bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of amyloid β peptides in the regulation of central cholinergic function and its relevance to Alzheimer's disease pathology
Authors: Kar S. 
Published: October 2002

AbstractThe neuropathological features associated with Alzheimer's disease (AD) brain include the presence of extracellular neuritic plaques composed of amyloid β protein (Aβ), intracellular neurofibrillary tangles containing hyperphosphorylated tau protein, and the loss of basal forebrain cholinergic neurons that innervate regions such as the hippocampus and the cortex. Studies of the pathological changes that characterize AD and several other lines of evidence indicate that Aβ accumulation in vivo may initiate and/or contribute to the process of neurodegeneration and thereby the development of AD. However, the mechanisms by which Aβ peptide influences/causes degeneration of the basal forebrain cholinergic neurons and/or the cognitive impairment characteristic of AD remain obscure. A number of recent studies indicate that physiological concentrations of soluble Aβ‐related peptides, under acute conditions, can negatively regulate various steps of acetylcholine (ACh) synthesis and release without inducing any apparent toxicity, suggesting a possible neuromodulatory role for the peptide in the regulation of central cholinergic functions. Chronic exposure to μM concentrations of Aβ peptides, on the other hand, evokes toxicity in cholinergic neurons, possibly via hyperphosphorylation of tau protein. Activation of selected cholinergic receptors has been shown to influence the processing of amyloid precursor protein as well as modulation of tau phosphorylation. More recently, a direct interaction between nicotinic ACh receptor and Aβ peptides have been demonstrated using a variety of approaches. This review focuses on the role of Aβ‐related peptides in the regulation of function/survival of central cholinergic neurons and its relevance to the cholinergic deficits observed in AD brains. Drug Dev. Res. 56:248–263, 2002. © 2002 Wiley‐Liss, Inc.
A numerical study of the behaviour of a gas–liquid interface subjected to periodic vertical motion
Authors: Valha J. , Lewis J. S. , Kubie J. 
Published: October 2002

AbstractA numerical study has been undertaken to examine the behaviour of a gas liquid interface in a vertical cylindrical vessel subjected to a sinusoidal vertical motion. The computational method used is based on the simplified marker‐and‐cell method and includes a continuum surface model for the incorporation of surface tension. The numerical results indicate that the surface tension has very little effect on the period and amplitude of oscillations of the interfacial waves. The stability of the interfacial waves has been found to depend on the initial pressure pulse disturbance, and exponential growth of the interfacial wave has been observed in some cases. The influence of the amplitude and frequency of the forcing oscillations has also been investigated. The results are in good agreement with available experimental and analytical solutions. Copyright © 2002 John Wiley & Sons, Ltd.
Course of minimal dementia and predictors of outcome
Authors: Jelle Visser Pieter , Verhey Frans R. J. , Jolles Jellemer , Jonker Cees 
Published: October 2002

AbstractBackgroundPrevious studies have indicated that not all subjects who meet the CAMDEX criteria of ‘minimal dementia’ progress to dementia. In the present study, predictors of outcome in minimally demented subjects were tested.MethodsForty‐five subjects with minimal dementia who were participating in a population‐based study were followed‐up for on average 2.3 years. Variables tested as predictors of outcome were age, the apolipoprotein E (APOE) genotype, and the baseline scores on the MMSE, CAMCOG memory subscale, and fluency. Depression at baseline was tested as a predictor of reversible minimal dementia.ResultsAt follow‐up, minimal dementia turned out to be reversible in 11 subjects (24%), and persistent in ten subjects (22%). Twenty‐four subjects (53%) had become demented. Predictors of outcome in multivariate analyses were age, score on the CAMCOG memory subscale, and the APOE genotype. Depression was not associated with reversible minimal dementia.ConclusionsSubjects who meet the CAMDEX criteria of minimal dementia form a heterogenous group with respect to clinical outcome. Age, the score on the CAMCOG memory subscale, and the APOE genotype can improve predictive accuracy in these subjects. Copyright © 2002 John Wiley & Sons, Ltd.
Alcoholism in older Korean men: prevalence, aetiology, and comorbidity with cognitive impairment and dementia in urban and rural communities
Authors: Kim Jae‐Min , Shin Il‐Seon , Stewart Robert , Yoon Jin‐Sang 
Published: October 2002

