bluuebunny/crossref_metadata_2025_split huggingface dataset:
Segmentation defects of Notch pathway mutants and absence of a synergistic phenotype in lunatic fringe/radical fringe double mutant mice
Authors: Zhang Nian , Norton Christine R. , Gridley Thomas 
Published: August 2002

AbstractSummary: The Notch signaling pathway is important in regulating formation and anterior‐posterior patterning of somites in vertebrate embryos. Here we show that distinct segmentation defects are displayed in embryos mutant for the Notch pathway genes Notch1, Lunatic fringe (Lfng), Delta‐like 1 (Dll1), and Delta‐like 3 (Dll3). Lfng‐deficient mice and Dll3‐deficient mice exhibit very similar defects, and marker analysis suggests that progression of the segmentation clock is disrupted in Dll3 mutants. We also show that Radical fringe (Rfng)‐deficient mice exhibit no obvious phenotypic defects. To assess whether the absence of a phenotype in Rfng‐deficient mice was the result of functional redundancy with the Lfng gene, we generated Lfng/Rfng double homozygous mutant mice. These mice exhibit the skeletal defects normally observed in Lfng‐deficient mice, but we detected no obvious synergistic or additive effects in the double mutant animals. genesis 33:21–28, 2002. © 2002 Wiley‐Liss, Inc.
A transgenic insertion causing cryptorchidism in mice
Authors: Overbeek Paul A. , Gorlov Ivan P. , Sutherland Richard W. , Houston John B. , Harrison Wilbur R. , Boettger‐Tong Holly L. , Bishop Colin E. , Agoulnik Alexander I. 
Published: August 2002

AbstractSummary: A distinctive feature of gonadal maturation in mammals is the movement to an extraabdominal location. Testicular descent is a complex, multistage process whereby the embryonic gonads migrate from their initial abdominal position to the scrotum. Failure in this process results in cryptorchidism, a frequent congenital birth defect in humans. We report here a new mouse transgenic insertional mutation, cryptorchidism with white spotting (crsp). Males homozygous for crsp exhibit a high intraabdominal position of the testes, associated with complete sterility. Heterozygous males have a wild‐type phenotype, and homozygous females are fertile. Surgically descended testes in crsp/crsp males show normal spermatogenesis. Using FISH and genetic analyses, the transgenic insert causing the crsp mutation has been mapped to the distal part of mouse chromosome 5. Transgene integration resulted in a 550‐kb deletion located upstream of the Brca2 gene. A candidate gene encoding a novel G protein‐coupled receptor (Great) with an expression pattern suggesting involvement in testicular descent has been identified. genesis 30:26–35, 2001. © 2001 Wiley‐Liss, Inc.
Caveolin‐1 expression is maintained in rat and human astroglioma cell lines
Authors: Cameron Patricia L. , Liu Changdan , Smart Deedee K. , Hantus Stephen T. , Fick James R. , Cameron Richard S. 
Published: August 2002

AbstractCaveolin‐1 is the principal structural and functional component of caveolae, a plasmalemmal compartment that has been proposed to sequester lipid and protein components that participate in transmembrane signal transduction processes. Multiple studies reveal a reduction in the expression level of caveolin‐1 mRNA and protein in many carcinomas as well as transformed cells. The human caveolin‐1 gene is localized to a suspected tumor suppressor locus (7q31.1). Collectively, these data have been taken to imply that caveolin‐1 may function in a tumor suppressor capacity. To determine if a reduction in the expression level of caveolin‐1 mRNA and protein accompanied the transformation of astrocytes, we undertook studies of two transformed rat astroglial cell lines, C6 and DI TNC1, as well as several cell lines derived from human glioblastoma tumors: T98G, U87MG, U118MG, U138MG, and U373MG. Ultrastructural, immunolocalization, immunoblot, and Northern blot analyses demonstrated that caveolin‐1 message and protein were expressed in all rat and human glioma cells. The localization pattern, buoyant density, and detergent‐insolubility property of caveolin‐1 protein were indistinguishable from that determined for nontransformed type 1 astrocytes in culture. Nucleotide sequence analyses of caveolin‐1 cDNAs indicate that mutations are not present in the caveolin‐1 sequence in any of the glioma cell types. Taken together with previous analyses, these data indicate that, at least for astrocytes, the process of transformation in and of itself is not solely sufficient to reduce the level of caveolin‐1 expression, and that caveolin‐1 expression in and of itself is not solely sufficient to prevent the acquisition of a transformed phenotype. GLIA 37:275–290, 2002. © 2002 Wiley‐Liss, Inc.
Platelet‐activating factor induces cell death in cultured astrocytes and oligodendrocytes: Involvement of caspase‐3
Authors: Hostettler Mary Ellen , Knapp Pamela E. , Carlson Sonia L. 
Published: August 2002

