bluuebunny/crossref_metadata_2025_split huggingface dataset:
Muscarinic m1 and m2 receptor proteins in local circuit and projection neurons of the primate striatum: Anatomical evidence for cholinergic modulation of glutamatergic prefronto‐striatal pathways
Authors: Alcantara Adriana A. , Mrzljak Ladislav , Jakab Robert L. , Levey Allan I. , Hersch Steven M. , Goldman‐Rakic Patricia S. 
Published: August 2002

AbstractThe cellular and subcellular localization of muscarinic receptor proteins m1 and m2 was examined in the neostriatum of macaque monkeys by using light and electron microscopic immunocytochemical techniques. Double‐labeling immunocytochemistry revealed m1 receptors in calbindin‐D28k–positive medium spiny projection neurons. Muscarinic m1 labeling was dramatically more intense in the striatal matrix compartment in juvenile monkeys but more intense in striosomes in the adult caudate, suggesting that m1 expression undergoes a developmental age‐dependent change. Ultrastructurally, m1 receptors were predominantly localized in asymmetric synapse‐forming spines, indicating that these spines receive extrastriatal excitatory afferents. The association of m1‐positive spines with lesion‐induced degenerating prefronto‐striatal axon terminals demonstrated that these afferents originate in part from the prefrontal cortex. The synaptic localization of m1 in these spines indicates a role of m1 in the modulation of excitatory neurotransmission. To a lesser extent, m1 was present in symmetric synapses, where it may also modulate inhibitory neurotransmission originating from local striatal neurons or the substantia nigra. Conversely, m2/choline acetyltransferase (ChAT) double labeling revealed that m2‐positive neurons corresponded to large aspiny cholinergic interneurons and ultrastructurally, that the majority of m2 labeled axons formed symmetric synapses. The remarkable segregation of the m1 and m2 receptor proteins to projection and local circuit neurons suggests a functional segregation of m1 and m2 mediated cholinergic actions in the striatum: m1 receptors modulate extrinsic glutamatergic and monoaminergic afferents and intrinsic GABAergic afferents onto projection neurons, whereas m2 receptors regulate acetylcholine release from axons of cholinergic interneurons. J. Comp. Neurol. 434:445–460, 2001. © 2001 Wiley‐Liss, Inc.
Connexin43 null mutation increases infarct size after stroke
Authors: Siushansian Ramin , Bechberger John F. , Cechetto David F. , Hachinski Vladimir C. , Naus Christian C.G. 
Published: August 2002

AbstractGlial‐neuronal interactions have been implicated in both normal information processing and neuroprotection. One pathway of cellular interactions involves gap junctional intercellular communication (GJIC). In astrocytes, gap junctions are composed primarily of the channel protein connexin43 (Cx43) and provide a substrate for formation of a functional syncytium implicated in the spatial buffering capacity of astrocytes. To study the function of gap junctions in the brain, we used heterozygous Cx43 null mice, which exhibit reduced Cx43 expression. Western blot analysis showed a reduction in the level of Cx43 protein and GJIC in astrocytes cultured from heterozygote mice. The level of Cx43 is reduced in the adult heterozygote cerebrum to 40% of that present in the wild‐type. To assess the effect of reduced Cx43 and GJIC on neuroprotection, we examined brain infarct volume in wild‐type and heterozygote mice after focal ischemia. In our model of focal stroke, the middle cerebral artery was occluded at two points, above and below the rhinal fissure. Four days after surgery, mice were killed, the brains were sectioned and analyzed. Cx43 heterozygous null mice exhibited a significantly larger infarct volume compared with wild‐type (14.4 ± 1.4 mm3 vs. 7.7 ± 0.82 mm3, P < 0.002). These results suggest that augmentation of GJIC in astrocytes may contribute to neuroprotection after ischemic injury. J. Comp. Neurol. 440:387–394, 2001. © 2001 Wiley‐Liss, Inc.
Treatment of attention‐deficit hyperactivity disorder: the impact of comorbidity
Authors: Pelham William E. , Fabiano Gregory A. 
Published: August 2002

