bluuebunny/crossref_metadata_2025 huggingface dataset:
Endogenous Distress in Ventilated Full-Term Newborns with Acute Respiratory Failure
Authors: Aretz Stefan , Licht Christoph , Roth Bernhard
Published: January 2004

Objective: The main rationale behind the continuous analgesia/sedation currently practiced in the treatment of neonates with severe respiratory failure in intensive care is an attempt at shielding the sick newborn from exogenous stress and pain caused by diagnostic and therapeutic interventions. Until now, however, the factors which influence endogenous, disease-related distress have been largely ignored. Method: We retrospectively studied the daily need for analgesics and sedatives (fentanyl, midazolam, pentobarbital, thiopental) of 40 full-term newborns with severe respiratory failure who had been ventilated for at least 48 h over an observational period of 2–5 days. Dosing of the analgesics and sedatives was based on a neonatal sedation score for ventilated infants. These daily amounts were converted to a normative comparative dose (analgesic/sedative need = ASN) and compared with the oxygenation index (OI) as a measure of the degree of pulmonary insufficiency. Results: Depending on the duration of ventilation, an increasingly close correlation between the ASN and the OI was detected: the index of correlation (r) was detected to be 0.65 on the second day, but increased up to 0.94 after 5 days. The subgroup of patients who had been ventilated for more than 3 days (n = 8) consistently showed a very high correlation, ranging from r = 0.86 to r = 0.94. Conclusion: Our results indicate a direct relationship between severity of pulmonary failure (expressed as OI) and degree of disease-related distress (reflected by ASN). This supports the hypothesis that in full-term neonates under mandatory intensive care for severe respiratory failure, endogenous distress caused by the primary disease itself, in addition to exogenous distress caused by therapeutic and diagnostic interventions, is key factor for the determination of the required amount of analgesic and sedative drugs.
Reduction of Brain and Sense Organs in the Fossil Insular Bovid Myotragus
Authors: Köhler Meike , Moyà-Solà Salvador
Published: January 2004

Our study of the fossil rupicaprine bovid Myotragus [Bate, 1909] from the Mediterranean island Majorca (Spain) provides evidence that this animal underwent significant changes (reduction) in the relative size of brain and sense organs after geographic isolation at the end of the Messinian Salinity Crisis (Miocene-Pliocene boundary, 5.2 Mya). The changes in the central nervous system of Myotragus parallel the pattern reported for domesticated animals, in which decrease in relative brain size is accompanied by a decrease in the relative size of their sense organs. We interpret the important size reduction of brain and sense organs in Myotragus as an adaptive strategy for more efficient energy use under the special environmental conditions of the insular ecosystem, characterized by absence of predation and limitation of trophic resources.
Social Status Interacts with Badge Size and Neuroendocrine Physiology to Influence Sexual Behavior in Male House Sparrows (Passer domesticus)
Authors: Riters Lauren V. , Teague Donald P. , Schroeder Molly B.
Published: January 2004

Reproduction results from a complex interplay among multiple factors including social stimuli, hormones, the brain, and an individual’s physical characteristics. Male house sparrows (Passer domesticus) possess a bib of black feathers, or badge, that is associated with behaviors important for reproduction including courtship behaviors, copulation, and aggression. Such behaviors are controlled by testosterone activity within the central nervous system and are strongly influenced by social status and female behavior. To understand how multiple factors interact to coordinate reproductive activity we explored relationships among social status, badge size, gonad volume, and the volumes of brain regions involved in male courtship and dominance (HVC, robust nucleus of the archistriatum, and the medial preoptic nucleus). A trend toward a U-shaped relationship was observed between dominance status and badge size, with the most dominant and most subordinate males possessing the largest badges. Male vocal expression, copulation, and aggression were positively related to dominance status, but not badge size. In contrast, the volumes of HVC, the medial preoptic nucleus and the gonads related positively to badge size, but not dominance. Females preferentially approached large-badged males regardless of dominance status, but this interest translated into copulation for dominant rather than subordinate males, a finding possibly related to the observation that dominant males vocalized at higher rates than subordinates. Subordinate males that had large badges, attracted female interest, and possessed the neuroendocrine potential to perform courtship behaviors might have been prevented from doing so through social interactions with dominant males within the flock.
Oxytocin and Vasopressin Immunoreactivity within the Forebrain and Limbic-Related Areas in the Mustached Bat, Pteronotus parnellii
Authors: Prasada Rao P.D. , Kanwal Jagmeet S.
Published: January 2004

The nonapeptides, oxytocin and arginine vasopressin, play an important role in mammalian social and reproductive behavior. Using immunocytochemical procedures, we identified oxytocin-immunoreactive neurons in the frontal and auditory cortices, limbic areas such as the medial septal nucleus, horizontal limb of the diagonal band and the amygdala. Only arginine vasopressin neurons were present in the bed nucleus of the stria terminalis. In limbic-related areas, the hypothalamic paraventricular and supraoptic nuclei and the nucleus centralis contained both oxytocin and arginine vasopressin neurons. The medial preoptic area showed a positive reaction for several arginine vasopressin fibers, but not oxytocin fibers, except in one female bat sacrificed during the breeding season. Arginine vasopressin fibers were observed in another limbic-related area, the periaqueductal gray. Furthermore, oxytocin was predominantly localized within sensory (e.g., auditory) and frontal cortex and limbic areas, whereas arginine vasopressin was restricted largely to known audiovocal regions of the periaqueductal gray. Classical neurosecretory nuclei in the hypothalamus contain both peptides. Oxytocin-immunoreactive neurons were also found in other structures such as the olfactory bulb, olfactory tubercle, primary and secondary motor cortex, fronto-parietal cortex, piriform cortex and the nucleus of the internal capsule. Both oxytocin and arginine vasopressin immunoreactivity was present in the suprachiasmatic nucleus, median eminence, neural lobe of the hypophysis and the pineal gland. Together with previous studies, the presence of these peptides within auditory areas of the cortex (sensory and frontal), and limbic as well as limbic-related regions provides anatomical evidence supporting their proposed role in social vocal behaviors and probably in auditory processing.
Bigger Brains or Bigger Nuclei? Regulating the Size of Auditory Structures in Birds
Authors: Kubke M. Fabiana , Massoglia Dino P. , Carr Catherine E.
Published: January 2004

