bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contribution of NMDA receptor channels to the expression of LTP in the hippocampal dentate gyrus
Authors: Wang Zhuo , Song Dong , Berger Theodore W. 
Published: October 2002

AbstractThe role of glutamatergic NMDA receptor channels (NMDARs) in the induction of long‐term potentiation (LTP) has been well established. In contrast, whether or not NMDARs contribute to the expression of LTP has been an issue of debate. In this study, we investigated the contribution of NMDARs to LTP expression in the hippocampal dentate gyrus (DG) by stimulating perforant path afferents with short bursts of pulses delivered at a moderate frequency (40 Hz), instead of using the traditional protocol of a single stimulus at a low frequency (<0.1 Hz). The synaptic summation provided by the “burst” protocol enabled us to measure the NMDAR‐mediated component of synaptic responses (NMDA component), defined as the NMDAR antagonist D‐2‐amino‐5‐phosphonovalerate (APV)‐sensitive component, in the presence of physiological concentrations of Mg2+ (1 mM). Intracellular recordings were obtained from DG granule cells of rabbit hippocampal slices, and excitatory postsynaptic potentials (EPSPs) were measured in terms of the integrated area of their profiles. At 40 Hz, frequency facilitation of the evoked EPSPs was observed. The NMDA component gradually increased during the five‐pulse train and frequency facilitation was significantly reduced after the application of APV. We tested the hypothesis that NMDARs undergo potentiation in LTP by comparing the NMDA/non‐NMDA ratio of the synaptic responses in control and LTP groups. An increase in the ratio was observed in the LTP group, strongly suggesting potentiation of NMDARs. To infer changes in conductance at individual synapses based on EPSPs recorded at the soma, we constructed a compartmental model of a morphologically reconstructed DG granule cell. The effect on the NMDA/non‐NMDA ratio of changes in AMPA and NMDA component synaptic conductance, and of differences in the distribution of activated synapses, was studied with computer simulations. The results confirmed that NMDARs are potentiated after the induction of LTP and contribute significantly to the expression of potentiation under physiological conditions. Hippocampus 2002;12:680–688. © 2002 Wiley‐Liss, Inc.
Contribution of T‐type VDCC to TEA‐induced long‐term synaptic modification in hippocampal CA1 and dentate gyrus
Authors: Song Dong , Wang Zhuo , Berger Theodore W. 
Published: October 2002

AbstractWe have previously reported that exposure to the K+ channel blocker tetraethylammonium (TEA), 25 mM, induces long‐term potentiation (LTP) in CA1, but not in the dentate gyrus (DG), of the rat hippocampal slice. During TEA application, stimulation of excitatory afferents results in a strong depolarizing potential after the fast excitatory postsynaptic potential (EPSP) in CA1, but not in DG. We hypothesized that the differential effect of TEA on long‐term synaptic modification in CA1 and DG results from different levels of TEA‐elicited depolarization in the two cell types. Additional pharmacological studies showed that blockade of T‐type voltage‐dependent calcium channels (VDCCs) decreased both the magnitude of LTP and the late, depolarizing potential in CA1. Blockade of L‐type VDCCs had no such effect. Using computer models of morphologically reconstructed CA1 pyramidal cells and DG granule cells, we tested our hypothesis by simulating the relative intracellular Ca2+ accumulation and membrane potential changes mediated by T‐type and L‐type VDCCs. Simulation results using pyramidal cell models showed that, with decreased maximum conductance of TEA‐sensitive potassium channels, synaptic inputs elicited strong depolarizing potentials similar to those observed with intracellular recording. During this depolarization, VDCCs were opened and resulted in a large intracellular Ca2+ accumulation that presumably caused LTP. When T‐type VDCCs were blocked, the magnitudes of both the Ca2+ accumulation and the late depolarizing potential were decreased substantially. Simulated blockade of L‐type VDCCs had only a minor effect. Together, our modeling and experimental studies indicate that T‐type VDCCs, rather than L‐type VDCCs, are primarily responsible for facilitating the depolarizing potential caused by TEA and for the consequent Ca2+ influx. Thus, our findings strongly suggest that the induction of TEA‐LTP in CA1 depends primarily on T‐type, rather than L‐type, VDCCs. Simulation results using modeled granule cells suggests that the failure of TEA to induce LTP in DG is partly due to a low density of T‐type VDCCs in granule cell membranes. Hippocampus 2002;12:689–697. © 2002 Wiley‐Liss, Inc.
Hierarchical model of the population dynamics of hippocampal dentate granule cells
Authors: Chauvet G.A. , Berger T.W. 
Published: October 2002

