bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening of Dementia in Stroke Patients With Lacunar Infarcts: Comparison of the Mattis Dementia Rating Scale and the Mini-Mental State Examination
Authors: Tang Wai Kwong , Mok Vincent , Chan Sandra S. M. , Chiu Helen F. K. , Wong Ka Sing , Kwok Timothy C. Y. , Lam Wynnie W. M. , Ungvari Gabor S.
Published: January 2005

There have been no data on the performance of the Initiation-Perseveration subtest of the Mattis Dementia Rating Scale (MDRS-IP) in screening poststroke dementia (PSDE). Three months after the index stroke, a research assistant administered the MDRS-IP and Mini-Mental State Examination (MMSE) to 83 Chinese stroke patients with lacunar infarcts who were consecutively admitted to the stroke unit of a general hospital. A psychiatrist, who was blind to the MDRS-IP and MMSE scores, interviewed all 83 patients and made a Diagnostic and Statistical Manual of Mental Disorders (4th edition) diagnosis of dementia, which served as the benchmark for judging the performance of MDRSIP. The optimal cutoff point of MDRS-IP was 22/23. The sensitivity, specificity, and positive and negative predictive values of MDRS-IP, and the area under the receiver operating characteristic curve were 82%, 90%, 0.41, 0.98, and 0.91, respectively. The overall performance of the MDRS-IP was comparable to the MMSE. ( J Geriatr Psychiatry Neurol 2005;18:3-7)
Tolerability and Effectiveness of Lamotrigine in Complex Elderly Patients
Authors: Aulakh Jasdeep S. , Hawkins James W. , Athwal Herman S. , Sheikh Javaid I. , Yesavage Jerome , Tinklenberg Jared R.
Published: January 2005

There is paucity of medical literature on the use of lamotrigine in elderly patients who have behavior problems and diverse psychiatric syndromes. This article is a retrospective case series summarizing the authors’ experience with this medication. In a 20-patient case series from an institutional review board-approved retrospective chart review, the tolerability and efficacy of lamotrigine was evaluated for the management of agitated and aggressive behaviors in nursing home patients with a range of psychiatric and medical diagnoses. Nineteen of the elderly nursing home patients tolerated lamotrigine treatment, and 18 showed modest clinical improvement. These results support the authors’ belief that controlled clinical investigations of this medication should be performed. ( J Geriatr Psychiatry Neurol 2005; 18:8-11)
Impaired Comprehension of Affective Prosody in Elderly Subjects Is Not Predicted by Age-Related Hearing Loss or Age-Related Cognitive Decline
Authors: Orbelo Diana M. , Grim Michael A. , Talbott Richard E. , Ross Elliott D.
Published: January 2005

Impairments in the ability of elderly people to comprehend affective prosody have been reported, but little is known about the relationship between affective prosodic comprehension and age-related changes in hearing and cognition. The Aprosodia Battery, which included an assessment of attitudinal comprehension, was used to compare affective-prosodic comprehension in young and elderly subjects and to investigate the relationship of results to selected hearing and neuropsychological measures. As a group, the healthy elderly subjects were impaired relative to young subjects on all tasks assessing comprehension of affective prosody. Variability within the elderly group was not predicted by mild to moderate peripheral hearing loss and was only marginally predicted by traditional cognitive measures. These findings along with those of other researchers suggest that loss of affective-prosodic comprehension in elderly persons is related to a specific aging effect that impairs right hemisphere function. ( J Geriatr Psychiatry Neurol 2005; 18:25-32)
Vitamin C protects HL60 and U266 cells from arsenic toxicity
Authors: Karasavvas Nicos , Cárcamo Juan M. , Stratis George , Golde David W.
Published: January 2005

Although there is no compelling evidence that vitamin C has antitumor activity in humans, clinical trials are testing the hypothesis that ascorbic acid (AA) will enhance the efficacy of arsenic trioxide (As2O3) in myeloma. In vitro, AA cytotoxicity depends on its interaction with free transition metal ions in culture media leading to the generation of H2O2 and other reactive oxygen species (ROSs). Therefore, to circumvent the extracellular in vitro pro-oxidant effects of AA, we loaded HL60, U266, and RPMI-8226 cells with vitamin C by incubation with dehydroascorbic acid (DHA). Loading cells in this manner resulted in prominent, dose-dependent protection of As2O3-treated cells as measured by viability, colony formation, and apoptosis assays. Glutathione depletion enhanced cell sensitivity to the cytotoxic effects of As2O3 and vitamin C loading provided protection. AA was found to generate cytotoxic concentrations of H2O2 in culture medium without cells and copper/iron chelators inhibited this reaction. However, AA did not generate H2O2 in simple buffer or human plasma. Direct incubation with AA resulted in increased intracellular ROSs, whereas DHA incubation decreased it. These results clarify an apparent paradox and indicate that vitamin C loading in HL60, U266, and RPMI-8226 cells ameliorates As2O3 cytotoxicity.
CCAAT/enhancer binding protein ϵ: changes in function upon phosphorylation by p38 MAP kinase
Authors: Williamson Elizabeth A. , Williamson Ian K. , Chumakov Alexey M. , Friedman Alan D. , Koeffler H. Phillip
Published: January 2005