AbstractThe biologically active lipid metabolite, platelet‐activating factor (PAF), is thought to contribute to inflammatory processes and tissue damage in a variety of central nervous system (CNS) injuries. In previous studies, we found that after contusion spinal cord injury, treatment with a PAF antagonist led to significantly increased white matter tissue sparing as well as decreased mRNA levels for pro‐inflammatory cytokines. Some studies suggest that PAF can also have toxic effects on neurons in vitro. Few studies, however, have examined the effects of PAF on glial cells of the CNS. In the present study, the potential for PAF to act as a toxin to cultured astrocytes was examined. Also investigated were the effects of PAF on oligodendrocytes at two different stages of development. Treatment with 0.02–2 μM PAF for 72 h resulted in significant levels of cell death in both cell types (P < 0.05), an effect that was blocked by the PAF receptor antagonists, WEB 2170 and BN 52021. To investigate PAF‐induced glial cell death further, we looked for activation of the enzyme, caspase‐3, which can be indicative of apoptosis. Immunocytochemistry demonstrated that PAF at all concentrations caused activation of caspase‐3 at 24, 48, and 72 h after treatment in both cell types. Caspase‐3‐dependent cell death was further confirmed using knockout mice (−/−) deficient in the caspase‐3 gene. Toxicity was lost when astrocytes (−/−) were exposed to 0.02–2 μM PAF (P < 0.01). Oligodendrocytes (−/−) were not susceptible to toxicity at 2 μM PAF (P < 0.001). The results demonstrate that the pro‐inflammatory molecule, PAF, induces cell death in cultured CNS glial cells and that this effect is, in part, dependent on caspase‐3 activation. GLIA 38:228–239, 2002. © 2002 Wiley‐Liss, Inc.
RANTES stimulates inflammatory cascades and receptor modulation in murine astrocytes
Authors: Luo Yi , Berman Michael A. , Zhai Qiwei , Fischer Falko R. , Abromson‐Leeman Sara R. , Zhang Ye , Kuziel William A. , Gerard Craig , Dorf Martin E. 
Published: August 2002

AbstractCultured mouse astrocytes respond to the CC chemokine RANTES by production of chemokine and cytokine transcripts. Stimulation of astrocytes with 1 nM RANTES or 3–10 nM of the structurally related chemokines (eotaxin, macrophage inflammatory protein‐1α and ‐β [MIP‐1α, MIP‐1β]) induced transcripts for KC, monocyte chemoattractant protein‐1 (MCP‐1), tumor necrosis factor‐α (TNF‐α), MIP‐1α, MIP‐2, and RANTES in a chemokine and cell‐specific fashion. Synthesis of chemokine (KC and MCP‐1) and cytokine (TNF‐α) proteins was also demonstrated. RANTES‐mediated chemokine synthesis was specifically inhibited by pertussis toxin, indicating that G‐protein‐coupled chemokine receptors participated in astrocyte signaling. Astrocytes expressed CCR1 and CCR5 (the redundant RANTES receptors). Astrocytes derived from mice with targeted mutations of either CCR1 or CCR5 respond after RANTES stimulation, suggesting multiple chemokine receptors may separately mediate RANTES responsiveness in astrocytes. Preliminary data suggest activation of the MAP kinase pathway is also critical for RANTES‐mediated signaling in astrocytes. Treatment with RANTES specifically modulated astrocyte receptors upregulating intercellular adhesion molecule 1 (ICAM‐1) and downregulating CX3CR1 expression. Thus, after chemokine treatment, astrocytes release proinflammatory mediators and reprogram their surface molecules. The combined effects of RANTES may serve to amplify inflammatory responses within the central nervous system. GLIA 39:19–30, 2002. © 2002 Wiley‐Liss, Inc.
Astrocytes in adult rat brain express type 2 inositol 1,4,5‐trisphosphate receptors
Authors: Holtzclaw Lynne A. , Pandhit Siddhesh , Bare Dan J. , Mignery Gregory A. , Russell James T. 
Published: August 2002