AbstractA hierarchical modeling approach is used as the basis for a mathematical representation of the population activity of hippocampal dentate granule cells. Using neural field equations, the variation in time and space of dentate granule cell activity is derived from the summed synaptic potential and summed action potential responses of a population of granule cells evoked by monosynaptic excitatory input from entorhinal cortical afferents. In this formulation of the problem, we have considered a two‐level hierarchy: the synapses of entorhinal cortical axons define the first level of organization, and dentate granule cells, which include these synapses, define the second, higher level of organization. The model is specified by two state field variables, for membrane potential and for synaptic efficacy, respectively, with both evolving according to different time scales. The two state field variables introduce new parameters, physiological and anatomical, which characterize the dentate from the point of view of neuronal and synaptic populations: (1) a set of geometrical constraints corresponding to the morphological properties of granule cells and anatomical characteristics of entorhinal‐dentate connections; and (2) a set of neuronal parameters corresponding to physiological mechanisms. Assuming no interaction between granule cells, i.e., neither ephaptic nor synaptic coupling, the model is shown to be mathematically tractable and allows solution of the field equations leading to the determination of activity. This treatment leads to the definition of two state variables, volume of stimulated synapses and firing time, which describe observed activity. Numerical simulations are used to investigate the populational characterization of the dentate by individual parameters: (1) the relationship between the conditions of stimulation of active perforant path fibers, e.g., stimulating intensity, and activity in the granule cell layer; and (2) the influence of geometry on the generation of activity, i.e., the influence of neuron density and synaptic density‐connectivity. As an example application of the model, the granule cell population spike is reconstructed and compared with experimental data. Hippocampus 2002;12:698–712. © 2002 Wiley‐Liss, Inc.
New life in an old idea: The synaptic plasticity and memory hypothesis revisited
Authors: Martin S.J. , Morris R.G.M. 
Published: October 2002

AbstractThe notion that changes in synaptic efficacy underlie learning and memory processes is now widely accepted, although definitive proof of the synaptic plasticity and memory hypothesis is still lacking. This article reviews recent evidence relevant to the hypothesis, with particular emphasis on studies of experience‐dependent plasticity in the neocortex and hippocampus. In our view, there is now compelling evidence that changes in synaptic strength occur as a consequence of certain forms of learning. A major challenge will be to determine whether such changes constitute the memory trace itself or play a less specific supporting role in the information processing that accompanies memory formation. Hippocampus 2002;12:609–636. © 2002 Wiley‐Liss, Inc.
A new method of implanting orthotopic rat bladder tumor for experimental therapies
Authors: Bisson Jean‐François , Parache Robert M. , Droulle Pierre , Notter Dominique , Vigneron Claude , Guillemin François 
Published: October 2002

AbstractWe developed a model of orthotopic transplantation of bladder tumor cells in female Fischer rats using a new reproducible technique. After first performing the mechanical abrasion of a portion of the bladder urothelium with an Abrader© inserted transurethrally via a catheter, we administered a suspension of 5–40 × 106 viable AY‐27 tumor cells in sterile phosphate‐buffered saline to the bladder cavity. This rapidly led to a tumor growth incidence of approximately 100%. The induced bladder tumors grew expansively into the bladder cavity from the surface (mucosa) and gradually invaded the submucosa, muscles, serosa and surrounding tissue (high‐stage invasive transitional cell carcinoma). Size and staging were related to the quantity of tumor cells instilled into the bladder cavity. This model matches the characteristics of human bladder tumor more closely than other bladder cancer models induced with tumor cells. Moreover, it presents many advantages: the method is reproducible, tumors grow rapidly, they are directly attached to the bladder surface and they are always located on the bladder wall, in line with the urethra. This proves especially helpful for evaluating chemotherapeutic agents by different means such as in vivo fluorescence spectroscopy, a noninvasive method used in photodynamic therapy, or other methods designed to detect and treat transitional cell carcinoma. © 2002 Wiley‐Liss, Inc.
Frequent chromosome 9p losses in histologically normal nasopharyngeal epithelia from southern Chinese
Authors: Chan Andrew Siu Chung , To Ka Fai , Lo Kwok Wai , Ding Min , Li Xianghong , Johnson Philip , Huang Dolly Poon 
Published: October 2002