Increases in the size of the neuronal structures that mediate specific behaviors are believed to be related to enhanced computational performance. It is not clear, however, what developmental and evolutionary mechanisms mediate these changes, nor whether an increase in the size of a given neuronal population is a general mechanism to achieve enhanced computational ability. We addressed the issue of size by analyzing the variation in the relative number of cells of auditory structures in auditory specialists and generalists. We show that bird species with different auditory specializations exhibit variation in the relative size of their hindbrain auditory nuclei. In the barn owl, an auditory specialist, the hindbrain auditory nuclei involved in the computation of sound location show hyperplasia. This hyperplasia was also found in songbirds, but not in non-auditory specialists. The hyperplasia of auditory nuclei was also not seen in birds with large body weight suggesting that the total number of cells is selected for in auditory specialists. In barn owls, differences observed in the relative size of the auditory nuclei might be attributed to modifications in neurogenesis and cell death. Thus, hyperplasia of circuits used for auditory computation accompanies auditory specialization in different orders of birds.
Efficacy of Prednisolone and Mizoribine Therapy for Diffuse IgA Nephropathy
Authors: Kawasaki Yukihiko , Suzuki Junzo , Sakai Nobuko , Etoh Shigehiko , Murai Hiromitch , Nozawa Ruriko , Suzuki Hitoshi
Published: January 2004

Objective: There have been only a few studies concerning oral prednisolone and mizoribine therapy for diffuse IgA nephritis (IgAN). We evaluated the efficacy of prednisolone and mizoribine therapy for diffuse IgAN. Methods: We enrolled 34 patients who had been diagnosed as having diffuse IgAN with severe proteinuria during the period from 1992 to 1999. Following diagnostic renal biopsy, the patients were treated with prednisolone, mizoribine, warfarin and dilazep dihydrochloride. The clinical features, laboratory data and pathological findings between pre- and post-therapy were investigated. Results: The mean urinary protein excretion after 6 months of treatment had decreased significantly compared to pre-therapy. The incidence of hematuria in post-therapy was lower than that of pre-therapy. The grading index decreased significantly from 4.8 ± 2.1 at the first biopsy to 2.3 ± 1.7 at the second biopsy (p < 0.001) and the staging index decreased significantly from 4.1 ± 1.9 at the first biopsy to 2.7 ± 2.4 at the second biopsy (p < 0.05). Macrophage infiltration and α-smooth muscle actin-positive cells in the glomerulus and interstitial region decreased significantly in post-therapy compared with pre-therapy. At the most recent follow-up, none of the 34 patients had renal insufficiency. Conclusions: Our study suggested that prednisolone and mizoribine therapy is effective for those patients with the risk of progression of IgAN.
Oxidative Stress – a Link between Endothelial Injury, Coagulation Activation, and Atherosclerosis in Haemodialysis Patients
Authors: Pawlak Krystyna , Naumnik Beata , Brzósko Szymon , Pawlak Dariusz , Myśliwiec Michał
Published: January 2004

Background/Aim: Recently emerging evidence suggests that oxidative stress (SOX) may participate in atherogenesis. The aim of the present study was to establish whether enhanced SOX, involving endothelial injury, activation of coagulation, and inflammatory reaction, could be implicated in atherosclerotic diseases in haemodialysis (HD) patients. Methods: Markers of SOX, endothelial injury, coagulation, and cytokines, were measured in the plasma of HD patients with and without cardiovascular disease (CVD), and of healthy controls by ELISA methods. Remodeling of the carotid arteries was assessed by measuring the intima-media thickness (IMT) as a surrogate of atherosclerotic disease in all groups. Results: Markers of SOX, endothelial injury, and extrinsic coagulation pathway activation and IMT values were significantly elevated in HD patients, especially in those with CVD when compared with the control group. The von Willebrand factor antigen (vWF:Ag) levels were more increased in the patients with CVD than in those without. Furthermore, the plasma levels of tumour necrosis factor alpha, monocyte chemo-attractant protein 1, and macrophage inflammatory protein 1 beta were significantly higher only in the HD group with CVD when compared with the controls. The IMT was strongly and directly correlated with Cu/Zn superoxide dismutase. Both IMT and Cu/Zn superoxide dismutase were positively correlated with age, thrombomodulin, vWF:Ag, tissue factor, tissue factor pathway inhibitor, prothrombin fragment F1 + 2, monocte chemo-attractant protein 1, macrophage inflammatory protein 1 beta, and tumour necrosis factor alpha levels. Multivariate analysis identified vWF:Ag as the only independent variable significantly associated with an increased IMT. Conclusions: The present study suggests that enhanced SOX, involved pro-atherogenic cytokine and chemokines levels, endothelial injury, and coagulation activation may constitute a pathway for accelerated atherosclerosis in HD patients. The significant, independent association between IMT and vWF:Ag should be assessed in future studies to determine whether vWF:Ag elevation is causative or a by-product of the increased IMT.
Two-Photon Microscopy for Imaging of the (Atherosclerotic) Vascular Wall: A Proof of Concept Study
Authors: van Zandvoort Marc , Engels Wim , Douma Kim , Beckers Linda , oude Egbrink Mirjam , Daemen Mat , Slaaf Dick W.
Published: January 2004