C/EBPϵ, a member of the CCAAT/enhancer binding protein family, is a transcription factor important in neutrophil differentiation. We have determined that it is phosphorylated on multiple serine and threonine residues and can be a target for phosphorylation by a number of kinases. We identified a threonine at amino acid 75, part of a consensus mitogen-activated protein (MAP) kinase site within the transactivation domain of C/EBPϵ, as being phosphorylated only by p38 MAP kinase. Phosphorylation of this residue resulted in enhanced transcriptional activity on a myeloid-specific promoter in in vitro transient transfection reporter assays. We also determined that phosphorylation at Thr75 yielded a protein that was more effective at binding its cognate DNA sequence compared with the wild-type nonphosphorylated C/EBPϵ. Stable expression of C/EBPϵT75A in interleukin 3 (IL-3)–dependent 32Dcl3 did not result in the up-regulation of expression of secondary granule genes compared with wild-type C/EBPϵ or C/EBPϵT75D. Therefore we suggest that C/EBPϵ is a target for p38 MAP kinase activity.
Bayesian and maximum likelihood phylogenetic analyses of protein sequence data under relative branch-length differences and model violation
Authors: Mar Jessica C , Harlow Timothy J , Ragan Mark A
Published: January 2005

Background

Bayesian phylogenetic inference holds promise as an alternative to maximum likelihood, particularly for large molecular-sequence data sets. We have investigated the performance of Bayesian inference with empirical and simulated protein-sequence data under conditions of relative branch-length differences and model violation.

Results

With empirical protein-sequence data, Bayesian posterior probabilities provide more-generous estimates of subtree reliability than does the nonparametric bootstrap combined with maximum likelihood inference, reaching 100% posterior probability at bootstrap proportions around 80%. With simulated 7-taxon protein-sequence datasets, Bayesian posterior probabilities are somewhat more generous than bootstrap proportions, but do not saturate. Compared with likelihood, Bayesian phylogenetic inference can be as or more robust to relative branch-length differences for datasets of this size, particularly when among-sites rate variation is modeled using a gamma distribution. When the (known) correct model was used to infer trees, Bayesian inference recovered the (known) correct tree in 100% of instances in which one or two branches were up to 20-fold longer than the others. At ratios more extreme than 20-fold, topological accuracy of reconstruction degraded only slowly when only one branch was of relatively greater length, but more rapidly when there were two such branches. Under an incorrect model of sequence change, inaccurate trees were sometimes observed at less extreme branch-length ratios, and (particularly for trees with single long branches) such trees tended to be more inaccurate. The effect of model violation on accuracy of reconstruction for trees with two long branches was more variable, but gamma-corrected Bayesian inference nonetheless yielded more-accurate trees than did either maximum likelihood or uncorrected Bayesian inference across the range of conditions we examined. Assuming an exponential Bayesian prior on branch lengths did not improve, and under certain extreme conditions significantly diminished, performance. The two topology-comparison metrics we employed, edit distance and Robinson-Foulds symmetric distance, yielded different but highly complementary measures of performance.

Conclusions

Our results demonstrate that Bayesian inference can be relatively robust against biologically reasonable levels of relative branch-length differences and model violation, and thus may provide a promising alternative to maximum likelihood for inference of phylogenetic trees from protein-sequence data.
Home visits by family physicians during the end-of-life: Does patient income or residence play a role?
Authors: Burge Frederick I , Lawson Beverley , Johnston Grace
Published: January 2005

Background

With a growing trend for those with advanced cancer to die at home, there is a corresponding increase in need for primary medical care in that setting. Yet those with lower incomes and in rural regions are often challenged to have their health care needs met. This study examined the association between patient income and residence and the receipt of Family Physician (FP) home visits during the end-of-life among patients with cancer.

Methods

Data Sources/Study Setting. Secondary analysis of linked population-based data. Information pertaining to all patients who died due to lung, colorectal, breast or prostate cancer between 1992 and 1997 (N = 7,212) in the Canadian province of Nova Scotia (NS) was extracted from three administrative health databases and from Statistics Canada census records. Study Design. An ecological measure of income ('neighbourhood' median household income) was developed using census information. Multivariate logistic regression was then used to assess the association of income with the receipt of at least one home visit from a FP among all subjects and by region of residency during the end-of-life. Covariates in the initial multivariate model included patient demographics and alternative health services information such as total days spent as a hospital inpatient. Data Extraction Methods. Encrypted patient health card numbers were used to link all administrative health databases whereas the postal code was the link to Statistics Canada census information.

Results

Over 45% of all subjects received at least one home visit (n = 3265). Compared to those from low income areas, the log odds of receiving at least one home visit was significantly greater among subjects who reside in middle to high income neighbourhoods (for the highest income quintile, adjusted odds ratio [OR] = 1.37, 95% confidence interval [CI] = 1.15, 1.64; for upper-middle income, adjusted OR = 1.19, 95%CI = 1.02, 1.39; for middle income, adjusted OR = 1.33, 95%CI = 1.15, 1.54). This association was found to be primarily associated with residency outside of the largest metropolitan region of the province.

Conclusion

The likelihood of receiving a FP home visit during the end-of-life is associated with neighbourhood income particularly among patients living outside of a major metropolitan region.
Maps of the Sri Lanka malaria situation preceding the tsunami and key aspects to be considered in the emergency phase and beyond
Authors: Briët Olivier JT , Galappaththy Gawrie NL , Konradsen Flemming , Amerasinghe Priyanie H , Amerasinghe Felix P
Published: January 2005

Background

Following the tsunami, a detailed overview of the area specific transmission levels is essential in assessing the risk of malaria in Sri Lanka. Recent information on vector insecticide resistance, parasite drug resistance, and insights into the national policy for malaria diagnosis and treatment are important in assisting national and international agencies in their control efforts.

Methods

Monthly records over the period January 1995 – October 2004 of confirmed malaria cases were used to perform an analysis of malaria distribution at district spatial resolution. Also, a focused review of published reports and routinely collected information was performed.

Results

The incidence of malaria was only 1 case per thousand population in the 10 months leading up to the disaster, in the districts with the highest transmission.