AbstractNasopharyngeal carcinoma (NPC) is a common cancer among the Chinese population in the southern part of China. The incidence of this cancer drops markedly in northern China. A 6‐ to 24‐fold difference exists between southern and northern Chinese. To investigate the early genetic events involved in the development of this cancer, we have examined loss of heterozygosity (LOH) on chromosome 9p, being one of the most frequent genetic alterations in NPC, in nasopharyngeal tissues including normal epithelia (NP), dysplastic lesions (DNP) and invasive carcinoma (NPC) from high‐risk and low‐risk regions. We found similar frequencies of 9p LOH in NPC from high‐risk (77.8%) and low‐risk (63.6%) regions (p = 0.43). In contrast, 45% of normal nasopharyngeal epithelia from the high‐risk region showed 9p LOH, while none of the NP from the low‐risk region showed such abnormalities (p = 0.002). Deletions of chromosome 9p were found in 66.7% dysplastic nasopharyngeal lesions. These findings suggest that LOH of chromosome 9p is an early event in the tumorigenesis of NPC. The increased risk of NPC in southern Chinese may be related to early loss of genetic materials as indicated by 9p LOH in the NP from high‐ and low‐risk regions. We also reported previously that Epstein‐Barr virus (EBV) latent infection was present in all high‐grade DNP and NPC but not in any NP from fetuses or normal adults. Thus, early genetic alterations such as 9p LOH may take place prior to EBV latent infection and expand clonally thereafter. © 2002 Wiley‐Liss, Inc.
A proposal for cervical screening information systems in developing countries
Authors: Marrett Loraine D. , Robles Sylvia , Ashbury Fredrick D. , Green Bo , Goel Vivek , Luciani Silvana 
Published: October 2002

AbstractThe effective and efficient delivery of cervical screening programs requires information for planning, management, delivery and evaluation. Specially designed systems are generally required to meet these needs. In many developing countries, lack of information systems constitutes an important barrier to development of comprehensive screening programs and the effective control of cervical cancer. Our report outlines a framework for creating such systems in developing countries and describes a conceptual model for a cervical screening information system. The proposed system is modular, recognizing that there will be considerable between‐region heterogeneity in current status and priorities. The proposed system is centered on modules that would allow for the assembly and computerization of data on Pap tests, since these represent the main screening modality at the present time. Additional modules would process data and create and maintain a screening database (e.g., standardize, edit, link and update modules) and allow for the integration of other types of data, such as cervical histopathology results. An open systems development model is proposed, since it is most compatible with the goals of local stakeholder involvement and capacity‐building. © 2002 Wiley‐Liss, Inc.
Long‐term effects of oral contraceptives on ovarian cancer risk
Authors: Bosetti Cristina , Negri Eva , Trichopoulos Dimitrios , Franceschi Silvia , Beral Valerie , Tzonou Anastasia , Parazzini Fabio , Greggi Stefano , La Vecchia Carlo 
Published: October 2002

AbstractSeveral epidemiologic studies have reported a protective effect of oral contraceptives (OCs) on ovarian cancer. However, there remain open issues, including better quantification of time‐related factors such as time since last use, age at first use and time since first use. We performed a collaborative reanalysis of 6 case‐control studies conducted between 1978 and 1999 in the United Kingdom, Greece and Italy, including a total of 2,768 incident, histologically confirmed cases of epithelial ovarian cancer and 6,274 hospital controls under age 70 years. A reduced risk of ovarian cancer was found for ever‐ compared to never‐users [odds ratio (OR) = 0.66, 95% confidence interval (CI) 0.56–0.79], and a stronger reduction was observed for women who had used OCs for ≥5 years (OR = 0.50, 95% CI 0.33–0.76) compared to those who had used them for <5 years. The protective effect of OCs on ovarian cancer was consistent across strata of age, parity, menopausal status and family history of breast or ovarian cancer. After allowance for duration of use, no other time factor was related to ovarian cancer risk: the reduced risk was similar for women who stopped OC use ≥20 years before compared to <10 years; likewise, no significant modification of risk reduction was observed for age at first OC use and time since first OC use. The present analysis indicates that, after taking into account duration of OC use, the OC protection from ovarian cancer persists for a long time after stopping use. © 2002 Wiley‐Liss, Inc.
Oesophageal adenocarcinoma: A paradigm of mechanical carcinogenesis?
Authors: La Vecchia Carlo , Negri Eva , Lagiou Pagona , Trichopoulos Dimitrios 
Published: October 2002

