bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impairment of hippocampal long‐term depression and defective spatial learning and memory in p35–/– mice
Authors: Ohshima Toshio , Ogura Hiroo , Tomizawa Kazuhito , Hayashi Kanehiro , Suzuki Hiromi , Saito Taro , Kamei Hirotsugu , Nishi Akinori , Bibb James A. , Hisanaga Shin‐ichi , Matsui Hideki , Mikoshiba Katsuhiko 
Published: July 2005

AbstractCdk5 (cyclin‐dependent kinase 5) activity is dependent upon association with one of two neuron‐specific activators, p35 or p39. Genetic deletion of Cdk5 causes perinatal lethality with severe defects in corticogenesis and neuronal positioning. p35–/– mice are viable with milder histological abnormalities. Although substantial evidence implicates Cdk5 in synaptic plasticity, its role in learning and memory has not been evaluated using mutant mouse models. We report here that p35–/– mice have deficiencies in spatial learning and memory. Close examination of hippocampal circuitry revealed subtle histological defects in CA1 pyramidal cells. Furthermore, p35–/– mice exhibit impaired long‐term depression and depotentiation of long‐term potentiation in the Schaeffer collateral CA1 pathway. Moreover, the Cdk5‐dependent phosphorylation state of protein phosphatase inhibitor‐1 was increased in 4‐week‐old mice due to increased levels of p39, which co‐localized with inhibitor‐1 and Cdk5 in the cytoplasm. These results demonstrate that p35‐dependent Cdk5 activity is important to learning and synaptic plasticity. Deletion of p35 may shift the substrate specificity of Cdk5 due to compensatory expression of p39.
Chronic hyperammonemia in vivo impairs long‐term potentiation in hippocampus by altering activation of cyclic GMP‐dependent‐protein kinase and of phosphodiesterase 5
Authors: Monfort Pilar , Muñoz María‐Dolores , Felipo Vicente 
Published: July 2005

AbstractLong‐term potentiation (LTP) is impaired in the CA1 area of hippocampal slices from rats with chronic moderate hyperammonemia. We studied the mechanisms by which hyperammonemia in vivo impairs LTP. This process requires sequential activation of soluble guanylate cyclase, cyclic GMP‐dependent protein kinase (PKG) and cyclic GMP‐degrading phosphodiesterase. Application of the tetanus induced a rapid increase of cyclic GMP in slices from control or hyperammonemic rats, which is followed in control slices by a sustained decrease in cyclic GMP due to sustained activation of cyclic GMP‐degrading phosphodiesterase, which in turn is due to sustained activation of PKG. In slices from rats with chronic hyperammonemia tetanus‐induced decrease in cyclic GMP was delayed and transient due to lower and transient activation of PKG and of the phosphodiesterase. Hyperammonemia‐induced impairment of LTP may be involved in the alterations of cognitive function in patients with hepatic encephalopathy.
Why do Nogo/Nogo‐66 receptor gene knockouts result in inferior regeneration compared to treatment with neutralizing agents?
Authors: Teng Felicia Yu Hsuan , Tang Bor Luen 
Published: July 2005

AbstractIN‐1, the monoclonal antibody against the exon 3‐encoded N‐terminal domain of Nogo‐A, and the Nogo‐66 receptor (NgR) antagonist NEP1‐40 have both shown efficacy in promoting regeneration in animal spinal cord injury models, the latter even when administered subcutaneously 1 week after injury. These results are supportive of the hypothesis that the Nogo–NgR axis is a major path for inhibition of spinal cord axonal regeneration and uphold the promises of these neutralizing agents in clinical applications. However, mice with targeted disruption of Nogo and NgR have, surprisingly, only modest regenerative capacity (if any) compared with treatment with IN‐1 or NEP1‐40. Disruption of the Nogo gene by various groups yielded results ranging from significant regenerative improvement in young mice to no improvement. Likewise, knockout of NgR produced some improvement in raphespinal and rubrospinal axonal regeneration, but not that of corticospinal neurons. Other than invoking possible differences in genetic background, we suggest here some possible and testable explanations for the above phenomena. These possibilities include effects of IN‐1 and NEP1‐40 on the CNS beyond neutralization of Nogo and NgR functions, and the latter's possible role in the CNS beyond that of neuronal growth inhibition.
Activation of calcium‐independent phospholipase A2 (iPLA2) in brain mitochondria and release of apoptogenic factors by BAX and truncated BID
Authors: Brustovetsky Tatiana , Antonsson Bruno , Jemmerson Ronald , Dubinsky Janet M. , Brustovetsky Nickolay 
Published: July 2005