Conclusion

Although relocated people may be more exposed to mosquito bites, and their capacity to handle diseases affected, the environmental changes caused by the tsunami are unlikely to enhance breeding of the principal vector, and, given the present low parasite reservoir, the likelihood of a malaria outbreak is low. However, close monitoring of the situation is necessary, especially as December – February is normally the peak transmission season. Despite some losses, the Sri Lanka public health system is capable of dealing with the possible threat of a malaria outbreak after the tsunami. The influx of foreign medical assistance, drugs, and insecticides may interfere with malaria surveillance, and the long term malaria control strategy of Sri Lanka, if not in accordance with government policy.
CCL25 Enhances CD103‐Mediated Lymphocyte Adhesion to E‐Cadherin
Authors: ERICSSON ANNA , ARYA ANU , AGACE WILLIAM
Published: January 2005

Abstract: Our results demonstrate that (1) CD103 is upregulated on CD8+ T cells subsequent to their entry into the small intestinal epithelium, and (2) that the chemokine CCL25 enhances CD103‐mediated adhesion to E‐cadherin. These results suggest a novel role for chemokines in modulating interactions between lymphocytes and epithelial cells at mucosal surfaces.
Hyporesponsiveness of CD4 T Cells Induced in Oral Tolerance Is Maintained by Selective Impairment in the TCR‐Induced Calcium/NFAT Signaling Pathway Resulting from Caspase Activation
Authors: HACHIMURA SATOSHI , KAJI TOMOHIRO , ASAI KAZUMI , ISE WATARU , NAKAYAMA TOSHINORI , KAMINOGAWA SHUICHI
Published: January 2005

Abstract: We examined intracellular signaling of hyporesponsive CD4 T cells induced by continuous feeding with high‐dose antigen in a TCR transgenic mouse system. The results demonstrated a selective impairment in their TCR‐induced calcium/NFAT‐signaling pathway. Proteomic analysis revealed caspase activation in these cells, which resulted in cleavage of GADS. Further analysis of the TCR‐signaling complex showed that GADS‐LAT‐SLP‐76‐associated PLC‐γ1 was decreased in both phosphorylation and association. Thus, as a consequence of caspase activation, orally tolerant CD4 T cells could not form normal TCR signaling complexes associated with GADS and showed downregulated PLC‐γ1 activation, which resulted in impairment of TCR‐induced calcium signaling.
Stochastic Resonance‐Like Phenomena in the Context of the Alimentary Tract
Authors: SÁNCHEZ PABLO , LORENZO MÁXIMO , REWALD ENRIQUE
Published: January 2005

Abstract: External noisy stimulation induces Ca2+ binding protein dynamics synchronization. Cell coupling chain fluctuation may lead to internal order facilitating information (generation and propagation). Body rhythms require cellular synchronization by interaction between nonlinear biological systems in a fluctuating environment. Could stochastic resonance add or subtract efficacy in digestive tolerogenic selection or disease?
CD4+ CD25+ Regulatory T Cell Selection
Authors: CATON ANDREW J. , COZZO CRISTINA , LARKIN JOSEPH , LERMAN MELISSA A. , BOESTEANU ALINA , JORDAN MARTHA S.
Published: January 2005

Abstract: Accumulating evidence indicates that regulatory T cells play a crucial role in preventing autoimmunity. To examine the processes by which regulatory CD4+ T cells are produced during immune repertoire formation, we have developed transgenic mice that express the influenza virus hemagglutinin (HA) and coexpress major histocompatibility complex class II‐restricted T cell receptors (TCRs) with varying affinities for the HA‐derived CD4+ T cell determinant S1. We show that interactions with a single self‐peptide can induce thymocytes bearing an autoreactive TCR to undergo selection to become CD4+ CD25+ regulatory T cells, and that thymocytes bearing TCRs with low affinity for S1 do not undergo selection into this pathway. We show that CD4+ thymocytes with identical specificity for the S1 self‐peptide can undergo overt deletion versus abundant selection to become CD4+ CD25+ regulatory T cells in response to variations in expression of the S1 self‐peptide in different lineages of HA transgenic mice. We also show that CD4+ CD25+ T cells proliferate in response to their selecting self‐peptide in the periphery. Moreover, they do not proliferate in response to lymphopenia in the absence of the selecting self‐peptide, reflecting a low level of expression of the high‐affinity receptor for IL‐7 (CD127) relative to conventional CD4+ T cells. These studies are determining how specificity for self‐peptides directs the thymic selection and peripheral expansion of CD4+ CD25+ regulatory T cells. Moreover, the differing responsiveness of CD4+ CD25+ regulatory T cells to cytokine‐ versus self‐peptide‐mediated signals may direct their accumulation to sites where the self‐peptide is expressed.
Natural and Induced Regulatory T Cells
Authors: O'NEILL EMMA J. , SUNDSTEDT ANETTE , MAZZA GRAZIELLA , NICOLSON KIRSTY S. , PONSFORD MARY , SAURER LESLIE , STREETER HEATHER , ANDERTON STEVE , WRAITH DAVID C.
Published: January 2005

Abstract: Mucosal antigen delivery can induce tolerance, as shown by suppression of subsequent responses to antigen. Our previous work showed that both intranasal and oral routes of antigen delivery were effective but indicated that the intranasal route might be more reliable. Intranasal peptide administration induced cells that could mediate bystander suppression of responses to associated antigenic epitopes. Here, we discuss further investigation into the nature of intranasal, peptide‐induced tolerance. Cells from mice treated with intranasal peptide became anergic and shut down secretion of cytokines such as IL‐2, but still secreted IL‐10. This latter cytokine was required for suppression of immune responses in vivo even though suppression of responses in vitro was IL‐10 independent. Intranasal peptide induced a subset of CD25−, CTLA‐4+ regulatory cells that suppressed naive cell function in vitro and in vivo. We provide evidence that these cells arise from CD25− precursors and differentiate independently from natural CD25+ regulatory cells. IL‐10‐secreting regulatory cells are also found in the peripheral blood of humans and can be induced by soluble peptide administration. This route of tolerance induction offers promise as a means of antigen‐specific immunotherapy of allergic and autoimmune conditions in humans.
Early Upregulation of T Cell IL‐10 Production Plays an Important Role in Oral Tolerance Induction
Authors: CONG Y , LIU C , WEAVER C T , ELSON C O
Published: January 2005