AbstractA significant percentage of children with attention‐deficit hyperactivity disorder (ADHD) have comorbid, associated problems, such as learning disabilities, oppositional defiant disorder, conduct disorder, and internalizing disorders. However, it will be argued that comorbid diagnoses are not useful in treatment planning. In order to effectively treat the problematic behaviours associated with these comorbidities, clinicians must systematically assess for the impairment related to these comorbidities and implement treatment aimed to reduce impaired functioning and increase competencies in important functional domains. Clinicians who utilize this approach will find (1) that diagnosis matters little for treatment planning, while functional impairment matters a great deal, and (2) that the systematic application of behaviour modification principles improves functioning across diagnostic categories. A case study of a multiply comorbid child with ADHD is presented to illustrate effective treatment for ADHD and comorbid disorders. Copyright © 2001 John Wiley & Sons, Ltd.
School refusal: categorical diagnoses, functional analysis and treatment planning
Authors: King Neville J. , Heyne David , Tonge Bruce , Gullone Eleonora , Ollendick Thomas H. 
Published: August 2002

AbstractSchool refusal is a complex and challenging problem for school personnel and mental health professionals. However, school refusal behaviour can be successfully treated provided there has been a sound assessment. We outline an hypothesis‐testing, multi‐informant assessment approach that incorporates diagnostic interviewing, functional analysis assessment, self‐report measures, parent/teacher checklists and review of school attendance records. Further, it is shown how assessment information facilitates individual treatment planning for the school‐refusing child and family. We also discuss the issue of graduated versus rapid school return arrangements. Copyright © 2001 John Wiley & Sons, Ltd.
Automated identification of diploid reference cells in cervical smears using image analysis
Authors: van der Laak Jeroen A.W.M. , Siebers Albertus G. , Cuijpers Vincent M.J.I. , Pahlplatz Martin M.M. , de Wilde Peter C.M. , Hanselaar Antonius G.J.M. 
Published: August 2002

AbstractBackgroundAcquisition of DNA ploidy histograms by image analysis may yield important information regarding the behavior of premalignant cervical lesions. Accurate selection of nuclei for DNA measurement is an important prerequisite for obtaining reliable data. Traditionally, manual selection of nuclei of diagnostic and reference cells is performed by an experienced cytotechnologist. In the present study, a method for the fully automated identification of nuclei of diploid epithelial reference cells in Feulgen‐ restained Papanicolaou (PAP) smears is described.MethodsThe automated procedure consists of a decision tree implemented on the measurement device, containing nodes with feature threshold values and multivariate discriminant functions. Nodes were constructed to recognize debris and inflammatory cells, as well as diploid and nondiploid epithelial cells of the uterine cervix. Evaluation of the classifier was performed by comparing resulting diploid integrated optical densities with those from manually selected reference cells.Results and ConclusionOn average, automatically acquired values deviated 2.4% from manually acquired values, indicating that the method described in this paper may be useful in cytometric practice. Cytometry 47:256–264, 2002. © 2002 Wiley‐Liss, Inc.
Evaluation of stabilized blood cell products as candidate preparations for quality assessment programs for CD4 T‐cell counting
Authors: Bergeron Michèle , Shafaie Atousa , Ding Tao , Phaneuf Sieglinde , Soucy Nadia , Mandy Francis , Bradley John , Fahey John 
Published: August 2002

AbstractBACKGROUNDExceptionally robust cell preparations are needed for quality assessment programs (QAPs) such as the International Program for Quality Assessment and Standardization for Immunological Measures (QASI) relevant to HIV/AIDS. A suitable product must withstand environmental stress related to transportation for a minimum of 6 days. The two objectives of this study are (1) to evaluate the performance of various commercial preparations with multicenter participation and (2) to evaluate the robustness of stabilized blood cell products. Methods: Phase 1: The performance of stabilized blood cell products was evaluated in a multicenter QAP utilizing various staining procedures and flow cytometers. Absolute cell enumeration was achieved using single‐platform T‐cell subset methodology. Phase 2: The robustness of stabilized blood cell products was evaluated by monitoring T‐cell subset values from samples stored at 4°C, 22°C, and 37°C for up to 10 days. Results: The largest interlaboratory variation in both absolute and relative T‐cell values was 16% in samples with CD4 levels ≥400 cells per microliter and 21% in samples with CD4 levels <400 cells per microliter. Six preparations retained their phenotypic expression for 7 days at 4°C and 22°C. However, only two preparations remained stable for 4 days at 37°C. Conclusion: Some stabilized cell preparations are more robust and therefore more suitable for quality assessment purposes. Cytometry (Clin. Cytometry) 50:86–91, 2002. © 2002 Wiley‐Liss, Inc.
Multiparameter flow cytometric approach for simultaneous evaluation of T lymphocyte‐endothelial cell interactions
Authors: Krupnick Alexander S. , Kreisel Daniel , Szeto Wilson Y. , Popma Sicco H. , Amin Kunjlata M. , Moore Jonni S. , Rosengard Bruce R. 
Published: August 2002

