima, Satoshi; Kitagawa, Masanobu; Kanno, Jun

    2016-01-01

    Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the mammalian central nervous system, is also known to be important for brain development. Therefore, disturbances of GABA receptor (GABA-R) mediated signaling (GABA-R signal) during brain development may influence normal brain maturation and cause late-onset brain malfunctions. In this study, we examined whether the stimulation of the GABA-R signal during brain development induces late-onset adverse effects on the brain in adult male mice. To stimulate the GABA-R signal, we used either the benzodiazepine sleep-inducing drug triazolam (TZ) or the non-benzodiazepine drug zolpidem (ZP). We detected learning and memory deficits in mice treated with TZ during the juvenile period, as seen in the fear conditioning test. On the other hand, ZP administration during the juvenile period had little effect. In addition, decreased protein expression of GluR1 and GluR4, which are excitatory neurotransmitter receptors, was detected in the hippocampi of mice treated with TZ during the juvenile period. We measured mRNA expression of the immediate early genes (IEGs), which are neuronal activity markers, in the hippocampus shortly after the administration of TZ or ZP to juvenile mice. Decreased IEG expression was detected in mice with juvenile TZ administration, but not in mice with juvenile ZP administration. Our findings demonstrate that TZ administration during the juvenile period can induce irreversible learning and memory deficits in adult mice. It may need to take an extra care for the prescription of benzodiazepine sleep-inducing drugs to juveniles because it might cause learning and memory deficits. PMID:27489535

  20. Morphometric study on the development of magnocellular neurons of the supraoptic nucleus utilising immunohistochemical methods.

    PubMed Central

    Lazcano, M A; Bentura, M L; Toledano, A

    1990-01-01

    Vasopressin (VP)- and oxytocin (OXY)-producing neurons, components of the rat supraoptic nucleus, have been located with immunohistochemical methods, with the purpose of studying their morphofunctional characteristics during different phases of life (embryonic, juvenile, adult and senile). To carry out this study, an IBAS I (Kontron) computerised image analyser has been utilised. The hormone VP is first detected in the neuronal cytoplasm of 21 days old rat embryos and the hormone OXY appears in the neuronal cytoplasm later, in the newborn phase. The neuronal area with a positive reaction for the two neurohormones has been evaluated and it has been found that the quantity of reaction substance is proportional to the age. In the adult period, VP neurons possess a reaction area (198 microns 2) greater than that of OXY neurons (153 microns 2). In the SON, there are two neuronal shapes, fusiform and round; these shapes coexist in both hormonal types of neurons. Until Day 15 of postnatal development, the SON neurons are intermixed in the interior of the nucleus but in this period a neuronal redistribution is initiated. In the adult phase, OXY neurons are situated preferentially in the anterior, posterior and dorsal parts and VP neurons in the ventral and posterior parts, with both neurons being present in the intermediate part of the SON. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Figs. 12-14 Fig. 15 Fig. 16 PMID:2182586

  1. An Analysis of Juvenile Court Laws in Mississippi.

    ERIC Educational Resources Information Center

    Carter, Walter S., III

    Statutory laws, case laws, and model laws have been provided in this report as a basis for comparing Mississippi's juvenile laws with other juvenile laws. Since legislation concerning juvenile courts is vast, complete legislation is only provided for the State of Mississippi and two model juvenile court acts. Discussion, however, is provided which…

  2. Challenging the Myths: 1999 National Report Series. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Snyder, Howard N.; Sickmund, Melissa

    This bulletin, extracted from "Juvenile Offenders and Victims: 1999 National Report," examines juvenile crime statistics, demonstrating that the predictions in the early 1990s of the emergence of juvenile superpredators (juveniles for whom violence is a way of life) is not supported by current data. Research indicates that levels of…

  3. Profile of Incarcerated Juveniles: Comparison of Male and Female Offenders

    ERIC Educational Resources Information Center

    Martin, Don; Martin, Magy; Dell, Rex; Davis, Candice; Guerrieri, Karen

    2008-01-01

    Effective methods of identifying potential juvenile offenders are critical when developing prevention programs within both state and national juvenile justice systems. The characteristics of juvenile offenders in a large juvenile justice system are examined in this study. Participants live in a Midwestern city with a high rate of crime as…

  4. Juvenile Offenders with Mental Health Needs: Reducing Recidivism Using Wraparound

    ERIC Educational Resources Information Center

    Pullmann, Michael D.; Kerbs, Jodi; Koroloff, Nancy; Veach-White, Ernie; Gaylor, Rita; Sieler, Dede

    2006-01-01

    The rate of youth with mental health needs is disproportionately high in juvenile justice. Wraparound planning involves families and providers in coordinating juvenile justice, mental health, and other services and supports. This study compares data from two groups of juvenile offenders with mental health problems: 106 youth in a juvenile justice…

  5. Profile of Incarcerated Juveniles: Comparison of Male and Female Offenders

    ERIC Educational Resources Information Center

    Martin, Don; Martin, Magy; Dell, Rex; Davis, Candice; Guerrieri, Karen

    2008-01-01

    Effective methods of identifying potential juvenile offenders are critical when developing prevention programs within both state and national juvenile justice systems. The characteristics of juvenile offenders in a large juvenile justice system are examined in this study. Participants live in a Midwestern city with a high rate of crime as…

  6. Juvenile Offenders with Mental Health Needs: Reducing Recidivism Using Wraparound

    ERIC Educational Resources Information Center

    Pullmann, Michael D.; Kerbs, Jodi; Koroloff, Nancy; Veach-White, Ernie; Gaylor, Rita; Sieler, Dede

    2006-01-01

    The rate of youth with mental health needs is disproportionately high in juvenile justice. Wraparound planning involves families and providers in coordinating juvenile justice, mental health, and other services and supports. This study compares data from two groups of juvenile offenders with mental health problems: 106 youth in a juvenile justice…

  7. Vegetative propagation of mature and juvenile northern red oak

    Treesearch

    James J. Zaczek; K. C. Steiner; C. W., Jr. Heuser

    1993-01-01

    Rooting trials were established to evaluate rooting success of cuttings from mature and juvenile, grafted and ungrafted northern red oak (NRO). Buds from 4 mature NRO ortets and juvenile seedlings were grafted onto juvenile and mature rootstock. Cuttings were collected from the grafts and from juvenile and mature shoots developed in situ and...

  8. 8 CFR 1236.3 - Detention and release of juveniles.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Detention and release of juveniles. 1236.3... ORDERED REMOVED Detention of Aliens Prior to Order of Removal § 1236.3 Detention and release of juveniles. (a) Juveniles. A juvenile is defined as an alien under the age of 18 years. (b) Release....

  9. Attitudes regarding life sentences for juvenile offenders.

    PubMed

    Greene, Edie; Evelo, Andrew J

    2013-08-01

    Twice in recent years, the U.S. Supreme Court has considered the constitutionality of life sentences without the possibility of parole (LWOP) for juvenile offenders. Given the public nature of this issue, there is scant information on beliefs about imposing LWOP on juveniles. Attitudes on related issues suggest two possibilities. On the one hand, because public opinion regarding juvenile offenders has become somewhat less punitive recently, LWOP may be viewed as excessively harsh punishment. On the other hand, portrayal of some juvenile offenders as superpredators suggests that LWOP may still have public support. We used survey methodology and the unique "ninth justice paradigm" to examine how an offender's age influences beliefs about the appropriateness of LWOP, and the relationship between those beliefs and punishment-related ideologies. Results showed that, except in the case of murder, the majority of respondents disfavored imposing LWOP on juveniles, though a subset approved broad use of LWOP even for young offenders. In fact, after removing from consideration those who oppose LWOP under any circumstances, youthfulness of the offender has little impact on the beliefs about the types of crimes in which LWOP should be imposed (Study 1) or the mean sentence lengths imposed on juvenile offenders (Study 2). Respondents' punishment goals influenced their attitudes, as did beliefs about the likelihood of rehabilitation and reform. Harsh judgments of juveniles who commit serious crimes may result from dispositional attributions of youthful offenders as irredeemable.

  10. Binge ethanol in adulthood exacerbates negative outcomes following juvenile traumatic brain injury.

    PubMed

    Karelina, Kate; Gaier, Kristopher R; Prabhu, Maya; Wenger, Vanessa; Corrigan, Timothy E D; Weil, Zachary M

    2017-02-01

    Traumatic brain injuries (TBI) are a major public health problem with enormous costs in terms of health care dollars, lost productivity, and reduced quality of life. Alcohol is bidirectionally linked to TBI as many TBI patients are intoxicated at the time of their injury and we recently reported that, in accordance with human epidemiological data, animals injured during juvenile development self-administered significantly more alcohol as adults than did sham injured mice. There are also clinical data that drinking after TBI significantly reduces the efficacy of rehabilitation and leads to poorer long-term outcomes. In order to determine whether juvenile traumatic brain injury also increased the vulnerability of the brain to the toxic effects of high dose alcohol, mice were injured at 21days of age and then seven weeks later treated daily with binge-like levels of alcohol 5g/kg (by oral gavage) for ten days. Binge-like alcohol produced a greater degree of neuronal damage and neuroinflammation in mice that sustained a TBI. Further, mice that sustained a juvenile TBI exhibited mild learning and memory impairments in adulthood following binge alcohol and express a significant increase in hippocampal ectopic localization of newborn neurons. Taken together, these data provide strong evidence that a mild brain injury occurring early in life renders the brain highly vulnerable to the consequences of binge-like alcohol consumption.

  11. Developmental change in the contribution of voltage-gated Ca(2+) channels to the pacemaking of deep cerebellar nuclei neurons.

    PubMed

    Alviña, K; Tara, E; Khodakhah, K

    2016-05-13

    The activity of the deep cerebellar nuclei (DCN) neurons conveys the bulk of the output of the cerebellum. To generate these motor signals, DCN neurons integrate synaptic inputs with their own spontaneous activity. We have previously reported that N-type voltage-gated Ca(2+) channels modulate the spontaneous activity of the majority of juvenile DCN neurons in vitro. Specifically, pharmacologically blocking N-type Ca(2+) channels increases their firing rate causing DCN cells to burst. Adult DCN neurons however, behaved differently. To further investigate this change, we have studied here the effect of cadmium on the firing rate of DCN neurons in acute cerebellar slices obtained from adult (>2 months old) or juvenile (12-21 days old) rats and mice. Strikingly, and in contrast to juvenile DCN cells, cadmium did not affect the pacemaking of adult DCN cells. The activity of Purkinje cells (PCs) however was transformed into high-frequency bursting, regardless the age. Further, we questioned whether these findings could be due to an artifact associated with the added difficulty of preparing adult DCN slices. Hence we proceeded to examine the spontaneous activity of DCN neurons in anesthetized juvenile and adult rats and mice in vivo. When cadmium was injected into the DCN in vivo no significant change in firing rate was observed, conversely to most juvenile DCN neurons which showed high-frequency bursts after cadmium injection. In these same animals, PCs pacemaking showed no developmental difference. Thus our results demonstrate a remarkable age-dependent functional modification in the regulation of DCN neurons pacemaking.

  12. Juvenile curfews: are they an effective and constitutional means of combating juvenile violence?

    PubMed

    Fried, C S

    2001-01-01

    Curfew ordinances have become a popular way to attempt to combat juvenile crime and victimization. Although the Supreme Court has yet to hear a curfew case, several constitutional challenges have been brought in lower federal courts. The cases are replete with psychological assumptions for which there is limited empirical evidence. In applying the "strict scrutiny" standard, several courts have also questioned whether juvenile curfews are narrowly tailored to further the State's interest in reducing juvenile crime and victimization. While public opinion and reports from several police jurisdictions support the utility of juvenile curfews, recent empirical studies indicate that curfews are not effective at reducing juvenile offending or victimization. This paper argues that the emerging evidence does not support the use of juvenile curfews and urges policy makers and the courts to examine the efficacy of curfew legislation. Directions for future research that could be helpful to the courts in applying the Bellotti factors to curfew cases are also suggested.

  13. Sociologic perspectives on juvenile violence.

    PubMed

    Currie, E

    2000-10-01

    In sum, there are four sets of social factors that help us understand why juvenile violence appears when, and where, it does, and why some communities and entire societies are persistently wracked by youth violence whereas others are largely spared its worst expressions. When it comes to the first three factors in particular--deprivation, disorganization, and brutalization--the evidence for these links is as strong as anything in social science, and that evidence is supported by a variety of sources and a variety of methods of investigation. Such investigation includes the knowledge we gain through social intervention. Some of the most effective violence prevention programs are successful precisely because they confront and deflect the social forces that otherwise often lead to violence. Consider, for example, the home-visiting programs that work with poor parents in disorganized communities to lower the risks of child abuse; and some of the more "holistic" or "multisystemic" efforts to work with violent juvenile offenders. The best of these programs work by tackling the problems of social isolation and lack of supports in the community, as well as immediate issues of economic survival for vulnerable families and children. More generally, we know that the availability of steady and rewarding work in the future, of the kind that can reliably sustain a family, is one of the most important factors allowing some youths to "desist" from violence as they mature. These conclusions give us much to be encouraged about, and much to be alarmed about. On the one hand, understanding that youth violence often is rooted in a set of adverse social conditions that are identifiable, and potentially modifiable, is a fundamentally optimistic message. It reminds us that the level of juvenile violence we suffer in America today is neither fated nor inevitable. Other societies that are in many respects much like us suffer far less of it; so could we, and we increasingly understand some

  14. Juvenile Huntington disease in Argentina.

    PubMed

    Gatto, Emilia Mabel; Parisi, Virginia; Etcheverry, José Luis; Sanguinetti, Ana; Cordi, Lorena; Binelli, Adrian; Persi, Gabriel; Squitieri, Ferdinando

    2016-01-01

    We analyzed demographic, clinical and genetic characteristics of juvenile Huntington disease (JHD) and it frequency in an Argentinean cohort. Age at onset was defined as the age at which behavioral, cognitive, psychiatric or motor abnormalities suggestive of JHD were first reported. Clinical and genetic data were similar to other international series, however, in this context we identified the highest JHD frequency reported so far (19.72%; 14/71). Age at onset of JHD is challenging and still under discussion. Our findings reinforce the hypothesis that clinical manifestations, other than the typical movement disorder, may anticipate age at onset of even many years. Analyses of JHD cohorts are required to explore it frequency in populations with different backgrounds to avoid an underestimation of this rare phenotype. Moreover, data from selected populations may open new pathways in therapeutic approaches and may explain new potential correlations between HD presentations and environmental or biological factors.

  15. [Environmental factors in juvenile delinquency].

    PubMed

    Barbagallo, A; Bellia, A; Benvenuto, G; Contiguglia, M A; Cosentino, F

    1975-09-12

    Experimental data are cited for the proposition that the complicated aspects of juvenile delinquency can only be understood and explained by adopting a simultaneous psychological and sociological approach. It is also shown that the manifestations of delinquency, though not its actual presence, may be influenced by sex and a depressed city or rural background. Environmental factors serving as stimulating features and hereditary (i.e. predisposing) factors undoubtedly contribute to the formation of the Ego. The former, however, are elaborated by their receipient and are not sufficient to explain a certain type of behaviour. The influence of cultural models should not be underestimated. These, where predominant, tend to render normative what may be considered as deviant.

  16. [Physiotherapy for juvenile idiopathic arthritis].