Background: Understanding atherogenesis will benefit significantly from simultaneous imaging, both ex vivo and in vivo, of structural and functional information at the (sub)cellular level within intact arteries. Due to limited penetration depth and loss of resolution with depth, intravital and confocal fluorescence microscopy are not suitable to study (sub)cellular details in arteries with wall thicknesses above 50 µm. Methods: Using two-photon laser scanning microscopy (TPLSM), which combines 3D resolution and large penetration depth, we imaged mouse carotid arteries. Results: In thin slices, (sub)cellular structures identified using histochemical techniques could also be identified using TPLSM. Ex vivo, structural experiments on intact atherosclerotic arteries of Apo-E–/– mice demonstrated that in contrast to confocal or wide-field microscopy, TPLSM can be used to visualize (sub) cellular structural details of atherosclerotic plaques. In vivo, pilot experiments were carried out on healthy arteries of wild-type C57BL6 and atherosclerotic arteries of Apo-E–/– mice. As an example of functional measurements, we visualized fluorescently labeled leukocytes in vivo in the lumen. Additionally, detailed morphological information of vessel wall and atherosclerotic plaque was obtained after topical staining. Conclusions: Thus, TPLSM potentially allows combined functional and structural studies and can therefore be eminently suitable for investigating structure-function relationships at the cellular level in atherogenesis in the mouse.
Role of Reactive Oxygen Species-Sensitive Extracellular Signal-Regulated Kinase Pathway in Angiotensin II-Induced Endothelin-1 Gene Expression in Vascular Endothelial Cells
Authors: Hsu Yung-Ho , Chen Jin-Jer , Chang Nen-Chung , Chen Cheng-Hsien , Liu Ju-Chi , Chen Tso-Hsiao , Jeng Cherng-Jye , Chao Hung-Hsing , Cheng Tzu-Hurng
Published: January 2004

Background: Circulating angiotensin II (Ang II) increases vascular endothelin-1 (ET-1) tissue levels, which in turn mediate a major part of Ang II-stimulated vascular growth and hypertension in vivo. Ang II also stimulates the generation of reactive oxygen species (ROS) within vascular endothelial cells. However, whether ROS are involved in Ang II-induced ET-1 gene expression, and the related intracellular mechanisms occurring within vascular endothelial cells remain unclear. Methods: Cultured endothelial cells were stimulated with Ang II, and the thus elicited ET-1 gene expression was examined by Northern blotting and a promoter activity assay. Antioxidant pretreatment of endothelial cells was performed prior to Ang II-induced extracellular signal-regulated kinase (ERK) phosphorylation in order to elucidate the redox-sensitive pathway for ET-1 gene expression. Results: The ET-1 gene was induced with Ang II, which was inhibited with Ang II type 1 receptor antagonist (irbesartan). Ang II-enhanced intracellular ROS levels were inhibited by irbesartan and several antioxidants, and antioxidants also suppressed Ang II-induced ET-1 gene expression. Further, Ang II-activated ERK phosphorylation was also significantly inhibited by certain antioxidants. An ERK inhibitor, U0126, inhibited Ang II-induced ET-1 expression completely. Cotransfection of the dominant negative mutant of Ras, Raf and MEK1 (ERK kinase) attenuated the Ang II-enhanced ET-1 promoter activity, suggesting that the Ras/Raf/ERK pathway is required for Ang II-induced ET-1 gene expression. Ang II-induced activator protein-1 (AP-1) reporter activities were inhibited by antioxidants. Moreover, mutational analysis of the ET-1 gene promoter showed that the AP-1 binding site was an important cis element in Ang II-induced ET-1 gene expression. Conclusions: Our data suggest that ROS are involved in Ang II-induced ET-1 gene expression within endothelial cells. The redox-sensitive ERK-mediated AP-1 transcriptional pathway plays an important role in Ang II-induced ET-1 gene expression.
Moyamoya Angiopathy with Dolichoectatic Internal Carotid Arteries, Patent Ductus arteriosus and Pupillary Dysfunction: A New Genetic Syndrome?
Authors: Khan Nadia , Schinzel Albert , Shuknecht Bernhard , Baumann Fabian , Østergaard John R. , Yonekawa Yasuhiro
Published: January 2004

We report on 2 children with moyamoya angiopathy and bilateral dolichoectatic internal carotid arteries in combination with iris hypoplasia with bilateral fixed dilated pupils and a history of patent ductus arteriosus. Both were symptomatic with moyamoya angiopathy and underwent bilateral extracranial-intracranial (EC-IC) bypass operations for cerebral revascularization. This is the first report on moyamoya angiopathy and bilateral dolichoectatic internal carotid arteries with simultaneous occurrence of ocular and cardiovascular malformations. There have been descriptions of cerebral vascular abnormalities in combination with either congenital heart disease or ocular abnormalities but not with both presenting together. The combination of these separate congenital developmental defects may not be purely coincidental: we propose that the 2 probands are affected with a not yet recognized clinical syndrome of probably genetic etiology.
Efficacy of Fluvoxamine as a Treatment for Behavioral Symptoms in Frontotemporal Lobar Degeneration Patients
Authors: Ikeda Manabu , Shigenobu Kazue , Fukuhara Ryuji , Hokoishi Kazuhiko , Maki Naruhiko , Nebu Akihiko , Komori Kenjiro , Tanabe Hirotaka
Published: January 2004