AbstractSince vascular endothelium is now recognized as an immunologically active tissue, a better understanding of the relationship between endothelial cells and T lymphocytes is critical to the field of solid organ transplantation. Investigations of endothelial cell‐T cell interactions have been limited by methodology. We developed a flow cytometric method allowing for concurrent investigation of multiple cell populations within the same culture that can be applied to these complex interactions. Allogeneic CD8+ or CD4+ T cells labeled with 5,6‐carboxyfluorescein diacetate succinimidyl ester (CFSE) were added to a murine endothelial cell monolayer, in which endothelial proliferation was not inhibited by irradiation or addition of a cell cycle‐blocking agent. At specific time points, the coculture was analyzed by flow cytometry. T‐cell proliferation could be detected by gating on the T‐cell subset and evaluating the CFSE fluorescence peaks. By directly analyzing cellular division, we minimized erroneous interpretation of the data encountered by previous studies, which utilized 3H‐thymidine incorporation as sole measure of proliferation. Further subgating on cells that divided facilitated the study of CD8+ lymphocyte activation, differentiation, and acquisition of effector function. By gating on the endothelial cell population, phenotypic changes such as upregulation of surface MHC molecules or immune‐mediated apoptosis could be detected. In conclusion, we present a flow cytometric approach that could have important applications for clinical immunological monitoring in allogeneic or xenogeneic transplantation, and might provide the requisite information to better tailor immunotherapy to prevent chronic rejection. Cytometry (Comm. Clin. Cytometry) 46:271–280, 2001. © 2001 Wiley‐Liss, Inc.
Doublet discrimination in DNA cell‐cycle analysis
Authors: Wersto Robert P. , Chrest Francis J. , Leary James F. , Morris Christa , Stetler‐Stevenson MaryAlice , Gabrielson Edward 
Published: August 2002

AbstractDifferences in doublet analysis have the potential to alter DNA cell‐cycle measurements. The techniques for doublet determination are often used interchangeably without regard for the complexity in cell shapes and sizes of biological specimens.G0/1 doublets were identified and quantitated using fluorescence height versus area and fluorescence width versus area pulse measurements, by enumerating the proportion of G2 + M cells that lack cyclin B1 immunoreactivity, and modeled in the DNA histograms by software algorithms. These techniques were tested on propidium iodide‐stained whole epithelial cells or nuclei from asynchronous cultures, or after exposure to chemotherapeutic agents that induced cell‐cycle arrest and were extended to human breast tumor specimens having DNA diploid patterns.G0/1 doublets were easily discernible from G2 + M singlets in cells or nuclei that are generally homogenous and spherical in shape. Doublet discrimination based on pulse processing or cyclin B1 measurements was nonconcordant in some nonspherical cell types and in cells following cell cycle arrest. Significant differences in G0/1 doublet estimates were observed in breast tumor specimens (n = 50), with estimates based on pulse width twice those of pulse height and nearly five times greater than computer estimates. Differences between techniques are attributed to difficulties in the separation of the boundaries between G0/1 doublets and G2 + M singlet populations in biologically heterogeneous specimens.To improve reproducibility and enhance standardization among laboratories performing cell cycle analysis in experimental cell systems and in human breast tumors, doublet discrimination analysis should best be accomplished by computer modeling. Shape and size heterogeneity of tumor and arrested cells using pulse‐processing can lead to errors and make interlaboratory comparison difficult. Cytometry (Comm. Clin. Cytometry) 46:296–306, 2001. Published 2001 Wiley‐Liss, Inc.
Dual actions of A2A adenosine receptor antagonists on motor dysfunction and neurodegenerative processes
Authors: Ongini Ennio , Monopoli Angela , Impagnatiello Francesco , Fredduzzi Silva , Schwarzschild Michael , Chen Jiang‐Fan 
Published: August 2002