AbstractBackgroundAlcoholism in the elderly has received little research, particularly outside ‘Western’ cultures.ObjectivesThis study aimed to investigate the prevalence and aetiology of alcoholism, and its comorbidity with cognitive impairment and dementia in an older Korean population.Methods1134 urban and rural community residents aged 65 or over were surveyed in Kwangju, South Korea. Alcoholism was identified by a culturally validated screening scale.ResultsAlcoholism was present in 16% of men and 2% of women. In men (n = 457), alcoholism was positively associated with manual occupation and negatively with religions encouraging temperance. In the urban sample, alcoholism was associated with higher education and with dementia. In the rural sample, it was associated with lower education and less strongly with dementia.ConclusionsThe prevalence of alcoholism was high in this population. Associated factors and urban/rural differences reflect traditional attitudes toward drinking. Copyright © 2002 John Wiley & Sons, Ltd.
Hypermethylation of the human telomerase catalytic subunit (hTERT) gene correlates with telomerase activity
Authors: Guilleret Isabelle , Yan Pu , Grange Fabienne , Braunschweig Richard , Bosman Fred T. , Benhattar Jean 
Published: October 2002

AbstractDNA methylation is an epigenetic process involved in embryonic development, differentiation and aging. It is 1 of the mechanisms resulting in gene silencing in carcinogenesis, especially in tumor suppressor genes (e.g., p16, Rb). Telomerase, the DNA polymerase adding TTAGGG repeats to the chromosome end, is involved in the regulation of the replicative life span by maintaining telomere length. This enzyme is activated in germ and stem cells, repressed in normal somatic cells and reactivated in a large majority of tumor cells. The promoter region of the hTERT gene, encoding for the catalytic subunit of human telomerase, has been located in a CpG island and may therefore be regulated at least in part by DNA methylation. We analyzed the methylation status of 27 CpG sites within the hTERT promoter core region by methylation‐sensitive single‐strand conformation analysis (MS‐SSCA) and direct sequencing using bisulfite‐modified DNA in 56 human tumor cell lines, as well as tumor and normal tissues from different organs. A positive correlation was observed among hypermethylation of the hTERT promoter, hTERT mRNA expression and telomerase activity (p < 0.00001). Furthermore, this correlation was confirmed in normal tissues where hypermethylation of the hTERT promoter was found exclusively in hTERT‐expressing telomerase‐positive samples and was absent in telomerase‐negative samples (p < 0.00002). Since tumor tissues contain also nonneoplastic stromal elements, we performed microdissection to allow confirmation that the hTERT promoter methylation truly occurred in tumor cells. Our results suggest that methylation may be involved in the regulation of hTERT gene expression. To our knowledge, this is the first gene in which methylation of its promoter sequence has been found to be positively correlated with gene expression. © 2002 Wiley‐Liss, Inc.
Persistent oxidative stress in colorectal carcinoma patients
Authors: Gackowski Daniel , Banaszkiewicz Zbigniew , Rozalski Rafał , Jawien Arkadiusz , Olinski Ryszard 
Published: October 2002

AbstractWe examine whether the level of 8‐oxo‐2′‐deoxyguanosine (8‐oxodGuo) in lymphocytes DNA is higher in colon cancer when compared to the control group. Factors that may influence oxidative stress such as antioxidant vitamins and uric acid were also determined. Blood samples were obtained from a control group of 55 healthy persons and 43 colon cancers. 8‐OxodGuo level and the vitamins concentration were measured by high‐performance liquid chromatography. The levels of 8‐oxodGuo were significantly higher whereas the concentrations of the vitamins and uric acid were significantly lower in colon cancer patients than in control group. Therefore, the decreased concentration of antioxidant vitamins together with lower amount of uric acid may be responsible for the formation of pro‐oxidative environment in blood of colorectal carcinoma patients. © 2002 Wiley‐Liss, Inc.
E‐cadherin gene variants in gastric cancer families whose probands are diagnosed with diffuse gastric cancer
Authors: Yabuta Tomonori , Shinmura Kazuya , Tani Masachika , Yamaguchi Satoru , Yoshimura Kimio , Katai Hitoshi , Nakajima Takashi , Mochiki Erito , Tsujinaka Toshimasa , Takami Motohisa , Hirose Kazuo , Yamaguchi Akio , Takenoshita Seiichi , Yokota Jun 
Published: October 2002