Abstract: Early in oral tolerance induction, IL‐10‐producing CD4+ T cells were increased, and adoptive transfer of IL‐10‐deficient CD4+ T cells failed induction of oral tolerance, suggesting a key role of IL‐10 production in such a process.
Comparative study of Oral versus Subcutaneous B:9–23 insulin peptide in Balb/c mice as an experimental model for Autoimmune Diabetes
Authors: DEVENDRA DEVASENAN , PARONEN JOHANNA , LIU EDWIN , MORIYAMA HIROAKI , TAYLOR ROBERT , MIAO DONGMEI , YU LIPING , EISENBARTH GEORGE
Published: January 2005

Abstract: Insulin peptide B:9–23 (amino acids 9 to 23 of the B chain) can induce immune targeting of insulin and islets in normal Balb/c mice. The insulin autoantibodies induced react with insulin and not the immunizing peptide. Oral administration of insulin as well as subcutaneous insulin can sensitize to insulin.
Macrophage Migration Inhibitory Factor and Activator Protein‐1 in Ulcerative Colitis
Authors: ISHIGURO YOH , YAMAGATA KAZUFUMI , SAKURABA HIROTAKE , MUNAKATA AKIHIRO , NAKANE AKIO , MORITA TAKAYUKI , NISHIHIRA JUN
Published: January 2005

Abstract: Macrophage migration inhibitory factor (MIF) is a cytokine that has potent antisteroid effects. We determined that MIF is involved in the glucocorticoid‐resistant inflammatory process of ulcerative colitis (UC), and the altered AP‐1 signal is a potent therapeutic target for refractory UC.
Decreased Nasal Tolerance to Allergic Asthma in Mice Fed an Amino Acid‐Based Protein‐Free Diet
Authors: MUCIDA DANIEL SOUSA , RODRÍGUEZ DUNIA , KELLER ALEXANDRE CASTRO , GOMES ELIANE , MENEZES JUSCILENE SILVA , de FARIA ANA MARIA CAETANO , RUSSO MOMCHILO
Published: January 2005

Abstract: Intranasal (i.n.) administration of soluble proteins induces a state of specific unresponsiveness to subsequent immunization, known as nasal tolerance. It is thought that newborns are less susceptible to nasal tolerance induction. Recently, we have shown that feeding adult animals with a protein‐free diet (Aa) resulted in their arrest at an immature immunological profile. Here, we examined the effects of the Aa diet on the development of nasal tolerance to ovalbumin (OVA) in a murine model of allergic asthma. Nasal OVA administration suppressed almost totally the OVA‐induced asthma‐like responses (airway eosinophilia, type 2 cytokine production, and OVA‐specific IgE antibodies) in chow‐ or casein‐fed BALB/c mice. In contrast, in Aa‐fed animals the suppression of asthma‐like responses by nasal OVA was partial, being effective in suppressing airway eosinophilia, but not airway type 2 cytokine or OVA‐specific IgE response. We conclude that animals fed the Aa diet are more resistant to the induction of nasal tolerance. Our animal model may mimic the features of the immune system of human infants.
Long‐Term Follow‐Up of Oral Tolerance Induction with HLA‐Peptide B27PD in Patients with Uveitis
Authors: THURAU STEPHAN R. , FRICKE HARALD , BURCHARDI CHRISTIAN , DIEDRICHS‐MÖHRING MARIA , WILDNER GERHILD
Published: January 2005

Abstract: Oral tolerance induction with peptide B27PD had an ameliorating effect in uveitis patients, which was also observed in the five‐year follow‐up period. Repeated treatments with peptide B27PD were also effective. Side effects did not occur in this patient group, not even in patients receiving peptide for up to 42 weeks.
Constraints on the Efficacy of Mucosal Tolerance in Treatment of Human and Animal Arthritic Diseases
Authors: STAINES NORMAN A. , DERRY CATHERINE J. , MARINOVA‐MUTAFCHIEVA LILIA , ALI NADIRA , DAVIES D HUW , MURPHY JOHN J.
Published: January 2005

Abstract: Mucosal administration of an autoantigen has been shown to be a powerful way of inducing tolerance in both animal and human arthritis clinical trials. Bovine or chicken type II collagen has been administered orally to rheumatoid arthritis patients, resulting in some, although in many cases rather limited, clinical improvement. Animal studies have revealed that the mechanisms that underlie induction of mucosal tolerance include clonal deletion, suppression of the proinflammatory Th1 cells, and the induction of regulatory T cells. These cells, defined as a persistently CD25‐expressing subset of CD4+ cells, are frequently anergic, may produce anti‐inflammatory cytokines such as IL‐10 and TGF‐β, and are likely to be agents of bystander suppression. A key feature that may affect the induction of these cells and other suppressive mechanisms is the dose of antigen administered. The results from human clinical trials suggest a daily dose of significantly less than 1 mg is optimal. Similarly data from collagen‐induced arthritis studies reveal an optimal dose above and below which there is little or no immune suppression. Indeed, the incorrect dose can prime the immune response and aggravate disease. The timing and frequency of administration is also vital to the level of immune tolerance induced and the control of the pathological process. This and other findings derived from animal studies are discussed here in relation to the results from human clinical trials.
Carbenoxolone Induces Oxidative Stress in Liver Mitochondria, Which Is Responsible for Transition Pore Opening
Authors: Salvi Mauro , Fiore Cristina , Battaglia Valentina , Palermo Mario , Armanini Decio , Toninello Antonio
Published: January 2005

Carbenoxolone (Cbx), a derivative of glycyrrhetinic acid, which has been found to affect mineralocorticoid and glucocorticoid receptors, induces swelling and membrane potential collapse when added to Ca2+-loaded liver mitochondria at 10 μm concentrations.