AbstractOf the four known adenosine receptors, the A2A receptor has received much attention over the last few years. The discovery of high‐affinity and selective A2A adenosine receptor antagonists, together with the development of different genetic lines of mice lacking A2A receptors, have greatly contributed to the new insights into the mechanisms whereby A2A receptors modulate central nervous system functions. Efforts made using the prototypic A2A receptor antagonists, e.g., the 8‐styrylxanthine KW 6002 and the pyrazolotriazolopyrimidine SCH 58261, have shown that these drugs are effective in different models of motor impairment mimicking the main features of Parkinson’s disease. Moreover, these drugs show neuroprotective properties in models of brain injury. Consistent with pharmacology, A2A receptor knockout mice have been found to be less sensitive to both motor impairment and neurochemical changes relevant to neurodegenerative disorders. The main effect of A2A receptor blockade or inactivation is related to selective interaction with dopamine‐mediated function in the striatum. However, there are responses which appear to be independent of dopamine receptors while the mechanisms underlying neuroprotection remain to be elucidated. Overall, there are now compounds that appear to be promising for treatment of Parkinson’s disease and related neurodegenerative disorders. The efforts currently ongoing to understand their efficacy in patients will make it possible to assess whether A2A receptor blockers are a new interesting class of antiparkinsonian agents. Drug Dev. Res. 52:379–386, 2001. © 2001 Wiley‐Liss, Inc.
Transnatal olfactory continuity in the rabbit: Behavioral evidence and short‐term consequence of its disruption
Authors: Coureaud Gérard , Schaal Benoist , Hudson Robyn , Orgeur Pierre , Coudert Pierre 
Published: August 2002

AbstractThis study investigates the role of prenatal odor learning on postnatal adaptive orientation responses in the newborn rabbit. Preference tests revealed that pups are equally attracted to the odors of placentae and colostrum (Experiments 1–4), suggesting that an odor continuity may exist between the fetal and neonatal environments. To test some predictions derived from this hypothesis, we manipulated the odor of the diet of pregnant‐lactating does to control the chemical niches of their perinates. Fetuses exposed in this way to the odor of cumin (C) were selectively attracted as neonates to the odor of pure C (Experiment 6). Prenatal exposure to C also was followed, to a certain extent, by enhanced attraction to C odor in the placenta or colostrum from females which had consumed it (Experiments 5 & 7). Finally, the functional implications of perinatal odor continuity were tested by disrupting it. The odor component of the feto–neonatal transitional environment revealed indeed to affect the ability of certain pups to gain colostrum and milk at the very first sucking opportunities (Experiment 8). © 2002 Wiley Periodicals, Inc. Dev Psychobiol 40: 372–390, 2002. Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/dev.10038
Regulation of cognitive activity and early communication development in young autistic, mentally retarded, and young normal children
Authors: Adrien Jean‐Louis , Rossignol‐Deletang Nathalie , Martineau Joëlle , Couturier Guylène , Barthelemy Catherine 
Published: August 2002

AbstractBased on the Piagetian framework, this study examined regulation of cognitive activity and developmental communication profiles and their interrelationship in groups of autistic, mentally retarded, and normal children of comparable overall, verbal, and oculo‐manual developmental ages (from 6 to 24 months). Regulation of activity was assessed with both an object permanence test and an original behavior grid, and development of communication skills with the Guidetti‐Tourrette scales (French adaptation of the Seibert‐Hogan scales). The results showed evidence of certain types of dysregulation of cognitive activity and a general delay in communication ability in autistic children compared to the other two groups. Moreover, although the intensity of some of these disorders decreased in relation to the developmental levels of social interaction and joint attention in normal children, they were related to both high and low levels of development of social interaction only in autistic children. These findings raise the hypothesis of a relationship between a disorder of disengaging from an activity and developmental levels of social interaction noted at two transitory periods of early development (12 and 24 months) only in children with autism. Developmental and neuropsychological interpretations of this particular pattern are proposed. © 2001 John Wiley & Sons, Inc. Dev Psychobiol 39: 124–136, 2001
No evidence for SEL1L as a candidate gene for IDDM11‐conferred susceptibility
Authors: Pociot Flemming , Larsen Zenia M. , Zavattari Patrizia , Deidda Elisabetta , Nerup Jørn , Cattaneo Monica , Chiaramonte Raffaella , Comi Paola , Sabbadini Marta , Zollo Massimo , Biunno Ida , Cucca Francesco 
Published: August 2002