Patients with frontotemporal lobar degeneration (FTLD) present a profound personality change, social misconduct, overeating, and stereotyped behavior. We examined the hypothesis that many of the behavioral symptoms of FTLD will respond to selective serotonin reuptake inhibitors (SSRIs). Sixteen FTLD patients were treated with an SSRI (fluvoxamine maleate) in an open 12-week trial. Treatment responses for stereotyped behavior and other neurobehavioral symptoms were evaluated by the Stereotypy Rating Inventory and the Neuropsychiatric Inventory. The behavioral symptoms, especially stereotyped behaviors of FTLD, significantly improved after treatment. Randomized, placebo- and other SSRI-controlled trials may improve available treatments.
Regional Analysis of Differently Phosphorylated Tau Proteins in Brains from Patients with Alzheimer’s Disease
Authors: Nakano Hiroyuki , Kobayashi Katsuji , Sugimori Kaoru , Shimazaki Masao , Miyazu Kenji , Hayashi Masahiro , Furuta Hisakazu
Published: January 2004

Neurofibrillary tangles (NFT) in Alzheimer’s disease (AD) are composed of abnormally phosphorylated tau proteins. Many phosphorylation sites have been reported in the AD brain, and NFT distribution was now roughly classified into 3 stages by Braak stage; this classification is based on pathological studies using the specific silver impregnation technique. The aim of our study was to examine the regional distribution of differently phosphorylated tau proteins with 5 site-specific monoclonal antibodies against the tau proteins, AT8, AT180, HT7, Tau2 and Tau5. We then compared our findings with those obtained from silver-stained NFT in an attempt to clarify the relationship between abnormal phosphorylation sites of the tau protein and NFT development. AT180 and AT8 labeled the highest and Tau2 the lowest density of NFT in any regions, while Tau5 and HT7 showed inconsistent distribution. In the limbic cortex, cornu ammonis, entorhinal cortex and cingulate cortex, silver-stained NFT density significantly correlated with density of NFT labeled with the 5 anti-tau antibodies, but cerebral isocortices showed heterogenous patterns of tau-positive NFT. Quantification of tau-positive regional NFT density showed that the AD-associated phosphorylation process progresses from the C-terminal to the N-terminal of the amino acid sequence, and correlation of Gallyas-stained NFT density with tau-labeled NFT density was more significant in the limbic cortices than the cerebral isocortices, which implies that stereotypical phosphorylation occurs in the limbic structures.
Apolipoprotein E Gene Polymorphism in Indian Patients with Alzheimer’s Disease and Vascular Dementia
Authors: Luthra Kalpana , Tripathi Manjari , Grover Rahul , Dwivedi Manjari , Kumar Amit , Dey A.B.
Published: January 2004

The association of apolipoprotein E (ApoE) gene polymorphism with Alzheimer’s disease (AD) has been reported in several populations including one from a rural community in North India. However, the association of ApoE polymorphism with vascular dementia (VaD) is yet to be established in this population. In a case-control study involving 54 cases of dementia (29 AD and 25 VaD) and 76 age-matched healthy controls, the frequency of Ε4 allele was significantly higher among cases of AD and VaD compared with controls (p < 0.001). The Ε3Ε3 (p < 0.05) and Ε2Ε3 (p < 0.001) genotypes were found to be protective. The odds of developing AD or VaD were 4.4 and 3.7 times higher, respectively, in the presence of even a single Ε4 allele. Our results suggest that the increased risk of developing AD or VaD is similar among Asian Indians with ApoE Ε4 compared with the Caucasian population.
The Fas Promoter Polymorphism at Position –670 Is Not Associated with Late-Onset Sporadic Alzheimer’s Disease
Authors: Rosenmann Hanna , Meiner Zeev , Kahana Esther , Aladjem Zoja , Friedman Gideon , Ben-Yehuda Arie , Grenader Tal , Wertman Eli , Abramsky Oded
Published: January 2004

The Fas antigen is a cell surface receptor-mediating cell apoptosis. Recent studies have demonstrated that Fas-associated apoptosis is involved in the pathogenesis of Alzheimer’s disease (AD). Moreover, the Fas gene is located on chromosome 10q24.1, a region of linkage to late-onset AD (LOAD). These two criteria, pathobiological and positional, make the Fas antigen an interesting candidate for an association with AD. We performed a case-control association study between the common A/G polymorphism at position –670 in the Fas gene (TNFSRF6) promoter and sporadic AD in Jews, investigating whether this locus acts as a risk factor or whether it has a modifying effect. An association has recently been detected by Feuk et al. in the Scottish population between this locus and the risk of early-onset AD (EOAD), but not of LOAD. In agreement with Feuk et al., we found no association between this locus and the risk of LOAD (n = 86). However, in our small sample of patients with EOAD (n = 19), no association was found either. No interactive effect was found between the Fas promoter polymorphism at position –670 and the known risk factor of LOAD, apolipoprotein E Ε4, and no association was detected with disease progression. These findings show no evidence for an association between the Fas promoter polymorphism at position –670 and AD in our population.
The Regulatory Region Polymorphisms of the MTHFR Gene Are Not Associated with Alzheimer’s Disease
Authors: Wakutani Yosuke , Kowa Hisanori , Kusumi Masayoshi , Nakaso Kazuhiro , Isoe-Wada Kenji , Yano Hidetaka , Urakami Katsuya , Takeshima Takao , Nakashima Kenji
Published: January 2004