These effects are strictly correlated with hydrogen peroxide generation, increase in oxygen uptake, and sulfhydryl and pyridine nucleotide oxidation. Cyclosporin A, bongkrekic acid, and N-ethylmaleimide completely abolish all the above-described effects, suggesting that Cbx can be considered an inducer of mitochondrial permeability transition by means of oxidative stress. Cbx can also trigger the apoptotic pathway because the above events are also correlated with the loss of cytochrome c. These effects are probably related to the conjugated carbonyl oxygen in C-11, which produces reactive oxygen species by interacting with the mitochondrial respiratory chain, mainly at the level of complex I but, most likely, also with complex III. The oxidative stress induced by Cbx, which is responsible for pore opening, excludes that this is related to a genomic effect of the compound.
Nestin-Immunoreactive Cells in Rat Pituitary Are neither Hormonal nor Typical Folliculo-Stellate Cells
Authors: Krylyshkina Olga , Chen Jianghai , Mebis Liese , Denef Carl , Vankelecom Hugo
Published: January 2005

Nestin is an intermediate filament protein that has originally been identified as a marker of neuroepithelial stem/progenitor cells. The present study explored whether nestin immunoreactivity (nestin-ir) is present in the rat pituitary and in which cell type(s). Nestin-ir was observed in scattered cells in the anterior, intermediate, and neural lobes. Nestin-ir cells were predominantly of stellate shape and were more numerous in immature than in adult animals. Nestin-ir did not colocalize with any pituitary hormone, and did not colocalize or only very sporadically with the folliculo-stellate cell marker S100. In the intermediate lobe, nestin-ir cells contained glial fibrillary acidic protein in an age-dependent manner. Nestin-ir cells were closely associated with endothelial and fibronectin-ir cells, but did mostly not coincide. Nestin-ir was not found in α-smooth muscle actin-ir myofibroblasts or in microglial cells. Regardless of age, nestin-ir was detected in some unidentifiable cells that border the pituitary cleft. Nestin-ir remained present in pituitary cultured as three-dimensional aggregates. Treatment with basic fibroblast growth factor or leukemia inhibitory factor increased the number of nestin-ir cells. Starting from anterior lobe cell monolayer cultures, nestin-ir cells could be selected and propagated to a virtually pure population. These nestin-ir cells displayed remarkable motility and proliferative activity, and did not express hormones, glial fibrillary acidic protein, or S100, but contained vimentin-, fibronectin-, and α-smooth muscle actin-ir. In conclusion, nestin-ir is present in the pituitary in cells that are neither hormonal nor typical folliculo-stellate. The expression pattern depends on age and lobe examined. Pericapillar localization suggests a pericyte phenotype for some of them. Whether the heterogeneous nestin-ir population also contains pituitary progenitor cells remains to be explored.
Adrenomedullin Stimulates Nitric Oxide Release from SK-N-SH Human Neuroblastoma Cells by Modulating Intracellular Calcium Mobilization
Authors: Xu Yong , Krukoff Teresa L.
Published: January 2005

We used SK-N-SH human neuroblastoma cells to test the hypothesis that adrenomedullin (ADM), a multifunctional neuropeptide, stimulates nitric oxide (NO) release by modulating intracellular free calcium concentration ([Ca2+]i) in neuron-like cells. We used a nitrite assay to demonstrate that ADM (10 pm to 100 nm) stimulated NO release from the cells, with a maximal response observed with 1 nm at 30 min. This response was blocked by 1 nm ADM22–52, an ADM receptor antagonist or 2 μm vinyl-l-NIO, a neuronal NO synthase inhibitor. In addition, 5 μm 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid acetoxymethyl ester, an intracellular calcium chelator, eliminated the ADM-induced NO release. Similar results were observed when the cells were incubated in calcium-free medium or when l-type calcium channels were inhibited with 5 μm nifedipine or 10 μm nitrendipine. Depletion of calcium stores in the endoplasmic reticulum (ER) with 1 μm cyclopiazonic acid or 150 nm thapsigargin, or inhibition of ryanodine-sensitive receptors in the ER with 10 μm ryanodine attenuated the ADM-induced NO release. NO responses to ADM were mimicked by 1 mm dibutyryl cAMP, a cAMP analog, and were abrogated by 5 μm H-89, a protein kinase A inhibitor. Furthermore, Fluo-4 fluorescence-activated cell sorter analysis showed that ADM (1 nm) significantly increased [Ca2+]i at 30 min. This response was blocked by nifedipine (5 μm) or H-89 (5 μm) and was reduced by ryanodine (10 μm). These results suggest that ADM stimulates calcium influx through l-type calcium channels and ryanodine-sensitive calcium release from the ER, probably via cAMP-protein kinase A-dependent mechanisms. These elevations in [Ca2+]i cause activation of neuronal NO synthase and NO release.
A Polymorphism in the 3′ Untranslated Region of the Gene for Tumor Necrosis Factor Receptor 2 Modulates Reporter Gene Expression
Authors: Puga Irene , Lainez Begoña , Fernández-Real José Manuel , Buxadé Maria , Broch Montserrat , Vendrell Joan , Espel Enric
Published: January 2005