AbstractIncidence of adenocarcinoma of the oesophagus and gastric cardia is increasing in most developed countries and strongly associated with obesity and male gender. An underlying increase in the prevalence of gastro‐oesophageal reflux has generally been postulated. We suggest that the increase in frequency of reflux and the 2 associated forms of cancer can be explained by growing abdominal pressure brought about by increasing central obesity, most common among men, and sedentary lifestyle, including car use. Abdominal pressure is further accentuated mainly in men by the shift in Western male dressing towards the general use of belts. © 2002 Wiley‐Liss, Inc.
Relationship of uveal and cutaneous malignant melanoma in persons with multiple primary tumors
Authors: Shors Andrew R. , Iwamoto Satori , Doody David R. , Weiss Noel S. 
Published: October 2002

AbstractUveal and cutaneous melanomas differ in tumor biology, immunophenotypes and the demographic correlates of their occurrence. As a means to examine the possibility of some shared etiologic factors, we wished to learn if the 2 cancers occurred in the same individual more often than would be expected by chance. Data from the Surveillance, Epidemiology and End Results (SEER) program from 1973–1998 were utilized for this purpose. The number of persons who went on to develop a second melanoma was compared to that expected based on the incidence of each type of melanoma in the general population, after adjusting for age, sex, calendar year and residence. Given an initial cutaneous melanoma, there was a 10‐fold increased risk of developing a second cutaneous melanoma (95% confidence interval [CI] = 9.4–10.6). Persons with uveal melanoma went on to develop cutaneous melanoma 4.6 times (95% CI = 2.9–6.8) more often than the population at large. In contrast, persons with cutaneous melanoma were not subsequently diagnosed with uveal melanoma at an appreciably elevated rate (standardized incidence ratio [SIR] = 1.4; 95% CI = 0.5–3.0). While these data offer some support for the hypothesis that uveal and cutaneous melanomas have 1 or more etiologies in common, the lack of symmetry in the pattern of second uveal and second cutaneous melanomas remains unexplained. © 2002 Wiley‐Liss, Inc.
Chromosomal alterations in small cell lung cancer revealed by multicolour fluorescence in situ hybridization
Authors: Ashman J.N.E. , Brigham J. , Cowen M.E. , Bahia H. , Greenman J. , Lind M. , Cawkwell L. 
Published: October 2002

AbstractSmall cell lung cancer (SCLC) is a major cause of cancer related morbidity and mortality. Karyotypic studies have revealed numerous chromosomal aberrations in most SCLC however, classical G‐banding analysis is unable to fully characterise complex marker chromosomes. Recent developments in molecular cytogenetics now allow accurate identification of the chromosomal components of complicated rearrangements. We have applied the technique of multicolour fluorescence in situ hybridization (M‐FISH) in combination with comparative genomic hybridization (CGH) to the analysis of 5 SCLC cell lines and 1 primary tumour specimen to characterise the chromosomal abnormalities. CGH analysis identified many similarities between specimens, with frequent DNA copy number decreases on chromosomes 3p, 5q, 10, 16q, 17p and frequent gains on 3q, 1p, 1q and 14q. In contrast, M‐FISH analysis revealed a large number of structural abnormalities, with each specimen demonstrating an individual pattern of chromosomal translocations. Forty different translocations were identified with the vast majority (39) being unbalanced. Chromosome 5 was the most frequently rearranged chromosome (9 translocations) followed by chromosomes 2, 10 and 16 (6 translocations each). Further investigation of these frequently involved chromosomes is warranted to establish whether consistent break points are involved in these translocations, causing dysregulation of specific genes that are crucial for tumour progression and secondly to identify the affected genes. © 2002 Wiley‐Liss, Inc.
Mortality and incidence trends from esophagus cancer in selected geographic areas of China circa 1970–90
Authors: Ke Li 
Published: October 2002