Recent epidemiological studies have emphasized the impact of elevated blood homocysteine levels on the pathogenesis of Alzheimer’s disease (AD). In spite of a significant impact of a MTHFR C677T polymorphism on the blood homocysteine levels, the association between the C677T polymorphism and AD remains controversial. Therefore, other unidentified genetic factor(s) that regulate blood homocysteine levels may exist. Here, we have analyzed the 5′-upstream region of the MTHFR gene and examined AD patients (n = 223) and nondemented individuals (n = 323) for polymorphisms in the 5′-upstream region of the MTHFR gene. We identified two polymorphisms (–713G/A and –393C/A, upstream of the start codon). We found no significant relationship between AD and the 5′-upstream region polymorphisms of the MTHFR gene. Thus, our study does not reinforce the hypothesis of an independent involvement of the MTHFR gene upstream region polymorphisms in AD risk.
Results of Quinacrine Administration to Patients with Creutzfeldt-Jakob Disease
Authors: Nakajima Masashi , Yamada Tatsuo , Kusuhara Tomohiko , Furukawa Hisako , Takahashi Mitsuo , Yamauchi Atsushi , Kataoka Yasufumi
Published: January 2004

Several chemicals inhibit the accumulation of abnormal prion proteins in vitro. We administered one, the antimalarial agent quinacrine, to three patients with sporadic Creutzfeldt-Jakob disease (CJD) and to one with iatrogenic CJD. Quinacrine at 300 mg/day was given enterally for 3 months. Within 2 weeks of administration, the arousal level of the patient with akinetic mutism improved. The other 3 patients, insensible before treatment, had integrative responses such as eye contact or voluntary movement in response to verbal and/or visual stimuli restored. Clinical improvement was transient, lasting 1–2 months during treatment. Quinacrine was well tolerated, except for liver dysfunction and yellowish pigmentation. Although its antiprion activity in the human brain has yet to be proved, these modest effects of quinacrine suggest the possibility of using chemical intervention against prion diseases.
Association of the Neprilysin Gene with Susceptibility to Late-Onset Alzheimer’s Disease
Authors: Sakai Ayumu , Ujike Hiroshi , Nakata Kenji , Takehisa Yasushi , Imamura Takaki , Uchida Naohiko , Kanzaki Akihiro , Yamamoto Mitsutoshi , Fujisawa Yoshikatsu , Okumura Kazuya , Kuroda Shigetoshi
Published: January 2004

Neprilysin (NEP), also known as neutral endopeptidase, enkephalinase, CD 10, and common acute lymphoblastic leukemia antigen, is a 97-kD protein. NEP can degrade amyloid β peptides, and its mRNA and protein levels are known to be reduced in the brains of patients with Alzheimer’s disease (AD), making the NEP gene a substantial candidate for an AD risk factor. We examined the genetic association of three NEP polymorphisms, a GT-repeat polymorphism and two single nucleotide polymorphisms (SNPs, –1075A>G and –1284G>C) in its promoter region, with AD in a Japanese case-control sample (240 patients and 163 controls). The GT-repeat polymorphism, but not the SNPs, was significantly associated with late-onset AD (p = 0.0007). Our findings suggest that the GT-repeat polymorphism in the promoter region of the NEP gene or some other unknown polymorphisms, which are in a linkage disequilibrium, confer a susceptibility to late-onset AD.
An Interleukin-6 Promoter Variant Is Not Associated with an Increased Risk for Alzheimer’s Disease
Authors: Depboylu Candan , Lohmüller Frank , Gocke Petra , Du Yansheng , Zimmer Reinhilde , Gasser Thomas , Klockgether Thomas , Dodel Richard C.
Published: January 2004

Recent studies have implicated interleukin-6 (IL-6) in the pathogenesis of Alzheimer’s disease (AD). Neuro-inflammatory processes surrounding the amyloid plaques contribute to the progression of AD-related neurodegeneration. IL-6 is a multifunctional inflammatory cytokine which possibly acts as a mediator in the local immune response in the brain of AD patients. In this study we investigated whether the risk of developing AD is altered in carriers of the C allele of a G/C polymorphism at position –174. 113 AD patients and 108 age- and gender-matched nondemented control subjects were analysed. Genotyping of IL-6 was performed using standard PCR and restriction fragment length polymorphism methods. The results were adjusted for age, gender and apolipoprotein E Ε4 status. There was no evidence for an association between the polymorphism and the risk of developing AD. No evidence of an earlier age at onset for carriers of the C allele was evaluated. We conclude that IL-6 (–174) polymorphism does not influence the risk of developing AD in our cohort.
Getting Lost: Directed Attention and Executive Functions in Early Alzheimer’s Disease Patients
Authors: Chiu Yi-Chen , Algase Donna , Whall Ann , Liang Jersey , Liu Hsiu-Chih , Lin Ker-Neng , Wang Pei-Ning
Published: January 2004