    PubMed

    Spamer, M; Georgi, M; Häfner, R; Händel, H; König, M; Haas, J-P

    2012-07-01

    Control of disease activity and recovery of function are major issues in the treatment of children and adolescents suffering from juvenile idiopathic arthritis (JIA). Functional therapies including physiotherapy are important components in the multidisciplinary teamwork and each phase of the disease requires different strategies. While in the active phase of the disease pain alleviation is the main focus, the inactive phase requires strategies for improving motility and function. During remission the aim is to regain general fitness by sports activities. These phase adapted strategies must be individually designed and usually require a combination of different measures including physiotherapy, occupational therapy, massage as well as other physical procedures and sport therapy. There are only few controlled studies investigating the effectiveness of physical therapies in JIA and many strategies are derived from long-standing experience. New results from physiology and sport sciences have contributed to the development in recent years. This report summarizes the basics and main strategies of physical therapy in JIA.

  17. Conceptualizing juvenile prostitution as child maltreatment: findings from the National Juvenile Prostitution Study.

    PubMed

    Mitchell, Kimberly J; Finkelhor, David; Wolak, Janis

    2010-02-01

    Two studies were conducted to identify the incidence (Study 1) and characteristics (Study 2) of juvenile prostitution cases known to law enforcement agencies in the United States. Study 1 revealed a national estimate of 1,450 arrests or detentions (95% confidence interval [CI]: 1,287-1,614) in cases involving juvenile prostitution during a 1-year period. In Study 2, exploratory data were collected from a subsample of 138 cases from police records in 2005. The cases are broadly categorized into three main types: (a) third-party exploiters, (b) solo prostitution, and (c) conventional child sexual abuse (CSA) with payment. Cases were classified into three initial categories based on police orientation toward the juvenile: (a) juveniles as victims (53%), (b) juveniles as delinquents (31%), and (c) juvenile as both victims and delinquents (16%). When examining the status of the juveniles by case type, the authors found that all the juveniles in CSA with payment cases were treated as victims, 66% in third-party exploiters cases, and 11% in solo cases. Findings indicate law enforcement responses to juvenile prostitution are influential in determining whether such youth are viewed as victims of commercial sexual exploitation or as delinquents.

  18. Are antipredator behaviours of hatchery Salmo salar juveniles similar to wild juveniles?

    PubMed

    Salvanes, A G V

    2017-01-27

    This study explores how antipredator behaviour of juvenile Atlantic salmon Salmo salar developed during conventional hatchery rearing of eggs from wild brood stock, compared with the behaviour of wild-caught juveniles from the same population. Juveniles aged 1+ years were tested in two unfamiliar environments; in one S. salar were presented with simulated predator attacks and in the other they were given the opportunity to explore an open-field arena. No difference was found in their spontaneous escape responses or ventilation rate (reflex responses) after simulated predator attacks. Hatchery-reared juveniles were more risk-prone in their behaviours than wild-caught individuals. Hatchery juveniles stayed less time in association with shelter. In the open-field arena, hatchery juveniles were more active than wild juveniles. Hatchery juveniles were also immobile for less time and spent a shorter amount of time than wild juveniles in the fringe of the open-field arena. Salmo salar size had no effect on the observed behaviour. Overall, this study provides empirical evidence that one generation of hatchery rearing does not change reflex responses associated with threats, whereas antipredator behaviour, typically associated with prior experience, was less developed in hatchery-reared than in wild individuals.

  19. Age-Dependent Neurogenesis and Neuron Numbers within the Olfactory Bulb and Hippocampus of Homing Pigeons

    PubMed Central

    Meskenaite, Virginia; Krackow, Sven; Lipp, Hans-Peter

    2016-01-01

    Many birds are supreme long-distance navigators that develop their navigational ability in the first months after fledgling but update the memorized environmental information needed for navigation also later in life. We studied the extent of juvenile and adult neurogenesis that could provide such age-related plasticity in brain regions known to mediate different mechanisms of pigeon homing: the olfactory bulb (OB), and the triangular area of the hippocampal formation (HP tr). Newly generated neurons (visualized by doublecortin, DCX) and mature neurons were counted stereologically in 35 pigeon brains ranging from 1 to 168 months of age. At the age of 1 month, both areas showed maximal proportions of DCX positive neurons, which rapidly declined during the first year of life. In the OB, the number of DCX-positive periglomerular neurons declined further over time, but the number of mature periglomerular cells appeared unchanged. In the hippocampus, the proportion of DCX-positive neurons showed a similar decline yet to a lesser extent. Remarkably, in the triangular area of the hippocampus, the oldest birds showed nearly twice the number of neurons as compared to young adult pigeons, suggesting that adult born neurons in these regions expanded the local circuitry even in aged birds. This increase might reflect navigational experience and, possibly, expanded spatial memory. On the other hand, the decrease of juvenile neurons in the aging OB without adding new circuitry might be related to the improved attachment to the loft characterizing adult and old pigeons. PMID:27445724

  20. Oral Juvenile Xanthogranuloma: Report of Two Cases.

    PubMed

    Israel, Mônica Simões; Carlos, Roman; Pires, Fábio Ramôa

    2017-05-15

    Juvenile xanthogranuloma is a rare non-Langerhans cell histiocytosis that usually occurs in the skin of children. Extracutaneous involvement is rare, and few cases affecting the oral cavity have been reported. The purpose of the present study was to report two cases of oral juvenile xanthogranuloma affecting the lower lip of a 14-year-old girl and the soft palate of a second 14-month-old girl, both present as yellowish papules. The lesions were surgically excised, and histological and immunohistochemical analysis showed a proliferation of non-Langerhans cells histiocytes and foamy cells, fulfilling the morphologic features of juvenile xanthogranuloma. The patients have been followed up, respectively, for 36 and 49 months with no signs of recurrence. Based on these results, juvenile xanthogranuloma should be included in the differential diagnosis of oral yellowish soft-tissue swellings in children and adolescents and should be managed through conservative surgical excision.

  1. 76 FR 54978 - Special Immigrant Juvenile Petitions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-06

    ... from social workers, victim advocates, medical professionals, and others who work with the juvenile... marijuana; Security and related grounds (section 212(a)(3)(A) of the Act, 8 U.S.C. 1182(a)(3)(A));...

  2. Group sexual offending by juvenile females.

    PubMed

    Wijkman, Miriam; Weerman, Frank; Bijleveld, Catrien; Hendriks, Jan

    2015-06-01

    This study examined all group sexual offending cases in the Netherlands between 1995 and 2009 (n = 26) in which at least one juvenile female offender (n = 35) had been adjudicated. Information from court files showed that the majority of juvenile female group sexual offenders have (inter)personal problems and (sexual) abuse experiences. The aims of the offender groups in committing the offense could be categorized in three themes: harassing the victim, sexual gratification, and taking revenge. The reasons why juvenile female offenders participated in a group could be categorized into group dynamics versus instrumental reasons. The findings are contrasted with findings on juvenile male group sexual offenders. Implications of the findings for research and treatment are discussed.

  3. Screening Incarcerated Juveniles Using the MAYSI-2.

    PubMed

    Gilbert, Amy L; Grande, Todd L; Hallman, Janelle; Underwood, Lee A

    2015-01-01

    The high prevalence of mental health disorders among incarcerated juveniles is a matter of national and global concern. Juvenile justice personnel need accurate screening measures that identify youth requiring immediate mental health services. The purpose of this study was threefold: (a) to examine the utility of the Massachusetts Youth Screening Instrument, Version 2 (MAYSI-2) in identifying juveniles with mental health concerns in a large sample of juveniles (N = 4,009), (b) to provide data regarding rates of identified mental health needs in incarcerated youth, and (c) to provide descriptive comparisons to other studies using the MAYSI-2. Mean scores of subscales were compared with the MAYSI-2 normative samples and other recent studies. Results indicated that this population has a high occurrence of mental health symptoms and there is high variability in the severity of the symptoms. In addition, a multivariate analysis of variance test found significant differences in mental health problems across ethnic groups.

  4. Juvenile ossifying fibroma of the maxilla.

    PubMed

    Sun, G; Chen, X; Tang, E; Li, Z; Li, J

    2007-01-01

    Juvenile ossifying fibroma is a rare fibro-osseous neoplasm in young children. This lesion is locally aggressive and spreads quickly, and because it has a very high recurrence rate complete excision is essential. Reported here is a case of a massive juvenile ossifying fibroma of the maxilla in an 11-year-old male child. A titanium mesh was used to reconstruct the facial contour after a left total maxillectomy, achieving a satisfactory facial appearance.

  5. Juvenile dermatomyositis: treatment with intravenous gammaglobulin.

    PubMed

    Collet, E; Dalac, S; Maerens, B; Courtois, J M; Izac, M; Lambert, D

    1994-02-01

    High-dose intravenous gammaglobulin (IVGG) has proved to be effective in the treatment of a number of immune disorders. We report two patients with juvenile dermatomyositis (DM) who improved with IVGG therapy. These patients had become refractory to corticosteroids and had developed unacceptable steroid toxicity. We suggest that IVGG can be useful in the treatment of juvenile DM, by reducing steroid requirements, and replacing immunosuppressive drugs.

  6. Galanin synaptic input to gonadotropin-releasing hormone perikarya in juvenile and adult female mice: implications for sexual maturity.

    PubMed

    Rajendren, G; Li, X

    2001-11-26

    Changes in connectivity of the gonadotropin-releasing hormone (GnRH) neuronal system are believed to occur during the transition from juvenile to adulthood in females. Experiments were designed to investigate whether there is any difference in the number of galanin inputs to GnRH cells located in the organum vasculosum of lamina terminalis-rostral preoptic area (OVLT-rPOA) between juvenile (2 weeks old) and adult (10 weeks old) female mice. Triple label immunofluorescence staining of brain sections for galanin, GnRH and the presynaptic vesicle marker synaptophysin coupled with confocal microscopy was employed to identify galanin synapses to GnRH perikarya. The number of galanin synapses to GnRH cells and the proportion of GnRH cells with galanin input were significantly higher in adults than in juvenile mice. In adult mice, the proportions of GnRH cells with 0, 1, 2, 3, 4, 5 or 6 galanin synapses/cell were comparable to each other whereas in the juveniles the vast majority of them received no galanin synaptic input. A greater number of galanin synapses in adult as compared with juvenile female mice suggests a functional role for galanin in the maturation of the GnRH system.

  7. Examination of the influence of leptin and acute metabolic challenge on RFRP-3 neurons of mice in development and adulthood.

    PubMed

    Poling, Matthew C; Shieh, Morris P; Munaganuru, Nagambika; Luo, Elena; Kauffman, Alexander S

    2014-01-01

    The neuropeptide RFamide-related peptide-3 (RFRP-3; mammalian ortholog to gonadotropin-inhibiting hormone) can inhibit luteinizing hormone (LH) release and increases feeding, but the regulation and development of RFRP-3 neurons remains poorly characterized, especially in mice. We first confirmed that peripheral injections of murine RFRP-3 peptide could markedly suppress LH secretion in adult mice, as in other species. Second, given RFRP-3's reported orexigenic properties, we performed double-label in situ hybridization for metabolic genes in Rfrp neurons of mice. While Rfrp neurons did not readily coexpress neuropeptide Y, thyrotropin-releasing hormone, or MC4R, a small subset of Rfrp neurons did express the leptin receptor in both sexes. Surprisingly, we identified no changes in Rfrp expression or neuronal activation in adult mice after acute fasting. However, we determined that Rfrp mRNA levels in the dorsal-medial nucleus were significantly reduced in adult obese (Ob) mice of both sexes. Given the lower Rfrp levels observed in adult Ob mice, we asked whether leptin might also regulate RFRP-3 neuron development. Rfrp gene expression changed markedly over juvenile development, correlating with the timing of the juvenile 'leptin surge' known to govern hypothalamic feeding circuit development. However, the dramatic developmental changes in juvenile Rfrp expression did not appear to be leptin driven, as the pattern and timing of Rfrp neuron development were unaltered in Ob juveniles. Leptin status modulates RFRP-3 expression in adulthood, but is not required for normal development of the RFRP-3 system. Leptin's regulation of adult RFRP-3 neurons likely occurs primarily via indirect signaling, and may be secondary to obesity, as only a small subset of RFRP-3 neurons express the long form of the leptin receptor (LepRb).

  8. In vivo physiological recording from the lateral line of juvenile zebrafish

    PubMed Central

    Olt, Jennifer; Allen, Claire E.

    2016-01-01

    Key points Zebrafish provide a unique opportunity to investigate in vivo sensory transduction in mature hair cells.We have developed a method for studying the biophysical properties of mature hair cells from the lateral line of juvenile zebrafish.The method involves application of the anaesthetic benzocaine and intubation to maintain ventilation and oxygenation through the gills.The same approach could be used for in vivo functional studies in other sensory and non‐sensory systems from juvenile and adult zebrafish. Abstract Hair cells are sensory receptors responsible for transducing auditory and vestibular information into electrical signals, which are then transmitted with remarkable precision to afferent neurons. The zebrafish lateral line is emerging as an excellent in vivo model for genetic and physiological analysis of hair cells and neurons. However, research has been limited to larval stages because zebrafish become protected from the time of independent feeding under European law (from 5.2 days post‐fertilization (dpf) at 28.5°C). In larval zebrafish, the functional properties of most of hair cells, as well as those of other excitable cells, are still immature. We have developed an experimental protocol to record electrophysiological properties from hair cells of the lateral line in juvenile zebrafish. We found that the anaesthetic benzocaine at 50 mg l−1 was an effective and safe anaesthetic to use on juvenile zebrafish. Concentrations up to 300 mg l−1 did not affect the electrical properties or synaptic vesicle release of juvenile hair cells, unlike the commonly used anaesthetic MS‐222, which reduces the size of basolateral membrane K+ currents. Additionally, we implemented a method to maintain gill movement, and as such respiration and blood oxygenation, via the intubation of > 21 dpf zebrafish. The combination of benzocaine and intubation provides an experimental platform to investigate the physiology of mature hair cells from live

  9. Characteristics of Crimes against Juveniles. Crimes against Children Series. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Finkelhor, David; Ormrod, Richard

    This Bulletin reviews data from the Federal Bureau of Investigation's 1997 National Incident-Based Reporting System (NIBRS) data file that pertain to juvenile victims, revealing that while juveniles made up 26% of the population of the 12 states participating in NIBRS in 1997, they accounted for only 12% of the reported crime victims. At the same…

  10. Governor's Task Force on Juvenile Corrections Alternatives. Recommendations for Oregon's Juvenile Justice System. Final Report.

    ERIC Educational Resources Information Center

    Oregon Governor's Office, Salem.

    This document presents the final report and recommendations of a task force created to study the feasibility of further reducing juvenile training school populations in Oregon. The first section contains an executive summary which briefly reviews the history of Oregon's juvenile justice system and lists findings and recommendations of the task…

  11. Tracking Juvenile Recidivists: Three Options for Creating Statewide, Longitudinal Records of Juvenile Offenders.

    ERIC Educational Resources Information Center

    Rooney, Teresa L.

    This document describes three options for a statewide statistical system for tracking recidivism of juvenile delinquents placed outside their homes in treatment programs. The information is intended for use by the state in allocating resources. The options described involve potential use of juvenile court records, placement data, and/or…

  12. Governor's Task Force on Juvenile Corrections Alternatives. Recommendations for Oregon's Juvenile Justice System. Final Report.

    ERIC Educational Resources Information Center

    Oregon Governor's Office, Salem.

    This document presents the final report and recommendations of a task force created to study the feasibility of further reducing juvenile training school populations in Oregon. The first section contains an executive summary which briefly reviews the history of Oregon's juvenile justice system and lists findings and recommendations of the task…

  13. An Empirical Evaluation of Juvenile Awareness Programs in the United States: Can Juveniles Be "Scared Straight"?

    ERIC Educational Resources Information Center

    Klenowski, Paul M.; Bell, Keith J.; Dodson, Kimberly D.