The gene encoding the human TNFα receptor (TNFR) 2 contains polymorphisms in the 3′ untranslated region (UTR). Previous studies have shown that some variant alleles in this region are associated with obesity and insulin resistance. However, the effect of these polymorphisms on the expression of TNFR2 has not been studied to date. To examine the role played by different haplotypes in the control of TNFR2 expression (haplotypes A1-A5, referring to nucleotides 1663 G/A, 1668 T/G, and 1690 T/C), we introduced these sequences into the 3′-UTR of a heterologous reporter gene and expressed the corresponding constructs in a human T-cell line. We demonstrate that a 485-nt fragment of the TNFR2 3′-UTR that contains a U-rich region decreases reporter expression and that haplotypes A1-A4 exert a stronger effect than A5. Furthermore, time-course assays of mRNA stability using actinomycin D revealed that haplotypes A1-A4 destabilize the mRNA. The proximal TNFR2 3′-UTR, independently of haplotype differences, responded to T-cell activation by increasing mRNA decay. Electromobility shift analysis demonstrated that protein(s) found in T-cell extracts bind to the 485-nt fragment. We suggest that an increased rate of TNFR2 mRNA decay protects cells from unrestrained TNFα effects and that this protection is weakened in A5 subjects. These findings may explain the association of this haplotype with obesity and increased leptin levels.
Apelin, a Newly Identified Adipokine Up-Regulated by Insulin and Obesity
Authors: Boucher Jérémie , Masri Bernard , Daviaud Danièle , Gesta Stéphane , Guigné Charlotte , Mazzucotelli Anne , Castan-Laurell Isabelle , Tack Ivan , Knibiehler Bernard , Carpéné Christian , Audigier Yves , Saulnier-Blache Jean-Sébastien , Valet Philippe
Published: January 2005

The results presented herein demonstrate that apelin is expressed and secreted by both human and mouse adipocytes. Apelin mRNA levels in isolated adipocytes are close to other cell types present in white adipose tissue or other organs known to express apelin such as kidney, heart, and to a lesser extent brown adipose tissue. Apelin expression is increased during adipocyte differentiation stage. A comparison of four different models of obesity in mice showed a large increase in both apelin expression in fat cells and apelin plasma levels in all the hyperinsulinemia-associated obesities and clearly demonstrated that obesity or high-fat feeding are not the main determinants of the rise of apelin expression. The lack of insulin in streptozotocin-treated mice is associated with a decreased expression of apelin in adipocytes. Furthermore, apelin expression in fat cells is strongly inhibited by fasting and recovered after refeeding, in a similar way to insulin. A direct regulation of apelin expression by insulin is observed in both human and mouse adipocytes and clearly associated with the stimulation of phosphatidylinositol 3-kinase, protein kinase C, and MAPK. These data provide evidence that insulin exerts a direct control on apelin gene expression in adipocytes. In obese patients, both plasma apelin and insulin levels were significantly higher, suggesting that the regulation of apelin by insulin could influence blood concentrations of apelin. The present work identifies apelin as a novel adipocyte endocrine secretion and focuses on its potential link with obesity-associated variations of insulin sensitivity status.
Adenosine 5′-Monophosphate-Activated Protein Kinase and p38 Mitogen-Activated Protein Kinase Participate in the Stimulation of Glucose Uptake by Dinitrophenol in Adult Cardiomyocytes
Authors: Pelletier Amélie , Joly Érik , Prentki Marc , Coderre Lise
Published: January 2005

During metabolic stress, such as ischemia or hypoxia, glucose becomes the principal energy source for the heart. It has been shown that increased cardiac glucose uptake during metabolic stress has a protective effect on cell survival and heart function. Despite its physiological importance, only limited data are available on the molecular mechanisms regulating glucose uptake under these conditions. We used 2,4-dinitrophenol (DNP), an uncoupler of oxidative phosphorylation, as a model to mimic hypoxia and gain insight into the signaling pathway underlying metabolic stress-induced glucose uptake in primary cultures of rat adult cardiomyocytes. The results demonstrate that 0.1 mm DNP induces 2.2- and 9-fold increases in AMP-activated protein kinase (AMPK) and p38 MAPK phosphorylation, respectively. This is associated with a 2.3-fold increase in glucose uptake in these cells. To further delineate the role of AMPK in the regulation of glucose uptake, we used two complementary approaches: pharmacological inhibition of the enzyme with adenine 9-β-D arabinofuranoside and adenoviral infection with a dominant-negative AMPK (DN-AMPK) mutant. Our results show that overexpression of DN-AMPK completely suppressed DNP-mediated phosphorylation of acetyl coenzyme A carboxylase, a downstream target of AMPK. Inhibition of AMPK with either 9-β-D arabinofuranoside or DN-AMPK also abolished DNP-mediated p38 MAPK phosphorylation. Importantly, AMPK inhibition only partially decreased DNP-stimulated glucose uptake in cardiomyocytes. Inhibition of p38 MAPK with the pharmacological agent PD169316 also partially reduced (70%) glucose uptake in response to DNP. In conclusion, our results indicate that p38 MAPK acts downstream of AMPK in cardiomyocytes and that activation of the AMPK/p38 MAPK signaling cascade is essential for maximal stimulation of glucose uptake in response to DNP in adult cardiomyocytes.
Genomic Regions that Mediate Placental Cell-Specific and Developmental Regulation of Human Cyp19 (Aromatase) Gene Expression in Transgenic Mice
Authors: Kamat Amrita , Smith Margaret E. , Shelton John M. , Richardson James A. , Mendelson Carole R.
Published: January 2005