This study explores the link between directed attention (DA) and getting lost behavior (GLB) in early Alzheimer’s disease (AD) using a cross-sectional design with 3 groups. Based on their dementia levels, 116 community-dwelling participants were recruited from a teaching hospital in Taiwan and classified as the non-demented control, questionably demented, and mild AD groups. Statistical analyses include Pearson correlations, one-way ANOVA, and multiple regressions. Attentional impairments, consisting of distractibility, impulsivity, and executive function problems, significantly predict GLB in familiar and unfamiliar environments. Irritability and executive function problems are associated with mental difficulties in choosing a turn, whereas the use of way-finding strategies reduces GLB. Future interventions may include: (a) mental hygiene of aging; (b) programs targeted at improving attentional function and effective way-finding, and (c) inclusion of DA tests in a routine clinical neuropsychological examination for early detection and accurate diagnosis of dementia.
Awareness of Deficits in Mild Cognitive Impairment and Alzheimer’s Disease: Do MCI Patients Have Impaired Insight?
Authors: Vogel Asmus , Stokholm Jette , Gade Anders , Andersen Birgitte Bo , Hejl Anne-Mette , Waldemar Gunhild
Published: January 2004

In this study we investigated impaired awareness of cognitive deficits in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Very few studies have addressed this topic, and methodological inconsistencies make the comparison of previous studies difficult. From a prospective research program 36 consecutive patients with mild AD (MMSE above 19), 30 with amnesic MCI and 33 matched controls were examined. Using three methods for awareness assessment we found no significant differences in the level of awareness between MCI and AD. Both groups had impaired awareness and significant heterogeneity in the clinical presentation of awareness. The results demonstrate that subjective memory problems should not be a mandatory prerequisite in suspected dementia or MCI, which makes reports from informants together with thorough clinical interview and observation central when assessing suspected dementia disorders.
Semantic Knowledge of Famous People in Mild Cognitive Impairment and Progression to Alzheimer’s Disease
Authors: Estévez-González Armando , García-Sánchez Carmen , Boltes Anunciación , Otermín Pilar , Pascual-Sedano Berta , Gironell Alex , Kulisevsky Jaime
Published: January 2004

Patients with dementia of Alzheimer’s type (DAT) show severe impairment in recognizing famous people. The aim of the current study was to investigate if this well-known memory impairment of famous faces is already present in the preclinical phase of DAT and if the famous faces test can help to differentiate patients with mild cognitive impairment (MCI) who progress to dementia and those who do not. We compared baseline performance in a task of famous face identification in a sample of 116 patients with subjective memory complaints classified in three groups: 17 participants with no evidence of cognitive impairment; 26 patients with MCI who had not developed dementia, and 27 patients with MCI who had developed probable DAT 2 years later. The remaining patients were excluded because they abandoned or did not meet the applied restrictive criteria for DAT, MCI or control. MCI patients who were diagnosed 2 years later with DAT performed significantly worse in the preclinical phase than MCI and control participants (p < 0.004). Patients with MCI but not DAT obtained intermediate results between control subjects and MCI patients who develop Alzheimer’s disease. A neuropsychological task of semantic knowledge of famous people may be useful in the early diagnosis of Alzheimer’s disease.
CSF Lactate Dehydrogenase Activity in Patients with Creutzfeldt-Jakob Disease Exceeds That in Other Dementias
Authors: Schmidt H. , Otto M. , Niedmann P. , Cepek L. , Schröter A. , Kretzschmar H.A. , Poser S.
Published: January 2004

The diagnosis of Creutzfeldt-Jakob disease (CJD) is still made by exclusion of other dementias. We now evaluated lactate dehydrogenase (LDH) in the cerebrospinal fluid (CSF) as a possible additional diagnostic tool. CSF LDH levels of patients with CJD (n = 26) were compared with those in other dementias (n = 28). LDH isoenzymes were determined in a subset (n = 9). Total LDH and isoenzyme LDH-1 were significantly higher, whereas the fractions of LDH-2 and LDH-3 were significantly lower in CJD patients. We conclude that in addition to established CSF parameters, LDH and its isoenzymes might serve as a further help to discriminate between CJD and other dementias.
Transcobalamin Polymorphism and Serum Holo-Transcobalamin in Relation to Alzheimer’s Disease
Authors: McCaddon Andrew , Blennow Kaj , Hudson Peter , Hughes Alan , Barber Joan , Gray Rob , Davies Gareth , Williams John H.H. , Duguid Jennifer , Lloyd Alwyn , Tandy Steve , Everall Marge , Cattell Howard , McCaddon Anne , Ellis Dick , Palmėr Mona , Bogdanovic Nenad , Gottfries Carl-Gerhard , Zetterberg Henrik , Rymo Lars , Regland Björn
Published: January 2004

Isoforms of the vitamin B12 carrier protein transcobalamin (TC) might influence its cellular availability and contribute to the association between disrupted single-carbon metabolism and Alzheimer’s disease (AD). We therefore investigated the relationships between the TC 776C>G (Pro259Arg) genetic polymorphism, total serum cobalamin and holo-TC levels, and disease onset in 70 patients with clinically diagnosed AD and 74 healthy elderly controls. TC 776C>G polymorphism was also determined for 94 histopathologically confirmed AD patients and 107 controls. Serum holo-TC levels were significantly higher in TC 776C homozygotes (p = 0.04). Kaplan-Meier survival functions differed between homozygous genotypes (Cox’s F-Test F(42, 46) = 2.1; p = 0.008) and between 776C homozygotes and heterozygotes (Cox’s F test F(46, 108) = 1.7; p = 0.02). Proportionately fewer TC 776C homozygotes appear to develop AD at any given age, but this will require confirmation in a longitudinal study.
The Fuzzy Frontier between Subjective Memory Complaints and Early Dementia
Authors: Rösler A. , Gönnenwein C. , Müller N. , Sterzer P. , Kleinschmidt A. , Frölich L.
Published: January 2004