AbstractAstrocytes respond to neuronal activity by propagating Ca2+ waves elicited through the inositol 1,4,5‐trisphosphate pathway. We have previously shown that wave propagation is supported by specialized Ca2+ release sites, where a number of proteins, including inositol 1,4,5‐trisphosphate receptors (IP3R), occur together in patches. The specific IP3R isoform expressed by astrocytes in situ in rat brain is unknown. In the present report, we use isoform‐specific antibodies to localize immunohistochemically the IP3R subtype expressed in astrocytes in rat brain sections. Astrocytes were identified using antibodies against the astrocyte‐specific markers, S‐100β, or GFAP. Dual indirect immunohistochemistry showed that astrocytes in all regions of adult rat brain express only IP3R2. High‐resolution analysis showed that hippocampal astrocytes are endowed with a highly branched network of processes that bear fine hair‐like extensions containing punctate patches of IP3R2 staining in intimate contact with synapses. Such an organization is reminiscent of signaling microdomains found in cultured glial cells. Similarly, Bergmann glial cell processes in the cerebellum also contained fine hair‐like processes containing IP3R2 staining. The IP3R2‐containing fine terminal branches of astrocyte processes in both brain regions were found juxtaposed to presynaptic terminals containing synaptophysin as well as PSD 95‐containing postsynaptic densities. Corpus callosum astrocytes had an elongated morphology with IP3R2 studded processes extending along fiber tracts. Our data suggest that PLC‐mediated Ca2+ signaling in astrocytes in rat brain occurs predominantly through IP3R2 ion channels. Furthermore, the anatomical arrangement of the terminal astrocytic branches containing IP3R2 ensheathing synapses is ideal for supporting glial monitoring of neuronal activity. GLIA 39:69–84, 2002. Published 2002 Wiley‐Liss, Inc.
Inducible ablation of astrocytes shows that these cells are required for neuronal survival in the adult brain
Authors: Cui Wei , Allen Nicholas D. , Skynner Michael , Gusterson Barry , Clark A. John 
Published: August 2002

AbstractTo study the function of astrocytes in the adult brain, we have targeted the expression of E. coli nitroreductase (NTR) to the astrocytes of transgenic mice under the control of the GFAP promoter. The astrocytes expressing NTR were selectively ablated after administration of the prodrug CB1954, resulting in motor discoordination. Histological examination showed that the region most affected in the brain was the cerebellum, in which the Bergmann glia were eliminated and the granular neurons had degenerated. Specific effects were also noted on the dendrites of the Purkinje cells, and the junction between these neurons and granular layer was disrupted. Astrocyte ablation was associated with a dramatic decrease in the expression of glutamate transporters, which may account for the degeneration of granular neurons since the excitotoxic effects of glutamate result in a similar phenotype. These results provide the first evidence that astrocytes are important for the survival of neurons in the adult brain in vivo. GLIA 34:272–282, 2001. © 2001 Wiley‐Liss, Inc.
New tools to trace populations of inflammatory cells in the CNS
Authors: Flügel Alexander , Bradl Monika 
Published: August 2002

AbstractCells of the central nervous system (CNS) and immune system communicate regularly. There is a constant surveillance of the intact, healthy CNS by activated T‐cells, and massive infiltration of the CNS by immune cells under pathological conditions such as neurodegeneration or neuroinflammation. Labeling CNS‐infiltrating T‐cells is an essential tool to identify the signals and mechanisms, which mediate the interaction between immune cells and cells of the CNS. In this article, we will present an overview describing currently used cellular markers and demonstrate how these markers have contributed to our current knowledge of CNS inflammation and immune surveillance. GLIA 36:125–136, 2001. © 2001 Wiley‐Liss, Inc.
Cognitive impairment and functional status in elderly institutionalized patients with schizophrenia
Authors: Kurtz Matthew M. , Moberg Paul J. , Mozley Lyn Harper , Hickey Thomas , Arnold Steven E. , Bilker Warren B. , Gur Raquel E. 
Published: August 2002

AbstractObjectiveThe relationship of cognitive impairment to functional status in older adults with schizophrenia was investigated.PatientsNinety‐three psychiatric inpatients with schizophrenia between the ages of 65 and 88 years. Two subsets of this sample, consisting of 48 and 24 patients, were studied with a greater number of assessment instruments.MeasuresThe Mini‐Mental State Examination (MMSE) was used for brief assessment of overall cognitive functioning, and the Psychogeriatric Dependency Rating Scale (PGDRS) was administered to assess functional status. The cognitive test battery from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) and/or an expanded neuropsychological battery, was given to a subset of the patients.ResultsIn the overall sample, patients with greater global cognitive impairment had higher levels of rated impairment on the individual items that comprised the Orientation and Physical, but not Behavior, subscales of the PGDRS. Furthermore, in the two subsamples, specific neuropsychological measures of problem‐solving, word list learning, naming and constructional praxis were related to overall measures of outcome.ConclusionsNeuropsychological deficit and psychosocial outcome are multi‐dimensional entities that relate to one another in complex ways. Copyright © 2001 John Wiley & Sons, Ltd.
Frequency of behavioral symptoms characterizes agitation in Alzheimer's disease
Authors: Tractenberg Rochelle E. , Gamst Anthony , Weiner Myron F. , Koss Elisabeth , Thomas Ronald G. , Teri Linda , Thal Leon 
Published: August 2002