AbstractCleaved or truncated BID (tBID) is known to oligomerize both BAK and BAX. Previously, BAK and BAX lacing the C‐terminal fragment (BAXΔC) were shown to induce modest cytochrome c (Cyt c) release from rat brain mitochondria when activated by tBID. We now show that tBID plus monomeric full‐length BAX induce extensive release of Cyt c, Smac/DIABLO, and Omi/HtrA2 (but not endonuclease G and the apoptosis inducing factor) comparable to the release induced by alamethicin. This occurs independently of the permeability transition without overt changes in mitochondrial morphology. The mechanism of the release may involve formation of reactive oxygen species (ROS) and activation of calcium‐independent phospholipase A2 (iPLA2). Indeed, increased ROS production and activated iPLA2 were observed prior to massive Cyt c release. Furthermore, the extent of inhibition of Cyt c release correlated with the degree of suppression of iPLA2 by the inhibitors propranolol, dibucaine, 4‐bromophenacyl bromide, and bromenol lactone. Consistent with a requirement for iPLA2 in Cyt c release from brain mitochondria, synthetic liposomes composed of lipids mimicking the outer mitochondrial membrane (OMM) but lacing iPLA2 failed to release 10 kDa fluorescent dextran (FD‐10) in response to tBID plus BAX. We propose that tBID plus BAX activate ROS generation, which subsequently augments iPLA2 activity leading to changes in the OMM that allow translocation of certain mitochondrial proteins from the intermembrane space.
α‐Linolenic acid does not contribute appreciably to docosahexaenoic acid within brain phospholipids of adult rats fed a diet enriched in docosahexaenoic acid
Authors: DeMar James C. , Ma Kaizong , Chang Lisa , Bell Jane M. , Rapoport Stanley I. 
Published: July 2005

AbstractAdult male unanesthetized rats, reared on a diet enriched in both α‐linolenic acid (α‐LNA) and docosahexaenoic acid (DHA), were infused intravenously for 5 min with [1‐14C]α‐LNA. Timed arterial samples were collected until the animals were killed at 5 min and the brain was removed after microwaving. Plasma and brain lipid concentrations and radioactivities were measured. Within plasma lipids, > 99% of radioactivity was in the form of unchanged [1‐14C]α‐LNA. Eighty‐six per cent of brain radioactivity at 5 min was present as β‐oxidation products, whereas the remainder was mainly in ‘stable’ phospholipid or triglyceride as α‐LNA or DHA. Equations derived from kinetic modeling demonstrated that unesterified unlabeled α‐LNA rapidly enters brain from plasma, but that its incorporation into brain phospholipid and triglyceride, as in the form of synthesized DHA, is ≤ 0.2% of the amount that enters the brain. Thus, in rats fed a diet containing large amounts of both α‐LNA and DHA, the α‐LNA that enters brain from plasma largely undergoes β‐oxidation, and is not an appreciable source of DHA within brain phospholipids.
High‐affinity peripheral benzodiazepine receptor ligand, PK11195, regulates protein phosphorylation in rat brain mitochondria under control of Ca2+
Authors: Azarashvili T. , Krestinina O. , Yurkov I. , Evtodienko Y. , Reiser G. 
Published: July 2005

AbstractThe effects of PK11195, a high‐affinity peripheral benzodiazepine receptor (PBR) ligand, on protein phosphorylation in isolated purified rat brain mitochondria were investigated. The isoquinoline carboxamide ligand of PBR, PK11195, but not the benzodiazepine ligand Ro5–4864, in the nanomolar concentration range strongly increased the phosphorylation of 3.5 and 17 kDa polypeptides. The effect of PK11195 was seen in the presence of elevated Ca2+ levels (3 × 10−7 to 10−6 m), but not at very low Ca2+ levels (10‐8 to 3 × 10−8 m). This indicates that PBR involves Ca2+ as a second messenger in the regulation of protein phosphorylation. Staurosporine, an inhibitor of protein kinase activity was able to suppress the PK11195‐promoted protein phosphorylation. When the permeability transition pore (PTP) was opened by threshold Ca2+ load, phosphorylation of the 3.5‐kDa polypeptide was diminished, but strong phosphorylation of the 43‐kDa protein was revealed. The 43‐kDa protein appears to be a PTP‐specific phosphoprotein. If PTP was opened, PK11195 did not increase the phosphorylation of the 3.5 and 17‐kDa proteins but suppressed the phosphorylation of the PTP‐specific 43‐kDa phosphoprotein. The ability of PK11195 to increase the protein phosphorylation, which was lost under Ca2+‐induced PTP opening, was restored again in the presence of calmidazolium, an antagonist of calmodulin and inhibitor of protein phosphatase PP2B. These results show a tight interaction of PBR with the PTP complex in rat brain mitochondria. In conclusion, a novel function of PBR in brain mitochondria has been revealed, and the PBR‐mediated protein phosphorylation has to be considered an important element of the PBR‐associated signal transducing cascades in mitochondria and cells.
Protective human immunity as a vaccine discovery tool for falciparum malaria
Authors: Nixon Christian P. , Friedman Jennifer F. , Knopf Paul M. , Duffy Patrick E. , Kurtis Jonathan D. 
Published: July 2005