Background: Mild cognitive decline is frequent in the elderly population. Whether it is related to normal aging or an early phase of evolving dementia is difficult to ascertain with confidence, and accordingly there is a lack of consensus guidelines for diagnosis and therapy in such patients. We assessed the variability with which memory clinics deal with this problem in everyday practice. Methods: We sent three fictitious case histories to all 85 German memory clinics that contained the results of clinical examination and neuropsychological test scores and asked for diagnosis and patient management. Patient 1 presented with complaints of mental decline but normal neuropsychological and neurological evaluation and normal daily living activities. Patient 2 came in as a control subject for a study and had impaired test scores but preserved daily living activities, and patient 3 was brought in by relatives with slight impairment of daily living activities and decline in some neuropsychological test scores but relatively spared memory scores. Results: Most of the 51 respondents agreed in recommending further neuropsychological testing, a basic laboratory work-up, brain imaging, and a re-examination after 3–6 months. Yet, there was a high variability in the diagnostic terms used, in the additional diagnostic procedures proposed, and in the recommendations concerning therapeutic intervention and driving. Conclusions: The results reveal a need of practice guidelines for the use of diagnostic terms, therapeutic interventions and driving recommendations in patients between subjective memory complaints and early dementia.
Bayesian Computation in Recurrent Neural Circuits
Authors: Rao Rajesh P. N.
Published: January 2004

A large number of human psychophysical results have been successfully explained in recent years using Bayesian models. However, the neural implementation of such models remains largely unclear. In this article, we show that a network architecture commonly used to model the cerebral cortex can implement Bayesian inference for an arbitrary hidden Markov model. We illustrate the approach using an orientation discrimination task and a visual motion detection task. In the case of orientation discrimination, we show that the model network can infer the posterior distribution over orientations and correctly estimate stimulus orientation in the presence of significant noise. In the case of motion detection, we show that the resulting model network exhibits direction selectivity and correctly computes the posterior probabilities over motion direction and position. When used to solve the well-known random dots motion discrimination task, the model generates responses that mimic the activities of evidence-accumulating neurons in cortical areas LIP and FEF. The framework we introduce posits a new interpretation of cortical activities in terms of log posterior probabilities of stimuli occurring in the natural world.
Probability of Stimulus Detection in a Model Population of Rapidly Adapting Fibers
Authors: Güçlü Burak , Bolanowski Stanley J.
Published: January 2004

The goal of this study is to establish a link between somatosensory physiology and psychophysics at the probabilistic level. The model for a population of monkey rapidly adapting (RA) mechanoreceptive fibers by Güçlü and Bolanowski (2002) was used to study the probability of stimulus detection when a 40 Hz sinusoidal stimulation is applied with a constant contactor size (2 mm radius) on the terminal phalanx. In the model, the detection was assumed to be mediated by one or more active fibers. Two hypothetical receptive field organizations (uniformly random and gaussian) with varying average innervation densities were considered. At a given stimulus-contactor location, changing the stimulus amplitude generates sigmoid probability-of-detection curves for both receptive field organizations. The psychophysical results superimposed on these probability curves suggest that 5 to 10 active fibers may be required for detection. The effects of the contactor location on the probability of detection reflect the pattern of innervation in the model. However, the psychophysical data do not match with the predictions from the populations with uniform or gaussian distributed receptive field centers. This result may be due to some unknown mechanical factors along the terminal phalanx, or simply because a different receptive field organization is present. It has been reported that human observers can detect one single spike in an RA fiber. By considering the probability of stimulus detection across subjects and RA populations, this article proves that more than one active fiber is indeed required for detection.
Orthogonality of Decision Boundaries in Complex-Valued Neural Networks
Authors: Nitta Tohru
Published: January 2004

This letter presents some results of an analysis on the decision boundaries of complex-valued neural networks whose weights, threshold values, input and output signals are all complex numbers. The main results may be summarized as follows. (1) A decision boundary of a single complex-valued neuron consists of two hypersurfaces that intersect orthogonally, and divides a decision region into four equal sections. The XOR problem and the detection of symmetry problem that cannot be solved with two-layered real-valued neural networks, can be solved by two-layered complex-valued neural networks with the orthogonal decision boundaries, which reveals a potent computational power of complex-valued neural nets. Furthermore, the fading equalization problem can be successfully solved by the two-layered complex-valued neural network with the highest generalization ability. (2) A decision boundary of a three-layered complex-valued neural network has the orthogonal property as a basic structure, and its two hypersurfaces approach orthogonality as all the net inputs to each hidden neuron grow. In particular, most of the decision boundaries in the three-layered complex-valued neural network inetersect orthogonally when the network is trained using Complex-BP algorithm. As a result, the orthogonality of the decision boundaries improves its generalization ability. (3) The average of the learning speed of the Complex-BP is several times faster than that of the Real-BP. The standard deviation of the learning speed of the Complex-BP is smaller than that of the Real-BP. It seems that the complex-valued neural network and the related algorithm are natural for learning complex-valued patterns for the above reasons.
On the Asymptotic Distribution of the Least-Squares Estimators in Unidentifiable Models
Authors: Hayasaka Taichi , Kitahara Masashi , Usui Shiro
Published: January 2004