AbstractTo identify germline E‐cadherin mutations responsible for the predisposition to diffuse gastric cancer (DGC) among the Japanese, we screened 17 patients with familial aggregation of gastric cancer by sequencing analysis. All the patients were diagnosed with DGC and had at least 1 sibling with gastric cancer. Two novel E‐cadherin gene variants were detected. One was detected in 1 patient only and associated with an amino acid substitution (Val/Met) at codon 832 in the region essential for binding to β‐catenin. The M832 variant was detected not only in the proband but also in 2 other gastric cancer patients in the family. Immunohistochemical analysis of gastric cancer tissue from the proband revealed that E‐cadherin expression was markedly reduced and β‐catenin expression was also reduced in cancer cells. However, no significant difference in the activity of β‐catenin binding was detected between the M832 variant and V832 wild‐type E‐cadherin in immunofluorescence and immunoprecipitation/Western blot analyses. The other was detected in 5 patients and was located in the splice donor site (IVS1+6T/C); however, RT‐PCR analysis indicated that the IVS+6C variant did not cause an aberrant splicing. Thus, the M832 variant could be a germline mutation causative of familial aggregation of DGC, although further functional studies are needed to understand the pathogenic significance of this variant. © 2002 Wiley‐Liss, Inc.
In vivo evaluation of hydroxyapatite foams
Authors: Sepulveda P. , Bressiani A. H. , Bressiani J. C. , Meseguer L. , König B. 
Published: October 2002

AbstractHydroxyapatite (HA) is widely applied as bone graft material due to its osteoconductive potential and well‐established biocompatibility. In this work, macroporous hydroxyapatite structures made through foaming of aqueous suspensions and gelcasting were tested for in vivo osteointegration. These foams are composed of a three‐dimensional array of spherical pores with diameters of approximately 100–500 μm, interconnected by windows of smaller size in the range of 30–120 μm. The HA foams were implanted in the tibia of albino New Zealand rabbits and removed after a period of 8 weeks. Histological analysis revealed that the pores in the foams were partially or completely filled progressively with mature new bone tissue and osteoid after the implanted period. No immune or inflammatory reactions were detected. The high osteoconductive potential of the HA foams provides a potential structure for use as bone substitute in orthopedic, oral, and cranio‐maxillofacial reconstructive surgery, and as dento‐alveolar implants. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 587–592, 2002
Adhesion and growth of endothelial cell on amphiphilic PU/PS IPN surface: Effect of amphiphilic balance and immobilized collagen
Authors: Kim J. H. , Kim S. H. , Kim H. K. , Akaike T. , Kim S. C. 
Published: October 2002

AbstractSince natural blood vessels are lined with an endothelial cell (EC) monolayer, it is proposed that synthetic biomaterial surfaces be covered or seeded with endothelial cells for ideal nonthrombogenicity under normal conditions. The effects of the surface energy of hydrophilic‐hydrophobic IPN on EC adhesion and growth were investigated. The human umbilical vein endothelial cells (HUVECs) were cultured on polyurethane (PU)/polystyrene (PS) IPN prepared by changing only the amphiphilic balance and controlling the microphase separated surface structure. The collagens were immobilized on the IPN surfaces for enhanced adhesion of HUVECs, and the morphology of the collagens immobilized highly depended on the surface energy of the IPNs. The stranded rope structure of the collagen molecules in the solution state was maintained only on the surface of the IPN with intermediate hydrophilicity. The adhesion and the proliferation of ECs on the nontreated IPN surfaces increased by increasing the hydrophobicity of the IPNs, and they were optimized on the collagen‐treated IPN surface having an intermediate hydrophilicity. Finally, platelet adhesion was significantly reduced on the EC‐hybridized surface of the IPNs. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 613–621, 2002
Preparation of calcium aluminate cement for hard tissue repair: Effects of lithium fluoride and maleic acid on setting behavior, compressive strength, and biocompatibility
Authors: Oh Seung‐Han , Choi Se‐Young , Lee Yong‐Keun , Kim Kyoung Nam 
Published: October 2002