BACKGROUND:  Plasmodium falciparum malaria remains a leading cause of morbidity and mortality in developing countries, and malaria‐associated severe anemia is the major factor driving the high transfusion requirements in pediatric populations living in endemic areas.STUDY DESIGN AND METHODS:  In this report, we identify and evaluate the targets of naturally acquired protective antibody responses in a cohort of n = 143 male volunteers residing in a P. falciparum holoendemic area of western Kenya. Volunteers were drug‐cured of current malaria infection, blood was collected 2 weeks after treatment, and blood smears were collected weekly for 18 weeks. We identified and pooled plasma from the 10 most resistant (RP) and the 7 most susceptible individuals (SP) and utilized these pools in a differential screen of a P. falciparum cDNA expression library. We screened 550,000 clones and identified 7 clones that were uniquely recognized by RP but not by SP. Two clones encoded a C‐terminal region polypeptide from rhoptery‐associated membrane antigen (RAMA‐pr), a recently described rhoptry‐associated membrane antigen.RESULTS:  We measured RAMA‐pr antibody levels in plasma obtained 2 weeks after treatment. Individuals with detectable immunoglobulin G1 anti‐RAMA‐pr (n = 24) had fewer positive blood films (p < 0.003) and 43 percent lower density of parasitemia (p < 0.02) than individuals with undetectable (n = 115) antibody levels.CONCLUSION:  RAMA‐pr is a rationally identified vaccine candidate preferentially recognized by antibodies produced by humans with a high level of naturally acquired resistance to P. falciparum infection. Our results demonstrate that naturally acquired protective antibody responses are useful tools to identify vaccine candidates for falciparum malaria.
Oral precancerous disorders associated with areca quid chewing, smoking, and alcohol drinking in southern Taiwan
Authors: Chung Ching‐Hung , Yang Yi‐Hsin , Wang Tung‐Yiu , Shieh Tien‐Yu , Warnakulasuriya Saman 
Published: July 2005

Objective:  To investigate the prevalence and the associated risk factors of oral precancerous disorders in southern Taiwan.Methods:  We conducted a cross‐sectional community survey interviewing 1075 adult subjects, 15 years of age and over, gathered from randomly selected 591 households, and spanning five villages in southern Taiwan. The study protocol included a visual oral soft tissue examination and a questionnaire‐based interview. The chi‐square test was used to test the differences in prevalence of oral precancerous lesions and conditions by different ‘life styles’ relating to current risk habits of current areca quid chewing, smoking, and alcohol drinking. To control for possible confounding, a logistic regression model was used to estimate the Odds Ratios (OR) for leukoplakia and oral submucous fibrosis (OSF).Results:  136 precancerous lesions and conditions were detected among 1075 subjects (12.7%). The analysis of the spectrum of oral precancerous disorders detected, leukoplakia (n = 80), OSF (n = 17) and verrucous lesions (n = 9), demonstrated an association with gender (P < 0.001). There were statistically significant associations among leukoplakia (P < 0.01), OSF (P < 0.0001), and verrucous lesions (P < 0.0001) and the life style of current areca quid chewing, smoking, and alcohol drinking. The synergistic effect of smoking and areca quid chewing habit on leukoplakia and OSF was demonstrated.Conclusion:  This study reinforces the association of current areca quid chewing without tobacco, cigarette smoking, and alcohol drinking to leukoplakia, OSF, and verrucous lesions in Taiwan.
A clinical study of 674 patients with oral lichen planus in China
Authors: Xue Jing‐Ling , Fan Ming‐Wen , Wang Shuo‐Zhi , Chen Xin‐Ming , Li Yuan , Wang Li 
Published: July 2005