AbstractChina was one of the countries with the highest esophagus cancer risk in the world during the 1970s. This report provides data on time trends of esophagus cancer incidence and mortality during the 1970s–90s in selected geographic areas of China. Information on newly diagnosed cancer cases and cancer deaths is based on data collected by local population‐based registries and Disease Surveillance Points (DSP). For the whole country, esophagus cancer mortality decreased slightly, 17.4 per 105 populations during 1990–92 in contrast to 18.8 per 105 populations in 1973–75. In the Linxian area, trends in the incidence and mortality rates for esophagus+gastric cardia cancer reversed over time; incidence rates increased significantly during 1959–72 but were decreased significantly on average −2.26% (95% Confidence Interval [CI]: −1.74, −2.77) and −1.10% (95% CI = −0.58, −1.62) per year for males and females, respectively, during 1972–97. In urban Shanghai, incidence trend for esophagus cancer decreased monotonically and significantly on average by −4.99% (95% CI = −4.28, −5.70) and −5.18% (95% CI = −4.99, −5.70) per year for males and females, respectively. In Nanao islet, esophagus+gastric cardia cancer mortality rates increased during 1970–82 but decreased slowly from 1982–99 (−0.96% per year; 95% CI = −0.14, −1.78). Our study indicates that incidence and mortality rates for esophagus or esophagus+gastric cardia cancer are now decreasing in China. The declines may be due to an unplanned success of prevention, such as changes in population dietary patterns and food preservation methods. © 2002 Wiley‐Liss, Inc.
Ganoderma lucidum extract induces cell cycle arrest and apoptosis in MCF‐7 human breast cancer cell
Authors: Hu Hongbo , Ahn Nam‐Shik , Yang Xinlin , Lee Yong‐Soon , Kang Kyung‐Sun 
Published: October 2002

AbstractAlthough the pharmacology and clinical application of water extracts of Ganoderma lucidum have been extensively documented, little is known regarding its alcohol extract. In the present study, the anti‐tumor effect of an alcohol extract of Ganoderma lucidum was investigated using MCF‐7 cells. We found that the alcohol extract of Ganoderma lucidum inhibited cell proliferation in a dose‐ and time‐dependent manner, which might be mediated through up‐regulation of p21/Waf1 and down‐regulation of cyclin D1. Furthermore, this compound can directly induce apoptosis in MCF‐7 cells, which might be mediated through up‐regulation of a pro‐apoptotic Bax protein and not by the immune system. Our findings suggest that there are multiple mechanisms underlying the anti‐tumor effects of Ganoderma lucidum. © 2002 Wiley‐Liss, Inc.
Impact of multiple HPV infection on response to treatment and survival in patients receiving radical radiotherapy for cervical cancer
Authors: Bachtiary Barbara , Obermair Andreas , Dreier Bettina , Birner Peter , Breitenecker Gerhard , Knocke Tomas‐Hendrik , Selzer Edgar , Pötter Richard 
Published: October 2002

AbstractTo obtain information on the incidence and the clinical significance of infection with various types of the human papillomavirus (HPV) in cancer of the uterine cervix, we retrospectively examined the HPV status of 106 patients who had received radical radiotherapy for cervical cancer stages IB to IIIB. DNA was extracted from formalin‐fixed, paraffin‐embedded biopsies and PCR was carried out to identify HPV types 16, 18, 31, 35, 33 and 45. To detect additional HPV types, consensus PCR products were cloned and sequenced. A catalyzed signal‐amplified colorimetric in situ hybridization was carried out in 84 of 106 specimens as a positive control. Response to therapy, progression‐free survival (PFS) and cervical cancer‐specific survival (CCSS) were the statistical endpoints. Survival analysis was carried out using univariate and multivariate analysis (Cox regression). Ninety‐six patients (90.6%) were HPV‐positive and 42/96 (43.7%) were positive for multiple HPV types. Eight patients had persistent disease after radiotherapy. From these 8 patients, 7 were infected with multiple HPV types and only 1 patient had an infection with a single HPV type. After a median follow up period of 50 months, patients with multiple HPV infection had a significantly shorter PFS and CCSS compared to those with single HPV infection (24.8% and 34.9% vs. 64% and 60.8%, Log rank, p < 0.01 and 0.04). In multivariate analysis, the presence of multiple HPV types (RR 1.9), node status (RR 2.3), tumor size (RR 3.2) and histologic type (RR 4.8) were independent prognostic factors of CCSS. Our results demonstrate that the presence of multiple HPV types is associated with poor response and with reduced survival in cervical cancer patients who receive radiotherapy as the primary treatment. © 2002 Wiley‐Liss, Inc.