AbstractWe investigated lithium fluoride (LiF) and maleic acid (MA) containing calcium aluminate cement (CAC) for hard tissue repair. The objective of this study is to estimate the addition effects of LiF and MA on setting behavior, compressive strength, and biocompatibility of CAC and to find the most compatible composition of LiF and MA for using CAC as a new bone cement. The CAC was composed mainly of CaO · Al2O3. Samples of LiF and MA containing CAC were formed along with recording of setting time and peak temperature and then set cement was analyzed by X‐ray diffraction (XRD). Agar diffusion test, tetrazolium bromide (MTT) assay, and hemolysis test were used to detect initial in vitro biocompatibility of LiF and MA containing CAC. It was revealed from the results that LiF shortened setting time and decreased compressive strength, whereas MA delayed setting time and increased compressive strength. However, LiF and MA showed no or little influence on maximum temperature of CAC. CAC containing 0.5 g of LiF and 8.75 g of MA showed the highest compressive strength (111.64 ± 7.74 MPa) across all the experimental compositions. The CACs containing 0.5 g of LiF/8.75 g of MA and 1.01 g LiF/8.75 g of MA had no cytotoxicity and hemolysis. In this study, CAC with 0.5 g of LiF and 8.75g of MA showed the most compatible properties for using bone cement, and thus it was assessed a candidate for a new bone cement along with CAC. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 593–599, 2002
Growth of connective tissue progenitor cells on microtextured polydimethylsiloxane surfaces
Authors: Mata Alvaro , Boehm Cynthia , Fleischman Aaron J. , Muschler George , Roy Shuvo 
Published: October 2002

AbstractGrowth of human connective tissue progenitor cells (CTPs) was characterized on smooth and microtextured polydimethylsiloxane (PDMS) surfaces. Human bone‐marrow‐derived cells were cultured for 9 days under conditions promoting osteoblastic differentiation on smooth PDMS surfaces and on PDMS post microtextures that were 6 μm high and 5, 10, 20, and 40 μm in diameter, respectively. Glass tissue‐culture dishes were used as controls. The number of viable cells was determined, and an alkaline phosphatase stain was used as a marker for osteoblastic phenotype. CTPs attached, proliferated, and differentiated on all surfaces. Cells on the smooth PDMS and control surfaces spread and proliferated as colonies in proximity to other cells and migrated in random directions, with cell process lengths of up to 80 μm. In contrast, cells on the PDMS post microtextures grew as sparsely distributed networks of cells, with processes, occasionally up to 300 μm, that appeared to interact with the posts. Cell counts revealed that there were fewer (50%) CTPs on the smooth PDMS surface than were on the glass control surfaces. However, there were consistently more (>144%) CTPs on the PDMS post textures than on the controls. In particular, the 10‐μm‐in‐diameter posts (268%) exhibited a significantly (p < 0.05) greater cell number than did the smooth PDMS. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 499–506, 2002
Oxidation‐induced dynamic changes in morphology reflected on freeze‐fractured surface of gamma‐irradiated ultra‐high molecular weight polyethylene components
Authors: Watanabe Eiichiro , Suzuki Masahiko , Nagata Kazuya , Kaneeda Toshiaki , Harada Yoshitada , Utsumi Masahiro , Mori Akiko , Moriya Hideshige 
Published: October 2002

AbstractOxidative degradation of ultra‐high molecular weight polyethylene (UHMWPE) attributed to sterilization by gamma‐radiation in the presence of air has been cited as one of the major causes of premature wear in total joint arthroplasty. For example, in retrieved UHMWPE tibial bearings, not only adhesive and abrasive wear, but also fatigue wear characterized by delamination and fracture is frequently observed. In this study, we examined the effects of gamma radiation on the microstructural morphology of UHMWPE tibial bearings, and propose a severe fatigue wear mechanism. Scanning electron microscopic observations were conducted on freeze‐fractured surface of retrieved UHMWPE components that had been sterilized with gamma radiation in air before implantation, unused components that had been stored on the shelf for several years (5–11) after sterilization, and disc specimens given an accelerated aging protocol after gamma radiation. Scanning electron microscopic observations showed that the freeze‐fractured surface of these components had a double layer, which was bordered below the surface. A closer observation of the subsurface layer below the border revealed an extremely rough and porous honeycomb‐like structure. Fourier transform infrared analysis demonstrated that the honeycomb‐like region in the subsurface had a high oxidation level. The internal morphology of oxidized UHMWPE was classified into four categories based on the level of the oxidation. According to these results, the morphological changes with oxidative degradation of gamma‐irradiated UHMWPEs in the presence of air could consistently be explained as the result of major chemical and physical changes such as increased crystallinity, elevated density, and reduced mechanical strength. We relate the morphological changes caused by oxidative degradation in the subsurface to the location of the origin of fatigue wear in total knee joints. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 540–549, 2002
Transfectant mosaic spheroids: a new model for evaluation of tumour cell killing in targeted radiotherapy and experimental gene therapy
Authors: Boyd M. , Mairs S. C. , Stevenson K. , Livingstone A. , Clark A. M. , Ross S. C. , Mairs R. J. 
Published: October 2002