Background:  Oral lichen planus (OLP) is a chronic inflammatory disease with different clinical presentations that can be classified as reticular, atrophic or erosive. Although OLP is a relatively common disorder, the reports comprising large numbers of OLP patients with specific character are lacking in the literature. The purpose of this paper was to describe the clinical characteristics of OLP in 674 Chinese patients.Methods:  A total of 674 charts of patients with histologically confirmed OLP were collected from Stomatological Hospital of Wuhan University between 1963 and 2003.Results:  Of the 674 patients, 65.9% were women and 34.1% were men. The most common clinical presentation was the reticular type (51.3%), and symptomatic OLP was noted in 67.5% of the patients, mainly in those with the erosive form. The erosive presentations showed significantly longer duration, more sites affected and a much greater old patients predominance than reticular or atrophic ones. About 90.9% of the patients had multiple oral sites of involvement and isolated lower lip lichen planus were observed in 60 cases (8.9%) and isolated gingiva lichen in only one case (0.2%). Skin involvement of lichen planus was found in 11.4% of patients. No statistically significant differences could be identified between OLP and diabetes, cardiovascular disease, smoking or alcohol use. Precipitating factors that resulted in an exacerbation of the disease were frequently noted and included foods, stress, dental cusp and poor oral hygiene. The transformation of OLP into malignancy was observed in four patients at sites previously diagnosed by clinical examination as erosive or atrophic lichen planus.Conclusions:  Patients with OLP in China usually present with distinctive clinical morphology and characteristic distribution and few may display lesions with a confusing array of forms mimicking other diseases. A long time follow up is of utmost importance to detect its malignant transformation.
Association of GST genotypes with age of onset and lymph node metastasis in oral squamous cell carcinoma
Authors: Liu Chung‐Ji , Chang Che‐Shoa , Lui Man‐Tin , Dang Ching‐Wen , Shih Yin‐Hua , Chang Kuo‐Wei 
Published: July 2005

Background:  Environment–gene interaction in oral carcinogenesis is well demonstrated by phase I and II enzymes that are involved in the metabolism of carcinogens. This study investigated the association of glutathione S‐transferase (GST)T1 and GSTM1 genotypes of phase II enzyme genes with risk for, age of onset, and neck lymph node metastasis (LNM) in areca‐associated oral squamous cell carcinoma (OSCC).Methods:  A total of 114 OSCC male patients and 100 male controls were recruited. All subjects were areca users and tobacco smokers. DNA was obtained from peripheral blood samples. Genotyping of GSTT1 (non‐null/null) and GSTM1 (non‐null/null) was determined by polymerase chain reaction (PCR) analysis using specific primers that only amplify non‐null alleles.Results:  No association was found between GST genotype and the risk of OSCC based on case–controls. Patients with the GSTT1 null genotype were older at onset (P = 0.03). Those with the GSTM1 null genotype had a higher incidence of neck LNM than those with the GSTM1 non‐null genotype (P = 0.01). Patients with the GSTM1/GSTT1 null genotype appeared to have later onset and a higher incidence of neck LNM than those carrying the opposite genotype.Conclusion:  The GST genotypes may be important markers for the age of onset and risk of metastasis in OSCC. The data also suggest that the various GST isoforms may be differentially involved in development or progression of OSCC.
Cleavage of nucleolin and AgNOR proteins during apoptosis induced by anticancer drugs in human salivary gland cells
Authors: Kito S. , Morimoto Y. , Tanaka T. , Haneji T. , Ohba T. 
Published: July 2005

Background:  To investigate the behavior of nuclear proteins in apoptosis induced by anticancer drugs in cultured human salivary gland (HSG) cells.Methods:  Dynamic alternations of nucleolin and argyrophilic nucleolar organizer region (AgNOR) proteins in anticancer drug‐induced apoptosis of HSG cells and in a cell‐free apoptotic system were examined using Western blot analysis and immunocytochemical method.Results:  The 110‐kDa form of nucleolin and AgNOR protein decreased and the 80‐ and 95‐kDa forms appeared during apoptosis in HSG cells and in a cell‐free apoptotic system. In addition, the induction of DNA ladder formation coincided with the appearance of alternation of nucleolin and AgNOR proteins in a cell‐free apoptosis. Nucleolin diffusely spread out into the nuclear material in the apoptotic body of HSG cells.Conclusions:  The present results indicate that alternations of nucleolin and AgNOR proteins are associated with the induction of DNA fragmentation and the final active phase of apoptosis induced by anticancer drugs in malignant salivary gland cells.
Why Look at Elephants?
Authors: Rothfels Nigel 
Published: July 2005