AbstractThis study describes two well‐characterized groups of Alzheimer's disease (AD) patients with similar levels of cognitive functioning, but with different overall behavioral disturbance levels. We sought to determine the nature of this difference—whether AD patients with higher levels of behavioral disturbance (n = 148) differ from less disturbed AD patients (n = 235) in terms of (a) the range of symptoms exhibited, (b) the frequency of occurrence of these symptoms, or (c) both of these. We defined and operationalized ‘diversity of behaviors’ and ‘frequency’ with respect to the item‐level responses on the Cohen‐Mansfield agitation inventory (CMAI). We found that, in these two samples of AD patients, differences occurred in the frequency of 10 out of 21 behaviors, rather than in a variety of endorsed behaviors. These 10 behaviors, observed at different frequencies in both groups, may be useful for monitoring change in studies of drugs or behavioral interventions for behavioral disturbance in persons with AD. Copyright © 2001 John Wiley & Sons, Ltd.
Social isolation predicts re‐hospitalization in a group of older American veterans enrolled in the UPBEAT Program
Authors: Mistry Ritesh , Rosansky Joel , McGuire Jim , McDermott Charles , Jarvik Lissy 
Published: August 2002

AbstractObjectivesDoes social isolation predict re‐hospitalization in a group of older men enrolled in Unified Psychogeriatric Biopsychosocial Evaluation and Treatment (UPBEAT), a mental health care‐coordination project at nine Veterans Affairs Healthcare Centers nationwide?MethodsThe current study examined 123 UPBEAT patients located at West Los Angeles, whose ratings were available on the Lubben Social Network Scale (LSNS), the SF‐36 scale, the Cumulative Illness Rating Scale (CIRS) and the Mental Health Index (MHI‐38) Depression and Anxiety subscales. Within one year of enrollment, 55% of patients were re‐hospitalized. Odds of re‐hospitalization were calculated using two logistic regression models. Social isolation risk (LSNS) and demographic covariates were included. In addition, Model 1 contained depression and anxiety measures (MHI‐38) and physician‐rated medical burden (CIRS), while in Model 2, patient‐perceived physical (PCS) and mental health (MCS) subscales from the SF‐36 were included.ResultsThe group of patients who were socially isolated or at high or moderate risk for isolation, were 4–5 times more likely to be re‐hospitalized within the year, than low isolation risk patients. In both Models 1 (chi‐square = 19.86; p = 0.031) and 2 (chi‐square = 26.42; p = 0.002) demographic characteristics were not significant predictors of re‐hospitalization, but social isolation risk was a significant predictor (Model 1: odds ratio (OR) = 5.31; 95% confidence intervals (CI) = 1.81–15.53; and Model 2: OR = 3.86; 95% CI = 1.39–10.73). In addition, MHI‐Anxiety was a significant predictor (OR = 1.22; 95% CI = 1.05–1.43) in Model 1 and in Model 2, patient‐perceived physical health significantly predicted re‐hospitalization (OR = 0.91; 95% CI = 0.86–0.96).ConclusionWhen controlling for other covariates, social isolation, physical health and mental health were significant risk factors for re‐hospitalization. These findings underline the importance of assessing and addressing lack of social support, along with other factors, in the health care of older male veterans. Copyright © 2001 John Wiley & Sons, Ltd.
Depression, cognitive impairment and function in Alzheimer's disease
Authors: Espiritu Doree Ann V. , Rashid Harun , Mast Benjamin T. , Fitzgerald Joe , Steinberg Joel , Lichtenberg Peter A. 
Published: August 2002