The human aromatase (hCYP19) gene is controlled by tissue-specific promoters that lie upstream of tissue-specific first exons. Placenta-specific exon I.1 lies approximately 100,000 bp upstream of exon II. Previously, we observed that genomic sequences within 501 bp upstream of exon I.1 mediate placenta-specific expression. In the present study, transgenic mice were created carrying hCYP19I.1−246:hGH/hGX, hCYP19I.1−201:hGH, and hCYP19I.1−125:hGH fusion genes to further delineate 5′-flanking sequences within 501 bp of exon I.1 that are required to mediate placenta-specific hCYP19 gene expression. As little as 246 bp of hCYP19 exon I.1 5′-flanking sequence was sufficient to direct placenta-specific expression in transgenic mice. By contrast, transgenes containing 201 or 125 bp of exon I.1 5′-flanking DNA were not expressed in mouse placenta. Furthermore, hCYP19I.1−246:hGX transgene expression was developmentally regulated; expression was observed as early as embryonic d 7.5 (E7.5) in several cells of the trophoblast ectoderm, on E8.5 in some trophoblast giant cells, and by E9.5 in giant cells and the labyrinthine layer. By contrast, expression of the hCYP19I.1−501:hGH transgene was first observed on E10.5 and was restricted to the labyrinthine layer, which is most analogous to the human syncytiotrophoblast. This suggests the presence of regulatory elements between −501 and −246 bp that may bind inhibitory transcription factors expressed in giant cells. These findings from transgenic experiments together with deletion mapping studies using transfected human placental cells indicate that the concerted interaction of strong placenta-specific enhancers and silencers within this 501-bp region mediate labyrinthine and syncytiotrophoblast-specific CYP19 gene expression.
The Differential Binding Affinities of the Luteinizing Hormone (LH)/Choriogonadotropin Receptor for LH and Choriogonadotropin Are Dictated by Different Extracellular Domain Residues
Authors: Galet Colette , Ascoli Mario
Published: January 2005

The high degree of amino acid sequence homology and the divergent ligand binding affinities of the rat (r) and human (h) LH receptors (LHRs) allowed us to identify amino acid residues of their extracellular domain that are responsible for the different binding affinities of bovine (b) and hLH, and human choriogonadotropin (hCG) to the hLHR and rLHR. Because of the proposed importance of the β-sheets of the leucine-rich repeats (LRRs) of the extracellular domain of the LHR on hormone binding, we examined 10 divergent residues present in these regions by analyzing two complementary sets of mutants in which hLHR residues were substituted with the corresponding rLHR residues and vice versa. These experiments resulted in the identification of a single residue (a Ile or Ser in the C-terminal end of LRR2 of the hLHR or rLHR, respectively) that is important for hLH binding affinity. Surprisingly, however, this residue does not affect hCG or for bLH binding affinity. In fact, the results obtained with bLH and hCG show that several of the divergent residues in the β-sheets of LRR1–9 affect bLH binding affinity, but none of them affect hCG binding affinity. Importantly, our results also emphasize the involvement of residues outside of the β-sheets of the LRRs of the LHR in ligand binding affinity. This finding has to be considered in future models of the interaction of LH/CG with the LHR.
Computed Tomographic Perfusion in the Management of Aneurysmal Subarachnoid Hemorrhage: New Application of an Existent Technique
Authors: Harrigan Mark R. , Magnano Christopher R. , Guterman Lee R. , Hopkins L Nelson
Published: January 2005

OBJECTIVE:

Cerebral blood flow (CBF) alterations are common after aneurysmal subarachnoid hemorrhage (SAH). Treatment of delayed cerebral ischemia in this setting depends on timely and accurate diagnosis. Techniques to measure cerebral blood flow are useful and important. Computed tomographic (CT) perfusion imaging is a technique for the measurement of CBF, cerebral blood volume, and time to peak. It is a fast and inexpensive brain imaging modality that offers promise in the management of patients with SAH.

METHODS:

CT perfusion imaging was performed in 10 patients with aneurysmal SAH when neurological changes raised suspicions of cerebral ischemia. Quantitative values for CBF, cerebral blood volume, and time to peak were obtained in each study. The case history, CT perfusion results, and an analysis of how patient management was influenced are presented for each patient.

RESULTS:

A total of 17 CT perfusion studies were performed. Five studies showed evidence of cerebral ischemia, leading to endovascular treatment of vasospasm. Eight studies excluded cerebral ischemia, and two studies identified cerebral hyperemia, resulting in adjustments in hyperdynamic therapy. CT perfusion was used to help predict a poor prognosis and withhold aggressive intervention in two patients with poor Hunt and Hess grades. Time-to-peak values identified regions of cerebral ischemia more readily than CBF or cerebral blood volume values.

CONCLUSION:

CT perfusion imaging can be used to identify patients with delayed cerebral ischemia after SAH and to guide medical and endovascular therapy. The findings can lead to alterations in patient management.
Differential contributions of Mesp1 and Mesp2 to the epithelialization and rostro-caudal patterning of somites
Authors: Takahashi Yu , Kitajima Satoshi , Inoue Tohru , Kanno Jun , Saga Yumiko
Published: January 2005