AbstractThrough analysis of the contending ways elephants have been imagined in a mid twentieth-century circus performance and in a mid nineteenth-century hunting narrative, this essay offers a critique of several basic assumptions behind John Berger's "Why Look at Animals?" The paper argues that studying how elephants have been described and used reveals particularly well the often quickly evolving nature of our understanding of animals and their significance in our lives, and concludes that our historical comprehension of the very terms of "animal" and "human" is often surprisingly complex.
John Berger's "Why Look at Animals?": A Close Reading
Authors: Burt Jonathan 
Published: July 2005

AbstractThis article is a close reading of John Berger's highly influential essay "Why look at animals?" and its implications for thinking about animals in modernity. Berger analyses the alienation of human and animal as a consequence of nineteenth-century capitalism, and contrasts it with an earlier period when human-animal relations were more integrated. Despite the power and simplicity of Berger's argument, which has been taken up uncritically by a number of writers, both his historical analysis and his conception of human-animal relations in modernity are highly problematic and need substantial revision. Furthermore, the consequences of his thesis paradoxically reinforce the very processes he is criticising. Inadequate notions of the place of animals in public visual culture, and a more general bias against visual imagery in favour of text-based notions of the animal, create obstacles to theorising human-animal relations and welfare related issues in the contemporary world. The article suggests other perspectives for understanding what it means to look at animals.
Inventing a Beast with No Body: Radio-Telemetry, the Marginalization of Animals, and the Simulation of Ecology
Authors: Bergman Charles 
Published: July 2005

AbstractRadio-telemetry is a relatively new technology that is having powerful impacts on the way wildlife is studied. With tens of thousands of new radio-telemetry units produced each year, to be placed on animals in the wild, it is a technology that is becoming increasingly pervasive. This paper begins by examining the way radio-telemetry has been adapted for the study of macaws in Latin America. The paper argues that as a form of surveillance and monitoring, radio-telemetry illustrates some ways in which Michel Foucault's concepts of "biopower" and surveillance can be applied to the management of wildlife. Additionally, as the new technology creates a greater sense of distance between the "sign" of a creature and its actual reality, wild animals seem to become what Jean Baudrillard terms "simulations", in which they are increasingly signs of their own disappearance—both as creatures and as species.
Results of a phase 1 clinical trial of thalidomide in combination with fludarabine as initial therapy for patients with treatment-requiring chronic lymphocytic leukemia (CLL)
Authors: Chanan-Khan Asher , Miller Kena C. , Takeshita Kenichi , Koryzna Alexandra , Donohue Kathleen , Bernstein Zale P. , Mohr Alice , Klippenstein Donald , Wallace Paul , Zeldis Jerome B. , Berger Christine , Czuczman Myron S. 
Published: July 2005

AbstractTumor necrosis factor α (TNF-α) and vascular endothelial growth factor (VEGF) play an important role in the biology of chronic lymphocytic leukemia (CLL) cells. Thalidomide is a first-generation immuno-modulating agent that down-regulates TNF-α and VEGF. We initiated a phase 1/2 clinical trial to determine the safety and efficacy of combining thalidomide with fludarabine in patients with treatment-naïve CLL. Patients received 6 months of continuous daily thalidomide with standard monthly doses of fludarabine. Three dose levels of thalidomide (100, 200, and 300 mg) were studied. Results from the phase 1 part of this study are reported here. Thirteen patients were enrolled in the phase 1 component of the study. Dose-limiting toxicity was not reached. The most common toxicities noted were fatigue, constipation, and peripheral sensory neuropathy. Overall response rate was 100% with 55% of patients achieving complete remissions. At a median follow-up of 15+ months none of the patients have had a relapse and the median time to disease progression has not yet been reached. Responses were noted at all dose levels. Thalidomide given up to 300 mg/day concurrently with fludarabine in patients with previously untreated CLL shows encouraging clinical efficacy and acceptable toxicity. An ongoing phase 2 part of this study will help validate the clinical efficacy of this regimen.