    2010-01-01

    Juvenile awareness programs like Scared Straight became popular crime prevention strategies during the 1970s. Juvenile offenders and at-risk youth who participate in these programs are taken to prisons where inmates use confrontational methods to recount stories about violence, sex, and abuse perpetrated by fellow inmates while living a life…

  14. An Empirical Evaluation of Juvenile Awareness Programs in the United States: Can Juveniles Be "Scared Straight"?

    ERIC Educational Resources Information Center

    Klenowski, Paul M.; Bell, Keith J.; Dodson, Kimberly D.

    2010-01-01

    Juvenile awareness programs like Scared Straight became popular crime prevention strategies during the 1970s. Juvenile offenders and at-risk youth who participate in these programs are taken to prisons where inmates use confrontational methods to recount stories about violence, sex, and abuse perpetrated by fellow inmates while living a life…

  15. Tracking Juvenile Recidivists: Three Options for Creating Statewide, Longitudinal Records of Juvenile Offenders.

    ERIC Educational Resources Information Center

    Rooney, Teresa L.

    This document describes three options for a statewide statistical system for tracking recidivism of juvenile delinquents placed outside their homes in treatment programs. The information is intended for use by the state in allocating resources. The options described involve potential use of juvenile court records, placement data, and/or…

  16. Juvenile Justice and Delinquency Prevention; Report of the Task Force on Juvenile Justice and Delinquency Prevention.

    ERIC Educational Resources Information Center

    National Inst. for Juvenile Justice and Delinquency Prevention (Dept. of Justice/LEAA), Washington, DC.

    This report presents the national standards for juvenile justice and delinquency prevention developed by the Task Force on Juvenile Justice and Delinquency Prevention appointed in April 1975. The standards run the spectrum from guidelines for the police in areas such as preventive patrols, issuance of citations, and interrogation to…

  17. Legal Advocacy and Juvenile Justice: Negotiations with Public Officials over Juvenile Justice Problems.

    ERIC Educational Resources Information Center

    Illinois Univ., Champaign. Community Research Center.

    The Youth Law Center is a public interest law office whose primary activity has been the Juvenile Justice Legal Advocacy Project. The center has developed a specific procedure for investigating and negotiating juveniles justice problems which involves resolution through negotiation without resorting to litigation. Effective advocacy requires…

  18. Assessing the Mental Health Status of Youth in Juvenile Justice Settings. Juvenile Justice Bulletin

    ERIC Educational Resources Information Center

    Wasserman, Gail A.; Ko, Susan J.; McReynolds, Larkin S.

    2004-01-01

    This Bulletin reports the results of a study that used the Voice DISC, a computerized, self-administered version of the Diagnostic Interview Schedule for Children (DISC), to screen for psychiatric disorders in youth newly admitted to juvenile assessment centers. The Voice DISC offers the following advantages for use in the juvenile justice system:…

  19. The paediatric rheumatologist and orphan disease – a story without happy ending

    PubMed Central

    Roszkiewicz, Justyna; Biernacka-Zielińska, Małgorzata

    2016-01-01

    Orphan diseases are not a common challenge in the everyday practice of the rheumatologist. Despite their extremely rare occurrence one of the patients under our care developed one of them – neuronal ceroid lipofuscinosis, the most frequent neurodegenerative disease observed in the paediatric population. We report a case of 2-year-old girl diagnosed with oligoarticular form of juvenile idiopathic arthritis treated in our Department with steroids and methotrexate and staying in the stage of disease remission. During routine checkups at Outpatient Clinic we observed progressive deterioration of girls neurological condition resulting in ataxia, gait disturbances with no rheumatological cause behind and speech impairment. The appearance of the symptoms was accompanied by frequent episodes of epileptic seizures, with little clinical improvement on combined antiepileptic treatment. Magnetic resonance imaging that we performed showed a picture highly suggestive of neuronal ceroid lipofuscinosis – atrophy of the patients cerebrum and cerebellum. Genetic testing conducted resulted in the diagnosis of late infantile neuronal ceroid lipofuscinosis (LINCL). PMID:27504025

  20. Phagocyte function in juvenile periodontitis.

    PubMed Central

    Repo, H; Saxén, L; Jäättelä, M; Ristola, M; Leirisalo-Repo, M

    1990-01-01

    We studied the chemotaxis of peripheral blood polymorphonuclear leukocytes (PMNs) and monocytes and the production of tumor necrosis factor alpha by monocytes of patients with juvenile periodontitis (JP). As a group, the patients' PMNs showed significantly increased chemotaxis determined by counting the number of migrating cells within a 3-microns-pore-size filter. Determined as distance of migration within the filter, as chemotactic increment based on checkerboard analysis, as leukotactic index calculated on the basis of distance of migration and cell count at different depths within a 3-microns-pore-size filter, as distance of migration under agarose, and as the number of PMNs migrating across a 5-microns-pore-size filter, the chemotactic migration rates of PMNs of patients were similar to those of controls. Evaluation of the data on an individual basis suggested that in terms of PMN chemotaxis some patients were hyperresponsive and some were hyporesponsive. Chemotaxis, spontaneous migration, and the rates of lipopolysaccharide-induced tumor necrosis factor alpha production by JP monocytes were similar to those of control cells. Our results give credence to the view that there are minor aberrations in the functions of JP phagocytes, but the extent to which these aberrations are relevant to accumulation of PMNs at sites of infection and inflammation in vivo and possibly contribute to the pathogenesis of JP remains unclear. PMID:2318531

  1. Juvenile fibromyalgia: Guidance for management.

    PubMed

    Yokota, Shumpei; Kikuchi, Masako; Miyamae, Takako

    2013-08-01

    Juvenile fibromyalgia (JFM) is a disease in which patients complain of acute and chronic severe pain, an overt primary cause for which cannot be found or surmised. Although patients with JFM mainly complain of systemic pain or allodynia in the medical interview and physical examination, the concept of the disease is the total sum of painful illness, chronic fatigue, hypothermia and many other autonomic symptoms and signs. Many issues are interacting including individual traits (personality, temperament, sensitivity, memory of pain; age: early adolescence), individual states (self-esteem, anxiety, developmental level), and external stressors (parent especially mother, school environment). JFM is diagnosed on the combination of disease history, physical examination to determine the 18 tender points and allodynia, pain from gently touching their hair, and negative results of blood tests (inflammatory markers, thyroid function, myogenic enzymes). The goals of treatment are the following: restoration of function and relief of pain. Psychological support is advocated. Although the exact number of patients with JFM is still to be elucidated, it seems to be growing because pediatric rheumatologists in Japan encounter children with a wide variety of musculoskeletal pains. This guideline describes how to diagnose JFM in children and how to treat them appropriately.

  2. Academic Achievement Among Juvenile Detainees

    PubMed Central

    Grigorenko, Elena L.; Macomber, Donna; Hart, Lesley; Naples, Adam; Chapman, John; Geib, Catherine F.; Chart, Hilary; Tan, Mei; Wolhendler, Baruch; Wagner, Richard

    2016-01-01

    The literature has long pointed to heightened frequencies of learning disabilities (LD) within the population of law offenders; however, a systematic appraisal of these observations, careful estimation of these frequencies, and investigation of their correlates and causes have been lacking. Here we present data collected from all youth (1,337 unique admissions, mean age 14.81, 20.3% females) placed in detention in Connecticut (January 1, 2010–July 1, 2011). All youth completed a computerized educational screener designed to test a range of performance in reading (word and text levels) and mathematics. A subsample (n = 410) received the Wide Range Achievement Test, in addition to the educational screener. Quantitative (scale-based) and qualitative (grade-equivalence-based) indicators were then analyzed for both assessments. Results established the range of LD in this sample from 13% to 40%, averaging 24.9%. This work provides a systematic exploration of the type and severity of word and text reading and mathematics skill deficiencies among juvenile detainees and builds the foundation for subsequent efforts that may link these deficiencies to both more formal, structured, and variable definitions and classifications of LD, and to other types of disabilities (e.g., intellectual disability) and developmental disorders (e.g., ADHD) that need to be conducted in future research. PMID:24064502

  3. Academic Achievement Among Juvenile Detainees.

    PubMed

    Grigorenko, Elena L; Macomber, Donna; Hart, Lesley; Naples, Adam; Chapman, John; Geib, Catherine F; Chart, Hilary; Tan, Mei; Wolhendler, Baruch; Wagner, Richard

    2015-01-01

    The literature has long pointed to heightened frequencies of learning disabilities (LD) within the population of law offenders; however, a systematic appraisal of these observations, careful estimation of these frequencies, and investigation of their correlates and causes have been lacking. Here we present data collected from all youth (1,337 unique admissions, mean age 14.81, 20.3% females) placed in detention in Connecticut (January 1, 2010-July 1, 2011). All youth completed a computerized educational screener designed to test a range of performance in reading (word and text levels) and mathematics. A subsample (n = 410) received the Wide Range Achievement Test, in addition to the educational screener. Quantitative (scale-based) and qualitative (grade-equivalence-based) indicators were then analyzed for both assessments. Results established the range of LD in this sample from 13% to 40%, averaging 24.9%. This work provides a systematic exploration of the type and severity of word and text reading and mathematics skill deficiencies among juvenile detainees and builds the foundation for subsequent efforts that may link these deficiencies to both more formal, structured, and variable definitions and classifications of LD, and to other types of disabilities (e.g., intellectual disability) and developmental disorders (e.g., ADHD) that need to be conducted in future research.

  4. Neurofibromin and Neuronal Apoptosis

    DTIC Science & Technology

    2005-07-01

    for these differences in the response of Nfl-/- neurons. "So What" Section. The learning disabilities associated with NF I constitute a highly variable...and +/+ neurons appear to become more significant with age. Our results may have implications for two areas: 1) the pathogenesis of learning ... disabilities in children with NF I, and 2) therapeutic strategies or targets for prolonging neuron survival, or for increasing neuronal response to protective

  5. 78 FR 65297 - Meeting of the Coordinating Council on Juvenile Justice and Delinquency Prevention

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-31

    ... JUVENILE JUSTICE AND DELINQUENCY PREVENTION Meeting of the Coordinating Council on Juvenile Justice and Delinquency Prevention AGENCY: Coordinating Council on Juvenile Justice and Delinquency Prevention. ACTION: Notice of meeting. SUMMARY: The Coordinating Council on Juvenile Justice and Delinquency...

  6. 77 FR 24687 - Meeting of the Coordinating Council on Juvenile Justice and Delinquency Prevention

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-25

    ... JUVENILE JUSTICE AND DELINQUENCY PREVENTION Meeting of the Coordinating Council on Juvenile Justice and Delinquency Prevention AGENCY: Coordinating Council on Juvenile Justice and Delinquency Prevention. ACTION: Notice of meeting. SUMMARY: The Coordinating Council on Juvenile Justice and Delinquency...

  7. 76 FR 39075 - Meeting of the Coordinating Council on Juvenile Justice and Delinquency Prevention

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-05

    ... JUVENILE JUSTICE AND DELINQUENCY PREVENTION Meeting of the Coordinating Council on Juvenile Justice and Delinquency Prevention AGENCY: Coordinating Council on Juvenile Justice and Delinquency Prevention. ACTION: Notice of meeting. SUMMARY: The Coordinating Council on Juvenile Justice and Delinquency...

  8. 76 FR 26280 - Meeting of the Coordinating Council on Juvenile Justice and Delinquency Prevention

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-06

    ... of the Office of Juvenile Justice and Delinquency Prevention (Vice Chair), the Secretary of Health... JUVENILE JUSTICE AND DELINQUENCY PREVENTION Meeting of the Coordinating Council on Juvenile Justice and Delinquency Prevention AGENCY: Coordinating Council on Juvenile Justice and Delinquency Prevention....

  9. 78 FR 58288 - Meeting of the Coordinating Council on Juvenile Justice and Delinquency Prevention

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-23

    ... JUVENILE JUSTICE AND DELINQUENCY PREVENTION Meeting of the Coordinating Council on Juvenile Justice and Delinquency Prevention AGENCY: Coordinating Council on Juvenile Justice and Delinquency Prevention. ACTION: Notice of meeting. SUMMARY: The Coordinating Council on Juvenile Justice and Delinquency...

  10. 78 FR 17184 - Meeting of the Coordinating Council on Juvenile Justice and Delinquency Prevention

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-20

    ... the Office of Juvenile Justice and Delinquency Prevention (Vice Chair), the Secretary of Health and... JUVENILE JUSTICE AND DELINQUENCY PREVENTION Meeting of the Coordinating Council on Juvenile Justice and Delinquency Prevention AGENCY: Coordinating Council on Juvenile Justice and Delinquency Prevention....

  11. The NG2 Protein Is Not Required for Glutamatergic Neuron-NG2 Cell Synaptic Signaling.

    PubMed

    Passlick, Stefan; Trotter, Jacqueline; Seifert, Gerald; Steinhäuser, Christian; Jabs, Ronald

    2016-01-01

    NG2 glial cells (as from now NG2 cells) are unique in receiving synaptic input from neurons. However, the components regulating formation and maintenance of these neuron-glia synapses remain elusive. The transmembrane protein NG2 has been considered a potential mediator of synapse formation and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) clustering, because it contains 2 extracellular Laminin G/Neurexin/Sex Hormone-Binding Globulin domains, which in neurons are crucial for formation of transsynaptic neuroligin-neurexin complexes. NG2 is connected via Glutamate Receptor-Interacting Protein with GluA2/3-containing AMPARs, thereby possibly mediating receptor clustering in glial postsynaptic density. To elucidate the role of NG2 in neuron-glia communication, we investigated glutamatergic synaptic transmission in juvenile and aged hippocampal NG2 cells of heterozygous and homozygous NG2 knockout mice. Neuron-NG2 cell synapses readily formed in the absence of NG2. Short-term plasticity, synaptic connectivity, postsynaptic AMPAR current kinetics, and density were not affected by NG2 deletion. During development, an NG2-independent acceleration of AMPAR current kinetics and decreased synaptic connectivity were observed. Our results indicate that the lack of NG2 does not interfere with genesis and basic properties of neuron-glia synapses. In addition, we demonstrate frequent expression of neuroligins 1-3 in juvenile and aged NG2 cells, suggesting a role of these molecules in synapse formation between NG2 glia and neurons.

  12. Neuronal network plasticity and recovery from depression.

    PubMed

    Castrén, Eero

    2013-09-01

    The brain processes sensory information in neuronal networks that are shaped by experience, particularly during early life, to optimally represent the internal and external milieu. Recent surprising findings have revealed that antidepressant drugs reactivate a window of juvenile-like plasticity in the adult cortex. When antidepressant-induced plasticity was combined with appropriate rehabilitation, it brought about a functional recovery of abnormally wired neuronal networks. These observations suggest that antidepressants act permissively to facilitate environmental influence on neuronal network reorganization and so provide a plausible neurobiological explanation for the enhanced effect of combining antidepressant treatment with psychotherapy. The results emphasize that pharmacological and psychological treatments of mood disorders are closely entwined: the effect of antidepressant-induced plasticity is facilitated by rehabilitation, such as psychotherapy, that guides the plastic networks, and psychotherapy benefits from the enhanced plasticity provided by the drug treatment. Optimized combinations of pharmacological and psychological treatments might help make best use of existing antidepressant drugs and reduce the number of treatment-resistant patients. The network hypothesis of antidepressant action presented here proposes that recovery from depression and related mood disorders is a gradual process that develops slowly and is facilitated by structured guidance and rehabilitation.

  13. Psychiatric and Medical Health Care Policies in Juvenile Detention Facilities

    ERIC Educational Resources Information Center

    Pajer, Kathleen A.; Kelleher, Kelly; Gupta, Ravindra A.; Rolls, Jennifer; Gardner, William

    2007-01-01

    A study aims to examine the existing health care policies in U.S. juvenile detention centres. The results conclude that juvenile detention facilities have many shortfalls in providing care for adolescents, particularly mental health care.