In order to analyze the stochastic property of multilayered perceptrons or other learning machines, we deal with simpler models and derive the asymptotic distribution of the least-squares estimators of their parameters. In the case where a model is unidentified, we show different results from traditional linear models: the well-known property of asymptotic normality never holds for the estimates of redundant parameters.
Asymptotic Properties of the Fisher Kernel
Authors: Tsuda Koji , Akaho Shotaro , Kawanabe Motoaki , Müller Klaus-Robert
Published: January 2004

This letter analyzes the Fisher kernel from a statistical point of view. The Fisher kernel is a particularly interesting method for constructing a model of the posterior probability that makes intelligent use of unlabeled data (i.e., of the underlying data density). It is important to analyze and ultimately understand the statistical properties of the Fisher kernel. To this end, we first establish sufficient conditions that the constructed posterior model is realizable (i.e., it contains the true distribution). Realizability immediately leads to consistency results. Subsequently, we focus on an asymptotic analysis of the generalization error, which elucidates the learning curves of the Fisher kernel and how unlabeled data contribute to learning. We also point out that the squared or log loss is theoretically preferable-because both yield consistent estimators-to other losses such as the exponential loss, when a linear classifier is used together with the Fisher kernel. Therefore, this letter underlines that the Fisher kernel should be viewed not as a heuristics but as a powerful statistical tool with well-controlled statistical properties.
Adaptive Hybrid Learning for Neural Networks
Authors: Smithies Rob , Salhi Said , Queen Nat
Published: January 2004

A robust locally adaptive learning algorithm is developed via two enhancements of the Resilient Propagation (RPROP) method. Remaining drawbacks of the gradient-based approach are addressed by hybridization with gradient-independent Local Search. Finally, a global optimization method based on recursion of the hybrid is constructed, making use of tabu neighborhoods to accelerate the search for minima through diver-sification. Enhanced RPROP is shown to be faster and more accurate than the standard RPROP in solving classification tasks based on natural data sets taken from the UCI repository of machine learning databases. Furthermore, the use of Local Search is shown to improve Enhanced RPROP by solving the same classification tasks as part of the global optimization method.
Divergence Function, Duality, and Convex Analysis
Authors: Zhang Jun
Published: January 2004

From a smooth, strictly convex function Φ: Rn → R, a parametric family of divergence function DΦ(α) may be introduced:

[Formula: see text]

for x, y, ε int dom(Φ) and for α ε R, with DΦ(±1 defined through taking the limit of α. Each member is shown to induce an α-independent Riemannian metric, as well as a pair of dual α-connections, which are generally nonflat, except for α = ±1. In the latter case, D(±1)Φ reduces to the (nonparametric) Bregman divergence, which is representable using and its convex conjugate Φ * and becomes the canonical divergence for dually flat spaces (Amari, 1982, 1985; Amari & Nagaoka, 2000). This formulation based on convex analysis naturally extends the information-geometric interpretation of divergence functions (Eguchi, 1983) to allow the distinction between two different kinds of duality: referential duality (α -α) and representational duality (Φ  Φ *). When applied to (not necessarily normalized) probability densities, the concept of conjugated representations of densities is introduced, so that ± α-connections defined on probability densities embody both referential and representational duality and are hence themselves bidual. When restricted to a finite-dimensional affine submanifold, the natural parameters of a certain representation of densities and the expectation parameters under its conjugate representation form biorthogonal coordinates. The alpha representation (indexed by β now, β ε [−1, 1]) is shown to be the only measure-invariant representation. The resulting two-parameter family of divergence functionals D(α, β), (α, β) ε [−1, 1] × [-1, 1] induces identical Fisher information but bidual alpha-connection pairs; it reduces in form to Amari's alpha-divergence family when α =±1 or when β = 1, but to the family of Jensen difference (Rao, 1987) when β = 1.
HUMANISM, RACISM AND SPECIESISM
Authors: Brennan Andrew
Published: January 2004

The advance of biological sciences in the last two hundred years seems to have narrowed the distance between humans and animals, and scientists themselves are active in promoting the welfare of experimental animals. Does this mean that continued use of animals in science is inconsistent and morally condemnable as "speciesism"? The paper argues that philosophers' accounts of "speciesism" and the assimilation of "speciesism" to racism by Peter Singer and others are not well founded. Racism is a complex phenomenon, and there is no clear analogy to be drawn between it and the supposed prejudice of "speciesism". The humanist tradition established in the Renaissance can be a source for an ethic of care for animals, and regarding humanism simply as a bias or prejudice akin to "speciesism" (in the sense deployed by Singer) is misleading and simplistic.
ANIMAL RIGHTS AND THEORIES OF ORIGINS: A PLEA FOR UNITY
Authors: Thornhill Richard , Morris Michael
Published: January 2004

A useful philosophical case against vivisection influential with the general public rests on the following three premises: (1) animals have interests as conscious beings; (2) it is unethical to cause pain and suffering to conscious beings for trivial reasons; and (3) animal models cannot be extrapolated to human beings, so vivisection is a trivial reason. Darwinian arguments have been used to back up each of the three premises above, and, furthermore it has been asserted by animal liberationists that those who do not hold to the evolutionary paradigm are more likely to support vivisection. Here, we present arguments that show why a belief in Darwinism (or in evolution generally) neither strengthens nor weakens the three anti-vivisectionist premises above. We also argue that there is no evidence to suggest that Darwinists are any less (or more) likely to support vivisection than those who hold views on biological origin that are further from the scientific mainstream. By leaving out arguments on origins, we hope that Darwinists, non-Darwinist evolutionists and creationists of all types can work together to make the world a better place for non-human animals.