AbstractBackgroundThe SEL1L gene is located on human chromosome 14q24.3‐31 close to D14S67 which has been previously proposed to be a type 1 diabetes mellitus locus (IDDM11). Sel‐1 is a negative regulator of the Notch signalling pathway and SEL1L is selectively expressed in adult pancreas and islets of Langerhans. This suggests that SEL1L may be a candidate gene for IDDM11.MethodsWe have analysed two newly identified CA‐repeat polymorphisms within the genomic sequence of the SEL1L locus for association with type 1 diabetes mellitus (T1DM) in 152 Danish T1DM‐affected sib‐pair families and in 240 Sardinian families (229 simplex and 11 sib‐pair families).ResultsNo evidence for association of the two SEL1L markers with T1DM was observed in either the Danish or the Sardinian families. We have also used allelic sharing methods to analyse linkage with T1DM in the IDDM11 region using the same markers and the Danish collection of affected sib‐pair families. No evidence of linkage was observed (Zmax=0.86).ConclusionAlthough several lines of evidence suggest that SEL1L might be a candidate for IDDM11‐conferred susceptibility to T1DM the present study does not support this hypothesis. Copyright © 2001 John Wiley & Sons, Ltd.
Effects of acipimox on the lipolysis rate in subcutaneous adipose tissue of obese subjects
Authors: Flechtner‐Mors M. , Jenkinson C. P. , Alt A. , Adler G. , Ditschuneit H. H. 
Published: August 2002

AbstractBackgroundAcipimox is a hypolipidaemic agent reducing serum concentrations of triglycerides and non‐esterified fatty acids. Acipimox may reduce triglyceride synthesis by decreasing non‐esterified fatty acid availability from adipocytes, but this effect has yet to be demonstrated in vivo. Lipolysis after acipimox treatment was examined in subcutaneous adipose tissue of severely obese subjects with associated metabolic disorders.MethodsThe microdialysis technique was performed in abdominal subcutaneous adipose tissue of eight hyperinsulinaemic subjects. After oral treatment with acipimox, glycerol concentration was determined as an index of lipolysis rate. Blood flow was assessed by the ethanol escape technique. The rates of release of glycerol from human adipose tissue maximally stimulated by norepinephrine were also investigated in the presence of acipimox. Eight weight‐ and age‐matched subjects served as a control group.ResultsUnder acipimox treatment, basal glycerol release decreased in subcutaneous adipose tissue, whereas no effect was observed on blood flow. In stimulated adipose tissue acipimox showed no effect.ConclusionIn the present study basal glycerol outflow from adipose tissue was inhibited by acipimox. The anti‐lipolytic action of the agent may diminish elevated plasma concentrations of free fatty acids in subjects with severe obesity. Copyright © 2001 John Wiley & Sons, Ltd.
Eye defects in receptor protein‐tyrosine phosphatase α knock‐down zebrafish
Authors: Van Der Sar Astrid M. , Živković Danica , Den Hertog Jeroen 
Published: August 2002

AbstractReceptor protein‐tyrosine phosphatase alpha (RPTPα) is highly expressed in the developing retina of different species, but little is known about its function there. Here, we report that injection of antisense morpholinos in zebrafish embryos reduced RPTPα expression to almost nondetectable levels up to 3 days postfertilization (dpf). RPTPα was detectable again from 4 dpf onward. RPTPα knock‐down resulted in smaller eyes. Examination of sections of the retina at different developmental stages demonstrated that already at 28 hours postfertilization (hpf) fewer cells were present in the retina of RPTPα‐morpholino–injected embryos. At 3 dpf, the layered organization of the retina was absent. In addition, the morphology and labeling with an axon specific antibody, acetylated tubulin, demonstrated that most cells appeared to be undifferentiated. Strikingly, at 5 dpf the lamination of the retina was partially restored, concomitant with re‐expression of RPTPα protein. Although cells in the retina were now differentiated, the layering of the retina remained disrupted and significant gaps were observed in the amacrine cell layer. Therefore, knock‐down of RPTPα protein provides evidence that RPTPα is essential for normal retinal development. © 2002 Wiley‐Liss, Inc.