  14. SEASONAL VARIATION IN PLASMA SEX STEROID CONCENTRATION IN JUVENILE ALLIGATORS

    EPA Science Inventory

    Seasonal variation in plasma sex steroid concentrations is common in mature vertebrates, and is occasionally seen in juvenile animals. In this study, we examine the seasonal pattern of sex hormone concentration in juvenile American alligators (Alligator mississippiensis) and make...

  15. Psychiatric and Medical Health Care Policies in Juvenile Detention Facilities

    ERIC Educational Resources Information Center

    Pajer, Kathleen A.; Kelleher, Kelly; Gupta, Ravindra A.; Rolls, Jennifer; Gardner, William

    2007-01-01

    A study aims to examine the existing health care policies in U.S. juvenile detention centres. The results conclude that juvenile detention facilities have many shortfalls in providing care for adolescents, particularly mental health care.

  16. SEASONAL VARIATION IN PLASMA SEX STEROID CONCENTRATION IN JUVENILE ALLIGATORS

    EPA Science Inventory

    Seasonal variation in plasma sex steroid concentrations is common in mature vertebrates, and is occasionally seen in juvenile animals. In this study, we examine the seasonal pattern of sex hormone concentration in juvenile American alligators (Alligator mississippiensis) and make...

  17. Juvenile Fibromyalgia: A Multidisciplinary Approach to Treatment.

    PubMed

    Tesher, Melissa S

    2015-06-01

    A 14-year-old boy presented with months of severe widespread musculoskeletal pain. He was profoundly fatigued and unable to attend school. Laboratory evaluation, including complete blood count, comprehensive metabolic panel, inflammatory markers, and thyroid function, was unrevealing. Physical examination was also normal except for multiple tender points. The patient was diagnosed with juvenile primary fibromyalgia syndrome and referred for multidisciplinary treatment including physical therapy, exercise, and counseling, and his daily functioning gradually improves. Juvenile fibromyalgia is a complex syndrome that often severely limits patients' activities and can impede normal adolescent development. Effective treatment requires an understanding of the biologic, psychologic, and social factors contributing to the perpetuation of chronic pain. The author reviews the diagnostic criteria, pathophysiology, and treatment of juvenile fibromyalgia. Medications, particularly antidepressants and anticonvulsants, can be useful adjuncts to therapy. However, multimodal pain management including intensive physical therapy, exercise, counseling, and sleep hygiene is most effective in treating fibromyalgia.

  18. [Healthcare of imprisoned juveniles: new regulations].

    PubMed

    Sannier, O; Nappez, S; Manaouil, C

    2010-02-01

    Several new French regulations have come into effect to regulate the healthcare of juvenile offenders in prison with the creation of French Young Offender Institutions. They complete the French prison healthcare methodological guide. This article presents the new developments in the healthcare of juveniles in prison. It specifies the limitations placed on the healthcare team's interventions on imprisoned juveniles. Promoting an individualized prisoner program, as is done in the school context, outlining parental involvement in this program, and withdrawing from the healthcare methodological guide the tasks that are not within the realm of the physician caring for the minor would be measures to ensure good ethical medical practices in prison. These could be applied to French secure training centers and secure children's homes.

  19. Effect of TBT on Ruditapes decussatus juveniles.

    PubMed

    Coelho, M R; Langston, W J; Bebianno, M J

    2006-06-01

    The effects of sublethal concentrations of tributyltin (TBT) on growth of juvenile clams Ruditapes decussatus were determined during exposure to TBT concentrations of 50, 100 and 250 ng l(-1) (as Sn) for a period up to two years. Length and weight of clams increased continuously in all treatments throughout the experimental period, and, overall, rates were not significantly influenced by TBT exposure, although final length and weight were inversely related to increasing TBT concentration. Juvenile R. decussatus therefore appear to be less sensitive to TBT than larval stages. Some juveniles exposed to TBT developed abnormal shell growth, laterally, changing the typical flattened shape of clams into a more "rounded" form. This characteristic was more visible in the anterior margins of valves than posteriorly, and mainly observed in clams exposed to TBT at 50 ng l(-1) (as Sn).

  20. An unusual presentation of juvenile Alexander disease.

    PubMed

    Osorio, Maria Joana; Risen, Sarah; Alper, Gulay

    2012-04-01

    Alexander disease is a rare leukodystrophy that most often presents in infancy but also includes neonatal, juvenile, and adult variants. Juvenile Alexander disease presents primarily with bulbar symptoms between 2 and 12 years of age. The diagnosis is often suggested by the clinical course and brain magnetic resonance image pattern and then confirmed by the presence of a mutation in the glial fibrillary acidic protein gene. A young girl presented with globus sensation and magnetic resonance imaging of the brain revealed abnormalities mainly involving white matter tracts of the medulla oblongata and cerebellum. The presence of a mutation in the glial fibrillary acidic protein gene confirmed the diagnosis of juvenile Alexander disease. A high index of clinical suspicion is necessary for the diagnosis of late-onset presentations of Alexander disease.

  1. The pathophysiology of the juvenile bunion.

    PubMed

    Coughlin, M J; Mann, R A

    1987-01-01

    While the surgeon may tend to use one procedure in the repair of a hallux valgus deformity, versatility is most important when treating the juvenile bunion. Using a distal soft-tissue repair when subluxation is solely at the metatarsophalangeal joint is an acceptable approach. A metatarsal or cuneiform osteotomy is necessary if the intermetatarsal angle is abnormally large. It is important not to stretch the indications for a bunion technique in order to correct the hallux valgus deformity. If a more severe deformity is present, a more aggressive technique must be used to correct the abnormality. That varying success rates are reported with different techniques testifies to the fact that the juvenile bunion is not suited for a standard hallux valgus repair. The surgical technique used to repair a specific juvenile bunion depends upon the anatomic and physiologic abnormalities present in each patient.

  2. Corporal and capital punishment of juveniles.

    PubMed

    Frazier, H C

    1990-01-01

    There is a previously unobserved connection between corporal punishment of public school children and capital punishment of juveniles. Both are barometers of acceptable levels of violent punishment and their elimination is a hallmark of a maturing and decent society. Within a majority of the eighteen states where school authorities most frequently strike children are housed 25 of the nation's 28 juvenile death row inmates. On average, the homicide rates of these jurisdictions are two and a half times greater than those that have abolished both state-sanctioned corporal and capital punishment or limit death sentences to those age eighteen and older at the time of their crime(s). Most of the eighteen state abolitions of corporal punishment occurred in the 1980's. The US Supreme Court has ruled both corporal and capital punishment of juveniles constitutional. Additional state legislative abolition of both is anticipated in the 1990s.

  3. Modern management of juvenile recurrent parotitis.

    PubMed

    Capaccio, P; Sigismund, P E; Luca, N; Marchisio, P; Pignataro, L

    2012-12-01

    To evaluate modern diagnostic and therapeutic management of juvenile recurrent parotitis, and to show the benefits of operative sialoendoscopy on the basis of our experience in 14 patients and the results of others. Ultrasonography is sensitive in detecting the pathological features of juvenile recurrent parotitis. Interventional sialoendoscopy is a safe and effective method of treating the disease. In our case series, after a mean follow-up time of 30 months only 5 patients experienced recurrence of symptoms, with a mean symptom-free period of 20 months. The use of modern, minimally invasive diagnostic tools such as colour Doppler ultrasonography, magnetic resonance sialography and sialoendoscopy represents a new frontier in the management of juvenile recurrent parotitis. Operative sialoendoscopy also has the important therapeutic benefit of reducing the number of recurrences of acute episodes of parotitis, thus giving patients a better quality of life until puberty.

  4. Juvenile age estimation from facial images.

    PubMed

    Ferguson, Eilidh; Wilkinson, Caroline

    2017-01-01

    Age determination from images can be of vital importance, particularly in cases involving suspected child sexual abuse (CSA). It is imperative to determine if an individual depicted in such an image is indeed a child, with a more concise age often sought, as this may affect the severity of offender sentencing. The aims of this study were to establish the accuracy of visual age estimation of the juvenile face in children aged between 0 and 16years and to determine if varying levels of exposure to children affected an individual's ability to assess age from the face. An online questionnaire consisting of 30 juvenile face images was created using SurveyMonkey®. The overall results suggested poor accuracy for visual age estimation of juvenile faces. The age, sex, occupation and number of children of the participants did not affect the ability to estimate age from facial images. Similarly, the sex and age of the juvenile faces did not appear to affect the accuracy of age estimation. When specific age groups are considered, sex may have an influence on age estimation, with female faces being aged more accurately in the younger age groups and male faces more accurate after the age of 11years, however this is based on a small sample. This study suggests that the accuracy of juvenile age estimation from the face alone is poor using simple visual assessment of images. Further research is required to determine exactly how age is assessed from a facial image, if there are indicators, or features in particular that lead to over- or under-estimation of juvenile age.

  5. Dendritic branching angles of pyramidal cells across layers of the juvenile rat somatosensory cortex.

    PubMed

    Leguey, Ignacio; Bielza, Concha; Larrañaga, Pedro; Kastanauskaite, Asta; Rojo, Concepción; Benavides-Piccione, Ruth; DeFelipe, Javier

    2016-09-01

    The characterization of the structural design of cortical microcircuits is essential for understanding how they contribute to function in both health and disease. Since pyramidal neurons represent the most abundant neuronal type and their dendritic spines constitute the major postsynaptic elements of cortical excitatory synapses, our understanding of the synaptic organization of the neocortex largely depends on the available knowledge regarding the structure of pyramidal cells. Previous studies have identified several apparently common rules in dendritic geometry. We study the dendritic branching angles of pyramidal cells across layers to further shed light on the principles that determine the geometric shapes of these cells. We find that the dendritic branching angles of pyramidal cells from layers II-VI of the juvenile rat somatosensory cortex suggest common design principles, despite the particular morphological and functional features that are characteristic of pyramidal cells in each cortical layer. J. Comp. Neurol. 524:2567-2576, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Sphingomyelin lipidosis (Niemann-Pick disease) in a juvenile raccoon (Procyon lotor).

    PubMed

    Vapniarsky, N; Wenger, D A; Scheenstra, D; Mete, A

    2013-01-01

    A wild caught juvenile male raccoon with neurological disease was humanely destroyed due to poor prognosis. Necropsy examination revealed hepatomegaly, splenomegaly and multicentric lymphadenomegaly with diffuse hepatic pallor and pulmonary consolidation with pinpoint pale subpleural foci. Microscopically, there was marked pale cytoplasmic swelling of the central and peripheral neurons as well as the glial cells in the brain, accompanied by multiorgan infiltration by abundant foamy macrophages. Ultrastructural investigation revealed accumulation of concentrically arranged lamellar material within lysosomes of the affected neurons, macrophages and endothelial cells. Biochemical enzymatic analysis detected sphingomyelinase deficiency and lysosomal storage disease consistent with sphingomyelin lipidosis (Niemann-Pick disease [NPD]) was diagnosed. This is the first report of NPD in a raccoon.

  7. Immunohistochemical insights into Saffold virus infection of the brain of juvenile AG129 mice.

    PubMed

    Tan, Shawn Zheng Kai; Prabakaran, Mookkan

    2016-11-25

    Saffold Virus (SAFV) is a human cardiovirus that is suspected of causing infection of the central nervous system (CNS) in children. While recent animal studies have started to elucidate the pathogenesis of SAFV, very little is known about the mechanisms behind it. In this study, we attempted to elucidate some of the mechanisms of the pathogenesis of SAFV in the brain of a juvenile mouse model by using immunohistochemical methods. We first showed that SAFV is able to infect both neuronal and glial cells in the brain of 2 week-old AG129 mice. We then showed that SAFV is able to induce apoptosis in both neuronal and glial cells in the brain. Lastly, we showed that SAFV infection does not show any signs of gross demyelination in the brain. Overall, our results provide important insights into the mechanisms of SAFV in the brain.

  8. Juvenile dermatomyositis in a Nigerian girl.

    PubMed

    Adelowo, Olufemi; Nwankwo, Madu; Olaosebikan, Hakeem

    2014-04-04

    Juvenile dermatomyositis is an autoimmune connective tissue disease occurring in children less than 16 years old. It is part of a heterogeneous group of muscle diseases called idiopathic Iiflammatory myopathies. It had previously been reported in black Africans resident in UK. However, there is no documented case reported from Africa. The index sign of heliotrope rashes is often difficult to visualise in the black skin. An 11-year-old Nigerian girl presenting with clinical, laboratory and histopathological features of juvenile dermatomyositis is presented here. It is hoped that this case will heighten the index of suspicion of this condition among medical practitioners in Africa.

  9. Moulting tail feathers in a juvenile oviraptorisaur.

    PubMed

    Prum, Richard O

    2010-11-04

    Xu et al. describe the extraordinarily preserved feathers from two subadults of the oviraptorisaur Similicaudipteryx from the Yixian Formation of Liaoning, China. The preserved tail feathers of the juvenile specimen (STM4.1) show a morphology not previously observed in any fossil feathers. The tail feathers of an older, immature specimen (STM22-6) show a typical closed pennaceous structure with a prominent, planar vane. I propose that the feathers of the tail of the juvenile specimen are not a specialized feather generation, but fossilized 'pin feathers' or developing feather germs.

  10. Juvenile probation officers' mental health decision making.

    PubMed

    Wasserman, Gail A; McReynolds, Larkin S; Whited, Andria L; Keating, Joseph M; Musabegovic, Hana; Huo, Yanling

    2008-09-01

    We reviewed case records for 583 juvenile delinquency intakes in four county juvenile probation offices; 14.4% were receiving mental health or substance use services at case opening, and 24.9% were newly identified during probation contact. Youths were significantly more likely to be newly identified if they were repeat offenders, if their probation officer knew more about mental health and if they resided in a county without a shortage of available mental health professionals. Probation officers were especially likely to underidentify internalizing disorders. Policy implications for promoting identification of mental health needs and improving linkage to community service providers are discussed.

  11. The World of Juvenile Justice According to the Numbers

    ERIC Educational Resources Information Center

    Rozalski, Michael; Deignan, Marilyn; Engel, Suzanne

    2008-01-01

    Intended to be an instructive, yet sobering, introduction to the complex and disturbing nature of the juvenile justice system, this article details the "numbers," including selected percentages, ratios, and dollar amounts, that are relevant to developing a better understanding of the juvenile justice system. General statistics about juvenile and…

  12. Programa Shortstop: A Culturally Focused Juvenile Intervention for Hispanic Youth

    ERIC Educational Resources Information Center

    Cervantes, Richard C.; Ruan, Karen; Duenas, Norma

    2004-01-01

    Culturally sensitive juvenile delinquency and substance abuse interventions are relatively limited and unavailable to many first-time Hispanic juvenile offenders. The purpose of this study was to test the effectiveness of a culturally focused juvenile and substance abuse intervention program for first time Hispanic youth offenders. The intent of…

  13. Public Schools and the Juvenile Justice System: Facilitating Relationships

    ERIC Educational Resources Information Center

    Mazzotti, Valerie L.; Higgins, Kyle

    2006-01-01

    This article describes the importance of facilitating relationships between schools and the Juvenile Justice System. Emphasis is placed on statistics concerning children/youth involved in the Juvenile Justice System and the current state of school programs. Strategies for developing integrated programs between schools and the Juvenile Justice…

  14. Contagion and Repeat Offending among Urban Juvenile Delinquents

    ERIC Educational Resources Information Center

    Mennis, Jeremy; Harris, Philip

    2011-01-01

    This research investigates the role of repeat offending and spatial contagion in juvenile delinquency recidivism using a database of 7166 male juvenile offenders sent to community-based programs by the Family Court of Philadelphia. Results indicate evidence of repeat offending among juvenile delinquents, particularly for drug offenders. The…

  15. American Youth Violence: Implications for National Juvenile Justice Policy.

    ERIC Educational Resources Information Center

    Zimring, Franklin E.