AbstractDepression is very common in patients with dementia but the relationship is very complex. Depression is regarded as a cause of excess disability in persons with dementia and contributes to their functional decline. The assessment of depression in dementia patients, however, has been difficult in that the validity of self‐reported depression in patients with dementia has been questioned. This study was done to investigate whether self‐reported depression by persons with dementia (using the GDS) is related to their functional abilities as rated by a family caregiver (using the IADL scale) above and beyond demographic variables. This study was conducted at the Detroit Satellite of the Michigan Alzheimer's Disease Research Center. There were 141 participants, 67% were African American and 33% were European American. Statistical analyses included a correlational and multiple regression approach to determine the predictive relationships of cognitive and depressive symptoms above and beyond the influence of demographic variables and cognition. The results of the study further support the notion that depression in dementia is significantly related to functional decline but, more importantly, that self‐reported depression in patients with dementia can be valuable information in understanding patients' functioning. Copyright © 2001 John Wiley & Sons, Ltd.
Apolipoprotein E ε4 allele is not associated with the cognitive impairment in community‐dwelling normal elderly individuals
Authors: Kim K. W. , Youn J. C. , Jhoo J. H. , Lee D. Y. , Lee K. U. , Lee J. H. , Woo J. I. 
Published: August 2002

AbstractObjectivesThe aim of this study was to examine whether the APOE ε4 allele also confers a risk for the cognitive impairment in normal aging.MethodsWe administered all the eight neuropsychological tests from the CERAD neuropsychological battery to the CVD‐free, community‐dwelling normal elderly individuals, and compared their performance by the occurrence of the APOE ε4 allele.ResultsEither the impact of APOE ε4 allele itself or its interaction terms with age and gender of the subjects did not influence the performance of the eight neuropsychological tests (εp > 0.1 by ANCOVA).ConclusionsThe APOE ε4 allele is not a risk factor for the cognitive decline in normal elderly individuals regardless of age and gender. Copyright © 2002 John Wiley & Sons, Ltd.
Paradigm‐dependent modulation of event‐related fMRI activity evoked by the oddball task
Authors: Clark Vincent P. , Fannon Sean , Lai Song , Benson Randall 
Published: August 2002

AbstractWe have previously shown that event‐related functional magnetic resonance imaging (ER‐fMRI) may be used to record responses to the rapid, interleaved presentation of stimuli in the three‐stimulus oddball task. The present study examined the sensitivity of ER‐fMRI responses to variations in the range of inter‐stimulus intervals (ISIs, calculated as the time from the offset of one stimulus to the onset of the next stimulus) and the type of behavioral response task used. ISIs were varied between a wide ISI range (550–2,050 msec) and a narrow ISI range (800–1,200 msec), while maintaining a similar mean ISI (approximately 1 stimulus per sec) between experiments. The response task was varied between button press and subvocal target counting. Gradient echo, echo planar images were acquired for each of three experiments (wide ISI with button press, narrow ISI with button press, and wide‐ISI with counting) in five subjects. Target stimuli generated increased fMRI signal in a wide range of brain regions. The use of a narrow ISI range generated a greater volume of subcortical activity and a reduced volume of cortical activity relative to a wide ISI range. The counting task generated a larger amplitude and longer lasting evoked response in brain regions that responded during all three experiments. Rare distractor stimuli evoked fMRI signal change primarily in orbitofrontal, ventral‐medial prefrontal and superior parietal cortex. These results illustrate that although ER‐fMRI is relatively insensitive as a technique to small variations in the timing of stimulus‐evoked responses, it is remarkably sensitive to consequences such variations have for the topographic location and amplitude of neural responses to stimuli. Hum. Brain Mapping 14:116–127, 2001. © 2001 Wiley‐Liss, Inc.
Recognizing diversity in public preferences: The use of preference sub‐groups in cost‐effectiveness analysis
Authors: Sculpher Mark , Gafni Amiram 
Published: August 2002

AbstractPublic preferences are typically incorporated into cost‐effectiveness analyses (CEA) on the basis of the average health state utilities of a sample of individuals drawn from the general public. The cost‐effectiveness of a programme is then assessed on an ‘all‐or‐nothing’ basis: the programme is declared either cost‐effective or not for all patients in clinically homogenous sub‐groups. However, this approach fails to recognize variability between individuals in their preferences. In this paper, we consider how diversity in the preferences of individuals can be handled within CEA when the public's preferences are considered appropriate for defining benefit, with the objective of increasing the efficiency of health care delivery. The concept of preference sub‐group analysis is described and some of its implications are assessed. These include the methods that could be used to identify sub‐groups from amongst public raters, the appropriate approach to eliciting preferences and the possible implications of preference sub‐group analysis for clinical decision making. Copyright © 2001 John Wiley & Sons, Ltd.