Mesp1 and Mesp2 are homologous basic helix-loop-helix (bHLH) transcription factors that are co-expressed in the anterior presomitic mesoderm (PSM) just prior to somite formation. Analysis of possible functional redundancy of Mesp1 and Mesp2 has been prevented by the early developmental arrest of Mesp1/Mesp2 double–null embryos. Here we performed chimera analysis, using either Mesp2-null cells or Mesp1/Mesp2 double–null cells, to clarify (1)possible functional redundancy and the relative contributions of both Mesp1 and Mesp2 to somitogenesis and (2) the level of cell autonomy of Mesp functions for several aspects of somitogenesis. Both Mesp2-null and Mesp1/Mesp2 double–null cells failed to form initial segment borders or to acquire rostral properties, confirming that the contribution of Mesp1 is minor during these events. By contrast, Mesp1/Mesp2 double–null cells contributed to neither epithelial somite nor dermomyotome formation, whereas Mesp2-null cells partially contributed to incomplete somites and the dermomyotome. This indicates that Mesp1 has a significant role in the epithelialization of somitic mesoderm. We found that the roles of the Mesp genes in epithelialization and in the establishment of rostral properties are cell autonomous. However, we also show that epithelial somite formation, with normal rostro-caudal patterning, by wild-type cells was severely disrupted by the presence of Mesp mutant cells, demonstrating non-cell autonomous effects and supporting our previous hypothesis that Mesp2 is responsible for the rostro-caudal patterning process itself in the anterior PSM, via cellular interaction.
Polymodal Sensory Function of theCaenorhabditis elegansOCR-2 Channel Arises from Distinct Intrinsic Determinants within the Protein and Is Selectively Conserved in Mammalian TRPV Proteins
Authors: Sokolchik Irina , Tanabe Takahiro , Baldi Pierre F. , Sze Ji Ying
Published: January 2005

Caenorhabditis elegansOCR-2 (OSM-9 and capsaicin receptor-related) is a TRPV (vanilloid subfamily of transient receptor potential channel) protein that regulates serotonin (5-HT) biosynthesis in chemosensory neurons and also mediates olfactory and osmotic sensation. Here, we identify the molecular basis for the polymodal function of OCR-2 in its native cellular environment. We show that OCR-2 function in 5-HT production and osmotic sensing is governed by its N-terminal region upstream of the ankyrin repeats domain, but the diacetyl sensitivity is mediated by independent mechanisms. Theocr-2(yz5)mutation results in a glycine-to-glutamate substitution (G36E) within the N-terminal region. The G36E substitution causes dramatic downregulation of 5-HT synthesis in the ADF neurons, eliminates osmosensation mediated by the ASH neurons, but does not affect the response to the odorant diacetyl mediated by the AWA neurons. Conversely, wild-type sequence of the N-terminal segment confers osmotic sensitivity and upregulation of 5-HT production to a normally insensitiveC. eleganshomolog, OCR-4, but this chimeric channel does not respond to diacetyl stimuli. Furthermore, expression of either the mouse or human TRPV2 gene under theocr-2promoter can substantially restore 5-HT biosynthesis inocr-2-null mutants but cannot improve the deficits in osmotic or olfactory sensation, suggesting that TRPV2 can substitute for the role of OCR-2 only in serotonergic neurons. Thus, different sensory functions of OCR-2 arise from separable intrinsic determinants, and specific functional properties of TRPV channel proteins may be selectively conserved across phyla.
Softwareagenten: Von den Eigenschaften zur Architektur (Software-Agents: From Properties to Architectures)
Authors: Lockemann Peter C. , Nimis Jens
Published: January 2005

Das moderne Prinzip der Dienstorientierten Architektur scheint ideal auf den Entwurf von Softwareagenten zugeschnitten. Gibt es ein gemeinsames Verständnis für die Eigenschaften von Softwareagenten, so müsste sich nach diesem Prinzip sogar eine Referenzarchitektur finden lassen als eine Art Handlungsanweisung für die Entwicklung konkreter Agenten. Dieser Beitrag schlägt auf der Grundlage allgemein akzeptierter Eigenschaften eine solche Referenzarchitektur vor und illustriert, wie sich bekannte Architekturen dort einpassen lassen.
Mikroprozessor im Hardware-/Software-Codesign (Microprocessor by Hardware-/Software-Codesign)
Authors: Menge Matthias
Published: January 2005

An der TU-Berlin ist die skalare 32-Bit Mikroprozessor-Architektur Nemesis entwickelt und in unterschiedlichen, sich in Komplexität und Geschwindigkeit signifikant unterscheidenden Varianten als IPs (Intellectual Properties) für FPGAs von Xilinx realisiert worden. Dieser Beitrag beschreibt die leistungsfähigste Implementierung Nemesis X, in der durch Verwendung der so genannten Dynamic-Binary-Translation, trotz geringer Komplexität, bis zu drei Instruktionen pro Takt ausgeführt werden.
Volumenvisualisierung auf handelsüblicher Grafik-Hardware (Volume Rendering Techniques for General Purpose Graphics Hardware)
Authors: Rezk Salama Christof
Published: January 2005

Techniken der Volumenvisualisierung werden zur räumlichen Darstellung dreidimensionaler Skalarfelder benötigt, wie sie beispielsweise in der Medizin in Form von tomografischen Daten entstehen. Diese Arbeit beschäftigt sich mit Ansätzen, hochqualitative Bilder solcher Volumendaten in Echtzeit mithilfe handelsüblicher Grafikkarten zu erzeugen.
Research Strategies in the Study of Shamanism and Anomalous Experience
Authors: Krippner Stanley
Published: January 2005

The anomalous experiences of shamans have been reported over the centuries, but only recently have they been subjected to rigorous investigation. Although interviews, reports, and informal observations can produce interesting material, their anomalous nature can only be determined by controlled observations and experimental studies. Examples of each are given and recommendations are made for further research.
The Visionary Experience in North American Shamanism
Authors: Lyon William S.
Published: January 2005

One unique feature found in many of the traditional Native American cultures in North America is that they socially sanction visionary experiences in individuals. How the visionary experience is used in these cultures and, in particular, in shamanism, is discussed. It is suggested that the process of using induction techniques for visionary experiences, in order to acquire shamanic power, may over time have an adverse affect on the shaman's ability.