    2000-01-01

    Argues that the perception of increasing youth violence is based on fiction rather than fact. Provides the facts involved in the juvenile justice policy focusing on the differences between juvenile and adult violence, youth violence trends, population trends, and three legal policy issues toward adolescent violence. Offers juvenile crime…

  16. Juveniles in Adult Jails and Lockups: It's Your Move.

    ERIC Educational Resources Information Center

    Illinois Univ., Champaign. Community Research Center.

    Issues relevant to juveniles in adult jails are discussed in this guide which is designed to aid concerned citizens who want to promote public interest and support for the removal of juveniles from adult jails and lockups. Statistics on the number of juveniles in adult jails, their ages, seriousness of offenses, and suicide rate are given. The…

  17. Juvenile Justice and Public Policy: Toward a National Agenda.

    ERIC Educational Resources Information Center

    Schwartz, Ira M., Ed.

    Some of the most critical and troubling issues in juvenile justice are addressed to serve as a catalyst and resource for developing sound juvenile justice public policy decisions. The following chapters examine juvenile court policies, special issues, and cost-effective interventions, and present findings of a national survey of public attitudes…

  18. Best Practices in Juvenile Accountability: Overview. JAIBG Bulletin.

    ERIC Educational Resources Information Center

    Beyer, Marty

    This bulletin examines the Office of Juvenile Justice and Delinquency Prevention's Juvenile Accountability Incentive Block Grants (JAIBG) program, which asserts that juvenile offenders should be held accountable for their crimes as a matter of basic justice and to prevent and deter delinquency. It reviews the developmental perspective shaping…

  19. Mental Health Implications of the Juvenile Justice Standards.

    ERIC Educational Resources Information Center

    Morse, Stephen J.; Whitebread, Charles H., II

    1982-01-01

    The Juvenile Justice Standards developed by the Institute of Judicial Administration and the American Bar Association reflect a trend away from the therapeutic aspect of the juvenile court and toward due process for juveniles accused of delinquent offenses. (Author/MJL)

  20. Chronic Juvenile Delinquency and the "Suppression Effect": An Exploratory Study.

    ERIC Educational Resources Information Center

    Fraser, Mark; Norman, Michael

    1988-01-01

    Notes that fear of apprehension and punishment have been reported to suppress juvenile crime. Discusses suppression effect in regard to the correlates of chronic juvenile delinquency and exploratory evidence that youth who commit large volume of crime do not fear sanctions imposed by juvenile court any more than youth who commit only one offense…

  1. Race, Legal Representation, and Juvenile Justice: Issues and Concerns

    ERIC Educational Resources Information Center

    Guevara, Lori; Spohn, Cassia; Herz, Denise

    2004-01-01

    The objective of this study was to examine the influence of type of counsel across race on juvenile court outcomes. Using data from a sample of juvenile court referrals from two midwestern juvenile courts, this study examined the interaction of race and type of counsel on disposition outcome. The results indicated that youth without an attorney…

  2. Programa Shortstop: A Culturally Focused Juvenile Intervention for Hispanic Youth

    ERIC Educational Resources Information Center

    Cervantes, Richard C.; Ruan, Karen; Duenas, Norma

    2004-01-01

    Culturally sensitive juvenile delinquency and substance abuse interventions are relatively limited and unavailable to many first-time Hispanic juvenile offenders. The purpose of this study was to test the effectiveness of a culturally focused juvenile and substance abuse intervention program for first time Hispanic youth offenders. The intent of…

  3. Resiliency Scales for Children and Adolescents: Profiles of Juvenile Offenders

    ERIC Educational Resources Information Center

    Mowder, Melissa H.; Cummings, Jack A.; McKinney, Robert

    2010-01-01

    An exploratory study of resiliency profiles of male and female juvenile offenders committed to a juvenile correctional facility was conducted. The goal of the present study was to examine juvenile offenders' positive characteristics (e.g., adaptability, optimism, self-efficacy, tolerance of differences). To assess positive characteristics and…

  4. 28 CFR 0.57 - Criminal prosecutions against juveniles.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... supervises the implementation of the Juvenile Justice and Delinquency Prevention Act (18 U.S.C. 5031 et seq.). ... 28 Judicial Administration 1 2011-07-01 2011-07-01 false Criminal prosecutions against juveniles... JUSTICE Criminal Division § 0.57 Criminal prosecutions against juveniles. The Assistant Attorney...

  5. 28 CFR 0.57 - Criminal prosecutions against juveniles.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... supervises the implementation of the Juvenile Justice and Delinquency Prevention Act (18 U.S.C. 5031 et seq.). ... 28 Judicial Administration 1 2012-07-01 2012-07-01 false Criminal prosecutions against juveniles... JUSTICE Criminal Division § 0.57 Criminal prosecutions against juveniles. The Assistant Attorney...

  6. 28 CFR 0.57 - Criminal prosecutions against juveniles.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... supervises the implementation of the Juvenile Justice and Delinquency Prevention Act (18 U.S.C. 5031 et seq.). ... 28 Judicial Administration 1 2014-07-01 2014-07-01 false Criminal prosecutions against juveniles... JUSTICE Criminal Division § 0.57 Criminal prosecutions against juveniles. The Assistant Attorney...

  7. 28 CFR 0.57 - Criminal prosecutions against juveniles.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... supervises the implementation of the Juvenile Justice and Delinquency Prevention Act (18 U.S.C. 5031 et seq.). ... 28 Judicial Administration 1 2013-07-01 2013-07-01 false Criminal prosecutions against juveniles... JUSTICE Criminal Division § 0.57 Criminal prosecutions against juveniles. The Assistant Attorney...

  8. Resiliency Scales for Children and Adolescents: Profiles of Juvenile Offenders

    ERIC Educational Resources Information Center

    Mowder, Melissa H.; Cummings, Jack A.; McKinney, Robert

    2010-01-01

    An exploratory study of resiliency profiles of male and female juvenile offenders committed to a juvenile correctional facility was conducted. The goal of the present study was to examine juvenile offenders' positive characteristics (e.g., adaptability, optimism, self-efficacy, tolerance of differences). To assess positive characteristics and…

  9. Race, Legal Representation, and Juvenile Justice: Issues and Concerns

    ERIC Educational Resources Information Center

    Guevara, Lori; Spohn, Cassia; Herz, Denise

    2004-01-01

    The objective of this study was to examine the influence of type of counsel across race on juvenile court outcomes. Using data from a sample of juvenile court referrals from two midwestern juvenile courts, this study examined the interaction of race and type of counsel on disposition outcome. The results indicated that youth without an attorney…

  10. The Problems and Needs of Juvenile Court Wards in Oregon.

    ERIC Educational Resources Information Center

    Heuser, James Paul

    This document is an assessment of the service needs of one state's juvenile court wards written by a group of representatives of private and governmental agencies involved in working with children in the juvenile justice system. The group's goals were to generate accurate program and fiscal information about the juvenile justice and juvenile…

  11. Second Analysis and Evaluation: Federal Juvenile Delinquency Programs. Volume I.

    ERIC Educational Resources Information Center

    National Inst. for Juvenile Justice and Delinquency Prevention (Dept. of Justice/LEAA), Washington, DC.

    This document expands and updates the information presented in the First Analysis and Evaluation of Federal Juvenile Delinquency Programs. It includes: a description of the Office of Juvenile Justice and Delinquency Prevention and the National Institute for Juvenile Justice and Delinquency Prevention; a report on the activities and recommendations…

  12. Juvenile Recidivism: A Comparison of Three Prediction Instruments.

    ERIC Educational Resources Information Center

    Ashford, Jose B.; LeCroy, Craig Winston

    1990-01-01

    Compared three models to predict recidivism in juvenile offenders. Discriminant analyses performed on data from 91 juvenile parolees (42 nonrecidivists, 49 recidivists) revealed that Orange County Risk Assessment Instrument and Arizona Juvenile Risk Assessment Form were able to predict recidivism 18-22 percent better than chance. Contra Costa Risk…

  13. The World of Juvenile Justice According to the Numbers

    ERIC Educational Resources Information Center

    Rozalski, Michael; Deignan, Marilyn; Engel, Suzanne

    2008-01-01

    Intended to be an instructive, yet sobering, introduction to the complex and disturbing nature of the juvenile justice system, this article details the "numbers," including selected percentages, ratios, and dollar amounts, that are relevant to developing a better understanding of the juvenile justice system. General statistics about juvenile and…

  14. It's Your Move: Juveniles in Adult Jails and Lockups.

    ERIC Educational Resources Information Center

    Illinois Univ., Champaign. Community Research Center.

    This booklet discusses the confinement of juveniles in adult jails, and offers suggestions for local citizens who want to remedy the problem. The first section presents background information on juveniles in adult jails, and discusses the following issues: the physically and psychologically damaging effects on juveniles of incarceration in adult…

  15. Contagion and Repeat Offending among Urban Juvenile Delinquents

    ERIC Educational Resources Information Center

    Mennis, Jeremy; Harris, Philip

    2011-01-01

    This research investigates the role of repeat offending and spatial contagion in juvenile delinquency recidivism using a database of 7166 male juvenile offenders sent to community-based programs by the Family Court of Philadelphia. Results indicate evidence of repeat offending among juvenile delinquents, particularly for drug offenders. The…

  16. Conditions of Confinement: Juvenile Detention and Corrections Facilities. Research Summary.

    ERIC Educational Resources Information Center

    Parent, Dale G.; And Others

    The most comprehensive nationwide research ever conducted on the juvenile detention and corrections field was a study by the Office of Juvenile Justice and Delinquency Prevention (OJJDP) assessing conditions of confinement for juveniles and determining the extent to which those conditions conform to recognized national professional standards. The…

  17. Lateralization of the connections of the ovary to the celiac ganglia in juvenile rats

    PubMed Central

    Morán, Carolina; Zarate, Fabiola; Morán, José Luis; Handal, Anabella; Domínguez, Roberto

    2009-01-01

    During the development of the female rat, a maturing process of the factors that regulate the functioning of the ovaries takes place, resulting in different responses according to the age of the animal. Studies show that peripheral innervation is one relevant factor involved. In the present study we analyzed the anatomical relationship between the neurons in the celiac-superior mesenteric ganglia (CSMG), and the right or left ovary in 24 or 28 days old female pre-pubertal rats. The participation of the superior ovarian nerve (SON) in the communication between the CSMG and the ovaries was analyzed in animals with unilateral section of the SON, previous to injecting true blue (TB) into the ovarian bursa. The animals were killed seven days after treatment. TB stained neurons were quantified at the superior mesenteric-celiac ganglia. The number of labeled neurons in the CSMG of rats treated at 28 days of age was significantly higher than those treated on day 24. At age 24 days, injecting TB into the right ovary resulted in neuron stains on both sides of the celiac ganglia; whereas, injecting the left side the stains were exclusively ipsilateral. Such asymmetry was not observed when the rats were treated at age of 28 days. In younger rats, sectioning the left SON resulted in significantly lower number of stained neurons in the left ganglia while sectioning the right SON did not modify the number of stained neurons. When sectioning of the SON was performed to 28 days old rats, no staining was observed. Present results show that the number and connectivity of post-ganglionic neurons of the CSMG connected to the ovary of juvenile female rats change as the animal mature; that the SON plays a role in this communication process as puberty approaches; and that this maturing process is different for the right or the left ovary. PMID:19460167

  18. Cajal bodies in neurons.

    PubMed

    Lafarga, Miguel; Tapia, Olga; Romero, Ana M; Berciano, Maria T

    2016-09-14

    Cajal is commonly regarded as the father of modern neuroscience in recognition of his fundamental work on the structure of the nervous system. But Cajal also made seminal contributions to the knowledge of nuclear structure in the early 1900s, including the discovery of the "accessory body" later renamed "Cajal body" (CB). This important nuclear structure has emerged as a center for the assembly of ribonucleoproteins (RNPs) required for splicing, ribosome biogenesis and telomere maintenance. The modern era of CB research started in the 1990s with the discovery of coilin, now known as a scaffold protein of CBs, and specific probes for small nuclear RNAs (snRNAs). In this review, we summarize what we have learned in the recent decades concerning CBs in post-mitotic neurons, thereby ruling out dynamic changes in CB functions during the cell cycle. We show that CBs are particularly prominent in neurons, where they frequently associate with the nucleolus. Neuronal CBs are transcription-dependent nuclear organelles. Indeed, their number dynamically accommodates to support the high neuronal demand for splicing and ribosome biogenesis required for sustaining metabolic and bioelectrical activity. Mature neurons have canonical CBs enriched in coilin, survival motor neuron protein and snRNPs. Disruption and loss of neuronal CBs associate with severe neuronal dysfunctions in several neurological disorders such as motor neuron diseases. In particular, CB depletion in motor neurons seems to reflect a perturbation of transcription and splicing in spinal muscular atrophy, the most common genetic cause of infant mortality.

  19. The challenges of the first migration: movement and behaviour of juvenile vs. adult white storks with insights regarding juvenile mortality.

    PubMed

    Rotics, Shay; Kaatz, Michael; Resheff, Yehezkel S; Turjeman, Sondra Feldman; Zurell, Damaris; Sapir, Nir; Eggers, Ute; Flack, Andrea; Fiedler, Wolfgang; Jeltsch, Florian; Wikelski, Martin; Nathan, Ran

    2016-07-01

    Migration conveys an immense challenge, especially for juvenile birds coping with enduring and risky journeys shortly after fledging. Accordingly, juveniles exhibit considerably lower survival rates compared to adults, particularly during migration. Juvenile white storks (Ciconia ciconia), which are known to rely on adults during their first fall migration presumably for navigational purposes, also display much lower annual survival than adults. Using detailed GPS and body acceleration data, we examined the patterns and potential causes of age-related differences in fall migration properties of white storks by comparing first-year juveniles and adults. We compared juvenile and adult parameters of movement, behaviour and energy expenditure (estimated from overall dynamic body acceleration) and placed this in the context of the juveniles' lower survival rate. Juveniles used flapping flight vs. soaring flight 23% more than adults and were estimated to expend 14% more energy during flight. Juveniles did not compensate for their higher flight costs by increased refuelling or resting during migration. When juveniles and adults migrated together in the same flock, the juvenile flew mostly behind the adult and was left behind when they separated. Juveniles showed greater improvement in flight efficiency throughout migration compared to adults which appears crucial because juveniles exhibiting higher flight costs suffered increased mortality. Our findings demonstrate the conflict between the juveniles' inferior flight skills and their urge to keep up with mixed adult-juvenile flocks. We suggest that increased flight costs are an important proximate cause of juvenile mortality in white storks and likely in other soaring migrants and that natural selection is operating on juvenile variation in flight efficiency.

  20. Vocal experimentation in the juvenile songbird requires a basal ganglia circuit.

    PubMed

    Olveczky, Bence P; Andalman, Aaron S; Fee, Michale S

    2005-05-01

    Songbirds learn their songs by trial-and-error experimentation, producing highly variable vocal output as juveniles. By comparing their own sounds to the song of a tutor, young songbirds gradually converge to a stable song that can be a remarkably good copy of the tutor song. Here we show that vocal variability in the learning songbird is induced by a basal-ganglia-related circuit, the output of which projects to the motor pathway via the lateral magnocellular nucleus of the nidopallium (LMAN). We found that pharmacological inactivation of LMAN dramatically reduced acoustic and sequence variability in the songs of juvenile zebra finches, doing so in a rapid and reversible manner. In addition, recordings from LMAN neurons projecting to the motor pathway revealed highly variable spiking activity across song renditions, showing that LMAN may act as a source of variability. Lastly, pharmacological blockade of synaptic inputs from LMAN to its target premotor area also reduced song variability. Our results establish that, in the juvenile songbird, the exploratory motor behavior required to learn a complex motor sequence is dependent on a dedicated neural circuit homologous to cortico-basal ganglia circuits in mammals.