AbstractBackgroundWe describe an in vitro tumour model for targeted radiotherapy and gene therapy that incorporates cell population heterogeneity.Materials and methodsTransfectant mosaic spheroids (TMS) and transfected mosaic monolayers (TMM) are composed of two cell populations derived from a single cell line. The cells of one population were transfected with the noradrenaline transporter gene (NAT), allowing active uptake of a radiolabelled targeting agent meta‐[131I]iodobenzylguanidine ([131I]MIBG); the other population of cells was derived from the same parent line and transfected with a marker gene – green fluorescent protein (GFP). After treatment with [131I]MIBG, cell kill was determined in TMM by clonogenic assay and in TMS by clonogenic assay and spheroid growth delay.ResultsWe have used the TMS model to assess the ‘radiological bystander effect’ (radiation cross‐fire) conferred by the β‐emitting radiopharmaceutical [131I] MIBG whose cellular uptake is facilitated by the transfected gene encoding NAT. We show that cell killing by [131I]MIBG in both TMS and TMM cultures increased in direct proportion to the fraction of NAT‐transfected cells and that the degree of cell killing against fraction transfected was greater in TMS, suggestive of a greater bystander effect in the three‐dimensional culture system.ConclusionsTMS provide a useful model for assessment of the effectiveness of targeted radiotherapy in combination with gene therapy when less than 100% of the target cell population is expressing the NAT transgene. Further, this novel model offers the unique opportunity to investigate radiation‐induced bystander effects and their contribution to cell cytotoxicity in radiotherapy and other gene therapy applications. Copyright © 2002 John Wiley & Sons, Ltd.
Modification of pLL/DNA complexes with a multivalent hydrophilic polymer permits folate‐mediated targeting in vitro and prolonged plasma circulation in vivo
Authors: Ward Christopher M. , Pechar Michal , Oupicky David , Ulbrich Karel , Seymour Leonard W. 
Published: October 2002

AbstractBackgroundGene delivery vectors based on poly(L‐lysine) and DNA (pLL/DNA complexes) have limited use for targeted systemic application in vivo since they bind cells and proteins non‐specifically. In this study we have attempted to form folate‐targeted vectors with extended systemic circulation by surface modification of pLL/DNA complexes with hydrophilic polymers.MethodspLL/DNA complexes were stabilised by surface modification with a multivalent reactive polymer based on alternating segments of poly(ethylene glycol) and tripeptides bearing reactive ester groups. Folate moieties were incorporated into the vectors either by direct attachment of folate to the polymer or via intermediate poly(ethylene glycol) spacers of 800 and 3400 Da.ResultsPolymer‐coated complexes show similar morphology to uncoated complexes, their zeta potential is decreased towards zero, serum protein binding is inhibited and aqueous solubility is substantially increased. Intravenous (i.v.) administration to mice of coated complexes produced extended systemic circulation, with up to 2000‐fold more DNA measured in the bloodstream after 30 min compared with simple pLL/DNA complexes. In further contrast to simple pLL/DNA complexes, coated complexes do not bind blood cells in vivo. Folate receptor targeting is shown to mediate targeted association with HeLa cells in vitro, leading to increased transgene expression. We demonstrate for the first time that DNA uptake via the folate receptor is dependent on pEG spacer length, with the transgene expression relatively independent of the level of internalised DNA.ConclusionsWe show increased systemic circulation, decreased blood cell and protein binding, and folate‐targeted transgene expression using pLL/DNA complexes surface‐modified with a novel multireactive hydrophilic polymer. This work provides the basis for the development of plasma‐circulating targeted vectors for in vivo applications. Copyright © 2002 John Wiley & Sons, Ltd.