  1. Criminal Profiles of Violent Juvenile Sex and Violent Juvenile Non-Sex Offenders: An Explorative Longitudinal Study

    ERIC Educational Resources Information Center

    van Wijk, Anton Ph.; Mali, Bas R. F.; Bullens, Ruud A. R.; Vermeiren, Robert R.

    2007-01-01

    Few studies have longitudinally investigated the criminal profiles of violent juvenile sex and violent juvenile non-sex offenders. To make up for this lack, this study used police records of juveniles to determine the nature of the criminal profiles of violent sex offenders (n = 226) and violent non-sex offenders (n = 4,130). All offenders…

  2. Juvenile Residential Facility Census, 2010: Selected Findings. Juvenile Offenders and Victims: National Report Series. Bulletin NCJ 241134

    ERIC Educational Resources Information Center

    Hockenberry, Sarah; Sickmund, Melissa; Sladky, Anthony

    2013-01-01

    This bulletin is part of the "Juvenile Offenders and Victims National Report Series." The "National Report" offers a comprehensive statistical overview of the problems of juvenile crime, violence, and victimization and the response of the juvenile justice system. During each interim year, the bulletins in the "National…

  3. Juvenile wood effect in red alder : analysis of physical and mechanical data to delineate juvenile and mature wood zones

    Treesearch

    Joel W. Evans; John F. Senft; David W. Green

    2000-01-01

    The objective of this study was to investigate the influence of juvenile wood on the mechanical and physical properties of red alder. Tree growth in the first 10 to 20 years, usually referred to as juvenile wood, often influences wood quality by adversely affecting mechanical strength properties. Strength can be reduced up to 50 percent by the presence of juvenile wood...

  4. Criminal Profiles of Violent Juvenile Sex and Violent Juvenile Non-Sex Offenders: An Explorative Longitudinal Study

    ERIC Educational Resources Information Center

    van Wijk, Anton Ph.; Mali, Bas R. F.; Bullens, Ruud A. R.; Vermeiren, Robert R.

    2007-01-01

    Few studies have longitudinally investigated the criminal profiles of violent juvenile sex and violent juvenile non-sex offenders. To make up for this lack, this study used police records of juveniles to determine the nature of the criminal profiles of violent sex offenders (n = 226) and violent non-sex offenders (n = 4,130). All offenders…

  5. Juvenile penalty or leniency: Sentencing of juveniles in the criminal justice system.

    PubMed

    Jordan, Kareem L; McNeal, Brittani A

    2016-08-01

    The purpose of this study is to examine the impact of being juvenile on sentencing in the criminal justice system. More specifically, youth transferred to criminal court are compared to adults in terms of likelihood of incarceration, jail length, and prison length. In this study, 2 national data sets are merged. The juvenile sample includes 3,381 convicted offenders, and the adult sample is comprised of 6,529 convicted offenders. The final sample is 9,910 offenders across 36 U.S. counties. The key independent variable is juvenile status, and the dependent variables are incarceration, jail length, and prison length. Because of the multilevel nature of the data, hierarchical linear modeling is used across all models. Juveniles are punished less severely in the jail incarceration decision. However, when youth are actually sentenced to incarceration (either jail or prison), they are given longer confinement time than adults. (PsycINFO Database Record

  6. Refinement of Neuronal Synchronization with Gamma Oscillations in the Medial Prefrontal Cortex after Adolescence

    PubMed Central

    de Almeida, Julián; Jourdan, Iván; Murer, Mario Gustavo; Belforte, Juan E.

    2013-01-01

    The marked anatomical and functional changes taking place in the medial prefrontal cortex (PFC) during adolescence set grounds for the high incidence of neuropsychiatric disorders with adolescent onset. Although circuit refinement through synapse pruning may constitute the anatomical basis for the cognitive differences reported between adolescents and adults, a physiological correlate of circuit refinement at the level of neuronal ensembles has not been demonstrated. We have recorded neuronal activity together with local field potentials in the medial PFC of juvenile and adult mice under anesthesia, which allowed studying local functional connectivity without behavioral or sensorial interference. Entrainment of pyramidal neurons and interneurons to gamma oscillations, but not to theta or beta oscillations, was reduced after adolescence. Interneurons were synchronized to gamma oscillations across a wider area of the PFC than pyramidal neurons, and the span of interneuron synchronization was shorter in adults than juvenile mice. Thus, transition from childhood to adulthood is characterized by reduction of the strength and span of neuronal synchronization specific to gamma oscillations in the mPFC. The more restricted and weak ongoing synchronization in adults may allow a more dynamic rearrangement of neuronal ensembles during behavior and promote parallel processing of information. PMID:23646166

  7. Neurofibromin and Neuronal Apoptosis

    DTIC Science & Technology

    2006-07-01

    role of familial pheochromocytoma genes, including succinate dehydrogenase (SDH) and Nf1, in modulating neuronal apoptosis following neurotrophin...gene products, in Nf1-/- sensory and sympathetic neurons; this work will also have relevance to the biology of familial pheochromocytoma . "So what...Schlisio, S. (2005). Neuronal apoptosis linked to EglN3 prolyl hydroxylase and familial pheochromocytoma genes: Developmental culling and cancer. Cancer

  8. Neurons and tumor suppressors.

    PubMed

    Zochodne, Douglas W

    2014-08-20

    Neurons choose growth pathways with half hearted reluctance, behavior that may be appropriate to maintain fixed long lasting connections but not to regenerate them. We now recognize that intrinsic brakes on regrowth are widely expressed in these hesitant neurons and include classical tumor suppressor molecules. Here, we review how two brakes, PTEN (phosphatase and tensin homolog deleted on chromosome 10) and retinoblastoma emerge as new and exciting knockdown targets to enhance neuron plasticity and improve outcome from damage or disease.

  9. Intervening with Convicted Serious Juvenile Offenders.

    ERIC Educational Resources Information Center

    Mann, Dale

    Juveniles who commit such serious offenses as nonnegligent homicide, rape, assault, and robbery constitute an increasing concern for the criminal justice system. Persons who commit these offenses force a balancing of conflicting demands for offender rehabilitation and community protection. This report, the result of a comprehensive effort…

  10. Juvenile Sex Offenders: Development and Correction.

    ERIC Educational Resources Information Center

    Ryan, Gail; And Others

    1987-01-01

    Three case histories elucidate a discussion of the developmental nature of the behaviors of juvenile male sexual offenders. The sexual assault cycle is defined in the stages of negative self-image, predicting rejection, isolation, fantasies, planning the offense, and committing the offense. Tools for treating the offender are outlined. (Author/JDD)

  11. Juvenile Offenders and Victims: A National Report.

    ERIC Educational Resources Information Center

    Snyder, Howard N.; Sickmund, Melissa

    Consolidating the most requested information on juvenile offenders and victims in the United States, this report presents statistical data in a user friendly format. The report is designed as a series of briefing papers on specific topics and contains short sections designed to be read in isolation from other parts of the report. The report is…

  12. Costs of Juvenile Violence: Policy Implications.

    ERIC Educational Resources Information Center

    Miller, Ted; Fisher, Deborah A.; Cohen, Mark A.

    2001-01-01

    Investigated the magnitude of juvenile violence in Pennsylvania in terms of victimization and perpetration. Used archival data on violent crimes in Pennsylvania during 1993 to develop cost estimates reflecting the costs incurred by society for both victims and perpetrators. Overall, violence against children and adolescents proved to be a much…

  13. Rehabilitation of the Personality of Juvenile Offenders

    ERIC Educational Resources Information Center

    Zaitsev, G. K.; Zaitsev, A. G.; Dmitriev, M. G.; Apal'kova, I. Iu.

    2009-01-01

    Russian youth has in recent years been increasingly involved in crime, narcotics addiction, and alcoholism, possibly due to a failure of socialization in childhood. Researchers are seeking the origins of this phenomenon and searching for ways to combat it through rehabilitation of juvenile offenders. The essential nature of social and pedagogical…

  14. Multiple Substance Use Disorders in Juvenile Detainees.

    ERIC Educational Resources Information Center

    McClelland, Gary M.; Elkington, Katherine S.; Teplin, Linda A.; Abram, Karen M.

    2004-01-01

    Objective: To estimate the 6-month prevalence of multiple substance use disorders (SUDs) among juvenile detainees by demographic subgroups (sex, race/ethnicity, age). Method: Participants were a randomly selected sample of 1,829 African American, non-Hispanic white, and Hispanic detainees (1,172 males, 657 females, aged 10 to 18). Patterns and…

  15. Juvenile polyp and colonoscopic polypectomy in childhood.

    PubMed

    Lee, Byung Gee; Shin, Sung Hyun; Lee, Young Ah; Wi, Joo Hee; Lee, Yeoun Joo; Park, Jae Hong

    2012-12-01

    This study aimed to evaluate the clinical features of juvenile polyp and the usefulness of polypectomy with entire colonoscopy in children. We retrospectively reviewed the medical records of 83 children who were diagnosed with having juvenile polyps. The mean age of the patients was 6.5±3.7 (range 1.3-14.5 years) years. The male to female ratio was 2.1: 1. Eighty one patients (97.6%) had hematochezia, of which the observed characteristics included red stool (74.1%), blood on wipe (13.6%). The time interval between the 1st episode of hematochezia and colonoscopy was 8.9±20.4 (ranged 0.1-48.0) months. The most proximal regions of colonoscopic approach were terminal ileum (96.4%). Sixty three patients (75.9%) had a solitary polyp and 20 patients (24.1%) had multiple polyps. The sites of the polyps were rectum (61.4%), sigmoid colon (23.5%). Eighteen polyps (15.1%) were found more proximal locations than rectosigmoid. The polyp size ranged from 0.3 to 5 cm. After the polypectomy, hematochezia recurred in 9 patients. Endoscopic hemostasis was performed in 2 patients due to severe bleeding. All procedures were carried out without using general anesthesia. Juvenile polyp occurred in a wide range locations and had variable sizes and numbers, suggesting that colonoscopy on the entire colon is necessary. Colonoscopic polypectomy is a simple and useful therapeutic method in children with juvenile polyp.

  16. Identifying and classifying juvenile stalking behavior.

    PubMed

    Evans, Thomas M; Reid Meloy, J

    2011-01-01

    Despite the growing research in the area of stalking, the focus has been on adults who engage in this behavior. Unfortunately, almost no studies investigate the prevalence of this behavior in adolescents. Two cases are presented demonstrating not only that stalking occurs during the period of adolescence, but also that there is a significant difference in the motivation underlying this behavior that can be classified similarly to that of adult stalkers. Further, a suggested classification based on these two cases as well as our experience with other juveniles who have exhibited stalking behaviors is proposed. The first case involves a narcissistic youth who also possesses psychopathic traits, while the second involves a lonely, severely socially awkward teen. Juvenile stalking is a societal problem that has not yet garnered the attention it deserves, and all systems that deal with juvenile delinquency (juvenile court, law enforcement, and mental health personnel) as well as the school system must be educated to the prevalence and severity of this yet-to-be-recognized problem.

  17. Retrocalcaneal bursitis in juvenile chronic arthritis.

    PubMed Central

    Goldenstein-Schainberg, C; Homsi, C; Rodrigues Pereira, R M; Cossermelli, W

    1992-01-01

    Retrocalcaneal bursitis has been described in various adult rheumatic diseases and septic bursitis unrelated to previous bursal disease has been reported in children. The case is reported here of a girl with juvenile chronic arthritis who developed non-septic retrocalcaneal bursitis; the diagnosis was suggested by a combination of clinical and radiographic studies and was confirmed by ultrasonography. Images PMID:1444631

  18. Do burn centers provide juvenile firesetter intervention?

    PubMed

    Ahrns-Klas, Karla S; Wahl, Wendy L; Hemmila, Mark R; Wang, Stewart C

    2012-01-01

    Juvenile firesetting activity accounts for a significant number of annual injuries and property damage, yet there is sparse information on intervention in the burn literature. To quantify juvenile firesetting intervention (JFSI) in burn centers, a 23-question survey was sent to all directors listed in the American Burn Association Burn Care Facilities Directory.Sixty-four out of 112 (57%) surveys were returned. This represents responses from 79% of currently verified burn centers. When queried on interventions provided to a juvenile firesetter admitted to their unit, 38% report having their own JFSI program and 38% refer the child to fire services. Two thirds of units without a JFSI program treat pediatric patients. Units that previously had a JFSI program report lack of staffing and funding as most common reasons for program discontinuation. Almost all (95%) stated that a visual tool demonstrating legal, financial, social, future, and career ramifications associated with juvenile firesetting would be beneficial to their unit. Many burn units that treat pediatric patients do not have JFSI and rely on external programs operated by fire services. Existing JFSI programs vary greatly in structure and method of delivery. Burn centers should be involved in JFSI, and most units would benefit from a new video toolkit to assist in providing appropriate JFSI. Study results highlight a need for burn centers to collaborate on evaluating effectiveness of JFSI programs and providing consistent intervention materials based on outcomes research.

  19. Juvenile Drug Courts and Teen Substance Abuse

    ERIC Educational Resources Information Center

    Butts, Jeffrey A., Ed.; Roman, John, Ed.

    2004-01-01

    Juvenile justice officials across the United States are embracing a new method of dealing with adolescent substance abuse. Importing a popular innovation from adult courts, state and local governments have started hundreds of specialized drug courts to provide judicial supervision and coordinate substance abuse treatment for drug-involved…

  20. Behavioral science and the juvenile death penalty.

    PubMed

    Leong, G B; Eth, S

    1989-01-01

    Behavioral science data included in an amicus brief has been introduced into a recent Supreme Court decision (Thompson v. Oklahoma) involving the juvenile death penalty. However, a close examination of the data fails to provide support for either the pro- or antijuvenile death penalty position.

  1. Juvenile Court Commitment Rates: The National Picture.

    ERIC Educational Resources Information Center

    Sosin, Michael

    There is less geographic variation in the commitment rate of juvenile offenders than is commonly assumed. Apparently, judges across the country develop a similar standard of what percentage of youths they face should be committed. This standard may be similar across the country because it represents broadly shared ideals. However, there is much…

  2. Youth for Justice. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Nessel, Paula A.

    Youth for Justice uses the power of active learning to teach youth practical information about the law while addressing the risks associated with being young in the United States today. This unique initiative is a law-related education (LRE) program supported by the United States Department of Justice's Office of Juvenile Justice and Delinquency…

  3. Metamorphosis: How Missouri Rehabilitates Juvenile Offenders

    ERIC Educational Resources Information Center

    Dubin, Jennifer

    2012-01-01

    Juveniles convicted of serious offenses usually end up in large correctional facilities that focus on punishment--not rehabilitation. The state of Missouri, however, has found a better way to help end the cycle of crime: by creating a network of small facilities that provide therapy and educational opportunities, it has dramatically reduced…

  4. Juvenile Delinquency. Selected Studies in Social Problems.

    ERIC Educational Resources Information Center

    Korn, Richard R., Ed.

    Excerpts from eight books present material on juvenile delinquency. Included are selections from the following: "Wayward Youth" by August Aichhorn, "The Gang" by Frederic M. Thrasher, "The Jack-Roller" by Clifford R. Shaw, "Street Corner Society" by William Foote Whyte, "Children Who Hate" by Fritz Redl and David Wineman, "The Addict in the…

  5. Successful euthanasia of a juvenile fin whale.

    PubMed Central

    Daoust, P Y; Ortenburger, A I

    2001-01-01

    A stranded juvenile fin whale was successfully euthanized with an intravenous injection of sedative and cardioplegic drugs. Veterinarians may face a number of serious difficulties if called to perform this task, and advance preparation is required for successful euthanasia of these animals. Images Figure 1. PMID:11272456

  6. Attachment Theory Applied to Juvenile Sex Offending.

    ERIC Educational Resources Information Center

    Goodrow, Kenneth K.; Lim, Mee-Gaik

    1998-01-01

    Attachment theory is applied to identify systemic patterns encouraging juveniles to commit sexual offenses. The role of the helping system in perpetuating offenses is reviewed. The priority of family integrity and the role of professionals in breaking cycles of abuse and repairing earlier destructive emotional attachments are discussed. (EMK)

  7. Phototaxis of larval and juvenile northern pike

    USGS Publications Warehouse

    Zigler, S.J.; Dewey, M.R.

    1995-01-01

    Age- Phi northern pike Esox lucius prefer vegetated habitats that are difficult to sample with standard towed gears. Light traps can be effective for sampling larval fishes in dense vegetation, given positive phototaxis of fish. We evaluated the phototactic response of young northern pike by comparing the catches of larvae and juveniles obtained with plexiglass traps deployed with a chemical light stick versus traps deployed without a light source (controls) in a laboratory raceway and in a vegetated pond. In the laboratory tests, catches of protolarvae and mesolarvae in lighted traps were 11-35 times greater than catches in control traps. The catches of juvenile northern pike in field and laboratory experiments were 3-15 times greater in lighted traps than in control traps, even though the maximum body width of the larger juveniles was similar to the width of the entrance slots of the traps (5 mm). Larval and juvenile northern pike were photopositive; thus, light traps should effectively sample age-0 northern pike for at least 6 weeks after hatching.

  8. Family Disruption and Delinquency. Juvenile Justice Bulletin.

    ERIC Educational Resources Information Center

    Thornberry, Terence P.; Smith, Carolyn A.; Rivera, Craig; Huizinga, David; Stouthamer-Loeber, Magda

    At study sites in Rochester (New York), Denver (Colorado) and Pittsburgh (Pennsylvania), three research teams studying the impact of family disruption on juvenile delinquency have interviewed approximately 4,000 participants at regular intervals for a decade, recording their lives in detail. Findings to date indicate that preventing delinquency…

  9. Rehabilitation of the Personality of Juvenile Offenders

    ERIC Educational Resources Information Center

    Zaitsev, G. K.; Zaitsev, A. G.; Dmitriev, M. G.; Apal'kova, I. Iu.

    2009-01-01

    Russian youth has in recent years been increasingly involved in crime, narcotics addiction, and alcoholism, possibly due to a failure of socialization in childhood. Researchers are seeking the origins of this phenomenon and searching for ways to combat it through rehabilitation of juvenile offenders. The essential nature of social and pedagogical…

  10. Juvenile Delinquency and Victimization: A Theoretical Typology

    ERIC Educational Resources Information Center

    Cuevas, Carlos A.; Finkelhor, David; Turner, Heather A.; Ormrod, Richard K.

    2007-01-01

    It is a widely voiced notion that juvenile delinquency and victimization co-occur extensively in the youth population, in particular because delinquent youth engage in risky activities. But theory from the bullying and traumatic stress literatures suggests that there may be additional pathways by which delinquency and victimization are connected.…

  11. Evaluation of a Comprehensive Juvenile Delinquency Program.

    ERIC Educational Resources Information Center

    Young, Howard; And Others

    This paper discribes a comprehensive juvenile delinquency diversion program serving a poverty community in a large urban center, and attempts to evaluate the problems and effects of the program. The target population was primarily minority-group truants, aged 10-15, who had been in trouble with the authorities. The program included recreational…

  12. Multiple Substance Use Disorders in Juvenile Detainees.

    ERIC Educational Resources Information Center

    McClelland, Gary M.; Elkington, Katherine S.; Teplin, Linda A.; Abram, Karen M.

    2004-01-01

    Objective: To estimate the 6-month prevalence of multiple substance use disorders (SUDs) among juvenile detainees by demographic subgroups (sex, race/ethnicity, age). Method: Participants were a randomly selected sample of 1,829 African American, non-Hispanic white, and Hispanic detainees (1,172 males, 657 females, aged 10 to 18). Patterns and…

  13. Juvenile Drug Courts and Teen Substance Abuse

    ERIC Educational Resources Information Center

    Butts, Jeffrey A., Ed.; Roman, John, Ed.

    2004-01-01

    Juvenile justice officials across the United States are embracing a new method of dealing with adolescent substance abuse. Importing a popular innovation from adult courts, state and local governments have started hundreds of specialized drug courts to provide judicial supervision and coordinate substance abuse treatment for drug-involved…

  14. Juvenile Delinquency. Selected Studies in Social Problems.

    ERIC Educational Resources Information Center

    Korn, Richard R., Ed.

    Excerpts from eight books present material on juvenile delinquency. Included are selections from the following: "Wayward Youth" by August Aichhorn, "The Gang" by Frederic M. Thrasher, "The Jack-Roller" by Clifford R. Shaw, "Street Corner Society" by William Foote Whyte, "Children Who Hate" by Fritz Redl and David Wineman, "The Addict in the…

  15. Juvenile Firesetter and School Arson Prevention Programs.

    ERIC Educational Resources Information Center

    Karchmer, Clifford L.

    Designed to provide background information and assistance to educators developing arson prevention programs in the schools, this report reviews existing programs and recent research on juvenile firesetting. Following an introduction, information is divided into four sections. Section 1 emphasizes curiosity and emotional disturbances as underlying…

  16. Predictors of Juvenile Delinquency and Violence.

    ERIC Educational Resources Information Center

    Daley, Christine E.; Onwuegbuzie, Anthony J.

    Violence among youth has reached epidemic proportions. Every five minutes a child is arrested for a violent crime. To understand this trend, this paper examines characteristics of adolescent males who come into contact with the juvenile justice system. The study focuses on drug and alcohol involvement, the relevance of education, sexual practices,…

  17. The Juvenile Justice System. Chapter 6.

    ERIC Educational Resources Information Center

    1996

    This collection of papers presented at a 1996 conference on children's mental health focuses on the juvenile justice system. Papers have the following titles and authors: (1) "Delinquency and Mental Illness: The Intersection of Problems and Systems" (Carolyn S. Breda); (2) "Assessing the Mental Health of Adolescents in the Mental Health and…

  18. Language and Communication Difficulties in Juvenile Offenders

    ERIC Educational Resources Information Center

    Bryan, Karen; Freer, Jackie; Furlong, Cheryl

    2007-01-01

    Background: Studies of the prison population suggest that the numbers of prisoners with language and communication disorders is higher than that of the overall population. However, the prison population is heterogeneous and it is important to focus on specific areas of the population. This study focuses on juvenile offenders. Aims: The study aimed…

  19. Predictors of juveniles' noncompliance with probation requirements.

    PubMed

    NeMoyer, Amanda; Goldstein, Naomi E S; McKitten, Rhonda L; Prelic, Ana; Ebbecke, Jenna; Foster, Erika; Burkard, Casey

    2014-12-01

    Probation is the most common disposition for adjudicated youth, but little is known about which specific requirements are commonly imposed on juveniles, the requirements with which juveniles most often fail to comply, and how certain youth characteristics and/or imposed requirements might relate to probation noncompliance. An investigation of 120 archived files of youth represented by an urban public defender's office identified 29 probation requirements imposed on youth and 18 requirements with which youth commonly failed to comply. Results revealed that 52% of youth failed to comply with at least one probation requirement; prior probation noncompliance and race were both significantly associated with noncompliance in the examined probation disposition. In addition, the probability of probation noncompliance was significantly higher when youth received either of two substance-related probation requirements: drug tests or drug and alcohol counseling. Such results may prompt further investigation of juvenile probation-related predictors, identify areas of need for clinical service provision to foster successful completion of probation requirements, and help identify areas of potential biases among juvenile court personnel. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  20. Evaluating Juvenile Detainees' Miranda Misconceptions: The Discriminant Validity of the Juvenile Miranda Quiz.

    PubMed

    Sharf, Allyson J; Rogers, Richard; Williams, Margot M; Drogin, Eric Y

    2016-08-08

    Most juvenile arrestees in custodial settings waive their Miranda rights almost immediately, and many then provide incriminating statements, if not outright confessions. Forensic practitioners are then asked to provide retrospective determinations regarding whether these waivers were effectuated knowingly, voluntarily, and intelligently. At present, the forensic assessment instrument for juvenile Miranda issues consists of the Miranda Rights Comprehension Instruments (MRCI)-which as its name implies-focuses mostly on Miranda comprehension with a de-emphasis of Miranda reasoning. In partially addressing this gap, the current study investigated the clinical utility of the Juvenile Miranda Quiz (JMQ) for evaluating key Miranda misconceptions, a critically important component of Miranda reasoning. Using data from 201 juvenile detainees, we evaluated the JMQ's discriminability with regards to cognitive variables and MRCI scales. Many moderate effect sizes in the predicted direction were found for the JMQ Primary Total and Juvenile Total scores. Finally, these detainees were tested using a mock crime scenario with a representative Miranda warning plus a brief interrogation to evaluate whether they would waive their rights, and if so, whether they would confess. Using Miranda measures to predict problematic outcomes (i.e., impaired waivers followed by confessions), the JMQ Juvenile Total proved the most successful. These findings are discussed within the context of the "intelligent" prong of Miranda waivers. (PsycINFO Database Record

  1. Risk-taking behavior in juvenile myoclonic epilepsy

    PubMed Central

    Wandschneider, Britta; Centeno, Maria; Vollmar, Christian; Stretton, Jason; O’Muircheartaigh, Jonathan; Thompson, Pamela J; Kumari, Veena; Symms, Mark; Barker, Gareth J; Duncan, John S; Richardson, Mark P; Koepp, Matthias J

    2013-01-01

    Objective Patients with juvenile myoclonic epilepsy (JME) often present with risk-taking behavior, suggestive of frontal lobe dysfunction. Recent studies confirm functional and microstructural changes within the frontal lobes in JME. This study aimed at characterizing decision-making behavior in JME and its neuronal correlates using functional magnetic resonance imaging (fMRI). Methods We investigated impulsivity in 21 JME patients and 11 controls using the Iowa Gambling Task (IGT), which measures decision making under ambiguity. Performance on the IGT was correlated with activation patterns during an fMRI working memory task. Results Both patients and controls learned throughout the task. Post hoc analysis revealed a greater proportion of patients with seizures than seizure-free patients having difficulties in advantageous decision making, but no difference in performance between seizure-free patients and controls. Functional imaging of working memory networks showed that overall poor IGT performance was associated with an increased activation in the dorsolateral prefrontal cortex (DLPFC) in JME patients. Impaired learning during the task and ongoing seizures were associated with bilateral medial prefrontal cortex (PFC) and presupplementary motor area, right superior frontal gyrus, and left DLPFC activation. Significance Our study provides evidence that patients with JME and ongoing seizures learn significantly less from previous experience. Interictal dysfunction within “normal” working memory networks, specifically, within the DLPFC and medial PFC structures, may affect their ability to learn. PMID:24138327

  2. Old Dogs Learning New Tricks: Neuroplasticity Beyond the Juvenile Period

    PubMed Central

    Lillard, Angeline S.; Erisir, Alev

    2014-01-01

    Twenty years ago, the prevalent view in psychology was that although learning and the formation of new memories are lifelong occurrences, the neural changes associated with these events were all in the existing receptors. No new neural hardware, from synapses to neurons, was thought to appear after a protracted period early in life. In the past 20 years, another view has supplanted this one, showing that although the juvenile period is especially suited to neuroplastic adaptation, there is hard neuroplastic change later in life as well. We review a selection of evidence for this view from both animal and human models, showing how it reflects three principles of neuroplasticity: 1) earlier and later experience-induced changes to neuroarchitecture differ in degree more so than in type; 2) the types of experiences that lead to neuroplastic change narrow with age; and 3) differences in the amenability of neural circuitry to change result from basic differences in neuroarchitecture and neuroenvironment in different phases of development. PMID:24648605

  3. Musculoskeletal MRI findings of juvenile localized scleroderma.

    PubMed

    Eutsler, Eric P; Horton, Daniel B; Epelman, Monica; Finkel, Terri; Averill, Lauren W

    2017-04-01

    Juvenile localized scleroderma comprises a group of autoimmune conditions often characterized clinically by an area of skin hardening. In addition to superficial changes in the skin and subcutaneous tissues, juvenile localized scleroderma may involve the deep soft tissues, bones and joints, possibly resulting in functional impairment and pain in addition to cosmetic changes. There is literature documenting the spectrum of findings for deep involvement of localized scleroderma (fascia, muscles, tendons, bones and joints) in adults, but there is limited literature for the condition in children. We aimed to document the spectrum of musculoskeletal magnetic resonance imaging (MRI) findings of both superficial and deep juvenile localized scleroderma involvement in children and to evaluate the utility of various MRI sequences for detecting those findings. Two radiologists retrospectively evaluated 20 MRI studies of the extremities in 14 children with juvenile localized scleroderma. Each imaging sequence was also given a subjective score of 0 (not useful), 1 (somewhat useful) or 2 (most useful for detecting the findings). Deep tissue involvement was detected in 65% of the imaged extremities. Fascial thickening and enhancement were seen in 50% of imaged extremities. Axial T1, axial T1 fat-suppressed (FS) contrast-enhanced and axial fluid-sensitive sequences were rated most useful. Fascial thickening and enhancement were the most commonly encountered deep tissue findings in extremity MRIs of children with juvenile localized scleroderma. Because abnormalities of the skin, subcutaneous tissues and fascia tend to run longitudinally in an affected limb, axial T1, axial fluid-sensitive and axial T1-FS contrast-enhanced sequences should be included in the imaging protocol.

  4. Pacemaking Kisspeptin Neurons

    PubMed Central

    Kelly, Martin J.; Zhang, Chunguang; Qiu, Jian; Rønnekleiv, Oline K.

    2013-01-01

    Kisspeptin (Kiss1) neurons are vital for reproduction. GnRH neurons express the kisspeptin receptor, GPR 54, and kisspeptins potently stimulate the release of GnRH by depolarising and inducing sustained action potential firing in GnRH neurons. As such Kiss1 neurons may be the pre-synaptic pacemaker neurons in the hypothalamic circuitry that controls reproduction. There are at least two different populations of Kiss1 neurons: one in the rostral periventricular area (RP3V) that is stimulated by oestrogens and the other in the arcuate nucleus that is inhibited by oestrogens. How each of these Kiss1 neuronal populations participate in the regulation of the reproductive cycle is currently under intense investigation. Based on electrophysiological studies in the guinea pig and mouse, Kiss1 neurons in general are capable of generating burst firing behavior. Essentially all Kiss1 neurons, which have been studied thus far in the arcuate nucleus, express the ion channels necessary for burst firing, which include hyperpolarization-activated, cyclic nucleotide gated cation (HCN) channels and the T-type calcium (Cav3.1) channels. Under voltage clamp conditions, these channels produce distinct currents that under current clamp conditions can generate burst firing behavior. The future challenge is to identify other key channels and synaptic inputs involved in the regulation of the firing properties of Kiss1 neurons and the physiological regulation of the expression of these channels and receptors by oestrogens and other hormones. The ultimate goal is to understand how Kiss1 neurons control the different phases of GnRH neurosecretion and hence reproduction. PMID:23884368

  5. The transmembrane topology of Batten disease protein CLN3 determined by consensus computational prediction constrained by experimental data.

    PubMed

    Nugent, Timothy; Mole, Sara E; Jones, David T

    2008-04-02

    The CLN3 gene encodes an integral membrane protein of unknown function. Mutations in CLN3 can cause juvenile neuronal ceroid lipofuscinosis, or Batten disease, an inherited neurodegenerative lysosomal storage disease affecting children. Here, we report a topological study of the CLN3 protein using bioinformatic approaches constrained by experimental data. Our results suggest that CLN3 has a six transmembrane helix topology with cytoplasmic N and C-termini, three large lumenal loops, one of which may contain an amphipathic helix, and one large cytoplasmic loop. Surprisingly, varied topological predictions were made using different subsets of orthologous sequences, highlighting the challenges still remaining for bioinformatics.

  6. Batten disease: past, present, and future.

    PubMed

    Rider, J A; Rider, D L

    1988-01-01

    The name Batten disease (or neuronal ceroid lipofuscinosis) is used to unify the spectrum of clinical and pathological conditions covered by the names infantile, late infantile, juvenile, and adult variants with their respective eponyms. The past was largely devoted to clinical diagnosis. The present is devoted to specific diagnostic tests. The future will be devoted to prevention and treatment. Treatment may consist of specific drug treatment, enzyme replacement, or gene replacement. Early diagnosis is important in order to provide genetic counseling and to establish family support for those patients who have a protracted, progressive disabling and ultimate fatal course.

  7. Neuronal Mechanisms of Intelligence.

    DTIC Science & Technology

    1986-03-21

    The underlying premise of this research is that the neuron itself is the functional unit in the brain for positive reinforcement . Our early studies...preference studies (an alternative method to self-stimulation for measuring reward). Keywords: Neuronal conditioning; Positive reinforcement ; Learning; and Adaptive networks.

  8. Culturing rat hippocampal neurons.

    PubMed

    Audesirk, G; Audesirk, T; Ferguson, C

    2001-01-01

    Cultured neurons are widely used to investigate the mechanisms of neurotoxicity. Embryonic rat hippocampal neurons may be grown as described under a wide variety of conditions to suit differing experimental procedures, including electrophysiology, morphological analysis of neurite development, and various biochemical and molecular analyses.

  9. Corticospinal mirror neurons.

    PubMed

    Kraskov, A; Philipp, R; Waldert, S; Vigneswaran, G; Quallo, M M; Lemon, R N

    2014-01-01

    Here, we report the properties of neurons with mirror-like characteristics that were identified as pyramidal tract neurons (PTNs) and recorded in the ventral premotor cortex (area F5) and primary motor cortex (M1) of three macaque monkeys. We analysed the neurons' discharge while the monkeys performed active grasp of either food or an object, and also while they observed an experimenter carrying out a similar range of grasps. A considerable proportion of tested PTNs showed clear mirror-like properties (52% F5 and 58% M1). Some PTNs exhibited 'classical' mirror neuron properties, increasing activity for both execution and observation, while others decreased their discharge during observation ('suppression mirror-neurons'). These experiments not only demonstrate the existence of PTNs as mirror neurons in M1, but also reveal some interesting differences between M1 and F5 mirror PTNs. Although observation-related changes in the discharge of PTNs must reach the spinal cord and will include some direct projections to motoneurons supplying grasping muscles, there was no EMG activity in these muscles during action observation. We suggest that the mirror neuron system is involved in the withholding of unwanted movement during action observation. Mirror neurons are differentially recruited in the behaviour that switches rapidly between making your own movements and observing those of others.

  10. Peripheral competition in the control of sensory neuron numbers in Xenopus frogs reared with a single bilaterally innervated hindlimb.

    PubMed

    Lamb, A H; Ferns, M J; Klose, K

    1989-01-01

    Sensory neurons were counted in the hind-limb innervating spinal ganglia on both sides of juvenile Xenopus frogs which, as tadpoles, had had one hind limb bud amputated prior to innervation, and a channel made to allow innervation of the remaining limb bud from both sides. The total number of sensory neurons surviving on the two sides approximated the number on one side of normal frogs, the ipsilateral and contralateral numbers being negatively correlated. These effects differ markedly from the effects on motoneuron numbers, suggesting different control mechanisms of cell death in the two neuronal classes.

  11. NEURON and Python.

    PubMed

    Hines, Michael L; Davison, Andrew P; Muller, Eilif

    2009-01-01

    The NEURON simulation program now allows Python to be used, alone or in combination with NEURON's traditional Hoc interpreter. Adding Python to NEURON has the immediate benefit of making available a very extensive suite of analysis tools written for engineering and science. It also catalyzes NEURON software development by offering users a modern programming tool that is recognized for its flexibility and power to create and maintain complex programs. At the same time, nothing is lost because all existing models written in Hoc, including graphical user interface tools, continue to work without change and are also available within the Python context. An example of the benefits of Python availability is the use of the xml module in implementing NEURON's Import3D and CellBuild tools to read MorphML and NeuroML model specifications.

  12. NEURON and Python

    PubMed Central

    Hines, Michael L.; Davison, Andrew P.; Muller, Eilif

    2008-01-01

    The NEURON simulation program now allows Python to be used, alone or in combination with NEURON's traditional Hoc interpreter. Adding Python to NEURON has the immediate benefit of making available a very extensive suite of analysis tools written for engineering and science. It also catalyzes NEURON software development by offering users a modern programming tool that is recognized for its flexibility and power to create and maintain complex programs. At the same time, nothing is lost because all existing models written in Hoc, including graphical user interface tools, continue to work without change and are also available within the Python context. An example of the benefits of Python availability is the use of the xml module in implementing NEURON's Import3D and CellBuild tools to read MorphML and NeuroML model specifications. PMID:19198661

  13. Imaging calcium in neurons.

    PubMed

    Grienberger, Christine; Konnerth, Arthur

    2012-03-08

    Calcium ions generate versatile intracellular signals that control key functions in all types of neurons. Imaging calcium in neurons is particularly important because calcium signals exert their highly specific functions in well-defined cellular subcompartments. In this Primer, we briefly review the general mechanisms of neuronal calcium signaling. We then introduce the calcium imaging devices, including confocal and two-photon microscopy as well as miniaturized devices that are used in freely moving animals. We provide an overview of the classical chemical fluorescent calcium indicators and of the protein-based genetically encoded calcium indicators. Using application examples, we introduce new developments in the field, such as calcium imaging in awake, behaving animals and the use of calcium imaging for mapping single spine sensory inputs in cortical neurons in vivo. We conclude by providing an outlook on the prospects of calcium imaging for the analysis of neuronal signaling and plasticity in various animal models.

  14. Neuronal signaling through endocytosis.

    PubMed

    Cosker, Katharina E; Segal, Rosalind A

    2014-02-01

    The distinctive morphology of neurons, with complex dendritic arbors and extensive axons, presents spatial challenges for intracellular signal transduction. The endosomal system provides mechanisms that enable signaling molecules initiated by extracellular cues to be trafficked throughout the expanse of the neuron, allowing intracellular signals to be sustained over long distances. Therefore endosomes are critical for many aspects of neuronal signaling that regulate cell survival, axonal growth and guidance, dendritic branching, and cell migration. An intriguing characteristic of neuronal signal transduction is that endosomal trafficking enables physiological responses that vary based on the subcellular location of signal initiation. In this review, we will discuss the specialized mechanisms and the functional significance of endosomal signaling in neurons, both during normal development and in disease.

  15. Neuronal Signaling through Endocytosis

    PubMed Central

    Cosker, Katharina E.; Segal, Rosalind A.

    2014-01-01

    The distinctive morphology of neurons, with complex dendritic arbors and extensive axons, presents spatial challenges for intracellular signal transduction. The endosomal system provides mechanisms that enable signaling molecules initiated by extracellular cues to be trafficked throughout the expanse of the neuron, allowing intracellular signals to be sustained over long distances. Therefore endosomes are critical for many aspects of neuronal signaling that regulate cell survival, axonal growth and guidance, dendritic branching, and cell migration. An intriguing characteristic of neuronal signal transduction is that endosomal trafficking enables physiological responses that vary based on the subcellular location of signal initiation. In this review, we will discuss the specialized mechanisms and the functional significance of endosomal signaling in neurons, both during normal development and in disease. PMID:24492712

  16. Nervous system development in lecithotrophic larval and juvenile stages of the annelid Capitella teleta.

    PubMed

    Meyer, Néva P; Carrillo-Baltodano, Allan; Moore, Richard E; Seaver, Elaine C

    2015-01-01

    Reconstructing the evolutionary history of nervous systems requires an understanding of their architecture and development across diverse taxa. The spiralians encompass diverse body plans and organ systems, and within the spiralians, annelids exhibit a variety of morphologies, life histories, feeding modes and associated nervous systems, making them an ideal group for studying evolution of nervous systems. We describe nervous system development in the annelid Capitella teleta (Blake JA, Grassle JP, Eckelbarger KJ. Capitella teleta, a new species designation for the opportunistic and experimental Capitella sp. I, with a review of the literature for confirmed records. Zoosymposia. 2009;2:25-53) using whole-mount in situ hybridization for a synaptotagmin 1 homolog, nuclear stains, and cross-reactive antibodies against acetylated α-tubulin, 5-HT and FMRFamide. Capitella teleta is member of the Sedentaria (Struck TH, Paul C, Hill N, Hartmann S, Hosel C, Kube M, et al. Phylogenomic analyses unravel annelid evolution. Nature. 2011;471:95-8) and has an indirectly-developing, lecithotrophic larva. The nervous system of C. teleta shares many features with other annelids, including a brain and a ladder-like ventral nerve cord with five connectives, reiterated commissures, and pairs of peripheral nerves. Development of the nervous system begins with the first neurons differentiating in the brain, and follows a temporal order from central to peripheral and from anterior to posterior. Similar to other annelids, neurons with serotonin-like-immunoreactivity (5HT-LIR) and FMRFamide-like-immunoreactivity (FMRF-LIR) are found throughout the brain and ventral nerve cord. A small number of larval-specific neurons and neurites are present, but are visible only after the central nervous system begins to form. These larval neurons are not visible after metamorphosis while the rest of the nervous system is largely unchanged in juveniles. Most of the nervous system that forms during

  17. Cajal bodies in neurons

    PubMed Central

    Lafarga, Miguel; Tapia, Olga; Romero, Ana M.; Berciano, Maria T.

    2017-01-01

    ABSTRACT Cajal is commonly regarded as the father of modern neuroscience in recognition of his fundamental work on the structure of the nervous system. But Cajal also made seminal contributions to the knowledge of nuclear structure in the early 1900s, including the discovery of the “accessory body” later renamed “Cajal body” (CB). This important nuclear structure has emerged as a center for the assembly of ribonucleoproteins (RNPs) required for splicing, ribosome biogenesis and telomere maintenance. The modern era of CB research started in the 1990s with the discovery of coilin, now known as a scaffold protein of CBs, and specific probes for small nuclear RNAs (snRNAs). In this review, we summarize what we have learned in the recent decades concerning CBs in post-mitotic neurons, thereby ruling out dynamic changes in CB functions during the cell cycle. We show that CBs are particularly prominent in neurons, where they frequently associate with the nucleolus. Neuronal CBs are transcription-dependent nuclear organelles. Indeed, their number dynamically accommodates to support the high neuronal demand for splicing and ribosome biogenesis required for sustaining metabolic and bioelectrical activity. Mature neurons have canonical CBs enriched in coilin, survival motor neuron protein and snRNPs. Disruption and loss of neuronal CBs associate with severe neuronal dysfunctions in several neurological disorders such as motor neuron diseases. In particular, CB depletion in motor neurons seems to reflect a perturbation of transcription and splicing in spinal muscular atrophy, the most common genetic cause of infant mortality. PMID:27627892

  18. The impact of schools on juvenile substance initiation and use.

    PubMed

    Amuedo-Dorantes, Catalina; Mach, Traci; Clapp, John D

    2004-06-01

    We use data from the two rounds of the NLSY97 and the corresponding QED data to examine the effectiveness of school endowments and curricula in targeting juvenile use of tobacco, alcohol, and marijuana. Our results support the notion that schools matter in reducing juvenile involvement in substance use. Higher discretionary dollars per pupil are linked to reduced rates of juvenile initiation and repetitive use rates of cigarettes and marijuana. Additionally, school curricula, as indicated by the implementation of year round classes and some innovative and after-school programs--such as gifted and talented, attendance monitoring, homework hotline, international baccalaureate, extended-day, and mentoring, programs, affect both juvenile initiation to tobacco and alcohol use and juvenile repetitive use of tobacco and alcohol. In particular, we find that juvenile initiation to cigarette use is approximately between 2 percentage points and 3 percentage points lower among youths attending schools with gifted and talented and international baccalaureate programs. In addition, juvenile repetitive cigarette use is approximately 54%, 52%, and 48% lower among youths attending schools offering year round classes, international baccalaureate, and twenty-first century programs, respectively. Finally, juvenile initiation to alcohol use and juvenile repetitive use of alcohol are approximately 3% and 20% lower, respectively, among youths in schools offering gifted and talented programs. In sum, while these programs are not implemented to address substance use problems among the student body, we find that the implementation of these programs is often accompanied by a reduction in juvenile initiation and repetitive substance use.

  19. Movements of juvenile common ravens in an arid landscape

    USGS Publications Warehouse

    Webb, W.C.; Boarman, W.I.; Rotenberry, J.T.

    2009-01-01

    Movement patterns of juvenile birds are poorly understood, yet critically important ecological phenomena, especially for species with a prolonged juvenile period. We evaluated postfledging movements of juvenile common ravens (Corvus corax) in a western Mojave Desert landscape composed of a mosaic of natural and anthropogenic elements. Generally, ravens do not begin breeding until after their fourth year. We marked 2 annual cohorts of juvenile ravens and followed them from dispersal from their natal territory for up to 33 months. Movements of juvenile common ravens were similar for males and females. Conspecifics and confined livestock feeding operations represented important resources for juvenile ravens, and juveniles were rarely located in open desert. However, initial movements from the natal territory to the nearest communal point subsidy rather than the closest anthropogenic resource suggested juvenile dispersal was influenced by the combination of conspecifics and anthropogenic resources, rather than the distribution of those resources. Land managers concerned with growing raven populations should reduce access to concentrated anthropogenic resources such as landfills and dairies, which serve as important resources for juveniles. Because juvenile ravens rarely venture into open desert, reducing their numbers by lethal removal or other means is unlikely to lessen raven predation of desert tortoises (Gopherus agassizii).

  20. Social experience induces sex-specific fos expression in the amygdala of the juvenile rat.

    PubMed

    Weathington, Jill M; Strahan, J Alex; Cooke, Bradley M

    2012-07-01

    To compare the response of the medial amygdala and central amygdala to juvenile social subjugation (JSS), we used unbiased stereology to quantify the immediate early gene product Fos in prepubertal rats after aggressive or benign social encounters or handling. We estimated the overall number of neurons and the proportion of Fos immunoreactive neurons in the posterodorsal (MePD) and posteroventral medial amygdala (MePV) and the central amygdala (CeA). Experience elicited Fos in a sex- and hemisphere-dependent manner in the MePD. The left MePD was selective for JSS in both sexes, but the right MePD showed a specific Fos response to JSS in males only. In the MePV, irrespective of hemisphere or sex, JSS elicited the greatest amount of Fos, benign social experience elicited an intermediate level, and handling the least. None of the experiential conditions elicited significant levels of Fos in the CeA. We found a previously unreported sex difference in the number of CeA neurons (M>F) that was highly significant and a strong trend toward a sex difference (M>F) in the MePD. These data show that the posterior MeA subnuclei are more responsive to JSS than to benign social interaction, that sex interacts with hemispheric laterality to determine the response of the MePD to JSS and that the MePV responds to social experience and JSS. Taken together, these findings support the hypothesis that juvenile rats process JSS in a sex-specific manner.